FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Olaizola-Horn, S Park, HY Tachibana, M Gilchrest, BA AF Olaizola-Horn, S Park, HY Tachibana, M Gilchrest, BA TI Regulation of microphthalmia transcription factor expression by the protein kinase C and cAMP-dependent pathways in pigment cells. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 569 EP 569 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200608 ER PT J AU Ando, H Funasaka, Y Oka, M Furumura, M Matsunaga, J Matsunaga, N Hearing, VJ Ichihashi, M AF Ando, H Funasaka, Y Oka, M Furumura, M Matsunaga, J Matsunaga, N Hearing, VJ Ichihashi, M TI Fatty acids regulate the proteolytic degradation of tyrosinase. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Kobe Univ, Sch Med, Dept Dermatol, Kobe, Hyogo 650, Japan. NIH, Cell Biol Lab, Bethesda, MD 20892 USA. SUNSTAR Inc, R&D Dept Beauty Care, Osaka, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 574 EP 574 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200639 ER PT J AU Fleischmajer, R MacDonald, ED Perlish, JS Sapadin, AN Yamada, Y AF Fleischmajer, R MacDonald, ED Perlish, JS Sapadin, AN Yamada, Y TI Initiation of skin basement membrane formation involves assembly of laminin-1 and laminin-5 through binding to cell membrane receptors. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIDR, NIH, Bethesda, MD 20892 USA. Mt Sinai Sch Med, Dept Dermatol, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 592 EP 592 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200749 ER PT J AU Wu, K Andreoli, JM Coticchia, CM Markova, NG Steinert, PM Jang, SI AF Wu, K Andreoli, JM Coticchia, CM Markova, NG Steinert, PM Jang, SI TI Analysis of the control of expression and tissue specificity of the human trichohyalin gene. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. SUNY Stony Brook, Dept Oral Biol, Stony Brook, NY 11794 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 605 EP 605 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200825 ER PT J AU Glick, AB Diamond, J Owolabi, T Lam, C AF Glick, AB Diamond, J Owolabi, T Lam, C TI Tetracycline regulated gene expression in the epidermis of transgenic mice expressing the tTA transactivator. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 606 EP 606 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200831 ER PT J AU Lee, JH Whang, KU Wu, K Steinert, PM Jang, SI AF Lee, JH Whang, KU Wu, K Steinert, PM Jang, SI TI Repression of transglutaminase 3 gene expression by a single-stranded DNA binding protein. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Chungnam Natl Univ, Dept Dermatol, Taejon, South Korea. Soonchunhyang Univ, Coll Med, Dept Dermatol, Seoul, South Korea. NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 606 EP 606 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200833 ER PT J AU Saitoh, A Hansen, LA Vogel, JC Udey, MC AF Saitoh, A Hansen, LA Vogel, JC Udey, MC TI Wnt gene expression in murine skin: A possible role for epidermis-derived Wnt-4 in cutaneous epithelial-mesenchymal interactions. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 610 EP 610 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200854 ER PT J AU Boni, R Vortmeyer, AO Park, E Pack, S Zhuang, Z AF Boni, R Vortmeyer, AO Park, E Pack, S Zhuang, Z TI MEN1 gene alterations detected in MEN1-associated and sporadic lipomas SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RI Pack, Svetlana/C-2020-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 613 EP 613 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200874 ER PT J AU Pfutzner, W Hengge, U Ye, J Foster, RA Vogel, JC AF Pfutzner, W Hengge, U Ye, J Foster, RA Vogel, JC TI A model to study topical selection of keratinocytes containing the multi-drug resistance gene. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. Univ Essen Gesamthsch, Essen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 613 EP 613 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200875 ER PT J AU Khan, SG Schneider, TD Kraemer, KH AF Khan, SG Schneider, TD Kraemer, KH TI Splice mutations in xeroderma pigmentosum group C DNA reduce their information content. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 614 EP 614 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200880 ER PT J AU Richard, G Itin, P Bale, SJ DiGiovanna, JJ AF Richard, G Itin, P Bale, SJ DiGiovanna, JJ TI Clinical heterogeneity in erythrokeratodermia variabilis (EKV). SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Basel, Dept Derm, Basel, Switzerland. NIAMS, Genet Studies Sect, LSB, NIH, Bethesda, MD USA. Brown Univ, Rhode Isl Hosp, Dept Derm, Div Dermatopharm, Providence, RI 02903 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 616 EP 616 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200891 ER PT J AU Ye, X Emmert, S Pfutzner, W Kraemer, K Vogel, JC AF Ye, X Emmert, S Pfutzner, W Kraemer, K Vogel, JC TI A model to study correction of point mutations in the endogenous XPA gene using chimeric RNA/DNA oligonucleotides. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Mol Carcinogenesis Lab, Dermatol Branch, Bethesda, MD 20892 USA. NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 616 EP 616 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200894 ER PT J AU Lee, ES Song, HJ Lee, JH Steinert, PM Yang, JM AF Lee, ES Song, HJ Lee, JH Steinert, PM Yang, JM TI A novel glutamic acid to aspartic acid mutation in the end of 2B rod domain in the keratin 1 gene in epidermolytic hyperkeratosis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. Chungnam Natl Univ, Dept Dermatol, Taejon, South Korea. Sungkyunkwan Univ, Dept Dermatol, Seoul, South Korea. Korea Univ, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 617 EP 617 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200897 ER PT J AU Compton, JG DiGiovanna, JJ Bailey, R Austin, F Fleckman, P Bale, SJ AF Compton, JG DiGiovanna, JJ Bailey, R Austin, F Fleckman, P Bale, SJ TI In pursuit of the molecular basis of ichthyosis vulgaris SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Brown Univ, Dept Derm, Providence, RI 02912 USA. NIAMS, IRP, NIH, Bethesda, MD USA. Univ Washington, Dept Med Derm, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 619 EP 619 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200909 ER PT J AU Hwang, ST Boggess, DN Sundberg, JP AF Hwang, ST Boggess, DN Sundberg, JP TI L-Selectin ligand is upregulated in the dermal endothelium of the cpdm/cpdm mouse mutant. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. Jackson Lab, Bar Harbor, ME 04609 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 632 EP 632 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200986 ER PT J AU Saeki, H Sassetti, C Rosen, SD Schall, TJ Hwang, ST AF Saeki, H Sassetti, C Rosen, SD Schall, TJ Hwang, ST TI Fractalkine. A novel CX3C chemokine, is expressed by epidermal melanocytes and Langerhans cells. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. Mol Med Res Inst, Mt View, CA USA. NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 652 EP 652 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738201107 ER PT J AU Boni, R Vortmeyer, AO Zhuang, Z Hofbauer, G Burg, G Pack, S AF Boni, R Vortmeyer, AO Zhuang, Z Hofbauer, G Burg, G Pack, S TI Detection of gene deletion in single metastatic tumor cells in excision margins of melanomas SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. RI Hofbauer, Gunther/B-2671-2010; Pack, Svetlana/C-2020-2014 OI Hofbauer, Gunther/0000-0003-0542-7989; NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 716 EP 716 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738201452 ER PT J AU Horti, AG Koren, AO Ravert, HT Musachio, JL Mathews, WB London, ED Dannals, RF AF Horti, AG Koren, AO Ravert, HT Musachio, JL Mathews, WB London, ED Dannals, RF TI Synthesis of a radiotracer for studying nicotinic acetylcholine receptors: 2-[F-18]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[F-18]A-85380) SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE radiotracer; A-85380; F-18; fluorination; halogen-exchange; nicotinic receptors; acetylcholine; positron emission tomography ID CEREBRAL-CORTEX; BINDING-SITES AB The radiochemical synthesis of 2-[F-18]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[F-18]A-85380, [F-18](1) under bar 1) was accomplished by Kryptofix(R) 222 assisted nucleophilic no-carrier-added [F-18]fluorination of 2-iodo-3-((1-tert-butoxycarbonyl-2 -(S)-azetidinyl)methoxy)pyridine, (2) under bar followed by acidic deprotection. The average radiochemical yield was 10% and the average specific radioactivity was 1050 mCi/mu mol, calculated at end-of-synthesis (EOS). C1 Johns Hopkins Med Inst, Div Nucl Med, Baltimore, MD 21287 USA. Johns Hopkins Med Inst, Div Radiat Hlth Sci, Baltimore, MD 21287 USA. NIDA, Brain Imaging Ctr, Intramural Res Program, Baltimore, MD 21224 USA. RP Horti, AG (reprint author), Johns Hopkins Med Inst, Div Nucl Med, 600 N Wolfe St,Nelson B1-167, Baltimore, MD 21287 USA. NR 23 TC 56 Z9 57 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD APR PY 1998 VL 41 IS 4 BP 309 EP 318 DI 10.1002/(SICI)1099-1344(199804)41:4<309::AID-JLCR78>3.0.CO;2-I PG 10 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA ZG319 UT WOS:000072989600008 ER PT J AU Gulson, BL Mahaffey, KR Jameson, CW Mizon, KJ Korsch, MJ Cameron, MA Eisman, JA AF Gulson, BL Mahaffey, KR Jameson, CW Mizon, KJ Korsch, MJ Cameron, MA Eisman, JA TI Mobilization of lead from the skeleton during the postnatal period is larger than during pregnancy SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID CALCIUM-METABOLISM; BLOOD LEAD; LACTATION; BONE; EXPOSURE AB A cohort of 15 immigrant females to Australia and 7 native Australian controls were monitored on a monthly basis with high-precision lead isotopic methods during gestation and for 6 months after pregnancy to determine the extent of lead mobilization from the maternal skeleton. Quarterly environmental samples of house dust, drinking water, urban air, gasoline, and a 6-day duplicate diet were also measured. The geometric mean blood lead concentration for the immigrant females on arrival in Australia was 3.0 mu g/dl (range: 1.9 to 20 mu g/dl), and for the Australian controls was 3.1 gm/dl (range: 1.9 to 4.3 mu g/dl). During gestation and after pregnancy, blood lead concentrations varied, with mean individual changes of -14% to 83%. For the immigrant subjects, the percentage change in blood lead concentration was significantly greater during the postpregnancy period than during the 2nd and 3rd trimesters (p < 0.001). Skeletal contribution to blood lead, based on the isotopic composition for the immigrant subjects, increased in an approximately linear manner during pregnancy. The mean increases for each individual during pregnancy varied from 26% to 99%. Skeletal lead contribution to blood lead was significantly greater (p < 0.001) during the postpregnancy period than during the 2nd and 3rd trimesters. The contribution of skeletal lead to blood lead during the postpregnancy period remained essentially constant at the increased level of lead mobilization, although the duration of breastfeeding varied from 1 week to more than 6 months. The increased contribution of skeletal lead to blood lead during the postpregnancy period is attributed to increased mobilization of lead from maternal skeletal stores during lactation. The increased contribution of skeletal lead both during pregnancy and in the postpregnancy period is consistent with increased bone resorption, and may be associated with an inadequate calcium intake observed in quarterly 6-day duplicate diets. Mobilization of skeletal lead stores represents a potentially important source of perinatal lead intake and accumulation in the developing fetus. Only two subjects consumed dietary supplements for calcium, and their mobilization of lead from the skeleton to the blood was the lowest of all the subjects. These two subjects' use of calcium supplements may have reduced mobilization of skeletal mineral stores to supply the calcium needs of pregnancy and lactation. Calcium supplementation may be an important means of limiting fetal exposure to lead. C1 Macquarie Univ, Grad Sch Environm, Sydney, NSW 2109, Australia. Macquarie Univ, CSIRO, Div Math & Stat, Sydney, NSW 2109, Australia. Commonwealth Sci & Ind Res Org, Sydney, NSW, Australia. US EPA, Environm Criteria & Assessment Off, Cincinnati, OH 45268 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Garvan Inst Med Res, Bone & Mineral Div, Sydney, NSW, Australia. RP Gulson, BL (reprint author), Macquarie Univ, Grad Sch Environm, Sydney, NSW 2109, Australia. RI Eisman, John/C-2886-2014; Cameron, Murray/C-9970-2009 OI Cameron, Murray/0000-0002-4874-0927 FU NIEHS NIH HHS [N01-ES-05292] NR 22 TC 133 Z9 139 U1 1 U2 6 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD APR PY 1998 VL 131 IS 4 BP 324 EP 329 DI 10.1016/S0022-2143(98)90182-2 PG 6 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA ZK579 UT WOS:000073339300008 PM 9579385 ER PT J AU Ottiger, M Delaglio, F Bax, A AF Ottiger, M Delaglio, F Bax, A TI Measurement of J and dipolar couplings from simplified two-dimensional NMR spectra SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article ID RELAXATION INTERFERENCE; HUMAN UBIQUITIN; SPECTROSCOPY; PROTEIN; CONSTANTS AB Simple procedures are described for recording complementary in-phase and antiphase J-coupled NMR spectra. The sum and difference of these spectra contain only the upheld and the downfield components of a doublet, making it possible to measure the J splitting directly from these combinations without an increase in resonance overlap relative to the decoupled spectrum. The approach is demonstrated for measurement of (1)J(NH) splittings and (2)J(HNC') splittings in oriented and isotropic ubiquitin. Dipolar couplings obtained from differences in the splittings measured in the oriented and isotropic phases are in excellent agreement with dipolar couplings obtained from direct measurement of the splitting or from a conventional E.COSY-type measurement. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Ottiger, M (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NR 23 TC 735 Z9 743 U1 1 U2 43 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD APR PY 1998 VL 131 IS 2 BP 373 EP 378 DI 10.1006/jmre.1998.1361 PG 6 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA ZL914 UT WOS:000073486200027 PM 9571116 ER PT J AU Heidecker, G Munoz, H Lloyd, PA Hodge, DR Pei, GK Rick, SW Brehm, K Ruscetti, FW Kuller, L Polacino, P Hu, SL Morton, WR Benveniste, RE AF Heidecker, G Munoz, H Lloyd, PA Hodge, DR Pei, GK Rick, SW Brehm, K Ruscetti, FW Kuller, L Polacino, P Hu, SL Morton, WR Benveniste, RE TI Sequence diversity of SIVMne Nef in vivo and in vitro SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article; Proceedings Paper CT 15th Annual Symposium on Nonhuman Primate Models for AIDS CY SEP 03-06, 1997 CL SEATTLE, WASHINGTON SP Washington Reg Primate Res Ctr, Natl Ctr Res Resources, NIAID, Caltag Lab, Cellular Prod Inc, Gilead Sci, Immunex Corp, Merck Res Lab, Pathogenesis Corp, PharMingen, SmithKline Beecham, Suburban Surg Co Inc, Anim Specialties Inc DE simian immunodeficiency virus; nef-attenuation ID SIMIAN IMMUNODEFICIENCY VIRUS; RECOMBINANT VACCINIA VIRUS; HIV-1 NEF; LYMPHOCYTE-ACTIVATION; REVERSE-TRANSCRIPTASE; TYPE-1 NEF; SH3 DOMAIN; MACAQUES; REPLICATION; GENE AB We have compared nef gene sequences isolated by PCR from peripheral blood lymphocyte DNA of macaques which had been inoculated with either biologically or molecularly cloned SIVMne. Two samples from each animal obtained either early after infection (week 2-8) or after significant CD4(+) depletion (week 21-137) were analyzed. Three substitutions in the predicted Nef amino acid sequence were seen in all animals at the late time point, and two more in all but one. Two of the common exchanges are located about 40 residues apart in the Nef core sequence, but are in proximity on the tertiary structure as judged by computer modelling using the structure of the HIV Nef core protein as a guide. Most recurring in vivo changes replaced a residue found in the cloned Nef sequence with one present in a consensus derived by aligning the Nef sequences of the SIVsm/HIV-2 groups. Animals inoculated with virus already containing the "late version" nef gene developed a more aggressive disease. The macaque adapted (MA)nef conferred a threefold higher infectivity to the cloned virus, but had no effects on CD4 downregulation. Propagation of virus with MAnef in tissue culture resulted in the rapid emergence of variants with newly attenuated nef. These findings suggest that the selective pressure on nef in vivo and in vitro are different. C1 NCI, Frederick Biomed Supercomp Ctr, SAIC, FCRDC, Frederick, MD 21702 USA. NCI, Lab Leukocyte Biol, Frederick, MD 21702 USA. NCI, Lab Genom Divers, Frederick, MD 21702 USA. Univ Washington, Reg Primate Res Ctr, Seattle, WA 98195 USA. RP Heidecker, G (reprint author), NCI, Frederick Biomed Supercomp Ctr, SAIC, FCRDC, POB B, Frederick, MD 21702 USA. RI Hu, Shiu-Lok/A-3196-2008 OI Hu, Shiu-Lok/0000-0003-4336-7964 NR 34 TC 2 Z9 2 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD APR-JUN PY 1998 VL 27 IS 2-3 BP 73 EP 80 PG 8 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 112UC UT WOS:000075511700005 PM 9747946 ER PT J AU McDowell, GA Town, MM van't Hoff, W Gahl, WA AF McDowell, GA Town, MM van't Hoff, W Gahl, WA TI Clinical and molecular aspects of nephropathic cystinosis SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE cystinosis; transport; linkage; lysosome; storage ID LYSOSOMAL MEMBRANE-GLYCOPROTEINS; CYSTEAMINE THERAPY; GRANULAR FRACTIONS; COUNTER-TRANSPORT; LINKAGE ANALYSIS; FIBROBLASTS; DISEASE; GENE; DEPLETION; MYOPATHY AB Nephropathic cystinosis, an autosomal recessively inherited lysosomal storage disease, results from impaired transport of the disulfide amino acid cystine out of cellular lysosomes. The consequent accumulation and crystallization of cystine destroys tissues, causing growth retardation in infancy, renal failure at 10 years of age, and a variety of other complications. Early oral therapy with the cystine-depleting agent cysteamine prevents renal deterioration and enhances growth. Although the lysosomal cystine carrier has been extensively studied, its molecular structure remains unknown. The lysosomal cystine transporter gene has been mapped by linkage analysis to human chromosome 17p between polymorphic microsatellite markers D17S1583 and D17S1584. Pertinent recombination events and homozygosity by descent has verified that the cystinosis gene lies in the 3.6 cM genetic interval between these two markers. The cystinosis region has been substantially reduced in size by the observation of recombination events in cystinosis patients between markers D17S1828 and D17S2167. According to radiation hybrid analysis, these two markers are separated by 10.2 cR(8000) (centirad using 8000 rad radiation hybrids). Estimates of the physical size of this interval range from 187 to 510 kb. Four yeast artificial chromosomes have been identified which form a contig covering the original cystinosis region. Two P1 clones together may span the new, smaller interval, meaning that the cystinosis gene would lie on one of them. Current efforts are being directed toward using these P1 clones to isolate candidate cDNAs by a variety of methods. The ultimate cloning of the cystinosis gene will reveal how functional lysosomal porters are synthesized, targeted, processed, and integrated into the lysosomal membrane. C1 NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. United Med & Dent Sch Guys & St Thomas Hosp, Guys Hosp, Div Med & Mol Genet, London SE1 9RT, England. Inst Child Hlth, London WC1N 1EH, England. RP Gahl, WA (reprint author), NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, 10 Ctr Dr,MSC 1830, Bethesda, MD 20892 USA. NR 38 TC 16 Z9 17 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD APR PY 1998 VL 76 IS 5 BP 295 EP 302 DI 10.1007/s001090050220 PG 8 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA ZE295 UT WOS:000072777900003 PM 9587063 ER PT J AU Newman, JD AF Newman, JD TI The evolution of communication. SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review C1 NICHHD, Comparat Ethol Lab, NIH, Poolesville, MD 20837 USA. RP Newman, JD (reprint author), NICHHD, Comparat Ethol Lab, NIH, Poolesville, MD 20837 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD APR PY 1998 VL 186 IS 4 BP 251 EP 252 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZG798 UT WOS:000073040800011 ER PT J AU Afshar, G Muraro, PA McFarland, HF Martin, R AF Afshar, G Muraro, PA McFarland, HF Martin, R TI Lack of over-expression of T cell receptor V beta 5.2 in myelin basic protein-specific T cell lines derived from HLA-DR2 positive multiple sclerosis patients and controls SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE multiple sclerosis; myelin basic proteins; T-cell receptors; CD4-positive T-lymphocytes; HLA-DR2 antigens ID GENE REARRANGEMENTS; FINE SPECIFICITY; PEPTIDE; DIVERSITY; USAGE; ENCEPHALOMYELITIS; REPERTOIRE; EXPANSION; CHAIN; IMMUNIZATION AB Based on studies reporting an overexpression of certain V genes in myelin basic protein (MBP)-specific T cells from MS patients, immunotherapies targeting single TCR (V beta 5.2, V beta 6.1) are currently under way. In order to assess the basic assumption for one of these therapeutic strategies, i.e. the overexpression of V beta 5.2 by MBP-specific T cells, we analyzed 100 MBP-specific T cell lines (TCL) for V beta 5.2 expression. Only 4 out of 100 TCL expressed V beta 5.2, and expression of this TCR gene is therefore not more frequent than expected from the normal peripheral blood distribution. Published by Elsevier Science B.V. C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Univ G DAnnunzio, Sch Med, Dept Oncol & Neurosci, I-66100 Chieti, Italy. RP Martin, R (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 10,Room 5B-16,10 Ctr DR MSC 1400, Bethesda, MD 20892 USA. EM rmartin@box-r.nih.gov NR 26 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD APR 1 PY 1998 VL 84 IS 1 BP 7 EP 13 DI 10.1016/S0165-5728(97)00215-4 PG 7 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA ZL021 UT WOS:000073390900002 PM 9600703 ER PT J AU Aizawa, H Wurtz, RH AF Aizawa, H Wurtz, RH TI Reversible inactivation of monkey superior colliculus. I. Curvature of saccadic trajectory SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID EYE-MOVEMENTS; FIXATION CELLS; NEURONS; GENERATION; FIELD; ORGANIZATION; VELOCITY; FEEDBACK; SYSTEM AB The neurons in the intermediate layers of the monkey superior colliculus (SC) that discharge before saccadic eye movements can be divided into at least two types, burst and buildup neurons, and the differences in their characteristics are compatible with different functional contributions of the two cell types. It has been suggested that a spread of activity across the population of the buildup neurons during saccade generation may contribute to the control of saccadic eye movements. The influence of any such spread should be on both the horizontal and vertical components of the saccade because the map of the movement fields on the SC is a two-dimensional one; it should affect the trajectory of saccade. The present experiments used muscimol injections to inactivate areas within the SC to determine the functional contribution of such a spread of activity on the trajectory of the saccades. The analysis concentrated on saccades made to areas of the visual field that should be affected primarily by alteration of buildup neuron activity. Muscimol injections produced saccades with altered trajectories; they became consistently curved after the injection, and successive saccades to the same targets had similar curvatures. The curved saccades showed changes in their direction and speed at the very beginning of the saccade, and for those saccades that reached the target, the direction of the saccade was altered near the end to compensate for the initially incorrect direction. Postinjection saccades had lower peak speeds, longer durations, and longer latencies for initiation. The changes in saccadic trajectories resulting from muscimol injections, along with the previous observations on changes in speed of saccades with such injections, indicate that the SC is involved in influencing the eye position during the saccade as well as at the end of the saccade. The changes in trajectory when injections were made more rostral in the SC than the most active burst neurons also are consistent with a contribution of the buildup neurons to the control of the eye trajectory. The results do not, however, support the hypothesis that the buildup neurons in the SC act as a spatial integrator. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Wurtz, RH (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2A50, Bethesda, MD 20892 USA. NR 34 TC 101 Z9 101 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD APR PY 1998 VL 79 IS 4 BP 2082 EP 2096 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA ZJ987 UT WOS:000073273700041 PM 9535970 ER PT J AU Quaia, C Aizawa, H Optican, LM Wurtz, RH AF Quaia, C Aizawa, H Optican, LM Wurtz, RH TI Reversible inactivation of monkey superior colliculus. II. Maps of saccadic deficits SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID EYE-MOVEMENTS; FIXATION CELLS; STIMULATION; NEURONS; VELOCITY; FIELDS; MODEL AB Neurons in the superior colliculus (SC) are organized as maps of visual and motor space. The companion paper showed that muscimol injections into intermediate layers of the SC alter the trajectory of the movement and confirmed previously reported effects on latency, amplitude, and speed of saccades. In this paper we analyze the pattern of these deficits across the visual field by systematically comparing the magnitude of each deficit throughout a grid of targets covering a large fraction of the visual field. We also translate these deficits onto the SC map of the visual/movement fields to obtain a qualitative estimate of the extent of the deficit in the SC. We found a consistent pattern of substantially increased saccadic latency to targets in the contralateral visual hemifield, accompanied by slight and inconsistent increases and decreases for saccades to the ipsilateral hemifield. The initial and peak speed of saccades was reduced after the injection. The postinjection amplitude of the saccades were either hypometric or normometric, but rarely hypermetric. Although errors in the initial direction of the postinjection saccades were small, they consistently formed a simple pattern: an initial direction with minimal errors (a null direction) separating regions with clockwise and counterclockwise rotations of the initial direction. However, the null direction did not go through the center of the inactivated zone, as would be expected if the SC alone were determining saccade direction, e.g., with a population code. One hypothesis that can explain the misalignment of the null direction with the lesion site is that another system, acting in parallel with the SC, contributes to the determination of saccadic trajectory. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Wurtz, RH (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2A50, Bethesda, MD 20892 USA. NR 31 TC 69 Z9 69 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD APR PY 1998 VL 79 IS 4 BP 2097 EP 2110 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA ZJ987 UT WOS:000073273700042 PM 9535971 ER PT J AU Murphy, DD Cole, NB Greenberger, V Segal, M AF Murphy, DD Cole, NB Greenberger, V Segal, M TI Estradiol increases dendritic spine density by reducing GABA neurotransmission in hippocampal neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE hippocampus; dendritic spines; interneuron; estrogen receptors; GABA; cultures ID GLUTAMIC-ACID DECARBOXYLASE; MESSENGER-RNA LEVELS; RAT-BRAIN; FEMALE RATS; PROGESTERONE; EXPRESSION; ESTROGEN; HORMONES; MEMORY AB We have previously shown that estradiol causes a twofold rise in dendritic spine density in cultured rat hippocampal neurons, as it does in vivo. More recently, estrogen receptors have been localized to aspiny inhibitory hippocampal interneurons, indicating that their effect on spiny pyramidal neurons may be indirect. We therefore examined the possibility that estradiol affects spine density by regulating inhibition in cultured hippocampal interneurons. Immunocytochemically, estrogen receptors were found to be co-localized with glutamate decarboxylase (GAD)-positive neurons (similar to 21% of total neurons in the culture), Exposure of cultures to estradiol for 1 d caused a marked decrease (up to 80%) in the GAD content of the interneurons, measured both by immunohistochemistry and Western blotting, Also, the number of GAD-positive neurons in the cultures decreased to 12% of the total cell population. Moreover, GABAergic miniature IPSCs were reduced in both size and frequency by estradiol, whereas miniature EPSCs increased in frequency, We then mimicked the proposed effects of estradiol by blocking GABA synthesis with mercaptopropionic acid (MA). Cultures treated with MA expressed a dose-dependent decrease in GABA immunostaining that mimicked that seen with estradiol, MA-treated cultures displayed a significant 50% increase in dendritic spine density over controls, similar to that produced by estradiol, These results indicate that estradiol decreases GABAergic inhibition in the hippocampus, which appears to effectively increase the excitatory drive on pyramidal cells, and thus may provide a mechanism for formation of new dendritic spines. C1 Natl Inst Neurol Dis & Stroke, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Weizmann Inst Sci, Dept Neurobiol, IL-71600 Rehovot, Israel. RP Murphy, DD (reprint author), Natl Inst Neurol Dis & Stroke, Neurobiol Lab, NIH, Bldg 36,Room 2A25, Bethesda, MD 20892 USA. NR 36 TC 318 Z9 327 U1 1 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 1 PY 1998 VL 18 IS 7 BP 2550 EP 2559 PG 10 WC Neurosciences SC Neurosciences & Neurology GA ZE302 UT WOS:000072778700024 PM 9502814 ER PT J AU Fueshko, SM Key, S Wray, S AF Fueshko, SM Key, S Wray, S TI GABA inhibits migration of luteinizing hormone-releasing hormone neurons in embryonic olfactory explants SO JOURNAL OF NEUROSCIENCE LA English DT Article DE GABA; GnRH; olfactory; peripherin; tetrodotoxin; immunocytochemistry ID GAMMA-AMINOBUTYRIC-ACID; CEREBELLAR GRANULE CELLS; SUBUNIT MESSENGER-RNAS; RAT-BRAIN; RECEPTOR SUBUNITS; CORTICAL-NEURONS; LHRH NEURONS; EXPRESSION; SYSTEM; CULTURES AB During development, a subpopulation of olfactory neurons transiently expresses GABA. The spatiotemporal pattern of GABAergic expression coincides with migration of luteinizing hormone-releasing hormone (LHRH) neurons from the olfactory pit to the CNS. In this investigation, we evaluated the role of GABAergic input on LHRH neuronal migration using olfactory explants, previously shown to exhibit outgrowth of olfactory axons, migration of LHRH neurons in association with a subset of these axons, and the presence of the olfactory-derived GABAergic neuronal population. GABA(A) receptor antagonists bicuculline (10(-5) M) or picrotoxin (10(-4) M) had no effect On the length of peripherin-immunoreactive olfactory fibers or LHRH cell number. However, LHRH cell migration, as determined by the distance immunopositive cells migrated from olfactory pits, was significantly increased by these perturbations. Addition of tetrodotoxin (10(-6) M), to inhibit Na+-transduced electrical activity, also significantly enhanced LHRH migration. The most robust effect observed was dramatic inhibition of LHRH cell migration in explants cultured in the presence of the GABA(A) receptor agonist muscimol (10(-4) M). This study demonstrates that GABAergic activity in nasal regions can have profound effects on migration of LHRH neurons and suggests that GABA participates in appropriate timing of LHRH neuronal migration into the developing brain. C1 Natl Inst Neurol Dis & Stroke, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Wray, S (reprint author), Natl Inst Neurol Dis & Stroke, Neurochem Lab, NIH, Bldg 36,Room 4D-12, Bethesda, MD 20892 USA. OI wray, susan/0000-0001-7670-3915 NR 52 TC 85 Z9 86 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 1 PY 1998 VL 18 IS 7 BP 2560 EP 2569 PG 10 WC Neurosciences SC Neurosciences & Neurology GA ZE302 UT WOS:000072778700025 PM 9502815 ER PT J AU Shidara, M Aigner, TG Richmond, BJ AF Shidara, M Aigner, TG Richmond, BJ TI Neuronal signals in the monkey ventral striatum related to progress through a predictable series of trials SO JOURNAL OF NEUROSCIENCE LA English DT Article DE ventral striatum; motivation; schedule length; reward; visual cue; information analysis; macaque monkey; neurophysiology ID TEMPORAL CORTEX; RHESUS-MONKEY; REWARD; EXPECTATION; PROJECTIONS AB Single neurons in the ventral striatum of primates carry signals that are related to reward and motivation. When monkeys performed a task requiring one to three bar release trials to be completed successfully before a reward was given, they seemed more motivated as the rewarded trials approached; they responded more quickly and accurately. When the monkeys were cued as to the progress of the schedule, 89 out of 150 ventral striatal neurons responded in at least one part of the task: (1) at the onset of the visual cue, (2) near the time of bar release, and/or (3) near the time of reward delivery, When the cue signaled progress through the schedule, the neuronal activity was related to the progress through the schedule, For example, one large group of these neurons responded in the first trial of every schedule, another large group responded in trials other than the first of a schedule, and a third large group responded in the first trial of schedules longer than one. Thus, these neurons coded the state of the cue, i.e., the neurons carried the information about how the monkey was progressing through the task. The differential activity disappeared on the first trial after randomizing the relation of the cue to the schedule. Considering the anatomical loop structure that includes ventral striatum and prefrontal cortex, we suggest that the ventral striatum might be part of a circuit that supports keeping track of progress through learned behavioral sequences that, when successfully completed, lead to reward. C1 NIMH, Bethesda, MD 20892 USA. Electrotech Lab, Neurosci Sect, Tsukuba, Ibaraki 305, Japan. RP Richmond, BJ (reprint author), NIMH, Bldg 49,Room 1B80, Bethesda, MD 20892 USA. NR 24 TC 154 Z9 155 U1 2 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 1 PY 1998 VL 18 IS 7 BP 2613 EP 2625 PG 13 WC Neurosciences SC Neurosciences & Neurology GA ZE302 UT WOS:000072778700030 PM 9502820 ER PT J AU Zhao, BY Schwartz, JP AF Zhao, BY Schwartz, JP TI Involvement of cytokines in normal CNS development and neurological diseases: Recent progress and perspectives SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Review DE stroke; multiple sclerosis; Alzheimer's disease; transgenic mice; inflammation ID CENTRAL-NERVOUS-SYSTEM; MESSENGER-RNA EXPRESSION; LONG-TERM POTENTIATION; TUMOR-NECROSIS-FACTOR; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; PROMOTES CHOLINERGIC DIFFERENTIATION; LEUKEMIA INHIBITORY FACTOR; TRANSGENIC MICE; ALZHEIMERS-DISEASE; GROWTH-FACTOR AB Cytokines have been recognized to play an important role both in normal development of the brain. when they act as neurotrophic factors, as well as following injury, While both the cytokines and their receptors are synthesized and expressed in the brain normally (albeit at low levels), it has become clear that elevated levels are associated with many neurological disorders, In this review we have chosen to present the data for only a few of the cytokines, including interleukin-1 beta, interleukin-3, interleukin-6, interferon-gamma, transforming growth factor-beta, and tumor necrosis factor-alpha. Data are presented that suggest roles they may play in human disorders, including stroke, multiple sclerosis, Alzheimer's disease, and several psychiatric disorders, The results in human disease are compared with results obtained in a variety of transgenic animal models, The mouse models have very different disorders depending on whether a cytokine is overexpressed either peripherally or in either astrocytes or neurons, The potential significance of this to the understanding of human disease is discussed. (C) 1998 Wiley-Liss, Inc.dagger. C1 NINDS, Clin Neurosci Branch, Mol Genet Sect, NIH, Bethesda, MD 20892 USA. RP NINDS, Clin Neurosci Branch, Mol Genet Sect, NIH, Bldg 10,Room 3N256, Bethesda, MD 20892 USA. EM jps@helix.nih.gov NR 129 TC 150 Z9 156 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0360-4012 EI 1097-4547 J9 J NEUROSCI RES JI J. Neurosci. Res. PD APR 1 PY 1998 VL 52 IS 1 BP 7 EP 16 DI 10.1002/(SICI)1097-4547(19980401)52:1<7::AID-JNR2>3.0.CO;2-I PG 10 WC Neurosciences SC Neurosciences & Neurology GA ZF395 UT WOS:000072893200002 PM 9556025 ER PT J AU Oldfield, EH AF Oldfield, EH TI Pituitary adenomas - Response SO JOURNAL OF NEUROSURGERY LA English DT Letter C1 NINDS, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD APR PY 1998 VL 88 IS 4 BP 789 EP 789 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA ZD078 UT WOS:000072649200029 ER PT J AU Ernst, M Freed, ME Zametkin, AJ AF Ernst, M Freed, ME Zametkin, AJ TI Health hazards of radiation exposure in the context of brain imaging research: Special consideration for children SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE biological risks; ionizing radiation; linear no-threshold model; health hazards; radiation exposure ID BONE-MINERAL CONTENT; LUNG-CANCER; HUMAN-LYMPHOCYTES; IONIZING-RADIATION; ADAPTIVE RESPONSE; CHILDHOOD IRRADIATION; RADON EXPOSURE; X-RAYS; LEUKEMIA; MORTALITY AB This review provides information on health and biological effects of low-dose radiation to help institutional review boards and investigators make educated assessments of the risks of low-level radiation exposure involved in research, particularly in children, Methods: Studies of low-level radiation exposure with large sample sizes and long follow-up were reviewed, To help interpret the studies, we clarified the measures and measurement strategies of radiation exposure and of health risks, The few large studies of risks of low-level radiation in children have failed to detect an increased incidence of cancer, Most studies of low-level radiation involve adults, Results: The risk of increased rates of cancer after low-level radiation exposure is not supported by population studies of health hazards from exposure to background radiation, radon in homes, radiation in the workplace or radiotherapy, Compared to the frequency of daily spontaneous genetic mutations, the biological effect of low-level radiation at the cellular level seems extremely low, Furthermore, the potentiation of cellular repair mechanisms by low-level radiation may result in a protective effect from subsequent high-level radiation, Studies approved by institutional review boards in the U.S. that involve the exposure of healthy normal children to ionizing radiation were reviewed, Conclusion: Health risks from low-level radiation could not be detected above the "noise" of adverse events of everyday life, In addition, no data were found that demonstrated higher risks with younger age at low-level radiation exposure. C1 NIDA, IRP, Brain Imaging Ctr, Baltimore, MD 21224 USA. NIH, Bethesda, MD 20892 USA. RP Ernst, M (reprint author), NIDA, IRP, Brain Imaging Ctr, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 56 TC 14 Z9 14 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD APR PY 1998 VL 39 IS 4 BP 689 EP 698 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZG019 UT WOS:000072956600035 PM 9544683 ER PT J AU Carpenter, CL Morgenstern, H London, SJ AF Carpenter, CL Morgenstern, H London, SJ TI Alcoholic beverage consumption and lung cancer risk among residents of Los Angeles County SO JOURNAL OF NUTRITION LA English DT Article DE humans; epidemiology; lung cancer; alcohol ID BETA-CAROTENE; DIETARY; SMOKING; HABITS; MALES; DEATH AB Although studies generally support a positive association between alcohol consumption and lung-cancer risk, the relationship between specific alcoholic beverages and lung-cancer risk has been inconsistent, We examined recent and past alcoholic beverage intake among 261 incident cases and 615 population controls enrolled in a lung-cancer case-control study of African Americans and Caucasians in Los Angeles County between 1991 and 1994. An in-person interview elicited information about past alcohol intake from ages 30 to 40 y, smoking, other lung-cancer risk factors, as well as recent intake of alcohol, and recent dietary intake, An association was observed between recent hard-liquor consumption and lung-cancer risk. The odds ratio (OR) for 1 or more drinks (1.5 oz or 0.051 mL) per day of hard liquor compared with infrequent liquor drinking (0-3 drinks per month), adjusted for smoking, the matching factors, saturated fat and other alcoholic beverages was 1.87 [95% confidence interval (CI) = 1.02-3.42]. No appreciable association was observed for total alcohol, whereas small inverse associations were observed for beer and wine, although confidence intervals were wide. An elevated lung-cancer risk was also observed for past liquor consumption (between ages 30 and 40 y). The adjusted OR for 1 or more drinks per day of liquor compared with infrequent drinkers was 1.83 (95% CI = 1.06-3.15). Confounding of the association between alcohol and lung cancer by smoking was apparent. Although we devoted considerable efforts to adjusting for smoking in our analyses, residual confounding is still possible because smoking and alcohol are closely associated. In addition, case-control studies including this study should be viewed with caution because of possible selection bias. An increased risk of lung cancer might occur with moderate drinking of hard liquor but confirmation is required in larger studies. C1 Univ So Calif, Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Carpenter, CL (reprint author), Univ So Calif, Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. OI London, Stephanie/0000-0003-4911-5290 FU NCI NIH HHS [N01-CN-25403]; NIDA NIH HHS [DA07272] NR 40 TC 35 Z9 36 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD APR PY 1998 VL 128 IS 4 BP 694 EP 700 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZG518 UT WOS:000073011700006 PM 9521630 ER PT J AU Jacot, JL Hosotani, H Glover, JP Lois, N Robison, WG AF Jacot, JL Hosotani, H Glover, JP Lois, N Robison, WG TI Diabetic-like corneal sensitivity loss in galactose-fed rats ameliorated with aldose reductase inhibitors SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID RETINAL CAPILLARIES; CLOSED VITRECTOMY; PARS-PLANA; COMPLICATIONS; TOLRESTAT; PREVENTION; CT-112; RETINOPATHY; CATARACTS; NERVE AB This study investigated whether diabetic-like corneal sensory deficits occur in the galactose-fed rat model of diabetic ocular complications and if such deficits could be prevented using either of two structurally different aldose reductase (AR) inhibitors, CT-112 or AL-1576. S-D rats were randomly grouped to receive a diet of Purina chow with either 50% starch (n=25) or 50% D-galactose (n=65). Some of the galactosemic rats received either 0.25% CT-112 topically 3x daily (n=15) or 28 mg/kg body wt/day AL-1576 systemically (n=10). The control and untreated galactosemic rats in the CT-112 portion of the study received equivalent topical doses of the vehicle. Sensitivity measurements were made with a Cochet-Bonnet Aesthesiometer mounted on a micromanipulator. The filament was applied to the central corneal surface (mean pressure of 0.96 g/mm(2)) and viewed using a slit-lamp biomicroscope. Ten consecutive stimuli were conducted on each cornea and the average number of blink-responses was expressed as a percent of total stimuli effected. Mean initial corneal sensitivities were similar in all groups. Corneal sensitivity in the galactosemic rat was reduced (p<0.01) at each monthly measurement compared to control. Animals treated with CT-112 or AL-1576 showed a significant increase in the mean blink-response compared to untreated galactose-fed rats and did not differ significantly from controls towards the completion of the 7 month study. Animals treated with AL-1576 did not develop cataracts, whereas those treated topically with CT-112 and untreated galactose-fed rats developed bilateral nuclear cataracts within 3 weeks. This is the first study to demonstrate decreased corneal sensitivity in the galactose-fed rat model and its amelioration with AR inhibitors. Thus, aldose reductase, the first enzyme of the polyol pathway, may have an important role in the pathogenesis of decreased corneal sensitivity. The model could be useful for investigating the pathogenic mechanism(s) involved in reduced corneal sensitivity associated with diabetic keratopathy in humans. C1 NEI, Pathophysiol Sect, NIH, Bethesda, MD 20892 USA. RP Jacot, JL (reprint author), NEI, Pathophysiol Sect, NIH, Bldg 6,Room 320,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 48 TC 14 Z9 15 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1080-7683 J9 J OCUL PHARMACOL TH JI J. Ocular Pharmacol. Ther. PD APR PY 1998 VL 14 IS 2 BP 169 EP 180 DI 10.1089/jop.1998.14.169 PG 12 WC Ophthalmology; Pharmacology & Pharmacy SC Ophthalmology; Pharmacology & Pharmacy GA ZH290 UT WOS:000073092500009 PM 9572543 ER PT J AU Kissinger, JC Collins, WE Li, J McCutchan, TF AF Kissinger, JC Collins, WE Li, J McCutchan, TF TI Plasmodium inui is not closely related to other quartan Plasmodium species SO JOURNAL OF PARASITOLOGY LA English DT Article ID CIRCUMSPOROZOITE PROTEIN GENE; EVOLUTIONARY ORIGIN; IDENTIFICATION; MALARIAS AB Plasmodium inui (Halberstaedter and von Prowazek, 1907), a malarial parasite of Old world monkeys that occurs in isolated pockets throughout the Celebes, Indonesia, Malaysia, and the Philippines. has traditionally been considered to be related more closely to Plasmodium malariae of humans (and its primate counterpart Plasmodium brasiliantum), than to other primate Plasmodium species. This inference was made in part because of the similarities in the periodicities or duration of the asexual cycle in the blood, the extended sporogonic cycle, and the longer period of time for development of the pre-erythrocytic stages in the liver Both P. inui and P. malariae have quartan (72 hr) periodicities associated with their asexual cycle, whereas other primate malarias, such as Plasmodium fragile and Plasmodium cynomolgi, are associated with tertian periodicities (48 hr), and Plasmodium knowlesi, with a quotidian (24 hr) periodicity. Phylogenetic analyses of portions of orthologous small subunit ribosomal genes reveal that P. inui is actually mon closely related to the Plasmodium species of the "vivax-type" lineage than to P. malariae. Ribosomal sequence analysis of many different, geographically isolated, antigenically distinct P. inui isolates reveals that the isolates are nearly identical in sequence and thus members of the same species. C1 FIOCRUZ, Ctr Pesquisas Rene Rachou, Lab Malaria, BR-30190002 Belo Horizonte, MG, Brazil. NIAID, Growth & Dev Sect, Lab Parasit Dis, NIH, Bethesda, MD 20892 USA. RP Kissinger, JC (reprint author), FIOCRUZ, Ctr Pesquisas Rene Rachou, Lab Malaria, Av Augusto de Lima 1715, BR-30190002 Belo Horizonte, MG, Brazil. RI Kissinger, Jessica/E-9610-2010 OI Kissinger, Jessica/0000-0002-6413-1101 NR 23 TC 10 Z9 10 U1 0 U2 1 PU AMER SOC PARASITOLOGISTS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 0022-3395 J9 J PARASITOL JI J. Parasitol. PD APR PY 1998 VL 84 IS 2 BP 278 EP 282 DI 10.2307/3284482 PG 5 WC Parasitology SC Parasitology GA ZJ986 UT WOS:000073273600011 PM 9576499 ER PT J AU Schito, ML Chobotar, B Barta, JR AF Schito, ML Chobotar, B Barta, JR TI Cellular dynamics and cytokine responses in BALB/c mice infected with Eimeria papillata during primary and secondary infections SO JOURNAL OF PARASITOLOGY LA English DT Article ID DELTA-T-CELLS; NITRIC-OXIDE SYNTHASE; NATURAL-KILLER-CELLS; BLOOD-STAGE MALARIA; CD8+ LYMPHOCYTES-T; GAMMA-INTERFERON; LEISHMANIA-MAJOR; DIFFERENTIAL PRODUCTION; LISTERIA-MONOCYTOGENES; IMMUNE-RESPONSES AB BALB/c mice were infected with the intestinal intracellular parasite Eimeria papillata to characterize lymphocyte responses and cytokine profiles throughout primary and secondary infections. Lymphocytes from the mesenteric lymph node (MLN) and the gastrointestinal tract (GIT) of infected mice were phenotypically analyzed using flow cytometry and immunofluorescence microscopy, respectively. Lymphocytes isolated from the MLN during primary infections of BALB/c mice with E. papillata do not proliferate, compared to day 0 uninfected controls, when stimulated in vitro with conconavalin A and express T(H)2-type cytokines (interleukin [IL]-4 and IL-10) on day 3 PI followed by the release of T(H) 1-type cytokines (IL-2 and interferon-gamma) during patency. In the small intestine, significantly more T cells and their subsets were observed during primary infection. During secondary infections, IL-2 was the only 1 of the 4 cytokines that was expressed earlier and at higher levels in the MLN when compared to primary infections. In the small intestine, significantly more alpha beta(+) and CD8(-) T lymphocytes were observed in mice during secondary infection. Oocyst antigens did not induce cellular proliferation at any rime point during primary or secondary infections. We conclude that primary oral infection of BALB/c mice with E. papillata is associated with localized immunosuppression that may be mediated, in part, by early T(H)2-type cytokines. Immunity to secondary infection may be mediated by intestinal alpha beta(+)CD8(+) T lymphocytes through an IL-2-dependent mechanism. C1 Univ Guelph, Ontario Vet Coll, Dept Pathobiol, Guelph, ON N1G 2W1, Canada. RP Schito, ML (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike,Bldg 4,Room 138, Bethesda, MD 20892 USA. OI Barta, John/0000-0001-6896-2271 NR 61 TC 13 Z9 13 U1 0 U2 2 PU AMER SOC PARASITOLOGISTS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 0022-3395 J9 J PARASITOL JI J. Parasitol. PD APR PY 1998 VL 84 IS 2 BP 328 EP 337 DI 10.2307/3284491 PG 10 WC Parasitology SC Parasitology GA ZJ986 UT WOS:000073273600019 PM 9576507 ER PT J AU Mogayzel, PJ Carroll, JL Loughlin, GM Hurko, O Francomano, CA Marcus, CL AF Mogayzel, PJ Carroll, JL Loughlin, GM Hurko, O Francomano, CA Marcus, CL TI Sleep-disordered breathing in children with achondroplasia SO JOURNAL OF PEDIATRICS LA English DT Article ID CERVICOMEDULLARY COMPRESSION; RESPIRATORY COMPLICATIONS; UNEXPECTED DEATH; APNEA; DECOMPRESSION; INFANTS; OBSTRUCTION AB Objective: Our objective was to characterize sleep-disordered breathing in 88 children with achondroplasia aged 1 month to 12.6 years. Results: At the time of their initial polysomnography, five children had previously undergone tracheostomy, and seven children required supplemental oxygen. Initial polysomnography demonstrated a median obstructive apnea index of 0 (range, 0 to 19.2 apneas/hr). The median number of central apneas with desaturation per study was 0.5 (0 to 49), the median oxygen saturation nadir was 91% (50% to 99%), and the median peak end-tidal pCO(2) was 47 mm Hg (36 to 87 mm Hg). Forty-two children (47.7%) had abnormal initial study results, usually caused by hypoxemia. Two children with severe obstructive sleep apnea eventually required continuous positive airway pressure therapy, and three additional children required tracheostomies. Conclusions: (1) Children with achondroplasia often have sleep-related respiratory disturbances, primarily hypoxemia. (2) The majority do not have significant obstructive or central apnea; however, a substantial minority are severely affected. (3) Tonsillectomy and adenoidectomy decreases the degree of upper airway obstruction in most but not all children with achondroplasia and obstructive sleep apnea. (4) Restrictive lung disease can present at a young age in children with achondroplasia. C1 Johns Hopkins Med Inst, Eudowood Div Pediat Resp Sci, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Anesthesia & Crit Care Med, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. NIH, Natl Human Genome Res Inst, Med Genet Branch, Bethesda, MD 20892 USA. RP Marcus, CL (reprint author), Johns Hopkins Hosp, Eudowood Div Pediat Resp Sci, 600 N Wolfe St,Pk 316, Baltimore, MD 21287 USA. FU NCRR NIH HHS [RR-00052]; NHLBI NIH HHS [R01 HL54621] NR 25 TC 33 Z9 34 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD APR PY 1998 VL 132 IS 4 BP 667 EP 671 DI 10.1016/S0022-3476(98)70358-0 PG 5 WC Pediatrics SC Pediatrics GA ZK453 UT WOS:000073322400022 PM 9580768 ER PT J AU McCrae, RR Yik, MSM Trapnell, PD Bond, MH Paulhus, DL AF McCrae, RR Yik, MSM Trapnell, PD Bond, MH Paulhus, DL TI Interpreting personality profiles across cultures: Bilingual, acculturation, and peer rating studies of Chinese undergraduates SO JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY LA English DT Article; Proceedings Paper CT 104th Annual Convention of the American-Psychological-Association CY AUG 09-13, 1996 CL TORONTO, CANADA SP Amer Psychol Assoc ID UNIVERSITY-STUDENTS; 5-FACTOR MODEL; SELF; DIMENSIONS; VALIDATION; JUDGMENTS; INVENTORY AB Prior research (R. R. McCrae, P. T. Costa, & M. S. M. Yik, 1996) using a Chinese translation of the Revised NEO Personality Inventory suggested substantial differences between Hong Kong and North American undergraduates. Study 1, with a sample of bilingual Hong Kong students (N = 162), showed that prior findings were not due simply to the translation. Study 2, with undergraduates of European and Chinese ancestry living in Canada (N = 633), suggested tl;at most of the differences were cultural in origin. Study 3, which used peer ratings of Chinese students (N = 99), replicated most Study ? results, suggesting that exposure to Canadian culture increased openness, cheerfulness, and prosocial behavior and attitudes. Differences in sense of competence and vulnerability to stress appeared to be due to different cultural standards for judging these traits. Together, the 3 studies illustrate an integrated approach to interpreting personality differences across cultures. C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Univ British Columbia, Dept Psychol, Vancouver, BC, Canada. Chinese Univ Hong Kong, Dept Psychol, Sha Tin 100083, Hong Kong. RP McCrae, RR (reprint author), NIA, Gerontol Res Ctr, NIH, Box 03,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 48 TC 105 Z9 107 U1 2 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-3514 J9 J PERS SOC PSYCHOL JI J. Pers. Soc. Psychol. PD APR PY 1998 VL 74 IS 4 BP 1041 EP 1055 DI 10.1037//0022-3514.74.4.1041 PG 15 WC Psychology, Social SC Psychology GA ZH677 UT WOS:000073136200015 PM 9569658 ER PT J AU Morel, KR AF Morel, KR TI Development and preliminary validation of a forced-choice test of response bias for posttraumatic stress disorder SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID AFFECT RECOGNITION; MEMORY; SCHIZOPHRENIA; VETERANS; PTSD AB This article describes the development and preliminary validation of the Morel Emotional Numbing Test for PTSD (MENT), a forced-choice test for detecting response bias in assessments for posttraumatic stress disorder (PTSD). The differences in MENT error rates among four groups of military veterans applying for monetary compensation for combat-related PTSD and two groups of hospitalized military veterans were investigated (N = 102): (a) disability claimants with veritable self-presentations, who were diagnosed with PTSD; (b) disability claimants with veritable self-presentations, who were not diagnosed with PTSD; (c) older disability claimants (age 63 or older) with veritable self-presentations; (d) disability claimants with suspect self-presentations; (e) chemical-dependent inpatients; and (f) schizophrenic inpatients. Veritable versus suspect grouping among disability claimants was determined by examining MMPI-2 F-K dissimulation index scores. The results indicated that the suspect group produced more errors on the MENT than the credible groups or the hospitalized patient groups (p <.0001). Clinical decision rules were used to evaluate the relative effectiveness of the MENT to identify malingering in the claimant groups. The overall efficiency or hit rate on the MENT was 95.6%. C1 Finch Univ Hlth Sci Chicago Med Sch, N Chicago, IL 60064 USA. RP Morel, KR (reprint author), St Elizabeth Hosp, Ctr Neurosci, NIMH, Neuropsychiat Branch, 2700 Martin Luther King Jr Ave SE, Washington, DC 20032 USA. NR 49 TC 34 Z9 34 U1 1 U2 2 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD APR PY 1998 VL 70 IS 2 BP 299 EP 314 DI 10.1207/s15327752jpa7002_8 PG 16 WC Psychology, Clinical; Psychology, Social SC Psychology GA 102EE UT WOS:000074910700008 PM 9697332 ER PT J AU Phillips, LR Wolfe, TL Malspeis, L Supko, JG AF Phillips, LR Wolfe, TL Malspeis, L Supko, JG TI Analysis of brefeldin A and the prodrug breflate in plasma by gas chromatography with mass selective detection SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE brefeldin A; bio-analysis; gas chromatography/mass spectrometry; pharmacokinetics; anticancer agents; plasma AB Breflate is a water soluble prodrug developed to facilitate parenteral administration of the investigational antineoplastic agent brefeldin A (BFA). Previously, using analytical methods based upon reversed-phase high performance liquid chromatography (HPLC) with low wavelength UV detection or gas chromatography (GC) with electron capture detection following derivatization with heptafluorobutyrylimidazole: it was demonstrated that breflate undergoes rapid and efficient conversion to BFA following bolus i.v. injection in mice and dogs. However, plasma concentrations of the drug and prodrug achieved during the administration of nontoxic doses of breflate to beagle dogs as a 72 h continuous i.v. infusion were undetectable (< 0.1 mu g ml(-1)) by these methods. The sensitivity and specificity required for therapeutic drug level monitoring were achieved by GC with selected-ion mass spectrometry (MS) detection. Breflate, BFA and 1-eicosanol, the latter added to the sample as an internal standard (IS), were extracted from plasma into tert-butyl methyl ether (TBME) and esterified with trifluoroacetic anhydride. Methanol was added to the reaction mixture to effect the convenient removal of excess reagent as the volatile methyl ester during evaporation of the solvent. The residual material was analyzed directly upon reconstitution by capillary GC with automated splitless injection. Electron-ionization (70 eV) MS detection was performed by sequentially scanning ions at m/z 58, 202 and 325. The lowest concentration of either analyte quantified with acceptable reproducibility, as defined by an inter-day R.S.D. of about 20%, was near 10 ng ml(-1) in plasma using a sample volume of 100 mu l. The assay has proven to be sufficiently sensitive, specific and reproducible for the routine analysis of pharmacokinetic specimens acquired during IND (investigational new drug)-directed toxicology studies in dogs. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NCI, Lab Pharmaceut Chem, Div Canc Treatment, Dev Therapeut Program, Frederick, MD 21701 USA. SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Phillips, LR (reprint author), NCI, Lab Pharmaceut Chem, Div Canc Treatment, Dev Therapeut Program, Frederick, MD 21701 USA. NR 9 TC 16 Z9 20 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD APR PY 1998 VL 16 IS 8 BP 1301 EP 1309 DI 10.1016/S0731-7085(97)00142-8 PG 9 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA ZK206 UT WOS:000073296000006 PM 9777604 ER PT J AU Cissel, DS Fraundorfer, PF Beaven, MA AF Cissel, DS Fraundorfer, PF Beaven, MA TI Thapsigargin-induced secretion is dependent on activation of a cholera toxin-sensitive and phosphatidylinositol-3-kinase-regulated phospholipase D in a mast cell line SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PROTEIN-KINASE-C; BASOPHILIC RBL-2H3 CELLS; LIPID 2ND MESSENGERS; MYOSIN LIGHT-CHAIN; PHOSPHATIDYLCHOLINE HYDROLYSIS; PHOSPHATIDATE PHOSPHOHYDROLASE; TYROSINE PHOSPHORYLATION; LEUKEMIA-CELLS; SELECTIVE-INHIBITION; SIGNAL-TRANSDUCTION AB Release of secretory granules by rat RBL-2H3 mast cells is mediated primarily through activation of protein kinase C (PKC) and elevation of cytosolic free calcium ([Ca++](i)). Here, we show that secretion was also dependent on the activation of a cholera toxin-sensitive phospholipase (PL) D in cells stimulated with thapsigargin. Wortmannin, LY294002, butanol, propranolol and Ro31-7549 inhibited responses to variety of secretagogues in a manner consistent with the notion that secretion was regulated by both PLD and PKC in a phosphatidylinositol-3-kinase-dependent manner. The effects of these inhibitors, however, were especially pronounced in cells activated by thapsigargin. This stimulant induced minimal stimulation of PLC but measurable activation of PLD, as assessed by formation of phosphatidylethanol in the presence of ethanol. The activation of PLD was suppressed by inhibitors of phosphatidylinositol-3-kinase and was dependent on a rise in [Ca++](i) because thapsigargin failed to activate PLD and secretion when elevation of [Ca++](i) was blocked. Treatment of cells with cholera toxin resulted in selective and similar enhancements in the activation of PLD and secretion by thapsigargin, whereas stimulation of PLC and PLA, was unaffected. A role for PKC was indicated by the blockade of secretory response to thapsigargin by the PKC inhibitor Ro31-7549 and by the ability of the PKC agonist phorbol-12-myristate-13-acetate to reverse the inhibition of secretion by inhibitors of PLD. Such results suggested that thapsigargin, by causing substantial increases in [Ca++](i), induced secondary signals via PLD and PKC that synergized a calcium signal for secretion. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Cissel, DS (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Rm 8N109, Bethesda, MD 20892 USA. NR 63 TC 30 Z9 30 U1 0 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD APR PY 1998 VL 285 IS 1 BP 110 EP 118 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZG158 UT WOS:000072972200014 PM 9536000 ER PT J AU Kunko, PM French, D Izenwasser, S AF Kunko, PM French, D Izenwasser, S TI Alterations in locomotor activity during chronic cocaine administration: Effect on dopamine receptors and interaction with opioids SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID RAT NUCLEUS-ACCUMBENS; ADENYLYL-CYCLASE ACTIVITY; BRAIN-STIMULATION REWARD; BEHAVIORAL SENSITIZATION; ASSAY METHOD; MORPHINE; DISPOSITION; WITHDRAWAL; NALTREXONE; STRIATUM AB Chronic cocaine administration can produce tolerance or sensitization to locomotor activating effects, depending on the treatment paradigm. The effects of chronic, continuous cocaine were measured on locomotor activity for 1 hr daily for 7 days. Cocaine produced significant increases in locomotor activity 4 hr after osmotic minipumps were implanted, and an even higher level of activity after 24 hr. This was likely a rapid sensitization to the locomotor activating effects of cocaine, because neither brain nor plasma levels of cocaine were significantly altered over the treatment period. By day 4, activity levels diminished, but remained significantly higher than in saline-treated animals. Twenty-four hr after pump removal, there were no changes in dopamine D-1 or D-2 receptor binding, or in dopamine-stimulation of adenylyl cyclase activity in either caudate putamen or nucleus accumbens of cocaine-treated animals. Chronic naltrexone produced a slight, nonsignificant decrease in locomotor activity and when combined with cocaine, produced the same pattern of activity as cocaine alone, but with slightly less stimulation on all days. Morphine produced a smaller increase in activity than cocaine that remained constant throughout the treatment week. Cocaine with morphine was additive, producing greater activity and less tolerance than cocaine alone. Thus, continuous cocaine administration produces a rapid sensitization that is lost over the course of the treatment period, yet does not produce any immediate alterations in dopamine receptors or regulation of adenylyl cyclase. The pattern of behavior is not altered by an opioid antagonist, while the sensitization period appears to be prolonged in the presence of an opioid agonist. C1 Natl Inst Drug Abuse, Psychobiol Sect, Intramural Res Program, NIH, Baltimore, MD USA. RP Izenwasser, S (reprint author), Univ Miami, Sch Med, Dept Neurol, 1501 NW 9th Ave,Room 4061, Miami, FL 33136 USA. RI Izenwasser, Sari/G-9193-2012 NR 53 TC 36 Z9 36 U1 1 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD APR PY 1998 VL 285 IS 1 BP 277 EP 284 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZG158 UT WOS:000072972200036 PM 9536022 ER PT J AU Gerard, HC Branigan, PJ Schumacher, HR Hudson, AP AF Gerard, HC Branigan, PJ Schumacher, HR Hudson, AP TI Synovial Chlamydia trachomatis in patients with reactive arthritis Reiter's syndrome are viable but show aberrant gene expression SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE transcription; Chlamydia; reactive arthritis; Reiter's syndrome; differential gene expression ID POLYMERASE CHAIN-REACTION; MEMBRANE PROTEIN GENE; SEQUENCE-ANALYSIS; TANDEM PROMOTERS; RIBONUCLEIC-ACID; RIBOSOMAL-RNA; DNA; INFECTION; DISEASE; JOINTS AB Objective, We used reverse transcription-polymerase chain reaction (RT-PCR) assays to assess expression of genes from Chlamydia trachomatis in synovial tissues of patients with reactive arthritis (ReA)/Reiter's syndrome (RS) to determine viability/metabolic activity of the bacterium in joints of infected patients. Methods. Synovial biopsies were obtained from 18 patients with ReA, RS, or other arthriticies; nucleic acids from 16 samples were PCR positive for chlamydial chromosomal DNA, RT-PCR assays targeting primary transcripts from C. trachomatis rRNA operons, and mRNA from the bacterial ompI, hsp60, glyQS, and r-protein S5 and L5 genes, were used to characterize viability/metabolic activity. Host actin mRNA was assessed as control in each sample preparation. Results, RT-PCR of host cell actin mRNA in the 18 patient samples confirmed the quality of all RNA preparations. RNA from 14/16 PCR positive samples was positive by RT-PCR for chlamydial rRNA primary transcripts. Each of these same 14 samples was also RT-PCR positive in assays targeting glyQS, r-protein S5 and L5,and hsp60 mRNA. However, none of the 14 samples showing chlamydial rRNA and mRNA was positive for ompl transcripts. Conclusion, Synovial chlamydia are viable/metabolically active, since primary rRNA transcripts and mRNA from chlamydial genes specifying components of the bacterial protein synthetic system were present in most patient samples assayed. Expression of ompl, encoding the major outer membrane protein, is strongly attenuated in persistently infecting synovial chlamydia, while that of hsp60, specifying a highly immunogenic heat shock protein of the organism, is not downregulated. C1 NIAMS, NIH, Arthrit & Rheumatism Branch, Bethesda, MD USA. Univ Penn, Sch Med, Dept Med, Div Rheumatol, Philadelphia, PA 19104 USA. RP Hudson, AP (reprint author), Wayne State Univ, Sch Med, Dept Immunol & Microbiol, Gordon H Scott Hall,540 E Canfield Ave, Detroit, MI 48201 USA. EM ahudson@med.wayne.edu FU NIAMS NIH HHS [AR-42541] NR 51 TC 156 Z9 162 U1 1 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD APR PY 1998 VL 25 IS 4 BP 734 EP 742 PG 9 WC Rheumatology SC Rheumatology GA ZG174 UT WOS:000072974500022 PM 9558178 ER PT J AU Bodwell, JE Webster, JC Jewell, CM Cidlowski, JA Hu, JM Munck, A AF Bodwell, JE Webster, JC Jewell, CM Cidlowski, JA Hu, JM Munck, A TI Glucocorticoid receptor phosphorylation: Overview, function and cell cycle-dependence SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 13th International Symposium of the Journal-of-Steroid-Biochemistry-and-Molecular-Biology - Recent Advances in Steroid Biochemistry and Molecular-Biology CY MAY 25-28, 1997 CL MONACO, MONACO SP Journal Steroid Biochem & Molec Biol ID CHICKEN PROGESTERONE-RECEPTOR; HUMAN ESTROGEN-RECEPTOR; HORMONE-INDUCED HYPERPHOSPHORYLATION; TRANSCRIPTIONAL ACTIVATION; DOWN-REGULATION; INTACT-CELLS; WILD-TYPE; SITES; IDENTIFICATION; BINDING AB All steroid hormone receptors are phosphorylated and undergo hormone-induced hyperphosphorylation. Most phosphorylated residues identified so far are serines in the N-terminal domain. Other residues and domains may also be phosphorylated, e.g. the estrogen receptor is phosphorylated on tyrosine in the hormone-binding domain. Many sites lie in consensus sequences for proline-directed, cell cycle-associated kinases. In some receptors hyperphosphorylation is induced by hormone antagonists as well as agonists, and leads to new phosphorylated sites. With glucocorticoid receptors, hyperphosphorylation is specific for glucocorticoid agonists, follows receptor activation and produces no new sites. Rate studies suggest that hyperphosphorylation is due to accelerated phosphorylation rather than delayed dephosphorylation. Evidence to date indicates that steroid hormone receptor phosphorylation serves not as an on-off switch but modulates function more subtly. Mutations of phosphorylated sites to alanine have been found to decrease activity by 0 to 90%, depending on mutated site, cell type, reporter gene and hormone concentration. With glucocorticoid receptors, some alanine mutants are up to 75% less active in hormone-induced transactivation of certain reporter genes. They are also inactive in hormone-induced repression of transcription of their own gene and down regulation of the receptor protein. Furthermore, they are much less sensitive to degradation. Both basal phosphorylation and hormone-dependent hyperphosphorylation of these receptors are cell cycle-dependent, basal phosphorylation being low in S phase and high in G2/M and hyperphosphorylation the reverse, suggesting a causal relation to the cell cycle-dependence of glucocorticoid activity reported with several cell lines. Hyperphosphorylation appears to be regulated by basal phosphorylation through negative charge in the N-terminal domain, which in S phase is relatively low and permits hyperphosphorylation, but in G2/M is relatively high and blocks hyperphosphorylation. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Dartmouth Med Sch, Dept Physiol, Lebanon, NH 03756 USA. NIEHS, Mol Endocrinol Grp, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Munck, A (reprint author), Dartmouth Med Sch, Dept Physiol, Lebanon, NH 03756 USA. FU NIDDK NIH HHS [DK03535, DK45337, DK47329] NR 37 TC 102 Z9 104 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD APR PY 1998 VL 65 IS 1-6 BP 91 EP 99 DI 10.1016/S0960-0760(97)00185-4 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 100TE UT WOS:000074830800008 PM 9699861 ER PT J AU Hager, GL Smith, CL Fragoso, G Wolford, R Walker, D Barsony, J Htun, H AF Hager, GL Smith, CL Fragoso, G Wolford, R Walker, D Barsony, J Htun, H TI Intranuclear trafficking and gene targeting by members of the steroid/nuclear receptor superfamily SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 13th International Symposium of the Journal-of-Steroid-Biochemistry-and-Molecular-Biology - Recent Advances in Steroid Biochemistry and Molecular-Biology CY MAY 25-28, 1997 CL MONACO, MONACO SP Journal Steroid Biochem & Molec Biol ID GLUCOCORTICOID RESPONSE ELEMENT; TRANSCRIPTION FACTOR ACCESS; TUMOR VIRUS PROMOTER; MMTV PROMOTER; IN-VIVO; SACCHAROMYCES-CEREVISIAE; HISTONE ACETYLATION; NUCLEOSOMAL DNA; CHROMATIN; ACTIVATION AB Upon binding to regulatory elements in mammalian chromosomes, steroid receptors induce specific transitions in the nucleoprotein structure of the template. These transitions reflect, in part, the reorganization of chromatin structure to permit interaction of secondary factors with target sequences in promoter regulatory regions. Steroid receptors represent a class of transcriptional activators that are able to interact with repressed nucleoprotein templates and recruit necessary activities for chromatin remodeling. The ligand-induced movement of nuclear receptors from inactive states, either in the cytoplasm or in the nucleus, to productive interactions with chromatin is complex and likely reflects the interaction with multiple protein complexes and subcellular structures. Regulation of gene expression by nuclear receptors is thus mediated through the subcellular distribution of inactive receptors, the redistribution of activated receptor complexes to appropriate nuclear domains, the reorganization of chromatin structures for interaction with soluble components of the nucleoplasm, and direct protein-protein contacts between receptors and the basal transcription apparatus. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. NIDDK, Lab Cellular Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, Bldg 41,Room B602, Bethesda, MD 20892 USA. NR 37 TC 22 Z9 23 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD APR PY 1998 VL 65 IS 1-6 BP 125 EP 132 DI 10.1016/S0960-0760(97)00178-7 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 100TE UT WOS:000074830800012 PM 9699865 ER PT J AU Hughes, FM Cidlowski, JA AF Hughes, FM Cidlowski, JA TI Glucocorticoid-induced thymocyte apoptosis: Protease-dependent activation of cell shrinkage and DNA degradation SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 13th International Symposium of the Journal-of-Steroid-Biochemistry-and-Molecular-Biology - Recent Advances in Steroid Biochemistry and Molecular-Biology CY MAY 25-28, 1997 CL MONACO, MONACO SP Journal Steroid Biochem & Molec Biol ID DEOXYRIBONUCLEIC-ACID; RAT THYMOCYTES; ICE-LIKE; DEATH; CHROMATIN; IDENTIFICATION; FRAGMENTATION; ENDONUCLEASE; CLEAVAGE; NUCLEASE AB Glucocorticoids are well known to stimulate apoptosis in immature thymocytes. Apoptosis in this and other cells is characterized by cell shrinkage, DNA fragmentation and activation of a class of proteases named caspases. We have utilized the flow cytometer to evaluate the coordinate regulation of cell shrinkage and DNA fragmentation in glucocorticoid-treated rat thymocytes and explore the role of caspases upstream of both changes. The results indicate that the activation of apoptosis by glucocorticoids in a cell population is an asynchronous event with only a percentage of the cells displaying apoptotic characteristics at any given time. Both cell shrinkage and chromatin degradation are tightly coupled with similar proportions of the cells displaying each characteristic. The coordinate appearance of these characteristics may suggest a similar mechanism of regulation. Incubation of thymocytes with the general caspase inhibitor Z-VAD-FMX completely blocked both cell shrinkage and DNA fragmentation in spontaneous and glucocorticoid-induced thymocyte apoptosis, implicating an early upstream role for proteases in the activation of thymocyte apoptosis. Published by Elsevier Science Ltd. C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, NIH, POB 12233,MD E2-02, Res Triangle Pk, NC 27709 USA. EM cidlowski@niehs.nih.gov NR 50 TC 51 Z9 51 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD APR PY 1998 VL 65 IS 1-6 BP 207 EP 217 DI 10.1016/S0960-0760(97)00188-X PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 100TE UT WOS:000074830800022 PM 9699875 ER PT J AU Nicolson, R Awad, G Sloman, L AF Nicolson, R Awad, G Sloman, L TI An open trial of risperidone in young autistic children SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE autistic disorder; risperidone; treatment ID INFANTILE-AUTISM; DOUBLE-BLIND; BEHAVIORAL SYMPTOMS; PLACEBO; CLOMIPRAMINE; HALOPERIDOL; DISORDER AB Objective: To assess the benefits and side effects of risperidone in young autistic children. Method: In this open, prospective trial, subjects were treated with risperidone for 12 weeks. All subjects were started at 0.5 mg daily with individual titration to a maximum of 6 mg or 0.1 mg/kg daily. Behavioral ratings, completed by the investigators and the children's parents, included the Clinical Global Impressions (CGI), Children's Psychiatric Rating Scale, Conners Parent-Teacher Questionnaire, Childhood Autism Rating Scale, and Abnormal involuntary Movement Scale. Results: Ten boys, aged 4.5 to 10.8 years, were enrolled in the study and all completed the 12-week protocol. The mean final dose was 1.3 mg/day (range = 1 to 2.5 mg/day). On the basis of CGI-rated improvement, 8 of the 10 children were considered to be responders. Improvement was also demonstrated on the other scales. Transient sedation was common, and the children gained an average of 3.5 kg over the 12 weeks of the study There was no evidence of either extrapyramidal symptoms or tardive dyskinesia. Conclusions: These results suggest that risperidone may be safe and leads to improvements in several behavioral symptoms in young children with autism, Controlled studies of risperidone in young autistic children are warranted. C1 Univ Toronto, Dept Psychiat, Toronto, ON, Canada. RP Nicolson, R (reprint author), NIMH, Child Psychiat Branch, Bldg 10,Room 3N202,10 Ctr Dr MSC 1600, Bethesda, MD 20892 USA. RI Nicolson, Robert/E-4797-2011 NR 28 TC 98 Z9 101 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD APR PY 1998 VL 37 IS 4 BP 372 EP 376 DI 10.1097/00004583-199804000-00014 PG 5 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA ZD162 UT WOS:000072657600014 PM 9549957 ER PT J AU Kumra, S Jacobsen, LK Lenane, M Karp, BI Frazier, JA Smith, AK Bedwell, J Lee, P Malanga, CJ Hamburger, S Rapoport, JI AF Kumra, S Jacobsen, LK Lenane, M Karp, BI Frazier, JA Smith, AK Bedwell, J Lee, P Malanga, CJ Hamburger, S Rapoport, JI TI Childhood-onset schizophrenia: An open-label study of olanzapine in adolescents SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE olanzapine; clozapine; childhood-onset schizophrenia ID OPEN TRIAL; CLOZAPINE; HALOPERIDOL; CHILDREN; DISORDER; PROGRESS AB Objective: Olanzapine, a potent 5-HT2a/2c, dopamine D1D2D4 antagonist with anticholinergic activity, has a profile of known receptor affinity similar to that of clozapine. This pilot study examined the efficacy of olanzapine for treatment-refractory childhood-onset schizophrenia in eight patients who had received 8-week open-label trials. For comparison, data are included from 15 patients who had received g-week open-label clozapine trials using identical rating instruments (largely by the same raters) in the same treatment setting. Method: Twenty-three children and adolescents with an onset of DSM-III-R schizophrenia by age 12 for whom at least two different typical neuroleptics had been ineffective participated in the two separate studies. Some of the patients were intolerant of clozapine, although it had been effective (n = 4). Patients receiving olanzapine were evaluated over 8 weeks with the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Positive Symptoms, the Scale for the Assessment of Negative Symptoms, and the Clinical Global Impressions Scale for Improvement. Results: For the eight patients who received olanzapine trials, at week 8 there was a 17% improvement in the BPRS total score, a 27% improvement in the Scale for the Assessment of Negative Symptoms, and a 1% improvement in the Scale for the Assessment of Positive Symptoms, relative to "ideal" admission status on typical neuroleptics. In contrast, the magnitude of the effect sizes for each of the clinical ratings was larger at week 6 of the previous clozapine trial than for an 8-week olanzapine trial, relative to admission status on typical neuroleptics. For the four children who had received both clozapine and olanzapine, BPRS total scores were significantly lower at week 6 of clozapine treatment compared with week 6 of olanzapine treatment (p = .03). Conclusion: These data provide preliminary evidence for the efficacy of olanzapine for some children and adolescents with treatment-refractory schizophrenia, but they also suggest the need for a more rigorous double-blind comparison of these two atypical antipsychotics. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NINDS, Bethesda, MD 20892 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Kumra, S (reprint author), NIMH, Child Psychiat Branch, Bldg 10,10 Ctr Dr MSC1600,Room 6N240, Bethesda, MD 20892 USA. OI Malanga, C.J./0000-0003-4808-3995 NR 45 TC 108 Z9 109 U1 7 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD APR PY 1998 VL 37 IS 4 BP 377 EP 385 DI 10.1097/00004583-199804000-00015 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA ZD162 UT WOS:000072657600015 PM 9549958 ER PT J AU Lahey, BB Loeber, R Quay, HC Applegate, B Shaffer, D Waldman, I Hart, EL McBurnett, K Frick, PJ Jensen, PS Dulcan, MK Canino, G Bird, HR AF Lahey, BB Loeber, R Quay, HC Applegate, B Shaffer, D Waldman, I Hart, EL McBurnett, K Frick, PJ Jensen, PS Dulcan, MK Canino, G Bird, HR TI Validity of DSM-IV subtypes of conduct disorder based on age of onset SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE conduct disorder; age of onset; aggression; DSM-IV ID DISRUPTIVE BEHAVIOR DISORDERS; OPPOSITIONAL DEFIANT DISORDER; FIELD TRIALS; DELINQUENCY RISK; III DISORDERS; CHILDREN; ADOLESCENTS; VALIDATION; INFORMANTS; TAXONOMY AB Objective: To present data from the DSM-IV field trials that led to the distinction between subtypes of conduct disorder (CD) that emerge in childhood or adolescence. In addition, data from a household sample were used to attempt to cross-validate these findings. Method: Differences between youths who met criteria for the two subtypes of CD were examined in the field trials sample of 440 youths aged 4 through 17 years and in a household sample of 1,285 youths aged 9 through 17 years. Results: In both samples, there was a steep decline in aggression occurring around an age of onset of 10 years, but the number of nonaggressive behaviors was unrelated to the age of onset of CD. In the field trials sample, youths who met criteria for the adolescent-onset type were more likely to be girls, less likely to meet criteria for oppositional defiant disorder, and less likely to have a family history of antisocial behavior than the childhood-onset type, but these latter findings were not confirmed in the household sample. Conclusions: The DSM-IV approach to subtyping CD distinguishes subgroups that differ markedly in level of physical aggression. The advantages of a developmental approach to subtyping are discussed. C1 Univ Chicago, Dept Psychiat MC 3077, Chicago, IL 60637 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Miami, Coral Gables, FL 33124 USA. Columbia Univ, New York, NY 10027 USA. Emory Univ, Atlanta, GA 30322 USA. Yale Univ, New Haven, CT 06520 USA. Univ Calif Irvine, Irvine, CA 92717 USA. Univ Alabama, Tuscaloosa, AL 35487 USA. NIMH, Bethesda, MD 20892 USA. Univ Puerto Rico, San Juan, PR 00936 USA. Northwestern Univ, Evanston, IL 60208 USA. RP Lahey, BB (reprint author), Univ Chicago, Dept Psychiat MC 3077, 5841 S Maryland Ave, Chicago, IL 60637 USA. OI Jensen, Peter/0000-0003-2387-0650 FU NIMH NIH HHS [R01-MH47200, U01-MH46725] NR 37 TC 126 Z9 126 U1 2 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD APR PY 1998 VL 37 IS 4 BP 435 EP 442 DI 10.1097/00004583-199804000-00022 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA ZD162 UT WOS:000072657600022 PM 9549965 ER PT J AU Kawahara, Y Amagai, M Ohata, Y Ishii, K Hasegawa, Y Hsu, R Yee, C Yancey, KB Nishikawa, T AF Kawahara, Y Amagai, M Ohata, Y Ishii, K Hasegawa, Y Hsu, R Yee, C Yancey, KB Nishikawa, T TI A case of cicatricial pemphigoid with simultaneous IgG autoantibodies against the 180 kd bullous pemphigoid antigen and laminin 5 SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID BASEMENT-MEMBRANE; BP180; IDENTIFICATION; EPILIGRIN; DOMAIN C1 Keio Univ, Sch Med, Dept Dermatol, Shinjuku Ku, Tokyo 160, Japan. Fukui Saiseikai Hosp, Div Dermatol, Fukui, Japan. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Amagai, M (reprint author), Keio Univ, Sch Med, Dept Dermatol, Shinjuku Ku, 35 Shinano Machi, Tokyo 160, Japan. RI Amagai, Masayuki/K-5325-2013 OI Amagai, Masayuki/0000-0003-3314-7052 NR 20 TC 22 Z9 22 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD APR PY 1998 VL 38 IS 4 BP 624 EP 627 DI 10.1016/S0190-9622(98)70129-X PG 4 WC Dermatology SC Dermatology GA ZG324 UT WOS:000072990100017 PM 9555805 ER PT J AU Marquez, VE Ezzitouni, A Russ, P Siddiqui, MA Ford, H Feldman, RJ Mitsuya, H George, C Barchi, JJ AF Marquez, VE Ezzitouni, A Russ, P Siddiqui, MA Ford, H Feldman, RJ Mitsuya, H George, C Barchi, JJ TI HIV-1 reverse transcriptase can discriminate between two conformationally locked carbocyclic AZT triphosphate analogues SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEXOSE-NUCLEIC-ACIDS; NUCLEOSIDE ANALOGS; CRYSTAL-STRUCTURE; SUGAR RING; BIOLOGICAL-ACTIVITY; MOLECULAR-STRUCTURE; SYN CONFORMATION; NEPLANOCIN-C; HOMO-DNA AB It has been proposed that the preference of 3'-azido-3'-deoxythymidine (AZT) for the extreme E-3 (south) conformation, as observed in its X-ray structure, is responsible for its potent anti-HIV activity. However, it has also been suggested that the antipodal north conformation may be required for the strong interaction of AZT 5'-triphosphate with its target enzyme, HIV reverse transcriptase (RT). To resolve this issue, we have constructed two conformationally rigid carbocyclic analogues of AZT which are locked permanently into opposite E-2 (north) and E-3 (south) conformations in order to test the ability of the corresponding 5'-triphosphates to inhibit RT. The two isomeric carbocyclic analogues of AZT, (N)-methano-carba-AZT (1) and (S)-methano-carba-AZT (2), were constructed on a bicyclo[3.1.0]hexane template that exhibits a rigid pseudoboat conformation, capable of mimicking the furanose pucker in the classical north and south conformations that are characteristic of standard nucleosides. The unique conformational properties of 1 and 2 observed by both X-ray and solution NMR studies showed the existence of the same invariant conformations in solution and in the solid state. In addition, differences observed in the outcome of the Mitsunobu inversion of a secondary hydroxyl function attempted with both bicyclo[3.1.0]hexane nucleoside analogues could be explained by the rigid pseudoboat nature of this system. In one case, the bicyclic system facilitated formation of an anhydronucleoside intermediate, whereas in the other it completely prevented its formation. The chemically synthesized 5'-triphosphates of 1 and 2 were evaluated directly as RT inhibitors using both a recombinant enzyme and enzyme obtained and purified directly from wild-type viruses. The results showed that inhibition of RT occurred only with the conformationally locked E-2 (N)-methano-carba-AZT 5'-triphosphate. This inhibition was equipotent to and kinetically indistinguishable from that produced by AZT 5'-triphosphate. The antipodal E-3 (S)-methano-carba-AZT 5'-triphosphate, on the other hand, did not inhibit RT. C1 NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Expt Retrovirol Sect, Med Branch, Div Clin Sci,NIH, Bethesda, MD 20892 USA. USN, Struct Matter Lab, Res Lab, Washington, DC 20375 USA. RP Marquez, VE (reprint author), NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RI Barchi Jr., Joseph/N-3784-2014 NR 55 TC 142 Z9 145 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD APR 1 PY 1998 VL 120 IS 12 BP 2780 EP 2789 DI 10.1021/ja973535+ PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA ZF391 UT WOS:000072892800011 ER PT J AU Slavkin, HC AF Slavkin, HC TI Toward increased sensitivity and specificity in the treatment of neoplastic diseases SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article C1 NIDR, Bethesda, MD 20892 USA. RP Slavkin, HC (reprint author), NIDR, 31 Ctr Dr,MSC 2290,Bldg 31,Room 2C39, Bethesda, MD 20892 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD APR PY 1998 VL 129 IS 4 BP 473 EP 478 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA ZG502 UT WOS:000073010100024 PM 9573699 ER PT J AU Perkowski, LC Stroup-Benham, CA Markides, KS Lichtenstein, MJ Angel, RJ Guralnik, JM Goodwin, JS AF Perkowski, LC Stroup-Benham, CA Markides, KS Lichtenstein, MJ Angel, RJ Guralnik, JM Goodwin, JS TI Lower-extremity functioning in older Mexican Americans and its association with medical problems SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID PERFORMANCE-BASED MEASURES; NON-HISPANIC WHITES; PHYSICAL PERFORMANCE; DIABETIC-RETINOPATHY; ELDERLY PEOPLE; RISK-FACTORS; DISABILITY; HEALTH; DISEASE; PREDICTORS AB OBJECTIVE: To describe lower-extremity functioning in community-dwelling older Mexican Americans and to examine its relationship with medical problems. DESIGN: Cross-sectional analyses of survey and performance-based data obtained in a population-based study employing area probability sampling. SETTING: Households within selected census tracts of five Southwestern states: Arizona, California, Colorado, New Mexico, and Texas. PARTICIPANTS: A total of 2873 Mexican Americans aged 65 years and older. MEASUREMENTS: A multidimensional questionnaire assessing demographic, sociocultural, and health variables. Standardized tests of lower-extremity physical functioning included measures of standing balance, repeated chair stands, walking, and an overall summary measure. RESULTS: Regression analyses revealed that being more than age 75 and female, having arthritis diabetes, visual impairments, or being obese or underweight were all significantly associated with performance on both individual and summary tests of lower-extremity functioning. In separate regression analyses, the total number of medical conditions was also associated with performance. CONCLUSIONS: The likelihood of predicting performance or inability to complete tests of lower-extremity functioning was greatest for those aged 80 and older, those with arthritis or diabetes, and those with three or more medical conditions. Because of the high prevalence of diabetes in Mexican Americans, documentation of the association of diabetes with performance-based tests of lower-extremity functioning may help guide early interventions targeted to prevent progression to more severe limitations or disability. C1 Univ So Calif, Sch Med, Div Med Educ, Los Angeles, CA 90033 USA. Univ Texas, Med Branch, Dept Prevent Med & Community Hlth, Galveston, TX 77550 USA. Univ Texas, Med Branch, Ctr Aging, Galveston, TX 77550 USA. Univ Texas, Hlth Sci Ctr, Div Geriatr & Gerontol, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. Univ Texas, Dept Sociol, Austin, TX 78712 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. RP Perkowski, LC (reprint author), Univ So Calif, Sch Med, Div Med Educ, 1975 Zonal Ave, KAM 211A, Los Angeles, CA 90033 USA. FU NIA NIH HHS [R01-AG10939] NR 62 TC 34 Z9 35 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 1998 VL 46 IS 4 BP 411 EP 418 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA ZG164 UT WOS:000072973100002 PM 9560061 ER PT J AU Stavri, PZ AF Stavri, PZ TI Automating the lexicon: Research and practice in a multilingual environment. SO JOURNAL OF THE AMERICAN SOCIETY FOR INFORMATION SCIENCE LA English DT Book Review C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Stavri, PZ (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0002-8231 J9 J AM SOC INFORM SCI JI J. Am. Soc. Inf. Sci. PD APR PY 1998 VL 49 IS 4 BP 380 EP 381 PG 2 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA ZB384 UT WOS:000072466800008 ER PT J AU Ishii, M Jones, M Shiota, T Yamada, I Heinrich, RS Holcomb, SR El-Kadi, T Yoganathan, AP Sahn, DJ AF Ishii, M Jones, M Shiota, T Yamada, I Heinrich, RS Holcomb, SR El-Kadi, T Yoganathan, AP Sahn, DJ TI What is the validity of continuous wave Doppler grading of aortic regurgitation severity? A chronic animal model study SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID MITRAL REGURGITATION; NONINVASIVE EVALUATION; CONVERGENCE METHOD; ORIFICE AREA; ECHOCARDIOGRAPHY; TIME; QUANTIFICATION; ULTRASOUND AB Continuous wave Doppler methods have been widely used clinically for evaluating the severity of aortic regurgitation; however, there have been no studies comparing these continuous wave Doppler methods with a strictly quantifiable reference for regurgitant severity. The purpose of this study was to test the applicability of continuous wave Doppler methods (deceleration slope and pressure half-time) for evaluation of chronic aortic regurgitation in an animal model. Eight sheep were studied 8 to 20 weeks after surgery to create chronic aortic regurgitation. Twenty-nine hemodynamically different states were obtained pharmacologically. A Vingmed 775 system was used for recording continuous wave Doppler traces with a 5 MHz annular array transducer directly placed on the heart near the apex. The aortic regurgitation was quantified as peak and mean regurgitant flow rates, regurgitant stroke volumes and regurgitant fractions determined with pulmonary and aortic electromagnetic flow probes and meters balanced against each other. Peak regurgitant how rates varied from 1.8 to 13.6 L/min (6.3 +/- 3.2 L/min) (mean a SD), mean regurgitant flow rates varied from 0.7 to 4.9 L/min (2.7 +/- 1.3 L/min), regurgitant stroke volume varied from 7.0 to 48.0 ml/beat (26.9 +/- 12.2 ml/beat), and regurgitant fraction varied from 23% to 78% (53% +/- 16%). Only marginal correlations were obtained between reference indexes and continuous wave Doppler deceleration slope and pressure half-time (I = 0.55 to 0.74). A deceleration slope greater than 3 m/sec(2) and pressure half-time less than 400 msec did, however, provide 100% specificity for detecting severe AR (regurgitant fraction >50%). Our study shows that the continuous wave Doppler deceleration slope and pressure half-time methods have limited use for quantifying aortic regurgitation. C1 Oregon Hlth Sci Univ, Clin Care Ctr Congenital Heart Dis, Portland, OR 97201 USA. NHLBI, Bethesda, MD 20892 USA. Georgia Inst Technol, Atlanta, GA 30332 USA. RP Sahn, DJ (reprint author), Oregon Hlth Sci Univ, Clin Care Ctr Congenital Heart Dis, 3181 SW Sam Jackson Pk Rd,UHN 60, Portland, OR 97201 USA. FU NHLBI NIH HHS [HL 43287] NR 22 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD APR PY 1998 VL 11 IS 4 BP 332 EP 337 DI 10.1016/S0894-7317(98)70100-2 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZH646 UT WOS:000073132800005 PM 9571582 ER PT J AU Teigen, PM AF Teigen, PM TI A biographical history of veterinary pathology. SO JOURNAL OF THE HISTORY OF MEDICINE AND ALLIED SCIENCES LA English DT Book Review C1 Natl Lib Med, Hist Med Div, Bethesda, MD 20895 USA. RP Teigen, PM (reprint author), Natl Lib Med, Hist Med Div, Bethesda, MD 20895 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-5045 J9 J HIST MED ALL SCI JI J. Hist. Med. Allied Sci. PD APR PY 1998 VL 53 IS 2 BP 186 EP 187 PG 2 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA ZK750 UT WOS:000073358800007 ER PT J AU Cronin, KA Weed, DL Connor, RJ Prorok, PC AF Cronin, KA Weed, DL Connor, RJ Prorok, PC TI Case-control studies of cancer screening: Theory and practice SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID BREAST-CANCER; COLORECTAL-CANCER; NIJMEGEN PROJECT; GASTRIC-CANCER; LUNG-CANCER; DOM PROJECT; EFFICACY; MORTALITY; PROGRAM; JAPAN AB This review summarizes methodologic theories for the design of cancer screening case-control studies and examines the methods applied in studies published in English from 1980 through 1996, In addition to summarizing state-of-the-art methodologic approaches, we identify areas where obvious gaps exist between theory and practice, and we recommend potential areas where theory and methodology may need further development, In particular, we focus on three major areas: 1) the selection of case and control subjects, 2) the definition of exposure (i.e., exposure to the screening test), and 3) bias, Each area is considered carefully by summarizing current theory, reviewing cancer screening applications, and linking recommended methodologic approaches to those used in practice to identify areas where inconsistencies exist. In general, we found methodologic theory and practice in this field of research to be consistent. However, discrepancies were identified in the area of exposure definition, including the use of screening frequency and the use of a detectable, curable preclinical phase for case subjects as the exposure measures, Even when recommended methods were followed, a number of difficulties arose in practice, Specific concerns included the ability to carry out the following: identifying all case subjects within a source population, defining eligibility criteria to ensure that case and control subjects had equal access to screening during the exposure period, distinguishing between symptomatic and diagnostic tests, and controlling for self-selection bias, Careful scrutiny is warranted in all aspects of the design of cancer screening case-control studies, and caution is advised in the interpretation of study results. C1 NCI, Biometry Branch, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Cronin, KA (reprint author), NCI, Biometry Branch, NIH, Execut Plaza N,Rm 313, Bethesda, MD 20892 USA. NR 46 TC 51 Z9 51 U1 0 U2 8 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 1 PY 1998 VL 90 IS 7 BP 498 EP 504 DI 10.1093/jnci/90.7.498 PG 7 WC Oncology SC Oncology GA ZE283 UT WOS:000072776500007 PM 9539244 ER PT J AU Helzlsouer, KJ Selmin, O Huang, HY Strickland, PT Hoffman, S Alberg, AJ Watson, M Comstock, GW Bell, D AF Helzlsouer, KJ Selmin, O Huang, HY Strickland, PT Hoffman, S Alberg, AJ Watson, M Comstock, GW Bell, D TI Association between glutathione S-transferase M1, P1, and T1 genetic polymorphisms and development of breast cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID TRANS-STILBENE OXIDE; GSTT1 GENOTYPES; SUSCEPTIBILITY; GSTM1; RISK; EXPRESSION; PI; CARCINOGENESIS; MUTAGENESIS; DELETION AB Background: Glutathione S-transferases (GSTs) are encoded by a superfamily of genes and play a role in the detoxification of potential carcinogens, In a nested case-control study, we investigated associations between genetic variability in specific GST genes (GSTM1, GSTT1, and GSTP1) and susceptibility to breast cancer, Methods: In 1989, a total of 32898 individuals donated blood samples to a research specimen bank established in Washington County, MD, Genotypes of blood specimen DNA were determined for 110 of 115 women with incident cases of breast cancer diagnosed during the period from 1990 through 1995 and up to 113 of 115 control subjects, Associations between specific genotypes and the development of breast cancer were examined by use of logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs), Results: The GSTM1 homozygous null genotype was associated with an increased risk of developing breast cancer (OR = 2.10; 95% CI = 1.22-3.64), principally due to an association with postmenopausal breast cancer (OR = 2.50; 95% CI 1.34-4.65), For GSTP1, the data were suggestive of a trend of increasing risk with higher numbers of codon 105 valine alleles (compared with isoleucine alleles); a 1.97-fold increased risk of breast cancer (95% CI = 0.77-5.02) was associated with valine/valine homozygosity, The risk of breast cancer associated with the GSTT1 homozygous null genotype was 1.50 (95 % CI = 0.76-2.95), The risk of breast cancer increased as the number of putative highrisk genotypes increased (P for trend <.001) (OR = 3.77; 95% CI = 1.10-12.88 for a combined genotype of GSTM1 null, GSTT1 null, and. either GSTP1 valine heterozygosity or GSTP1 valine homozygosity), Conclusions: Our findings suggest that genetic variability in members of the GST gene family may be associated with an increased susceptibility to breast cancer. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. NIEHS, Genet Risk Grp, Lab Computat Biol & Risk Assessment, Res Triangle Pk, NC 27709 USA. RP Helzlsouer, KJ (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, 615 N Wolfe St, Baltimore, MD 21205 USA. FU NCI NIH HHS [CA62988]; NHLBI NIH HHS [HL21670]; NIEHS NIH HHS [ES03819] NR 34 TC 216 Z9 224 U1 0 U2 3 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 1 PY 1998 VL 90 IS 7 BP 512 EP 518 DI 10.1093/jnci/90.7.512 PG 7 WC Oncology SC Oncology GA ZE283 UT WOS:000072776500009 PM 9539246 ER PT J AU Kshirsagar, AV Choyke, PL Linehan, WM Walther, MM AF Kshirsagar, AV Choyke, PL Linehan, WM Walther, MM TI Pseudotumors after renal parenchymal sparing surgery SO JOURNAL OF UROLOGY LA English DT Article DE gelatin sponge, absorbable; kidney neoplasms; nephrectomy; Hippel-Lindau disease ID HIPPEL-LINDAU DISEASE; CELL CARCINOMA; CT AB Purpose: After renal parenchymal sparing surgery, residual defects may persist on imaging studies at the sites of resection. These "pseudotumors" may lead to confusion as to whether a lesion was removed or has recurred. We describe the imaging appearances and behavior of renal pseudotumors following renal parenchymal sparing surgery. Materials and Methods: From 1988 to 1997, 32 patients underwent 46 renal parenchymal sparing surgeries for removal of renal cancers, including von Hippel-Lindau disease in 27, hereditary papillary renal cancer in 2 and sporadic disease in 3. A median of 14 tumors (range 1 to 114) were removed in each operation. Thrombin soaked absorbable gelatin sponge was placed in the tumor bed after resection to aid hemostasis. We reviewed all imaging studies performed after these operations to characterize these lesions and gain further understanding into the prevalence and etiology. Results: Of the patients, 9 had a total 13 pseudotumors on initial postoperative imaging studies, including Hippel-Lindau disease in 7, hereditary papillary renal cancer in 1 and sporadic renal cancer in 1. Pseudotumors were observed after 10 of 46 operations (22%). All pseudotumors demonstrated round contours and enhancement after contrast media, simulating a tumor, yet, these lesions resolved in a mean of 13 months, leaving only small cortical scars. Conclusions: Renal pseudotumors are commonly seen after renal parenchymal sparing surgery and should not be confused with residual or recurrent disease. Enhancement is likely due to granulation tissue involving the lattice of absorbable gelatin sponge. These lesions usually resolve within a year but can take longer to do so. C1 NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Dept Radiol, NIH, Bethesda, MD 20892 USA. RP Kshirsagar, AV (reprint author), NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 14 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD APR PY 1998 VL 159 IS 4 BP 1148 EP 1151 DI 10.1016/S0022-5347(01)63534-1 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA ZB163 UT WOS:000072442700006 PM 9507819 ER PT J AU Nelson, JB Kavoussi, LR Walther, MM AF Nelson, JB Kavoussi, LR Walther, MM TI Re: A case of Cushing's syndrome due to adrenocortical carcinoma with recurrence 19 months after laparoscopic adrenalectomy - T. Ushiyama, K. Suzuki, S. Kageyama, K. Fujita, Y. Oki and T. Yoshimi - J. Urol., 157, 2239, 1997 SO JOURNAL OF UROLOGY LA English DT Letter ID EXPERIENCE C1 Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21224 USA. NIH, Bethesda, MD 20891 USA. RP Nelson, JB (reprint author), Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, 4940 Eastern Ave, Baltimore, MD 21224 USA. NR 8 TC 2 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD APR PY 1998 VL 159 IS 4 BP 1310 EP 1310 DI 10.1016/S0022-5347(01)63596-1 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA ZB163 UT WOS:000072442700068 PM 9507868 ER PT J AU Chun, RF Semmes, OJ Neuveut, C Jeang, KT AF Chun, RF Semmes, OJ Neuveut, C Jeang, KT TI Modulation of Sp1 phosphorylation by human immunodeficiency virus type 1 Tat SO JOURNAL OF VIROLOGY LA English DT Review ID RNA-POLYMERASE-II; DEPENDENT PROTEIN-KINASE; LONG TERMINAL REPEAT; NF-KAPPA-B; DNA-BINDING ACTIVITY; CELLULAR TRANSCRIPTION FACTOR; HIV-1 TAT; IN-VITRO; ACTIVATED TRANSCRIPTION; SYNERGISTIC ACTIVATION AB We previously reported (K.T. Jeang, R. Chun, N. H. Lin, A. Gatignol, C. G. Glabe, and H. Fan, J. Virol. 67: 6224-6233, 1993) that human immunodeficiency virus type 1 (HIV-1) Tat and Sp1 form a protein-protein complex. Here, we have characterized the physical interaction and a functional consequence of Tat-Sp1 contact. Using in vitro protein chromatography, we mapped the region in Tat that contacts Sp1 to amino acids 30 to 55. We found that in cell-free reactions, Tat augmented double-stranded DNA-dependent protein kinase (DNA-PK)-mediated Sp1 phosphorylation in a contact-dependent manner. Tat mutants that do not bind Sp1 failed to influence phosphorylation of the latter. In complementary experiments, we also found that Tat forms protein-protein contacts with DNA-PK. We confirmed that in HeLa and Jurkat cells, Tat expression indeed increased the intracellular amount of phosphorylated Sp1 in a manner consistent with the results of cell-free assays. Furthermore, using two phosphatase inhibitors and a kinase inhibitor, we demonstrated a modulation of reporter gene expression as a consequence of changes in Sp1 phosphorylation. Taken together, these findings suggest that activity at the HIV-1 promoter is influenced by phosphorylation of Sp1 which is affected by Tat and DNA-PK. C1 NIAID, Mol Microbiol Lab, Mol Virol Sect, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIAID, Mol Microbiol Lab, Mol Virol Sect, Bldg 4,Room 306,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kjeang@atlas.niaid.nih.gov RI Jeang, Kuan-Teh/A-2424-2008; Chun, Rene/A-9415-2010 OI Chun, Rene/0000-0002-0190-0807 NR 114 TC 126 Z9 126 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1998 VL 72 IS 4 BP 2615 EP 2629 PG 15 WC Virology SC Virology GA ZC506 UT WOS:000072586900006 PM 9525578 ER PT J AU Lekstrom-Himes, JA Pesnicak, L Straus, SE AF Lekstrom-Himes, JA Pesnicak, L Straus, SE TI The quantity of latent viral DNA correlates with the relative rates at which herpes simplex virus types 1 and 2 cause recurrent genital herpes outbreaks SO JOURNAL OF VIROLOGY LA English DT Article ID GUINEA-PIGS; INDUCED REACTIVATION; INFECTION; TRANSCRIPT; EXPRESSION; GANGLIA; SITE AB Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) hare evolved specific anatomic tropisms and site-dependent rates of reactivation, To determine whether reactivation rates depend on distinct abilities of HSV-1 and -2 to establish latency and to express latency-associated transcripts (LATs), virulent strains of each virus were studied in the guinea pig genital model, Following infection with equivalent titers of virus, the quantities of latent HSV-2 genomes and LATs were higher in lumbosacral ganglia, and HSV-2 infections recurred more frequently and lasted longer than HSV-1 infections, In contrast, if the inoculum of HSV-1 was 10 times that of HSV-2, the quantity of HSV-1 DNA and LATs increased correspondingly and HSV-1 infections were as likely to recur as those with HSV-2, The quantity of latent virus DNA correlates with and may be a major determinant of the site-specific patterns and rates of reactivation of HSV-1 and -2. C1 NIAID, Clin Invest Lab, Med Virol Sect, NIH, Bethesda, MD 20892 USA. RP Straus, SE (reprint author), NIAID, Clin Invest Lab, Med Virol Sect, NIH, Bldg 10,Room 11N228,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 23 TC 58 Z9 59 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1998 VL 72 IS 4 BP 2760 EP 2764 PG 5 WC Virology SC Virology GA ZC506 UT WOS:000072586900023 PM 9525595 ER PT J AU Platt, EJ Wehrly, K Kuhmann, SE Chesebro, B Kabat, D AF Platt, EJ Wehrly, K Kuhmann, SE Chesebro, B Kabat, D TI Effects of CCR5 and CD4 cell surface concentrations on infections by macrophagetropic isolates of human immunodeficiency virus type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; HIV-1 INFECTION; ENVELOPE GLYCOPROTEIN; T-CELLS; RECEPTOR; GENE; EXPRESSION; ENTRY; AIDS; MIP-1-ALPHA AB It has been proposed that changes in cell surface concentrations of coreceptors may control infections by human immunodeficiency virus type 1 (HIV-1), but the mechanisms of coreceptor function and the concentration dependencies of their activities are unknown. To study these issues and to generate stable clones of adherent cells able to efficiently titer diverse isolates of HIV-1, we generated two panels of HeLa-CD4/CCR5 cells in which individual clones express either large or small quantities of CD 1 and distinct amounts of CCR5. The panels were made by transducing parental HeLa-CD4 cells with the retroviral vector SFF-CCR5. Derivative clones expressed a wide range of CCR5 quantities which were between 7.0 x 10(2) and 1.3 x 10(5) molecules/cell as measured by binding antibodies specific for CCR5 and the chemokine [I-125]MIP1 beta. CCR5 was mobile in the membranes, as indicated by antibody-induced patching. In cells with a large amount of CD4, an unexpectedly low trace of CCR5 (between 7 x 10(2) and 2.0 x 10(3) molecules/cell) was sufficient for maximal susceptibility to all tested HN-1, including primary patient macrophagetropic and T-cell-tropic isolates. Indeed, the titers as indicated by immunoperoxidase staining of infected foci were as high as the tissue culture infectious doses measured in human peripheral blood mononuclear cells. In contrast, cells with a small amount of CD4 required a much larger quantity of CCR5 for maximal infection by macrophagetropic HIV-1 (ca. 1.0 x 10(4) to 2.0 x 10(4) molecules/cell). Cells that expressed low and high amounts of CD4 were infected with equal efficiencies when CCR5 concentrations were above threshold levels for maximal infection. Our results suggest that the concentrations of CD4 and CCR5 required for efficient infections by macrophagetropic HIV-I are interdependent and that the requirements for each are increased when the other component is present in a limiting amount. We conclude that CD4 and CCR5 directly or indirectly interact in a concentration-dependent manner within a pathway that is essential for infection by macrophagetropic HIV-1. In addition, our results suggest that multivalent virus-receptor bonds and diffusion in the membrane contribute to HIV-1 infections. C1 Oregon Hlth Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97201 USA. NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Kabat, D (reprint author), Oregon Hlth Sci Univ, Dept Biochem & Mol Biol, L224,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. FU NCI NIH HHS [R56 CA067358, CA67358, R01 CA067358]; NIAID NIH HHS [IF32AID9735] NR 75 TC 749 Z9 756 U1 3 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1998 VL 72 IS 4 BP 2855 EP 2864 PG 10 WC Virology SC Virology GA ZC506 UT WOS:000072586900033 PM 9525605 ER PT J AU Rezende, LF Curr, K Ueno, T Mitsuya, H Prasad, VR AF Rezende, LF Curr, K Ueno, T Mitsuya, H Prasad, VR TI The impact of multidideoxynucleoside resistance-conferring mutations in human immunodeficiency virus type 1 reverse transcriptase on polymerase fidelity and error specificity SO JOURNAL OF VIROLOGY LA English DT Article ID COMBINATION THERAPY; TEMPLATE-PRIMER; DNA-SYNTHESIS; HIV-1; MECHANISM; TERMINATION; REPLICATION; ZIDOVUDINE; DIDANOSINE; INFECTION AB Variants of human immunodeficiency virus type 1 (HIV-1) that are highly resistant to a number of nucleoside analog drugs have been shown to develop in some patients receiving 2',3'-dideoxy-3'-azidothymidine therapy. in combination with 2',3'-dideoxycytidine or 2',3'-dideoxyinosine. The appearance, in the reverse transcriptase (RT), of the Q151M mutation in such variants precedes the sequential appearance of three or four additional mutations, resulting in a highly resistant virus, Three of the affected residues are proposed to lie in the vicinity of the template-primer in the three-dimensional structure of the HIV-1 RT-double-stranded DNA complex. The amino acid residue Q151 is thought to be very near the templating base, The nucleoside analog resistance mutations in the beta 9-beta 10 (M184V) and the beta 5a (E89G) strands of HIV-1 RT were previously shown to increase the fidelity of deoxynucleoside triphosphate insertion, Therefore, we have examined wild-type HIV-1(BH10) RT and two nucleoside analog-resistant variants, the Q151M and A62V/V75I/F77L/F116Y/Q151M (VILYM) RTs, for their overall forward mutation rates in an M13 gapped-duplex assay that utilizes [lacZ alpha as a reporter, The overall error rates for the wild-type, the Q151M, and the VILYM RTs were 4.5 x 10(-5), 4.0 x 10(-5), and 2.3 x 10(-5) per nucleotide, respectively, Although the mutant RTs displayed minimal decreases in the overall error rates compared to wild-type RT, the error specificities of both mutant RTs were altered, The Q151M RT mutant generated new hot spots, which were not observed for wild-type HIV-1 RT previously, The VILYM RT showed a marked reduction in error rate at two of the predominant mutational hot spots that have been observed for wild-type HIV-1 RT. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. NCI, Expt Retrovirol Sect, NIH, Bethesda, MD 20892 USA. RP Prasad, VR (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. RI Ueno, Takamasa/F-5788-2013 OI Ueno, Takamasa/0000-0003-4852-4236 FU NIAID NIH HHS [AI-30861, AI40375, R01 AI030861, R21 AI030861, R37 AI030861]; NIGMS NIH HHS [T32 GM007491, T32-GM07491] NR 37 TC 44 Z9 44 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1998 VL 72 IS 4 BP 2890 EP 2895 PG 6 WC Virology SC Virology GA ZC506 UT WOS:000072586900037 PM 9525609 ER PT J AU Tao, T Durbin, AP Whitehead, SS Davoodi, F Collins, PL Murphy, BR AF Tao, T Durbin, AP Whitehead, SS Davoodi, F Collins, PL Murphy, BR TI Recovery of a fully viable chimeric human parainfluenza virus (PIV) type 3 in which the hemagglutinin-neuraminidase and fusion glycoproteins have been replaced by those of PIV type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; VESICULAR STOMATITIS-VIRUS; PARA-INFLUENZA; SEQUENCE-ANALYSIS; GENE-EXPRESSION; CLONED CDNA; RNA; PARAMYXOVIRUS; REPLICATION; VACCINE AB The recent recovery of human parainfluenza virus type 3 (PIV3) from cDNA, together with the availability of a promising, highly characterized live attenuated PIV3 vaccine virus, suggested a novel strategy for the rapid development of comparable recombinant vaccine viruses for human PIV1 and PIV2. The strategy, illustrated here for PIV1, is to create chimeric viruses in which the two protective antigens, the hemagglutinin-neuraminidase (HN) and fusion (F) envelope glycoproteins, of an attenuated PIV3 variant are replaced by those of PIV1 or PIV2. As a first step, this has been achieved by using recombinant wild-type (wt) PIV3 as the recipient for PIV1 HN and F, engineered so that each PIV1 open reading frame is flanked by the existing PIV3 nontranslated regions and transcription signals. This yielded a viable chimeric recombinant virus, designated rPIV3-1, that encodes the PIV1 HN and F glycoproteins in the background of the wt PIV3 internal proteins. There were three noteworthy findings. First, in contrast to recently reported glycoprotein replacement chimeras of vesicular somatitis virus or measles virus, the PIV3-1 chimera replicates in LLC-MK2 cells and in the respiratory tract of hamsters as efficiently as its PIV1 and PIV3 parents. This is remarkable because the HN and F glycoproteins share only 43 and 47%, respectively, overall amino acid sequence identity between serotypes. In particular, the cytoplasmic tails share only 9 to 11% identity, suggesting that their presumed role in virion morphogenesis does not involve sequence-specific contacts. Second, rPIV3-1 was found to possess biological properties derived from each of its parent viruses. Specifically, it requires trypsin for efficient plaque formation in tissue culture, like its PIV1 parent but unlike PIV3. On the other hand, it causes an extensive cytopathic effect (CPE) in LLC-MK2 cultures which resembles that of its PIV3 parent but differs from that of its noncytopathic PIV1 parent. This latter Ending indicates that the genetic basis for the CPE of PIV3 in tissue culture lies outside regions encoding the HN or F glycoprotein. Third, it should now be possible to rapidly develop a live attenuated PIV1 vaccine by the staged introduction of known, characterized attenuating mutations present in a live attenuated PIV3 vaccine candidate into the PIV3-1 cDNA followed by recovery of attenuated derivatives of rPIV3-1. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Tao, T (reprint author), NIAID, Infect Dis Lab, NIH, 7 Ctr Dr,MSC 0720, Bethesda, MD 20892 USA. NR 38 TC 50 Z9 50 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1998 VL 72 IS 4 BP 2955 EP 2961 PG 7 WC Virology SC Virology GA ZC506 UT WOS:000072586900044 PM 9525616 ER PT J AU Ott, DE Coren, LV Copeland, TD Kane, BP Johnson, DG Sowder, RC Yoshinaka, Y Oroszlan, S Arthur, LO Henderson, LE AF Ott, DE Coren, LV Copeland, TD Kane, BP Johnson, DG Sowder, RC Yoshinaka, Y Oroszlan, S Arthur, LO Henderson, LE TI Ubiquitin is covalently attached to the p6(Gag) proteins of human immunodeficiency virus type 1 and simian immunodeficiency virus and to the p12(Gag) protein of Moloney murine leukemia virus SO JOURNAL OF VIROLOGY LA English DT Article ID PROTEOLYTIC PATHWAY; CELLULAR PROTEINS; GAG PROTEINS; MN STRAIN; DEGRADATION; PROTEASOME; PARTICLES; RELEASE; VIRIONS; ALPHA AB Host proteins are incorporated into retroviral virions during assembly and budding, We have examined three retroviruses, human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus (SIV), and Moloney murine leukemia virus (Mo-MuLV), for the presence of ubiquitin inside each of these virions. After a protease treatment to remove exterior viral as well as contaminating cellular proteins, the proteins remaining inside the virion were analyzed, The results presented here show that all three virions incorporate ubiquitin molecules at approximately 10% of the level of Gag found in virions. In addition to free ubiquitin, covalent ubiquitin-Gag complexes were detected, isolated, and characterized from all three viruses. Our immunoblot and protein sequencing results on treated virions showed that approximately 2% of either HIV-1 or SIV p6(Gag) was covalently attached to a single ubiquitin molecule inside the respective,virions and that approximately 2 to 5% of the p12(Gag) in Mo-MuLV virions was monoubiquitinated. These results show that ubiquitination of Gag is conserved among these retroviruses and occurs in the p6(Gag) portion of the Gag polyprotein, a region that is likely to be involved in assembly and budding. C1 NCI, AIDS Vaccine Program, SAIC, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Ott, DE (reprint author), NCI, AIDS Vaccine Program, SAIC, Frederick Canc Res & Dev Ctr, POB B, Frederick, MD 21702 USA. EM ott@avpvx1.ncifcrf.gov NR 42 TC 129 Z9 133 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1998 VL 72 IS 4 BP 2962 EP 2968 PG 7 WC Virology SC Virology GA ZC506 UT WOS:000072586900045 PM 9525617 ER PT J AU Sosnovtsev, SV Sosnovtseva, SA Green, KY AF Sosnovtsev, SV Sosnovtseva, SA Green, KY TI Cleavage of the feline calicivirus capsid precursor is mediated by a virus-encoded proteinase SO JOURNAL OF VIROLOGY LA English DT Article ID HEMORRHAGIC-DISEASE VIRUS; INFECTED-CELLS; 3C-LIKE PROTEASE; NUCLEOTIDE-SEQUENCE; RNA; POLYPROTEIN; GENOME; IDENTIFICATION; POLYPEPTIDE; EXPRESSION AB Feline calicivirus (FCV), a member of the Caliciviridae, produces its major structural protein as a precursor polyprotein from a subgenomic-sized mRNA, In this study, we show that the proteinase responsible for processing this precursor into the mature capsid protein is encoded by the viral genome at the 3'-terminal portion of open reading frame 1 (ORF1), Protein expression studies of either the entire or partial ORF1 indicate that the proteinase is active when expressed either in in vitro translation or in bacterial cells. Site-directed mutagenesis was used to characterize the proteinase Glu-Ala cleavage site in the capsid precursor, utilizing an in vitro cleavage assay in which mutant precursor proteins translated from cDNA clones were used as substrates for trans cleavage by the proteinase, In general, amino acid substitutions in the P1 position (Glu) of the cleavage site were less well tolerated by the proteinase than those in the P1' position (Ala). The precursor cleavage site mutations were introduced into an infectious cDNA clone of the FCV genome, and transfection of RNA derived from these clones into feline kidney cells showed that efficient cleavage of the capsid precursor by the virus-encoded proteinase is a critical determinant in the growth of the virus. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Green, KY (reprint author), 9000 Rockville Pike,Bldg 7,Room 137, Bethesda, MD 20892 USA. NR 33 TC 82 Z9 85 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1998 VL 72 IS 4 BP 3051 EP 3059 PG 9 WC Virology SC Virology GA ZC506 UT WOS:000072586900056 PM 9525628 ER PT J AU Moriuchi, H Moriuchi, M Fauci, AS AF Moriuchi, H Moriuchi, M Fauci, AS TI Differentiation of promonocytic U937 subclones into macrophagelike phenotypes regulates a cellular factor(s) which modulates fusion/entry of macrophagetropic human immunodeficiency virus type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 ENTRY; MONONUCLEAR PHAGOCYTES; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; INFECTION; RECEPTOR; TROPISM; MIP-1-ALPHA; MIP-1-BETA; RANTES AB Monocytes/macrophages (M/M) and CD4(+) T cells are two important targets of human immunodeficiency virus (HIV) infection. Different strains of HIV-1 vary markedly in their abilities to infect cells belonging to the M/M lineage, macrophagetropic (M-tropic) HIV-1 strains replicate well in primary lymphocytes as well as in primary macrophages; however, they generally infect T cell lines poorly, if at all. Although promonocyte cell lines such as U937 have been used as in vitro models of HIV-1 infection of M/M, these cell lines are susceptible to certain T-cell-tropic (T-tropic) HIV-1 strains but are resistant to M-tropic HIV-1. In this study, we demonstrate that (i) certain U937 clones ("plus" clones), which are susceptible only to T-tropic HIV-1, became highly susceptible to M-tropic HIV-1 upon differentiation with retinoic acid (RA); (ii) other U937 clones ("minus" clones), which are resistant to both T- and M-tropic HIV-1, remain resistant to both viruses; and (iii) RA treatment induces expression of CCR5, a fusion/entry cofactor for M-tropic HIV-1 in both types of U937 clones, and yet enhances the fusogenicity of the plus clones, but not the minus clones, with M-tropic Env's. These results indicate that the major restriction of M-tropic HIV-1 infection in promonocytic cells occurs at the fusion/entry level, that differentiation into macrophage-like phenotypes renders some of these cells highly susceptible to infection with M-tropic HIV-1, and that CD4 and CCR5 may not be the only determinants of fusion/entry of M-tropic HIV-1 in these cells. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Moriuchi, H (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 6A11, Bethesda, MD 20892 USA. EM hmoriuchi@atlas.niaid.nih.gov NR 43 TC 20 Z9 20 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1998 VL 72 IS 4 BP 3394 EP 3400 PG 7 WC Virology SC Virology GA ZC506 UT WOS:000072586900098 PM 9525669 ER PT J AU Tanaka, A Oka, K Tanaka, K Jinno, A Ruscetti, SK Kai, K AF Tanaka, A Oka, K Tanaka, K Jinno, A Ruscetti, SK Kai, K TI The entire nucleotide sequence of friend-related and paralysis-inducing PVC-441 murine leukemia virus (MuLV) and its comparison with those of PVC-211 MuLV and friend MuLV SO JOURNAL OF VIROLOGY LA English DT Article ID ENDOTHELIAL-CELL TROPISM; NEUROPATHOGENIC VARIANT; MICE AB PVC-441 murine leukemia virus (MuLV) is a member of the PVC group of Friend MuLV (F-MuLV)-derived neuropathogenic retroviruses. In order to determine the molecular basis for the difference in neuropathogenicity between PVC-441 and the previously characterized PVC-211 MuLVs, the entire nucleotide sequence of PVC-441 MuLV was determined and compared with those of PVC-211 and F-MuLV. The results suggest that PVC-441 and PVC-211 MuLVs were formed as a result of random mutations of F-MuLV and developed differently. The distinct pathogenicities of PVC-441 and PVC-211 MuLVs were maintained in the viruses regenerated from their molecular clones, and the sequences responsible for the pathological differences observed can be localized to the env gene. The amino acid sequence of PVC-441 deduced from its nucleotide sequence revealed a number of differences from PVC-211, the most striking of which was a difference at position 129 of the SU proteins in the two viruses. Host range studies with a brain capillary endothelial cell line (RTEC-6) and Chinese hamster ovary cells (CHO-K1) revealed that PVC-441. Like PVC-211, could infect these cells but its efficiency of infection was lower than that of PVC-211. These results may account for the difference in neuropathogenicity between PVC-441 and PVC-211. C1 Yamaguchi Univ, Fac Agr, Dept Vet Microbiol, Yamaguchi 753, Japan. NCI, Basic Res Lab, Frederick, MD 21702 USA. RP Kai, K (reprint author), Yamaguchi Univ, Fac Agr, Dept Vet Microbiol, Yamaguchi 753, Japan. NR 12 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1998 VL 72 IS 4 BP 3423 EP 3426 PG 4 WC Virology SC Virology GA ZC506 UT WOS:000072586900103 PM 9525674 ER PT J AU Rein, A Yang, CL Haynes, JA Mirro, J Compans, RW AF Rein, A Yang, CL Haynes, JA Mirro, J Compans, RW TI Evidence for cooperation between murine leukemia virus Env molecules in mixed oligomers SO JOURNAL OF VIROLOGY LA English DT Article ID PFIZER MONKEY VIRUS; CYTOPLASMIC DOMAIN; ENVELOPE PROTEIN; FUSION ACTIVITY; TRANSMEMBRANE GLYCOPROTEIN; INFLUENZA HEMAGGLUTININ; MEMBRANE-FUSION; CELL-FUSION; RETROVIRUS; CLEAVAGE AB A retroviral Env molecule consists of a surface glycoprotein (SU) complexed with a transmembrane protein (TM). In turn, these complexes are grouped into oligomers on the surfaces of the cell and of the virion. In the case of murine leukemia viruses (MuLVs), the SU moieties are polymorphic, with SU proteins of different viral isolates directed towards different cell surface receptors. During maturation of the released virus particle, the 16 C-terminal residues of TM (the R peptide or p2E) are removed from the protein by the viral protease; this cleavage is believed to activate the membrane-fusing potential of MuLV Env. We have tested the possibility that different MuLV Env proteins in the same cell can interact with each other, both physically and functionally in mixed oligomers. We found that coexpressed Env molecules can be precipitated out of cell lysates by antiserum which reacts with only one of them. Furthermore, they can evidently cooperate with each other: if one Env species lacks the R peptide, then it can apparently induce fusion if the SU protein of the other Env species encounters its cognate receptor on the surface of another cell. This functional interaction between different Env molecules has a number of implications with respect to the mechanism of induction of membrane fusion, for the genetic analysis of Env function, and for the design of targeted retroviral vectors for gene therapy. C1 NCI, Retroviral Genet Sect, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. RP Rein, A (reprint author), NCI, Retroviral Genet Sect, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, POB B,Bldg 535,Rm 211, Frederick, MD 21702 USA. EM rein@ncifcrf.gov RI Compans, Richard/I-4087-2013; Yang, Chinglai/D-1409-2014 OI Compans, Richard/0000-0003-2360-335X; Yang, Chinglai/0000-0002-9308-7760 FU NCI NIH HHS [CA18611] NR 35 TC 29 Z9 29 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD APR PY 1998 VL 72 IS 4 BP 3432 EP 3435 PG 4 WC Virology SC Virology GA ZC506 UT WOS:000072586900105 PM 9525676 ER PT J AU McPherson, C AF McPherson, C TI Cost-ly error SO LAB ANIMAL LA English DT Letter C1 NIH, Comm Revis Cost Anal & Rate Setting Man Anim Res, Bethesda, MD 20892 USA. RP McPherson, C (reprint author), NIH, Comm Revis Cost Anal & Rate Setting Man Anim Res, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD APR PY 1998 VL 27 IS 4 BP 14 EP 14 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA ZG078 UT WOS:000072963400002 ER PT J AU Feinstein, L Miller, GF Penney, BE AF Feinstein, L Miller, GF Penney, BE TI Diagnostic exercise: Lethal pneumonia in neonatal kittens SO LABORATORY ANIMAL SCIENCE LA English DT Article ID POLYMERASE CHAIN-REACTION; FELINE C1 NIH, Natl Ctr Res Resources, Vet Resources Program, Bethesda, MD 20892 USA. RP Feinstein, L (reprint author), NIH, Natl Ctr Res Resources, Vet Resources Program, Bethesda, MD 20892 USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 USA SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD APR PY 1998 VL 48 IS 2 BP 190 EP 192 PG 3 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 109KF UT WOS:000075321000011 PM 10090012 ER PT J AU Weigler, BJ Wiltron, LA Hancock, SI Thigpen, JE Goelz, MF Forsythe, DB AF Weigler, BJ Wiltron, LA Hancock, SI Thigpen, JE Goelz, MF Forsythe, DB TI Further evaluation of a diagnostic polymerase chain reaction assay for Pasteurella pneumotropica SO LABORATORY ANIMAL SCIENCE LA English DT Article ID MICE; RODENTS; UREAE C1 NIEHS, Comparat Med Branch, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Coll Vet Med, Dept Compan Anim & Special Species Med, Raleigh, NC USA. RP Goelz, MF (reprint author), NIEHS, Comparat Med Branch, MD C1-06, Res Triangle Pk, NC 27709 USA. NR 22 TC 13 Z9 13 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 USA SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD APR PY 1998 VL 48 IS 2 BP 193 EP 196 PG 4 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 109KF UT WOS:000075321000012 PM 10090013 ER PT J AU Hu, JJ Pope, M Brown, C O'Doherty, U Miller, CJ AF Hu, JJ Pope, M Brown, C O'Doherty, U Miller, CJ TI Immunophenotypic characterization of simian immunodeficiency virus-infected dendritic cells in cervix, vagina, and draining lymph nodes of rhesus monkeys SO LABORATORY INVESTIGATION LA English DT Article ID MEMORY T-LYMPHOCYTES; LANGERHANS CELLS; GENITAL-TRACT; HETEROSEXUAL TRANSMISSION; INTRAVAGINAL INOCULATION; INTERDIGITATING CELLS; MIGRATION PATTERNS; VEILED CELLS; HUMAN SKIN; MACAQUES AB Significant progress has been made in understanding the biology of heterosexual transmission of HIV by utilizing the simian immunodeficiency virus (SIV)/rhesus monkey animal model. Our previous studies have shown that SIV-infected cells within the stratified squamous epithelium of the vagina have a dendritic morphology. However, the type of cell infected was not conclusively determined. The purpose of the present study was to immunophenotype the SIV-infected cells in the lower reproductive tract and genital lymph nodes of the female rhesus monkey. Vagina, cervix, and iliac lymph node from eight chronically SIV-infected adult female monkeys were examined for this study. None of the animals had histologic evidence of opportunistic infections or genital tract pathogens other than SIV. Combined in situ hybridization and immunohistochemistry were used to detect SIV RNA and to determine the immunophenotype of SIV-infected cells in tissue sections and cytospin preparations of cells from the tissues. We now show that SIV-infected cells were most common in iliac lymph node and that the majority of infected cells in the lymph node were T lymphocytes. SIV-infected macrophages, Langerhans' cells, and dendritic cells were also found in the lymph node. SIV-infected cells were found within the epithelium and lamina propria of the vagina. Although most of the infected cells were T cells, a significant proportion (approximately 40%) of the SIV-infected cells in cytospin preparations from explant cultures of vagina and cervix were Langerhans' cells. SIV-infected T cells in the lower genital tract were commonly associated with focal mononuclear cell infiltrates. SIV-infected macrophages were rarely found in the genital tract. The present study provides the first direct demonstration that Langerhans' cells and dendritic cells in the genital tract and lymph nodes are infected with SIV in vivo. Thus, dendritic cells, in general, and Langerhans' cells, in particular, are important reservoirs for HIV/SIV replication in vivo. C1 Univ Calif Davis, Sch Vet Med, Calif Reg Primate Res Ctr, Virol & Immunol Unit, Davis, CA 95616 USA. Univ Calif Davis, Sch Vet Med, Ctr Comparat Med, Davis, CA 95616 USA. Univ Calif Davis, Sch Vet Med, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA. Rockefeller Univ, Cellular Physiol & Immunol Lab, New York, NY 10021 USA. NIAID, Immunodeficiency Viruses Sect, Infect Dis Lab, Bethesda, MD 20892 USA. Hosp Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Miller, CJ (reprint author), Univ Calif Davis, Sch Vet Med, Calif Reg Primate Res Ctr, Virol & Immunol Unit, Davis, CA 95616 USA. FU NCRR NIH HHS [NCRR00169]; NIAID NIH HHS [AI39435, AI40877] NR 66 TC 65 Z9 66 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD APR PY 1998 VL 78 IS 4 BP 435 EP 451 PG 17 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA ZH996 UT WOS:000073169200007 PM 9564888 ER PT J AU Haas, OA Henn, T Romanakis, K du Manoir, S Lengauer, C AF Haas, OA Henn, T Romanakis, K du Manoir, S Lengauer, C TI Comparative genomic hybridization as part of a new diagnostic strategy in childhood hyperdiploid acute lymphoblastic leukemia SO LEUKEMIA LA English DT Article DE hyperdiploid ALL; flow cytometry; cytogenetics; fluorescence in situ hybridization (FISH); comparative genomic hybridization (CGH) ID PEDIATRIC-ONCOLOGY-GROUP; FLUORESCENCE INSITU HYBRIDIZATION; IN-SITU HYBRIDIZATION; CYTOGENETIC ABNORMALITIES; INTERPHASE CYTOGENETICS; HUMAN-CHROMOSOMES; FLOW-CYTOMETRY; SOLID TUMORS; DNA; CHILDREN AB The detailed definition of karyotype changes associated with hyperdiploid acute lymphoblastic leukemia (ALL) is a precondition for their exploitation in minimal residual disease studies with fluorescence in situ hybridization analysis (FISH). In addition, certain karyotype patterns may have different prognostic implications. We have therefore used comparative genomic hybridization (CGH) to analyze the quantitative karyotype abnormalities in 14 cases of hyperdiploid ALL and correlated the results with those obtained by flow cytometry and conventional cytogenetic analyses. Despite an overall good agreement between the karyotypes obtained by classical banding techniques and CGH, we came across at least one karyotype discrepancy per case. Clarification of the discordant findings with fluorescence in situ hybridization (FISH) showed that all stem lines had been correctly defined by CGH. In eight cases, however, cytogenetic analyses revealed structural abnormalities that were undetectable by CGH. The other discrepancies were mainly due to a cytogenetic misinterpretation of similar sized and shaped chromosomes. Based on these findings we present a new diagnostic strategy for childhood ALL that includes flow cytometry and classical cytogenetics as well as CGH for the analysis of aneuploid cases and FISH to resolve the unavoidable discrepancies. C1 St Anna Childrens Hosp, Childrens Canc Res Inst, A-1090 Vienna, Austria. Univ Kaiserslautern, Inst Human Genet, Kaiserslautern, Germany. NIH, Natl Ctr Human Genome Res, Gene Technol Branch, Bethesda, MD 20892 USA. Johns Hopkins Oncol Ctr, Genet Mol Lab, Baltimore, MD USA. RP Haas, OA (reprint author), St Anna Childrens Hosp, Childrens Canc Res Inst, Kinderspitalgasse 6, A-1090 Vienna, Austria. NR 31 TC 20 Z9 20 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD APR PY 1998 VL 12 IS 4 BP 474 EP 481 DI 10.1038/sj.leu.2400943 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA ZK050 UT WOS:000073279900004 PM 9557603 ER PT J AU Pemrick, SM Abarzua, P Kratzeisen, C Marks, MS Medin, JA Ozato, K Grippo, JF AF Pemrick, SM Abarzua, P Kratzeisen, C Marks, MS Medin, JA Ozato, K Grippo, JF TI Characterization of the chimeric retinoic acid receptor RAR alpha/VDR SO LEUKEMIA LA English DT Article DE retinoic acid receptors (RARs) and chimeras; all-trans retinoic acid; vitamin D-3; permanent gene transfection and expression; terminal differentiation; leukemia ID ACUTE PROMYELOCYTIC LEUKEMIA; NUCLEAR HORMONE RECEPTORS; THYROID-HORMONE; TRANSCRIPTIONAL ACTIVATION; MONOCYTIC DIFFERENTIATION; RESPONSIVE ELEMENT; BINDING-SITE; MAMMALIAN-CELLS; RXR-ALPHA; F9 CELLS AB The chimeric receptor, RAR alpha/VDR, contains the DNA-binding domain of the retinoic acid receptor (RAR alpha) and the ligand-binding domain of the vitamin D receptor (VDR), The ligand-binding properties of RAR alpha/VDR are equivalent to that of VDR, with an observed K-d for 1 alpha,25 dihydroxy-vitamin D-3 (D-3) of 0.5 nM. In CV-1 cells. both RAR alpha and RAR alpha/VDR induce comparable levels of ligand-mediated transcriptional activity from the retinoic acid responsive reporter gene, beta(RARE)(3)-TK-luciferase, in the presence of the ligand predicted from the receptor ligand-binding domain. Two chimeric RAR receptors were constructed which contained the ligand-binding domain of the estrogen receptor (ER): RAR alpha/ER and ER/RAR alpha/ER. Both RAR alpha/ER and ER/RAR alpha/ER bind beta-estradiol with high affinity, and are transcriptionally active only from palindromic RAREs (TREpal and/or (TRE3)(3)). Only RAR alpha/VDR matched in kind and degree the functional characteristics of RAR alpha: (1) maximally active from the beta(RARE); (2) moderately active from the TREs; (3) inactive from the retinoic X receptor response elements (RXREs) ApoA1 and CRBP II; (4) forms heterodimers with RXR alpha; and (5) binds to the beta RARE. F9 embryonal carcinoma cell lines were generated which express RAR alpha/VDR mRNA (F9-RAR alpha/VDR cells) and compared with F9 wild-type (FS-Wt) cells, which do not express VDR mRNA. Treatment with all-trans retinoic acid (tRA) inhibits cell growth and induces the differentiation morphology in both FS-Wt and F9-RAR alpha/VDR cells; whereas, treatment with D-3 is similarly effective only for F9-RAR alpha/VDR cells. It is concluded RAR alpha/VDR is an useful 'tool' to pinpoint, or to augment transcription from RAREs in gene pathways controlled by RAR without inhibiting the retinoid responsiveness of endogenous RARs. C1 Hoffmann La Roche Inc, Dept Metab Dis, Nutley, NJ 07110 USA. Hoffmann La Roche Inc, Dept Oncol, Nutley, NJ 07110 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Pemrick, SM (reprint author), Merck & Co Inc, Merck Sharp & Dohme Res Labs, RY32-605, Rahway, NJ 07065 USA. NR 75 TC 4 Z9 4 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD APR PY 1998 VL 12 IS 4 BP 554 EP 562 DI 10.1038/sj.leu.2400937 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA ZK050 UT WOS:000073279900015 PM 9557614 ER PT J AU Ding, SJ Wolff, SD Epstein, FH AF Ding, SJ Wolff, SD Epstein, FH TI Improved coverage in dynamic contrast-enhanced cardiac MRI using interleaved gradient-echo EPI SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE myocardium; perfusion; first-pass; contrast enhancement ID MYOCARDIAL BLOOD-FLOW; VARIABLE FLIP ANGLES; STEADY-STATE; TRANSVERSE MAGNETIZATION; SNAPSHOT FLASH; PERFUSION; SIGNAL; AMMONIA; DISEASE; HUMANS AB An interleaved gradient-echo echo-planar imaging (IGEPI) sequence was modified for and applied to dynamic contrast-enhanced imaging of the heart. Using IGEPI, images with 3.0 x 3.9 mm nominal in-plane resolution are acquired in 100 ms, enabling eight slices per heartbeat for a heart rate of 60 beats/min. The acquisition speed and use of saturation pre; pulses allows acquisition of short-and long-axis images during the same contrast bolus. IGEPI maintains the acquisition characteristics required for performing a quantitative first-pass perfusion analysis as well as providing improved coverage compared with conventional fast gradient echo. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. Gen Elect Med Syst, Appl Sci Lab, Waukesha, WI USA. RP Ding, SJ (reprint author), NHLBI, Cardiac Energet Lab, NIH, 10 Ctr Dr,MSC 1061,Bldg 10,Room B1D161, Bethesda, MD 20892 USA. NR 34 TC 81 Z9 81 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD APR PY 1998 VL 39 IS 4 BP 514 EP 519 DI 10.1002/mrm.1910390403 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZD581 UT WOS:000072700900002 PM 9543412 ER PT J AU Wine, JJ Glavac, D Hurlock, G Robinson, C Lee, M Potocnik, U Ravnik-Glavac, M Dean, M AF Wine, JJ Glavac, D Hurlock, G Robinson, C Lee, M Potocnik, U Ravnik-Glavac, M Dean, M TI Genomic DNA sequence of Rhesus (M-mulatta) cystic fibrosis (CFTR) gene SO MAMMALIAN GENOME LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; IDENTIFICATION; CLONING; LOCALIZATION; EXPRESSION; DISEASE; HOMOLOG; MICE AB Cystic fibrosis is a common human genetic disease caused by mutations in CFTR, a gene that codes for a chloride channel that is regulated by phosphorylation and cytosolic nucleotides. As part of a program to discover natural animal models for human genetic diseases, we have determined the genomic sequence of CFTR in the Rhesus monkey, Macaca mulatta. The coding region of rhesus CFTR is 98.3% identical to human CFTR at the nucleotide level and 98.2% identical and 99.7% similar at the amino acid level. Partial sequences of flanking introns (5582 base pair positions analyzed) revealed 91.1% identity with human introns. Relative to rhesus intronic sequence, the human sequences had 27 insertions and 22 deletions. Primer sequences for amplification of rhesus genomic CFTR sequences are provided. The accession number is AF013753 (all 27 exons and some flanking intronic sequence). C1 Stanford Univ, Cyst Fibrosis Res Lab, Stanford, CA 94305 USA. Univ Ljubljana, Lab Mol Pathol, Ljubljana, Slovenia. NCI, Human Genet Sect, Lab Genom Divers, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Wine, JJ (reprint author), Stanford Univ, Cyst Fibrosis Res Lab, Bldg 420 Main Quad, Stanford, CA 94305 USA. RI Dean, Michael/G-8172-2012; OI Dean, Michael/0000-0003-2234-0631; Potocnik, Uros/0000-0003-1624-9428 FU NCRR NIH HHS [RR00169]; NHLBI NIH HHS [HL51776] NR 18 TC 11 Z9 12 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD APR PY 1998 VL 9 IS 4 BP 301 EP 305 DI 10.1007/s003359900753 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA ZC877 UT WOS:000072628000007 PM 9530627 ER PT J AU Rooney, RJ Daniels, RR Jenkins, NA Gilbert, DJ Rothammer, K Morris, SW Higgs, DR Copeland, NG AF Rooney, RJ Daniels, RR Jenkins, NA Gilbert, DJ Rothammer, K Morris, SW Higgs, DR Copeland, NG TI Chromosomal location and tissue expression of the gene encoding the adenovirus E1A-regulated transcription factor E4F in humans and mice SO MAMMALIAN GENOME LA English DT Article ID MOUSE GENOME; DISEASE; SEQUENCES; PKD1; E1A; 16P13.3; PROTEIN; REGION; TYPE-1; MAP C1 St Jude Childrens Res Hosp, Dept Biochem, Memphis, TN 38105 USA. St Jude Childrens Res Hosp, Dept Expt Oncol, Memphis, TN 38105 USA. John Radcliffe Hosp, Inst Mol Med, MRC, Mol Haematol Unit, Oxford OX3 9DS, England. NCI, Mammalian Genet Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Univ Tennessee, Coll Med, Dept Pediat, Memphis, TN 38163 USA. RP Rooney, RJ (reprint author), St Jude Childrens Res Hosp, Dept Biochem, 332 N Lauderdale St, Memphis, TN 38105 USA. FU NCI NIH HHS [P30 CA21756] NR 26 TC 12 Z9 14 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD APR PY 1998 VL 9 IS 4 BP 320 EP 323 DI 10.1007/s003359900758 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA ZC877 UT WOS:000072628000012 PM 9530632 ER PT J AU Centanni, JM de Miguel, M Gopalan, G Gilbert, DJ Copeland, NG Jenkins, NA Donovan, PJ AF Centanni, JM de Miguel, M Gopalan, G Gilbert, DJ Copeland, NG Jenkins, NA Donovan, PJ TI Interleukin-1 receptor-associated kinase gene Il1rak maps to the mouse X chromosome SO MAMMALIAN GENOME LA English DT Article ID PROTEIN-KINASE C1 Univ Alcala de Henares, Dept Cell Biol & Genet, Madrid 28871, Spain. RP Donovan, PJ (reprint author), NCI, Mammalian Genet Lab, ABL Basic Res Program, FCRDC, POB B,Bldg 539, Frederick, MD 21702 USA. NR 8 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD APR PY 1998 VL 9 IS 4 BP 340 EP 341 DI 10.1007/s003359900764 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA ZC877 UT WOS:000072628000018 PM 9530638 ER PT J AU Lentini, A Kleinman, HK Mattioli, P Autuori-Pezzoli, V Nicolini, L Pietrini, A Abbruzzese, A Cardinali, M Beninati, S AF Lentini, A Kleinman, HK Mattioli, P Autuori-Pezzoli, V Nicolini, L Pietrini, A Abbruzzese, A Cardinali, M Beninati, S TI Inhibition of melanoma pulmonary metastasis by methylxanthines due to decreased invasion and proliferation SO MELANOMA RESEARCH LA English DT Article DE melanoma cells; methylxanthines; pulmonary metastasis ID ADENYLATE-CYCLASE; CANCER CELLS; TUMOR-CELLS; BINDING; GROWTH AB Theophylline- and caffeine-treated B16-F10 cells exhibited low adhesion to laminin/collagen type IV and reduced invasion through Matrigel in an in vitro assay. In contrast, theobromine appeared ineffective. When young adult C57BL/6 mice were injected intravenously with theophylline-treated B16-F10 cells, the number of surface lung tumours was markedly reduced. Densitometric analyses performed on digitalized microscopic images of histological sections of lung were used to estimate the frequency (number of lung foci; NLF) and the size (average area of metastatic foci; AMF) of the resulting tumour foci. These parameters were correlated to the proliferation (AMF) and invasion (NLF) of melanoma cells in vivo. The data showed a similar theophylline-induced decrease in the AMF and NLF values (71%, P < 0.01). Caffeine treatment produced a more pronounced decrease in the AMF (61%, P < 0.01) than in the NLF (25%, P < 0.01). To our knowledge, this is the first demonstration that theophylline and caffeine possess the capacity to inhibit not only cell proliferation, but also the metastatic behaviour of melanoma cancer cells. (C) 1998 Lippincott-Raven Publishers. C1 Univ Roma Tor Vergata 2, Dept Biol, I-00133 Rome, Italy. NIDR, Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NIDR, Cellular Dev & Oncol Lab, NIH, Bethesda, MD 20892 USA. Univ Naples, Dept Biochem & Biophys, I-80138 Naples, Italy. RP Beninati, S (reprint author), Univ Roma Tor Vergata 2, Dept Biol, Via Ric Sci, I-00133 Rome, Italy. EM beninati@utovrm.it OI Beninati, Simone/0000-0002-2704-0745 NR 20 TC 31 Z9 31 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD APR PY 1998 VL 8 IS 2 BP 131 EP 137 DI 10.1097/00008390-199804000-00005 PG 7 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA ZE907 UT WOS:000072843600005 PM 9610865 ER PT J AU Sauer, B AF Sauer, B TI Inducible gene targeting in mice using the Cre/lox system SO METHODS-A COMPANION TO METHODS IN ENZYMOLOGY LA English DT Article ID SITE-SPECIFIC RECOMBINATION; EMBRYONIC STEM-CELLS; RECYCLING SELECTABLE MARKERS; CRE RECOMBINASE; MAMMALIAN-CELLS; TRANSGENIC MICE; TRANSCRIPTIONAL ACTIVATION; EUKARYOTIC RIBOSOMES; DNA RECOMBINATION; EXPRESSION AB Molecular techniques now allow the design of precise genetic modifications in the mouse. Not only can defined nucleotide changes be engineered into the genome of the mouse, but genetic switches can be designed to target expression or ablation of any gene (for which basic molecular information is available) to any tissue at any defined time. These strategies promise to contribute substantially to an increased understanding of individual gene function in development and pathogenesis. A powerful tool, both for the design of such genetic switches and for speeding the creation of gene-modified animals, is the Cre site-specific DNA recombinase of bacteriophage P1. Precise DNA rearrangements and genetic switches can be efficiently generated in a straightforward manner using Cre recombinase. In conjunction with inducible systems for controlling Cre expression and function, these recombination-based strategies are likely to have a profound impact on developmental biology and the generation of useful animal models of human disease. (C) 1998 Academic Press. C1 NIDDKD, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA. RP Sauer, B (reprint author), NIDDKD, Biochem & Metab Lab, NIH, Bldg 10,Room 9N119, Bethesda, MD 20892 USA. NR 66 TC 448 Z9 467 U1 9 U2 73 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD APR PY 1998 VL 14 IS 4 BP 381 EP 392 DI 10.1006/meth.1998.0593 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZN714 UT WOS:000073674300004 PM 9608509 ER PT J AU Bono, JL Tilly, K Stevenson, B Hogan, D Rosa, P AF Bono, JL Tilly, K Stevenson, B Hogan, D Rosa, P TI Oligopeptide permease in Borrelia burgdorferi: putative peptide-binding components encoded by both chromosomal and plasmid loci SO MICROBIOLOGY-UK LA English DT Article DE oligopeptide permease; oppA; plasmids; Lyme disease; spirochaetes ID INTEGRAL MEMBRANE-COMPONENTS; DEPENDENT TRANSPORT-SYSTEMS; POLYMERASE CHAIN-REACTION; OUTER SURFACE PROTEIN; LYME-DISEASE; SALMONELLA-TYPHIMURIUM; SEX-PHEROMONE; BACILLUS-SUBTILIS; ESCHERICHIA-COLI; MOLECULAR ANALYSIS AB To elucidate the importance of oligopeptide permease for Borrelia burgdorferi, the agent of Lyme disease, a chromosomal locus in B. burgdorferi that encodes homologues of all five subunits of oligopeptide permease has been identified and characterized. B. burgdorferi has multiple copies of the gene encoding the peptide-binding component, OppA; three reside at the chromosomal locus and two are on plasmids. Northern analyses indicate that each oppA gene is independently transcribed, although the three chromosomal oppA genes are also expressed as bi-and tri-cistronic messages. Induction of one of the plasmid-encoded oppA genes was observed following an increase in temperature, which appears to be an important cue for adaptive responses in vivo. The deduced amino acid sequences suggest that all five borrelial OppA homologues are lipoproteins, but the protease-resistance of at least one of them in intact bacteria is inconsistent with outer-surface localization. Insertional inactivation of a plasmid-encoded oppA gene demonstrates that it is not essential for growth in culture. C1 NIAID, Rocky Mt Labs, Microbial Struct & Funct Lab, Hamilton, MT 59840 USA. RP Rosa, P (reprint author), NIAID, Rocky Mt Labs, Microbial Struct & Funct Lab, 903 S 4th St, Hamilton, MT 59840 USA. NR 54 TC 80 Z9 82 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 1350-0872 J9 MICROBIOL-UK JI Microbiology-(UK) PD APR PY 1998 VL 144 BP 1033 EP 1044 PN 4 PG 12 WC Microbiology SC Microbiology GA ZJ169 UT WOS:000073186400024 PM 9579077 ER PT J AU Emanuel, EJ AF Emanuel, EJ TI The future of euthanasia and physician-assisted suicide: Beyond rights talk to informed public policy SO MINNESOTA LAW REVIEW LA English DT Article ID NETHERLANDS; PATIENT; LIFE; END C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Emanuel, EJ (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. NR 35 TC 14 Z9 14 U1 1 U2 1 PU MINN LAW REVIEW FOUND PI MINNEAPOLIS PA 229 19TH AVE SOUTH UNIV MINNESOTA, MINNEAPOLIS, MN 55455 USA SN 0026-5535 J9 MINN LAW REV JI Minn. Law Rev. PD APR PY 1998 VL 82 IS 4 BP 983 EP 1014 PG 32 WC Law SC Government & Law GA ZJ602 UT WOS:000073233200006 PM 11865919 ER PT J AU Singer, SM Yee, J Nash, TE AF Singer, SM Yee, J Nash, TE TI Episomal and integrated maintenance of foreign DNA in Giardia lamblia SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Giardia lamblia; transfection; puromycin; green fluorescent protein; episome; gene replacement ID GREEN FLUORESCENT PROTEIN; SUBUNIT RIBOSOMAL-RNA; STABLE TRANSFECTION; GENE REPLACEMENT; HOMOLOGOUS RECOMBINATION; ENTAMOEBA-HISTOLYTICA; PHYLOGENETIC PLACE; TRYPANOSOMA-BRUCEI; LACKING PROTOZOAN; TOXOPLASMA-GONDII AB Giardia lamblia is an early diverging eukaryote which causes gastrointestinal disease throughout the world. Different subgroups of Giardia have been defined based on several biochemical and genetic criteria. We have developed a method for stably introducing DNA into the nuclei of the parasite using puromycin acetyltransferase (pac) as a dominant selectable marker. Transfected circular DNAs were maintained as episomes in the isolate WE, a representative of one Giardia subgroup. When input DNAs were linearized, integration was observed to occur by homologous recombination producing gene replacements in this isolate. In isolate GS, which represents a different subgroup, both linear and circular transfected DNAs were integrated into the genome by homologous recombination. In GS, linear DNA again produced gene replacements, while circular DNA produced duplicative integration events. The failure of GS to replicate episomes may reflect differences in the structure or recognition of DNA replication origins between these subgoups. A plasmid shuttle vector was also developed for expression of other genes in Giardia lamblia. Utilizing the green fluorescent protein as a reporter gene in the WE isolate, we show that gene expression from this vector correlated with plasmid copy number over a range of two orders of magnitude. Together these tools should greatly enhance our ability to study both the basic biology and the pathogenesis of this ubiquitous parasite. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Singer, SM (reprint author), NIH, Parasit Dis Lab, Bldg 4,Room B1-06,9000 Rockville Pike, Bethesda, MD 20892 USA. EM SSINGER@ATLAS.NIAID.NIH.GOV NR 46 TC 87 Z9 90 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD APR 1 PY 1998 VL 92 IS 1 BP 59 EP 69 DI 10.1016/S0166-6851(97)00225-9 PG 11 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA ZG201 UT WOS:000072977300006 PM 9574910 ER PT J AU Gupta, RP Bing, GY Hong, JS Abou-Donia, MB AF Gupta, RP Bing, GY Hong, JS Abou-Donia, MB TI cDNA cloning and sequencing of Ca2+/calmodulin-dependent protein kinase II alpha subunit and its mRNA expression in diisopropyl phosphorofluoridate (DFP)-treated hen central nervous system SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE brain; CaM kinase II; cDNA library; diisopropyl phosphorofluoridate; mRNA expression; chicken; OPIDN ID INDUCED DELAYED NEUROTOXICITY; CRESYL PHOSPHATE; CYTOSKELETAL PROTEINS; CALMODULIN KINASE; MOLECULAR-CLONING; SCIATIC-NERVE; BRAIN; PHOSPHORYLATION; BINDING; CHICKEN AB Diisopropyl phosphorofluoridate (DFP) produces delayed neurotoxicity, known as organophosphorus ester-induced delayed neurotoxicity (OPIDN), in hen, human, and other sensitive species. A single dose of DFP (1.7 mg/kg, se.) produces first mild ataxia followed by paralysis in 7-14 days in hens. DFP treatment also increases in vitro autophosphorylation of Ca2+ calmodulin-dependent protein kinase II (CaM kinase II) and the phosphorylation of several cytoskeletal proteins in the hen brain. To investigate whether increase in CaM kinase II activity is associated with increased expression of its mRNA, we cloned and sequenced CaM kinase II alpha subunit cDNA, and used it to study CaM kinase II expression in brain regions and spinal cord. Hen CaM kinase II a subunit differs in 7 amino acids from that of rat CaM kinase II Its mRNA occurs predominantly as a 6.7 kb message, which is very close to that of human CaM kinase II alpha subunit. Northern blot analysis showed a transient increase in CaM kinase II alpha subunit mRNA in the cerebellum and spinal cord of DFP-treated chickens. The increase in CaM kinase II mRNA expression is consistent with the previously reported increase in its activity in brain and spinal cord, and its increased expression only in cerebellum and spinal cord, which are sensitive to the Wallerian-type degeneration characteristic of OPIDN, suggests the probable role of this enzyme in delayed neurotoxicity. C1 Duke Univ, Med Ctr, Dept Pharmacol, Durham, NC 27710 USA. NIEHS, Lab Environm Neurosci, NIH, Res Triangle Pk, NC 27709 USA. RP Abou-Donia, MB (reprint author), Duke Univ, Med Ctr, Dept Pharmacol, POB 3813, Durham, NC 27710 USA. RI bing, guoying/F-7084-2012 NR 31 TC 28 Z9 33 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD APR PY 1998 VL 181 IS 1-2 BP 29 EP 39 DI 10.1023/A:1006863705912 PG 11 WC Cell Biology SC Cell Biology GA ZD328 UT WOS:000072674200004 PM 9562239 ER PT J AU Lewis, LK Kirchner, JM Resnick, MA AF Lewis, LK Kirchner, JM Resnick, MA TI Requirement for end-joining and checkpoint functions, but not RAD52-mediated recombination, after EcoRI endonuclease cleavage of Saccharomyces cerevisiae DNA SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DOUBLE-STRAND BREAKS; CELL-CYCLE ARREST; HOMOLOGOUS RECOMBINATION; GENETIC-CONTROL; INTRACHROMOSOMAL RECOMBINATION; ILLEGITIMATE RECOMBINATION; CHROMOSOMAL-ABERRATIONS; MITOTIC RECOMBINATION; ESCHERICHIA-COLI; REPAIR PATHWAYS AB RAD52 and RAD9 are required for the repair of double-strand breaks (DSBs) induced by physical and chemical DNA-damaging agents in Saccharomyces cerevisiae. Analysis of EcoRI endonuclease expression in vivo revealed that, in contrast to DSBs containing damaged or modified termini, chromosomal DSBs retaining complementary ends could be repaired in rad52 mutants and in G(1)-phase Rad(+) cells. Continuous EcoRI-induced scission of chromosomal DNA blocked the growth of rad52 mutants, with most cells arrested in G(2) phase. Surprisingly, rad52 mutants were not more sensitive to EcoRI-induced cell killing than wild-type strains. In contrast, endonuclease expression was lethal in cells deficient in Ku-mediated end joining. Checkpoint defective rad9 mutants did not arrest cell cycling and lost viability rapidly when EcoRI was expressed. Synthesis of the endonuclease produced extensive breakage of nuclear DNA and stimulated interchromosomal recombination. These results and those of additional experiments indicate that cohesive ended DSBs in chromosomal DNA can be accurately repaired by RAD52-mediated recombination and by recombination-independent complementary end joining in yeast cells. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP NIEHS, Mol Genet Lab, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM resnick@niehs.nih.gov NR 82 TC 54 Z9 54 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 1998 VL 18 IS 4 BP 1891 EP 1902 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZC751 UT WOS:000072613700013 PM 9528760 ER PT J AU Sharon-Friling, R Richardson, J Sperbeck, S Lee, D Rauchman, M Maas, R Swaroop, A Wistow, G AF Sharon-Friling, R Richardson, J Sperbeck, S Lee, D Rauchman, M Maas, R Swaroop, A Wistow, G TI Lens-specific gene recruitment of zeta-crystallin through Pax6, Nrl-Maf, and brain suppressor sites SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HOMEOBOX-CONTAINING GENE; TRANSCRIPTION FACTOR NRL; PAIRED DOMAIN; DNA-BINDING; GUINEA-PIG; NUCLEAR ONCOPROTEIN; NERVOUS-SYSTEM; EYELESS GENE; EYE LENS; EXPRESSION AB zeta-Crystallin is a taxon-specific crystallin, an enzyme which has undergone direct gene recruitment as a structural component of the guinea pig lens through a Pax6-dependent mechanism, Tissue specificity arises through a combination of effects involving three sites in the lens promoter. The Pax6 site (ZPE) itself shows specificity for an isoform of Pax6 preferentially expressed in lens cells, High-level expression of the promoter requires a second site, identical to an alpha CE2 site or half Maf response element (MARE), adjacent to the Pax6 site. A promoter fragment containing Pax6 and MARE sites gives lens-preferred induction of a heterologous promoter, Complexes binding the MARE in lens nuclear extracts are antigenically related to IVrl, and cotransfection with Nrl elevates zeta-crystallin promoter activity in lens cells, A truncated zeta promoter containing Nrl-MARE and Pax6 sites has a high level of expression in lens cells in transgenic mice but is also active in the brain. Suppression of the promoter in the brain requires sequences between -498 and -385, and a site in this region forms specific complexes in brain extract. A three-level model for lens-specific Pax6-dependent expression and gene recruitment is suggested: (i) binding of a specific isoform of Pax6; (ii) augmentation of expression through binding of Nrl or a related factor; and (iii) suppression of promoter activity in the central nervous system by an upstream negative element in the brain but not in the lens. C1 NEI, Sect Mol Struct & Funct, NIH, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Michigan, WK Kellogg Eye Ctr, Dept Ophthalmol, Ann Arbor, MI 48105 USA. RP Wistow, G (reprint author), NEI, Sect Mol Struct & Funct, NIH, Bldg 6 Room 331, Bethesda, MD 20892 USA. FU NEI NIH HHS [EY01115] NR 68 TC 32 Z9 33 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 1998 VL 18 IS 4 BP 2067 EP 2076 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZC751 UT WOS:000072613700032 PM 9528779 ER PT J AU Cantwell, CA Sterneck, E Johnson, PF AF Cantwell, CA Sterneck, E Johnson, PF TI Interleukin-6-specific activation of the C/EBP delta gene in hepatocytes is mediated by Stat3 and Sp1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACUTE-PHASE RESPONSE; EPIDERMAL GROWTH-FACTOR; DNA-BINDING PROTEIN; TRANSCRIPTION FACTOR; SIGNAL-TRANSDUCTION; NUCLEAR PROTEINS; JUNB PROMOTER; FAMILY; EXPRESSION; ISOFORMS AB C/EBP delta (CCAAT/enhancer binding protein delta) has been implicated as a regulator of acute-phase response (APR) genes in hepatocytes. Its expression increases dramatically in liver during the APR and can be induced in hepatic sell lines by interleukin-6 (IL-6), an acute-phase mediator that activates transcription of many APR genes, Here we have investigated the mechanism by which C/EBP delta expression is regulated by IL-6 in hepatoma cells, C/EBP delta promoter sequences to -125 bp are sufficient for IL-6 inducibility of a reporter gene and include apt APR element (APRE) that is essential for PL-Ci responsiveness, DNA binding experiments and transactivation assays demonstrate that Stat3, but mot Stat1, interacts with this APRE. Two Spl sites, one of which is adjacent to the APRE, are required for Ik-e induction and transactivation by Stat3. Thus, Stall and Spl function cooperatively to activate the C/EBP delta promoter. Replacement of the APRE with Stat binding elements (SBEs) from the ICAM-1 or C/EBP beta promoter, both of which recognize both Stat1 and Stat3, confers responsiveness to gamma interferon, a cytokine that selectively activates Stat1. Sequence comparisons suggest that the distinct Stat binding specificities of the C/EBP delta and C/EBP beta SBEs are determined primarily by a single base pair difference. Our findings indicate that the cytokine specificity of C/EBP delta gene expression is governed by the APRE sequence. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Eukaryot Transcript Regulat Grp, Frederick, MD 21702 USA. RP Johnson, PF (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Eukaryot Transcript Regulat Grp, POB B, Frederick, MD 21702 USA. EM johnsopf@ncifcrf.gov RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 NR 55 TC 137 Z9 140 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 1998 VL 18 IS 4 BP 2108 EP 2117 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZC751 UT WOS:000072613700036 PM 9528783 ER PT J AU Myers, CA Schmidhauser, C Mellentin-Michelotti, J Fragoso, G Roskelley, CD Casperson, G Mossi, R Pujuguet, P Hager, G Bissell, MJ AF Myers, CA Schmidhauser, C Mellentin-Michelotti, J Fragoso, G Roskelley, CD Casperson, G Mossi, R Pujuguet, P Hager, G Bissell, MJ TI Characterization of BCE-1, a transcriptional enhancer regulated by prolactin and extracellular matrix and modulated by the state of histone acetylation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BETA-CASEIN GENE; MAMMARY EPITHELIAL-CELLS; DNA-BINDING PROTEINS; FUNCTIONAL-DIFFERENTIATION; MAMMALIAN-CELLS; SIGNAL-TRANSDUCTION; CHROMATIN STRUCTURE; RESPONSE ELEMENT; SODIUM-BUTYRATE; GROWTH-FACTOR AB We have previously described a 160-bp enhancer (BCE-1) in the bovine beta-casein gene that is activated in the presence of prolactin and extracellular matrix (ECM). Here we report the characterization of the enhancer by deletion and site-directed mutagenesis, electrophoretic mobility shift analysis, and in vivo footprinting. Two essential regions were identified by analysis of mutant constructions: one binds C/EBP-beta and the other binds MGF/STAT5 and an as-yet-unidentified binding protein. However, no qualitative or quantitative differences in the binding of these proteins were observed in electrophoretic mobility shift analysis using nuclear extracts derived from cells cultured in the presence or absence of ECM with or without pro!actin, indicating that prolactin-and ECM-induced transcription was not dependent an the availability of these factors in the functional cell lines employed, An in vivo footprinting analysis of the factors bound to nuclear chromatin in the presence or absence of ECM and/or prolactin found no differences in the binding of C/EBP-beta but did not protide definitive results for the other factors, Neither ECM nor prolactin activated BCE-1. in transient transactions, suggesting that the chromosomal structure of the integrated template may he required for ECM-induced transcription, Further evidence is that treatment of cells with inhibitors of histone deacetylase was sufficient to induce transcription of integrated BCE-I in the absence of ECM. Together, these results suggest that the ECM induces a complex interaction between the enhancer-bound transcription factors, the basal transcriptional machinery, and a chromosomally integrated template responsive to the acetylation state of the histones. C1 Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA. NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. Monsanto Co, Searle Res Div, Chesterfield, MO 63017 USA. Univ Zurich Irchel, Inst Veterinarian Biochem, CH-8057 Zurich, Switzerland. RP Bissell, MJ (reprint author), Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, 1 Cyclotron Rd,Bldg 83-101, Berkeley, CA 94720 USA. EM mjbissell@lbl.gov RI Roskelley, Calvin /F-4630-2011 NR 66 TC 84 Z9 86 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 1998 VL 18 IS 4 BP 2184 EP 2195 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZC751 UT WOS:000072613700043 PM 9528790 ER PT J AU Romano, PR Garcia-Barrio, MT Zhang, XL Wang, QZ Taylor, DR Zhang, F Herring, C Mathews, MB Qin, J Hinnebusch, AG AF Romano, PR Garcia-Barrio, MT Zhang, XL Wang, QZ Taylor, DR Zhang, F Herring, C Mathews, MB Qin, J Hinnebusch, AG TI Autophosphorylation in the activation loop is required for full kinase activity in vivo of human and yeast eukaryotic initiation factor 2 alpha kinases PKR and GCN2 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DOUBLE-STRANDED-RNA; DEPENDENT PROTEIN-KINASE; CATALYTIC SUBUNIT; INTERFERON ACTION; SACCHAROMYCES-CEREVISIAE; TRANSLATIONAL CONTROL; CRYSTAL-STRUCTURE; IN-VITRO; BINDING; MECHANISM AB The human double-stranded RNA-dependent protein kinase (PKR) is an important component of the interferon response to virus infection, The activation of PKR is accompanied by autophosphorylation at multiple sites, including one in the N-terminal regulatory region (Thr-258) that is required for full kinase activity, Several protein kinases are activated by phosphorylation in the region between kinase subdomains VII and VIII, referred to as the activation loop, We show that Thr-446 and Thr-451 in the PKR activation loop are required in vivo and in vitro for high-level kinase activity, Mutation of either residue to Ala impaired translational control by PKR in yeast cells and COS1 cells and led to tumor formation in mice, These mutations also impaired autophosphorylation and eukaryotic initiation factor 2 subunit alpha (eIF2 alpha) phosphorylation by PKR in vitro. Whereas the Ala-446 substitution substantially reduced PKR function, the mutant kinase containing Ala-451 was completely inactive, PKR specifically phosphorylated Thr-446 and Thr-451 in synthetic peptides in vitro, and mass spectrometry analysis of PKR phosphopeptides confirmed that Thr-446 is an autophosphorylation site in vivo. Substitution of Glu-490 in subdomain Ii of PKR partially restored kinase activity when combined with the Ala-451 mutation. This finding suggests that the interaction between subdomain X and the activation loop, described previously for MAP kinase, is a regulatory feature conserved in PKR. We found that the yeast eIF2 alpha kinase GCN2 autophosphorylates at Thr-882 and Thr-887, located in the activation loop at exactly the same positions as Thr-446 and Thr-451 in PKR, Thr-887 was more critically required than was Thr-882 for GCN2 kinase activity, paralleling the relative importance of Thr-446 and Thr-451 in PKR. These results indicate striking similarities between GCN2 and PKR in the importance of autophosphorylation and the conserved Thr residues in the activation loop. C1 NICHHD, Eukaryot Mol Genet Lab, Bethesda, MD 20892 USA. NHLBI, Biophys Chem Lab, Bethesda, MD 20892 USA. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. RP NICHHD, Eukaryot Mol Genet Lab, Bldg 6A,Room B1A-13A, Bethesda, MD 20892 USA. EM ahinnebusch@nih.gov FU NIAID NIH HHS [AI 34552, R01 AI034552] NR 55 TC 180 Z9 182 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 1998 VL 18 IS 4 BP 2282 EP 2297 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZC751 UT WOS:000072613700052 PM 9528799 ER PT J AU Zorad, S Alsasua, A Saavedra, JM AF Zorad, S Alsasua, A Saavedra, JM TI Decreased expression of natriuretic peptide A receptors and decreased cGMP production in the choroid plexus of spontaneously hypertensive rats SO MOLECULAR AND CHEMICAL NEUROPATHOLOGY LA English DT Article DE hypertension; natriuretic peptides; receptor subtypes; choroid plexus; cGMP; cAMP ID SIGNAL-TRANSDUCTION SYSTEM; ADENYLATE-CYCLASE; BINDING-SITES; CYCLIC-GMP; PAROTID-GLAND; BRAIN; LOCALIZATION; FORSKOLIN; AUTORADIOGRAPHY; INVOLVEMENT AB Atrial natriuretic peptide receptor (ANP) subtypes and their signal transduction response were characterized in choroid plexus of spontaneously hypertensive (SHR) and normotensive (WKY) rats. We found two ANP receptor subtypes, guanylate cyclase coupled and uncoupled, in both rat strains. Binding of ANP was lower in SHR choroid plexus when compared to WKY. The lower ANP binding in SHR was the result of a decrease of binding to the guanylate cyclase-coupled receptor subtype A, a decrease that correlated well with the decreased ANP-induced cGMP formation in SHR. Forskolin stimulated cGMP production to the same extent in both strains. In WKY rats, ANP increased basal and forskolin-stimulated cAMP production; conversely, in SHR, ANP did not affect the basal level of cAMP and inhibited the forskolin-stimulated cAMP production. These results demonstrate differences in ANP receptor subtype expression, and ANP signal transduction in choroid plexus of hypertensive and normotensive rats, which is of possible significance to the central mechanisms of blood pressure control. C1 NIMH, Pharmacol Sect, Bethesda, MD 20892 USA. RP Saavedra, JM (reprint author), NIMH, Pharmacol Sect, 10 Ctr Dr,Bldg 10-2D57, Bethesda, MD 20892 USA. EM Saavedrj@irp.nimh.nih.gov NR 45 TC 6 Z9 6 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1044-7393 J9 MOL CHEM NEUROPATHOL JI Mol. Chem. Neuropathol. PD APR PY 1998 VL 33 IS 3 BP 209 EP 222 DI 10.1007/BF02815183 PG 14 WC Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA ZU481 UT WOS:000074202400006 PM 9642674 ER PT J AU Dooijes, D van Beest, M van de Wetering, M Boulanger, G Jones, T Clevers, H Mortin, MA AF Dooijes, D van Beest, M van de Wetering, M Boulanger, G Jones, T Clevers, H Mortin, MA TI Genomic organization of the segment polarity gene pan in Drosophila melanogaster SO MOLECULAR AND GENERAL GENETICS LA English DT Article DE Drosophila melanogaster; high mobility group proteins (HMG); lymphoid enhancer binding protein (LEF); T cell factor (TCF); Wnt/wingless signaling ID HMG-BOX; TRANSCRIPTION FACTOR; ALPHA-ENHANCER; BETA-CATENIN; PROTEIN; TCF-1; LEF-1; CLONING; EMBRYOS; FAMILY AB We previously described the molecular cloning of a mammalian T cell factor 1 (TCF-1)-like protein from Drosophila melanogaster, encoded by the pangolin (pan) locus, and demonstrated that it consists of a DNA binding domain similar to that of other high mobility group proteins and a protein-protein interaction domain that binds beta-catenin (Armadillo in Drosophila) but that it lacks a transcriptional activation domain. Here we show that the pan locus spans approximately 50 kb and the mRNA results from the splicing of 13 exons. We note remarkable conservation of the exon/intron boundaries between the human and D. melanogaster genes, suggesting that they share a common ancestor. Chromosomal in situ hybridization locates pan to the base of chromosome 4, near the cubitus interruptus locus. Restriction map and sequence analyses confirm their close proximity. The small fourth chromosome undergoes little or no recombination and was previously reported to lack DNA polymorphisms; however, we note two DNA polymorphisms occurring in three combinations within the pan locus, demonstrating the presence of synonymous substitutions and the past occurrence of recombination. We present evidence suggesting that the protein encoded by pan is more similar to mammalian TCF-1 and Caenorhabditis elegans POP-1 than to mammalian LEF-1. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Univ Utrecht Hosp, Dept Immunol, NL-3508 GA Utrecht, Netherlands. RP Mortin, MA (reprint author), NCI, Biochem Lab, NIH, 37 Convent Dr,Bldg 37,Rm 4D-25, Bethesda, MD 20892 USA. EM MORTINM@DC37A.NCI.NIH.GOV RI Mortin, Mark/B-4251-2008 NR 32 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0026-8925 J9 MOL GEN GENET JI Mol. Gen. Genet. PD APR PY 1998 VL 258 IS 1-2 BP 45 EP 52 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA ZP144 UT WOS:000073721200006 PM 9613571 ER PT J AU Zhang, LX Smith, MA Li, XL Weiss, SRB Post, RM AF Zhang, LX Smith, MA Li, XL Weiss, SRB Post, RM TI Apoptosis of hippocampal neurons after amygdala kindled seizures SO MOLECULAR BRAIN RESEARCH LA English DT Article DE apoptosis; programmed cell death; Bax; Bcl-2; kindling; epilepsy; hippocampus ID TEMPORAL-LOBE EPILEPSY; PROGRAMMED CELL-DEATH; UP-REGULATION; DNA FRAGMENTATION; MESSENGER-RNA; SYNAPTIC REORGANIZATION; SYMPATHETIC NEURONS; RAT HIPPOCAMPUS; SELECTIVE LOSS; KAINIC ACID AB Seizure-induced neuronal damage may involve both excitotoxic and apoptotic (programmed cell death) mechanisms. In the present study, we used an amygdala kindled seizure model to study whether apoptotic cell death occurs. To evaluate apoptosis, we counted the numbers of cells that had DNA fragments labeled at the 3' end with digoxigenin using terminal transferase (ApopTag, Oncor). Additionally, the expression of Bax and Bcl-2, two genes associated with apoptotic cell death, was also measured following kindled seizures. We found that the number of ApopTag-positive cells in the hippocampus increased 30.4% after one kindled seizure and 82.5% after 20 seizures compared to sham controls. The ApopTag-labeled cells could be mainly interneurons of the hippocampal formation, although additional studies are required. Preferential vulnerability of inhibitory interneurons is consistent with previous studies on seizure-induced cell, loss. These results, coupled with our findings that the ratio of Bax/Bcl-2 expression is increased in the hippocampus by seizures, suggest that apoptosis of hippocampal interneurons may lead to dysinhibition in the hippocampus and increased seizure susceptibility. (C) 1998 Elsevier Science B.V. C1 Uniformed Serv Univ Hlth Sci, Dept Psychiat, Dept Def, Bethesda, MD 20814 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20982 USA. RP Zhang, LX (reprint author), Uniformed Serv Univ Hlth Sci, Dept Psychiat, Dept Def, Bethesda, MD 20814 USA. NR 53 TC 53 Z9 54 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD APR PY 1998 VL 55 IS 2 BP 198 EP 208 DI 10.1016/S0169-328X(97)00316-1 PG 11 WC Neurosciences SC Neurosciences & Neurology GA ZU484 UT WOS:000074202700002 ER PT J AU Cannon, RE Spalding, JW Virgil, KM Faircloth, RS Humble, MC Lacks, GD Tennant, RW AF Cannon, RE Spalding, JW Virgil, KM Faircloth, RS Humble, MC Lacks, GD Tennant, RW TI Induction of transgene expression in Tg.AC (v-Ha-ras) transgenic mice concomitant with DNA hypomethylation SO MOLECULAR CARCINOGENESIS LA English DT Article DE v-Ha-ras; methylation; tumorgenesis; gene expression; wound repair; skin cancer; stem cell ID HUMAN CANCERS; MOUSE SKIN; METHYLATION; PAPILLOMAS; ONCOGENES; GENE AB Tg.AC transgenic mice have a transgene composed of a zeta-globin transcriptional control region, a v-Ha-ras coding region, and a simian virus 40 3' polyadenylation signal sequence. Induced ectopic expression of the transgene by chemical treatment or full-skin-thickness wounding leads to the development of skin papillomas. Reverse transcription-polymerase chain reaction assays and protein blotting indicated that the transgene was expressed 16-28 d after full-skin-thickness surgical wounding. Normal unwounded skin did not express the transgene. DNA blotting indicated that the position of the transgene remained stable during wound-induced tumorigenesis. Concomitant with the v-Ha-ras mRNA and protein expression was the hypomethylation of specific MspI/HpaII sites with in the transgene. These results a re consistent with the hypothesis that hypomethylation is required for the induced and sustained expression of the Tg.AC v-Ha-ras transgene in spontaneous and induced tumors in Tg.AC mice. (C) 1998 Wiley-Liss, Inc. C1 NIEHS, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. RP Cannon, RE (reprint author), NIEHS, Lab Environm Carcinogenesis & Mutagenesis, POB 12233, Res Triangle Pk, NC 27709 USA. NR 16 TC 24 Z9 24 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD APR PY 1998 VL 21 IS 4 BP 244 EP 250 DI 10.1002/(SICI)1098-2744(199804)21:4<244::AID-MC3>3.0.CO;2-K PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA ZL582 UT WOS:000073448800003 PM 9585254 ER PT J AU Gruter, P Tabernero, C von Kobbe, C Schmitt, C Saavedra, C Bachi, A Wilm, M Felber, BK Izaurralde, E AF Gruter, P Tabernero, C von Kobbe, C Schmitt, C Saavedra, C Bachi, A Wilm, M Felber, BK Izaurralde, E TI TAP, the human homolog of Mex67p, mediates CTE-dependent RNA export from the nucleus SO MOLECULAR CELL LA English DT Article ID SIMIAN RETROVIRUS TYPE-1; CAP-BINDING-PROTEIN; MESSENGER-RNA; ELEMENT; IDENTIFICATION; PEPTIDES; SEQUENCE; SIGNAL; SNRNAS AB The constitutive transport element (CTE) of the type D retroviruses promotes nuclear export of unspliced viral RNAs apparently by recruiting host factor(s) required for export of cellular messenger RNAs. Here, we report the identification of TAP as the cellular factor that specifically binds to wild-type CTE but not to export-deficient CTE mutants. Microinjection experiments performed in Xenopus oocytes demonstrate that TAP directly stimulates CTE-dependent export. Furthermore, TAP overcomes the mRNA export block caused by the presence of saturating amounts of CTE RNA. Thus, TAP, like its yeast homolog Mex67p, is a bona fide mRNA nuclear export mediator. TAP is the second cellular RNA binding protein shown to be directly involved in the export of its target RNA. C1 Univ Geneva, Dept Biol Mol, CH-1211 Geneva 4, Switzerland. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Human Retrovirus Pathogenesis Grp, Frederick, MD 21702 USA. European Mol Biol Lab, D-69117 Heidelberg, Germany. RP Izaurralde, E (reprint author), Univ Geneva, Dept Biol Mol, 30 Quai Ernest Ansermet, CH-1211 Geneva 4, Switzerland. RI Izaurralde, Elisa/G-3239-2012; OI Izaurralde, Elisa/0000-0001-7365-2649 NR 41 TC 402 Z9 410 U1 2 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD APR PY 1998 VL 1 IS 5 BP 649 EP 659 DI 10.1016/S1097-2765(00)80065-9 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZK610 UT WOS:000073342400003 PM 9660949 ER PT J AU Tomonaga, T Michelotti, GA Libutti, D Uy, A Sauer, B Levens, D AF Tomonaga, T Michelotti, GA Libutti, D Uy, A Sauer, B Levens, D TI Unrestraining genetic processes with a protein-DNA hinge SO MOLECULAR CELL LA English DT Article ID SITE-SPECIFIC RECOMBINATION; NUCLEAR RIBONUCLEOPROTEIN-K; INTEGRATION HOST FACTOR; CRE RECOMBINASE; C-MYC; BINDING; TRANSCRIPTION; BACTERIOPHAGE-P1; CHROMATIN; PROMOTER AB Genetic processes require direct interactions between proteins bound at nonadjacent cis elements. Because duplex DNA is rigid, either the protein-protein interactions are strong enough to deform the double helix or some feature of the intervening DNA must encourage juxtaposition of separated sites. For example, bent DNA can bring together only certain precisely positioned cis elements with the same helical phase. Interposing a DNA segment that both bends and twists easily to create a universal joint would provide an even more general mechanism to promote the association of separated sites regardless of position. A cis element of the human c-myc gene, known to be melted in vivo, and its associated single-strand DNA binding protein were examined and found to comprise just such a protein-DNA hinge. C1 NCI, Div Clin Sci, Pathol Lab, Bethesda, MD 20892 USA. NIDDKD, Biochem & Metab Lab, Bethesda, MD 20892 USA. RP Levens, D (reprint author), NCI, Div Clin Sci, Pathol Lab, Bethesda, MD 20892 USA. RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X NR 28 TC 34 Z9 34 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD APR PY 1998 VL 1 IS 5 BP 759 EP 764 DI 10.1016/S1097-2765(00)80075-1 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZK610 UT WOS:000073342400013 PM 9660959 ER PT J AU Lee, J Novoradovskaya, N Rundquist, B Redwine, J Saltini, C Brantly, M AF Lee, J Novoradovskaya, N Rundquist, B Redwine, J Saltini, C Brantly, M TI alpha(1)-antitrypsin nonsense mutation associated with a retained truncated protein and reduced mRNA SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE alpha(1)-antitrypsin; nonsense mutation; mRNA; truncated protein ID MESSENGER-RNA DEGRADATION; ALPHA-1-ANTITRYPSIN NULLGRANITE-FALLS; BETA-GLOBIN GENE; ENDOPLASMIC-RETICULUM; FRAMESHIFT MUTATION; CODON MUTATIONS; NULL ALLELE; CODING EXON; DEFICIENCY; MECHANISM AB alpha(1)-Antitrypsin (alpha 1AT) provides the major protection in the lung against neutrophil elastase-mediated proteolysis. Inheritance of alpha 1AT deficiency alleles is associated with an increased risk of emphysema and liver disease. (alpha 1AT null alleles cause the total absence of serum alpha 1AT and represent the ultimate in a continuum of alleles associated with alpha 1AT deficiency. The molecular mechanisms responsible for absence of serum alpha 1AT include splicing abnormalities, deletion of alpha 1AT coding exons, and premature stop codons. We identified an Italian individual with asthma, emphysema, and a very low level of serum alpha 1AT. DNA sequencing demonstrated the Mprocida deficiency allele and a novel null allele, QOtrastevere (c654 G --> A, W194Z), a nonsense mutation near the intron 2 (IVS2) splice acceptor site. To determine the molecular basis of QOtrastevere and specifically to evaluate whether this nonsense mutation interfered with mRNA processing by altered splicing, we used a Chinese hamster ovary cell line permanently transfected with QOtrastevere or normal M alpha 1AT with and without IVS2. Northern blot analysis demonstrated that the normal M construct, with or without IVS2, expressed alpha 1AT mRNA of a similar size. The nonsense mutation was associated with moderately reduced alpha 1AT mRNA regardless of the presence or absence of IVS2. Reduction in alpha 1AT mRNA regardless of the opportunity for splicing supports a translational-translocation model as the cause of reduced (alpha 1AT mRNA rather than the nuclear scanning model. Pulse-chase studies followed by immunoprecipitation demonstrated an endoplasmic reticulum-retained 31 kDa QOtrastevere (alpha 1AT, which was rapidly degraded. Although mRNA content was moderately reduced, retention and rapid intracellular degradation of the truncated form are the major mechanisms for the absence of secreted alpha 1AT. (C) 1998 Academic Press. C1 NHLBI, Clin Studies Sect, Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. Div Tisiol & Malattie Apparato Resp, Dipartimento Sci Med Oncolog & Radiolog, I-41100 Modena, Italy. RP Lee, J (reprint author), NHLBI, Clin Studies Sect, Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NR 55 TC 9 Z9 9 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD APR PY 1998 VL 63 IS 4 BP 270 EP 280 DI 10.1006/mgme.1998.2680 PG 11 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA ZV078 UT WOS:000074266300004 PM 9635295 ER PT J AU Reissner, K Tayebi, N Stubblefield, BK Koprivica, V Blitzer, M Holleran, W Cowan, T Almashanu, S Maddalena, A Karson, EM Sidransky, E AF Reissner, K Tayebi, N Stubblefield, BK Koprivica, V Blitzer, M Holleran, W Cowan, T Almashanu, S Maddalena, A Karson, EM Sidransky, E TI Type 2 Gaucher disease with hydrops fetalis in an Ashkenazi Jewish family resulting from a novel recombinant allele and a rare splice junction mutation in the glucocerebrosidase locus SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Gaucher disease; glucocerebrosidase activity; recombinant allele; Ashkenazi; hydrops fetalis; neuronopathic; carrier screening ID TARGETED DISRUPTION; FUSION GENE; MOUSE MODEL; PSEUDOGENE; PHENOTYPE AB Gaucher disease, the deficiency of the lysosomal enzyme glucocerebrosidase (EC 3,2.1.45), is frequently encountered in the Ashkenazi Jewish population, Carrier screening for Gaucher disease by enzyme analysis performed during a routine pregnancy indicated that both Ashkenazi parents were carriers, Screening for four common Gaucher mutations was subsequently performed on fetal and parental DNA. None of the common Ashkenazi mutations were identified. However, when exons 9-11 were amplified and digested with NciI to detect the L444P mutation, it appeared that the mother and the fetus had an unusual allele and that the expected paternal allele was not present. When the fetal amniocytes were found to have less than 2% of the normal glucocerebrosidase activity and a fetal sonogram revealed hydrops fetalis, the pregnancy was terminated. The diagnosis of severe type 2 Gaucher disease was confirmed at autopsy. Ultrastructural studies of epidermis from the fetus revealed the characteristic disruption of lamellar bilayers, diagnostic for type 2 Gaucher disease. In subsequent studies of the fetal DNA, long-template polymerase chain reaction amplification revealed one appropriately sized band (similar to 6,5 kb) and one smaller (similar to 5.2 kb) band. Sequencing of the similar to 5.2-kb fragment identified a novel fusion allele resulting from recombination between the glucocerebrosidase gene and its pseudogene beginning in intron 3, This fusion allele was inherited from the father, The result was confirmed by Southern blot analysis using the enzyme SstII, Sequencing of the 6.5-kb fragment identified a previously described, although rare, T-to-G; splice junction mutation in intron 10 of the maternal allele, which introduced an NciI site, The couple had a subsequent pregnancy which was also found to be affected. This case study identifies a novel recombinant allele and an unusual splice junction mutation, and demonstrates that even in the Ashkenazi population, screening for common mutations may not accurately identify the most severe forms of the disease. (C) 1998 Academic Press. C1 NIMH, Clin Neurosci Branch, IRP, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Div Human Genet, Baltimore, MD 21201 USA. Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94121 USA. Columbia Hosp Women, Washington, DC 20037 USA. Genet & IVF Inst, Fairfax, VA 22031 USA. RP Reissner, K (reprint author), NIMH, Clin Neurosci Branch, IRP, NIH, Bethesda, MD 20892 USA. NR 20 TC 23 Z9 23 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD APR PY 1998 VL 63 IS 4 BP 281 EP 288 DI 10.1006/mgme.1998.2675 PG 8 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA ZV078 UT WOS:000074266300005 PM 9635296 ER PT J AU Basta, M Van Goor, F Stojilkovic, SS Metcalfe, DD Billings, E AF Basta, M Van Goor, F Stojilkovic, SS Metcalfe, DD Billings, E TI Inhibition of C3a/C5a-induced calcium mobilization in human mast cells by high-dose intravenous immunoglobulins (IVIG) SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 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 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD APR-MAY PY 1998 VL 35 IS 6-7 SI SI MA 19 BP 335 EP 335 DI 10.1016/S0161-5890(98)90551-X PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 121RF UT WOS:000076027200020 ER PT J AU Chavany, C Jendoubi, M AF Chavany, C Jendoubi, M TI Biology and potential strategies for the treatment of G(M2) gangliosides SO MOLECULAR MEDICINE TODAY LA English DT Review ID MUCOPOLYSACCHARIDOSIS TYPE-VII; BONE-MARROW TRANSPLANTATION; HUMAN NEURAL PROGENITORS; CENTRAL-NERVOUS-SYSTEM; TAY-SACHS-DISEASE; LYSOSOMAL STORAGE; GENE-TRANSFER; SANDHOFF DISEASES; MOUSE MODELS; MICE AB The G(M2) gangliosidoses are a group of heritable neurodegenerative disorders caused by excessive accumulation of the ganglioside G(M2) owing to deficiency in beta-hexosaminidase activity. Tay-Sachs and Sandhoff diseases have similar clinical phenotypes resulting from a deficiency in human exhosaminidase alpha and beta subunits, respectively. The lack of treatment for G(M2) gangliosidoses stimulated interest in developing animal models to understand the molecular mechanisms underlying the various forms of this disease and to test new potential therapies. In this review, we discuss the molecular biology of G(M2) gangliosidoses and the different strategies that have been tested in animal models for the treatment of this genetic disorder, including gene transfer and cell engraftment of neural stem cells engineered to express the hexosaminidase isoenzymes. C1 NIH, Genet & Mol Immunol Sect, Bethesda, MD 20892 USA. RP Chavany, C (reprint author), Milagen Inc, 460 Page Mill Rd, Palo Alto, CA 94306 USA. NR 36 TC 19 Z9 19 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1357-4310 J9 MOL MED TODAY JI Mol. Med. Today PD APR PY 1998 VL 4 IS 4 BP 158 EP 165 DI 10.1016/S1357-4310(98)01227-1 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA ZJ261 UT WOS:000073196300008 PM 9572057 ER PT J AU Engbring, JA Alderete, JF AF Engbring, JA Alderete, JF TI Three genes encode distinct AP33 proteins involved in Trichomonas vaginalis cytoadherence SO MOLECULAR MICROBIOLOGY LA English DT Article ID SUCCINYL-COA SYNTHETASE; ESCHERICHIA-COLI; MOLECULAR CHARACTERIZATION; ALPHA-SUBUNIT; SEQUENCE; MITOCHONDRIAL; PARASITISM; COENZYME; ENZYMES; RNA AB Adherence to host cells is essential for the initiation and maintenance of infection by mucosal pathogens. The protozoan Trichomonas vaginalis colonizes the human urogenital tract via four surface proteins (AP65, AP51, AP33 and AP23). To characterize AP33 further, six cDNA clones were examined. Restriction mapping indicated that the six clones represented th ree sim liar genes. Southern analysis confirmed the existence of three single-copy AP33 genes and suggested a semiconservative genomic arrangement between T. vaginalis isolates. Analysis of full-length sequences determined that each contained a 930bp open reading frame encoding a protein of approximately 33000 Da. Sequence comparisons revealed a high degree of identity at both the DNA and the protein levels. N-terminal protein sequencing established the presence of leader peptides. Each of the three full-length recombinant proteins had a predicted pi of approximately 10, which was verified experimentally for the T. vaginalis AP33 adhesin. A database search revealed that AP33 had significant identity to the succinyl-CoA synthetase alpha-subunit of several different organisms and virtually 100% identity to the reported T. vaginalis subunit. Unlike commercially purchased enzyme, the recombinant proteins retained adhesive properties equal to the natural T. vaginalis AP33. The characteristics of the AP33 protein are similar to those of the other adhesins and emphasize a complex host-parasite relationship. C1 Univ Texas, Hlth Sci Ctr, Dept Microbiol, San Antonio, TX 78284 USA. NIDR, NIH, Bethesda, MD 20892 USA. RP Alderete, JF (reprint author), Univ Texas, Hlth Sci Ctr, Dept Microbiol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIAID NIH HHS [AI07271, AI 18768] NR 40 TC 30 Z9 37 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD APR PY 1998 VL 28 IS 2 BP 305 EP 313 DI 10.1046/j.1365-2958.1998.00784.x PG 9 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA ZJ830 UT WOS:000073258000008 PM 9622355 ER PT J AU Honkakoski, P Moore, R Washburn, KA Negishi, M AF Honkakoski, P Moore, R Washburn, KA Negishi, M TI Activation by diverse xenochemicals of the 51-base pair phenobarbital-responsive enhancer module in the CYP2B10 gene SO MOLECULAR PHARMACOLOGY LA English DT Article ID INDUCTION; RAT; CYTOCHROME-P-450; TRANSCRIPTION; CHEMICALS; RECEPTOR AB By extending previous studies of the phenobarbital (PB)-responsive 132-base pair (bp) enhancer sequence in the CYP2B10 gene, we have delimited a 51-bp enhancer element that is fully inducible by PB in mouse primary hepatocytes. Sixteen structurally unrelated phenobarbital-type inducers activated the 51-bp enhancer element in transient transfection assays. The results thus indicate that most PB-type inducers, if not all inducers, increase the transcription of the CYP2B10 gene by activating this 51-bp element, now designated PB-responsive enhancer module or PBREM. C1 NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov OI Honkakoski, Paavo/0000-0002-4332-3577 NR 26 TC 139 Z9 145 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD APR PY 1998 VL 53 IS 4 BP 597 EP 601 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZJ459 UT WOS:000073217800001 PM 9547348 ER PT J AU Bengel, D Murphy, DL Andrews, AM Wichems, CH Feltner, D Heils, A Mossner, R Westphal, H Lesch, KP AF Bengel, D Murphy, DL Andrews, AM Wichems, CH Feltner, D Heils, A Mossner, R Westphal, H Lesch, KP TI Altered brain serotonin homeostasis and locomotor insensitivity to 3,4-methylenedioxymethamphetamine ("ecstasy") in serotonin transporter-deficient mice SO MOLECULAR PHARMACOLOGY LA English DT Article ID CARRIER-MEDIATED RELEASE; RAT-BRAIN; MDMA; DOPAMINE; NEURONS; GENE; METHYLENEDIOXYMETHAMPHETAMINE; NOREPINEPHRINE; MORPHOGENESIS; PHARMACOLOGY AB The sodium-dependent, high affinity serotonin [5-hydroxytryptamine (5-HT)] transporter (5-HTT) provides the primary mechanism for inactivation of 5-HT after its release into the synaptic cleft. To further evaluate the function of the 5-HTT, the murine gene was disrupted by homologous recombination. Despite evidence that excess extracellular 5-HT during embryonic development, including that produced by drugs that inhibit the 5-HTT, may lead to severe craniofacial and cardiac malformations, no obvious developmental phenotype was observed in the 5-HTT-/- mice. High affinity [H-3]5-HT uptake was completely absent in 5-HTT-/- mice, confirming a physiologically effective knockout of the 5-HTT gene. 5-HTT binding sites labeled with [I-125]3 beta-(4'-iodophenyl)tropan-2 beta-carboxylic acid methyl ester were reduced in a gene dose-dependent manner, with no demonstrable binding in 5-HTT-/- mutants. In adult 5-HTT-/- mice, marked reductions (60-80%) in 5-HT concentrations were measured in several brain regions. While (+)-amphetamine-induced hyperactivity did not differ across genotypes, the locomotor enhancing effects of (+)-3,4-methylenedioxymethamphetamine, a substituted amphetamine that releases 5-HT via a transporter-dependent mechanism, was completely absent in 5-HTT-/- mutants. Together, these data suggest that the presence of a functional 5-HTT is essential for brain 5-HT homeostasis and for 3,4-methylenedioxymethamphetamine-induced hyperactivity. C1 Univ Wurzburg, Dept Psychiat, D-97080 Wurzburg, Germany. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. NICHHD, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA. RP Lesch, KP (reprint author), Univ Wurzburg, Dept Psychiat, Fuchsleinstr 15, D-97080 Wurzburg, Germany. EM kplesch@mail.uni-wuerzburg.de RI Andrews, Anne/B-4442-2011; Lesch, Klaus-Peter/J-4906-2013 OI Andrews, Anne/0000-0002-1961-4833; Lesch, Klaus-Peter/0000-0001-8348-153X NR 46 TC 464 Z9 472 U1 4 U2 21 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD APR PY 1998 VL 53 IS 4 BP 649 EP 655 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZJ459 UT WOS:000073217800007 PM 9547354 ER PT J AU Ishitani, R Tanaka, M Sunaga, K Katsube, N Chuang, DM AF Ishitani, R Tanaka, M Sunaga, K Katsube, N Chuang, DM TI Nuclear localization of overexpressed glyceraldehyde-3-phosphate dehydrogenase in cultured cerebellar neurons undergoing apoptosis SO MOLECULAR PHARMACOLOGY LA English DT Article ID URACIL DNA-GLYCOSYLASE; AGE-INDUCED APOPTOSIS; SKELETAL-MUSCLE; NITRIC-OXIDE; PROTEIN; CELL; EXPRESSION; BINDING; DEATH; GENE AB We recently reported that overexpression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC 1.2.1.12) is directly involved in cytosine arabinonucleoside (ara-C)- and low K+-induced neuronal death of cultured cerebellar granule cells. The former is entirely due to apoptosis, whereas the latter involves both apoptosis and necrosis. We examined the subcellular distribution of the overexpressed GAPDH occurring during apoptosis by using both subcellular fractionation and immunocytochemistry with a monoclonal antibody directed against this overexpressed protein. When immature cerebellar neurons were exposed to ara-C, an overexpression of GAPDH was observed, primarily in the nuclear fraction. In contrast, low K+ exposure of mature cerebellar neurons induced the overexpression of GAPDH not only in the nuclear fraction but also in the mitochondrial fraction. In both paradigms, no significant change of GAPDH levels occurred in the microsomal and cytosolic fractions. Moreover, pretreatment with GAPDH antisense oligonucleotide or classic apoptotic inhibitors clearly suppressed the accumulation of GAPDH protein in these subcellular loci. This discrete nuclear localization of GAPDH during apoptosis was supported further by immunoelectron microscopy. Quantitative assessment of GAPDH immunogold labeling revealed that a similar to 5-fold increase in the intensity of gold particles was observed within the nucleus of apoptotic cells. Thus, the current results raise the possibility that neuronal apoptosis may be triggered by GAPDH accumulation in the nucleus, resulting in perturbation of nuclear function and ultimate cell death. C1 Josai Univ, Grp Cellular Neurobiol, Sakado, Saitama 35002, Japan. Ono Pharmaceut Co Ltd, Chuo Ku, Osaka 541, Japan. NIMH, Mol Neurobiol Sect, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Ishitani, R (reprint author), Josai Univ, Grp Cellular Neurobiol, Sakado, Saitama 35002, Japan. NR 38 TC 88 Z9 93 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD APR PY 1998 VL 53 IS 4 BP 701 EP 707 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZJ459 UT WOS:000073217800014 PM 9547361 ER PT J AU Mori, C Nakamura, N Welch, JE Gotoh, H Goulding, EH Fujioka, M Eddy, EM AF Mori, C Nakamura, N Welch, JE Gotoh, H Goulding, EH Fujioka, M Eddy, EM TI Mouse spermatogenic cell-specific type 1 hexokinase (mHk1-s) transcripts are expressed by alternative splicing from the mHk1 gene and the HK1-S protein is localized mainly in the sperm tail SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Article DE hexokinase 1; mouse; testis; sperm; alternative splicing; gene expression ID AMINO-ACID-SEQUENCE; PORIN-BINDING DOMAIN; GLUCOKINASE GENE; CLONED CDNA; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; MONOCLONAL-ANTIBODIES; MAMMALIAN HEXOKINASE; RAT HEXOKINASE; MESSENGER-RNA; CLONING AB Unique type 1 hexokinase (HK1) mRNAs are present in mouse spermatogenic cells (mHk1-s). They encode a spermatogenic cell-specific sequence region (SSR) but not the porin-binding domain (PBD) necessary for HK1 binding to porin on the outer mitochondrial membrane. This study determined the origin of the multiple Hk1-s transcripts in mouse spermatogenic cells and verified that they are translated in mouse spermatogenic cells. It also showed that a single mHk1 gene encodes the mHk1 transcripts of somatic cells and the mHk1-sa and mHk1-sb transcripts of spermatogenic cells, that alternative exons are used during mHk1 gene expression in mouse spermatogenic cells, and that mHK1-S is translated in mouse spermatogenic cells and is localized mainly with the fibrous sheath in the tail region, not with the mitochondria in the midpiece of mouse sperm. (C) 1998 Wiley-Liss, Inc. C1 Kyoto Univ, Fac Med, Dept Anat & Dev Biol, Sakyo Ku, Kyoto 60601, Japan. NIEHS, Gamete Biol Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. US EPA, Reprod Toxicol Branch, Div Dev Toxicol, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. Kyoto Univ, Fac Med, Cent Lab Electron Microscopy, Kyoto, Japan. RP Mori, C (reprint author), Kyoto Univ, Fac Med, Dept Anat & Dev Biol, Sakyo Ku, Kyoto 60601, Japan. NR 47 TC 88 Z9 88 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1040-452X J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD APR PY 1998 VL 49 IS 4 BP 374 EP 385 DI 10.1002/(SICI)1098-2795(199804)49:4<374::AID-MRD4>3.0.CO;2-K PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA YZ351 UT WOS:000072245700004 PM 9508088 ER PT J AU Stoner, GL Agostini, HT Ryschkewitsch, CF Komoly, S AF Stoner, GL Agostini, HT Ryschkewitsch, CF Komoly, S TI JC virus excreted by multiple sclerosis patients and paired controls from Hungary SO MULTIPLE SCLEROSIS LA English DT Article DE demyelination; genotype; polyomavirus; urine ID CEREBROSPINAL-FLUID; BRAIN; TRANSMISSION; GENOME; URINE AB JC virus (JCV), a human polyomavirus, is the agent of the demyelinating disease progressive multifocal leukoencephalopathy (PML). JCV exists in four main genotypes in the USA. Type I, including subtypes Type IA and Type IB, makes up about 64% of strains in the USA and is thought to be of European origin. Type 2 is found in Asia, and Type 3 in Africa. A fourth type is found only in the USA. In general, these genotypes differ in I-2.5% of their DNA sequence. Thirty MS patients and 30 paired controls from Budapest were studied. The clinical course of MS was mainly secondary progressive, and patients were stable at the time of testing. Most of the controls were relatives of the probands: a spouse, parent or child. Overall, 25 of 60 (42%) of the urines tested Positive for ICV by PCR These included 13 of 30 MS patients, and 12 of 30 controls. Genotyping in the VPI gene showed all 25 JCV strains to be Type I. Among the MS Patients, seven were Type IA and six were Type IB. Among the controls, nine were Type IA and three were Type IB. In five pairs of MS patients and controls, both were positive for JCV by PCR Two of these were husband/wife pairs of which one pair was matched for subtype (both Type IA), and the other was not. Two of them were mother/daughter pairs, and both were matched for subtype (both Type IB). These findings demonstrate that ICV Type I predominates among Hungarians, and suggest that parent/child pairs con be used to trace JCV transmission within the MS family. C1 NINDS, Neurotoxicol Sect, NIH, Bethesda, MD 20892 USA. Jahn Ferenc Del Pesti Teaching Hosp, Dept Neurol, Budapest, Hungary. RP Stoner, GL (reprint author), NINDS, Neurotoxicol Sect, NIH, Bldg 36,Room 4A-29, Bethesda, MD 20892 USA. NR 16 TC 14 Z9 14 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD APR PY 1998 VL 4 IS 2 BP 45 EP 48 DI 10.1191/135245898678919564 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA ZJ614 UT WOS:000073234400001 PM 9599332 ER PT J AU Johnson, FM AF Johnson, FM TI The genetic effects of environmental lead SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH LA English DT Review DE lead; heavy metal; mutation; selection; genetics; adaptation; evolution; carcinogenesis; toxicity; mechanism ID DELTA-AMINOLEVULINIC-ACID; METALLOTHIONEIN-LIKE PROTEIN; SISTER-CHROMATID EXCHANGE; METAL-BINDING PEPTIDES; LOW DIETARY CALCIUM; HEAVY-METALS; PORPHOBILINOGEN SYNTHASE; DEHYDRATASE POLYMORPHISM; SALMONELLA-TYPHIMURIUM; AQUATIC ORGANISMS AB This article reviews the effects of lead on genetic systems in the context of lead's various other toxic effects and its abundance and distribution in the environment. Lead is perhaps the longest used and best recognized toxic environmental chemical, yet it continued be used recklessly until only very recently. Lead is thus a lesson in the limitations and strengths of science, human conscience and common sense. Lead has been tested and found to be capable of eliciting a positive response in an extraordinarily wide range of biological and biochemical tests; among them tests for enzyme inhibition, fidelity of DNA synthesis, mutation, chromosome aberrations, cancer and birth defects. It reacts or complexes with many biomolecules and adversely affects the reproductive, nervous, gastrointestinal, immune, renal, cardiovascular, skeletal, muscular and hematopoietic systems as well as developmental processes. It is Likely that lead is a selective agent that continues to act on and influence the genetic structure and future evolution of exposed plant and animal populations. (C) 1998 Elsevier Science B.V. C1 NIEHS, Toxicol Operat Branch, Res Triangle Pk, NC 27709 USA. RP Johnson, FM (reprint author), NIEHS, Toxicol Operat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. NR 206 TC 135 Z9 144 U1 4 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5742 EI 1388-2139 J9 MUTAT RES-REV MUTAT JI Mutat. Res.-Rev. Mutat. Res. PD APR PY 1998 VL 410 IS 2 BP 123 EP 140 DI 10.1016/S1383-5742(97)00032-X PG 18 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA ZQ679 UT WOS:000073892200002 PM 9637233 ER PT J AU Bork, P Koonin, EV AF Bork, P Koonin, EV TI Predicting functions from protein sequences - where are the bottlenecks? SO NATURE GENETICS LA English DT Article ID YEAST CHROMOSOME-III; POSITIONAL CLONING; FRIEDREICHS-ATAXIA; ESCHERICHIA-COLI; SYNDROME GENE; OBESE GENE; WW DOMAIN; DATABASES; DYSTROPHIN; REPEATS AB The exponential growth of sequence data does not necessarily lead to an increase in knowledge about the functions of genes and their products. Prediction of function using comparative sequence analysis is extremely powerful but, if not performed appropriately, may also lead to the creation and propagation of assignment errors. While current homology detection methods can cope with the data flow, the identification, verification and annotation of functional features need to be drastically improved. C1 European Mol Biol Lab, D-69012 Heidelberg, Germany. Max Delbruck Ctr Mol Med, Berlin, Germany. NCBI, NIH, Bethesda, MD USA. RP Bork, P (reprint author), European Mol Biol Lab, Meyerhofstr 1, D-69012 Heidelberg, Germany. EM bork@embl-heidelberg.de RI Bork, Peer/F-1813-2013 OI Bork, Peer/0000-0002-2627-833X NR 74 TC 232 Z9 236 U1 0 U2 11 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 1998 VL 18 IS 4 BP 313 EP 318 DI 10.1038/ng0498-313 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA ZE078 UT WOS:000072755500011 PM 9537411 ER PT J AU Lau, YS Hao, RY Fung, YK Fu, LS Bishop, JF Pfeiffer, RF Mouradian, MM AF Lau, YS Hao, RY Fung, YK Fu, LS Bishop, JF Pfeiffer, RF Mouradian, MM TI Modulation of nigrostriatal dopaminergic transmission by antisense oligodeoxynucleotide against brain-derived neurotrophic factor SO NEUROCHEMICAL RESEARCH LA English DT Article DE brain-derived neurotrophic factor; antisense oligodeoxynucleotide; dopaminergic transmission; substantia nigra pars compacta; striatum; rat ID SUBSTANTIA-NIGRA; RAT BRAIN; CELL-LINE; NEURONS; BDNF; GDNF; PROTECTION; EXTRACTS; INVITRO; SYSTEM AB Brain-derived neurotrophic factor (BDNF) promotes the differentiation and growth of developing dopamine (DA) neurons and supports the survival of mature DA cells in culture. However, the neurotrophic role of endogenous BDNF in the adult DA system in vivo has not been well established. To investigate the hypothesis that blockade of endogenous BDNF expression results in DA dysregulation, we used an Is-mer antisense oligodeoxynucleotide (ODN) targeted to the first ATG codon of the BDNF transcript. The biological activity of the antisense ODN was initially tested in vitro. In cultured dopaminergic MES 23.5 cells, antisense BDNF (20 mu M) effectively reduced BDNF protein expression and cell survival. Furthermore, in primary embryonic mesencephalic cultures, antisense BDNF reduced the number of tyrosine hydroxylase positive neurons and inhibited [H-3]DA uptake in a time- and dose-dependent manner. The specificity of the antisense molecule was confirmed by comparing its effects with those of a control ODN having the same base composition but in scrambled sequence. In rats, two days following an intranigral or intrastriatal injection of antisense BDNF (0.5 mu g), we observed a two-fold and five-fold increase in nigral DA levels, respectively, but no change in striatal DA content. Seven days after an intrastriatal antisense BDNF injection, DA levels were elevated in the striatum apparently due to decreased DA turnover. These observations suggest that inhibition of endogenous BDNF expression tends to augment rather than inhibit nigrostriatal DA transmission. Thus, the biological effects of endogenous BDNF on the nigrostriatal DA system in the adult organism merits further investigation. C1 Univ Missouri, Sch Pharm, Div Pharmacol, Kansas City, MO 64108 USA. Univ Tennessee, Dept Neurol, Memphis, TN 38163 USA. Univ Nebraska, Med Ctr, Coll Dent, Dept Oral Biol, Lincoln, NE 68583 USA. NINDS, Expt Therapeut Branch, Bethesda, MD 20892 USA. RP Lau, YS (reprint author), Univ Missouri, Sch Pharm, Div Pharmacol, 2411 Holmes St, Kansas City, MO 64108 USA. OI Mouradian, M. Maral/0000-0002-9937-412X NR 26 TC 14 Z9 14 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD APR PY 1998 VL 23 IS 4 BP 525 EP 532 DI 10.1023/A:1022482518292 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA ZG668 UT WOS:000073027200010 PM 9566587 ER PT J AU Williams, WM Hayakawa, T Grange, E Rapoport, SI AF Williams, WM Hayakawa, T Grange, E Rapoport, SI TI Arecoline stimulation of radiolabeled arachidonate incorporation from plasma into brain microvessels of awake rat SO NEUROCHEMICAL RESEARCH LA English DT Article DE arachidonate; cerebral microvessels; fatty acids; in vivo incorporation; palmitate ID ENDOTHELIAL-CELLS AB The cholinergic agonist, arecoline, was used to examine the effects of cholinergic stimulation upon incorporation of radiolabeled arachidonic acid from blood into cerebral microvessels of awake rats. Animals received a single I.P. injection of arecoline (1 mg/kg) followed 3 to 5 minutes later by a 5 minute intravenous infusion of [1-C-14]arachidonic acid (API) (170 mu Ci/kg) via the femoral vein; Timed arterial blood samples were collected over 20 minutes following the start of infusion, after which the animal was killed, and the brain was removed. The incorporation coefficient k* for [1-C-14]AA was approximately 2-fold higher in microvessels isolated from arecoline-injected than from sham-injected animals. The data demonstrate in an in vivo paradigm, that activation of cholinergic pathways within the rat CNS stimulates arachidonic acid turnover in cerebral microvessels. This suggests a direct involvement of this fatty acid in second messenger function within microvessel endothelial cells and possibly attached pericytes. C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Williams, WM (reprint author), NIA, Neurosci Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 20 TC 5 Z9 5 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD APR PY 1998 VL 23 IS 4 BP 551 EP 555 DI 10.1023/A:1022490820109 PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA ZG668 UT WOS:000073027200014 PM 9566591 ER PT J AU Scortegagna, M Chikhale, E Hanbauer, I AF Scortegagna, M Chikhale, E Hanbauer, I TI Effect of lead on cytoskeletal proteins expressed in E14 mesencephalic primary cultures SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article DE lead; embryonic mesencephalic cultures; Pb-uptake; microtubule-associated proteins; GAP-43; serum-deprivation ID MICROTUBULE-ASSOCIATED PROTEINS; BLOOD-BRAIN-BARRIER; MESSENGER-RNA; RAT-BRAIN; DENDRITIC DEVELOPMENT; HIPPOCAMPAL-NEURONS; INORGANIC LEAD; GROWTH; GAP-43; METALLOTHIONEIN AB Several lints of evidence indicated that Pb exposure in vivo and in vitro altered neurite morphology in central and peripheral neurons. The present report shows that neurite length in mesencephalic primary cultures, consisting of neurons and glia, was decreased by Pb exposure when serum factors, presumably essential for glial functions, were absent in the culture medium. We studied whether a serum factor might control the mechanisms involved in the uptake and accumulation of Pb and its effect on cytoskeleton proteins. The total amount of Pb taken up in cell cultures was measured by atomic absorption spectroscopy and appeared to be down-regulated by a non-albumin-like serum component. In presence of serum, Pb exposure failed to alter cytoskeletal proteins. Instead, in serum-free neurobasal medium; Pb uptake failed to reach saturation within 6 h. Western blot analysis showed that the tau, 280 kDa MAP-2b, 70 kDa MAP-2c and GAP-43 protein bands were decreased 24 h after a 3 h exposure to 3 or 6 mu M Pb in absence of serum. However, if cultures were maintained in serum-containing media after a 3 h Pb exposure without serum, the immunoblots did not differ from those of controls. It can be inferred that a serum factor prevents cytoskeletal protein alterations by Pb. In serum free medium, Pb that is primarily scavenged by the metallothionein I/II isoforms present in glial cells, may bind to thiol residues of proteins involved in either oxidative stress response or transcriptional regulation of cytoskeletal proteins. Published by Elsevier Science Ltd. C1 NHLBI, Lab Mol Immunol, Bethesda, MD 20892 USA. NIA, Neurosci Lab, Bethesda, MD 20892 USA. RP NHLBI, Lab Mol Immunol, Bldg 10,Room 7N-312, Bethesda, MD 20892 USA. NR 40 TC 10 Z9 12 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 EI 1872-9754 J9 NEUROCHEM INT JI Neurochem. Int. PD APR PY 1998 VL 32 IS 4 BP 353 EP 359 DI 10.1016/S0197-0186(97)00101-0 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA ZK654 UT WOS:000073347000006 PM 9596558 ER PT J AU Fagan, SC Morgenstern, LB Petitta, A Ward, RE Tilley, BC Marler, JR Levine, SR Broderick, JP Kwiatkowski, TG Frankel, M Brott, TG Walker, MD AF Fagan, SC Morgenstern, LB Petitta, A Ward, RE Tilley, BC Marler, JR Levine, SR Broderick, JP Kwiatkowski, TG Frankel, M Brott, TG Walker, MD CA NINDS rt-PA Stroke Study Group TI Cost-effectiveness of tissue plasminogen activator for acute ischemic stroke SO NEUROLOGY LA English DT Article ID REHABILITATION; RECURRENCE; INFARCTION AB Tissue plasminogen activator (tPA) has been shown to improve 3-month outcome in stroke patients treated within 3 hours of symptom onset. The costs associated with this new treatment will be a factor in determining the extent of its utilization. Data from the NINDS rt-PA Stroke Trial and the medical literature were used to estimate the health and economic outcomes associated with using tPA in acute stroke patients, A Markov model was developed to estimate the costs per 1,000 patients eligible for treatment with tPA compared with the costs per 1,000 untreated patients. One-way and multiway sensitivity analyses (using Monte Carlo simulation) were performed to estimate the overall uncertainty of the model results. In the NINDS rt-PA Stroke Trial, the average length of stay was significantly shorter in tPA-treated patients than in placebo-treated patients (10.9 versus 12.4 days; p = 0.02) and more tPA patients were discharged to home than to inpatient rehabilitation or a nursing home (48% versus 36%; p = 0.002), The Markov model estimated an increase in hospitalization costs of $1.7 million and a decrease in rehabilitation costs of $1.4 million and nursing home cost of $4.8 million per 1,000 eligible treated patients for a health care system that includes acute through long-term care facilities, Multiway sensitivity analysis revealed a greater than 90% probability of cost savings. The estimated impact on long-term health outcomes was 564 (3 to 850) quality-adjusted life-years saved over 30 years of the model per 1,000 patients. Treating acute ischemic stroke patients with tPA within 3 hours of symptom onset improves functional outcome at 3 months and is likely to result in a net cost savings to the health care system. C1 Wayne State Univ, Coll Pharm, Dept Pharm Practice, Detroit, MI 48202 USA. Univ Texas, Dept Neurol, Austin, TX USA. Henry Ford Hlth Syst, Dept Pharm, Detroit, MI USA. Henry Ford Hlth Syst, Dept Neurol, Detroit, MI USA. Henry Ford Hlth Syst, Ctr Clin Effectiveness, Detroit, MI USA. Henry Ford Hlth Syst, Div Biostat & Res Epidemiol, Detroit, MI USA. NINDS, Div Stroke & Trauma, Bethesda, MD 20892 USA. Univ Cincinnati, Dept Neurol, Cincinnati, OH 45221 USA. Long Isl Jewish Med Ctr, Dept Emergency Med, New Hyde Park, NY USA. Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. RP Fagan, SC (reprint author), Wayne State Univ, Coll Pharm, Dept Pharm Practice, 1400 Chrysler, Detroit, MI 48202 USA. RI Fagan, Susan /D-3281-2009 FU NINDS NIH HHS [N01-NS-02382, N01-NS-02374, N01-NS-02377] NR 26 TC 243 Z9 246 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 1998 VL 50 IS 4 BP 883 EP 890 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA ZJ178 UT WOS:000073187300013 PM 9566367 ER PT J AU Berquin, PC Giedd, JN Jacobsen, LK Hamburger, SD Krain, AL Rapoport, JL Castellanos, FX AF Berquin, PC Giedd, JN Jacobsen, LK Hamburger, SD Krain, AL Rapoport, JL Castellanos, FX TI Cerebellum in attention-deficit hyperactivity disorder - A morphometric MRI study SO NEUROLOGY LA English DT Article ID POSITRON-EMISSION TOMOGRAPHY; BRAIN-DEVELOPMENT; CORPUS-CALLOSUM; BASAL GANGLIA; ANIMAL-MODEL; CHILDREN; MORPHOLOGY; VERMIS; DEGENERATION; ACTIVATION AB Clinical, neuroanatomic, neurobehavioral, and functional brain-imaging studies suggest a role for the cerebellum in cognitive functions, including attention. However, the cerebellum has not been systematically studied in attention-deficit hyperactivity disorder (ADHD). We quantified the cerebellar and vermal volumes, and the midsagittal areas of three vermal regions, from MRIs of 46 right-handed boys with ADHD and 47 matched healthy controls. Vermal volume was significantly less in the boys with ADHD. This reduction involved mainly the posterior inferior lobe (lobules VIII to X) but not the posterior superior lobe (lobules VI to VII). These results remained significant even after adjustment for brain volume and IQ. A cerebello-thalamo-prefrontal circuit dysfunction may subserve the motor control, inhibition, and executive function deficits encountered in ADHD. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. CHU, Hop Nord, Serv Pediat 1, Amiens, France. Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. RP Castellanos, FX (reprint author), 10 Ctr Dr,Room 3N202, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Roy, Amy/J-7613-2013; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 63 TC 335 Z9 346 U1 2 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 1998 VL 50 IS 4 BP 1087 EP 1093 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA ZJ178 UT WOS:000073187300045 PM 9566399 ER PT J AU Mancardi, GL Sardanelli, F Parodi, RC Melani, E Capello, E Inglese, M Ferrari, A Sormani, MP Ottonello, C Levrero, F Uccelli, A Bruzzi, P AF Mancardi, GL Sardanelli, F Parodi, RC Melani, E Capello, E Inglese, M Ferrari, A Sormani, MP Ottonello, C Levrero, F Uccelli, A Bruzzi, P TI Effect of copolymer-1 on serial gadolinium-enhanced MRI in relapsing remitting multiple sclerosis SO NEUROLOGY LA English DT Article; Proceedings Paper CT 121st Annual Meeting of the American-Neurological-Association CY OCT 13-16, 1996 CL MIAMI, FLORIDA SP Amer Neurol Assoc ID RESONANCE-IMAGING LESIONS; PLACEBO-CONTROLLED TRIAL; DISEASE-ACTIVITY; DOUBLE-BLIND; MULTICENTER; GUIDELINES; DISABILITY AB We examined the effect of Copolymer-1 (Cop1) on magnetic resonance (MR) imaging changes in 10 patients with relapsing-remitting multiple sclerosis (RRMS). Monthly gadolinium (Gd)-enhanced MR imaging was performed for 9 to 27 months in the pretreatment period followed by 10 to 14 additional months during Cop1 treatment. MR images were evaluated by two radiologists (F.S. and R.C.P.) masked to the scan date. We found a 57% decrease in the frequency of new Gd-enhancing lesions and in the mean area/month of new Gd-enhancing lesions in the Cop1 treatment period compared with the pretreatment period (0.92 versus 2.20 lesions per month and 22 mm(2) versus 43 mm(2) area/month; p = 0.1, Wilcoxon signed rank test). Percentage change in lesion load area on T2-weighted images showed a decrease in the accumulation of lesion area during treatment, which was significant for the patient group with a longer pretreatment period (p = 0.05, Friedman test). These results demonstrate a reduction in the number of new Gd-enhancing lesions and in the lesion load during Cop1 treatment compared with the preceding period without therapy and are suggestive of an effect of Cop1 on MR abnormalities observed in multiple sclerosis. C1 Univ Genoa, Dept Neurol Sci, I-16132 Genoa, Italy. Univ Genoa, Inst Radiol, I-16132 Genoa, Italy. S Martino Hosp, Genoa, Italy. Natl Canc Inst, Unit Clin Epidemiol & Trials, Genoa, Italy. RP Mancardi, GL (reprint author), Univ Genoa, Dept Neurol Sci, Via Toni 5, I-16132 Genoa, Italy. RI Sardanelli, Francesco/M-2917-2016; mancardi, giovanni luigi/K-8656-2016; OI Sardanelli, Francesco/0000-0001-6545-9427; mancardi, giovanni luigi/0000-0001-8427-118X; Bruzzi, Paolo/0000-0002-7874-2077 NR 26 TC 82 Z9 82 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 1998 VL 50 IS 4 BP 1127 EP 1133 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA ZJ178 UT WOS:000073187300052 PM 9566406 ER PT J AU Gershon, ES Badner, JA Goldin, LR Sanders, AR Cravchik, A Detera-Wadleigh, SD AF Gershon, ES Badner, JA Goldin, LR Sanders, AR Cravchik, A Detera-Wadleigh, SD TI Closing in on genes for manic-depressive illness and schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Review DE genetics; bipolar illness; depressive disorder; schizophrenia; genetic linkage; genotypes; linkage disequilibrium; dopamine receptors; chromosome 6; chromosome 18; chromosome 21; event-related potentials ID BIPOLAR AFFECTIVE-DISORDER; GENETICALLY COMPLEX TRAITS; CHROMOSOME-18 DNA MARKERS; GENOME-WIDE SEARCH; RECEPTOR GENE; SUSCEPTIBILITY GENE; LINKAGE ANALYSIS; SAMPLING CONSIDERATIONS; VULNERABILITY LOCUS; ASSOCIATION AB Advances in the human genetic map, and in genetic analysis of linkage and association in complex inheritance traits, have led to genetic progress in the major psychoses. For chromosome 6 in schizophrenia, and chromosomes 18 and 21 in manic-depressive illness, there are reports of linkage in several independent data sets. These are small effect genes, best detected with affected-relative-pair linkage methods. Association with candidate genes is an alternative strategy to uncovering susceptibility genes for these illnesses, but convincing associations remain to be demonstrated. New clinical and laboratory investigation methods are being developed. Testing every gene in the human genome for association with illness has recently been proposed (Risch and Merikangas 1996). This would require further progress in characterizing the genome and in automated large-scale genotyping. The best type of pedigree sampling for common disease studies, whether for linkage or association, is not yet established. An endophenotype hybrid strategy can combine genetic linkage, association, and pathophysiologic studies. As clinical molecular investigation methods advance, identification of disease susceptibility mutations and delineation of their pathophysiological roles may be expected. Published by Elsevier Science Inc. C1 NIMH, Clin Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Gershon, ES (reprint author), NIMH, Clin Neurogenet Branch, NIH, Bldg 10,Room 3N218, Bethesda, MD 20892 USA. NR 64 TC 36 Z9 40 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD APR PY 1998 VL 18 IS 4 BP 233 EP 242 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA YX689 UT WOS:000072066700001 PM 9509491 ER PT J AU Liu, X Matochik, JA Cadet, JL London, ED AF Liu, X Matochik, JA Cadet, JL London, ED TI Smaller volume of prefrontal lobe in polysubstance abusers: A magnetic resonance imaging study SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE prefrontal lobe; MRI; substance abuse ID COCAINE ABUSERS; DISORDERS; CONSEQUENCES; DYSFUNCTION; ADOLESCENTS; ALCOHOLISM; DAMAGE; CORTEX; SPECT; BOYS AB The present study was conducted to test the hypothesis that individuals with substance abuse disorder exhibit structural deficits in the prefrontal cortex. Volumes of the prefrontal lobe in subjects with histories of polysubstance abuse (n = 25) were measured and compared with those in normal volunteers (n = 14), using high-resolution volumetric magnetic resonance imaging (MRI). The research participants were men, 22 to 41 years of age. Polysubstance abusers were abstinent from drugs of abuse (except nicotine) for at least 15 days before MRI scanning. The total volumes of the prefrontal lobe (left and right hemispheres) were significantly smaller in the substance abuse group than in the control group. When the prefrontal lobe was segmented for gray and white matter, the deficit in the substance abusers was seen as significantly smaller volumes of gray but not of white matter. These results indicate that hypoplasia and/or atrophy in the prefrontal cortex accompany substance abuse and suggest that structural deficits in the prefrontal cortex may play an essential role in the neuropathological basis of functional impairments in substance abuse disorder, as demonstrated by functional brain imaging and cognitive studies. Published by Elsevier Science Inc. C1 NIDA, Brain Imaging Ctr, Intramural Res Program, Neurosci Branch, Baltimore, MD 21224 USA. RP London, ED (reprint author), NIDA, Brain Imaging Ctr, Intramural Res Program, Neurosci Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 34 TC 96 Z9 99 U1 7 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD APR PY 1998 VL 18 IS 4 BP 243 EP 252 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA YX689 UT WOS:000072066700002 PM 9509492 ER PT J AU Hansson, SR Mezey, E Hoffman, BJ AF Hansson, SR Mezey, E Hoffman, BJ TI Serotonin transporter messenger RNA in the developing rat brain: Early expression in serotonergic neurons and transient expression in non-serotonergic neurons SO NEUROSCIENCE LA English DT Article DE antidepressants; cocaine; in situ hybridization histochemistry; sensory pathways; tryptophan hydroxylase; vesicular monoamine transporter ID FLUORESCENCE HISTOCHEMICAL OBSERVATIONS; DEPENDENT SYNAPTIC PLASTICITY; CENTRAL MONOAMINE NEURONS; CENTRAL-NERVOUS-SYSTEM; GROWTH CONE MOTILITY; SOMATOSENSORY CORTEX; NEUROTRANSMITTER TRANSPORTERS; CINGULATE CORTEX; CEREBRAL-CORTEX; CRITICAL PERIOD AB Serotonin has been shown to affect the development of the mammalian nervous system. The serotonin transporter is a major factor in regulating extracellular serotonin levels. Using in situ hybridization histochemistry the rat serotonin transporter messenger RNA was localized during embryogenesis, the first four weeks postnatally and adulthood. Three general classes of serotonin transporter messenger RNA expression patterns were observed: (i) early detection with continued expression through adult age, (ii) transient expression colocalized with vesicular monoamine transporter 2 messenger RNA but with no detectable tryptophan hydroxylase immunoreactivity, and (iii) transient expression in the apparent absence of both vesicular monoamine transporter 2 messenger RNA and tryptophan hydroxylase immunoreactivity. For example, hybridization for serotonin transporter messenger RNA was strong in serotonin cell body-containing areas beginning early in gestation, and remained intense through adulthood. Immunoreactivity for tryptophan hydroxylase, the rate-limiting enzyme in serotonin synthesis, was completely overlapping with the presence of serotonin transporter messenger RNA in raphe nuclei postnatally. Sensory relay systems including the ventrobasal nucleus (somatosensory), lateral and medial geniculate nuclei (visual and auditory, respectively) as well as trigeminal, cochlear and solitary nuclei were representative of the second class of observations. In general: the limbic system expressed serotonin transporter messenger RNA in the third pattern with various limbic structures differing in the timing of expression. Septum, olfactory areas and the developing hippocampus contained serotonin transporter messenger RNA early in the developing brain. Other regions such Is cingulate and frontopolar cortex exhibited hybridization peri-and postnatally, respectively Several hypothalamic nuclei and pituitary transiently expressed serotonin transporter messenger RNA either postnatally or perinatally, respectively. If the observed patterns correlate with functional protein expression, distinct classes of serotonin transporter messenger RNA expression may reflect different functional roles for the serotonin transporter and serotonin, itself. Since the serotonin transporter is a target for a number of addictive substances including cocaine and amphetamine derivatives as well as antidepressants, transient expression of the serotonin transporter might suggest a window of vulnerability of associated cells to fetal drug exposure. Re-uptake, storage and re-release from non-serotonergic neurons might serve as a feedback mechanism from target neurons to serotonergic neurons. Alternatively, the transient expression of serotonin transporter messenger RNA mag reflect critical periods important for right regulation of extracellular serotonin in several brain regions, and may indicate previously unappreciated roles for serotonin as a developmental cue. (C) 1998 IBRO. Published by Elsevier Science Ltd. C1 NIMH, Unit Mol Pharmacol, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. NINDS, Basic Neurosci Program, Bethesda, MD 20892 USA. RP Hoffman, BJ (reprint author), NIMH, Unit Mol Pharmacol, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. NR 91 TC 118 Z9 121 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD APR PY 1998 VL 83 IS 4 BP 1185 EP 1201 DI 10.1016/S0306-4522(97)00444-2 PG 17 WC Neurosciences SC Neurosciences & Neurology GA YW574 UT WOS:000071950000018 PM 9502257 ER PT J AU Savory, J Huang, Y Wills, MR Herman, MM AF Savory, J Huang, Y Wills, MR Herman, MM TI Reversal by desferrioxamine of tau protein aggregates following two days of treatment in aluminum-induced neurofibrillary degeneration in rabbit: Implications for clinical trials in Alzheimer's disease SO NEUROTOXICOLOGY LA English DT Article DE neurofibrillary aggregates; reversal by DFO; short-term therapy; aluminum; tau AB \A clinical trial in patients with Alzheimer's disease has indicated that frequent intramuscular (i.m.) treatment with desferrioxamine (DFO) slows progression of the disease. Confirmatory trials have not been carried out, partly because of the rigors of twice daily intramuscular injections over a period of 2 years, even though the initial report gave promising results. The aim of the present study was to determine an optimal DFO treatment protocol in an animal model exhibiting Alzheimer's-like intraneuronal protein aggregates, previously shown to be partially reversed by such treatment. New Zealand white rabbits were injected intracisternally with either aluminum (Al) maltolate or with saline on day 0. Intramuscular injections of DFO were given to selected rabbits for 2 days prior to sacrifice on days 4, 6 or 8. Bielschowssky's silver impregnation demonstrated widespread neurofibrillary degeneration (NFD) in neuronal cell bodies and neurites of brain and spinal cord from Al-treated rabbits. Monoclonal antibodies Tau-2 AT8, PHF-I and Alz-50, all of which characteristically stain neurofibrillary tangles associated with Alzheimer's disease, strongly labeled the Al-induced NFD. The number of positive neurons and staining intensities were much less in rabbits treated with Al and subsequently with DFO, than in animals only given Al. Control rabbits receiving intracisternal saline were negative for NFD. The results of quantitative immunohistochemistry using image analysis confirmed that immunostaining densities with all tau mAbs were higher in Al-treated than in Al-DFO-treated or in saline-treated controls. Furthermore, it appears that hyperphosphorylation of tau does not make this protein resistant to degradation once Al has been removed by DFO treatment. The effectiveness of only two days of DFO treatment in reversing Al-induced neurofibrillary degeneration suggests that further clinical trials of DFO for treatment of Alzheimer's disease should be attempted using much less frequent administration of DFO than in the initial study. (C) 1998 Intox Press, Inc. C1 Univ Virginia, Hlth Sci Ctr, Dept Pathol, Charlottesville, VA 22908 USA. Univ Virginia, Hlth Sci Ctr, Dept Internal Med, Charlottesville, VA 22908 USA. Univ Virginia, Hlth Sci Ctr, Dept Biochem, Charlottesville, VA 22908 USA. NIMH, Neurosci Ctr St Elizabeths, IRP, Clin Brain Disorders Branch,Neuropathol Sect,NIH, Washington, DC USA. RP Savory, J (reprint author), Univ Virginia, Hlth Sci Ctr, Dept Pathol, Box 168, Charlottesville, VA 22908 USA. NR 16 TC 34 Z9 35 U1 0 U2 1 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 USA SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD APR PY 1998 VL 19 IS 2 BP 209 EP 214 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA ZE075 UT WOS:000072755200004 PM 9553957 ER PT J AU Eckelman, WC AF Eckelman, WC TI Sensitivity of new radiopharmaceuticals SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Review DE radiopharmaceutical development; sensitivity; PET; SPECT ID POSITRON EMISSION TOMOGRAPHY; RECEPTOR-BINDING RADIOTRACERS; IN-VIVO; GALACTOSYL-NEOGLYCOALBUMIN; 3-QUINUCLIDINYL BENZILATE; ESTROGEN-RECEPTORS; BRAIN; PET; INVIVO; COMPETITION C1 NIH, Ctr Clin, PET Dept, Bethesda, MD 20892 USA. RP Eckelman, WC (reprint author), NIH, Ctr Clin, PET Dept, Bldg 10,Rm 1C495,10 Ctr Dr,MSC 1180, Bethesda, MD 20892 USA. NR 52 TC 43 Z9 43 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD APR PY 1998 VL 25 IS 3 BP 169 EP 173 DI 10.1016/S0969-8051(97)00207-2 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZE898 UT WOS:000072842700001 PM 9620619 ER PT J AU John, CS Gulden, ME Li, JH Bowen, WD McAfee, JG Thakur, ML AF John, CS Gulden, ME Li, JH Bowen, WD McAfee, JG Thakur, ML TI Synthesis, in vitro binding, and tissue distribution of radioiodinated 2-[I-125]N-(N-benzylpiperidin-4-yl)-2-iodo benzamide, 2-[I-125]BP: A potential sigma receptor marker for human prostate tumors SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of The Society-for-Nuclear-Medicine CY JUN 02-06, 1996 CL DENVER, COLORADO SP Soc Nucl Med DE sigma receptors; prostate cancer; non-invasive imaging; radioiodinated ligand ID CELL LUNG-CARCINOMA; AFFINITY; LIGAND; MELANOMA; CANCER AB The preclinical evaluation of a a receptor-specific radiopharmaceutical that binds to human prostate tumor cells with a high affinity is described. We have synthesized and radioiodinated 2-[I-125]-N-(N-benzylpiperidin-4-yl)-2-iodobenzamide (2-[I-125]BP) that possesses high affinity for both sigma-1 and sigma-2 receptor subtypes that are expressed on a variety of tumor cells. 2-IBP was synthesized, purified and characterized by routine spectroscopic and analytical methods. Radioiodination was accomplished using an oxidative iododestannylation reaction in the presence of chloramine T in high yields (76%-93%) with a very high-specific activity (1700-1900 Ci/mmol). The in vitro competition binding studies of 2-[I-125]BP with various a receptor ligands in LnCAP human prostate tumor cells showed a dose dependent saturable binding. The inhibition constants (K-i, nM) for binding of 2-[I-125]BP to human prostate tumor cells for 4-IBP, haloperidol and 2-IBP were 4.09, 6.34 and 1.6 nM, respectively. The clearance of 2-[I-125]BP, in Sprague-Dawley rats, was rapid from the blood pool, other normal tissues and the total body. Tissue distribution studies in nude mice bearing human prostate tumor (DU-145) also showed a fast clearance from normal organs. The tumor had the highest percentage of injected dose per gram (%ID/g) of all tissues at 4 h as well as 24 h (2.0 +/- 0.05 and 0.147 +/- 0.038 ID/g, respectively) postinjection. The in vivo receptor binding specificity was demonstrated using haloperidol (a known high affinity a receptor ligand). A significant decrease (>50%, p = 0.001) was observed in tumor concentration when haloperidol was used as a blocking agent. The high affinity of 2-[I-125]BP for a receptor-binding sites, its fast in vivo clearance from normal organs and its high uptake and retention in tumor implies that 2-[I-123]BP pr 2-[I-131]BP may be a promising tracer for noninvasive imaging of human prostate tumors. (C) 1998 Elsevier Science Inc. C1 George Washington Univ, Med Ctr, Radiopharmaceut Chem Sect, Dept Radiol, Washington, DC 20037 USA. Thomas Jefferson Univ Hosp, Dept Radiol, Philadelphia, PA 19107 USA. NIDDKD, Unit Receptor Biochem & Pharmacol, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP John, CS (reprint author), George Washington Univ, Med Ctr, Radiopharmaceut Chem Sect, Dept Radiol, 2300 I St NW,661 Ross Hall, Washington, DC 20037 USA. FU NCI NIH HHS [CA58496] NR 24 TC 26 Z9 28 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD APR PY 1998 VL 25 IS 3 BP 189 EP 194 DI 10.1016/S0969-8051(97)00168-6 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZE898 UT WOS:000072842700004 PM 9620622 ER PT J AU Gorbalenya, AE AF Gorbalenya, AE TI Non-canonical inteins SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GROUP-I INTRONS; PROTEIN SPLICING ELEMENTS; HIDDEN MARKOV-MODELS; AMINO-ACID-SEQUENCE; RECOMMENDED NOMENCLATURE; ADENOSINE-TRIPHOSPHATASE; SACCHAROMYCES-CEREVISIAE; CATALYTIC SUBUNIT; GENE CONVERSION; ALIGNMENT AB Previous analyses have shown that inteins (protein splicing elements) employ two structural organizations: the 'canonical' Nintein-Dod-inteinC found in dozens of inteins and a 'non-canonical' Nintein-inteinC described in two inteins, where Nintein at the N-terminus and inteinC at the C-terminus are conserved domains involved in self-splicing and Dod is the Dod DNA endonuclease (DNase). In this study, four-non-canonical inteins, each with unique structural features, have been identified using alignment-based Hidden Markov Models. A Nintein-inteinC intein, carrying an unprecedented replacement of the N-terminal catalytic Cys(Ser) by Ara, is described in a putative ATPase encoded by Methanococcus jannaschii. Three replicative proteins of Synechocystis spp. contain inteins with the organizations: (i) Nintein - X - inteinC/Dod, where X is an uncharacterized domain and Dod DNase is located in an alternative open reading frame (ORF) being embedded between two novel CG and YK domains; (ii) Nintein-HN-inteinC, where HN stands for phage-like DNase from the EX1H-HX3H family; (iii) Nintein>\\< indicates that the intein domains are associated with a disrupted host protein encoded by two spatially separated ORFs. The expression of some of these newly identified inteins may affect the intein hosts. The variety of structural forms of inteins could have evolved through invasion of self-splicing proteases by different mobile DNases or the departure of mobile DNases from canonical inteins. C1 Russian Acad Med Sci, MP Chumakov Inst Poliomyel & Viral Encephal, Moscow 142782, Russia. Leiden Univ, Med Ctr, Dept Virol, NL-2300 RC Leiden, Netherlands. RP Gorbalenya, AE (reprint author), NCI, Frederick Biomed Supercomp Ctr, SAIC, FCRDC, POB B,Bldg 430, Frederick, MD 21702 USA. EM gorbalen@ncifcrf.gov RI Gorbalenya, Alexander/J-4818-2012 OI Gorbalenya, Alexander/0000-0002-4967-7341 NR 64 TC 39 Z9 44 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR 1 PY 1998 VL 26 IS 7 BP 1741 EP 1748 DI 10.1093/nar/26.7.1741 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZH038 UT WOS:000073065900025 PM 9512547 ER PT J AU Cerritelli, SM Fedoroff, OY Reid, BR Crouch, RJ AF Cerritelli, SM Fedoroff, OY Reid, BR Crouch, RJ TI A common 40 amino acid motif in eukaryotic RNases H1 and caulimovirus ORF VI proteins binds to duplex RNAs SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DOUBLE-STRANDED-RNA; CAULIFLOWER MOSAIC-VIRUS; COLI RIBONUCLEASE-H; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; KINASE-DAI; REVERSE-TRANSCRIPTASE; DROSOPHILA STAUFEN; DOMAIN; SEQUENCE AB Eukaryotic RNases H from Saccharomyces cerevisiae, Schizosaccharomyces pombe and Crithidia fasciculata, unlike the related Escherichia coli RNase HI, contain a non-RNase H domain with a common motif, Previously we showed that S.cerevisiae RNase H1 binds to duplex RNAs (either RNA-DNA hybrids or double-stranded RNA) through a region related to the double-stranded RNA binding motif, A very similar amino acid sequence is present in caulimovirus ORF VI proteins. The hallmark of the RNase H/caulimovirus nucleic acid binding motif is a stretch of 40 amino acids with 11 highly conserved residues, seven of which are aromatic. Point mutations, insertions and deletions indicated that integrity of the motif is important for binding. However, additional amino acids are required because a minimal peptide containing the motif was disordered in solution and failed to bind to duplex RNAs, whereas a longer protein bound well. Schizosaccharomyces pombe RNase H1 also bound to duplex RNAs, as did proteins in which the S. cerevisiae RNase H1 binding motif was replaced by either the C. fasciculata or by the cauliflower mosaic virus ORF VI sequence. The similarity between the RNase H and the caulimovirus domain suggest a common interaction with duplex RNAs of these two different groups of proteins. C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. Univ Washington, Dept Chem, Seattle, WA 98195 USA. Univ Washington, Dept Biochem, Seattle, WA 98195 USA. RP Crouch, RJ (reprint author), NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RI Fedorov, Oleg/B-6412-2014 OI Fedorov, Oleg/0000-0001-9004-1815 NR 38 TC 38 Z9 38 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR 1 PY 1998 VL 26 IS 7 BP 1834 EP 1840 DI 10.1093/nar/26.7.1834 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZH038 UT WOS:000073065900038 PM 9512560 ER PT J AU Bridson, PK Lin, X Melman, N Ji, XD Jacobson, KA AF Bridson, PK Lin, X Melman, N Ji, XD Jacobson, KA TI Synthesis and adenosine receptor affinity of 7-beta-D-ribofuranosylxanthine SO NUCLEOSIDES & NUCLEOTIDES LA English DT Article ID RAT-BRAIN; DERIVATIVES AB 7-beta-D-Ribofuranosylxanthine, a previously unreported isomer of xanthosine, was prepared in four steps from 7-benzylxanthine. The procedure, which involves the use of pivaloyloxymethyl groups to protect the xanthine ring, was also applied to preparation of some 1-N-alkyl derivatives of 7-ribosylxanthine. Adenosine receptor affinity for these compounds was determined. 7-beta-D-Ribofuranosylxanthine was found to have higher affinity and greater selectivity for the A(1) receptor than previously reported xanthine nucleosides, and to be a partial agonist. C1 Univ Memphis, Dept Chem, Memphis, TN 38152 USA. NIDDKD, Bioorgan Chem Lab, Mol Recognit Sect, Bethesda, MD 20892 USA. RP Bridson, PK (reprint author), Univ Memphis, Dept Chem, Memphis, TN 38152 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 14 TC 2 Z9 2 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0732-8311 J9 NUCLEOS NUCLEOT JI Nucleosides Nucleotides PD APR PY 1998 VL 17 IS 4 BP 759 EP 768 DI 10.1080/07328319808004673 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZD803 UT WOS:000072726000005 PM 9708335 ER PT J AU Spong, CY Ghidini, A Dildy, GA Loucks, CA Varner, MW Pezzullo, JC AF Spong, CY Ghidini, A Dildy, GA Loucks, CA Varner, MW Pezzullo, JC TI Elevated second-trimester maternal serum hCG: A marker of inadequate angiogenesis SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID HUMAN CHORIONIC-GONADOTROPIN; FETAL GROWTH; ASSOCIATION; TROPHOBLAST; HYPOXIA; RELEASE; INTERLEUKIN-6; IL-6 AB Objective: To measure angiogenin, a potent inducer of neovascularization and interleukin-6, as an indicator of acute inflammation, in second-trimester amniotic fluid of patients with elevated maternal serum hCG. Methods: In this case-control study, 20 patients with elevated maternal serum hCG (at least 2.0 multiples of median) at triple screen were matched 2:1 with controls on the basis of year of amniocentesis, parity, and race. Inclusion criteria were 1) singleton gestation, 2) no evidence of anomalies, and 3) genetic amniocentesis. Amniotic fluid was immunoassayed for angiogenin and interleukin-6. The immunoassay sensitivity for angiogenin was 0.026 ng/mL, interassay coefficient of variation 4.6%, and intra-assay coefficient of variation 2.9%. For interleukin-6, the immunoassay sensitivity was 2.37 pg/mL, interassay coefficient of variation 2.7%, and intra-assay coefficient of variation 1.9%. Angiogenin and interleukin-6 values were normalized by using natural log transformation for statistical analysis. Statistical analysis included analysis of variance and stepwise regression, with P < .05 significant. Results: After correcting (by multivariate regression) for gestational age at sampling and nulliparity, amniotic fluid angiogenin levels were significantly lower in the study subjects than in controls (26% +/- 11% lower, P = .004), whereas the interleukin-6 levels did not change significantly (34% +/- 40% lower, P = .3). Conclusion: Amniotic fluid angiogenin levels are significantly lower in patients with elevated maternal serum hCG at triple screen, suggesting inadequate angiogenesis, but interleukin-6 values do not differ significantly. (C) 1998 by The American College of Obstetricians and Gynecologists. C1 NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Obstet & Gynecol, Washington, DC USA. Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. RP Spong, CY (reprint author), NICHD, Dev Neurobiol Lab, NIH, Bldg 49,Room 5A-38,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Varner, Michael/K-9890-2013 OI Varner, Michael/0000-0001-9455-3973 NR 14 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 1998 VL 91 IS 4 BP 605 EP 608 DI 10.1016/S0029-7844(98)00010-6 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA ZD973 UT WOS:000072744300024 PM 9540950 ER PT J AU Kupfer, C AF Kupfer, C TI Outcomes research - Translating efficacy into effectiveness SO OPTOMETRY AND VISION SCIENCE LA English DT Editorial Material C1 NEI, NIH, Bethesda, MD 20892 USA. RP Kupfer, C (reprint author), NEI, NIH, Bethesda, MD 20892 USA. NR 4 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-5488 EI 1538-9235 J9 OPTOMETRY VISION SCI JI Optom. Vis. Sci. PD APR PY 1998 VL 75 IS 4 BP 235 EP 236 DI 10.1097/00006324-199804000-00001 PG 2 WC Ophthalmology SC Ophthalmology GA ZJ875 UT WOS:000073262500001 PM 9586746 ER PT J AU Nakhasi, HL Pogue, GP Duncan, RC Joshi, M Atreya, CD Lee, NS Dwyer, DM AF Nakhasi, HL Pogue, GP Duncan, RC Joshi, M Atreya, CD Lee, NS Dwyer, DM TI Implications of calreticulin function in parasite biology SO PARASITOLOGY TODAY LA English DT Article ID CELL-SURFACE CALRETICULIN; CALCIUM-BINDING PROTEIN; MOLECULAR CHAPERONE; LEISHMANIA; ANTIGEN; LECTIN; GENE; CA2+; OVEREXPRESSION; AUTOANTIGEN AB Calreticulin (CR) is it Ca2+-binding, multifunctional protein. The amazing array of CX-associated functions range from intracellular activities in secondary messenger release, protein folding and the modulation of gene expression to potential interactions with host receptors and signaling machinery and recognition by the host immune system. The multifunctional nature of CA may impact upon the ability of cells to recognize extracellular stimuli and coordinate appropriate responses. Identification of CX isolated from parasites and the conservation of its functions suggests that investigations into the contributions of CA to various aspects of parasite biology should be undertaken because it may reveal information regarding parasite interaction with the host and how the parasite may modulate its response to the host. C1 US FDA, Sect Viral Pathogenesis & Adverse React, Div Viral Prod, OVRR,CBER, Bethesda, MD 20892 USA. NIAID, Cell Biol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Biosource Technol, Vacaville, CA 95688 USA. RP Nakhasi, HL (reprint author), US FDA, Sect Viral Pathogenesis & Adverse React, Div Viral Prod, OVRR,CBER, Bethesda, MD 20892 USA. RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 NR 32 TC 33 Z9 36 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD APR PY 1998 VL 14 IS 4 BP 157 EP 160 DI 10.1016/S0169-4758(97)01180-0 PG 4 WC Parasitology SC Parasitology GA ZD176 UT WOS:000072659000011 PM 17040734 ER PT J AU Etzel, RA Balk, SJ Bearer, CF Miller, MD Shannon, MW Shea, KM Falk, H Goldman, LR Miller, RW Rogan, W Coven, B Fedeyko, HJ AF Etzel, RA Balk, SJ Bearer, CF Miller, MD Shannon, MW Shea, KM Falk, H Goldman, LR Miller, RW Rogan, W Coven, B Fedeyko, HJ TI Toxic effects of indoor molds SO PEDIATRICS LA English DT Article ID AIR AB This statement describes molds, their toxic properties, and their potential for causing toxic respiratory problems in infants. Guidelines for pediatricians are given to help reduce exposures to mold in homes of infants. This is a rapidly evolving area and more research is ongoing. C1 Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. US EPA, Washington, DC 20460 USA. NCI, Bethesda, MD 20892 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Etzel, RA (reprint author), Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. RI Goldman, Lynn/D-5372-2012; OI Miller, Mark/0000-0002-9301-0093 NR 21 TC 35 Z9 35 U1 0 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 1998 VL 101 IS 4 BP 712 EP 714 PG 3 WC Pediatrics SC Pediatrics GA ZE903 UT WOS:000072843200043 ER PT J AU Etzel, RA Balk, SJ Bearer, CF Miller, MD Shea, KM Simon, PR AF Etzel, RA Balk, SJ Bearer, CF Miller, MD Shea, KM Simon, PR CA Amer Acad Pediat TI Risk of ionizing radiation exposure to children: A subject review SO PEDIATRICS LA English DT Review ID INDUCED THYROID-CANCER; ATOMIC-BOMB SURVIVORS; BREAST-CANCER; EXTERNAL RADIATION; CHILDHOOD; CHERNOBYL; HISTORY; TUMORS; BRAIN AB Exposure of children to ionizing radiation most commonly is from the environment, chiefly through cosmic rays and radon, or from medical technology. Medical radiation exposure occurs during diagnosis, therapy, and dental radiography. More is known about the biological effects of exposure to ionizing radiation than to nonionizing radiation from microwaves, radiowaves, and the electrical fields of other electrical appliances. This review applies only to sources of ionizing radiation and does not include the potential risks of indoor radon. The effects on children of ionizing radiation have been studied from war activities and environmental accidents. Projections are made from that data to help pediatricians evaluate risk from radiation when ordering radiographs. C1 Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. NCI, Bethesda, MD 20892 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Etzel, RA (reprint author), Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. OI Miller, Mark/0000-0002-9301-0093 NR 34 TC 27 Z9 28 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 1998 VL 101 IS 4 BP 717 EP 719 PG 3 WC Pediatrics SC Pediatrics GA ZE903 UT WOS:000072843200045 ER PT J AU Katcher, ML Agran, P Laraque, D Pollack, SH Smith, BL Smith, GA Spivak, HR Tully, SR Anderson, SJ Griesemer, B Johnson, MD McLain, LG Rowland, TW Small, E AF Katcher, ML Agran, P Laraque, D Pollack, SH Smith, BL Smith, GA Spivak, HR Tully, SR Anderson, SJ Griesemer, B Johnson, MD McLain, LG Rowland, TW Small, E CA Amer Acad Pediat TI In-line skating injuries in children and adolescents SO PEDIATRICS LA English DT Article AB In-line skating has become one of the fastest-growing recreational sports in the United States. Recent studies emphasize the value of protective gear in reducing the incidence of injuries. Recommendations are provided for parents and pediatricians, with special emphasis on the novice or inexperienced skater. C1 NICHHD, Bethesda, MD 20892 USA. US Dept Transportat, Washington, DC 20590 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Canadian Paediat Soc, Ottawa, ON, Canada. Natl Athlet Trainers Assoc, Dallas, TX 75247 USA. RP Katcher, ML (reprint author), NICHHD, Bethesda, MD 20892 USA. NR 11 TC 22 Z9 22 U1 0 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 1998 VL 101 IS 4 BP 720 EP 722 PG 3 WC Pediatrics SC Pediatrics GA ZE903 UT WOS:000072843200046 ER PT J AU Nilius, B Prenen, J Voets, T Eggermont, J Bruzik, KS Shears, SB Droogmans, G AF Nilius, B Prenen, J Voets, T Eggermont, J Bruzik, KS Shears, SB Droogmans, G TI Inhibition by inositoltetrakisphosphates of calcium- and volume-activated Cl- currents in macrovascular endothelial cells SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE endothelium; patch clamp; volume-activated chloride current; Ins(1,4,5,6)P-4; Ins(3,4,5,6)P-4; Ins(1,3,4,5,6)P-5 ID CHLORIDE CHANNELS; INTRACELLULAR CALCIUM; RAT-LIVER; MESSENGERS; SECRETION; MEMBRANE; AGONISTS AB We have used the whole-cell patch-clamp technique to study the effects of inositol 1,4,5,6-tetrakisphosphate [Ins(1,4,5,6)P-4], inositol 3,4,5,6-tetrakisphosphate [Ins(3,4,5,6)P-4] and inositol 1,3,4,5,6-pentacis-phosphate [Ins(1,3,4,5,6)P-5] on volume-activated Cl- currents (I-Cl,I-vol) in cultured endothelial cells from bovine pulmonary artery (CPAE cells). Ins(1,4,5,6)P-4 and Ins(3,4,5,6)P-4 were applied intracellularly via the patch pipette at concentrations between 10 and 100 mu M Both tetrakisphosphates inhibited the Cl- current I-Cl,I-Ca, which was activated by intracellular loading of the cells with 500 nM Ca2+ [for inhibition by Ins(1,4,5,6)P-4: 58% at 10 mu M, 75% at 100 mu M; for Ins(3,4,5,6)P-4: 44% at 10 mu M, 65% at 100 mu M] Inhibition of I-Cl,I-Ca occurred without significant changes in its kinetic properties. The amplitude of I-Cl,I-vol activated by a 13.5 or 27% hypotonic solution at +100 mV was strongly reduced in cells loaded with either tetrakisphosphate, i.e. a 73% reduction for Ins(3,4,5,6)P-4 and 89% for Ins(1,4,5,6)P-4 at 100 mu M. Both tetrakisphosphates also inhibited a current probably identical to I-Cl,I-vol which was activated by dialysing the cell with 100 mu M guanosine 5'-O-(3-thiotriphosphate) (GTP[gamma-g). Ins(1,3,4,5,6)P-5 at a concentration of 30 mu M did not significantly reduce I-Cl,I-vol. The effects of Ins(3,4,5,6)P-4 may represent an inhibitory pathway for the I-Cl,I-Ca and I-Cl,I-vol in macrovascular endothelium after sustained receptor-mediated activation of phospholipase C. C1 Catholic Univ Louvain, Fysiol Lab, B-3000 Louvain, Belgium. NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. RP Nilius, B (reprint author), Catholic Univ Louvain, Fysiol Lab, Campus Gasthuisberg, B-3000 Louvain, Belgium. RI Voets, Thomas/E-2466-2012 OI Voets, Thomas/0000-0001-5526-5821 NR 37 TC 22 Z9 22 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD APR PY 1998 VL 435 IS 5 BP 637 EP 644 DI 10.1007/s004240050564 PG 8 WC Physiology SC Physiology GA ZB765 UT WOS:000072505700007 PM 9479016 ER PT J AU Long, RM AF Long, RM TI News from the National Institute of General Medical Sciences (NIGMS) SO PHARMACEUTICAL RESEARCH LA English DT News Item C1 NIGMS, Pharmacol & Physiol Sci Branch, Div Pharmacol Physiol & Biol Chem, NIH, Bethesda, MD 20892 USA. RP Long, RM (reprint author), NIGMS, Pharmacol & Physiol Sci Branch, Div Pharmacol Physiol & Biol Chem, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD APR PY 1998 VL 15 IS 4 BP 513 EP 514 PG 2 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA ZL090 UT WOS:000073397800004 ER PT J AU Ibeanu, GC Blaisdell, J Ghanayem, BI Beyeler, C Benhamou, S Bouchardy, C Wilkinson, GR Dayer, P Daly, AK Goldstein, JA AF Ibeanu, GC Blaisdell, J Ghanayem, BI Beyeler, C Benhamou, S Bouchardy, C Wilkinson, GR Dayer, P Daly, AK Goldstein, JA TI An additional defective allele, CYP2C19*5, contributes to the S-mephenytoin poor metabolizer phenotype in Caucasians SO PHARMACOGENETICS LA English DT Article DE mephenytoin; CYP2C19; polymorphisms ID OXIDATION POLYMORPHISM; ESCHERICHIA-COLI; CHINESE SUBJECTS; HYDROXYLATION; EXPRESSION; CYP2C19; IDENTIFICATION; DEBRISOQUIN; POPULATION; SUBFAMILY AB The metabolism of the anticonvulsant drug mephenytoin exhibits a genetic polymorphism in humans. This polymorphism exhibits marked racial heterogeneity, with the poor metabolizer PM phenotype representing 13-23% of oriental populations, but only 2-5% of Caucasian populations. Two defective CYP2C19 alleles (CYP2C19*2 and CYP2C19*3) have been described, which account for more than 99% of Oriental poor metabolizer alleles but only approximately 87% of Caucasian poor metabolizer alleles. Therefore, additional defects presumably contribute to the poor metabolizer in Causasians. Recent studies have found a third mutation CYP2C19*4, which accounts for approximately 3% of Caucasian poor metabolizer alleles. A fourth rare mutation (CYP2C19*5A) (C-99,A(991),Ile(331);C1297T,Arg(433)-->Trp) resulting in an Arg(433) to Trp substitution in the heme-binding region has been reported in a single Chinese poor metaboliser outlier belonging to the Bai ethnic group. The present study identifies a second variant allele CYP2C19*5B (C-99-->T; A(991)-->G, Ile(331)-->Val; C-1297-->T, Arg(433)-->Trp in one of 37 Caucasian poor metabolizers. The frequency of the CYP2C19*5 alleles is low in Chinese (approximately 0.25% in the Bai ethnic group) and Caucasians (< 0.9%). However, these alleles contribute to the poor metabolizer phenotype in both ethnic groups and increases the sensitivity of the genetic tests for identifying defective alleles to approximately 100% in Chinese poor metabolizers and 92% in Caucasian poor metabolizers genotyped in our laboratory. The Arg(433) to Trp mutation in the heme-binding region essentially abolishes activity of recombinant CYP2C19*5A toward S-mephenytoin and tolbutamide, which is consistent with the conclusion that CYP2C19*5 represents poor metabolizer alleles. Pharmacogenetics 8: 129-135 (C) 1998 Lippincott-Raven Publishers. C1 Univ Bern, Inselspital, Rheumatol Klin, CH-3010 Bern, Switzerland. INSERM, U351, Villejuif, France. Geneva Canc Registry, Dept Pharmacol, Geneva, NY USA. Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. Univ Hosp Geneva, Dept Clin Pharmacol, Geneva, Switzerland. Univ Newcastle Upon Tyne, Dept Pharmacol Sci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. NIEHS, Res Triangle Pk, NC 27709 USA. RP Goldstein, JA (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM goldstein@niehs.nih.gov RI Daly, Ann/H-3144-2011; Benhamou, Simone/K-6554-2015 OI Daly, Ann/0000-0002-7321-0629; NR 41 TC 74 Z9 79 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD APR PY 1998 VL 8 IS 2 BP 129 EP 135 DI 10.1097/00008571-199804000-00006 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA ZW379 UT WOS:000074405100006 PM 10022751 ER PT J AU Hall, FS Wilkinson, LS Humby, T Inglis, W Kendall, DA Marsden, CA Robbins, TW AF Hall, FS Wilkinson, LS Humby, T Inglis, W Kendall, DA Marsden, CA Robbins, TW TI Isolation rearing in rats: Pre- and postsynaptic changes in striatal dopaminergic systems SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article; Proceedings Paper CT 3rd European Pharmacology, Biochemistry and Behavior Meeting CY JAN 04-11, 1998 CL MORZINE, FRANCE DE isolation rearing; dopamine; nucleus accumbens; in vivo microdialysis; cAMP ID SOCIAL-ISOLATION; PREPULSE INHIBITION; LATENT INHIBITION; NUCLEUS-ACCUMBENS; STARTLE RESPONSE; AMPHETAMINE; COCAINE; STEREOTYPY; RECEPTORS; DEFICITS AB Isolation rearing of rats produces a behavioral syndrome indicative of altered dopamine (DA) function in the nucleus accumbens (NAC). The present experiments extend these findings by investigating: (a) interactions between isolation rearing and repeated handling/testing on presynaptic DA function in the NAC using in vivo microdialysis; (b) the dose-response curve for the effects of d-amphetamine, and the responses elicited by high potassium, using in vivo microdialysis; and (c) postsynaptic function in isolates as indexed by DA receptor-linked cAMP production. Experiment 1 showed that both isolation rearing and repeated handling/testing had effects on monoamine function in the NAG. However. while both manipulations enhanced DA release evoked by d-amphetamine, only isolated rats had elevated basal DA levels. Opposite neurochemical changes were observed with respect to the serotonin metabolite 5-HIAA, isolates having lower, and repeatedly handled/tested animals having higher, extracellular levels. Experiment 2 provided evidence for enhanced d-amphetamine-evoked DA release in isolated animals, while potassium-evoked DA release was reduced. Experiment 3 provided evidence that the isolation rearing induced changes in presynaptic DA function were accompanied by postsynaptic changes. Specifically, the inhibitory influence of the D-2 receptor on D-1 receptor-stimulated cAMP production was attenuated in ventral striatal slices taken from isolates, suggesting a functional downregulation of D-2 receptors. (C) 1998 Elsevier Science Inc. C1 Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. Univ Nottingham, Queens Med Ctr, Sch Med, Dept Physiol & Pharmacol, Nottingham NG7 2UH, England. RP Hall, FS (reprint author), NIAAA, NIH, 10-0C207,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Humby, Trevor/A-1698-2010; Hall, Frank/C-3036-2013; OI Hall, Frank/0000-0002-0822-4063; HUMBY, trevor/0000-0002-1840-1799 FU NIDA NIH HHS [DA 05408]; Wellcome Trust NR 40 TC 166 Z9 170 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD APR PY 1998 VL 59 IS 4 BP 859 EP 872 DI 10.1016/S0091-3057(97)00510-8 PG 14 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA ZJ810 UT WOS:000073255800013 PM 9586842 ER PT J AU Martinez, LJ Sik, RH Chignell, CF AF Martinez, LJ Sik, RH Chignell, CF TI Fluoroquinolone antimicrobials: Singlet oxygen, superoxide and phototoxicity SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID INDUCED CUTANEOUS PHOTOTOXICITY; QUINOLONE ANTIBACTERIAL AGENTS; MICE; GENERATION; 8-POSITION; EPR; PH AB The fluoroquinolone antibacterial agents possess photosensitizing properties that lead to phototoxic responses in both human and animal subjects, The phototoxicity order reported in humans is: fleroxacin > lomefloxacin, pefloxacin >> ciprofloxacin > enoxacin, norfloxacin and ofloxacin, Studies both in vivo and in vitro have related this phototoxicity to the generation of reactive oxygen species including hydrogen peroxide and the hydroxyl radical. We determined the quantum yields of singlet oxygen generation (Phi(Delta)) by detection of the singlet oxygen (O-1(2)) luminescence at 1270 mn for several fluoroquinolones, naphthyridines and other structurally related compounds. All the fluoroquinolones examined have low Phi(Delta) values ranging from 0.06 to 0.09 in phosphate buffer at pD 7.5, We also determined the O-1(2) quenching constants for these compounds and their values were on the order of 10(6) M-1 s(-1), except for lomefloxacin whose rate constant was 1.8 x 10(7) M-1 s(-1). The Phi(Delta) values were significantly decreased in a solvent of lower polarity such as methanol (0.007 less than or equal to Phi(Delta) less than or equal to 0.02), The production of O-1(2) by these antibiotics did not correlate with the order reported for their phototoxicity, We also measured the photogeneration (lambda > 300 mm) of superoxide by these antibacterials in dimethylsulfoxide using electron paramagnetic resonance and the spin trap 5,5-dimethyl-1-pyrroline N-oxide. Although there is not a one-to-one correspondence between the relative rates of superoxide generation and the phototoxicity ranking of the fluoroquinolones, the more phototoxic compounds tended to produce superoxide at a faster rate. Nevertheless, the magnitudes of the observed differences do not appear sufficient to explain the range of fluoroquinolone phototoxicity potencies in human and animal subjects in general and the high activity of fleroxacin and lomefloxacin in particular. For these latter drugs the photoinduced loss of the F-8 atom as fluoride and the concomitant generation of a highly reactive carbene at C-8 provide a more plausible mechanism for their potent phototoxic and photocarcinogenic properties. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Chignell, CF (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM chignell@niehs.nih.gov NR 23 TC 130 Z9 137 U1 4 U2 28 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD APR PY 1998 VL 67 IS 4 BP 399 EP 403 DI 10.1111/j.1751-1097.1998.tb05217.x PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZG965 UT WOS:000073057800009 PM 9559584 ER PT J AU Smith, MF Jaszczak, RJ AF Smith, MF Jaszczak, RJ TI An analytic model of pinhole aperture penetration for 3D pinhole SPECT image reconstruction SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 4th International Meeting on Fully Three-Dimensional Image Reconstruction in Radiology and Nuclear Medicine CY JUN 25-28, 1997 CL NEMACOLIN WOODLANDS CONF CTR, LAUREL HIGHLANDS, PENNSYLVANIA HO NEMACOLIN WOODLANDS CONF CTR ID EMISSION COMPUTED-TOMOGRAPHY; ULTRA-HIGH-RESOLUTION; COLLIMATOR; HEAD AB Photons penetrate the attenuating material close to the aperture of pinhole collimators in nuclear medicine, broadening the tails of point spread functions (PSFs) and degrading the resolution of planar and SPECT images. An analytic approximation has been developed that models this penetration contribution to the PSF for knife-edge point pinhole apertures. The approximation has the form exp(-gamma r), where r is the distance on the detector surface from the projection of the point source through the pinhole. The rolloff coefficient gamma is a function of the photon energy, point source location and the design parameters of the collimator. There was excellent agreement between measured values of gamma from photon transport simulations of I-131 point sources (364 keV emission only) and theoretical predictions from the analytic formula. Predicted gamma values from the analytic formula averaged 25% greater than measured values from experimental I-131 point source acquisitions. Photon transport simulations were performed that modelled the 364 keV and less abundant 637 and 723 keV emissions and scatter within the scintillation crystal. Measured gamma values from these simulations averaged 12% greater than the experimental values, indicating that about half of the error between the analytic formula and the experimental measurements was due to unmodelled 637 and 723 keV emissions. The remaining error may be due in part to scatter in the pinhole region and backscatter from gamma camera components behind the scintillation crystal. The analytic penetration model was used in designing Metz filters to compensate for penetration blur and these filters were applied to the projection data as part of 3D SPECT image reconstruction. Image resolution and contrast were improved in simulated and experimental I-131 tumour phantom studies. This analytic model of pinhole aperture penetration can be readily incorporated into iterative 3D SPECT pinhole reconstruction algorithms. C1 Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. Duke Univ, Dept Biomed Engn, Durham, NC 27706 USA. RP Smith, MF (reprint author), NIH, MSC 1180,10 Ctr Dr,Bldg 10,Room 1C401, Bethesda, MD 20892 USA. FU NCI NIH HHS [R01-CA33541] NR 27 TC 41 Z9 42 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD APR PY 1998 VL 43 IS 4 BP 761 EP 775 DI 10.1088/0031-9155/43/4/006 PG 15 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA ZH069 UT WOS:000073069000006 PM 9572502 ER PT J AU Daube-Witherspoon, ME Carson, RE AF Daube-Witherspoon, ME Carson, RE TI Axial slice width in 3D PET: characterization and potential improvement with axial interleaving SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 4th International Meeting on Fully Three-Dimensional Image Reconstruction in Radiology and Nuclear Medicine CY JUN 25-28, 1997 CL NEMACOLIN WOODLANDS CONF CTR, LAUREL HIGHLANDS, PENNSYLVANIA HO NEMACOLIN WOODLANDS CONF CTR ID IMAGE-RECONSTRUCTION; PERFORMANCE; SCANNER AB The axial slice width for the GE Advance PET scanner has previously been reported to be worse for 3D acquisitions than for 2D. The goals of this study were to investigate the source(s) of this observed difference and to assess whether the 3D axial slice width could be significantly improved by acquisition and simultaneous reconstruction of axially interleaved data. The axial slice width was measured for the three acquisition modes of the Advance scanner ('standard' high-sensitivity 2D, high-resolution 2D and 3D), with the septa both extended and retracted. A significant degradation in the axial slice width for 3D compared with that for high-sensitivity 2D mode was seen. Near the centre, this difference can largely be attributed to septa collimation effects of the 2D data. At larger radial positions, axial mispositioning of cross-coincidences in 2D acquisitions overshadows the effects of septa collimation, while 3D reconstruction effects also become more important. The axial slice width was estimated to improve by 0.3-1.1 mm with interleaving. This modest improvement would be accompanied by an increase in image noise, since an axial filter with a higher cut-off would be required in the 3D reconstruction to achieve this resolution in the image. C1 NIH, Warren G Magnuson Clin Ctr, Positron Emiss Tomog Dept, Bethesda, MD 20892 USA. RP Daube-Witherspoon, ME (reprint author), NIH, Warren G Magnuson Clin Ctr, Positron Emiss Tomog Dept, Bldg 10-1C497,10 Ctr Dr,MSC 1180, Bethesda, MD 20892 USA. EM daube-witherspoon@nih.gov RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 10 TC 4 Z9 4 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD APR PY 1998 VL 43 IS 4 BP 921 EP 928 DI 10.1088/0031-9155/43/4/019 PG 8 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA ZH069 UT WOS:000073069000019 PM 9572515 ER PT J AU Kamara, K Eskay, R Castonguay, T AF Kamara, K Eskay, R Castonguay, T TI High-fat diets and stress responsivity SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE fat; diet; stress; corticosterone; obesity; adiposity; insulin resistance ID RATS; WEIGHT AB Adult male rats were fed one of five diets varying in fat composition (Purina Chow or soy bran oil, corn oil, menhaden oil, or olive oil added to chow) for 10 weeks. After 3 days of access, no differences between groups were found in plasma corticosterone measured at light onset and light offset. During Week 2, restraint stress tests were performed. High-far diets promoted significantly higher stimulated corticosterone levels. During Week 6 all rats were given an oral glucose tolerance test. Rats fed the corn and soybean oil diets had significantly elevated blood glucose 2 h after glucose intubation. Euglycemia was restored after 3 hours in all but the soybean oil group. During Week 9, a second stress test was performed. No differences in initial stress responsivity was observed, but groups fed the menhaden, soybean and olive oil diets had significantly higher corticosterone 1 h after the end of restraint. The corn oil, olive oil and soybean oil diets promoted transient hyperphagia. By the end of the experiment, the group fed the menhaden oil diet weighed significantly less and ate less than the remaining groups. These data demonstrate that stress responsivity is briefly enhanced during initial access to the high-fat regimens. Continued high-fat feeding results in an impaired ability to restore basal corticosterone following stress. (C) 1998 Elsevier Science Inc. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. NIAAA, Neuroendocrinol Neurochem Sect, Clin Studies Lab, NIH, Bethesda, MD 20892 USA. RP Castonguay, T (reprint author), Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. OI Castonguay, Thomas/0000-0003-1176-5095 NR 13 TC 58 Z9 58 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD APR PY 1998 VL 64 IS 1 BP 1 EP 6 DI 10.1016/S0031-9384(97)00534-9 PG 6 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA ZW317 UT WOS:000074398100001 PM 9661975 ER PT J AU Markowska, AL Spangler, EL Ingram, DK AF Markowska, AL Spangler, EL Ingram, DK TI Behavioral assessment of the senescence-accelerated mouse (SAM P8 and R1) SO PHYSIOLOGY & BEHAVIOR LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-Neuroscience CY OCT 25-30, 1997 CL NEW ORLEANS, LA SP Soc Neurosci DE senescence-accelerated mouse (SAM); working memory; reference memory; water maze; sensor motor skills; exploratory activity; emotionality ID AGE-RELATED-CHANGES; SPATIAL MEMORY; MURINE MODEL; WATER MAZE; SAM-P/8; STRAIN; MICE; ACQUISITION; ANXIETY; BRAIN AB Senescence-accelerated mice (SAM P8 and R1) were behaviorally assessed in a cross-sectional study at 4 and 15 months of age. Behavioral measures included memory (place discrimination and repeated acquisition in a water maze), sensorimotor performance (turning in an alley, traversing bridges, wire rod hanging, and falls from a wire screen), psychomotor performance (open-field exploration), and emotionality (entries in a plus maze, grooming, and defecation in a plus maze and in an open field). In the water maze, aged P8 mice were impaired in place discrimination end in repeated acquisition tasks, demonstrating evidence of an age-related decline in spatial memory processing abilities. The demonstration of this impairment, however, was complicated by noncognitive factors, such as the tendency of many older P8 mice to float. Sensorimotor skill impairment was accelerated with age in P8 mice, but not in R1 mice, and this impairment vas present despite the lack of age-related changes in body weight in P8 mice. Although PS and R1 mice were not different in general activity at old age, P8 mice were substantially more hyperactive in an open field and in the plus maze than Ri mice when compared at young age. Independent of age, P8 mice demonstrated a reduction of anxiety-like behavior in the plus maze. Taken as a whole, the data suggest that although age-related behavioral alterations occur in the P8 mice, some of these changes are evident at 4 months of age. Thus, the behavioral abnormalities that exist not only represent an accelerated aging phenomenon but may also be considered a developmental pathology. (C) 1998 Elsevier Science Inc. C1 Johns Hopkins Univ, Dept Psychol, Neuromnemon Lab, Baltimore, MD 21218 USA. NIA, Mol Physiol & Genet Sect, Nathan W Shock Labs, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. RP Markowska, AL (reprint author), Johns Hopkins Univ, Dept Psychol, Neuromnemon Lab, 3400 W Charles St, Baltimore, MD 21218 USA. EM Alicja@jhunix.hcf.jhu.edu FU NIA NIH HHS [AG07735] NR 43 TC 56 Z9 63 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD APR PY 1998 VL 64 IS 1 BP 15 EP 26 DI 10.1016/S0031-9384(98)00011-0 PG 12 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA ZW317 UT WOS:000074398100003 PM 9661977 ER PT J AU Piatigorsky, J AF Piatigorsky, J TI Gene sharing in lens and cornea: Facts and implications SO PROGRESS IN RETINAL AND EYE RESEARCH LA English DT Review ID ALPHA-B-CRYSTALLIN; HEAT-SHOCK PROTEIN; CLASS-3 ALDEHYDE DEHYDROGENASE; GLUTATHIONE-S-TRANSFERASE; GROWTH FACTOR-II; CHICKEN DELTA-1-CRYSTALLIN GENE; DEPENDENT ALCOHOL-DEHYDROGENASE; NEURONAL SURVIVAL FACTOR; MAJOR SOLUBLE-PROTEIN; MAMMALIAN EYE LENS AB The major water-soluble proteins (crystallins) responsible for the optical properties of the cellular lenses of vertebrates and invertebrates are surprisingly diverse and often differ among species (i.e., are taxon-specific), Many crystallins are encoded by the identical gene specifying a stress protein or a metabolic enzyme which has non-refractive functions in numerous tissues. This double use of a distinct protein has been called gene sharing. Abundant expression of various metabolic enzymes also occurs in a taxon-specific manner in corneal epithelial cells, suggesting that gene sharing extends to this transparent tissue. It has been proposed that one of the most abundant corneal enzymes (aldehyde dehydrogenase class 3) may protect the eye by directly absorbing ultraviolet light, as well as by providing an enzymatic function. It also seems possible that the high expression of corneal enzymes (5-40% of the water-soluble proteins) may reduce scattering in the corneal epithelium by minimizing spatial fluctuations in refractive index as they do in the lens. Thus, gene sharing may be a widespread phenomenon encompassing the lens, cornea and probably other systems. Lens-preferred expression of crystallin genes is integrated in a complex developmental program utilizing in many cases Pax-6. The differential expression of alpha B-crystallin (a small heat shock protein) in different tissues involves the combinatorial use of both shared and lens-specific cis-control elements. Corneal-preferred gene expression appears to depend in part on induction by environmental influences. Among the implications of gene sharing are that gene duplication is not required for the evolution of a new protein phenotype, a change in gene regulation is sufficient, that proteins may be under more than one selective constraint, affecting their evolutionary clock, and that it would be prudent to consider the possibility that any given gene may have important unrecognized roles when planning to implement gene therapy in the future. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NR 287 TC 106 Z9 108 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1350-9462 J9 PROG RETIN EYE RES JI Prog. Retin. Eye Res. PD APR PY 1998 VL 17 IS 2 BP 145 EP 174 DI 10.1016/S1350-9462(97)00004-9 PG 30 WC Ophthalmology SC Ophthalmology GA 108CY UT WOS:000075249500001 PM 9695791 ER PT J AU Hsi, LC Eling, TE AF Hsi, LC Eling, TE TI Inhibition of EGF-dependent mitogenesis by prostaglandin E-2 in Syrian hamster embryo fibroblasts SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID EPIDERMAL GROWTH-FACTOR; ACTIVATED PROTEIN-KINASE; HUMAN-BREAST-CANCER; ARACHIDONIC-ACID METABOLISM; TUMOR-SUPPRESSOR GENE; SMOOTH-MUSCLE CELLS; MAP KINASE; SIGNAL-TRANSDUCTION; ASPIRIN USE; CLINICAL IMPLICATIONS AB Lipid metabolism can play an important role in the development and progression of human cancers. We have used Syrian hamster embryo (SHE) fibroblasts as a model system to study how lipid metabolites can alter cell proliferation and apoptosis. For example, the linoleic acid metabolite 13(S)-HpODE enhances EGF-dependent growth by inhibiting de-phosphorylation of the EGFR which leads to activation of the MAP kinase pathway. In contrast, the arachidonic acid metabolite, PGE(2), inhibits EGF-dependent mitogenesis and the expression of the proto-oncogenes c-myc, c-jun, and jun-B. In this study, we have investigated the mechanism by which PGE(2) attenuates these responses by studying the EGF signaling cascade in SHE cells. PGE(2) pretreatment caused a concentration-dependent decrease in EGF-dependent phosphorylation of MAP kinase and a corresponding inhibition of EGF-stimulated MAP kinase activity. Pretreatment of the SHE cells with PGE(2) had little effect on the magnitude of EGF-dependent receptor auto-phosphorylation and the phosphorylation of GAP suggesting a down-stream target. Treatment of cells with forskolin and EGF causes similar inhibition of MAP kinase phosphorylation as observed with PGE(2) and EGF. Since PGE(2) elevates cAMP in these cells, it may act by altering cAMP accumulation. Raf-1 activity can be inhibited by a cAMP-dependent process. Raf-1 activity, measured by phosphorylation of Mek-1, was attenuated by the addition of PGE(2). To determine if inhibition of Raf-1 activity causes inhibition of the MAP kinase pathway, cells were concomitantly incubated with PGE(2) and EGF. Inhibition of MAP kinase phosphorylation was observed. From these data, we propose that in SHE cells PGE(2) increases cAMP levels, which in turn causes inhibition of Raf-1 activity. The MAP kinase pathway is thus downregulated which decreases mitogenesis and proto-oncogene expression. This study demonstrates that an arachidonic acid metabolite can modulate phosphorylation and activity of key signal transduction proteins in a growth factor mitogenic pathway. C1 NIEHS, Mol Carcinogenesis Lab, Eicosanoid Biochem Sect, Res Triangle Pk, NC 27709 USA. RP Eling, TE (reprint author), NIEHS, Mol Carcinogenesis Lab, Eicosanoid Biochem Sect, POB 12233, Res Triangle Pk, NC 27709 USA. NR 51 TC 9 Z9 9 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD APR PY 1998 VL 58 IS 4 BP 271 EP 281 DI 10.1016/S0952-3278(98)90036-9 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA ZU301 UT WOS:000074183000004 PM 9654400 ER PT J AU Rosen, M Lin, SL Wolfson, H Nussinov, R AF Rosen, M Lin, SL Wolfson, H Nussinov, R TI Molecular shape comparisons in searches for active sites and functional similarity SO PROTEIN ENGINEERING LA English DT Article ID PROTEIN-PROTEIN RECOGNITION; ALLOSTERIC CHORISMATE MUTASE; COMPUTER VISION; SURFACE COMPLEMENTARITY; BIOMOLECULAR DOCKING; AUTOMATED DOCKING; BINDING-ENERGY; ALGORITHM; COMPLEXES; FLEXIBILITY AB Here we examine the reliability of surface comparisons in searches for active sites in proteins. Detection of a patch of surface on one protein which is similar to an active site in another, may suggest similarities in enzymatic mechanisms, in enzyme functions and implicate a potential target for ligand/inhibitor design. Specifically, we compare the efficacy of molecular surface comparisons with comparisons of surface atoms and of C-alpha backbone atoms. We further investigate comparisons of specific atoms, belonging to a predefined pattern of catalytic residues versus comparisons of molecular- surfaces and, separately, of surface atoms, This aspect is particularly relevant, as catalytic residues may be (partially) buried. We also explore active site comparisons versus comparisons in which the entire molecular surfaces are scanned, While here we focus on the geometrical aspect of the problem, we also investigate the effect of adding residue labels in these comparisons. Our extensive studies cover the serine proteases, containing the highly conserved triad motif, and the chorismate mutases, Since such active site comparisons entail comparisons between unconnected points in 3D space, an order-independent comparison technique is necessary. The geometric hashing algorithm is ideally suited to handling such a task. It can perform both global shape matching for the whole surfaces of large protein molecules and searching for local shape similarities for small surface moths, Our results show that molecular surface comparisons work best when the similarity is high. As the similarity deteriorates, the number of potential solutions increases rapidly, making their ranking difficult, particularly when scanning entire molecular surfaces, Utilizing atomic coordinates directly appears more adequate under such circumstances. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, SAIC, Frederick, MD 21702 USA. Tel Aviv Univ, Sch Math Sci, Dept Comp Sci, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Fac Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, SAIC, Bldg 469,Room 151, Frederick, MD 21702 USA. RI Wolfson, Haim/A-1837-2011 FU NCI NIH HHS [N0.1-CO-74102] NR 61 TC 68 Z9 69 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 APR PY 1998 VL 11 IS 4 BP 263 EP 277 DI 10.1093/protein/11.4.263 PG 15 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA ZV496 UT WOS:000074310400003 PM 9680188 ER PT J AU Miroshnikov, KA Marusich, EI Cerritelli, ME Cheng, NQ Hyde, CC Steven, AC Mesyanzhinov, VV AF Miroshnikov, KA Marusich, EI Cerritelli, ME Cheng, NQ Hyde, CC Steven, AC Mesyanzhinov, VV TI Engineering trimeric fibrous proteins based on bacteriophage T4 adhesins SO PROTEIN ENGINEERING LA English DT Article DE adhesin; bacteriophage tail-fiber; coiled coil; fibritin; protein folding ID COILED-COIL STRUCTURE; TAIL-FIBER AB The adsorption specificity of bacteriophage T4 is determined by genes 12 and 37, encoding the short tail-fibers (STF) and the distal part of the long tail-fibers (LTF), respectively Both are trimeric proteins with rod domains made up of similar tandem quasi-repeats, similar to 40 amino acids long. Their assembly requires the viral chaperones gp57A and gp38, Here we report that fusing fragments of gp12 and gp37 to another trimeric T4 fibrous protein, fibritin, facilitates correct assembly, thereby by-passing the chaperone requirement. Fibritin is an alpha-helical coiled coil protein whose C-terminal part (fibritin E, comprising the last 120 residues) has recently been solved to atomic resolution, Gp12 fragments of 109 and 70 amino acids, corresponding to three and two quasi-repeats respectively, were fused to the C-terminus of fibritin E. A similar chimera was designed for the last 63 residues of gp37, which contain four copies of the pentapeptide Gly-X-His-X-His and assume a narrow rigid structure in the LTF distal tip, Expressed from plasmids, ail three chimeras form soluble trimers that are resistant to dissociation by SDS and digestion by trypsin, indicative of correct folding and oligomerization. C1 NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. Bach Inst Biochem, Howard Hughes Med Inst, Moscow 117081, Russia. RP Steven, AC (reprint author), NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. NR 20 TC 27 Z9 28 U1 2 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD APR PY 1998 VL 11 IS 4 BP 329 EP 332 DI 10.1093/protein/11.4.329 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA ZV496 UT WOS:000074310400010 PM 9680195 ER PT J AU Yan, XJ Day, P Hollis, T Monzingo, AF Schelp, E Robertus, JD Milne, GWA Wang, SM AF Yan, XJ Day, P Hollis, T Monzingo, AF Schelp, E Robertus, JD Milne, GWA Wang, SM TI Recognition and interaction of small rings with the ricin A-chain binding site SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE ricin structure; inhibitor design; energy minimization ID ACTIVE-SITE; FREE-ENERGIES; MUTAGENESIS; SIMULATION; SOLVATION AB Ricin A-chain is an N-glucosidase that attacks ribosomal RNA at a highly conserved adenine residue, Our recent crystallographic studies show that not only adenine and formycin, but also pterin based rings can bind in the active site of ricin, For a better understanding of the means by which ricin recognizes adenine rings, the geometries and interaction energies were calculated for a number of complexes between ricin and tautomeric modifications of formycin, adenine, pterin, and guanine, These were studied by molecular mechanics, semi-empirical quantum mechanics, and ab initio quantum mechanical methods, The calculations indicate that the formycin ring binds better than adenine and pterin better than formycin, a result that is consistent with the crystallographic data, A tautomer of pterin that is not in the low energy form in either the gas phase or in aqueous solution has the best interaction with the enzyme, The net interaction energy, defined as the interaction energy calculated in vacuo between the receptor and an inhibitor minus the solvation energy of the inhibitor, provides a good prediction of the ability of the inhibitor to bind to the receptor, The results from experimental and molecular modeling work suggest that the ricin binding site is not flexible and may only recognize a limited range of adenine-like rings. (C) 1998 Wiley-Liss, Inc. C1 Georgetown Univ, Med Ctr, Drug Discovery Program, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, GICCS, Washington, DC 20007 USA. Univ Texas, Dept Chem & Biochem, Austin, TX 78712 USA. NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Wang, SM (reprint author), Georgetown Univ, Med Ctr, Drug Discovery Program, 3970 Reservoir Rd, Washington, DC 20007 USA. FU NIGMS NIH HHS [GM 30048] NR 21 TC 30 Z9 31 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-3585 J9 PROTEINS JI Proteins PD APR 1 PY 1998 VL 31 IS 1 BP 33 EP 41 DI 10.1002/(SICI)1097-0134(19980401)31:1<33::AID-PROT4>3.0.CO;2-I PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZE824 UT WOS:000072835300004 PM 9552157 ER PT J AU Rosen, JB Schulkin, J AF Rosen, JB Schulkin, J TI From normal fear to pathological anxiety SO PSYCHOLOGICAL REVIEW LA English DT Review ID CORTICOTROPIN-RELEASING FACTOR; POSTTRAUMATIC-STRESS-DISORDER; FOS MESSENGER-RNA; POTENTIATED STARTLE PARADIGM; AMYGDALA-KINDLED SEIZURES; OBSESSIVE-COMPULSIVE DISORDER; MIDBRAIN PERIAQUEDUCTAL GRAY; VISUAL CONDITIONED-STIMULI; CENTRAL NUCLEUS LESIONS; LONG-TERM POTENTIATION AB In this article the authors address how pathological anxiety may develop from adaptive fear states. Fear responses (e.g., freezing, startle, heart rate and blood pressure changes, and increased vigilance) are functionally adaptive behavioral and perceptual responses elicited during danger to facilitate appropriate defensive responses that can reduce danger or injury (e.g., escape and avoidance). Fear is a central motive state of action tendencies subserved by fear circuits, with the amygdala playing a central role. Pathological anxiety is conceptualized as an exaggerated fear state in which hyperexcitability of fear circuits that include the amygdala and extended amygdala (i.e., bed nucleus of the stria terminalis) is expressed as hypervigilance and increased behavioral responsivity to fearful stimuli. Reduced thresholds for activation and hyperexcitability in fear circuits develop through sensitization-or kindling-like processes that involve neuropeptides, hormones, and other proteins. Hyperexcitability in fear circuits is expressed as pathological anxiety that is manifested in the various anxiety disorders. C1 Univ Delaware, Dept Psychol, Newark, DE 19716 USA. NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. RP Rosen, JB (reprint author), Univ Delaware, Dept Psychol, 220 Wolf Hall, Newark, DE 19716 USA. EM jrosen@udel.edu NR 328 TC 406 Z9 410 U1 13 U2 62 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0033-295X EI 1939-1471 J9 PSYCHOL REV JI Psychol. Rev. PD APR PY 1998 VL 105 IS 2 BP 325 EP 350 DI 10.1037/0033-295X.105.2.325 PG 26 WC Psychology; Psychology, Multidisciplinary SC Psychology GA ZJ323 UT WOS:000073202500006 PM 9577241 ER PT J AU Schulkin, J Gold, PW McEwen, BS AF Schulkin, J Gold, PW McEwen, BS TI Induction of corticotropin-releasing hormone gene expression by glucocorticoids: Implication for understanding the states of fear and anxiety and allostatic load SO PSYCHONEUROENDOCRINOLOGY LA English DT Review DE corticotropin-releasing hormone; glucocorticoids; fear/anxiety; amygdala; bed nucleus of the stria terminalis; hippocampus; allostatic load ID POSTTRAUMATIC-STRESS-DISORDER; FACTOR-LIKE IMMUNOREACTIVITY; URINARY-FREE CORTISOL; MESSENGER-RNA; RAT-BRAIN; PARAVENTRICULAR NUCLEUS; POTENTIATED STARTLE; FACTOR-RECEPTOR; BEHAVIORAL-INHIBITION; MAJOR DEPRESSION AB Evidence supports the idea of two distinct corticotropin-releasing hormone (CRH) systems in the brain: one which is constrained by glucocorticoids and the other which is not. It is this latter system that includes two primary sites (central nucleus of the amygdala and the lateral bed nucleus of the stria terminalis) in which the regulation of CRH gene expression can be disassociated from that of the paraventricular nucleus of the hypothalamus. It is this other system that we think is linked to fear and anxiety and to clinical syndromes (excessively shy fearful children, melancholic depression, post-traumatic stress disorder and self-administration of psychotropic drugs). The excess glucocorticoids and CRH, and the state of anticipatory anxiety, contribute to allostatic load, a new term that refers to the wear and tear on the body and brain arising from attempts to adapt to adversity. (C) 1998 Published by Elsevier Science Ltd. All rights reserved. C1 NIMH, Clin Neuroendocrinol Branch, Behav Neurosci Unit, Bethesda, MD 20892 USA. Georgetown Univ, Dept Physiol & Biophys, Washington, DC USA. Rockefeller Univ, Dept Neuroendocrinol, New York, NY 10021 USA. RP Schulkin, J (reprint author), NIMH, Clin Neuroendocrinol Branch, Behav Neurosci Unit, Bldg 10, Bethesda, MD 20892 USA. EM jay@codon.nih.gov NR 139 TC 278 Z9 282 U1 2 U2 19 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD APR PY 1998 VL 23 IS 3 BP 219 EP 243 DI 10.1016/S0306-4530(97)00099-1 PG 25 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 100KA UT WOS:000074814300002 PM 9695128 ER PT J AU Mecklenburg, RE AF Mecklenburg, RE TI Tobacco: Addiction, oral health, and cessation SO QUINTESSENCE INTERNATIONAL LA English DT Article C1 Natl Canc Inst, Smoking & Tobacco Control Program, Bethesda, MD 20892 USA. Agcy Hlth Care Policy & Res, Rockville, MD USA. RP Mecklenburg, RE (reprint author), 12304 Rivers Edge Dr, Potomac, MD 20854 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU QUINTESSENCE PUBL CO INC PI CAROL STREAM PA 551 NORTH KIMBERLY DR, CAROL STREAM, IL 60188-1881 USA SN 0033-6572 J9 QUINTESSENCE INT JI Quintessence Int. PD APR PY 1998 VL 29 IS 4 BP 250 EP 252 PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA ZK702 UT WOS:000073352600013 PM 9643264 ER PT J AU Choyke, PL Hricak, H Kenney, PJ Sandler, CM Bush, WH Clark, RL AF Choyke, PL Hricak, H Kenney, PJ Sandler, CM Bush, WH Clark, RL TI The future of research in genitourinary radiology: Through the looking glass - A view from the Society of Uroradiology SO RADIOLOGY LA English DT Editorial Material DE genitourinary system; radiology and radiologists; research; subspecialty society messages ID MR; FEASIBILITY; DIAGNOSIS; EFFICACY C1 NIH, Dept Radiol, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Alabama, Dept Radiol, Birmingham, AL USA. Univ Texas, Sch Med, Dept Radiol, Houston, TX USA. Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA. Univ N Carolina, Sch Med, Dept Radiol, Chapel Hill, NC 27514 USA. RP Choyke, PL (reprint author), NIH, Dept Radiol, Warren G Magnuson Clin Ctr, 10 Ctr Dr,Bldg 10,Rm 1C660, Bethesda, MD 20892 USA. NR 11 TC 8 Z9 8 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 1998 VL 207 IS 1 BP 3 EP 6 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZD211 UT WOS:000072662500002 PM 9530290 ER PT J AU Murugesan, R Afeworki, M Cook, JA Devasahayam, N Tschudin, R Mitchell, JB Subramanian, S Krishna, MC AF Murugesan, R Afeworki, M Cook, JA Devasahayam, N Tschudin, R Mitchell, JB Subramanian, S Krishna, MC TI A broadband pulsed radio frequency electron paramagnetic resonance spectrometer for biological applications SO REVIEW OF SCIENTIFIC INSTRUMENTS LA English DT Article ID FOURIER-TRANSFORM; EPR SPECTROMETER; SPECTROSCOPY; PENETRATION; ABSORPTION; RADICALS; TISSUE; OXYGEN; HEART AB A time-domain radio frequency (rf) electron paramagnetic resonance (EPR) spectrometer/imager (EPRI) capable of detecting and imaging free radicals in biological objects is described, The magnetic field was 10 mT which corresponds to a resonance frequency of 300 MHz for paramagnetic species. Short pulses of 20-70 ns from the signal generator, with rise times of less than 4 ns, were generated using high speed gates, which after amplification to 283 Vpp, were deposited into a resonator containing the object of interest. Cylindrical resonators containing parallel loops at uniform spacing were used for imaging experiments. The resonators were maintained at the resonant frequency by tuning and matching capacitors. A parallel resistor and overcoupled circuit was used to achieve Q values in the range 20-30. The transmit and receive arms were isolated using a transmit/receive diplexer. The dead time following the trailing edge of the pulse was about 450 ns. The first stage of the receive arm contained a low noise, high gain and fast recovery amplifier, suitable for detection of spin probes with spin-spin relaxation times (T-2) in the order of mu s. Detection of the induction signal was carried out by mixing the signals in the receiver arm centered around 300 MHz with a local oscillator at a frequency of 350 MHz. The amplified signals were digitized and summed using a 1 GHz digitizer/summer to recover the signals and enhance the signal-to-noise ratio (SNR). The time-domain signals were transformed into frequency-domain spectra, using Fourier transformation (FT). With the resonators used, objects of size up to 5 cm(3) could be studied in imaging experiments. Spatial encoding of the spins was accomplished by volume excitation of the sample in the presence of static field gradients in the range of 1.0-1.5 G/cm. The spin densities were produced in the form of plane integrals and images were reconstructed using standard back-projection methods. The image resolution of the phantom objects containing the spin probe surrounded by lossy biologic medium was better than 0.2 mm with the gradients used. To examine larger objects at local sites, surface coils were used to detect and image spin probes successfully. The results from this study indicate the potential of rf FT EPR for in vivo applications. In particular, rf FT EPR may provide a means to obtain physiologic information such as tissue oxygenation and redox status. (C) 1998 American Institute of Physics. C1 NCI, Div Clin Sci, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RP Krishna, MC (reprint author), NCI, Div Clin Sci, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. EM murali@helix.nih.gov NR 34 TC 43 Z9 43 U1 0 U2 7 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0034-6748 J9 REV SCI INSTRUM JI Rev. Sci. Instrum. PD APR PY 1998 VL 69 IS 4 BP 1869 EP 1876 DI 10.1063/1.1148857 PG 8 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA ZJ144 UT WOS:000073183900052 ER PT J AU Liu, JM AF Liu, JM TI Gene transfer for the eventual treatment of Fanconi's anemia SO SEMINARS IN HEMATOLOGY LA English DT Article ID UMBILICAL-CORD BLOOD; NECROSIS-FACTOR-ALPHA; GROUP-C GENE; BONE-MARROW TRANSPLANTATION; HUMAN HEMATOPOIETIC-CELLS; LONG-TERM HEMATOPOIESIS; COMPLEMENTATION GROUP-A; DNA-CROSS-LINKING; PERIPHERAL-BLOOD; INTERFERON-GAMMA C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Liu, JM (reprint author), NHLBI, Hematol Branch, NIH, 10-ACRF-7C103, Bethesda, MD 20892 USA. NR 95 TC 13 Z9 13 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD APR PY 1998 VL 35 IS 2 BP 168 EP 179 PG 12 WC Hematology SC Hematology GA ZG222 UT WOS:000072979400008 PM 9565158 ER PT J AU Adde, M Shad, A Venzon, D Arndt, C Gootenberg, J Neely, J Nieder, M Owen, W Seibel, N Wilson, W Horak, ID Magrath, I AF Adde, M Shad, A Venzon, D Arndt, C Gootenberg, J Neely, J Nieder, M Owen, W Seibel, N Wilson, W Horak, ID Magrath, I TI Additional chemotherapy agents improve treatment outcome for children and adults with advanced B-cell lymphomas SO SEMINARS IN ONCOLOGY LA English DT Review ID SMALL-NONCLEAVED-CELL; ACUTE LYMPHOBLASTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMAS; PEDIATRIC-ONCOLOGY; BURKITTS LYMPHOMAS; STAGE; IFOSFAMIDE; CYTARABINE; CHILDHOOD; ETOPOSIDE C1 NCI, Pediat Branch, Div Clin Sci, Bethesda, MD 20892 USA. Georgetown Univ, Sch Med, Div Pediat Hematol Oncol, Washington, DC USA. Mayo Clin, Dept Pediat Adolescent Med, Rochester, MN USA. Penn State Univ, Childrens Hosp, Div Hematol Oncol, Hershey, PA USA. Rainbow Babies & Childrens Hosp, Div Hematol & Oncol, Cleveland, OH 44106 USA. Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA. Childrens Hosp Kings Daughters, Norfolk, VA USA. RP Magrath, I (reprint author), NCI, Pediat Branch, Div Clin Sci, Bldg 10,Room 13N240, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 20 TC 38 Z9 39 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 1998 VL 25 IS 2 SU 4 BP 33 EP 39 PG 7 WC Oncology SC Oncology GA ZK911 UT WOS:000073376800006 PM 9578060 ER PT J AU de Vries, G Miura, RM AF de Vries, G Miura, RM TI Analysis of a class of models of bursting electrical activity in pancreatic beta-cells SO SIAM JOURNAL ON APPLIED MATHEMATICS LA English DT Article DE bursting electrical activity; pancreatic beta-cells; nonlinear oscillations; perturbed Hamiltonian systems; Mel'nikov's method; plateau fraction ID OSCILLATIONS; BIFURCATION; ISLETS; TRANSITION; CHANNEL; SYSTEM; JUMP AB Many models of bursting electrical activity (BEA) in pancreatic beta-cells have been proposed. BEA is characterized by a periodic oscillation of the membrane potential consisting of a silent phase during which the membrane potential is varying slowly and an active phase during which the membrane potential is undergoing rapid oscillations. An important experimental observation of BEA is a correlation between the rate of insulin release from beta-cells and the plateau fraction as a function of glucose concentration. The plateau fraction is the ratio of the duration of the active phase to the period of BEA. In [SIAM J. Appl. Math., 52 (1992), pp. 1627-1650], Pernarowski, Miura, and Kevorkian develop analytical techniques to determine the leading-order plateau fraction for one of the models, namely, the Sherman-Rinzel-Keizer (SRK) model [Biophys. J., 54 (1988), pp. 411-425]. Applicability of these techniques depends critically on the fact that the fast subsystem of the SRK model is an integrable system to leading order. In this paper, we extend the techniques of Pernarowski, Miura, and Kevorkian to a class of models of BEA, namely, those first-generation models consisting of three first-order ordinary differential equations. We show that the fast subsystem of these models can be reformulated as an integrable system to leading order. The relative ease with which this reformulation can be done depends on a biological property of the models, namely, the value of the integer exponent of the activation variable in the description of the voltage-gated K+ current. C1 Univ British Columbia, Dept Math, Vancouver, BC V6T 1Z2, Canada. Univ British Columbia, Inst Appl Math, Vancouver, BC V6T 1Z2, Canada. NIH, Math Res Branch, Bethesda, MD 20892 USA. Univ British Columbia, Dept Pharmacol & Therapeut, Vancouver, BC V6T 1Z3, Canada. RP de Vries, G (reprint author), Univ British Columbia, Dept Math, Vancouver, BC V6T 1Z2, Canada. NR 37 TC 7 Z9 7 U1 0 U2 3 PU SIAM PUBLICATIONS PI PHILADELPHIA PA 3600 UNIV CITY SCIENCE CENTER, PHILADELPHIA, PA 19104-2688 USA SN 0036-1399 J9 SIAM J APPL MATH JI SIAM J. Appl. Math. PD APR PY 1998 VL 58 IS 2 BP 607 EP 635 DI 10.1137/S0036139996301593 PG 29 WC Mathematics, Applied SC Mathematics GA ZC097 UT WOS:000072539600011 ER PT J AU Goodman, SH Hoven, CW Narrow, WE Cohen, P Fielding, B Alegria, M Leaf, PJ Kandel, D Horwitz, SM Bravo, M Moore, R Dulcan, MK AF Goodman, SH Hoven, CW Narrow, WE Cohen, P Fielding, B Alegria, M Leaf, PJ Kandel, D Horwitz, SM Bravo, M Moore, R Dulcan, MK TI Measurement of risk for mental disorders and competence in a psychiatric epidemiologic community survey: the National Institute of Mental Health methods for the epidemiology of child and adolescent mental disorders (MECA) study SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY LA English DT Article ID CATCHMENT-AREA-PROGRAM; ADDICTIVE-DISORDERS; PUBERTAL STATUS; FAMILY; PSYCHOPATHOLOGY; PREVALENCE; DEPRESSION; MALADJUSTMENT; RELIABILITY; ADJUSTMENT AB This paper describes the implementation of the National Institute of Mental Health Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) study's goals of measuring risk factors and competence. The emphasis is on the development and testing of the measures. Relevant constructs fur measurement of risk and competence in relation to psychopathology wen selected and pilot tested prior to the field trials. A structured interview was developed and field tested using lay interviewers. Using the full sample from the field trials (n = 1285 caretaker-youth pairs), sample means, standard deviations. internal consistencies, parent-youth agreement, and associations with childhood disorder were computed. Descriptive statistics reveal a range of scores and means consistent with norming samples, when available. Internal consistencies were moderate to high. Parent-youth agreement on factual items was excellent and on scales was consistent with the literature. Several strong associations were found between risk factors and disorder, although most were related to disorder in general and not specific to a diagnostic category. This instrument provides a means of obtaining data that will be useful to researchers conducting epidemiologic and clinical studies designed to contribute to the understanding of mental disorders in children and adolescents, including nosology, risk factors, context, adaptive functioning, and treatment. C1 Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. NIMH, Epidemiol & Psychopathol Res Branch, Div Epidemiol & Serv Res, Rockville, MD 20857 USA. Emory Univ, Sch Publ Hlth, Dept Biostat, Atlanta, GA USA. Univ Puerto Rico, Sch Publ Hlth, San Juan, PR 00936 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mental Hyg, Baltimore, MD USA. Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Div Child & Adolescent Psychiat, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Sch Publ Hlth, New York, NY 10032 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. Univ Puerto Rico, Dept Grad Studies Educ, San Juan, PR 00936 USA. Univ Puerto Rico, Behav Sci Res Inst, San Juan, PR 00936 USA. Northwestern Univ, Childrens Mem Hosp, Sch Med, Dept Child & Adolescent Psychiat, Chicago, IL 60614 USA. RP Goodman, SH (reprint author), Emory Univ, Dept Psychol, 532 Kilgo Circle, Atlanta, GA 30322 USA. EM psysg@emory.edu NR 64 TC 102 Z9 102 U1 6 U2 11 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PLATZ DER DEUTSCHEN EINHEIT 25, D-64293 DARMSTADT, GERMANY SN 0933-7954 J9 SOC PSYCH PSYCH EPID JI Soc. Psychiatry Psychiatr. Epidemiol. PD APR PY 1998 VL 33 IS 4 BP 162 EP 173 DI 10.1007/s001270050039 PG 12 WC Psychiatry SC Psychiatry GA ZG573 UT WOS:000073017200004 PM 9567666 ER PT J AU Gresham, GE Kelly-Hayes, M Wolf, PA Beiser, AS Kase, CS D'Agostino, RB AF Gresham, GE Kelly-Hayes, M Wolf, PA Beiser, AS Kase, CS D'Agostino, RB TI Survival and functional status 20 or more years after first stroke - The framingham study SO STROKE LA English DT Article DE stroke outcome; mortality; follow-up studies; case-control studies; epidemiology ID TERM AB Background and Purpose-We examined the 20-or-more-year survival and functional levels of 148 stroke survivors and 148 age-and sex-matched control subjects from the Framingham Study Cohort, whom we originally studied in 1972-1974 to ascertain the survival and disability status of stroke survivors compared with that of controls. Methods-This long-term evaluation was done with use of data from the 1993-1995 Framingham Study Cohort Examination 23 on the 10 stroke survivors and 20 control subjects still living to identify and compare the host characteristics and functional status of each group. The survival curves for both stroke survivors and controls were derived from the ongoing Framingham Study database. Results-Twenty-plus-year stroke survivors experienced a greater mortality than age-and sex-matched controls (92.5% and 81%, respectively), The slopes of the two survival curves were essentially the same. Functional status (eg, walking and independence in activities of daily living) of stroke survivors, however, compared very favorably with that of the control subjects. Stroke survivors were more Likely to be female and to have a number of comorbidities, including elevated blood pressures, greater use of medications, less use of alcohol, and less depressive symptomology. Conclusions-in the Framingham cohort, 20-plus-year stroke survivors showed greater mortality than age-and sex-matched control subjects; functionally, however, the groups were very similar and in general quite independent. C1 SUNY Buffalo, Erie Cty Med Ctr, Dept Rehabil Med, Buffalo, NY 14215 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. Boston Med Ctr, Evans Mem Dept Clin Res, Prevent Med & Epidemiol Sect, Boston, MA USA. Boston Med Ctr, Dept Med, Boston, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Framingham Study Natl Heart Lung & Blood Inst, Framingham, MA USA. RP Gresham, GE (reprint author), SUNY Buffalo, Erie Cty Med Ctr, Dept Rehabil Med, 462 Grider St, Buffalo, NY 14215 USA. FU NHLBI NIH HHS [N01-HC-38038]; NINDS NIH HHS [2R01-NS-17950-15] NR 16 TC 36 Z9 36 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 1998 VL 29 IS 4 BP 793 EP 797 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA ZF529 UT WOS:000072906600009 PM 9550513 ER PT J AU Kase, CS Wolf, PA Kelly-Hayes, M Kannel, WB Beiser, A D'Agostino, RB AF Kase, CS Wolf, PA Kelly-Hayes, M Kannel, WB Beiser, A D'Agostino, RB TI Intellectual decline after stroke The Framingham Study SO STROKE LA English DT Article DE dementia; depression; neuropsychological tests; stroke ID MINI-MENTAL-STATE; WHITE-MATTER LESIONS; BLOOD-PRESSURE; MOOD DISORDERS; RISK-FACTORS; FOLLOW-UP; ALZHEIMERS-DISEASE; COGNITIVE FUNCTION; MAJOR DEPRESSION; ISCHEMIC STROKE AB Background and Purpose-The causes and characteristics of cognitive decline after stroke are poorly defined, because most studies have relied on the diagnosis of dementia after stroke, without measurement of prestroke cognitive function. Methods-The Mini-Mental State Examination (MMSE) was used to assess the cognitive performance of 74 subjects from the Framingham Study cohort who had suffered a stroke during a 13-year period. We compared their poststroke cognitive performance with the prestroke MMSE scores collected during their biennial examinations, and their prestroke/poststroke changes in MMSE score were then compared with those of 74 control subjects matched for age and sex. Cases and controls underwent testing for symptoms of depression using the Center for Epidemiologic Studies of Depression (CES-D) scale, and these findings were correlated with their cognitive performance. Changes in cognitive performance in the cases were correlated with the CT-documented characteristics of the stroke. Results-The cases had a significantly lower mean+/-SE MMSE score at prestroke baseline (27.28+/-0.34) than did the control subjects (28.08+/-0.21), a difference that became more pronounced (23.57+/-0.92 versus 28.31+/-0.25; P<.001) after stroke, The poststroke decline in cognitive function in the cases was correlated only with a large, left-sided stroke on CT. The CES-D scores were significantly higher in the cases, but nondepressed cases had significantly lower MMSE scores than nondepressed controls. Conclusions-Stroke is followed by a significant decline in cognitive performance when prestroke and poststroke measurements are compared. Although depression is more frequent in the stroke patients, their intellectual decline appears to be independent from the presence of depression. C1 Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Biostat & Epidemiol, Boston, MA 02118 USA. Boston Univ, Dept Math, Boston, MA 02118 USA. Framingham Study Natl Heart Lung & Blood Inst, Framingham, MA USA. RP Kase, CS (reprint author), Boston Univ, Sch Med, Dept Neurol, 80 E Concord St,B-605, Boston, MA 02118 USA. FU NHLBI NIH HHS [N01-HC-38038]; NIA NIH HHS [2-RO1-AG08122-08]; NINDS NIH HHS [2-RO1-NS-17950-15] NR 46 TC 94 Z9 99 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 1998 VL 29 IS 4 BP 805 EP 812 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA ZF529 UT WOS:000072906600011 PM 9550515 ER PT J AU Rothman, RB Silverthorn, ML Glowa, JR Matecka, D Rice, KC Carroll, FI Partilla, JS Uhl, GR Vandenbergh, DJ Dersch, CM AF Rothman, RB Silverthorn, ML Glowa, JR Matecka, D Rice, KC Carroll, FI Partilla, JS Uhl, GR Vandenbergh, DJ Dersch, CM TI Studies of the biogenic amine transporters. VII. Characterization of a novel cocaine binding site identified with [I-125]RTI-55 in membranes prepared from human, monkey and guinea pig caudate SO SYNAPSE LA English DT Article DE cocaine; GBR12935; GBR12909; dopamine; benztropine; mazindol; bupropion; nomifensine; transmitter uptake inhibitors neuronal ID HIGH-AFFINITY BINDING; ANALOG I-125 RTI-55; DOPAMINE REUPTAKE INHIBITORS; NOREPINEPHRINE UPTAKE SITES; H-3 MAZINDOL BINDING; RAT-BRAIN; PHENCYCLIDINE-BINDING; NONHUMAN-PRIMATES; NEUROTRANSMITTER TRANSPORTER; SEROTONIN TRANSPORTERS AB [I-125]RTI-55 is a cocaine analog with high affinity for dopamine (DA) and serotonin (5-HT) transporters. Quantitative ligand binding studies revealed a novel high affinity [I-125]RTI-55 binding site assayed under 5-HT transporter (SERT) conditions which has low affinity for almost all classic biogenic amine transporter ligands, including high affinity 5-HT transporter inhibitors such as paroxetine, but which retains high affinity for cocaine analogs. This site, termed SERTsite2 for its detection under 5-HT transporter conditions (not for an association with the SERT) occurs in monkey caudate, human caudate, and guinea pig caudate membranes, but not in rat caudate membranes. SERTsite2 is distinguished from the DA transporter (DAT) and SERT by several criteria, including a distinct ligand-selectivity profile, the inability to detect SERTsite2 in cells stably expressing the cloned human DAT, and insensitivity to irreversible ligands which inhibit [I-125]RTI-55 binding to the DAT and SERT. Perhaps the most striking finding about SERTsite2 is that a nide range of representative antidepressant agents have very low affinity for SERTsite2. The affinity of cocaine for this site is not very different from the concentration cocaine achieves in the brain at pharmacological doses. Viewed collectively with the observation that ligands with high affinity for SERTsite2 are mostly cocaine analogs, these data lead us to speculate that actions of cocaine which differ from those of classic biogenic amine uptake inhibitors may be mediated in part via SERTsite2. (C) 1998 Wiley-Liss, Inc. C1 NIA, Clin Psychopharmacol Sect, DIR, NIH, Baltimore, MD 21224 USA. NIA, Mol Neurobiol Branch, DIR, NIH, Baltimore, MD 21224 USA. NIDDKD, LMC, NIH, Bethesda, MD 20892 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. RP Rothman, RB (reprint author), NIA, Clin Psychopharmacol Sect, DIR, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 93 TC 26 Z9 26 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD APR PY 1998 VL 28 IS 4 BP 322 EP 338 DI 10.1002/(SICI)1098-2396(199804)28:4<322::AID-SYN8>3.0.CO;2-B PG 17 WC Neurosciences SC Neurosciences & Neurology GA ZA012 UT WOS:000072318900008 PM 9517841 ER PT J AU Baumann, MH Rothman, RB AF Baumann, MH Rothman, RB TI Combined phentermine/fenfluramine administration and central serotonin neurons SO SYNAPSE LA English DT Letter ID SUBSTITUTED AMPHETAMINES; D-NORFENFLURAMINE; D-FENFLURAMINE; DEXFENFLURAMINE; MOUSE; BRAIN; RAT; METHAMPHETAMINE; NEUROTOXICITY; TRANSPORTERS C1 NIDA, Intramural Res Program, Lexington, KY 40583 USA. RP Baumann, MH (reprint author), NIDA, Intramural Res Program, Lexington, KY 40583 USA. NR 23 TC 7 Z9 7 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD APR PY 1998 VL 28 IS 4 BP 339 EP 342 PG 4 WC Neurosciences SC Neurosciences & Neurology GA ZA012 UT WOS:000072318900009 PM 9517842 ER PT J AU Yao, ZJ Ye, B Miyoshi, K Otaka, A Burke, TR AF Yao, ZJ Ye, B Miyoshi, K Otaka, A Burke, TR TI Preparation of phospho-L-azatyrosine suitably protected for the synthesis of signal transduction related peptides. A correction SO SYNLETT LA English DT Article DE azatyrosine; phosphotyrosine; signal transduction; solid-phase ID SOLID-PHASE SYNTHESIS; BOC AB Synthesis of N-alpha-Fmoc 4-O,O-(di-tert-butyl)phospho-L-azatyrosine (6) and its use in Fmoc-based solid-phase peptide synthesis are reported. The di-tert-butyl phospho protecting groups were removed during TFA-mediated cleavage of the finished peptide (10) from the resin, providing the free phosphoazatyrosine-containing peptide directly. This is in contrast to diethyl phospho protection we previously reported [Ye, B.; Otaka, A.; Burke, T. R., Jr. Synlett. 1996, 459-460] in which the diethyl protection has proven impractical to remove. Due to incorrect assignment of starting material, the title compound of this latter report should be corrected to the isomeric L-beta-(3-hydroxy-2-pyridyl)-alanine compound (5). C1 NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Kyoto Univ, Fac Pharmaceut Sci, Sakyo Ku, Kyoto 606, Japan. RP Burke, TR (reprint author), NCI, Med Chem Lab, Div Basic Sci, NIH, Bldg 37,Room 5C06, Bethesda, MD 20892 USA. EM tburke@helix.nih.gov RI Burke, Terrence/N-2601-2014; Yao, Zhu-Jun/E-7635-2015 NR 14 TC 3 Z9 3 U1 0 U2 1 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0936-5214 J9 SYNLETT JI Synlett PD APR PY 1998 IS 4 BP 428 EP + PG 4 WC Chemistry, Organic SC Chemistry GA ZL765 UT WOS:000073469300032 ER PT J AU Pacak, K Sweeney, DC Wartofsky, L Mark, AS Punja, U Azzam, CJ Burman, KD AF Pacak, K Sweeney, DC Wartofsky, L Mark, AS Punja, U Azzam, CJ Burman, KD TI Solitary cerebellar metastasis from papillary thyroid carcinoma: A case report SO THYROID LA English DT Article ID DISTANT METASTASES; BONE METASTASES; ONE INSTITUTION; THERAPY; CANCER; MANAGEMENT; IMPACT; BRAIN; LUNG AB Papillary thyroid carcinoma is a common thyroid malignancy that generally has a good prognosis. However, this type of cancer may give rise to distant metastasis and may behave more aggressively in older patients. Here we report clinical, radiological, and pathological findings of a patient with papillary thyroid carcinoma who had a solitary cerebellar metastasis. The patient was known to have metastatic thyroid cancer to the lungs, but this had been stable and the cerebellar metastasis presented an unanticipated significant problem. The rapid detection of cerebellar metastatic disease is critical because neurosurgical removal of the solitary lesion should be considered as the treatment of choice. This case also serves to remind us of the importance of considering possible metastatic brain lesions and their acute life-threatening complications in contrast to the relatively prolonged course associated with metastases of thyroid carcinoma to other organs. C1 Washington Hosp Ctr, Dept Med, Endocrine Sect, Washington, DC 20010 USA. Washington Hosp Ctr, Dept Nucl Med, Washington, DC 20010 USA. Washington Hosp Ctr, Dept Radiol, Washington, DC 20010 USA. Washington Hosp Ctr, Dept Pathol, Washington, DC 20010 USA. Washington Hosp Ctr, Dept Neurosurg, Washington, DC 20010 USA. George Washington Univ, Med Ctr, Washington, DC 20037 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Burman, KD (reprint author), Washington Hosp Ctr, Dept Med, Endocrine Sect, 110 Irving St, Washington, DC 20010 USA. NR 21 TC 18 Z9 18 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD APR PY 1998 VL 8 IS 4 BP 327 EP 335 DI 10.1089/thy.1998.8.327 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZK174 UT WOS:000073292800008 PM 9588498 ER PT J AU Shimada, H Waalkes, MP AF Shimada, H Waalkes, MP TI Treatment with the antiandrogen cyproterone acetate modifies cadmium accumulation and metallothionein induction in C57 and C3H mice SO TOXIC SUBSTANCE MECHANISMS LA English DT Article ID HEPATIC METALLOTHIONEIN; BINDING PROTEINS; SEX-DIFFERENCES; RAT; LIVER; TOXICITY; CARCINOGENESIS; PRETREATMENT; RESISTANCE; AFFINITY AB With the continuing concern over both steroid compounds and metals as potential environmental pollutants, the interactions between these compounds could become an important health issue. In our continuing study of the interactions of cadmium with various steroids we recently found that testosterone pretreatment protects against cadmium-induced toxicity in C57 mice but has no effect in C3H mice. The basis of this strain-specific acquired tolerance to cadmium is still unclear: In this study, we examined the effects of the antiandrogen cyproterone acetate (CA) on the toxicokinetics and toxicity of cadmium and on the ability of cadmium to induce metallothionein (MT) in male C57 and C3H nice. To assess the tissue accumulation of cadmium, the mice were given CA (10 mg/kg, sc, at 48, 24 and 0 h) prior to cadmium (10 mu mol/kg, 0 h). The tissue distribution of cadmium was markedly affected by CA pretreatment, as accumulation of cadmium in liver of both strains was reduced 24 h after cadmium administration. Renal cadmium levels were not affected in either strain by CA. CA pretreatment reduced testicular accumulation of cadmium in C57 mice but not in C3H mice. Cadmium alone, CA alone, or CA and cadmium in combination were not toxic at the doses studied as reflected by the absence of changes in serum glutamic-oxaloacetic transaminase (GOT) activity, lactate dehydrogenase (LDH) activity, and blood urea nitrogen (BUN). CA alone increased MT synthesis in the liver of both strains of mice. However the cadmium-induced MT level in the livers of both strains of mice was markedly decreased by CA pretreatment. In the C57 mice cadmium-induced renal MT levels were also substantially reduced by CA pretreatment but not in the C3H mice. In addition, the levels of cadmium-binding protein within testes were not affected by CA with or without additional cadmium treatment. These results indicate that, despite the fact that CA will itself induce MT in the liver, pretreatment with CA reduces cadmium induction of hepatic and, in some cases, renal MT synthesis. This reduction may be secondary to a reduced accumulation, of cadmium in the liver, but this does not hold true for the kidney. C1 NCI, Frederick Canc Res & Dev Ctr, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. NR 46 TC 1 Z9 1 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 1076-9188 J9 TOX SUBST MECH JI Tox. Subst. Mech. PD APR-JUN PY 1998 VL 17 IS 2 BP 105 EP 119 PG 15 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA ZJ137 UT WOS:000073183200002 ER PT J AU Griffin, RJ Godfrey, VB Burka, LT AF Griffin, RJ Godfrey, VB Burka, LT TI Metabolism and disposition of phenolphthalein in male and female F344 rats and B6C3F1 mice SO TOXICOLOGICAL SCIENCES LA English DT Article ID GLUCURONIDE; HYDROLYSIS AB A recent 2-year carcinogenicity/toxicology study determined that phenolphthalein (PHTH) is a multisite carcinogen in both mice and rats at all doses evaluated. In response to this finding the metabolism and disposition of PHTH has been evaluated in both F344 rats and B6C3F1 mice at a single oral dose of 808 mg/kg, This dose fell within the range previously found to be carcinogenic in rats and mice. Studies were also performed using 1 and 50 mg/kg doses, At 800 mg/kg recovery of [C-14]PHTH after 72 h was near 100% in females but closer to 75% in males. Radioactivity was primarily recovered in the feces in rats (>90%), while mice excreted 30-40% of administered activity in the urine. There was no significant retention of radioactivity in tissues by 72 h and no significant accumulation of radioactivity in any tissue at any time point. Covalent binding to protein in target tissues, bone marrow and ovary, was at or less than the pmol/mg protein range. The major metabolite was PHTH glucuronide. Three minor metabolites were detected. A sulfate conjugate and and a hydroxylated metabolite were identified by comparison of retention times and H-1 NMR and/or mass spectra with synthetic standards. A diglucuronide conjugate was tentatively identified. Biliary elimination was extensive in rats (35% of dose within 6 h); the only product detected in bile was phenolphthalein glucuronide. C1 NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Griffin, RJ (reprint author), NIEHS, Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. NR 18 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD APR PY 1998 VL 42 IS 2 BP 73 EP 81 DI 10.1093/toxsci/42.2.73 PG 9 WC Toxicology SC Toxicology GA ZM173 UT WOS:000073512000001 PM 9579019 ER PT J AU Abdo, KM Haseman, JK Nyska, A AF Abdo, KM Haseman, JK Nyska, A TI Isobutyraldehyde administered by inhalation (whole body exposure) for up to thirteen weeks or two years was a respiratory tract toxicant but was not carcinogenic in F344/N rats and B6C3F(1) mice SO TOXICOLOGICAL SCIENCES LA English DT Article ID REGRESSION-ANALYSIS; FORMALDEHYDE; TESTS; ACETALDEHYDE; TOXICITY AB Isobutyraldehyde (a chemical structurally related to formaldehyde and used as a flavoring agent) was studied for toxicity and carcinogenicity by exposing male and female F344/N rats and B6C3F(1) mice. Animals were exposed to isobutyraldehyde vapors 6 h per day, 5 days per week for up to 13 weeks or 2 years. In the 13-week studies, groups of 10 male and 10 female F344/N rats and B6C3F, mice were exposed to concentrations of 0, 500, 1000, 2000, 4000, or 8000 ppm. Chemical-related body weight depression and deaths occurred in rats and mice exposed to 4000 and 8000 ppm. Necrosis of the epithelium accompanied with acute inflammatory reaction was observed in the nasal turbinate, larynx, and trachea of rats exposed to 8000 ppm. Exposure of rats to 4000 ppm resulted in metaplasia of the nasal respiratory epithelium, inflammation, degeneration of the olfactory epithelium, and osteodystrophy of the nasal turbinate bone. In the 13-week mouse study, exposure to 8000 ppm or 4000 ppm resulted in necrosis of the epithelium lining of the nasal turbinates. Osteodystrophy of the nasal turbinate bone and squamous metaplasia of the nasal respiratory epithelium were noted in mice exposed 4000 ppm. Degeneration of the olfactory epithelium was noted in males exposed 2000 ppm and in females exposed to 4000 ppm. In the 2-year studies, groups of 50 male and 50 male F344/N rats and B6C3F1 were exposed to concentrations isobutyraldehyde vapors of 0, 500, 1000, or 2000 ppm 6 h per day, 5 days per week. There were no differences Fn survival rates or mean body weights between exposed groups and control rats. Survival of male mice exposed to 2000 ppm and mean body weights of female mice exposed to 1000 or 2000 ppm were lower than those of the of the controls. No increase in neoplasm incidence was observed in rats and mice in the 2-year studies that could be attributed to isobutyraldehyde exposure. Chemical-related nonneoplastic lesions were limited to the nose of rats and mice. They included squamous metaplasia of the respiratory epithelium (rats), suppurative inflammation (rats), and olfactory epithelial degeneration (rats and mice) at 1000 and 2000 ppm. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Abdo, KM (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 41 TC 9 Z9 9 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD APR PY 1998 VL 42 IS 2 BP 136 EP 151 DI 10.1006/toxs.1997.2415 PG 16 WC Toxicology SC Toxicology GA ZM173 UT WOS:000073512000008 PM 9579026 ER PT J AU Garner, CE Matthews, HB AF Garner, CE Matthews, HB TI The effect of chlorine substitution on the dermal absorption of polychlorinated biphenyls SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID HUMAN STRATUM-CORNEUM; PARTITION-COEFFICIENTS; SKIN PENETRATION; CHEMICALS; INVITRO; METABOLISM; EXCRETION; EXPOSURE; PCBS; RAT AB The fate of selected mono-, di-, tetra-, and hexachlorobiphenyls was investigated following single dermal administration (0.4 mg/kg) to determine the effects of chlorine substitution on the dermal absorption and disposition of polychlorinated biphenyls (PCBs). Single dermal doses of C-14-labeled mono-, di-, tetra-, and hexachlorobiphenyls were administered to 1-cm(2) areas on the backs of F-344 male rats. Unabsorbed radioactivity was removed from the dose site either at euthanasia or 48 h postdose. Distribution of radioactivity in the dose site and selected tissues was determined by serial sacrifice at time points up to 2 weeks. Dermal penetration varied inversely with degree of chlorination and at 48 h ranged from ca. 100% for monochlorobiphenyl to ca. 30% for the hexachlorobiphenyl. Penetration rate constants correlated well with log K-ow. PCBs were retained in the epidermis for up to 2 weeks postdose, The data from these studies suggest that systemic absorption of PCBs involves a combination of sequential processes including penetration across the stratum corneum, possibly metabolism in the epidermis and/or dermis, adsorption to proteins, and finally absorption into the systemic circulation. The skin favors the rapid absorption of less chlorinated PCBs, but the relatively rapid metabolism and elimination of these compounds would result in lower body burdens. More highly chlorinated PCBs penetrate less rapidly but remain in the site of exposure and slowly enter the systemic circulation. The dermal absorption of a commercial PCB mixture was modeled, and the results suggest that the net result of the differences in absorbance rates would be a greater body burden of higher chlorinated PCBs relative to those that have a lower chlorine content. (C) 1998 Academic Press. C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Garner, CE (reprint author), NIEHS, Lab Pharmacol & Chem, POB 12233, Res Triangle Pk, NC 27709 USA. NR 23 TC 23 Z9 23 U1 2 U2 11 PU ACADEMIC PRESS INC 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 APR PY 1998 VL 149 IS 2 BP 150 EP 158 DI 10.1006/taap.1998.8370 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA ZJ909 UT WOS:000073265900004 PM 9571983 ER PT J AU Klein, HG AF Klein, HG TI Blood, drugs, and the United States pharmacopeia SO TRANSFUSION MEDICINE REVIEWS LA English DT Review C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP Klein, HG (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, 9000 Rockville Pike,Bldg 10 Rom LC711, Bethesda, MD 20892 USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0887-7963 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD APR PY 1998 VL 12 IS 2 BP 81 EP 83 DI 10.1016/S0887-7963(98)80030-8 PG 3 WC Hematology SC Hematology GA ZH227 UT WOS:000073086100001 PM 9566075 ER PT J AU Aravind, L Galperin, MY Koonin, EV AF Aravind, L Galperin, MY Koonin, EV TI The catalytic domain of the P-type ATPase has the haloacid dehalogenase fold SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID SITE-DIRECTED MUTAGENESIS; WILSON-DISEASE; PROTEINS; H+,K+-ATPASE; TRANSPORT; BINDING; COMMON; GENE C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 NR 20 TC 228 Z9 229 U1 2 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD APR PY 1998 VL 23 IS 4 BP 127 EP 129 DI 10.1016/S0968-0004(98)01189-X PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZJ916 UT WOS:000073266600004 PM 9584613 ER PT J AU Kakuta, Y Pedersen, LG Pedersen, LC Niegishi, M AF Kakuta, Y Pedersen, LG Pedersen, LC Niegishi, M TI Conserved structural motifs in the sulfotransferase family SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article C1 Natl Inst Environm Sci, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Sci, Pharmacogenet Sect, Lab Computat Biol, NIH, Res Triangle Pk, NC 27709 USA. RP Kakuta, Y (reprint author), Natl Inst Environm Sci, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 NR 8 TC 116 Z9 118 U1 3 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD APR PY 1998 VL 23 IS 4 BP 129 EP 130 DI 10.1016/S0968-0004(98)01182-7 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZJ916 UT WOS:000073266600005 PM 9584614 ER PT J AU Robbins, J Schneider, AB AF Robbins, J Schneider, AB TI Radioiodine-induced thyroid cancer: Studies in the aftermath of the accident at Chernobyl SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID REACTOR ACCIDENT; MOLECULAR-GENETICS; RET/PTC1 ONCOGENE; RET REARRANGEMENT; NUCLEAR ACCIDENT; HIGH PREVALENCE; POST-CHERNOBYL; P53 GENE; CHILDREN; RADIATION AB While a great deal is known about the relationship between external radiation exposure and thyroid cancer, much less is known about the oncogenic effects of internal radiation exposure from isotopes of iodine. The accident at the Chernobyl nuclear power plant released massive quantities of radioiodine isotopes into the atmosphere. The large number of ensuing thyroid cancers in exposed children leaves little doubt that these malignancies have occurred as a result of the accident. However; carefully planned epidemiological studies ave needed to confirm that these ave due predominantly, to I-131 exposure, to determine the dose-response relationship, to monitor for continuing effects and to evaluate other contributing factors. Preliminary evidence indicates that there is a distinct pattern of somatic genetic changes in the thyroid cancers from the Chernobyl area. C1 NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. Univ Illinois, Coll Med, Dept Med, Sect Endocrinol & Metab, Chicago, IL 60612 USA. RP Robbins, J (reprint author), NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. NR 49 TC 15 Z9 15 U1 1 U2 3 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD APR PY 1998 VL 9 IS 3 BP 87 EP 94 DI 10.1016/S1043-2760(98)00024-1 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZU314 UT WOS:000074184300001 PM 18406248 ER PT J AU Hu, ZZ Zhuang, L Dufau, ML AF Hu, ZZ Zhuang, L Dufau, ML TI Prolactin receptor gene diversity: Structure and regulation SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID BREAST-CANCER CELLS; MAMMARY-GLAND; RAT-LIVER; LONG FORM; TRANSCRIPTIONAL REGULATION; GROWTH-HORMONE; CHOROID-PLEXUS; MESSENGER-RNA; ESTROUS-CYCLE; PRL RECEPTOR AB The diverse functionality of prolactin and the wide expression of the prolactin receptor suggest a complex system regulated by this polypeptide hormone. Different hormone and receptor forms, as well as differential signal transduction pathways, contribute to the functional diversity of prolactin's actions. The heterogeneity of rat prolactin receptor gene transcripts in their 5'-untranslated region has led to the recognition of multiple and tissue-specific utilization of prolactin receptor gene promoters in gonadal and non-gonadal tissues. These findings have provided insights into the molecular basis for the diversity of prolactin's actions. It is now clear that cellular responsiveness to prolactin can be regulated through differential promoter control of the expression of the surface receptors for prolactin in different target tissues. C1 NICHHD, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, Bethesda, MD 20892 USA. RP Hu, ZZ (reprint author), NICHHD, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, Bethesda, MD 20892 USA. NR 65 TC 22 Z9 22 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD APR PY 1998 VL 9 IS 3 BP 94 EP 102 DI 10.1016/S1043-2760(98)00027-7 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZU314 UT WOS:000074184300002 PM 18406249 ER PT J AU Dawid, IB Breen, JJ Toyama, R AF Dawid, IB Breen, JJ Toyama, R TI LIM domains: multiple roles as adapters and functional modifiers in protein interactions SO TRENDS IN GENETICS LA English DT Review ID CYSTEINE-RICH PROTEIN; HOMEOBOX GENE LHX3; CELL LINEAGES; HOMEODOMAIN; EXPRESSION; BINDING; XENOPUS; XLIM-1; MOTIF; DIFFERENTIATION AB The LIM domain is a specialized double-zinc finger motif found in a variety of proteins, in association with domains of divergent functions or forming proteins composed primarily of LIM domains. LIM domains interact specifically with other LIM domains and with many different protein domains. LIM domains are thought to function as protein interaction modules, mediating specific contacts between members of functional complexes and modulating the activity of some of the constituent proteins. Nucleic acid binding by LIM domains, while suggested by structural considerations, remains an unproven possibility. LIM-domain proteins can be nuclear, cytoplasmic, or can shuttle between compartments. Several important LIM proteins are associated with the cytoskeleton, having a role in adhesion-plaque and actin-microfilament organization. Among nuclear LIM proteins, the LIM homeodomain proteins form a major subfamily with important functions in cell lineage determination and pattern formation during animal development. C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Dawid, IB (reprint author), NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. EM idawid@nih.gov; breenj@nih.gov; reiko@nih.gov NR 85 TC 447 Z9 461 U1 3 U2 14 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD APR PY 1998 VL 14 IS 4 BP 156 EP 162 DI 10.1016/S0168-9525(98)01424-3 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA ZG656 UT WOS:000073025900009 PM 9594664 ER PT J AU Wen, H Wiesler, DG Tveten, A Danver, B Dandridge, A AF Wen, H Wiesler, DG Tveten, A Danver, B Dandridge, A TI High-sensitivity fiber-optic ultrasound sensors for medical imaging applications SO ULTRASONIC IMAGING LA English DT Article DE electromagnetic interference; laser interferometer; optical fiber; ultrasound sensor AB This paper presents several designs of high-sensitivity, compact fiber-optic ultrasound sensors that may be used for medical imaging applications. These sensors translate ultrasonic pulses into strains in single-mode optical fibers, which are measured with fiber-based laser interferometers at high precision. The sensors are simpler and less expensive to make than piezoelectric sensors, and are not susceptible to electromagnetic interference. It is possible to make focal sensors with these designs, and several schemes are discussed. Because of the minimum bending radius of optical fibers, the designs are suitable for single element sensors rather than for arrays. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. USN, Res Lab, Div Opt Sci, Washington, DC 20375 USA. RP Wen, H (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RI Wen, Han/G-3081-2010 OI Wen, Han/0000-0001-6844-2997 FU Intramural NIH HHS [Z01 HL004606-12] NR 8 TC 10 Z9 10 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0161-7346 J9 ULTRASONIC IMAGING JI Ultrason. Imaging PD APR PY 1998 VL 20 IS 2 BP 103 EP 112 PG 10 WC Acoustics; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 104GL UT WOS:000075006300002 PM 9691368 ER PT J AU Wu, J Adomat, JM Ridky, TW Louis, JM Leis, J Harrison, RW Weber, IT AF Wu, J Adomat, JM Ridky, TW Louis, JM Leis, J Harrison, RW Weber, IT TI Structural basis for specificity of retroviral proteases SO BIOCHEMISTRY LA English DT Article ID ROUS-SARCOMA VIRUS; SUBSTRATE-BINDING POCKETS; HUMAN-IMMUNODEFICIENCY; HIV-1 PROTEASE; CRYSTAL-STRUCTURES; ASPARTIC PROTEASE; INHIBITOR; TYPE-1; PROTEINASES; RESOLUTION AB The Rous sarcoma virus (RSV) protease S9 variant has been engineered to exhibit high affinity for HIV-1 protease substrates and inhibitors in order to verify the residues deduced to be critical for the specificity differences. The variant has 9 substitutions (S38T, I42D, I44V, M73V, A100L, V104T, R105P, G106V, and S107N) of structurally equivalent residues from HIV-1 protease, Unlike the wild-type enzyme, RSV S9 protease hydrolyzes peptides representing the HIV-1 protease polyprotein cleavage sites. The crystal structure of RSV S9 protease with the inhibitor, Arg-Val-Leu-r-Phe-Glu-Ala-Nle-NH2, a reduced peptide analogue of the HIV-1 CA-p2 cleavage site, has been refined to an R factor of 0.175 at 2.4-Angstrom resolution. The structure shows flap residues that were not visible in the previous crystal structure of unliganded wild-type enzyme. Flap residues 64-76 are structurally similar to residues 47-59 of HIV-1 protease. However, residues 61-63 form unique loops at the base of the flaps. Mutational analysis indicates that these loop residues are essential for catalytic activity. Side chains of flap residues His 65 and Gin 63' make hydrogen bond interactions with the inhibitor P3 amide and P4' carbonyl oxygen, respectively. Other interactions of RSV S9 protease with the CA-p2 analogue are very similar to those observed in the crystal structure of HIV-1 protease with the same inhibitor. This is the first crystal structure of an avian retroviral protease in complex with an inhibitor, and it verifies our knowledge of the molecular basis for specificity differences between RSV and HIV-1 proteases. C1 Thomas Jefferson Univ, Dept Microbiol & Immunol, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA. NIDDKD, Mol Mechanisms Dev Sect, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Weber, IT (reprint author), Thomas Jefferson Univ, Dept Microbiol & Immunol, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. OI Ridky, Todd/0000-0001-8482-1284 FU NCI NIH HHS [CA52047, CA58166]; NIAID NIH HHS [AI41380]; NIGMS NIH HHS [R01 GM062920] NR 28 TC 34 Z9 37 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 31 PY 1998 VL 37 IS 13 BP 4518 EP 4526 DI 10.1021/bi972183g PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZG874 UT WOS:000073048700024 PM 9521772 ER PT J AU Shahabuddin, M Pimenta, PFP AF Shahabuddin, M Pimenta, PFP TI Plasmodium gallinaceum preferentially invades vesicular ATPase-expressing cells in Aedes aegypti midgut SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TOBACCO HORNWORM MIDGUT; SECONDARY ACTIVE-TRANSPORT; INSECT V-ATPASE; PROTON PUMP; MALPIGHIAN TUBULES; EPITHELIAL-CELLS; MOSQUITO MIDGUT; ENDOCRINE-CELLS AB Penetration of the mosquito midgut epithelium is obligatory for the further development of Plasmodium parasites, Therefore, blocking the parasite from invading the midgut wall disrupts the transmission of malaria, Despite such a pivotal role in malaria transmission, the cellular and molecular interactions that occur during the invasion are not understood, Here, we demonstrate that the ookinetes of Plasmodium gallinaceum, which is related closely to the human malaria parasite Plasmodium falciparum, selectively invade a cell type in the Aedes aegypti midgut, These cells, unlike the majority of the cells in the midgut, do not stain with a basophilic dye (toluidine blue) and are less osmiophilic. In addition, they contain minimal endoplasmic reticulum, lack secretory granules, and have few microvilli, Instead, these cells are highly vacuolated and express large amounts of vesicular ATPase, The enzyme is associated with the apical plasma membrane, cytoplasmic vesicles, and tubular extensions of the basal membrane of the invaded cells, The high cost of insecticide use in endemic areas and the emergence of drug resistant malaria parasites call for alternative approaches such as modifying the mosquito to block the transmission of malaria, One of the targets for such modification is the parasite receptor on midgut cells, A step toward the identification of this receptor is the realization that malaria parasites invade a special cell type in the mosquito midgut. C1 NIAID, Med Entomol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Fdn Oswaldo Cruz, Ctr Pesquisas Rene Rachou, Lab Med Entomol, BR-30190002 Belo Horizonte, MG, Brazil. RP Shahabuddin, M (reprint author), NIAID, Med Entomol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 24 TC 57 Z9 58 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 31 PY 1998 VL 95 IS 7 BP 3385 EP 3389 DI 10.1073/pnas.95.7.3385 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZE957 UT WOS:000072848500015 PM 9520375 ER PT J AU Yang, X Li, CL Xu, XL Deng, CX AF Yang, X Li, CL Xu, XL Deng, CX TI The tumor suppressor SMAD4/DPC4 is essential for epiblast proliferation and mesoderm induction in mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gastrulation; gene targeting; transforming growth factor beta signaling ID TGF-BETA SUPERFAMILY; DPC4 GENE; MAD PROTEINS; IN-VIVO; MOUSE; GASTRULATION; RECEPTOR; GROWTH; SIGNALS; DIFFERENTIATION AB Members of the transforming growth factor (TGF)-beta superfamily have been shown to play a variety of important roles in embryogenesis, including dorsal and ventral mesoderm induction, The tumor suppressor SMAD4, also known as DPC4, is believed to be an essential factor that mediates TGF-beta signals, To explore functions of SMAD4 in development, we have mutated it by truncating its functional C-domain, We show that Smad4 is expressed ubiquitously during murine embryogenesis, Mice heterozygous for the Smad(4ex8/+) mutation are developmentally normal, whereas homozygotes die between embryonic day 6.5 (E6.5) and 8.5. All Smad(4ex8/ex8) mutants are developmentally delayed at E6 and show little or no elongation in the extraembryonic portion of late egg cylinder stage embryos, Consistent with this, cultured Smad(4ex8/ex8) blastocyst outgrowths suffer cellular proliferation defects and fail to undergo endoderm differentiation. Although a portion of mutant embryos at E8.5 show an increase in the embryonic ectoderm and endoderm, morpho logical and molecular analyses Indicate that they do not form mesoderm, Altogether, these data demonstrate that SMAD4-mediated signals are required for epiblast proliferation, egg cylinder formation, and mesoderm induction. C1 NIDDKD, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA. RP Deng, CX (reprint author), NIDDKD, Biochem & Metab Lab, NIH, 10-9N105, Bethesda, MD 20892 USA. RI deng, chuxia/N-6713-2016 NR 41 TC 201 Z9 216 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 31 PY 1998 VL 95 IS 7 BP 3667 EP 3672 DI 10.1073/pnas.95.7.3667 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZE957 UT WOS:000072848500063 PM 9520423 ER PT J AU Zhang, JZ Rosenberg, HF Nei, M AF Zhang, JZ Rosenberg, HF Nei, M TI Positive Darwinian selection after gene duplication in primate ribonuclease genes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ancestral sequence; anti-pathogenic function; rapid evolution; synonymous and nonsynonymous substitution ID EOSINOPHIL CATIONIC PROTEIN; NONSYNONYMOUS SUBSTITUTIONS; RAPID EVOLUTION; NUCLEOTIDE; NUMBERS; RATES; SEQUENCES; SUPERFAMILY; DROSOPHILA; NEUROTOXIN AB Evolutionary mechanisms of origins of new gene function have been a subject of long-standing debate, Here we report a convincing case in which positive Darwinian selection operated at the molecular level during the evolution of novel function by gene duplication, The genes for eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) in primates belong to the ribonuclease gene family, and the ECP gene, whose product has an anti-pathogen function not displayed by EDN, was generated by duplication of the EDN gene about 31 million years ago, Using inferred nucleotide sequences of ancestral organisms, we showed that the rate of nonsynonymous nucleotide substitution was significantly higher than that of synonymous substitution for the ECP gene, This strongly suggests that positive Darwinian selection operated in the early stage of evolution of the ECP gene, It was also found that the number of arginine residues increased substantially in a short period of evolutionary time after gene duplication, and these amino acid changes probably produced the novel anti-pathogen function of ECP. C1 Penn State Univ, Inst Mol Evolutionary Genet, Mueller Lab 328, University Pk, PA 16802 USA. Penn State Univ, Dept Biol, University Pk, PA 16802 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Nei, M (reprint author), Penn State Univ, Inst Mol Evolutionary Genet, Mueller Lab 328, University Pk, PA 16802 USA. EM nxm2@psu.edu NR 55 TC 531 Z9 549 U1 1 U2 17 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 31 PY 1998 VL 95 IS 7 BP 3708 EP 3713 DI 10.1073/pnas.95.7.3708 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZE957 UT WOS:000072848500071 PM 9520431 ER PT J AU Liang, H Fairman, J Claxton, DF Nowell, PC Green, ED Nagarajan, L AF Liang, H Fairman, J Claxton, DF Nowell, PC Green, ED Nagarajan, L TI Molecular anatomy of chromosome 7q deletions in myeloid neoplasms: Evidence for multiple critical loci SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE instability; unbalanced translocation; monosomy; leukemia ID TUMOR-SUPPRESSOR GENE; BREAST-CANCER; SQUAMOUS-CELL; FREQUENT LOSS; HETEROZYGOSITY; CARCINOMAS; LEUKEMIA; REGION; 7Q31.1; HUMAN-CHROMOSOME-7 AB Complete or partial deletions of the long arm of chromosome 7 (7q- and -7) are nonrandom abnormalities seen in primary and therapy-induced myelodysplasia (MDS) and acute myelogenous leukemia (AML), Monosomy 7, occurring as the sole cytogenetic anomaly in a small but significant number of cases, may denote a dominant mechanism involving critical tumor suppressor gene(s), We have determined the extent of allele loss in cytogenetically prescreened MDS and AML patients for microsatellite markers from chromosome 7q22 and 7q31, Whereas >80% of these cases revealed allele loss for the entire region, a rare case off the 7q-chromosome showed allele loss for only the proximal 7q31.1 loci flanked by the markers D7S486 and D7S2456, and a case of monosomy 7 revealed allele loss for loci at both 7q31. and 7q22 with retention of sequences between these sees of loci, Furthermore, a case of AML with no cytogenetic anomaly of chromosome 7 revealed a submicroscopic allelic imbalance for a third distal locus, D7S677, These findings suggest the presence of three distinct critical loci that may contribute alone or in combination to the evolution of MDS and AML. The data also provide molecular evidence for unbalanced translocation with noncontiguous deletions, as an alternate mechanism underlying monosomy 7. C1 Univ Texas, MD Anderson Cancer Ctr, Dept Mol Hematol & Therapy, Houston, TX 77030 USA. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. NIH, Genome Technol Branch, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. RP Nagarajan, L (reprint author), Univ Texas, MD Anderson Cancer Ctr, Dept Mol Hematol & Therapy, 1515 Holcombe Blvd,Box 81, Houston, TX 77030 USA. FU NCI NIH HHS [P01 CA055164, CA 42232, P30 CA016672, CA 55164, CA16672] NR 35 TC 112 Z9 113 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 31 PY 1998 VL 95 IS 7 BP 3781 EP 3785 DI 10.1073/pnas.95.7.3781 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZE957 UT WOS:000072848500084 PM 9520444 ER PT J AU Kuo, CL Chen, ML Wang, K Chou, CK Vernooij, B Seto, D Koop, BF Hood, L AF Kuo, CL Chen, ML Wang, K Chou, CK Vernooij, B Seto, D Koop, BF Hood, L TI A conserved sequence block in murine and human T cell receptor (TCR) J alpha region is a composite element that enhances TCR alpha enhancer activity and binds multiple nuclear factors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRANSCRIPTION FACTOR PU.1; B-CELL; POU DOMAIN; MOLECULAR-GENETICS; PROTEIN-BINDING; DNA RECOGNITION; DELTA REGION; GENES; SITE; IMMUNOGLOBULIN AB A conserved sequence block (CSB) located in a noncoding region of the mouse and human TCR alpha/delta loci, showing six differences over 125 nucleotide positions (95% similar), was subjected to detailed analyses in this study, Transient transfection results showed that the CSB-containing element in conjunction with the TCR alpha enhancer up-regulated the alpha enhancer activity, whereas no enhancer activity was detected when CSB alone was assayed. In vitro occupancy analyses of CSB by nuclear factors reveal the existence of an unexpectedly intricate network of CSB-protein and protein-protein interactions, Lymphoid-specific as well as T-lineage-specific nuclear factors are involved to differentially form CSB-bound complexes in extracts of various tissues and cell lines. Liver was shown to contain factor(s) sequestering thymic CSB-binding factors, Furthermore, the putative binding sites for transcription factors known to be important for lymphoid-lineage development are present in CSR and are targeted by nuclear factors, On the basis of these results, we propose that the CSB element may play a role in shaping the chromatin structure by which the accessibility of TCR alpha/delta loci to the recombinase complex and/or to the transcriptional apparatus can be controlled. C1 Natl Taiwan Univ, Coll Sci, Inst Biochem Sci, Taipei 10764, Taiwan. Univ Washington, Sch Med, Dept Mol Biotechnol, Seattle, WA 98195 USA. Univ Victoria, Dept Biol, Ctr Environm Hlth, Victoria, BC V8W 2Y2, Canada. NIH, Div Endocrinol, Bethesda, MD 20892 USA. RP Kuo, CL (reprint author), Natl Taiwan Univ, Coll Sci, Inst Biochem Sci, POB 23-106, Taipei 10764, Taiwan. EM chialam@ccms.ntu.edu.tw RI Koop, Ben/A-8151-2008 OI Koop, Ben/0000-0003-0045-5200 NR 36 TC 12 Z9 12 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 31 PY 1998 VL 95 IS 7 BP 3839 EP 3844 DI 10.1073/pnas.95.7.3839 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZE957 UT WOS:000072848500094 PM 9520454 ER PT J AU Migone, TS Cacalano, NA Taylor, N Yi, TL Waldmann, TA Johnston, JA AF Migone, TS Cacalano, NA Taylor, N Yi, TL Waldmann, TA Johnston, JA TI Recruitment of SH2-containing protein tyrosine phosphatase SHP-1 to the interleukin 2 receptor; loss of SHP-1 expression in human T-lymphotropic virus type I-transformed T cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IL-2 RECEPTOR; BETA-CHAIN; SIGNAL-TRANSDUCTION; GAMMA(C) CHAIN; HTLV-I; KINASE; ASSOCIATION; ACTIVATION; PHOSPHORYLATION; PATHWAY AB Interleukin 2 (IL-2) rapidly induces tyrosine phosphorylation of intracellular substrates, including the IL-2 receptor beta chain (IL-2R beta), Janus kinase 1 (Jak1), Jak3, signal transducer/activator of transcription proteins, and Shc, but the mechanism underlying dephosphorylation of these proteins is not known, The src homology 2 (SH2) containing tyrosine phosphatase 1 (SHP-1) is recruited by several hematopoietic surface receptors indicating that this phosphatase plays an important role as a regulator of signaling, We have found that IL-2 induces association of SHP-1 with the IL-2 receptor complex, and that once SHP-1 is recruited to the activated receptor it is able to decrease tyrosine phosphorylation of IL-2R beta and the associated tyrosine kinases Jak1 and Jak3, This dephosphorylation is specific as expression of a catalytically inactive form of SHP-1, or expression of the related phosphatase SHP-2 did not result In dephosphorylation of the IL-2 receptor components, Furthermore, we have found that SHP-1 expression is greatly decreased or undetectable in a number of IL-2 independent HTLV-1 transformed T cell lines that exhibit constitutive Jak/signal transducer/activator of transcription activation, In HTLV-I infected T cells, down-regulation of SHP-1 expression was also found to correlate with the acquisition of IL-2 independence. These observations suggest that SHP-1 normally functions to antagonize the IL-2 signal transduction pathway and that HTLV-1 infection and oncogenic transformation can lead to loss of SHP-1 expression resulting in constitutive activation of IL-2 regulated T cell responses. C1 DNAX Res Inst Mol & Cellular Biol Inc, Palo Alto, CA 94304 USA. Inst Genet Mol Montpellier, Montpellier, France. Cleveland Clin Fdn, Res Inst, Dept Canc Biol, Cleveland, OH 44195 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Migone, TS (reprint author), DNAX Res Inst Mol & Cellular Biol Inc, 901 Calif Ave, Palo Alto, CA 94304 USA. EM migone@dnax.org NR 30 TC 94 Z9 98 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 31 PY 1998 VL 95 IS 7 BP 3845 EP 3850 DI 10.1073/pnas.95.7.3845 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZE957 UT WOS:000072848500095 PM 9520455 ER PT J AU Zagury, D Lachgar, A Chams, V Fall, LS Bernard, J Zagury, JF Bizzini, B Gringeri, A Santagostino, E Rappaport, J Feldman, M O'Brien, SJ Burny, A Gallo, RC AF Zagury, D Lachgar, A Chams, V Fall, LS Bernard, J Zagury, JF Bizzini, B Gringeri, A Santagostino, E Rappaport, J Feldman, M O'Brien, SJ Burny, A Gallo, RC TI C-C chemokines, pivotal in protection against HIV type 1 infection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NON-B HEPATITIS; HIGH-RISK; RECEPTOR; GENE; MIP-1-ALPHA; RESISTANCE; PROTEIN; CELLS; CCR-5; INDIVIDUALS AB Exposure to HIV type 1 (HIV-1) does not usually lead to infection, Although this could be because of insufficient virus titer, there is now abundant evidence that some individuals resist infection even when directly exposed to a high titer of HIV, This protection recently has been correlated with homozygous mutations of an HIV-1 coreceptor, namely CCR5, the receptor for the beta-chemokines, Moreover, earlier results already had shown that the same chemokines markedly suppress the nonsyncitial inducing variants of HIV-1, the chief virus type transmitted from person to person, CCR5 mutation, as a unique mechanism of protection, is, however, suspect because HIV-1 variants can use other chemokine receptors as their coreceptor. Moreover, recent results have established that infection can indeed sometimes occur with such mutations, Here, we report on transient natural resistance over time of most of 128 hemophiliacs who were inoculated repeatedly with HIV-1-contaminated Factor VIII concentrate from plasma during 1980-1985 before the development of the HIV blood test, Furthermore, and remarkably, 14 subjects remain uninfected to this date, and in these subjects we found homozygous CCR5 mutations in none but in most of them overproduction of beta chemokines, In vitro experiments confirmed the potent anti-HIV suppressive effect of these chemokines. C1 Univ Maryland, Inst Biotechnol, Inst Human Virol, Baltimore, MD 21201 USA. Univ Libre Bruxelles, B-1050 Brussels, Belgium. NCI, Frederick, MD 21702 USA. Weizmann Inst Sci, IL-76100 Rehovot, Israel. Allegheny Univ Hlth Sci, Ctr Neurovirol & Neurooncol, Philadelphia, PA 19102 USA. Univ Milan, I-20122 Milan, Italy. Maggiore Hosp, IRCCS, A Bianchi Bonomi Hemophilia & Thrombosis Ctr, Bologna, Italy. Inst Jean Godinoi, F-51100 Reims, France. Univ Pierre & Marie Curie, Paris, France. RP Gallo, RC (reprint author), Univ Maryland, Inst Biotechnol, Inst Human Virol, 725 W Lombard St, Baltimore, MD 21201 USA. NR 30 TC 163 Z9 168 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 31 PY 1998 VL 95 IS 7 BP 3857 EP 3861 DI 10.1073/pnas.95.7.3857 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZE957 UT WOS:000072848500097 PM 9520457 ER PT J AU Gaxiola, RA Yuan, DS Klausner, RD Fink, GR AF Gaxiola, RA Yuan, DS Klausner, RD Fink, GR TI The yeast CLC chloride channel functions in cation homeostasis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SACCHAROMYCES-CEREVISIAE ENCODES; IRON UPTAKE; COPPER TRANSPORT; GENE; VESICLES; PROTEIN AB A defect in the yeast GEF1 gene, a CLC chloride channel homolog leads to an iron requirement and cation sensitivity, The iron requirement is due to a failure to load Cu2+ onto a component of the iron uptake system, Fet3, This profess, which requires both Gef1 and the Menkes disease Cu2+-ATPase yeast homolog Ccc2, occurs in late-or post-Golgi vesicles, where Gef1 and Ccc2 are localized, The defects of gef1 mutants can be suppressed by the introduction of Torpedo marmorata CLC-0 or arabidopsis thaliana CLC-c and -d chloride channel genes, The functions of Gef1 in cation homeostasis provide clues to the understanding of diseases caused by chloride channel mutations in humans and cation toxicity in plants. C1 MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. NCI, Off Director, NIH, Bethesda, MD 20892 USA. RP MIT, Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. FU NIGMS NIH HHS [R01 GM035010, GM35010] NR 28 TC 123 Z9 128 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 31 PY 1998 VL 95 IS 7 BP 4046 EP 4050 DI 10.1073/pnas.95.7.4046 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZE957 UT WOS:000072848500130 PM 9520490 ER PT J AU Bell, JA Grant, SJ AF Bell, JA Grant, SJ TI Locus coeruleus neurons from morphine-treated rats do not show opiate-withdrawal hyperactivity in vitro SO BRAIN RESEARCH LA English DT Article DE locus coeruleus; morphine; opiate dependence; naloxone; brain slice ID BRAIN-SLICES; DEPENDENT RATS; CERULEUS NEURONS; TOLERANCE; MECHANISMS; CLONIDINE; CELL AB In vitro studies have not consistently demonstrated naloxone-precipitated opiate-withdrawal hyperactivity of locus coeruleus neurons. The reason for this inconsistency may be because partial or complete withdrawal occurred during preparation of the locus coeruleus slice. The aim of the present study was to assay opiate withdrawal-related hyperactivity in neurons recorded from locus coeruleus slices while ensuring the maintenance of dependence until naloxone-precipitated withdrawal. Extracellular recordings were obtained from individual locus coeruleus neurons in slices from morphine-treated and drug-naive rats. Morphine 1 mu M was present in all solutions during preparation and recording in slices from morphine-treated rats. The average firing rate of the drug-naive controls was 0.93 Hz (+/- 0.04 Hz). Bath application of morphine (1 mu M) almost completely suppressed firing in drug-naive controls (0.058 Hz, +/- 0.04 Hz, n = 12), whereas in solutions containing 1 mu M morphine, the firing rate of cells from morphine-treated rats averaged 0.71 Hz (+/- 0.05 Hz), indicating considerable, but incomplete tolerance. In the same slices, naloxone increased the average spontaneous firing of locus coeruleus cells to 0.96 Hz (+/- 0.04 Hz). Thus, naloxone did not produce withdrawal hyperactivity, but returned the cells from morphine-treated rats to control rates. We conclude that locus coeruleus cells in locus coeruleus slice preparations from morphine-treated rats did not demonstrate withdrawal-related hyperactivity even when dependence was maintained until naloxone-precipitated withdrawal. Thus, our results do not support a role for adaptations intrinsic to locus coeruleus neurons in withdrawal hyperexcitability, but instead imply the necessity of functional afferent activity. (C) 1998 Elsevier Science B.V. C1 NIDA, Brain Imaging Sect, Neurosci Branch, Intramural Res Program, Baltimore, MD 21224 USA. RP Bell, JA (reprint author), NIDA, Brain Imaging Sect, Neurosci Branch, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 27 TC 10 Z9 10 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 MAR 30 PY 1998 VL 788 IS 1-2 BP 237 EP 244 DI 10.1016/S0006-8993(98)00003-1 PG 8 WC Neurosciences SC Neurosciences & Neurology GA ZM870 UT WOS:000073584600031 PM 9555033 ER PT J AU Kucera, J Fan, GP Walro, J Copray, S Tessarollo, L Jaenisch, R AF Kucera, J Fan, GP Walro, J Copray, S Tessarollo, L Jaenisch, R TI Neurotrophin-3 and trkC in muscle are non-essential for the development of mouse muscle spindles SO NEUROREPORT LA English DT Article DE growth factors; muscle spindle; neurotrophin-3; proprioception; transgenic mice; TrkC ID NEONATAL RATS; AFFERENTS; EXPRESSION; NEURONS; MICE AB NEUROTROPHIN-3 (NT3) or TrkC null mutant mice were examined for the presence of muscle spindles. Muscles of mastication, but not limbs, contained spindles in newborn and adolescent mutants. The intramuscular distribution and morphological properties of spindles in mutant masticatory muscles were indistinguishable from those of wild-type spindles. Intrafusal fibers of NT3- or trkC-deficient spindles expressed the slow-tonic isoform of myosin heavy chains, characteristic of wild-type spindles. Sensory nerve endings were observed in spindles of mutants by electron microscopy. Thus, NT3 or trkC, which is expressed in wild-type spindles, may serve functions other than those related to spindle assembly. Presumably, proprioceptive neurons innervating jaw muscles are dependent on factors other than NT3 for survival and maintenance. (C) 1998 Rapid Science Ltd. C1 Neurol Res 151, Boston, MA 02130 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. MIT, Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. NE Ohio Univ, Coll Med, Dept Anat, Rootstown, OH 44272 USA. Univ Groningen, Dept Med Physiol, Groningen, Netherlands. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Neural Dev Grp, Frederick, MD 21702 USA. RP Kucera, J (reprint author), Neurol Res 151, 150 S Huntingdon Ave, Boston, MA 02130 USA. OI Fan, Guoping/0000-0001-5235-6410 FU NINDS NIH HHS [R01 NS25796] NR 23 TC 15 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAR 30 PY 1998 VL 9 IS 5 BP 905 EP 909 DI 10.1097/00001756-199803300-00026 PG 5 WC Neurosciences SC Neurosciences & Neurology GA ZE584 UT WOS:000072808900026 PM 9579688 ER PT J AU Berger, EA AF Berger, EA TI Hot papers - Virology - HIV-1 entry cofactor: Functional cDNA cloning of a 7-transmembrane G protein-coupled receptor by Y. Feng, C.C. Broder, P.E. Kennedy, E.A. Berger - Comments SO SCIENTIST LA English DT Editorial Material ID CHEMOKINE AB HOT papers: Virologist Edward A. Berger discusses the impact of fusin on understanding the path of HIV. C1 NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RP Berger, EA (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD MAR 30 PY 1998 VL 12 IS 7 BP 11 EP 11 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA ZD727 UT WOS:000072717400012 ER PT J AU Feng, JN Sobell, JL Heston, LL Cook, EH Goldman, D Sommer, SS AF Feng, JN Sobell, JL Heston, LL Cook, EH Goldman, D Sommer, SS TI Scanning of the dopamine D1 and D5 receptor genes by REF in neuropsychiatric patients reveals a novel missense change at a highly conserved amino acid SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE dopamine receptor; schizophrenia; autism; attention deficit hyperactivity disorder; alcoholism ID CANDIDATE-GENE; MUTATIONS; IDENTIFICATION; SCHIZOPHRENIA; ASSOCIATION; POLYMORPHISMS; ALCOHOLICS; CLONING; DNA; PREDISPOSITION AB In previous analyses of schizophrenic patients, multiple missense changes and one nonsense change were identified in the D5 dopamine receptor (DRD5) gene, but no sequence changes of likely functional significance were identified in the D1 dopamine receptor (DRD1) gene. In the present study, we examined these genes in patients with certain other neuropsychiatric disorders that may be related to dopaminergic dysregulation. The coding regions of the DRD1 and DRD5 genes were examined in 25 and 25 autistic patients, 25 and 28 attention deficit hyperactivity disorder patients, and 51 and 43 alcoholic patients, respectively. In addition, the DRD5 gene was examined in 75 schizophrenic patients to search for additional variants affecting protein structure or expression (VAPSEs). These patients were analyzed with REF (restriction endonuclease fingerprinting), a hybrid between SSCP and restriction endonuclease digestion, which allows the entire coding sequence to be screened in one lane of a gel. Approximately 800 kb of genomic sequence were examined. No sequence changes were identified in the DRD1 gene among the 101 patient samples analyzed. Two sequence changes were identified in the DRD5 gene among the 171 patient samples. These included one previously identified silent polymorphism at base pair 978 (P326P). The change was identified in patients from all disease categories and from different ethnic backgrounds. One novel missense change, L88F, occurred in transmembrane domain II at a highly conserved amino acid in all dopamine receptors as well as in alpha 1- and beta-adrenergic receptors. The mutation was identified in a Caucasian male patient with autism. Further analysis is necessary to determine if this missense change is associated with a particular neuropsychiatric phenotype. (C) 1998 Wiley-Liss, Inc. C1 City Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Diagnosis, Div Human Genet, Duarte, CA 91010 USA. Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. NIAAA, Rockville, MD 20852 USA. City Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Diagnosis, Div Human Genet, Duarte, CA 91010 USA. RP Sommer, SS (reprint author), City Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Diagnosis, Div Human Genet, Duarte, CA 91010 USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU NIMH NIH HHS [MH44276, KO MH01389, MH52223] NR 39 TC 32 Z9 32 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAR 28 PY 1998 VL 81 IS 2 BP 172 EP 178 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA ZL510 UT WOS:000073440800009 PM 9613858 ER PT J AU Smith, ACM Dykens, E Greenberg, F AF Smith, ACM Dykens, E Greenberg, F TI Behavioral phenotype of Smith-Magenis syndrome (del 17p11.2) SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE SMS; chromosome 17; behavioral phenotype; sleep disturbance; multiple congenital anomaly (MCA); mental retardation syndrome ID CONTIGUOUS-GENE SYNDROME; IN-SITU HYBRIDIZATION; MARIE-TOOTH DISEASE; INTERSTITIAL DELETION; HUMAN HOMOLOG; CHROMOSOME-17; REGION; MAPS; (17)(P11.2P11.2); DEL(17)(P11.2) AB Smith-Magenis syndrome (SMS) is a distinct and clinically recognizable multiple congenital anomaly (MCA) and mental retardation syndrome caused by an interstitial deletion of chromosome 17 p11.2. The phenotype of SMS has been well described and includes: a characteristic pattern of physical features; a hoarse, deep voice; speech delay with or without associated hearing loss; signs of peripheral neuropathy; variable levels of mental retardation; and neurobehavioral problems. Although self-injury and sleep disturbance are major problems in SMS, studies are limited on the behavioral phenotype of SMS. This report reviews the current state of knowledge about SMS and presents new data based on syndrome-specific observations by the authors' longitudinal experience working with SMS, specifically related to the behavioral aspects of SMS. This information should have relevance for parents, clinicians, geneticists, and educators involved in the care of individuals with SMS. (C) 1998 Wiley-Liss, Inc. C1 Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, Washington, DC 20007 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. RP Smith, ACM (reprint author), Natl Human Genome Res Inst, Med Genet Branch, NIH, 10 Center Dr,MSC 1267,Bldg 10,Room 3D53, Bethesda, MD 20892 USA. EM acmsmith@nhgri.nih.gov NR 50 TC 98 Z9 98 U1 0 U2 7 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAR 28 PY 1998 VL 81 IS 2 BP 179 EP 185 DI 10.1002/(SICI)1096-8628(19980328)81:2<179::AID-AJMG10>3.0.CO;2-E PG 7 WC Genetics & Heredity SC Genetics & Heredity GA ZL510 UT WOS:000073440800010 PM 9613859 ER PT J AU Smith, ACM Dykens, E Greenberg, F AF Smith, ACM Dykens, E Greenberg, F TI Sleep disturbance in Smith-Magenis syndrome (del 17 p11.2) SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE SMS; chromosome del 17 p11.2; behavioral phenotype; sleep disturbance; mental retardation; biologic clock; sleep cycle ID CONTIGUOUS-GENE SYNDROME; INTERSTITIAL DELETION; 17P11.2; (17)(P11.2P11.2); ABNORMALITIES; MELATONIN; DISORDERS AB Smith-Magenis syndrome (SMS) is a clinically recognizable multiple congenital anomaly and mental retardation syndrome caused by an interstitial deletion of chromosome 17 p11.2. Although the physical and molecular genetic features of SMS are increasingly well understood, work is more limited on SMS's behavioral phenotype, which includes self-injury, tantrums, and sleep disturbance. This study examines the sleep behaviors of 39 individuals with SMS, ranging in age from 1.6 to 32 years (mean = 10.5). Prominent sleep problems, seen in 65 to 100% of the sample, included difficulties falling asleep, shortened sleep cycles, frequent and prolonged nocturnal awakenings, excessive daytime sleepiness, daytime napping, snoring, and bed-wetting. Medication to facilitate sleep was used by 59% of SMS subjects. Possible etiologic mechanisms of sleep disturbance in SMS are discussed, as are recommended interventions. (C) 1998 Wiley-Liss, Inc. C1 Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, Washington, DC 20007 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. RP Smith, ACM (reprint author), Natl Human Genome Res Inst, Med Genet Branch, NIH, 10 Center Dr,MSC 1267,Bldg 10,Room 3D53, Bethesda, MD 20892 USA. NR 26 TC 91 Z9 91 U1 2 U2 9 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAR 28 PY 1998 VL 81 IS 2 BP 186 EP 191 DI 10.1002/(SICI)1096-8628(19980328)81:2<186::AID-AJMG11>3.0.CO;2-D PG 6 WC Genetics & Heredity SC Genetics & Heredity GA ZL510 UT WOS:000073440800011 PM 9613860 ER PT J AU Tomic-Carruthers, N Gorden, P AF Tomic-Carruthers, N Gorden, P TI Effects of proteasomal inhibitors on the maturation of the insulin proreceptor: An anatomical paradox SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID RECEPTOR ALPHA-SUBUNIT; LYSOSOMAL ASSOCIATION; GROWTH-HORMONE; GLYCOSYLATION; INTERNALIZATION; BIOSYNTHESIS; DEGRADATION; ENDOCYTOSIS; BINDING; CFTR AB Inhibitors of proteasomal functions Carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG132) and Carbobenzoxy-L-isoleucyl-gamma-t-butyl-L-alanyl-L-leucinal (PSI) were found to inhibit the conversion of the Insulin proreceptor to its mature alpha and beta subunits. By contrast no effect of these inhibitors was found on (125)-I insulin binding, internalization and degradation, Since the insulin proreceptor is an integral membrane protein that is compartmentally separated from the cytoplasmic 26S proteasome, the inhibition of the normal biosynthetic processing of the insulin proreceptor presents an anatomical paradox. (C) 1998 Academic Press. C1 NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Tomic-Carruthers, N (reprint author), NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. NR 21 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 27 PY 1998 VL 244 IS 3 BP 728 EP 731 DI 10.1006/bbrc.1998.8333 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZF658 UT WOS:000072919100021 PM 9535733 ER PT J AU Patterton, HG Landel, CC Landsman, D Peterson, CL Simpson, RT AF Patterton, HG Landel, CC Landsman, D Peterson, CL Simpson, RT TI The biochemical and phenotypic characterization of Hho1p, the putative linker histone H1 of Saccharomyces cerevisiae SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HIGHER-ORDER STRUCTURE; NUCLEOSOME CORE PARTICLE; DROSOPHILA-MELANOGASTER; CRYSTAL-STRUCTURE; GLOBULAR DOMAIN; H-1 HISTONES; CHROMATIN CONDENSATION; CAENORHABDITIS-ELEGANS; NUCLEOTIDE-SEQUENCE; HO GENE AB There is currently no published report on the isolation and definitive identification of histone H1 in Saccharomyces cerevisiae. It was, however, recently shown that the yeast HHO1 gene codes for a predicted protein homologous to H1 of higher eukaryotes (Landsman, D. (1996) Trends Biochem. Sci. 21, 287-288; Ushinsky, S. C., Bussey, H., Ahmed, A. A., Wang, Y., Friesen, J., Williams, B. A., and Storms, R. K. (1997) Yeast 13, 151-161), although there is no biochemical evidence that shows that Hho1p is, indeed, yeast histone H1, We showed that purified recombinant Hho1p (rHho1p) has electrophoretic and chromatographic properties similar to linker histones. The protein forms a stable ternary complex with a reconstituted core di-nucleosome in vitro at molar rHho1p:core ratios up to 1. Reconstitution of rHho1p with H1-stripped chromatin confers a kinetic pause at similar to 168 base pairs in the micrococcal nuclease digestion pattern of the chromatin, These results strongly suggest that Hho1p is a bona fide linker histone, We deleted the HHO1 gene and showed that the strain is viable and has no growth or mating defects. Hho1p is not required for telomeric silencing, basal transcriptional repression, or efficient sporulation. Unlike core histone mutations, a hho1 Delta strain does not exhibit a Sin or Spt phenotype. The absence of Hho1p does not lead to a change in the nucleosome repeat length of bulk chromatin nor to differences in the in vivo micrococcal nuclease cleavage sites in individual genes as detected by primer extension mapping. C1 Penn State Univ, Dept Biochem & Mol Biol, Althouse Labs 308, University Pk, PA 16802 USA. Univ Massachusetts, Med Ctr, Program Mol Med, Worcester, MA 01605 USA. Univ Massachusetts, Med Ctr, Dept Biochem & Mol Biol, Worcester, MA 01605 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Patterton, HG (reprint author), Penn State Univ, Dept Biochem & Mol Biol, Althouse Labs 308, University Pk, PA 16802 USA. EM hgp1@psu.edu RI Landsman, David/C-5923-2009; OI Landsman, David/0000-0002-9819-6675; Patterton, Hugh-George/0000-0003-2550-0493 FU NIGMS NIH HHS [1 RO1 GM52399, 1 RO1 GM54096, R01 GM054096] NR 87 TC 101 Z9 103 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 27 PY 1998 VL 273 IS 13 BP 7268 EP 7276 DI 10.1074/jbc.273.13.7268 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZD917 UT WOS:000072738500016 PM 9516420 ER PT J AU Radjendirane, V Joseph, P Lee, YH Kimura, S Klein-Szanto, AJP Gonzalez, FJ Jaiswal, AK AF Radjendirane, V Joseph, P Lee, YH Kimura, S Klein-Szanto, AJP Gonzalez, FJ Jaiswal, AK TI Disruption of the DT diaphorase (NQ01) gene in mice leads to increased menadione toxicity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NAD(P)H-MENADIONE OXIDOREDUCTASE; METABOLIZING-ENZYMES; CDNA SEQUENCE; CANCER; DIOXIN; ANTIOXIDANT; EXPRESSION; CHEMOTHERAPY; POLYMORPHISM; MUTAGENICITY AB NAD(P)H:quinone oxidoreductase 1 (NQO1) is a flavoenzyme that catalyzes two-electron reductive metabolism and detoxification of quinones and their derivatives leading to protection of cells against redox cycling and oxidative stress. To examine the in vivo role of NQO1, a NQO1-null mouse was produced using targeted gene disruption. Mice lacking NQO1 gene expression showed no detectable phenotype and were indistinguishable from wild-type mice. However, NQO1-null mice exhibited increased toxicity when administered menadione compared with wild-type mice. These results establish a role for NQO1 in protection against quinone toxicity. The NQO1-null mice are a model for NQO1 deficiency in humans and can be used to determine the role of this enzyme in sensitivity to toxicity and carcinogenesis. C1 Baylor Coll Med, Dept Pharmacol, Houston, TX 77030 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. Fox Chase Canc Ctr, Dept Pathol, Philadelphia, PA 19111 USA. RP Jaiswal, AK (reprint author), Baylor Coll Med, Dept Pharmacol, 1 Baylor Plaza, Houston, TX 77030 USA. RI Klein-Szanto, Andres/E-6218-2010 FU NIEHS NIH HHS [R01 ES07943] NR 41 TC 181 Z9 187 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 27 PY 1998 VL 273 IS 13 BP 7382 EP 7389 DI 10.1074/jbc.273.13.7382 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZD917 UT WOS:000072738500031 PM 9516435 ER PT J AU Warder, SE Prorok, M Chen, ZG Li, LP Zhu, Y Pedersen, LG Ni, F Castellino, FJ AF Warder, SE Prorok, M Chen, ZG Li, LP Zhu, Y Pedersen, LG Ni, F Castellino, FJ TI The roles of individual gamma-carboxyglutamate residues in the solution structure and cation-dependent properties of conantokin-T SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID METHYL-D-ASPARTATE; CONTAINING PEPTIDES; SECONDARY STRUCTURE; CALCIUM; ACID; ANTAGONIST; CHANNELS; BINDING; VENOMS AB The solution structure of the Ca2+-loaded conantokin-T (con-T), a gamma-carboxyglutamate (Gla)-containing al-residue peptide (NH2-G(1)E gamma gamma Y(5)QKML gamma(10)NLR gamma A(15)EVKKN(20)A-CONH2, gamma = = Gla), has been elucidated by use of distance geometry calculations with experimental distances derived from two-dimensional H-1 NMR spectroscopy. An end-to-end cc-helix was the dominant conformation in solution, similar to that of apo-con-T, except that reorientation of several side chains occurred in the Ca2+-coordinated complex. The most notable examples of this were those of Gla(10) and Gla(14), which were more optimally positioned for complexation with Ca2+. In addition to the stabilization offered to the alpha-helix by Ca2+ binding, hydrophobic clustering of the side chains of Tyr(5), Met(8), Leu(9), and Leu(12), and ionic interactions between Lys(7) and Gla(3)/Gla(10) and between Arg(13) and Gla(14), along with hydrogen bonding between Gln(6) and Gla(10), were among the side chain interactions Likely playing a significant role in maintenance of the alpha-helical conformation. Docking of Ca2+ in the con-T structure was accomplished using genetic algorithm-molecular dynamics simulation approaches. The results showed that one Ca2+ ion is most likely coordinated by four side chain oxygen atoms, two each from Gla(10) and Gla(14). Another bound Ca2+ ion has as its donor sites three oxygen atoms, two from Gla(3) and one from Gln(6). To examine the functional roles of the individual Gla residues, a series of variant peptides have been synthesized with Ala substituted for each Gla residue, and several properties of the resulting variants have been examined. The data obtained demonstrated the importance of Gla(10) and Gla(14) in stabilizing binding of the highest affinity Ca2+ site and in governing the conformational change induced by Ca2+. The critical nature of Gla(3) and Gla(4) in inhibition of the spermine-induced potentiation of the binding of MK-801 to open ion channels of the N-methyl-D-aspartate receptor was established, as well as the role of Gla(4) in stabilizing the apo-con-T alpha-helical conformation. C1 Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA. Natl Res Council Canada, Biotechnol Res Inst, Montreal Joint Ctr Struct Biol, Biomol NMR Lab, Montreal, PQ H4P 2R2, Canada. NIEHS, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. RP Castellino, FJ (reprint author), Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 FU NHLBI NIH HHS [HL-06530, HL-19982] NR 29 TC 26 Z9 26 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 27 PY 1998 VL 273 IS 13 BP 7512 EP 7522 DI 10.1074/jbc.273.13.7512 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZD917 UT WOS:000072738500048 PM 9516452 ER PT J AU Nims, RW Lubet, RA Fox, SD Jones, CR Thomas, PE Reddy, AB Kocarek, TA AF Nims, RW Lubet, RA Fox, SD Jones, CR Thomas, PE Reddy, AB Kocarek, TA TI Comparative pharmacodynamics of CYP2B induction by DDT, DDE, and DDD in male rat liver and cultured rat hepatocytes SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A LA English DT Article ID CYTOCHROME-P450-2B INDUCTION; F344/NCR RAT; P450 2B; METABOLISM; 5-ETHYL-5-PHENYLHYDANTOIN; MICROSOMES; SUBFAMILY; INDUCERS; EXPOSURE; ISOZYMES AB In this study the pharmacodynamics were characterized of rat hepatic cytochrome P-450 2B (CYP2B) induction by the pesticide DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] and its metabolites DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene], which is bioretained, and DDD [1,1-dichloro-2,2-bis(p-chlorophenyl)ethane] which is metabolized further and therefore less prone to bioaccumulate. DDT, DDE, and DDD were each found to be pure phenobarbital-type cytochrome P-450 inducers in the male F344/NCr rat, causing induction of hepatic CYP2B and CYP3A, but not CYP1A. The ED50 values for CYP2B induction (benzyloxyresorufin O-dealkylation) by DDT, DDE, and DDD were, respectively, 103, 88, and greater than or equal to 620 ppm in diet (14 d of exposure). The efficacies (E-max values) for induction of benzyloxyresorufin O-dealkylation by DDT, DDE, and DDD were 24-, 22-, and greater than or equal to 21-fold respectively, compared to control values. The potencies of the three congeners for CYP2B induction appeared also to be similar, with EC50 values (based on total serum DDT equivalents) of 1.5, 1.8, and greater than or equal to 0.51 mu M, respectively. The EC50 values based on DDT equivalents in hepatic tissue were 15, 16, and greater than or equal to 5.9 mu mol/kg liver tissue, respectively. In primary cultures of adult rat hepatocytes, DDT, DDE, and DDD each displayed ability to induce total cellular RNA coding for CYP2B (ED50 values of 0.98, 0.83, and greater than or equal to 2.7 mu M, respectively). These results suggest that DDT, DDE, and DDD each possess a high degree of intrinsic CYP2B-inducing ability for rat liver, despite marked differences in bioretention among the congeners. C1 NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. NCI, Div Canc Prevent & Control, Chemoprevent Branch, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Chem Synth & Anal Lab, Frederick, MD USA. NIA, Neurosci Lab, Bethesda, MD 20892 USA. Rutgers State Univ, Coll Pharm, Dept Biol Chem, Piscataway, NJ USA. Wayne State Univ, Inst Chem Toxicol, Detroit, MI 48201 USA. RP Nims, RW (reprint author), BioServ Inc, 9900 Blackwell Rd, Rockville, MD 20850 USA. FU NHLBI NIH HHS [HL50710]; NIEHS NIH HHS [ES06639] NR 40 TC 49 Z9 50 U1 2 U2 5 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0098-4108 J9 J TOXICOL ENV HEAL A JI J. TOXICOL. ENV. HEALTH PT A PD MAR 27 PY 1998 VL 53 IS 6 BP 455 EP 477 PG 23 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA ZE291 UT WOS:000072777300003 PM 9537282 ER PT J AU Tess, BH Rodrigues, LC Newell, ML Dunn, DT Lago, TDG AF Tess, BH Rodrigues, LC Newell, ML Dunn, DT Lago, TDG CA Sao Paulo Collaborative Study Vertical Transmi TI Breastfeeding, genetic, obstetric and other risk factors associated with mother-to-child transmission of HIV-1 in Sao Paulo State, Brazil SO AIDS LA English DT Article DE risk factors; vertical HIV-1 transmission; breastfeeding; Latin America; obstetrics; paediatrics; epidemiology ID HUMAN-IMMUNODEFICIENCY-VIRUS; ZIDOVUDINE TREATMENT; PERINATAL TRANSMISSION; VERTICAL TRANSMISSION; TYPE-1 INFECTION; VIRAL LOAD; PREGNANCY; MEMBRANES; BEHAVIOR; DURATION AB Objectives: To evaluate the effect of maternal, obstetric, neonatal and post-natal factors on the risk of vertical transmission of HIV-1. Design: Multicentre retrospective cohort study. Setting: Obstetric and paediatric clinics in four cities in Sao Paulo State, Brazil. Main outcome: Child's HIV-1 infection status. Methods: Data were collected by standardized record abstraction and interview on 553 children born to women identified as HIV-1-infected before or at delivery. Paediatric infection was determined by immunoglobulin G anti-HIV-1 tests at age 18 months or by AIDS diagnosis at any age. Multivariate logistic regression was used to assess the effect of potential risk factors on vertical transmission of HIV-1. Results: HIV-1 infection status was determined for 434 children (follow-up rate of 78%); 69 were classified as HIV-1-infected [transmission risk, 16%; 95% confidence interval (CI), 13-20%]. In multivariate analysis, advanced maternal HIV-1 disease [odds ratio (OR), 4.5; 95% CI, 2.1-9.5], ever breastfed (OR, 2.2; 95% CI, 1.2-4.2), child's negative Rhesus blood group (OR, 2.5; 95% CI, 1.2-5.5), third trimester amniocentesis (OR, 4.1; 95% CI, 1.2-13.5) and black racial group (OR, 0.3; 95% CI, 0.1-0.9) were independently and significantly associated with mother-to-child transmission of HIV-1. Transmission was increased marginally with prematurity, more than 10 lifetime sexual partners and prolonged duration of membrane rupture. No association was found between child's HIV-1 infection and mode of delivery or serological evidence of syphilis during pregnancy. Conclusion: These findings support the importance of severity of maternal HIV-1 disease in the risk of vertical transmission of HIV-1, indicate measures to reduce transmission by avoiding amniocentesis and breastfeeding and suggest that race and Rhesus blood type may be markers for genetic susceptibility to infection. (C) 1998 Rapid Science Ltd. C1 London Sch Hyg & Trop Med, London WC1, England. Inst Child Hlth, London, England. Dept Hlth State Sao Paulo, Inst Hlth, Sao Paulo, Brazil. RP Tess, BH (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6130 Execut Blvd,EPN-434, Rockville, MD 20852 USA. OI Newell, Marie-Louise/0000-0002-1074-7699 NR 39 TC 92 Z9 108 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0269-9370 J9 AIDS JI Aids PD MAR 26 PY 1998 VL 12 IS 5 BP 513 EP 520 DI 10.1097/00002030-199805000-00013 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA YY998 UT WOS:000072209900013 PM 9543450 ER PT J AU Granja, R Strakhova, M Knauer, CS Skolnick, P AF Granja, R Strakhova, M Knauer, CS Skolnick, P TI Anomalous rectifying properties of 'diazepam-insensitive' GABA(A) receptors SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE GABA(A) receptor; rectification; point mutation; alpha subunit ID CEREBELLAR GRANULE CELLS; BENZODIAZEPINE RECEPTORS; A RECEPTORS; STRUCTURAL DETERMINANTS; SINGLE HISTIDINE; ALPHA-4 SUBUNIT; LIGAND-BINDING; PHARMACOLOGY; CLONING; STOICHIOMETRY AB Studies using recombinant systems indicate that 'diazepam-insensitive' GABA(A) receptors in the central nervous system contain alpha 4 and alpha 6 subunits while 'diazepam-sensitive' GABA(A) receptors contain alpha 1, alpha 2, alpha 3 and alpha 5 subunits. Both native and recombinant diazepam-sensitive GABA(A) receptors typically exhibit large, outwardly rectifying currents. For example, in patch clamp studies, Human Embryonic Kidney (HEK) 293 cells transfected with cDNAs encoding alpha 1 beta 2 gamma 2 subunits exhibit a rectification ratio (I+60 mV/I-60 mV) of 1.95 +/- 0.21. However, anomalous rectification was observed in recombinant diazepam-insensitive GABA(A) receptors composed of either alpha 4 beta 2 gamma 2 (rectification ratio, 0.74 +/- 0.09) or alpha 6 beta 2 gamma 2 (rectification ratio, 0.67 +/- 0.11) subunits. Based on sequence differences between diazepam-sensitive and -insensitive GABA(A) receptor alpha subunits in the vicinity of the putative channel lining, a point mutation was introduced at His(273) on the alpha 4 subunit. The rectification ratio in cells expressing a mutated alpha 4(Asn(273))beta 2 gamma 2 receptor increased to 1.92+/-0.17. Moreover, mutation of the homologous residue in the alpha 1 subunit to histidine reduced the rectification ratio of alpha 1(His(274))beta 2 gamma 2 to 1.02 +/- 0.12. The affinities of benzodiazepine site ligands at diazepam-sensitive and -insensitive GABA(A) receptors were unaffected by these mutations. Thus, the electrophysiological properties of diazepam-sensitive and -insensitive GABA, receptors may be as divergent as their pharmacological characteristics. (C) 1998 Elsevier Science B.V. C1 NIDDK, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Skolnick, P (reprint author), Lilly Corp Ctr, Lilly Res Labs, Bldg 48,Drop Code 01510, Indianapolis, IN 46285 USA. EM skol-nick_phil@lilly.com NR 43 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD MAR 26 PY 1998 VL 345 IS 3 BP 315 EP 321 DI 10.1016/S0014-2999(98)00025-9 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZK110 UT WOS:000073285900012 PM 9592032 ER PT J AU Dimmock, JR Kandepu, NM Hetherington, M Quail, JW Pugazhenthi, U Sudom, AM Chamankhah, M Rose, P Pass, E Allen, TM Halleran, S Szydlowski, J Mutus, B Tannous, M Manavathu, EK Myers, TG De Clercq, E Balzarini, J AF Dimmock, JR Kandepu, NM Hetherington, M Quail, JW Pugazhenthi, U Sudom, AM Chamankhah, M Rose, P Pass, E Allen, TM Halleran, S Szydlowski, J Mutus, B Tannous, M Manavathu, EK Myers, TG De Clercq, E Balzarini, J TI Cytotoxic activities of Mannich bases of chalcones and related compounds SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DEVELOPMENT PROGRAM; DRUG DEVELOPMENT; INHIBITION; MECHANISM; CARCINOGENESIS; PROLIFERATION; KETONES; GROWTH; ASSAY AB Various Mannich bases of chalcones and related compounds displayed significant cytotoxicity toward murine P388 and L1210 leukemia cells as well as a number of human tumor cell lines. The most promising lead molecule was 21 that had the highest activity toward L1210 and human tumor cells. In addition, 21 exerted preferential toxicity to human tumor lines compared to transformed human T-lymphocytes. Other compounds of interest were 38, with a huge differential in cytotoxicity between P388 and L1210 cells, and 42, with a high therapeutic index when cytotoxicity to P388 cells and Molt 4/C8 T-lymphocytes were compared. In general, the Mannich bases were more cytotoxic than the corresponding chalcones toward L1210 but not P388 cells. A ClusCor analysis of the data obtained from the in vitro human tumor screen revealed that the mode of action of certain groups of compounds was similar. For some groups of compounds, cytotoxicity was correlated with the sigma, pi, or molar refractivity constants in the aryl ring attached to the olefinic group. In addition, the IC(50) values in all three screens correlated with the redox potentials of a number of Mannich bases. X-ray crystallography and molecular modeling of representative compounds revealed various structural features which were considered to contribute to cytotoxicity. While a representative compound 15 was stable and unreactive toward glutathione (GSH) in buffer, the Mannich bases 15, 18, and 21 reacted with GSH in the presence of the pi isozyme of glutathione S-transferase, suggesting that thiol alkylation may be one mechanism by which cytotoxicity was exerted in vitro. Representative compounds were shown to be nonmutagenic in an intrachromosomal recombination assay in yeast, devoid of antimicrobial properties and possessing anticonvulsant and neurotoxic properties. Thus Mannich bases of chalcones represent a new group of cytotoxic agents of which 21 in particular serves as an useful prototypic molecule. C1 Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK S7N 5C9, Canada. Univ Saskatchewan, Dept Chem, Saskatoon, SK S7N 5C9, Canada. Univ Saskatchewan, Dept Microbiol, Saskatoon, SK S7N 5C9, Canada. Inst Plant Biotechnol, Saskatoon, SK S7N 0W9, Canada. Univ Alberta, Dept Pharmacol, Edmonton, AB T6G 2H7, Canada. Univ Windsor, Dept Chem & Biochem, Windsor, ON N9B 3P4, Canada. Wayne State Univ, Dept Internal Med, Detroit, MI 48201 USA. NCI, NIH, Bethesda, MD 20892 USA. Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium. RP Dimmock, JR (reprint author), Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK S7N 5C9, Canada. NR 53 TC 128 Z9 130 U1 2 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 26 PY 1998 VL 41 IS 7 BP 1014 EP 1026 DI 10.1021/jm970432t PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA ZE998 UT WOS:000072852600003 PM 9544201 ER PT J AU Ucar, H Van derpoorten, K Cacciaguerra, S Spampinato, S Stables, JP Depovere, P Isa, M Masereel, B Delarge, J Poupaert, JH AF Ucar, H Van derpoorten, K Cacciaguerra, S Spampinato, S Stables, JP Depovere, P Isa, M Masereel, B Delarge, J Poupaert, JH TI Synthesis and anticonvulsant activity of 2(3H)-benzoxazolone and 2(3H)-benzothiazolone derivatives SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ANTIEPILEPTIC DRUG DEVELOPMENT; RECEPTORS; LIGANDS; RATS; FELBAMATE; 5-HT1A; MICE AB A series of 2(3H)-benzoxazolone and 2(3H)-benzothiazolone derivatives were synthesized and evaluated for anticonvulsant activity. The compounds were assayed, intraperitoneally in mice and per os in rats, against seizures induced by maximal electroshock (MES) and pentylenetetrazole (scMet). Neurologic deficit was evaluated by the rotarod test. The compounds were prepared to determine the relationship between the 2(3H)-benzoxazolone and 2(3H)-benzothiazolone derivatives' structures and anticonvulsant activity. Several of these compounds showed significant anticonvulsant activity. Compounds 43 and 45 were the most active of the series against MES-induced seizures with ED50 values of 8.7 and 7.6 mg/kg, respectively. Compound 45 displayed good protection against MES-induced seizures and low toxicity in rats with an oral ED50 Of 18.6 mg/kg and a protective index (PI = TD50/ED50) Of <26.9. In vitro receptor binding studies revealed that compounds 43 and 45 bind to al receptors with nanomolar affinities. C1 Univ Louvain, Sch Pharm, Med Chem Lab, B-1200 Brussels, Belgium. Univ Bologna, Dept Pharmacol, I-40126 Bologna, Italy. NINDS, Antiepilept Drug Dev Program, NIH, Bethesda, MD 20892 USA. Univ Liege, Med Chem Lab, B-4000 Liege, Belgium. RP Ucar, H (reprint author), Univ Louvain, Sch Pharm, Med Chem Lab, Ave Emmanuel Mournier 73,UCL 7340, B-1200 Brussels, Belgium. NR 43 TC 83 Z9 87 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 26 PY 1998 VL 41 IS 7 BP 1138 EP 1145 DI 10.1021/jm970682+ PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA ZE998 UT WOS:000072852600015 PM 9544213 ER PT J AU Xia, Y Yang, ZY Xia, P Bastow, KF Tachibana, Y Kuo, SC Hamel, E Hackl, T Lee, KH AF Xia, Y Yang, ZY Xia, P Bastow, KF Tachibana, Y Kuo, SC Hamel, E Hackl, T Lee, KH TI Antitumor agents. 181. Synthesis and biological evaluation of 6,7,2 ',3 ',4 '-substituted-1,2,3,4-tetrahydro-2-phenyl-4-quinolones as a new class of antimitotic antitumor agents SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID TUBULIN POLYMERIZATION; COLCHICINE; DERIVATIVES; ANALOGS; 2-PHENYL-4-QUINOLONES; COMBRETASTATIN-A-4; CYTOTOXICITY; INHIBITION; MECHANISM; FLAVONOLS AB A novel series of 6,7,2',3',4'-substituted-1,2,3,4-tetrahydro-2-phenyl-4-quinolones were synthesized and evaluated for interactions with tubulin and for cytotoxic activity against a panel of human tumor cell lines, including ileocecal carcinoma (HCT-8), breast cancer (MCF-7), lung carcinoma (A-549), epidermoid carcinoma of the nasopharynx (KB), renal cancer (CAKI-1), and melanoma cancer (SKMEL-2). Most compounds (18, 20, 22-27) showed potent cytotoxic and antitubulin effects. The most active compounds (23, 26, 27) demonstrated strong cytotoxic effects with ED50 values in the nanomolar or subnanomolar range in almost all tumor cell lines. Three active racemates (20, 22, 25) were separated into the enantiomers, and generally, the optically pure (-)-isomers (20a, 22a, 25a) exhibited greater biological activity than the racemates or (+)-isomers. Cytotoxicity and antitubulin activity were closely correlated, with the most active compounds (23, 26, 27) having effects comparable to those of colchicine, podophyllotoxin, and combretastatin A-4. C1 Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Nat Prod Lab, Chapel Hill, NC 27599 USA. China Med Coll, Taichung, Taiwan. NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Lee, KH (reprint author), Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Nat Prod Lab, Chapel Hill, NC 27599 USA. FU NCI NIH HHS [CA-17625] NR 32 TC 188 Z9 191 U1 1 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 26 PY 1998 VL 41 IS 7 BP 1155 EP 1162 DI 10.1021/jm9707479 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA ZE998 UT WOS:000072852600017 PM 9544215 ER PT J AU An, WG Kanekal, M Simon, MC Maltepe, E Blagosklonny, MV Neckers, LM AF An, WG Kanekal, M Simon, MC Maltepe, E Blagosklonny, MV Neckers, LM TI Stabilization of wild-type p53 by hypoxia-inducible factor 1 alpha SO NATURE LA English DT Article ID DNA-BINDING ACTIVITY; GROWTH-FACTOR GENE; FACTOR-I; TRANSCRIPTION FACTOR; ERYTHROPOIETIN GENE; SIGNAL-TRANSDUCTION; ACTIVATION; EXPRESSION; RECEPTOR; PROTEIN AB Although hypoxia (lack of oxygen in body tissues) is perhaps the most physiological inducer of the wild-type p53 gene(1), the mechanism of this induction is unknown. Cells may detect low oxygen levels through a haem-containing sensor protein(2), The hypoxic state can be mimicked by using cobalt chloride and the iron chelator desferrioxamine(2-5): like hypoxia, cobalt chloride and desferrioxamine activate hypoxia-inducible factor 1 alpha (HIF-1 alpha) (ref. 6), which stimulates the transcription of several genes that are associated with hypoxia(6-9). Here we show that these treatments induce accumulation of wild-type p53 through HIF-1 alpha-dependent stabilization of p53 protein. Induction of p53 does not occur in either a mutant hepatoma cell line that is unable to induce HIF-1 alpha (ref. 10) or embryonic stem cells derived from mice lacking HIF-1 beta (ref. 11). HIF-1 alpha is found in p53 immunoprecipitates from II MCF7 cells that express wild-type p53 and are either hypoxic or have been exposed to desferrioxamine. Similarly, anti-haemagglutinin immunoprecipitates from lysates of normoxic PC3M cells that had been co-transfected with haemagglutinin-tagged HIF-1 alpha and wild-type p53 also contain p53. Transfection of normoxic MCF7 cells with HIF-1 alpha. stimulates a co-transfected p53-dependent reporter plasmid and increases the amount of endogenous p53. Our results suggest that hypoxic induction of transcriptionally active wild-type p53 is achieved as a result of the stabilization of p53 by its association with HIF-1 alpha. C1 NCI, Med Branch, NIH, Rockville, MD 20850 USA. NCI, Dept Cell & Canc Biol, Med Branch, NIH, Bethesda, MD 20892 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Univ Chicago, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA. Univ Chicago, Howard Hughes Med Inst, Dept Pathol, Chicago, IL 60637 USA. RP Neckers, LM (reprint author), NCI, Med Branch, NIH, Key W Facil,9610 Med Ctr Dr,Room 300, Rockville, MD 20850 USA. EM len@helix.nih.gov NR 23 TC 609 Z9 638 U1 2 U2 30 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD MAR 26 PY 1998 VL 392 IS 6674 BP 405 EP 408 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZD694 UT WOS:000072713600056 PM 9537326 ER PT J AU Monzon, J Liu, L Brill, H Goldstein, AM Tucker, MA From, L McLaughlin, J Hogg, D Lassam, NJ AF Monzon, J Liu, L Brill, H Goldstein, AM Tucker, MA From, L McLaughlin, J Hogg, D Lassam, NJ TI CDKN2A mutations in multiple primary melanomas SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID FAMILIAL MELANOMA; MALIGNANT-MELANOMA; GERMLINE MUTATIONS; CANCER; KINDREDS; RISK; RETINOBLASTOMA; GENE AB Background Germ-line mutations in the CDKN2A tumor-suppressor gene (also known as p16, p16(INK4a), and MTS1) have been linked to the development of melanoma in some families with inherited melanoma. Whether mutations in CDKN2A confer a predisposition to sporadic (nonfamilial) melanoma is not known. In some patients with sporadic melanoma, one or more additional primary lesions develop, suggesting that some of these patients have an un derlying genetic susceptibility to the cancer. We hypothesized that this predisposition might be due to germ-line CDKN2A mutations. Methods We used the polymerase chain reaction, single-strand conformation polymorphism analysis, and direct DNA sequencing to identify germ-line mutations in the CDKN2A gene in patients with multiple primary melanomas who did not have family histories of the disease. A quantitative yeast two-hybrid assay was used to evaluate the functional importance of the CDKN2A variants. Results Of 33 patients with multiple primary melanomas, 5 (15 percent; 95 percent confidence interval, 4 percent to 27 percent) had germ-line CDKN2A mutations. These included a 24-bp insertion at the 5' end of the coding sequence, three missense mutations (Arg24Pro, Met53lle, and Ser56lle), and a 2-bp deletion at position 307 to 308 (resulting in a truncated CDKN2A protein). In three families, CDKN2A mutations identical to those in the probands were found in other family members. In two families with mutations, we uncovered previously unknown evidence of family histories of melanoma. Conclusions Some patients with multiple primary melanomas but without family histories of the disease have germ-line mutations of the CDKN2A gene. The presence of multiple primary melanomas may signal a genetic susceptibility to melanoma not only in the index patient but also in family members, who may benefit from melanoma-surveillance programs. (C) 1998, Massachusetts Medical Society. C1 Toronto Sunnybrook Reg Canc Ctr, Div Med Oncol, Toronto, ON M4N 3M5, Canada. Univ Toronto, Inst Med Sci, Toronto, ON, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. Univ Toronto, Dept Dermatol, Toronto, ON, Canada. Univ Toronto, Dept Prevent Med & Biostat, Toronto, ON, Canada. NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. RP Lassam, NJ (reprint author), Toronto Sunnybrook Reg Canc Ctr, Div Med Oncol, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada. RI McLaughlin, John/E-4577-2013; Tucker, Margaret/B-4297-2015 NR 36 TC 174 Z9 181 U1 0 U2 3 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 26 PY 1998 VL 338 IS 13 BP 879 EP 887 DI 10.1056/NEJM199803263381305 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA ZD284 UT WOS:000072669800005 PM 9516223 ER PT J AU Jain, R Avramovitch, B Cohen, LA AF Jain, R Avramovitch, B Cohen, LA TI Synthesis of ring-halogenated histidines and histamines SO TETRAHEDRON LA English DT Article ID IODINATED COMPOUNDS; ANALOGS AB Series of ring-halogenated histidines and histamines have been synthesized from the suitably protected parent bioimidazoles. The 5-X and 2,5-X-2-derivatives are obtained by direct electrophilic halogenation while 2-X derivatives (X = Br and I) are prepared by regiospecific electrophilic dehalogenation at C-5. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Jain, R (reprint author), Natl Inst Pharmaceut Educ & Res, Dept Med Chem, Sector 67, SAS Nagar Mohali 160062, Punjab, India. NR 21 TC 21 Z9 21 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD MAR 26 PY 1998 VL 54 IS 13 BP 3235 EP 3242 DI 10.1016/S0040-4020(98)00068-4 PG 8 WC Chemistry, Organic SC Chemistry GA ZA466 UT WOS:000072366100016 ER PT J AU Siddiqui, MA Driscoll, JS Marquez, VE AF Siddiqui, MA Driscoll, JS Marquez, VE TI A new synthetic approach to the clinically useful, anti-HIV-active nucleoside, 9-(2,3-dideoxy-2-fluoro-beta-D-threo-pentofuranosyl)adenine (beta-FddA). Introduction of a 2 '-beta-fluoro substituent via inversion of a readily obtainable 2 '-alpha-fluoro isomer. SO TETRAHEDRON LETTERS LA English DT Article ID DAST AB A convenient route to the anti-HIV active compound, 9-(2,3-dideoxy-2-fluoro-beta-D-threo-pentofuranosyl)adenine (1, beta-FddA) started with the facile introduction of fluorine at C2' from the alpha-side of protected 9-(beta-D-arabinofuranosyl)adenine (ara-A). Inversion of the stereochemistry at C2' was accomplished via a stable vinyl intermediate (6), which underwent stereoselective reduction of the double bond to give the desired 2'-F-threo isomer with the opposite beta-fluoro stereochemistry. Published by Elsevier Science Ltd. C1 NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Marquez, VE (reprint author), NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 15 TC 13 Z9 13 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD MAR 26 PY 1998 VL 39 IS 13 BP 1657 EP 1660 DI 10.1016/S0040-4039(98)00014-8 PG 4 WC Chemistry, Organic SC Chemistry GA ZA465 UT WOS:000072366000003 ER PT J AU Andersen, RE Crespo, CJ Bartlett, SJ Cheskin, LJ Pratt, M AF Andersen, RE Crespo, CJ Bartlett, SJ Cheskin, LJ Pratt, M TI Relationship of physical activity and television watching with body weight and level of fatness among children - Results from the Third National Health and Nutrition Examination Survey SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CHILDHOOD WEIGHT; US ADULTS; ADOLESCENTS; OVERWEIGHT; OBESITY; EXERCISE; PREVALENCE; MORTALITY; STATEMENT; MORBIDITY AB Context.-Physical inactivity contributes to weight gain in adults, but whether this relationship is true for children of different ethnic groups is not well established, Objective.-To assess participation in vigorous activity and television watching habits and their relationship to body weight and fatness in US children, Design.-Nationally representative cross-sectional survey with an in-person interview and medical examination, Setting and Participants.-Between 1988 and 1994, 4063 children aged 8 through 16 years were examined as part of the National Health and Nutrition Examination Survey III, Mexican Americans and non-Hispanic blacks were oversampled to produce reliable estimates for these groups, Main Outcome Measures.-Episodes of weekly vigorous activity and daily hours of television watched, and their relationship to body mass index and body fatness. Results.-Eighty percent of US children reported performing 3 or more bouts of vigorous activity each week, This rate was lower in non-Hispanic black and Mexican American girls (69% and 73%, respectively). Twenty percent of US children participated in 2 or fewer bouts of vigorous activity per week, and the rate was higher in girls (26%) than in boys (17%), Overall, 26% of US children watched 4 or more hours of television per day and 67% watched at least 2 hours per day, Non-Hispanic black children had the highest rates of watching 4 or more hours of television per day (42%), Boys and girls who watch 4 or more hours of television each day had greater body fat (P<.001) and had a greater body mass index (P<.001) than those who watched less than 2 hours per day, Conclusions.-Many US children watch a great deal of television and are inadequately vigorously active. Vigorous activity levels are lowest among girls, non-Hispanic blacks, and Mexican Americans, Intervention strategies to promote lifelong physical activity among US children are needed to stem the adverse health consequences of inactivity. C1 Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Div Gastroenterol, Baltimore, MD 21224 USA. NHLBI, Dept Hlth & Fitness, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Phys Act & Hlth Branch, Atlanta, GA USA. RP Andersen, RE (reprint author), Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, 333 Cassell Dr,Suite 1640, Baltimore, MD 21224 USA. OI Bartlett, Susan/0000-0001-9755-2490 NR 43 TC 747 Z9 769 U1 9 U2 77 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 25 PY 1998 VL 279 IS 12 BP 938 EP 942 DI 10.1001/jama.279.12.938 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA ZC304 UT WOS:000072563600034 PM 9544768 ER PT J AU Korzekwa, KR Krishnamachary, N Shou, M Ogai, A Parise, RA Rettie, AE Gonzalez, FJ Tracy, TS AF Korzekwa, KR Krishnamachary, N Shou, M Ogai, A Parise, RA Rettie, AE Gonzalez, FJ Tracy, TS TI Evaluation of atypical cytochrome P450 kinetics with two-substrate models: Evidence that multiple substrates can simultaneously bind to cytochrome P450 active sites SO BIOCHEMISTRY LA English DT Article ID CO BINDING; ENDOPLASMIC-RETICULUM; ENZYMES; RABBIT; EXPRESSION; ACTIVATION; DAPSONE; FORM; 2C9 AB Some cytochrome P450 catalyzed reactions show atypical kinetics, and these kinetic processes can be grouped into five categories: activation, autoactivation, partial inhibition, substrate inhibition, and biphasic saturation curves. A two-site model in which the enzyme can bind two substrate molecules simultaneously is presented which can be used to describe all of these observed kinetic properties. Sigmoidal kinetic characteristics were observed for carbamazepine metabolism by CYP3A4 and naphthalene metabolism by CYPs 2B6, 2C8, 2C9, and 3A5 as well as dapsone metabolism by CYP2C9. Naphthalene metabolism by CYP3A4 and naproxen metabolism by CYP2C9 demonstrated nonhyperbolic enzyme kinetics suggestive of a low K-m, low V-max component for the first substrate molecule and a high K-m, high V-max component for the second substrate molecule. 7,8-Benzoflavone activation of phenanthrene metabolism by CYP3A4 and dapsone activation of flurbiprofen and naproxen metabolism by CYP2C9 were also observed. Furthermore, partial inhibition of 7,8-benzoflavone metabolism by phenanthrene was observed, These results demonstrate that various P450 isoforms may exhibit atypical enzyme kinetics depending on the substrate(s) employed and that these results may be explained by a model which includes simultaneous binding of two substrate molecules in the active site. C1 Univ Pittsburgh, Ctr Clin Pharmacol, Pittsburgh, PA 15217 USA. Merck Sharp & Dohme Res Labs, Dept Drug Metab, W Point, PA 19486 USA. Univ Washington, Dept Med Chem, Seattle, WA 98195 USA. NCI, NIH, Lab Metab, Bethesda, MD 20892 USA. W Virginia Univ, Sch Pharm, Dept Basic Pharmaceut Sci, Morgantown, WV 26506 USA. RP Korzekwa, KR (reprint author), Univ Pittsburgh, Med Ctr, Ctr Clin Pharmacol, 623 Scaife Hall, Pittsburgh, PA 15213 USA. FU NIDDK NIH HHS [N01-DK-6-2274]; NIGMS NIH HHS [GM32165] NR 35 TC 395 Z9 401 U1 4 U2 19 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 24 PY 1998 VL 37 IS 12 BP 4137 EP 4147 DI 10.1021/bi9715627 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZF633 UT WOS:000072916600015 PM 9521735 ER PT J AU Virtamo, J Rapola, JM Ripatti, S Heinonen, OP Taylor, PR Albanes, D Huttunen, JK AF Virtamo, J Rapola, JM Ripatti, S Heinonen, OP Taylor, PR Albanes, D Huttunen, JK TI Effect of vitamin E and beta carotene on the incidence of primary nonfatal myocardial infarction and fatal coronary heart disease SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; CARDIOVASCULAR-DISEASE; ALPHA-TOCOPHEROL; ANTIOXIDANT VITAMINS; CONTROLLED TRIAL; E CONSUMPTION; OXIDATION; LDL; ATHEROSCLEROSIS; SUPPLEMENTATION AB Background: Oxidized low-density lipoprotein is involved in the pathogenesis of atherosclerosis. Ln epidemiological studies antioxidants have been inversely related with coronary heart disease. Findings from controlled trials are inconclusive. Methods: We studied the primary preventive effect of vitamin E (alpha tocopherol) and beta carotene supplementation on major coronary events in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a controlled trial undertaken primarily to examine the effects of these agents on cancer. A total of 27 271 Finnish male smokers aged 50 to 69 years with no history of myocardial infarction were randomly assigned to receive vitamin E (50 mg), beta carotene (20 mg), both agents, or placebo daily for 5 to 8 years (median, 6.1 years). The end point was the first major coronary event, either nonfatal myocardial infarction (surviving at least 28 days; n=1204) or fatal coronary heart disease (n=907). Results: The incidence of primary major coronary events decreased 4% (95% confidence interval, -12% to 4%) among recipients of vitamin E and increased 1% (95% confidence interval, -7% to 10%) among recipients of beta carotene compared with the respective nonrecipients. Neither agent affected the incidence of nonfatal myocardial infarction. Supplementation with vitamin E decreased the incidence of fatal coronary heart disease by 8% (95% confidence interval, -19% to 5%), but beta carotene had no effect on this end point. Conclusions: Supplementation with a small dose of vitamin E has only marginal effect on the incidence of fatal coronary heart disease in male smokers with no history of myocardial infarction, but no influence on nonfatal myocardial infarction. Supplementation with beta carotene has no primary preventive effect on major coronary events. C1 Natl Publ Hlth Inst, FIN-00300 Helsinki, Finland. Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. NCI, Bethesda, MD 20892 USA. RP Virtamo, J (reprint author), Natl Publ Hlth Inst, Mannerheimintie 166, FIN-00300 Helsinki, Finland. EM jarmo.virtamo@ktl.fi RI Albanes, Demetrius/B-9749-2015; Ripatti, Samuli/H-9446-2014 OI Ripatti, Samuli/0000-0002-0504-1202 FU NCI NIH HHS [N01-CN-45165] NR 30 TC 179 Z9 187 U1 0 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 23 PY 1998 VL 158 IS 6 BP 668 EP 675 DI 10.1001/archinte.158.6.668 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA ZC306 UT WOS:000072563900015 PM 9521232 ER PT J AU Scortegagna, M Galdzicki, Z Rapoport, SI Hanbauer, I AF Scortegagna, M Galdzicki, Z Rapoport, SI Hanbauer, I TI In cortical cultures of trisomy 16 mouse brain the upregulated metallothionein-I/II fails to respond to H2O2 exposure or glutamate receptor stimulation SO BRAIN RESEARCH LA English DT Article DE trisomy 16 mouse; conical primary culture; oxidative stress; Western blot analysis; metallothionein I/II; hydrogen peroxide; glutamate receptor stimulation ID SUPEROXIDE-DISMUTASE; DOWNS-SYNDROME; GLUTATHIONE-PEROXIDASE; MAJOR COMPONENT; NEURONS; DISEASE; INDUCTION; ELEMENTS; RADICALS; GENES AB To assess whether a defective oxidative defense may contribute to Down's syndrome, we studied the regulation of the metallothionein(MT)-I/II isoforms in primary cultures of cerebral cortex from fetal trisomy 16 mice and their euploid littermates. Western blot analysis showed that MT-I/II was upregulated and the protein carbonyl content was higher in trisomy 16 compared with euploid cultures. Addition of N-acetyl-L-cysteine to the culture medium reduced the increment of MT-I/II in trisomy 16 cortical cells. In euploid, but not trisomic cortical cultures, kainic acid, trans-(+/-)-ACPD, or H2O2 exposure elicited a dose-dependent increase of the MT-I/II immunoblots. In trisomic cells, the MT-I/II immunoblot densities were not increased beyond their elevated basal levels. In contrast, 25 mu M Pb induced MT-I/II, to a similar extent, in cortical cultures from euploid and trisomy 16 mice. This suggests that the antioxidant-but not the metal-response element of the MT-I/II promoter was altered by increased oxidative stress. Our data suggest that, in the trisomy 16 mouse, the effects of increased production of reactive oxygen species, due to the increased SOD-I, GluR5, or amyloid precursor protein gene dosage, is exacerbated by an insufficient or missing antioxidant response. (C) 1998 Elsevier Science B.V. C1 NHLBI, Lab Mol Immunol, Bethesda, MD 20892 USA. NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Hanbauer, I (reprint author), NHLBI, Lab Mol Immunol, Bldg 10,Room 7N-312, Bethesda, MD 20892 USA. NR 40 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 23 PY 1998 VL 787 IS 2 BP 292 EP 298 DI 10.1016/S0006-8993(97)01501-1 PG 7 WC Neurosciences SC Neurosciences & Neurology GA ZK558 UT WOS:000073337100014 PM 9518655 ER PT J AU Velayutham, M Varghese, B Subramanian, S AF Velayutham, M Varghese, B Subramanian, S TI Magneto-structural correlation studies of a ferromagnetically coupled dinuclear vanadium(IV) complex. Single-crystal EPR study SO INORGANIC CHEMISTRY LA English DT Article ID AGENT BIS(MALTOLATO)OXOVANADIUM(IV) BMOV; TRANSITION-METAL; SPECTRA; LIGAND; DIMERS AB The dimer potassium dioxo(citrato)vanadate(IV)-6-water, K-4{VO[O2CCH2C(O)(CO2)CH2CO2]}(2) . 6H(2)O, was prepared by the reaction of citric acid and metavanadate in a neutral solution. The complex crystallizes in the space group P (1) over bar with unit cell parameters a = 8.474(5) Angstrom, b = 8.902(7) Angstrom, c = 9.596(9) Angstrom, alpha = 71.50(6)degrees, beta = 70.81(9)degrees, gamma = 87.45(2)degrees, V = 647.1 Angstrom(3), and Z = 1. The dimeric anion contains a centrosymmetric planar four-membered V2O2 ring with the bridging oxygens derived from the hydroxyl groups. The configuration of the anion is anti-coplanar. A frozen solution EPR spectrum with zero-field splitting and 15 line hyperfine patterns on the parallel and perpendicular features characteristic of two equivalent vanadium atoms confirms the presence of a spin triplet. This is further supported by the presence of half-field "forbidden transition" at g approximate to 4. A broad line with half-field forbidden transitions in the powder EPR spectra at X,Q-bands of the neat sample and at different temperatures shows the presence of a spin triplet ground state and a very weak intermolecular dipolar interaction. From anisotropic exchange contributions to D the magnitude of the derived exchange integral J(xy,x2-y2) is 56 cm(-1). UV-visible, ESCA, and theoretical BVS studies support the proposed molecular and electronic structure of the complex. C1 Indian Inst Technol, Reg Sophisticated Instrumentat Ctr, Madras 600036, Chennai, India. RP Subramanian, S (reprint author), NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. NR 23 TC 55 Z9 56 U1 2 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0020-1669 J9 INORG CHEM JI Inorg. Chem. PD MAR 23 PY 1998 VL 37 IS 6 BP 1336 EP 1340 DI 10.1021/ic9707467 PG 5 WC Chemistry, Inorganic & Nuclear SC Chemistry GA ZD901 UT WOS:000072735800027 ER PT J AU Chernomordik, LV Frolov, VA Leikina, E Bronk, P Zimmerberg, J AF Chernomordik, LV Frolov, VA Leikina, E Bronk, P Zimmerberg, J TI The pathway of membrane fusion catalyzed by influenza hemagglutinin: Restriction of lipids, hemifusion, and lipidic fusion pore formation SO JOURNAL OF CELL BIOLOGY LA English DT Article ID VIRAL ENVELOPE PROTEIN; PH-DEPENDENT FUSION; VIRUS HEMAGGLUTININ; CELL-FUSION; CONFORMATIONAL CHANGE; SPIKE GLYCOPROTEINS; PLASMA-MEMBRANE; KINETICS; SURFACE; MECHANISM AB The mechanism of bilayer unification in biological fusion is unclear. We reversibly arrested hemagglutinin (HA)-mediated cell-cell fusion right before fusion pore opening. A low-pH conformation of HA was required to form this intermediate and to ensure fusion beyond it. We present evidence indicating that outer monolayers of the fusing membranes were merged and continuous in this intermediate, but HA restricted lipid mixing. Depending on the surface density of HA and the membrane lipid composition, this restricted hemifusion intermediate either transformed into a fusion pore or expanded into an unrestricted hemifusion, without pores but with unrestricted lipid mixing. Our results suggest that restriction of lipid flux by a ring of activated HA is necessary for successful fusion, during which a lipidic fusion pore develops in a local and transient hemifusion diaphragm. C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. AN Frumkin Electrochem Inst, Lab Bioelectrochem, Moscow 117071, Russia. RP Chernomordik, LV (reprint author), Bldg 10,Room 10D04,10 Ctr Dr,MSC 1855, Bethesda, MD 20892 USA. OI Frolov, Vadim/0000-0002-0653-5669 NR 64 TC 255 Z9 258 U1 2 U2 9 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAR 23 PY 1998 VL 140 IS 6 BP 1369 EP 1382 DI 10.1083/jcb.140.6.1369 PG 14 WC Cell Biology SC Cell Biology GA ZE536 UT WOS:000072803100010 PM 9508770 ER PT J AU Agid, Y Chase, T Marsden, D AF Agid, Y Chase, T Marsden, D TI Adverse reactions to levodopa: drug toxicity or progression of disease? SO LANCET LA English DT Editorial Material ID DOPA C1 Hop La Pitie Salpetriere, INSERM, U289, F-75013 Paris, France. Hop La Pitie Salpetriere, Federat Neurol, F-75013 Paris, France. UCL Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England. NINDS, Bethesda, MD 20892 USA. RP Agid, Y (reprint author), Hop La Pitie Salpetriere, INSERM, U289, F-75013 Paris, France. NR 9 TC 30 Z9 31 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD MAR 21 PY 1998 VL 351 IS 9106 BP 851 EP 852 DI 10.1016/S0140-6736(05)70285-3 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA ZD047 UT WOS:000072645500007 PM 9525359 ER PT J AU Miller, KD Jones, E Yanovski, JA Shankar, R Feuerstein, I Falloon, J AF Miller, KD Jones, E Yanovski, JA Shankar, R Feuerstein, I Falloon, J TI Visceral abdominal-fat accumulation associated with use of indinavir SO LANCET LA English DT Article ID COMPUTED-TOMOGRAPHY; BODY-FAT; INFECTION; OBESITY AB Background After the addition of the protease inhibitor indinavir to combination drug regimens for HIV-1 infection, some patients have experienced an increase in abdominal girth with symptoms of abdominal fullness, distension, or bloating. We aimed to find out whether this collection of symptoms was associated with changes in abdominal fat and whether such changes were associated with indinavir use. Methods Abdominal computed tomography was used in ten HIV-1-positive patients who had such abdominal symptoms to measure total adipose tissue (TAT) and visceral adipose tissue (VAT) at the umbilicus (L4 vertebral level). The VAT:TAT ratio in the ten cases was compared with that in ten HIV-1-infected patients who had been using indinavir without abdominal symptoms for at least 6 months and ten HIV-1-infected patients who were not using indinavir. Findings The mean VAT:TAT ratios for the three groups-non-users, symptom-free indinavir users, and symptomatic indinavir users-were 0.40 (SD 0.15), 0.59 (0.18), and 0.70 (0.20), respectively (p=0.004). The VAT:TAT ratio correlated with duration of indinavir use (r=0.47, p=0.01). The mean areas of VAT for the three groups were 106 cm(2) (SD 72), 141 cm(2) (65) and 202 cm(2) (93), respectively (p=0.03). The mean body-mass index of the groups was similar, and patients in the two indinavir groups did not gain a significant amount of weight after starting the drug. Serum triglyceride values increased after starting indinavir and correlated with VAT:TAT ratios. Interpretation Our data suggest that some HIV-1-infected patients on indinavir treatment accumulate intraabdominal fat that may cause abdominal symptoms. Recent evidence suggests that other HIV-1 protease inhibitors may be associated with changes in body-fat distribution. Larger studies of protease-inhibitor treatment are needed to investigate this association further and to investigate metabolic or endocrine mechanisms that may underlie this phenomenon. C1 NICHHD, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NICHHD, Dept Radiol, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Miller, KD (reprint author), NICHHD, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, NIH, Bldg 10,Room 8C410, Bethesda, MD 20892 USA. EM kmiller@atlas.niaid.nih.gov NR 25 TC 487 Z9 491 U1 0 U2 4 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAR 21 PY 1998 VL 351 IS 9106 BP 871 EP 875 DI 10.1016/S0140-6736(97)11518-5 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA ZD047 UT WOS:000072645500014 PM 9525365 ER PT J AU Page, WF Braun, MM Caporaso, NE AF Page, WF Braun, MM Caporaso, NE TI Twinning, cancer, and genetics SO LANCET LA English DT Letter C1 Natl Acad Sci, Inst Med, Med Follow Up Agcy, Washington, DC 20418 USA. NCI, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. RP Page, WF (reprint author), Natl Acad Sci, Inst Med, Med Follow Up Agcy, Washington, DC 20418 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD MAR 21 PY 1998 VL 351 IS 9106 BP 910 EP 911 DI 10.1016/S0140-6736(05)70328-7 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA ZD047 UT WOS:000072645500061 PM 9525399 ER PT J AU Pincus, SH Cole, RL Watson-McKown, R Pinter, A Honnen, W Cole, B Wise, KS AF Pincus, SH Cole, RL Watson-McKown, R Pinter, A Honnen, W Cole, B Wise, KS TI Immunologic cross-reaction between HIV type 1 p17 and Mycoplasma hyorhinis variable lipoprotein SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SURFACE ANTIGENIC VARIATION; MONOCLONAL-ANTIBODIES; CORE PROTEIN; CELL-LINES; EXPRESSION; IDENTIFICATION; EFFICACY; GAG; LYMPHOCYTES AB Monoclonal antibodies directed against the HIV-1 matrix protein p17 that react with a component present on the surface of HIV-l-infected cells have previously been described, In this study we show that one of these monoclonal antibodies binds to persistently HIV-l-infected cell lines that are coinfected with Mycoplasma hyorhinis, but not to cell lines that are uninfected with mycoplasma. Mycoplasma-infected cells secrete HIV-1 at a higher rate, have a slight increase in cell surface expression of gp120 and gp41, and are less sensitive to immunotoxins than uninfected cells, The anti-p17 antibody binds to a protein of M. hyorhinis grown in cell-free culture, The variable expression and size of the protein among strains is typical of the variable lipoprotein (Vlp) system of M. hyorhinis, Confirmation of the reactivity of the antibody with a Vlp was provided by demonstrating its specific binding to recombinant VlpF expressed in E. coli, and to a synthetic peptide representing the carboxy-terminal region of VlpF, but not to other recombinant Vlp products or peptides, This is a true cross-reaction because the antibody also binds to recombinant p17 expressed in E. coli and the binding is inhibited by the VlpF peptide, These analyses highlight the potential of mycoplasma contamination of tissue culture cell lines to cause anomalous results, With regard to HIV-1, mycoplasma infection of cells results in increased rates of virus secretion, and introduces a potential confounding immunologic cross-reaction as well. The existence of a cell surface form of p17 is unlikely. C1 NIAID, Rocky Mt Labs, Microbial Struct & Funct Lab, Hamilton, MT 59840 USA. Univ Missouri, Sch Med, Dept Mol Microbiol & Immunol, Columbia, MO 65212 USA. Publ Hlth Res Inst, Retrovirol Lab, New York, NY 10016 USA. Univ Utah, Sch Med, Div Rheumatol, Salt Lake City, UT 84132 USA. RP Pincus, SH (reprint author), NIAID, Rocky Mt Labs, Microbial Struct & Funct Lab, 903 S 4th St, Hamilton, MT 59840 USA. FU NIAID NIH HHS [AI23884, AI31656] NR 31 TC 2 Z9 2 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAR 20 PY 1998 VL 14 IS 5 BP 419 EP 425 DI 10.1089/aid.1998.14.419 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ZC965 UT WOS:000072637000006 PM 9546801 ER PT J AU Landay, AL Bethel, J Schnittman, S AF Landay, AL Bethel, J Schnittman, S CA DATRI 003 Study Grp TI Phenotypic variability of lymphocyte populations in peripheral blood and lymph nodes from HIV-infected individuals and the impact of antiretroviral therapy SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INSITU HYBRIDIZATION; CELL SUBSETS; ACTIVATION MARKER; DOWN-REGULATION; HOMOSEXUAL MEN; T-CELLS; EXPRESSION; TYPE-1; LYMPHADENOPATHY AB This study presents immunophenotypic variation in lymphocyte populations obtained from peripheral blood and lymph nodes from individuals with early HIV disease who were enrolled in a prospective, open-label study, At baseline, there was a significantly greater percentage of B cells and significantly smaller percentage of CD8(+) cells in lymph nodes compared with peripheral blood, Evaluation of lymphocyte phenotypic markers of function, maturation, and activation at baseline revealed a significantly higher percentage of activated CD4(+) cells in lymph nodes compared with peripheral blood, whereas the percentages of activated CD8(+) cells were similar in both compartments, After an 8-week period of randomly assigned treatment, peripheral blood phenotypic marker changes included (1) a reduced proportion of activated cells (HLA-DR+) in antiretroviral-naive patients who received zidovudine (ZDV), and (2) as increased proportion of "naive" cells (CD45RA(+)) in individuals, previously administered ZDV alone, who received ZDV and didanosine (ddI) therapy, The lymph node phenotypic marker analysis showed no significant changes over the 8-week treatment period, Overall, the study demonstrates significant differences in lymphocyte subsets from lymph nodes compared with peripheral blood and suggests that further studies be performed to determine the functional significance of these phenotypic subsets. C1 Rush Presbyterian St Lukes Med Ctr, Dept Immunol Microbiol, Chicago, IL 60612 USA. WESTAT Corp, Rockville, MD 20850 USA. NIAID, Div Aids, Therapeut Res Program, NIH, Bethesda, MD 20892 USA. RP Landay, AL (reprint author), Rush Presbyterian St Lukes Med Ctr, Dept Immunol Microbiol, 1653 W Congress Pkwy, Chicago, IL 60612 USA. FU NIAID NIH HHS [N01-AI-15123] NR 47 TC 12 Z9 12 U1 1 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAR 20 PY 1998 VL 14 IS 5 BP 445 EP 451 DI 10.1089/aid.1998.14.445 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ZC965 UT WOS:000072637000009 PM 9546804 ER PT J AU Agarwal, RK Chan, CC Wiggert, B Caspi, RR AF Agarwal, RK Chan, CC Wiggert, B Caspi, RR TI Pregnant C57BL6 mice are protected from induction of experimental autoimmune uveoretinitis (EAU). SO FASEB JOURNAL LA English DT Meeting Abstract C1 NEI, Lab Immunol & Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6363 BP A1099 EP A1099 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502744 ER PT J AU Anderson, SK Passer, BJ AF Anderson, SK Passer, BJ TI NKTR association with U2AF1-RS1 and -RS2 pre-mRNA splicing factors SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, FCRDC, SAIC, Intramural Res Support Program, Frederick, MD 21702 USA. NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5249 BP A906 EP A906 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501632 ER PT J AU Arichi, T Kurokohchi, K Shirai, M Boyd, LF Marqulies, DH Berzofsky, JA AF Arichi, T Kurokohchi, K Shirai, M Boyd, LF Marqulies, DH Berzofsky, JA TI Molecular analysis of cytotoxic T lymphocyte (CTL) cross-reactivity between two major epitopes within HIV-1 GP160 in multiple haplotypes of mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6297 BP A1088 EP A1088 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502679 ER PT J AU Armstrong, JM Koshiba, M Apasov, S Sitkovsky, M AF Armstrong, JM Koshiba, M Apasov, S Sitkovsky, M TI Studies of cross-talk between TCR-triggered signaling pathways in T-lymphocytes. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5433 BP A938 EP A938 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501817 ER PT J AU Azimi, N Brown, K Bamford, RN Tagaya, Y Siebenlist, U Waldmann, TA AF Azimi, N Brown, K Bamford, RN Tagaya, Y Siebenlist, U Waldmann, TA TI HTLV-I Tax protein trans-activates IL-15 gene transcription through NF-kB in HTLV-I infected SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6163 BP A1065 EP A1065 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502544 ER PT J AU Braun, M Farber, J Kelsall, B AF Braun, M Farber, J Kelsall, B TI Selective suppression of IL-12 production by chemoattractants. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6278 BP A1085 EP A1085 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502663 ER PT J AU Chen, N Chrambach, A AF Chen, N Chrambach, A TI Extension of the preparative automated electrophoretic technique from macromolecules to subcellular-sized particles. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5962 BP A1030 EP A1030 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502344 ER PT J AU Chiaramonte, MG Schopf, L Neben, T Cheever, AW Donaldson, D Wynu, TA AF Chiaramonte, MG Schopf, L Neben, T Cheever, AW Donaldson, D Wynu, TA TI IL-13 amplifies allergic-type T helper cell 2 mediated pulmonary granuloma formation and IgE responses induced by Schistosoma eggs SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Inst Genet, Preclin Dept, Andover, MA 01810 USA. Biomed Res Inst, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6131 BP A1060 EP A1060 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502513 ER PT J AU Chumlea, WC Dwyer, J Paranandi, L Maroni, B Bergen, C Burkart, J Cockram, WC Dwyer, J Kusek, J AF Chumlea, WC Dwyer, J Paranandi, L Maroni, B Bergen, C Burkart, J Cockram, WC Dwyer, J Kusek, J CA Hemodialysis HEMO Study Grp TI Anthropometric nutritional status, education and lifestyle characteristics and energy in-take in hemodialysis patients.. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 4858 BP A838 EP A838 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501241 ER PT J AU Crowe, PD Boehme, SA Wong, T Tamraz, S Culley, BM Martin, R Conlon, PJ AF Crowe, PD Boehme, SA Wong, T Tamraz, S Culley, BM Martin, R Conlon, PJ TI Differential signaling in MBP-reactive human T cell clones (TCC) by agonist and partial agonist altered peptide ligands (APL). SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, NIH, Bethesda, MD 20892 USA. Neurocrine Biosci Inc, San Diego, CA 92121 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 3632 BP A625 EP A625 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006500015 ER PT J AU Danilkovitch, A Leonard, EJ AF Danilkovitch, A Leonard, EJ TI Macrophage stimulating protein (MSP) rescues epithelial cells from cell matrix disruption induced apoptosis (anoikis) SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Frederick, MD 21702 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5637 BP A973 EP A973 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502018 ER PT J AU Darbyshire, JF Iyer, KR Grogan, J Korzekwa, KR Trager, WF AF Darbyshire, JF Iyer, KR Grogan, J Korzekwa, KR Trager, WF TI Selectively deuterated warfarin: Substrate probe for the mechanism of aromatic hydroxylation catalyzed by cytochrome P450. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Washington, Dept Med Chem, Seattle, WA 98185 USA. NIH, Mol Carcinogenesis Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5567 BP A961 EP A961 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501949 ER PT J AU Dasso, J Posisil, R Mage, RG AF Dasso, J Posisil, R Mage, RG TI Immunohistological analysis of the development of human appendix and tonsils. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6220 BP A1075 EP A1075 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502602 ER PT J AU Fillmore, CM Fears, TR Pollak, MN Falk, RT King, J Ziegler, RG AF Fillmore, CM Fears, TR Pollak, MN Falk, RT King, J Ziegler, RG TI Insulin-like growth factors: Quality of measurement. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. McGill Univ, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 4937 BP A852 EP A852 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501320 ER PT J AU Fleming, D Jacques, P Wilson, P Wood, R AF Fleming, D Jacques, P Wilson, P Wood, R TI Heme and supplemental iron intake increase the risk of high iron stores in a free-living elderly population: The Framingham heart study. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Tufts Univ, JM USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. NHLBI, Framingham Heart Study, Framingham, MA 01701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 4758 BP A821 EP A821 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501143 ER PT J AU Gonsky, R Deem, RL Lee, DH Bream, J Young, HA Targan, SR AF Gonsky, R Deem, RL Lee, DH Bream, J Young, HA Targan, SR TI A CD2 response element which resides within the first 208BP of the interferon-gamma promoter regulates its expression in lamina propria T-cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Cedars Sinai Med Ctr, Ctr Inflammatory Bowel Dis, Los Angeles, CA 90048 USA. NCI, Expt Immunol Lab, FCRDC, Ft Detrick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6156 BP A1064 EP A1064 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502540 ER PT J AU Gran, B Martin, R Pascal, J Tranquill, L Pinilla, C Tzou, A McFarland, HF Houghten, R Hemmer, B AF Gran, B Martin, R Pascal, J Tranquill, L Pinilla, C Tzou, A McFarland, HF Houghten, R Hemmer, B TI Activation of human class-II restricted T cell clones by short peptides SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, Cellular Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RI Gran, Bruno/A-2288-2013 OI Gran, Bruno/0000-0001-6384-2342 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 3635 BP A625 EP A625 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006500019 ER PT J AU Gunshin, H Rouault, T Rogers, J Allerson, C Gollan, JL Hediger, MA AF Gunshin, H Rouault, T Rogers, J Allerson, C Gollan, JL Hediger, MA TI Regulation of the divalent cation transporter DCT1 at the mRNA level SO FASEB JOURNAL LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 4752 BP A820 EP A820 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501137 ER PT J AU Gurunathan, S Sacks, DL Seder, RA AF Gurunathan, S Sacks, DL Seder, RA TI Vaccination with lack cDNA confers protective immunity to mice infected with Leishmania major by a different mechanism than lack protein plus rIL-12 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6178 BP A1068 EP A1068 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502560 ER PT J AU Hallett, M AF Hallett, M TI Clinical and pathophysiological aspects of palatal tremor SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20816 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5629 BP A972 EP A972 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502014 ER PT J AU Hamid, EH Egan, MF Dickson, LA AF Hamid, EH Egan, MF Dickson, LA TI Detrimental effects of short term haloperidol treatment and withdrawal on striatal BDNF gene expression SO FASEB JOURNAL LA English DT Meeting Abstract C1 Howard Univ, Dept Biol, Washington, DC 20059 USA. NIMH, Neuropsychiat Res Hosp, IRP, Washington, DC 20032 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 4394 BP A758 EP A758 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006500777 ER PT J AU Harris, T Visser, M Ferrucci, L Resnick, H Tracy, R Wallace, R AF Harris, T Visser, M Ferrucci, L Resnick, H Tracy, R Wallace, R TI Heavier BMI is associated with higher IL-6 and C-reactive protein but not increased mortality. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5000 BP A864 EP A864 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501383 ER PT J AU Hatcock, KS Weng, NP Merica, R Jenkins, M Hodes, RJ AF Hatcock, KS Weng, NP Merica, R Jenkins, M Hodes, RJ TI Activation-dependent regulation of telomerase activity in murine T and B cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NIA, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN 55455 USA. RI Jenkins, Marc/G-1063-2012 OI Jenkins, Marc/0000-0001-8009-7655 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5418 BP A936 EP A936 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501801 ER PT J AU Hemmer, B Pinilla, C Gran, B Conlon, P Ling, N McFarland, HF Houghten, R Martin, R AF Hemmer, B Pinilla, C Gran, B Conlon, P Ling, N McFarland, HF Houghten, R Martin, R TI Precise prediction of class II T-cell epitopes using a combinatorial peptide library approach SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, Cellular Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RI Gran, Bruno/A-2288-2013 OI Gran, Bruno/0000-0001-6384-2342 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 3634 BP A625 EP A625 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006500016 ER PT J AU Hong, HL Devereux, TR Boorman, GA Sills, RC AF Hong, HL Devereux, TR Boorman, GA Sills, RC TI Predominant codon 61 K-ras CTA mutation in lung and harderian gland neoplasms of B6C3F1 mice exposed to chloroprene or isoprene. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, NTP, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 4711 BP A813 EP A813 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501094 ER PT J AU Hord, NG Mei, JM Winterstein, DF Phang, JM AF Hord, NG Mei, JM Winterstein, DF Phang, JM TI Nitric oxide is essential for the activation of p38 MAP kinase and induction of cyclooxygenase-2 in murine colonic epithelial cells contrasting in adenomatous polyposis coli genotype. SO FASEB JOURNAL LA English DT Meeting Abstract C1 DBS, Lab Nutr & Mol Regulat, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC, ISRP, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 4696 BP A810 EP A810 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501080 ER PT J AU Hu, GJ Wang, RYH Han, D Alter, HJ Shih, JWK AF Hu, GJ Wang, RYH Han, D Alter, HJ Shih, JWK TI Characterization of humoral and cellular immune responses against hepatitis C virus induced by DNA-based immunization. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6176 BP A1068 EP A1068 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502559 ER PT J AU Jelonek, MT Margulies, DH AF Jelonek, MT Margulies, DH TI Affinity alone of the peptide/MHC class-I complex for the TCR does not determine the extent of agonist activity in T cell stimulation. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, NIH, LI, Bethesda, MD 20892 USA. RI Margulies, David/H-7089-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 3630 BP A625 EP A625 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006500014 ER PT J AU Kant, AK Schatzkin, A AF Kant, AK Schatzkin, A TI Relation of age and self-reported chronic medical condition status with dietary nutrient intake in the US population. SO FASEB JOURNAL LA English DT Meeting Abstract C1 CUNY Queens Coll, Flushing, NY 11367 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5079 BP A877 EP A877 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501463 ER PT J AU Karnaky, KJ Masereeuw, R Henson, J Miller, DS AF Karnaky, KJ Masereeuw, R Henson, J Miller, DS TI Active xenobiotic excretion by elasmobranch rectal salt gland (RG) tubules. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Med Univ S Carolina, Dept Cell Biol & Anat, Charleston, SC 29425 USA. Dickinson Coll, Dept Biol, Carlisle, PA 17013 USA. Univ Nijmegen, Dept Pharmacol, Nijmegen, Netherlands. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Mt Desert Isl Biol Lab, Salsbury Cove, ME 04672 USA. RI Masereeuw, Roos/N-3582-2014 NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5866 BP A1014 EP A1014 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502248 ER PT J AU Karp, C Wysocka, M Cuomo, P Wahl, L Factor, R Ma, X Trinchieri, G AF Karp, C Wysocka, M Cuomo, P Wahl, L Factor, R Ma, X Trinchieri, G TI Marked suppression of IL-12 during endotoxin tolerance SO FASEB JOURNAL LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD 21205 USA. Wistar Inst, Philadelphia, PA 19104 USA. NIDR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6173 BP A1067 EP A1067 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502557 ER PT J AU Kim, GH Ecelbarger, CA Knepper, M Packer, R AF Kim, GH Ecelbarger, CA Knepper, M Packer, R TI Rat renal outer medullary BSC-1 and Na/K-ATPase protein levels increase in response to sodium loading but not acid loading. SO FASEB JOURNAL LA English DT Meeting Abstract C1 George Washington Univ, Washington, DC 20052 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 3707 BP A638 EP A638 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006500091 ER PT J AU Koslow, SH Huerta, MF AF Koslow, SH Huerta, MF TI Integrating neuroscience data across levels of analysis and species. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 3648 BP A628 EP A628 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006500032 ER PT J AU Kullberg, MC Ward, JM Gorelick, PL Jankovic, DL Sher, A AF Kullberg, MC Ward, JM Gorelick, PL Jankovic, DL Sher, A TI Helicobacter hepaticus triggers inflammatory bowel disease in IL-10-deficient mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, LPD, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Anim Hlth Diagnost Lab, Frederick, MD 21702 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6168 BP A1066 EP A1066 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502550 ER PT J AU Kultz, D Madhany, S Burg, MB AF Kultz, D Madhany, S Burg, MB TI Hyperosmotic induction of growth arrest in murine kidney cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, LKEM, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5925 BP A1024 EP A1024 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502307 ER PT J AU Laban, O DeRijk, R Sternberg, EM AF Laban, O DeRijk, R Sternberg, EM TI Differential corticosteroid sensitivity of pro- and anti-inflammatory cytokines SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. Leiden Amsterdam Ctr Drug Res, Div Med Pharmacol, Leiden, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6087 BP A1052 EP A1052 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502468 ER PT J AU Laithwaite, JE Benn, SJ Yamate, J FitzGerald, DJ LaMarre, J AF Laithwaite, JE Benn, SJ Yamate, J FitzGerald, DJ LaMarre, J TI Increased resistance to Pseudomonas exotoxin A coincides with decreased LRP expression in HS-P macrophages. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Guelph, Dept Biomed Sci, Guelph, ON N1G 2W1, Canada. Univ Osaka Prefecture, Coll Agr, Dept Vet Pathol, Sakai, Osaka 593, Japan. NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 4674 BP A806 EP A806 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501057 ER PT J AU Li, TK Bierer, BE AF Li, TK Bierer, BE TI FK506- and calmodulin-independent binding of the immunophilin FKBP51 to calcineurin SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5438 BP A939 EP A939 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501820 ER PT J AU Lillard, JW Boyaka, PN Kweon, M Yamamoto, M Yamamoto, S Chertov, O Oppenheim, JJ AF Lillard, JW Boyaka, PN Kweon, M Yamamoto, M Yamamoto, S Chertov, O Oppenheim, JJ TI Mucosal administration of defensins with antigen induces Th1- and IL-4 independent Th2-type responses SO FASEB JOURNAL LA English DT Meeting Abstract C1 Immunobiol Vaccine Ctr, Birmingham, AL 35294 USA. Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5265 BP A909 EP A909 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501647 ER PT J AU Losi, JM Ogasawara, K Taniguchi, T Taki, S Waldmann, TA Tagaya, Y AF Losi, JM Ogasawara, K Taniguchi, T Taki, S Waldmann, TA Tagaya, Y TI IL-15: A seemingly indispensable factor for bone marrow-derived NK cell maturation. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Met Br, NIH, Bethesda, MD 20892 USA. Univ Tokyo, Fac Med, Dept Immunol, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6162 BP A1065 EP A1065 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502546 ER PT J AU Malik, M Heath, ME Goldstein, DS AF Malik, M Heath, ME Goldstein, DS TI Pre- and post-dive levels of plasma catechols in white whales. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Biodivers Res & Appl Assn, San Diego, CA 92192 USA. NIH, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 3930 BP A677 EP A677 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006500315 ER PT J AU Martin, R Vergelli, M Gran, B Ling, N Conlon, P McFarland, HF Hemmer, B AF Martin, R Vergelli, M Gran, B Ling, N Conlon, P McFarland, HF Hemmer, B TI Predictable TCR antigen recognition based on peptide scans leads to the identification of agonist ligands with no sequence homology SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, Cellular Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RI Gran, Bruno/A-2288-2013 OI Gran, Bruno/0000-0001-6384-2342 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 3631 BP A625 EP A625 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006500017 ER PT J AU Mcdyer, JF Goletz, TJ Seder, RA AF Mcdyer, JF Goletz, TJ Seder, RA TI Soluble CD40 ligand matures monocyte-derived dendritic cells and induces dendritic cell production of beta-chemokines and GM-CSF SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 3646 BP A627 EP A627 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006500028 ER PT J AU Mcintee, EJ Wagner, CR Giordano, V Jeang, KT Chiang, PK AF Mcintee, EJ Wagner, CR Giordano, V Jeang, KT Chiang, PK TI Amino acid phosphoramidates of antiviral 3-deazaadenosine analogs exhibit high potency and low cytotoxicity. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Minnesota, Dept Med Chem, Minneapolis, MN 55455 USA. NIAID, NIH, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Washington, DC 20307 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 4479 BP A773 EP A773 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006500862 ER PT J AU McKee, MD Clay, TM Custer, MC Wunderlich, J Rosenberg, SA Nishimura, MI AF McKee, MD Clay, TM Custer, MC Wunderlich, J Rosenberg, SA Nishimura, MI TI Expansion of melanoma-reactive T cells from peptide-stimulated PBL of vaccinated patients is oligoclonal in short term cultures. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5260 BP A908 EP A908 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501641 ER PT J AU Mongini, P Vilensky, M Highet, P Inman, J AF Mongini, P Vilensky, M Highet, P Inman, J TI BCR : CD21 coligation lowers the affinity thresholds for BCR-mediated upregulation of DR and CD86 in human B cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 NYU Med Ctr, Hosp Joint Dis, Dept Rheumatol, Bethesda, MD USA. NIH, Immunol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6251 BP A1080 EP A1080 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502635 ER PT J AU Moratz, C Harrison, K Riva, A Kehrl, JH AF Moratz, C Harrison, K Riva, A Kehrl, JH TI Analysis of B cell specific activator protein (BSAP) transgenic mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, LIR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6224 BP A1076 EP A1076 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502607 ER PT J AU Naidu, M Ryan, JJ McReynolds, LJ Paul, WE Chu, CC AF Naidu, M Ryan, JJ McReynolds, LJ Paul, WE Chu, CC TI Interleukin-4 induction of Fig1 in B cells: Role of STAT6. SO FASEB JOURNAL LA English DT Meeting Abstract C1 N Shore Univ Hosp, NYU, Sch Med, Manhasset, NY 11030 USA. NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6269 BP A1083 EP A1083 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502651 ER PT J AU Nebeling, L Hord, NG AF Nebeling, L Hord, NG TI Development of a review of basic epidemiologic concepts for undergraduate nutrition education: studies of vegetable and fruit consumption and breast cancer risk as illustrative examples. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, 5 A Day Better Hlth Program, Bethesda, MD 20892 USA. NCI, Lab Nutr & Mol Regulat, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 4771 BP A823 EP A823 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501153 ER PT J AU Noben-Trauth, N Sacks, D Paul, WE AF Noben-Trauth, N Sacks, D Paul, WE TI IL-4 and IL-4 receptor deficient mice reveal parasite strain differences in the ability to control Leishmania major infection. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Labs Immunol & Parasit Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6271 BP A1084 EP A1084 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502654 ER PT J AU Oh, CK Cho, JJ Vliagoftis, H Metcalfe, DD AF Oh, CK Cho, JJ Vliagoftis, H Metcalfe, DD TI Identification and characterization of an inducible mast cell gene in a subtraction library SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harbor UCLA Med Ctr, Dept Pediat, Div Allergy & Immunol, Torrance, CA 90509 USA. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RI Vliagoftis, Harissios/C-6480-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5199 BP A898 EP A898 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501584 ER PT J AU Okazaki, H Zhang, J Siraganian, RP AF Okazaki, H Zhang, J Siraganian, RP TI Syk tyrosine kinase independent activation of MAP kinase by G-protein-coupled-receptor stimulation in mast cell SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5189 BP A896 EP A896 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501573 ER PT J AU Phung, QH Winter, DB Bohr, VA Gearhart, PJ AF Phung, QH Winter, DB Bohr, VA Gearhart, PJ TI Altered spectra of hypermutation in antibodies from mismatch repair-deficient mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5126 BP A885 EP A885 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501509 ER PT J AU Polakova, K Plaksin, D Margulies, DH AF Polakova, K Plaksin, D Margulies, DH TI Antibodies directed against MHC/peptide complexes: Similarities to a T cell receptor with the same specificity. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RI Margulies, David/H-7089-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6305 BP A1089 EP A1089 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502686 ER PT J AU Segal, BM Shevach, EM AF Segal, BM Shevach, EM TI The innate immune system controls susceptibility to experimental allergic encephalomyelitis (EAE) by regulating the interleukin (IL)-12/IL-10 balance SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6359 BP A1099 EP A1099 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502742 ER PT J AU Sehgal, D Schiaffella, E Anderson, AO Mage, RG AF Sehgal, D Schiaffella, E Anderson, AO Mage, RG TI Single cell PCR reveals rearranged V-H with germline sequences in spleens of immunized adult rabbits SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. USA, Med Res Inst Infect Dis, Appl Res Div, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5122 BP A885 EP A885 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501507 ER PT J AU Shen, R Wynshaw-Boris, A Barlow, C Hodes, R AF Shen, R Wynshaw-Boris, A Barlow, C Hodes, R TI Characterization of the immune system in a mouse mutant model of ataxia-telangiectasia. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. NIH, Natl Ctr Human Genome REs, Lab Genet Dis Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5335 BP A922 EP A922 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501718 ER PT J AU Shi, SS Day, RM Chedid, M Blumberg, IB Suzuki, YI AF Shi, SS Day, RM Chedid, M Blumberg, IB Suzuki, YI TI Lipoic acid-mediated signal transduction. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. NCI, NIH, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 4725 BP A815 EP A815 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501109 ER PT J AU Silver, P Tarrant, T Chan, CC Wiggert, B Magram, J Caspi, R AF Silver, P Tarrant, T Chan, CC Wiggert, B Magram, J Caspi, R TI Endogenous IL-12 is required for induction and expression of experimental autoimmune uveitis. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. Hoffmann La Roche Inc, Dept Biotechnol, Nutley, NJ 07110 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6277 BP A1085 EP A1085 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502660 ER PT J AU Sloan-Lancaster, J Presley, JF Ellenberg, J Lippincott-Schwartz, J Samelson, LE AF Sloan-Lancaster, J Presley, JF Ellenberg, J Lippincott-Schwartz, J Samelson, LE TI Dynamics and stability of ZAP-70 in different intracellular compartments. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5415 BP A935 EP A935 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501799 ER PT J AU Steinbrecher, A Scott, D Pak, SH Izikson, L Martin, R Jendoubi, M Brocke, S AF Steinbrecher, A Scott, D Pak, SH Izikson, L Martin, R Jendoubi, M Brocke, S TI Partial resistance to experimental autoimmunity in invariant chain deficient mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6081 BP A1051 EP A1051 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502462 ER PT J AU Sun, B Sun, SH Rizzo, LV Chan, CC Wiggert, B Caspi, RR AF Sun, B Sun, SH Rizzo, LV Chan, CC Wiggert, B Caspi, RR TI Experimental autoimmune uveitis is associated with conversion from a Th2-like to a Th1-like response in susceptible, but not in resistant mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RI Rizzo, Luiz Vicente/B-4458-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6357 BP A1098 EP A1098 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502738 ER PT J AU Sun, SH Silver, PB Du, Y Chan, CC Caspi, RR Wilder, RL Remmers, EF AF Sun, SH Silver, PB Du, Y Chan, CC Caspi, RR Wilder, RL Remmers, EF TI Genetic analysis of experimental autoimmune uveoretinitis (EAU) in rats. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NEI, Immunol Lab, Bethesda, MD 20892 USA. NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6384 BP A1103 EP A1103 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502769 ER PT J AU Swanson, CA Alavanja, MCR Brownson, RC AF Swanson, CA Alavanja, MCR Brownson, RC TI Leanness and lung cancer risk among women. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. St Louis Univ, Hlth Sci Ctr, St Louis, MO 63108 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5068 BP A875 EP A875 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501452 ER PT J AU Trump, BF Phelps, PC Harris, CC Chang, SH AF Trump, BF Phelps, PC Harris, CC Chang, SH TI Mechanism of action of genes related to cell death in neoplasia. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5580 BP A963 EP A963 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501964 ER PT J AU Ufret-Vincenty, R Pak, SH Quigley, L Wucherfennig, K Brocke, S AF Ufret-Vincenty, R Pak, SH Quigley, L Wucherfennig, K Brocke, S TI Induction of experimental autoimmune encephalomyelitis by pathogen derived peptides. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, NIB, Neurol Dis Sect, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6310 BP A1090 EP A1090 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502692 ER PT J AU Watson, ML Campbell, EM White, AM Yoshimura, T Westwick, J AF Watson, ML Campbell, EM White, AM Yoshimura, T Westwick, J TI Rantes and MCP-1 expression in antigen challenged guinea-pig airways. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 4597 BP A793 EP A793 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006500980 ER PT J AU Weng, NP Granger, L Hodes, RJ AF Weng, NP Granger, L Hodes, RJ TI Telomere lengthening and telomerase activation during human B cell differentiation. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA, LI, GRC, NIH, Baltimore, MD 21224 USA. NCI, EIB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6201 BP A1072 EP A1072 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502586 ER PT J AU Wood, RJ Fleming, DJ Jacques, PF Wilson, PWF AF Wood, RJ Fleming, DJ Jacques, PF Wilson, PWF TI Iron status of the elderly Framingham Heart Study Cohort: An iron-replete population with a high prevalence of elevated iron stores. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Tufts Univ, USDA, JM HNRCA, Boston, MA 02111 USA. NHLBI, Framingham Heart Study, Framingham, MA 01701 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 4898 BP A846 EP A846 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501281 ER PT J AU Wu, C Maeda, H Contursi, C Seder, R AF Wu, C Maeda, H Contursi, C Seder, R TI Differential requirement for interferon consensus sequence binding protein (ICSBP) in regulating production of IL-12 and enhancement of Th1 priming in response to IFN gamma SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6275 BP A1084 EP A1084 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502656 ER PT J AU Yang, T Schnermann, JB Briggs, JB AF Yang, T Schnermann, JB Briggs, JB TI Regulation of renal medullary cyclooxygenase 2 by hyperosmolality in vitro and in vivo SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. NIDDK, DKUHD, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5935 BP A1026 EP A1026 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502318 ER PT J AU Zhou, P Seder, RA AF Zhou, P Seder, RA TI CD40 ligand is not essential for induction of type 1 cytokine responses or protective immunity following primary or secondary infection with Histoplasma capsulatum SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6127 BP A1059 EP A1059 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502508 ER PT J AU Zhu, X McHugh, L Mage, M AF Zhu, X McHugh, L Mage, M TI Obligatory class II MHC superdimers and supertrimers show enhanced efficacy in T cell stimulation SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6309 BP A1090 EP A1090 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502691 ER PT J AU Aphasizheva, IY Dolgikh, DA Abdullaev, ZK Uversky, VN Kirpichnikov, MP Ptitsyn, OB AF Aphasizheva, IY Dolgikh, DA Abdullaev, ZK Uversky, VN Kirpichnikov, MP Ptitsyn, OB TI Can grafting of an octapeptide improve the structure of a de novo protein? SO FEBS LETTERS LA English DT Article DE de novo protein; molten globule; protein expression; protein design; interferon ID POLYACRYLAMIDE-GEL ELECTROPHORESIS; DENOVO PROTEIN; DESIGN; ALBEBETIN; CHROMATOGRAPHY; SEPARATION; STABILITY AB Structural properties and conformational stability of de novo proteins - albebetin and albeferon (albebetin with a grafted interferon fragment) - were studied by means of CD spectroscopy, gel filtration and urea-induced unfolding, The results allow us to conclude that albebetin possesses the properties of the molten globule state, Grafting of the octapeptide to the N-terminus of this de novo protein affects its structure, We show here that albeferon maintains a secondary structure content of albebetin; it becomes more compact and much more stable toward urea-induced unfolding as compared to albebetin and even possesses some weak tertiary structure (at least around Tyr(7)), This means that the structure of the artificial protein albebetin can be improved by a simple procedure of octapeptide grafting to its N-terminus. (C) 1998 Federation of European Biochemical Societies. C1 Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow 117871, Russia. Russian Acad Sci, Inst Prot Res, Pushchino 142292, Moscow Region, Russia. NCI, Lab Expt & Computat Biol, NIH, Bethesda, MD 20892 USA. RP Aphasizheva, IY (reprint author), Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow 117871, Russia. RI Uversky, Vladimir/F-4515-2011; Dolgikh, Dmitry/F-2369-2014; OI Uversky, Vladimir/0000-0002-4037-5857; Dolgikh, Dmitry/0000-0002-9880-7202 NR 26 TC 11 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAR 20 PY 1998 VL 425 IS 1 BP 101 EP 104 DI 10.1016/S0014-5793(98)00201-4 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA ZE342 UT WOS:000072783000020 PM 9541015 ER PT J AU Rund, D Dagan, M Dalyot-Herman, N Kimchi-Sarfaty, C Schoenlein, PV Gottesman, MM Oppenheim, A AF Rund, D Dagan, M Dalyot-Herman, N Kimchi-Sarfaty, C Schoenlein, PV Gottesman, MM Oppenheim, A TI Efficient transduction of human hematopoietic cells with the human multidrug resistance gene 1 via SV40 pseudovirions SO HUMAN GENE THERAPY LA English DT Article ID HUMAN MDR1 GENE; SIMIAN VIRUS-40; P-GLYCOPROTEIN; RETROVIRAL TRANSFER; CONFERS RESISTANCE; MESSENGER-RNA; MARROW-CELLS; BONE-MARROW; STEM-CELLS; EXPRESSION AB Transduction of MDR1 may be of use in chemoprotection of normal bone marrow (BM) cells during treatment of malignancies, or as a selectable marker for the transfer of other genes into the BM, a critical target for the cure of many diseases, To that aim, the human multidrug resistance gene MDR1 was cloned into an SV40 pseudoviral vector containing the SV40 origin of replication (ori) and encapsidation signal (ses), and the plasmid was encapsidated in COS cells as SV40/MDR1 pseudovirions, Expression of the human MDR1 gene was demonstrated in murine MEL cells infected with SV40/MDR1 pseudovirions, using a monoclonal antibody (MPK16) specific for the human 170-kD P-glycoprotein, Functional P-glycoprotein was demonstrated by resistance to colchicine in NIH-3T3 cells infected with SV40/MDR1 pseudovirions, Activity of P-glycoprotein was assayed by rhodamine-123 dye exclusion and fluorescence-activated cell sorter analysis (FAGS) in various cell types including hematopoietic cells, Highly efficient gene transfer and expression was demonstrated in all murine and human cell types tested, including primary human BM cells. Using multiplicities of infection (moi) of 1-2, over 95% of cells were found to become MDR1(+). The percent of MDR1(+) cells was proportional to the moi. We conclude that the SV40 pseudoviral vector is efficient for gene transmission into human hematopoietic cells. C1 Hadassah Univ Hosp, Dept Hematol, IL-91120 Jerusalem, Israel. Hebrew Univ Jerusalem, Sch Med, Dept Hematol, IL-91010 Jerusalem, Israel. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Rund, D (reprint author), Hadassah Univ Hosp, Dept Hematol, POB 12000, IL-91120 Jerusalem, Israel. NR 35 TC 30 Z9 31 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAR 20 PY 1998 VL 9 IS 5 BP 649 EP 657 DI 10.1089/hum.1998.9.5-649 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA ZE866 UT WOS:000072839500006 PM 9551613 ER PT J AU Cohen, BE AF Cohen, BE TI Amphotericin B toxicity and lethality: a tale of two channels SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE Amphotericin B; K+ leakage; toxicity ID LEISHMANIA-MEXICANA PROMASTIGOTES; PLASMA-MEMBRANE VESICLES; CANDIDA-ALBICANS; POLYENE ANTIBIOTICS; CELL-DEATH; PERMEABILITY; DAMAGE; TRANSFORMATION; NEPHROTOXICITY; KETOCONAZOLE AB In spite of its toxic side effects, Amphotericin B (AmB) is the most effective drug in the treatment of visceral Leishmaniasis and systemic fungus infections. However, the toxic side effects of this drug can be substantially reduced when delivered as a complex with liposomes and other lipidic systems. Nonetheless, the mechanisms of AmB antifungal activity and of toxicity to the host are not yet fully understood. The classical pore model of AmB action postulates that a single type of channel permeable to monovalent cations and anions is responsible for the AmB fungicidal and leishmanicidal action, as well as for its toxic side effects. Thus, the loss of membrane cation selectivity, caused by AmB aqueous pores has been proposed as the primary cause of fungal cell death. The hypothesis has been that fungal cell death results from intracellular acidification associated with K+ leakage. However, this mechanism of AmB action has been challenged by several investigators on the basis that low AmB concentrations cause K+ leakage from sensitive cells which is dissociated from the lethal effects produced by higher AmB concentrations. Our own studies indicate that the formation of aqueous pores by AmB in sterol-containing liposomes is always preceded by the formation of non-aqueous channels. At low AmB concentrations or in the absence of sterols, AmB non-aqueous channels do not evolve to form aqueous pores, nor is the K+ leakage they produce lethal to cells. It is only when a 'critical' concentration of AmB is reached at the membrane that non-aqueous channels interact with ergosterol or cholesterol to form transmembrane aqueous pores. The pore diameter of the channels formed by AmB is critical for AmB toxicity or lethality because non-aqueous channels are only permeable to urea and monovalent cations, whereas AmB aqueous pores are permeable to monovalent cations and anions (including H+ and OH-) and divalent cations such as Ca2+. In fact, leishmanias are killed rapidly by colloid osmotic lysis due to a net salt influx across the AmB aqueous pores. Fungal cells are protected from osmotic lysis by the presence of a cell wall. but an increased H+/OH- permeability across AmB aqueous pores leads to an elevation of intracellular pH which then results in membrane damage. In host mammalian cells, non-aqueous channels appear to be responsible for some of the toxic but reversible side effects produced by AmB. However, more acute and damaging effects such as those exerted by AmB in kidney tubular cells may be caused by increased salt, Ca2+ and/or H+ permeability across aqueous pores. A sustained collapse of pH and Ca2+ gradients is a mechanism which is also exhibited by molecular inducers of programmed cell death (apoptosis) in eucaryotic cells. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NIDDK, Cell Biol & Genet Lab, NIH, Bethesda, MD 20892 USA. Cent Univ Venezuela, Fac Sci, Inst Expt Biol, Caracas 1041, Venezuela. RP Cohen, BE (reprint author), Uniformed Serv Univ, Sch Med, Dept Anat & Cell Biol, Bldg B,Room B2200,4301 Jones Bridge Rd, Bethesda, MD 20819 USA. NR 51 TC 75 Z9 79 U1 1 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARM JI Int. J. Pharm. PD MAR 20 PY 1998 VL 162 IS 1-2 BP 95 EP 106 DI 10.1016/S0378-5173(97)00417-1 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZF682 UT WOS:000072921500013 ER PT J AU Rosin, O Koch, C Schmitt, I Semmes, OJ Jeang, KT Grassmann, R AF Rosin, O Koch, C Schmitt, I Semmes, OJ Jeang, KT Grassmann, R TI A human T-cell leukemia virus Tax variant incapable of activating NF-KB retains its immortalizing potential for primary T-lymphocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HTLV-I TAX; HERPESVIRUS-SAIMIRI; KAPPA-B; RESPONSE ELEMENT; RAT FIBROBLASTS; BINDING-PROTEIN; TRANSFORMATION; GENE; PATHWAY; TRANSCRIPTION AB The human T-cell leukemia virus type 1 (HTLV-1) transactivator (Tax) has been shown to interfere with regulated cellular proliferation. Many studies have focused on the ability of Tax to transform rodent fibroblasts; however, none has defined the molecular requirements for Tax transformation of human lymphoid cells, We show here that tax induces permanent growth of human primary T-lymphocytes by using a transformation/immortalization defective rhadinovirus vector, The cells phenotypically resemble HTLV-immortalized lymphocytes and contain episomally persisting recombinant rhadinoviral sequences, which stably express functional Tax protein. As Tax can activate major cellular signal transducing pathways including NF-kappa B and cAMP-responsive element binding protein (CREB), we asked for the relevance of these routes in the immortalization of human lymphocytes. By using Tax mutants that either activate exclusively CREB/activating transcription factor or are defective in activating this signaling pathway, we delineated that Tax can induce immortalization of primary human T-lymphocytes through a mechanism independent of NF-kappa B activation. C1 Univ Erlangen Nurnberg, Inst Klin & Mol Virol, D-91054 Erlangen, Germany. NIAID, Mol Virol Sect, NIH, Bethesda, MD 20892 USA. RP Grassmann, R (reprint author), Univ Erlangen Nurnberg, Inst Klin & Mol Virol, Schlossgarten 4, D-91054 Erlangen, Germany. RI Jeang, Kuan-Teh/A-2424-2008 NR 42 TC 68 Z9 71 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 20 PY 1998 VL 273 IS 12 BP 6698 EP 6703 DI 10.1074/jbc.273.12.6698 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZE277 UT WOS:000072775900017 PM 9506967 ER PT J AU Tsuji, T Duh, FM Latif, F Popescu, NC Zimonjic, DB McBride, J Matsuo, K Ohyama, H Todd, R Nagata, E Terakado, N Sasaki, A Matsumura, T Lerman, MI Wong, DTW AF Tsuji, T Duh, FM Latif, F Popescu, NC Zimonjic, DB McBride, J Matsuo, K Ohyama, H Todd, R Nagata, E Terakado, N Sasaki, A Matsumura, T Lerman, MI Wong, DTW TI Cloning, mapping, expression, function, and mutation analyses of the human ortholog of the hamster putative tumor suppressor gene doc-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IN-SITU HYBRIDIZATION; RETINOIC ACID; LOCALIZATION; EOSINOPHILS; KERATIN-19; RECEPTORS; CANCER; ALPHA AB doc-1 is a putative tumor suppressor gene isolated and identified from the hamster oral cancer model, Here, we report the molecular cloning and the functional characterization of the human ortholog of the hamster doc-l gene, Human doc-l cDNA is 1.6 kilobase pairs in length and encodes for a 115-amino acid polypeptide (12.4 kDa, pi 9.53). Sequence analysis showed 98% identity between human and hamster doc-l protein sequences. DOC-1 is expressed in all normal human tissues examined. In oral keratinocytes, expression of DOC-1 is restricted to normal oral keratinocytes, By immunostaining of normal human mucosa, DOC-1 is detected in both the cytoplasm and nuclei of basal oral keratinocytes; while in suprabasilar cells, it is primarily found in the nuclei, Human oral cancers in vivo did not exhibit immunostaining for DOC-1, Like murine DOC-1, human DOC-1 associates with DNA polymerase alpha/primase and mediates the phosphorylation of the large p180 catalytic subunit, suggesting it may be a potential regulator of DNA replication in the S phase of the cell cycle, Using a human doc-l cosmid as a probe, human doc-l is mapped to chromosome 12q24. We identified four exons in the entire human doc-l gene and determined the intron-exon boundaries. By polymerase chain reaction and direct sequencing, we examined premalignant oral lesion and oral cancer cell lines and found no intragenic mutations. C1 Harvard Univ, Sch Dent Med, Div Oral Pathol, Lab Mol Pathol, Boston, MA 02115 USA. SAIC, Intramural Res Support Program, Frederick, MD USA. NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Immunobiol Lab, Frederick, MD 21702 USA. NCI, Div Basic Sci, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Okayama Univ, Sch Dent, Dept Oral & Maxillofacial Surg 2, Okayama 700, Japan. RP Wong, DTW (reprint author), Harvard Univ, Sch Dent Med, Div Oral Pathol, Lab Mol Pathol, 188 Longwood Ave, Boston, MA 02115 USA. FU NIDCR NIH HHS [2 RO1 DE08680-08, 1 R29 DE11983-01, 1 PO1 DE12467] NR 26 TC 55 Z9 62 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 20 PY 1998 VL 273 IS 12 BP 6704 EP 6709 DI 10.1074/jbc.273.12.6704 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZE277 UT WOS:000072775900018 PM 9506968 ER PT J AU Shibutani, M Lazarovici, P Johnson, AC Katagiri, Y Guroff, G AF Shibutani, M Lazarovici, P Johnson, AC Katagiri, Y Guroff, G TI Transcriptional down-regulation of epidermal growth factor receptors by nerve growth factor treatment of PC12 cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHEOCHROMOCYTOMA CELLS; PROTEIN-BINDING; GENE PROMOTER; HUMAN P53; IDENTIFICATION; LINE; DIFFERENTIATION; ACTIVATION; RESPOND AB Treatment of PC12 cells with nerve growth factor leads to a decrease in the number of epidermal growth factor receptors on the cell membrane, The mRNA for the epidermal growth factor receptor decreases in a comparable fashion. This decrease appears due to a decrease in the transcription of the epidermal growth factor receptor gene because first, there is no difference in the stability of the epidermal growth factor receptor mRNA, second, newly transcribed epidermal growth factor receptor mRNA is decreased in nerve growth factor-differentiated cells, and third, constructs containing the promoter region of the epidermal growth factor receptor gene are transcribed much less readily in nerve growth factor-differentiated cells than in untreated cells, The decreases in mRNA are not seen in the p140(trk)-deficient variant PC12nnr5 cells nor in cells containing either dominant-negative Ras or dominant-negative Src, Treatment with nerve growth factor also increases the cellular content of GCF2, a putative transcription factor inhibitory for the transcription of the epidermal growth factor receptor gene. The increase in GCF2, like the decrease in the epidermal growth factor receptor mRNA, is not seen in PC12nnr5 cells nor in cells expressing either dominant-negative Ras or dominant-negative Src, The results suggest that nerve growth factor-induced down-regulation of the epidermal growth factor receptor is under transcriptional control, is p140(trk), Ras-, and Src-dependent, and may involve transcriptional repression by GCF2. C1 NICHD, Growth Factors Sect, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Guroff, G (reprint author), NICHD, Growth Factors Sect, NIH, Bldg 49,Rm 5A64, Bethesda, MD 20892 USA. RI Shibutani, Makoto/C-2510-2013 NR 33 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 20 PY 1998 VL 273 IS 12 BP 6878 EP 6884 DI 10.1074/jbc.273.12.6878 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZE277 UT WOS:000072775900041 PM 9506991 ER PT J AU Salvatore, P Hanash, CR Kido, Y Imai, Y Accili, D AF Salvatore, P Hanash, CR Kido, Y Imai, Y Accili, D TI Identification of sirm, a novel insulin-regulated SH3 binding protein that associates with Grb-2 and FYN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR GENE; SH3-DOMAIN-BINDING PROTEIN; TYROSINE PHOSPHORYLATION; SOS-GRB2 COMPLEX; C-SRC; SEQUENCE; DOMAINS; ABL; DISASSOCIATION; ELEGANS AB We have previously developed a mouse model of insulin-resistant diabetes by targeted inactivation of the insulin receptor gene. During studies of gene expression in livers of insulin receptor-deficient mice, we identified a novel cDNA, which me have termed sirm (Son of Insulin Receptor Mutant mice), sirm is largely, albeit not exclusively, expressed in insulin-responsive tissues, Insulin is a potent modulator of sirm expression, and sirm mRNA levels correlate with tissue sensitivity to insulin. The product of the sirm gene is a serine/threonine-rich protein with several proline-rich motifs and an NPNY motif, conforming to the consensus sequence recognized by the phosphotyrosine binding domains of insulin receptor substrate and Shc proteins, However, Sirm bears no extended homologies with other known proteins. Based on the sequences of the proline-rich domains, we sought to determine whether Sirm binds to the SH3 domains of FYN and Grb-8, We demonstrate here that Sirm binds to FYN and Grb-8 in 3TS-L1 adipocytes and that insulin treatment results in the dissociation of the Sirm FYN and Sirm-Grb-2 complexes. We also show that Sirm is a substrate for the kinase activity of FYN in vitro, Based on the patterns of expression of sirm, its regulation by insulin, and the interactions with molecules in the insulin signaling pathway, we surmise that Sirm plays a role in modulating tissue sensitivity to insulin. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Sch Med, Div Endocrinol, Chapel Hill, NC 27514 USA. RP Accili, D (reprint author), Bldg 10,Rm 10D18, Bethesda, MD 20892 USA. OI SALVATORE, Paola/0000-0002-7294-9253 NR 30 TC 11 Z9 13 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 20 PY 1998 VL 273 IS 12 BP 6989 EP 6997 DI 10.1074/jbc.273.12.6989 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZE277 UT WOS:000072775900056 PM 9507006 ER PT J AU Sukhodolets, MV Jin, DJ AF Sukhodolets, MV Jin, DJ TI RapA, a novel RNA polymerase-associated protein, is a bacterial homolog of SWI2/SNF2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPT CLEAVAGE FACTORS; YEAST SWI/SNF COMPLEX; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; PUTATIVE HELICASES; GLOBAL ACTIVATOR; DNA; BINDING; GENE; FAMILY AB We have identified a novel Escherichia coli RNA polymerase (RNAP)-associated protein, an ATPase named RapA. Almost all of this 110-kDa protein in the cell copurifies with RNAP holoenzyme as a 1:1 complex. Purified to homogeneity, RapA also forms a stable complex with RNAP, as if it were a subunit of RNAP. The ATPase activity of RapA is stimulated by binding to RNAP, and thus, RapA and RNAP interact physically as well as functionally. Interestingly, RapA is a homolog of the SWI/SNF family of eukaryotic proteins whose members are involved in transcription activation, nucleosome remodeling, and DNA repair. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Jin, DJ (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37,Rm 2E14,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 49 TC 43 Z9 44 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 20 PY 1998 VL 273 IS 12 BP 7018 EP 7023 DI 10.1074/jbc.273.12.7018 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZE277 UT WOS:000072775900059 PM 9507009 ER PT J AU Fridell, YWC Villa, J Attar, EC Liu, ET AF Fridell, YWC Villa, J Attar, EC Liu, ET TI GAS6 induces Axl-mediated chemotaxis of vascular smooth muscle SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR TYROSINE KINASE; ARREST-SPECIFIC GENE-6; GROWTH-FACTOR; PROTEIN-S; CELLS; MIGRATION; SKY; PRODUCT; CLONING; LIGAND AB Atherosclerosis and arterial restenosis are disease processes involving the accumulation of vascular smooth muscle cells following vascular injury. Key events leading to these processes are migration and proliferation of these cells. Here, we demonstrate that GAS6, encoded by the growth arrest-specific gene 6, induces a directed migration (chemotaxis) of both rat and human primary vascular smooth muscle cells while showing only marginal mitogenic potential in human vascular smooth muscle cells. GAS6 stimulation induces Axl autophosphorylation in human vascular smooth muscle cells, indicating that specific GAS6-Axl interactions may be associated with GAS6-directed chemotaxis, To test this hypothesis, vascular smooth muscle cells overexpressing Axl were generated by gene transfer and assessed for their ability to migrate along a GAS6 gradient. These Axl overexpressors exhibited 2-5-fold increased sensitivity to GAS6-induced chemotaxis, Furthermore, vascular smooth muscle cells expressing the kinase dead mutant of Axl or exposure to the soluble Axl extracellular domain showed attenuated GAS6-induced migration, Taken together, these results suggest that GAS6 is a novel chemoattractant that induces Axl-mediated migration of vascular smooth muscle cells, The separation of mitogenesis from migration provided by this study may enhance the molecular dissection of cell migration in vascular damage. C1 Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Liu, ET (reprint author), NCI, Div Clin Sci, Sect Mol Signalling & Oncogenesis, NIH, 10-6C206 10 Ctr Dr,MSC 1585, Bethesda, MD 20892 USA. RI Liu, Edison/C-4141-2008 FU NCI NIH HHS [CA49240] NR 29 TC 136 Z9 136 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 20 PY 1998 VL 273 IS 12 BP 7123 EP 7126 DI 10.1074/jbc.273.12.7123 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZE277 UT WOS:000072775900075 PM 9507025 ER PT J AU Wang, LJ Voloshin, ON Stasiak, A Stasiak, A Camerini-Otero, RD AF Wang, LJ Voloshin, ON Stasiak, A Stasiak, A Camerini-Otero, RD TI Homologous DNA pairing domain peptides of RecA protein: Intrinsic propensity to form beta-structures and filaments SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE RecA protein; peptide CD; coil-to-beta transition; DNA-protein interaction; DNA-binding peptides ID SINGLE-STRANDED-DNA; SECONDARY-STRUCTURE; AMINO-ACIDS; COMPLEXES; BINDING; RECOMBINATION; AGGREGATION; L2 AB The 20 amino acid residue peptides derived from RecA loop L2 have been shown to be the pairing domain of RecA. The peptides bind to ss- and dsDNA, unstack ssDNA, and pair the ssDNA to its homologous target in a duplex DNA. As shown by circular dichroism, upon binding to DNA the disordered peptides adopt a beta-structure conformation. Here we show that the conformational change of the peptide from random coil to beta-structure is important in binding ss- and dsDNA. The beta-structure in the DNA pairing peptides can be induced by many environmental conditions such as high pH, high concentration, and non-micellar sodium dodecyl sulfate (6 mM). This behavior indicates an intrinsic property of these peptides to form a beta-structure. A beta-structure model for the loop L2 of RecA protein when bound to DNA is thus proposed. The fact that aromatic residues at the central position 203 strongly modulate the peptide binding to DNA and subsequent biochemical activities can be accounted for by the direct effect of the aromatic amino acids on the peptide conformational change. The DNA-pairing domain of RecA visualized by electron microscopy self-assembles into a filamentous structure Like RecA. The relevance of such a peptide filamentous structure to the structure of RecA when bound to DNA is discussed. (C) 1998 Academic Press Limited. C1 NIH, Genet & Biochem Branch, Bethesda, MD 20892 USA. Univ Lausanne, Lab Analyse Ultrastruct, CH-1015 Lausanne, Switzerland. RP Camerini-Otero, RD (reprint author), NIH, Genet & Biochem Branch, Bldg 10,Rm 9D20, Bethesda, MD 20892 USA. RI Stasiak, Andrzej/E-5551-2010; OI Stasiak, Andrzej/0000-0002-0398-1989 NR 31 TC 23 Z9 23 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAR 20 PY 1998 VL 277 IS 1 BP 1 EP 11 DI 10.1006/jmbi.1997.1591 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZF961 UT WOS:000072950600001 PM 9514744 ER PT J AU Post, RM L'Herrou, T Luckenbaugh, DA Frye, MA Leverich, GS Mikalauskas, K AF Post, RM L'Herrou, T Luckenbaugh, DA Frye, MA Leverich, GS Mikalauskas, K TI Statistical approaches to trial durations in episodic affective illness SO PSYCHIATRY RESEARCH LA English DT Article DE bipolar disorder; statistics; research design; psychopharmacology ID LITHIUM-CARBONATE; BIPOLAR DISORDER; CLINICAL-TRIALS; WORKSHOP REPORT; RECURRENCE; DEPRESSION; PLACEBO; DESIGNS AB In light of the high variability in illness characteristics and patterns among patients with bipolar illness, parallel group designs present severe methodologic difficulties. Crossover, off-on-off-on (B-A-B-A), and other individualized designs may be a useful substitute, but no consensus exists about how to estimate the individual trial durations required in these instances. Several methods for determining optimum trial lengths in crossover designs are presented, illustrated, and discussed. These include: chi-square (chi(2)) for th, expected versus observed number of either episodes or days well; exceeding two standard deviations for average duration of episodes or euthymic intervals; or the Sequential probability Ratio Test (SPRT), which detects when mean values differ from prior statistical expectations. Each method was applied to three demonstration cases using data from actual clinical trials of three patients with different patterns of recurrent affective illness. Each method detected changes in illness severity, although different tests appeared to be sensitive to differing cycle patterns in the patients illustrated. We suggest that these types of analyses and others can be used as indicator statistics to augment global impressions and clinical judgment, and to assist in determining individualized trial durations, both in formal clinical trials and in clinical treatment settings. Once individual responsivity is confirmed with an appropriate interplay of trial design and statistical analysis, the percentage response in a given population can then be compared to other agents or in other populations. Moreover, meta-analytic techniques based on addition of z scores from individuals' effect sizes can then be used to assess overall significance of a drug effect in a given population or subpopulation. The need for further development of appropriate and alternate study designs and analysis methods for bipolar illness is highlighted. Approaches to estimating required trial durations in individuals with different cycle frequencies in crossover and B-A-B-A designs constitute one element of that exploration. (C) 1998 Elsevier Science Ireland Ltd. C1 NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. Elect Village Syst, Centreville, VA USA. RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, NIH, Bldg 10,Room 3N212,10 Ctr Dr,MSC 1272, Bethesda, MD 20892 USA. NR 39 TC 18 Z9 18 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD MAR 20 PY 1998 VL 78 IS 1-2 BP 71 EP 87 DI 10.1016/S0165-1781(97)00144-3 PG 17 WC Psychiatry SC Psychiatry GA ZF283 UT WOS:000072882000008 PM 9579704 ER PT J AU Vahava, O Morell, R Lynch, ED Weiss, S Kagan, ME Ahituv, N Morrow, JE Lee, MK Skvorak, AB Morton, CC Blumenfeld, A Frydman, M Friedman, TB King, MC Avraham, KB AF Vahava, O Morell, R Lynch, ED Weiss, S Kagan, ME Ahituv, N Morrow, JE Lee, MK Skvorak, AB Morton, CC Blumenfeld, A Frydman, M Friedman, TB King, MC Avraham, KB TI Mutation in transcription factor POU4F3 associated with inherited progressive hearing loss in humans SO SCIENCE LA English DT Article ID DNA-BINDING; DOMAIN FACTORS; BRN-3 FAMILY; DEAFNESS; MOUSE; CELLS; SPECIFICITY; RECOGNITION; SUBSETS; NEURONS AB The molecular basis for autosomal dominant progressive nonsyndromic hearing loss in an Israeli Jewish family, Family H, has been determined. Linkage analysis placed this deafness locus, DFNA15, on chromosome 5q31, The human homolog of mouse Pou4f3, a member of the POU-domain family of transcription factors whose targeted inactivation causes profound deafness in mice, was physically mapped to the 25-centimorgan DFNA15-linked region. An 8-base pair deletion in the POU homeodomain of human POU4F3 was identified in Family H. A truncated protein presumably impairs high-affinity binding of this transcription factor in a dominant negative fashion, leading to progressive hearing loss. C1 Tel Aviv Univ, Sackler Sch Med, Dept Human Genet, IL-69978 Tel Aviv, Israel. NIDCD, NIH, Bethesda, MD 20850 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Genet, Seattle, WA 98195 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Hadassah Univ Hosp, Unit Dev Mol Biol & Genet Engn, IL-91240 Jerusalem, Israel. Chaim Sheba Med Ctr, Genet Inst, IL-52621 Tel Hashomer, Israel. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Avraham, KB (reprint author), Tel Aviv Univ, Sackler Sch Med, Dept Human Genet, IL-69978 Tel Aviv, Israel. OI Morell, Robert/0000-0003-1537-7356; Ahituv, Nadav/0000-0002-7434-8144 FU NIDCD NIH HHS [R01 DC01076, Z01 DC 00039] NR 36 TC 201 Z9 214 U1 2 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAR 20 PY 1998 VL 279 IS 5358 BP 1950 EP 1954 DI 10.1126/science.279.5358.1950 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZC748 UT WOS:000072613300050 PM 9506947 ER PT J AU Lin, AY Nutman, TB Kaslow, D Mulvihill, JJ Fontaine, L White, BJ Knutsen, T Theil, KS Raghuprasad, PK Goldstein, AM Tucker, MA AF Lin, AY Nutman, TB Kaslow, D Mulvihill, JJ Fontaine, L White, BJ Knutsen, T Theil, KS Raghuprasad, PK Goldstein, AM Tucker, MA TI Familial eosinophilia: Clinical and laboratory results on a US kindred SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE familial eosinophilia (FE); hypereosinophilic syndrome (HES) ID IDIOPATHIC HYPEREOSINOPHILIC SYNDROME; INTERLEUKIN-5; TRANSLOCATION; FILARIASIS; LEUKEMIA; DISEASE AB We describe a five-generation kindred with familial eosinophilia (FE; MIM131400), characterized by the occurrence of sustained eosinophilia of unidentifiable cause in multiple relatives. The inheritance pattern is consistent with an autosomal dominant pattern. Among 52 related subjects studied, 19 were affected and 33 were unaffected. Ten unaffected spouses were also evaluated. Four subjects with sustained eosinophilia were diagnosed with cardiac abnormalities and two of them also had neurologic symptoms. In comparison with the unaffected or spouses, evaluation of complete blood counts showed that the affected relatives had, as expected, significantly higher white cell (P < 0.005) and absolute eosinophil counts (P < 0.001) and lower red cell counts (P < 0.05). Evaluation of serum cytokine levels (IL-5, IL-3, and granulocyte-macrophage colony-stimulating factor (GMCSF) and serology for parasitic helminth infection demonstrated no differences between the affected and unaffected individuals; no individuals studied had serologic evidence for parasitic infection. There were also no differences in anti-nuclear antibody, serum cobalamin (vitamin B-12) level, immunoglobulin level, leukocyte alkaline phosphatase, rheumatoid factor, HLA analysis, and stool findings for ova and parasites. Among eight affected persons who had peripheral blood or bone marrow karyotype analysis, two carried the same chromosome abnormality, a pericentric inversion of chromosome 10, inv (10) (p11.2q21.2). A gene mapping study is currently underway to study the underlying genetic mechanism(s) of this syndrome. (C) 1998 Wiley-Liss, Inc. C1 NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. NCI, Med Branch, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Santa Clara Valley Med Ctr, Dept Med, Div Hematol Oncol, San Jose, CA 95128 USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. Westat Inc, Rockville, MD USA. Corning Nichols Inst, Dept Cytogenet, San Juan Capistrano, CA USA. Ohio State Univ, Dept Pathol, Div Cytogenet, Med Ctr, Columbus, OH 43210 USA. Ctr Asthma & Allergy, Odessa, TX USA. RP Lin, AY (reprint author), NCI, Genet Epidemiol Branch, EPN 439, Bethesda, MD 20892 USA. RI Tucker, Margaret/B-4297-2015 NR 37 TC 21 Z9 21 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAR 19 PY 1998 VL 76 IS 3 BP 229 EP 237 DI 10.1002/(SICI)1096-8628(19980319)76:3<229::AID-AJMG6>3.0.CO;2-L PG 9 WC Genetics & Heredity SC Genetics & Heredity GA YZ795 UT WOS:000072292400006 PM 9508242 ER PT J AU Marchuk, DA Guttmacher, AE Penner, JA Ganguly, P AF Marchuk, DA Guttmacher, AE Penner, JA Ganguly, P TI Report on the Workshop on Hereditary Hemorrhagic Telangiectasia, July 10-11, 1997 SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Editorial Material C1 Duke Univ, Med Ctr, Dept Genet, Durham, NC 27710 USA. Univ Vermont, Coll Med, Dept Pediat, Burlington, VT USA. Univ Vermont, Coll Med, Dept Med, Burlington, VT USA. Michigan State Univ, Dept Med, E Lansing, MI 48824 USA. NHLBI, Thrombosis & Hemostasis Sci Res Grp, NIH, Bethesda, MD 20892 USA. RP Marchuk, DA (reprint author), Duke Univ, Med Ctr, Dept Genet, Box 3175, Durham, NC 27710 USA. NR 0 TC 25 Z9 25 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAR 19 PY 1998 VL 76 IS 3 BP 269 EP 273 DI 10.1002/(SICI)1096-8628(19980319)76:3<269::AID-AJMG12>3.0.CO;2-F PG 5 WC Genetics & Heredity SC Genetics & Heredity GA YZ795 UT WOS:000072292400012 PM 9508248 ER PT J AU Whelton, PK Appel, LJ Espeland, MA Applegate, WB Ettinger, WH Kostis, JB Kumanyika, S Lacy, CR Johnson, KC Folmar, S Cutler, JA AF Whelton, PK Appel, LJ Espeland, MA Applegate, WB Ettinger, WH Kostis, JB Kumanyika, S Lacy, CR Johnson, KC Folmar, S Cutler, JA CA TONE Collaborative Res Grp TI Sodium reduction and weight loss in the treatment of hypertension in older persons - A randomized controlled trial of nonpharmacologic interventions in the elderly (TONE) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORONARY HEART-DISEASE; BLOOD-PRESSURE; MILD HYPERTENSION; RISK; THERAPY; WOMEN; MASS AB Context.-Nonpharmacologic interventions are frequently recommended for treatment of hypertension in the elderly, but there is a paucity of evidence from randomized controlled trials in support of this recommendation. Objective.-To determine whether weight loss or reduced sodium intake is effective in the treatment of older persons with hypertension. Design.-Randomized controlled trial. Participants.-A total of 875 men and women aged 60 to 80 years with systolic blood pressure lower than 145 mm Hg and diastolic blood pressure lower than 85 mm Hg while receiving treatment with a single antihypertensive medication. Setting.-Four academic health centers. Intervention.-The 585 obese participants were randomized to reduced sodium intake, weight loss, both, or usual care, and the 390 nonobese participants were randomized to reduced sodium intake or usual care, Withdrawal of antihypertensive medication was attempted after 3 months of intervention. Main Outcome Measure.-Diagnosis of high blood pressure at 1 or more follow-up visits, or treatment with antihypertensive medication, or a cardiovascular event during follow-up (range, 15-36 months; median, 29 months). Results.-The combined outcome measure was less frequent among those assigned vs not assigned to reduced sodium intake (relative hazard ratio, 0.69; 95% confidence interval [CI], 0.59-0.81; P<.001) and, in obese participants, among those assigned vs not assigned to weight loss (relative hazard ratio, 0.70; 95% CI, 0.57-0.87; P<.001). Relative to usual care, hazard ratios among the obese participants were 0.60 (95% CI, 0.45-0.80; P<.001) for reduced sodium intake alone, 0.64 (95% CI, 0.49-0.85; P=.002) for weight loss alone, and 0.47 (95% CI, 0.35-0.64; P<.001) for reduced sodium intake and weight loss combined. The frequency of cardiovascular events during follow-up was similar in each of the 6 treatment groups. Conclusion.-Reduced sodium intake and weight loss constitute a feasible, effective, and safe nonpharmacologic therapy of hypertension in older persons. C1 Tulane Univ, Sch Publ Hlth & Trop Med, Off Dean, Dept Biostat & Epidemiol, New Orleans, LA 70112 USA. Johns Hopkins Univ, Sch Med, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. Wake Forest Univ, Sch Med, Dept Internal Med, Winston Salem, NC 27109 USA. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Div Cardiovasc Dis & Hypertens, New Brunswick, NJ USA. Penn State Univ, Coll Med, Ctr Biostat & Epidemiol, Hershey, PA 17033 USA. NHLBI, Clin Applicat & Prevent Program, NIH, Bethesda, MD 20892 USA. RP Whelton, PK (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, Off Dean, Dept Biostat & Epidemiol, 17th Floor,1501 Canal St, New Orleans, LA 70112 USA. EM PWHELTON@TULANE.EDU FU NHLBI NIH HHS [R01 HL-48642]; NIA NIH HHS [R01 AG-09771, R01 AG-09799] NR 37 TC 609 Z9 620 U1 2 U2 32 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 18 PY 1998 VL 279 IS 11 BP 839 EP 846 DI 10.1001/jama.279.11.839 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA ZA943 UT WOS:000072417600030 PM 9515998 ER PT J AU Martin, A AF Martin, A TI Cortical representation of category-specific knowledge SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NIMH, Lab Brain Cognit, Bethesda, MD 20892 USA. RI martin, alex/B-6176-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD MAR 18 PY 1998 VL 10 SU S BP 12 EP 12 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA ZJ263 UT WOS:000073196500027 ER PT J AU Grant, SJ Bonson, KR Matochik, JA Contoreggi, C London, ED AF Grant, SJ Bonson, KR Matochik, JA Contoreggi, C London, ED TI A brain imaging study of induced craving for cocaine using positron emission tomography. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NIDA, Brain Imaging Ctr, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD MAR 18 PY 1998 VL 10 SU S BP 65 EP 65 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA ZJ263 UT WOS:000073196500187 ER PT J AU Ernst, M Jons, PH Matochik, JA Van Horn, JD Heishman, SJ London, ED AF Ernst, M Jons, PH Matochik, JA Van Horn, JD Heishman, SJ London, ED TI Nicotine withdrawal and cerebral blood flow during a working memory task SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NIDA, Brain Imaging Ctr, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD MAR 18 PY 1998 VL 10 SU S BP 82 EP 82 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA ZJ263 UT WOS:000073196500237 ER PT J AU Marks, AR Wild, K Grafman, J Higgins, J Massaquoi, S AF Marks, AR Wild, K Grafman, J Higgins, J Massaquoi, S TI Dissociating errors and reaction time on the serial reaction time task: The performance of patients with frontal-lobe lesions and patients with cerebellar atrophy SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD MAR 18 PY 1998 VL 10 SU S BP 93 EP 93 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA ZJ263 UT WOS:000073196500270 ER PT J AU Otterson, GA Xiao, GH Geradts, J Jin, F Chen, WD Niklinska, W Kaye, FJ Yeung, RS AF Otterson, GA Xiao, GH Geradts, J Jin, F Chen, WD Niklinska, W Kaye, FJ Yeung, RS TI Protein expression and functional analysis of the FHIT gene in human tumor cells SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID 3P14.2 FRAGILE SITE; LUNG-CANCER; CARCINOMA; IDENTIFICATION; BREAKPOINTS; SUPPRESSOR; LINES AB Background: The fragile histidine triad (FHIT) gene at chromosome 3p14.2 has been proposed to be a candidate tumor suppressor gene in human cancers, To test whether FHIT exhibits the functional properties of a tumor suppressor gene, we studied the expression of its protein (pFHIT) in human carcinoma cells and examined the ability of FHIT to inhibit the neoplastic phenotype of cancer cells, Methods: Subcellular localization and patterns of protein expression in tumor cells were determined by immunohistochemical analysis and immunoblotting with the use of polyclonal anti-pFHIT antisera, In tumor cells with undetectable pFHIT, we examined the effect of recombinant pFHIT expression on morphology, growth rate, colony formation, and in vivo tumor formation, Results: We demonstrated that pFHIT is a cytoplasmic 17-kd polypeptide whose expression could not be detected in 30 of 52 human carcinoma cell lines tested, We observed, however, that the stable overexpression of pFHIT did not alter cell morphology, inhibit colony formation, or inhibit cell proliferation in vitro, Furthermore, overexpression of pFHIT did not lead to altered cell cycle kinetics in dividing cells, The in vivo tumorigenicity of a tumor cell line that expressed high levels of recombinant pFHIT was equivalent to that of control transfectants and of parental cells, Conclusions: These results suggest that the replacement of pFHIT in human carcinoma cells does not suppress tumor cell growth and that this protein may be involved in tumorigenesis in ways that are distinct from the "classic" tumor suppressor paradigm. C1 NCI, Div Clin Sci, Med Branch, Bethesda, MD 20892 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ N Carolina, Sch Med, Dept Pathol, Chapel Hill, NC USA. RP Kaye, FJ (reprint author), NIH, Natl Naval Med Ctr, Bldg 8,Rm 5101, Bethesda, MD 20889 USA. EM fkaye@helix.nih.gov RI kaye, frederic/E-2437-2011; CHEN, WEI-DONG/F-4521-2014 OI CHEN, WEI-DONG/0000-0003-2264-5515 FU NCI NIH HHS [CA06927, CA61889] NR 30 TC 76 Z9 84 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 18 PY 1998 VL 90 IS 6 BP 426 EP 432 DI 10.1093/jnci/90.6.426 PG 7 WC Oncology SC Oncology GA ZC533 UT WOS:000072589900008 PM 9521166 ER PT J AU Heinonen, OP Albanes, D Virtamo, J Taylor, PR Huttunen, JK Hartman, AM Haapakoski, J Malila, N Rautalahti, M Ripatti, S Maenpaa, H Teerenhovi, L Koss, L Virolainen, M Edwards, BK AF Heinonen, OP Albanes, D Virtamo, J Taylor, PR Huttunen, JK Hartman, AM Haapakoski, J Malila, N Rautalahti, M Ripatti, S Maenpaa, H Teerenhovi, L Koss, L Virolainen, M Edwards, BK TI Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: Incidence and mortality in a controlled trial SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SERUM VITAMIN-A; FOLLOW-UP; RISK-FACTORS; LUNG-CANCER; RETINOL; PREVENTION; CARCINOMA; DIET; EPIDEMIOLOGY; PLASMA AB Background: Epidemiologic studies ha,le suggested that vitamin E and beta-carotene may each influence the development of prostate cancer, In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a controlled trial, we studied the effect of alpha-tocopherol (a form of vitamin E) and beta-carotene supplementation, separately or together, on prostate cancer in male smokers, Methods: A total of 29133 male smokers aged 50-69 years from southwestern Finland were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or placebo daily for 5-8 Sears (median, 6.1 years), The supplementation effects were estimated by a proportional hazards model, and two-sided P values were calculated, Results: We found 246 new cases of and 62. deaths from prostate cancer during the follow-up period, A 32% decrease (95% confidence interval [CI] = -47% to -12%) in the incidence of prostate cancer was observed among the subjects receiving alpha-tocopherol (n = 14564) compared with those not receiving it (n = 14569), The reduction was evident in clinical prostate cancer but not in latent cancer, Mortality from prostate cancer was 41% lower (95% CI = -65% to -1%) among men receiving alpha-tocopherol. Among subjects receiving beta-carotene (n = 14560), prostate cancer incidence was 23% higher (95% CI = -4%-59%) and mortality was 15% higher (95% CI = -30%-89%) compared with those not receiving it (n = 14 573), Neither agent had any effect on the time interval between diagnosis and death, Conclusions: Long-term supplementation with alpha-tocopherol substantially reduced prostate cancer incidence and mortality in male smokers, Other controlled trials are required to confirm the findings. C1 Univ Helsinki, Dept Publ Hlth, FIN-00014 Helsinki, Finland. NCI, Canc Prevent Studies Branch, Div Clin Sci, Bethesda, MD 20892 USA. NCI, Canc Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Natl Publ Hlth Inst, Helsinki, Finland. Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland. Montefiore Med Ctr, Bronx, NY 10467 USA. RP Heinonen, OP (reprint author), Univ Helsinki, Dept Publ Hlth, POB 41, FIN-00014 Helsinki, Finland. RI Albanes, Demetrius/B-9749-2015; Ripatti, Samuli/H-9446-2014 OI Ripatti, Samuli/0000-0002-0504-1202 FU NCI NIH HHS [N01CN45165] NR 43 TC 593 Z9 611 U1 1 U2 31 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 18 PY 1998 VL 90 IS 6 BP 440 EP 446 DI 10.1093/jnci/90.6.440 PG 7 WC Oncology SC Oncology GA ZC533 UT WOS:000072589900010 PM 9521168 ER PT J AU Hayes, RB Linet, M Dosemeci, M Yin, SN AF Hayes, RB Linet, M Dosemeci, M Yin, SN TI Benzene and the dose-related incidence of hematologic neoplasms in China - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID EXPOSURES; WORKERS C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Chinese Acad Prevent Med, Beijing, Peoples R China. RP Hayes, RB (reprint author), NIH, Execut Plaza N,Suite 418, Bethesda, MD 20892 USA. NR 8 TC 2 Z9 2 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 18 PY 1998 VL 90 IS 6 BP 470 EP 471 PG 2 WC Oncology SC Oncology GA ZC533 UT WOS:000072589900020 ER PT J AU Blagosklonny, MV Iglesias, A Zhan, ZR Fojo, T AF Blagosklonny, MV Iglesias, A Zhan, ZR Fojo, T TI Like p53, the proliferation-associated protein p120 accumulates in human cancer cells following exposure to anticancer drugs SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CELLULAR TUMOR-ANTIGEN; NUCLEOLAR ANTIGEN; DNA-DAMAGE; EXPRESSION; GROWTH; INHIBITION AB Accumulation of p53 protein following DNA damage is independent of transcription; in turn, p53 transcriptionally induces other proteins, Herein we demonstrated that p120, a proliferation-associated protein, was induced by DNA-damaging and microtubule-active drugs in human cancer cells, However, induction of p120 was independent of p53; and expression of exogenous wt p53 induced p21(WAF1/CIP1) ut not p120, excluding p120 as a transcriptional target of p53, Like p53, induction of p120 by anticancer drugs did not require transcription, Induction of p120 by actinomycin-D occured at concentrations which inhibit RNA synthesis and p120 mRNA levels, Inhibition of proteasomes resulted in accumulation of higher molecular weight proteins, reacting with anti-p120 antibodies, This suggests that the mechanisms of p120 and p53 induction are similar and involve inhibition of degradation, p120 protein stabilization represents an expedient means for accumulation of key response proteins following exposure to cytotoxic agents. (C) 1998 Academic Press. C1 NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Blagosklonny, MV (reprint author), NCI, Med Branch, NIH, Bldg 10,Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 21 TC 12 Z9 13 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 17 PY 1998 VL 244 IS 2 BP 368 EP 373 DI 10.1006/bbrc.1998.8278 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZF275 UT WOS:000072881200010 PM 9514935 ER PT J AU Xiao, H Neuveut, C Benkirane, M Jeang, KT AF Xiao, H Neuveut, C Benkirane, M Jeang, KT TI Interaction of the second coding exon of Tat with human EF-1 delta delineates a mechanism for HIV-1-mediated shut-off of host mRNA translation SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TRANS-ACTIVATOR GENE; NUCLEAR-PORES; TYPE-1 DNA; CELL-CYCLE; T-CELLS; PROTEIN; HIV-1; RNA; REPLICATION AB HIV-1 Tat has pleiotropic functions. While its most studied role is to activate transcription from the retroviral long terminal repeat (LTR)-promoter, Tat also has functions as a secretable growth factor, a T-cell activator, and an inducer of cellular apoptosis, amongst others. For its transcriptional function, the first coding exon of Tat appears wholly sufficient; however, lentiviruses (HIVs and SIVs) maintain and conserve a second coding exon for Tat. While the function(s) of the second exon of Tat has remained largely unknown, its integrity in lentiviral genomes suggests biological importance, possibly a role in non-transcriptional activities. To understand better the biology of the second exon of Tat in HIV-1 infection of cells, we have searched for cellular proteins that bind specifically to this protein domain. Here, we report that the human translation elongation factor 1-delta (EF-1 delta) binds to the second exon of HIV-1 Tat. Interaction between Tat and EF-1 delta dramatically reduces the efficiency of the translation of cellular, but not viral, mRNAs. These findings suggest that a non-transcriptional activity of Tat modulates cellular protein synthesis, thereby affecting the metabolism of host cells. (C) 1998 Academic Press. C1 NIAID, Mol Microbiol Lab, Mol Virol Sect, NIH, Bethesda, MD 20892 USA. RP Xiao, H (reprint author), NIAID, Mol Microbiol Lab, Mol Virol Sect, NIH, Bldg 4,Room 306, Bethesda, MD 20892 USA. EM hxiao@atlas.niaid.nih.gov RI Jeang, Kuan-Teh/A-2424-2008 NR 35 TC 41 Z9 41 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 17 PY 1998 VL 244 IS 2 BP 384 EP 389 DI 10.1006/bbrc.1998.8274 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZF275 UT WOS:000072881200013 PM 9514931 ER PT J AU Jourd'heuil, D Mai, CT Laroux, FS Wink, DA Grisham, MB AF Jourd'heuil, D Mai, CT Laroux, FS Wink, DA Grisham, MB TI The reaction of S-nitrosoglutathione with superoxide SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE nitrosothiols; superoxide; nitric oxide; peroxynitrite; dinitrogen tretroxide; glutathione; nitrosoglutathione; superoxide dismutase; dihydrorhodamine; 2,3-diaminonaphthalene ID NITRIC-OXIDE; NITROSO-GLUTATHIONE; PLATELET ACTIVATION; INHIBITION; OXIDATION; INVITRO AB The nitric oxide (NO)-dependent S-nitrosation of thiols to generate S-nitrosothiols has been proposed as an important pathway for the metabolism of NO in vivo, Although it has been suggested that these S-nitrosated compounds are resistant to decomposition by reactive oxygen metabolites (ROMs), very little information is available regarding the interaction between S-nitrosothiols and ROMs. We found that S-nitrosoglutathione (GSNO) rapidly reacted with O-2(-) to generate glutathione disulfide and equimolar quantities of nitrite and nitrate, The reaction was second order with respect of GSNO and first order with respect of O-2(-) with a rate equation of -d[GSNO]/dt = 2k(3)[GSNO](2)[O-2(-)], where k(3) = 3 - 6x10(8) M(-2)s(-1), I, addition, the reaction of GSNO with O-2(-) generated a strong oxidant as an intermediate capable of oxidizing dihydrorhodamine in the absence of the apparent generation of NO, We conclude that O-2(-) may act as a physiological modulator of S-nitrosation reactions by directly promoting the decomposition of S-nitrosothiols. (C) 1998 Academic Press. C1 Louisiana State Univ, Med Ctr, Dept Cellular & Mol Physiol, Shreveport, LA 71130 USA. NCI, Bethesda, MD 20892 USA. RP Jourd'heuil, D (reprint author), Louisiana State Univ, Med Ctr, Dept Cellular & Mol Physiol, Shreveport, LA 71130 USA. FU NIDDK NIH HHS [DK 43785] NR 26 TC 29 Z9 31 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 17 PY 1998 VL 244 IS 2 BP 525 EP 530 DI 10.1006/bbrc.1998.8227 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZF275 UT WOS:000072881200036 PM 9514894 ER PT J AU Misawa, H Ohtsubo, M Copeland, NG Gilbert, DJ Jenkins, NA Yoshimura, A AF Misawa, H Ohtsubo, M Copeland, NG Gilbert, DJ Jenkins, NA Yoshimura, A TI Cloning and characterization of a novel class II phosphoinositide 3-kinase containing C2 domain SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HUMAN PHOSPHATIDYLINOSITOL 3-KINASE; ERYTHROPOIETIN RECEPTOR; SIGNAL-TRANSDUCTION; PROTEIN; KINASE; FAMILY; EXPRESSION; SEQUENCES; SUBUNITS; SYSTEM AB Phosphoinositide 3-kinases (PI3Ks) have been shown to play critical roles in cell growth, differentiation, survival, and vesicular transport. Class II PI3Ks have been recently identified in mouse and human (PI3K-C2 alpha/m-p170/m-cpk and HsC2-PI3K) and in Drosophila (PI3K_68D/cpk) which contain C2 domain at the C-terminus, However, their physiological function is largely unknown. We report here cloning and characterization of murine PI3K-C2 gamma, a novel class II PI3K. The catalytic domain as well as C2 domain are highly conserved in the Class II PI3K family, while the N-terminal regions of these proteins share little similarity. Unlike other Class II PI3Ks, PI3K-C2 gamma exclusively expressed in the liver, and a N-terminal truncated form was found in lung and a certain hematopoietic cell line. Specific antiserum against PI3K-C2 gamma precipitated PI3K activity from the membrane fraction of mouse liver but not from heart. Recombinant PI3K-C2 gamma exhibited a restricted lipid substrate specificity; it phosphorylated phosphatidylinositol (PtdIns) and PtdIns4P but not PtdIns(4,5)P-2. Deletion mutations revealed that both the N-terminal region and the C2 domain were critical for enzymatic activity. The murine PI3K-C2 gamma gene locus was mapped to the distal region of mouse chromosome 6 in a region of homology with human chromosome 12p, which is distinct from the position of HsC2-PI3K. Cloning and biochemical characterization of the third member of class II PI3Ks provide a new insight into the function of this subfamily of PI3Ks. (C) 1998 Academic Press. C1 Kurume Univ, Inst Life Sci, Kurume, Fukuoka 839, Japan. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Yoshimura, A (reprint author), Kurume Univ, Inst Life Sci, Aikawamachi 2432-3, Kurume, Fukuoka 839, Japan. RI Yoshimura, Akihiko/K-5515-2013 NR 41 TC 48 Z9 51 U1 0 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 17 PY 1998 VL 244 IS 2 BP 531 EP 539 DI 10.1006/bbrc.1998.8294 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZF275 UT WOS:000072881200037 PM 9514948 ER PT J AU Fortini, P Pascucci, B Parlanti, E Sobol, RW Wilson, SH Dogliotti, E AF Fortini, P Pascucci, B Parlanti, E Sobol, RW Wilson, SH Dogliotti, E TI Different DNA polymerases are involved in the short- and long-patch base excision repair in mammalian cells SO BIOCHEMISTRY LA English DT Article ID YEAST SACCHAROMYCES-CEREVISIAE; BOVINE TESTIS; LIGASE-I; BETA; REPLICATION; RECONSTITUTION; PURIFICATION; EXTRACTS; RESIDUES; PATHWAY AB Mammalian cells possess two distinct pathways for completion of base excision repair (BER): the DNA polymerase beta (Pol beta)-dependent short-patch pathway (replacement of one nucleotide), which is the main route, and the long-patch pathway (resynthesis of 2-6 nucleotides), which is PCNA-dependent. To address the issue of how these two pathways share their role in BER the ability of Pol beta-defective mammalian cell extracts to repair a single abasic site constructed in a circular duplex plasmid molecule was tested in a standard in vitro repair reaction. Pol beta-deficient extracts were able to perform both BER pathways. However, in the case of the short-patch BER, the repair kinetics was significantly slower than with Pol beta-proficient extracts, while the efficiency of the long-patch synthesis was unaffected by the loss of Pol beta. The repair synthesis was fully dependent on PCNA for the replacement of long patches. These data give the first evidence that in cell extracts DNA polymerases other than Pol beta are specifically involved in the long-patch BER. These DNA polymerases are also able to perform short patch BER in the absence of PCNA, although less efficiently than Pol beta. These findings lead to a novel model whereby the two BER pathways are characterized by different protein requirements, and a functional redundancy at the level of DNA polymerases provides cells with backup systems. C1 Ist Super Sanita, Comparat Toxicol & Ecotoxicol Lab, I-00161 Rome, Italy. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Dogliotti, E (reprint author), Ist Super Sanita, Comparat Toxicol & Ecotoxicol Lab, Viale Regina Elena 299, I-00161 Rome, Italy. EM dogliott@net.iss.it RI Sobol, Robert/E-4125-2013 OI Sobol, Robert/0000-0001-7385-3563 NR 29 TC 168 Z9 174 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 17 PY 1998 VL 37 IS 11 BP 3575 EP 3580 DI 10.1021/bi972999h PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZE116 UT WOS:000072759300001 PM 9530283 ER PT J AU Lee, CGL Gottesman, MM Cardarelli, CO Ramachandra, M Jeang, KT Ambudkar, SV Pastan, I Dey, S AF Lee, CGL Gottesman, MM Cardarelli, CO Ramachandra, M Jeang, KT Ambudkar, SV Pastan, I Dey, S TI HIV-1 protease inhibitors are substrates for the MDR1 multidrug transporter SO BIOCHEMISTRY LA English DT Article ID P-GLYCOPROTEIN INHIBITORS; BLOOD-BRAIN-BARRIER; IN-VIVO; INSECT CELLS; T-CELLS; RESISTANCE; EXPRESSION; TISSUES; GENE; INFECTION AB The FDA approved HIV-1 protease inhibitors, ritonavir, saquinavir, and indinavir, are very effective in inhibiting HIV-1 replication, but their long-term efficacy is unknown. Since in vivo efficacy depends on access of these drugs to intracellular sites where HIV-1 replicates, we determined whether these protease inhibitors are recognized by the MDR1 multidrug transporter (P-glycoprotein, or P-gp), thereby reducing their intracellular accumulation. In vitro studies in isolated membrane preparations from insect cells infected with MDR1-expressing recombinant baculovirus showed that these inhibitors significantly stimulated P-gp-specific ATPase activity and that this stimulation was inhibited by SDZ PSC 833, a potent inhibitor of P-gp. Furthermore, photoaffinity labeling of P-gp with the substrate analogue [I-125]iodoarylazidoprazosin (IAAP) was inhibited by all three inhibitors. Cell-based approaches to evaluate the ability of these protease inhibitors to compete for transport of known P-gp substrates showed that all three HIV-1 protease inhibitors were capable of inhibiting the transport of some of the known P-gp substrates but their effects were generally weaker than other documented P-gp modulators such as verapamil or cyclosporin A. Inhibition of HIV-1 replication by all three protease inhibitors was reduced but could be restored by MDR1 inhibitors in cells expressing MDR1. These results indicate that the HIV-1 protease inhibitors are substrates of the human multidrug transporter, suggesting that cells in patients that express the MDR1 transporter will be relatively resistant to the anti-viral effects of the HIV-1 protease inhibitors, and that absorption, excretion, and distribution of these inhibitors in the body may be affected by the multidrug transporter. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 1A09,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. EM mgottesman@nih.gov RI Ambudkar, Suresh/B-5964-2008; Jeang, Kuan-Teh/A-2424-2008 NR 54 TC 406 Z9 415 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 17 PY 1998 VL 37 IS 11 BP 3594 EP 3601 DI 10.1021/bi972709x PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZE116 UT WOS:000072759300004 PM 9530286 ER PT J AU Pommier, Y Kohlhagen, G Wu, CX Simmons, DT AF Pommier, Y Kohlhagen, G Wu, CX Simmons, DT TI Mammalian DNA topoisomerase I activity and poisoning by camptothecin are inhibited by simian virus 40 large T antigen SO BIOCHEMISTRY LA English DT Article ID REPLICATION PROTEIN-A; LARGE-TUMOR-ANTIGEN; POLYMERASE-ALPHA-PRIMASE; SV40 DNA; VIRAL ORIGIN; HELICASE; INITIATION; IDENTIFICATION; TRANSCRIPTION; CLEAVAGE AB DNA topoisomerase I (top1) is a ubiquitous enzyme that forms reversible DNA single-strand breaks (cleavage complexes) and plays a role in transcription, DNA replication, and repair. Top1 is the target of camptothecins which selectively trap top1 cleavage complexes and represent a novel class of anticancer drugs active against human solid tumors,, The present study demonstrates that recombinant large T antigen (T-Ag), a virus encoded helicase with strong affinity for tumor suppressors and cell cycle- and replication-related proteins, suppresses top1 cleavage complexes and top1 catalytic activity. This top1 suppressive activity is probably not due to T-Ag binding to DNA, as a T-Ag truncation mutant containing only the first 246 amino acids and deficient in DNA binding also inhibited top1, and the inhibition was independent of ATP. T-Ag also antagonized and reversed the trapping of top1 cleavage complexes by camptothecin, These results demonstrate a functional interaction between T-Ag and top1: they also suggest the importance of top1-protein interactions for the regulation of DNA replication and modulation of camptothecin activity. C1 NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Univ Delaware, Dept Biol Sci, Newark, DE 19716 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bldg 37,Room 5D02, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA36118] NR 56 TC 26 Z9 26 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 17 PY 1998 VL 37 IS 11 BP 3818 EP 3823 DI 10.1021/bi972067d PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZE116 UT WOS:000072759300027 PM 9521701 ER PT J AU Jaffe, H Veeranna Shetty, KT Pant, HC AF Jaffe, H Veeranna Shetty, KT Pant, HC TI Characterization of the phosphorylation sites of human high molecular weight neurofilament protein by electrospray ionization tandem mass spectrometry and database searching SO BIOCHEMISTRY LA English DT Article ID AMYOTROPHIC LATERAL SCLEROSIS; AMINO-ACID-SEQUENCES; NF-H; SPECTRAL DATA; IDENTIFICATION; PEPTIDES; KINASE; SUBUNIT; DEFICIENCY; ANTIBODIES AB Hyperphosphorylated high molecular weight neurofilament protein (NF-H) exhibits extensive phosphorylation on lysine serine-proline (KSP) repeats in the C-terminal domain of the molecule. Specific phosphorylation sites in human NF-H were identified by proteolytic digestion and analysis of the resulting digests by a combination of microbore liquid chromatography, electrospray ionization tandem (MS/MS) ion trap mass spectrometry, and database searching. The computer programs utilized (PEPSEARCH and SEQUEST) are capable of identifying peptides and phosphorylation sites from uninterpreted MS/MS spectra, and by use of these methods, 27 phosphopeptides and their phosphorylated residues were identified. On the basis of these phosphopeptides, 38 phosphorylation sites in human NF-H were characterized. These include 33 KSP, lysine-threonine-proline (KTP) or arginine-serine proline (RSP) sites and four unphosphorylated sites, all of which occur in the KSP repeat domain (residues 502-823), and one threonine phosphorylation site observed in a KVPTPEK motif. Six KSP sites were not characterized because of the failure to isolate and identify corresponding phosphopeptides, Heterogeneity in serine and threonine phosphorylation was observed at three sites or deduced to occur at three sites on the basis of enzyme specificity. As a result of the phosphorylated motifs identified (KSPEKEE, KSPVKAE, KSPAEAK, KSPPEAK, KSPEAKT, KSPAEVK, and KVPTPEK), human NF-H tail domain is postulated to be a substrate of proline-directed kinases, The threonine-phosphorylated KVPTPEK motif suggested the existence of a novel proline-directed kinase. C1 NINDS, Prot Peptide Sequencing Facil, NIH, Bethesda, MD 20892 USA. NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. Natl Inst Mental Hlth & Neurosci, Bangalore 560029, Karnataka, India. RP Jaffe, H (reprint author), NINDS, Prot Peptide Sequencing Facil, NIH, Bethesda, MD 20892 USA. NR 53 TC 52 Z9 53 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 17 PY 1998 VL 37 IS 11 BP 3931 EP 3940 DI 10.1021/bi972518u PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZE116 UT WOS:000072759300040 PM 9521714 ER PT J AU Gould, AL Rossouw, JE Santanello, NC Heyse, JF Furberg, CD AF Gould, AL Rossouw, JE Santanello, NC Heyse, JF Furberg, CD TI Cholesterol reduction yields clinical benefit - Impact of statin trials SO CIRCULATION LA English DT Article DE cholesterol; meta-analysis; mortality ID CORONARY HEART-DISEASE; PRIMARY-PREVENTION TRIAL; MIDDLE-AGED MEN; ATHEROSCLEROSIS-REGRESSION; CARDIOVASCULAR EVENTS; LOVASTATIN THERAPY; SERUM-CHOLESTEROL; ARTERY DISEASE; MORTALITY; INTERVENTION AB Background-We determined the effect of incorporating the results of eight recently published trials of Hmg CoA reductase inhibitors ("statins") on the conclusions fi-om our previously published meta-analysis regarding the clinical benefit of cholesterol lowering. Methods and Results-We used the same analytic approach as in our previous investigation, separating the specific effects of cholesterol lowering from the effects attributable to the different types of intervention studied, The reductions in coronary heart disease (CHD) and total mortality risk observed for the statins fell near the predictions from our earlier meta-analysis. Including the statin trial findings into the calculations led to a prediction that for every 10 percentage points of cholesterol lowering, CHD mortality risk would be reduced by 15% (P<.001), and total mortality risk would be reduced by 11% (P<.001), as opposed to the values of 13% and 10%, respectively, reported previously. Cholesterol lowering in general and by the statins in particular does not increase non-CHD mortality risk. Conclusions-Adding the results from the statin trials confirmed our original conclusion that lowering cholesterol is clinically beneficial. The relationships (slope) between cholesterol lowering and reduction in CHD and total mortality) risk became stronger, and the standard error of the estimated slopes decreased by about half. Use of statins does not increase non-CHD mortality risk. The effect of the statins on CHD and total mortality risk can be explained by their lipid-lowering ability and appears to be directly proportional to the degree to which they lower lipids. C1 Merck Res Labs, W Point, PA 19486 USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. NIH, Bethesda, MD 20892 USA. RP Gould, AL (reprint author), Merck Res Labs, BL3-2, W Point, PA 19486 USA. EM goulda@merck.com NR 44 TC 294 Z9 306 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 17 PY 1998 VL 97 IS 10 BP 946 EP 952 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ZB649 UT WOS:000072493700002 PM 9529261 ER PT J AU Ajmani, RS Roukoyatkina, N Talan, M Rifkind, JM AF Ajmani, RS Roukoyatkina, N Talan, M Rifkind, JM TI The relationship between cold induced hypertension and Whole Blood Viscosity in rats SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA, Lab Cellular & Mol Biol & Cardiovasc Sci, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 541 BP A93 EP A93 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006400540 ER PT J AU Allison, KC Henkart, PA AF Allison, KC Henkart, PA TI Purification of a factor that enhances phagocytosis of apoptotic cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1662 BP A285 EP A285 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401655 ER PT J AU Biragyn, A Tani, K Grimm, M Weeks, S Kwak, LW AF Biragyn, A Tani, K Grimm, M Weeks, S Kwak, LW TI Chemokine fused single chain lymphoma derived Ig vaccines induce potent protective immunity and CD8(+) effector T cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Dept Exp Transplant & Immunol, SAIC, Ft Detrick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1557 BP A267 EP A267 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401552 ER PT J AU Bivalacqua, TJ Champion, HC Lambert, DG Nass, JA Patterson, ME Pachtman, C Keeffer, LK Kadowitz, PJ AF Bivalacqua, TJ Champion, HC Lambert, DG Nass, JA Patterson, ME Pachtman, C Keeffer, LK Kadowitz, PJ TI Analysis of vasodilator responses to novel nitric oxide donors in the hindlimb vascular bed of the cat. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Tulane Univ, Sch Med, New Orleans, LA 70112 USA. NCI, Frederick, MD 21702 USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 456 BP A79 EP A79 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006400456 ER PT J AU Borrego, F Brooks, A Coligan, JE AF Borrego, F Brooks, A Coligan, JE TI HLA-Cw*0304 recognition by NK cells: Differences between CD94/NKG2 and CD158b. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Mol Struct Lab, NIH, Twinbrook, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3500 BP A603 EP A603 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403495 ER PT J AU Brahmi, Z Chua, HL Gelfanova, V Hommel-Berrey, G Posch, P Coligan, J Brooks, A AF Brahmi, Z Chua, HL Gelfanova, V Hommel-Berrey, G Posch, P Coligan, J Brooks, A TI The transfection of CD94 into YT-Indy leads to the maturation of NKG2A but does not lead to the inhibition of lysis of susceptible target cells expressing different HLA class I antigens. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Immunol Microbiol, Indianapolis, IN 46202 USA. NIAID, Mol Struct Lab, NIH, Bethesda, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3501 BP A603 EP A603 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403498 ER PT J AU Bruce, DS Howard, GE Oeltgen, PR Su, TP AF Bruce, DS Howard, GE Oeltgen, PR Su, TP TI Elucidation of the delta opioid receptor subtype activity of Hibernation-Induction Trigger (HIT). SO FASEB JOURNAL LA English DT Meeting Abstract C1 Wheaton Coll, Dept Biol, Wheaton, IL 60187 USA. Univ Kentucky, Grad Ctr Toxicol, Lexington, KY 40511 USA. NIDA, Neurosci Branch, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 2200 BP A379 EP A379 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006402195 ER PT J AU Chang, JT Shevach, EM Segal, BM AF Chang, JT Shevach, EM Segal, BM TI Induction of Th1 autoimmune effector cells is dependent on IL-12 mediated upregulation of IL-12 receptor beta 2 chain expression SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, LI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1793 BP A307 EP A307 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401788 ER PT J AU Cho, H Takekoshi, K Kehri, J AF Cho, H Takekoshi, K Kehri, J TI A new member of the RGS family, RGS14, impairs MAP and SAP kinase activation mediated via G alpha i and G alpha 13-coupled signaling pathways. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, LIR, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1564 BP A269 EP A269 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401559 ER PT J AU Chung, DH Plaksin, D Hunziker, RD Mage, MG Margulies, DH AF Chung, DH Plaksin, D Hunziker, RD Mage, MG Margulies, DH TI Single chain beta-2 microglobulin-H-2D(d) molecules positively select CD8 cells of broad repertoire when expressed transgenically in beta-2 M knockout mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RI Margulies, David/H-7089-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1779 BP A305 EP A305 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401775 ER PT J AU Connors, M Lopez, JC McNeil, AC Shupert, WL Gea-Banacloche, JC AF Connors, M Lopez, JC McNeil, AC Shupert, WL Gea-Banacloche, JC TI Resistance to HIV - Challenge in SCID mice engrafted with PBL of long term non-progressors is mediated by CD8+ T cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3313 BP A571 EP A571 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403310 ER PT J AU Davis, JW Mills, EM Kane, MD Vanden Heuvel, JP AF Davis, JW Mills, EM Kane, MD Vanden Heuvel, JP TI The use of undifferentiated PC12 cells as a model system to study peroxisome proliferator-activated receptor (PPAR) signaling. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. NIH, Bethesda, MD 20892 USA. Warner Lambert Parke Davis, Ann Arbor, MI 48105 USA. Penn State Univ, Dept Vet Sci, University Pk, PA 16802 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 752 BP A129 EP A129 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006400750 ER PT J AU Diehl, N Yaswen, L Brennan, M Hochgeschwender, U AF Diehl, N Yaswen, L Brennan, M Hochgeschwender, U TI Obesity and differential survival rates of POMC null mutant mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1127 BP A194 EP A194 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401127 ER PT J AU Dwyer, JT Burrowes, JD Kusek, J Leung, J Makoff, R Maroni, BJ Paranandi, L Rocco, M AF Dwyer, JT Burrowes, JD Kusek, J Leung, J Makoff, R Maroni, BJ Paranandi, L Rocco, M CA Hemodialysis Study Grp TI Relationship between indicators of nutrition, clinical and demographic characteristics at baseline in the HEMO study SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1299 BP A222 EP A222 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401292 ER PT J AU Dye, JM Gao, J Murphy, PM Quinn, DG AF Dye, JM Gao, J Murphy, PM Quinn, DG TI Antiviral cell-mediated immune responses in CCR1-deficient mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Loyola Univ, Med Ctr, Dept Microbiol & Immunol, Maywood, IL 60153 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3356 BP A578 EP A578 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403352 ER PT J AU Finkelman, FD Noben-Trauth, N Donaldson, DD Madden, KB Morris, SC Collins, M Urban, JF AF Finkelman, FD Noben-Trauth, N Donaldson, DD Madden, KB Morris, SC Collins, M Urban, JF TI IL-13, IL-4 receptor alpha chain (IL-4R alpha), and Stat6, but not IL-4, are required to expel the GI nematode parasite Nippostrongylus brasiliensis. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Cincinnati, Coll Med, Cincinnati, OH 45267 USA. NIAID, NIH, Rockville, MD 20852 USA. Genet Inst, Cambridge, MA 02140 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. USDA, Beltsville, MD 20705 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3304 BP A569 EP A569 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403297 ER PT J AU Fleckenstein, AE Kokoshka, JM Vaughan, RA Metzger, RR Gibb, JW Hanson, GR AF Fleckenstein, AE Kokoshka, JM Vaughan, RA Metzger, RR Gibb, JW Hanson, GR TI Selective and reversible effects of methamphetamine on striatal dopamine transporters SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Utah, Dept Pharmacol Toxicol, Salt Lake City, UT 84112 USA. NIDA, Addict Res Ctr, IRP, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 928 BP A159 EP A159 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006400926 ER PT J AU Fleischmajer, R MacDonald, ED Perlish, JS Sapadin, AN Yomada, Y AF Fleischmajer, R MacDonald, ED Perlish, JS Sapadin, AN Yomada, Y TI Keratinocyte cell surface receptors are involved during early assembly of the basement membrane. SO FASEB JOURNAL LA English DT Meeting Abstract C1 CUNY Mt Sinai Sch Med, New York, NY 10029 USA. NIH, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 273 BP A47 EP A47 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006400275 ER PT J AU Forman, MR Zhang, J Gross, M Yao, SX Graubard, BI Qiao, YL Taylor, P Keith, S AF Forman, MR Zhang, J Gross, M Yao, SX Graubard, BI Qiao, YL Taylor, P Keith, S TI Blood and urinary antioxidant biomarkers of fruit and vegetable intake among Chinese tin miners. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Labor Protect Inst, Gejiu, Peoples R China. Informat Management Serv, Silver Spring, MD USA. RI Qiao, You-Lin/B-4139-2012 OI Qiao, You-Lin/0000-0001-6380-0871 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 2001 BP A344 EP A344 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401995 ER PT J AU Gao, JL Lee, EJ Westphal, H Elkins, EL Murphy, PM AF Gao, JL Lee, EJ Westphal, H Elkins, EL Murphy, PM TI Impaired host defense against Listeria monocytogenes in mice lacking the high affinity N-formylpeptide receptor SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3340 BP A575 EP A575 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403335 ER PT J AU Herman, E Zhang, J Hasinoff, B Tran, K Chadwick, D Clark, J Ferrans, V AF Herman, E Zhang, J Hasinoff, B Tran, K Chadwick, D Clark, J Ferrans, V TI Comparison of the chronic toxicity of piroxantrone (PXR), losoxantrone (LXR) and doxorubicin (DXR) in spontaneously hypertensive rats (SHR) SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Laurel, MD USA. Univ Manitoba, Winnipeg, MB, Canada. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 560 BP A96 EP A96 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006400561 ER PT J AU Hermann, P Armant, M Rubio, M Ishihara, H Ulrich, D Caspary, RG Armitage, R Maliszewski, C Delespesse, G Sarfati, M AF Hermann, P Armant, M Rubio, M Ishihara, H Ulrich, D Caspary, RG Armitage, R Maliszewski, C Delespesse, G Sarfati, M TI The vitronectin receptor complex (alpha v beta 3/CD47), mediates proinflammatory cytokine synthesis in human monocytes by interaction with soluble CD23. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Montreal, Ctr Hosp, Montreal, PQ, Canada. NIH, Parasit Dis Lab, Bethesda, MD USA. Immunex Res & Dev Corp, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3359 BP A579 EP A579 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403354 ER PT J AU Hilburger, ME Schlom, J Abrams, SI AF Hilburger, ME Schlom, J Abrams, SI TI Generation of murine wild-type p53 peptide-specific cytotoxic T lymphocyte lines that lyse tumor cells, but not normal cells: Implications for the development of p53-based cancer immunotherapies. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1683 BP A289 EP A289 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401680 ER PT J AU Hosohata, Y Sora, I Uhi, G Burkey, TH Hruby, V Roeske, WR Yamamura, HI AF Hosohata, Y Sora, I Uhi, G Burkey, TH Hruby, V Roeske, WR Yamamura, HI TI pCl-DPDPE and deltorphin II stimulate G protein activity through mu- and delta-opioid receptors as determined in mu knockout mouse brain membranes. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDA, Baltimore, MD 21224 USA. Univ Arizona, Hlth Sci Ctr, Tucson, AZ 85724 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 889 BP A152 EP A152 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006400884 ER PT J AU Hurwitz, AA Kwon, ED Foster, BA Burg, MB Greenberg, NM Allison, JP AF Hurwitz, AA Kwon, ED Foster, BA Burg, MB Greenberg, NM Allison, JP TI Rejection of a transplantable prostate tumor as a consequence of CTLA-4/B7 blockade is dependent on both T cells and NK cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Calif Berkeley, HHMI, Berkeley, CA 94720 USA. NIH, Bethesda, MD USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1678 BP A288 EP A288 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401672 ER PT J AU Johnson, SM Koizumi, H Trouth, CO Smith, JC AF Johnson, SM Koizumi, H Trouth, CO Smith, JC TI Chemosensory responses of the isolated respiratory network and pacemaker neurons in medullary slices in vitro. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, Neural Control Lab, NIH, Bethesda, MD 20892 USA. Howard Univ, Coll Med, Dept Physiol & Biophys, Washington, DC 20059 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 289 BP A50 EP A50 DI 10.1046/j.1365-2435.1998.00175.x PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006400291 ER PT J AU Koshiya, N Smith, JC AF Koshiya, N Smith, JC TI Real-time visualization of the neuronal kernel for respiratory rhythm generation with calcium-sensitive dyes in thin medullary slices in vitro. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, Neural Control Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 2870 BP A494 EP A494 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006402865 ER PT J AU Kuznetsova, N Chi, SL Leikin, S AF Kuznetsova, N Chi, SL Leikin, S TI Sugars and polyols inhibit collagen fibrillogenesis by disrupting hydrogen-bonded water bridges between the helices. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHD, LPSB, NIH, Bethesda, MD 20892 USA. Princeton Univ, Princeton, NJ 08544 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 282 BP A48 EP A48 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006400280 ER PT J AU Lifson, JD Rossio, JL Esser, MT Schneider, DK Bess, JW Grimes, MK Arthur, LO Hendersen, LE AF Lifson, JD Rossio, JL Esser, MT Schneider, DK Bess, JW Grimes, MK Arthur, LO Hendersen, LE TI Inactivation of HIV-1 infectivity with preservation of conformational and functional integrity of virion surface proteins. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, AIDS Vaccine Program, SAIC Frederick, FCRDC, Frederick, MD 21702 USA. RI Bess, Jr., Julian/B-5343-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1724 BP A296 EP A296 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401718 ER PT J AU Ludviksson, BR Strober, W Nishikomori, R Hasan, SK Ehrhardt, RO AF Ludviksson, BR Strober, W Nishikomori, R Hasan, SK Ehrhardt, RO TI In vivo administration of mAb against alpha 4 beta 7 and/or alpha IEL prevents the development of TNP-OVA-induced colitis in IL-2-/- mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Mucosal Immun Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3449 BP A594 EP A594 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403443 ER PT J AU MacLennan, MJ Tinney, JP Keller, BB AF MacLennan, MJ Tinney, JP Keller, BB TI In situ measurement of ventricular blood pressure in the mouse embryo. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Rochester, NIH, SCOR Pediat Cardiovasc Dis, Rochester, NY 14642 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1878 BP A323 EP A323 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401875 ER PT J AU Masereeuw, R Letcher, SG Miller, DS AF Masereeuw, R Letcher, SG Miller, DS TI Endothelin-1 (ET-1) acts through protein kinase C (PKC) to regulate Na-independent organic anion (OA) transport in renal proximal tubule. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Nijmegen, Dept Pharmacol, Nijmegen, Netherlands. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Mt Desert Isl Biol Lab, Salsbury Cove, ME 04672 USA. RI Masereeuw, Roos/N-3582-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 2461 BP A424 EP A424 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006402456 ER PT J AU Mason, L Willette-Brown, J Anderson, S Gosselin, P Shores, E Love, P Ortaldo, J McVicar, D AF Mason, L Willette-Brown, J Anderson, S Gosselin, P Shores, E Love, P Ortaldo, J McVicar, D TI Characterization of an associated 16 kDa tyrosine phosphoprotein required for Ly-49D signal transduction SO FASEB JOURNAL LA English DT Meeting Abstract C1 SAIC, Intramural Res Support Program, DBS, LEI, Frederick, MD USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NICHD, LMGD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3497 BP A602 EP A602 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403493 ER PT J AU Matsumoto, N Ribaudo, RK Abastado, JP Margulies, DH Yokoyama, WM AF Matsumoto, N Ribaudo, RK Abastado, JP Margulies, DH Yokoyama, WM TI The C-type lectin NK receptors Ly-49A recognizes carbohydrate-independent epitope on MHC class I molecules. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Washington Univ, HHMI, Sch Med, St Louis, MO 63110 USA. NCI, Lab Immune Cell Biol, Bethesda, MD 20892 USA. Inst Pasteur, Paris, France. NIAID, Immunol Lab, Bethesda, MD 20892 USA. RI Margulies, David/H-7089-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3493 BP A601 EP A601 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403488 ER PT J AU McCartney-Francis, N Frazier-Jessen, M Mizel, D Wahl, S AF McCartney-Francis, N Frazier-Jessen, M Mizel, D Wahl, S TI Aberrant expression of NF-kappa B and IFN regulatory factor-1 in TGF-beta 1 null mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1794 BP A308 EP A308 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401789 ER PT J AU McNeil, EM Campbell, K Keller, BB Hu, N AF McNeil, EM Campbell, K Keller, BB Hu, N TI Effect of increased circulating volume on diastolic filling in the stage 21 chick embryo. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Rochester, NIH, SCOR Pediat Cardiac Dis, Rochester, NY 14642 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1882 BP A323 EP A323 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401877 ER PT J AU Miller, DS Moons, MM Russel, FGM Masereeuw, R AF Miller, DS Moons, MM Russel, FGM Masereeuw, R TI Lucifer yellow (LY) secretion in renal proximal tubule: Evidence for organic anion (OA) transport system crossover. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Univ Nijmegen, Dept Pharmacol, Nijmegen, Netherlands. RI Russel, Frans/B-3184-2014; Masereeuw, Roos/N-3582-2014 OI Russel, Frans/0000-0002-7959-2314; NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 2472 BP A425 EP A425 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006402467 ER PT J AU Mills, E Katagiri, Y Guroff, G AF Mills, E Katagiri, Y Guroff, G TI Transcriptional regulation by peroxide in PC12 cells: Involvement of NGFI-B. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 767 BP A132 EP A132 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006400771 ER PT J AU Mittleman, BB Chiodetti, L AF Mittleman, BB Chiodetti, L TI Selective deficits in response to S-pyogenes in children with rheumatic fever Sydenham's chorea and PANDAS. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3312 BP A571 EP A571 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403307 ER PT J AU Mock, YD Higgins, SO Roth, GS AF Mock, YD Higgins, SO Roth, GS TI The effects of aging on protein kinase C regulation of DNA synthesis in rat hepatocytes SO FASEB JOURNAL LA English DT Meeting Abstract C1 Alabama State Univ, NIA, NIH, Montgomery, AL 36101 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1158 BP A199 EP A199 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401160 ER PT J AU Murphy, WJ Longo, DL Blazar, BR AF Murphy, WJ Longo, DL Blazar, BR TI Role of interferon-gamma in the pathobiology of graft-versus-host disease. SO FASEB JOURNAL LA English DT Meeting Abstract C1 SAIC Frederick, IRSP, Frederick, MD USA. NIA, Baltimore, MD 21224 USA. Univ Minnesota, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3393 BP A584 EP A584 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403388 ER PT J AU Naramura, M Gu, H AF Naramura, M Gu, H TI Mice with a fluorescent marker for interleukin 2 gene activation. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3572 BP A615 EP A615 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403569 ER PT J AU Natarajan, K Castellino, F Germain, RN Margulies, DH AF Natarajan, K Castellino, F Germain, RN Margulies, DH TI The zebrafish invariant chain assembles with murine I-A(d). SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, MBS, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIAID, LBS, Immunol Lab, NIH, Bethesda, MD 20892 USA. RI Margulies, David/H-7089-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3415 BP A588 EP A588 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403408 ER PT J AU Oriji, GK Tate, JE Coleman, BR Keiser, HR AF Oriji, GK Tate, JE Coleman, BR Keiser, HR TI Cyclosporine A-induced contractions and prostacyclin release are maintained by extracellular calcium in rat aortic rings: Role of protein kinase C. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Hypertens Endocrine Branch, NIH, Bethesda, MD 20892 USA. Howard Univ, Coll Med, Washington, DC 20059 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 531 BP A91 EP A91 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006400529 ER PT J AU Ortaldo, JR Winkler-Pickett, R Willette-Brown, J Anderson, S Palumbo, GJ Mason, L McVicar, D AF Ortaldo, JR Winkler-Pickett, R Willette-Brown, J Anderson, S Palumbo, GJ Mason, L McVicar, D TI Analysis of Ly-49D signal transduction, an activating NK receptor, in jurkat T cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, FCRDC, LEI, DBS, Bethesda, MD 20892 USA. NCI, FCRDC, SAIC, Bethesda, MD 20892 USA. Univ Oklahoma, Norman, OK 73019 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3510 BP A604 EP A604 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403503 ER PT J AU Rabin, RL Park, MK Liao, F Swofford, R Stephany, D Farber, JM AF Rabin, RL Park, MK Liao, F Swofford, R Stephany, D Farber, JM TI CXC and CC chemokines target different subsets of T cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3337 BP A575 EP A575 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403332 ER PT J AU Renfro, JL Miller, DS Dawson, MA Lechter, SG Fujukawa, S Toomey, B AF Renfro, JL Miller, DS Dawson, MA Lechter, SG Fujukawa, S Toomey, B TI Glycine stimulates teleost renal tubule organic anion (OA) secretion. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Mt Desert Isl Biol Lab, Salsbury Cove, ME 04672 USA. Univ Connecticut, Storrs, CT 06269 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 2471 BP A425 EP A425 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006402464 ER PT J AU Rudensky, AY Dongre, AR Kovats, S deRoos, P Nakagawa, T McCormack, AL Eng, J Yates, JR Caldwell, H AF Rudensky, AY Dongre, AR Kovats, S deRoos, P Nakagawa, T McCormack, AL Eng, J Yates, JR Caldwell, H TI In vivo MHC class II presentation of cytosolic proteins revealed by rapid automated tandem mass spectrometry and functional analyses. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Washington, Sch Med, Howard Hughes Med Inst, Seattle, WA 98115 USA. Univ Washington, Sch Med, Dept Immunol, Seattle, WA 98115 USA. Univ Washington, Sch Med, Dept Mol Biotechnol, Seattle, WA 98115 USA. NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Hamilton, MT 59840 USA. RI Eng, Jimmy/I-4202-2012; Eng, Jimmy/C-6556-2017 OI Eng, Jimmy/0000-0001-6352-6737; Eng, Jimmy/0000-0001-6352-6737 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3428 BP A590 EP A590 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403423 ER PT J AU Rumsey, SC Zarnowski, MJ Simson, IA Levine, M AF Rumsey, SC Zarnowski, MJ Simson, IA Levine, M TI DHA transport by GLUT4 in xenopus oocytes and isolated rat adipocytes. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDKD, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 2667 BP A459 EP A459 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006402663 ER PT J AU Ryan, R Weber, HC Mantey, S Pradhan, T Hou, W Jensen, R AF Ryan, R Weber, HC Mantey, S Pradhan, T Hou, W Jensen, R TI Pharmacology and intracellular signaling of the human orphan receptor BRS-3 in lung cancer cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 896 BP A154 EP A154 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006400900 ER PT J AU Sai, Y Dai, R Yang, T Rushmore, T Baillie, TA Gonzalez, FJ Gelboin, HV Shou, M AF Sai, Y Dai, R Yang, T Rushmore, T Baillie, TA Gonzalez, FJ Gelboin, HV Shou, M TI Inhibition kinetics of monoclonal antibodies against cytochrome P450-mediated drug metabolism. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Merck Res Labs, Dept Drug Metab, W Point, PA 19486 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 848 BP A146 EP A146 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006400853 ER PT J AU Schnermann, JB Traynor, T Yang, T Huang, YG Krege, JH Smithies, O Briggs, JP AF Schnermann, JB Traynor, T Yang, T Huang, YG Krege, JH Smithies, O Briggs, JP TI Tubuloglomerular feedback in angiotensin converting enzyme (ACE)-deficient mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. NIH, DRCHD, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 632 BP A108 EP A108 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006400631 ER PT J AU Shankavaram, UT Wahl, LM AF Shankavaram, UT Wahl, LM TI Role of MAP kinases in monocyte matrix metalloproteinase production SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDR, Immunopathol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1747 BP A300 EP A300 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401744 ER PT J AU Shou, M Lu, T Mei, Q Rushmore, T Baillie, TA Gonzalez, FJ Gelboin, HV AF Shou, M Lu, T Mei, Q Rushmore, T Baillie, TA Gonzalez, FJ Gelboin, HV TI Using monoclonal antibodies to assess the contribution of individual cytochrome P450s to drug metabolism in human liver SO FASEB JOURNAL LA English DT Meeting Abstract C1 Merck Res Labs, Dept Drug Metab, W Point, PA 19486 USA. NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 847 BP A145 EP A145 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006400842 ER PT J AU Snodgress, S Popescu, NC Bonner, TI Printz, MP Klett, CPR AF Snodgress, S Popescu, NC Bonner, TI Printz, MP Klett, CPR TI Functional analysis and chromosomal location of the muscarinic m1 receptor promoter SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA. HIMH, Bethesda, MD USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 2088 BP A359 EP A359 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006402084 ER PT J AU Srirangam, A Wolisi, GO Overwijk, W Restifo, NP Dass, VS Kwon, BS AF Srirangam, A Wolisi, GO Overwijk, W Restifo, NP Dass, VS Kwon, BS TI Vaccination of Pmel17, a self melanoma-antigen rejects the melanoma in Pmel17 deficient mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Indiana Univ, Sch Med, Indianapolis, IN 46202 USA. NCI, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1628 BP A279 EP A279 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401623 ER PT J AU Stolzenberg-Solomon, RZ Appel, LJ Miller, ER Maquire, MG Sehlub, J AF Stolzenberg-Solomon, RZ Appel, LJ Miller, ER Maquire, MG Sehlub, J TI The impact of dietary intake of protein and coffee consumption on serum homocysteine concentration in an older aged population. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Hyg, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. Univ Penn, Philadelphia, PA 19104 USA. Tufts Univ, USDA, Human Nutr Res Ctr, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1333 BP A228 EP A228 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401326 ER PT J AU Suzuki, Y Liesenfeld, O Kang, H Nguyen, TA Parkhe, CV Sher, A Remington, JS AF Suzuki, Y Liesenfeld, O Kang, H Nguyen, TA Parkhe, CV Sher, A Remington, JS TI A critical role for IFN-gamma, TNF-alpha and nitric oxide (NO) in genetic susceptibility of mice to peroral infection with Toxoplasma gondii. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Palo Alto Med Fdn, Res Inst, Palo Alto, CA 94301 USA. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3322 BP A572 EP A572 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403315 ER PT J AU Suzuki, YJ Shi, SS Day, RM Chedid, M Blumberg, JB AF Suzuki, YJ Shi, SS Day, RM Chedid, M Blumberg, JB TI Homocysteine activates p44/42 MAP kinase through p21(ras)-dependent pathways. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. NCI, NIH, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1097 BP A188 EP A188 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401098 ER PT J AU Talan, M Roukoyatkina, N Chefer, S Ajmani, R Rifkind, J AF Talan, M Roukoyatkina, N Chefer, S Ajmani, R Rifkind, J TI Cold-induced increase of arterial blood pressure in rats: Model of hypertension. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 542 BP A93 EP A93 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006400543 ER PT J AU Thornton, AM Suri-Payer, E Sheyach, EM AF Thornton, AM Suri-Payer, E Sheyach, EM TI CD4+CD25+ professional suppressor cells inhibit T cell activation by blocking IL-2 synthesis SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3594 BP A618 EP A618 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403589 ER PT J AU Tinney, JP Keller, BB AF Tinney, JP Keller, BB TI Ventricular function after chronic conotruncal banding in the chick embryo. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Rochester, NIH, SCOR Pediat Cardiovasc Dis, Rochester, NY 14642 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1883 BP A324 EP A324 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401878 ER PT J AU Traynor, T Yang, T Huang, YG Arend, L Oliverio, MI Coffman, T Briggs, JP Schnermann, JB AF Traynor, T Yang, T Huang, YG Arend, L Oliverio, MI Coffman, T Briggs, JP Schnermann, JB TI Inhibition of adenosine(1) receptor-mediated glomerular vasoconstriction in AT(1A)-receptor deficient mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, DKUHD, Bethesda, MD USA. Univ Michigan, Ann Arbor, MI 48109 USA. Duke Univ, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1926 BP A331 EP A331 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401919 ER PT J AU Tsang, KY Correale, P Zhu, M Terasawa, H Arlen, P Zaremba, S Schlom, J AF Tsang, KY Correale, P Zhu, M Terasawa, H Arlen, P Zaremba, S Schlom, J TI Generation of CEA peptide-specific cytotoxic T cells in vivo from HLA-A2.1K(b) transgenic mice using peptide-pulsed bone marrow (BM)-derived dendritic cells (DC). SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1613 BP A277 EP A277 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401607 ER PT J AU Vieira, NE Goans, RE Weiss, GH Marini, JC Hopkins, E Yergey, AL AF Vieira, NE Goans, RE Weiss, GH Marini, JC Hopkins, E Yergey, AL TI Calcium kinetics in children with Osteogenesis imperfecta type III and IV: Pre- and post-growth hormone therapy SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD 20892 USA. NIH, DCRT, Bethesda, MD 20892 USA. Oak Ridge Associated Univ, REACTS, Oak Ridge, TN 37716 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3174 BP A547 EP A547 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403171 ER PT J AU Visser, M Kiel, DP Haffner, SM Roubenoff, R Abad, L Wilson, PWF Harris, TB AF Visser, M Kiel, DP Haffner, SM Roubenoff, R Abad, L Wilson, PWF Harris, TB TI Past weight gain is associated with lower plasma leptin concentrations: The Framingham Heart Study. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 2048 BP A352 EP A352 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006402044 ER PT J AU Wang, S Wang, W Wesley, R Danner, RL AF Wang, S Wang, W Wesley, R Danner, RL TI Nitric oxide activates the tumor necrosis factor-alpha promoter through an Sp1-binding site SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1753 BP A301 EP A301 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401750 ER PT J AU Wei, H Chen, RW Leed, P Leng, Y Chuang, DM AF Wei, H Chen, RW Leed, P Leng, Y Chuang, DM TI Dantrolene and bcl-2 suppress neuronal cell death induced by 3-hydroxykynurenine. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 2701 BP A465 EP A465 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006402695 ER PT J AU Xu, T Hauser, W Nishimura, Y Saavedra, JM AF Xu, T Hauser, W Nishimura, Y Saavedra, JM TI Prolonged treatment with the AT1 antagonist CV-11974 shifts the cerebral blood flow autoregulation towards lower pressures in hypertensive and normotensive rats SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH, Pharmacol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 649 BP A111 EP A111 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006400646 ER PT J AU Yang, LP Riley, JL Carroll, RG June, CH Hoxie, J Patterson, BK Ohshima, Y Hodes, RJ Delespesse, G AF Yang, LP Riley, JL Carroll, RG June, CH Hoxie, J Patterson, BK Ohshima, Y Hodes, RJ Delespesse, G TI Productive infection of neonatal CD8+ T lymphocytes by HIV-1 SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Montreal, Montreal, PQ H2L 4M1, Canada. Henry M Jackson Fdn Advancement Mil Med, Bethesda, MD 20889 USA. NIH, Bethesda, MD 20892 USA. Northwestern Univ, Sch Med, Chicago, IL 60611 USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1784 BP A306 EP A306 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401778 ER PT J AU Yap, G Scharton-Kersten, T Charest, H Sher, A AF Yap, G Scharton-Kersten, T Charest, H Sher, A TI Distinct roles of inducible nitric oxide synthase and tumor necrosis factor receptors in immune control of toxoplasmosis in the brain. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, LPD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3302 BP A569 EP A569 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403296 ER PT J AU Yoshimura, T Ueda, A Ishigatsubo, Y Okubo, T AF Yoshimura, T Ueda, A Ishigatsubo, Y Okubo, T TI Transcriptional regulation of the human monocyte chemoattractant protein-1 (MCP-1) gene: Cooperation of two NF-kappa B sites and NF-kappa B/Rel subunit specificity. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Yokohama City Univ, Yokohama, Kanagawa 232, Japan. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1593 BP A274 EP A274 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401588 ER PT J AU Yuan, DS AF Yuan, DS TI Possible involvement of a lipid phosphatase in zinc homeostasis: Initial results of a systematic analysis of zinc-regulated genes in yeast. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 2016 BP A347 EP A347 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006402013 ER PT J AU Zhang, L Gan, XH Roher, A Sherry, B Taub, D Vinters, HS Hama, S Way, D Witte, M Weinand, M Graves, MC Fiala, M AF Zhang, L Gan, XH Roher, A Sherry, B Taub, D Vinters, HS Hama, S Way, D Witte, M Weinand, M Graves, MC Fiala, M TI Amyloid-beta induces chemokine secretion and monocyte migration across the blood-brain barrier: Role in the inflammatory reaction in Alzheimer's disease brain SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Pathol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. Sun Hlth Res Inst, Sun City, AZ 85372 USA. Picower Inst Med Res, Manhasset, NY 10030 USA. NIA, Baltimore, MD 21224 USA. Univ Arizona, Dept Surg, Tucson, AZ USA. Univ Arizona, Dept Neurosurg, Tucson, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1743 BP A299 EP A299 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401739 ER PT J AU Zhang, YH McCluskey, K Fujii, K Wahl, LM AF Zhang, YH McCluskey, K Fujii, K Wahl, LM TI Differential regulation of monocyte matrix metalloproteinases and TIMP-1 by cytokines. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDR, Immunopathol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1073 BP A184 EP A184 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401074 ER PT J AU Gottesman, S AF Gottesman, S TI Protecting the neighborhood: Extreme measures SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID PROTEIN-SYNTHESIS; TOXIN C1 NCI, Bethesda, MD 20892 USA. RP Gottesman, S (reprint author), NCI, Bldg 37,Room 2E18, Bethesda, MD 20892 USA. EM susang@helix.nih.gov NR 16 TC 8 Z9 8 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 17 PY 1998 VL 95 IS 6 BP 2731 EP 2732 DI 10.1073/pnas.95.6.2731 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZC589 UT WOS:000072596200006 PM 9501157 ER PT J AU Berlett, BS Levine, RL Stadtman, ER AF Berlett, BS Levine, RL Stadtman, ER TI Carbon dioxide stimulates peroxynitrite-mediated nitration of tyrosine residues and inhibits oxidation of methionine residues of glutamine synthetase: Both modifications mimic effects of adenylylation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MECHANISM AB The activity of glutamine synthetase (EC 6.3.1.2) from Escherichia coli is regulated by the cyclic adenylylation and deadenylylation of Tyr-397 in each of the enzyme's 12 identical subunits. The nitration of Tyr-397 or of the nearby Tyr-326 by peroxynitrite can convert the unadenylylated enzyme to a form exhibiting regulatory characteristics similar to the form obtained by adenylylation. The adenylylated conformation can also be elicited by the oxidation of surface-exposed methionine residues to methionine sulfoxide. However, the nitration of tyrosine residues and the oxidation of methionine residues are oppositely directed by the presence and absence of CO2. At physiological concentrations of CO2, pH 7.4, nitration occurs but oxidation of methionine residues is inhibited. Conversely, in the absence of CO2 methionine oxidation is stimulated and nitration of tyrosine is prevented, It was further established that adenylylation of Tyr-397 precludes its nitration by peroxynitrite. Furthermore, nitration of Tyr-326 together with either nitration or adenylylation of Tyr-397 leads to inactivation of the enzyme. These results demonstrate that CO2 can alter the course of peroxynitrite-dependent reactions and serve notice that (i) the reactions have physiological significance only if they are shown to occur at physiological concentrations of CO2 and physiological pH; and (ii) the peroxynitrite-dependent nitration of tyrosine residues or the oxidation of methionine residues of metabolically regulated proteins can seriously compromise their biological function. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Stadtman, ER (reprint author), NHLBI, Biochem Lab, NIH, 3 Ctr Dr,MSC 0342, Bethesda, MD 20892 USA. EM erstadtman@nih.gov RI Levine, Rodney/D-9885-2011 NR 18 TC 116 Z9 118 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 17 PY 1998 VL 95 IS 6 BP 2784 EP 2789 DI 10.1073/pnas.95.6.2784 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZC589 UT WOS:000072596200016 PM 9501167 ER PT J AU Sices, HJ Kristie, TM AF Sices, HJ Kristie, TM TI A genetic screen for the isolation and characterization of site-specific proteases SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; TRANSCRIPTION FACTOR; RETROVIRAL PROTEASES; IN-VIVO; ACTIVATION; PROTEOLYSIS; EXPRESSION; PROTEINASE; RESISTANCE; INHIBITORS AB Site-specific proteolysis is an important regulatory mechanism in basic cellular and viral processes. Using the protease of the HIV as a model, a genetic system has been developed for the isolation and characterization of site-specific proteases. The system utilizes the well defined bacteriophage lambda regulatory circuit where the viral repressor, cI, is specifically cleaved to initiate the lysogenic-to-lytic switch. The model system is rapid, highly specific, and demonstrates the ability to isolate and characterize enzymes of limited expression or activity. In addition, the system has a significant potential for the selection of clinically relevant mutant enzymes and in the development of anti-protease therapeutics. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Kristie, TM (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 4,Room 133,9000 Rockville Pike, Bethesda, MD 20892 USA. EM Thomas_Kristie@nih.gov NR 47 TC 28 Z9 28 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 17 PY 1998 VL 95 IS 6 BP 2828 EP 2833 DI 10.1073/pnas.95.6.2828 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZC589 UT WOS:000072596200024 PM 9501175 ER PT J AU Zhou, YN Jin, DJ AF Zhou, YN Jin, DJ TI The rpoB mutants destabilizing initiation complexes at stringently controlled promoters behave like "stringent" RNA polymerases in Escherichia coli SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRANSCRIPTIONAL INITIATION; GUANOSINE TETRAPHOSPHATE; PYRBI OPERON; DNA; INVITRO; PPGPP; EXPRESSION; ACTIVATION; PHENOTYPES; BINDING AB In Escherichia coli, stringently controlled genes are highly transcribed during rapid growth, but "turned off" under nutrient limiting conditions, a process called the stringent response. To understand how transcriptional initiation at these promoters is coordinately regulated, we analyzed the interactions between RNA polymerase (RNAP) (both wild type and mutants) and four stringently controlled promoters, Our results show that the interactions between RNAP and stringently controlled promoters are intrinsically unstable and can alternate between relatively stable and metastable states. The mutant RNAPs appear to specifically further weaken interactions with these promoters in vitro and behave like "stringent" RNAPs in the absence of the stringent response in vivo, constituting a novel class of mutant RNAPs, Consistently, these mutant RNAPs also activate the expression of other genes that normally require the response. We propose that the stability of initiation complexes is coupled to the transcription of stringently controlled promoters, and this unique feature coordinates the expression of genes positively and negatively regulated by the stringent response. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Jin, DJ (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37,Room 2E14,9000 Rockville Pike, Bethesda, MD 20892 USA. EM djjin@helix.nih.gov NR 38 TC 142 Z9 144 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 17 PY 1998 VL 95 IS 6 BP 2908 EP 2913 DI 10.1073/pnas.95.6.2908 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZC589 UT WOS:000072596200038 PM 9501189 ER PT J AU Cheng, Y Poulos, NE Lung, ML Hampton, G Ou, BX Lerman, MI Stanbridge, EJ AF Cheng, Y Poulos, NE Lung, ML Hampton, G Ou, BX Lerman, MI Stanbridge, EJ TI Functional evidence for a nasopharyngeal carcinoma tumor suppressor gene that maps at chromosome 3p21.3 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LUNG-CANCER; TUMORIGENIC EXPRESSION; WILMS-TUMOR; LOCUS; IDENTIFICATION; HETEROZYGOSITY; REGION; CHINESE; CELLS; CLONE AB Nasopharyngeal carcinoma is a malignancy that is prevalent among populations from Southeast Asia. Epidemiological studies indicate that genetic predisposition, Epstein-Barr virus, and environmental conditions may play a role in determining incidence. Molecular studies have implicated a tumor suppressor gene(s) on the short arm of chromosome 3. In this study we provide functional evidence, via monochromosome transfer, for a tumor suppressor gene(s) activity in chromosome 3p21.3. C1 Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92697 USA. Hong Kong Univ Sci & Technol, Dept Biol, Hong Kong, Hong Kong. Genos Biosci Inc, La Jolla, CA 92037 USA. Sun Yatsen Univ Med Sci, Inst Canc, Guangzhou, Peoples R China. NCI, Frederick, MD 21702 USA. RP Stanbridge, EJ (reprint author), Univ Calif Irvine, Dept Microbiol & Mol Genet, 240 Med Sci 1,Bldg B, Irvine, CA 92697 USA. EM ejstanbr@uci.edu RI Cheng, Yue/E-9853-2010 OI Cheng, Yue/0000-0002-2472-1879 FU NCI NIH HHS [CA19401] NR 46 TC 91 Z9 101 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 17 PY 1998 VL 95 IS 6 BP 3042 EP 3047 DI 10.1073/pnas.95.6.3042 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZC589 UT WOS:000072596200061 PM 9501212 ER PT J AU Conant, K Garzino-Demo, A Nath, A McArthur, JC Halliday, W Power, C Gallo, RC Major, EO AF Conant, K Garzino-Demo, A Nath, A McArthur, JC Halliday, W Power, C Gallo, RC Major, EO TI Induction of monocyte chemoattractant protein-1 in HIV-1 Tat-stimulated astrocytes and elevation in AIDS dementia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chemotaxis; central nervous system ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; NF-KAPPA-B; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MESSENGER-RNA; CHEMOTACTIC CYTOKINES; ACTIVATING-FACTOR; TYPE-1 INFECTION; EXPRESSION; BRAIN AB Activated monocytes release a number of substances, including inflammatory cytokines and eicosanoids, that are highly toxic to cells of the central nervous system. Because monocytic infiltration of the central nervous system closely correlates with HIV-1-associated dementia, it has been suggested that monocyte-derived toxins mediate nervous system damage. In the present study, we show that the HIV-1 transactivator protein Tat significantly increases astrocytic expression and release of monocyte chemoattractant protein-1 (MCP-1). Astrocytic release of beta-chemokines, which are relatively less selective for monocytes, including RANTES, macrophage inflammatory protein-1 alpha, and macrophage inflammatory protein-1 beta, was not observed. We also show that MCP-1 is expressed in the brains of patients with HIV-1-associated dementia and that, of the beta-chemokines tested, only MCP-1 could be detected in the cerebrospinal fluid of patients with this condition. Together, these data provide a potential link between the presence of HIV-1 in the brain and the monocytic infiltration that may substantially contribute to dementia. C1 NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. Univ Manitoba, Dept Internal Med, Neurol Sect, Winnipeg, MB R3E 0W3, Canada. Univ Manitoba, Dept Med Microbiol, Winnipeg, MB R3E 0W3, Canada. Univ Manitoba, Dept Pathol, Winnipeg, MB R3E 0W3, Canada. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD 21287 USA. RP Conant, K (reprint author), NINDS, Lab Mol Med & Neurosci, NIH, Bldg 36,Room 5W21, Bethesda, MD 20892 USA. EM conant@codon.nih.gov RI Power, Christopher/C-7181-2013; OI Power, Christopher/0000-0002-5131-9711 NR 44 TC 420 Z9 431 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 17 PY 1998 VL 95 IS 6 BP 3117 EP 3121 DI 10.1073/pnas.95.6.3117 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZC589 UT WOS:000072596200074 PM 9501225 ER PT J AU Hampton, LL Ladenheim, EE Akeson, M Way, JM Weber, HC Sutliff, VE Jensen, RT Wine, LJ Arnheiter, H Battey, JF AF Hampton, LL Ladenheim, EE Akeson, M Way, JM Weber, HC Sutliff, VE Jensen, RT Wine, LJ Arnheiter, H Battey, JF TI Loss of bombesin-induced feeding suppression in gastrin-releasing peptide receptor-deficient mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SWISS 3T3 CELLS; NEUROMEDIN-B; FOOD-INTAKE; MOLECULAR-CLONING; GENE-EXPRESSION; SUBTYPES; STIMULATION; ANTAGONIST; BEHAVIOR; GROWTH AB The gastrin-releasing peptide receptor (GRP-R) is one of three members of the mammalian bombesin subfamily of seven-transmembrane G protein coupled receptors that mediate diverse biological responses including secretion, neuromodulation, chemotaxis, and growth. The X chromosome-linked GRP-R gene is expressed widely during embryonic development and predominantly in gastrointestinal, neuronal, and neuroendocrine systems in the adult. Surprisingly, gene-targeted mice lacking a functional GRP-R gene develop and reproduce normally and show no gross phenotypic abnormalities. However, peripheral administration of bombesin at dosages up to 32 nmol/kg to such mice had no effect on the suppression of glucose intake, whereas normal mice showed a dose-dependent suppression of glucose intake. These data suggest that selective agonists for the GRP-R may be useful in inducing satiety. C1 NIDODS, Mol Biol Lab, NIH, Rockville, MD 20850 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA. Glaxo Wellcome Pharmaceut Co, Res Triangle Pk, NC 27701 USA. Boston Univ, Sch Med, Gastroenterol Sect, Med Ctr, Boston, MA 02118 USA. NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. NINDS, Lab Dev Neurogenet, Bethesda, MD 20892 USA. RP Battey, JF (reprint author), NIDODS, Mol Biol Lab, NIH, Rockville, MD 20850 USA. NR 37 TC 69 Z9 69 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 17 PY 1998 VL 95 IS 6 BP 3188 EP 3192 DI 10.1073/pnas.95.6.3188 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZC589 UT WOS:000072596200087 PM 9501238 ER PT J AU Celli, G LaRochelle, WJ Mackem, S Sharp, R Merlino, G AF Celli, G LaRochelle, WJ Mackem, S Sharp, R Merlino, G TI Soluble dominant-negative receptor uncovers essential roles for fibroblast growth factors in multi-organ induction and patterning SO EMBO JOURNAL LA English DT Article DE dominant-negative; FGF; limb; organogenesis; transgenic mice ID MAMMALIAN LUNG DEVELOPMENT; APICAL ECTODERMAL RIDGE; CHICK LIMB DEVELOPMENT; TRANSGENIC MICE; CELLULAR-DIFFERENTIATION; BRANCHING MORPHOGENESIS; MONOCLONAL-ANTIBODY; TARGETED EXPRESSION; KERATIN EXPRESSION; MOUSE DEVELOPMENT AB Despite a wealth of experimental data implicating fibroblast growth factor (FGF) signaling in various developmental processes, genetic inactivation of individual genes encoding specific FGFs or their receptors (FGFRs) has generally failed to demonstrate their role in vertebrate organogenesis due to early embryonic lethality or functional redundancy. Here we show that broad mid-gestational expression of a novel secreted kinase-deficient receptor, specific for a defined subset of the FGF superfamily, caused agenesis or severe dysgenesis of kidney, lung, specific cutaneous structures, exocrine and endocrine glands, and craniofacial and limb abnormalities reminiscent of human skeletal disorders associated with FGFR mutations. Analysis of diagnostic molecular markers revealed that this soluble dominant-negative mutant disrupted early inductive signaling in affected tissues, indicating that FGF signaling is required for growth and patterning in a broad array of organs and in limbs. In contrast, transgenic mice expressing a membrane-tethered kinase-deficient FGFR were viable. Our results demonstrate that secreted FGFR mutants are uniquely effective as dominant-negative agents in vivo, and suggest that related soluble receptor isoforms expressed in wild-type mouse embryos may help regulate FGF activity during normal development. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Merlino, G (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. NR 86 TC 283 Z9 287 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 16 PY 1998 VL 17 IS 6 BP 1642 EP 1655 DI 10.1093/emboj/17.6.1642 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZD515 UT WOS:000072693700010 PM 9501086 ER PT J AU Safrany, ST Shears, SB AF Safrany, ST Shears, SB TI Turnover of bis-diphosphoinositol tetrakisphosphate in a smooth muscle cell line is regulated by beta(2)-adrenergic receptors through a cAMP-mediated, A-kinase-independent mechanism SO EMBO JOURNAL LA English DT Article DE beta-adrenergic; cAMP; fluoride; inositol phosphates; receptor ID DEPENDENT PROTEIN-KINASE; INOSITOL HEXAKISPHOSPHATE; ADENYLATE-CYCLASE; PHOSPHORYLATION; BINDING; INHIBITION; ACTIVATION; METABOLISM; ALUMINUM; FLUORIDE AB Bis-diphosphoinositol tetrakisphosphate ([PP](2)-InsP(4) or 'InsP(s)') is a 'high-energy' inositol phosphate; we report that its metabolism is receptor-regulated in DDT1 MF-2 smooth muscle cells. This conclusion arose by pursuing the mechanism by which F- decreased cellular levels of [PP](2)-InsP(4) up to 70%. A similar effect was induced by elevating cyclic nucleotide levels, either with IBMX or by application of either Bt(2)cAMP (EC50 = 14.7 mu M), Bt(2)cGMP (EC50 = 7.9 mu M) or isoproterenol (EC50 = 0.4 nM). Isoproterenol (1 mu M) decreased [PP](2)-InsP(4) levels 25% by 5 min, and 71% by 60 min. This novel, agonist-mediated regulation of [PP](2)-InsP(4) turnover was very specific; isoproterenol did not decrease the cellular levels of either inositol pentakisphosphate, inositol hexakisphosphate or other diphosphorylated inositol polyphosphates. Bradykinin, which activated phospholipase C, did not affect [PP](2)InsP(4) levels. Regulation of [PP]2-InsP(4) turnover by both isoproterenol and cell-permeant cyclic nucleotides was unaffected by inhibitors of protein kinases A and G. The effectiveness of the kinase inhibitors was confirmed by their ability to block phosphorylation of the cAMP response element-binding protein. Our results indicate a new signaling action of cAMP, and furnish an important focus for future research into the roles of diphosphorylated inositol phosphates in signal transduction. C1 NIEHS, Inositide Signaling Grp, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Safrany, ST (reprint author), NIEHS, Inositide Signaling Grp, Lab Signal Transduct, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM Safrany@niehs.nih.gov NR 30 TC 45 Z9 46 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 16 PY 1998 VL 17 IS 6 BP 1710 EP 1716 DI 10.1093/emboj/17.6.1710 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZD515 UT WOS:000072693700016 PM 9501092 ER PT J AU Singleton, TL Wilcox, E AF Singleton, TL Wilcox, E TI The largest subunit of mouse RNA polymerase II (RPB1) functionally substituted for its yeast counterpart in vivo SO GENE LA English DT Article DE transcription; homologous recombination; Saccharomyces cerevisiae; haploid; promoter; gene replacement ID C-TERMINAL DOMAIN; SACCHAROMYCES-CEREVISIAE; HEPTAPEPTIDE REPEAT; TRANSCRIPTION; CHROMOSOMES; DISRUPTION; MUTATIONS; INVITRO; DNA AB The full-length mouse RNA polymerase II (pol II) largest subunit (RPB1) gene was used to replace 5070 bp of the yeast Saccharomyces cerevisiae RPB1 gene via homologous recombination and gene replacement in vivo. Transcription of the mouse RPB1 gene using the yeast promoter in the haploid state was confirmed by Northern analysis. This strain of yeast is viable, indicating that mouse RPB1 is able to interact functionally with the other yeast RNA pol II subunits in vivo. (C) 1998 Elsevier Science B.V. C1 Natl Inst Deafness & Commun Disorders, Mol Genet Lab, NIH, Rockville, MD 20850 USA. RP NICHHD, Lab Eukaryot Gene Regulat, NIH, Bldg 6B,Room 2B-220, Bethesda, MD 20892 USA. NR 29 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 EI 1879-0038 J9 GENE JI Gene PD MAR 16 PY 1998 VL 209 IS 1-2 BP 131 EP 138 DI 10.1016/S0378-1119(98)00025-0 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA ZF866 UT WOS:000072941100017 PM 9524248 ER PT J AU Dey, BR Furlanetto, RW Nissley, SP AF Dey, BR Furlanetto, RW Nissley, SP TI Cloning of human p55 gamma, a regulatory subunit of phosphatidylinositol 3-kinase, by a yeast two-hybrid library screen with the insulin-like growth factor-I receptor SO GENE LA English DT Article DE insulin receptor; p55(PIK); IRS-1; p85 alpha; p85 beta ID PHOSPHOINOSITIDE 3-KINASE; SUBSTRATE-1; ACTIVATION; ASSOCIATION; ADIPOCYTES; WORTMANNIN; BINDING; KINASE; SYSTEM; IRS-1 AB We have used the yeast two-hybrid system to identify proteins that interact with the intracellular domain of the insulin-like growth factor-I receptor (IGFIR). In a search of a human fetal brain library we identified a cDNA encoding a protein that is the human homologue of mouse p55(PIK), a regulatory subunit of phosphatidylinositol 3-kinase (hp55 gamma). The hp55 gamma protein interacts strongly with the activated IGFIR but not with the kinase-negative mutant receptor. hp55 gamma also interacts with the insulin receptor (IR) in the yeast two-hybrid system. The putative hp55 gamma protein is composed of a unique amino terminal region followed by a proline-rich motif and two Src homology 2 (SH2) domains, which are highly homologous to those in mouse p55(PIK), rat p55 gamma, human p85 alpha and bovine p85 beta; it contains no SH3 domain. hp55 gamma mRNAs are expressed in most human fetal and adult tissues with particularly high abundance in adult testis. Splice variant(s) of hp55 gamma, one of which has a deletion of 36 amino acids at the amino terminus and another which has an insertion of 59 amino acids at position 256 between the SH2 domains, were also identified. A GST-hp55 gamma fusion protein interacts in vitro with both the activated IGFIR and IR derived from mammalian cells. Our findings suggest that hp55 gamma interacts with the IGFIR and IR and may be involved in PI 3-kinase activation by these receptors. (C) 1998 Elsevier Science B.V. C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. Univ Rochester, Sch Med & Dent, Dept Pediat, Strong Childrens Res Ctr, Rochester, NY 14642 USA. RP Nissley, SP (reprint author), NCI, Metab Branch, NIH, Bldg 10,Room 4N115,10 Ctr Dr, Bethesda, MD 20892 USA. NR 29 TC 28 Z9 30 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAR 16 PY 1998 VL 209 IS 1-2 BP 175 EP 183 DI 10.1016/S0378-1119(98)00045-6 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA ZF866 UT WOS:000072941100022 PM 9524259 ER PT J AU Ambrosone, CB Freudenheim, JL Sinha, R Graham, S Marshall, JR Vena, JE Laughlin, R Nemoto, T Shields, PG AF Ambrosone, CB Freudenheim, JL Sinha, R Graham, S Marshall, JR Vena, JE Laughlin, R Nemoto, T Shields, PG TI Breast cancer risk, meat consumption and N-acetyltransferase (NAT2) genetic polymorphisms SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID HETEROCYCLIC AMINES; FAT AB Although inconsistencies exist, some studies have shown that meat consumption is associated with breast cancer risk. Several heterocyclic amines (HAs), formed in the cooking of meats, are mammary carcinogens in laboratory models. HAs are activated by polymorphic N-acetyltransferase (NAT2) and rapid NAT2 activity may increase risk associated with HAs. We investigated whether ingestion of meat, chicken and fish, as well as particular concentrated sources of HAs, was associated with breast cancer risk, and if NAT2 genotype modified risk. Caucasian women with incident breast cancer (n = 740) and community controls (n = 810) were interviewed and administered a food frequency questionnaire. A subset of these women (n = 793) provided a blood sample. Polymerase chain reaction and restriction fragment length polymorphism analyses were used to determine NAT2 genotype. Consumption of red meats, as well as an index of concentrated sources of HAs, was not associated with increased breast cancer risk, nor did risk vary by NAT2 genotype. In post-menopausal women, higher fish consumption was inversely associated with risk (odds ratio = 0.7; 95% confidence interval, 0.4-1.0); among pre-menopausal women, there was the suggestion of inverse associations between risk and pork and chicken intake. Our results suggest that consumption of meats and other concentrated sources of HAs is not associated with increased breast cancer risk. However, due to the strong biologic plausibility for a role of some HAs in mammary carcinogenesis, and the likely measurement error in evaluation of sources of HAs in this study, further studies of these possible relationships are warranted. (C) 1998 Wiley-Liss, Inc. C1 Natl Ctr Toxicol Res, Div Mol Endocrinol, Jefferson, AR 72079 USA. SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Rockville, MD USA. Univ Arizona, Div Canc Prevent & Control, Tucson, AZ USA. NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Ambrosone, CB (reprint author), Natl Ctr Toxicol Res, Div Mol Endocrinol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM cambrosone@nctr.fda.gov; peter_g_shields@nih.gov RI Shields, Peter/I-1644-2012; Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU NCI NIH HHS [CA-62995, CA-11535, CA01633] NR 28 TC 93 Z9 93 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 16 PY 1998 VL 75 IS 6 BP 825 EP 830 DI 10.1002/(SICI)1097-0215(19980316)75:6<825::AID-IJC2>3.0.CO;2-X PG 6 WC Oncology SC Oncology GA ZA691 UT WOS:000072391400002 PM 9506525 ER PT J AU Wang, JM Chertov, O Proost, P Li, JJ Menton, P Xu, LL Sozzani, S Mantovani, A Gong, WH Schirrmacher, V Van Damme, J Oppenheim, JJ AF Wang, JM Chertov, O Proost, P Li, JJ Menton, P Xu, LL Sozzani, S Mantovani, A Gong, WH Schirrmacher, V Van Damme, J Oppenheim, JJ TI Purification and identification of chemokines potentially involved in kidney-specific metastasis by a murine lymphoma variant: Induction of migration and NF kappa B activation SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID MONOCYTE CHEMOTACTIC PROTEIN-1; MELANOMA-CELLS; GROWTH-FACTOR; JE GENE; EXPRESSION; MECHANISMS; CHEMOATTRACTANT; PRODUCT AB The ESb-MP cell line is the subclone of a highly malignant variant of murine methylcholanthrene-induced T lymphoma, ESb, When injected in vivo, ESb-MP cells metastasize to the kidney with high frequency, whereas a non-adherent variant, ESb tells, rarely form metastatic foci in the kidney, Our previous results skewed that ESb-MP, but not ESb, cells were able to migrate in response to murine kidney-conditioned media (KCM). In an effort to characterize the tumor cell chemoattractant(s) produced by kidney cells, we found that the murine kidney mesangial cell line MES-13 released more chemotactic activity for ESb-MP cells than present in KCM. A major heparin-binding chemotactic activity was purified to homogeneity by sequential fast-performance liquid chromatography and reversed phase high-performance liquid chromatography, Amino acid sequencing of the formic acid-digested active fractions revealed that the purified protein was identical to murine MCP-1(JE) and its activity was neutralized by an anti-MCP-1(JE) antibody, Another chemokine, RANTES, was also purified from MES-13 cell supernatant. The chemotactic activity contained in the MES-13 cell supernatant and in murine KCM was neutralized in part by a combination of anti-MCP-1(JE) and anti-RANTES antibodies. We further examined the differences in the ESb-MP and ESb cells. Binding studies using a variety of radio-iodinated chemokines showed that although both ESb-MP and ESb cells expressed substantial levels of high-affinity binding sites for CC chemokines, only ESb-MP cells migrated in response to CC chemokines and these cells constitutively expressed higher levels of beta 2 integrin adhesion protein CD11b than their parental ESb cells. CC chemokines also activated NF kappa B in ESb-MP but not its ESb cells. Our results indicate that CC chemokines, selectively chemoattract and activate ESb-MP cells. Thus, locally produced chemokines, MCP-1(JE) and RANTES in particular, may contribute to the preferential metastasis of ESb-MP cells to the kidneys. (C) 1998 Wiley-Liss, Inc. C1 NCI, Div Basic Sci, Mol Immunoregulat Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Katholieke Univ Leuven, Rega Inst, B-3000 Louvain, Belgium. NCI, Lab Biochem Physiol, DBS, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Ist Ric Farmacol Mario Negri, Milan, Italy. German Canc Res Ctr, D-6900 Heidelberg, Germany. RP Wang, JM (reprint author), NCI, Div Basic Sci, Mol Immunoregulat Lab, Frederick Canc Res & Dev Ctr, Bldg 560,Room 31-38, Frederick, MD 21702 USA. EM wangji@fcrfv1.ncifcrf.gov RI Sozzani, Silvano/C-1447-2009; OI Sozzani, Silvano/0000-0002-3144-8743; Mantovani, Alberto/0000-0001-5578-236X NR 27 TC 47 Z9 50 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 16 PY 1998 VL 75 IS 6 BP 900 EP 907 DI 10.1002/(SICI)1097-0215(19980316)75:6<900::AID-IJC13>3.0.CO;2-6 PG 8 WC Oncology SC Oncology GA ZA691 UT WOS:000072391400013 PM 9506536 ER PT J AU Blagosklonny, MV El-Deiry, WS AF Blagosklonny, MV El-Deiry, WS TI Acute overexpression of wt p53 facilitates anticancer drug-induced death of cancer and normal cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID WILD-TYPE P53; MAMMARY EPITHELIAL-CELLS; DNA-DAMAGE; APOPTOSIS; ADENOVIRUS; AGENTS; GENE; CHEMOSENSITIVITY; CYTOTOXICITY; SENSITIVITY AB The relationship between chemosensitivity and p53 is currently considered from two mutually exclusive points of view: (1) wt p53 increases chemosensitivity due to apoptosis and (2) wt p53 decreases chemosensitivity due to growth arrest and DNA repair. We used p53-expressing adenovirus (Ad-p53) to directly evaluate effect of p53 on sensitivity to anticancer drugs. When p53 was expressed at sublethal levels, it sensitized cells to the DNA-damaging drugs Adriamycin, mitomycin C, actinomycin D, etoposide (VP16), cisplatin and CPT11. This sensitization was observed in cancer cell lines (N = 10) regardless of endogenous p53 status and also in normal human lung and skin fibroblasts. The degree of sensitization appeared to be greater in cancer cells with mutant p53. Normal fibroblasts required significantly higher doses of Ad-p53 to affect a drug's sensitivity partly because of their lower infectivity by adenovirus. Wt p53 not only decreased IC50 but also accelerated cell death induced by DNA-damaging drugs. In contrast, sensitization to microtubule-active drugs by p53 was shown only in a few cell lines. We conclude that exogenous wt p53 accelerates cell death induced by DNA damaging agents in both normal and cancer cells and offers no protection from anticancer drugs. (C) 1998 Wiley-Liss, Inc. C1 NCI, Med Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Dept Med, Howard Hughes Med Inst, Philadelphia, PA 19104 USA. Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. RP Blagosklonny, MV (reprint author), NCI, Med Branch, NIH, Bldg 10,Room 12N226, Bethesda, MD 20892 USA. NR 25 TC 67 Z9 69 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 16 PY 1998 VL 75 IS 6 BP 933 EP 940 DI 10.1002/(SICI)1097-0215(19980316)75:6<933::AID-IJC17>3.3.CO;2-P PG 8 WC Oncology SC Oncology GA ZA691 UT WOS:000072391400017 PM 9506540 ER PT J AU Yang, M Omura, S Bonifacino, JS Weissman, AM AF Yang, M Omura, S Bonifacino, JS Weissman, AM TI Novel aspects of degradation of T cell receptor subunits from the endoplasmic reticulum (ER) in T cells: Importance of oligosaccharide processing, ubiquitination, and proteasome-dependent removal from ER membranes SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TCR-ALPHA-PROTEINS; PRE-GOLGI DEGRADATION; ANTIGEN RECEPTOR; MONOCLONAL-ANTIBODY; RAT-LIVER; COMPLEX; PATHWAY; EXPRESSION; CALNEXIN; CHAINS AB Expression of the T cell antigen receptor (TCR) on the surface of thymocytes and mature T cells is dependent on the assembly of receptor subunits into TCRs in the endoplasmic reticulum (ER) and their successful traversal of the secretory pathway to the plasma membrane. TCR subunits that fail to exit the ER for the Golgi complex are degraded by nonlysosomal processes that have been referred to as "ER degradation". The molecular basis for the loss of the TCR CD3-delta and TCR-alpha subunits from the ER was investigated in lymphocytes. For CD3-delta, we describe a process leading to its degradation that includes trimming of mannose residues from asparagine-linked (N-linked) oligosaccharides, generation of ubiquitinated membrane-bound intermediates, and proteasome-dependent removal from the ER membrane. When either mannosidase activity or the catalytic activity of proteasomes was inhibited, loss of CD3-delta was markedly curtailed and CD3-delta remained membrane bound in a complex with CD3-epsilon. TCR-alpha was also found to be degraded in a proteasome-dependent manner with ubiquitinated intermediates. However, no evidence of a role for mannosidases was found for TCR-alpha, and significant retrograde movement through the ER membrane took place even when proteasome function was inhibited. These findings provide new insights into mechanisms employed to regulate levels of TCRs, and underscore that cells use multiple mechanisms to target proteins from the ER to the cytosol for degradation. C1 NCI, Lab Immune Cell Biol, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Kitasato Inst, Tokyo 108, Japan. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Weissman, AM (reprint author), NCI, Lab Immune Cell Biol, Div Basic Sci, NIH, 9000 Rockville Pike,Bldg 10,Rm 1B35, Bethesda, MD 20892 USA. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 55 TC 182 Z9 183 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 16 PY 1998 VL 187 IS 6 BP 835 EP 846 DI 10.1084/jem.187.6.835 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA ZD092 UT WOS:000072650600003 PM 9500786 ER PT J AU Kulig, K Nandi, D Bacik, I Monaco, JJ Vukmanovic, S AF Kulig, K Nandi, D Bacik, I Monaco, JJ Vukmanovic, S TI Physical and functional association of the major histocompatibility complex class I heavy chain alpha 3 domain with the transporter associated with antigen processing SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CYTOTOXIC LYMPHOCYTES-T; ENDOGENOUSLY SYNTHESIZED PEPTIDE; INTRACELLULAR-TRANSPORT; CELL-LINE; MOLECULES; TAP; BINDING; EXPRESSION; CALNEXIN; VIRUS AB CD8(+) T lymphocytes recognize antigens as short, MHC class I-associated peptides derived by processing of cytoplasmic proteins. The transporter associated with antigen processing translocates peptides from the cytosol into the ER lumen, where they bind to the nascent class I molecules. To date, the precise location of the class I-TAP interaction site remains unclear. We provide evidence that this site is contained within the heavy chain alpha 3 domain. Substitution of a 15 amino acid portion of the H-2D(b) alpha 3 domain (aa 219-233) with the analogous MHC class II (H-2IA(d)) beta 2 domain region (aa 133-147) results in loss of surface expression which can be partially restored upon incubation at 26 degrees C in the presence of excess peptide and beta 2-microglobulin. Mutant H-2D(b) (D(b)219-233) associates poorly with the TAP complex, and cannot present endogenously-derived antigenic peptides requiring TAP-dependent translocation to the ER. However, this presentation defect can be overcome through use of an ER targeting sequence which bypasses TAP-dependent peptide translocation. Thus, the alpha 3 domain serves as an important site of interaction (directly or-indirectly) with the TAP complex and is necessary for TAP-dependent peptide loading and class I surface expression. C1 NYU Med Ctr, Dept Pathol, Michael Heidelberger Div Immunol, New York, NY 10016 USA. NYU Med Ctr, Kaplan Comprehens Canc Ctr, New York, NY 10016 USA. Indian Inst Sci, Dept Biochem, Bangalore 560012, Karnataka, India. NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. Univ Cincinnati, Howard Hughes Med Inst, Dept Mol Genet, Cincinnati, OH 45267 USA. RP Vukmanovic, S (reprint author), NYU Med Ctr, Dept Pathol, Michael Heidelberger Div Immunol, 550 1st Ave, New York, NY 10016 USA. RI Nandi, Dipankar/A-9194-2009 FU NCI NIH HHS [P30 CA016087, 5P30 CA-16087]; NIAID NIH HHS [AI-33605] NR 48 TC 40 Z9 40 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 16 PY 1998 VL 187 IS 6 BP 865 EP 874 DI 10.1084/jem.187.6.865 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA ZD092 UT WOS:000072650600006 PM 9500789 ER PT J AU Bernacki, SH Medvedev, A Holloway, G Dawson, M Lotan, R Jetten, AM AF Bernacki, SH Medvedev, A Holloway, G Dawson, M Lotan, R Jetten, AM TI Suppression of relaxin gene expression by retinoids in squamous differentiated rabbit tracheal epithelial cells SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE relaxin; retinoic acid; squamous differentiation; trachea; epithelia; gene expression ID PREPRORELAXIN-LIKE GENE; TRANSCRIPTION FACTORS; ACID RECEPTORS; BINDING; IDENTIFICATION; PROTEINS; HORMONE; AP-1; RAT; TRANSGLUTAMINASE AB Northern blot analysis of total RNA from a variety of rabbit tissues indicated that placenta is the primary site of expression of the protein hormone relaxin (previously called SQ10) in rabbits. Relaxin was not detected by this method in other rabbit tissues, including normal trachea and several squamous tissues. However, relaxin is highly induced during squamous cell differentiation in cultured rabbit tracheal epithelial (RbTE) cells. Retinoic acid and retinoids that selectively bind to the nuclear retinoid receptors, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs), and induce RARE- or RXRE-dependent transactivation as well as repression of AP-1-dependent transactivation, were all effective in suppressing relaxin expression. In addition, the retinoid SR11302, which exhibits only anti-AP-1 activity but does not induce RARE- or RXRE-dependent transactivation, was also able to inhibit relaxin expression. These results suggest that the suppression of relaxin expression is related to the anti-AP-1 activity of retinoids. To determine whether the relaxin gene is regulated by retinoids at the level of transcription, a 4.3 kb fragment of the 5' flanking region of the rabbit relaxin gene was cloned and analyzed. This regulatory region included a classic TATA-box as well as consensus sequences for several transcription factors, including CREB, NF-kappa B and AP-1. The ability of the 4.3 kb regulatory region to control the transcription of a luciferase reporter gene was analyzed in transiently transfected, squamous-differentiated RbTE cells. The results demonstrated that this regulatory region caused strong transactivation of the reporter gene. This transactivation was inhibited by retinoic acid, suggesting retinoid control at the transcriptional level. Deletion analysis indicated that multiple regulatory elements are involved in the regulation of relaxin gene expression during squamous differentiation as well as in the suppression by retinoids. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 NIEHS, Cell Biol Sect, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Sch Med, Cyst Fibrosis Res & Treatment Ctr, Chapel Hill, NC 27599 USA. SRI Int, Retinoid Program, Menlo Park, CA 94025 USA. Univ Texas, MD Anderson Cancer Ctr, Dept Tumor Biol, Houston, TX 77030 USA. RP Jetten, AM (reprint author), NIEHS, Cell Biol Sect, Pulm Pathobiol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM jetten@niehs.nih.gov OI Jetten, Anton/0000-0003-0954-4445 NR 58 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD MAR 16 PY 1998 VL 138 IS 1-2 BP 115 EP 125 DI 10.1016/S0303-7207(98)00013-6 PG 11 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA ZV992 UT WOS:000074362900011 PM 9685220 ER PT J AU Everhart, JE Byrd-Holt, D Sonnenberg, A AF Everhart, JE Byrd-Holt, D Sonnenberg, A TI Incidence and risk factors for self-reported peptic ulcer disease in the United States SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE duodenal ulcer; incidence; peptic ulcer; risk factors ID DUODENAL-ULCER; COPENHAGEN-COUNTY; GASTRIC-ULCER; SMOKING; COHORT; PREVALENCE; NORWAY AB Incidence and risk factors for peptic ulcer disease in the United States have not been well defined, During the 1989 National Health Interview Survey, a population-based sample of 42,392 individuals responded to questions regarding doctor-diagnosed ulcers with confirmation by either an upper gastrointestinal series or endoscopy, Ulcers present during the previous 12 months were considered either incident ulcers if diagnosed during this period or chronic active ulcers if diagnosed more than 12 months before the interview. The incidence of ulcers over the year prior to the interview was 5.27 per 1,000 adults, Whereas incident duodenal ulcer cases represented only 2.4 percent of all persons with a history of duodenal ulcer, the corresponding value for gastric ulcer was 8.7 percent, Risk factors for incident ulcers included increasing age, lower income and educational attainment, and musculoskeletal pain or headache, These were similar to risk factors for chronic active ulcers, except smoking was an additional important risk factor for chronic active ulcers. Thus, incident peptic ulcers are common in the United States but represent a small proportion of persons with a history of ulcer disease. Smoking may be a stronger risk factor for chronic ulcers than for new ulcers. C1 NIDDK, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. Social & Sci Syst, Bethesda, MD USA. Univ New Mexico, Albuquerque, NM 87131 USA. RP Everhart, JE (reprint author), NIDDK, Div Digest Dis & Nutr, Natcher Bldg,Room 6AN-12J,45 Ctr Dr MSC 6600, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [N01-DK-1-2282, N01-DK-6-2220] NR 32 TC 32 Z9 33 U1 1 U2 2 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 15 PY 1998 VL 147 IS 6 BP 529 EP 536 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZC538 UT WOS:000072590400004 PM 9521179 ER PT J AU Cocco, P Ward, MH AF Cocco, P Ward, MH TI Re: "Occupational risk factors for gastric cancer: An overview - Two authors reply SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter ID RUBBER WORKERS; MORTALITY; INDUSTRY; EXPOSURE; COHORT C1 Univ Cagliari, Ist Med Lavoro, I-09124 Cagliari, Italy. NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Cocco, P (reprint author), Univ Cagliari, Ist Med Lavoro, I-09124 Cagliari, Italy. NR 23 TC 0 Z9 0 U1 1 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 15 PY 1998 VL 147 IS 6 BP 609 EP 610 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZC538 UT WOS:000072590400018 ER PT J AU Basser, PJ Schneiderman, R Bank, RA Wachtel, E Maroudas, A AF Basser, PJ Schneiderman, R Bank, RA Wachtel, E Maroudas, A TI Mechanical properties of the collagen network in human articular cartilage as measured by osmotic stress technique SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE human cartilage; hydration; collagen network; proteoglycan; osmotic pressure; osteoarthritis; degeneration; connective tissue; tension; swelling ID FEMORAL-HEAD CARTILAGE; PERFORMANCE LIQUID-CHROMATOGRAPHY; CHEMICAL COMPOSITION; SWELLING PRESSURE; HIP JOINT; PROTEOGLYCANS; PACKING; TISSUES; FORCES; ACID AB We have used an isotropic osmotic stress technique to assess the swelling pressures of human articular cartilage over a wide range of hydrations in order to determine from these measurements, for the first time, the tensile stress in the collagen network, P-c, as a function of hydration. Osmotic stress was applied by means of calibrated solutions of polyethylene glycol, Calculations of osmotic stress were based on the balance, at equilibrium, between the applied stress, the collagen stress, and the proteoglycan osmotic pressure, pi(PG), acting within the extrafibrillar matrix compartment. P-c vs hydration was determined for several normal human samples, both native and trypsin-treated, and for cartilage from one osteoarthritic (OA) joint. We found that for normal cartilage the collagen network. does not become "limp" until the volume of cartilage has decreased by 20-25% of its initial value and that its contribution to the balance of forces in cartilage therefore must be taken into account over a much wider range of hydrations than was previously thought. For normal cartilage, the P-c vs hydration curves exhibit a steep increase with increasing hydration; trypsin treatment does not change their slope, showing that PC; concentration does not influence the inherent stiffness of the collagen network. By contrast, the curves for OA specimens are considerably shallower and displaced to higher hydrations, Our findings thus highlight the role of the stiffness of the collagen network in limiting hydration in normal cartilage and ensuring a high PG concentration in the matrix, which is essential for effective load-bearing and is lost in OA. (C) 1998 Academic Press. C1 Technion Israel Inst Technol, Dept Biomed Engn, Julius Silver Inst Biomed Sci, IL-32000 Haifa, Israel. TNO Prevent & Hlth, Div Vasc & Connect Tissue Res, Leiden, Netherlands. NIH, Natl Ctr Res Resources, Biomed Engn & Instrumentat Program, Bethesda, MD USA. Weizmann Inst Sci, Chem Serv Unit, IL-76100 Rehovot, Israel. RP Maroudas, A (reprint author), Technion Israel Inst Technol, Dept Biomed Engn, Julius Silver Inst Biomed Sci, IL-32000 Haifa, Israel. EM alice@biomed.technion.ac.il RI Basser, Peter/H-5477-2011 NR 57 TC 175 Z9 177 U1 5 U2 18 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAR 15 PY 1998 VL 351 IS 2 BP 207 EP 219 DI 10.1006/abbi.1997.0507 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZD688 UT WOS:000072712900009 PM 9515057 ER PT J AU Roberts, SJ Petropavlovskaja, M Chung, KN Knight, CB Elwood, PC AF Roberts, SJ Petropavlovskaja, M Chung, KN Knight, CB Elwood, PC TI Role of individual N-linked glycosylation sites in the function and intracellular transport of the human alpha folate receptor SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE human alpha folate receptor; glycosylation; mutagenesis ID BINDING-PROTEIN; KB CELLS; ENDOPLASMIC-RETICULUM; DIRECTED MUTAGENESIS; HORMONE RECEPTOR; LIGAND-BINDING; AMINO-ACID; GLYCOPROTEIN; CDNA; OLIGOSACCHARIDES AB Glycosylation is a structural feature of all three isoforms of the human folate receptor. We have used site-directed mutagenesis to study the role of individual glycosylation sites in the assembly and function of the alpha isoform of the human folate receptor (alpha hFR), Three potential N-linked glycosylation sites in the alpha hFR sequence were disrupted by conservative mutation of the S or T residues in the consensus sequence (N-X-S/T) to A or V, respectively. Constructs with the single mutations S-71 --> A (alpha hFR(-1)), T-163 --> V (alpha hFR(-2)), and S-203 --> A (alpha hFR(-3)); the double mutation S-71 --> A/S-203 --> A (alpha hFR(-1-3)); and the triple mutation S-71 --> A/S-203 --> A/T-163 --> V ((alpha hFR(-1-2-3)) were stably transfected into Chinese hamster ovary (CHO) cells. The proteins produced in CHO cells by the mutated cDNAs have apparent molecular weights that are reduced relative to the wild type and are consistent with the loss of carbohydrate residues. The triple mutant, which lacks all three consensus glycosylation sites, yields protein that comigrates with the enzymatically deglycosylated native protein, Determinations of the KD for folic acid by Scatchard analyses of the glycosylation mutants indicate that folic acid binding affinity is not significantly affected in the single mutants alpha FR-1 and alpha hFR(-2). However, in the single mutant, alpha hFR(-3), and the double mutant, alpha hFR(-1-3), folic acid binding affinity is respectively 2.7- and 3.5-fold lower than that in wild type, Deglycosylation by mutation of all three consensus sites (alpha hFR(-1-2-3)) eliminates both folic acid binding and cell surface expression. In contrast, enzymatic deglycosylation of purified wild-type alpha hFR with endoglycosidase F does not significantly affect folate binding affinity. Thus, while carbohydrate residues are not essential for the folate binding activity of the mature folate receptor, at least one of the three core glycosylated residues is necessary for the synthesis of alpha hFR in its active conformation. (C) 1998 Academic Press. C1 NCI, DCS, Med Branch, Sect Expt Hematol,NIH, Bethesda, MD 20892 USA. RP Elwood, PC (reprint author), NCI, DCS, Med Branch, Sect Expt Hematol,NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM pce@helix.nih.gov NR 34 TC 14 Z9 14 U1 0 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAR 15 PY 1998 VL 351 IS 2 BP 227 EP 235 DI 10.1006/abbi.1997.0551 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZD688 UT WOS:000072712900011 PM 9515058 ER PT J AU Gunther, MR Tschirret-Guth, RA Witkowska, HE Fann, YC Barr, DP de Montellano, PRO Mason, RP AF Gunther, MR Tschirret-Guth, RA Witkowska, HE Fann, YC Barr, DP de Montellano, PRO Mason, RP TI Site-specific spin trapping of tyrosine radicals in the oxidation of metmyoglobin by hydrogen peroxide SO BIOCHEMICAL JOURNAL LA English DT Article ID SPERM WHALE MYOGLOBIN; PROTEIN RADICALS; CROSS-LINKING; CYTOCHROME-C; TRYPTOPHAN; IDENTIFICATION; EPOXIDATION; TYR-151; STYRENE; HYDROPEROXIDE AB The reaction between metmyoglobin and hydrogen peroxide produces both a ferryl-oxo heme and a globin-centred radical(s) from the tao oxidizing equivalents of the hydrogen peroxide. Evidence has been presented for localization of the globin-centred radical on one tryptophan residue and tyrosines 103 and 151. When the spin-trapping agent 5,5-dimethyl-1-pyrroline N-oxide (DMPO) is included in the reaction mixture, a radical adduct has been detected, but the residue at which that adduct is formed has not been determined. Replacement of either tryptophans 7 and 14 or tyrosines 146 and 151 with phenylalanine has no effect on the formation of DMPO adduct in the reaction with hydrogen peroxide. When tyrosine 103 is replaced with phenylalanine, however, only DMPOX, a product of the oxidation of the spin-trap, is detected. Tyrosine-103 is, therefore, the site of radical adduct formation with DMPO. The spin trap 2-methyl-2-nitrosopropane (MNP), however: forms radical adducts with any recombinant sperm whale metmyoglobin that contains either tyrosine 103 or 151. Detailed spectral analysis of the DMPO and MNP radical adducts of isotopically substituted tyrosine radical yield complete structural determinations. The multiple sites of trapping support a model in which the unpaired electron density is spread over a number of residues in the population of metmyoglobin molecules, at least some of which are in equilibrium with each other. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. RP Gunther, MR (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. FU NCRR NIH HHS [RR06505]; NIDDK NIH HHS [DK30297]; NIGMS NIH HHS [GM32488] NR 35 TC 123 Z9 124 U1 0 U2 5 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAR 15 PY 1998 VL 330 BP 1293 EP 1299 PN 3 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZG519 UT WOS:000073011800031 PM 9494099 ER PT J AU Kumar, A Dhawan, S Hardegen, NJ Aggarwal, BB AF Kumar, A Dhawan, S Hardegen, NJ Aggarwal, BB TI Curcumin (diferuloylmethane) inhibition of tumor necrosis factor (TNF)-mediated adhesion of monocytes to endothelial cells by suppression of cell surface expression of adhesion molecules and of nuclear factor-kappa B activation SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE curcumin; adhesion proteins; NF-kappa B; TNF; endothelial cells ID E-SELECTIN EXPRESSION; GENE-EXPRESSION; DIETARY CURCUMIN; TRANSCRIPTIONAL REGULATION; COLON CARCINOGENESIS; PROTEIN-KINASE; IMMUNE-SYSTEM; CYTOKINES; INDUCTION; ALTERS AB Recruitment of leukocytes by endothelial cells and their subsequent migration from the vasculature into the tissue play major roles in inflammation In the present study, we investigated the effect of curcumin, an antiinflammatory agent, on the adhesion of monocytes to human umbilical vein endothelial cells (EC). Treatment of EC with tumor necrosis factor (TNF) for 6 hr augmented the adhesion of monocytes to EC, and this adhesion was due to increased expression of intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1). Pretreatment of EC for I hr with curcumin completely blocked their adhesion to monocytes, as well as the cell surface expression of ICAM-1, VCAM-1, and ELAM-1 in EC. Although curcumin inhibited adhesion even when administered 1 hr after TNF treatment, maximum inhibition occurred when added either 1 hr before or at the same time as TNF. As the induction of various adhesion molecules by TNF requires activation of the transcription factor NF-kappa B, the effect of curcumin on the activation of this factor in the EC was also investigated. A 30-min treatment with TNF activated NF-kappa B; the activation was inhibited in a concentration-dependent manner by pretreatment with curcumin, indicating that NF-kappa B inhibition may play a role in the suppression of expression of adhesion molecules in EC. Our results demonstrate that the antiinflammatory properties of curcumin may be attributable, in part, to inhibition of leukocyte recruitment. (C) 1998 Elsevier Science Inc. C1 Univ Texas, MD Anderson Cancer Ctr, Dept Mol Oncol, Cytokine Res Sect, Houston, TX 77030 USA. US FDA, Ctr Biol Evaluat & Res, Lab Immunochem, Div Transfus Transmitted Dis, Bethesda, MD 20892 USA. NIDR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Aggarwal, BB (reprint author), Univ Texas, MD Anderson Cancer Ctr, Dept Mol Oncol, Cytokine Res Sect, Houston, TX 77030 USA. RI Aggarwal, Bharat/G-3388-2013 NR 53 TC 161 Z9 171 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAR 15 PY 1998 VL 55 IS 6 BP 775 EP 783 DI 10.1016/S0006-2952(97)00557-1 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZC895 UT WOS:000072629800008 PM 9586949 ER PT J AU Carrier, F Zhan, QM Alamo, I Hanaoka, F Fornace, AJ AF Carrier, F Zhan, QM Alamo, I Hanaoka, F Fornace, AJ TI Evidence for distinct kinase-mediated pathways in gadd gene responses SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE gadd genes; DNA damage; kinases; ionizing radiation ID DNA-DAMAGING AGENTS; IONIZING-RADIATION; CELL-CYCLE; TYROSINE KINASES; PROTEIN-KINASES; MAMMALIAN-CELLS; NUCLEAR SIGNAL; GROWTH ARREST; INDUCTION; RNA AB We have evaluated the role of various protein kinases on the induction of the gadd (growth arrest and DNA damage inducible) genes, using a panel of protein kinase inhibitors. Our data indicate that three different stress response pathways mediating gadd gene induction are most likely regulated by different protein kinases or combinations of protein kinases. The protein kinase inhibitor staurosporine and the temperature sensitive (ts) p34(cdc2) mutant reduced induction by the alkylating agent methylmethane sulfonate (MMS) of the rodent gadd45 and gadd153 genes. However, staurosporine had no effect of the ionising radiation (IR) induction of the human GADD45. Caffeine and 2-aminopurine, on the other hand, completely blocked this IR induction. Suramin, an antitumor drug that interferes with the interaction of growth factors with their receptors, inhibited the UV radiation induction of GADD45 and GADD153 but had no effect on the MMS and IR pathways. Elevated expression of gadd45 by medium depletion (starvation) was partially reduced by the addition of either genistein or tyrphostin, two protein tyrosine kinase inhibitors, while gadd153 was affected by tyrphostin only. Two inhibitors acting preferentially on cAMP-dependent protein kinase (PKA), N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide, HCl (H8) and protein kinase inhibitor (PKI), also had a moderate effect on the medium depletion-induced levels of both gadd genes. Thus, these varied effects of inhibitors on gadd gene responses point to important differences in the pathways controlling these responses. (C) 1998 Elsevier Science Inc. C1 NCI, Mol Pharmacol Lab, DTP, DCT,NIH, Bethesda, MD 20892 USA. RP Carrier, F (reprint author), NCI, Mol Pharmacol Lab, DTP, DCT,NIH, Bldg 37 Room 5C09, Bethesda, MD 20892 USA. RI Carrier, France/C-3063-2008; Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 35 TC 21 Z9 22 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAR 15 PY 1998 VL 55 IS 6 BP 853 EP 861 DI 10.1016/S0006-2952(97)00592-3 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZC895 UT WOS:000072629800017 PM 9586958 ER PT J AU Yang, TJ Shou, M Korzekwa, KR Gonzalez, FJ Gelboin, HV Yang, SK AF Yang, TJ Shou, M Korzekwa, KR Gonzalez, FJ Gelboin, HV Yang, SK TI Role of cDNA-expressed human cytochromes P450 in the metabolism of diazepam SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE diazepam metabolism; human liver microsomes; cDNA expression; cytochrome P450; high-performance liquid chromatography ID HUMAN LIVER-MICROSOMES; HEPATIC CYTOCHROME-P450; MUTAGEN ACTIVATION; N-DEMETHYLATION; VACCINIA VIRUS; EPOXIDE; ENZYMES; CELLS; AGE; RAT AB The metabolic conversion of diazepam (DZ) to temazepam (TMZ, a C3-hydroxylation product of DZ) and N-desmethyldiazepam (NDZ, an N1-demethylation product of DZ) was studied using cDNA-expressed human cytochrome P450 (CYP) isozymes 1A2, 2B6, 2C8, 2C9, 2C9(R144C), 2E1, 3A4, and 3A5 and human liver microsomes from five organ donors. Of the CYPs examined, 3A5, 3A4, and 2B6 exhibited the highest enzymatic activities with turnovers ranging from 7.5 to 12.5 nmol of product formed/min/nmol for the total metabolism of DZ, while 2C8, 2C9, and 2C9(R144C) showed lesser and moderate activities. 1A2 and 2E1 produced insignificant amounts of metabolites of DZ. The regioselectivity of CYPs was determined, and 2B6 was found to catalyze exclusively and 2C8, 2C9, and 2C9(R144C) preferentially the N1-demethylation of DZ to form NDZ. 3A4 and 3A5 catalyzed primarily the C3-hydroxylation of DZ, which was more extensive than the N1-demethylation. The ratios of TMZ to NDZ farmed in the metabolism of DZ by 3A4 and 3A5 were approximately 4:1. Enzyme kinetic studies indicated that 2B6- and 2C9-catalyzed DZ metabolism followed Michaelis-Menten kinetics, whereas 3A4 and 3A5 displayed atypical and non-linear curves in Lineweaver-Burk plots. Human liver microsomes converted DZ to both TMZ and NDZ at a ratio of 2:1. Our results suggest that hepatic CYP3A, 2C, and 2B6 enzymes have an important role In the metabolism of DZ by human liver. (C) 1998 Elsevier Science Inc. C1 Merck Res Labs, Dept Drug Metab, W Point, PA 19486 USA. Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Pharmacol, Bethesda, MD 20814 USA. NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Med Ctr, Dept Clin Pharmacol, Pittsburgh, PA 15261 USA. RP Shou, M (reprint author), Merck Res Labs, Dept Drug Metab, WP26A-2044, W Point, PA 19486 USA. NR 28 TC 43 Z9 44 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAR 15 PY 1998 VL 55 IS 6 BP 889 EP 896 DI 10.1016/S0006-2952(97)00558-3 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZC895 UT WOS:000072629800021 PM 9586962 ER PT J AU Broocks, A Little, JT Martin, A Minichiello, MD Dubbert, B Mack, C Tune, L Murphy, DL Sunderland, T AF Broocks, A Little, JT Martin, A Minichiello, MD Dubbert, B Mack, C Tune, L Murphy, DL Sunderland, T TI The influence of ondansetron and m-chlorophenylpiperazine on scopolamine-induced cognitive, behavioral, and physiological responses in young healthy controls SO BIOLOGICAL PSYCHIATRY LA English DT Article DE cognitive performance; scopolamine; ondansetron; m-chlorophenylpiperazine ID OBSESSIVE-COMPULSIVE DISORDER; META-CHLOROPHENYLPIPERAZINE; ACETYLCHOLINE-RELEASE; SEROTONIN AGONIST; 5-HT3 RECEPTORS; MEDIATE INHIBITION; ALZHEIMERS-DISEASE; NEUROENDOCRINE; ANTAGONISTS; MEMORY AB Background: There is evidence from animal and human experiments that learning and memory come under the separate influence of both cholinergic and serotonergic pathways. We were interested in learning whether serotonergic drugs could attenuate or exacerbate the memory-impairing effects of anticholinergic blockade in humans. Methods: The selective serotonin 5-HT3 receptor antagonist ondansetron (0.15 mg/kg IV) and the serotonergic agent m-chlorophenylpiperazine (m-CPP; 0.08 mg/kg IV) were administered in combination with the anticholinergic agent scopolamine (0.4 mg PO) and compared to scopolamine alone in 10 young, healthy volunteers. Testing occurred on three separate days. Results: As expected, IV administration of scopolamine induced significant impairments in episodic memory and processing speed; however, these scopolamine-induced cognitive deficits were not attenuated by pretreatment with IV ondansetron (0.15 mg/kg), nor were they exacerbated by administration of IV m-CPP (0.8 mg/kg) in addition to scopolamine; however, administration of IV m-CPP was followed by a significant increase of self-rated functional impairment, altered self-reality, and dysphoria ratings, and scopolamine's effect on pupil size was potentiated. Conclusions: Together, these results suggest that in young, healthy volunteers scopolamine-induced changes of cognitive performance are only minimally modulated by the serotonergic effects on ondansetron and m-CPP. Further studies with older controls are needed to test whether these findings may be influenced by age. Published 1998 Society of Biological Psychiatry. C1 NIMH, Geriatr Psychiat Branch, NIH, Ctr Clin, Bethesda, MD 20892 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. Goettingen Univ, Dept Psychiat, Goettingen, Germany. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. RP Sunderland, T (reprint author), NIMH, Geriatr Psychiat Branch, NIH, Ctr Clin, 10-3D41,10 Ctr Dr,MSC 1264, Bethesda, MD 20892 USA. RI martin, alex/B-6176-2009 NR 48 TC 23 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 15 PY 1998 VL 43 IS 6 BP 408 EP 416 DI 10.1016/S0006-3223(97)00388-0 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZB552 UT WOS:000072484000004 PM 9532345 ER PT J AU Pickworth, W Fant, R Goffman, A Henningfield, J AF Pickworth, W Fant, R Goffman, A Henningfield, J TI Cranial electrostimulation therapy - Response SO BIOLOGICAL PSYCHIATRY LA English DT Letter C1 NIDA, Div Intramural Res, Addict Res Ctr, NIH, Baltimore, MD 21224 USA. RP Pickworth, W (reprint author), NIDA, Div Intramural Res, Addict Res Ctr, NIH, Baltimore, MD 21224 USA. NR 3 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 15 PY 1998 VL 43 IS 6 BP 468 EP 469 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZB552 UT WOS:000072484000015 ER PT J AU Viswanatha, DS Chen, IM Liu, PP Slovak, ML Rankin, C Head, DR Willman, CL AF Viswanatha, DS Chen, IM Liu, PP Slovak, ML Rankin, C Head, DR Willman, CL TI Characterization and use of an antibody detecting the CBF beta-SMMHC fusion protein in inv(16)/t(16;16)-associated acute myeloid leukemias SO BLOOD LA English DT Article ID ACUTE MYELOMONOCYTIC LEUKEMIA; ACUTE NONLYMPHOCYTIC LEUKEMIA; ABNORMAL MARROW EOSINOPHILS; ACUTE MYELOGENOUS LEUKEMIA; CHROMOSOME-16 ABNORMALITY; INV(16)(P13Q22); INVERSION; GENE; TRANSCRIPTS; CBFB-MYH11 AB The inv(16)(p13q22) and t(16;16)(p13;q22) cytogenetic abnormalities occur commonly in acute myeloid leukemia (AML), typically associated with French-American-British (FAB) AML-M4Eo subtype. Reverse transcriptase-polymerase chain reaction (RT-PCR) techniques have been recently developed to detect the presence of several variants of the resultant CBFB-MYH11 fusion gene that encodes a CBF beta-smooth muscle myosin heavy chain (SMMHC) fusion protein. We have now determined the clinical use of a polyclonal antibody [anti-inv(16) Ab] directed against a junctional epitope of the most common type of CBF beta-SMMHC fusion protein (type A), which is present in 90% of inv(16)/t(16;16) AML cases. Using flow cytometry, reproducible methods were developed for detection of CBF beta-SMMHC proteins in permeabilized cells; flow cytometric results were then correlated with cytogenetics and RT-PCR detection methods. In an analysis of 42 leukemia cases with various cytogenetic abnormalities and several normal controls, the anti-inv(16) Ab specifically detected all 23 cases that were cytogenetically positive for inv(16) or t(16;16), including a single AML case that was RT-PCR-negative. In addition to detecting all type A fusions, the anti-inv(18) Ab also unexpectedly identified the type C and type D CBF beta-SMMHC fusion proteins. Molecular characterization of one RT-PCR-positive and Ab-positive t(16;16) case with a non-type A product showed a novel previously unreported CBFB-MYH11 fusion (CBFB nt 455-MYH11 nt 1893). Flow cytometric results were analyzed using the Kolmogorov-Smirnov statistic D-value and the median value for positive samples was 0.65 (range, 0.35 to 0.77) versus 0.07 (range, -0.21 to 0.18) in the negative group (P < .0001). The overall concordance between cytogenetics and RT-PCR was 97%, whereas the concordance between flow cytometry and cytogenetics was 100%. Thus, using the anti-inv(16) Ab, all cytogenetically positive and RT-PCR-positive AML cases with inv(ls) or t(16;16) could be rapidly identified. This study demonstrates the use of this antibody as an investigational tool in inv(16)/t(16;16) AML and suggests that the development of such reagents may have potential clinical diagnostic use. (C) 1998 by The American Society of Hematology. C1 Univ New Mexico, Sch Med, Dept Pathol & Canc Ctr, Albuquerque, NM 87131 USA. NIH, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. SW Oncol Grp, Ctr Stat, Seattle, WA USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. RP Willman, CL (reprint author), SWOG Operat Off, 14908 Omicron Dr, San Antonio, TX 78245 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X FU NCI NIH HHS [U01 CA32102] NR 42 TC 15 Z9 16 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 1998 VL 91 IS 6 BP 1882 EP 1890 PG 9 WC Hematology SC Hematology GA ZB156 UT WOS:000072442000007 PM 9490670 ER PT J AU Kanegane, H Bhatia, K Gutierrez, M Kaneda, H Wada, T Yachie, A Seki, H Arai, T Kagimoto, S Okazaki, M Oh-ishi, T Moghaddam, A Wang, F Tosato, G AF Kanegane, H Bhatia, K Gutierrez, M Kaneda, H Wada, T Yachie, A Seki, H Arai, T Kagimoto, S Okazaki, M Oh-ishi, T Moghaddam, A Wang, F Tosato, G TI Syndrome of peripheral blood T-cell infection with Epstein-Barr virus (EBV) followed by EBV-positive T-cell lymphoma SO BLOOD LA English DT Article ID CD3-NEGATIVE LYMPHOPROLIFERATIVE DISEASE; POLYMERASE CHAIN-REACTION; GRANULAR LYMPHOCYTES; HUMAN THYMOCYTES; VIRAL-DNA; HODGKINS-DISEASE; EXPRESSION; LINE; ASSOCIATION; CARCINOMA AB The role of Epstein-Barr virus (EBV) in the pathogenesis of severe, chronic active EBV infection and its complications is unclear. We investigated two Japanese patients diagnosed with severe, chronic active EBV infection who subsequently developed EBV-positive T-cell lymphoma. The patients displayed abnormally high antibody titers to EBV antigens, and had evidence of peripheral blood CD4(+) T cell infection with EBV, 19 months and 3 months, respectively, before the diagnosis of EBV-positive T-cell lymphoma. The lymphomas were infected with monoclonal EBV and expressed the EBV latency genes EBNA-1, LMP-1, and LMP-2. Genetic studies showed that the virus detected in the T-cell lymphoma was indistinguishable, with respect to type and previously defined LMP-1 and EBNA-1 gene variations, from virus detected in the peripheral blood T cells 19 months earlier. These studies support an important pathogenetic role of T cell infection with EBV in chronic active EBV infection and in the EBV-positive T-cell lymphoma that followed. C1 Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NCI, NIH, Bethesda, MD 20892 USA. Kanazawa Univ, Sch Med, Kanazawa, Ishikawa 920, Japan. Saitama Childrens Med Ctr, Iwatsuki, Saitama, Japan. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Infect Dis, Boston, MA 02115 USA. RP Tosato, G (reprint author), Ctr Biol Evaluat & Res, Bldg 29A,Room 2D16,HFM-535,1401 Rockville Pike, Rockville, MD 20852 USA. RI Yachie, Akihiro/C-4660-2015 NR 40 TC 85 Z9 87 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 1998 VL 91 IS 6 BP 2085 EP 2091 PG 7 WC Hematology SC Hematology GA ZB156 UT WOS:000072442000031 PM 9490694 ER PT J AU De, SK Venkateshan, CNS Seth, P Gajdusek, DC Gibbs, CJ AF De, SK Venkateshan, CNS Seth, P Gajdusek, DC Gibbs, CJ TI Adenovirus-mediated human immunodeficiency virus-1 nef expression in human monocytes/macrophages and effect of nef on downmodulation of Fc gamma receptors and expression of monokines SO BLOOD LA English DT Review ID TUMOR-NECROSIS-FACTOR; MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I MOLECULES; INFECTED MONOCYTIC CELLS; BLOOD MONONUCLEAR-CELLS; DOWN-REGULATION; TRANSFERRIN RECEPTOR; ENVELOPE PROTEIN; GENE-TRANSFER; FACTOR-ALPHA AB To characterize the effect of human immunodeficiency virus-1 (HIV-1) nef expression in human monocytes/macrophage (HMO) and U937 on the levels of Fc gamma Rs, HLA antigens, and monokines, elutriated HMOs and U937 cells were transfected with an adenovirus-mediated Nef expression system. Nef-expressing cells downmodulated Fc gamma RI, Fc gamma RII, and upregulated HLA class I molecules. Nef-expressing HMOs, treated with lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA), overexpressed tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and IL-10. However, IL-6 was induced by LPS and inhibited by PMA. Additionally, a subpopulation of Nef-expressing HMOs underwent apoptosis. Our data suggest that HIV-1 nef downmodulated Fc gamma Rs in myeloid cells in a manner similar to that previously reported for its effect on CD4(+) in T cells. (C) 1998 by The American Society of Hematology. C1 NIDR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Treatment, Med Branch, NIH, Bethesda, MD 20892 USA. RP De, SK (reprint author), NIDR, Oral Infect & Immun Branch, NIH, Room 232,Bldg 30, Bethesda, MD 20892 USA. NR 105 TC 25 Z9 28 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 1998 VL 91 IS 6 BP 2108 EP 2117 PG 10 WC Hematology SC Hematology GA ZB156 UT WOS:000072442000034 PM 9490697 ER PT J AU Duncan, WC Johnson, KA Sutin, E Wehr, TA AF Duncan, WC Johnson, KA Sutin, E Wehr, TA TI Disruption of the activity-rest cycle by MAOI treatment: Dependence on light and a secondary visual pathway to the circadian pacemaker SO BRAIN RESEARCH BULLETIN LA English DT Article DE affective illness; depression; clorgyline; intergeniculate leaflet; sleep-wake; lateral geniculate nucleus; suprachiasmatic nucleus ID MONOAMINE-OXIDASE INHIBITORS; PHASE-SHIFTS; RETINOHYPOTHALAMIC PROJECTION; SEROTONERGIC AGONISTS; FUNCTIONAL-ANALYSIS; CHRONIC CLORGYLINE; NOCTURNAL RODENTS; ACTIVITY RHYTHMS; CONSTANT LIGHT; GOLDEN-HAMSTER AB The disruptive effects on the activity-rest cycle of the monoamine oxidase inhibitor (MAOI) clorgyline and of continuous light were examined in Syrian hamsters, When administered in dim and moderate light intensities, clorgyline delayed the daily onset of wheel-running. When administered in bright light, it dissociated the circadian rhythm of wheel-running. This dissociation was prevented by lesions of the intergeniculate leaflet of the ventral lateral geniculate nucleus, Constant darkness restored the circadian rhythm of wheel-running in hamsters with disrupted circadian rhythms, The phase of the restored rhythm of wheel-running was shifted 6-12 h later than the phase of wheel-running prior to dissociation, Our results suggest that MAOI treatment weakens the coupling between oscillators that comprise the circadian pacemaker, and augments the disruptive effects of continuous light acting via the intergeniculate leaflet region of the ventral lateral geniculate nucleus, These effects on the circadian pacemaker may be responsible for disruptions of the sleep-wake cycle that occur as side effects when MAOIs are used clinically to treat depression and might play a role in the induction of mania and rapid cycling by antidepressants. Published 1998 Elsevier Science Inc. C1 NIMH, Clin Psychobiol Branch, NIH, Bethesda, MD 20892 USA. RP Duncan, WC (reprint author), NIMH, Clin Psychobiol Branch, NIH, Bethesda, MD 20892 USA. NR 39 TC 7 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD MAR 15 PY 1998 VL 45 IS 5 BP 457 EP 465 DI 10.1016/S0361-9230(97)00383-3 PG 9 WC Neurosciences SC Neurosciences & Neurology GA ZG373 UT WOS:000072995100004 PM 9570715 ER PT J AU Groves, FD Travis, LB Devesa, SS Ries, LAG Fraumeni, JF AF Groves, FD Travis, LB Devesa, SS Ries, LAG Fraumeni, JF TI Waldenstrom's macroglobulinemia - Incidence patterns in the United States, 1988-1994 SO CANCER LA English DT Article DE Waldenstrom's macroglobulinemia; epidemiology; incidence; age-adjusted; surveillance, epidemiology, and end results (SEER) program ID HAIRY-CELL LEUKEMIA; FOLLOW-UP; EPIDEMIOLOGY; INFECTION; FAMILY; GENE AB BACKGROUND. There are few data describing the epidemiologic aspects of Waldenstrom's macroglobulinemia (WM), a rare lymphoplasmaproliferative disorder. METHODS. The authors evaluated the incidence of WM reported in 11 population-based cancer registries in the U.S. RESULTS. A total of 624 cases were diagnosed between January 1, 1988 (when WM became reportable) and December 31, 1994. Age-adjusted incidence rates for WM (per 1 million person-years at risk) were 3.4 among males and 1.7 among females. The rates increased sharply with age, from 0.1 at age < 45 years to 36.3 at age 75+ years (males) and from 0.1 at age < 45 years to 16.4 at age 75+ years (females). The rates for WM were comparable to those for hairy cell leukemia, but considerably lower than those for multiple myeloma or chronic lymphocytic leukemia. Some geographic variation was evident, with age-adjusted rates among white males ranging from 2.2-7.8 across registries. There was no significant change in rates over the 7-year study period (P > 0.05). The markedly higher rates for WM among whites than blacks stand in contrast to multiple myeloma, which occurs twice as often among blacks. CONCLUSIONS. This survey provides new data regarding the incidence patterns of WM in the U.S. However, further epidemiologic studies with biomarkers are needed to define the environmental, genetic, immunologic, and viral determinants of this rare but distinctive disorder. (C) 1998 American Cancer Society. C1 NCI, Dept Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Prevent & Control, NIH, Bethesda, MD 20892 USA. RP Groves, FD (reprint author), NCI, Dept Canc Epidemiol & Genet, NIH, Execut Plaza N,Room 431-C,6310 Execut Blvd, Bethesda, MD 20892 USA. NR 20 TC 101 Z9 103 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 0008-543X J9 CANCER JI Cancer PD MAR 15 PY 1998 VL 82 IS 6 BP 1078 EP 1081 PG 4 WC Oncology SC Oncology GA ZA556 UT WOS:000072376400010 PM 9506352 ER PT J AU Strickler, HD Burk, R Shah, K Viscidi, R Jackson, A Pizza, G Bertoni, F Schiller, JT Manns, A Metcalf, R Qu, WM Goedert, JJ AF Strickler, HD Burk, R Shah, K Viscidi, R Jackson, A Pizza, G Bertoni, F Schiller, JT Manns, A Metcalf, R Qu, WM Goedert, JJ TI A multifaceted study of human papillomavirus and prostate carcinoma SO CANCER LA English DT Article DE human papillomavirus; prostate carcinoma; benign prostate hypertrophy; polymerase chain reaction; serology ID POLYMERASE CHAIN-REACTION; RISK-FACTORS; CERVICAL-CANCER; UNITED-STATES; HPV DNA; INFECTION; TYPE-16; TISSUE; VIRUS; PCR AB BACKGROUND. The presence of human papillomavirus (HPV) in the prostate and its role in prostate carcinoma are in dispute. To address these issues, two laboratories with extensive HPV experience were selected to test specimens from two populations at different risk for prostate carcinoma, using three different polymerase chain reaction (PCR) assays and two serologic assays for HPV. METHODS, The cases were comprised of 51 African-American (men at high risk far prostate carcinoma) and 15 Italian (men at intermediate risk for prostate carcinoma) men with prostate carcinoma. Controls were 108 African-American men and 40 Italian men with histologically proven benign prostate hypertrophy (BPH). Prostate tissue was obtained from each patient at surgery and immediately frozen in Liquid nitrogen. The PCR primer sets included two (MY09/MY11 and GP5+/GP6+) that amplify different regions of L1 and a third (WD66,67,154/WD72,76) targeted to E6. Sensitivity in the 2 L1 PCR assays was shown to be I HPV DNA genome per 100 cells. Serum antibodies to HPV-16 and HPV-11 virus-like particles (VLPs) were detected using enzyme-linked immunosorbent assays. RESULTS. All available prostate carcinoma tissue specimens (n = 63) and BPH specimens from selected controls (n = 61) were tested by PCR. Human beta-globin DNA could be amplified from all specimens except three carcinomas, but no HPV DNA was detected in any case or control specimens by MY09/MY11 or E6 PCR. Microdissection of 27 carcinoma specimens was conducted to minimize nontumor DNA, but results remained negative by MY09/MY11 and GP5+/GP6+ PCR. In addition, serum specimens in cases (n = 63) and controls (n = 144) showed no differences in their responses against HPV-16 (P = 0.54) or HPV-11 VLPs (P = 0.64). CONCLUSIONS. The findings suggest that HPV is not associated with prostate carcinoma, and that HPV DNA is not at all common in the prostate glands of older men. (C) 1998 American Cancer Society. C1 NCI, Viral Epidemiol Branch, NIH, Rockville, MD 20852 USA. Albert Einstein Coll Med, Canc Res Ctr, New York, NY USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. Howard Univ, Dept Urol, Washington, DC 20059 USA. St Orsola Marcello Malpighi Hosp, Dept Urol, Bologna, Italy. US FDA, Bethesda, MD 20014 USA. RP Strickler, HD (reprint author), NCI, Viral Epidemiol Branch, NIH, 6130 Execut Blvd,EPN Rm 434, Rockville, MD 20852 USA. NR 51 TC 51 Z9 53 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD MAR 15 PY 1998 VL 82 IS 6 BP 1118 EP 1125 PG 8 WC Oncology SC Oncology GA ZA556 UT WOS:000072376400016 PM 9506358 ER PT J AU Buchholz, TA Walden, TL Prestidge, BR AF Buchholz, TA Walden, TL Prestidge, BR TI Cost-effectiveness of posttreatment surveillance after radiation therapy for early stage seminoma SO CANCER LA English DT Article DE seminoma; radiation; cost; surveillance; patterns of failure ID II TESTICULAR SEMINOMA; TESTIS; RADIOTHERAPY; IRRADIATION; PATTERNS; EXPERIENCE; METASTASES; FAILURE; TUMORS AB BACKGROUND. This study evaluated the cost-effectiveness of posttreatment surveillance after radiation therapy for early stage seminoma. METHODS. From 1988-1995, 47 patients with Stage I, and 11 patients with Stage II seminoma (based on the Royal Marsden staging system) received paraaortic and pelvic lymph node radiation after radical orchiectomy. Patient records were reviewed and patients surveyed to determine the tests ordered for posttreatment surveillance. RESULTS. With a median follow-up of 55 months, there were 2 recurrences among the 58 patients. Eight-year actuarial disease free survival was 93%, with 100% overall survival. Information concerning follow-up screening was available for 56 patients. The follow-up tests ordered Included 842 physical examinations, 815 chest X-rays, 839 serum markers, 250 computerized tomography scans, and 112 abdominal plain films. The total cost of these examinations according to 1996 private sector charges and 1996 Medicare reimbursement rates, respectively, was $602,673.01 (average $10,762.02 per patient) and $282,746.52 (average $5049.05 per patient). The two patients who experienced recurrence were diagnosed independently of their posttreatment screening program. One patient recurred 7.5 months after his original diagnosis with an isolated spinal cord compression. The second patient had a mediastinum recurrence > 6 years after treatment. At last follow-up, both patients were disease free after salvage treatment. CONCLUSIONS, Patients with early stage seminoma treated with orchiectomy and radiation have excellent disease free survival rates. The cost of the surveillance program studied does not appear to be justifiable. (C) 1998 American Cancer Society. C1 Univ Texas, Md Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. Natl Canc Inst, Radiat Oncol Branch, Bethesda, MD USA. Wilford Hall USAF Med Ctr, Div Radiat Oncol, Lackland AFB, TX 78236 USA. RP Buchholz, TA (reprint author), Univ Texas, Md Anderson Canc Ctr, Dept Radiat Oncol, Box 97,1515 Holcombe Blvd, Houston, TX 77030 USA. NR 18 TC 16 Z9 16 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD MAR 15 PY 1998 VL 82 IS 6 BP 1126 EP 1133 DI 10.1002/(SICI)1097-0142(19980315)82:6<1126::AID-CNCR17>3.0.CO;2-8 PG 8 WC Oncology SC Oncology GA ZA556 UT WOS:000072376400017 PM 9506359 ER PT J AU Wingo, PA Ries, LAG Rosenberg, HM Miller, DS Edwards, BK AF Wingo, PA Ries, LAG Rosenberg, HM Miller, DS Edwards, BK TI Cancer incidence and mortality, 1973-1995 - A report card for the US SO CANCER LA English DT Article DE neoplasms; incidence; mortality; race; gender; Surveillance, Epidemiology and End Results program ID FATAL COLON-CANCER; UNITED-STATES; TRENDS; BREAST; RISK AB BACKGROUND. The American Cancer Society, the National Cancer Institute (NCI), and the Centers for Disease Control and Prevention including the National Center for Health Statistics (NCHS) agreed to produce together an annual "Report Card" to the nation on progress related to cancer prevention and control in the U.S. METHODS. This report provides average annual percent changes in incidence and mortality during 1973-1990 and 1590-1995, plus age-adjusted cancer incidence and death rates for whites, blacks, Asians and Pacific Islanders, and Hispanics. Information on newly diagnosed cancer cases is based on data collected by NCI, and information on cancer deaths is based on underlying causes of death as reported to NCHS. RESULTS. For all sites combined, cancer incidence rates decreased on average 0.7% per year during 1990-1995 (P > 0.05), in contrast to an increasing trend in earlier years. Among the ten leading cancer incidence sites, a similar reversal in trends was apparent for the cancers of the lung, prostate, colon/rectum, urinary bladder, and leukemia; female breast cancer incidence rates increased significantly during 1973-1990 but were level during 1990-1995. Cancer death rates for all sites combined decreased on average 0.5% per year during 1990-1995 (P < 0.05) after significantly increasing 0.4% per year during 1973-1990. Death rates for the four major cancers (lung, female breast, prostate, and colon/rectum) decreased significantly during 1990-1995. CONCLUSIONS. These apparent successes are encouraging and signal the need to maximize cancer control efforts in the future so that even greater in-roads in reducing the cancer burder, in the population are achieved. (C) 1998 American Cancel Society. C1 Amer Canc Soc, Epidemiol & Surveillance Res Dept, Atlanta, GA 30329 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Vital Stat, Hyattsville, MD 20782 USA. Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Canc Prevent & Control, Atlanta, GA USA. RP Wingo, PA (reprint author), Amer Canc Soc, Epidemiol & Surveillance Res Dept, 1599 Clifton Rd NE, Atlanta, GA 30329 USA. NR 28 TC 302 Z9 310 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 15 PY 1998 VL 82 IS 6 BP 1197 EP 1207 DI 10.1002/(SICI)1097-0142(19980315)82:6<1197::AID-CNCR26>3.0.CO;2-0 PG 11 WC Oncology SC Oncology GA ZA556 UT WOS:000072376400026 PM 9506368 ER PT J AU Shah, ZH Migliosi, V Miller, SCM Wang, AH Friedman, TB Jacobs, HT AF Shah, ZH Migliosi, V Miller, SCM Wang, AH Friedman, TB Jacobs, HT TI Chromosomal locations of three human nuclear genes (RPSM12, TUFM, and AFG3L1) specifying putative components of the mitochondrial gene expression apparatus SO GENOMICS LA English DT Article ID NON-SYNDROMIC DEAFNESS; DROSOPHILA-MELANOGASTER; CRITICAL REGION; MUTATION; PROTEIN; MAPS AB We have mapped the chromosomal locations of three human nuclear genes for putative components of the apparatus of mitochondrial gene expression, using a combination of in situ hybridization and interspecies hybrid mapping, The genes RPMS12 (mitoribosomal protein S12, a conserved protein component of the mitoribosomal accuracy center), TUFM (mitochondrial elongation factor EF-Tu), and AFG3L1 (similar to the yeast genes Afg3 and Real involved in the turnover of mistranslated or misfolded mtDNA-encoded polypeptides) were initially characterized by a combination of database sequence analysis, PCR, cloning, and DNA sequencing. RPMS12 maps to chromosome 19q13.1, close to the previously mapped gene for autosomal dominant hearing loss DFNA4. The TUFM gene is located on chromosome 16p11.2, with a putative pseudogene or variant (TUFML) located very close to the centromere of chromosome 17. AFG3L1 is located on chromosome 16q24, very close Do the telomere, By virtue of their inferred functions in mitochondria, these genes should be regarded as candidates of disorders sharing features with mitochondrial disease syndromes, such as sensorineural deafness, diabetes, and retinopathy. (C) 1998 Academic Press. C1 Univ Tampere, Inst Med Technol, FIN-33101 Tampere, Finland. Univ Glasgow, Inst Biomed & Life Sci, Glasgow G12 8QQ, Lanark, Scotland. Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, Rockville, MD 20850 USA. RP Jacobs, HT (reprint author), Univ Tampere, Inst Med Technol, POB 607, FIN-33101 Tampere, Finland. RI Shah, Zahid /G-9410-2014; Jacobs, Howard/G-2434-2011 OI Shah, Zahid /0000-0001-7165-8780; FU NIDCD NIH HHS [Z02 DC00038-01] NR 22 TC 13 Z9 13 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD MAR 15 PY 1998 VL 48 IS 3 BP 384 EP 388 DI 10.1006/geno.1997.5166 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA ZF473 UT WOS:000072901000016 PM 9545647 ER PT J AU Xiao, RP Tomhave, ED Wang, DJ Ji, XW Boluyt, MO Cheng, HP Lakatta, EG Koch, WJ AF Xiao, RP Tomhave, ED Wang, DJ Ji, XW Boluyt, MO Cheng, HP Lakatta, EG Koch, WJ TI Age-associated reductions in cardiac beta(1)- and beta(2)-adrenergic responses without changes in inhibitory G proteins or receptor kinases SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE beta-adrenergic receptor subtype; beta-adrenergic receptor kinase; aging; cardiac myocytes; inhibitory G proteins ID HUMAN VENTRICULAR MYOCARDIUM; FAILING HUMAN HEART; ADRENERGIC-RECEPTORS; ADENYLATE-CYCLASE; BETA-2 ADRENOCEPTORS; RAT-HEART; DESENSITIZATION; MYOCYTES; CATECHOLAMINES; CONTRACTION AB While an age-associated diminution in myocardial contractile response to beta-adrenergic receptor (beta-AR) stimulation has been widely demonstrated to occur in the context of increased levels of plasma catecholamines, some critical mechanisms that govern beta-AR signaling must still be examined in aged hearts, Specifically, the contribution of beta-AR subtypes (beta(1) versus beta(2)) to the overall reduction in contractile response with aging is unknown, Additionally, whether G protein-coupled receptor kinases (GRKs), which mediate receptor desensitization, or adenylyl cyclase inhibitory G proteins (G(i)) are increased with aging has not been examined, Both these inhibitory mechanisms are upregulated in chronic heart failure, a condition also associated with diminished beta-AR responsiveness and increased circulatory catecholamines. In this study, the contractile responses to both beta(1)-AR and beta(2)-AR stimulation were examined in rat ventricular myocytes of a broad age range (2, 8, and 24 mo), A marked age-associated depression in contractile response to both beta-AR subtype stimulation was observed, This was associated with a nonselective reduction in the density of both beta-AR subtypes and a reduction in membrane adenylyl cyclase response to both beta-AR subtype agonists, NaF or forskolin, However, the age-associated diminutions in contractile responses to either beta(1)-AR or beta(2)-AR stimulation were not rescued by inhibiting G(i) with pertussis toxin treatment, Further, the abundance or activity of beta-adrenergic receptor kinase, GRK5, or G(i) did not significantly change with aging. Thus, we conclude that the positive inotropic effects of both beta(1)- and beta(2)-AR stimulation are markedly decreased with aging in rat ventricular myocytes and this is accompanied by decreases in both beta-AR subtype densities and a reduction in membrane adenylate cyclase activity, Neither GRKs nor G(i) proteins appear to contribute to the age-associated reduction in cardiac beta-AR responsiveness. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. RP Xiao, RP (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, 4940 Eastern Ave, Baltimore, MD 21224 USA. EM XiaoR@GRC.NIA.NIH.Gov NR 46 TC 121 Z9 124 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR 15 PY 1998 VL 101 IS 6 BP 1273 EP 1282 DI 10.1172/JCI1335 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZE072 UT WOS:000072754900010 PM 9502768 ER PT J AU Long, XL Crow, MT Sollott, SJ O'Neill, L Menees, DS Hipolito, MD Boluyt, MO Asai, T Lakatta, EG AF Long, XL Crow, MT Sollott, SJ O'Neill, L Menees, DS Hipolito, MD Boluyt, MO Asai, T Lakatta, EG TI Enhanced expression of p53 and apoptosis induced by blockade of the vacuolar proton ATPase in cardiomyocytes SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE p53; cardiac myocyte; apoptosis; bafilomycin A1; vacuolar proton ATPase ID COLONY-STIMULATING FACTOR; CELL-DEATH; INTRACELLULAR ACIDIFICATION; RABBIT CARDIOMYOCYTES; CARDIAC MYOCYTES; MESSENGER-RNA; HL-60 CELLS; RAT; ENDONUCLEASE; PH AB Activation of the vacuolar proton ATPase (VPATPase) has been implicated in the prevention of apoptosis in neutrophils and adult cardiac myocytes. To determine the role of the VPATPase in apoptosis of cardiac myocytes, we used a potent and specific inhibitor of the VPATPase, bafilomycin A1. Bafilomycin A1 alone caused increased DNA laddering of genomic DNA and increased nuclear staining for fragmented DNA in neonatal cardiomyocyte apoptosis in a dose- and time-dependent manner. Intracellular acidification in cardiac myocytes was also observed after 18 h of bafilomycin A1 treatment, Accordingly, bafilomycin A1-treated myocytes also showed increased accumulation of p53 protein and p53-dependent transactivation of gene expression, including a persistent upregulation of p21/wild-type p53 activated fragment 1/cyclin kinase inhibitor protein-1 mRNA. The bafilomycin A1-induced increase in p53 protein levels was accompanied by a marked increase in p53 mRNA accumulation. In contrast, cardiac fibroblasts treated with bafilomycin A1 showed no change in p53 protein expression or pH(i) and did not undergo apoptosis even after 24 h of treatment. Our data suggest that blockade of the VPATPase induces apoptotic cell death of cardiac myocytes and that this may occur through a p53-mediated apoptotic pathway. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 4940 Eastern Ave, Baltimore, MD 21224 USA. EM LakattaE@grc.nia.nih.gov NR 41 TC 58 Z9 62 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR 15 PY 1998 VL 101 IS 6 BP 1453 EP 1461 DI 10.1172/JCI345 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZE072 UT WOS:000072754900030 PM 9502788 ER PT J AU Scharton-Kersten, T Nakajima, H Yap, G Sher, A Leonard, WJ AF Scharton-Kersten, T Nakajima, H Yap, G Sher, A Leonard, WJ TI Cutting edge: Infection of mice lacking the common cytokine receptor gamma-chain (gamma(c)) reveals an unexpected role for CD4(+) T lymphocytes in early IFN-gamma-dependent resistance to Toxoplasma gondii SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; LYMPHOID DEVELOPMENT; INTERFERON-GAMMA; INTERLEUKIN-12; EXPRESSION; PARASITE; ANTIBODY; ABSENCE; CELLS AB Mice lacking the common cytokine receptor gamma-chain (gamma(c)) gene exhibit defective development of NK cells and CD8(+) T cells and greatly diminished production of IFN-gamma, Because resistance of SCID mice to Toxoplasma gondii requires IL-12-dependent IFN-gamma production by NK cells, we expected that gamma(c)-deficient mice would succumb rapidly to the parasite, Surprisingly, however, most gamma(c)-deficient mice survived the acute phase of T. gondii infection. As in wild-type mice, this resistance required IL-12 and IFN-gamma; nevertheless, whereas wild-type mice depleted of CD4(+) T cells survived, anti-CD4(+) treated gamma(c)-deficient mice displayed diminished production of IFN-gamma and all succumbed to acute infection. These data not only reveal a role for CD4(+) T lymphocytes in IFN-gamma-dependent host defense but also establish SCID and gamma(c)-deficient mice as powerful complementary tools for assessing the function of NK vs CD4(+) T cells in immunopathophysiologic responses. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Rm 7N252, Bethesda, MD 20892 USA. EM alan_sher@nih.gov; wjl@helix.nih.gov NR 22 TC 30 Z9 32 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 1998 VL 160 IS 6 BP 2565 EP 2569 PG 5 WC Immunology SC Immunology GA ZA798 UT WOS:000072402900003 PM 9510152 ER PT J AU Murakami, M Paul, WE AF Murakami, M Paul, WE TI Age-dependent appearance of NK1.1(+) T cells in the livers of beta(2)-microglobulin knockout and SJL mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROMPTLY PRODUCE INTERLEUKIN-4; RECEPTOR-ALPHA-CHAIN; CLASS-I MOLECULES; CD8 THYMOCYTES; FAMILY; SUBSET; CD4(+); CD4+; LYMPHOCYTES; EXPRESSION AB NK1.1(+) T cells, a specialized set of T cells that recognize CD1, are reportedly absent in young beta(2)-microglobulin-deficient (beta(2)m-knockout (KO)) and SJL mice, In this study, we show that a significant number of NK1.1(+) T cells exist in the livers of older beta(2)m-KO and SJL mice, and that the number of liver NK1.1(+) T cells increases as the animals age. The surface phenotypes of liver NK1.1(+) T cells from beta(2)m-KO and SJL mice were similar to NK1.1(+) T cells from C57BL/6 mice, except that the bulk of these cells were CD4(-)CD8(-). After anti-CD3 injection in vivo, the cells promptly expressed IL-4 mRNA just as NK1.1(+) T cells did in normal mice. Using L cells expressing CD1, liver NK1.1(+) T cells from both beta(2)m-KO and SJL mice were stimulated to proliferate, although to a lesser degree than were such cells from C57BL/6 mice. Our studies show that some NK1.1(+) T cells accumulate in the livers of older beta(2)m-KO and SJL mice, and that they appear to have functional properties similar to "normal" NK1.1(+) T cells. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Paul, WE (reprint author), NIAID, Immunol Lab, NIH, 10 Ctr Dr MSC 1892,Bldg 10,Rm 11N311, Bethesda, MD 20892 USA. NR 31 TC 17 Z9 18 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 1998 VL 160 IS 6 BP 2649 EP 2654 PG 6 WC Immunology SC Immunology GA ZA798 UT WOS:000072402900014 PM 9510163 ER PT J AU Rellahan, BL Jensen, JP Howcroft, TK Singer, DS Bonvini, E Weissman, AM AF Rellahan, BL Jensen, JP Howcroft, TK Singer, DS Bonvini, E Weissman, AM TI Elf-1 regulates basal expression from the T cell antigen receptor zeta-chain gene promoter SO JOURNAL OF IMMUNOLOGY LA English DT Article ID AP-1 TRANSCRIPTION FACTORS; DNA-BINDING SPECIFICITIES; FAMILY PROTEINS; POTENTIAL ROLE; ALPHA-GENE; ETS; ACTIVATION; ENHANCER; ELEMENTS; SITES AB In mature T cells, limited synthesis of the TCR-zeta subunit is primarily responsible for regulating surface expression of TCRs, Transcription of zeta is directed by a complex promoter that includes two potential binding sites for the Ets family of transcription factors at -52 (2EBS1) and -135 (zEBS2), Mutation of these two sites results in a marked reduction of transcription from this promoter, Using electrophoretic mobility shift analysis, Elf-1 was demonstrated to be the Ets family member that binds to these sites, One site, zEBS1, matches the optimal Elf-1 consensus sequence in eight of nine bases? making it the best match of any known mammalian Elf-1 binding site, A role for Elf-1 in TCR-zeta trans-activation was confirmed by ectopic expression of Elf-1 in COS-7 cells, This resulted in an increase in TCR-zeta promoter activity that mapped to 2EBS1 and zEBS2, Additional support for the involvement of Elf-1 in TCR-zeta trans-activation derives from the finding that a GAL4-Elf-1 fusion protein trans-activated TCR-zeta promoter constructs that had been modified to contain GAL4 DNA binding sites, These results demonstrate that Elf-1 plays an essential role in the trans-activation of a constitutively expressed T cell-specific gene, and that trans-activation occurs in the context of the native promoter in both lymphoid and nonlymphoid cells. Taken together with the existing literature, these data also suggest that the requirement for inducible factors in Elf-1-mediated trans-activation may decrease as the affinity and number of Elf-1 sites increase. C1 US FDA, Ctr Biol Evaluat & Res, Immunobiol Lab, Rockville, MD 20892 USA. NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Rellahan, BL (reprint author), US FDA, Ctr Biol Evaluat & Res, Immunobiol Lab, Bldg 29B,Room 5E16,HFM 564,1401 Rockville Pike, Rockville, MD 20892 USA. EM rellahan@al.cber.fda.gov NR 44 TC 35 Z9 37 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 1998 VL 160 IS 6 BP 2794 EP 2801 PG 8 WC Immunology SC Immunology GA ZA798 UT WOS:000072402900032 PM 9510181 ER PT J AU Jelonek, MT Classon, BJ Hudson, PJ Margulies, DH AF Jelonek, MT Classon, BJ Hudson, PJ Margulies, DH TI Direct binding of the MHC class I molecule H-2L(d) to CD8: Interaction with the amino terminus of a mature cell surface protein SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CYTOTOXIC T-LYMPHOCYTES; INSULIN-RECEPTORS; ALPHA-3 DOMAIN; 3-DIMENSIONAL STRUCTURE; ANTIGENIC PEPTIDES; PLASMON RESONANCE; CRYSTAL-STRUCTURE; CROSS-LINKING; SOLUBLE FORM AB MHC class I molecules (MHC-I) display peptides from the intracellular pool at the cell surface for recognition by T lymphocytes bearing alpha beta TCR, Although the activation of T cells is controlled by the interaction of the TCR with MHC/peptide complexes, the degree and extent of the activation is influenced by the binding in parallel of the CD8 coreceptor with MHC-I. In the course of quantitative evaluation of the binding of purified MHC-I to engineered CD8, we observed that peptide-deficient H-2L(d) (MHC-I) molecules bound with moderate affinity (K-d = 7.96 x 10(-7) M), but in the presence of H-2L(d)-binding peptides, no interaction was observed. Examination of the amino terminal sequences of CD8 alpha and beta chains suggested that H-2L(d) might bind these protein termini via its peptide binding cleft, Using both competition and real-time direct assays based on surface plasmon resonance, we detected binding of empty H-2L(d) to synthetic peptides representing these termini, These results suggest that some MHC molecules are capable of binding the amino termini of intact cell surface proteins through their binding groove and provide alternative explanations for the observed binding of MHC molecules to a variety of cell surface receptors and coreceptors. C1 NIAID, Mol Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. Walter & Eliza Hall Inst Med Res, Parkville, Vic, Australia. RP Margulies, DH (reprint author), NIAID, Mol Biol Sect, Immunol Lab, NIH, Bldg 10,Room 11N311, Bethesda, MD 20892 USA. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 67 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 1998 VL 160 IS 6 BP 2809 EP 2814 PG 6 WC Immunology SC Immunology GA ZA798 UT WOS:000072402900034 PM 9510183 ER PT J AU Ameratunga, R Winkelstein, JA Brody, L Binns, M Cork, LC Colombani, P Valle, D AF Ameratunga, R Winkelstein, JA Brody, L Binns, M Cork, LC Colombani, P Valle, D TI Molecular analysis of the third component of canine complement (C3) and identification of the mutation responsible for hereditary canine C3 deficiency SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GENETICALLY-DETERMINED DEFICIENCY; 3RD COMPONENT; INHERITED DEFICIENCY; GUINEA-PIGS; DOGS; C-3; SEQUENCE; IMMUNITY; PATIENT; BINDING AB Genetically determined deficiency of the third component of complement (C3) in the dog is characterized by a predisposition to recurrent bacterial infections and to type 1 membranoproliferative glomerulonephritis. The current studies were undertaken to characterize the cDNA for wild-type canine C3 and identify the molecular basis for hereditary canine C3 deficiency, Amplification, cloning, and sequence analysis indicated that canine C3 is highly conserved in comparison with human, mouse, and guinea pig C3. Southern blot analysis failed to show any gross deletions or rearrangements of DNA from C3-deficient animals, Northern blot analysis indicated that the livers of these animals contain markedly reduced quantities of a normal length C3 mRNA, The full-length 5.1-kb canine C3 cDNA mas amplified in overlapping PCR fragments, Sequence analysis of these fragments has shown a deletion of a cytosine at position 2136 (codon 712), leading to a frameshift that generates a stop codon 11 amino acids downstream, The deletion has been confirmed in genomic DNA, and its inheritance has been demonstrated by allele-specific oligonucleotide hybridization. C1 Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21287 USA. NIH, Human Genome Res Inst, Bethesda, MD 20892 USA. Stanford Univ, Dept Comparat Med, Stanford, CA 94305 USA. Anim Hlth Trust, Newmarket, Suffolk, England. RP Winkelstein, JA (reprint author), Johns Hopkins Hosp, CMSC 1103,600 N Wolfe St, Baltimore, MD 21287 USA. FU NIAID NIH HHS [AI-19278] NR 31 TC 23 Z9 24 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 1998 VL 160 IS 6 BP 2824 EP 2830 PG 7 WC Immunology SC Immunology GA ZA798 UT WOS:000072402900036 PM 9510185 ER PT J AU Perry, LL Feilzer, K Portis, JL Caldwell, HD AF Perry, LL Feilzer, K Portis, JL Caldwell, HD TI Distinct homing pathways direct T lymphocytes to the genital and intestinal mucosae in Chlamydia-infected mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL-ADHESION MOLECULE-1; OUTER-MEMBRANE PROTEIN; VACCINE DEVELOPMENT; TRACHOMATIS; MEMORY; INTEGRINS; SYSTEM; HYPERSENSITIVITY; DIFFERENTIATION; INFLAMMATION AB Immunity to genital tract infection with Chlamydia trachomatis is mediated by type 1 CD4(+) T lymphocytes, To define the signals that govern lymphocyte trafficking to the genital mucosa, integrins expressed by infiltrating T cells and endothelial addressins displayed on local vasculature were characterized during the course of infection, All T cells expressed the alpha(L) beta(2) heterodimer that binds vascular ICAM-1, and most displayed enhanced levels of the alpha(4) beta(1) integrin that interacts with VCAM-1, alpha(E) and beta(7)(low) integrin chains were detected on approximately 15 and 30% of infiltrating T cells, respectively, Lymphocytes derived from the spleen or draining lymph nodes expressed this same integrin profile, suggesting that cells are recruited to the genital mucosa from the systemic circulation without significant selection pressure for these markers, Immunofluorescent staining for the corresponding vascular addressins revealed intense expression of VCAM-1 on small vessels within Chlamydia-infected genital tracts and up-regulation of ICAM-1 on endothelial, stromal, and epithelial cells, Mucosal addressin cell adhesion molecule-1 was not detected within genital tissues, These results indicate that T lymphocyte homing to the genital mucosa requires the interaction of alpha(L) beta(2) and alpha(4) beta(1) with endothelial ICAM-1 and VCAM-1, respectively, which is the same pathway that directs lymphocytes to systemic sites of inflammation, Homing pathways defined for the intestinal mucosa and assumed to be relevant to all mucosal sites are not well represented in the genital tract, The identification of T lymphocyte trafficking pathways shared between systemic and mucosal tissues should facilitate vaccine strategies aimed at maximizing immune responses against Chlamydia and other pathogens of the urogenital tract. C1 NIAID, Rocky Mt Labs, Intracellular Parasites Lab, NIH, Hamilton, MT 59840 USA. RP Perry, LL (reprint author), NIAID, Rocky Mt Labs, Intracellular Parasites Lab, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 42 TC 60 Z9 61 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 1998 VL 160 IS 6 BP 2905 EP 2914 PG 10 WC Immunology SC Immunology GA ZA798 UT WOS:000072402900045 PM 9510194 ER PT J AU Jurewicz, A Biddison, WE Antel, JP AF Jurewicz, A Biddison, WE Antel, JP TI MHC class I-restricted lysis of human oligodendrocytes by myelin basic protein peptide-specific CD8 T lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; CELL SUBSETS; COMPLEX; SUSCEPTIBILITY; DEMYELINATION; ASTROCYTES; EXPRESSION; LESIONS AB Multiple sclerosis (MS) is considered to be an autoimmune disease that is directed either at myelin or at its cell of origin, the oligodendrocytes (OL). The inflammatory lesions in the central nervous system contain multiple myelin Ag-restricted and nonrestricted cell populations with the potential to mediate tissue injury. Previous studies indicate that it is possible to generate MHC class I-restricted myelin peptide-specific cytotoxic CD8 T cells, and that human adult OLs express MHC class I molecules in vitro, The purpose of this study was to demonstrate that myelin basic protein peptide-specific CD8 T cells could induce OL injury, We generated CD8 T cell lines from six healthy donors and five MS patients, and all cell lines were HLA-A2 positive, The obtained CD8 cell lines induced lysis of HLA-A2- but not HLA-A3-transfected HMy2.C1R cells in the presence of myelin basic protein peptide 110-118. In the absence of exogenous peptide, the CD8 T cell lines Here cytotoxic to HLA-A2 but not to non-HLA-A2 OLs, Cytotoxicity was blocked with anti-MHC class I-blocking Ab. These results support the postulate that autoreactive CD8 cytotoxic T cells can contribute to the tissue injury in MS. C1 McGill Univ, Montreal Neurol Inst, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada. NIH, Neuroimmunol Branch, Bethesda, MD 20892 USA. RP Antel, JP (reprint author), Montreal Neurol Hosp & Inst, Dept Neurol, 3801 Univ St, Montreal, PQ H3A 2B4, Canada. NR 28 TC 114 Z9 116 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 1998 VL 160 IS 6 BP 3056 EP 3059 PG 4 WC Immunology SC Immunology GA ZA798 UT WOS:000072402900062 PM 9510211 ER PT J AU Chauthaiwale, JV Lockwich, TP Ambudkar, IS AF Chauthaiwale, JV Lockwich, TP Ambudkar, IS TI Characteristics of a low affinity passive Ca2+ influx component in rat parotid gland basolateral plasma membrane vesicles SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE Ca2+ influx; parotid gland; BLMV; kinetics; divalent cations ID DIVALENT-CATION ENTRY; ACINAR-CELLS; MAST-CELLS; CALCIUM CURRENT; STIMULATION; ACTIVATION; PERMEABILITY; MECHANISMS; PATHWAYS; CA-2+ AB We have previously reported the presence of two Ca2+ influx components with relatively high (K-Ca = 152 +/- 79 mu M) and low (K-Ca = 2.4 +/- 0.9 mM) affinities for Ca2+ in internal Ca2+ pool-depleted rat parotid acinar cells [Chauthaiwale et al. (1996) Pfluegers Arch. 432:105-111]. We have also reported the presence of a high affinity Ca2+ influx component with K-Ca = 279 +/- 43 mu M in rat parotid gland basolateral plasma membrane vesicles (BLMV). [Lockwich, Kim & Ambudkar (1994) J. Membrane Biol. 141:289-296]. The present studies show that a low affinity Ca2+ influx component is also present in BLMV with K-Ca = 2.3 +/- 0.41 mM (V-max = 16.36 +/- 4.11 nmoles of Ca2+/mg protein/min). Our data demonstrate that this low affinity component is similar to the low affinity Ca2+ influx component that is activated by internal Ca2+ store depletion in dispersed parotid gland acini by the following criteria: (i) similar K-Ca, for calcium flux, (ii) similar IC50 for inhibition by Ni2+ and Zn2+; (iii) increase in K-Ca at high external K+, (iv) similar effects of external pH. The high affinity Ca2+ influx in cells is different from the low affinity Ca2+ influx component cells in its sensitivity to pH, KCl, Zn2+ and Ni2+. The low and high affinity Ca2+ influx components in BLMV can also be distinguished from each other based on the effects of Zn2+, Ni2+, KCl, and dicyclohexylcarbodiimide. In aggregate, these data demonstrate the presence of a low affinity passive Ca2+ influx pathway in BLMV which displays characteristics similar to the low affinity Ca2+ influx component detected in parotid acinar cells following internal Ca2+ store depletion. C1 NIDR, NIH, Secretory Physiol Sect, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. RP Ambudkar, IS (reprint author), NIDR, NIH, Secretory Physiol Sect, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. NR 24 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD MAR 15 PY 1998 VL 162 IS 2 BP 139 EP 145 DI 10.1007/s002329900351 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA ZC175 UT WOS:000072548300006 PM 9538507 ER PT J AU Sharp, CW AF Sharp, CW TI Perspectives of neuroimmune issues and substances of abuse SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Editorial Material C1 NIDA, Special Programs, Rockville, MD 20857 USA. RP Sharp, CW (reprint author), NIDA, Special Programs, Room 10A-31,5600 Fishers Lane, Rockville, MD 20857 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD MAR 15 PY 1998 VL 83 IS 1-2 BP 1 EP 3 PG 3 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA ZP561 UT WOS:000073765800001 PM 9610667 ER PT J AU Wu, VW Schwartz, JP AF Wu, VW Schwartz, JP TI Cell culture models for reactive gliosis: New perspectives SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Review DE astrocytes; microglia; neurons; cytokine; brain injury ID FIBRILLARY ACIDIC PROTEIN; CENTRAL-NERVOUS-SYSTEM; ADULT-RAT-BRAIN; NEUROTROPHIC FACTOR; PARKINSONS-DISEASE; GENE-EXPRESSION; INDUCED-INJURY; GROWTH-FACTOR; KAINIC ACID; ASTROCYTES AB Reactive gliosis, which occurs in response to any damage or disturbance to the central nervous system, has been recognized for many years, but is still not completely understood, The hallmark is the increased expression of glial fibrillary acidic protein (GFAP), yet studies in GFAP knockout mice suggest that GFAP may not be required for an astrocyte to become hypertrophic. In this review, we describe a series of tissue culture models that have been established in order to address: 1) the biochemical phenotype of reactive astrocytes; 2) the factor and/or cell responsible for induction of gliosis; 3) the mechanisms by which one might block the induction, These models range from cultures of astrocytes, both neonatal and adult, to co-cultures of astrocytes with either neurons or microglia, to organ cultures, None is ideal: each addresses a different set of questions, but taken together, they are beginning to provide useful information which should allow a better understanding of the plasticity response of astrocytes to brain injury. (C) 1998 Wiley-Liss, Inc. C1 NINDS, MGS, CNB, NIH, Bethesda, MD 20892 USA. RP Schwartz, JP (reprint author), NINDS, MGS, CNB, NIH, Bldg 10,Room 3N256, Bethesda, MD 20892 USA. NR 48 TC 102 Z9 102 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD MAR 15 PY 1998 VL 51 IS 6 BP 675 EP 681 DI 10.1002/(SICI)1097-4547(19980315)51:6<675::AID-JNR2>3.0.CO;2-8 PG 7 WC Neurosciences SC Neurosciences & Neurology GA ZD129 UT WOS:000072654300002 PM 9545082 ER PT J AU Bicout, D Magyar, P Riess, J AF Bicout, D Magyar, P Riess, J TI Conductivities of a quantum Hall system with a model disorder potential: Influence of electron-phonon interaction on plateau widths SO PHYSICAL REVIEW B LA English DT Article ID STRONG MAGNETIC-FIELDS; GAAS/ALXGA1-XAS HETEROSTRUCTURES; TIME EVOLUTION; SCATTERING; REGIME; CONDUCTANCE; DYNAMICS; LOCALIZATION; BREAKDOWN; MOBILITY AB We consider noninteracting electrons in a quasi-two-dimensional strip (extended in the x direction) in the presence of a strong perpendicular magnetic field and a constant electric field in the y direction, and subject to a model disorder potential V(x,y) ("toy model") which allows us to obtain the exact solutions of the time-dependent Schrodinger equation in very good approximation. Further, the electrons are coupled to a heat bath (accoustic phonons) at temperature T that modifies the coherent Schrodinger time evolution induced by the electric field E-y. After elimination of macroscopically unobservable fluctuations by averaging over suitable short time intervals, the time evolution that is relevant for the macroscopic current density can be described by a Boltzmann-type equation, which is solved numerically. The steady-state solution allows us to calculate sigma(yy) and sigma(xy) as a function of any physical parameter of the system. Here we give results of sigma(yy) and of sigma(xy) for all filling factors and as a function of temperature. Quantized Hall plateaus are obtained at the correct values with high precision. Between two plateaus, the Shubnikov-de Haas peak spreads out and its maximum decreases with increasing temperature in qualitative accordance with typical quantum Hall samples. Further, we obtain the remarkable result that for temperatures below 5 K the plateaus of sigma(xy) become sensibly larger than those of sigma(yy). Our analysis shows that this effect results from electron-phonon interaction. (Such a phenomenon has been known experimentally for a long time, but it has seemed unexplained so far.) Our method of calculation could, in principle, be extended to more complex disorder potentials. C1 NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Grenoble 1, Ctr Rech Tres Basses Temp, CNRS, F-38042 Grenoble 9, France. RP Bicout, D (reprint author), NIDDK, Phys Chem Lab, NIH, Bldg 5,Room 136, Bethesda, MD 20892 USA. NR 36 TC 9 Z9 9 U1 0 U2 0 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1098-0121 EI 1550-235X J9 PHYS REV B JI Phys. Rev. B PD MAR 15 PY 1998 VL 57 IS 12 BP 7228 EP 7239 DI 10.1103/PhysRevB.57.7228 PG 12 WC Physics, Condensed Matter SC Physics GA ZE126 UT WOS:000072760300071 ER PT J AU Ganz, PA Day, R Costantino, J AF Ganz, PA Day, R Costantino, J TI Compliance with quality of life data collection in the National Surgical Adjuvant Breast and Bowel Project (NSABP) Breast Cancer Prevention Trial SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT Workshop on Missing Data in Quality of Life Research in Cancer Clinical Trials - Practical and Methodological Issues CY JUL 01-03, 1997 CL BAD HORN, SWITZERLAND SP Swiss Group Clin Canc Res ID SERUM-LIPOPROTEINS; CLINICAL-TRIAL; PLASMA-LIPIDS; TAMOXIFEN AB This paper describes compliance with the completion of a quality of life questionnaire in the Breast Cancer Prevention Trial, a large multi-centre randomized trial that is studying the efficacy of Tamoxifen in preventing breast cancer. In the first 4875 women enrolled in the control arm of the study, there was a very high rate of questionnaire completion at baseline, 3 months, 6 months and 12 months of follow-up (89.8 per cent completed forms at 12 months). The sample was examined according to demographic and risk factors, as well as by recruitment cohort. There was a significantly poorer compliance rate for the most recently recruited cohort that was followed-up during a time of substantial external negative publicity related to clinical trial research. Nevertheless, the overall compliance with completion of quality of life data in this trial is very high, which is probably attributable to the high educational status of the trial participants. (C) 1998 John Wiley & Sons, Ltd. C1 Univ Calif Los Angeles, Div Canc Prevent & Control, Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Ctr Biostat, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. RP Ganz, PA (reprint author), Univ Calif Los Angeles, Div Canc Prevent & Control, Sch Med, 1100 Glendon Ave,Suite 711, Los Angeles, CA 90024 USA. EM pganz@med1.medsch.ucla.edu NR 14 TC 19 Z9 19 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAR 15 PY 1998 VL 17 IS 5-7 BP 613 EP 622 DI 10.1002/(SICI)1097-0258(19980315/15)17:5/7<613::AID-SIM808>3.0.CO;2-9 PG 10 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA ZB211 UT WOS:000072447800011 PM 9549810 ER PT J AU Lubin, JH Fraumeni, JF AF Lubin, JH Fraumeni, JF TI Effect on mortality of switching from cigarettes to pipes or cigars - American study supported conclusions SO BRITISH MEDICAL JOURNAL LA English DT Letter ID LUNG-CANCER RISK C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Lubin, JH (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD MAR 14 PY 1998 VL 316 IS 7134 BP 863 EP 863 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA ZC488 UT WOS:000072584300056 PM 9549474 ER PT J AU Daly, S Mills, J Molloy, A Kirke, P Scott, J AF Daly, S Mills, J Molloy, A Kirke, P Scott, J TI Folic acid food fortification to prevent neural tube defects - Reply SO LANCET LA English DT Letter C1 Thomas Jefferson Univ, Jefferson Med Coll, Dept Obstet & Gynecol, Philadelphia, PA 19107 USA. NICHD, NIH, Bethesda, MD USA. Trinity Coll, Dublin, Ireland. Hlth Res Board, Dublin, Ireland. RP Daly, S (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Obstet & Gynecol, Philadelphia, PA 19107 USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAR 14 PY 1998 VL 351 IS 9105 BP 834 EP 835 DI 10.1016/S0140-6736(05)78968-6 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA ZB916 UT WOS:000072521200060 ER PT J AU Leyton, J Coelho, T Coy, DH Jakowlew, S Birrer, MJ Moody, TW AF Leyton, J Coelho, T Coy, DH Jakowlew, S Birrer, MJ Moody, TW TI PACAP(6-38) inhibits the growth of prostate cancer cells SO CANCER LETTERS LA English DT Article DE PACAP; prostate cancer; proliferation; receptor antagonist; VIP ID VASOACTIVE-INTESTINAL-PEPTIDE; CYCLASE-ACTIVATING POLYPEPTIDE; RAT VENTRAL PROSTATE; ISOLATED EPITHELIAL-CELLS; STIMULATES C-FOS; ADENYLATE-CYCLASE; FUNCTIONAL EXPRESSION; SIGNAL-TRANSDUCTION; SPLICE VARIANTS; MESSENGER-RNAS AB The effects of pituitary adenylyl cyclase activating polypeptide (PACAP) analogs on prostate cancer cell lines was investigated. I-125-PACAP-27 bound with high affinity to PC-3 cells (K-d = 10 nM) to a single class of sites (B-max = 30000/cell). By RT-PCR, a major 305 bp band was observed using cDNA derived from PC-3, LNCaP or DU-145 cells. Specific I-125-PACAP binding was inhibited with high affinity by PACAP-27, PACAP-38 and PACAP(6-38) (IC50 values of 15, 10 and 300 nM, respectively) but not by PACAP(28-38). PACAP elevated cAMP and the increase caused by PACAP-27 was reversed by PACAP(6-38). PACAP transiently increased c-fos gene expression and the increase in c-fos mRNA was reversed by PACAP(6-38). PACAP-27 stimulated colony formation in PC-3 cells, whereas PACAP(6-38) reduced colony number and size. In nude mice bearing PC-3 xenografts, PACAP(6-38) significantly slowed tumor growth. These data suggest that biologically active type 1 PACAP receptors are present on human prostate cancer cells and that prostate cancer cell growth is inhibited by PACAP(6-38). (C) 1998 Elsevier Science Ireland Ltd. C1 NCI, Med Branch, Dept Cell & Canc Biol, Rockville, MD 20850 USA. Tulane Univ, Sch Med, Peptide Res Lab, Dept Med, New Orleans, LA 70112 USA. RP Leyton, J (reprint author), NCI, Med Branch, Dept Cell & Canc Biol, Bldg KWC,Room 300,9610 Med Ctr Dr, Rockville, MD 20850 USA. FU NIDDK NIH HHS [DK-36107] NR 33 TC 26 Z9 26 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD MAR 13 PY 1998 VL 125 IS 1-2 BP 131 EP 139 DI 10.1016/S0304-3835(97)00525-9 PG 9 WC Oncology SC Oncology GA ZE238 UT WOS:000072772000020 PM 9566707 ER PT J AU Avramoglu, RK Nimpf, J McLeod, RS Ko, KWS Wang, YW FitzGerald, D Yao, ZM AF Avramoglu, RK Nimpf, J McLeod, RS Ko, KWS Wang, YW FitzGerald, D Yao, ZM TI Functional expression of the chicken low density lipoprotein receptor-related protein in a mutant Chinese hamster ovary cell line restores toxicity of Pseudomonas exotoxin A and degradation of alpha(2)-macroglobulin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID B-CONTAINING LIPOPROTEINS; ALPHA-2-MACROGLOBULIN RECEPTOR; APOLIPOPROTEIN-E; INSULIN-RECEPTOR; MICE LACKING; BINDING; AERUGINOSA; SECRETION; LRP; CHYLOMICRONS AB The low density lipoprotein receptor-related protein (LRP) is responsible for the clearance of several physiological ligands including a complex of proteinase and alpha(2)-macroglobulin (alpha(2)M) and for the entrance of Pseudomonas exotoxin A (PEA) into cells, We have prepared expression plasmids for the full-length chicken LRP (designated LRP100) and two intermediates encoding 25 and 67% of the receptor (designated LRP25 and LRP67, respectively) using overlapping: cDNA fragments, LRP25 and LRP67 encode the N-terminal 22 and 64%, respectively, of LRP100 plus the transmembrane and intracellular domains, Transient transfection of these plasmids into COS-7 cells yielded recombinant proteins of expected molecular mass and immunoreactivity, However, LRP100 was incompletely processed into alpha- (515-kDa) and beta- (85-kDa) chains and was poorly transported from the endoplasmic reticulum to the Golgi compartment. Stable transformants of LRP100, LRP67, and LRP25 were generated in a mutant Chinese hamster ovary cell line that lacked expression of endogenous LRP and was resistant to PEA. All forms of recombinant LRP proteins were transported from the endoplasmic reticulum to the Golgi apparatus in Chinese hamster ovary cells as shown by their sensitivity to endoglycosidase H and resistance to neuraminidase. Cell surface iodination and subcellular fractionation studies indicated that all three LRP variants were expressed on the plasma membrane, Furthermore, expression of the three LRP variants restored, to various degrees, sensitivity to PEA and the ability to degrade methylamine-activated alpha(2)M (alpha(2)M*). These data suggest that deletion of large internal portions of LRP, including the processing site, does not prevent transport of LRP to the plasma membrane, nor does it abolish the interaction of LRP with alpha(2)M* or PEA. This LRP expression system may allow for the characterization of domains within LRP responsible for its multifunctionality. C1 Univ Ottawa, Inst Heart, Dept Pathol & Lab Med, Lipoprot & Atherosclerosis Grp, Ottawa, ON K1Y 4E9, Canada. Univ Ottawa, Inst Heart, Dept Biochem, Lipoprot & Atherosclerosis Grp, Ottawa, ON K1Y 4E9, Canada. Univ Vienna, Vienna, Austria. Bioctr, Dept Mol Genet, Vienna, Austria. NCI, Mol Biol Lab, Div Canc Biol Diag & Ctr, NIH, Bethesda, MD 20892 USA. RP Yao, ZM (reprint author), Univ Ottawa, Inst Heart, Dept Pathol & Lab Med, Lipoprot & Atherosclerosis Grp, Ottawa, ON K1Y 4E9, Canada. RI McLeod, Roger/F-8014-2015 OI McLeod, Roger/0000-0002-6740-5569 NR 39 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 13 PY 1998 VL 273 IS 11 BP 6057 EP 6065 DI 10.1074/jbc.273.11.6057 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZB597 UT WOS:000072488500014 PM 9497322 ER PT J AU Pan, CJ Lei, KJ Annabi, B Hemrika, W Chou, JY AF Pan, CJ Lei, KJ Annabi, B Hemrika, W Chou, JY TI Transmembrane topology of glucose-6-phosphatase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STORAGE-DISEASE TYPE-1A; ENDOPLASMIC-RETICULUM; ENZYME-DEFICIENT; RAT-LIVER; GENE; MUTATIONS; 1A AB Deficiency of microsomal glucose-6-phosphatase (G6Pase), the key enzyme in glucose homeostasis, causes glycogen storage disease type 1a, an autosomal recessive disorder. Characterization of the transmembrane topology of G6Pase should facilitate the identification of amino acid residues contributing to the active site and broaden our understanding of the effects of mutations that cause glycogen storage disease type 1a, Using N- and C-terminal tagged G6Pase, we show that in intact microsomes, the N terminus is resistant to protease digestion, whereas the C terminus is sensitive to such treatment. Our results demonstrate that G6Pase possesses an odd number of transmembrane helices, with its N and C termini facing the endoplasmic reticulum lumen and the cytoplasm, respectively. During catalysis, a phosphoryl enzyme intermediate is formed, and the phosphoryl acceptor in G6Pase is a His residue, Sequence alignment suggests that mammalian G6Pases, lipid phosphatases, acid phosphatases, and a vanadium-containing chloroperoxidase (whose tertiary structure is known) share a conserved phosphatase motif, Active-site alignment of the vanadium-containing chloroperoxidase and G6Pases predicts that Arg-83, His-119, and His-176 in G6Pase contribute to the active site and that His-176 is the residue that covalently binds the phosphoryl moiety during catalysis, This alignment also predicts that Arg-83, His-119, and His-176 reside on the same side of the endoplasmic reticulum membrane, which is supported by the recently predicted nine-transmembrane helical model for G6Pase. We have previously shown that Arg-83 is involved in positioning the phosphate during catalysis and that His-119 is essential for G6Pase activity. Here we demonstrate that substitution of His-176 with structurally similar or dissimilar amino acids inactivates the enzyme, suggesting that His-176 could be the phosphoryl acceptor in G6Pase during catalysis. C1 NICHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. Univ Amsterdam, EC Slater Inst Biochem Res, NL-1018 TV Amsterdam, Netherlands. RP Chou, JY (reprint author), NICHD, Heritable Disorders Branch, NIH, Bldg 10,Rm 9S241, Bethesda, MD 20892 USA. NR 33 TC 120 Z9 122 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 13 PY 1998 VL 273 IS 11 BP 6144 EP 6148 DI 10.1074/jbc.273.11.6144 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZB597 UT WOS:000072488500025 PM 9497333 ER PT J AU Sweeney, HL Rosenfeld, SS Brown, F Faust, L Smith, J Xing, J Stein, LA Sellers, JR AF Sweeney, HL Rosenfeld, SS Brown, F Faust, L Smith, J Xing, J Stein, LA Sellers, JR TI Kinetic tuning of myosin via a flexible loop adjacent to the nucleotide binding pocket SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOTOR DOMAIN; CHIMERIC SUBSTITUTIONS; ENZYMATIC-ACTIVITIES; HEAVY-MEROMYOSIN; SKELETAL-MUSCLE; CARDIAC MYOSIN; ACTIN; SUBFRAGMENT-1; SITE; PROTEINS AB A surface loop (25/50-kDa loop) near the nucleotide pocket of myosin has been proposed to be an important element in determining the rate of ADP release from myosin, and as a consequence, the rate of actin-myosin filament sliding (Spudich, J. A. (1991) Nature 372, 515-518). To test this hypothesis, loops derived from different myosin II isoforms that display a range of actin filament sliding velocities were inserted into a smooth muscle myosin backbone. Chimeric myosins were produced by baculovirus/Sf9 cell expression. Although the nature of this loop affected the rate of ADP release (up to 9-fold), in vitro motility (2.7-fold), and the V-max of actin-activated ATPase activity (up to a-fold), the properties of each chimera did not correlate with the relative speed of the myosin from which the loop was derived. Rather, the rate of ADP release was a function of loop size/flexibility with the larger loops giving faster rates of ADP release. The rate of actin filament translocation was altered by the rate of ADP release, but was not solely determined by it. Through a combination of solute quenching and transient fluorescence measurements, it is concluded that, as the loop gets smaller, access to the nucleotide pocket is more restricted. ATP binding becomes less favored, and ADP binding becomes more favored, In addition, the rate of ATP hydrolysis is slowed. C1 Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA. Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. Univ Alabama Birmingham, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA. SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA. NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Univ Penn, Sch Med, Dept Physiol, 3700 Hamilton Walk, Philadelphia, PA 19104 USA. EM lsweeney@mail.med.upenn.edu RI Sweeney, H Lee/F-1862-2010 FU NIAMS NIH HHS [AR-35661] NR 45 TC 186 Z9 186 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 13 PY 1998 VL 273 IS 11 BP 6262 EP 6270 DI 10.1074/jbc.273.11.6262 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZB597 UT WOS:000072488500044 PM 9497352 ER PT J AU Kang, SW Chae, HZ Seo, MS Kim, KH Baines, IC Rhee, SG AF Kang, SW Chae, HZ Seo, MS Kim, KH Baines, IC Rhee, SG TI Mammalian peroxiredoxin isoforms can reduce hydrogen peroxide generated in response to growth factors and tumor necrosis factor-alpha SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID THIOL-SPECIFIC ANTIOXIDANT; NF-KAPPA-B; ALKYL HYDROPEROXIDE REDUCTASE; MOUSE OSTEOBLASTIC CELLS; ATP-DEPENDENT PROTEASE; GLUTATHIONE-PEROXIDASE; SACCHAROMYCES-CEREVISIAE; SALMONELLA-TYPHIMURIUM; TRANSCRIPTION FACTOR; SIGNAL-TRANSDUCTION AB Mammalian tissues express three immunologically distinct peroxiredoxin (Prx) proteins (Prx I, II, and III), which are the products of distinct genes. With the use of recombinant proteins Prx I, II, and III, all have now been shown to possess peroxidase activity and to rely on Trx as a source of reducing equivalents for the reduction of H2O2. Prx I and II are cytosolic proteins, whereas Prx III is localized in mitochondria. Transient overexpression of Prx I or II in cultured cells showed that they were able to eliminate the intracellular H2O2 generated in response to growth factors. Moreover, the activation of nuclear factor kappa B (NF kappa B) induced by extracellularly added H2O2 or tumor necrosis factor-alpha was blocked by overproduction of Prx II. These results suggest that, together with glutathione peroxidase and catalase, Prx enzymes Likely play an important role in eliminating peroxides generated during metabolism. In addition, Prx I and II might participate in the signaling cascades of growth factors and tumor necrosis factor-alpha by regulating the intracellular concentration of H2O2. C1 NHLBI, Lab Cell Signalling, NIH, Bethesda, MD 20892 USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Rhee, SG (reprint author), NHLBI, Lab Cell Signalling, NIH, Bldg 3,Rm 122, Bethesda, MD 20892 USA. NR 46 TC 529 Z9 551 U1 3 U2 11 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 13 PY 1998 VL 273 IS 11 BP 6297 EP 6302 DI 10.1074/jbc.273.11.6297 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZB597 UT WOS:000072488500049 PM 9497357 ER PT J AU Kang, SW Baines, IC Rhee, SG AF Kang, SW Baines, IC Rhee, SG TI Characterization of a mammalian peroxiredoxin that contains one conserved cysteine SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALKYL HYDROPEROXIDE REDUCTASE; THIOL-SPECIFIC ANTIOXIDANT; SALMONELLA-TYPHIMURIUM; THIOREDOXIN REDUCTASE; ESCHERICHIA-COLI; NADH PEROXIDASE; SULFENIC ACID; REDOX CENTER; PURIFICATION; CLONING AB A new type of peroxidase enzyme, named thioredoxin peroxidase (TPx), that reduces H2O2 with the use of electrons from thioredoxin and contains two essential cysteines was recently identified. TPx homologs, termed peroxiredoxin (Prx), have also been identified and include several proteins, designated 1-Cys Prx, that contain only one conserved cysteine, Recombinant human 1-Cys Prx expressed in and purified from Escherichia coli has now been shown to reduce H2O2 with electrons provided by dithiothreitol. Furthermore, human 1-Cys Prx transiently expressed in NIH 3T3 cells was able to remove intracellular H2O2 generated in response either to the addition of exogenous H2O2 or to treatment with platelet-derived growth factor. The conserved Cys(47)-SH group was shown to be the site of oxidation by H2O2. Thus, mutation of Cys(47) to serine abolished peroxidase activity. Moreover, the oxidized intermediate appears to be Cys-SOH. In contrast to TPx, in which one of the two conserved cysteines is oxidized to Cys-SOH and then immediately reacts with the second conserved cysteine of the second subunit of the enzyme homodimer to form an intermolecular disulfide, the Cys-SOH of 1-Cys Prx does not form a disulfide. Neither thioredoxin, which reduces the disulfide of TPx, nor glutathione, which reduces the Cys-SeOH of oxidized glutathione peroxidase, was able to reduce the Cys-SOH of 1-Cys Prx and consequently could not support peroxidase activity. Human 1-Cys Prx was previously shown to exhibit a low level of phospholipase A(2) activity at an acidic pH; the enzyme was thus proposed to be lysosomal, and Ser(32) was proposed to be critical for lipase function. However, the mutation of Ser(32) or Cys(47) has now been shown to have no effect on the lipase activity of 1-Cys Prx, which was also shown to be a cytosolic protein. Thus, the primary cellular function of 1-Cys Prx appears to be to reduce peroxides with the use of electrons provided by an as yet unidentified source; the enzyme therefore represents a new type of peroxidase. C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Rhee, SG (reprint author), NHLBI, Lab Cell Signaling, NIH, Bldg 3,Room 122, Bethesda, MD 20892 USA. NR 33 TC 332 Z9 344 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 13 PY 1998 VL 273 IS 11 BP 6303 EP 6311 DI 10.1074/jbc.273.11.6303 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZB597 UT WOS:000072488500050 PM 9497358 ER PT J AU Sadler, BR Chae, K Ishaq, KS Korach, KS AF Sadler, BR Chae, K Ishaq, KS Korach, KS TI Separation of indenestrol A and B isomers and enantiomers by high-performance liquid chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE enantiomer separation; indenestrols; sterols ID DIETHYLSTILBESTROL METABOLITES; ANALOGS; PROBES; BINDING AB High-performance liquid chromatography (HPLC) methods have been developed for the separation of substituted indenestrol A and B isomers on different columns. The isomers were separated by normal-phase liquid chromatography with a silica gel column. Enantiomers of these compounds were separated by chiral HPLC and the most successful separations were achieved with a Chiralcel OJ column. Published by Elsevier Science B.V. C1 NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Sch Pharm, Dept Med Chem, Chapel Hill, NC 27599 USA. RP Chae, K (reprint author), NIEHS, Reprod & Dev Toxicol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 11 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD MAR 13 PY 1998 VL 799 IS 1-2 BP 117 EP 124 DI 10.1016/S0021-9673(97)01060-1 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA ZD766 UT WOS:000072721600012 PM 9550104 ER PT J AU Zheng, M Aslund, F Storz, G AF Zheng, M Aslund, F Storz, G TI Activation of the OxyR transcription factor by reversible disulfide bond formation SO SCIENCE LA English DT Article ID ESCHERICHIA-COLI; NEGATIVE MUTANTS; DNA-BINDING; GLUTATHIONE; STABILIZATION; REACTIVITY; REGULATOR; CHEMISTRY; PROTEINS; STRESS AB The OxyR transcription factor is sensitive to oxidation and activates the expression of antioxidant genes in response to hydrogen peroxide in Escherichia coli. Genetic and biochemical studies revealed that OxyR is activated through the formation of a disulfide bond and is deactivated by enzymatic reduction with glutaredoxin 1 (Grx1). The gene encoding Grx1 is regulated by OxyR, th us providing a mechanism for autoregulation. The redox potential of OxyR was determined to be -185 millivolts, ensuring that OxyR is reduced in the absence of stress. These results represent an example of redox signaling through disulfide bond formation and reduction. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Storz, G (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. OI Storz, Gisela/0000-0001-6698-1241 NR 35 TC 755 Z9 779 U1 4 U2 45 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAR 13 PY 1998 VL 279 IS 5357 BP 1718 EP 1721 DI 10.1126/science.279.5357.1718 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZB612 UT WOS:000072490000055 PM 9497290 ER PT J AU Misra, RR Smith, GT Waalkes, MP AF Misra, RR Smith, GT Waalkes, MP TI Evaluation of the direct genotoxic potential of cadmium in four different rodent cell lines SO TOXICOLOGY LA English DT Article ID CHINESE-HAMSTER CELLS; CULTURED-MAMMALIAN-CELLS; ISOLATED RAT HEPATOCYTES; METALLOTHIONEIN GENE; DNA-SYNTHESIS; METAL-IONS; EXPRESSION; ZINC; INDUCTION; CHLORIDE AB Cadmium is a toxic environmental contaminant that is carcinogenic in humans and laboratory animals. Although the mechanism underlying cadmium carcinogenesis has not yet been determined experimental evidence suggests that the stress-inducible, metal-binding proteins, metallothioneins, may mediate organ specificity. In the present study, four different rodent cell lines (Chinese hamster ovary cells, rat L6 myoblast cells, rat Clone 9 liver cells, and rat TRL 1215 liver cells) were exposed to 0, 1, 5, 10, 50, or 100 mu M CdCl2 and monitored for evidence of direct DNA damage. A microfiltration assay was used to measure DNA strand breaks and a filter-binding assay was used to measure DNA-protein crosslinks, two lesions that have been associated with cadmium exposure and may mediate genotoxicity of the metal. Although variability in sensitivity to DNA damage was evident between the different cell lines, in all of the cell lines tested, increases in DNA damage were observed only at cadmium doses that completely arrested cell growth. In addition, in three of the four cell lines tested, induction of metallothionein had no substantial protective effect against cadmium-induced cytotoxicity or genotoxicity. While protection against cadmium-induced DNA strand breakage with metallothionein preinduction was observed in the TRL 1215 rat liver cells, metallothionein preinduction did not protect against cadmium-induced DNA-protein crosslinking in that cell line. Taken together, our results support the hypothesis that cadmium is not directly genotoxic. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 NCI, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, Div Basic Sci,Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Misra, RR (reprint author), NCI, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, Div Basic Sci,Frederick Canc Res & Dev Ctr, Bldg 538,Room 205E, Frederick, MD 21702 USA. NR 38 TC 81 Z9 88 U1 1 U2 7 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD MAR 13 PY 1998 VL 126 IS 2 BP 103 EP 114 DI 10.1016/S0300-483X(98)00003-1 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA ZP171 UT WOS:000073724400003 PM 9620542 ER PT J AU Carr, PA Wenner, P AF Carr, PA Wenner, P TI Calcitonin gene-related peptide: distribution and effects on spontaneous rhythmic activity in embryonic chick spinal cord SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE locomotion; neuropeptide; development; motor neuron; in vitro; immunohistochemistry ID DORSAL-ROOT GANGLION; GALLUS-GALLUS-DOMESTICUS; CGRP MESSENGER-RNAS; SUBSTANCE-P; MOTOR-ACTIVITY; ALPHA-CGRP; RAT; RELEASE; NEURONS; HORN AB Immunohistochemical and in vitro electrophysiological techniques were utilized to examine the distribution and possible role of calcitonin gene-related peptide (CGRP) in the spinal cord of the developing chick. CGRP-like immunoreactivity first appeared in the lateral motor column of the lumbosacral spinal cord at embryonic day 6 followed by the emergence of fiber immunoreactivity in the dorsal horn at embryonic day 11. A rostrocaudal survey of the cervical to lumbosacral spinal cord in embryonic day 18 chick demonstrated robust CGRP-like immunoreactivity at all levels in both putative motor neurons and dorsal horn fibers. Additionally, small immunoreactive lamina VII neurons were observed in sections of lumbosacral cord. In the embryonic day 10 (E10) in vitro reduced spinal cord preparation, bath application of the calcitonin gene-related peptide antagonist human alpha-CGRP fragment 8-37 decreased the frequency and increased the duration of episodes of spontaneously occurring rhythmic activity. Conversely, application of alpha or beta forms of calcitonin gene-related peptide increased the frequency of the rhythmic episodes. The electrophysiological results suggest there is a constitutive release of calcitonin gene-related peptide contributing to the spontaneous rhythmic activity. Immunohistochemical results from E10 animals suggest that CGRP-like immunoreactive putative motoneurons may be the source of the released CGRP. (C) 1998 Elsevier Science B.V. C1 Wright State Univ, Dept Anat, Dayton, OH 45435 USA. NINDS, Sect Dev Neurobiol, Neural Control Lab, NIH, Bethesda, MD 20892 USA. RP Carr, PA (reprint author), Wright State Univ, Dept Anat, 3640 Colonel Glenn Highway, Dayton, OH 45435 USA. OI Wenner, Peter/0000-0002-7072-2194 NR 48 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD MAR 12 PY 1998 VL 106 IS 1-2 BP 47 EP 55 DI 10.1016/S0165-3806(97)00191-0 PG 9 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA ZH101 UT WOS:000073072200005 ER PT J AU Ma, W Pancrazio, JJ Coulombe, M Dumm, J Sathanoori, RS Barker, JL Kowtha, VC Stenger, DA Hickman, JJ AF Ma, W Pancrazio, JJ Coulombe, M Dumm, J Sathanoori, RS Barker, JL Kowtha, VC Stenger, DA Hickman, JJ TI Neuronal and glial epitopes and transmitter-synthesizing enzymes appear in parallel with membrane excitability during neuroblastoma x glioma hybrid differentiation SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE NG108-15 cell line; serum-free medium; excitability; patch-clamp; neural protein; neurotransmitter enzyme; bromodeoxyuridine; proliferation; differentiation ID NG108-15 CELLS; SYNAPSE FORMATION; DEFINED MEDIUM; NEURAL TUMOR; PROLIFERATION; MODULATION; INVIVO; CYCLE; LINE AB The membrane excitability and the presence of neural proteins, including neuronal and glial markers and neurotransmitter-synthesizing enzymes, were examined in parallel while the NG108-15 cell line was maintained in a serum-free medium. Whole-cell recordings in voltage-clamp or current-clamp configurations were used to evaluate the membrane excitability, and immunostaining was done with a panel of well-characterized antibodies against NSE, NF150, S-100 beta, GFAP, ChAT and TH. Culture for 4 to 10 days led to a striking rise in neurite outgrowth, electrical excitability and expression of neural proteins in type I neuron-like cells, which were of both neuronal and glial character, and expressed both cholinergic and adrenergic traits. After about 2 weeks, type II cells which lack neurite processes began to emerge. The type II cells proliferated, as revealed by BrdU uptake, and gradually overgrew differentiated cell types. They exhibited little or no membrane excitability and absence of immunoreactivity for the neuronal and glial specific proteins tested. These measurements indicate that the presence of these neural proteins at crucial stages of membrane excitability development is an important characteristic of NG108-15 cell differentiation, providing insights into the neural development and the reversible nature of neoplasia in the nervous system. (C) 1998 Elsevier Science B.V. C1 Sci Applicat Int Corp, Biotechnol Res & Applicat Div, Rockville, MD 20850 USA. NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA. RP Ma, W (reprint author), Sci Applicat Int Corp, Biotechnol Res & Applicat Div, 6 Taft Court,Suite 300, Rockville, MD 20850 USA. RI Pancrazio, Joseph/M-3206-2015 OI Pancrazio, Joseph/0000-0001-8276-3690 NR 27 TC 23 Z9 24 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD MAR 12 PY 1998 VL 106 IS 1-2 BP 155 EP 163 DI 10.1016/S0165-3806(97)00208-3 PG 9 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA ZH101 UT WOS:000073072200016 ER PT J AU Schutz, B Schafer, MKH Eiden, LE Weihe, E AF Schutz, B Schafer, MKH Eiden, LE Weihe, E TI Vesicular amine transporter expression and isoform selection in developing brain, peripheral nervous system and gut SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE VMAT2; VMAT1; VAChT; chemical coding; autonomic development; monoaminergic ontogeny ID EMBRYONIC SYMPATHETIC-GANGLIA; CHROMAFFIN CELL PLASTICITY; MONOAMINE TRANSPORTER; SYMPATHOADRENAL LINEAGE; ACETYLCHOLINE TRANSPORTER; MONOCLONAL-ANTIBODIES; ENDOCRINE-CELLS; NEURAL CREST; STEM-CELLS; NEURONS AB The vesicular monoamine transporters VMAT1 and VMAT2 are essential components of monoaminergic neurons and endocrine cells whose expression in development may provide insight into lineage pathways for chemical coding in the diffuse neuroendocrine system. Thus, the brain is a compartment in which only monoaminergic neurons are generated, the gut epithelium generates only endocrine monoamine-containing cells, and the neural crest produces both autonomic monoaminergic neurons and endocrine/paracrine monoaminergic cells. Selection of either the VMAT1 or VMAT2 isoform was examined in these three compartments during development. In the central nervous system VMAT2, but not VMAT1, was expressed in neuroepithelial cells by embryonic day 12 (E12), and all major monoaminergic cell groups by E14. Thalamocortical and hypothalamic neurons that do not express VMAT2 in adulthood were transiently VMAT2-positive from E16 to postnatal day 6 (P6). EC cells of the gut expressed exclusively VMAT1 from E19 on, while histamine-containing enterochromaffin-like (ECL) cells of the stomach expressed only VMAT2 by E19 and throughout postnatal development. VMAT2 and the vesicular acetylcholine transporter VAChT were co-expressed in early development of the primary sympathetic chain as well as in the cranial parasympathetic ganglia. VAChT was progressively restricted to a small population of VMAT2-negative post-ganglionic neurons in the adult sympathetic chain, while VMAT2 expression persisted in sympathetic principal ganglion and SIF cells but was eventually extinguished in cranial parasympathetic ganglia. VMAT1 was co-expressed with VAChT and VMAT2 mRNA in the primary sympathetic chain on E12, but progressively restricted to small intensely fluorescent (SIF) and chromaffin cells thereafter. Thus, expression of the vesicular amine transporters appropriate for chemical coding of brain neurons and gut endocrine cells are pre-determined developmentally. In contrast, the neural crest-derived sympathoadrenal and neural crest-derived parasympathetic cell groups examined here initially co-express two or more vesicular amine transporters, followed by extinction of the inappropriate transporter(s) later in development. Some neural crest-derived neuroendocrine cell populations continue to express both isoforms of VMAT even in adulthood. Lineage distinctions in ontogeny of vesicular amine transporter expression in brain, gut and autonomic nervous system make it likely that the same genes are regulated differently in the autonomic nervous system compared to brain and gut. (C) 1998 Elsevier Science B.V. C1 Univ Marburg, Dept Anat & Cell Biol, D-3550 Marburg, Germany. NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Eiden, LE (reprint author), Bldg 36,Room 3A-10,36 Convent Dr,MSC 4090, Bethesda, MD 20892 USA. EM eiden@codon.nih.gov OI Eiden, Lee/0000-0001-7524-944X NR 37 TC 43 Z9 43 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD MAR 12 PY 1998 VL 106 IS 1-2 BP 181 EP 204 DI 10.1016/S0165-3806(97)00196-X PG 24 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA ZH101 UT WOS:000073072200019 ER PT J AU Shippenberg, TS LeFevour, A Thompson, AC AF Shippenberg, TS LeFevour, A Thompson, AC TI Sensitization to the conditioned rewarding effects of morphine and cocaine: Differential effects of the K-opioid receptor agonist U69593 SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE behavioral sensitization, morphine; cocaine; K-opioid receptor ID BEHAVIORAL SENSITIZATION; EXTRACELLULAR DOPAMINE; NUCLEUS-ACCUMBENS; TEMPORAL CHARACTERISTICS; EXPRESSION; SYSTEMS; RATS; DEPENDENCE; TOLERANCE; OPIATE AB The ability of the kappa-opioid receptor agonist U69593 to attenuate the sensitization and cross-sensitization which develops to the conditioned rewarding effects of morphine and cocaine was examined using an unbiased place-preference conditioning procedure. The influence of U69593 treatment upon sensitization and cross-sensitization to cocaine was also assessed. Doses of morphine (1.0-5.0 mg kg(-1)) which failed to produce a conditioned response in drug-naive rats produced marked preferences for the drug-paired place in animals which had previously received once daily injections of morphine (5.0 mg kg(-1); s.c.) or cocaine (10.0 mg kg(-1); i.p.) for 5 days. Morphine-induced place preferences also occurred in animals which had received morphine in combination with U69593 (0.04-0.32 mg kg(-1); s.c.) on either days 3-5 or 1-5 of the morphine treatment regimen. In contrast, morphine failed to produce significant conditioning in animals which had received U69593 with cocaine for 5 days. Doses of cocaine (1.0-5.0 mg kg(-1)) which did not produce a conditioned response in naive rats produced preferences for the drug-paired place in animals which had received once daily injections of cocaine (10.0 mg kg(-1) day(-1) x 5 days: i.p.) or morphine (5.0 mg kg(-1) day(-1) x 5 days; s.c.). No enhancement of cocaine-induced conditioning occurred in animals which had received U69593 on days 3-5 or on days 1-5 of the five-day cocaine treatment. In animals, however, which had received U69593 with morphine for 5 days, an enhanced response to cocaine was still seen. These findings confirm that sensitization and cross-sensitization develop to the conditioned rewarding effects of cocaine and morphine. They also indicate that the ability of a kappa-opioid receptor agonist to prevent the development of these sensitized responses depends on the sensitizing agent employed. U69593 prevents sensitization and cross-sensitization induced by cocaine. but does not modify morphine-induced sensitization or the cross-sensitization which develops to cocaine after morphine administration. Published by Elsevier Science B.V. C1 NIA, Integrat Neurosci Unit, Behav Neurosci Branch, Div Intramural Res, Baltimore, MD 21224 USA. RP Shippenberg, TS (reprint author), NIA, Integrat Neurosci Unit, Behav Neurosci Branch, Div Intramural Res, POB 5180, Baltimore, MD 21224 USA. NR 39 TC 65 Z9 67 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD MAR 12 PY 1998 VL 345 IS 1 BP 27 EP 34 DI 10.1016/S0014-2999(97)01614-2 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZJ636 UT WOS:000073236600003 PM 9593590 ER PT J AU Lewin, AH Sun, GB Fudala, L Navarro, H Zhou, LM Popik, P Faynsteyn, A Skolnick, P AF Lewin, AH Sun, GB Fudala, L Navarro, H Zhou, LM Popik, P Faynsteyn, A Skolnick, P TI Molecular features associated with polyamine modulation of NMDA receptors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID D-ASPARTATE RECEPTOR; MK-801 BINDING; COMPLEX; GLYCINE; ACID; REQUIREMENT; SITE AB The effect of 1,3-diamines on basal and spermine-stimulated [H-3]MK-801 binding was investigated. Systematic variations in the molecular parameters revealed that, in general, lipophilic 1,3-diamines inhibited and hydrophilic 1,3-diamines enhanced [H-3]MK-801 binding in the nominal absence of glutamate and glycine. Furthermore, 1,3-diamines which were highly monoprotonated at physiologic pH were more effective in modulating basal binding (at 100 mu M 1,3-diamine) than analogues which were mostly diprotonated or unprotonated. Finally, the internuclear distance between the amino nitrogens and the extent of modulation of basal [H-3]MK-801 binding were correlated. Similar, but more modest, effects were seen for spermine-enhanced [H-3]MK-801 binding. These results are consistent with the existence of two polyamine binding sites associated with the NMDA receptor complex. One of the sites appears to preferentially recognize lipophilic substances while the other favors hydrophilic materials. Both sites appear to recognize polyamines with at least one charged (protonated) amino group and one uncharged amino group. The distance between amino groups is a determining factor as well. C1 Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Lewin, AH (reprint author), Res Triangle Inst, Med Chem Bldg,Room 283,POB 12194, Res Triangle Pk, NC 27709 USA. EM ahl@rti.org RI Popik, Piotr/R-5383-2016 OI Popik, Piotr/0000-0003-0722-1263 FU NIDA NIH HHS [5 R01 DAO 9038, R01 DA009038, R01 DA009038-03] NR 24 TC 16 Z9 18 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 12 PY 1998 VL 41 IS 6 BP 988 EP 995 DI 10.1021/jm9707129 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA ZC178 UT WOS:000072548600021 PM 9526573 ER PT J AU Caritis, S Sibai, B Hauth, J Lindheimer, MD Klebanoff, M Thom, E VanDorsten, P Landon, M Paul, R Miodovnik, M Meis, P Thurnau, G AF Caritis, S Sibai, B Hauth, J Lindheimer, MD Klebanoff, M Thom, E VanDorsten, P Landon, M Paul, R Miodovnik, M Meis, P Thurnau, G CA Natl Inst Child Hlth Human Dev Network Materna TI Low-dose aspirin to prevent preeclampsia in women at high risk SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PREGNANCY-INDUCED HYPERTENSION; PRE-ECLAMPSIA; FETAL GROWTH; PROSTACYCLIN; THERAPY AB Background Whether low-dose aspirin prevents preeclampsia is unclear. It is not recommended as prophylaxis in women at low risk for preeclampsia but may reduce the incidence of the disease in women at high risk. Methods We conducted a double-blind, randomized, placebo-controlled trial in four groups of pregnant women at high risk for preeclampsia, including 471 women with pregestational insulin-treated diabetes mellitus, 774 women with chronic hypertension, 688 women with multifetal gestations, and 606 women who had had preeclampsia during a previous pregnancy. The women were enrolled between gestational weeks 13 and 26 and received either 60 mg of aspirin or placebo daily. Results Outcome data were obtained on all but 36 of the 2539 women who entered the study. The incidence of preeclampsia was similar in the 1254 women in the aspirin group and the 1249 women in the placebo group (aspirin, 18 percent; placebo, 20 percent; P=0.23). The incidences in the aspirin and placebo groups for each of the four high-risk categories were also similar: for women with pregestational diabetes mellitus, the incidence was 18 percent in the aspirin group and 22 percent in the placebo group (P=0.38); for women with chronic hypertension, 26 percent and 25 percent (P=0.66); for those with multifetal gestations, 12 percent and 16 percent (P=0.10); and for those with preeclampsia during a previous pregnancy, 17 percent and 19 percent (P=0.47). In addition, the incidences of perinatal death, preterm birth, and infants small for gestational age were similar in the aspirin and placebo groups. Conclusions In our study, low-dose aspirin did not reduce the incidence of preeclampsia significantly or improve perinatal outcomes in pregnant women at high risk for preeclampsia. (C) 1998, Massachusetts Medical Society. C1 Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA 15260 USA. Univ Tennessee, Dept Obstet & Gynecol, Memphis, TN 38103 USA. Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Med Univ S Carolina, Dept Obstet & Gynecol, Charleston, SC 29425 USA. Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Univ So Calif, Dept Obstet & Gynecol, Los Angeles, CA 90089 USA. Univ Cincinnati, Dept Obstet & Gynecol, Cincinnati, OH 45221 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Obstet & Gynecol, Winston Salem, NC USA. Univ Oklahoma, Dept Obstet & Gynecol, Oklahoma City, OK USA. NICHHD, Bethesda, MD 20892 USA. George Washington Univ, Ctr Biostat, Washington, DC USA. RP Caritis, S (reprint author), Magee Womens Hosp, Dept Obstet Gynecol & Reprod Sci, 300 Halket St,Rm 2229, Pittsburgh, PA 15213 USA. OI caritis, steve/0000-0002-2169-0712 FU NICHD NIH HHS [HD19897, HD21410, HD21414] NR 18 TC 329 Z9 340 U1 0 U2 6 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 12 PY 1998 VL 338 IS 11 BP 701 EP 705 DI 10.1056/NEJM199803123381101 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA ZB546 UT WOS:000072483400001 PM 9494145 ER PT J AU Palumbo, PE Raskino, C Fiscus, S Pahwa, S Fowler, MG Spector, SA Englund, JA Baker, CJ AF Palumbo, PE Raskino, C Fiscus, S Pahwa, S Fowler, MG Spector, SA Englund, JA Baker, CJ TI Predictive value of quantitative plasma HIV RNA and CD4(+) lymphocyte count in HIV-infected infants and children SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MARKERS; VIRUS; THERAPY AB Context.-Pediatric human immunodeficiency virus (HIV) infection has unique viral pathogenetic features that preclude routine extrapolation from adult studies and require specific analysis. Objectives.-To evaluate the prognostic value of 2 key laboratory markers-plasma RNA and CD4(+) lymphocyte count-for HIV disease progression in infants and children and to establish targeted values for optimal outcome. Design.-Data from a cohort of 566 infants and children who participated in a randomized, placebo-controlled trial of nucleoside reverse transcriptase inhibitors (ACTG 152) were analyzed. The trial was conducted between 1991 and 1995 and enrolled a heterogenous cohort of antiretroviral therapy-naive children (age, 3 months to 18 years); patients had a median follow-up of 32 months. Main Outcome Measures.-The trial clinical end points consisted of time to first HIV disease progression (growth failure, decline in neurologic or neurodevelopmental function, opportunistic infections) or death. Results.-Baseline plasma RNA levels were high (age group medians, 5x10(4) to >10(6) copies/mL), and both baseline RNA and CD4(+) lymphocyte count were independently predictive of subsequent clinical course. Risk reduction for disease progression between 49% and 64% was observed for each log(10) reduction in baseline RNA and was linear without suggestion of a threshold or age effect. Disease progression predictive power was enhanced by the combined use of plasma RNA and CD4(+) cell count, Marker values of less than 10 000 copies/mL for plasma RNA and greater than 500 x 10(6)/L (<6.5 years of age) or greater than 200 x 10(6)/L (>6.5 years) for CD4(+) cell count were associated with a 2-year disease progression rate of less than 5%. Conclusions.-Two key laboratory markers-plasma RNA and CD4(+) lymphocyte count-are independent predictors of clinical course among HIV-infected infants and children. The linear, age-independent relationship between log(10) plasma RNA and relative risk of disease progression strongly supports therapeutic efforts to achieve plasma virus levels as low as possible. C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pediat, Newark, NJ 07103 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA. NYU, Sch Med, N Shore Univ Hosp, Dept Pediat, Manhasset, NY USA. NIAID, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Dept Microbiol & Immunol, Houston, TX 77030 USA. RP Palumbo, PE (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pediat, 185 S Orange Ave, Newark, NJ 07103 USA. NR 24 TC 152 Z9 157 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 11 PY 1998 VL 279 IS 10 BP 756 EP 761 DI 10.1001/jama.279.10.756 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA ZA474 UT WOS:000072366900032 PM 9508151 ER PT J AU Banerjee, S Pieper, U Kapadia, G Pannell, LK Herzberg, O AF Banerjee, S Pieper, U Kapadia, G Pannell, LK Herzberg, O TI Role of the Omega-loop in the activity, substrate specificity, and structure of class A beta-lactamase SO BIOCHEMISTRY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; STAPHYLOCOCCUS-AUREUS PC1; ACYL-ENZYME INTERMEDIATE; BACILLUS-LICHENIFORMIS 749/C; REFINED CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; 6-BETA-BROMOPENICILLANIC ACID; CRYSTALLOGRAPHIC STRUCTURE; FOLDING PATHWAY; RESOLUTION AB The structure of class A beta-lactamases contains an Omega-loop associated with the active site, which carries a key catalytic residue, Glu166. A 16-residue Omega-loop deletion mutant of beta-lactamase from Staphylococcus aureus PCl, encompassing residues 163-178, was produced in order to examine the functional and structural role of the loop. The crystal structure was determined and refined at 2.3 Angstrom, and the kinetics of the mutant enzyme was characterized with a variety of beta-lactam antibiotics. In general, the wild-type beta-lactamase hydrolyzes penicillin compounds better than cephalosporins. In contrast, the deletion of the Omega-loop led to a variant enzyme that acts only on cephalosporins, including third generation compounds. Kinetic measurements and electrospray mass spectrometry revealed that the first and third generation cephalosporins form stable acyl-enzyme complexes, except for the chromogenic cephalosporin, nitrocefin, which after acylating the enzyme undergoes hydrolysis at a 1000-fold slower rate than that with wild-type beta-lactamase. Hydrolysis of the acyl-enzyme adducts is prevented because the deletion of the Omega-loop eliminates the deacylation apparatus comprising Glu166 and its associated nucleophilic water site. The crystal structure reveals that while the overall fold of the mutant enzyme is similar to that of the native beta-lactamase, local adjustments in the vicinity of the missing loop occurred. The altered beta-lactam specificity is attributed to these structural changes. In the native structure, the Omega-loop restricts the conformation of a beta-strand at the edge of the active site depression. Removal of the loop provides the beta-strand with a new degree of conformational flexibility, such that it is displaced inward toward the active site space. Modeled Michaelis complexes with benzylpenicillin and cephaloridine show that the perturbed conformation of the beta-strand is inconsistent with penicillin binding because of steric clashes between the beta-lactam side chain substituent and the beta-strand. In contrast, no clashes occur upon cephalosporin binding. Recognition of third generation cephalosporins is possible because the bulky side chain substituents of the beta-lactam ring typical of these compounds can be accommodated in the space freed by the deletion of the Omega-loop. C1 Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Herzberg, O (reprint author), Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, 9600 Gudelsky Dr, Rockville, MD 20850 USA. EM osnat@carb.nist.gov RI Pieper, Ursula/E-4444-2010 FU NIAID NIH HHS [R01-AI27175] NR 47 TC 56 Z9 59 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 MAR 10 PY 1998 VL 37 IS 10 BP 3286 EP 3296 DI 10.1021/bi972127f PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZC900 UT WOS:000072630300008 PM 9521648 ER PT J AU Khangulov, SV Gladyshev, VN Dismukes, GC Stadtman, TC AF Khangulov, SV Gladyshev, VN Dismukes, GC Stadtman, TC TI Selenium-containing formate dehydrogenase H from Escherichia coli: A molybdopterin enzyme that catalyzes formate oxidation without oxygen transfer SO BIOCHEMISTRY LA English DT Article ID ELECTRON-PARAMAGNETIC-RESONANCE; NICOTINIC-ACID HYDROXYLASE; RELEVANT ANALOG COMPLEXES; CLOSTRIDIUM-BARKERI; XANTHINE-OXIDASE; ATOM TRANSFER; MOLYBDENUM OXOTRANSFERASES; METHANOCOCCUS-VOLTAE; CRYSTAL-STRUCTURE; REACTION SYSTEM AB Formate dehydrogenase H, FDH(Se), from Escherichia coli contains a molybdopterin guanine dinucleotide cofactor and a selenocysteine residue in the polypeptide. Oxidation of C-13-labeled formate in O-18-enriched water catalyzed by FDH(Se) produces (CO2)-C-13 gas that contains no O-18-label, establishing that the enzyme is not a member of the large class of Mo-pterin-containing oxotransferases which incorporate oxygen from water into product. An unusual Mo center of the active site is coordinated in the reduced Mo(IV) state in a square pyramidal geometry to the four equatorial dithiolene sulfur atoms from a pair of pterin cofactors and a Se atom of the selenocysteine-140 residue [Boyington, J. C., Gladyshev, V. N., Khangulov, S. V., Stadtman, T. C., and Sun, P. D. (1997) Science 275, 1305-1308]. EPR spectroscopy of the Mo(V) state indicates a square pyramidal geometry analogous to that of the Mo(IV) center. The strongest ligand field component is likely the single axial Se atom producing a ground orbital configuration Mo(d(xy)). The Mo-Se bond was estimated to be covalent to the extent of 17-27% of the unpaired electron spin density residing in the valence 4s and 4p selenium orbitals, based on comparison of the scalar and dipolar hyperfine components to atomic Se-77. Two electron oxidation of formate by the Mo(IV) state converts Mo to the reduced Mo(IV) state with the formate proton, H-f(+), transferring to a nearby base Y-. Transfer of one electron to the Fe4S4 center converts Mo(IV) to the EPR detectable Mo(V) state. The Y- is located within magnetic contact to the [Mo-Se] center, as shown by its strong dipolar H-1(f) hyperfine couplings. Photolysis of the formate-induced Mo(V) state abolishes the H-1(f) hyperfine splitting from YHf, suggesting photoisomerization of this group or phototransfer of the proton to a more distant proton acceptor group A(-). The minor effect of photolysis on the Se-77-hyperfine interaction with [Se-77] selenocysteine suggests that the Y- group is not the Se atom, but instead might be the imidazole ring of the His141 residue which is located in the putative substrate-binding pocket close to the [Mo-Se] center. We propose that the transfer of H-f(+) from formate to the active site base Y- is thermodynamically coupled to two-electron oxidation of the formate molecule, thereby facilitating formation of CO2. Under normal physiological conditions, when electron flow is not limited by the terminal acceptor of electrons, the energy released upon oxidation of Mo(IV) centers by the Fe4S4 is used for deprotonation of YHf and transfer of H-f(+) against the thermodynamic potential. C1 Princeton Univ, Hoyt Lab, Dept Chem, Princeton, NJ 08544 USA. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Khangulov, SV (reprint author), Princeton Univ, Hoyt Lab, Dept Chem, Princeton, NJ 08544 USA. EM khang@chemvax.princeton.edu RI Dismukes, Gerard/I-4905-2012; Gladyshev, Vadim/A-9894-2013 OI Dismukes, Gerard/0000-0003-0155-0541; NR 57 TC 74 Z9 77 U1 2 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 10 PY 1998 VL 37 IS 10 BP 3518 EP 3528 DI 10.1021/bi972177k PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZC900 UT WOS:000072630300033 PM 9521673 ER PT J AU Clever, LH Colaianni, LA Davidoff, F Hoey, J Horton, R Lundberg, G Glass, R Nylenna, M Smith, R Utiger, R VanDer Weyden, M Woolf, P AF Clever, LH Colaianni, LA Davidoff, F Hoey, J Horton, R Lundberg, G Glass, R Nylenna, M Smith, R Utiger, R VanDer Weyden, M Woolf, P CA Int Comm Med Journal Editors TI Statement on project-specific industry support for research SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Editorial Material C1 Natl Lib Med, Bethesda, MD 20894 USA. Annals Internal Med, Philadelphia, PA 19106 USA. Lancet, New York, NY 10010 USA. Journal Amer Med Assoc, Chicago, IL 60610 USA. British Med Journal, London, England. New England Journal Med, Waltham, MA 02154 USA. Med Journal Australia, Sydney, NSW, Australia. Princeton Univ, Princeton, NJ 08544 USA. RP Clever, LH (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU CANADIAN MEDICAL ASSOCIATION PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD MAR 10 PY 1998 VL 158 IS 5 BP 615 EP 616 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA ZB655 UT WOS:000072494300029 ER PT J AU Srinivasan, G Kitsiou, AN Bacharach, SL Bartlett, ML Miller-Davis, C Dilsizian, V AF Srinivasan, G Kitsiou, AN Bacharach, SL Bartlett, ML Miller-Davis, C Dilsizian, V TI [F-18] fluorodeoxyglucose single photon emission computed tomography - Can it replace PET and thallium SPECT for the assessment of myocardial tomography SO CIRCULATION LA English DT Article DE myocardium; coronary disease; tomography; radioisotopes; nuclear medicine ID CORONARY-ARTERY DISEASE; LEFT-VENTRICULAR DYSFUNCTION; RADIONUCLIDE VENTRICULOGRAPHY; VIABLE MYOCARDIUM; WALL-MOTION; VIABILITY; TL-201; REINJECTION; REVASCULARIZATION; FEASIBILITY AB Background-New high-energy collimators for single photon emission computed tomography (SPECT) cameras have made imaging of positron-emitting tracers, such as [F-18]fluorodeoxyglucose ((18)FDG), possible. We examined differences between SPECT and PET technologies and between (18)FDG and thallium tracers to determine whether (18)FDG SPECT could be adopted for assessment of myocardial viability. Methods and Results-Twenty-eight patients with chronic coronary artery disease (mean left ventricular ejection fraction [LVEF]=33+/-15% at rest) underwent (18)FDG SPECT, (18)FDG PET, and thallium SPECT studies. Receiver operating characteristic curves showed overall good concordance between SPECT and PET technologies and thallium and (18)FDG tracers for assessing viability regardless of the level of (18)FDG PET cutoff used (40% to 60%). However, in the subgroup of patients with LVEF less than or equal to 25%, at 60% (18)FDG PET threshold value, thallium tended to underestimate myocardial viability. In a subgroup of regions with severe asynergy, there were considerably more thallium/(18)FDG discordances in the inferior wall than elsewhere (73% versus 27%, P<.001), supporting attenuation of thallium as a potential explanation for the discordant observations. When uptake of (18)FDG by SPECT and PET was compared in 137 segments exhibiting severely irreversible thallium defects (scarred by thallium), 59 (43%) were viable by (18)FDG PET, of which 52 (88%) were also viable by (18)FDG SPECT. However, of the 78 segments confirmed to be nonviable by (18)FDG PET, 57 (73%) were nonviable by (18)FDG SPECT (P<.001). Conclusion-Although (18)FDG SPECT significantly increases the sensitivity for detection of viable myocardium in tissue declared nonviable by thallium (to 88% of the sensitivity achievable by PET), it will occasionally (27% of the time) result in falsely identifying as viable tissue that has been identified as nonviable by both PET and thallium. C1 NHLBI, NIH, Cardiol Branch, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Bethesda, MD 20892 USA. RP Srinivasan, G (reprint author), NHLBI, NIH, Cardiol Branch, 10 Ctr Dr,MSC 1650,Bldg 10,Room 7B-15, Bethesda, MD 20892 USA. NR 29 TC 74 Z9 79 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 10 PY 1998 VL 97 IS 9 BP 843 EP 850 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ZA372 UT WOS:000072356900003 PM 9521332 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 Selective defect in nitric oxide synthesis may explain the impaired endothelium-dependent vasodilation in patients with essential hypertension SO CIRCULATION LA English DT Article DE receptors, adrenergic, beta; signal transduction; acetylcholine; nitric oxide; hypertension ID SIGNAL-TRANSDUCTION PATHWAY; VASCULAR RELAXATION; SMOOTH-MUSCLE; ACETYLCHOLINE; AORTA; HYPERPOLARIZATION; CALCIUM; HUMANS; CELLS; RATS AB Background-Patients with essential hypertension have impaired endothelial NO activity, but the mechanism underlying this abnormality is unknown. Methods and Results-To investigate whether the endothelial dysfunction of hypertensive patients is related to a selective defect in NO synthesis, we studied the forearm blood now responses to intra-arterial infusion of acetylcholine (7.5 to 30 mu g/min), an endothelial agonist linked to NO synthase through the Ca2+ signaling pathway, and isoproterenol (50 to 200 ng/min), a beta-adrenoceptor agonist that stimulates NO production by increasing intracellular cAMP, in 12 normotensive subjects and 12 hypertensive patients. The infusion of isoproterenol was repeated during the concurrent blockade of NO synthesis by N-G-monomethyl-L-arginine (L-NMMA; 4 mu mol/min). The vasodilator response to acetylcholine was significantly reduced in hypertensives compared with normotensives (maximum blood flow: 10.4+/-4.6 versus 14.4+/-3.7 mL . min(-1) . dL(-1); P=.008). However, the vasodilator effect of isoproterenol was similar in normotensives and hypertensives (maximum blood now: 14.4+/-5.4 versus 13.5+/-5 mL . min(-1) . dL(-1); P=.56) and was significantly (both P<.01) and equally blunted by L-NMMA in both groups (maximum blood now: 11+/-3 mL . min(-1). dL(-1) in normotensives versus 10.8+/-3.9 mL . min(-1) . dL(-1) in hypertensives; P=.77). The vasodilator response to sodium nitroprusside (0.8 to 3.2 mu g/min), an exogenous NO donor, was similar in both groups and was not modified by L-NMMA. Conclusions-Hypertensive patients have impaired endothelium-dependent vasodilation in response to acetylcholine but preserved NO activity in response to beta-adrenergic stimulation. These findings suggest that the endothelial dysfunction in essential hypertension is due to a selective abnormality of NO synthesis, probably related to a defect in the phosphatidylinositol/Ca2+ signaling pathway. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Panza, JA (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10,Room 7B-15, Bethesda, MD 20892 USA. EM panzaj@gwgate.nhlbi.nih.gov NR 36 TC 112 Z9 116 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 10 PY 1998 VL 97 IS 9 BP 851 EP 856 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ZA372 UT WOS:000072356900004 PM 9521333 ER PT J AU Feinstein, A Goldberg, TE Nowlin, B Weinberger, DR AF Feinstein, A Goldberg, TE Nowlin, B Weinberger, DR TI Types and characteristics of remote memory impairment in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE remote memory impairment; neocortical dysfunction; temporoparietal regions; schizophrenia ID RETROGRADE-AMNESIA; THOUGHT-DISORDER; ALZHEIMER TYPE; TEMPORAL-LOBE; DEMENTIA; ABNORMALITIES; AGE AB Remote memory, as the term is used in the present study, refers to semantic information or autobiographical information for events and facts that are thought to be stored in the neocortex. In schizophrenia, findings of abnormalities in remote memory have been reported. However, it is unclear whether these are due to retrieval factors or other factors (e.g. paucity of information, disorganized lexicosemantic representations). Furthermore, it is unclear whether there is a temporal gradient in remote memory. In the first study, we utilized a cueing procedure for semantic fluency in order to determine whether retrieval factors play a marked role in impairments. In comparing patients with schizophrenia to patients with affective disorder and normal controls, we found that cueing had an equivalent effect upon all groups, suggesting that marked retrieval deficits were not the primary determinant of poor performance in fluency. Furthermore, we found that semantic fluency was disproportionately impaired vis-a-vis phonologic fluency, suggesting that abnormalities may be greater in storage areas presumed to be in temporal parietal cortex rather than in prefrontal cortex (which has been associated with retrieval deficits). In the second study, we examined the temporal gradient of autobiographical memory in patients with schizophrenia and normal controls. Whereas normal controls exhibited high and equivalent performance across childhood, early adult, and recent memories, patients with schizophrenia exhibited a u-shaped profile perhaps unique in the neuropsychiatric literature. This may reflect a combination of secondary memory impairments which effect the acquisition of new information coupled to very mildly accelerated rate of forgetting, 'recency' effects, and/or inefficient encoding. Taken together, these studies provide further support for the notion that schizophrenia has a relatively unique pattern of neuropsychological deficit based on neocortical dysfunction that includes, though is not restricted to, temporoparietal regions. (C) 1998 Elsevier Science B.V. C1 NIMH, Clin Brain Disorders Branch, Intramural Res Program, Neurosci Ctr St Elizabeths, Washington, DC 20032 USA. RP Goldberg, TE (reprint author), NIMH, Clin Brain Disorders Branch, Intramural Res Program, Neurosci Ctr St Elizabeths, Washington, DC 20032 USA. EM goldbert@dirpc.nimh.nih.gov NR 23 TC 60 Z9 60 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 10 PY 1998 VL 30 IS 2 BP 155 EP 163 DI 10.1016/S0920-9964(97)00129-1 PG 9 WC Psychiatry SC Psychiatry GA ZD479 UT WOS:000072690100008 PM 9549779 ER PT J AU Wilder, KE Weinberger, DR Goldberg, TE AF Wilder, KE Weinberger, DR Goldberg, TE TI Operant conditioning and the orbitofrontal cortex in schizophrenic patients: unexpected evidence for intact functioning SO SCHIZOPHRENIA RESEARCH LA English DT Article ID DEFICITS; DYSFUNCTION AB Neuroimaging and neuropsychological studies have consistently implicated dorsolateral prefrontal cortex as abnormal in schizophrenia. However, other areas of frontal cortex have received far less attention. In particular, few studies have examined orbital frontal regions with other than olfactory tests. In the present study we wished to assess the functional capability of orbital frontal cortex using a test developed by Bechara et al. (1994) that assesses a subject's capacity to acquire a preference through reward and punishment, using a gambling task that involved gains and losses of play money. Thirty normal subjects and 12 patients with schizophrenia (three undifferentiated, eight paranoid, one schizoaffective) comprised the sample in the present study. We found that patients with schizophrenia exhibited a pattern of findings similar to that of normals and dissimilar to that of patients with known orbital frontal damage. In our study, both normal subjects and schizophrenic patients chose most frequently from decks of cards in which there were frequent rewards and infrequent penalties, as might be expected on the basis of operant conditioning literature. We also found that performance on this task was not correlated with tests of working memory or longterm memory, suggesting that the development of a preference may occur implicitly. Our findings also argue against a general deficit in schizophrenia, as performance on the gambling task appeared relatively uncompromised. (C) 1998 Elsevier Science B.V. C1 NIMH, Clin Brain Disorders Branch, IRP, NIH,Neurosci Ctr St Elizabeths, Washington, DC 20032 USA. RP Goldberg, TE (reprint author), NIMH, Clin Brain Disorders Branch, IRP, NIH,Neurosci Ctr St Elizabeths, Washington, DC 20032 USA. NR 21 TC 85 Z9 89 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 10 PY 1998 VL 30 IS 2 BP 169 EP 174 DI 10.1016/S0920-9964(97)00135-7 PG 6 WC Psychiatry SC Psychiatry GA ZD479 UT WOS:000072690100010 PM 9549781 ER PT J AU Philbin, EF Garg, R Danisa, K Denny, DM Gosselin, G Hassapoyannes, C Horney, A Johnstone, DE Lang, RM Ramanathan, K Safford, RE Sarma, RJ Weiss, R Williford, WO Fleg, JL AF Philbin, EF Garg, R Danisa, K Denny, DM Gosselin, G Hassapoyannes, C Horney, A Johnstone, DE Lang, RM Ramanathan, K Safford, RE Sarma, RJ Weiss, R Williford, WO Fleg, JL CA Digitalis Investigation Grp TI The relationship between cardiothoracic ratio and left ventricular ejection fraction in congestive heart failure SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ISOSORBIDE DINITRATE; DYSFUNCTION; MANAGEMENT; DETERMINANTS; HYDRALAZINE; DIAGNOSIS; MORTALITY; VARIABLES; THERAPY AB Background: Left ventricular ejection fraction (EF) is a valuable prognostic index in patients with congestive heart failure (CHF). Although EF can be readily measured, many clinicians use roentgenographic heart size as a clue to differentiate systolic from diastolic dysfunction, even in the absence of solid supportive data. Objective: To test the hypothesis that the cardiothoracic ratio (CTR) measured from the chest roentgenogram can be used to estimate left ventricular EF in individuals with CHF. Methods: To answer this question, the database of the Digitalis Investigation Group trial was used. The CTR, determined using the Danzer method, and quantitative EF, measured locally using angiographic, radionuclide, or 2-dimensional echocardiographic techniques, were compared in 7476 patients with clinical CHF (New York Heart Association functional classes I-IV) due to acquired left-sided cardiac disease of ischemic, hypertensive, idiopathic, and alcohol-related causes. Results: Mean (+/-SD) CTR for the cohort was 0.53 +/- .07. Mean (+/-SD) EF was 31.7% +/- 12.2%. A weak, negative correlation between CTR and EF was observed (r = -0.176). Similar findings were obtained when the results were stratified by cause of CHF, presence of clinically defined right ventricular dysfunction, and method of EF measurement. Categorical analysis failed to yield a CTR cutoff point that facilitated useful segregation of individuals with an EF greater than 35% or 35% and below; greater than 40% or 40% and below; and greater than 45% or 45% and below in any patient group. Conclusions: Although a weak, negative correlation exists between CTR and EF, this relationship does not allow for accurate determination of systolic function in individual patients with CHF. Considering the morbidity and mortality associated with CHF, and the clinical implications of systolic function in this syndrome, direct measurement of EF is recommended. C1 Harvard Univ, Sch Med, Boston, MA USA. Merck Medco Managed Care Inc, Montvale, NJ USA. Vet Affairs Med Ctr, Muskogee, OK USA. River Cities Cardiol, Jeffersonville, IN USA. Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada. WJB Dorn Vet Affairs Med Ctr, Columbia, SC USA. Dept Vet Affairs, Perry Point, MD USA. Victoria Gen Hosp, Halifax, NS B3H 2Y9, Canada. Univ Chicago Hosp, Chicago, IL 60637 USA. Vet Affairs Med Ctr, Memphis, TN USA. Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. Northridge Hosp, Med Ctr, Northridge, CA USA. Androscoggin Cardiol Associates, Auburn, ME USA. Francis Scott Key Med Ctr, Baltimore, MD 21224 USA. NIA, Baltimore, MD 21224 USA. RP Philbin, EF (reprint author), Henry Ford Hlth Syst, Sect Heart Failure & Heart Transplantat, Div Cardiovasc Med, 2799 W Grand Blvd, Detroit, MI 48202 USA. EM ephilbi1@hfhs.org FU NHLBI NIH HHS [1Y01-HC00110] NR 36 TC 26 Z9 32 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 9 PY 1998 VL 158 IS 5 BP 501 EP 506 DI 10.1001/archinte.158.5.501 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA ZA609 UT WOS:000072381800011 PM 9508228 ER PT J AU Lee, YS Hodoscek, M Brooks, BR Kador, PF AF Lee, YS Hodoscek, M Brooks, BR Kador, PF TI Catalytic mechanism of aldose reductase studied by the combined potentials of quantum mechanics and molecular mechanics SO BIOPHYSICAL CHEMISTRY LA English DT Article DE aldose reductase; NADPH; catalytic mechanism; proton donor; combined potentials; QM/MM ID SITE-DIRECTED MUTAGENESIS; DIABETIC COMPLICATIONS; DYNAMICS SIMULATIONS; ALDEHYDE REDUCTASE; CRYSTAL-STRUCTURE; MUTANT ENZYME; ACTIVE-SITE; BINDING; INHIBITION; TYROSINE-48 AB The catalytic reduction of D-glyceraldehyde to glycerol by aldose reductase has been investigated with the combined potentials of quantum mechanics (QM) and molecular mechanics (MM) to resolve the question of whether Tyr48 or His110 serves as the proton donor during catalysis. Site directed mutagenesis studies favor Tyr48 as the proton donor while the presence of a water channel linking the N delta 1 of His110 to the bulk solvent suggests that His110 is the proton donor. Utilizing the combined potentials of QM and MM, the binding mode of substrate D-glyceraldehyde was investigated by optimizing the local geometry of Asp43, Lys77, Tyr48, His110 and NADPH at the active site of aldose reductase. Reaction pathways for the reduction of D-glyceraldehyde to glycerol were then constructed by treating both Tyr48 and His110 as proton donors. Comparison of energetics obtained from the reaction pathways suggests His110 to be the proton donor. Based on these findings, a reduction mechanism of D-glyceraldehyde to glycerol is described. (C) 1998 Elsevier Science B.V. C1 NEI, NIH, Bethesda, MD 20892 USA. NIH, Struct Biol Lab, DCRT, Bethesda, MD 20892 USA. Natl Inst Chem, Ljubljana, Slovenia. RP Lee, YS (reprint author), NEI, NIH, Bldg 10,RM 10B77, Bethesda, MD 20892 USA. NR 38 TC 41 Z9 41 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD MAR 9 PY 1998 VL 70 IS 3 BP 203 EP 216 PG 14 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA ZD310 UT WOS:000072672400003 PM 9546197 ER PT J AU DeVries, AC Taymans, SE Sundstrom, JM Pert, A AF DeVries, AC Taymans, SE Sundstrom, JM Pert, A TI Conditioned release of corticosterone by contextual stimuli associated with cocaine is mediated by corticotropin-releasing factor SO BRAIN RESEARCH LA English DT Article DE cocaine; endocrine; corticosterone; CRF; tolerance; classical; conditioning ID PITUITARY-ADRENAL AXIS; NEUROENDOCRINE RESPONSES; ADMINISTRATION SENSITIZES; BEHAVIORAL SENSITIZATION; LOCOMOTOR RESPONSE; INDUCED ELEVATION; SECRETION; RATS; AMPHETAMINE; ACQUISITION AB Elevated blood concentrations of corticosterone (CORT), an adrenal steroid associated with stress responses, is one of the endocrine correlates of cocaine treatment. Experiment 1 confirmed and extended previous findings that chronic cocaine treatment does not alter corticosteroid responses to cocaine. In Experiment 2, conditioned endocrine effects of cocaine were examined in three groups of rats after 7 consecutive days of treatment. Cocaine-induced conditioning was achieved using a simple contextual design. In group 1 (paired), rats were injected with cocaine (30 mg/kg), then immediately placed into a locomotor activity chamber for 30 min. One hour after the rats were returned to their home cages, they received an injection of saline. In group 2 (unpaired), rats were injected with saline, then immediately placed into a locomotor activity chamber for 30 min. One hour after the rats were returned to their home cages, they received an injection of cocaine (30 mg/kg). Rats in group 3 (control) received only saline injections, but otherwise were treated as animals in the other treatment groups. On the test day (Day 8), all rats were placed immediately into the locomotor apparatus for 30 min prior to collection of a blood sample. Blood CORT concentrations and locomotor activity in the paired group were significantly higher than in the unpaired and control groups. However, pretreatment of the rats in Experiment 3 with the corticotropin-releasing factor (CRF) antagonist, alpha-helical CRF9.41 (1 mu g, i.c.v.), on the test day, prior to exposure to cocaine-associated contextual cues, attenuated the subsequent conditioned increase in blood CORT concentrations. These data represent the first demonstration of classical conditioning of a steroid hormone response to stimuli associated with a psychoactive drug in rats and suggest that the effect is mediated by endogenous CRF. Because the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in modulating the actions of cocaine, it is plausible that such conditioned increases in CORT release by cocaine-associated cues may further predispose an organism to the reinforcing effects of the drug or enhance the susceptibility to drug-taking behavior. Alternatively, such conditioned effects may be related to the anxiogenic properties of cocaine. Further understanding of the conditioned effects of hormones in the development and expression of addictive behaviors may provide new insights into treatment of drug addiction. (C) 1998 Elsevier Science B.V. C1 NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP DeVries, AC (reprint author), Univ Maryland, Dept Zool, College Pk, MD 20742 USA. NR 53 TC 38 Z9 39 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 9 PY 1998 VL 786 IS 1-2 BP 39 EP 46 DI 10.1016/S0006-8993(97)01328-0 PG 8 WC Neurosciences SC Neurosciences & Neurology GA ZJ738 UT WOS:000073248000005 PM 9554945 ER PT J AU Cadet, JL Ladenheim, B Hirata, H AF Cadet, JL Ladenheim, B Hirata, H TI Effects of toxic doses of methamphetamine (METH) on dopamine D1 receptors in the mouse brain SO BRAIN RESEARCH LA English DT Article DE METH; toxicity; degeneration; p53 ID GERBILS MERIONES-UNGUICULATUS; DISMUTASE TRANSGENIC MICE; RAT SOMATOSENSORY CORTEX; PREFRONTAL CORTEX; METHYLAMPHETAMINE; NEUROTOXICITY; DEGENERATION; ATTENUATION; NEURONS AB Methamphetamine (METH) is a drug of abuse that causes marked DA depletion in the mammalian dopaminergic systems. These are characterized by marked decreases in presynaptic markers including dopamine (DA) levels and DA transporters. Very little research has been carried out to evaluate possible postsynaptic effects of this drug. In the present study, we assessed the status of METH on striatal DA D1 receptors labeled with [H-3]SCH23390 after toxic doses of METH that were shown to cause marked depletion of various markers of presynaptic DA systems in mice [J. Neurochem. 69 (1997) 780]. Our results show that these doses of METH caused 30% decrease in striatal DA D1 receptors. In contrast, p53 knockout mice that show protection against the toxic effects of METH show no significant decreases in DA D1 receptors. These results suggest that toxic doses of METH that cause loss of presynaptic DA markers might also affect postsynaptic elements. We discuss the possibility that these changes might be secondary to toxic effects of METH on intrinsic striatal cell bodies. (C) 1998 Elsevier Science B.V. C1 NIDA, Mol Neuropsychiat Sect, NIH, Intramural Res Program, Baltimore, MD 21224 USA. RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Sect, NIH, Intramural Res Program, POB 5180,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 19 TC 13 Z9 13 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 MAR 9 PY 1998 VL 786 IS 1-2 BP 240 EP 242 DI 10.1016/S0006-8993(97)01432-7 PG 3 WC Neurosciences SC Neurosciences & Neurology GA ZJ738 UT WOS:000073248000030 PM 9555035 ER PT J AU Senzaki, H Gluzband, YA Pak, PH Crow, MT Janicki, JS Kass, DA AF Senzaki, H Gluzband, YA Pak, PH Crow, MT Janicki, JS Kass, DA TI Synergistic exacerbation of diastolic stiffness from short-term tachycardia-induced cardiodepression and angiotensin II SO CIRCULATION RESEARCH LA English DT Article DE heart failure; diastole; metalloproteinase; myocardium; ventricle ID INDUCED HEART-FAILURE; LEFT-VENTRICULAR DYSFUNCTION; ALDOSTERONE SYSTEM; CONVERTING ENZYME; MYOCYTE NECROSIS; MATRIX METALLOPROTEINASES; COLLAGEN DEGRADATION; CARDIAC MYOCYTES; GENE-EXPRESSION; PRESSURE-VOLUME AB Synergistic interaction between angiotensin II (Ang II) and evolving cardiodepression may play an important role in worsening chamber function, particularly in diastole, To test this hypothesis, Ang II was infused at 10 or 17 ng.kg(-1).min(-1) in 18 conscious dogs 4 days before and during induction of subacute cardiodepression by 48-hour tachypacing. The lower dose yielded negligible systemic pressure changes. Twelve additional animals served as paced-only controls. Pressure-dimension relations were recorded, and serial endocardial biopsies were obtained to assess histological and metalloproteinase (MMP) changes. Forty-eight-hour pacing alone depressed systolic function but had little effect on diastolic stiffness. Ang II alone only modestly raised diastolic stiffness at both doses and enhanced contractility at the higher dose. These changes recovered toward baseline after a 7-day infusion, However, Ang II (at either dose) combined with 48-hour pacing markedly increased ventricular stiffness (110+/-26% over baseline) and end-diastolic pressure (22+/-1.7 mm Hg). In contrast, pacing-induced inotropic and relaxation abnormalities were not exacerbated by Ang II. Zymography revealed MMP activation (72- and 92-kD gelatinases and 52-kDa caseinase) after a 4-day Ang II infusion (at both doses), which persisted during pacing, Tachypacing initiated 24 hours after cessation of a 7-day Ang II infusion also resulted in diastolic stiffening and corresponded with MMP reactivation. Ang II also induced myocyte necrosis, inflammation, and subsequent interstitial fibrosis, but these changes correlated less with chamber mechanics. Thus, Ang II amplifies and accelerates diastolic dysfunction when combined with evolving cardiodepression, This phenomenon may also underlie Ang II influences in late-stage cardiomyopathy, when chamber distensibility declines. C1 Johns Hopkins Med Inst, Div Cardiol, Dept Med, Baltimore, MD 21287 USA. NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. Auburn Univ, Dept Physiol & Pharmacol, Auburn, AL 36849 USA. RP Kass, DA (reprint author), Johns Hopkins Med Inst, Div Cardiol, Dept Med, 600 N Wolfe St, Baltimore, MD 21287 USA. EM dkass@eureka.wbrne.jhu.edu OI Senzaki, Hideaki/0000-0002-8289-0953 FU NHLBI NIH HHS [HL P50 52307, HL-47511] NR 50 TC 28 Z9 28 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD MAR 9 PY 1998 VL 82 IS 4 BP 503 EP 512 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA ZC358 UT WOS:000072569900012 PM 9506711 ER PT J AU Wan, RQ Noguera, EC Weiss, SRB AF Wan, RQ Noguera, EC Weiss, SRB TI Anticonvulsant effects of intra-hippocampal injection of TRH in amygdala kindled rats SO NEUROREPORT LA English DT Article DE anticonvulsant; epilepsy; hippocampus; kindling; TRH ID THYROTROPIN-RELEASING-HORMONE; BENZODIAZEPINE RECEPTOR LIGANDS; DIFFERENT SEIZURE MODELS; MESSENGER-RNA; WITHDRAWAL CHARACTERISTICS; CONTINGENT TOLERANCE; LIMBIC STRUCTURES; MECHANISMS; EPILEPSY; CARBAMAZEPINE AB THE anticonvulsant effects of intra-hippocampal thyrotropin-release hormone (TRH) were examined in amygdala kindled rats. Subjects were implanted unilaterally with an electrode in the amygdala and bilaterally with guide cannulae in the hippocampus, aimed at the dorsal and ventral dentate gyri. Rats were kindled daily with suprathreshold electrical stimulation (800 mu A, 1 ms pulse width, 100 Hz, duration 0.5 s) until seizures were reliably elicited. The afterdischarge (AD) duration, seizure duration, and seizure stage were recorded daily, and AD thresholds were determined after kindling was completed. TRH was infused into each of the four cannulae of freely moving rats at doses of 0 (vehicle), 1.25, 2.5 and 5 mu g/site. Five minutes after the last infusion, the rats received electrical stimulation at their AD threshold (mean = 135 mu A) + 50 mu A. TRH reduced the AD and seizure duration in a dose-dependent manner. At the dose of 2.5 mu g/site, TRH also reduced AD and seizure duration in rats stimulated with suprathreshold current (800 mu A). However, TRH had minimal effects on seizure stage irrespective of the stimulation intensity. These results suggest that the seizure-induced elevations of TRH in the hippocampus, as demonstrated in previous studies, may be part of an endogenous anticonvulsant compensatory mechanism and that further elevations of TRH in the hippocampus can produce anticonvulsant effects mainly by reducing the AD and seizure duration. C1 NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. RP Wan, RQ (reprint author), NIMH, Biol Psychiat Branch, Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 36 TC 26 Z9 26 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAR 9 PY 1998 VL 9 IS 4 BP 677 EP 682 DI 10.1097/00001756-199803090-00021 PG 6 WC Neurosciences SC Neurosciences & Neurology GA ZC115 UT WOS:000072541400022 PM 9559937 ER PT J AU Finberg, JPM Takeshima, T Johnston, JM Commissiong, JW AF Finberg, JPM Takeshima, T Johnston, JM Commissiong, JW TI Increased survival of dopaminergic neurons by rasagiline, a monoamine oxidase B inhibitor SO NEUROREPORT LA English DT Article DE dopaminergic neurons; GABAergic neurons; microisland cultures; neurodegenerative diseases; neuronal survival; Parkinson's disease; tissue culture ID PARKINSONS-DISEASE; FACIAL MOTONEURONS; SERUM DEPRIVATION; RAT; DEPRENYL; ASTROCYTES; THERAPY; CULTURE; RESCUE; BRAIN AB BOTH deprenyl and rasagiline (R(+)-N-propargyl-1-aminoindane mesylate), at a concentration of 1-10 mu M, increased survival in vitro of rat E14 mesencephalic dopaminergic neurons that had been primed with 10% serum for 12 h (p < 0.05). Rasagiline, but not deprenyl, also increased total neuronal (MAP2-positive) survival (p < 0.05) Under serum-free conditions, rasagiline, but not deprenyl, retained its neuroprotective action on dopaminergic neurones. GABAergic neurons were not affected by either deprenyl or rasagiline. Clorgyline, an MAO-A inhibitor, did not exert any of these effects. The protective action of rasagiline on dopaminergic neurons, even under stringent serum-free conditions, is striking, and warrants further investigation for a role in the treatment of Parkinson's disease. C1 Technion Israel Inst Technol, Fac Med, Dept Pharmacol, Haifa, Israel. LMNC, NINDS, Neural Transplantat Unit, NIH, Bethesda, MD 20892 USA. LMB, NINDS, NIH, Bethesda, MD 20892 USA. RP Finberg, JPM (reprint author), Technion Israel Inst Technol, Fac Med, Dept Pharmacol, POB 9649, Haifa, Israel. NR 23 TC 82 Z9 83 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAR 9 PY 1998 VL 9 IS 4 BP 703 EP 707 PG 5 WC Neurosciences SC Neurosciences & Neurology GA ZC115 UT WOS:000072541400027 PM 9559942 ER PT J AU Bluming, AZ AF Bluming, AZ TI Avrum Zvi Bluming SO LANCET LA English DT Editorial Material C1 Lymphoma Treatment Ctr, Kampala, Uganda. NCI, Bethesda, MD 20892 USA. Amer Coll Phys, Philadelphia, PA 19106 USA. RP Bluming, AZ (reprint author), Lymphoma Treatment Ctr, Kampala, Uganda. NR 4 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAR 7 PY 1998 VL 351 IS 9104 BP 764 EP 764 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA ZB359 UT WOS:000072463800072 ER PT J AU Igishi, T Gutkind, JS AF Igishi, T Gutkind, JS TI Tyrosine kinases of the Src family participate in signaling to MAP kinase from both G(q), and G(i)-coupled receptors SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROTEIN-COUPLED RECEPTORS; BETA-GAMMA-SUBUNITS; C-SRC; ACTIVATION; PATHWAY; PHOSPHORYLATION; PYK2; RAS; FIBROBLASTS AB Src-related kinases have been recently implicated in signaling from G(i)-coupled receptors to MAP kinase. Whether Src-like kinases participate in MAP kinase activation by the large family of receptors coupled to G proteins of the G(q) family is still unclear. Here, we show that a specific inhibitor for Src-like kinases, 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP1), and dominant negative mutants of Src suppress MAP kinase activation in COS-7 cells when elicited by either m1 and m2 muscarinic receptors, which are typical G(q) and G(i)-coupled receptors, respectively. Furthermore, activation of MAP kinase by overexpression of beta gamma subunits, but not by stimulation with phorbol esters was also inhibited by the dominant-negative Src. In contrast, a dominant negative Pyk2 had only mild effects on m1 and m2 mediated-MAP kinase activation. We concluded that Src like kinase(s), acting downstream from beta gamma dimers, play an important role relaying signals from both G(q), and G(i)-coupled receptors to MAP kinase. (C) 1998 Academic Press. C1 NIDR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Gutkind, JS (reprint author), NIDR, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Bldg 30,Room 212, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009 NR 28 TC 61 Z9 62 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 6 PY 1998 VL 244 IS 1 BP 5 EP 10 DI 10.1006/bbrc.1998.8208 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZB929 UT WOS:000072522500002 PM 9514877 ER PT J AU Moore-Hoon, ML Turner, RJ AF Moore-Hoon, ML Turner, RJ TI Increased expression of the secretory Na+-K+-2Cl(-)cotransporter with differentiation of a human intestinal cell line SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE HT-29 cells; salt and water secretion; epithelial differentiation ID COTRANSPORTER; TRANSPORT; BUTYRATE; GROWTH; CLONES; HT29; RNA AB We studied the expression of the secretory Na+-K+ 2Cl(-) cotransporter during epithelial differentiation using the clonal human adenocarcinoma cell line HT29-18. Differentiation of HT29-18 cells was accompanied by up to 7-fold increases in cotransporter protein levels, similar to 3-fold increases in cotransporter mRNA levels, and similar to 2.5-fold increases in cotransporter functional expression, No apparent change in cotransporter mRNA stability was observed with differentiation, suggesting that these effects may be due to differences in mRNA transcription rate. Confocal immunofluorescence microscopy showed that undifferentiated cells grew in multilayers and exhibited a diffuse, apparently unlocalized membrane labeling by anti-Na+-K+-2Cl(-) cotransporter antibody. In contrast, differentiated cells grew in monolayers with strong cotransporter labeling localized to the basal and lateral membranes. Taken together with previous studies demonstrating that expression of the cystic fibrosis transmembrane regulator is also increased following HT29-18 cell differentiation, our results suggest that these cells provide a promising model for studying epithelial differentiation to a Cl- secretory phenotype. (C) 1998 Academic Press. C1 NIDR, Membrane Biol Sect, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Moore-Hoon, ML (reprint author), NIDR, Membrane Biol Sect, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. NR 18 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 6 PY 1998 VL 244 IS 1 BP 15 EP 19 DI 10.1006/bbrc.1998.8206 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZB929 UT WOS:000072522500004 PM 9514875 ER PT J AU Shindo, M Nakano, H Kuroyanagi, H Shirasawa, T Mihara, M Gilbert, DJ Jenkins, NA Copeland, NG Yagita, H Okumura, K AF Shindo, M Nakano, H Kuroyanagi, H Shirasawa, T Mihara, M Gilbert, DJ Jenkins, NA Copeland, NG Yagita, H Okumura, K TI cDNA cloning, expression, subcellular localization, and chromosomal assignment of mammalian aurora homologues, aurora-related kinase (ARK) 1 and 2 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROTEIN-KINASE; DROSOPHILA POLO; DOWN-REGULATION; MOUSE; GENE; MITOSIS; CENTROSOME; INDUCTION; EXTRACTS; SPINDLE AB Chromosomal segregation during mitosis as well as meiosis is considered to be regulated by multiple kinases, but the precise mechanism remains largely unknown. A mutation in Drosophila, designated aurora, was identified as a responsible gene for a chromosomal segregation defect and encodes a putative serine-threonine kinase. Here we have identified mammalian aurora homologues, designated aurora-related kinase (ARK) 1 and ARK2. Kinase domains of murine ARK1 and ARK2 showed 61 and 62% identity, respectively, to that of aurora at the amino acid levels, respectively. Cell cycle analysis revealed that the expression of ARK1 was correlated with G2/M phase, while ARK2 was expressed during S and G2/M phases. Immunofluorescence analysis demonstrated that ARK2 was mainly localized to the midbody, while ARK1 has been reported to be localized to the spindle pole during mitosis. Collectively, these results suggest that these two kinases may have distinct roles with different expression timing and subcellular localization during the cell cycle progression. Interspecific backcross mapping revealed that Ark1 is located in a distal region of mouse chromosome 2, while Ark2 is located in a central region of mouse chromosome 11. (C) 1998 Academic Press. C1 Juntendo Univ, Sch Med, Dept Immunol, Bunkyo Ku, Tokyo 113, Japan. Tokyo Metropolitan Inst Gerontol, Dept Neurophysiol, Itabashi Ku, Tokyo 173, Japan. Tottori Univ, Fac Med, Dept Dermatol, Tottori 683, Japan. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Okumura, K (reprint author), Juntendo Univ, Sch Med, Dept Immunol, Bunkyo Ku, 2-1-1 Hongo, Tokyo 113, Japan. OI Nakano, Hiroyasu/0000-0003-4843-1427 NR 36 TC 69 Z9 77 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 6 PY 1998 VL 244 IS 1 BP 285 EP 292 DI 10.1006/bbrc.1998.8250 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZB929 UT WOS:000072522500053 PM 9514916 ER PT J AU Yan, SZ Rodrigues, RG Cahn-Hidalgo, D Walsh, TJ Roberts, DD AF Yan, SZ Rodrigues, RG Cahn-Hidalgo, D Walsh, TJ Roberts, DD TI Hemoglobin induces binding of several extracellular matrix proteins to Candida albicans - Identification of a common receptor for fibronectin, fibrinogen, and laminin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-SURFACE; STAPHYLOCOCCUS-AUREUS; THROMBOSPONDIN; ADHERENCE; ADHESION; PATHOGENESIS; SPECIFICITY; SEQUENCES; SYSTEMS; LIGAND AB Host infection by the pathogenic fungus Candida albicans is initiated by adhesion and mediated by binding to several host extracellular matrix proteins. Previously, we demonstrated that hemoglobin supplemented into a chemically defined medium significantly and specifically induced fibronectin binding to C. albicans. We now report that hemoglobin also induces binding of laminin, fibrinogen, and type IV collagen but not of thrombospondin-1 or type I collagen. The binding of each protein was inhibited by the respective unlabelled ligand in a concentration-dependent manner. Fibrinogen inhibited the binding of radiolabeled fibronectin,, laminin, and fibrinogen with similar IC50 values, suggesting that a single promiscuous, receptor recognizes these three proteins, Competitive binding studies indicated that a second class of receptor binds specifically to laminin. Growth of C. albicans in the presence of hemoglobin also increased cell adhesion to immobilized fibronectin, laminin, fibrinogen, and type IV collagen but not to thrombospondin-1 or type I collagen. Exposure to hemoglobin induced increased or de novo expression of several surface proteins on C. albicans. One of these proteins with a molecular weight of 55,000 recognized fibronectin, based an ligand protection and affinity chromatography an immobilized fibronectin. Thus, hemoglobin induces both promiscuous and specific receptors for extracellular matrix proteins and, therefore, may regulate matrix adhesion during dissemination of C. albicans infections. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Pediat Branch, NIH, Bethesda, MD 20892 USA. RP Roberts, DD (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Rm 2A33,10 Ctr Dr MSC 1500, Bethesda, MD 20892 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 40 TC 32 Z9 32 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 6 PY 1998 VL 273 IS 10 BP 5638 EP 5644 DI 10.1074/jbc.273.10.5638 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZA256 UT WOS:000072345000036 PM 9488693 ER PT J AU Aoyama, T Peters, JM Iritani, N Nakajima, T Furihata, K Hashimoto, T Gonzalez, FJ AF Aoyama, T Peters, JM Iritani, N Nakajima, T Furihata, K Hashimoto, T Gonzalez, FJ TI Altered constitutive expression of fatty acid-metabolizing enzymes in mice lacking the peroxisome proliferator-activated receptor alpha (PPAR alpha) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RAT-LIVER MITOCHONDRIA; ACYL-COENZYME-A; BETA-OXIDATION ENZYMES; LONG-CHAIN; MOLECULAR-CLONING; GENE-EXPRESSION; 3-HYDROXYACYL-COA DEHYDROGENASE; TRANSCRIPTIONAL REGULATION; NUCLEOTIDE-SEQUENCE; OMEGA-HYDROXYLASE AB Peroxisome proliferative-activated receptor alpha (PPAR alpha) is a member of the steroid/nuclear receptor superfamily and mediates the biological and toxicological effects of peroxisome proliferators. To determine the physiological role of PPAR alpha in fatty acid metabolism, levels of peroxisomal and mitochondrial fatty acid metabolizing enzymes were determined in the PPAR alpha null mouse, Constitutive liver beta-oxidation of the long chain fatty acid, palmitic acid, was lower in the PPAR alpha null mice as compared with wild type mice, indicating defective mitochondrial fatty acid catabolism. In contrast, constitutive oxidation of the very long chain fatty acid, lignoceric acid, was not different between wild type and PPAR alpha null mice, suggesting that constitutive expression of enzymes involved in peroxisomal beta-oxidation is independent of PPAR alpha. Indeed, the PPAR alpha null mice had normal levels of the peroxisomal acyl-CoA oxidase, bifunctional protein (hydratase + 3-hydroxyacyl-CoA dehydrogenase), and thiolase but lower constitutive expression of the D-type bifunctional protein (hydratase + 3-hydroxyacyl-CoA dehydrogenase), Several mitochondrial fatty acid metabolizing enzymes including very long chain acyl-CoA dehydrogenase, long chain acyl-CoA dehydrogenase, short chain-specific 3-ketoacyl-CoA thiolase, and long chain acyl-CoA synthetase are also expressed at lower levels in the untreated PPAR alpha null mice, whereas other fatty acid metabolizing enzymes were not different between the untreated null mice and wild type mice. A lower constitutive expression of mRNAs encoding these enzymes was also found, suggesting that the effect was due to altered gene expression. In wild type mice, both peroxisomal and mitochondrial enzymes were induced by the peroxisome proliferator Wy-14,643; induction was not observed in the PPAR alpha null animals, These data indicate that PPAR alpha modulates constitutive expression of genes encoding several mitochondrial fatty acid-catabolizing enzymes in addition to mediating inducible mitochondrial and peroxisomal fatty acid beta-oxidation, thus establishing a role for the receptor in fatty acid homeostasis. C1 Shinshu Univ, Sch Med, Dept Biochem, Asahi Ku, Nagano 390, Japan. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. Tezukayama Gakuin Coll, Osaka 590, Japan. Shinshu Univ, Sch Med, Dept Hyg & Med Genet, Nagano 390, Japan. Shinshu Univ, Sch Med, Dept Lab Med, Nagano 390, Japan. RP Aoyama, T (reprint author), Shinshu Univ, Sch Med, Dept Biochem, Asahi Ku, Nagano 390, Japan. EM toshifu@gipac.shinshu-u.ac.jp RI Peters, Jeffrey/D-8847-2011 NR 63 TC 588 Z9 606 U1 2 U2 17 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 6 PY 1998 VL 273 IS 10 BP 5678 EP 5684 DI 10.1074/jbc.273.10.5678 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZA256 UT WOS:000072345000041 PM 9488698 ER PT J AU Arispe, N Ma, JJ Jacobson, KA Pollard, HB AF Arispe, N Ma, JJ Jacobson, KA Pollard, HB TI Direct activation of cystic fibrosis transmembrane conductance regulator channels by 8-cyclopentyl-1,3-dipropylxanthine (CPX) and 1,3-diallyl-8-cyclohexylxanthine (DAX) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; CHLORIDE CHANNEL; ADENOSINE RECEPTORS; IDENTIFICATION; DELTA-F508; GENE; MUTATION; EFFLUX; CELLS; DOMAIN AB 8-Cyclopentyl-1,3-dipropylxanthine (CPX) and 1,3-diallyl-8-cyclohexylxanthine (DAX) are xanthine adenosine antagonists which activate chloride efflux from cells expressing either wild-type or mutant (Delta F508) cystic fibrosis transmembrane conductance regulator (CFTR). These drugs are active in extremely low concentrations, suggesting their possible therapeutic uses in treating cystic fibrosis. However, knowledge of the mechanism of action of these compounds is lacking. We report here that the same low concentrations of both CPX and DAX which activate chloride currents from cells also generate a profound activation of CFTR channels incorporated into planar lipid bilayers. The process of activation involves a pronounced increase in the total conductive time of the incorporated CFTR channels. The mechanism involves an increase in the frequency and duration of channel opening events. Thus, activation by these drugs of chloride efflux in cells very likely involves direct interaction of the drugs with the CFTR protein. We anticipate that this new information will contribute fundamentally to the rational development of these and related compounds for cystic fibrosis therapy. C1 Uniformed Serv Univ Hlth Sci, Inst Mol Med, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Dept Anat & Cell Biol, Bethesda, MD 20814 USA. Case Western Reserve Univ, Dept Physiol & Biophys, Cleveland, OH 44106 USA. NIDDK, Bioorgan Chem Sect, Chem Lab, NIH, Bethesda, MD 20892 USA. RP Arispe, N (reprint author), Uniformed Serv Univ Hlth Sci, Inst Mol Med, Bethesda, MD 20814 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031127-01, Z99 DK999999] NR 39 TC 48 Z9 48 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 6 PY 1998 VL 273 IS 10 BP 5727 EP 5734 DI 10.1074/jbc.273.10.5727 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZA256 UT WOS:000072345000048 PM 9488705 ER PT J AU Kalman, K Nguyen, A Tseng-Crank, J Dukes, ID Chandy, G Hustad, CM Copeland, NG Jenkins, NA Mohrenweiser, H Brandriff, B Cahalan, M Gutman, GA Chandy, KG AF Kalman, K Nguyen, A Tseng-Crank, J Dukes, ID Chandy, G Hustad, CM Copeland, NG Jenkins, NA Mohrenweiser, H Brandriff, B Cahalan, M Gutman, GA Chandy, KG TI Genomic organization, chromosomal localization, tissue distribution, and biophysical characterization of a novel mammalian Shaker-related voltage-gated potassium channel, Kv1.7 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PANCREATIC BETA-CELLS; GENETIC-LINKAGE MAP; K+ CHANNELS; FUNCTIONAL EXPRESSION; NUCLEOTIDE-SEQUENCE; LEPTIN RECEPTOR; DROSOPHILA; ENCODES; FAMILY; MUSCLE AB We report the isolation of a novel mouse voltage-gated Shaker-related K+ channel gene, Kv1.7 (Kcna7/KCNA7). Unlike other known Kv1 family genes that have intronless coding regions, the protein-coding region of Ku1.7 is interrupted by a 1,9-kilobase pair intron, The Kv1.7 gene and the related Kv3.3 (Kcnc3/KCNC3) gene map to mouse chromosome 7 and human chromosome 19q13.3, a region that has been suggested to contain a diabetic susceptibility locus, The mouse Kv1,7 channel is voltage-dependent and rapidly inactivating, exhibits cumulative inactivation, and has a single channel conductance of 21 pS, It is potently blocked by noxiustoxin and stichodactylatoxin, and is insensitive to tetraethylammonium, kaliotoxin, and charybdotoxin. Northern blot analysis reveals similar to 3-kilobase pair Kv1.7 transcripts in mouse heart and skeletal muscle, In situ hybridization demonstrates the presence of Kv1.7 in mouse pancreatic islet cells. Kv1.7 was also isolated from mouse brain and hamster insulinoma cells by polymerase chain reaction. C1 Univ Calif Irvine, Sch Med, Dept Physiol & Biophys, Irvine, CA 92697 USA. Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92697 USA. Glaxo Wellcome Res Inst, Res Triangle Pk, NC 27709 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. Univ Calif Lawrence Livermore Natl Lab, Ctr Human Genome, Livermore, CA 94550 USA. RP Chandy, KG (reprint author), Univ Calif Irvine, Sch Med, Dept Physiol & Biophys, Rm 291,Joan Irvine Simth Hall, Irvine, CA 92697 USA. EM gchandy@uci.edu FU NIAID NIH HHS [AI-24783]; NIGMS NIH HHS [GMOD54872]; NINDS NIH HHS [NS14609] NR 37 TC 53 Z9 54 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 6 PY 1998 VL 273 IS 10 BP 5851 EP 5857 DI 10.1074/jbc.273.10.5851 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZA256 UT WOS:000072345000065 PM 9488722 ER PT J AU Rogakou, EP Pilch, DR Orr, AH Ivanova, VS Bonner, WM AF Rogakou, EP Pilch, DR Orr, AH Ivanova, VS Bonner, WM TI DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CALCIUM-DEPENDENT PHOSPHORYLATION; ACTIVATED PROTEIN-KINASE; TREATED HELA-CELLS; ACETYLATION; GENE; CHROMATIN; SEQUENCE; NUCLEI; DAMAGE; MOUSE AB When mammalian cell cultures or mice are exposed to ionizing radiation in survivable or lethal amounts, novel mass components are found in the histone H2A region of two-dimensional gels, Collectively referred to as gamma, these components are formed in vivo by several procedures that introduce double-stranded breaks into DNA. gamma-Components, which appeared to be the only major novel components detected by mass or (PO4)-P-32 incorporation on acetic acid-urea-Triton X-100-acetic acid-urea-cetyltrimethylammonium bromide or SDS-acetic. acidurea-cetyltrimethylammonium bromide gels after exposure of cells to ionizing radiation, are shown to be histone H2AX species that have been phosphorylated specifically at serine 139. gamma-H2AX appears rapidly after exposure of cell, cultures to ionizing radiation; half-maximal amounts are reached by I min and maximal amounts by 10 min, At the maximum, approximately 1% of the H2AX becomes gamma-phosphorylated per gray of ionizing radiation, a finding that indicates that 35 DNA double-stranded breaks, the number introduced by each gray into the 6 x 10(9) base pairs of a mammalian G(1) genome, leads to the gamma-phosphorylation of H2AX distributed over 1% of the chromatin, Thus, about 0.03% of the chromatin appears to be involved per DNA double-stranded break, This value, which corresponds to about 2 x 10(6) base pairs of DNA per double-stranded break, indicates that large amounts of chromatin are involved with each DNA double-stranded break, Thus, gamma-H2AX formation is a rapid and sensitive cellular response to the presence of DNA double-stranded breaks, a response that may provide insight into higher order chromatid structures. C1 NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Bonner, WM (reprint author), NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bldg 37,Rm 5D17, Bethesda, MD 20892 USA. NR 44 TC 2777 Z9 2860 U1 18 U2 130 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 6 PY 1998 VL 273 IS 10 BP 5858 EP 5868 DI 10.1074/jbc.273.10.5858 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZA256 UT WOS:000072345000066 PM 9488723 ER PT J AU Kalebic, T AF Kalebic, T TI HIV vaccine trials SO SCIENCE LA English DT Letter C1 NCI, Bethesda, MD 20892 USA. RP Kalebic, T (reprint author), NCI, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAR 6 PY 1998 VL 279 IS 5356 BP 1434 EP 1435 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZA527 UT WOS:000072372900006 PM 9508712 ER PT J AU Nash, HA AF Nash, HA TI Protein structure - Topological nuts and bolts SO SCIENCE LA English DT Article ID DNA TOPOISOMERASES C1 NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Nash, HA (reprint author), NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 11 TC 4 Z9 4 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAR 6 PY 1998 VL 279 IS 5356 BP 1490 EP 1491 DI 10.1126/science.279.5356.1490 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZA527 UT WOS:000072372900054 PM 9508726 ER PT J AU Joyce, S Woods, AS Yewdell, JW Bennink, JR De Silva, AD Boesteanu, A Balk, SP Cotter, RJ Brutkiewicz, RR AF Joyce, S Woods, AS Yewdell, JW Bennink, JR De Silva, AD Boesteanu, A Balk, SP Cotter, RJ Brutkiewicz, RR TI Natural ligand of mouse CD1d1: Cellular glycosylphosphatidylinositol SO SCIENCE LA English DT Article ID FAST ATOM BOMBARDMENT; T-CELLS; MASS-SPECTROMETRY; PEPTIDES; FAMILY AB Mouse CD1d1, a member of the CD1 family of evolutionarily conserved major histocompatibility antigen-like molecules, controls the differentiation and function of a T lymphocyte subset, NK1(+) natural T cells, proposed to regulate immune responses. The CD1d1 crystal structure revealed a large hydrophobic binding site occupied by a ligand of unknown chemical nature. Mass spectrometry and metabolic radiolabeling were used to identify cellular glycosylphosphatidylinositol as a major natural ligand of CD1d1. CD1d1 bound glycosylphosphatidylinositol through its phosphatidylinositol aspect with high affinity. Glycosylphosphatidylinositol or another glycolipid could be a candidate natural ligand for CD1d1-restricted T cells. C1 Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Microbiol & Immunol, Hershey, PA 17033 USA. Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. RP Joyce, S (reprint author), Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Microbiol & Immunol, Hershey, PA 17033 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 27 TC 335 Z9 342 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAR 6 PY 1998 VL 279 IS 5356 BP 1541 EP 1544 DI 10.1126/science.279.5356.1541 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZA527 UT WOS:000072372900066 PM 9488653 ER PT J AU Cutler, JA AF Cutler, JA TI Calcium-channel blockers for hypertension - Uncertainty continues SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MYOCARDIAL-INFARCTION; TRIAL; MORTALITY C1 NHLBI, Bethesda, MD 20892 USA. RP Cutler, JA (reprint author), NHLBI, Bethesda, MD 20892 USA. NR 15 TC 61 Z9 62 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 5 PY 1998 VL 338 IS 10 BP 679 EP 681 DI 10.1056/NEJM199803053381009 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA YZ844 UT WOS:000072299700009 PM 9486999 ER PT J AU Bonvini, P Nguyen, P Trepel, J Neckers, LM AF Bonvini, P Nguyen, P Trepel, J Neckers, LM TI In vivo degradation of N-myc in neuroblastoma cells is mediated by the 26S proteasome SO ONCOGENE LA English DT Article DE N-myc; ubiquitin; proteasome ID MULTICATALYTIC PROTEINASE COMPLEX; NUCLEAR PROTEINS; NEURO-BLASTOMA; M-CALPAIN; ORNITHINE DECARBOXYLASE; SELECTIVE INHIBITORS; PROTEOLYTIC SYSTEM; KAPPA-B; UBIQUITIN; AMPLIFICATION AB N-myc is a short-lived transcription factor, frequently amplified in human neuroblastomas. The ubiquitin-proteasome system is involved in the degradation of many short-lived cellular proteins and previous studies have shown that ubiquitin-dependent proteolysis is implicated in the turn-over of N-myc in vitro. However, calpain has also been implicated in N-myc degradation in vitro. Here we report that, in vivo, N-myc is a sensitive substrate for the 26S proteasome in N-myc amplified neuroblastoma cells. We observed that inhibition of the 26S proteasome with two inhibitors, ALLnL and lactacystin, led to an elevation of the N-myc protein steady-state and increased N-myc protein polyubiquitination, as revealed by ubiquitin Western blotting. Pulse-chase experiments have shown that the increased N-myc levels resulted from stabilization of the protein. In contrast treatment with several calpain and cathepsin inhibitors failed to block N-myc degradation in vivo. Furthermore, fluorescence microscopy of ALLnL-treated cells localized N-myc exclusively to the nuclear compartment, suggesting the absence of a requirement for transport to the cytoplasm prior to degradation. C1 NCI, Dept Cell & Canc Biol, Med Branch, NIH, Bethesda, MD 20892 USA. RP Bonvini, P (reprint author), NCI, Dept Cell & Canc Biol, Med Branch, NIH, Bethesda, MD 20892 USA. NR 62 TC 34 Z9 34 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 5 PY 1998 VL 16 IS 9 BP 1131 EP 1139 DI 10.1038/sj.onc.1201625 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA ZA170 UT WOS:000072336000004 PM 9528855 ER PT J AU Zhang, J Kovac, P AF Zhang, J Kovac, P TI N-(2,2,-dimethoxyethyl)-, N-(2,2-diethoxyethyl)- and N-(4,4-diethoxybutyl)-6-hydroxy hexanamides as new linking agents for carbohydrates and proteins SO TETRAHEDRON LETTERS LA English DT Article ID METHYL ALPHA-GLYCOSIDE; VIBRIO-CHOLERAE O/1; O-SPECIFIC ANTIGEN; REDUCTIVE AMINATION; REPEATING UNIT; CRYSTAL-STRUCTURE; SEROTYPE-OGAWA; POLYSACCHARIDE; OLIGOSACCHARIDES; TRISACCHARIDE AB The title compounds have been conveniently synthesized by the addition reaction of epsilon-caprolactone and the corresponding readily available omega-aminoalkyl dialkyl acetals. The free aldehydes, formed from sugar glycosides bearing the described hexanamides as as aglycons, can be readily linked to proteins by reductive amination to give neoglycoconjugates. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NIDDK, NIH, Bethesda, MD 20892 USA. RP Zhang, J (reprint author), NIDDK, NIH, 8 Ctr Dr, Bethesda, MD 20892 USA. NR 18 TC 2 Z9 2 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD MAR 5 PY 1998 VL 39 IS 10 BP 1091 EP 1094 DI 10.1016/S0040-4039(97)10787-0 PG 4 WC Chemistry, Organic SC Chemistry GA YW980 UT WOS:000071994100003 ER PT J AU Miaskiewicz, K Smith, DA AF Miaskiewicz, K Smith, DA TI Epoxidation by dimethyldioxirane: Effects of intramolecular and intermolecular interactions SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID TRANSITION-STATE; CHEMISTRY; DIOXIRANES; SOLVENT; OXIDATION AB The Density Functional Theory B3LYP/6-31G* method is used to provide a detailed understanding of the origins of infra-and intermolecular (solvent) effects on the epoxidation of C-C double bonds by dimethyldioxirane (DMDO) in a model system, 2-methyl-2-butene. We found that the presence of hydrogen bond donor substituents, such as hydroxyl and amino groups, at the allylic position on the olefin leads to substantially decreased activation barriers for epoxidation. This effect is observed exclusively when a hydrogen bond interaction is present between the hydroxyl or amino substituent and the attacking DMDO molecule, and is not caused by inductive electronic effects of the substituents. An even more significant lowering of the activation barrier is seen when DMDO forms a hydrogen bond with methanol (representing a hydrogen bond donor solvent) in the transition state. Solvent polarity, studied using the SCIPCM model, influences the epoxidation barrier to a much smaller degree than do hydrogen bonding interactions. C1 DASGrp Inc, Johnstown, PA 15905 USA. RP Miaskiewicz, K (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC, POB B,Bldg 430, Frederick, MD 21702 USA. NR 20 TC 22 Z9 22 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAR 4 PY 1998 VL 120 IS 8 BP 1872 EP 1875 DI 10.1021/ja972800o PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA ZA491 UT WOS:000072368600028 ER PT J AU Yarchoan, R Jaffe, ES Little, R AF Yarchoan, R Jaffe, ES Little, R TI Diagnosing central nervous system lymphoma in the setting of AIDS: a step forward SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID EPSTEIN-BARR-VIRUS; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; NON-HODGKINS-LYMPHOMA; CEREBROSPINAL-FLUID; KAPOSIS-SARCOMA; DNA-SEQUENCES C1 NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. NCI, Div Clin Sci, Pathol Lab, Bethesda, MD 20892 USA. RP Yarchoan, R (reprint author), NIH, Bldg 10,Rm 12N226, Bethesda, MD 20892 USA. EM yarchoan@helix.nih.gov NR 17 TC 9 Z9 9 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 4 PY 1998 VL 90 IS 5 BP 346 EP 347 DI 10.1093/jnci/90.5.346 PG 2 WC Oncology SC Oncology GA ZA064 UT WOS:000072325300002 PM 9498478 ER PT J AU Vortmeyer, AO Boni, R Pak, E Pack, S Zhuang, ZP AF Vortmeyer, AO Boni, R Pak, E Pack, S Zhuang, ZP TI Multiple endocrine neoplasia 1 gene alterations in MEN1-associated and sporadic lipomas SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI, Pathol Lab, Div Clin Sci, Bethesda, MD 20892 USA. Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. RP Zhuang, ZP (reprint author), NIH, Bldg 10,Rm 2N212, Bethesda, MD 20892 USA. RI Pack, Svetlana/C-2020-2014 NR 7 TC 27 Z9 27 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 4 PY 1998 VL 90 IS 5 BP 398 EP 399 DI 10.1093/jnci/90.5.398 PG 2 WC Oncology SC Oncology GA ZA064 UT WOS:000072325300014 PM 9498491 ER PT J AU Olsen, V Guruprasad, K Cawley, NX Chen, HC Blundell, TL Loh, YP AF Olsen, V Guruprasad, K Cawley, NX Chen, HC Blundell, TL Loh, YP TI Cleavage efficiency of the novel aspartic protease yapsin 1 (Yap3p) enhanced for substrates with arginine residues flanking the P1 site: Correlation with electronegative active-site pockets predicted by molecular modeling SO BIOCHEMISTRY LA English DT Article ID OPIOMELANOCORTIN-CONVERTING ENZYME; KEX2-LIKE PROCESSING ENDOPROTEASE; PROPROTEIN CONVERTASE; DATA-BANK; HOMOLOGOUS PROTEINS; CDNA STRUCTURE; YEAST KEX2; IDENTIFICATION; GENE; RAT AB Yapsin 1, a novel aspartic protease with unique specificity for basic residues, was shown to cleave CCK13-33 at Lys(23). Molecular modeling of yapsin 1 identified the active-site cleft to have negative residues close to or within the S6, S3, S2, S1, S1', S2', and S3' pockets and is more electronegative than rhizopuspepsin or endothiapepsin. In particular, the S2' subsite has three negative charges in and close to this pocket that can provide strong electrostatic interactions with a basic residue. The model, therefore, predicts that substrates with a basic residue in the P1 position would be favored with additional basic residues binding to the other electronegative pockets. A deletion of six residues close to the S1 pocket in yapsin 1, relative to rhizopuspepsin and other aspartic proteases of known 3D structure, is likely to affect its specificity. The model was tested using CCK13-33 analogues. We report that yapsin 1 preferentially cleaves a CCK13-33 substrate with a basic residue in the pi position since the substrates with Ala in pi were not cleaved. Furthermore, the cleavage efficiency of yapsin 1 was enhanced for CCK13-33 analogues with arginine residues flanking the P1 position. An alanine residue, substituting for the arginine residue in the P6 position in CCK13-33, resulted in a 50% reduction in the cleavage efficiency. Substitution with arginine residues downstream of the cleavage site at the P2', P3', or P6' position increased the cleavage efficiency by 21-, 3- and 7-fold, respectively. Substitution of Lys(23) in CCK13-33 With arginine resulted not only in cleavage after the substituted arginine residue, but also forced a cleavage after Met(25), suggesting that an arginine residue in the S2' pocket is so favorable that it can affect the primary specificity of yapsin 1. These results are consistent with the predictions from the molecular model of yapsin 1. C1 NICHHD, Cellular Neurobiol Sect, Dev Neurobiol Lab, Endocrinol & Reprod Res Branch,NIH, Bethesda, MD 20892 USA. Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England. RP Loh, YP (reprint author), NICHHD, Cellular Neurobiol Sect, Dev Neurobiol Lab, Endocrinol & Reprod Res Branch,NIH, Bldg 49,Rm 5A38, Bethesda, MD 20892 USA. NR 47 TC 20 Z9 21 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 3 PY 1998 VL 37 IS 9 BP 2768 EP 2777 DI 10.1021/bi9724826 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZB940 UT WOS:000072523600007 PM 9485427 ER PT J AU Rowlett, R Yang, LH Ahmed, SA McPhie, P Jhee, KH Miles, EW AF Rowlett, R Yang, LH Ahmed, SA McPhie, P Jhee, KH Miles, EW TI Mutations in the contact region between the alpha and beta subunits of tryptophan synthase alter subunit interaction and intersubunit communication SO BIOCHEMISTRY LA English DT Article ID SALMONELLA-TYPHIMURIUM; ESCHERICHIA-COLI; ALPHA(2)BETA(2) COMPLEX; 3-DIMENSIONAL STRUCTURE; MUTAGENESIS; ROLES; OVEREXPRESSION; SUBSTITUTIONS; MECHANISM; RESIDUES AB Interaction between the alpha and beta subunits of tryptophan synthase leads to mutual stabilization of the active conformations and to coordinated control of the activities of the two subunits. To elucidate the roles of specific residues in the interaction site between the alpha and beta subunits, mutant alpha and beta subunits were constructed, and the effects of mutation on subunit interaction and intersubunit communication were determined. Mutation of either alpha subunit Asp56 (alpha D56A) or beta subunit Lys167 (beta K167T), residues that interact in some crystal structures of the tryptophan synthase alpha(2) beta(2) complex, decreases the ability of the alpha subunit to activate the beta subunit and alters the reaction and substrate specificity of the beta subunit. Partial conformational repair is provided by alpha-glycerol 3-phosphate, a ligand that binds to the alpha subunit, or by Cs+ or NH4+, ligands that bind to the beta subunit. Mutation of beta subunit Arg175 (beta R175A), a residue that interacts with alpha subunit Pro57 in some structures, has much smaller effects on activity but results in a 15-fold increase in the apparent K-d for dissociation of the alpha and beta subunits. Replacement of the single tryptophan in the beta subunit by phenylalanine (W177F) has only small effects on activity but increases the apparent subunit dissociation constant similar to 10-fold. The most important conclusions of this investigation are that interaction between alpha Asp56 and beta Lys167 is important for intersubunit communication and that mutual stabilization of the active conformations of the two subunits is impaired by mutation of either residue. C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Miles, EW (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bldg 8,Room 2A09, Bethesda, MD 20892 USA. NR 29 TC 32 Z9 32 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 MAR 3 PY 1998 VL 37 IS 9 BP 2961 EP 2968 DI 10.1021/bi972286z PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZB940 UT WOS:000072523600028 PM 9485448 ER PT J AU Wolf, DE McKinnon-Thompson, C Daou, MC Stephens, RM Kaplan, DR Ross, AH AF Wolf, DE McKinnon-Thompson, C Daou, MC Stephens, RM Kaplan, DR Ross, AH TI Mobility of TrkA is regulated by phosphorylation and interactions with the low-affinity NGF receptor SO BIOCHEMISTRY LA English DT Article ID NERVE GROWTH-FACTOR; NF-KAPPA-B; NEUROTROPHIN RECEPTOR; SIGNAL-TRANSDUCTION; LATERAL DIFFUSION; NEURONAL DIFFERENTIATION; TYROSINE KINASE; PC12 CELLS; AUTOPHOSPHORYLATION SITES; RETROGRADE TRANSPORT AB The nerve growth factor (NGF) receptor is a complex of two proteins, gp75 and the tyrosine kinase TrkA. Using fluorescence recovery after photobleaching, we have studied the diffusion properties of the TrkA receptor. For PC12 cells that express both gp75 and TrkA, TrkA was relatively immobile with only 28 +/- 1% of receptor molecules free to diffuse with D = (3.64 +/- 0.23) x 10(-9) cm(2)/s. Addition of NGF decreased the mobile fraction to 21 +/- 1% with D = (4.11 +/- 0.18) x 10(-9) cm(2)/s. Using the Sf9 baculovirus expression system, we were able to study TrkA in the absence and presence of gp75. On Sf9 cells, TrkA showed a mobile fraction of 46 +/- 2% with D = (2.64 +/- 0.21) x 10(-9) cm(2)/s in the absence of gp75 and 43 +/- 2% with D = (2.31 +/- 0.25) x 10(-9) cm(2)/s in its presence. Thus, gp75 did not alter TrkA mobility. Addition of NGF to the medium approximately halved the mobile fraction for TrkA in both the absence and presence of gp75. However, using a kinase-deficient mutant of TrkA, we found that ligand-induced immobilization requires an active kinase in the absence of gp75 but not in its presence. In addition, using point mutations at specific TrkA autophosphorylation sites, we determined that mobility is controlled by multiple phosphorylation sites, but the SHC binding site at Y490 may be particularly important for ligand-induced immobilization of TrkA. Therefore, two mechanisms lead to NGF-induced immobilization of TrkA-the first resulting from autophosphorylation of TrkA and the second occurring through TrkA's association with gp75. C1 Univ Massachusetts, Sch Med, Dept Physiol, Worcester, MA 01655 USA. Univ Massachusetts, Sch Med, Dept Pharmacol, Worcester, MA 01655 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21701 USA. Montreal Neurol Inst, Quebec City, PQ H3A 2B4, Canada. RP Wolf, DE (reprint author), Univ Massachusetts, Sch Med, Dept Physiol, 55 Lake Ave N, Worcester, MA 01655 USA. FU NINDS NIH HHS [NS21716, NS28760] NR 69 TC 13 Z9 14 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 3 PY 1998 VL 37 IS 9 BP 3178 EP 3186 DI 10.1021/bi9719253 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZB940 UT WOS:000072523600052 PM 9485472 ER PT J AU Jones, TLZ Gutkind, JS AF Jones, TLZ Gutkind, JS TI G alpha(12) requires acylation for its transforming activity SO BIOCHEMISTRY LA English DT Article ID PROTEIN-ALPHA-SUBUNIT; GTP-BINDING PROTEINS; MEMBRANE ATTACHMENT; AMINO-TERMINUS; KINASE-C; LIPID MODIFICATIONS; PLASMA-MEMBRANE; BETA-GAMMA; PALMITOYLATION; G(12) AB The alpha subunit of the heterotrimeric G protein G(12), harboring a mutation in the GTP binding domain (Q229L), behaves as a potent oncogene in NIH 3T3 cells. This alpha subunit, like most other G protein alpha subunits, undergoes palmitoylation, the reversible posttranslational addition of palmitate to cysteine residues. We investigated the role of palmitoylation of alpha(12) in membrane localization and transformation efficiency and whether another lipid modification, myristoylation, could substitute for palmitoylation. NIH 3T3 cells were stably transfected with plasmids that expressed the wild-type alpha(12), the constitutively active Q229L (QL) mutant, and mutants in which C11 was changed to S (C11S) and S2 and R6 were changed to G and S, respectively (S2G). Incorporation of [H-3]palmitate was found in the endogenous and expressed alpha(12) but not in the C11S mutants. Incorporation of [H-3]myristate was found only in the S2G mutants. The wild type, QL mutant, and all the acylation mutants were found in the particulate fraction. Cells expressing the nonpalmitoylated C11S,QL mutant did not undergo transformation. The S2G mutation in the nonpalmitoylated C11S,QL mutant restored the transformation efficiency to a greater level than that of the palmitoylated QL mutant as measured by foci formation, growth in soft agar, and growth rate. Palmitoylation was critical for the transformation efficiency of alpha(12) but not specifically required because myristoylation could substitute for these functions. C1 NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NIDR, Cellular Dev & Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Jones, TLZ (reprint author), NIDDK, Metab Dis Branch, NIH, Bldg 10,Room 8C101, Bethesda, MD 20892 USA. EM tlzj@helix.nih.gov RI Gutkind, J. Silvio/A-1053-2009 NR 61 TC 27 Z9 28 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 3 PY 1998 VL 37 IS 9 BP 3196 EP 3202 DI 10.1021/bi972253j PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZB940 UT WOS:000072523600054 PM 9485474 ER PT J AU Husain, S Andrews, NP Mulcahy, D Panza, JA Quyyumi, AA AF Husain, S Andrews, NP Mulcahy, D Panza, JA Quyyumi, AA TI Aspirin improves endothelial dysfunction in atherosclerosis SO CIRCULATION LA English DT Article DE endothelium-derived factors; aspirin; atherosclerosis ID CONGESTIVE-HEART-FAILURE; NORMAL CORONARY-ARTERIES; CANINE FEMORAL-ARTERY; NITRIC-OXIDE; DEPENDENT CONTRACTIONS; VASOMOTOR RESPONSE; RELAXING FACTOR; SMOOTH-MUSCLE; ARACHIDONIC-ACID; ELEVATED GLUCOSE AB Background-The beneficial effects of aspirin in atherosclerosis are generally attributed to its antiplatelet activities, but its influence on endothelial function remains uncertain. Wie hypothesized that a cyclooxygenase-dependent constricting factor contributes to the endothelial dysfunction in atherosclerosis and that its action call be reversed by aspirin. Methods and Results-In 14 patients with coronary atherosclerosis and 5 with risk factors, we tested femoral vascular endothelial function with acetylcholine and substance P and endothelium-independent function with sodium nitroprusside before and after intravenous aspirin. Drug were infused into the femoral artery, and Doppler flow velocity was measured. Acetylcholine-induced but trot substance P-or sodium nitroprusside-induced vasodilation was lower-in patients with atherosclerosis than in those with only risk factors, Aspirin had no baseline effect but improved acetylcholine-mediated vasodilation only ill patients with atherosclerosis; at the peak dose, acetylcholine-mediated femoral vascular resistance index was 19+/-5%, P=.002 lower, There was a correlation between the baseline response to acetylcholine and the magnitude of improvement with aspirin (r=.5, P=.05). Thus, patients with a depressed response to acetylcholine had greater improvement with aspirin, and vice vena. The presence of atherosclerosis was as an independent determinant of improvement with aspirin. Aspirin had Ilo effect art the responses to either substance P or sodium nitroprusside. Conclusions-Cyclooxygenase-dependent, endothelium-derived vasoconstrictor release modulates acetylcholine-induced peripheral vasodilation in patients with atherosclerosis. Improvement of endothelial dysfunction with aspirin may improve vasodilation, reduce thrombosis, and inhibit progression of atherosclerosis and provides a pathophysiological basis for the beneficial effects of aspirin in atherosclerosis. C1 NHLBI, Cardiol Branch, Bethesda, MD 20892 USA. RP Quyyumi, AA (reprint author), NHLBI, Cardiol Branch, Bldg 10,10 Ctr Dr,MSC 1650,Room 7B15, Bethesda, MD 20892 USA. EM quyyumia@gwgate.nhlbi.nih.gov NR 52 TC 177 Z9 190 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 3 PY 1998 VL 97 IS 8 BP 716 EP 720 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YY916 UT WOS:000072200800003 PM 9498533 ER PT J AU Pankow, JS Beck, JD Offenbacher, S Tyroler, HA Nieto, J Sharrett, R Heiss, G AF Pankow, JS Beck, JD Offenbacher, S Tyroler, HA Nieto, J Sharrett, R Heiss, G TI Association of periodontal disease and cardiovascular disease risk factors SO CIRCULATION LA English DT Meeting Abstract C1 Univ N Carolina, Chapel Hill, NC 27515 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 3 PY 1998 VL 97 IS 8 MA 3 BP 814 EP 814 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YY916 UT WOS:000072200800022 ER PT J AU Meigs, JB Mittleman, MA Ordovas, JM Cupples, LA D'Agostino, RB Singer, DE Nathan, DM Schaefer, EJ Tofler, GH Wilson, PWF AF Meigs, JB Mittleman, MA Ordovas, JM Cupples, LA D'Agostino, RB Singer, DE Nathan, DM Schaefer, EJ Tofler, GH Wilson, PWF TI Plasminogen activator inhibitor-1 and small dense low density lipoprotein levels in the insulin resistance syndrome: The Framingham Offspring Study SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Med Ctr, IPCD, Boston, MA USA. Tufts Univ, JM, USDA, HNRCA, Medford, MA 02155 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. NHLBI, Framingham Heart Study, NIH, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 3 PY 1998 VL 97 IS 8 MA 9 BP 815 EP 815 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YY916 UT WOS:000072200800028 ER PT J AU Schreiner, PJ Chambless, LE Folsom, AR Rosamond, WD Cooper, LS Morrisett, JD AF Schreiner, PJ Chambless, LE Folsom, AR Rosamond, WD Cooper, LS Morrisett, JD TI Lipoprotein[a] and incident ischemic stroke: The ARIC study SO CIRCULATION LA English DT Meeting Abstract C1 Univ Minnesota, Minneapolis, MN 55455 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Univ Minnesota, Minneapolis, MN 55455 USA. NHLBI, Bethesda, MD 20892 USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 3 PY 1998 VL 97 IS 8 MA 28 BP 818 EP 818 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YY916 UT WOS:000072200800047 ER PT J AU Burchfiel, CM Rodriguez, BL Abbott, RD Sharp, DS Curb, JD AF Burchfiel, CM Rodriguez, BL Abbott, RD Sharp, DS Curb, JD TI Insulin levels and risk of stroke: The Honolulu Heart Program. SO CIRCULATION LA English DT Meeting Abstract C1 Univ Virginia, Charlottesville, VA USA. Univ Hawaii, Honolulu, HI 96822 USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 3 PY 1998 VL 97 IS 8 MA P34 BP 824 EP 824 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YY916 UT WOS:000072200800085 ER PT J AU Rosamond, WD Folson, AR Chambless, LE McGovern, P Howard, G Cooper, L Shahar, E AF Rosamond, WD Folson, AR Chambless, LE McGovern, P Howard, G Cooper, L Shahar, E TI Stroke incidence rates: Seven year follow-up of the atherosclerosis risk in communities (ARIC) cohort SO CIRCULATION LA English DT Meeting Abstract C1 Univ Minnesota, Minneapolis, MN USA. NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 3 PY 1998 VL 97 IS 8 MA P31 BP 824 EP 824 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YY916 UT WOS:000072200800082 ER PT J AU Cushman, WC Crespo, CJ Roccella, EJ AF Cushman, WC Crespo, CJ Roccella, EJ TI The prevalence of Stage 1 and Stage 2+ isolated systolic hypertension in the United States (1988-94). SO CIRCULATION LA English DT Meeting Abstract C1 Vet Affairs Med Ctr, Memphis, TN USA. American Univ, Washington, DC 20016 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 3 PY 1998 VL 97 IS 8 MA P39 BP 825 EP 825 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YY916 UT WOS:000072200800090 ER EF