FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Saitoh, H Sparrow, D Shiomi, T Nishimoto, T Mohun, T Dasso, M AF Saitoh, H Sparrow, D Shiomi, T Nishimoto, T Mohun, T Dasso, M TI The roles of UBC9 and SUMO-1 conjugation in nuclear transport. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892. NIMR,DIV DEV BIOL,LONDON,ENGLAND. KYUSHU UNIV,GRAD SCH MED SCI,DEPT MOL BIOL,FUKUOKA 812,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1997 VL 8 SU S BP 2481 EP 2481 PG 1 WC Cell Biology SC Cell Biology GA YF096 UT WOS:A1997YF09602475 ER PT J AU Love, DC Hanover, JA AF Love, DC Hanover, JA TI Distinct requirements for Rev nuclear import and export SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK,LAB CELL BIOCHEM & BIOL,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1997 VL 8 SU S BP 2486 EP 2486 PG 1 WC Cell Biology SC Cell Biology GA YF096 UT WOS:A1997YF09602480 ER PT J AU Sweitzer, TD Bennett, DD Hanover, JA AF Sweitzer, TD Bennett, DD Hanover, JA TI Tno roles for calcium in nuclear protein import. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK,LAB CELL BIOCHEM & BIOL,NIH,BETHESDA,MD 20892. MAYO CLIN & MAYO GRAD SCH MED,ROCHESTER,MN 55905. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1997 VL 8 SU S BP 2489 EP 2489 PG 1 WC Cell Biology SC Cell Biology GA YF096 UT WOS:A1997YF09602482 ER PT J AU Adya, N Liu, PP AF Adya, N Liu, PP TI Functional characterization of CBF beta-SMMHC, chimeric protein generated by chromosome inversion in AML. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCHGR,CLR LGT,NIH,BETHESDA,MD 20892. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1997 VL 8 SU S BP 2494 EP 2494 PG 1 WC Cell Biology SC Cell Biology GA YF096 UT WOS:A1997YF09602490 ER PT J AU Furumura, M Sakai, C Ollmann, M Potterf, SB Vieira, WD Barsh, GS Hearing, VJ AF Furumura, M Sakai, C Ollmann, M Potterf, SB Vieira, WD Barsh, GS Hearing, VJ TI Melanocyte genes modulated during the switch to produce pheomelanin as identified by differential display. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. STANFORD UNIV,MED CTR,SCH MED,HOWARD HUGHES MED INST,DEPT PEDIAT,STANFORD,CA 94305. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1997 VL 8 SU S BP 2498 EP 2498 PG 1 WC Cell Biology SC Cell Biology GA YF096 UT WOS:A1997YF09602492 ER PT J AU Rabinovitz, M AF Rabinovitz, M TI How cancer cells resist growth restriction by nutritional deprivation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1997 VL 8 SU S BP 2522 EP 2522 PG 1 WC Cell Biology SC Cell Biology GA YF096 UT WOS:A1997YF09602516 ER PT J AU Afonina, E Stauber, R Pavlakis, G AF Afonina, E Stauber, R Pavlakis, G TI Poly(A) binding protein (PABP1) shuttles between nucleus and cytoplasm: Possible nuclear role for cytoplasmic protein. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,HUMAN RETROVIRUS SECT,ABL BASIC RES PROGRAM,FCRDC,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1997 VL 8 SU S BP 2539 EP 2539 PG 1 WC Cell Biology SC Cell Biology GA YF096 UT WOS:A1997YF09602531 ER PT J AU Doren, S Landsberger, N Dwyer, N BlanchetteMackie, J Dean, J AF Doren, S Landsberger, N Dwyer, N BlanchetteMackie, J Dean, J TI Expression of zona pellucida proteins in Xenopus laevis oocytes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD 20892. NICHHD,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1997 VL 8 SU S BP 2548 EP 2548 PG 1 WC Cell Biology SC Cell Biology GA YF096 UT WOS:A1997YF09602541 ER PT J AU Morrison, RL Collett, ML Solarczyk, JM Nagashima, K AF Morrison, RL Collett, ML Solarczyk, JM Nagashima, K TI An ultrastructural analysis of pigment pattern formation in wild-type zebrafish SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 HOOD COLL,DEPT BIOL,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1997 VL 8 SU S BP 2557 EP 2557 PG 1 WC Cell Biology SC Cell Biology GA YF096 UT WOS:A1997YF09602551 ER PT J AU Chong, LD Latimer, E Friesel, R Daar, IO AF Chong, LD Latimer, E Friesel, R Daar, IO TI Tyrosine phosphorylation of an Eph transmembrane ligand alters its effect on cell adhesion in Xenopus laevis embryos SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD. AMER RED CROSS,HOLLAND LAB,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1997 VL 8 SU S BP 2569 EP 2569 PG 1 WC Cell Biology SC Cell Biology GA YF096 UT WOS:A1997YF09602563 ER PT J AU Normant, E Loh, YP AF Normant, E Loh, YP TI Carboxypeptidase E acts as a sorting receptor for routing proenkephalin and proinsulin but not chromogranin A to the regulated secretory pathway SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,LDN,CELLULAR NEUROBIOL SECT,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1997 VL 8 SU S BP 2615 EP 2615 PG 1 WC Cell Biology SC Cell Biology GA YF096 UT WOS:A1997YF09602606 ER PT J AU DellAngelica, EC Ooi, CE Bonifacino, JS AF DellAngelica, EC Ooi, CE Bonifacino, JS TI The adaptor protein complex AP-3 is associated with endosomes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,CBMB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1997 VL 8 SU S BP 2624 EP 2624 PG 1 WC Cell Biology SC Cell Biology GA YF096 UT WOS:A1997YF09602616 ER PT J AU Gastel, JA Zatz, M Klein, DC AF Gastel, JA Zatz, M Klein, DC TI cAMP-inhibited proteosomal degradation regulates melatonin production SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIMH,SECT BIOCHEM PHARMACOL,NIH,BETHESDA,MD 20892. NICHHD,SECT NEUROENDOCRINOL,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1997 VL 8 SU S BP 2632 EP 2632 PG 1 WC Cell Biology SC Cell Biology GA YF096 UT WOS:A1997YF09602625 ER PT J AU Zhang, Q Cox, D Tseng, CC Donaldson, JG Greenberg, S AF Zhang, Q Cox, D Tseng, CC Donaldson, JG Greenberg, S TI GTP hydrolysis by ARF6 is required for Fc receptor-mediated phagocytosis in macrophages. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. COLUMBIA UNIV COLL PHYS & SURG,DEPT MED,NEW YORK,NY 10032. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1997 VL 8 SU S BP 2642 EP 2642 PG 1 WC Cell Biology SC Cell Biology GA YF096 UT WOS:A1997YF09602633 ER PT J AU Slaga, TJ LeBoeuf, R Tennant, R AF Slaga, TJ LeBoeuf, R Tennant, R TI Tenth International Conference on Carcinogenesis and Risk Assessment: ''New approaches for assessing the carcinogenic potential of chemicals'' SO MOLECULAR CARCINOGENESIS LA English DT Editorial Material C1 PROCTER & GAMBLE CO,DIV HUMAN & ENVIRONM SAFETY,ROSS,OH. NIEHS,LAB ENVIRONM CARCINOGENESIS & MUTAGENESIS,RES TRIANGLE PK,NC 27709. RP Slaga, TJ (reprint author), UNIV TEXAS,MD ANDERSON CANC CTR,DIV SCI PK RES,SMITHVILLE,TX 78957, USA. NR 0 TC 0 Z9 0 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 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD NOV PY 1997 VL 20 IS 3 BP 261 EP 261 PG 1 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA YJ382 UT WOS:A1997YJ38200001 ER PT J AU Mitsumori, K Wakana, S Yamamoto, S Kodama, Y Yasuhara, K Nomura, T Hayashi, Y Maronpot, RR AF Mitsumori, K Wakana, S Yamamoto, S Kodama, Y Yasuhara, K Nomura, T Hayashi, Y Maronpot, RR TI Susceptibility of transgenic mice carrying human prototype c-Ha-ras gene in a short-term carcinogenicity study of vinyl carbamate and ras gene analyses of the induced tumors SO MOLECULAR CARCINOGENESIS LA English DT Article; Proceedings Paper CT 10th International Conference on Carcinogenesis and Risk Assessment - New Approaches for Assessing the Carcinogenic Potential of Chemicals CY DEC 04-07, 1996 CL AUSTIN, TX DE CB6F1-Tg Hras2 mouse; point mutation; murine Ki-ras; lung tumors; splenic hemangiosarcoma; forestomach tumor ID ETHYL CARBAMATE; LIVER-TUMORS; INDUCED LUNG; URETHANE; PROTOONCOGENE; METABOLITE; INDUCTION; MUTATIONS; EPOXIDE; DNA AB To determine if hemizygous transgenic mice carrying the human c-Ha-ras gene (CB6F1-Tg Hras2 mice (Hras2 mice)) are susceptible to the carcinogenic potential of known murine carcinogens, male and female Hras2 mice and their non-transgenic CB6F1 littermates (non-Tg mice) were each given a single intraperitoneal injection of 60 mg of vinyl carbamate (VC)/kg body weight or saline (vehicle control) and monitored for 16 wk without further treatment. At necropsy, grossly visible tumors were fixed for histopathologic diagnosis and, when of sufficient size, portions were frozen for subsequent molecular analysis. Nine of 31 male and nine of 29 female Hras2 mice treated with VC died within 16 wk as a result of lung tumor burden. at the termination of the study, lung tumors (alveolar-bronchiolar epithelial neoplasms and hemangiosarcomas) and focal alveolar-bronchiolar hyperplasias were present in both sexes of Hras2 and non-Tg mice treated with VC; there were significantly more proliferative lung lesions in Hras2 than non-Tg mice. Splenic hemangiosarcomas and squamous cell tumors of the forestomach were induced in male and female VC-treated Hras2 mice but not in VC-treated non-Tg mice. Polymerase chain reaction-single-strand conformation polymorphism analysis and DNA sequencing of the induced lung tumors revealed point mutations at codon 61 of the transgene in two of 29 lung tumors (one of 16 in males and one of 13 in females) from VC-treated Hras2 mice; no mutations in murine Ki-ras were found in these tumors. Point mutations at codons 12 and 61 of the murine Ki-ras gene were observed, however, in one of 10 and six of 10 lung tumors respectively from VC-treated non-Tg mice. These findings indicate that Hras2 mice are highly sensitive to pulmonary neoplasms and splenic and lung hemangiosarcomas after treatment with VC. The molecular analyses suggest that point mutations of the transgene and the murine Ki-ras gene do not play a major role in VC induction of pulmonary neoplasms in there transgenic mice. (C) 1997 Wiley-Liss, Inc. C1 CENT INST EXPT ANIM, KAWASAKI, KANAGAWA, JAPAN. KEIO UNIV, SCH MED, DEPT PHARMACOL, TOKYO 160, JAPAN. NATL INST HLTH SCI, DIV TOXICOL, TOKYO 158, JAPAN. KITASATO UNIV, DEPT PHARMACEUT SCI, TOKYO, JAPAN. NIEHS, LAB EXPT PATHOL, RES TRIANGLE PK, NC 27709 USA. RP Mitsumori, K (reprint author), NATL INST HLTH SCI, DIV PATHOL, 1-18-1 KAMIYOGA, TOKYO 158, JAPAN. NR 27 TC 42 Z9 42 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD NOV PY 1997 VL 20 IS 3 BP 298 EP 307 DI 10.1002/(SICI)1098-2744(199711)20:3<298::AID-MC6>3.0.CO;2-H PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA YJ382 UT WOS:A1997YJ38200006 PM 9397190 ER PT J AU Suh, DS Rechler, MM AF Suh, DS Rechler, MM TI Hepatocyte nuclear factor 1 and the glucocorticoid receptor synergistically activate transcription of the rat insulin-like growth factor binding protein-1 gene SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PHOSPHOENOLPYRUVATE CARBOXYKINASE GENE; FACTOR (IGF)-BINDING PROTEINS; STREPTOZOTOCIN-DIABETIC RATS; IGFBP-1 MESSENGER-RNA; FACTOR-I; IGF-I; PROMOTER ACTIVITY; HOMEODOMAIN PROTEINS; TRANSGENIC MICE; CELL-MIGRATION AB The insulin-like growth factor (IGF) binding proteins (IGFBPs) are a family of proteins that bind IGF-I and IGF-II and modulate their biological activities. IGFBP-1 is distinctive among the IGFBPs in its rapid regulation in response to metabolic and hormonal changes. The synthetic glucocorticoid, dexamethasone, increases IGFBP-1 mRNA abundance and gene transcription in rat liver and in H4-II-E rat hepatoma cells. A glucocorticoid response element (GRE) located at nucleotide (nt)-91/-77 is required for dexamethasone to stimulate rat IGFBP-1 promoter activity in transient transfection assays in H4-II-E cells. In addition to the GRE, three accessory regulatory sites [a putative hepatocyte nuclear factor-1 (HNF-1) site (nt-62/-50), an insulin-response element (nt-108/ -99), and an upstream site (nt-252/-236)] are involved in dexamethasone stimulation under some, but not all, circumstances. The present study begins to address the mechanism by which transcription factors bound to the putative HNF-1 site act synergistically with the glucocorticoid receptor (GR) bound to the GRE. In gel shift assays, HNF-1 alpha and HNF-1 beta in H4-II-E extracts bind to the palindromic HNF-1 site. Both half-sites are required. Overexpression of HNF-1 beta enhances dexamethasone-stimulated promoter activity. Both the HNF-1 site and the GRE must be intact for stimulation to occur. By contrast, overexpression of HNF-1 alpha does not enhance dexamethasone-stimulated promoter activity, although, as also observed with overexpression of HNF-1 beta, it inhibits basal promoter activity, Thus, the synergistic effects of HNF-1 beta and the on on dexamethasone-stimulated promoter activity require that they are bound to the HNF-1 site and the GRE, respectively, and may involve protein-protein interactions between the transcription factors, or between them and the basal transcription machinery or a steroid receptor coactivator. Synergy between the ubiquitously expressed GR and HNF-1, which is developmentally regulated and expressed in a limited number of tissues, provides a possible mechanism for tissue-and development-specific regulation of glucocorticoid action. C1 NIDDKD,GROWTH & DEV SECT,MOL & CELLULAR ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. NR 57 TC 30 Z9 30 U1 0 U2 3 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 NOV PY 1997 VL 11 IS 12 BP 1822 EP 1831 DI 10.1210/me.11.12.1822 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YD563 UT WOS:A1997YD56300008 PM 9369450 ER PT J AU Wang, RF AF Wang, RF TI Tumor antigens discovery: Perspectives for cancer therapy SO MOLECULAR MEDICINE LA English DT Review ID CYTOLYTIC T-LYMPHOCYTES; GENE-EXPRESSION PATTERNS; HUMAN DENDRITIC CELLS; BETA-CATENIN GENE; HUMAN-MELANOMA; INFILTRATING LYMPHOCYTES; METASTATIC MELANOMA; HLA-A2 MELANOMAS; BREAST-CANCER; DIFFERENTIATION ANTIGEN AB The adoptive transfer of cytotoxic T lymphocytes (CTLs) derived from tumor-infiltrating lymphocytes (TIL) along with interleukin 2 (IL-2) into autologous patients with cancer resulted in the objective regression of tumor, indicating that these CTLs recognized cancer rejection antigens on tumor cells. To understand the molecular basis of T cell-mediated antitumor immunity, several groups started to search for such tumor antigens in melanoma as well as in other types of cancers. This led to the subject I will review in this article. A number of tumor antigens were isolated by the use of cDNA expression systems and biochemical approaches. These tumor antigens could be classified into several categories: tissue-specific differentiation antigens, tumor-specific shared antigens, and tumor-specific unique antigens, However, the majority of tumor antigens identified to date are nonmutated, self proteins. This raises important questions regarding the mechanism of antitumor activity and autoimmune disease. The identification of human tumor rejection antigens provides new opportunities for the development of therapeutic strategies against cancer, This review will summarize the current status and progress toward identifying human tumor antigens and their potential applications to cancer treatment. RP Wang, RF (reprint author), NCI,NIH,BLDG 10,RM 2B42,BETHESDA,MD 20814, USA. NR 104 TC 16 Z9 19 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 1076-1551 J9 MOL MED JI Mol. Med. PD NOV PY 1997 VL 3 IS 11 BP 716 EP 731 PG 16 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA YH637 UT WOS:A1997YH63700002 PM 9407548 ER PT J AU Zhong, Z Connor, H Stachlewitz, RF VonFrankenberg, M Mason, RP Lemasters, JJ Thurman, RG AF Zhong, Z Connor, H Stachlewitz, RF VonFrankenberg, M Mason, RP Lemasters, JJ Thurman, RG TI Role of free radicals in primary nonfunction of marginal fatty grafts from rats treated acutely with ethanol SO MOLECULAR PHARMACOLOGY LA English DT Article ID ORTHOTOPIC LIVER-TRANSPLANTATION; LIPID-PEROXIDATION; HEPATIC ISCHEMIA; KUPFFER CELLS; ALCOHOL; INVIVO; INTOXICATION; GENERATION; INVITRO AB Acute treatment with one large dose of ethanol, which mimics binge drinking, causes marginal fatty liver and decreases survival significantly after liver transplantation in rats, yet mechanisms remain unclear. Therefore, we evaluated the possible role of free radicals in primary nonfunction caused by acute ethanol. Female donor rats were administered ethanol (5 g/kg orally) 20 hr before explantation, and grafts were stored in UW cold storage solution for 24-42 hr before implantation. Free radicals were trapped with alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone after transplantation, and adducts were detected using electron spin resonance spectrometry. Ethanol increased a carbon-centered radical adduct in bile similar to 2-fold and elevated serum lipid hydroperoxides similar to 4-fold. Ethanol also increased transaminase release 3.7-fold and decreased bile production by 55%. Catechin, a free radical scavenger, minimized the increase in free radicals, blunted transaminase release, and elevated bile production significantly, indicating that free radical production plays an important role in ethanol-induced fatty graft injury. GdCl3 (20 mg/kg intravenously), a selective Kupffer cell toxicant, largely blocked the increases in free radical and lipid hydroperoxide production caused by ethanol. In addition, ethanol nearly doubled white blood cell adhesion after transplantation, leading to increased superoxide production in fatty grafts. GdCl3 largely blocked leukocyte adhesion as well as superoxide production. Allopurinol, an inhibitor of xanthine oxidase, also diminished free radical production, blunted transaminase release, and improved bile production in fatty grafts significantly. Taken together, we conclude that free radical formation increases in ethanol-induced fatty grafts due mainly to activation of Kupffer cells and increased adhesion of white blood cells. Antioxidants can effectively block free radical formation and minimize injury to marginal fatty grafts caused by binge drinking. C1 UNIV N CAROLINA, DEPT PHARMACOL, CHAPEL HILL, NC 27599 USA. UNIV N CAROLINA, DEPT CELL BIOL & ANAT, CHAPEL HILL, NC 27599 USA. NIEHS, LAB PHARMACOL & CHEM, RES TRIANGLE PK, NC 27709 USA. FU NIAAA NIH HHS [AA09156] NR 43 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 1997 VL 52 IS 5 BP 912 EP 919 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YE870 UT WOS:A1997YE87000019 PM 9351983 ER PT J AU Higgins, JJ Pho, LT Nee, LE AF Higgins, JJ Pho, LT Nee, LE TI A gene (ETM) for essential tremor maps to chromosome 2p22-p25 SO MOVEMENT DISORDERS LA English DT Review DE linkage analysis; essential tremor; human chromosome 2p ID MULTILOCUS LINKAGE ANALYSIS AB We report the results of linkage analysis in a large American family of Czech descent with dominantly inherited ''pure'' essential tremor (ET) and genetic anticipation. Genetic loci on chromosome 2p22-p25 establish linkage to this region with a maximum LOD score (Z(max)) = 5.92 for the locus, D2S272. Obligate recombinant events place the ETM gene in a 15-cM candidate interval between the genetic loci D2S168 and D2S224. Repeat expansion detection analysis suggests that expanded CAG trinucleotide sequences are associated with ET. These findings will facilitate the search for an ETM gene and may further our understanding of the human motor system. RP Higgins, JJ (reprint author), NINCDS,CLIN NEUROGENET UNIT,MED NEUROL BRANCH,NIH,BLDG 10,ROOM 5N234,BETHESDA,MD 20892, USA. NR 31 TC 132 Z9 139 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD NOV PY 1997 VL 12 IS 6 BP 859 EP 864 DI 10.1002/mds.870120605 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA YF945 UT WOS:A1997YF94500004 PM 9399207 ER PT J AU Okinaka, RT Perez-Castro, AV Sena, A Laubscher, K Strniste, GF Park, MS Hernandez, R MacInnes, MA Kraemer, KH AF Okinaka, RT Perez-Castro, AV Sena, A Laubscher, K Strniste, GF Park, MS Hernandez, R MacInnes, MA Kraemer, KH TI Heritable genetic alterations in a xeroderma pigmentosum group G Cockayne syndrome pedigree SO MUTATION RESEARCH-DNA REPAIR LA English DT Article DE xeroderma pigmentosum; Cockayne Syndrome ID COMPLEMENTATION GROUP-G; NUCLEOTIDE EXCISION NUCLEASE; DNA-REPAIR DEFECT; IONIZING-RADIATION; MOLECULAR-BASIS; YEAST RAD2; CELLS; PATIENT; CDNA; AMPLIFICATION AB A search for genetic alterations within the XPG gene has been conducted on skin and blood cells cultured from a newly characterized xeroderma pigmentosum (XP) patient (XP20BE). This patient is the ninth known case that falls into the extremely rare XP complementation group G. Four genetic markers within the XPG gene (including two polymorphisms) demonstrated the Mendelian distribution of this gene from the parents to the patient and to an unaffected sibling. The patient (XP20BE) inherited a G to T transversion from his father in exon I of the XPG gene that resulted in the conversion of a glutamic acid at codon 11 to a termination codon. The patient also inherited an XP-G allele from his mother that produces an unstable or poorly expressed message. The cause of the latter defect is still uncertain. In addition to these alterations, XP20BE cDNA contained an mRNA species with a large splicing defect that encompassed a deletion from exon 1 to exon 14. This splicing defect, however, appears to be a naturally occurring low-frequency event that results from abnormal splicing that occurs between certain conserved non-consensus splicing signals within the human XPG gene. (C) 1997 Elsevier Science B.V. C1 Univ Calif Los Alamos Natl Lab, Div Life Sci, Los Alamos, NM 87545 USA. No New Mexico Coll, Dept Biol, Espanola, NM 87532 USA. NCI, Mol Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Okinaka, RT (reprint author), Univ Calif Los Alamos Natl Lab, Div Life Sci, LS-6,M888, Los Alamos, NM 87545 USA. FU Intramural NIH HHS [Z01 BC004517-31] NR 35 TC 26 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8777 J9 MUTAT RES-DNA REPAIR JI Mutat. Res.-DNA Repair PD NOV PY 1997 VL 385 IS 2 BP 107 EP 114 DI 10.1016/S0921-8777(97)00031-1 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA YQ499 UT WOS:000071393900003 PM 9447232 ER PT J AU Biesecker, LG AF Biesecker, LG TI Strike three for GLI3 SO NATURE GENETICS LA English DT Editorial Material ID MULTIPLE RP Biesecker, LG (reprint author), NATL HUMAN GENOME RES INST,LAB GENET DIS RES,NIH,BETHESDA,MD, USA. NR 11 TC 71 Z9 71 U1 0 U2 0 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 NOV PY 1997 VL 17 IS 3 BP 259 EP 260 DI 10.1038/ng1197-259 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA YD667 UT WOS:A1997YD66700007 PM 9354780 ER PT J AU Kakuta, Y Pedersen, LG Carter, CW Negishi, M Pedersen, LC AF Kakuta, Y Pedersen, LG Carter, CW Negishi, M Pedersen, LC TI Crystal structure of estrogen sulphotransferase SO NATURE STRUCTURAL BIOLOGY LA English DT Letter ID MOLECULAR CHARACTERIZATION; STEROID SULFOTRANSFERASES; REFINED STRUCTURE; ESCHERICHIA-COLI; EXPRESSION; BINDING; KINASE; SITE; RESOLUTION; DYNAMICS AB The structure of estrogen sulphotransferase has been solved in the presence of inactive cofactor PAP and substrate 17 beta-estradiol, This structure reveals structural similarities between cytosolic sulphotransferases and nucleotide kinases. C1 NIEHS,PHARMACOGENET SECT,REPROD & DEV TOXICOL LAB,NIH,RES TRIANGLE PK,NC 27709. NIEHS,LAB QUANTITAT & COMPUTAT BIOL,NIH,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,DEPT BIOCHEM & BIOPHYS,CHAPEL HILL,NC 27514. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 NR 33 TC 211 Z9 215 U1 0 U2 10 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 NOV PY 1997 VL 4 IS 11 BP 904 EP 908 DI 10.1038/nsb1197-904 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA YE159 UT WOS:A1997YE15900012 PM 9360604 ER PT J AU Kunko, PM Loeloff, RJ Izenwasser, S AF Kunko, PM Loeloff, RJ Izenwasser, S TI Chronic administration of the selective dopamine uptake inhibitor GBR 12909, but not cocaine, produces marked decreases in dopamine transporter density SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Article DE dopamine transporters; GBR 12909; cocaine; uptake inhibitors; caudate putamen; nucleus accumbens; dopamine uptake; continuous infusions ID NUCLEUS-ACCUMBENS; RAT STRIATUM; LIGAND-BINDING; UPTAKE SITES; NEURONAL CARRIER; UPTAKE COMPLEX; MESSENGER-RNA; GBR-12909; BRAIN; EXPRESSION AB The chronic continuous infusion of cocaine produces partial behavioral tolerance to cocaine and tolerance to the inhibition of dopamine uptake by cocaine, without changing dopamine transporter binding. In order to examine more closely the dopaminergic contribution to this effect, the selective dopamine uptake inhibitor GBR 12909 (30 mg/kg/day), cocaine (50 mg/kg/day), or vehicle, were continuously infused via osmotic minipump, and their effects on the dopamine transporter ex amined. Drug and vehicle pumps were implanted into male Sprague-Dawley rats and removed after seven days. [H-3]WIN 35,428 binding and [H-3]dopamine uptake were measured in caudate putamen and nucleus accumbens at varying intervals after pump removal. The B-max for [H-3]MN 35,428 binding was decreased by approximately 75% in the caudate putamen and by 40% in the nucleus accumbens of GBR 12909-treated rats both 1 and 4 days after pump removal, and was still significantly decreased after 10 days, but had returned to normal by 20 days post-treatment. In contrast, cocaine did not significantly alter [H-3]WIN 35,428 binding. GBR 12909 produced both tolerance to the inhibition of [H-3]dopamine uptake by cocaine, and a decrease in total uptake of dopamine, in the caudate putamen, with no change in the nucleus accumbens. The persistent reduction of [H-3]WIN 35,428 binding following continuous GBR 12909 does not appear to result from residual drug binding. These findings suggest that GBR 12909 and cocaine may bind to and regulate the dopamine transporter in different ways. C1 NIDA,PSYCHOBIOL SECT,DIV INTRAMURAL RES,NIH,BALTIMORE,MD 21224. RI Izenwasser, Sari/G-9193-2012 NR 49 TC 31 Z9 31 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD NOV PY 1997 VL 356 IS 5 BP 562 EP 569 DI 10.1007/PL00005091 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YF845 UT WOS:A1997YF84500005 PM 9402035 ER PT J AU Gibson, GE Vestling, M Zhang, H Szolosi, S Alkon, D Lannfelt, L Gandy, S Cowburn, RF AF Gibson, GE Vestling, M Zhang, H Szolosi, S Alkon, D Lannfelt, L Gandy, S Cowburn, RF TI Abnormalities in Alzheimer's disease fibroblasts bearing the APP670/671 mutation SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's disease; calcium; fibroblasts; amyloid precursor protein; alpha-ketoglutarate dehydrogenase; bombesin; bradykinin; signal transduction ID AMYLOID PRECURSOR PROTEIN; CULTURED SKIN FIBROBLASTS; KETOGLUTARATE DEHYDROGENASE COMPLEX; BETA-PROTEIN; KINASE-C; AMINOGLYCOSIDE ANTIBIOTICS; SWEDISH FAMILY; FREE-RADICALS; CALCIUM; APP AB Abnormalities in cultured fibroblasts from familial Alzheimer's Disease (FAD) cases uniquely enable the determination of how gene defects alter cell biology in living tissue from affected individuals. The current study focused on measures of calcium regulation and oxidative metabolism in fibroblast lines from controls and FAD individuals with the Swedish APP670/671 mutation. Bombesin-induced elevations in calcium in APP670/671 mutation-bearing lines were reduced by 40% (p < 0.05), a striking contrast to the 100% increase seen in sporadic AD and presenilin-1 (PS1) mutation-bearing cells in previously published studies. The APP670/671 mutation-bearing lines did not exhibit the exaggerated 4-bromo-A23187 releasable pool of calcium following 10 nM bradykinin, the enhanced sensitivity of calcium stores to low concentrations of bradykinin, nor the reduced activity of alpha-ketoglutarate dehydrogenase previously reported in cells from sporadic AD and mutant PS1 FAD. Thus, an altered regulation of internal calcium stores is common to all AD lines, but the calcium pool affected and the polarity of the alteration varies, apparently in association with particular gene mutations. Comparison of signal transduction in cell lines from multiple, genetically characterized AD families will allow testing of the hypothesis that these various pathogenic FAD abnormalities that lend to AD converge at the level of abnormal signal transduction. (C) 1997 Elsevier Science Inc. C1 Cornell Univ, Coll Med, Burke Med Res Inst, White Plains, NY 10605 USA. Karolinska Inst, Novum, Dept Clin Neurosci & Family Med, KFC,Geriatr Med Sect, S-14186 Huddinge, Sweden. NINDS, Bethesda, MD 20892 USA. Cornell Univ, Med Ctr, Coll Med, New York, NY 10021 USA. RP Gibson, GE (reprint author), Cornell Univ, Coll Med, Burke Med Res Inst, 785 Mamaroneck Ave, White Plains, NY 10605 USA. EM ggibson@med.cornell.edu FU NIA NIH HHS [AG09464, AG11921, AG13780] NR 46 TC 39 Z9 40 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD NOV-DEC PY 1997 VL 18 IS 6 BP 573 EP 580 DI 10.1016/S0197-4580(97)00149-8 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA YR432 UT WOS:000071494700002 PM 9461055 ER PT J AU Brining, SK AF Brining, SK TI Predicting the in vitro toxicity of synthetic beta-amyloid (1-40) SO NEUROBIOLOGY OF AGING LA English DT Article DE beta-amyloid toxicity; Congo red; Alzheimer's disease; peptide conformation ID ALZHEIMERS-DISEASE; CONGO RED; SECONDARY STRUCTURE; PRION PROTEIN; PC12 CELLS; PRP ACCUMULATION; CONFORMATIONAL TRANSITIONS; POSSIBLE MECHANISM; SENILE PLAQUES; PEPTIDE AB The in vitro toxicity of synthetic beta-amyloid (beta A4) is variable and unpredictable, limiting its use as a research tool. This study describes a method using Congo red (CR) to predict the in vitro toxicity of beta A4 solutions. Histopathologically, CR is used to stain the neuritic, beta A4-containing plaques, one of the hallmarks of Alzheimer's disease. In this study, synthetic beta A4 solutions were incubated with CR at a molar ratio of 1.0:2.5. The solutions were centrifuged and the absorbance of the supernatants were measured. Predictions of nontoxicity correlated with absorbance readings near zero. Toxicity was evaluated relative to control cells (vehicle only), using a hemocytometer to count PC-12 cells that excluded trypan blue. The positive predictive value of the test was 78% and the negative predictive value was 100%. To use this test, the toxic concentration(s) of beta A4 must first be established empirically. Then, the CR test can be used to evaluate the potential toxicity of beta A4 solutions ar similar concentrations. Thus, this test can be used under a variety of laboratory circumstances. (C) 1997 Elsevier Science Inc. C1 NIA, NIH, Bethesda, MD 20892 USA. RP Brining, SK (reprint author), NIA, NIH, 10 Center Dr,MSC 1582,Bldg 10,Room 6C-103, Bethesda, MD 20892 USA. EM skb@helix.nih.gov NR 54 TC 20 Z9 20 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD NOV-DEC PY 1997 VL 18 IS 6 BP 581 EP 589 DI 10.1016/S0197-4580(97)00153-X PG 9 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA YR432 UT WOS:000071494700003 PM 9461056 ER PT J AU Gottfried, JA Mayer, SA Shungu, DC Chang, Y Duyn, JH AF Gottfried, JA Mayer, SA Shungu, DC Chang, Y Duyn, JH TI Delayed posthypoxic demyelination - Association with arylsulfatase A deficiency and lactic acidosis on proton MR spectroscopy SO NEUROLOGY LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; A PSEUDODEFICIENCY; BRAIN AB Delayed demyelination is a rare and poorly understood complication of hypoxic brain injury. A previous case report has suggested an association with mild-to-moderate deficiency of arylsulfatase A. We describe a 36-year-old man who recovered completely from an episode of hypoxia related to drug overdose, and 2 weeks later progressed from a confusional state to deep coma. MRI showed diffuse white matter signal changes, and brain biopsy demonstrated a noninflammatory demyelinating process. Proton magnetic resonance spectroscopy revealed elevated choline and lactate and reduced N-acetyl aspartate signal in the affected white matter, consistent with demyelination and a shift to anaerobic metabolism. Arylsulfatase A activity from peripheral leukocytes was approximately 50% of normal, consistent with a ''pseudodeficiency'' phenotype. These findings confirm the hypothesis that relative arylsulfatase A deficiency predisposes susceptible individuals to delayed posthypoxic leukoencephalopathy and implicates lactic acidosis in the pathogenesis of this disorder. C1 NYU, MED CTR, DEPT PHYSIOL, NEW YORK, NY 10016 USA. NYU, MED CTR, DEPT NEUROSCI, NEW YORK, NY 10016 USA. COLUMBIA PRESBYTERIAN MED CTR, DEPT NEUROL, NEW YORK, NY 10032 USA. COLUMBIA PRESBYTERIAN MED CTR, DEPT RADIOL, NEW YORK, NY 10032 USA. COLUMBIA PRESBYTERIAN MED CTR, DEPT PATHOL, NEW YORK, NY 10032 USA. NIH, LAB DIAGNOST RADIOL RES, BETHESDA, MD 20892 USA. RI Duyn, Jozef/F-2483-2010; Chang, Yuan/F-4146-2011; OI Shungu, Dikoma/0000-0001-9452-2245 NR 20 TC 35 Z9 37 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 1997 VL 49 IS 5 BP 1400 EP 1404 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA YF844 UT WOS:A1997YF84400040 PM 9371929 ER PT J AU Brodsky, M Jay, W Johnson, P Lamey, D Cain, S Wheeler, B Lam, B Nazarian, S Nichols, J Buckholts, A Ford, R OrengoNania, S McCrary, J Rolak, L Slight, B Chung, S Gross, R Howard, A Lai, E Frady, P Katz, B Foltos, C Ambrosio, T Cruz, T Hawker, N Swahn, T Barsness, D ChristKuhn, J Gaffney, M Loey, N Buckley, E Anderson, M Valentine, G Massey, E Pollock, S Radtke, R Duncan, L Patterson, D Guy, J Zam, S Burke, R Francis, A Shamis, D Chrousos, G Burt, E Kattah, J Goodwin, J Aslan, R Lindeman, M Sullivan, L Bobak, P Thompson, S Corbett, J Musser, C Donahue, S Farrell, T JohnstonMcNussen, P Kardon, R Mishra, A Neahring, R Wall, M Fountain, C Savino, P Ward, S Devlin, N Bosley, T Cantor, C McCloskey, L Sergott, R Davis, A Edwards, R Morton, D Miller, N Medura, M Putzulo, C Buchholz, D Reich, S Repka, T West, L Trobe, J Castillo, R Caudill, C Cornblath, W Michael, B Kaufman, D Holliday, S Bickert, S Froehlich, J Kokinakis, J Eggenberger, E Myint, S Barris, M Rosick, E Kupersmith, M Langer, R Addessi, A Weinman, J Fromer, E Wahba, S Shults, W Boly, L Beardsley, C Dreyer, R Herndon, R Wilson, R Arends, J Beaudry, T Smith, C Kuder, D MacKinnon, G Smith, S Sparenburg, J Tran, E Beck, R Moke, P Zajac, L Blair, RC Lester, L Gillespie, H Miskala, P Jureidini, F Kahn, D Mhamdi, M Keltner, J Johnson, C Spurr, J Shapiro, L Hakim, H Claunch, D Beam, D Owensby, D Anderson, MA Cleary, P Paty, D Mowery, R Everett, D AF Brodsky, M Jay, W Johnson, P Lamey, D Cain, S Wheeler, B Lam, B Nazarian, S Nichols, J Buckholts, A Ford, R OrengoNania, S McCrary, J Rolak, L Slight, B Chung, S Gross, R Howard, A Lai, E Frady, P Katz, B Foltos, C Ambrosio, T Cruz, T Hawker, N Swahn, T Barsness, D ChristKuhn, J Gaffney, M Loey, N Buckley, E Anderson, M Valentine, G Massey, E Pollock, S Radtke, R Duncan, L Patterson, D Guy, J Zam, S Burke, R Francis, A Shamis, D Chrousos, G Burt, E Kattah, J Goodwin, J Aslan, R Lindeman, M Sullivan, L Bobak, P Thompson, S Corbett, J Musser, C Donahue, S Farrell, T JohnstonMcNussen, P Kardon, R Mishra, A Neahring, R Wall, M Fountain, C Savino, P Ward, S Devlin, N Bosley, T Cantor, C McCloskey, L Sergott, R Davis, A Edwards, R Morton, D Miller, N Medura, M Putzulo, C Buchholz, D Reich, S Repka, T West, L Trobe, J Castillo, R Caudill, C Cornblath, W Michael, B Kaufman, D Holliday, S Bickert, S Froehlich, J Kokinakis, J Eggenberger, E Myint, S Barris, M Rosick, E Kupersmith, M Langer, R Addessi, A Weinman, J Fromer, E Wahba, S Shults, W Boly, L Beardsley, C Dreyer, R Herndon, R Wilson, R Arends, J Beaudry, T Smith, C Kuder, D MacKinnon, G Smith, S Sparenburg, J Tran, E Beck, R Moke, P Zajac, L Blair, RC Lester, L Gillespie, H Miskala, P Jureidini, F Kahn, D Mhamdi, M Keltner, J Johnson, C Spurr, J Shapiro, L Hakim, H Claunch, D Beam, D Owensby, D Anderson, MA Cleary, P Paty, D Mowery, R Everett, D TI The 5-year risk of MS after optic neuritis - Experience of the optic neuritis treatment trial SO NEUROLOGY LA English DT Article ID MULTIPLE-SCLEROSIS; FOLLOW-UP; BRAIN; CORTICOSTEROIDS; MODELS AB The objective of our study was to assess the 5-year risk of and prognostic factors for the development of clinically definite multiple sclerosis (CDMS) following optic neuritis. In a prospective cohort study design, 388 patients, who did not have probable or definite MS at study entry enrolled in the Optic Neuritis Treatment Trial between 1988 and 1991, and were followed for the development of CDMS. The 5-year cumulative probability of CDMS nias 30% and did not differ by treatment group. Neurologic impairment in the patients who developed CDMS was generally mild. Brain MRI performed at study entry was a strong predictor of CDMS, with the 5-year risk of CDMS ranging from 16% in the 202 patients with no MRI lesions to 51% in the 89 patients with three or more MRI lesions. Independent of brain MRI, the presence of prior nonspecific neurologic symptoms was also predictive of the development of CDMS. Lack of pain, the presence of optic disk swelling, and mild visual acuity loss were features of the optic neuritis associated with a low risk of CDMS among the 189 patients who had no brain MRI lesions and no history of neurologic symptoms or optic neuritis in the fellow eye. The 5-year risk of CDMS following optic neuritis is highly dependent an the number of lesions present on brain MRI. However, even a normal brain MRI does not preclude the development of GDMS. In these patients with no brain MRI lesions, certain clinical features identify a subgroup with a particularly low 5-year risk of CDMS. C1 UNIV ARKANSAS,LITTLE ROCK,AR 72204. BAYLOR COLL MED,HOUSTON,TX 77030. CALIF PACIFIC MED CTR,SAN FRANCISCO,CA. DUKE UNIV,DURHAM,NC 27706. UNIV FLORIDA,GAINESVILLE,FL. GEORGETOWN UNIV,WASHINGTON,DC. UNIV ILLINOIS,CHICAGO,IL 60680. UNIV IOWA,IOWA CITY,IA 52242. THOMAS JEFFERSON UNIV,WILLS EYE HOSP,PHILADELPHIA,PA 19107. JOHNS HOPKINS UNIV,BALTIMORE,MD. UNIV MICHIGAN,ANN ARBOR,MI 48109. MICHIGAN STATE UNIV,E LANSING,MI 48824. NYU,NEW YORK,NY. DEVERS EYE INST,PORTLAND,OR. SWEDISH MED CTR,SEATTLE,WA. UNIV CALIF DAVIS,DAVIS,CA. NEI,BETHESDA,MD 20892. RP Brodsky, M (reprint author), JAEB CTR HLTH RES,OPT NEURITIS STUDY GRP,3010 E 138TH AVE,SUITE 9,TAMPA,FL 33613, USA. NR 29 TC 233 Z9 235 U1 1 U2 10 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 1997 VL 49 IS 5 BP 1404 EP 1413 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA YF844 UT WOS:A1997YF84400041 ER PT J AU Hallenbeck, JM AF Hallenbeck, JM TI Cytokines, macrophages, and leukocytes in brain ischemia SO NEUROLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; FOCAL CEREBRAL-ISCHEMIA; ENDOTHELIAL-CELLS; FACTOR-ALPHA; RAT; INTERLEUKIN-1; INFLAMMATION; EXPRESSION; INJURY RP Hallenbeck, JM (reprint author), NINCDS,STROKE BRANCH,NIH,36 CONVENT DR,MSC 4128,BLDG 36,ROOM 4A03,BETHESDA,MD 20897, USA. NR 17 TC 22 Z9 22 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 1997 VL 49 IS 5 SU 4 BP S5 EP S9 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA YG393 UT WOS:A1997YG39300003 PM 9371141 ER PT J AU Chen, SM Wang, QL Nie, ZQ Sun, H Lennon, G Copeland, NG Gilbert, DJ Jenkins, NA Zack, DJ AF Chen, SM Wang, QL Nie, ZQ Sun, H Lennon, G Copeland, NG Gilbert, DJ Jenkins, NA Zack, DJ TI Crx, a novel Otx-like paired-homeodomain protein, binds to and transactivates photoreceptor cell-specific genes SO NEURON LA English DT Article ID ROD RETINAL DYSTROPHY; CIS-ACTING ELEMENT; TISSUE-SPECIFIC EXPRESSION; TRANSCRIPTION FACTOR NRL; HOMEO DOMAIN PROTEIN; RAT OPSIN PROMOTER; TRANSGENIC MICE; UPSTREAM REGION; CHROMOSOME 19Q; MOUSE RETINA AB The otd/Otx gene family encodes paired-like homeodomain proteins that are involved in the regulation of anterior head structure and sensory organ development. Using the yeast one-hybrid screen with a bait containing the Ret 4 site from the bovine rhodopsin promoter, we have cloned a new member of the family, Crx (Cone rod homeobox). Crx encodes a 299 amino acid residue protein with a paired-like homeodomain near its N terminus. In the adult, it is expressed predominantly in photoreceptors and pinealocytes. In the developing mouse retina, it is expressed by embryonic day 12.5 (E12.5). Recombinant Crx binds in vitro not only to the Ret 4 site but also to the Ret 1 and BAT-1 sites. In transient transfection studies, Crx transactivates rhodopsin promoter-reporter constructs. Its activity is synergistic with that of Nr1. Crx also binds to and transactivates the genes for several other photoreceptor cell-specific proteins (interphotoreceptor retinoid-binding protein, beta-phosphodiesterase, and arrestin). Human Crx maps to chromosome 19q13.3, the site of a cone rod dystrophy (CORDII). These studies implicate Crx as a potentially important regulator of photoreceptor cell development and gene expression and also identify it as a candidate gene for CORDII and other retinal diseases. C1 JOHNS HOPKINS UNIV,SCH MED,WILMER INST,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,DEPT MOL BIOL & GENET,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21287. LAWRENCE LIVERMORE NATL LAB,CTR HUMAN GENOME,LIVERMORE,CA 94550. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. OI Zack, Don/0000-0002-7966-1973 FU NEI NIH HHS [EY01765, EY09769, F32 EY006614] NR 77 TC 479 Z9 483 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD NOV PY 1997 VL 19 IS 5 BP 1017 EP 1030 DI 10.1016/S0896-6273(00)80394-3 PG 14 WC Neurosciences SC Neurosciences & Neurology GA YH594 UT WOS:A1997YH59400010 PM 9390516 ER PT J AU Siarey, RJ Stoll, J Rapoport, SI Galdzicki, Z AF Siarey, RJ Stoll, J Rapoport, SI Galdzicki, Z TI Altered long-term potentiation in the young and old Ts65Dn mouse, a model for Down Syndrome SO NEUROPHARMACOLOGY LA English DT Article DE Down Syndrome; trisomy; Ts65Dn; long-term potentiation (LTP); hippocampus; mental retardation; learning ID ROOT GANGLION NEURONS; TRISOMY-16 MOUSE; BEHAVIORAL-ASSESSMENT; MUTANT MICE; HIPPOCAMPUS; CHROMOSOME-21; ABNORMALITIES; MYOINOSITOL; MUTATION; CURRENTS AB We investigated the phenomenon of long-term potentiation (LTP) in a genetic model of Down Syndrome, the segmental trisomy mouse (Ts65Dn). Ts65Dn mice survive to adulthood and have an extra chromosome that contains a segment of chromosome 16 homologous to human chromosome 21. In this study, field excitatory postsynaptic potentials (fEPSP) were recorded from the CA1 area of in vitro hippocampal slices from diploid and Ts65Dn mice, and LTP was induced by a single tetanizing pulse train (1 sec in duration) at 100 Hz. The hippocampus from both young (2 months) and older (9 months) Ts65Dn mice had a reduced LTP over a period of 60 min compared with LTP in age-matched controls. This finding may explain the reported behavioral and learning impairments in Ts65Dn mice; it suggests that this mouse model can be used to study the role of altered synaptic plasticity in mental retardation of Down Syndrome. Published by Elsevier Science Ltd. C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. Texas Tech Univ, Ctr Hlth, Sch Pharm, Amarillo, TX 79106 USA. RP Galdzicki, Z (reprint author), NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. EM zyga@helix.nih.gov NR 35 TC 152 Z9 152 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD NOV-DEC PY 1997 VL 36 IS 11-12 BP 1549 EP 1554 DI 10.1016/S0028-3908(97)00157-3 PG 6 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA YZ387 UT WOS:000072249300009 PM 9517425 ER PT J AU Dar, DE Zinder, O AF Dar, DE Zinder, O TI Short term effect of steroids on catecholamine secretion from bovine adrenal medulla chromaffin cells SO NEUROPHARMACOLOGY LA English DT Article DE catecholamines; secretion; steroids; progesterone; acetylcholine; nicotine ID RECEPTOR; MODULATION; GLUCOCORTICOIDS AB Bovine chromaffin cells were used to examine neuronal modulation, as their function is similar to sympathetic post-ganglionic neurons. The effect of steroids on evoked catecholamine secretion from primary culture of bovine adrenal medullary cells was investigated. A wide range of progestins, androgens and estrogens was found to have a significant effect on catecholamine secretion induced by the natural neurotransmitter acetylcholine (ACh). The androgens (especially androstandione and androsterone), as a class were the most effective in inhibition of stimulated secretion, while the estrogens had little, to no, effect. Among all steroids tested, progesterone had the most significant effect, other progestins were less potent. Progesterone inhibited catecholamine secretion evoked by ACh, nicotine and oxotremorine-M in a dose-dependent manner with similar IC50 values in the mu M range. It also blocked the secretion evoked by high potassium concentration (59 nM) or veratradine (100 mu M), but no effect was seen on the secretion evoked by the calcium ionophore A-23187 (10 mu M). Progesterone inhibition of ACh or oxotremorine-M stimulation was immediate and sustained. These results suggest that progesterone and other steroids might have a membrane effect probably acting through blockade of calcium influx necessary for the secretory response. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Rambam Med Ctr, Dept Clin Biochem, IL-31096 Haifa, Israel. Technion Israel Inst Technol, Bruce Rappaport Fac Med, IL-31096 Haifa, Israel. RP Dar, DE (reprint author), NIDA, Mol Neurobiol Branch, Div Intramural Res, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ddar@irp.nida.nih.gov NR 23 TC 24 Z9 25 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD NOV-DEC PY 1997 VL 36 IS 11-12 BP 1783 EP 1788 DI 10.1016/S0028-3908(97)00150-0 PG 6 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA YZ387 UT WOS:000072249300036 PM 9517452 ER PT J AU Lane, RD Reiman, EM Bradley, MM Lang, PJ Ahern, GL Davidson, RJ Schwartz, GE AF Lane, RD Reiman, EM Bradley, MM Lang, PJ Ahern, GL Davidson, RJ Schwartz, GE TI Neuroanatomical correlates of pleasant and unpleasant emotion SO NEUROPSYCHOLOGIA LA English DT Article DE emotion; PET; cerebral blood flow; thalamus; prefrontal cortex; amygdala ID HUMAN AMYGDALA; FACIAL EXPRESSIONS; CORTEX; ATTENTION; STARTLE; ANXIETY; FEAR AB Substantial evidence suggests that a key distinction in the classification of human emotion is that between an appetitive motivational system associated with positive or pleasant emotion and an aversive motivational system associated with negative or unpleasant emotion. To explore the neural substrates of these two systems, 12 healthy women viewed sets of pictures previously demonstrated to elicit pleasant, unpleasant and neutral emotion, while positron emission tomographic (PET) measurements of regional cerebral blood flow were obtained. Pleasant and unpleasant emotions were each distinguished from neutral emotion conditions by significantly increased cerebral blood flow in the vicinity of the medial prefrontal cortex (Brodmann's area 9), thalamus, hypothalamus and midbrain (P < 0.005). Unpleasant was distinguished from neutral or pleasant emotion by activation of the bilateral occipito temporal cortex and cerebellum, and left parahippocampal gyrus, hippocampus and amygdala (P < 0.005). Pleasant was also distinguished from neutral but not unpleasant emotion by activation of the head of the left caudate nucleus (P < 0.005). These findings are consistent with those from other recent PET studies of human emotion and demonstrate that there are both common and unique components of the neural networks mediating pleasant and unpleasant emotion in healthy women. (C) 1997 Elsevier Science Ltd. C1 UNIV ARIZONA,DEPT PSYCHOL,TUCSON,AZ 85721. UNIV ARIZONA,DEPT NEUROL,TUCSON,AZ. SAMARITAN PET CTR,PHOENIX,AZ. UNIV FLORIDA,NIMH,CTR STUDY EMOT & ATTENT,GAINESVILLE,FL. UNIV WISCONSIN,DEPT PSYCHIAT,MADISON,WI 53706. UNIV WISCONSIN,DEPT PSYCHOL,MADISON,WI 53706. RP Lane, RD (reprint author), UNIV ARIZONA,DEPT PSYCHIAT,POB 245002,TUCSON,AZ 85724, USA. RI Frank, David/E-8213-2012 FU NIMH NIH HHS [MH-00972, MH-00875] NR 53 TC 558 Z9 569 U1 18 U2 51 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD NOV PY 1997 VL 35 IS 11 BP 1437 EP 1444 DI 10.1016/S0028-3932(97)00070-5 PG 8 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA YA308 UT WOS:A1997YA30800002 PM 9352521 ER PT J AU Mienville, JM Barker, JL AF Mienville, JM Barker, JL TI Potassium current expression during prenatal corticogenesis in the rat SO NEUROSCIENCE LA English DT Article DE potassium current; embryonic development; brain slice; patch-clamp; ion channel; Cajal-Retzius cell ID XENOPUS SPINAL NEURONS; K+ CURRENTS; POSTNATAL-DEVELOPMENT; IONIC CURRENTS; PATCH-CLAMP; SYMPATHETIC NEURONS; CILIARY GANGLION; CHANNELS; DIFFERENTIATION; CELLS AB Using in situ patch-clamp techniques, we have studied K current expression in rat telencephalon from embryonic day 12 to 21. For cells recorded in the ventricular zone, the K current consisted of a delayed rectifier and a large-conductance calcium-activated component, and displayed little variation from embryonic day 12 to 21. Cells recorded in pial regions could be separated into two classes: radially oriented, putatively migrating cells, and cells tangentially oriented in layer I, which were assumed to be Cajal-Retzius cells. When using a voltage-clamp protocol that included a prepulse to -120 mV, Cajal-Retzius cells displayed a larger density of total K current than radial cells, and both types revealed an inactivating component (I-A). The proportion of this component increased from embryonic day 18 to 21 in both cell types, although the amplitude of total K current, in the respective cell type, did not vary. This suggested a concomitant decrease in delayed rectifier current, which was verified directly with an appropriate protocol. The activation rate of the delayed rectifier current was slower for ventricular zone cells than for radial or Cajal-Retzius cells. I-A was studied in Cajal-Retzius cells and displayed a strikingly negative (similar to -100 mV) voltage of half-maximal steady-state inactivation. Tetraethylammonium ions only blocked the non-inactivating component(s) of K current whereas 4-aminopyridine appeared to decrease both inactivating and non-inactivating components. The quantitative changes in K current expression are likely to underlie the overall increase in excitability of differentiating cells. On the other hand, the observation of qualitative differences among channel properties opens an interesting area of investigation into their physiological significance. (C) 1997 IBRO. Published by Elsevier Science Ltd. C1 NINCDS,NEUROPHYSIOL LAB,NIH,BETHESDA,MD 20892. NR 43 TC 20 Z9 20 U1 0 U2 0 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 NOV PY 1997 VL 81 IS 1 BP 163 EP 172 DI 10.1016/S0306-4522(97)00171-1 PG 10 WC Neurosciences SC Neurosciences & Neurology GA XU143 UT WOS:A1997XU14300015 PM 9300409 ER PT J AU McCann, UD Lowe, KA Ricaurte, GA AF McCann, UD Lowe, KA Ricaurte, GA TI Long-lasting effects of recreational drugs of abuse on the central nervous system SO NEUROSCIENTIST LA English DT Review DE drug abuse; long-term effects; CNS; amphetamines; serotonin; neurotoxicity ID CENTRAL SEROTONERGIC NEURONS; NEONATAL 6-HYDROXYDOPAMINE TREATMENT; VESICULAR MONOAMINE TRANSPORTER; CENTRAL NORADRENALINE NEURONS; RAT NUCLEUS-ACCUMBENS; CHRONIC COCAINE USERS; DOPAMINE TRANSPORTER; ECSTASY ABUSE; 3,4-METHYLENEDIOXYMETHAMPHETAMINE ECSTASY; METHYLENEDIOXYMETHAMPHETAMINE MDMA AB Although a wealth of knowledge exists regarding the acute pharmacological effects of recreational drugs on the CNS, much less is known about the long-term toxic effects of recreational drugs on the CNS. Recent findings in nonhuman primates treated with amphetamine analogs, such as +/- 3,4-methylenedioxymethamphetamine (MDMA), indicate that these drugs can produce long-lasting, probably permanent, changes in brain serotonin innervation. Similarly, animals treated with phencyclidine (PCP) and related drugs develop neurodegenerative changes in selected brain regions. It seems clear, then, that some psychoactive drugs have the potential to produce persistent changes in CNS structure and, possibly, function. The goal of this article is to summarize current knowledge regarding the long-term effects of several popular recreational drugs, including MDMA and related amphetamine analogs, cocaine, marijuana, alcohol, PCP, lysergic acid (LSD), and opiates. Gaps in the current knowledge base are identified, and areas ripe for future research efforts are suggested. C1 NIMH,BIOL PSYCHIAT BRANCH UDM,IRP,BETHESDA,MD 20892. JOHNS HOPKINS MED INST,DEPT NEUROL,BALTIMORE,MD 21205. NR 195 TC 12 Z9 13 U1 3 U2 13 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD NOV PY 1997 VL 3 IS 6 BP 399 EP 411 DI 10.1177/107385849700300613 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA YK579 UT WOS:A1997YK57900013 ER PT J AU Laske, DW Muraszko, KM Oldfield, EH DeVroom, HL Sung, C Dedrick, RL Simon, TR Colandrea, J Copeland, C Katz, D Greenfield, L Groves, ES Houston, LL Youle, RJ AF Laske, DW Muraszko, KM Oldfield, EH DeVroom, HL Sung, C Dedrick, RL Simon, TR Colandrea, J Copeland, C Katz, D Greenfield, L Groves, ES Houston, LL Youle, RJ TI Intraventricular immunotoxin therapy for leptomeningeal neoplasia SO NEUROSURGERY LA English DT Article DE antibody; cancer; cerebrospinal fluid; pharmacokinetics; ricin toxin ID CEREBROSPINAL-FLUID SYSTEM; CENTRAL NERVOUS-SYSTEM; MONOCLONAL-ANTIBODY; TRANSFERRIN RECEPTORS; MENINGEAL CARCINOMATOSIS; BREAST-CANCER; PHASE-I; CHAIN IMMUNOTOXIN; PROTEIN-SYNTHESIS; RHESUS-MONKEYS AB OBJECTIVE: The goals of this clinical trial of intraventricular 454A12-rRA therapy were to identify dose-limiting toxicities, to evaluate the pharmacokinetics of single-dose intraventricular 454A12-rRA, and to detect antitumor activity. METHODS: We performed a pilot study of intraventricular therapy with the immunotoxin 454A12-rRA in eight patients with leptomeningeal spread of systemic neoplasia. The immunotoxin 454A12-rRA is a conjugate of a monoclonal antibody against the human transferrin receptor and recombinant ricin A chain, the enzymatically active subunit of the protein toxin ricin. Patients were treated with single doses of 454A12-rRA ranging from 1.2 to 1200 mu g. RESULTS: The early phase half-life of 454A12-rRA in ventricular cerebrospinal fluid (CSF) averaged 44 +/- 21 minutes, and the late phase half-life averaged 237 +/- 86 minutes. The clearance of the immunotoxin was faster than the clearance of coinjected technetium-99m-diethylenetriamine penta-acetic acid, averaging approximately 2.4-fold greater. No 454A12-rRA degradation was detected by Western blot analysis of ventricular CSF for a period of 24 hours, and bioactivity was retained in CSF paralleling the concentration of immunotoxin. No acute or chronic drug toxicity was identified in patients who received less than or equal to 38 mu g of 454A12-rRA by intraventricular injection. Doses more than or equal to 120 mu g caused a CSF inflammatory response that was associated with transient headache, vomiting, and altered mental status, This acute syndrome was responsive to steroids and CSF drainage. No systemic toxicity was detected. In four of the eight patients, a greater than 50% reduction of tumor cell counts in the lumbar CSF occurred within 5 to 7 days after the intraventricular dose of 454A12-rRA; however, no patient had their CSF cleared of tumor, and clinical or magnetic resonance imaging evidence of tumor progression was demonstrated in seven of the eight patients after treatment. CONCLUSION: Tumoricidal concentrations of the immunotoxin 454A12-rRA can be attained safely in the CSF of patients with leptomeningeal tumor spread. C1 NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. NCI,DEPT NUCL MED,NATL CTR RES RESOURCES,DIV INTRAMURAL RES RESOURCES,BETHESDA,MD 20892. NCI,CTR CLIN,DIV CANC BIOL & DIAGNOSIS,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NINCDS,OFF CLIN DIRECTOR,NIH,BETHESDA,MD 20892. CETUS CORP,EMERYVILLE,CA 94608. NR 72 TC 51 Z9 54 U1 0 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD NOV PY 1997 VL 41 IS 5 BP 1039 EP 1049 DI 10.1097/00006123-199711000-00005 PG 11 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA YE156 UT WOS:A1997YE15600019 PM 9361057 ER PT J AU Batten, D Dyer, KD Domachowske, JB Rosenberg, HF AF Batten, D Dyer, KD Domachowske, JB Rosenberg, HF TI Molecular cloning of four novel murine ribonuclease genes: unusual expansion within the Ribonuclease A gene family SO NUCLEIC ACIDS RESEARCH LA English DT Article ID NONSECRETORY RIBONUCLEASE; EVOLUTION; SEQUENCE; PURIFICATION; EXPRESSION; CDNA AB We have characterized four novel murine ribonuclease genes that,together with the murine eosinophil-associated ribonucleases 1 and 2, form-a distinct and unusual cluster within the RNase A gene superfamily. Three of these genes (mR-3, mR-4, mR-5) include complete open reading frames, encoding ribonucleases with eight cysteines and appropriately spaced histidines (His11 and His124) and lysine (Lys35) that are characteristic of this enlarging protein family; the fourth sequence encodes a non-functional pseudogene (mR-6P), Although the amino acid sequence similarities among these murine ribonucleases varies from 60 to 94%, they form a unique cluster, as each sequence is found to be more closely related to another of this group than to either murine angiogenin or to murine pancreatic ribonuclease, Interestingly, the relationship between the six genes in this 'mR cluster' and the defined lineages of the RNase A gene family could riot be determined by amino acid sequence homology, suggesting the possibility that there are one or more additional ribonuclease lineages that have yet to be-defined, Although the nature of the evolutionary constraints promoting this unusual expansion and diversification remain unclear, the implications with respect to function are intriguing. C1 NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. NR 24 TC 29 Z9 33 U1 0 U2 1 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 NOV 1 PY 1997 VL 25 IS 21 BP 4235 EP 4239 DI 10.1093/nar/25.21.4235 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YG737 UT WOS:A1997YG73700010 PM 9336452 ER PT J AU Andreoli, JM Jang, SI Chung, E Coticchia, CM Steinert, PM Markova, NG AF Andreoli, JM Jang, SI Chung, E Coticchia, CM Steinert, PM Markova, NG TI The expression of a novel, epithelium-specific ets transcription factor is restricted to the most differentiated layers in the epidermis SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA-BINDING DOMAIN; PROXIMAL PROMOTER; JUNB PROMOTER; GENE; PROTEIN; IDENTIFICATION; DROSOPHILA; FAMILY; REGION; CELLS AB Ets proteins have been implicated in the regulation of gene expression during a variety of biological processes, including growth control, differentiation, development and transformation, More than 35 related proteins containing the 'ets domain' have now been found which specifically interact with DNA sequences encompassing the core tetranucleotide GGAA. Although ets responsive genes have been identified in the epidermis, little is known about their distribution and function in this tissue, We have now demonstrated that epidermis and cultured epidermal keratinocytes synthesize numerous ets proteins, The expression of some of these proteins is regulated as a function of differentiation, Among these is a novel ets transcription factor with a dual DNA-binding specificity, which we have called jen. The expression of jen is not only epithelial specific, but it is the only ets protein so far described, and one of the very few transcription factors whose expression is restricted to the most differentiated epidermal layers, We show that two epidermal marker genes whose expression coincides with that of jen are transregulated by this protein in a complex mode which involves interactions with other transcriptional regulators such as Sp1 and AP1. C1 NIAMS,SKIN BIOL LAB,NIH,BETHESDA,MD 20892. NR 53 TC 81 Z9 82 U1 0 U2 0 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 NOV 1 PY 1997 VL 25 IS 21 BP 4287 EP 4295 DI 10.1093/nar/25.21.4287 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YG737 UT WOS:A1997YG73700017 PM 9336459 ER PT J AU Wagner, KU Wall, RJ StOnge, L Gruss, P WynshawBoris, A Garrett, L Li, ML Furth, PA Hennighausen, L AF Wagner, KU Wall, RJ StOnge, L Gruss, P WynshawBoris, A Garrett, L Li, ML Furth, PA Hennighausen, L TI Cre-mediated gene deletion in the mammary gland SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SITE-SPECIFIC RECOMBINATION; TETRACYCLINE-RESPONSIVE PROMOTER; TISSUE PLASMINOGEN-ACTIVATOR; ACIDIC PROTEIN GENE; TRANSGENIC MICE; TEMPORAL CONTROL; HA-RAS; EXPRESSION; MOUSE; CELLS AB To delete genes specifically from mammary tissue using the Cre-lox system,we have established transgenic mice expressing Cre recombinase under control of the WAP gene promoter and the MMTV LTR, Cre activity in these mice was evaluated by three criteria. First, the tissue distribution of Cre mRNA was analyzed, Second, an adenovirus carrying a reporter gene was used to determine expression at the level of single cells. Third, tissue specificity of Cre activity was determined in a mouse strain carrying a reporter gene, In adult MMTV-Cre mice expression of the transgene was confined to striated ductal cells of the salivary gland and mammary epithelial cells in virgin and lactating mice. Expression; of WAP-Cre was only detected in alveolar epithelial cells of mammary tissue during lactation, Analysis of transgenic mice carrying both the MMTV-Cre and the reporter transgenes revealed recombination in every tissue, In contrast, recombination mediated by Cre under control of the WAP gene promoter was largely restricted to the mammary gland but occasionally observed in the brain. These results show that transgenic mice with WAP-Cre but not MMTV-Cre can be used as a powerful tool to study gene function in development and tumorigenesis in the mammary gland. C1 NIDDKD,METAB & BIOCHEM LAB,NIH,BETHESDA,MD 20892. NIH,NATL HUMAN GENOME RES INST,GENET DIS RES LAB,BETHESDA,MD 20892. USDA,BELTSVILLE,MD 20725. UNIV MARYLAND,SCH MED,DEPT MED,DIV INFECT DIS,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,INST HUMAN VIROL,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21201. MAX PLANCK INST BIOPHYS CHEM,DEPT MOL CELL BIOL,ABT 160,D-37018 GOTTINGEN,GERMANY. RI Wagner, Kay-Uwe/B-6044-2009 NR 27 TC 313 Z9 317 U1 0 U2 7 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 NOV 1 PY 1997 VL 25 IS 21 BP 4323 EP 4330 DI 10.1093/nar/25.21.4323 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YG737 UT WOS:A1997YG73700022 PM 9336464 ER PT J AU Schneider, TD AF Schneider, TD TI Sequence walkers: a graphical method to display how binding proteins interact with DNA or RNA sequences SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SITE-SPECIFIC RECOMBINATION; ESCHERICHIA-COLI; MOLECULAR MACHINES; NUCLEOTIDE-SEQUENCE; INFORMATION-CONTENT; CHANNEL CAPACITY; PHAGE LAMBDA; FIS PROTEIN; INTEGRATION; MUTATIONS AB A graphical method is presented for displaying how binding proteins and other macromolecules interact with individual bases of nucleotide sequences. Characters representing the sequence are either oriented normally and placed above a line indicating favorable contact, or upside-down and placed below the line indicating unfavorable contact. The positive or negative height of each letter shows the contribution of that base to the average sequence conservation of the binding site, as represented by a sequence logo. These sequence 'walkers' can be stepped along raw sequence data to visually search for binding sites. Many walkers, for the same or different proteins, can be simultaneously placed next to a sequence to create a quantitative map of a complex genetic region. One can alter the sequence to quantitatively engineer binding sites. Database anomalies can be visualized by placing a walker at the recorded positions of a binding molecule and by comparing this to locations found by scanning the nearby sequences. The sequence can also be altered to predict whether a change is a polymorphism or a mutation for the recognizer being modeled. RP Schneider, TD (reprint author), NCI, FREDERICK CANC RES & DEV CTR, MATH BIOL LAB, POB B, FREDERICK, MD 21702 USA. OI Schneider, Thomas/0000-0002-9841-1531 NR 46 TC 70 Z9 70 U1 2 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 1 PY 1997 VL 25 IS 21 BP 4408 EP 4415 DI 10.1093/nar/25.21.4408 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YG737 UT WOS:A1997YG73700034 PM 9336476 ER PT J AU Chen, M Compton, ST Coviello, VF Green, ED Ashlock, MA AF Chen, M Compton, ST Coviello, VF Green, ED Ashlock, MA TI Transient gene expression from yeast artificial chromosome DNA in mammalian cells is enhanced by adenovirus SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TRANSGENIC MICE; YAC AB The introduction of high molecular weight DNA into mammalian cells is useful for gene expression studies. However, current transfection strategies are inefficient, necessitating propagation of stable DNA transformants prior to analysis of gene expression, Here we demonstrate that transient lipid-mediated DNA transfection can be used to assess gene expression from yeast artificial chromosomes (YACs) containing the 230 kb cystic fibrosis transmembrane conductance regulator gene (CFTR) and Escherichia coli lacZ, We also show that psoralen-UV inactivated adenovirus significantly enhances transfection efficiency. The ability to deliver high molecular weight DNA using lipid-mediated transfection should expedite the analysis of large human genes contained within artificial chromosome vectors. C1 NATL HUMAN GENOME RES INST,GENET & MOL BIOL BRANCH,VECTOR DEV SECT,NIH,BETHESDA,MD 20892. NATL HUMAN GENOME RES INST,GENOME TECHNOL BRANCH,NIH,BETHESDA,MD 20892. NR 17 TC 4 Z9 4 U1 0 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 NOV 1 PY 1997 VL 25 IS 21 BP 4416 EP 4418 DI 10.1093/nar/25.21.4416 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YG737 UT WOS:A1997YG73700035 PM 9336477 ER PT J AU Kirke, PN Mills, JL Scott, JM AF Kirke, PN Mills, JL Scott, JM TI Homocysteine metabolism in pregnancies complicated by neural tube defects SO NUTRITION LA English DT Editorial Material ID GENETIC RISK FACTOR; METHYLENETETRAHYDROFOLATE REDUCTASE; MILD HYPERHOMOCYSTEINEMIA; COMMON MUTATION; SPINA-BIFIDA; DISEASE; PREVENTION; FOLATE C1 Hlth Res Board Ireland, Dublin, Ireland. NICHHD, NIH, Bethesda, MD 20892 USA. RP Kirke, PN (reprint author), Hlth Res Board Ireland, Dublin, Ireland. NR 18 TC 10 Z9 10 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0899-9007 J9 NUTRITION JI Nutrition PD NOV-DEC PY 1997 VL 13 IS 11-12 BP 994 EP 995 DI 10.1016/S0899-9007(97)82079-5 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA YM615 UT WOS:000071082500014 PM 9433721 ER PT J AU Hildesheim, A Han, CL Brinton, LA Kurman, RJ Schiller, JT AF Hildesheim, A Han, CL Brinton, LA Kurman, RJ Schiller, JT TI Human papillomavirus type 16 and risk of preinvasive and invasive vulvar cancer: Results from a seroepidemiological case-control study SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; VIRUS-LIKE PARTICLES; INTRAEPITHELIAL NEOPLASIA; SEROLOGIC RESPONSE; ETIOLOGY; ANTIBODIES; INSITU; DNA AB Objective: To examine whether human papillomavirus (HPV) type 16 is involved in the etiology of vulvar carcinomas. Methods: We studied 142 histologically confirmed cases of vulvar intraepithelial neoplasia (VIN) grade 3 and invasive vulvar cancer and 126 community controls. In addition to a detailed questionnaire through which we obtained information on putative risk factors for vulvar cancer, blood samples were collected from participating subjects and tested for the presence of antibodies to HPV-16 virus-like particles. Data were analyzed by logistic regression. Results: Subjects positive for HPV-16 antibodies were at a 5.3-fold increased risk of vulvar neoplasia (95% confidence interval [CI] 2.5, 11.1), and subjects with high antibody levels were at a 20-fold increased risk of disease (95% CI 5.4, 76.7). A stranger association between HPV-16 seropositivity and disease was observed for VIN grade 3 (odds ratio [OR] 13.4; 95%: CI 3.9, 46.5) than for invasive disease (OR 2.9; 95% CI 0.94, 8.7), and for invasive tumors, there was a suggestion that the association was stronger for women diagnosed with squamous carcinoma of basaloid and/or warty types (OR 3.8; 95% CI 0.76, 18.9) than for those diagnosed with keratinizing squamous cell carcinomas (OR 1.6; 95% CI 0.35, 7.4). Number of sexual partners and herpes simplex virus type 2 seropositivity remained as independent risk factors for vulvar neoplasia after control for confounding by HPV-IC. The risk associated with HPV-16 seropositivity was higher among smokers (CIR 8.5; 95% CI 3.8, 19) than among nonsmokers (OR 3.4; 95% CI 0.85, 13). Conclusion: Our results confirm that HPV is associated with vulvar carcinomas. Findings also suggest the possibility that other sexually transmitted agents might be involved in the etiology of same vulvar tumors and that smoking may be an important cofactor involved in the etiology of HPV-related vulvar tumors. Evaluation of the role of HPV types other than HPV-16 in the etiology of vulvar cancer is needed, and additional efforts aimed at further elucidating the sole of smoking and other cofactors in this disease process are warranted. (C) 1997 by The American College of Obstetricians and Gynecologists. C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV HOSP,DEPT PATHOL,BALTIMORE,MD 21287. RP Hildesheim, A (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EPN,ROOM 443,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 22 TC 54 Z9 59 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 NOV PY 1997 VL 90 IS 5 BP 748 EP 754 DI 10.1016/S0029-7844(97)00467-5 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA YB816 UT WOS:A1997YB81600010 PM 9351758 ER PT J AU Gardner, MO Papile, LA Wright, LL AF Gardner, MO Papile, LA Wright, LL TI Antenatal corticosteroids in pregnancies complicated by preterm premature rupture of membranes SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID NEONATAL RESEARCH NETWORK; BIRTH-WEIGHT INFANTS; STEROIDS AB In 1994, the National Institutes of Health Consensus Development Conference on Antenatal Steroids recommended corticosteroids between 24 and 30-32 weeks' gestation in pregnancies complicated by preterm premature rupture of membranes (FROM). Since the Consensus Conference, the use of antenatal corticosteroids has increased to approximately 60% of potential treatment candidates. Some of the remaining 40% of pregnant candidates may go untreated because of concern that corticosteroids could increase the risk of neonatal infection. Using decision-analysis techniques, we compared the potential benefit of antenatal corticosteroids in reducing the incidence of severe intraventricular hemorrhage with the potential risk of increasing the rate of neonatal sepsis. Our analysis indicates that the benefit of a small decrease in severe intraventricular hemorrhage outweighs the potential harm of a large increase in the rate of neonatal sepsis. Therefore, we support the Consensus Conference panel's recommendation that antenatal corticosteroids be used in pregnancies complicated by preterm FROM. (C) 1997 by The American College of Obstetricians and Gynecologists. C1 UNIV NEW MEXICO, SCH MED, DEPT PEDIAT, ALBUQUERQUE, NM 87131 USA. NATL INST CHILDHOOD HLTH & DEV, NIH, BETHESDA, MD USA. RP Gardner, MO (reprint author), UNIV NEW MEXICO, HLTH SCI CTR, DEPT OBSTET & GYNECOL, SCH MED, 2211 LOMAS BLVD NE, ALBUQUERQUE, NM 87131 USA. NR 13 TC 18 Z9 21 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 NOV PY 1997 VL 90 IS 5 BP 851 EP 853 DI 10.1016/S0029-7844(97)00404-3 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA YB816 UT WOS:A1997YB81600031 PM 9351778 ER PT J AU Yamashita, T Tanaka, Y Ludlow, CL AF Yamashita, T Tanaka, Y Ludlow, CL TI Effects of stimulus intensity on laryngeal long latency responses in awake humans SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID BRAIN-STEM; NERVE-STIMULATION; ANESTHETIZED CAT; AFFERENT-FIBERS; REFLEX; RECEPTORS; NUCLEUS; DOG; CO2; AIR AB Percutaneous electrical stimulation applied to the internal branch of the superior laryngeal nerve (ISLN) results in two long latency laryngeal adductor responses in awake humans: an ipsilateral thyroarytenoid (TA) R1 muscle response at 16 ms, and later bilateral TA R2 muscle responses at 60 ms. The purpose of this study was to determine whether a functional relationship existed between the R1 and R2 responses by gradually increasing the level of electrical stimulation from threshold to supramaximal levels. R1 amplitude increased linearly with stimulation intensity in 9 of the 11 subjects, whereas R2 only had a positive linear relationship in 3 subjects and a negative relationship with stimulation intensity in 1 subject. Significant negative relationships were found between response latency and stimulation intensity in 3 subjects for the R1 responses and 3 other subjects for the R2 responses. Overall, R1 amplitudes increased systematically, whereas R2 responses varied in latency and amplitude with increasing stimulus intensity. Neither the latencies nor the amplitudes of the two responses were related after adjusting for stimulation intensity within subjects by using par tial correlation coefficients. The R1 and R2 responses were functionally unrelated and most likely have different neural components. C1 NIDCD,VOICE & SPEECH SECT,DIV INTRAMURAL RES,BETHESDA,MD 20892. OI Ludlow, Christy/0000-0002-2015-6171 NR 35 TC 12 Z9 13 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD NOV PY 1997 VL 117 IS 5 BP 521 EP 529 DI 10.1016/S0194-5998(97)70025-1 PG 9 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA YF816 UT WOS:A1997YF81600017 PM 9374178 ER PT J AU Zwerski, S Witebsky, FG Conville, PS Gill, VJ Freifeld, AG AF Zwerski, S Witebsky, FG Conville, PS Gill, VJ Freifeld, AG TI Fatal nocardia pulmonary infection in a child with acquired immunodeficiency syndrome and lymphoid interstitial pneumonitis SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE Nocardia; lymphoid interstitial pneumonitis; human immunodeficiency virus infection; opportunistic infection C1 NCI,MICROBIOL SERV,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. RP Zwerski, S (reprint author), NCI,DEPT NURSING,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892, USA. NR 9 TC 3 Z9 3 U1 0 U2 0 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 NOV PY 1997 VL 16 IS 11 BP 1088 EP 1089 DI 10.1097/00006454-199711000-00016 PG 2 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA YF615 UT WOS:A1997YF61500017 PM 9384345 ER PT J AU Grazioso, CF Werner, AL Alling, DW Bishop, PR Buescher, ES AF Grazioso, CF Werner, AL Alling, DW Bishop, PR Buescher, ES TI Antiinflammatory effects of human milk on chemically induced colitis in rats SO PEDIATRIC RESEARCH LA English DT Article ID INTERLEUKIN-1 RECEPTOR ANTAGONIST; ACID-INDUCED COLITIS; HUMAN COLOSTRUM; NECROTIZING ENTEROCOLITIS; POLYMORPHONUCLEAR LEUKOCYTES; BREAST-MILK; INFLAMMATION; PROTECT; DISEASE; MODELS AB We examined the effects of a human milk diet on rats with chemical colitis induced with a 4% acetic acid enema. Colonic myeloperoxidase activity was used as a surrogate marker for neutrophil infiltration. Control rats fed rat chow had little colonic myeloperoxidase activity; geometric mean, 0.27 U/g of tissue. Rats with colitis fed rat chow had significantly increased colonic myeloperoxidase activity (geometric mean, 6.76 U/g, p < 0.01 versus no colitis), as did rats with colitis fed infant formula or Pedialyte (geometric mean, 6.92 and 8.13 U/g, respectively, both p < 0.01 versus no colitis). Animals with colitis fed human milk had significantly lower colonic myeloperoxidase activity (geometric mean, 2.34 U/g) than did animals with colitis fed either chow or infant formula (p < 0.001). Similar effects were seen in rats with colitis fed infant formula supplemented with recombinant human IL-1 receptor antagonist (geometric mean, 1.95 U/g). These data show that orally administered human milk has an antiinflammatory effect on chemically induced colitis in rats, which may be mediated in part by IL-1 receptor antagonist contained in human milk. C1 EASTERN VIRGINIA MED SCH,CTR PEDIAT RES,NORFOLK,VA 23510. EASTERN VIRGINIA MED SCH,DEPT PATHOL,NORFOLK,VA 23510. CHILDRENS HOSP KINGS DAUGHTERS,NORFOLK,VA 23510. NIAID,DIV INTRAMURAL RES,NIH,BETHESDA,MD 20892. FU NICHD NIH HHS [HD-13021-17] NR 34 TC 15 Z9 17 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD NOV PY 1997 VL 42 IS 5 BP 639 EP 643 DI 10.1203/00006450-199711000-00015 PG 5 WC Pediatrics SC Pediatrics GA YC399 UT WOS:A1997YC39900015 PM 9357937 ER PT J AU Pichichero, ME Deloria, MA Rennels, MB Anderson, EL Edwards, KM Decker, MD Englund, JA Steinhoff, MC Deforest, A Meade, BD AF Pichichero, ME Deloria, MA Rennels, MB Anderson, EL Edwards, KM Decker, MD Englund, JA Steinhoff, MC Deforest, A Meade, BD TI A safety and immunogenicity comparison of 12 acellular pertussis vaccines and one whole-cell pertussis vaccine given as a fourth dose in 15- to 20-month-old children SO PEDIATRICS LA English DT Article DE acellular; adverse reactions; antibody; dipththeria-tetanus-pertussis vaccine; pertussis vaccine; whole cell; whooping cough ID CONTROLLED TRIAL AB Objective. To compare the safety and immunogenicity of 12 different acellular pertussis vaccines combined with diphtheria and tetanus toxoids (DTaP) with one licensed diphtheria, tetanus, and whole-cell pertussis vaccine (DTwP) as a fourth-dose booster in children who had previously received DTaP or DTwP primary vaccinations. Methods. Healthy 15- to 20-month-old children were enrolled at six National Institutes of Health Vaccine Treatment and Evaluation Units. All had been randomly assigned to receive three primary doses of DTaP or DTwP at 2, 4, and 6 months of age as part of an earlier National Institutes of Health multicenter trial of DTaP vaccines in the same Vaccine Treatment and Evaluation Units. Parents recorded the occurrence and magnitude of fever; irritability; and injection site redness, swelling, and pain for 3 days after vaccination. Sera obtained before and 1 month after the booster vaccination were analyzed for antibody to pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbriae (FIM), and pertactin (PRN). Diphtheria and tetanus toroid as well as PT neutralizing (Chinese hamster ovary cell) and whole-cell agglutinating antibodies were measured on a subset of sera. Results. A total of 1293 children contributed fourth-dose reaction data. Reactions were less frequent after DTaP than after DTwP. For children vaccinated with a fourth dose of DTaP, which was the same DTaP as received in the primary series, fever and injection site redness, swelling, and pain increased in prevalence compared with the third dose in the primary series. For children receiving DTaP as a fourth dose, injection site redness and swelling occurred more frequently in DTaP-primed than in DTwP-primed children. Variation in the occurrence of reactions among DTaP vaccines was observed. A total of 1160 paired pre- and postvaccination sera were available for analysis. Serum antibody concentrations before boosting were lower than those obtained 1 month after the primary immunization. After the fourth dose, significant increases in antibodies directed against the included antigens were observed for all vaccines; postbooster vaccination antibody titers differed significantly among the DTaP vaccines. For children primed and boosted with the same DTaP, antibody levels were not directly related to the quantity of antigen included for PT, FHA, and FIM; for PRN, there was a closer relationship. Some DTaP vaccines given as fourth-dose boosters elicited antibody to PRN or FIM in some vaccinees, although the DTaP vaccines were not reported to contain these antigens; these responses were observed more frequently in DTwP-primed children. Agglutinin antibody rises were observed in all groups immunized with four doses of a DTaP vaccine containing FHA or PRN, regardless of whether the vaccine included FIM. Diphtheria and tetanus antibody levels exceeded the presumed protective concentration (0.1 IU/mL for diphtheria and 0.01 IU/mL for tetanus) after the fourth dose for all vaccinees. Conclusion. Although differences were observed in reaction rates among the DTaP vaccines given as a fourth dose, the DTaP vaccines were, in general, associated with fewer adverse events than a US-licensed DTwP. For DTaP vaccines, fever; irritability; and injection site pain, redness, and swelling occurred more frequently after the fourth dose than after the third dose of the same vaccine in the primary series. No DTaP was consistently most or least reactogenic or immunogenic. Although serologic correlates of pertussis immunity are not defined, it is clear that most DTaP vaccines can stimulate comparable or higher serum antibody responses than DTwP for those antigens contained in the vaccine. C1 NIAID,BIOMETRY BRANCH,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,CTR VACCINE DEV,BALTIMORE,MD 21201. ST LOUIS UNIV,SCH MED,DEPT MED,ST LOUIS,MO 63104. VANDERBILT UNIV,SCH MED,DEPT PEDIAT,NASHVILLE,TN 37212. VANDERBILT UNIV,SCH MED,DEPT PREVENT MED,NASHVILLE,TN 37212. BAYLOR COLL MED,DEPT MICROBIOL & IMMUNOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. JOHNS HOPKINS UNIV,BALTIMORE,MD. TEMPLE UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19122. ST CHRISTOPHERS HOSP CHILDREN,PHILADELPHIA,PA 19133. US FDA,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20857. RP Pichichero, ME (reprint author), UNIV ROCHESTER,SCH MED,DEPT MICROBIOL & IMMUNOL,601 ELMWOOD AVE,BOX 672,ROCHESTER,NY 14642, USA. FU NIAID NIH HHS [N01-AI05049, N01-AI05151, N01-AI15096] NR 20 TC 107 Z9 109 U1 0 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 1997 VL 100 IS 5 BP 772 EP 788 DI 10.1542/peds.100.5.772 PG 17 WC Pediatrics SC Pediatrics GA YD739 UT WOS:A1997YD73900004 PM 9346976 ER PT J AU Yeh, SY AF Yeh, SY TI Effects of salicylate on 3,4-methylenedioxymethamphetamine (MDMA)-induced neurotoxicity in rats SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE 3,4-methylenedioxymethamphetamine (MDMA); neurotoxicity; salicylate; 3,4-methylenedioxyamphetamine (MDA); hydroxyl radicals; superoxide radicals ID HYDROXYL RADICAL FORMATION; SPRAGUE-DAWLEY RATS; TERT-BUTYL NITRONE; METHYLENEDIOXYMETHYLAMPHETAMINE MDMA; METHYLENEDIOXYMETHAMPHETAMINE MDMA; TRYPTOPHAN-HYDROXYLASE; SEROTONERGIC DEFICITS; PUTATIVE METABOLITES; BODY-TEMPERATURE; TRANSGENIC MICE AB The drug 3,4-methylenedioxymethamphetamine (MDMA) is a serotonergic neurotoxicant that causes hyperthermia and depletion of serotonin (5-HT) and 5-hydroxy-indole-3-acetic acid (5-HIAA) in the central nervous system. Formation of neurotoxic metabolites of MDMA, e.g., 2,4,5-trihydroxy-methamphetamine and 2,4,5-trihydroxyamphetamine, involves hydroxyl and/or superoxide free radicals. The present study was designed to determine whether the hydroxyl free-radical-trapping agent salicylate could provide protection against MDMA neurotoxicity in rats. In the acute studies, sodium salicylate (12.5-400 mg/kg, calculated as free acid) was injected interperitoneally (IF) 1 h before subscutaneous (SC) injections of MDMA (20 mg/kg as base). In the chronic studies, sodium salicylate (3.1-100 mg/kg) was injected TP 1 h before repeated SC injections of MDMA (10 mg/kg as base, twice daily, at 0830 and 1730 h for 4 consecutive days). Repeated MDMA administration depleted contents of 5-HT and 5-HIAA in the frontal cortex, hippocampus and striatum. Coadministration of salicylate plus MDMA did not significantly alter MDMA-induced depletion of 5-HT and 5-HIAA in these tissues. Thus, salicylate, a hydroxyl free-radical-trapping agent, does not protect against MDMA-induced hyperthermia and depletion of 5-HT and 5-HIAA. These observations suggest that MDMA-induced neurotoxicity may occur mainly through the production of superoxide or other radicals rather than hydroxyl free radicals. Salicylate actually potentiated MDMA-induced hyperthermia and lethality, findings that might be of clinical relevance. Published by Elsevier Science Inc. RP Yeh, SY (reprint author), NIDA,MOL NEUROPSYCHIAT SECT,NEUROSCI BRANCH,INTRAMURAL RES PROGRAM,NIH,BALTIMORE,MD 21224, USA. NR 72 TC 19 Z9 20 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD NOV PY 1997 VL 58 IS 3 BP 701 EP 708 DI 10.1016/S0091-3057(97)90010-1 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA XZ344 UT WOS:A1997XZ34400014 PM 9329062 ER PT J AU Boone, CW Bacus, JW Bacus, JV Steele, VE Kelloff, GJ AF Boone, CW Bacus, JW Bacus, JV Steele, VE Kelloff, GJ TI Properties of intraepithelial neoplasia relevant to cancer chemoprevention and to the development of surrogate end points for clinical trials SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID SQUAMOUS-CELL CARCINOMA; MAMMALIAN GENE AMPLIFICATION; IN-SITU; GENOMIC INSTABILITY; TUMOR PROGRESSION; ACTINIC KERATOSIS; BLADDER-CANCER; COLON-CANCER; ALLELIC LOSS; PROLIFERATION AB Cancer chemoprevention is defined as the prevention of cancer by the administration of diet supplements or drugs, A drug discovery effort should therefore focus on finding agents that will avert the process of intraepithelial neoplasia which precedes invasive cancer, Over 30 agents developed by the chemoprevention program at the National Cancer Institue are being tested against intraepithelial neoplasia of many organ sites in more than 80 clinical trials. Two basic mechanisms underlie the onset and development of intraepithelial neoplasia, First is the development of the two precursor lesions of chronic diffuse epithelial hyperplasia and genomic instability, the latter being produced by ''mutator'' mutations in genes responsible for genomic stability, by gene copy amplification or loss from DNA breakage-fusion-anaphase-bridge cycles, by unequal sister chromatid exchange, and by accumulation of double minutes. Second is the development of multicentric intraepithelial neoplastic lesions which independently progress through each of the following processes at a continuously accelerating rate: clonal evolution, hyperproliferation, production of genomic structural variants, and apoptosis, Recommended chemoprevention strategies based on these mechanisms are (i) the development of better technology for early diagnosis, (ii) the development of multiple agents that block intralesional proliferation at steps along the signal pathway of mitotic signal transduction and along the signal pathway of synthesis of daughter cell components, (iii) the development of nontoxic antiinflammatory agents, anitoxidants, antimutagens, and proapoptotics, (iv) the avoidance of ''clonal escape'' through use of drug combinations, and (v) the use of computer-assisted quantitative image analysis to assay modulation of surrogate end points in chemoprevention clinical trials. C1 BACUS LABS IMAGING SYST,ELMHURST,IL 60126. RP Boone, CW (reprint author), NCI,DIV CANC PREVENT & CONTROL,CHEMOPREVENT BRANCH,NIH,BETHESDA,MD 20892, USA. NR 73 TC 34 Z9 34 U1 0 U2 2 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 NOV PY 1997 VL 216 IS 2 BP 151 EP 165 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA YA909 UT WOS:A1997YA90900004 PM 9349684 ER PT J AU Warren, AJ Shields, PG AF Warren, AJ Shields, PG TI Molecular epidemiology: Carcinogen-DNA adducts and genetic susceptibility SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Review ID GLUTATHIONE-S-TRANSFERASE; WHITE BLOOD-CELLS; HYDROCARBON HYDROXYLASE-ACTIVITY; LUNG-CANCER PATIENTS; FRAGMENT-LENGTH-POLYMORPHISM; HUMAN URINARY-BLADDER; HEME-BINDING REGION; COKE-OVEN WORKERS; N-ACETYLTRANSFERASE; CIGARETTE-SMOKING AB Molecular epidemiological studies assess individual chemical exposures and genetic susceptibility in order to identify cancer risk, Such studies incorporate the development, application, and validation of biomarkers of cancer risk in order to enhance cancer risk assessments, focus cancer prevention strategies, and elucidate mechanisms of carcinogenesis, Current studies of molecular epidemiology are based upon an understanding of the complex, multistage process of carcinogenesis and interindividual variations in response to carcinogenic exposures, Quantitative methods to measure human exposures to carcinogens continue to improve and have been successfully applied to a number of epidemiological studies. Genetic predispositions to cancer, both inherited and acquired, have been and continue to be identified, The combined approach of associating genetic polymorphisms with carcinogen-DNA adduct measurements, in order to assess cancer risk, is showing considerable promise, It is hoped that, in the future, molecular epidemiologists will be able to develop a risk profile for an individual that Includes assessment of multiple biomarkers. The field has the near-term potential to have a significant impact on regulatory quantitative risk assessments, which may aid in the determination of allowable exposures, Molecular epidemiological data may also aid in the identification of individuals who will most benefit by cancer prevention strategies. C1 NCI, HUMAN CARCINOGENESIS LAB, DIV BASIC SCI, NIH, BETHESDA, MD 20892 USA. RI Shields, Peter/I-1644-2012 NR 120 TC 15 Z9 16 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD NOV PY 1997 VL 216 IS 2 BP 172 EP 180 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA YA909 UT WOS:A1997YA90900006 PM 9349686 ER PT J AU Tangrea, JA AF Tangrea, JA TI Patient participation and compliance in cancer chemoprevention trials: Issues and concerns SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID RANDOMIZED CLINICAL-TRIALS; PREVENTION TRIALS; ATTITUDES; VIEWPOINTS; KNOWLEDGE; BARRIERS; CONSENT; DRUG AB Cancer chemoprevention trials have unique characteristics that make the tasks of participant recruitment, enrollment, and long-term adherence to the study protocol and intervention regimen especially difficult, Barriers to patient accrual, long-term participation, and optimal adherence are inherent in clinical trial design and organization, and are frequently associated with the attitudes and behavioral dynamics of physicians and the participants themselves. Attracting racially and ethnically diverse populations to trial participation adds additional problems and considerations. Careful planning early in the design phase of a chemoprevention clinical trial must take into account these numerous issues, Clinical investigators should seek expert advice from a number of health care disciplines to better design chemoprevention protocols that minimize logistic complexity, maximize participant eligibility, simplify data collection, and take into account the complex behavioral dynamics of the clinical trial process. RP Tangrea, JA (reprint author), NCI,DIV CANC PREVENT & CONTROL,CANC PREVENT STUDIES BRANCH,NIH,EPN 211,6130 EXECUT BLVD,MSC 7326,BETHESDA,MD 20892, USA. NR 38 TC 15 Z9 15 U1 1 U2 4 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 NOV PY 1997 VL 216 IS 2 BP 260 EP 265 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA YA909 UT WOS:A1997YA90900015 PM 9349695 ER PT J AU Giedd, JN Castellanos, FX Rajapakse, JC Vaituzis, AC Rapoport, JL AF Giedd, JN Castellanos, FX Rajapakse, JC Vaituzis, AC Rapoport, JL TI Sexual dimorphism of the developing human brain SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE adolescent; brain; child; MRI; sex ID DEFICIT-HYPERACTIVITY DISORDER; TOURETTES-SYNDROME; CORPUS-CALLOSUM; BASAL GANGLIA; MRI; CHILDREN; ADOLESCENTS; RELIABILITY; MORPHOLOGY; PATTERNS AB 1. Sexual dimorphism of human brain anatomy has not been well-studied between 4 and 18 years of age, a time of emerging sex differences in behavior and the sexually specific hormonal changes of adrenarche (the predominantly androgenic augmentation of adrenal cortex function occurring at approximately age 8) and puberty. 2. To assess sex differences in brain structures during this developmental period volumes of the cerebrum, lateral ventricles, caudate, putamen, globus pallidus temporal lobe, amygdala, and hippocampus, and midsagittal area measurements of the corpus callosum were quantified from brain magnetic resonance images of 121 healthy children and adolescent and examined in relation to age and sex. 3. Males had a 9% larger cerebral volume. When adjusted for cerebral volume by ANCOVA only the basal ganglia demonstrated sex differences in mean volume with the caudate being relatively larger in females and the globus pallidus being relatively larger in males. The lateral Ventricles demonstrated a prominent sex difference in brain maturation with robust increases in size in males only. A piecewise-linear model revealed a significant change in the linear regression slope of lateral ventricular volume in males after age 11 that was not shared by females at that or other ages. 4. Amygdala and hippocampal volume increased for both sexes but with the amygdala increasing significantly more in males than females and hippocampal volume increasing more in females. 5. These sexually dimorphic patterns of brain development may be related to the observed sex differences in age of onset, prevalence, and symptomatology seen in nearly all neuropsychiatric disorders of childhood. RP Giedd, JN (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,10 CTR DR,MSC 1600,BETHESDA,MD 20892, USA. RI Giedd, Jay/A-3080-2008; Rajapakse, Jagath/B-8485-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Rajapakse, Jagath/0000-0001-7944-1658; Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 55 TC 279 Z9 282 U1 5 U2 25 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD NOV PY 1997 VL 21 IS 8 BP 1185 EP 1201 DI 10.1016/S0278-5846(97)00158-9 PG 17 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA YK528 UT WOS:A1997YK52800002 PM 9460086 ER PT J AU Hejtmancik, JF Wingfield, PT Chambers, C Russell, P Chen, HC Sergeev, YV Hope, JN AF Hejtmancik, JF Wingfield, PT Chambers, C Russell, P Chen, HC Sergeev, YV Hope, JN TI Association properties of beta B2- and beta A3-crystallin: ability to form dimers SO PROTEIN ENGINEERING LA English DT Article DE crystallin; lens; association; recombinant; mouse ID EYE LENS; TERMINAL EXTENSION; CIRCULAR-DICHROISM; CRYSTALLIN GENE; CALF; AGGREGATION; SEQUENCE; PROTEINS; BETA-B2-CRYSTALLIN; RESOLUTION AB The beta-crystallins are a major constituent of the mammalian lens, where they associate into dimers, tetramers and higher order aggregates, Appropriate association of lens crystallins is important for lens transparency, To examine the associative properties of beta B2-crystallin, we have expressed mouse beta B2-crystallin using a baculovirus system, Recombinant mouse beta B2-crystallin has an estimated monomer molecular weight of 24 kDa by SDS-PAGE, appropriate immunoreactivity and appropriate secondary structure as assessed by circular dichroism analysis, The recombinant beta B2-crystallin associates into a homodimer with a weight average molecular mass of 39 kDa, The beta B2-crystallin homodimer has an estimated K(d) of 5 x 10(-6) M, slightly greater than that of beta A3-crystallin, 0.8 x 10(-6) M. When recombinant beta B2-crystallin is combined with recombinant beta A3-crystallin, a heterodimer is formed within 10 min of incubation at room temperature, When equilibrium is reached in 4-6 h, approximately half of each crystallin associates into heterodimers. Subunit exchange between beta B2-crystallin and beta A3-crystallin occurs readily in the absence of any denaturing agents, Thus, r beta A3-r beta B2 heterodimer formation can occur under conditions similar to those found in the eye lens. C1 NEI, Ophthalmol Genet & Clin Serv Branch, Lab Mechanisms Ocular Dis, NIH, Bethesda, MD 20892 USA. NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. RP Hejtmancik, JF (reprint author), NEI, Ophthalmol Genet & Clin Serv Branch, Lab Mechanisms Ocular Dis, NIH, Bethesda, MD 20892 USA. NR 34 TC 44 Z9 44 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD NOV PY 1997 VL 10 IS 11 BP 1347 EP 1352 DI 10.1093/protein/10.11.1347 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA YY097 UT WOS:000072112300014 PM 9514125 ER PT J AU Hebert, EJ Grimsley, GR Hartley, RW Horn, G Schell, D Garcia, S Both, V Sevcik, J Pace, CN AF Hebert, EJ Grimsley, GR Hartley, RW Horn, G Schell, D Garcia, S Both, V Sevcik, J Pace, CN TI Purification of ribonucleases Sa, Sa2, and Sa3 after expression in Escherichia coli SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID STREPTOMYCES-AUREOFACIENS; CONFORMATIONAL STABILITY; RESOLUTION; COMPLEX; SPECIFICITY; PROTEINS; BARSTAR; CLONING; GENE AB The genes for three small ribonucleases from different strains of Streptomyces aureofaciens have been cloned and expressed in Escherichia coli. The purification of these ribonucleases from the periplasmic space is described, The yields range from 10 to 50 mg of protein per liter of culture medium. The molar absorption coefficients, isoelectric pH values, and pH of optimum activity are reported. (C) 1997 Academic Press. C1 TEXAS A&M UNIV,DEPT MED BIOCHEM & GENET,COLLEGE STN,TX 77843. TEXAS A&M UNIV,CTR MACROMOL DESIGN,COLLEGE STN,TX 77843. NIDDKD,CELLULAR & DEV BIOL LAB,NIH,BETHESDA,MD 20892. SLOVAK ACAD SCI,INST MOL BIOL,BRATISLAVA 84251,SLOVAKIA. RP Hebert, EJ (reprint author), TEXAS A&M UNIV,DEPT BIOCHEM & BIOPHYS,COLLEGE STN,TX 77843, USA. FU NIGMS NIH HHS [GM 37039] NR 35 TC 48 Z9 48 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 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD NOV PY 1997 VL 11 IS 2 BP 162 EP 168 DI 10.1006/prep.1997.0776 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA YE722 UT WOS:A1997YE72200002 PM 9367812 ER PT J AU Huth, JR Bewley, CA Jackson, BM Hinnebusch, AG Clore, GM Gronenborn, AM AF Huth, JR Bewley, CA Jackson, BM Hinnebusch, AG Clore, GM Gronenborn, AM TI Design of an expression system for detecting folded protein domains and mapping macromolecular interactions by NMR SO PROTEIN SCIENCE LA English DT Article DE domain structure; GBI-fusion protein; intermolecular interactions; NMR ID ESCHERICHIA-COLI; BINDING DOMAIN; SPECTROSCOPY; PURIFICATION; FUSION; BETA; VECTORS; GENE AB Two protein expression vectors have been designed for the preparation of NMR samples. The vectors encode the immunoglobulin-binding domain of streptococcal protein G (GB1 domain) linked to the N-terminus of the desired proteins. This fusion strategy takes advantage of the small size, stable fold, and high bacterial expression capability of the GB1 domain to allow direct NMR spectroscopic analysis of the fusion protein by H-1-N-15 correlation spectroscopy. Using this system accelerates the initial assessment of protein NMR projects such that, in a matter of days, the solubility and stability of a protein can be determined. In addition, N-15-labeling of peptides and their testing for DNA binding are facilitated. Several examples are presented that demonstrate the usefulness of this technique for screening protein/DNA complexes, as well as for probing ligand-receptor interactions, using N-15-labeled GB1-peptide fusions and unlabeled target. C1 NIDDKD,PHYS CHEM LAB,NIH,BETHESDA,MD 20892. NICHHD,LAB EUKARYOT GENE REGULAT,NIH,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 24 TC 113 Z9 117 U1 0 U2 10 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 NOV PY 1997 VL 6 IS 11 BP 2359 EP 2364 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF614 UT WOS:A1997YF61400009 PM 9385638 ER PT J AU Raghunathan, G Jernigan, RL AF Raghunathan, G Jernigan, RL TI Ideal architecture of residue packing and its observation in protein structures (vol 6, pg 2078, 1997) SO PROTEIN SCIENCE LA English DT Correction, Addition RP Raghunathan, G (reprint author), NCI,MOL STRUCT SECT,LAB EXPT & COMPUTAT BIOL,DIV BASIC SCI,NIH,MSC 5677,12 SOUTH DR,BETHESDA,MD 20892, USA. RI Jernigan, Robert/A-5421-2012 NR 1 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD NOV PY 1997 VL 6 IS 11 BP 2485 EP 2485 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF614 UT WOS:A1997YF61400027 ER PT J AU Wehrle, JP AF Wehrle, JP TI Report on the 1997 Johns Hopkins Protein Folding meeting SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Editorial Material RP Wehrle, JP (reprint author), NIGMS,NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 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 0887-3585 J9 PROTEINS JI Proteins PD NOV PY 1997 VL 29 IS 3 BP 259 EP 263 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YE223 UT WOS:A1997YE22300001 PM 9365982 ER PT J AU Bahar, I Kaplan, M Jernigan, RL AF Bahar, I Kaplan, M Jernigan, RL TI Short-range conformational energies, secondary structure propensities, and recognition of correct sequence-structure matches SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE knowledge-based potentials; virtual bonds; coupling between bond torsions and bond angles; secondary structure propensities; inverse folding experiments ID HELIX-FORMING TENDENCIES; ALPHA-HELIX; AMINO-ACIDS; THERMODYNAMIC SCALE; GLOBULAR PROTEINS; PACKING DENSITY; POTENTIALS; STABILITY; REPRESENTATION; PREDICTION AB A statistical analysis of known structures is made for an assessment of the utility of short-range energy considerations. For each type of amino acid, the potentials governing (1) the torsions and bond angle changes of virtual C-alpha-C-alpha bonds and (2) the coupling between torsion and bond angle changes are derived. These contribute approximately -2 RT per residue to the stability of native proteins, approximately half of which is due to coupling effects. The torsional potentials for the alpha-helical states of different residues are verified to be strongly correlated with the free-energy change measurements made upon single-site mutations at solvent-exposed regions, Likewise, a satisfactory correlation is shown between the beta-sheet potentials of different amino acids and the scales from free-energy measurements, despite the role of tertiary context in stabilizing beta-sheets. Furthermore, there is excellent agreement between our residue-specific potentials for alpha-helical state and other thermodynamic based scales. Threading experiments performed by using an inverse folding protocol show that 50 of 62 test structures correctly recognize their native sequence on the basis of short-range potentials. The performance is improved to 55, upon simultaneous consideration of short-range potentials and the nonbonded interaction potentials between sequentially distant residues, Interactions between near residues along the primary structure, i.e., the local or short-range interactions, are known to be insufficient, alone, for understanding the tertiary structural preferences of proteins alone. Yet, knowledge of short-range conformational potentials permits rationalizing the secondary structure propensities and aids in the discrimination between correct and incorrect tertiary folds. (C) 1997 Wiley-Liss, Inc. C1 NCI,MOL STRUCT SECT,MATH BIOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. BOGAZICI UNIV,CTR POLYMER RES,TR-80815 BEBEK,ISTANBUL,TURKEY. BOGAZICI UNIV,DEPT CHEM ENGN,TR-80815 BEBEK,ISTANBUL,TURKEY. TUBITAK,ADV POLYMER MAT RES CTR,TR-80815 BEBEK,ISTANBUL,TURKEY. RI Jernigan, Robert/A-5421-2012 NR 46 TC 91 Z9 93 U1 2 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-3585 J9 PROTEINS JI Proteins PD NOV PY 1997 VL 29 IS 3 BP 292 EP 308 DI 10.1002/(SICI)1097-0134(199711)29:3<292::AID-PROT4>3.0.CO;2-D PG 17 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YE223 UT WOS:A1997YE22300004 PM 9365985 ER PT J AU Shoaib, M Schindler, CW Goldberg, SR Pauly, JR AF Shoaib, M Schindler, CW Goldberg, SR Pauly, JR TI Behavioural and biochemical adaptations to nicotine in rats: influence of MK801, an NMDA receptor antagonist SO PSYCHOPHARMACOLOGY LA English DT Article DE nicotine; rats; MK801; NMDA receptor ID ANTICONVULSANT MK-801; AUTORADIOGRAPHIC ANALYSIS; CHOLINERGIC RECEPTORS; TOLERANCE; BRAIN; BINDING; SENSITIZATION; CHANNELS; INHIBITION; INFUSION AB Chronic exposure of rats to nicotine can result in sensitization to the stimulant effects of nicotine on locomotor activity. At a biochemical level, chronic exposure to nicotine increases the number of CNS nicotinic binding sites, and this has been suggested as the basis for sensitization to nicotine. The present experiment was conducted to examine the effects of MK801, an NMDA receptor antagonist, on sensitization to nicotine. In addition, the hypothesis that MK801 may block behavioural sensitization by preventing the up-regulation of nicotinic receptors was tested by measuring receptor numbers in the same individuals using quantitative autoradiography with [H-3]-cytisine and [H-3]-MK801. Male Sprague-Dawley rats were chronically treated with nicotine (0.4 mg/kg SC) or saline daily for 7 days. Over the next 2 days, in a counterbalanced order, rats were challenged with nicotine (0.4 mg/kg SC) or saline and locomotor activity was monitored. In saline-pretreated rats, nicotine produced a small increase in activity. Nicotine-pretreated rats exhibited higher levels of activity following a nicotine challenge. This sensitized response was attenuated in rats administered MK801 (0.3 mg/kg IP) 30 min before each daily nicotine injection. Rats pretreated with MK801 alone showed activity scores no different from saline pretreated control groups. Biochemical studies revealed increased [H-3]-cytisine binding following chronic nicotine treatment; however receptor increases were significantly attenuated by MK801 pretreatment. Binding of [H-3]-MK801 remained unchanged across the four groups, The results suggest that MK801 prevents behavioural sensitization to nicotine via the prevention of receptor up-regulation. Although the findings support the notion that receptor up-regulation may be the basis for the increased responsiveness to nicotine, other interpretations are possible. C1 NIDA,PRECLIN PHARMACOL BRANCH,ADDICT RES CTR,BALTIMORE,MD 21224. UNIV KENTUCKY,COLL PHARM,DIV PHARMACOL & EXPT THERAPEUT,LEXINGTON,KY 40536. NR 30 TC 54 Z9 56 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 NOV PY 1997 VL 134 IS 2 BP 121 EP 130 DI 10.1007/s002130050433 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA YG639 UT WOS:A1997YG63900003 PM 9399375 ER PT J AU Terry, P Katz, JL AF Terry, P Katz, JL TI Dopaminergic mediation of the discriminative stimulus effects of bupropion in rats SO PSYCHOPHARMACOLOGY LA English DT Article DE bupropion; cocaine; dopamine transporter; uptake inhibition; antidepressants; drug abuse; drug discrimination; D-1 receptors; D-2 receptors ID SCHEDULE-CONTROLLED BEHAVIOR; PHARMACOLOGICAL CHARACTERIZATION; UPTAKE INHIBITOR; UPTAKE COMPLEX; COCAINE DEPENDENCE; RECEPTOR SUBTYPES; NONHUMAN-PRIMATES; SQUIRREL-MONKEYS; ANTI-DEPRESSANT; HYDROCHLORIDE AB Bupropion is a novel, non-tricyclic antidepressant with a primary pharmacological action of monoamine uptake inhibition. The drug resembles a psychostimulant in terms of its neurochemical and behavioural profiles in vivo, but it does not reliably produce stimulant-like effects in humans at clinically prescribed doses. Bupropion binds with modest selectivity to the dopamine transporter, but its behavioural effects have often been attributed to its inhibition of norepinephrine uptake. This experiment examines monoaminergic involvement in the discriminative stimulus effects of bupropion. Rats were trained to press one lever when injected IP with bupropion (17.0 mg/kg), and another lever when injected with saline. In substitution tests, dose-response curves were obtained for several monoamine uptake inhibitors. Nine of ten dopamine uptake blockers fully substituted fbr bupropion; the exception, indatraline (LU 19-005), partially substituted (71% bupropion-appropriate responding). Serotonin and norepinephrine uptake blockers (zimelidine and nisoxetine, respectively) produced negligible or limited substitution, and the anti-muscarinic dopamine uptake blocker benztropine produced limited partial substitution. A series of dopamine D-1-like and D-2-like receptor agonists were also tested: only the D-2-like agonist RU 24213 fully substituted; three other D-2-like agonists and four D-1-like agonists partially substituted (50% < drug responding < 80%). Antagonism of the discriminative effects of bupropion was obtained with a D-1- and a D-2-like dopamine antagonist. The results demonstrate strong similarities with those obtained using other dopamine uptake inhibitors as training drugs, and support the view that the behavioural effects of bupropion are primarily mediated by dopaminergic mechanisms. C1 NIDA,PSYCHOBIOL SECT,INTRAMURAL RES PROGRAM,NIH,BALTIMORE,MD 21224. OI Katz, Jonathan/0000-0002-1068-1159 NR 79 TC 35 Z9 36 U1 2 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 1997 VL 134 IS 2 BP 201 EP 212 DI 10.1007/s002130050443 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA YG639 UT WOS:A1997YG63900013 PM 9399385 ER PT J AU Berntson, GG Bigger, JT Eckberg, DL Grossman, P Kaufmann, PG Malik, M Nagaraja, HN Porges, SW Saul, JP Stone, PH VanderMolen, MW AF Berntson, GG Bigger, JT Eckberg, DL Grossman, P Kaufmann, PG Malik, M Nagaraja, HN Porges, SW Saul, JP Stone, PH VanderMolen, MW TI Heart rate variability: Origins, methods, and interpretive caveats SO PSYCHOPHYSIOLOGY LA English DT Review DE autonomic nervous system; cardiac chronotropic control; electrocardiogram; heart rate; methodology; parasympathetic; respiratory sinus arrhythmia; sympathetic; vagal tone ID RESPIRATORY SINUS ARRHYTHMIA; ACUTE MYOCARDIAL-INFARCTION; PARASYMPATHETIC CARDIAC CONTROL; BLOOD-PRESSURE VARIABILITY; SYMPATHETIC-NERVE ACTIVITY; POWER SPECTRUM ANALYSIS; CAROTID BARORECEPTOR STIMULI; MIDDLE-AGED PERSONS; R-R INTERVAL; PERIOD VARIABILITY AB Components of heart rate variability have attracted considerable attention in psychology and medicine and have become important dependent measures in psychophysiology and behavioral medicine. Quantification and interpretation of heart rate variability, however, remain complex issues and are fraught with pitfalls. The present report (a) examines the physiological origins and mechanisms of heart rate variability, (b) considers quantitative approaches to measurement, and (c) highlights important caveats in the interpretation of heart rate variability. Summary guidelines for research in this area are outlined, and suggestions and prospects for future developments are considered. C1 COLUMBIA UNIV,NEW YORK,NY. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,RICHMOND,VA 23298. LOWN CARDIOVASC CTR,BROOKLINE,MA. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV LONDON ST GEORGES HOSP,SCH MED,DEPT CARDIOL SCI,LONDON SW17 0RE,ENGLAND. OHIO STATE UNIV,DEPT STAT,COLUMBUS,OH 43210. UNIV MARYLAND,INST CHILD STUDY,COLLEGE PK,MD 20742. CHILDRENS HOSP,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. UNIV AMSTERDAM,DEPT PSYCHOL,AMSTERDAM,NETHERLANDS. RP Berntson, GG (reprint author), OHIO STATE UNIV,DEPT PSYCHOL,1885 NEIL AVE,COLUMBUS,OH 43210, USA. RI Grossman, Paul/A-6279-2009 NR 269 TC 1418 Z9 1444 U1 35 U2 227 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD NOV PY 1997 VL 34 IS 6 BP 623 EP 648 DI 10.1111/j.1469-8986.1997.tb02140.x PG 26 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA YH887 UT WOS:A1997YH88700001 PM 9401419 ER PT J AU White, L AF White, L TI Alzheimer's disease: The evolution of a diagnosis SO PUBLIC HEALTH REPORTS LA English DT Editorial Material C1 NIA,ASIA PACIFIC OFF EPIDEMIOL,DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. NR 2 TC 0 Z9 0 U1 0 U2 1 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD NOV-DEC PY 1997 VL 112 IS 6 BP 495 EP 496 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YK134 UT WOS:A1997YK13400020 PM 10822477 ER PT J AU Hill, SC Baker, AR Barton, NW Wexler, LH Scott, LJC AF Hill, SC Baker, AR Barton, NW Wexler, LH Scott, LJC TI Sciatic nerve: Paradoxic hypertrophy after amputation in young patients SO RADIOLOGY LA English DT Article DE bone neoplasms, in infants and children; bone neoplasms, MR; bones, MR; sarcoma ID PERIPHERAL-NERVES; GROWTH; EXPRESSION; ATROPHY; TUMORS AB PURPOSE: To evaluate the appearance of the sciatic nerve after leg amputation. MATERIALS AND METHODS: Magnetic resonance (MR) images were obtained in seven patients (age at amputation, 11-19 years) who underwent above-knee amputation to treat osteogenic sarcoma. Images were evaluated for sciatic nerve enlargement. Findings were correlated with the time after amputation. RESULTS: All seven patients were found to have a markedly enlarged sciatic nerve in the stump of the amputated leg. The enlargement extended proximally from the point of nerve transection to a level posterior to the femoral neck (8-27 cm) depending on the length of the stump. No evidence of sciatic nerve enlargement was found in the opposite leg or on preoperative MR images that were available in three of the patients. Moreover, in one patient with a sarcoma who underwent a leg-sparing procedure, no sciatic nerve enlargement was seen postoperatively. The thickness of the distal sciatic nerve was related to the time after amputation. CONCLUSION: Hypertrophy of the sciatic nerve occurred after above-knee amputation in young patients. This finding differed from atrophy of the nerve that has been reported previously in older patients. C1 VIRGINIA MED ASSOCIATES,SPRINGFIELD,VA. NINCDS,DEV & METAB BRANCH,NIH,BETHESDA,MD 20892. COLUMBIA PRESBYTERIAN MED CTR,DIV PEDIAT ONCOL,NEW YORK,NY 10032. UNIV VERMONT,DEPT NEUROL,BURLINGTON,VT. RP Hill, SC (reprint author), NIH,DEPT DIAGNOST RADIOL,WARREN GRANT MAGNUSON CLIN CTR,BLDG 10,RM 1C-660,10 CTR DR,BETHESDA,MD 20892, USA. NR 21 TC 5 Z9 5 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 1997 VL 205 IS 2 BP 559 EP 562 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA YD151 UT WOS:A1997YD15100043 PM 9356645 ER PT J AU Langford, CA Sneller, MC Hoffman, GS AF Langford, CA Sneller, MC Hoffman, GS TI Methotrexate use in systemic vasculitis SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID GIANT-CELL ARTERITIS; TRIMETHOPRIM-SULFAMETHOXAZOLE; WEGENERS GRANULOMATOSIS; POLYMYALGIA-RHEUMATICA; TAKAYASU-ARTERITIS; THERAPY; ARTHRITIS; RESISTANT; PANCYTOPENIA; EXPERIENCE AB Recent investigations suggest a beneficial role for methotrexate (MTX) in the treatment of systemic vasculitis. Although glucocorticosteroids (GS) and cyclophosphamide have been the cornerstone of vasculitis therapy, medication toxicity and the potential for relapsing and treatment-resistant disease have prompted the search for other therapeutic options. Weekly low-dose MTX has been found to be an acceptable cytotoxic alternative in patients with Wegener's granulomatosis who do not have immediate life-threatening disease. In Takayasu's arteritis, MTX was observed to be effective in decreasing GS therapy and toxicity in some patients. Giant cell arteritis is another vasculitic disorder for which MTX may have potential value in the treatment of disease and reduction of GS-related complications. C1 CLEVELAND CLIN FDN,DEPT RHEUMAT & IMMUNOL DIS,CLEVELAND,OH 44195. RP Langford, CA (reprint author), NIAID,IMMUNOL DIS SECT,LAB IMMUNOREGULAT,NIH,BLDG 10,ROOM 11B-13,BETHESDA,MD 20892, USA. NR 50 TC 43 Z9 44 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD NOV PY 1997 VL 23 IS 4 BP 841 EP & DI 10.1016/S0889-857X(05)70363-X PG 14 WC Rheumatology SC Rheumatology GA YD927 UT WOS:A1997YD92700008 PM 9361158 ER PT J AU Aneman, A Pettersson, A Eisenhofer, G Friberg, P Holm, M vonBothmer, C Fandriks, L AF Aneman, A Pettersson, A Eisenhofer, G Friberg, P Holm, M vonBothmer, C Fandriks, L TI Sympathetic and renin-angiotensin activation during graded hypovolemia in pigs: Impact on mesenteric perfusion and duodenal mucosal function SO SHOCK LA English DT Article ID ALKALINE SECRETION; FLUID ABSORPTION; RAT; HEMORRHAGE; VASOCONSTRICTION; CIRCULATION; INTESTINE; HUMANS; SYSTEM; CAT AB Sympathetic and angiotensinergic activation reduce splanchnic oxygen delivery during hypovolemia, which may lead to failure of the intestinal mucosal barrier and eventually multiple organ dysfunction. This study integrates sympathetic and angiotensinergic responses with splanchnic hemodynamics and duodenal mucosal function during hypovolemia and evaluates pharmacologic blockade of either system to ameliorate the impact of acute hypovolemia. Chloralose-anesthetized pigs subjected to 20 and 40% blood volume reductions were randomized to controls or administered guanethidine or enalaprilate to block sympathetic and angiotensinergic activation, as assessed by plasma norepinephrine spillover and angiotensin II levels, respectively. Mesenteric and hepatic oxygen delivery/consumption as well as duodenal mucosal alkaline secretion and potential difference were determined. Hypovolemia preferentially increased mesenteric sympathetic outflow and caused a vigorous angiotensinergic activation. Guanethidine and enalaprilate blocked effectively the sympathetic and angiotensinergic responses. Treatment with enalaprilate, but not guanethidine, prevented the reduction of mesenteric oxygenation and duodenal mucosal alkaline secretion and potential difference observed in control animals. The down-regulation of mesenteric oxygenation and duodenal mucosal function during hypovolemia can be prevented by administration of enalaprilate, whereas guanethidine is uneffective in this respect. Interference with the renin-angiotensin system might be of clinical interest to support mesenteric perfusion and organ function in hypovolemia. C1 SAHLGRENS UNIV HOSP,DEPT CLIN PHARMACOL,S-41345 GOTHENBURG,SWEDEN. GOTHENBURG UNIV,DEPT PHYSIOL,S-41390 GOTHENBURG,SWEDEN. GOTHENBURG UNIV,CTR GASTROENTEROL RES,S-41390 GOTHENBURG,SWEDEN. NINCDS,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. RP Aneman, A (reprint author), SAHLGRENS UNIV HOSP,DEPT ANESTHESIOL & CRIT CARE,S-41345 GOTHENBURG,SWEDEN. NR 29 TC 32 Z9 32 U1 0 U2 0 PU BIOMEDICAL PRESS PI AUGUSTA PA 1021 15TH ST, BIOTECH PARK STE 9, AUGUSTA, GA 30901 SN 1073-2322 J9 SHOCK JI Shock PD NOV PY 1997 VL 8 IS 5 BP 378 EP 384 PG 7 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA YD376 UT WOS:A1997YD37600011 PM 9361350 ER PT J AU Mechanic, D AF Mechanic, D TI Managed mental health care SO SOCIETY LA English DT Article RP Mechanic, D (reprint author), RUTGERS STATE UNIV,NIMH,CTR RES ORG & FINANCING CARE SERIOUSLY MENTALLY I,PISCATAWAY,NJ 08855, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU TRANSACTION PERIOD CONSORTIUM PI NEW BRUNSWICK PA DEPT 3091 RUTGERS-THE STATE UNIV OF NJ, NEW BRUNSWICK, NJ 08903 SN 0147-2011 J9 SOCIETY JI Society PD NOV-DEC PY 1997 VL 35 IS 1 BP 44 EP 52 DI 10.1007/s12115-997-1055-9 PG 9 WC Social Sciences, Interdisciplinary; Sociology SC Social Sciences - Other Topics; Sociology GA YA853 UT WOS:A1997YA85300018 ER PT J AU Riker, A Libutti, SK Bartlett, DL AF Riker, A Libutti, SK Bartlett, DL TI Advances in the early detection, diagnosis, and staging of pancreatic cancer SO SURGICAL ONCOLOGY-OXFORD LA English DT Review DE pancreatic cancer; magnetic resonance imaging (MRI); positron emission tomography (PET); laparoscopy; endoscopic ultrasound (EUS); review ID TUMOR-ASSOCIATED ANTIGEN; FINE-NEEDLE ASPIRATION; BILE-DUCT STRICTURES; KI-RAS GENE; SPIRAL CT; CA 19-9; ENDOSCOPIC ULTRASONOGRAPHY; GADOLINIUM ENHANCEMENT; DIFFERENTIAL-DIAGNOSIS; CLINICAL UTILITY AB Pancreatic cancer is an aggressive disease with a dismal prognosis, It has long been regarded as one of the most difficult cancers to accurately diagnose and stage preoperatively, The purpose of this review is to provide an update of the state-of-the-art for early detection, diagnosis, and staging of pancreatic cancer, These methods include spiral CT scans, magnetic resonance imaging, positron emission tomography (PET) imaging, laparoscopy, endoscopic ultrasound, CA 19-9 serology, fine needle aspiration cytology, ERCP brush cytology, and screening for p53 and ras oncogenes, These advanced techniques should help us to detect pancreatic cancers in high-risk populations at a curative stage and to decrease pancreatico-duodenectomies for benign disease which could otherwise be treated with less morbid procedures, In addition, these tests will help reliably diagnose pancreatic cancer preoperatively, (C) 1998 Elsevier Science Ltd. C1 NCI, NIH, Surg Branch, Bethesda, MD 20892 USA. RP NCI, NIH, Surg Branch, Bldg 10,Room 2B16,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 78 TC 36 Z9 37 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0960-7404 EI 1879-3320 J9 SURG ONCOL JI Surg. Oncol.-Oxf. PD NOV PY 1997 VL 6 IS 3 BP 157 EP 169 DI 10.1016/S0960-7404(97)00025-X PG 13 WC Oncology; Surgery SC Oncology; Surgery GA ZE241 UT WOS:000072772300003 PM 9576631 ER PT J AU Noga, JT Hyde, TM Herman, MM Spurney, CF Bigelow, LB Weinberger, DR Kleinman, JE AF Noga, JT Hyde, TM Herman, MM Spurney, CF Bigelow, LB Weinberger, DR Kleinman, JE TI Glutamate receptors in the postmortem striatum of schizophrenic, suicide, and control brains SO SYNAPSE LA English DT Article DE D-aspartate; NMDA; AMPA; kainic acid; glutamate; schizophrenia ID BINDING-SITES; RHESUS-MONKEY; PREFRONTAL CORTEX; QUANTITATIVE AUTORADIOGRAPHY; CORTICAL INPUTS; CAUDATE-NUCLEUS; BASAL GANGLIA; DOPAMINE; RAT; PROJECTIONS AB Introduction: Previous postmortem studies of glutamate receptors and uptake sites have shown decreased D-aspartate (D-Asp) (a marker for the high affinity glutamate uptake site) and elevated (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine maleate (MK-801) binding in the putamen in schizophrenia and elevated alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor binding in the caudate nucleus of schizophrenics who committed suicide. The relative effects of schizophrenia, suicide, and neuroleptic treatment in these findings is unclear. This study further explores binding to glutamate receptors (NMDA, kainic acid, and AMPA) and uptake sites in postmortem striatal structures in schizophrenics relative to three control groups (normal controls, neuroleptic-treated controls, and nonpsychotic suicides). Methods: We compared the binding densities of tritium-labeled ligands 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), kainic acid (KA), MK-801, and D-Asp, which target the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), KA, and N-methyl-D-aspartic acid (NMDA) ionotropic receptor sites and the glutamate uptake site, respectively, in postmortem striatal/accumbens tissue from six DSM-III-R schizophrenics, eight normal controls, eight neuroleptic-treated controls, and eight suicide victims using standard receptor autoradiographic methods. Results: Binding of [H-3] CNQX (AMPA receptors) was significantly different among the four groups across the subdivisions of the striatum: caudate, putamen, and nucleus accumbens (ANOVA P = .0007, .002, and .004, respectively). The schizophrenia group had higher mean CNQX binding in the caudate nucleus than normal (P = .005) and neuroleptic controls (P = .006) but not suicides (P = .6), who were also higher than normals and neuroleptic-treated controls (P = .05). The binding densities of tritiated MK-801, KA, and D-Asp were not significantly different among the four groups of subjects in any of the striatal regions examined. Conclusions: The data suggest there may be an increased density of AMPA receptor sites in the caudate nucleus in schizophrenia that is not apparently due to neuroleptic treatment. A similar increase was also seen the suicide group. Although these data do not confirm previous reports of an increase in [H-3]MK-801 or a decrease in [H-3]D-Asp binding in the basal ganglia in schizophrenia, the increased caudate AMPA binding observed here could reflect decreased cortical glutamatergic innervation of the caudate. Its implication for suicide is unclear. (C) 1997 Wiley-Liss, Inc. C1 NIMH,NEUROSCI CTR ST ELIZABETHS,DIRP,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. EMORY UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,ATLANTA,GA. NR 47 TC 74 Z9 75 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD NOV PY 1997 VL 27 IS 3 BP 168 EP 176 DI 10.1002/(SICI)1098-2396(199711)27:3<168::AID-SYN2>3.0.CO;2-B PG 9 WC Neurosciences SC Neurosciences & Neurology GA XZ358 UT WOS:A1997XZ35800002 PM 9329152 ER PT J AU Shaw, GM Velie, EM Schaffer, DM AF Shaw, GM Velie, EM Schaffer, DM TI Is dietary intake of methionine associated with a reduction in risk for neural tube defect-affected pregnancies? SO TERATOLOGY LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; METHYLENETETRAHYDROFOLATE REDUCTASE; SPINA-BIFIDA; RAT EMBRYOS; RECORDS; CLOSURE AB Results from experimental animals and other laboratory data have suggested a role for methionine, an essential amino acid, in normal closure of the neural tube. We hypothesized that women who had higher dietary intakes of methionine would be at lower risk for neural tube defect (NTD)-affected pregnancies. Data were derived from a population-based case-control study of fetuses and liveborn infants with NTDs among a 1989-1991 California birth cohort. Interviews, which included a 100-item food frequency questionnaire, were conducted with mothers of 424 NTD cases and 440 nonmalformed controls. Risk for having an NTD-affected pregnancy was estimated according to quartiles (established from intakes among control mothers) of average daily maternal dietary intake of methionine in the 3 months before conception. We observed an approximately 30-40% reduction in NTD-affected pregnancies among women whose average daily dietary intake of methionine was above the lowest quartile of intake (> 1,341.86 mg/day). These reductions in NTD risk were observed for both anencephaly and spina bifida; remained after adjustment for maternal race/ethnicity and education; and were observed irrespective of maternal level of folate intake. Although we were unable to establish whether the observed reductions in NTD risk were attributable to maternal periconceptional methionine intake or to another highly correlated nutrient, these data add to the growing body of evidence that maternal diet plays a role in neural tube closure. (C) 1997 Wiiey-Liss, Inc. C1 March Dimes Birth Defects Fdn, Calif Birth Defects Monitoring Program, Emeryville, CA 94608 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94611 USA. RP Shaw, GM (reprint author), March Dimes Birth Defects Fdn, Calif Birth Defects Monitoring Program, 1900 Powell St,Suite 1050, Emeryville, CA 94608 USA. NR 27 TC 45 Z9 45 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0040-3709 J9 TERATOLOGY JI Teratology PD NOV PY 1997 VL 56 IS 5 BP 295 EP 299 DI 10.1002/(SICI)1096-9926(199711)56:5<295::AID-TERA1>3.0.CO;2-X PG 5 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA YQ148 UT WOS:000071353300001 PM 9451752 ER PT J AU Peters, JM Taubeneck, MW Keen, CL Gonzalez, FJ AF Peters, JM Taubeneck, MW Keen, CL Gonzalez, FJ TI Di(2-ethylhexyl) phthalate induces a functional zinc deficiency during pregnancy and teratogenesis that is independent of peroxisome proliferator-activated receptor-alpha SO TERATOLOGY LA English DT Article ID HEPATIC METALLOTHIONEIN; DEVELOPMENTAL TOXICITY; ZN-65 DISTRIBUTION; FATTY-ACIDS; MICE; RAT; METABOLISM; INDUCTION; MECHANISMS; LIVER AB Di(2-ethylhexyl) phthalate (DEHP) is a peroxisome proliferator whose administration to rodents induces a pleiotropic response mediated by the peroxisome proliferator-activated receptor-alpha (PPAR alpha). The mechanisms underlying DEHP-induced reproductive toxicity and teratogenicity ave not well understood but could be the result of an alteration in gene expression by PPAR alpha. Additionally, phthalate exposure is known to impair fetal zinc (Zn) levels during pregnancy. In this work, we investigated whether the reproductive toxicity and teratogenicity of DEHP are mediated by PPAR alpha and whether the receptor influences maternal and/or embryonic Zn metabolism. Pregnant female mice, homozygous wild-type (+/+) or PPAR alpha-null (-/-), were intubated with either vehicle alone or 1,000 mg DEHP/kg body weight on gestation day (GD) 8 and 9. Pregnancy outcome was evaluated on GD10 and GD18 in two cohorts of animals. Compared to controls, DEHP administration resulted in maternal toxicity, embryo/fetal toxicity, and teratogenicity in both (+/+) and (-/-) mice. Maternal liver mRNA for cytochrome P-450 4A1 (CYP4A1) was higher in DEHP-treated (+/+) mice but not in DEHP-treated (-/-) mice on GD10, consistent with their respective phenotype. Maternal liver MT and Zn levels were significantly higher than in controls on GD10. In addition, embryonic Zn content was significantly lower in both genotypes treated with DEHP compared to controls. Results from this work show that DEHP-induced reproductive toxicity, teratogenicity, and altered Zn metabolism are not mediated through PPAR alpha-dependent mechanisms. In addition, this work suggests that DEHP-induced alterations in Zn metabolism contribute to the mechanisms underlying DEHP-induced reproductive toxicity and teratogenicity. (C) 1997 Wiley-Liss, Inc. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA. Univ Calif Davis, Dept Internal Med, Davis, CA 95616 USA. RP Peters, JM (reprint author), NCI, Lab Metab, NIH, Bldg 37,Room 3E-24, Bethesda, MD 20892 USA. RI Peters, Jeffrey/D-8847-2011 FU NICHD NIH HHS [HD26777, HD01743] NR 31 TC 57 Z9 60 U1 0 U2 8 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0040-3709 J9 TERATOLOGY JI Teratology PD NOV PY 1997 VL 56 IS 5 BP 311 EP 316 DI 10.1002/(SICI)1096-9926(199711)56:5<311::AID-TERA4>3.0.CO;2-# PG 6 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA YQ148 UT WOS:000071353300004 PM 9451755 ER PT J AU Sampson, PD Streissguth, AP Bookstein, FL Little, RE Clarren, SK Dehaene, P Hanson, JW Graham, JM AF Sampson, PD Streissguth, AP Bookstein, FL Little, RE Clarren, SK Dehaene, P Hanson, JW Graham, JM TI Incidence of fetal alcohol syndrome and prevalence of alcohol-related neurodevelopmental disorder SO TERATOLOGY LA English DT Article ID PRENATAL ALCOHOL; ECONOMIC-IMPACT; EXPOSURE; PREGNANCY; CONSUMPTION; ETHANOL; FAS; DIAGNOSIS; FREQUENCY; DEFICITS AB We critique published incidences for fetal alcohol syndrome (FAS) and present new estimates of the incidence of FAS and the prevalence of alcohol-related neurodevelopmental disorder (ARND). We first review criteria necessary for valid estimation of FAS incidence, Estimates for three population-based studies that best meet these criteria are reported with adjustment for underascertainment of highly exposed cases. As a result, in 1975 in Seattle, the incidence of FAS can be estimated as at least 2.8/1000 live births, and for 1979-81 in Cleveland, similar to 4.6/1,000. In Roubaix, France (for data covering periods from 1977-1990), the rate is between 1.3 and 4.8/1,000, depending on the severity of effects used as diagnostic criteria. Utilizing the longitudinal neurobehavioral database of the Seattle study, we propose an operationalization of the Institute of Medicine's recent definition of ARND and estimate its prevalence in Seattle for the period 1975-1981. The combined rate of FAS and ARND is thus estimated to be at least 9.1/1,000. This conservative rate-nearly one in every 100 live births-confirms the perception of many health professionals that fetal alcohol exposure is a serious problem. (C) 1997 Wiley-Liss, Inc. C1 Univ Washington, Dept Psychiat & Behav Sci, Fetal Alcohol & Drug Unit, Sch Med, Seattle, WA 98195 USA. Univ Washington, Dept Stat, Seattle, WA 98195 USA. Univ Michigan, Inst Gerontol, Ann Arbor, MI 48109 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Univ Washington, Div Congenital Defects, Sch Med, Seattle, WA 98195 USA. Ctr Hosp & Pouponniere Boucicaut, Unite Neonatol, Roubaix, France. NICHD, Ctr Res Mothers & Children, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Med,Cedars Sinai Med Ctr,Ahmanson Pediat Ctr, Med Genet Birth Defect Ctr,SHARE Child Disab Ctr, Steven Spielberg Pediat Res Ctr, Los Angeles, CA 90048 USA. RP Streissguth, AP (reprint author), Univ Washington, Dept Psychiat & Behav Sci, Fetal Alcohol & Drug Unit, Sch Med, Box 359112, Seattle, WA 98195 USA. RI Rohlf, F/A-8710-2008 FU NIAAA NIH HHS [AA01455-0-20] NR 61 TC 490 Z9 499 U1 4 U2 54 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0040-3709 J9 TERATOLOGY JI Teratology PD NOV PY 1997 VL 56 IS 5 BP 317 EP 326 DI 10.1002/(SICI)1096-9926(199711)56:5<317::AID-TERA5>3.0.CO;2-U PG 10 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA YQ148 UT WOS:000071353300005 PM 9451756 ER PT J AU vanWagtendonkdeLeeuw, AM denDaas, JHG Rall, WF AF vanWagtendonkdeLeeuw, AM denDaas, JHG Rall, WF TI Field trial to compare pregnancy rates of bovine embryo cryopreservation methods: Vitrification and one-step dilution versus slow freezing and three-step dilution SO THERIOGENOLOGY LA English DT Article DE bovine embryos; cryopreservation; embryo transfer; vitrification ID CATTLE EMBRYOS; GLYCEROL AB We designed and conducted a field trial to obtain accurate pregnancy rates of Day 7 bovine embryos after vitrification in PB1 containing 6.5 M glycerol and 6% BSA (w/v) and one-step dilution in 1 M sucrose compared with controlled slow freezing in 1.5 M glycerol and three-step dilution. Embryos were collected from superovulated donor cows, and Grade 1 and 2 morulae and blastocysts were randomly assigned to each cryopreservation treatment group. Dutch farmers were solicited to participate in the field trial by an advertisement that offered cryopreserved embryos at subsidized cost. Within a period of 11 wk, one of six technicians visited 150 farms. Standard nonsurgical methods were used to transfer a total of 728 cryopreserved embryos. Recipient cows, mainly multiparous and of various breeds, the so-called ''bottom-end'' of the national herd, received embryos either 6, 7 or 8 d after standing estrus during natural estrous cycles. We compiled a database on 22 factors that may influence establishment of pregnancy in order to check randomization of each factor over cryopreservation treatment groups and embryo transfer technicians and to perform the statistical tests. Overall pregnancy rates were 44.5% (n=393) for vitrified embryos and 45.1% (n=335) for slowly frozen embryos. Pregnancy rates were not significantly different (ANOVA, P=0.79 or Chi-square analysis, P=0.88). The registered data confirm that all factors were randomly distributed over cryopreservation methods and technicians. Technician was not a significant source of variation in pregnancy rate (analysis of variance, P=0.79). Although three technicians performed better with the one-step procedure:and the other three performed better using the three-step method, the interaction between the technician and cryopreservation method was not significant (Tukey's test for nonadditivity, P=0.13). Our results indicate that 1) vitrification and one-step dilution can be successfully used in the field without significant reduction in the pregnancy rate and 2) the pregnancy rate obtained using the ''bottom-end'' of the herd is satisfactory for practical application. (C) 1997 by Elsevier Science Inc. C1 NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BETHESDA,MD 20892. RP vanWagtendonkdeLeeuw, AM (reprint author), HOLLAND GENET,POSTBUS 5703,NL-6802 EB ARNHEM,NETHERLANDS. RI Rall, William/C-5104-2008 NR 23 TC 38 Z9 41 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0093-691X J9 THERIOGENOLOGY JI Theriogenology PD NOV PY 1997 VL 48 IS 7 BP 1071 EP 1084 DI 10.1016/S0093-691X(97)00340-3 PG 14 WC Reproductive Biology; Veterinary Sciences SC Reproductive Biology; Veterinary Sciences GA YB776 UT WOS:A1997YB77600001 PM 16728196 ER PT J AU Krutzsch, H Williams, SB McKeown, LP Gralnick, HR AF Krutzsch, H Williams, SB McKeown, LP Gralnick, HR TI Structure-function studies on the inhibition of binding of alpha-thrombin to platelet GpIb alpha by the peptide D-Y-Y-P-E and the artifactual inhibitory activity of C-terminal E in this peptide SO THROMBOSIS RESEARCH LA English DT Article DE alpha-thrombin; peptides; platelets C1 NIH, Warren Grant Magnuson Clin Ctr, Serv Hematol, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Pathol Lab, Bethesda, MD 20892 USA. RP Gralnick, HR (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Serv Hematol, Room 2C390, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD NOV 1 PY 1997 VL 88 IS 3 BP 333 EP 335 DI 10.1016/S0049-3848(97)00260-0 PG 3 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA ZA536 UT WOS:000072374100010 PM 9526954 ER PT J AU Lin, L Jin, L Kimura, A Carrington, M Mignot, E AF Lin, L Jin, L Kimura, A Carrington, M Mignot, E TI DQ microsatellite association studies in three ethnic groups SO TISSUE ANTIGENS LA English DT Article DE DQCAR; DQCARII; G51152; HLA; DQA1; DQB1; microsatellite marker; recombination; mutation rate ID LYMPHOBLASTOID CELL-LINES; LINKAGE DISEQUILIBRIUM; HLA-B; POLYMORPHISMS; GENES; POPULATIONS; MUTATIONS; EVOLUTION; ALLELES; SUSCEPTIBILITY AB Polymorphism at the level of three microsatellite markers (DQCAR, DQCARII, G51152) located in the HLA-DQ region was characterized in 78 10th International Histocompatibility Workshop B-cell lines, 718 random Japanese Asians, 99 Norwegian Caucasians and 95 New Guinean Aborigines with established HLA-DRB1, -DQA1 and -DQB1 typing. DQCAR, DQCARII, and G51152 result in 13, 13, and 11 alleles respectively. All three markers were in tight linkage disequilibrium with HLA-DRB1, -DQA1 and -DQB1. DRB1, DQA1, DQCARII, DQCAR, DQB1, and G51152 haplotypes could be defined for all subjects. In fact, DQ microsatellite typing data could predict DQA1 and DQB1 genotypes with high accuracy and may be used as a simple first pass HLA-DQ typing method. The haplotype data was also used to determine recombination in the DRB1-DQA1 (about 80 kb), DQA1-DQCARII (about 4.5 kb), DQCARII-DQCAR (about 7.5 kb), DQCAR-DQB1 (about 1-1.5 kb) and DQB1-G51152 (about 20-25 kb) genomic segments and the relative rate of slippage microsatellite mutations for DQCAR, DQCARII, and G51152. This led us to conclude that recombination is more frequent in the DRB1-DQA1 and DQCAR-DQCARII segments, thus suggesting cross-overs within small genomic segments are not proportional to genetic distance. We also observed that DQCAR had a higher mutation rate than DQCARII or G51152 and that 1 or 2 CA slippage mutations were arising more frequently from large size microsatellite alleles. C1 UNIV TEXAS,CTR HUMAN GENET,HOUSTON,TX. TOKYO MED & DENT UNIV,TOKYO 113,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,FREDERICK,MD 21701. RP Lin, L (reprint author), STANFORD UNIV,MED CTR,DEPT PSYCHIAT,CTR NAROLEPSY,701 WELCH RD,SUITE 2226,PALO ALTO,CA 94301, USA. RI Jin, Li/C-1468-2009 OI Jin, Li/0000-0002-4546-2415 FU NINDS NIH HHS [NS/MH33797, NS23724] NR 45 TC 42 Z9 43 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD NOV PY 1997 VL 50 IS 5 BP 507 EP 520 DI 10.1111/j.1399-0039.1997.tb02907.x PG 14 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA YC439 UT WOS:A1997YC43900012 PM 9389326 ER PT J AU Dunnick, JK Hardisty, JE Herbert, RA Seely, JC Furedi-Machacek, EM Foley, JF Lacks, GD Stasiewicz, S French, JE AF Dunnick, JK Hardisty, JE Herbert, RA Seely, JC Furedi-Machacek, EM Foley, JF Lacks, GD Stasiewicz, S French, JE TI Phenolphthalein induces thymic lymphomas accompanied by loss of the p53 wild type allele in heterozygous p53-deficient (+/-) mice SO TOXICOLOGIC PATHOLOGY LA English DT Article DE p53; phenolphthalein; p53-deficient (+/-) mice; thymic lymphoma; carcinogenesis ID TUMOR-SUPPRESSOR GENE; ANIMAL CARCINOGENICITY; INDUCED TUMORIGENESIS; BILIARY-EXCRETION; B6C3F1 MICE; MUTATIONS; CANCER; RAS; TRANSFORMATION; ACTIVATION AB Epidemiology studies have indicated that many human cancers are influenced by environmental factors. Genetically altered mouse model systems offer us the opportunity to study the interaction of chemicals with genetic predisposition to cancer. Using the heterozygous p53-deficient (+/-) mouse, an animal model carrying one wild type p53 gene and one p53 null allele, we studied the effects of phenolphthalein on tumor induction and p53 gene alterations. Earlier studies showed that phenolphthalein caused carcinogenic effects in Fisher 344 rats and B6C3F(1) mice after a 2-yr dosing period (Dunnick and Hailey, Cancer Res. 56: 4922-4926, 1996). The p53 (+/-) mice received phenolphthalein in the feed at concentrations of 200, 375, 750, 3,000, or 12,000 ppm (approximately 43, 84, 174, 689, or 2,375 mg/kg body weight/day or 129, 252, 522, 2,867, or 7,128 mg/m(2) body surface area/day) for up to 6 mo. A target organ cancer site that accumulated p53 protein in the B6C3F(1) mouse (i.e., thymic lymphoma) was also a target site for cancer in the p53 (+/-) mouse. In the p53 (+/-) mouse, treatment-related atypical hyperplasia and malignant lymphoma of thymic origin were seen in the control and dosed groups at a combined incidence of 0, 5, 5, 25, 100, and 95%, respectively. Twenty-one of the thymic lymphomas were examined for p53 gene changes, and all showed loss of the p53 wild type allele. Chemical-induced ovarian tumors in the B6C3F(1) mouse showed no evidence for p53 protein accumulation and did not occur in the p53 (+/-) mouse. The p53-deficient (+/-) mouse model responded to phenolphthalein treatment with a carcinogenic response in the thymus after only 4 mo of dosing. This carcinogenic response took 2 yr to develop in the conventional B6C3F(1) mouse bioassay. The p53-deficient (+/-) mouse is an important model for identifying a carcinogenic response after short-term (<6 mo) exposures. Our studies show that exposure to phenolphthalein combined with a genetic predisposition to cancer can potentiate the carcinogenic process and cause p53 gene alterations, a gene alteration found in many human cancers. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Dunnick, JK (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. FU NIEHS NIH HHS [N01-ES-15321] NR 52 TC 65 Z9 66 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD NOV-DEC PY 1997 VL 25 IS 6 BP 533 EP 540 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA YP699 UT WOS:000071305100001 PM 9437796 ER PT J AU Dunnick, JK Heath, JE Farnell, DR Prejean, JD Haseman, JK Elwell, MR AF Dunnick, JK Heath, JE Farnell, DR Prejean, JD Haseman, JK Elwell, MR TI Carcinogenic activity of the flame retardant, 2,2-bis(bromomethyl)-1,3-propanediol in rodents, and comparison with the carcinogenicity of other NTP brominated chemicals SO TOXICOLOGIC PATHOLOGY LA English DT Article DE brominated chemicals; 2,2-bis(bromomethyl)-1,3-propanediol; carcinogenesis ID ANIMAL CARCINOGENICITY AB Several brominated chemicals have been shown to be multisite-multispecies carcinogens in laboratory animals, and in this paper we report that the flame retardant, 2,2-bis(bromomethyl)-1,3-propanediol (BMP) is also a multisite carcinogen in both sexes of Fischer 344 rats and B6C3F(1) mice. BMP was administered continuously in the diet for up to 2 yr to rats at doses of 0, 2,500, 5,000, or 10,000 ppm and to mice at doses of 0, 312, 625, or 1,250 ppm. Interim groups of rats were examined at 15 mo. An additional recovery group of male rats received the chemical for 3 mo at 20,000 ppm in the feed, and then the control diet for the remainder of the study. Chemical exposure caused neoplasms of the skin, subcutaneous tissue, mammary gland, Zymbal's gland, oral cavity, esophagus, forestomach, small intestine, large intestine, mesothelium, kidney, urinary bladder, lung, thyroid gland, seminal vesicle, hematopoietic system, and pancreas in the male rat; mammary gland, oral cavity, esophagus, and thyroid gland in the female rat; lung, kidney, and Harderian gland in male mice; and subcutaneous tissue, lung, and Harderian gland in the female mouse. The recovery group of male rats presented with the same spectrum of treatment-related neoplasms as in the core study. In this recovery group, BMP (at 20,000 ppm) caused irreversible effects at numerous sites after 90 days of exposure that was not detectable by histologic examination, but without further exposure resulted in carcinogenic responses at 2 yr. BMP is mutagenic in the salmonella test, but it was not determined if the BMP-induced effects that eventually lead to development of neoplasms at multiple sites are the same in both species and in all organ systems affected. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Dunnick, JK (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 17 TC 21 Z9 21 U1 0 U2 2 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD NOV-DEC PY 1997 VL 25 IS 6 BP 541 EP 548 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA YP699 UT WOS:000071305100002 PM 9437797 ER PT J AU Ward, JM AF Ward, JM TI Commentary - Helicobacter infections of rodents and carcinogenesis bioassays SO TOXICOLOGIC PATHOLOGY LA English DT Editorial Material C1 NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Ward, JM (reprint author), NCI, Frederick Canc Res & Dev Ctr, Fairview 201, Frederick, MD 21702 USA. NR 0 TC 1 Z9 2 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD NOV-DEC PY 1997 VL 25 IS 6 BP 590 EP 590 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA YP699 UT WOS:000071305100008 PM 9437803 ER PT J AU Nyska, A Maronpot, RR Eldridge, SR Haseman, JK Hailey, JR AF Nyska, A Maronpot, RR Eldridge, SR Haseman, JK Hailey, JR TI Alteration in cell kinetics in control B6C3F(1) mice infected with Helicobacter hepaticus SO TOXICOLOGIC PATHOLOGY LA English DT Article DE liver neoplasia; bioassays; hepatitis; PCNA; apoptosis; immunohistochemistry; cell proliferation ID CHRONIC ACTIVE HEPATITIS; HEPATOCELLULAR PROLIFERATION; NUCLEAR ANTIGEN; APOPTOSIS; IDENTIFICATION; CARCINOGENESIS; NEOPLASIA; MARKER; ASSAY; PCR AB The discovery of Helicobacter hepaticus infection, H. hepaticus hepatitis, and increased incidence of liver tumors in control males from several recent National Toxicology Program B6C3F(1) mouse carcinogenicity bioassays raised questions regarding the suitability of these bioassays for hazard identification. The purpose of this study was to determine if changes in cell proliferation and death at terminal sacrifice might be linked to the increased liver tumor incidences among control males. In control males, enhanced rates of hepatocyte proliferation, as assessed by immunostaining for proliferating cell nuclear antigen (PCNA), and apoptosis, as assessed from hematoxylin and eosin- and TUNEL-stained preparations, were seen in 3 bioassays with H. hepaticus hepatitis. One bioassay with H. hepaticus infection without attendant hepatitis and one bioassay without H. hepaticus or hepatitis did not have elevated rates of hepatocyte proliferation or apoptosis. There was no significant effect on PCNA cell proliferation indices or apoptosis in females. The present findings are indicative of a clear association between the presence of H. hepaticus infection with attendant hepatitis, increased cell proliferation and apoptosis, and increased incidences of hepatocellular neoplasia in males but not in females. Thus, the interpretation of liver tumor responses in H. hepaticus-infected studies is considered to be confounded in male mice. The lack of enhanced cell proliferation or hepatocellular neoplasia in control females suggests that bioassay results from females are valid for hazard identification. Furthermore, the absence of enhanced cell proliferation in lungs and kidneys of male and females suggests that neoplastic effects at these sites are not exacerbated by H. hepaticus infection. C1 NIEHS, Natl Toxicol Program, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. RP Maronpot, RR (reprint author), NIEHS, Natl Toxicol Program, Lab Expt Pathol, Mail Drop B3-06,POB 12233, Res Triangle Pk, NC 27709 USA. NR 32 TC 14 Z9 16 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD NOV-DEC PY 1997 VL 25 IS 6 BP 591 EP 596 PG 6 WC Pathology; Toxicology SC Pathology; Toxicology GA YP699 UT WOS:000071305100009 PM 9437804 ER PT J AU Diwan, BA Ward, JM Ramljak, D Anderson, LM AF Diwan, BA Ward, JM Ramljak, D Anderson, LM TI Promotion by Helicobacter hepaticus-induced hepatitis of hepatic tumors initiated by N-nitrosodimethylamine in male A/JCr mice SO TOXICOLOGIC PATHOLOGY LA English DT Article DE Helicobacter; hepatitis; N-nitrosodimethylamine; initiation; promotion; cell proliferation; cell cycle; cyclin D ID CHRONIC ACTIVE HEPATITIS; CYCLIN D1; LIVER-TUMORS; MOUSE SKIN; INDUCTION; CARCINOGENESIS; PROGRESSION; EXPRESSION; INFECTION; LUNG AB A new murine Helicobacter species, Helicobacter hepaticus, infects the livers of mice, causing a progressive chronic active hepatitis culminating in hepatocellular tumors. To examine the role of chronic H. hepaticus infection in carcinogenesis, H. hepaticus-infected male infant mice of A/JCr strain were given a single ip dose of N-nitrosodimethylamine (NDMA). Noninfected A/J mice similarly treated with NDMA served as controls. The effect of hepatitis induced by H. hepaticus was studied for 64 wk. At 31-36 wk, the incidence of hepatocellular adenomas in infected mice was significantly higher than in noninfected mice (82 vs 52%; p = 0.05). The multiplicity of hepatocellular tumors was also significantly higher in infected mice compared to noninfected mice (3.2 +/- 0.09 vs 0.09 +/- 0.2; p = 0.03). At 51-64 wk, many (10/18) infected mice developed hepatocellular carcinomas while only 2 of 19 control mice developed such tumors (p = 0.005). Overexpression of cyclin D was observed in hepatocytes as well as adenomas induced by NDMA in H. hepaticus-infected mice, suggesting its role in inflammation, abnormal cell growth, and early neoplasia. High molecular weight keratins were highly expressed in hyperplastic oval cells in hepatitis and in liver tumors in mice with hepatitis, establishing a reliable marker for oval cells in formalin-fixed, paraffin-embedded tissue. Thus, chronic H. hepaticus infection significantly stimulated cyclin D expression, accelerated the development of liver tumors, increased the multiplicity of such lesions, and enhanced the progression of benign to malignant tumors. C1 NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Diwan, BA (reprint author), NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Bldg 538,Room 205I, Frederick, MD 21702 USA. NR 40 TC 33 Z9 35 U1 0 U2 1 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD NOV-DEC PY 1997 VL 25 IS 6 BP 597 EP 605 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA YP699 UT WOS:000071305100010 PM 9437805 ER PT J AU Rodman, LE Farnell, DR Coyne, JM Allan, PW Hill, DL Duncan, KLK Tomaszewski, JE Smith, AC Page, JG AF Rodman, LE Farnell, DR Coyne, JM Allan, PW Hill, DL Duncan, KLK Tomaszewski, JE Smith, AC Page, JG TI Toxicity of cordycepin in combination with the adenosine deaminase inhibitor 2'-deoxycoformycin in beagle dogs SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID HAIRY-CELL LEUKEMIA; TERMINAL TRANSFERASE; BIOLOGICAL-ACTIVITY; PENTOSTATIN; DEOXYCOFORMYCIN; ENHANCEMENT; ANALOGS AB For 3 consecutive days, the nucleoside cordycepin (3'-deoxyadenosine) was administered as 1-hr iv infusions (0, 1, 4, 8, 10, or 20 mg/kg/day) to dogs. These doses were given 1 hr after a bolus iv injection (0.25 mg/kg/day) of 2'-deoxycoformycin (dCF), a potent inhibitor of adenosine deaminase. The hypothesis was that dCF would affect the toxicity of cordycepin. Plasma adenosine deaminase activity was strongly inhibited during the dose period and for 5 days following the final dose of dCF. Dogs given cordycepin alone showed no drug-related toxicities. In dogs given only dCF, drug-related toxicity to lymphoid tissue (lymphopenia and thymus lymphoid depletion), thrombocytopenia, and decreases in food consumption were observed. Cordycepin in combination with dCF produced symptoms associated with severe gastrointestinal toxicity (decreased body weights, emesis, diarrhea, decreased food consumption, and necrosis of the gastrointestinal tract) and bone marrow toxicity (lymphopenia, thrombocytopenia, and depletion of hematopoietic cells). The gastrointestinal tract and bone marrow were sites associated with dose-limiting toxicities. In surviving dogs, most of the effects were reversible by Day 30. The maximum tolerated dose of cordycepin administered in combination with dCF was 8 mg/kg/day (160 mg/m(2)/day) given daily for 3 days. (C) 1997 Academic Press. C1 NCI,BETHESDA,MD 20892. RP Rodman, LE (reprint author), SO RES INST,BIRMINGHAM,AL 35255, USA. RI Duncan, Kimberly /C-3655-2013 FU NCI NIH HHS [N01-CM-37835, N01-CM-57202] NR 30 TC 23 Z9 24 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV PY 1997 VL 147 IS 1 BP 39 EP 45 DI 10.1006/taap.1997.8264 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA YE974 UT WOS:A1997YE97400005 PM 9356305 ER PT J AU Blumenthal, GM Kohn, MC Portier, CJ AF Blumenthal, GM Kohn, MC Portier, CJ TI A mathematical model of production, distribution, and metabolism of melatonin in mammalian systems SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID SEROTONIN N-ACETYLTRANSFERASE; BLOOD PARTITION-COEFFICIENTS; RAT PINEAL-GLAND; ORGANIC-CHEMICALS; PLASMA MELATONIN; RECEPTOR; LIGHT; EXPRESSION; MECHANISM; ALGORITHM AB Melatonin is a neuroendocrine hormone which is currently receiving considerable attention as a treatment for jet lag, a treatment for insomnia and, by some, a possible ''magic bullet'' for delaying the effects of aging and preventing cancer. Production of melatonin is focused primarily in the pineal gland with very wide daily shifts in production controlled by the day/night cycle. The potential for increased disease as a consequence of lower or higher than average production of this hormone has not been well studied, although potential environmental agents may modulate circulating levels (e.g., electric and magnetic fields). In this manuscript, a physiologically realistic mathematical model for the production, distribution, and metabolism of melatonin is developed as a precursor to a future study of the role of chemicals and environmental agents in altering this system. Values for key aspects of the system (e.g., diurnal rates of production of the hormone in the pineal gland) were obtained from the literature and the model was validated against data on circulating levels. The mathematical equations and model parameters are presented. (C) 1997 Academic Press. RP Blumenthal, GM (reprint author), NATL INST ENVIRONM HLTH SCI, LAB COMPUTAT BIOL & RISK ANAL, POB 12233, RES TRIANGLE PK, NC 27709 USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 33 TC 8 Z9 10 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV PY 1997 VL 147 IS 1 BP 83 EP 92 DI 10.1006/taap.1997.8247 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA YE974 UT WOS:A1997YE97400010 PM 9356310 ER PT J AU Morozov, V Mushegian, AR Koonin, EV Bork, P AF Morozov, V Mushegian, AR Koonin, EV Bork, P TI A putative nucleic acid-binding domain in Bloom's and Werner's syndrome helicases SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID SYNDROME GENE; MUTATIONS; INTERACTS; CLONING; HOMOLOG; RECQ; SGS1 C1 SEQUANA THERAPEUT INC,LA JOLLA,CA 92037. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NIH,BETHESDA,MD 20894. EUROPEAN MOL BIOL LAB,D-69012 HEIDELBERG,GERMANY. MAX DELBRUCK CTR MOL MED,D-13189 BERLIN,GERMANY. RP Morozov, V (reprint author), BIOSCI AG,LION,D-69120 HEIDELBERG,GERMANY. RI Bork, Peer/F-1813-2013; OI Bork, Peer/0000-0002-2627-833X; Mushegian, Arcady/0000-0002-6809-9225 NR 22 TC 118 Z9 119 U1 1 U2 1 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 NOV PY 1997 VL 22 IS 11 BP 417 EP 418 DI 10.1016/S0968-0004(97)01128-6 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YG388 UT WOS:A1997YG38800003 PM 9397680 ER PT J AU Kass, SU Pruss, D Wolffe, AP AF Kass, SU Pruss, D Wolffe, AP TI How does DNA methylation repress transcription? SO TRENDS IN GENETICS LA English DT Review ID NEWLY REPLICATED CHROMATIN; CPG METHYLATION; CHROMOSOMAL PROTEIN; MAMMALIAN NUCLEI; XIST EXPRESSION; GENE-EXPRESSION; BINDING-PROTEIN; HISTONE H1; DE-NOVO; METHYLTRANSFERASE AB DNA methylation has an essential regulatory function in mammalian development, serving to repress nontranscribed genes stably in differentiated adult somatic cells. Recent data implicate transcriptional repressors specific for methylated DNA and chromatin assembly in this global control of gene activity. The assembly of specialized nucleosomal structures on methylated DNA helps to explain the capacity of methylated DNA segments to silence transcription more effectively than conventional chromatin, Specialized nucleosomes also provide a potential molecular mechanism for the stable propagation of DNA methylation-dependent transcriptional silencing through cell division. RP Kass, SU (reprint author), NICHHD,MOL EMBRYOL LAB,NIH,BLDG 18T,ROOM 106,BETHESDA,MD 20892, USA. NR 55 TC 376 Z9 387 U1 2 U2 19 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD NOV PY 1997 VL 13 IS 11 BP 444 EP 449 DI 10.1016/S0168-9525(97)01268-7 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA YF592 UT WOS:A1997YF59200008 PM 9385841 ER PT J AU Jones, JA Nguyen, A Straub, M Leidich, RB Veech, RL Wolf, S AF Jones, JA Nguyen, A Straub, M Leidich, RB Veech, RL Wolf, S TI Use of DHEA in a patient with advanced prostate cancer: A case report and review SO UROLOGY LA English DT Article ID DOSE MEDROXYPROGESTERONE ACETATE; ADRENAL ANDROGENS; DEHYDROEPIANDROSTERONE; INHIBITION; DEOXYRIBONUCLEOSIDES; CARCINOMA; REVERSAL; SULFATE; GROWTH; CELLS AB Dehydroepiandrosterone (DHEA) is being evaluated in the basic science laboratories as a potential treatment for adenocarcinomas, with some initial promise for success. However DHEA can be metabolically converted to androgenic compounds, possessing unwanted side effects. A patient with advanced prostate cancer with progressive symptomatology was treated with DHEA after other treatment regimens failed, Many of his symptoms improved on DHEA therapy, but his cancer also flared dramatically during treatment. His previous hormonally unresponsive cancer subsequently responded transiently to third-line hormonal therapy with diethylstilbestrol (DES). Adrenal precursor molecules such as DHEA may have significant therapeutic benefits in a number of diseases of the elderly, however their utility may be limited by potential androgenic side effects including endocrine epithelial cell growth. The development of analogue compounds with less conversion to androgenic metabolites should be considered, as molecules such as DHEA are more widely tested and utilized clinically. (C) 1997, Elsevier Science Inc. All rights reserved. C1 TEXAS TECH UNIV,HLTH SCI CTR,LUBBOCK,TX 79430. NIAAA,METAB & MOL BIOL LAB,BETHESDA,MD. TEMPLE UNIV,SCH MED,PHILADELPHIA,PA 19122. NR 31 TC 20 Z9 20 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 NOV PY 1997 VL 50 IS 5 BP 784 EP 788 DI 10.1016/S0090-4295(97)00395-6 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA YG346 UT WOS:A1997YG34600027 PM 9372895 ER PT J AU FernandezSalguero, PM Ward, JM Sundberg, JP Gonzalez, FJ AF FernandezSalguero, PM Ward, JM Sundberg, JP Gonzalez, FJ TI Lesions of aryl-hydrocarbon receptor-deficient mice SO VETERINARY PATHOLOGY LA English DT Article DE aryl-hydrocarbon receptor; cardiomyopathy; gastric polyps; immunodeficiency ID NORMAL HUMAN KERATINOCYTES; AH-RECEPTOR; TRANSFORMING GROWTH-FACTOR-BETA-1; HELICOBACTER-HEPATICUS; DIOXIN RECEPTOR; EXPRESSION; CLONING; GENES; TRANSCRIPTION; ACTIVATION AB We have analyzed the possible role of the aryl-hydrocarbon receptor (AHR) in the aging process of mice using a homozygous null mouse (Ahr-/-) line as a model. We studied 52 male and female Ahr-/- mice aged from 6-13 months. Forty-six percent died or were ill by 13 months of age. Ahr-/- mice developed age-related lesions in several organs, some of which were apparent after only 9 months of age. Cardiovascular alterations included cardiomyopathy (100%) with hypertrophy and focal fibrosis. Vascular hypertrophy and mild fibrosis were found in the portal areas of the liver (81%), and vascular hypertrophy and mineralization were common in the uterus (70%). Gastric hyperplasia that progressed with age into polyps was evident in the pylorus of 71% of the mice over 9 months of age. Ahr-/- mice had T-cell deficiency in their spleens but not in other lymphoid organs. The immune system deficiency described previously could be the ori,ain for the rectal prolapse found in 48% of the null mice, associated with Helicobacter hepaticus infection. In the dorsal skin (53% incidence), severe, localized, interfollicular and follicular epidermal hyperplasia, with hyperkeratosis and acanthosis, and marked dermal fibrosis, associated with the presence of anagenic hair follicles, were also evident. None of these lesions were found in 42 control (Ahr +/+ or +/-) mice of similar ages. These observations suggest that the AHR protein, in the absence of an apparent exogenous (xenobiotic) ligand, plays an important role in physiology and homeostasis in major organs in mice, and further supports an evolutionary conserved role for this transcription factor. C1 NCI,FREDERICK CANC RES & DEV CTR,VET & TUMOR PATHOL SECT,ANIM SCI BRANCH,NIH,FREDERICK,MD 21702. JACKSON LAB,BAR HARBOR,ME 04609. NCI,LAB METAB,NIH,BETHESDA,MD 20892. OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027 FU NCI NIH HHS [CA 34196]; NCRR NIH HHS [RR 08911] NR 37 TC 188 Z9 195 U1 2 U2 3 PU AMER COLL VET PATHOLOGIST PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 SN 0300-9858 J9 VET PATHOL JI Vet. Pathol. PD NOV PY 1997 VL 34 IS 6 BP 605 EP 614 PG 10 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA YG726 UT WOS:A1997YG72600009 PM 9396142 ER PT J AU Mavromatis, KO Jones, DL Mukherjee, R Yee, C Grace, M Munger, K AF Mavromatis, KO Jones, DL Mukherjee, R Yee, C Grace, M Munger, K TI The carboxyl-terminal zinc-binding domain of the human papillomavirus E7 protein can be functionally replaced by the homologous sequences of the E6 protein SO VIRUS RESEARCH LA English DT Article DE retinoblastoma tumor suppressor protein; E2F; human papillomavirus; E6; E7 ID RETINOBLASTOMA GENE-PRODUCT; TUMOR SUPPRESSOR PROTEIN; TYPE-16 E7; TRANSCRIPTION FACTOR; HPV E6; ONCOPROTEIN; P53; DEGRADATION; E2F; TRANSACTIVATION AB The carboxyl-terminus is necessary for the functional and structural integrity of the human papillomavirus (HPV E7 oncoprotein, Since many mutations in this domain of E7 result in the formation of unstable proteins, we have evaluated the importance of this region by replacing it with structurally related domains derived from HPV E6 proteins. Biological analysis of these mutant chimeric E7/E6 proteins showed that they retained E7-specific biological activities including cooperation with the ras oncogene to transform primary baby rat kidney cells and transcriptional activation of an E2F responsive reporter plasmid. One of the chimeric proteins was impaired in its ability to physically disrupt pRB/E2F complexes in vitro suggesting that there are defined molecular determinants in the carboxyl-terminus of E7 for this activity. In contrast, none of these proteins exhibited E6-like properties including binding to p53 and/or degradation of associated proteins. (C) 1997 Elsevier Science B.V. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NCI, Tumor Virus Biol Lab, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA 02115 USA. NCI, Dermatol Branch, Bethesda, MD 20892 USA. RP Munger, K (reprint author), Harvard Univ, Sch Med, Dept Pathol, Goldenson Bldg,Room 113A,200 Longwood Ave, Boston, MA 02115 USA. OI Munger, Karl/0000-0003-3288-9935 NR 35 TC 10 Z9 11 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD NOV PY 1997 VL 52 IS 1 BP 109 EP 118 DI 10.1016/S0168-1702(97)00090-7 PG 10 WC Virology SC Virology GA YM596 UT WOS:000071080600010 PM 9453149 ER PT J AU Joseph, JS Victor, JD Optican, LM AF Joseph, JS Victor, JD Optican, LM TI Scaling effects in the perception of higher-order spatial correlations SO VISION RESEARCH LA English DT Article DE texture discrimination; higher-order correlations; scale invariance; absolute efficiency ID TRIPLE CORRELATION UNIQUENESS; FREQUENCY DISCRIMINATION; TEXTURE-DISCRIMINATION; JULESZ CONJECTURE; STATISTICS; PHASE AB Human texture discrimination depends both on spatial-frequency content and on higher-order or multi-point correlations, Spatial-frequency discrimination exhibits a high degree of scale invariance over a range of several octaves, but the scaling behavior of sensitivity to higher-order correlation structure is unknown, We explored the scale dependence of texture discrimination for image ensembles which shared the same power spectrum, but differed in their higher-order correlations, Literally scaling the ensembles so that they occupy larger retinal regions results in discrimination performance that is largely independent of scale over a 3 octave range, Holding the display size constant and scaling the texture being sampled within the display over the same range produces performance that varies with scale appreciably, The ideal observer performance is computed, and the absolute efficiency is seen to be quite small, on the order of 10(-2)-10(-1), As the texture is scaled down, increasing the number of checks within the fixed display size, performance increases while the efficiency decreases, These dependencies remain when the stimulus onset asynchrony is increased from 50 to 500 msec, We created sets of textures which varied both in check number and correlation strength, for which ideal observer performance was equated, For the human observers, efficiency was significantly higher for textures with higher correlation strength, but fewer checks, These results are consistent with a model in which a fixed number of checks is processed in a scale-invariant manner, while the remainder of the display is processed much less efficiently. (C) 1997 Elsevier Science Ltd. C1 NEI,SENSORIMOTOR RES LAB,NIH,BETHESDA,MD 20892. CORNELL UNIV,COLL MED,DEPT NEUROL & NEUROSCI,NEW YORK,NY 10021. RI Victor, Jonathan/D-2931-2009 FU NEI NIH HHS [F32-EY06531, EY7977] NR 23 TC 8 Z9 8 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0042-6989 J9 VISION RES JI Vision Res. PD NOV PY 1997 VL 37 IS 22 BP 3097 EP 3107 DI 10.1016/S0042-6989(97)00068-0 PG 11 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA YC483 UT WOS:A1997YC48300004 PM 9463692 ER PT J AU Parvari, R Lei, KJ Bashan, N Hershkovitz, E Korman, SH Barash, V LermanSagie, T Mandel, H Chou, JY Moses, SW AF Parvari, R Lei, KJ Bashan, N Hershkovitz, E Korman, SH Barash, V LermanSagie, T Mandel, H Chou, JY Moses, SW TI Glycogen storage disease type 1a in Israel: Biochemical, clinical, and mutational studies SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE glycogen storage disease type 1a; Israeli mutations; Ashkenazi Jews; Muslim Arabs ID GLUCOSE-6-PHOSPHATASE GENE; JEWISH AB Glycogen storage disease type 1a (von Gierke disease, GSD 1a) is caused by the deficiency of microsomal glucose-6-phosphatase (G6Pase) activity which catalyzes the final common step of glycogenolysis and gluconeogenesis. The recent cloning of the G6Pase cDNA and characterization of the human G6Pase gene enabled the characterization of the mutations causing GSD 1a. This, in turn, allows the introduction of a noninvasive DNA-based diagnosis that provides reliable carrier testing and prenatal diagnosis, In this study, we report the biochemical and clinical characteristics as well as mutational analyses of 12 Israeli GSD 1a patients of different families, who represent most GSD 1a patients in Israel. The mutations, G6Pase activity, and glycogen content of 7 of these patients were reported previously, The biochemical data and clinical findings of all patients were similar and compatible with those described, in other reports, All 9 Jewish patients, as well as one Muslim Arab patient, presented the R83C mutation, Two Muslim Arab patients had the V166G mutation which was not found in other patients' populations, The V166G mutation, which was introduced into the G6Pase cDNA by site-directed mutagenesis following transient expression in COS-1 cells, was shown to cause complete inactivation of the G6Pase. The characterization of all GSD 1a mutations in the Israeli population lends itself to carrier testing in these families as well. as to prenatal diagnosis, which was carried out in 2 families, Since all Ashkenazi Jewish patients harbor the same mutation, our study suggests that DNA-based diagnosis may be used as an initial diagnostic step in Ashkenazi Jews suspected of having GSD 1a, thereby avoiding liver biopsy. (C) 1997 Wiley-Liss, Inc. C1 NICHHD,HERITABLE DISORDERS BRANCH,NIH,BETHESDA,MD. BEN GURION UNIV NEGEV,FAC HLTH SCI,SOROKA MED CTR,DEPT BIOCHEM,IL-84101 BEER SHEVA,ISRAEL. BEN GURION UNIV NEGEV,FAC HLTH SCI,SOROKA MED CTR,DEPT PEDIAT,IL-84101 BEER SHEVA,ISRAEL. HEBREW UNIV JERUSALEM,DEPT PEDIAT,MOL BIOL UNIT,HADASSAH MED CTR,JERUSALEM,ISRAEL. HEBREW UNIV JERUSALEM,DEPT CLIN BIOCHEM,MOL BIOL UNIT,HADASSAH MED CTR,JERUSALEM,ISRAEL. TEL AVIV UNIV,SACKLER SCH MED,TEL AVIV MED CTR,DANA CHILDRENS HOSP,NEUROL UNIT,IL-69978 TEL AVIV,ISRAEL. TECHNION ISRAEL INST TECHNOL,RAMBAM MED CTR,SCH MED,DEPT PEDIAT,HAIFA,ISRAEL. RP Parvari, R (reprint author), BEN GURION UNIV NEGEV,FAC HLTH SCI,SOROKA MED CTR,GENET INST,IL-84101 BEER SHEVA,ISRAEL. RI Hershkovitz, Eli/F-1922-2012 NR 14 TC 30 Z9 31 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 31 PY 1997 VL 72 IS 3 BP 286 EP 290 DI 10.1002/(SICI)1096-8628(19971031)72:3<286::AID-AJMG6>3.0.CO;2-P PG 7 WC Genetics & Heredity SC Genetics & Heredity GA XZ502 UT WOS:A1997XZ50200006 PM 9332655 ER PT J AU Smith, CL Hager, GL AF Smith, CL Hager, GL TI Transcriptional regulation of mammalian genes in vivo - A tale of two templates SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID TUMOR VIRUS PROMOTER; HUMAN ALPHA-1-ANTITRYPSIN GENE; BETA-GLOBIN LOCUS; MMTV PROMOTER; CHROMATIN STRUCTURE; RETINOIC ACID; CELL HYBRIDS; IN-VIVO; DNA; ACTIVATION C1 NCI,LAB RECEPTOR BIOL & GENE EXPRESS,NIH,BETHESDA,MD 20892. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 47 TC 203 Z9 205 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 OCT 31 PY 1997 VL 272 IS 44 BP 27493 EP 27496 DI 10.1074/jbc.272.44.27493 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YD473 UT WOS:A1997YD47300001 PM 9346875 ER PT J AU Butler, AA Blakesley, VA Koval, A DeJong, R Groffen, J LeRoith, D AF Butler, AA Blakesley, VA Koval, A DeJong, R Groffen, J LeRoith, D TI In vivo regulation of CrkII and CrkL proto-oncogenes in the uterus by insulin-like growth factor-I - Differential effects on tyrosine phosphorylation and association with paxillin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID C-CRK; V-CRK; RECEPTOR SUBSTRATE-1; SIGNALING PATHWAYS; DEPENDENT MANNER; ADAPTER PROTEINS; ENDOGENOUS CRK; BINDING; PRODUCT; CELLS AB Changes in CrkII and CrkL phosphorylation are associated with insulin-like growth factor receptor activation in cultured cells. We examined whether similar changes also occur following administration of recombinant human insulin-like growth factor-I to the intact animal. In female rats starved overnight, CrkL phosphorylation was significantly increased 12 min after insulin-like growth factor-I administration. Tyrosine phosphorylation of CrkII was not detectable in either control or treated animals. Paxillin, a 65-70-kDa phosphoprotein containing high affinity binding sites common for the Src homology 2 (SH2) domains of CrkII and CrkL, was observed in both CrkII and CrkL immunoprecipitates. Insulin-like growth factor-I treatment stimulated the association of CrkII with paxillin. In contrast, the same treatment resulted in the dissociation of the CrkL-paxillin complex. Similar effects of insulin-like growth factor-I treatment on the association of CrkL with tyrosine phosphorylated paxillin were observed in fibroblasts overexpressing CrkL. This study demonstrates that the activation of the insulin-like growth factor-I receptor induces changes in the tyrosine phosphorylation and protein-protein interactions of the Crk proteins in vivo. The different responses of CrkL and CrkII to insulin-like growth factor-I receptor activation suggest distinct roles for these two adapter proteins in signal transduction. C1 NIDDK,DIABET BRANCH,NIH,BETHESDA,MD 20892. CHILDRENS HOSP,DEPT PATHOL,SECT MOL CARCINOGENESIS,LOS ANGELES,CA 90027. NR 32 TC 28 Z9 28 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 OCT 31 PY 1997 VL 272 IS 44 BP 27660 EP 27664 DI 10.1074/jbc.272.44.27660 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YD473 UT WOS:A1997YD47300031 PM 9346905 ER PT J AU Huang, CS Ma, WY Ding, M Bowden, GT Dong, ZG AF Huang, CS Ma, WY Ding, M Bowden, GT Dong, ZG TI Direct evidence for an important role of sphingomyelinase in ultraviolet-induced activation of c-Jun N-terminal kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE; SIGNAL-TRANSDUCTION; INDUCED APOPTOSIS; ZETA-ISOFORM; CERAMIDE; STRESS; AP-1; ACID; PHOSPHORYLATION; TRANSFORMATION AB Sphingomyelinase (SMase) and its product ceramide have recently attracted a great deal of attention because of their possible role in the signal transduction pathway. However, the role of sphingomyelinase in W-induced c-June N-terminal kinase (JNK) activation is still unclear. Thus, we investigated this issue directly using a genetic SMase-deficient (2 similar to 3% residual acid SMase activity) lymphoblast cell line, MS1418. The results showed that while UV irradiation markedly induces JNK activation in a normal human lymphoblast cell line, JY, it induces only weak JNK activation in MS1418 cells. This difference of JNK response to UV irradiation between these two cell lines was further observed in time course and dose response studies. In contrast, 12-0-tetradecanoylphorbol-13 acetate-induced JNK activation could be observed in both JY and MS1418 cells. Furthermore, significant JNK activation can be observed in MS1418 cells by exposure of the cells to SMase or C-2-ceramide, whereas phospholipase A(2) or phospholipase C did not show significant induction of JNK activity, and C-2-dihydroceramide and sphingosine induce only much weaker JNK activation in MS1418 cells than that by C-2-ceramide. These data demonstrated that SMase plays an essential role in UV-induced JNK activation. C1 UNIV MINNESOTA,HORMEL INST,AUSTIN,MN 55912. NIOSH,NIH,MORGANTOWN,WV 26505. UNIV ARIZONA,HLTH SCI CTR,DEPT RADIAT ONCOL,TUCSON,AZ 85724. FU NCI NIH HHS [1R29CA74916-01] NR 31 TC 103 Z9 105 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 OCT 31 PY 1997 VL 272 IS 44 BP 27753 EP 27757 DI 10.1074/jbc.272.44.27753 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YD473 UT WOS:A1997YD47300044 PM 9346918 ER PT J AU Tarcsa, E Marekov, LN Andreoli, J Idler, WW Candi, E Chung, SI Steinert, PM AF Tarcsa, E Marekov, LN Andreoli, J Idler, WW Candi, E Chung, SI Steinert, PM TI The fate of trichohyalin - Sequential, post-translational modifications by peptidyl-arginine deiminase and transglutaminases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-ENVELOPE PRECURSOR; HAIR FOLLICLE; SUBSTRATE-SPECIFICITY; HUMAN EPIDERMIS; HUMAN LORICRIN; CROSS-LINKING; GUINEA-PIG; PROTEIN; EXPRESSION; CITRULLINE AB Trichohyalin (THH) is a major structural protein of the inner root sheath cells and medulla layer of the hair follicle and, to a lesser extent, of other specialized epithelia, THH is a high molecular weight insoluble alpha-helix-rich protein that forms rigid structures as a result of postsynthetic modifications by two Ca2+-dependent enzymes, transglutaminases (TGases) (protein cross-linking) and peptidyl-arginine deiminase (conversion of arginines to citrullines with loss of organized structure), The modified THH is thought to serve as a keratin intermediate filament matrix protein and/or as a constituent of the cell envelope, In this paper, we have explored in vitro the order of processing of THH to fulfill these functions, using an expressed truncated, more soluble form THH-8, THH-8 is a complete substrate for three known TGases expressed in epithelia, but the kinetic efficiency with TGase 3 is by far the greatest. Following maximal conversion of its arginines to citrullines, THH-8 is cross-linked even more efficiently by TGase 3, using most glutamines partially and all lysines, In addition, we show that insoluble aggregates of THH-8 or native pig tongue THH can be solubilized following peptidyl-arginine deiminase modification. Together, these data suggest an in vivo model in which THH located in insoluble cytoplasmic droplets is first modified by peptidyl-arginine deiminase which denatures it and makes it more soluble. This renders it available for efficient cross-linking by TGase 3 to form highly crosslinked rigid structures in the cells, This temporal order of reaction is supported by the observation that THH is expressed in hair follicle cells before the TGase 3 enzyme. C1 NIAMS,SKIN BIOL LAB,NIH,BETHESDA,MD 20892. KOREA GREEN CROSS CORP,KYUNGGI GI DO 449900,SOUTH KOREA. NR 50 TC 104 Z9 106 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 31 PY 1997 VL 272 IS 44 BP 27893 EP 27901 DI 10.1074/jbc.272.44.27893 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YD473 UT WOS:A1997YD47300063 PM 9346937 ER PT J AU Scott, DA Docampo, R Dvorak, JA Shi, SL Leapman, RD AF Scott, DA Docampo, R Dvorak, JA Shi, SL Leapman, RD TI In situ compositional analysis of acidocalcisomes in Trypanosoma cruzi SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ELECTRON-PROBE MICROANALYSIS; ELEMENTAL COMPOSITION; CYSTEINE PROTEINASE; LYSOSOMAL COMPARTMENT; CRITHIDIA-FASCICULATA; AFRICAN TRYPANOSOMES; GRANULES INSITU; CA-2+ TRANSPORT; CALCIUM STORES; CA2+ RELEASE AB We measured the elemental content of different compartments in Trypanosoma cruzi epimastigotes using quick freezing, ultracryomicrotomy, and electron probe microanalysis. Vacuoles identified by high electron density contained (in units of mmol/kg dry weight +/- S.E.) large amounts of phosphorus (1390 +/- 13), magnesium (646 +/- 19), calcium (171 +/- 5), sodium (161 +/- 18), and zinc (148 +/- 6). No other compartment had appreciable calcium or zinc content. Iron (128 +/- 16 mmol/kg) was detected only in vacuoles distinct from the electron-dense vacuoles and other organelles. Incubation of cells for 70 min in culture medium in the presence of ionomycin plus nigericin led to a very significant 3- or 2-fold increase in potassium in the electron-dense vacuoles and the iron-rich vacuoles, respectively, with no significant change in the other elements investigated, This indicated the acidic nature of the vacuoles and demonstrated that the electron-dense vacuoles correspond to what were described previously as acidocalcisomes, i.e. acidic compartments rich in Ca2+. The acidocalcisomes were investigated by separation of epimastigote fractions on Percoll gradients in combination with Triton WR-1339 treatment. This detergent caused a rapid vacuolation; these vacuoles were shown by electron microscopy to be largely transparent, with a diffuse matrix. Percoll gradient fractionation demonstrated decreases in the density of various organelle markers in detergent-treated cells compared with controls. Large decreases in the density of the acidocalcisome and the mitochondrion were seen, as well as smaller decreases in the density of the other markers. Conventional electron microscopy of epimastigotes loaded with gold-labeled transferrin indicated that the endosomal system was separate from vacuoles that probably corresponded to the calcium-containing organelles detected by electron probe microanalysis. The combined results provide evidence that acidocalcisomes are organelles different from lysosomes or other organelles previously described in these parasites. C1 UNIV ILLINOIS,COLL VET MED,DEPT VET PATHOBIOL,MOL PARASITOL LAB,URBANA,IL 61802. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-23259] NR 71 TC 76 Z9 78 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 OCT 31 PY 1997 VL 272 IS 44 BP 28020 EP 28029 DI 10.1074/jbc.272.44.28020 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YD473 UT WOS:A1997YD47300080 PM 9346954 ER PT J AU Carr, JF Hinshaw, JE AF Carr, JF Hinshaw, JE TI Dynamin assembles into spirals under physiological salt conditions upon the addition of GDP and gamma-phosphate analogues SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COATED VESICLE FORMATION; GTP-BINDING PROTEINS; MECHANOCHEMICAL ENZYME; NERVE-TERMINALS; SH3 DOMAINS; MICROTUBULES; ENDOCYTOSIS; DROSOPHILA; MECHANISM; MUTANT AB Dynamin is a 100-kDa GTPase that is believed to be involved in the constriction of clathrin-coated pits and the fission of clathrin-coated vesicles during receptor-mediated endocytosis and during membrane retrieval in nerve termini. It has been shown that purified dynamin incubated under low salt conditions forms rings and spirals that, in dimension and appearance, resemble the dense material occasionally observed at the necks of coated pits. In this report we show that purified dynamin forms spirals under physiological salt conditions when incubated with GDP and gamma-phosphate analogues (beryllium and aluminum fluoride) or when dialyzed into guanosine 5'-3-O-(thio)triphosphate. Moreover, spirals still form when dynamin is proteolyzed to either a predominant similar to 90-kDa species, lacking the C terminus, or to two smaller fragments, a similar to 55-kDa species originating from the N-terminal half of the protein and a similar to 30-kDa species lacking both the N and C termini. This work indicates that the addition of GDP and gamma-phosphate analogues arrests dynamin in a GTP or transition state that markedly stabilizes the spiral conformation under physiological ionic strength conditions and thereby suggests that dynamin in the absence of a receptor is capable of assembly into spirals at the necks of coated pits prior to vesicle fission. RP Carr, JF (reprint author), NIDDK,LAB CELL BIOCHEM & BIOL,NIH,BETHESDA,MD 20892, USA. NR 41 TC 80 Z9 81 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 OCT 31 PY 1997 VL 272 IS 44 BP 28030 EP 28035 DI 10.1074/jbc.272.44.28030 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YD473 UT WOS:A1997YD47300081 PM 9346955 ER PT J AU Watanabe, H Cheung, SC Itano, N Kimata, K Yamada, Y AF Watanabe, H Cheung, SC Itano, N Kimata, K Yamada, Y TI Identification of hyaluronan-binding domains of aggrecan SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHONDROITIN SULFATE PROTEOGLYCAN; PIG LARYNGEAL CARTILAGE; LINK PROTEIN; EXTRACELLULAR-MATRIX; KERATAN SULFATE; BIOTINYLATED HYALURONAN; MOLECULAR-CLONING; BOVINE CARTILAGE; ACID; RECEPTOR AB Aggrecan, a large cartilage proteoglycan, interacts with hyaluronan (HA), to form aggregates which function to resist compression in joints. The N-terminal region of aggrecan contains two structurally related globular domains, G(1) and G(2) separated by IGD domain. The G(1) domain consists of three subdomains, A, B, and B', structural features characteristic to many other HA-binding proteoglycans. Here, we studied the interaction of aggrecan domains with HA using recombinant proteins expressed in 293 cells, an embryonal kidney cell line. Deglycosylation of the recombinant aggrecan fragment reduced the HA binding activity. We found that both the B and B' subdomains were required for HA binding and that a single module of A, B, or B' was unable to bind HA. The A subdomain increased the HA binding activity of the B-B' region. The G(2) domain had no HA binding activity confirming previous reports. Studies of HA-binding properties using a BIAcore(TM) biosensor system revealed that the K-D of recombinant aggrecan fragment (AgW) consisting of G(1), IGD, and G(2) was 0.226 mu M, whereas the K-D of another HA-binding protein, native bovine link protein, is 0.089 mu M. In contrast, Ag-Mut11 which lacked subdomain A showed little HA binding activity. AgMut12 consisting of only B-B' had a 3.4-fold lower affinity and AgMut13 containing A-B-B' was 1.5-fold lower than AgW. These results suggest that carbohydrates are essential for high level aggrecan binding to HA and that the A subdomain of aggrecan functions in a cooperative manner with subdomains B and B'. C1 NIDR,CRANIOFACIAL DEV BIOL & REGENERAT BRANCH,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,LAB HEMOSTASIS,ROCKVILLE,MD 20852. AICHI MED UNIV,INST MOL SCI MED,NAGAKUTE,AICHI 48011,JAPAN. NR 46 TC 89 Z9 90 U1 2 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 OCT 31 PY 1997 VL 272 IS 44 BP 28057 EP 28065 DI 10.1074/jbc.272.44.28057 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YD473 UT WOS:A1997YD47300085 PM 9346959 ER PT J AU Kim, MG CameriniOtero, RD AF Kim, MG CameriniOtero, RD TI An alteration in the structure of the minor groove of duplex DNA induced by the formation of an intermolecular d(GA)(n):d(GA)(n)center dot d(TC)(n) triplex SO MOLECULES AND CELLS LA English DT Article ID SEQUENCE-SPECIFIC RECOGNITION; HELIX FORMATION; HOMOLOGOUS RECOMBINATION; MAJOR GROOVE; HUMAN-CELLS; BINDING; RNA; INTERMEDIATE; STABILITY; PROTEINS AB A simple homopolymeric purine:purine pyrimidine, d(GA)(n):d(GA)(n) . d(TC)(n), triplex DNA was generated in the presence of magnesium ion at neutral pH. Hydrogen bonding of the N7 positions of guanines and adenines was investigated by 7-deaza base substitutions and protection from chemical modification by dimethyl sulfate (DMS). Chemical modification of this tripler with DMS revealed an unexpected tripler specific hypermodification in the N3 positions of the adenines in addition to the protection in the N7 positions of the guanines. The significance of this increase in the chemical accessibility of the N3 positions of adenines in the minor groove and possible relevance of dehydration to the mechanism of triplex formation and stability is discussed. C1 NIDDK,GENET & BIOCHEM BRANCH,NIH,BETHESDA,MD 20892. NR 42 TC 2 Z9 2 U1 0 U2 0 PU KOREAN SOC MOLECULAR BIOLOGY PI SEOUL PA KOREA SCI TECHNOLOGY CENTER, ROOM 815, 635-4 YEOGSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1016-8478 J9 MOL CELLS JI Mol. Cells PD OCT 31 PY 1997 VL 7 IS 5 BP 641 EP 647 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YD558 UT WOS:A1997YD55800012 PM 9387152 ER PT J AU Haseman, JK Hailey, JR AF Haseman, JK Hailey, JR TI An update of the National Toxicology Program database on nasal carcinogens SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE nasal cavity; rodent carcinogenity; nasal tumor; National Toxicology Program ID CANCER; RODENTS AB Nearly 500 long-term rodent carcinogenicity studies carried out by the National Cancer Institute and the National Toxicology Program were examined, and 12 chemicals were identified that produced nasal tumors: allyl glycidol ether, p-cresidine, 1,2-dibromo-3-chloropropane, 1,2-dibromoethane, 2,3-dibromo-1-propanol, dimethylvinyl chloride, 1,4-dioxane, 1,2-epoxybutane, iodinated glycerol, procarbazine, propylene oxide, and 2,6-xylidine. All 12 of these chemicals produced nasal tumors in rats, and 5 also produced nasal tumors in mice. Most of the nasal carcinogens (1) produced tumor increases in both sexes, (2) produced tumors at other sites as well, (3) had significantly reduced survival at doses that were carcinogenic, and (4) were genotoxic. Only 5 of the 12 nasal carcinogens were administered by inhalation. A variety of different types of nasal cavity tumors were produced, and specific tumor rates are given for those chemicals causing multiple tumor types. Increased incidences of nasal neoplasms were often accompanied by suppurative/acute inflammation, epithelial/focal hyperplasia and squamous metaplasia. However, high incidences of these nonneoplastic nasal lesions were also frequently seen in inhalation studies showing no evidence of nasal carcinogenicity, suggesting that in general nasal carcinogenesis is not associated with the magnitude of chronic toxicity observed at this site. (C) 1997 Elsevier Science B.V. C1 NIEHS,PATHOL BRANCH,RES TRIANGLE PK,NC 27709. RP Haseman, JK (reprint author), NIEHS,STAT & BIOMATH BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 17 TC 32 Z9 32 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD OCT 31 PY 1997 VL 380 IS 1-2 BP 3 EP 11 DI 10.1016/S0027-5107(97)00121-8 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA YE984 UT WOS:A1997YE98400002 PM 9385384 ER PT J AU Jacobsen, LK Hamburger, SD Van Horn, JD Vaituzis, AC McKenna, K Frazier, JA Gordon, CT Lenane, MC Rapoport, JL Zametkin, AJ AF Jacobsen, LK Hamburger, SD Van Horn, JD Vaituzis, AC McKenna, K Frazier, JA Gordon, CT Lenane, MC Rapoport, JL Zametkin, AJ TI Cerebral glucose metabolism in childhood onset schizophrenia SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE neurodevelopment; hypofrontality; cerebellum ID POSITRON-EMISSION TOMOGRAPHY; BLOOD-FLOW; COMPUTED-TOMOGRAPHY; HUMAN BRAIN; DISORDER; ATTENTION; HYPOFRONTALITY; HYPERACTIVITY; NEUROLEPTICS; GRADIENTS AB Decreased frontal cortical glucose metabolism has been demonstrated in adult schizophrenics both at rest and while engaging in tasks that normally increase frontal metabolism, such as the Continuous Performance Test (CPT). The authors tested the hypothesis that adolescents with childhood onset schizophrenia would also demonstrate hypofrontality while performing the CPT. Cerebral glucose metabolism was examined in 16 adolescents (mean age 14.1 +/- 1.7) with onset of schizophrenia by age 12 (mean age at onset 9.9 +/- 1.8) and 26 healthy adolescents selected to be similar in age, sex and handedness using positron emission tomography and F-18-fluorodeoxyglucose. Patients with childhood onset schizophrenia made fewer correct and more incorrect identifications on the CPT. Region of interest analysis revealed no significant group differences in global cerebral glucose metabolism, but increased metabolic rate in supramarginal gyrus (F = 6.74, P < 0.05) and inferior frontal gyrus/insula (F = 7.09, P < 0.05) and decreased metabolic rate in middle frontal gyrus (F = 6.72, P<0.05) and superior frontal gyrus (t=2.04, P<0.05) in schizophrenics. Comparison of effect sizes with an identically designed study of adult schizophrenics did not indicate more severe hypofrontality in childhood onset schizophrenia. Pixel-based analyses indicated a more complex pattern of group differences in cerebral metabolism with bilaterally increased cerebellar metabolic rate in childhood onset schizophrenics. These findings suggest that childhood onset schizophrenia may be associated with a similar, but not more severe, degree of hypofrontality relative to that seen in adult onset schizophrenia. (C) 1997 Elsevier Science Ireland Ltd. C1 Yale Univ, Sch Med, Dept Psychiat, VA Connecticut Hlth Care Syst 116A, W Haven, CT 06516 USA. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, Washington, DC 20032 USA. Northwestern Univ, Sch Med, Chicago, IL 60614 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NIMH, Off Clin Director, Bethesda, MD 20892 USA. RP Jacobsen, LK (reprint author), Yale Univ, Sch Med, Dept Psychiat, VA Connecticut Hlth Care Syst 116A, 950 Campbell Ave, W Haven, CT 06516 USA. NR 49 TC 23 Z9 23 U1 2 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD OCT 31 PY 1997 VL 75 IS 3 BP 131 EP 144 DI 10.1016/S0925-4927(97)00050-4 PG 14 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA YM923 UT WOS:000071115400001 PM 9437771 ER PT J AU Chittum, HS Hill, KE Carlson, BA Lee, BJ Burk, RF Hatfield, DL AF Chittum, HS Hill, KE Carlson, BA Lee, BJ Burk, RF Hatfield, DL TI Replenishment of selenium deficient rats with selenium results in redistribution of the selenocysteine tRNA population in a tissue specific manner SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE selenium; selenium deficiency; selenium replenishment; selenocysteine; seryl-tRNA; tRNA ID TRANSFER RNASEC; MAMMALIAN-CELLS; TRANSFER-RNAS; METHYLATION; CODON; UGA AB We reported previously that the selenium status of rats influences both the steady-state levels and distributions of two selenocysteine tRNA isoacceptors and that these isoacceptors differ by a single methyl group attached to the ribosyl moiety at position 34. In this study, we demonstrate that repletion of selenium-deficient rats results in a gradual, tissue-dependent shift in the distribution of these isoacceptors. Rats fed a selenium-deficient diet possess a greater abundance of the species unmethylated on the ribosyl moiety at position 34 compared to the form methylated at this position. A redistribution of the Sec-tRNA isoacceptors occurred in tissues of selenium-supplemented rats whereby the unmethylated form gradually shifted toward the methylated form. This was true in each of four tissues examined, muscle, kidney, liver and heart, although the rate of redistribution was tissue-specific. Muscle manifested a predominance of two minor serine isoacceptors under conditions of extreme selenium-deficiency which also appeared to respond to selenium. Ribosomal binding studies revealed that one of the two additional isoacceptors decodes the serine codeword, AGU, and the second decodes the serine codeword, UCU. Interestingly, muscle and heart were the slower tissues to return to a 'selenium adequate' tRNA distribution pattern. (C) 1997 Elsevier Science B.V. C1 NCI,MOL BIOL SELENIUM SECT,BASIC RES LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. VANDERBILT UNIV,SCH MED,DEPT MED,DIV GASTROENTEROL,NASHVILLE,TN 37232. VANDERBILT UNIV,SCH MED,CLIN NUTR RES UNIT,NASHVILLE,TN 37232. SEOUL NATL UNIV,INST MOL BIOL & GENET,GENET MOL LAB,SEOUL 151742,SOUTH KOREA. FU NIEHS NIH HHS [ES02497] NR 20 TC 38 Z9 38 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD OCT 30 PY 1997 VL 1359 IS 1 BP 25 EP 34 DI 10.1016/S0167-4889(97)00092-X PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YG699 UT WOS:A1997YG69900003 PM 9398082 ER PT J AU Weissman, D Rabin, RL Arthos, J Rubbert, A Dybul, M Swofford, R Venkatesan, S Farber, JM Fauci, AS AF Weissman, D Rabin, RL Arthos, J Rubbert, A Dybul, M Swofford, R Venkatesan, S Farber, JM Fauci, AS TI Macrophage-tropic HIV and SIV envelope proteins induce a signal through the CCR5 chemokine receptor SO NATURE LA English DT Article ID INFECTION; DISEASE; VACCINE; ENTRY AB Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) enter target cells by forming a complex between the viral envelope protein and two cell-surface membrane receptors: CD4 and a 7-span transmembrane chemokine receptor (reviewed in refs 1-3). Isolates of HIV that differ in cellular tropism use different subsets of chemokine receptors as entry cofactors: macrophage-tropic HIVs primarily use CCR5, whereas T-cell-tropic and dual-tropic isolates use CXCR4 (refs 1-3) receptors. HIV-mediated signal transduction through CCR5 is not required for efficient fusion and entry of HIV in vitro(4,5). Here we show that recombinant envelope proteins from macrophage-tropic HIV and SIV induce a signal through CCR5 on CD4(+) T cells and that envelope-mediated signal transduction through CCR5 induces chemotaxis of T cells. This chemotactic response may contribute to the pathogenesis of HIV in vivo by chemo-attracting activated CD4(+) cells to sites of viral replication(1,2). HIV-mediated signalling through CCR5 may also enhance viral replication in vivo by increasing the activation state of target cells. Alternatively, envelope-mediated CCR5 signal transduction may influence viral-associated cytopathicity or apoptosis. C1 NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,FLO CYTOMETRY UNIT,NIH,BETHESDA,MD 20892. NIAID,MOL MICROBIOL LAB,NIH,BETHESDA,MD 20892. NR 18 TC 279 Z9 284 U1 0 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD OCT 30 PY 1997 VL 389 IS 6654 BP 981 EP 985 DI 10.1038/40173 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YD299 UT WOS:A1997YD29900059 PM 9353123 ER PT J AU Magrath, I AF Magrath, I TI Limiting therapy for limited childhood non-Hodgin's lymphoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID FRANKFURT-MUNSTER GROUP; NON-HODGKINS-LYMPHOMA RP Magrath, I (reprint author), NIH,BETHESDA,MD 20892, USA. NR 11 TC 11 Z9 11 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 OCT 30 PY 1997 VL 337 IS 18 BP 1304 EP 1306 DI 10.1056/NEJM199710303371810 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA YC920 UT WOS:A1997YC92000010 PM 9345082 ER PT J AU Sternberg, EM AF Sternberg, EM TI Intimidation of researchers by special-interest groups SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID EOSINOPHILIA-MYALGIA-SYNDROME; TRYPTOPHAN; 1,1'-ETHYLIDENEBIS(L-TRYPTOPHAN) RP Sternberg, EM (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 6 TC 0 Z9 0 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 OCT 30 PY 1997 VL 337 IS 18 BP 1316 EP 1316 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA YC920 UT WOS:A1997YC92000020 PM 9380084 ER PT J AU Clark, J Lu, YJ Sidhar, SK Parker, C Gill, S Smedley, D Hamoudi, R Linehan, WM Shipley, J Cooper, CS AF Clark, J Lu, YJ Sidhar, SK Parker, C Gill, S Smedley, D Hamoudi, R Linehan, WM Shipley, J Cooper, CS TI Fusion of splicing factor genes PSF and NonO (p54(nrb)) to the TFE3 gene in papillary renal cell carcinoma SO ONCOGENE LA English DT Article DE renal cell carcinoma; PSF splicing factor; NonO (p54(nrb)) splicing factor; chromosome translocations; TFE3 transcription factor ID TUMOR-SUPPRESSOR GENE; ALVEOLAR RHABDOMYOSARCOMA; TRANSLOCATION X-1; BINDING PROTEIN; TRANSCRIPTION; CYTOGENETICS; RNA; BREAKPOINT; SARCOMA; ADENOCARCINOMA AB We demonstrate that the cytogenetically defined translocation t(X;1)(p11.2;p34) observed in papillary renal cell carcinomas results in the fusion of the splicing factor gene PSF located at 1p34 to the TFE3 helix-loop-helix transcription factor gene at Xp11.2. In addition we define an X chromosome inversion inv(X)(p11.2;q12) that results in the fusion of the NonO (p54(nrb)) gene to TFE3. NonO (p54(nrb)), the human homologue of the Drosophila gene NonA(diss) which controls the male courtship song, is closely related to PSF and also believed to be involved in RNA splicing. In each case the rearrangement results in the fusion of almost the entire splicing factor protein to the TFE3 DIVA-binding domain. These observations suggest the possibility of intriguing links between the processes of RNA splicing, DNA transcription and oncogenesis. C1 INST CANC RES,HADDOW LABS,SECT CELL BIOL & EXPT PATHOL,SUTTON SM2 5NG,SURREY,ENGLAND. INST CANC RES,HADDOW LABS,CANC GENE CLONING LAB,SUTTON SM2 5NG,SURREY,ENGLAND. NCI,UROL ONCOL SECT,BETHESDA,MD 20892. RP Clark, J (reprint author), INST CANC RES,HADDOW LABS,SECT MOL CARCINOGENESIS,SUTTON SM2 5NG,SURREY,ENGLAND. NR 37 TC 177 Z9 187 U1 0 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 30 PY 1997 VL 15 IS 18 BP 2233 EP 2239 DI 10.1038/sj.onc.1201394 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA YD019 UT WOS:A1997YD01900012 PM 9393982 ER PT J AU Lebowitz, BD AF Lebowitz, BD TI The future of clinical research in mental disorders of late life SO SCHIZOPHRENIA RESEARCH LA English DT Article DE clinical research; geriatric psychiatry; late-life mental illness ID ALZHEIMERS-DISEASE; DEPRESSION; WOMEN; CARE; COMMUNITY; TRIAL; RISK AB After years of neglect, clinical research into late-life mental disorders is receiving the attention it deserves. Geriatric psychiatry is a growing field and the insights gained from research in this area have improved the diagnosis and treatment of mental illness in older persons. The challenge for the future is to continue to maintain a leadership role in mental health while working within the constraints of the managed care system in the United States. (C) 1997 Elsevier Science B.V. RP Lebowitz, BD (reprint author), NIMH,MENTAL DISORDERS AGING RES BRANCH,5600 FISHERS LANE,ROOM 18-101,ROCKVILLE,MD 20857, USA. NR 41 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT 30 PY 1997 VL 27 IS 2-3 BP 261 EP 267 DI 10.1016/S0920-9964(97)00064-9 PG 7 WC Psychiatry SC Psychiatry GA YH234 UT WOS:A1997YH23400016 PM 9416655 ER PT J AU Zambito, AM Wolff, J AF Zambito, AM Wolff, J TI Palmitoylation of tubulin SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE tubulin; palmitoylation; PC12; EGF ID PC12 PHEOCHROMOCYTOMA CELLS; NERVE GROWTH-FACTOR; FATTY ACYLATION; PROTEIN; MEMBRANE; LIPIDATION; BRAIN AB Tubulin is a very water soluble protein, yet a significant portion is firmly associated with cell membranes, Because recent work has shown that palmitoylation is a dynamic process that can alter the targeting of proteins to membranes, we tested whether or not tubulin could be palmitoylated to account for its membrane location, Tubulin acylation was measured by in corporation of [H-3]palmitate into PC12 cells in culture. We found palmitoylated tubulin in both cell pellet and cytosol, with a higher concentration in the former. EGF-stmulated PC12 cells incorporated the same amount of palmitate per unit protein but the proportion in the membrane fraction was enhanced. More palmitate of the pellet was found in alpha than beta tubulin; EGF stimulation primarily increased palmitate in beta tubulin. In addition we found that palmitic acid was present both as thioesters and as oxyesters, We suggest that, palmitoylation may contribute to the membrane localization of tubulin and can be regulated by growth factors. (C) 1997 Academic Press. C1 NIDDKD,BIOCHEM PHARMACOL LAB,NIH,BETHESDA,MD 20892. NR 19 TC 24 Z9 24 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 29 PY 1997 VL 239 IS 3 BP 650 EP 654 DI 10.1006/bbrc.1997.7525 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YG931 UT WOS:A1997YG93100003 PM 9367822 ER PT J AU Schulte, TW An, WG Neckers, LM AF Schulte, TW An, WG Neckers, LM TI Geldanamycin-induced destabilization of Raf-1 involves the proteasome SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ACTIVATED PROTEIN-KINASE; ROUS-SARCOMA VIRUS; RAT-KIDNEY CELLS; SIGNAL-TRANSDUCTION; TYROSINE KINASE; HERBIMYCIN-A; MAP KINASE; IN-VIVO; PROGESTERONE-RECEPTOR; GROWTH-FACTOR AB The Raf-1-MEK-MAPK pathway plays an important role in transducing extracellular growth factor signaling into altered nuclear transcription factor function, The benzoquinone ansamycin Geldanamycin (GA) specifically binds to the heat shock protein HSP90 and alters its complex with Raf-1. This leads to a decrease in Raf-1 levels and to disruption of the Raf-1-MEK-MAPK signaling pathway, The enhanced degradation of Raf-1 protein was prevented by inhibitors of the proteasome, while inhibition of lysosomal or other proteases was ineffective, Raf-1 that was protected from GA-induced degradation was of higher molecular weight and showed a laddering pattern consistent with its polyubiquitination. Unlike Raf-1 in untreated cells, the protein was insoluble in Triton X100- or NP40-based buffers, Signaling through this pathway was inhibited by GA, concomitant with loss of Raf-1 protein, but was restored if Raf-1 was protected from GA-induced degradation by proteasome inhibitors. (C) 1997 Academic Press. RP Schulte, TW (reprint author), NCI,MED BRANCH,NIH,BLDG 10,ROOM 13N240,10 CTR DR MSC 1928,BETHESDA,MD 20892, USA. NR 55 TC 149 Z9 155 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 OCT 29 PY 1997 VL 239 IS 3 BP 655 EP 659 DI 10.1006/bbrc.1997.7527 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YG931 UT WOS:A1997YG93100004 PM 9367823 ER PT J AU Hamawy, MM Fischler, C Zhang, J Siraganian, RP AF Hamawy, MM Fischler, C Zhang, J Siraganian, RP TI Fc epsilon RI aggregation induces tyrosine phosphorylation of a novel 72 kDa protein downstream of syk SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; SIGNAL-TRANSDUCTION; RECEPTOR AGGREGATION; HISTAMINE-RELEASE; KINASE P72(SYK); RBL-2H3 CELLS; MAST-CELLS; IGE; COMPONENT; DEGRANULATION AB Tyrosine phosphorylation of proteins is critical for the Fc epsilon RI-induced signal transduction that leads to the release of inflammatory mediators from mast cells, Here we report the isolation of a monoclonal antibody, mAb BD2, to a 72 hDa protein that becomes rapidly tyrosine phosphorylated after Fc epsilon RI aggregation. By immunoprecipitation, immunoblotting and/or protease digestion this 72 kDa protein was different from the previously identified 68-76 kDa tyrosine phosphorylated proteins Btk, paxillin, SLP-76 or Syk, The phosphorylation of this 72 kDa protein was detectable within 15 sec after receptor aggregation and was independent of Ca2+ influx or the activation of protein kinase C. By in vitro kinase reaction, the 12 kDa protein did not autophosphorylate, which suggests that it is not a kinase, but is associated with a 140 kDa protein that was strongly phosphorylated. Studies in Syk deficient and Syk transfected variants of the RBL-2H3 cells demonstrated that the tyrosine phosphorylation of this 12 kDa protein was downstream of Syk, These data indicate that the 72 kDa protein precipitated by mAb BD2 Is a novel phosphoprotein involved in Fc epsilon RI signaling. (C) 1997 Academic Press. RP Hamawy, MM (reprint author), NIDR,OIIB,RECEPTORS & SIGNAL TRANSDUCT SECT,NIH,BETHESDA,MD 20892, USA. NR 22 TC 8 Z9 9 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 OCT 29 PY 1997 VL 239 IS 3 BP 670 EP 675 DI 10.1006/bbrc.1997.7532 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YG931 UT WOS:A1997YG93100007 PM 9367826 ER PT J AU Mori, T Shoemaker, RH McMahon, JB Gulakowski, RJ Gustafson, KR Boyd, MR AF Mori, T Shoemaker, RH McMahon, JB Gulakowski, RJ Gustafson, KR Boyd, MR TI Construction and enhanced cytotoxicity of a [Cyanovirin-N]-[Pseudomonas exotoxin] conjugate against human immunodeficiency virus-infected cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID RECOMBINANT SOLUBLE CD4; HTLV-III/LAV ENVELOPE; PSEUDOMONAS EXOTOXIN; PHASE-I; HIV; TYPE-1; AIDS; NEUTRALIZATION; GLYCOPROTEIN; RECEPTORS AB Cyanovirin-N (CV-N) is a novel 11-kDa anti-HIV(human immunodeficiency virus) protein that binds with high affinity to the viral envelope glycoprotein gp120, in contrast to soluble CD4 and most known neutralizing antibodies that bind gp120, CV-N exerts potent anti-viral activity against primary clinical HN isolates as well as laboratory-adapted strains of HIV. Here we describe the recombinant production, purification, and characterization of a chimeric toxin molecule, FLAG-CV-N-PE38, that contains CV-N as a gp120-targeting moiety linked to the translocation and cytotoxic domains of Pseudomonas exotoxin A. FLAG-CV-N-PE38 showed enhanced cytotoxicity to HIV-infected, gp120-expressing H9 cells compared to uninfected H9 cells. Competition experiments with free CV-N provided further support that the enhanced FLAG-CV-N-PE38-induced cytotoxicity was due to interactions of the CV-N moiety with cell surface gp120. This study establishes the feasibility of use of CV-N as a gp120-targeting sequence for construction and experimental therapeutic investigations of unique new chimeric toxins designed to selectively destroy HIV-infected host cells. (C) 1997 Academic Press. C1 NCI,LAB DRUG DISCOVERY RES & DEV,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT DIAG & CTR,FREDERICK,MD 21702. NR 34 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 29 PY 1997 VL 239 IS 3 BP 884 EP 888 DI 10.1006/bbrc.1997.7505 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YG931 UT WOS:A1997YG93100045 PM 9367864 ER PT J AU Mishkin, M Suzuki, WA Gadian, DG VarghaKhadem, F AF Mishkin, M Suzuki, WA Gadian, DG VarghaKhadem, F TI Hierarchical organization of cognitive memory SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT Royal-Society Discussion Meeting on What are the Parietal and Hippocampal Contributions to Spatial Cognition CY MAR 19-29, 1997 CL LONDON, ENGLAND SP Royal Soc ID ENTORHINAL AREA 28; PARAHIPPOCAMPAL CORTICES; HIPPOCAMPAL-FORMATION; VISUAL RECOGNITION; PERIRHINAL CORTEX; RHESUS-MONKEYS; LOBE AFFERENTS; 35 CORTICES; IMPAIRMENT; AMNESIA AB This paper addresses the question of the organization of memory processes within the medial temporal lobe. Evidence obtained in patients with late-onset amnesia resulting from medial temporal pathology has given rise to two opposing interpretations of the effects of such damage on long-term cognitive memory. One view is that cognitive memory, including memory for both facts and events, is served in a unitary manner by the hippocampus and its surrounding cortices; the other is that the basic function affected in amnesia is event memory, the memory for factual material often showing substantial preservation. Recent findings in patients with amnesia resulting from relatively selective hippocampal damage sustained early in life suggest a possible reconciliation of the two views. The new findings suggest that the hippocampus may be especially important for event as opposed to fact memory with the surrounding cortical areas contributing to both. Evidence from neuroanatomical and neurobehavioural studies in monkeys is presented in support of this proposal. C1 UCL, SCH MED, RADIOL & PHYS UNIT, INST CHILD HLTH, LONDON WC1N 1EH, ENGLAND. UCL, SCH MED, INST CHILD HLTH, COGNIT NEUROSCI UNIT, LONDON WC1N 1EH, ENGLAND. RP Mishkin, M (reprint author), NIMH, NEUROPSYCHOL LAB, BETHESDA, MD 20892 USA. RI Gadian, David/C-4961-2008; Vargha-Khadem, Faraneh/C-2558-2008 NR 54 TC 177 Z9 183 U1 0 U2 12 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 J9 PHILOS T R SOC B JI Philos. Trans. R. Soc. B-Biol. Sci. PD OCT 29 PY 1997 VL 352 IS 1360 BP 1461 EP 1467 PG 7 WC Biology SC Life Sciences & Biomedicine - Other Topics GA YE009 UT WOS:A1997YE00900008 PM 9368934 ER PT J AU Vance, JE LeBlanc, DA London, RE AF Vance, JE LeBlanc, DA London, RE TI Cleavage of the X-Pro peptide bond by pepsin is specific for the trans isomer SO BIOCHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RETROVIRAL PROTEASE; ASPARTIC PROTEASE; TYPE-1 PROTEASE; HIV-1 PROTEASE; PROLINE; SUBSTRATE; PROTEINASE; INHIBITORS; PEPSTATIN AB Fluorine nuclear magnetic resonance studies of the cleavage of peptides containing a 4-fluorophenylalanin (FPhe)-Pro bond have been performed in order to determine the conformational specificity of FPhe-Pro bond cleavage by pepsin. The peptides selected were substrates of HIV protease or of avian sarcoma virus protease, both of which have been reported to be cleaved specifically at X-Pro by pepsin as well as by the corresponding viral protease enzyme. By working at 0 degrees C, it was possible to separate kinetically cleavage and cis/trans isomerization. For the case of the protease substrate, Ser-Gln-Asn-FPhe-Pro-Ile-Val-Gln, cleavage was shown to be specific for the trans conformation. A value for the rate constant for hydrolysis of the trans peptide divided by the Michaelis constant, k(tH)/K-M(trans) = 0.3 min(-1) mM(-1) was obtained with this substrate, and the Michaelis constant appears to be considerably higher than the substrate concentration, 3.7 mM, used in the study. On a slower time scale, additional cleavages can readily be detected. For the avian leukemia virus protease substrate, Thr-Phe-Gln-Ala-FPhe-Pro-Leu-Arg-Glu-Ala, the cleavage was both slower and less specific. In addition to the primary cleavage at the FPhe-Pro site, cleavage also occurs at the Ala-FPhe bond on a somewhat slower time scale. In addition to the conformational specificity of the cleavage reaction, these results indicate that pepsin is a better model for HIV protease than for avian leukemia virus protease. C1 NIEHS,STRUCT BIOL LAB,RES TRIANGLE PK,NC 27709. NR 35 TC 12 Z9 12 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 28 PY 1997 VL 36 IS 43 BP 13232 EP 13240 DI 10.1021/bi970918b PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YD649 UT WOS:A1997YD64900012 PM 9341212 ER PT J AU Kane, DJ Fendler, K Grell, E Bamberg, E Taniguchi, K Froehlich, JP Clarke, RJ AF Kane, DJ Fendler, K Grell, E Bamberg, E Taniguchi, K Froehlich, JP Clarke, RJ TI Stopped-flow kinetic investigations of conformational changes of pig kidney Na+,K+-ATPase SO BIOCHEMISTRY LA English DT Article ID FLUORESCEIN 5'-ISOTHIOCYANATE MODIFICATION; YEAST GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; NICOTINAMIDE-ADENINE DINUCLEOTIDE; CO-OPERATIVE BINDING; (NA+ + K+)-ATPASE; ADENOSINE-TRIPHOSPHATASE; CHARGE TRANSLOCATION; NA+/K+-ATPASE; SODIUM-PUMP; NA,K PUMP AB The kinetics of Na+-dependent partial reactions of the Na+,K+-ATPase were investigated via the stopped-flow technique using the fluorescent labels RH421 and BLPM. After the enzyme is mixed with MgATP, both labels give almost identical kinetic responses. Under the chosen experimental conditions two exponential time functions are necessary to fit the data. The dominant fast phase, 1/tau(1) approximate to 180 s(-1) (saturating [ATP] and [Na+], pH 7.4 and 24 degrees C), is attributed to phosphorylation of the enzyme and a subsequent conformational change (E(1)ATP(Na+)(3) --> E2P(Na+)(3) + ADP). The rate of the phosphorylation reaction measured by the acid quenched-flow technique was 190 s(-1) at 100 mu M ATP, suggesting that phosphorylation controls the kinetics of the RH421 signal and that the conformational change is very fast (greater than or equal to 600 s(-1)). The rate of the RH421 signal was optimal at pH 7.5. The Na+ concentration dependence of 1/tau(1) showed half-saturation at a Na+ concentration of 8-10 mM with positive cooperativity involved in the occupation of the Na+ binding sites. The apparent dissociation constant of the high affinity ATP binding site determined from the ATP concentration dependence of 1/tau(1) was 7.0 (+/-0.6) mu M, while the apparent K-d for the low affinity site and the rate constant for the E-2 to E-1 conformational change evaluated in the absence of Mg2+ were 143 (+/-17) mu M and less than or equal to 28 s(-1) At RH421 concentrations in the micromolar range, a decrease in the value of 1/tau(1) is observed. On the basis of rapid quenched-flow measurements, this inhibition can be attributed to a reaction step subsequent to phosphorylation. This accounts for previously observed kinetic discrepancies between RH421 and BIPM. C1 MAX PLANCK INST BIOPHYS, DEPT BIOPHYS CHEM, D-60596 FRANKFURT, GERMANY. HOKKAIDO UNIV, GRAD SCH SCI, DEPT PHARMACOL, DIV CHEM, SAPPORO, HOKKAIDO 060, JAPAN. NIA, CARDIOVASC SCI LAB, NIH, BALTIMORE, MD 21224 USA. RI Clarke, Ronald/L-5259-2016 OI Clarke, Ronald/0000-0002-0950-8017 NR 81 TC 62 Z9 62 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 28 PY 1997 VL 36 IS 43 BP 13406 EP 13420 DI 10.1021/bi970598w PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YD649 UT WOS:A1997YD64900034 PM 9341234 ER PT J AU Wang, Z Jiang, H Yang, ZQ Chacko, S AF Wang, Z Jiang, H Yang, ZQ Chacko, S TI Both N-terminal myosin-binding and C-terminal actin-binding sites on smooth muscle caldesmon are required for caldesmon-mediated inhibition of actin filament velocity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HEAVY-MEROMYOSIN; CHICKEN GIZZARD; ATPASE ACTIVITY; CALMODULIN-BINDING; F-ACTIN; FUNCTIONAL DOMAINS; FORCE MAINTENANCE; ACTIVATED ATPASE; FULL-LENGTH; AMINO-ACIDS AB It has been suggested that the tethering caused by binding of the N-terminal region of smooth muscle caldesmon (CaD) to myosin and its C-terminal region to actin contributes to the inhibition of actin-filament movement over myosin heads in an in vitro motility assay, However, direct evidence for this assumption has been lacking, In this study, analysis of baculovirus-generated N-terminal and C-terminal deletion mutants of chicken-gizzard CaD revealed that the major myosin-binding site on the CaD molecule resides in a 30-amino acid stretch between residues 24 and 53, based on the very low level of binding of CaD Delta 24-53 lacking the residues 24-53 to myosin compared with the level of binding of CaD Delta 54-85 missing the adjacent residues 54-85 or of the full-length CaD. As expected, deletion of the region between residues 24 and 53 or between residues 54 and 85 had no effect on either actin-binding or inhibition of actomyosin ATPase activity, Deletion of residues 24-53 nearly abolished the ability of CaD to inhibit actin filament velocity in the in vitro motility experiments, whereas CaD Delta 54-85 strongly inhibited actin filament velocity in a manner similar to that of full-length CaD, Moreover, CaD1-597, which lacks the major actin-binding site(s), did not inhibit actin-filament velocity despite the presence of the major myosin-binding site, These data provide direct evidence for the inhibition of actin filament velocity in the in vitro motility assay caused by the tethering of myosin to actin through binding of both the CaD N-terminal region to myosin and the C-terminal region to actin. C1 UNIV PENN,SCH VET MED,DEPT PATHOBIOL,PHILADELPHIA,PA 19104. UNIV PENN,DIV UROL,PHILADELPHIA,PA 19104. NHLBI,MOL CARDIOL LAB,NIH,BETHESDA,MD 20892. FU NIDDK NIH HHS [DK 39740, DK 47514] NR 64 TC 41 Z9 41 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 OCT 28 PY 1997 VL 94 IS 22 BP 11899 EP 11904 DI 10.1073/pnas.94.22.11899 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YD506 UT WOS:A1997YD50600029 PM 9342334 ER PT J AU Otterson, GA Chen, WD Coxon, AB Khleif, SN Kaye, FJ AF Otterson, GA Chen, WD Coxon, AB Khleif, SN Kaye, FJ TI Incomplete penetrance of familial retinoblastoma linked to germ-line mutations that result in partial loss of RB function SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CELL-CYCLE; GENE-PRODUCT; HEREDITARY RETINOBLASTOMA; SPONTANEOUS REGRESSION; SUSCEPTIBILITY GENE; GROWTH SUPPRESSION; AMINO-TERMINUS; LUNG-CANCER; PROTEIN; KINASE AB To study the molecular basis for the clinical phenotype of incomplete penetrance of familial retinoblastoma, we have examined the functional properties of three RB mutations identified in the germ line of five different families with low penetrance, RB mutants isolated from common adult cancers and from classic familial retinoblastoma (designated as classic RB mutations) are unstable and generally do not localize to the nucleus, do not undergo cyclin-dependent kinase (cdk)-mediated hyperphosphorylation, show absent protein ''pocket'' binding activity, and do not suppress colony growth of RB(-) cells, In contrast, two low-penetrant alleles (661W and ''deletion of codon 480'') retained the ability to localize to the nucleus, showed normal cdk-mediated hyperphosphorylation in vivo, exhibited a binding pattern to simian virus 40 large T antigen using a quantitative yeast two-hybrid assay that was intermediate between classic mutants (null) and wild-type RE, and had absent E2F1 binding in vitro, A third, low-penetrant allele, ''deletion of RB exon 4,'' showed minimal hyperphosphorylation in vivo but demonstrated detectable E2F1 binding in vitro, In addition, each low-penetrant RE mutant retained the ability to suppress colony growth of RB(-) tumor cells. These? findings suggest two categories Of mutant, low-penetrant RE alleles, Class 1 alleles correspond to promotor mutations, which are believed to result in reduced or deregulated levels of wild-type RE: protein, whereas class 2 alleles result in mutant proteins that retain partial activity, Characterization of the different subtypes of class 2 low-penetrant genes may help to define more precisely functional domains within the RE product required for tumor suppression. C1 NCI,DEPT GENET,MED BRANCH,DIV CLIN SCI,BETHESDA,MD 20889. RI kaye, frederic/E-2437-2011; CHEN, WEI-DONG/F-4521-2014 OI CHEN, WEI-DONG/0000-0003-2264-5515 NR 30 TC 66 Z9 68 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 28 PY 1997 VL 94 IS 22 BP 12036 EP 12040 DI 10.1073/pnas.94.22.12036 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YD506 UT WOS:A1997YD50600053 PM 9342358 ER PT J AU Goletz, TJ Klimpel, KR Arora, N Leppla, SH Keith, JM Berzofsky, JA AF Goletz, TJ Klimpel, KR Arora, N Leppla, SH Keith, JM Berzofsky, JA TI Targeting HIV proteins to the major histocompatibility complex class I processing pathway with a novel gp120-anthrax toxin fusion protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ANTHRACIS PROTECTIVE ANTIGEN; CYTOTOXIC LYMPHOCYTE-T; LETHAL FACTOR; DIPHTHERIA-TOXIN; MAMMALIAN-CELLS; BACILLUS-ANTHRACIS; ADENYLATE-CYCLASE; PSEUDOMONAS EXOTOXIN; ENVELOPE PROTEIN; ESCHERICHIA-COLI AB A challenge for subunit vaccines whose goal is to elicit CD8(+) cytotoxic T lymphocytes (CTLs) is to deliver the antigen to the cytosol of the living cell, where it can be processed for presentation by major histocompatibility complex (MHC) class I molecules. Several bacterial toxins have evolved to efficiently deliver catalytic protein moieties to the cytosol of eukaryotic cells. Anthrax lethal toxin consists of two distinct proteins that combine to form the active toxin, Protective antigen (PA) binds to cells and is instrumental in delivering lethal factor (LF) to the cell cytosol, To test whether the lethal factor protein could be exploited for delivery of exogenous proteins to the MHC class I processing pathway, we constructed a genetic fusion between the amino-terminal 254 aa of LF and the gp120 portion of the HIV-1 envelope protein, Cells treated with this fusion protein (LF254-gp120) in the presence of PA effectively processed gp120 and presented an epitope recognized by HIV-1 gp120 V3-specific CTL, In contrast, when cells were treated with the LF254-gp120 fusion protein and a mutant PA protein defective for translocation, the cells were not able to present the epitope and were not lysed by the specific CTL, The entry into the cytosol and dependence on the classical cytosolic MHC class I pathway were confirmed by showing that antigen presentation by PA + LF254-gp120 was blocked by the proteasome inhibitor lactacystin. These data demonstrate the ability of the LF amino-terminal fragment to deliver antigens to the MHC class I pathway and provide the basis for the development of novel T cell vaccines. C1 NIDR,ORAL INFECT & IMMUN BRANCH,NIH,BETHESDA,MD 20892. NCI,METAB BRANCH,MOL IMMUNOGENET & VACCINE RES SECT,DIV CLIN SCI,BETHESDA,MD 20892. NR 63 TC 75 Z9 78 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 OCT 28 PY 1997 VL 94 IS 22 BP 12059 EP 12064 DI 10.1073/pnas.94.22.12059 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YD506 UT WOS:A1997YD50600057 PM 9342362 ER PT J AU Malech, HL Maples, PB WhitingTheobald, N Linton, GF Sekhsaria, S Vowells, SJ Li, F Miller, JA DeCarlo, E Holland, SM Leitman, SF Carter, CS Butz, RE Read, EJ Fleisher, TA Schneiderman, RD VanEpps, DE Spratt, SK Maack, CA Rokovich, JA Cohen, LK Gallin, JI AF Malech, HL Maples, PB WhitingTheobald, N Linton, GF Sekhsaria, S Vowells, SJ Li, F Miller, JA DeCarlo, E Holland, SM Leitman, SF Carter, CS Butz, RE Read, EJ Fleisher, TA Schneiderman, RD VanEpps, DE Spratt, SK Maack, CA Rokovich, JA Cohen, LK Gallin, JI TI Prolonged production of NADPH oxidase-corrected granulocytes after gene therapy of chronic granulomatous disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PERIPHERAL-BLOOD PROGENITORS; BONE-MARROW TRANSPLANTATION; COLONY-STIMULATING FACTOR; CELLS; ENGRAFTMENT; TARGET; FORMS; MICE AB Little is known about the potential for engraftment of autologous hematopoietic stem cells in human adults not subjected to myeloablative conditioning regimens. Five adult patients with the p47(phox) deficiency form of chronic granulomatous disease received intravenous infusions of autologous CD34(+) peripheral blood stem cells (PBSCs) that had been transduced ex vivo with a recombinant retrovirus encoding normal p47(phox). Although marrow conditioning was not given, functionally corrected granulocytes were detectable in peripheral blood of all five patients. Peak correction occurred 3-6 weeks after infusion and ranged from 0.004 to 0.05% of total peripheral blood granulocytes. Corrected cells were detectable for as long as 6 months after infusion in some individuals. Thus, prolonged engraftment of autologous PBSCs and continued expression of the transduced gene can occur in adults without conditioning. This trial also piloted the use of animal protein-free medium and a blood-bank-compatible closed system of gas-permeable plastic containers for culture and transduction of the PBSCs. These features enhance the safety of PBSCs directed gene therapy. C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CLIN PATHOL,BETHESDA,MD 20892. BAXTER HEALTHCARE CORP,DIV IMMUNOTHERAPY,ROUND LAKE,IL 60073. BAXTER HEALTHCARE CORP,GENE THERAPY DIV,ROUND LAKE,IL 60073. CELL GENESYS,FOSTER CITY,CA 94404. RP Malech, HL (reprint author), NIAID,HOST DEF LAB,NIH,10 CTR DR,MSC 1886,BETHESDA,MD 20892, USA. NR 34 TC 217 Z9 220 U1 0 U2 4 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 OCT 28 PY 1997 VL 94 IS 22 BP 12133 EP 12138 DI 10.1073/pnas.94.22.12133 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YD506 UT WOS:A1997YD50600070 PM 9342375 ER PT J AU Rai, SS Wolff, J AF Rai, SS Wolff, J TI Dissociation of tubulin assembly-inhibiting and aggregation-promoting activities by a vinblastine derivative SO FEBS LETTERS LA English DT Article DE vinblastine; vinblastine-4'-anthranilate; tubulin assembly inhibition; spiral aggregate ID CALF BRAIN TUBULIN; MAYTANSINE-BINDING; MICROTUBULES; PROTEINS; SITE AB A fluorescent vinblastine analogue, vinblastine-4'-anthranilate (Antvin), that binds to the vinca site on tubulin, inhibits tubulin assembly but does not lead to spiral or other large aggregate formation at concentrations up to 1.6 mM, As judged by turbidity, 90 degrees light scattering and fluorescence anisotropy, little aggregation could be detected, This is in marked contrast to vinblastine and suggests that inhibition of assembly and aggregate formation can be dissociated from each other by suitable substitution in vinblastine. (C) 1997 Federation of European Biochemical Societies. RP Rai, SS (reprint author), NIDDK,BIOCHEM PHARMACOL LAB,NIH,BETHESDA,MD 20892, USA. NR 18 TC 4 Z9 4 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD OCT 27 PY 1997 VL 416 IS 3 BP 251 EP 253 DI 10.1016/S0014-5793(97)01211-8 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA YE704 UT WOS:A1997YE70400007 PM 9373163 ER PT J AU Chen, YD AF Chen, YD TI Asymmetric cycling and biased movement of Brownian particles in fluctuating symmetric potentials SO PHYSICAL REVIEW LETTERS LA English DT Article ID MOTION; RATCHETS AB Brownian particles can be induced to undergo biased movement by a fluctuating periodic potential, if the potential within each period is asymmetric. In this Letter, we show that similar phenomenon can be obtained even when the periodic potential is symmetric, if (i) there are at least three states for the potential to fluctuate, (ii) the extrema of the nonflat potentials are properly shifted, and (iii) the potential is fluctuating among the states in a cyclic way. We found that biased movement occurs only when net cycling is present and the direction of the movement is closely related to that of the net cycling, similar to the movement of a chemically driven enzyme particle in a static periodic potential. The formalism and the model can be used in studying the movement of a bead on a microtubule filament powered by a single one-headed kinesin. [S0031-9007(97)04385-8]. RP Chen, YD (reprint author), NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892, USA. NR 20 TC 22 Z9 22 U1 0 U2 2 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD OCT 27 PY 1997 VL 79 IS 17 BP 3117 EP 3120 DI 10.1103/PhysRevLett.79.3117 PG 4 WC Physics, Multidisciplinary SC Physics GA YC782 UT WOS:A1997YC78200006 ER PT J AU Richardson, JH Waldmann, TA Sodroski, JG Marasco, WA AF Richardson, JH Waldmann, TA Sodroski, JG Marasco, WA TI Inducible knockout of the interleukin-2 receptor alpha chain: Expression of the high-affinity IL-2 receptor is not required for the in vitro growth of HTLV-I-transformed cell lines SO VIROLOGY LA English DT Article ID LEUKEMIA-LYMPHOMA VIRUS; HUMAN T-CELLS; ANTI-TAC; INFECTED-CELLS; MESSENGER-RNA; BETA-CHAIN; LYMPHOCYTES; ANTIBODIES; ACTIVATION; DISTINCT AB Adult T cell leukemia (ATL) is an aggressive malignancy that is associated with HTLV-I infection and characterized by constitutive expression of the high-affinity interleukin-2 receptor. The cu subunit of the high-affinity receptor (IL-2R alpha), which is normally present only on activated T cells, is specifically upregulated by HTLV-I and constitutively expressed on fresh leukemic cells from ATL patients as well as cell lines transformed by HTLV-I in vitro. Here we directly address the functional significance of IL-2R alpha expression in HTLV-I transformed cell lines by using an endoplasmic reticulum-targeted single-chain antibody to inhibit the cell surface expression of IL-2 alpha. Using constitutive and tetracycline-repressible systems to express the ER-targeted antibody against IL-2R alpha, we have reduced cell surface expression of IL-2R alpha by more that 2 logs of mean fluorescence intensity to virtually undetectable levels in the IL-2-independent HTLV-I-transformed cell lines C8166-45 and HUT102. No toxicity was associated with the intracellular retention of IL-2R alpha, and the growth rate of the IL-2R alpha-negative cells was in each case comparable to that of the parental cell line. We conclude that cell surface expression of IL-2R alpha is dispensable for the in vitro growth of these HTLV-l-transformed cells. (C) 1997 Academic Press. C1 DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. NCI,METAB BRANCH,NIH,BETHESDA,MD 20892. NR 45 TC 14 Z9 16 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 0042-6822 J9 VIROLOGY JI Virology PD OCT 27 PY 1997 VL 237 IS 2 BP 209 EP 216 DI 10.1006/viro.1997.8779 PG 8 WC Virology SC Virology GA YF073 UT WOS:A1997YF07300003 PM 9356333 ER PT J AU Pastan, I AF Pastan, I TI Targeted therapy of cancer with recombinant immunotoxins SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Article DE immunotherapy; protein engineering ID STABILIZED FV FRAGMENT; PSEUDOMONAS EXOTOXIN; ANTITUMOR-ACTIVITY; INTERLEUKIN-2 RECEPTOR; COMPLETE REGRESSION; CHAIN IMMUNOTOXIN; HUMAN CARCINOMA; PHASE-I; T-CELL; MICE RP Pastan, I (reprint author), NCI,MOL BIOL LAB,DBS,NIH,BLDG 37,ROOM 4E16,37 CONVENT DR MSC 4255,BETHESDA,MD 20892, USA. NR 25 TC 42 Z9 46 U1 0 U2 2 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 OCT 24 PY 1997 VL 1333 IS 2 BP C1 EP C6 DI 10.1016/S0304-419X(97)00021-8 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA YG523 UT WOS:A1997YG52300007 PM 9395287 ER PT J AU Wang, YM Qin, ZH Nakai, M Chase, TN AF Wang, YM Qin, ZH Nakai, M Chase, TN TI Glutamate metabotropic receptor agonist 1S,3R-ACPD induces internucleosomal DNA fragmentation and cell death in rat striatum SO BRAIN RESEARCH LA English DT Article DE 1S,3R-ACPD; quinolinic acid; kainic acid; NMDA receptor; apoptosis; excitotoxicity; neurodegeneration ID METHYL-D-ASPARTATE; LONG-TERM POTENTIATION; CEREBELLAR GRANULE CELLS; CENTRAL-NERVOUS-SYSTEM; SYNAPTIC TRANSMISSION; MESSENGER-RNA; BRAIN INJURY; NEURODEGENERATIVE DISORDERS; GENE-EXPRESSION; NEURONAL INJURY AB Glutamate metabotropic receptor mediated mechanisms have been implicated in both neuroprotection and neurotoxicity. To characterize these mechanisms further in vivo, the effects of an intrastriatally injected metabotropic receptor agonist, trans-(1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid (1S,3R-ACPD), were studied alone and together with N-methyl-D-aspartate (NMDA) or kainic acid (KA) receptor agonists on DNA fragmentation and nerve cell death. 1S,3R-ACPD induced internucleosomal DNA fragmentation of striatal cells in a dose-dependent manner. TUNEL and propidium iodide staining showed DNA fragmentation and profound nuclear condensation around the injection site. Fragmented nuclei were occasionally seen under light microscopy. Internucleosomal DNA fragmentation induced by 1S,3R-ACPD was attenuated by the protein synthesis inhibitor cycloheximide as well as by the non-selective and selective metabotropic receptor antagonists L-(+)-2-amino-3-phosphonopionic acid (L-AP3), (RS)-aminoindan-1,5-dicarboxylic acid and (RS)-alpha-methylserine-o-phosphate monophenyl ester, respectively. The 1S,3R-ACPD (100-900 nmol) induced death of striatal neurons was suggested by the reduction in NMDA and D-1 clopamine receptors by up to 13% (P < 0.05) and 20% (P < 0.05) as well as by the decline in GAD(67) mRNA (25%, P < 0.01) and proenkephalin mRNA levels (35%, P < 0.01). Interestingly, IS,3R-ACPD attenuated internucleosomal DNA fragmentation induced by NMDA, but potentiated that induced by KA. These results suggest that metabotropic receptor stimulation leads to the death of striatal neurons by a mechanism having the biochemical stigmata of apoptosis. Moreover, metabotropic receptor stimulation evidently exerts opposite effects on pre- or postsynaptic mechanisms contributing to the NMDA and KA-induced apoptotic-like death of these neurons. (C) 1997 Elsevier Science B.V. C1 NINCDS,EXPT THERAPEUT BRANCH,NIH,BETHESDA,MD 20892. NR 59 TC 18 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 24 PY 1997 VL 772 IS 1-2 BP 45 EP 56 DI 10.1016/S0006-8993(97)00837-8 PG 12 WC Neurosciences SC Neurosciences & Neurology GA YG083 UT WOS:A1997YG08300006 PM 9406954 ER PT J AU Ren, B Thelen, AP Peters, JM Gonzalez, FJ Jump, DB AF Ren, B Thelen, AP Peters, JM Gonzalez, FJ Jump, DB TI Polyunsaturated fatty acid suppression of hepatic fatty acid synthase and S14 gene expression does not require peroxisome proliferator-activated receptor alpha SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RETINOID-X RECEPTOR; COA DESATURASE-1 GENE; HYDROGENATED FISH OIL; RAT-LIVER; BETA-OXIDATION; MESSENGER-RNA; CROSS-TALK; DIFFERENTIAL EXPRESSION; EICOSAPENTAENOIC ACID; SIGNALING PATHWAYS AB Dietary polyunsaturated fatty acids (PUFA) induce hepatic peroxisomal and microsomal fatty acid oxidation and suppress lipogenic gene expression. The peroxisome proliferator-activated receptor alpha (PPAR alpha) has been implicated as a mediator of fatty acid effects on gene transcription. This report uses the PPAR alpha-deficient mouse to examine the role of PPAR alpha in the PUFA regulation of mRNAs encoding hepatic lipogenic (fatty acid synthase (FAS) and the 514 protein (514)), microsomal (cytochrome P450 4A2 (CYP4A2)), and peroxisomal (acyl-CoA oxidase (AOX)) enzymes, PUFA ingestion induced mRNA(AOX) (2.3-fold) and mRNA(CYP4A2) (8-fold) and suppressed mRNA(FAS) and mRNA(S14) by greater than or equal to 80% in wild type mice, In PPAR alpha-deficient mice, PUFA did not induce mRNA(AOX) or mRNA(CYP4A2), indicating a requirement for PPAR alpha in the PUFA-mediated induction of these enzymes, However, PUFA still suppressed mRNA(FAS) and mRNA(S14) in the PPAR alpha-deficient mice, Studies in rats provided additional support for the differential regulation of lipogenic and peroxisomal enzymes by PUFA. These studies provide evidence for two distinct pathways for PUFA control of hepatic lipid metabolism. One requires PPAR alpha and is involved in regulating peroxisomal and microsomal enzymes, The other pathway does not require PPAR alpha and is involved in the PUFA mediated suppression of lipogenic gene expression. C1 MICHIGAN STATE UNIV,DEPT BIOCHEM,E LANSING,MI 48824. MICHIGAN STATE UNIV,DEPT PHYSIOL,E LANSING,MI 48824. NCI,LAB METAB,NIH,BETHESDA,MD 20892. RI Peters, Jeffrey/D-8847-2011 FU NIDDK NIH HHS [R01 DK043220] NR 52 TC 195 Z9 202 U1 1 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 OCT 24 PY 1997 VL 272 IS 43 BP 26827 EP 26832 DI 10.1074/jbc.272.43.26827 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YC659 UT WOS:A1997YC65900009 PM 9341113 ER PT J AU Asano, K Vornlocher, HP RichterCook, NJ Merrick, WC Hinnebusch, AG Hershey, JWB AF Asano, K Vornlocher, HP RichterCook, NJ Merrick, WC Hinnebusch, AG Hershey, JWB TI Structure of cDNAs encoding human eukaryotic initiation factor 3 subunits - Possible roles in RNA binding and macromolecular assembly SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAMMALIAN PROTEIN-SYNTHESIS; SACCHAROMYCES-CEREVISIAE; RABBIT RETICULOCYTES; TRANSLATIONAL INITIATION; FACTOR EIF-3; MOV-34 GENE; HELA-CELLS; COMPLEX; CLONING; YEAST AB The mammalian translation initiation factor 3 (eIF3), is a multiprotein complex of similar to 600 kDa that binds to the 40 S ribosome and promotes the binding of methionyl-tRNA(i) and mRNA. cDNA encoding 5 of the 10 subunits, namely eIF3-p170,-p116,-110,-p48, and -p36, have been isolated previously. Here we report the cloning and characterization of human cDNAs encoding the major RNA binding subunit, eIF3-p66, and two additional sub-units, eIF3-p47 and eIF3-p40. Each of these proteins is present in immunoprecipitates formed with affinity-purified anti-eIF3-p170 antibodies. Human eIF3-p66 shares 64% sequence identity with a hypothetical Caenorhabditis elegans protein, presumably the p66 homolog. Deletion analyses of recombinant derivatives of eIF3-p66 show that the RNA-binding domain lies within an N-terminal 71-amino acid region rich in lysine and arginine. The N-terminal regions of human eIF3-p40 and eIF3-p47 are related to each other and to 17 other erkaryotic proteins, including murine Mov-34, a subunit of the 26 S proteasome. Phylogenetic analyses of the 19 related protein sequences, called the Mov-34 family, distinguish five major subgroups, where eIF3-p40, eIF3-p47, and Mov-34 are each found in a different subgroup. The subunit composition of eIF3 appears to be highly conserved in Drosophila melanogaster, C. elegans, and Arabidopsis thaliana, whereas only 5 homologs of the 10 subunits of mammalian eIF3 are encoded in S. cerevisiae. C1 UNIV CALIF DAVIS,SCH MED,DEPT BIOL CHEM,DAVIS,CA 95616. CASE WESTERN RESERVE UNIV,SCH MED,DEPT BIOCHEM,CLEVELAND,OH 44106. NICHHD,LAB EUKARYOT GENE REGULAT,NIH,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM26796, GM22135, GM36467] NR 43 TC 133 Z9 146 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 OCT 24 PY 1997 VL 272 IS 43 BP 27042 EP 27052 DI 10.1074/jbc.272.43.27042 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YC659 UT WOS:A1997YC65900039 PM 9341143 ER PT J AU Aguilar, RC Ohno, H Roche, KW Bonifacino, JS AF Aguilar, RC Ohno, H Roche, KW Bonifacino, JS TI Functional domain mapping of the clathrin-associated adaptor medium chains mu 1 and mu 2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN SECONDARY STRUCTURE; COATED VESICLES; BINDING SUBUNIT; PLASMA-MEMBRANE; SORTING SIGNALS; AP-2 COMPLEXES; DELTA-COP; GOLGI; IDENTIFICATION; PREDICTION AB The clathrin-associated adaptors AP-1 and AP-2 are heterotetrameric complexes involved in the recognition of sorting signals present within the cytosolic domain of integral membrane proteins. The medium chains of these complexes, mu 1 and mu 2, have been implicated in two types of interaction: assembly with the beta 1 and beta 2 chains of the corresponding complexes and recognition of tyrosine-based sorting signals. In this study, we report the results of a structure-function analysis of the mu 1 and mu 2 chains aimed at identifying regions of the molecules that, ape responsible for each of the two interactions. Analyses using the yeast two-hybrid system and proteolytic digestion experiments suggest that mu 1 and mu 2 have a bipartite structure, with the amino-terminal one-third (residues 1-145 of mu 1 and mu 2) being involved in assembly with the beta chains and the carboxyl-terminal two-thirds (residues 147-423 of mu 1 and 164-435 of mu 2) binding tyrosine-based sorting signals, These observations support a model in which the amino-terminal one-third of mu 2 is embedded within the core of the AP-2 complex, while the carboxyl-terminal two-thirds of the protein are exposed to the medium, placing this region in a position to interact with tyrosine-based sorting signals. C1 NICHHD,CBMB,NIH,BETHESDA,MD 20892. RI Ohno, Hiroshi/L-7899-2014 OI Ohno, Hiroshi/0000-0001-8776-9661 NR 43 TC 64 Z9 64 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 OCT 24 PY 1997 VL 272 IS 43 BP 27160 EP 27166 DI 10.1074/jbc.272.43.27160 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YC659 UT WOS:A1997YC65900054 PM 9341158 ER PT J AU Ohya, K Kajigaya, S Yamashita, Y Miyazato, A Hatake, K Miura, Y Ikeda, U Shimada, K Ozawa, K Mano, H AF Ohya, K Kajigaya, S Yamashita, Y Miyazato, A Hatake, K Miura, Y Ikeda, U Shimada, K Ozawa, K Mano, H TI SOCS-1/JAB/SSI-1 can bind to and suppress Tec protein-tyrosine kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID X-LINKED AGAMMAGLOBULINEMIA; COLONY-STIMULATING FACTOR; CELL LINE; FAMILY; GENE; INTERLEUKIN-3; EXPRESSION; PHOSPHORYLATION; ERYTHROPOIETIN; ASSOCIATION AB Tec is the prototype of a recently emerging subfamily among nonreceptor type protein-tyrosine kinases and is known to become tyrosine-phosphorylated and activated by a wide range of cytokine stimulations in hematopoietic cells. Although Tec was recently shown to be involved in the cytokine-driven activation mechanism of c-fos transcription, it is yet obscure how Tec relays the signals from cell surface receptors to the nucleus. To identify signaling molecules: acting downstream of Tec, we have looked for Tec-interacting proteins (TIPs) by using the yeast two-hybrid system. Here we report the identification and characterization of a novel protein, TIP3, which has been simultaneously identified by other groups as SOCS-1, JAB, or SSI-l. TIP3 carries one Src homology 2 domain with a sequence similarity to that of CIS. In 293 cells, TIPB associates with Tec and suppresses its kinase activity. Interestingly, TIPB can also down-regulate the activity of Jak2 but not that of Lyn. We propose that SOCS-1/JAB/SSI-1/TIP3 is a novel type of negative regulator to a subset of protein-tyrosine kinases. C1 JICHI MED SCH, DEPT MOL BIOL, MINAMI KAWACHI, TOCHIGI 32904, JAPAN. JICHI MED SCH, DIV CARDIOL, MINAMI KAWACHI, TOCHIGI 32904, JAPAN. JICHI MED SCH, DIV HEMATOL, MINAMI KAWACHI, TOCHIGI 32904, JAPAN. NHLBI, HEMATOL BRANCH, NIH, BETHESDA, MD 20892 USA. NR 27 TC 92 Z9 96 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 OCT 24 PY 1997 VL 272 IS 43 BP 27178 EP 27182 DI 10.1074/jbc.272.43.27178 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YC659 UT WOS:A1997YC65900056 PM 9341160 ER PT J AU Herrera, JE Bergel, M Yang, XJ Nakatani, Y Bustin, M AF Herrera, JE Bergel, M Yang, XJ Nakatani, Y Bustin, M TI The histone acetyltransferase activity of human GCN5 and PCAF is stabilized by coenzymes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOSOMAL DNA; ACETYLATION; TRANSCRIPTION; H4; CHROMOSOME; CHROMATIN; YEAST; H3 AB Here we report that PCAF and human GCN5, two related type A histone acetyltransferases, are unstable enzymes that under the commonly used assay conditions are rapidly and irreversibly inactivated, Ire addition, we report that free histone H1, although not acetylated in vivo, is a preferred and convenient in vitro substrate for the study of PCAF, human GCN5, and possibly other type A histone acetyltransferases, Using either histone H1 or histone H3 as substrates, we find that preincubation with either acetyl-CoA or CoA stabilizes the acetyltransferase activities of PCAF, human GCN5 and an enzymatically active PCAF deletion mutant containing the C-terminal half of the protein. The stabilization requires the continuous presence of coenzyme, suggesting that the acetyltransferase-coenzyme complexes are stable, while the isolated apoenzymes are not, Human GCN5 and the N-terminal deletion mutant of PCAF are stabilized equally well by preincubation with either CoA or acetyl-CoA, while intact PCAF is better stabilized by acetyl-CoA than by CoA, Intact PCAF, but not the N-terminal truncation mutant or human GCN5, is auto-acetylated. These findings raise the possibility that the intracellular concentrations of the coenzymes affect the stability and therefore the nuclear activity of these acetyltransferases. C1 NICHHD,LAB MOL GROWTH REGULAT,NIH,BETHESDA,MD 20892. RP Herrera, JE (reprint author), NCI,MOL CARCINOGENESIS LAB,DIV BASIC SCI,NIH,BLDG 37,ROOM 3D-12,BETHESDA,MD 20892, USA. RI Bustin, Michael/G-6155-2015 NR 24 TC 42 Z9 42 U1 2 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 OCT 24 PY 1997 VL 272 IS 43 BP 27253 EP 27258 DI 10.1074/jbc.272.43.27253 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YC659 UT WOS:A1997YC65900067 PM 9341171 ER PT J AU Osipovich, O Durum, SK Muegge, K AF Osipovich, O Durum, SK Muegge, K TI Defining the minimal domain of Ku80 for interaction with Ku70 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; STRAND-BREAK-REPAIR; X-RAY RESISTANCE; V(D)J RECOMBINATION; AUTOANTIGEN-KU; DNA-BINDING; ANTIGEN; SUBUNIT; CELLS; CDNA AB The Ku protein has a critical function in the repair of double-strand DNA breaks induced for example by ionizing radiation or during VDJ recombination. Ku serves as the DNA-binding subunit of the DNA-dependent kinase and is a heterodimeric protein composed of 80- and 70-kDa subunits. We used the two hybrid system to analyze the interaction domains of the Ku subunits and to identify possible additional partners for Ku. Screening a human cDNA library with the Ku heterodimer did not reveal any novel partners. Screening with the individual subunits, we detected only Ku70 clones interacting with Ku80 and only Ku80 clones interacting with Ku70, indicating that these are the primary partners for one another. Ku80 and Ku70 formed only heterodimers and did not homodimerize. Ku80 was restricted to interacting with just one Ku70 molecule at a time. The minimal functional interaction domain of Ku80 that interacted with Ku70 was defined. It consisted of a 28-amino acid region extending from amino acid 449 to 477. This region was crucial for interaction with Ku70, since mutation within this critical site at amino acids 453 and 454 abrogated the ability to interact with Ku70. We furthermore verified that the same region is crucial for interaction with Ku70 using in vitro co-translation of both subunits followed by an immunoprecipitation with anti Ku70 antibodies. This interaction domain of Ku80 does not contain any motif previously recognized in protein-protein interactions. C1 NCI,FREDERICK CANC RES & DEV CTR,MOL IMMUNOREGULAT LAB,SAIC,INTRAMURAL RES SUPPORT PROGRAM,NIH,FREDERICK,MD 21702. NCI,MOL IMMUNOREGULAT LAB,NIH,FREDERICK,MD 21702. NR 40 TC 41 Z9 41 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 OCT 24 PY 1997 VL 272 IS 43 BP 27259 EP 27265 DI 10.1074/jbc.272.43.27259 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YC659 UT WOS:A1997YC65900068 PM 9341172 ER PT J AU Peters, JM Hennuyer, N Staels, B Fruchart, JC Fievet, C Gonzalez, FJ Auwerx, J AF Peters, JM Hennuyer, N Staels, B Fruchart, JC Fievet, C Gonzalez, FJ Auwerx, J TI Alterations in lipoprotein metabolism in peroxisome proliferator-activated receptor alpha-deficient mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID APOLIPOPROTEIN C-III; COENZYME-A OXIDASE; FATTY-ACIDS; GENE-EXPRESSION; PPAR; HYPERCHOLESTEROLEMIA; DIFFERENTIATION; FENOFIBRATE; INDUCTION; LIGAND AB The peroxisome proliferator-activated receptor-alpha (PPAR alpha) controls gene expression in response to a diverse class of compounds collectively referred to as peroxisome proliferators. Whereas most known peroxisome proliferators are of exogenous origin and include hypolipidemic drugs and other industrial chemicals, several endogenous PPAR alpha activators have been identified such as fatty acids and steroids, The latter finding and the fact that PPAR alpha modulates target genes encoding enzymes involved in lipid metabolism suggest a role for PPAR alpha in lipid metabolism, This was investigated in the PPAR alpha-deficient mouse model, Basal levels of total serum cholesterol, high density lipoprotein cholesterol, hepatic apolipoprotein A-I mRNA, and serum apolipoprotein A-I in PPAR alpha-deficient mice are significantly higher compared with wild type controls, Treatment with the fibrate Wy 14,643 decreased apoA-I serum levels and hepatic mRNA levels in wild-type mice, whereas no effect was detected in the PPAR alpha-deficient mice, Administration of the fibrate Wy 14,643 to wild-type mice results in marked depression of hepatic apolipoprotein C-III mRNA and serum triglycerides compared with un treated controls, In contrast, PPAR alpha-deficient mice were unaffected by Wy 14,643 treatment, These studies demonstrate that PPAR alpha modulates basal levels of serum cholesterol, in particular high density lipoprotein cholesterol, and establish that fibrate induced modulation in hepatic apolipoprotein A-I, C-III mRNA, and serum triglycerides observed in wild-type mice is mediated by PPAR alpha. C1 INST PASTEUR,U325 INSERM,DEPT ATHEROSCLEROSE,F-59019 LILLE,FRANCE. NCI,LAB METAB,NIH,BETHESDA,MD 20892. RI Peters, Jeffrey/D-8847-2011; Staels, Bart/N-9497-2016 OI Staels, Bart/0000-0002-3784-1503 NR 33 TC 334 Z9 343 U1 1 U2 6 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 OCT 24 PY 1997 VL 272 IS 43 BP 27307 EP 27312 DI 10.1074/jbc.272.43.27307 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YC659 UT WOS:A1997YC65900075 PM 9341179 ER PT J AU Croteau, DL apRhys, CMJ Hudson, EK Dianov, GL Hansford, RG Bohr, VA AF Croteau, DL apRhys, CMJ Hudson, EK Dianov, GL Hansford, RG Bohr, VA TI An oxidative damage-specific endonuclease from rat liver mitochondria SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FORMAMIDOPYRIMIDINE DNA GLYCOSYLASE; HAMSTER OVARY CELLS; ESCHERICHIA-COLI; CATALYTIC MECHANISM; FPG PROTEIN; SACCHAROMYCES-CEREVISIAE; SUBSTRATE-SPECIFICITY; IONIZING-RADIATION; BETA-ELIMINATION; REPAIR AB Reactive oxygen species have been shown to generate mutagenic lesions in DNA, One of the most abundant lesions in both nuclear and mitochondrial DNA is 7,8-dihydro-8-oxoguanine (8-oxoG). We report here the partial purification and characterization of a mitochondrial oxidative damage endonuclease (mtODE) from rat liver that recognizes and incises at 8-oxoG and abasic sites in duplex DNA. Rat liver mitochondria were purified by differential and Percoll gradient centrifugation, and mtODE was extracted from Triton X-100-solubilized mitochondria. Incision activity was measured using a radiolabeled double-stranded DNA oligonucleotide containing a unique 8-oxoG, and, reaction products were separated by polyacrylamide gel electrophoresis. Gel filtration chromatography predicts mtODE's molecular mass to be between 25 and 30 kDa. mtODE has a monovalent cation optimum between 50 and 100 mM KCl and a pH optimum between 7.5 and 8. mtODE does not require any co-factors and is active in the presence of 5 mM EDTA. It is specific for 8-oxoG and preferentially incises at S-oxoG:C base pairs. mtODE is a putative S-oxoG glycosylase/lyase enzyme, because it can be covalently linked to the 8-oxoG oligonucleotide by sodium borohydride reduction, Comparison of mtODE's activity with other known 8-oxoG glycosglases/lyases and mitochondrial enzymes reveals that this may be a novel protein. C1 NIA,MOL GENET LAB,NIH,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,DEPT PHARMACOL & MOL SCI,BALTIMORE,MD 21205. NR 49 TC 123 Z9 125 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 OCT 24 PY 1997 VL 272 IS 43 BP 27338 EP 27344 DI 10.1074/jbc.272.43.27338 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YC659 UT WOS:A1997YC65900080 PM 9341184 ER PT J AU Foger, B SantamarinaFojo, S Shamburek, RD Parrot, CL Talley, GD Brewer, HB AF Foger, B SantamarinaFojo, S Shamburek, RD Parrot, CL Talley, GD Brewer, HB TI Plasma phospholipid transfer protein - Adenovirus-mediated overexpression in mice leads to decreased plasma high density lipoprotein (HDL) and enhanced hepatic uptake of phospholipids and cholesteryl esters from HDL SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LIPID TRANSFER PROTEINS; APOLIPOPROTEIN-A-I; GENE; EXCHANGE; SUBPOPULATIONS; REPLACEMENT; CONVERSION; EXPRESSION; MECHANISM; VECTORS AB In vitro studies have shown that plasma phospholipid transfer protein (PLTP) converts isolated human high density lipoprotein-3 (HDL,) into larger HDL particles and generates lipid poor apoA-I containing nascent HDL, To evaluate the role of PLTP in vivo we generated recombinant adenovirus vectors containing either human PLTP cDNA (rPLTP.AdV) or the reporter luciferase cDNA as a control. After intravenous infusion of 4 x 10(7) plaque-forming units (low dose) and 4 x 10(8) plaque forming units (high dose) of rPLTP.AdV into mice, PLTP activity in plasma increased from base-line levels of 8.4 +/- 0.2 to 108 +/- 17 and from 8.9 +/- 0.6 to 352 +/- 31 mu mol/ml/h, respectively, on day 4 (both p < 0.001). Thus, both low and high doses of rPLTP.AdV led to pronounced overexpression of human PLTP in mice. On day 4 after treatment, mice treated with low and high doses of rPLTP.AdV showed decreased HDL cholesterol (-54% and -91%) and apoA-I (-64% and -98%) (all p < 0.05). Kinetic studies revealed that the fractional catabolic rates of HDL labeled with [H-3] phosphatidylcholine, [C-14]phosphatidylcholine ether, [H-3]cholesteryl ether, and I-125-labeled mouse apoA-I were increased by 8.5-, 8.7-, 3.8-, and 2.8-fold, respectively, in mice treated with low dose rPLTP.AdV (all p < 0.001). After injection of labeled HDL, mice treated with rPLTP.AdV showed an increased accumulation of labeled PC ether (+304%) and cholesteryl ether (+92%) in the liver (both p < 0.05), Two-dimensional gel electrophoresis of plasma 5 min after injection of HDL labeled with I-125 apoA-I demonstrated increased levels of newly generated pre-beta-HDL in mice overexpressing PLTP, In conclusion, HDL remodeling mediated by PLTP generates nascent, lipid-poor apoA-I in vivo and accelerates the hepatic uptake of HDL surface and core lipids in mice treated with rPLTP.AdV. Accelerated catabolism of HDL in mice overexpressing PLTP leads to low HDL levels. Our data indicate an important role for PLTP in modulating reverse cholesterol transport in vivo. RP Foger, B (reprint author), NHLBI,MOL DIS BRANCH,NIH,BLDG 10,ROOM 7N102,10 CTR DR,MSC 1666,BETHESDA,MD 20892, USA. NR 48 TC 121 Z9 123 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 OCT 24 PY 1997 VL 272 IS 43 BP 27393 EP 27400 DI 10.1074/jbc.272.43.27393 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YC659 UT WOS:A1997YC65900087 PM 9341191 ER PT J AU Takagi, Y Pause, A Conaway, RC Conaway, JW AF Takagi, Y Pause, A Conaway, RC Conaway, JW TI Identification of Elongin C sequences required for interaction with the von Hippel-Lindau tumor suppressor protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA-POLYMERASE-II; TRANSCRIPTION FACTOR-SIII; ELONGATION; ACTIVATION; COMPLEX AB Elongin C is a 112-amino acid protein that is found in mammalian cells as a positive regulatory subunit of heterotrimeric RNA polymerase ll elongation factor Elongin (Sill) and as a component of a multiprotein complex containing the von Hippel-Lindau (VHL) tumor suppressor protein, As a subunit of the Elongin complex, Elongin C interacts directly with the transcriptionally active Elongin A subunit and potently induces its elongation activity; in addition, Elongin C interacts with the ubiquitin-like Elongin B subunit, which regulates the interaction of Elongin C with Elongin A, As a component of the VHL complex, Elongin C interacts directly with both Elongin B and the VHL, protein. Binding of the VHL protein to Elongin C was found to prevent Elongin C from interacting with and activating. Elongin A in vitro, leading to the proposal that one function of the VHL protein may be to regulate RNA polymerase II elongation by negatively regulating the Elongin complex. In this report, we identify Elongin C sequences required for its interaction with the VHL protein, We previously demonstrated that the ability of Elongin C to hind and activate Elongin A is sensitive to mutations in the C-terminal half of Elongin C, as well as to mutations in an N-terminal Elongin C region needed for formation of the Elongin BC complex. Here we show that interaction of Elongin C with the VHL tumor suppressor protein depends strongly on sequences in the C terminus of Elongin C but is independent of the N-terminal Elongin C region required for binding to Elongin B and for binding and activation of Elongin A. Taken together, our results are consistent with the proposal that the VHL protein negatively regulates Elongin C activation of the Elongin complex by sterically blocking the interaction of C-terminal Elongin C sequences with Elongin A. In addition, our finding that only a subset of Elongin C sequences required for its interaction with Elongin A are critical for binding to VHL may offer the opportunity to develop reagents that selectively interfere with Elongin and VHL function. C1 OKLAHOMA MED RES FDN,PROGRAM MOL & CELL BIOL,OKLAHOMA CITY,OK 73104. UNIV OKLAHOMA,HLTH SCI CTR,DEPT BIOCHEM & MOL BIOL,OKLAHOMA CITY,OK 73190. NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892. OI Conaway, Joan/0000-0002-2786-0663 FU NIGMS NIH HHS [GM41628] NR 17 TC 9 Z9 9 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 OCT 24 PY 1997 VL 272 IS 43 BP 27444 EP 27449 DI 10.1074/jbc.272.43.27444 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YC659 UT WOS:A1997YC65900093 PM 9341197 ER PT J AU Linnekin, D DeBerry, CS Mou, S AF Linnekin, D DeBerry, CS Mou, S TI Lyn associates with the Juxtamembrane region of c-Kit and is activated by stem cell factor in hematopoietic cell lines and normal progenitor cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE KINASE; CYTOKINE SIGNAL-TRANSDUCTION; FACTOR-INDUCED PROLIFERATION; SRC-FAMILY KINASES; GROWTH-FACTOR; PROTOONCOGENE PRODUCT; AUTOIMMUNE-DISEASE; ESCHERICHIA-COLI; DEFICIENT MICE; RECEPTOR AB Stem cell factor (SCF) is a cytokine critical for normal hematopoiesis. The receptor for SCF is c-Kit, a receptor tyrosine kinase. Our laboratory is interested in delineating critical components of the SCF signal transduction pathway in hematopoietic tissue. The present study examines activation of Src family members in response to SCF. Stimulation of cell lines as well as normal progenitor cells with SCF rapidly increased tyrosine phosphorylation of the Src family member Lyn. Peak responses were noted 10-20 min after SCF treatment, and phosphorylation of Lyn returned to basal levels 60-90 min after stimulation, SCF also induced increases in Lyn kinase activity in, vitro. Lyn coimmunoprecipitated with c-Kit, and studies with GST fusion proteins demonstrated that Lyn readily associated with the juxtamembrane region of c-Kit. Treatment of cells with either Lyn antisense oligonucleotides or PPI, a Src family inhibitor, resulted in dramatic inhibition of SCF-induced proliferation. These data demonstrate that SCF rapidly activates Lyn and suggest that Lyn is critical in SCF-induced proliferation in hematopoietic cells. C1 NCI,FREDERICK CANC RES & DEV CTR,INTRAMURAL RES & SUPPORT PROGRAM,SAIC FREDERICK,FREDERICK,MD 21702. RP Linnekin, D (reprint author), NCI,FREDERICK CANC RES & DEV CTR,LAB LEUKOCYTE BIOL,DIV BASIC SCI,BLDG 567,RM 226,FREDERICK,MD 21702, USA. NR 40 TC 125 Z9 130 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 OCT 24 PY 1997 VL 272 IS 43 BP 27450 EP 27455 DI 10.1074/jbc.272.43.27450 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YC659 UT WOS:A1997YC65900094 PM 9341198 ER PT J AU Zeiger, E Erexson, G Mortelmans, K Thilagar, A AF Zeiger, E Erexson, G Mortelmans, K Thilagar, A TI Genetic toxicity studies of 1,2,3,4-tetrahydro-9-acridinamine (tacrine) SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE Salmonella typhimurium; ames test; CHO cells; chromosome aberration; bone marrow; micronucleus induction; cytogenetic effect; mutagenicity ID HAMSTER OVARY CELLS; MOUSE BONE-MARROW; HUMAN HEPATOCYTES; RAT; MUTAGENICITY; CYTOTOXICITY; BIOACTIVATION; ABERRATIONS; METABOLITES; MICROSOMES AB The mutagenicity and clastogenicity of 1,2,3,4-tetrahydro-9-acridinamine (tacrine) were studied in vitro using the Salmonella mutagenicity test and the induction of chromosome aberrations in Chinese hamster ovary (CHO) cells, and in the mouse bone marrow micronucleus test in vivo. This chemical is currently being used to treat dementia arising from Alzheimer's Disease, Tacrine was mutagenic in Salmonella but did not produce chromosome damage in CHO cells or in mouse bone marrow cells. A clear mutagenic response was seen in strain TA97 with rat and hamster liver S9; inconsistent results were obtained without S9, No mutagenicity was seen in strains TA98 and TA100 without S9, and inconsistent results were seen with S9. There was no induction of chromosome aberrations in cultured CHO cells with or without S9, Oral administration to mice of tacrine daily for three days did not result in the induction of micronuclei in their bone marrow cells. The mutagenic response in Salmonella, and the structure of the molecule, suggests that tacrine may be carcinogenic when tested in rodents. This information must be considered when preparing benefit-risk determinations for medical uses of this substance. (C) 1997 Elsevier Science B.V. C1 ENVIRONM HLTH RES & TESTING INC,LEXINGTON,KY. SRI INT,MENLO PK,CA 94025. SITEK,RES LABS,ROCKVILLE,MD. RP Zeiger, E (reprint author), NIEHS,EXPT TOXICOL BRANCH,RES TRIANGLE PK,NC 27709, USA. FU NIEHS NIH HHS [N01-ES-85223, N01-ES-75187, N01-ES-05286] NR 28 TC 9 Z9 9 U1 0 U2 0 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 OCT 24 PY 1997 VL 393 IS 3 BP 189 EP 197 DI 10.1016/S1383-5718(97)00096-X PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA YG311 UT WOS:A1997YG31100002 PM 9393611 ER PT J AU Zhou, Q Talaska, G Jaeger, M Bhatnagar, VK Hayes, RB Zenzer, TV Kashyap, SK Lakshmi, VM Kashyap, R Dosemeci, M Hsu, FF Parikh, DJ Davis, B Rothman, N AF Zhou, Q Talaska, G Jaeger, M Bhatnagar, VK Hayes, RB Zenzer, TV Kashyap, SK Lakshmi, VM Kashyap, R Dosemeci, M Hsu, FF Parikh, DJ Davis, B Rothman, N TI Benzidine-DNA adduct levels in human peripheral white blood cells significantly correlate with levels in exfoliated urothelial cells SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE white blood cells; exfoliated urothelial cells; benzidine; DNA adduct; biomonitoring ID EXPOSED WORKERS; BLADDER-CANCER; METABOLISM; SMOKERS; SMOKING; DYES AB In a cross-sectional study of 33 workers exposed to benzidine and benzidine dyes and 15 non-exposed controls, we previously reported that exposure status and internal dose of benzidine metabolites were strongly correlated with the levels of specific benzidine-DNA adducts in exfoliated urothelial cells. We also evaluated DNA adduct levels in peripheral white blood cells (WBC) of a subset of Is exposed workers and 7 controls selected to represent a wide range of adducts in exfoliated urothelial cells. Samples were coded and then DNA was analyzed using P-32-postlabeling, along with n-butanol extraction. One adduct, which co-chromatographed with a synthetic N-(3'-phospho-deoxyguanosin-8-yl)-N'-acetylbenzidine standard, predominated in those samples with adducts present. The median level (range) of this adduct in WBC DNA was 194.4 (3.2-975) RAL X 10(9) in exposed workers and 1.4 (0.1-6.4) in the control subjects (p = 0.0002, Wilcoxon Rank Sum Test). There was a striking correlation between WBC and exfoliated urothelial cell adduct levels (Pearson r = 0.84, p < 0.001) among exposed subjects. In addition, the sum of urinary benzidine, N-acetylbenzidine and N,N'-diacetylbenzidine correlated with the levels of this adduct in both tissues. This is the first study in humans to show a relationship for a specific carcinogen adduct in a surrogate tissue and in urothelial cells, the target for urinary bladder cancer. (C) 1997 Elsevier Science B.V. C1 UNIV CINCINNATI,DEPT ENVIRONM HLTH,CINCINNATI,OH 45267. NATL INST OCCUPAT HLTH,AHMEDABAD,GUJARAT,INDIA. NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. VET ADM MED CTR,ST LOUIS,MO 63125. ST LOUIS UNIV,MED CTR,ST LOUIS,MO 63125. FU NIEHS NIH HHS [I-P30-ESO6096-01]; PHS HHS [Q601263MQ527262-01] NR 20 TC 30 Z9 30 U1 0 U2 1 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 OCT 24 PY 1997 VL 393 IS 3 BP 199 EP 205 DI 10.1016/S1383-5718(97)00097-1 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA YG311 UT WOS:A1997YG31100003 PM 9393612 ER PT J AU Hieter, P Boguski, M AF Hieter, P Boguski, M TI Functional genomics: It's all how you read it SO SCIENCE LA English DT Editorial Material ID GENE-EXPRESSION; STRATEGY C1 NIH,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20892. RP Hieter, P (reprint author), UNIV BRITISH COLUMBIA,DEPT MED GENET,CTR MOL MED & THERAPEUT,VANCOUVER,BC V6T 124,CANADA. NR 18 TC 197 Z9 232 U1 2 U2 13 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 24 PY 1997 VL 278 IS 5338 BP 601 EP 602 DI 10.1126/science.278.5338.601 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YC323 UT WOS:A1997YC32300036 PM 9381168 ER PT J AU Tatusov, RL Koonin, EV Lipman, DJ AF Tatusov, RL Koonin, EV Lipman, DJ TI A genomic perspective on protein families SO SCIENCE LA English DT Article ID ARCHAEON METHANOSARCINA-THERMOPHILA; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; PHYLOGENETIC TREES; CARBONIC-ANHYDRASE; BACTERIAL GENOMES; SEQUENCE-ANALYSIS; BINDING; GENES; SIMILARITY AB In order to extract the maximum amount of information from the rapidly accumulating genome sequences, all conserved genes need to be classified according to their homologous relationships. Comparison of proteins encoded in seven complete genomes from five major phylogenetic lineages and elucidation of consistent patterns of sequence similarities allowed the delineation of 720 clusters of orthologous groups (COGs). Each COG consists of individual orthologous proteins or orthologous sets of paralogs from at least three lineages. Orthologs typically have the same function, allowing transfer of functional information from one member to an entire COG. This relation automatically yields a number of functional predictions for poorly characterized genomes. The COGs comprise a framework for functional and evolutionary genome analysis. C1 NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20894. NR 63 TC 2043 Z9 2113 U1 13 U2 95 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 24 PY 1997 VL 278 IS 5338 BP 631 EP 637 DI 10.1126/science.278.5338.631 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YC323 UT WOS:A1997YC32300041 PM 9381173 ER PT J AU Abashkin, YG Burt, SK Russo, N AF Abashkin, YG Burt, SK Russo, N TI Density functional study of the mechanisms and the potential energy surfaces of MCH2++H-2 reactions. The case of cobalt and rhodium (M = Co, Rh) SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Article ID TRANSITION-METAL IONS; GAS-PHASE; AB-INITIO; ORGANOMETALLIC CHEMISTRY; GEOMETRICAL STRUCTURES; ELECTRONIC-STRUCTURE; METHANE ACTIVATION; SMALL ALKANES; COMPLEXES; OPTIMIZATION AB The potential energy surfaces for the reactions MCH2+ + H-2 --> M+ + CH4 (M = Co, Rh) have been studied by means of a density functional approach in which we considered both the singlet and triplet state channels. The H-H bond cleavage in the singlet state follows a stepwise H-2 Splitting corresponding to an oxidative hydrogen addition mechanism; while for the triplet state only a concerted mechanism with the formation of a four-center transition state structure is possible. For the reaction involving Co+ cation, the triplet channel is energetically favored at the beginning and at the end of the reaction, although the barrier height for the H-2 activation is much lower in the excited singlet path. However, the energetic penalty required to obtain the singlet excited state is prohibitive and precludes this pathway as a channel for this reaction. Thus, we conclude that this reaction (M = Co+) follows a four-center mechanism in the triplet state. On the basis of our results we conclude that the RhCH2+ + H-2 --> Rh+ + CH4 reaction should be a spin-forbidden process. The reaction starts in the singlet ground state and follows through an oxidative addition mechanism of H-2 to the Rh+ moiety of the RhCH2+ compound. Further shift of the hydrogen atom toward the carbon leads to formation of the hydride-methyl complex (HRhCH3+). Changing of the singlet spin state probably occurs immediately after formation of the HRhCH3+ intermediate. This intermediate in the triplet state is metastable and collapses to the final complex without any barrier. Our results for both considered reactions are in good agreement with available experimental data. C1 UNIV CALABRIA, DIPARTIMENTO CHIM, I-87030 ARCAVACATA, ITALY. RP NCI, FREDERICK CANC RES & DEV CTR, STRUCT BIOCHEM PROGRAM, FREDERICK BIOMED SUPERCOMP CTR, SAIC, FREDERICK, MD 21702 USA. OI Nino, Russo/0000-0003-3826-3386 NR 48 TC 27 Z9 27 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5639 J9 J PHYS CHEM A JI J. Phys. Chem. A PD OCT 23 PY 1997 VL 101 IS 43 BP 8085 EP 8093 DI 10.1021/jp970611m PG 9 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA YD603 UT WOS:A1997YD60300025 ER PT J AU PerezSchael, I Guntinas, MJ Perez, M Pagone, V Rojas, AM Gonzalez, R Cunto, W Hoshino, Y Kapikian, AZ AF PerezSchael, I Guntinas, MJ Perez, M Pagone, V Rojas, AM Gonzalez, R Cunto, W Hoshino, Y Kapikian, AZ TI Efficacy of the rhesus rotavirus-based quadrivalent vaccine in infants and young children in Venezuela SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID LINKED IMMUNOSORBENT-ASSAY; ESCHERICHIA-COLI; INFECTION; STRAINS; IMMUNOGENICITY; REACTOGENICITY; RESPONSES; SAFETY AB Background Rotaviruses are the principal known etiologic agents of severe diarrhea among infants and young children worldwide. Although a rhesus rotavirus-based quadrivalent vaccine is highly effective in preventing severe diarrhea in developed countries, in developing countries its efficacy has been less impressive. We thus conducted a catchment study in Venezuela to assess the efficacy of the vaccine against dehydrating diarrhea. Methods In this randomized, double-blind, placebo-controlled trial, 2207 infants received three oral doses of the quadrivalent rotavirus vaccine (4x10(5) plaque-forming units per dose) or placebo at about two, three, and four months of age. During approximately 19 to 20 months of passive surveillance, episodes of gastroenteritis were evaluated at the hospital. Results The vaccine was safe, although 15 percent of the vaccinated infants had febrile episodes (rectal temperature, greater than or equal to 38.1 degrees C) during the six days after the first dose, as compared with 7 percent of the controls (P<0.001). However, the vaccine gave 88 percent protection against severe diarrhea caused by rotavirus and 75 percent protection against dehydration, and produced a 70 percent reduction in hospital admissions. Overall, the efficacy of the vaccine against a first episode of rotavirus diarrhea was 48 percent, Horizontal transmission of vaccine virus was demonstrated in 15 percent of the vaccine recipients and 13 percent of the placebo recipients with rotavirus-positive diarrhea. Conclusions In this study in a developing country, the quadrivalent rhesus rotavirus-based vaccine induced a high level of protection against severe diarrheal illness caused by rotavirus. (C) 1997, Massachusetts Medical Society. C1 CENT UNIV VENEZUELA,MINIST SANIDAD,INST BIOMED,SECC INVEST ENFERMEDADES ENTER,FUVESIN,CARACAS,VENEZUELA. INST BIOMED VENEZUELA,CARACAS,VENEZUELA. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. FU NHLBI NIH HHS [BST5947-P-HI-4265]; PHS HHS [87-I-113] NR 40 TC 237 Z9 248 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 OCT 23 PY 1997 VL 337 IS 17 BP 1181 EP 1187 DI 10.1056/NEJM199710233371701 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA YB718 UT WOS:A1997YB71800001 PM 9337376 ER PT J AU Small, GW Rabins, PV Barry, PP Buckholtz, NS DeKosky, ST Ferris, SH Finkel, SI Gwyther, LP Khachaturian, ZS Lebowitz, BD McRae, TD Morris, JC Oakley, F Schneider, LS Streim, JE Sunderland, T Teri, LA Tune, LE AF Small, GW Rabins, PV Barry, PP Buckholtz, NS DeKosky, ST Ferris, SH Finkel, SI Gwyther, LP Khachaturian, ZS Lebowitz, BD McRae, TD Morris, JC Oakley, F Schneider, LS Streim, JE Sunderland, T Teri, LA Tune, LE TI Diagnosis and treatment of Alzheimer disease and related disorders - Consensus statement of the American Association for Geriatric Psychiatry, the Alzheimer's Association, and the American Geriatrics Society SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; NURSING-HOME PLACEMENT; BEHAVIORAL SYMPTOMS; CLINICAL-DIAGNOSIS; SENILE DEMENTIA; OLDER PATIENTS; PREVALENCE; TACRINE; CARE; GENE AB Objective.-A consensus conference on the diagnosis and treatment of Alzheimer disease (AD) and related disorders was organized by the American Association for Geriatric Psychiatry, the Alzheimer's Association, and the American Geriatrics Society on January 4 and 5, 1997, The target audience was primary care physicians, and the following questions were addressed: (1) How prevalent is AD and what are its risk factors? What is its impact on society? (2) What are the different forms of dementia and how can they be recognized? (3) What constitutes safe and effective treatment for AD? What are the indications and contraindications for specific treatments? (4) What management strategies are available to the primary care practitioner? (5) What are the available medical specialty and community resources? (6) What are the important policy issues and how can policymakers improve access to care for dementia patients? (7) What are the most promising questions for future research? Participants.-Consensus panel members and expert presenters were drawn from psychiatry, neurology, geriatrics, primary care, psychology, nursing, social work, occupational therapy, epidemiology, and public health and policy. Evidence.-The expert presenters summarized data from the world scientific literature on the questions posed to the panel. Consensus Process.-The panelists listened to the experts' presentations, reviewed their background papers, and then provided responses to the questions based on these materials, The panel chairs prepared the initial drafts of the consensus statement, and these drafts were read by all panelists and edited until consensus was reached. Conclusions.-Alzheimer disease is the most common disorder causing cognitive decline in old age and exacts a substantial cost on society, Although the diagnosis of AD is often missed or delayed, it is primarily one of inclusion, not exclusion, and usually can be made using standardized clinical criteria, Most cases can be diagnosed and managed in primary care settings, yet some patients with atypical presentations, severe impairment, or complex comorbidity benefit from specialist referral, Alzheimer disease is progressive and irreversible, but pharmacologic therapies for cognitive impairment and nonpharmacologic and pharmacologic treatments for the behavioral problems associated with dementia can enhance quality of life, Psychotherapeutic intervention with family members is often indicated, as nearly half of all caregivers become depressed, Health care delivery to these patients is fragmented and inadequate, and changes in disease management models are adding stresses to the system, New approaches are needed to ensure patients' access to essential resources, and future research should aim to improve diagnostic and therapeutic effectiveness. C1 JOHNS HOPKINS UNIV, BALTIMORE, MD USA. BOSTON UNIV, BOSTON, MA 02215 USA. NIA, BETHESDA, MD 20892 USA. UNIV PITTSBURGH, PITTSBURGH, PA USA. NYU, NEW YORK, NY USA. NORTHWESTERN UNIV, CHICAGO, IL 60611 USA. DUKE UNIV, DURHAM, NC USA. RONALD & NANCY REAGAN RES INST, BETHESDA, MD USA. NIMH, BETHESDA, MD 20892 USA. WASHINGTON UNIV, ST LOUIS, MO USA. NIH, BETHESDA, MD 20892 USA. UNIV SO CALIF, LOS ANGELES, CA USA. UNIV PENN, PHILADELPHIA, PA 19104 USA. UNIV WASHINGTON, SEATTLE, WA 98195 USA. WESLEY WOODS GERIATR HOSP, ATLANTA, GA USA. RP Small, GW (reprint author), UNIV CALIF LOS ANGELES, NEUROPSYCHIAT INST & HOSP, 760 WESTWOOD PLAZA, ROOM 37-432, LOS ANGELES, CA 90024 USA. RI Morris, John/A-1686-2012 NR 86 TC 617 Z9 630 U1 8 U2 95 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 22 PY 1997 VL 278 IS 16 BP 1363 EP 1371 DI 10.1001/jama.278.16.1363 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA YA905 UT WOS:A1997YA90500039 PM 9343469 ER PT J AU Wetle, T AF Wetle, T TI Living longer, aging better - Aging research comes of age SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP Wetle, T (reprint author), NIA,BLDG 31,RM 5C35,31 CTR DR,MSC 2292,BETHESDA,MD 20892, USA. NR 11 TC 9 Z9 9 U1 3 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 OCT 22 PY 1997 VL 278 IS 16 BP 1376 EP 1377 DI 10.1001/jama.278.16.1376 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA YA905 UT WOS:A1997YA90500042 PM 9343472 ER PT J AU Russell, MWW Baker, PB Brody, LC Izumo, S AF Russell, MWW Baker, PB Brody, LC Izumo, S TI Expression pattern and chromosomal localization of the human dHAND and eHAND genes, two basic helix-loop-helix proteins primarily expressed in the heart SO CIRCULATION LA English DT Meeting Abstract C1 UNIV MICHIGAN,ANN ARBOR,MI 48109. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 74 EP 74 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000074 ER PT J AU Kuller, LH Bryan, RN Burke, G Bhadelia, R Fried, LP Haan, MN Manolio, TA Shemanski, L Tracy, RP AF Kuller, LH Bryan, RN Burke, G Bhadelia, R Fried, LP Haan, MN Manolio, TA Shemanski, L Tracy, RP TI Relationship between MRI abnormalities, stroke, APOE, and modified mini-mental state score (3MSE) in the cardiovascular health study SO CIRCULATION LA English DT Meeting Abstract C1 UNIV PITTSBURGH,PITTSBURGH,PA 15260. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. TUFTS UNIV,NEW ENGLAND MED CTR,BOSTON,MA 02111. UNIV CALIF,SACRAMENTO,CA. NIH,BETHESDA,MD 20892. CHS COORDINATING CTR,SEATTLE,WA. UNIV VERMONT,COLCHESTER,VT. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 186 EP 186 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000186 ER PT J AU Haudenschild, CC Dugi, KA Amar, MJ Knapper, CL Bensadoun, A Maeda, N Brewer, HB SantamarinaFojo, S AF Haudenschild, CC Dugi, KA Amar, MJ Knapper, CL Bensadoun, A Maeda, N Brewer, HB SantamarinaFojo, S TI Identification of a residue (433K) essential for hepatic lipase mediated remnant lipoprotein metabolism independent of lipolysis SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. CORNELL UNIV,NEW YORK,NY. UNIV N CAROLINA,CHAPEL HILL,NC 27515. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 201 EP 201 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000201 ER PT J AU Speir, E Yu, ZX Cannon, RO AF Speir, E Yu, ZX Cannon, RO TI Estrogen inhibits free radical generation, viral promoter activity and viral replication induced by cytomegalovirus infection of human smooth muscle cells SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 239 EP 239 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000239 ER PT J AU Liang, BT Jacobson, KA AF Liang, BT Jacobson, KA TI Differential cardioprotective effects mediated by cardiac myocyte adenosine A1 and A3 receptors. SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. UNIV PENN,PHILADELPHIA,PA 19104. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 286 EP 286 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000285 ER PT J AU Stambaugh, K Jacobson, KA Liang, BT AF Stambaugh, K Jacobson, KA Liang, BT TI Novel cardioprotective functions of activated adenosine A1 and A3 receptors and attenuated A2A receptor during prolonged simulated ischemia. SO CIRCULATION LA English DT Meeting Abstract C1 UNIV PENN,MED CTR,PHILADELPHIA,PA 19104. NIH,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 289 EP 289 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000294 ER PT J AU Nakayama, H Kuniyasu, A Itagaki, K Shibano, T Iino, M Kraft, G Schwartz, A AF Nakayama, H Kuniyasu, A Itagaki, K Shibano, T Iino, M Kraft, G Schwartz, A TI Identification of the binding region of semotiadil, a new modulator of the L-type calcium channel. SO CIRCULATION LA English DT Meeting Abstract C1 KUMAMOTO UNIV,KUMAMOTO 860,JAPAN. NIEHS,RES TRIANGLE PK,NC 27709. DAIICHI PHARMACEUT CO LTD,TOKYO 134,JAPAN. UNIV CINCINNATI,CINCINNATI,OH 45221. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 300 EP 300 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000299 ER PT J AU White, CW Campeau, L Knatterud, G Forrester, JS Gobel, F Hard, JA Domanski, MJ Hoogwerf, B Canner, J Rosenberg, Y Hunninghake, D AF White, CW Campeau, L Knatterud, G Forrester, JS Gobel, F Hard, JA Domanski, MJ Hoogwerf, B Canner, J Rosenberg, Y Hunninghake, D TI Effect of an aggressive lipid lowering strategy on progression of atherosclerosis at the saphenous vein graft (SVG) distal native vessel (NV) anastomosis SO CIRCULATION LA English DT Meeting Abstract C1 UNIV MINNESOTA,MINNEAPOLIS,MN. MONTREAL HEART INST,MONTREAL,PQ H1T 1C8,CANADA. MARYLAND MED RES INST,BALTIMORE,MD. CEDARS SINAI MED CTR,LOS ANGELES,CA 90048. MINNEAPOLIS HEART INST,MINNEAPOLIS,MN. BAYLOR COLL MED,HOUSTON,TX 77030. NHLBI,BETHESDA,MD 20892. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 356 EP 356 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000355 ER PT J AU Kitsiou, AN Bacharach, SL Srinivasan, G Davis, CM Nour, KA Dilsizian, V AF Kitsiou, AN Bacharach, SL Srinivasan, G Davis, CM Nour, KA Dilsizian, V TI Myocardial blood flow during low dose dobutamine infusion: Relation to thallium uptake in asynergic regions SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 367 EP 367 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000366 ER PT J AU Larsen, GC McAnulty, JH Hallstrom, A Marchant, C Shein, M Akiyama, T Brodsky, M Baessler, C Pinski, SL Jennings, CA Morris, M AF Larsen, GC McAnulty, JH Hallstrom, A Marchant, C Shein, M Akiyama, T Brodsky, M Baessler, C Pinski, SL Jennings, CA Morris, M TI Hospitalization charges in the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial: The AVID economic analysis study SO CIRCULATION LA English DT Meeting Abstract C1 PORTLAND VA MED CTR,PORTLAND,OR. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. UNIV WASHINGTON,SEATTLE,WA 98195. US FDA,ROCKVILLE,MD 20857. UNIV ROCHESTER,ROCHESTER,NY. UNIV CALIF,ORANGE,CA. MED COLL PENN & HAHNEMANN UNIV,LIKOFF INST,PHILADELPHIA,PA. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. NATL INST HLTH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 424 EP 424 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000423 ER PT J AU Wilkoff, BL Shih, HT Friedman, PL Page, RL Klein, RC Dalamagas, H Nora, M Larsen, GC Baessler, C Morris, M Jennings, C AF Wilkoff, BL Shih, HT Friedman, PL Page, RL Klein, RC Dalamagas, H Nora, M Larsen, GC Baessler, C Morris, M Jennings, C TI Multivariate predictors of hospital length of stay in patients with severe ventricular arrhythmias: Antiarrhythmics versus implantable defibrillators registry study SO CIRCULATION LA English DT Meeting Abstract C1 CLEVELAND CLIN FDN,CLEVELAND,OH 44195. UNIV TEXAS,HOUSTON,TX. HARVARD UNIV,BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. UNIV TEXAS,DALLAS,TX 75230. UNIV UTAH,SALT LAKE CITY,UT. ST FRANCIS HOSP & MED CTR,HARTFORD,OH. MIDWEST HEART SPECIALISTS,LOMBARD,IL. PORTLAND VA MED CTR,PORTLAND,OR. MED COLL PENN & HAHNEMANN UNIV,LIKOFF INST,PHILADELPHIA,PA. UNIV WASHINGTON,SEATTLE,WA 98195. NHLBI,WASHINGTON,DC. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 425 EP 425 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000430 ER PT J AU Vaitkevicius, PV Ebersold, C Haydar, Z Stewart, KJ Fleg, JL AF Vaitkevicius, PV Ebersold, C Haydar, Z Stewart, KJ Fleg, JL TI The utility of exercise training to improve functional capacity of elderly heart failure patients SO CIRCULATION LA English DT Meeting Abstract C1 JOHNS HOPKINS,BALTIMORE,MD. BAYLOR UNIV,MED CTR,DALLAS,TX. NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 465 EP 465 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000464 ER PT J AU Talbot, LA Metter, EJ Fleg, JL AF Talbot, LA Metter, EJ Fleg, JL TI Relationship between leisure time physical activity and cardiorespiratory fitness in healthy adults SO CIRCULATION LA English DT Meeting Abstract C1 TCU,HIA,NINRR,FT WORTH,TX. NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 470 EP 470 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000469 ER PT J AU Kitsiou, AN Bacharach, SL Srinivasan, G Davis, CM Nour, KA Quyyumi, AA Dilsizian, V AF Kitsiou, AN Bacharach, SL Srinivasan, G Davis, CM Nour, KA Quyyumi, AA Dilsizian, V TI The majority of asynergic regions with abnormal myocardial blood flow response during low dose dobutamine infusion are viable by thallium. SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 501 EP 501 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000500 ER PT J AU Folsom, AR Nieto, FJ Sorlie, P Chambless, LE Graham, DY AF Folsom, AR Nieto, FJ Sorlie, P Chambless, LE Graham, DY TI No association of Helicobacter pylori seropositivity with coronary heart disease in a prospective study. SO CIRCULATION LA English DT Meeting Abstract C1 UNIV MINNESOTA,MINNEAPOLIS,MN 55455. JOHNS HOPKINS,BALTIMORE,MD. NHLBI,BETHESDA,MD 20892. COLLABORAT STUDIES COORDINATING CTR,CHAPEL HILL,NC. BAYLOR COLL MED,HOUSTON,TX 77030. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 545 EP 545 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000544 ER PT J AU Sakkinen, PA Cushman, M Kuller, LH Psaty, BM Rodriguez, BL Boineau, R Tracy, RP AF Sakkinen, PA Cushman, M Kuller, LH Psaty, BM Rodriguez, BL Boineau, R Tracy, RP TI Correlates of plasmin-alpha 2-antiplasmin in two elderly cohorts. SO CIRCULATION LA English DT Meeting Abstract C1 UNIV VERMONT,BURLINGTON,VT 05405. UNIV PENN,PITTSBURGH,PA. UNIV WASHINGTON,SEATTLE,WA 98195. HONOLULU HEART PROGRAM,HONOLULU,HI. NIH,WASHINGTON,DC. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 547 EP 547 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000546 ER PT J AU Cushman, M Kuller, LH Lemaitre, RN Psaty, BM Sharrett, ARR Tracy, RP AF Cushman, M Kuller, LH Lemaitre, RN Psaty, BM Sharrett, ARR Tracy, RP TI Plasmin generation and risk of incident cardiovascular disease in the elderly. SO CIRCULATION LA English DT Meeting Abstract C1 UNIV VERMONT,COLCHESTER,VT. UNIV PITTSBURGH,PITTSBURGH,PA 15260. UNIV WASHINGTON,SEATTLE,WA 98195. NHLBI,BETHESDA,MD 20892. UNIV VERMONT,BURLINGTON,VT 05405. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 548 EP 548 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000547 ER PT J AU Tracy, RP Psaty, BM Tang, ZH Lemaitre, RN Kuller, LH Mann, KG Sharrett, AR Yandell, DW AF Tracy, RP Psaty, BM Tang, ZH Lemaitre, RN Kuller, LH Mann, KG Sharrett, AR Yandell, DW TI Coagulation factor V genetic polymorphisms associated with cardiovascular disease in the elderly. SO CIRCULATION LA English DT Meeting Abstract C1 UNIV VERMONT,COLCHESTER,VT. UNIV WASHINGTON,SEATTLE,WA 98195. UNIV PITTSBURGH,PITTSBURGH,PA 15260. UNIV VERMONT,BURLINGTON,VT 05405. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 549 EP 549 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000548 ER PT J AU Cardillo, C Kilcoyne, CM Quyyumi, AA Cannon, RO Panza, JA AF Cardillo, C Kilcoyne, CM Quyyumi, AA Cannon, RO Panza, JA TI Nitric oxide-dependent vasodilator response to systemic but not to local hyperinsulinemia in the human forearm. SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 564 EP 564 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000552 ER PT J AU Amar, MJ Vaisman, BL Foger, B Paigen, B Talley, GD Brewer, HB SantamarinaFojo, S AF Amar, MJ Vaisman, BL Foger, B Paigen, B Talley, GD Brewer, HB SantamarinaFojo, S TI The effect of hepatic lipase deficiency on the plasma lipids, lipoproteins and diet-induced atherosclerosis in LCAT transgenic mice SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. JACKSON LAB,BAR HARBOR,ME 04609. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 611 EP 611 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000598 ER PT J AU Foger, B Vaisman, BL Paigen, B Hoyt, RF Brewer, HB SantamarinaFojo, S AF Foger, B Vaisman, BL Paigen, B Hoyt, RF Brewer, HB SantamarinaFojo, S TI Cetp modulates the development of aortic atherosclerosis in Lcat-transgenic mice SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. JACKSON LAB,BAR HARBOR,ME 04609. NHLBI,LAMS,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 613 EP 613 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000606 ER PT J AU Zhang, WY Gaynor, PM Kruth, HS AF Zhang, WY Gaynor, PM Kruth, HS TI Aggregated LDL induces and enters surface-connected compartments of human monocyte-macrophages: A process independent of the LDL receptor SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 624 EP 624 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000611 ER PT J AU Long, XL Crow, MT ONeil, L Sollott, SJ Menees, DS Boluyt, MO Lakatta, EG AF Long, XL Crow, MT ONeil, L Sollott, SJ Menees, DS Boluyt, MO Lakatta, EG TI Blockade of vacuolar proton ATPase induces p53-mediated apoptosis in neonatal rat cardiomyocytes SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 649 EP 649 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000640 ER PT J AU Segura, AM Luna, RE Horiba, K StetlerStevenson, WG McAllister, HA Willerson, JT Ferrans, VJ AF Segura, AM Luna, RE Horiba, K StetlerStevenson, WG McAllister, HA Willerson, JT Ferrans, VJ TI Immunohistochemistry of matrix metalloproteinases and their inhibitors in thoracic aortic SO CIRCULATION LA English DT Meeting Abstract C1 TEXAS HEART INST,HOUSTON,TX 77025. NIH,BETHESDA,MD 20892. UNIV TEXAS,HOUSTON,TX. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 706 EP 706 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000693 ER PT J AU Goff, DC Feldman, HA McGovern, PG Goldberg, RJ Cornell, CE Hedges, JR Cooper, LS Osganian, SK SimonsMorton, DG AF Goff, DC Feldman, HA McGovern, PG Goldberg, RJ Cornell, CE Hedges, JR Cooper, LS Osganian, SK SimonsMorton, DG TI Prehospital delay in patients hospitalized with myocardial infarction symptoms in the US: REACT SO CIRCULATION LA English DT Meeting Abstract C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC 27109. NEW ENGLAND RES INST,WATERTOWN,MA 02172. UNIV MINNESOTA,MINNEAPOLIS,MN. UNIV MASSACHUSETTS,WORCESTER,MA 01605. UNIV ALABAMA,BIRMINGHAM,AL. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 874 EP 874 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000874 ER PT J AU Li, ZH Froehlich, JP Galis, ZS Lakatta, EG AF Li, ZH Froehlich, JP Galis, ZS Lakatta, EG TI Age-associated accumulation of matrix metalloproteinase-2 (MMP-2) within the rat aortic wall and increased MMP-2 production by vascular smooth muscle cells SO CIRCULATION LA English DT Meeting Abstract C1 NIA,CARDIOVASC SCI LAB,NIH,BALTIMORE,MD 21224. EMORY UNIV,ATLANTA,GA 30322. NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 950 EP 950 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000950 ER PT J AU Tomita, H Egashira, K Usui, M Takeya, M Yoshimura, T AF Tomita, H Egashira, K Usui, M Takeya, M Yoshimura, T TI Angiotensin type 1 receptor antagonist prevents vascular monocyte infiltration and monocyte chemoattractant proten-1 expression in the rat heart induced by chronic inhibition of nitric oxide synthesis SO CIRCULATION LA English DT Meeting Abstract C1 KYUSHU UNIV,FUKUOKA 812,JAPAN. KUMAMOTO UNIV,KUMAMOTO,JAPAN. NCI,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 975 EP 975 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000969 ER PT J AU Koh, KK Bui, MN Mincemoyer, R Cannon, RO AF Koh, KK Bui, MN Mincemoyer, R Cannon, RO TI The effect of hormone therapy on inflammatory cell adhesion molecules in postmenopausal women SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 978 EP 978 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88000978 ER PT J AU Arai, AE Epstein, FH Bove, KE Wolff, SD AF Arai, AE Epstein, FH Bove, KE Wolff, SD TI Aortic valve leaflet visualization with black blood MRI SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. GE CO,MED SYST,MILWAUKEE,WI 53201. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 1053 EP 1053 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88001051 ER PT J AU Cross, HR Lu, LY Steenbergen, C Philipson, KD Murphy, E AF Cross, HR Lu, LY Steenbergen, C Philipson, KD Murphy, E TI Transgenic mice overexpressing the Na/Ca exchanger exhibit a sex specific increase in susceptibility to ischemic injury SO CIRCULATION LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. DUKE UNIV,DURHAM,NC. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 1107 EP 1107 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88001105 ER PT J AU Harada, K Jones, M Yamada, I AF Harada, K Jones, M Yamada, I TI Effect of aortic regurgitant volume on left ventricular performance: A chronic animal model study SO CIRCULATION LA English DT Meeting Abstract C1 OREGON HLTH SCI UNIV,PORTLAND,OR 97201. NHLBI,LAMS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 1135 EP 1135 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88001133 ER PT J AU Singh, JP Larson, MG Manolio, TA Lauer, MS AF Singh, JP Larson, MG Manolio, TA Lauer, MS TI Blood pressure response during treadmill testing as a risk factor for the development of hypertension SO CIRCULATION LA English DT Meeting Abstract C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA. NIH,BETHESDA,MD 20892. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. RI Lauer, Michael/L-9656-2013 OI Lauer, Michael/0000-0002-9217-8177 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 1236 EP 1236 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88001234 ER PT J AU Schreiner, PJ Lewis, CE Folsom, AR Liu, K Sholinsky, P Jacobs, DR AF Schreiner, PJ Lewis, CE Folsom, AR Liu, K Sholinsky, P Jacobs, DR TI Waist circumference change predicts 10-year change in triglycerides: The CARDIA study SO CIRCULATION LA English DT Meeting Abstract C1 UNIV MINNESOTA,MINNEAPOLIS,MN 55455. UNIV ALABAMA,TUSCALOOSA,AL 35487. NORTHWESTERN UNIV,CHICAGO,IL 60611. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 1239 EP 1239 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88001237 ER PT J AU Sakai, N Vaisman, BL Koch, CA Paiz, JA Brewer, HB SantamarinaFojo, S Paigen, B AF Sakai, N Vaisman, BL Koch, CA Paiz, JA Brewer, HB SantamarinaFojo, S Paigen, B TI Analysis of aortic atherosclerosis and glomerulosclerosis in LCAT knockout mice SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. JACKSON LAB,BAR HARBOR,ME 04609. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 1258 EP 1258 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88001267 ER PT J AU Brousseau, ME Phair, RD Wang, J Vaisman, BL Talley, GD SantamarinaFojo, S Brewer, HB Hoeg, JM AF Brousseau, ME Phair, RD Wang, J Vaisman, BL Talley, GD SantamarinaFojo, S Brewer, HB Hoeg, JM TI Overexpression of LCAT in transgenic rabbits enhances LDL catabolism via the LDL receptor pathway SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. BIOINFORMAT SERV,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 1262 EP 1262 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88001271 ER PT J AU Prasad, A Padder, F Andrews, NP Husain, S Mincemoyer, R Panza, JA Quyyumi, AA AF Prasad, A Padder, F Andrews, NP Husain, S Mincemoyer, R Panza, JA Quyyumi, AA TI Glutathione and N-acetylcysteine improve endothelial dysfunction in humans SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 1391 EP 1391 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88001389 ER PT J AU Cardillo, C Kilcoyne, CM Quyyumi, AA Cannon, RO Panza, JA AF Cardillo, C Kilcoyne, CM Quyyumi, AA Cannon, RO Panza, JA TI Increased activity of endogenous endothelin in hypercholesterolemic patients SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 1395 EP 1395 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88001393 ER PT J AU Heldman, AW Cheng, L Heller, P Jenkins, M Ware, M Nater, C Rezai, B Hruban, RH Sollott, SJ Kinsella, J Lakatta, EG Brinker, JA Froehlich, J AF Heldman, AW Cheng, L Heller, P Jenkins, M Ware, M Nater, C Rezai, B Hruban, RH Sollott, SJ Kinsella, J Lakatta, EG Brinker, JA Froehlich, J TI Paclitaxel applied directly to stents inhibits neointimal growth without thrombotic complications in a porcine coronary artery model of restenosis SO CIRCULATION LA English DT Meeting Abstract C1 JOHNS HOPKINS,BALTIMORE,MD. NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. RI Heldman, Alan/K-8784-2012 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 1602 EP 1602 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88001598 ER PT J AU Shirani, J Lee, J Srinivasan, G Kitsiou, AN Quigg, RJ Pick, R Bacharach, SL Ohler, L Davis, CM Dilsizian, V AF Shirani, J Lee, J Srinivasan, G Kitsiou, AN Quigg, RJ Pick, R Bacharach, SL Ohler, L Davis, CM Dilsizian, V TI Relation between the severity of reduction in thallium activity within irreversible defects and percent collagen replacement in chronic ischemic cardiomyopathy SO CIRCULATION LA English DT Meeting Abstract C1 ALBERT EINSTEIN COLL MED,BRONX,NY 10467. NHLBI,BETHESDA,MD 20892. NORTHWESTERN UNIV,CHICAGO,IL 60611. COLOMBIA MICHAEL REESE HOSP,CHICAGO,IL. NIH,BETHESDA,MD 20892. FAIRFAX HOSP,FAIRFAX,VA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 1722 EP 1722 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88001715 ER PT J AU Prasad, A Mincemoyer, R Hathaway, L Panza, JA Quyyumi, AA AF Prasad, A Mincemoyer, R Hathaway, L Panza, JA Quyyumi, AA TI Angiotensin converting enzyme inhibition increases nitric oxide bioavailability in the atherosclerotic human coronary circulation SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 1758 EP 1758 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88001750 ER PT J AU Shiota, T Jones, M Ota, T Chikada, M Fleishman, CE Kisslo, J Cotter, B Ryan, TJ Demaria, AN vonRamm, OT Sahn, DJ AF Shiota, T Jones, M Ota, T Chikada, M Fleishman, CE Kisslo, J Cotter, B Ryan, TJ Demaria, AN vonRamm, OT Sahn, DJ TI Application of a new real-time three-dimensional method for evaluating right ventricular stroke volume SO CIRCULATION LA English DT Meeting Abstract C1 OREGON HLTH SCI UNIV,PORTLAND,OR 97201. NHLBI,LAMS,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DURHAM,NC. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 1830 EP 1830 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88001821 ER PT J AU Ota, T Jones, M Fleishman, CE Shiota, T Zetta, AD Cotter, B Demaria, AN Sahn, DJ Ryan, TJ vonRamm, OT Kisslo, J AF Ota, T Jones, M Fleishman, CE Shiota, T Zetta, AD Cotter, B Demaria, AN Sahn, DJ Ryan, TJ vonRamm, OT Kisslo, J TI Accuracy of left ventricular stroke volume measurement using real-time, three dimensional echocardiography and electromagnetic flow probe in vivo SO CIRCULATION LA English DT Meeting Abstract C1 DUKE UNIV,MED CTR,DURHAM,NC. NHLBI,LAMS,BETHESDA,MD 20892. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 1831 EP 1831 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88001822 ER PT J AU Beckman, KJ Klein, RC Page, RL Love, JC Follmann, D Moore, RT Kandrac, J Cannom, DS Duff, HJ Hallstrom, A AF Beckman, KJ Klein, RC Page, RL Love, JC Follmann, D Moore, RT Kandrac, J Cannom, DS Duff, HJ Hallstrom, A TI Effect of antiarrhythmic therapy on survival in patients with ventricular tachycardia or fibrillation in the antiarrhythmics vs implantable defibrillators (AVID)trial registry SO CIRCULATION LA English DT Meeting Abstract C1 UNIV OKLAHOMA,OKLAHOMA CITY,OK. UNIV UTAH,SALT LAKE CITY,UT. UNIV TEXAS,DALLAS,TX 75230. MAINE MED CTR,PORTLAND,ME 04102. NHLBI,BETHESDA,MD 20892. UNIV WASHINGTON,SEATTLE,WA 98195. CASE WESTERN RESERVE UNIV,UNIV HOSP CLEVELAND,CLEVELAND,OH 44106. GOOD SAMARITAN HOSP,LOS ANGELES,CA. UNIV CALGARY,CALGARY,AB,CANADA. RI Page, Richard/L-5501-2014 OI Page, Richard/0000-0001-5603-1330 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 1868 EP 1868 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88001859 ER PT J AU Austin, MA Rodriguez, BL McKnight, B Curb, JD Sharp, DS AF Austin, MA Rodriguez, BL McKnight, B Curb, JD Sharp, DS TI Low-density lipoprotein (LDL) particle size and plasma triglyceride (TG) as predictors of coronary heart disease (CHD) in older Japanese American men SO CIRCULATION LA English DT Meeting Abstract C1 UNIV HAWAII,HONOLULU,HI 96822. UNIV WASHINGTON,SEATTLE,WA 98195. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 1877 EP 1877 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88001874 ER PT J AU Fox, NL Czajkowski, S Dupuis, GH Herd, JA Hoogwerf, B Lindquist, R Terrin, ML AF Fox, NL Czajkowski, S Dupuis, GH Herd, JA Hoogwerf, B Lindquist, R Terrin, ML TI Quality of life in POST CABG patients SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. MONTREAL HEART INST,MONTREAL,PQ H1T 1C8,CANADA. BAYLOR COLL MED,HOUSTON,TX 77030. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. MINNEAPOLIS HEART INST FDN,MINNEAPOLIS,MN. MARYLAND MED RES INST,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 1904 EP 1904 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88001895 ER PT J AU Rywik, TM Blackman, MR Zink, RC Vaitkevicius, PV Yataco, AR Stewart, KJ Cottrell, EH Wright, JG Katzel, LI Fleg, JL AF Rywik, TM Blackman, MR Zink, RC Vaitkevicius, PV Yataco, AR Stewart, KJ Cottrell, EH Wright, JG Katzel, LI Fleg, JL TI Can endurance training enhance endothelial function in older men? SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. JOHNS HOPKINS BAYVIEW MED CTR,BALTIMORE,MD. VET ADM MED CTR,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 1979 EP 1979 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88001970 ER PT J AU Rubanyi, GM Johnson, BD Zheng, W Korach, KS Sheuer, T Catterall, WA AF Rubanyi, GM Johnson, BD Zheng, W Korach, KS Sheuer, T Catterall, WA TI Prolongation of action potential duration and increased expression of L-type Ca2+-channels in cardiac myocytes of estrogen receptor knock-out (ERKO) mice SO CIRCULATION LA English DT Meeting Abstract C1 BERLEX BIOSCI,RICHMOND,CA. UNIV WASHINGTON,SEATTLE,WA 98195. NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 1994 EP 1994 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88001985 ER PT J AU Juhasz, O Hiraoka, H Cheng, L Schmidt, AM Stern, DM Crow, MT AF Juhasz, O Hiraoka, H Cheng, L Schmidt, AM Stern, DM Crow, MT TI The stimulation of monocyte chemoattractant protein-1 expression by advanced glycation endproducts requires the cytosolic domain of the 35-50 Kd receptor, RAGE SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. COLUMBIA UNIV,NEW YORK,NY. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 2030 EP 2030 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88002021 ER PT J AU Hunninghake, D Knatterud, G Campeau, L WHite, CW Domanski, MJ Forrester, JS Gobel, F Geller, N Herd, JA Hoogwerf, B Rosenberg, Y AF Hunninghake, D Knatterud, G Campeau, L WHite, CW Domanski, MJ Forrester, JS Gobel, F Geller, N Herd, JA Hoogwerf, B Rosenberg, Y TI Baseline HDL-cholesterol and triglycerides as predictors of progression of atherosclerosis in saphenous vein grafts: NHLBI post-CABG clinical trial SO CIRCULATION LA English DT Meeting Abstract C1 UNIV MINNESOTA,MINNEAPOLIS,MN. MARYLAND MED RES INST,BALTIMORE,MD. MONTREAL HEART INST,MONTREAL,PQ H1T 1C8,CANADA. NHLBI,BETHESDA,MD 20892. CEDARS SINAI MED CTR,LOS ANGELES,CA 90048. MINNEAPOLIS HEART INST FDN,MINNEAPOLIS,MN. BAYLOR COLL MED,HOUSTON,TX 77030. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 2306 EP 2306 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88002294 ER PT J AU Bruce, C Sharp, DS Tall, AR AF Bruce, C Sharp, DS Tall, AR TI High HDL and increased coronary heart disease in hypertriglyceridemic men with the 405V polymorphism in the cholesteryl ester transfer protein SO CIRCULATION LA English DT Meeting Abstract C1 COLUMBIA UNIV,NEW YORK,NY. NHLBI,HONOLULU,HI. RI Bruce, Can/A-6949-2015 OI Bruce, Can/0000-0002-3101-1250 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 2307 EP 2307 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88002295 ER PT J AU Hoogwerf, B Hunninghake, D Campeau, L Herd, A Hickey, A Canner, J Geller, N White, CW AF Hoogwerf, B Hunninghake, D Campeau, L Herd, A Hickey, A Canner, J Geller, N White, CW TI LDL cholesterol lowering shows angiographic and clinical benefit in diabetic patients in the Post CABG trial SO CIRCULATION LA English DT Meeting Abstract C1 CLEVELAND CLIN FDN,CLEVELAND,OH 44195. UNIV MINNESOTA,MINNEAPOLIS,MN. MONTREAL HEART INST,MONTREAL,PQ H1T 1C8,CANADA. BAYLOR COLL MED,HOUSTON,TX 77030. CEDARS SINAI MED CTR,LOS ANGELES,CA 90048. MARYLAND MED RES INST,BALTIMORE,MD. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 2313 EP 2313 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88002301 ER PT J AU Hunt, SC Cook, NR Oberman, A Cutler, JA Hennekens, CH Allender, PS Walker, WG Whelton, PK Williams, RR AF Hunt, SC Cook, NR Oberman, A Cutler, JA Hennekens, CH Allender, PS Walker, WG Whelton, PK Williams, RR TI Is hypertension prevention by sodium reduction related to angiotensinogen genotype? The trials of hypertension prevention study, phase II SO CIRCULATION LA English DT Meeting Abstract C1 UNIV UTAH,SALT LAKE CITY,UT. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV ALABAMA,BIRMINGHAM,AL. NHLBI,BETHESDA,MD 20892. JOHNS HOPKINS,BALTIMORE,MD. TULANE UNIV,NEW ORLEANS,LA 70118. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 2443 EP 2443 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88002430 ER PT J AU Jenkins, LS Steinberg, JS Kutalek, SP Cook, JR Schron, EB Friedman, PL Cross, J BosworthFarrel, S Roth, J Yao, Q AF Jenkins, LS Steinberg, JS Kutalek, SP Cook, JR Schron, EB Friedman, PL Cross, J BosworthFarrel, S Roth, J Yao, Q TI Quality of life in patients enrolled in the antiarrhythmics versus implantable defibrillators(AVID)Trial SO CIRCULATION LA English DT Meeting Abstract C1 UNIV MARYLAND,BALTIMORE,MD 21201. ST LUKES ROOSEVELT HOSP,NEW YORK,NY. ALLEGHENY UNIV,PHILADELPHIA,PA. BAYSTATE MED CTR,SPRINGFIELD,MA. NATL INST HLTH,BETHESDA,MD. HARVARD UNIV,BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. MAINE MED CTR,PORTLAND,ME 04102. MED COLL WISCONSIN,MILWAUKEE,WI 53226. WASHINGTON UNIV,SEATTLE,WA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 2451 EP 2451 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88002439 ER PT J AU Kuschel, M Spurgeon, HA Karczewski, P Lakatta, EG Krause, EG Xiao, RP AF Kuschel, M Spurgeon, HA Karczewski, P Lakatta, EG Krause, EG Xiao, RP TI Lack of protein kinase activation and protein phosphorylation during cardiac beta(2)-adrenergic receptor stimulation in the intact dog SO CIRCULATION LA English DT Meeting Abstract C1 MAX DELBRUCK CTR MOL MED,BERLIN,GERMANY. NIH,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 2 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 2485 EP 2485 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88002472 ER PT J AU Gaziano, JM Hennekens, CH ODonnell, CJ Breslow, JL Buring, JE AF Gaziano, JM Hennekens, CH ODonnell, CJ Breslow, JL Buring, JE TI Fasting triglycerides, high-density lipoprotein, and risk of myocardial infarction SO CIRCULATION LA English DT Article DE triglycerides; lipoproteins; infarction; coronary disease ID CORONARY HEART-DISEASE; PLASMA TRIGLYCERIDE; RICH LIPOPROTEINS; CHOLESTEROL; QUESTIONNAIRE; PROGRESSION; PREVALENCE; FRAMINGHAM; MORTALITY AB Background Recent data suggest that triglyceride-rich lipoproteins may play a role in atherogenesis. However, whether triglycerides, as a marker for these lipoproteins, represent an independent risk factor for coronary heart disease remains unclear, despite extensive research. Several methodological issues have limited the interpretability of the existing data. Methods and Results We examined the interrelationships of fasting triglycerides, other lipid parameters, and nonlipid risk factors with risk of myocardial infarction among 340 cases and an equal number of age-, sex-, and community-matched control subjects. Cases were men or women of <76 years of age with no prior history of coronary disease who were discharged from one of six Boston area hospitals with the diagnosis of a confirmed myocardial infarction. In crude analyses, we observed a significant association of elevated fasting triglycerides with risk of myocardial infarction (relative risk [RR] in the highest compared with the lowest quartile=6.8; 95% confidence interval [CI]=3.8 to 12.1; P for trend <.001). Results were not materially altered after control for nonlipid coronary risk factors. As expected, the relationship was attenuated after adjustment for HDL but remained statistically significant (RR in the highest quartile=2.7; 95% confidence interval [CI]=1.4 to 5.5; P for trend=.016). Furthermore, the ratio of triglycerides to HDL was a strong predictor of myocardial infarction (RR in the highest compared with the lowest quartile=16.0; 95% CI=7.7 to 33.1; P for trend <.001). Conclusions Our data indicate that fasting triglycerides, as a marker for triglyceride-rich lipoproteins, may provide valuable information about the atherogenic potential of the lipoprotein profile, particularly when considered in context of HDL levels. C1 BRIGHAM & WOMENS HOSP,DEPT MED,DIV CARDIOVASC,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT AMBULATORY CARE & PREVENT,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. HARVARD UNIV,VET AFFAIRS MED CTR,DEPT MED,BROCKTON,MA 02401. ROCKEFELLER UNIV,LAB BIOCHEM GENET & METAB,NEW YORK,NY. FRAMINGHAM HEART DIS EPIDEMIOL STUDY,NHLBI,FRAMINGHAM,MA. RP Gaziano, JM (reprint author), BRIGHAM & WOMENS HOSP,DEPT MED,DIV PREVENT MED,900 COMMONWEALTH AVE E,BOSTON,MA 02215, USA. RI Breslow, Jan/B-7544-2008 FU NHLBI NIH HHS [HL-07575, HL-21006, HL-24423] NR 32 TC 264 Z9 279 U1 1 U2 4 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 BP 2520 EP 2525 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC671 UT WOS:A1997YC67100012 PM 9355888 ER PT J AU Kwiterovich, PO Barton, BA McMahon, RP Obarzanek, E Hunsberger, S SimonsMorton, D Kimm, SYS Friedman, LA Lasser, N Robson, A Lauer, R Stevens, V VanHorn, L Gidding, S Snetselaar, L Hartmuller, VW Greenlick, M Franklin, F AF Kwiterovich, PO Barton, BA McMahon, RP Obarzanek, E Hunsberger, S SimonsMorton, D Kimm, SYS Friedman, LA Lasser, N Robson, A Lauer, R Stevens, V VanHorn, L Gidding, S Snetselaar, L Hartmuller, VW Greenlick, M Franklin, F TI Effects of diet and sexual maturation on low-density lipoprotein cholesterol during puberty - The Dietary Intervention Study in Children (DISC) SO CIRCULATION LA English DT Article DE coronary disease; pediatrics; diet; hyperlipoproteinemia; lipoproteins ID SERUM-LIPIDS; YOUNG-ADULTS; AGE; TRACKING; HEALTH; RISK; REGRESSION; CHILDHOOD; OBESITY; PLASMA AB Background The Dietary Intervention Study in Children (DISC) is a multicenter, randomized, controlled clinical trial designed to examine the efficacy and safety of a dietary intervention to reduce serum LDL cholesterol (LDL-C) in children with elevated LDL-C. Methods and Results The effects of dietary intake of fat and cholesterol and of sexual maturation and body mass index (BMI) on LDL-C were examined in a 3-year longitudinal study of 663 boys and girls (age 8 to 10 years at baseline) with elevated LDL-C levels. Multiple linear regression was used to predict LDL-C at 3 years. For boys, LDL-C decreased by 0.018 mmol/L for each 10 mg/4.2 MJ decrease in dietary cholesterol (P<.05). For girls, no single nutrient was significant in the model, but a treatment group effect was evident (P<.05). In both sexes, BMI at 3 years and LDL-C at baseline were significant and positive predictors of LDL-C levels. In boys, the average LDL-C level was 0.603 mmol/L lower at Tanner stage 4+ than at Tanner stage 1 (P<.01). In girls, the average LDL-C level was 0.274 mmol/L lower at Tanner stage 4+ than at Tanner stage 1 (P<.05). Conclusions In pubertal children, sexual maturation, BMI, dietary intervention (in girls), and dietary cholesterol (in boys) were significant in determining LDL-C. Sexual maturation was the factor associated with the greatest difference in LDL-C. Clinicians screening for dyslipidemia or following dyslipidemic children should be aware of the powerful effects of pubertal change on measurements of lipoproteins. C1 MARYLAND MED RES INST,BALTIMORE,MD 21210. JOHNS HOPKINS UNIV,BALTIMORE,MD. NHLBI,NIH,BETHESDA,MD 20892. UNIV PITTSBURGH,PITTSBURGH,PA 15260. UNIV MED & DENT NEW JERSEY,NEWARK,NJ 07103. CHILDRENS HOSP,NEW ORLEANS,LA. UNIV IOWA,IOWA CITY,IA 52242. KAISER PERMANENTE CTR HLTH RES,PORTLAND,OR. NORTHWESTERN UNIV,CHICAGO,IL 60611. CHILDRENS HOSP,CHICAGO,IL. NCI,ROCKVILLE,MD. UNIV ALABAMA,BIRMINGHAM,AL. RI McMahon, Robert/C-5462-2009; OI Barton, Bruce/0000-0001-7878-8895 FU NHLBI NIH HHS [U01-HL-37947, U01-HL-37948, U01-HL-37954] NR 34 TC 52 Z9 57 U1 1 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 BP 2526 EP 2533 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC671 UT WOS:A1997YC67100013 PM 9355889 ER PT J AU Jacobs, AK Bourassa, MG Kip, KE Sopko, G Jones, RH Roubin, GS Alderman, EL Feit, F Detre, KA AF Jacobs, AK Bourassa, MG Kip, KE Sopko, G Jones, RH Roubin, GS Alderman, EL Feit, F Detre, KA TI Is intended incomplete revascularization an acceptable strategy? The bypass angioplasty revascularization investigation (BARI) SO CIRCULATION LA English DT Meeting Abstract C1 BOSTON MED CTR,BOSTON,MA. MONTREAL HEART INST,MONTREAL,PQ H1T 1C8,CANADA. UNIV PITTSBURGH,PITTSBURGH,PA. NIH,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DURHAM,NC. UNIV ALABAMA,BIRMINGHAM,AL. STANFORD UNIV,STANFORD,CA 94305. NYU,NEW YORK,NY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 2542 EP 2542 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88002528 ER PT J AU Jacobs, AK Bourassa, MG Kip, KE Sopko, G Rosen, AD Chaitman, BR Schwartz, L Whitlow, PI Sharaf, BL Kellett, MA Shemin, RJ AF Jacobs, AK Bourassa, MG Kip, KE Sopko, G Rosen, AD Chaitman, BR Schwartz, L Whitlow, PI Sharaf, BL Kellett, MA Shemin, RJ TI Incomplete revascularization via PTCA vs CABG: The bypass angioplasty revascularization investigation (BARI) SO CIRCULATION LA English DT Meeting Abstract C1 BOSTON MED CTR,BOSTON,MA. MONTREAL HEART INST,MONTREAL,PQ H1T 1C8,CANADA. UNIV PITTSBURGH,PITTSBURGH,PA. NIH,BETHESDA,MD 20892. ST LOUIS UNIV,ST LOUIS,MO 63103. TORONTO HOSP,TORONTO,ON M5T 2S8,CANADA. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. RHODE ISL HOSP,PROVIDENCE,RI. MAINE MED CTR,PORTLAND,ME 04102. BOSTON UNIV,BOSTON,MA 02215. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 2548 EP 2548 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88002534 ER PT J AU Chaitman, BR Hardison, RM Rosen, AD Abhayakumar, A Stocke, K Bourassa, MG Rautaharju, PM Sopko, G Detre, KA AF Chaitman, BR Hardison, RM Rosen, AD Abhayakumar, A Stocke, K Bourassa, MG Rautaharju, PM Sopko, G Detre, KA TI Differential prognostic impact of baseline ECG abnormalities after coronary revascularization in the BARI trial SO CIRCULATION LA English DT Meeting Abstract C1 ST LOUIS UNIV,ST LOUIS,MO 63103. UNIV PITTSBURGH,PITTSBURGH,PA. MONTREAL HEART INST,MONTREAL,PQ H1T 1C8,CANADA. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 2563 EP 2563 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88002549 ER PT J AU Rywik, TM Zink, RC Khan, AA OConnor, FC Gittings, NS Wright, JG Fleg, JL AF Rywik, TM Zink, RC Khan, AA OConnor, FC Gittings, NS Wright, JG Fleg, JL TI Prediction of future coronary events in asymptomatic subjects with positive exercise ECG SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 2576 EP 2576 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88002562 ER PT J AU Rywik, TM Zink, RC Gittings, NS Wright, JG Khan, AA Fleg, JL AF Rywik, TM Zink, RC Gittings, NS Wright, JG Khan, AA Fleg, JL TI Do intermediate exercise ECG abnormalities predict future coronary events in asymptomatic volunteers? SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 2580 EP 2580 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88002566 ER PT J AU Li, ZH Nater, C AF Li, ZH Nater, C TI Localized apoptosis and enhanced expression of p53 and interleukin-1 beta converting enzyme (ICE) proteins in human aortic atherosclerotic lesions SO CIRCULATION LA English DT Meeting Abstract C1 NIA,BALTIMORE,MD 21224. JOHNS HOPKINS,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 2716 EP 2716 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88002701 ER PT J AU Quyyumi, A AF Quyyumi, A TI Contribution of nitric oxide to metabolic coronary vasodilation in the human heart - Response SO CIRCULATION LA English DT Letter RP Quyyumi, A (reprint author), NHLBI,CARDIOL BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 BP 2736 EP 2736 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC671 UT WOS:A1997YC67100048 ER PT J AU Tomita, H Egashira, K Inoue, MK Takeya, M Yoshimura, T Takeshita, A AF Tomita, H Egashira, K Inoue, MK Takeya, M Yoshimura, T Takeshita, A TI Chronic inhibition of nitric oxide synthesis induces monocyte macrophage infiltration and myofibroblast formation in the rat heart SO CIRCULATION LA English DT Meeting Abstract C1 KYUSHU UNIV,FUKUOKA 812,JAPAN. KUMAMOTO UNIV,KUMAMOTO,JAPAN. NATL CANC INST,FREDERICK,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 2754 EP 2754 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88002735 ER PT J AU Hilbert, SL Luna, RE Zhang, J Wang, YN Hopkins, RA Yu, ZX Ferrans, VJ AF Hilbert, SL Luna, RE Zhang, J Wang, YN Hopkins, RA Yu, ZX Ferrans, VJ TI Allograft heart valves: Assessment of cell viability by confocal microscopy. SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. US FDA,LAUREL,MD. GEORGETOWN UNIV,WASHINGTON,DC 20057. US FDA,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 2846 EP 2846 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88002828 ER PT J AU Li, XK Delabays, A Yamada, I AF Li, XK Delabays, A Yamada, I TI Three-dimensional ultrasound reconstruction of the left ventricle for assessing ventricular function in aortic regurgitation: A chronic animal model study SO CIRCULATION LA English DT Meeting Abstract C1 OREGON HLTH SCI UNIV,PORTLAND,OR 97201. TUFTS NEW ENGLAND MED CTR,BOSTON,MA. NHLBI,LAMS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 3030 EP 3030 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88003011 ER PT J AU Long, XL Lakatta, EG ONeil, L Boluyt, MO Seth, P Crow, MT AF Long, XL Lakatta, EG ONeil, L Boluyt, MO Seth, P Crow, MT TI Cardiomyocyte apoptosis triggered by the cyclin kinase inhibitor, p21/waf1, is suppressed by the adrenergic agonist, phenylephrine SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. NIH,BETHESDA,MD 20892. NIA,GERONTOL RES CTR,LCS,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 3096 EP 3096 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88003077 ER PT J AU Tanaka, K Johnson, TM Finkel, T Sandford, G Epstein, SE AF Tanaka, K Johnson, TM Finkel, T Sandford, G Epstein, SE TI Effect of human cytomegalovirus immediate early proteins on p53-dependent and p53-independent pathways mediating apoptosis in coronary artery smooth muscle cells SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. MED COLL WISCONSIN,MILWAUKEE,WI 53226. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 3131 EP 3131 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88003112 ER PT J AU Merz, CNB Kelsey, SF Pepine, CJ Reichek, N Reis, SE Rogers, WJ Sharaf, BL Sopko, G AF Merz, CNB Kelsey, SF Pepine, CJ Reichek, N Reis, SE Rogers, WJ Sharaf, BL Sopko, G TI Women's ischemic syndrome evaluation (WISE): Initial report from pilot phase SO CIRCULATION LA English DT Meeting Abstract C1 CEDARS SINAI MED CTR,LOS ANGELES,CA 90048. UNIV PITTSBURGH,PITTSBURGH,PA. UNIV FLORIDA,GAINESVILLE,FL. ALLEGHENY UNIV HLTH SCI,PITTSBURGH,PA. BROWN UNIV,PROVIDENCE,RI 02912. NIH,BETHESDA,MD 20892. RI Reis, Steven/J-3957-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 3151 EP 3151 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88003132 ER PT J AU Farb, A Heller, PF Carter, AJ Cheng, L Min, DH Kolodgie, F Froehlich, JP Virmani, R AF Farb, A Heller, PF Carter, AJ Cheng, L Min, DH Kolodgie, F Froehlich, JP Virmani, R TI Paclitaxel polymer-coated stents reduce neointima SO CIRCULATION LA English DT Meeting Abstract C1 ARMED FORCES INST PATHOL,WASHINGTON,DC 20306. NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD. NIA,CARDIOVASC SCI LAB,NIH,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 3394 EP 3394 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88003380 ER PT J AU Korzick, DH Boluyt, MO Lakatta, EG AF Korzick, DH Boluyt, MO Lakatta, EG TI Diminished PKC but preserved non-PKC components of the alpha(1)-adrenergic contractile response in hearts of aging rats SO CIRCULATION LA English DT Meeting Abstract C1 NIA,LCS,CTR GERONTOL RES,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 3423 EP 3423 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88003408 ER PT J AU Zhang, SJ Xiao, RP Lakatta, EG Cheng, HP AF Zhang, SJ Xiao, RP Lakatta, EG Cheng, HP TI Is the current ''two-state'' model adequate to explain receptor-G protein coupling? SO CIRCULATION LA English DT Meeting Abstract C1 NIA,LCS,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 2 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 3428 EP 3428 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88003413 ER PT J AU Xiao, RP Avdonin, P Zhou, YY Ziman, B Cheng, HP Lakatta, EG AF Xiao, RP Avdonin, P Zhou, YY Ziman, B Cheng, HP Lakatta, EG TI Dual coupling of alpha(2)-adrenoceptors to G(s) and G(i) in murine cardiac cells and its functional significance SO CIRCULATION LA English DT Meeting Abstract C1 NIA,LCS,CTR GERONTOL RES,NIH,BALTIMORE,MD 21224. CARDIOL RES CTR,MOSCOW 121552,RUSSIA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 3429 EP 3429 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88003414 ER PT J AU Srinivasan, G Nour, KA Kitsiou, AN Bacharach, SL Davis, CM Dilsizian, V AF Srinivasan, G Nour, KA Kitsiou, AN Bacharach, SL Davis, CM Dilsizian, V TI Delayed FDG imaging: Differential washout of FDG in ischemic and nonischemic myocardium SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 3499 EP 3499 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88003483 ER PT J AU Chaitman, BR Hardison, RM Rosen, AD Miller, M Dimas, A Bourassa, MG Sopko, G Detre, KA AF Chaitman, BR Hardison, RM Rosen, AD Miller, M Dimas, A Bourassa, MG Sopko, G Detre, KA TI Impact of prior myocardial infarction on 5 year cardiac mortality after coronary angioplasty or bypass surgery in the BARI trial SO CIRCULATION LA English DT Meeting Abstract C1 UNIV PITTSBURGH,PITTSBURGH,PA. ST LOUIS UNIV,ST LOUIS,MO 63103. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. MONTREAL HEART INST,MONTREAL,PQ H1T 1C8,CANADA. NATL INST HLTH,BETHESDA,MD. UNIV PITTSBURGH,PITTSBURGH,PA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 3623 EP 3623 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88003604 ER PT J AU Rodriguez, BL Burchfiel, CM Fujimoto, W Sharp, DS Grove, J Marcovina, SM Abbott, R Curb, JD AF Rodriguez, BL Burchfiel, CM Fujimoto, W Sharp, DS Grove, J Marcovina, SM Abbott, R Curb, JD TI The associations of fasting glucose, insulin and C-peptide with 15-year total mortality; The Honolulu Heart Program SO CIRCULATION LA English DT Meeting Abstract C1 UNIV HAWAII,HONOLULU,HI 96822. HONOLULU HEART PROGRAM,HONOLULU,HI 96822. UNIV WASHINGTON,SEATTLE,WA 98195. NHLBI,HONOLULU,HI. UNIV VIRGINIA,CHARLOTTESVILLE,VA 22903. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 3676 EP 3676 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88003657 ER PT J AU Lewis, CE Williams, OD Bild, DE Kiefe, CI AF Lewis, CE Williams, OD Bild, DE Kiefe, CI TI Maintaining favorable risk factor profiles in young adults: The CARDIA study SO CIRCULATION LA English DT Meeting Abstract C1 UNIV ALABAMA,BIRMINGHAM,AL. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 3677 EP 3677 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88003658 ER PT J AU Hennuyer, NM Peters, JM Staels, B Fievet, C Gonzalez, FJ Auwerx, J AF Hennuyer, NM Peters, JM Staels, B Fievet, C Gonzalez, FJ Auwerx, J TI Role of the peroxisome proliferator activated receptor (PPAR) in HDL metabolism - Insights from studies with PPAR alpha-deficient mice SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. INST PASTEUR,F-59019 LILLE,FRANCE. RI Staels, Bart/N-9497-2016 OI Staels, Bart/0000-0002-3784-1503 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 3697 EP 3697 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88003678 ER PT J AU Cheng, L Mantile, G Pauly, R Monticone, RE Bilato, C Nater, C Crow, MT StetlerStevenson, WG Capogrossi, MC AF Cheng, L Mantile, G Pauly, R Monticone, RE Bilato, C Nater, C Crow, MT StetlerStevenson, WG Capogrossi, MC TI Adenovirus-mediated gene transfer of TIMP-2 inhibits neointimal hyperplasia after balloon injury SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,NIH,LCS,BALTIMORE,MD 21224. JOHNS HOPKINS,BALTIMORE,MD. NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 3743 EP 3743 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88003724 ER PT J AU Aida, S Jones, M Chikada, M Yamada, I Sahn, DJ AF Aida, S Jones, M Chikada, M Yamada, I Sahn, DJ TI Calculation of shunt flow volume through atrial septal defects with digital Doppler color flow mapping method: A chronic animal study SO CIRCULATION LA English DT Meeting Abstract C1 OREGON HLTH SCI UNIV,PORTLAND,OR 97201. NHLBI,LAMS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 3835 EP 3835 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88003814 ER PT J AU Arai, AE Kasserra, CE Gandjbakhche, A Bonner, R Balaban, RS AF Arai, AE Kasserra, CE Gandjbakhche, A Bonner, R Balaban, RS TI Optical reflectance spectroscopy measures cellular oxygenation, in vivo: Effect of work SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. JOHNS HOPKINS,BALTIMORE,MD. RI Bonner, Robert/C-6783-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 3876 EP 3876 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88003852 ER PT J AU Berger, PB Williams, DO Aslanidou, H Kelsey, SF Stadius, M Sopko, G Attubato, M Krone, R AF Berger, PB Williams, DO Aslanidou, H Kelsey, SF Stadius, M Sopko, G Attubato, M Krone, R TI Morphologic features predictive of successful lesion angioplasty: Results of the bypass angioplasty revascularization investigation (BARI) SO CIRCULATION LA English DT Meeting Abstract C1 MAYO CLIN,ROCHESTER,MN. RHODE ISL HOSP,PROVIDENCE,RI. UNIV PITTSBURGH,PITTSBURGH,PA. UNIV WASHINGTON,SEATTLE,WA 98195. NIH,BETHESDA,MD 20892. NYU,NEW YORK,NY. JEWISH HOSP ST LOUIS,ST LOUIS,MO 63110. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 3878 EP 3878 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88003854 ER PT J AU Aida, S Chikada, M AF Aida, S Chikada, M TI Aortic effective regurgitant orifice area computed using a new digital Doppler color flow mapping method SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,LAMS,BETHESDA,MD 20892. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 3915 EP 3915 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88003891 ER PT J AU Afridi, I Panza, JA Zoghbi, WA Oh, JK Marwick, TH AF Afridi, I Panza, JA Zoghbi, WA Oh, JK Marwick, TH TI Dobutamine echocardiography predicts outcome in patients with coronary artery disease and severe ventricular dysfunction SO CIRCULATION LA English DT Meeting Abstract C1 UNIV TEXAS,DALLAS,TX 75230. NIH,BETHESDA,MD 20892. BAYLOR COLL MED,HOUSTON,TX 77030. MAYO CLIN,ROCHESTER,MN. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. RI Marwick, Thomas/C-7261-2013 OI Marwick, Thomas/0000-0001-9065-0899 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 3963 EP 3963 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88003283 ER PT J AU Cooper, HA Dries, DL Domanski, MJ AF Cooper, HA Dries, DL Domanski, MJ TI Diuretics and the risk of arrhythmic death in patients with left ventricular dysfunction SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 3987 EP 3987 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88003955 ER PT J AU Friedman, PL Yao, Q Buxton, AE Engelstein, ED Schron, EB Bishop, V Firth, B Dalamagas, H Flynn, D Torres, VI Coromilas, J AF Friedman, PL Yao, Q Buxton, AE Engelstein, ED Schron, EB Bishop, V Firth, B Dalamagas, H Flynn, D Torres, VI Coromilas, J TI Effect of race on treatment selection in patients with life-threatening ventricular arrhythmia SO CIRCULATION LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. UNIV WASHINGTON,SEATTLE,WA 98195. TEMPLE UNIV,HLTH SCI CTR,PHILADELPHIA,PA 19140. INDIANA UNIV,INDIANAPOLIS,IN 46204. NIH,BETHESDA,MD. LOMA LINDA UNIV,LOMA LINDA,CA 92350. GOOD SAMARITAN HOSP,LOS ANGELES,CA. UNIV ROCHESTER,ROCHESTER,NY. COLUMBIA UNIV,NEW YORK,NY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 4032 EP 4032 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88004000 ER PT J AU Engelstein, ED Friedman, PL Yao, Q Coromilas, J Beckman, KJ Buxton, AE Flynn, D Firth, B Delamagas, H Ledingham, R Schron, EB AF Engelstein, ED Friedman, PL Yao, Q Coromilas, J Beckman, KJ Buxton, AE Flynn, D Firth, B Delamagas, H Ledingham, R Schron, EB TI Gender differences in patients with life-threatening ventricular arrhythmias: Impact on treatment and survival in the antiarrhythmics versus implantable defibrillators (AVID) trial SO CIRCULATION LA English DT Meeting Abstract C1 INDIANA UNIV,INDIANAPOLIS,IN 46204. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. UNIV WASHINGTON,SEATTLE,WA 98195. COLUMBIA UNIV,NEW YORK,NY. UNIV OKLAHOMA,OKLAHOMA CITY,OK. TEMPLE UNIV,HLTH SCI CTR,PHILADELPHIA,PA 19140. UNIV ROCHESTER,ROCHESTER,NY. GOOD SAMARITAN HOSP,LOS ANGELES,CA. UNIV CONNECTICUT,HARTFORD,CT 06112. UNIV WASHINGTON,SEATTLE,WA 98195. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 4036 EP 4036 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88004004 ER PT J AU Hannuksela, ML Meyn, SM Talley, GD Nazih, H Bader, G Shamburek, RD Alaupovic, P Brewer, HB AF Hannuksela, ML Meyn, SM Talley, GD Nazih, H Bader, G Shamburek, RD Alaupovic, P Brewer, HB TI The in vivo metabolism of apolipoprotein E-containing high density lipoproteins SO CIRCULATION LA English DT Meeting Abstract C1 NIH,MDB,NHLBI,BETHESDA,MD 20892. LIPID & LIPOPROT LAB,OKLAHOMA CITY,OK. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 4053 EP 4053 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88004021 ER PT J AU Shamburek, RD Talley, GD Kindt, MR Kuivenhoven, JA Kastelein, JJP Stalenhoef, AFH Brewer, HB AF Shamburek, RD Talley, GD Kindt, MR Kuivenhoven, JA Kastelein, JJP Stalenhoef, AFH Brewer, HB TI Lecithin:Cholesterol acyltransferase deficiency: Human in vivo kinetics of LDL, ApoA-I and ApoA-II in partial LCAT deficiency (fish eye disease) with and without CAD SO CIRCULATION LA English DT Meeting Abstract C1 NIH,MDB,NHLBI,BETHESDA,MD 20892. UNIV AMSTERDAM,AMSTERDAM,NETHERLANDS. UNIV NIJMEGEN HOSP,NL-6500 HB NIJMEGEN,NETHERLANDS. RI Stalenhoef, A.F.H./H-8094-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 4055 EP 4055 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88004023 ER PT J AU Mehran, R Hong, MK Mintz, GS Abizaid, A Dinger, ML Walsh, CL Hoeg, JM AF Mehran, R Hong, MK Mintz, GS Abizaid, A Dinger, ML Walsh, CL Hoeg, JM TI Impaired adaptive arterial remodeling and reduced coronary flow reserve in familial hypercholesterolemia: A combined intravascular ultrasound and physiologic assessment study SO CIRCULATION LA English DT Meeting Abstract C1 ABIZAID WASHINGTON HOSP,WASHINGTON,DC. NIH,BETHESDA,MD 20892. WASHINGTON HOSP,WASHINGTON,DC. NIH,MDB,NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 4057 EP 4057 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88004025 ER PT J AU Riccicni, T Guglielmi, MB Bochner, BS Capogrossi, MC AF Riccicni, T Guglielmi, MB Bochner, BS Capogrossi, MC TI Hypoxia modulates integrin expression in endothelial cells SO CIRCULATION LA English DT Meeting Abstract C1 NIA,BALTIMORE,MD 21224. JOHNS HOPKINS,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 4080 EP 4080 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88004046 ER PT J AU Long, XL Crow, MT Lakatta, EG AF Long, XL Crow, MT Lakatta, EG TI Ice related proteases are involved in hypoxia induced apoptosis in cardiac myocytes SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. NIA,LCS,CTR GERONTOL RES,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 4134 EP 4134 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88004100 ER PT J AU Ferrans, VJ Andrade, ZA Takeda, K Sadigursky, M Ferrans, VJ AF Ferrans, VJ Andrade, ZA Takeda, K Sadigursky, M Ferrans, VJ TI Apoptosis in a canine model of acute chagasic myocarditis SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. FUNDACEO OSWALDO CRUZ,MIN SAUDE,SALVADOR,BA,BRAZIL. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 4151 EP 4151 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88004117 ER PT J AU Cannon, RO Quyyumi, AA Laurienzo, JM Panza, JA AF Cannon, RO Quyyumi, AA Laurienzo, JM Panza, JA TI Does coronary endothelial dysfunction cause myocardial ischemia in syndrome X? SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 1997 VL 96 IS 8 SU S BP 4266 EP 4266 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC880 UT WOS:A1997YC88004231 ER PT J AU Yu, CL Driggers, P BarreraHernandez, G Nunez, SB Segars, JH Cheng, SY AF Yu, CL Driggers, P BarreraHernandez, G Nunez, SB Segars, JH Cheng, SY TI The tumor suppressor p53 is a negative regulator of estrogen receptor signaling pathways SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HORMONE; GENE AB The estrogen receptor (ER) is a ligand-dependent transcription factor which regulates growth, development, differentiation and reproduction, To test the hypothesis that the diverse effects of the ER could be mediated by interacting with other transcription factors/oncogenes, the present study assessed its interaction with the tumor suppressor p53. p53 is a transcription factor which is involved in cell cycle regulation and apoptosis. We found that the wild-type p53 physically interacted with ER in vivo and repressed the estrogen-activated transcriptional activity. However, p53 mutants had no or reduced repression effect, depending on the sites of mutation. These findings suggest that p53 can cross talk with the ER in hormone-activated signaling pathways in cells. (C) 1997 Academic Press. C1 NCI,MOL BIOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NICHHD,NIH,BETHESDA,MD 20892. NR 15 TC 51 Z9 52 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 OCT 20 PY 1997 VL 239 IS 2 BP 617 EP 620 DI 10.1006/bbrc.1997.7522 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YD849 UT WOS:A1997YD84900046 PM 9344880 ER PT J AU Taira, J Misik, V Riesz, P AF Taira, J Misik, V Riesz, P TI Nitric oxide formation from hydroxylamine by myoglobin and hydrogen peroxide SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE hydroxylamine; nitric oxide; electron spin resonance; spin trapping; hemoprotein; carboxy-PTIO ID ELECTRON-SPIN-RESONANCE; L-ARGININE; GUANYLATE-CYCLASE; FERRYL MYOGLOBIN; HEME-PROTEINS; LINOLEIC-ACID; OXIDATION; INTERMEDIATE; HEMOPROTEINS; METMYOGLOBIN AB Hydroxylamine (HA), which is a natural product of mammalian cells, has been shown to possess vasodilatory properties in several model systems. In this study, HA and methyl-substituted hydroxylamines, N-methylhydroxylamine (NMHA) and N,N-dimethylhydroxylamine (NDMHA), have been tested for their ability to generate free diffusible nitric oxide (NO) in the presence of myoglobin (Mb) and hydrogen peroxide. A NO-specific conversion of 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO) to 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl (carboxy-PTI), measured by electron spin resonance (ESR) spectroscopy, along with nitrite and nitrate production, was observed for HA but not for NMHA and NDMHA. ESR measurements at 77 K showed the formation of the ferrous nitrosyl myoglobin, Mb-NO, in the reaction mixtures containing Mb, H2O2 and HA. Our data also demonstrate that Mb-NO is an end product of the reaction pathway involving Mb, H2O2 and HA, rather than a reaction intermediate in the formation of NO. In summary, our results demonstrate a possible pathway of NO formation from HA, however, the significance of this mechanism for bioactivation of HA in vivo is unknown at the present time. (C) 1997 Elsevier Science B.V. RP Taira, J (reprint author), NCI,RADIAT BIOL BRANCH,NIH,BLDG 10,ROOM B3-B69,BETHESDA,MD 20892, USA. NR 28 TC 26 Z9 30 U1 3 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD OCT 20 PY 1997 VL 1336 IS 3 BP 502 EP 508 DI 10.1016/S0304-4165(97)00064-0 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YC730 UT WOS:A1997YC73000017 PM 9367178 ER PT J AU Potter, K Spencer, RGS McFarland, EW AF Potter, K Spencer, RGS McFarland, EW TI Magnetic resonance microscopy studies of cation diffusion in cartilage (vol 1334, pg 129, 1997) SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Correction, Addition C1 UNIV CALIF SANTA BARBARA,DEPT CHEM ENGN,SANTA BARBARA,CA 93106. NIA,NMR UNIT,NIH,BALTIMORE,MD 21224. RI McFarland, Eric/G-1763-2014 NR 1 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD OCT 20 PY 1997 VL 1336 IS 3 BP 587 EP 587 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YC730 UT WOS:A1997YC73000026 ER PT J AU Specht, JM Wang, G Do, MT Lam, JS Royal, RE Reeves, ME Rosenberg, SA Hwu, P AF Specht, JM Wang, G Do, MT Lam, JS Royal, RE Reeves, ME Rosenberg, SA Hwu, P TI Dendritic cells retrovirally transduced with a model antigen gene are therapeutically effective against established pulmonary metastases SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; COLONY-STIMULATING FACTOR; CYTOTOXIC T-LYMPHOCYTES; LANGERHANS CELLS; MURINE TUMORS; STEM-CELLS; IN-VIVO; IDENTIFICATION; RECOMBINANT; GENERATION AB Dendritic cells (DCs) are bone marrow-derived leukocytes that function as potent antigen presenting cells capable of initiating T cell-dependent responses from quiescent lymphocytes. DC pulsed with tumor-associated antigen (TAA) peptide or protein have recently been demonstrated to elicit antigen-specific protective antitumor immunity in a number of murine models. Transduction of DCs with TAA genes may allow stable, prolonged antigen expression as well as the potential for presentation of multiple, or unidentified, epitopes in association with major histocompatibility complex class I and/or class II molecules. To evaluate the potential efficacy of retrovirally transduced DCs, bone marrow cells harvested from BALB/c mice were transduced with either a model antigen gene encoding beta-galactosidase (beta-gal) or a control gene encoding rat HER-2/neu (Neu) by coculture with irradiated ecotropic retroviral producer lines. Bone marrow cells were differentiated into DC in vitro using granulocyte/macrophage colony-stimulating factor and interleukin-4. After 7 d in culture, cells were 45-78% double positive for DC phenotypic cell surface markers by FACS(C) analysis, and DC transduced with beta-gal were 41-72% positive for beta-gal expression by X-gal staining. In addition, coculture of beta-gal transduced DC with a beta-gal-specific T cell line (CTLx) resulted in the production of large amounts of interferon-gamma, demonstrating that transduced DCs could process and present endogenously expressed beta-gal. DC transduced with beta-gal and control rat HER-2/neu were then used to treat 3-d lung metastases in mice bearing an experimental murine tumor CT26.CL25, expressing the model antigen, beta-gal. Treatment with beta-gal-transduced DC significantly reduced the number of pulmonary metastatic nodules compared with treatment with Hank's balanced salt solution or DCs transduced with rat HER-2/neu. In addition, immunization with beta-gal-transduced DCs resulted in the generation of antigen-specific cytotoxic T lymphocytes (CTLs), which were significantly more reactive against relevant tumor targets than CTLs generated from mice immunized with DCs pulsed with the L-d-restricted beta-gal peptide. The results observed in this rapidly lethal tumor model suggest that DCs transduced with TAA may be a useful treatment modality in tumor immunotherapy. C1 NCI,SURG BRANCH,NIH,BETHESDA,MD 20892. HOWARD HUGHES MED INST,NATL INST HLTH RES SCHOLARS PROGRAM,BETHESDA,MD 20814. OI Specht, Jennifer/0000-0003-1484-2113 NR 31 TC 258 Z9 268 U1 0 U2 4 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 OCT 20 PY 1997 VL 186 IS 8 BP 1213 EP 1221 DI 10.1084/jem.186.8.1213 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA YC950 UT WOS:A1997YC95000005 PM 9334360 ER PT J AU Talanian, RV Yang, XH Turbov, J Seth, P Ghayur, T Casiano, CA Orth, K Froelich, CJ AF Talanian, RV Yang, XH Turbov, J Seth, P Ghayur, T Casiano, CA Orth, K Froelich, CJ TI Granule-mediated killing: Pathways for granzyme B-initiated apoptosis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CELL-DEATH; CONVERTING-ENZYME; KINASE-ACTIVITY; PROTEASE; ACTIVATION; MECHANISM; DELIVERY; LYSIS; CPP32; CRMA AB We report that the serine protease granzyme B (GrB), which is crucial for granule-mediated cell killing, initiates apoptosis in target cells by first maturing caspase-10. In addition, GrB has a limited capacity to mature other caspases and to cause cell death independently of the caspases. Compared with other members, GrB in vitro most efficiently processes caspase-7 and -10. In a human cell model, full maturation of caspase-7 does not occur unless caspase-10 is present. Furthermore, GrB matured caspase-3 with less efficiency than caspase-7 or caspase-10. With the caspases fully inactivated by peptidic inhibitors, GrB induced in Jurkat cells growth arrest and, over a delayed time period, cell death. Thus, the primary mechanism by which GrB initiates cell death is activation of the caspases through caspase-10. However, under circumstances where caspase-10 is absent or dysfunctional, GrB can act through secondary mechanisms including activation of other caspases and direct cell killing by cleavage of noncaspase substrates. The redundant functions of GrB ensure the effectiveness of granule-mediated cell killing, even in target cells that lack the expression or function (e.g., by mutation or a viral serpin) of one or more of the caspases, providing the host with overlapping safeguards against aberrantly replicating, nonself or virally infected cells. C1 NORTHWESTERN UNIV, EVANSTON HOSP, RES DEPT, DEPT MED, EVANSTON, IL 60201 USA. BASF BIORES CORP, WORCESTER, MA 01605 USA. SCRIPPS RES INST, WM KECK AUTOIMMUNE DIS CTR, LA JOLLA, CA 92037 USA. UNIV MICHIGAN, SCH MED, ANN ARBOR, MI 48109 USA. NCI, MED BRANCH, NIH, BETHESDA, MD 20892 USA. RI Yang, Jim/B-3776-2010 FU NCI NIH HHS [F32 CA068769, CA68769] NR 39 TC 143 Z9 144 U1 1 U2 3 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 OCT 20 PY 1997 VL 186 IS 8 BP 1323 EP 1331 DI 10.1084/jem.186.8.1323 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA YC950 UT WOS:A1997YC95000017 PM 9334372 ER PT J AU Kloczkowski, A Jernigan, RL AF Kloczkowski, A Jernigan, RL TI Efficient method to count and generate compact protein lattice conformations SO MACROMOLECULES LA English DT Article ID GLOBULAR-PROTEINS; COPOLYMERS; SEQUENCE; WALKS RP Kloczkowski, A (reprint author), NCI, MOL STRUCT SECT,LAB EXPT & COMPUTAT BIOL,NIH, BLDG 12B, ROOM B116, BETHESDA, MD 20892 USA. RI Jernigan, Robert/A-5421-2012; Kloczkowski, Andrzej/B-9868-2012 NR 17 TC 13 Z9 13 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0024-9297 J9 MACROMOLECULES JI Macromolecules PD OCT 20 PY 1997 VL 30 IS 21 BP 6691 EP 6694 DI 10.1021/ma970662h PG 4 WC Polymer Science SC Polymer Science GA YD345 UT WOS:A1997YD34500046 ER PT J AU Appel, E Kolman, O Kazimirsky, G Blumberg, PM Brodie, C AF Appel, E Kolman, O Kazimirsky, G Blumberg, PM Brodie, C TI Regulation of GDNF expression in cultured astrocytes by inflammatory stimuli SO NEUROREPORT LA English DT Article DE astrocytes; brain inflammation; GDNF; IL-6; LPS; TNF-alpha ID MIDBRAIN DOPAMINERGIC-NEURONS; NEUROTROPHIC FACTOR; MESSENGER-RNA; NERVOUS-SYSTEM; LIPOPOLYSACCHARIDE; BRAIN; RAT; CYTOKINES; PROTEIN; CELLS AB ASTROCYTES express increased levels of neurotrophic factors in response to pathological conditions in the CNS such as injury and inflammation. We have examined the effects of lipopolysaccharide (LPS) and inflammatory cytokines on the expression of GDNF by mouse astrocytes and by C6 glial cells. LPS and tumor necrosis factor-alpha (TNF-alpha) induced an increase in level of glial-derived neurotrophic factor (GDNF) mRNA in both cell types. Similarly, the synthesis of GDNF protein was increased by both treatments. Interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma) induced similar effects on GDNF production, whereas IL-2 and IL-6 had no significant effects. These results indicate that the expression of GDNF in astrocytes is regulated by inflammatory stimuli and therefore may provide neurotrophic support to injured neurons in inflammatory conditions in the CNS. C1 BAR ILAN UNIV,DEPT LIFE SCI,IL-52900 RAMAT GAN,ISRAEL. NCI,MMTP,LCCTP,NIH,BETHESDA,MD 20892. NR 25 TC 90 Z9 93 U1 0 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD OCT 20 PY 1997 VL 8 IS 15 BP 3309 EP 3312 DI 10.1097/00001756-199710200-00023 PG 4 WC Neurosciences SC Neurosciences & Neurology GA YC430 UT WOS:A1997YC43000027 PM 9351662 ER PT J AU Naumann, W Shokhirev, NV Szabo, A AF Naumann, W Shokhirev, NV Szabo, A TI Exact asymptotic relaxation of pseudo-first-order reversible reactions SO PHYSICAL REVIEW LETTERS LA English DT Article ID DIFFUSION-INFLUENCED REACTIONS; LONG-TIME BEHAVIOR; BIMOLECULAR REACTIONS; CHEMICAL-REACTIONS; KINETICS; RECOMBINATION; SIMULATIONS; BINDING; PAIRS AB The relaxation kinetics of the diffusion-influenced reversible reaction A + B C is studied in the pseudo-first-order limit ([B] much greater than [A]) when A and C are static and the B's move independently with diffusion coefficient D. For the initial condition [A(0)] = 1, [C(0)]= 0, it is shown that the asymptotics of [A(t)] for t --> infinity is given in d dimensions by (1 + K-cq[B])(-1) + K-eq(2)[B]/(1 + K-eq[B])(3)f(d)(t) with f(1)(t) = (pi Dt)(-1/2), f(2)(t) = (4 pi Dt)(-1), and f(3)(t) = (4 pi Dt)(-3/2), and where K-eq is the equilibrium constant. By comparing with accurate simulations, this result is found to be exact for d = 1, and we predict that it is exact for higher dimensions. C1 UNIV ARIZONA,DEPT CHEM,TUCSON,AZ 85721. NIDDK,PHYS CHEM LAB,NIH,BETHESDA,MD 20892. RP Naumann, W (reprint author), UNIV LEIPZIG,INST PHYS & THEORET CHEM,D-04318 LEIPZIG,GERMANY. RI Szabo, Attila/H-3867-2012 NR 23 TC 53 Z9 53 U1 0 U2 5 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD OCT 20 PY 1997 VL 79 IS 16 BP 3074 EP 3077 DI 10.1103/PhysRevLett.79.3074 PG 4 WC Physics, Multidisciplinary SC Physics GA YB664 UT WOS:A1997YB66400039 ER PT J AU Stone, DL Biesecker, LG AF Stone, DL Biesecker, LG TI Mitochondrial NP 3243 point mutation is not a common cause of VACTERL association SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Letter ID NP-3243 RP Stone, DL (reprint author), NATL INST HLTH,NATL CTR HUMAN GENOME RES,49 CONVENT DR,BETHESDA,MD 20892, USA. NR 6 TC 6 Z9 6 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 OCT 17 PY 1997 VL 72 IS 2 BP 237 EP 238 DI 10.1002/(SICI)1096-8628(19971017)72:2<237::AID-AJMG20>3.0.CO;2-N PG 2 WC Genetics & Heredity SC Genetics & Heredity GA XY731 UT WOS:A1997XY73100020 PM 9382149 ER PT J AU Nicolaou, KC Vourloumis, D Li, TH Pastor, J Winssinger, N He, Y Ninkovic, S Sarabia, F Vallberg, H Roschangar, F King, NP Finlay, MRV Giannakakou, P VerdierPinard, P Hamel, E AF Nicolaou, KC Vourloumis, D Li, TH Pastor, J Winssinger, N He, Y Ninkovic, S Sarabia, F Vallberg, H Roschangar, F King, NP Finlay, MRV Giannakakou, P VerdierPinard, P Hamel, E TI Designed epothilones: Combinatorial synthesis, tubulin assembly properties, and cytotoxic action against taxol-resistant tumor cells SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH LA English DT Article DE antitumor agents; combinatorial chemistry; epothilones; microreactors; structure-activity relationships ID RING-CLOSING METATHESIS; OLEFIN METATHESIS; ORGANIC-SYNTHESIS; BETA-TUBULIN; BINDING-SITE; AMINO-ACIDS; MICROTUBULE; PHOTOLABELS; MACROLIDES; ASSAY C1 Scripps Res Inst, SKAGGS INST CHEM BIOL, LA JOLLA, CA 92037 USA. UNIV CALIF SAN DIEGO, DEPT CHEM & BIOCHEM, LA JOLLA, CA 92093 USA. NCI, MED BRANCH, DIV CLIN SCI, NIH, BETHESDA, MD 20892 USA. NCI, LAB DRUG DISCOVERY RES & DEV, DEV THERAPEUT PROGRA, DIV CANC TREATMENT DIAG & CTR, FREDERICK, MD 21702 USA. RP Nicolaou, KC (reprint author), Scripps Res Inst, DEPT CHEM, 10550 N TORREY PINES RD, LA JOLLA, CA 92037 USA. RI Li, Tianhu/G-3531-2010; Sarabia, Francisco/M-1845-2014; Pastor, Joaquin/I-4567-2015; Winssinger, Nicolas/B-6710-2017 OI Sarabia, Francisco/0000-0002-5149-3576; Pastor, Joaquin/0000-0003-0553-8021; Winssinger, Nicolas/0000-0003-1636-7766 NR 60 TC 164 Z9 165 U1 1 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 10 11 61, D-69451 WEINHEIM, GERMANY SN 0570-0833 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. Engl. PD OCT 17 PY 1997 VL 36 IS 19 BP 2097 EP 2103 DI 10.1002/anie.199720971 PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA YC826 UT WOS:A1997YC82600016 ER PT J AU Huang, Y Herman, MM Liu, J Katsetos, CD Wills, MR Savory, J AF Huang, Y Herman, MM Liu, J Katsetos, CD Wills, MR Savory, J TI Neurofibrillary lesions in experimental aluminum-induced encephalopathy and Alzheimer's disease share immunoreactivity for amyloid precursor protein, A beta, alpha(1)-antichymotrypsin and ubiquitin-protein conjugates SO BRAIN RESEARCH LA English DT Article DE neurofibrillary degeneration; aluminum; amyloid precursor protein; A beta; alpha(1)-antichymotrypsin; ubiquitin; rabbit ID NEURODEGENERATIVE DISEASES; MONOCLONAL-ANTIBODIES; RABBITS; DEGENERATION; EXPRESSION; ALPHA-1-ANTICHYMOTRYPSIN; DESFERRIOXAMINE; QUANTITATION; ASTROCYTOMAS; DEGRADATION AB Neurofibrillary tangles of Alzheimer's disease contain predominantly tau protein and to a lesser de ee amyloid precursor protein (APP), A beta protein, alpha(1)-antichymotrypsin (ACT) and ubiquitin. Previously we have demonstrated the presence of phosphorylated tau and neurofilament proteins in neurofibrillary degeneration (NFD) induced by aluminum (Al) maltolate in rabbits [Savory et al., Brain Res. 669 (1995) 325-329; Savory et al., Brain Res. 707 (1996) 272-281]. Using the same animal system we have now detected APP, A beta, ACT and ubiquitin-like immunoreactivities in NFD-bearing neurons, often colocalizing in the NFD. Diffuse cytoplasmic staining for APP, A beta and ubiquitin was also present in neurons without NFD from Al maltolate-treated rabbits. This study provides additional support for immunochemical similarities between Al-induced NFD in rabbits and the neurofibrillary tangles in human subjects with Alzheimer's disease. (C) 1997 Elsevier Science B.V. C1 UNIV VIRGINIA,HLTH SCI CTR,DEPT PATHOL,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,HLTH SCI CTR,DEPT INTERNAL MED,CHARLOTTESVILLE,VA 22908. TEMPLE UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19140. NIMH,CLIN BRAIN DISORDERS BRANCH,CTR NEUROSCI,ST ELIZABETHS HOS,IRP,NIH,WASHINGTON,DC 20032. NR 44 TC 39 Z9 40 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 17 PY 1997 VL 771 IS 2 BP 213 EP 220 DI 10.1016/S0006-8993(97)00780-4 PG 8 WC Neurosciences SC Neurosciences & Neurology GA YE999 UT WOS:A1997YE99900005 PM 9401741 ER PT J AU Lim, H Paria, BC Das, SK Dinchuk, JE Langenbach, R Trzaskos, JM Dey, SK AF Lim, H Paria, BC Das, SK Dinchuk, JE Langenbach, R Trzaskos, JM Dey, SK TI Multiple female reproductive failures in cyclooxygenase 2-deficient mice SO CELL LA English DT Article ID DECIDUAL CELL REACTION; MOUSE UTERUS; SELECTIVE-INHIBITION; BLASTOCYST IMPLANTATION; PREOVULATORY FOLLICLES; OVARIAN-STEROIDS; GENE DISRUPTION; H SYNTHASE-1; EXPRESSION; RAT AB Cyclooxygenase (COX) is the rate-limiting enzyme in the synthesis of prostaglandins (PGs) and exists in two isoforms, COX-1 and COX-2. In spite of long-standing speculation, definitive roles of PGs in various events of early pregnancy remain elusive. We demonstrate herein that the targeted disruption of COX-2, but not COX-1, in mice produces multiple failures in female reproductive processes that include ovulation, fertilization, implantation, and decidualization. Using multiple approaches, we conclude that these defects are the direct result of target organ-specific COX-2 deficiency but are not the result of deficiency of pituitary gonadotropins or ovarian steroid hormones, or reduced responsiveness of the target organs to their respective hormones. C1 UNIV KANSAS, MED CTR, DEPT MOL & INTEGRAT PHYSIOL, KANSAS CITY, KS 66160 USA. DUPONT MERCK PHARMACEUT CO, WILMINGTON, DE 19880 USA. NIEHS, LAB EXPT CARCINOGENESIS & MUTAGENESIS, RES TRIANGLE PK, NC 27709 USA. RI Lim, Hyunjung/D-5343-2011 OI Lim, Hyunjung/0000-0003-2191-666X FU NICHD NIH HHS [HD 12304, HD 29968, HD 33994] NR 54 TC 962 Z9 996 U1 6 U2 25 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD OCT 17 PY 1997 VL 91 IS 2 BP 197 EP 208 DI 10.1016/S0092-8674(00)80402-X PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YC350 UT WOS:A1997YC35000007 PM 9346237 ER PT J AU Cerritelli, ME Cheng, NQ Rosenberg, AH McPherson, CE Booy, FP Steven, AC AF Cerritelli, ME Cheng, NQ Rosenberg, AH McPherson, CE Booy, FP Steven, AC TI Encapsidated conformation of bacteriophage T7 DNA SO CELL LA English DT Article ID DOUBLE-STRANDED DNA; CRYO-ELECTRON-MICROSCOPY; HERPES-SIMPLEX VIRUS; X-RAY-DIFFRACTION; 3-DIMENSIONAL STRUCTURE; SECONDARY STRUCTURE; SIMIAN VIRUS-40; WILD-TYPE; HEADS; ORGANIZATION AB The structural organization of encapsidated T7 DNA was investigated by cryo-electron microscopy and image processing. A tail-deletion mutant was found to present two preferred views of phage heads: views along the axis through the capsid vertex where the connector protein resides and via which DNA is packaged; and side views perpendicular to this axis. The resulting images reveal striking patterns of concentric rings in axial views, and punctate arrays in side views. As corroborated by computer modeling, these data establish that the T7 chromosome is spooled around this axis in approximately six coaxial shells in a quasicrystalline packing, possibly guided by the core complex on the inner surface of the connector. C1 NIAMSD,STRUCT BIOL LAB,NIH,BETHESDA,MD 20892. BROOKHAVEN NATL LAB,DEPT BIOL,UPTON,NY 11973. NR 49 TC 252 Z9 256 U1 0 U2 14 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD OCT 17 PY 1997 VL 91 IS 2 BP 271 EP 280 DI 10.1016/S0092-8674(00)80409-2 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YC350 UT WOS:A1997YC35000014 PM 9346244 ER PT J AU Banik, U Wang, GA Wagner, PD Kaufman, S AF Banik, U Wang, GA Wagner, PD Kaufman, S TI Interaction of phosphorylated tryptophan hydroxylase with 14-3-3 proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SURFACE-PLASMON RESONANCE; BIOSPECIFIC INTERACTION ANALYSIS; HIGH-LEVEL EXPRESSION; RAT BRAIN-STEM; TYROSINE-HYDROXYLASE; ACTIVATOR PROTEIN; ESCHERICHIA-COLI; PHENYLALANINE-HYDROXYLASE; CEREBROSPINAL-FLUID; MOLECULAR-CLONING AB Rabbit brain tryptophan hydroxylase (TPH) has been expressed in insect cells (Spodoptera frugiperda) as a histidine-tagged enzyme. The specific activity of the purified fusion enzyme is 80 nmol of 5-hydroxytryptophan/min/mg. Multifunctional regulatory 14-3-3 proteins were purified from fresh bovine brain. Phosphorylation and 14-3-3 proteins play important roles in the regulation of TPH activity. We have found that phosphorylation of TPH by cAMP-dependent protein kinase increased the activity of the hydroxylase by 25-30% and that 14-3-3 proteins increased the hydroxylase activity of phosphorylated TPH by similar to 45%. Under these conditions, the 14-3-3 proteins were not phosphorylated, and unphosphorylated TPH was not activated by 14-3-3 proteins. Surface plasmon resonance analysis demonstrated that 14-3-3 proteins bind to phosphorylated TPH with an affinity constant (K-a) of 4.5 x 10(7) M-1. Binding studies using affinity chromatography also showed that 14-3-3 proteins interact with phosphorylated TPH. The dephosphorylation of TPH by protein phosphatase-l was inhibited by 14-3-3 proteins. Our results demonstrate that 14-3-3 proteins form a complex with phosphorylated brain TPH, thereby increasing its enzymatic activity and inhibiting its dephosphorylation. C1 NCI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. RP Banik, U (reprint author), NIMH,NEUROCHEM LAB,NIH,BLDG 36,RM 3D30,BETHESDA,MD 20892, USA. NR 64 TC 52 Z9 54 U1 1 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 OCT 17 PY 1997 VL 272 IS 42 BP 26219 EP 26225 DI 10.1074/jbc.272.42.26219 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YB139 UT WOS:A1997YB13900024 PM 9334190 ER PT J AU Cupane, A Leone, M Militello, V Friedman, FK Koley, AP Vasquez, GB Brinigar, WS Karavitis, M Fronticelli, C AF Cupane, A Leone, M Militello, V Friedman, FK Koley, AP Vasquez, GB Brinigar, WS Karavitis, M Fronticelli, C TI Modification of beta-chain or beta-chain heme pocket polarity by Val(E11)->Thr substitution has different effects on the steric, dynamic, and functional properties of human recombinant hemoglobin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN DYNAMICS; OPTICAL SPECTROSCOPY; LIGAND-BINDING; ABSORPTION-SPECTROSCOPY; TEMPERATURE-DEPENDENCE; NEUTRON-SCATTERING; ESCHERICHIA-COLI; FLASH-PHOTOLYSIS; GLOBIN LINKAGE; SORET BAND AB The dynamic and functional properties of mutant deoxyhemoglobins in which either the beta-globin Val(67)(E11) or the alpha-globin Val(62)(E11) is replaced by threonine have been investigated through the thermal evolution of the Soret absorption band in the temperature range 300 to 20 K and through the kinetics of CO rebinding after flash photolysis at room temperature. The conformational properties of the modified alpha chain and beta chain distal heme pockets were also studied through x-ray crystallography and molecular modeling. The data obtained with the various techniques consistently indicate that the polar isosteric mutation in the distal side of the alpha chain heme pocket has a larger effect on the investigated properties than the analogous mutation on the beta chain. We attribute the observed differences to the presence of a water molecule in the distal heme pocket of the modified alpha chains, interacting with the hydroxyl of the threonine side chain. This is indicated by molecular modeling which showed that the water molecule present in the cu chain distal heme pocket can bridge by H bonding between Thr(62)(E11) and His(58)(E7) without introducing any unfavorable steric interactions. Consistent with the dynamic and functional data, the presence of a water molecule in the distal heme pocket of the modified beta chains is not observed by x-ray crystallography. C1 INFM, I-90123 PALERMO, ITALY. NCI, MOL CARCINOGENESIS LAB, NIH, BETHESDA, MD 20892 USA. UNIV MARYLAND, INST BIOTECHNOL, CTR ADV RES BIOTECHNOL, ROCKVILLE, MD 20850 USA. TEMPLE UNIV, DEPT CHEM, PHILADELPHIA, PA 19122 USA. UNIV MARYLAND, SCH MED, DEPT BIOCHEM & MOL BIOL, BALTIMORE, MD 21201 USA. RP Cupane, A (reprint author), UNIV PALERMO, IST FIS, VIA ARCHIRAFI 36, I-90123 PALERMO, ITALY. RI MILITELLO, VALERIA/F-2664-2011; Leone, Maurizio/F-2353-2010; Friedman, Fred/D-4208-2016 OI Leone, Maurizio/0000-0002-0292-7657; FU NHLBI NIH HHS [HLBI-48517] NR 46 TC 11 Z9 11 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 OCT 17 PY 1997 VL 272 IS 42 BP 26271 EP 26278 DI 10.1074/jbc.272.42.26271 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YB139 UT WOS:A1997YB13900030 PM 9334196 ER PT J AU Trumbore, MW Wang, RH Enkemann, SA Berger, SL AF Trumbore, MW Wang, RH Enkemann, SA Berger, SL TI Prothymosin alpha in vivo contains phosphorylated glutamic acid residues SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-TRANSDUCTION; BINDS HISTONES; RAT THYMUS; IN-VITRO; C-MYC; GENE; EXPRESSION; PROTEIN; NUCLEOPLASMIN; LOCALIZATION AB Human and monkey prothymosin alpha contain activated carbonyl groups on glutamic acid residues. Three lines of evidence indicate the existence of unusual phosphates. 1) Prothymosin alpha continued to be metabolically labeled with [P-32]orthophosphoric acid despite a mutation at Ser(1), the sole site of phosphate in purified bovine prothymosin alpha (Sburlati, A. R., De La Rosa, A., Batey D. W., Kurys, G. L., Manrow, R. E., Pannell, L. K., Martin, B. M., Sheeley, D. M., and Berger, S. L. (1993) Biochemistry 32, 4587-4596), 2) Immediately upon cell lysis, the pH stability curves of metabolically label ed native [P-32]prothymosin alpha or a [P-32]histidine-tagged variant resembled the pH stability curve of acetyl phosphate. 3) After a brief incubation at pH ?, these curves changed from a pattern diagnostic for an acyl phosphate to that characteristic of a serine or threonine phosphate, an observation consistent with transfer of phosphate in vitro. Our data indicate that most of prothymosin alpha's phosphates are subject instantaneously to hydrolysis, based on the observation that greater than 90% of the phosphate initially found at pH 7 disappeared at the extremes of pH. Rapid loss of phosphate was not affected by the presence of phosphatase inhibitors including 50 mM sodium fluoride, 1 mM okadaic acid, and 0.5 mM calyculin A. The amount of phosphate missing could not be ascertained, but the trifling amount recovered on Ser or Thr depended heavily on conditions favoring the transient survival of labile phosphate. Further analysis using COS cells lysed in the presence of sodium borohydride showed that: 1) phosphate recovered on prothymosin alpha decreased 8-fold when lysates were treated with borohydride; 2) the reagent caused 4-8 glutamic acid residues/molecule to vanish; 3) using [H-3]NaBH4, label was introduced into proline, a product derived from reductive cleavage of phosphoglutamate; and 4) [H-3]proline was localized almost exclusively to a peptide with pronounced homology to the histone binding site of nucleoplasmin, a chromatin remodeling protein found in Xenopus laevis. Our data demonstrate that prothymosin a is energy-rich by virtue of stoichiometric amounts of glutamyl phosphate. C1 NCI,SECT GENES & GENE PROD,NIH,BETHESDA,MD 20892. NR 59 TC 23 Z9 24 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 OCT 17 PY 1997 VL 272 IS 42 BP 26394 EP 26404 DI 10.1074/jbc.272.42.26394 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YB139 UT WOS:A1997YB13900048 PM 9334214 ER PT J AU Wang, RH Tao, L Trumbore, MW Berger, SL AF Wang, RH Tao, L Trumbore, MW Berger, SL TI Turnover of the acyl phosphates of human and murine prothymosin alpha in vivo SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; NUCLEAR-PROTEIN; MESSENGER-RNA; GENE; PHOSPHORYLATION; EXPRESSION; PRODUCTS; TISSUES; PROLIFERATION; PARATHYMOSIN AB Prothymosin alpha is a small, highly acidic, abundant, nuclear, mammalian protein which is essential for cell growth, Our laboratory has recently shown that primate prothymosin alpha contains stoichiometric amounts of phosphate on the glutamyl groups of the protein and that in vitro the phosphate undergoes rapid hydrolysis or transfer to a nearby serine residue, Here an assay for the presence of acyl phosphates in vivo has been developed by measuring stable phosphoserine and phosphothreonine in. vitro, The assay was used to determine the half-life of the acyl phosphates on prothymosin alpha in vivo by pulse-labeling HeLa cells with [P-32]orthophosphate and chasing using three different techniques: permeabilization with digitonin to allow extracellular ATP to equilibrate with the intracellular pool; electroporation in the presence of ATP to reduce the specific activity of [P-32]ATP by expansion of the pool; and incubation with inorganic phosphate, Regardless of the method, the phosphate turned over with a half-life of 75-90 min. The ability of cells to phosphorylate old prothymosin alpha molecules was established by demonstrating equivalent labeling of the protein with [P-32]orthophosphate in the presence and absence of cycloheximide. The half-life of the acyl phosphates was also studied in resting and growing NIH3T3 cells, with measured values of 30-35 and 70 min, respectively. Our data suggest that the ''activity'' of prothymosin alpha involves the turnover of its acyl phosphates and that it participates in a function common to all nucleated mammalian cells regardless of whether they are quiescent or undergoing rapid proliferation, This is the first measurement of the stability of protein-bound acyl phosphates in vivo. C1 NCI,SECT GENES & GENE PROD,NIH,BETHESDA,MD 20892. NR 40 TC 23 Z9 23 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 OCT 17 PY 1997 VL 272 IS 42 BP 26405 EP 26412 DI 10.1074/jbc.272.42.26405 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YB139 UT WOS:A1997YB13900049 PM 9334215 ER PT J AU Pourquier, P Pilon, AA Kohlhagen, G Mazumder, A Sharma, A Pommier, Y AF Pourquier, P Pilon, AA Kohlhagen, G Mazumder, A Sharma, A Pommier, Y TI Trapping of mammalian topoisomerase I and recombinations induced by damaged DNA containing nicks or gaps - Importance of DNA end phosphorylation and camptothecin effects SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ILLEGITIMATE RECOMBINATION; EUKARYOTIC TOPOISOMERASE; BINDING SEQUENCE; CLEAVAGE SITES; DUPLEX DNA; STRAND; INHIBITORS; CELL; BASE; REPLICATION AB We used purified mammalian topoisomerases I (top1) and oligonucleotides containing a unique top1 cleavage site to study top1-mediated cleavage and recombination in the presence of nicks and short gaps mimicking DNA damage, In general, top1 cleavage was not induced opposite to the nicks, and nicks upstream from the top1 cleavage site suppressed top1 activity, Irreversible top1 cleavage complexes (''suicide products'' or ''aborted complexes'') were produced in DNA containing nicks or short gaps just opposite to the normal top1 cleavage site, Camptothecin enhanced the formation of the aborted top1 complexes only for nicks downstream from the cleavage site, These aborted (suicide) complexes can mediate DNA recombination and promote illegitimate recombination by catalyzing the ligation of nonhomologous DNA fragments (accepters), We report for the first time that top1-mediated recombination is greatly en enhanced by the presence of a phosphate at the 5' terminus of the top1 aborted complex (donor DNA), By contrast, phosphorylation of the 3' terminus of the gap did not affect recombination, At concentrations that strongly enhanced inhibition of intramolecular religation, resulting in an increase of top1 cleavable complexes, camptothecin did not reduce recombination (intermolecular religation). Nicks or gaps with 5'-phosphate termini would be expected to be produced directly by ionizing radiations or by processing of abasic sites and DNA lesions induced by carcinogens or drugs used in cancer chemotherapy, Thus, these results further demonstrate that DNA damage can efficiently trap top1-cleavable complexes and enhance top1 mediated DNA recombination. C1 NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 47 TC 132 Z9 133 U1 1 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 OCT 17 PY 1997 VL 272 IS 42 BP 26441 EP 26447 DI 10.1074/jbc.272.42.26441 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YB139 UT WOS:A1997YB13900054 PM 9334220 ER PT J AU Caloca, MJ Fernandez, N Lewin, NE Ching, DX Modali, R Blumberg, PM Kazanietz, MG AF Caloca, MJ Fernandez, N Lewin, NE Ching, DX Modali, R Blumberg, PM Kazanietz, MG TI beta 2-chimaerin is a high affinity receptor for the phorbol ester tumor promoters SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; GTPASE-ACTIVATING PROTEIN; CYSTEINE-RICH REGION; MOUSE-BRAIN; N-CHIMAERIN; 12,13-DIBUTYRATE BINDING; CAENORHABDITIS-ELEGANS; SIGNAL-TRANSDUCTION; CALCIUM; ISOZYMES AB beta 2-chimaerin, a member of the GTPase-activating proteins for the small GTP-binding protein p21Rac, possesses a single cysteine-rich domain with high homology to those implicated in phorbol ester and diacylglycerol binding in protein kinase C (PKC) isozymes. We have expressed beta 2-chimaerin in Sf9 insect cells using the baculovirus expression system and determined that, like PKCs, beta 2-chimaerin binds phorbol esters with high affinity in the presence of phosphatidylserine as a cofactor. Scatchard plot analysis using the radioligand [H-3]phopbol 12,13-dibutyrate revealed a dissociation constant of 1.9 +/- 0.2 nM for beta 2-chimaerin. Likewise, beta 2-chimaerin is a high affinity receptor for the bryostatins, a class of atypical PHC activators. A detailed comparison of structure activity relations using several phorbol ester analogs revealed striking differences in binding recognition between beta 2-chimaerin and PKC alpha. Although the diacylglycerol 1-oleoyl-2-acetylglycerol binds with similar potency to both beta 2-chimaerin and PKC alpha; the mezerein analog thymeleatoxin has 56-foId less affinity for binding to beta 2-chimaerin. To establish whether beta 2-chimaerin responds to phorbol esters in cellular sys-- tems, we overexpressed beta 2-chimaerin in COS-7 cells and monitored its subcellular distribution after phorbol ester treatment. Interestingly, as described previously for PI(C isozymes, beta 2-chimaerin translocates from cytosolic to particulate fractions as a consequence of phorbol ester treatment. Our results demonstrate that beta 2-chimaerin is a novel target for the phorbol aster tumor promoters. The expansion of the family of phorbol ester receptors strongly suggests a potential for the ''nonkinase'' receptors as cellular mediators of the phorbol ester responses. C1 UNIV PENN, SCH MED, CTR EXPT THERAPEUT, STELLAR CHANCE LABS 905, PHILADELPHIA, PA 19104 USA. UNIV PENN, SCH MED, DEPT PHARMACOL, PHILADELPHIA, PA 19104 USA. NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, NIH, BETHESDA, MD 20892 USA. BIOSERVE BIOTECHNOL, LAUREL, MD 20707 USA. RI Caloca, Maria-Jose/K-9357-2014; OI Caloca, Maria-Jose/0000-0002-1003-2685 FU NCI NIH HHS [IROICA74197-OIAI] NR 42 TC 84 Z9 84 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 OCT 17 PY 1997 VL 272 IS 42 BP 26488 EP 26496 DI 10.1074/jbc.272.42.26488 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YB139 UT WOS:A1997YB13900060 PM 9334226 ER PT J AU Seok, YJ Sondej, M Badawi, P Lewis, MS Briggs, MC Jaffe, H Peterkofsky, A AF Seok, YJ Sondej, M Badawi, P Lewis, MS Briggs, MC Jaffe, H Peterkofsky, A TI High affinity binding and allosteric regulation of Escherichia coli glycogen phosphorylase by the histidine phosphorylase protein, HPr SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CONTAINING PHOSPHOCARRIER PROTEIN; SUGAR PHOSPHOTRANSFERASE SYSTEM; GRAM-POSITIVE BACTERIA; SALMONELLA-TYPHIMURIUM; RESOLUTION STRUCTURE; GENE; PHOSPHOENOLPYRUVATE; PURIFICATION; SEQUENCE; OPERON AB The histidine phosphocarrier protein (HPr) is an essential element in sugar transport by the bacterial phosphoenolpyruvate:sugar phosphotransferase system, Ligand fishing, using surface plasmon resonance, was used to show the binding of HPr to a nonphosphotransferase protein in extracts of Escherichia coli; the protein was subsequently identified as glycogen phosphorylase (GP), The high affinity (association constant similar to 10s M-1), species-specific interaction was also demonstrated in electrophoretic mobility shift experiments by polyacrylamide gel electrophoresis, Equilibrium ultracentrifugation analysis indicates that HPr allosterically regulates the oligomeric state of glycogen phosphorylase. HPr binding increases GP activity to 250% of the level in control assays, Kinetic analysis of coupled enzyme as says shows that the binding of HPr to GP causes a decrease in the K-m for glycogen and an increase in the V-max for phosphate, indicating a mixed type activation, The stimulatory effect of E, coli HPr on E, coli GP activity is species-specific, and the unphosphorylated form of HPr activates GP more than does the phosphorylated form, Replacement of specific amino acids in]HPr results in reduced GP activation; HPr residues Arg-17, Lys-24, Lys-27, Lys-40, Ser-46, Gln-51, and Lys-72 were established to be important, This novel mechanism for the regulation of GP provides the first evidence directly linking E, coli HPr to the regulation of carbohydrate metabolism. C1 NHLBI,NIH,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,BETHESDA,MD 20892. NINCDS,NIH,BETHESDA,MD 20892. NR 49 TC 71 Z9 72 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 OCT 17 PY 1997 VL 272 IS 42 BP 26511 EP 26521 DI 10.1074/jbc.272.42.26511 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YB139 UT WOS:A1997YB13900063 PM 9334229 ER PT J AU Ribeiro, CMP Reece, J Putney, JW AF Ribeiro, CMP Reece, J Putney, JW TI Role of the cytoskeleton in calcium signaling in NIH 3T3 cells - An intact cytoskeleton is required for agonist-induced [Ca2+](i) signaling, but not for capacitative calcium entry SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INTERNAL CA2+ RELEASE; PAROTID ACINAR-CELLS; ENDOPLASMIC-RETICULUM; INOSITOL 1,4,5-TRISPHOSPHATE; PLASMA-MEMBRANE; ACTIN-FILAMENTS; RECEPTOR; ANKYRIN; INFLUX; REORGANIZATION AB Treatment of NIH 3T3 cells with cytochalasin D (10 mu M, 1 h at 37 degrees C) disrupted the actin cytoskeleton and changed the cells from a planar, extended morphology, to a rounded shape, Calcium mobilization by ATP or by platelet-derived growth factor was abolished, while the ability of thapsigargin (2 mu M) to empty calcium stores and activate calcium influx was unaffected, Similar experiments with nocodazole to depolymerize the tubulin network yielded identical results, Platelet-derived growth factor induced an increase in inositol phosphates, and this increase was undiminished in the presence of cytochalasin D, Therefore, the blockade of agonist responses by this drug does not result from decreased phospholipase C, Injection of inositol 1,4,5-trisphosphate (IP3) released calcium to the same extent in control and cytochalasin D-treated cells. Confocal microscopic studies revealed a significant rearrangement of the endoplasmic reticulum after cytochalasin D treatment, Thus, disruption of the cytoskeleton blocks agonist-elicited [Ca2+](i) mobilization, but this effect does not result from a lower calcium storage capacity, impaired function of the IP3 receptor, or diminished phospholipase C activity, We suggest that cytoskeletal disruption alters the spatial relationship between phospholipase C and IP3 receptors, impairing phospholipase C-dependent calcium signaling, Capacitative calcium entry was not altered under these conditions, indicating that the coupling between depletion of intracellular calcium stores and calcium entry does not depend on a precise structural relationship between intracellular stores and plasma membrane calcium channels. RP Ribeiro, CMP (reprint author), NIEHS,LAB SIGNAL TRANSDUCT,NIH,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Ribeiro, Carla Maria/A-6955-2009 NR 36 TC 123 Z9 125 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 OCT 17 PY 1997 VL 272 IS 42 BP 26555 EP 26561 DI 10.1074/jbc.272.42.26555 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YB139 UT WOS:A1997YB13900069 PM 9334235 ER PT J AU Giannini, G Dawson, MI Zhang, XK Thiele, CJ AF Giannini, G Dawson, MI Zhang, XK Thiele, CJ TI Activation of three distinct RXR/RAR heterodimers induces growth arrest and differentiation of neuroblastoma cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RETINOIC ACID RECEPTOR; HUMAN NEURO-BLASTOMA; X-RECEPTOR; N-MYC; BINDING-PROTEINS; THYROID-HORMONE; NUCLEAR RECEPTORS; RESPONSE ELEMENT; RXR-ALPHA; RAR-ALPHA AB Naturally occurring retinoids, like all-trans retinoic acid and 9-cis retinoic acid, are known to affect proliferation and differentiation of sensitive neuroblastoma cell lines. Cellular responsiveness to retinoic acid depends on its interaction with two distinct classes of receptors, the retinoic acid receptors (RARs) and the retinoic X receptors (RXRs). Both receptor classes have three different subtypes (RAR alpha, RAR beta, and RAR gamma and RXR alpha, RAR beta, and RAR gamma) that act as ligand-dependent transcription factors. To examine the involvement of the different receptor classes and subtypes in the biological responses of neuroblastoma cells to retinoids, we analyzed the effects of a panel of receptor selective retinoids on cell growth, differentiation, and gene expression on in vitro cultured KCNR cells. Any association of per se inactive RXR-selective with RAR-selective ligands efficiently regulates growth inhibition, differentiation (neurite extension), and expression of RAR beta, TrkB, and N-myc. SR11383 alone, a very potent retinoid, entirely reproduces the pattern of biological responses induced by naturally occurring retinoids, In contrast to other tumor cell lines, the growth of neuroblastoma cell lines is not altered using AP1-antagonistic retinoids. These studies raise the possibility that three distinct RXR/RAR heterodimers mediate the effects of retinoids on neuroblastoma cells through an AP-1 antagonism-independent mechanism. C1 NCI,CELL & MOL BIOL SECT,PEDIAT ONCOL BRANCH,NIH,BETHESDA,MD 20892. SRI INT,RETINOID PROGRAM,MENLO PK,CA 94025. BURNHAM INST,LA JOLLA,CA 92037. RI Giannini, Giuseppe/B-5672-2013 OI Giannini, Giuseppe/0000-0003-0299-4056 NR 55 TC 44 Z9 46 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 OCT 17 PY 1997 VL 272 IS 42 BP 26693 EP 26701 DI 10.1074/jbc.272.42.26693 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YB139 UT WOS:A1997YB13900087 PM 9334253 ER PT J AU Sheikh, MS Carrier, F Papathanasiou, MA Hollander, MC Zhan, QM Yu, K Fornace, AJ AF Sheikh, MS Carrier, F Papathanasiou, MA Hollander, MC Zhan, QM Yu, K Fornace, AJ TI Identification of several human homologs of hamster DNA damage-inducible transcripts - Cloning and characterization of a novel UV-inducible cDNA that codes for a putative RNA-binding protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSLATION INITIATION FACTOR-5; CELL NUCLEAR ANTIGEN; MESSENGER-RNA; RECOGNITION MOTIF; MAMMALIAN-CELLS; EXCISION-REPAIR; LEUKEMIA-CELLS; GENE; INDUCTION; GROWTH AB Low Patio hybridization subtraction technique was previously used in this laboratory to enrich and isolate a number of low abundance UV-inducible hamster transcripts (Fornace, A. J., Jr., Alamo, I. J., and Hollander, M. C. (1988) Proc. Natl. Acad, Sci. U. S. A. 85, 8800-8804) that led to the identification and cloning of five important hamster and human GADD genes (Fornace, A. J., Jr., Nebert, D. W., Hollander, M. C,, Luethy, J. D., Papathanasiou, M., Fargnoli, J., and Holbrook, N. J. (1989) Mol, Cell. Biol. 9, 4196-4205), In this study we have characterized the remaining DNA damage-inducible (DDI) transcripts. Of the 24 DDI clones, 3 clones (A13, A20, and A113) representing different regions of the same hamster cDNA exhibited near perfect homology to human p21(WAF1/CIP1) cDNA. The DDI clones A26, A88, and A99 displayed very high sequence homologies with the human proliferating nuclear antigen, rat translation initiation factor-5 (eIF-5), and human thrombomodulin, respectively, whereas clones A29 and A121 matched with express sequence tagged sequences of unknown identity, The DDI clones A18, 106, and A107 were different isolates of the same hamster cDNA (hereafter referred to as A18) and displayed high sequence homology with the members in the heterogeneous ribonucleoprotein (hnRNP) family, Using the hamster A18 partial-length cDNA as a probe, we screened human fibroblast cDNA library and isolated the corresponding full-length human cDNA. The deduced amino acid sequence revealed that the putative protein contains all the canonical features of a novel glycine-rich hnRNP. The A18 mRNA levels mere specifically increased in response to DNA damage induced by UV irradiation or UV mimetic agents, Thus the putative A18 hnRNP is the first hnRNP whose mRNA is specifically regulated in response to UV-induced DNA damage; accordingly, it may play some role in repair of W-type DNA damage. RP Sheikh, MS (reprint author), NCI,MOL PHARMACOL LAB,NIH,BLDG 37,RM 5D02,BETHESDA,MD 20892, USA. RI Carrier, France/C-3063-2008; Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 47 TC 50 Z9 56 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 OCT 17 PY 1997 VL 272 IS 42 BP 26720 EP 26726 DI 10.1074/jbc.272.42.26720 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YB139 UT WOS:A1997YB13900091 PM 9334257 ER PT J AU Kristie, TM AF Kristie, TM TI The mouse homologue of the human transcription factor C1 (host cell factor) - Conservation of forms and function SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HERPES-SIMPLEX VIRUS; VP16 ACCESSORY PROTEIN; ALPHA-GENES; DNA COMPLEX; POU DOMAIN; CIS SITE; OCT-1; BINDING; INDUCTION; RECOGNITION AB The assembly of the herpes simplex virus (HSV) alpha/IE gene enhancer complex is determined by the interactions of the Oct-1 POU domain protein, the viral alpha TIF (alpha-trans-induction factor, VP16, ICP25, VMW65), and the C1 factor (host cell factor, HCF). A unique transcription factor, C1 consists of a family of polypeptides derived from a common precursor by site-specific proteolytic processing. To analyze the role of this factor in the determination of HSV lytic-latent infection, cDNAs and genomic DNAs encoding the mouse homologue have been isolated. This factor is nearly identical to the human protein, contains multiple consensus proteolytic processing sites, and functions efficiently in the assembly of a specific HSV enhancer complex. Interestingly, the differential expression of the C1 factors in both human and mouse tissues may be important for the determination of HSV tissue tropism in these two organisms. RP Kristie, TM (reprint author), NIAID,VIRAL DIS LAB,NIH,BLDG 4,RM 133,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 38 TC 18 Z9 19 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 OCT 17 PY 1997 VL 272 IS 42 BP 26749 EP 26755 DI 10.1074/jbc.272.42.26749 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YB139 UT WOS:A1997YB13900095 PM 9334261 ER PT J AU Clubb, RT Schumacher, S Mizuuchi, K Gronenborn, AM Clore, GM AF Clubb, RT Schumacher, S Mizuuchi, K Gronenborn, AM Clore, GM TI Solution structure of the I gamma subdomain of the Mu end DNA-binding domain of phage Mu transposase SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE phage Mu; transposase; I gamma subdomain; solution structure; helix-turn-helix ID PROTEIN-STRUCTURE DETERMINATION; DIRECT REFINEMENT; CRYSTAL-STRUCTURE; CHEMICAL-SHIFTS; NMR; SPECTROSCOPY; RESOLUTION; IMPACT; MOTIF; OCT-1 AB The MuA transposase of phase Mu is a large modular protein that plays a central role in transposition. We show that the Mu end DNA-binding domain, I beta gamma, which is responsible for binding the DNA attachment sites at each end of the Mu genome, comprises two subdomains, I beta and I gamma, that are structurally autonomous and do not interact with each other in the absence of DNA. The solution structure of the I gamma subdomain has been determined by multidimensional NMR spectroscopy. The structure of I gamma comprises a four helix bundle and, despite the absence of any significant sequence identity, the topology of the first three helices is very similar to that of the homeodomain family of helix-turn-helix DNA-binding proteins. The helix-turn-helix motif of I gamma, however, differs from that of the homeodomains in so far as the loop is longer and the second helix is shorter, reminiscent of that in the POU-specific domain. (C) 1997 Academic Press Limited. C1 NIDDKD,PHYS CHEM LAB,NIH,BETHESDA,MD 20892. NIDDKD,MOL BIOL LAB,NIH,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 32 TC 29 Z9 31 U1 0 U2 1 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 OCT 17 PY 1997 VL 273 IS 1 BP 19 EP 25 DI 10.1006/jmbi.1997.1312 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YC180 UT WOS:A1997YC18000004 PM 9367742 ER PT J AU Sikorski, R Peters, R AF Sikorski, R Peters, R TI Microsoft macrovirology SO SCIENCE LA English DT Editorial Material C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Sikorski, R (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 17 PY 1997 VL 278 IS 5337 BP 503 EP 503 DI 10.1126/science.278.5337.503 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YB355 UT WOS:A1997YB35500058 ER PT J AU TomoaiaCotisel, M Levin, IW AF TomoaiaCotisel, M Levin, IW TI Thermodynamic study of the effects of ursodeoxycholic acid and ursodeoxycholate on aqueous dipalmitoyl phosphatidylcholine bilayer dispersions SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID MICELLE-VESICLE TRANSITION; LECITHIN MIXED MICELLES; CHARGED LIPID-MEMBRANES; BILE-SALT; PHASE-TRANSITION; DIPALMITOYLPHOSPHATIDYLCHOLINE LIPOSOMES; LIGHT-SCATTERING; CHAIN-LENGTH; MIXTURES; WATER AB The effects of ursodeoxycholic acid (UDCAH) and ursodeoxycholate (UDCA(-)) on the thermotropic phase behavior of aqueous bilayer dispersions of 1,2-dipalmitoyl-3-sn-phosphatidylcholine (DPPC), buffered at pH 7.0, were examined by differential scanning calorimetry (DSC) for concentrations of UDCAH and UDCA(-) (represented by UDCA) from 0 to approximately 76 mol %. The calorimetric data show that progressively increasing UDCA concentrations decreases the DPPC bilayer main transition temperatures (T-m), while increasing the widths of the gel to liquid crystalline phase transition endotherms. The DPPC bilayer pretransition is suppressed in the presence of UDCA at the Lowest concentrations employed. The calorimetric data, which are interpreted in terms of the partition equilibria of UDCAH and UDCA(-) and of the DPPC bilayer phase transition enthalpies and Gibbs free energies, allow the development of a thermodynamic approach for determining the phase boundaries in mixed DPPC:UDCA dispersions. In particular, for concentrations of UDCA up to approximately 25 mol %, the gel to liquid crystalline phase transition enthalpies of the mixed DPPC:UDCA bilayers remain essentially constant. The increase that occurs in the DPPC gel to liquid crystalline phase transition enthalpies for UDCA concentrations between approximately 25-60 mol % is interpreted in terms of an induced interdigitated gel (L-gI) phase stabilized by specific DPPC:UDCA molecular interactions. The data suggest that the interdigitated gel phase exists in equilibrium with micelles, whose structures remain to be elucidated, of various UDCA:DPPC mole ratios. Finally, concentrations of UDCA in amounts greater than 60 mol % result in constant DPPC phase transition temperatures and enthalpies. C1 NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. NR 53 TC 11 Z9 11 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1089-5647 J9 J PHYS CHEM B JI J. Phys. Chem. B PD OCT 16 PY 1997 VL 101 IS 42 BP 8477 EP 8485 DI 10.1021/jp970990j PG 9 WC Chemistry, Physical SC Chemistry GA YB794 UT WOS:A1997YB79400012 ER PT J AU Wilson, WH AF Wilson, WH TI Chemotherapy for AIDS-related lymphomas SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID DOSE INTENSITY RP Wilson, WH (reprint author), NCI,BETHESDA,MD 20892, USA. NR 4 TC 2 Z9 2 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 OCT 16 PY 1997 VL 337 IS 16 BP 1172 EP 1173 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA YA912 UT WOS:A1997YA91200021 PM 9340511 ER PT J AU Blagosklonny, MV AF Blagosklonny, MV TI Loss of function and p53 protein stabilization SO ONCOGENE LA English DT Review DE p53; stabilization; mutant; transactivating function ID TUMOR-SUPPRESSOR PROTEIN; CANCER CELL-LINES; MUTANT P53; SV40-TRANSFORMED CELLS; TRANSFORMED-CELLS; BREAST-CANCER; METABOLIC STABILIZATION; ACTIVATING MUTATIONS; DNA-BINDING; T-ANTIGEN AB Wild-type (wt) p53 protein is rapidly degraded, has a short half-life and low intracellular levels. Stabilization of wt p53 protein following an appropriate stimulus (for example DNA damage) is a physiological regulation to increase function. Tn contrast, stabilization of p53 protein in the absence of a stimulus is always a hallmark of loss of function secondary to a mutation, or interaction with viral or cellular oncoproteins. It is generally accepted that stability of p53 protein depends on its intrinsic biochemical properties such as conformation or protein/protein interactions. However, I will discuss evidence that the stability of p53 is not a consequence of its intrinsic properties, but instead is determined by feedback control of its function. In the absence of an appropriate stimulus, a cell needs to keep p53 levels low, since increased levels can lead to apoptosis. To precisely regulate p53 levels, a cell must sense its level; and sensing its transactivating function, is the simplest way to sense p53. Following an appropriate stimulus (for example, DIVA damage), the cell senses a state of 'relative' p53 deficiency and adapts by reducing p53 degradation. When the state of p53 deficiency is a consequence of a mutation or interaction with viral oncoproteins, the cell does not sense p53, and again attempts to adapt by reducing p53 degradation. However, in the latter case, the increase in levels does not restore function, and the adaptation continues until degradation of p53 protein is maximally inhibited. In this case, no further inhibition of degradation is possible after DNA-damage or pharmacological inhibition of proteasomes. Thus lack of wt p53 function always results in increased p53 levels and nonregulation. RP Blagosklonny, MV (reprint author), NCI,MED BRANCH,NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 67 TC 104 Z9 105 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 16 PY 1997 VL 15 IS 16 BP 1889 EP 1893 DI 10.1038/sj.onc.1201374 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA YA872 UT WOS:A1997YA87200002 PM 9365234 ER PT J AU Baskaran, K Erfurth, F Taborn, G Copeland, NG Gilbert, DJ Jenkins, NA Iannaccone, PM Domer, PH AF Baskaran, K Erfurth, F Taborn, G Copeland, NG Gilbert, DJ Jenkins, NA Iannaccone, PM Domer, PH TI Cloning and developmental expression of the murine homolog of the acute leukemia proto-oncogene AF4 SO ONCOGENE LA English DT Article DE AF4; MLL; acute leukemia; transcription factor ID BONE MORPHOGENETIC PROTEIN-4; DIFFERENTIAL EXPRESSION; PROMYELOCYTIC LEUKEMIA; DROSOPHILA-TRITHORAX; TRANSCRIPTION FACTOR; BINDING DOMAINS; GENE-EXPRESSION; MICE LACKING; DNA-BINDING; ALL-1 GENE AB AF4 is the 4q21 gene involved in the acute lymphoblastic leukemia associated t(4;11)(q21;q23) where it forms a fusion gene with MLL, In order to gain insight into AF4's role in leukemogenesis we have studied its functional domains and expression pattern during murine development, We have cloned the murine homolog, Af4. We have demonstrated that 5' half of Af4 encodes a region with transcriptional transactivation activity which is disrupted by the t(4;11) in human leukemias, We have also localized the murine AF4 protein to the nucleus supporting a role for AF4 in transcription, The developmental expression pattern of Af4 was determined in situ hybridization and suggests Af4 plays an important role in the development of the hematopoietic, cardiovascular, skeletal and central nervous systems, A repeating pattern of Af4 expression in development is downregulation with differentiation of a tissue, Among the cell types where this pattern of down-regulation is noted are B-lymphocytes. These findings raise the possibility that the disruption of normal AF4 function by the translocation may contribute to leukemogenesis. C1 UNIV CHICAGO,DEPT PATHOL,CHICAGO,IL 60637. NORTHWESTERN UNIV,SCH MED,DEPT PEDIAT,CHILDRENS MEM INST EDUC & RES,CHICAGO,IL 60614. FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [R29 CA 65911-01] NR 57 TC 20 Z9 20 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 16 PY 1997 VL 15 IS 16 BP 1967 EP 1978 DI 10.1038/sj.onc.1201365 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA YA872 UT WOS:A1997YA87200011 PM 9365243 ER PT J AU Cardillo, C Kilcoyne, CM Quyyumi, AA Cannon, RO Panza, JA AF Cardillo, C Kilcoyne, CM Quyyumi, AA Cannon, RO Panza, JA TI Role of nitride oxide in the vasodilator response to mental stress in normal subjects SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ENDOTHELIUM-DEPENDENT VASODILATION; FOREARM RESISTANCE VESSELS; FLOW; RELAXATION; ARTERIES; RELEASE; HUMANS AB Vascular production of nitric oxide (NO) plays an important role in a variety of physiologic processes, This study examines the contribution of NO to the vasodilator response to mental stress. The effects of mental arithmetic testing on forearm vascular dynamics were analyzed in 15 normal subjects (9 men; age 45 +/- 12 years) during intraarterial infusion of either saline or N-G-mono-methyl-L-arginine (L-NMMA; 4 mu mol/min for 15 minutes), an inhibitor of NO synthesis. The effect of L-NMMA on endothelium-independent vasodilation induced by intraarterial infusion of sodium nitroprusside was also studied in 11 of the 15 subjects, Forearm blood flow was measured by plethysmography. Mental stress increased forearm blood flow from 2.35 +/- 0.84 to 5.06 +/- 2.66 ml/min/dl (115%) during saline and from 1.72 +/- 0.59 to 2.81 +/- 0.99 ml/min/dl (63%) during L-NMMA infusion, The vasodilator effect of mental stress was significantly lower during L-NMMA infusion than during saline (1.1 +/- 0.65 vs 2.71 +/- 2.15 ml/min/dl; p = 0.01), L-NMMA administration did not significantly change mean arterial pressure and heart rate responses to mental stress. In contrast, the vasodilator effect of sodium nitroprusside (1.6 mu g/min) was similar during infusion of L-NMMA and during saline (3.75 +/- 1.55 vs 2.85 +/- 1.38 ml/min/dl; p = 0.16), These findings indicate that local release of NO is involved in the forearm vasodilatar response to mental stress. (C) 1997 by Excerpta Medica, Inc. C1 NHLBI,CARDIOL BRANCH,NIH,BETHESDA,MD 20892. NR 22 TC 47 Z9 50 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 15 PY 1997 VL 80 IS 8 BP 1070 EP 1074 DI 10.1016/S0002-9149(97)00605-X PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YB392 UT WOS:A1997YB39200018 PM 9352980 ER PT J AU Garcia, LJ Rosado, JA Gonzalez, A Jensen, RT AF Garcia, LJ Rosado, JA Gonzalez, A Jensen, RT TI Cholecystokinin-stimulated tyrosine phosphorylation of p125(FAK) and paxillin is mediated by phospholipase C-dependent and -independent mechanisms and requires the integrity of the actin cytoskeleton and participation of p21(rho) SO BIOCHEMICAL JOURNAL LA English DT Article ID SWISS 3T3 CELLS; FOCAL ADHESION KINASE; ACTIVATED PROTEIN-KINASE; PANCREATIC ACINAR-CELLS; GUINEA-PIG PANCREAS; GTP-BINDING PROTEIN; ADP-RIBOSYLTRANSFERASE; BOMBESIN STIMULATION; EXTRACELLULAR-MATRIX; THAPSIGARGIN DEFINES AB Recent studies show that the effects of some oncogenes, integrins, growth factors and neuropeptides are mediated by tyrosine phosphorylation of the cytosolic kinase p125 focal adhesion kinase (p125(FAK)) and the cytoskeletal protein paxillin. Recently we demonstrated that cholecystokinin (CCK) C-terminal octapeptide (CCK-8) causes tyrosine phosphorylation of p125(FAK) and paxillin in rat pancreatic acini. The present study was aimed at examining whether protein kinase C (PKC) activation, calcium mobilization, cytoskeletal organization and small G-protein p21(rho) activation play a role in mediating the stimulation of tyrosine phosphorylation by CCK-8 in acini. CCK-8-stimulated phosphorylation of p125(FAK) and paxillin reached a maximum within 2.5 min. The CCK-8 dose response for causing changes in the cytosolic calcium concentration ([Ca2+](i)) was similar to that for p125(FAK) and paxillin phosphorylation, and both were to the left of that for receptor occupation and inositol phosphate production. PMA increased tyrosine phosphorylation of both proteins. The calcium ionophore A23187 caused only 25 % of the maximal stimulation caused by CCK-8. GF109203X, a PKC inhibitor, completely inhibited phosphorylation with PMA but had no effect on the response to CCK-g. Depletion of [Ca2+](i) by thapsigargin had no effect on CCK-8-stimulated phosphorylation. Pretreatment with both GF109203X and thapsigargin decreased CCK-8-stimulated phosphorylation of both proteins by 50 %. Cytochalasin D, but not colchicine, completely inhibited CCK-8- and PMA-induced p125(FAK) and paxillin phosphorylation. Treatment with Clostridium botulinum C3 transferase, which inactivates p21(rho), caused significant inhibition of CCK-8-stimulated p125(FAK) and paxillin phosphorylation. These results demonstrate that, in pancreatic acini, CCK-8 causes rapid p125(FAK) and paxillin phosphorylation that is mediated by bath phospholipase C-dependent and -independent mechanisms. For this tyrosine phosphorylation to occur, the integrity of the actin, but not the microtubule, cytoskeleton is essential as well as the activation of p21(rho). C1 NIDDKD,DIGEST DIS BRANCH,NIH,BETHESDA,MD 20892. UNIV EXTREMADURA,DEPT PHYSIOL,CACERES 10080,SPAIN. RI Garcia-Marin, Luis /L-4680-2014; rosado, juan/H-3488-2015 OI Garcia-Marin, Luis /0000-0002-1795-7381; rosado, juan/0000-0002-9749-2325 NR 67 TC 63 Z9 64 U1 0 U2 2 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD OCT 15 PY 1997 VL 327 BP 461 EP 472 PN 2 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YC390 UT WOS:A1997YC39000021 PM 9359417 ER PT J AU Albert, C Safrany, ST Bembenek, ME Reddy, KM Reddy, KK Falck, JR Brocker, M Shears, SB Mayr, GW AF Albert, C Safrany, ST Bembenek, ME Reddy, KM Reddy, KK Falck, JR Brocker, M Shears, SB Mayr, GW TI Biological variability in the structures of diphosphoinositol polyphosphates in Dictyostelium discoideum and mammalian cells SO BIOCHEMICAL JOURNAL LA English DT Article ID INOSITOL POLYPHOSPHATES; PHOSPHOINOSITOL DIPHOSPHATES; PANCREATOMA CELLS; TETRAKISPHOSPHATE; PENTAKISPHOSPHATE; HEXAKISPHOSPHATE; METABOLISM; TURNOVER; COATOMER AB Previous structural analyses of diphosphoinositol polyphosphates in biological systems have relied largely on NMR analysis. For example, in Dictyostelium discoideum, diphosphoinositol pentakisphosphate was determined by NMR to be 4- and/or 6-PPInsP(5), and the bisdiphosphoinositol tetrakisphosphate was found to be 4,5-bisPPInsP(4) and/or 5,6-bisPPInsP(4) [Laussmann, Eujen, Weisshuhn, Thiel and Vogel (1996) Biochem. J. 315, 715-720]. We now describe three recent technical developments to aid the analysis of these compounds, not just in Dictyostelium, but also in a wider range of biological systems: (i) improved resolution and sensitivity of detection of PPInsP(5) isomers by microbore metal-dye-detection HPLC; (ii) the use of the enantiomerically specific properties of a rat hepatic diphosphatase; (iii) chemical synthesis of enantiomerically pure reference standards of all six possible PPInsP(5) isomers. Thus we now demonstrate that the major PPInsP, isomer in Dictyostelium is 6-PPInsP(5). Similar findings obtained using the same synthetic standards have been published [Laussmann, Reddy, Reddy, Falck and Vogel (1997) Biochem. J. 322, 31-33]. In addition, we show that 10-25% of the Dictyosrelium PPInsP(5) pool is comprised of 5-PPInsP(5). The biological significance of this new observation was reinforced by our demonstration that 5-PPInsP, is the pre dominant PPInsP, isomer in four different mammalian cell lines (FTC human thyroid cancer cells, Swiss 3T3 fibroblasts, Jurkat T-cells and Chinese hamster ovary cells). The fact that the cellular spectrum of diphosphoinositol polyphosphates varies across phylogenetic boundaries underscores the value of our technological developments for future determinations of the structures of this class of compounds in other systems. C1 NIEHS,LAB SIGNAL TRANSDUCT,INOSITOL LIPID SECT,RES TRIANGLE PK,NC 27709. DUPONT CO INC,MED PROD DIV,BOSTON,MA 02118. UNIV TEXAS,SW MED CTR,DEPT BIOCHEM,DALLAS,TX 75235. UNIV TEXAS,SW MED CTR,DEPT PHARMACOL,DALLAS,TX 75235. RUHR UNIV BOCHUM,HOSP BERGMANNSHEIL,D-44789 BOCHUM,GERMANY. OI Falck, John/0000-0002-9219-7845 FU NIGMS NIH HHS [GM31278] NR 25 TC 57 Z9 59 U1 2 U2 3 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD OCT 15 PY 1997 VL 327 BP 553 EP 560 PN 2 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YC390 UT WOS:A1997YC39000033 PM 9359429 ER PT J AU Malhotra, AK Adler, CM Kennison, SD Elman, I Pickar, D Breier, A AF Malhotra, AK Adler, CM Kennison, SD Elman, I Pickar, D Breier, A TI Clozapine blunts N-methyl-D-aspartate antagonist-induced psychosis: A study with ketamine SO BIOLOGICAL PSYCHIATRY LA English DT Article DE ketamine; atypical antipsychotic; N-methyl-D-aspartate; clozapine; psychosis; schizophrenia ID NEGATIVE SYMPTOMS; NMDA-ANTAGONIST; SCHIZOPHRENIA; HALOPERIDOL; PREDICTORS; RECEPTOR; GLYCINE; TRIAL AB Several lines of evidence suggest that the glutamatergic N-methyl-D-aspartate (NMDA) receptor is involved in the antipsychotic efficacy of the atypical antipsychotic agent clozapine. Clinical data on the interaction between clozapine's mechanism of action and NMDA receptor function have been lacking secondary to a paucity of pharmacologic probes of the NMDA system. We have utilized a double-blind, placebo-controlled infusion paradigm with subanesthetic doses of the NMDA antagonist ketamine to test the hypothesis that clozapine would blunt ketamine-induced psychotic symptoms in schizophrenic patients. Ten schizophrenic patients underwent ketamine infusions while antipsychotic drug free and also during treatment with clozapine. Antipsychotic drug-free patients experienced increases in ratings of positive and negative symptoms. Clozapine treatment significantly blunted the ketamine-induced increase in positive symptoms. These data suggest that NMDA receptor function may be involved in the unique antipsychotic efficacy of clozapine. Published 1997 by Society of Biological Psychiatry. RP Malhotra, AK (reprint author), NIMH,EXPT THERAPEUT BRANCH,NIH,BLDG 10,ROOM 4N212,10 CTR DR,BETHESDA,MD 20892, USA. NR 26 TC 138 Z9 138 U1 0 U2 1 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 OCT 15 PY 1997 VL 42 IS 8 BP 664 EP 668 DI 10.1016/S0006-3223(96)00546-X PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA XY248 UT WOS:A1997XY24800004 PM 9325559 ER PT J AU Funakoshi, S Hirano, A Beckwith, M Asai, O Jorgensen, G Tian, ZG Hornick, JL Hu, PS Khawli, LA Epstein, AL Longo, DL Murphy, WJ AF Funakoshi, S Hirano, A Beckwith, M Asai, O Jorgensen, G Tian, ZG Hornick, JL Hu, PS Khawli, LA Epstein, AL Longo, DL Murphy, WJ TI Antitumor effects of nonconjugated murine Lym-2 and human-mouse chimeric CLL-1 monoclonal antibodies against various human lymphoma cell lines in vitro and in vivo SO BLOOD LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; MEDIATED GROWTH-INHIBITION; ANTI-IDIOTYPE ANTIBODIES; B-LYMPHOCYTES; MICE; RADIOIMMUNOCONJUGATE; MALIGNANCIES; ACTIVATION; APOPTOSIS; TUMORS AB Lym-2 is a murine monoclonal antibody (MoAb) directed towards a human class II molecule variant reactive with both normal and neoplastic human B lymphocytes. Previous studies have shown that signals transmitted by class II molecules that stimulate normal lymphocytes can be inhibitory for B-cell lymphoma growth by signaling activation-induced cell death. Therefore, we sought to evaluate the effects of nonconjugated murine Lym-2 and a human-mouse chimeric Lym-2 (chCLL-1; with murine variable regions and human constant regions) MoAb on the growth of various human lymphomas by using both in vitro and in vivo assays. Cell lines derived from Burkitt's lymphomas, diffuse large cell B-cell lymphomas, anaplastic large-cell lymphomas, and Epstein-Parr virus-induced B-cell lymphomas were incubated with Lym-2 or chCLL-1 in vitro, and effects on proliferation were determined by [H-3]-thymidine incorporation. The effects of Lym-2 in vitro were also compared with those of Lym-1, which is a similar MoAb that has been evaluated clinically. After immobilization, which enhances crosslinking of the MoAbs, both Lym-2 and chCLL-1 were capable of directly inhibiting the growth of various lymphoma lines in vitro. These human lymphomas were then transferred into mice with severe combined immunodeficiency to evaluate the efficacy of these MoAbs in vivo. Treatment with either murine Lym-2 or the chimeric chCLL-1 were significantly effective in improving the survival of tumor-bearing mice. These results indicate that stimulation by nonconjugated chCLL-1 may offer a biological approach to the treatment of various human lymphomas. This is a US government work. There are no restrictions on its use. C1 NCI,LAB LEUKOCYTE BIOL,DIV BASIC SCI,INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,FREDERICK,MD 21702. NIA,BALTIMORE,MD 21224. UNIV SO CALIF,SCH MED,DEPT PATHOL,LOS ANGELES,CA 90033. RI Tian, Zhigang/J-3512-2013 NR 23 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 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 1997 VL 90 IS 8 BP 3160 EP 3166 PG 7 WC Hematology SC Hematology GA YC736 UT WOS:A1997YC73600032 PM 9376598 ER PT J AU Woodhouse, EC Chuaqui, RF Liotta, LA AF Woodhouse, EC Chuaqui, RF Liotta, LA TI General mechanisms of metastasis SO CANCER LA English DT Article; Proceedings Paper CT Symposium on Skeletal Complications of Malignancy CY APR 19-20, 1997 CL NIH, NATCHER CTR, BETHESDA, MD SP Paget Fdn HO NIH, NATCHER CTR DE cancer; metastasis; angiogenesis; invasion; osteolysis; osteosclerosis; chemotaxis; growth factor ID HORMONE-RELATED PROTEIN; HEPATOCYTE GROWTH-FACTOR; TUMOR-CELL INVASION; MOTILITY-STIMULATING PROTEIN; BREAST-CANCER METASTASES; HUMAN CUTANEOUS MELANOMA; EXTRACELLULAR-MATRIX; TISSUE INHIBITOR; AUTOCRINE GROWTH; IV COLLAGENASE AB In the present article, the steps involved in the process of tumor metastasis are discussed. Several events are required for malignant cells to leave the primary tumor and proliferate at a distant site: vessel formation (angiogenesis), cell attachment, invasion (matrix degradation, cell motility), and cell proliferation. Molecular mechanisms underlying each of these steps are described. Based on blocking these processes, new anti-metastasis therapies are being developed. (C) 1997 American Cancer Society. RP Woodhouse, EC (reprint author), NCI,PATHOL LAB,DIV CLIN SCI,NIH,9000 ROCKVILLE PIKE,BLDG 10,ROOM 2A33,BETHESDA,MD 20892, USA. NR 117 TC 566 Z9 592 U1 3 U2 32 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 OCT 15 PY 1997 VL 80 IS 8 SU S BP 1529 EP 1537 DI 10.1002/(SICI)1097-0142(19971015)80:8+<1529::AID-CNCR2>3.3.CO;2-# PG 9 WC Oncology SC Oncology GA YA765 UT WOS:A1997YA76500003 PM 9362419 ER PT J AU Isogai, M Chiantore, MV Haque, M Scita, G De Luca, LM AF Isogai, M Chiantore, MV Haque, M Scita, G De Luca, LM TI Expression of a dominant-negative retinoic acid receptor construct reduces retinoic acid metabolism and retinoic acid-induced inhibition of NIH-3T3 cell growth SO CANCER RESEARCH LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; 2ND PRIMARY TUMORS; TISSUE TRANSGLUTAMINASE; RAR-ALPHA; DIFFERENTIATION; CARCINOMA; IDENTIFICATION; PREVENTION; BINDING AB We have previously reported an unexpected relationship between retinoic acid-induced inhibition of cell growth and the ability of various cell lines to metabolize the retinoid, Here, we report that stable expression of the truncated retinoic acid receptor RAR alpha 403, transduced in NIH-3T3 cells by a retroviral vector, rendered the cells resistant to retinoic acid for growth inhibition and reduced their ability to metabolize the retinoid at the same time as it blunted the induction of the target gene transglutaminase II, The data suggest that retinoic acid receptors mediate the growth-inhibitory action of retinoic acid as well as its metabolism and the induction of transglutaminase II. C1 NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, NIH, BETHESDA, MD 20892 USA. RI Scita, GIORGIO/J-9670-2012; OI Scita, Giorgio/0000-0001-7984-1889 NR 24 TC 14 Z9 14 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 1997 VL 57 IS 20 BP 4460 EP 4464 PG 5 WC Oncology SC Oncology GA YA360 UT WOS:A1997YA36000005 PM 9377552 ER PT J AU Kitaeva, MN Grogan, L Williams, JP Dimond, E Nakahara, K Hausner, P DeNobile, JW Soballe, PW Kirsh, IR AF Kitaeva, MN Grogan, L Williams, JP Dimond, E Nakahara, K Hausner, P DeNobile, JW Soballe, PW Kirsh, IR TI Mutations in beta-catenin are uncommon in colorectal cancer occurring in occasional replication error-positive tumors SO CANCER RESEARCH LA English DT Article ID TRANSCRIPTION FACTOR LEF-1; CELL-LINES; MICROSATELLITE INSTABILITY; SUPPRESSOR PROTEIN AB beta-Catenin has been identified as an oncogene in colon cancer and melanoma, Phosphorylation of sites in exon 3 of beta-catenin leads to degradation of this protein. These sites are primary targets for activating mutations. The frequency with which oncogenic mutations at these sites are found in colorectal cancer is unknown, as is the frequency of their occurrence in other malignancies, We analyzed 92 colorectal cancers (CRCs) and 57 cancer cell lines (representing a diversity of tumor types) to determine the frequency of activating mutations in this gene, Mutations in exon 3 of beta-catenin were found in 2 of 92 CRCs and in the colorectal cancer cell line HCT 116. Both tumors with beta-catenin mutations exhibited widespread microsatellite instability, which is indicative of a replication error phenotype, a phenotype known to be present in HCT 116. This suggests that mutations in beta-catenin are infrequent in CRC and miscellaneous cancer cell lines and may occur in association with a replication error phenotype. C1 NATL NAVAL MED CTR, DEPT PATHOL, BETHESDA, MD 20889 USA. NATL NAVAL MED CTR, DEPT SURG, BETHESDA, MD 20889 USA. UNIFORMED SERV UNIV HLTH SCI, DEPT MED, BETHESDA, MD 20889 USA. UNIFORMED SERV UNIV HLTH SCI, DEPT SURG, BETHESDA, MD 20889 USA. RP Kitaeva, MN (reprint author), NCI, DEPT GENET,MED BRANCH,DIV CLIN SCI,BLDG 8, ROOM 5105, BETHESDA, MD 20889 USA. NR 22 TC 123 Z9 126 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 1997 VL 57 IS 20 BP 4478 EP 4481 PG 4 WC Oncology SC Oncology GA YA360 UT WOS:A1997YA36000009 PM 9377556 ER PT J AU Nitiss, JL Pourquier, P Pommier, Y AF Nitiss, JL Pourquier, P Pommier, Y TI Aclacinomycin A stabilizes topoisomerase I covalent complexes SO CANCER RESEARCH LA English DT Article ID MEDIATED DNA CLEAVAGE; CELL LUNG-CANCER; BREAKAGE-REUNION REACTION; ANTITUMOR DRUGS; INTOPLICINE RP-60475; INDUCED CYTOTOXICITY; ACTINOMYCIN-D; CAMPTOTHECIN; INHIBITORS; ETOPOSIDE AB Aclacinomycin A (aclarubicin) is an anthracycline anticancer agent with demonstrated activity against both leukemias and solid tumors, Previous results suggested that a major activity of aclacinomycin A is the inhibition of topoisomerase II catalytic activity, We have applied a yeast system to test whether aclacinomycin A is a topoisomerase II inhibitor in vivo and to test whether we could identify other important targets of this drug, We have found that overexpression of yeast topoisomerase II confers resistance to aclacinomycin A in yeast, consistent with the hypothesis that this drug is a catalytic inhibitor of topoisomerase II, Interestingly, we have also found that in yeast, aclacinomycin A, like camptothecin, stabilizes topoisomerase I cleavage, We carried out biochemical analysis with purified human topoisomerase I and demonstrated that this drug efficiently stabilizes topoisomerase I covalent complexes, indicating that aclacinomycin A represents a novel class of combined topoisomerase I/II inhibitor. C1 NCI, MOL PHARMACOL LAB, DIV BASIC SCI, BETHESDA, MD 20892 USA. RP Nitiss, JL (reprint author), ST JUDE CHILDRENS RES HOSP, DEPT MOL PHARMACOL, 332 N LAUDERDALE ST, MEMPHIS, TN 38105 USA. RI Nitiss, John/E-9974-2010; OI Nitiss, John/0000-0002-1013-4972 FU NCI NIH HHS [CA21765, CA52814] NR 59 TC 55 Z9 56 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 1997 VL 57 IS 20 BP 4564 EP 4569 PG 6 WC Oncology SC Oncology GA YA360 UT WOS:A1997YA36000023 PM 9377570 ER PT J AU Zaremba, S Barzaga, E Zhu, MZ Soares, N Tsang, KY Schlom, J AF Zaremba, S Barzaga, E Zhu, MZ Soares, N Tsang, KY Schlom, J TI Identification of an enhancer agonist cytotoxic T lymphocyte peptide from human carcinoembryonic antigen SO CANCER RESEARCH LA English DT Article ID CELL RECEPTOR ANTAGONISTS; HUMAN-MELANOMA; CANCER-PATIENTS; EPITOPES; LIGANDS; COMPLEXES; RESPONSES; VACCINE; TUMOR; CEA AB A vaccination strategy designed to enhance the immunogenicity of self-antigens that are overexpressed in tumor cells is to identify and slightly modify immunodominant epitopes that elicit T-cell responses. The resultant T cells, however, must maintain their ability to recognize the native configuration of the peptide-MHC interaction on the tumor cell target. We used a strategy to enhance the immunogenicity of a human CTL epitope directed against a human self-antigen, which involved the modification of individual amino acid residues predicted to interact with the T-cell receptor; this strategy, moreover, required no prior knowledge of these actual specific interactions, Single amino acid substitutions were introduced to the CAP1 peptide (YLSGANLNL), an immunogenic HLA-A2(+)-binding peptide derived from human carcinoembryonic antigen (CEA). In this study, four amino acid residues that were predicted to potentially interact with the T-cell receptor of CAP1-specific CTLs were systematically replaced, Analogues were tested for binding to HLA-A2 and for recognition by an established CTL line directed against CAP1, This line was obtained from peripheral blood mononuclear cells from an HLA-A2(+) individual vaccinated with a vaccinia-CEA recombinant. An analogue peptide was identified that was capable of sensitizing CAP1-specific CTLs 10(2)-10(3) times more efficiently than the native CAP1 peptide, This enhanced recognition was shown not to be due to better binding to HLA-A2. Therefore, the analogue CAP1-6D (YLSGADLNL, Asn at position 6 replaced by Asp) meets the criteria of a CTL enhancer agonist peptide. Both the CAP1-6D and the native CAP1 peptide were compared for the ability to generate specific CTL lines in vitro from unimmunized apparently healthy HLA-A2(+) donors, Whereas CAP1 failed to generate CTLs from normal peripheral blood mononuclear cells, the agonist peptide was able to generate CD8(+) CTL lines that recognized both the agonist and the native CAP1 sequence, Most importantly, these CTLs were capable of lysing human tumor cells endogenously expressing CEA, The use of enhancer agonist CTL peptides may thus represent a new efficient direction for immunotherapy protocols. C1 NCI,TUMOR IMMUNOL & BIOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 51 TC 160 Z9 168 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 1997 VL 57 IS 20 BP 4570 EP 4577 PG 8 WC Oncology SC Oncology GA YA360 UT WOS:A1997YA36000024 PM 9377571 ER PT J AU Coleman, AE Schrock, E Weaver, Z duManoir, S Yang, FT FergusonSmith, MA Ried, T Janz, S AF Coleman, AE Schrock, E Weaver, Z duManoir, S Yang, FT FergusonSmith, MA Ried, T Janz, S TI Previously hidden chromosome aberrations in T(12;15)-positive BALB/c plasmacytomas uncovered by multicolor spectral karyotyping SO CANCER RESEARCH LA English DT Article ID HEAVY-CHAIN LOCUS; ALKANE PRISTANE 2,6,10,14-TETRAMETHYLPENTADECANE; C-MYC RECOMBINATIONS; MURINE PLASMACYTOMAS; MOUSE PLASMACYTOMA; CELL-LINE; ABERRANT REARRANGEMENT; NEOPLASTIC DEVELOPMENT; RECIPROCAL EXCHANGE; MLL GENE AB The majority of BALB/c mouse plasmacytomas harbor a balanced T(12;15) chromosomal translocation deregulating the expression of the proto-oncogene c-myc. Recent evidence suggests that the T(12;15) is an initiating tumorigenic mutation that occurs in early plasmacytoma precursor cells. However, the possible contribution of additional chromosomal aberrations to the progression of plasmacytoma development has been largely ignored, Here we use multicolor spectral karyotyping (SKY) to evaluate 10 established BALB/c plasmacytomas in which the T(12;15) had been previously detected by G banding, SKY readily confirmed the presence of this translocation in all of these tumors and in three plasmacytomas newly identified secondary cytogenetic changes of the c-myc-deregulating chromosome (Chr) T(12;15). In addition, numerous previously unknown aberrations were found to be scattered throughout the genome, which was interpreted to reflect the general genomic instability of plasmacytomas, instability of this sort was not uniform, however, because only half of the tumors were heavily rearranged, Seven apparent hot spots of chromosomal rearrangements (40% incidence) were identified and mapped to Chrs 1B, 1G-H, 2G-H1, 4C7-D2, 12D, 14C-D2, and XE-F1. Two of these regions, Chr 1B and Chr 4C7-D2, are suspected to harbor plasmacytoma susceptibility loci; Pctr(1) and Pctr(2) on Chr 4C7-D2 and as yet unnamed loci on Chr 1B, These results suggest that secondary chromosomal rearrangements contribute to plasmacytoma progression in BALB/c mice. To evaluate the biological significance of these rearrangements, SKY will be used in follow-up experiments to search for the presence of recurrent and/or consistent secondary cytogenetic aberrations in primary BALB/c plasmacytomas. C1 NCI,GENET LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NIH,GENOME TECHNOL BRANCH,NATL HUMAN GENOME RES INST,BETHESDA,MD 20892. UNIV CAMBRIDGE,DEPT PATHOL,CAMBRIDGE CB2 1QP,ENGLAND. NR 53 TC 30 Z9 30 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 1997 VL 57 IS 20 BP 4585 EP 4592 PG 8 WC Oncology SC Oncology GA YA360 UT WOS:A1997YA36000026 PM 9377573 ER PT J AU Moriwaki, SI Tarone, RE Tucker, MA Goldstein, AM Kraemer, KH AF Moriwaki, SI Tarone, RE Tucker, MA Goldstein, AM Kraemer, KH TI Hypermutability of UV-treated plasmids in dysplastic nevus/familial melanoma cell lines SO CANCER RESEARCH LA English DT Article ID CUTANEOUS MALIGNANT-MELANOMA; SHUTTLE VECTOR PLASMID; XERODERMA-PIGMENTOSUM-CELLS; NEVUS SYNDROME; DNA-REPAIR; FAMILIAL MELANOMA; ESCHERICHIA-COLI; ULTRAVIOLET HYPERMUTABILITY; INDUCED MUTATIONS; TRICHOTHIODYSTROPHY CELLS AB Members of cutaneous melanoma (CM) families with dysplastic nevi (DN) are at high risk of developing CM. Using a shuttle vector plasmid, pSP189, cell lints from three patients with CM plus DN were previously found to have elevated post-UV plasmid mutability, To investigate familial occurrence of this cellular phenotype, we examined post-UV plasmid mutability in 31 lymphoblastoid cell lines from 6 familial CM kindreds. In comparison to 16 normal control lines, we found an abnormally elevated post-UV plasmid mutability in cell lines from 13 of 13 patients with CM plus DN (P = 1.5 x 10(-8)) and from 5 of 8 patients with DN only (P = 0.001), Elevated spontaneous plasmid mutation frequency (MF) was also present in cell lines from six of the CM plus DN patients (P = 0.002) and three of the DN-only patients (P = 0.028), However, cell lines from two patients with CM without DN had normal post-UV plasmid MF, Although not specific for CM patients, of 27 cell lines with elevated post-UV plasmid MF, only 8 were from donors who did not have CM + DN or DN (19 of 24 versus 8 of 28; P = 0.0003), This study indicates that post-UV plasmid hypermutability is a laboratory marker for members of melanoma-prone families and suggests that patients with familial CM have a defective mechanism for handling UV-induced DNA damage. C1 NCI,MOL CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. NCI,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. RI Tucker, Margaret/B-4297-2015 FU Intramural NIH HHS [Z01 BC004517-31] NR 53 TC 16 Z9 16 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 1997 VL 57 IS 20 BP 4637 EP 4641 PG 5 WC Oncology SC Oncology GA YA360 UT WOS:A1997YA36000033 PM 9377580 ER PT J AU Borowitz, MJ Bray, R Gascoyne, R Melnick, S Parker, JW Picker, L StatlerStevenson, M AF Borowitz, MJ Bray, R Gascoyne, R Melnick, S Parker, JW Picker, L StatlerStevenson, M TI US-Canadian consensus recommendations on the immunophenotypic analysis of hematologic neoplasia by flow cytometry: Data analysis and interpretation SO CYTOMETRY LA English DT Article; Proceedings Paper CT US/Canadian Consensus Conference Recommendations on the Immunophenotypic Analysis of Hematologic Neoplasia by Flow Cytometry CY NOV 16-17, 1995 CL BETHESDA, MD ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; MINIMAL RESIDUAL DISEASE; NON-HODGKINS-LYMPHOMA; HAIRY-CELL LEUKEMIA; ACUTE MYELOBLASTIC-LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; ACUTE MYELOCYTIC-LEUKEMIA; HUMAN BONE-MARROW C1 PATHOL EMORY REFERENCE LAB, ATLANTA, GA USA. BRITISH COLUMBIA CANC AGCY, DEPT PATHOL, VANCOUVER, BC V5Z 4E6, CANADA. MIAMI CHILDRENS HOSP, DEPT PATHOL, MIAMI, FL USA. UNIV SO CALIF, SCH MED, DEPT PATHOL, LOS ANGELES, CA 90033 USA. UNIV TEXAS, SW MED CTR, DEPT PATHOL, DALLAS, TX USA. NCI, PATHOL LAB, NIH, BETHESDA, MD 20892 USA. RP Borowitz, MJ (reprint author), JOHNS HOPKINS MED INST, DEPT PATHOL, 600 N WOLFE ST, BALTIMORE, MD 21287 USA. NR 115 TC 99 Z9 109 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-4763 J9 CYTOMETRY JI Cytometry PD OCT 15 PY 1997 VL 30 IS 5 BP 236 EP 244 DI 10.1002/(SICI)1097-0320(19971015)30:5<236::AID-CYTO4>3.0.CO;2-F PG 9 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YF220 UT WOS:A1997YF22000004 PM 9383097 ER PT J AU Raeber, AJ Race, RE Brandner, S Priola, SA Sailer, A Bessen, RA Mucke, L Manson, J Aguzzi, A Oldstone, MBA Weissmann, C Chesebro, B AF Raeber, AJ Race, RE Brandner, S Priola, SA Sailer, A Bessen, RA Mucke, L Manson, J Aguzzi, A Oldstone, MBA Weissmann, C Chesebro, B TI Astrocyte-specific expression of hamster prion protein (PrP) renders PrP knockout mice susceptible to hamster scrapie SO EMBO JOURNAL LA English DT Article DE astrocytes; hamster scrapie prions; PrP; transgenic mice ID FOLLICULAR DENDRITIC CELLS; CREUTZFELDT-JAKOB-DISEASE; TRANSGENIC MICE; MESSENGER-RNA; NEUROBLASTOMA-CELLS; INFECTED MICE; RESISTANT PRP; GENE; ACTIVATION; TISSUES AB Transmissible spongiform encephalopathies are characterized by spongiosis, astrocytosis and accumulation of PrPSc, an isoform of the normal host protein PrPC. The exact cell types responsible for agent propagation and pathogenesis are still uncertain. To determine the possible role of astrocytes, we generated mice devoid of murine PrP but expressing hamster PrP transgenes driven by the astrocyte-specific GFAP promoter. After inoculation with hamster scrapie, these mice accumulated infectivity and PrPSc to high levels, developed severe disease after 227 +/- 5 days and died 7 +/- 4 days later. Therefore, astrocytes could play an important role in scrapie pathogenesis, possibly by an indirect toxic effect on neurons. Interestingly, mice expressing the same transgenes but also endogenous murine PrP genes propagated infectivity without developing disease. C1 UNIV ZURICH, INST MOL BIOL, ABT 1, CH-8093 ZURICH, SWITZERLAND. NIAID, ROCKY MT LABS, PERSISTENT VIRAL DIS LAB, HAMILTON, MT 59840 USA. UNIV ZURICH HOSP, INST NEUROPATHOL, CH-8091 ZURICH, SWITZERLAND. Scripps Res Inst, DEPT NEUROPHARMACOL, DIV VIROL, LA JOLLA, CA 92037 USA. AFRC, INST ANIM HLTH, EDINBURGH, MIDLOTHIAN, SCOTLAND. RI Aguzzi, Adriano/A-3351-2008; Brandner, Sebastian/J-4562-2014; OI Brandner, Sebastian/0000-0002-9821-0342; Aguzzi, Adriano/0000-0002-0344-6708 FU NIA NIH HHS [AG04342] NR 59 TC 153 Z9 155 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD OCT 15 PY 1997 VL 16 IS 20 BP 6057 EP 6065 DI 10.1093/emboj/16.20.6057 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YD753 UT WOS:A1997YD75300001 PM 9321385 ER PT J AU Weber, IT Wu, J Adomat, J Harrison, RW Kimmel, AR Wondrak, EM Louis, JM AF Weber, IT Wu, J Adomat, J Harrison, RW Kimmel, AR Wondrak, EM Louis, JM TI Crystallographic analysis of human immunodeficiency virus 1 protease with an analog of the conserved CA-p2 substrate - Interactions with frequently occurring glutamic acid residue at P2' position of substrates SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE human immunodeficiency virus protease; crystal structure; proton-mediated interaction; viral maturation ID HIV-1 PROTEASE; CRYSTAL-STRUCTURE; CLEAVAGE SITES; ACTIVE-SITE; INHIBITOR; COMPLEX; TYPE-1; PROTEINASES; GAG; POLYPROTEINS AB Human immunodeficiency virus type 1 (HIV-1) protease hydrolysis of the Gag CA-p2 cleavage site is crucial for virion maturation and is optimal at acidic pH. To understand the processing of the CA-p2 site, we have determined the structure of HIV-1 protease complexed with an analog of the CA-p2 site, the reduced peptide inhibitor Arg-Val-Leu-r-Phe-Glu-Ala-Ahx-NH2 [r denotes the reduced peptide bond and Ahx 2-aminohexanoic acid (norleucine), respectively]. The crystal structure was refined to an R-factor of 0.17 at 0.21-nm resolution. The crystals have nearly the same lattice as related complexes in P2(1)2(1)2(1) which have twofold disordered inhibitor, but are in space group P2(1), and the asymmetric unit contains two dimers of HIV-1 protease related by 180 degrees rotation. An approximate non-crystallographic symmetry has replaced the exact crystal symmetry resulting in well-ordered inhibitor structure. Each protease dimer binds one ordered inhibitor molecule, but in opposite orientations. The interactions of the inhibitor with the two dimers are very similar for the central P2 Val to P2' Glu residues, but show more variation for the distal P3 Arg and P4' Ahx residues. Importantly, the carboxylate oxygens of Glu at P2' in the inhibitor are within hydrogen-bonding distance of a carboxylate oxygen of Asp30 of the protease suggesting that the two side chains share a proton. This interaction suggests that the enzyme-substrate complex is additionally stabilized at lower pH. The importance of this interaction is emphasized by the absence of polymorphisms of Asp30 in the protease and variants of P2' Glu in the critical CA-p2 cleavage site. C1 NIDDKD, CELLULAR & DEV BIOL LAB, MOL MECHANISMS DEV SECT, NIH, BETHESDA, MD 20892 USA. RP Weber, IT (reprint author), THOMAS JEFFERSON UNIV, KIMMEL CANC CTR, DEPT MICROBIOL & IMMUNOL, PHILADELPHIA, PA 19107 USA. FU NCI NIH HHS [CA58166] NR 30 TC 37 Z9 38 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD OCT 15 PY 1997 VL 249 IS 2 BP 523 EP 530 DI 10.1111/j.1432-1033.1997.00523.x PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YC461 UT WOS:A1997YC46100024 PM 9370363 ER PT J AU Pooler, MR Hartung, JS Fenton, RG AF Pooler, MR Hartung, JS Fenton, RG TI Sequence analysis of a 1296-nucleotide plasmid from Xylella fastidiosa SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE Xylella fastidiosa; plasmid sequence; Pierce's disease; leaf scorch; DNA homology; cryptic plasmid ID PSEUDOMONAS-AERUGINOSA 7NSK2; CITRUS VARIEGATED CHLOROSIS; LEAF SCORCH; INHABITING BACTERIA; AXENIC CULTURE; PATHOGENICITY; DISEASE; STRAINS; ASSOCIATION; PLANTS AB A cryptic plasmid from Xylella fastidiosa strain ATCC 35868 was cloned, sequenced, and the sequence entered into GenBank (U71220). The plasmid is 1296 nucleotides in length with 55% GC content and three open reading frames. A plasmid with sequence homology was found in only one other strain of X. fastidiosa, ATCC 35878, Searches of the GenBank reveal nucleotide sequence homology with plasmid pNKH43 from Stenotrophomonas maltophilia, and amino acid sequence homology with phage Pf3 from Pseudomonas aeruginosa, plasmid pAP12875 from Acetobacter pasteurianus, and plasmid pVT736-1 from Actinobacillus actinomycetemcomitans. C1 USDA ARS, Beltsville Agr Res Ctr, Beltsville Agr Res Ctr W, Beltsville, MD 20705 USA. NCI, Frederick Canc Res & Dev Ctr, Div Clin Sci, Navy Med Oncol Branch, Frederick, MD 21701 USA. RP Pooler, MR (reprint author), US Natl Arboretum, 3501 New York Ave NE, Washington, DC 20002 USA. EM mpooler@ars-grin.gov NR 24 TC 12 Z9 13 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD OCT 15 PY 1997 VL 155 IS 2 BP 217 EP 222 DI 10.1111/j.1574-6968.1997.tb13881.x PG 6 WC Microbiology SC Microbiology GA YY672 UT WOS:000072172100013 PM 9351204 ER PT J AU Otterson, GA Kaye, FJ AF Otterson, GA Kaye, FJ TI A 'core ATPase', Hsp70-like structure is conserved in human, rat, and C-elegans STCH proteins SO GENE LA English DT Article DE ionophore A23187; cloning; heat shock; protein chaperone; phylogram ID HEAT-SHOCK; NUCLEOTIDE-SEQUENCE; CHAPERONES; CYCLE; CELL AB We have identified the rat and Caenorhabditis elegans homologues of a 'core ATPase'-encoding Hsp70-like gene, designated Stch. We observed that the human, rat, and C. elegans Stch genes have conserved a stop codon immediately distal to the sequence encoding the Hsp70 ATPase domain. This results in the functional equivalent of an N-terminal, proteolytically cleaved fragment of Hsc70/BiP. Each homologue contains a hydrophobic signal sequence, demonstrates striking identity within the Hsp70 ATPase domain, and retains a similar C-terminal sequence (STCH specific cluster III) that is unique among Hsp70 proteins and which truncates the peptide binding domain. In addition, we have identified an internal 35-aa region that is homologous to the minimal sequence of the Hip chaperone co-factor that is required for direct binding to the ATPase domain of Hsp70. Adjacent to this region, the rat and human STCH protein sequences diverge within a short internal 'insertion' sequence that interrupts the ATPase subdomain between the phosphate-2 and adenosine ATP-binding sites. We have also demonstrated that both human and rat Stch are constitutively produced and are induced by the calcium ionophore A23187, but not by heat shock. The recognition that the truncated 'core ATPase' structure of the STCH molecule is conserved in human, rat, and C. elegans tissues suggests an important role for this unique member of the membrane-bound Hsp70 family. (C) 1997 Elsevier Science B.V. C1 USN HOSP,DEPT GENET,MED BRANCH,DIV CLIN SCI,NCI,BETHESDA,MD 20889. RI kaye, frederic/E-2437-2011 NR 20 TC 12 Z9 14 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD OCT 15 PY 1997 VL 199 IS 1-2 BP 287 EP 292 DI 10.1016/S0378-1119(97)00383-1 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA YB732 UT WOS:A1997YB73200036 PM 9358068 ER PT J AU Jensen, MR Factor, VM Zimonjic, DB Miller, MJ Keck, CL Thorgeirsson, SS AF Jensen, MR Factor, VM Zimonjic, DB Miller, MJ Keck, CL Thorgeirsson, SS TI Chromosome localization and structure of the murine cyclin G1 gene promoter sequence SO GENOMICS LA English DT Article ID MUSCLE DIFFERENTIATION; SPLICE SITES; DNA-DAMAGE; P53; EXPRESSION; HOMOLOGY; CELLS; INHIBITORS; INDUCTION; PROTEIN AB Cyclins play an essential role in the control of the cell cycle. In this study the murine cyclin G1 gene expression, structure, and chromosomal localization were examined. Genes with high homology to murine cyclin G1 were detected in various mammals, including human, monkey, rat, dog, cow, and rabbit, but not in yeast or chicken, Cyclin G1 gene was expressed in all murine tissues examined, with the highest levels in cardiac and skeletal muscle. A 10,366-bp genomic DNA fragment encompassing the promoter region and the 5'-flanking region of the gene was cloned and sequenced. Three putative binding sites for the myocyte enhancer factor-a family of transcription factors were revealed. Furthermore, an upstream p53-binding site was localized to nucleotides -252 to -233 and a:new putative p53-binding site was identified in the first intronic region at nucleotides 275 to 294. By fluorescence in situ hybridization, the cyclin G1 gene was mapped to mouse chromosome 11B1.1. This region is homologous with human chromosome 5q31-q32, consistent with the recent mapping of the human cyclin G1 gene to chromosome 5q32-q34. Localization of murine cyclin G1 will facilitate determination of gene linkage and the identification of synteny groups in mammals and of DNA elements in or near this gene that mediate its tissue expression or development-specific pattern Of expression. (C) 1997 Academic Press. C1 NCI,EXPT CARCINOGENESIS LAB,DIV BASIC SCI,BETHESDA,MD 20892. RI Jensen, Michael/E-9677-2011 NR 39 TC 12 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD OCT 15 PY 1997 VL 45 IS 2 BP 297 EP 303 DI 10.1006/geno.1997.4947 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA YC792 UT WOS:A1997YC79200009 PM 9344652 ER PT J AU Fletcher, CF Okano, HJ Gilbert, DJ Yang, Y Yang, CW Copeland, NG Jenkins, NA Darnell, RB AF Fletcher, CF Okano, HJ Gilbert, DJ Yang, Y Yang, CW Copeland, NG Jenkins, NA Darnell, RB TI Mouse chromosomal locations of nine genes encoding homologs of human paraneoplastic neurologic disorder antigens SO GENOMICS LA English DT Article ID RNA-BINDING PROTEIN; STIFF-MAN SYNDROME; LINKAGE MAP; CEREBELLAR DEGENERATION; ENCEPHALOMYELITIS ANTIGEN; INTERSPECIFIC BACKCROSS; MOLECULAR-CLONING; DNA-BINDING; LOCALIZATION; EXPRESSION AB The paraneoplastic neurologic disorders (PND) are a rare group of neurologic syndromes that arise when an immune response to systemic tumors expressing neuronal proteins (''onconeural antigens'') develops into an autoimmune neuronal degeneration. The use of patient antisera to clone the genes encoding PND antigens has led to new insight into the mechanism of these autoimmune disorders. The tumor antigens can now be grouped into three classes: (1) neuron-specific RNA-binding proteins, (2) nerve terminal vesicle-associated proteins, and (3) cytoplasmic signaling proteins. To understand better the evolutionary relatedness of these genes and to evaluate them as candidates for inherited neurological disorders, we have determined the mouse chromosomal locations of nine of these genes-Hua, Hub, Hue, Hud, Nova1, Nova2, Natpb, Cdr2, and Cdr3. These data suggest that the Hua-Hud genes arose from gene duplication and dispersion, while the other genes are dispersed in the genome. We also predict the chromosomal locations of these genes in human and discuss the potential of these genes as candidates for uncloned mouse and human mutations. (C) 1997 Academic Press. C1 ROCKEFELLER UNIV, MOL NEUROONCOL LAB, NEW YORK, NY 10021 USA. RP Fletcher, CF (reprint author), NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,POB B, BLDG 539, FREDERICK, MD 21702 USA. RI Darnell, Robert/B-9022-2008 OI Darnell, Robert/0000-0002-5134-8088 FU NCI NIH HHS [CA 09673-18]; NINDS NIH HHS [R01 NS34389] NR 59 TC 12 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD OCT 15 PY 1997 VL 45 IS 2 BP 313 EP 319 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA YC792 UT WOS:A1997YC79200011 PM 9344654 ER PT J AU Sladek, R Beatty, B Squire, J Copeland, NG Gilbert, DJ Jenkins, NA Giguere, V AF Sladek, R Beatty, B Squire, J Copeland, NG Gilbert, DJ Jenkins, NA Giguere, V TI Chromosomal mapping of the human and murine orphan receptors ERR alpha (ESRRA) and ERR beta (ESRRB) and identification of a novel human ERR alpha-related pseudogene SO GENOMICS LA English DT Article ID INSITU HYBRIDIZATION; NUCLEAR RECEPTORS; GENOME; LOCALIZATION; SUPERFAMILY; EXPRESSION; LINKAGE; CLONES; MEMBER; GENE AB The estrogen-related receptors ERR alpha and ERR beta (formerly ERR1 and ERRS) form a subgroup of the steroid/thyroid/retinoid receptor family. ERR alpha and ERR beta are homologous to the estrogen receptor and bind similar DNA targets; however, they are unable to activate gene transcription in response to estrogens. We have used interspecific backcross analysis to map the murine Estrra locus to chromosome 19 and Estrrb to mouse chromosome 12. Using fluorescence in situ hybridization, we have mapped the human ESRRA gene to chromosome 11q12-q13 and the human ESRRB gene to chromosome 14q24.3. In addition, we report the isolation of a processed human ERR alpha pseudogene mapping to chromosome 13q12.1. To our knowledge, this represents the first report of a pseudogene associated with a member of the nuclear receptor superfamily. (C) 1997 Academic Press. C1 ROYAL VICTORIA HOSP,MOL ONCOL GRP,MONTREAL,PQ H3A 1A1,CANADA. MCGILL UNIV,DEPT BIOCHEM,MONTREAL,PQ H3A 1A1,CANADA. MCGILL UNIV,DEPT MED,MONTREAL,PQ H3A 1A1,CANADA. MCGILL UNIV,DEPT ONCOL,MONTREAL,PQ H3A 1A1,CANADA. HOSP SICK CHILDREN,CGAT FISH,MAPPING RESOURCE CTR,TORONTO,ON M5G 1X8,CANADA. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. OI Squire, Jeremy/0000-0002-9863-468X NR 24 TC 21 Z9 21 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 0888-7543 J9 GENOMICS JI Genomics PD OCT 15 PY 1997 VL 45 IS 2 BP 320 EP 326 DI 10.1006/geno.1997.4939 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA YC792 UT WOS:A1997YC79200012 PM 9344655 ER PT J AU Hardiman, G Jenkins, NA Copeland, NG Gilbert, DJ Garcia, DK Naylor, SL Kastelein, RA Bazan, JF AF Hardiman, G Jenkins, NA Copeland, NG Gilbert, DJ Garcia, DK Naylor, SL Kastelein, RA Bazan, JF TI Genetic structure and chromosomal mapping of MyD88 SO GENOMICS LA English DT Article ID COLONY-STIMULATING FACTOR; IMMEDIATE EARLY RESPONSE; FACTOR TNF RECEPTOR; CELL LUNG-CANCER; TERMINAL DIFFERENTIATION; GENOMIC ORGANIZATION; LEUKEMIA-CELLS; MYELOID CELLS; DEATH DOMAIN; GROWTH AB The myeloid differentiation (MyD) marker MyD88 was initially characterized as a primary response gene, upregulated in mouse M1 myeloleukemic cells in response to differentiation induced by interleukin-6. Subsequent analysis revealed that MyD88 possesses a unique modular structure, which consists of an N-terminal ''death domain,'' similar to the intracellular segments of TNF receptor 1 and Fas, and a C-terminal region related to the cytoplasmic domains of the Drosophila morphogen Toll and vertebrate interleukin-l receptors. In this report we describe the cloning and gene structure of mouse MyD88. The complete coding sequence of mouse MyD88 spans five exons, with the first exon encoding the complete death domain. Zoo-blot analysis revealed that MyD88 is an evolutionarily conserved gene. MyD88 was localized to the distal region of mouse chromosome 9 by interspecific backcross mapping. The human homolog (hMyD88) was mapped to chromosome 3p22-p21.3 by PCR analysis of a human chromosome 3 somatic cell hybrid mapping panel. Northern blot analysis revealed widespread expression of MyD88 in many adult mouse tissues, and RT-PCR studies detected MyD88 mRNA in T and B cell lines and differentiating embryonic stem cells. The broad expression pattern demonstrates that mouse MyD88 expression is not restricted to cells of myeloid lineage as was originally believed. (C) 1997 Academic Press. C1 DNAX RES INST MOL & CELLULAR BIOL INC,DEPT MOL BIOL,PALO ALTO,CA 94304. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. UNIV TEXAS,HLTH SCI CTR,DEPT CELLULAR & STRUCT BIOL,SAN ANTONIO,TX 78284. RI Bazan, J. Fernando/B-4562-2010 NR 43 TC 25 Z9 33 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD OCT 15 PY 1997 VL 45 IS 2 BP 332 EP 339 DI 10.1006/geno.1997.4940 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA YC792 UT WOS:A1997YC79200014 PM 9344657 ER PT J AU Whitaker, TL Steinbrecher, KA Copeland, NG Gilbert, DJ Jenkins, NA Cohen, MB AF Whitaker, TL Steinbrecher, KA Copeland, NG Gilbert, DJ Jenkins, NA Cohen, MB TI The uroguanylin gene (Guca1b) is linked to guanylin (Guca2) on mouse chromosome 4 SO GENOMICS LA English DT Article ID HEAT-STABLE ENTEROTOXIN; DEPENDENT PROTEIN-KINASE; LINKAGE MAP; CELL LINE; EXPRESSION; INTESTINE; CYCLASE; PEPTIDE; TRANSCRIPTION; SEQUENCES AB Uroguanylin is an endogenous ligand of the intestinal receptor guanylate cyclase-C (GC-C). Both uroguanylin and the related peptide ligand guanylin bind to GC-C and stimulate an increase in cyclic GMP, inducing chloride secretion via the cystic fibrosis transmembrane conductance regulator. We describe the cloning of the complete mouse uroguanylin gene (Guca1b) and show that Guca1b is tightly linked to the mouse guanylin gene on chromosome 4. The two genes are structurally similar, being composed of three short exons; the uroguanylin gene spans 2.4 kb and the guanylin gene spans 1.7 kb. Uroguanylin mRNA is most prominent in proximal small intestine, whereas guanylin mRNA is predominantly expressed in distal small intestine and colon. The upstream promoter sequence of the mouse uroguanylin gene contains a canonical TATA element at the site of transcription initiation and consensus binding sites for several known transcription factors, including HNF-1 and Spl within the first 1 kb. Although the gene structure and coding sequences of uroguanylin and guanylin are similar, the 5' flanking sequences and patterns of expression of these two genes in the intestine are different. It is likely that uroguanylin and guanylin represent gene duplications that have evolved to allow overlapping and complementary patterns of expression in the intestine. (C) 1997 Academic Press. C1 CHILDRENS HOSP,MED CTR,DIV PEDIAT GASTROENTEROL & NUTR,CINCINNATI,OH 45229. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. OI Cohen, Mitchell/0000-0002-4412-350X FU NIDDK NIH HHS [DK 47318] NR 30 TC 14 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD OCT 15 PY 1997 VL 45 IS 2 BP 348 EP 354 DI 10.1006/geno.1997.4942 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA YC792 UT WOS:A1997YC79200016 PM 9344659 ER PT J AU Hunt, CR Goswami, PC Kozak, CA AF Hunt, CR Goswami, PC Kozak, CA TI Assignment of the mouse Hsp25 and Hsp105 genes to the distal region of chromosome 5 by linkage analysis SO GENOMICS LA English DT Article ID HEAT-SHOCK PROTEIN; EXPRESSION; CLONING C1 NIAID,MOL MICROBIOL LAB,BETHESDA,MD 20892. RP Hunt, CR (reprint author), WASHINGTON UNIV,SCH MED,DEPT RADIAT ONCOL,4511 FOREST PK BLVD,ST LOUIS,MO 63108, USA. FU NCI NIH HHS [CA 60757] NR 14 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD OCT 15 PY 1997 VL 45 IS 2 BP 462 EP 463 DI 10.1006/geno.1997.4973 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA YC792 UT WOS:A1997YC79200039 PM 9344682 ER PT J AU Brody, LC Biesecker, BB AF Brody, LC Biesecker, BB TI Breast cancer: The high-risk mutations SO HOSPITAL PRACTICE LA English DT Article ID BRCA1; CELLS AB Mutations in the two known BRCA genes account for only 5% to 10% of breast cancer, The genes may play a role in genomic stability; their role in sporadic cancer remains unknown, Hence, genetic testing has created clinical dilemmas, Some pertain to women whose family history suggests inherited risk. Others, including the false reassurance that may be conferred by a negative finding, apply throughout the general population. RP Brody, LC (reprint author), NATL HUMAN GENOME RES INST,LAB GENE TRANSFER,BETHESDA,MD, USA. NR 14 TC 1 Z9 1 U1 0 U2 1 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 SN 8750-2836 J9 HOSP PRACT JI Hosp. Pract. PD OCT 15 PY 1997 VL 32 IS 10 BP 59 EP & PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA YA732 UT WOS:A1997YA73200010 PM 9341636 ER PT J AU McKinnon, WC Baty, BJ Bennett, RL Magee, M NeufeldKaiser, WA Peters, KF Sawyer, JC Schneider, KA AF McKinnon, WC Baty, BJ Bennett, RL Magee, M NeufeldKaiser, WA Peters, KF Sawyer, JC Schneider, KA TI Predisposition genetic testing for late-onset disorders in adults - A position paper of the National Society of Genetic Counselors SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID HUNTINGTONS-DISEASE; COLORECTAL-CANCER; INFORMED CONSENT; OVARIAN-CANCER; FAMILY HISTORY; BRCA1; PROTOCOL; BREAST; SUSCEPTIBILITY; MODEL C1 UNIV VERMONT,COLL MED,DEPT PEDIAT,BURLINGTON,VT. UNIV UTAH,MED CTR,DEPT PEDIAT,SALT LAKE CITY,UT. UNIV WASHINGTON,DIV MED GENET,SEATTLE,WA 98195. UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,CTR HUMAN & MOL GENET,NEWARK,NJ 07103. ODESSA CHILDRENS CLIN,COMPREHENS SICKLE CELL PROGRAM,SEATTLE,WA. NIH,NATL CTR HUMAN GENOME RES,MED GENET BRANCH,BETHESDA,MD 20892. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT BEHAV SCI,HOUSTON,TX. DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. FU NCI NIH HHS [CA63681]; NCRR NIH HHS [RR00064]; NHGRI NIH HHS [HG00199] NR 60 TC 75 Z9 75 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 OCT 15 PY 1997 VL 278 IS 15 BP 1217 EP 1220 DI 10.1001/jama.278.15.1217 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA XZ709 UT WOS:A1997XZ70900002 PM 9333247 ER PT J AU Gronberg, H Isaacs, SD Smith, JR Carpten, JD Bova, GS Freije, D Xu, JF Meyers, DA Collins, FS Trent, JM Walsh, PC Isaacs, WB AF Gronberg, H Isaacs, SD Smith, JR Carpten, JD Bova, GS Freije, D Xu, JF Meyers, DA Collins, FS Trent, JM Walsh, PC Isaacs, WB TI Characteristics of prostate cancer in families potentially linked to the hereditary prostate cancer 1 (HPC1) locus SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID BREAST-CANCER; PATHOLOGICAL FEATURES; RISK; RELATIVES AB Context.-Approximately 9% of prostate cancer cases have been estimated to result from inheritance of mutated prostate cancer susceptibility genes. Few data exist as to whether there are clinical differences between prostate cancers that are inherited and those that occur in the general population. Objective.-To investigate phenotypic characteristics of families potentially linked to the hereditary prostate cancer 1 (HPC1) locus on chromosome 1q24-25. Design.-Retrospective case study in which clinical data were extracted from medical and pathological records. Families.-A total of 74 North American families with hereditary prostate cancer. Prostate cancer cases from the National Cancer Data Base were used as a reference population for comparison. Main Outcome Measures.-The families were divided into 2 groups: either potentially linked (33 families with 133 men with prostate cancer), and thus likely to be carrying an altered HPC1 gene, or potentially unlinked (41 families with 172 men with prostate cancer), on the basis of haplotype analysis in the region of HPC1, The age at diagnosis of prostate cancer, serum prostate-specific antigen levels, digital rectal examination status, stage, grade, primary treatment of prostate cancers, and occurrence of other cancers were compared between the groups. Results.-The mean age at diagnosis of prostate cancer for men in potentially linked families was significantly lower than for men in potentially unlinked families (63.7 vs 65.9 years, respectively, P=.01; mean age at diagnosis in the reference population was 71.6 years). Higher-grade cancers (grade 3) were more common in potentially linked families, and advanced-stage disease was found in 41% of the case patients in potentially linked families compared with 31% in both the potentially unlinked families and the reference groups (P=.03 for the tatter comparison). In the other clinical parameters, we found no significant differences between the groups, A modest excess of breast cancer and colon cancer was found in potentially linked families in comparison with potentially unlinked families, but this difference was not statistically significant. Conclusions.-Families that provide evidence for segregation of an altered HPC1 gene are characterized by multiple cases of prostate cancer that, in most respects, are indistinguishable from nonhereditary cases, However, 3 characteristics were observed: younger age at diagnosis, higher-grade tumors, and more advanced-stage disease, Our study shows that a significant fraction of hereditary prostate cancers are diagnosed in advanced stages, emphasizing the clinical importance of early detection in men potentially carrying prostate cancer susceptibility genes, These findings support the current recommendations to screen men with a positive family history of prostate cancer beginning at age 40 years. C1 JOHNS HOPKINS UNIV HOSP,JAMES BUCHANAN BRADY UROL INST,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. NATL HUMAN GENOME RES INST,NIH,BETHESDA,MD. UMEA UNIV,DEPT ONCOL,UMEA,SWEDEN. RI Smith, Jeff/C-3484-2012 FU NCI NIH HHS [CA58236] NR 21 TC 123 Z9 123 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 OCT 15 PY 1997 VL 278 IS 15 BP 1251 EP 1255 DI 10.1001/jama.278.15.1251 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA XZ709 UT WOS:A1997XZ70900030 PM 9333266 ER PT J AU Barcellos, LF Thomson, G Carrington, M Schafer, J Begovich, AB Lin, P Xu, XH Min, BQ Marti, D Klitz, W AF Barcellos, LF Thomson, G Carrington, M Schafer, J Begovich, AB Lin, P Xu, XH Min, BQ Marti, D Klitz, W TI Chromosome 19 single-locus and multilocus haplotype associations with multiple sclerosis - Evidence of a new susceptibility locus in Caucasian and Chinese patients SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID BASIC-PROTEIN GENE; MYELIN OLIGODENDROCYTE GLYCOPROTEIN; APOLIPOPROTEIN-E; LINKAGE DISEQUILIBRIUM; ALZHEIMERS-DISEASE; DIAGNOSTIC-CRITERIA; SHANGHAI CHINESE; HLA; POLYMORPHISM; COMPLEX AB Context.-Susceptibility to multiple sclerosis (MS) involves a genetically complex autoimmune component. However, except for genes in the HLA system, specific susceptibility loci are unknown or unconfirmed. Objective.-To investigate several loci spanning 3 candidate regions for a role in multiple sclerosis (MS) susceptibility in 2 ethnic groups using both single-locus and haplotype analyses. The 3 regions include HLA on chromosome 6p21.3, APOE on chromosome 19q13.2, and MBP (myelin basic protein) on chromosome 18q23. Design.-Case-control association testing. Subjects.-A total of 120 Caucasian patients with MS and 107 unrelated control individuals from California, and 32 patients and 32 unrelated control individuals from Beijing, China. All patients with MS were diagnosed as having clinically definite disease according to published criteria. Main Outcome Measures.-chi(2) Testing of loci and individual alleles and haplotypes. Haplotype frequencies were estimated with standard maximum likelihood methods. Results.-The HLA effect is due to the class II DR2 haplotype, DRB1*1501-DQA1*0102-DRB1*0602; contributions to MS susceptibility from additional DRB1-DQB1 alleles or other HLA region loci were not observed. Variation within the MBP locus on chromosome 18q23 showed no effect in MS. The distribution of haplotypes from 5 loci within the chromosome 19q13.2 region, including D19S178, D19S574, APOE, APOC2, and D19S219, differed between patient and control samples. D19S574 showed a significant effect (P=.015) in Caucasian patients with MS due to the increased frequency of a single allele (P=.002). The APOE variation, prominent in other neurological diseases, showed no influence on MS susceptibility, despite its location within the chromosome 19q13.2 region. interaction effects between DR2 and chromosome 19q13.2 or MBP in MS susceptibility were not apparent. Conclusions.-The significant chromosome 19q13.2 single-locus and multilocus haplotype associations with MS in Caucasian and Chinese patient samples indicate an effect from a nearby disease susceptibility locus. These initial observations are an encouraging step toward the description of non-HLA genetic susceptibility to MS. C1 UNIV CALIF BERKELEY,DEPT INTEGRAT BIOL,BERKELEY,CA 94720. ROCHE MOL SYST INC,DEPT HUMAN GENET,ALAMEDA,CA. CHILDRENS HOSP,OAKLAND RES INST,OAKLAND,CA 94609. NCI,INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. UNIV CALIF DAVIS,DEPT NEUROL,DAVIS,CA. BEIJING UNION MED COLL HOSP,DEPT NEUROL,BEIJING 100730,PEOPLES R CHINA. FU NIAID NIH HHS [AI29042]; NIGMS NIH HHS [GM35326] NR 57 TC 66 Z9 67 U1 0 U2 2 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 OCT 15 PY 1997 VL 278 IS 15 BP 1256 EP 1261 DI 10.1001/jama.278.15.1256 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA XZ709 UT WOS:A1997XZ70900031 PM 9333267 ER PT J AU Wong, FL Boice, JD Abramson, DH Tarone, RE Kleinerman, RA Stovall, M Goldman, MB Seddon, JM Tarbell, N Fraumeni, JF Li, FP AF Wong, FL Boice, JD Abramson, DH Tarone, RE Kleinerman, RA Stovall, M Goldman, MB Seddon, JM Tarbell, N Fraumeni, JF Li, FP TI Cancer incidence after retinoblastoma - Radiation dose and sarcoma risk SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SOFT-TISSUE SARCOMAS; BILATERAL RETINOBLASTOMA; HEREDITARY RETINOBLASTOMA; TRILATERAL RETINOBLASTOMA; SURVIVORS; TUMORS; RADIOTHERAPY; NEOPLASMS; CARCINOMAS; MORTALITY AB Context.-There is a substantial risk of a second cancer for persons with hereditary retinoblastoma, which is enhanced by radiotherapy. Objective.-To examine long-term risk of new primary cancers in survivors of childhood retinoblastoma and quantify the role of radiotherapy in sarcoma development. Design.-Cohort incidence study of patients with retinoblastoma followed for a median of 20 years, and nested case-control study of a radiation dose-response relationship for bone and soft tissue sarcomas. Setting/Participants.-A total of 1604 patients with retinoblastoma who survived at least 1 year after diagnosis, identified from hospital records in Massachusetts and New York during 1914 to 1984. Results.-Incidence of subsequent cancers was statistically significantly elevated only in the 961 patients with hereditary retinoblastoma, in whom 190 cancers were diagnosed, vs 6.3 expected in the general population (relative risk [RR], 30 [95% confidence interval, 26-47]), Cumulative incidence (+/-SE) of a second cancer at 50 years after diagnosis was 51.0% (+/-6.2%) for hereditary retinoblastoma, and 5.0% (+/-3.0%) for nonhereditary retinoblastoma. All 114 sarcomas of diverse histologic types occurred in patients with hereditary retinoblastoma. For soft tissue sarcomas, the RRs showed a stepwise increase at all dose categories, and were statistically significant at 10 to 29.9 Gy and 30 to 59.9 Gy. A radiation risk for all sarcomas combined was evident at doses above 5 Gy, rising to 10.7-fold at doses of 60 Gy or greater (P<.05). Conclusions.-Genetic predisposition has a substantial impact on risk of subsequent cancers in retinoblastoma patients, which is further increased by radiation treatment. A radiation dose-response relationship is demonstrated for all sarcomas and, for the first time in humans, for soft tissue sarcomas. Retinoblastoma patients should be examined for new cancers and followed into later life to determine whether their extraordinary cancer risk extends to common cancers of adulthood. C1 NCI,DIV CANC EPIDEMIOL & GENET,NIH,ROCKVILLE,MD 20892. UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX. NEW YORK HOSP,CORNELL MED CTR,NEW YORK,NY 10021. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA 02115. RI Wong, Fuhin/M-8360-2013; OI Kleinerman, Ruth/0000-0001-7415-2478 FU NCI NIH HHS [N01-CP-85604, N02-CP-33013] NR 38 TC 369 Z9 377 U1 2 U2 6 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 OCT 15 PY 1997 VL 278 IS 15 BP 1262 EP 1267 DI 10.1001/jama.278.15.1262 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA XZ709 UT WOS:A1997XZ70900032 PM 9333268 ER PT J AU Collins, FS AF Collins, FS TI Preparing health professionals for the genetic revolution SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID THERAPY; CANCER; STEPS RP Collins, FS (reprint author), NATL HUMAN GENOME RES INST,NIH,31 CTR DR,MSC 2152,BLDG 31,ROOM 4B09,BETHESDA,MD 20892, USA. NR 18 TC 64 Z9 64 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 OCT 15 PY 1997 VL 278 IS 15 BP 1285 EP 1286 DI 10.1001/jama.278.15.1285 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XZ709 UT WOS:A1997XZ70900038 PM 9333274 ER PT J AU Wosikowski, K Schuurhuis, D Johnson, K Paull, KD Myers, TG Weinstein, JN Bates, SE AF Wosikowski, K Schuurhuis, D Johnson, K Paull, KD Myers, TG Weinstein, JN Bates, SE TI Identification of epidermal growth factor receptor and c-erbB2 pathway inhibitors by correlation with gene expression patterns SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-Association-for-Cancer-Research CY APR 20-24, 1996 CL WASHINGTON, D.C. SP Amer Assoc Canc Res ID HUMAN-BREAST-CANCER; TYROSINE KINASE-ACTIVITY; ANTICANCER DRUG SCREEN; TUMOR-CELL-LINES; PSEUDOMONAS EXOTOXIN; SELECTIVE-INHIBITION; FACTOR-ALPHA; RESISTANCE; ONCOGENE; AMPLIFICATION AB Background: Growth factor receptor-signaling pathways are potentially important targets for anticancer therapy, The interaction of anticancer agents with specific molecular targets can be identified by correlating target expression patterns with cytotoxicity patterns, We sought to identify new agents that target and inhibit the activity of the epidermal growth factor (EGF) receptor and of c-erbB2 (also called HER2 or neu), by correlating EGF receptor, transforming growth factor (TGF)-alpha. (a ligand for EGF receptor), and c-erbB2 messenger RNA (mRNA) expression levels with the results of cytotoxicity assays of the 49 000 compounds in the National Cancer Institute (NCI) drug screen database, Methods: The levels of mRNAs were measured and used to generate a molecular target database for the 60 cell lines of the NCI anticancer drug screen, The computer analysis program, COMPARE, was used to search for cytotoxicity patterns in the NCI drug screen database that were highly correlated with EGF receptor, TGF-alpha, or c-erbB2 mRNA expression patterns, The putative EGF receptor-inhibiting compounds were tested for effects on basal tyrosine phosphorylation, in vitro EGF receptor tyrosine kinase activity, and EGF-dependent growth. Putative ErbB2-inhibiting compounds were tested for effects on antibody-induced ErbB2 tyrosine kinase activity, Results: EGF receptor mRNA and TGF-alpha mRNA levels were highest in cell lines derived from renal cancers, and c-erbB2 mRNA levels were highest in cells derived from breast, ovarian, and colon cancers. Twenty-five compounds with high correlation coefficients (for cytotoxicity and levels of the measured mRNAs) were tested as inhibitors of the EGF receptor or c-erbB2 signaling pathways; 14 compounds were identified as inhibitors of these pathways. The most potent compound, B4, inhibited autophosphorylation (which occurs following activation) of ErbB2 by 50% in whole cells at 7.7 mu M, Conclusions: Novel EGF receptor or c-erbB2 pathway inhibitors can be identified in the NCI drug screen by correlation of cytotoxicity patterns with EGF receptor or c-erbB2 mRNA expression levels. C1 NCI, DIV CLIN SCI, MED BRANCH, BETHESDA, MD 20892 USA. NCI, DIV CANC TREATMENT DIAGNOSIS & CTR, DEV THERAPEUT PROGRAM, INFORMAT TECHNOL BRANCH, BETHESDA, MD 20892 USA. NCI, LAB BASIC SCI, BETHESDA, MD 20892 USA. NR 49 TC 83 Z9 88 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD OCT 15 PY 1997 VL 89 IS 20 BP 1505 EP 1515 DI 10.1093/jnci/89.20.1505 PG 11 WC Oncology SC Oncology GA YA517 UT WOS:A1997YA51700011 PM 9337347 ER PT J AU Gorlach, A Lee, PL Roesler, J Hopkins, PJ Christensen, B Green, ED Chanock, SJ Curnutte, JT AF Gorlach, A Lee, PL Roesler, J Hopkins, PJ Christensen, B Green, ED Chanock, SJ Curnutte, JT TI A p47-phox pseudogene carries the most common mutation causing p47-phox-deficient chronic granulomatous disease SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE human chromosome 7; neutrophils; gene conversion; NADPH oxidase; respiratory burst ID RESPIRATORY BURST OXIDASE; PHAGOCYTE NADPH OXIDASE; STEROID 21-HYDROXYLASE GENES; AUTOSOMAL RECESSIVE FORMS; NEUTROPHIL CYTOCHROME-B; CYTOSOLIC COMPONENT; CHROMOSOMAL LOCATION; BINDING-SITE; LIGHT CHAIN; EXPRESSION AB The predominant genetic defect causing p47-phox-deficient chronic granulomatous disease (A47 degrees CGD) is a GT deletion (Delta GT) at the beginning of exon 2. No explanation exists to account for the high incidence of this single mutation causing a rare disease in an unrelated, racially diverse population, In each of 34 consecutive unrelated normal individuals, both the normal and mutant Delta GT sequences were present in genomic DNA, suggesting that a p47-phox related sequence carrying Delta GT exists in the normal population, Screening of genomic bacteriophage and YAC libraries identified 13 p47-phox bacteriophage and 19 YAC clones. The GT deletion was found in 11 bacteriophage and 15 YAC clones, Only 5 exonic and 33 intronic differences distinguished all Delta GT clones from all wild-type clones. The most striking differences were a 30-bp deletion in intron 1 and a 20-bp duplication in intron 2. These results provide good evidence for the existence of at least one highly homologous p47-phox pseudogene containing the Delta GT mutation, The p47-phox gene and pseudogene(s) colocalize to chromosome 7q11.23. This close linkage, together with the presence within each gene of multiple recombination hot spots, suggests that the predominance of the Delta GT mutation in A47 degrees CGD is caused by recombination events between the wildtype gene and the pseudogene(s). C1 GENENTECH INC, DEPT IMMUNOL, S SAN FRANCISCO, CA 94080 USA. Scripps Res Inst, DEPT MOL & EXPT MED, LA JOLLA, CA 92037 USA. SEQUANA THERAPEUT INC, LA JOLLA, CA 92037 USA. NCI, PEDIAT BRANCH, BETHESDA, MD 20892 USA. NIH, NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. RI Gorlach, Agnes/B-3494-2013 FU NCRR NIH HHS [RR00833]; NIAID NIH HHS [R01 AI24838] NR 58 TC 80 Z9 82 U1 0 U2 1 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 OCT 15 PY 1997 VL 100 IS 8 BP 1907 EP 1918 DI 10.1172/JCI119721 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA YC366 UT WOS:A1997YC36600002 PM 9329953 ER PT J AU Blauvelt, A Asada, H Saville, MW KlausKovtun, V Altman, DJ Yarchoan, R Katz, SI AF Blauvelt, A Asada, H Saville, MW KlausKovtun, V Altman, DJ Yarchoan, R Katz, SI TI Productive infection of dendritic cells by HIV-1 and their ability to capture virus are mediated through separate pathways SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE dendritic cells; HIV/AIDS; CCR-5; CXCR-4; immunopathogenesis ID EPIDERMAL LANGERHANS CELLS; CD4+ T-CELLS; IMMUNODEFICIENCY-VIRUS; IN-VITRO; HUMAN KERATINOCYTES; HUMAN BLOOD; TNF-ALPHA; GM-CSF; REPLICATION; TYPE-1 AB There is substantial evidence that dendritic cells (DC) residing within epithelial surfaces (e.g., Langerhans cells) are the initial cells infected with HIV after mucosal exposure to vi rus. To study DC-HIV interactions in detail, we propagated Langerhans cell-like DC from cord blood CD34(+) cells and from adult blood plastic-adherent PBMC in the presence of cytokines (GM-CSF, IL-4, and/or TNF-alpha). DC pulsed overnight with HIVBaL or HIVIIIB were infected productively with both viral subtypes (as assessed by PCR, supernatant p24 protein levels, electron microscopy, and antibody staining), Productive infection could be blocked by anti-CD4 mAbs, RANTES (regulated upon activation, normal T cell expressed and secreted) (for HIVBaL), stromal cell-derived factor-1 (for HIVIIIB), Or azidothymidine added during the HIV pulse, as well as by blocking DC proliferation, However, pulsing DC with HIV under these blocking conditions had no effect on the ability of DC to capture virus and transmit infection to cocultured antigen-stimulated CD4(+) T cells, Thus, we show by several criteria that (a) productive infection of DC and (b) the ability of DC to capture virus are mediated through separate pathways, We suggest that strategies designed to block mucosal transmission of HIV should consider interfering with both virus infection and virus capture by DC. C1 NCI,HIV & AIDS MALIGNANCY BRANCH,BETHESDA,MD 20892. RP Blauvelt, A (reprint author), NCI,DERMATOL BRANCH,BLDG 10,ROOM 12N238,10 CTR DR,MSC 1908,BETHESDA,MD 20892, USA. NR 49 TC 152 Z9 155 U1 2 U2 9 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 OCT 15 PY 1997 VL 100 IS 8 BP 2043 EP 2053 DI 10.1172/JCI119737 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA YC366 UT WOS:A1997YC36600018 PM 9329969 ER PT J AU Shibutani, T Johnson, TM Yu, ZX Ferrans, VJ Moss, J Epstein, SE AF Shibutani, T Johnson, TM Yu, ZX Ferrans, VJ Moss, J Epstein, SE TI Pertussis toxin-sensitive G proteins as mediators of the signal transduction pathways activated by cytomegalovirus infection of smooth muscle cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE cytosolic phospholipase A(2); reactive oxygen species; mitogen-activated protein kinase; nuclear factor kappa B; arachidonic acid ID CYTOSOLIC PHOSPHOLIPASE A(2); GROWTH-FACTOR; MAP KINASE; ARACHIDONIC-ACID; EXPRESSION; BINDING; PHOSPHORYLATION; IDENTIFICATION; RESTENOSIS; INHIBITION AB We demonstrated recently that the arachidonic acid (AA) cascade is involved in cytomegalovirus (CMV)-induced generation of reactive oxygen species (ROS) and the activation of nuclear factor (NF)-kappa B in human smooth muscle cells (SMCs). Since AA release from neutrophils is mediated by pertussis toxin (PTx)-sensitive guanine nucleotide-binding (G) proteins, we hypothesized by analogy that CMV stimulates ROS generation in SMCs and ultimately activates NF-kappa B via a PTx-sensitive G protein-coupled pathway. Our first test of this hypothesis demonstrated that PTx blocked AA release induced by CMV infection of SMCs, as well as blocked the terminal products of this reaction, ROS generation and NF-kappa B activation. More proximal components of the pathway were then examined. CMV infection increased phosphorylation and activity of cytosolic phospholipase A(2) (cPLA(2)), an enzyme causing AA release; these effects were inhibited by PTx. CMV infection activated mitogen-activated protein (MAP) kinase, a key enzyme for cPLA(2) phosphorylation, an effect also inhibited by PTx. Finally, inhibition of MAP kinase kinase (MAPKK), which phosphorylates and thereby activates MAP kinase, inhibited CMV-induced ROS generation. These data demonstrate that a PTx-sensitive G protein-dependent signaling pathway mediates cellular effects of CMV infection of SMCs. The downstream events include phosphorylation and activation of MAP kinase by MAPKK and subsequent phosphorylation and activation of cPLA(2) (with its translocation to cell membranes), followed by stimulation of the AA cascade, which generates intracellular ROS and thereby activates NF-kappa B. C1 NHLBI,CARDIOL BRANCH,NIH,BETHESDA,MD 20892. NHLBI,PATHOL SECT,NIH,BETHESDA,MD 20892. NHLBI,PULM & CRIT CARE MED BRANCH,NIH,BETHESDA,MD 20892. NR 35 TC 49 Z9 53 U1 0 U2 1 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 OCT 15 PY 1997 VL 100 IS 8 BP 2054 EP 2061 DI 10.1172/JCI119738 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA YC366 UT WOS:A1997YC36600019 PM 9329970 ER PT J AU Huang, H HuLi, J Chen, HJ BenSasson, SZ Paul, WE AF Huang, H HuLi, J Chen, HJ BenSasson, SZ Paul, WE TI IL-4 and IL-13 production in differentiated T helper type 2 cells is not IL-4 dependent SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RESTING B-CELLS; RECEPTOR EXPRESSION; RESPONSIVE ELEMENT; INTERLEUKIN-4 GENE; EPSILON-PROMOTER; CHROMOSOMAL GENE; GROWTH-FACTOR; FC-EPSILON; TRANSCRIPTION; INDUCTION AB CD4(+) T cell differentiation into cells capable of producing IL-4 and IL-13 (Th2 cells) requires the presence of IL-4 and is STAT-6 dependent. Here we show that IL-4 is not required for IL-4 or IL-13 production by Th2 cells. Anti-IL-4 or anti-IL-4R Ab did not diminish IL-4 production by Th2 cells in response to TCR-mediated stimulation, nor did IL-4 enhance IL-4 production in response to stimulation of Th2 cells with limiting amounts of Ag. Th2 cells prepared from IL-4 knockout mice were capable of producing IL-13 mRNA in response to stimulation with immobilized anti-CD3. IL-4 did not increase IL-13 mRNA expression. Despite the failure of IL-4 to effect IL-4 production by primed Th2 cells, a STAT-6 binding element was demonstrated in the IL-4 promoter. The authenticity of this element was demonstrated by oligonucleotide competition, by supershifting with anti-STAT-6 Ab, and by IL-4-inducible effects on transcription of a reporter gene under the control of a multimerized element fused to an IL-4 minimal promoter. Nonetheless, an IL-4 promoter construct lacking the STAT-6 binding element was as effective as a construct containing this element in anti-CD3-induced reporter transcription. Thus, this element, if biologically active, must function at a step in T cell responsiveness distinct from the acute production of IL-4 by Th2 cells in response to Ag or anti-CD3. C1 NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,HADASSAH MED CTR,LAUTENBERG CTR GEN & TUMOR IMMUNOL,JERUSALEM,ISRAEL. NR 35 TC 73 Z9 73 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 OCT 15 PY 1997 VL 159 IS 8 BP 3731 EP 3738 PG 8 WC Immunology SC Immunology GA XZ994 UT WOS:A1997XZ99400008 PM 9378959 ER PT J AU Mongini, PKA Vilensky, MA Highet, PF Inman, JK AF Mongini, PKA Vilensky, MA Highet, PF Inman, JK TI The affinity threshold for human B cell activation via the antigen receptor complex is reduced upon co-ligation of the antigen receptor with CD21 (CR2) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-DEPENDENT ANTIGEN; HUMAN LYMPHOCYTES-B; EPSTEIN-BARR VIRUS; COBRA VENOM FACTOR; IMMUNE-RESPONSE; MEMBRANE IGM; ANTIBODY-RESPONSE; CYCLE PROGRESSION; ACQUIRED-IMMUNITY; BINDING AB The present studies have examined whether the potential of an Ag to co-ligate the complement (C3d)-binding CD21 receptor complex with the membrane IgM (mIgM) receptor complex can reduce the mIgM:Ag affinity threshold for triggering human B cell S phase entry. A series of Ab:dextran conjugates consisting of affinity-diverse anti-IgM mAb, with and without anti-CD21 mAb, were synthesized as polyclonally reactive, moderately multivalent ligands that mimic C3d-bearing and non-C3d-bearing Ag. Co-ligation of mIgM and CD21 significantly diminished both the ligand concentration threshold and the IgM:ligand affinity threshold for eliciting S phase entry in the presence of IL-4. Furthermore, such co-engagement ablated the triggering bonus associated with high mIgM:ligand affinity, suggesting that B cells with a high affinity for Ag are not preferentially activated over B cells of intermediate affinity upon encountering a multivalent Ag with bound C3d. The enhancing effects of mIgM:CD21 co-ligation were restricted to law concentrations of ligand; at high concentrations, a decrease in B cell DNA synthesis was often observed. The findings suggest that the ability of a moderately multivalent Ag substrate to engage B cells through both mIgM and CD21 is critical for B cell activation at limiting Ag concentrations, and furthermore, that mIgM:CD21 co-engagement may be particularly important in eliciting an immune response to such Ags in unprimed individuals in whom the majority of specific B cells are of low affinity. C1 NYU,SCH MED,KAPLAN COMPREHENS CANC CTR,DEPT PATHOL,NEW YORK,NY 10016. NIH,IMMUNOL LAB,BETHESDA,MD 20892. RP Mongini, PKA (reprint author), HOSP JOINT DIS & MED CTR,DEPT RHEUMATOL,301 E 17TH ST,NEW YORK,NY 10003, USA. FU NIGMS NIH HHS [GM-35174] NR 59 TC 64 Z9 68 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 OCT 15 PY 1997 VL 159 IS 8 BP 3782 EP 3791 PG 10 WC Immunology SC Immunology GA XZ994 UT WOS:A1997XZ99400014 PM 9378965 ER PT J AU Hornung, F Zheng, LX Lenardo, MJ AF Hornung, F Zheng, LX Lenardo, MJ TI Maintenance of clonotype specificity in CD95/Apo-1/Fas-mediated apoptosis of mature T lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; FAS GENE-MUTATIONS; LYMPHOPROLIFERATIVE SYNDROME; SIGNALING COMPLEX; DEATH DOMAIN; CELL-DEATH; RECEPTOR; TNF; ACTIVATION; MICE AB Ag-induced mature T cell apoptosis is the result of death-inducing cytokines, including the ligand for CD95 (Apo-1/Fas). This raises the possibility that expression of this death molecule could affect bystander T cells that were not directly antigenically stimulated but that express the CD95 receptor. We show here that bystander T cells, even if they express the CD95 receptor, are not killed when exposed to T cells undergoing Ag-induced apoptosis. Rather, cell death is restricted to T cells that bear the receptor clonotype that is specifically engaged by TCR ligands. At least one mechanism of clonotype restriction is a significant enhancement of CD95-induced apoptosis by TCR ligation. Our results demonstrate that, in addition to the well-known ability of TCR to stimulate apoptosis by inducing CD95 ligand expression, TCR signals at the time of CD95 engagement can effectively increase apoptosis. Therefore, we pot forward the hypothesis that strict clonotype specificity is preserved when death cytokines such as CD95 ligand induce autoregulatory mature T cell apoptosis, at least in part through a sensitization signal provided by the TCR stimulation. C1 NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. UNIV FREIBURG,FREIBURG,GERMANY. NR 36 TC 45 Z9 45 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 OCT 15 PY 1997 VL 159 IS 8 BP 3816 EP 3822 PG 7 WC Immunology SC Immunology GA XZ994 UT WOS:A1997XZ99400018 PM 9378969 ER PT J AU Czerniecki, BJ Carter, C Rivoltini, L Koski, GK Kim, HI Weng, DE Roros, JG Hijazi, YM Xu, SW Rosenberg, SA Cohen, PA AF Czerniecki, BJ Carter, C Rivoltini, L Koski, GK Kim, HI Weng, DE Roros, JG Hijazi, YM Xu, SW Rosenberg, SA Cohen, PA TI Calcium ionophore-treated peripheral blood monocytes and dendritic cells rapidly display characteristics of activated dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; EPIDERMAL LANGERHANS CELLS; ANTIGEN-PRESENTING CELLS; T-CELLS; ACCESSORY CELLS; COSTIMULATORY MOLECULE; NAIVE PRECURSORS; GM-CSF; MATURE; DIFFERENTIATION AB Human peripheral blood contains a small subpopulation of immature dendritic cells (iDC) distinguished from circulating monocytes by their low expression of CD14. We utilized leukapheresis and countercurrent centrifugal elutriation to obtain myeloid origin mononuclear cell (MOMC) fractions of monocytes and iDC for study. These subpopulations were ultrastructurally and immunophenotypically similar before culture. After a 20- to 96-h culture either alone, with recombinant human granulocyte-monocyte CSF, or with endotoxin, greater up-regulation of costimulatory molecule expression was observed among iDC than among monocytes, and only iDC expressed the activation molecule CD83. Treatment with rhIL-4 caused many MOMC to develop morphologic properties of dendritic cells within 96 h, but costimulatory molecule up-regulation and CD14 down-regulation were heterogeneous, and CD83 expression was infrequent. In contrast, calcium ionophore (CI) treatment induced rapid and consistent effects in MOMC from both healthy volunteers and cancer patients, including down-regulated CD14 expression, acquisition of dendritic cell morphologic properties, up-regulated MHC and costimulatory molecule expression, and de novo CD83 expression. Many such effects occurred within 20 h of treatment. CI treatment activated purified CD14(+) monocytes and also enhanced the spontaneous activation of purified CD14(-/dim) iDC in culture. Unfractionated MOMC, purified monocytes, and purified iDC displayed equivalently enhanced T cell-sensitizing efficiency following CI treatment. CD4(+) T cell sensitization to keyhole limpet hemocyanin and CD8(+) T cell sensitization to MART-1 melanoma-associated peptide were achieved in a single culture stimulation. Therefore, circulating monocytes and iDC can be induced by CI to manifest properties of activated DC, providing large numbers of efficient, nontransformed autologous APC for T cell sensitization strategies. C1 NCI,DEPT TRANSFUS MED,WARREN GRANT MAGNUSON CLIN CTR,NIH,BETHESDA,MD 20892. NCI,SURG BRANCH,NIH,BETHESDA,MD 20892. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NCI,MED ONCOL BRANCH,NIH,BETHESDA,MD 20892. RP Czerniecki, BJ (reprint author), UNIV PENN,MED CTR,DEPT SURG,4 SILVERSTEIN,3400 SPRUCE ST,PHILADELPHIA,PA 19104, USA. OI Rivoltini, Licia/0000-0002-2409-6225 NR 59 TC 138 Z9 147 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 OCT 15 PY 1997 VL 159 IS 8 BP 3823 EP 3837 PG 15 WC Immunology SC Immunology GA XZ994 UT WOS:A1997XZ99400019 PM 9378970 ER PT J AU Hartmann, K WagelieSteffen, AL vonStebut, E Metcalfe, DD AF Hartmann, K WagelieSteffen, AL vonStebut, E Metcalfe, DD TI Fas (CD95,APO-1) antigen expression and function in murine mast cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID C-KIT LIGAND; ANTIBODY-MEDIATED APOPTOSIS; HUMAN B-LYMPHOCYTES; PROGENITOR CELLS; GROWTH-FACTOR; BONE-MARROW; DIFFERENTIAL EXPRESSION; DNA FRAGMENTATION; T-LYMPHOCYTES; TNF-ALPHA AB As an extension of the observation that mast cells undergo apoptosis following growth factor deprivation, we hypothesized that mast cells might also undergo apoptosis in response to activation through Fas Ag (CD95, APO-1), thus providing arm additional pathway that could contribute to the regulation of mast cell numbers, Surface expression of Fas Ag was studied by flow cytometry, and apoptotic changes following treatment with anti-fas mAb were analyzed using flow cytometric analysis of PI uptake and TUNEL staining, DNA electrophoresis, and electron microscopy. Murine bone marrow-cultured mast cells (BMCMC) and peritoneal mast cells, as well as two mast cell lines (C57 and MCP-5), constitutively expressed Fas Ag. Aggregation of Fas ag with anti-Fas mAb resulted in the characteristic changes of apoptosis in C57 mast cells, BMCMC were resistant to anti-fas mAk, alone, but after the addition of actinomycin D also exhibited apoptosis in response to anti-Fas treatment. In addition, actinomycin D alone induced apoptosis. Stent cell factor, TGF-beta, and Fc epsilon RI aggregation enhanced Fas expression, However, Fas-mediated apoptosis was not augmented by Fc epsilon RI aggregation, and stem cell factor and TGF-beta partially protected BMCMC against Fas-mediated cytotoxicity, Finally, C57 mast cells were highly susceptible tea killing by a Fas ligand-bearing CTL hybridoma, white BMCMC were relatively resistant, consistent with the results using anti-Fas mAb. Thus, induction of mast cell apoptosis by activation of the Fas pathway provides an additional mechanism by which mast cell numbers may be regulated in biologic systems. C1 NIAID,LAB ALLERG DIS,NIH,BETHESDA,MD 20892. HUMBOLDT UNIV BERLIN,BEREICH MED CHARITE,DEPT DERMATOL,BERLIN,GERMANY. RI Hartmann, Karin/N-4865-2015 OI Hartmann, Karin/0000-0002-4595-8226 NR 59 TC 41 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 OCT 15 PY 1997 VL 159 IS 8 BP 4006 EP 4014 PG 9 WC Immunology SC Immunology GA XZ994 UT WOS:A1997XZ99400039 PM 9378990 ER PT J AU Lafrenie, RM Wahl, LM Epstein, JS Yamada, KM Dhawan, S AF Lafrenie, RM Wahl, LM Epstein, JS Yamada, KM Dhawan, S TI Activation of monocytes by HIV-Tat treatment is mediated by cytokine expression SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; PERIPHERAL-BLOOD MONOCYTES; IMMUNE-DEFICIENCY-SYNDROME; HUMAN SYNOVIAL-CELLS; GENE-EXPRESSION; TNF-ALPHA; TRANSCRIPTIONAL ACTIVATION; STIMULATES COLLAGENASE; DERMAL FIBROBLASTS AB Treatment of primary monocytes with soluble HIV-Tat protein is associated with increased monocyte metalloproteinase-9 (MMP-9) expression and enhanced beta(2) integrin expression that increases monocyte/endothelial adhesion. These alterations require greater than 12 h of HIV-Tat treatment, suggesting the involvement of intermediate factors. Thus, we have examined the role of cytokines in the HIV-Tat-induced alteration of monocyte function. Treatment of monocytes with HIV-Tat rapidly upregulated the production of IL-1 beta, IL-6, IL-8, and TNF-alpha, but not IL-3, granulocyte-macrophage CSF, basic fibroblast growth factor, or macrophage-inflammatory protein-1 alpha, and was associated with up-regulation of the corresponding cytokine mRNA. Inclusion of neutralizing anti-cytokine Abs to IL-1 beta or TNF-alpha during the HIV-Tat pretreatment period significantly inhibited the HIV-Tat-induced increase in MMP-9 production, monocyte/endothelial adhesion, and monocyte-dependent endothelial damage. In contrast, neutralizing Abs against IL-6 and IL-8 had no effect. The effects of HIV-Tat treatment, namely MMP-9 production, enhanced monocyte/endothelial cell adhesion, and monocyte-dependent endothelial damage, were mimicked by treating the monocytes with IL-1 beta or TNF-alpha, but not with IL-6 or IL-8. Therefore, the mechanism by which HIV-Tat activates monocyte function is dependent on HIV-Tat-induced production of cytokines (IL-1 beta and TNF-alpha). C1 US FDA,LAB IMMUNOCHEM,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,ROCKVILLE,MD 20852. NIDR,CRANIOFACIAL DEV BIOL & REGENERAT BRANCH,BETHESDA,MD 20892. NIDR,MATRIX METALLOPROT UNIT,BETHESDA,MD 20892. OI Yamada, Kenneth/0000-0003-1512-6805 NR 55 TC 92 Z9 95 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 OCT 15 PY 1997 VL 159 IS 8 BP 4077 EP 4083 PG 7 WC Immunology SC Immunology GA XZ994 UT WOS:A1997XZ99400047 PM 9378998 ER PT J AU Kim, JG Armstrong, RC vonAgoston, D Robinsky, A Wiese, C Nagle, J Hudson, LD AF Kim, JG Armstrong, RC vonAgoston, D Robinsky, A Wiese, C Nagle, J Hudson, LD TI Myelin transcription factor 1 (Myt1) of the oligodendrocyte lineage, along with a closely related CCHC zinc finger, is expressed in developing neurons in the mammalian central nervous system SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE zinc finger; transcription factor; differentiating neurons; oligodendrocyte progenitors; myelin ID BETA-TUBULIN; GENE; PROTEIN; ELEMENTS; BRAIN AB The establishment and operation of the nervous system requires genetic regulation by a network of DNA-binding proteins, among which is the zinc finger superfamily of transcription factors, We have cloned and characterized a member of the unusual Cys-Cys-His-Cys (also referred to as Cys(2)HisCys, CCHC, or C2HC) class of zinc finger proteins in the developing nervous system, The novel gene, Myt1-like (Myt1l), is highly homologous to the original representative of this class, Myelin transcription factor 1 (Myt1) (Kim and Hudson, 1992), The MYT1 gene maps to human chromosome 20, while MYT1L maps to a region of human chromosome 2, Both zinc finger proteins are found in neurons at early stages of differentiation, with germinal zone cells displaying intense staining for MyT1. Unlike Myt1, Myt1l has not been detected in the glial lineage, Neurons that express Myt1l also express TuJ1, which marks neurons around the period of terminal mitosis, The Myt1l protein resides in distinct domains within the neuronal nucleus, analogous to the discrete pattern previously noted for Myt1 (Armstrong et al.: 14:303-321, 1995), The developmental expression and localization of these two multifingered CCHC proteins suggests that each may play a role in the development of neurons and oligodendroglia in the mammalian central nervous system. (C) 1997 Wiley-Liss, Inc.dagger. C1 NINCDS,LAB DEV NEUROGENET,NIH,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT ANAT & CELL BIOL,BETHESDA,MD 20814. NICHHD,DEV NEUROBIOL LAB,NIH,BETHESDA,MD 20892. HOFFMANN LA ROCHE AG,PRECLIN RES,BASEL,SWITZERLAND. NINCDS,SEQUENCING FACIL,NIH,BETHESDA,MD 20892. NR 28 TC 73 Z9 76 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD OCT 15 PY 1997 VL 50 IS 2 BP 272 EP 290 DI 10.1002/(SICI)1097-4547(19971015)50:2<272::AID-JNR16>3.0.CO;2-A PG 19 WC Neurosciences SC Neurosciences & Neurology GA YD831 UT WOS:A1997YD83100015 PM 9373037 ER PT J AU Bilski, P Holt, RN Chignell, CF AF Bilski, P Holt, RN Chignell, CF TI Premicellar aggregates of Rose Bengal with cationic and zwitterionic surfactants SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY LA English DT Article DE Rose Bengal; premicellar aggregates; dye-rich-micelles; surfactants; cetylpyridinium chloride; zwitterionic surfactants; salts; free exciton; ion pairs ID CRITICAL MICELLE CONCENTRATION; AQUEOUS-SOLUTION; ABSORPTION-SPECTRA; ENERGY-TRANSFER; XANTHENE DYES; FLUORESCENCE; SYSTEMS; EXCITON; EOSIN; DYNAMICS AB Transition from non-micellar to micellar Rose Bengal (RE) may involve little known species which are usually called dye-rich-micelles or premicellar aggregates (PAs). We have studied the PAs formed between RE and a series of surfactants with a zwitterionic alkylsulfobetaine functionality, SB-X, where X = 8, 10, 12, 14 or 16 carbon atoms in the alkyl chain. We have compared these aggregates to those formed between RE and the cationic surfactant cetylpyridinium chloride. In most of the PAs studied, the formation of aggregates broadened and red-shifted ( similar to 10 nm) Rose Bengal's absorption and fluorescence, and decreased the intensity compared to the absorption and fluorescence bands of free RE in water. Such properties are characteristic of J-aggregates in which the RE molecules are loosely organized in a 'head-to-tail' fashion. The formation of all PAs containing RE was increased by the addition of salts producing water-soluble aggregates. Addition of salts such as KCI, Na2SO4 or MgCl2 (0.2-1.5 M) to the PAs formed exclusively between RE and SB-12 induced the formation of novel J-aggregates in which the dye absorption band was very narrow, red-shifted by 37 nm, and almost three times more intense. The novel PAs are stable in solution and even co-existed with RE in SB-12 micelles at high salt concentrations. They were not formed by eosine or salts having large polarizable anions such as ClO4- or I-. They also were not formed with other surfactants, except when SB-IO was used instead of SB-12 in MgSO4 solution. The spectral properties of RE in novel J-PAs indicate a higher level of molecular organization, which may lead to free exciton transitions between the dye molecules as a result of strong dipole-dipole coupling. Our results also confirm that the formation of hydrophobic ion pairs between the RE dianion and the cationic center in surfactant molecules initiates premicellar aggregation (Bilski et al., J. Phys. Chem., 95 (1991) 5784). Some of the resultant salt-induced PAs must be highly structured, which strongly affects the spectral properties of Rose Bengal. (C) 1997 Elsevier Science S.A. RP Bilski, P (reprint author), NIEHS, MOL BIOPHYS LAB, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 57 TC 41 Z9 41 U1 0 U2 9 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1010-6030 J9 J PHOTOCH PHOTOBIO A JI J. Photochem. Photobiol. A-Chem. PD OCT 15 PY 1997 VL 110 IS 1 BP 67 EP 74 DI 10.1016/S1010-6030(97)00166-4 PG 8 WC Chemistry, Physical SC Chemistry GA YF957 UT WOS:A1997YF95700011 ER PT J AU Ottiger, M Tjandra, N Bax, A AF Ottiger, M Tjandra, N Bax, A TI Magnetic field dependent amide N-15 chemical shifts in a protein-DNA complex resulting from magnetic ordering in solution SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID RELAXATION INTERFERENCE; NMR-SPECTROSCOPY; POWDER PATTERNS; HUMAN UBIQUITIN; PEPTIDE-BOND; DIPOLAR; TENSORS; BACKBONE; SPECTRA; ANISOTROPY AB In solution, the degree of molecular alignment with the static magnetic field is proportional to the product of the anisotropy of the molecular magnetic susceptibility and the square of the magnetic field strength. As a result, the observed chemical shifts vary with the strength of the magnetic field and depend on the orientation of the chemical shift tensors relative to the molecule's magnetic susceptibility tensor. For protein backbone amide N-15 nuclei in the complex between the zinc-finger DNA-binding domain of GATA-1 and a 16-bp synthetic DNA fragment, the observed field dependence of the N-15 shifts correlates well with the dipolar couplings previously reported for this complex. This comparison indicates that, in the approximation of an axially symmetric N-15 shift tensor, the unique axis of the N-15 CSA tensor makes an angle of 13 +/- 5 degrees with the N-H bond vector, and has a magnitude of 168 +/- 20 ppm. Magnetic field dependent N-15 chemical shifts correlate well with the structure of the protein-DNA complex refined with H-1-N-15 and C-13(alpha)-H-1(alpha) dipolar coupling constraints, but poorly with the original structure of this complex, despite relatively small rms differences between the two ensembles of structures. Magnetic field dependent chemical shifts therefore are potentially quite useful as constraints in macromolecular structure determination. C1 NIDDKD,PHYS CHEM LAB,NIH,BETHESDA,MD 20892. NHLBI,BIOPHYS CHEM LAB,NIH,BETHESDA,MD 20892. NR 33 TC 73 Z9 73 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD OCT 15 PY 1997 VL 119 IS 41 BP 9825 EP 9830 DI 10.1021/ja971639e PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA YB372 UT WOS:A1997YB37200025 ER PT J AU Kaye, FJ AF Kaye, FJ TI Can p53 status resolve paradoxes between human and non-human retinoblastoma models? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID TRANSGENIC MICE; GENE-PRODUCT; ADENOVIRUS; MUTATION; PROTEIN; TUMORS; APOPTOSIS; BIND C1 NCI,MED BRANCH,DIV CLIN SCI,BETHESDA,MD 20892. RI kaye, frederic/E-2437-2011 NR 22 TC 4 Z9 4 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 OCT 15 PY 1997 VL 89 IS 20 BP 1476 EP 1477 DI 10.1093/jnci/89.20.1476 PG 2 WC Oncology SC Oncology GA YA517 UT WOS:A1997YA51700003 PM 9337339 ER PT J AU Ershler, WB Longo, DL AF Ershler, WB Longo, DL TI Aging and cancer: Issues of basic and clinical science SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID ACUTE MYELOID-LEUKEMIA; LYMPHOCYTE-INDUCED ANGIOGENESIS; SENESCENT HUMAN-FIBROBLASTS; COLONY-STIMULATING FACTOR; CYCLE-DEPENDENT GENES; TUMOR-GROWTH; DNA-REPAIR; CHEMOTHERAPEUTIC-AGENTS; ALZHEIMERS-DISEASE; IMMUNE FUNCTION AB The majority of patients with cancer in the United States are more than 70 years old. Despite the increased understanding of the molecular bases for both oncogenesis and aging, the overlap of cancer and aging at that level remains a wide-open research domain. Similarly, at the clinical level, there is also an increased awareness of the need for more information about the influence of host age on the development of tumors, on the growth and spread of the disease, and on treatment expectations. In this review, we have attempted to frame questions regarding cancer and aging from the perspective of biogerontology and geriatric medicine, An increased effort to address the issues of aging is of paramount importance at all levels of cancer investigation. C1 EASTERN VIRGINIA MED SCH,GLENNAN CTR GERIATR & GERONTOL,NORFOLK,VA 23501. RP Ershler, WB (reprint author), NIA,GERONTOL RES CTR,NIH,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 122 TC 84 Z9 86 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 OCT 15 PY 1997 VL 89 IS 20 BP 1489 EP 1497 DI 10.1093/jnci/89.20.1489 PG 9 WC Oncology SC Oncology GA YA517 UT WOS:A1997YA51700009 PM 9337345 ER PT J AU Smith, MA Chen, T Simon, R AF Smith, MA Chen, T Simon, R TI Age-specific incidence of acute lymphoblastic leukemia in US children: In utero initiation model SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SIMIAN VIRUS-40; JC VIRUS; CHILDHOOD LEUKEMIA; INFANT LEUKEMIA; T-ANTIGEN; IDENTIFICATION; TRANSFORMATION; INTERMEDIATE; ETIOLOGY; GENOMES C1 NCI,CANC THERAPY EVALUAT PROGRAM,DIV CANC TREATMENT DIAGNOSIS & CTR,BETHESDA,MD 20892. NR 19 TC 28 Z9 28 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 OCT 15 PY 1997 VL 89 IS 20 BP 1542 EP 1544 DI 10.1093/jnci/89.20.1542 PG 3 WC Oncology SC Oncology GA YA517 UT WOS:A1997YA51700016 PM 9337352 ER PT J AU Bishop, JF Joshi, G Mueller, GP Mouradian, MM AF Bishop, JF Joshi, G Mueller, GP Mouradian, MM TI Localization of putative calcium-responsive regions in the rat BDNF SO MOLECULAR BRAIN RESEARCH LA English DT Article DE brain-derived neurotrophic factor; neurotrophic; transcription regulation; calcium; C6 glioma cell ID NEUROTROPHIC FACTOR GENE; DOPAMINERGIC-NEURONS; MESSENGER-RNAS; MULTIPLE PROMOTERS; BRAIN INSULTS; EXPRESSION; DISEASE; IDENTIFICATION; INITIATION; ACTIVATION AB Brain-derived neurotrophic factor (BDNF) has potent trophic and protective actions on CNS dopaminergic neurons, ventral forebrain cholinergic neurons and spinal motor neurons. To evaluate the effects of calcium and other second messengers on BDNF gene transcription, C6 glioma cells were treated for 4 h with the calcium ionophore A23187, forskolin + isobutyl-methyl-xanthine (IBMX), or the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate. Semi-quantitative RT-PCR analysis revealed that A23187 treatment increased BDNF transcripts containing the protein coding exon by 4.4-6.4-fold. Alternate BDNF transcripts were elevated to varying degree after treatment with this ionophore and a subset of these transcripts was elevated following forskolin + IBMX treatment. When co-incubated with the RNA polymerase inhibitor, actinomycin D, A23187-induced increases were reduced or abolished, suggesting that calcium-mediated regulation Of BDNF mRNA expression occurs at transcriptional as well as post-transcriptional levels. Transient transfection experiments employing reporter constructs containing serial 5' deletions of alternate BDNF promoters suggested that A23187-induced elevations in BDNF exon Ib, Id and Ie containing transcripts are mediated by putative calcium-responsive regions flanking all three of these exons. (C) 1997 Elsevier Science B.V. C1 NINCDS,EXPT THERAPEUT BRANCH,NIH,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT PHYSIOL,BETHESDA,MD 20892. NR 41 TC 18 Z9 18 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 OCT 15 PY 1997 VL 50 IS 1-2 BP 154 EP 164 DI 10.1016/S0169-328X(97)00180-0 PG 11 WC Neurosciences SC Neurosciences & Neurology GA YF868 UT WOS:A1997YF86800020 ER PT J AU Pondarre, C Strumberg, D Fujimori, A TorresLeon, R Pommier, Y AF Pondarre, C Strumberg, D Fujimori, A TorresLeon, R Pommier, Y TI In vivo sequencing of camptothecin-induced topoisomerase I cleavage sites in human colon carcinoma cells SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RIBOSOMAL-RNA GENES; HEAT-SHOCK GENES; EUKARYOTIC TOPOISOMERASE; CALF THYMUS; DNA; TRANSCRIPTION; INHIBITOR; METHYLATION; INDUCTION; ABSENCE AB Camptothecin (CPT) is a specific topoisomerase I (top1) poison which traps top1 cleavable complexes; e.g. top1-linked DNA single-strand breaks with 5'-hydroxyl and 3'-top1 linked termini, CPT is also a potent anticancer agent and several of its derivatives have recently shown activity in the chemotherapy of solid tumors, Our aim was to apply the ligation-mediated polymerase chain reaction (LM-PCR) method to DNA extracted from CPT-treated cells in order to: (i) evaluate LM-PCR as a sensitive technique to detect in vivo OPT-induced cleavable complexes; (ii) investigate the frequency and distribution of CPT-induced DNA damage in vivo; and (iii) compare the distribution and intensity of cleavage sites in vivo and in vitro. This report describes a protocol allowing the sequencing of top1-mediated DNA strand breaks induced by CPT in the coding strand of the 18S rRNA gene of human colon carcinoma cells, CPT or its clinical derivatives, topotecan, CPT-11, SN-38, and O-aminocamptothecin differed in their potency and exhibited differences in their DNA cleavage pattern, which is consistent with our previous in vitro studies [Tanizawa et al. (1995) Biochemistry, 43, 7200-7206]. CPT-induced DNA cleavages induced in the presence of purified top1 were induced at the same sites in the human 18S rDNA. However; the relative intensity of the cleavages were different in vivo and in vitro, Because mammalian cells contain similar to 300 copies of the rDNA gene per genome, rDNA could be used to monitor CPT-induced DNA cleavage in different cell lines and possibly in tumor samples. C1 NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 34 TC 21 Z9 21 U1 0 U2 0 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 OCT 15 PY 1997 VL 25 IS 20 BP 4111 EP 4116 DI 10.1093/nar/25.20.4111 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YC609 UT WOS:A1997YC60900024 PM 9321666 ER PT J AU Cheatham, TE Kollman, PA AF Cheatham, TE Kollman, PA TI Insight into the stabilization of A-DNA by specific ion association: spontaneous B-DNA to A-DNA transitions observed in molecular dynamics simulations of d[ACCCGCGGGT](2) in the presence of hexaamminecobalt(III) SO STRUCTURE LA English DT Article DE A-DNA; hexaamminecobalt(III); hydration; ion association; molecular dynamics ID MESH EWALD METHOD; CRYSTAL-STRUCTURE; NUCLEIC-ACIDS; DOUBLE HELIX; AQUEOUS-SOLUTION; TATA-BOX; BINDING; PROTEINS; CONFORMATION; PARAMETERS AB Background: Duplex DNA is more than a simple information carrier. The sequence-dependent structure and its inherent deformability, in concert with the subtle modulating effects of the environment, play a crucial role in the regulation and packaging of DNA. Recent advances in force field and simulation methodologies allow molecular dynamics simulations to now represent the specific effects of the environment. An understanding of the environmental dependence of DNA structure gives insight into how histones are able to package DNA, how various proteins are able to bind and modulate nucleic acid structure and will ultimately aid the design of molecules to package DNA for more effective gene therapy. Results: Molecular dynamics simulations of d[ACCCGCGGGT](2) in solution in the presence of hexaamminecobalt(III) [Co(NH3)(6)(3+)] show stabilization of A-DNA and spontaneous B-DNA to A-DNA transitions, which is consistent with experimental results from NMR and Raman spectroscopic and X-ray crystallographic studies. In the absence of Co(NH3)(6)(3+), A-DNA to B-DNA transitions are observed instead. In addition to their interaction with the guanines in the major groove, Co(NH3)(6)(3+) ions bridge opposing strands in the bend across the major groove, probably stabilizing A-DNA. Conclusions: The simulation methods and force fields have advanced to a sufficient level that some representation of the environment can be seen in nanosecond length molecular dynamics simulations. These simulations suggest that, in addition to the general explanation of A-DNA stabilization by dehydration, hydration and ion association in the major groove stabilize A-DNA. C1 UNIV CALIF SAN FRANCISCO,DEPT PHARMACEUT CHEM,SAN FRANCISCO,CA 94143. NIH,STRUCT BIOL LAB,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. FU NCI NIH HHS [CA-25644]; NIGMS NIH HHS [GM08388] NR 50 TC 81 Z9 86 U1 1 U2 7 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0969-2126 J9 STRUCTURE JI Structure PD OCT 15 PY 1997 VL 5 IS 10 BP 1297 EP 1311 DI 10.1016/S0969-2126(97)00282-7 PG 15 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA YF024 UT WOS:A1997YF02400007 PM 9351805 ER PT J AU Jing, NJ Rando, RF Pommier, Y Hogan, ME AF Jing, NJ Rando, RF Pommier, Y Hogan, ME TI Ion selective folding of loop domains in a potent anti-HIV oligonucleotide SO BIOCHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; DNA APTAMER; TELOMERIC DNA; THROMBIN; INHIBITION; GUANOSINE; COMPLEXES; D(GGTTGGTGTGGTTGG); TETRAPLEX; INTEGRASE AB Previously, we have described inhibition of HIV-1 infection by T30177, 5'-(GTGGTGGGTGGGTGGGT)-3', an oligonucleotide that is a potent inhibitor of HIV-1 integrase in vitro (Mazumder et al. (1996) Biochemistry 35, 13762). Here a family of oligonucleotides, analogs of T30177, has been studied. On the basis of thermal denaturation, we show that a folded structure of T30177 is much more stable than that of the thrombin binding aptamer, which only differs with T30177 in the loop sequence. Sequence changes reveal that loop interactions are solely responsible for this observed stability difference. In the presence of K+ ion, the fold of T30695, a designed 16mer derivative, is indeed more stable than T30177. Loop folding within T30695 is very ion selective. Quantitative analysis of thermal denaturation suggests that the loops of T30695, 5'-(GGGTGGGTGGGTGGGT)-3', and T30177 confer the ability to coordinate three equivalents of K+ ion (one bound to the core octet and two bound to the loops); however, the thrombin binding aptamer is shown to bind only one K+ equivalent. Folding kinetics and CD titration demonstrate that K+-induced folding of T30695 and T30177 is a two-step process, consistent with a sequential model in which a first equivalent of K+ binds to the octet core, followed by slow K+-induced rearrangement of the loop domains. Comparing structural stability with the capacity of the folded oligomers to inhibit the HIV-1 integrase enzyme in vitro or HIV-I infection in cell culture, we have found that the folding and activity data are highly correlated, suggesting that formation of an orderly, ion-coordinated loop structure similar to that in T30177 or T30695 may be a prerequisite for both integrase inhibition and anti-HIV-l activity. C1 BAYLOR COLL MED,DEPT PHYSIOL & MOL BIOPHYS,HOUSTON,TX 77030. ARONEX PHARMACEUT CORP,THE WOODLANDS,TX 77380. NCI,MOL PHARMACOL LAB,DIV BASIC SCI,BETHESDA,MD 20892. FU NHLBI NIH HHS [2T32-HL07676]; NIAID NIH HHS [R43AI37332] NR 31 TC 114 Z9 117 U1 0 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 14 PY 1997 VL 36 IS 41 BP 12498 EP 12505 DI 10.1021/bi962798y PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YB019 UT WOS:A1997YB01900013 PM 9376354 ER PT J AU Wu, JQ Ozarowski, A Maki, AH Urbaneja, MA Henderson, LE CasasFinet, JR AF Wu, JQ Ozarowski, A Maki, AH Urbaneja, MA Henderson, LE CasasFinet, JR TI Binding of the nucleocapsid protein of type 1 human immunodeficiency virus to nucleic acids studied using phosphorescence and optically detected magnetic resonance SO BIOCHEMISTRY LA English DT Article ID SINGLE-STRANDED POLYNUCLEOTIDES; PHOTOEXCITED TRIPLET-STATES; ZINC-FINGER; IONIZATION-POTENTIALS; TRYPTOPHAN RESIDUES; GENOMIC RNA; DNA; HIV-1; RETROVIRUSES; ODMR AB The binding of p7 nucleocapsid protein of type 1 human immunodeficiency virus (HIV-I) to various oligonucleotides and polynucleotides has been investigated by phosphorescence and optically detected magnetic resonance (ODMR) spectroscopy, The intrinsic spectroscopic probe used in these studies is the photoexcited triplet state of Trp37, which is associated with the C-terminal zinc finger of p7 and is its only tryptophan residue. Complex formation produces a red-shift of the phosphorescence 0,0-band (Delta E-0,E-0) of Trp37 as well as a reduction of the zero field splitting (zfs) D parameter. Increases of -Delta E-0,E-0 (A < C < U < G < I) rank with increasing binding affinity to nucleic acid homooligomers (A similar to C < U < G similar to I). It is proposed that the magnitude of the shift reflects the extent of aromatic stacking interactions. We propose also that -Delta D increases not only with increased aromatic stacking but also with the extent of charge transfer (CT) character admired into the triplet state. The quantity Delta D/Delta E-0,E-0 correlates with the electron affinity of the bases (G < A < C < U approximate to T), suggesting that this quantity reflects the extent of CT character admired with the triplet state by the aromatic stacking interaction, Also affected by nucleic acid binding of p7 are the kinetic parameters of Trp37. We find a selective increase in the relative populating rate, and of the decay rate constant of the T-x sublevel. In binding of p7 to either d(IT)(2) or d(IT)(4), two distinct sets of triplet states of Trp37 are resolved, suggesting the existence of specific nucleic acid binding modes of these heterooligomers. C1 UNIV CALIF DAVIS, DEPT CHEM, DAVIS, CA 95616 USA. NCI, FREDERICK CANC RES & DEV CTR, AIDS VACCINE PROGRAM, SAIC FREDERICK, FREDERICK, MD 21702 USA. FU NIEHS NIH HHS [ES-02662] NR 58 TC 27 Z9 27 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 14 PY 1997 VL 36 IS 41 BP 12506 EP 12518 DI 10.1021/bi970676f PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YB019 UT WOS:A1997YB01900014 PM 9376355 ER PT J AU Moitra, J Szilak, L Krylov, D Vinson, C AF Moitra, J Szilak, L Krylov, D Vinson, C TI Leucine is the most stabilizing aliphatic amino acid in the d position of a dimeric leucine zipper coiled coil SO BIOCHEMISTRY LA English DT Article ID SYNTHETIC MODEL PROTEINS; TRANSCRIPTION FACTOR; CRYSTAL-STRUCTURE; SIDE-CHAINS; DNA-BINDING; ALPHA-HELICES; BASIC REGION; GCN4; SPECIFICITY; EXPRESSION AB The energetic contribution of seven amino acids in the d position of a dimeric leucine zipper coiled coil structure was measured by determining the thermal stability. The d position contains the conserved leucines found in the leucine zipper. We used a natural bZIP protein as our host-guest system that remains dimeric when a single d position is mutated. We have determined the thermal stability, monitored by circular dichroism, of 14 proteins which indicate that alanine is 4.6 kcal mol(-1) per residue less stabilizing than leucine. The similarly sized amino acid isoleucine is 2.9 kcal mol(-1) per residue less stabilizing than leucine, suggesting that leucine is well-packed. Model building indicates that the beta-branched amino acids isoleucine and valine in the d position produced interhelical clashes between the C gamma 2 methyl groups when placed in the favored rotamer conformation. The stabilization by leucine in different d positions is context-dependent; it varies by over 2 kcal mol(-1) in the two positions examined. The order of stabilization is L, M, I, V, C, A, and S. Cysteine in the d position can form a disulfide bond which stabilizes the coiled coil. C1 NCI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. OI Szilak, Laszlo/0000-0003-0334-272X NR 43 TC 105 Z9 105 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 14 PY 1997 VL 36 IS 41 BP 12567 EP 12573 DI 10.1021/bi971424h PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YB019 UT WOS:A1997YB01900021 PM 9376362 ER PT J AU Yan, LJ Levine, RL Sohal, RS AF Yan, LJ Levine, RL Sohal, RS TI Oxidative damage during aging targets mitochondrial aconitase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HYDROGEN-PEROXIDE RELEASE; MUSCA-DOMESTICA; PROTEIN OXIDATION; LIFE EXPECTANCY; MAMMALIAN-CELLS; SUPEROXIDE; INCREASE; IRON; INACTIVATION; HYPEROXIA AB The mechanisms that cause aging are not well understood, The oxidative stress hypothesis proposes that the changes associated with aging are a consequence of random oxidative damage to biomolecules. We hypothesized that oxidation of specific proteins is critical in controlling the rate of the aging process, Utilizing an immunochemical probe for oxidatively modified proteins, we show that mitochondrial aconitase, an enzyme in the citric acid cycle, is a specific target during aging of the housefly, The oxidative damage detected immunochemically was paralleled by a loss of catalytic activity of aconitase, an enzyme activity that is critical in energy metabolism. Experimental manipulations which decrease aconitase activity should therefore cause a decrease in life-span, This expected decrease was observed when flies were exposed to hyperoxia, which oxidizes aconitase, and when they were given fluoroacetate, an inhibitor of aconitase, The identification of a specific target of oxidative damage during aging allows for the assessment of the physiological age of a specific individual and provides a method for the evaluation of treatments designed to affect the aging process. C1 SO METHODIST UNIV,DEPT BIOL SCI,DALLAS,TX 75275. NHLBI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. RI Levine, Rodney/D-9885-2011 FU NIA NIH HHS [R01 AG007657, R01 AG013563, R01AG13563, R01AG7657] NR 51 TC 409 Z9 417 U1 2 U2 14 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 OCT 14 PY 1997 VL 94 IS 21 BP 11168 EP 11172 DI 10.1073/pnas.94.21.11168 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YA930 UT WOS:A1997YA93000019 PM 9326580 ER PT J AU Lin, KM Wang, SW Julius, MA Kitajewski, J Moos, M Luyten, FP AF Lin, KM Wang, SW Julius, MA Kitajewski, J Moos, M Luyten, FP TI The cysteine-rich frizzled domain of Frzb-1 is required and sufficient for modulation of Wnt signaling SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CELL LUNG-CARCINOMA; XENOPUS EMBRYOS; EXPRESSION; PROTEINS; FAMILY; GENES; AXIS AB Convincing evidence has accumulated to identify the Frizzled proteins as receptors for the Wnt growth factors, In parallel, a number of secreted frizzled-like proteins with a conserved N-terminal frizzled motif have been identified, One of these proteins, Frzb-1, binds Wnt-1 and Xwnt-8 proteins and antagonizes Xwnt-8 signaling in Xenopus embryos, Here we report that Frzb-1 blocks Wnt-1 induced cytosolic accumulation of beta-catenin, a key component of the Wnt signaling pathway, in human embryonic kidney cells, Structure/function analysis reveals that complete removal of the frizzled domain of Frzb-1 abolishes the Wnt-1/Frzb-1 protein interaction and the inhibition of Wnt-1 mediated axis duplication in Xenopus embryos, In contrast, removal of the C-terminal portion of the molecule preserves both Frzb-Wnt binding and functional inhibition of Wnt signaling, Partial deletions of the Frzb-1 cysteine-rich domain maintain Wnt-1 interaction, but functional inhibition is lost. Taken together, these findings support the conclusion that the frizzled domain is necessary and sufficient for both activities, Interestingly, Frzb-1 does not block Wnt-5A signaling in a Xenopus functional assay, even though Wnt-5A coimmunoprecipitates with Frzb-1, suggesting that coimmunoprecipitation does not necessarily imply inhibition of Wnt function. C1 NIDR,CRANIOFACIAL & SKELETAL DIS BRANCH,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL & EVALUAT,DEV BIOL LAB,BETHESDA,MD 20892. COLUMBIA UNIV COLL PHYS & SURG,DEPT PATHOL,NEW YORK,NY 10032. COLUMBIA UNIV COLL PHYS & SURG,CTR REPROD SCI,NEW YORK,NY 10032. RI Moos, Malcolm/F-3673-2011; OI Moos, Malcolm/0000-0002-9575-9938; Wang, Shouwen/0000-0001-8484-1795 NR 28 TC 161 Z9 165 U1 1 U2 6 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 OCT 14 PY 1997 VL 94 IS 21 BP 11196 EP 11200 DI 10.1073/pnas.94.21.11196 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YA930 UT WOS:A1997YA93000024 PM 9326585 ER PT J AU Minucci, S Horn, V Bhattacharyya, N Russanova, V Ogryzko, VV Gabriele, L Howard, BH Ozato, K AF Minucci, S Horn, V Bhattacharyya, N Russanova, V Ogryzko, VV Gabriele, L Howard, BH Ozato, K TI A histone deacetylase inhibitor potentiates retinoid receptor action in embryonal carcinoma cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TUMOR VIRUS PROMOTER; TRANSCRIPTIONAL ACTIVATION; NUCLEOSOMAL DNA; ACETYLATION; CHROMATIN; DISRUPTION; APOPTOSIS; TRAPOXIN; LIGANDS; PROTEIN AB Histone acetylation is thought to have a role in transcription, To gain insight into the role of histone acetylation in retinoid-dependent transcription, we studied the effects of trichostatin A (TSA), a specific inhibitor of histone deacetylase, on P19 embryonal carcinoma cells, We show that coaddition of TSA and retinoic acid (RA) markedly enhances neuronal differentiation in these cells, although TSA alone does not induce differentiation but causes extensive apoptosis, Consistent with the cooperative effect of TSA and RA, coaddition of the two agents synergistically enhanced transcription from stably integrated RA-responsive promoters, The transcriptional synergy by TSA and RA required the RA-responsive element and a functional retinoid X receptor (RXR)/retinoic acid receptor (RAR) heterodimer, both obligatory for RA-dependent transcription, Furthermore, TSA led to promoter activation by an RXR-selective ligand that was otherwise inactive in transcription, In addition, TSA enhanced transcription from a minimum basal promoter, independently of the RA-responsive element, Finally, we show that TSA alone or in combination with RA increases in vivo endonuclease sensitivity within the RA-responsive promoter, suggesting that TSA treatment might alter a local chromatin environment to enhance RXR/RAR heterodimer action, Thus, these results indicate that histone acetylation influences activity of the heterodimer, which is in line with the observed interaction between the RXR/RAR heterodimer and a histone acetylase presented elsewhere. C1 NICHHD,LAB MOL GROWTH REGULAT,NIH,BETHESDA,MD 20892. NIAID,IMMUNOPATHOL LAB,NIH,BETHESDA,MD 20892. RI Minucci, Saverio/J-9669-2012; Ogryzko, Vasily/M-6665-2015 OI Ogryzko, Vasily/0000-0002-8548-1389 NR 41 TC 90 Z9 91 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 OCT 14 PY 1997 VL 94 IS 21 BP 11295 EP 11300 DI 10.1073/pnas.94.21.11295 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YA930 UT WOS:A1997YA93000042 PM 9326603 ER PT J AU Leikin, S Parsegian, VA Yang, WH Walrafen, GE AF Leikin, S Parsegian, VA Yang, WH Walrafen, GE TI Raman spectral evidence for hydration forces between collagen triple helices SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID X-RAY-DIFFRACTION; WATER-STRUCTURE; LIQUID WATER; DEPENDENCE; PEPTIDE; TENDON AB Hydration forces are thought to result from the energetic cost of water rearrangement near macromolecular surfaces, Raman spectra, collected on the same collagen samples on which these forces were measured, reveal a continuous change in water hydrogen-bonding structure as a function of separation between collagen triple helices. The varying spectral parameters track the force-distance curve. The energetic cost of water ''restructuring,'' estimated from the spectra, Is consistent with the measured energy of intermolecular interaction, These correlations support the idea that the change in water structure underlies the exponentially varying forces seen in this system at least over the 13-18-Angstrom range of interaxial separations. C1 NICHHD,NIH,BETHESDA,MD 20892. HOWARD UNIV,DEPT CHEM,WASHINGTON,DC 20059. RP Leikin, S (reprint author), NICHHD,DIV COMP RES & TECHNOL,BETHESDA,MD 20892, USA. RI Leikin, Sergey/A-5518-2008 OI Leikin, Sergey/0000-0001-7095-0739 NR 31 TC 107 Z9 108 U1 1 U2 23 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 OCT 14 PY 1997 VL 94 IS 21 BP 11312 EP 11317 DI 10.1073/pnas.94.21.11312 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YA930 UT WOS:A1997YA93000045 PM 9326606 ER PT J AU Jeffers, M Schmidt, L Nakaigawa, N Webb, CP Weirich, G Kishida, T Zbar, B VandeWoude, GF AF Jeffers, M Schmidt, L Nakaigawa, N Webb, CP Weirich, G Kishida, T Zbar, B VandeWoude, GF TI Activating mutations for the Met tyrosine kinase receptor in human cancer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; SCATTER FACTOR; EPITHELIAL-CELLS; FACTOR/SCATTER FACTOR; PROTOONCOGENE PRODUCT; TRANSFORMING GENE; TUMORIGENICITY; EXPRESSION; IDENTIFICATION; INDUCTION AB Recently, mutations in the Met tyrosine kinase receptor have been identified in both hereditary and sporadic forms of papillary renal carcinoma. We have introduced the corresponding mutations into the met cDNA and examined the effect of each mutation in biochemical and biological assays. We find that the Met mutants exhibit increased levels of tyrosine phosphorylation and enhanced kinase activity toward an exogenous substrate when compared with wild-type Met. Moreover, NIH 3T3 cells expressing mutant Met molecules form foci in vitro and are tumorigenic in nude mice. Enzymatic and biological differences were evident among the various mutants examined, and the somatic mutations were generally more active than those of germ-line origin. A strong correlation between the enzymatic and biological activity of the mutants was observed, indicating that tumorigenesis by Met is quantitatively related to its level of activation. These results demonstrate that the Met mutants originally identified in human papillary renal carcinoma are oncogenic and thus are likely to play a determinant role in this disease, and these results raise the possibility that activating Met mutations also may contribute to other human malignancies. C1 NCI,FREDERICK CANC RES & DEV CTR,ADV BIOSCI LABS,BASIC RES PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21702. SCI APPLICAT INT CORP,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD 21702. YOKOHAMA CITY UNIV,SCH MED,DEPT UROL,KANAZAWA KU,YOKOHAMA,KANAGAWA 236,JAPAN. RI Webb, Craig/I-8123-2012 NR 55 TC 312 Z9 314 U1 0 U2 6 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 OCT 14 PY 1997 VL 94 IS 21 BP 11445 EP 11450 DI 10.1073/pnas.94.21.11445 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YA930 UT WOS:A1997YA93000068 PM 9326629 ER PT J AU Zimonjic, DB Kelley, MJ Rubin, JS Aaronson, SA Popescu, NC AF Zimonjic, DB Kelley, MJ Rubin, JS Aaronson, SA Popescu, NC TI Fluorescence in situ hybridization analysis of keratinocyte growth factor gene amplification and dispersion in evolution of great apes and humans SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN CHROMOSOME-2; ALPHA-SATELLITES; DNA; LOCALIZATION; EMERGENCE; SEQUENCES; ORIGIN AB Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor family. Portions of the gene encoding KGF were amplified during primate evolution and are present in multiple nonprocessed copies in the human genome, Nucleotide analysis of a representative sampling of these KGF-like sequences indicated that they were at least 95% identical to corresponding regions of the KGF gene, To localize these sequences to specific chromosomal sites in human and higher primates, we used fluorescence in situ hybridization, In human, using a cosmid probe encoding KGF exon 1, we assigned the location of the KGF gene to chromosome 15q15-21.1. In addition, copies of KGF-like sequences hybridizing only with a cosmid probe encoding exons 2 and 3 were localized to dispersed sites on chromosome 2q21, 9p11, 9q12-13, 18p11, 18q11, 21q11, and 21q21.1. The distribution of KGF-like sequences suggests a role for alphoid DNA in their amplification and dispersion, In chimpanzee, KGF-like sequences were observed at five chromosomal sites, which were each homologous to sites in human, while in gorilla, a subset of four of these homologous sites was identified; in orangutan two sites were identified, while gibbon exhibited only a single site. The chromosomal localization of KGF sequences in human and great ape genomes indicates that amplification and dispersion occurred in multiple discrete steps, with initial KGF gene duplication and dispersion taking place in gibbon and involving loci corresponding to human chromosomes 15 and 21. These findings support the concept of a closer evolutionary relationship of human and chimpanzee and a possible selective pressure for such dispersion during the evolution of higher primates. C1 NCI,EXPT CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,USN,MED ONCOL BRANCH,BETHESDA,MD 20889. NCI,CELLULAR & MOL BIOL LAB,BETHESDA,MD 20892. MT SINAI MED CTR,RUTTENBERG CANC CTR,NEW YORK,NY 10029. OI Kelley, Michael/0000-0001-9523-6080 NR 21 TC 44 Z9 46 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 OCT 14 PY 1997 VL 94 IS 21 BP 11461 EP 11465 DI 10.1073/pnas.94.21.11461 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YA930 UT WOS:A1997YA93000071 PM 9326632 ER PT J AU Derbyshire, V Wood, DW Wu, W Dansereau, JT Dalgaard, JZ Belfort, M AF Derbyshire, V Wood, DW Wu, W Dansereau, JT Dalgaard, JZ Belfort, M TI Genetic definition of a protein-splicing domain: Functional mini-inteins support structure predictions and a model for intein evolution SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GROUP-II INTRONS; SELECTIVE ADVANTAGE; ENDONUCLEASES; ELEMENTS; SEQUENCE; CLEAVAGE; CONFERS; FAMILY; MOTIF; RNA AB Inteins are protein-splicing elements, most of which contain conserved sequence blocks that define a family of homing endonucleases. Like group I introns that encode such endonucleases, inteins are mobile genetic elements. Recent crystallography and computer modeling studies suggest that inteins consist of two structural domains that correspond to the endonuclease and the protein-splicing elements. To determine whether the bipartite structure of inteins is mirrored by the functional independence of the protein-splicing domain, the entire endonuclease component was deleted from the Mycobacterium tuberculosis recA intein. Guided by computer modeling studies, and taking advantage of genetic systems designed to monitor intein function, the 440-aa Mtu recA intein was reduced to a functional mini-intein of 137 aa. The accuracy of splicing of several mini-inteins was verified. This work not only substantiates structure predictions for intein function but also supports the hypothesis that, like group I introns, mobile inteins arose by an endonuclease gene invading a sequence encoding a small, functional splicing element. C1 SUNY ALBANY,SCH PUBL HLTH,ALBANY,NY 12201. NEW YORK STATE DEPT HLTH,WADSWORTH CTR,MOL GENET PROGRAM,ALBANY,NY 12237. RENSSELAER POLYTECH INST,ISERMANN DEPT CHEM ENGN,TROY,NY 12180. NCI,FREDERICK CANC RES & DEV CTR,ADV BIOSCI LABS,BASIC RES PROGRAM,FREDERICK,MD 21701. RI Wood, David/B-2992-2012; OI Belfort, Marlene/0000-0002-1592-5618 FU NIGMS NIH HHS [R01 GM044844, R01 GM039422, R37 GM039422, GM39422, GM44844] NR 30 TC 97 Z9 101 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 OCT 14 PY 1997 VL 94 IS 21 BP 11466 EP 11471 DI 10.1073/pnas.94.21.11466 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YA930 UT WOS:A1997YA93000072 PM 9326633 ER PT J AU Woodage, T Basrai, MA Baxevanis, AD Hieter, P Collins, FS AF Woodage, T Basrai, MA Baxevanis, AD Hieter, P Collins, FS TI Characterization of the CHD family of proteins SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SACCHAROMYCES-CEREVISIAE; DNA-BINDING; MI-2 AUTOANTIGEN; YEAST; DERMATOMYOSITIS; PLANTS; FINGER AB The murine gene CHD1 (MmCHD1) was previously isolated in a search for proteins that bound a DNA promoter element. The presence of chrome (chromatin organization modifier) domains and an SNF2-related helicase/ATPase domain led to speculation that this gene regulated chromatin structure or gene transcription. This study describes the cloning and characterization of three novel human genes related to MmCHD1. Examination of sequence databases produced several more related genes, most of which were not known to be similar to MmCHD1, yielding a total of 12 highly conserved CHD genes from organisms as diverse as yeast and mammals. The major region of sequence variation is in the C-terminal part of the protein, a region with DNA-binding activity in MmCHD1. Targeted deletion of SsCHD1, the sole Saccharomyces cerevesiae CHD gene, was performed with deletion strains being less sensitive than wild type to the cytotoxic effect of 6-azauracil. This finding suggested that enhanced transcriptional arrest at RNA polymerase II pause sites due to 6-azauracil-induced nucleotide poor depletion was reduced in the deletion strain and that ScCHD1 inhibited transcription. This observation, along with the known roles of other proteins with chrome or SNF2-related helicase/ATPase domains, suggests that alteration of gene expression by CHD genes might occur by modifications of chromatin structure, with altered access of the transcriptional apparatus to its chromosomal DNA template. C1 NIH,NATL HUMAN GENOME RES INST,GENOME TECHNOL BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT MOL BIOL & GENET,BALTIMORE,MD 21205. RP Woodage, T (reprint author), NIH,NATL HUMAN GENOME RES INST,LAB GENE TRANSFER,BLDG 49,ROOM 3A14,49 CONVENT DR,MSC 4442,BETHESDA,MD 20892, USA. NR 32 TC 239 Z9 248 U1 2 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 14 PY 1997 VL 94 IS 21 BP 11472 EP 11477 DI 10.1073/pnas.94.21.11472 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YA930 UT WOS:A1997YA93000073 PM 9326634 ER PT J AU Noguchi, M Sarin, A Aman, MJ Nakajima, H Shores, EW Henkart, PA Leonard, WJ AF Noguchi, M Sarin, A Aman, MJ Nakajima, H Shores, EW Henkart, PA Leonard, WJ TI Functional cleavage of the common cytokine receptor gamma chain (gamma(c)) by calpain SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID T-CELL RECEPTOR; SEVERE COMBINED IMMUNODEFICIENCY; INTERLEUKIN-2 IL-2 RECEPTOR; HUMAN MEDULLARY THYMOCYTES; BETA-CHAIN; LYMPHOID DEVELOPMENT; CYTOPLASMIC DOMAINS; NEGATIVE SELECTION; BCL-2 EXPRESSION; INTERFERON-GAMMA AB The small subunit of calpain, a calcium-dependent cysteine protease, was found to interact with the cytoplasmic domain of the common cytokine receptor gamma chain (gamma(c)) in a yeast tno-hybrid interaction trap assay. This interaction was functional as demonstrated by the ability of calpain to cleave in vitro translated wild-type gamma(c), but not gamma(c) containing a mutation in the PEST (proline, glutamate, serine, and threonine) sequence in its cytoplasmic domain, as well as by the ability of endogenous calpain to mediate cleavage of gamma(c) in a calcium-dependent fashion. in T cell receptor-stimulated murine thymocytes, calpain inhibitors decreased cleavage of gamma(c). Moreover, in single positive CD4(+) thymocytes, not only did a calpain inhibitor augment CD3-induced proliferation, but antibodies to ye blocked this effect, Finally, treatment of cells with ionomycin could inhibit interleukin 2-induced STAT protein activation, but this inhibition could be reversed by calpain inhibitors. Together, these data suggest that calpain-mediated cleavage of gamma(c) represents a mechanism by which gamma(c)-dependent signaling can be controlled. C1 NHLBI,LAB MOL IMMUNOL,NIH,BETHESDA,MD 20892. NCI,EXPT IMMUNOL BRANCH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. NR 67 TC 62 Z9 62 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 OCT 14 PY 1997 VL 94 IS 21 BP 11534 EP 11539 DI 10.1073/pnas.94.21.11534 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YA930 UT WOS:A1997YA93000083 PM 9326644 ER PT J AU Boyer, GS Templin, DW Bowler, A Lawrence, RC Everett, DF Heyse, SP CornoniHuntley, J Goring, WP AF Boyer, GS Templin, DW Bowler, A Lawrence, RC Everett, DF Heyse, SP CornoniHuntley, J Goring, WP TI A comparison of patients with spondyloarthropathy seen in specialty clinics with those identified in a communitywide epidemiologic study - Has the classic case misled us? SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ANKYLOSING-SPONDYLITIS; RHEUMATOID-ARTHRITIS; ESKIMO POPULATION; WOMEN; MEN; PREVALENCE; CRITERIA; CLASSIFICATION; DISEASES AB Background: Undiagnosed cases of seronegative spondyloarthropathy (Spa) are often observed during epidemiologic studies. Objective: To determine the extent of and the reasons for the underdiagnosis of Spa. Methods: We studied 2 groups of Alaskan native patients with Spa using a standardized protocol that included an interview, physical examination, medical record review, and radiographic and laboratory examinations, One group consisted of patients identified in a communitywide epidemiologic study; the other group consisted of patients from related but geographically separate populations who had been diagnosed by a specialist in the hospital or a specialty clinic. All cases met the current classification criteria for Spa. The clinical and demographic features of the cases in the 2 groups were compared. Results: Fifty-five (72%) of the 76 community cases that we identified in the epidemiologic study had not been diagnosed previously as Spa. Among the undiagnosed pa tients were 34 (94%) of the 36 women, 11 (65%) of the 17 patients with ankylosing spondylitis, 12 (36%) of the 33 patients with reactive arthritis, and 24 (100%) of those with undifferentiated Spa. The community and specialty clinic patient groups were similar in age of onset of joint and back pain and in overall symptoms. The specialty clinic group had a higher proportion of men, more severe disease, and a higher frequency of iritis. Conclusions: The diagnosis of Spa was missed more often than not in the primary care setting, probably because most of the cases were of mild or moderate severity and did not fit the classic descriptions of spondyloarthropathic disorders. The higher proportion of men among the specialty clinic cases probably reflects provider expectation as well as a slightly milder disease course in women. C1 ALASKA AREA NATIVE HLTH SERV,ANCHORAGE,AK. NIAMSD,DIV EPIDEMIOL,BETHESDA,MD 20892. NEI,BETHESDA,MD 20892. NIAID,BETHESDA,MD 20892. DUKE UNIV,DEPT PUBL HLTH,DURHAM,NC. UNIV ARIZONA,OFF VICE PRESIDENT RES,TUCSON,AZ. FU NIAMS NIH HHS [Y02-AR-00005] NR 34 TC 33 Z9 33 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT 13 PY 1997 VL 157 IS 18 BP 2111 EP 2117 DI 10.1001/archinte.157.18.2111 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA YA442 UT WOS:A1997YA44200013 PM 9382668 ER PT J AU Zauderer, M Singer, A AF Zauderer, M Singer, A TI Limiting dilution analysis of primary cytotoxic T-cell precursors SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE cytotoxic T-cell; XTT assay; limiting dilution analysis ID COLORIMETRIC ASSAY; SELECTION; PROLIFERATION AB An efficient colorimetric assay has been adapted for limiting dilution analysis of cytotoxic T-cell precursors. Application of this assay in a suitable experimental model of thymic education could be especially useful in identifying factors that shape the CD8 T-cell repertoire. The essential elements of such a model are described here and elsewhere. (C) 1997 Elsevier Science B.V. C1 NCI,EXPT IMMUNOL BRANCH,BETHESDA,MD 20892. RP Zauderer, M (reprint author), UNIV ROCHESTER,MED CTR,CTR CANC,BOX 704,ROCHESTER,NY 14642, USA. FU NIA NIH HHS [AG 08179]; NIAID NIH HHS [AI 37752] NR 7 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD OCT 13 PY 1997 VL 208 IS 1 BP 85 EP 90 DI 10.1016/S0022-1759(97)00131-2 PG 6 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA YK994 UT WOS:A1997YK99400009 PM 9433464 ER PT J AU Kawamura, M Kopin, IJ Kador, PF Sato, S Tjurmina, O Eisenhofer, G AF Kawamura, M Kopin, IJ Kador, PF Sato, S Tjurmina, O Eisenhofer, G TI Effects of aldehyde/aldose reductase inhibition on neuronal metabolism of norepinephrine SO JOURNAL OF THE AUTONOMIC NERVOUS SYSTEM LA English DT Article DE aldehyde reductase; 3,4-dihydroxymandelic acid; 3,4-dihydroxyphenylglycol; norepinephrine; sympathetic nervous system; monoamine oxidase ID PERFORMANCE LIQUID-CHROMATOGRAPHY; PLASMA; CATECHOLAMINES; 3-METHOXY-4-HYDROXYPHENYLGLYCOL; 3,4-DIHYDROXYPHENYLGLYCOL; DHPG; RATS AB After norepinephrine (NE) is deaminated by monoamine oxidase (MAO), the aldehyde formed is either metabolized to 3,4-dihydroxymandelic acid (DHMA) by aldehyde dehydrogenase or is converted to 3,4-dihydroxyphenylglycol (DHPG) by aldehyde or aldose reductase. The present study examined the effects of inhibition of aldehyde and aldose reductase on production of DHPG and DHMA in rats. Mean (+/-S.E.) baseline plasma concentrations of DHPG (4.73 +/- 0.21 pmol/ml) were 60-fold higher than those of DHMA (0.08 +/- 0.01 pmol/ml). Inhibition of aldose and aldehyde reductase reduced plasma DHPG concentrations to 1.88 +/- 0.14 pmol/ml and increased plasma DHMA to 4.43 +/- 0.29 pmol/ml; additional inhibition of MAO reduced plasma DHPG to 0.16 +/- 0.06 pmol/ml and DHMA to 0.19 +/- 0.02 pmol/ml. Inhibition of aldehyde and aldose reductase also increased brain tissue levels of DHMA from 8 +/- 2 to 384 +/- 47 pmol/g and decreased levels of DHPG from 70 +/- 9 to 44 +/- 5 pmol/g. The results show that DHMA is normally a minor metabolite of NE, but becomes a major metabolite after aldehyde/aldose reductase inhibition. Published by Elsevier Science B.V. C1 NINCDS,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. NEI,LAB OCULAR THERAPUT,NIH,BETHESDA,MD 20892. NR 16 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-1838 J9 J AUTONOM NERV SYST JI J. Auton. Nerv. Syst. PD OCT 13 PY 1997 VL 66 IS 3 BP 145 EP 148 DI 10.1016/S0165-1838(97)00086-6 PG 4 WC Neurosciences SC Neurosciences & Neurology GA YF955 UT WOS:A1997YF95500005 PM 9406118 ER PT J AU Derse, D Mikovits, J Ruscetti, F AF Derse, D Mikovits, J Ruscetti, F TI X-I and X-II open reading frames of HTLV-I are not required for virus replication or for immortalization of primary T-cells in vitro SO VIROLOGY LA English DT Article ID HUMAN-ENDOTHELIAL CELLS; BOVINE LEUKEMIA-VIRUS; LONG TERMINAL REPEAT; MESSENGER-RNAS; PX REGION; VIRAL REPLICATION; MOLECULAR CLONE; LYMPHOMA VIRUS; EXPRESSION; INFECTION AB In contrast to other retroviruses of the oncovirinae subgroup, the primate and bovine leukemia viruses (HTLV, STLV, and BLV) encode genes in the X-region of the genome, between the env gene and the 3' long terminal repeat. In HTLV-I, two overlapping open reading frames (ORFs) in the distal half of the X-region encode tax and rex genes, while two ORFs (X-I and X-II) in the proximal half of this region potentially encode proteins designated p12(XI) (or roil and p30(XII) (or tof). The biological functions and mechanisms of tax and rex have been studied extensively whereas the roles of the other ORFs have not yet been established. To identify possible functions for ORFs X-I and X-II, an infectious molecular clone of HTLV-I and a mutant provirus lacking these ORFs were compared with respect to virus replication, gene expression, and ability to immortalize primary T-cells. When transiently transfected into 293 cells, both intact and deleted proviruses directed the synthesis of virus mRNAs and proteins that were quantitatively and qualitatively identical. These viruses were also indistinguishable in their abilities to infect and replicate in DBS-FRhL cells, which are permissive for HTLV-I propagation. Immortalized T-cell lines were established after cell-free or coculture methods for infection of activated, human peripheral blood or cord blood lymphocytes with each of the cloned viruses. The growth kinetics, cytokine dependence, and cell surface markers of the infected T-cell cultures were similar for each provirus clone. Thus, ORFs X-I and X-II are not essential for virus infectivity, replication, gene expression, or T-cell immortalization in vitro. C1 NCI,FREDERICK CANC RES & DEV CTR,IRSP,SAIC,FREDERICK,MD 21702. RP Derse, D (reprint author), NCI,LAB LEUKOCYTE BIOL,DIV BASIC SCI,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-56000] NR 34 TC 78 Z9 78 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 OCT 13 PY 1997 VL 237 IS 1 BP 123 EP 128 DI 10.1006/viro.1997.8781 PG 6 WC Virology SC Virology GA YD918 UT WOS:A1997YD91800013 PM 9344914 ER PT J AU Egesten, A Dyer, KD Batten, D Domachowske, JB Rosenberg, HF AF Egesten, A Dyer, KD Batten, D Domachowske, JB Rosenberg, HF TI Ribonucleases and host defense: identification, localization and gene expression in adherent monocytes in vitro SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE ribonuclease; monocyte; gene regulation; host defense ID EOSINOPHIL-DERIVED NEUROTOXIN; AMINO-ACID-SEQUENCE; MOLECULAR-CLONING; CATIONIC PROTEIN; CDNA; FAMILY; ANGIOGENIN; INHIBITION; CELLS AB Several ribonucleases of the RNase A family function as antibacterial, anti-parasitic, and anti-viral agents. In this work, we have shown that mRNAs encoding five of the six known human ribonucleases of the RNase A family are expressed in cultured human monocytes, and that ribonucleases are released by adherent monocytes in culture. Using a polyclonal antiserum prepared against recombinant protein, we have detected one of these ribonucleases, RNase 4, in lysates of normal human peripheral blood monocytes, but not granulocytes or lymphocytes, by Western blotting. Subcellular localization by immunoelectron microscopy demonstrated the presence of RNase 4 in the cytoplasmic granules of isolated monocytes. Interestingly, mRNA encoding RNase 4 could not be detected in freshly isolated monocytes, emerging only after 16 h in culture, suggesting the possibility of de novo protein synthesis in association with monocyte differentiation. (C) 1997 Elsevier Science B.V. C1 NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. NR 26 TC 30 Z9 33 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD OCT 11 PY 1997 VL 1358 IS 3 BP 255 EP 260 DI 10.1016/S0167-4889(97)00081-5 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YC732 UT WOS:A1997YC73200006 PM 9366257 ER PT J AU Hori, K Hatfield, D Maldarelli, F Lee, BJ Clouse, KA AF Hori, K Hatfield, D Maldarelli, F Lee, BJ Clouse, KA TI Selenium supplementation suppresses tumor necrosis factor alpha-induced human immunodeficiency virus type 1 replication in vitro SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID NF-KAPPA-B; GLUTATHIONE-PEROXIDASE; CELL-LINE; SIGNAL-TRANSDUCTION; OXIDATIVE STRESS; HIV REPLICATION; GENE-EXPRESSION; ACTIVATION; INFECTION; INHIBITION AB Selenium is a nutritionally essential trace element that is important for optimal function of the immune system, It is incorporated into selenoproteins as the amino acid selenocysteine and it is known to inhibit the expression of some viruses, In this study, we show that selenium supplementation for 3 days prior to exposure to tumor necrosis factor alpha (TNF-alpha) partially suppresses the induction of human immunodeficiency virus type 1 (HIV-1) replication in both chronically infected T lymphocytic and monocytic cell lines, In acute HIV-1 infection of T lymphocytes and monocytes in the absence of exogenous TNF-alpha, the suppressive effect of selenium supplementation was not observed, However, selenium supplementation did suppress the enhancing effect of TNF-alpha on HIV-1 replication in vitro in acutely infected human monocytes, but not in T lymphocytes, Selenium supplementation also increased the activities of the selenoproteins, glutathione peroxidase (GPx) and thioredoxin reductase (TR), which serve as cellular antioxidants, Taken together, these results suggest that selenium supplementation may prove beneficial as an adjuvant therapy for AIDS through reinforcement of endogenous antioxidative systems. C1 NCI,BASIC RES LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NIAID,MOL MICROBIOL LAB,NIH,BETHESDA,MD 20892. SEOUL NATL UNIV,INST MOL BIOL & GENET,MOL GENET LAB,SEOUL 151742,SOUTH KOREA. RP Hori, K (reprint author), US FDA,CTR BIOL EVALUAT & RES HFM508,DIV CYTOKINE BIOL,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 56 TC 41 Z9 47 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 OCT 10 PY 1997 VL 13 IS 15 BP 1325 EP 1332 DI 10.1089/aid.1997.13.1325 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA YE738 UT WOS:A1997YE73800009 PM 9339849 ER PT J AU Ma, Y Ito, Y AF Ma, Y Ito, Y TI Recent advances in peptide separation by countercurrent chromatography SO ANALYTICA CHIMICA ACTA LA English DT Article DE peptides; high-speed countercurrent chromatography; pH-zone-refining countercurrent chromatography; ion-pair countercurrent chromatography ID COIL PLANET CENTRIFUGE; PURIFICATION; LIGAND; ACID AB In recent years, countercurrent chromatography (CCC) for the peptide separation has been substantially improved in terms of partition efficiency and separation time. The solvent system composed of tert-butyl methyl ether, acetonitrile and water at various volume ratios provides almost universal application for peptide separation by high speed CCC, Recently developed pH-zone-refining CCC also provides efficient separations on a preparative scale, and if used with an ion-pairing ligand it can also separate natural and synthetic peptides. (C) 1997 Elsevier Science B.V. RP Ma, Y (reprint author), NHLBI,BIOPHYS CHEM LAB,NIH,BLDG 10,ROOM 7N322,CTR DR MSC 1676,BETHESDA,MD 20892, USA. NR 35 TC 15 Z9 19 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0003-2670 J9 ANAL CHIM ACTA JI Anal. Chim. Acta PD OCT 10 PY 1997 VL 352 IS 1-3 BP 411 EP 427 DI 10.1016/S0003-2670(97)00223-7 PG 17 WC Chemistry, Analytical SC Chemistry GA YH948 UT WOS:A1997YH94800031 ER PT J AU Fasciano, J Hatzidimitriou, G Yuan, J Katz, JL Ricaurte, GA AF Fasciano, J Hatzidimitriou, G Yuan, J Katz, JL Ricaurte, GA TI N-methylation dissociates methamphetamine's neurotoxic and behavioral pharmacologic effects SO BRAIN RESEARCH LA English DT Article DE dopamine; serotonin; neurotoxicity; amphetamine ID TYROSINE-HYDROXYLASE ACTIVITY; RAT-BRAIN; SEROTONIN NEUROTOXICITY; P-CHLOROAMPHETAMINE; STRIATAL DOPAMINE; SQUIRREL-MONKEYS; METHYLAMPHETAMINE; N,N-DIMETHYLAMPHETAMINE; DEPLETION; INCREASES AB The present studies further examined the effect of N-methylation on the behavioral and neurotoxic effects of methamphetamine. Drug discrimination studies employing a training dose of 1 mg/kg of methamphetamine were used to confirm and extend previous behavioral studies indicating that N-methylation reduced the behavioral activity of methamphetamine 5- to 10-fold. In subsequent neurotoxicity studies, rats received doses of methamphetamine (10 mg/kg, s.c., every 6 h x 5) or its N-methylated derivative, N,N-dimethylamphetamine (100 mg/kg, s.c., every 6 h x 5) that, based on the results of the behavioral studies, would be expected to produce behaviorally equivalent effects. Saline-treated rats served as controls. Two weeks after treatment, the status of brain dopamine (DA) and serotonin (5-HT) neurons was assessed by measuring DA and 5-HT axon terminal markers. As anticipated, methamphetamine produced neurochemical deficits indicative of DA and 5-HT axon terminal damage. By contrast, despite the fact that it was given at a dose behaviorally equivalent to methamphetamine, N-N-dimethylamphetamine failed to produce signs of DA or 5-HT neurotoxicity. These results indicate that N-methylation dissociates methamphetamine's neurotoxic and behavioral pharmacologic effects, and suggest that it may be possible to separate the neurotoxic and pharmacologic effects of other substituted amphetamine derivatives with potentially useful clinical activity (e.g. fenfluramine and methylenedioxymethamphetamine). (C) 1997 Elsevier Science B.V. C1 JOHNS HOPKINS MED INST,DEPT NEUROL,BALTIMORE,MD 21224. NIDA,PSYCHOL SECT,ADDICT RES CTR,INTRAMURAL RES PROGRAM,BALTIMORE,MD 21224. OI Katz, Jonathan/0000-0002-1068-1159 FU NIDA NIH HHS [KO2 DA00206, R01DA06275] NR 41 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 10 PY 1997 VL 771 IS 1 BP 115 EP 120 DI 10.1016/S0006-8993(97)00801-9 PG 6 WC Neurosciences SC Neurosciences & Neurology GA YD132 UT WOS:A1997YD13200013 PM 9383014 ER PT J AU Lee, SK Malpeli, M Cancedda, R Utani, A Yamada, Y Kleinman, HK AF Lee, SK Malpeli, M Cancedda, R Utani, A Yamada, Y Kleinman, HK TI Chain expression by chick chondrocytes and mouse cartilaginous tissues in vivo and in vitro SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID BASEMENT-MEMBRANE; LAMININ; DIFFERENTIATION; COLLAGEN; CELLS; FIBRONECTIN; INVITRO; CHONDROGENESIS; LOCALIZATION; ATTACHMENT AB We have observed that laminins are expressed in the chondrocytes of chick embryo sternum, mouse limb bud, and adult mouse knee joint by the methods of in situ hybridization, immunohistochemistry, Western blotting, and immunoprecipitation. From in situ hybridization using similar sized RNA probes for different mouse laminin chains, mRNAs for the alpha 1, alpha 2, beta 1, beta 2, and gamma 1 chains were expressed in the chondrocytes of chick embryo sternum, mouse limb bud, and the articular cartilage cap and epiphyseal growth plate of adult mouse knee joint. Through the use of chain-specific antibodies, staining for laminins was observed in the cytoplasm of chondrocytes from chick embryo sternum, mouse limb bud, and adult mouse knee joint. Western blot analysis confirmed the presence of laminin chains in the cells and sternal tissues. Cultured chick embryonic sternal chondrocytes expressed laminin mRNAs in the proliferating stage (2-3 days of culture) but the level increased in the aggregated cells during the maturation stage (5-7 days of culture). Comparable data were also obtained after immunostaining the cells. Thus, laminins are expressed in significant amounts by chondrocytes and may have an important role in cartilage development. (C) 1997 Academic Press. C1 NIDR,CRANIOFACIAL DEV BIOL & REGENERAT BRANCH,NIH,BETHESDA,MD 20892. IST NAZL RIC CANC,I-16132 GENOA,ITALY. NR 42 TC 13 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD OCT 10 PY 1997 VL 236 IS 1 BP 212 EP 222 DI 10.1006/excr.1997.3710 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA YC724 UT WOS:A1997YC72400023 PM 9344601 ER PT J AU Croteau, DL Bohr, VA AF Croteau, DL Bohr, VA TI Repair of oxidative damage to nuclear and mitochondrial DNA in mammalian cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID HAMSTER OVARY CELLS; ESCHERICHIA-COLI; XERODERMA-PIGMENTOSUM; SACCHAROMYCES-CEREVISIAE; COCKAYNE-SYNDROME; ENDONUCLEASE-III; BASE DAMAGE; PYRIMIDINE DIMERS; THYMINE GLYCOL; RINR-38 CELLS RP Croteau, DL (reprint author), NIA,GENET MOL LAB,NIH,BALTIMORE,MD 21224, USA. NR 76 TC 328 Z9 337 U1 1 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 10 PY 1997 VL 272 IS 41 BP 25409 EP 25412 DI 10.1074/jbc.272.41.25409 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YA358 UT WOS:A1997YA35800001 PM 9325246 ER PT J AU Yuan, DS Dancis, A Klausner, RD AF Yuan, DS Dancis, A Klausner, RD TI Restriction of copper export in Saccharomyces cerevisiae to a late Golgi or post-Golgi compartment in the secretory pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID WILSON-DISEASE GENE; VACUOLAR H+-ATPASE; CLASS-II MOLECULES; MENKES DISEASE; CANDIDATE GENE; IRON-METABOLISM; TRANSPORTING ATPASE; PLASMA-MEMBRANE; YEAST-CELLS; FET3 GENE AB The CCC2 gene in the yeast Saccharomyces cerevisiae encodes a P-type ATPase (Ccc2p) required for the export of cytosolic copper to the extracytosolic domain of a copper dependent oxidase, Fet3p. Ccc2p appears to be both a structural and functional homolog of ATPases impaired in two human disorders of intracellular copper transport, Menkes disease and Wilson disease. In the present work, three approaches were used to determine the locus of Ccc2p-dependent copper export within the secretory pathway. First, like ccc2 mutants, sec mutants blocked in the secretory pathway at steps prior to and including the Golgi complex failed to deliver radioactive copper to Fet3p. Second, also like ccc2 mutants, vps33 and certain other mutants with defects in post-Golgi sorting exhibited phenotypes traceable to deficient copper delivery to Fet3p. These findings were sufficient to explain the respiratory deficiency of these mutants. Third, immunofluorescence microscopy revealed that Ccc2p was distributed among several punctate foci within wild-type cells, consistent with late Golgi or post-Golgi localization. Thus, copper export by Ccc2p appears to be restricted to a late or post-Golgi compartment in the secretary pathway. C1 NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892. UNIV PENN,DEPT MED,DIV HEMATOL ONCOL,PHILADELPHIA,PA 19104. NCI,OFF DIRECTOR,NIH,BETHESDA,MD 20892. NR 60 TC 119 Z9 123 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 10 PY 1997 VL 272 IS 41 BP 25787 EP 25793 DI 10.1074/jbc.272.41.25787 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YA358 UT WOS:A1997YA35800062 PM 9325307 ER PT J AU Jin, DY Teramoto, H Giam, CZ Chun, RF Gutkind, JS Jeang, KT AF Jin, DY Teramoto, H Giam, CZ Chun, RF Gutkind, JS Jeang, KT TI A human suppressor of c-Jun N-terminal kinase 1 activation by tumor necrosis factor alpha SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID T-CELL LEUKEMIA; VIRUS TYPE-I; PROTEIN-COUPLED RECEPTORS; HETEROTRIMERIC G-PROTEINS; BETA-GAMMA-SUBUNITS; MAP KINASE; SIGNAL-TRANSDUCTION; HA-RAS; TAX; PATHWAY AB Tumor necrosis factor alpha (TNF alpha) has pleiotropic effects on cellular metabolism. One of the signaling paths from the TNF alpha receptor induces a stress-activated protein kinase cascade. Components within this TNF alpha kinase cascade include mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 1 (MEKK1) and stress-activated protein kinase/extracellular signal-regulated kinase kinase (SEK), which regulate the activity of c-Jun N-terminal kinase 1 (JNK1). Currently, molecules upstream of MEKK1 that link TNF alpha receptor to downstream kinases are not well understood. Besides TNF alpha, many other stimuli including several oncoproteins can activate JNK1. In most cases, the signaling cascade(s) leading from oncoproteins to JNK1 is poorly elucidated. We report here that the human T-cell lymphotrophic virus, type I (HTLV-I) oncoprotein, Tax, can activate JNK1. We isolated a novel human cell factor, G-protein pathway suppressor 2 (GPS2), by its ability to bind the HTLV-I oncoprotein, and we show that this factor can potently suppress Tax activation of JNK1. In trying to understand the mechanism of GPS2 activity, we found that it also suppressed TNF alpha activation of JNK1 but not TNF alpha activation of p38 kinase nor phorbol activation of extracellular signal-regulated kinase 2. Because GPS2 has minimal effect on MEKK1- or SEK-regulated JNK1 activity, it could act at a point between the TNF alpha receptor and MEKK1 in the initial step(s) of this kinase cascade. Alternatively, it is not excluded that GPS2 could work in a parallel pathway that leads from TNF alpha to JNK1. GPS2 represents a new molecule that could contribute important insights toward how cytokine-and oncoprotein-mediated signal transduction might converge. C1 NIAID,MOL MICROBIOL LAB,MOL VIROL SECT,NIH,BETHESDA,MD 20892. NIDR,CELLULAR DEV & ONCOL LAB,NIH,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT MICROBIOL & IMMUNOL,BETHESDA,MD 20814. RI Chun, Rene/A-9415-2010 OI Chun, Rene/0000-0002-0190-0807 NR 42 TC 80 Z9 82 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 10 PY 1997 VL 272 IS 41 BP 25816 EP 25823 DI 10.1074/jbc.272.41.25816 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YA358 UT WOS:A1997YA35800066 PM 9325311 ER PT J AU Kaburagi, Y Satoh, S Tamemoto, H YamamotoHonda, R Tobe, K Veki, K Yamauchi, T KonoSugita, E Sekihara, H Aizawa, S Cushman, SW Akanuma, Y Yazaki, Y Kadowaki, T AF Kaburagi, Y Satoh, S Tamemoto, H YamamotoHonda, R Tobe, K Veki, K Yamauchi, T KonoSugita, E Sekihara, H Aizawa, S Cushman, SW Akanuma, Y Yazaki, Y Kadowaki, T TI Role of insulin receptor substrate-1 and pp60 in the regulation of insulin-induced glucose transport and GLUT4 translocation in primary adipocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RAT ADIPOSE-CELLS; TYROSINE-PHOSPHORYLATED PROTEIN; PHOSPHATIDYLINOSITOL 3-KINASE; HEPATOMA-CELLS; ACTIVATING PROTEIN; PLASMA-MEMBRANE; 3T3-L1 CELLS; KINASE; IRS-1; MICE AB In muscle and fat, glucose transport occurs through the translocation of GLUT4 from an intracellular pool to the cell surface. Phosphatidylinositol (PI) 3-kinase has been shown to be required in this process. Insulin is thought to activate this enzyme by stimulating its association with tyrosine-phosphorylated proteins such as insulin receptor substrate (IRS)-1, IRS-2, Grb2-associated binder-1, and pp60. To study the role of these endogenous substrates in glucose transport, we analyzed adipocytes from IRS-1 null mice that we previously generated (Tamemoto, H., Kadowaki, T., Tobe, K., Yagi, T., Sakura, H., Hayakawa, T., Terauchi, Y., Ueki, K., Kaburagi, Y., Satoh, S., Sekihara, H., Yoshioka, S., Horikoshi, H., Furuta, Y., Ikawa, Y., Kasuga, M., Yazaki Y., and Aizawa S. (1994) Nature 372, 182-186). In adipocytes from these mice, we showed that: 1) insulin-induced PI 3-kinase activity in the antiphosphotyrosine immunoprecipitates was 54% of wild-type; 2) pp60 was the major tyrosine-phosphorylated protein that associated with PI 3-kinase, whereas tyrosine phosphorylaion of IRS-2 as well as its association with this enzyme was almost undetectable; and 3) glucose transport and GLUT4 translocation at maximal insulin stimulation were decreased to 52 and 68% of those from wild-type. These data suggest that both IRS-1 and pp60 play a major role in insulin-induced glucose transport in adipocytes, and that pp60 is predominantly involved in regulating this process in the absence of IRS-1. C1 UNIV TOKYO,FAC MED,DEPT INTERNAL MED 3,BUNKYO KU,TOKYO 113,JAPAN. YOKOHAMA CITY UNIV,SCH MED,DEPT INTERNAL MED 3,KANAZAWA KU,YOKOHAMA,KANAGAWA 236,JAPAN. INST DIABET CARE & RES,ASAHI LIFE FDN,CHIYODA KU,TOKYO 100,JAPAN. NIDDK,EXPT DIABET METAB & NUTR SECT,DIABET BRANCH,NIH,BETHESDA,MD 20892. KUMAMOTO UNIV,SCH MED,IMEG,LAB MORPHOGENESIS,KUMAMOTO 860,JAPAN. NR 42 TC 77 Z9 77 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 10 PY 1997 VL 272 IS 41 BP 25839 EP 25844 DI 10.1074/jbc.272.41.25839 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YA358 UT WOS:A1997YA35800069 PM 9325314 ER PT J AU Koshiba, M Kojima, H Huang, S Apasov, S Sitkovsky, MV AF Koshiba, M Kojima, H Huang, S Apasov, S Sitkovsky, MV TI Memory of extracellular adenosine A(2A) purinergic receptor-mediated signaling in murine T cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; DEAMINASE DEFICIENCY; EFFECTOR FUNCTIONS; LYMPHOCYTES-T; DNA CLEAVAGE; ANTIGEN; CYTOTOXICITY; ACTIVATION; INHIBITOR; PHARMACOLOGY AB Accumulation of extracellular and intracellular adenosine (Ado) under hypoxic conditions or in the absence of adenosine deaminase results in lymphocyte depletion and in severe combined immunodeficiency, which are currently explained by direct intracellular lymphotoxicity of Ado metabolites. In support of the alternative, ''signaling'' mechanism, we show that extracellular Ado (extAdo) suppresses all tested T cell receptor (TCR)triggered effector functions of T Lymphocytes including the TCR-triggered Fast mRNA up-regulation in cytotoxic T lymphocytes. Strong evidence against the intracellular lymphotoxicity of Ado (and in support of the signaling model) is provided by abrogation of TCR-triggered growth inhibition in Ado exposed T cells. The brief exposure to Ado was sufficient to observe inhibition of TCR-triggered effector functions. The ''memory'' of T cells to exposure to extAdo is best explained by sustained increases in cAMP. Selective agonist (CGS21680) and antagonist (ZM241385) of A(2A) adenosine receptor were used in functional assays and cDNA probes for different sybtypes of adenosine receptors were used in Northern blot studies. A(2A) receptors are identified as the predominantly expressed subtype of G(s)-coupled Ado receptors in T cells, The demonstration of cross-talk between the A(2A) receptors and TCR in both directions support the possible role of A(2A) receptors in mechanisms of extAdo-mediated immunosuppression in vivo under adenosine deaminase deficiency and hypoxic conditions in, e.g., solid tumors. C1 NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NR 41 TC 122 Z9 124 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 10 PY 1997 VL 272 IS 41 BP 25881 EP 25889 DI 10.1074/jbc.272.41.25881 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YA358 UT WOS:A1997YA35800075 PM 9325320 ER PT J AU Davis, DA Newcomb, FM Starke, DW Ott, DE Mieyal, JJ Yarchoan, R AF Davis, DA Newcomb, FM Starke, DW Ott, DE Mieyal, JJ Yarchoan, R TI Thioltransferase (glutaredoxin) is detected-within HIV-1 and can regulate the activity of glutathionylated HIV-1 protease in vitro SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; OXIDATIVE STRESS; S-THIOLATION; ESCHERICHIA-COLI; VIRAL INFECTIVITY; CYSTEINE RESIDUES; RESPIRATORY BURST; VACCINIA VIRUS; TYPE-1; PROTEINS AB Previous studies have suggested that the two conserved cysteines of the HIV-1 protease may be involved in regulating protease activity, Here, we examined diglutathionylated wild type protease (Cys-67-SSG, Cys-95-SSG) and the monoglutathionylated protease mutants (C67A, Cys-95-SSG and C95A, Cys-67-SSG) as potential substrates for thioltransferase (glutaredoxin). Time-dependent changes in the extent of deglutathionylation of each protein were assayed by reverse phase-high performance liquid chromatography. Glutathione alone was not an effective reductant, whereas thioltransferase displayed differential catalysis toward the Cys-95-SSG and Cys-67-SSG sites. At low thioltransferase concentrations (5 nM), deglutathionylation occurred almost exclusively at Cys-95-SSG. With substantially more thioltransferase (100 nM) Cys-67-SSG was partially deglutathionylated but only at 20% of the rate of Cys-95-SSG reduction, Treatment of the diglutathionylated protease with thioltransferase not only restored protease activity but generated an enzyme preparation that had a 3- to 5-fold greater specific activity relative to the fully reduced form, Immunoblot analysis of HIV-1(MN) virus with an antibody to thioltransferase detected a band co-migrating with recombinant thioltransferase that persisted following subtilisin treatment, indicating the presence of thioltransferase within HIV-1. Our results implicate thioltransferase in the regulation and/or maintenance of protease activity in HIV-1 infected cells. C1 CASE WESTERN RESERVE UNIV,SCH MED,DEPT PHARMACOL,CLEVELAND,OH 44106. SCI APPLICAT INT CORP,AIDS VACCINE PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. RP Davis, DA (reprint author), NCI,HIV & AIDS MALIGNANCY BRANCH,NIH,BETHESDA,MD 20892, USA. NR 55 TC 114 Z9 117 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 10 PY 1997 VL 272 IS 41 BP 25935 EP 25940 DI 10.1074/jbc.272.41.25935 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YA358 UT WOS:A1997YA35800082 PM 9325327 ER PT J AU Mantey, SA Weber, HC Sainz, E Akeson, M Ryan, RR Pradhan, TK Searles, RP Spindel, ER Battey, JF Coy, DH Jensen, RT AF Mantey, SA Weber, HC Sainz, E Akeson, M Ryan, RR Pradhan, TK Searles, RP Spindel, ER Battey, JF Coy, DH Jensen, RT TI Discovery of a high affinity radioligand for the human orphan receptor, bombesin receptor subtype 3, which demonstrates that it has a unique pharmacology compared with other mammalian bombesin receptors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GASTRIN-RELEASING PEPTIDE; SWISS 3T3 CELLS; PANCREATIC ACINAR-CELLS; LUNG-CARCINOMA CELLS; ANTAGONIST ACTIVITY; ANTIMITOTIC ACTIVITY; LIGAND-BINDING; POTENT; ANALOGS; INTERNALIZATION AB An orphan receptor discovered in 1993 was called bombesin receptor subtype 3 (BRS-3) because of 47-51% amino acid identity with bombesin (Bn) receptors. Its pharmacology is unknown, because no naturally occurring tissues have sufficient receptors to allow studies. We made two cell lines stably expressing the human BRS-3 (hBRS-3). hBRS-3 was overexpressed in the human non-small cell lung cancer cells, NCI-H1299, and the other was made in Balb 3T3 cells, which lack endogenous BRS-3. [D-Phe(6),beta-Ala(11),Phe(13),Nle(14)]Bn-(6-14) (where Nle represents norleucine) was discovered to have high potency for stimulating inositol phosphate formation in both cell lines. [I-125-D-Tyr(6),beta-Ala(11),Phe(13),Nle(14)]Bn-(6-14) bound to both cell lines with high affinity. Neither Bn nor 14 other naturally occurring Bn peptides bound to hBRS-3 with a K-d <1000 nM. Twenty-six synthetic peptides that are high affinity agonists or antagonists at other bombesin receptors had an affinity >1000 nM. Guanosine 5'-(beta,gamma-imido)triphosphate inhibited binding to both cells due to a change in receptor affinity. These results demonstrate hBRS-3 has a unique pharmacology. It does not interact with high affinity with any known natural agonist or high affinity antagonist of the Bn receptor family, suggesting the natural ligand is either an undiscovered member of the Bn peptide family or an unrelated peptide. The availability of these cell lines and the hBRS-3 ligand should facilitate identification of the natural ligand for BRS-3, its pharmacology, and cell biology. C1 NIDDK,NIH,DDB,BETHESDA,MD 20892. NIDOCD,NIH,ROCKVILLE,MD 20850. TULANE UNIV,PEPTIDE RES LABS,NEW ORLEANS,LA 70117. OREGON REG PRIMATE RES CTR,DIV NEUROSCI,BEAVERTON,OR 97006. NR 41 TC 130 Z9 133 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 10 PY 1997 VL 272 IS 41 BP 26062 EP 26071 DI 10.1074/jbc.272.41.26062 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YA358 UT WOS:A1997YA35800099 PM 9325344 ER PT J AU BanikMaiti, S King, RA Weisberg, RA AF BanikMaiti, S King, RA Weisberg, RA TI The antiterminator RNA of phage HK022 SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE transcriptional regulatory elements; regulatory RNA; bacteriophage HK022; RNA polymerase; transcription termination ID SITE-DIRECTED MUTAGENESIS; EARLY TRANSCRIPTION; POLYMERASE; RECOGNITION; REGION AB The put sites of phage HK022 increase the processivity of transcription and thereby promote the expression of viral genes that are located downstream of transcription terminators. RNA polymerase molecules that have traversed a put site are converted to a terminator-resistant form by the put transcript. We analyzed the structure and function of put transcripts by determining the effects of put mutations on terminator read-through, and by probing wild-type and mutant put RNAs with structure-specific nucleases. The results support the prediction that the secondary structure of the active transcript consists of two hairpin stems that are separated by a single unpaired base. The identity of bases in certain bulges and internal loops is important for activity, while that of most bases in the terminal loops is not. Many bases in the stems can be replaced with little or no effect on activity provided that base-pairing is maintained. (C) 1997 Academic Press Limited. C1 NICHHD, SECT MICROBIAL GENET, GENET MOL LAB, NIH, BETHESDA, MD 20892 USA. NR 15 TC 17 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD OCT 10 PY 1997 VL 272 IS 5 BP 677 EP 687 DI 10.1006/jmbi.1997.1251 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YB267 UT WOS:A1997YB26700003 PM 9368650 ER PT J AU Iadarola, MJ Caudle, RM AF Iadarola, MJ Caudle, RM TI Neuroscience - Good pain, bad pain SO SCIENCE LA English DT Editorial Material ID RECEPTOR MESSENGER-RNA; RAT SPINAL-CORD; EXPRESSION; INFLAMMATION; CELLS RP Iadarola, MJ (reprint author), NIDR,PAIN & NEUROSENSORY MECH BRANCH,BETHESDA,MD 20892, USA. NR 16 TC 20 Z9 20 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 10 PY 1997 VL 278 IS 5336 BP 239 EP 240 DI 10.1126/science.278.5336.239 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YA564 UT WOS:A1997YA56400030 ER PT J AU Takahashi, N De Luca, LM Breitman, TR AF Takahashi, N De Luca, LM Breitman, TR TI Decreased retinoylation in NIH 3T3 cells transformed with activated Ha-ras SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID RETINOIC ACID RECEPTOR; PROTEINS; EXPRESSION; LINES; IDENTIFICATION; FIBRONECTIN; METABOLISM; INHIBITION; ONCOGENES; CARCINOMA AB Retinoylation (retinoic acid acylation) is a post-translation modification of proteins occurring in a variety of mammalian cell lines and in vivo, To gain further knowledge of the role of retinoylation we studied it in NIH 3T3 cells and NIH 3T3 cells transformed by an activated Ha-ras oncogene (NIH Ha-ras-3T3 cells), In serum-free medium retinoic acid (RA) inhibited growth of NIH 3T3 cells but did not inhibit growth of NIH Ha-ras-3T3 cells, After incubation with [H-3]RA, the level of retinoylated protein in NIH 3T3 cells was about 1.5-fold greater than in NIH Ha-ras-3T3 cells, On one-dimensional polyacrylamide gel electrophoresis, both the rate and the extent of retinoylation were greater in NIH 3T3 cells, We detected about 40 retinoylated proteins in NIH 3T3 cells by two-dimensional polyacrylamide gel electrophoresis. Only about 15 proteins were retinoylated, but at reduced levels, in NIH Ha-ras-3T3 cells, These results suggest that the activated ras oncogene inhibits retinoylation. This inhibition may in turn be related to the loss of other RA responses of NIH 3T3 cells, including growth inhibition, retinoic acid catabolism, down-regulation of fibronectin biosynthesis, and induction of tissue-type transglutaminase, which are not seen to the same extent in NIH Ha-ras-3T3 cells. (C) 1997 Academic Press. C1 NCI, BIOL CHEM LAB, DIV BASIC SCI, NIH, BETHESDA, MD 20892 USA. RP Takahashi, N (reprint author), HOSHI UNIV, DEPT HLTH CHEM, SINAGAWA KU, 4-41 EBARA 2 CHOME, TOKYO 142, JAPAN. NR 34 TC 5 Z9 6 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 9 PY 1997 VL 239 IS 1 BP 80 EP 84 DI 10.1006/bbrc.1997.7434 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YB131 UT WOS:A1997YB13100015 PM 9345273 ER PT J AU Pili, R Chang, J Muhlhauser, J Crystal, RG Capogrossi, MC Passaniti, A AF Pili, R Chang, J Muhlhauser, J Crystal, RG Capogrossi, MC Passaniti, A TI Adenovirus-mediated gene transfer of fibroblast growth factor-1: Angiogenesis and tumorigenicity in nude mice SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID TUMOR-GROWTH; REPLICATION-DEFICIENT; NONSECRETED FORMS; ATHYMIC MICE; FACTOR-I; CARCINOMA; INVIVO; VECTORS; CELLS; NEOVASCULARIZATION AB Gene transfer of angiogenic growth factors with replication-deficient recombinant adenovirus (Ad) vectors may provide a new approach to the treatment of ischemic diseases. To determine if Ad-infected cells could stimulate angiogenesis in vivo and to assess the tumorigenicity of cells infected with these vectors, NIH3T3 fibroblasts infected with Ad vectors coding for human acidic fibroblast growth factor (aFGF-I) were used in angiogenic and tumorigenic assays. Infected cells induced a strong angiogenic response in vivo, while cells infected with control virus did not, Stable 3T3 transfectants expressing the FCF-I gene were also highly angiogenic and exhibited growth in soft agar, while Ad-infected cells did not, Ad-infected cells grew transiently in nude mice, whereas 3T3 transfectants formed large tumors which grew exponentially, Extrapolation of cell dose-response curves showed that a minimum of 1.5 x 10(4) infected cells were required for transient tumor cell growth in vivo, Ad-infected cells cultured in vitro for 30 days lost their invasive phenotype and the ability for transient cell growth in nude mice. Thus, phenotypic changes induced by Ad-mediated gene transfer of FGF-I are transient both in vitro and in vivo, suggesting that these Ad vectors do not have tumorigenic potential, Stimulation of angiogenesis by Ad-infected cells may be useful for the evaluation of anti-angiogenic and anti-tumor agents. (C) 1997 Wiley-Liss, Inc. C1 NIH,CELL BIOL UNIT,BIOL CHEM LAB,BALTIMORE,MD. NIA,GENE THERAPY UNIT,CARDIOVASC SCI LAB,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. NEW YORK HOSP,CORNELL MED CTR,DIV PULM & CRIT CARE MED,NEW YORK,NY 10021. IST DERMOPAT IMMACOLATA,LAB PATOL VASC,ROME,ITALY. NR 25 TC 3 Z9 6 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD OCT 9 PY 1997 VL 73 IS 2 BP 258 EP 263 PG 6 WC Oncology SC Oncology GA XZ488 UT WOS:A1997XZ48800016 PM 9335452 ER PT J AU DeLuca, A Selvam, MP Sandomenico, C Pepe, S Bianco, AR Ciardiello, F Salomon, DS Normanno, N AF DeLuca, A Selvam, MP Sandomenico, C Pepe, S Bianco, AR Ciardiello, F Salomon, DS Normanno, N TI Anti-sense oligonucleotides directed against EGF-related growth factors enhance anti-proliferative effect of conventional anti-tumor drugs in human colon-cancer cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID RECEPTOR MONOCLONAL-ANTIBODIES; FACTOR-RELATED PEPTIDES; CARCINOMA CELLS; HUMAN MALIGNANCIES; COLORECTAL TUMORS; TYROSINE KINASE; HUMAN BREAST; FACTOR-ALPHA; DNA-REPAIR; EXPRESSION AB We have demonstrated that anti-sense phosphorothioate oligodeoxynucleotides (AS S-oligos) directed against the EGF-like growth factors CRIFTO (CR), amphiregulin (AR) or transforming-growth-factor-alpha(TGF alpha) mRNA, are equipotent in their ability to inhibit the growth of human colon-carcinoma GEO cells. In this study, we evaluated the effect of combinations of these AS S-oligos and conventional antitumor drugs, such as 5-fluorouracil (5-FU), adriamycin (ADR), mitomycin C (MlT) and cis-platinum (CDDP), on GEO cell growth. Dose-dependent growth inhibition was observed by treatment either with AS S-oligos or with anti-tumor drugs, using a clonogenic assay. Furthermore, an additive growth-inhibitory effect occurred when GEO cells were exposed to the AS S-oligos after treatment with different concentrations of either 5-FU, MIT, ADR or CDDP. For example, treatment of GEO cells with a combination of low concentrations of 5-FU and any of the 3 AS S-oligos resulted in up to 70% growth inhibition. However, treatment of GEO cells with AS S-oligos before exposure to 5-FU or CDDP resulted in reduced efficacy of both drugs. Flow-cytometric analysis of DNA content demonstrated that treatment with the AS S-oligos caused a slight reduction of the percentage of cells in the S-phase of the cell cycle. These data suggest that combinations of AS S-oligos directed against EGF-related growth factors and of conventional anti-tumor drugs may result in efficient inhibition of colon-carcinoma cell growth. (C) 1997 Wiley-Liss, Inc. C1 ITN FDN PASCALE,ONCOL SPERIMENTALE D,I-80131 NAPLES,ITALY. US FDA,DBA CBER,ROCKVILLE,MD 20852. UNIV NAPLES FEDERICO II,FAC MED & CHIRURG,DIPARTIMENTO ENDOCRINOL & ONCOL MOL & CLIN,I-80131 NAPLES,ITALY. NCI,TUMOR GROWTH FACTOR SECT,LTIB,NIH,BETHESDA,MD 20892. RI De Luca, Antonella/J-8737-2016; OI De Luca, Antonella/0000-0001-5762-447X; Ciardiello, Fortunato/0000-0002-3369-4841; Normanno, Nicola/0000-0002-7158-2605 NR 25 TC 35 Z9 35 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD OCT 9 PY 1997 VL 73 IS 2 BP 277 EP 282 DI 10.1002/(SICI)1097-0215(19971009)73:2<277::AID-IJC19>3.0.CO;2-C PG 6 WC Oncology SC Oncology GA XZ488 UT WOS:A1997XZ48800019 PM 9335455 ER PT J AU Fukada, K Gershfeld, NL AF Fukada, K Gershfeld, NL TI Influence of hydration on the formation and stability of the critical bilayer state SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID PHOSPHOLIPID SURFACE BILAYERS; AIR-WATER-INTERFACE; TEMPERATURE AB Phospholipid dispersions that undergo a multilamellar vesicle (MLV) to unilamellar vesicle (ULV) transformation at a critical temperature T* form a single bilayer spontaneously and rapidly at the air-water interface. The ''surface bilayer'' rapidly covers the entire air-water surface, yielding a surface tension similar to 70 mN/m. This indicates that the outermost layer of the surface bilayer is its hydration layer. At 100% relative humidity (R.H.) the surface bilayer is stable indefinitely but becomes unstable, forming a monolayer, when the R.H. is reduced. The rate of breakdown to monolayer varies inversely with the R.H. The rapid formation of the surface bilayer is a manifestation of the superposition of surface forces on the MLV-ULV transformation that occurs simultaneously within the bulk dispersion at T*. Surface forces act primarily to accelerate the MLV-ULV transformation. C1 NIAMSD, NIH, BETHESDA, MD 20892 USA. NR 24 TC 1 Z9 1 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD OCT 9 PY 1997 VL 101 IS 41 BP 8225 EP 8230 DI 10.1021/jp970928m PG 6 WC Chemistry, Physical SC Chemistry GA YA485 UT WOS:A1997YA48500027 ER PT J AU Mayer, M AF Mayer, M TI Kainate receptors - Finding homes at synapses SO NATURE LA English DT Editorial Material ID HIPPOCAMPAL-NEURONS; GLUTAMATE-RECEPTOR; ANTAGONISM RP Mayer, M (reprint author), NICHHD,LAB CELLULAR & MOL NEUROPHYSIOL,NIH,BETHESDA,MD 20892, USA. RI Mayer, Mark/H-5500-2013 NR 12 TC 12 Z9 12 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD OCT 9 PY 1997 VL 389 IS 6651 BP 542 EP 543 DI 10.1038/39177 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YA008 UT WOS:A1997YA00800027 PM 9335486 ER PT J AU Levine, RJ AF Levine, RJ TI Contempo 1997: Obstetrics and gynecology SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID HYPERTENSION RP Levine, RJ (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 5 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 OCT 8 PY 1997 VL 278 IS 14 BP 1147 EP 1147 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA XY422 UT WOS:A1997XY42200017 PM 9326465 ER PT J AU Lebowitz, BD Pearson, JL Schneider, LS Reynolds, CF Alexopoulos, GS Bruce, ML Conwell, Y Katz, IR Meyers, BS Morrison, MF Mossey, J Niederehe, G Parmelee, P AF Lebowitz, BD Pearson, JL Schneider, LS Reynolds, CF Alexopoulos, GS Bruce, ML Conwell, Y Katz, IR Meyers, BS Morrison, MF Mossey, J Niederehe, G Parmelee, P TI Diagnosis and treatment of depression in late life - Consensus statement update SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PRIMARY-CARE PATIENTS; MAJOR DEPRESSION; GENERAL-PRACTITIONERS; GERIATRIC DEPRESSION; PHYSICAL HEALTH; FOLLOW-UP; SUICIDE; SYMPTOMS; MOOD; ANTIDEPRESSANTS AB Objective.-To reexamine the conclusions of the 1991 National Institutes of Health Consensus Panel on Diagnosis and Treatment of Depression in Late Life in light of current scientific evidence. Participants.-Participants included National institutes of Health staff and experts drawn from the Planning Committee and presenters of the 1991 Consensus Development Conference. Evidence.-Participants summarized relevant data from the world scientific literature on the original questions posed for the conference. Process.-Participants reviewed the original consensus statement and identified areas for update. The list of issues was circulated to all participants and amended to reflect group agreement. Selected participants prepared first drafts of the consensus update for each issue. All drafts were read by all participants and were amended and edited to reflect group consensus. Conclusions.-The review concluded that, although the initial consensus statement still holds, there is important new information in a number of areas. These areas include the onset and course of late-life depression; comorbidity and disability; sex and hormonal issues; newer medications, psychotherapies, and approaches to long-term treatment; impact of depression on health services and health care resource use; late-life depression as a risk factor for suicide; and the importance of the heterogeneous forms of depression, Depression in older people remains a significant public health problem. The burden of unrecognized or inadequately treated depression is substantial, Efficacious treatments are available. Aggressive approaches to recognition, diagnosis, and treatment are warranted to minimize suffering, improve overall functioning and quality of life, and limit inappropriate use of health care resources. C1 UNIV SO CALIF, LOS ANGELES, CA 90089 USA. UNIV PITTSBURGH, PITTSBURGH, PA 15260 USA. CORNELL UNIV, MED CTR, WHITE PLAINS, NY 10605 USA. UNIV ROCHESTER, ROCHESTER, NY 14627 USA. UNIV PENN, PHILADELPHIA, PA 19104 USA. ALLEGHENY UNIV HLTH SCI, PHILADELPHIA, PA 19102 USA. RP Lebowitz, BD (reprint author), NIMH, 5600 FISHERS LN, ROOM 18-101, ROCKVILLE, MD 20857 USA. NR 63 TC 471 Z9 484 U1 4 U2 20 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 8 PY 1997 VL 278 IS 14 BP 1186 EP 1190 DI 10.1001/jama.278.14.1186 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA XY422 UT WOS:A1997XY42200039 PM 9326481 ER PT J AU Ronne, C Thrane, L Astrand, PO Wallqvist, A Mikkelsen, KV Keiding, SR AF Ronne, C Thrane, L Astrand, PO Wallqvist, A Mikkelsen, KV Keiding, SR TI Investigation of the temperature dependence of dielectric relaxation in liquid water by THz reflection spectroscopy and molecular dynamics simulation SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID EFFECTIVE PAIR POTENTIALS; TIME-DOMAIN SPECTROSCOPY; COMPUTER-SIMULATIONS; OPTICAL-CONSTANTS; COMPLEX PERMITTIVITY; SOLVATION DYNAMICS; SUPERCOOLED WATER; CHARGE; MODEL; H2O AB We report measurements of the real and imaginary part of the dielectric constant of liquid water in the far-infrared region from 0.1 to 2.0 THz in a temperature range from 271.1 to 366.7 K. The data have been obtained with the use of THz time domain reflection spectroscopy, utilizing ultrashort electromagnetic pulses generated from a photoconductive antenna driven by femtosecond laser pulses. A Debye model with an additional relaxation time is used to fit the frequency dependence of the complex dielectric constants, We obtain a fast (fs) and a Debye (ps) relaxation time for the macroscopic polarization. The corresponding time correlation functions have been calculated with molecular dynamics simulations and are compared with experimental relaxation times. The temperature dependence of the Debye relaxation time is analyzed using three models: Transition state theory, a Debye-Stoke-Einstein relation between the viscosity and the Debye time, and a model stating that its temperature dependence can be extrapolated from a singularity of liquid water at 228 K. We find an excellent agreement between experiment and the two latter models. The simulations, however, present results with too large statistical error for establishing a relation for the temperature dependence. (C) 1997 American Institute of Physics. C1 UNIV COPENHAGEN, HC ORSTED INST, CHEM LAB 3, DK-2100 COPENHAGEN O, DENMARK. NCI, FREDERICK CANC RES & DEV CTR, SCI APPLICAT INT CORP, FREDERICK, MD 21702 USA. RP AARHUS UNIV, DEPT CHEM, LANGELANDSGADE 140, DK-8000 AARHUS C, DENMARK. RI Astrand, Per-Olof/H-6879-2012; Mikkelsen, K./E-6765-2015; Keiding, Soren/B-6728-2008; OI Astrand, Per-Olof/0000-0003-3384-7585; Mikkelsen, K./0000-0003-4090-7697; Keiding, Soren/0000-0003-1608-9639; wallqvist, anders/0000-0002-9775-7469 NR 87 TC 355 Z9 357 U1 9 U2 104 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 0021-9606 EI 1089-7690 J9 J CHEM PHYS JI J. Chem. Phys. PD OCT 8 PY 1997 VL 107 IS 14 BP 5319 EP 5331 PG 13 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA XZ871 UT WOS:A1997XZ87100005 ER PT J AU Tjandra, N Bax, A AF Tjandra, N Bax, A TI Large variations in C-13(alpha) chemical shift anisotropy in proteins correlate with secondary structure SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID SOLID-STATE; C-13 NMR; CONFORMATION; RELAXATION; RESOLUTION; UBIQUITIN; DYNAMICS C1 NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. NIDDKD,BIOPHYS CHEM LAB,NIH,BETHESDA,MD 20892. NR 20 TC 121 Z9 122 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD OCT 8 PY 1997 VL 119 IS 40 BP 9576 EP 9577 DI 10.1021/ja9721374 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA YA232 UT WOS:A1997YA23200037 ER PT J AU Chaitman, BR Rosen, AD Williams, DO Bourassa, MG Aguirre, FV Pitt, B Rautaharju, PM Rogers, WJ Sharaf, B Attubato, M Hardison, RM Srivatsa, S Kouchoukos, NT Stocke, K Sopko, G Detre, K Frye, R AF Chaitman, BR Rosen, AD Williams, DO Bourassa, MG Aguirre, FV Pitt, B Rautaharju, PM Rogers, WJ Sharaf, B Attubato, M Hardison, RM Srivatsa, S Kouchoukos, NT Stocke, K Sopko, G Detre, K Frye, R TI Myocardial infarction and cardiac mortality in the bypass angioplasty revascularization investigation (BARI) randomized trial SO CIRCULATION LA English DT Article DE bypass; angioplasty; mortality; myocardial infarction; prognosis ID COMPARING CORONARY ANGIOPLASTY; SURGERY; RECRUITMENT; PROGNOSIS; NOVACODE; DISEASE; RISK AB Background Cardiac mortality and myocardial infarction (MI) rates are used to evaluate the efficacy of coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA). We compared 5-year cardiac mortality and MI rates in 1829 patients with multivessel disease randomized to CABG or PTCA. Methods and Results The 5-year cardiac mortality rate was 8.0% in patients assigned to PTCA compared with 4.9% in those assigned to CABG (relative risk [RR] of 1.55 with a 95% confidence interval [CI] of 1.07 to 2.23; P = .022). In a subgroup of 1476 nondiabetic patients, there were no significant differences between treatment groups in cardiac mortality either overall (4.6% versus 4.2%; RR = 1.04, 95% CI, 0.65 to 1.66; P = .908) or in subgroups based on symptoms, left ventricular function, number of diseased vessels, or stenotic proximal left anterior descending artery. The two treatment groups had similar event rates for the combined end point of cardiac death or MI. The RR for cardiac mortality in 264 patients who sustained an MI compared with those who did not was 5.9 (P < .001). Mrs were more common after CABG during index hospitalization (P = .004), but in the PTCA group, they were more common after discharge (P < .001). Conclusions The Bypass Angioplasty Revascularization Investigation (BARI) trial indicates 5-year cardiac mortality in patients with multivessel disease was significantly greater after initial treatment with PTCA than with CABG. The difference was manifest in diabetic patients on drug therapy. There were no significant differences overall for the composite end point of cardiac mortality or MI between treatment groups or for cardiac mortality in nondiabetic patients regardless of symptoms, left ventricular function, number of diseased vessels, or stenotic proximal left anterior descending artery. C1 UNIV PITTSBURGH,PITTSBURGH,PA 15260. BROWN UNIV,PROVIDENCE,RI 02912. MONTREAL HEART INST,MONTREAL,PQ H1T 1C8,CANADA. UNIV MICHIGAN,ANN ARBOR,MI 48109. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. UNIV ALABAMA,BIRMINGHAM,AL. NYU,NEW YORK,NY. MAYO CLIN,ROCHESTER,MN. WASHINGTON UNIV,ST LOUIS,MO 63130. NHLBI,BETHESDA,MD 20892. RP Chaitman, BR (reprint author), ST LOUIS UNIV,HLTH SCI CTR,DIV CARDIOL,SCH MED,13TH FLOOR,3635 VISTA AVE & GRAND BLVD,POB 15250,ST LOUIS,MO 63110, USA. RI srivatsa, sanjay/C-6359-2011; OI Bourassa, Martial G./0000-0002-4439-8650 FU NHLBI NIH HHS [HL-38504, HL-38493, HL-38509] NR 33 TC 73 Z9 74 U1 1 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 7 PY 1997 VL 96 IS 7 BP 2162 EP 2170 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YA098 UT WOS:A1997YA09800011 PM 9337185 ER PT J AU Psaty, BM Manolio, TA Kuller, LH Kronmal, RA Cushman, M Fried, LP White, R Furberg, CD Rautaharju, PM AF Psaty, BM Manolio, TA Kuller, LH Kronmal, RA Cushman, M Fried, LP White, R Furberg, CD Rautaharju, PM TI Incidence of and risk factors for atrial fibrillation in older adults SO CIRCULATION LA English DT Article DE fibrillation; atrial flutter; epidemiology; follow-up studies; risk factors ID CARDIOVASCULAR HEALTH; HEART-DISEASE; DRUG-THERAPY; STROKE; POPULATION; PREVALENCE; FEATURES AB Background This study aimed to describe the incidence of atrial fibrillation (AF) among older adults during 3 years of follow-up. Methods and Results In this cohort study, 5201 adults greater than or equal to 65 years old were examined annually on four occasions between June 1989 and May 1993. Ar baseline, participants answered questionnaires and underwent a detailed examination that included carotid ultrasound, pulmonary function tests, EGG, and echocardiography. Subjects with a pacemaker or AF at baseline (n = 357) were excluded. New cases of AF were identified from three sources: (1) annual self-reports, (2) annual ECGs, and (3) hospital discharge diagnoses. Cox proportional-hazards models were used to assess baseline risk factors as predictors of incident AF. Among 4844 participants, 304 developed a first episode of AF during an average follow-up of 3.28 years, for an incidence of 19.2 per 1000 person-years. The onset was strongly associated with age, male sex, and the presence of clinical cardiovascular disease. For men 65 to 74 and 75 to 84 years old, the incidences were 17.6 and 42.7, respectively, and for women, 10.1 and 21.6 events per 1000 person-years. In stepwise models, the use of diuretics, a history of valvular heart disease, coronary disease, advancing age, higher levels of systolic blood pressure, height, glucose, and left atrial size were all associated with an increased risk of AF. The use of beta-blockers and high levels of alcohol use, cholesterol, and forced expiratory volume in 1 second were associated with a reduced risk of AF. Conclusions The incidence of AF in older adults may be higher than estimated by previous population studies. Left atrial size appears to be an important risk factor, and the control of blood pressure and glucose may be important in preventing the development of AF. C1 UNIV WASHINGTON,DEPT MED,CARDIOVASC HLTH RES UNIT,SEATTLE,WA. UNIV WASHINGTON,DEPT EPIDEMIOL,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT HLTH SERV,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT BIOSTAT,SEATTLE,WA 98195. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT EPIDEMIOL,PITTSBURGH,PA 15260. UNIV VERMONT,DEPT MED,BURLINGTON,VT. JOHNS HOPKINS UNIV,DEPT MED,BALTIMORE,MD. JOHNS HOPKINS UNIV,DEPT EPIDEMIOL,BALTIMORE,MD. UNIV CALIF DAVIS,DEPT MED,DAVIS,CA. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. FU NHLBI NIH HHS [N01-HC-85080, N01-HC-85079, N01-HC-85081] NR 37 TC 780 Z9 805 U1 6 U2 17 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 7 PY 1997 VL 96 IS 7 BP 2455 EP 2461 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YA098 UT WOS:A1997YA09800050 PM 9337224 ER PT J AU Radhakrishna, H Donaldson, JG AF Radhakrishna, H Donaldson, JG TI ADP-ribosylation factor 6 regulates a novel plasma membrane recycling pathway SO JOURNAL OF CELL BIOLOGY LA English DT Article ID GTP-BINDING-PROTEIN; RECEPTOR-MEDIATED ENDOCYTOSIS; MHC CLASS-II; BREFELDIN-A; GOLGI MEMBRANES; PHOSPHOLIPASE-D; ORGANELLE STRUCTURE; GUANINE-NUCLEOTIDE; MAMMALIAN-CELLS; COATED VESICLES AB ADP-ribosylation factor (ARF) 6 localizes to the plasma membrane (PM) in its GTP state and to a tubulovesicular compartment in its GDP state in HeLa cells that express wild-type or mutant forms of this GTPase. Aluminum fluoride (AlF) treatment of ARF6-transfected cells redistributes ARF6 to the PM and stimulates the formation of actin-rich surface protrusions. Here we show that cytochalasin D (CD) treatment inhibited formation of the AlF-induced protrusions and shifted the distribution of ARF6 to a tubular membrane compartment emanating from the juxtanuclear region of cells, which resembled the compartment where the GTP-binding defective mutant of ARF6 localized. This membrane compartment was distinct from transferrin-positive endosomes, could be detected in the absence of ARF6 overexpression or CD treatment, and was accessible to loading by PM proteins lacking clathrin/AP-2 cytoplasmic targeting sequences, such as the IL-2 receptor alpha subunit Tac. ARF6 and surface Tac moved into this compartment and back out to the PM in the absence of pharmacologic treatment. Whereas AlF treatment blocked internalization, CD treatment blocked the recycling of wild-type ARF6 and Tac back to the PM; these blocks were mimicked by expression of ARF6 mutants Q67L and T27N, which were predicted to be in either the GTP- or GDP-bound state, respectively. Thus, the ARF6 GTP cycle regulates this membrane traffic pathway. The delivery of ARF6 and membrane to defined sites along the PM may provide components necessary for remodeling the cell surface and the underlying actin cytoskeleton. C1 NHLBI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NR 63 TC 357 Z9 358 U1 5 U2 9 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD OCT 6 PY 1997 VL 139 IS 1 BP 49 EP 61 DI 10.1083/jcb.139.1.49 PG 13 WC Cell Biology SC Cell Biology GA YB446 UT WOS:A1997YB44600005 PM 9314528 ER PT J AU Terasaki, M Miyake, K McNeil, PL AF Terasaki, M Miyake, K McNeil, PL TI Large plasma membrane disruptions are rapidly resealed by Ca2+-dependent vesicle-vesicle fusion events SO JOURNAL OF CELL BIOLOGY LA English DT Article ID SQUID GIANT-AXON; SEA-URCHIN EGGS; ENDOPLASMIC-RETICULUM; CORTICAL GRANULES; CALCIUM-IONS; PROTEIN; FERTILIZATION; OOCYTES; CELLS; ACCUMULATION AB A microneedle puncture of the fibroblast or sea urchin egg surface rapidly evokes a localized exocytotic reaction that may be required for the rapid resealing that follow this breach in plasma membrane integrity (Steinhardt, R.A,. G. Bi, and J.M. Alderton. 1994. Science (Wash. DC). 263:390-393). How this exocytotic reaction facilitates the resealing process is unknown. We found that starfish oocytes and sea urchin eggs rapidly reseal much larger disruptions than those produced with a microneedle. When an similar to 40 by 10 mu m surface patch was torn off, entry of fluorescein stachyose (FS; 1,000 mol wt) or fluorescein dextran (FDx; 10,000 mol wt) from extracellular sea water (SW) was not detected by confocal microscopy. Moreover, only a brief (similar to 5-10 s) rise in cytosolic Ca2+ was detected at the wound site. Several lines of evidence indicate that intracellular membranes are the primary source of the membrane recruited for this massive resealing event. When we injected FS-containing SW deep into the cells, a vesicle formed immediately, entrapping within its confines most of the FS. DiI staining and EM confirmed that the barrier delimiting injected SW was a membrane bilayer. The threshold for vesicle formation was similar to 3 mM Ca2+ (SW is similar to 10 mM Ca2+). The capacity of intracellular membranes for sealing off SW was further demonstrated by extruding egg cytoplasm from a micropipet into SW. A boundary immediately formed around such cytoplasm, entrapping FDx or FS dissolved in it. This entrapment did not occur in Ca2+-free SW (CFSW). When egg cytoplasm stratified by centrifugation was exposed to SW, only the yolk platelet-rich domain formed a membrane, suggesting that the yolk platelet is a critical element in this response and that the ER is not required. We propose that plasma membrane disruption evokes Ca2+ regulated vesicle-vesicle (including endocytic compartments but possibly excluding ER) fusion reactions. The function in resealing of this cytoplasmic fusion reaction is to form a replacement bilayer patch. This patch is added to the discontinuous surface bilayer by exocytotic fusion events. C1 MARINE BIOL LAB, WOODS HOLE, MA 02543 USA. NINCDS, NEUROBIOL LAB, NIH, BETHESDA, MD 20892 USA. FUKUSHIMA MED COLL, DEPT ANAT 2, FUKUSHIMA 96012, JAPAN. MED COLL GEORGIA, DEPT CELLULAR BIOL & ANAT, AUGUSTA, GA 30912 USA. RP UNIV CONNECTICUT, CTR HLTH, DEPT PHYSIOL, FARMINGTON, CT 06032 USA. FU PHS HHS [48091] NR 57 TC 164 Z9 166 U1 3 U2 12 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD OCT 6 PY 1997 VL 139 IS 1 BP 63 EP 74 DI 10.1083/jcb.139.1.63 PG 12 WC Cell Biology SC Cell Biology GA YB446 UT WOS:A1997YB44600006 PM 9314529 ER PT J AU Sugiyama, JE Glass, DJ Yancopoulos, GD Hall, ZW AF Sugiyama, JE Glass, DJ Yancopoulos, GD Hall, ZW TI Laminin-induced acetylcholine receptor clustering: An alternative pathway SO JOURNAL OF CELL BIOLOGY LA English DT Article ID DYSTROPHIN-ASSOCIATED GLYCOPROTEIN; CULTURED MUSCLE-CELLS; TYROSINE KINASE MUSK; NEUROMUSCULAR-JUNCTION; EXTRACELLULAR-MATRIX; BASEMENT-MEMBRANES; SKELETAL-MUSCLE; AGRIN RECEPTOR; SYNAPTIC CLEFT; HIGH-AFFINITY AB The induction of acetylcholine receptor (AChR) clustering by neurally released agrin is a critical, early step in the formation of the neuromuscular junction. Laminin, a component of the muscle fiber basal lamina, also induces AChR clustering. We find that induction of AChR clustering in C2 myotubes is specific for laminin-1, neither laminin-2 (merosin) nor laminin-11 (a synapse-specific isoform) are active. Moreover, laminin-1 induces AChR clustering by a pathway that is independent of that used by neural agrin. The effects of laminin-1 and agrin are strictly additive and occur with different time courses. Most importantly, laminin 1-induced clustering does not require MuSK, a receptor tyrosine kinase that is part of the receptor complex for agrin. Laminin-1 does not cause tyrosine phosphorylation of MuSK in C2 myotubes and induces AChR clustering in myotubes from MuSK-/- mice that do not respond to agrin. In contrast to agrin, laminin-1 also does not induce tyrosine phosphorylation of the AChR, demonstrating that AChR tyrosine phosphorylation is not required for clustering in myotubes. Laminin-1 thus acts by a mechanism that is independent of that used by agrin and may provide a supplemental pathway for AChR clustering during synaptogenesis. C1 NIMH,NIH,BETHESDA,MD 20892. REGENERON PHARMACEUT INC,TARRYTOWN,NY 10591. NR 58 TC 108 Z9 108 U1 1 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD OCT 6 PY 1997 VL 139 IS 1 BP 181 EP 191 DI 10.1083/jcb.139.1.181 PG 11 WC Cell Biology SC Cell Biology GA YB446 UT WOS:A1997YB44600015 PM 9314538 ER PT J AU Snyder, HL Bacik, I Bennink, JR Kearns, G Behrens, TW Bachi, T Orlowski, M Yewdell, JW AF Snyder, HL Bacik, I Bennink, JR Kearns, G Behrens, TW Bachi, T Orlowski, M Yewdell, JW TI Two novel routes of transporter associated with antigen processing (TAP)-independent major histocompatibility complex class I antigen processing SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MULTICATALYTIC PROTEINASE COMPLEX; CYTOTOXIC LYMPHOCYTES-T; RMA-S CELLS; ENDOPLASMIC-RETICULUM; MUTANT-CELLS; PEPTIDES; MOLECULES; PROTEASOME; INHIBITION; TAP AB Jaw1 is an endoplasmic reticulum (ER) resident protein representative of a class of proteins post translationally inserted into membranes via a type II membrane anchor (cytosolic NH2 domain, lumenal COOH domain) in a translocon-independent manner. We found that Jaw1 can efficiently deliver a COOH-terminal antigenic peptide to class I molecules in transporter associated with antigen processing (TAP)-deficient cells or cells in which TAP is inactivated by the ICP47 protein. Peptide delivery mediated by Jaw1 to class I molecules was equal or better than that mediated by the adenovirus E3/19K glycoprotein signal sequence, and was sufficient to enable cytofluorographic detection of newly recruited thermostabile class I molecules at the surface of TAP-deficient cells. Deletion of the transmembrane region retargeted Jaw1 from the ER to the cytosol, and severely, although incompletely, abrogated its TAP-independent peptide carrier activity. Use of different protease inhibitors revealed the involvement of a nonproteasomal protease in the TAP-independent activity of cytosolic Jaw1. These findings demonstrate two novel TAP-independent routes of antigen processing; one based on highly efficient peptide liberation from the COOH terminus of membrane proteins in the ER, the other on delivery of a cytosolic protein to the ER by an unknown route. C1 NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892. UNIV MINNESOTA,DEPT MED,MINNEAPOLIS,MN 55455. UNIV ZURICH,ELECTRON MICROSCOPY LAB,CH-8091 ZURICH,SWITZERLAND. CUNY MT SINAI SCH MED,DEPT PHARMACOL,NEW YORK,NY 10029. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 48 TC 71 Z9 75 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 OCT 6 PY 1997 VL 186 IS 7 BP 1087 EP 1098 DI 10.1084/jem.186.7.1087 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA YA580 UT WOS:A1997YA58000011 PM 9314557 ER PT J AU Gurunathan, S Sacks, DL Brown, DR Reiner, SL Charest, H Glaichenhaus, N Seder, RA AF Gurunathan, S Sacks, DL Brown, DR Reiner, SL Charest, H Glaichenhaus, N Seder, RA TI Vaccination with DNA encoding the immunodominant LACK parasite antigen confers protective immunity to mice infected with Leishmania major SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MURINE CUTANEOUS LEISHMANIASIS; INTERFERON-GAMMA PRODUCTION; CD8+ T-CELLS; PLASMID DNA; BACTERIAL-DNA; BALB/C MICE; CPG MOTIFS; IMMUNIZATION; INTERLEUKIN-12; INDUCTION AB To determine whether DNA immunization could elicit protective immunity to Leishmania major in susceptible BALB/c mice, cDNA for the cloned Leishmania antigen LACK was inserted into a euykaryotic expression vector downstream to the cytomegalovirus promoter. Susceptible BALB/c mice were then vaccinated subcutaneously with LACK DNA and challenged with L. major promastigotes. We compared the protective efficacy of LACK DNA vaccination with that of recombinant LACK protein in the presence or absence of recombinant interleukin (rIL)-12 protein. Protection induced by LACK DNA was similar to that achieved by LACK protein and rIL-12, but superior to LACK protein without rIL-12. The immunity conferred by LACK DNA was durable insofar as mice challenged 5 wk after vaccination were still protected, and the infection was controlled for at least 20 wk after challenge. In addition, the ability of mice to control infection at sites distant to the site of vaccination suggests that systemic protection was achieved by LACK DNA vaccination. The control of disease progression and parasitic burden in mice vaccinated with LACK DNA was associated with enhancement of antigen-specific interferon-gamma (IFN-gamma) production. Moreover, both the enhancement of IFN-gamma production and the protective immune response induced by LACK DNA vaccination was IL-12 dependent. Unexpectedly, depletion of CD8(+) T cells at the time of vaccination or infection also abolished the protective response induced by LACK DNA vaccination, suggesting a role for CD8(+) T cells in DNA vaccine induced protection to L. major. Thus, DNA immunization may offer an attractive alternative vaccination strategy against intracellular pathogens, as compared with conventional vaccination with antigens combined with adjuvants. C1 NIAID,LYMPHOKINE REGULAT UNIT,CLIN INVEST LAB,NIH,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. UNIV CHICAGO,DEPT MED,COMM IMMUNOL,CHICAGO,IL 60637. UNIV CHICAGO,GWEN KANPP CTR LUPUS & IMMUNOL RES,CHICAGO,IL 60637. CNRS,INST PHARMACOL MOL & CELLULAIRE,UPR 411,F-06560 VALBONNE,FRANCE. FU NIAID NIH HHS [AI-01309] NR 54 TC 259 Z9 266 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 OCT 6 PY 1997 VL 186 IS 7 BP 1137 EP 1147 DI 10.1084/jem.186.7.1137 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA YA580 UT WOS:A1997YA58000016 PM 9314562 ER PT J AU Wang, J Lenardo, MJ AF Wang, J Lenardo, MJ TI Essential lymphocyte function associated 1 (LFA-1): Intercellular adhesion molecule interactions for T cell-mediated B cell apoptosis by Fas/APO-1/CD95 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID LYMPHOPROLIFERATIVE SYNDROME; ANTIGEN RECEPTOR; IMMUNE-RESPONSES; COUNTER-RECEPTOR; FAS LIGAND; MUTATIONS; MICE; ELIMINATION; EXPRESSION; ACTIVATION AB B cells are susceptible to Fas ligand (FasL)(+) CD4(+) Th1 cell-mediated apoptosis. We demonstrate that blocking the interactions between lymphocyte function associated (LFA)-1 and intercellular adhesion molecule(ICAM)-1 and ICAM-2 completely suppresses Fas-dependent B cell lysis. Antibodies to CD2 and CD48 partially suppress B cell apoptosis, whereas anti-B7.1 and anti-B7.2 antibodies have no effect. Also, B cells from ICAM-1-deficient mice are resistant to FasL(+) T cell-mediated death. Our results suggest that LFA-1/ICAM interactions are crucial for Th1 cell-mediated B cell apoptosis and may contribute to the maintenance of B cell homeostasis in vivo. C1 NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NR 26 TC 38 Z9 40 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 OCT 6 PY 1997 VL 186 IS 7 BP 1171 EP 1176 DI 10.1084/jem.186.7.1171 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA YA580 UT WOS:A1997YA58000020 PM 9314566 ER PT J AU Feng, ZH Zhang, WQ Hudson, P Bing, GY Feng, W Hong, JS AF Feng, ZH Zhang, WQ Hudson, P Bing, GY Feng, W Hong, JS TI Characterization of the long-lasting activator protein-1 complex induced by kainic acid treatment SO BRAIN RESEARCH LA English DT Article DE transcription factor; Fra; Jun-D; hippocampus; kainic acid; seizure; AP-1 ID KAINATE-INDUCED CHANGES; DNA-BINDING ACTIVITY; FOS-LIKE PROTEINS; C-FOS; RAT HIPPOCAMPUS; INDUCED SEIZURES; TRANSCRIPTION FACTORS; GENE-EXPRESSION; CHRONIC COCAINE; AP-1 COMPLEX AB Kainic acid is known to induce seizures, neuronal damage and cell loss in the rat hippocampus. Our laboratory has shown that a single kainic acid injection elicits acute increases of activator protein-1 DNA-binding activity and this activity stays at an elevated level for 2 weeks after kainic acid injection. However, some pathological changes such as messy fiber sprouting do not occur until 2-3 weeks after the kainic acid injection and the specific transcription factors regulating the long-term events after kainic acid treatment are not clear. To determine the involvement of activator protein-1 transcription factors in the long-term events after kainic acid treatment, gel mobility-shift and Western blot analyses were used. The results showed that two activator protein-1 complexes with different mobilities occur during the acute stage. However, only the faster-migrating complex as well as the 35-37-kDa fos-related antigen and Jun-D proteins were seen during the late stage. These results suggest that different activator protein-1 complexes exist at different stages after convulsions and that they regulate ensembles of different genes. (C) 1997 Elsevier Science B.V. RP Feng, ZH (reprint author), NIEHS, NEUROPHARMACOL SECT,TOXICOL LAB,NIH,POB 12233, MD F1-01, RES TRIANGLE PK, NC 27709 USA. OI Bing, Guoying/0000-0003-0609-8152 NR 33 TC 16 Z9 18 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 OCT 3 PY 1997 VL 770 IS 1-2 BP 53 EP 59 DI 10.1016/S0006-8993(97)00744-0 PG 7 WC Neurosciences SC Neurosciences & Neurology GA YC745 UT WOS:A1997YC74500008 PM 9372202 ER PT J AU Mann, H McCoy, MT Subramaniam, J VanRemmen, H Cadet, JL AF Mann, H McCoy, MT Subramaniam, J VanRemmen, H Cadet, JL TI Overexpression of superoxide dismutase and catalase in immortalized neural cells: toxic effects of hydrogen peroxide SO BRAIN RESEARCH LA English DT Article DE hydrogen peroxide; superoxide dismutase; catalase; cytotoxicity ID CULTURED CARDIAC MYOCYTES; CENTRAL-NERVOUS-SYSTEM; INDUCED DNA DAMAGE; OXIDATIVE STRESS; OXYGEN RADICALS; DEATH; CYTOTOXICITY; IRON; 6-HYDROXYDOPAMINE; ENDONUCLEASE AB Hydrogen peroxide (H2O2) is a known toxicant which causes its damage via the production of hydroxyl radicals. It has been reported to cause both necrotic and apoptotic cell death. The present study was undertaken to evaluate the mode of H2O2-induced cell death and to assess if overexpression of catalase could protect against its toxicity. H2O2 causes cell death of immortalized CSM 14.1 neural cells in a dose-dependent manner. H2O2-induced death was associated with DNA laddering as shown by agarose gel electrophoresis. Stable overexpression of catalase by transfection of a vector containing human cDNA into these cells markedly attenuated H2O2-induced toxic effects. Transfection of a vector containing a SOD cDNA afforded no protection. These results indicate that H2O2 can lead to the activation of endonuclease enzyme that breaks DNA into oligosomes. These cells which overexpress catalase or SOD will help to determine the specific role of H2O2 or O-2(radical anion) in the deleterious effects of a number of toxins. (C) 1997 Elsevier Science B.V. C1 NIDA, IRP, MOL NEUROPSYCHIAT SECT, NIH, BALTIMORE, MD 21224 USA. ALMMVAH, DEPT PHYSIOL, GRECC 182, SAN ANTONIO, TX USA. NR 50 TC 23 Z9 23 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD OCT 3 PY 1997 VL 770 IS 1-2 BP 163 EP 168 DI 10.1016/S0006-8993(97)00768-3 PG 6 WC Neurosciences SC Neurosciences & Neurology GA YC745 UT WOS:A1997YC74500021 PM 9372215 ER PT J AU Ichikawa, H Jacobowitz, DM Sugimoto, T AF Ichikawa, H Jacobowitz, DM Sugimoto, T TI Coexpression of calretinin and parvalbumin in Ruffini-like endings in the rat incisor periodontal ligament SO BRAIN RESEARCH LA English DT Article DE calretinin; immunohistochemistry; incisor; parvalbumin; periodontal ligament; Ruffini-like ending; trigeminal ganglion ID TRIGEMINAL NEURONS; IMMUNOHISTOCHEMICAL LOCALIZATION; SENSORY NEURONS; TOOTH-PULP; IMMUNOREACTIVITY; INNERVATION; PROTEIN; BRAIN; CAT AB The coexpression of calretinin-(CR) and parvalbumin-immunoreactivities (irs) was examined in ore-facial tissues of the rat. Nerve fibers coexpressing these calcium-binding proteins (CaBPs) were observed in the lingual periodontal ligament of incisors but not other tissues. In the part of periodontal ligament adjacent to the alveolar bone, such nerve fibers left nerve bundles and formed bush-like endings, i.e., they ramified repeatedly and terminated with one to four twigs. An immunoelectron microscopic method indicated that these endings were identical to Ruffini-like endings. 4% of trigeminal neurons retrogradely labeled from the inferior alveolar nerve coexpressed CR-and parvalbumin-irs. The present observations suggest that the coexpression of these CaBPs may be a specific marker for low-threshold mechanoreceptors in the trigeminal ganglion. (C) 1997 Elsevier Science B.V. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RP Ichikawa, H (reprint author), OKAYAMA UNIV,SCH DENT,DEPT ORAL ANAT 2,2-5-1 SHIKATA CHO,OKAYAMA 700,JAPAN. NR 18 TC 43 Z9 43 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 OCT 3 PY 1997 VL 770 IS 1-2 BP 294 EP 297 DI 10.1016/S0006-8993(97)00826-3 PG 4 WC Neurosciences SC Neurosciences & Neurology GA YC745 UT WOS:A1997YC74500038 PM 9372232 ER PT J AU Guacci, V Koshland, D Strunnikov, A AF Guacci, V Koshland, D Strunnikov, A TI A direct link between sister chromatid cohesion and chromosome condensation revealed through the analysis of MCD1 in S-cerevisiae SO CELL LA English DT Article ID UBIQUITOUS PROTEIN FAMILY; SACCHAROMYCES-CEREVISIAE; BUDDING YEAST; CELL-CYCLE; FISSION YEAST; SCHIZOSACCHAROMYCES-POMBE; GENE; DNA; MITOSIS; PROTEOLYSIS AB The S. cerevisiae MCD1 (mitotic chromosome determinant) gene was identified in genetic screens for genes important for chromosome structure. MCD1 is essential for viability and homologs are found from yeast to humans. Analysis of the mcd1 mutant and cell cycle-dependent expression pattern of Mcd1p suggest that this protein functions in chromosome morphogenesis from S phase through mitosis. The mcd1 mutant is defective in sister chromatid cohesion and chromosome condensation. The physical association between Mcd1p and Smc1p, one of the SMC family of chromosomal proteins, further suggests that Mcd1p functions directly on chromosomes. These data implicate Mcd1p as a nexus between cohesion and condensation. We present a model for mitotic chromosome structure that incorporates this previously unsuspected link. C1 NICHHD,UNIT CHROMOSOME STRUCT & FUNCT,NIH,MOL EMBRYOL LAB,BETHESDA,MD 20892. RP Guacci, V (reprint author), CARNEGIE INST WASHINGTON,DEPT EMBRYOL,HOWARD HUGHES MED INST,115 W UNIV PKWY,BALTIMORE,MD 21210, USA. OI Strunnikov, Alexander/0000-0002-9058-2256 FU Intramural NIH HHS [Z01 HD001903-11, Z99 AI999999]; NIGMS NIH HHS [GM41718] NR 53 TC 549 Z9 556 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD OCT 3 PY 1997 VL 91 IS 1 BP 47 EP 57 DI 10.1016/S0092-8674(01)80008-8 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XZ809 UT WOS:A1997XZ80900008 PM 9335334 ER PT J AU Hall, TMT Porter, JA Young, KE Koonin, EV Beachy, PA Leahy, DJ AF Hall, TMT Porter, JA Young, KE Koonin, EV Beachy, PA Leahy, DJ TI Crystal structure of a hedgehog autoprocessing domain: Homology between hedgehog and self-splicing proteins SO CELL LA English DT Article ID TERMINAL CLEAVAGE PRODUCT; SONIC HEDGEHOG; AUTOPROTEOLYTIC CLEAVAGE; CIRCULAR PERMUTATIONS; ANOMALOUS DIFFRACTION; PATTERNING ACTIVITY; XENOPUS-LAEVIS; INDUCTION; ALIGNMENT; SEQUENCE AB The similar to 25 kDa carboxy-terminal domain of Drosophila Hedgehog protein (Hh-C) possesses an autoprocessing activity that results in an intramolecular cleavage of full-length Hedgehog protein and covalent attachment of a cholesterol moiety to the newly generated amino-terminal fragment. We have identified a 17 kDa fragment of Hh-C (Hh-C-17) active in the initiation of autoprocessing and report here its crystal structure. The Hh-C-17 structure comprises two homologous subdomains that appear to have arisen from tandem duplication of a primordial gene. Residues in the Hh-C-17 active site have been identified, and their role in Hedgehog autoprocessing probed by site-directed mutagenesis. Aspects of sequence, structure, and reaction mechanism are conserved between Hh-C-17 and the self-splicing regions of inteins, permitting reconstruction of a plausible evolutionary history of Hh-C and the inteins. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT BIOPHYS & BIOPHYS CHEM,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MOL BIOL & GENET,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,HOWARD HUGHES MED INST,BALTIMORE,MD 21205. NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20894. NR 51 TC 175 Z9 182 U1 0 U2 10 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD OCT 3 PY 1997 VL 91 IS 1 BP 85 EP 97 DI 10.1016/S0092-8674(01)80011-8 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XZ809 UT WOS:A1997XZ80900011 PM 9335337 ER PT J AU Orford, K Crockett, C Jensen, JP Weissman, AM Byers, SW AF Orford, K Crockett, C Jensen, JP Weissman, AM Byers, SW TI Serine phosphorylation-regulated ubiquitination and degradation of beta-catenin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3; TUMOR-SUPPRESSOR PROTEIN; SIGNAL-TRANSDUCTION; XENOPUS EMBRYOS; CELL-ADHESION; ARMADILLO; PATHWAY; STABILITY; COMPLEX; INSULIN AB Several lines of evidence suggest that accumulation of cytoplasmic beta-catenin transduces an oncogenic signal We show that beta-catenin is ubiquitinated and degraded by the proteosome and that beta-catenin stability is regulated by a diacylglycerol-independent protein kinase C-like kinase activity, which is required for beta-catenin ubiquitination. We also define a sis-amino acid sequence found in both beta-catenin and the NF-kappa B regulatory protein I kappa B alpha, which, upon phosphorylation, targets both proteins for ubiquitination. Mutation of a single serine within the ubiquitination targeting sequence prevents ubiquitination of beta-catenin. Mutations within the ubiquitination targeting sequence of beta-catenin may be oncogenic. C1 GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. NCI,DCBD,NIH,BETHESDA,MD 20892. NR 29 TC 539 Z9 550 U1 2 U2 6 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 OCT 3 PY 1997 VL 272 IS 40 BP 24735 EP 24738 DI 10.1074/jbc.272.40.24735 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XY970 UT WOS:A1997XY97000003 PM 9312064 ER PT J AU Ascoli, GA Luu, KX Olds, JL Nelson, TJ Gusev, PA Bertucci, C Bramanti, E Raffaelli, A Salvadori, P Alkon, DL AF Ascoli, GA Luu, KX Olds, JL Nelson, TJ Gusev, PA Bertucci, C Bramanti, E Raffaelli, A Salvadori, P Alkon, DL TI Secondary structure and Ca2+-induced conformational change of calexcitin, a learning-associated protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTP-BINDING PROTEIN; CALCIUM-MODULATED PROTEINS; EF-HAND; CIRCULAR-DICHROISM; KINASE-C; MOLECULAR MECHANISMS; STRUCTURE PREDICTION; POTASSIUM CHANNELS; ESCHERICHIA-COLI; MEMORY STORAGE AB Calexcitin/cp20 is a low molecular weight GTP- and Ca2+-binding protein, which is phosphorylated by protein kinase C during associative learning, and reproduces many of the cellular effects of learning, such as the reduction of potassium currents in neurons, Here, the secondary structure of cloned squid calexcitin was determined by circular dichroism in aqueous solution and by Fourier transform infrared spectroscopy both in solution and on dried films, The results obtained with the two techniques are in agreement with each other and coincide with the secondary structure computed from the amino acid sequence, In solution, calexcitin is one-third in alpha-helix and one-fifth in beta-sheet. The conformation of the protein in solid state depends on the concentration of the starting solution, suggesting the occurrence of surface aggregation. The secondary structure also depends on the binding of calcium, which causes an increase in alpha-helix and a decrease in beta-sheet, as estimated by circular dichroism, The conformation of calexcitin is independent of ionic strength, and the calcium-induced structural transition is slightly inhibited by Mg2+ and low pH, while favored by high pH. The switch of calexcitin's secondary structure upon calcium binding, which was confirmed by intrinsic fluorescence spectroscopy and nondenaturing gel electrophoresis, is reversible and occurs in a physiologically meaningful range of Ca2+ concentration. The calcium-bound form is more globular than the apoprotein, Unlike other EF-hand proteins, calexcitin's overall lipophilicity is not affected by calcium binding, as assessed by hydrophobic liquid chromatography. Preliminary results from patch-clamp experiments indicated that calcium is necessary for calexcitin to inhibit potassium channels and thus to increase membrane excitability, Therefore the calcium-dependent conformational equilibrium of calexcitin could serve as a molecular switch for the short term modulation of neuronal activity following associative conditioning. C1 UNIV PISA,DIPARTIMENTO CHIM & CHIM IND,CNR,CTR STUDIO MACROMOL STEREORDINATE & OTTICAMENTE,I-56126 PISA,ITALY. CNR,INST INSTRUMENTAL ANALYT CHEM,I-56126 PISA,ITALY. RP Ascoli, GA (reprint author), NINCDS,LAS,NIH,BLDG 36,RM 4A24,35 CONVENT DR MSC 4124,BETHESDA,MD 20892, USA. RI Olds, James/D-2867-2011; Bramanti, Emilia/E-1114-2011 OI Bramanti, Emilia/0000-0001-8478-7370 NR 53 TC 25 Z9 25 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 OCT 3 PY 1997 VL 272 IS 40 BP 24771 EP 24779 DI 10.1074/jbc.272.40.24771 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XY970 UT WOS:A1997XY97000012 PM 9312073 ER PT J AU Ueda, H Siani, MA Gong, WH Thompson, DA Brown, GG Wang, JM AF Ueda, H Siani, MA Gong, WH Thompson, DA Brown, GG Wang, JM TI Chemically synthesized SDF-1 alpha analogue, N33A, is a potent chemotactic agent for CXCR4/Fusin/LESTR-expressing human leukocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-3 MCP3 INTERACTS; MOLECULAR-CLONING; CHEMOKINE RECEPTORS; HIV-1 ENTRY; LYMPHOCYTE CHEMOATTRACTANT; CHROMOSOMAL LOCALIZATION; 7-TRANSMEMBRANE; RANTES; SDF-1; GENE AB Stromal cell-derived factor (SDF) 1 is a potent chemoattractant for leukocytes through activation of the receptor CXCR4/Fusin/LESTR, which is a fusion co-factor for the entry of T lymphocytotropic human immunodeficiency virus type 1 (HIV-1), This CXCR4-mediated HIV-1 fusion can be inhibited by SDF-1, Because of its importance in the study of immunity and AIDS, large scale production of SDF-1 is desirable, In addition to recombinant technology, chemical synthesis provides means by which biologically active proteins can be produced not only in large quantity but also with a variety of designed modifications, In this study, we investigated the binding and function of an SDF-1 alpha analogue, N33A, synthesized by a newly developed native chemical ligation approach, Radioiodinated N33A showed high affinity binding to human monocytes, T lymphocytes, as well as neutrophils, and competed equally well with native recombinant SDF-1 alpha for binding sites on leukocytes. N33A also showed equally potent chemoattractant activity as native recombinant SDF-1 alpha for human leukocytes. Further study with CXCR4/Fusin/LESTR transfected HEK 293 cells showed that N33A binds and induces directional migration of these cells in vitro. These results demonstrate that the chemically synthesized SDF-1 alpha analogue, N33A, which can be produced rapidly in large quantity, possesses the same capacity as native SDF-1 alpha to activate CXCR4-expressing cells and will provide a valuable agent for research on the host immune response and AIDS. C1 NCI,FREDERICK CANC RES & DEV CTR,MOL IMMUNOREGULAT LAB,DIV BASIC SCI,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,INTRAMURAL RES SUPPORTPROGRAM,SAIC FREDRICK,FREDERICK,MD 21702. GRYPHON SCI,S SAN FRANCISCO,CA 94080. NEN LIFE SCI PROD,IODINAT GRP,BILLERICA,MA 01862. NR 33 TC 57 Z9 58 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 OCT 3 PY 1997 VL 272 IS 40 BP 24966 EP 24970 DI 10.1074/jbc.272.40.24966 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XY970 UT WOS:A1997XY97000040 PM 9312101 ER PT J AU Vitale, N Moss, J Vaughan, M AF Vitale, N Moss, J Vaughan, M TI Characterization of a GDP dissociation inhibitory region of ADP-ribosylation factor domain protein ARD1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTPASE-ACTIVATING PROTEIN; NUCLEOTIDE-EXCHANGE PROTEIN; GUANINE-NUCLEOTIDE; BREFELDIN-A; CHOLERA-TOXIN; BINDING-PROTEIN; AMINO-TERMINUS; FACTOR ARF; FACTOR-I; GOLGI AB ADP-ribosylation factors (ARFs) are similar to 20-kDa guanine nucleotide-binding proteins initially identified by their ability to stimulate cholera toxin ADP ribosyltransferase activity and later recognized as critical components in intracellular vesicular transport and phospholipase D activation, ARF domain protein 1 (ARD1) is a member of the ARF family that differs from other ARFs by the presence of a 46-kDa amino-terminal extension, We previously reported that this extension acts as a GTPase-activating protein for the ARF domain of ARD1 (Vitale, N., Moss, J., and Vaughan, M. (1996) Proc, Natl, Acad, Sci. U. S. A. 93, 1941-1944), Both GTP binding and GTP hydrolysis are necessary for physiological function of guanine nucleotide binding proteins, and the rates of GDP/GTP exchange and GTPase activity are critical in the activation/deactivation cycle. Dissociation of GDP from the ARF domain of ARD1 was faster than from ARD1 itself (both proteins synthesized in Escherichia coli). Using deletion mutations, it was demonstrated that the 15 amino acids directly preceding the ARF domain were responsible for decreasing the rate of GDP dissociation but not guanosine 5-[gamma-thio]triphosphate dissociation, By site specific mutagenesis it was shown that hydrophobic amino acids in this region were particularly important in stabilizing the GDP-bound form of ARD1. It is suggested that, Like the amino-terminal segment of ARF, the equivalent region in ARD1, located between the GTPase activating protein and ARF domains, may act as a GDP dissociation inhibitor. RP Vitale, N (reprint author), NHLBI,PULM CRIT CARE MED BRANCH,NIH,RM 5N-307,BLDG 10,10 CTR DR,MSC 1434,BETHESDA,MD 20892, USA. RI Vitale, nicolas/G-5967-2014 OI Vitale, nicolas/0000-0002-4752-4907 NR 35 TC 9 Z9 9 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 OCT 3 PY 1997 VL 272 IS 40 BP 25077 EP 25082 DI 10.1074/jbc.272.40.25077 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XY970 UT WOS:A1997XY97000055 PM 9312116 ER PT J AU Silver, DL Vorotnikov, AV Watterson, DM Shirinsky, VP Sellers, JR AF Silver, DL Vorotnikov, AV Watterson, DM Shirinsky, VP Sellers, JR TI Sites of interaction between kinase-related protein and smooth muscle myosin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LIGHT-CHAIN KINASE; C-PROTEIN; HEAVY-MEROMYOSIN; SKELETAL-MUSCLE; CARBOXYL-TERMINUS; 10S CONFORMATION; CHICKEN GIZZARD; MYBP-C; BINDING; PHOSPHORYLATION AB Kinase-related protein, also known as KRP or telokin, is an independently expressed protein product derived from a gene within the gene for myosin light chain kinase (MLCK). KRP binds to unphosphorylated smooth muscle myosin filaments and stabilizes them against ATP-induced depolymerization in vitro. KRP competes with MLCK for binding to myosin, suggesting that both proteins bind to myosin by the KRP domain (Shirinsky, V. P., Vorotnikov, A. V., Birukov, K. G., Nanaev, A. K., Collinge, M., Lukas, T. J., Sellers, J. R., and Watterson, D. M. (1993) J. Biol. Chem. 268, 16578-16583). In this study, we investigated which regions of myosin and KRP interact in vitro. Using cosedimentation assays, we determined that HRP binds to unphosphorylated myosin with a stoichiometry of 1 mol of KRP/1 mol of myosin and an affinity of 5.5 mu m. KRP slows the rate of proteolytic cleavage of the head-tail junction of heavy meromyosin by papain and chymotrypsin, suggesting it is binding to this region of myosin. In addition, competition experiments, using soluble headless fragments of nonmuscle myosin, confirmed that KRP interacts with the regulatory light chain binding region of myosin. The regions important for KRP's binding to myosin were investigated using bacterially expressed KRP truncation mutants. We determined that the acid-rich sequence between Gly(138) and Asp(151) of KRP is required for high affinity myosin binding, and that the amino terminus and beta-barrel regions weakly interact with myosin. All KRP truncations, at concentrations comparable to their K-D values, exhibited some stabilization of myosin filaments against ATP depolymerization in vitro, suggesting that KRP's ability to stabilize myosin filaments is commensurate with its myosin binding affinity. HRP weakened the K-m but not the V-max of phosphorylation of myosin by MLCK, demonstrating that bound HRP does not prevent MLCK from activating myosin. C1 NHLBI,MOL CARDIOL LAB,BETHESDA,MD 20892. RUSSIAN ACAD MED SCI,CARDIOL RES CTR,INST EXPT CARDIOL,MOL ENDOCRINOL LAB,MOSCOW 121552,RUSSIA. NORTHWESTERN UNIV,DRUG DISCOVERY PROGRAM,CHICAGO,IL 60611. NORTHWESTERN UNIV,DEPT BIOL CHEM & MOL PHARMACOL,CHICAGO,IL 60611. RI Vorotnikov, Alexander/A-8392-2014; OI Vorotnikov, Alexander/0000-0002-1460-971X; Watterson, Daniel/0000-0001-7605-5866 FU NIGMS NIH HHS [GM30861] NR 44 TC 45 Z9 46 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 OCT 3 PY 1997 VL 272 IS 40 BP 25353 EP 25359 DI 10.1074/jbc.272.40.25353 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XY970 UT WOS:A1997XY97000094 PM 9312155 ER PT J AU Pellegrino, S Zhang, SY Garritsen, A Simonds, WF AF Pellegrino, S Zhang, SY Garritsen, A Simonds, WF TI The coiled-coil region of the G protein beta subunit - Mutational analysis of G gamma and effector interactions SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HETEROTRIMERIC G-PROTEINS; DIEKER LISSENCEPHALY GENE; GCN4 LEUCINE-ZIPPER; CRYSTAL-STRUCTURE; COMPLEX-FORMATION; KINASE PATHWAY; DOMAIN; ACTIVATION; BINDING; MITOGEN AB The beta and gamma subunits of the heterotrimeric G proteins remain tightly associated throughout the signaling cycle as the beta gamma dimer interacts with G alpha, receptors, and effecters, A coiled coil structure involving alpha-helical segments at the N termini of the beta and gamma subunits contrib- utes to the dimerization interface and has been implicated in effector signaling in yeast, Scanning mutagenesis of the coiled-coil region of the mammalian beta(1) subunit was performed to examine the effect of point mutations on py assembly and effector signaling in COS cell cotransfection assays, In addition to the E10K mutation described previously mutations A11E, L14E, and I18E in beta(1) were found to block beta gamma association, as evidenced by the failure of the G beta mutants to undergo cytosolic translocation with cotransfected nonisoprenylated G gamma, Although none of 14 beta(1) point mutations prevented the beta gamma-dependent activation of the c-Jun N-terminal kinase (JNK) effector pathway, the D20K point mutation enhanced JNK but not phospholipase C-beta 2 activation, These findings implicate the coiled-coil region of G beta in JNK signaling, provide further evidence that the structural features of the beta gamma complex mediating effector regulation may differ among effecters, and identify single codons in the mammalian beta subunit where mutation might yield a phenotype of defective signal transduction. C1 NIDDK,METAB DIS BRANCH,NIH,BETHESDA,MD 20892. NR 63 TC 23 Z9 24 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 OCT 3 PY 1997 VL 272 IS 40 BP 25360 EP 25366 DI 10.1074/jbc.272.40.25360 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XY970 UT WOS:A1997XY97000095 PM 9312156 ER PT J AU Takahashi, N Uhl, G AF Takahashi, N Uhl, G TI Murine vesicular monoamine transporter 2: molecular cloning and genomic structure SO MOLECULAR BRAIN RESEARCH LA English DT Article DE vesicular monoamine transporter (VMAT2); cDNA; gene; promoter; amphetamine; N-methyl-1,2,3,6-tetrahydropyridine ID NEURON-SPECIFIC EXPRESSION; DOPAMINE TRANSPORTER; CHROMAFFIN GRANULES; NEUROTRANSMITTER TRANSPORTERS; AMINE TRANSPORTER; PROMOTER REGION; RECEPTOR GENE; PARKINSONISM; MECHANISM; CELLS AB The principal brain vesicular monoamine transporter (VMAT2) pumps monoamines including dopamine, norepinephrine, serotonin and histamine from neuronal cytoplasm into synaptic vesicles and is implicated in actions of certain psychostimulants and selective neurotoxins. To improve understanding of this gene and its regulation, and to facilitate study of the roles played by this important molecule in mouse genetic models, we have cloned murine VMAT2 cDNA and genomic sequences. A 4.2-kb mouse VMAT2 cDNA hybridized to a 4.3-kb mRNA expressed chiefly in brainstem. Murine cDNA and genomic DNA analyses reveal an open reading frame of 1551 bp encoding 517 amino acids that display 92, 96 and 60% amino-acid identity with human and rat VMAT2, and rat vesicular acetylcholine transporter sequences, respectively. This open reading frame is distributed over 15 of 16 identified exons, and spans > 35 kb of genomic DNA. A major transcriptional initiation site is identified 107 bp 5' to the translational initiation ATG codon using primer extension/5' rapid amplification of cDNA ends. Sequences immediately 5' of this putative transcription start site lack 'TATA' or 'CATT' boxes, but contain consensus sequences that may bind cAMP response element, Spl, AP2 and other transcription factors. Identification of these genomic sequences facilitates construction of homologous recombinant mice, provides a template for gene structures in the vesicular transporter family, and identifies sequences elements that could contribute to the specific patterns of regulated VMAT2 expression in monoaminergic neurons. (C) 1997 Elsevier Science B.V. C1 NIDA,MOL NEUROBIOL BRANCH,INTRAMURAL RES PROGRAM,NIH,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. NR 45 TC 25 Z9 26 U1 1 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 OCT 3 PY 1997 VL 49 IS 1-2 BP 7 EP 14 DI 10.1016/S0169-328X(97)00116-2 PG 8 WC Neurosciences SC Neurosciences & Neurology GA YC769 UT WOS:A1997YC76900002 PM 9387858 ER PT J AU Strauss, KI Kuznicki, J Winsky, L Kawagoe, JI Hammer, M Jacobowitz, DM AF Strauss, KI Kuznicki, J Winsky, L Kawagoe, JI Hammer, M Jacobowitz, DM TI The mouse calretinin gene promoter region: structural and functional components SO MOLECULAR BRAIN RESEARCH LA English DT Article DE calretinin gene; neuron-restrictive promoter; luciferase transfection; embryonic mouse brain primary culture ID CALCIUM-BINDING PROTEIN; NF-KAPPA-B; ROOT GANGLION NEURONS; RAT CALRETININ; IMMUNOHISTOCHEMICAL LOCALIZATION; CONFORMATIONAL-CHANGES; TYROSINE-HYDROXYLASE; TRANSGENE EXPRESSION; REGULATORY ELEMENTS; NUCLEOTIDE-SEQUENCE AB The 5' flanking region of the mouse calretinin gene was cloned and a 1.8 kbp region adjacent to exon I was sequenced. Putative upstream promoter and enhancer elements were identified, including appropriately positioned TATA and CAAT boxes (positions -50 and -68, respectively). There was considerable sequence and structural homolog between mouse and human upstream elements. Neuron-restrictive activity was demonstrated via transfection of calretinin promoter-reporter constructs into primary embryonic mouse brain cultures expressing calretinin. In promoterless reporter constructs, the proximal upstream 1.5 kbp of the mouse calretinin gene boosted luciferase activity (up to 100-fold) exclusively in the neuronal population. Deletion analysis revealed the minimal promoter to be within the 95-bp proximal to the transcription start site. Transfections with SV40 promoter constructs in these cultures resulted in reporter gene expression predominantly in non-neuronal cells. Inserting the proximal 1.5 kbp of mouse calretinin upstream in SV40 promoter-reporter constructs reduced luciferase activity. Thus, calretinin upstream sequences increased reporter expression in cultured neurons and decreased expression from the SV40 promoter in non-neuronal cultured brain cells. The calretinin promoter contained relevant regulatory element consensus motifs and demonstrated in vitro neuron-restrictive bioactivity. (C) 1997 Elsevier Science B.V. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NR 55 TC 9 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD OCT 3 PY 1997 VL 49 IS 1-2 BP 175 EP 187 DI 10.1016/S0169-328X(97)00143-5 PG 13 WC Neurosciences SC Neurosciences & Neurology GA YC769 UT WOS:A1997YC76900021 PM 9387877 ER PT J AU Leshner, AI AF Leshner, AI TI Addiction is a brain disease, and it matters SO SCIENCE LA English DT Article ID INJECTION-DRUG USERS; MOLECULAR MECHANISMS; COCAINE; ABUSE; ADAPTATIONS; BEHAVIOR; PATHWAYS; EXPOSURE; SYSTEM AB Scientific advances over the past 20 years have shown that drug addiction is a chronic, relapsing disease that results from the prolonged effects of drugs on the brain. As with many other brain diseases, addiction has embedded behavioral and social-context aspects that are important parts of the disorder itself. Therefore, the most effective treatment approaches will include biological, behavioral, and social-context components. Recognizing addiction as a chronic, relapsing brain disorder characterized by compulsive drug seeking and use can impact society's overall health and social policy strategies and help diminish the health and social costs associated with drug abuse and addiction. RP Leshner, AI (reprint author), NIDA,NIH,5600 FISHERS LANE,ROOM 10-05,ROCKVILLE,MD 20857, USA. NR 30 TC 572 Z9 635 U1 11 U2 104 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 3 PY 1997 VL 278 IS 5335 BP 45 EP 47 DI 10.1126/science.278.5335.45 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XZ124 UT WOS:A1997XZ12400029 PM 9311924 ER PT J AU Varmus, H Satcher, D AF Varmus, H Satcher, D TI Ethical complexities of conducting research in developing countries SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 CTR DIS CONTROL & PREVENT,ATLANTA,GA 30329. RP Varmus, H (reprint author), NIH,BETHESDA,MD 20892, USA. NR 6 TC 206 Z9 211 U1 1 U2 18 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 OCT 2 PY 1997 VL 337 IS 14 BP 1003 EP 1005 DI 10.1056/NEJM199710023371411 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA XY423 UT WOS:A1997XY42300011 PM 9309109 ER PT J AU Cornman, JM Achenbaum, WA Cassel, CK Cohen, GD Cole, TR Fahey, C Friedland, RB Harootyan, LK Hayflick, L Holstein, MB Moody, HR Wetle, TT Schutz, CA AF Cornman, JM Achenbaum, WA Cassel, CK Cohen, GD Cole, TR Fahey, C Friedland, RB Harootyan, LK Hayflick, L Holstein, MB Moody, HR Wetle, TT Schutz, CA TI Questions for societies with ''third age'' populations SO ACADEMIC MEDICINE LA English DT Article AB By 2030, the number of people aged 65 and over in the United States will total 70.2 million, 20% of the U.S. population, making the older population a major consumer of goods and services, The demands of this growing group are already affecting the medical professional, changing the mix of patients, conditions treated, and what the profession and society consider acceptable outcomes, Medical education will have to adjust to these new demands by training in the diagnosis and treatment of older persons, by equating successful management of chronic conditions with curing illnesses or fixing hurts, and by dealing with the inevitability of death. Also, however, medical education should train students to understand that the rapid aging of the papulation has the potential to affect almost every human and societal arrangement and every social and economic institution, raising a host of ethical, moral, scientific, social, and economic questions. The Gerontological Society of America (GSA) has convened an informal working group to explore the issues raised by the extension of human life expectancy. The multidisciplinary group, which has 13 members from academia and the GSA, held its first meeting in May 1997, when it laid out the issues to be discussed in future meetings. To help frame the discussions, the group adopted the concept of the ''Third Age,'' a time in the life course when for most people the basic work of parenting is done, when, under-current arrangements and definitions, people are not heavily relied on for production (that is, a time when people for different reasons leave paid, full-time jobs), and when few positive roles are recognized. The group's discussions will explore sets of interrelated questions raised by longer life expectancy and the larger number of older people. These questions can be considered in five general themes: the further extension of human life expectancy, research choices, societal vision and values, global aging, and economies and Third Age populations, These questions are raised in the paper, and in coming months the group will discuss their implications. C1 UNIV MICHIGAN,INST GERONTOL,ANN ARBOR,MI 48109. MT SINAI MED CTR,DEPT GERIATR,NEW YORK,NY 10029. GEORGE WASHINGTON UNIV,CTR AGING HLTH & HUMAN,WASHINGTON,DC. UNIV TEXAS,MED BRANCH,INST MED HUMANITIES,GALVESTON,TX 77550. CONSULTANTS PURPOSE,ARLINGTON,VA. FORDHAM UNIV,THIRD AGE CTR,NEW YORK,NY 10023. GERONTOL SOC AMER,NATL ACAD AGING,WASHINGTON,DC 20005. UNIV CALIF SAN FRANCISCO,DEPT ANAT,SAN FRANCISCO,CA 94143. PK RIDGE CTR STUDY HLTH FAITH & ETH,CHICAGO,IL. CUNY HUNTER COLL,BROOKDALE CTR AGING,NEW YORK,NY 10021. NIA,NIH,BETHESDA,MD 20892. RP Cornman, JM (reprint author), GERONTOL SOC AMER,EXTENS LIFE WORKING GRP,1275 K ST NW,SUITE 350,WASHINGTON,DC 20005, USA. NR 1 TC 10 Z9 10 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD OCT PY 1997 VL 72 IS 10 BP 856 EP 862 DI 10.1097/00001888-199710000-00008 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA YC074 UT WOS:A1997YC07400010 PM 9347707 ER PT J AU Hodes, RJ AF Hodes, RJ TI Meeting the challenges of an aging population SO ACADEMIC MEDICINE LA English DT Editorial Material RP Hodes, RJ (reprint author), NIA,NIH,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD OCT PY 1997 VL 72 IS 10 BP 892 EP 893 DI 10.1097/00001888-199710000-00013 PG 2 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA YC074 UT WOS:A1997YC07400018 PM 9347711 ER PT J AU Chang, HC Samaniego, F Nair, BC Buonaguro, L Ensoli, B AF Chang, HC Samaniego, F Nair, BC Buonaguro, L Ensoli, B TI HIV-1 Tat protein exits from cells via a leaderless secretory pathway and binds to extracellular matrix-associated heparan sulfate proteoglycans through its basic region SO AIDS LA English DT Article DE Tat; extracellular; release; heparin binding; proteoglycans; AIDS; Kaposi's sarcoma ID HUMAN-IMMUNODEFICIENCY-VIRUS; FIBROBLAST GROWTH-FACTOR; TRANS-ACTIVATOR GENE; LONG TERMINAL REPEAT; KAPOSIS-SARCOMA; FACTOR-I; T-CELLS; ENDOTHELIAL-CELLS; SIGNAL SEQUENCE; SPINDLE CELLS AB Objective: To analyze the mechanisms of release and the extracellular fate of the HIV-1 Tat protein and to determine the Tat domain binding to the extracellular matrix. Design and methods: Release of Tat was studied by pulse-chase experiments with Tat-transfected COS-1 cells in the presence or absence of different serum concentrations, temperatures and drugs inhibiting the classical secretion pathway or endo-exocytosis, such as brefeldin A and methylamine. The binding of extracellular Tat to heparan sulfate proteoglycans (HSPG) was determined by using trypsin, heparin or heparinase in pulse-chase experiments, by gel shift and competition assays with radiolabeled heparin, and by heparin-affinity chromatography. The mapping of the Tat binding site to heparin was defined by functional assays of rescue of Tat-defective HIV-1 proviruses. Results: Tat is released in the absence of cell death or permeability changes. Tat release is dependent upon the temperature and serum concentration, and it is not blocked by brefeldin A or methylamine. After release, a portion of the protein remains in a soluble form whereas the other binds to extracellular matrix (ECM)associated HSPG. The HSPG-bound Tat can be retrieved into a soluble form by heparin, heparinase or trypsin. Binding to heparin is competed out by heparin-binding factors such as basic fibroblast growth factor (bFGF), and it is mediated by the Tat basic region which forms a specific complex with heparin which blocks HIV-1 rescue by exogenous Tat and allows purification of a highly biologically active protein. Conclusions: These results demonstrate that Tat exits from intact cells throught a leaderless secretion pathway which shares several features with that of acid FGF or bFGF. The released Tat binds to HSPG through its basic region and this determines its storage into the ECM, as occurs for bFGF. C1 IST SUPER SANITA,VIROL LAB,I-00161 ROME,ITALY. NCI,TUMOR CELL BIOL LAB,NIH,BETHESDA,MD 20892. UNIV MARYLAND,INST BIOTECHNOL,GREENEBAUM CANC CTR,BALTIMORE,MD 21201. ADV BIOSCI LABS INC,KENSINGTON,MD. INST NAZL TUMORI,FDN G PASCALE,DIV VIRAL ONCOL,NAPLES,ITALY. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 64 TC 268 Z9 275 U1 1 U2 10 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD OCT PY 1997 VL 11 IS 12 BP 1421 EP 1431 DI 10.1097/00002030-199712000-00006 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA YA043 UT WOS:A1997YA04300006 PM 9342064 ER PT J AU Ayyavoo, V Nagashunmugam, T Boyer, J Mahalingam, S Fernandes, LS Le, P Lin, J Nguyen, C Chattargoon, M Goedert, JJ Friedman, H Weiner, DB AF Ayyavoo, V Nagashunmugam, T Boyer, J Mahalingam, S Fernandes, LS Le, P Lin, J Nguyen, C Chattargoon, M Goedert, JJ Friedman, H Weiner, DB TI Development of genetic vaccines for pathogenic genes: construction of attenuated vif DNA immunization cassettes SO AIDS LA English DT Article DE HIV vif genotype; cellular and humoral immune responses; vaccine; transcomplementation; natural pathogen ID IMMUNODEFICIENCY-VIRUS TYPE-1; IN-VIVO; IMMUNE-RESPONSES; T-LYMPHOCYTES; HIV-1 MUTANTS; HTLV-III/LAV; CELL-LINES; HUMAN-SERA; REPLICATION; PROTEIN AB Objective: To develop a putative immunization cassette using HIV-1 vif accessory gene derived from HIV-1 clinical specimens as a component of a DNA vaccine for HIV-1. Methods: vii genes were cloned from HIV-l-infected patients and the sequence variation present within the patients was analyzed. Prototypic genetic variants were selected and the ability of these clones to induce humoral and cellular immune responses was studied in animals. The selected protective genetic variants were biologically characterized through transcomplementation assays using primary cells infected with a vii-defective HIV-1 proviral clone. Results: Analysis of vii variants from different patients revealed that vii is highly conserved with the open reading frame remaining intact in vivo. It was shown that attenuated vii clones from HIV-l-infected subjects can effectively induce both humoral and cellular responses against Vif protein in mice. Evaluation of the cellular responses in vitro using human cellular targets infected with a clinical HIV-1 isolate showed that vif clones could induce cellular responses capable of destroying the virus. Conclusions: The vif variants developed in this study exhibited non-productive phenotypes, yet were capable of inducing specific immune responses against HIV-1. These constructs could be used as part of a DNA vaccine strategy for HIV-1. This vaccine adaptation strategy could be used for the development of immunogens for any pathogen resulting in cross-reactive immunity and attenuated gene pathogenesis. C1 UNIV PENN,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. UNIV PENN,DEPT MED,DIV INFECT DIS,PHILADELPHIA,PA 19104. NCI,LAB VIRAL EPIDEMIOL,FREDERICK,MD 21701. RI Weiner, David/H-8579-2014; OI Ayyavoo, Velpandi/0000-0002-9043-0885 NR 49 TC 6 Z9 6 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD OCT PY 1997 VL 11 IS 12 BP 1433 EP 1444 DI 10.1097/00002030-199712000-00007 PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA YA043 UT WOS:A1997YA04300007 PM 9342065 ER PT J AU Perlman, DC ElSadr, WM Heifets, LB Nelson, ET Matts, JP Chirgwin, K Salomon, N Telzak, EE Klein, O Kreiswirth, BN Musser, JM Hafner, R AF Perlman, DC ElSadr, WM Heifets, LB Nelson, ET Matts, JP Chirgwin, K Salomon, N Telzak, EE Klein, O Kreiswirth, BN Musser, JM Hafner, R TI Susceptibility to levofloxacin of Mycobacterium tuberculosis isolates from patients with HIV-related tuberculosis and characterization of a strain with levofloxacin monoresistance SO AIDS LA English DT Article; Proceedings Paper CT 35th Interscience Conference on Antimicrobial Chemotherapy CY SEP, 1995 CL SAN FRANCISCO, CA DE tuberculosis; levofloxacin; fluoroquinolones; drug resistance; Mycobacterium tuberculosis ID MULTIDRUG-RESISTANT TUBERCULOSIS; NEW-YORK-CITY; IN-VITRO; EPIDEMIOLOGY; OFLOXACIN; MUTATIONS; IDENTIFICATION; CIPROFLOXACIN; QUINOLONE; GYRA AB Objective: To characterize the susceptibility to levofloxacin of clinical isolates of Mycobacterium tuberculosis (MTB) obtained from patients with HIV-related tuberculosis and to characterize the molecular genetics of levofloxacin resistance. Design and methods: Isolates from culture-positive patients in a United States multicenter trial of HIV-related TB were tested for susceptibility to levofloxacin by minimum inhibitory concentration (MIG) determinations in Bactec 7H12 broth. Automated sequencing of the resistance determining region of gyrA was performed. Results: Of the 135 baseline MTB isolates tested, 134 (99%; 95% exact binomial confidence interval, 95.9-99.9%) were susceptible to levofloxacin with an MIC less than or equal to 1.0 mu g/ml. We identified a previously unrecognized mis-sense mutation occurring at codon 88 of gyrA in a levofloxacin mono-resistant MTB isolate obtained from a patient with AIDS who had received ofloxacin for 8 months prior to the diagnosis of tuberculosis. Conclusions: Clinical MTB isolates from HIV-infected patients were generally susceptible to levofloxacin. However, the identification of a clinical isolate with mono-resistance to levofloxacin highlights the need for circumspection in the use of fluoroquinolones in the setting of potential HIV-related tuberculosis and for monitoring of rates of resistance of MTB isolates to fluoroquinolones. C1 BETH ISRAEL MED CTR,NEW YORK,NY 10003. HARLEM HOSP MED CTR,NEW YORK,NY. NATL JEWISH CTR IMMUNOL & RESP DIS,DENVER,CO. UNIV MINNESOTA,SCH PUBL HLTH,MINNEAPOLIS,MN. SUNY HLTH SCI CTR,DIV INFECT DIS,BROOKLYN,NY 11203. BRONX LEBANON HOSP CTR,BRONX,NY 10456. ST VINCENTS HOSP,AIDS CTR,PUBL HLTH RES INST,NEW YORK,NY. PUBL HLTH RES INST,TUBERCULOSIS CTR,NEW YORK,NY. BAYLOR COLL MED,DEPT PATHOL,SECT MOL PATHOBIOL,HOUSTON,TX 77030. METHODIST HOSP,HOUSTON,TX 77030. NIAID,DIV AIDS,BETHESDA,MD 20892. RP Perlman, DC (reprint author), BETH ISRAEL MED CTR,1ST AVE 16TH ST,NEW YORK,NY 10003, USA. FU NIAID NIH HHS [U01 AI046370, AI-37004] NR 27 TC 43 Z9 46 U1 2 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD OCT PY 1997 VL 11 IS 12 BP 1473 EP 1478 DI 10.1097/00002030-199712000-00011 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA YA043 UT WOS:A1997YA04300011 PM 9342069 ER PT J AU Sangiorgi, G Kolodgie, FD Farb, A Ferrans, V Zhang, J Kwon, HM Edwards, WD Holmes, DR Virmani, R Schwartz, RS AF Sangiorgi, G Kolodgie, FD Farb, A Ferrans, V Zhang, J Kwon, HM Edwards, WD Holmes, DR Virmani, R Schwartz, RS TI Is apoptosis responsible for late neointimal regression following PTCA in humans? SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract C1 ARMED FORCES INST PATHOL,WASHINGTON,DC 20306. NATL INST HLTH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT PY 1997 VL 80 SI 7A BP TC220 EP TC220 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YC885 UT WOS:A1997YC88500217 ER PT J AU Harris, TB Savage, PJ Tell, GS Hann, M Kumanyika, S Lynch, JC AF Harris, TB Savage, PJ Tell, GS Hann, M Kumanyika, S Lynch, JC TI Carrying the burden of cardiovascular risk in old age: associations of weight and weight change with prevalent cardiovascular disease, risk factors, and health status in the Cardiovascular Health Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE weight; aging; cardiovascular disease; coronary artery disease; health status; obesity; Cardiovascular Health Study; humans; risk factors; elderly ID US ADULTS; BODY-WEIGHT; ATHEROSCLEROSIS; CHOLESTEROL; OVERWEIGHT; MORTALITY; OBESITY; PEOPLE; LEVEL; WOMEN AB Measured weight in old age, reported weight at age 50 y, and weight change from age 50 y to old age were studied in association with prevalent cardiovascular disease (CVD), CVD risk factors, acid health status in a population of 4954 men and women aged greater than or equal to 65 y in the Cardiovascular Health Study (CHS). Heavier weight (ie, generally weight in the fourth quartile for the cohort) at age 50 y was more closely associated with prevalent CVD than was current weight, with these associations stronger in women than in men. Heavier current weight and heavier weight at age 50 y were associated with cardiovascular risk factors, including higher blood pressure, lower high-density-lipoprotein cholesterol, and higher fasting insulin. Heavier weight at both time points was related to mobility problems in both men and women and to lower current physical activity levels; among women, strong associations were also seen with lower education and current income. Remaining within 10% of reported weight at age 50 y was associated with better health status as measured by reported health, mobility difficulty, number of medications, and prevalent CVD in men. Paradoxically, most cardiovascular risk factors were lowest for weight losers despite an association of weight loss with poorer health. In this cohort of persons aged greater than or equal to 65 y, heavier weight was associated with CVD and CVD risk factors, suggesting that prevention of overweight may prove beneficial in improving cardiovascular risk in older persons. Weight stability from age 50 y to old age was associated with better health status than was weight gain or loss. C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV BERGEN,DEPT PUBL HLTH & PRIMARY HLTH CARE,BERGEN,NORWAY. UNIV CALIF DAVIS,SCH MED,DEPT MED,DAVIS,CA. UNIV ILLINOIS,DEPT HUMAN NUTR & DIETET,CHICAGO,IL. UNIV NEBRASKA,MED CTR,LINCOLN,NE. RP Harris, TB (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,GATEWAY BLDG,ROOM 3C-309,7201 WISCONSIN AVE,BETHESDA,MD 20892, USA. RI Tell, Grethe/G-5639-2015 OI Tell, Grethe/0000-0003-1386-1638 FU NHLBI NIH HHS [N01-HC-87081, N01-HC-87079, N01-HC-87080] NR 28 TC 67 Z9 68 U1 1 U2 1 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 OCT PY 1997 VL 66 IS 4 BP 837 EP 844 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XY491 UT WOS:A1997XY49100014 PM 9322558 ER PT J AU Jacques, PF Felson, DT Tucker, KL Mahnken, B Wilson, PWF Rosenberg, IH Rush, D AF Jacques, PF Felson, DT Tucker, KL Mahnken, B Wilson, PWF Rosenberg, IH Rush, D TI Plasma 25-hydroxyvitamin D and its determinants in an elderly population sample SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE vitamin D; age; elderly individuals; 25-hydroxyvitamin D; Framingham Heart Study; sunlight exposure ID VITAMIN-D STATUS; CIRCULATING CONCENTRATIONS; SERUM 25-HYDROXYVITAMIN-D; NUTRITIONAL-STATUS; AGE; PEOPLE; SUNLIGHT; QUESTIONNAIRE; ULTRAVIOLET; PARAMETERS AB This study describes the distribution and determinants of plasma 25-hydroxyvitamin D [25(OH)D] concentrations and risk factors for low 25(OH)D (less than or equal to 37.5 nmol/L) in 290 men and 469 women aged 67-95 y who were in the Framingham Heart Study cohort. Mean (+/- SD) 25(OH)D concentrations were 82 +/- 29 nmol/L in men and 71 +/- 29 nmol/L in women. 25(OH)D was low in 6.2% of men and 14.5% of women. 25(OH)D concentrations were strongly associated with season of examination, inversely associated with time spent indoors and body mass index, and positively associated with dietary vitamin D intake. In women, concentrations were also inversely associated with age and positively associated with supplemental vitamin D intake and residence for greater than or equal to 3 mo/y in Florida, California, or Arizona, and in men were positively associated with serum creatinine concentrations. Similar amounts of variance in 25(OH)D concentrations were explained by vitamin D intake and sunlight exposure, the former being more important in women and the latter in men. None of the known or suspected determinants of vitamin D status could explain the lower 25(OH)D concentrations in women, but the sex difference was not seen for individuals examined during the winter. Results from this population-based sample of elderly individuals suggest that inadequate vitamin D status is an important public health problem, which could be readily addressed by adequate vitamin D intake or sunlight exposure. C1 BOSTON MED CTR,ARTHRIT CTR,BOSTON,MA. NHLBI,FRAMINGHAM HEART STUDY,NIH,FRAMINGHAM,MA. RP Jacques, PF (reprint author), TUFTS UNIV,USDA,JEAN MAYER HUMAN NUTR RES CTR AGING,711 WASHINGTON ST,BOSTON,MA 02111, USA. RI Tucker, Katherine/A-4545-2010; OI Tucker, Katherine/0000-0001-7640-662X FU NHLBI NIH HHS [N01-HC-38038, R01-HL-40423-05]; NINDS NIH HHS [2-R01-NS-17950-12] NR 42 TC 180 Z9 184 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 OCT PY 1997 VL 66 IS 4 BP 929 EP 936 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XY491 UT WOS:A1997XY49100026 PM 9322570 ER PT J AU Vogel, S Contois, JH Tucker, KL Wilson, PWF Schaefer, EJ LammiKeefe, CJ AF Vogel, S Contois, JH Tucker, KL Wilson, PWF Schaefer, EJ LammiKeefe, CJ TI Plasma retinol and plasma and lipoprotein tocopherol and carotenoid concentrations in healthy elderly participants of the Framingham Heart Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE tocopherol; vitamin A; carotenoids; retinol; plasma; lipoproteins; elderly; Framingham Heart Study ID FOOD FREQUENCY QUESTIONNAIRE; ALPHA-TOCOPHEROL; BETA-CAROTENE; VITAMIN-E; BIOCHEMICAL INDICATORS; DIETARY QUESTIONNAIRE; DENSITY-LIPOPROTEINS; GAMMA-TOCOPHEROL; SERUM; WOMEN AB Data on plasma concentrations of tocopherols and the major carotenoids in adults aged greater than or equal to 65 y, particularly in those > 80 y, are sparse. In the current study retinol, tocopherol (alpha- and gamma-tocopherols), and carotenoid (lutein/zeaxanthin, cryptoxanthins, lycopene, and alpha- and beta-carotene) concentrations were determined in 638 subjects, 230 men (aged 75 +/- 5 y) and 408 women (76 +/- 6 y), of the Framingham Heart Study. All subjects were free of clinical evidence of cardiovascular disease and cancer. Percentile ranges were comparable with those established in younger cohorts. Moreover, women had significantly higher plasma cu-tocopherol and plasma and lipoprotein concentrations of beta-cryptoxanthin and alpha- and beta-carotene than did men. Lycopene concentrations were inversely correlated with age and lowest among subjects greater than or equal to 80 y. Total intakes (diet + supplements) of vitamin C and vitamin E, but not dietary intakes alone, were positively associated with plasma cr-tocopherol and inversely associated with gamma-tocopherol concentrations. In multivariate analyses, plasma cholesterol and triacylglycerol concentrations and total intake of vitamins E and C predicted 64% and 55% of the plasma alpha-tocopherol concentrations in men and women, respectively. Important predictors for the majority of carotenoids included plasma cholesterol concentration, body mass index (negative effect), and smoking status (negative effect); for lycopene concentration they included cholesterol concentration and age (negative effect). In summary, percentile ranges and lipoprotein distributions were comparable with those established in younger cohorts, suggesting that overall antioxidant status is not altered in people between the ages of 67 and 96 y. C1 UNIV CONNECTICUT,DEPT NUTR SCI,STORRS,CT 06269. TUFTS UNIV,USDA,JEAN MAYER DEPT AGR HUMAN NUTR RES CTR,PROGRAM EPIDEMIOL,BOSTON,MA 02111. TUFTS UNIV,USDA,JEAN MAYER DEPT AGR HUMAN NUTR RES CTR,LIPID METAB LAB,BOSTON,MA 02111. NHLBI,FRAMINGHAM HEART STUDY,FRAMINGHAM,MA. RI Tucker, Katherine/A-4545-2010; OI Tucker, Katherine/0000-0001-7640-662X NR 40 TC 80 Z9 80 U1 0 U2 1 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 OCT PY 1997 VL 66 IS 4 BP 950 EP 958 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XY491 UT WOS:A1997XY49100029 PM 9322573 ER PT J AU Ernst, ND Sempos, CT Briefel, RR Clark, MB AF Ernst, ND Sempos, CT Briefel, RR Clark, MB TI Consistency between US dietary fat intake and serum total cholesterol concentrations: the National Health and Nutrition Examination Surveys SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Fats and Oil Consumption in Health and Disease - Current Concepts and Controversies CY APR 24-25, 1995 CL ROCKEFELLER UNIV, NEW YORK, NY SP New York Hosp, Cornell Univ Med Coll, Rockefeller Univ, Harvard Med Sch, New York Acad Med, Reg Nutr Ctr, Strang Canc Prevent Ctr HO ROCKEFELLER UNIV DE dietary fat; serum cholesterol; national nutrition surveys; NHANES; National Health and Nutrition Examination Survey ID DENSITY-LIPOPROTEIN CHOLESTEROL; EDUCATION-PROGRAM AB The National Health and Nutrition Examination Surveys (NHANESs) are conducted periodically to assess the health and nutritional status of the US population by means of standardized interviews and physical examinations. Since the early 1970s there have been three national cross-sectional surveys: NHANES I, 1971-1974; NHANES II, 1976-1980; and NHANES LII, phase I, 1988-1991. During the 18 y between the midpoint of NHANES I (1972) and the midpoint of phase 1 of NHANES III (1990), the age-adjusted mean percentage of energy from fat declined from 36.4% to 34.1% for adults aged 20-74 y. Trend data are shown for dietary fat and cholesterol as well as for serum cholesterol from NHANES I (1971-1975) to NHANES III (1988-1991) by age, sex, and race-ethnicity. The results document a decline in dietary fat, saturated fat, dietary cholesterol, and serum cholesterol. The observed changes reflect those that are predicted by the classic Keys and Hegsted formulas. Changes in reported intake ate matched by similar shifts in the food supply for sources of these nutrients. These changes suggest that the Healthy People 2000 goal of reducing the mean serum cholesterol concentration of US adults to less than or equal to 200 mg/dL (5.17 mmol/L) is attainable. The changes in diet are promising, yet we are challenged to achieve greater reductions in the intake of total fat and saturated fatty acids. C1 CTR DIS CONTROL & PREVENT, NATL CTR HLTH STAT, HYATTSVILLE, MD 20782 USA. RP Ernst, ND (reprint author), NHLBI, ROCKLEDGE CTR 2,NIH,6701 ROCKLEDGE DR, ROCKLEDGE BLDG, ROOM 8112, BETHESDA, MD 20892 USA. NR 37 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 1997 VL 66 SU 4 BP 965 EP 972 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XY890 UT WOS:A1997XY89000004 ER PT J AU Rivlin Dannenberg Trichopoulou Breslow Ernst AF Rivlin Dannenberg Trichopoulou Breslow Ernst TI Overview lectures: discussion SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Editorial Material C1 CORNELL UNIV, MED CTR, NEW YORK HOSP, STRANG CORNELL CANC PREVENT CTR, NEW YORK, NY 10021 USA. CORNELL UNIV, COLL MED, NEW YORK, NY 10021 USA. ROCKEFELLER UNIV, BIOCHEM GENET & METAB LAB, NEW YORK, NY 10021 USA. NHLBI, NIH, BETHESDA, MD 20892 USA. NATL SCH PUBL HLTH, DEPT NUTR & BIOCHEM, GR-12521 ATHENS, GREECE. RP Rivlin (reprint author), MEM SLOAN KETTERING CANC CTR, DEPT MED, GI NUTR SERV, CLIN NUTR RES UNIT, 1275 YORK AVE, NEW YORK, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 1997 VL 66 SU 4 BP 973 EP 973 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XY890 UT WOS:A1997XY89000005 ER PT J AU Meltzer, AA Everhart, JE AF Meltzer, AA Everhart, JE TI Association between diabetes and elevated serum alanine aminotransferase activity among Mexican Americans SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE alanine aminotransferase; alcohol drinking; body mass index; confounding factors (epidemiology); diabetes mellitus; health surveys; risk factors ID GAMMA-GLUTAMYL-TRANSFERASE; LIVER-FUNCTION TESTS; C VIRUS-INFECTION; BLOOD-DONORS; HEPATITIS-C; ALCOHOL-CONSUMPTION; HIGH PREVALENCE; MORBID-OBESITY; RISK-FACTORS; FOLLOW-UP AB Elevated activities of serum aminotransferases are a common sign of liver disease and are observed more frequently among diabetics than in the general population. Whether this association is due to confounding factors is unknown. The authors investigated whether diabetes was significantly associated with elevated serum activity of alanine aminotransferase (ALT) after adjustment for factors common to both diabetes and raised ALT, Data from 2,999 men and women aged 20-74 years representative of the Mexican American population of the southwestern United States were obtained from the Hispanic Health and Nutrition Examination Survey (1982-1984). Approximately 6% of men and 2% of women had elevated serum ALT activity (>43 IU/liter), The odds ratio for diabetes as a predictor of elevated ALT was 4.1 (95% confidence interval 2.3-7.6) adjusted for age and sex, which decreased to 3.0 (95% confidence interval 0.92-9.74) after adjustment for age, sex, body mass index, alcohol consumption, and other factors. In addition to diabetes, body mass index was also significantly (p < 0.05) associated with elevated ALT activity. Heavier alcohol consumption and male sex increased the likelihood of elevated ALT, whereas coffee consumption reduced it. Diabetes and liver injury appear to be associated, even with control for factors in common. C1 NIDDKD,EPIDEMIOL & CLIN TRIALS BRANCH,DIV DIGEST DIS & NUTR,BETHESDA,MD 20892. SOCIAL & SCI SYST INC,BETHESDA,MD. FU NIDDK NIH HHS [N01-DK-1-2282] NR 62 TC 42 Z9 43 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 OCT 1 PY 1997 VL 146 IS 7 BP 565 EP 571 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XZ752 UT WOS:A1997XZ75200005 PM 9326434 ER PT J AU Lima, AAM Silva, TMJ Gifoni, AMR Barrett, LJ McAuliffe, IT Bao, Y Fox, JW Fedorko, DP Guerrant, RL AF Lima, AAM Silva, TMJ Gifoni, AMR Barrett, LJ McAuliffe, IT Bao, Y Fox, JW Fedorko, DP Guerrant, RL TI Mucosal injury and disruption of intestinal barrier function in HIV-Infected individuals with and without diarrhea and cryptosporidiosis in northeast Brazil SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANION-EXCHANGE CHROMATOGRAPHY; CELIAC-DISEASE; FECAL LACTOFERRIN; CROHNS-DISEASE; SYNDROME AIDS; PERMEABILITY; ENTEROPATHY; BACTERIAL; MALABSORPTION AB Objectives: To determine the relative effects of AIDS-related diarrhea with or without cryptosporidiosis and microsporidiosis on intestinal function and injury. Methods: We studied 40 HIV-infected patients (20 with and 20 without diarrhea) and 13 healthy volunteers, using the differential urinary excretion of ingested lactulose and mannitol as respective markers of barrier disruption and overall villous surface area. We also examined them for fecal leukocytes, lactoferrin, and alpha(1)-antitrypsin. Fasting subjects drank test solution containing lactulose (5 g) and mannitol (1 g). Urine was collected for 5 h and tested for sugars by high-performance liquid chromatography with pulsed amperometric detection. Results: HIV-positive patients with diarrhea had a 2.8-fold higher lactulose:mannitol excretion ratio (L:M) than HIV-positive patients without diarrhea (p = 0.01) and 10.4-fold higher than healthy volunteers (p = 0.004). This was accounted for by a 1.5- to 3.1-fold higher rate of lactulose excretion by HIV patients with diarrhea than by those without diarrhea or by healthy volunteers. Mannitol excretion was 32-55% less in patients with diarrhea than in those without diarrhea or in healthy volunteers. Patients with cryptosporidial diarrhea had a nearly 6-fold higher L:M ratio than those without diarrhea (p < 0.001) and nearly 3-fold higher than those with non-cryptosporidial diarrhea (p = 0.02). One patient with microsporidial infection had a nearly 3-fold higher L:M ratio than controls without diarrhea. alpha(1)-Antitrypsin was positive in 40% of HIV-positive patients with cryptosporidial infections and none of 12 HIV-positive patients with non-cryptosporidial diarrhea. Fecal lactoferrin or leukocytes were increased in all HIV patients with diarrhea. Conclusion: HIV infection is associated with intestinal dysfunction and injury, even in patients who do not have diarrhea. However, those with diarrhea, especially with cryptosporidiosis or microsporidiosis, have even greater disruption of intestinal barrier function with potentially important nutritional consequences. C1 UNIV HOSP,CLIN RES UNIT,FORTALEZA,CEARA,BRAZIL. STATE SECRETARY HLTH CE,HOSP SAO JOSE DE DOENCAS,FORTALEZA,CEARA,BRAZIL. UNIV VIRGINIA,SCH MED,DIV GEOG & INT MED,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,SCH MED,DEPT MICROBIOL,BIOMOL RES FACIL,CHARLOTTESVILLE,VA 22908. NIH,WARREN G MAGNUSON CLIN CTR,MICROBIOL SERV,DEPT CLIN PATHOL,BETHESDA,MD 20892. RP Lima, AAM (reprint author), FED UNIV CEARA,CLIN RES UNIT,DEPT PHYSIOL & PHARMACOL,POB 3229,BR-60436160 FORTALEZA,CEARA,BRAZIL. FU NIAID NIH HHS [P01-AI-26512] NR 46 TC 37 Z9 42 U1 0 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 1997 VL 92 IS 10 BP 1861 EP 1866 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XZ848 UT WOS:A1997XZ84800021 PM 9382053 ER PT J AU Goetsch, R Minor, JR Piscitelli, SC AF Goetsch, R Minor, JR Piscitelli, SC TI Home collection and non-blood-based methods of testing for the human immunodeficiency virus SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article ID HIV ANTIBODY; SALIVA; TIME; AIDS C1 NIH,CLIN PHARMACOKINET RES LAB,DEPT PHARM,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892. US FDA,DIV PHARMACOVIGILANCE & EPIDEMIOL,ROCKVILLE,MD 20857. IDAHO STATE UNIV,POCATELLO,ID 83209. GLAXO WELLCOME INC,US MED AFFAIRS,STRATEG INFORMAT DEPT,RES TRIANGLE PK,NC 27709. NIAID,BETHESDA,MD 20892. NR 19 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD OCT 1 PY 1997 VL 54 IS 19 BP 2232 EP 2235 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YC512 UT WOS:A1997YC51200019 PM 9331447 ER PT J AU Agarwal, SK Debelenko, LV Kester, MB Guru, SC Manickam, P Olufemi, SE Skarulis, MC Heppner, C Crabtree, JS Lubensky, IA Zhuang, Z Kim, YS Saggar, SK Chandrasekharappa, SC Collins, FS Liotta, LA Spiegel, AM Burns, AL Emmert-Buck, MR Marx, SJ AF Agarwal, SK Debelenko, LV Kester, MB Guru, SC Manickam, P Olufemi, SE Skarulis, MC Heppner, C Crabtree, JS Lubensky, IA Zhuang, Z Kim, YS Saggar, SK Chandrasekharappa, SC Collins, FS Liotta, LA Spiegel, AM Burns, AL Emmert-Buck, MR Marx, SJ TI Analysis of identical germline mutations in the MEN1 gene encountered repeatedly in unrelated families. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. NCI, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 315 BP A59 EP A59 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000314 ER PT J AU Allikmets, R Shroyer, NF Singh, N Seddon, JM Lewis, RA Bernstein, P Peiffer, A Zabriskie, N Li, Y Hutchinson, A Dean, M Lupski, JR Leppert, M AF Allikmets, R Shroyer, NF Singh, N Seddon, JM Lewis, RA Bernstein, P Peiffer, A Zabriskie, N Li, Y Hutchinson, A Dean, M Lupski, JR Leppert, M TI The Stargardt disease gene (ABCR) is mutated in age-related macular degeneration. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. SAIC Frederick, Frederick, MD USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Utah, Moran Eye Ctr, Salt Lake City, UT 84112 USA. Univ Utah, Eccles Inst Human Genet, Salt Lake City, UT 84112 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 6 BP A3 EP A3 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000007 ER PT J AU Almqvist, E Chong, SS Nichol, K Telenius, H La Tray, L Bourdelat-Parks, B Haddad, BR Squitieri, F Anvret, M Van den Engh, G Hayden, M AF Almqvist, E Chong, SS Nichol, K Telenius, H La Tray, L Bourdelat-Parks, B Haddad, BR Squitieri, F Anvret, M Van den Engh, G Hayden, M TI Different mutation rates of similar sized CAG tracts of affected Huntington disease chromosomes by single sperm analysis SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. NIH, Natl Ctr Human Genome Res, Bethesda, MD 20892 USA. Univ Washington, Dept Mol Biotechnol, Seattle, WA 98195 USA. INM IRCCS Neuromed, Naples, Italy. Univ Naples Federico II, Dept Neurol Sci, Naples, Italy. Karolinska Inst, S-10401 Stockholm, Sweden. RI Hayden, Michael/D-8581-2011 OI Hayden, Michael/0000-0001-5159-1419 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1768 BP A303 EP A303 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001772 ER PT J AU Amar, MJA Knapper, CL Maeda, N Paigen, B Santamarina-Fojo, S Brewer, HB AF Amar, MJA Knapper, CL Maeda, N Paigen, B Santamarina-Fojo, S Brewer, HB TI Gene therapy for atherosclerosis secondary to genetic dyslipoproteinemias by overexpression of hepatic lipase and apolipoprotein A-I. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Jackson Lab, Bar Harbor, ME 04609 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2072 BP A354 EP A354 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002074 ER PT J AU Anikster, Y Gropman, A Lewanda, AF Tifft, C Schonberg, S Krasnewich, D AF Anikster, Y Gropman, A Lewanda, AF Tifft, C Schonberg, S Krasnewich, D TI Partial trisomy 10p from maternal pericentric inversion with severe neurologic sequelae. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Amer Med Lab, Fairfax, VA USA. Ctr Med Genet, Rockville, MD USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD USA. NIMH, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 500 BP A90 EP A90 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000500 ER PT J AU Badner, JA Gershon, ES Goldin, LR AF Badner, JA Gershon, ES Goldin, LR TI Best families for analyzing linkage in complex traits: Smaller may be better. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1118 BP A194 EP A194 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001122 ER PT J AU Bailey-Wilson, JE Wyszynski, DF Middelton, LA AF Bailey-Wilson, JE Wyszynski, DF Middelton, LA TI Strategies to minimize coercion and conflict of interest when one of the principal investigators of a genetic research study is also a study participant. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1257 BP A217 EP A217 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001260 ER PT J AU Barlow, C Liyanage, M Brown, K Moens, P Deng, CX Tagle, D Ried, T Wynshaw-Boris, A AF Barlow, C Liyanage, M Brown, K Moens, P Deng, CX Tagle, D Ried, T Wynshaw-Boris, A TI Understanding the pleiotropic effects of Atm by modeling in the mouse. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. NHGRI, NIH, Bethesda, MD USA. York Univ, Toronto, ON M3J 2R7, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 246 BP A47 EP A47 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000248 ER PT J AU Beaty, TH Ardenghi, E Banares, V Van der Ende, J Garcia-Delgado, C Vinageras-Guarneros, E Wyszynski, DF AF Beaty, TH Ardenghi, E Banares, V Van der Ende, J Garcia-Delgado, C Vinageras-Guarneros, E Wyszynski, DF TI Genetics analysis of multiplex non-syndromic cleft lip with or without cleft palate: Results from 8 collaborative centers. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Ctr Nacl Genet Med, Buenos Aires, DF, Argentina. Hosp Ninos Sor Maria Ludovica, La Plata, Argentina. Johns Hopkins Univ, Baltimore, MD 21218 USA. Univ Nijmegen Hosp, NL-6500 HB Nijmegen, Netherlands. Hosp Infantil Mexico Federico Gomez, Mexico City, DF, Mexico. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1555 BP A267 EP A267 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001558 ER PT J AU Becker, KG Simon, RM Biddison, WE Bailey-Wilson, JE McFarland, HF Trent, JM AF Becker, KG Simon, RM Biddison, WE Bailey-Wilson, JE McFarland, HF Trent, JM TI Clustering of non-MHC susceptibility candidate loci in human autoimmune diseases. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Canc Genet Lab, Bethesda, MD 20892 USA. NINDS, Neuroimmunol Branch, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, Bethesda, MD 20892 USA. NHGRI, Sect Stat Genet, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1557 BP A267 EP A267 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001559 ER PT J AU Bell, KA Van Deerlin, PG du Manoir, S Feinberg, RF Haddad, BR AF Bell, KA Van Deerlin, PG du Manoir, S Feinberg, RF Haddad, BR TI Diagnosis of aneuploidy in archival formalin-fixed paraffin-embedded pregnancy loss tissues by comparative genomic hybridization. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. NHGR, NIH, Bethesda, MD USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 834 BP A146 EP A146 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000834 ER PT J AU Bellus, GA Baker, A Spector, EB Hunter, AGW Hecht, J Lewanda, AF Szabo, J Francomano, CA AF Bellus, GA Baker, A Spector, EB Hunter, AGW Hecht, J Lewanda, AF Szabo, J Francomano, CA TI Mutational analysis of FGFR3 in thanatophoric dysplasia, type I. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Childrens Hosp Eastern Ontario, Ottawa, ON K1H 8L1, Canada. Univ Texas, Houston, TX USA. Ctr Med Genet, Rockville, MD USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1908 BP A326 EP A326 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001911 ER PT J AU Bendahhou, E Vandenbergh, DJ Pugh, E Rodriguez, LA Miller, I Lachman, H Uhl, GR AF Bendahhou, E Vandenbergh, DJ Pugh, E Rodriguez, LA Miller, I Lachman, H Uhl, GR TI Dopaminergic gene alleles in polysubstance abusers and controls: Effects of COMT and DRD4 allelic status are at lease additive. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, NIDA, IRP,Mol Neurobiol Branch, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. NIH, Nat Human Genome Res Inst, Baltimore, MD 21224 USA. Albert Einstein Coll Med, Dept Psychiat, Bronx, NY 10461 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1776 BP A304 EP A304 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001779 ER PT J AU Bergen, AW Kokoszka, J Peterson, R Long, JC Linnoila, M Goldman, D AF Bergen, AW Kokoszka, J Peterson, R Long, JC Linnoila, M Goldman, D TI mu opioid receptor (OPRM1) variants: lack of association with alcohol and drug dependence. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. NIAAA, Clin Studies Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2328 BP A398 EP A398 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002332 ER PT J AU Brown, S Zhou, J Shanen, D Yu, CY Kozak, C Warburton, D AF Brown, S Zhou, J Shanen, D Yu, CY Kozak, C Warburton, D TI Holoprosencephaly and thumb hypoplasia in the 13q-syndrome map to a I Mb region in 13q32 with conserved synteny to distal MMU14 and containing ZIC2, a human homologue of mouse Zic2 and Drosophila odd-paired. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Columbia Univ, Dept Ob Gyn, New York, NY 10027 USA. Columbia Univ, Dept Genet & Dev, New York, NY 10027 USA. Presbyterian Hosp, New York, NY USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1778 BP A304 EP A304 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001780 ER PT J AU Buchanan, PB Laundon, CH Ning, Y Donlon, T AF Buchanan, PB Laundon, CH Ning, Y Donlon, T TI Prenatal detection of a deletion in the 15 (q11.1q13) Prader Willi Syndrome Angelman Syndrome region. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 GeneCare Med Genet Ctr, Chapel Hill, NC USA. NHGRI, Bethesda, MD USA. Univ Hawaii, Kapiolani Med Ctr, Honolulu, HI 96822 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2206 BP A377 EP A377 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002207 ER PT J AU Burgess, CE Lindblad, K Sideransky, E Ginns, E Yuan, Q Lee, P Rapoport, JL Schalling, M AF Burgess, CE Lindblad, K Sideransky, E Ginns, E Yuan, Q Lee, P Rapoport, JL Schalling, M TI CAG expansions and childhood-onset schizophrenia SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Karolinska Inst, Neurogenet Unit, S-10401 Stockholm, Sweden. NIMH, Bethesda, MD 20892 USA. RI Schalling, Martin/F-1518-2015 OI Schalling, Martin/0000-0001-5011-2922 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1780 BP A305 EP A305 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001784 ER PT J AU Bussey, KJ Lawce, HJ Olson, SB Shu, XO Arthur, DC Heifetz, S Womer, R Giller, R Krailo, M Magenis, RE AF Bussey, KJ Lawce, HJ Olson, SB Shu, XO Arthur, DC Heifetz, S Womer, R Giller, R Krailo, M Magenis, RE TI Loss of 1p36 in malignant pediatric germ cell tumors. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. Univ Minnesota, Minneapolis, MN 55455 USA. NCI, Bethesda, MD 20892 USA. Indiana Univ, Indianapolis, IN 46204 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Denver Childrens Hosp, Denver, CO USA. Childrens Canc Grp, Arcadia, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 330 BP A62 EP A62 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000333 ER PT J AU Chamberlin, ME Ubagai, T Mudd, SH Pao, VY Nguyen, TK Greene, CL Thomas, JA Freehauf, C Chou, JY AF Chamberlin, ME Ubagai, T Mudd, SH Pao, VY Nguyen, TK Greene, CL Thomas, JA Freehauf, C Chou, JY TI Novel mutations in the methionine adenosyltransferase 1A gene that cause isolated persistent hypermethioninemia. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. NIMH, Lab Gen & Comparat Biochem, NIH, Bethesda, MD 20892 USA. Childrens Hosp, Denver, CO 80218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1448 BP A249 EP A249 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001451 ER PT J AU Charnas, LR Hopkins, E Marini, JC AF Charnas, LR Hopkins, E Marini, JC TI The dynamic deformation sequence of basilar invagination in osteogenesis imperfecta. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, Sect Connect Tissue Disorders, HDB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 519 BP A93 EP A93 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000521 ER PT J AU Chen, S Wang, QL Nie, Z Copeland, NG Jenkins, NA Lennon, G Zack, DJ AF Chen, S Wang, QL Nie, Z Copeland, NG Jenkins, NA Lennon, G Zack, DJ TI Cloning and characterization of RHDP3, a novel photoreceptor-specific Otx-like homeodomain protein that binds to and transactivates the rhodopsin promoter. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21287 USA. NCI, Frederick Canc Res & Dev Ctr, Mammalian Genet Lab, ABL, Frederick, MD 21702 USA. Univ Calif Lawrence Livermore Natl Lab, Livermore, CA 94550 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 36 BP A9 EP A9 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000036 ER PT J AU Chen, X Hamon, M Centola, M Rotter, JI Fischel-Ghodsian, N AF Chen, X Hamon, M Centola, M Rotter, JI Fischel-Ghodsian, N CA FMF Int Consortium TI Exclusion of FMFc7, a putative C2H2 type zinc finger protein as a candidate gene for Familial Mediterranean fever (FMF). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Cedars Sinai Med Ctr, Dept Pediat & Med Genet, Los Angeles, CA 90048 USA. NIAMSD, Arthritis & Rheumalism Branch, NIH, Bethesda, MD 20892 USA. RI Hamon, Melanie/B-3501-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2224 BP A380 EP A380 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002227 ER PT J AU Chen, Z Notohamiprodjo, M Guan, XY Blackwell, S Stout, K Turner, A Richkind, K Trent, JM Lamb, A Sandberg, AA AF Chen, Z Notohamiprodjo, M Guan, XY Blackwell, S Stout, K Turner, A Richkind, K Trent, JM Lamb, A Sandberg, AA TI Amplification of 9p in the pathogenesis of polycythemia vera. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Genzyme Genet, Santa Fe, NM USA. Natl Ctr Human Genome Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 680 BP A120 EP A120 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000682 ER PT J AU Ciotti, M Marrone, A Owens, IS AF Ciotti, M Marrone, A Owens, IS TI Genetic polymorphism in the human UGT1A6 UDP-glucuronosyltransferase: Pharmacological implications. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, Heritable Disorders Branch, NIH, Bethesda, MD USA. NIDDK, Digest Dis Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1449 BP A249 EP A249 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001449 ER PT J AU Cooney, KA Lange, E Wyszynski, DF Smith, JR Carpten, JD Trent, JM Bailey-Wilson, JE AF Cooney, KA Lange, E Wyszynski, DF Smith, JR Carpten, JD Trent, JM Bailey-Wilson, JE TI Linkage analysis in African-American prostate cancer families using 1q24-25 markers. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. NHGRI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1582 BP A272 EP A272 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001584 ER PT J AU Dawson, PA Grassi, G Marini, JC AF Dawson, PA Grassi, G Marini, JC TI Suppression of mutant type I collagen mRNA by hammerhead ribozymes in cultured skin fibroblasts. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, Connect Tissue Disorders Heritable Disorders Bran, NIH, Bethesda, MD USA. RI Dawson, Paul/B-1268-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2076 BP A354 EP A354 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002076 ER PT J AU Dean, M Stephens, JC Shin, HD Huttley, GA Gerrard, B Malasky, M Smith, MW O'Brien, SJ Carrington, M AF Dean, M Stephens, JC Shin, HD Huttley, GA Gerrard, B Malasky, M Smith, MW O'Brien, SJ Carrington, M TI Mutational and population genetic analysis of the chemokine receptor 5 (CCR5) gene. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Lab Genom Divers, Frederick, MD 21701 USA. NCI, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21701 USA. RI Smith, Michael/B-5341-2012; Huttley, Gavin/G-5169-2015 OI Huttley, Gavin/0000-0001-7224-2074 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 231 BP A44 EP A44 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000232 ER PT J AU Deng, Z Aksentijevich, I Balow, JE Blake, T Centola, M Chen, X Collins, FS Doggett, N Fischel-Ghodsian, N Gumucio, D Liu, P Pras, E Pras, M Richards, N Richards, RI Ricke, DO Rotter, JI Shohat, M Sood, R Wood, G Yokoyama, Y Zaks, N Kastner, DL AF Deng, Z Aksentijevich, I Balow, JE Blake, T Centola, M Chen, X Collins, FS Doggett, N Fischel-Ghodsian, N Gumucio, D Liu, P Pras, E Pras, M Richards, N Richards, RI Ricke, DO Rotter, JI Shohat, M Sood, R Wood, G Yokoyama, Y Zaks, N Kastner, DL TI Identification of FMF positional candidate genes within a 115-kb interval defined by historical recombinants. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAMS, ARB, NIH, Bethesda, MD USA. NHGRI, LGT, NIH, Bethesda, MD USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Calif Los Alamos Natl Lab, Los Alamos, NM USA. Univ Michigan, Ann Arbor, MI 48109 USA. Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. Womens & Childrens Hosp, Adelaide, SA, Australia. Beilinson Med Ctr, IL-49100 Petah Tiqwa, Israel. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1356 BP A234 EP A234 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001358 ER PT J AU Diehl, SR Erickson, RP AF Diehl, SR Erickson, RP TI Genome scan for teratogen-induced clefting susceptibility loci in the mouse. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Arizona, Hlth Sci Ctr, Dept Pediat, Tucson, AZ 85721 USA. NIDR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 168 BP A33 EP A33 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000168 ER PT J AU Fanos, JH Gatti, RA Lederman, HM Tagle, DA Winkelstein, JA AF Fanos, JH Gatti, RA Lederman, HM Tagle, DA Winkelstein, JA TI Beliefs ef carrier status by parents and siblings of individuals with ataxia-telangiectasia. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Natl Human Genome Res Inst, NIH, Bethesda, MD USA. Calif Pacific Med Ctr, San Francisco, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1272 BP A220 EP A220 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001274 ER PT J AU Feng, J Sobell, JL Heston, LL Goldman, D Cook, E Gelernter, J Kranzler, HR Sommer, SS AF Feng, J Sobell, JL Heston, LL Goldman, D Cook, E Gelernter, J Kranzler, HR Sommer, SS TI Mutation screening of candidate genes in psychiatric patients SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 City Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Genet, Duarte, CA 91010 USA. City Hope Natl Med Ctr, Beckman Res Inst, Div Mol Med, Duarte, CA 91010 USA. Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. NIAAA, Neurogenet Lab, Bethesda, MD USA. Univ Chicago, Dept Child Psychiat, Chicago, IL 60637 USA. Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1948 BP A333 EP A333 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001951 ER PT J AU Forlino, A Porter, FD Marini, JC AF Forlino, A Porter, FD Marini, JC TI Cre-mediated site-specific recombination in the murine COL1A1 gene: Generation of a conditional murine model for osteogenesis imperfecta. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, HDB, NIH, Bethesda, MD USA. RI Forlino, Antonella/H-5385-2015 OI Forlino, Antonella/0000-0002-6385-1182 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1456 BP A250 EP A250 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001458 ER PT J AU Forozan, F Veldman, R Parsa, NZ Barlund, M Tirkkonen, M Ethier, S Taetle, R Anzick, S Meltzer, PS Kallioniemi, A Kallioniemi, OP AF Forozan, F Veldman, R Parsa, NZ Barlund, M Tirkkonen, M Ethier, S Taetle, R Anzick, S Meltzer, PS Kallioniemi, A Kallioniemi, OP TI Application of cell lines for identification of genes implicated in breast cancer. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Canc Genet Lab, NIH, Bethesda, MD USA. Univ Tampere, FIN-33101 Tampere, Finland. Univ Michigan, Ann Arbor, MI 48109 USA. Arizona Canc Ctr, Tucson, AZ USA. RI Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 350 BP A65 EP A65 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000352 ER PT J AU Francomano, CA Szabo, JK Bellus, G Mack, M Baron, J Leschek, E Plotnick, L McIntosh, I Wilkin, DJ AF Francomano, CA Szabo, JK Bellus, G Mack, M Baron, J Leschek, E Plotnick, L McIntosh, I Wilkin, DJ TI A splice site alteration in the fibroblast growth factor receptor 3 (FGFR3) gene is associated with proportionate non-syndromic short stature. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD USA. NICHD, NIH, Bethesda, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1951 BP A333 EP A333 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001950 ER PT J AU Gahl, W Brantly, M Hazelwood, S Kaiser-Kupfer, MI Iwata, F Bernardini, I AF Gahl, W Brantly, M Hazelwood, S Kaiser-Kupfer, MI Iwata, F Bernardini, I TI Clinical and laboratory findings in Hermansky-Pudlak Syndrome (HPS) patients homozygous for a 16-bp duplication in the HPS gene and patients not carrying this mutation. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, Sect Human Biochem Genet, HDB, Bethesda, MD 20892 USA. NHLBI, Crit Care Med Branch, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. NEI, Ophthalm Genet & Clin Serv Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1458 BP A251 EP A251 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001462 ER PT J AU Gejman, PV Martinez, M Badner, JA Cao, Q Zhang, J Sanders, AR Cravchik, A Markey, C Guroff, JJ Maxwell, ME Kazuba, D Goldin, LR Gershon, ES AF Gejman, PV Martinez, M Badner, JA Cao, Q Zhang, J Sanders, AR Cravchik, A Markey, C Guroff, JJ Maxwell, ME Kazuba, D Goldin, LR Gershon, ES TI Combined analysis and association of 2 data sets showing evidence for a schizophrenia susceptibility locus an chromosome 6q. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH, Clin Neurogenet Branch, Bethesda, MD 20892 USA. INSERM, F-75654 Paris 13, France. Hop St Louis, Paris, France. RI Martinez, Maria/B-3111-2013 OI Martinez, Maria/0000-0003-2180-4537 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1607 BP A276 EP A276 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001611 ER PT J AU Gerschenson, M Erhart, SW Anderson, LM Diwan, BA Poirier, MC AF Gerschenson, M Erhart, SW Anderson, LM Diwan, BA Poirier, MC TI Inhibition of oxidative phosphorylation (OXPHOS) in fetal heart and kidney mitochondria by transplacental exposure of pregnant mammals to cisplatin or 3 '-azido-2 ',3 '-dideoxythymidine (AZT). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 FCRDC, SAIC, Frederick, MD USA. NCI, Frederick Canc Res & Dev Ctr, LCC, Frederick, MD USA. NIH, LCCTP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2371 BP A405 EP A405 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002372 ER PT J AU Ghosh, S Hauser, E Magnuson, V Valle, T Ally, D Watanabe, R Hagopian, W Bergman, R Tuomilehto, J Collins, F Boehnke, M AF Ghosh, S Hauser, E Magnuson, V Valle, T Ally, D Watanabe, R Hagopian, W Bergman, R Tuomilehto, J Collins, F Boehnke, M TI The fusion (Finland United States investigation of NIDDM genetics) study. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. NHGRI, NIH, Bethesda, MD USA. Natl Publ Hlth Inst, Helsinki, Finland. Univ Washington, Seattle, WA 98195 USA. Univ So Calif, Sch Med, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1611 BP A276 EP A276 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001613 ER PT J AU Glenn, GM Walther, M Choyke, P Humphrey, J Hurley, K Manolatos, A Stolle, CA Zbar, B Linehan, WM AF Glenn, GM Walther, M Choyke, P Humphrey, J Hurley, K Manolatos, A Stolle, CA Zbar, B Linehan, WM TI Genetic diagnostic testing identifies VHL mutations in 62 of 65 kindred: associated family phenotypes show one or more von Hippel-Lindau disease neoplasms of kidney, brain, spine, pancreas, adrenal glands, retina, and inner ear. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2119 BP A362 EP A362 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002119 ER PT J AU Goker-Alpan, O Tifft, C AF Goker-Alpan, O Tifft, C TI Late presentation of VCFS with hypocalcemic seizures and intracerebral calcifications SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD USA. Childrens Natl Med Ctr, Dept Med Genet, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 552 BP A99 EP A99 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000553 ER PT J AU Grabczyk, E Usdin, K AF Grabczyk, E Usdin, K TI Length dependent transcription attenuation is an intrinsic property of the DNA triplet (GAA) expanded in Friedreich's Ataxia SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1806 BP A309 EP A309 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001809 ER PT J AU Graf, M Copenheaver-Hung, D Weinstein, S Chandra, S Tifft, C Krasnewich, D AF Graf, M Copenheaver-Hung, D Weinstein, S Chandra, S Tifft, C Krasnewich, D TI Pena-Shokeir phenotype in an infant with 47,XYY. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Childrens Natl Med Ctr, Washington, DC 20010 USA. Holy Cross Hosp, Silver Spring, MD USA. NIMH, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 553 BP A99 EP A99 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000556 ER PT J AU Green, JS Joyce, C Olufemi, SE Manickam, P Agarwal, SK Guru, SC Kester, MB Marx, SJ Collins, FS Chandrasekharappa, SC AF Green, JS Joyce, C Olufemi, SE Manickam, P Agarwal, SK Guru, SC Kester, MB Marx, SJ Collins, FS Chandrasekharappa, SC TI A common ancestral mutation in four Newfoundland families with the prolactinoma variant of MEN-1 (MEN 1(Burin)). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Mem Univ Newfoundland, Dept Med Genet, St Johns, NF A1C 5S7, Canada. Mem Univ Newfoundland, Dept Endocrinol, St Johns, NF A1C 5S7, Canada. Natl Human Genome Res Inst, Lab Gene Transfer, NIH, Bethesda, MD USA. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 359 BP A67 EP A67 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000360 ER PT J AU Greenberg, F Grimbacher, B Gallin, J Malech, H Puck, J Holland, S AF Greenberg, F Grimbacher, B Gallin, J Malech, H Puck, J Holland, S TI The dysmorphology and genetics of job hyper IgE syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NIAID, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NIAID, Lab Gene Transfer, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 20 BP A6 EP A6 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000020 ER PT J AU Gropman, AL Samango-Sprouse, C Vezina, LG Tifft, CJ AF Gropman, AL Samango-Sprouse, C Vezina, LG Tifft, CJ TI Congenital Bilateral Perisylvian Syndrome (CBPS) in a child with 47,XYY karyotype. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. Childrens Natl Med Ctr, Dept Genet, Washington, DC 20010 USA. Childrens Natl Med Ctr, Dept Radiol, Washington, DC 20010 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2156 BP A368 EP A368 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002158 ER PT J AU Gu, JZ Carstea, E Morris, JA Tagle, D Rosenfeld, MA AF Gu, JZ Carstea, E Morris, JA Tagle, D Rosenfeld, MA TI Isolation and identification of differentially expressed human genes in hamster cells containing a stably integrated human YAC. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Natl Human Genome Res Inst, Lab Gene Transfer, Bethesda, MD USA. NINDS, Dev & Metab Neurol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 994 BP A173 EP A173 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000995 ER PT J AU Guan, XY Jiang, Y Zhang, H Yan, W Meltzer, PS Bittner, M Trent, JM AF Guan, XY Jiang, Y Zhang, H Yan, W Meltzer, PS Bittner, M Trent, JM TI Generation of a complete set of human chromosome band-specific probes (CBPs) by chromosome microdissection. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Natl Human Genome Res Inst, Canc Genet Lab, NIH, Bethesda, MD USA. NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 718 BP A127 EP A127 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000722 ER PT J AU Hacia, JG Edgemon, K Hunt, N Fodor, SPA Brody, LC Collins, FS AF Hacia, JG Edgemon, K Hunt, N Fodor, SPA Brody, LC Collins, FS TI Mutation screening and phylogenetic analysis of hereditary breast cancer genes using high density oligonucleotide arrays. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Natl Human Genome Res Inst, Lab Gene Transfer, NIH, Bethesda, MD USA. Affymetrix Inc, Santa Clara, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 361 BP A67 EP A67 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000361 ER PT J AU Haddad, BR Meck, J Young, H Cowan, J duManoir, S Schrock, E Ried, T AF Haddad, BR Meck, J Young, H Cowan, J duManoir, S Schrock, E Ried, T TI Application of spectral karyotyping in clinical cytogenetics. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Georgetown Univ, Washington, DC USA. NEMC, Boston, MA USA. NHGRI, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 720 BP A127 EP A127 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000723 ER PT J AU Hanson, RL Knowler, WC AF Hanson, RL Knowler, WC CA Pima Diabet Genes Grp TI Variance components and Haseman-Elston sib-pair linkage analyses in a genomic scan for markers linked to obesity. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDDK, Phoenix, AZ USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1620 BP A278 EP A278 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001621 ER PT J AU Hawkins, AL Schrock, E Ried, T Jaffee, E Griffin, CA AF Hawkins, AL Schrock, E Ried, T Jaffee, E Griffin, CA TI Analysis of complex chromosome abnormalities in pancreatic cancer cell lines by multicolor spectral karyotyping (SKY). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD USA. Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD USA. NIH, NIHGR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 366 BP A68 EP A68 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000369 ER PT J AU Hazelwood, S Shotelersuk, V Guo, J Hoganson, G Whitington, PF Gahl, WA AF Hazelwood, S Shotelersuk, V Guo, J Hoganson, G Whitington, PF Gahl, WA TI Evidence for dysregulation of cholesterol and triglyceride synthesis in an infant with fatty liver. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, Sect Human Biochem Genet, HDB, NIH, Bethesda, MD USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD USA. Univ Illinois, Dept Pediat, Chicago, IL USA. Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1463 BP A252 EP A252 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001465 ER PT J AU Hellsten, EO Janne, PA Bernard, DJ Eckhaus, M Owens, J Suchy, SF Pearline, RV Nussbaum, RL AF Hellsten, EO Janne, PA Bernard, DJ Eckhaus, M Owens, J Suchy, SF Pearline, RV Nussbaum, RL TI Mice deficient in Inpp5b, an autosomal phosphatidylinositol bisphosphate 5-phosphatase homologous to the Lowe syndrome protein. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. NHGRI, NIH, Bethesda, MD USA. NIH, Vet Resources Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 140 BP A28 EP A28 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000143 ER PT J AU Henning, KA Novotny, EA Compton, ST Statham, V Liu, PP Rosenfeld, MA AF Henning, KA Novotny, EA Compton, ST Statham, V Liu, PP Rosenfeld, MA TI Production of functional human artificial chromosomes by the modification of YACs containing human centromeric DNA. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2082 BP A355 EP A355 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002082 ER PT J AU Henske, EP Wessner, LL Golden, J Scheithauer, BW Vortmeyer, AO Zhuang, Z Klein-Szanto, AJP Kwiatkowski, DJ Yeung, RS AF Henske, EP Wessner, LL Golden, J Scheithauer, BW Vortmeyer, AO Zhuang, Z Klein-Szanto, AJP Kwiatkowski, DJ Yeung, RS TI Does the two-hit tumor suppressor model apply to divergent cell types in tuberous sclerosis brain and kidney tumors? SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Mayo Clin, Rochester, MN USA. NCI, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 369 BP A68 EP A68 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000368 ER PT J AU Hirotsune, S Chen, X Garrett, L Ledbetter, DH Wynshaw-Boris, A AF Hirotsune, S Chen, X Garrett, L Ledbetter, DH Wynshaw-Boris, A TI Creation of a mouse model of isolated lissencephaly by targeted disruption of Lis1. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Chicago, Ctr Genet Med, Chicago, IL 60637 USA. NHGRI, Lab Genet Dis Res, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 879 BP A154 EP A154 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000883 ER PT J AU Ho, N van Allen, M Taylor, G Francomano, CA AF Ho, N van Allen, M Taylor, G Francomano, CA TI Jeune Asphyxiating Thoracic Dystrophyand Short-rib Polydactyly Type III (Verma-Naumoff) are one and the same disorder. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Univ Toronto, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 564 BP A101 EP A101 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000565 ER PT J AU Hollenbach, JA Thomson, G Bugawan, T Erlich, HA Winkler, C Klitz, W AF Hollenbach, JA Thomson, G Bugawan, T Erlich, HA Winkler, C Klitz, W TI Evolutionary history of HLA and non-HLA markers in Mesoamerican natives. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Frederick, MD 21701 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. Roche Mol Syst, Alameda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 83 BP A17 EP A17 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000084 ER PT J AU Huang, B Ning, Y Sandlin, C Lamb, A Jamehdor, M Ried, T Bartley, J AF Huang, B Ning, Y Sandlin, C Lamb, A Jamehdor, M Ried, T Bartley, J TI Identification of a marker chromosome without detectable alpha satellite sequences by spectral karyotyping. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Genzyme Genet, Long Beach, CA USA. Genzyme Genet, Santa Fe, NM USA. NHGRI, NIH, Bethesda, MD USA. So Calif Permanente Med Grp, Los Angeles, CA 90027 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2178 BP A372 EP A372 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002181 ER PT J AU Imperatore, G Hanson, RL Pettitt, DJ Kobes, S Bennett, PH Knowler, WC AF Imperatore, G Hanson, RL Pettitt, DJ Kobes, S Bennett, PH Knowler, WC CA Pima Diabet Genes Grp TI Segregation and linkage analyses of diabetic nephropathy in Pima Indians. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDDK, NIH, Phoenix, AZ USA. NR 0 TC 4 Z9 5 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1630 BP A280 EP A280 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001632 ER PT J AU Isaacs, WB Xu, J Gronberg, H Smith, JR Carpten, JD Freije, D Isaacs, SD Bova, GS Browstein, MJ Kallioniemi, OP Bailey-Wilson, JE Suzuki, H Stephan, D Walsh, PC Collins, FS Meyers, DA Trent, JM AF Isaacs, WB Xu, J Gronberg, H Smith, JR Carpten, JD Freije, D Isaacs, SD Bova, GS Browstein, MJ Kallioniemi, OP Bailey-Wilson, JE Suzuki, H Stephan, D Walsh, PC Collins, FS Meyers, DA Trent, JM TI Characteristics of families providing evidence of linkage to the Hereditary Prostate Cancer (HPC1) locus on chromosome 1. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Maryland, Ctr Genet Asthma & Complex Dis, Baltimore, MD 21201 USA. Johns Hopkins Univ, James Buchanan Brady Urol Inst, Baltimore, MD 21218 USA. Umea Univ, Dept Oncol, Umea, Sweden. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. RI Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 70 BP A15 EP A15 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000072 ER PT J AU Iwata, T Nuckolls, G Kuznetsov, S Shum, L Slavkin, HC Robey, P Francomano, CA AF Iwata, T Nuckolls, G Kuznetsov, S Shum, L Slavkin, HC Robey, P Francomano, CA TI Fibroblast growth factor receptor 3 (FGFR3) activity in the cells from novel severe skeletal dysplasia patients SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD USA. NIAMS, NIH, Bethesda, MD USA. NIDR, NIH, Bethesda, MD 20892 USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 1 Z9 1 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1963 BP A335 EP A335 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001962 ER PT J AU Jackson, CE Choi, Y Wang, J Fischer, RE Dale, JK Middelton, LA Lenardo, MJ Straus, SE Puck, JM AF Jackson, CE Choi, Y Wang, J Fischer, RE Dale, JK Middelton, LA Lenardo, MJ Straus, SE Puck, JM TI Molecular and functional characterization of Fas mutations in autoimmune lymphoproliferative syndrome (ALPS). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAID, Immunol Genet Sect, Lab Gene Transfer, NIH, Bethesda, MD 20892 USA. NIAID, Med Genet Branch, Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1818 BP A311 EP A311 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001821 ER PT J AU Jain, PK Lalwani, AK Li, XC McDuffie, T Deshmukh, D Verma, IC Wilcox, ER AF Jain, PK Lalwani, AK Li, XC McDuffie, T Deshmukh, D Verma, IC Wilcox, ER TI A gene for recessive nonsyndromic sensorineural hearing impairment (DFNB18) maps to the chromosomal region containing the Usher Syndrome type 1C gene. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDCD, NIH, Rockville, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. All India Inst Med Sci, New Delhi, India. Rotary Deaf Sch, Ichalkaranji Tilwani, Maharashtra, India. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1632 BP A280 EP A280 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001633 ER PT J AU Jaquish, CE Svetkey, LP Vance, JM Wilson, AF AF Jaquish, CE Svetkey, LP Vance, JM Wilson, AF TI Linkage of salt sensitivity and obesity phenotypes in African Americans to marker loci on chromosome 5. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Durham, NC USA. Natl Human Genome Res Inst, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1633 BP A280 EP A280 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001636 ER PT J AU Jia, L Wilkin, DJ Bittner, M Robey, P Young, M Yamada, Y Krizman, D Liotta, L Bonner, R Schuler, G Boguski, M Powell, J Lennon, G Roodman, D Hotchkiss, R Meltzer, P Trent, J Francomano, CA AF Jia, L Wilkin, DJ Bittner, M Robey, P Young, M Yamada, Y Krizman, D Liotta, L Bonner, R Schuler, G Boguski, M Powell, J Lennon, G Roodman, D Hotchkiss, R Meltzer, P Trent, J Francomano, CA TI SGAP: The skeletal genome anatomy project. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD USA. NIDR, NIH, Bethesda, MD USA. NCI, NIH, Bethesda, MD USA. NCRR, NIH, Bethesda, MD USA. NCBI, NIH, Bethesda, MD USA. DCRT, NIH, Bethesda, MD USA. Lawrence Livermore Natl Lab, Lawrence, CA USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Hosp Special Surg, New York, NY 10021 USA. RI Robey, Pamela/H-1429-2011; Bonner, Robert/C-6783-2015 OI Robey, Pamela/0000-0002-5316-5576; NR 0 TC 4 Z9 4 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2212 BP A378 EP A378 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002213 ER PT J AU Kaartinen, K Schleutker, J Matikainen, M Tammela, T Visakorpi, T Kallioniemi, OP AF Kaartinen, K Schleutker, J Matikainen, M Tammela, T Visakorpi, T Kallioniemi, OP TI Androgen receptor genotypes and risk of human prostate cancer. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Tampere Univ, Inst Med Technol, Canc Genet Lab, FIN-33101 Tampere, Finland. TAUH, Tampere, Finland. NHGRI, Canc Genet Lab, NIH, Bethesda, MD 20852 USA. RI Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2120 BP A362 EP A362 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002122 ER PT J AU Kainu, T Tirkkonen, M Kononen, J Johansson, O Loman, N Olsson, H Syrjakoski, K Eerola, HL Heikkila, P Pyrhonen, S Agnarsson, BA Egilsson, V Barkardottir, R Nevanlinna, H Borg, A Kallioniemi, OP AF Kainu, T Tirkkonen, M Kononen, J Johansson, O Loman, N Olsson, H Syrjakoski, K Eerola, HL Heikkila, P Pyrhonen, S Agnarsson, BA Egilsson, V Barkardottir, R Nevanlinna, H Borg, A Kallioniemi, OP TI Somatic genetic and phenotypic characteristics of hereditary breast cancer SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, Canc Genet Lab, NHGRI, Bethesda, MD 20892 USA. Univ Tampere, IMT, Canc Genet Lab, FIN-33101 Tampere, Finland. Univ Lund Hosp, Dept Oncol, S-22185 Lund, Sweden. Helsinki Univ Hosp, Dept Obstet & Gynecol, Helsinki, Finland. Helsinki Univ Hosp, Dept Pathol, Helsinki, Finland. Helsinki Univ Hosp, Dept Oncol, Helsinki, Finland. Univ Hosp Iceland, Dept Pathol, Cell Biol Lab, Reykjavik, Iceland. RI Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 377 BP A70 EP A70 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000378 ER PT J AU Kaler, SG Holmes, CS Kirshman, R Goldstein, DS AF Kaler, SG Holmes, CS Kirshman, R Goldstein, DS TI Plasma neurochemical pattern in pewter and blotchy alleles at the mottled locus, murine homolog of the Menkes disease Occipital horn syndrome gene. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NINDS, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. NHGRI, MGB, NIH, Bethesda, MD USA. Childrens Hosp, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1475 BP A254 EP A254 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001477 ER PT J AU Kallioniemi, A Barlund, M Kononen, J Forozan, F Parsa, NZ Sauter, G Kallioniemi, OP AF Kallioniemi, A Barlund, M Kononen, J Forozan, F Parsa, NZ Sauter, G Kallioniemi, OP TI Contig assembly and identification of positional candidate genes and ESTs at 17q23, a novel recurrent DNA amplification site in human breast cancer. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, Canc Genet Lab, NHGRI, Bethesda, MD 20892 USA. Univ Tampere, Canc Genet Lab, FIN-33101 Tampere, Finland. Univ Basel, Inst Pathol, CH-4003 Basel, Switzerland. RI Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 378 BP A70 EP A70 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000381 ER PT J AU Kaplan, NL Martin, ER Weir, BS Morris, RW AF Kaplan, NL Martin, ER Weir, BS Morris, RW TI Marker selection for the transmission/disequilibrium test in recently admixed populations. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Stat, Program Stat Genet, Raleigh, NC 27695 USA. Analyt Sci Inc, Durham, England. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1166 BP A202 EP A202 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001170 ER PT J AU Karkera, JD Taymans, SE Tumer, G Yoshikawa, T Detera-Wadleigh, SD Wadleigh, RG AF Karkera, JD Taymans, SE Tumer, G Yoshikawa, T Detera-Wadleigh, SD Wadleigh, RG TI Deletions in the glucocorticoid receptor of human multiple myeloma. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Vet Affairs Med Ctr, Med Oncol Sect, Washington, DC 20422 USA. NIMH, Unit Gene Mapping & Express, Clin Neurogenet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 379 BP A70 EP A70 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000379 ER PT J AU Kelly, TE Dawson, PA Marini, JC AF Kelly, TE Dawson, PA Marini, JC TI Extension of phenotype associated with structural mutations in type I collagen: Siblings with juvenile osteoporosis have an alpha 2(I)gly436 -> arg substitution. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Virginia, Dept Pediat, Charlottesville, VA 22903 USA. NICHD, HDB, NIH, Sect Connect Tissue Disorders, Bethesda, MD USA. RI Dawson, Paul/B-1268-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1971 BP A337 EP A337 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001978 ER PT J AU Kimber, WL Hirotsune, S Sutherland, HF Pack, S Garrett, L Chen, A Scambler, PJ Wynshaw-Boris, A AF Kimber, WL Hirotsune, S Sutherland, HF Pack, S Garrett, L Chen, A Scambler, PJ Wynshaw-Boris, A TI Using mouse models for understanding the genetic basis of human 22q11 microdeletion syndromes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Inst Child Hlth, London, England. NIH, Natl Ctr Human Genome Res, LGDR, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. RI Scambler, Peter/C-4998-2008; Pack, Svetlana/C-2020-2014 OI Scambler, Peter/0000-0002-1487-4628; NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 886 BP A155 EP A155 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000887 ER PT J AU Kimonis, VE Franks, WE Herman, K Avakian, A Lin, JP AF Kimonis, VE Franks, WE Herman, K Avakian, A Lin, JP TI Clinical studies and linkage analysis of a Central Illinois family with Autosomal Dominant Optic Atrophy SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 SIU, Sch Med, Dept Pediat, Springfield, IL USA. Ullinois State Police, Div Forens Serv & Idenfificat, Springfield, IL USA. SIU, Ctr Eye, Springfield, IL USA. NIAMS, Genet Studies Sect, Skin Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1634 BP A280 EP A280 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001634 ER PT J AU Kittles, RA Bergen, AW Perola, M Peltonen, L Virkkunen, M Linnoila, M Goldman, D Long, JC AF Kittles, RA Bergen, AW Perola, M Peltonen, L Virkkunen, M Linnoila, M Goldman, D Long, JC TI Y chromosome microsatellite variation in Finland reveals two distinct founding lineages. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Helsinki, FIN-00014 Helsinki, Finland. Natl Publ Hlth Inst, Helsinki, Finland. NIAAA, LNG, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 77 BP A16 EP A16 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000078 ER PT J AU Korczak, JF Kelley, MJ Allikian, KA Shah, AA Goldstein, AM Parry, DM AF Korczak, JF Kelley, MJ Allikian, KA Shah, AA Goldstein, AM Parry, DM TI Genomic screen for linkage in a family with autosomal dominant chordoma. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2343 BP A400 EP A400 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002343 ER PT J AU Krueger, L Hirsch, B AF Krueger, L Hirsch, B TI Timing of replication of FMR1 mediates chromosomal fragility at FRAXA. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Div Clin Sci, NIH, Bethesda, MD USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 740 BP A130 EP A130 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000742 ER PT J AU Kumra, S Wiggs, E Jacobsen, LK Krasnewich, D Smith, ACM Meck, J Bedwell, J Lenane, M Rapoport, JL AF Kumra, S Wiggs, E Jacobsen, LK Krasnewich, D Smith, ACM Meck, J Bedwell, J Lenane, M Rapoport, JL TI An association between sex chromosome anomalies and childhood psychosis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 741 BP A131 EP A131 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000743 ER PT J AU Kundu, G Panda, D Lee, B Peri, A Fohl, D Chakalaparampil, I Mukherjee, B Li, X Mukherjee, D Seides, S Rosenberg, J Star, K Mukherjee, A AF Kundu, G Panda, D Lee, B Peri, A Fohl, D Chakalaparampil, I Mukherjee, B Li, X Mukherjee, D Seides, S Rosenberg, J Star, K Mukherjee, A TI Genetic predictors of coronary restenosis: Potential roles of osteopontin and its receptor gene expression in coronary restenosis after angioplasty. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, HDB, NIH, Bethesda, MD 20892 USA. Washington Hosp Ctr, Washington, DC 20010 USA. McGill Univ, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1824 BP A312 EP A312 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001827 ER PT J AU Lau, EK Castellanos, FX Tayebi, N Lee, P Long, RE Giedd, JN Marsh, WL Ginns, EI Rapoport, JL Sidransky, E AF Lau, EK Castellanos, FX Tayebi, N Lee, P Long, RE Giedd, JN Marsh, WL Ginns, EI Rapoport, JL Sidransky, E TI Association studies do not show an increased frequency of the 7-fold repeat form of the dopamine 4 receptor polymorphism in children with attention deficit hyperactivity disorder (ADHD). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH, Clin Neurosci Branch, IRP, NIH, Bethesda, MD 20892 USA. NIMH, Child Psychiat Branch, IRP, NIH, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 2 Z9 2 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1176 BP A203 EP A203 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001178 ER PT J AU Laundon, CH Ning, Y Ried, T Buchanan, P AF Laundon, CH Ning, Y Ried, T Buchanan, P TI Prenatal diagnosis of a mosaic marker chromosome 14 by spectral karyotyping. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 GeneCare Med Genet Ctr, Chapel Hill, NC USA. NHGRI, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 892 BP A156 EP A156 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000893 ER PT J AU Liang, Y Wang, A Morell, R Wilcox, E Jain, P Li, XC Negrini, C Deshmukh, D Lupski, JR Chen, KS Hinnant, JT Barber, T Winata, S Arhya, IN Moeljopawiro, S Friedman, TB AF Liang, Y Wang, A Morell, R Wilcox, E Jain, P Li, XC Negrini, C Deshmukh, D Lupski, JR Chen, KS Hinnant, JT Barber, T Winata, S Arhya, IN Moeljopawiro, S Friedman, TB TI Nonsyndromic recessive deafness segregating with different haplotypes in families from Bali and India mapped to the 4 cM DFNB3 region of 17p11.2. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDCD, NIH, Rockville, MD USA. Rotary Deaf Sch, Kolhapur, Maharashtra, India. Baylor Coll Med, Houston, TX 77030 USA. Michigan State Univ, E Lansing, MI 48824 USA. Udayana Univ, Denpasar, Bali, Indonesia. Gadjah Mada Univ, IUC Biotechnol, Yogykarta, Indonesia. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1646 BP A282 EP A282 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001646 ER PT J AU Lijam, N Paylor, R McDonald, M Deng, C Larson, D Yasheng, Y Tsang, M Crawley, J Sussman, D Wynshaw-Boris, A AF Lijam, N Paylor, R McDonald, M Deng, C Larson, D Yasheng, Y Tsang, M Crawley, J Sussman, D Wynshaw-Boris, A TI Dishevelled mutant mice: models for human psychiatric disorders and neural tube defects. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD 20892 USA. NIMH, NIH, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD 20892 USA. Univ Maryland, Div Human Genet, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 900 BP A157 EP A157 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000900 ER PT J AU Lin, AY Rioux, JD Nutman, T Daly, M Stone, V Nguyen, H Green, T Hudson, T Zimmerman, PA Fontaine, L Tucker, MA Lander, E Goldstein, AM AF Lin, AY Rioux, JD Nutman, T Daly, M Stone, V Nguyen, H Green, T Hudson, T Zimmerman, PA Fontaine, L Tucker, MA Lander, E Goldstein, AM TI A gene for familiar eosinophilia maps to chromosome 5q31-q33. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. MIT, Whitehead Inst Biomed Res, Ctr Genome Res, Cambridge, MA USA. NIA, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Westat Inc, Rockville, MD USA. RI Tucker, Margaret/B-4297-2015 NR 0 TC 3 Z9 4 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1648 BP A283 EP A283 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001650 ER PT J AU Lin, T Orrison, BM Lewis, RA Nussbaum, RL AF Lin, T Orrison, BM Lewis, RA Nussbaum, RL TI Mutations are not uniformly distributed throughout the OGRL1 gene in Lowe syndrome patients. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Ophthalmol, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1981 BP A338 EP A338 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001980 ER PT J AU Liu, PP Moskowitz, N Rosenfeld, M Henning, KA AF Liu, PP Moskowitz, N Rosenfeld, M Henning, KA TI Humanizing the yeast telomerase template gene TLC1. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2091 BP A357 EP A357 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002095 ER PT J AU Liu, Y Grinberg, A Westphal, H Proia, RL AF Liu, Y Grinberg, A Westphal, H Proia, RL TI Modeling the clinical forms of Gaucher disease: Introduction of human disease mutations by a single insertion mutagenesis procedure (SIMP). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDDK, GBB, Bethesda, MD 20892 USA. NICHD, LMGD, NIH, Bethesda, MD 20892 USA. RI Proia, Richard/A-7908-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1495 BP A257 EP A257 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001496 ER PT J AU Liyanage, M Barlow, C Liu, M Wangsa, D du Manoir, S Green, J Wynshaw-Boris, A Ried, T AF Liyanage, M Barlow, C Liu, M Wangsa, D du Manoir, S Green, J Wynshaw-Boris, A Ried, T TI Models for genetic dissection of tumorigenesis: Ataxia telangiectasia deficient mice and SV40 Large T-Antigen transgenics. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Natl Human Genome Res Inst, Bethesda, MD USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 392 BP A72 EP A72 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000394 ER PT J AU Loftus, SK Morris, JA Carstea, ED Gu, JZ Cummings, C Brown, A Ellison, J Ohno, K Rosenfeld, MA Pentchev, PG Tagle, DA Pavan, WJ AF Loftus, SK Morris, JA Carstea, ED Gu, JZ Cummings, C Brown, A Ellison, J Ohno, K Rosenfeld, MA Pentchev, PG Tagle, DA Pavan, WJ TI Niemann-Pick C, a murine model: Mutations in Npc1 result in abnormal cholesterol homeostasis and neurodegeneration. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Natl Human Genome Res Inst, NIH, Bethesda, MD USA. NINDS, NIH, Bethesda, MD 20892 USA. Tottori Univ, Fac Med, Dept Neurobiol, Yonago, Tottori 683, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1496 BP A257 EP A257 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001499 ER PT J AU Macville, M Heselmeyer, K Van der Linden, M Auer, G Zimonjic, D Popescu, N Schrock, E Ried, T AF Macville, M Heselmeyer, K Van der Linden, M Auer, G Zimonjic, D Popescu, N Schrock, E Ried, T TI Molecular cytogenetic analysis of cervical cancer by interphase in situ hybridization, comparative genomic hybridization and spectral 3 karyotyping. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Genome Technol Branch, NIH, Bethesda, MD USA. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD USA. Karolinska Hosp & Inst, Dept Pathol, Stockholm, Sweden. Leica Imaging Syst, Cambridge, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 754 BP A133 EP A133 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000758 ER PT J AU Marchetti, F Lowe, X Bishop, J Wyrobek, AJ AF Marchetti, F Lowe, X Bishop, J Wyrobek, AJ TI Identification and characterization of chromosomal abnormalities in mouse zygotes that are predictive of pregnancy wastage and de novo translocations at birth. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Calif Lawrence Livermore Natl Lab, BBRP, Livermore, CA USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 755 BP A133 EP A133 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000756 ER PT J AU Marini, JC Forlino, A Cabral, WA AF Marini, JC Forlino, A Cabral, WA TI Metabolism of mutant type I collagen differs in osteoblasts and fibroblasts from two type IV O1 probands. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, HDB, NIH, Sect Connect Tissue Disorders, Bethesda, MD USA. RI Forlino, Antonella/H-5385-2015 OI Forlino, Antonella/0000-0002-6385-1182 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1986 BP A339 EP A339 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001989 ER PT J AU Martin, ER Weir, BS Kaplan, NL AF Martin, ER Weir, BS Kaplan, NL TI Transmission/disequilibrium tests for identifying quantitative trait loci. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 N Carolina State Univ, Dept Stat, Program Stat Genet, Raleigh, NC 27695 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1659 BP A284 EP A284 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001661 ER PT J AU McCormack, SJ Haddad, B Young, H Foster, K Liyanage, M Wangsa, D Liu, L du Manoir, S Lippman, M Trock, B Ried, T Dickson, RL AF McCormack, SJ Haddad, B Young, H Foster, K Liyanage, M Wangsa, D Liu, L du Manoir, S Lippman, M Trock, B Ried, T Dickson, RL TI Whole genome analysis by comparative genomic hybridization and multicolor spectral karyotyping in mammary epithelial cells. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NHGRI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 760 BP A134 EP A134 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000764 ER PT J AU McDowell, GA Touchman, J Anikster, Y Chen, D Isogai, T Green, E Gahl, WA AF McDowell, GA Touchman, J Anikster, Y Chen, D Isogai, T Green, E Gahl, WA TI A high resolution STS and EST map within the cystinosis critical region on human 17p13. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NICHD, Heritable Disorders Branch, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD USA. Helix Res Inst Inc, Chiba, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1388 BP A239 EP A239 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001389 ER PT J AU McDuffie, HH Nordal, R Kirsch, A Nakahara, K Cortopassi, G Pabello, P Ueda, A Gibson, A AF McDuffie, HH Nordal, R Kirsch, A Nakahara, K Cortopassi, G Pabello, P Ueda, A Gibson, A TI Occupational pesticide exposure and genetic instability. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Saskatchewan, Saskatoon, SK S7N 0W0, Canada. United Hosp, St Paul, MN USA. USN, NCI, Bethesda, MD 20084 USA. Univ So Calif, Davis, CA USA. Kagoshima Univ, Kagoshima 890, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2260 BP A386 EP A386 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002260 ER PT J AU McGuire, RE Searby, C Braden, VV Jegathesan, A Marra, M McPherson, JD Ionasescu, V Green, ED AF McGuire, RE Searby, C Braden, VV Jegathesan, A Marra, M McPherson, JD Ionasescu, V Green, ED TI The CMT2D locus on chromosome 7p: Refined genetic localization and high-resolution physical mapping SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Natl Inst Hlth, Bethesda, MD USA. Univ Iowa Hosp, Iowa City, IA USA. Univ Washington, St Louis, MO USA. RI McPherson, John/D-2633-2017 OI McPherson, John/0000-0001-8049-9347 NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1389 BP A239 EP A239 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001392 ER PT J AU McIntosh, I Lichter, PR Clough, MV Roig, CM Wong, D Scott, C Downs, C Stringham, H Boehnke, M Francomano, CA Richards, JE AF McIntosh, I Lichter, PR Clough, MV Roig, CM Wong, D Scott, C Downs, C Stringham, H Boehnke, M Francomano, CA Richards, JE TI Glaucoma and nail patella syndrome (NPS) co-segregate: One gene or two? SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Ctr Med Genet, Baltimore, MD 21205 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD USA. Univ Michigan, WK Kellogg Eye Ctr, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 58 BP A13 EP A13 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000058 ER PT J AU McIntyre, LM Martin, ER Kaplan, NL AF McIntyre, LM Martin, ER Kaplan, NL TI An examination of the TDT for multiple loci. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Div Biometry, Durham, NC 27705 USA. N Carolina State Univ, Dept Stat, Program Stat Genet, Raleigh, NC 27695 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RI McIntyre, Lauren/J-8414-2012 OI McIntyre, Lauren/0000-0002-0077-3359 NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1662 BP A285 EP A285 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001663 ER PT J AU Mendoza-Londono, R Bernal, JE Prieto, JC Morillo, A Biesecker, LG AF Mendoza-Londono, R Bernal, JE Prieto, JC Morillo, A Biesecker, LG TI Brachydactyly type C and bronchiectasis: Report of an apparent association. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Javeriana Univ, Inst Human Genet, Bogota, Colombia. San Ignacio Hosp, Dept Radiol, Bogota, Colombia. HNGRI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 601 BP A107 EP A107 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000604 ER PT J AU Middelton, LA Duffy, JL Smith, ACM Francomano, CA AF Middelton, LA Duffy, JL Smith, ACM Francomano, CA TI Preferences among research subjects about storage and future use of their DNA samples. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 310 BP A58 EP A58 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000311 ER PT J AU Monks, SA Martin, ER Weir, BS Kaplan, NL AF Monks, SA Martin, ER Weir, BS Kaplan, NL TI A sibship test of linkage in the absence of parental information. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1669 BP A286 EP A286 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001672 ER PT J AU Morell, RJ Friedman, TB AF Morell, RJ Friedman, TB TI Modifier genes in Waardenburg syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2376 BP A406 EP A406 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002380 ER PT J AU Ning, Y Huang, B Meck, J Schrock, E Ried, T AF Ning, Y Huang, B Meck, J Schrock, E Ried, T TI Combining spectral karyotyping and subtelomeric probes to improve cytogenetic diagnosis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 George Washington Univ, GeneCare, Washington, DC USA. Genzyme Genet, Long Beach, CA USA. Georgetown Univ, Washington, DC USA. NHGRI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 774 BP A136 EP A136 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000777 ER PT J AU Orvisky, E McKinney, CE Krasnewich, D Eliason, WK Tayebi, N Martin, BM Ginns, EI Sidransky, E AF Orvisky, E McKinney, CE Krasnewich, D Eliason, WK Tayebi, N Martin, BM Ginns, EI Sidransky, E TI Glucosylsphingosine accumulation in the brain, liver, and spleen of type 2 Gaucher mice. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH, Clin Neurosci Branch, IRP, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1503 BP A258 EP A258 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001503 ER PT J AU Padilla-Nash, HM Veldman, T Schrock, E Haas, O Rowley, JD Ried, T AF Padilla-Nash, HM Veldman, T Schrock, E Haas, O Rowley, JD Ried, T TI Chromosomal abnormalities revealed by spectral karyotyping in haematological malignancies. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, Natl Inst Human Genome Res, NHGRI, Bethesda, MD USA. St Anna Kinderspital, Vienna, Austria. Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 418 BP A76 EP A76 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000419 ER PT J AU Pan, CJ Chou, JY AF Pan, CJ Chou, JY TI Elucidation of von Gierke disease using null and wild-type glucose-6-phosphatase mice. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 139 BP A28 EP A28 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000140 ER PT J AU Parry, DM Patronas, N Glenn, GM Duffey, D Oldfield, E Tucker, MA AF Parry, DM Patronas, N Glenn, GM Duffey, D Oldfield, E Tucker, MA TI Autosomal dominant transmission of chordoma in three successive generations. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Ctr Clin, Bethesda, MD USA. Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA. NINDS, Bethesda, MD 20892 USA. RI Tucker, Margaret/B-4297-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 422 BP A77 EP A77 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000424 ER PT J AU Peters, JA Kirsch, I Dimond, E Grogan, L Biesecker, BB Hadley, DW AF Peters, JA Kirsch, I Dimond, E Grogan, L Biesecker, BB Hadley, DW TI The potential relationship of Muir-Torre syndrome (MTS) to hereditary non-polyposis colon cancer (HNPCC). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Natl Naval Med Ctr, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Natl Human Genome Res Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2127 BP A364 EP A364 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002129 ER PT J AU Peterson, RJ Goldman, D Long, JC AF Peterson, RJ Goldman, D Long, JC TI Apportioning global ALDH2 gametic disequilibrium within and among populations and continents. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Penn State Univ, Dept Anthropol, University Pk, PA 16802 USA. NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 79 BP A17 EP A17 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000082 ER PT J AU Philibert, RA Jean, PLS Sahbatou, M Egeland, JA Paul, SM Ginns, EI AF Philibert, RA Jean, PLS Sahbatou, M Egeland, JA Paul, SM Ginns, EI TI A multivariate model using haplotype sharing: Results for bipolar affective disorder in the old order Amish. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. NIMH, Clin Neurosci Branch, IRP, NIH, Bethesda, MD 20892 USA. Fdn Jean Dausset, CEPH, Paris, France. Univ Miami, Sch Med, Dept Psychiat, Hershey, PA USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2350 BP A401 EP A401 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002352 ER EF