FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Gladyshev, VN Hatfield, DL AF Gladyshev, VN Hatfield, DL TI Selenocysteine-containing proteins in mammals SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Review DE selenocysteine; selenoproteins; selenoenzymes; glutathione peroxidase; iodothyronine deiodinase; thioredoxin reductase; selenoprotein P; codon UGA ID HUMAN THIOREDOXIN REDUCTASE; NICOTINIC-ACID HYDROXYLASE; HYDROPEROXIDE GLUTATHIONE-PEROXIDASE; LUNG ADENOCARCINOMA CELLS; CONTAINING TRANSFER-RNAS; 3' UNTRANSLATED REGION; OPEN READING FRAME; SELENOPROTEIN-P; CLOSTRIDIUM-BARKERI; CANCER-CELLS AB Since the recent discovery of selenocysteine as the 21st amino acid in protein, the field of selenium biology has rapidly expanded. Twelve mammalian selenoproteins have been characterized to date and each contains selenocysteine that is incorporated in response to specific UGA code words. These selenoproteins have different cellular functions, but in those selenoproteins for which the function is known, selenocysteine is located at the active center. The presence of selenocysteine at critical sites in naturally occurring selenoproteins provides an explanation for the important role of selenium in human health and development. This review describes known mammalian selenoproteins and discusses recent developments and future directions in the selenium field. C1 Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. NCI, Sect Mol Biol Selenium, Basic Res Lab,Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Gladyshev, VN (reprint author), Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. RI Gladyshev, Vadim/A-9894-2013 NR 103 TC 108 Z9 113 U1 1 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD MAY-JUN PY 1999 VL 6 IS 3 BP 151 EP 160 DI 10.1007/BF02255899 PG 10 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 195YE UT WOS:000080279200002 PM 10343164 ER PT J AU Nieland, JD Da Silva, DM Velders, MP de Visser, KE Schiller, JT Muller, M Kast, WM AF Nieland, JD Da Silva, DM Velders, MP de Visser, KE Schiller, JT Muller, M Kast, WM TI Chimeric papillomavirus virus-like particles induce a murine self-antigen-specific protective and therapeutic antitumor immune response SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE chimeric virus-like particles; peptide-induced tolerance; immunotherapy; P815; P1A ID CYTOTOXIC T-LYMPHOCYTES; DENDRITIC CELLS; PEPTIDE VACCINATION; TUMOR OUTGROWTH; CANCER; L1; IMMUNOTHERAPY; VACCINES; EPITOPES; ELICIT AB The use of chimeric virus-like particles represents a new strategy for delivering tumor antigens to the immune system for the initiation of antitumor immune responses. Immunization of DBA/2 mice with the P1A peptide derived from the P815 tumor-associated antigen P1A induced specific T-cell tolerance, resulting in progression of a regressor P815 cell line in all animals. However, immunization with a human papillomavirus type 16 L1 virus-like particle containing the P1A peptide in the absence of adjuvant induced a protective immune response in mice against a lethal tumor challenge with a progressor P815 tumor cell line. Additionally, we demonstrated that these chimeric virus-like particles could be used therapeutically to suppress the growth of established tumors, resulting in a significant survival advantage for chimeric virus-like particle-treated mice compared with untreated control mice. Chimeric virus-like particles can thus be used as a universal delivery vehicle for both tolerizing and antigenic peptides to induce a strong protective and therapeutic antigen-specific antitumor immune response. (C) 1999 Wiley-Liss, Inc. C1 Loyola Univ, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. Loyola Univ, Dept Microbiol & Immunol, Maywood, IL 60153 USA. NIH, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Kast, WM (reprint author), Loyola Univ, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. FU NCI NIH HHS [P01-CA74182, R01-CA/AI78399]; NIAID NIH HHS [T32 AI07508] NR 26 TC 44 Z9 46 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAY 1 PY 1999 VL 73 IS 2 BP 145 EP 152 DI 10.1002/(SICI)1097-4644(19990501)73:2<145::AID-JCB1>3.0.CO;2-5 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 183JV UT WOS:000079551200001 PM 10227378 ER PT J AU Shelly, LL Fuchs, C Miele, L AF Shelly, LL Fuchs, C Miele, L TI Notch-1 inhibits apoptosis in murine erythroleukemia cells and is necessary for differentiation induced by hybrid polar compounds SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE differentiation-inducing drugs; apoptosis; cancer; notch-1 ID HEXAMETHYLENE BISACETAMIDE; INTRACELLULAR DOMAIN; NEOPLASTIC LESIONS; TRANSFORMED-CELLS; DROSOPHILA NOTCH; HUMAN HOMOLOG; GENE; EXPRESSION; LEUKEMIA; PROTEINS AB Strikingly increased expression of notch-1 has been demonstrated in several human malignancies and pre-neoplastic lesions. However, the functional consequences of notch-1 overexpression in transformed cells remain unclear. We investigated whether endogenously expressed notch-1 controls cell Fate determination in mouse erythroleukemia (MEL) cells during pharmacologically induced differentiation. We found that notch-1 expression is modulated during MEL cell differentiation. Premature downregulatian of notch-1 during differentiation, by antisense S-oligonucleotides or by enforced expression of antisense notch-1 mRNA, causes MEL cells to abort the differentiation program and undergo apoptosis. Downregulation of notch-1 expression in the absence of differentiation inducer increases the likelihood of spontaneous apoptosis. We conclude that in MEL cells, endogenous notch-1 expression controls the apoptotic threshold during differentiation and growth. In these cells, notch-1 allows differentiation by preventing apoptosis of pre-committed cells. This novel function of notch-1 may play a role in regulating apoptosis susceptibility in notch-1 expressing tumor cells. (C) 1999 Wiley-Liss, Inc. C1 Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. NIH, Cell Biol Lab, Ctr Biol Evaluat & Res, Food & Drug Adm, Bethesda, MD 20892 USA. RP Miele, L (reprint author), Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, Room 204,2160 S 1st Ave, Maywood, IL 60153 USA. EM lmiele@luc.edu NR 40 TC 92 Z9 95 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAY 1 PY 1999 VL 73 IS 2 BP 164 EP 175 DI 10.1002/(SICI)1097-4644(19990501)73:2<164::AID-JCB3>3.0.CO;2-0 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 183JV UT WOS:000079551200003 PM 10227380 ER PT J AU Romanova, LY Alexandrov, IA Blagosklonny, MV Nordan, RP Garfield, S Acs, P Nguyen, P Trepel, J Blumberg, PM Mushinski, JF AF Romanova, LY Alexandrov, IA Blagosklonny, MV Nordan, RP Garfield, S Acs, P Nguyen, P Trepel, J Blumberg, PM Mushinski, JF TI Regulation of actin cytoskeleton in lymphocytes: PKC-delta disrupts IL-3-induced membrane ruffles downstream of Rac1 SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID PROTEIN-KINASE-C; FOCAL ADHESION KINASE; CELL-CYCLE PROGRESSION; TYROSINE PHOSPHORYLATION; PHORBOL ESTER; GROWTH-FACTOR; LEUKEMIA-CELLS; CDC42 GTPASES; MAP KINASE; CROSS-TALK AB In the murine pre-B lymphoid cell line Baf3, the presence of IL-3 is required for the formation of membrane ruffles that intensely stain for actin and are responsible for the elongated cell phenotype. Withdrawal of IL-3 dissolves ruffled protrusions and converts the cell phenotype to round. Flow cytometric analysis of the cell shape showed that an inactive analog of Rad but not inactive RhoA or inactive cdc42 rounds the cells in the presence of IL-3. Constitutively activated Rad restores the elongated cell phenotype to IL-3-starved cells. We conclude that the activity of Rad is necessary and sufficient for the IL-3-induced assembly of membrane ruffles. Similar to the IL-3 withdrawal, phorbol 12-myristate 13-acetate (PMA) dissolves actin-formed membrane ruffles and rounds the cells in the presence of IL-3. Flow cytometric analysis of the cell shape demonstrated that in the presence of IL-3 the PMA-induced cell rounding cannot be abolished by constitutively active Rad but can be imitated by inactive Rad. These data indicate that PMA disrupts the IL-3 pathway downstream of Rad. Cells rounded by PMA return to the elongated phenotype concomitantly with PKC depletion. PMA-induced cell rounding can be reversed by the PKC-specific inhibitor GF109203X. Experiments with overexpression in Baf3 of individual PKC isoforms and a dominant negative PKC-delta indicate that activation of PKC-delta but not other PKC isoforms is responsible for disruption of membrane ruffles. Published 1999 Wiley-Liss, Inc.(dagger) C1 NIH, NCI, Genet Lab, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. RP Romanova, LY (reprint author), NIH, NCI, Genet Lab, Bldg 37,Rm 2B23,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM romanovl@dc37a.nci.nih.gov NR 45 TC 16 Z9 20 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAY PY 1999 VL 179 IS 2 BP 157 EP 169 DI 10.1002/(SICI)1097-4652(199905)179:2<157::AID-JCP6>3.0.CO;2-4 PG 13 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 183KU UT WOS:000079553400006 PM 10199555 ER PT J AU Schmidt, K AF Schmidt, K TI Which linear compartmental systems can be analyzed by spectral analysis of PET output data summed over all compartments? SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE kinetic modeling; tracer kinetics ID CEREBRAL GLUCOSE-UTILIZATION; POSITRON EMISSION TOMOGRAPHY; BRAIN TRANSFER CONSTANTS; TIME UPTAKE DATA; F-18 FLUORODEOXYGLUCOSE; GRAPHICAL EVALUATION; MODELS; KINETICS; DOPA AB General linear rime-invariant compartmental systems were examined to determine which systems meet the conditions necessary for application of the spectral analysis technique to the sum of the concentrations in all compartments. Spectral analysis can be used to characterize the reversible and irreversible components of the system and to estimate the minimum number of compartments, but it applies only to systems in which the measured data can be expressed as a positively weighted sum of convolution integrals of the input function with an exponential function that has real-valued nonpositive decay constants. The conditions are met by compartmental systems that are strongly connected, have exchange of material with the environment confined to a single compartment, and do not contain cycles, i.e., there is no possibility for material to pass from one compartment through two or more compartments back ro the initial compartment. Certain noncyclic systems with traps, systems with cycles that obey a specified loop condition, and noninterconnected collections of such systems also meet the conditions. Dynamic positron emission tomographic data obtained after injection of a radiotracer, the kinetics of which can be described by any model in the class of models identified here, can be appropriately analyzed with the spectral analysis technique. C1 NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. RP Schmidt, K (reprint author), NIMH, Cerebral Metab Lab, Bldg 36,Room 1A-07,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 25 TC 18 Z9 18 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAY PY 1999 VL 19 IS 5 BP 560 EP 569 PG 10 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 277TA UT WOS:000084948600010 PM 10326723 ER PT J AU Chmielowska, J Coghill, RC Carson, RE Ishii, K Chen, R Hallett, M Herscovitch, P AF Chmielowska, J Coghill, RC Carson, RE Ishii, K Chen, R Hallett, M Herscovitch, P TI Comparison of PET [O-15]water studies with 6-minute and 10-minute interscan intervals: Single-subject and group analyses SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE positron-emission tomography; [O-15]water; activation studies; interscan interval ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL BLOOD-FLOW; AUTOMATED ALGORITHM; SAMPLE SIZES; ACTIVATION AB The authors recently showed that [O-15]water PET data obtained with a short interscan interval (6 minutes) produced similar results whether or not the residual background from the previous scan is subtracted. The purpose of the present study was to compare scans obtained during motor activation using a short (6-minute) interscan interval protocol with those obtained with a standard (10-minute) protocol in the same scanning session. Single-subject and group analyses were performed using Worsley's method, which uses a pooled variance estimate and statistical parametric mapping with a local variance estimate. High consistency in both the activation maps, i.e., the number of activated motor brain structures and the Talairach coordinates of peak intensities of the activated regions, was obtained in the 6- and 10-minute studies in both single-subject and group analyses. However, in comparison to the 6-minute studies, a larger cluster size of activated brain regions and an approximately 20% higher peak activation in these regions were observed in the 10-minute studies with the same number of replicates. Analysis of these results suggests that using a 6-minute interval with an increased number of replications, i.e., without changing the subject's total study duration, should produce comparable statistical power to that of the 10-minute interval for group analysis and increased statistical power for single-subject analyses that use a local variance estimate because of increased degrees of freedom. Alternatively, with a small increase in the number of scans and the use of a 6-minute interscan interval, a comparable level of statistical significance may be achieved for single-subject experiments that use a local variance estimate, with an overall shortening of the study duration. C1 NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. NIDR, Pain & Neurosensory Mechanisms Branch, NIH, Bethesda, MD 20892 USA. RP Herscovitch, P (reprint author), NIH, PET Dept, Ctr Clin, Bldg 10,Room 1C401,10 Ctr Dr MSC 1180, Bethesda, MD 20892 USA. RI Chen, Robert/B-3899-2009; Carson, Richard/H-3250-2011 OI Chen, Robert/0000-0002-8371-8629; Carson, Richard/0000-0002-9338-7966 NR 23 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAY PY 1999 VL 19 IS 5 BP 570 EP 582 PG 13 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 277TA UT WOS:000084948600011 PM 10326724 ER PT J AU Jones, TH Gorman, JST Snelling, RR Delabie, JHC Blum, MS Garraffo, HM Jain, P Daly, JW Spande, TF AF Jones, TH Gorman, JST Snelling, RR Delabie, JHC Blum, MS Garraffo, HM Jain, P Daly, JW Spande, TF TI Further alkaloids common to ants and frogs: Decahydroquinolines and a quinolizidine SO JOURNAL OF CHEMICAL ECOLOGY LA English DT Article DE alkaloids; mass spectrometry; infrared spectroscopy; amphibians; ants; decahydroquinolines; quinolizidines ID POISON FROGS; SKIN ALKALOIDS; DENDROBATIDAE; CHEMISTRY; VENOM; PYRROLIZIDINES; PUMILIOTOXINS; INDOLIZIDINES; MANTELLA AB Three alkaloids-two minor decahydroquinolines (DHQs) and a major quinolizidine-were detected in an extract of a Brazilian myrmicine ant (Solenopsis (Diplorhoptrum) sp. picea group). One DHQ (3) was identical to a known frog-skin alkaloid, cis-195A (cis-5-methyl-2-propyldecahydroquinoline), while the second DHQ, an isomer of 3, designated 195J, was assigned a tentative cis-2-methyl-5-propyldecahydroquinoline structure (2) based on mass and infrared spectra. The third alkaloid proved identical to the frog-skin alkaloid 195C, for which a structure had not been previously proposed. Mass and infrared spectral analysis, including chemical ionization tandem mass spectrometry, indicated a 4-methyl-6-propylquinolizidine structure (1) for 195C. The four possible diastereomers were synthesized and the (6Z,10E)-4-methyl-6-propylquinolizidine diastereomer (1b) was identical to the natural alkaloid. Skin extracts of a population of a Madagascan mantelline frog contained, among other alkaloids, minor amounts of the same alkaloid triad 1-3 with 1 again predominating. The common occurrence of alkaloids 1-3 in both ant and frog supports the hypothesis that ants are a likely dietary source for sequestered frog-skin alkaloids and brings to six, the alkaloid classes common to ant and frog. C1 Virginia Mil Inst, Dept Chem, Lexington, VA 24450 USA. Los Angeles Cty Museum Nat Hist, Los Angeles, CA 90007 USA. CEPLAC, Ctr Pesquesa Cacau, Div Zool, BR-15600 Itabuna, BA, Brazil. Univ Georgia, Dept Entomol, Athens, GA 30602 USA. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Jones, TH (reprint author), Virginia Mil Inst, Dept Chem, Lexington, VA 24450 USA. RI Delabie, Jacques/F-3405-2010 OI Delabie, Jacques/0000-0002-2695-1061 NR 31 TC 90 Z9 94 U1 0 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0098-0331 EI 1573-1561 J9 J CHEM ECOL JI J. Chem. Ecol. PD MAY PY 1999 VL 25 IS 5 BP 1179 EP 1193 DI 10.1023/A:1020898229304 PG 15 WC Biochemistry & Molecular Biology; Ecology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology GA 195TG UT WOS:000080267800015 ER PT J AU Sarlis, NJ Weil, SJ Nelson, LM AF Sarlis, NJ Weil, SJ Nelson, LM TI Administration of metformin to a diabetic woman with extreme hyperandrogenemia of nontumoral origin: Management of infertility and prevention of inadvertent masculinization of a female fetus SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID POLYCYSTIC-OVARY-SYNDROME; INSULIN-RESISTANCE; FREE TESTOSTERONE; PREGNANCY; DISEASE; VIRILIZATION; THERAPY; PSEUDOHERMAPHRODITISM; HYPERINSULINEMIA; REDUCTION C1 NIDDKD, Mol & Cellular Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Sarlis, NJ (reprint author), NIDDKD, Mol & Cellular Endocrinol Branch, NIH, Bldg 10,Room 8D12C,10 Ctr Dr,MSC 1758, Bethesda, MD 20892 USA. EM njsarlis@box-n.nih.gov NR 28 TC 23 Z9 23 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1999 VL 84 IS 5 BP 1510 EP 1512 DI 10.1210/jc.84.5.1510 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 193MZ UT WOS:000080141600004 PM 10323370 ER PT J AU Bornstein, SR Chrousos, GP AF Bornstein, SR Chrousos, GP TI Adrenocorticotropin (ACTH)- and non-ACTH-mediated regulation of the adrenal cortex: Neural and immune inputs SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID CORTICOTROPIN-RELEASING HORMONE; TUMOR-NECROSIS-FACTOR; GASTRIC-INHIBITORY POLYPEPTIDE; GLAND IN-VIVO; CUSHINGS-SYNDROME; CHROMAFFIN CELLS; CORTICAL-CELLS; SYMPATHOADRENAL REGULATION; NEUROENDOCRINE REGULATION; INTRAADRENAL INTERACTIONS C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Bornstein, SR (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N242,10 Ctr Dr, Bethesda, MD 20892 USA. NR 100 TC 218 Z9 222 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1999 VL 84 IS 5 BP 1729 EP 1736 DI 10.1210/jc.84.5.1729 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 193MZ UT WOS:000080141600044 PM 10323408 ER PT J AU Stetler-Stevenson, WG AF Stetler-Stevenson, WG TI Matrix metalloproteinases in angiogenesis: a moving target for therapeutic intervention SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID FIBROBLAST GROWTH-FACTOR; TISSUE INHIBITOR; ANGIOSTATIN; EXPRESSION; TIMP-2; CELLS; NEOVASCULARIZATION; ALPHA-V-BETA-3; COLLAGENASE; PROPEPTIDE C1 NCI, Div Clin Sci, Pathol Lab, Extracellular Matrix Pathol Sect, Bethesda, MD 20892 USA. RP Stetler-Stevenson, WG (reprint author), NCI, Div Clin Sci, Pathol Lab, Extracellular Matrix Pathol Sect, Bldg 10,Room 2A33,MSC 1500,10 Ctr Dr, Bethesda, MD 20892 USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 24 TC 544 Z9 564 U1 3 U2 9 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 1999 VL 103 IS 9 BP 1237 EP 1241 DI 10.1172/JCI6870 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 194PT UT WOS:000080203300004 PM 10225966 ER PT J AU Darling, TN Yee, C Bauer, JW Hintner, H Yancey, KB AF Darling, TN Yee, C Bauer, JW Hintner, H Yancey, KB TI Revertant mosaicism: partial correction of a germ-line mutation in COL17A1 by a frame-restoring mutation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BENIGN EPIDERMOLYSIS-BULLOSA; LASER CAPTURE MICRODISSECTION; DYSTROPHIN-POSITIVE FIBERS; PEMPHIGOID ANTIGEN BPAG2; 5 AUSTRIAN FAMILIES; XVII COLLAGEN GENE; DELETION MUTATION; SOMATIC MOSAICISM; BASEMENT-MEMBRANE; CELLS AB Generalized atrophic benign epidermolysis bullosa is an autosomal recessive subepidermal blistering disease typified by null mutations in COL17A1. In 1 large kindred, affected individuals were homozygous for a 2-bp deletion in COL17A1, 4003delTC, which resulted in a downstream premature termination codon, nonsense-mediated mRNA decay, and abrogation of type XVII collagen synthesis. Interestingly, 1 of these patients, although phenotypically identical to her affected siblings, showed focal expression of type XVII collagen in epidermal basement membrane in a pattern suggestive of revertant mosaicism. When studies of randomly obtained epidermal, oromucosal, and peripheral blood cells failed to identify the genetic basis of this apparent mosaicism, microscopic subpopulations of potentially revertant epidermal cells (i.e., those overlying basement membrane containing type XVII collagen) were selectively isolated using laser capture microdissection. Analysis of DNA and RNA from these cells revealed a second mutation, 4080insGG, on 1 allele of COL17A1. This 2-bp insertion corrected the reading frame just proximal to the premature termination codon, countered nonsense-mediated mRNA decay, and allowed protein production by patient keratinocytes in vivo and in vitro. These studies elucidate the molecular basis of a novel form of revertant mosaicism in humans. C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. Gen Hosp, Dept Dermatol, A-5020 Salzburg, Austria. RP Darling, TN (reprint author), NCI, Dermatol Branch, NIH, Bldg 10,Room 12N238,10 Ctr Dr MSC 1908, Bethesda, MD 20892 USA. OI Darling, Thomas/0000-0002-5161-1974 NR 28 TC 46 Z9 47 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 1999 VL 103 IS 10 BP 1371 EP 1377 DI 10.1172/JCI4338 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251VN UT WOS:000083467200003 PM 10330419 ER PT J AU Rocca, B Spain, LM Pure, E Langenbach, R Patrono, C FitzGerald, GA AF Rocca, B Spain, LM Pure, E Langenbach, R Patrono, C FitzGerald, GA TI Distinct roles of prostaglandin H synthases 1 and 2 in T-cell development SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID THYMIC EPITHELIAL-CELLS; CYCLOOXYGENASE ACTIVITY; ENDOPEROXIDE SYNTHASES; PROSTANOID RECEPTORS; MONOCLONAL-ANTIBODY; ARACHIDONIC-ACID; GENE DISRUPTION; B-LYMPHOCYTES; HUMAN TISSUES; THYMOCYTES AB Prostaglandin G and H synthases, or cyclooxygenases (COXs), catalyze the formation of prostaglandins (PGs). Whereas COX-1 is diffusely expressed in lymphoid cells in embryonic day 15.5 thymus, COX-2 expression is sparse, apparently limited to stromal cells. By contrast, COX-2 is predominant in a subset of medullary stromal cells in three- to five-week-old mice. The isozymes also differ in their contributions to lymphocyte development. Thus, experiments with selective COX-1 inhibitors in thymic lobes from normal and recombinase-activating gene-1 knockout mice support a role for this isoform in the transition from CD4(-)CD8(-) double-negative (DN) to CD4(+)CD8(+) double-positive (DP). Concordant data were obtained in COX-I knockouts. Pharmacological inhibition and genetic deletion of COX-2, by contrast, support its role during early thymocyte proliferation and differentiation and, later, during maturation of the CD4 helper T-cell Lineage. PGE(2), but not other PGs, can rescue the effects of inhibition of either isoform, although it acts through distinct EP receptor subtypes. COX-dependent PG generation may represent a mechanism of thymic stromal support for T-cell development. C1 Univ Penn, Ctr Expt Therapeut, Philadelphia, PA 19104 USA. Wistar Inst, Philadelphia, PA 19104 USA. NIEHS, Lab Expt Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. Univ Chieti, Sch Med, Dept Med & Aging, Chieti, Italy. RP FitzGerald, GA (reprint author), Univ Penn, Ctr Expt Therapeut, 153 Johnston Pavill, Philadelphia, PA 19104 USA. RI FitzGerald, Garret/A-4222-2010 FU NHLBI NIH HHS [HL-54500, HL-57847, P50 HL054500] NR 51 TC 105 Z9 106 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 1999 VL 103 IS 10 BP 1469 EP 1477 DI 10.1172/JCI6400 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251VN UT WOS:000083467200013 PM 10330429 ER PT J AU Girdner, JL Cullen, AP Salama, TG He, L Lorincz, A Quinn, TC AF Girdner, JL Cullen, AP Salama, TG He, L Lorincz, A Quinn, TC TI Evaluation of the digene hybrid capture II CT-ID test for detection of Chlamydia trachomatis in endocervical specimens SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; REACTION ASSAY; GENITAL SPECIMENS; URINE SPECIMENS; CELL-CULTURE; INFECTIONS; DIAGNOSIS; WOMEN; TEMPERATURE; STORAGE AB The performance characteristics of the new signal amplification-based Hybrid Capture (HC) II CT-ID test system (Digene, Silver Spring, Md.) with endocervical specimens were compared to those of tissue culture and PCR (AMPLICOR CT PCR; Roche Molecular Systems, Branchburg, N.J.) for detection of Chlamydia trachomatis in 587 women. HC II CT-ID identified 62 of 65 confirmed C. trachomatis-positive patients (sensitivity of 95.4%) and was negative for 517 of 522 patients who were negative by culture and PCR (specificity of 99.0%). Twelve of the 65 confirmed positive patients were negative by culture but sere identified by both HC II CT-ID and PCR (sensitivity of culture was 81.5% [P < 0.01]). In comparison, PCR detected 59 of 65 positive specimens (sensitivity of 90.8%) and had a specificity of 99.6% (520 of 522). These results demonstrate that the Digene HC II CT-ID test is a highly sensitive and specific assay for the detection of C. trachomatis infection in endocervical specimens. C1 Johns Hopkins Univ, Div Infect Dis, Baltimore, MD 21205 USA. Baltimore City Hlth Dept, Baltimore, MD USA. Digene Corp, Silver Spring, MD USA. NIAID, Bethesda, MD 20892 USA. RP Quinn, TC (reprint author), Johns Hopkins Univ, Div Infect Dis, 720 Rutland Ave,Ross Research Bldg 1159, Baltimore, MD 21205 USA. NR 19 TC 23 Z9 23 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 1999 VL 37 IS 5 BP 1579 EP 1581 PG 3 WC Microbiology SC Microbiology GA 187NG UT WOS:000079792400065 PM 10203527 ER PT J AU Mamounas, E Wieand, S Wolmark, N Bear, HD Atkins, JN Song, K Jones, J Rockette, H AF Mamounas, E Wieand, S Wolmark, N Bear, HD Atkins, JN Song, K Jones, J Rockette, H TI Comparative efficacy of adjuvant chemotherapy in patients with Dukes' B versus Dukes' c colon cancer: Results from four national surgical adjuvant breast and bowel project adjuvant studies (C-01, C-02, C-03, and C-04) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FLUOROURACIL PLUS LEVAMISOLE; COLORECTAL-CANCER; THERAPY; PROGNOSIS; CARCINOMA AB Purpose: Although the benefit from adjuvant chemotherapy has been clearly established in patients with Dukes' C colon cancer, such benefit has been questioned in patients with Dykes' B disease. To determine whether patients with Dukes' B disease benefit from adjuvant chemotherapy and to evaluate the magnitude of the benefit, compared with that observed in Dukes' C patients, we examined the relative efficacy of adjuvant chemotherapy according to Dukes' stage in four sequential National Surgical Adjuvant Breast and Dowel Project trials (C-01,C-02, C-03, and C-04) that compared different adjuvant chemotherapy regimens with each other or with no adjuvant treatment. Patients and Methods: The four trials included Dukes' B and C patients and were conducted between 1977 and 1990. The eligibility criteria and follow-up requirements were similar for all four trials. Protocol C-01 compared adjuvant semustine, vincristine, and fluorouracil(5-FU) (MOF regimen) with operation alone. Protocol C-02 compared the perioperative administration of a portal venous infusion of 5-FU with operation alone. Protocol C-03 compared adjuvant 5-FU and leucovorin (LV) with adjuvant MOF. Protocol C-04 compared adjuvant 5-FU and LV with 5-FU and levamisole (LEV) and with the combination of 5-FU, LV,and LEV. Results: Forty-one percent of the patients included in these four trials had resected Dykes' B tumors. In all four studies, the overall, disease-free, and recurrence-free survival improvement noted for all patients was evident in both Dukes' B and Dykes' C patients. When the relative efficacy of chemotherapy was examined, there was always an observed reduction in mortality, recurrence, or disease-free survival event, irrespective of Dukes' stage, and in most instances, the reduction was as great or greater for Dykes' B patients as for Dykes' C patients. When data from all four trials were examined in a combined analysis, the mortality reduction was 30% for Dukes' B patients versus 18% for Dykes' C patients. The mortality reduction in Dukes' B patients occurred irrespective of the presence or absence of adverse prognostic factors. Conclusion: Patients with Dukes' B colon cancer benefit from adjuvant chemotherapy and should be presented with this treatment option. Regardless of the presence or absence of other clinical prognostic factors, Dukes' B patients seem to benefit from chemotherapy administration. J Clin Oncol 17:1349-1355. (C) 1999 by American Society of Clinical Oncology. C1 Natl Surg Adjuvant Breast & Bowel Project, Allegheny Ctr 4, Operat Ctr, Pittsburgh, PA 15212 USA. Natl Surg Adjuvant Breast & Bowel Project, Ctr Biostat, Pittsburgh, PA 15212 USA. RP Wolmark, N (reprint author), Natl Surg Adjuvant Breast & Bowel Project, Allegheny Ctr 4, Operat Ctr, 5th Floor,320 E North Ave, Pittsburgh, PA 15212 USA. FU NCI NIH HHS [NCI-U10-CA-37377, NCI-U10-CA-12027, NCI-U10-CA-39086] NR 21 TC 346 Z9 355 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1999 VL 17 IS 5 BP 1349 EP 1355 PG 7 WC Oncology SC Oncology GA 195TH UT WOS:000080267900005 PM 10334518 ER PT J AU Cortazar, P Johnson, BE AF Cortazar, P Johnson, BE TI Review of the efficacy of individualized chemotherapy selected by in vitro drug sensitivity testing for patients with cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID CELL LUNG-CANCER; PROSPECTIVE CLINICAL-TRIAL; METASTATIC BREAST-CANCER; SUBRENAL CAPSULE ASSAY; TUMOR STEM-CELLS; PHASE-II TRIAL; OVARIAN-CANCER; ANTHRACYCLINE-RESISTANT; COLORIMETRIC ASSAY; MTT ASSAY AB Purpose: The purpose of this study is to review the potential efficacy of individualized chemotherapy selected by in vitro drug sensitivity testing (DST) compared with empiric regimens for patients with cancer. Methods: MEDLINE and CANCERLIT were searched for articles published tin English) about prospective clinical trials in which patients were treated with chemotherapy that was selected with the use of in vitro DST. Results: We identified 12 prospective studies that examined the benefit of chemotherapy selected by DST. Five hundred six patients (33%) were treated with chemotherapy that was selected with the use of in vitro DST. The mean response rate for patients treated with in vitro-selected therapy was 27% (range, 10% to 100%; 12 studies) compared with 18% (range, 0% to 100%; n = 7 studies) for patients treated with empiric therapy Five studies (only one randomized) evaluated the impact of chemotherapy selected by in vitro DST on patient survival. Three studies showed that survival was 1 to 4 months longer for the 238 patients treated with empiric chemotherapy compared with that of the 65 patients treated with chemotherapy that wets selected by in vitro testing. Two nonrandomized studies showed that survival wets 4 or 19 months longer for 27 patients treated with chemotherapy selected by in vitro testing compared with that of 80 patients who were treated with empiric chemotherapy. Conclusion: Only one third of patients entered in prospective trials of in vitro DST were actually treated with an in vitro best regimen. The response rates seem to be better with in vitro selected chemotherapy regimens than with empiric regimens, but the impact on survival has not been adequately addressed. J Clin Oncol 17:1625-1631. (C) 1999 by American Society of Clinical Oncology. C1 NCI, Lung Canc Biol Sect, Med Branch, USN,Div Clin Sci, Bethesda, MD 20892 USA. RP Johnson, BE (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 44 Binney St, Boston, MA 02115 USA. NR 41 TC 71 Z9 72 U1 1 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1999 VL 17 IS 5 BP 1625 EP 1631 PG 7 WC Oncology SC Oncology GA 195TH UT WOS:000080267900039 PM 10334552 ER PT J AU Fisher, B AF Fisher, B TI National surgical adjuvant breast and bowel project breast cancer prevention trial: A reflective commentary SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article C1 Allegheny Univ Hlth Sci, Natl Surg Adjuvant Breast & Bowel Project, Operat Ctr, Pittsburgh, PA 15212 USA. Allegheny Univ Hlth Sci, Natl Surg Adjuvant Breast & Bowel Project, Ctr Stat, Pittsburgh, PA 15212 USA. RP Fisher, B (reprint author), Allegheny Univ Hlth Sci, Natl Surg Adjuvant Breast & Bowel Project, Operat Ctr, 4 Allegheny Ctr,Suite 602, Pittsburgh, PA 15212 USA. FU NCI NIH HHS [U10-CA37377, U10-CA69974] NR 3 TC 30 Z9 31 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1999 VL 17 IS 5 BP 1632 EP 1639 PG 8 WC Oncology SC Oncology GA 195TH UT WOS:000080267900040 PM 10334553 ER PT J AU Battjes, RJ Onken, LS Delany, PJ AF Battjes, RJ Onken, LS Delany, PJ TI Drug abuse treatment entry and engagement: Report of a meeting on treatment readiness SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article ID METHADONE-MAINTENANCE; INTEGRATIVE MODEL; FOLLOW-UP; AIDS; DETOXIFICATION; RETENTION; PROGRAM; USERS AB Although the effectiveness of drug abuse treatment has been demonstrated repeatedly, many drug abusers do not enter treatment, many who do enter leave prematurely, and relapse following treatment is common. To further research treatment entry and engagement, the National institute on Drug Abuse convened scientists representing diverse research traditions in December 1996. This article summarizes meeting presentations and recommendations. Presentations focused on treatment readiness/motivation for change, ethnographic reports of drug abusers' perceptions of and altitudes toward treatment, and reports on alternative treatments for high-risk drug abusers. Recommendations focused on the potential contribution of qualitative research, integration of qualitative and quantitative research approaches, development of flexible treatment approaches that are cognizant of patients' life circumstances, and services research to improve the organization and delivery of drug abuse treatment. (C) 1999 John Wiley & Sons, Inc. C1 NIDA, NIH, Bethesda, MD 20892 USA. RP Battjes, RJ (reprint author), NIDA, NIH, 6001 Execut Blvd,Room 4234,MSC 9557, Bethesda, MD 20892 USA. NR 27 TC 47 Z9 47 U1 1 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD MAY PY 1999 VL 55 IS 5 BP 643 EP 657 DI 10.1002/(SICI)1097-4679(199905)55:5<643::AID-JCLP11>3.0.CO;2-S PG 15 WC Psychology, Clinical SC Psychology GA 190JN UT WOS:000079959500011 PM 10392794 ER PT J AU Eliav, E Benoliel, R Gracely, RH AF Eliav, E Benoliel, R Gracely, RH TI Sensory changes following lower third molars extraction. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Hadassah Sch Dent Med, Dept Oral Diagnosis Oral Med & Radiol, Jerusalem, Israel. NIDR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAY PY 1999 VL 78 IS 5 BP 1098 EP 1098 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 196PK UT WOS:000080316601214 ER PT J AU Shibaki, A AF Shibaki, A TI Fc epsilon RI on dendritic cells: a receptor, which links IgE mediated allergic reaction and T cell mediated cellular response SO JOURNAL OF DERMATOLOGICAL SCIENCE LA English DT Review DE IgE; Fc epsilon RI; Langerhans cells; dendritic cells; atopic dermatitis ID EPIDERMAL LANGERHANS CELLS; HIGH-AFFINITY RECEPTOR; IMMUNOGLOBULIN-E RECEPTOR; ANTIGEN-PRESENTING CELLS; ATOPIC-DERMATITIS; BETA-SUBUNIT; LESIONAL SKIN; MAST-CELLS; B-CELLS; TYROSINE PHOSPHORYLATION AB Dendritic cells (DC) are bone marrow derived cells with strong antigen presenting capacity and can induce primary immune responses by activating naive T cells. Cells of this lineage are called as professional antigen presenting cells (APC), because of their primary function as APC. Since the demonstration of IgE bound epidermal Langerhans cells (LC) in atopic dermatitis (AD) patients, a role of IgE bearing DC as a regulator of IgE mediated allergic reactions is emphasized. Indeed, IgE molecules on DC are functional. DC can take up, process and present IgE bound antigens to T cells more efficiently by means of their surface IgE receptor, Fc epsilon RI. In addition to its role as an antigen focusing molecule, DC Fc epsilon RI may have another function to induce co-stimulatory signals to T cells, by which Th2 type T cell activation is preferentially induced. Thus, this receptor could serve as an amplifying factor for T cell mediated allergic reactions. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Hokkaido Univ, Sch Med, Dept Dermatol, Sapporo, Hokkaido 060, Japan. RP Shibaki, A (reprint author), NCI, Dermatol Branch, NIH, Bldg 10,Rm 12N250,10 Ctr Dr, Bethesda, MD 20892 USA. NR 90 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0923-1811 J9 J DERMATOL SCI JI J. Dermatol. Sci. PD MAY PY 1999 VL 20 IS 1 BP 29 EP 38 DI 10.1016/S0923-1811(99)00003-1 PG 10 WC Dermatology SC Dermatology GA 192FZ UT WOS:000080069000004 ER PT J AU Ohta, N Tsai, JY Secchi, EF Kador, PF Sato, S AF Ohta, N Tsai, JY Secchi, EF Kador, PF Sato, S TI Neutrophils in galactose-fed dogs: Suppressed apoptosis and increased adhesion to retinal capillary endothelial cells SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article ID ALDOSE REDUCTASE INHIBITORS; NO-REFLOW PHENOMENON; PROTEIN-KINASE-C; DIABETIC-RETINOPATHY; POLYMORPHONUCLEAR LEUKOCYTES; HEMORRHAGIC-SHOCK; SKELETAL-MUSCLE; ACTIVATION; MICROCIRCULATION; PREVENTION AB Dogs fed a diet containing 30% galactose develop diabetes-like retinal capillary changes. As retinal capillary occlusion is commonly observed in diabetic retinopathy, neutrophil apoptosis and the interaction of neutrophils with retinal capillary endothelial cells were investigated. Neutrophils were isolated with Ficoll-Hypaque centrifugation from dogs fed a 30% galactose diet and dogs fed a normal, control diet containing 30% non-nutrient filler. Apoptosis of neutrophils was microscopically examined after incubation at 37 degrees C for 3 hours with either 100 U/mL tumor necrosis factor alpha (TNF-alpha), 2 mu g/mL cycloheximide or 50 ng/mL phorbol 12-myristate 13-acetate (PMA). Neutrophil adhesion to dog retinal capillary endothelial cells was examined by counting the cells attached to the surface of endothelial cells after the incubation in the presence of either 100 U/mL TNF-alpha or 5 mu g/mL lipopolysaccharides (LPS) at 37 degrees C for 3 hours. With all three stimulants TNF-alpha, cycloheximide and PMA, the rate of apoptosis was significantly lower for neutrophils isolated from galactose-fed dogs compared to control dogs fed a normal diet. Preincubation of neutrophils from control dogs in medium containing 30% galactose for 3 hours did not affect the rate of apoptosis. Neutrophil adhesion to retinal capillary endothelial cells induced by incubation in the presence of either 100 U/mL TNF-alpha or 5 mu g/ml LPS was significantly higher with neutrophils isolated from galactose-fed dogs than those from control dogs. The data indicate that long-term galactose feeding is essential with development of various neutrophil dysfunctions. These neutrophil changes may contribute to the development of retinal microangiopathy associated with diabetes and galactosemia. (C) 1999 Elsevier Science Inc. C1 NEI, Lab Ocular Therapeut, NIH, Bethesda, MD 20892 USA. RP Sato, S (reprint author), NEI, Lab Ocular Therapeut, NIH, Bldg 10,Rm 10B09,10 Ctr Dr,MCS 1850, Bethesda, MD 20892 USA. NR 42 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD MAY-JUN PY 1999 VL 13 IS 3 BP 151 EP 158 DI 10.1016/S1056-8727(99)00040-9 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 241AC UT WOS:000082858200005 PM 10509875 ER PT J AU Guembe, L Villaro, AC Treston, AM AF Guembe, L Villaro, AC Treston, AM TI Immunocytochemical mapping of the amidating enzyme PAM in the developing and adult mouse lung SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE mouse lung; development; amidation; PAM; PHM; PAL; Clara cells; smooth muscle; macrophages ID PEPTIDE ALPHA-AMIDATION; MONOOXYGENASE PAM; MESSENGER-RNA; INSITU HYBRIDIZATION; AIRWAY EPITHELIUM; RAT-HEART; EXPRESSION; PITUITARY; TISSUE; PANCREAS AB The enzyme PAM is required for activation of many peptide hormones. In adult mouse lung, immunostaining for PAM was located in Clara cells, which constitute most of the epithelial cells of the mouse bronchial/bronchiolar tree. Immunoreactivity appeared for the first time in the epithelium on gestational Day 16, being slight and mostly restricted to the apical cytoplasm. As the lung developed, the labeling became gradually stronger and extended throughout the cell. Smooth muscle of airways and blood vessels, and some parenchymal cells, probably macrophages, also showed PAM immunoreactivity. Of the two enzymatically active domains of PAM, only PHM and not PAL immunoreactivity was found at all stages studied. The early appearance of PAM in developing mouse lung, as well as its presence in a variety of tissues, probably indicates a complex role of this enzyme in pulmonary development and function. C1 Univ Navarra, Dept Cytol & Histol, E-31080 Pamplona, Spain. NCI, Biomarkers & Prevent Res Branch, Div Canc Prevent & Control, NIH, Rockville, MD USA. RP Guembe, L (reprint author), Univ Navarra, Dept Cytol & Histol, E-31080 Pamplona, Spain. NR 53 TC 3 Z9 3 U1 0 U2 1 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD MAY PY 1999 VL 47 IS 5 BP 623 EP 636 PG 14 WC Cell Biology SC Cell Biology GA 197RU UT WOS:000080380100005 PM 10219055 ER PT J AU Arya, SK Ginsberg, CC Davis-Warren, A D'Costa, J AF Arya, SK Ginsberg, CC Davis-Warren, A D'Costa, J TI In vitro phenotype of SDF1 gene mutant that delays the onset of human immunodeficiency virus disease in vivo SO JOURNAL OF HUMAN VIROLOGY LA English DT Article DE SDF1; polymorphism; gene expression; human immunodeficiency virus load; disease progression ID CHEMOKINE RECEPTORS; HIV-1 INFECTION; PROGRESSION; TYPE-2; CCR5; THERAPY; PATHOGENESIS; INHIBITION; EXPRESSION; VARIANTS AB Objective: Inheritance of a mutant allele of the SDF1 gene delays the onset of human immunodeficiency virus type 1 (HIV-1) disease. Because the mutation lies in the 3' umtranslated region of the gene, it was suggested that this mutation may upregulate transcription of the gene, resulting in more abundant SDF1, which in turn inhibits T-tropic HIV-1 and delays disease onset. This implies that this segment of SDF1 gene contains a negative regulatory element. We directly tested this hypothesis in vitro. Study Design/Methods: We cloned the wild-type and the mutant SDF1 gene in an HIV-2 gene transfer vector as well as in a baculovirus expression vector. We expressed the cloned genes in human and insect cells in culture and analyzed the abundance of SDF1 RNA by hybridization and protein using antiviral assays. Results: The abundance of SDF1 RNA synthesized by the mutant clone with the mutation in the 3' untranslated region was no different from that synthesized by the wild-type clone in cultured cells. This was the case for both the HIV-2 long terminal repeat (LTR)-directed expression in human cells and baculovirus promoter-directed expression in insect cells. Both clones apparently synthesized SDF1 with equivalent biologic activity. Similar results were obtained for a mutant with the deletion of a GC-rich segment in the 5' untranslated region. Conclusions: Mutation of the 3' untranslated exon did not affect SDF1 RNA synthesis in vitro. It also did not appear to affect translation of SDF1 RNA. A similar mutational analysis of the 5' noncoding exon suggested that this region also did not regulate SDF1 expression. C1 NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. RP Arya, SK (reprint author), NCI, Basic Res Lab, NIH, Bldg 37,Room 6C21, Bethesda, MD 20892 USA. NR 20 TC 27 Z9 28 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1090-9508 J9 J HUMAN VIROL JI J. Human Virol. PD MAY-JUN PY 1999 VL 2 IS 3 BP 133 EP 138 PG 6 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA 245AY UT WOS:000083085100002 PM 10413364 ER PT J AU Li, QS Eiden, LE Cavert, W Reinhat, TA Rausch, DM Murray, EA Weihe, E Haase, AT AF Li, QS Eiden, LE Cavert, W Reinhat, TA Rausch, DM Murray, EA Weihe, E Haase, AT TI Increased expression of nitric oxide synthase and dendritic injury in simian immunodeficiency virus encephalitis SO JOURNAL OF HUMAN VIROLOGY LA English DT Article DE nitric oxide; encephalitis; simian immunodeficiency virus (SIV) ID INFECTED RHESUS-MONKEYS; CENTRAL-NERVOUS-SYSTEM; SIV INFECTION; AIDS; DEMENTIA; BRAINS; QUANTITATION; MACROPHAGES; SPECTRUM AB Objectives: Widespread dendritic injury may be one mechanism involved in the neurologic impairment that occurs in HIV-1 infection. The objectives of this study were to quantitate the extent of dendritic injury in a primate model of central nervous system (CNS) infection, investigate the role of nitric oxide (NO) as a mediator of neuropathologic changes, and evaluate the relation of these changes to cognitive and motor function. Study Design/Methods: Cognitive and motor function was assessed in rhesus macaque monkeys infected with simian immunodeficiency virus (SN). In situ hybridization, immunohistochemistry, and quantitative image analysis were employed to assess the relations among productive infection, NO synthase (iNOS), and dendritic injury. Results: Productive infection of cells of the macrophage lineage in CNS is associated with inflammation, increased expression of iNOS, and dendritic injury. The tests of cognitive and motor function employed were abnormal in both animals that had evidence of productive infection and those that did not. Conclusions: Increased NO accompanying productive infection and encephalitis may be one cause of neuronal injury in lentivirus infections of the CNS. Extension of tests of cognitive and motor function to late-stage AIDS in rhesus monkeys is needed to assess the potential role of NO-induced dendritic damage in lentiviral encephalopathy/AIDS dementia complex. C1 Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA. NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Microbiol, Pittsburgh, PA USA. NIMH, Neuropsychol Lab, Sect Neurobiol Learning & Memory, Bethesda, MD 20892 USA. Univ Marburg, Inst Anat & Cell Biol, Marburg, Germany. RP Haase, AT (reprint author), Univ Minnesota, Dept Microbiol, Box 196 Mayo,420 Delaware St SE, Minneapolis, MN 55455 USA. OI Eiden, Lee/0000-0001-7524-944X; Murray, Elisabeth/0000-0003-1450-1642 FU NIAID NIH HHS [AI 28246, AI 38565] NR 29 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1090-9508 J9 J HUMAN VIROL JI J. Human Virol. PD MAY-JUN PY 1999 VL 2 IS 3 BP 139 EP 145 PG 7 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA 245AY UT WOS:000083085100003 PM 10413365 ER PT J AU Bennett, EM Bennink, JR Yewdell, JW Brodsky, FM AF Bennett, EM Bennink, JR Yewdell, JW Brodsky, FM TI Cutting edge: Adenovirus E19 has two mechanisms for affecting class I MHC expression SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL-SURFACE EXPRESSION; ENDOPLASMIC-RETICULUM; ANTIGEN PRESENTATION; E3/19K PROTEIN; GLYCOPROTEIN; MOLECULES; TAPASIN; HLA; TAP; CALRETICULIN AB Viral strategies for immune evasion include inhibition of various steps in the class I MHC assembly pathway. Here,,ve demonstrate that adenovirus produces one gene product with a dual function in this regard. It is well established that adenovirus E19 binds class I molecules and retains them in the endoplasmic reticulum (ER), However, E19 also delays the expression of class I alleles to which it cannot tightly bind. Here, we show that E19 binds TAP and acts as a tapasin inhibitor, preventing class I/TAP association. Delta E19, an E19 mutant lacking the ER retention signal, delays maturation of class I molecules, indicating that E19's inhibition of class I/TAP interaction is sufficient to delay class I expression. These data identify tapasin inhibition as a novel mechanism of viral immune evasion and suggest that, through this secondary mechanism, adenovirus can affect Ag presentation by MHC alleles that it can only weakly affect by direct retention. C1 Univ Calif San Francisco, George Williams Hooper Fdn, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RP Brodsky, FM (reprint author), Univ Calif San Francisco, George Williams Hooper Fdn, Dept Microbiol & Immunol, Box 0552, San Francisco, CA 94143 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 FU NIGMS NIH HHS [GM07175-23, GM38093, GM57657] NR 26 TC 137 Z9 141 U1 0 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1999 VL 162 IS 9 BP 5049 EP 5052 PG 4 WC Immunology SC Immunology GA 189EZ UT WOS:000079892600005 PM 10227971 ER PT J AU Hoshino, T Wiltrout, RH Young, HA AF Hoshino, T Wiltrout, RH Young, HA TI IL-18 is a potent coinducer of IL-13 in NK and T cells: A new potential role for IL-18 in modulating the immune response SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERFERON-GAMMA PRODUCTION; NATURAL-KILLER-CELLS; IFN-GAMMA; CYTOKINE PRODUCTION; B-CELLS; DIFFERENTIAL REGULATION; MACROPHAGE ACTIVATION; HELPER CELL; IN-VIVO; RECEPTOR AB IL-13 and IL-4 have similar biological activities and are characteristic of cytokines expressed by Th2 cells. In contrast, IL-12 and IL-18 have been shown to be strong cofactors for Th1 cell development. In this study, we found strong induction of IL-13 mRNA and protein by IL-2 + IL-18 in NK and T cells, In contrast, IL-12 did not enhance the IL-13 production induced by IL-2 alone. Moreover, IL-13 mRNA and protein expression induced by IL-2 + IL-18 in purified NK and T cells obtained from IFN-gamma knockout (-/-) mice were greater than seen in purified cells from normal controls. In contrast, IL-IB production induced by IL-2 and/or IL-12 was not significantly different in IFN-gamma (-/-) mice and normal controls, These results suggest IL-13 expression induced by IL-2 + IL-18 may. be regulated by IFN-gamma in vivo, while IL-IO expression may be IFN-gamma-independent. Thus, depending upon the cell type. IL-18 may act as a strong coinducer of Th1 or Th2 cytokines. Our findings suggest that IL-12 and IL-18 have different roles in the regulation of gene expression in NK and T cells. C1 NCI, Frederick Canc Res & Dev Ctr, Expt Immunol Lab, Div Basic Sci, Frederick, MD 21702 USA. RP Young, HA (reprint author), NCI, Frederick Canc Res & Dev Ctr, Expt Immunol Lab, Div Basic Sci, Bldg 560,Room 31-93, Frederick, MD 21702 USA. RI Young, Howard/A-6350-2008 OI Young, Howard/0000-0002-3118-5111 NR 40 TC 263 Z9 272 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1999 VL 162 IS 9 BP 5070 EP 5077 PG 8 WC Immunology SC Immunology GA 189EZ UT WOS:000079892600009 PM 10227975 ER PT J AU Galvin, JP Spaeny-Dekking, LHA Wang, B Seth, P Hack, CE Froelich, CJ AF Galvin, JP Spaeny-Dekking, LHA Wang, B Seth, P Hack, CE Froelich, CJ TI Apoptosis induced by granzyme B-glycosaminoglycan complexes: Implications for granule-mediated apoptosis in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOTOXIC LYMPHOCYTES; TARGET-CELLS; PROTEASES; DELIVERY; PERFORIN; PROTEOGLYCANS; ACTIVATION; ENTRY AB Lymphocyte granule-mediated apoptosis occurs by perforin-mediated intracellular delivery of granule-associated serine proteases (granzymes), A granule-associated proteoglycan, namely serglycin, that contains chondroitin ii-sulfate (CS) glycosaminoglycans is present in the granules of cytotoxic cells. Serglycin acts as scaffold for packaging the positively charged granzymes and probably chaperones the proteases secreted extracellularly. To learn how the interaction of granzyme B (GrB) with serglycin might influence the apoptotic potential of this proteases, we have evaluated a model system where desalted CS is combined with isolated human granzyme. CS-GrB complexes were very stable, remaining undissociated in salt concentrations upwards to 500 mM (pH 7.4), On the basis of a capture enzyme immunoassay that accurately detects GrB, equivalent amounts of active free and CS-GrB, delivered by perforin or adenovirus, efficiently induced apoptosis in Jurkat cells and produced a similar time-dependent increase in caspase-3-like activity. CS-GrB processed isolated caspases-3 and -7 less efficiently than free granzyme, However, when added to cytosolic extracts, rates of processing were nearly equivalent for the two forms, suggesting cationic GrB mag nonspecifically bind cytosolic proteins, leading to reduce proteolytic activity, Finally, GrB was found to be exocytosed from lymphocyte-activated killer cells as a neutral, high macromolecular weight complex, which possessed apoptotic activity. Collectively, the results indicate that neutral, high m.w. GrB has the capacity to induce cell death and will be useful to study the mechanism of cytotoxic cell-mediated apoptosis in vitro. C1 Northwestern Univ, Evanston NW Healthcare Res Inst, Evanston, IL 60201 USA. Netherlands Red Cross, Blood Transfus Serv, Cent Lab, Amsterdam, Netherlands. Univ Amsterdam, Clin & Expt Immunol Lab, Amsterdam, Netherlands. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Froelich, CJ (reprint author), Evanston Hosp, Dept Res, WH Bldg,Room B643,2650 Ridge Ave, Evanston, IL 60201 USA. RI Galvin, John/D-2803-2012 NR 26 TC 43 Z9 44 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 MAY 1 PY 1999 VL 162 IS 9 BP 5345 EP 5350 PG 6 WC Immunology SC Immunology GA 189EZ UT WOS:000079892600044 PM 10228010 ER PT J AU Hausmann, S Biddison, WE Smith, KJ Ding, YH Garboczi, DN Utz, U Wiley, DC Wucherpfennig, KW AF Hausmann, S Biddison, WE Smith, KJ Ding, YH Garboczi, DN Utz, U Wiley, DC Wucherpfennig, KW TI Peptide recognition by two HLA-A2/Tax(11-19)-specific T cell clones in relationship to their MHC/peptide/TCR crystal structures SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOTROPIC VIRUS; RECEPTOR; ANTIGEN; TCR; BINDING; MOLECULES; COMPLEX; DISEASE; LIGANDS; HLA-A2 AB The crystal structures of two human TCRs specific for a HTLV-I Tax peptide bound to HLA-A2 were recently determined, for the first time allowing a functional comparison of TCRs for which the MHC/peptide/TCR structures are known. Extensive amino acid substitutions show that the native Tax residues are optimal at each peptide position. A prominent feature of the TCR contact surface is a deep pocket that accommodates a tyrosine at position 5 of the peptide, For one of these TCRs, this pocket is highly specific for aromatic residues, In the other TCR structure, this pocket is larger, allowing many different residues to be accommodated. The CTL clones also show major differences in the specificity for several other peptide residues, including side chains that are not directly contacted by the TCR Despite the specificity of these clones, peptides that are distinct at five or six positions from Tax(11-19) induce CTL activity, indicating that substantial changes of the peptide surface are tolerated. Human peptides with limited sequence homology to Tax(11-19) represent partial TCR agonists for these CTL clones. The distinct functional properties of these CTL clones highlight structural features that determine TCR specificity and cross-reactivity for MHC-bound peptides. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NINDS, Mol Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Childrens Hosp, Howard Hughes Med Inst, Mol Med Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Howard Hughes Med Inst, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. NIAID, Struct Biol Sect, NIH, Rockville, MD 20852 USA. Inst Rech Clin Montreal, Immunol Lab, Montreal, PQ H2W 1R7, Canada. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI42316]; NICHD NIH HHS [HD-17461] NR 30 TC 64 Z9 64 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 MAY 1 PY 1999 VL 162 IS 9 BP 5389 EP 5397 PG 9 WC Immunology SC Immunology GA 189EZ UT WOS:000079892600050 PM 10228016 ER PT J AU Yamaguchi, M Sayama, K Yano, K Lantz, CS Noben-Trauth, N Ra, C Costa, JJ Galli, SJ AF Yamaguchi, M Sayama, K Yano, K Lantz, CS Noben-Trauth, N Ra, C Costa, JJ Galli, SJ TI IgE enhances Fc epsilon receptor I expression and IgE-dependent release of histamine and lipid mediators from human umbilical cord blood-derived mast cells: Synergistic effect of IL-4 and IgE on human mast cell Fc epsilon receptor I expression and mediator release SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; HUMAN BASOPHILS; RI EXPRESSION; B-CELLS; PASSIVE SENSITIZATION; SERUM IGE; VIVO; BINDING; ANTIBODY; DEGRANULATION AB We investigated the effects of IgE versus IL-4 on Fc epsilon RI surface expression in differentiated human mast cells derived in vitro from umbilical cord blood mononuclear cells, We found that IgE (at 5 mu g/ml) much more strikingly enhanced surface expression of FceRI than did IL-4 (at 0.1-100 ng/ml); similar results were also obtained with differentiated mouse mast cells, However, IL-4 acted synergistically with IgE to enhance FceRI expression in these umbilical cord blood-derived human mast cells, as well as in mouse peritoneal mast cells derived from IL-4(-/-) or IL-4(+/+) mice, We also found that: 1) IgE-dependent enhancement of FceRI expression was associated with a significantly enhanced ability of these human mast cells to secrete histamine, PGD,, and leukotriene C-4 upon subsequent passive sensitization with IgE and challenge with anti-IgE; 2) preincubation with IL-4 enhanced IgE-dependent mediator secretion in these cells even in the absence of significant effects on FceRI surface expression; 3) when used together with IgE, IL-3 enhanced IgE-dependent mediator secretion in human mast cells to levels greater than those observed in cells that had been preincubated with IgE alone; and 4) batches of human mast cells generated in vitro from umbilical cord blood cells derived from different donors exhibited differences in the magnitude and pattern of histamine and lipid mediator release in response to anti-IgE challenge, both under baseline conditions and after preincubation with IgE and/or IL-4. C1 Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. NIAID, Immunol Lab, NIH, Rockville, MD 20852 USA. Juntendo Univ, Sch Med, Dept Immunol, Tokyo 113, Japan. RP Galli, SJ (reprint author), Stanford Univ, Med Ctr, Dept Pathol, 300 Pasteur Dr, Stanford, CA 94305 USA. FU NCI NIH HHS [CA/AI-72074]; NHLBI NIH HHS [P50 HL-56383]; NIAID NIH HHS [AI/CA-23900] NR 40 TC 187 Z9 193 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 MAY 1 PY 1999 VL 162 IS 9 BP 5455 EP 5465 PG 11 WC Immunology SC Immunology GA 189EZ UT WOS:000079892600059 PM 10228025 ER PT J AU Desai, SB Libutti, SK AF Desai, SB Libutti, SK TI Tumor angiogenesis and endothelial cell modulatory factors SO JOURNAL OF IMMUNOTHERAPY LA English DT Review DE tumor angiogenesis; endothelial cells; neovasculature ID FIBROBLAST GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; NECROSIS-FACTOR-ALPHA; RECEPTOR TYROSINE KINASE; FACTOR THYMIDINE PHOSPHORYLASE; INTERFERON-INDUCIBLE PROTEIN-10; ADHESION MOLECULE-1 EXPRESSION; SMOOTH-MUSCLE CELLS; EXTRINSIC-PATHWAY ACTIVATION; INTESTINAL EPITHELIAL-CELLS AB Angiogenesis is the ability of preexisting vasculature to send out capillary sprouts leading to the formation of new vasculature. It is now a well-accepted idea that progression of solid tumors is intrinsically dependent on angiogenesis for growth of the primary tumor and metastatic lesions. Investigations into tumor angiogenesis have focused on inhibition of tumor neovasculature as yet another possible mechanism for impairing tumor progression. Numerous studies have characterized cellular and molecular factors important to vascular formation and development and have led to the identification and understanding of requisite interactions between endothelium, angiogenic cytokines, and the supporting matrix. These studies have also led to the identification of cytokines involved in the proteolytic disruption of the basement membrane, the migration of endothelial cells, and the proliferation and formation of neoendothelium into functional vasculature. As therapies based on antiangiogenic strategies continue to evolve and clinical trials are conducted, these agents may become an important part of the arsenal against tumor proliferation, especially given their favorable toxicity profile. This review discusses the angiogenic cytokines which have been most intensely studied and the receptors they act upon. Additionally, we discuss select proteases and their importance in the development of neovasculature. A better understanding of these components will help in the development of novel therapeutic strategies. C1 NCI, Surg Metab Sect, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Libutti, SK (reprint author), NCI, Surg Metab Sect, Surg Branch, NIH, Bldg 10,Room 2B17, Bethesda, MD 20892 USA. NR 348 TC 36 Z9 39 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAY PY 1999 VL 22 IS 3 BP 186 EP 211 DI 10.1097/00002371-199905000-00002 PG 26 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 194DA UT WOS:000080175800002 PM 10335479 ER PT J AU Murakami, M Gurski, KJ Steller, MA AF Murakami, M Gurski, KJ Steller, MA TI Human papillomavirus vaccines for cervical cancer SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE human papillomavirus; vaccine; cervical cancer ID CYTOTOXIC T-LYMPHOCYTES; CLASS-II PRESENTATION; ANTIGEN PRESENTATION; ANTITUMOR IMMUNITY; DENDRITIC CELLS; CTL EPITOPES; E7 PROTEINS; TYPE-16 E7; HLA-A; VIRUS AB Cervical cancer is one of the most common causes of cancer-related death in women. As a result of several recent advances in molecular biology, the association between human papillomavirus (HPV) infection and cervical cancer has been firmly established, and the oncogenic potential of certain HPV types has been clearly demonstrated. Several lines of evidence suggest the importance of the host's immune response, especially cellular immune response, in the pathogenesis of HPV-associated cervical lesions. These observations form a compelling rationale for the development of vaccine therapy to combat HPV infection. Both prophylactic and therapeutic HPV vaccine strategies are being developed. Prophylactic strategies currently under investigation focus on the induction of effective humoral immune responses against subsequent HPV infection. In this respect, impressive immunoprophylactic effects have been demonstrated in animals using papillomavirus-like particles (VLPs). VLPs are antigenic and protective, but are devoid of any viral DNA that may be carcinogenic to the host. For treatment of existing HPV infection, techniques to improve cellular immunity by enhancing viral antigen recognition are being studied. For this purpose, the oncogenic proteins E6 and E7 of HPV-16 and -18 are the focus of current clinical trials for cervical cancer patients. The development of successful HPV-specific vaccines may offer an attractive alternative to existing screening and treatment programs for cervical cancer. C1 NCI, Gynecol Oncol Sect, Surg Branch, Div Clin Sci, Bethesda, MD 20892 USA. RP Steller, MA (reprint author), Brown Univ, Women & Infants Hosp, 1 Blackstone Pl,3rd Floor, Providence, RI 02905 USA. NR 60 TC 35 Z9 39 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAY PY 1999 VL 22 IS 3 BP 212 EP 218 DI 10.1097/00002371-199905000-00003 PG 7 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 194DA UT WOS:000080175800003 PM 10335480 ER PT J AU Kicklighter, EJ Lee, KH Barracchini, KC Bettinotti, M Norris, R Simonis, TB Stroncek, D Marincola, FM AF Kicklighter, EJ Lee, KH Barracchini, KC Bettinotti, M Norris, R Simonis, TB Stroncek, D Marincola, FM TI High-resolution HLA-A*0201 subtyping using directed heteroduplex analysis SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE HLA-A*0201; subtyping; directed heteroduplex analysis ID POLYMERASE CHAIN-REACTION; PEPTIDE-BASED IMMUNOTHERAPY; HLA-A2 SUBTYPES; ANTIGENS; INDUCTION; MOLECULES; PRODUCTS; ALLELES; BINDING; PCR AB HLA-A02* has become an important target for cytotoxic T lymphocyte-based immunotherapy reflecting the high prevalence of this allele in patient populations. There are at least 26 different A*02 alleles, and their subtype specificity has significant functional implications for T-cell-mediated recognition of immunologic targets. We have developed a novel method for HLA-A*02 allelic screening using directed heteroduplex analysis (DHDA). DNA samples from Epstein-Barr virus (EBV)-transformed B lymphoblastoid cell lines (EBV-B) representing 10 different HLA-A*02 alleles (0201, 0202, 0204, 0205, 0206, 0208, 0210, 0211, 0216, 0217) were prepared. In addition, DNA was prepared from 81 individuals representing a wide variety of A*02 subtypes previously determined by sequence specific primer (SSP) polymerase chain reaction (PCR) including individuals heterozygous for two A*02 specificities. Probes and samples were generated by PCR amplification using HLA-A*02 specific primers encompassing exons 2 and 3, where most of the functionally significant allelic polymorphism is clustered. DHDA was performed by generating heteroduplex molecules composed of a fluorescein-labeled allelic probe sequence and an unlabeled allelic PCR product. Gel retardation was consistent for allele-probe combinations. We were able to identify several A*02 alleles prepared from EBV-B cell lines that, when used as probes, had very impressive specificity and sensitivity. Combinations of two probes were identified (0205 + 0211 and 0208 + 0211) that allowed differentiation of A*0201 alleles from all other A*02 alleles tested. All samples typed by probe combinations had DHDA typing and SSP typing confirmed by DNA sequencing. This study expands the molecular typing repertoire available to the modern HLA laboratory, and shows that DHDA has significant promise as a reliable screening method for HLA A*02 subtyping. C1 NCI, Surg Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NCI, Ctr Clin, Dept Transfus Med, NIH, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NCI, Surg Branch, Div Clin Sci, NIH, Bldg 10,Room 2B56, Bethesda, MD 20892 USA. NR 26 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAY PY 1999 VL 22 IS 3 BP 219 EP 228 DI 10.1097/00002371-199905000-00004 PG 10 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 194DA UT WOS:000080175800004 PM 10335481 ER PT J AU Tan, D Matsumoto, A Conry-Cantilena, C Melpolder, JC Shih, JWK Leuther, M Hess, G Gibble, JW Ness, PM Alter, HJ AF Tan, D Matsumoto, A Conry-Cantilena, C Melpolder, JC Shih, JWK Leuther, M Hess, G Gibble, JW Ness, PM Alter, HJ TI Analysis of hepatitis G virus (HGV) RNA, antibody to HGV envelope protein, and risk factors for blood donors coinfected with HGV and hepatitis C virus SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Gastroenterological-Association / Digestive Disease Week CY MAY 16-20, 1998 CL NEW ORLEANS, LOUISIANA SP Amer Gastroenterol Assoc ID A-E HEPATITIS; GBV-C/HGV INFECTION; LIVER-DISEASE; CLINICAL IMPLICATIONS; TRANSMISSION; PREVALENCE; VIREMIA; HCV; GLYCOPROTEIN; ASSOCIATION AB Serologic, biochemical, and molecular analyses were used to study hepatitis G virus (HGV), antibody to the HGV envelope protein (anti-E2), risk factors, clinical significance, and the impact of HGV on coexistent hepatitis C virus (HCV), Among 329 donors with confirmed HCV infection, 12% were HGV RNA-positive and 44% were anti-E2-positive (total exposure, 56%), HGV RNA and anti-E2 were mutually exclusive except in 9 donors (1.5%); 8 of 9 subsequently lost HGV RNA but anti-E2 persisted. HGV had little impact on alanine aminotransferase, aspartate aminotransferase, or gamma-glutamyl transpeptidase in donors with HGV infection alone or those coinfected with HCV. A multivariate analysis showed that intravenous drug abuse was the leading risk factor for HGV transmission, followed by blood transfusion, snorting cocaine, imprisonment, and a history of sexually transmitted diseases. In summary, HGV and HCV infections were frequently associated and shared common parenteral risk factors; HGV did not appear to cause hepatitis or to worsen the course of coexistent hepatitis C. C1 NIH, Dept Transfus Med, Infect Dis Sect, Ctr Clin, Bethesda, MD 20892 USA. Greater Chesapeake & Potomac Reg Amer Res Cross, Baltimore, MD USA. Boehringer Mannheim GmbH, D-6800 Mannheim, Germany. RP Alter, HJ (reprint author), NIH, Dept Transfus Med, Infect Dis Sect, Ctr Clin, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 31 TC 22 Z9 22 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1999 VL 179 IS 5 BP 1055 EP 1061 DI 10.1086/314722 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 189TQ UT WOS:000079922600001 PM 10191204 ER PT J AU Lekstrom-Himes, JA Hohman, P Warren, T Wald, A Nam, JM Simonis, T Corey, L Straus, SE AF Lekstrom-Himes, JA Hohman, P Warren, T Wald, A Nam, JM Simonis, T Corey, L Straus, SE TI Association of major histocompatibility complex determinants with the development of symptomatic and asymptomatic genital herpes simplex virus type 2 infections SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 38th Interscience Conference on Antimicrobial Agents and Chemotherapy CY SEP 24-28, 1998 CL SAN DIEGO, CALIFORNIA ID NATURAL-KILLER-CELLS; ERYTHEMA MULTIFORME; T-CELL; IMMUNE-RESPONSE; ANTIBODY-TITERS; GLYCOPROTEIN-B; MEDIATED LYSIS; HLA ANTIGENS; CLASS-I; SUSCEPTIBILITY AB The clinical spectrum of herpes simplex virus (HSV) infections, ranging from asymptomatic to frequently distressing outbreaks, suggests that there may be immunologic determinants of disease severity that are associated with human leukocyte antigen (HLA) expression. A controlled, prospective study identified several major histocompatibility complex (MHC) class I and II antigens whose frequencies are associated with HSV-2 infection or with frequent symptomatic genital recurrences. Previous studies were hampered by the inability to serologically identify patients with asymptomatic HSV-2 infection. Clinical evaluation and Western blot assay were used to identify 3 subject cohorts: 1 with no prior HSV infections, 1 with HSV-2 antibodies but no recognized symptoms, and 1 with HSV-2 antibodies and frequent genital recurrences. Statistical comparisons of HLA frequencies among these cohorts showed associations of HLA-B27 and -Cw2 with symptomatic disease, Also, HLA-Cw4 was significantly associated with HSV-2 infection, These associations indicate that immunologic factors linked to the MHC influence the risk of HSV-2 infection and disease expression. C1 NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. Westover Hts Clin, Portland, OR USA. Univ Washington, Dept Lab Med, Program Infect Dis, Seattle, WA 98195 USA. Univ Washington, Dept Med, Program Infect Dis, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Straus, SE (reprint author), NIAID, Clin Invest Lab, NIH, Bldg 10,Room 11N-228,10 Ctr Dr, Bethesda, MD 20892 USA. RI Wald, Anna/B-6272-2012 OI Wald, Anna/0000-0003-3486-6438 NR 65 TC 39 Z9 40 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1999 VL 179 IS 5 BP 1077 EP 1085 DI 10.1086/314729 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 189TQ UT WOS:000079922600004 PM 10191207 ER PT J AU Suffredini, AF Hochstein, HD McMahon, FG AF Suffredini, AF Hochstein, HD McMahon, FG TI Dose-related inflammatory effects of intravenous endotoxin in humans: Evaluation of a new clinical lot of Escherichia coli O : 113 endotoxin SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TUMOR-NECROSIS-FACTOR AB The administration of reference endotoxin (Escherichia coli O:113, Lot EC-5) to humans has been an important means to study inflammation in vivo; however, the supply of Lot EC-5 is depleted. A new lot of reference endotoxin (Clinical Center reference endotoxin [CCRE]), derived from the original bulk material extracted from E. coli O:113, was processed. The effects of 0-, 1-, 2-, and 4-ng/kg doses of intravenous CCRE and EC-5 were studied in 20 male subjects. CCRE resulted in dose-related increases in symptoms, temperature (P = .016), total leukocyte count (P = .014), tumor necrosis factor-alpha (P = .004), interleukin (IL)-1 receptor antagonist (P = .004),IL-6 (P = .005), IL-8 (P = .011), cortisol (P < .05), and C-reactive protein (P = .04), These responses were attenuated (all P < .012) in subjects given Lot EC-5 (4 ng/kg) in comparison with those in subjects given CCRE, showing that, over several years, EC-5 had lost potency. Thus, in healthy subjects, the magnitude of exposure to CCRE results in a graded dose response of major components of innate immunity. C1 NIH, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. US FDA, Div Prod Qual Control, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Clin Res Ctr, New Orleans, LA USA. RP Suffredini, AF (reprint author), NIH, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bldg 10,Room 7D-43,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA. NR 14 TC 112 Z9 116 U1 2 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1999 VL 179 IS 5 BP 1278 EP 1282 DI 10.1086/314717 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 189TQ UT WOS:000079922600034 PM 10191237 ER PT J AU Kresina, TF Mathieson, B AF Kresina, TF Mathieson, B TI Human immunodeficiency virus type I infection, mucosal immunity, and pathogenesis and extramural research programs at the National Institutes of Health SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Meeting on HIV-1 Infection, Mucosal Immunity, and Pathogenesis CY SEP 11-13, 1997 CL BETHESDA, MARYLAND C1 NIDDK, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. NIH, Off AIDS Res, Bethesda, MD 20892 USA. RP Kresina, TF (reprint author), NIDDK, Div Digest Dis & Nutr, NIH, 45 Ctr Dr, Bethesda, MD 20892 USA. NR 4 TC 11 Z9 13 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1999 VL 179 SU 3 BP S392 EP S396 DI 10.1086/314815 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 190PP UT WOS:000079973300002 PM 10099104 ER PT J AU Kresina, TF AF Kresina, TF TI HIV-1 Infection, Mucosal Immunity & Pathogenesis - National Institutes of Health, Bethesda, Maryland - 11-13 September 1997 - Introduction SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material C1 NIDDKD, AIDS Program, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Kresina, TF (reprint author), NIDDKD, AIDS Program, Div Digest Dis & Nutr, NIH, 45 Ctr Dr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1999 VL 179 SU 3 BP S391 EP S391 DI 10.1086/314816 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 190PP UT WOS:000079973300001 ER PT J AU Wahl, SM Greenwell-Wild, T Peng, G Hale-Donze, H Orenstein, JM AF Wahl, SM Greenwell-Wild, T Peng, G Hale-Donze, H Orenstein, JM TI Co-infection with opportunistic pathogens promotes human immunodeficiency virus type 1 infection in macrophages SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Meeting on HIV-1 Infection, Mucosal Immunity, and Pathogenesis CY SEP 11-13, 1997 CL BETHESDA, MARYLAND ID NECROSIS FACTOR-ALPHA; HIV; REPLICATION; AIDS; EXPRESSION; SURVIVAL; DISEASE; CCR5 AB Human immunodeficiency virus type 1 (HIV-1) infection is dependent on susceptible host cells that express both CD4 and chemokine co-receptors. The co-receptor CCR5 is associated with primary infection by macrophage-tropic virus isolates, whereas CXCR4 is commonly associated with T cell- and dual-tropic viruses. Once infected, lymphocytes and macrophages may replicate HIV-1 or harbor latent virus, depending on environmental factors and cellular activation. Immune activation is often associated with viremia, which is consistent with enhanced infection and viral replication in activated cells harboring virus. In this regard, opportunistic infections activate the immune system with the detrimental sequelae of enhanced viral replication and viremia. Under these conditions, viral expansion extends beyond T cells to tissue macrophages, many of which are co-infected with opportunistic pathogens. The opportunistic infections promote macrophage susceptibility to HIV-1 through cytokine modulation and altered chemokine co-receptors, potential targets for intervention. C1 NIDR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. George Washington Univ, Dept Pathol, Washington, DC 20037 USA. RP Wahl, SM (reprint author), NIDR, Oral Infect & Immun Branch, NIH, 30 Convent Dr,MSC 4352, Bethesda, MD 20892 USA. FU NIDCR NIH HHS [DE-12585] NR 18 TC 37 Z9 37 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1999 VL 179 SU 3 BP S457 EP S460 DI 10.1086/314814 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 190PP UT WOS:000079973300017 PM 10099119 ER PT J AU Wahl, SM Smith, PD Janoff, EN AF Wahl, SM Smith, PD Janoff, EN TI Human immunodeficiency virus type 1 infection, mucosal immunity, and pathogenesis: Comments and conference summary SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Meeting on HIV-1 Infection, Mucosal Immunity, and Pathogenesis CY SEP 11-13, 1997 CL BETHESDA, MARYLAND C1 NIDR, Oral Infect & Immu Branch, NIH, Bethesda, MD 20892 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. VA Med Ctr, Birmingham, AL USA. Univ Minnesota, Minneapolis, MN USA. VA Med Ctr, Dept Med, Minneapolis, MN USA. RP Wahl, SM (reprint author), NIDR, Oral Infect & Immu Branch, NIH, Bldg 30,Room 328, Bethesda, MD 20892 USA. FU NIAID NIH HHS [AI-39445]; NIDCR NIH HHS [DE-42600]; NIDDK NIH HHS [DK-47322] NR 0 TC 3 Z9 6 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1999 VL 179 SU 3 BP S397 EP S400 DI 10.1086/314811 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 190PP UT WOS:000079973300003 PM 10099105 ER PT J AU Vasandani, VM Castelli, JC Hott, JS Saxena, S Mikulski, SM Youle, RJ AF Vasandani, VM Castelli, JC Hott, JS Saxena, S Mikulski, SM Youle, RJ TI Interferon enhances the activity of the anticancer ribonuclease, onconase SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID DOUBLE-STRANDED-RNA; TUMOR NECROSIS FACTOR; PPP(A2'P)NA-DEPENDENT RNASE; 2-5A-DEPENDENT RNASE; INHIBITION; CELLS; APOPTOSIS; PROTEIN; GROWTH; CYTOTOXICITY AB Interferons (IFN) are biologic agents involved in the antiviral response and the inhibition of tumor growth. Biochemical pathways of IFN action include the double-stranded RNA-activated oligoadenylate synthetase, RNase L, and double-stranded RNA-dependent protein kinase (PKR). Extracellular ribonucleases, especially onconase, also display antiviral and antitumor properties and involve degradation of RNA. We find that IFN increases the anticancer activity of onconase, These two agents work synergistically, and the effect is seen at the level of translation probably because of the degradation of tRNA. C1 NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Alfacell Corp, Bloomfield, NJ 07003 USA. RP Youle, RJ (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, Room 5D-37,10 Ctr Dr, Bethesda, MD 20892 USA. OI Saxena, Shailendra K/0000-0003-2856-4185 NR 36 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 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD MAY PY 1999 VL 19 IS 5 BP 447 EP 454 DI 10.1089/107999099313884 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 204UH UT WOS:000080782600003 PM 10386856 ER PT J AU Bielenberg, DR McCarty, MF Bucana, CD Yuspa, SH Morgan, D Arbeit, JM Ellis, LM Cleary, KR Fidler, IJ AF Bielenberg, DR McCarty, MF Bucana, CD Yuspa, SH Morgan, D Arbeit, JM Ellis, LM Cleary, KR Fidler, IJ TI Expression of interferon-beta is associated with growth arrest of murine and human epidermal cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE angiogenesis; differentiation ID CULTURED HUMAN KERATINOCYTES; RNA HYBRIDIZATION TECHNIQUE; HUMAN BLADDER-CARCINOMA; HUMAN-MELANOMA CELLS; CANCER METASTASIS; TRANSCRIPTIONAL INHIBITION; INTERLEUKIN-8 GENE; ALPHA-INTERFERONS; TRANSGENIC MICE; IFN-ALPHA AB The cytokine interferon-beta is a regulator of cell replication and function, including invasion and induction of angiogenesis. The goal of this study was to determine whether the expression of interferon-beta by cells in the epidermis correlated with terminal differentiation. In situ hybridization analysis and immunohistochemical staining of formalin-fixed, paraffin-embedded specimens of normal human and murine epidermis and human and murine skin tumors of epithelial origin revealed that only differentiated, nondividing cells of the epidermis expressed interferon-beta protein. Keratinocyte cultures established from the epidermis of 3 d old mice were maintained under conditions permitting continuous cell division or induction of differentiation. Continuously dividing cells did not produce interferon-beta whereas nondividing differentiated cells expressing keratin 1 did. Growth-arrested, undifferentiated keratinocytes also expressed interferon-beta protein. Neutralizing interferon-beta in the culture medium inhibited differentiation, but the addition of exogenous interferon-beta did not stimulate differentiation. These data indicate that interferon-beta is produced by growth-arrested, terminally differentiated keratinocytes. C1 Univ Texas, MD Anderson Cancer Ctr, Dept Canc Biol 173, Houston, TX 77030 USA. Univ Texas, MD Anderson Cancer Ctr, Dept Surg Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Cancer Ctr, Dept Pathol, Houston, TX 77030 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. Univ Calif San Francisco, Mt Zion Med Ctr, San Francisco, CA 94120 USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94120 USA. RP Fidler, IJ (reprint author), Univ Texas, MD Anderson Cancer Ctr, Dept Canc Biol 173, 1515 Holcombe Blvd, Houston, TX 77030 USA. FU NCI NIH HHS [CA16672, R35-CA42107] NR 65 TC 34 Z9 35 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 MAY PY 1999 VL 112 IS 5 BP 802 EP 809 DI 10.1046/j.1523-1747.1999.00566.x PG 8 WC Dermatology SC Dermatology GA 193EA UT WOS:000080121900019 PM 10233775 ER PT J AU Yamashiro, S Kamohara, H Yoshimura, T AF Yamashiro, S Kamohara, H Yoshimura, T TI MCP-1 is selectively expressed in the late phase by cytokine-stimulated human neutrophils: TNF-alpha plays a role in maximal MCP-1 mRNA expression SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE inflammation; chemokine; gene expression ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; TUMOR-NECROSIS-FACTOR; DELAYED-TYPE HYPERSENSITIVITY; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; INTERLEUKIN-1 RECEPTOR ANTAGONIST; PROLIFERATION POTENTIATING FACTOR; INDUCED RABBIT ARTHRITIS; PROGRAMMED CELL-DEATH; RED-BLOOD-CELLS; GENE-EXPRESSION AB Culture supernatants of phytohemagglutinin (PHA)-stimulated human peripheral blood mononuclear cells (PHA-sup) induced monocyte chemoattractant protein-1 (MCP-1) mRNA expression in human neutrophjls. MCP-1 mRNA was first detected by Northern analysis at 8 h, and the peak level was detected at 16 h and sustained until 72 h. Cycloheximide and genistein, but not pertussis toxin, inhibited the expression of MCP-1 mRNA, Reecombinant tumor necrosis factor a (TNF-cx) induced a low level MCP-1 mRNA accumulation in neutrophils, and addition of anti-TNF-a IgG blocked 30-70% of MCP-1 mRNA expression induced with PHA-sup, PHA-sup-stimulated PMN synthesized and secreted 3.1 +/- 1.3 ng/5 x 10(6) PMN MCP-1 within the first 24 h, Hybridization of P-32-labeled cDNA preparations to an array of human cytokine cDNAs further indicated that MCP-1 mRNA was selectively up-regulated in the late phase after stimulation with the PHA-sup. C1 NCI, Frederick Canc Res & Dev Ctr, Immunopathol Sect, Immunobiol Lab, Frederick, MD 21702 USA. RP Yoshimura, T (reprint author), NCI, Frederick Canc Res & Dev Ctr, Immunopathol Sect, Immunobiol Lab, Bldg 560,Rm 12-71, Frederick, MD 21702 USA. NR 54 TC 47 Z9 47 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAY PY 1999 VL 65 IS 5 BP 671 EP 679 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 194FR UT WOS:000080181900018 PM 10331497 ER PT J AU Chen, YD Dougherty, ER AF Chen, YD Dougherty, ER TI Markovian analysis of adaptive reconstructive multiparameter tau-openings SO JOURNAL OF MATHEMATICAL IMAGING AND VISION LA English DT Article DE adaptive filter; granulometry; Markov chain; mathematical morphology; opening ID FILTERS; REPRESENTATION AB A classical single-parameter tau-opening is a union of openings in which each structuring element is scaled by the same parameter. Multiparameter binary tau-openings generalize the model in two ways: first, parameters for each opening are individually defined; second, a structuring element can be parameterized relative to its overall shape, not merely sized. The reconstructive filter corresponding to an opening is defined by fully passing any grain (connected component) that is not fully eliminated by the opening and deleting all other grains. Adaptive design results from treating the parameter vector of a reconstructive multiparameter tau-opening as the state space of a Markov chain. Signal and noise are modeled as unions of randomly parameterized and randomly translated primary grains, and the parameter vector is transitioned depending on whether an observed grain is correctly or incorrectly passed. Various adaptive models are considered, transition probabilities are discussed, the state-probability increment equations are deduced from the appropriate Chapman-Kolmogorov equations, and convergence of the adaptation is characterized by the steady-state distribution relating to the Markov chain. C1 NIH, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. Texas A&M Univ, Dept Elect Engn, Texas Ctr Appl Technol, College Stn, TX 77843 USA. RP Chen, YD (reprint author), NIH, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0924-9907 J9 J MATH IMAGING VIS JI J. Math. Imaging Vis. PD MAY PY 1999 VL 10 IS 3 BP 253 EP 267 DI 10.1023/A:1008392507034 PG 15 WC Computer Science, Artificial Intelligence; Computer Science, Software Engineering; Mathematics, Applied SC Computer Science; Mathematics GA 198CW UT WOS:000080405400004 ER PT J AU Allanson, JE Greenberg, F Smith, ACM AF Allanson, JE Greenberg, F Smith, ACM TI The face of Smith-Magenis syndrome: a subjective and objective study SO JOURNAL OF MEDICAL GENETICS LA English DT Article DE Smith-Magenis syndrome; facial measurements AB We report a study of 55 subjects with Smith-Magenis syndrome, aged 9 months to 35 years. Each person has been evaluated with an assessment of "gestalt" and detailed facial measurement, using previously published methodology, with compilation of Z score pattern profiles. The facial phenotype of SMS is quite distinctive, even in the young child. The overall face shape is broad and square. The brews are heavy, with excessive lateral extension of the eyebrows. The eyes slant upwards and appear close set and deep set. The nose has a depressed root and, in the young child, a scooped bridge. With time, the bridge becomes more ski jump shaped. The height of the nose is markedly reduced while the nasal base is broad and the tip of the nose is full. The shape of the mouth and upper lip are most distinctive. The mouth is wide with full upper and lower lips. The central portion of the upper lip is fleshy and everted with bulky philtral pillars, producing a tented appearance that, in profile, is striking. With age, mandibular growth is greater than average and exceeds that of the maxilla. This leads to increased jaw width and protrusion and marked midface hypoplasia. Craniofacial pattern analysis supports these subjective impressions. After mid-childhood, mandibular dimensions consistently exceed their maxillary counterparts. Craniofacial widths are greater than corresponding depths and heights. Nasal height is reduced while nasal width is increased. There is mild brachycephaly. The most marked age related changes are increased width of the nose and lower face (mandibular width) with reduction in nasal height and midfacial depth. C1 Childrens Hosp Eastern Ontario, Dept Genet, Ottawa, ON K1H 8L1, Canada. Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. RP Allanson, JE (reprint author), Childrens Hosp Eastern Ontario, Dept Genet, 401 Smyth Rd, Ottawa, ON K1H 8L1, Canada. NR 11 TC 64 Z9 65 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD MAY PY 1999 VL 36 IS 5 BP 394 EP 397 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 196CD UT WOS:000080290700009 PM 10353786 ER PT J AU Slavotinek, A Rosenberg, M Knight, S Gaunt, L Fergusson, W Killoran, C Clayton-Smith, J Kingston, H Campbell, RHA Flint, J Donnai, D Biesecker, L AF Slavotinek, A Rosenberg, M Knight, S Gaunt, L Fergusson, W Killoran, C Clayton-Smith, J Kingston, H Campbell, RHA Flint, J Donnai, D Biesecker, L TI Screening for submicroscopic chromosome rearrangements in children with idiopathic mental retardation using microsatellite markers for the chromosome telomeres SO JOURNAL OF MEDICAL GENETICS LA English DT Article DE idiopathic mental retardation; submicroscopic chromosome rearrangement; chromosome telomeres; 1p monosomy ID WOLF-HIRSCHHORN SYNDROME; MOLECULAR CHARACTERIZATION; INTERSTITIAL DELETIONS; CRYPTIC TRANSLOCATION; INSITU HYBRIDIZATION; TERMINAL DELETIONS; PARTIAL MONOSOMY; LONG ARM; IDENTIFICATION; MICRODELETION AB Recently much attention has been given to the detection of submicroscopic chromosome rearrangements in patients with idiopathic mental retardation. We have screened 27 subjects with mental retardation and dysmorphic features for such rearrangements using a genetic marker panel screening. The screening was a pilot project using markers from the subtelomeric regions of all 41 chromosome arms. The markers were informative for monosomy in both parents at 366/902 loci (40.6%, 95% confidence interval 37.0-44.2%) in the 22 families where DNA was available from both parents. In two of the 27 subjects, submicroscopic chromosomal aberrations were detected. The first patient had a 5-6 Mb deletion of chromosome 18q and the second patient had a 4 Mb deletion of chromosome Ip. The identification of two deletions in 27 cases gave an aberration frequency of 7.5% without adjustment for marker informativeness (95% confidence interval 1-24%) and an estimated frequency of 18% if marker informativeness for monosomy was taken into account. This frequency is higher than previous estimates of the number of subtelomeric chromosome abnormalities in children with idiopathic mental retardation (5-10%) although the confidence interval is overlapping. Our study suggests that in spite of the low informativeness of this pilot screening, submicroscopic chromosome aberrations may be a common cause of dysmorphic features and mental retardation. C1 Univ Manchester, St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England. Univ Manchester, St Marys Hosp, Reg Genet Serv, Manchester M13 0JH, Lancs, England. Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. John Radcliffe Hosp, Inst Mol Med, Oxford OX3 9DU, England. Trafford Gen Hosp, Dept Paediat, Trafford NHS Trust, Manchester M41 5SL, Lancs, England. RP Campbell, RHA (reprint author), Univ Manchester, St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England. NR 53 TC 115 Z9 118 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD MAY PY 1999 VL 36 IS 5 BP 405 EP 411 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 196CD UT WOS:000080290700011 PM 10353788 ER PT J AU Haspel, HC Stephenson, KN Davies-Hill, T El-Barbary, A Lobo, JF Croxen, RL Mougrabi, W Koehler-Stec, EM Fenstermacher, JD Simpson, IA AF Haspel, HC Stephenson, KN Davies-Hill, T El-Barbary, A Lobo, JF Croxen, RL Mougrabi, W Koehler-Stec, EM Fenstermacher, JD Simpson, IA TI Effects of barbiturates on facilitative glucose transporters are pharmacologically specific and isoform selective SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE barbiturates; glucose transport; anesthetics; pharmacologic specificity; isoform selectivity; binding ID HUMAN ERYTHROCYTES; HEXOSE-TRANSPORT; BRAIN; RAT; PROTEINS; EXPRESSION; INHIBITION; ANESTHESIA; REGIONS; NEURONS AB Barbiturates inhibit GLUT-1-mediated glucose transport across the blood-brain barrier, in cultured mammalian cells, and in human erythrocytes. Barbiturates also interact directly with GLUT-1. The hypotheses that this inhibition of glucose transport is (i) selective, preferring barbiturates over halogenated hydrocarbon inhalation anesthetics, and (ii) specific, favoring some GLUT-# isoforms over others were tested. Several oxy- and thio-barbiturates inhibited [H-3]-2-deoxyglucose uptake by GLUT-1 expressing murine fibroblasts with IC(50)s of 0.2-2.9 mM. Inhibition of GLUT-1 by barbiturates correlates with their overall lipid solubility and pharmacology, and requires hydrophobic side chains on the core barbiturate structure. In contrast, several halogenated hydrocarbons and ethanol (all less than or equal to 10 mM) do not significantly inhibit glucose transport. The interaction of these three classes of anesthetics with purified GLUT-1 was evaluated by quenching of intrinsic protein fluorescence and displayed similar specificities and characteristics. The ability of barbiturates to inhibit other facilitative glucose transporters was determined in cell types expressing predominantly one isoform. Pentobarbital inhibits [H-3]-2-deoxyglucose and [C-14]-3-O-methyl-glucose uptake in cells expressing GLUT-1, GLUT-2, and GLUT-3 with IC(50)s of similar to 1 mM. In contrast, GLUT-4 expressed in insulin-stimulated rat adipocytes was much less sensitive than the other isoforms to inhibition by pentobarbital (IC50 of >10 mM). Thus, barbiturates selectively inhibit glucose transport by some, but not all, facilitative glucose transporter isoforms. C1 Henry Ford Hlth Syst, Dept Anesthesiol, Detroit, MI 48202 USA. NIDDK, Expt Diabet Metab & Nutr Sect, NIH, Bethesda, MD 20892 USA. RP Haspel, HC (reprint author), Henry Ford Hlth Syst, Dept Anesthesiol, 1FP-4D,1 Ford Pl, Detroit, MI 48202 USA. FU NINDS NIH HHS [NS-26004] NR 32 TC 27 Z9 29 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-2631 EI 1432-1424 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD MAY 1 PY 1999 VL 169 IS 1 BP 45 EP 53 DI 10.1007/PL00005900 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 190GT UT WOS:000079955000005 PM 10227851 ER PT J AU Cude, KJ Dixon, SC Guo, Y Lisella, J Figg, WD AF Cude, KJ Dixon, SC Guo, Y Lisella, J Figg, WD TI The androgen receptor: genetic considerations in the development and treatment of prostate cancer SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE androgen receptor; prostate cancer; hormone ablation ID EPIDERMAL GROWTH-FACTOR; DNA-BINDING DOMAIN; GLUCOCORTICOID RECEPTOR; TRANSCRIPTIONAL ACTIVATION; ACID-PHOSPHATASE; BREAST-CANCER; CELL-LINES; MOLECULAR MECHANISMS; LIGAND-BINDING; HSP90 BINDING AB The action of androgens in the development and growth of prostate carcinomas is well documented. The androgen receptor (AR) facilitates androgen-induced regulation of genes involved in cellular proliferation and differentiation. Since he early 1940s androgen ablation has been the cornerstone of treatment for metastatic prostate cancer. Although initially highly effective, hormonal therapy is not curative, and resistant disease will ultimately prevail. Mutations that alter AR conformation, function, and regulation may provide a selective growth advantage for subpopulations of cells within the tumor that are then able to proliferate in an androgen-deprived environment. Clinically, these mutations are important because they may lead to the growth of androgen-independent tumors and progression to a refractory state. Further characterization of AR mutations will lead to a more thorough understanding of their role in the development of prostate carcinomas. This information, in addition to discovering which genes are regulated by the AR, can aid in the future development of more effective pharmacotherapy for prostate cancer. C1 NCI, Med Branch, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Med Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 80 TC 32 Z9 34 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 MAY PY 1999 VL 77 IS 5 BP 419 EP 426 DI 10.1007/s001090050372 PG 8 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 207TW UT WOS:000080952700005 PM 10426191 ER PT J AU Sellers, JR AF Sellers, JR TI Unphosphorylated crossbridges and latch: smooth muscle regulation revisited SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Editorial Material ID ACTIN-ACTIVATED ATPASE; VITRO MOTILITY ASSAY; HEAVY-MEROMYOSIN; IN-VITRO; MYOSIN; PHOSPHORYLATION; COOPERATIVITY; BINDING C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Sellers, JR (reprint author), NHLBI, NIH, Bldg 10,Room 8N202, Bethesda, MD 20892 USA. NR 21 TC 8 Z9 8 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PD MAY PY 1999 VL 20 IS 4 BP 347 EP 349 DI 10.1023/A:1005557724418 PG 3 WC Cell Biology SC Cell Biology GA 234XJ UT WOS:000082509400001 PM 10531615 ER PT J AU Vidwans, AS Kim, S Coffin, DO Wink, DA Hewett, SJ AF Vidwans, AS Kim, S Coffin, DO Wink, DA Hewett, SJ TI Analysis of the neuroprotective effects of various nitric oxide donor compounds in murine mixed cortical cell culture SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE nitric oxide donors; NMDA-induced neurotoxicity; murine mixed cortical cell culture; NONOate-type nitric oxide donors; S-nitrosothiols ID METHYL-D-ASPARTATE; NMDA-RECEPTOR ACTIVATION; LOW-DENSITY-LIPOPROTEIN; LIPID-PEROXIDATION; REACTIVE OXYGEN; GLUTAMATE-RECEPTOR; FOREBRAIN NEURONS; INDUCED BLOCKADE; N-NITROSATION; L-ARGININE AB Nitric oxide (NO) has been implicated in both the pathogenesis of and protection from NMDA receptor-mediated neuronal injury. This apparent paradox has been attributed to alternate redox states of nitrogen monoxide, whereby, depending on the redox milieu, nitrogen monoxide can be neuroprotective via nitrosation chemistry or react with superoxide to form secondary toxic species. in our murine mixed cortical cell culture system, the NONOate-type NO donors diethylamine/NO complex sodium (Dea/NO), (Z)-[N-(3-ammoniopropyl)-N-(n-propyl)amino]diazen-1 -ium-1,2-diolate (Papa/NO), and spermine/NO complex sodium (Sper/NO), as well as the S-nitrosothiols S-nitroso-L-glutathione (GSNO) and S-nitroso-N-acetyl-D,L-penicillamine (SNAP) (NO+ equivalents), decreased NMDA-induced neuronal injury in a concentration-dependent manner. 8-Bromo-cyclic GMP did not mimic the inhibitory effects of the donors, suggesting that the neuroprotection was not the result of NO-stimulated neuronal cyclic GMP production. Furthermore, neuronal injury induced by exposure of cultures to H2O2 was not altered by the presence of Dea/NO, indicating the absence of a direct antioxidant effect. NONO-ates did, however, reduce NMDA-stimulated uptake of Ca-45(2+), whereas high potassium-induced Ca-45(2+) accumulation, a measurement of entry via voltage-gated calcium channels, was unaffected. The parallel reduction of 45Ca2+ accumulation and NMDA neurotoxicity by NONOates mimicked that seen with an NMDA receptor antagonist. Electrochemical measurements of NO via an NO-sensitive electrode demonstrated that neuroprotective concentrations of all donors produced appreciable amounts of NO over the 5-min time frame, Determination of the formation of NO+ equivalents, as assessed by N-nitrosation of 2,3-diaminonaphthylene, revealed little or no observable N-nitrosation by Sper/NO, GSNO, and SNAP with significant N-nitrosation observed by Papa/NO and Dea/NO. However, addition of ascorbate (400 mu M) effectively prevented the nitrosation of 2,3-diaminonaphthylene produced by Dea/NO and Papa/NO without altering their neuroprotective properties or their effects on Ca-45(2+) accumulation. Present results indicate that the intrinsic NO/NO+ characteristics of NO donor compounds may not be a good predictor of their ability to inhibit NMDA receptor-mediated neurotoxicity at the cellular level. C1 Univ Connecticut, Ctr Hlth, Dept Pharmacol, Program Neurosci, Farmington, CT 06030 USA. Univ Connecticut, Ctr Hlth, Dept Pediat, Div Neonatol, Farmington, CT 06030 USA. NCI, Tumor Biol Sect, Radiat Biol Branch, Bethesda, MD 20892 USA. RP Hewett, SJ (reprint author), Univ Connecticut, Ctr Hlth, Dept Pharmacol, Program Neurosci, MC-6125,263 Farmington Ave, Farmington, CT 06030 USA. OI Hewett, Sandra/0000-0002-2987-3791 FU NINDS NIH HHS [R01 NS036812] NR 68 TC 57 Z9 57 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 1999 VL 72 IS 5 BP 1843 EP 1852 DI 10.1046/j.1471-4159.1999.0721843.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 186WJ UT WOS:000079753400007 PM 10217260 ER PT J AU Yang, HYT Karoum, F Felder, C Badger, H Wang, TCL Markey, SP AF Yang, HYT Karoum, F Felder, C Badger, H Wang, TCL Markey, SP TI GC/MS analysis of anandamide and quantification of N-arachidonoylphosphatidylethanolamides in various brain regions, spinal cord, testis, and spleen of the rat SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE anandamide; N-arachidonoylphosphatidylethanolamides; endogenous cannabinoid; gas chromatography mass spectrometry; deuterium labeling; reverse-phase C-18 cartridge ID ENDOGENOUS CANNABINOID PRECURSOR; ENZYMATIC-SYNTHESIS; PERIPHERAL-TISSUES; RECEPTOR AGONIST; CENTRAL NEURONS; PHOSPHOLIPASE-D; LIGAND; ACYLETHANOLAMINES; PHOSPHODIESTERASE; BIOSYNTHESIS AB Anandamide [N-arachidonoylethanolamide (NAE)] was initially isolated from porcine brain and proposed as an endogenous ligand for cannabinoid receptors in 1992. Accumulating evidence has now suggested that, in the tissue, NAE is generated from N-arachidonoylphosphatidylethanolamides (N-ArPEs) by phosphodiesterase, In this study a sensitive and specific procedure was developed to quantify NAE and N-ArPE, including organic solvent extraction, reverse-phase C-18 cartridge separation, derivatization, and gas chromatography/mass spectrometry (GC/MS) analysis, NAE is converted by a two-step derivatization procedure to a pentafluorobenzoyl ester followed by pentafluoropropionyl acylation, Quantification was performed by isotope dilution GC/MS using deuterium-labeled NAE (NAE-H-2(8)) as an internal standard. The same chemical derivatization was applicable to N-ArPE quantification. The separated N-ArPE fractions were converted by a two-step cleavage/derivatization procedure into the pentafluorobenzoyl ester of NAE and then to its pentafluoropropionyl amide, The derivative was quantified by GC/MS using deuterium-labeled 1,2[H-2(8)]dioleoyl-sn-glycero-3-phospho(arachidonoyl)ethanolamide as an internal standard. Using these methods, we have found that endogenous NAE levels in rat brain, spleen, testis, liver, lung, and heart were below the level of quantification achievable (0.1 pmol/mg of protein) but that N-ArPE is readily quantifiable and is widely distributed in the rat CNS with the highest level in the spinal cord. The striatum, hippocampus, and accumbens contain intermediate concentrations of N-ArPE, whereas the value is lowest in the cerebellum. C1 NIMH, Lab Neurotoxicol, Bethesda, MD 20892 USA. St Elizabeth Hosp, Ctr Neurosci, NIMH, Washington, DC 20032 USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Markey, SP (reprint author), NIMH, Lab Neurotoxicol, Bldg 10,Room 3D42, Bethesda, MD 20892 USA. NR 38 TC 51 Z9 53 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 1999 VL 72 IS 5 BP 1959 EP 1968 DI 10.1046/j.1471-4159.1999.0721959.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 186WJ UT WOS:000079753400020 PM 10217273 ER PT J AU Morrison, PF Morishige, GM Beagles, KE Heyes, MP AF Morrison, PF Morishige, GM Beagles, KE Heyes, MP TI Quinolinic acid is extruded from the brain by a probenecid-sensitive carrier system: A quantitative analysis SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE quinolinic acid; probenecid; in vivo microdialysis; blood-brain barrier; efflux transport ID CONVERT L-TRYPTOPHAN; CEREBROSPINAL-FLUID; NEUROACTIVE KYNURENINES; HEPATIC-ENCEPHALOPATHY; IMMUNE ACTIVATION; AMINE METABOLITES; RAT-BRAIN; MICRODIALYSIS; BLOOD; MECHANISM AB Although the neurotoxic tryptophan-kynurenine pathway metabolite quinolinic acid originates in brain by both local de novo synthesis and entry from blood, its concentrations in brain parenchyma, extracellular fluid, and CSF are normally below blood values. In the present study, an intraperitoneal injection of probenecid (400 mg/kg), an established inhibitor of acid metabolite transport in brain, into gerbils, increased quinolinic acid concentrations in striatal homogenates, CSF, serum, and homogenates of kidney and liver. Direct administration of probenecid (10 mM) into the brain compartment via an in vivo microdialysis probe implanted into the striatum also caused a progressive elevation in both quinolinic acid and homovanillic acid concentrations in the extracellular fluid compartment but was without effect on serum quinolinic acid levels. A model of microdialysis transport showed that the elevations in extracellular fluid quinolinic acid and homovanillic acid levels following intrastriatal application are consistent with probenecid block of a microvascular acid transport mechanism. We conclude that quinolinic acid in brain is maintained at concentrations below blood levels largely by active extrusion via a probenecid-sensitive carrier system. C1 NIMH, Lab Neurotoxicol, NIH, Bethesda, MD 20892 USA. NIMH, Off Res Serv, Bioengn & Phys Sci Program, NIH, Bethesda, MD 20892 USA. RP Heyes, MP (reprint author), NIMH, Lab Neurotoxicol, NIH, Bldg 10,Room 3D40,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 45 TC 22 Z9 23 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 1999 VL 72 IS 5 BP 2135 EP 2144 DI 10.1046/j.1471-4159.1999.0722135.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 186WJ UT WOS:000079753400042 PM 10217295 ER PT J AU Arima, H Kondo, K Kakiya, S Nagasaki, H Yokoi, H Yambe, Y Murase, T Iwasaki, Y Oiso, Y AF Arima, H Kondo, K Kakiya, S Nagasaki, H Yokoi, H Yambe, Y Murase, T Iwasaki, Y Oiso, Y TI Rapid and sensitive vasopressin heteronuclear RNA responses to changes in plasma osmolality SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE vasopressin; heteronuclear RNA; paraventricular nucleus; supraoptic nucleus; in-situ hybridization ID CORTICOTROPIN-RELEASING-HORMONE; INSITU HYBRIDIZATION ANALYSIS; MESSENGER-RNA; ARGININE-VASOPRESSIN; PARAVENTRICULAR NUCLEUS; GENE-TRANSCRIPTION; HYPOTHALAMIC NUCLEI; ACUTE STRESS; RATS; SECRETION AB The plasma concentration of arginine vasopressin (AVP) is closely regulated by plasma osmolality. In this study, we used intronic in-situ hybridization to investigate the transcriptional activity of the AVP gene in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) after intraperitoneal (i.p.) injection of hypertonic saline inducing small changes in plasma osmolality in rats. After ip injection of 900 mOsm/kg saline (2% BW), plasma [Na] reached the highest level at 10 min (900 mOsm/kg, 146 +/- 1 mEq/l; 290 mOsm/kg, 139 +/- 1 mEq/l, P < 0.01) and maintained that level until 30 min. The expression of AVP heteronuclear (hn) RNA in the SON and PVN increased significantly as early as 10 min and peaked 30 min after ip injection of the hypertonic saline. AVP hnRNA expression showed a significant increase even after a 2 mEq/L elevation in plasma [Na] concentration, and increased dose-dependently in response to the concentration of saline injection (290-900 mOsm/kg). These results demonstrate that, similar to AVP secretion, AVP gene transcriptional activity in the SON and PVN is closely regulated by plasma osmolality. C1 Nagoya Univ, Sch Med, Dept Internal Med 1, Nagoya, Aichi 466, Japan. RP Arima, H (reprint author), NICHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. RI chen, xuanlan/H-4158-2011; Arima, Hiroshi/I-7383-2014 OI Arima, Hiroshi/0000-0003-3746-1997 NR 27 TC 58 Z9 58 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD MAY PY 1999 VL 11 IS 5 BP 337 EP 341 PG 5 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 194FD UT WOS:000080180700004 PM 10320560 ER PT J AU Sugita, Y Zhao, BY Shankar, P Dunbar, CE Doren, S Young, HA Schwartz, JP AF Sugita, Y Zhao, BY Shankar, P Dunbar, CE Doren, S Young, HA Schwartz, JP TI CNS interleukin-3 (IL-3) expression and neurological syndrome in antisense-IL-3 transgenic mice SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE antisense mRNA; astrocytes; interleukin-3; microglia; neuronal death; reactive gliosis; transgenic mice ID CENTRAL-NERVOUS-SYSTEM; MONOCYTE CHEMOATTRACTANT PROTEIN-1; COLONY-STIMULATING FACTORS; DIFFERENTIATION IN-VITRO; GROWTH-FACTOR; MICROGLIAL ACTIVATION; RAT; ASTROCYTES; CYTOKINE; BRAIN AB Interleukin-3 (IL-3) is an important mediator of physiological and pathophysiological processes affecting the central nervous system (CNS). It stimulates the proliferation and activation of microglia and can enhance differentiation of cholinergic and sensory neurons. To examine the role of IL-3 in the CNS, we utilized transgenic mice expressing a murine antisense IL-3 (AS-IL-3) RNA under the control of the T cell B19 promoter so that expression is limited to hematopoietic cells. The AS-IL-3 transgenic mice develop either a progressive neurologic dysfunction, which includes ataxia, bradykinesia, and paralysis, or a lymphoproliferative syndrome. Histopathology demonstrated accumulations of reactive astrocytes in the cerebellum, brain stem, and spinal cord, accompanied by activated microglia. partial loss of cerebellar nuclei neurons as well as neurons in the cranial nerve nuclei and spinal cord motor neurons is seen. Despite depletion of IL-3 peripherally, expression of IL-3 mRNA and protein is turned on in the CNS of the transgenic mice. Astrocytes cultured from the AS-IL-3 mice contain IL-3 mRNA and may thus be responsible for the activation of the microglia. This model should provide important insights into the role of cytokines in neurological disorders. C1 NINDS, Neurotroph Factors Sect, NIH, Mol Genet Sect,Clin Neurosci Branch, Bethesda, MD 20892 USA. NHLBI, Expt Immunol Lab, Bethesda, MD 20892 USA. NCI, FCRDC, NIH, Bethesda, MD USA. NINDS, Hematol Branch, Bethesda, MD 20892 USA. RP Schwartz, JP (reprint author), NINDS, Neurotroph Factors Sect, NIH, Mol Genet Sect,Clin Neurosci Branch, Bldg 36,Rm 4A27, Bethesda, MD 20892 USA. NR 31 TC 13 Z9 14 U1 0 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1999 VL 58 IS 5 BP 480 EP 488 DI 10.1097/00005072-199905000-00007 PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 194PA UT WOS:000080201700007 PM 10331436 ER PT J AU Lieberman, AP Trojanowski, JQ Leonard, DGB Barnett, JL Leverenz, J Robitaille, Y Malandrini, A Fischbeck, KH AF Lieberman, AP Trojanowski, JQ Leonard, DGB Barnett, JL Leverenz, J Robitaille, Y Malandrini, A Fischbeck, KH TI Ataxin 1 and ataxin 3 in neuronal intranuclear inclusion disease. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 NINDS, Neurogenet Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1999 VL 58 IS 5 MA 26 BP 515 EP 515 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 194PA UT WOS:000080201700037 ER PT J AU Colvin, SM Weickert, CS Clingenpeel, RA Webster, MJ Poulin, P Hyde, TM Kleinman, JE AF Colvin, SM Weickert, CS Clingenpeel, RA Webster, MJ Poulin, P Hyde, TM Kleinman, JE TI Evidence of neurogenesis in the subependymal zone of postnatal human brain SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, IRP, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1999 VL 58 IS 5 MA 39 BP 519 EP 519 DI 10.1097/00005072-199905000-00050 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 194PA UT WOS:000080201700050 ER PT J AU Oya, Y Proia, R Norflus, F Tifft, C Langaman, C Suzuki, K AF Oya, Y Proia, R Norflus, F Tifft, C Langaman, C Suzuki, K TI Histochemical localization of beta hexosaminidase in GM(2)gangliosidoses mice SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Univ N Carolina, Chapel Hill, NC USA. Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1999 VL 58 IS 5 MA 55 BP 523 EP 523 DI 10.1097/00005072-199905000-00066 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 194PA UT WOS:000080201700066 ER PT J AU Fuller, BG Moon, YW Zhuang, Z Vortmeyer, AO Mena, H Wong, K AF Fuller, BG Moon, YW Zhuang, Z Vortmeyer, AO Mena, H Wong, K TI Polymerase chain reaction (PCR), single-strand conformational polymorphism (SSCP) mutation analysis of uracil DNA glycosylase gene (UNG) in 32 cases of glioblastoma multiforme (GBM) SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Armed Forces Inst Pathol, Washington, DC 20306 USA. NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1999 VL 58 IS 5 MA 108 BP 536 EP 536 DI 10.1097/00005072-199905000-00119 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 194PA UT WOS:000080201700119 ER PT J AU Lippa, CF Zhukareva, V St George-Hyslop, P Nee, L Grafman, J Tresser, N Trojanowski, JQ Lee, VMY AF Lippa, CF Zhukareva, V St George-Hyslop, P Nee, L Grafman, J Tresser, N Trojanowski, JQ Lee, VMY TI A novel pattern of tau isoforms in familial Pick's disease. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Med Coll Penn & Hahnemann Univ, Philadelphia, PA USA. Univ Penn, Philadelphia, PA 19104 USA. NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1999 VL 58 IS 5 MA 149 BP 546 EP 546 DI 10.1097/00005072-199905000-00160 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 194PA UT WOS:000080201700160 ER PT J AU Gold, M Rojiani, AM Parchi, P Gambetti, P Gibbs, CJ Kenney, K AF Gold, M Rojiani, AM Parchi, P Gambetti, P Gibbs, CJ Kenney, K TI Sporadic Creutzfeldt-Jakob disease (sCJD) - A southwest Florida experience. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Univ S Florida, Tampa, FL USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Natl Inst Hlth, Bethesda, MD USA. RI Parchi, Piero/L-9833-2015 OI Parchi, Piero/0000-0002-9444-9524 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1999 VL 58 IS 5 MA 171 BP 552 EP 552 DI 10.1097/00005072-199905000-00182 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 194PA UT WOS:000080201700182 ER PT J AU Brustle, O Jones, KN Learish, R Karram, K Choudhary, K Wiestler, OD Duncan, ID McKay, RDG AF Brustle, O Jones, KN Learish, R Karram, K Choudhary, K Wiestler, OD Duncan, ID McKay, RDG TI Transplanted embryonic stem cell-derived glial precursors repair CNS myelin. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Univ Bonn, Med Ctr, D-5300 Bonn, Germany. NINDS, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Madison, WI 53706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1999 VL 58 IS 5 MA 190 BP 556 EP 556 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 194PA UT WOS:000080201700201 ER PT J AU Whetsell, WO Reddy, PH Charles, V Tagle, DA AF Whetsell, WO Reddy, PH Charles, V Tagle, DA TI Evaluation of neuropathologic changes in striatum and cerebral cortex of transgenic mice expressing full-length human HD cDNA: A new model for Huntington's disease. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Vanderbilt Univ, Nashville, TN USA. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. NR 2 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1999 VL 58 IS 5 MA 205 BP 560 EP 560 DI 10.1097/00005072-199905000-00216 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 194PA UT WOS:000080201700216 ER PT J AU Ruskin, DN Bergstrom, DA Kaneoke, Y Patel, BN Twery, MJ Walters, JR AF Ruskin, DN Bergstrom, DA Kaneoke, Y Patel, BN Twery, MJ Walters, JR TI Multisecond oscillations in firing rate in the basal ganglia: Robust modulation by dopamine receptor activation and anesthesia SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID NIGRA PARS RETICULATA; MOUSE HIPPOCAMPAL-NEURONS; GLOBUS-PALLIDUS; SUBSTANTIA-NIGRA; FUNCTIONAL CONNECTIVITY; SUBTHALAMIC NUCLEUS; LIMBIC SYSTEM; TIME-SERIES; MPTP MODEL; MONKEY AB Studies of CNS electrophysiology have suggested an important role for oscillatory neuronal activity in sensory perception, sensorimotor integration, and movement timing. In extracellular single-unit recording studies in awake, immobilized rats, we have found that many tonically active neurons in the entopeduncular nucleus tit = 15, globus pallidus (n = 31), and substantia nigra pars reticulata (n = 31) have slow oscillations in firing rate in the seconds-to-minutes range. Basal oscillation amplitude ranged up to +/-50% of the mean firing rate. Spectral analysis was performed on spike trains to determine whether these multisecond oscillations were significantly periodic. Significant activity in power spectra tin the 2- to 60-s range of periods from basal spike trains was found for 56% of neurons in these three nuclei. Spectral peaks corresponded to oscillations with mean periods of similar to 30 s in each nucleus. Multisecond baseline oscillations were also found in 21% of substantia nigra dopaminergic neurons. The dopamine agonist apomorphine (0.32 mg/kg iv, n = 10-15) profoundly affected multisecond oscillations, increasing oscillatory frequency (means of spectral peak periods were reduced to similar to 15 s) and increasing the regularity of the oscillations. Apomorphine effects on oscillations in firing rate were more consistent from unit to unit than were its effects on mean firing rates in the entopeduncular nucleus and substantia nigra. Apomorphine modulation of multisecond periodic oscillations was reversed by either D-1, or D-2, antagonists and was mimicked by the combination of selective D-1, (SKF-81297) and D-2, (quinpirole) agonists. Seventeen percent of neurons had additional baseline periodic activity in a faster range (0.4-2.0 s) related to ventilation. Multisecond periodicities were rarely found in neurons in anesthetized rats (n = 29), suggesting that this phenomenon is sensitive to overall reductions in central activity. The data demonstrate significant structure in basal ganglia neuron spiking activity at unexpectedly long time scales, as well as a novel effect of dopamine on firing pattern in this slow temporal domain. The modulation of multisecond periodicities in firing rate by dopaminergic agonists suggests the involvement of these patterns in behaviors and cognitive processes that are affected by dopamine. Periodic firing rate oscillations in basal ganglia output nuclei should strongly affect the firing patterns of target neurons and are likely involved in coordinating neural activity responsible for motor sequences. Modulation of slow, periodic oscillations in firing rate may be an important mechanism by which dopamine influences motor and cognitive processes in normal and dysfunctional states. C1 NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Physiol Sci, Dept Integrat Physiol, Okazaki, Aichi 4448585, Japan. RP Ruskin, DN (reprint author), Bldg 10,Rm 5C-103,10 Ctr Dr, Bethesda, MD 20892 USA. NR 50 TC 96 Z9 99 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 1999 VL 81 IS 5 BP 2046 EP 2055 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 198YU UT WOS:000080452900006 PM 10322046 ER PT J AU Caddick, SJ Wang, CS Fletcher, CF Jenkins, NA Copeland, NG Hosford, DA AF Caddick, SJ Wang, CS Fletcher, CF Jenkins, NA Copeland, NG Hosford, DA TI Excitatory but not inhibitory synaptic transmission is reduced in lethargic(Cacnb4(1h)) and tottering (Cacnala(tg)) mouse thalami SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID GENERALIZED ABSENCE SEIZURES; CHANNEL BETA-SUBUNIT; PRESYNAPTIC CALCIUM CHANNELS; GABA(B) RECEPTORS; CA2+ CHANNELS; GAMMA-HYDROXYBUTYRATE; CELLULAR MECHANISMS; RELAY NEURONS; T-TYPE; CURRENTS AB Recent studies of the homozygous tottering (Cacnala(tg)) and lethargic mouse (Cacnb4(lh)) models of absence seizures have identified mutations in the genes encoding the alpha 1A and beta 4 subunits, respectively, of voltage-gated Ca2+ channels (VGCCs). beta subunits normally regulate Ca2+ currents via a direct interaction with alpha 1 (pore-forming) subunits of VGCCs, and VGCCs are known to play a significant role in controlling the release of transmitter from presynaptic nerve terminals in the CNS. Because the gene mutation in Cacnb4lh homozygotes results in loss of the beta 4 subunit's binding site for alpha 1 subunits, we hypothesized that synaptic transmission would be altered in the CNS of Cacnb4(lh) homozygotes. We tested this hypothesis: by using whole cell recordings of single cells in an in vitro slice preparation to investigate synaptic transmission in one of the critical neuronal populations that generate seizure activity in this strain, the somatosensory thalamus. The primary finding reported here is the observation of a significant decrease in glutamatergic synaptic transmission mediated by both N-methyl-D-aspartate (NMDA) and non-NMDA receptors in somatosensory thalamic neurons of Cacnb4(lh) homozygotes compared with matched, nonepileptic mice. In contrast, there was no significant decrease in GABAergic transmission in Cacnb4lh homozygotes nor was there any difference in effects mediated by presynaptic GABA, receptors. We found a similar decrease in glutamatergic but not GABAergic responses in Cacnb4(lh) homozygotes, suggesting that the independent mutations in the two strains each affected P/Q channel function by causing defective neurotransmitter release specific to glutamatergic synapses in the somatosensory thalamus. This may bean important factor underlying the generation of seizures in these models. C1 Duke Univ, Dept Med Neurol, Durham, NC 27705 USA. Vet Adm Med Ctr, Durham, NC 27705 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Neurol, Richmond, VA 23298 USA. Duke Univ, Med Ctr, Dept Med, Div Neurol, Durham, NC 27705 USA. Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27705 USA. NCI, Mammalian Genet Lab, Adv Biosci Labs,Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Hosford, DA (reprint author), Duke Univ, Dept Med Neurol, Bldg 16,Rm 38,508 Fulton St, Durham, NC 27705 USA. FU NINDS NIH HHS [NS-30977] NR 58 TC 87 Z9 88 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 1999 VL 81 IS 5 BP 2066 EP 2074 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 198YU UT WOS:000080452900008 PM 10322048 ER PT J AU Xiong, KM Peoples, RW Montgomery, JP Chiang, YS Stewart, RR Weight, FF Li, CY AF Xiong, KM Peoples, RW Montgomery, JP Chiang, YS Stewart, RR Weight, FF Li, CY TI Differential modulation by copper and zinc of P2X(2) and P2X(4) receptor function SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID NODOSE GANGLION NEURONS; FAST SYNAPTIC TRANSMISSION; ATP-ACTIVATED CHANNELS; CENTRAL-NERVOUS-SYSTEM; GATED ION CHANNELS; MAMMALIAN NEURONS; SENSORY NEURONS; RAT-BRAIN; SPINAL-CORD; CURRENTS AB The modulation by CU2+ and Zn2+ of P2X(2) and P2X(4) receptors expressed in Xenopus oocytes was studied with the two-electrode, voltage-clamp technique. In oocytes expressing P2X(2) receptors, both CU2+ and Zn2+ in the concentration range 1-130 mu M, reversibly potentiated current activated by submaximal concentrations of ATP. The CU2+,and Zn2+ concentrations that produced 50% of maximal potentiation (EC50) of current activated by 50 mu M ATP were 16.3 If: 0.9 (SE) ELM and 19.6 +/- 1.5 mu M, respectively. CU2+,and Zn2+ potentiation of ATP-activated current was independent of membrane potential between -80 and +20 mV and did not involve a shift in the reversal potential of the current. Like Zn2+, CU2+ increased the apparent affinity of the receptor for ATP, as evidenced by a parallel shift of the ATP concentration-response curve to the left. However, CU2+ did not enhance ATP-activated current in the presence of a;maximally effective concentration of Zn2+, suggesting a common site or mechanism of action of CU2+ and Zn2+ on P2X(2) receptors. For the P2X(4) receptor, Zn2+, from 0.5 to 20 mu M enhanced current activated by 5 mu M ATP with an EC50 value of 2.4 +/- 0.2 mu M. Zn2+ Shifted the ATP concentration-response curve to the left in a parallel manner, and potentiation by Zn2+ was voltage independent. By contrast, CU2+ in a similar concentration range did not affect ATP-activated current in oocytes expressing P2X(4), receptors, and CU2+ did not alter the potentiation of ATP-activated current produced by Zn2+. The results su,suggest that CU2+ and Zn2+,zi differentially modulate the function of P2X(2), and P2X(4), receptors, perhaps because of differences in a shared site of action on both subunits or the absence of a site for Cu2+ action on the P2X(4), receptor. C1 NIAAA, Mol & Cellular Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Li, CY (reprint author), Astra Arcus USA Inc, Dept Cell Biol, Three Biotech, 1 Innovat Dr, Worcester, MA 01605 USA. NR 48 TC 78 Z9 79 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 MAY PY 1999 VL 81 IS 5 BP 2088 EP 2094 PG 7 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 198YU UT WOS:000080452900010 PM 10322050 ER PT J AU Ritter, A Wenner, P Ho, S Whelan, PJ O'Donovan, MJ AF Ritter, A Wenner, P Ho, S Whelan, PJ O'Donovan, MJ TI Activity patterns and synaptic organization of ventrally located interneurons in the embryonic chick spinal cord SO JOURNAL OF NEUROSCIENCE LA English DT Article DE spinal cord; rhythmic activity; interneurons; development; synchrony; chick ID SPONTANEOUS RHYTHMIC ACTIVITY; NEONATAL RAT; LUMBOSACRAL MOTONEURONS; NETWORKS; PROJECTIONS; NEURONS; GLYCINE; GABA; SYNAPSES; DRIVE AB To investigate the origin of spontaneous activity in developing spinal networks, we examined the activity patterns and synaptic organization of ventrally located lumbosacral interneurons, including those whose axons project into the ventrolateral funiculus (VLF), in embryonic day 9 (E9)-E12 chick embryos. During spontaneous episodes, rhythmic synaptic potentials were recorded from the VLF and from spinal interneurons that were synchronized, cycle by cycle, with rhythmic ventral root potentials. At the beginning of an episode, ventral root potentials started before the VLF discharge and the firing of individual interneurons. However, pharmacological blockade of recurrent motoneuron collaterals did not prevent or substantially delay interneuron recruitment during spontaneous episodes. The synaptic connections of interneurons were examined by stimulating the VLF and recording the potentials evoked in the ventral roots, in the VLF, or in individual interneurons. Low-intensity stimulation of the VLF evoked a short-latency depolarizing potential in the ventral roots, or in interneurons, that was probably mediated mono- or disynaptically. At higher intensities, long-latency responses were recruited in a highly nonlinear manner, eventually culminating in the activation of an episode. VLF-evoked potentials were reversibly blocked by extracellular Co2+, indicating that they were mediated by chemical synaptic transmission. Collectively, these findings indicate that ventral interneurons are rhythmically active, project to motoneurons, and are likely to be interconnected by recurrent excitatory synaptic connections. This pattern of organization may explain the synchronous activation of spinal neurons and the regenerative activation of spinal networks when provided with a suprathreshold stimulus. C1 NINDS, Sect Dev Neurobiol, Neural Control Lab, NIH, Bethesda, MD 20892 USA. RP O'Donovan, MJ (reprint author), NINDS, Sect Dev Neurobiol, Neural Control Lab, NIH, Room 3A50,Bldg 49, Bethesda, MD 20892 USA. RI o'donovan, michael/A-2357-2015; OI o'donovan, michael/0000-0003-2487-7547; Wenner, Peter/0000-0002-7072-2194 NR 39 TC 19 Z9 19 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 1 PY 1999 VL 19 IS 9 BP 3457 EP 3471 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 189BF UT WOS:000079883700020 PM 10212306 ER PT J AU Rios, M Habecker, B Sasaoka, T Eisenhofer, G Tian, H Landis, S Chikaraishi, D Roffler-Tarlov, S AF Rios, M Habecker, B Sasaoka, T Eisenhofer, G Tian, H Landis, S Chikaraishi, D Roffler-Tarlov, S TI Catecholamine synthesis is mediated by tyrosinase in the absence of tyrosine hydroxylase SO JOURNAL OF NEUROSCIENCE LA English DT Article DE catecholamines; tyrosine hydroxylase-null mutation; tyrosinase; tyrosine hydroxylase; tyrosinase and catecholamine synthesis; catecholamines in development; catecholamine synthesis ID MOUSE FETAL DEVELOPMENT; HUMAN SUBSTANTIA-NIGRA; TARGETED DISRUPTION; MICE; GENE AB Catecholamine neurotransmitters are synthesized by hydroxylation of tyrosine to L-dihydroxyphenylalanine (L-Dopa) by tyrosine hydroxylase (TH). The elimination of TH in both pigmented and albino mice described here, like pigmented TH-null mice reported previously (Kobayashi et al., 1995; Zhou et al., 1995), demonstrates the unequivocal requirement for catecholamines during embryonic development. Although the lack of TH is fatal, TH-null embryos can be rescued by administration of catecholamine precursors to pregnant darns. Once born, TH-null pups can survive without further treatment until weaning. Given the relatively rapid half-life of catecholamines, we expected to find none in postnatal TH-null pups. Despite the fact that the TH-null pups lack TH and have not been supplemented with catecholamine precursers, catecholamines are readily detected in our pigmented line of TH-null mice by glyoxylic acid-induced histofluorescence at postnatal day 7 (P7) and P15 and quantitatively at P15 in sympathetically innervated peripheral organs, in sympathetic ganglia, in adrenal glands, and in brains. Between 2 and 22% of wild-type catecholamine concentrations are found in these tissues in mutant pigmented mice. To ascertain the source of the catecholamine, we examined postnatal TH-null albino mice that lack tyrosinase, another enzyme that converts tyrosine to L-Dopa but does so during melanin synthesis. In contrast to the pigmented TH-null mice, catecholamine histofluorescence is undetectable in postnatal albino mutants, and the catecholamine content of TH-null pups lacking tyrosinase is 18% or less than that of TH-null mice with tyrosinase. Thus, these extraordinary circumstances reveal that tyrosinase serves as an alternative pathway to supply catecholamines. C1 Tufts Univ, Sch Med, Dept Neurosci, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Anat & Cell Biol, Boston, MA 02111 USA. NINDS, NIH, Bethesda, MD 20892 USA. Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Tokyo 187, Japan. Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA. RP Roffler-Tarlov, S (reprint author), 136 Harrison Ave, Boston, MA 02111 USA. RI Sasaoka, Toshikuni/N-9152-2015 OI Sasaoka, Toshikuni/0000-0002-7797-4394 FU NINDS NIH HHS [NS 31673] NR 21 TC 83 Z9 85 U1 1 U2 4 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 MAY 1 PY 1999 VL 19 IS 9 BP 3519 EP 3526 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 189BF UT WOS:000079883700025 PM 10212311 ER PT J AU Butts, DA Feller, MB Shatz, CJ Rokhsar, DS AF Butts, DA Feller, MB Shatz, CJ Rokhsar, DS TI Retinal waves are governed by collective network properties SO JOURNAL OF NEUROSCIENCE LA English DT Article DE visual system; development; calcium waves; model; developing retina; correlated activity ID DEVELOPING MAMMALIAN RETINA; STARBURST AMACRINE CELLS; GANGLION-CELLS; NEONATAL HIPPOCAMPUS; DEVELOPING NEOCORTEX; NEURONAL-ACTIVITY; SPINDLE WAVES; CHICK RETINA; OSCILLATIONS; MODEL AB Propagating neural activity in the developing mammalian retina is required for the normal patterning of retinothalamic connections. This activity exhibits a complex spatiotemporal pattern of initiation, propagation, and termination. Here, we discuss the behavior of a model of the developing retina using a combination of simulation and analytic calculation. Our model produces spatially and temporally restricted waves without requiring inhibition, consistent with the early depolarizing action of neurotransmitters in the retina. We find that highly correlated, temporally regular, and spatially restricted activity occurs over a range of network parameters; this ensures that such spatiotemporal patterns can be produced robustly by immature neural networks in which synaptic transmission by individual neurons may be unreliable. Wider variation of these parameters, however, results in several different regimes of wave behavior. We also present evidence that wave properties are locally determined by a single variable, the fraction of recruitable (i.e., nonrefractory) cells within the dendritic field of a retinal neuron. From this perspective, a given local area's ability to support waves with a wide range of propagation velocities-as observed in experiment-reflects the variability in the local state of excitability of that area. This prediction is supported by whole-cell voltage-clamp recordings, which measure significant wave-to-wave variability in the amount of synaptic input a cell receives when it participates in a wave. This approach to describing the developing retina provides unique insight into how the organization of a neural circuit can lead to the generation of complex correlated activity patterns. C1 Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA. Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Phys Biosci, Berkeley, CA 94720 USA. Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Butts, DA (reprint author), Univ Calif Berkeley, Dept Phys, 366 LeConte Hall, Berkeley, CA 94720 USA. RI Butts, Daniel/B-8346-2008 OI Butts, Daniel/0000-0002-0158-5317 FU NIMH NIH HHS [MH 48108] NR 42 TC 56 Z9 56 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 MAY 1 PY 1999 VL 19 IS 9 BP 3580 EP 3593 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 189BF UT WOS:000079883700031 PM 10212317 ER PT J AU Lieberman, DM Corthesy, HE Cummins, A Oldfield, EH AF Lieberman, DM Corthesy, HE Cummins, A Oldfield, EH TI Reversal of experimental parkinsonism by using selective chemical ablation of the medial globus pallidus SO JOURNAL OF NEUROSURGERY LA English DT Article DE pallidotomy; Parkinson's disease; excitotoxin; kainic acid; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Macaca mulatta ID GAMMA-KNIFE PALLIDOTOMY; KAINIC ACID; BASAL GANGLIA; POSTEROVENTRAL PALLIDOTOMY; SUBTHALAMIC NUCLEUS; MOVEMENT-DISORDERS; DRUG DISTRIBUTION; GPI PALLIDOTOMY; DISEASE; BRAIN AB Object. Symptoms from Parkinson's disease improve after surgical ablation of the medial globus pallidus (GPm). Although, in theory, selective chemical ablation of neurons in the GPm could preserve vital structures jeopardized by surgery, the potential of this approach is limited when using traditional techniques of drug delivery. The authors examined the feasibility of convection-enhanced distribution of a neurotoxin by high-flow microinfusion to ablate the neurons of the GPm selectively and reverse experimental Parkinson's disease (akinesia, tremor, and rigidity). Methods. Initially, to test the feasibility of this approach, the GPms of two naive rhesus macaques were infused with kainic acid or ibotenic acid through two cannulas that had been placed using the magnetic resonance imaging-guided stereotactic technique. Two weeks later the animals were killed and their brains were examined histologically to determine the presence of neurons in the GPm and the integrity of the optic tract and the internal capsule. To examine the therapeutic potential of this paradigm, unilateral experimental Parkinson's disease was induced in six macaques by intracarotid infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and their behavior was studied for 12 weeks after chemopallidotomy was performed using kainic acid (three animals) or control infusion (three animals). Conclusions. Chemopallidotomy using kainic acid permanently reversed the stigmata of MPTP-induced parkinsonism. By contrast, the control animals exhibited a transient recovery following intrapallidal infusion and then relapsed back to their baseline state. The use of high-flow microinfusion of selectively active toxins has the potential for treatment of Parkinson's disease and, by expanding the range of approachable targets to include large nuclei, for broad applications in clinical and experimental neuroscience. C1 NINDS, Surg Neurol Branch, Cent Nervous Syst Implantat Unit, NIH, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), NINDS, Surg Neurol Branch, Cent Nervous Syst Implantat Unit, NIH, I0-5D37,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 38 TC 16 Z9 16 U1 0 U2 2 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 MAY PY 1999 VL 90 IS 5 BP 928 EP 934 DI 10.3171/jns.1999.90.5.0928 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 189YT UT WOS:000079934600016 PM 10223460 ER PT J AU Brigger, P Bacharach, SL Srinivasan, G Nour, KA Carson, JA Dilsizian, V Aldroubi, A Unser, M AF Brigger, P Bacharach, SL Srinivasan, G Nour, KA Carson, JA Dilsizian, V Aldroubi, A Unser, M TI Segmentation of gated Tl-SPECT images and computation of ejection fraction: A different approach SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE Tl-201SPECT; gated blood pool imaging; FDG PET ID LEFT-VENTRICULAR FUNCTION; EMISSION COMPUTED-TOMOGRAPHY; MYOCARDIAL PERFUSION; PET/SPECT IMAGES; EDGE-DETECTION; QUANTIFICATION; QUANTITATION; PARAMETER AB Background. We describe a set of image processing algorithms and mathematical models that can be advantageously used in schemes for the segmentation of thallium-201-single photon emission computed tomography (SPECT) images and for computation of left ventricular ejection fraction (EF). Methods. The system consists of two independent blocs for image segmentation and computation of function. The former is based on a multiresolution elliptical coordinate transformation and dynamic contour tracking. Computation of EF is formulated on the basis of both the endocardial and epicardial contours, and we compare this formulation with that using only the endocardial border for images with low signal-to-noise ratios,The accuracy of border detection was validated against manual border tracing on FDG-PET images, simulated Tl-201-SPECT images where the true underlying borders were known, and actual Tl-201-SPECT images. Finally, we compared EFs computed for FDG-PET, technetium-99m-SPECT and Tl-201-SPECT with those obtained from planar gated blood pool imaging. Results. The automatically obtained results always were within the manual uncertainty range. Agreement between myocardial volumes from positron emission tomography and automatically obtained values from the simulated Tl-201-SPECT images was excellent (r = 0.95, n = 32), Agreement between EFs from planar gated blood pool imaging and the other image modalities was good (FDG-PET: y = 5.89 + 1.21x, r = 0.92, see = 6.24, n = 19, Tc-99m-SPECT: y = -3.86 + 1.06x, r = 0.88, see = 7.78, n = 9, Tl-201-SPECT: y = 17.8 + 0.81x, r = 0.77, see = 7.44, n = 26), For noisy input data the combined use of information from epicardial and endocardial contours gives more accurate EF values than the traditional formula on the basis of the endocardial contour only. Conclusions, Alternate approaches for segmentation and computation of function have been presented and validated. They might also be advantageously incorporated into other existing techniques. C1 NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Nashville, TN USA. Swiss Fed Inst Technol, CH-1015 Lausanne, Switzerland. RP Bacharach, SL (reprint author), NIH, Bldg 10,Rm 1C401, Bethesda, MD 20892 USA. EM Steve_Bacharach@nih.gov RI Unser, Michael/A-1550-2008; Aldroubi, Akram/J-7186-2012 NR 30 TC 4 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD MAY-JUN PY 1999 VL 6 IS 3 BP 286 EP 297 DI 10.1016/S1071-3581(99)90041-7 PG 12 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 207AA UT WOS:000080912100006 PM 10385184 ER PT J AU Carson, RE Kiesewetter, DO Connelly, K Mentis, MJ Cohen, RM Herscovitch, P Sunderland, T Eckelman, WC AF Carson, RE Kiesewetter, DO Connelly, K Mentis, MJ Cohen, RM Herscovitch, P Sunderland, T Eckelman, WC TI Kinetic analysis of the muscarinic cholinergic ligand [F-18]FP-TZTP in humans. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 6 Z9 6 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 MAY PY 1999 VL 40 IS 5 SU S MA 119 BP 30P EP 30P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800120 ER PT J AU Tenney, CR Smith, MF Tornai, MP Jaszczak, RJ AF Tenney, CR Smith, MF Tornai, MP Jaszczak, RJ TI Ultra-high resolution SPECT images with uranium pinhole collimators. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Durham, NC USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY PY 1999 VL 40 IS 5 SU S MA 138 BP 34P EP 34P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800139 ER PT J AU Lang, L Jagoda, E Sassaman, MB Magata, Y Eckelman, WC AF Lang, L Jagoda, E Sassaman, MB Magata, Y Eckelman, WC TI Comparison of F-18 labeled cis and trans 4-fluorocyclohexane derivatives of WAY 100635. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 8 Z9 8 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 MAY PY 1999 VL 40 IS 5 SU S MA 150 BP 37P EP 38P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800151 ER PT J AU Lang, L Jagoda, E Eckelman, WC AF Lang, L Jagoda, E Eckelman, WC TI New F-18 labeled way 100635 derivatives for the 5HT(1A) receptor. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 8 Z9 8 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 MAY PY 1999 VL 40 IS 5 SU S MA 149 BP 37P EP 37P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800150 ER PT J AU Herscovitch, P Lang, L Everett, JR Carson, RE Eckelman, WC AF Herscovitch, P Lang, L Everett, JR Carson, RE Eckelman, WC TI Biodistribution and radiation dose estimates for [F-18]FCWAY, an F-18 labeled 5-HT1A antagonist for PET. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 3 Z9 3 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 MAY PY 1999 VL 40 IS 5 SU S MA 168 BP 42P EP 42P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800169 ER PT J AU Norenberg, JP Garmestani, K Krenning, BJ Konings, IR Atcher, RW de Jong, M Srinivasan, A Kvols, LK Brechbeil, MW AF Norenberg, JP Garmestani, K Krenning, BJ Konings, IR Atcher, RW de Jong, M Srinivasan, A Kvols, LK Brechbeil, MW TI Radiolabellng methods for the preparation of [Bi-213-DITA(0),TYR3]octreotide (Bi-213-DOTATOC) for peptide receptor radionuclide therapy (PRRT). SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA. NCI, Chem Sect, Bethesda, MD 20892 USA. Univ Calif Los Alamos Natl Lab, Los Alamos, NM USA. Erasmus Univ, Rotterdam, Netherlands. Mallinckrodt Inc, St Louis, MO USA. NR 0 TC 1 Z9 1 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 MAY PY 1999 VL 40 IS 5 SU S MA 322 BP 80P EP 80P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800323 ER PT J AU Kim, MK Paik, DS Kao, CHK Le, N Jeong, HJ Kobayashi, H Brechbiel, MW Waldmann, TA Carrasquillo, JA Paik, CH AF Kim, MK Paik, DS Kao, CHK Le, N Jeong, HJ Kobayashi, H Brechbiel, MW Waldmann, TA Carrasquillo, JA Paik, CH TI Effect of isoelectric point on renal uptake of anti-Tac F(ab ')(2) labeled with Tc-99m-MAG3 and In-111-CHX-A ''. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 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 MAY PY 1999 VL 40 IS 5 SU S MA 327 BP 81P EP 81P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800328 ER PT J AU Garmestani, K Yordanov, AT Phillips, KE Beitzel, MP Schwarz, UP Rickford, MS Gansow, OA Plascjak, PS Eckelman, WC Brechbiel, MW Waldman, TA AF Garmestani, K Yordanov, AT Phillips, KE Beitzel, MP Schwarz, UP Rickford, MS Gansow, OA Plascjak, PS Eckelman, WC Brechbiel, MW Waldman, TA TI Preparation and in vivo stability evaluation of linkers for At-211 labeling of humanized anti-Tac(anti IL-2R alpha). SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY PY 1999 VL 40 IS 5 SU S MA 329 BP 82P EP 82P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800330 ER PT J AU Jousse, F Carrasquillo, JA Kage, R Whatley, M Libutti, SK Aloj, L Bacharach, SL AF Jousse, F Carrasquillo, JA Kage, R Whatley, M Libutti, SK Aloj, L Bacharach, SL TI Errors in quantification of lung FDG uptake due to blood volume of lung. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY PY 1999 VL 40 IS 5 SU S MA 385 BP 95P EP 95P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800386 ER PT J AU Norenberg, JP Krenning, BJ Konings, IR de Jong, M Srinivasan, A Garmestani, K Brechbiel, MW Kvols, LK AF Norenberg, JP Krenning, BJ Konings, IR de Jong, M Srinivasan, A Garmestani, K Brechbiel, MW Kvols, LK TI [213Bi-DOTA(0),TYR3]octreotide (Bi-213-DOTATOC) in peptide receptor radionuclide therapy (PRRT). SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Univ New Mexico, Albuquerque, NM 87131 USA. Erasmus Univ, Rotterdam, Netherlands. Mallinckrodt Inc, St Louis, MO USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 2 U2 2 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 MAY PY 1999 VL 40 IS 5 SU S MA 415 BP 103P EP 103P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800416 ER PT J AU Ma, D McDevitt, MR Barendswaard, E Curcio, MJ Lai, L Brechbiel, MW Finn, RD Scheinberg, DA AF Ma, D McDevitt, MR Barendswaard, E Curcio, MJ Lai, L Brechbiel, MW Finn, RD Scheinberg, DA TI Bi-213 labeled anti-CD19 antibody construct for lymphoma therapy. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 1 Z9 1 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 MAY PY 1999 VL 40 IS 5 SU S MA 431 BP 106P EP 107P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800432 ER PT J AU Wong, DF Rothman, RB Contoreggi, C Yokoi, F Stephane, M Dogan, S Schretlen, D Kuhar, M Gjedde, A AF Wong, DF Rothman, RB Contoreggi, C Yokoi, F Stephane, M Dogan, S Schretlen, D Kuhar, M Gjedde, A TI Dopamine transporter changes in cocaine users following one month abstinence. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD USA. NIDA, Addict Res Ctr, Baltimore, MD 21224 USA. Emory Univ, Atlanta, GA 30322 USA. Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. NR 0 TC 0 Z9 0 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 MAY PY 1999 VL 40 IS 5 SU S MA 441 BP 109P EP 109P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800442 ER PT J AU Heinz, A Jones, DW Mazzanti, C Goldman, D Hommer, D Linnoila, M Weinberger, DR AF Heinz, A Jones, DW Mazzanti, C Goldman, D Hommer, D Linnoila, M Weinberger, DR TI Genetic constitution of serotonin transporter affects alcohol neurotoxicity - A beta-CIT SPECT study. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Ruhr Univ Bochum, D-4630 Bochum, Germany. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD USA. NIAAA, NIH, Bethesda, MD 90034 USA. NR 0 TC 0 Z9 0 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 MAY PY 1999 VL 40 IS 5 SU S MA 445 BP 110P EP 110P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800446 ER PT J AU Watabe, H Channing, MA Jousse, F Libutti, SK Carrasquillo, JA Bacharach, SL Carson, RE AF Watabe, H Channing, MA Jousse, F Libutti, SK Carrasquillo, JA Bacharach, SL Carson, RE TI Noninvasive estimation of input function for measurement of tumor blood flow with [O-15]water. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010; Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 2 Z9 2 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 MAY PY 1999 VL 40 IS 5 SU S MA 464 BP 115P EP 115P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800465 ER PT J AU Smith, MF Daube-Witherspoon, ME Plascjak, PS Szajek, LP Carson, RE Everett, JR Green, SL Bacharach, SL Eckelman, WC AF Smith, MF Daube-Witherspoon, ME Plascjak, PS Szajek, LP Carson, RE Everett, JR Green, SL Bacharach, SL Eckelman, WC TI Radioisotope mixture activity estimation and decay correction for Tc-94m PET studies. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 0 Z9 0 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 MAY PY 1999 VL 40 IS 5 SU S MA 472 BP 117P EP 117P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800473 ER PT J AU John, CS Lim, BB Geyer, BC Vilner, BJ Bowen, WD AF John, CS Lim, BB Geyer, BC Vilner, BJ Bowen, WD TI 3-[I-125]iodo-N-[2-(1 '-piperidinyl)ethyl]-N-methyl-4-methoxybenzenesulfonamide, 3-[I-125]PMS: A new sigma receptor binding tumor imaging agent. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 George Washington Univ, Med Ctr, Washington, DC 20037 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 MAY PY 1999 VL 40 IS 5 SU S MA 486 BP 120P EP 120P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800487 ER PT J AU Jousse, F Carrasquillo, JA Libutti, SK Whatley, M Choyke, P Neumann, RD Bacharach, SL AF Jousse, F Carrasquillo, JA Libutti, SK Whatley, M Choyke, P Neumann, RD Bacharach, SL TI Comparison of FDG PET quantitation methods to detect colon cancer metastases. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 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 MAY PY 1999 VL 40 IS 5 SU S MA 565 BP 140P EP 140P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800566 ER PT J AU Kim, MK Jeong, HJ Kao, CHK Yao, TS Kim, IS Waldmann, TA Carrasquillo, JA Paik, CH AF Kim, MK Jeong, HJ Kao, CHK Yao, TS Kim, IS Waldmann, TA Carrasquillo, JA Paik, CH TI Improved tumor targeting of glycolated anti-tac monoclonal antibody Fab fragment labeled with Tc-99m-mercaptoacetyltriglycine (MAG3). SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 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 MAY PY 1999 VL 40 IS 5 SU S MA 1006 BP 226P EP 226P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800921 ER PT J AU Sedelnikova, OA Luu, AN Neumann, RD Panyutin, IG AF Sedelnikova, OA Luu, AN Neumann, RD Panyutin, IG TI A system for detecting DNA double-strand breaks resulting from the action of iodine-125 labeled triplex-forming oligonucleotides. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 MAY PY 1999 VL 40 IS 5 SU S MA 1009 BP 227P EP 227P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800924 ER PT J AU Boerman, OC Eggert, AA Oyen, WJ Scheurs, MW Figdor, CG Corstens, FH Adema, GJ AF Boerman, OC Eggert, AA Oyen, WJ Scheurs, MW Figdor, CG Corstens, FH Adema, GJ TI Dendritic cells labeled with In-111: In vitro and in vivo studies. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Oyen, Wim/D-4178-2009; Adema, G.J./H-8007-2014; Figdor, Carl/A-4232-2010; Boerman, Otto/A-8112-2014 OI Oyen, Wim/0000-0001-8235-7078; Boerman, Otto/0000-0001-6832-101X NR 0 TC 0 Z9 0 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 MAY PY 1999 VL 40 IS 5 SU S MA 1028 BP 231P EP 231P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800943 ER PT J AU Kobayashi, H Tagaya, Y Paik, CH Waldmann, TA Carrasquillo, JA AF Kobayashi, H Tagaya, Y Paik, CH Waldmann, TA Carrasquillo, JA TI Differences of pharmacokinetics and tumor-targeting between radiolabeled interleukin(IL)-15 and IL-2. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Kyoto Univ, Kyoto 606, Japan. NIH, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 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 MAY PY 1999 VL 40 IS 5 SU S MA 1027 BP 231P EP 231P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800942 ER PT J AU Lodge, MA Choyke, P Carrasquillo, JA Libutti, SK Whatley, M Bacharach, SL AF Lodge, MA Choyke, P Carrasquillo, JA Libutti, SK Whatley, M Bacharach, SL TI Correlation of tumor blood flow measured using PET and MRI. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 1 Z9 1 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 MAY PY 1999 VL 40 IS 5 SU S MA 1029 BP 231P EP 231P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800944 ER PT J AU Faries, MB Bedrosian, I Ngyuen, HQ Alavi, A Reynolds, C Scheff, AM Lawton, T Czerniecki, BJ AF Faries, MB Bedrosian, I Ngyuen, HQ Alavi, A Reynolds, C Scheff, AM Lawton, T Czerniecki, BJ TI "Active uptake of macromolecule tracers in sentinel nodes." SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. NCI, Washington, DC USA. NR 0 TC 0 Z9 0 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 MAY PY 1999 VL 40 IS 5 SU S MA 1117 BP 252P EP 252P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105801031 ER PT J AU Heinz, A Williams, W Kerich, M Hommer, D AF Heinz, A Williams, W Kerich, M Hommer, D TI Orbitofrontal glucose utilization is associated with serotonin turnover rate and chronic alcohol intake among male alcoholics and controls. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Ruhr Univ Bochum, D-4630 Bochum, Germany. NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 MAY PY 1999 VL 40 IS 5 SU S MA 1219 BP 276P EP 276P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105801133 ER PT J AU Riddell, CA Brigger, P Libutti, SK Bacharach, SL AF Riddell, CA Brigger, P Libutti, SK Bacharach, SL TI Attenuation correction with the watershed segmentation algorithm for whole-body PET imaging. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 MAY PY 1999 VL 40 IS 5 SU S MA 1297 BP 294P EP 294P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105801210 ER PT J AU Yao, R Seidel, J Johnson, CA Daube-Witherspoon, ME Green, MV Carson, RE AF Yao, R Seidel, J Johnson, CA Daube-Witherspoon, ME Green, MV Carson, RE TI Factors affecting the performance of the 3D OSEM algorithm in the reconstruction of small animal PET images. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, PET Dept, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 0 Z9 0 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 MAY PY 1999 VL 40 IS 5 SU S MA 1321 BP 300P EP 300P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105801234 ER PT J AU Horti, AG Chefer, S Mukhin, AG Koren, AO Links, JM Guendish, D Kurian, V Dannals, RF London, ED AF Horti, AG Chefer, S Mukhin, AG Koren, AO Links, JM Guendish, D Kurian, V Dannals, RF London, ED TI Imaging nicotinic acetylcholine receptors with 6-[F-18]FA, an analog of A-85380 for use with PET. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIDA, Intramural Res Program, Baltimore, MD USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 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 MAY PY 1999 VL 40 IS 5 SU S MA 1349 BP 307P EP 307P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105801262 ER PT J AU Lee, KS Jones, DW Gorey, JG Urbina, RA Raedler, TJ Coppola, RC Rice, KC Weinberger, DR AF Lee, KS Jones, DW Gorey, JG Urbina, RA Raedler, TJ Coppola, RC Rice, KC Weinberger, DR TI In vitro testing of radioligand passage across the blood brain barrier. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 MAY PY 1999 VL 40 IS 5 SU S MA 1348 BP 307P EP 307P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105801261 ER PT J AU Yao, Z Zhang, M Sakahara, H Arano, Y Saji, H Konishi, J AF Yao, Z Zhang, M Sakahara, H Arano, Y Saji, H Konishi, J TI Enhanced accumulation of albumin in intraperitoneal tumors following mannosylation. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. Kyoto Univ, Kyoto 606, Japan. NR 0 TC 0 Z9 0 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 MAY PY 1999 VL 40 IS 5 SU S MA 1371 BP 312P EP 312P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105801284 ER PT J AU Mease, RC Lambert, C McAfee, JG AF Mease, RC Lambert, C McAfee, JG TI Indium-111 CDTA-(aminostyryl)pyridiniumum (Di-X-ASP) dyes: Synthesis, canine and human leukocyte labeling and serum stability. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Univ Maryland, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 MAY PY 1999 VL 40 IS 5 SU S MA 1396 BP 318P EP 318P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105801309 ER PT J AU Karamychev, VN Panyutin, IG Reed, MW Newman, RD AF Karamychev, VN Panyutin, IG Reed, MW Newman, RD TI DNA cleavage by a I-125-labeled minor groove binding agent conjugated to oligodexynucleotides. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Epoch Pharmaceut, Bothell, WA USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 MAY PY 1999 VL 40 IS 5 SU S MA 1405 BP 320P EP 320P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105801318 ER PT J AU Kobayashi, H Kim, IS Drumm, D Kim, MK Paik, DS Le, N Waldmann, TA Carrasquillo, JA Paik, CH AF Kobayashi, H Kim, IS Drumm, D Kim, MK Paik, DS Le, N Waldmann, TA Carrasquillo, JA Paik, CH TI Favorable effects of glycolate conjugation on the biodistribution of humanized antiTac Fab fragment SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE Fab fragment; glycolate; radioimmunodetection; monoclonal antibody ID MONOCLONAL-ANTIBODY FRAGMENTS; STABILIZED FV-IMMUNOTOXINS; RECOMBINANT SINGLE-CHAIN; AMINO-ACID INFUSION; RENAL UPTAKE; NUDE-MICE; INTERLEUKIN-2 RECEPTOR; SOMATOSTATIN ANALOG; T-CELL; CANCER AB One of the major limitations of using intact immunoglobulins for targeting tumors is poor penetration into tissues. Although Fab fragments have been used because of their improved kinetics, they have undesirable high renal accumulation. In this study we tested a new approach to block renal accumulation of Fab. Methods: We conjugated humanized antiTac Fab fragments, which are directed against the interleukin-2 receptor, with glycolate. The biodistribution, pharmacokinetics and catabolism of glycolated Fab (glyco-Fab) were evaluated at two different levels of substitution (heavy and light) compared with nonglycolated Fab in Tac-antigen-positive (ATAC4) and -negative (A431) tumor-bearing nude mice. The mice received coinjections of (125)l-Iabeled glyco-Fab (3 mu Ci/l mu g) and (131)l-labeled nonglycolated Fab (5 mu Ci/1 Gig). In addition, groups of mice receiving these reagents were also coinfused with 50 mg L-lysine. Results: Significantly less glyco-Fab than nonglycolated Fab accumulated in the kidney (21 versus 189 %ID/g; P < 0.001). A higher proportion of glyco-fab was excreted into the urine in its intact form. The glyco-fab survived longer in circulation than nonglycolated Fab. The peak tumor accumulation of glyco-Fab was 2.3-fold greater than that of nonglycolated Fab. Furthermore, the ATAC4 tumor-to-normal tissue ratio of glyco-fab was much higher in all organs than that of nonglycolated Fab. The heavily glyco-Fab accumulated less in the kidney than the lightly glyco-Fab. The coinjected lysine reduced the renal accumulation of both nonglycolated Fab and glyco-Fab. Conclusion: Glyco-Fab is a promising agent because of its lower renal accumulation, higher tumor uptake and higher tumor-to-normal tissue ratio. C1 NCI, Dept Nucl Med, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Carrasquillo, JA (reprint author), NCI, Dept Nucl Med, Warren G Magnuson Clin Ctr, NIH, Bldg 10,Room 1C-496,10 Ctr Dr,MSC 1180, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 40 TC 10 Z9 10 U1 0 U2 2 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 MAY PY 1999 VL 40 IS 5 BP 837 EP 845 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192QD UT WOS:000080089600026 PM 10319759 ER PT J AU Sleasman, JW Nelson, RP Goodenow, MM Wilfret, D Hutson, A Baseler, M Zuckerman, J Pizzo, PA Mueller, BU AF Sleasman, JW Nelson, RP Goodenow, MM Wilfret, D Hutson, A Baseler, M Zuckerman, J Pizzo, PA Mueller, BU TI Immunoreconstitution after ritonavir therapy in children with human immunodeficiency virus infection involves multiple lymphocyte lineages SO JOURNAL OF PEDIATRICS LA English DT Article ID T-CELL DIFFERENTIATION; AGE-RELATED-CHANGES; ANTIRETROVIRAL THERAPY; HIV-1 INFECTION; COMBINATION THERAPY; ACTIVATION; TYPE-1; SUBPOPULATIONS; POPULATION; AIDS AB Objective: To evaluate lymphocyte reconstitution after protease inhibitor therapy in children with human immunodeficiency virus (HIV) infection. Study design: Forty-four HIV-infected children receiving ritonavir monotherapy followed by the addition of zidovudine and didanosine were evaluated during a phase I/II clinical trial. The cohort had a median age of 6.8 years and advanced disease (57% Centers for Disease Control and Prevention stage C, 73% immune stage 3) and was naive to protease inhibitor therapy. Results: After 4 weeks of therapy, there was a significant increase in CD4(+) and CD8(+) T cells. CD4(+) T cells continued to increase, whereas CD8(+) T cells returned to baseline by 24 weeks. Unexpectedly, there was a significant increase in B cells. Changes in CD4(+) T-cell subsets revealed an initial increase in CD4(+) CD45RO T cells followed by a sustained increase in CD4(+) CD45RA T cells. Children <6 years of age had the highest increase in all lymphocyte populations. Significant improvement in CD4(+) T-cell counts was observed even in those children whose viral burden returned to pretherapy levels. Conclusions: Early increases in lymphocytes after ritonavir therapy are a result of recirculation, as shown by increases in B cells and CD4(+) CD45RO and CD8(+) T cells. Children exhibited a high potential to reconstitute CD4(+) CD45RA T cells even with advanced disease and incomplete viral suppression. C1 Univ Florida, Coll Med, Dept Pediat, Div Infect Dis & Immunol, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Dept Pathol & Lab Med, Gainesville, FL 32610 USA. Univ S Florida, All Childrens Hosp, Coll Med, Dept Pediat, St Petersburg, FL 33701 USA. Univ Florida, Dept Stat, Div Biostat, Gainesville, FL USA. Sci Applicat Int Corp Ctr, Frederick, MD USA. NCI, HIV & AIDS Malignancy Branch, Bethesda, MD USA. RP Sleasman, JW (reprint author), Univ Florida, Coll Med, Dept Pediat, Div Infect Dis & Immunol, Box 100296, Gainesville, FL 32610 USA. FU NCRR NIH HHS [RR0082]; NIAID NIH HHS [AI28571]; NICHD NIH HHS [HD 32259] NR 47 TC 63 Z9 63 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 MAY PY 1999 VL 134 IS 5 BP 597 EP 606 DI 10.1016/S0022-3476(99)70247-7 PG 10 WC Pediatrics SC Pediatrics GA 195HM UT WOS:000080244600017 PM 10228296 ER PT J AU Walters, DL Jacobs, DL Tomaszewski, JE Graves, S AF Walters, DL Jacobs, DL Tomaszewski, JE Graves, S TI Analysis of various nucleosides in plasma using solid phase extraction and high-performance liquid chromatography with UV detection SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE nucleoside; HPLC; plasma; analysis; solid phase extraction; antiviral ID 2',3'-DIDEOXYADENOSINE; INFECTIVITY; URINE AB The National Cancer Institute (NCI) has screened many nucleosides for antiviral activity to the HIV-1 virus. Drugs demonstrating antiviral activity are tested in animal models to evaluate their toxicity and pharmacokinetic characteristics. These drugs are subsequently evaluated for efficacy in human clinical trials. Sensitive analytical methodology is needed to quantify nucleosides in plasma and other biological matrices in support of these studies. Battelle has modified and validated a reversed phase high-performance liquid chromatography (HPLC) method for several of these nucleosides that could be easily adapted for similar compounds. Methods have been validated for 6-chloro-2',3'-dideoxyguanosine (6ClddG), 6-chloro-2',3'-dideaxyinosine (6ClddI) and their primary metabolites 2',3'-dideoxyguanosine (ddG) and 2',3'-dideoxyinosine (ddI) in both rat and dog plasma containing EDTA. The method has also been validated for 2'-fluoro-2',3'-dideoxyara-adenosine (beta FlddA) and its primary metabolite 2'-beta-fluorodideoxyinosine (beta FddI) in rat plasma containing heparin. Calibration plasma standards were prepared over ranges of 0.1-10 mu g ml(-1) for beta FlddA and beta FddI, 0.1-50 mu g ml(-1) for 6ClddG and ddG, and 0.25-50 mu g ml(-1) for 6ClddI and ddI in plasma containing 4 mu g ml(-1) pentostatin. The addition of pentostatin to the plasma samples inhibits in-vitro deamination of the drug after collection. Quality control (QC) standards were prepared containing the appropriate anticoagulant and 4 mu g ml(-1) pentostatin at concentrations within each of the bracketed calibration ranges in plasma. These methods have been successfully applied to plasma samples generated during various animal studies. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Battelle Mem Inst, Columbus, OH 43201 USA. NCI, Toxicol & Pharmacol Branch, DTP, DCTDC, Bethesda, MD 20892 USA. RP Walters, DL (reprint author), Battelle Mem Inst, 505 King Ave, Columbus, OH 43201 USA. FU NCI NIH HHS [N01-CM-37834] NR 10 TC 12 Z9 12 U1 1 U2 8 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 MAY PY 1999 VL 19 IS 6 BP 955 EP 965 DI 10.1016/S0731-7085(98)00202-7 PG 11 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 192PU UT WOS:000080088600017 PM 10698562 ER PT J AU Li, P Tabibi, E Yalkowsky, SH AF Li, P Tabibi, E Yalkowsky, SH TI Solubilization of ionized and un-ionized flavopiridol by ethanol and polysorbate 20 SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID COMPLEXATION; CYCLODEXTRINS; COMBINATION; PH AB Because the ionized species is more polar than its unionized counterpart, it is often assumed that the ionized species of the drug does not make a meaningful contribution to solubilization by either cosolvents or surfactants. This report extends previous studies on solubilization of the ionic species by a combination of pH control and complexation to pH control and micellization and to pH control and cosolvency. The total aqueous solubility is expressed as the addition of the concentration of all contributing species: free un-ionized drug [D-u], free ionized drug [D-i], un-ionized drug micelle [DuM], and ionized drug micelle [DiM] for surfactant, and free un-ionized drug [D-u(c)] and free ionized drug [D-i(c)] for cosolvent. The equations indicate that under certain conditions the ionized species can be more important in determining the drug total solubility than the un-ionized species. Flavopiridol, a weak base, is used to test these newly generated equations. As expected, the micellar partition coefficient and solubilization power for ionized flavopiridol are both less than those of the un-ionized species. However, at acidic pH, the solubilities of the ionized drug in surfactant micelles [DiM] and in cosolvent-water [D-i(c)] are both much greater than that of the un-ionized drug. This difference is because the solubilization of the ionized drug is proportional to its aqueous solubility, and its solubility [D-i] can be as much as 24-fold greater than that of the free un-ionized species [D-u]. C1 Univ Arizona, Coll Pharm, Dept Pharmaceut Sci, Tucson, AZ 85721 USA. NCI, Pharmaceut Resources Branch, NIH, Bethesda, MD 20892 USA. RP Yalkowsky, SH (reprint author), Univ Arizona, Coll Pharm, Dept Pharmaceut Sci, Tucson, AZ 85721 USA. FU NCI NIH HHS [N01-CM-27757] NR 8 TC 31 Z9 33 U1 1 U2 8 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD MAY PY 1999 VL 88 IS 5 BP 507 EP 509 DI 10.1021/js980433o PG 3 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 193WX UT WOS:000080161700003 PM 10229640 ER PT J AU Pinsuwan, S Alvarez-Nunez, FA Tabibi, SE Yalkowsky, SH AF Pinsuwan, S Alvarez-Nunez, FA Tabibi, SE Yalkowsky, SH TI Spectrophotometric determination of acidity constants of 4-dedimethylamino sancycline (Col-3), a new antitumor drug SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article AB A spectrophotometric technique was used to determine the acidity constants of 4-dedimethylamino sancycline (Col-3), a new antitumor drug. The apparent pK(a) values of Col-3 in 0.5% methanol aqueous media at approximately 25 degrees C with a constant ionic strength of 0.2 were calculated manually and graphically to be 5.64 +/- 0.17 (pK(a1)) and 8.35 +/- 0.07 (pK(a2)). In addition, the computer program SQUAD was used to confirm Col-3 pK(a) values. The pK(a) values obtained by SQUAD were pK(a1) 5.63 +/- 0.14 and pK(a2) 8.39 +/- 0.04. These results are in agreement with the tetracycline-like structure of Col-3. C1 Univ Arizona, Coll Pharm, Dept Pharmaceut Sci, Tucson, AZ 85721 USA. Prince Songkla Univ, Dept Pharmaceut Technol, Songkhla 90112, Thailand. NCI, NIH, Pharmaceut Resources Branch, Bethesda, MD 20892 USA. RP Yalkowsky, SH (reprint author), Univ Arizona, Coll Pharm, Dept Pharmaceut Sci, Tucson, AZ 85721 USA. FU NCI NIH HHS [CM-77109] NR 8 TC 14 Z9 14 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD MAY PY 1999 VL 88 IS 5 BP 535 EP 537 DI 10.1021/js980398l PG 3 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 193WX UT WOS:000080161700008 PM 10229645 ER PT J AU Witkin, JM Gasior, M Heifets, B Tortella, FC AF Witkin, JM Gasior, M Heifets, B Tortella, FC TI Anticonvulsant efficacy of N-methyl-D-aspartate antagonists against convulsions induced by cocaine SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID NMDA RECEPTOR ANTAGONISTS; DISCRIMINATIVE STIMULUS; BEHAVIORAL PHARMACOLOGY; PHENCYCLIDINE-LIKE; RAT-BRAIN; DIZOCILPINE; SITE; MEMANTINE; TOXICITY; AFFINITY AB Convulsions associated with cocaine abuse can be life threatening and resistant to standard emergency treatment. Cocaine (75 mg/kg, i.p.) produced clonic convulsions in similar to 90% of male, Swiss-Webster mice. A variety of clinically used antiepileptic agents did not significantly protect against cocaine convulsions (e.g., diazepam and phenobarbital). Anticonvulsants in clinical practice that did significantly protect against convulsion did so only at doses with significant sedative/ataxic effects (e.g., clonazepam and valproic acid). In contrast, functional N-methyl-D-aspartate (NMDA) antagonists all produced dose-dependent and significant protection against the convulsant effects of cocaine. Anticonvulsant efficacy was achieved by blockade of both competitive and noncompetitive modulatory sites on the NMDA receptor complex. Thus, competitive antagonists, ion-channel blockers, polyamine antagonists, and functional blockers of the strychnine-insensitive glycine modulatory site all prevented cocaine seizures. The role of NMDA receptors in the control of cocaine-induced convulsions was further strengthened by the positive correlation between the potencies of noncompetitive antagonists or competitive antagonists to block convulsions and their respective affinities for their specific binding sites on the NMDA receptor complex. Although some NMDA blockers produced profound behavioral side effects at efficacious doses (e.g., noncompetitive antagonists), others (e.g., some low-affinity channel blockers, some competitive antagonists, and glycine antagonists) demonstrated significant and favorable separation between their anticonvulsant and side effect profiles. The present results provide the most extensive evidence to date identifying NMDA receptor blockade as a potential strategy for the discovery of agents for clinical use in averting toxic sequelae from cocaine overdose. Given the literature suggesting a role for these drugs in other areas of drug abuse treatments, NMDA receptor antagonists sit in a unique position as potential therapeutic candidates. C1 NIDA, Drug Dev Grp, Behav Neurosci Branch, Addict Res Ctr,NIH, Baltimore, MD 21224 USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Div Neurosci, Dept Neuropharmacol & Mol Biol, Washington, DC 20307 USA. RP Witkin, JM (reprint author), NIDA, Drug Dev Grp, Behav Neurosci Branch, Addict Res Ctr,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 39 TC 33 Z9 33 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 MAY PY 1999 VL 289 IS 2 BP 703 EP 711 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 188PM UT WOS:000079857100013 PM 10215643 ER PT J AU Wei, XX Dai, RK Zhai, SP Thummel, KE Friedman, FK Vestal, RE AF Wei, XX Dai, RK Zhai, SP Thummel, KE Friedman, FK Vestal, RE TI Inhibition of human liver cytochrome P-450 1A2 by the class IB antiarrhythmics mexiletine, lidocaine, and tocainide SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ALKOXYRESORUFIN O-DEALKYLATION; THEOPHYLLINE METABOLISM; RAT-LIVER; MICROSOMES; PROTEINS AB Mexiletine, lidocaine, and tocainide are class IB antiarrhythmic drugs that are used for the treatment of ventricular arrhythmias and are known to inhibit drug metabolism. The objectives of this study were to characterize the inhibitory effects of mexiletine, lidocaine, and tocainide on cytochrome P-450 1A2 (CYP1A2) activity in human liver microsomes and to evaluate their relative inhibitory potencies by using a molecular model of this P-450 isozyme. The inhibitory effect of mexiletine, lidocaine, and tocainide on cytochrome CYP1A2 in human liver microsomes was examined with methoxyresorufin O-demethytase activity as an index of the catalytic activity of this P-450 isozyme. The kinetic inhibition types and K-i values were determined by Lineweaver-Burk plots and Dixon plots, respectively. Molecular modeling was used to assess the interaction of these agents with the CYP1A2 active site. Methoxyresorufin O-demethylase activity was inhibited 67 +/- 8%, 20 +/- 5%, and 7 +/- 4% by 2 mM mexiletine, lidocaine, and tocainide, respectively. Mexiletine and lidocaine exhibited competitive inhibition with K-i values of 0.28 +/- 0.12 mM and 1.54 +/- 0.74 mM, respectively, whereas the inhibition type of tocainide could not be determined because of its weak potency. A charge interaction between mexiletine and the Asp313 side chain in the CYP1A2 active site was found, and varying degrees of hydrogen bond formation between these three compounds and the CYP1A2 active site were observed. The in vitro inhibitory potencies in human liver microsomes (mexiletine > lidocaine > tocainide) are consistent with the structural interactions found in a molecular model of the active site of CYP1A2. C1 Dept Vet Affairs Med Ctr, Clin Pharmacol & Gerontol Res Unit, Boise, ID USA. Mt States Med Res Inst, Boise, ID USA. Idaho State Univ, Dept Pharmaceut Sci, Pocetello, ID USA. NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98195 USA. Univ Washington, Sch Pharm, Dept Pharmaceut, Seattle, WA 98195 USA. RP Vestal, RE (reprint author), Covance Clin & Periapproval Serv Inc, 2121 N Calif Blvd,Suite 500, Walnut Creek, CA 94596 USA. RI Friedman, Fred/D-4208-2016 NR 23 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 1999 VL 289 IS 2 BP 853 EP 858 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 188PM UT WOS:000079857100033 PM 10215663 ER PT J AU Schetz, JA Chu, A Sibley, DR AF Schetz, JA Chu, A Sibley, DR TI Zinc modulates antagonist interactions with D-2-like dopamine receptors through distinct molecular mechanisms SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ENDOGENOUS ZINC; BINDING; RAT; ZN-2+; INHIBITION; RELEASE; BIOLOGY; AGENTS; BRAIN AB Recently, zinc has been shown to modulate antagonist drug interactions with the D-1 dopamine receptor (Schetz and Sibley, 1997) and the dopamine transporter (Norregaard et al., 1998). We now demonstrate that zinc also reversibly and dose-dependently modulates the specific binding of the butyrophenone antagonist [H-3]methylspiperone to all D-2-like dopamine receptors: D-2L, D-3, and D-4. The molecular mechanisms of zinc regulation of these D-2-like receptor subtypes are distinct because zinc inhibition of [H-3]methylspiperone binding to the D-4 receptor is noncompetitive by both equilibrium and kinetic measures (lower B-max and essentially no change in k(off)), whereas the corresponding inhibition of zinc at D-2L and D-3 receptors is primarily characterized by competitive allosterism (increases in K-D and k(off)). Interestingly, thermodynamic measurements reveal that the macroscopic properties of zinc binding are entropy-driven for all receptor subtypes, despite their having distinct molecular mechanisms. Zinc also reduces the binding affinity of the D-2L receptor for [H-3]raclopride, a structurally different antagonist of the substituted benzamide class. Sodium ions negatively modulate zinc inhibition of both sodium-insensitive [H-3]methylspiperone binding and sodium-sensitive [H-3]raclopride binding. In addition to its demonstrated effects on antagonist binding in membrane preparations, zinc also retards the functional effects of antagonist at the D-2L receptor in intact cells. These findings suggest that synaptic zinc may be a factor influencing the effectiveness of therapies that rely on dopamine receptor antagonists. C1 NINDS, Mol Neuropharmacol Sect, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Schetz, JA (reprint author), NINDS, Mol Neuropharmacol Sect, Expt Therapeut Branch, NIH, Bldg 10,Room 5C-108,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 26 TC 43 Z9 44 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 1999 VL 289 IS 2 BP 956 EP 964 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 188PM UT WOS:000079857100045 PM 10215675 ER PT J AU Ghanayem, BI Sanders, JM Chanas, B Burka, LT Gonzalez, FJ AF Ghanayem, BI Sanders, JM Chanas, B Burka, LT Gonzalez, FJ TI Role of cytochrome P-450 2E1 in methacrylonitrile metabolism and disposition SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SPRAGUE-DAWLEY RATS; 2-CYANOETHYLENE OXIDE; ACRYLONITRILE; TOXICITY; INVITRO; MICE; IDENTIFICATION; GLUTATHIONE; EPOXIDATION AB Methacrylonitrile (MAN) is a widely used aliphatic nitrile and is structurally similar to the known rat carcinogen and suspected human carcinogen acrylonitrile (AN). There is evidence that AN is metabolized via the cytochrome P-450 (CYP) 2E1. Recently, we identified two biliary conjugates originating from the interaction of MAN and its epoxide with glutathione. Mercapturic acids formed via the degradation of the two conjugates were also identified in rat and mouse urine. Additionally, a significant portion of MAN was eliminated in the expired air as CO2 (formed via the epoxide pathway) and unchanged MAN. The objective of the present work was to determine whether CYP2E1 is involved in the oxidative metabolism of MAN as was suggested for AN. 2-C-14-MAN was administered to CYP2E1-null or wild-type mice by gavage at 12 mg/kg. Although total urinary and fecal excretion of MAN-derived radioactivity was slightly different in CYP2E1-null versus wild-type mice, the ratio of mercapturic acids originating from the epoxide-glutathione versus MAN-glutathione conjugates were lower in urine of CYP2E1-null mice than in that of wild-type animals. Exhalation of MAN-derived organic volatiles (primarily parent MAN) was 12- and 42-fold greater in female and male CYP2E1-null mice than in wild-type mice, respectively. Additionally, exhalation of CO, derived from metabolism of MAN via the CYP2E1 pathway was 3- to 5-fold greater in wild-type than in CYP2E1-null animals. Although these data indicate that CYP2E1 is the principal enzyme responsible for the oxidative metabolism of MAN, other cytochrome P-450 enzymes may be involved. Assessment of MAN metabolism in CYP2E1-null mice pretreated with 1-aminobenzotriazole (CYP inhibitor) resulted in a further decrease in oxidative metabolites of MAN. Comparison of the tissue concentrations of MAN-derived radioactivity in mouse tissues revealed that MAN-derived radioactivity is generally higher in wild-type > CYP2E1-null mice > CYP2E1-null mice pretreated with 1-aminobenzotriazole, suggesting a direct relationship between MAN oxidative metabolism and the half-life of MAN and/or its metabolites in various tissues. It is therefore concluded that MAN oxidative metabolites such as the epoxide intermediate have greater reactivity than parent MAN. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. NCI, Bethesda, MD 20892 USA. RP Ghanayem, BI (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233,MD B3-10, Res Triangle Pk, NC 27709 USA. NR 25 TC 18 Z9 19 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 1999 VL 289 IS 2 BP 1054 EP 1059 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 188PM UT WOS:000079857100057 PM 10215687 ER PT J AU Masereeuw, R Moons, MM Toomey, BH Russel, FGM Miller, DS AF Masereeuw, R Moons, MM Toomey, BH Russel, FGM Miller, DS TI Active lucifer yellow secretion in renal proximal tubule: Evidence for organic anion transport system crossover SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PERFUSED RAT-KIDNEY; CONJUGATE EXPORT PUMP; ACCUMULATION; CELLS; GENE; INHIBITION; EXPRESSION; MEMBRANE; CATIONS AB Recent studies show that organic anion secretion in renal proximal tubule is mediated by distinct sodium-dependent and sodium-independent transport systems. Here we investigated the possibility that organic anions entering the cells on one system can exit into the lumen on a transporter associated with the other system. In isolated rat kidneys perfused with 10 mu M lucifer yellow (LY, a fluorescent organic anion) plus 100 mu g/ml inulin, the LY-to-inulin clearance ratio averaged 1.6 +/- 0.2, indicating net tubular secretion. Probenecid significantly reduced both LY clearance and LY accumulation in kidney tissue. In intact killifish proximal tubules, confocal microscopy was used to measure steady-state LY uptake into cells and secretion into the tubular lumen. Probenecid, p-aminohippurate, and ouabain nearly abolished both uptake and secretion. To this point, the data indicated that LY was handled by the sodium-dependent and ouabain-sensitive organic anion transport system. However, leukotriene C-4, an inhibitor of the luminal step for the sodium-independent and ouabain-insensitive organic anion system, reduced luminal secretion of LY by 50%. Leukotriene C-4 did not affect cellular accumulation of LY or the transport of fluorescein on the sodium-dependent system. A similar inhibition pattern was found for another fluorescent organic anion, a mercapturic acid derivative of monochlorobimane. Thus, both organic anions entered the cells on the basolateral transporter for the classical, sodium-dependent system, but about half of the transport into the lumen was handled by the luminal carrier for the sodium-independent system, which is most likely the multidrug resistance-associated protein. This is the first demonstration that xenobiotics can enter renal proximal tubule cells on the carrier associated with one organic anion transport system and exit into the tubular lumen on multiple carriers, one of which is associated with a second system. C1 Univ Nijmegen, Fac Med Sci, Dept Pharmacol 233, NL-6500 HB Nijmegen, Netherlands. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC USA. RP Masereeuw, R (reprint author), Univ Nijmegen, Fac Med Sci, Dept Pharmacol 233, POB 9101, NL-6500 HB Nijmegen, Netherlands. RI Russel, Frans/B-3184-2014; Masereeuw, Roos/N-3582-2014; OI Russel, Frans/0000-0002-7959-2314; Masereeuw, Rosalinde/0000-0002-1560-1074 NR 25 TC 28 Z9 29 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 1999 VL 289 IS 2 BP 1104 EP 1111 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 188PM UT WOS:000079857100063 PM 10215693 ER PT J AU Vitiello, B AF Vitiello, B TI Hypericum perforatum extracts as potential antidepressants SO JOURNAL OF PHARMACY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT British Pharmaceutical Conference CY SEP 11, 1998 CL EASTBOURNE, ENGLAND ID PSEUDOHYPERICIN; HYPERFORIN; LI-160; WORT AB Extracts of Hypericum perforatum have been used in the treatment of mild to moderate depression for many years in Europe. More recently, these extracts have become available in the USA as dietary supplements and have been popularly used to improve mood. In support of this practice, data from several controlled clinical studies suggest that Hypericum perforatum is better than placebo and as effective as established antidepressant drugs. These data have, however, several limitations that should temper our enthusiasm and argue for more research before accepting Hypericum perforatum extracts into our pharmacopoeia of established antidepressants. Extant data on the possible effects of Hypericum perforatum extracts in depression are here critically reviewed and plans for further research presented. C1 NIMH, Bethesda, MD 20892 USA. RP Vitiello, B (reprint author), NIMH, Room 7147,6001 Execut Blvd, Bethesda, MD 20892 USA. NR 20 TC 31 Z9 34 U1 0 U2 3 PU ROYAL PHARMACEUTICAL SOC GREAT BRITAIN PI LONDON PA 1 LAMBETH HIGH ST, LONDON SE1 7JN, ENGLAND SN 0022-3573 J9 J PHARM PHARMACOL JI J. Pharm. Pharmacol. PD MAY PY 1999 VL 51 IS 5 BP 513 EP 517 DI 10.1211/0022357991772781 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 209GW UT WOS:000081040700004 PM 10411209 ER PT J AU Agris, PF Marchbank, MT Newman, W Guenther, R Ingram, P Swallow, J Mucha, P Szyk, A Rekowski, P Peletskaya, E Deutscher, SL AF Agris, PF Marchbank, MT Newman, W Guenther, R Ingram, P Swallow, J Mucha, P Szyk, A Rekowski, P Peletskaya, E Deutscher, SL TI Experimental models of protein-RNA interaction: Isolation and analyses of tRNA(Phe) and U1 snRNA-binding peptides from bacteriophage display libraries SO JOURNAL OF PROTEIN CHEMISTRY LA English DT Article DE phage peptide display library; peptide-RNA binding; tRNA; U1 snRNA ID YEAST TRANSFER RNA(PHE); CONFORMATIONAL TRANSITION; ZINC FINGERS; BASE MODIFICATIONS; CRYSTAL-STRUCTURE; DNA ANALOGS; TAR RNA; PHAGE; ANTICODON; RECOGNITION AB Peptides that bind either U1 small nuclear RNA (U1 snRNA) or the anticodon stem and loop of yeast tRNA(Phe) (tRNAP(AC)(Phe)) were selected from a random-sequence, 15-amino acid bacteriophage display library. An experimental system, including an affinity selection method, was designed to identify primary RNA-binding peptide sequences without bias to known amino acid sequences and without incorporating nonspecific binding of the anionic RNA backbone. Nitrocellulose binding assays were used to evaluate the binding of RNA by peptide-displaying bacteriophage. Amino acid sequences of RNA-binding bacteriophage were determined from the foreign insert DNA sequences, and peptides corresponding to the RNA-binding bacteriophage inserts were chemically synthesized. Peptide affinities for the RNAs (K-d approximate to 0.1-5.0 mu M) were analyzed successfully using fluorescence and circular dichroism spectroscopies. These methodologies demonstrate the feasibility of rapidly identifying, isolating, and initiating the analyses of small peptides that bind to RNAs in an effort to define better the chemistry, structure, and function of protein-RNA complexes. C1 N Carolina State Univ, Dept Biochem, Raleigh, NC 27695 USA. Univ Missouri, Dept Biochem, Columbia, MO 65212 USA. Univ Gdansk, Dept Chem, PL-80952 Gdansk, Poland. NCI, Ctr Canc Res, Frederick, MD 21702 USA. RP Agris, PF (reprint author), N Carolina State Univ, Dept Biochem, Box 7622, Raleigh, NC 27695 USA. FU NIGMS NIH HHS [GM-23037, GM-47979] NR 50 TC 18 Z9 18 U1 1 U2 3 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0277-8033 J9 J PROTEIN CHEM JI J. Protein Chem. PD MAY PY 1999 VL 18 IS 4 BP 425 EP 435 DI 10.1023/A:1020688609121 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 221JZ UT WOS:000081725100004 PM 10449040 ER PT J AU Alarcon, GS Tilley, BC Li, SH Fowler, SE Pillemer, SR AF Alarcon, GS Tilley, BC Li, SH Fowler, SE Pillemer, SR CA MIRA Trial Grp TI Self-administered joint counts and standard joint counts in the assessment of rheumatoid arthritis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE joints counts; self-administration; rheumatoid arthritis ID ARTICULAR INDEXES; DISEASE-ACTIVITY; VALIDITY; SENSITIVITY; RELIABILITY AB Objective. To determine the comparability of a text to a mannequin format for the assessment of joint counts (JC) among patients with rheumatoid arthritis (Rh) participating in a randomized clinical trial (RCT). Methods. A subgroup of patients participating in the MIRA (Minocycline in RA) RCT completed self-administered JC and joint scores (JS), which were compared to those of a trained assessor. Results, JC and JS data were consistently higher for the patient than for the assessor. Higher correlations were obtained for JC than for JS. Conclusion. Our data suggest JC can be used in the context of clinical trials or in the clinical setting, but are not interchangeable with trained assessor JC. C1 Univ Alabama, Birmingham, AL 35294 USA. Henry Ford Hlth Sci Ctr, Detroit, MI USA. NIH, Bethesda, MD 20892 USA. RP Alarcon, GS (reprint author), Univ Alabama, UAB Stn,MEB 615,1813 6th Ave S, Birmingham, AL 35294 USA. FU NIAMS NIH HHS [N01-AR-1-2202, N01-AR-1-2204, N01-AR-1-2203] NR 14 TC 11 Z9 12 U1 0 U2 0 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 MAY PY 1999 VL 26 IS 5 BP 1065 EP 1067 PG 3 WC Rheumatology SC Rheumatology GA 191CG UT WOS:000080003200010 PM 10332969 ER PT J AU Lee, YJ AF Lee, YJ TI Biostatistics and clinical trials: a view SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article ID REQUIRING PROLONGED OBSERVATION; DESIGN; PATIENT AB The statistical method is an integral part of clinical trials, because clinical trials are scientific experiments involving human subjects and are to produce objective inferences as to the benefit of intervention - including more narrowly defined medical regiment - under evaluation. Many interventions with reputed anecdotal evidence of plausible benefit turn out to be not so useful if not outright harmful. Furthermore, a treatment good for one group of patients may not be necessarily good for another group of patients receiving a placebo. Clinical trial data are complex and rarely complete. Recently, behavior modifications such as smoking cessation and diet are being evaluated by clinical trial methods. People believed beta-carotene and vitamin C would prevent cancer, but clinical trials have shown no benefit. This points out that the medical plausibility should not be accepted blindly. I will explain the role of statisticians in planning, designing and analyzing clinical trials mainly from my experience. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NIH, Bethesda, MD 20982 USA. NR 18 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD MAY 1 PY 1999 VL 78 IS 1-2 BP 349 EP 367 DI 10.1016/S0378-3758(98)00224-9 PG 19 WC Statistics & Probability SC Mathematics GA 199XR UT WOS:000080509800024 ER PT J AU Grant, BF Hasin, DS AF Grant, BF Hasin, DS TI Suicidal ideation among the United States drinking population: Results from the National Longitudinal Alcohol Epidemiologic Survey SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article ID RISK-FACTORS; SUBSTANCE-ABUSE; HISTORIES; SAMPLE; MEN AB Objective: Data from a national representative sample of adults was used to identify major risk factors of suicidal ideation among the U.S., drinking population. Method: Data from a sample of 18,352 current drinkers, Is years of age and older, were analyzed by means of multiple logistic regression analysis. In these analyses, multivariate associations were examined between risk factors for suicidal ideation and the occurrence of suicidal ideation. Results: For men and women, past year major depression and alcohol dependence were identified as risk factors of suicidal ideation, with major depression having the more sizable impact. Suicidal ideation was increased among men with a past alcohol use disorder, and elevated among women who had used drugs nonmedically and developed a drug use disorder during the past year. The occurrence of a recent physical illness and lifetime treatment for major depression among men and women increased the risk of suicidal ideation, while marriage was protective against ideation for both sexes. Unemployment and having a family history of alcoholism increased the risk of suicidal ideation among men, but not women. Conclusions Major findings are discussed in terms of the impact of severity versus chronicity of psychopathology on suicidal ideation, gender roles and differential engagement in suicidal ideation, and the recognition and treatment of major depression as the single most important intervention in reducing suicidal behavior. C1 NIAAA, Div Biometry & Epidemiol, Bethesda, MD 20892 USA. RP Grant, BF (reprint author), NIAAA, Div Biometry & Epidemiol, Suite 514,6000 Execut Blvd,MSC 7003, Bethesda, MD 20892 USA. NR 36 TC 54 Z9 54 U1 1 U2 2 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD MAY PY 1999 VL 60 IS 3 BP 422 EP 429 PG 8 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 192CC UT WOS:000080059800018 PM 10371272 ER PT J AU Vitiello, B AF Vitiello, B TI High-dose olanzapine in an adolescent - Comment SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Letter C1 NIMH, Rockville, MD 20857 USA. RP Vitiello, B (reprint author), NIMH, Rockville, MD 20857 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 1999 VL 38 IS 5 BP 497 EP 497 DI 10.1097/00004583-199905000-00005 PG 1 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 190HE UT WOS:000079956100005 ER PT J AU Vitiello, B Bhatara, VS Jensen, PS AF Vitiello, B Bhatara, VS Jensen, PS TI Introduction - Current knowledge and unmet needs in pediatric psychopharmacology SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material C1 NIMH, Child & Adolescent Treatment & Prevent Intervent, Bethesda, MD 20892 USA. Univ S Dakota, Dept Psychiat, Sch Med, Sioux Falls, SD USA. RP Vitiello, B (reprint author), NIMH, Child & Adolescent Treatment & Prevent Intervent, Room 7149,6001 Execut Blvd, Bethesda, MD 20892 USA. NR 10 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 1999 VL 38 IS 5 BP 501 EP 502 DI 10.1097/00004583-199905000-00010 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 190HE UT WOS:000079956100010 ER PT J AU Emslie, GJ Walkup, JT Pliszka, SR Ernst, M AF Emslie, GJ Walkup, JT Pliszka, SR Ernst, M TI Nontricyclic antidepressants: Current trends in children and adolescents SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Review DE selective serotonin reuptake inhibitors; monoamine oxidase inhibitors; psychopharmacology; safety; efficacy ID OBSESSIVE-COMPULSIVE DISORDER; ATTENTION-DEFICIT DISORDER; MONOAMINE-OXIDASE INHIBITORS; PRELIMINARY CLINICAL-EXPERIENCE; OPEN-LABEL TRIAL; MAJOR DEPRESSION; FLUOXETINE TREATMENT; DOUBLE-BLIND; HYPERACTIVITY DISORDER; TRICYCLIC ANTIDEPRESSANTS AB Objectives: First, to review the extant data on the safety and efficacy of the use of nontricyclic antidepressants in children and adolescents; second, to identify the main limitations of our current knowledge in this area; and third, to point to future research directions. Method: A Medline search and a review of previous scientific meetings were conducted; all available reports on the efficacy and safety of nontricyclic antidepressants in children and adolescents were critically reviewed. Results: As in adults, also in children nontricyclic antidepressants are potentially useful in treating a variety of psychiatric disorders. The data supporting their efficacy, however, are quite limited. Obsessive-compulsive disorder is the only psychiatric diagnosis for which pediatric use of selective serotonin reuptake inhibitors has been approved. One placebo-controlled study in children and adolescents with major depression supports the efficacy of fluoxetine. Other clinical trials of nontricyclic antidepressants in depressed adolescents are in progress. Available data indicate that the safety of these medications is good, at least in the short term. Conclusions: The potential usefulness of nontricyclic antidepressants for children and adolescents suffering from a range of disorders is considerable. While information from adults can suggest potential areas of possible efficacy in pediatric patients suffering from similar psychopathology, further research is essential to provide the necessary information on the efficacy, safety, and pharmacokinetics of these medications in children and adolescents. C1 Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75235 USA. Johns Hopkins Med Inst, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. NIDA, Brain Imaging Ctr, NIH, Baltimore, MD USA. RP Emslie, GJ (reprint author), Univ Texas, SW Med Ctr, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75235 USA. FU NIMH NIH HHS [K20 MH D1058, MH-39188] NR 117 TC 70 Z9 71 U1 6 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 1999 VL 38 IS 5 BP 517 EP 528 DI 10.1097/00004583-199905000-00013 PG 12 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 190HE UT WOS:000079956100013 PM 10230183 ER PT J AU Campbell, M Rapoport, JL Simpson, GM AF Campbell, M Rapoport, JL Simpson, GM TI Antipsychotics in children and adolescents SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE antipsychotics; efficacy; safety; review ID NEUROLEPTIC-RELATED DYSKINESIAS; CHILDHOOD-ONSET SCHIZOPHRENIA; INTELLECTUALLY SUBAVERAGE CHILDREN; PERVASIVE DEVELOPMENTAL DISORDER; AUTISTIC-CHILDREN; TARDIVE-DYSKINESIA; TOURETTES DISORDER; RATING-SCALE; RISPERIDONE TREATMENT; AGGRESSIVE-CHILDREN AB Objectives: To present a critical overview of the available evidence for the efficacy and safety of antipsychotic agents in children and adolescents and to identify knowledge gaps and needs for further research. Data from adults that are relevant to children are discussed. Method: Mainly reports of double-blind, placebo-controlled studies were reviewed. Results: In children and adolescents, antipsychotics are used to treat psychotic and a variety of nonpsychotic conditions. The amount of data based on well-designed, double-blind, placebo-controlled studies with satisfactory sample sizes in diagnostically homogeneous subjects is modest. Conclusions: Currently available standard antipsychotics have a definite role in the treatment of children and adolescents. The use of these agents is limited mainly by tardive and withdrawal dyskinesias and, in same patients, by excessive sedation. The atypical antipsychotics should be critically assessed and compared with psychosocial interventions; it effective, the combination of both types of treatments should be evaluated. C1 NYU, Med Ctr, Dept Psychiat, New York, NY 10016 USA. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. Univ So Calif, Dept Psychiat & Behav Sci, Los Angeles, CA USA. RP Campbell, M (reprint author), NYU, Med Ctr, Dept Psychiat, 550 1st Ave, New York, NY 10016 USA. FU NIMH NIH HHS [MH-40177, MH-18915] NR 87 TC 61 Z9 63 U1 4 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 1999 VL 38 IS 5 BP 537 EP 545 DI 10.1097/00004583-199905000-00015 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 190HE UT WOS:000079956100015 PM 10230185 ER PT J AU Jensen, PS Bhatara, VS Vitiello, B Hoagwood, K Feil, M Burke, LB AF Jensen, PS Bhatara, VS Vitiello, B Hoagwood, K Feil, M Burke, LB TI Psychoactive medication prescribing practices for US children: Gaps between research and clinical practice SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE pharmacoepidemiology; psychopharmacology; medication safety and efficacy; childhood mental disorders; prescribing practices ID CARBAMAZEPINE-INDUCED MANIA; PSYCHOPHARMACOLOGY; PSYCHIATRISTS; PRESCRIPTION; ADHD AB Objective: To determine national pediatric prescribing practices for psychotropic agents and to examine these practices in view of the available evidence concerning their safety and efficacy in this age group. Method: Prescribing data from 2 national databases based on surveys of office-based medical practices were determined and reviewed vis-g-vis available safety and efficacy evidence. Results: Data indicate that levels of psychotropic prescribing in children and adolescents are greatest for stimulants, resulting in nearly 2 million office visits and 6 million drug "mentions" in 1995. Selective serotonin reuptake inhibitors were the second most prescribed psychotropic agents, while anticonvulsant mood stabilizers (prescribed for a psychiatric reason), tricyclic antidepressants, central adrenergic agonists, antipsychotics, benzodiazepines, and lithium were also prescribed for a substantial number of office visits. Comparison of prescribing frequencies with available safety and efficacy data indicates significant gaps in knowledge for commonly used agents. Conclusions: Most psychotropic agents require further sustained study to ensure appropriate health care expenditures and vouchsafe children's safety. Recommendations for researchers, parents, federal agencies, and industry are offered as a means to accelerate the pace of research progress. C1 NIMH, Child & Adolescent Treatment & Prevent Intervent, Bethesda, MD 20892 USA. Univ S Dakota, Sch Med, Sioux Falls, SD USA. NIMH, Child Serv Program, Serv Res Branch, Bethesda, MD 20892 USA. NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. RP Jensen, PS (reprint author), NIMH, Child & Adolescent Treatment & Prevent Intervent, 6001 Execut Blvd,Room 8223,MSC 9669, Bethesda, MD 20892 USA. OI Jensen, Peter/0000-0003-2387-0650 NR 46 TC 166 Z9 168 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 1999 VL 38 IS 5 BP 557 EP 565 DI 10.1097/00004583-199905000-00017 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 190HE UT WOS:000079956100017 PM 10230187 ER PT J AU Merz, CNB Kelsey, SF Pepine, CJ Reichek, N Reis, SE Rogers, WJ Sharaf, BL Sopko, G AF Merz, CNB Kelsey, SF Pepine, CJ Reichek, N Reis, SE Rogers, WJ Sharaf, BL Sopko, G CA WISE Study Grp TI The Women's Ischemia Syndrome Evaluation (WISE) study: Protocol design, methodology and feasibility report SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; MYOCARDIAL-INFARCTION; HEART-DISEASE; POSTMENOPAUSAL WOMEN; BYPASS-SURGERY; N-13 AMMONIA; RISK-FACTORS; BLOOD-FLOW; PILOT ACIP; EXERCISE AB OBJECTIVES The Women's Ischemia Syndrome Evaluation (WISE) is a National Heart, Lung and Blood Institute-sponsored four-center study designed to: 1) optimize symptom evaluation and diagnostic testing for ischemic heart disease; 2) explore mechanisms for symptoms and myocardial ischemia in the absence of epicardial corollary artery stenoses, and 3) evaluate the influence of reproductive hormones on symptoms and diagnostic test response. BACKGROUND Accurate diagnosis of ischemic heart disease in women is a major challenge to physicians, and the role reproductive hormones play in this diagnostic uncertainty is unexplored. Moreover, the significance and pathophysiology of ischemia in the absence of significant epicardial coronary stenoses is unknown. METHODS The WISE common core data include demographic and clinical data, symptom and psychosocial variables, coronary angiographic and ventriculographic data, brachial artery reactivity testing, resting/ambulatory electrocardiographic monitoring and a variety of blood determinations Site-specific complementary methods include physiologic and functional cardiovascular assessments of myocardial perfusion and metabolism, ventriculography, endothelial vascular function and coronary angiography. Women are followed for at least 1 year to assess clinical events and symptom status. RESULTS In Phase I (1996-1997), a pilot phase, 256 women were studied. These data indicate that the WISE protocol is safe and feasible for identifying symptomatic women with and without significant epicardial coronary artery stenoses. CONCLUSIONS The WISE study will define contemporary diagnostic testing to evaluate women with suspected ischemic heart disease. Phase II (1997-1999) is ongoing and will study an additional 680 women, for a total WISE enrollment of 936 women. Phase III (2000) will include patient follow-up, data analysis and a National Institutes of Health WISE workshop. (C) 1999 by the American College of Cardiology. C1 Cedars Sinai Med Ctr, Cedars Sinai Res Inst, Dept Med, Div Cardiol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. Univ Florida, Dept Med, Div Cardiol, Gainesville, FL 32611 USA. Allegheny Gen Hosp, Div Cardiol, Dept Med, MCP Hahnemann Sch Med, Pittsburgh, PA 15212 USA. Univ Pittsburgh, Div Cardiol, Dept Med, Pittsburgh, PA 15260 USA. Univ Alabama, Dept Med, Div Cardiol, Birmingham, AL 35294 USA. Rhode Isl Hosp, Providence, RI 02903 USA. NHLBI, Div Heart & Vasc Dis, NIH, Bethesda, MD 20892 USA. RP Merz, CNB (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Wise Coordinating Ctr, 127 Parran Hall,130 DeSoto St, Pittsburgh, PA 15261 USA. RI Reis, Steven/J-3957-2014 FU NHLBI NIH HHS [N01-HV-68163, N01-HV-68162, N01-HV-68161] NR 43 TC 170 Z9 174 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY PY 1999 VL 33 IS 6 BP 1453 EP 1461 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 210UH UT WOS:000081122700004 PM 10334408 ER PT J AU Lewis, JF Lin, L McGorray, S Pepine, CJ Doyle, M Edmundowicz, D Holubkov, R Pohost, G Reichek, N Rogers, W Sharaf, BL Sopko, G Merz, CNB AF Lewis, JF Lin, L McGorray, S Pepine, CJ Doyle, M Edmundowicz, D Holubkov, R Pohost, G Reichek, N Rogers, W Sharaf, BL Sopko, G Merz, CNB TI Dobutamine stress echocardiography in women with chest pain - Pilot phase data from the National Heart, Lung and Blood Institute Women's Ischemia Syndrome Evaluation (WISE) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; EMISSION COMPUTED-TOMOGRAPHY; MYOCARDIAL-INFARCTION; GENDER DIFFERENCES; EXERCISE; DIPYRIDAMOLE; DIAGNOSIS; ACCURACY; ANGIOGRAPHY; PREVALENCE AB OBJECTIVES The aim of this project was to assess the utility of dobutamine stress echocardiography (DSE) for evaluation of women with suspected ischemic heart disease. BACKGROUND Most investigations addressing efficacy of diagnosis and treatment of coronary artery disease (CAD) have been performed in predominantly male populations. As part of the Women's Ischemia Syndrome Evaluation (WISE) study, DSE was assessed in women participating at the University of Florida clinical site. METHODS Women with chest pain or other symptoms suggestive of myocardial ischemia and clinically indicated coronary angiography were eligible for the WISE study. Enrolled subjects underwent DSE using a modified protocol. Coronary stenosis was assessed by core laboratory quantitative coronary angiography (QCA). RESULTS The 92 women studied ranged in age from 34 to 82 years (mean 57.5). All women had greater than or equal to 1 major risk for CAD, and most (89, 97%) had greater than or equal to 2 risk factors. In 78 women (85%), left ventricular wall motion was normal at baseline and during peak infusion. The remaining 14 women had wall motion abnormalities during DSE. By QCA, 25 women (27%) had greater than or equal to 50% coronary stenosis, including 10 with single-vessel obstruction. Dobutamine stress echocardiopraphy was abnormal in 10:of these 25 women, yielding overall sensitivity of 40%, and 60% for multivessel stenosis. Exclusion of women with inadequate heart rate response yielded overall sensitivity of 50%, and 81.8% for multivessel stenosis. Dobutamine stress echocardiography was normal in 54 of the 67 women with <50% coronary narrowing, specificity 80.6%. CONCLUSIONS Dobutamine stress echocardiography reliably detects multivessel stenosis in women with suspected CAD. However, DSE is usually negative in women with single-vessel stenosis, and in the larger subset without coronary stenosis. Ongoing protocols of the WISE study are expected to improve diagnostic accuracy in women with single-vessel disease, as well as provide important data in the substantial number of women with chest pain but without epicardial coronary artery stenosis. (C) 1999 by the American College of Cardiology. C1 Univ Florida, Wise Clin Ctr, Div Cardiol, Gainesville, FL 32611 USA. Univ Alabama Birmingham, Div Cardiol, Birmingham, AL USA. Univ Pittsburgh, Div Cardiol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Wise Coordinating Ctr, Pittsburgh, PA 15260 USA. Allegheny Univ, Ctr Hlth, Div Cardiol, Pittsburgh, PA USA. NHLBI, Bethesda, MD USA. Cedars Sinai Med Ctr, Los Angeles, CA USA. Brown Univ, Providence, RI 02912 USA. RP Lewis, JF (reprint author), Univ Pittsburgh, WISE Coordinating Ctr, 127 Parran Hall,130 DeSoto St, Pittsburgh, PA 15261 USA. FU NHLBI NIH HHS [N01-HV-68162, N01-HV-68161, N01-HV-68163] NR 33 TC 53 Z9 54 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY PY 1999 VL 33 IS 6 BP 1462 EP 1468 DI 10.1016/S0735-1097(99)00076-5 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 210UH UT WOS:000081122700005 PM 10334409 ER PT J AU Reis, SE Holubkov, R Lee, JS Sharaf, B Reichek, N Rogers, WJ Walsh, EG Fuisz, AR Kerensky, R Detre, KM Sopko, G Pepine, CJ AF Reis, SE Holubkov, R Lee, JS Sharaf, B Reichek, N Rogers, WJ Walsh, EG Fuisz, AR Kerensky, R Detre, KM Sopko, G Pepine, CJ CA WISE Investigators TI Coronary flow velocity response to adenosine characterizes coronary microvascular function in women with chest pain and no obstructive coronary disease - Results from the pilot phase of the Women's Ischemia Syndrome Evaluation (WISE) study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID TERM FOLLOW-UP; ANGINA-PECTORIS; SYNDROME-X; BLOOD-FLOW; MYOCARDIAL PERFUSION; VASODILATOR RESERVE; ARTERY DISEASE; ATHEROSCLEROSIS; ARTERIOGRAMS; VALIDATION AB OBJECTIVES We sought to develop and validate a definition of coronary microvascular dysfunction in women with chest pain and no significant epicardial obstruction based on adenosine-induced changes in coronary flow velocity (i.e., coronary velocity reserve). BACKGROUND Chest pain is frequently not caused by fixed obstructive coronary artery disease (CAD) of of large vessels in women. Coronary microvascular dysfunction is an alternative mechanism or chest pain that is more prevalent in women and is associated with attenuated coronary volumetric flow augmentation in response to hyperemic stimuli (i.e., abnormal coronary flow reserve). However, traditional assessment of coronary volumetric flow reserve is time consuming and not uniformly available. METHODS As part of the Women's Ischemia Syndrome Evaluation (WISE) study, 48 women with chest pam and normal coronary arteries or minimal coronary luminal irregularities (mean stenosis = 7%) underwent assessment of coronary blood flow reserve and coronary flow velocity reserve. Blood flow responses to intracoronary adenosine were measured using intracoronary Doppler ultrasonography and quantitative angiography RESULTS Coronary volumetric flow reserve correlated with coronary velocity reserve (Pearson correlation = 0.87, p < 0.001). In 29 (60%) women with abnormal coronary microcirculation (mem coronary flow reserve = 1.84), adenosine increased coronary velocity by 89% (p < 0.001) but did not change coronary cross-sectional area. In 19 (40%) women with normal microcirculation (mean flow reserve = 3.24), adenosine increased coronary velocity and area by 179% (p < 0.001) and 17% (p < 0.001), respectively. A coronary velocity reserve threshold of 2.24 provided the best balance between sensitivity and specificity (90% and 89%, respectively) for the diagnosis of microvascular dysfunction. In addition, failure of the epicardial coronary to dilate at least 9% was found to be a sensitive (79%) and specific (79%) surrogate marker of microvascular dysfunction CONCLUSIONS Coronary flow velocity response to intracoronary adenosine characterizes coronary microvascular function in women with chest pain in the absence of obstructive CAD. Attenuated epicardial coronary dilation response to adenosine may be a surrogate marker of microvascular dysfunction in women with chest pain and no obstructive CAD. (C) 1999 by the American College of Cardiology. C1 Univ Pittsburgh, Div Cardiol, Dept Med, Pittsburgh, PA 15260 USA. Rhode Isl Hosp, Div Cardiol, Dept Med, Providence, RI 02903 USA. Allegheny Univ Hlth Sci, Div Cardiol, Dept Med, Pittsburgh, PA USA. Univ Alabama, Dept Med, Div Cardiol, Birmingham, AL 35294 USA. Univ Florida, Dept Med, Div Cardiol, Gainesville, FL 32611 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. NHLBI, Div Heart & Vasc Dis, Bethesda, MD 20892 USA. RP Reis, SE (reprint author), WISE Coordinating Ctr, 127 Parran Hall,130 DeSoto St, Pittsburgh, PA 15261 USA. RI Reis, Steven/J-3957-2014 FU NHLBI NIH HHS [N01-HV-68161, N01-HV-68163, N01-HV-68162] NR 27 TC 91 Z9 100 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY PY 1999 VL 33 IS 6 BP 1469 EP 1475 DI 10.1016/S0735-1097(99)00072-8 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 210UH UT WOS:000081122700006 PM 10334410 ER PT J AU Stone, PH Krantz, DS McMahon, RP Goldberg, AD Becker, LC Chaitman, BR Taylor, HA Cohen, JD Freedland, KE Bertolet, BD Coughlan, C Pepine, CJ Kaufmann, PG Sheps, DS AF Stone, PH Krantz, DS McMahon, RP Goldberg, AD Becker, LC Chaitman, BR Taylor, HA Cohen, JD Freedland, KE Bertolet, BD Coughlan, C Pepine, CJ Kaufmann, PG Sheps, DS CA PIMI Study Grp TI Relationship among mental stress-induced ischemia and ischemia during daily life and during exercise: The psychophysiologic investigations of myocardial ischemia (PIMI) study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; LEFT-VENTRICULAR DYSFUNCTION; AMBULATORY ISCHEMIA; INFARCTION; RESPONSES; INDUCTION; FREQUENCY; TRIGGERS; ANGER; DEATH AB OBJECTIVES The purposes of this database study were to determine: 1) the relationship between mental stress-induced ischemia and ischemia during daily life and during exercise; 2) whether patients who exhibited daily life ischemia experienced greater hemodynamic and catecholamine responses to mental or physical stress than patients who did not exhibit daily life ischemia, and 3) whether patients who experienced daily life ischemia could be identified on :the basis of laboratory-induced ischemia using mental or exercise stress testing. BACKGROUND The relationships between mental stress-induced ischemia in the laboratory and ischemia during daily life and during exercise are unclear. METHODS One hundred ninety-six stable patients with documented coronary disease and a positive exercise test underwent mental stress testing and bicycle exercise testing. Radionuclide ventriculography and electrocardiographic (ECC) were performed during the mental stress and bicycle tests. Patients underwent 48 h of ambulatory ECC monitoring Hemodynamic and catecholamine responses were obtained during mental stress and bicycle tests. RESULTS Ischemia (reversible left ventricular dysfunction or ST segment depression greater than or equal to 1 mm) developed in 106 of 183 patients (58%) during the mental stress test. There were no significant differences in clinical characteristics of patients with, compared with those without, mental stress-induced ischemia. Patients with mental stress ischemia more often had daily Life ischemia than patients without mental stress ischemia, but their exercise tests were similar. Patients with daily life ischemia had higher ejection fraction and cardiac output, and lower systemic vascular resistance during mental stress than patients without daily life ischemia. Blood pressure and catecholamine levels at rest and during the mental stress tests were not different in patients with, compared with those without, daily life ischemia. Patients with daily life ischemia had a higher ejection fraction at rest and at peak bicycle exercise compared with patients without daily life ischemia, but were were no other differences in peak hemodynamic or catecholamine responses to exercise. The presence of ST segment depression during routine daily activities was best predicted by ST segment depression during mental or bicycle exercise stress, although ST segment depression was rare during mental stress. CONCLUSIONS Patients with daily life ischemia exhibit a heightened generalized response to mental stress. ST segment depression in response to mental or exercise stress is more predictive of ST segment depression during routine daily activities than other laboratory-based ischemic maskers. Therapeutic management strategies might therefore focus on patients with these physiologic responses to stress and on whether lessening such responses reduces ischemia. (C) 1999 by the American College of Cardiology. C1 Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Maryland Med Res Inst, PIMI Clin Coordinating Ctr, Baltimore, MD 21210 USA. Harvard Univ, Boston, MA 02115 USA. Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD USA. Maryland Med Res Inst, Baltimore, MD USA. Henry Ford Hosp, Div Cardiol, Detroit, MI 48202 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. St Louis Univ, Div Cardiol, St Louis, MO 63103 USA. St Louis Univ, Hlth Sci Ctr, St Louis, MO 63103 USA. Univ Alabama, Med Ctr, Div Cardiol, Birmingham, AL 35294 USA. Univ Florida, Hlth Sci Ctr, Gainesville, FL 32611 USA. NHLBI, Bethesda, MD 20892 USA. E Tennessee State Univ, James H Quillen Coll Med, Div Cardiol, Johnson City, TN 37614 USA. Jackson Med Mall, Milwaukee, WI USA. Washington Univ, St Louis, MO 63130 USA. RP Stone, PH (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. RI McMahon, Robert/C-5462-2009; Krantz, David/L-5364-2015 OI Krantz, David/0000-0002-1671-1355 FU NHLBI NIH HHS [HV18119, HV18114, HV18121] NR 38 TC 34 Z9 34 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY PY 1999 VL 33 IS 6 BP 1476 EP 1484 DI 10.1016/S0735-1097(99)00075-3 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 210UH UT WOS:000081122700007 PM 10334411 ER PT J AU Bourassa, MG Kip, KE Jacobs, AK Jones, RH Sopko, G Rosen, AD Sharaf, BL Schwartz, L Chaitman, BR Alderman, EL Holmes, DR Roubin, GS Detre, KM Frye, RL AF Bourassa, MG Kip, KE Jacobs, AK Jones, RH Sopko, G Rosen, AD Sharaf, BL Schwartz, L Chaitman, BR Alderman, EL Holmes, DR Roubin, GS Detre, KM Frye, RL CA BARI Investigators TI Is a strategy of intended incomplete percutaneous transluminal coronary angioplasty revascularization acceptable in nondiabetic patients who are candidates for coronary artery bypass graft surgery? The Bypass Angioplasty Revascularization Investigation (BARI) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID RANDOMIZED TRIAL; FOLLOW-UP; MYOCARDIAL REVASCULARIZATION; DISEASE; SURVIVAL; REGISTRY; COMPLETENESS; DETERMINANTS; INFARCTION; OPERATION AB OBJECTIVES Our objective was to determine whether a strategy of intended incomplete percutaneous transluminal coronary angioplasty revascularization (IR) compromises long-term patient outcome. BACKGROUND Complete angioplasty revascularization (CR) is often not planned nor attempted in patients with multivessel coronary disease, and the extent to which this influences outcome is unclear. METHODS Before randomization, in the Bypass Angioplasty Revascularization Investigation, all angiograms were assessed for intended CR or IR via angioplasty. Outcomes were compared among patients with IR intended if assigned to angioplasty, randomized to coronary artery bypass graft surgery (CABG) versus angioplasty; and within angioplasty patients only, among patients with IR versus CR intended. RESULTS At 5 years, there was a trend for higher overall (88.6% vs. 84.0%) and cardiac survival (94.5% vs. 92.1%) in CABG versus angioplasty patients with IR intended. The excess mortality in angioplasty patients occurred solely in diabetic subjects; overall and cardiac survival were similar among nondiabetic CABG and angioplasty patients. Freedom from myocardial infarction (MI) at 5 years was higher in nondiabetic CABG versus angioplasty patients (92.4% vs. 85.2%, p = 0.02), yet was similar to the rate observed (85%) in nondiabetic CABG and angioplasty patients with CR intended. Five-year rates of death, cardiac death, repeat revascularization and angina were similar in all angioplasty patients with IR versus CR intended. However, a trend for greater freedom from subsequent CABG was seen in CR patients (70.3% vs. 64.0%, p = 0.08). CONCLUSIONS Intended incomplete angioplasty revascularization in nondiabetic patients with multivessel disease who are candidates for both angioplasty and CABG does not compromise long-term survival; however, subsequent need for CABG may be increased with this strategy. Whether the risk of long-term MI is also increased remains uncertain. (C) 1999 by the American College of Cardiology. C1 Montreal Heart Inst, Res Ctr, Dept Med, Montreal, PQ H1T 1C8, Canada. Univ Pittsburgh, Pittsburgh, PA USA. Boston Med Ctr, Boston, MA USA. Duke Univ, Med Ctr, Durham, NC USA. NHLBI, Bethesda, MD 20892 USA. Rhode Isl Hosp, Providence, RI USA. Toronto Hosp, Toronto, ON M5T 2S8, Canada. St Louis Hosp, St Louis, MO USA. Stanford Univ, Med Ctr, Palo Alto, CA USA. Mayo Clin, Rochester, MN USA. Lenox Hill Hosp, New York, NY 10021 USA. RP Bourassa, MG (reprint author), Montreal Heart Inst, Res Ctr, Dept Med, 5000 Belanger St E, Montreal, PQ H1T 1C8, Canada. OI Bourassa, Martial G./0000-0002-4439-8650 FU NHLBI NIH HHS [HL38493, HL38504, HL38509] NR 32 TC 39 Z9 39 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY PY 1999 VL 33 IS 6 BP 1627 EP 1636 DI 10.1016/S0735-1097(99)00077-7 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 210UH UT WOS:000081122700030 PM 10334434 ER PT J AU Slavkin, HC AF Slavkin, HC TI Changing patterns of disease and mucosal immunity SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article C1 NIDCR, Bethesda, MD 20892 USA. RP Slavkin, HC (reprint author), NIDCR, 31 Ctr Dr,MSC 2290,Bldg 31,Room 2C39, Bethesda, MD 20892 USA. NR 16 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 MAY PY 1999 VL 130 IS 5 BP 735 EP 738 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 194PX UT WOS:000080203700024 PM 10332139 ER PT J AU Field, TS Gurwitz, JH Glynn, RJ Salive, ME Gaziano, JM Taylor, JO Hennekens, CH AF Field, TS Gurwitz, JH Glynn, RJ Salive, ME Gaziano, JM Taylor, JO Hennekens, CH TI The renal effects of nonsteroidal anti-inflammatory drugs in older people: Findings from the established populations for epidemiologic studies of the elderly SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE NSAIDs; renal function; serum creatinine; older people ID ANTIINFLAMMATORY DRUGS; SERUM CREATININE; INDEPENDENT PREDICTOR; DISEASE; IBUPROFEN; FAILURE; RISK; MORTALITY; SULINDAC; ASPIRIN AB OBJECTIVE: To determine whether older people who use nonsteroidal anti-inflammatory agents (NSAIDs) have increased levels of blood urea nitrogen (BUN), serum creatinine, and BUN:serum creatinine ratio. DESIGN: Cross-sectional, secondary data analysis. SETTING: Older people living in the communities of East Boston, MA, New Haven, CT, and Washington and Iowa Counties, Iowa. PARTICIPANTS: A total of 4099 people aged 70 years or older who were participants in the National Institute on Aging's Established Populations for Epidemiologic Studies of the Elderly project, had survived to the 6-year follow-up interview and had consented to the blood drawing. MEASUREMENTS: We assessed use of the NSAIDs at the 3- and h-year interviews through a drug inventory and visual review of medication containers. Markers of renal function assessed through analysis of blood samples drawn at the time of the interview included BUN and creatinine. RESULTS: Fifteen percent of the cohort reported use of NSAIDs during the 2 weeks preceding the 6-year interview. Controlling for age, sex, and a range of potential confounding variables, NSAID users had significant prevalence odds ratios of 1.9 (95% confidence interval (CI), 1.5-2.3) for being in the highest quartile of BUN (>23), 1.3 (CI 1.1-1.7) for the highest quartile of serum creatinine (greater than or equal to 1.4), and 1.7 (CI 1.4-2.1) for the highest quartile of the BUN:creatinine ratio (greater than or equal to 19.4). Chronic NSAID users (those who reported NSAID use at both the 3-year and 6-year interviews) accounted for the increased risk of high serum creatinine levels. CONCLUSION: Community-dwelling older people who use NSAIDs tend to have higher levels of common laboratory markers of renal dysfunction. This hypothesis requires further testing in prospective cohort studies designed a priori to evaluate these issues. C1 Meyers Primary Care Inst, Worcester, MA 01608 USA. Univ Massachusetts, Sch Med, Worcester, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NIA, NIH, Bethesda, MD 20892 USA. Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. E Boston Neighborhood Hlth Ctr, Boston, MA USA. RP Field, TS (reprint author), Meyers Primary Care Inst, 100 Cent St, Worcester, MA 01608 USA. FU NIA NIH HHS [AG02107, 5 T32 AG00158] NR 38 TC 23 Z9 23 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 1999 VL 47 IS 5 BP 507 EP 511 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 194NU UT WOS:000080201100001 PM 10323640 ER PT J AU Foley, DJ Monjan, AA Masaki, KH Enright, PL Quan, SF White, LR AF Foley, DJ Monjan, AA Masaki, KH Enright, PL Quan, SF White, LR TI Associations of symptoms of sleep apnea with cardiovascular disease, cognitive impairment, and mortality among older Japanese-American men SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT 16th Congress of the International-Association-of-Gerontology CY AUG 16-18, 1997 CL HONOLULU, HAWAII SP Int Assoc Gerontol DE sleep apnea; snoring; daytime sleepiness; mortality; cognitive impairment; cardiovascular disease ID DAYTIME SLEEPINESS; RISK FACTOR; POPULATION; ADULTS; DISTURBANCES; PREVALENCE; HEALTH; INFARCTION; DEMENTIA; HAWAII AB OBJECTIVES: To examine the association between symptoms of sleep apnea and prevalent cardiovascular disease, cognitive impairment, and subsequent 3-year mortality. DESIGN: A longitudinal study. SETTING: Participants lived in the community on Oahu, Hawaii PARTICIPANTS: A total of 2905 older Japanese-American men participating in the fourth examination of the Honolulu Heart Program cohort study from 1991-1993, which is the baseline for the Honolulu-Asia Aging Study of dementia. MEASUREMENTS: Self-reported snoring, daytime sleepiness, and breathing pauses; diagnosed cardiovascular disease and dementia; cognitive functioning and vital status approximately 3 years later. RESULTS: More than 12% of the participants reported that they often or always snored loudly, and 8% reported being sleepy most of the day. Fewer than 2% reported that they stop breathing when sleeping, and this was found more frequently among habitual snorers (7%, P < .001) and those sleepy during the day (5%. P < .001). The prevalence of habitual snoring declined in the older age groups, was higher among those with greater Body Mass Index scores, and was not associated with the reporting of daytime sleepiness, diagnosis of heart disease, stroke, dementia, or cognitive impairment. Daytime sleepiness was more prevalent at older ages and was associated with a higher prevalence of heart disease and with cognitive impairment and dementia, chronic obstructive pulmonary disease, and diabetes. Self-reported apnea was associated only with a history of pneumonia. Three-year mortality was not associated with these symptoms after adjusting for prevalent heart disease and cognitive impairment. CONCLUSION: Symptoms of sleep apnea are reported less frequently in older Japanese-American men. Excessive daytime sleepiness is associated with poor cognition and dementia, but whether it also is an indicator for sleep apnea in this age group remains unclear. Epidemiologic studies of sleep apnea in older adults will require polysomnography to determine accurately the correlates and consequences of this condition. C1 NIA, Bethesda, MD 20892 USA. Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. Univ Arizona, Coll Med, Resp Sci Ctr, Tucson, AZ USA. RP Foley, DJ (reprint author), NIA, Rm 3C-309,Bethesda Gateway Bldg,7201 Wisconsin Av, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [N01-HC-02901]; NIA NIH HHS [N01-AG-4-2149] NR 36 TC 55 Z9 60 U1 3 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 1999 VL 47 IS 5 BP 524 EP 528 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 194NU UT WOS:000080201100004 PM 10323643 ER PT J AU Lakatta, EG AF Lakatta, EG TI Cardiovascular aging research: The next horizons SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID SMOOTH-MUSCLE CELLS; AGE-ASSOCIATED CHANGES; GROWTH-FACTOR-BETA; SARCOPLASMIC-RETICULUM CA-2+-ATPASE; ELASTIN-BINDING-PROTEIN; RAT CARDIAC MYOCYTES; EXTRACELLULAR-MATRIX; MESSENGER-RNA; YOUNG-ADULT; FIBRONECTIN EXPRESSION C1 NIA, Intramural Res Program, Ctr Gerontol Res, Cardiovasc Sci Lab,NIH, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), NIA, Intramural Res Program, Ctr Gerontol Res, Cardiovasc Sci Lab,NIH, 600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 92 TC 79 Z9 83 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 1999 VL 47 IS 5 BP 613 EP 625 PG 13 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 194NU UT WOS:000080201100019 PM 10323658 ER PT J AU Wright, LW Naudini, HKG Aronson, AR Rindflesch, TC AF Wright, LW Naudini, HKG Aronson, AR Rindflesch, TC TI Hierarchical concept indexing of full-text documents in the Unified Medical Language System (R) Information Sources Map SO JOURNAL OF THE AMERICAN SOCIETY FOR INFORMATION SCIENCE LA English DT Article ID RETRIEVAL; PROJECT AB Full-text documents are a vital and rapidly growing part of online biomedical information. A single Barge document can contain as much information as a small database, but normally lacks the tight structure and consistent indexing of a database. Retrieval systems will often miss highly relevant parts of a document if the document as a whole appears irrelevant. Access to full-text information is further complicated by the need to search separately many disparate information resources. This research explores how these problems can be addressed by the combined use of two techniques: 1) natural language processing for automatic concept-based indexing of full text, and 2) methods for exploiting the structure and hierarchy of full-text documents. We describe methods for applying these techniques to a large collection of full-text documents drawn from the Health Services/Technology Assessment Text (HSTAT) database at the National Library of Medicine (NLM), and examine how this hierarchical concept indexing can assist: both document- and source-level retrieval in the context of NLM's Information Sources Map project. C1 Natl Lib Med, Bethesda, MD 20894 USA. Johns Hopkins Univ, SAIS Bologna Ctr, I-40126 Bologna, Italy. RP Wright, LW (reprint author), NCI, Int Canc Informat Ctr, 9030 Old Georgetown Rd, Bethesda, MD 20892 USA. OI Grossetta Nardini, Holly/0000-0001-5563-6848 NR 37 TC 6 Z9 6 U1 1 U2 1 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 MAY 1 PY 1999 VL 50 IS 6 BP 514 EP 523 PG 10 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA 189BL UT WOS:000079884200006 ER PT J AU Kim, GH Ecelbarger, C Knepper, MA Packer, RK AF Kim, GH Ecelbarger, C Knepper, MA Packer, RK TI Regulation of thick ascending limb ion transporter abundance in response to altered acid/base intake SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC METABOLIC-ACIDOSIS; MESSENGER-RNA; AMMONIUM TRANSPORT; MOLECULAR-CLONING; ATPASE ACTIVITY; HENLES LOOP; RAT; KIDNEY; EXPRESSION; MECHANISMS AB Changes in ammonium excretion with acid/base perturbations are dependent on changes in medullary ammonium accumulation mediated by active NH4+ absorption by the medullary thick ascending limb. To investigate whether alterations in the abundance of medullary thick ascending limb ion transporters, namely the apical Na+/K+ (NH4+)/2Cl(-)-cotransporter (BSC-1), the apical Na+/H+-exchanger (NHE3), and the Na+/K+-ATPase alpha 1-subunit, may be responsible in part for altered medullary ammonium accumulation, semiquantitative immunoblotting studies were performed using homogenates from the inner stripe of the rat renal outer medulla. After 7 d of NH4Cl (7.2 mmol/220 g body wt per d) loading (associated with increased medullary ammonium accumulation), neither BSC-1 nor Na+/K+-ATPase protein expression was altered, but NHE3 protein abundance was significantly increased. On the other hand, both BSC-1 and Na+/K+-ATPase protein abundance was increased significantly in rats fed NaHCO3 (7.2 mmol/220 g body wt per d) for 7 d. Rats fed a high-NaCl diet (7.7 mEq Na+/220 g body wt per d) for 5 d also showed marked increases in both BSC-1 and Na+/K+-ATPase expression. The expression level of NHE3 protein did not change with either NaHCO3 or high NaCl intake. None of these three transporters showed a significant difference in abundance between the groups fed equimolar (7.2 mmol/220 g body wt per d for 7 d) NaHCO3 or NaCl. It is concluded that outer medullary BSC-1 and Na+/K+-ATPase alpha 1-subunit protein abundance is increased by chronic Na+ loading but not by acid/base perturbations and that outer medullary NHE3 protein abundance is increased by chronic NH4Cl loading. C1 NHLBI, NIH, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. George Washington Univ, Dept Biol Sci, Washington, DC 20052 USA. RP Knepper, MA (reprint author), NHLBI, NIH, Kidney & Electrolyte Metab Lab, Bldg 10,Room 6N260,10 Ctr Dr MSC 1603, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 HL999999, Z01 HL001285-21]; NHLBI NIH HHS [ZO1-HL01282-09] NR 34 TC 78 Z9 79 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAY PY 1999 VL 10 IS 5 BP 935 EP 942 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 189TV UT WOS:000079923000003 PM 10232678 ER PT J AU Wood, BJ Khan, MA McGovern, F Harisinghani, M Hahn, PF Mueller, PR AF Wood, BJ Khan, MA McGovern, F Harisinghani, M Hahn, PF Mueller, PR TI Imaging guided biopsy of renal masses: Indications, accuracy and impact on clinical management SO JOURNAL OF UROLOGY LA English DT Article DE kidney; carcinoma, renal cell; biopsy; ultrasonography; computerized tomography ID CELL CARCINOMA; DIAGNOSIS; TUMOR AB Purpose: We evaluated the indications, accuracy and impact of image guided biopsy of focal renal masses, Materials and Methods: We retrospectively reviewed 79 image guided renal biopsies in 73 patients. indications, imaging, and histological and clinical features were analyzed. We assumed that nephrectomy, partial nephrectomy or surgical biopsy of suspicious masses would be done when no percutaneous biopsy had been performed. A change in management was defined as surgical to nonsurgical. Results: Clinical management was altered due to results in 32 of the 79 biopsies (41%) in cases managed nonoperatively, including positive and negative biopsies in those followed clinically and with imaging. Of 79 biopsies 49 (62%) were diagnosed positive for malignancy, including 15 (31%) that were not and 34 (69%) that were renal cell carcinoma. The histological diagnosis was negative on 25 biopsies (32%) and positive or negative on 74 (94%). All 5 of the 79 false-negative biopsies (6%) were due to insufficient tissue and involved highly suspicious imaging findings that required further evaluation, such as repeat biopsy or surgery. Renal cell carcinoma was identified in 4 of the 5 cases. In 12 of the 24 patients (50%) with a pre-biopsy history of nonrenal cancer biopsies were diagnostic of nonrenal cancer. No patient had major complications and in 4 small hematomas were treated with observation only. Conclusions: Image guided renal mass biopsy is safe, reliable and accurate, and it changes clinical management; in many cases by avoiding nephrectomy or other surgical options. Radiologists should promote imaging guided biopsy as a potentially useful option for managing suspicious or indeterminate renal masses. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NIH, Dept Radiol, Bethesda, MD 20892 USA. RP Wood, BJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 12 TC 133 Z9 135 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 1999 VL 161 IS 5 BP 1470 EP 1474 DI 10.1016/S0022-5347(05)68929-X PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 185JY UT WOS:000079666900013 PM 10210375 ER PT J AU Walther, MM Choyke, PL Glenn, G Lyne, JC Rayford, W Venzon, D Linehan, WM AF Walther, MM Choyke, PL Glenn, G Lyne, JC Rayford, W Venzon, D Linehan, WM TI Renal cancer in families with hereditary renal cancer: Prospective analysis of a tumor size threshold for renal parenchymal sparing surgery SO JOURNAL OF UROLOGY LA English DT Article DE kidney; carcinoma, renal cell; Hippel-Lindau disease; neoplasm metastases ID VONHIPPEL-LINDAU-DISEASE; TERM FOLLOW-UP; CELL CARCINOMA; SUPPRESSOR GENE; LESIONS; MANAGEMENT; ENUCLEATION; PATHOLOGY; STAGE; CT AB Purpose: Patients with hereditary fc,rms of renal cancer are at risk for new tumors and metastases. Renal parenchymal sparing surgery has been performed to preserve renal function and quality of life, and prevent metastases. We evaluated a 3 cm. threshold for performing renal parenchymal sparing surgery in patients with von Hippel-Lindau disease and hereditary papillary renal cancer. Materials and Methods: Patients with von Hippel-Lindau disease or hereditary papillary renal cancer and renal cancer were identified by screening affected kindred and by kindred history. Patients with small tumors were followed with serial imaging studies until the largest renal tumor was 3 cm., when renal parenchymal sparing surgery was performed. Renal tumors greater than 3 cm. were resected without delay. Parenchymal sparing techniques were used when possible in each group. Results: The 3 cm. surgical threshold was Evaluated in 52 patients with von Hippel-Lindau disease (group 1) at a median followup of 60 months (range 6 to 205). None of these patients had metastatic disease and none has required renal transplantation or dialysis. In 44 patients with von Hippel-Lindau disease (group 2) renal tumors larger than 3 cm. developed. Median followup from the initial radiological diagnosis of renal cancer in this group was 66.5 months (range 0 to 321). Patients in group 1 underwent parenchymal sparing surgery instead of nephrectomy more frequently than those in group 2 (46 of 48 operations or 96% versus 45 of 72 or 63%, Fisher's exact test p <0.0001). In contrast to patients in group 1, metastatic renal cancer developed in 11 of the 44 in group 2 (25%) (Fisher's exact test p <0.0001). A total of 23 patients with hereditary papillary renal cancer were also identified. Median followup in these cases was 44 months (range 0 to 237). Ten patients had tumors less than 3 cm. No patient with tumors less than 3 cm. and 2 of the 13 (15%) with larger tumors had metastases. Conclusions: Using a 3 cm. renal tumor diameter as an indication for renal surgery no patient with renal cancer and von Hippel-Lindau disease or hereditary papillary renal cancer had metastatic disease regardless of the number of tumors. Using a lesion size of 3 cm. as a threshold for performing renal parenchymal sparing surgery may help to prevent metastatic disease, unnecessary renal damage due to frequent surgery and renal dialysis or transplantation. C1 NCI, Urol Oncol Branch, Dept Radiol, Genet Epidemiol Branch,NCI, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. RP Walther, MM (reprint author), NCI, Urol Oncol Branch, Dept Radiol, Genet Epidemiol Branch,NCI, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 35 TC 117 Z9 123 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 1999 VL 161 IS 5 BP 1475 EP 1479 DI 10.1016/S0022-5347(05)68930-6 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 185JY UT WOS:000079666900014 PM 10210376 ER PT J AU Betakova, T Wolffe, EJ Moss, B AF Betakova, T Wolffe, EJ Moss, B TI Regulation of vaccinia virus morphogenesis: Phosphorylation of the A14L and A17L membrane proteins and C-terminal truncation of the A17L protein are dependent on the F10L kinase SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIN-CONTAINING MICROVILLI; TEMPERATURE-SENSITIVE MUTANTS; TO-CELL SPREAD; ENVELOPE PROTEIN; INTERMEDIATE COMPARTMENT; PROTEOLYTIC MATURATION; CORE PROTEINS; ENDOPLASMIC-RETICULUM; VIRION MORPHOGENESIS; STRUCTURAL PROTEINS AB This study focused on three vaccinia virus-encoded proteins that participate in early steps of virion morphogenesis: the A17L and A14L membrane proteins and the F10L protein kinase, We found that (i) the A17L protein was cleaved at or near an AGX consensus motif at amino acid 185, thereby removing its acidic C terminus; (ii) the nontruncated form was associated with immature virions, but only the C-terminal truncated protein was present in mature virions; (iii) the nontruncated form of the A17L protein was phosphorylated on serine, threonine, and tyrosine residues, whereas the truncated form was unphosphorylated; (iv) nontruncated and truncated forms of the A17L protein existed in a complete with the A14L membrane protein; (v) C-terminal cleavage of the A17L protein and phosphorylation of the A17L and A14L proteins failed to occur in cells infected with a F10L kinase mutant at the nonpermissive temperature; and (vi) the F10L kinase was the only viral late protein that was necessary for phosphorylation of the A17L protein, whereas additional proteins were needed for C-terminal cleavage. We suggest that phosphorylation of the A17L and A14L proteins is mediated by the F10L kinase and is required to form the membranes associated with immature virions. Removal of phosphates and the A17L acidic C-terminal peptide occur during the transition to mature virions. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 4,Room 229,4 Ctr Dr,MSC 0445, Bethesda, MD 20892 USA. NR 57 TC 58 Z9 62 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 MAY PY 1999 VL 73 IS 5 BP 3534 EP 3543 PG 10 WC Virology SC Virology GA 185ZG UT WOS:000079701100004 PM 10196242 ER PT J AU Valk, PJM Vankan, Y Joosten, M Jenkins, NA Copeland, NG Lowenberg, B Delwel, R AF Valk, PJM Vankan, Y Joosten, M Jenkins, NA Copeland, NG Lowenberg, B Delwel, R TI Retroviral insertions in Evi12, a novel common virus integration site upstream of Tra1/Grp94, frequently coincide with insertions in the gene encoding the peripheral cannabinoid receptor Cnr2 SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; REGULATED PROTEIN GRP94; REJECTION ANTIGEN GP96; T-CELL LYMPHOMAS; ENDOPLASMIC-RETICULUM; MYELOID-LEUKEMIA; PORCINE BRAIN; EXPRESSION; ACTIVATION; MICE AB The common virus integration site (VIS) Evi11 was recently identified within the gene encoding the hematopoietic G-protein-coupled peripheral cannabinoid receptor Cnr2 (also referred to as Cb2). Here we show that Cnr2 is a frequent target (12%) for insertion of Cas-Br-M murine leukemia virus (MuLV) in primary tumors in NIH/Swiss mice. Multiple provirus insertions in Evi11 were cloned and shown to be located within the 3' untranslated region of the candidate proto oncogene Cnr2. These results suggest that proviral insertion in the Cnr2 gene is an important step in Cas-Br-M MuLV-induced leukemogenesis in NIH/Swiss mice. To isolate Evi11/Cnr2 collaborating proto-oncogenes, we searched for novel common VISs in the Cas-Br-M MuLV-induced primary tumors and identified a novel frequent common VIS, Evi12 (14%). Interestingly, 54% of the Evi11/Cnr2-rearranged primary tumors contained insertions in Evi12 as well, which suggests cooperative action of the target genes in these two common VISs in leukemogenesis. By interspecific backcross analysis it was shown that Evi12 resides on mouse chromosome 10 in a region that shares homology with human chromosomes 12q and 19p, Sequence analysis demonstrated that Evi12 is located upstream of the gene encoding the molecular chaperone Tra1/Grp94, which was previously mapped to mouse chromosome 10 and human chromosome 12q22-24. Thus, Tra1/Grp94 is a candidate target gene for retroviral activation or inactivation in Evi12. However, Northern and Western blot analyses did not provide evidence that proviral insertion had altered the expression of Tra1/Grp94. Additional studies are required to determine whether Tra1/Grp94 or another candidate proto-oncogene in Evi12 is involved in leukemogenesis. C1 Erasmus Univ, Inst Hematol, NL-3000 DR Rotterdam, Netherlands. NCI, Mammalian Genet Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. RP Delwel, R (reprint author), Erasmus Univ, Inst Hematol, POB 1738, NL-3000 DR Rotterdam, Netherlands. NR 58 TC 18 Z9 19 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 MAY PY 1999 VL 73 IS 5 BP 3595 EP 3602 PG 8 WC Virology SC Virology GA 185ZG UT WOS:000079701100012 PM 10196250 ER PT J AU Lyu, MS Nihrane, A Kozak, CA AF Lyu, MS Nihrane, A Kozak, CA TI Receptor-mediated interference mechanism responsible for resistance to polytropic leukemia viruses in Mus castaneus SO JOURNAL OF VIROLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; HOST-REACTION; MOUSE CELLS; WILD MICE; MURINE; MCF; INFECTION; GENE; SUSCEPTIBILITY; RETROVIRUSES AB The Asian mouse Mus castaneus is resistant to infection by the polytropic mink cell focus-inducing (MCF) subgroup of murine leukemia viruses (MuLVs). Genetic crosses showed this recessive resistance to be governed by a single gene that maps at or near the gene encoding the polytropic viral receptor, Rmc1, To investigate this resistance, we mated M, castaneus with mice carrying the wild mouse Sxv variant of the Rmc1 receptor that allows infection by xenotropic as well as polytropic virus. Unlike other F-1 hybrids of M, castaneus, these F-1 mice were resistant to both xenotropic and polytropic classes of MuLVs, Analysis of backcrossed progeny of the F-1 hybrids mated to Sxv mice indicates that resistance is due to inheritance of two M. castaneus genes, Cells from individual backcross mice were also examined for cell surface antigen by fluorescence-activated cell sorter analysis with monoclonal antibodies reactive with xenotropic or MCF virus env glycoproteins. A correlation was observed between virus resistance and antigen, suggesting that virus resistance is due to expression of endogenous viral envelope genes that interfere with infection by exogenous virus. Since the inbred strain Rmc1 receptor remains functional in the presence of these M, castaneus genes, and since M, castaneus contains multiple copies of xenotropic MuLV env genes, we suggest that these resistance genes control expression of xenotropic env glycoprotein that interferes with exogenous virus in cells containing the Sn, variant of Rmc1. C1 NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. RP Kozak, CA (reprint author), NIAID, Mol Microbiol Lab, Bldg 4,Room 329,4 Ctr Dr MSC 0460, Bethesda, MD 20892 USA. NR 24 TC 18 Z9 18 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 MAY PY 1999 VL 73 IS 5 BP 3733 EP 3736 PG 4 WC Virology SC Virology GA 185ZG UT WOS:000079701100028 PM 10196266 ER PT J AU Dittmer, U Brooks, DM Hasenkrug, KJ AF Dittmer, U Brooks, DM Hasenkrug, KJ TI Protection against establishment of retroviral persistence by vaccination with a live attenuated virus SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; CD4(+) T-CELLS; MONOCLONAL-ANTIBODIES; ENVELOPE PROTEIN; FRIEND-LEUKEMIA; INFECTION; DISEASE; GENE; ERYTHROLEUKEMIA AB Many human viruses not only cause acute diseases but also establish persistent infections. Such persistent viruses can cause chronic diseases or can reactivate to cause acute diseases in AIDS patients or patients receiving immunosuppressive therapies. While the prevention of persistent infections is an important consideration in the design of modern vaccines, surprisingly little is known about this aspect of protection. In the current study, we tested the feasibility of vaccine prevention of retroviral persistence by using a Friend virus model that we recently developed. In this model, persistent virus can be detected at very low levels by immunosuppressing the host to reactivate virus or by transferring persistently infected spleen cells into highly susceptible mice, Two vaccines were analyzed, a recombinant vaccinia virus vector expressing Friend virus envelope protein and a live attenuated Friend virus. Both vaccines reduced pathogenic virus loads to levels undetectable by infectious center assays, However, only the live, attenuated vaccine prevented immunosuppression-induced reactivation of persistent virus. Thus, even very low levels of persistent Friend virus posed a significant threat during immunosuppression, Our results demonstrate that vaccine protection against establishment of retroviral persistence is attainable. C1 NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Hasenkrug, KJ (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM khasenkrug@nih.gov NR 32 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 MAY PY 1999 VL 73 IS 5 BP 3753 EP 3757 PG 5 WC Virology SC Virology GA 185ZG UT WOS:000079701100031 PM 10196269 ER PT J AU Fox, JM Bloom, ME AF Fox, JM Bloom, ME TI Identification of a cell surface protein from Crandell feline kidney cells that specifically binds Aleutian mink disease parvovirus SO JOURNAL OF VIROLOGY LA English DT Article ID BACULOVIRUS VECTOR SYSTEM; CANINE PARVOVIRUS; PUTATIVE RECEPTOR; VIRUS RECEPTORS; B19 PARVOVIRUS; EMPTY CAPSIDS; ADULT MINK; INFECTION; EXPRESSION; REPLICATION AB Aleutian mink disease parvovirus (ADV) is the etiological agent of Aleutian disease of mink. The acute disease caused by ADV consists of permissive infection of alveolar type II cells that results in interstitial pneumonitis. The permissive infection is experimentally modeled in vitro by infecting Crandell feline kidney (CrFK) cells,vith a tissue culture-adapted isolate of ADV, ADV-G, ADV-G VP2 empty virions expressed in a recombinant baculovirus system were analyzed for the ability to bind to the surface of CrFK cells. Radiolabeled VP2 virions bound CrFK cells specifically, while they did not bind either Mus dunni or Spodoptera frugiperda cells, cells which are resistant to ADV infection. The binding to CrFK cells was competitively inhibited by VP2 virions but not by virions of cowpea chlorotic mottle virus (CCMV), another unenveloped virus similar in size to ADV, Furthermore, preincubation of CrFK cells with the VP2 virions blocked infection by ADV-G. The VP2 virions were used in a virus overlay protein binding assay to identify a single protein of approximately 67 kDa, named ABP (for ADV binding protein), that demonstrates specific binding of VP2 virions. Exogenously added VP2 virions were able to competitively inhibit the binding of labeled VP2 virions to ABP, while CCMV virions had no effect. Polyclonal antibodies raised against ABP reacted with ABP on the outer surface of CrFK cells and blocked infection of CrFK cells by ADV-G, In addition, VP2 virion attachment to CrFK cells was blocked when the VP2 virions were preincubated with partially purified ABP, Taken together, these results indicate that ABP is a cellular receptor for ADV. C1 NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Fox, JM (reprint author), 903 S 4th St, Hamilton, MT 59840 USA. EM jfox@atlas.niaid.nih.gov NR 51 TC 14 Z9 15 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 MAY PY 1999 VL 73 IS 5 BP 3835 EP 3842 PG 8 WC Virology SC Virology GA 185ZG UT WOS:000079701100040 PM 10196278 ER PT J AU Glushakova, S Grivel, JC Suryanarayana, K Meylan, P Lifson, JD Desrosiers, R Margolis, L AF Glushakova, S Grivel, JC Suryanarayana, K Meylan, P Lifson, JD Desrosiers, R Margolis, L TI Nef enhances human immunodeficiency virus replication and responsiveness to interleukin-2 in human lymphoid tissue ex vivo SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL ACTIVATION; TYPE-1 NEF; PRIMARY LYMPHOCYTES; HIV-1 INFECTION; IN-VITRO; GENE; PATHOGENICITY; HISTOCULTURES; TRANSCRIPTION; RETROVIRUS AB The nef gene is important for the pathogenicity associated with simian immunodeficiency virus infection in rhesus monkeys and with human immunodeficiency virus type 1 (HIV-1) infection in humans. The mechanisms by which nef contributes to pathogenesis in vivo remain unclear,We investigated the contribution of nef to HIV-1 replication in human lymphoid tissue ex vivo by studying infection with parental HIV-I strain NL4-3 and with a nef mutant (Delta nefNL4-3). In human tonsillar histocultures, NL4-3 replicated to higher levels than Delta nefNL4-3 did. Increased, virus production with NL4-3 infection was associated with increased numbers of productively infected cells and greater loss of CD4(+) T cells over time, While the numbers of productively infected T cells were increased in the presence of nef, the levels of viral expression and production per infected T cell were similar whether the nef gene was present or not, Exogenous interleukin-2 (IL-2) increased HIV-1 production in NL4-3-infected tissue in a dose-dependent manner. In contrast, Delta nefNL4-3 production was enhanced only marginally by IL-2, Thus, Nef can facilitate HIV-1 replication in human lymphoid tissue ex vivo by increasing the numbers of productively infected cells and by increasing the responsiveness to IL-2 stimulation. C1 NICHHD, Lab Mol & Cellular Biophys, NIH, Bethesda, MD 20892 USA. SAIC Frederick, AIDS Vaccine Program, Lab Retroviral Pathogenesis, Frederick, MD 21702 USA. CHU Vaudois, Inst Microbiol, CH-1011 Lausanne, Switzerland. New England Reg Primate Res Ctr, Southborough, MA 01772 USA. RP Desrosiers, R (reprint author), NICHHD, Lab Mol & Cellular Biophys, NIH, Bldg 10,Rm 10D14, Bethesda, MD 20892 USA. NR 34 TC 62 Z9 63 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 MAY PY 1999 VL 73 IS 5 BP 3968 EP 3974 PG 7 WC Virology SC Virology GA 185ZG UT WOS:000079701100054 PM 10196292 ER PT J AU Mascola, JR Lewis, MG Stiegler, G Harris, D VanCott, TC Hayes, D Louder, MK Brown, CR Sapan, CV Frankel, SS Lu, YC Robb, ML Katinger, H Birx, DL AF Mascola, JR Lewis, MG Stiegler, G Harris, D VanCott, TC Hayes, D Louder, MK Brown, CR Sapan, CV Frankel, SS Lu, YC Robb, ML Katinger, H Birx, DL TI Protection of macaques against pathogenic simian/human immunodeficiency virus 89.6PD by passive transfer of neutralizing antibodies SO JOURNAL OF VIROLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; RHESUS MACAQUES; HIV IMMUNOGLOBULIN; IMMUNE GLOBULIN; INFECTIOUS-DISEASES; CYNOMOLGUS MONKEYS; PRIMARY ISOLATE; CHIMERIC HUMAN; SIV INFECTION; TYPE-1 AB The role of antibody in protection against human immunodeficiency virus (HIV-1) has been difficult to study in animal models because most primary HIV-1 strains do not infect nonhuman primates. Using a chimeric simian/human immunodeficiency virus (SHIV) based on the envelope of a primary isolate (HIV-89.6), we performed passive-transfer experiments in rhesus macaques to study the role of anti-envelope antibodies in protection. Based on prior in vitro data showing neutralization synergy by antibody combinations, we evaluated HIV immune globulin (HIVIG), and human monoclonal antibodies (MAbs) 2F5 and 2G12 given alone, compared with the double combination 2F5/2G12 and the triple combination HIVIG/2F5/2G12. Antibodies were administered 24 h prior to intravenous challenge with the pathogenic SHIV-89.6PD. Six control monkeys displayed high plasma viremia, rapid CD4(+)-cell decline, and clinical AIDS within 14 weeks. Of six animals given HIVIG/2F5/2G12, three were completely protected; the remaining three animals became SHIV infected but displayed reduced plasma viremia and near normal CD4(+)-cell counts. One of three monkeys given 2F5/2G12 exhibited only transient evidence of infection; the other two had marked reductions in viral load. All monkeys that received HMG, 2F5, or 2G12 alone became infected and developed high-level plasma viremia. However, compared to controls, monkeys that received HIVIG or MAb 2G12 displayed a less profound drop in CD4(+) T cells and a more benign clinical course. These data indicate a general correlation between in vitro neutralization and protection and suggest that a vaccine that elicits neutralizing antibody should have a protective effect against HIV-1 infection or disease. C1 Walter Reed Army Inst Res, Div Retrovirol, Rockville, MD 20850 USA. Henry M Jackson Fdn, Rockville, MD 20850 USA. Agr Univ Vienna, Inst Appl Microbiol, A-1180 Vienna, Austria. NIAID, NIH, Rockville, MD 20852 USA. NABI, Boca Raton, FL 33487 USA. AVANT Immunotherapeut, Needham, MA 02494 USA. RP Mascola, JR (reprint author), Walter Reed Army Inst Res, Div Retrovirol, 1 Taft Court,Suite 250, Rockville, MD 20850 USA. FU NHLBI NIH HHS [HL59718] NR 56 TC 597 Z9 604 U1 0 U2 12 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 MAY PY 1999 VL 73 IS 5 BP 4009 EP 4018 PG 10 WC Virology SC Virology GA 185ZG UT WOS:000079701100059 PM 10196297 ER PT J AU Asada, H Klaus-Kovtun, V Golding, H Katz, SI Blauvelt, A AF Asada, H Klaus-Kovtun, V Golding, H Katz, SI Blauvelt, A TI Human herpesvirus 6 infects dendritic cells and suppresses human immunodeficiency virus type 1 replication in coinfected cultures SO JOURNAL OF VIROLOGY LA English DT Article ID CD4+ T-CELLS; HIV-1 INFECTION; MASSIVE LYMPHADENOPATHY; PRODUCTIVE INFECTION; SINUS HISTIOCYTOSIS; LANGERHANS CELLS; HHV-6 INFECTION; LYMPHOCYTES-T; BLOOD; AIDS AB Human herpesvirus 6 (HHV-6) has been implicated as a cofactor in the progressive loss of CD4(+) T cells observed in AIDS patients. Because dendritic cells (DC) play an important role in the immunopathogenesis of human immunodeficiency virus (HIV) disease, we studied the infection of DC by HHV-6 and coinfection of DC by HHV-6 and HIV. Purified immature DC (derived from adherent peripheral blood mononuclear cells in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4) could be infected with HHV-6, as determined by PCR analyses, intracellular monoclonal antibody staining, and presence of virus in culture supernatants. However, HHV-6-infected DC demonstrated neither cytopathic changes nor functional defects. Interestingly, HHV-6 markedly suppressed HIV replication and syncytium formation in coinfected DC cultures. This HHV-6-mediated anti-HIV effect was DC specific, occurred when HHV-6 was added either before or after HIV, and was not due to decreased surface expression or function of CD4, CXCR4, or CCR5. Conversely, HIV had no demonstrable effect on HHV-6 replication, These findings suggest that HHV-6 may protect DC from HIV-induced cytopathicity in AIDS patients. We also demonstrate that interactions between HIV and herpesviruses are complex and that the observable outcome of dual infection is dependent on the target cell type. C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. RP Blauvelt, A (reprint author), NCI, Dermatol Branch, Bldg 10,Room 12N238,10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA. EM Andrew_Blauvelt@nih.gov NR 68 TC 38 Z9 40 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 MAY PY 1999 VL 73 IS 5 BP 4019 EP 4028 PG 10 WC Virology SC Virology GA 185ZG UT WOS:000079701100060 PM 10196298 ER PT J AU Ono, A Freed, EO AF Ono, A Freed, EO TI Binding of human immunodeficiency virus type 1 Gag to membrane: Role of the matrix amino terminus SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; PARTICLE FORMATION; PLASMA-MEMBRANE; ENVELOPE GLYCOPROTEIN; ENDOPLASMIC-RETICULUM; LIFE-CYCLE; N-TERMINUS; PROTEIN; DOMAIN; ASSOCIATION AB Binding of the human immunodeficiency virus type 1 (HIV-1) Gag protein precursor, Pr55(Gag), to membrane is an indispensable step in virus assembly. Previously, we reported that a matrix (MA) residue 6 substitution (6VR) imposed a virus assembly defect similar to that observed with myristylation-defective mutants, suggesting that the 6VR change impaired membrane binding. Intriguingly, the 6VR mutation had no effect on Gag myristylation, The defective phenotype imposed by 6VR was reversed by changes at other positions in MA, including residue 97, In this study, we use several biochemical methods to demonstrate that the residue 6 mutation, as well as additional substitutions in MA amino acids 7 and 8, reduce membrane binding without affecting N-terminal myristylation. This effect is observed in the context of Pr55(Gag), a truncated Gag containing only MA and CA, and in MA itself. The membrane binding defect imposed by the 6VR mutation is reversed by second-site changes in MA residues 20 and 97, both of which, when present alone, increase membrane binding to levels greater than those for the wild type. Both reduced and enhanced membrane binding imposed by the MA substitutions depend upon the presence of the N-terminal myristate. The results support the myristyl switch model recently proposed for the regulation of Gag membrane binding, according to which membrane binding is determined by the degree of exposure or sequestration of the N-terminal myristate moiety. Alternatively, insertion of the myristate into the lipid bilayer might be a prerequisite event for the function of other distinct MA-encoded membrane binding domains. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Ono, A (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Rm 307, Bethesda, MD 20892 USA. NR 55 TC 182 Z9 185 U1 0 U2 4 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 MAY PY 1999 VL 73 IS 5 BP 4136 EP 4144 PG 9 WC Virology SC Virology GA 185ZG UT WOS:000079701100072 PM 10196310 ER PT J AU Zong, JC Ciufo, DM Alcendor, DJ Wan, XY Nicholas, J Browning, PJ Rady, PL Tyring, SK Orenstein, JM Rabkin, CS Su, IJ Powell, KF Croxson, M Foreman, KE Nickoloff, BJ Alkan, S Hayward, GS AF Zong, JC Ciufo, DM Alcendor, DJ Wan, XY Nicholas, J Browning, PJ Rady, PL Tyring, SK Orenstein, JM Rabkin, CS Su, IJ Powell, KF Croxson, M Foreman, KE Nickoloff, BJ Alkan, S Hayward, GS TI High-level variability in the ORF-K1 membrane protein gene at the left end of the Kaposi's sarcoma-associated herpesvirus genome defines four major virus subtypes and multiple variants or clades in different human populations SO JOURNAL OF VIROLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; LYMPHOMA CELL-LINES; DNA-SEQUENCES; PERIPHERAL-BLOOD; UNITED-STATES; ENVELOPE GLYCOPROTEIN; TRANSFORMING PROTEIN; SIGNAL-TRANSDUCTION; STRAIN VARIABILITY; AIDS PATIENTS AB Infection with Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) or human herpes virus 8 (HHV8) is common in certain parts of Africa, the Middle East, and the Mediterranean, but is rare elsewhere, except in AIDS patients. Nevertheless, HHV8 DNA is found consistently in nearly all classical, endemic, transplant and AIDS-associated KS lesions as well as in some rare AIDS-associated lymphomas, The concept that HHV8 genomes fall into several distinct subgroups has been confirmed and refined by PCR DNA sequence analysis of the ORF-K1 gene encoding a highly variable glycoprotein related to the immunoglobulin receptor family that maps at the extreme left-hand end of the HHV-8 genome. Among more than 60 different tumor samples from the United States, central Africa, Saudi Arabia, Taiwan, and New Zealand, amino acid substitutions were found at a total of 62% of the 289 amino acid positions. These variations defined four major subtypes and 13 distinct variants or clades similar to those found for the HIV ENV protein. The B and D subtype ORF-K1 proteins differ from the A and C subtypes by 30 and 24%, respectively, whereas A and C differ from each other by 15%. In all cases tested, multiple samples from the same patient were identical. Examples of the B subtype were found almost exclusively in KS patients from Africa or of African heritage, whereas the rare B subtypes were found only in KS patients of Pacific Island heritage. In contrast, C subtypes were found predominantly in classic KS and in iatrogenic and AIDS KS in the Middle East and Asia, whereas U.S. AIDS KS samples were primarily A1, A4, and C3 variants. We conclude that this unusually high diversity, in which 85% of the nucleotide changes lead to amino acid changes, reflects some unknown powerful biological selection process that has been acting preferentially on this early lytic cycle membrane signalling protein. Two distinct levels of ORF-K1 variability are recognizable. Subtype-specific variability indicative of long-term evolutionary divergence is both spread throughout the protein as well as concentrated within two IO-amino-acid extracellular domain variable regions (VR1 and VR2), whereas intratypic variability localizes predominantly within a single 25-amino-acid hypervariable Cys bridge loop and apparently represents much more recent changes that have occurred even within specific clades, In contrast, numerous extracellular domain glycosylation sites and Cys bridge residues as well as the ITAM motif in the cytoplasmic domain are fully conserved. Overall, we suggest that rather than being a newly acquired human pathogen, HHV8 is an ancient human virus that is preferentially transmitted in a familial fashion and is difficult to transmit horizontally in the absence of immunosuppression, The division into the four major HHV8 subgroups is probably the result of isolation and founder effects associated with the history of migration of modern human populations out of Africa over the past 35,000 to 60,000 Sears. C1 Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21231 USA. Vanderbilt Univ, Nashville, TN 37232 USA. Univ Texas, Med Branch, Dept Pediat, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Microbiol, Galveston, TX 77555 USA. George Washington Univ, Med Ctr, Dept Pathol, Washington, DC 20037 USA. NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. Natl Cheng Kung Univ Hosp, Dept Pathol, Tainan 704, Taiwan. Auckland Hosp, Virus Diagnost Infect Dis Lab, Auckland, New Zealand. Loyola Univ, Med Ctr, Inst Oncol, Maywood, IL 60153 USA. RP Hayward, GS (reprint author), Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, 725 N Wolfe St,WBSB 317, Baltimore, MD 21205 USA. RI Su, Ih-Jen/B-2655-2010 FU NCI NIH HHS [R01 CA073585, R01 CA73585] NR 75 TC 189 Z9 198 U1 0 U2 2 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 MAY PY 1999 VL 73 IS 5 BP 4156 EP 4170 PG 15 WC Virology SC Virology GA 185ZG UT WOS:000079701100074 PM 10196312 ER PT J AU Newcomb, WW Homa, FL Thomsen, DR Trus, BL Cheng, NQ Steven, A Booy, F Brown, JC AF Newcomb, WW Homa, FL Thomsen, DR Trus, BL Cheng, NQ Steven, A Booy, F Brown, JC TI Assembly of the herpes simplex virus procapsid from purified components and identification of small complexes containing the major capsid and scaffolding proteins SO JOURNAL OF VIROLOGY LA English DT Article ID RECOMBINANT BACULOVIRUSES; MOLECULAR COMPOSITION; SUBSTRATE ICP35; CELL-NUCLEUS; AMINO-ACIDS; C-TERMINUS; TYPE-1; COAT; LOCALIZATION; SUBUNITS AB An in vitro system is described for the assembly of herpes simplex virus type 1 (HSV-1) procapsids beginning with three purified components, the major capsid protein (VP5), the triplexes (VP19C plus VP23), and a hybrid scaffolding protein. Each component was purified from insect cells expressing the relevant protein(s) from an appropriate recombinant baculovirus vector. Procapsids formed when the three purified components were mixed and incubated for 1 h at 37 degrees C, Procapsids assembled in this way were found to be similar in morphology and in protein composition to procapsids formed in vitro from cell extracts containing HSV-1 proteins. When scaffolding and tripler proteins were present in excess in the purified system, greater than 80% of the major capsid protein was incorporated into procapsids. Sucrose density gradient ultracentrifugation studies were carried out to examine the oligomeric state of the purified assembly components. These analyses showed that (i) VP5 migrated as a monomer at all of the protein concentrations tested (0.1 to 1 mg/ml), (ii) VP19C and VP23 migrated together as a complex with the same heterotrimeric composition (VP19C(1)-VP23(2)) as virus triplexes, and (iii) the scaffolding protein migrated as a heterogeneous mixture of oligomers (in the range of monomers to similar to 30mers) whose composition was strongly influenced by protein concentration. Similar sucrose gradient analyses performed with mixtures of VP5 and the scaffolding protein demonstrated the presence of complexes of the two having molecular weights in the range of 200,000 to 600,000. The complexes were interpreted to contain one or two VP5 molecules and up to six scaffolding protein molecules. The results suggest that procapsid assembly may proceed by addition of the latter complexes to regions of growing procapsid shell. They indicate further that procapsids can be formed in vitro from virus-encoded proteins only without any requirement for cell proteins. C1 Univ Virginia, Hlth Sci Ctr, Dept Microbiol, Charlottesville, VA 22908 USA. Univ Virginia, Hlth Sci Ctr, Ctr Canc, Charlottesville, VA 22908 USA. Pharmacia & Upjohn Inc, Infect Dis Res, Kalamazoo, MI 49001 USA. NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. NIH, Computat Biosci & Engn Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. NIH, Natl Ctr Res Resources, Biomed Engn & Instrumentat Program, Bethesda, MD 20892 USA. RP Brown, JC (reprint author), Univ Virginia, Hlth Sci Ctr, Dept Microbiol, Box 441, Charlottesville, VA 22908 USA. EM JCB2G@AVERY.MED.VIRGINIA.EDU FU NIAID NIH HHS [R56 AI037549, AI37549, AI41644, R01 AI037549, R01 AI041644, R56 AI041644] NR 43 TC 82 Z9 86 U1 0 U2 2 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 MAY PY 1999 VL 73 IS 5 BP 4239 EP 4250 PG 12 WC Virology SC Virology GA 185ZG UT WOS:000079701100082 PM 10196320 ER PT J AU Feng, YX Campbell, S Harvin, D Ehresmann, B Ehresmann, C Rein, A AF Feng, YX Campbell, S Harvin, D Ehresmann, B Ehresmann, C Rein, A TI The human immunodeficiency virus type 1 Gag polyprotein has nucleic acid chaperone activity: Possible role in dimerization of genomic RNA and placement of tRNA on the primer binding site SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 NUCLEOCAPSID PROTEIN; MURINE LEUKEMIA-VIRUS; HIGH-AFFINITY BINDING; REVERSE TRANSCRIPTION; SECONDARY STRUCTURE; IN-VITRO; DNA-SYNTHESIS; RICH LOOP; POL GENE; INITIATION AB The formation of an infectious retrovirus particle requires several RNA-RNA interaction events. In particular, the genomic RNA molecules form a dimeric structure, and a cellular tRNA molecule is annealed to an 18-base complementary region (the primer binding site, or PBS) on the genomic RNA, where it will serve as primer for reverse transcription. tRNAs normally possess a highly stable secondary and tertiary structure; it seems unlikely that annealing of a tRNA molecule to the PBS, which involves unwinding of this structure, could occur efficiently at physiological temperatures without the assistance of a cofactor, Many prior studies have shown that the viral nucleocapsid (NC) protein can act as a nucleic acid chaperone (i.e., facilitate annealing events between nucleic acids), and the assays used to demonstrate this activity include its ability to catalyze dimerization of transcripts representing retroviral genomes and the annealing of tRNA to the PBS in vitro. However, mature NC is not required for these events in vivo, since protease-deficient viral mutants, in which NC is not cleaved from the parental Gag polyprotein, are known to contain dimeric RNAs with tRNA annealed to the PBS, In the present experiments, we have tested recombinant human immunodeficiency virus type 1 Gag polyprotein for nucleic acid chaperone activity. The protein was positive by all of our assays, including the ability to stimulate dimerization and to anneal tRNA to the PBS in vitro. In quantitative experiments, its activity was approximately equivalent on a molar basis to that of NC. Based on these results, we suggest that the Gag polyprotein (presumably by its NC domain) catalyzes the annealing of tRNA to the PBS during (or before) retrovirus assembly in vivo. C1 NCI, Retroviral Genet Sect, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Inst Biol Mol & Cellulaire, CNRS, Unite Propre Rech 9002, F-67084 Strasbourg, France. RP Rein, A (reprint author), NCI, Retroviral Genet Sect, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, POB B,Bldg 535, Frederick, MD 21702 USA. NR 36 TC 127 Z9 128 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 MAY PY 1999 VL 73 IS 5 BP 4251 EP 4256 PG 6 WC Virology SC Virology GA 185ZG UT WOS:000079701100083 PM 10196321 ER PT J AU Chiorini, JA Afione, S Kotin, RM AF Chiorini, JA Afione, S Kotin, RM TI Adeno-associated virus (AAV) type 5 Rep protein cleaves a unique terminal resolution site compared with other AAV serotypes SO JOURNAL OF VIROLOGY LA English DT Article ID INHIBITS CELLULAR-TRANSFORMATION; ADENOASSOCIATED VIRUS; GENE-PRODUCT; SEQUENCE REQUIREMENTS; BOVINE PAPILLOMAVIRUS; INTEGRATION SITE; DNA-REPLICATION; BINDING-SITES; IN-VITRO; GENOME AB Adeno-associated virus (AAV) replication depends on two viral components for replication: the AAV nonstructural proteins (Rep) in trans, and inverted terminal repeat (ITR) sequences in cis. AAV type 5 (AAV5) is a distinct virus compared to the other cloned AAV serotypes. Whereas the Rep proteins and ITRs of other serotypes are interchangeable and can be used to produce recombinant viral particles of a different serotype, AAV5 Rep proteins cannot cross-complement in the packaging of a genome with an AAV2 ITR. In vitro replication assays indicated that the block occurs at the level of replication instead of at viral assembly. AAV2 and AAV5 Rep binding activities demonstrate similar affinities for either an AAV2 or AAV5 ITR; however, comparison of terminal resolution site (TRS) endonuclease activities showed a difference in specificity for the two DNA sequences. AAV2 Rep78 cleaved only a type 2 ITR DNA sequence, and AAV5 Rep78 cleaved only a type 5 probe efficiently. Mapping of the AAV5 ITR TRS identified a distinct cleavage site (AGTG TGGC) which is absent from the ITRs of other AAV serotypes. Comparison of the TRSs in the AAV2 ITR, the AAV5 ITR, and the AAV chromosome 19 integration locus identified some conserved nucleotides downstream of the cleavage site but little homology upstream. C1 NHLBI, Mol Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Kotin, RM (reprint author), NHLBI, Mol Hematol Branch, NIH, Bldg 10-7D18,10 Ctr Dr MSC 1654, Bethesda, MD 20892 USA. RI kotin, robert/B-8954-2008 NR 40 TC 47 Z9 47 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 MAY PY 1999 VL 73 IS 5 BP 4293 EP 4298 PG 6 WC Virology SC Virology GA 185ZG UT WOS:000079701100089 PM 10196327 ER PT J AU Esser, MT Mori, T Mondor, I Sattentau, QJ Dey, B Berger, EA Boyd, MR Lifson, JD AF Esser, MT Mori, T Mondor, I Sattentau, QJ Dey, B Berger, EA Boyd, MR Lifson, JD TI Cyanovirin-N binds to gp120 to interfere with CD4-dependent human immunodeficiency virus type 1 virion binding, fusion, and infectivity but does not affect the CD4 binding site on gp120 or soluble CD4-induced conformational changes in gp120 SO JOURNAL OF VIROLOGY LA English DT Article ID ENVELOPE GLYCOPROTEIN GP120; RECOMBINANT VACCINIA VIRUS; HUMAN MONOCLONAL-ANTIBODY; HIV-INACTIVATING PROTEIN; T-CELL LINES; NEUTRALIZATION EPITOPES; LINKED OLIGOSACCHARIDE; GLYCOSYLATION SITES; PRIMARY MACROPHAGES; V3 LOOP AB Cyanovirin-N (CV-N), an 11-kDa protein isolated from the cyanobacterium Nostoc ellipsosporum, potently inactivates diverse strains of human immunodeficiency virus type 1 (HIV-1), HIV-2, and simian immunodeficiency virus. While it has been well established that the viral surface envelope glycoprotein gp120 is a molecular target of CV-N, the detailed mechanism of action is of further interest. We compared matched native and CVN-treated virus preparations in a panel of assays that measure viral replication, assessing successive stages of the viral life cycle. CV-N-treated virions failed to infect cells as detected by p24 production and quantitative PCR for HIV-1 reverse transcription products, whereas treatment of the target cells did not block infection, confirming that CV-N acts at the level of the virus, not the target cell, to abort the initial infection process. Compared to native HIV-1 preparations, CV-N-treated HIV-1 virions showed impaired CD4-dependent binding to CD4(+) T cells and did not mediate "fusion from without" of CD4(+) target cells. CV-N also blocked HIV envelope glycoprotein Env-induced, CD4-dependent cell-cell fusion, Mapping studies with monoclonal antibodies (MAbs) to defined epitopes on the HIV-1 envelope glycoprotein indicated that CV-N binds to gp120 in a manner that does not occlude or alter the CD4 binding site or V3 loop or other domains on gp120 recognized by defined MAbs and does not interfere with soluble CD4-induced conformational changes in gp120, Binding of CV-N to soluble gp120 or virions inhibited subsequent binding of the unique neutralizing MAb, 2G12, which recognizes a glycosylation-dependent epitope, However, prior binding of 2G12 MAb to gp120 did not block subsequent binding by CV-N, These results help clarify the mechanism of action of CV-N and suggest that the compound may act in part by preventing essential interactions between the envelope glycoprotein and target cell receptors, This proposed mechanism is consistent with the extensive activity profile of CV-N against numerous isolates of HIV-1 and other lentiviruses and supports the potential broad utility of this protein as a microbicide to prevent the sexual transmission of HIV. C1 NCI, Retroviral Pathogenesis Lab, AIDS Vaccine Program, SAIC Frederick,Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Ctr Immunol Marseille Luminy, Marseille, France. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Lifson, JD (reprint author), NCI, Retroviral Pathogenesis Lab, AIDS Vaccine Program, SAIC Frederick,Frederick Canc Res & Dev Ctr, Bldg 535,5th Floor, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-560000] NR 76 TC 115 Z9 119 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 MAY PY 1999 VL 73 IS 5 BP 4360 EP 4371 PG 12 WC Virology SC Virology GA 185ZG UT WOS:000079701100096 PM 10196334 ER PT J AU Brideau, AD Del Rio, T Wolffe, EJ Enquist, LW AF Brideau, AD Del Rio, T Wolffe, EJ Enquist, LW TI Intracellular trafficking and localization of the pseudorabies virus Us9 type II envelope protein to host and viral membranes SO JOURNAL OF VIROLOGY LA English DT Article ID HERPES-SIMPLEX VIRUS; TRANS-GOLGI NETWORK; VARICELLA-ZOSTER VIRUS; SHORT UNIQUE REGION; ENDOPLASMIC-RETICULUM MEMBRANE; GLUT4 GLUCOSE-TRANSPORTER; COMPLETE DNA-SEQUENCE; RAT VISUAL-SYSTEM; CYTOPLASMIC DOMAIN; GLYCOPROTEIN-I AB The Us9 protein is a phosphorylated membrane protein present in the lipid envelope of pseudorabies virus (PRV) particles in a unique tail-anchored type II membrane topology. In this report, we demonstrate that the steady-state residence of the Us9 protein is in a cellular compartment in or near the trans-Golgi network (TGN), Through internalization assays with an enhanced green fluorescent protein epitope-tagged Us9 protein, we demonstrate that the maintenance of Us9 to the TGN region is a dynamic process involving retrieval of molecules from the cell surface. Deletion analysis of the cytoplasmic tail reveals that an acidic cluster containing putative phosphorylation sites is necessary for the recycling of Us9 from the plasma membrane. The absence of this cluster results in the relocalization of Us9 to the plasma membrane due to a defect in endocytosis, The acidic motif, however, does not contain signals needed to direct the incorporation of Us9 into viral envelopes. In this study, we also investigate the role of a dileucine endocytosis signal in the Us9 cytoplasmic tail in the recycling and retention of Us9 to the TGN region. Site-directed mutagenesis of the dileucine motif results in an increase in Us9 plasma membrane staining and a partial internalization defect. C1 Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. NIAID, NIH, Bethesda, MD 20895 USA. RP Enquist, LW (reprint author), Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. EM Lenquist@molbiol.princeton.edu FU NIGMS NIH HHS [T32 GM007388, 5T32 GM07388]; PHS HHS [1RO133506] NR 70 TC 48 Z9 48 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 MAY PY 1999 VL 73 IS 5 BP 4372 EP 4384 PG 13 WC Virology SC Virology GA 185ZG UT WOS:000079701100097 PM 10196335 ER PT J AU Trus, BL Gibson, W Cheng, NQ Steven, AC AF Trus, BL Gibson, W Cheng, NQ Steven, AC TI Capsid structure of simian cytomegalovirus from cryoelectron microscopy: Evidence for tegument attachment sites (vol 73, pg 2181, 1999) SO JOURNAL OF VIROLOGY LA English DT Correction C1 NIAMS, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. CIT, Computat Biosci & Engn Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Virol Labs, Baltimore, MD 21205 USA. RP Trus, BL (reprint author), NIAMS, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. NR 1 TC 1 Z9 1 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 MAY PY 1999 VL 73 IS 5 BP 4530 EP 4531 PG 2 WC Virology SC Virology GA 185ZG UT WOS:000079701100124 ER PT J AU Rimer, BK Halabi, S Strigo, TS Crawford, Y Lipkus, IM AF Rimer, BK Halabi, S Strigo, TS Crawford, Y Lipkus, IM TI Confusion about mammography: Prevalence and consequences SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Article ID SCREENING GUIDELINES; BREAST-CANCER; STAGE AB Over the last decade, there has been significant controversy about the schedule on which women, particularly women in their 40s, should have mammograms. The purpose of the analysis reported here was to assess whether women in their 40s and 50s were confused as a result of the controversy following the January 1997 National Institutes of Health Consensus Development Conference on Breast Cancer Screening For Women Ages 40-49. We also examined if confusion was related to being off schedule for mammography. The study sample included 1287 women recruited from a random sample of 2165 Blue Cross/Blue Shield of North Carolina members. The data described in this analysis were derived from a baseline telephone interview conducted as part of a larger intervention trial. Study measures included a variety of sociodemographic, medical, belief, and behavioral variables. Overall, 28% of women were confused, and 35% were off schedule. Although a higher proportion of women in their 40s than 50s were confused, more women in their 50s were off schedule. Confusion was a significant predictor for the outcome being off schedule. Predictors of confusion included several belief variables, risk perceptions, age (40s), whether the woman had a regular physician, and whether she had enough information about mammography. Healthcare providers should ask some simple questions to determine if women are confused and then seek to meet their information needs. C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Community & Family Med, Div Biometry, Durham, NC 27710 USA. Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Canc Prevent Detect & Control Res Program, Durham, NC 27710 USA. RP Rimer, BK (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Plaza N,Room 242, Bethesda, MD 20892 USA. FU NCI NIH HHS [5U19-CA-72099-03] NR 21 TC 20 Z9 20 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1524-6094 J9 J WOMEN HEALTH GEN-B JI J. WOMENS HEALTH GENDER-BASED MED. PD MAY PY 1999 VL 8 IS 4 BP 509 EP 520 DI 10.1089/jwh.1.1999.8.509 PG 12 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 230ZN UT WOS:000082281700022 PM 10839706 ER PT J AU Metter, EJ Lynch, N Conwit, R Lindle, R Tobin, J Hurley, B AF Metter, EJ Lynch, N Conwit, R Lindle, R Tobin, J Hurley, B TI Muscle quality and age: Cross-sectional and longitudinal comparisons SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID X-RAY ABSORPTIOMETRY; SKELETAL-MUSCLE; ELDERLY MEN; REGRESSION-ANALYSIS; QUADRICEPS MUSCLES; BODY-COMPOSITION; STRENGTH; WOMEN; MASS; AREA AB We addressed whether muscle quality (force per unit muscle mass) changes with age in cross-sectional and longitudinal analyses from three groups from the Baltimore Longitudinal Study of Aging: (1) Isometric arm strength studied cross-sectionally in 617 subjects with muscle mass estimated by cross-sectional area (CSA)from arm circumference and by 24-hour urinary creatinine excretion (CREAT) (2) longitudinal study for 10 to 25 years in 412 men using the same measures as the first group; and (3) isometric knee extensor strength studied cross-sectionally in 675 subjects; muscle mass estimated by GREAT CSA from thigh circumference, and leg nonosseous fat free mass (FFM)from dual energy x-ray absorptiometry. Muscle quality declined in both arm and leg with age in cross-sectional analyses using GSA and FFM, but not GREAT No age-associated arm muscle quality declines were observed longitudinally using GREAT or GSA. The relationship between muscle quality and age is dependent on how muscle mass is estimated and on whether subjects are studied cross-sectionally or longitudinally. In addition, GREAT may measure a muscle property not accounted for by CSA or FFM. C1 NIA, Intramural Res Program, Gerontol Res Ctr, Baltimore, MD 21224 USA. Johns Hopkins Sch Med, Bayview Med Ctr, Dept Neurol, Baltimore, MD USA. Univ Maryland, Dept Kinesiol, College Pk, MD 20742 USA. RP Metter, EJ (reprint author), NIA, Intramural Res Program, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 49 TC 99 Z9 102 U1 1 U2 10 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 1999 VL 54 IS 5 BP B207 EP B218 DI 10.1093/gerona/54.5.B207 PG 12 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 200ZP UT WOS:000080570400007 PM 10362000 ER PT J AU Mannon, RB Kopp, JB Ruiz, P Griffiths, R Bustos, M Platt, JL Klotman, PE Coffman, TM AF Mannon, RB Kopp, JB Ruiz, P Griffiths, R Bustos, M Platt, JL Klotman, PE Coffman, TM TI Chronic rejection of mouse kidney allografts SO KIDNEY INTERNATIONAL LA English DT Article DE transplantation; renal graft rejection; TGF-beta; fibrosis; mouse MHC; arteriosclerosis; glomerulosclerosis ID GROWTH-FACTOR-BETA; CHRONIC CARDIAC REJECTION; TRANSPLANT ARTERIOSCLEROSIS; T-CELL; MACROPHAGE ACTIVATION; DEFICIENT MICE; UP-REGULATION; TGF-BETA; EXPRESSION; MODEL AB Background Chronic renal allograft rejection is the leading cause of late graft failure. However, its pathogenesis has not been defined. Methods. To explore the pathogenesis of chronic rejection, we studied a mouse model of kidney transplantation and examined the effects of altering the expression of donor major histocompatibility complex (MHC) antigens on the development of chronic rejection. Results. We found that long-surviving mouse kidney allografts develop pathological abnormalities that resemble chronic rejection in humans. Furthermore, the absence of MHC class I or class II antigens did not prevent the loss of graft function nor alter the pathological characteristics of chronic rejection. Expression of transforming growth factor-beta (TGF-beta), a pleiotropic cytokine suggested to play a role in chronic rejection, was markedly enhanced in control allografts compared with isografts. However, TGF-beta up-regulation was significantly blunted in MHC-deficient grafts. Nonetheless, these differences in TGF-beta expression did not affect the character of chronic rejection, including intrarenal accumulation of collagens. Conclusions. Reduced expression of either class I or II direct allorecognition pathways is insufficient to prevent the development of chronic rejection, despite a reduction in the levels of TGF-beta expressed in the allograft. This suggests that the severity of chronic rejection is independent of the level of MHC disparity between donor and recipient and the level of TGF-beta expression within the allograft. C1 VA Med Ctr, Nephrol Sect 1111, Dept Med, Durham, NC 27705 USA. VA Med Ctr, Dept Pediat, Durham, NC 27705 USA. VA Med Ctr, Dept Immunol, Durham, NC 27705 USA. Duke Univ, Dept Med, Durham, NC USA. Duke Univ, Dept Pediat, Durham, NC 27706 USA. Duke Univ, Dept Immunol, Durham, NC 27706 USA. NIDDK, NIH, Bethesda, MD USA. Univ Miami, Med Ctr, Dept Pathol, Miami, FL 33152 USA. Mt Sinai Sch Med, Dept Med, New York, NY USA. RP Mannon, RB (reprint author), VA Med Ctr, Nephrol Sect 1111, Dept Med, 508 Fulton St, Durham, NC 27705 USA. OI Kopp, Jeffrey/0000-0001-9052-186X FU NIAID NIH HHS [1 K08 AI01389-01]; NIDDK NIH HHS [P01-DK38103] NR 39 TC 45 Z9 48 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 1999 VL 55 IS 5 BP 1935 EP 1944 DI 10.1046/j.1523-1755.1999.00423.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 188LZ UT WOS:000079849600030 PM 10231457 ER PT J AU Ojo, AO Hanson, JA Wolfe, RA Agodoa, LY Leavey, SF Leichtman, A Young, EW Port, FK AF Ojo, AO Hanson, JA Wolfe, RA Agodoa, LY Leavey, SF Leichtman, A Young, EW Port, FK TI Dialysis modality and the risk of allograft thrombosis in adult renal transplant recipients SO KIDNEY INTERNATIONAL LA English DT Article DE kidney transplantation; renal graft; uremic coagulopathy; hemodialysis; perioperative anticoagulation; vascular thrombosis ID AMBULATORY PERITONEAL-DIALYSIS; BLOOD-PRESSURE CONTROL; VASCULAR THROMBOSIS; GRAFT THROMBOSIS; CYCLOSPORINE IMMUNOSUPPRESSION; KIDNEY-TRANSPLANTATION; ANTITHROMBIN-III; HEMODIALYSIS; CAPD; COMPLICATIONS AB Background. Renal vascular thrombosis (RVT) is a rare but catastrophic complication of renal transplantation. Although a plethora of risk factors has been identified, a large proportion of cases of RVT is unexplained. Uremic coagulopathy and dialysis modality may predispose to RVT. We investigated the impact of the pretransplant dialysis modality on the risk of RVT in adult renal transplant recipients. Methods. Renal transplant recipients (age 18 years or more) who were enrolled in the national registry between 1990 and 1996 (N = 84,513) were evaluated for RVT occurring within 30 days of transplantation. Each case was matched with two controls from the same transplant center and with the year of transplantation. The association between RVT and 18 factors was studied with multivariate conditional logistic regression. Results. Forty-nine percent of all cases of RVT (365 out of 743) occurred in repeat transplant recipients with an adjusted odds ratio (OR) of 5.72 compared with first transplants (P < 0.001). There were a significantly higher odds of RVT in peritoneal dialysis (PD)-compared with hemodialysis (HD)-treated patients (OR = 1.87, P = 0.001). Change in dialysis modality was an independent predictor of RVT: switching from IID to PD (OR = 3.59, P < 0.001) and from PD to HD (OR = 1.62, P = 0.047). Compared with primary transplant recipients on HD (OR = 1.00), the highest odds of RVT were in repeat transplant recipients treated with PD (OR = 12.95, P < 0.001) and HD (OR = 4.50, P < 0.001). Other independent predictors of RVT were preemptive transplantation, relatively young and old donor age, diabetes mellitus and systemic lupus erythematosus as causes of end-stage renal disease, recipient gender, and lower panel reactive antibody levels (PRAs). Conclusions. The strongest risk factors for RVT were retransplantation and prior PD treatment. Prevention of RVT with perioperative anticoagulation should be studied in patients who have a constellation of the identified risk factors. C1 Univ Michigan, Vet Adm Hosp, Dept Med, Ann Arbor, MI 48109 USA. Univ Michigan, Vet Adm Hosp, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Michigan, Vet Adm Hosp, Dept Epidemiol, Ann Arbor, MI 48109 USA. NIDDKD, US Renal Data Syst, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. RP Ojo, AO (reprint author), Univ Michigan, Med Ctr, Dept Internal Med, Div Nephrol, TC 3914,Box 0364, Ann Arbor, MI 48109 USA. NR 62 TC 50 Z9 52 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 1999 VL 55 IS 5 BP 1952 EP 1960 DI 10.1046/j.1523-1755.1999.00435.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 188LZ UT WOS:000079849600032 PM 10231459 ER PT J AU Matsukawa, A Yoshimura, T Fujiwara, K Maeda, T Ohkawara, S Yoshinaga, M AF Matsukawa, A Yoshimura, T Fujiwara, K Maeda, T Ohkawara, S Yoshinaga, M TI Involvement of growth-related protein in lipopolysaccharide-induced rabbit arthritis: Cooperation between growth-related protein and IL-8, and interrelated regulation among TNF alpha, IL-1, IL-1 receptor antagonist, IL-8, and growth-related protein SO LABORATORY INVESTIGATION LA English DT Article ID TUMOR-NECROSIS-FACTOR; MONOCYTE CHEMOATTRACTANT PROTEIN-1; NEUTROPHIL CHEMOTACTIC FACTOR; AMINO-ACID-SEQUENCE; STIMULATORY ACTIVITY; VASCULAR-PERMEABILITY; CYTOKINE NETWORK; INDUCED PLEURISY; IN-VIVO; CHEMOKINES AB We investigated the functional role of a CXC chemokine, growth-related protein (GRO), in the recruitment of neutrophils in lipopolysaccharide (LPS)-induced rabbit arthritis. The amounts of GRO in the synovial fluids (SF) reached the first peak (major) at 2 hours and the second peak (minor) at 9 hours after injection of LPS into the knee joints. Administration of anti-GRO mouse monoclonal antibody inhibited 54% of the peak leukocyte accumulation at 9 hours (neutrophils greater than 95%), which was similar to the inhibition by anti-IL-8 IgG (48%). Co-administration of these inhibitors increased the inhibition up to 70% at 9 hours and also inhibited 65% of the initial phase of leukocyte infiltration at 2 hours (neutrophils greater than 99%), which was not affected by a single administration of each inhibitor. The amounts of GRO in SF at 2 hours were not altered by either anti-TNF alpha mAb or anti-IL-8 IgG, but reduced by rabbit recombinant IL-l receptor antagonist (rrIL-1Ra) by 39%. The inhibition by rrIL-1Ra was augmented further to 59% with coadministered anti-TNFa mAb. In contrast, the amounts of GRO at 9 hours were reduced by rrIL-1Ra by 67%. There was no additional reduction in the amounts of GRO at 9 hours by either combination of rrIL-1Ra with anti-TNF alpha mAb or anti-IL-8 IgG. Administration of anti-GRO mAb did not alter TNF alpha or IL-8 contents in SF at their peak (2 hours), but reduced the amounts of IL-beta at 6 hours and IL-1Ra at 9 hours by 42% and 49%, respectively. These results provide evidence for the following: (a) GRO as well as IL-8 are important mediators involved in the recruitment of neutrophils both in the early and the late phase of LPS-induced arthritis, (b) IL-l produced in the early phase stimulates GRO production, (9) GRO plays a role in the later induction of IL-1 beta and IL-1Ra, and (d) induction of GRO is not regulated by IL-8. C1 Kumamoto Univ, Sch Med, Dept Pathol, Kumamoto 8600811, Japan. NCI, Frederick Canc Res & Dev Ctr, Immunopathol Sect, Immunol Lab, Frederick, MD USA. RP Yoshinaga, M (reprint author), Kumamoto Univ, Sch Med, Dept Pathol, 2-2-1 Honjo, Kumamoto 8600811, Japan. NR 40 TC 25 Z9 27 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAY PY 1999 VL 79 IS 5 BP 591 EP 600 PG 10 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 196TY UT WOS:000080324700009 PM 10334570 ER PT J AU Gottschalk, WA Jiang, H Tartaglia, N Feng, LY Figurov, A Lu, B AF Gottschalk, WA Jiang, H Tartaglia, N Feng, LY Figurov, A Lu, B TI Signaling mechanisms mediating BDNF modulation of synaptic plasticity in the hippocampus SO LEARNING & MEMORY LA English DT Article ID LONG-TERM POTENTIATION; NERVE GROWTH-FACTOR; ACTIVATED PROTEIN-KINASE; DEVELOPING NEUROMUSCULAR SYNAPSES; CILIARY NEUROTROPHIC FACTOR; CORTICAL DENDRITIC GROWTH; VISUAL-CORTEX; PHOSPHATIDYLINOSITOL 3-KINASE; TRK PROTOONCOGENE; DEVELOPING MOTONEURONS AB Although recent studies indicate that brain-derived neurotrophic factor (BDNF) plays an important role in hippocampal synaptic plasticity, the underlying signaling mechanisms remain largely unknown. Here, we have characterized the signaling events that mediate the BDNF modulation of high-frequency synaptic transmission. Mitogen-associated protein kinase (MAPK), phosphotidylinositol-3 kinase (PI3K), and phospholipase C-gamma (PLC-gamma) are the three signaling pathways known to mediate neurotrophin signaling in other systems. In neonatal hippocampal slices, application of BDNF rapidly activated MAPK and PI3K but not PLC-gamma. BDNF greatly attenuated synaptic fatigue at CA1 synapses induced by a train of high-frequency, tetanic stimulation (HFS). Inhibition of the MAPK and. PI3K, but not PLC-gamma, prevented the BDNF modulation of high-frequency synaptic transmission. Neurotrophin-3 (NT-3), a close relative of BDNF, did not activate MAPK or PI3K and had no effect on synaptic fatigue in the neonatal hippocampus. Neither forskolin, which activated MAPK but not PIS kinase, nor ciliary neurotrophic factor (CNTF), which activated PI3K but not MAPK, affected HFS-induced synaptic fatigue. Treatment of the slices with forskolin together with CNTF still had no effect on synaptic fatigue. Thus, although the activation of MAPK and PI3K is required, the two together are not sufficient to mediate the BDNF effect. Inhibition of new protein synthesis by anisomycin or cycloheximide did not prevent the BDNF effect. These data suggest that BDNF modulation of high-frequency transmission is independent of protein synthesis but requires MAPK and PI3K and yet another signaling pathway to act together in the hippocampus. C1 NICHD, Unit Synapse Dev & Plast, NIH, Bethesda, MD 20892 USA. Chinese Acad Sci, Shanghai Res Ctr Life Sci, Shanghai 200031, Peoples R China. Chinese Acad Sci, Shanghai Brain Res Inst, Shanghai 200031, Peoples R China. Howard Hughes Med Inst, NIH, Res Scholars Program, Bethesda, MD 20829 USA. NICHD, Growth Factors Sect, Bethesda, MD 20829 USA. RP Lu, B (reprint author), NICHD, Unit Synapse Dev & Plast, NIH, Bethesda, MD 20892 USA. RI Lu, Bai/A-4018-2012 NR 79 TC 107 Z9 107 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1072-0502 J9 LEARN MEMORY JI Learn. Mem. PD MAY-JUN PY 1999 VL 6 IS 3 BP 243 EP 256 PG 14 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 232YB UT WOS:000082396600004 PM 10492006 ER PT J AU Heerema, NA Sather, HN Ge, J Arthur, DC Hilden, JM Trigg, ME Reaman, GH AF Heerema, NA Sather, HN Ge, J Arthur, DC Hilden, JM Trigg, ME Reaman, GH TI Cytogenetic studies of infant acute lymphoblastic leukemia: poor prognosis of infants with t(4;11) - a report of the Children's Cancer Group SO LEUKEMIA LA English DT Article DE infant leukemia; acute lymphoblastic leukemia; t(4;11)(q21;q23); chromosome 11q23 ID MLL-GENE REARRANGEMENTS; PROLINE-RICH PROTEIN; MOLECULAR ANALYSIS; CHROMOSOME-TRANSLOCATION; CLINICAL-SIGNIFICANCE; 11Q23 REARRANGEMENTS; MYELOID LEUKEMIAS; ALL-1 GENE; ABNORMALITIES; HRX AB Infants less than 1 year of age at diagnosis of acute lymphoblastic leukemia (ALL) have a poor prognosis, which has been attributed primarily to a breakpoint in chromosomal band 11q23 or the MLL gene. Most infants with an 11q23 breakpoint have a t(4;11)(q21;q23). We studied the cytogenetics of the leukemia cells of 56 infants on CCG-1883, a single-arm clinical treatment protocol for infant ALL. Twenty-one patients had t(4;11)(q21;q23), seven had other rearrangements with breakpoints in 11q23 (other 11q23), 16 had normal chromosomes, two had t(1;19)(q32;p13), one had >50 chromosomes, and nine had non-recurring structural abnormalities. To determine whether there is a difference in outcome for infants with t(4;11), other 11q23 and the remaining patients, we compared event-free survival (EFS) and other clinical and laboratory features of the above infants. Infants without 1(4;11) and those with other 11q23 rearrangements had significantly better EFS than those with t(4;11) (P = 0.007 and P = 0.02, respectively), t(4;11) correlated with age less than 6 months and with CD10 negativity, both of which also were poor prognostic indicators. After adjustment for age, there was still a significant difference in EFS between patients with t(4;11) and those with other 11q23 rearrangements (P = 0.02), and between patients with t(4;11) and those without t(4;11) (P = 0.04). Among CD10 negative patients, t(4;11) was associated with a worse EFS (P = 0.01). Multivariate analysis showed that after adjusting for a variety of clinical and laboratory features, t(4;11) was the most important prognostic factor for poor outcome, and patients with other 11q23 rearrangements had as good an outcome as the remaining patients without t(4;11). C1 Childrens Canc Grp, Grp Operat Ctr, Arcadia, CA 91066 USA. Howard Hughes Med Inst, St Paul, MN USA. Univ So Calif, Los Angeles, CA USA. NCI, Bethesda, MD 20892 USA. Childrens Hosp & Clin, St Paul, MN USA. Dupont Inst, Wilmington, DE USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. George Washington Univ, Sch Med, Washington, DC USA. RP Heerema, NA (reprint author), Childrens Canc Grp, Grp Operat Ctr, POB 60012, Arcadia, CA 91066 USA. NR 42 TC 73 Z9 73 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 1999 VL 13 IS 5 BP 679 EP 686 DI 10.1038/sj.leu.2401413 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 195MB UT WOS:000080253800004 PM 10374870 ER PT J AU Corn, M AF Corn, M TI First projects: Healthcare rules! SO M D COMPUTING LA English DT Article C1 Natl Lib Med, Bethesda, MD 20209 USA. RP Corn, M (reprint author), Natl Lib Med, Bethesda, MD 20209 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0724-6811 J9 M D COMPUT JI M D Comput. PD MAY-JUN PY 1999 VL 16 IS 3 BP 23 EP + PG 3 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA 220BA UT WOS:000081643200012 PM 10439595 ER PT J AU Silva, JS AF Silva, JS TI Fighting cancer in the information age - An architecture for national scale clinical trials SO M D COMPUTING LA English DT Article C1 NCI, Off Informat, Bethesda, MD 20892 USA. RP Silva, JS (reprint author), NCI, Off Informat, Bethesda, MD 20892 USA. NR 0 TC 9 Z9 10 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0724-6811 J9 M D COMPUT JI M D Comput. PD MAY-JUN PY 1999 VL 16 IS 3 BP 43 EP 44 PG 2 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA 220BA UT WOS:000081643200018 PM 10439600 ER PT J AU Warren, JL Feuer, E Potosky, AL Riely, GF Lynch, CF AF Warren, JL Feuer, E Potosky, AL Riely, GF Lynch, CF TI Use of Medicare hospital and physician data to assess breast cancer incidence SO MEDICAL CARE LA English DT Article DE breast neoplasms; incidence; SEER; Medicare; epidemiologic methods ID CLAIMS DATA; ELDERLY AMERICANS; OUTPATIENT; SURGERY; MASTECTOMY AB OBJECTIVES. Health claims data have the potential of being an inexpensive, timely, and nationally representative source of information about cancer. This study examined the utility of Medicare hospital and physician data as an independent source to identify incident breast cancer cases. METHODS. Data came from Medicare and the National Cancer Institute's SEER cancer registries. From 1992, for women residing in the SEER states (n = 659,260), Medicare hospital and physician claims were reviewed to identify women with a breast cancer diagnosis on a claim (n = 6,784). These women were matched with women in the SEER data who had been diagnosed with breast canter in 1992 (n = 3,230). The sensitivity, specificity, and positive predictive value (PPV) of the Medicare data were calculated Logistic regression models were used to identified cancer related procedures reported to Medicare that could distinguish true cases from false positive cases. Predicted values from these models were included to create plots of sensitivity versus false positive rates and sensitivity versus PPV. RESULTS. Medicare hospital data had 62% sensitivity, 99.9% specificity, and 88% PPV. Physician claims increased sensitivity by 14%, with specificity of 99.4%, and a PPV of 10%. Inclusion of additional cancer related diagnoses and procedures improved the ability to distinguish true cases from false positives, although the number of false positive cases remained high. CONCLUSIONS. The Medicare data overall offer limited potential to assess breast cancer incidence, largely because of low sensitivity and poor PPV. The Medicare data may have utility to identify women undergoing selected breast cancer treatments. In addition, the data may be used to help registries focus case-finding efforts, particularly for persons undergoing cancer related treatments. C1 NCI, Appl Res Branch, Bethesda, MD 20892 USA. US Hlth Care Financing Adm, Baltimore, MD 21207 USA. Univ Iowa, Dept Prevent Med & Environm Hlth, Iowa City, IA 52242 USA. RP Warren, JL (reprint author), NCI, Appl Res Branch, Execut Plaza N,Room 313,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 25 TC 78 Z9 78 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAY PY 1999 VL 37 IS 5 BP 445 EP 456 DI 10.1097/00005650-199905000-00004 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 195UQ UT WOS:000080270900004 PM 10335747 ER PT J AU Bottner, A Eisenhofer, G Torpy, DJ Ehrhart-Bornstein, M Keiser, HR Chrousos, GP Bornstein, SR AF Bottner, A Eisenhofer, G Torpy, DJ Ehrhart-Bornstein, M Keiser, HR Chrousos, GP Bornstein, SR TI Lack of leptin suppression in response to hypersecretion of catecholamines in pheochromocytoma patients SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID BROWN ADIPOCYTES; NORMAL-WEIGHT; EXPRESSION; SECRETION; INHIBITION; HUMANS; ACID; OB AB Leptin is a major regulator of body weight and energy balance and is subject to a variety of regulatory inputs. From several previous studies, catecholamines have been suggested to exert an inhibitory influence on leptin production in animals. In the present study, we analyzed leptin levels in relation to catecholamine hypersecretion in 27 human pheochromocytoma patients. A 10-fold increase in circulating norepinephrine (P < .0001) did not result in suppression of plasma leptin in the patients compared with normal controls (median and interquartile range, 4.3 ng/mL [2.4 to 6.8] v 2.2 ng/mL [1.9 to 3.0] in men and 18.6 [12.3 to 27.0] v 11.4 [10.1 to 15.9] in women). Correlation analysis indicated a significant association of leptin with epinephrine in normal subjects (r = -.81, P < .0001), but not in pheochromocytoma patients. Leptin was not related to norepinephrine in either group. In conclusion, our data suggest that a chronic elevation of catecholamines does not cause suppression of leptin secretion in patients with pheochromocytoma. This lack of effect may be attributable to the development of tolerance of adipose tissue leptin production to catecholamines. Copyright (C) 1999 by W.B. Saunders Company. C1 Univ Leipzig, Dept Internal Med 3, D-04103 Leipzig, Germany. NINDS, Intramural Res Program, Bethesda, MD 20892 USA. NHLBI, Hypertens Endocrine Branch, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. Univ Adelaide, Queen Elizabeth Hosp, Adelaide, SA, Australia. RP Bottner, A (reprint author), Univ Leipzig, Dept Internal Med 3, PH Rosenthal Str 27, D-04103 Leipzig, Germany. RI Korner, Antje/B-3988-2015 OI Korner, Antje/0000-0001-6001-0356 NR 19 TC 23 Z9 23 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD MAY PY 1999 VL 48 IS 5 BP 543 EP 545 DI 10.1016/S0026-0495(99)90047-1 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 194YB UT WOS:000080221400001 PM 10337850 ER PT J AU Marcell, TJ Wiswell, RA Hawkins, SA Tarpenning, KM AF Marcell, TJ Wiswell, RA Hawkins, SA Tarpenning, KM TI Age-related blunting of growth hormone secretion during exercise may not be solely due to increased somatostatin tone SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID RESISTANCE EXERCISE; CHOLINERGIC TONE; RESPONSES; MEN; PYRIDOSTIGMINE; INVOLVEMENT; RELEASE AB Age-related declines in growth hormone (GH) secretion may result from augmented somatostatin (SRIH) tone and/or diminished GH-releasing hormone (GHRH) secretion. We assessed GH release during exercise without and with pyridostigmine (PYR), which indirectly suppresses SRIH. GH levels were measured throughout exercise and recovery in 12 young men (mean +/- SEM, 20.8 +/- 0.4 years) and seven old men (66.1 +/- 1.9), The area under the GH curve (GH-AUC) was greater in young versus old men during a short-term maximal exercise test (12.9 +/- 2.8 v 1.5 +/- 0.2 ng.min(-1).mL(-1), P = .002) and a 1-hour 60% maximal (submaximal, 10.0 +/- 1.5 v 3.0 +/- 1.0 ng.min(-1).mL(-1), P = .001) cycle exercise bout. PYR increased the GH-AUC in young and old men during maximal (20.9 +/- 5.2 v 4.9 +/- 1.8) and submaximal (12.3 +/- 1.6 v 4.7 +/- 1.5) exercise (P < .05). The greater GH response to maximal versus submaximal exercise suggests a role for adrenergic modulation of GHRH during exercise. However, the failure of PYR to restore the responses of the old to those of the young suggests that increased SRIH tone does not completely explain the age difference in GH secretion during exercise. Copyright (C) 1999 by W.B. Saunders Company. C1 Univ So Calif, Dept Exercise Sci, Los Angeles, CA USA. RP Marcell, TJ (reprint author), NIA, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr,Box 14, Baltimore, MD 21224 USA. NR 25 TC 18 Z9 18 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD MAY PY 1999 VL 48 IS 5 BP 665 EP 670 DI 10.1016/S0026-0495(99)90069-0 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 194YB UT WOS:000080221400023 PM 10337872 ER PT J AU Middleton, LP Tressera, F Sobel, ME Bryant, BR Alburquerque, A Grases, P Merino, MJ AF Middleton, LP Tressera, F Sobel, ME Bryant, BR Alburquerque, A Grases, P Merino, MJ TI Infiltrating micropapillary carcinoma of the breast SO MODERN PATHOLOGY LA English DT Article DE breast; carcinoma; immunohistochemistry; loss of heterozygosity; micropapillary ID P53 GENE; CANCER; PROGNOSIS AB Infiltrating micropapillary carcinoma of the breast is a recently described and poorly recognized aggressive variant of infiltrating ductal carcinoma for which the clinical significance and role of prognostic markers are not fully described. In 14 cases of infiltrating micropapillary carcinoma, we studied histologic characteristics; immunohistochemical expression of c-erbB-2, p53, and MIB-1; hormonal expression of these tumors; and genetic alterations on the p53 locus. We correlated these results with clinical outcome. Patient ages ranged from 37 to 58 years (mean, 50 yr). Nine patients presented with a palpable tumor, one with an axillary mass. Three patients had abnormal mammograms. Five patients (36%) presented with Stage II disease, eight (57%) with Stage III, and one (7%) with Stage IV. The tumors were a modified Bloom-Richardson Grade II in nine cases (64%) and Grade III in 5 (36%). Mitoses ranged from 1 to 12 per 10 high power fields. Necrosis was uniformly absent. Psammoma bodies were present in 9 cases (64%) and lymphatic invasion in 10 (71%). In all of the cases, c-erbB-2 was identified immunohistochemically, and MIB-1 was positive, staining 30 to 60% of the tumor cells. The cells were immunoreactive for p53 in six (75%) of eight cases, and, when present, stained 20 to 50% of the tumor cells. Loss of heterozygosity on locus 17p13.1 (p53) was identified in 4 of 5 informative samples. Molecular and immunohistochemical analyses had an 80% concordance. Follow-up was available in 11 patients, of whom 9 had recurrence in the skin and chest wall (average time of recurrence, 24 mo). Recognition of this distinctive and aggressive variant of infiltrating carcinoma is important because of its unfavorable prognosis and specific pattern of local recurrence. Its aggressive nature is supported by its advanced stage at presentation and expression of unfavorable prognostic markers. C1 NCI, Bethesda, MD 20892 USA. Inst Dexeus, Barcelona, Spain. RP Middleton, LP (reprint author), Pathol Lab, Bldg 10,Room 2N212,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 14 TC 56 Z9 74 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAY PY 1999 VL 12 IS 5 BP 499 EP 504 PG 6 WC Pathology SC Pathology GA 197CK UT WOS:000080346900010 PM 10349988 ER PT J AU Srivastava, RK Srivastava, AR Seth, P Agrawal, S Cho-Chung, YS AF Srivastava, RK Srivastava, AR Seth, P Agrawal, S Cho-Chung, YS TI Growth arrest and induction of apoptosis in breast cancer cells by antisense depletion of protein kinase A-RI alpha subunit: p53-independent mechanism of action SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE antisense oligonucleotide; apoptosis; cAMP-dependent protein kinase; cancer cells; growth inhibition ID REGULATORY SUBUNIT; P53; GENE; DIFFERENTIATION; BCL-2; OLIGODEOXYNUCLEOTIDE; OLIGONUCLEOTIDES; IDENTIFICATION; SUPPRESSION; ACTIVATION AB The enhanced expression of the RI alpha subunit of cyclic AMP-dependent protein kinase type 1 (PKA-I) has been correlated with cancer cell growth. We have investigated the effects of sequence-specific inhibition of RI alpha gene expression on the growth of MCF-7 human breast cancer cells. We report that RI alpha antisense treatment results in a reduction in RI alpha expression at both mRNA and protein levels and inhibition of cell growth. The growth inhibition was accompanied by changes in cell morphology, cleavage of poly(ADP-ribose) polymerase (PARP) and appearance of apoptotic nuclei. In addition, bcl-2 protein level was reduced and p53 expression increased in growth arrested cells. Interestingly, RI alpha antisense inhibited cell viability and induced apoptosis in the absence of p53, suggesting that these actions of RI alpha antisense are exerted independent of p53. In contrast, two- and four-base mismatched control oligonucleotides had no effect on either cell growth or morphology. These results demonstrate that the RI alpha antisense, which efficiently depletes the growth stimulatory molecule RI alpha, induces cell differentiation and apoptosis, providing a new approach to combat breast cancer cell growth. C1 NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. Hybridon Inc, Milford, MA USA. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, NIH, Bldg 10,Room 5B05, Bethesda, MD 20892 USA. NR 39 TC 33 Z9 35 U1 1 U2 2 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 MAY PY 1999 VL 195 IS 1-2 BP 25 EP 36 DI 10.1023/A:1006990231186 PG 12 WC Cell Biology SC Cell Biology GA 203LV UT WOS:000080709900004 PM 10395066 ER PT J AU Lee, GR Kim, SN Noguchi, K Park, SD Hong, SH Cho-Chung, YS AF Lee, GR Kim, SN Noguchi, K Park, SD Hong, SH Cho-Chung, YS TI Ala(99)ser mutation in RI alpha regulatory subunit of protein kinase A causes reduced kinase activation by cAMP and arrest of hormone-dependent breast cancer cell growth SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE protein kinase A; site-directed mutagenesis; breast cancer; growth arrest; cAMP response element ID MAMMARY EPITHELIAL-CELLS; HL-60 LEUKEMIA-CELLS; AMINO-ACID SEQUENCE; HUMAN TESTIS; AUTOPHOSPHORYLATION SITE; MOLECULAR-CLONING; BETA-SUBUNIT; DIFFERENTIATION; FIBROBLASTS; OVEREXPRESSION AB Expression of the RIalpha regulatory subunit of protein kinase A type I is increased in human cancer cell lines, in primary tumors, in cells after transformation, and in cells upon stimulation of growth. Ala99 (the pseudophosphorylation site) of human RIalpha was replaced with Ser (RIalpha-p) for the structure-function analysis of RIalpha. MCF-7 hormone- dependent breast cancer cells were transfected with an expression vector for the wild-type RIalpha or mutant RIalpha-p. Overexpression of RIalpha-P resulted in suppression of protein kinase A type II, the isozyme of type I kinase, production of kinase exhibiting reduced cAMP activation, and inhibition of cell growth showing an increase in G(0)/G(1) phase of the cell cycle and apoptosis. The wild-type RIalpha overexpression had no effect on protein kinase A isozyme distribution or cell growth. Overexpression of protein kinase A type II regulatory subunit, RIIbeta, suppressed RIalpha and protein kinase A type I and inhibited cell growth. These results show that the growth of hormone-dependent breast cancer cells is dependent on the functional protein kinase A type I. C1 NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. Seoul Natl Univ, Dept Mol Biol, Seoul, South Korea. Seoul Natl Univ, Res Ctr Cell Differentiat, Seoul, South Korea. Seoul Natl Univ, Inst Mol Biol & Genet, Seoul, South Korea. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, Bldg 10,Room 5N05, Bethesda, MD 20892 USA. NR 33 TC 13 Z9 14 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD MAY PY 1999 VL 195 IS 1-2 BP 77 EP 86 DI 10.1023/A:1006934113439 PG 10 WC Cell Biology SC Cell Biology GA 203LV UT WOS:000080709900009 PM 10395071 ER PT J AU Putilina, T Wong, P Gentleman, S AF Putilina, T Wong, P Gentleman, S TI The DHHC domain: A new highly conserved cysteine-rich motif SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE protein-protein interactions; zinc fingers; nuclear export signal ID DNA-BINDING DOMAIN; ZINC-FINGER; LIM DOMAIN; STRUCTURAL MOTIF; PROTEINS; IDENTIFICATION; RECOGNITION; NUCLEUS; COMPLEX AB A unique clone from a human pancreatic cDNA library was isolated and sequenced. Examination of the deduced polypeptide sequence of the clone showed a new form of cysteine-rich domain that included a region with the form of a Cys4 zinc-finger-like metal binding site followed by a complex Cys-His region. Searches of the Swiss-Protein data bank found a similar 48-residue domain in fifteen open reading frames deduced from A. thaliana, C. elegans, S. cerevisiae and S. pombe genomic sequences. The high degree of conservation of this domain (13 absolutely conserved and 17 highly conserved positions) suggests that it has an important function in the cell, possibly related to protein-protein or protein-DNA interactions. The gene recognized by the clone is is localized to human chromosome 16, and is conserved in vertebrates. The 2 Kb message is expressed in various human fetal and adult tissues. An antibody made to a peptide sequence of the deduced protein showed reactivity in immunoblots of monkey lung and retinal subcellular fractions and immunohistochemically in late fetal mouse tissues and a limited number of adult mouse tissues, including pancreatic islets, Leydig cells of the testis, and the plexiform layers of the retina. C1 NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Alberta, Dept Biol Sci, Edmonton, AB, Canada. RP Putilina, T (reprint author), Bldg 6,Room 335,6 Ctr Dr,MSC 2740, Bethesda, MD USA. NR 21 TC 72 Z9 77 U1 0 U2 4 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 MAY PY 1999 VL 195 IS 1-2 BP 219 EP 226 DI 10.1023/A:1006932522197 PG 8 WC Cell Biology SC Cell Biology GA 203LV UT WOS:000080709900024 PM 10395086 ER PT J AU Herrera, JE Sakaguchi, K Bergel, M Trieschmann, L Nakatani, Y Bustin, M AF Herrera, JE Sakaguchi, K Bergel, M Trieschmann, L Nakatani, Y Bustin, M TI Specific acetylation of chromosomal protein HMG-17 by PCAF alters its interaction with nucleosomes SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HISTONE ACETYLTRANSFERASE ACTIVITY; MOBILITY GROUP PROTEIN-14; RNA-POLYMERASE-II; TRANSCRIPTIONAL REPRESSION; CHROMATIN STRUCTURE; BINDING DOMAIN; H4; DEACETYLATION; SINGLE; CORES AB Nonhistone chromosomal proteins HMG-14 and HMG-17 are closely related nucleosomal binding proteins that unfold the higher-order chromatin structure, thereby enhancing the transcription and replication potential of chromatin. Here we report that PCAF, a transcription coactivator with intrinsic histone acetyltransferase activity, specifically acetylates HMG-17 but not HMG-14. Using mass spectrum sequence analysis, we identified the lysine at position 2 as the predominant site acetylated by PCAF. Lysine 2 is a prominent acetylation site in vivo, suggesting that this PCAF-mediated acetylation is physiologically relevant. Experiments with HMG-17 deletion mutants and competition studies with various protein fragments indicate that the specific acetylation of HMG-17 is not determined solely by the primary sequence near the acetylation site. By equilibrium dialysis we demonstrated that acetylation reduces the affinity of HMG-17 to nucleosome cores. In addition, we found that the binding of HMG-14 and HMG-17 to nucleosome cores inhibits the PCAF-mediated acetylation of histone H3. Thus, the presence of HMG-14 and HMG-17 affects the ability of PCAF to acetylate chromatin, while the acetylation of HMG-17 reduces its binding affinity to chromatin. Conceivably, in HMG-17-containing chromatin, acetylation of HMG-17 precedes the acetylation of histones. C1 NCI, Prot Sect, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NCI, Chem Sect, Cell Biol Lab, Div Basic Sci,NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Herrera, JE (reprint author), NCI, Prot Sect, Mol Carcinogenesis Lab, NIH, Bldg 37,Rm 3D-20, Bethesda, MD 20892 USA. RI Bustin, Michael/G-6155-2015 NR 53 TC 71 Z9 71 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 MAY PY 1999 VL 19 IS 5 BP 3466 EP 3473 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 188AJ UT WOS:000079821100023 PM 10207070 ER PT J AU Soon, L Flechner, L Gutkind, JS Wang, LH Baserga, R Pierce, JH Li, WQ AF Soon, L Flechner, L Gutkind, JS Wang, LH Baserga, R Pierce, JH Li, WQ TI Insulin-like growth factor I synergizes with interleukin 4 for hematopoietic cell proliferation independent of insulin receptor substrate expression SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID KINASE-C-DELTA; ACTIVATED PROTEIN-KINASE; SIGNAL-TRANSDUCTION; TYROSINE PHOSPHORYLATION; HUMAN KERATINOCYTES; COMMON ELEMENTS; SHC; PATHWAYS; SYSTEM; DIFFERENTIATION AB In the present study, we investigated the potential role of insulin-like growth factor I (IGF-I) receptor (IGF-IR) in cell proliferation by overexpressing it in 32D myeloid progenitor cells. The overexpression of IGF-IR caused the transfectants to proliferate in response to IGF-I in the absence of insulin receptor substrate (IRS) expression, The activation of overexpressed wild-type IGF-IR, but not that of an ATP-binding mutant of IGF-IR, resulted in the increased tyrosine phosphorylation of several intracellular proteins, including SHC, Src homology 2-containing inositol-5-phosphatase, protein kinase C-delta, and Erk2, Grb2 association with SHC and mitogen-activated protein kinase (MAPK) activity was also enhanced in response to IGF-I stimulation. Interestingly, the stimulation of the IGF-IR transfectants with interleukin 4 (IL-4) also resulted in strong mitogenesis independent of IRS expression. Moreover, IGF-I and/or IL-4 induced long-term cell growth of the IGF-IR transfectants. IL-4 was able to synergize with IGF-I for DNA synthesis, even in the parental 32D cells and a pro-B-cell line, Baf3, indicating the physiological importance of the two growth factors in hematopoietic cell proliferation. IL-4 stimulation of the IGF-IR transfectants resulted in enhanced tyrosine phosphorylation of SHC, Erk2, and signal transducer and activator of transcription 6 (STAT6) proteins. Both IL-4 and IGF-I were able to induce c-myc early response gene expression, and this expression was maximal in the presence of both factors. Finally, we demonstrated that a MAPK kinase inhibitor was able to suppress mitogenesis of the IGF-IR transfectants in response to IGF-I and/or IL-4. Together, our results suggest that IL-4 synergizes with IGF-I for hematopoietic cell proliferation, likely through cross talk between SHC/Grb2/MAPK and STAT6 pathways and through c-myc gene up-regulation. C1 NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. NIDR, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA. CUNY Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA. Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. RP Li, WQ (reprint author), NCI, Cellular & Mol Biol Lab, Bldg 37,Room 1E24,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009 NR 52 TC 45 Z9 45 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 MAY PY 1999 VL 19 IS 5 BP 3816 EP 3828 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 188AJ UT WOS:000079821100058 PM 10207105 ER PT J AU Ellinger-Ziegelbauer, H Kelly, K Siebenlist, U AF Ellinger-Ziegelbauer, H Kelly, K Siebenlist, U TI Cell cycle arrest and reversion of Ras-induced transformation by a conditionally activated form of mitogen-activated protein kinase kinase kinase 3 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GROWTH-FACTORS; S-PHASE; HUMAN FIBROBLASTS; MAMMALIAN-CELLS; NUCLEAR-PROTEIN; G(1) PHASE; 3T3 CELLS; D1; DIFFERENTIATION; PROLIFERATION AB Signal-induced proliferation, differentiation, or stress responses of cells depend on mitogen-activated protein kinase (MAPK) cascades, the core modules of which consist of members of three successively acting kinase families (MAPK kinase kinase [MAP3K], MAPK kinase, and MAPK). It is demonstrated here that the MEKK3 kinase inhibits cell proliferation, a biologic response not commonly associated with members of the MAP3K family of kinases. A conditionally activated form of MEKK3 stably expressed in fibroblasts arrests these cells in early G(1). MEKK3 critically blocks mitogen-driven expression of cyclin D1, a cyclin which is essential for progression of fibroblasts through G(1). The MEKK3-induced block of cyclin D1 expression and of cell cycle progression may be mediated via p38 MAPK, a downstream effector of MEKK3. The MEKK3-mediated block of proliferation also reverses Ras-induced cellular transformation, suggesting possible tumor-suppressing functions for this kinase. Together, these results suggest an involvement of the MEKK3 kinase in negative regulation of cell cycle progression, and they provide the first insights into biologic activities of this kinase. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Siebenlist, U (reprint author), NIAID, Immunoregulat Lab, NIH, 10 Ctr Dr MSC 1876,Bldg 10,Rm 11B-16, Bethesda, MD 20892 USA. NR 61 TC 67 Z9 71 U1 1 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 MAY PY 1999 VL 19 IS 5 BP 3857 EP 3868 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 188AJ UT WOS:000079821100062 PM 10207109 ER PT J AU Hoelzel, AR Stephens, JC O'Brien, SJ AF Hoelzel, AR Stephens, JC O'Brien, SJ TI Molecular genetic diversity and evolution at the MHC DQB locus in four species of pinnipeds SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE class II MHC; DQB; pinnipeds; molecular evolution ID MAJOR HISTOCOMPATIBILITY COMPLEX; ELEPHANT SEAL; NUCLEOTIDE SUBSTITUTIONS; POLYMORPHISM; SELECTION; DNA; RECOMBINATION; POPULATIONS; OVERDOMINANT; INFECTION AB Variation was investigated at exon 2 (including part of the putative peptide-binding region) of the class II major histocompatibility complex (MHC) DQB locus for two congeneric phocid seal species and two congeneric otariid seal species. Polymorphism in one phocid species, the southern elephant seal (Mirounga leonina), was comparable to that seen in human populations, while the other phocid, the northern elephant seal (Mirounga angustirostris), has been through a severe population bottleneck and exhibited much less variation at this locus. A phylogenetic comparison of the four species was consistent with the trans-specific pattern of evolution described for other taxa at this locus, and relative nonsynonymous and synonymous substitution rates suggest the maintenance of polymorphisms by natural selection. A comparison of sequence patterns also suggested that some variation could have been generated through recombinational events, primarily within genera. These results suggest a pattern of evolution of the immune response in pinnipeds similar to that in terrestrial mammal species. C1 Univ Durham, Dept Biol Sci, Durham DH1 3LE, England. Natl Canc Inst, Lab Genom Divers, Frederick, MD USA. RP Hoelzel, AR (reprint author), Univ Durham, Dept Biol Sci, S Rd, Durham DH1 3LE, England. NR 47 TC 68 Z9 80 U1 0 U2 14 PU SOC MOLECULAR BIOLOGY EVOLUTION PI LAWRENCE PA PO BOX 1897, LAWRENCE, KS 66044-8897 USA SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD MAY PY 1999 VL 16 IS 5 BP 611 EP 618 PG 8 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 194RX UT WOS:000080208300004 PM 10335654 ER PT J AU Clow, PA McNally, JG AF Clow, PA McNally, JG TI In vivo observations of myosin II dynamics support a role in rear retraction SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID OPTICAL-SECTIONING MICROSCOPY; REGULATORY LIGHT-CHAIN; DICTYOSTELIUM-DISCOIDEUM; HEAVY-CHAIN; CELL MOTILITY; SIGNAL-TRANSDUCTION; MUSCLE MYOSIN; MUTANT-CELLS; IN-VIVO; MORPHOGENESIS AB To investigate myosin II function in cell movement within a cell mass, we imaged green fluorescent protein-myosin heavy chain (GFP-MHC) cells moving within the tight mound of Dictyostelium discoideum. In the posterior cortex of cells undergoing rotational motion around the center of the mound, GFP-MHC cyclically formed a "C," which converted to a spot as the cell retracted its rear. Consistent with an important role for myosin in rotation, cells failed to rotate when they lacked the myosin II heavy chain (MHC-) or when they contained predominantly monomeric myosin II (3xAsp). Ln cells lacking the myosin II regulatory light chain (RLC-), rotation was impaired and eventually ceased. These rotational defects reflect a mechanical problem in the 3xAsp and RLC- cells, because these mutants exhibited proper rotational guidance cues. MHC- cells exhibited disorganized and erratic rotational guidance cues, suggesting a requirement for the MHC in organizing these signals. However, the MHC- cells also exhibited mechanical defects in rotation, because they still moved aberrantly when seeded into wild-type mounds with proper rotational guidance cues. The mechanical defects in rotation may be mediated by the C-to-spot, because RLC- cells exhibited a defective C-to-spot, including a slower C-to-spot transition, consistent with this mutant's slower rotational velocity. C1 Washington Univ, Dept Biol, St Louis, MO 63130 USA. Washington Univ, Inst Biomed Comp, St Louis, MO 63130 USA. RP McNally, JG (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, 41 Lib Dr,MSC 5055, Bethesda, MD 20892 USA. FU NIGMS NIH HHS [GM-47330] NR 44 TC 53 Z9 53 U1 2 U2 6 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAY PY 1999 VL 10 IS 5 BP 1309 EP 1323 PG 15 WC Cell Biology SC Cell Biology GA 196QJ UT WOS:000080318800003 PM 10233146 ER PT J AU Andrei, C Dazzi, C Lotti, L Torrisi, MR Chimini, G Rubartelli, A AF Andrei, C Dazzi, C Lotti, L Torrisi, MR Chimini, G Rubartelli, A TI The secretory route of the leaderless protein interleukin 1 beta involves exocytosis of endolysosome-related vesicles SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID BINDING CASSETTE TRANSPORTER; CYTOPLASMIC GROUND SUBSTANCE; LYSOSOMAL-ENZYME SECRETION; HUMAN-MONOCYTES; BAFILOMYCIN A(1); CATHEPSIN-D; CELL-DEATH; ATP; MACROPHAGES; PATHWAY AB Interleukin 1 beta (IL-1 beta), a secretory protein lacking a signal peptide, does not follow the classical endoplasmic reticulum-to-Golgi pathway of secretion. Here we provide the evidence for a "leaderless" secretory route that uses regulated exocytosis of preterminal endocytic vesicles to transport cytosolic IL-1 beta out of the cell. Indeed, although most of the IL-1 beta precursor (proIL-1 beta) localizes in the cytosol of activated human monocytes, a fraction is contained within vesicles that cofractionate with late endosomes and early lysosomes on Percoll density gradients and display ultrastructural features and markers typical of these organelles. The observation of organelles positive for both IL-1 beta and the endolysosomal hydrolase cathepsin D or for both IL-1 beta and the lysosomal marker Lamp-1 further suggests that they belong to the preterminal endocytic compartment. In addition, similarly to lysosomal hydrolases, secretion of IL-1 beta is induced by acidotropic drugs. Treatment of monocytes with the sulfonylurea glibenclamide inhibits both IL-1 beta secretion and vesicular accumulation, suggesting that this drug prevents the translocation of proIL-1 beta from the cytosol into the vesicles. A high concentration of extracellular ATP and hypotonic medium increase secretion of IL-1 beta but deplete the vesicular proIL-1 beta content, indicating that exocytosis of proIL-1 beta-containing vesicles is regulated by ATP and osmotic conditions. C1 Natl Canc Inst, I-16132 Genoa, Italy. Natl Canc Inst Genova, Biotechnol Sect, Rome, Italy. Univ Rome La Sapienza, Dept Expt Med & Pathol, I-00167 Rome, Italy. Ist Ricovero & Cura Carattere Sci, Ist Dermatol San Gallicano, I-00100 Rome, Italy. Ctr Immunol Marseille Luminy, F-13288 Marseille, France. RP Andrei, C (reprint author), Natl Canc Inst, I-16132 Genoa, Italy. NR 55 TC 297 Z9 300 U1 2 U2 10 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAY PY 1999 VL 10 IS 5 BP 1463 EP 1475 PG 13 WC Cell Biology SC Cell Biology GA 196QJ UT WOS:000080318800013 PM 10233156 ER PT J AU Zhou, Y Kato, H Shan, D Minami, R Kitazawa, S Matsuda, T Arima, T Barrett, JC Wake, N AF Zhou, Y Kato, H Shan, D Minami, R Kitazawa, S Matsuda, T Arima, T Barrett, JC Wake, N TI Involvement of mutations in the DPC4 promoter in endometrial carcinoma development SO MOLECULAR CARCINOGENESIS LA English DT Article DE 18q loss of heterozygosity; loss of DPC4 transcription; c/EBP beta; GATA-2 ID TUMOR-SUPPRESSOR GENE; TRANSCRIPTION FACTOR; ERYTHROID-DIFFERENTIATION; COLORECTAL CANCERS; BINDING-SITE; IN-VIVO; EXPRESSION; IDENTIFICATION; ADENOCARCINOMA; PROTEINS AB To define the target of chromosome 18q loss of heterozygosity, which is prevalent in endometrial carcinomas, we made a deletion map from 64 tumors. Loss of heterozygosity on 18q was found in 20 tumors. Among these, 14 tumors carried deletions at the 18q21.1 region, where the DPC4 gene is located. DPC4 transcription was disturbed in all six of the tumors with deletions at 18q21.1 examined, which sharply contrasted with the positive transcription in 12 tumors that retained heterozygosity at the 18q21.1 region. However, in the 14 tumors with the 18q21.1 deletions, the remaining allele had the wild-type sequence of the DPC4 coding region instead of somatic mutations in the DPC4 coding region. We found a one- and two-base substitutions in the DPC4 promoter in two of the six tumors that showed disturbed DPC4 transcription. Chloramphenicol acetyltransferase assays clearly demonstrated that the mutant promoters had the potential to suppress or silence DPC4 transcription, implicating the DPC4 gene in endometrial carcinoma. (C) 1999 Wiley-Liss, Inc. C1 Kyushu Univ, Med Inst Bioregulat, Dept Reprod Physiol & Endocrinol, Beppu, Oita 8740838, Japan. Kobe Univ, Sch Med, Dept Pathol 2, Kobe, Hyogo 650, Japan. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Wake, N (reprint author), Kyushu Univ, Med Inst Bioregulat, Dept Reprod Physiol & Endocrinol, 4546 Tsurumihara, Beppu, Oita 8740838, Japan. RI U-ID, Kyushu/C-5291-2016 NR 39 TC 20 Z9 24 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 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD MAY PY 1999 VL 25 IS 1 BP 64 EP 72 DI 10.1002/(SICI)1098-2744(199905)25:1<64::AID-MC8>3.0.CO;2-Z PG 9 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 193FT UT WOS:000080125800008 PM 10331746 ER PT J AU Walker, LC Marini, JC Grange, DK Filie, J Yeowell, HN AF Walker, LC Marini, JC Grange, DK Filie, J Yeowell, HN TI A patient with Ehlers-Danlos syndrome type VI is homozygous for a premature termination codon in exon 14 of the lysyl hydroxylase 1 gene SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Ehlers-Danlos syndrome type VI; lysyl hydroxylase deficiency; collagen hydroxylation; homozygosity; autosomal recessive disorder ID HUMAN-SKIN FIBROBLASTS; SPLICE-SITE MUTATION; MESSENGER-RNA LEVELS; 2 SIBLINGS; EPIDERMOLYSIS-BULLOSA; COMPOUND HETEROZYGOTE; NONSENSE MUTATIONS; HISTIDINE-RESIDUES; 7 EXONS; COLLAGEN AB In the present study, we have characterized a patient with Ehlers-Danlos syndrome type VI (EDS VI) as homozygous for a pathogenetic mutation in the lysyl hydroxylase 1 (LH1) gene. This mutant allele contributes to very low levels of LH1 mRNA and severely diminished LH activity in his skin fibroblasts. The reduced hydroxylysine content of collagen was reflected in the increased electrophoretic mobility of the type I collagen alpha 1 and alpha 2 chains precipitated from cell and media samples of cultured patient fibroblasts. The homozygous mutation, a single base change of C-1557 --> G which would convert a codon for tyrosine (TAC) at residue 511 to a stop codon (TAG) in exon 14 of the LH1 gene, was identified in full-length cDNAs for LH1 amplified from the patient's fibroblasts. We have demonstrated that the low level of LH activity measured in his fibroblasts may result from a minor processing pathway in which an in-frame skipping of exon 14 containing the mutation restores partial function of the enzyme. The mutation was confirmed in both alleles in genomic DNA from the proband and by the maternal inheritance of this mutation. The father's DNA was unavailable for analysis. The autosomal recessive nature of EDS VI was verified by the fact that the mother, who has one mutated and one normal allele, is clinically unaffected by this disorder. This mutation, which has been previously observed in another unrelated compound heterozygous patient, may prove to be a more widespread mutation for EDS VI. (C) 1999 Academic Press. C1 Duke Univ, Med Ctr, Durham, NC 27710 USA. NICHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. St Louis Univ, Sch Med, St Louis, MO 63104 USA. RP Yeowell, HN (reprint author), Duke Univ, Med Ctr, Box 3135, Durham, NC 27710 USA. FU NIA NIH HHS [AG10215]; NIAMS NIH HHS [AR17128] NR 51 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAY PY 1999 VL 67 IS 1 BP 74 EP 82 DI 10.1006/mgme.1999.2824 PG 9 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 198RE UT WOS:000080437100010 PM 10329027 ER PT J AU McCluskie, MJ Millan, CLB Gramzinski, RA Robinson, HL Santoro, JC Fuller, JT Widera, G Haynes, JR Purcell, RH Davis, HL AF McCluskie, MJ Millan, CLB Gramzinski, RA Robinson, HL Santoro, JC Fuller, JT Widera, G Haynes, JR Purcell, RH Davis, HL TI Route and method of delivery of DNA vaccine influence immune responses in mice and non-human primates SO MOLECULAR MEDICINE LA English DT Article ID B SURFACE-ANTIGEN; CYTOTOXIC T-LYMPHOCYTES; DIRECT GENE-TRANSFER; IMMUNODEFICIENCY-VIRUS TYPE-1; NUCLEIC-ACID IMMUNIZATION; IN-VIVO TRANSFECTION; MARROW-DERIVED CELLS; HERPES-SIMPLEX-VIRUS; PLASMID DNA; HEPATITIS-B AB Background: In spite of the large number of studies that have evaluated DNA-based immunization, few have directly compared the immune responses generated by different routes of immunization, particularly in non-human primates. Here we examine the ability of a hepatitis B surface antigen (HBsAg)-encoding plasmid to induce immune responses in mice and non-human primates (rhesus monkeys: Macaca mulatta) after delivery by a number of routes. Materials and Methods: Eight different injected [intraperitoneal (IP), intradermal (ID), intravenous (IV), intramuscular (IM), intraperineal (IPER), subcutaneous (SC), sublingual (SL), vaginal wall (VW)I and six noninjected [intranasal inhalation (WH), intranasal instillation (INS), intrarectal (IR), intravaginal (IVAG), ocular (Oc), oral feeding (oral)] routes and the gene gun (GG) were used to deliver HBsAg-expressing plasmid DNA to BALB/c mice. Sera were assessed for HBsAg-specific antibodies (anti-HBs, IgG, IgG1, IgG2a) and cytotoxic T lymphocyte (CTL) activity measured. Three of the most commonly used routes (LM, ID, GG) were compared in rhesus monkeys, also using HBsAg-expressing vectors. Monkeys were immunized with short (0-, 4- and 8-week) or long (0-, 12- and 24-week) intervals between boosts, and in the case of GG, also with different doses, and their sera were assessed for anti-HBs. Results: In one study, anti-HBs were detected in plasma of mice treated by five of eight of the injected and none of the six noninjected routes. The highest levels of anti-HBs were induced by IM and IV injections, although significant titers were also obtained with SL and ID. Each of these routes also induced CTL, as did IPER and VW and one noninjected route (INH) that failed to induce antibodies. In a second study, GG (1.6 mu g) was compared to ID and TM (100 mu g) delivery. Significant titers were obtained by all routes after only one boost, with the highest levels detected by IM. Delivery to the skin by GG induced exclusively IgG1 antibodies (Th2-like) at 4 weeks and only very low IgG2a levels at later times; ID-immunized mice bad predominantly IgG1 at 4 weeks and this changed to mixed IgG1/IgG2a over time. Responses with IM injection (in the leg or tongue) were predominantly IgG2a (Th1-like) at all times. IV injection gave mixed IgG1/IgG2a responses. In monkeys, in the first experiment, 1 mg DNA IM or ID at 0, 4, and 8 weeks gave equivalent anti-MB titers and 0.4 mu g at the same times by GG induced lower titers. In the second experiment, 1 mg DNA IM or ID, or 3.2 mu g by GG, at 0, 12, and 24 weeks, gave anti-MR values in the hierarchy of GG > IM > ID. Furthermore, high titers were retained after a single immunization in mice but fell off overtime in the monkeys, even after boost. Conclusions: Route of administration of plasmid DNA vaccines influences the strength and nature of immune responses in mice and non-human primates. However, the results in mice were not always predictive of those in monkeys and this is likely true for humans as well. Optimal dose and immunization schedule will most likely vary between species. It is not clear whether results in non-human primates will be predictive of results in humans, thus additional studies are required. C1 Ottawa Hosp, Loeb Hlth Res Inst, Ottawa, ON, Canada. Univ Ottawa, Fac Med, Dept Cellular & Mol Med, Ottawa, ON, Canada. USN, Med Res Inst, Malaria Program, Rockville, MD 20852 USA. Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA USA. PowerJect Vaccines, Madison, WI USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Ottawa, Fac Med, Dept Microbiol Immunol & Biochem, Ottawa, ON, Canada. Univ Ottawa, Sch Rehabil Sci, Fac Hlth Sci, Ottawa, ON, Canada. RP Davis, HL (reprint author), Loeb Hlth Res Inst, 725 Parkdale Ave, Ottawa, ON K1Y 4E9, Canada. FU NIAID NIH HHS [N01-AI-52705] NR 84 TC 132 Z9 140 U1 0 U2 12 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD MAY PY 1999 VL 5 IS 5 BP 287 EP 300 PG 14 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 217JB UT WOS:000081495300002 PM 10390545 ER PT J AU Schiller, JT AF Schiller, JT TI Papillomavirus-like particle vaccines for cervical cancer SO MOLECULAR MEDICINE TODAY LA English DT Review ID VIRUS-LIKE PARTICLES; COTTONTAIL RABBIT PAPILLOMAVIRUS; IN-VITRO; NEUTRALIZING ANTIBODIES; CAPSID PROTEIN; L1 PROTEIN; IMMUNIZATION; TYPE-16; INFECTION; MUCOSAL AB Most cervical cancers are now known to be caused by human papillomavirus (HPV) infections. This provides an opportunity to prevent a major cause of cancer deaths in women through vaccination. Subunit vaccines based upon non-infectious papillomavirus-like particles (VLPs) are attractive candidates to prevent infection by oncogenic HPVs, anal clinical trials are now underway in addition, the strongly immunogenic characteristics of VLPs raise the possibility that they could also serve as vehicles for inducing therapeutic responses against HPV-induced neoplasia and other diseases. C1 NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Schiller, JT (reprint author), NCI, Cellular Oncol Lab, Bldg 36,Rm 1D32, Bethesda, MD 20892 USA. NR 33 TC 57 Z9 69 U1 0 U2 1 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 MAY PY 1999 VL 5 IS 5 BP 209 EP 215 DI 10.1016/S1357-4310(99)01463-X PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 220CJ UT WOS:000081646700008 PM 10322313 ER PT J AU Licinio, J Prolo, P McCann, SM Wong, ML AF Licinio, J Prolo, P McCann, SM Wong, ML TI Brain iNOS: current understanding and clinical implications SO MOLECULAR MEDICINE TODAY LA English DT Review ID NITRIC-OXIDE SYNTHASE; CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; IL-1 RECEPTOR ANTAGONIST; RAT GLIAL-CELLS; GENE-EXPRESSION; MULTIPLE-SCLEROSIS; 1,25-DIHYDROXYVITAMIN D-3; CEREBRAL-ISCHEMIA; INDUCIBLE ISOFORM AB Nitric oxide (NO) is a unique informational substance first identified as the endothelium-derived relaxing factor. It is generated by NO synthases and plays a prominent role in controlling a variety of organ functions in the cardiovascular, immune, reproductive and nervous systems. Inducible nitric oxide synthase (iNOS) is not normally present in the brain in youth but it can be detected in the brain after inflammatory, infectious or ischemic damage, as well as in the normal, aging brain. Brain INOS seems to contribute to the pathophysiology of many diseases that involve the central nervous system, but the role of iNOS appears to go beyond tissue damage. Brain iNOS might be required for adequate repair following injury or damage. The effects of brain iNOS on the balance between damage and repair make this enzyme a promising therapeutic target in human disease. C1 NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. RP Licinio, J (reprint author), NIMH, Clin Neuroendocrinol Branch, NIH, NIH Bldg 10-2D46,10 Ctr Dr MSC 1284, Bethesda, MD 20892 USA. RI Wong, Ma-Li/D-7903-2011; Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 FU NIMH NIH HHS [MH51583] NR 57 TC 89 Z9 92 U1 1 U2 2 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 MAY PY 1999 VL 5 IS 5 BP 225 EP 232 DI 10.1016/S1357-4310(99)01453-7 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 220CJ UT WOS:000081646700010 PM 10322315 ER PT J AU Palsson, B Thorgeirsson, S AF Palsson, B Thorgeirsson, S TI Decoding developments in Iceland SO NATURE BIOTECHNOLOGY LA English DT Editorial Material C1 Univ Calif San Diego, La Jolla, CA 92093 USA. NCI, Bethesda, MD 20892 USA. RP Palsson, B (reprint author), Univ Calif San Diego, La Jolla, CA 92093 USA. NR 5 TC 9 Z9 10 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAY PY 1999 VL 17 IS 5 BP 407 EP 407 DI 10.1038/8532 PG 1 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 192JE UT WOS:000080074500004 PM 10331779 ER PT J AU Rybak, SM AF Rybak, SM TI Uncloaking RNases SO NATURE BIOTECHNOLOGY LA English DT Letter ID CYTOTOXICITY C1 NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Rybak, SM (reprint author), NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAY PY 1999 VL 17 IS 5 BP 408 EP 408 DI 10.1038/8535 PG 1 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 192JE UT WOS:000080074500007 PM 10331782 ER PT J AU Xu, XL Wagner, KU Larson, D Weaver, Z Li, CL Ried, T Hennighausen, L Wynshaw-Boris, A Deng, CX AF Xu, XL Wagner, KU Larson, D Weaver, Z Li, CL Ried, T Hennighausen, L Wynshaw-Boris, A Deng, CX TI Conditional mutation of Brca1 in mammary epithelial cells results in blunted ductal morphogenesis and tumour formation SO NATURE GENETICS LA English DT Article ID SUSCEPTIBILITY GENE BRCA1; BREAST-CANCER; MOUSE; P53; EXPRESSION; MICE; RAD51; DIFFERENTIATION; LOCALIZATION; HOMOLOG AB Cre-mediated excision of exon 11 of the breast-tumour suppressor gene Brca1 in mouse mammary epithelial cells causes increased apoptosis and abnormal ductal development Mammary tumour formation occurs after long latency and is associated with genetic instability characterized by aneuploidy, chromosomal rearrangements or alteration of Trp53 (encoding p53) transcription. To directly test the role of p53 in Brca1-associated tumorigenesis, we introduced a Trp53-null allele into mice with mammary epithelium-specific inactivation of Brca1. The loss of p53 accelerated the formation of mammary tumours in these females. Our results demonstrate that disruption of Brca1 causes genetic instability and triggers further alterations, including the inactivation of p53, that lead to tumour formation. C1 NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. NCI, Dept Genet, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Deng, CX (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, 10-9N105, Bethesda, MD 20892 USA. RI Wagner, Kay-Uwe/B-6044-2009; deng, chuxia/N-6713-2016 NR 44 TC 494 Z9 506 U1 2 U2 12 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 MAY PY 1999 VL 22 IS 1 BP 37 EP 43 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 192TU UT WOS:000080096300020 PM 10319859 ER PT J AU Miettinen, PJ Chin, JR Shum, L Slavkin, HC Shuler, CF Derynck, R Werb, Z AF Miettinen, PJ Chin, JR Shum, L Slavkin, HC Shuler, CF Derynck, R Werb, Z TI Epidermal growth factor receptor function is necessary for normal craniofacial development and palate closure SO NATURE GENETICS LA English DT Article ID FACTOR-ALPHA-GENE; CLEFT-PALATE; EGF RECEPTOR; MICE LACKING; ORGAN-CULTURE; MOUSE; LIP; ASSOCIATION; DEFECTS; MORPHOGENESIS AB Craniofacial malformations are among the most frequent congenital birth defects in humans; cleft palate, that is inadequate fusion of the palatal shelves, occurs with an annual incidence of 1 in 700 to 1 in 1,000 live births among individuals of European descent(1). The secondary palate arises as bilateral outgrowths from the maxillary processes(2), and its formation depends on the coordinated development of craniofacial structures including the Meckel's cartilage and the mandible(3). Cleft lip and palate syndromes in humans are associated with polymorphisms in the gene (TGFA) encoding transforming growth factor-alpha (TGF-alpha), an epidermal growth factor receptor (EGFR) ligand made by most epithelia(1,4). Here we have characterized craniofacial develop ment in Egfr-deficient (Egfr(-/-)) mice. Newborn Egfr(-/-) mice have facial mediolateral defects including narrow, elongated snouts, underdeveloped lower jaw and a high incidence of cleft palate. Palatal shelf explants from Egfr(-/-) mice fused, but frequently had residual epithelium in the midline. In addition, morphogenesis of Meckel's cartilage was deficient in cultured mandibular processes from Egfr(-/-) embryos. The secretion of matrix metalloproteinases (MMPs) was diminished in Egfr(-/-) explants, consistent with the ability of EGF to increase MMP secretion and with the decreased MMP expression caused by inhibition of Egfr sig nailing in wild-type explants. Accordingly, inactivation of MMPs in wild-type explants phenocopied the defective morphology of Meckel's cartilage seen in Egfr(-/-) explants. Our results indicate that EGFR signalling is necessary for normal craniofacial development and that its role is mediated in part by its downstream targets, the MMPs, and may explain the genetic correlation of human cleft palate with polymorphisms in TGFA. C1 Univ Calif San Francisco, Dept Growth & Dev, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Cell Biol Program, San Francisco, CA 94143 USA. Univ Calif San Francisco, Program Dev Biol, San Francisco, CA 94143 USA. NIAMSD, Craniofacial Dev Sect, NIH, Bethesda, MD 20892 USA. Univ So Calif, Ctr Craniofacial Mol Biol, Los Angeles, CA 90025 USA. RP Miettinen, PJ (reprint author), Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland. FU NCI NIH HHS [CA54826]; NIAMS NIH HHS [AR41114]; NIDCR NIH HHS [DE10306] NR 28 TC 173 Z9 184 U1 1 U2 8 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 MAY PY 1999 VL 22 IS 1 BP 69 EP 73 DI 10.1038/8773 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 192TU UT WOS:000080096300025 PM 10319864 ER PT J AU Kitao, S Shimamoto, A Goto, M Miller, RW Smithson, WA Lindor, NM Furuichi, Y AF Kitao, S Shimamoto, A Goto, M Miller, RW Smithson, WA Lindor, NM Furuichi, Y TI Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndrome SO NATURE GENETICS LA English DT Article ID WERNERS-SYNDROME GENES; MOLECULAR-CLONING; BLOOMS-SYNDROME; IN-VIVO; INSTABILITY; HELICASE; HOMOLOG; SGS1; INTERACTS; MOSAICISM AB Rothmund-Thomson syndrome (RTS; also known as poikiloderma congenitale) is a rare, autosomal recessive genetic disorder characterized by abnormalities in skin and skeleton, juvenile cataracts, premature ageing and a predisposition to neoplasia(1-4). Cytogenetic studies indicate that cells from affected patients show genomic instability often associated with chromosomal rearrangements causing an acquired somatic mosaicism(5-9). The gene(s) responsible for RTS remains unknown. The genes responsible for Werner(10) and Bloom(11) syndromes (WRN and BLM, respectively) have been identified as homologues of Escherichia coli RecQ, which encodes a DNA helicase(12) that unwinds double-stranded DNA into single-stranded DNAs. Other eukaryotic homologues thus far identified are human RECQL (refs 13,14), Saccharomyces cerevisiae SGS1 (refs 15,16) and Schizosaccharomyces pombe rqh1(+) (ref, 17). We recently cloned two new human helicase genes, RECQL4 at 8q24.3 and RECQL5 at 17q25, which encode members of the RecQ helicase family(18), Here, we report that three RTS patients carried two types of compound heterozygous mutations in RECQL4, The fact that the mutated alleles were inherited from the parents in one affected family and were not found in ethnically matched controls suggests that mutation of RECQL4 at human chromosome 8q24.3 is responsible for at least some cases of RTS. C1 AGENE Res Inst, Kamakura, Kanagawa 2470063, Japan. Tokyo Metropolitan Otsuka Hosp, Toshima Ku, Tokyo 1700005, Japan. NCI, Bethesda, MD 20892 USA. Mayo Clin, Rochester, MN USA. RP Furuichi, Y (reprint author), AGENE Res Inst, Kamakura, Kanagawa 2470063, Japan. NR 19 TC 442 Z9 450 U1 0 U2 5 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 MAY PY 1999 VL 22 IS 1 BP 82 EP 84 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 192TU UT WOS:000080096300028 PM 10319867 ER PT J AU Marini, JC AF Marini, JC TI Osteogenesis imperfecta calls for caution SO NATURE MEDICINE LA English DT Letter C1 NICHHD, Heritable Disorders Branch, Bethesda, MD 20892 USA. RP Marini, JC (reprint author), NICHHD, Heritable Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 11 Z9 11 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 1999 VL 5 IS 5 BP 466 EP 466 DI 10.1038/8326 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 217KA UT WOS:000081497400002 PM 10229207 ER PT J AU Qiu, JM Mizukami, H Brown, KE AF Qiu, JM Mizukami, H Brown, KE TI Adeno-associated virus 2 co-receptors? SO NATURE MEDICINE LA English DT Letter C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Jichi Med Sch, Div Genet Therapeut, Ctr Mol Med, Minamikawachi, Tochigi 3290498, Japan. RP Qiu, JM (reprint author), NHLBI, Hematol Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Mizukami, Hiroaki/D-7674-2013 OI Mizukami, Hiroaki/0000-0001-8954-874X NR 0 TC 16 Z9 16 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 1999 VL 5 IS 5 BP 467 EP 467 DI 10.1038/8328 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 217KA UT WOS:000081497400005 PM 10229209 ER PT J AU Hirsch, VM AF Hirsch, VM TI Evolution of the fittest ends in tragedy SO NATURE MEDICINE LA English DT Editorial Material ID SIMIAN IMMUNODEFICIENCY VIRUS; MACAQUES; PLASMA C1 NIAID, Mol Microbiol Lab, Twinbrook Facil 2, Rockville, MD 20852 USA. RP Hirsch, VM (reprint author), NIAID, Mol Microbiol Lab, Twinbrook Facil 2, 12441 Parklawn Dr, Rockville, MD 20852 USA. NR 12 TC 5 Z9 5 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 1999 VL 5 IS 5 BP 488 EP 489 DI 10.1038/8369 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 217KA UT WOS:000081497400024 PM 10229221 ER PT J AU Finzi, D Blankson, J Siliciano, JD Margolick, JB Chadwick, K Pierson, T Smith, K Lisziewicz, J Lori, F Flexner, C Quinn, TC Chaisson, RE Rosenberg, E Walker, B Gange, S Gallant, J Siliciano, RF AF Finzi, D Blankson, J Siliciano, JD Margolick, JB Chadwick, K Pierson, T Smith, K Lisziewicz, J Lori, F Flexner, C Quinn, TC Chaisson, RE Rosenberg, E Walker, B Gange, S Gallant, J Siliciano, RF TI Latent infection of CD4(+) T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy SO NATURE MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; PERIPHERAL-BLOOD; LYMPH-NODES; IN-VIVO; LYMPHOCYTES; EXPRESSION; RESERVOIR; PLASMA; INDIVIDUALS AB Combination therapy for HIV-1 infection can reduce plasma virus to undetectable levels, indicating that prolonged treatment might eradicate the infection. However, HIV-1 can persist in a latent form in resting CD4(+) T cells. We measured the decay rate of this latent reservoir in 34 treated adults whose plasma virus levels were undetectable. The mean half-life of the latent reservoir was very long (43.9 months). If the latent reservoir consists of only 1 x 10(5) cells, eradication could take as long as 60 years. Thus, latent infection of resting CD4(+) T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective anti-retroviral therapy. C1 Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Cornell Univ, Coll Med, Dept Med, New York, NY 10021 USA. Georgetown Univ, Washington, DC 20007 USA. RIGHT, Washington, DC 20007 USA. NIAID, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charleston, MA 02129 USA. Massachusetts Gen Hosp, Div Infect Dis, Charleston, MA 02129 USA. Harvard Univ, Sch Med, Charleston, MA 02129 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. RP Siliciano, RF (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. RI Quinn, Thomas/A-2494-2010; OI Gange, Stephen/0000-0001-7842-512X FU NIAID NIH HHS [AI43222] NR 40 TC 1167 Z9 1190 U1 5 U2 44 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 1999 VL 5 IS 5 BP 512 EP 517 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 217KA UT WOS:000081497400031 PM 10229227 ER PT J AU Pitcher, CJ Quittner, C Peterson, DM Connors, M Koup, RA Maino, VC Picker, LJ AF Pitcher, CJ Quittner, C Peterson, DM Connors, M Koup, RA Maino, VC Picker, LJ TI HIV-1-specific CD4(+) T cells are detectable in most individuals with active HIV-1 infection, but decline with prolonged viral suppression SO NATURE MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL THERAPY; BONE-MARROW; RESPONSES; LYMPHOCYTES; RECONSTITUTION; ACTIVATION; MICE; TRANSPLANTATION; CYTOMEGALOVIRUS AB The role of HIV-1-specific CD4(+) T-cell responses in controlling HIV-1 infection remains unclear. Previous work has suggested that such cells are eliminated in the early stages of infection in most subjects, and thus cannot substantially contribute to host defense against HIV-l. Here, using flow cytometric detection of antigen-induced intracellular cytokines, we show that significant frequencies of gag specific, T-helper-l CD4(+) memory T cells are detectable in most subjects with active/progressive HIV-1 infection (median frequency, 0.12% of memory subset; range, 0-0.66%). Median frequencies of these cells were considerably higher in nonprogressive HIV-1 disease (0.40%), but there was substantial overlap between the two groups (range of nonprogressors, 0.10-1.7%). Continuous HIV-1 suppression with anti-retroviral therapy was associated with a time-dependent reduction in median frequencies of gag-specific CD4(+) memory T cells: 0.08% in subjects treated for 4-24 weeks, and 0.03% in subjects treated for 47-112 weeks. Thus, functional HIV-1-specific CD4(+) T cells are commonly available for support of anti-HIV-l effector responses in active disease, but their decline with anti-retroviral therapy indicates that immunologic participation in long-term HIV-1 control will probably require effective vaccination strategies. C1 Univ Texas, SW Med Ctr, Dept Pathol, Div Hematopathol & Immunol, Dallas, TX 75235 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Div Gen Internal Med, Dallas, TX 75235 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Div Infect Dis, Dallas, TX 75235 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Becton Dickinson Immunocytometry Syst, San Jose, CA 95131 USA. RP Pitcher, CJ (reprint author), Univ Texas, SW Med Ctr, Dept Pathol, Div Hematopathol & Immunol, Dallas, TX 75235 USA. FU NIAID NIH HHS [AI31545, AI35522] NR 34 TC 613 Z9 622 U1 2 U2 6 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 1999 VL 5 IS 5 BP 518 EP 525 DI 10.1038/8400 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 217KA UT WOS:000081497400032 PM 10229228 ER PT J AU Robinson, HL Montefiori, DC Johnson, RP Manson, KH Kalish, ML Lifson, JD Rizvi, TA Lu, S Hu, SL Mazzara, GP Panicali, DL Herndon, JG Glickman, R Candido, MA Lydy, SL Wyand, MS McClure, HM AF Robinson, HL Montefiori, DC Johnson, RP Manson, KH Kalish, ML Lifson, JD Rizvi, TA Lu, S Hu, SL Mazzara, GP Panicali, DL Herndon, JG Glickman, R Candido, MA Lydy, SL Wyand, MS McClure, HM TI Neutralizing antibody-independent containment of immunodeficiency virus challenges by DNA priming and recombinant pox virus booster immunizations SO NATURE MEDICINE LA English DT Article ID T-LYMPHOCYTE RESPONSES; VACCINIA VIRUS; PROTECTIVE EFFICACY; ATTENUATED SIV; FOWLPOX VIRUS; HIV VACCINE; TYPE-1 ENV; INFECTION; CELLS; GENE AB Eight different protocols were compared for their ability to raise protection against immunodeficiency virus challenges in rhesus macaques. The most promising containment of challenge infections was achieved by intradermal DNA priming followed by recombinant fowl pox virus booster immunizations. This containment did not require neutralizing antibody and was active for a series of challenges ending with a highly virulent virus with a primary isolate envelope heterologous to the immunizing strain. C1 Yerkes Reg Primate Res Ctr, Atlanta, GA 30329 USA. Duke Univ, Med Ctr, Durham, NC 27710 USA. New England Reg Primate Res Ctr, Southborough, MA 01772 USA. Harvard Univ, Sch Med, AIDS Res Ctr, Southborough, MA 01772 USA. GTC Mason Labs, Worcester, MA 01608 USA. Ctr Dis Control, Atlanta, GA 30333 USA. NCI, Frederick Canc Res Ctr, Frederick, MD 21702 USA. Univ Texas, MD Anderson Canc Ctr, Bastrop, TX 78802 USA. Univ Massachusetts, Med Ctr, Div Infect Dis, Worcester, MA 01655 USA. Univ Washington, Reg Primate Res Ctr, Seattle, WA 98195 USA. Therion Biol, Cambridge, MA 02142 USA. RP Robinson, HL (reprint author), Yerkes Reg Primate Res Ctr, Atlanta, GA 30329 USA. RI Hu, Shiu-Lok/A-3196-2008 OI Hu, Shiu-Lok/0000-0003-4336-7964 FU NIAID NIH HHS [P01-AI-43045, R01-AI-34241, R01-AI-40334] NR 49 TC 335 Z9 337 U1 0 U2 6 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 1999 VL 5 IS 5 BP 526 EP 534 DI 10.1038/8406 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 217KA UT WOS:000081497400033 PM 10229229 ER PT J AU Lacana', E D'Adamio, L AF Lacana', E D'Adamio, L TI Regulation of Fas ligand expression and cell death by apoptosis-linked gene 4 SO NATURE MEDICINE LA English DT Article ID NF-KAPPA-B; LYMPHOPROLIFERATIVE SYNDROME; POLY(ADP-RIBOSE) POLYMERASE; LYMPHOCYTE APOPTOSIS; CLONAL ELIMINATION; SIGNALING COMPLEX; IMMUNE EVASION; T-LYMPHOCYTES; CD95 LIGAND; ACTIVATION AB Programmed cell death is a process required for the normal development of an organism. One of the best understood apoptotic pathways occurs in T lymphocytes and is mediated by Fas/Fas ligand (FasL) interaction. During studies of apoptosis induced by T cell-receptor engagement, we identified ALG-4F, a truncated transcript that prevents T cell-receptor-induced FasL upregulation and cell death. Overexpression of full-length ALG-4 induced transcription of Fast and, consequently, apoptosis. These results indicate that ALG-4 is necessary and sufficient for Fast expression. Fas/FasL interaction initiates cell death in many other systems, and its dysregulation is a mechanism by which several pathologic conditions arise. Understanding the molecular mechanisms of Fast regulation could be very useful in elucidating how these diseases develop and in identifying potential therapeutic targets. C1 NIAID, Cellular & Mol Immunol Lab, T Cell Apoptosis Unit, NIH, Bethesda, MD 20892 USA. RP D'Adamio, L (reprint author), NIAID, Cellular & Mol Immunol Lab, T Cell Apoptosis Unit, NIH, 9000 Rockville Pike,Bldg 4,Rm 111, Bethesda, MD 20892 USA. FU Fondazione Telethon NR 46 TC 14 Z9 15 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 1999 VL 5 IS 5 BP 542 EP 547 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 217KA UT WOS:000081497400035 PM 10229231 ER PT J AU von Kugelgen, I Norenberg, W Meyer, A Illes, P Starke, K AF von Kugelgen, I Norenberg, W Meyer, A Illes, P Starke, K TI Role of action potentials and calcium influx in ATP- and UDP-induced noradrenaline release from rat cultured sympathetic neurones SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Article DE rat sympathetic neurones; P2X-receptor; uracil nucleotide receptor; alpha(2)-adrenoceptor; action potential; calcium influx; noradrenaline release ID GATED ION CHANNELS; TRANSMITTER RELEASE; GUINEA-PIG; NUCLEOTIDE RECEPTORS; GANGLION-CELLS; CELIAC NEURONS; VAS-DEFERENS; PATCH-CLAMP; INHIBITION; PURINOCEPTORS AB Adenine and uracil nucleotides release noradrenaline from rat postganglionic sympathetic neurones by activation of P2X-receptors and distinct receptors for uracil nucleotides, respectively. The present study on cultured neurones of rat thoracolumbal paravertebral ganglia has analysed the involvement of action potentials and calcium influx in the nucleotide-induced transmitter release. ATP and UDP (100 mu M each) caused a marked release of previously incorporated [H-3]noradrenaline. The P2-receptor antagonists suramin (300 mu M) and cibacron blue 3GA (3 mu M) decreased the ATP-induced but not the UDP-induced release. The response to ATP was decreased by the sodium channel blocker tetrodotoxin (0.5 mu M; by 47%), by the N-type calcium channel blocker omega-conotoxin GVIA (100 nM; by 35%), and by the alpha(2)-adrenoceptor agonist UK-14,304 (1 mu M by 45%); it was not changed by the potassium channel blocker tetraethylammonium (10 mM). The response to UDP was abolished by tetrodotoxin, greatly decreased by omega-conotoxin (by 78%), also abolished by UK-14,304, and increased by tetraethylammonium (by 410%). ATP (100 mu M) caused a marked increase in intraaxonal free calcium as measured by fura-2 microfluorimetry. Withdrawal of extracellular calcium diminished the calcium response to ATP by 85%, and tetrodotoxin and omega-conotoxin diminished it by about 40%. As studied with the amphotericin B-perforated patch method, ATP (100 mu M) induced a large depolarisation and action potential firing. UDP (100 mu M) induced only a small depolarisation but it also elicited action potentials. UDP increased the excitability of the neurones. The results indicate that the ATP-induced release of noradrenaline depends on influx of calcium from the extracellular space. Calcium passes through two structures: volt age-gated channels and - probably - the P2X-receptor itself. Only that component of ATP-induced transmitter release which is triggered by opening of voltage-gated calcium channels is sensitive to modulation by alpha(2)-adrenoceptors. In contrast to ATP, the UDP-induced release of noradrenaline is entirely due to generation of action potentials followed by calcium influx through voltage-gated channels. All of the UDP-induced release is therefore sensitive to alpha(2)-adrenoceptor modulation. C1 Univ Freiburg, Inst Pharmakol, D-79104 Freiburg, Germany. Univ Leipzig, Inst Pharmakol, D-04107 Leipzig, Germany. RP von Kugelgen, I (reprint author), NIDDK, NIH, Bldg 8A,Room B1-A23,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Norenberg, Wolfgang/A-1999-2008 OI Norenberg, Wolfgang/0000-0002-0086-3717 NR 54 TC 32 Z9 33 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD MAY PY 1999 VL 359 IS 5 BP 360 EP 369 DI 10.1007/PL00005362 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 201JW UT WOS:000080592500002 PM 10498285 ER PT J AU Stadtman, ER Levine, RL AF Stadtman, ER Levine, RL TI Oxidation of cellular proteins by beta-amyloid peptide SO NEUROBIOLOGY OF AGING LA English DT Editorial Material ID ALZHEIMERS-DISEASE; FREE-RADICALS; IN-VITRO; NEUROTOXICITY; TOXICITY; AGGREGATION C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Stadtman, ER (reprint author), NHLBI, Biochem Lab, NIH, Bldg 3,Room 222,3 Ctr Dr, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 25 TC 6 Z9 6 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAY-JUN PY 1999 VL 20 IS 3 BP 331 EP 333 PG 3 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 258DF UT WOS:000083822300010 PM 10588581 ER PT J AU Ferguson, JH AF Ferguson, JH TI Curative and population medicine: Bridging the great divide SO NEUROEPIDEMIOLOGY LA English DT Review DE curative medicine; population medicine; public health; screening; toxic torts; science in court; numeracy ID PUBLIC-HEALTH; CLINICAL-PRACTICE; SUPREME-COURT; INFORMATION; MAMMOGRAPHY; PHYSICIANS; CONSENSUS; CARE AB There are gaps in understanding between practicing physicians (curative medicine) and those trained in public health and epidemiology (population medicine). In the last century, these groups were closer, as physicians played a role in public health, sanitation and in the prevention of the spreading of infection. However, with the recent extraordinary successes of the biomedical model in explaining disease, and the ensuing explosion of remarkable - and expensive - medical procedures and treatments, public health, preventive medicine and the population approach in general have been overshadowed. In this essay, I try to explain how the training of physicians and the daily care of patients may hinder their appreciation of the population model. For instance, for many of the myriad decisions involved in patient care in daily practice, there is little evidence, population derived or otherwise. What little evidence there is may be dominated by personal experiences, opinions and values. Additionally, the statistical and epidemiologic approach necessary for the maintenance of health and prevention of illness may not be valued by practitioners whose training and focus is on treating sick people one by one. To illustrate these disparities in understanding, examples are given from the NIH Consensus Conference on mammography screening for women aged 40-49, and from the use of science in the courtroom in adjudicating toxic tort cases. Understanding population medicine requires an appreciation of the concepts of chance, probability and statistics and of epidemiologic principles, difficult areas for many - including the general public. These topics play a small to nonexistent role in the formal training of most physicians. Some closing of the gap in understanding may be occurring. It is hoped this essay will help. C1 NIH, Off Med Applicat Res, Bethesda, MD 20892 USA. RP Ferguson, JH (reprint author), NIH, Off Med Applicat Res, 31 Ctr Dr,MSC-2082, Bethesda, MD 20892 USA. EM jferg@helix.nih.gov NR 41 TC 3 Z9 3 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 EI 1423-0208 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PD MAY-JUN PY 1999 VL 18 IS 3 BP 111 EP 119 DI 10.1159/000026202 PG 9 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 188YQ UT WOS:000079877300001 PM 10202265 ER PT J AU Smith, AM Lewis, BK Ruttimann, UE Ye, FQ Sinnwell, TM Yang, YH Duyn, JH Frank, JA AF Smith, AM Lewis, BK Ruttimann, UE Ye, FQ Sinnwell, TM Yang, YH Duyn, JH Frank, JA TI Investigation of low frequency drift in fMRI signal SO NEUROIMAGE LA English DT Article DE functional magnetic resonance imaging (fMRI); low frequency drift; BOLD; artifacts ID ECHO-PLANAR MRI; FUNCTIONAL MRI; MOTOR CORTEX; HUMAN BRAIN; TIME; LESIONS; IMAGES; TISSUE AB Low frequency drift (0.0-0.015 Hz) has often been reported in time series fMRI data. This drift has often been attributed to physiological noise or subject motion, but no studies have been done to test this assumption. Time series T-2*-weighted volumes were acquired on two clinical 1.5 T MRI systems using spiral and EPI readout gradients from cadavers, a normal volunteer, and nonhomogeneous and homogeneous phantoms. The data were tested for significant differences (P = 0.001) from Gaussian noise in the frequency range 0.0-0.015 Hz. The percentage of voxels that were significant in data from the cadaver, normal volunteer, nonhomogeneous and homogeneous phantoms were 13.7-49.0%, 22.1-61.9%, 46.4-68.0%, and 1.10%, respectively. Low frequency drift was more pronounced in regions with high spatial intensity gradients. Significant drifting was present in data acquired from cadavers and nonhomogeneous phantoms and all pulse sequences tested, implying that scanner instabilities and not motion or physiological noise may be the major cause of the drift. (C) 1999 Academic Press. C1 NIMH, NIH, Bethesda, MD 20892 USA. NIAAA, Lab Diagnost Radiol Res, Bethesda, MD USA. RP Smith, AM (reprint author), Univ Catholique Louvain, Clin Univ St Luc, Brussels, Belgium. RI Duyn, Jozef/F-2483-2010 NR 23 TC 174 Z9 176 U1 1 U2 8 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY PY 1999 VL 9 IS 5 BP 526 EP 533 DI 10.1006/nimg.1999.0435 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 200KR UT WOS:000080539300008 PM 10329292 ER PT J AU Foo, TKF Ho, VB Choyke, PL AF Foo, TKF Ho, VB Choyke, PL TI Contrast-enhanced carotid MR angiography - Imaging principles and physics SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID MAGNETIC-RESONANCE ANGIOGRAPHY; BREATH-HOLD; ACQUISITION ORDER; TIME; ARTERIES; OPTIMIZATION; DISEASE; AORTOGRAPHY; SATURATION; EXCITATION C1 GE, Med Syst, Appl Sci Lab, Milwaukee, WI 53201 USA. Uniformed Serv Univ Hlth Sci, Dept Radiol, Bethesda, MD 20814 USA. NIH, Dept Radiol, Bethesda, MD 20892 USA. NR 41 TC 10 Z9 10 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 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD MAY PY 1999 VL 9 IS 2 BP 263 EP 284 PG 22 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 204VG UT WOS:000080784800005 PM 10318714 ER PT J AU Torpy, DJ Webster, EL Zachman, EK Aguilera, G Chrousos, GP AF Torpy, DJ Webster, EL Zachman, EK Aguilera, G Chrousos, GP TI Urocortin and inflammation: Confounding effects of hypotension on measures of inflammation SO NEUROIMMUNOMODULATION LA English DT Article DE urocortin; inflammation; blood pressure ID CORTICOTROPIN-RELEASING HORMONE; PEPTIDE; NEUROPEPTIDE; INJURY; RATS; CRF AB Urocortin, a newly isolated 40-amino-acid mammalian peptide homologous to corticotropin-releasing hormone (CRH), activates both CRH type 1 and 2 receptors, but may be an endogenous ligand for CRH receptor type 2. Urocortin given systemically inhibited heat-induced paw edema in the rat, and was therefore ascribed anti-inflammatory properties. We examined the effects of urocortin in the carrageenin-induced subcutaneous inflammation model. Rats were treated with urocortin 200 (n = 6) or 20 nmol/kg (n = 6); inflammatory exudates were reduced by approximately 30% compared to controls (n = 7) at both doses. However, since subcutaneous urocortin has been shown to reduce arterial blood pressure, we tested the hypothesis that its antiedema and antiextravasatory effects were secondary to arterial hypotension. Therefore, we examined the parallel effects of urocortin- and hydralazine-induced hypotension on acute inflammation induced by carrageenin in the rat. Rats were treated with subcutaneous carrageenin and control injections (n = 8), carrageenin and urocortin (20 nmol/kg, n = 9), or carrageenin and intraperitoneal hydralazine (10 mg/kg, n = 8). Mean arterial blood pressure was measured hourly for 7 h in 12 animals, and after 2 h, the nadir of treatment, in a further 13 animals. Rats were then sacrificed, and the inflammatory exudate volume and leukocyte count were measured. Mean exudate volumes were reduced from 4.8 +/- 0.5 ml (controls) to 2.4 +/- 0.3 ml (p = 0.004) and 2.9 +/- 0.6 ml (p = 0.007) in urocortin- and hydralazine-treated animals, respectively. Urocortin and hydralazine both produced a significant fall in blood pressure compared to controls, with mean arterial pressure 2 h after carrageenin injection falling to 51.0 +/- 4.1 (p < 0.001) and 34.6 +/- 4.6 (p < 0.001) vs. 92.9 +/- 3.7 mm Hg in controls, respectively. A significant positive correlation was noted between blood pressure and inflammatory exudate volume (r = 0.52, p = 0.007). As both hydralazine and urocortin lowered blood pressure and inflammatory exudate volume, we suggest that the anti-inflammatory effects of urocortin and related neuropeptides may be nonspecific, acting through hypotension rather than through direct antiinflammatory mechanisms. The use of inflammatory models which rely on extravasation may be inappropriate for the study of substances that produce hypotension. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Torpy, DJ (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10,Rom 10N262, Bethesda, MD 20892 USA. NR 16 TC 33 Z9 34 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PD MAY-JUN PY 1999 VL 6 IS 3 BP 182 EP 186 DI 10.1159/000026380 PG 5 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA 190PZ UT WOS:000079974300005 PM 10213916 ER PT J AU Nelson, KB AF Nelson, KB TI The neurologically impaired child and alleged malpractice at birth SO NEUROLOGIC CLINICS LA English DT Article ID FACTOR-V-LEIDEN; SPASTIC CEREBRAL-PALSY; WESTERN-AUSTRALIA; INFANTS; WEIGHT; ASPHYXIA; RISK; CHORIOAMNIONITIS; ERYTHROPOIETIN; ANTECEDENTS AB Some of the largest awards in medical litigation have been made for neurologic impairment in children. Neurologists are often asked to serve as expert witnesses in such cases, to testify concerning causation of the neurologic disability and to assist the court in estimating life expectancy. An especially common topic of contention has been the role of birth asphyxia in the cause of neurologic impairment. The group of congenital neurologic disorders called the Developmental Disabilities includes mental retardation (developmental cognitive disability), cerebral palsy (developmental motor disability), epilepsy, autism, and learning disabilities. The old hypothesis was that all these are commonly the results of birth asphyxia; that hypothesis has not been confirmed by studies over the past decade or two.(6,30,32) In fact, the majority of each of the Developmental Disabilities-even mental retardation for which a number of specific causes are now recognized-are still largely biologically unexplained Except when these disabilities occur in the same individual, each has a different spectrum of causes. This article focuses on recent evidence concerning the origin of cerebral palsy (CP), probably the most common topic of litigation concerning neurologically impaired infants; this article focuses especially on what is known of the cause of CP in term and near-term infants, who make up the enormous majority of all births. In the course of this century, there have been striking declines in maternal and in fetal and infant mortality and injuries, and there have also been declines in diagnosed birth asphyxia.(19) Physical trauma to the fetus during birth is now rare. Neonatal care has also improved drastically. These improvements in obstetric and neonatal care have not been followed by a net decline in the CP rate in any birthweight group, however(20,28,37,46); because of the improved survival of fragile premature or very ill infants, there has been some increase in CP. The observation that improved medical care has not led to less CP has been made repeatedly and in different populations. The occurrence of CP is not a good indicator of the quality of medical care in a population or in an individual. C1 NINDS, Neuroepidemiol Branch, Bethesda, MD 20892 USA. RP Nelson, KB (reprint author), 7550 Wisconsin Ave,Room 714, Bethesda, MD 20892 USA. NR 56 TC 16 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 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD MAY PY 1999 VL 17 IS 2 BP 283 EP + DI 10.1016/S0733-8619(05)70131-6 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 201QD UT WOS:000080605700008 PM 10196409 ER PT J AU Wassermann, EM Blaxton, TA Hoffman, EA Berry, CD Oletsky, H Pascual-Leone, A Theodore, WH AF Wassermann, EM Blaxton, TA Hoffman, EA Berry, CD Oletsky, H Pascual-Leone, A Theodore, WH TI Repetitive transcranial magnetic stimulation of the dominant hemisphere can disrupt visual naming in temporal lobe epilepsy patients SO NEUROPSYCHOLOGIA 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 DE language; brain mapping; frontal lobe; handedness; hemispheric dominance; reading ID SIMPLE REACTION-TIME; BRAIN-STIMULATION; SOMATOSENSORY STIMULI; LANGUAGE AREA; SPEECH; INDUCTION; HUMANS; SITE AB We used repetitive transcranial magnetic stimulation (rTMS) to study visual naming in 14 patients with temporal lobe epilepsy. Ten had left hemisphere language by Wada testing and all experienced speech arrest with rTMS of the motor speech area in the left frontal lobe. One left-hander had speech arrest with stimulation of sites on both sides. Subjects were asked to name pictures or read words presented on a computer monitor, rTMS was delivered on half of the trials. Stimulation sites were the motor speech area in the left frontal lobe, the mirror site on the right, and the left and right mid superior and posterior temporal lobes. rTMS at left hemisphere sites caused more naming errors than did right hemisphere rTMS. All individual subjects, except two who had temporal lobe resections and the one with bilateral speech arrest, produced more naming errors with rTMS of left hemisphere sites. There was no significant effect on word reading. rTMS at the left hemisphere and right frontal sites produced reductions in reaction time for picture naming, but not for word reading. This was observed for both correct and incorrect responses. This study shows that left hemisphere rTMS can disrupt visual naming selectively. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 NINDS, Off Clin Director, NIH, Bethesda, MD 20892 USA. NINDS, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA USA. RP Wassermann, EM (reprint author), NINDS, Off Clin Director, NIH, 10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA. NR 22 TC 66 Z9 66 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD MAY PY 1999 VL 37 IS 5 BP 537 EP 544 DI 10.1016/S0028-3932(98)00102-X PG 8 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 189KV UT WOS:000079904400003 PM 10340313 ER PT J AU Lee, SS Wild, K Hollnagel, C Grafman, J AF Lee, SS Wild, K Hollnagel, C Grafman, J TI Selective visual attention in patients with frontal lobe lesions or Parkinson's disease SO NEUROPSYCHOLOGIA LA English DT Article DE visual attention; frontal lobes; frontal lobe lesion; Parkinson's disease; flanker task ID POSITRON EMISSION TOMOGRAPHY; AGE-RELATED DIFFERENCES; PSYCHOPHYSIOLOGICAL ANALYSES; FUNCTIONAL-ANATOMY; PERFORMANCE; DYSFUNCTION; DEFICITS; TASK AB Visual selective attention and response competition were tested in patients with frontal lobe lesions or with Parkinson's disease, and matched normal controls. The target stimuli were presented with flanking distracters that were either compatible, incompatible, or neutral to the target stimulus. The distance between the target and distracters was systematically varied. A control condition without distracters was also included. Subjects' response times to target stimuli and accuracy were measured. Both patient groups responded significantly slower and less accurately than their respective matched normal controls across all interference conditions and spatial distances. However, they did not show significantly greater interference or facilitation effects. Thus, the data suggest that the cognitive processes underlying selective attention are, in general, spared in patients with frontal lobe lesions or basal ganglia dysfunction. Published by Elsevier Science Ltd. C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, 10 Ctr Dr,MSC 1440, Bethesda, MD 20892 USA. OI Grafman, Jordan H./0000-0001-8645-4457 NR 38 TC 31 Z9 31 U1 2 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD MAY PY 1999 VL 37 IS 5 BP 595 EP 604 DI 10.1016/S0028-3932(98)00081-5 PG 10 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 189KV UT WOS:000079904400008 PM 10340318 ER PT J AU Nielsen, DA Mazzanti, CM Linnoila, M Goldman, D AF Nielsen, DA Mazzanti, CM Linnoila, M Goldman, D TI Serotonin transporter and seasonal variation in serotonin function SO NEUROPSYCHOPHARMACOLOGY LA English DT Letter ID POLYMORPHISM C1 NIAAA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD USA. NIAAA, Clin Studies Lab, NIH, Bethesda, MD 20892 USA. RP Nielsen, DA (reprint author), Pk V,Room 451,12420 Parklawn Dr, Rockville, MD 20852 USA. RI Nielsen, David/B-4655-2009; Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 4 TC 4 Z9 4 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 MAY PY 1999 VL 20 IS 5 BP 507 EP 508 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 179UA UT WOS:000079346500011 PM 26468552 ER PT J AU Vance, CL Begg, CM Lee, WL Dubel, SJ Copeland, TD Sonnichsen, FD McEnery, MW AF Vance, CL Begg, CM Lee, WL Dubel, SJ Copeland, TD Sonnichsen, FD McEnery, MW TI N-type calcium channel/syntaxin/SNAP-25 complex probed by antibodies to II-III intracellular loop of the alpha(1B) subunit SO NEUROSCIENCE LA English DT Article DE anti-peptide antibodies; alpha(1B) subunit; syntaxin; SNAP-25; synprint site; SNARE complex ID PROTEIN SECONDARY STRUCTURE; CONOTOXIN GVIA RECEPTOR; CA2+ CHANNELS; NEUROTRANSMITTER RELEASE; FUNCTIONAL EXPRESSION; SYNAPTIC VESICLES; MOLECULAR-CLONING; INTERACTION SITE; SYNAPTOTAGMIN-I; ALPHA-1 SUBUNIT AB Neuronal voltage-dependent calcium channels are integral components of cellular excitation and neurosecretion. In addition to mediating the entry of calcium across the plasma membrane, both N-type and P/Q-type voltage-dependent calcium channels have been shown to form stable complexes with synaptic vesicle and presynaptic membrane proteins, indicating a structural role for the voltage-dependent calcium channels in secretion. Recently, detailed structural analyses of N-type calcium channels have identified residues amino acids 718-963 as the site in the rat alpha(1B) subunit that mediates binding to syntaxin, synaptosome-associated protein of 25,000 mol. wt and synaptotagmin [Sheng et al. (1996) Nature 379, 451-454]. The purpose of this study was to employ site-directed antibodies to target domains within and outside of the interaction site on the rat alpha(1B) to probe potential binding sites for syntaxin/SNAP-25/synaptotagmin. Our results demonstrate that both antibodies employed in this study have access to their epitopes on the alpha(1B) as evidenced by equivalent immunoprecipitation of native [I-125]omega-conotoxin GVIA-labeled alpha(1B) protein from CHAPS-solubilized preparations. The N-type voltage-dependent calcium channel immunoprecipitated by Ab CW14, the antibody directed to a domain outside of the synprint site, is associated with syntaxin and SNAP-25 with the recovery of these proteins, increasing in parallel to the recovery of alpha(1B). However, when we used the antibody raised to an epitope within the synprint site (Ab CW8) to immunoprecipitate N-type calcium channels, the alpha(1B) was depleted of more than 65% of syntaxin and 80% of SNAP-25 when compared to the recovery of these proteins using Ab CW14. This is the first report of a defined epitope on the alpha(1B) subunit II-III loop (amino acids 863-875) whose perturbation by a site-directed antibody influences the dissociation of SNAP-25 and syntaxin. (C) 1999 IBRO. Published by Elsevier Science Ltd. C1 Case Western Reserve Univ, Sch Med, Dept Physiol & Biophys, Cleveland, OH 44106 USA. NCI, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP McEnery, MW (reprint author), Case Western Reserve Univ, Sch Med, Dept Physiol & Biophys, 10900 Euclid Ave, Cleveland, OH 44106 USA. RI Sonnichsen, Frank/D-8408-2011 OI Sonnichsen, Frank/0000-0002-4539-3755 NR 45 TC 11 Z9 11 U1 0 U2 0 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 MAY PY 1999 VL 90 IS 2 BP 665 EP 676 DI 10.1016/S0306-4522(98)00420-5 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 178FM UT WOS:000079255600030 PM 10215168 ER PT J AU Levin, ED Simon, BB Schmechel, DE Glasgow, HB Deamer-Melia, NJ Burkholder, JM Moser, VC Jensen, K Harry, GJ AF Levin, ED Simon, BB Schmechel, DE Glasgow, HB Deamer-Melia, NJ Burkholder, JM Moser, VC Jensen, K Harry, GJ TI Pfiesteria toxin and learning performance SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the Society-of-Toxicology CY MAR 01-05, 1998 CL SEATTLE, WASHINGTON SP Soc Toxicol DE Pfiesteria piscicida; learning; radial-arm maze; activity; figure-8 maze ID FUNCTIONAL OBSERVATIONAL BATTERY; ESTUARINE DINOFLAGELLATE; PISCICIDA; EXPOSURE AB Pfiesteria piscicida is an estuarine dinoflagellate involved with fish kills along the east coast of the United States. We previously documented a radial-arm maze learning deficit in rats exposed to Pfiesteria that may be related to cognitive deficits seen in humans after accidental Pfiesteria exposure. The current study elucidated important behavioral parameters of this deficit. There were six dose groups. Forty (10/group) adult female Sprague-Dawley rats were injected (SC) with a single dose of Pfiesteria taken from aquarium-cultured Pfiesteria (35,600, 106,800, or 320,400 Pfiesteria cells/kg of rat body weight or a cell-free filtrate of the 106,800 cells/kg dose). One control group (N = 10) was injected with saline and one (N = 10) with aquarium water not containing Pfiesteria. Half of the rats in each group were tested on an 8-arm radial maze in a standard test room, and the other half were tested on the radial maze in a sound-attenuating chamber. In the standard maze room, there was a significant effect of Pfiesteria (p < 0.05) impairing choice accuracy improvement over the first six sessions of training among rats administered 106,800, 320,400, and the 106,800 cells/kg filtered sample. In contrast, there was no indication of an effect of Pfiesteria when the rats were tested-on the same configuration radial maze in the sound-attenuating chamber. After 18 sessions of training in one room, the rats were switched for six sessions of testing in the other room and finally were switched back to their original room for three sessions. There was a significant Pfiesteria-induced deficit when the rats were tested in the standard test room but not when they were tested in the sound-attenuating chamber. When the Pfiesteria-exposed rats were initially switched from the sound-attenuating chamber to the standard test room they performed significantly worse than controls, whereas Pfiesteria-treated rats switched from the standard test room to the sound-attenuating chamber did not perform differently from controls. These results suggest that the Pfiesteria-induced learning impairment may result from the negative impact of distracting stimuli. At the time of the learning impairment, no overt Pfiesteria-related effects were seen using a functional observational battery and no overall response latency effects were seen, indicating that the Pfiesteria-induced choice accuracy deficit was not due to generalized debilitation. In the initial use of the figure-8 maze in this line of research, the rats in the same Pfiesteria treatment groups that showed significant deficits in the radial-arm maze showed greater declines in activity rates in a 1-h figure-8 locomotor activity test. Both the 106,800 and 320,400 Pfiesteria cells/kg groups showed significantly greater linear trends of activity decline relative to tank water-treated controls. This reflected an initial slight hyperactivity in the Pfiesteria-treated animals followed by a decrease to control levels, Pfiesteria effects in the figure-8 maze and in early radial-arm maze training may be useful in a rapid screen for identifying the critical toxin(s) of Pfiesteria in future studies. Published by Elsevier Science Inc. C1 Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. N Carolina State Univ, Durham VA Med Ctr, Raleigh, NC 27695 USA. N Carolina State Univ, Dept Bot, Raleigh, NC 27695 USA. US EPA, Res Triangle Pk, NC 27711 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Levin, ED (reprint author), Duke Univ, Med Ctr, Dept Psychiat, 341 Bell Bldg,Box 3412, Durham, NC 27710 USA. NR 13 TC 25 Z9 26 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 1999 VL 21 IS 3 BP 215 EP 221 DI 10.1016/S0892-0362(98)00041-5 PG 7 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 202XP UT WOS:000080677700001 PM 10386824 ER PT J AU John, CS Bowen, WD Fisher, SJ Lim, BB Geyer, BC Vilner, BJ Wahl, RL AF John, CS Bowen, WD Fisher, SJ Lim, BB Geyer, BC Vilner, BJ Wahl, RL TI Synthesis, in vitro pharmacologic characterization, and preclinical evaluation of N-[2-(1 '-piperidinyl)ethyl]-3-[I-125]iodo-4-methoxybenzamide (P[I-125]MBA) for imaging breast cancer SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE breast cancer; imaging; sigma receptor ligands ID MALIGNANT-MELANOMA; RECEPTORS; CARCINOMA; BINDING; PROLIFERATION; SIGMA-1 AB The goal of this study was to investigate the potential use of a radioiodinated benzamide, N-[2-(1'-piperidinyl)ethyl]-3-iodo[I-125]-4-methoxybenzamide (P[I-125]MBA), a sigma receptor binding radioligand for imaging breast cancer. The chemical and radiochemical syntheses of PIMBA are described. The pharmacological evaluation of PIMBA was carried out for sigma-1 and sigma-2 receptor sites. The in vivo pharmacokinetics of the radioiodinated benzamide were determined in rats and comparison of P[I-125]MBA with Tc-99m sestamibi were made in a rat mammary tumor model. Sigma-1 affinity (K-i) for PIMBA in guinea pig brain membranes using [H-3](+)pentazocine was found to be 11.82 +/- 0.68 nM, whereas sigma-2 affinity in rat liver using [H-3]DTG (1,3-o-di-tolylguanidine) was 206 +/- 11 nM. Sites in guinea pig brain membranes labeled by P[I-125]MBA showed high affinity for haloperidol, (+)-pentazocine, BD1008, and PIMBA (K-i = 4.87 +/- 1.49, 8.81 +/- 1.97, 0.057 +/- 0.005, 46.9 +/- 1.8 nM, respectively). Competition binding studies were carried out in human ductal breast carcinoma cells (T47D). A dose dependent inhibition of specific binding was observed with several sigma ligands. K-i values for the inhibition of P[I-125]MBA binding in T47D cells for haloperidol, N-[2-(1'-piperidinyl)]ethyl]4-iodobenzamide (IPAB), N-(N-benzylpiperidin-4-yl)-4-iodobenzamide (4-IBP), and PIMBA were found to be 1.30 +/- 0.07, 13 +/- 1.5, 5.19 +/- 2.3, 1.06 +/- 0.5 nM, respectively. The in vitro binding data in guinea pig brain membranes and breast cancer cells confirmed binding to sigma sites. The saturation binding of P[I-125]MBA in T47D cells as studied by Scatchard analysis showed saturable binding, with a K-d = 94 +/- 7 nM and a B-max = 2035 +/- 305 fmol/mg of proteins. Biodistribution studies in Sprague-Dawley rats showed a rapid clearance of P[I-125]MBA from the normal organs. The potential of PIMBA in imaging breast cancer was evaluated in Lewis rats bearing syngeneic RMT breast cancers, a cancer that closely mimics human breast cancer histology. At 1 h postinjection, tumor uptake for P[I-125]MBA and Tc-99m sestamibi were found to be 0.35 +/- 0.01 and 0.32 +/- 0.01 % injected dose/organ (%ID/g), respectively. The %ID/g for liver, kidneys, and heart were 2, 11, and 20 times lower, respectively, for P[I-125]MBA as compared with Tc sestamibi. Slightly higher uptake of P[I-125]MBA in tumors (than Tc-sestamibi) and a low nontarget organ uptake warrants further studies of this and other sigma receptor ligands for their use as breast cancer imaging agents. NUCL MED BIOL 26;4:377-382, 1999. (C) 1999 Elsevier Science Inc. All rights reserved. C1 George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20037 USA. NIDDK, Unit Receptor Biochem & Pharmacol, Med Chem Lab, NIH, Bethesda, MD USA. Univ Michigan, Ann Arbor, MI USA. RP John, CS (reprint author), George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, 530 Ross Hall,2300 I St NW, Washington, DC 20037 USA. FU NCI NIH HHS [CA-58496, CA-52880] NR 20 TC 26 Z9 30 U1 0 U2 4 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 MAY PY 1999 VL 26 IS 4 BP 377 EP 382 DI 10.1016/S0969-8051(98)00104-8 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 196JE UT WOS:000080304600006 PM 10382840 ER PT J AU Bennett, PH AF Bennett, PH TI Type 2 diabetes among the Pima Indians of Arizona: An epidemic attributable to environmental change? SO NUTRITION REVIEWS LA English DT Article; Proceedings Paper CT 2nd Nestle Conference on Nutrition-Gene Interactions in Human Populations - The American Case CY JAN 29-30, 1998 CL MEXICO CITY, MEXICO SP Natl Nutr Inst Mexico, Mexican Fdn Hlth, Nestle Fund Nutr ID THRIFTY PHENOTYPE; MELLITUS; OBESITY; ASSOCIATION; MORTALITY; NIDDM C1 NIDDKD, NIH, Phoenix, AZ 85014 USA. RP Bennett, PH (reprint author), NIDDKD, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. NR 17 TC 32 Z9 32 U1 0 U2 4 PU INT LIFE SCIENCES INST PI LAWRENCE PA 810 EAST 10TH ST SUBSCRIPTION OFFICE, LAWRENCE, KS 66044 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD MAY PY 1999 VL 57 IS 5 BP S51 EP S54 PN 2 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 206ZX UT WOS:000080911800013 PM 10391026 ER PT J AU Valencia, ME Bennett, PH Ravussin, E Esparza, J Fox, C Schulz, LO AF Valencia, ME Bennett, PH Ravussin, E Esparza, J Fox, C Schulz, LO TI The Pima Indians in Sonora, Mexico SO NUTRITION REVIEWS LA English DT Article; Proceedings Paper CT 2nd Nestle Conference on Nutrition-Gene Interactions in Human Populations - The American Case CY JAN 29-30, 1998 CL MEXICO CITY, MEXICO SP Natl Nutr Inst Mexico, Mexican Fdn Hlth, Nestle Fund Nutr ID DIABETES-MELLITUS; PHYSICAL-ACTIVITY; OBESITY C1 Ctr Invest Alimentac & Desarrollo, AC Hermosillo, Sonora, Mexico. NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA. Univ Wisconsin, Milwaukee, WI 53201 USA. RP Valencia, ME (reprint author), Ctr Invest Alimentac & Desarrollo, AC Hermosillo, Sonora, Mexico. NR 15 TC 27 Z9 28 U1 0 U2 0 PU INT LIFE SCIENCES INST PI LAWRENCE PA 810 EAST 10TH ST SUBSCRIPTION OFFICE, LAWRENCE, KS 66044 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD MAY PY 1999 VL 57 IS 5 BP S55 EP S57 PN 2 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 206ZX UT WOS:000080911800014 PM 10391027 ER PT J AU Bishop, MR AF Bishop, MR TI The Champlin et al article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID BONE-MARROW TRANSPLANTATION; GRAFT-VERSUS-LEUKEMIA; CHEMOTHERAPY; MALIGNANCY C1 NCI, Bethesda, MD 20892 USA. RP Bishop, MR (reprint author), NCI, Bethesda, MD 20892 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD MAY PY 1999 VL 13 IS 5 BP 631 EP + PG 2 WC Oncology SC Oncology GA 392WB UT WOS:000166434600009 ER PT J AU Moore, CE Wiatrak, BJ McClatchey, KD Koopmann, CF Thomas, GR Bradford, CR Carey, TE AF Moore, CE Wiatrak, BJ McClatchey, KD Koopmann, CF Thomas, GR Bradford, CR Carey, TE TI High-risk human papillomavirus types and squamous cell carcinoma in patients with respiratory papillomas SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID POLYMERASE CHAIN-REACTION; LARYNGEAL PAPILLOMAS; INSITU HYBRIDIZATION; CERVICAL-CANCER; DNA; TRACT; JUVENILE; AMPLIFICATION; ASSOCIATION; INFECTIONS AB Respiratory papillomas (RPs) are benign, virally induced tumors of the larynx and respiratory epithelium that may obstruct the airway and tend to recur frequently. RPs are thought to be the result of infection with the human papillomaviruses (HPVs) types 6 and 11. We surveyed archival RP specimens to determine whether there were correlations of HPV type with patient characteristics or clinical course. Paraffin-embedded papilloma specimens of 45 different patients were analyzed. We assessed HPV types using the polymerase chain reaction with E6 consensus primers, hybrid capture assays (high or low risk), and dot blot hybridization of generic E6 PCR products with E6 type-specific oligonucleotide probes, The presence and type of HPV were correlated with patient data from a retrospective chart review, We found that RPs may have either low- or high-risk HPV types and some contain multiple HPV types. Respiratory infection with high-risk HPV apparently introduces a long-term risk of squamous cell carcinoma development, even in the absence of conventional cofactors. Low-risk HPV infection may also act in association with these cofactors to promote carcinogenesis, Our data also show a racial imbalance in RP that may indicate a difference in genetic resistance and/or susceptibility to HPV infection and the development of RP. C1 Emory Hlth Syst, Dept Otolaryngol, Atlanta, GA 30335 USA. Grady Mem Hosp, Atlanta, GA 30335 USA. Univ Alabama, Dept Pediat Otolaryngol, Birmingham, AL USA. Univ Michigan, Ctr Med, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Med, Dept Otolaryngol, Ann Arbor, MI 48109 USA. Natl Inst Hlth, Bethesda, MD USA. RP Moore, CE (reprint author), Emory Hlth Syst, Dept Otolaryngol, 80 Butler St SE, Atlanta, GA 30335 USA. OI Carey, Thomas/0000-0002-5202-7518 NR 43 TC 25 Z9 25 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD MAY PY 1999 VL 120 IS 5 BP 698 EP 705 DI 10.1053/hn.1999.v120.a91773 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 194EN UT WOS:000080179300014 PM 10229596 ER PT J AU Peruselli, C Di Giulio, P Toscani, F Gallucci, M Brunelli, C Costantini, M Tamburini, M Paci, E Miccinesi, G Addington-Hall, JM Higginson, IJ AF Peruselli, C Di Giulio, P Toscani, F Gallucci, M Brunelli, C Costantini, M Tamburini, M Paci, E Miccinesi, G Addington-Hall, JM Higginson, IJ TI Home palliative care for terminal cancer patients: a survey on the final week of life SO PALLIATIVE MEDICINE LA English DT Article DE palliative care; home care services; neoplasms; sedation (non-MeSH); terminal care ID MULTICENTER AB As part of a large multicentre study on palliative care units in Italy, carried out between 1 January and 30 June 1995, we describe the place, circumstances and 'quality of death' of patients admitted to home palliative care. Data presented refer to 401 patients (67% of the 601 patients randomly selected for evaluation). Of these 401 patients 303 (76%) died at home. According to the Support Team Assessment Schedule (STAS) pain was fairly well controlled during the final week of life, while the control of other symptoms appeared to be less satisfactory invasive procedures were undertaken on 56% of patients, while in hospital the percentage increased to 75%. Twenty-five per cent of patients were totally pharmacologically sedated during the final 12 h of life. Neither the number of symptoms nor other factors were apparently associated with the decision to sedate the patient. The wide variations in the frequency of sedation among centres suggest that the choice to sedate the patient may reflect the provider's behaviour or services' policy rather than the patients' preference or needs. The definition of common criteria and guidelines for sedation of patients should be one of the topics for discussion among palliative care teams. C1 Merate Hosp, Palliat Care Serv, Palliat Care Unit, I-22055 Merate, Lc, Italy. Mario Negri Inst, Nursing Res Unit, Milan, Italy. Cremona Hosp, Palliat Care Unit, Genoa, Italy. Desio Hosp, Palliat Care Unit, Genoa, Italy. Natl Canc Inst, Psychol Div, Genoa, Italy. Natl Canc Inst, Dept Epidemiol, Genoa, Italy. Ctr Study & Prevent Canc, Dept Epidemiol, Florence, Italy. Univ London Kings Coll, Sch Med & Dent, Dept Palliat Care & Policy, London, England. RP Peruselli, C (reprint author), Merate Hosp, Palliat Care Serv, Palliat Care Unit, Lgo Mand 1, I-22055 Merate, Lc, Italy. RI Higginson, Irene/C-7309-2012; costantini, massimo/G-1443-2012; Brunelli , Cinzia/B-9361-2017; OI Brunelli , Cinzia/0000-0003-3905-1289; costantini, massimo/0000-0002-5293-7079 NR 20 TC 60 Z9 60 U1 0 U2 2 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0269-2163 J9 PALLIATIVE MED JI Palliat. Med. PD MAY PY 1999 VL 13 IS 3 BP 233 EP 241 DI 10.1191/026921699669863369 PG 9 WC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medicine, General & Internal SC Health Care Sciences & Services; Public, Environmental & Occupational Health; General & Internal Medicine GA 207KG UT WOS:000080935600006 PM 10474710 ER PT J AU Bundy, DAP Gottlieb, M AF Bundy, DAP Gottlieb, M TI Parasitic infection in China: Farewell to the god of plagues SO PARASITOLOGY TODAY LA English DT News Item C1 Univ Oxford, Wellcome Trust Ctr Epidemiol Infect Dis, Oxford OX1 3PS, England. NIAID, Parasitol & Int Program Branch, Div Microbiol & Infect Dis, Bethesda, MD 20892 USA. RP Bundy, DAP (reprint author), Univ Oxford, Wellcome Trust Ctr Epidemiol Infect Dis, S Parks Rd, Oxford OX1 3PS, England. NR 7 TC 5 Z9 5 U1 0 U2 0 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 MAY PY 1999 VL 15 IS 5 BP 170 EP 172 DI 10.1016/S0169-4758(99)01434-9 PG 3 WC Parasitology SC Parasitology GA 215KW UT WOS:000081381700001 PM 10322345 ER PT J AU Li, P Patel, H Tabibi, SE Vishnuvajjala, R Yalkowsky, SH AF Li, P Patel, H Tabibi, SE Vishnuvajjala, R Yalkowsky, SH TI Evaluation of intravenous flavopiridol formulations SO PDA JOURNAL OF PHARMACEUTICAL SCIENCE AND TECHNOLOGY LA English DT Article AB Flavopiridol is currently under consideration as a parenteral treatment of breast tumors. The solubility of this poorly water-soluble compound can be increased by a number of methods. However because of its low water solubility, precipitation of the solubilized drug upon injection can be a problem. The potential of several flavopiridol formulations to precipitate is evaluated using a static serial dilution technique. If is shown that formulations containing up to 10 mg/mL of flavopiridol which produce negligible precipitation on dilution can be developed. C1 Univ Arizona, Coll Pharm, Dept Pharmaceut Sci, Tucson, AZ 85721 USA. NCI, Bethesda, MD 20892 USA. RP Li, P (reprint author), Univ Arizona, Hlth Sci Ctr, 1703 E Mabel St,POB 210207, Tucson, AZ 85721 USA. NR 9 TC 7 Z9 7 U1 0 U2 1 PU PARENTERAL DRUG ASSOC INC PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 620, BETHESDA, MD 20814 USA SN 1076-397X J9 PDA J PHARM SCI TECH JI PDA J. Pharm. Sci. Technol. PD MAY-JUN PY 1999 VL 53 IS 3 BP 137 EP 140 PG 4 WC Engineering, Biomedical; Pharmacology & Pharmacy SC Engineering; Pharmacology & Pharmacy GA 221MR UT WOS:000081731300007 PM 10754703 ER PT J AU Henske, EP Thorner, P Patterson, K Zhuang, ZP Bernstein, J AF Henske, EP Thorner, P Patterson, K Zhuang, ZP Bernstein, J TI Renal cell carcinoma in children with diffuse cystic hyperplasia of the kidneys SO PEDIATRIC AND DEVELOPMENTAL PATHOLOGY LA English DT Article DE renal cell carcinoma; polycystic kidney; tuberous sclerosis; von Hippel-Lindau disease ID TUBEROUS SCLEROSIS COMPLEX; TUMOR-SUPPRESSOR GENE; DISEASE; IDENTIFICATION; MUTATIONS; LESIONS; MODEL AB We report the clinical, pathologic, and genetic features of renal malignancy in two children with diffuse cystic hyperplasia. Both presented with massive bilateral nephromegaly. Neither had a family history or clinical findings suggestive of tuberous sclerosis or von Hippel-Lindau disease. The kidneys of both children were extensively replaced by tubulocystic hyperplasia with large eosinophilic epithelial cells. The masses of hyperplastic tissue were nodular, compressing remnants of uninvolved renal parenchyma. Tubulopapillary carcinoma was present in both children, one of whom had bilateral multicentric carcinoma. No loss of heterozygosity was detected in the tumors at the TSC1, TSC2, or VHL gene regions, and no alterations in the VHL gene were detected using single-strand conformation polymorphism analysis. These cases of bilateral renal enlargement with diffuse cystic hyperplasia appear to represent a new clinical syndrome that may warrant bilateral nephrectomy because of the risk of malignancy. C1 Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. Hosp Sick Children, Div Pathol, Dept Pediat Lab Med, Toronto, ON M5G 1X8, Canada. Childrens Hosp & Med Ctr, Dept Pathol, Seattle, WA 98105 USA. NCI, Dept Pathol, Bethesda, MD 20892 USA. William Beaumont Res Inst, Royal Oak, MI 48073 USA. RP Henske, EP (reprint author), Fox Chase Canc Ctr, Dept Med Oncol, 7701 Burholme Ave, Philadelphia, PA 19111 USA. NR 20 TC 5 Z9 5 U1 0 U2 1 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1093-5266 EI 1615-5742 J9 PEDIATR DEVEL PATHOL JI Pediatr. Dev. Pathol. PD MAY-JUN PY 1999 VL 2 IS 3 BP 270 EP 274 DI 10.1007/s100249900123 PG 5 WC Pathology; Pediatrics SC Pathology; Pediatrics GA 183LX UT WOS:000079556000012 PM 10191351 ER PT J AU McIntosh, K Cooper, E Xu, J Mirochnick, M Lindsey, J Jacobus, D Mofenson, L Yogev, R Spector, SA Sullivan, JL Sacks, H Kovacs, A Nachman, S Sleasman, J Bonagura, V McNamara, J AF McIntosh, K Cooper, E Xu, J Mirochnick, M Lindsey, J Jacobus, D Mofenson, L Yogev, R Spector, SA Sullivan, JL Sacks, H Kovacs, A Nachman, S Sleasman, J Bonagura, V McNamara, J CA ACTG 179 Study Team TI Toxicity and efficacy of daily vs. weekly dapsone for prevention of Pneumocystis carinii pneumonia in children infected with human immunodeficiency virus SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE dapsone; pediatric human immunodeficiency virus; infection; Pneumocystis carinii pneumonia ID AEROSOLIZED PENTAMIDINE; RANDOMIZED TRIAL; PROPHYLAXIS; PHARMACOKINETICS; ENCEPHALITIS; SAFETY; AIDS AB Background. Dapsone is an alternative drug for Pneumocystis carinii pneumonia (PCP) prophylaxis in individuals intolerant to trimethoprimsulfamethoxazole (T/S). There are, however, few data on the pharmacokinetics, toxicity or efficacy of dapsone in children. Design. Randomized, multicenter trial comparing daily (1 or 2 mg/kg) with weekly (4 mg/kg) dapsone regimens in 94 HIV-infected children intolerant to T/S. Methods. Hematologic and hepatic toxicity was monitored, as well as the occurrence of skin rash, PCP or death. Results. Initial pharmacokinetic data indicated that adequate serum dapsone concentrations were not achieved with the daily 1-mg/kg regimen; the daily dose was then increased to 2 mg/kg. Both short and long term hematologic toxicities were marginally greater in children receiving the daily 2 mg/kg compared with the weekly regimen. Allergic skin rashes were similar in children receiving the daily and weekly regimens (17% in both) and were not associated with prior history of rash with T/S. PCP occurred most frequently with the daily 1-mg/kg regimen (22.0 cases/100 patient years), least frequently with the daily 2-mg/kg regimen (0 case/100 patient years) and at intermediate frequency with the weekly regimen (9.5 cases/100 patient years). More deaths were observed in patients receiving the daily than the weekly regimen (8 vs. 2, respectively), although the deaths were not directly attributable to dapsone treatment. Conclusion. Although a weekly dapsone regimen of 4 mg/kg produced less hematologic toxicity than a daily regimen of 2 mg/kg, this advantage was offset by a trend toward higher breakthrough rates of PCP. C1 Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. Boston Med Ctr, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Jacobus Pharmaceut Co Inc, Princeton, NJ USA. NICHHD, Bethesda, MD 20892 USA. Childrens Mem Hosp, Chicago, IL 60614 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. Mt Sinai Sch Med, New York, NY USA. Univ So Calif, Med Ctr, Los Angeles, CA USA. SUNY Stony Brook, Hlth Sci Ctr, Stony Brook, NY 11794 USA. Univ Florida, Coll Med, Gainesville, FL USA. Schneider Childrens Hosp, Long Isl Jewish Med Ctr, New Hyde Park, NY USA. NIAID, Div Aids, Bethesda, MD 20892 USA. RP McIntosh, K (reprint author), Childrens Hosp, Div Infect Dis, 300 Longwood Ave, Boston, MA 02115 USA. OI Mofenson, Lynne/0000-0002-2818-9808 NR 27 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD MAY PY 1999 VL 18 IS 5 BP 432 EP 439 DI 10.1097/00006454-199905000-00007 PG 8 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 196TG UT WOS:000080323200006 PM 10353516 ER PT J AU Crowell, D Kulp, T Kapuniai, L Hunt, C Hoppenbrouwers, T Brooks, L Tinsley, L Silvestri, J Ward, SD Golub, H Peucker, M Corwin, M Willinger, M AF Crowell, D Kulp, T Kapuniai, L Hunt, C Hoppenbrouwers, T Brooks, L Tinsley, L Silvestri, J Ward, SD Golub, H Peucker, M Corwin, M Willinger, M CA CHIME Study Grp TI Infant polysomnography: Arousal identification and scoring reliability SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Univ Hawaii Manoa, Honolulu, HI 96822 USA. Kapiolani Med Ctr Women & Children, Honolulu, HI USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. Med Coll Ohio, Toledo, OH 43699 USA. USC, Sch Med, Los Angeles, CA USA. USC, Los Angeles Cty Med Ctr, Womens & Childrens Hosp, Childrens Hosp Los Angeles, Los Angeles, CA USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Camden, NJ 08103 USA. Rush Univ, Rush Med Coll, Chicago, IL 60612 USA. NICHHD, Pregnancy & Perinatol Branch, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD MAY PY 1999 VL 45 IS 5 MA 166 BP 42A EP 42A DI 10.1203/00006450-199905020-00166 PN 2 PG 1 WC Pediatrics SC Pediatrics GA 192PT UT WOS:000080088200167 ER PT J AU Metcalfe, DD AF Metcalfe, DD TI Mastocytosis and the clinical implications of mutations in C-kit SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD MAY PY 1999 VL 45 IS 5 MA 17 BP 745 EP 745 DI 10.1203/00006450-199905010-00047 PN 1 PG 1 WC Pediatrics SC Pediatrics GA 192PC UT WOS:000080086700046 ER PT J AU Nelson, DL AF Nelson, DL TI The new understanding of the primary immunodeficiency diseases SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NCI, Metab Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD MAY PY 1999 VL 45 IS 5 MA 19 BP 746 EP 746 DI 10.1203/00006450-199905010-00049 PN 1 PG 1 WC Pediatrics SC Pediatrics GA 192PC UT WOS:000080086700048 ER PT J AU Brown, KE AF Brown, KE TI Basic and clinical aspects of intrauterine parvovirus B19 infection SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD MAY PY 1999 VL 45 IS 5 MA 169 BP 771 EP 771 DI 10.1203/00006450-199905010-00199 PN 1 PG 1 WC Pediatrics SC Pediatrics GA 192PC UT WOS:000080086700198 ER PT J AU Brenner, RA Overpeck, MD Trumble, AC DerSimonian, R Berendes, H AF Brenner, RA Overpeck, MD Trumble, AC DerSimonian, R Berendes, H TI Deaths attributable to injuries in infants, United States, 1983-1991 SO PEDIATRICS LA English DT Article DE infant; injury; suffocation; motor vehicle; homicide; drowning; inhalation; fire ID CHILD-ABUSE; RISK-FACTORS; RANDOMIZED TRIAL; HOME VISITATION; MORTALITY; HOMICIDE; CERTIFICATES; VALIDATION; ACCIDENTS; YOUNGER AB Objective To describe risk factors for injury death among infants in the United States by the specific external cause of death. Methods. Data were analyzed from the US-linked birth/infant death files for the years 1983-1991. Potential risk factors for injury death were identified from birth certificate data and included both maternal and infant factors. Injury rates were calculated by external cause of death. Characteristics of infants who died from an injury were compared with those of the entire birth cohort. The independent effect of potential risk factors was assessed in multivariate analyses using a case-control study design. Results. A total of 10 370 injury deaths were identified over the 9-year study period (29.72/100 000 live births). The leading causes of death were homicide, suffocation, motor vehicle crashes, and choking (inhalation of food or objects). There was no significant temporal trend in the overall rate of injury death; however, this was because significant increases in the rates of death from homicide (6.4%/year) and mechanical suffocation (3.7%/year) were offset by decreases in rates of death from fires (-4.7%/year) and choking (-4.6%/year). In adjusted analyses, infants born to mothers with no prenatal care, <12 years of education, two or more previous live births, Native American race, or <20 years of age were at twice the risk of injury death compared with the lowest risk groups (initiation of prenatal care in the first trimester, greater than or equal to 16 years of education, no previous live births, white, or greater than or equal to 25 years of age). When analyzed by the specific cause of death, the factors that were associated most strongly with death varied. For example, Native Americans were at greatest risk of a motor vehicle related death (compared with whites: OR: 3.6; 95% CI: 1.8-7.1), and infants with birth weights of <1500 g were at greatest risk of death attributable to inhalation of food (compared with greater than or equal to 2500 g: OR: 9.6; 95% CI: 3.3-28.0) or objects (OR: 11.8; 95% CI: 4.5-30.5). Conclusion. A number of sociodemographic characteristics are associated with an increased risk of injury-related death in infants. The strength of associations between specific risk factors and death varies with the external cause of death, thus identifying high-risk subgroups for targeting of cause-specific interventions and simultaneously increasing our understanding of the individual and societal mechanisms underlying these tragedies. C1 NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. RP Brenner, RA (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Room 7b03, Bethesda, MD 20892 USA. NR 38 TC 48 Z9 49 U1 2 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 MAY PY 1999 VL 103 IS 5 BP 968 EP 974 DI 10.1542/peds.103.5.968 PG 7 WC Pediatrics SC Pediatrics GA 193JZ UT WOS:000080134300006 PM 10224174 ER PT J AU Kline, MW Van Dyke, RB Lindsey, JC Gwynne, M Culnane, M Diaz, C Yogev, R McKinney, RE Abrams, EJ Mofenson, LM AF Kline, MW Van Dyke, RB Lindsey, JC Gwynne, M Culnane, M Diaz, C Yogev, R McKinney, RE Abrams, EJ Mofenson, LM CA Pediat AIDS Clin Trials Grp 327 Team TI Combination therapy with stavudine (d47) plus didanosine (ddI) in children with human immunodeficiency virus infection SO PEDIATRICS LA English DT Article DE stavudine; didanosine; HIV infection; infant or child ID ORAL ZIDOVUDINE; SAFETY; TRIAL; AIDS AB Objectives. To evaluate the safety, tolerance, and antiviral activity of combination therapy with stavudine (d4T) plus didanosine (ddI) in symptomatic human immunodeficiency virus (HIV)-infected children. Methods. The study enrolled HIV-infected children who successfully completed Pediatric AIDS Clinical Trials Group (PACTG) protocol 240 (d4T versus zidovudine [ZDV] monotherapy) without disease progression or who had received ZDV monotherapy by prescription for at least the preceding 6 months. Children who had received d4T monotherapy in PACTG 240 were assigned to treatment with d4T plus ddI (arm 1). Children who had received ZDV monotherapy in PACTG 240 or by prescription were randomized in a double-blind manner to treatment with either d4T alone (arm 2) or d4T plus ddI (arm 3). patients were followed for 48 weeks each. Results, A total of 108 children were enrolled. The mean age was 5.0 years (range, 1.6 to 11.5 years), with mean baseline plasma HIV RNA concentration and CD4(+) lymphocyte count of 4.6 log(10) copies/mL (range, 2.6 to 5.9 log(10) copies/mL) and 819 cells/mu L (range, 8 to 3431 cells/mu L), respectively. Both d4T monotherapy and d4T plus ddI combination therapy were well-tolerated, with 96 (89%) patients completing 48 weeks of study treatment. Plasma HIV RNA concentrations showed larger average declines in arm 3 compared with arm 2 at study week 12 (0.49 vs 0.18 log(10) copies/mL, respectively); these average declines were maintained through week 48 (0.51 vs 0.17 log(10) copies/mL, respectively). Fewer than 8% of the patients in any of the treatment arms had plasma HIV RNA concentrations below the limit of quantification (200 copies/mL) at any time point. Conclusions. Combination therapy with d4T plus ddI is safe and well-tolerated in HIV-infected children, producing durable, but incomplete, suppression of virus replication. This combination of nucleoside antiretroviral agents may provide a valuable backbone to protease inhibitor-containing treatment regimens for HIV-infected children. C1 Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Texas Childrens Hosp, Houston, TX 77030 USA. Tulane Univ, Sch Med, Dept Pediat, New Orleans, LA 70112 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. Pediat ACTG Operat Ctr, Rockville, MD USA. NIAID, Bethesda, MD 20892 USA. Univ Puerto Rico, Dept Pediat, San Juan, PR 00936 USA. Childrens Mem Hosp, Dept Pediat, Chicago, IL 60614 USA. Northwestern Univ, Sch Med, Chicago, IL USA. Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. Harlem Hosp Med Ctr, Dept Pediat, New York, NY USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, Rockville, MD USA. RP Kline, MW (reprint author), Baylor Coll Med, Dept Pediat, 1 Baylor Plaza, Houston, TX 77030 USA. NR 16 TC 10 Z9 10 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 MAY PY 1999 VL 103 IS 5 BP art. no. EP e62 DI 10.1542/peds.103.5.e62 PG 6 WC Pediatrics SC Pediatrics GA 193JZ UT WOS:000080134300022 PM 10224206 ER PT J AU De Cupis, A Schettini, G Favoni, RE AF De Cupis, A Schettini, G Favoni, RE TI New vs old fashioned oestradiol antagonists in mammary carcinoma: 'In vitro' and 'in vivo' pharmacological approaches SO PHARMACOLOGICAL RESEARCH LA English DT Article DE breast cancer; oestrogens; antioestrogens; endocrinotherapy ID HUMAN-BREAST-CANCER; SURGICAL-ADJUVANT-BREAST; HUMAN ESTROGEN-RECEPTOR; ANTIESTROGEN ICI-182780; CHEMOPREVENTIVE AGENTS; CLINICAL APPRAISAL; PURE ANTIESTROGENS; GROWTH-FACTORS; TAMOXIFEN; PREVENTION AB The rationale underlying therapeutic strategies designed to inhibit the action of endogenous sex hormones in malignant breast cells is provided by the demonstration of their involvement in supporting the development and growth of breast carcinoma. The surgical removal of steroid-secreting glands, in order to reduce the level of oestrogens reaching their target tissues, has for years been substituted by the so-called endocrinotherapeutic approach, which is based on the counteraction of the steroid hormone activity by the hormonal receptor blockade with suitable antioestrogenic compounds. Over the past 25 years, the non-steroidal oestrogen antagonist tamoxifen has become the standard endocrine treatment for breast cancer. The triphenylethylene-derivative compound competes efficiently for binding to the oestrogen receptor, but the complex retains some transcriptional activity. Consequently, tamoxifen exhibits, both 'in vitro and in vivo', a range of biological activity from full oestrogen antagonism to partial agonism. There is also evidence suggesting that the agonist activity of this compound may ultimately stimulate breast tumour growth, thus causing some treatment failures. Moreover, the use of tamoxifen is limited by the possible onset of drug-resistance in many patients. Nevertheless, widely tested tamoxifen has proved to be very helpful for the development of new compounds to be used as long-term adjuvant therapy or as preventive agents. These novel oestrogen antagonists belong to two major classes: tamoxifen analogs and new pure steroidal-like antioestrogens. The search for and development of compounds devoid of tamoxifen cross-resistance, with a safer toxicity profile as well as the lack of oestrogenic effects, provide the bases to improve the current therapeutic applications of antioestrogens. (C) 1999 Academic Press. C1 Univ Genoa, Natl Canc Inst, Dept Preclin Oncol, Lab Pharmacol & Neurosci, I-16132 Genoa, Italy. Univ Genoa, Dept Clin & Expt Oncol, Adv Biotechnol Ctr, I-16132 Genoa, Italy. RP Favoni, RE (reprint author), Univ Genoa, Natl Canc Inst, Dept Preclin Oncol, Lab Pharmacol & Neurosci, Largo Rosanna Benzi 10, I-16132 Genoa, Italy. NR 62 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-6618 J9 PHARMACOL RES JI Pharmacol. Res. PD MAY PY 1999 VL 39 IS 5 BP 335 EP 344 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 205AG UT WOS:000080798600002 PM 10328990 ER PT J AU Marquez, VE Nacro, K Benzaria, S Lee, J Sharma, R Teng, K Milne, GWA Bienfait, B Wang, SM Lewin, NE Blumberg, PM AF Marquez, VE Nacro, K Benzaria, S Lee, J Sharma, R Teng, K Milne, GWA Bienfait, B Wang, SM Lewin, NE Blumberg, PM TI The transition from a pharmacophore-guided approach to a receptor-guided approach in the design of potent protein kinase C ligands SO PHARMACOLOGY & THERAPEUTICS LA English DT Article; Proceedings Paper CT 1st International Conferenc on Inhibitors of Protein Kinases (IPK 98) CY SEP 15-20, 1998 CL WARSAW, POLAND SP State Comm Sci Res, Minist Natl Educ, Int Union Biochem & Molec Biol, Parke-Davis Pharmaceut Res, Zeneca Pharmaceut, Novartis Pharmaceut, Medivir AB, Huddinge, ISIS Pharmaceut, Agouron Pharmaceut, Procter & Gamble, Polish Bank Dev, Tripos Inc, Molec Simulat Inc DE protein kinase C (PKC); PKC isozymes; PKC activation; PKC binding; diacylglycerol; diacylglycerol lactones ID CONFORMATIONALLY CONSTRAINED ANALOGS; GAMMA-BUTYROLACTONE SKELETON; RIGID DIACYLGLYCEROL ANALOGS; 5-DISUBSTITUTED TETRAHYDRO-2-FURANONE TEMPLATE; CYSTEINE-RICH DOMAIN; PK-C; PHORBOL ESTER; BINDING-AFFINITY; TUMOR PROMOTERS; DELTA-LACTONES AB The pharmacophore-guided approach used in the first phase of the design of novel protein kinase C (PKC) ligands was based on the study of the geometry of bioequivalent pharmacophores present in diacylglycerol (DAG) and in the more potent phorbol ester tumor promoters. A number of potent DAG lactones were generated by this approach, in which the glycerol backbone was constrained into various heterocyclic rings to reduce the entropic penalty associated with DAG binding. Based on the information provided by X-ray and NMR structures of the cysteine-rich, CI phorbol ester/DAG binding domain, the DAG lactones were further modified to optimize their interaction with a group of highly conserved hydrophobic amino acids along the rim of the C1 domain. This receptor-guided approach culminated with the synthesis of a series of "super DAG" molecules that can bind to PKC with low nanomolar affinities. These compounds provide insight into the basis for PKC ligand specificity. Moreover, some of the compounds reviewed herein show potential utility as antitumor agents. (C) 1999 Elsevier Science Inc. All rights reserved. C1 NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Marquez, VE (reprint author), NCI, Med Chem Lab, NIH, Bldg 37,Rm 5C-02,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. NR 54 TC 40 Z9 41 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD MAY-JUN PY 1999 VL 82 IS 2-3 BP 251 EP 261 DI 10.1016/S0163-7258(98)00048-5 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 207DK UT WOS:000080920000014 PM 10454202 ER PT J AU Sausville, EA Zaharevitz, D Gussio, R Meijer, L Louarn-Leost, M Kunick, C Schultz, R Lahusen, T Headlee, D Stinson, S Arbuck, SG Senderowicz, A AF Sausville, EA Zaharevitz, D Gussio, R Meijer, L Louarn-Leost, M Kunick, C Schultz, R Lahusen, T Headlee, D Stinson, S Arbuck, SG Senderowicz, A TI Cyclin-dependent kinases: Initial approaches to exploit a novel therapeutic target SO PHARMACOLOGY & THERAPEUTICS LA English DT Article; Proceedings Paper CT 1st International Conferenc on Inhibitors of Protein Kinases (IPK 98) CY SEP 15-20, 1998 CL WARSAW, POLAND SP State Comm Sci Res, Minist Natl Educ, Int Union Biochem & Molec Biol, Parke-Davis Pharmaceut Res, Zeneca Pharmaceut, Novartis Pharmaceut, Medivir AB, Huddinge, ISIS Pharmaceut, Agouron Pharmaceut, Procter & Gamble, Polish Bank Dev, Tripos Inc, Molec Simulat Inc DE flavopiridol; cyclin-dependent kinase; phase I trial; benzodiazepine; COMPARE; drug treatment of neoplasms ID BREAST-CARCINOMA CELLS; PROTEIN-KINASE; FLAVOPIRIDOL; INHIBITOR; PHOSPHORYLATION; CDC2; L86-8275; CANCER; DEPHOSPHORYLATION; IDENTIFICATION AB Cyclin-dependent kinases (CDKs) have been recognized as key regulators of cell cycle progression. Alteration and deregulation of CDK activity are pathogenic hallmarks of neoplasia. Therefore, inhibitors or modulators would be of interest to explore as novel therapeutic agents in cancer, as well as other hyperproliferative disorders, Flavopiridol is a semisynthetic flavonoid that emerged from an empirical screening program as a potent antiproliferative agent that mechanistic studies demonstrated to directly inhibit CDKs 1, 2, and 4 as a competitive ATP site antagonist. Initial clinical trials have shown that concentrations that inhibit cell proliferation and CDK activity in vitro can be safely achieved in humans, and additional clinical trials will establish its clinical potential. To address the need for additional chemotypes that may serve as lead structures for drugs that would not have the toxicities associated with flavopiridol, compounds with a similar pattern of cell growth inhibitory activity in the National Cancer Institute's in vitro anticancer drug screen have been recognized by the computer-assisted pattern recognition algorithm COMPARE and then screened for anti-CDK activity in a biochemical screen. The benzodiazepine derivative NSC 664704 (7, 12-dihydro-indolo[3,2-d][1]benzazepin-6(5H)-one) was revealed by that approach as a moderately potent (IC50 0.4 mu M) inhibitor of CDK2, which in initial experiments shows evidence of causing cell cycle redistribution in living cells. NSC 664704 is, therefore, a candidate for further structural optimization, guided in part by understanding of the ATP-binding site in CDK2. This approach represents one way of combining empirical screening information with structure based design to derive novel candidate therapeutic agents directed against an important cellular target. (C) 1999 Elsevier Science Inc. All rights reserved. C1 NCI, Dev Therapeut Program, EPN 843, Div Canc Treatment & Diagnosis, Rockville, MD 20852 USA. CNRS, Cell Cycle Grp, Roscoff, France. Univ Hamburg, Inst Pharm, Hamburg, Germany. NCI, Di Canc Treatment & Diagnosis, Canc Therapy Evaluat Program, Rockville, MD 20852 USA. RP Sausville, EA (reprint author), NCI, Dev Therapeut Program, EPN 843, Div Canc Treatment & Diagnosis, 6130 Execut Blvd, Rockville, MD 20852 USA. NR 33 TC 100 Z9 104 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD MAY-JUN PY 1999 VL 82 IS 2-3 BP 285 EP 292 DI 10.1016/S0163-7258(98)00062-X PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 207DK UT WOS:000080920000018 PM 10454206 ER PT J AU Cho-Chung, YS AF Cho-Chung, YS TI Antisense oligonucleotide inhibition of serine threonine kinases: An innovative approach to cancer treatment SO PHARMACOLOGY & THERAPEUTICS LA English DT Article; Proceedings Paper CT 1st International Conferenc on Inhibitors of Protein Kinases (IPK 98) CY SEP 15-20, 1998 CL WARSAW, POLAND SP State Comm Sci Res, Minist Natl Educ, Int Union Biochem & Molec Biol, Parke-Davis Pharmaceut Res, Zeneca Pharmaceut, Novartis Pharmaceut, Medivir AB, Huddinge, ISIS Pharmaceut, Agouron Pharmaceut, Procter & Gamble, Polish Bank Dev, Tripos Inc, Molec Simulat Inc DE antisense oligonucleotide; cAMP-dependent protein kinase; protein kinase C; MAP kinase; cancer cells; growth inhibition ID DEPENDENT PROTEIN-KINASE; C-ALPHA EXPRESSION; MAMMARY EPITHELIAL-CELLS; REGULATORY SUBUNIT; MESSENGER-RNA; MOLECULAR-CLONING; GENE-EXPRESSION; DOWN-REGULATION; NUDE-MICE; ANTITUMOR-ACTIVITY AB The identification of genes that confer a growth advantage on neoplastic cells and the understanding of the genetic mechanism(s) responsible for their activation have made possible a direct genetic approach to cancer treatment using nucleic acid therapeutics. Moreover, the ability to block the expression of individual genes that promote carcinogenesis provides a powerful tool to explore the molecular basis of normal growth regulation, as well as the opportunity for therapeutic intervention. One technique for turning off a single activated gene is the use of antisense oligodeoxynucleotides and their analogs for inhibition of gene expression. The serine/threonine kinases are involved in mediating intracellular responses to external signals, such as growth factors, hormones, and neurotransmitters, and are involved in cell proliferation and oncogenesis. Described herein are recent studies supporting the potential use of oligonucleotides targeting these kinases as chemotherapeutic agents for cancer treatment. The serine/threonine kinases included here are protein kinase A, protein kinase C, and c-raf-1 kinase. Published by Elsevier Science Inc. C1 NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, NIH, Bldg 10,Rm 5B05, Bethesda, MD 20892 USA. NR 97 TC 23 Z9 23 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD MAY-JUN PY 1999 VL 82 IS 2-3 BP 437 EP 449 DI 10.1016/S0163-7258(98)00043-6 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 207DK UT WOS:000080920000030 PM 10454218 ER PT J AU Marshall, JG Dumbroff, EB Thatcher, BJ Martin, B Rutledge, RG Blumwald, E AF Marshall, JG Dumbroff, EB Thatcher, BJ Martin, B Rutledge, RG Blumwald, E TI Synthesis and oxidative insolubilization of cell-wall proteins during osmotic stress SO PLANTA LA English DT Article DE cell wall; osmotic stress; oxidative insolubilization; Pinus (root turgor); root polypeptides; turgor ID LOW WATER POTENTIALS; CROSS-LINKING; ABSCISIC-ACID; ISODITYROSINE; GLYCOPROTEIN; INDUCTION; EXTENSION; LEAVES; GROWTH; TURGOR AB The cell walls in the new white roots of jack pine (Pinus banksiana Lamb.) were observed to constrict around the shrinking protoplast of osmotically stressed roots, and pressure was maintained via an apparent adjustment of cell-wall size and elasticity. These elastic alterations of the cell wall permitted the root cells to maintain full turgor despite the loss of most of the water in the tissue. The constriction of the root cell wall around the dehydrating protoplasts to maintain turgor may reflect changes in cell wall structure. We found that these shrinking root cells synthesize and secrete into the intercellular fluid a set of proteins. These proteins become tightly associated (i.e. guanidine HCl- and sodium dodecyl sulfate-insoluble) with the cell wall but can be released from the matrix, after briefly boiling in 0.1% sodium dodecyl sulfate, by the combination of guanidine HCl, CaCl2 and dithiothreitol. However, these cell-wall proteins became insoluble with time. The proteins could subsequently be destructively extracted from the wall with acid NaClO2 treatments. After these proteins were incorporated into the cell walls, the roots adopted a new, smaller maximal tissue volume and elastic coefficients returned to normal levels. C1 Univ Toronto, Dept Bot, Toronto, ON M5S 3B2, Canada. Univ Waterloo, Dept Biol, Waterloo, ON N2L 3G1, Canada. NIMH, NIH, Bethesda, MD 20892 USA. Nat Reources Canada, Laurentian Forestry Ctr, Ste Foy, PQ G1V 4C7, Canada. RP Univ Toronto, Dept Bot, 25 Willcocks St, Toronto, ON M5S 3B2, Canada. EM jmarshal@botany.utorotno.ca RI Marshall, John /E-8974-2012 OI Marshall, John /0000-0002-7124-1448 NR 42 TC 26 Z9 26 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0032-0935 EI 1432-2048 J9 PLANTA JI Planta PD MAY PY 1999 VL 208 IS 3 BP 401 EP 408 DI 10.1007/s004250050575 PG 8 WC Plant Sciences SC Plant Sciences GA 203LD UT WOS:000080708400013 PM 10384730 ER PT J AU Ning, Y Laundon, CH Schrock, E Buchanan, P Ried, T AF Ning, Y Laundon, CH Schrock, E Buchanan, P Ried, T TI Prenatal diagnosis of a mosaic extra structurally abnormal chromosome by spectral karyotyping SO PRENATAL DIAGNOSIS LA English DT Article ID MARKER CHROMOSOMES AB A de novo mosaic extra structurally abnormal chromosome (ESAC) was detected in 33 per cent of cultured amniotic fluid cells from a pregnant woman. Neither Q-banding nor fluorescence in situ hybridization (FISH) employing a DNA probe for nucleolar organizer region demonstrated the presence of satellites on the ESAC. Spectral karyotyping (SKY) was performed in this prenatal case and led to a quick and accurate determination of the ESAC as chromosome 14 in origin. The SKY finding was confirmed by conventional FISH analysis using a chromosome 14 specific painting probe. Subsequent hybridizations with a centromeric probe and a 14q subtelomeric probe were also performed to further characterize the ESAC. Absence of (TTAGGG)n sequence on the ESAC, determined postnatally, suggested it is a ring chromosome 14. Genetic counselling concerning these findings was provided to the parents who chose to continue the pregnancy. The male infant had no apparent abnormal phenotype at birth. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 Gene Care Med Genet Ctr, Washington, DC 20037 USA. George Washington Univ, Washington, DC 20037 USA. Gene Care Med Genet Ctr, Chapel Hill, NC 27514 USA. NIH, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. RP Ning, Y (reprint author), Gene Care Med Genet Ctr, 2300 I St NW,Ross Hall,Rm 455, Washington, DC 20037 USA. NR 8 TC 15 Z9 16 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD MAY PY 1999 VL 19 IS 5 BP 480 EP 482 DI 10.1002/(SICI)1097-0223(199905)19:5<480::AID-PD547>3.3.CO;2-8 PG 3 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA 198PV UT WOS:000080433900015 PM 10360520 ER PT J AU Katz, SI AF Katz, SI TI Thematic review series VI: Skin gene therapy - Introduction SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Editorial Material C1 NIAMSD, NIH, Bethesda, MD 20892 USA. RP Katz, SI (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD MAY-JUN PY 1999 VL 111 IS 3 BP 183 EP 183 DI 10.1046/j.1525-1381.1999.99200.x PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 196YT UT WOS:000080338400001 ER PT J AU Vogel, JC AF Vogel, JC TI A direct in vivo approach for skin gene therapy SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Review DE cytokines; DNA vaccination; epidermis; genetic immunization; keratinocytes; plasmid DNA ID EPIDERMAL-KERATINOCYTES; NAKED DNA; EXPRESSION; IMMUNIZATION; CELLS; INJECTION; INDUCTION; CAVEOLAE; DELIVERY; GROWTH AB In vivo gene therapy is a direct and effective way to express genes in the epidermis. Plasmid DNA that contains the desired gene can be injected intradermally, and it is rapidly absorbed and expressed by the epidermis. Because gene expression following plasmid injection is transient, the two principal therapeutic uses of this approach are genetic immunization and the expression of biological response modifiers to treat skin disease. C1 NCI, NIH, Dermatol Branch, Bethesda, MD 20892 USA. RP Vogel, JC (reprint author), NCI, NIH, Dermatol Branch, Bldg 10,Room 12 N26,10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA. NR 27 TC 16 Z9 16 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD MAY-JUN PY 1999 VL 111 IS 3 BP 190 EP 197 DI 10.1046/j.1525-1381.1999.99223.x PG 8 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 196YT UT WOS:000080338400003 PM 10354358 ER PT J AU Ernst, M AF Ernst, M TI PET in child psychiatry: The risks and benefits of studying normal healthy children SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE children; ethical issues; positron emission tomography; minimal risk; radiation exposure ID POSITRON EMISSION TOMOGRAPHY; HUMAN-BRAIN; MATURATION AB 1. Inclusion of children, particularly healthy control children, is a continuing debate. 2. Why involve children in PET research? The assumption is that the knowledge gained from such studies is critical for the advance of prevention and treatment of psychiatric illnesses. 3. What are the risks of PET procedures? Radiation exposure poses the most difficult problem. The assessment of this risk needs to separate the emotional reaction at the mention of "radiation" from the consideration of objective data of large studies of health hazards associated with low-level radiation exposure. 4. The assessment of the benefit/risk ratio is critical to the conduct of research, and requires the evaluation of risks according to the ambiguous definition of "minimal risk". C1 NIDA, Brain Imaging Ctr, NIH, Baltimore, MD 21224 USA. RP Ernst, M (reprint author), NIDA, Brain Imaging Ctr, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 20 TC 12 Z9 12 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD MAY PY 1999 VL 23 IS 4 BP 561 EP 570 DI 10.1016/S0278-5846(99)00016-0 PG 10 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 200XB UT WOS:000080564500002 PM 10390716 ER PT J AU Giedd, JN Blumenthal, J Jeffries, NO Rajapakse, JC Vaituzis, AC Liu, H Berry, YC Tobin, M Nelson, J Castellanos, FX AF Giedd, JN Blumenthal, J Jeffries, NO Rajapakse, JC Vaituzis, AC Liu, H Berry, YC Tobin, M Nelson, J Castellanos, FX TI Development of the human corpus callosum during childhood and adolescence: A longitudinal MRI study SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE adolescent; brain; child; sex ID DEFICIT-HYPERACTIVITY DISORDER; SEXUAL DIMORPHISM; CHRONIC-SCHIZOPHRENIA; MORPHOMETRIC ANALYSIS; BRAIN; MORPHOLOGY; COMMISSUROTOMY; CONNECTIONS; CONTROVERSY; CHILDREN AB 1. Interest in the morphologic development of the corpus callosum (CC) during childhood and adolescence stems from adolescent changes in cognitive functions subserved by the CC, reports of CC anomalies for a wide variety of childhood neuropsychiatric illnesses, and controversy regarding sexual dimorphism. 2. Characterization of the normal developmental pattern of the CC is hindered by enormous variability of its size. This is especially problematic for cross-sectional studies seeking to assess possible nonlinear developmental curves. 3. To more accurately characterize developmental changes, a longitudinal brain magnetic resonance imaging study with subjects rescanned at approximately 2 year intervals was conducted resulting in 251 scans from 139 healthy children and adolescents. 4. Midsagittal area of the CC, especially the posterior regions, increased robustly from ages 5 to 18 years. 5. Although the genu of the CC was significantly larger in males there were no sex differences in mean area after adjustment for total cerebral volume and the growth patterns did not differ between sexes. 6. Analysis revealed a non-linear increase in the splenium, the most posterior region, with increases greatest in the younger years. 7. The results of this longitudinal study, in addition to confirming and extending previous cross-sectional reports, provide an increasingly accurate yardstick from which to assess pathological development. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Giedd, JN (reprint author), NIMH, Child Psychiat Branch, Bldg 10,Room 4C110,10 Ctr Dr,MSC 1367, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Rajapakse, Jagath/B-8485-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Rajapakse, Jagath/0000-0001-7944-1658; Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 61 TC 223 Z9 231 U1 2 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD MAY PY 1999 VL 23 IS 4 BP 571 EP 588 PG 18 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 200XB UT WOS:000080564500003 PM 10390717 ER PT J AU Djouadi, F Brandt, JM Weinheimer, CJ Leone, TC Gonzalez, FJ Kelly, DP AF Djouadi, F Brandt, JM Weinheimer, CJ Leone, TC Gonzalez, FJ Kelly, DP TI The role of the peroxisome proliferator-activated receptor alpha (PPAR alpha) in the control of cardiac lipid metabolism SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID ACYL-COA DEHYDROGENASE; FATTY-ACID OXIDATION; ENZYME GENE-EXPRESSION; SUDDEN CHILD-DEATH; TRANSCRIPTION FACTORS; MICE; RAT; FAILURE; ELEMENT; IDENTIFICATION AB The postnatal mammalian heart uses mitochondrial fatty acid oxidation (FAO) as the chief source of energy to meet the high energy demands necessary for pump function. Flux through the cardiac FAO pathway is tightly controlled in accordance with energy demands dictated by diverse physiologic and dietary conditions. in this report, we demonstrate that the lipid-activated nuclear receptor, peroxisome proliferator-activated receptor alpha (PPAR alpha), regulates the expression of several key enzymes involved in cardiac mitochondrial FAO. In response to the metabolic stress imposed by pharmacologic inhibition of mitochondrial long-chain fatty acid import with etomoxir, PPARa serves as a molecular 'lipostat' factor by inducing the expression of target genes involved in fatty acid utilization including enzymes involved in mitochondrial and peroxisomal beta-oxidation pathways. In mice lacking PPAR alpha (PPAR alpha-/- mice), etomoxir precipitates a cardiac phenotype characterized by myocyte lipid accumulation. Surprisingly, this metabolic regulatory response is influenced by gender as demonstrated by the observation that male PPAR alpha-/- mice are more susceptible to the metabolic stress compared to female animals. These results identify an important role for PPAR alpha in the control of cardiac lipid metabolism. C1 Washington Univ, Sch Med, Cardiovasc Res Ctr, Dept Pediat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Cardiovasc Res Ctr, Dept Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Cardiovasc Res Ctr, Dept Mol Biol & Pharmacol, St Louis, MO 63110 USA. Univ Paris 07, INSERM, U319, Paris, France. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Kelly, DP (reprint author), Washington Univ, Sch Med, Cardiovasc Res Ctr, Dept Pediat, 660 S Euclid Ave,Campus Box 8086, St Louis, MO 63110 USA. FU NHLBI NIH HHS [1 F32 HL09799-01]; NIDDK NIH HHS [DK 45416] NR 28 TC 93 Z9 95 U1 0 U2 5 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 MAY-JUN PY 1999 VL 60 IS 5-6 BP 339 EP 343 DI 10.1016/S0952-3278(99)80009-X PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 226FF UT WOS:000082009100009 PM 10471118 ER PT J AU Salem, N Pawlosky, R Wegher, B Hibbeln, J AF Salem, N Pawlosky, R Wegher, B Hibbeln, J TI In vivo conversion of linoleic acid to arachidonic acid in human adults SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID METABOLISM; INFANTS; TERM AB Human adults are shown to be capable of conversion of linoleic acid (LA, 18.2 n-6) to arachidonic acid (AA, 20:4 n-6) in vivo. It is confirmed that they can also convert alpha-linolenic acid (LNA, 18:3 n-3) to eicosapentaenoic acid (EPA, 20:5 n-3) and to docosahexaenoic acid (DHA, 22:6 n-3) in vivo. The time course and the maximal response for these processes during the first week after a single dose of the 18-carbon precursor is described. A stable-isotope method in which the protons of the C17 and C18 carbons are substituted with deuterium atoms is used in order to provide for a safe method for the study of human metabolism. High sensitivity and selectivity of detection is assured with negative ion, gas chromatography/mass spectrometry analysis. It is clear that human adults on an ad lib diet carry out EFA metabolism in vivo. C1 NIAAA, Rockville, MD 20852 USA. NIH, Bethesda, MD 20892 USA. RP Salem, N (reprint author), 12420 Parklawn Dr,Room 158, Rockville, MD 20852 USA. NR 12 TC 60 Z9 61 U1 2 U2 12 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 MAY-JUN PY 1999 VL 60 IS 5-6 BP 407 EP 410 DI 10.1016/S0952-3278(99)80021-0 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 226FF UT WOS:000082009100021 PM 10471130 ER PT J AU Turkkan, JS Shurtleff, D AF Turkkan, JS Shurtleff, D TI Cognitive sciences research: More than thinking about drug abuse SO PSYCHOLOGICAL SCIENCE LA English DT Article; Proceedings Paper CT Conference on Cognitive Sciences Research - More Than Thinking About Drug Abuse CY MAY 23, 1997 CL BETHESDA, MARYLAND SP NIDA, Amer Psychol Soc AB On May 23, 1997, the National institute on Drug Abuse and the American Psychological Society co-sponsored a conference titled "Cognitive Sciences Research: More Than Thinking About Drug Abuse." The conference highlighted important lines of research, both within and outside of drug abuse, that may elucidate the relationships between substance abuse and cognitive processes. This Special Section of Psychological Science presents a compilation of articles from that conference by scientists who are working in the forefront of this exciting new research area. The research questions posed by these articles take the following forms: What are the cognitive and developmental effects (i.e., the consequences) of substance abuse? What are the antecedents ai precursors of drug use that render persons vulnerable to taking drugs? How do the effects of drugs, in turn, become antecedents for changes in perception behavior and cognition that further enhance vulnerability to drugs?. C1 Natl Inst Drug Abuse, Behav Sci Res Branch, Bethesda, MD 20892 USA. RP Turkkan, JS (reprint author), Natl Inst Drug Abuse, Behav Sci Res Branch, 6001 Execut Blvd,Room 4282, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHERS PI MALDEN PA 350 MAIN STREET, STE 6, MALDEN, MA 02148 USA SN 0956-7976 J9 PSYCHOL SCI JI Psychol. Sci. PD MAY PY 1999 VL 10 IS 3 BP 179 EP 180 DI 10.1111/1467-9280.00129 PG 2 WC Psychology, Multidisciplinary SC Psychology GA 203YK UT WOS:000080735600001 ER PT J AU Schmidt, LA Fox, NA Goldberg, MC Smith, CC Schulkin, J AF Schmidt, LA Fox, NA Goldberg, MC Smith, CC Schulkin, J TI Effects of acute prednisone administration on memory, attention and emotion in healthy human adults SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE attention; emotion; frontal EEG asymmetry; glucocorticoids; memory; mood; prednisone; startle eyeblink response ID FEAR-POTENTIATED STARTLE; RHESUS-MONKEYS; NEUROENDOCRINE RESPONSES; INDIVIDUAL-DIFFERENCES; BEHAVIORAL-INHIBITION; SOCIAL COMPETENCE; SAMPLE-SIZE; CORTISOL; ASYMMETRY; CORTICOSTEROIDS AB We conducted a double-blind study in order to examine the effects of high doses of prednisone on memory, attention and emotion in humans. A total of 24 healthy undergraduate males self-administered either 160 mg of prednisone (n = 12) or a placebo (n = 12) for 4 consecutive days. We examined group differences in mood, regional brain electrical activity (EEG), the startle eyeblink response, memory recall and performance on an attention task after 4 days of treatment. We found significant group differences on measures of mood and frontal EEG alpha activity on 4-day treatment. Subjects treated with prednisone exhibited a significantly greater increase in self-reported negative emotion and greater relative right frontal EEG alpha activity on 4-day treatment compared with adults in the placebo group. We also found that subjects treated with prednisone recalled fewer objects on the memory task following treatment. No significant group differences were found on posterior EEG activity, the startle eyeblink measure, or the attention measure. These findings suggest that administration of high doses of exogenous prednisone may facilitate the experience of negative emotion and shifts in frontal EEG activity, and impair some aspects of cognitive functioning in humans. The multiple roles of glucocorticoids in memory, attention and emotion are discussed. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 McMaster Univ, Dept Psychol, Hamilton, ON L8S 4K1, Canada. Univ Maryland, Inst Child Study, College Pk, MD 20742 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. NIMH, Neuroendocrine Immunol & Behav Unit, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. NIMH, Behav Neurosci Unit, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. RP Schmidt, LA (reprint author), McMaster Univ, Dept Psychol, 1280 Main St W, Hamilton, ON L8S 4K1, Canada. EM schmidtl@mcmaster.ca FU NICHD NIH HHS [HD 17899] NR 68 TC 70 Z9 71 U1 3 U2 6 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 MAY PY 1999 VL 24 IS 4 BP 461 EP 483 DI 10.1016/S0306-4530(99)00007-4 PG 23 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 187AC UT WOS:000079762900007 PM 10341371 ER PT J AU Buczek, Y Le, AD Wang, A Stewart, J Shaham, Y AF Buczek, Y Le, AD Wang, A Stewart, J Shaham, Y TI Stress reinstates nicotine seeking but not sucrose solution seeking in rats SO PSYCHOPHARMACOLOGY LA English DT Article DE drug self-administration; extinction; nicotine; reinstatement; relapse; stress; sucrose ID CORTICOTROPIN-RELEASING-FACTOR; DISCRIMINATIVE STIMULUS; MOLECULAR MECHANISMS; INDUCED RELAPSE; HEROIN-SEEKING; DRUG-SEEKING; BEHAVIOR; ADDICTION; COCAINE; SENSITIZATION AB Rationale: Intermittent footshock stress effectively reinstates extinguished heroin-, cocaine- and alcohol-taking behaviors, but not behaviors previously maintained by food reinforcers. Here we tested further the generality of the phenomenon of stress-induced reinstatement by determining the effect of footshock on reinstatement of operant responding previously maintained by nicotine or palatable sucrose solutions. Methods: Groups of rats were trained to self-administer either nicotine (0.03 mg/kg per infusion, 14 days) or sucrose (10 or 30% w/v, 14-20 days). After extinction of the nicotine- or the sucrose-reinforced behaviors for 5-15 days, the rats were exposed to intermittent footshock stress (5 and 15 min, 0.8 mA) during tests for reinstatement. Results: Footshock reliably reinstated nicotine seeking after extinction of the drug-reinforced behavior. In contrast, the same parameters of footshock stress did not consistently reinstate operant responding previously maintained by sucrose solutions. Conclusions: These and previous data suggest that stressors may be more effective stimuli for reinstatement of behaviors previously maintained by drug reinforcers as compared with non-drug reinforcers. C1 NIDA, Dept Behav Neurosci, IRP, NIH, Baltimore, MD 21224 USA. Univ Toronto, Dept Pharmacol, Toronto, ON, Canada. Concordia Univ, Dept Psychol, Ctr Studies Behav Neurobiol, Montreal, PQ, Canada. RP Shaham, Y (reprint author), NIDA, Dept Behav Neurosci, IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI shaham, yavin/G-1306-2014 NR 37 TC 128 Z9 131 U1 1 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAY PY 1999 VL 144 IS 2 BP 183 EP 188 DI 10.1007/s002130050992 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 203LH UT WOS:000080708800011 PM 10395000 ER PT J AU Jacob, RG Thayer, JF Manuck, SB Muldoon, MF Tamres, LK Williams, DM Ding, Y Gatsonis, C AF Jacob, RG Thayer, JF Manuck, SB Muldoon, MF Tamres, LK Williams, DM Ding, Y Gatsonis, C TI Ambulatory blood pressure responses and the circumplex model of mood: A 4-day study SO PSYCHOSOMATIC MEDICINE LA English DT Article DE ambulatory blood pressure; ambulatory heart rate; ambulatory mood; circumplex mood model ID HEART-RATE; CARDIOVASCULAR REACTIVITY; STRESS; HYPERTENSIVES; EXERCISE; STATES; SLEEP; WORK; EMOTION; RHYTHM AB Background: The relation between mood or emotions and concurrent ambulatory blood pressure responses holds both fundamental and clinical interest. Methods: The primary sample consisted of 69 normotensive or borderline hypertensive but otherwise healthy adult males. The validation sample consisted of 85 healthy male undergraduate college students. Both samples underwent half-hourly 24-hour ambulatory blood pressure measurements on four separate workdays, 1 week apart. At each ambulatory measurement, subjects recorded their behavior, environment, and mood. The circular mood scale, a circular visual analogue scale based on the circumplex model of mood, was used to reflect the totality of a participant's affective state space. Longitudinal random effects regression models were applied in the data analysis. Results: The results for both samples were quite similar. Sleep and posture had the greatest influence on ambulatory blood pressure and heart rate. The effects of the environmental setting, social setting, and consumption were modest but statistically significant. Independent of these covariates, mood exerted a significant effect on blood pressure and heart rate. Relative to the "mellow" default category, blood pressure increased both for "anxious/annoyed" and "elated/happy" and decreased during "disengaged/sleepy" mood. The range of mood-related blood pressure estimates was 6.0/3.7 mm Hg. Conclusions: The pattern of blood pressure responses suggests that they were related to the degree of engagement of a mood rather than the degree of unpleasantness. The hypothesis that posits that negative affect-related cardiovascular reactivity mediates the observed correlation between negative affect and disease risk should be reconsidered. C1 Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15213 USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA. RP Jacob, RG (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, 3811 OHara St, Pittsburgh, PA 15213 USA. FU NHLBI NIH HHS [HL49062] NR 56 TC 23 Z9 24 U1 4 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD MAY-JUN PY 1999 VL 61 IS 3 BP 319 EP 333 PG 15 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 199HF UT WOS:000080474600011 PM 10367612 ER PT J AU Robbins, JB Schneerson, R Szu, SC Pozsgay, V AF Robbins, JB Schneerson, R Szu, SC Pozsgay, V TI Bacterial polysaccharide-protein conjugate vaccines SO PURE AND APPLIED CHEMISTRY LA English DT Article; Proceedings Paper CT 19th International Carbohydrate Symposium CY AUG 09-14, 1998 CL SAN DIEGO, CALIFORNIA ID INFLUENZAE TYPE-B; VI-CAPSULAR POLYSACCHARIDE; SHIGELLA-DYSENTERIAE TYPE-1; O-SPECIFIC POLYSACCHARIDE; ANTIBODY-RESPONSE; SERUM ANTIBODIES; IMMUNOLOGICAL PROPERTIES; NEISSERIA-MENINGITIDIS; SYSTEMIC INFECTIONS; SALMONELLA-TYPHI AB The age-related and T-cell independent properties of polysaccharides limit their use as vaccines. These limitations are overcome by covalently binding polysaccharides to proteins to form conjugates. Widespread use of Haemophilus influenzae type b (Hib) conjugates has virtually eliminated systemic infection caused by this pathogen, notably meningitis, in individuals of all ages. The principles derived from the development and use of Hib conjugates have been applied to other capsulated pathogens including pneumococci and meningococci. We have shown that vaccine-induced serum IgG antibodies to the surface polysaccharides of enteric pathogens confer immunity to typhoid fever (Vi) and to S. sonnei. Our preliminary data show that synthetic saccharides provide a method for increasing the immunogenicity of conjugates and permitted more direct characterization of a S. dysenteriae type 1 conjugate. Both the chain length and density of the saccharides on the protein were related to the immunogenicity of conjugates in mice. A synthetic approach has also been extended to the LPS types of Vibrio cholerae O1. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Robbins, JB (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. NR 53 TC 22 Z9 22 U1 1 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0033-4545 J9 PURE APPL CHEM JI Pure Appl. Chem. PD MAY PY 1999 VL 71 IS 5 BP 745 EP 754 DI 10.1351/pac199971050745 PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA 241HY UT WOS:000082877900004 ER PT J AU Parry, DAD Steinert, PM AF Parry, DAD Steinert, PM TI Intermediate filaments: molecular architecture, assembly, dynamics and polymorphism SO QUARTERLY REVIEWS OF BIOPHYSICS LA English DT Review ID FIBRILLARY ACIDIC PROTEIN; HELICAL COILED COILS; HARD ALPHA-KERATIN; TRANSMISSION ELECTRON-MICROSCOPY; NEUROFILAMENT TRIPLET PROTEINS; EPIDERMOLYSIS-BULLOSA SIMPLEX; S-CARBOXYMETHYLKERATIN-A; CORNIFIED CELL ENVELOPES; BOVINE EPIDERMAL KERATIN; DROSOPHILA LAMIN DM(0) C1 Massey Univ, Inst Fundamental Sci, Palmerston North, New Zealand. NIAMSD, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. RP Parry, DAD (reprint author), Massey Univ, Inst Fundamental Sci, Private Bag 11-222, Palmerston North, New Zealand. NR 277 TC 153 Z9 161 U1 1 U2 9 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0033-5835 J9 Q REV BIOPHYS JI Q. Rev. Biophys. PD MAY PY 1999 VL 32 IS 2 BP 99 EP 187 DI 10.1017/S0033583500003516 PG 89 WC Biophysics SC Biophysics GA 320NX UT WOS:000087408200001 PM 10845237 ER PT J AU Vymazal, J Righini, A Brooks, RA Canesi, M Mariani, C Leonardi, M Pezzoli, G AF Vymazal, J Righini, A Brooks, RA Canesi, M Mariani, C Leonardi, M Pezzoli, G TI T1 and T2 in the brain of healthy subjects, patients with Parkinson disease, and patients with multiple system atrophy: Relation to iron content SO RADIOLOGY LA English DT Article DE brain, iron; brain, MR; Parkinson disease; multiple system atrophy ID DIFFERENT FIELD STRENGTHS; BASAL GANGLIA; FERRITIN; HYPOTHESIS; MRI; TIME AB PURPOSE: To investigate the potential of magnetic resonance imaging for identification and quantification of brain iron in healthy subjects, patients with Parkinson disease, and patients with multiple system atrophy. MATERIALS AND METHODS: Forty-nine subjects were studied at 1.5 T. Regional T1 and T2 values were compared among groups and also with histopathologic estimates of iron concentration. RESULTS: In healthy subjects, interregional T1 and T2 differences in the cortex and basal ganglia showed a good correlation with reported values for iron concentration, and intraregional variations were generally consistent with reported variability of iron concentration. Patients with multiple system atrophy had Tl and T2 shortening in the globus pallidus consistent with reported increases in ferritin-bound iron and changes in the putamen consistent with accumulation df hemosiderin (posterior portion);and neuromelanin (remainder). Both groups of-patients had changes in the cortex that are consistent-with decreased ferritin concentration and T2 changes in white matter consistent with demyelination. Patients with Parkinson disease also had a (nonsignificant) T2 shortening in the substantia nigra that was suggestive of iron accumulation. CONCLUSION: Most of the T1 and T2 findings appear to be related to changes in iron content and form and may possibly be used as indicators of such changes. C1 Osped Maggiore Policlin, IRCCS, Dept Neuroradiol, Milan, Italy. Ist Clin Perfezionamento, Ctr Parkinsons Dis, Milan, Italy. NINDS, Neuroimaging Branch, NIH, Bethesda, MD 20892 USA. RP Hosp Holmolce, Dept Stereotact & Radiat Neurosurg, Prague 15119, Czech Republic. NR 31 TC 193 Z9 201 U1 2 U2 11 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 1999 VL 211 IS 2 BP 489 EP 495 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 189WM UT WOS:000079929200028 PM 10228533 ER PT J AU Bernard, M Guerlotte, J Greve, P Grechez-Cassiau, A Iuvone, MP Zatz, M Chong, NW Klein, DC Voisin, P AF Bernard, M Guerlotte, J Greve, P Grechez-Cassiau, A Iuvone, MP Zatz, M Chong, NW Klein, DC Voisin, P TI Melatonin synthesis pathway: circadian regulation of the genes encoding the key enzymes in the chicken pineal gland and retina SO REPRODUCTION NUTRITION DEVELOPMENT LA English DT Article; Proceedings Paper CT 8th Meeting of the European-Pineal-Society CY JUL 03-07, 1999 CL TOURS, FRANCE SP European Pineal Soc DE melatonin; tryptophan hydroxylase; arylalkylamine N-acetyltransferase hydroxyindole-O-methyltransferase; pineal; retina ID HYDROXYINDOLE-O-METHYLTRANSFERASE; SEROTONIN N-ACETYLTRANSFERASE; MESSENGER-RNA LEVELS; TRYPTOPHAN-HYDROXYLASE; HOMEOBOX GENE; CLOCK; PHOTORECEPTOR; CELLS; RHYTHM; EXPRESSION AB The mRNAs encoding three enzymes of the melatonin synthesis pathway (tryptophan hydroxylase (TPH), arylalkylamine-N-acetyltransferase (AANAT) and hydroxyindole-O-methyltransferase (HIOMT)) are expressed with a day/night rhythm in the chicken pineal gland and retina. TPH and AANAT mRNA levels reach their peak at night. HIOMT mRNA levels peak at night in the retina, but during the day in the pineal gland. In this tissue, the rhythm of TPH, AANAT and HIOMT mRNA levels persisted in constant darkness (DD), both in vivo and in vitro, indicating that the three genes are controlled by the circadian oscillator of the chicken pineal. In the retina, the rhythms of TPH and AANAT mRNA levels also persisted in DD in vivo, suggesting that they are driven by a circadian oscillator. In contrast, the rhythm of HIOMT mRNA in the retina appeared to be controlled only by light. The clones of chicken AANAT and HIOMT genes that we have isolated should help us to understand the molecular mechanisms of: 1) their transcriptional regulation by circadian oscillators and by light; 2) their tissue-specific expression in the pineal gland and the retina. (C) Inra/Elsevier, Paris. C1 CNRS, UMR 6558, Neuroendocrinol Lab, F-86022 Poitiers, France. Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA. NIMH, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. NICHHD, Sect Neuroendocrinol, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Bernard, M (reprint author), CNRS, UMR 6558, Neuroendocrinol Lab, 40 Ave Recteur Pineau, F-86022 Poitiers, France. NR 44 TC 40 Z9 40 U1 1 U2 8 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0926-5287 J9 REPROD NUTR DEV JI Reprod. Nutr. Dev. PD MAY-JUN PY 1999 VL 39 IS 3 BP 325 EP 334 DI 10.1051/rnd:19990305 PG 10 WC Developmental Biology; Nutrition & Dietetics; Reproductive Biology; Zoology SC Developmental Biology; Nutrition & Dietetics; Reproductive Biology; Zoology GA 211WK UT WOS:000081184700006 PM 10420435 ER PT J AU Foley, DJ Monjan, AA Izmirlian, G Hays, JC Blazer, DG AF Foley, DJ Monjan, AA Izmirlian, G Hays, JC Blazer, DG TI Incidence and remission of insomnia among elderly adults in a biracial cohort SO SLEEP LA English DT Article DE aging; longitudinal; depression; epidemiology; race ID SLEEP COMPLAINTS; ESTABLISHED POPULATIONS; OLDER ADULTS; PREVALENCE; COMMUNITY; HEALTH; DISTURBANCES; DISORDERS AB Objectives: To determine the incidence and remission rates of insomnia in older adults according to race and associated risk factors in a three-year longitudinal study. Methods: 2,971 men and women, aged 65 years and older, completed questionnaires administered by trained interviewers at baseline and three years later. Data concerning difficulty falling asleep or early morning arousal (insomnia), along with self-reports of physical disability, respiratory symptoms, depressive symptomatology, perceived health status, and use of prescribed sedative medication, were collected and analyzed. Results: Overall, 15% of the participants without symptoms of insomnia at baseline reported chronic difficulty falling asleep or early morning arousal three years later in follow-up interviews. African-American women had a significantly (p<0.01) higher incidence of insomnia (19%) compared with African-American men (12%) or with white men and women (both 14%). Men were more likely than women to no longer report symptoms at follow-up (64% vs 42%; p<0.01). For both races, the presence of depressed mood was a risk factor for the incidence of insomnia, and the absence of depressed mood was a predictor of remission. Conclusions: Insomnia occurs more frequently in African-American women than in African-American men or than in white men or women. Regardless of race, women are less likely than men to resolve their insomnia. The high prevalence and incidence of morbidity in elderly African-American women may contribute to their high rate of insomnia. C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. NIA, Neurosci & Neuropsychol Aging Program, Bethesda, MD 20892 USA. Duke Univ, Dept Psychiat, Durham, NC 27706 USA. RP Foley, DJ (reprint author), NIA, Epidemiol Demog & Biometry Program, Rm 3C-309 Bethesda Gateway Bldg,7201 Wisconsin Av, Bethesda, MD 20892 USA. FU NIA NIH HHS [AG-1-2102] NR 28 TC 50 Z9 51 U1 3 U2 4 PU AMER SLEEP DISORDERS ASSOC PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAY 1 PY 1999 VL 22 SU 2 BP S373 EP S378 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 227GA UT WOS:000082070000006 PM 10394610 ER PT J AU Foley, DJ Monjan, A Simonsick, EM Wallace, RB Blazer, DG AF Foley, DJ Monjan, A Simonsick, EM Wallace, RB Blazer, DG TI Incidence and remission of insomnia among elderly adults: An epidemiologic study of 6,800 persons over three years SO SLEEP LA English DT Article DE aging; insomnia; incidence; longitudina; depression; epidemiology ID ESTABLISHED POPULATIONS; SLEEP DISTURBANCES; COMPLAINTS; PREVALENCE; COMMUNITY; HEALTH AB To determine incidence and remission rates of insomnia in older adults and associated risk factors. Three-year longitudinal study, 1982-198-East Boston, MA; New Haven, CT; Iowa and Washington counties, IA. Participants were 6,899 men and women aged 65 years and older. Self reported difficulty falling asleep or early morning arousal (insomnia), along with physician diagnosis of heart disease, stroke, cancer, diabetes, or hip-fracture, self-report of physical disability, depressive symptomatology, perceived health status, and use of medications ascertained at both baseline and three-year follow-up. Nearly 15% of the 4,956 participants without symptoms of insomnia at baseline reported chronic difficulty falling asleep or early morning arousal at follow-up, suggesting an annual incidence rate of approximately 5%. Incident insomnia was associated with depressed mood, respiratory symptoms, fair to poor perceived health, and physical disability. In multivariate analyses, these risk factors explained the higher incidence of insomnia among those with medical conditions such as heart disease, stroke, and diabetes. Other factors associated with an increased risk of insomnia included use of prescribed sedatives, and widowhood. Only 7% of the incident cases of insomnia occurred in the absence of associated risk factors. Of the nearly 2,000 survivors with chronic insomnia at baseline, almost half no longer reported symptoms upon follow-up and were more likely to report improved self-peceived health compared to those who continued to report symptoms. Chronic disease, depressed mood, physical disability, poor perceived health, widowhood, and use of sedatives are associated with development and remission of insomnia symptoms. Because the vast majority of incident cases of insomnia were among persons with one or more of these risk factors, these data do not support a model of incident insomnia caused by the aging process per se. C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. NIA, Neurosci & Neuropsychol Aging Program, Bethesda, MD 20892 USA. Univ Iowa, Dept Prevent Med, Iowa City, IA 52242 USA. Duke Univ, Dept Psychiat, Durham, NC 27706 USA. RP Foley, DJ (reprint author), NIA, Epidemiol Demog & Biometry Program, Rm 3C-309 Bethesda Gateway Bldg,7201 Wisconsin Av, Bethesda, MD 20892 USA. NR 24 TC 167 Z9 169 U1 4 U2 20 PU AMER SLEEP DISORDERS ASSOC PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAY 1 PY 1999 VL 22 SU 2 BP S366 EP S372 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 227GA UT WOS:000082070000005 PM 10394609 ER PT J AU Kiley, JP AF Kiley, JP TI Insomnia research and future opportunities - Forward SO SLEEP LA English DT Editorial Material C1 NIH, Natl Ctr Sleep Disorders Res, Bethesda, MD 20892 USA. RP Kiley, JP (reprint author), NIH, Natl Ctr Sleep Disorders Res, Bethesda, MD 20892 USA. NR 1 TC 12 Z9 12 U1 0 U2 1 PU AMER SLEEP DISORDERS ASSOC PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAY 1 PY 1999 VL 22 SU 2 BP S344 EP S345 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 227GA UT WOS:000082070000001 PM 10394605 ER PT J CA Natl Ctr Sleep Disorders Res Natl Heart Lung Blood Inst Natl Inst Hlth TI Insomnia: Assessment and management in primary care SO SLEEP LA English DT Article ID DAYTIME SLEEPINESS; PSYCHIATRIC-DISORDERS; TREATMENT EFFICACY; COMPLAINTS; METAANALYSIS; POPULATION; PREVALENCE; TRIAZOLAM; TRAZODONE; ZOLPIDEM C1 St Lukes Hosp, Sleep Med & Res Ctr, Chesterfield, MO 63017 USA. Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA. VA Hosp, Sleep Disorders Lab, Dayton, OH USA. Western Psychiat Inst & Clin, Sleep & Chronobiol Ctr, Pittsburgh, PA USA. St Mary Hosp, Katherine Severyns Dement Sleep Disorder Ctr, Walla Walla, WA USA. Georgetown Univ, Med Ctr, Dept Family Med, Washington, DC 20007 USA. Mayo Clin, Mayo Sleep Disorders Ctr, Rochester, MN USA. Univ Laval, Ecole Psychol, Sleep Disorders Res Ctr, Ste Foy, PQ G1K 7P4, Canada. Henry Ford Hosp, Sleep Disorders Ctr, Detroit, MI 48202 USA. NHLBI, Natl Ctr Sleep Disorders Res, Bethesda, MD 20892 USA. NHLBI, Sleep Educ Act, Off Prevent Educ & Control, Bethesda, MD 20892 USA. NIA, Bethesda, MD 20892 USA. ROW Sci Inc, Rockville, MD USA. RP St Lukes Hosp, Sleep Med & Res Ctr, 232 S Woods Mill Rd, Chesterfield, MO 63017 USA. NR 34 TC 0 Z9 1 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD MAY 1 PY 1999 VL 22 SU 2 BP S402 EP S408 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 227GA UT WOS:000082070000010 ER PT J AU Xiao, B Shi, GB Chen, X Yan, HG Ji, XH AF Xiao, B Shi, GB Chen, X Yan, HG Ji, XH TI Crystal structure of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase, a potential target for the development of novel antimicrobial agents SO STRUCTURE WITH FOLDING & DESIGN LA English DT Article DE antimicrobial agent; drug design; HPPK; protein fold; pyrophosphoryl transfer ID DIFFRACTION DATA; PROTEIN; TRIMETHOPRIM; 7,8-DIHYDRO-6-HYDROXYMETHYLPTERIN-PYROPHOSPHOKINASE; SPECTROSCOPY; REFINEMENT; RESISTANCE; PROGRAM AB Background: Folate cofactors are essential for life. Mammals derive folates from their diet, whereas most microorganisms must synthesize folates de novo. Enzymes of the folate pathway therefore provide ideal targets for the development of antimicrobial agents, 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the transfer of pyrophosphate from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP), the first reaction in the folate biosynthetic pathway. Results: The crystal structure of HPPK from Escherichia coli has been determined at 1.5 Angstrom resolution with a crystallographic R factor of 0.182. The HPPK molecule has a novel three-layered alpha beta alpha fold that creates a valley approximately 26 Angstrom long, 10 Angstrom wide and 10 Angstrom deep, The active center of HPPK is located in the valley and the substrate-binding sites have been identified with the aid of NMR spectroscopy. The HP-binding site is located at one end of the valley, near Asn55, and is sandwiched between two aromatic sidechains. The ATP-binding site is located at the other end of the valley. The adenine base of ATP is positioned near Leu111 and the ribose and the triphosphate extend across and reach the vicinity of HP. Conclusions: The HPPK structure provides a framework to elucidate structure/function relationships of the enzyme and to analyze mechanisms of pyrophosphoryl transfer. Furthermore, this work may prove useful in the structure-based design of new antimicrobial agents. C1 Michigan State Univ, Dept Biochem, E Lansing, MI 48824 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Yan, HG (reprint author), Michigan State Univ, Dept Biochem, E Lansing, MI 48824 USA. RI Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 NR 32 TC 54 Z9 56 U1 1 U2 6 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0969-2126 J9 STRUCT FOLD DES JI Struct. Fold. Des. PD MAY PY 1999 VL 7 IS 5 BP 489 EP 496 DI 10.1016/S0969-2126(99)80065-3 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 201CL UT WOS:000080577000006 PM 10378268 ER PT J AU Costantini, M Musso, M Viterbori, P Bonci, F Del Mastro, L Garrone, O Venturini, M Morasso, G AF Costantini, M Musso, M Viterbori, P Bonci, F Del Mastro, L Garrone, O Venturini, M Morasso, G TI Detecting psychological distress in cancer patients: validity of the Italian version of the Hospital Anxiety and Depression Scale SO SUPPORTIVE CARE IN CANCER LA English DT Article DE cancer; anxiety; depression; hospital anxiety and depression scale psychological screening ID INFLAMMATORY BOWEL-DISEASE; ADJUSTMENT DISORDERS; VALIDATION; SYMPTOMS; TRIAL; HADS AB The psychometric properties of the Italian version of the Hospital Anxiety and Depression Scale and its utility as a screening instrument for anxiety and depression in a non-psychiatric setting were evaluated. The questionnaire was administered twice to 197 breast cancer patients randomised in a phase III adjuvant clinical trial: before the start of chemotherapy and at the first followup visit. The presence of psychiatric disorders was evaluated at the followup visit using the Structured Clinical Interview for DSM-III-R in 132 patients. Factor analyses identified two strictly correlated factors. Crohnbach's alpha for the anxiety and depression scales ranged between 0.80 and 0.85. At follow-up, 50 patients (38%) were assigned a current DSM-III-R diagnosis, in most cases adjustment disorders (24%) or major depressive disorder (10%). Receiver operating characteristics (ROC) analysis was used to test the discriminant validity for both anxiety and depressive disorders. The comparison of the areas under the curve (AUC) between the two scales did not show any difference in identifying either anxiety (P=0.855) or depressive disorders (P=0.357). The 14-item total scale showed a high internal consistency (alpha=0.89 and 0.88) and a high discriminating power for all the psychiatric disorders (AUC=0.89; 95% CI=0.83-0.94). The cut-off point that maximised sensitivity (84%) and specificity (79%) was 10. These results suggest that the total score is a valid measure of emotional distress, so that the Italian version of HADS can be used as a screening questionnaire for psychiatric disorders. The use of the two subscales as a 'case identifier' or as an outcome measure should be considered with caution. C1 Natl Canc Inst, Unit Clin Epidemiol & Trials, I-16132 Genoa, Italy. Natl Canc Inst, Dept Psychol, I-16132 Genoa, Italy. Natl Canc Inst, Dept Med Oncol 1, I-16132 Genoa, Italy. Dept Med Oncol, Pisa, Italy. RP Costantini, M (reprint author), Natl Canc Inst, Unit Clin Epidemiol & Trials, Lgo R Benzi 10, I-16132 Genoa, Italy. RI costantini, massimo/G-1443-2012; OI VITERBORI, PAOLA/0000-0002-0241-646X; costantini, massimo/0000-0002-5293-7079; Del Mastro, Lucia/0000-0002-9546-5841 NR 37 TC 171 Z9 172 U1 0 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0941-4355 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD MAY PY 1999 VL 7 IS 3 BP 121 EP 127 DI 10.1007/s005200050241 PG 7 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 189MF UT WOS:000079908300004 PM 10335929 ER PT J AU Heinz, A Saunders, RC Kolachana, BS Jones, DW Gorey, JG Bachevalier, J Weinberger, DR AF Heinz, A Saunders, RC Kolachana, BS Jones, DW Gorey, JG Bachevalier, J Weinberger, DR TI Striatal dopamine receptors and transporters in monkeys with neonatal temporal limbic damage SO SYNAPSE LA English DT Article DE prefrontal regulation; phasic dopamine release; neurodevelopmental hypothesis; IBZM SPECT; beta-CIT SPECT ID EXCITOTOXIC HIPPOCAMPAL DAMAGE; VENTRAL TEGMENTAL AREA; NUCLEUS-ACCUMBENS; PREFRONTAL CORTEX; NONHUMAN-PRIMATES; RELEASE; SCHIZOPHRENIA; AMPHETAMINE; NEURONS; BRAIN AB Developmental cortical damage has been implicated in the basic neurobiology of schizophrenia. Adult rhesus monkeys with neonatal temporal limbic damage show a stimulus-dependent disinhibition of subcortical dopamine (DA) release. We measured dopamine D2 receptors and transporters in vivo in rhesus monkeys with neonatal and adult mesial temporal limbic lesions and control monkeys to explore further the effects of this developmental lesion on striatal DA function. All monkeys were studied with [I-123]IBZM SPECT to assess the availability of striatal dopamine D2 receptors and with [I-123]beta-CIT SPECT to measure the availability of dopamine transporters in the striatum. IBZM binding was significantly reduced in monkeys with neonatal limbic lesions. No group difference in beta-CIT binding was found. The reduction in IBZM binding was significantly correlated with subcortical dopamine release after monoaminergic prefrontal stimulation as determinated with in vivo microdialysis. Our findings imply specific interactions between age at lesion and the availability of DA transporter and receptors in non-human primates, and suggest that stimulus-dependent DA activity affects the expression of DA receptors. Synapse 31:71-79, 1999. Published 1999 Wiley-Liss, Inc.dagger. C1 NIMH, Clin Brain Disorders Branch, Intramural Res Program, Bethesda, MD 20892 USA. RP Weinberger, DR (reprint author), NIMH, Clin Brain Disorders Branch, Intramural Res Program, Bethesda, MD 20892 USA. EM weinberg@dirpc.nimh.nih.gov NR 42 TC 45 Z9 45 U1 3 U2 3 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 MAY PY 1999 VL 32 IS 2 BP 71 EP 79 DI 10.1002/(SICI)1098-2396(199905)32:2<71::AID-SYN1>3.0.CO;2-Q PG 9 WC Neurosciences SC Neurosciences & Neurology GA 183DX UT WOS:000079539700001 PM 10231127 ER PT J AU Robbins, J AF Robbins, J TI Pharmacology of bovine and human thyrotropin: An historical perspective SO THYROID LA English DT Article; Proceedings Paper CT Recombinant Human Thyrotropin Symposium CY SEP 16, 1998 CL PORTLAND, OREGON AB Before the induction of a brief period of hypothyroidism became the standard method for inducing I-131 uptake in thyroid cancer diagnosis and therapy, several other methods were explored and used. At the dawn of this new era of recombinant human thyrotropin (TSH) it is of interest to reflect briefly on some of this work. Partially purified bovine TSH (bTSH) was supplied for many years by the Armour Company as Thytropar for intramuscular injection and was first used in thyroid cancer 50 years ago at the Montefiore Hospital and at the Memorial Sloan Kettering Cancer Center in New York City. Most of the patients were already hypothyroid and bTSH induced further I-131 uptake in only a few. Experience over the next 30 years revealed frequent allergic reactions, occasionally serious ones, and in 1961 it was shown that prolonged use could result in resistance to both bTSH and human TSH. bTSH was, therefore, reserved for thyroid cancer patients unable to increase endogenous TSH when hypothyroid. bTSH also was used widely as a test to distinguish between hypothyroidism caused by thyroid or pituitary failure until it was replaced by thyrotropin-releasing hormone (TRH). In a few studies, TRH was also tested as an adjuvant to increase endogenous TSH and thus help to stimulate function in thyroid cancer, but this attracted little interest. Prolonged hypothyroidism, enhanced by antithyroid drugs, was used early on, but this very effective stimulant of thyroid cancer function was, for multiple reasons, discarded. Beginning interest 15 to 25 years ago in obtaining TSH from human pituitary glands, a byproduct of growth hormone production, was interrupted when this product was found to risk development of Creutzfeld-Jakob disease. Recombinant human TSH, a safe and effective substitute, is now ready for widespread use and development in thyroid cancer management. C1 NIH, Dept Hlth & Human Serv, Genet & Biochem Branch, Bethesda, MD 20892 USA. RP Robbins, J (reprint author), NIH, Dept Hlth & Human Serv, Genet & Biochem Branch, Bldg 10,Room 6C 201A,10 Ctr Dr,MSC 1587, Bethesda, MD 20892 USA. NR 13 TC 19 Z9 19 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 MAY PY 1999 VL 9 IS 5 BP 451 EP 453 DI 10.1089/thy.1999.9.451 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 200AA UT WOS:000080515200007 PM 10365676 ER PT J AU Boorman, GA McCormick, DL Findlay, JC Hailey, JR Gauger, JR Johnson, TR Kovatch, RM Sills, RC Haseman, JK AF Boorman, GA McCormick, DL Findlay, JC Hailey, JR Gauger, JR Johnson, TR Kovatch, RM Sills, RC Haseman, JK TI Chronic toxicity oncogenicity evaluation of 60 Hz (power frequency) magnetic fields in F344/N rats SO TOXICOLOGIC PATHOLOGY LA English DT Article DE rodent carcinogenicity studies; electromagnetic fields; extremely low frequency (ELF); alternating fields; cancer; bio-assay; thyroid C-cell tumors ID ELECTRIC UTILITY WORKERS; MEDULLARY THYROID-CARCINOMA; ELECTROMAGNETIC-FIELDS; OCCUPATIONAL EXPOSURE; WIRING CONFIGURATIONS; CHILDHOOD-CANCER; DIET NTP-2000; LEUKEMIA; CARCINOGENICITY; CHILDREN AB A 2-yr whole-body exposure study was conducted to evaluate the chronic toxicity and possible oncogenicity of 60 Hz (power frequency) magnetic fields in rats. Groups of 100 male and 100 female F344/N rats were exposed continuously to pure, linearly polarized, transient-free 60 Hz magnetic fields at flux densities of 0 Gauss (G) (sham control), 20 milligauss (mG), 2 G, and 10 G; an additional group of 100 male and 100 female F344/N rats received intermittent (1 hr on/1 hr off) exposure to 10 G fields. Mortality patterns, body weight,gains throughout the study, and the total incidence and number of malignant and benign tumors in all groups exposed to magnetic fields were similar to those found in sex-matched sham controls. Statistically significant increases in the combined incidence of C-cell adenomas and carcinomas of the thyroid were seen in male rats chronically exposed to 20 mG and 2 G magnetic fields. These increases were not seen in male rats exposed continuously or intermittently to 10 G fields or in female rats at any magnetic field exposure level. No increases in the incidence of neoplasms, which have been identified in epidemiology studies as possible targets of magnetic field action (leukemia, breast cancer, and brain cancer), were found in any group exposed to magnetic fields. There was a decrease in leukemia in male rats exposed to 10 G intermittent fields. The occurrence of C-cell tumors at the 2 lower field intensities in male rats is interpreted as equivocal evidence of carcinogenicity; data from female rats provides no evidence of carcinogenicity in that sex. These data, when considered as a whole, are interpreted as indicating that chronic exposure to pure linearly polarized 60 Hz magnetic fields has little or no effect on cancer development in the F344/N rat. C1 NIEHS, Off Special Programs, Res Triangle Pk, NC 27709 USA. RP Boorman, GA (reprint author), NIEHS, Off Special Programs, POB 12233, Res Triangle Pk, NC 27709 USA. NR 56 TC 30 Z9 30 U1 0 U2 2 PU SOC TOXICOLOGIC PATHOLOGISTS PI MT ROYAL PA 19 MANTUA RD, MT ROYAL, NJ 08061 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAY-JUN PY 1999 VL 27 IS 3 BP 267 EP 278 DI 10.1177/019262339902700301 PG 12 WC Pathology; Toxicology SC Pathology; Toxicology GA 199KB UT WOS:000080479100001 PM 10356702 ER PT J AU Nyska, A Maronpot, RR Long, PH Roycroft, JH Hailey, JR Travlos, GS Ghanayem, BI AF Nyska, A Maronpot, RR Long, PH Roycroft, JH Hailey, JR Travlos, GS Ghanayem, BI TI Disseminated thrombosis and bone infarction in female rats following inhalation exposure to 2-butoxyethanol SO TOXICOLOGIC PATHOLOGY LA English DT Article DE rodent; ethylene glycol monobutyl ether; hemolysis; thrombosis; nasal cavity; bone ID SICKLE-CELL DISEASE; MONOBUTYL ETHER 2-BUTOXYETHANOL; BUTOXYACETIC ACID; ANEMIA; BLOOD; FAT; METABOLITE; DISORDERS; TOXICITY; PATIENT AB Groups of 10 male and 10 female F344/N rats were exposed to 0, 31, 62.5, 125, 2501 and 500 ppm of 2-butoxyethanol (BE) by inhalation, 6 hr/day, 5 days/wk, for 13 wk. Four moribund female rats from the 500 ppm group were sacrificed during the first 4 days of exposure, and 1 moribund female from the same group was sacrificed during week 5. Dark irregular mottling and/or loss of the distal rail were noted in sacrificed moribund rats. Similar gross lesions were noted in the terminally sacrificed females exposed to 500 ppm BE. Histologic changes noted in the day 4 sacrificed moribund rats included disseminated thrombosis involving the coccygeal, vertebrae, cardiac atrium, lungs, liver, pulp of the incisor teeth, and the submucosa of the anterior section of the nasal cavity. Alterations noted in coccygeal vertebrae from the 500 ppm sacrificed moribund rats included ischemic necrosis and/or degeneration of bone marrow cells, bone-lining cells, osteocytes (within cortical and trabecular bone), and chondrocytes (both articular and growth plate), changes that are consistent with an infarction process. The moribund female rat that was sacrificed during week 5 and those female rats treated with 500 ppm and sacrificed following 13 wk of treatment lacked thrombi, but they had coccygeal vertebral changes consistent with prior infarction and transient or complete bone growth arrest. No bone lesions or thrombi were noted in the male rats treated with the same doses of BE. In conclusion, exposure to 500 ppm BE vapors caused acute disseminated thrombosis and bone infarction in female rats. Possible pathogenic mechanisms are discussed. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Nyska, A (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 44 TC 16 Z9 17 U1 0 U2 1 PU SOC TOXICOLOGIC PATHOLOGISTS PI MT ROYAL PA 19 MANTUA RD, MT ROYAL, NJ 08061 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAY-JUN PY 1999 VL 27 IS 3 BP 287 EP 294 DI 10.1177/019262339902700304 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA 199KB UT WOS:000080479100004 PM 10356705 ER PT J AU Yoshida, A Newbold, RR Dixon, D AF Yoshida, A Newbold, RR Dixon, D TI Effects of neonatal diethylstilbestrol (DES) exposure on morphology and growth patterns of endometrial epithelial cells in CD-1 mice SO TOXICOLOGIC PATHOLOGY LA English DT Article DE neonatal mouse; uterus; ultrastructure; immunohistochemistry; bromodeoxyuridine; apoptosis; endocrine disrupters; environmental estrogens ID GENITAL-TRACT; MOUSE UTERUS; ESTROGENS; APOPTOSIS; HISTOLOGY; INDUCTION; RECEPTOR; ALTERS AB The effects of neonatal diethylstilbestrol (DES) exposure on the morphology and proliferating patterns of endometrial epithelial cells were investigated at various stages of development in mice. Female CD-I mice were given daily subcutaneous injections of 2 mu g of DES in corn oil or corn oil alone (control) at 1-5 days of age and were killed at 5, 6, 7, 8, 15, and 22 days of age. At 5 days of age, the uteri of DES-treated mice had expanded lumina and undulated luminal surfaces lined by slightly elongated epithelial cells. Ar 6-8 days of age, marked infolding of clusters of hypertrophic elongated luminal epithelial cells was present; uteri had disorganized endometrial stromal and myometrial layers. At 15 and 22 days of age, the tissues from DES-treated mice had decreased numbers of endometrial glands, minimal stromal fibrosis, and smaller uterine horns than did the controls. Ultrastructurally, the endometrial epithelial cells of DES-treated mice at 5 and 8 days of age had distorted nuclei with condensed matrix and abundant secretory granules associated with rough endoplasmic reticulum and Golgi apparatus. At 8 days of age, an accumulation of fingerlike cytoplasmic processes that extended into the separated intercellular spaces and along the basal aspects of the endometrial epithelial cells were also observed. At 5-8 days of age, the proliferative activity of endometrial epithelial cells in DES-treated mice, identified by bromodeoxyuridine labeling, was significantly lower (10.5-1.7%) than that of the controls (25.5-19.8%). In situ analysis of endometrial luminal epithelial cells for DNA fragmentation representing apoptosis revealed less than or equal to 0.1% and >10% in the DES-treated and control mice at 5-; 8 days of age, respectively. The data show that cell cycle kinetics, in addition to changes in morphology, are altered in the developing mouse uterus following neonatal exposure to DES. C1 NIEHS, Expt Pathol Lab, Res Triangle Pk, NC 27709 USA. RP Dixon, D (reprint author), NIEHS, Expt Pathol Lab, POB 12233,MD C2-09, Res Triangle Pk, NC 27709 USA. NR 32 TC 24 Z9 24 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI MT ROYAL PA 19 MANTUA RD, MT ROYAL, NJ 08061 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAY-JUN PY 1999 VL 27 IS 3 BP 325 EP 333 DI 10.1177/019262339902700308 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA 199KB UT WOS:000080479100008 PM 10356709 ER PT J AU Goering, PL Aposhian, HV Mass, MJ Cebrian, M Beck, BD Waalkes, MP AF Goering, PL Aposhian, HV Mass, MJ Cebrian, M Beck, BD Waalkes, MP TI The enigma of arsenic carcinogenesis: Role of metabolism SO TOXICOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the Society-of-Toxicology CY MAR 01-05, 1998 CL SEATTLE, WASHINGTON SP Soc Toxicol ID TUMOR-SUPPRESSOR GENE; ENZYMATIC METHYLATION; IN-VITRO; MONOMETHYLARSONIC ACID; DRINKING-WATER; URINARY CONCENTRATIONS; MARMOSET MONKEYS; DNA METHYLATION; RABBIT LIVER; RAT-LIVER AB Inorganic arsenic is considered a high-priority hazard, particularly because of its potential to be a human carcinogen. In exposed human populations, arsenic is associated with tumors of the lung, skin, bladder, and liver. While it is known to be a human carcinogen, carcinogenesis in laboratory animals by this metalloid has never been convincingly demonstrated. Therefore, no animal models exist for studying molecular mechanisms of arsenic carcinogenesis, The apparent human sensitivity, combined with our incomplete understanding about mechanisms of carcinogenic action, create important public health concerns and challenges in risk assessment, which could be met by understanding the role of metabolism in arsenic toxicity and carcinogenesis. This symposium summary covers three critical major areas involving arsenic metabolism: its biodiversity, the role of arsenic metabolism in molecular mechanisms of carcinogenesis, and the impact of arsenic metabolism on human risk assessment. In mammals, arsenic is metabolized to mono- and dimethylated species by methyltransferase enzymes in reactions that require S-adenosyl-methionine (SAM) as the methyl donating cofactor. A remarkable species diversity in arsenic methyltransferase activity may account for the wide variability in sensitivity of humans and animals to arsenic toxicity. Arsenic interferes with DNA methyltransferases, resulting in inactivation of tumor suppressor genes through DNA hypermethylation, Other studies suggest that arsenic-induced malignant transformation is linked to DNA hypomethylation subsequent to depletion of SAM, which results in aberrant gene activation, including oncogenes, Urinary profiles of arsenic metabolites may be a valuable tool for assessing human susceptibility to arsenic carcinogenesis. While controversial, the idea that unique arsenic metabolic properties may explain the apparent non-linear threshold response for arsenic carcinogenesis in humans. In order to address these outstanding issues, further efforts are required to identify an appropriate animal model to elucidate carcinogenic mechanisms of action, and to define dose-response relationships. C1 US FDA, Div Life Sci, Ctr Devices & Radiol Hlth, HFZ 112, Rockville, MD 20852 USA. Univ Arizona, Dept Mol & Cellular Biol, Tucson, AZ 85721 USA. Univ Arizona, Ctr Toxicol, Tucson, AZ 85721 USA. US EPA, Biochem & Pathobiol Branch, Div Environm Carcinogenesis, Natl Hlth & Environm Effects Lab, Res Triangle Pk, NC 27711 USA. CINVESTAV, Secc Toxicol Ambiental, Mexico City 14000, DF, Mexico. Gradient Corp, Cambridge, MA 02138 USA. NIEHS, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC USA. RP Goering, PL (reprint author), US FDA, Div Life Sci, Ctr Devices & Radiol Hlth, HFZ 112, 12709 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 58 TC 186 Z9 198 U1 2 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAY PY 1999 VL 49 IS 1 BP 5 EP 14 DI 10.1093/toxsci/49.1.5 PG 10 WC Toxicology SC Toxicology GA 251PX UT WOS:000083455000002 PM 10367337 ER PT J AU Bucher, JR Hailey, JR Roycroft, JR Haseman, JK Sills, RC Grumbein, SL Mellick, PW Chou, BJ AF Bucher, JR Hailey, JR Roycroft, JR Haseman, JK Sills, RC Grumbein, SL Mellick, PW Chou, BJ TI Inhalation toxicity and carcinogenicity studies of cobalt sulfate SO TOXICOLOGICAL SCIENCES LA English DT Article DE cobalt sulfate; alveolar/bronchiolar neoplasms; inhalation; respiratory toxicant; adrenal pheochromocytomas; carcinogenesis; B6C3F(1); mice; F344 rats ID HARD-METAL WORKERS; ANIMAL CARCINOGENICITY; B6C3F1 MICE; MORTALITY; EXPOSURE; INHIBITION; PROGRAM; COHORT; RATS AB Cobalt sulfate is a water-soluble cobalt salt with a variety of industrial and agricultural uses. Several cobalt compounds have induced sarcomas at injection sites in animals, and reports have suggested that exposure to cobalt-containing materials may cause lung cancer in humans. The present studies were done because no adequate rodent carcinogenicity studies had been performed with a soluble cobalt salt using a route relevant to occupational exposures. Groups of 50 male and 50 female F344/N rats and B6C3F(1) mice were exposed to aerosols containing 0, 0.3, 1.0, or 3.0 mg/m(3) cobalt sulfate hexahydrate, 6 h/day, 5 days/week, for 104 weeks. Survival and body weights of exposed rats and mice were generally unaffected by the exposures. In rats, proteinosis, alveolar epithelial metaplasia, granulomatous alveolar inflammation, and interstitial fibrosis were observed in the lung in all exposed groups. Nonneoplastic lesions of the nose and larynx were also attributed to exposure to all concentrations of cobalt sulfate. In 3.0 mg/m(3) male rats and in female rats exposed to 1.0 or 3.0 mg/m3, the incidences of alveolar/bronchiolar neoplasms were increased over those in the control groups. Lung tumors occurred with significant positive trends in both sexes. The incidences of adrenal pheochromocytoma in 1.0 mg/m3 male rats and in 3.0 mg/m3 female rats were increased. Nonneoplastic lesions of the respiratory tract were less severe in mice than in rats. In mice, alveolar/bronchiolar neoplasms in 3.0 mg/m3 males and females were greater than those in the controls, and lung tumors occurred with significantly positive trends. Male mice had liver lesions consistent with a Helicobacter hepaticus infection. Incidences of liver hemangiosarcomas were increased in exposed groups of male mice; however, because of the infection, no conclusion could be reached concerning an association between liver hemangiosarcomas and cobalt sulfate. In summary, exposure to cobalt sulfate by inhalation resulted in increased incidence of alveolar/bronchiolar neoplasms and a spectrum of inflammatory, fibrotic, and proliferative lesions in the respiratory tracts of male and female rats and mice. Adrenal pheochromocytomas were increased in female rats, and possibly in male rats. C1 NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. Pacific NW Lab, Richland, WA 99352 USA. RP Bucher, JR (reprint author), NIEHS, Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. NR 43 TC 52 Z9 53 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAY PY 1999 VL 49 IS 1 BP 56 EP 67 DI 10.1093/toxsci/49.1.56 PG 12 WC Toxicology SC Toxicology GA 251PX UT WOS:000083455000007 PM 10367342 ER PT J AU Lewis, JG Graham, DG Valentine, WM Morris, RW Morgan, DL Sills, RC AF Lewis, JG Graham, DG Valentine, WM Morris, RW Morgan, DL Sills, RC TI Exposure of C57BL/6 mice to carbon disulfide induces early lesions of atherosclerosis and enhances arterial fatty deposits induced by a high fat diet SO TOXICOLOGICAL SCIENCES LA English DT Article DE carbon disulfide; atherosclerosis; arterial fatty deposits; foam cells; high fat diet; spectrin; and inhalation ID LOW-DENSITY-LIPOPROTEIN; ISCHEMIC-HEART-DISEASE; HUMAN MONOCYTE-MACROPHAGES; CROSS-LINKING; MORTALITY; SUSCEPTIBILITY; NEUROTOXICITY; MORPHOLOGY; RESISTANCE; STRAINS AB Even though atherosclerotic cardiovascular disease (ACVD) is the number one cause of death in the United States, the effects of environmental toxicants on this process are less well studied than the effects of chemicals on the second leading cause of death, cancer. There is considerable epidemiological evidence that workers exposed to carbon disulfide (CS2) have increased rates of ACVD, and there is conflicting evidence of the atherogenic potential of CS2 from animal studies. Chemical modification, such as oxidation of low-density lipoproteins (LDL), is tightly associated with increased LDL uptake by macrophages and the development of arterial fatty streaks. CS2 has been previously demonstrated to modify several proteins in vitro including LDL, and others in vivo through derivatization and covalent cross-linking, To investigate both the capacity of CS2 to induce arterial fatty deposits by itself, and its ability to enhance the rate of fatty deposit formation induced by a western style, high fat diet, groups of 20 female C57BL/6 mice were exposed to 0, 50, 500, or 800 ppm CS2 by inhalation, Half the animals in each group were placed on an atherogenic high fat diet and half on a control diet (NIH-07), Animals were sacrificed after 1, 4, 8, 12, 16, or 20 weeks of exposure, and the rates of fatty deposit formation under the aortic valve leaflets were evaluated. Exposure of mice on the control diet to 500 and 800 ppm CS2 induced a small but significant increase in the rate of fatty deposit formation over non-exposed controls. A more striking result was observed in the animals on the high fat diet, There was marked enhancement of the rate of fatty deposit formation in mice exposed to 500 and 800 ppm over the animals on the high fat diet alone. In addition, there was a small but significant enhancement in mice exposed to 50 ppm over the rate of fatty deposit formation induced by the high fat diet alone, Analysis of erythrocyte spectrin for protein cross-linking revealed a dose-dependent formation of alpha- and beta-heterodimers in animals on both diets, These data demonstrate that CS2 is atherogenic at high concentrations, but more importantly, suggest that, in conjunction with other risk factors, CS2 at relatively low concentrations can enhance atherogenesis. C1 Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37232 USA. Analyt Sci Inc, Durham, NC 27713 USA. NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Lewis, JG (reprint author), Duke Univ, Med Ctr, Dept Pathol, Box 3712, Durham, NC 27710 USA. NR 45 TC 12 Z9 13 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 MAY PY 1999 VL 49 IS 1 BP 124 EP 132 DI 10.1093/toxsci/49.1.124 PG 9 WC Toxicology SC Toxicology GA 251PX UT WOS:000083455000015 PM 10367350 ER PT J AU van Birgelen, APJM Hebert, CD Wenk, ML Grimes, LK Chapin, RE Travlos, G Mahler, J Bucher, JR AF van Birgelen, APJM Hebert, CD Wenk, ML Grimes, LK Chapin, RE Travlos, G Mahler, J Bucher, JR TI Toxicity of 3,3 ',4,4 '-tetrachloroazoxybenzene in rats and mice SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the Society-of-Toxicology CY MAR 01-05, 1998 CL SEATTLE, WASHINGTON SP Soc Toxicol ID TCDD CONGENER 3,3',4,4'-TETRACHLOROAZOXYBENZENE; ARYL-HYDROCARBON HYDROXYLASE; THYROID-HORMONE METABOLISM; DIBENZO-P-DIOXINS; ZERO DOSE CONTROL; POLYCHLORINATED-BIPHENYLS; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN TCDD; LACTATIONAL EXPOSURE; HAIRLESS MICE; AH RECEPTOR AB The toxicity of 3,3'4,4'-tetrachloroazoxybenzene (TCAOB),vas evaluated in 13-meek gavage studies in male and female F44/N rats and B6C3F(1) mice. In addition to histopathology, evaluations included clinical chemistry, hematology, thyroid hormone analyses, and effects on sperm morphology and estrous cycle length. Groups of 10 rats and 10 mice of each sex were exposed to TCAOB at dose levels of 0, 0.1, 1, 3, 10, or 30 mg/kg 5 days a week for 13 weeks. In the rat studies, the major effects included death in the 30 mg TCAOB/kg dose group; at lower exposure levels, a decrease in body weight gain, a decrease in thymus weight, an increase in liver weight, an increase in hematopoietic cell proliferation in the spleen and liver, a responsive anemia, a decrease in platelet counts, a chronic active inflammation of the vasculature in the lung, an increase in cardiomyopathy, hyperplasia of the forestomach, and a marked decrease in circulating thyroxine concentrations were observed. In male rats a decrease in sperm motility in the epididymides was observed. In addition, in female rats an increase in lung, spleen, kidney, and heart weights and nephropathy was observed. Furthermore, the estrous cycle length was increased. In the mouse studies, the major effects for males; and females included a decrease in thymus weights, an increase in liver and kidney weights, centrilobular hypertrophy in the liver, hematopoietic cell proliferation, hyperplasia of the forestomach, and dilatation of hair follicles. The spectrum of effects in both rats and mice after exposure to TCAOB indicates that dioxin-like effects occur in addition to effects that have not been observed with dixon-like compounds. No no-observed-adverse-effect level was reached in male or female rats or mice. (C) 1999 Academic Press. C1 NIEHS, Res Triangle Pk, NC 27709 USA. MA Biosci Inc, Rockville, MD 20850 USA. Environm Hlth Res & Testing Inc, Lexington, KY USA. RP van Birgelen, APJM (reprint author), NIEHS, POB 12233,MD B3-07, Res Triangle Pk, NC 27709 USA. OI Chapin, Robert/0000-0002-5997-1261 NR 91 TC 6 Z9 6 U1 0 U2 2 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 MAY 1 PY 1999 VL 156 IS 3 BP 206 EP 221 DI 10.1006/taap.1999.8647 PG 16 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 196NT UT WOS:000080315000006 PM 10222313 ER PT J AU Chen, E Gadina, M Chen, M O'Shea, JJ AF Chen, E Gadina, M Chen, M O'Shea, JJ TI Advances in cytokine signaling: The role of Jaks and STATs SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 5th Basic Sciences Symposium of the Transplantation-Society CY SEP 06-11, 1997 CL CHAUTAUQUA, NEW YORK SP Transplantat Soc, Ernest Witebsky Ctr Immunol, SUNY Buffalo, Sch Med & Biomed Sci ID SEVERE COMBINED IMMUNODEFICIENCY; MICE LACKING JAK3; TARGETED DISRUPTION; DEVELOPMENTAL DEFECTS; LYMPHOID DEVELOPMENT; DEFICIENT MICE; T-LYMPHOCYTES; ABL ONCOGENE; TH2 CELLS; RECEPTOR C1 NIAMSD, Lymphocyte Cell Biol Sect, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. RP O'Shea, JJ (reprint author), NIAMSD, Lymphocyte Cell Biol Sect, Arthrit & Rheumatism Branch, NIH, Bldg 10,Room 9N252,10 Ctr Dr MSC-1820, Bethesda, MD 20892 USA. NR 71 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD MAY PY 1999 VL 31 IS 3 BP 1482 EP 1487 DI 10.1016/S0041-1345(99)00013-5 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 195CR UT WOS:000080232000011 PM 10330976 ER PT J AU Remmers, EF Griffiths, MM Longman, RE Gulko, PS Kawahito, Y Chen, S Chang, L Shepard, J Ge, L Dracheva, S Wang, JP Joe, B Cannon, GW Wilder, RL AF Remmers, EF Griffiths, MM Longman, RE Gulko, PS Kawahito, Y Chen, S Chang, L Shepard, J Ge, L Dracheva, S Wang, JP Joe, B Cannon, GW Wilder, RL TI An integrated rat genetic map: Analysis of linkage conservation with the mouse and human maps SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 12th International Workshop on Alloantigenic Systems in the Rat CY JUL 08-10, 1998 CL HALIFAX, CANADA SP Roche Pharmaceut, Novartis Pharma Canada Inc, SangStat Med Corp, Wyeth Ayerst, Fujisawa Canada Inc ID INDUCED ARTHRITIS; LOCALIZATION C1 Natl Inst Arthrit & Musculoskeletal & Skin Dis, Inflammatory Joint Dis Sect, NIH, Bethesda, MD 20892 USA. Vet Affairs Med Ctr, Res Serv, Salt Lake City, UT 84148 USA. Univ Utah, Dept Med Rheumatol, Salt Lake City, UT 84148 USA. RP Remmers, EF (reprint author), Natl Inst Arthrit & Musculoskeletal & Skin Dis, Inflammatory Joint Dis Sect, NIH, Bldg 10 Room 9N228,10 Ctr Dr MSC1820, Bethesda, MD 20892 USA. NR 5 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD MAY PY 1999 VL 31 IS 3 BP 1549 EP 1554 DI 10.1016/S0041-1345(99)00032-9 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 195CR UT WOS:000080232000032 PM 10330996 ER PT J AU Wilder, RL Griffiths, MM Remmers, EF Cannon, GW Caspi, RR Kawahito, Y Gulko, PS Longman, RE Dracheva, SV Du, Y Sun, SH Wang, J Shepard, JS Joe, B Le, G Chen, S Chang, L Hoffman, J Silver, PB Reese, VR AF Wilder, RL Griffiths, MM Remmers, EF Cannon, GW Caspi, RR Kawahito, Y Gulko, PS Longman, RE Dracheva, SV Du, Y Sun, SH Wang, J Shepard, JS Joe, B Le, G Chen, S Chang, L Hoffman, J Silver, PB Reese, VR TI Localization in rats of genetic loci regulating susceptibility to experimental erosive arthritis and related autoimmune diseases SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 12th International Workshop on Alloantigenic Systems in the Rat CY JUL 08-10, 1998 CL HALIFAX, CANADA SP Roche Pharmaceut, Novartis Pharma Canada Inc, SangStat Med Corp, Wyeth Ayerst, Fujisawa Canada Inc ID BB RAT; ADJUVANT C1 Natl Inst Arthrit & Musculoskeletal & Skin Dis, Inflammatory Joint Dis Sect, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Wilder, RL (reprint author), Natl Inst Arthrit & Musculoskeletal & Skin Dis, Inflammatory Joint Dis Sect, Arthrit & Rheumatism Branch, NIH, Bldg 10,Room 9N228,10 Ctr Dr, Bethesda, MD 20892 USA. NR 15 TC 26 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD MAY PY 1999 VL 31 IS 3 BP 1585 EP 1588 DI 10.1016/S0041-1345(99)00047-0 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 195CR UT WOS:000080232000047 PM 10331011 ER PT J AU Ponting, CP Bork, P Schultz, J Aravind, L AF Ponting, CP Bork, P Schultz, J Aravind, L TI No Sec7-homology domain in guanine-nucleotide-exchange factors that act on Ras and Rho SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Letter ID SEC7 DOMAIN; ARF GTPASE; ARNO C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. European Mol Biol Lab, D-69012 Heidelberg, Germany. RP Ponting, CP (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A, Bethesda, MD 20894 USA. RI Schultz, Joerg/B-9346-2008; Bork, Peer/F-1813-2013 OI Bork, Peer/0000-0002-2627-833X NR 15 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD MAY PY 1999 VL 24 IS 5 BP 177 EP 178 DI 10.1016/S0968-0004(99)01379-1 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 196CK UT WOS:000080291300005 PM 10322430 ER PT J AU Murga, C Fukuhara, S Gutkind, JS AF Murga, C Fukuhara, S Gutkind, JS TI Novel molecular mediators in the pathway connecting G-protein-coupled receptors to MAP kinase cascades SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID HETEROTRIMERIC G-PROTEINS; BETA-GAMMA-SUBUNITS; SIGNAL-TRANSDUCTION; DIRECT STIMULATION; BINDING PROTEINS; TYROSINE-KINASE; P115 RHOGEF; ACTIVATION; FAMILY; APOPTOSIS AB The family of receptors coupled to heterotrimeric GTP-binding proteins (G proteins) constitutes the largest group of integral membrane proteins involved in signal transduction. These receptors participate in many important biological functions, ranging from photoreception to neurotransmission and exocytosis, as well as in processes such as embryogenesis, angiogenesis, tissue regeneration and normal and aberrant cell growth. Initial studies addressing the functioning of these receptors had focused primarily on second messenger-generating systems. Here, the authors survey the current knowledge on how this family of receptors transduces signals to the nucleus through an intricate network of nucleotide exchange factors, small GTPases, and cytoplasmic kinases which, in turn, control gene expression by phosphorylating nuclear regulatory molecules. C1 Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Murga, C (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009; Murga, Cristina/E-1965-2014 OI Murga, Cristina/0000-0002-8964-4077 NR 48 TC 39 Z9 39 U1 0 U2 1 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 MAY PY 1999 VL 10 IS 4 BP 122 EP 127 DI 10.1016/S1043-2760(98)00131-3 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 214LU UT WOS:000081330100002 ER PT J AU Li, Q Sachs, L Shi, YB Wolffe, AP AF Li, Q Sachs, L Shi, YB Wolffe, AP TI Modification of chromatin structure by the thyroid hormone receptor SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID GLUCOCORTICOID RESPONSE ELEMENT; HISTONE DEACETYLASE; TRANSCRIPTIONAL REPRESSION; PROMYELOCYTIC LEUKEMIA; CO-REPRESSOR; COMPLEX; ACTIVATION; NUCLEOSOME; GENE; ACETYLATION AB Pioneering experiments and recent observations have established the thyroid hormone receptor as a master manipulator of the chromosomal environment in targeting the activation and repression of transcription. Here we review how the thyroid hormone receptor is assembled into chromatin, where in the absence of thyroid hormone the receptor recruits histone deacetylase to silence transcription. On addition of hormone, the receptor undergoes a conformational change that leads to the release of deacetylase, while facilitating the recruitment of transcriptional coactivators that act as histone acetyltransferases. We discuss the biological importance of these observations for gene control by the thyroid hormone receptor and Ibr oncogenic transformation by the mutated thyroid hormone receptor v-ErbA. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Li, Q (reprint author), NICHHD, Mol Embryol Lab, NIH, Bldg 18T,Rm 106, Bethesda, MD 20892 USA. OI Li, Qiao/0000-0002-5941-1985 NR 41 TC 26 Z9 26 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 MAY PY 1999 VL 10 IS 4 BP 157 EP 164 DI 10.1016/S1043-2760(98)00141-6 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 214LU UT WOS:000081330100008 ER PT J AU Wolf, YI Aravind, L Koonin, EV AF Wolf, YI Aravind, L Koonin, EV TI Rickettsiae and Chlamydiae - evidence of horizontal gene transfer and gene exchange SO TRENDS IN GENETICS LA English DT Article ID PROTEIN SEQUENCES; GENOME SEQUENCE; ARCHAEAL; PROWAZEKII; ORIGIN C1 NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia. RP Wolf, YI (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. NR 15 TC 106 Z9 109 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD MAY PY 1999 VL 15 IS 5 BP 173 EP 175 DI 10.1016/S0168-9525(99)01704-7 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 215KC UT WOS:000081380000004 PM 10322483 ER PT J AU Thomas, BI Wassarman, DA AF Thomas, BI Wassarman, DA TI A fly's eye view of biology SO TRENDS IN GENETICS LA English DT Review ID DEVELOPING DROSOPHILA EYE; CELL-DEATH; ECTOPIC EXPRESSION; SIGNALING PATHWAY; TISSUE POLARITY; VISUAL-SYSTEM; PROTEIN; GENE; SCREEN; ACTIVATION AB Determining how genes function in developmentally complex multicellular organisms can be a formidable task. Obstacles arise from the fact that inactivation of most genes results in subtle or undetectable phenotypic alterations, and when phenotypes are observed they are often difficult to interpret because most genes play multiple roles in development. New techniques that have been applied to studying genes in the developing Drosophila eye promise to circumvent these obstacles. The advent of these techniques combined with the existing wealth of information about cellular pattern formation in the Drosophila eye make the eye a powerful model system for deciphering the function of genes in biological processes. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Thomas, BI (reprint author), NCI, Biochem Lab, NIH, Bldg 37,Room 4C17, Bethesda, MD 20892 USA. NR 48 TC 39 Z9 40 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD MAY PY 1999 VL 15 IS 5 BP 184 EP 190 DI 10.1016/S0168-9525(99)01720-5 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 215KC UT WOS:000081380000008 PM 10322485 ER PT J AU McBain, CJ Freund, TE Mody, I AF McBain, CJ Freund, TE Mody, I TI Glutamatergic synapses onto hippocampal interneurons: precision timing without lasting plasticity SO TRENDS IN NEUROSCIENCES LA English DT Review ID LONG-TERM POTENTIATION; RAT HIPPOCAMPUS; SYNAPTIC PLASTICITY; DENDRITIC SPINES; AREA CA1; NEURONS; CALCIUM; MODEL; DEPRESSION; ACTIVATION AB In the hippocampal formation GABAergic inhibitory interneurons have a major role in the synchronization of neuronal activity and are involved in the generation of large-scale network oscillations. hus, interneurons function as a 'clock' that dictates when principal cells fire during suprathreshold excitatory drive. Interneurons receive strong excitatory innervation from glutamatergic neurons and it has been much debated whether these synapses show mechanisms of long-term plasticity similar to those found at principal-cell synapses. Recent findings support the lack of conventional forms of LTP and LTD in most interneurons, partly owing to the distinct anatomical and neurochemical features of interneuronal excitatory synapses. The uncommon properties of excitatory synapses on interneurons might be required for their functioning as accurate and reliable neuronal oscillators. C1 NICHD, Lab Cellular & Mol Neurophysiol, Bethesda, MD 20892 USA. Hungarian Acad Sci, Inst Expt Med, H-1450 Budapest, Hungary. Univ Calif Los Angeles, Sch Med, Dept Neurol RNRC 3 131, Los Angeles, CA 90095 USA. RP McBain, CJ (reprint author), NICHD, Lab Cellular & Mol Neurophysiol, Bethesda, MD 20892 USA. NR 61 TC 84 Z9 85 U1 1 U2 3 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD MAY PY 1999 VL 22 IS 5 BP 228 EP 235 DI 10.1016/S0166-2236(98)01347-2 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 215JE UT WOS:000081377900009 PM 10322496 ER PT J AU Liberski, PP Buczynski, J Yanagihara, R Mora, C Gibbs, CJ Gajdusek, DC Cartier, L Verdugo, A Araya, F Castillo, L AF Liberski, PP Buczynski, J Yanagihara, R Mora, C Gibbs, CJ Gajdusek, DC Cartier, L Verdugo, A Araya, F Castillo, L TI Ultrastructural pathology of a Chilean case of tropical spastic paraparesis human T-cell lymphotropic type I-associated myelopathy (TSP/HAM) SO ULTRASTRUCTURAL PATHOLOGY LA English DT Article DE human T-cell lymphotropic virus type I; multilamellar bodies; retroviruses; tropical spastic paraparesis ID VIRUS TYPE-I; SPINAL-CORD LESIONS; HTLV-I AB Human T-cell lymphotropic virus type I (HTLV-I), is the cause of endemic tropical spastic paraparesis (TSP) or HTLV-I-associated myelopathy (HAM). Because TSP/HAM is not a fatal disease, the neuropathology of this disease, albeit relatively well understood, is based on the examination of just a few incidental cases. Previously, we demonstrated peculiar lamellated structures, called "multilamellar bodies" (MLB). In this report, we present the ultrastructural neuropathology of a TSP/HAM case from Chile, with further detailed descriptions of MLB. It is tempting to suggest that MLB may represent specific ultrastructural markers of TSP/HAM. The pathology of the anterior and posterior horns was similar and was comprised of axonal degeneration, accompanied by extensive astrocytic gliosis. Lymphocytic infiltration, particularly observed as "cuffs" around blood vessels, was scattered among Other cellular elements. Ultrastructurally, myelin sheaths were relatively well preserved, and some demyelinated but not remyelinated fibers were observed. Moreover, axons with abnormal accumulations of neurofilaments, suggestive of axonal degeneration, were detected. Several axons contained Hirano bodies. In many samples, glial processes replaced most of the remaining neuropil. In a few specimens of the anterior and posterior horns of the spinal cord, MLB were observed. These structures consisted of stacks of 30 to 40 electron-dense lamellae, which were interrupted by narrow electron-lucent spaces. All of the lamellae were immersed within an amorphous substance of intermediate density. Neurons of the dorsal root ganglia were basically normal except for increased lipofuscin accumulation. As in the spinal cord, myelinated axons were well preserved, but a few were demyelinated and surrounded by concentric arrays of Schwann cell membranes. Also, axons of the dorsal roots accumulated increased number of neurofilaments. Mast cells and Schwann cells were increased in number, the latter containing abundant pi granules and myelin fragments. C1 Med Acad Lodz, Dept Mol Biol, Lab Electron Microscopy & Neuropathol, PL-93509 Lodz, Poland. Med Acad Lodz, Dept Oncol, Lab Elect Microscopy & Neuropathol, Labs Tumor Biol, PL-93509 Lodz, Poland. NINDS, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD 20892 USA. Univ Chile, Dept Neurol Sci, Santiago, Chile. RP Liberski, PP (reprint author), Med Acad Lodz, Dept Mol Biol, Lab Electron Microscopy & Neuropathol, Paderewskiego 4, PL-93509 Lodz, Poland. NR 25 TC 7 Z9 7 U1 1 U2 1 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 USA SN 0191-3123 J9 ULTRASTRUCT PATHOL JI Ultrastruct. Pathol. PD MAY-JUN PY 1999 VL 23 IS 3 BP 157 EP 162 PG 6 WC Microscopy; Pathology SC Microscopy; Pathology GA 210JA UT WOS:000081100300003 PM 10445282 ER PT J AU Connaughton, VP Behar, TN Liu, WLS Massey, SC AF Connaughton, VP Behar, TN Liu, WLS Massey, SC TI Immunocytochemical localization of excitatory and inhibitory neurotransmitters in the zebrafish retina SO VISUAL NEUROSCIENCE LA English DT Article DE glutamate; GABA; GAD(65); GAD(67); glycine; zebrafish ID GLUTAMIC-ACID DECARBOXYLASE; GOLDFISH RETINA; BIPOLAR CELLS; HORIZONTAL CELLS; AMACRINE CELLS; INTERPLEXIFORM CELLS; GLYCINERGIC PATHWAYS; SYNAPTIC TERMINALS; CAT RETINA; GABA AB The patterns of glutamate, gamma-aminobutyric acid (GABA), and glycine distribution in the zebrafish retina were determined using immunocytochemical localization of antisera at the light-microscope level. The observed GABA immunoreactivity (GABA-IR) patterns were further characterized using antibodies to both isoforms of glutamic acid decarboxylase (GAD(65) and GAD(67)), the synthetic enzyme for GABA. Glutamate-IR was observed in all retinal layers with photoreceptors, bipolar calls, and ganglion cells prominently labeled. Bipolar cells displayed the most intense glutamate-IR and bipolar cell axon terminals were clearly identified as puncta arranged in layers throughout the inner plexiform layer (IPL). These findings suggest the presence of multiple subtypes of presumed OFF- and ON-bipolar cells, including some ON-bipolar cells characterized by a single, large (9 mu m X 6 mu m) axon terminal. GABA-, GAD-, and glycine-IR were most intense in the inner retina. In general, the observed labeling patterns for GABA, GAD(65), and GAD(67) were similar. GABA- and GAD-IR were observed in a population of amacrine cells, a few cells in the ganglion cell layer, throughout the IPL, and in horizontal cells. In the IPL, both GABA- and GAD-IR structures were organized into two broad bands. Glycine-IR was observed in amacrine cells, interplexiform cells, and in both plexiform layers. Glycine-positive terminals were identified throughout the IPL, with a prominent band in sublamina 3 corresponding to an immunonegative region observed in sections stained for GAD and GABA. Our results show the distribution of neurons in the zebrafish retina that use glutamate, GABA, or glycine as their neurotransmitter. The observed distribution of neurotransmitters in the inner retina is consistent with previous studies of other vertebrates and suggests that the advantages of zebrafish for developmental studies may be exploited for retinal studies. C1 NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. Univ Texas, Sch Med, Dept Ophthalmol & Visual Sci, Houston, TX USA. RP Connaughton, VP (reprint author), NINDS, Neurophysiol Lab, NIH, Bldg 36,Room 2C02,36 Convent Dr MSC 4066, Bethesda, MD 20892 USA. FU NEI NIH HHS [EY 06515, EY 06640, EY 10608] NR 49 TC 43 Z9 43 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0952-5238 J9 VISUAL NEUROSCI JI Visual Neurosci. PD MAY-JUN PY 1999 VL 16 IS 3 BP 483 EP 490 PG 8 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 195DN UT WOS:000080234000009 PM 10349969 ER PT J AU Kastner, S Nothdurft, HC Pigarev, IN AF Kastner, S Nothdurft, HC Pigarev, IN TI Neuronal responses to orientation and motion contrast in cat striate cortex SO VISUAL NEUROSCIENCE LA English DT Article DE cat striate cortex; single-cell recordings; classical receptive field; contextual response modulation; pop-out ID PRIMARY VISUAL-CORTEX; MOVING TEXTURED BACKGROUNDS; CLASSICAL RECEPTIVE-FIELD; PREATTENTIVE VISION; POP-OUT; SEGREGATION; CELLS; SENSITIVITY; INHIBITION; PATTERNS AB Responses of striate neurons to line textures were investigated in anesthetized and paralyzed adult cars. Light bars centered over the excitatory receptive field (RF) were presented with different texture surrounds composed of many similar bars. In two test series, responses of 169 neurons to textures with orientation contrast (surrounding bars orthogonal to the center bar) or motion contrast (surrounding bars moving opposite to the center bar) were compared to the responses to the corresponding uniform texture conditions (all lines parallel, coherent motion) and to the center bar alone. In the majority of neurons center bar responses were suppressed by the texture surrounds. Two main effects were found. Some neurons were generally suppressed by either texture surround. Other neurons were less suppressed by texture displaying orientation or motion (i.e. feature) contrast than by the respective uniform texture, so that their responses to orientation or motion contrast appeared to be relatively enhanced (preference for feature contrast). General suppression was obtained in 33% of neurons tested for orientation and in 19% of neurons tested for motion. Preference for orientation or motion contrast was obtained in 22% and 34% of the neurons, respectively, and was also seen in the mean response of the population. One hundred nineteen neurons were studied in both orientation and motion tests. General suppression was correlated across the orientation and motion dimension, but not preference for feature contrast. We also distinguished modulatory effects from end-zones and flanks using butterfly-configured texture patterns. Both regions contributed to the generally suppressive effects. Preference for orientation or motion contrast was not generated from either end-zones or flanks exclusively. Neurons with preference for feature contrast may form the physiological basis of the perceptual saliency of pop-out elements in line textures, If so, pop-out of motion and pop-out of orientation would be encoded in different pools of neurons at the level of striate cortex. C1 Max Planck Inst Biophys Chem, AG Neurobiol, D-37070 Gottingen, Germany. RP Kastner, S (reprint author), NIMH, Lab Brain & Cognit, NIH, Bldg 49,Room 1B80, Bethesda, MD 20892 USA. NR 50 TC 49 Z9 50 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0952-5238 J9 VISUAL NEUROSCI JI Visual Neurosci. PD MAY-JUN PY 1999 VL 16 IS 3 BP 587 EP 600 DI 10.1017/S095252389916317X PG 14 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 195DN UT WOS:000080234000017 PM 10349977 ER PT J AU Yaffe, K Yaffe, SJ AF Yaffe, K Yaffe, SJ TI Long-term cognitive effects of drugs used during labor - Comment SO WESTERN JOURNAL OF MEDICINE LA English DT Editorial Material C1 Univ Calif San Francisco, Dept Psychiat & Neurol, San Francisco, CA 94121 USA. NICHHD, Ctr Res Mothers & Children, NIH, Bethesda, MD 20892 USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat & Neurol, 4150 Clement St, San Francisco, CA 94121 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD MAY PY 1999 VL 170 IS 5 BP 262 EP 262 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 203DV UT WOS:000080693100009 PM 18751141 ER PT J AU Wysocki, AB Kusakabe, AO Chang, S Tuan, TL AF Wysocki, AB Kusakabe, AO Chang, S Tuan, TL TI Temporal expression of urokinase plasminogen activator, plasminogen activator inhibitor and gelatinase-B in chronic wound fluid switches from a chronic to acute wound profile with progression to healing SO WOUND REPAIR AND REGENERATION LA English DT Article ID CHRONIC LEG ULCERS; TUMOR INVASION; CELL-GROWTH; TISSUE; METALLOPROTEINASES; COLLAGENASE; RECEPTOR; SYSTEM; FIBRONECTIN; DEGRADATION AB The plasminogen activator/plasmin system is known to initiate a proteolytic cascade resulting in the activation of matrix metalloproteinases in vitro leading to the degradation of extracellular matrix. To investigate whether or not this cascade is present during delayed wound healing and contributes to the pathophysiological basis of impaired healing we examined the temporal expression of urokinase plasminogen activator, plasminogen activator inhibitor-1 and gelatinase-B in fluid collected from chronic venous leg ulcers compared to acute surgical mastectomy wounds. Using a chromogenic substrate assay, levels of active urokinase plasminogen activator in chronic wounds were found to be about five fold higher compared to sera and two fold higher compared to mastectomy wounds, Levels of active plasminogen activator inhibitor-1 in chronic wounds were four times higher than those found in sera and two times higher than those found in mastectomy wound fluid. Using a fibrin overlay system and reverse zymography, we found that when the wound was not healing, the expression of urokinase plasminogen activator in chronic wound fluid was initially detected in the active forms (50 and 33 kDa), but that as the wound healed and decreased in size, was detected as an inhibitor-bound urokinase plasminogen activator-plasminogen activator inhibitor-1 complex (approximate to 80-116 kDa), When the expression of active urokinase plasminogen activator was highest, no plasminogen activator inhibitor-1 was detectable. In contrast, urokinase plasminogen activator was always detected in the inhibitor bound form as a urokinase plasminogen activator-plasminogen activator inhibitor-1 complex in blood- and plasma-derived serum and mastectomy wound fluid. Plasminogen activator inhibitor-1 was detected in blood-derived serum and mastectomy wound fluid but not in plasma derived serum. Expression of matrix metalloproteinase-9 in chronic wound fluids, analyzed by gelatin zymography, showed that when urokinase plasminogen activator was detected in the active forms, matrix metalloproteinase-9 was overexpressed by approximately twice that found in mastectomy wounds and approximately 30 times that detected in blood-derived sera. When urokinase plasminogen activator appeared almost entirely as an enzyme-inhibitor complex, the level of expression of matrix metalloproteinase-9 was similar to that seen in mastectomy wound fluid. We conclude that the switch in urokinase plasminogen activator expression from an active to inhibitor bound form correlates with the decrease seen in matrix metalloproteinase-9 expression suggesting the presence of a proteolytic cascade initiated by the plasminogen activator/plasmin system during wound healing leading to the activation of matrix metalloproteinase-9. In addition, expression of urokinase plasminogen activator and matrix metalloproteinase-9 appear to be useful biomarkers to determine clinical wound healing status. C1 Natl Inst Nursing Res, Wound Healing Lab, Bethesda, MD 20892 USA. NYU Med Ctr, Dept Nursing, New York, NY 10016 USA. NYU Med Ctr, Ronald O Perelman Dept Dermatol, New York, NY 10016 USA. Univ So Calif, Sch Med, Los Angeles, CA USA. Childrens Hosp Los Angeles, Dept Surg, Los Angeles, CA 90027 USA. RP Wysocki, AB (reprint author), Natl Inst Nursing Res, Wound Healing Lab, 9 Ctr Dr MSC 0967,Bldg 9,Room 1 W125, Bethesda, MD 20892 USA. FU NIGMS NIH HHS [GM55081]; NINR NIH HHS [NR03212] NR 49 TC 80 Z9 83 U1 1 U2 4 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD MAY-JUN PY 1999 VL 7 IS 3 BP 154 EP 165 DI 10.1046/j.1524-475X.1999.00154.x PG 12 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 213AZ UT WOS:000081251000005 PM 10417751 ER PT J AU Boehm, T Pirie-Shepherd, S Trinh, LB Shiloach, J Folkman, J AF Boehm, T Pirie-Shepherd, S Trinh, LB Shiloach, J Folkman, J TI Disruption of the KEX1 gene in Pichia pastoris allows expression of full-length murine and human endostatin SO YEAST LA English DT Article DE Pichia pastoris; KEX1 disruption; endostatin ID HIGH-LEVEL SECRETION; SACCHAROMYCES-CEREVISIAE; YEAST; CARBOXYPEPTIDASE; ANGIOGENESIS; ANGIOSTATIN; INHIBITOR; GROWTH AB Endostatin is a potent angiogenesis inhibitor. In order to isolate sufficient quantities of soluble protein for in vivo studies in mice, we expressed murine endostatin in Pichia pastoris. Analysis of the expressed protein by mass spectrometry indicated that the protein was truncated. N-terminal sequence analysis determined that the N-terminus was intact, suggesting that the C-terminal lysine was missing. In Saccharomyces cerevisiae, Kex1p can cleave lysine and arginine residues from the C-terminus of peptides and proteins. We hypothesized that the KEX1 homologue in P. pastoris is responsible for the loss of the C-terminal lysine of endostatin. To test this hypothesis, we cloned and disrupted the P. pastoris KEX1 gene. Although the overall amino acid identity between the P. pastoris and the S. cerevisae Kex1p is only 36%, the amino acid residues involved in the catalytic activity or close to the active residues are highly conserved. Disruption of the KEX1 reading frame allowed expression of murine and human endostatin with the C-terminal lysine. The KEX1 disruption strain map be a useful tool for the expression of other proteins with a C-terminal basic amino acid. Addition of a lysine to the C-terminus of recombinant proteins may protect the C-terminus from degradation by other carboxypeptidases. 3.5 kb of the P. pastoris KEX1 gene locus have been deposited in the GeneBank database and are available under Accession No. AF095574. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cellular Biol, Boston, MA 02115 USA. NIDDKD, Biotechnol Unit, Bethesda, MD 20892 USA. RP Boehm, T (reprint author), Childrens Hosp, Dept Surg, 300 Longwood Ave, Boston, MA 02115 USA. NR 16 TC 50 Z9 55 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0749-503X J9 YEAST JI Yeast PD MAY PY 1999 VL 15 IS 7 BP 563 EP 572 DI 10.1002/(SICI)1097-0061(199905)15:7<563::AID-YEA398>3.0.CO;2-R PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA 196AV UT WOS:000080287600003 PM 10341419 ER PT J AU Pianta, RC Kraft-Sayre, M AF Pianta, RC Kraft-Sayre, M TI Parents' observations about their children's transitions to kindergarten SO YOUNG CHILDREN LA English DT Article C1 NICHHD, Study Early Child Care, Bethesda, MD 20892 USA. Univ Virginia, Natl Ctr Early Dev & Learning Kindergarten Transi, Charlottesville, VA 22903 USA. OI Pianta, Robert/0000-0002-6280-8051 NR 7 TC 12 Z9 12 U1 0 U2 4 PU NATL ASSOC EDUC YOUNG CHILDREN PI WASHINGTON PA 1509 16TH ST., N.W., WASHINGTON, DC 20036-1426 USA SN 0044-0728 J9 YOUNG CHILDREN JI Young Child. PD MAY PY 1999 VL 54 IS 3 BP 47 EP 52 PG 6 WC Education & Educational Research SC Education & Educational Research GA 195DE UT WOS:000080233200010 ER PT J AU Thorn, JM Armstrong, NA Cantrell, LA Kay, BK AF Thorn, JM Armstrong, NA Cantrell, LA Kay, BK TI Identification and characterisation of Xenopus moesin, a Src substrate in Xenopus laevis oocytes SO ZYGOTE LA English DT Article DE actin; cortactin; ERM ID ACTIN-BINDING-SITE; CORTICAL CYTOSKELETON; MEIOTIC MATURATION; EPITHELIAL-CELLS; TUMOR-SUPPRESSOR; MESSENGER-RNAS; C-SRC; EZRIN; PROTEIN; MICROVILLI AB The cortical actin cytoskeleton, consisting of actin filaments and actin binding proteins, immediately underlies the inner surface of the plasma membrane and is important both structurally and in relaying signals from the surface to the interior of the cell. Signal transduction processes, initiated in the cortex, modulate numerous cellular changes ranging from modifications of the local cytoskeleton structure, the position in the cell cycle, to cell behaviour. To examine the molecular mechanisms and events associated with cortical changes. We have investigated targets of the protein tyrosine kinase,Src, which is associated with the cortical cytoskeleton, in Xenopus laevis oocytes. When a mRNA encoding an activated form of Src tyrosine kinase (d-Src) is injected into oocytes several changes are observed: proteins are phosphorylated, the rate at which progesterone matures an oocyte to an egg is accelerated, and the cortex at the site of injection appears to contract. Previous studies have implicated actin filaments in the Src-stimulated cortical rearrangements. In this study we identify two actin binding proteins - cortactin and moesin - as Src substrates in Xenopus oocytes that are Src substrates. We cloned and characterised the cDNA encoding one of those, Xenopus moesin, a member of the ezrin/radixin/moesin (ERM) family of actin binding proteins. In addition, we have determined that moesin is recruited to the cortex at the site of Src mRNA injection. C1 Univ N Carolina, Chapel Hill, NC USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. Univ Wisconsin, Madison, WI USA. RP Thorn, JM (reprint author), NIEHS, POB 12233,Mail Drop F3-04, Res Triangle Pk, NC 27709 USA. NR 51 TC 9 Z9 9 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0967-1994 J9 ZYGOTE JI Zygote PD MAY PY 1999 VL 7 IS 2 BP 113 EP 122 DI 10.1017/S0967199499000465 PG 10 WC Cell Biology; Developmental Biology; Reproductive Biology SC Cell Biology; Developmental Biology; Reproductive Biology GA 244TD UT WOS:000083066100003 PM 10418104 ER PT J AU Metzger, H AF Metzger, H TI It's spring, and thoughts turn to ... allergies SO CELL LA English DT Review ID FC; MECHANISM; CELL C1 NIA, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. RP Metzger, H (reprint author), NIA, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. NR 18 TC 19 Z9 19 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 30 PY 1999 VL 97 IS 3 BP 287 EP 290 DI 10.1016/S0092-8674(00)80738-2 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 192VP UT WOS:000080100500002 PM 10319809 ER PT J AU Hickman, AB Namboodiri, MAA Klein, DC Dyda, F AF Hickman, AB Namboodiri, MAA Klein, DC Dyda, F TI The structural basis of ordered substrate binding by serotonin N-acetyltransferase: Enzyme complex at 1.8 angstrom resolution with a bisubstrate analog SO CELL LA English DT Article ID CATALYTIC MECHANISM; CRYSTAL-STRUCTURES; WATER-MOLECULES; PINEAL-GLAND; REFINEMENT; SUPERFAMILY; PARAMETERS; PROTEINS AB Serotonin N-acetyltransferase, a member of the GNAT acetyltransferase superfamily, is the penultimate enzyme in the conversion of serotonin to melatonin, the circadian neurohormone. Comparison of the structures of the substrate-free enzyme and the complex with a bisubstrate analog, coenzyme A-S-acetyltryptamine, demonstrates that acetyl coenzyme A (AcCoA) binding is accompanied by a large conformational change that in turn leads to the formation of the serotonin-binding site. The structure of the complex also provides insight into how the enzyme may facilitate acetyl transfer. A water-filled channel leading from the active site to the surface provides a pathway for proton removal following amine deprotonation. Furthermore, structural and mutagenesis results indicate an important role for Tyr-168 in catalysis. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Dev Neurobiol Lab, NICHHD, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Physiol, Bethesda, MD 20814 USA. RP Dyda, F (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 37 TC 127 Z9 129 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 30 PY 1999 VL 97 IS 3 BP 361 EP 369 DI 10.1016/S0092-8674(00)80745-X PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 192VP UT WOS:000080100500009 PM 10319816 ER PT J AU Miles, EW Rhee, S Davies, DR AF Miles, EW Rhee, S Davies, DR TI The molecular basis of substrate channeling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID GLUTAMINE PHOSPHORIBOSYLPYROPHOSPHATE AMIDOTRANSFERASE; SYNTHASE ALPHA(2)BETA(2) COMPLEX; REDUCTASE-THYMIDYLATE SYNTHASE; CARBAMOYL-PHOSPHATE SYNTHETASE; GLYCINAMIDE RIBONUCLEOTIDE SYNTHETASE; TRYPTOPHAN SYNTHASE; DIHYDROFOLATE-REDUCTASE; ESCHERICHIA-COLI; ACTIVE-SITES; PHYSIOLOGICAL SIGNIFICANCE C1 NIDDK, Lab Biochem & Genet, Enzyme Struct & Funct Sect, NIH, Bethesda, MD 20892 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Miles, EW (reprint author), NIDDK, Lab Biochem & Genet, Enzyme Struct & Funct Sect, NIH, Bldg 8,Rm 225,8 Ctr Dr MSC 0830, Bethesda, MD 20892 USA. EM EdithM@intra.niddk.nih.gov NR 50 TC 206 Z9 206 U1 4 U2 22 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 APR 30 PY 1999 VL 274 IS 18 BP 12193 EP 12196 DI 10.1074/jbc.274.18.12193 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 192BC UT WOS:000080056800001 PM 10212181 ER PT J AU Togawa, A Morinaga, N Ogasawara, M Moss, J Vaughan, M AF Togawa, A Morinaga, N Ogasawara, M Moss, J Vaughan, M TI Purification and cloning of a brefeldin A-inhibited guanine nucleotide-exchange protein for ADP-ribosylation factors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID YEAST GOLGI-APPARATUS; CHOLERA-TOXIN; HOMOLOGY DOMAINS; PHOSPHOLIPASE-D; SEC7 DOMAIN; ARF; CYTOHESIN-1; PLECKSTRIN; EXPRESSION; TRANSPORT AB Activation of ADP-ribosylation factors (ARFs), similar to 20-kDa guanine nucleotide-binding proteins that play an important role in intracellular vesicular trafficking, depends on guanine nucleotide-exchange proteins (GEPs), which accelerate replacement of bound GDP with GTP. Two major families of ARF GEPs are known: similar to 200-kDa molecules that are inhibited by brefeldin A (BFA), a fungal metabolite that blocks protein secretion and causes apparent disintegration of Golgis structure, and similar to 50-kDa GEPs that are insensitive to BFA. We describe here two human brain cDNAs that encode BFA-inhibited GEPs. One is a similar to 209-kDa protein 99.5% identical in deduced amino acid sequence (1,849 residues) to a BFA-inhibited ARF GEP (p200) from bovine brain. The other smaller protein, which is similar to 74% identical (1,785 amino acids), represents a previously unknown gene. We propose that the former, p200, be named BIG1 for (brefeldin A-inhibited GEP1) and the second, which encodes a similar to 202-kDa protein, BIG2. A protein containing sequences found in BIG2 had been purified earlier from bovine brain. Human tissues contained a 7.5-kilobase BIG1 mRNA and a 9.4-kilobase BIG2 transcript. The BIG1 and BIG2 genes were localized, respectively, to chromosomes 8 and 20, BIG2, synthesized as a His, fusion protein in Sf9 cells, accelerated guanosine 5'-3-O-(thio)triphosphate binding by recombinant ARF1, ARF5, and ARF6, It activated native ARF (mixture of ARF1 and ARF3) more effectively than it did any of the nonmyristoylated recombinant ARFs, BIG2 activity was inhibited by BFA in a concentration-dependent manner but not by B17, a structural analog without effects on Golgi function. Although several clones for similar to 50-kDa BFA-insensitive ARF GEPs are known, these new clones for the similar to 200-kDa BIG1 and BIG2 should facilitate characterization of this rather different family of proteins as well as the elucidation of mechanisms of regulation of BFA-sensitive ARF function in Golgi transport. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Togawa, A (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Rm 5N-307,Bldg 10,10 Ctr Dr,MSC 1434, Bethesda, MD 20892 USA. NR 28 TC 104 Z9 108 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 APR 30 PY 1999 VL 274 IS 18 BP 12308 EP 12315 DI 10.1074/jbc.274.18.12308 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 192BC UT WOS:000080056800020 PM 10212200 ER PT J AU Pacheco-Rodriguez, G Patton, WA Adamik, R Yoo, HS Lee, FJS Zhang, GF Moss, J Vaughan, M AF Pacheco-Rodriguez, G Patton, WA Adamik, R Yoo, HS Lee, FJS Zhang, GF Moss, J Vaughan, M TI Structural elements of ADP-ribosylation factor 1 required for functional interaction with cytohesin-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GUANINE-NUCLEOTIDE-EXCHANGE; GTP-BINDING PROTEIN; SEC7 DOMAIN; CHOLERA-TOXIN; PHOSPHOLIPASE-D; GOLGI-COMPLEX; FACTOR ARNO; ARF GTPASE; ACTIVATION; TRANSPORT AB ADP-ribosylation factor 1 (ARF1) is a 20-kDa guanine nucleotide-binding protein involved in vesicular trafficking. Conversion of inactive ARF-G;DP to active ARF-GTP is catalyzed by guanine nucleotide exchange proteins such as cytohesin-1. Cytohesin-1 and its Sec7 domain (C-1Sec7) exhibit guanine nucleotide exchange protein activity with ARF1 but not ARF-like protein 1 (ARL1), which is 57% identical in amino acid sequence. With chimeric proteins composed of ARF1 (F) and ARL1 (L) sequences we identified three structural elements responsible for this specificity. Cytohesin-1 increased [S-35]guanosine 5'-(gamma-thio)triphosphate binding to L28/F first 28 residues of L, remainder Fl and to a much lesser extent F139L, and mut13F139/L (F139/L with random sequence in the first 13 positions) but not Delta 13ARF1 that lacks the first 13 amino acids; therefore, a nonspecific ARF N terminus was required for cytohesin-1 action. The N terminus was not, however, required for that of C-1Sec7. Both C-1Sec7 and cytohesin-1 effectively released guanosine 5'-(gamma-thio)triphosphate from ARF1, but only C-1Sec7 displaced the nonhydrolyzable GTP analog bound to mut13F139/L, again indicating that structure in addition to the Sec7 domain is involved in cytohesin-1 interaction. Some element(s) of the C-terminal region is also involved, because replacement of the last 42 amino acids with ARL sequence in F139L decreased markedly the interaction with cytohesin-1. Participation of both termini is consistent with the crystallographic structure of ARF in which the two terminal a-helices are in close proximity. ARF1 residues 28-50 are also important in the interaction with cytohesin-1; replacement of Lys-38 with Gin, the corresponding residue in ARL1, abolished the ability to serve as substrate for cytohesin-1 or C-1Sec7. These studies have defined multiple structural elements in ARF1, including switch 1 and the N and C termini, that participate in functional interactions with cytohesin-1 (or its catalytic domain C-1Sec7), which were not apparent from crystallographic analysis. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Pacheco-Rodriguez, G (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Rm 5N-307,Bldg 10,10 Ctr Dr,MSC 1434, Bethesda, MD 20892 USA. OI LEE, FANG-JEN/0000-0002-2167-2426 NR 48 TC 6 Z9 6 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 APR 30 PY 1999 VL 274 IS 18 BP 12438 EP 12444 DI 10.1074/jbc.274.18.12438 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 192BC UT WOS:000080056800038 PM 10212218 ER PT J AU Cociancich, SO Park, SS Fidock, DA Shahabuddin, M AF Cociancich, SO Park, SS Fidock, DA Shahabuddin, M TI Vesicular ATPase-overexpressing cells determine the distribution of malaria parasite oocysts on the midguts of mosquitoes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VACUOLAR H+-ATPASE; B-SUBUNIT; PLASMODIUM-GALLINACEUM; PROTON PUMP; CLONING; TUBULES; FAMILY AB In Plasmodium-infected mosquitoes, oocysts are preferentially located at the posterior half of the posterior midgut, Because mosquitoes rest vertically after feeding, the effect of gravity on the ingested blood has been proposed as the cause of such a biased distribution. In this paper, we examined the oocyst distribution on the midguts of mosquitoes that were continuously rotated to nullify the effect of gravity and found that the typical pattern of oocyst distribution did not change, Invasion of the midgut epithelium by ookinetes was similarly found to be biased toward the posterior part of the posterior midgut, We examined whether the distribution of oocysts depends on the distribution of vesicular ATPase (V-ATPase)-overexpressing cells that Plasmodium ookinetes preferentially use to cross the midgut epithelium. An antiserum raised against recombinant Aedes aegypti V-ATPase B subunit indicated that the majority of VATPase-overexpressing cells in Ae. aegypti and Anopheles gambiae are localized at the posterior part of the posterior midgut, We propose that the typical distribution of oocysts on the mosquito midgut is attributable to the presence and the spatial distribution of the V-ATPase-overexpressing cells in the midgut epithelium. C1 NIAID, Parasit Dis Lab, Malaria Genet Sect, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, Med Entomol Sect, NIH, Bethesda, MD 20892 USA. RP Shahabuddin, M (reprint author), NIAID, Parasit Dis Lab, Malaria Genet Sect, NIH, 9000 Rockville Pike,Bldg 4,Rm B2-39, Bethesda, MD 20892 USA. RI COCIANCICH, Stephane/C-4267-2014; OI COCIANCICH, Stephane/0000-0001-8601-3598; Fidock, David/0000-0001-6753-8938 NR 20 TC 30 Z9 30 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 APR 30 PY 1999 VL 274 IS 18 BP 12650 EP 12655 DI 10.1074/jbc.274.18.12650 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 192BC UT WOS:000080056800065 PM 10212245 ER PT J AU Bai, RL Ewell, JB Nguyen, NY Hamel, E AF Bai, RL Ewell, JB Nguyen, NY Hamel, E TI Direct photoaffinity labeling of cysteine 211 or a nearby amino acid residue of beta-tubulin by guanosine 5 '-diphosphate bound in the exchangeable site SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTP; BINDING; BRAIN AB Tubulin with [8-C-14]GDP bound in the exchangeable site was exposed to ultraviolet light, and radiolabel was cross-linked to two peptide regions of the beta-subunit. Following enrichment for peptides cross-linked to guanosine by boronate chromatography, we confirmed that the cysteine 12 residue was the major site of crosslinking. However, significant radiolabel was also incorporated into a peptide containing amino acid residues 206 through 224. Although every amino acid in this peptide except cysteine 211 was identified by sequential Edman degradation, implying that this was the amino acid residue cross-linked to guanosine, radiolabel at C-8 was usually lost during peptide processing (probably during chromatography at pH 10). Consequently, the radiolabeled amino acid could not be unambiguously identified. C1 NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, NIH, Frederick, MD 21702 USA. US FDA, Ctr Biol Evaluat & Res, Facil Biotechnol Resources, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Drug Discovery Res & Dev,NIH, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick, MD 21702 USA. RP Hamel, E (reprint author), NIH, Lab Drug Discovery Res & Dev, Bldg 37,Rm 5D02,37 Convent Dr, Bethesda, MD 20892 USA. NR 17 TC 10 Z9 10 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 APR 30 PY 1999 VL 274 IS 18 BP 12710 EP 12714 DI 10.1074/jbc.274.18.12710 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 192BC UT WOS:000080056800073 PM 10212253 ER PT J AU Rao, GN Madamanchi, NR Lele, M Gadiparthi, L Gingras, AC Eling, TE Sonenberg, N AF Rao, GN Madamanchi, NR Lele, M Gadiparthi, L Gingras, AC Eling, TE Sonenberg, N TI A potential role for extracellular signal-regulated kinases in prostaglandin F-2 alpha-induced protein synthesis in smooth muscle cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INITIATION-FACTOR 4E; P70 S6 KINASE; INSULIN-RECEPTOR SUBSTRATE-1; PHOSPHATIDYLINOSITOL 3-KINASE; GROWTH-FACTOR; TRANSLATION INITIATION; VENTRICULAR MYOCYTES; CARDIAC-HYPERTROPHY; MESSENGER-RNA; PHAS-I AB To understand the mechanisms of prostaglandin F-2 alpha (PGF(2 alpha))-induced protein synthesis in vascular smooth muscle cells (VSMC), we have studied its effect on two major signal transduction pathways: mitogen-activated protein kinases and phosphatidylinositol 3-kinase (PI3-kinase) and their downstream targets ribosomal protein S6 kinase (p70(S6k)) and eukaryotic initiation factor eIF4E and its regulator 4E-BP1, PGF(2 alpha) induced the activities of extracellular signal-regulated kinase 2 (ERK2) and Jun N-terminal kinase 1 (JNK1) groups of mitogen-activated protein kinases, PI3-kinase, and p70(S6k) in a time-dependent manner in growth-arrested VSMC. PGF(2 alpha) also induced eIF4E and 4E-BP1 phosphorylation, global protein synthesis, and basic fibroblast growth factor-a (bFGF-2) expression in VSMC, Whereas inhibition of PI3-kinase by wortmannin completely blocked the p70(S6k) activation, it only partially decreased the ERK2 activity, and had no significant effect on global protein synthesis and bFGF-2 expression induced by PGF(2 alpha), Rapamycin, a potent inhibitor of p70(S6k), also failed to prevent PGF(2 alpha)-induced global protein synthesis and bFGF-2 expression, although it partially decreased ERK2 activity. In contrast, inhibition of ERK2 activity by PD 098059 led to a significant loss of PGF(2 alpha)-induced eIF4E and 4E-BP1 phosphorylation, global protein synthesis, and bFGF-2 expression. PGF(2 alpha)-induced phosphorylation of eIF4E and 4E-BP1 was also found to be sensitive to inhibition by both wortmannin and rapamycin, These findings demonstrate that 1) PI3-kinase-dependent and independent mechanisms appear to be involved in PGF(2 alpha)-induced activation of ERK2; 2) PGF(2 alpha)-induced eIF4E and 4E-BP1 phosphorylation appear to be mediated by both ERK-dependent and PI3-kinase-dependent rapamycin-sensitive mechanisms; and 3) ERK-dependent eIF4E phosphorylation but not PIS-kinase-dependent p70S6k activation correlates with PGF(2 alpha)-induced global protein synthesis and bFGF-2 expression in VSMC. C1 Univ Texas, Med Branch, Div Cardiol, Galveston, TX 77555 USA. McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Rao, GN (reprint author), Univ Texas, Med Branch, Old John Sealy Hosp 4 124B, 301 Univ Blvd,Route 0567, Galveston, TX 77555 USA. RI Gingras, Anne-Claude/E-9982-2010; OI Gingras, Anne-Claude/0000-0002-6090-4437; Madamanchi, Nageswara/0000-0003-0590-0908 NR 59 TC 44 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 APR 30 PY 1999 VL 274 IS 18 BP 12925 EP 12932 DI 10.1074/jbc.274.18.12925 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 192BC UT WOS:000080056800103 PM 10212283 ER PT J AU Munoz, A Petering, DH Shaw, CF AF Munoz, A Petering, DH Shaw, CF TI Structure-reactivity relationships among one modified and the two synthetic native domains of lobster metallothionein SO JOURNAL OF INORGANIC BIOCHEMISTRY LA English DT Meeting Abstract C1 Univ Wisconsin, Dept Chem, Milwaukee, WI 53201 USA. Univ Wisconsin, NIEHS, Marine & Freshwater Biomed Core Ctr, Milwaukee, WI 53201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0162-0134 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD APR 30 PY 1999 VL 74 IS 1-4 BP 241 EP 241 PG 1 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 211JP UT WOS:000081157700455 ER PT J AU Munoz, A Petering, DH Shaw, CF AF Munoz, A Petering, DH Shaw, CF TI Reversed differential reactivity of the domains of mammalian metallothioneins SO JOURNAL OF INORGANIC BIOCHEMISTRY LA English DT Meeting Abstract C1 Univ Wisconsin, Dept Chem, Milwaukee, WI 53201 USA. Univ Wisconsin, UWM, NIEHS, Marine & Freshwater Biomed Core Ctr, Milwaukee, WI 53201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0162-0134 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD APR 30 PY 1999 VL 74 IS 1-4 BP 294 EP 294 PG 1 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 211JP UT WOS:000081157700548 ER PT J AU van Spaendonk, RML McConkey, GA Ramesar, J Gabrielian, A McCutchan, TF Janse, CJ Waters, AP AF van Spaendonk, RML McConkey, GA Ramesar, J Gabrielian, A McCutchan, TF Janse, CJ Waters, AP TI Identification of the transcription initiation site of the asexually expressed rRNA genes of the malaria parasite Plasmodium berghei SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE malaria; Plasmodium berghei; ribosomal RNA; transcription ID RIBOSOMAL-RNA GENES; POLYMERASE-I; NUCLEOTIDE-SEQUENCE; STRUCTURAL FEATURES; DNA; FALCIPARUM; PROMOTERS; DISTINCT; UPSTREAM; PROTEIN AB The start site of the A-type ribosomal RNA transcription units of the rodent malaria parasite, Plasmodium berghei, has been identified. The two A-type units cannot be distinguished within the transcription unit, yet exist as single copies on different chromosomes. Gene transcription initiates 820 bp upstream of the A-type small subunit (SSU) ribosomal gene and two major processing sites were mapped 610 and 611 nucleotides upstream of the SSU in the external transcribed spacer region. Surprisingly the nucleotide sequence of the DNA region containing the putative ribosomal promoter lacked repetitive DNA sequences typical of ribosomal promoters. This region was further analysed by computer using programs designed to reveal sequence-dependent structural features. Comparison of DNA curvature, duplex stability and pattern of twist angle variation revealed a striking degree of conservation between the ribosomal promoters from Plasmodium and other eukaryotes. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Leiden Univ, Dept Parasitol, NL-2300 RC Leiden, Netherlands. NIAID, Growth & Dev Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIH, Computat Biol Branch, NCBI, NLM, Bethesda, MD 20892 USA. RP Waters, AP (reprint author), Leiden Univ, Dept Parasitol, Postbus 9605, NL-2300 RC Leiden, Netherlands. RI Waters, Andy/C-9377-2009 OI Waters, Andy/0000-0001-8900-2982 NR 38 TC 4 Z9 4 U1 0 U2 1 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 30 PY 1999 VL 99 IS 2 BP 193 EP 205 DI 10.1016/S0166-6851(99)00016-X PG 13 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 194XT UT WOS:000080220600004 PM 10340484 ER PT J AU Guidotti, LG Rochford, R Chung, J Shapiro, M Purcell, R Chisari, FV AF Guidotti, LG Rochford, R Chung, J Shapiro, M Purcell, R Chisari, FV TI Viral clearance without destruction of infected cells during acute HBV infection SO SCIENCE LA English DT Article ID HEPATITIS-B VIRUS; TRANSGENIC MICE; INTRACELLULAR INACTIVATION; T-CELLS; HEPATOCYTE; RECOVERY; CHIMPANZEES; REPLICATION; EXPRESSION; THERAPY AB Viral clearance during hepatitis B virus (HBV) infection has been thought to reflect the destruction of infected hepatocytes by CD8(+) T lymphocytes. However, in this study, HBV DNA was shown to Largely disappear from the Liver and the blood of acutely infected chimpanzees Long before the peak of T cell infiltration and most of the Liver disease. These results demonstrate that noncytopathic antiviral mechanisms contribute to viral clearance during acute viral hepatitis by purging HBV replicative intermediates from the cytoplasm and covalently closed circular viral DNA from the nucleus of infected cells. C1 Scripps Res Inst, Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. Bioqual Inc, Rockville, MD 20850 USA. NIH, Bethesda, MD 20892 USA. RP Chisari, FV (reprint author), Scripps Res Inst, Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. RI Chisari, Francis/A-3086-2008; OI Guidotti, Luca G./0000-0002-0205-2678; Chisari, Francis/0000-0002-4832-1044 FU NCI NIH HHS [R37 CA40489]; NIAID NIH HHS [R01 AI20001, R01 AI40696] NR 25 TC 765 Z9 840 U1 4 U2 23 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 APR 30 PY 1999 VL 284 IS 5415 BP 825 EP 829 DI 10.1126/science.284.5415.825 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 192AW UT WOS:000080056200053 PM 10221919 ER PT J AU Collet, X Francone, O Besnard, F Fielding, CJ AF Collet, X Francone, O Besnard, F Fielding, CJ TI Secretion of lecithin : cholesterol acyltransferase by brain neuroglial cell lines SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE LCAT; nerve cells ID DENSITY LIPOPROTEIN RECEPTOR; APOLIPOPROTEIN-D; MESSENGER-RNA; HUMAN-PLASMA; INSITU HYBRIDIZATION; NERVOUS-SYSTEM; EXPRESSION; PROTEIN; CDNA; LOCALIZATION AB The ability of different human and rat brain cell lines (neuronal and gliomal) to secrete lecithin:cholesterol acyltransferase (LCAT) was examined. Of these, the strongly secreting human gliomal (U343 and U251) cell lines were selected for a detailed study of enzymatic and structural properties of the secreted LCAT. Both plasma- and brain-derived enzymes are inhibited by DTNB (90%) and are activated by apolipoprotein A-I. LCAT mRNA was measured in these cell lines at levels similar to that found in HepG2 cells. In contrast, apoA-I, apoE, and apoD mRNAs were undetectable in these cell lines. The presence of functional LCAT secreted by cultured nerve cells provides an in vitro model to study the expression and function of LCAT in the absence of others factors of plasma cholesterol metabolism. (C) 1999 Academic Press. C1 Univ Calif San Francisco, Med Ctr, Cardiovasc Res Inst, San Francisco, CA 94143 USA. Hop Purpan, U326, INSERM, F-31059 Toulouse, France. Univ Calif San Francisco, Med Ctr, Dept Physiol, San Francisco, CA 94143 USA. NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Collet, X (reprint author), Univ Calif San Francisco, Med Ctr, Cardiovasc Res Inst, San Francisco, CA 94143 USA. NR 31 TC 14 Z9 16 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 APR 29 PY 1999 VL 258 IS 1 BP 73 EP 76 DI 10.1006/bbrc.1999.0601 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 192BT UT WOS:000080058800014 PM 10222237 ER PT J AU Permana, PA Luczy-Bachman, G Bogardus, C AF Permana, PA Luczy-Bachman, G Bogardus, C TI Protein targeting to glycogen/PPP1R5: Screening of coding and flanking genomic regions for polymorphisms and association analysis with insulin action in Pima Indians SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PHOSPHATASE; RESISTANCE; MUSCLE; NIDDM; GENE; SEQUENCE; SUBUNIT; LINKAGE AB Insulin resistance, a major predictor of type 2 diabetes mellitus, is genetically inherited in Pima Indians, a population with a high prevalence of the metabolically complex disease. Protein targeting to glycogen/PPP1R5 has recently been identified as a potential regulator of glycogen synthase, the rate-limiting enzyme of the insulin-induced glycogenesis. The gene is located on chromosome 10q23-24, where there is a suggestive linkage to insulin action in this population, establishing it as a functional and positional candidate gene. In this study, we discovered 2 novel polymorphisms upstream of the 5'UTR of the gene, with only one found in Pima Indians, but no polymorphism in the coding sequence. The genotype frequencies of the polymorphism and transcript levels of the gene in skeletal muscle do not correlate with insulin action in the subjects. These results exclude any significant role of protein targeting to glycogen/PPP1R5 in insulin resistance in Pima Indians. (C) 1999 Academic Press. C1 NIDDKD, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA. RP Permana, PA (reprint author), NIDDKD, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Clin Res Branch, NIH, 4212 N 16Th St, Phoenix, AZ 85016 USA. NR 19 TC 6 Z9 7 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 APR 29 PY 1999 VL 258 IS 1 BP 184 EP 186 DI 10.1006/bbrc.1999.0614 PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 192BT UT WOS:000080058800034 PM 10222257 ER PT J AU Stefanski, R Ladenheim, B Lee, SH Cadet, JL Goldberg, SR AF Stefanski, R Ladenheim, B Lee, SH Cadet, JL Goldberg, SR TI Neuroadaptations in the dopaminergic system after active self-administration but not after passive administration of methamphetamine SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE methamphetamine; self-administration; neuroadaptation; dopamine; dopamine transporter; dopamine D-1 receptor; dopamine D-2 receptor ID VENTRAL TEGMENTAL AREA; FREELY MOVING RATS; AMPHETAMINE PREFERENTIALLY INCREASE; NUCLEUS-ACCUMBENS; EXTRACELLULAR DOPAMINE; SUBSTANTIA-NIGRA; INVIVO MICRODIALYSIS; PHARMACOLOGICAL RESPONSIVENESS; AUTORECEPTOR SUBSENSITIVITY; INDUCED RELEASE AB Methamphetamine is a strong and long-lasting stimulant that can be easily synthesized and is effective when taken either orally, intravenously, or smoked as 'ice'. Due to it's escalating abuse, a clear need exists for laboratory procedures to evaluate motivational components of methamphetamine abuse and their underlying neurobiological mechanisms. In the present experiment, we utilized a 'yoked' procedure in which rats were run simultaneously in groups of three, with two rats serving as yoked controls which received an injection of either 0.1 mg/kg methamphetamine or saline which was not contingent on responding each time a response-contingent injection of 0.1 mg/kg methamphetamine was self-administered by the third paired rat. Rats that had actively self-administered methamphetamine for 5 weeks and were then withdrawn from methamphetamine for 24 h showed marked decreases in somatodendritic dopamine D-2 autoreceptors levels in the ventral tegmental area (34%) and medial (31%) and dorsal (21%) part of the substantia nigra zona compacta with a corresponding down-regulation of dopamine D-1 receptors in the shell of the nucleus accumbens (15%), as measured by in vitro quantitative autoradiography. Since the decreases in levels of dopamine D-1 and D-2 receptors which occurred in rats self-administering methamphetamine did not occur in littermates that received either yoked injections of methamphetamine or saline, these changes likely reflect motivational states that were present when methamphetamine injection depended an active drug self-administration behavior. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NIDA, Preclin Pharmacol Lab, NIH, Intramural Res Program, Baltimore, MD 21224 USA. NIDA, Mol Neuropsychiat Sect, NIH, Intramural Res Program, Baltimore, MD 21224 USA. RP Goldberg, SR (reprint author), NIDA, Preclin Pharmacol Lab, NIH, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 53 TC 90 Z9 92 U1 1 U2 3 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 APR 29 PY 1999 VL 371 IS 2-3 BP 123 EP 135 DI 10.1016/S0014-2999(99)00094-1 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 194TH UT WOS:000080209300003 PM 10357249 ER PT J AU Takeuchi, O Kawai, T Sanjo, H Copeland, NG Gilbert, DJ Jenkins, NA Takeda, K Akira, S AF Takeuchi, O Kawai, T Sanjo, H Copeland, NG Gilbert, DJ Jenkins, NA Takeda, K Akira, S TI TLR6: A novel member of an expanding Toll-like receptor family SO GENE LA English DT Article DE JNK; NF-kappa B; toll-like receptor family ID DROSOPHILA TOLL; PROTEIN; KINASE; MYD88; IRAK; ORGANIZATION; ACTIVATION; IMMUNITY; PATHWAYS; ADAPTER AB Drosophila Toll protein is shown to activate the innate immune system in adult and regulate the dorsoventral patterning in the developing embryo. Recently, five human homologs of Drosophila Toll, designated as Toll-like receptors (TLRs), have been identified and shown to play a role in the innate immune response. We report here the molecular cloning and characterization of a new member of Toll-like receptor family, Toll-like receptor 6 (TLR6). Human and murine TLR6 are type-I transmembrane receptors that contain both an extracellular leucine-rich repeat (LRR) domain and a cytoplasmic Toll/IL-1 receptor (IL-1R)-like region. The amino acid sequence of human TLR6 (hTLR6) is most similar to that of hTLR1 with 69% identity. RT-PCR analysis revealed that murine TLR6 is expressed predominantly in spleen, thymus, ovary and lung. Like other TLR family members, constitutively active TLR6 activates both NF-kappa B and c-Jun N-terminal kinase (JNK). The TLR6 gene, as well as the TLR1 gene, mapped to the proximal region of murine chromosome 5 within 1.7 cM of each other. These results suggest that TLR6 is a novel member of an expanding TLR family. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Hyogo Coll Med, Dept Biochem, Nishinomiya, Hyogo 6638501, Japan. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab,Frederick Canc Program, Frederick, MD 21702 USA. RP Akira, S (reprint author), Hyogo Coll Med, Dept Biochem, 1-1 Mukogawa Cho, Nishinomiya, Hyogo 6638501, Japan. RI Akira, Shizuo/C-3134-2009; Takeda, Kiyoshi/C-9331-2009; Takeuchi, Osamu/D-6007-2011 NR 22 TC 301 Z9 317 U1 5 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD APR 29 PY 1999 VL 231 IS 1-2 BP 59 EP 65 DI 10.1016/S0378-1119(99)00098-0 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 196VA UT WOS:000080327200007 PM 10231569 ER PT J AU Zhang, ZJ Mandal, AK Wang, N Keck, CL Zimonjic, DB Popescu, NC Mukherjee, AB AF Zhang, ZJ Mandal, AK Wang, N Keck, CL Zimonjic, DB Popescu, NC Mukherjee, AB TI Palmitoyl-protein thioesterase gene expression in the developing mouse brain and retina: Implications for early loss of vision in infantile neuronal ceroid lipofuscinosis SO GENE LA English DT Article DE Batten disease; cDNA cloning; lysosomal storage; neurodegenerative disease; palmitoyl-protein thioesterase ID MYELIN PROTEOLIPID PROTEIN; MOLECULAR-CLONING; ACYLATION; PATHOGENESIS; CHROMOSOMES; DEFICIENCY; ASSIGNMENT; MUTATIONS; VARIANT; MAPS AB Mutations in the palmitoyl-protein thioesterase (PPT) gene cause infantile neuronal ceroid lipofuscinosis (INCL), the clinical manifestations of which include the early loss of vision followed by deterioration of brain functions. To gain insight into the temporal onset of these clinical manifestations, we isolated and characterized a murine PPT (mPPT)-cDNA, mapped the gene on distal chromosome 4, and studied its expression in the eye and in the brain during development. Our results show that both cDNA and protein sequences of the murine and human PPTs are virtually identical and that the mPPT expression in the retina and in the brain is temporally regulated during development. Furthermore, the retinal expression of mPPT occurs much earlier and at a higher level than in the brain at all developmental stages investigated. Since many retinal and brain proteins are highly palmitoylated and depalmitoylation by PPT is essential for their effective recycling in the lysosomes, our results raise the possibility that inactivating mutations of the PPT gene, as occur in INCL, are likely to cause cellular accumulation of lipid-modified proteins in the retina earlier than in the brain. Consequently, the loss of vision occurs before the deterioration of brain functions in this disease. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NICHD, Heritable Disorders Branch, Sect Dev Genet, NIH, Bethesda, MD 20892 USA. NCI, Mol Cytogenet Sect, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Mukherjee, AB (reprint author), NICHD, Heritable Disorders Branch, Sect Dev Genet, NIH, Bethesda, MD 20892 USA. NR 32 TC 8 Z9 9 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 APR 29 PY 1999 VL 231 IS 1-2 BP 203 EP 211 DI 10.1016/S0378-1119(99)00050-5 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 196VA UT WOS:000080327200023 PM 10231585 ER PT J AU Lippincott-Schwartz, J AF Lippincott-Schwartz, J TI Cell biology - Coated-pit dynamics SO NATURE LA English DT Editorial Material C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Lippincott-Schwartz, J (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, 18 Lib Dr, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 29 PY 1999 VL 398 IS 6730 BP 753 EP 753 DI 10.1038/19632 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 192BL UT WOS:000080058100026 PM 10235254 ER PT J AU Masur, H Kaplan, J AF Masur, H Kaplan, J TI Does Pneumocystis carinii prophylaxis still need to be lifelong? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PNEUMONIA; RISK C1 NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. RP Masur, H (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 10 TC 12 Z9 12 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 29 PY 1999 VL 340 IS 17 BP 1356 EP 1358 DI 10.1056/NEJM199904293401709 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 191BQ UT WOS:000080001700009 PM 10219072 ER PT J AU Harari, D Tzahar, E Romano, J Shelly, M Pierce, JH Andrews, GC Yarden, Y AF Harari, D Tzahar, E Romano, J Shelly, M Pierce, JH Andrews, GC Yarden, Y TI Neuregulin-4: a novel growth factor that acts through the ErbB-4 receptor tyrosine kinase SO ONCOGENE LA English DT Article DE growth factor; oncogene; pancreas; signal transduction; tyrosine kinase ID NEU DIFFERENTIATION FACTOR; SIGNAL-TRANSDUCTION; CARDIAC DEVELOPMENT; CELLULAR-RESPONSE; FACTOR FAMILY; EGF DOMAIN; HEREGULIN; LIGAND; BINDING; ACTIVATION AB The ErbB/HER family of receptor tyrosine kinases consists of four receptors that bind a large number of growth factor ligands sharing an epidermal growth factor- (EGF)-like motif, Whereas ErbB-1 binds seven different ligands whose prototype is EGF, the three families of neuregulins (NRGs) activate ErbB-3 and/or ErbB-4. Here we characterize a fourth neuregulin, NRG-4, that acts through ErbB-4. The predicted pro-NRG-4 is a transmembrane protein carrying a unique EGF-like motif and a short cytoplasmic domain. A synthetic peptide encompassing the full-length EGF-like domain can induce growth of interleukin-dependent cells ectopically expressing ErbB-4, but not cells expressing the other three ErbB proteins or their combinations. Consistent with specificity to ErbB-4, NRG-4 can displace an ErbB-4-bound NRG-1 and can activate signaling downstream of this receptor, Expression of NRG-4 mRNA was detected in the adult pancreas and weakly in muscle; other tissues displayed no detectable NRG-4 mRNA. The primary structure and the pattern of expression of NRG-4, together with the strict specificity of this growth factor to ErbB-4, suggest a physiological role distinct from that of the known ErbB ligands. C1 Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel. NCI, Bethesda, MD 20892 USA. Pfizer Inc, Cent Res, Groton, CT 06340 USA. RP Yarden, Y (reprint author), Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel. RI YARDEN, YOSEF/K-1467-2012 NR 60 TC 178 Z9 183 U1 0 U2 5 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 29 PY 1999 VL 18 IS 17 BP 2681 EP 2689 DI 10.1038/sj.onc.1202631 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 193FH UT WOS:000080124900003 PM 10348342 ER PT J AU Hamel, E Sackett, DL Vourloumis, D Nicolaou, KC AF Hamel, E Sackett, DL Vourloumis, D Nicolaou, KC TI The coral-derived natural products eleutherobin and sarcodictyins A and B: Effects on the assembly of purified tubulin with and without microtubule-associated proteins and binding at the polymer taxoid site SO BIOCHEMISTRY LA English DT Article ID PACLITAXEL TAXOL; BIOLOGICAL-ACTIVITY; STABILIZING AGENTS; ELEUTHOSIDE-A; RESISTANT; CELLS; ANALOGS; DISCODERMOLIDE; EPOTHILONES; NUCLEATION AB We examined interactions with purified tubulin of synthetic sarcodictyins A and B and eleutherobin (coral-derived antimitotic agents) and of compound 1, an analogue of sarcodictyin A methylated at the C-3 oxygen atom (i.e., the methyl ketal analogue of sarcodictyin A and thus structurally similar to eleutherobin but lacking the C-3 sugar moiety). Eleutherobin was much more active than sarcodictyins A and B, which were somewhat more active than compound 1, Effects of eleutherobin did not differ greatly from those of paclitaxel and epothilone A. Eleutherobin and epothilone A were competitive inhibitors of the binding of radiolabeled paclitaxel to tubulin polymer (apparent K-i values of 2.1 and 2.6 mu M, respectively). Tubulin assembly reactions induced by all compounds were similar to the paclitaxel-driven reactions in being enhanced by the addition of microtubule-associated proteins and/or GTP to the reaction mixture and by progressively higher reaction temperatures. Antiproliferative activity was studied in six human cancer cell lines, including two paclitaxel-resistant lines with point mutations in a beta-tubulin gene. Except for compound 1, effects on cell growth were generally in accord with effects on purified tubulin. Thus, sarcodictyins A and B had IC50 values in the 200-500 nM range; paclitaxel, <10 nM (except in the resistant lines); and eleutherobin and epothilone A, 10-40 nM. The antiproliferative activity of compound 1 was more comparable to that of eleutherobin than sarcodictyin A, despite its weak interaction with tubulin, The activities of the sarcodictyins, eleutherobin, and compound 1 in the mutant ovarian lines were similar to their activities in the parental line. C1 NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. RP Nicolaou, KC (reprint author), NIH, Bldg 37,Room 5D02, Bethesda, MD 20892 USA. NR 38 TC 114 Z9 123 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 27 PY 1999 VL 38 IS 17 BP 5490 EP 5498 DI 10.1021/bi983023n PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 193YM UT WOS:000080165400024 PM 10220336 ER PT J AU Yarden, RI Brody, LC AF Yarden, RI Brody, LC TI BRCA1 interacts with components of the histone deacetylase complex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; RNA-POLYMERASE-II; OVARIAN-CANCER; BREAST-CANCER; DNA-DAMAGE; IN-VIVO; TRANSCRIPTIONAL ACTIVATION; REPRESS TRANSCRIPTION; CHROMATIN STRUCTURE; NEGATIVE REGULATOR AB Germ-line mutations in the BRCA1 tumor-suppressor gene are associated with an increased susceptibility to breast and ovarian cancer. BRCA1 contains a carboxyl-terminal domain (BRCT) that is shared with several other proteins involved in maintaining genome integrity. In an effort to understand the function of BRCA1, me sought to isolate proteins that interact with the BRCT domain. Purified BRCT polypeptide was used as a probe to screen a human placenta cDNA expression library by Far Western analysis. Here we report that BRCA1 interacts in vivo and in vitro with the Rb-binding proteins, RbAp46 and RbAp48, as well as with Rb. Moreover, the BRCT domain associates with the histone deacetylases HDAC1 and HDAC2. These results demonstrate that BRCA1 interacts with components of the histone deacetylase complex, and therefore may explain the involvement of BRCA1 in multiple processes such as transcription, DNA repair, and recombination. C1 Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Brody, LC (reprint author), Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, 49 Convent Dr,Room 3A14, Bethesda, MD 20892 USA. NR 57 TC 237 Z9 245 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 27 PY 1999 VL 96 IS 9 BP 4983 EP 4988 DI 10.1073/pnas.96.9.4983 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 193HQ UT WOS:000080130200047 PM 10220405 ER PT J AU Bulger, M von Doorninck, JH Saitoh, N Telling, A Farrell, C Bender, MA Felsenfeld, G Axel, R Groudine, M AF Bulger, M von Doorninck, JH Saitoh, N Telling, A Farrell, C Bender, MA Felsenfeld, G Axel, R Groudine, M TI Conservation of sequence and structure flanking the mouse and human beta-globin loci: The beta-globin genes are embedded within an array of odorant receptor genes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID OPEN CHROMATIN STRUCTURE; CONTROL REGION; ALPHA/DELTA LOCUS; OLFACTORY EPITHELIUM; ERYTHROID-CELLS; MOLECULAR-BASIS; GERM-CELLS; EXPRESSION; DOMAIN; ORGANIZATION AB In mouse and human, the beta-globin genes reside in a linear array that is associated with a positive regulatory element located 5' to the genes known as the locus control region (LCR), The sequences of the mouse and human beta-globin LCRs are homologous, indicating conservation of an essential function in beta-globin gene regulation. We have sequenced regions flanking the beta-globin locus in both mouse and human and found that homology associated with the LCR is more extensive than previously known, making up a conserved block of approximate to 40 kb. In addition, we have identified DNaseI-hypersensitive sites within the newly sequenced regions in both mouse and human, and these structural features also are conserved. Finally, we have found that both mouse and human beta-globin loci are embedded within an array of odorant receptor genes that are expressed in olfactory epithelium, and we also identify an olfactory receptor gene located 3' of the beta-globin locus in chicken. The data demonstrate an evolutionarily conserved genomic organization for the beta-globin locus and suggest a possible role for the beta-globin LCR in control of expression of these odorant receptor genes and/or the presence of mechanisms to separate regulatory signals in different tissues, C1 Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA. Columbia Univ Coll Phys & Surg, Howard Hughes Med Inst, Ctr Neurobiol & Behav, New York, NY 10032 USA. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Washington, Sch Med, Dept Radiat Oncol, Seattle, WA 98195 USA. RP Bulger, M (reprint author), Fred Hutchinson Canc Res Ctr, Div Basic Sci, 1100 Fairview Ave N, Seattle, WA 98109 USA. FU NIDDK NIH HHS [DK44746, DK52854, R37 DK044746] NR 39 TC 113 Z9 118 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 APR 27 PY 1999 VL 96 IS 9 BP 5129 EP 5134 DI 10.1073/pnas.96.9.5129 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 193HQ UT WOS:000080130200072 PM 10220430 ER PT J AU Liu, KB Schoonmaker, MM Levine, BL June, CH Hodes, RJ Weng, NP AF Liu, KB Schoonmaker, MM Levine, BL June, CH Hodes, RJ Weng, NP TI Constitutive and regulated expression of telomerase reverse transcriptase (hTERT) in human lymphocytes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CATALYTIC SUBUNIT GENE; NORMAL HUMAN-CELLS; HUMAN FIBROBLASTS; ANTIGEN RECEPTOR; RNA COMPONENT; B-LYMPHOCYTES; LIFE-SPAN; IN-VITRO; T-CELLS; ACTIVATION AB Human telomerase consists of two essential components, telomerase RNA template (hTER) and telomerase reverse transcriptase (hTERT), and functions to synthesize telomere repeats that serve to protect the integrity of chromosomes and to prolong the replicative life span of cells. Telomerase activity is expressed selectively in germ-line and malignant tumor cells but not in most normal human somatic cells. As a notable exception, telomerase is expressed in human lymphocytes during development, differentiation, and activation. Recent studies have suggested that regulation of telomerase is determined by transcription of hTERT but not hTER. The highly regulated expression of telomerase in lymphocytes provides an opportunity to analyze the contribution of transcriptional regulation of hTERT and hTER. We report here an analysis of hTERT expression by Northern and ill situ hybridization. It was found that hTERT mRNA is expressed at detectable levels in all subsets of human lymphocytes isolated from thymus, tonsil, and peripheral blood, regardless of the status of telomerase activity. hTERT expression is regulated as a function of lineage development, differentiation, and activation. Strikingly, however, telomerase activity in these cells is not correlated strictly with the levels of hTERT and hTER transcripts. The absence of correlation between telomerase activity and hTERT mRNA could not be attributed to the presence of hTERT splice variants or to detectable inhibitors of telomerase activity. Thus, transcriptional regulation of hTERT is not sufficient to account for telomerase activity in human lymphocytes, indicating a likely role of posttranscriptional factors in the control of enzyme function. C1 NIA, Immunol Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Us Mil HIV Res Program, Henry M Jackson Fdn Advancement Mil Med, Bethesda, MD 20889 USA. NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. NIA, NIH, Bethesda, MD 20892 USA. RP Liu, KB (reprint author), NIA, Immunol Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RI Levine, Bruce/D-1688-2009; OI Liu, Kebin/0000-0003-1965-7240 NR 35 TC 177 Z9 194 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 APR 27 PY 1999 VL 96 IS 9 BP 5147 EP 5152 DI 10.1073/pnas.96.9.5147 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 193HQ UT WOS:000080130200075 PM 10220433 ER PT J AU Zhang, ZQ Schuler, T Cavert, W Notermans, DW Gebhard, K Henry, K Havlir, DV Gunthard, HF Wong, JK Little, S Feinberg, MB Polis, MA Schrager, LK Schacker, TW Richman, DD Corey, L Danner, SA Haase, AT AF Zhang, ZQ Schuler, T Cavert, W Notermans, DW Gebhard, K Henry, K Havlir, DV Gunthard, HF Wong, JK Little, S Feinberg, MB Polis, MA Schrager, LK Schacker, TW Richman, DD Corey, L Danner, SA Haase, AT TI Reversibility of the pathological changes in the follicular dendritic cell network with treatment of HIV-1 infection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL THERAPY; LYMPHOID-TISSUES; T-CELL; KINETICS; BLOOD; MICE AB Over the course of HIV-1 infection, the lymphoid follicles where the humoral immune response is generated initially increase in size and number and then progressively involute. In advanced disease, the network of the processes of follicular dendritic cells (FDCs) that serve as antigen repositories and anatomical substrate for B and T cells and antigen to interact is destroyed, contributing to the breakdown of the immune system. Because destruction of FDCs is associated with deposition of HIV-1, and much of the virus can be cleared from the network with antiretroviral therapy, we investigated the reversibility of damage. We measured the immunohistochemically stainable FDC compartment by quantitative image analysis, and we documented changes in this compartment at different stages of disease. We show that treatment, initiated even at advanced stages of HIV-1 disease, can slowly reverse pathological changes in the FDC network. C1 Univ Minnesota, Sch Med, Dept Microbiol, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA. Univ Amsterdam, Acad Med Ctr, Div Infect Dis Trop Med & AIDS, NL-1100 DE Amsterdam, Netherlands. Univ Amsterdam, Acad Med Ctr, Natl AIDS Therapy Evaluat Ctr, NL-1100 DE Amsterdam, Netherlands. Reg Hosp, HIV Program, St Paul, MN 55101 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. San Diego Vet Affairs Med Ctr, La Jolla, CA 92093 USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Univ Washington, Pacific Med Ctr, Dept Lab Med & Microbiol, Seattle, WA USA. RP Haase, AT (reprint author), Univ Minnesota, Sch Med, Dept Microbiol, 420 Delaware St SE, Minneapolis, MN 55455 USA. RI gunthard, huldrych/F-1724-2011; OI gunthard, huldrych/0000-0002-1142-6723; Polis, Michael/0000-0002-9151-2268 FU NIAID NIH HHS [AI 36214, AI 27670, AI 38858, P30 AI036214, R37 AI028246, R37 AI029164, U01 AI027670, U01 AI038858] NR 13 TC 53 Z9 54 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 27 PY 1999 VL 96 IS 9 BP 5169 EP 5172 DI 10.1073/pnas.96.9.5169 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 193HQ UT WOS:000080130200079 PM 10220437 ER PT J AU Pozsgay, V Chu, CY Pannell, L Wolfe, J Robbins, JB Schneerson, R AF Pozsgay, V Chu, CY Pannell, L Wolfe, J Robbins, JB Schneerson, R TI Protein conjugates of synthetic saccharides elicit higher levels of serum IgG lipopolysaccharide antibodies in mice than do those of the O-specific polysaccharide from Shigella dysenteriae type 1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INFLUENZAE TYPE-B; HEMOLYTIC-UREMIC SYNDROME; ESCHERICHIA-COLI; CHAIN-LENGTH; VACCINES; IMMUNOGENICITY; TOXIN; ANTIGEN; OLIGOSACCHARIDES; SPECTROSCOPY AB Our development of vaccines to prevent shigellosis is based on the hypothesis that a critical (protective) level of serum IgG to the O-specific polysaccharide (O-SP) domain of Shigella lipopolysaccharide (LPS) confers immunity. The O-SP is a hapten and must be conjugated to a protein to induce serum antibodies. The O-SP of Shigella dysenteriae type 1 (approximate to 27 tetrasaccharide repeat units), prepared by acid hydrolysis of the LPS, was bound to human serum albumin (HSA) by multiple point attachment (O-SP-HSA): The molar ratio of HSA to O-SP was 1.0, Synthetic saccharides, composed of one or multiples of the O-SP tetrasaccharide, equipped with a spacer at their reducing end, were bound to HSA by a single point attachment: The average molar ratios of the saccharides to HSA ranged from 4 to 24, Serum IgG anti-LPS, elicited in mice by O-SP-HSA or synthetic tetra-, octa-, dodeca-, and hexadecasaccharide fragments, was measured by ELISA, Outbred 6-week-old female mice were injected s.c. three times at biweekly intervals with 2.5 mu g of saccharide as a conjugate and were bled 7 days after the second and third injections. Excepting the tetramer, conjugates of the octamer, dodecamer and hexadecamer elicited IgG LPS antibodies after the second injection, a statistically significant rise (booster) after the third injection, and higher levels than those vaccinated with O-SP-HSA (P = 0.0001). The highest geometric mean levels of IgG anti-LPS were elicited by the hexadecamer with 9 chains or 9 moles of saccharide/HSA (15.5 ELISA units) followed by the octamer with 20 chains (11.1 ELISA units) and the dodecamer with 10 chains (9.52 ELISA units). Clinical evaluation of these synthetic saccharides bound to a medically useful carrier is planned. C1 NICHHD, Dev & Mol Immun Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Unit Mass Spect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Pozsgay, V (reprint author), NICHHD, Dev & Mol Immun Lab, NIH, Bldg 6,Room 424, Bethesda, MD 20892 USA. NR 40 TC 121 Z9 123 U1 1 U2 6 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 APR 27 PY 1999 VL 96 IS 9 BP 5194 EP 5197 DI 10.1073/pnas.96.9.5194 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 193HQ UT WOS:000080130200084 PM 10220442 ER PT J AU Kligerman, AD Erexson, GL AF Kligerman, AD Erexson, GL TI An evaluation of the feasibility of using cytogenetic damage as a biomarker for alachlor exposure SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE alachlor; herbicide; blood lymphocyte ID COMMERCIAL PESTICIDE APPLICATORS; CULTURED HUMAN-LYMPHOCYTES; DNA ADDUCT FORMATION; HERBICIDES ALACHLOR; X-RADIATION; METABOLITES; MICRONUCLEI; 2-CHLORO-N-(2,6-DIETHYLPHENYL)ACETAMIDE; GENOTOXICITY; CELLS AB Alachlor is a widely used herbicide for which there is significant human exposure, principally through groundwater contamination and inhalation. Because alachlor is purported to be carcinogenic and mutagenic, we initiated studies to determine if induced cytogenetic damage could be used as a biomarker for exposure to this herbicide. Both isolated and whole blood human lymphocytes were exposed to alachlor using several protocols. The lymphocytes were cultured for analysis of sister chromatid exchange (SCE), chromosome aberrations (CAs), micronuclei (MN) in cytochalasin B-induced binucleated cells, and proliferation kinetics using the replicative index (RT). In addition, CD rats were injected with either 10 or 50 mg kg(-1) of alachlor, 2-chloro-N-(2,6-diethylphenyl) acetamide (CDEPA) or 2,6-diethylanaline (DEA). After 24 h, the peripheral blood lymphocytes were removed and cultured for SCE and RI analysis. Alachlor did induce a concentration-related increase in SCE in vitro, but neither it nor its metabolites (CDEPA or DEA) induced a significant increase in SCEs or an alteration of RI in vivo. At the highest in vitro concentration tested, alachlor induced a statistically-significant increase in MN, but no concomitant increase in CAs was seen. From analyses of our data and the literature on alachlor clastogenicity and exposure levels, we concluded that cytogenetic damage may not be an adequately sensitive marker for evaluating human exposure to alachlor. (C) 1999 Elsevier Science B.V. All rights reserved. C1 US EPA, Genet & Cellular Toxicol Branch, Div Environm Carcinogenesis, Res Triangle Pk, NC 27711 USA. NIEHS, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. RP Kligerman, AD (reprint author), US EPA, Genet & Cellular Toxicol Branch, Div Environm Carcinogenesis, Mail Drop 68, Res Triangle Pk, NC 27711 USA. NR 27 TC 7 Z9 7 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD APR 26 PY 1999 VL 441 IS 1 BP 95 EP 101 DI 10.1016/S1383-5718(99)00031-5 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 194WL UT WOS:000080217700010 PM 10224326 ER PT J AU Eglitis, MA Dawson, D Park, KW Mouradian, MM AF Eglitis, MA Dawson, D Park, KW Mouradian, MM TI Targeting of marrow-derived astrocytes to the ischemic brain SO NEUROREPORT LA English DT Article DE astrocyte; bone marrow; brain; fluorescent in situ hybridization; ischemia; transplantation ID CENTRAL-NERVOUS-SYSTEM; NONHEMATOPOIETIC TISSUES; STROMAL CELLS; BONE; TRANSPLANTATION; MICE; MICROGLIA; RAT AB BONE marrow progenitor cells have been shown to contribute to a small proportion of cells in nonhematopoietic tissues including the brain. In the acute unilateral middle cerebral artery occlusion model in spontaneously hypertensive rats following male-to-female bone marrow transplantation, we present data suggesting that 55% more marrow-derived cells, in general, and 161% more GFAP-positive astrocytes, in particular, migrate preferentially to the ischemic cortex than to the contralateral non-ischemic hemisphere. In addition to their biological significance, our findings could have therapeutic implications. Marrow-derived progenitor cells could potentially be used as vehicles for ex vivo gene transfer to the brain. C1 NINDS, Genet Pharmacol Unit, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Mouradian, MM (reprint author), NINDS, Genet Pharmacol Unit, Expt Therapeut Branch, NIH, Bldg 10,Room 5C116,10 Ctr Dr,MSC 1406, Bethesda, MD 20892 USA. OI Mouradian, M. Maral/0000-0002-9937-412X NR 17 TC 104 Z9 117 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD APR 26 PY 1999 VL 10 IS 6 BP 1289 EP 1292 DI 10.1097/00001756-199904260-00025 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 199NH UT WOS:000080488200026 PM 10363941 ER PT J AU Raedler, TJ Knable, MB Lafargue, T Urbina, RA Egan, MF Pickar, D Weinberger, DR AF Raedler, TJ Knable, MB Lafargue, T Urbina, RA Egan, MF Pickar, D Weinberger, DR TI In vivo determination of striatal dopamine D-2 receptor occupancy in patients treated with olanzapine SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE dopamine D-2 receptor; olanzapine; [I-123]IBZM SPECT; schizophrenia; antipsychotic ID PHOTON-EMISSION TOMOGRAPHY; ATYPICAL ANTIPSYCHOTIC OLANZAPINE; DOUBLE-BLIND; SCHIZOPHRENIC-PATIENTS; IN-VIVO; NEGATIVE SYMPTOMS; BASAL GANGLIA; HUMAN BRAIN; HALOPERIDOL; CLOZAPINE AB In vivo studies of dopamine D-2 receptor occupancy with atypical antipsychotics have suggested good clinical efficacy at occupancy rates less than those observed with typical neuroleptics, and few extrapyramidal side effects (EPS), possibly even at high levels of D-2 occupancy. We used [I-123]IBZM-SPECT to investigate striatal D-2 receptor occupancy in 10 schizophrenic patients who were treated with both a low (5 mg) and a high dose (20 mg) of the novel antipsychotic olanzapine without concomitant medications. The mean D-2 occupancy at 5 mg was 59.8% (range 33-81%); the mean D-2 occupancy at 20 mg was 82.8% (range 56-97%). Although the D-2 occupancy rates on 5 and 20 mg olanzapine were significantly different (P < 0.001), there were no significant differences in clinical ratings for psychiatric symptoms or extrapyramidal side effects between the two doses of olanzapine. These data suggest that: (1) olanzapine doses below those used routinely occupy D-2 receptors at levels approaching those associated with therapeutic response; (2) higher doses produce relatively high levels of D-2 occupancy rates; and (3) EPS are mild even at relatively high levels of D-2 occupancy. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NIMH, Expt Therapeut Branch, Bethesda, MD 20892 USA. RP Weinberger, DR (reprint author), NIMH, Clin Brain Disorders Branch, Bldg 10,Room 4S235, Bethesda, MD 20892 USA. NR 49 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 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD APR 26 PY 1999 VL 90 IS 2 BP 81 EP 90 DI 10.1016/S0925-4927(99)00010-4 PG 10 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 202AY UT WOS:000080631000001 PM 10482380 ER PT J AU Tanaka, H Ogasa, H Barnes, J Liang, CT AF Tanaka, H Ogasa, H Barnes, J Liang, CT TI Actions of bFGF on mitogenic activity and lineage expression in rat osteoprogenitor cells: effect of age SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE bFGF; IGF-I; PDGF; bone marrow osteoprogenitor cells; proliferation; gene expression ID FIBROBLAST GROWTH-FACTOR; COLLAGEN MESSENGER-RNA; BONE-FORMATION INVITRO; MARROW STROMAL CELLS; IGF-I; GENE-EXPRESSION; OLD RATS; DEVELOPMENTAL EXPRESSION; EXTRACELLULAR-MATRIX; ALKALINE-PHOSPHATASE AB Rat osteoprogenitor cells were used to examine the effects of bFGF on DNA synthesis and the expression of osteoblast (OB)-related genes, bFGF, as low as 0.1 ng/ml, stimulated DNA synthesis. bFGF also increased the mRNA level of osteopontin (OP) and decreased that of type I collagen (COL I). When cultures were grown in dexamethasone (DEX) to induce OB lineage commitment, the expression of COL I, alkaline phosphatase (AP) and OP was greatly enhanced. Subsequent incubation with bFGF partially negated the stimulatory effect of DEX on AP and COL I mRNAs. bFGF also inhibited the expression of osteocalcin mRNA in cells grown in 1,25(OH)(2)D-3 and DEX. Combined effects of bFGF with IGF-I or PDGF on DNA synthesis and OP expression were examined. bFGF + IGF-I, but not bFGF + PDGF, was more effective than PDGF alone. By comparing cells from adult and old animals, we found that bFGF-induced mitogenic activity was reduced significantly with age. In contrast, the effect of bFGF on the expression of OB genes was not significantly altered by age. These findings suggest that bFGF plays a dual role as a local positive and negative regulator on proliferation and osteogenic lineage expression, respectively, in osteoprogenitor cells, and that the mitogenic activity in response to bFGF was impaired in aging. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserved. C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Yamaguchi Univ, Sch Med, Dept Orthoped Surg, Yamaguchi 7558505, Japan. RP Liang, CT (reprint author), NIA, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 48 TC 34 Z9 40 U1 0 U2 0 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 APR 25 PY 1999 VL 150 IS 1-2 BP 1 EP 10 DI 10.1016/S0303-7207(99)00046-5 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 203ZR UT WOS:000080738900001 PM 10411294 ER PT J AU Wiegers, K Rutter, G Schubert, U Grattinger, M Krausslich, HG AF Wiegers, K Rutter, G Schubert, U Grattinger, M Krausslich, HG TI Cyclophilin A incorporation is not required for human immunodeficiency virus type 1 particle maturation and does not destabilize the mature capsid SO VIROLOGY LA English DT Article ID CYCLOSPORINE-A ANALOG; MAMMALIAN-CELLS; GAG POLYPROTEIN; HIV-1 PARTICLE; SDZ NIM-811; CORE DOMAIN; VPU PROTEIN; REPLICATION; INFECTIVITY; EXPRESSION AB The cellular protein cyclophilin A (CypA) is packaged into human immunodeficiency virus type 1 (HIV-1) virions through a specific interaction with the capsid (CA) domain of the Gag polyprotein. CypA is important for infectivity, but its role in viral replication is currently unknown. Previous reports suggested that CypA promotes uncoating or enhances maturation. We analyzed the morphology and capsid stability of HIV-1 variants defective in CypA binding and of virus grown in the presence of cyclosporin. Both cyclosporin treatment and alteration of Gly89 or Pro90 in the CypA-binding site of CA caused a 5- to 20-fold decrease in CypA incorporation. Virus produced from cyclosporin-treated cells and Variants G89V and G89A were 10- to 100-fold less infectious but exhibited normal virion morphologies with regular cone-shaped capsids. Irregular capsid morphologies and lower infectivities were observed for some other variants in the CypA-binding region. Decreased CypA incorporation did not reduce the kinetics of intracellular polyprotein processing or of virus release. No increase in immature particles was observed. These results suggest that CypA does not promote virion maturation. Furthermore, detergent stripping of virus particles with various CypA contents revealed no difference in capsid stability. Based on these results and those reported in the accompanying paper, it appears likely that CypA also is not an uncoating factor. Alternative models for CypA function are discussed, (C) 1999 Academic Press. C1 Univ Hamburg, Heinrich Pette Inst Expt Virol & Immunol, D-20251 Hamburg, Germany. NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RP Krausslich, HG (reprint author), Univ Hamburg, Heinrich Pette Inst Expt Virol & Immunol, Martinistr 52, D-20251 Hamburg, Germany. NR 51 TC 41 Z9 41 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD APR 25 PY 1999 VL 257 IS 1 BP 261 EP 274 DI 10.1006/viro.1999.9669 PG 14 WC Virology SC Virology GA 194GQ UT WOS:000080184200026 PM 10208939 ER PT J AU Ripley, TL Rocha, BA Oglesby, MW Stephens, DN AF Ripley, TL Rocha, BA Oglesby, MW Stephens, DN TI Increased sensitivity to cocaine, and over-responding during cocaine self-administration in tPA knockout mice SO BRAIN RESEARCH LA English DT Article DE cocaine; IV self-administration; tissue plasminogen activator; synaptic plasticity; prefrontal cortex; transgenic mice ID TISSUE-PLASMINOGEN-ACTIVATOR; MEDIAL PREFRONTAL CORTEX; LONG-TERM POTENTIATION; MESSENGER-RNA; GENE; SENSITIZATION; HIPPOCAMPUS; EXPRESSION; DEPRESSION; RECEPTORS AB Tissue plasminogen activator, tPA, is induced in the brain by electrical activity leading to synaptic remodeling. It is also induced in the prefrontal cortex (PFC) by acute cocaine. We investigated cocaine-induced locomotor activity, the development of sensitisation to cocaine and cocaine self-administration in mice lacking the gene encoding tPA. Mice lacking tPA (tPA knockout mice, tPA -/-) showed normal spontaneous activity, exhibited cocaine-induced locomotor activity at lower doses than wild-type (WT) control mice and showed a greater degree of cocaine-induced locomotor activity following repeated administration. tPA -/- and WT mice did not differ significantly in the time to acquire self-administration of cocaine (20 mu g/i.v. infusion) under an FR2 schedule. Following acquisition of this behavior, these groups also did not differ significantly in the rate of cocaine self-administration across the next three sessions. However, WT mice decreased responses on the active lever during signaled periods when reinforcer was not available; in contrast, tPA -/- mice did not. The emission of non-reinforced responses was most marked at the beginning of each 90 min daily session. This pattern of responding was not seen in tPA -/- mice pressing for food under an FR2 schedule of reinforcement. These results suggest that tPA may play a specific role either in retention of information between sessions or in behavioural inhibition in cocaine self-administration. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Sussex, Expt Psychol Lab, Brighton BN1 9QG, E Sussex, England. UNTHSC, Dept Pharmacol, Ft Worth, TX 76107 USA. NIDA, IRP, Intermural Program, Baltimore, MD 21224 USA. RP Stephens, DN (reprint author), Univ Sussex, Expt Psychol Lab, Brighton BN1 9QG, E Sussex, England. RI Stephens, David/G-2384-2012 NR 26 TC 22 Z9 22 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 APR 24 PY 1999 VL 826 IS 1 BP 117 EP 127 DI 10.1016/S0006-8993(99)01280-9 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 191VH UT WOS:000080041900013 PM 10216203 ER PT J AU Ahmad, F Cong, LN Wang, LM Holst, LS Landstrom, TR Quon, M Degerman, E Manganiello, VC AF Ahmad, F Cong, LN Wang, LM Holst, LS Landstrom, TR Quon, M Degerman, E Manganiello, VC TI Activation of phosphodiesterases 3B (PDE3B) and PDE4 in FDCP2 cells: Roles of protein kinase B and MAP kinase SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, NHLBI, NIH, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1511 EP A1511 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033401091 ER PT J AU Akbar, M Kim, HY AF Akbar, M Kim, HY TI A role for docosahexanoic acid in neuronal apoptosis SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA, Sect Mass Spectrometry, LMBB, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1435 EP A1435 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400652 ER PT J AU Aymerich, MS Alberdi, E Becerra, SP AF Aymerich, MS Alberdi, E Becerra, SP TI Binding of the neurotrophic factor pigment epithelium derived factor (PEDF) to the bovine retina SO FASEB JOURNAL LA English DT Meeting Abstract C1 NEI, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1575 EP A1575 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033401456 ER PT J AU Barrett, WC DeGnore, J Keng, YF Zhang, ZY Yim, MB Chock, PB AF Barrett, WC DeGnore, J Keng, YF Zhang, ZY Yim, MB Chock, PB TI Roles of free radicals in signal transduction mediated by reversible tyrosine phosphorylation. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Bronx, NY 10461 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1487 EP A1487 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400950 ER PT J AU Basanez, G Nechushtan, A Drozhinin, O Tutt, S Wood, KA Hsu, YT Youle, RJ Zimmerberg, J AF Basanez, G Nechushtan, A Drozhinin, O Tutt, S Wood, KA Hsu, YT Youle, RJ Zimmerberg, J TI Studying the mechanism of Bax induced membrane destabilization: Does Bax promote lipidic pore formation? SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHD, LCMB, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1436 EP A1436 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400657 ER PT J AU Basu, N Ciotti, M Hsai, N Owens, IS AF Basu, N Ciotti, M Hsai, N Owens, IS TI Detoxification of natural chemicals by a subset of the human family A UDP-glucuronosyltransferase isozymes 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1442 EP A1442 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400693 ER PT J AU Baumann, CT Reyes, JC Lim, CS Hager, GL AF Baumann, CT Reyes, JC Lim, CS Hager, GL TI PML localizes with GRIP-1 and functions in glucocorticoid receptor-dependent transcription SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Natl Inst Hlth, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1374 EP A1374 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400311 ER PT J AU Bevan, DR Li, L Pedersen, LG Darden, TA AF Bevan, DR Li, L Pedersen, LG Darden, TA TI Molecular dynamics of d(CCAACGTTGG)(2) in the crystal and in solution. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Virginia Tech, Dept Biochem, Blacksburg, VA 24061 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 NR 0 TC 0 Z9 0 U1 0 U2 3 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1584 EP A1584 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033401509 ER PT J AU Bortner, CD Cidlowski, JA AF Bortner, CD Cidlowski, JA TI Caspase independent/dependent regulation of K+ efflux, cell shrinkage, and mitochondrial membrane potential during lymphocyte apoptosis SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1341 EP A1341 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400119 ER PT J AU Busby, SA Philipsberg, GA Shao, L Shaw, P Sakaguchi, K Appella, E Haltiwanger, RS AF Busby, SA Philipsberg, GA Shao, L Shaw, P Sakaguchi, K Appella, E Haltiwanger, RS TI Acetylation of the C-terminal negative regulatory domain of p53 in human colon cancer cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 SUNY Stony Brook, Stony Brook, NY 11794 USA. Inst Pathol, Lausanne, Switzerland. NCI, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1539 EP A1539 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033401250 ER PT J AU Casas-Finet, JR Urbaneja, MA Wu, M Karpel, RL Ozarowski, A Maki, AH AF Casas-Finet, JR Urbaneja, MA Wu, M Karpel, RL Ozarowski, A Maki, AH TI A spectroscopic study of the double-stranded (DS) nucleic acid binding, destabilizing, and strand transfer properties of HIV-1 nucleocapsid (NC) protein p7 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, AIDS Vaccine Program, SAIC, Frederick, MD 21702 USA. Univ Calif Davis, Davis, CA 95616 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1501 EP A1501 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033401035 ER PT J AU Chao, CC Stadtman, ER AF Chao, CC Stadtman, ER TI Effects of H2O2 on caspase 3 activity is dependent upon treatment using direct addition of H2O2 or a generating system. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Biochem 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1434 EP A1434 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400645 ER PT J AU Chen, J Simons, SS AF Chen, J Simons, SS TI Structure-function relationships among the novel proteins, GMEB-1 and-2, binding to the glucocorticoid modulatory element (GME). SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, Steroid Hormones Sect, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1464 EP A1464 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400815 ER PT J AU Chevion, M Berlett, BS Stadtman, ER AF Chevion, M Berlett, BS Stadtman, ER TI Ternary complexes containing iron and amino acids. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Biochem 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1397 EP A1397 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400441 ER PT J AU Copeland, TD Guszczynski, T AF Copeland, TD Guszczynski, T TI A capillary electrophoresis study of Zn(II) binding to the cysteine rich domain of RAF-1. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1478 EP A1478 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400901 ER PT J AU Davis, DA Yarchoan, DR AF Davis, DA Yarchoan, DR TI Redox regulation of the dimeric retroviral proteases: A structural comparison SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, HIV & AIDS Malignancy 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1365 EP A1365 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400257 ER PT J AU Evans-Storms, RB Cidlowski, JA AF Evans-Storms, RB Cidlowski, JA TI Glucocorticoids suppress apoptosis induced by serum starvation of rat hepatoma SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1343 EP A1343 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400130 ER PT J AU Ferrari, D Hur, O Woehl, E Miles, E Banik, U Dunn, M AF Ferrari, D Hur, O Woehl, E Miles, E Banik, U Dunn, M TI Role of an inter-subunit salt bridge in the regulation of substrate channeling in tryptophan synthase SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Univ Calif Riverside, Dept Biochem, Riverside, CA 92521 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1349 EP A1349 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400166 ER PT J AU Fiskum, G Kowaltowski, AJ Smaill, SS Russell, JT AF Fiskum, G Kowaltowski, AJ Smaill, SS Russell, JT TI Bcl-2, cyclosporin A and BAPTA-AM increase the normal mitochondrial membrane potential in PC12 cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Maryland, Baltimore, MD 21201 USA. Univ Estadual Campinas, BR-13081970 Campinas, SP, Brazil. NIH, Bethesda, MD 20892 USA. RI Kowaltowski, Alicia/H-8698-2012 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1589 EP A1589 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033401533 ER PT J AU Fletcher, TM Ryu, BW Baumann, CT Warren, BS Hager, GL AF Fletcher, TM Ryu, BW Baumann, CT Warren, BS Hager, GL TI Remodeling of reconstituted MMTV chromatin in vitro by purified glucocorticoid receptor SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Lab Receptor Biol & Gene Express, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1470 EP A1470 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400852 ER PT J AU Gladyshev, VN Sun, QA Wu, YL Zappacosta, F Jeang, KT Lee, BJ Hatfield, DL AF Gladyshev, VN Sun, QA Wu, YL Zappacosta, F Jeang, KT Lee, BJ Hatfield, DL TI Redox regulation of cell signaling by selenocysteine in mammalian thioredoxin reductases SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Nebraska, Lincoln, NE 68588 USA. NIAID, NIH, Bethesda, MD 20892 USA. Seoul Natl Univ, Seoul 151, South Korea. NCI, NIH, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008; Gladyshev, Vadim/A-9894-2013 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1579 EP A1579 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033401483 ER PT J AU Gonzalez, M Weiler, S Ferretti, JA Ginsburg, A AF Gonzalez, M Weiler, S Ferretti, JA Ginsburg, A TI Reversible, thermal unfolding of a vnd/NK-2 (ventral nervous system defective) homeodomain mutant protein. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1386 EP A1386 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400381 ER PT J AU Hardwick, JP Peters, J Malmer, M Gonzalez, FJ AF Hardwick, JP Peters, J Malmer, M Gonzalez, FJ TI Regulation of the CYP4F1 Leukotriene B-4 Omega hydroxylase gone during peroxisomal proliferator induced hepatocarcinogenesis in PPAR (+/+) and the PPAR (-/-) knockout mouse. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NE Ohio Univ, Coll Med, Rootstown, OH 44272 USA. NCI, Lab Metab, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1401 EP A1401 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400461 ER PT J AU Hardwick, JP Zhang, XL Malmer, M Donaldson, E Chen, LP AF Hardwick, JP Zhang, XL Malmer, M Donaldson, E Chen, LP TI Human tissue and tumor localized expression of the CYP4F2 hepatic Leukotriene B-4 Omega hydroxylase P450 Gene. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NE Ohio Univ, Coll Med, Rootstown, OH 44272 USA. NIDDK, Lab Mol Recognit, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1344 EP A1344 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400133 ER PT J AU Harvey, JJ Lee, PS Fucs, SF Knutson, JR Han, MK AF Harvey, JJ Lee, PS Fucs, SF Knutson, JR Han, MK TI Use of time resolved fluorescence spectroscopy to investigate the binding of mutant HIV-1 integrase to a synthetic oligonucleotide substrate SO FASEB JOURNAL LA English DT Meeting Abstract C1 Georgetown Univ, Med Ctr, NIH, Washington, DC 20057 USA. Penn State Univ, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1571 EP A1571 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033401433 ER PT J AU Hoffmann, C Pradel, G Heine, P Jacobson, KA Zimmermann, H AF Hoffmann, C Pradel, G Heine, P Jacobson, KA Zimmermann, H TI Inhibition of ecto-ATPase and ecto-apyrase by pyridoxal phosphate-related compounds. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, MOl Recognit Sect, LBC, NIH, Bethesda, MD 20892 USA. Univ Frankfurt, Inst Zool, Biozentrum, D-60439 Frankfurt, Germany. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 1 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1350 EP A1350 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400168 ER PT J AU Hoque, ATMS Liu, XB Kagami, H Swaim, WD Wellner, RB O'Connell, BC Ambudkar, IS Baum, BJ AF Hoque, ATMS Liu, XB Kagami, H Swaim, WD Wellner, RB O'Connell, BC Ambudkar, IS Baum, BJ TI Construction and function of a recombinant adenovirus encoding an human aquaporin 1-green fluorescence protein fusion product SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDCR, GTTB, NIH, Bethesda, MD 20892 USA. NIDCR, CIC, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1544 EP A1544 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033401276 ER PT J AU Hou, XH Foly, S Robinson, MA AF Hou, XH Foly, S Robinson, MA TI Isolation of intracellular factors that interact with HTLV-1 pX region encoded protein p13 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Immunogenet Lab, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1502 EP A1502 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033401037 ER PT J AU Huizing, M Anikster, Y Gahl, WA AF Huizing, M Anikster, Y Gahl, WA TI Intracellular localization and membrane orientation of the HPS-1 protein. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHD, Heritable Disorders Branch, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1568 EP A1568 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033401419 ER PT J AU Hutter, D Liu, Y AF Hutter, D Liu, Y TI Structure-function studies on MAP kinase phosphatase-1 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA, Gerontol Res Ctr, Biol Chem Lab, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1488 EP A1488 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400956 ER PT J AU Kakuta, Y Sueyoshi, T Pedersen, LC Negishi, K AF Kakuta, Y Sueyoshi, T Pedersen, LC Negishi, K TI Crystal structure of human heparan sulfate N-sulfotransferase: the conserved PAPS-binding site and reaction mechanism. SO FASEB JOURNAL LA English DT Meeting Abstract C1 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1364 EP A1364 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400253 ER PT J AU Karp, BI Ali, S Takenaka, T Brady, RO Medin, JA AF Karp, BI Ali, S Takenaka, T Brady, RO Medin, JA TI Modification of the human alpha GalactosidaseA (alpha GalA) C-terminus enhances uptake by Fabry patient fibroblast SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1403 EP A1403 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400475 ER PT J AU Kenan, Y Shakur, Y Murata, T Manganiello, VC AF Kenan, Y Shakur, Y Murata, T Manganiello, VC TI Function of the N-terminal region in cyclic nucleotide phosphodiesterase 3 (PDE 3). SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, PCCMB, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1421 EP A1421 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400578 ER PT J AU Krasnickas, EA Baumann, CT Smith, CL Hager, GL AF Krasnickas, EA Baumann, CT Smith, CL Hager, GL TI Glucocorticoid receptor mutants indicate differential requirements for the transcriptional activation of transient and stably replicating MMTV templates SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Lab Receptor Biol & Gene Express, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1470 EP A1470 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400851 ER PT J AU Lacourciere, GM Stadtman, TC AF Lacourciere, GM Stadtman, TC TI The role of selenocysteine in Haemophilus influenzae selenophosphate synthetase. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Biochem 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1355 EP A1355 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400198 ER PT J AU Li, J Huang, FL Huang, KP AF Li, J Huang, FL Huang, KP TI Glutathiolation of rat brain neurogranin by glutathione sulfoxide derived from S-nitrosoglutathione. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD 20854 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1420 EP A1420 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400569 ER PT J AU Lin, B Hiraiwa, H Pan, CJ Chou, JY AF Lin, B Hiraiwa, H Pan, CJ Chou, JY TI Inactivation of the glucose-8-phosphate transporter causes glycogen storage disease type 1b SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHHD, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1375 EP A1375 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400318 ER PT J AU Ma, JX Clark, J Myers, P Lindzey, J Korach, K Zeldin, D AF Ma, JX Clark, J Myers, P Lindzey, J Korach, K Zeldin, D TI Mouse CYP2J5 expression is regulated by sex hormones SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1347 EP A1347 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400152 ER PT J AU Malek, NN Hager, GL Smith, CL AF Malek, NN Hager, GL Smith, CL TI Glucocorticoid receptor and cAMP pathway cross-talk regulates MMTV promoter activity in a chromatin dependent manner SO FASEB JOURNAL LA English DT Meeting Abstract C1 George Washington Univ, NIH, Washington, DC 20052 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1371 EP A1371 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400292 ER PT J AU Mandal, AK Zhang, Z Mukherjee, AB AF Mandal, AK Zhang, Z Mukherjee, AB TI Murine pancreatic soluble phospholipase A2: Possible modifier role in gastrointestinal cancers 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1550 EP A1550 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033401312 ER PT J AU Moskovitz, J Poston, JM Berlett, BS Levine, RL Stadtman, ER AF Moskovitz, J Poston, JM Berlett, BS Levine, RL Stadtman, ER TI Characterization of substrate stereospecificity of the peptide-methionine sulfoxide reductase (MsrA). SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1354 EP A1354 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400192 ER PT J AU Moustafa, ME Carlson, BA Lee, BJ El-Saadani, MA Kandeel, KM Feigenbaum, L Diamond, AM Hatfield, DL AF Moustafa, ME Carlson, BA Lee, BJ El-Saadani, MA Kandeel, KM Feigenbaum, L Diamond, AM Hatfield, DL TI Overexpression of selenocysteine (Sec) tRNA in transgenic mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, BRL, NIH, Bethesda, MD 20892 USA. Seoul Natl Univ, LMG, IMBG, Seoul 151742, South Korea. AU, FS, DB, Alexandria, Egypt. FCRDC, SAIC, Frederick, MD 21702 USA. UIC, DHND, Chicago, IL 60612 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1506 EP A1506 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033401064 ER PT J AU Nam, SW Clair, T Campo, C Liotta, LA Stracke, ML AF Nam, SW Clair, T Campo, C Liotta, LA Stracke, ML TI Overexpression of autotaxin (ATX) augments tumorigenic potential in NIH-3T3 fibroblasts SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Pathol 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1421 EP A1421 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400576 ER PT J AU Newcomb, FM Davis, DA Moskovitz, J Levine, RL Yarchoan, R AF Newcomb, FM Davis, DA Moskovitz, J Levine, RL Yarchoan, R TI Inactivation of HIV-1 and HIV-2 proteases by hydrogen peroxide SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1502 EP A1502 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033401038 ER PT J AU Ni, Y McPhie, P Coleman, WG AF Ni, Y McPhie, P Coleman, WG TI NADP(+) is the natural cofactor of ADP-L-glycero-D-mannoheptase 6-epimerase SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, Lab Biochem & Genet, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1367 EP A1367 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400270 ER PT J AU Pal, D Pande, S Wheeler, D Hinton, D AF Pal, D Pande, S Wheeler, D Hinton, D TI Deletion analysis of the bacteriophage T4 AsiA protein, a co-activator of T4 middle transcription. 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1462 EP A1462 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400804 ER PT J AU Rebois, RV VanRyk, D Schuck, P AF Rebois, RV VanRyk, D Schuck, P TI Determining the K-D for heterotrimeric G protein subunits by surface plasmon resonance spectroscopy. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, LMCN, Membrane Biochem Sect, Bethesda, MD 20892 USA. NIH, BEPS, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1510 EP A1510 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033401087 ER PT J AU Rhee, S Martin, RG Rosner, JL Davies, DR AF Rhee, S Martin, RG Rosner, JL Davies, DR TI A novel DNA-binding motif of MarA: the first structure for an AraC family transcriptional activator SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, Mol Biol 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1392 EP A1392 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400414 ER PT J AU Ro, HS Miles, EW AF Ro, HS Miles, EW TI Catalytic mechanism of tryptophan synthase from ph studies. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1355 EP A1355 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400197 ER PT J AU Rodriguez, P Patton, WA Adamik, R Yoo, HS Zang, GF Moss, J Vaughan, M AF Rodriguez, P Patton, WA Adamik, R Yoo, HS Zang, GF Moss, J Vaughan, M TI Structural elements of ADP-ribosylation factor 1 (ARF1) required for functional interaction with cytohesin-1. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, PCCMB, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1366 EP A1366 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400263 ER PT J AU Rogers, K Ye, L Han, CL Watanabe, H Liau, G AF Rogers, K Ye, L Han, CL Watanabe, H Liau, G TI Characterization of the hyaluronan binding protein TSG-6 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Amer Red Cross, Holland Lab, Rockville, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1495 EP A1495 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033401001 ER PT J AU Schroeder, BG Barry, CE AF Schroeder, BG Barry, CE TI Molecular genetic analysis of a family of M-tuberculosis mycolic acid methyltransferases SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, TB Res Sect, NIH, Bethesda, MD 20892 USA. RI Barry, III, Clifton/H-3839-2012 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1380 EP A1380 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400343 ER PT J AU Scoltock, AB Bird, GSJ Putney, J Cidlowski, JA AF Scoltock, AB Bird, GSJ Putney, J Cidlowski, JA TI The role of calcium signaling in anti-fas antibody induced apoptosis of Jurkat cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1434 EP A1434 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400643 ER PT J AU Selengut, J Levine, R AF Selengut, J Levine, R TI MDP-1: A member of a new class of tyrosine phosphatase. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1487 EP A1487 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400953 ER PT J AU Shakur, Y Takeda, K Ferrans, VJ Manganiello, VC AF Shakur, Y Takeda, K Ferrans, VJ Manganiello, VC TI Mapping the N-terminal membrane-association domains of mouse PDE3B SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, PCCMB, NIH, Bethesda, MD 20892 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. Otsuka Amer Pharmaceut Inc, Rockville, MD 20850 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1421 EP A1421 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400579 ER PT J AU Song, Y Basrur, V Sakaguchi, K Turpin, JA Imman, JK Rice, WG Appella, E AF Song, Y Basrur, V Sakaguchi, K Turpin, JA Imman, JK Rice, WG Appella, E TI Syntheses and mechanism study of novel pyridinioalkanoyl thiolesters (PATEs) as anti-HTV-1 agents that target the viral nucleocapsid protein zinc fingers SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, LCB, NIH, Bethesda, MD 20892 USA. So Res Inst, Birmingham, AL 35255 USA. NIAID, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1352 EP A1352 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400182 ER PT J AU Souza-Pinto, NC Hudson, EK Croteau, DL Bohr, VA Hansford, RG AF Souza-Pinto, NC Hudson, EK Croteau, DL Bohr, VA Hansford, RG TI Age-associated changes in DNA damage and repair in rat mitochondria SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA, Gerontol Res Ctr, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. RI Souza-Pinto, Nadja/C-3462-2013 OI Souza-Pinto, Nadja/0000-0003-4206-964X 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1454 EP A1454 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400760 ER PT J AU Stetler-Stevenson, WG AF Stetler-Stevenson, WG TI Extracellular matrix proteolysis: New roles and novel targets in human disease SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Extracellular Matrix Pathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1588 EP A1588 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033401526 ER PT J AU Stone, AL Longas, MO AF Stone, AL Longas, MO TI Sulfated oligoxylans isolated by combinatorial approach vs target heparin-mimetic functions: Characterization by FTIR spectroscopy SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD 20892 USA. Purdue Univ, Hammond, IN 46323 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1385 EP A1385 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400376 ER PT J AU Sueyoshi, T Kawamoto, T Zelko, I Negishi, M AF Sueyoshi, T Kawamoto, T Zelko, I Negishi, M TI Phenobarbital-responsive enhancer module (PBREM) of human CYP2B6 gene and inducible transactivation by nuclear receptor CAR. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, RTP, NIH, Res Triangle Pk, NC 27709 USA. RI Zelko, Igor/L-2673-2013; Kawamoto, Takeshi/D-7938-2015 OI Zelko, Igor/0000-0003-3976-3884; Kawamoto, Takeshi/0000-0003-3337-1775 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1373 EP A1373 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400305 ER PT J AU Szczepanowski, RH Ruvinov, SB Nosworthy, NJ Sondej, M Peterkofsky, A Ginsburg, A AF Szczepanowski, RH Ruvinov, SB Nosworthy, NJ Sondej, M Peterkofsky, A Ginsburg, A TI Phosphorylation destabilizes the amino terminal domain of enzyme I of the E-coli pep : sugar phosphotransferase system (PTS). SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1569 EP A1569 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033401423 ER PT J AU Trawick, ML Bowser, TE Folk, JE AF Trawick, ML Bowser, TE Folk, JE TI Inhibition of gamma-glutamylamine cyclotransferase SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDR, OPCB, NIH, Bethesda, MD 20892 USA. Baylor Univ, Dept Chem & Biochem, Waco, TX 76798 USA. Baylor Univ, BMS, Waco, TX 76798 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1350 EP A1350 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400172 ER PT J AU Tsao, CC Zeldin, DC Luo, G Ma, J Goldstein, JA AF Tsao, CC Zeldin, DC Luo, G Ma, J Goldstein, JA TI Extrahepatic distribution of murine CYP2CS and stereoselectivity of arachidonic acid metabolism SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Res Triangle Pk, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1346 EP A1346 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400144 ER PT J AU Tully, DB Collins, BJ Smith, CS Mumtaz, MM Chapin, RE AF Tully, DB Collins, BJ Smith, CS Mumtaz, MM Chapin, RE TI New biomarkers of toxicity for four high priority heavy metal pollutants. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1407 EP A1407 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400496 ER PT J AU Vann, LR Milstien, S AF Vann, LR Milstien, S TI Regulation of inducible nitric oxide synthase and GTP cyclohydrolase 1 gene expression by sphingolipid metabolites SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH, Lab Cellular & 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1420 EP A1420 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400572 ER PT J AU Venkatachalam, KV Fuda, H Strott, CA AF Venkatachalam, KV Fuda, H Strott, CA TI Identification and characterization of ATP-binding site in the ATP sulfurylase domain of bifunctional human PAPS synthase. 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1365 EP A1365 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400255 ER PT J AU Walz, FG Kumar, K Arni, RK Kreitman, RJ AF Walz, FG Kumar, K Arni, RK Kreitman, RJ TI 3-D structure of ribonuclease T-1 complexed with a phosphonate analog of GpU. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Kent State Univ, Kent, OH 44242 USA. UNESP, IBILCE, S J Do Rio Preto, SP, Brazil. NCI, Bethesda, MD 20892 USA. RI Arni, Raghuvir/B-2222-2013 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1356 EP A1356 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400203 ER PT J AU Wang, LH Kirken, RA Erwin, RA Farrar, WL AF Wang, LH Kirken, RA Erwin, RA Farrar, WL TI Regulation of T helper cell activity by tyrphostin AG-490 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Cytokine Mol Mechanisms Sect, Mol Immunoregulat Lab, NIH, Frederick, MD 21702 USA. NCI, IRSP, SAIC Frederick, FCRDC, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1558 EP A1558 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033401357 ER PT J AU Wolff, EC Lee, YB Joe, YA Dimitriadis, EK Park, MH AF Wolff, EC Lee, YB Joe, YA Dimitriadis, EK Park, MH TI Complex formation between deoxyhypusine synthase and its protein substrate, the eIF5A precursor SO FASEB JOURNAL LA English DT Meeting Abstract C1 Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA. NIH, Bioengn & Phys Sci Program, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1527 EP A1527 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033401178 ER PT J AU Xiang, Y Moss, B AF Xiang, Y Moss, B TI Identification of human and mouse homologs of a family of secreted viral glycoproteins implicated as immune modulators SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Viral Dis 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1502 EP A1502 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033401039 ER PT J AU Xie, D Gulnik, S Yu, B Gustchina, E Nathan, A Sowder, RC Rosenberg, S Erickson, JW AF Xie, D Gulnik, S Yu, B Gustchina, E Nathan, A Sowder, RC Rosenberg, S Erickson, JW TI The urokinase-binding site of urokinase receptor represents an independent folding unit and involves structures from both domain I and domain (II+III) SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Struct Biochem Program, Frederick, MD USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, AIDS Vaccine Program, Frederick, MD USA. Chiron Corp, Emeryville, CA 94608 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1485 EP A1485 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400940 ER PT J AU Yang, XY Wang, LH Kirken, RA Erwin, RA Farrar, WL AF Yang, XY Wang, LH Kirken, RA Erwin, RA Farrar, WL TI MAPK signaling pathway involved in inhibition of AG-490 on T cell proliferation SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC, IRSP, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1389 EP A1389 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400395 ER PT J AU Zhang, WY Skarlatos, SI Chao, FF Kruth, HS AF Zhang, WY Skarlatos, SI Chao, FF Kruth, HS TI Apolipoprotein B stimulates formation of monocyte-macrophage surface-connected compartments and mediates uptake of LDL-derived liposomes into these compartments. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Sect Expt Atherosclerosis, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1475 EP A1475 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400883 ER PT J AU Zhang, X Chen, L Hardwick, JP AF Zhang, X Chen, L Hardwick, JP TI Proximal promoter structure and transcriptional regulation of the CYP4F2 human liver leukotriene B-4 omega-hydroxylase gene. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NE Ohio Univ, Coll Med, Rootstown, OH 44272 USA. NIDDK, Lab Mol Recognit, 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1462 EP A1462 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400806 ER PT J AU Ohno, H Tomemori, T Nakatsu, F Okazaki, Y Aguilar, RC Foelsch, H Mellman, I Saito, T Shirasawa, T Bonifacino, JS AF Ohno, H Tomemori, T Nakatsu, F Okazaki, Y Aguilar, RC Foelsch, H Mellman, I Saito, T Shirasawa, T Bonifacino, JS TI mu 1B, a novel adaptor medium chain expressed in polarized epithelial cells SO FEBS LETTERS LA English DT Article ID DARBY CANINE KIDNEY; CLATHRIN-ASSOCIATED PROTEINS; SORTING SIGNALS; MDCK CELLS; INTERNALIZATION SIGNALS; STRUCTURAL REQUIREMENTS; TYROSINE; ENDOCYTOSIS; RECEPTOR; DISTINCT AB The apical and basolateral plasma membrane domains of polarized epithelial cells contain distinct sets of integral membrane proteins. Biosynthetic targeting of proteins to the basolateral plasma membrane is mediated by cytosolic tail determinants, many of which resemble signals involved in the rapid endocytosis or lysosomal targeting, Since these signals are recognized by adaptor proteins, we hypothesized that there could be epithelial-specific adaptors involved in polarized sorting. Here, we report the identification of a novel member of the adaptor medium chain family, named mu 1B, which is closely related to the previously described mu 1A (79% amino acid sequence identity). Northern blotting and in situ hybridization analyses reveal the specific expression of mu 1B mRNA in a subset of polarized epithelial and exocrine cells. Yeast two-hybrid analyses show that mu 1B is capable of interacting with generic tyrosine-based sorting signals. These observations suggest that mu 1B may be involved in protein sorting events specific to polarized cells. (C) 1999 Federation of European Biochemical Societies. C1 Chiba Univ, Grad Sch Med, Dept Mol Genet, Chuo Ku, Chiba 2608670, Japan. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Tokyo Metropolitan Inst Gerontol, Dept Mol Genet, Itabashi Ku, Tokyo 1730015, Japan. Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06520 USA. RP Ohno, H (reprint author), Chiba Univ, Grad Sch Med, Dept Mol Genet, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan. RI Saito, Takashi/C-9684-2009; Ohno, Hiroshi/L-7899-2014 OI Saito, Takashi/0000-0001-9495-3547; Ohno, Hiroshi/0000-0001-8776-9661 NR 42 TC 179 Z9 184 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD APR 23 PY 1999 VL 449 IS 2-3 BP 215 EP 220 DI 10.1016/S0014-5793(99)00432-9 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 192LW UT WOS:000080081200025 PM 10338135 ER PT J AU Chan, PP Lin, M Faruqi, AF Powell, J Seidman, MM Glazer, PM AF Chan, PP Lin, M Faruqi, AF Powell, J Seidman, MM Glazer, PM TI Targeted correction of an episomal gene in mammalian cells by a short DNA fragment tethered to a triplex-forming oligonucleotide SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DOUBLE-HELICAL DNA; HOMOLOGOUS RECOMBINATION; PSORALEN PHOTOADDUCTS; GENOMIC DNA; MUTAGENESIS; CLEAVAGE; REPAIR; SITE; EXPRESSION; NUCLEASE AB Tripler-forming oligonucleotides (TFOs) can bind to polypurine/polypyrimidine regions in DNA in a sequence-specific manner and provoke DNA repair. We have coupled a TFO to a short donor fragment of DNA that shares homology to a selected gene as a strategy to mediate gene targeting and correction. In this bifunctional oligonucleotide, the TFO domain is designed to bind the target gene and stimulate repair and recombination, with the donor domain positioned for recombination and information transfer. A series of these tethered donor-TFO (TD-TFO) molecules with donor domains of 40-44 nucleotides and TFO domains in both the purine and pyrimidine tripler motifs were tested for their ability to mediate either gene correction or mutation of a supF reporter gene contained in a SV40 shuttle vector in mammalian cells. In vitro binding assays revealed that the attachment of the donor domain via a flexible linker did not significantly alter the binding affinity of the TFO domain for the polypurine site in the supF target DNA, with equilibrium dissociation constants in the 10(-8) M range. Experiments in which the target vector and the linked TD-TFOs were pre-incubated in vitro and co-transfected into cells led to conversion frequencies approaching 1%, 4-fold greater than with the two domains unlinked, When cells that had been previously transfected with the SV40 vector were electroporated with the TD-TFOs, frequencies of base pair-specific gene correction were seen in the range of 0.04%, up to 50-fold over background and at least 3-fold over either domain alone or in unlinked combinations. Sequence conversion by the TD-TFOs was achieved using either single- or double-stranded donor domains and either tripler motif, Substitution of either domain in the TD-TFO with control sequences yielded reagents with diminished activity, as did mixtures of unlinked TFO and donor DNA segments, The boost in activity provided by the attached TFO domain was reduced in cells deficient in the nucleotide excision repair factor XPA but was restored in a subclone of these cells expressing XPA cDNA, suggesting a role for nucleotide excision repair in the pathway of triple helix-stimulated gene conversion. The ability to correct or mutate a specific target site in mammalian cells using the TD-TFO strategy may provide a useful tool for research and possibly for therapeutic applications. C1 Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. NIA, NIH, Baltimore, MD 21224 USA. RP Glazer, PM (reprint author), Yale Univ, Sch Med, Dept Therapeut Radiol, POB 206040, New Haven, CT 06520 USA. FU NIGMS NIH HHS [GM07205, GM54731] NR 27 TC 100 Z9 102 U1 0 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 APR 23 PY 1999 VL 274 IS 17 BP 11541 EP 11548 DI 10.1074/jbc.274.17.11541 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 188EX UT WOS:000079834800016 PM 10206960 ER PT J AU Jian, XY Sainz, E Clark, WA Jensen, RT Battey, JF Northup, JK AF Jian, XY Sainz, E Clark, WA Jensen, RT Battey, JF Northup, JK TI The bombesin receptor subtypes have distinct G protein specificities SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHOLIPASE-C ISOZYMES; NEUROMEDIN-B RECEPTOR; HUMAN ORPHAN RECEPTOR; BETA-GAMMA-SUBUNITS; PEPTIDE RECEPTOR; ALPHA-SUBUNITS; HIGH-AFFINITY; GUANINE-NUCLEOTIDES; SF9 CELLS; KINASE-C AB We used an in situ reconstitution assay to examine the receptor coupling to purified G protein alpha subunits by the bombesin receptor family, including gastrin-releasing peptide receptor (GRP-R), neuromedin B receptor (NMB-R), and bombesin receptor subtype 3 (BRS-3), Cells expressing GRP-R or NMB-R catalyzed the activation of squid retinal G alpha(q) and mouse G alpha(q) but not bovine retinal G alpha(t) or bovine brain G alpha(i/o). The GRP-R- and NMB-R-catalyzed activations of Ga, Were dependent upon and enhanced by different py dimers in the same rank order as follows: bovine brain beta gamma > beta(1)gamma(2) >> beta(1)gamma(1). Despite these qualitative similarities, GRP-R and NMB-R had distinct kinetic properties in receptor-G protein coupling. GRP-R had higher affinities for bovine brain beta gamma, beta(1)gamma(1), and beta(1)gamma(2) and squid retinal G alpha(q). In addition, GRP-R showed higher catalytic activity on squid G alpha(q). Like GRP-R and NMB-R, BRS-3 did not catalyze GTP gamma S binding to G alpha(i/o) or G alpha. However, BRS-3 showed little, if any, coupling with squid G alpha(q) but clearly activated mouse G alpha(q). GRP-R and NMB-R catalyzed GTP gamma S binding to squid and mouse G alpha(q), with GRP-R activating squid G alpha(q) more effectively, and NMB-R also showed slight preference for squid G alpha(q). These studies reveal that the structurally similar bombesin receptor subtypes, in particular BRS-3, possess distinct coupling preferences among members of the G alpha(q) family. C1 Natl Inst Deafness & Other Commun Disorders, Lab Cellular Biol, Rockville, MD 20850 USA. Natl Inst Deafness & Other Commun Disorders, Mol Biol Lab, Rockville, MD 20850 USA. NIDDKD, Digest Dis Sect, NIH, Bethesda, MD 20892 USA. RP Northup, JK (reprint author), Natl Inst Deafness & Other Commun Disorders, Lab Cellular Biol, 5 Res Ct, Rockville, MD 20850 USA. NR 37 TC 54 Z9 55 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 APR 23 PY 1999 VL 274 IS 17 BP 11573 EP 11581 DI 10.1074/jbc.274.17.11573 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 188EX UT WOS:000079834800020 PM 10206964 ER PT J AU Rudolph, AE Stuckey, JA Zhao, Y Matthews, HR Patton, WA Moss, J Dixon, JE AF Rudolph, AE Stuckey, JA Zhao, Y Matthews, HR Patton, WA Moss, J Dixon, JE TI Expression, characterization, and mutagenesis of the Yersinia pestis murine toxin, a phospholipase D superfamily member SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; D DEFINES; PHOSPHATASE; PHOSPHATIDYLCHOLINE; FAMILY; GENE; PHOSPHOHISTIDINE; IDENTIFICATION; INTERMEDIATE; PURIFICATION AB A phospholipase D (PLD) superfamily was recently identified that contains proteins of highly diverse functions with the conserved motif HXKX(4)DX(6)G(G/S). The superfamily includes a bacterial nuclease, human and plant PLD enzymes, cardiolipin synthases, phosphatidylserine synthases, and the murine toxin from Yersinia pestis (Ymt), Ymt is particularly effective as a prototype for family members containing two conserved motifs, because it is smaller than many other two-domain superfamily enzymes, and it can be overexpressed, Large quantities of pure recombinant Ymt allowed the formation of diffraction-quality crystals for x-ray structure determination, Dimeric Ymt was shown to have PLD-like activity as demonstrated by the hydrolysis of phosphatidylcholine. Ymt also used bis(para-nitrophenol) phosphate as a substrate. Using these substrates, the amino acids essential for Ymt function were determined. Specifically, substitution of histidine or lysine in the conserved motifs reduced the turnover rate of bis(para-nitrophenol) phosphate by a factor of 10(4) and phospholipid turnover to an undetectable level. The role of the conserved residues in catalysis was further defined by the isolation of a radiolabeled phosphoenzyme intermediate, which identified a conserved histidine residue as the nucleophile in the catalytic reaction. Based on these data, a unifying two-step catalytic mechanism is proposed for this diverse family of enzymes. C1 Univ Michigan, Dept Biol Chem, Sch Med, Ann Arbor, MI 48109 USA. Univ Calif Davis, Sch Med, Dept Biol Chem, Davis, CA 95616 USA. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Univ Michigan, Dept Biol Chem, Sch Med, M5416 Med Sci Bldg I, Ann Arbor, MI 48109 USA. EM jedixon@umich.edu FU NIDDK NIH HHS [NIDDKD 18849] NR 34 TC 78 Z9 81 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 23 PY 1999 VL 274 IS 17 BP 11824 EP 11831 DI 10.1074/jbc.274.17.11824 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 188EX UT WOS:000079834800056 PM 10207000 ER PT J AU Chaika, OV Chaika, N Volle, DJ Hayashi, H Ebina, Y Wang, LM Pierce, JH Lewis, RE AF Chaika, OV Chaika, N Volle, DJ Hayashi, H Ebina, Y Wang, LM Pierce, JH Lewis, RE TI Mutation of tyrosine 960 within the insulin receptor juxtamembrane domain impairs glucose transport but does not inhibit ligand-mediated phosphorylation of insulin receptor substrate-2 in 3T3-L1 adipocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHOTYROSINE PROTEIN; SIGNAL-TRANSDUCTION; KINASE-ACTIVITY; CSF-1 RECEPTOR; CELLS; IRS-2; REGION; FAMILY; MICE; IDENTIFICATION AB CSF-1 is equipotent to insulin in its ability to stimulate 2[H-3]deoxyglucose uptake in 3T3-L1 adipocytes expressing the colony stimulating factor-1 receptor/insulin receptor chimera (CSF1R/IR), However, CSF-1-stimulated glucose uptake and glycogen synthesis is reduced by 50% in comparison to insulin in 3T3-L1 cells expressing a CSF1R/IR mutated at Tyr(960) (CSF1R/IRA960), CSF-1-treated adipocytes expressing the CSF1R/IRA960 were impaired in their ability to phosphorylate insulin receptor substrate 1 (IRS-1) but not in their ability to phosphorylate IRS-2, Immunoprecipitation of IRS proteins followed by Western blotting revealed that the intact CSF1R/IR co-precipitates with IRS-2 from CSF-1-treated cells. In contrast, the CSF1R/IRA960 co-precipitates poorly with IRS-S, These observations suggest that Tyr(960) is important for interaction of the insulin receptor cytoplasmic domain with IRS-2, but it is not essential to the ability of the insulin receptor tyrosine kinase to use IRS-2 as a substrate. These observations also suggest that in 3T3-L1 adipocytes, tyrosine phosphorylation of IRS-2 by the insulin receptor tyrosine kinase is not sufficient for maximal stimulation of receptor-regulated glucose transport or glycogen synthesis. C1 Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. Univ Tokushima, Inst Enzyme Res, Dept Enzyme Genet, Tokushima 770, Japan. NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Lewis, RE (reprint author), Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, 600 S 42nd St, Omaha, NE 68198 USA. FU NCI NIH HHS [P30 CA36727]; NIDDK NIH HHS [DK52809] NR 44 TC 11 Z9 13 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 APR 23 PY 1999 VL 274 IS 17 BP 12075 EP 12080 DI 10.1074/jbc.274.17.12075 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 188EX UT WOS:000079834800088 PM 10207032 ER PT J AU Huynh, CQ Zieler, H AF Huynh, CQ Zieler, H TI Construction of modular and versatile plasmid vectors for the high-level expression of single or multiple genes in insects and insect cell lines SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE transgenic insects; biolistics; electroporation; untranslated sequences ID DROSOPHILA-MELANOGASTER CELLS; DOMINANT SELECTABLE MARKER; NUCLEAR POLYHEDROSIS-VIRUS; YELLOW-FEVER MOSQUITO; HEAT-SHOCK PROMOTER; STABLE TRANSFORMATION; REGULATED EXPRESSION; MESSENGER-RNA; METALLOTHIONEIN GENE; LEPIDOPTERAN CELLS AB We have constructed a series of plasmid vectors for the expression of foreign genes in insects or insect cell lines. We incorporated the Drosophila hsp70 and actin 5C promoters, as well as the hr5 enhancer-driven baculovirus ie1 promoter, into plasmids that allow convenient cloning of heterologous genes into multiple cloning sites. We combined these promoters with either a short, double poly-adenylation site derived from the Heliothis virescens p63 chaperonin gene, or with a fusion of the small t intron with the early 3' untranslated region and poly-adenylation sites of SV40. Unique eight base cutter restriction sites flanking the promoters and poly-adenylation sequences make it possible to transfer the entire transcription units into other sequence contexts, for example, into transposable elements or into other plasmids bearing selectable marker genes. It is also convenient to combine two of our transcription units on the same plasmid in order to express multiple genes simultaneously. To test the ability of our vectors to drive expression of reporter genes, luciferase derivatives were made of the expression plasmids and introduced into Aedes albopictus C6/36 cells by electroporation or into Anopheles gambiae embryos by biolistic particle bombardment. All three promoters directed high levels of luciferase expression. However, there were differences in their relative activities in the two experimental systems. In C6/36 cells, the actin 5C and hr5-ie1 promoters were significantly more active than the hsp70 promoter. In Anopheles embryos, hsp70 and actin 5C had maximal activities, while hr5-ie1 was weaker. We also found that the constructs containing the SV40 small t intron and early 3' untranslated region sequences had higher expression levels than their counterparts containing the Heliothis poly-adenylation sequence. Our most active construct combines the actin 5C promoter with the SV40 intron and 3' untranslated region sequences. This vector was also used to drive expression of a visible marker, the enhanced green fluorescent protein gene, resulting in readily visible green fluorescent protein expression in C6/36 cells. (C) 1999 Academic Press. C1 NIAID, Med Entomol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Zieler, H (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 70 TC 36 Z9 38 U1 1 U2 5 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 APR 23 PY 1999 VL 288 IS 1 BP 13 EP 20 DI 10.1006/jmbi.1999.2674 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 189UZ UT WOS:000079925700002 PM 10329122 ER PT J AU Schaeffer, EM Debnath, J Yap, G McVicar, D Liao, XC Littman, DR Sher, A Varmus, HE Lenardo, MJ Schwartzberg, PL AF Schaeffer, EM Debnath, J Yap, G McVicar, D Liao, XC Littman, DR Sher, A Varmus, HE Lenardo, MJ Schwartzberg, PL TI Requirement for Tec kinases Rlk and Itk in T cell receptor signaling and immunity SO SCIENCE LA English DT Article ID TYROSINE KINASES; ANTIGEN RECEPTOR; PROTEIN-KINASE; TRANSDUCTION; PHOSPHORYLATION; RESISTANCE; ACTIVATION; FAMILY; MICE AB T cell receptor (TCR) signaling requires activation of Zap-70 and Src family tyrosine kinases, but requirements for other tyrosine kinases are Less clear. Combined deletion in;mice of two Tec kinases, Rlk and Itk, caused marked defects in TCR responses including proliferation, cytokine production, and apoptosis in vitro and adaptive:immune responses to Toxoplasma gondii in vivo. Molecular events immediately downstream from the TCR were intact in rlk(-/-)itk(-/-) cells, but intermediate events including inositol trisphosphate production, calcium mobilization, and mitogen-activated protein kinase activation were impaired, establishing Tec kinases as critical regulators of TCR signaling required for phospholipase C-gamma activation. C1 Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. Tularik, S San Francisco, CA 94080 USA. NYU, Med Ctr, Skirball Inst Biomol Med, New York, NY 10016 USA. RP Schwartzberg, PL (reprint author), Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. NR 21 TC 281 Z9 283 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 APR 23 PY 1999 VL 284 IS 5414 BP 638 EP 641 DI 10.1126/science.284.5414.638 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 190FH UT WOS:000079951100043 PM 10213685 ER PT J AU Berrueta, L Tirnauer, JS Schuyler, SC Pellman, D Bierer, BE AF Berrueta, L Tirnauer, JS Schuyler, SC Pellman, D Bierer, BE TI The APC-associated protein EB1 associates with components of the dynactin complex and cytoplasmic dynein intermediate chain SO CURRENT BIOLOGY LA English DT Article ID BINDING PROTEIN; MICROTUBULES; P150(GLUED); REVEALS; YEAST; ACTIN AB Human EB1 is a highly conserved protein that binds to the carboxyl terminus of the human adenomatous polyposis coli (APC) tumor suppressor protein [1], a domain of APC that is commonly deleted in colorectal neoplasia [2]. EB1 belongs to a family of microtubule-associated proteins that includes Schizosaccharomyces pombe Mal3 [3] and Saccharomyces cerevisiae Bim1p [4], Bim1p appears to regulate the timing of cytokinesis as demonstrated by a genetic interaction with Act5, a component of the yeast dynactin complex [5], Whereas the predominant function of the dynactin complex in yeast appears to be in positioning the mitotic spindle [6], in animal cells, dynactin has been shown to function in diverse processes, including organelle transport, formation of the mitotic spindle, and perhaps cytokinesis [7-10], Here, we demonstrate that human EB1 can be coprecipitated with p150(Glued), a member of the dynactin protein complex. EB1 was also found associated with the intermediate chain of cytoplasmic dynein (CDIC) and with dynamitin (p50), another component of the dynactin complex, but not with dynein heavy chain, in a complex that sedimented at approximately 5S in a sucrose density gradient. The association of EB1 with members of the dynactin complex was independent of APC and was preserved in the absence of an intact microtubule cytoskeleton, The molecular interaction of EB1 with members of the dynactin complex and with CDIC may be important for microtubule-based processes. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Bierer, BE (reprint author), NHLBI, 10 Ctr Dr, Bethesda, MD 20892 USA. OI Berrueta, Lisbeth/0000-0002-5674-6448 NR 17 TC 119 Z9 121 U1 1 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD APR 22 PY 1999 VL 9 IS 8 BP 425 EP 428 DI 10.1016/S0960-9822(99)80190-0 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 190BR UT WOS:000079942100019 PM 10226031 ER PT J AU Lin, ZW Neamati, N Zhao, H Kiryu, Y Turpin, JA Aberham, C Strebel, K Kohn, K Witvrouw, M Pannecouque, C Debyser, Z De Clercq, E Rice, WG Pommier, Y Burke, TR AF Lin, ZW Neamati, N Zhao, H Kiryu, Y Turpin, JA Aberham, C Strebel, K Kohn, K Witvrouw, M Pannecouque, C Debyser, Z De Clercq, E Rice, WG Pommier, Y Burke, TR TI Chicoric acid analogues as HIV-1 integrase inhibitors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 INTEGRASE; ZINC FINGERS; REPLICATION; PROTEIN; INVITRO; POTENT; ASSAY; AIDS; INFECTIVITY AB The present study was undertaken to examine structural features of L-chicoric acid (3) which are important for potency against purified HIV-1 integrase and for reported cytoprotective effects in cell-based systems. Through a progressive series of analogues, it was shown that enantiomeric D-chicoric acid (4) retains inhibitory potency against purified integrase equal to its L-counterpart and further that removal of either one or both carboxylic functionalities results in essentially no loss of inhibitory potency. Additionally, while two caffeoyl moieties are required, attachment of caffeoyl groups to the central linking structure can be achieved via amide or mixed amide/ester linkages. More remarkable is the finding that blockage of the catechol functionality through conversion to tetraacetate esters results in almost no loss of potency, contingent on the presence of at least one carboxyl group on the central linker. Taken as a whole, the work has resulted in the identification of new integrase inhibitors which may be regarded as bis-caffeoyl derivatives of glycidic acid and amino acids such as serine and beta-aminoalanine. The present study also examined the reported ability of chicoric acid to exert cytoprotective effects in HIV-infected cells. It was demonstrated in target and cell-based assays that the chicoric acids do not significantly inhibit other targets associated with HIV-1 replication, including reverse transcription, protease function, NCp7 zinc finger function, or replication of virus from latently infected cells. In CEM cells, for both the parent chicoric acid and selected analogues, antiviral activity was observable under specific assay conditions and with high dependence on the multiplicity of viral infection. However, against HIV-1- and HIV-2-infected MT-4 cells, the chicoric acids and their tetraacetylated esters exhibited antiviral activity (50% effective concentration (EC(50)) ranging from 1.7 to 20 mu M and 50% inhibitory concentration (IC(50)) ranging from 40 to 60 mu M). C1 NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NCI, Lab Antiviral Drug Mechanisms, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD 21702 USA. Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium. RP Burke, TR (reprint author), NCI, Med Chem Lab, Div Basic Sci, NIH, Bldg 37,Rm 5C06, Bethesda, MD 20892 USA. EM tburke@helix.nih.gov RI Burke, Terrence/N-2601-2014; OI debyser, zeger/0000-0002-3982-1565 NR 44 TC 118 Z9 122 U1 1 U2 9 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 APR 22 PY 1999 VL 42 IS 8 BP 1401 EP 1414 DI 10.1021/jm980531m PG 14 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 189RW UT WOS:000079920700010 PM 10212126 ER PT J AU Pettit, GR Toki, BE Herald, DL Boyd, MR Hamel, E Pettit, RK Chapuis, JC AF Pettit, GR Toki, BE Herald, DL Boyd, MR Hamel, E Pettit, RK Chapuis, JC TI Antineoplastic agents. 410. Asymmetric hydroxylation of trans-combretastatin A-4 SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID TUBULIN POLYMERIZATION; ANALOGS; ANGIOGENESIS; POTENT AB The South African willow tree Combretum caffrum has yielded a number of potent cancer cell growth inhibitors. The present SAR studies of the antineoplastic agent combretastatin A-4 (1c) were focused mainly on the olefinic bridge to determine the effects on cancer cell growth and, potentially, to better define the combretastatin A-4 binding site on tubulin. The geometric trans-isomer 3a of combretastatin A-4 was converted to the (1S,2S)- and (1R,2R)-vicinal diols 4c and 4d, respectively, under Sharpless' asymmetric dihydroxylation conditions. Cancer cell line testing showed the (1S,2S)-diol 4c to be more potent than its enantiomer 4d. Diol 4c weakly inhibited tubulin polymerization (IC50 = 22 mu M, versus 1.2 mu M for combretastatin A-4), while 4d was inactive (IC50 > 40 mu M). Esterification of either stereoisomer at the diol and/or phenolic positions resulted in elimination of inhibitory activity. C1 Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA. Arizona State Univ, Dept Chem, Tempe, AZ 85287 USA. NCI, Lab Drug Discovery Res & Dev, DTP DCTD, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Pettit, GR (reprint author), Arizona State Univ, Canc Res Inst, POB 872404, Tempe, AZ 85287 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NCI NIH HHS [CA 44344-05-9] NR 25 TC 62 Z9 63 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 22 PY 1999 VL 42 IS 8 BP 1459 EP 1465 DI 10.1021/jm9807149 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 189RW UT WOS:000079920700016 PM 10212132 ER PT J AU Mosterd, A D'Agostino, RB Silbershatz, H Sytkowski, PA Kannel, WB Grobbee, DE Levy, D AF Mosterd, A D'Agostino, RB Silbershatz, H Sytkowski, PA Kannel, WB Grobbee, DE Levy, D TI Trends in the prevalence of hypertension, antihypertensive therapy, and left ventricular hypertrophy from 1950 to 1989 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; BLOOD-PRESSURE; NATIONAL-HEALTH; ARTERY DISEASE; SECULAR TRENDS; SERIAL CHANGES; RISK-FACTORS; MORTALITY; CRITERIA; DECLINE AB Background Men and women with hypertension are at increased risk for cardiovascular disease, especially when left ventricular hypertrophy is present. We examined temporal trends in the use of antihypertensive medications and studied the relation between their use, the prevalence of high blood pressure, and the presence of electrocardiographic evidence of left ventricular hypertrophy. Methods A total of 10,333 participants in the Framingham Heart Study who were 45 to 74 years of age underwent a total of 51,756 examinations from 1950 to 1989. Data were obtained on blood pressure and the use of antihypertensive medications, and electrocardiograms were assessed for left ventricular hypertrophy. The generalized-estimating-equation method was used to test for trends over time. Results From 1950 to 1989, the rate of use of antihypertensive medications increased from 2.3 percent to 24.6 percent among men and from 5.7 percent to 27.7 percent among women. The age-adjusted prevalence of systolic blood pressure of at least 160 mm Hg or diastolic blood pressure of at least 100 mm Hg declined from 18.5 percent to 9.2 percent among men and from 28.0 percent to 7.7 percent among women. This decline was accompanied by age-adjusted reductions in the prevalence of electrocardiographic evidence of left ventricular hypertrophy, from 4.5 percent to 2.5 percent among men and from 3.6 percent to 1.1 percent among women. Conclusions Our findings support the notion that the increasing use of antihypertensive medication has resulted in a reduced prevalence of high blood pressure and a concomitant decline in left ventricular hypertrophy in the general population. Our observations may in part explain the considerable decline in mortality from cardiovascular disease observed since the late 1960s. (N Engl J Med 1999;340:1221-7) (C) 1999, Massachusetts Medical Society. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Erasmus Univ, Sch Med, Dept Epidemiol & Biostat, NL-3000 DR Rotterdam, Netherlands. Erasmus Univ, Thoraxctr, NL-3000 DR Rotterdam, Netherlands. Erasmus Univ, Div Cardiol, NL-3000 DR Rotterdam, Netherlands. Univ Utrecht, Julius Ctr Patient Oriented Res, Utrecht, Netherlands. NHLBI, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Div Epidemiol, Boston, MA USA. Boston Univ, Sch Med, Dept Math, Boston, MA 02118 USA. Boston Univ, Sch Med, Div Epidemiol & Prevent Med, Boston, MA 02118 USA. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. RI Grobbee, Diederick/C-7651-2014 OI Grobbee, Diederick/0000-0003-4472-4468 FU NHLBI NIH HHS [N01-HC-38038] NR 39 TC 189 Z9 197 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 22 PY 1999 VL 340 IS 16 BP 1221 EP 1227 DI 10.1056/NEJM199904223401601 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 188EL UT WOS:000079833800001 PM 10210704 ER PT J AU Merke, DP Tajima, T Baron, J Cutler, GB AF Merke, DP Tajima, T Baron, J Cutler, GB TI Hypogonadotropic hypogonadism in a female caused by an X-linked recessive mutation in the DAX1 gene SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ADRENAL HYPOPLASIA CONGENITA; KALLMANN SYNDROME; JAPANESE PATIENTS; HETEROGENEITY; CONVERSION; DIAGNOSIS; DNA C1 NICHD, DEB, NIH, Bethesda, MD 20892 USA. US PHS, Bethesda, MD USA. RP Merke, DP (reprint author), NICHD, DEB, NIH, Bldg 10,Rm 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. RI Toshihiro, Tajima/A-5720-2012 NR 23 TC 69 Z9 73 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 22 PY 1999 VL 340 IS 16 BP 1248 EP 1252 DI 10.1056/NEJM199904223401605 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 188EL UT WOS:000079833800005 PM 10210708 ER PT J AU Morell, RJ Friedman, TB AF Morell, RJ Friedman, TB TI Deafness and mutations in the connexin 26 gene - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Natl Inst Deafness & Other Commun Disorders, Rockville, MD 20850 USA. RP Morell, RJ (reprint author), Natl Inst Deafness & Other Commun Disorders, Rockville, MD 20850 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 22 PY 1999 VL 340 IS 16 BP 1288 EP 1288 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 188EL UT WOS:000079833800016 ER PT J AU Showstack, J Katz, PP Lake, JR Brown, RS Dudley, RA Belle, S Wiesner, RH Zetterman, RK Everhart, J AF Showstack, J Katz, PP Lake, JR Brown, RS Dudley, RA Belle, S Wiesner, RH Zetterman, RK Everhart, J CA NIDDK Liver Transplantation Database Grp TI Resource utilization in liver transplantation - Effects of patient characteristics and clinical practice SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID COST-EFFECTIVENESS; CYCLOSPORINE; CIRRHOSIS AB Context Liver transplantation is among the most costly of medical services, yet few studies have addressed the relationship between the resources utilized for this procedure and specific patient characteristics and clinical practices. Objective To assess the association of pretransplant patient characteristics and clinical practices with hospital resource utilization. Design Prospective cohort of patients who received liver transplants between January 1991 and July 1994. Setting University of California, San Francisco; Mayo Clinic, Rochester, Minn; and the University of Nebraska, Omaha, Patients Seven hundred eleven patients who received single-organ liver transplants, were at least 16 years old, and had nonfulminant liver disease. Main Outcome Measure Standardized resource utilization derived from a database created by matching all services to a single price list. Results Higher adjusted resource utilization was associated with donor age of 60 years or older (28% [$53 813] greater mean resource utilization; P=.005); recipient age of 60 years or older (17% [$32 795]; P=.01); alcoholic liver disease (26% [$49 596]; P=.002); Child-Pugh class C (41% [$67 658]; P<.001); care from the intensive care unit at time of transplant (42% [$77 833]; P<.001); death in the hospital (35% [$67 076]; P<.001); and having multiple liver transplants during the index hospitalization (154% increase [$474 740 vs $186 726 for 1 transplant]; P<.001). Adjusted length of stay and resource utilization also differed significantly among transplant centers. Conclusions Clinical, economic, and ethical dilemmas in liver transplantation are highlighted by these findings. Recipients who were older, had alcoholic liver disease, or were severely ill were the most expensive to treat; this suggests that organ allocation criteria may affect transplant costs. Clinical practices and resource utilization varied considerably among transplant centers; methods to reduce variation in practice patterns, such as clinical guidelines, might lower costs while maintaining quality of care. C1 Univ Calif San Francisco, Inst Hlth Policy Studies, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Liver Transplant Program, San Francisco, CA 94143 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Mayo Clin, Dept Med, Rochester, MN USA. Univ Nebraska, Dept Med, Omaha, NE 68182 USA. NIDDKD, Branch Epidemiol & Clin Trials, Bethesda, MD 20892 USA. RP Showstack, J (reprint author), Univ Calif San Francisco, Inst Hlth Policy Studies, Dept Med, San Francisco, CA 94143 USA. EM jas1@itsa.ucsf.edu RI Showstack, Jonathan/L-6556-2013 OI Showstack, Jonathan/0000-0002-1367-419X FU NIDDK NIH HHS [N01-DK-0-2251, N01-DK-0-2252, N01-DK-0-2253] NR 30 TC 142 Z9 143 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 21 PY 1999 VL 281 IS 15 BP 1381 EP 1386 DI 10.1001/jama.281.15.1381 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 185ZF UT WOS:000079701000027 PM 10217053 ER PT J AU Levine, M Rumsey, SC Daruwala, R Park, JB Wang, YH AF Levine, M Rumsey, SC Daruwala, R Park, JB Wang, YH TI Criteria and recommendations for vitamin C intake SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID CORONARY HEART-DISEASE; ASCORBIC-ACID SUPPLEMENTATION; DEHYDROASCORBIC ACID; UNITED-STATES; ANTIOXIDANT VITAMINS; HUMAN NEUTROPHILS; OXIDATIVE STRESS; CARDIOVASCULAR-DISEASE; MACULAR DEGENERATION; CHRONIC-HEMODIALYSIS AB Recommendations for vitamin C intake are under revision by the Food and Nutrition Board of the National Academy of Sciences, Since 1989 when the last recommended dietary allowance (RDA) of 60 mg was published, extensive biochemical, molecular, epidemiologic, and clinical data have become available. New recommendations can be based on the following 9 criteria: dietary availability, steady-state concentrations in plasma in relationship to dose, steady-state concentrations in tissues in relationship to dose, bioavailability, urine excretion, adverse effects, biochemical and molecular function in relationship to vitamin concentration, direct beneficial effects and epidemiologic observations in relationship to dose, and prevention of deficiency, We applied these criteria to the Food and Nutrition Board's new guidelines, the Dietary Reference Intakes, which include 4 reference values, The estimated average requirement (EAR) is the amount of nutrient estimated to meet the requirement of half the healthy individuals in a life-stage and gender group, Based on an EAR of 100 mg/d of vitamin C, the RDA is proposed to be 120 mg/d, If the EAR cannot be determined, an adequate intake (AI) amount is recommended instead of an RDA. The AI was estimated to be either 200 mg/d from 5 servings of fruits and vegetables or 100 mg/d of vitamin C to prevent deficiency with a margin of safety, The final classification, the tolerable upper intake level, is the highest daily level of nutrient intake that does not pose risk or adverse health effects to almost all individuals in the population. This amount is proposed to be less than 1 g of vitamin C daily. Physicians can tell patients that 5 servings of fruits and vegetables per day may be beneficial in preventing cancer and providing sufficient vitamin C intake for healthy people, and that 1 g or more of vitamin C may have adverse consequences in some people. C1 NIDDKD, Mol & Clin Nutr Sect, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. USDA, Beltsville Human Nutr Res Ctr, Phytonutrients Lab, Beltsville, MD 20705 USA. RP Levine, M (reprint author), NIDDKD, Mol & Clin Nutr Sect, Digest Dis Branch, NIH, Bldg 10,Room 4D52, Bethesda, MD 20892 USA. NR 106 TC 233 Z9 239 U1 3 U2 25 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 APR 21 PY 1999 VL 281 IS 15 BP 1415 EP 1423 DI 10.1001/jama.281.15.1415 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 185ZF UT WOS:000079701000032 PM 10217058 ER PT J AU Wingo, PA Ries, LAG Giovino, GA Miller, DS Rosenberg, HM Shopland, DR Thun, MJ Edwards, BK AF Wingo, PA Ries, LAG Giovino, GA Miller, DS Rosenberg, HM Shopland, DR Thun, MJ Edwards, BK TI Annual report to the nation on the status of cancer, 1973-1996, with a special section on lung cancer and tobacco smoking SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CURRENT POPULATION SURVEY; CIGARETTE-SMOKING; UNITED-STATES; PREVALENCE; MORTALITY; EXPOSURE; TRENDS; ADULTS; STRAW; YOUTH AB Background: The American Cancer Society, the National Cancer Institute (NCI), and the Centers for Disease Control and Prevention (CDC), including the National Center for Health Statistics (NCHS), provide the second annual report to the nation on progress in cancer prevention and control, with a special section on lung cancer and tobacco smoking. Methods: Age-adjusted rates (using the 1970 U.S. standard population) were based on cancer incidence data from NCI and underlying cause of death data compiled by NCHS, The prevalence of tobacco use was derived from CDC surveys, Reported P values are two-sided. Results: From 1990 through 1996, cancer incidence (-0.9% per year; P = .16) and cancer death (-0.6% per year; P = .001) rates for all sites combined decreased. Among the 10 leading cancer incidence sites, statistically significant decreases in incidence rates were seen in males for leukemia and cancers of the lung, colon/rectum, urinary bladder, and oral cavity and pharynx, Except for lung cancer, incidence rates for these cancers also declined in females. Among the 10 leading cancer mortality sites, statistically significant decreases in cancer death rates were seen for cancers of the male lung, female breast, the prostate, male pancreas, and male brain and, for both sexes, cancers of the colon/rectum and stomach. Age-specific analyses of lung cancer revealed that rates in males first declined at younger ages and then for each older age group successively over time; rates in females appeared to be in the early stages of following the same pattern, with rates decreasing for women aged 40-59 years. Conclusions: The declines in cancer incidence and death rates, particularly for lung cancer, are encouraging. However, unless recent upward trends in smoking among adolescents can be reversed, the lung cancer rates that are currently declining in the United States may rise again. 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 Chron Dis Prevent & Hlth Promot, Div Canc Prevent & Control, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Vital Stat, Hyattsville, MD 20782 USA. Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. RP Wingo, PA (reprint author), Amer Canc Soc, Epidemiol & Surveillance Res Dept, 1599 Clifton Rd NE, Atlanta, GA 30329 USA. EM pwingo@cancer.org NR 91 TC 416 Z9 428 U1 2 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 21 PY 1999 VL 91 IS 8 BP 675 EP 690 DI 10.1093/jnci/91.8.675 PG 16 WC Oncology SC Oncology GA 190AA UT WOS:000079938300008 PM 10218505 ER PT J AU Lam, S LeRiche, JC Zheng, Y Coldman, A MacAulay, C Hawk, E Kelloff, G Gazdar, AF AF Lam, S LeRiche, JC Zheng, Y Coldman, A MacAulay, C Hawk, E Kelloff, G Gazdar, AF TI Sex-related differences in bronchial epithelial changes associated with tobacco smoking SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID FORCED EXPIRATORY VOLUME; LUNG-CANCER MORTALITY; FORMER SMOKERS; FLUORESCENCE BRONCHOSCOPY; CIGARETTE-SMOKING; ONE 2ND; RISK; DYSPLASIA; SPUTUM; LOCALIZATION AB Background: Lung cancer is the most common cause of cancer death in North American women, Because smoking-related changes in the bronchial epithelium and in lung function have not been studied in detail in women, we used fluorescence bronchoscopy-directed biopsy to determine the prevalence of high-grade preinvasive lesions in former and current smokers of both sexes. Methods: Spirometry, white-light bronchoscopy, and fluorescence bronchoscopy were performed in 189 women and 212 men older than 40 years of age who had smoked 20 pack-years or more (pack-years number of packs of cigarettes smoked per day x number of years of smoking). Results: Carcinoma in situ was found in 1.8% of the subjects, severe dysplasia was found in 6.5%, and moderate dysplasia was found in 14% (all preinvasive lesions). Compared with men, women had a lower prevalence of high-grade preinvasive lesions in the observed airways (14% versus 31%; odds ratio = 0.18; 95% confidence interval = 0.04-0.88), and women with preinvasive lesions had fewer such lesions (two-sided P = .048), The prevalence of preinvasive lesions did not change substantially for more than 10 years after cessation of smoking. Lung function was associated with the prevalence of preinvasive lesions, but the association was weaker in women than in men, If the presence of airflow obstruction was defined by an FEV1/FVC (forced expiratory volume in 1 second/forced vital capacity) value of 70% or less, only 56% of the men and 44% of the women with preinvasive lesions had abnormal lung function. Conclusion: In developing strategies for chemoprevention or early detection of lung cancer in high-risk populations, it is important to consider the effect of sex and arbitrarily chosen lung function values on the prevalence of preinvasive airway lesions. C1 British Columbia Canc Agcy, Dept Resp Med, Vancouver, BC V5Z 3J5, Canada. Univ British Columbia, Vancouver, BC V5Z 3J5, Canada. British Columbia Canc Agcy, Dept Pathol, Vancouver, BC V5Z 3J5, Canada. British Columbia Canc Agcy, Dept Canc Imaging, Vancouver, BC V5Z 3J5, Canada. British Columbia Canc Agcy, Dept Canc Prevent, Vancouver, BC V5Z 3J5, Canada. NCI, Chemoprevent Branch, Div Canc Prevent, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX USA. RP Lam, S (reprint author), British Columbia Canc Agcy, Dept Resp Med, 2775 Heather St, Vancouver, BC V5Z 3J5, Canada. FU NCI NIH HHS [N01CN65030, U01CA68381] NR 39 TC 67 Z9 71 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 APR 21 PY 1999 VL 91 IS 8 BP 691 EP 696 DI 10.1093/jnci/91.8.691 PG 6 WC Oncology SC Oncology GA 190AA UT WOS:000079938300009 PM 10218506 ER PT J AU Frisch, M Glimelius, B Wohlfahrt, J Adami, HO Melbye, M AF Frisch, M Glimelius, B Wohlfahrt, J Adami, HO Melbye, M TI Tobacco smoking as a risk factor in anal carcinoma: an antiestrogenic mechanism? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CIGARETTE-SMOKING; CANCER; RECEPTORS; WOMEN; PROGESTERONE; EPITHELIUM; ESTROGEN AB Background: Human papillomavirus-associated anogenital carcinogenesis depends on poorly defined cofactors. Smoking was recently suggested to increase the risk of anal cancer more in premenopausal women than in postmenopausal women. Thus, we used our population-based anal cancer case-control study in Denmark and Sweden to test this hypothesis. Methods: Our study included 417 patients (324 women and 93 men) who were diagnosed with anal cancer (84% invasive cancer) from 1991 through 1994;:it also included five patients diagnosed in 1995. Two control groups were used: 1) 554 population control subjects (349 women and 205 men) and 2) 534 patients with rectal adenocarcinoma (343 women and 191 men). Odds ratios (ORs), calculated from logistic regression analyses, were used as measures of relative risk. All P values are two-sided. Results: Compared with the risk for lifelong nonsmokers, the risk of anal cancer was high among premenopausal women who currently smoked tobacco (multivariate OR = 5.6; 95% confidence interval [CI] = 2.4-12.7) and increased linearly by 6.7% per pack-year smoked tone pack-year is equivalent to one pack of cigarettes smoked per day for 1 year) (P for trend <.001), Smoking was not statistically significantly associated with anal cancer risk in postmenopausal women or men. Women whose menstrual periods started late were at high risk (multivariate OR = 3.6; 95% CI = 1.8-7.3, for greater than or equal to 17 years of age versus less than or equal to 12 years of age; P for trend <.001), and body mass index (weight in kg/[height in m](2)) was inversely associated with risk among women (P<.001), Conclusions: Because the risk of anal cancer associated with smoking was restricted to premenopausal women and because higher risk was associated with late menarche and lean body composition, female sex hormones may be a factor in anal cancer development in women. Since the anal mucosa is an estrogen-sensitive area, we hypothesize an antiestrogenic mechanism of action for smoking in anal carcinogenesis. C1 Danish Epidemiol Sci Ctr, Dept Epidemiol Res, Statens Serum Inst, Copenhagen, Denmark. Univ Uppsala Hosp, Dept Oncol Radiol & Clin Immunol, Uppsala, Sweden. Karolinska Inst, Dept Med Epidemiol, Stockholm, Sweden. Harvard Univ, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Harvard Ctr Canc Prevent, Boston, MA 02115 USA. RP Frisch, M (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Execut Plaza S,Rm 8015, Bethesda, MD 20892 USA. RI Frisch, Morten/E-9206-2016 OI Frisch, Morten/0000-0002-3864-8860 NR 20 TC 42 Z9 47 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 APR 21 PY 1999 VL 91 IS 8 BP 708 EP 715 DI 10.1093/jnci/91.8.708 PG 8 WC Oncology SC Oncology GA 190AA UT WOS:000079938300012 PM 10218509 ER PT J AU Wray, V Kinder, R Federau, T Henklein, P Bechinger, B Schubert, U AF Wray, V Kinder, R Federau, T Henklein, P Bechinger, B Schubert, U TI Solution structure and orientation of the transmembrane anchor domain of the HTV-1-encoded virus protein U by high-resolution and solid-state NMR spectroscopy SO BIOCHEMISTRY LA English DT Article ID TYPE-1 VPU PROTEIN; CHEMICAL-SHIFT TENSORS; ION-CHANNEL ACTIVITY; NUCLEAR-MAGNETIC-RESONANCE; INTEGRAL MEMBRANE-PROTEIN; F1F0 ATP SYNTHASE; CYTOPLASMIC DOMAIN; HIV-1 VPU; SECONDARY STRUCTURE; N-15 NMR AB The structure of the membrane anchor domain (Vpu(MA)) of the HIV-1-specific accessory protein Vpu has been investigated in solution and in lipid bilayers by homonuclear two-dimensional and solid-state nuclear magnetic resonance spectroscopy, respectively. Simulated annealing calculations, using the nuclear Overhauser enhancement data for the soluble synthetic peptide Vpu(1-39) (positions Met-1-Asp-39) in an aqueous 2,2,2-trifluoroethanol (TFE) solution, afford a compact well-defined U-shaped structure comprised of an initial turn (residues 1-6) followed by a linker (7-9) and a short helix on the N-terminal side (10-16) and a further longer helix on the C-terminal side (22-36). The side chains of the two aromatic residues (Trp-22 and Tyr-29) in the longer helix are directed toward the center of the molecule around which the hydrophobic core of the folded Vpu(MA) is positioned. As the observed solution structure is inconsistent with the formation of ion-conductive membrane pores defined previously for Vpu(MA) in planar lipid bilayers, the isolated Vpu(MA) domain as peptide Vpu(1-27) was investigated in oriented phospholipid bilayers by proton-decoupled N-15 cross polarization solid-stare NMR spectroscopy. The Line widths and chemical shift data of three selectively N-15-labeled peptides are consistent with a transmembrane alignment of a helical polypeptide. Chemical shift tensor calculations imply that the data sets are compatible with a model in which the nascent helices of the folded solution structure reassemble to form a more regular linear alpha-helix that lies parallel to the bilayer normal with a tilt angle of less than or equal to 30 degrees. The arrangement of the membrane-associated structures described previously for the cytoplasmic domain and for the anchor domain of Vpu identified in this work is discussed. C1 Gesell Biotechnol Forsch mbH, GBF, Abt Strukturforsch, Dept Mol Struct Res, D-38124 Braunschweig, Germany. Bereich Strukturforsch, Max Planck Inst Biochem, D-82152 Martinsried, Germany. Humboldt Univ, Inst Biochem, Berlin, Germany. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Hamburg, Heinrich Pette Inst Expt Virol, Hamburg, Germany. RP Wray, V (reprint author), Gesell Biotechnol Forsch mbH, GBF, Abt Strukturforsch, Dept Mol Struct Res, Mascheroder Weg 1, D-38124 Braunschweig, Germany. EM vwr@gbf.de; bechinge@alf.biochem.mpg.de NR 71 TC 66 Z9 66 U1 1 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 APR 20 PY 1999 VL 38 IS 16 BP 5272 EP 5282 DI 10.1021/bi982755c PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 189UL UT WOS:000079924500045 PM 10213635 ER PT J AU Pinsuwan, S Alvarez-Nunez, FA Tabibi, ES Yalkowsky, SH AF Pinsuwan, S Alvarez-Nunez, FA Tabibi, ES Yalkowsky, SH TI Degradation kinetics of 4-dedimethylamino sancycline, a new anti-tumor agent, in aqueous solutions SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE 4-dedimethylamino sancycline; anti-tumor agent; aqueous solutions ID PERFORMANCE LIQUID-CHROMATOGRAPHY; TETRACYCLINE AB The kinetics of degradation of the new anti-tumor drug, 4-dedimethylamino sancycline (col-3) in aqueous solution at 25 degrees C were investigated by high-pressure liquid chromatography (HPLC) over the pH-range of 2-10. The influences of pH, buffer concentration, light, temperature, and some additives on the degradation rate were studied. The degradation of col-3 was found to follow first order kinetics. A rate expression covering the degradation of the various ionic forms of the drug was derived and shown to account for the shape of the experimental pH-rate profile. Under basic conditions, the degradation of col-3 involves oxidation, which is catalyzed by metal ions and inhibited by EDTA and Sodium bisulfite. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Arizona, Coll Pharm, Dept Pharm Practice & Sci, Tucson, AZ 85721 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Yalkowsky, SH (reprint author), Univ Arizona, Coll Pharm, Dept Pharm Practice & Sci, 1703 E Mabel St,POB 210207, Tucson, AZ 85721 USA. FU NCI NIH HHS [N01-CM-27757] NR 32 TC 10 Z9 10 U1 0 U2 2 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 APR 20 PY 1999 VL 181 IS 1 BP 31 EP 40 DI 10.1016/S0378-5173(98)00417-7 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 201TA UT WOS:000080610600004 PM 10370200 ER PT J AU Radko, SP Chrambach, A AF Radko, SP Chrambach, A TI Electrophoretic migration of submicron polystyrene latex spheres in solutions of linear polyacrylamide SO MACROMOLECULES LA English DT Article ID ENTANGLED POLYMER-SOLUTIONS; CAPILLARY ELECTROPHORESIS; PROBE DIFFUSION; GEL-ELECTROPHORESIS; COMPACT PARTICLES; LIGHT-SCATTERING; DEPLETION LAYERS; INTERFACES; DEXTRAN; WATER AB The electrophoretic migration of highly cross-linked carboxylated polystyrene latex spheres of 55, 140, and 215 nm radius (R) in solutions of linear polyacrylamide of 0.4 x 10(6), 0.6 x 10(6), and 1 x 10(6) molecular weight, in the 0.1-1% concentration range, was studied by capillary zone electrophoresis. The electric field strengths applied ranged from 40 to 530 V/cm. At the ionic strength used, these particles must be considered "large", exhibiting kappa R greater than or equal to 13 where kappa(-1) is the thickness of electric double layer. In the semidilute polymer concentration regime, the radius of the particles severalfold exceeds the average mesh size, xi, in the polymer network. It was found that particle retardation (expressed as mu/mu(0) where mu and mu(0) are particle electrophoretic mobilities in polymer solution and buffer alone) at a given polymer concentration decreases with both increasing particle size and electric field strength but increases with polymer molecular weight. The dependence of retardation on polymer concentration, c, follows a "stretched exponent", mu/mu(0) = exp(-alpha c''). The prefactor a and the exponent nu are particle radius and electric field strength dependent. The microviscosity of polymer solutions defined as mu(0)/mu was well below values of zero shear viscosity measured viscometrically even when no dependence of microviscosity on electric field strength was observed. These findings were interpreted in terms of (i) a local shearlike deformation of the polymer network upon particle passage, resulting in a progressive decrease of the network entanglement density at the particle locales with particle translational velocity and, thus, a decrease of network resistance to particle penetration; and (ii) a progressive polymer depletion near the particle surface, with increasing particle radius at the scale of R/xi, which facilitates electrophoretic migration of the microparticle in the polymer solutions. C1 NICHHD, Macromol Anal Sect, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Chrambach, A (reprint author), NICHHD, Macromol Anal Sect, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. NR 58 TC 16 Z9 16 U1 2 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0024-9297 J9 MACROMOLECULES JI Macromolecules PD APR 20 PY 1999 VL 32 IS 8 BP 2617 EP 2628 DI 10.1021/ma9814447 PG 12 WC Polymer Science SC Polymer Science GA 188QU UT WOS:000079860400029 ER PT J AU Pinney, KG Bounds, AD Dingeman, KM Mocharla, VP Pettit, GR Bai, R Hamel, E AF Pinney, KG Bounds, AD Dingeman, KM Mocharla, VP Pettit, GR Bai, R Hamel, E TI A new anti-tubulin agent containing the benzo[b]thiophene ring system SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID ENDOGENOUS MAMMALIAN METABOLITE; ANTIMITOTIC NATURAL-PRODUCTS; 1ST TOTAL SYNTHESIS; ESTROGEN-RECEPTOR; ARYL AZIDE; CONFORMATIONAL-ANALYSIS; ANTINEOPLASTIC AGENTS; ANTITUMOR MACROLIDE; ANTICANCER AGENTS; POLYMERIZATION AB A new type of inhibitor of tubulin polymerization was discovered based on the 3-aroyl-2-arylbenzo[b]thiophene molecular skeleton. The lead compound in this series, 2-(4'-methoxyphenyl)-3-(3',4',5'-trimethoxybenzoyl)-6-methoxybenzo[b]thio 1, inhibited tubulin polymerization, caused an increase in the mitotic index of CA46 Burkitt lymphoma cells, and inhibited the growth of several human cancer cell lines. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Baylor Univ, Dept Chem, Waco, TX 76798 USA. Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA. Arizona State Univ, Dept Chem, Tempe, AZ 85287 USA. NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Proram,Div Canc Treatment & Diag, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. RP Pinney, KG (reprint author), Baylor Univ, Dept Chem, POB 97348, Waco, TX 76798 USA. OI Pinney, Kevin/0000-0003-1262-8631 FU NCI NIH HHS [CA-44344-06-10] NR 33 TC 95 Z9 95 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD APR 19 PY 1999 VL 9 IS 8 BP 1081 EP 1086 DI 10.1016/S0960-894X(99)00143-2 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 191VF UT WOS:000080041700003 PM 10328289 ER PT J AU Ashman, SB Monk, TH Kupfer, DJ Clark, CH Myers, FS Frank, E Leibenluft, E AF Ashman, SB Monk, TH Kupfer, DJ Clark, CH Myers, FS Frank, E Leibenluft, E TI Relationship between social rhythms and mood in patients with rapid cycling bipolar disorder SO PSYCHIATRY RESEARCH LA English DT Article DE affective disorder; rapid cycling; social rhythm; circadian; zeitgeber ID SLEEP-WAKE CYCLE; CIRCADIAN-RHYTHMS; PHASE-ADVANCE; DEPRESSION; LIFE; DEPRIVATION; REGULARITY; THERAPY AB Disruptions in the sleep-wake cycle frequently characterize affective illness and have led to a number of theories linking sleep-wake and/or circadian rhythm disturbance to affective illness. Recently, researchers have expanded these chronobiological theories to include the role of lifestyle regularity, or daily social rhythms. In this study, the Social Rhythm Metric (SRM) was used to explore the relationship between social rhythms and mood in patients with rapid cycling bipolar disorder and to compare the social rhythms of patients with those of healthy control subjects. Patients' SRM scores and activity level indices were significantly lower than those of control subjects. In addition, the timing of five, mostly morning, activities was phase delayed in patients compared to control subjects. Patients also demonstrated a phase delay in the timing of morning activities during depression compared to hypomania or euthymia. The phase changes in the timing of morning activities are consistent with other data implicating morning zeitgebers in the pathophysiology of rapid cycling bipolar disorder. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 NIMH, Clin Psychobiol Branch, Bethesda, MD 20892 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Western Psychiat Inst & Clin, Pittsburgh, PA USA. NIMH, Pediat & Dev Neuropsychiat Branch, Bethesda, MD 20892 USA. RP Ashman, SB (reprint author), Univ Washington, Dept Psychol, Box 351525, Seattle, WA 98195 USA. FU NIMH NIH HHS [MH30915] NR 27 TC 57 Z9 57 U1 2 U2 8 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 APR 19 PY 1999 VL 86 IS 1 BP 1 EP 8 DI 10.1016/S0165-1781(99)00019-0 PG 8 WC Psychiatry SC Psychiatry GA 198PT UT WOS:000080433700001 PM 10359478 ER PT J AU Schwartz, PJ Turner, EH Garcia-Borreguero, D Sedway, J Vetticad, RG Wehr, TA Murphy, DL Rosenthal, NE AF Schwartz, PJ Turner, EH Garcia-Borreguero, D Sedway, J Vetticad, RG Wehr, TA Murphy, DL Rosenthal, NE TI Serotonin hypothesis of winter depression: behavioral and neuroendocrine effects of the 5-HT1A receptor partial agonist ipsapirone in patients with seasonal affective disorder and healthy control subjects SO PSYCHIATRY RESEARCH LA English DT Review DE 5-HT1A receptors; seasonal affective disorder; ipsapirone; cortisol; prolactin; adrenocorticotropic hormone; ACTH ID CORTICOTROPIN-RELEASING HORMONE; OBSESSIVE-COMPULSIVE DISORDER; LIGHT THERAPY; META-CHLOROPHENYLPIPERAZINE; TRYPTOPHAN DEPLETION; CORTISOL SECRETION; NEURO-ENDOCRINE; M-CPP; BUSPIRONE CHALLENGE; RETINAL PROJECTION AB Winter depressions in seasonal affective disorder (SAD) are associated with central serotonergic (5-HT) dysfunction. SAD patients demonstrate rather specific, state-dependent, abnormal increases in 'activation-euphoria' ratings following intravenous infusion of the 5-HT receptor agonist meta-chlorophenylpiperazine (m-CPP). Several studies are also consistent with abnormal serotonergic regulation of the hypothalamic-pituitary-adrenal (HPA) axis in SAD. Here, we investigated the effects of the 5-HT1A receptor partial agonist ipsapirone, which produces behavioral effects and HPA-axis activation, to further characterize the 5-HT receptor subtype-specificity of these disturbances in SAD. Eighteen SAD patients and 18 control subjects completed two drug challenges (ipsapirone 0.3 mg/kg and placebo) separated by 3-5 days in randomized order. We measured behavioral responses with the NIMH self-rating scale, and plasma ACTH, cortisol, and prolactin concentrations. Compared with placebo, ipsapirone was associated with significant increases in self-rated 'functional deficit' and 'altered self-reality', and in each of the hormones. There were no differences between groups on any measures. The level of depression in SAD patients was inversely correlated with their ipsapirone-induced cortisol responses. There were significant drug x order effects on baseline 'anxiety' scores, ACTH and cortisol concentrations, such that subjects were significantly more stressed (higher 'anxiety', ACTH and cortisol) prior to their first challenge compared with their second. In conclusion, post-synaptic 5-HT1A receptors appear to function normally in SAD. The previously observed m-CPP-induced behavioral abnormality may be mediated by either 5-HT2C or 5-HT7 receptors. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH USA. VAMC, Cincinnati, OH USA. Food & Drug Adm, Rockville, MD USA. NIMH, Sect Biol Rhythms, Bethesda, MD 20892 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Schwartz, PJ (reprint author), 787 Ludlow Ave 2, Cincinnati, OH 45220 USA. RI Turner, Erick/A-4848-2008 OI Turner, Erick/0000-0002-3522-3357 NR 109 TC 22 Z9 24 U1 0 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 APR 19 PY 1999 VL 86 IS 1 BP 9 EP 28 DI 10.1016/S0165-1781(99)00017-7 PG 20 WC Psychiatry SC Psychiatry GA 198PT UT WOS:000080433700002 PM 10359479 ER PT J AU Clarke, RA Murphy, DL Constantino, JN AF Clarke, RA Murphy, DL Constantino, JN TI Serotonin and externalizing behavior in young children SO PSYCHIATRY RESEARCH LA English DT Article DE 5-hydroxyindoleacetic acid (5-HIAA); aggression; family environment ID CEREBROSPINAL-FLUID MONOAMINE; ANTISOCIAL PERSONALITY-DISORDER; LOW CSF 5-HIAA; RHESUS-MONKEYS; AGGRESSIVE-BEHAVIOR; 5-HYDROXYINDOLEACETIC ACID; REUPTAKE INHIBITORS; CIRCUMPLEX MODEL; SOCIAL-BEHAVIOR; FAMILY HISTORY AB Considerable evidence suggests that there is a relationship between pathologic aggressive behavior and low cerebrospinal fluid (CSF) concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in both humans and non-human primates. The purpose of this investigation is to examine the relationship between CSF concentrations of human newborn 5-HIAA and subsequent aggressive behavior observed at 30 months of age. Leftover portions of culture negative CSF drawn from febrile infants (age, birth to 3 months) were assayed for 5-HIAA. Family environment and child behavior were assessed at 30 months by parent report. Subjects with 5-HIAA levels below the median of the distribution had higher externalizing behavior scores at 30 months than did subjects whose 5-HIAA levels fell above the median (P = 0.02). While it is likely that serotonin mediates one component of genetic liability to antisocial outcome, the magnitude of that component may be less than what has been inferred from previously published reports. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. RP Constantino, JN (reprint author), Washington Univ, Sch Med, Dept Psychiat, 4940 Childrens Pl, St Louis, MO 63110 USA. FU NIMH NIH HHS [1R03MH56317-01] NR 63 TC 27 Z9 27 U1 2 U2 5 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 APR 19 PY 1999 VL 86 IS 1 BP 29 EP 40 DI 10.1016/S0165-1781(99)00022-0 PG 12 WC Psychiatry SC Psychiatry GA 198PT UT WOS:000080433700003 PM 10359480 ER PT J AU Kuritzkes, DR Marschner, I Johnson, VA Bassett, R Eron, JJ Fischl, MA Murphy, RL Fife, K Maenza, J Rosandich, ME Bell, D Wood, K Sommadossi, JP Pettinelli, C AF Kuritzkes, DR Marschner, I Johnson, VA Bassett, R Eron, JJ Fischl, MA Murphy, RL Fife, K Maenza, J Rosandich, ME Bell, D Wood, K Sommadossi, JP Pettinelli, C CA Natl Inst Allergy Infect Dis AIDS Clinical Tria TI Lamivudine in combination with zidovudine stavudine, or didanosine in patients with HIV-1 infection. A randomized, double-blind, placebo-controlled trial SO AIDS LA English DT Article; Proceedings Paper CT 5th Conference on Retroviruses and Opportunistic Infections CY FEB 01-05, 1998 CL CHICAGO, ILLINOIS DE HIV; lamivudine; zidovudine; stavudine; combination therapy; antiretroviral therapy ID IMMUNODEFICIENCY-VIRUS TYPE-1; CUBIC MILLIMETER; PLUS LAMIVUDINE; REVERSE-TRANSCRIPTASE; THERAPY; RESISTANT; MONOTHERAPY; EFFICACY; NAIVE; CHILDREN AB Objective: To study the antiviral activity of lamivudine (3TC) plus zidovudine (ZDV), didanosine (ddl), or stavudine (d4T). Design: Randomized, placebo-controlled, partially double-blinded multicenter study. Setting: Adult AIDS Clinical Trials Units. Patients: Treatment-naive HIV-infected adults with 200-600 x 10(6) CD4 T lymphocytes/l. Interventions: Patients were openly randomized to a d4T or a ddl limb, then randomized in a blinded manner to receive: d4T (80 mg/day), d4T plus 3TC (300 mg/day), or ZDV (600 mg/day) plus 3TC, with matching placebos; or ddl (400 mg/day), ddl plus 3TC (300 mg/day), or ZDV (600 mg/day) plus 3TC, with matching placebo. After 21 weeks 3TC was added for patients assigned to the monotherapy arms. Main outcome measure: The reduction in plasma HIV-1 RNA level at weeks 24 and 48. Results: Two hundred ninety-nine patients were enrolled. After 24 weeks the mean reduction in plasma HIV-1 RNA copies/ml from baseline was 0.49 log(10) (d4T monotherapy) versus 1.03 log(10) (d4T plus 3TC; P = 0.001), and 0.68 log(10) (ddl monotherapy) versus 0.82 log(10) (ddl plus 3TC; P > 0.22), After 38 weeks the mean reduction was 1.08 log(10) (d4T plus 3TC) versus 1.01 log(10) (ZDV plus 3TC) in the d4T limb (P = 0.66), and 0.94 log(10) (ddl plus 3TC) versus 0.88 log(10) (ZDV plus 3TC; P = 0.70) in the ddl limb. Conclusions: 3TC added significantly to the virologic effects of d4T, but not ddl, in treatment-naive patients 3TC plus d4T produced virologic changes comparable to those of 3TC plus ZDV. These results support the use of 3TC with either ZDV or d4T as a component of initial combination antiretroviral therapy. (C) 1999 Lippincott Williams & Wilkins. C1 Univ Colorado, Hlth Sci Ctr, Div Infect Dis, Denver, CO 80262 USA. Vet Affairs Med Ctr, Denver, CO USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. Univ Alabama, Sch Med, Birmingham, AL USA. Vet Affairs Med Ctr, Birmingham, AL USA. Univ N Carolina, Chapel Hill, NC USA. Univ Miami, Miami, FL 33152 USA. Northwestern Univ, Chicago, IL 60611 USA. Indiana Univ, Indianapolis, IN 46204 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Adult AIDS Clin Trials Grp, Operat Ctr, Rockville, MD USA. Frontier Sci & Technol Res Fdn, Amherst, NY USA. NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. RP Kuritzkes, DR (reprint author), Univ Colorado, Hlth Sci Ctr, Div Infect Dis, 4200 E 9th Ave B-168, Denver, CO 80262 USA. OI Murphy, Robert/0000-0003-3936-2052 FU NIAID NIH HHS [AI-38855, AI-32770, AI-38858] NR 27 TC 41 Z9 41 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR 16 PY 1999 VL 13 IS 6 BP 685 EP 694 DI 10.1097/00002030-199904160-00009 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 195UT UT WOS:000080271100009 PM 10397563 ER PT J AU Fernandez, T Yan, WL Hamburger, S Rapoport, JL AF Fernandez, T Yan, WL Hamburger, S Rapoport, JL TI Apolipoprotein E alleles in childhood-onset schizophrenia SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Letter ID E EPSILON-2 ALLELE; ALZHEIMERS-DISEASE; E GENOTYPE; AGE; ASSOCIATION; FREQUENCY C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Joseph & Kathleen Bryan Alzheimers Dis Res Ctr, Dept Med, Durham, NC USA. NIMH, Sect Brain Aging & Dementia, Bethesda, MD 20892 USA. NIMH, Clin Neurosci Branch, Bethesda, MD 20892 USA. RP Fernandez, T (reprint author), NIMH, Child Psychiat Branch, Bldg 10,Room 3N202, Bethesda, MD 20892 USA. EM tomf@box-t.nih.gov RI Fernandez, Thomas/D-4295-2009 OI Fernandez, Thomas/0000-0003-0830-022X NR 29 TC 17 Z9 17 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 APR 16 PY 1999 VL 88 IS 2 BP 211 EP 213 DI 10.1002/(SICI)1096-8628(19990416)88:2<211::AID-AJMG20>3.0.CO;2-M PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 180KL UT WOS:000079384900020 PM 10206244 ER PT J AU McCracken, KA Bowen, WD de Costa, BR Matsumoto, RR AF McCracken, KA Bowen, WD de Costa, BR Matsumoto, RR TI Two novel sigma receptor ligands, BD1047 and LR172, attenuate cocaine-induced toxicity and locomotor activity SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE cocaine; toxicity; convulsion; psychomotor; locomotor; sigma receptor ID H-3 (+)-PENTAZOCINE; BINDING; RADIOLIGAND; ANTAGONISM; POTENT; RATS AB The ability of cocaine to interact with sigma receptors indicates that these sites may mediate the negative properties associated with cocaine use, such as toxicity and addiction. Previous studies have shown that the novel sigma receptor ligand, BD1008 (N-[2-(3,4-dicholophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine), effectively protects against cocaine-induced convulsions and locomotor activity in mice. Therefore, BD1047 ([2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(diamino)ethylamine) and LR172 (N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-homopiperidinyl)ethylamine), two analogs of BD1008, were tested to determine if they also have anti-cocaine properties. Receptor binding assays showed that BD1047 and LR172 both have high affinities for a receptors, but low to negligible affinities for dopamine, opioid, phencyclidine, and 5-HT2 sites. In behavioral studies, pretreatment of mice with BD1047 or LR172 reduced the convulsions, lethality, and locomotor activity produced by cocaine. The data indicates a possible role for a receptor ligands in the treatment of cocaine overdose and addiction. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Oklahoma, Hlth Sci Ctr, Coll Pharm, Dept Pharmacol & Toxicol, Oklahoma City, OK 73190 USA. NIDDKD, NIH, Med Chem Lab, Bethesda, MD 20892 USA. RP Matsumoto, RR (reprint author), Univ Oklahoma, Hlth Sci Ctr, Coll Pharm, Dept Pharmacol & Toxicol, POB 26901, Oklahoma City, OK 73190 USA. FU NIMH NIH HHS [MH50564] NR 25 TC 84 Z9 85 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 APR 16 PY 1999 VL 370 IS 3 BP 225 EP 232 DI 10.1016/S0014-2999(99)00113-2 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 190JX UT WOS:000079960400002 PM 10334496 ER PT J AU Parniak, MA Davis, M Kaufman, S Kempner, ES AF Parniak, MA Davis, M Kaufman, S Kempner, ES TI Radiation target analysis indicates that phenylalanine hydroxylase in rat liver extracts is a functional monomer SO FEBS LETTERS LA English DT Article DE phenylalanine hydroxylase; radiation inactivation; functional size ID INACTIVATION; FRAGMENTATION AB The minimal enzymatically functional form of purified rat hepatic phenylalanine hydroxylase (PAH) is a dimer of identical subunits, Radiation target analysis of PAH revealed that the minimal enzymatically active form in crude extracts corresponds to the monomer, The 'negative regulation' properties of the tetrahydrobiopterin cofactor in both crude and pure samples implicates a large multimeric structure, minimally a tetramer of PAH subunits, Preincubation of the samples with phenylalanine prior to irradiation abolished this inhibition component without affecting the minimal functional unit target sizes of the enzyme in both preparations. The characteristics of rat hepatic PAH determined by studies of the purified enzyme in vitro may not completely represent the properties of PAH in vivo. (C) 1999 Federation of European Biochemical Societies. C1 NIAMSD, NIH, Bethesda, MD 20892 USA. Sir Mortimer B Davis Jewish Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada. McGill Univ, Dept Med, Montreal, PQ H3T 1E2, Canada. NIMH, NIH, Bethesda, MD 20892 USA. RP Kempner, ES (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA. NR 17 TC 0 Z9 0 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 APR 16 PY 1999 VL 449 IS 1 BP 49 EP 52 DI 10.1016/S0014-5793(99)00392-0 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 189NF UT WOS:000079910900011 PM 10225426 ER PT J AU Jensen, MR Audolfsson, T Keek, CL Zimonjic, DB Thorgeirsson, SS AF Jensen, MR Audolfsson, T Keek, CL Zimonjic, DB Thorgeirsson, SS TI Gene structure and chromosomal localization of mouse cyclin G2 (Ccng2) SO GENE LA English DT Article DE cell cycle; gene expression; gene location; gene structure ID DNA-DAMAGE; CELL-CYCLE; DEPENDENT KINASES; G1 GENE; INHIBITION; HOMOLOGY; SEQUENCE; PROTEIN; ARREST; TARGET AB Cyclins are essential activators of cyclin-dependent kinases (Cdk) which, in turn, play pivotal roles in controlling transition through cell-cycle checkpoints. Cyclin G2 is a recently discovered second member of the G-type cyclins. The two members of the G-type cyclins, cyclin G1 and cyclin G2, share high structural similarity but their function remains to be defined. Here we characterize the structure of the mouse cyclin G2 gene by first cloning and sequencing the full-length mouse cyclin G2 cDNA. The cyclin G2 cDNA was used to isolate the cyclin G2 gene from a BAC library and to establish that the gene was transcribed from eight exons spanning a total of 8604 bp. The cyclin G2 gene was mapped by fluorescence in situ hybridization (FISH) to mouse chromosome 5E3.3.-F1.3. This region is syntenic to a region on human chromosome 4. The expression of cyclins G1 and G2 was examined in various tissues, but no correlation between expression patterns of the two genes was observed. However, during hepatic ontogenesis the cyclin G2 expression level decreased with age, whereas cyclin G1 expression increased. Transient expression of cyclin G2-green fluorescent protein (GFP) fusion protein in NIH3T3 cells showed that cyclin G2 is essentially a cytoplasmic protein, in contrast to the largely nuclear localization of cyclin G1. Our data suggest that, despite the close structural similarity between mouse cyclins G1 and G2, these proteins most likely perform distinct functions. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NCI, Expt Carcinogenesis Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RI Jensen, Michael/E-9677-2011 NR 30 TC 12 Z9 18 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD APR 16 PY 1999 VL 230 IS 2 BP 171 EP 180 DI 10.1016/S0378-1119(99)00057-8 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 190LA UT WOS:000079963300006 PM 10216255 ER PT J AU Kakuta, Y Sueyoshi, T Negishi, M Pedersen, LC AF Kakuta, Y Sueyoshi, T Negishi, M Pedersen, LC TI Crystal structure of the sulfotransferase domain of human heparan sulfate N-deacetylase/N-sulfotransferase 1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESTROGEN SULFOTRANSFERASE; REFINEMENT AB Heparan sulfate N-deacetylase/N-sulfotransferase (HSNST) catalyzes the first and obligatory step in the biosynthesis of heparan sulfates and heparin, The crystal structure of the sulfotransferase domain (NST1) of human HSNST-1 has been determined at 2.3-Angstrom resolution in a binary complex with 3'-phosphoadenosine 5'-phosphate (PAP), NST1 is approximately spherical with an open cleft, and consists of a single alpha/beta fold with a central five-stranded parallel beta-sheet and a three-stranded anti-parallel beta-sheet bearing an interstrand disulfide bond. The structural regions alpha 1, alpha 6, beta 1, beta 7, 5'-phosphosulfate binding loop (between beta 1 and alpha 1), and a random coil (between beta 8 and alpha 13) constitute the PAP binding site of NST1, The alpha 6 and random coil (between beta 2 and alpha 2), which form an open cleft near the 5'-phosphate of the PAP molecule, may provide interactions for substrate binding. The conserved residue Lys-614 is in position to form a hydrogen bond with the bridge oxygen of the 5'-phosphate. C1 NIEHS, Reprod & Dev Toxicol Lab, Pharmacogenet Sect, NIH, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), NIEHS, Reprod & Dev Toxicol Lab, Pharmacogenet Sect, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 23 TC 100 Z9 104 U1 1 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 16 PY 1999 VL 274 IS 16 BP 10673 EP 10676 DI 10.1074/jbc.274.16.10673 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 186VV UT WOS:000079751900002 PM 10196134 ER PT J AU Bahassi, EM O'Dea, MH Allali, N Messens, J Gellert, M Couturier, M AF Bahassi, EM O'Dea, MH Allali, N Messens, J Gellert, M Couturier, M TI Interactions of CcdB with DNA gyrase - Inactivation of GyrA, poisoning of the gyrase-DNA complex, and the antidote action of CcdA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI DNA; SEX FACTOR-F; BREAKAGE-REUNION DOMAIN; LETD CCDB; KILLER PROTEIN; PLASMID PROTEINS; SUBUNIT-A; CLEAVAGE; TRANSCRIPTION; REPLICATION AB The F plasmid-carried bacterial toxin, the CcdB protein, is known to act on DNA gyrase in two different ways. CcdB poisons the gyrase-DNA complex, blocking the passage of polymerases and leading to double-strand breakage of the DNA. Alternatively, in cells that overexpress CcdB, the A subunit of DNA gyrase (GyrA) has been found as an inactive complex with CcdB, We have reconstituted the inactive GyrA-CcdB complex by denaturation and renaturation of the purified GyrA dimer in the presence of CcdB, This inactivating interaction involves the N-terminal domain of GyrA, because similar inactive complexes were formed by denaturing and renaturing N-terminal fragments of the GyrA protein in the presence of CcdB, Single amino acid mutations, both in GyrA and in CcdB, that prevent CcdB-induced DNA cleavage also prevent formation of the inactive complexes, indicating that some essential interaction sites of GyrA and of CcdB are common to both the poisoning and the inactivation processes. Whereas the lethal effect of CcdB is most probably due to poisoning of the gyrase-DNA complex, the inactivation pathway may prevent cell death through formation of a toxin antitoxin-like complex between CcdB and newly translated GyrA subunits, Both poisoning and inactivation can be prevented and reversed in the presence of the F plasmid-encoded antidote, the CcdA protein. The products of treating the inactive GyrA-CcdB complex with CcdA are free GyrA and a CcdB-CcdA complex of approximately 44 kDa, which may correspond to a (CcdB),(CcdA), heterotetramer. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Free Univ Brussels, Dept Biol Mol, Lab Genet Procaryotes, B-1640 Rhode St Genese, Belgium. Free Univ Brussels VIB, B-1640 Rhode St Genese, Belgium. RP NIDDK, Mol Biol Lab, NIH, Bldg 5,Rm 241,5 Ctr Dr, Bethesda, MD 20892 USA. RI Messens, Joris/K-5856-2016 OI Messens, Joris/0000-0002-2128-8264 NR 49 TC 56 Z9 57 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 16 PY 1999 VL 274 IS 16 BP 10936 EP 10944 DI 10.1074/jbc.274.16.10936 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 186VV UT WOS:000079751900041 PM 10196173 ER PT J AU Bi, L Okabe, I Bernard, DJ Wynshaw-Boris, A Nussbaum, RL AF Bi, L Okabe, I Bernard, DJ Wynshaw-Boris, A Nussbaum, RL TI Proliferative defect and embryonic lethality in mice homozygous for a deletion in the p110 alpha subunit of phosphoinositide 3-kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE; REGULATORY SUBUNIT; P85-ALPHA GENE; INHIBITION; GROWTH; 3,4,5-TRISPHOSPHATE; WORTMANNIN; PATHWAYS; KINASES; CROSS AB Phosphatidylinositol 3,4,5-trisphosphate is a phospholipid signaling molecule involved in many cellular functions including growth factor receptor signaling, cytoskeletal organization, chemotaxis, apoptosis, and protein trafficking. Phosphorylation at the 3 position of the inositol ring is catalyzed by many different 3-kinases (classified as types I-A, I-B, II, and III), but the physiological roles played by each of the different 3-kinase isozymes during embryonic development and in homeostasis in animals is incompletely understood, Mammalian type I-A kinase isozymes are heterodimers that are active at 37 degrees C when the catalytic 110-kDa subunit interacts through an amino-terminal binding domain with a regulatory 85- or 55-kDa subunit, Using gene targeting in embryonic stem cells, we deleted this binding domain in the gene encoding the alpha isoform of the 110-kDa catalytic subunit (Pik3ca) of the alpha isozyme of the type I-A kinases, leading to loss of expression of the p110 catalytic subunit. We show that Pik3ca(del/del) embryos are developmentally delayed at embryonic day (E) 9.5 and die between E9.5 and E10.5. E9.5 Pik3ca(del/del) embryos have a profound proliferative defect but no increase in apoptosis, A proliferative defect is supported by the observation that fibroblasts from Pik3ca(del/del) embryos fail to replicate in Dulbecco's modified Eagle's medium and fetal calf serum, even with supplemental growth factors. C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Nussbaum, RL (reprint author), NHGRI, Genet Dis Res Branch, NIH, 49 Convent Dr MSC 4472, Bethesda, MD 20892 USA. NR 36 TC 290 Z9 298 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 16 PY 1999 VL 274 IS 16 BP 10963 EP 10968 DI 10.1074/jbc.274.16.10963 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 186VV UT WOS:000079751900044 PM 10196176 ER PT J AU Varnai, P Rother, KI Balla, T AF Varnai, P Rother, KI Balla, T TI Phosphatidylinositol 3-kinase-dependent membrane association of the Bruton's tyrosine kinase pleckstrin homology domain visualized in single living cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID X-LINKED AGAMMAGLOBULINEMIA; PH DOMAIN; SIGNAL-TRANSDUCTION; PLASMA-MEMBRANE; INOSITOL TRISPHOSPHATE; ACTIVATION; 3-KINASE; MUTATION; TRANSLOCATION; SPECIFICITY AB Phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P-3) has been proposed to act as a second messenger to recruit regulatory proteins to the plasma membrane via their pleckstrin homology (PH) domains. The PH domain of Bruton's tyrosine kinase (Btk), which is mutated in the human disease X-linked agammaglobulinemia, has been shown to interact with PI(3,4,5)P-3 in vitro. In this study, a fusion protein containing the PH domain of Btk and the enhanced green fluorescent protein (BtkPH-GFP) was constructed and utilized to study the ability of this PH domain to interact with membrane inositol phospholipids inside living cells. The localization of expressed BtkPH-GFP in quiescent NIH 3T3 cells was indistinguishable from that of GFP alone, both being cytosolic as assessed by confocal microscopy. In NIH 3T3 cells coexpressing BtkPH-GFP and the epidermal growth factor receptor, activation of epidermal growth factor or endogenous platelet-derived growth factor receptors caused a rapid (<3 min) translocation of the cytosolic fluorescence to ruffle-like membrane structures. This response was not observed in cells expressing GFP only and was completely inhibited by treatment with the PI 3-kinase inhibitors wortmannin and LY 292004, Membrane-targeted PI 3-kinase also caused membrane localization of BtkPH-GFP that was slowly reversed by wortmannin. When the R28C mutation of the Btk PH domain, which causes X-linked agammaglobulinemia, was introduced into the fluorescent construct, no translocation was observed after stimulation. Tn contrast, the E41K mutation, which confers transforming activity to native Btk, caused significant membrane localization of BtkPH-GFP with characteristics indicating its possible binding to PI(4,5)P-2. This mutant, but not wild-type BtkPH-GFP, interfered with agonist-induced PI(4,5)P-2 hydrolysis in COS-7 cells. These results show in intact cells that the PH domain of Btk binds selectively to 3-phosphorylated lipids after activation of PI 3-kinase enzymes and that losing such binding ability or specificity results in gross abnormalities in the function of the enzyme. Therefore, the interaction with PI(3,4,5)P-3 is likely to be an important determinant of the physiological regulation of Btk and can be utilized to visualize the dynamics and spatiotemporal organization of changes in this phospholipid in living cells. C1 NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Balla, T (reprint author), NICHD, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Rm 6A35,49 Convent Dr, Bethesda, MD 20892 USA. OI Balla, Tamas/0000-0002-9077-3335 NR 42 TC 207 Z9 214 U1 1 U2 6 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 APR 16 PY 1999 VL 274 IS 16 BP 10983 EP 10989 DI 10.1074/jbc.274.16.10983 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 186VV UT WOS:000079751900047 PM 10196179 ER PT J AU Nemes, Z Marekov, LN Steinert, PM AF Nemes, Z Marekov, LN Steinert, PM TI Involucrin cross-linking by transglutaminase 1 - Binding to membranes directs residue specificity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CORNIFIED CELL-ENVELOPE; PROLINE-RICH PROTEINS; LAMELLAR ICHTHYOSIS; KERATINOCYTE TRANSGLUTAMINASE; EPIDERMAL-KERATINOCYTES; TERMINAL DIFFERENTIATION; SUBSTRATE PROPERTIES; CALCIUM REGULATION; ENZYME; COMPONENTS AB The transglutaminase 1 (TGase 1) enzyme is essential for the assembly of the cell envelope barrier in stratified squamous epithelia, It is usually bound to membranes, but to date most studies with it have involved solution assays. Here we describe an in vitro model system for characterizing the function of TGase 1 on the surface of synthetic lipid vesicles (SLV) of composition similar to eukaryote plasma membranes. Recombinant baculovirus-expressed human TGase 1 readily binds to SLV and becomes active in cross-linking above 10 mu M Ca2+, in comparison to above 100 mu M in solution assays, suggesting that the membrane surface is important for enzyme function. Involucrin also binds to SLV containing 12-18% phosphatidylserine and at Ca2+ concentrations above 1 mu M. In reactions of involucrin with TGase 1 enzyme in solution, 80 of its 150 glutamines serve as donor residues. However, on SLV carrying both involucrin and TGase 1, only five glutamines serve as donors, of which glutamine 496 was the most favored, As controls, there was no change in specificity toward the glutamines of other substrates used by free or SLV-bound TGase 1 enzyme. We propose a model in which involucrin and TGase 1 bind to membranes shortly after expression in differentiating keratinocytes, but cross-linking begins only later as intracellular Ca2+ levels increase. Furthermore, the data suggest that the membrane surface regulates the steric interaction of TGase 1 with substrates such as involucrin to permit specific cross linking for initiation of cell envelope barrier formation. C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. RP Steinert, PM (reprint author), NIAMS, Skin Biol Lab, NIH, Bldg 6,Rm 425, Bethesda, MD 20892 USA. NR 59 TC 39 Z9 39 U1 0 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 APR 16 PY 1999 VL 274 IS 16 BP 11013 EP 11021 DI 10.1074/jbc.274.16.11013 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 186VV UT WOS:000079751900051 PM 10196183 ER PT J AU Goldsmith, PK Fan, GF Ray, K Shiloach, J McPhie, P Rogers, KV Spiegel, AM AF Goldsmith, PK Fan, GF Ray, K Shiloach, J McPhie, P Rogers, KV Spiegel, AM TI Expression, purification, and biochemical characterization of the amino-terminal extracellular domain of the human calcium receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PUTATIVE PHEROMONE RECEPTORS; HUMAN CA2+ RECEPTOR; SENSING RECEPTOR; CELL-SURFACE; CA2+-SENSING RECEPTOR; SIGNAL-TRANSDUCTION; GLUTAMATE RECEPTORS; CIRCULAR-DICHROISM; BINDING-PROTEINS; MULTIGENE FAMILY AB We purified the extracellular domain (ECD) of the human calcium receptor (hCaR) from the medium of HEK-293 cells stably transfected with a hCaR cDNA containing an isoleucine 599 nonsense mutation. A combination of lectin, anion exchange, and gel permeation chromatography yielded milligram quantities of >95% pure protein from 15 liters of starting culture medium. The purified ECD ran as an similar to 78-kDa protein on SDS-polyacrylamide gel electrophoresis and was found to be a disulfide-linked dimer. Its NH2-terminal sequence, carbohydrate content, and CD spectrum were defined. Tryptic proteolysis studies showed two major sites accessible to cleavage. These studies provide new insights into the structure of the hCaR ECD. Availability of purified ECD protein should permit further structural studies to help define the mechanism of Ca2+ activation of this G protein-coupled receptor. C1 NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Biotechnol Unit, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. NPS Pharmaceut, Salt Lake City, UT 84108 USA. RP Spiegel, AM (reprint author), NIDDK, Metab Dis Branch, NIH, 10-9N-222, Bethesda, MD 20892 USA. NR 25 TC 52 Z9 52 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 APR 16 PY 1999 VL 274 IS 16 BP 11303 EP 11309 DI 10.1074/jbc.274.16.11303 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 186VV UT WOS:000079751900088 PM 10196220 ER PT J AU Chandrasekaran, S Guo, NH Rodrigues, RG Kaiser, J Roberts, DD AF Chandrasekaran, S Guo, NH Rodrigues, RG Kaiser, J Roberts, DD TI Pro-adhesive and chemotactic activities of thrombospondin-1 for breast carcinoma cells are mediated by alpha(3)beta(1) integrin and regulated by insulin-like growth factor-1 and CD98 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EXTRACELLULAR-MATRIX PROTEINS; HEPARIN-BINDING DOMAIN; CANCER CELLS; I REPEATS; PLATELET THROMBOSPONDIN; ENDOTHELIAL-CELLS; MELANOMA-CELLS; TUMOR-GROWTH; RECEPTOR; ANGIOGENESIS AB Thrombospondin-1 (TSP1) is a matricellular protein that displays both pro- and anti-adhesive activities. Binding to sulfated glycoconjugates mediates most high affinity binding of soluble TSP1 to MDA-MB-435 cells, but attachment and spreading of these cells on immobilized TSP1 is primarily beta(1) integrin-dependent. The integrin alpha(3)beta(1) is the major mediator of breast carcinoma cell adhesion and chemotaxis to TSP1. This integrin is partially active in MDA-MB-435 cells but is mostly inactive in MDA-MB-231 and MCF-7 cells, which require beta(1) integrin activation to induce spreading on TSP1. Integrin-mediated cell spreading on TSP1 is accompanied by extension of filopodia containing beta(1) integrins. TSP1 binding activity of the alpha(3)beta(1) integrin is not stimulated by CD47-binding peptides from TSP1 or by protein kinase C activation, which activate alpha(v)beta(3) integrin function in the same cells. In MDA-MB-231 but not MDA-MB-435 cells, this integrin is activated by pertussis toxin, whereas serum, insulin, insulin-like growth factor-1, and ligation of CD98 increase activity of this integrin in both cell lines. Serum stimulation is accompanied by increased surface expression of CD98, whereas insulinlike growth factor-1 does not increase CD98 expression. Thus, the pro-adhesive activity of TSP1 for breast carcinoma cells is controlled by several signals that regulate activity of the alpha(3)beta(1) integrin. C1 NCI, Pathol Lab, 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 45 TC 90 Z9 91 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 APR 16 PY 1999 VL 274 IS 16 BP 11408 EP 11416 DI 10.1074/jbc.274.16.11408 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 186VV UT WOS:000079751900102 PM 10196234 ER PT J AU Aravind, L Koonin, EV AF Aravind, L Koonin, EV TI Gleaning non-trivial structural, functional and evolutionary information about proteins by iterative database searches SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE iterative database search; PSI-BLAST; structure prediction; DNA ligase; sialoglycoprotease ID MYCOPLASMA-GENITALIUM PROTEINS; V(D)J RECOMBINATION; ESCHERICHIA-COLI; DNA-LIGASE; PASTEURELLA-HAEMOLYTICA; CRYSTAL-STRUCTURE; GENE-EXPRESSION; PSI-BLAST; DOMAIN; SEQUENCES AB Using a number of diverse protein families as test cases, we investigate the ability of the recently developed iterative sequence database search method, PSI-BLAST, to identify subtle relationships between proteins that originally have been deemed detectable only at the level of structure-structure comparison. We show that PSI-BLAST can detect many, though not all, of such relationships, but the success critically depends on the optimal choice of the query sequence used to initiate the search. Generally, there is a correlation between the diversity of the sequences detected in the first pass of database screening and the ability of a given query to detect subtle relationships in subsequent iterations. Accordingly, a thorough analysis of protein superfamilies at the sequence level is necessary in order to maximize the chances of gleaning non-trivial structural and functional inferences, as opposed to a single search, initiated, for example, with the sequence of a protein whose structure is available. This strategy is illustrated by several findings, each of which involves an unexpected structural prediction: (i) a number of previously undetected proteins with the HSP70-actin fold are identified, including a highly conserved and nearly ubiquitous family of metal-dependent proteases (typified by bacterial O-sialoglycoprotease) that represent an adaptation of this fold to a new type of enzymatic activity; (ii) we show that, contrary to the previous conclusions, ATP-dependent and NAD-dependent DNA ligases are confidently predicted to possess the same fold; (iii) the C-terminal domain of S-phosphoglycerate dehydrogenase, which binds serine and is involved in allosteric regulation of the enzyme activity, is shown to typify a new superfamily of ligand-binding, regulatory domains found primarily in enzymes and regulators of amino acid and purine metabolism; (iv) the immunoglobulin-like DNA-binding domain previously identified in the structures of transcription factors NF kappa B and NFAT is shown to be a member of a distinct superfamily of intracellular and extracellular domains with the immunoglobulin fold; and (v) the Rag-2 subunit of the V-D-J recombinase is shown to contain a kelch-type beta-propeller domain which rules out its evolutionary relationship with bacterial transposases. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov NR 95 TC 306 Z9 312 U1 1 U2 5 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 APR 16 PY 1999 VL 287 IS 5 BP 1023 EP 1040 DI 10.1006/jmbi.1999.2653 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 187WV UT WOS:000079812000018 PM 10222208 ER PT J AU Gunatilaka, AAL Ramdayal, FD Sarragiotto, MH Kingston, DGI Sackett, DL Hamel, E AF Gunatilaka, AAL Ramdayal, FD Sarragiotto, MH Kingston, DGI Sackett, DL Hamel, E TI Synthesis and biological evaluation of novel paclitaxel (Taxol) D-ring modified analogues SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID TAXANES; CONFORMATIONS; DERIVATIVES; CHEMISTRY; BACCATIN; AGENT; NMR AB The semisynthesis and biological activity of paclitaxel (Taxol) analogues in which the oxygen atom in ring D is substituted by a sulfur or a selenium atom is presented. These derivatives were synthesized and tested in order to make more transparent the role of the oxetane ring in the biological activity of paclitaxel. The sulfur derivatives were found to be less active than paclitaxel in biological assays, while the selenium derivative could not be converted to its 4-acyl analogue. The results with the sulfur analogues suggest that the oxygen atom in the oxetane ring plays an important role in the mechanism by which paclitaxel exhibits its anticancer activity. C1 Virginia Polytech Inst & State Univ, Dept Chem, Blacksburg, VA 24061 USA. NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diag, Fred Hutchinson Canc Res Ctr, Frederick, MD 21702 USA. RP Kingston, DGI (reprint author), Virginia Polytech Inst & State Univ, Dept Chem, Blacksburg, VA 24061 USA. OI Kingston, David/0000-0001-8944-246X NR 30 TC 58 Z9 62 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD APR 16 PY 1999 VL 64 IS 8 BP 2694 EP 2703 DI 10.1021/jo982095h PG 10 WC Chemistry, Organic SC Chemistry GA 189VM UT WOS:000079926900017 ER PT J AU Basile, AS Brichta, AM Harris, BD Morse, D Coling, D Skolnick, P AF Basile, AS Brichta, AM Harris, BD Morse, D Coling, D Skolnick, P TI Dizocilpine attenuates streptomycin-induced vestibulotoxicity in rats SO NEUROSCIENCE LETTERS LA English DT Article DE rat; dizocilpine; streptomycin; vestibular organ; hair cells; behavior ID RECEPTOR; SPERMINE AB NMDA receptor mediated excitotoxicity contributes substantially to aminoglycoside antibiotic-induced cochlear damage. Since vestibular as well as cochlear hair cells have glutamatergic synapses, aminoglycoside-induced vestibulotoxicity may also have an excitotoxic component. This hypothesis was tested by examining the effects of the uncompetitive NMDA receptor antagonist dizocilpine on streptomycin-induced vestibulotoxicity. Streptomycin-treated rats exhibited almost complete destruction of sensory hair cells in the crista ampullaris, vestibular impairment in the drop test, and hyperkinesia. Concurrent treatment with dizocilpine not only rescued a substantial population of sensory hair cells in the cristae, but prevented the attendant hyperkinesis and vestibular impairments. These results indicate that excitotoxic mechanisms contribute to aminoglycoside-induced vestibulotoxicity and that NMDA antagonists may be useful in attenuating aminoglycoside ototoxicity. (C) 1999 Elsevier Science Ireland Ltd. Ail rights reserved. C1 NIDDK, Neurosci Grp, Lab Bioorgan Chem, NIH, Bethesda, MD 20892 USA. Univ Chicago, Sch Med, Dept Surg, Chicago, IL 60637 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Eli Lilly & Co, Neurosci Discovery, Indianapolis, IN 46285 USA. RP Basile, AS (reprint author), NIDDK, Neurosci Grp, Lab Bioorgan Chem, NIH, Bethesda, MD 20892 USA. OI Coling, Donald/0000-0001-6285-5336 NR 18 TC 23 Z9 23 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD APR 16 PY 1999 VL 265 IS 2 BP 71 EP 74 DI 10.1016/S0304-3940(99)00050-6 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 191JV UT WOS:000080020000001 PM 10327171 ER PT J AU Rosamond, W Broda, G Kawalec, E Rywik, S Pajak, A Cooper, L Chambless, L AF Rosamond, W Broda, G Kawalec, E Rywik, S Pajak, A Cooper, L Chambless, L TI Comparison of medical care and survival of hospitalized patients with acute myocardial infarction in Poland and the United states SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY HEART-DISEASE; CASE-FATALITY; MONICA PROJECT; MORTALITY; COUNTRIES; COMMUNITY; MINNESOTA; TRENDS AB Few studies have evaluated between-country differences in medical care and survival after acute myocardial infarction, and none have compared the US with countries from Eastern Europe, Comparable data from the US (Atherosclerosis Risk in Communities Study [US-ARIC]) and Poland (Multinational Monitoring of Trends and Determinants in Cardiovascular Disease project [Pol-MONICA]) were developed, From 1987 through 1993, a total of 3,694 patients were hospitalized with acute myocardial infarction events in the 2 Pol-MONICA communities and 4,801 in the 4 US-ARIC communities. Patients in the US-ARIC were 1.7 times more likely to be treated in a coronary care unit and received cardiac procedures, calcium channel blockers, and thrombolytic agents significantly more often than patients in the Pol-MONICA, The use of antiplatelet agents, nitrates, angiotensin-converting enzyme inhibitors, and beta blockade agents was similar in both countries. Case fatality (28-day) rates after hospitalized acute myocardial infarction were nearly identical (men, 7% in Pol-MONICA vs 6% in US-ARIC; women, 9% in Pol-MONICA vs 8% in US-ARIC), However, when fatal coronary heart disease events not associated with a hospitalized myocardial infarction were included, the US-ARIC rates were less than half than those seen in Pol-MONICA. Substantial differences in treatment of hospitalized acute myocardial infarction between countries did not translate into a survival advantage For patients reaching clinical attention, Differences in case severity, arising from the high out-of-hospital coronary death rate in Poland may play an important role in this finding. (C)1999 by Excerpta Medica, Inc. C1 Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. Stefan Cardinal Wyszynski Natl Inst Cardiol, Dept Cardiovasc Dis Epidemiol & Prevent, Warsaw, Poland. Jagiellonian Univ, Coll Med, Inst Publ Hlth, Krakow, Poland. NHLBI, Bethesda, MD 20892 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. RP Rosamond, W (reprint author), Univ N Carolina, Dept Epidemiol, McGavran Greenberg Hall,CB 7400, Chapel Hill, NC 27599 USA. EM wayne_rosamonde@unc.edu FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55018, N01-HC-55016] NR 26 TC 9 Z9 11 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 15 PY 1999 VL 83 IS 8 BP 1180 EP 1185 DI 10.1016/S0002-9149(99)00056-9 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 185GE UT WOS:000079659100007 PM 10215280 ER PT J AU Garcia-Closas, M Lubin, JH AF Garcia-Closas, M Lubin, JH TI Power and sample size calculations in case-control studies of gene-environment interactions: Comments on different approaches SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE case-control studies; epidemiologic methods; sample size; statistical power AB Power and sample size considerations are critical for the design of epidemiologic studies of gene-environment interactions. Hwang et at. (Am J Epidemiol 1994;140:1029-37) and Foppa and Spiegelman (Am J Epidemiol 1997;146:596-604) have presented power and sample size calculations for case-control studies of gene-environment interactions. Comparisons of calculations using these approaches and an approach for general multivariate regression models for the odds ratio previously published by Lubin and Call (Am J Epidemiol 1990;131:552-66) have revealed substantial differences under some scenarios. These differences are the result of a highly restrictive characterization of the null hypothesis in Hwang et al. and Foppa and Spiegelman, which results in an underestimation of sample size and overestimation of power for the test of a gene-environment interaction. A computer program to perform sample size and power calculations to detect additive or multiplicative models of gene-environment interactions using the Lubin and Call approach will be available free of charge in the near future from the National Cancer Institute. C1 NCI, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Garcia-Closas, M (reprint author), NCI, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 6130 Execut Blvd,EPN 443, Bethesda, MD 20892 USA. RI Garcia-Closas, Montserrat /F-3871-2015 OI Garcia-Closas, Montserrat /0000-0003-1033-2650 NR 9 TC 119 Z9 122 U1 0 U2 7 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 APR 15 PY 1999 VL 149 IS 8 BP 689 EP 692 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 185LY UT WOS:000079671500001 PM 10206617 ER PT J AU Bal, W Karantza, V Moudrianakis, EN Kasprzak, KS AF Bal, W Karantza, V Moudrianakis, EN Kasprzak, KS TI Interaction of nickel(II) with histones: In vitro binding of nickel(II) to the core histone tetramer SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE nickel(II); nickel(II)-thiol coordination; histone H3; histone H4; core histone tetramer; association constant; UV-vis spectroscopy; charge transfer band ID COMPLEXES; NUCLEOSOME; PROTEIN; H3; CH3CO-CYS-ALA-ILE-HIS-NH2; CARCINOGENESIS; RESOLUTION; STABILITY; SEQUENCE; PARTICLE AB The absorption spectra of Ni(II) bound to the core histone tetramer, (H3-H4)(2), of chicken erythrocytes in 500 mM NaCl + 100 mM phosphate (pH 7.4) were recorded. A charge transfer band was seen at 317 nm, characteristic of a bond between Ni(II) and the sulfur atom of Cys-110 of histone H3. The conditional affinity constants for Ni(II) binding at pH 7.4 for low and high Ni(II) saturation (log K-c = 4.26 +/- 0.02 and 5.26 +/- 0.11 M-1, respectively) were calculated from spectrophotometric titrations with the use of this band. The binding of Ni(II) to (H3-H4)(2) is proposed to involve the Cys-110 and His-113 of different H3 molecules within the tetramer, The competition between histones and low-molecular-weight chelators for NI(II) in the cell nucleus, histidine and glutathione, is discussed on the basis of the above results, indicating that histone H3 is very likely to bind Ni(II) dissolved intracellularly from phagocytosed particulate nickel compounds. (C) 1999 Academic Press. C1 NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. Univ Wroclaw, Fac Chem, PL-50138 Wroclaw, Poland. RP Kasprzak, KS (reprint author), NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Bldg 538,Room 205, Frederick, MD 21702 USA. NR 39 TC 31 Z9 32 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 APR 15 PY 1999 VL 364 IS 2 BP 161 EP 166 DI 10.1006/abbi.1999.1137 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 188GJ UT WOS:000079838200004 PM 10190970 ER PT J AU Castan, I Wijkander, J Manganiello, V Degerman, E AF Castan, I Wijkander, J Manganiello, V Degerman, E TI Mechanisms of inhibition of lipolysis by insulin, vanadate and peroxovanadate in rat adipocytes SO BIOCHEMICAL JOURNAL LA English DT Article DE diabetes; insulin receptor substrate-1; phosphodiesterase type 3B; phosphoinositide 3-kinase; cAMP-dependent protein kinase ID DEPENDENT PROTEIN-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; INSULINOMIMETIC AGENTS; GLUCOSE-TRANSPORT; DIABETES-MELLITUS; 3T3-L1 ADIPOCYTES; TYROSINE KINASE; GROWTH-FACTOR; RECEPTOR; PHOSPHORYLATION AB Vanadate and peroxovanadate (pV), potent inhibitors of tyrosine phosphatases, mimic several of the metabolic actions of insulin. Here we compare the mechanisms for the anti-lipolytic action of insulin, vanadate and pV in rat adipocytes. Vanadate (5 mM) and pV (0.01 mM) inhibited lipolysis induced by 0.01-1 mu M isoprenaline, vanadate being more and pV less efficient than insulin (1 nM). A loss of anti-lipolytic effect of pV was observed by increasing the concentration of isoprenaline and/or pV. pV induced tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 to a greater extent than insulin, whereas vanadate affected these components little if at all. In addition, only a higher concentration (0.1 mM) of pV induced the tyrosine phosphorylation of p85, the 85 kDa regulatory subunit of phosphoinositide 3-kinase (PI-3K). Vanadate activated PI-3K-independent (in the presence of 10 nM isoprenaline) and PI-3K-dependent (in the presence of 100 nM isoprenaline) anti-lipolytic pathways, both of which were found to be independent of phosphodiesterase type 3B (PDE3B). pV (0.01 mM), like insulin, activated PI-3K- and PDE3B-dependent pathways. However, the anti-lipolytic pathway of 0.1 mM pV did not seem to require insulin receptor substrate-1-associated PI-3K and was found to be partly independent of PDE3B. Vanadate and pV (only at 0.01 mM), like insulin? decreased the isoprenaline-induced activation of cAMP-dependent protein kinase. Overall, these results underline the complexity and the diversity in the mechanisms that regulate lipolysis. C1 Univ Lund, Dept Cell & Mol Biol, Sect Mol Signalling, S-22100 Lund, Sweden. NHLBI, Pulm Crit Care Med Branch, Sect Biochem Physiol, NIH, Bethesda, MD 20892 USA. RP Degerman, E (reprint author), Univ Lund, Dept Cell & Mol Biol, Sect Mol Signalling, POB 94, S-22100 Lund, Sweden. NR 37 TC 29 Z9 30 U1 1 U2 2 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD APR 15 PY 1999 VL 339 BP 281 EP 289 DI 10.1042/0264-6021:3390281 PN 2 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 189RB UT WOS:000079918400010 PM 10191258 ER PT J AU Olsen, V Cawley, NX Brandt, J Egel-Mitani, M Loh, YP AF Olsen, V Cawley, NX Brandt, J Egel-Mitani, M Loh, YP TI Identification and characterization of Saccharomyces cerevisiae yapsin 3, a new member of the yapsin family of aspartic proteases encoded by the YPS3 gene SO BIOCHEMICAL JOURNAL LA English DT Article DE glycosylphosphatidylinositol-anchors; GPI-anchors; proprotein processing; yeast proteinases ID OPIOMELANOCORTIN-CONVERTING ENZYME; PROCESSING ENZYMES; PLASMA-MEMBRANE; YEAST YAP3; CLEAVAGE; PROTEIN; PEPTIDE; PURIFICATION; EFFICIENCY; SECRETION AB A new aspartic protease from Saccharomyces cerevisiae, with a high degree of similarity with yapsin 1 and yapsin 2 and a specificity for basic residue cleavage sites of prohormones, has been cloned. This enzyme was named yapsin 3. Expression of a C-terminally truncated non-membrane anchored yapsin 3 in yeast yielded a heterogeneous protein between 135-200 kDa which, upon treatment with endoglycosidase H, migrated as a 60 kDa form. Amino-acid analysis of the N-terminus of expressed yapsin 3 revealed two different N-terminal residues, serine-48 and phenylalanine-54, which followed a dibasic and a monobasic residue respectively. Cleavage of several prohormones by nonanchored yapsin 3 revealed a specificity distinct from that of yapsin 1. C1 NICHHD, Dev Neurobiol Lab, Cellular Neurobiol Sect, NIH, Bethesda, MD 20892 USA. Novo Nordisk AS, Mol Biol, Insulin Res, DK-2880 Bagsvaerd, Denmark. RP Loh, YP (reprint author), NICHHD, Dev Neurobiol Lab, Cellular Neurobiol Sect, NIH, Bethesda, MD 20892 USA. EM ypl@codon.nih.gov NR 29 TC 27 Z9 31 U1 0 U2 1 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD APR 15 PY 1999 VL 339 BP 407 EP 411 DI 10.1042/0264-6021:3390407 PN 2 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 189RB UT WOS:000079918400025 PM 10191273 ER PT J AU Feng, Y Hodge, DR Palmieri, G Chase, DL Longo, DL Ferris, DK AF Feng, Y Hodge, DR Palmieri, G Chase, DL Longo, DL Ferris, DK TI Association of polo-like kinase with alpha-, beta- and gamma-tubulins in a stable complex SO BIOCHEMICAL JOURNAL LA English DT Article DE cell-cycle regulation; kinases; spindle formation ID PEPTIDYL-PROLYL ISOMERASE; XENOPUS EGG EXTRACTS; PROTEIN-KINASE; SACCHAROMYCES-CEREVISIAE; SERINE/THREONINE KINASE; DROSOPHILA POLO; GENE; PLK1; IDENTIFICATION; SPINDLE AB The polo-like kinase (Plk) family has been shown to have an important role in the regulation of the cell-division cycle, especially in organization of the spindle structure, in species from fungi to humans. Recent reports have demonstrated that in mammalian cells Plk is associated with components of the anaphase-promoting complex and a peptidyl-prolyl isomerase, Pin1. To characterize a putative Plk-containing complex, we fractionated mitotic cell lysates on a gel-filtration column. The Plk complex was eluted from the column at molecular sizes ranging from 669 to 2500 kDa in the presence of detergent and high concentrations of salt, Specific associations of Plk with alpha-, beta- and gamma-tubulins in both interphase and mitotic cells were shown by reciprocal immunoprecipitations and immunoblottings and were independent of the microtubule polymerization state, whereas binding assays in vitro indicated that Plk interacts with alpha- and beta-tubulins directly. In addition, mitotic Plk was able to phosphorylate associated tubulins in vitro. Finally, we show that the kinase domain of the Plk molecule is both required and sufficient for its binding to tubulins in vivo. The specific interaction between Plk and tubulins might provide a molecular basis for the physiological functions of Plk in regulating the cell cycle, particularly in establishing the normal bipolar spindle. C1 NCI, Frederick Canc Res & Dev Ctr, Biol Mechanisms Sect, Lab Leukocyte Biol, Frederick, MD 21702 USA. NIA, Baltimore, MD 21224 USA. NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. RP Ferris, DK (reprint author), NCI, Frederick Canc Res & Dev Ctr, Biol Mechanisms Sect, Lab Leukocyte Biol, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 37 TC 62 Z9 62 U1 0 U2 2 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD APR 15 PY 1999 VL 339 BP 435 EP 442 DI 10.1042/0264-6021:3390435 PN 2 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 189RB UT WOS:000079918400029 PM 10191277 ER PT J AU Goldman, D AF Goldman, D TI General and specific genetic vulnerability to substance abuse SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 4 BP 1S EP 2S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600006 ER PT J AU Negrao, AB Gold, PW Negro, PJ Glassman, A Musselman, DL AF Negrao, AB Gold, PW Negro, PJ Glassman, A Musselman, DL TI Long-term medical consequences of major depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. New York State Psychiat Inst, New York, NY 10032 USA. Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. RI Negrao, Andre Brooking/C-9526-2014 OI Negrao, Andre Brooking/0000-0002-8133-6723 NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 10 BP 3S EP 3S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600012 ER PT J AU Maj, M Weinberger, D AF Maj, M Weinberger, D TI Brain hemispheric asymmetry and susceptibility to psychoses SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Naples, Dept Psychiat, I-80138 Naples, Italy. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 11 BP 4S EP 4S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600013 ER PT J AU Gutkind, JS AF Gutkind, JS TI The information superhighway inside the cell: The role of map kinases SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009 NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 15 BP 5S EP 5S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600017 ER PT J AU Egan, MF Callicott, JH Goldberg, T Bertolino, A Bigelow, L Weinberger, DR AF Egan, MF Callicott, JH Goldberg, T Bertolino, A Bigelow, L Weinberger, DR TI Neurochemical and cognitive phenotypes for genetic studies of schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 20 BP 6S EP 7S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600022 ER PT J AU Hyman, SE AF Hyman, SE TI The molecular revolution - Implications for neuropsychiatry SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 17 BP 6S EP 6S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600019 ER PT J AU Nicolson, R Singaracharlu, S Lenane, M Giedd, JN Hamburger, SD Bedwell, J Fernandez, T Rapoport, JL AF Nicolson, R Singaracharlu, S Lenane, M Giedd, JN Hamburger, SD Bedwell, J Fernandez, T Rapoport, JL TI Premorbid impairments in childhood-onset schizophrenia: Association with risk factors SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Fernandez, Thomas/D-4295-2009; Nicolson, Robert/E-4797-2011; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Fernandez, Thomas/0000-0003-0830-022X; Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 36 BP 11S EP 12S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600038 ER PT J AU Bedwell, JS Keller, B Smith, AK Goldberg, TE Hamburger, S Kumra, S Rapoport, JL AF Bedwell, JS Keller, B Smith, AK Goldberg, TE Hamburger, S Kumra, S Rapoport, JL TI Childhood-onset schizophrenia: Why does post-psychotic IQ decline? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 39 BP 13S EP 13S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600041 ER PT J AU Philibert, RA Winfield, S Damschoder-Williams, P Martin, B Ginns, E AF Philibert, RA Winfield, S Damschoder-Williams, P Martin, B Ginns, E TI The structure and developmental expression patterns of the human OPA-containing gene, a QTL for mental cognition SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. NIMH, Clin Neurosci Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 47 BP 15S EP 15S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600049 ER PT J AU Elman, I Alder, CM Gastfriend, DR Pickar, D Breier, A AF Elman, I Alder, CM Gastfriend, DR Pickar, D Breier, A TI A positron emission tomography study of effects of acute glucose deprivation in patients with schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA. NIMH, Expt Therapeut Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 61 BP 20S EP 20S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600063 ER PT J AU Adler, CM Malhotra, AK Elman, I Pickar, D Carson, RE Breier, A AF Adler, CM Malhotra, AK Elman, I Pickar, D Carson, RE Breier, A TI Effects of NMDA receptor antagonism on striatal dopamine release in patients with schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Expt Therapeut Branch, Bethesda, MD 20892 USA. NIH, Positron Emiss Tomog Dept, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 72 BP 23S EP 23S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600074 ER PT J AU Holt, JL Van Horn, J Esposito, G Meyer-Lindenberg, A Egan, MF Weinberger, DR Berman, KF AF Holt, JL Van Horn, J Esposito, G Meyer-Lindenberg, A Egan, MF Weinberger, DR Berman, KF TI Exploring hypofrontality: Contributing neurophysiological variables SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, IRP, Clin Brain Disorders Branch, Unit Integrat Neuroimaging,NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 74 BP 24S EP 24S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600076 ER PT J AU Bachus, SE Hyde, TM Albert, VR Kowalski, LRZ Fibiger, HC Herman, MM Kleinman, JE AF Bachus, SE Hyde, TM Albert, VR Kowalski, LRZ Fibiger, HC Herman, MM Kleinman, JE TI GLYT1a mRNA in amygdala in psychiatric disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, IRP, NIH, Bethesda, MD 20892 USA. Lilly Corp, Indianapolis, IN 46285 USA. Allelix, S Plainfield, NJ 07080 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 127 BP 39S EP 40S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600127 ER PT J AU Beatty, PA Bachus, SE Hyde, TM Rubinstein, SL Egan, MF AF Beatty, PA Bachus, SE Hyde, TM Rubinstein, SL Egan, MF TI Entorhinal cortical preprosomatostatin mRNA in neuroleptic-treated rats SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, IRP, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 125 BP 39S EP 39S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600125 ER PT J AU Shen, CH Bachus, SE Hyde, TM Albert, VR Kowalski, LRZ Egan, MF AF Shen, CH Bachus, SE Hyde, TM Albert, VR Kowalski, LRZ Egan, MF TI GLYT 1a mRNA levels in prefrontal cortex of chronic neuroleptic-treated rats SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 126 BP 39S EP 39S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600126 ER PT J AU Zaka, M Hyde, TM Bachus, SE Bower, CM Egan, MF AF Zaka, M Hyde, TM Bachus, SE Bower, CM Egan, MF TI GABA(A) mediated neurotransmission in chronic neuroleptic treated rats SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, IRP, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 128 BP 40S EP 40S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600128 ER PT J AU Romanczyk, TB Weickert, CS Akil, M Hyde, TM Herman, MM Kleinman, JE AF Romanczyk, TB Weickert, CS Akil, M Hyde, TM Herman, MM Kleinman, JE TI TrkB receptor expression in prefrontal cortex of schizophrenic and control subjects SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, IRP, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 134 BP 41S EP 42S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600134 ER PT J AU Khaing, ZZ Molteni, R Valentine, MG Weinberger, DR Lipska, BK AF Khaing, ZZ Molteni, R Valentine, MG Weinberger, DR Lipska, BK TI Expression of markers of dopaminergic, glutamatergic and gabaergic function in rats with neonatal ventral hippocampal damage SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, IRP, NIH, Bethesda, MD 20892 USA. RI Lipska, Barbara/E-4569-2017 NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 136 BP 42S EP 42S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600136 ER PT J AU Collins, FS AF Collins, FS TI The human genome prosect and the future of psychiatric research and practice SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Natl Human Genome Res Inst, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 141 BP 44S EP 44S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600141 ER PT J AU Winterer, G Weinberger, DR AF Winterer, G Weinberger, DR TI Intermediate phenotyping & electrophysiological models - A new research strategy SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 146 BP 45S EP 45S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600146 ER PT J AU Henn, FA Bertolino, A Callicott, JH Braus, DF Ende, G AF Henn, FA Bertolino, A Callicott, JH Braus, DF Ende, G TI Can one create homogenous subgroups of schizophrenia through MR studies? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Cent Inst Mental Hlth, D-6800 Mannheim, Germany. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 150 BP 47S EP 47S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600150 ER PT J AU Smith, MJ Wassermann, EM AF Smith, MJ Wassermann, EM TI Neurosteroids, gonadal steroids, & cortical excitability SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 152 BP 47S EP 47S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600152 ER PT J AU Lipska, BK Weinberger, DR AF Lipska, BK Weinberger, DR TI Neonatal lesion as a model of schizophrenia to identify predisposing genes SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, IRP, NIH, Bethesda, MD 20892 USA. RI Lipska, Barbara/E-4569-2017 NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 156 BP 48S EP 49S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600156 ER PT J AU Sunderland, T Friz, J Khin, N Putnam, K Lalonde, F Pascu, A Small, C Greenwood, P Parasuraman, R AF Sunderland, T Friz, J Khin, N Putnam, K Lalonde, F Pascu, A Small, C Greenwood, P Parasuraman, R TI Biologic profile of people "at risk" for Alzheimer's Disease SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. Catholic Univ, Cognit Sci Lab, Washington, DC USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 157 BP 49S EP 49S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600157 ER PT J AU Zubenko, GS Winwood, E Jacobs, B Teply, I Stiffler, JS Hughes, HB Huff, FJ Sunderland, T Martinez, AJ AF Zubenko, GS Winwood, E Jacobs, B Teply, I Stiffler, JS Hughes, HB Huff, FJ Sunderland, T Martinez, AJ TI Prospective study of rise factors for Alzheimer's Disease: Results at 7.5 years SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Pathol Neuropathol, Pittsburgh, PA 15261 USA. Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA. NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 159 BP 49S EP 50S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600159 ER PT J AU Goldman, D Enoch, MA Rotondo, A Altemus, M Greenberg, BD Cassano, G Murphy, DL Kaye, WH AF Goldman, D Enoch, MA Rotondo, A Altemus, M Greenberg, BD Cassano, G Murphy, DL Kaye, WH TI The 5HT2A-1438G > A polymorphism in anorexia nervosa and obsessive compulsive disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 174 BP 55S EP 55S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600174 ER PT J AU Knowler, WC Hanson, RL AF Knowler, WC Hanson, RL TI Obesity and type 2 diabetes: Epidemiology and genetics in the Pima Indians SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIDDKD, Phoenix, AZ 85014 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 176 BP 55S EP 55S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600176 ER PT J AU Malhotra, AK Buchanan, RW Breier, A Kane, J Goldman, D AF Malhotra, AK Buchanan, RW Breier, A Kane, J Goldman, D TI Benefits and pitfalls of pharmacogenetic studies of clozapine response SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Hillside Hosp, Glen Oaks, NY 11004 USA. Maryland Psychiat Res Ctr, Catonsville, MD USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 178 BP 56S EP 56S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600178 ER PT J AU Sher, L Enoch, MA Mazzanti, CM Hardin, TA Greenberg, BD Murphy, DL Goldman, D Rosenthal, NE AF Sher, L Enoch, MA Mazzanti, CM Hardin, TA Greenberg, BD Murphy, DL Goldman, D Rosenthal, NE TI Association studies of seasonal affective disorder and seasonability SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Sect Biol Rhythms, Bethesda, MD 20892 USA. NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 183 BP 57S EP 58S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600183 ER PT J AU Meyer-Lindenberg, A Ziemann, U Hajak, G Cohen, L Berman, KF AF Meyer-Lindenberg, A Ziemann, U Hajak, G Cohen, L Berman, KF TI Cortical instability: A direct demonstration of nonlinear dynamics in the human brain SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, Unit Integrat Neuroimaging, Bethesda, MD 20892 USA. NINDS, Human Cort Physiol Unit, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 191 BP 60S EP 60S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600191 ER PT J AU Roca, CA Schmidt, PJ Greenberg, BD Murphy, DL Rubinow, DR AF Roca, CA Schmidt, PJ Greenberg, BD Murphy, DL Rubinow, DR TI Serotonin and the efficacy of estrogen in perimenopausal depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 245 BP 76S EP 76S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600245 ER PT J AU Brown, ES Suppes, T McElroy, S Kmetz, G Frye, M Denicoff, K Keck, P Nolen, W Kupka, R Altshuler, L Rochussen, J Haytef, J Leverich, G Post, R AF Brown, ES Suppes, T McElroy, S Kmetz, G Frye, M Denicoff, K Keck, P Nolen, W Kupka, R Altshuler, L Rochussen, J Haytef, J Leverich, G Post, R TI A pilot trial of adjunctive topiramate in the treatment of bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. NIMH, Bethesda, MD USA. HC Rumke Grp, Stanley Fdn, Bipolar Treatment Outcome Network, Utrecht, Netherlands. Univ Calif Los Angeles, Ambulatory Clin Res Ctr, Los Angeles, CA 90024 USA. RI Nolen, Willem/E-9006-2014 NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 252 BP 78S EP 78S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600252 ER PT J AU Nahas, Z Speer, AM Molloy, M Oliver, NC Arana, GW Ballenger, JC Risch, SC George, MS AF Nahas, Z Speer, AM Molloy, M Oliver, NC Arana, GW Ballenger, JC Risch, SC George, MS TI Role of stimulation frequency in the antidepressant effect of left prefrontal rTMS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. NIMH, Dept Psychiat, Bethesda, MD 20892 USA. NIMH, Dept Radiol, Bethesda, MD 20892 USA. NIMH, Dept Neurol, Bethesda, MD 20892 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Ralph H Johnson Vet Affairs Hosp, Charleston, SC USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 256 BP 79S EP 80S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600256 ER PT J AU Iwata, N Cowley, DS Radel, M Floyd, L Ricker, B Ozaki, N Roy-Byrne, PP Goldman, D AF Iwata, N Cowley, DS Radel, M Floyd, L Ricker, B Ozaki, N Roy-Byrne, PP Goldman, D TI GABA(A) alpha 6 polymorphisms and relationship to benzodiazepine sensitivity SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIAAA, DICBR, Neurogenet Lab, Bethesda, MD USA. Fujita Hlth Univ, Sch Med, Dept Psychiat, Toyoake, Aichi 47011, Japan. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. NR 0 TC 1 Z9 1 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 265 BP 82S EP 82S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600264 ER PT J AU Fernandez, T Lewczyk, CM Castellanos, FX Simonis, T Jacobsen, LK Rapoport, JL AF Fernandez, T Lewczyk, CM Castellanos, FX Simonis, T Jacobsen, LK Rapoport, JL TI HLA alleles in attention-deficit hyperactivity disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NIH, Ctr Clin, HLA Lab, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Psychiat, W Haven, CT 06516 USA. RI Fernandez, Thomas/D-4295-2009 OI Fernandez, Thomas/0000-0003-0830-022X NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 271 BP 84S EP 84S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600270 ER PT J AU Lewczyk, CM Fernandez, T Castellanos, FX Koprivica, V Kashani, A Tayebi, N Ginns, EI Rapoport, JL Sidransky, E AF Lewczyk, CM Fernandez, T Castellanos, FX Koprivica, V Kashani, A Tayebi, N Ginns, EI Rapoport, JL Sidransky, E TI Lack of an association between dopamine transporter (DAT1) and ADHD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Clin Neurosci Branch, Bethesda, MD 20892 USA. RI Fernandez, Thomas/D-4295-2009 OI Fernandez, Thomas/0000-0003-0830-022X NR 0 TC 1 Z9 1 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 272 BP 84S EP 84S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600271 ER PT J AU Daly, RC Su, TP Schmidt, PJ Pickar, D Rubinow, DR AF Daly, RC Su, TP Schmidt, PJ Pickar, D Rubinow, DR TI CSF and behavioral changes after androgenic-anabolic steroid administration SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. Cheng Hsin Gen Hosp, Dept Psychiat, Taipei 112, Taiwan. NIMH, Expt Therapeut Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 291 BP 89S EP 89S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600290 ER PT J AU Williams, WA Shoaf, SE Hommer, D Rawlings, R George, DT AF Williams, WA Shoaf, SE Hommer, D Rawlings, R George, DT TI Changes in CSF indoleamines with acute plasma tryptophan depletion in humans SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIAAA, DICBR, Clin Studies Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 305 BP 93S EP 93S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600304 ER PT J AU Umhau, JC Diaz, R Graham, SE Rawlings, RR George, DT AF Umhau, JC Diaz, R Graham, SE Rawlings, RR George, DT TI Plasma glucose is related to cerebrospinal fluid neurotransmitters SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIAAA, Clin Studies Lab, Bethesda, MD 20892 USA. Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 306 BP 94S EP 94S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600305 ER PT J AU Winterer, G Coppola, R Egan, M Raedler, T Weinberger, D AF Winterer, G Coppola, R Egan, M Raedler, T Weinberger, D TI Genetics in schizophrenia: Electrophysiology of frontal vs temporal lobe dysfunction SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorder Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 307 BP 94S EP 94S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600306 ER PT J AU Goldberg, TE Sharma, T Egan, MF Seidman, LJ AF Goldberg, TE Sharma, T Egan, MF Seidman, LJ TI Intermediate phenotypes in families with schizophrenic members SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders, Bethesda, MD 20892 USA. Inst Psychiat, London SE5 8AF, England. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 322 BP 100S EP 100S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600321 ER PT J AU Haxby, JV AF Haxby, JV TI Human neural systems for face perception SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Sect Funct Brain Imaging, LBC, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 330 BP 102S EP 102S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600329 ER PT J AU Wyatt, RJ Henter, I Mojtabai, R Susser, E AF Wyatt, RJ Henter, I Mojtabai, R Susser, E TI Premorbid findings from the national Collaborative Study of Early Psychosis and Suicide (NCSEPS) SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Neuropsychiat Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 332 BP 103S EP 103S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600331 ER PT J AU Bertolino, A Callicott, JH Mattay, VS Weinberger, DR AF Bertolino, A Callicott, JH Mattay, VS Weinberger, DR TI Single-voxel and imaging with 1H-MRS in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 338 BP 105S EP 105S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600337 ER PT J AU Adler, CM Elman, I Weisenfeld, N Kesstler, L Pickar, D Breier, A AF Adler, CM Elman, I Weisenfeld, N Kesstler, L Pickar, D Breier, A TI Effects of 2-deoxyglucose-induced glucoprivation on striatal dopamine release in healthy volunteers SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Expt Therapeut Branch, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 349 BP 108S EP 108S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600348 ER PT J AU Zalla, T Koechlin, E Pietrini, P Basso, G Aquino, P Grafman, J AF Zalla, T Koechlin, E Pietrini, P Basso, G Aquino, P Grafman, J TI Distinct left and right amygdala activation in winning and losing situations SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. Inst Cognit Sci, F-69675 Bron, France. Univ Pisa, Dept Human & Environm Sci, Pisa, Italy. RI Basso, Gianpaolo/A-9208-2012 OI Basso, Gianpaolo/0000-0002-6245-9402 NR 0 TC 1 Z9 1 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 359 BP 111S EP 112S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600358 ER PT J AU Giovacchini, G Alexander, GE Furey, ML Horwitz, B Ricciardi, E Solaini, G Guazzelli, M Rapoport, SI Schapiro, MB Pietrini, P AF Giovacchini, G Alexander, GE Furey, ML Horwitz, B Ricciardi, E Solaini, G Guazzelli, M Rapoport, SI Schapiro, MB Pietrini, P TI Audiovisual stimulation (AS) reveals brain metabolic decline in healthy aging SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Scuola Super Sant Anna, Post Degree Studies, Pisa, 20892, Italy. NIA, Neurosci Lab, NIH, Bethesda, MD USA. Univ Pisa, Inst Psychiat, Pisa, Italy. Univ Pisa, Dept Human & Environm Sci, Pisa, Italy. RI Furey, Maura/H-5273-2013 NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 360 BP 112S EP 112S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600359 ER PT J AU Castellanos, FX Giedd, JN Sharp, WS Walter, JM Lewczyk, CM Rapoport, JL AF Castellanos, FX Giedd, JN Sharp, WS Walter, JM Lewczyk, CM Rapoport, JL TI Anatomic brain MRI in girls with Attention-Deficit/Hyperactivity Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 369 BP 115S EP 115S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600368 ER PT J AU Giedd, JN Castellanos, FX Blumenthal, J Rapoport, JL AF Giedd, JN Castellanos, FX Blumenthal, J Rapoport, JL TI Sexual dimorphism of human brain development: Ages 3 to 18 SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Child Psychiat Branch, Bethesda, MD 20902 USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 1 Z9 1 U1 0 U2 2 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 370 BP 115S EP 115S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600369 ER PT J AU Swedo, SE Lougee, LC Garvey, MA Hamilton, CS Slattery, MJ AF Swedo, SE Lougee, LC Garvey, MA Hamilton, CS Slattery, MJ TI PANDAS: Is it the result of genetics and environment? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Pediat & Dev Neuropsychiat Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 394 BP 122S EP 122S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600393 ER PT J AU Gerton, BK Meyer-Lindenberg, A Holt, JL Weinberger, DR Berman, KF AF Gerton, BK Meyer-Lindenberg, A Holt, JL Weinberger, DR Berman, KF TI Neurophysiological correlates of the forward and backward digit span tasks as revealed by PET: Evidence for shared and distinct components SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, Unit Integrat Neuroimaging, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 418 BP 129S EP 129S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600417 ER PT J AU Osuch, EA Ketter, TA Kimbrell, TA George, MS Benson, BE Willis, MW McCann, U Post, RM AF Osuch, EA Ketter, TA Kimbrell, TA George, MS Benson, BE Willis, MW McCann, U Post, RM TI Regional cerebral metabolism unique to anxiety symptoms in affective disorder patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. VA Med Ctr, N Little Rock, AR 72114 USA. Med Univ S Carolina, Charlotte, NC USA. NR 0 TC 1 Z9 1 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 417 BP 129S EP 129S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600416 ER PT J AU Dunn, RT Willis, M Kimbrell, TA Speer, AM Osuch, EA Benson, B Repella, J Post, RM AF Dunn, RT Willis, M Kimbrell, TA Speer, AM Osuch, EA Benson, B Repella, J Post, RM TI Comparison of cerebral metabolism & blood flow in affective disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. VA Med Ctr, N Little Rock, AR 72114 USA. NR 0 TC 2 Z9 2 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 420 BP 130S EP 130S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600419 ER PT J AU Speer, AM Kimbrell, TA Wassermann, EM Willis, MW Post, RM AF Speer, AM Kimbrell, TA Wassermann, EM Willis, MW Post, RM TI 20 Hz and 1 Hz rTMS for 2 weeks differentially affects absolute rCBF in depressed patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. VA Med Ctr, N Little Rock, AR 72114 USA. NINDS, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 421 BP 130S EP 130S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600420 ER PT J AU Tenebank, CC Nahas, N Speer, AM Molloy, LM Stallings, LE Vincent, DJ Bohning, DE Spicer, KM Cheng, KT Risch, SC George, MS AF Tenebank, CC Nahas, N Speer, AM Molloy, LM Stallings, LE Vincent, DJ Bohning, DE Spicer, KM Cheng, KT Risch, SC George, MS TI Paralimbic activity declines with depression severity and improves with TMS response SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. NIMH, Dept Psychiat, Bethesda, MD 20892 USA. NIMH, Dept Radiol, Bethesda, MD 20892 USA. NIMH, Dept Neurol, Bethesda, MD 20892 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Ralph H Johnson Vet Affairs Hosp, Charleston, SC USA. NR 0 TC 1 Z9 1 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 428 BP 132S EP 132S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600427 ER PT J AU Bone, AD Callicott, JH Bertolino, A Mattay, VS Coppola, R Goldberg, TE Egan, MF Duyn, J Frank, JA Weinberger, DR AF Bone, AD Callicott, JH Bertolino, A Mattay, VS Coppola, R Goldberg, TE Egan, MF Duyn, J Frank, JA Weinberger, DR TI Limited working memory capacity in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, IRP, Clin Brain Disorders Branch, Washington, DC 20032 USA. NIH, OIR, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. RI Duyn, Jozef/F-2483-2010 NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 433 BP 134S EP 134S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600432 ER PT J AU Rakow, RL Bertolino, A Callicott, JH Mattay, VS Frank, JA Weinberger, DR AF Rakow, RL Bertolino, A Callicott, JH Mattay, VS Frank, JA Weinberger, DR TI N-acetylaspartate reduction in dorsolateral prefrontal cortex of patients with schizophrenia as revealed by short echo time 1H-MRS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20814 USA. NIH, Ctr Clin, Lab Diagnost Radiol Res, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 434 BP 134S EP 134S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600433 ER PT J AU Weidenhammer, KM Bertolino, A Callicott, JH Elman, I Mattay, VS Breier, A Frank, JA Pickar, D Weinberger, DR AF Weidenhammer, KM Bertolino, A Callicott, JH Elman, I Mattay, VS Breier, A Frank, JA Pickar, D Weinberger, DR TI The effects of neuroleptic treatment on H-1-MRSI measures in patients with schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NIMH, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. NIH, OD, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 435 BP 134S EP 135S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600434 ER PT J AU Bertolino, A Frye, M Callicott, JH Mattay, VS Post, R Weinberger, DR AF Bertolino, A Frye, M Callicott, JH Mattay, VS Post, R Weinberger, DR TI Neuronal pathology in the hippocampal area of patients with bipolar disorder: A H-1-MRSI study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1999 VL 45 IS 8 SU S MA 437 BP 135S EP 135S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600436 ER PT J AU Blumenthal, G Mattay, VS Callicott, JH Bertolino, A Das, S Heaton, I Langheim, F Duyn, J Frank, JA Weinberger, DR AF Blumenthal, G Mattay, VS Callicott, JH Bertolino, A Das, S Heaton, I Langheim, F Duyn, J Frank, JA Weinberger, DR TI Task-related activation of ipsilateral primary sensorimotor cortex: A bold fMRI study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, IRP, Washington, DC 20032 USA. OIR, Lab Diagnost Radiol Res, NIH, Bethesda, MD USA. RI Duyn, Jozef/F-2483-2010 NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 438 BP 135S EP 136S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600437 ER PT J AU Roffman, JL Bertolino, A Lipska, BK Van Gelderen, P Olson, AW Weinberger, DR AF Roffman, JL Bertolino, A Lipska, BK Van Gelderen, P Olson, AW Weinberger, DR TI Reduced NAA levels in the rat prefrontal cortex after neonatal hippocampal lesions: An in vivo H-1-MRS study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20814 USA. HHMI, Res Sholars Program, NIH, Bethesda, MD 20814 USA. NCRR, In Vivo NMR Ctr, NIH, Bethesda, MD 20814 USA. RI Lipska, Barbara/E-4569-2017 NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 436 BP 135S EP 135S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600435 ER PT J AU Bloch, M Cizza, G Lotsikas, A Schmidt, PJ Chrousos, GP Rubinow, DR AF Bloch, M Cizza, G Lotsikas, A Schmidt, PJ Chrousos, GP Rubinow, DR TI Cortisol response to oCRH in a model of pregnancy and parturition SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Rambam Med Ctr, Haifa, Israel. NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 443 BP 137S EP 137S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600442 ER PT J AU Usiskin, S Nicolson, R Krasnewich, D Wudarsky, M Lenane, M Rapoport, JL AF Usiskin, S Nicolson, R Krasnewich, D Wudarsky, M Lenane, M Rapoport, JL TI Velocardiofacial syndrome in childhood-onset schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Bethesda, MD 20892 USA. RI Nicolson, Robert/E-4797-2011 NR 0 TC 1 Z9 1 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 461 BP 143S EP 143S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600460 ER PT J AU Nicolson, R Swedo, SE Lenane, M Bedwell, J Rapoport, JL AF Nicolson, R Swedo, SE Lenane, M Bedwell, J Rapoport, JL TI Plasmapheresis treatment of childhood-onset obsessive-compulsive disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Pediat & Dev Neuropsychiat Branch, Bethesda, MD 20892 USA. RI Nicolson, Robert/E-4797-2011 NR 0 TC 0 Z9 0 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 APR 15 PY 1999 VL 45 IS 8 SU S MA 467 BP 144S EP 145S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600466 ER PT J AU Frye, MA Dunn, RT Gary, KA Kimbrell, TA Callahan, AM Luckenbaugh, DA Cora-Locatelli, G Vanderham, E Winokur, A Post, RM AF Frye, MA Dunn, RT Gary, KA Kimbrell, TA Callahan, AM Luckenbaugh, DA Cora-Locatelli, G Vanderham, E Winokur, A Post, RM TI Lack of correlation between cerebrospinal fluid thyrotropin-releasing hormone (TRH) and TRH-stimulated thyroid-stimulating hormone in patients with depression SO BIOLOGICAL PSYCHIATRY LA English DT Article DE thyrotropin-releasing hormone; thyroid-stimulating hormone; depression; cerebrospinal fluid ID ENDOGENOUS-DEPRESSION; CSF TRH AB Background: It has been proposed that elevated central thyrotropin-releasing hormone (TRH) is associated with the blunted thyroid-stimulating hormone (TSH) response to TRH in patients with depression. Few studies have directly evaluated this relationship between central nervous system and peripheral endocrine systems in the same patient population. Methods: 15 depressed patients (4 male, II female, 12 bipolar, and 3,unipolar) during a double-blind, medication-free period of at least 2 weeks duration, underwent a baseline lumbar puncture followed by a TRH stimulation rest. Cerebrospinal fluid (CSF) TRH and serial serum TSH,free thyroxine, triiodothyronine, prolactin, and cortisol were measured. A blunted response to TRH was defined as a delta TSH less than 7 mu U/mL. Results: There was no significant difference in mean CSF TRH between "blunters" (2.82 +/- 1.36 pg/mL) and "nonblunters" (3.97 +/- 0.62 pg/mL, p = .40). There was no evidence of an inverse relationship between CSF TRH and baseline or delta TSH. There was no correlation between CSF TRH and the severity of depression or any other endocrine measure. Conclusions: These darn are not consistent with the prediction of hypothalamic TRH hypersecretion and subsequent pituitary down-regulation in depression; however, CSF TRH may be from a nonparaventricular nucleus-hypothalamic source (i.e., limbic area, suprachiasmatic nucleus, brain stem-dorsal raphe) and thus, not necessarily related to peripheral neuroendocrine indices. (C) 1999 Society of Biological Psychiatry. C1 NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Univ Connecticut, Ctr Hlth, Farmington, CT USA. Brown Univ, Sch Med, VA Med Ctr, Providence, RI 02912 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, Bldg 10,Room 3N-212, Bethesda, MD 20892 USA. NR 20 TC 12 Z9 12 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 APR 15 PY 1999 VL 45 IS 8 BP 1049 EP 1052 DI 10.1016/S0006-3223(98)00322-9 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189FA UT WOS:000079892700015 PM 10386189 ER PT J AU Teruya-Feldstein, J Jaffe, ES Burd, PR Kingma, DW Setsuda, JE Tosato, G AF Teruya-Feldstein, J Jaffe, ES Burd, PR Kingma, DW Setsuda, JE Tosato, G TI Differential chemokine expression in tissues involved by Hodgkin's disease: Direct correlation of eotaxin expression and tissue eosinophilia SO BLOOD LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Hematology CY DEC 05-09, 1997 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol ID NF-KAPPA-B; INTERFERON-INDUCIBLE PROTEIN-10; TUMOR-NECROSIS-FACTOR; IN-VIVO; FUNCTIONAL-CHARACTERIZATION; RECEPTOR CCR3; T-LYMPHOCYTES; MESSENGER-RNA; CELLS; CHEMOATTRACTANT AB Hodgkin's disease (HD) is a lymphoid malignancy characterized by infrequent malignant cells surrounded by abundant inflammatory cells. In this study, we examined the potential contribution of chemokines to inflammatory cell recruitment in different subtypes of HD. Chemokines are small proteins that are active as chemoattractants and regulators of cell activation. We found that HD tissues generally express higher levels of interferon-gamma-inducible protein-10 (IP-10), Mig. RANTES, macrophage inflammatory protein-1 alpha (MIP-1 alpha). and eotaxin, but not macrophage-derived chemotactic factor (MDC), than tissues from lymphoid hyperplasia (LH). Within HD subtypes, expression of IP-10 and Mig was highest in the mixed cellularity (MC) subtype, whereas expression of eotaxin and MDC was highest in the nodular sclerosis (NS) subtype. A significant direct correlation was detected between evidence of Epstein-Barr virus (EBV) infection in the neoplastic cells and levels of expression of IP-10, RANTES, and MIP-1 alpha. Levels of eotaxin expression correlated directly with the extent of tissue eosinophilia. By immunohistochemistry, IP-10, Mig, and eotaxin proteins localized in the malignant Reed-Sternberg (RS) cells and their variants, and to some surrounding inflammatory cells. Eotaxin was also detected in fibroblasts and smooth muscle cells of vessels. These results provide evidence of high level chemokine expression in HD tissues and suggest that chemokines may play an important role in the recruitment of inflammatory cell infiltrates into tissues involved by HD. (C) 1999 by The American Society of Hematology. C1 NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Teruya-Feldstein, J (reprint author), NCI, Hematopathol Sect, Pathol Lab, NIH, Bldg 10,Room 2A33,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. NR 47 TC 96 Z9 99 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 1999 VL 93 IS 8 BP 2463 EP 2470 PG 8 WC Hematology SC Hematology GA 184YY UT WOS:000079642400004 PM 10194423 ER PT J AU Chan, CC Shen, DF Whitcup, SM Nussenblatt, RB LeHoang, P Roberge, FG Cassoux, N Herbort, C Zhuang, ZP AF Chan, CC Shen, DF Whitcup, SM Nussenblatt, RB LeHoang, P Roberge, FG Cassoux, N Herbort, C Zhuang, ZP TI Detection of human herpesvirus-8 and Epstein-Barr virus DNA in primary intraocular lymphomas SO BLOOD LA English DT Letter ID NERVOUS-SYSTEM LYMPHOMA; HUMAN-HERPESVIRUS-8; PATHWAY; AIDS C1 NEI, NIH, Bethesda, MD 20892 USA. Hop La Pitie Salpetriere, Dept Ophthalmol, Paris, France. Dept Ophthalmol, Lausanne, Switzerland. NCI, NIH, Bethesda, MD 20892 USA. RP Chan, CC (reprint author), NEI, NIH, Bethesda, MD 20892 USA. NR 10 TC 13 Z9 14 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 1999 VL 93 IS 8 BP 2749 EP 2751 PG 3 WC Hematology SC Hematology GA 184YY UT WOS:000079642400038 PM 10232895 ER PT J AU Troisi, RJ Freedman, AN Devesa, SS AF Troisi, RJ Freedman, AN Devesa, SS TI Incidence of colorectal carcinoma in the US - An update of trends by gender, race, age, subsite, and stage, 1975-1994 SO CANCER LA English DT Article DE colon carcinoma; rectal carcinoma; incidence; race; subsite; disease stage ID CANCER INCIDENCE; DIABETES-MELLITUS; UNITED-STATES; MORTALITY TRENDS AB BACKGROUND. Colon carcinoma incidence rates have risen sharply over the second half of this century, particularly among males and blacks. In the late 1970s, incidence rates among whites began to decline for distant disease. Approximately 10 years later regional disease rates began to fall. The decline in incidence rates among whites largely has been attributed to more widespread colorectal carcinoma screening. However, similar trends by stage in blacks have not been observed. METHODS. The incidence of colorectal carcinoma was evaluated by race, gender, age, and stage of disease for each subsite using data from > 220,000 cases diagnosed between 1975 and 1994 in the U. S. Surveillance, Epidemiology, and End Results program. RESULTS. Recent data have continued to show a decrease in incidence rates of total colorectal carcinoma in whites since the mid-1980s, particularly for the distal colon and rectum. Overall, proximal colon carcinoma rates were higher than distal colon or rectal carcinoma rates throughout the study period. Proximal colon carcinoma rates in blacks were considerably higher than in whites and continued to increase, whereas rates in whites showed signs of declining. The age-specific and stage-specific bends for proximal colon carcinoma in blacks were not consistent with the possibility of earlier disease detection through screening. CONCLUSIONS. Etiologic studies are necessary to understand the large increases in the incidence of proximal colon carcinoma among blacks. (C) 1999 American Cancer Society. C1 NCI, Div Canc Epidemiol & Genet, Biostat Branch, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Appl Res Branch, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Environm Epidemiol Branch, Bethesda, MD 20892 USA. RP Devesa, SS (reprint author), NCI, Div Canc Epidemiol & Genet, Biostat Branch, Execut Plaza S,Room 8048,6120 Execut Blvd, Bethesda, MD 20892 USA. NR 20 TC 122 Z9 129 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 0008-543X J9 CANCER JI Cancer PD APR 15 PY 1999 VL 85 IS 8 BP 1670 EP 1676 DI 10.1002/(SICI)1097-0142(19990415)85:8<1670::AID-CNCR5>3.0.CO;2-M PG 7 WC Oncology SC Oncology GA 184WF UT WOS:000079636200005 PM 10223559 ER PT J AU Bocchinfuso, WP Hively, WP Couse, JF Varmus, HE Korach, KS AF Bocchinfuso, WP Hively, WP Couse, JF Varmus, HE Korach, KS TI A mouse mammary tumor virus Wnt-1 transgene induces mammary gland hyperplasia and tumorigenesis in mice lacking estrogen receptor-alpha SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER CELLS; GROWTH-FACTOR; BETA-CATENIN; TRANSCRIPTIONAL ACTIVATION; TARGETED DISRUPTION; KINASE PATHWAY; PROTEIN-KINASE; ER-BETA; GENE; EXPRESSION AB Estrogens have important functions in mammary gland development and carcinogenesis. To better define these roles, we have used two previously characterized lines of genetically altered mice: estrogen receptor-or (ER alpha) knockout (ERKO) mice, which Lack the gene encoding ERa, and mouse mammary virus tumor (MMTV)-Wnt-1 transgenic mice (Wnt-1 TG), which develop mammary hyperplasia and neoplasia due to ectopic production of the Wnt-1 secretory glycoprotein. We have crossed these lines to ascertain the effects of ERa deficiency on mammary gland development and carcinogenesis in mice expressing the Wnt-1 transgene, Introduction of the Wnt-1 transgene into the ERKO background stimulates proliferation of alveolar-like epithelium, indicating that Wnt-1 protein can promote mitogenesis in the absence of an ER alpha-mediated response. The hyperplastic glandular tissue remains confined to the nipple region, implying that the requirement for EP alpha in ductal expansion is not overcome by ectopic Wnt-1, Tumors were detected in virgin ERKO females expressing the Wnt-1 transgene at an average age (48 weeks) that is twice that seen in virgin Wnt-1 TG mice (24 weeks) competent to produce ER alpha. Prepubertal ovariectomy of Wnt-1 TG mice also extended tumor latency to 42 weeks. However, pregnancy did not appear to accelerate the appearance of tumors in Wnt-1 TG mice, and tumor growth rates were not measurably affected by Late ovariectomy. Small hyperplastic mammary glands were observed in Wnt-1 TG males, regardless of ERa gene status; the glands were similar in appearance to those found in ERKO/Wnt-1 TG females. Mammary tumors also occurred in Wnt-1 TG males; latency tended to be Longer in the heterozygous ER alpha and ERKO males (86 to 100 weeks) than in wild-type ERa mice (ca. 75 weeks). We conclude that ectopic expression of the Wnt-1 proto- oncogene can induce mammary hyperplasia and tumorigenesis in the absence of ER alpha in female and male mice. The delayed time of tumor appearance may depend on the number of cells at risk of secondary events in the hyperplastic glands, on the carcinogenesis-promoting effects of ER alpha signaling, or on both. C1 NIEHS, Reprod & Dev Toxicol Lab, Receptor Biol Sect, NIH, Res Triangle Pk, NC 27709 USA. NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Korach, KS (reprint author), NIEHS, Reprod & Dev Toxicol Lab, Receptor Biol Sect, NIH, POB 12233,MD B302, Res Triangle Pk, NC 27709 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 62 TC 112 Z9 112 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 1999 VL 59 IS 8 BP 1869 EP 1876 PG 8 WC Oncology SC Oncology GA 187AZ UT WOS:000079764900014 PM 10213494 ER PT J AU Xu, XL Li, CL Takahashi, K Slavkin, HC Shum, L Deng, CX AF Xu, XL Li, CL Takahashi, K Slavkin, HC Shum, L Deng, CX TI Murine fibroblast growth factor receptor 1 alpha isoforms mediate node regression and are essential for posterior mesoderm development SO DEVELOPMENTAL BIOLOGY LA English DT Article DE gene targeting; FGFR1 alpha isoforms; morphogenetic movement; spina bifida ID MOUSE EMBRYO; LIMB DEVELOPMENT; LIGAND SPECIFICITY; CELL-MIGRATION; SONIC-HEDGEHOG; NERVOUS-SYSTEM; EXPRESSION; GASTRULATION; FGF8; GENE AB Alternative spicing in the fibroblast growth factor receptor 1 (Fgfr1) locus generates a variety of splicing isoforms, including FGFR1 alpha isoforms, which contain three immunoglobulin-like loops in the extracellular domain of the receptor. It has been previously shown that embryos carrying targeted disruptions of all major isoforms die during gastrulation, displaying severe growth retardation and defective mesodermal structures. Here we selectively disrupted the FGER1 alpha isoforms and found that they play an essential role in posterior mesoderm formation during gastrulation. We show that the mutant embryos lack caudal somites, develop spina bifida, and die at 9.5-12.5 days of embryonic development because they are unable to establish embryonic circulation. The primary defect is a failure of axial mesoderm cell migration toward the posterior portions of the embryos during gastrulation, as revealed by regional marker analysis and DiI labeling. In contrast, the anterior migration of the notochord is unaffected and the embryonic structures rostral to the forelimb are relatively normal. These data demonstrate that FGF/FGFR1 alpha signals are posteriorizing factors that control node regression and posterior embryonic development. (C) 1999 Academic Press. C1 NIDDKD, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA. NIAMSD, Craniofacial Dev Sect, NIH, Bethesda, MD 20892 USA. RP Deng, CX (reprint author), NIDDKD, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA. RI deng, chuxia/N-6713-2016 NR 64 TC 44 Z9 44 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD APR 15 PY 1999 VL 208 IS 2 BP 293 EP 306 DI 10.1006/dbio.1999.9227 PG 14 WC Developmental Biology SC Developmental Biology GA 189TX UT WOS:000079923200005 PM 10191046 ER PT J AU Xu, RH Ault, KT Kim, J Park, MJ Hwang, YS Peng, Y Sredni, D Kung, HF AF Xu, RH Ault, KT Kim, J Park, MJ Hwang, YS Peng, Y Sredni, D Kung, HF TI Opposite effects of FGF and BMP-4 on embryonic blood formation: Roles of PV.1 and GATA-2 SO DEVELOPMENTAL BIOLOGY LA English DT Article ID BONE MORPHOGENETIC PROTEIN-4; EARLY XENOPUS EMBRYO; HOMEOBOX GENE; HEMATOPOIETIC MESODERM; VENTRAL MESODERM; TGF-BETA; DIFFERENTIAL REGULATION; SIGNALING PATHWAYS; SPEMANN ORGANIZER; CELL DEVELOPMENT AB In adult vertebrates, fibroblast growth factor (FGF) synergizes with many hematopoietic cytokines to stimulate the proliferation of hematopoietic progenitors. In vertebrate development, the FGF signaling pathway is important in the formation of some derivatives of ventroposterior mesoderm. However, the function of FGF in the specification of the embryonic erythropoietic lineage has remained unclear. Here we address the role of FGF in the specification of the erythropoietic lineage in the Xenopus embryo. We report that ventral injection of embryonic FGF (eFGF) mRNA at as little as 10 pg at the four-cell stage suppresses ventral blood island (VBI) formation, whereas expression of the dominant negative form of the EGF receptor in the lateral mesoderm, where physiologically no blood tissue is formed, results in a dramatic expansion of the VBI. Similar results were observed in isolated ventral marginal zones and animal caps. Bone morphogenetic protein-4 (BMP-4) is known to induce erythropoiesis in the Xenopus embryo. Therefore, we examined how the BMP-4 and EGF signaling pathways might interact in the decision of ventral mesoderm to form blood. We observed that eFGF inhibits BMP-4-induced erythropoiesis by differentially regulating expression of the BMP-4 downstream effecters GATA-2 and PV.1. GATA-2 which stimulates erythropoiesis, is suppressed by FGF. PV.1, which we demonstrate to inhibit blood development, is enhanced by FGF. Additionally, PV.1 and GATA-2 negatively regulate transcription of each other. Thus, BMP-4 induces two transcription factors which have opposing effects on blood development. The EGF and BMP-4 signaling pathways interact to regulate the specification of the erythropoietic lineage. (C) 1999 Academic Press. C1 NCI, Lab Biochem Physiol, Div Basic Sci, Frederick, MD 21702 USA. NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. Hallym Univ, Coll Med, Dept Biochem, Chun Cheon, South Korea. Kyungpook Natl Univ, Sch Med, Dept Anat, Taegu 700422, South Korea. Bar Ilan Univ, Interdisciplinary Dept, IL-52900 Ramat Gan, Israel. Univ Hong Kong, Inst Mol Biol, Hong Kong, Hong Kong. RP Kung, HF (reprint author), NCI, Lab Biochem Physiol, Div Basic Sci, Frederick, MD 21702 USA. RI Xu, Ren-He/M-3125-2016 FU NCI NIH HHS [N01-CO-56000] NR 54 TC 41 Z9 44 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD APR 15 PY 1999 VL 208 IS 2 BP 352 EP 361 DI 10.1006/dbio.1999.9205 PG 10 WC Developmental Biology SC Developmental Biology GA 189TX UT WOS:000079923200009 PM 10191050 ER PT J AU Kellerman, KA McNally, JG AF Kellerman, KA McNally, JG TI Mound-cell movement and morphogenesis in Dictyostelium SO DEVELOPMENTAL BIOLOGY LA English DT Article DE morphogenesis; Dictyostelium; development; cell motion ID OPTICAL-SECTIONING MICROSCOPY; DISCOIDEUM; WAVES; PROPAGATION; AGGREGATION; GRADIENT; PHASE AB To examine the mechanisms of cell locomotion within a three-dimensional (3-D) cell mass, we have undertaken a systematic 3-D analysis of individual cell movements in the Dictyostelium mound, the first 3-D structure to form during development of the fruiting body. We used time-lapse deconvolution microscopy to examine two strains whose motion represents endpoints on the spectrum of motile behaviors that we have observed in mounds. In AX-2 mounds, cell motion is slow and trajectories are a combination of random and radial, compared to KAX-3, in which motion is fivefold faster and most trajectories are rotational. Although radial or rotational motion was correlated with the optical-density wave patterns present in each strain, we also found small but significant subpopulations of cells that moved differently from the majority, demonstrating that optical-density waves are at best insufficient to explain all motile behavior in mounds. In examining morphogenesis in these strains, we noted that AX-2 mounds tended to culminate directly to a fruiting body, whereas KAX-3 mounds first formed a migratory slug. By altering buffering conditions we could interchange these behaviors and then found that mound-cell motions also changed accordingly. This demonstrates a correlation between mound-cell motion and subsequent development, but it is not obligatory. Chimeric mounds composed of only 10% KAX-3 cells and 90% AX-2 cells exhibited rotational motion, suggesting that a diffusible molecule induces rotation, but many of these mounds still culminated directly, demonstrating that rotational motion does not always lead to slug migration. Our observations provide a detailed analysis of cell motion for two distinct modes of mound and slug formation in Dictyostelium. (C) 1999 Academic Press. C1 Washington Univ, Dept Biol, St Louis, MO 63130 USA. Washington Univ, Inst Biomed Comp, St Louis, MO 63130 USA. RP McNally, JG (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, 41 Lib Dr,MSC 5055, Bethesda, MD 20892 USA. FU NIGMS NIH HHS [GM 47330] NR 25 TC 17 Z9 17 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD APR 15 PY 1999 VL 208 IS 2 BP 416 EP 429 DI 10.1006/dbio.1999.9208 PG 14 WC Developmental Biology SC Developmental Biology GA 189TX UT WOS:000079923200014 PM 10191055 ER PT J AU Zhang, JM Chen, LS Krause, M Fire, A Paterson, BM AF Zhang, JM Chen, LS Krause, M Fire, A Paterson, BM TI Evolutionary conservation of MyoD function and differential utilization of E proteins SO DEVELOPMENTAL BIOLOGY LA English DT Article DE MyoD; E proteins; myogenesis; Drosophila; C-elegans ID SEX DETERMINATION GENE; REGULATORY FACTORS; MUSCLE DEVELOPMENT; HOMOLOG HLH-1; BHLH PROTEINS; DROSOPHILA; DAUGHTERLESS; FAMILY; CELLS; EXPRESSION AB The formation of striated muscle in both vertebrates and invertebrates involves the activity of the MyoD family of basic-helix-loop-helix (bHLH) transcription factors. The high degree of evolutionary conservation of MyoD-related proteins, both in the sequence of their bHLH domains and in their general developmental expression patterns, suggests that these factors are also conserved at the level of function. We have addressed this directly using MyoD and E protein factors from vertebrates, Drosophila, and Caenorhabditis elegans. Various MyoD and E factor combinations were tested for their ability to interact in vitro and to function in vivo in the myogenic conversion of 10T1/2 mouse fibroblasts. We found that the ability of different homo- and heterodimers to bind DNA in vitro was an accurate measure of biological activity in vivo. A second assessment of conserved function comes from the ability of these factors to rescue a C. elegans hlh-1 (CeMyoD) null mutation. We found that both Drosophila and chicken MyoD-related factors were able to rescue a C. elegans CeMyoD loss-of-function mutation. These results demonstrate a remarkable degree of functional conservation of these myogenic factors despite differences in E-protein interactions. (C) 1999 Academic Press. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. Carnegie Inst Washington, Dept Embryol, Baltimore, MD 21210 USA. RP Paterson, BM (reprint author), NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. OI Krause, Michael/0000-0001-6127-3940 NR 36 TC 28 Z9 30 U1 1 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD APR 15 PY 1999 VL 208 IS 2 BP 465 EP 472 DI 10.1006/dbio.1999.9218 PG 8 WC Developmental Biology SC Developmental Biology GA 189TX UT WOS:000079923200018 PM 10191059 ER PT J AU Guo, S Wilson, SW Cooke, S Chitnis, AB Driever, W Rosenthal, A AF Guo, S Wilson, SW Cooke, S Chitnis, AB Driever, W Rosenthal, A TI Mutations in the zebrafish unmask shared regulatory pathways controlling the development of catecholaminergic neurons SO DEVELOPMENTAL BIOLOGY LA English DT Article ID HYDROXYLASE-IMMUNOREACTIVE NEURONS; SONIC HEDGEHOG; LOCUS-COERULEUS; CAROTID-BODY; EMBRYONIC ZEBRAFISH; BRACHYDANIO-RERIO; FLOOR PLATE; CELLS; INDUCTION; BRAIN AB The mechanism by which pluripotent progenitors give rise to distinct classes of mature neurons in vertebrates is not well understood. To address this issue we undertook a genetic screen for mutations which affect the commitment and differentiation of catecholaminergic (CA) [dopaminergic (DA), noradrenergic (NA), and adrenergic] neurons in the zebrafish, Danio rerio. The identified mutations constitute five complementation groups, motionless and foggy affect the number and differentiation state of hypothalamic DA, telencephalic DA, retinal DA, locus coeruleus (LC) NA, and sympathetic NA neurons. The too few mutation leads to a specific reduction in the number of hypothalamic DA neurons, no soul lacks arch-associated NA cells and has defects in pharyngeal arches, and soulless lacks both arch-associated and LC cell groups. Our analyses suggest that the genes defined by these mutations regulate different steps in the differentiation of multipotent CA. progenitors. They further reveal an underlying universal mechanism for the control of CA cell fates, which involve combinatorial usage of regulatory genes. (C) 1999 Academic Press. C1 Genentech Inc, Dept Neurosci, San Francisco, CA 94080 USA. UCL, Dept Anat & Dev Biol, London WC1E 6BT, England. NICHD, Unit Vertebrate Neural Dev, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. Univ Freiburg, Inst Biol 1, D-79104 Freiburg, Germany. RP Rosenthal, A (reprint author), Genentech Inc, Dept Neurosci, 1 DNA Way, San Francisco, CA 94080 USA. EM ar@gene.com RI Wilson, Stephen/B-9404-2008; Zebrafish, UCL/A-3125-2009; OI Wilson, Stephen/0000-0002-8557-5940; cooke, samuel/0000-0002-4876-6502 FU Wellcome Trust NR 40 TC 166 Z9 167 U1 2 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD APR 15 PY 1999 VL 208 IS 2 BP 473 EP 487 DI 10.1006/dbio.1999.9204 PG 15 WC Developmental Biology SC Developmental Biology GA 189TX UT WOS:000079923200019 PM 10191060 ER PT J AU Paria, BC Zhao, XM Das, SK Dey, SK Yoshinaga, K AF Paria, BC Zhao, XM Das, SK Dey, SK Yoshinaga, K TI Zonula occludens-1 and E-cadherin are coordinately expressed in the mouse uterus with the initiation of implantation and decidualization SO DEVELOPMENTAL BIOLOGY LA English DT Article DE ZO-1; E-cadherin; implantation; uterus; embryo; mouse ID JUNCTION-ASSOCIATED PROTEIN; CELL-ADHESION MOLECULE; TIGHT JUNCTION; EPITHELIAL-CELLS; CDNA CLONING; PERIIMPLANTATION PERIOD; RAT UTERUS; ZO-1; PERMEABILITY; GENE AB Two-way interactions between the blastocyst trophectoderm and the uterine luminal epithelium are essential for implantation. The key events of this process are cell-cell contact of trophectoderm cells with uterine luminal epithelial cells, controlled invasion of trophoblast cells through the luminal epithelium and the basement membrane, transformation of uterine stromal cells surrounding the blastocyst into decidual cells, and protection of the "semiallogenic" embryo from the mother's immunological responses. Because cell-cell contact between the trophectoderm epithelium and the luminal epithelium is essential for implantation, we investigated the expression of zonula occludens-1 (ZO-1) and E-cadherin, two molecules associated with epithelial cell junctions, in the mouse uterus during the periimplantation period. Preimplantation uterine epithelial cells express both ZO-1 and E-cadherin. With the initiation and progression of implantation, ZO-1 and E-cadherin are expressed in stromal cells of the primary decidual zone (PDZ). As trophoblast invasion progresses, these two molecules are expressed in stroma in advance of the invading trophoblast cells. These results suggest that expression of these adherence and tight junctions molecules in the PDZ serves to function as a permeability barrier to regulate access of immunologically competent maternal cells and/or molecules to the embryo and provide homotypic guidance of trophoblast cells in the endometrium. (C) 1999 Academic Press. C1 Univ Kansas, Med Ctr, Dept Mol & Integrat Physiol, Ralph L Smith Res Ctr, Kansas City, KS 66160 USA. NICHHD, Reprod Sci Branch, NIH, Bethesda, MD 20892 USA. RP Paria, BC (reprint author), Univ Kansas, Med Ctr, Dept Mol & Integrat Physiol, Ralph L Smith Res Ctr, Kansas City, KS 66160 USA. FU NICHD NIH HHS [HD12304, HD35114, HD29968] NR 58 TC 79 Z9 85 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD APR 15 PY 1999 VL 208 IS 2 BP 488 EP 501 DI 10.1006/dbio.1999.9206 PG 14 WC Developmental Biology SC Developmental Biology GA 189TX UT WOS:000079923200020 PM 10191061 ER PT J AU Brendler, T Austin, S AF Brendler, T Austin, S TI Binding of SeqA protein to DNA requires interaction between two or more complexes bound to separate hemimethylated GATC sequences SO EMBO JOURNAL LA English DT Article DE DNA binding; GATC sequences; hemimethylation; SeqA protein ID ESCHERICHIA-COLI; CHROMOSOMAL REPLICATION; DAM METHYLTRANSFERASE; RNA-POLYMERASE; ORIGIN; INITIATION; METHYLATION; RECOGNITION; PROMOTER; PREVENTS AB The SeqA protein binds to the post-replicative forms of the origins of replication of the Escherichia coli chromosome (oriC) and the P1 plasmid (P1oriR) at hemimethylated GATC adenine methylation sites. It appears to regulate replication by preventing premature reinitiation. However, SeqA binding is not exclusive to replication origins: different fragments with hemimethylated GATC sites can bind SeqA in vitro when certain rules apply. Most notably, more than one such site must be present on a bound fragment. The protein appears to recognize individual hemimethylated sites, but must undergo an obligate cooperative interaction with a nearby bound protein for stable binding. SeqA contacts both DNA strands in a discrete patch at each hemimethylated GATC sequence. All four GATC bases are contacted and are essential for binding. Although the recognized sequence is symmetrical, the footprint on the methylated strand is always broader, suggesting that the bound protein is positioned asymmetrically with its orientation dictated by the position of the unique methyl group. Studies of alternative spacings and relative orientations of adjacent sites suggest that each site may be recognized by a symmetrical dimer with an induced asymmetry in one of the subunits similar to that seen with certain type II restriction endonucleases. C1 NCI, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Austin, S (reprint author), NCI, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. EM austin@ncifcrf.gov NR 22 TC 81 Z9 81 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD APR 15 PY 1999 VL 18 IS 8 BP 2304 EP 2310 DI 10.1093/emboj/18.8.2304 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 190JK UT WOS:000079959200028 PM 10205183 ER PT J AU Zucchi, I Jones, J Affer, M Montagna, C Redolfi, E Susani, L Vezzoni, P Parvari, R Schlessinger, D Whyte, MP Mumm, S AF Zucchi, I Jones, J Affer, M Montagna, C Redolfi, E Susani, L Vezzoni, P Parvari, R Schlessinger, D Whyte, MP Mumm, S TI Transcription map of Xq27: Candidates for several X-linked diseases SO GENOMICS LA English DT Article ID RECESSIVE IDIOPATHIC HYPOPARATHYROIDISM; MENTAL-RETARDATION; HUMAN GENOME; YAC/STS MAP; CPG ISLAND; GENE; IDENTIFICATION; CHROMOSOME; LOCALIZATION; RESOLUTION AB Human Xq27 contains candidate regions for several disorders, yet is predicted to be a gene-poor cytogenetic band. We have developed a transcription map for the entire cytogenetic band to facilitate the identification of the relatively small number of expected candidate genes. Two approaches were taken to identify genes: (1) a group of 64 unique STSs that were generated during the physical mapping of the region were used in RT-PCR with RNA from human adult and fetal brain and (2) ESTs that have been broadly mapped to this region of the chromosome were finely mapped using a high-resolution yeast artificial chromosome contig. This combined approach identified four distinct regions of transcriptional activity within the Xq27 band. Among them is a region at the centromeric boundary that contains candidate regions for several rare developmental disorders (X-linked recessive hypoparathyroidism, thoracoabdominal syndrome, albinism-deafness syndrome, and Borjeson-Forssman-Lehman syndrome). Two transcriptionally active regions were identified in the center of Xq27 and include candidate regions for X-linked mental retardation syndrome 6, X-linked progressive cone dystrophy, X-linked retinitis pigmentosa 24, and a prostate cancer susceptibility locus. The fourth region of transcriptional activity encompasses the FMR1 (FRAXA) and FMR2 (FRAXE) genes. The analysis thus suggests clustered transcription in Xq27 and provides candidates for several heritable disorders for which the causative genes have not yet been found. (C) 1999 Academic Press. C1 CNR, Ist Tecnol Biomed Avanzate, I-20131 Milan, Italy. Washington Univ, Sch Med, Div Bone & Mineral Dis, St Louis, MO 63110 USA. Soroka Med Ctr, Clin Genet Unit, IL-84101 Beer Sheva, Israel. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Mumm, S (reprint author), Washington Univ, Sch Med, Div Bone & Mineral Dis, 216 S Kingshighway Blvd,Box 8301, St Louis, MO 63110 USA. FU NICHD NIH HHS [HD33013]; Telethon [E.0415] NR 39 TC 12 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD APR 15 PY 1999 VL 57 IS 2 BP 209 EP 218 DI 10.1006/geno.1999.5768 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 188VF UT WOS:000079868900003 PM 10198160 ER PT J AU Robb, L Brodnicki, T Copeland, NG Gilbert, DJ Jenkins, NA Harvey, RP AF Robb, L Brodnicki, T Copeland, NG Gilbert, DJ Jenkins, NA Harvey, RP TI Assignment of the human helix-loop-helix transcription factor gene Musculin/Activated B-Cell factor-1 (MSC) to chromosome 8q21 and its mouse homologue (Msc) to the proximal region of chromosome 1 SO GENOMICS LA English DT Article ID LYMPHOCYTES; GENOME; MAP C1 Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. St Vincents Hosp, Victor Chang Cardiac Res Inst, Darlinghurst, NSW 2010, Australia. RP Robb, L (reprint author), Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia. NR 5 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 0888-7543 J9 GENOMICS JI Genomics PD APR 15 PY 1999 VL 57 IS 2 BP 318 EP 319 DI 10.1006/geno.1999.5764 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 188VF UT WOS:000079868900019 PM 10198176 ER PT J AU Hanson, IC Antonelli, TA Sperling, RS Oleske, JM Cooper, E Culnane, M Fowler, MG Kalish, LA Lee, SS McSherry, G Mofenson, L Shapiro, DE AF Hanson, IC Antonelli, TA Sperling, RS Oleske, JM Cooper, E Culnane, M Fowler, MG Kalish, LA Lee, SS McSherry, G Mofenson, L Shapiro, DE TI Lack of tumors in infants with perinatal HIV-1 exposure and fetal/neonatal exposure to zidovudine SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE perinatal HIV transmission; zidovudine; perinatal HIV transmission prophylaxis carcinogenesis ID HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSMISSION; REDUCTION; IMPACT; MICE AB Zidovudine (ZDV) therapy during pregnancy and to the neonate reduced perinatal HIV transmission by nearly 70% in Pediatric AIDS Clinical Trials Group (PACTG) protocol 076. ZDV has been reported as positive in several in vitro carcinogenicity screening tests. We evaluated the short-term risk for tumors in 727 children with known ZDV exposure enrolled into the PACTG 076/219 and the Women and Infants Transmission Study (WITS). ZDV exposure in utero (antepartum) occurred in 97% and 99% of infants in PACTG 076/219 or WITS, respectively. Mean follow-up was 38.3 months with 366.9 person years follow-up for PACTC 076/219 and 14.5 months with 743.7 person years follow-up for WITS. No tumors of any nature were observed; relative risk was 0 (95% confidence interval [CI], 0-17.6). These data are reassuring regarding the short-term lack of tumors for ZDV-exposed infants observed to date. Longitudinal, standardized follow-up for infants with in utero antiretroviral exposure is necessary to assess long-term carcinogenicity. C1 Baylor Coll Med, Houston, TX 77030 USA. New England Res Inst, Watertown, MA 02172 USA. Mt Sinai Sch Med, New York, NY USA. Univ Med & Dent New Jersey, Sch Med, Newark, NJ 07103 USA. Boston Med Ctr, Boston, MA USA. NIAID, Pediat Med Branch, Div Aids, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Ctr Biostat AIDS Res, Boston, MA 02115 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Hanson, IC (reprint author), Texas Childrens Hosp, 6621 Fannin MC 1-3291, Houston, TX 77030 USA. RI Oleske, James/C-1951-2016; OI Oleske, James/0000-0003-2305-5605; Mofenson, Lynne/0000-0002-2818-9808 FU NIAID NIH HHS [UO1 AI 34856, UO1 AI 34842, UO1 AI 34858] NR 14 TC 74 Z9 76 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD APR 15 PY 1999 VL 20 IS 5 BP 463 EP 467 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 189EX UT WOS:000079892400008 PM 10225228 ER PT J AU Ahmad, F Gao, G Wang, LM Landstrom, TR Degerman, E Pierce, JH Manganiello, VC AF Ahmad, F Gao, G Wang, LM Landstrom, TR Degerman, E Pierce, JH Manganiello, VC TI IL-3 and IL-4 activate cyclic nucleotide phosphodiesterases 3 (PDE3) and 4 (PDE4) by different mechanisms in FDCP2 myeloid cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-KINASE-B; GLYCOGEN-SYNTHASE KINASE-3; COLONY-STIMULATING FACTOR; P70 S6 KINASE; CAMP-SPECIFIC PHOSPHODIESTERASE; DEPENDENT HEMATOPOIETIC-CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNAL-TRANSDUCTION; TYROSINE PHOSPHORYLATION; 3T3-L1 ADIPOCYTES AB In FDCP2 myeloid cells, IL-4 activated cyclic nucleotide phosphodiesterases PDE3 and PDE4, whereas IL-3, granulocyte-macrophage CSF (GM-CSF), and phorbol ester (PMA) selectively activated PDE4. IL-4 (not IL-3 or GM-CSF) induced tyrosine phosphorylation of insulin-receptor substrate-2 (IRS-2) and its association with phosphatidylinositol 3 kinase (PI3-K). TNF-alpha, AG-490 (Janus kinase inhibitor), and wortmonnin (PI3-K inhibitor) inhibited activation of PDE3 and PDE4 by, IL-4. TNF-alpha also blocked IL-4-induced tyrosine phosphorylation of IRS-2, but not of STAT6. AG-490 and wortmannin, not TNF-alpha, inhibited activation of PDE4 by IL-3, These results suggested that IL-4-induced activation of PDE3 and PDE4 Has downstream of IRS-2/ PI3-K, not STAT6, and that inhibition of tyrosine phosphorylation! of IRS molecules might be one mechanism a whereby TNF-alpha could selectively regulate activities of cytokines that utilized IRS proteins as signal transducers. RO31-7549 (protein kinase C (PKC) inhibitor) inhibited activation of PDE4 by PMA. IL-4, IL-3, and GM-CSF activated mitogen mitogen-activated protein (MAP)] kinase and protein kinase B via PI3-K signals; PMA activated only. MAP kinase r ia PF;C signals, The MAP kinase kinase (MEK-1) inhibitor PD98059 inhibited IL-4-, IL-3-, and PMA-induced activation of MAP kinase and PDE4, but not IL-4-induced activation of PDES. In FDCP2 cells transfected with constitutively activated MEK, MAP kinase and PDE4, not PDE3, Here activated, Thus, in FDCP2 cells, PDE4 can be activated by overlapping. MAP kinase-dependent pathways involving PI3-K (IL-4, IL-3, GM-CSF) or PKC (PMA), but selective activation of PDE3 by IL-4 is MAP kinase independent (but perhaps IRS-2/PI3-K dependent). C1 NHLBI, PCCMB, NIH, Bethesda, MD 20892 USA. NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Lund, Sect Mol Signaling, Dept Cellular & Mol Biol, Lund, Sweden. RP Manganiello, VC (reprint author), NHLBI, PCCMB, NIH, Bldg 10,Room 5n-307,10 Ctr Dr,MSC 1434, Bethesda, MD 20892 USA. EM manganiv@gwgale.nhlbi.nih.gov NR 80 TC 36 Z9 38 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 APR 15 PY 1999 VL 162 IS 8 BP 4864 EP 4875 PG 12 WC Immunology SC Immunology GA 184KV UT WOS:000079612100062 PM 10202031 ER PT J AU Zou, JP Morford, LA Chougnet, C Dix, AR Brooks, AG Torres, N Shuman, JD Coligan, JE Brooks, WH Roszman, TL Shearer, GM AF Zou, JP Morford, LA Chougnet, C Dix, AR Brooks, AG Torres, N Shuman, JD Coligan, JE Brooks, WH Roszman, TL Shearer, GM TI Human glioma-induced immunosuppression involves soluble factor(s) that alters monocyte cytokine profile and surface markers SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PRIMARY INTRACRANIAL TUMORS; MESSENGER-RNA EXPRESSION; MITOGEN-ACTIVATED LYMPHOCYTES; HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL PROLIFERATION; GROWTH FACTOR-BETA; INTERFERON-GAMMA; DENDRITIC CELLS; ANTIGEN PRESENTATION; METASTATIC MELANOMA AB Patients with gliomas exhibit deficient in vitro and in vivo T cell, immune activity, and human glioblastoma culture supernatants (GCS) inhibit in vitro T lymphocyte responses. Because APC are essential for initiating and regulating T cell responses, we investigated whether GCS would affect cytokines produced by monocytes and T cells from healthy donors of PBMC. Incubation of PBMC with GCS decreased production of IL-12, IFN-gamma and TNF-alpha, and increased production of IL-6 and IL-10, The GCS-induced changes in IL-12 and IL-10 occurred in monocytes, and involved changes in IL-12 p40 and IL-10 mRNA expression, Incubation with GCS also resulted in reduced expression of,MHC class II and of CD80/86 costimulatory molecules on monocytes. The immunosuppressive effects Here not the result of IL-6 or TGF-beta 1 that was detected in SCS, However, it was due to a factor(s) that is resistant to pH extremes, differentially susceptible to temperature, susceptible to trypsin, and has a minimum molecular mass of 40 kDa. Our findings show that glioblastoma-generated factors that are known to suppress T cell responses alter the cytokine profiles of monocytes APC that, in turn, inhibit T cell function, This model indicates that monocytes can serve as an intermediate between tumor-generated immune-suppressive factors and the T cell responses that are suppressed in gliomas. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Kentucky, Med Ctr, Dept Microbiol & Immunol, Lexington, KY 40536 USA. NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Shearer, GM (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B-36, Bethesda, MD 20892 USA. EM gene_shearer@nih.gov NR 60 TC 100 Z9 103 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1999 VL 162 IS 8 BP 4882 EP 4892 PG 11 WC Immunology SC Immunology GA 184KV UT WOS:000079612100064 PM 10202033 ER EF