FN Thomson Reuters Web of Science™ VR 1.0 PT J AU FarkasSzallasi, T Bennett, GJ Blumberg, PM Hokfelt, T Lundberg, JM Szallasi, A AF FarkasSzallasi, T Bennett, GJ Blumberg, PM Hokfelt, T Lundberg, JM Szallasi, A TI Vanilloid receptor loss is independent of the messenger plasticity that follows systemic resiniferatoxin administration SO BRAIN RESEARCH LA English DT Article DE messenger plasticity; axotomy; chronic constriction injury rat; vanilloid receptor; resiniferatoxin ID NERVE GROWTH-FACTOR; DORSAL-ROOT GANGLIA; PRIMARY SENSORY NEURONS; PERIPHERAL AXOTOMY; SPINAL-CORD; ADULT-RAT; CAPSAICIN-SENSITIVITY; INSITU HYBRIDIZATION; SUBSTANCE-P; IMMUNOREACTIVITY AB Resiniferatoxin (RTX) depletes vanilloid (capsaicin) receptors from lumbar dorsal root ganglia (DRG) of the rat. In addition, RTX causes changes in neuropeptide and nitric oxide synthase expression in lumbar DRG neurons, similar to those described following axotomy; this latter phenomenon is referred to as messenger plasticity. These findings suggested that vanilloid receptor loss may be part of the plasticity that follows RTX treatment. Here we show that vanilloid receptor expression, as detected by [H-3]RTX autoradiography, is not changed in lumbar DRGs of axotomized rats, nor is it altered in a rat model (chronic constriction injury) of neuropathic pain. Thus, the in vivo expression of vanilloid receptors detected by specific [H-3]RTX binding does not require the presence of intraaxonally transported trophic factors such as nerve growth factor. We conclude that messenger plasticity and vanilloid receptor loss are mediated by distinct mechanisms. C1 KAROLINSKA INST,DEPT PHARMACOL,S-17177 STOCKHOLM,SWEDEN. KAROLINSKA INST,DEPT NEUROSCI,S-17177 STOCKHOLM,SWEDEN. NIDR,NIH,BETHESDA,MD 20892. NCI,NIH,BETHESDA,MD 20892. NR 39 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 6 PY 1996 VL 719 IS 1-2 BP 213 EP 218 DI 10.1016/0006-8993(96)00065-0 PG 6 WC Neurosciences SC Neurosciences & Neurology GA UP705 UT WOS:A1996UP70500029 PM 8782884 ER PT J AU Sato, H Takino, T Kinoshita, T Imai, K Okada, Y Stevenson, WGS Seiki, M AF Sato, H Takino, T Kinoshita, T Imai, K Okada, Y Stevenson, WGS Seiki, M TI Cell surface binding and activation of gelatinase A induced by expression of membrane-type-1-matrix metalloproteinase (MT1-MMP) SO FEBS LETTERS LA English DT Article DE metalloproteinase; activation; binding ID IV COLLAGENASE GENE; MATRIX METALLOPROTEINASES; TISSUE INHIBITOR; FIBROBLASTS; ASSOCIATION; METASTASIS; MEMBRANES; CARCINOMA; MECHANISM AB Gelatinase A is secreted as a proenzyme (progelatinase A) which is activated and bound on the surface of tumor and normal cells. We have reported that the expression of a membrane-type-1-matrix metalloproteinase (MT1-MMP) induces activation of progelatinase A. Here we demonstrate that the expression of MT1-MMP in COS-1 cells induces cell-surface binding of progelatinase A which is consequently processed to an intermediate form. Processing from the intermediate to the fully active form is dependent on the gelatinase A concentration. These results suggest that the cell-surface binding concentrates the gelatinase A intermediate form locally to allow autoproteolytic processing to the fully active form. C1 KANAZAWA UNIV,CANC RES INST,DEPT MOLEC IMMUNOL,KANAZAWA,ISHIKAWA 920,JAPAN. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. RP Sato, H (reprint author), KANAZAWA UNIV,CANC RES INST,DEPT MOLEC ONCOL & VIROL,13-1 TAKARAMACHI,KANAZAWA,ISHIKAWA 920,JAPAN. RI Imai, Kazushi/E-7206-2012; Okada, Yasunori/B-5550-2014; Stetler-Stevenson, William/H-6956-2012; TAKINO, Takahisa/D-8460-2015; Seiki, Motoharu/K-9443-2015; SATO, Hiroshi/D-8454-2015 OI Okada, Yasunori/0000-0001-9208-4755; Stetler-Stevenson, William/0000-0002-5500-5808; NR 27 TC 158 Z9 163 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAY 6 PY 1996 VL 385 IS 3 BP 238 EP 240 DI 10.1016/0014-5793(96)00389-4 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA UK228 UT WOS:A1996UK22800023 PM 8647259 ER PT J AU Bramham, CR Southard, T Sarvey, JM Herkenham, M Brady, LS AF Bramham, CR Southard, T Sarvey, JM Herkenham, M Brady, LS TI Unilateral LTP triggers bilateral increases in hippocampal neurotrophin and trk receptor mRNA expression in behaving rats: Evidence for interhemispheric communication SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE synaptic plasticity; gene expression; long-term potentiation; growth factor; tyrosine kinase receptor ID LONG-TERM POTENTIATION; NERVE GROWTH-FACTOR; MESSENGER-RNA EXPRESSION; PROTEIN-SYNTHESIS; SYNAPTIC PLASTICITY; MOLECULAR-CLONING; DENTATE GYRUS; BRAIN; BDNF; INDUCTION AB Induction of long-term potentiation (LTP) in the dentate gyrus of awake rats triggered a rapid (2 hour) elevation in tyrosine kinase receptor (trkB and trkC) gene expression and a delayed (6-24 hour) increase in brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) gene expression. Depending on the mRNA species, LTP induction led to highly selective unilateral or bilateral increases in gene expression. Specifically, trkB and NT-3 mRNA elevations were restricted to granule cells in the ipsilateral dentate gyrus, whereas bilateral increases in trkC, BDNF, and nerve growth factor (NGF) mRNA levels occurred in granule cells and hippocampal pyramidal cells. Both unilateral and bilateral changes in gene expression were N-methyl-D-aspartate (NMDA) receptor-dependent and LTP-specific. Bilateral electrophysiological recordings demonstrated that LTP was unilaterally induced; this was corroborated by a dramatic unilateral increase in the expression of the immediate early gene zif/268, a marker for LTP, restricted to the ipsilateral granule cells. The results indicate that LTP triggers an interhemispheric communication manifested as selective, bilateral increases in gene expression at multiple sites in the hippocampal network. Furthermore, our findings suggest that physiological plastic changes in the adult brain may involve coordinated, time-dependent regulation of multiple neurotrophin and trh receptor genes. (C) 1996 Wiley-Liss, Inc. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PHARMACOL,BETHESDA,MD 20814. NIMH,FUNCT NEUROANAT SECT,BETHESDA,MD 20892. RI yu, yan/C-2322-2012; OI Herkenham, Miles/0000-0003-2228-4238; Bramham, Clive/0000-0001-5958-7115 FU NINDS NIH HHS [NS23865] NR 59 TC 108 Z9 110 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD MAY 6 PY 1996 VL 368 IS 3 BP 371 EP 382 PG 12 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA UG860 UT WOS:A1996UG86000004 PM 8725345 ER PT J AU Kharazia, VN Wenthold, RJ Weinberg, RJ AF Kharazia, VN Wenthold, RJ Weinberg, RJ TI GluR1-immunopositive interneurons in rat neocortex SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE AMPA; GABA; GluR2; S-1; colocalization ID GLUTAMATE-RECEPTOR SUBUNITS; EXCITATORY POSTSYNAPTIC POTENTIALS; GAMMA-AMINOBUTYRIC-ACID; CEREBRAL-CORTEX; HIPPOCAMPAL-NEURONS; VISUAL-CORTEX; BRAIN; NMDA; GABA; NEUROPEPTIDES AB Recent in vitro studies suggest that inhibitory interneurons in cortex may express the GluR1 glutamate receptor subunit in the absence of GluR2, leading to calcium-permeable alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) channels. We performed a study of rat somatic sensory cortex to confirm and extend these observations, using quantitative immunocytochemistry for multiple antigens. A morphologically distinct subpopulation of nonpyramidal neurons in neocortex was intensely immunoreactive for GluR1. Electron microscopic analysis of these cells revealed somatic staining for GluR1, mainly in the rough endoplasmic reticulum. Dendritic staining was concentrated at the synaptic active zone and in the adjacent subsynaptic cytoplasm. Double immunostaining revealed that the large majority of intensely GluR1-positive cells contained gamma-aminobutyric acid or its synthetic enzyme, glutamic acid decarboxylase, but little or no GluR2. Thus, AMPA receptors on a subpopulation of inhibitory interneurons in cortex are likely to be calcium permeable. This calcium permeability is likely to influence functional properties of these neurons; it may underlie the high levels of calcium-binding proteins they contain; and may render them liable to excitotoxic injury. (C) 1996 Wiley-Liss, Inc. C1 NIDCD,NEUROCHEM LAB,NIH,BETHESDA,MD. RP Kharazia, VN (reprint author), UNIV N CAROLINA,DEPT CELL BIOL & ANAT,CB 7090,CHAPEL HILL,NC 27599, USA. FU NINDS NIH HHS [NS-29879] NR 62 TC 51 Z9 52 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD MAY 6 PY 1996 VL 368 IS 3 BP 399 EP 412 DI 10.1002/(SICI)1096-9861(19960506)368:3<399::AID-CNE6>3.0.CO;2-0 PG 14 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA UG860 UT WOS:A1996UG86000006 PM 8725347 ER PT J AU Bokesch, HR McKee, TC Cardellina, JH Boyd, MR AF Bokesch, HR McKee, TC Cardellina, JH Boyd, MR TI Suberosenone, a new cytotoxin from Subergorgia suberosa SO TETRAHEDRON LETTERS LA English DT Article ID ASPERGILLUS-TERREUS AB The organic extract of the gorgonian Subergorgia suberosa was found to contain a novel cytotoxic sesquiterpene, suberosenone (1), as well as two known piscicidal sesquiterpenes, buddledins C and D. The structure of 1 was defined by spectral methods, including 1D and 2D NMR experiments. Suberosenone, the first quadrone-class sesquiterpene from the marine biosphere, exhibited relatively potent cytotoxicity to solid tumor lines in comparison to leukemia lines in the NCI's 60 cell line in vitro screen. Published by Elsevier Science Ltd. C1 NCI, LAB DRUG DISCOVERY RES & DEV, DEV THERAPEUT PROGRAM, DIV CANC TREATMENT DIAGNOSIS & CTR, FREDERICK, MD 21701 USA. NR 7 TC 42 Z9 44 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD MAY 6 PY 1996 VL 37 IS 19 BP 3259 EP 3262 DI 10.1016/0040-4039(96)00528-X PG 4 WC Chemistry, Organic SC Chemistry GA UJ581 UT WOS:A1996UJ58100013 ER PT J AU McKusick, VA Amberger, JS Francomano, CA AF McKusick, VA Amberger, JS Francomano, CA TI Progress in medical genetics: Map-based gene discovery and the molecular pathology of skeletal dysplasias SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article C1 NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP McKusick, VA (reprint author), JOHNS HOPKINS UNIV HOSP,CTR GENET MED,BALTIMORE,MD 21287, USA. NR 4 TC 9 Z9 9 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAY 3 PY 1996 VL 63 IS 1 BP 98 EP 105 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA UH939 UT WOS:A1996UH93900019 PM 8723094 ER PT J AU Pericle, F Kirken, RA EplingBurnette, PK Blanchard, DK Djeu, JY AF Pericle, F Kirken, RA EplingBurnette, PK Blanchard, DK Djeu, JY TI Direct killing of interleukin-2-transfected tumor cells by human neutrophils SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID POLYMORPHONUCLEAR LEUKOCYTES; MAMMARY ADENOCARCINOMA; MONOCLONAL-ANTIBODY; CYTO-TOXICITY; L-ARGININE; MECHANISM; GAMMA; IL-2; CYTOTOXICITY; MODULATION AB We have previously established that human polymorphonuclear cells (PMN) express IL-2R beta- and gamma-chains and that addition of IL-2 maintains the viability of PMN by preventing these cells from undergoing programmed cell death. The purpose of this study was to examine whether IL-2-releasing tumor cells are capable of stimulating PMN tumoricidal activity. We therefore investigated the ability of PMN to kill IL-2-transfected tumor cells using normal human PMN directed against the murine mammary adenocarcinoma TS/A engineered to release high amounts of murine IL-2 (3,600 U, B6) compared with TS/A parental cells and TS/A tumor cells transfected with the neomycin-resistance (NEO) gene only. The potency of PMN as IL-2-induced killer cells was indicated by the low number of cells required for killing (effector cell:target cell ratio 10:1) and the degree of tumor cell lysis (68 +/- 10%). Evidence for the role of IL-2 as a mediator of tumor cytotoxicity by PMN was substantiated by inhibition of tumor killing with anti-IL-2 and anti-IL-2R beta monoclonal antibodies (MAbs). Furthermore, in vivo depletion of mature granulocytes using MAb RB6-8C5 resulted in Bb adenocarcinoma growth, thereby confirming a direct role for IL-2-activated PMN in tumor cytolysis. Lastly, we suggest that one possible mechanism involved in IL-2-induced PMN cytotoxicity against the Bb clone occurs via the nitric oxide pathway, which could be inhibited upon addition of the arginine analog, N-G-monomethyl-L-arginine. (C) 1996 Wiley-Liss, Inc. C1 NCI, FREDERICK CANC RES & DEV CTR, CYTOKINE MOL MECHANISMS SECT, FREDERICK, MD USA. UNIV S FLORIDA, COLL MED, H LEE MOFFITT CANC CTR & RES INST, PROGRAM IMMUNOL, TAMPA, FL USA. RP Pericle, F (reprint author), NCI, NIH, EXPTL IMMUNOL BRANCH, BLDG 10, ROOM 4B-17, BETHESDA, MD 20892 USA. NR 37 TC 26 Z9 28 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 3 PY 1996 VL 66 IS 3 BP 367 EP 373 DI 10.1002/(SICI)1097-0215(19960503)66:3<367::AID-IJC17>3.0.CO;2-8 PG 7 WC Oncology SC Oncology GA UG986 UT WOS:A1996UG98600017 PM 8621259 ER PT J AU Junghans, RP Stone, AL Lewis, MS AF Junghans, RP Stone, AL Lewis, MS TI Biophysical characterization of a recombinant soluble interleukin 2 receptor (Tac) - Evidence for a monomeric structure SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CIRCULAR-DICHROISM; IL-2 RECEPTOR; PROTEIN; ANTIGEN; FORM; EXPRESSION; TARGET; SYSTEM; CELLS; CORE AB The interleukin 2 receptor (IL2R) plays a prominent role in the biology of T cells, B cells, and NK cells during activation, Of the three chains described, the alpha-chain of the receptor (Tac; IL2R alpha; CD25) is the most subject to regulation and is shed from the surface of activated cells to generate a soluble form in serum and tissues, Conflicting results have been reported on the native structure of soluble Tac, suggesting variously a monomer, a dimer, or higher noncovalent forms, spawning different models for its mechanism of action, We similarly show a large M(r(app)) by HPLC sieving chromatography, suggesting a tetrameric form, However, stoichiometry-ordered size (SOS) analysis of antibody-antigen complexes indicated only a single epitope per Tac molecule, compatible with a monomeric form, This larger M(r(app)) also conflicted with prior in vivo data showing rapid filtration of soluble Tac through the renal glomerulus that was not expected of a larger complex, Using different solvents, denaturants, and columns in the chromatography suggested that the elevated M(r(app)) values were an artifact of solute column interactions, termed ''ionic exclusion,'' rather than reflecting larger native structures, Analytical ultracentrifugation using a new type of analysis specific to glycoproteins demonstrated monomeric masses under all salt conditions with no tendency to form dimers or higher aggregates, Finally, circular dichroism spectroscopy showed no salt-dependent changes to suggest conformational alterations that might correlate with mobility changes on high pressure liquid chromatography, We conclude therefore that Tac is monomeric under physiologic conditions, Assessments of higher molecular weight for the purified soluble protein by other methods may be explained by the highly acidic nature of the molecule, which hampers matrix penetration with chromatographic media and by the high carbohydrate content and low partial specific volumes that accelerate the molecule in sedimentation media relative to pure protein standards. C1 NICHHD,DEV & MOLEC IMMUN LAB,NIH,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RP Junghans, RP (reprint author), HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,BIOTHERAPEUT DEV LAB,DIV HEMATOL ONCOL,BOSTON,MA 02215, USA. NR 39 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 3 PY 1996 VL 271 IS 18 BP 10453 EP 10460 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UJ342 UT WOS:A1996UJ34200008 PM 8631840 ER PT J AU Hallenbeck, PL Minucci, S Lippoldt, P Phyillaier, M Horn, V Ozato, K Nikodem, VM AF Hallenbeck, PL Minucci, S Lippoldt, P Phyillaier, M Horn, V Ozato, K Nikodem, VM TI Differential 9-cis-retinoic acid-dependent transcriptional activation by murine retinoid X receptor alpha (RXR alpha) and RXR beta - Role of cell type and RXR domains SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID THYROID-HORMONE; DIRECT REPEAT; DNA-BINDING; GENE; RAR; HETERODIMERIZATION; PROTEIN AB The 9-cis-retinoic acid (9cRA)-inducible enhancer of the rat cellular retinol-binding protein type II gene (CRBP II) was shown to be differentially regulated by the murine retinoid X receptor alpha (RXR alpha) as compared with RXR beta. Transient transfection assays performed in NIH 3T3 fibroblast cells demonstrated that RXR alpha yielded a high level of 9cRA-dependent transcription of a reporter gene linked to the CRBP II enhancer, when compared with RXR beta. This effect was cell type-dependent, since both receptors elicited comparable transcriptional activation of the same reporter in P19 embryonal carcinoma cells, To further explore the structural determinants responsible for the differences between these two receptors, a series of chimeric receptor constructs mere made, Co-transfection assays utilizing these chimeras demonstrated that both the N terminus and the hinge region connecting the DNA binding domain with the ligand binding domain of RXR alpha were responsible for the high level of 9cRA-dependent transcription observed in MH 3T3 cells, Furthermore, the hinge region of RXR alpha was shown to be necessary to repress, in the absence of hormone, the transcriptional activation function located in the N-terminal domain of RXR alpha. These results stress the importance of functional links between different RXR domains and suggest an RXR subtype and cell type dependent specificity in the control of the 9cRA response. C1 NIDDK,GENET & BIOCHEM BRANCH,BETHESDA,MD 20892. NICHHD,LAB MOL GROWTH REGULAT,NIH,BETHESDA,MD 20892. DEPT VET AFFAIRS MED CTR,ORAL PATHOL RES LAB,WASHINGTON,DC 20422. RI Minucci, Saverio/J-9669-2012 NR 25 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 3 PY 1996 VL 271 IS 18 BP 10503 EP 10507 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UJ342 UT WOS:A1996UJ34200015 PM 8631847 ER PT J AU Ridky, TW BizubBender, D Cameron, CE Weber, IT Wlodawer, A Copeland, T Skalka, AM Leis, J AF Ridky, TW BizubBender, D Cameron, CE Weber, IT Wlodawer, A Copeland, T Skalka, AM Leis, J TI Programming the rous sarcoma virus protease to cleave new substrate sequences SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article AB The Rous sarcoma virus protease displays a high degree of specificity and catalyzes the cleavage of only a limited number of amino acid sequences. This specificity is governed by interactions between side chains of eight substrate amino acids and eight corresponding subsite pockets within the homodimeric enzyme, We have examined these complex interactions in order to learn how to introduce changes into the retroviral protease (PR) that direct it to cleave new substrates. Mutant enzymes with altered substrate specificity and wild-type or greater catalytic rates have been constructed previously by substituting single key amino acids in each of the eight enzyme subsites with those residues found in structurally related positions of human immunodeficiency virus (HIV)-1 PR. These individual amino acid substitutions have now been combined into one enzyme, resulting in a highly active mutant Rous sarcoma virus (RSV) protease that displays many characteristics associated with the HIV-1 enzyme, The hybrid protease is capable of catalyzing the cleavage of a set of HIV-1 viral polyprotein substrates that are not recognized by the wild-type RSV enzyme. Additionally, the modified PR is inhibited completely by the HIV-1 PR-specific inhibitor KNI-272 at concentrations where wild-type RSV PR is unaffected, These results indicate that the major determinants that dictate RSV and HIV-1 PR substrate specificity have been identified, Since the viral protease is a homodimer, the rational design of enzymes with altered specificity also requires a thorough understanding of the importance of enzyme symmetry in substrate selection, We demonstrate here that the enzyme homodimer acts symmetrically in substrate selection with each enzyme subunit being capable of recognizing both halves of a peptide substrate equally. C1 CASE WESTERN RESERVE UNIV,SCH MED,DEPT BIOCHEM,CLEVELAND,OH 44106. FOX CHASE CANC CTR,INST CANC RES,PHILADELPHIA,PA 19111. THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,PHILADELPHIA,PA 19107. NCI,FREDERICK CANC RES & DEV CTR,MACROMOL STRUCT LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [CA58166, CA06937, CA52047] NR 15 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 3 PY 1996 VL 271 IS 18 BP 10538 EP 10544 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UJ342 UT WOS:A1996UJ34200021 PM 8631853 ER PT J AU Lin, JX Mietz, J Modi, WS John, S Leonard, WJ AF Lin, JX Mietz, J Modi, WS John, S Leonard, WJ TI Cloning of human Stat5B - Reconstitution of interleukin-2-induced Stat5A and Stat5B DNA binding activity in COS-7 cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR GAMMA-CHAIN; IL-2 RECEPTOR; FUNCTIONAL COMPONENT; LINE; GENE AB We have isolated a second human Stat5 cDNA, Stat5B, and demonstrated that the genes encoding both Stat5A and Stat5B are located at chromosome 17q11.2, Both genes were constitutively transcribed in peripheral blood lymphocytes. By using specific antisera, we demonstrated that both Stat5A and Stat5B are activated by interleukin-2 (IL-2) in peripheral blood lymphocytes, natural killer-like YT leukemia cells, and human T cell lymphotropic virus type I-transformed MT-2 T cells. In COS-7 cells, which constitutively express the Janus family tyrosine kinase Jak1, reconstitution of IL-2-induced Stat5A and Stat5B DNA binding activities was dependent on the coexpression of Jak3 along with the IL-2 receptor beta chain and the common cytokine receptor gamma-chain. This IL-2-induced Stat5 activation was dependent on the presence of either of two tyrosines (Tyr-392 or Tyr-510) in the IL-2 receptor beta chain, indicating that either of these two tyrosines can serve as a docking site, Moreover, we demonstrated that human Stat5 activation is also dependent on Tyr-694 in Stat5A and Tyr-699 in Stat5B, indicating that these tyrosines are required for dimerization. The COS-7 reconstitution system described herein provides a valuable assay for further elucidation of the IL-2-activated JAK-STAT pathway. C1 NHLBI,LAB MOL IMMUNOL,NIH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NR 51 TC 167 Z9 169 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 3 PY 1996 VL 271 IS 18 BP 10738 EP 10744 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UJ342 UT WOS:A1996UJ34200051 PM 8631883 ER PT J AU Zhou, J Mulshine, JL Unsworth, EJ Scott, FR Avis, IM Vos, MD Treston, AM AF Zhou, J Mulshine, JL Unsworth, EJ Scott, FR Avis, IM Vos, MD Treston, AM TI Purification and characterization of a protein that permits early detection of lung cancer - Identification of heterogeneous nuclear ribonucleoprotein-A2/B1 as the antigen for monoclonal antibody 703D4 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA-BINDING-PROTEINS; GENE-EXPRESSION; SEQUENCE; SENSITIVITY; CELLS AB We have reported that a mouse monoclonal antibody, 703D4, detects lung cancer 2 years earlier than routine chest x-ray or cytomorphology, We purified the 703D4 antigen to elucidate its role in early lung cancer biology, using Western blot detection after SDS-polyacrylamide gel electrophoresis. Purification steps included anion exchange chromatography, preparative isoelectric focusing, polymer-based C-18-like, and analytical C-4 reverse phase high performance liquid chromatography. After 25-50,000-fold purification, the principal immunostaining protein was >95% pure by Coomassie staining, The NH2 terminus was blocked, so CNBr digestion was used to generate internal peptides, Three sequences, including one across a site of alternate exon splicing, all identified a single protein, heterogeneous nuclear ribonucleoprotein-A2 (hnRNP-A2), A minor co-purifying immunoreactive protein resolved at the final C-4 high performance liquid chromatography step is the splice variant hnRNP-B1, Northern analysis of RNA from primary normal bronchial epithelial cells demonstrated a low level of hnRNP-A2/B1 expression, consistent with immunohistochemical staining of clinical samples, and increased hnRNP-A2/B1 expression was found in lung cancer cells, hnRNP-A2/B1 expression is under proliferation-dependent control in normal bronchial epithelial cell primary cultures, but not in SV40-transformed bronchial epithelial cells or tumor cell lines, With our clinical data, this information suggests that hnRNP-A2/B1 is an early marker of lung epithelial transformation and carcinogenesis. C1 NCI,BIOMARKERS & PREVENT RES BRANCH,DCS,ROCKVILLE,MD 20850. NR 32 TC 106 Z9 117 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 3 PY 1996 VL 271 IS 18 BP 10760 EP 10766 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UJ342 UT WOS:A1996UJ34200054 PM 8631886 ER PT J AU Bruck, I Woodgate, R McEntee, K Goodman, MF AF Bruck, I Woodgate, R McEntee, K Goodman, MF TI Purification of a soluble UmuD'C complex from Escherichia coli - Cooperative binding of UmuD'C to single-stranded DNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECA PROTEIN; SOS MUTAGENESIS; POLYMERASE-III; CLEAVAGE; REPAIR; UMUC; GENE; UV; LEXA; OVERPRODUCTION AB The Escherichia coli UmuD' and UmuC proteins play essential roles in SOS-induced mutagenesis, Previous studies investigating the molecular mechanisms of mutagenesis have been hindered by the lack of availability of a soluble UmuC protein, We report the extensive purification of a soluble UmuD'C complex and its interactions with DNA, The molecular mass of the complex is estimated to be 70 kDa, suggesting that the complex consists of one UmuC (46 kDa) and two UmuD' (12 kDa) molecules, In contrast to its inability to bind to double-stranded DNA, UmuD'C binds cooperatively to single-stranded DNA as measured by agarose gel electrophoresis and confirmed by steady-state fluorescence depolarization, A Hill coefficient, n = 3, characterizes the binding of UmuD'C to M13 DNA and to a 600 nucleotide DNA oligomer, suggesting that at least three protein complexes may interact cooperatively when binding to DNA, The apparent equilibrium binding constant of UmuD'C to single-stranded DNA is approximately 300 nM. Binding of the complex to a short, 80 nucleotide, DNA oligonucleotide was detectable by fluorescence depolarization, but it did not appear to be cooperative, Binding of UmuD'C to single stranded M13 DNA causes an acceleration of the protein-DNA complex, suggesting that the longer DNA may undergo compaction, The UmuD'C complex associates with RecA-coated DNA, and the UmuD'C complex remains bound to DNA in the presence of RecA. C1 NIH, SECT DNA REPLIACT REPAIR & MUTAGENESIS, BETHESDA, MD 20892 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT BIOL CHEM, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, SCH MED, INST MOLEC BIOL, LOS ANGELES, CA 90024 USA. RP UNIV SO CALIF, DEPT BIOL SCI, HEDCO MOL BIOL LABS, LOS ANGELES, CA 90089 USA. FU NIA NIH HHS [AG11398]; NIGMS NIH HHS [GM42554, GM21422] NR 47 TC 84 Z9 84 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 3 PY 1996 VL 271 IS 18 BP 10767 EP 10774 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UJ342 UT WOS:A1996UJ34200055 PM 8631887 ER PT J AU Baier, LJ Bogardus, C Sacchettini, JC AF Baier, LJ Bogardus, C Sacchettini, JC TI A polymorphism in the human intestinal fatty acid binding protein alters fatty acid transport across Caco-2 cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LINE CACO-2; DIFFERENTIATION; METABOLISM; INSULIN; GLUCOSE; EXPRESSION AB The human intestinal fatty acid binding protein (IFABP) binds long-chain fatty acids in vitro, but its intracellular function has remained speculative. A poly morphism in the gene that encodes IFABP results in an alanine (Ala(54)) to threonine (Thr(54)) substitution at codon 54 that alters the in vitro binding affinity of the protein for long-chain fatty acids. To identify potential functional variability between Ala(54) and Thr(54) IFABP, we established permanently transfected Caco-2 cell lines that express either Ala(54) or Thr(54) IFABP. We found that Caco-2 cells expressing Thr(54) IFABP transport long-chain fatty acids and secrete triglycerides to a greater degree than Caco-2 cells expressing Ala(54) IFABP. These results provide the first demonstration that IFABP participates in the intracellular transport of long-chain fatty acids. In addition, the observed increase in transport of fatty acids across cells expressing Thr(54) IFABP suggests a plausible physiologic mechanism for our prior observation that Pima Indians with a Thr(54) IFABP genotype have increased post-absorptive lipid oxidation rates and are more insulin-resistant than Pimas with a Ala(54) IFABP genotype. C1 YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT BIOCHEM,BRONX,NY 10461. RP Baier, LJ (reprint author), NIDDK,NATL INST HLTH,4212 N 16TH ST,PHOENIX,AZ 85016, USA. NR 27 TC 134 Z9 139 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 3 PY 1996 VL 271 IS 18 BP 10892 EP 10896 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UJ342 UT WOS:A1996UJ34200073 PM 8631905 ER PT J AU DeNichilo, MO Yamada, KM AF DeNichilo, MO Yamada, KM TI Integrin alpha(v)beta(5)-dependent serine phosphorylation of paxillin in cultured human macrophages adherent to vitronectin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE KINASE; CELL-ADHESION; EXTRACELLULAR-MATRIX; SIGNAL TRANSDUCTION; FOCAL ADHESIONS; FIBRONECTIN; EXPRESSION; FIBROBLASTS; MODULATION; PP125(FAK) AB The macrophage colony-stimulating factor (M-CSF) is able tct induce the expression of the alpha(v) beta(5) integrin receptor on the surface of cultured human macrophages (De Nichilo, M. O., and Burns, G. F. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 2517-2521). In the present study, we establish that the adhesion of M-CSF-treated macrophages to vitronectin is mediated by the integrin alpha(v) beta(5), and show by indirect immunofluorescence analysis that alpha(v) beta(5) and the cytoskeletal protein paxillin localize to focal contacts upon adhesion to vitronectin. Immunoprecipitation and Western blot analysis revealed that M-CSF-treated macrophages do not express focal adhesion kinase (FAK), thereby providing direct evidence for integrin dependent localization of paxillin to focal contacts in the absence of FAK expression. Investigation of paxillin phosphorylation by two dimensional phosphoamino acid analysis indicates that paxillin is 99% phosphorylated on serine residue(s) in response to vitronectin adhesion, and only 1% phosphorylated on tyrosine. Stimulation of protein kinase C (PKC) activity with the phorbol ester phorbol 12-myristate 13-acetate enhances paxillin phosphorylation, while two selective inhibitors of PKC, GF109203X and chelerythrine chloride, effectively block the phosphorylation of paxillin induced in response to vitronectin adhesion. Taken together, these data demonstrate that in M-CSF-treated macrophages adherent to vitronectin, paxillin localizes to focal contacts in the absence of FAK expression and is predominantly phosphorylated on serine residue(s) in a PKC-dependent manner. RP DeNichilo, MO (reprint author), NIDR,DEV BIOL LAB,NIH,BLDG 30,RM 404,30 CONVENT DR MSC 4370,BETHESDA,MD 20892, USA. NR 47 TC 99 Z9 99 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 3 PY 1996 VL 271 IS 18 BP 11016 EP 11022 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UJ342 UT WOS:A1996UJ34200091 PM 8631923 ER PT J AU Weisz, A Scher, AL Ito, Y AF Weisz, A Scher, AL Ito, Y TI Isolation of 4'-bromo-4,5,6,7-tetrachlorofluorescein from a synthetic mixture by pH-zone-refining counter-current chromatography with continuous pH monitoring SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE counter-current chromatography; preparative chromatography; color additives; bromotetrachlorofluorescein AB A synthetic mixture containing mainly 4'-bromo-4,5,6,7-tetrachlorofluorescein (4'BrTCF, ca. 25% by high-performance liquid chromatography) was prepared by direct bromination of tetrachlorofluorescein in ethanol. The 4'BrTCF was isolated and purified by pH-zone-refining counter-current chromatography (CCC), using two different two-phase solvent systems: diethyl ether-acetonitrile-water (4:1:5, v/v) and tert.-butyl methyl ether-water (1:1, v/v). For each system, the upper organic phase was acidified and used as the stationary phase and the lower aqueous phase was made basic and used as the mobile phase. pH-Zone-refining CCC of two 5-g batches of the crude mixture yielded 1.65 g of 4'BrTCF that was ca. 95% pure by HPLC. For these separations, a commercial counter-current chromatograph was fitted with a pH electrode in a flow cell to record the pH of the effluent 'on-line,' thereby replacing the tedious and time-consuming manual measurement of the pH of each fraction. Additionally, UV spectra of the effluent were continuously monitored and stored by using a computerized scanning UV-Vis detector equipped with an adjustable short-pathlength flow cell. C1 US FDA,OFF COSMET & COLORS,WASHINGTON,DC 20204. NHLBI,BIOPHYS CHEM LAB,NIH,BETHESDA,MD 20892. NR 7 TC 30 Z9 30 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD MAY 3 PY 1996 VL 732 IS 2 BP 283 EP 290 DI 10.1016/0021-9673(95)01266-4 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA UL386 UT WOS:A1996UL38600012 PM 8653202 ER PT J AU Levy, DD Magee, AD Seidman, MM AF Levy, DD Magee, AD Seidman, MM TI Single nucleotide positions have proximal and distal influence on UV mutation hotspots and coldspots SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE sequence context; UV mutation; hotspots ID SHUTTLE VECTOR PLASMID; ESCHERICHIA-COLI; XERODERMA-PIGMENTOSUM; SEQUENCE SPECIFICITY; POINT MUTATIONS; DNA; MUTAGENESIS; CELLS; INVITRO; MISALIGNMENT AB Base substitution mutation frequency is influenced by the sequence context surrounding lesions in the DNA. We have been studying ultraviolet mutagenesis in human repair-deficient cells in the supF marker gene carried in a shuttle vector plasmid. There are prominent hotspots, on opposite strands, at the 5' TC sites in the eight base palindrome 5' CTTCGAAG. Recently, we developed a reporter system which permits sequence manipulation in the vicinity of mutational hotspots. We have used the system to characterize the influence of individual positions in the palindrome on the frequency of mutagenesis at the two UV hotspots. In this paper we have determined the contribution of bases at the second and third positions in the palindrome. Changes in bases that were in the primer template duplex when the replication complex encountered the photoproducts at one of the hotspot sites significantly increased or decreased the probability of mutations at the site. We also observed modulation of hotspot activity at other sites as a function of single base changes as much as 80 bases away from the hotspots. In these instances, the site of the changed base was in the unreplicated template ahead of the primer terminus when the polymerase encountered the relevant photoproduct. Our results indicate that sequence context has both proximal and distal consequences for mutagenesis. (C) 1996 Academic Press Limited C1 NCI,NIH,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. ONCORPHARM,GAITHERSBURG,MD 20877. NR 43 TC 16 Z9 16 U1 2 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAY 3 PY 1996 VL 258 IS 2 BP 251 EP 260 DI 10.1006/jmbi.1996.0247 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UH330 UT WOS:A1996UH33000004 PM 8627623 ER PT J AU Dyer, KD Rosenberg, HF AF Dyer, KD Rosenberg, HF TI Eosinophil Charcot-Leyden crystal protein binds to beta-galactoside sugars SO LIFE SCIENCES LA English DT Article DE eosinophil; Charcot-Leyden crystal protein; beta-galactoside sugars ID MOLECULAR-CLONING; ANIMAL LECTIN; SELECTIVE EXPRESSION; ESCHERICHIA-COLI; MUSCLE LECTIN; EPSILON-BP; MAST-CELLS; LACTOSE; IGE; LYSOPHOSPHOLIPASE AB The Charcot-Leyden crystal protein (CLC) found in human eosinophils and basophils has 43-48% amino acid sequence similarity to the galectin family of beta-galactoside binding proteins. We show here that enzymatically active recombinant CLC binds to a lactose-conjugated agarose resin, and that binding is inhibited in a dose dependent fashion by both lactose (IC50 = 41 mM) and fucose (IC50 = 380 mM), but not by arabinose. These results demonstrate that CLC has functional as well as structural homology to the galectins, and suggest that CLC may also participate, as do the galectins, in mediating cell-cell and cell-matrix interactions, and in activating the cellular immune response. C1 NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. NR 43 TC 35 Z9 36 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD MAY 3 PY 1996 VL 58 IS 23 BP 2073 EP 2082 DI 10.1016/0024-3205(96)00201-9 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA UJ059 UT WOS:A1996UJ05900002 PM 8649192 ER PT J AU Rivolta, MN Negrini, C Wilcox, ER AF Rivolta, MN Negrini, C Wilcox, ER TI A novel zinc finger gene preferentially expressed in the retina and the organ of Corti localizes to human chromosome 12q24.3 SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE zinc finger gene; organ of Corti; retina; gene regulation ID WAARDENBURG SYNDROME; DOMAINS; PROTEINS; NUMBER; CELLS AB A cDNA encoding a novel member of the zinc finger gene family, designated zfOC1, has been cloned from the organ of Corti. This is the first transcriptional regulator cloned from this sensory epithelium. This transcript encodes a peculiar protein composed of 9 zinc finger domains and a few additional amino acids. The deduced polypeptide shares 66% amino acid similarity with MOK-2, another protein of only zinc finger motifs and preferentially expressed in transformed cell lines. Northern blot hybridization analysis reveals that zfOC1 transcripts are predominantly expressed in the retina and the organ of Corti and at lower levels in the stria vascularis, auditory nerve, tongue, cerebellum, small intestine and kidney. The human gene was mapped, using a human x hamster somatic cell hybrid panel and fluorescent in situ hybridization, to chromosome 12q24.3. Because of its relative abundance in sensorineural structures (retina and organ of Corti), this regulatory gene should be considered a candidate for hereditary disorders involving hearing and visual impairments that link to 12q24.3. C1 NIDOCD,GENET MOLEC LAB,NIH,ROCKVILLE,MD 20850. NR 22 TC 7 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD MAY 2 PY 1996 VL 1306 IS 2-3 BP 127 EP 132 DI 10.1016/0167-4781(96)00022-X PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UM515 UT WOS:A1996UM51500003 PM 8634327 ER PT J AU Collins, FS AF Collins, FS TI Genetic screening for breast cancer - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP Collins, FS (reprint author), NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 2 PY 1996 VL 334 IS 18 BP 1201 EP 1201 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UG831 UT WOS:A1996UG83100026 ER PT J AU Roberts, CGP Meister, GE Jesdale, BM Lieberman, J Berzofsky, JA DeGroot, AS AF Roberts, CGP Meister, GE Jesdale, BM Lieberman, J Berzofsky, JA DeGroot, AS TI Prediction of HIV peptide epitopes by a novel algorithm SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID CYTOTOXIC LYMPHOCYTES-T; IMMUNODEFICIENCY-VIRUS TYPE-1; B-CELL EPITOPES; MHC CLASS-II; SEROPOSITIVE INDIVIDUALS; NEF PROTEIN; REVERSE-TRANSCRIPTASE; SYNTHETIC PEPTIDES; FINE SPECIFICITY; ENVELOPE PROTEIN AB Identification of promiscuous or multideterminant T cell epitopes is essential for HIV vaccine development, however, current methods for T cell epitope identification are both cost intensive and labor intensive, We have developed a computer-driven algorithm, named EpiMer, which searches protein amino acid sequences for putative MHC class I- and/or class II-restricted T cell epitopes. This algorithm identifies peptides that contain multiple MHC-binding motifs from protein sequences, To evaluate the predictive power of EpiMer, the amino acid sequences of the HIV-1 proteins nef, gp160, gag p55, and tat were searched for regions of MHC-binding motif clustering, We assessed the algorithm's predictive power by comparing the EpiMer-predicted peptide epitopes to T cell epitopes that have been published in the literature, The EpiMer method of T cell epitope identification was compared to the standard method of synthesizing short, overlapping peptides and testing them for immunogenicity (overlapping peptide method), and to an alternate algorithm that has been used to identify putative T cell epitopes from primary structure (AMPHI). For the four HIV-1 proteins analyzed, the in vitro testing of EpiMer peptides for immunogenicity would have required the synthesis of fewer total peptides than either AMPHI or the overlapping peptide method, The EpiMer algorithm proved to be more efficient and more sensitive per amino acid than both the overlapping peptide method and AMPHI, The EpiMer predictions for these four HIV proteins are described, Since EpiMer-predicted peptides have the potential to bind to multiple MHC alleles, they are strong candidates for inclusion in a synthetic HIV vaccine. C1 BROWN UNIV,SCH MED,DIV BIOL & MED,TB HIV RES LAB,PROVIDENCE,RI 02912. HARVARD UNIV,MED CTR,CTR BLOOD RES,BOSTON,MA 02112. NCI,MOLEC IMMUNOGENET & VACCINE RES SECT,METAB BRANCH,NIH,BETHESDA,MD 20892. MIRIAM HOSP,DEPT GEOG MED & CLIN IMMUNOL,PROVIDENCE,RI 02906. RI De Groot, Anne/B-6221-2013; Lieberman, Judy/A-2717-2015 OI De Groot, Anne/0000-0001-5911-1459; FU NCI NIH HHS [R08 CA01449]; NIAID NIH HHS [R01 AI35271, U19 AI36611] NR 86 TC 31 Z9 31 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY 1 PY 1996 VL 12 IS 7 BP 593 EP 610 DI 10.1089/aid.1996.12.593 PG 18 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA UF722 UT WOS:A1996UF72200006 PM 8743085 ER PT J AU Switzer, WM Black, FL Pieniazek, D Biggar, RJ Lal, RB Heneine, W AF Switzer, WM Black, FL Pieniazek, D Biggar, RJ Lal, RB Heneine, W TI Endemicity and phylogeny of the human T cell lymphotropic virus type II subtype a from the Kayapo Indians of Brazil: Evidence for limited regional dissemination SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article AB Long terminal repeat (LTR)-based restriction fragment length polymorphism (RFLP) analysis of human T cell lymphotropic virus type II (HTLV-II) from 17 seropositive Kayapo Indians from Brazil showed that all 17 samples contained a unique HTLV-IIa subtype (A-II). Additional RFLP screening demonstrated the presence of this subtype in two of three Brazilian blood donors and a Mexican prostitute and her child. In contrast, 129 samples from blood donors and intravenous drug users (IDUs) from the United States, two Pueblo Indian samples, five samples from Norwegian IDUs, and two samples from blood donors from Denmark were all found to be a different HTLV-IIa subtype (A-III), Phylogenetic analysis of two Kayapo and one Mexican LTR sequences showed that they cluster with a subtype A-II sequence from a Brazilian blood donor and with sequences from two prostitutes from Ghana and Cameroon, These results demonstrate that infection with the A-LI subtype is endemic among the Kayapo Amerindians, has disseminated to non-Indian populations in Brazil, and is also present in Mexico, Furthermore, the A-II subtype does not appear to represent an origin for the HTLV-IIa infection in urban areas of the United States and Europe, This study provides evidence that HTLV-IIa may be a Paleo-Indian subtype as previously suggested for HTLV-IIb. C1 CTR DIS CONTROL & PREVENT,RETROVIRUS DIS BRANCH,DIV AIDS SEXUALLY TRUNSMITTED DIS & TB LAB RES,ATLANTA,GA 30333. YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06520. CTR DIS CONTROL & PREVENT,DIV HIV AIDS,NATL CTR INFECT DIS,ATLANTA,GA 30333. NCI,VIRAL EPIDEMIOL BRANCH,ROCKVILLE,MD 20850. NR 18 TC 37 Z9 41 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY 1 PY 1996 VL 12 IS 7 BP 635 EP 640 DI 10.1089/aid.1996.12.635 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA UF722 UT WOS:A1996UF72200010 PM 8743089 ER PT J AU Cohen, SG AF Cohen, SG TI Asthma among the famous - A continuing series SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article RP Cohen, SG (reprint author), NIAID,BETHESDA,MD 20892, USA. NR 26 TC 1 Z9 1 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD MAY-JUN PY 1996 VL 17 IS 3 BP 161 EP 172 DI 10.2500/108854196779165030 PG 12 WC Allergy SC Allergy GA UQ493 UT WOS:A1996UQ49300006 ER PT J AU Goldstein, AM Goldin, LR Dracopoli, NC Clark, WH Tucker, MA AF Goldstein, AM Goldin, LR Dracopoli, NC Clark, WH Tucker, MA TI Two-locus linkage analysis of cutaneous malignant melanoma/dysplastic nevi SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID MELANOMA DYSPLASTIC NEVUS; FAMILIAL MELANOMA; CHROMOSOME-1P; EXCLUSION; PEDIGREES; MLM; ARM AB Previous linkage analyses of 19 cutaneous malignant melanoma/dysplastic nevi (CMM/DN) kindreds showed significant evidence of linkage and heterogeneity to both chromosomes 1p and 9p, Five kindreds also showed evidence of linkage (Z > 0.7) to both regions. To further examine these findings, we conducted two-trait-locus, two-marker-locus linkage analysis. We examined one homogeneity and one heterogeneity single-locus model (SL-Hom and SL-Het), and two two-locus (2L) models: an epistatic model (Ep), in which CMM was treated as a genuine 2L disease, and a heterogeneity model (Het), in which CMM could result from disease alleles at either locus. Both loci were modeled as autosomal dominant, The LOD scores for CMM alone were highest using the SL-Het model (Z = 8.48, theta = .0). There was much stronger evidence of linkage to chromosome 9p than to 1p for CMM alone; the LOD scores were approximately two times greater on 9p than on 1p. The change in LOD scores from an evaluation of CMM atone to CMM/DN suggested that a chromosome 1p locus (or loci) contributed to both CMM and CMM/DN, whereas a 9p locus contributed more to CMM alone. For both 2L models, the LOD scores from 1p were greater for CMM/DN than for CMM alone (Ep: Z = 4.63 vs. 3.83; Het: 4.94 vs. 3.80, respectively). In contrast, for 9p, the LOD scores were substantially lower with CMM/DN than with CMM alone (Ep: 4.64 vs. 7.06; Het: 5.38 vs. 7.99, respectively). After conditioning on linkage to the other locus, only the 9p locus consistently showed significant evidence for linkage to CMM alone. Thus, the application of 2L models may be useful to help unravel the complexities of familial melanoma. C1 NIMH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. SEQUANA THERAPEUT INC,LA JOLLA,CA. UNIV PENN,SCH MED,PIGMENTED LESION STUDY GRP,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT DERMATOL,PHILADELPHIA,PA 19104. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT PATHOL,BOSTON,MA. RP Goldstein, AM (reprint author), NCI,GENET EPIDEMIOL BRANCH,EXECUT PLAZA N,ROOM 439,6130 EXECUT BLVD MSC 7372,BETHESDA,MD 20892, USA. RI Tucker, Margaret/B-4297-2015 NR 35 TC 40 Z9 40 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY PY 1996 VL 58 IS 5 BP 1050 EP 1056 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA UH192 UT WOS:A1996UH19200018 PM 8651266 ER PT J AU Levey, AS Adler, S Caggiula, AW England, BK Greene, T Hunsicker, LG Kusek, JW Rogers, NL Teschan, PE AF Levey, AS Adler, S Caggiula, AW England, BK Greene, T Hunsicker, LG Kusek, JW Rogers, NL Teschan, PE TI Effects of dietary protein restriction on the progression of advanced renal disease in the modification of diet in renal disease study SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE renal disease; progression; dietary protein; glomerular filtration rate ID AMINO-ACID SUPPLEMENT; FAILURE; NITROGEN; TRIAL; INSUFFICIENCY; REDUCTION; KETOACIDS AB Patients with advanced renal disease randomized to the very low-protein diet group in the Modification of Diet in Renal Disease (MDRD) Study had a marginally (P = 0.066) slower mean glomerular filtration rate (GFR) decline compared with patients randomized to the low-protein diet group, The objective of these secondary analyses was to determine the relationship between achieved, in addition to prescribed, dietary protein intake and the progression of advanced renal disease, A randomized controlled trial was conducted in patients with chronic renal diseases of diverse etiology, The average follow-up was 2.2 years, Fifteen university hospital outpatient nephrology practices participated in the study, which comprised 255 patients aged 18 to 70 years with a baseline GFR 13 to 24 mL/min/1.73 m(2) who participated in MDRD Study B. Patients with diabetes requiring insulin were excluded, The patients were given a low-protein (0.58 g/kg/d) or very low-protein (0.28 g/kg/d) diet supplemented with keto acids-amino acids (0.28 g/kg/d), Outcomes were measured by comparisons of protein intake from food or from food and supplement between randomized groups, and correlations of protein intake with rate of decline in GFR and time to renal failure or death, Comparison of the randomized groups showed that total protein intake from food and supplement was lower (P < 0.001) among patients randomized to the very low-protein diet (0.66 g/kg/d) compared with protein intake from food only in patients randomized to the low-protein diet (0.73 g/kg/d), In correlational analyses, we combined patients assigned to both diets and controlled for baseline factors associated with a faster progression of renal disease, A 0.2 g/kg/d lower achieved total protein intake (including food and supplement) was associated with a 1.15 mL/min/yr slower mean decline in GFR (P = 0.011), equivalent to 29% of the mean GFR decline, After adjusting for achieved total protein intake, no independent effect of prescription of the keto acid-amino acid supplement to slow the GFR decline could be detected, If the GFR decline is extrapolated until renal failure, a patient with a 29% reduction in the rate of GFR decline would experience a 41% prolongation in the time to renal failure, Additional analyses confirmed a longer time to renal failure in patients with lower total protein intake. In conclusion, these secondary analyses of the MDRD Study suggest that a lower protein intake, but not the keto acid-amino acid supplement, retards the progression of advanced renal disease, In patients with GFR less than 25 mL/min/1.73 m(2), we suggest a prescribed dietary protein intake of 0.6 g/kg/d. (C) 1996 by the National Kidney Foundation, Inc. C1 NIDDKD,NIH,BETHESDA,MD 20892. NR 40 TC 206 Z9 216 U1 0 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAY PY 1996 VL 27 IS 5 BP 652 EP 663 DI 10.1016/S0272-6386(96)90099-2 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA UJ497 UT WOS:A1996UJ49700006 PM 8629624 ER PT J AU Yoon, BH Romero, R Yang, SH Jun, JK Kim, IO Choi, JH Syn, HC AF Yoon, BH Romero, R Yang, SH Jun, JK Kim, IO Choi, JH Syn, HC TI Interleukin-6 concentrations in umbilical cord plasma are elevated in neonates with white matter lesions associated with periventricular leukomalacia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE periventricular leukomalacia; interleukin-6; cytokines; umbilical cord ID TUMOR-NECROSIS-FACTOR; PRETERM INFANTS; INTRAVENTRICULAR HEMORRHAGE; CEREBRAL-PALSY; ULTRASOUND; LEUCOMALACIA; DAMAGE; COAGULATION; ENDOTOXIN; NEWBORN AB OBJECTIVE: Periventricular leukomalacia, a common brain white matter lesion in preterm neonates, is a major risk factor for cerebral palsy. Recently, cytokines (i.e., tumor necrosis factor and interleukin-1 beta) have been implicated as mediators for the development of periventricular leukomalacia. The purpose of this study was to examine the relationship between umbilical cord plasma levels of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, and interleukin-1 receptor antagonist and the occurrence of periventricular leukomalacia in preterm neonates. STUDY DESIGN: Umbilical cord blood was collected from 172 consecutive preterm births (25 to 36 weeks). Periventricular leukomalacia-associated lesions were diagnosed by brain ultrasonography within the first 3 days of life. Tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, and interleukin-1 receptor antagonist were measured by sensitive and specific enzyme-linked immunoassay methods. Umbilical cord arterial pH was measured at birth. Statistical analysis was performed with multiple logistic regression and receiver operating characteristic curve analysis. RESULTS: Periventricular leukomalacia-associated lesions were present in 14.5% (25/172) of infants. Plasma concentrations of interleukin-6 but not of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-1 receptor antagonist were significantly higher in neonates with periventricular leukomalacia-associated lesions than in those without these lesions (median 718, range <226 to 32,000 pg/ml vs median <226, range <226 to 43,670 pg/ml; p < 0.0001). An interleukin-6 value greater than or equal to 400 pg/ml had a sensitivity of 72% (18/25) and a specificity of 74% (108/147) in the identification of periventricular leukomalacia-associated lesions. Multivariate analysis showed that umbilical cord interleukin-6 was an independent risk factor for periventricular leukomalacia (odds ratio 6.2, p < 0.002) after correction for known confounding variables (i.e., gestational age at birth, umbilical artery pH, chorioamnionitis). CONCLUSIONS: Interleukin-6 concentrations in umbilical cord plasma are elevated in neonates with periventricular leukomalacia-associated lesions. Our data support the hypothesis that periventricular leukomalacia may be the result of cytokine-mediated brain injury. C1 SEOUL NATL UNIV,DEPT RADIOL,COLL MED,SEOUL 110744,SOUTH KOREA. SEOUL NATL UNIV,DEPT PEDIAT,COLL MED,SEOUL 110744,SOUTH KOREA. NICHHD,PERINATOL BRANCH,BETHESDA,MD 20892. RP Yoon, BH (reprint author), SEOUL NATL UNIV,DEPT OBSTET & GYNECOL,COLL MED,SEOUL 110744,SOUTH KOREA. RI Yoon, Bo Hyun/H-6344-2011; Kim, In-One/J-5427-2012; Jun, Jong Kwan/D-5776-2012 OI Jun, Jong Kwan/0000-0002-0242-1736 NR 32 TC 380 Z9 387 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAY PY 1996 VL 174 IS 5 BP 1433 EP 1440 DI 10.1016/S0002-9378(96)70585-9 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA UQ173 UT WOS:A1996UQ17300007 PM 9065108 ER PT J AU Burns, DN Noujah, P Minkoff, H Korelitz, J Biggar, RJ Landesman, S Rubinstein, A Wright, D Nugent, RP AF Burns, DN Noujah, P Minkoff, H Korelitz, J Biggar, RJ Landesman, S Rubinstein, A Wright, D Nugent, RP TI Changes in CD4(+) and CD8(+) cell levels during pregnancy and post partum in women seropositive and seronegative for human immunodeficiency virus-1 SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE pregnancy; T lymphocytes; human immunodeficiency virus; acquired immunodeficiency syndrome; immunity ID DECREASED LEVELS; LYMPHOCYTES-T; INFECTION; IMMUNITY; COUNT; CD4+ AB OBJECTIVE: Our objective was to examine changes in CD4(+) and CD8(+) cell levels during pregnancy and post partum and to determine whether they differ for human immunodeficiency virus-l-seropositive and seronegative women. STUDY DESIGN: A total of 192 human immunodeficiency virus-1-seropositive and 148 seronegative women enrolled in a study of mother-to-child transmission of human immunodeficiency virus-1 who had at least two lymphocyte subset measurements performed during pregnancy or post partum were included in this analysis. Mixed effects repeated-measures models were developed to examine changes in CD4(+) and CD8(+) cell levels during this period. RESULTS: Consistent with prior reports that CD4(+) cell levels decline during pregnancy and return to normal post partum, percent levels increased between the third trimester and 12 months post partum among human immunodeficiency virus-seronegative women (1.98%, p = 0.04). However, CD4(+) levels declined steadily during pregnancy and post partum among seropositive women (-1.57%, p = 0.02 between the third trimester and 12 months post partum; -2.65%, p = 0.0004 between 2 and 24 months post partum). The percent CD8(+) cell levels increased at or near delivery and declined to baseline between 2 and 6 months post partum in both seronegative and seropositive women, although only the declines were statistically significant in both groups (-2.66%, p = 0.004; and 2.02%, p = 0.02, respectively). CONCLUSIONS: The percent CD4(+) cell levels declined steadily during pregnancy and post partum among human immunodeficiency virus-seropositive women, indicating that human immunodeficiency virus disease continues to progress during this period. The percent CD8(+) cell levels increased at or near delivery and declined to baseline post partum in both seronegative and seropositive women. These findings may have important clinical implications for both human immunodeficiency virus-infected and uninfected pregnant women. C1 NCI,VIRAL EPIDEMIOL BRANCH,NIH,BETHESDA,MD 20892. WESTAT CORP,BETHESDA,MD. SUNY HLTH SCI CTR,DEPT OBSTET & GYNECOL,BROOKLYN,NY 11203. SUNY HLTH SCI CTR,DEPT MED,BROOKLYN,NY 11203. ALBERT EINSTEIN COLL MED,DEPT PEDIAT,BRONX,NY 10467. RP Burns, DN (reprint author), NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,CTR RES MOTHERS & CHILDREN,6100 EXECUT BLVD,ROCKVILLE,MD 20892, USA. FU NCI NIH HHS [N0-1-CP-61013]; NICHD NIH HHS [N0-1-HD-8-2913, R0-1-HD-25714] NR 25 TC 33 Z9 35 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAY PY 1996 VL 174 IS 5 BP 1461 EP 1468 DI 10.1016/S0002-9378(96)70589-6 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA UQ173 UT WOS:A1996UQ17300011 PM 9065112 ER PT J AU Goldenberg, RL Klebanoff, MA Nugent, R Krohn, MA Hillier, S Andrews, WW AF Goldenberg, RL Klebanoff, MA Nugent, R Krohn, MA Hillier, S Andrews, WW TI Bacterial colonization of the vagina during pregnancy in four ethnic groups SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE vaginal flora; bacterial vaginosis; ethnic differences; gonorrhea; chlamydia ID BIRTH-WEIGHT; GRAM STAIN; INFECTION; WOMEN AB OBJECTIVE: Our purpose was determine whether there are ethnic diferences in vaginal colonization with organisms reputed to be associated with preterm delivery. STUDY DESIGN: In seven urban medical centers in the United States from 1984 to 1989, 13,747 predominantly low-socioeconomic-status women at 23 to 26 weeks' gestation were grouped according to ethnic origin. Each had a vaginal culture for multiple organisms and Gram's stain and pH test to diagnose bacterial vaginosis. Multivariate analyses with adjustment for maternal age, insurance status, marital status, smoking history, education level, age at first sexual intercourse, and number of male partners in the past year were also performed to determine the odds ratio for a black woman versus a white woman having a positive test result. RESULTS: For nearly every organism studied, Asian-Pacific Islander and white women had the lowest percentages of positive test results whereas black women had the highest. When black and white women are compared, black women were more likely to be colonized with Chlamydia trachomatis, 16% versus 5%; Neisseria gonorrhoeae, 2.5% versus 0.4%; Bacteroides sp., 25% versus 14%; bacterial vaginosis, 23% versus 9%; and the four other organisms evaluated. Adjustment for potential confounders including certain health behaviors did not markedly change the risk of a black woman having a positive test result, with the odds ratios for colonization with each organism ranging from 1.8 to 6.4. CONCLUSIONS: Highly significant differences exist in vaginal colonization patterns among women of different ethnic groups, with the highest rates of potentially pathogenic organisms observed in black women and the lowest in Asian-Pacific Islander women. Differences in health behaviors do not explain the Variation in colonization rates. C1 NICHHD,NATL INST HLTH,BETHESDA,MD. UNIV WASHINGTON,SEATTLE,WA 98195. RP Goldenberg, RL (reprint author), UNIV ALABAMA,DEPT OBSTET & GYNECOL,DIV MATERNAL FETAL MED,BIRMINGHAM,AL 35294, USA. NR 24 TC 128 Z9 129 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAY PY 1996 VL 174 IS 5 BP 1618 EP 1621 DI 10.1016/S0002-9378(96)70617-8 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA UQ173 UT WOS:A1996UQ17300039 PM 9065140 ER PT J AU Snow, JB AF Snow, JB TI News from the national institute on deafness and other communication disorders SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article RP Snow, JB (reprint author), NATL INST DEAFNESS & OTHER COMMUN DISORDERS,NIH,BLDG 31,RM 3C02,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD MAY PY 1996 VL 17 IS 3 BP 493 EP 495 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA UV040 UT WOS:A1996UV04000022 PM 8817031 ER PT J AU StetlerStevenson, WG AF StetlerStevenson, WG TI Dynamics of matrix turnover during pathologic remodeling of the extracellular matrix SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID METALLOPROTEINASES RP StetlerStevenson, WG (reprint author), NCI,NIH,DIV CLIN SCI,PATHOL LAB,EXTRACELLULAR MATRIX PATHOL SECT,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 34 TC 229 Z9 234 U1 1 U2 5 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAY PY 1996 VL 148 IS 5 BP 1345 EP 1350 PG 6 WC Pathology SC Pathology GA UJ473 UT WOS:A1996UJ47300004 PM 8623905 ER PT J AU Weaver, JL McKinney, L Schoenlein, PV Goldenberg, S Gottesman, MM Aszalos, A AF Weaver, JL McKinney, L Schoenlein, PV Goldenberg, S Gottesman, MM Aszalos, A TI MDR1/P-glycoprotein function .1. Effect of hypotonicity and inhibitors on rhodamine 123 exclusion SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE multidrug resistance; chloride channel; drug efflux; cyclosporine A; 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid; 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid; flufenamic acid ID SENSITIVE CHLORIDE CONDUCTANCE; RESISTANCE P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; CELLS; FORSKOLIN; IDENTIFICATION; TRANSPORTER; EXPRESSION; MEMBRANE; CHANNELS AB The MDR1 protein (P-glycoprotein) is a membrane ATPase whose expression results in resistance to several anti-tumor drugs. It has been proposed that the MDR1 protein, in addition to its pumplike properties, can function as (Gill et al. Cell 71: 23-32, 1992; Altenberg et al. Cancer Res. 54: 618-622, 1994) or mediate the activity of (Hardy et al. EMBO J. 14: 68-75, 1995) a hypotonic stress-induced Cl- current. In addition, one study found that drug transport and Cl- channel-associated functions of MDR1 were separable and mutually exclusive and that, when cells were swelled, the MDR1 protein could not transport substrate. This hypothesis was tested in four pairs of isogenic cell lines with MDR1 transfectants expressing 8,000-55,000 MDR1 antibody binding sites per cell. Cytoplasmic exclusion of rhodamine 123 was used as an indicator of MDR1 function to measure the effect of hypotonic stress, MDR1 inhibitors, and Cl- channel blockers on MDR1 transport function. It was found that MDR1 activity and its inhibition by cyclosporine A or flufenamic acid were unaffected by hypotonicity alone or in combination with Cl- channel blockers. C1 ARMED FORCES RADIAT RADIOBIOL INST, DEPT PHYSIOL, BETHESDA, MD 20892 USA. NCI, CELL BIOL LAB, NIH, BETHESDA, MD 20892 USA. MED COLL GEORGIA, DEPT ANAT & CELL BIOL, AUGUSTA, GA 30912 USA. RP Weaver, JL (reprint author), US FDA, CTR DRUG EVALUAT & RES,DIV RES & TESTING,MOD-1, RM 3309, 8301 MUIRKIRK RD, LAUREL, MD 20708 USA. NR 35 TC 13 Z9 13 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD MAY PY 1996 VL 270 IS 5 BP C1447 EP C1452 PG 6 WC Cell Biology; Physiology SC Cell Biology; Physiology GA UJ814 UT WOS:A1996UJ81400023 ER PT J AU Liang, Y Bai, G Doliba, N Buettger, C Wang, LQ Berner, DK Matschinsky, FM AF Liang, Y Bai, G Doliba, N Buettger, C Wang, LQ Berner, DK Matschinsky, FM TI Glucose metabolism and insulin release in mouse beta HC9 cells, as model for wild-type pancreatic beta-cells SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE beta TC3 cell; Glut-8; glucokinase ID ISLETS; SECRETION; TRANSPORTER; DEHYDROGENASE; LINE; COA AB Glucose metabolism and its relationship with glucose-induced insulin release were studied in beta HC9 and beta TC3 cells to identify and characterize key factors controlling the intermediary metabolism of glucose and glucose-induced insulin release. The beta HC9 cell line, derived from pancreatic islets with beta-cell hyperplasia, is characterized by a normal concentration-dependency curve for glucose-stimulated insulin release, whereas the beta TC3 cell line, derived from pancreatic beta-cell tumors, shows a marked leftward shift of this curve. Maximum velocity and the Michaelis-Menten constant of glucose uptake in beta HC9 and beta TC3 cells were similar, even though GLUT-2 expression in these two cell lines differed. In both cell lines, the kinetic characteristics of glucose usage, glucose oxidation, and glucose-induced oxygen consumption were similar to those of glucose phosphorylation, indicating that the kinetics of glucose metabolism from the glucose phosphorylation step in the cytosol to the mitochrondrial process of oxidative phosphorylation are determined by the glucose-phosphorylating enzyme, that is, by glucokinase in beta HC9 cells and by hexokinase in beta TC3 cells. Thus beta HC9 cells provide an opportunity for the quantitative analysis of glucose metabolism, the associated generation of coupling factors, and other essential beta-cell functions involved in glucose sensing and insulin secretion. C1 DIABET RES CTR, PHILADELPHIA, PA 19104 USA. UNIV PENN, SCH MED, DEPT BIOCHEM & BIOPHYS, PHILADELPHIA, PA 19104 USA. NIA, GERONTOL RES CTR, NIH, BALTIMORE, MD 21224 USA. FU NIDDK NIH HHS [DK-19525, DK-22122] NR 35 TC 51 Z9 51 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD MAY PY 1996 VL 270 IS 5 BP E846 EP E857 PG 12 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA UJ811 UT WOS:A1996UJ81100016 PM 8967474 ER PT J AU Tian, Y Baukal, AJ Sandberg, K Bernstein, KE Balla, T Catt, KJ AF Tian, Y Baukal, AJ Sandberg, K Bernstein, KE Balla, T Catt, KJ TI Properties of AT(1a) and AT(1b) angiotensin receptors expressed in adrenocortical Y-1 cells SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE phospholipase C; adenosine 3',5'-cyclic monophosphate; calcium ID ADRENAL GLOMERULOSA CELLS; II RECEPTOR; ADENYLATE-CYCLASE; TYPE-1 RECEPTOR; SUBTYPES; CLONING; RAT; IDENTIFICATION; INHIBITION; CDNA AB Adrenocortical Y-1 cells were stably transfected with the AT(1a) and AT(1b) subtypes of the rat angiotensin (ANG) II AT(1) receptor cDNA to study the pharmacological and functional properties of the two receptors. Selected clones of transfected cells expressing the AT(1a) or AT(1b) receptor subtypes bound the native ligand ANG II and the peptide antagonist [Sar(1),Ile(8)]ANG II with similar affinities, but they differed in their relative affinities for the nonpeptide antagonist losartan (half-maximal inhibitory concentration 9.7 and 4.7 nM), ANG III (126 and 33 nM), and the peptide antagonist [Sar(1),Gly(8)]ANG II (6.2 and 1.2 nM). Photoaffinity labeling of the expressed receptors revealed a single component of 65 kDa for both receptor subtypes, suggesting that both receptors were glycosylated in a similar manner. The sensitivity of I-125-ANG II binding to AT(1a) and AT(1b) receptors to guanine nucleotides was unaffected by pertussis toxin treatment. ANG II stimulated the formation of inositol phosphates and increased the level of cytoplasmic Ca2+ in both AT(1a)- and AT(1b)-transfected Y-1 cells. However, ANG II had little effect on forskolin-induced adenosine 3',5'-cyclic monophosphate accumulation, causing only minor inhibition in AT(1a)-transfected cells and slight enhancement in AT(1b)-transfected cells. These data indicate that AT(1a) and AT(1b) receptors show small but significant differences in their binding pharmacology and, upon activation, are coupled through G(q)G(11) to the phosphoinositide-Ca2+ signaling pathway However, neither AT(1a) nor AT(1b) receptors exhibit coupling to G(i) and inhibition of adenylate cyclase when expressed in murine adrenal tumor cells. C1 NICHHD, ERRB, NIH, BETHESDA, MD 20892 USA. EMORY UNIV, SCH MED, DEPT PATHOL, ATLANTA, GA 30322 USA. EMORY UNIV, SCH MED, DEPT MED, ATLANTA, GA 30322 USA. NR 34 TC 30 Z9 31 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD MAY PY 1996 VL 270 IS 5 BP E831 EP E839 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA UJ811 UT WOS:A1996UJ81100014 PM 8967472 ER PT J AU Yoshigi, M Hu, N Keller, BB AF Yoshigi, M Hu, N Keller, BB TI Dorsal aortic impedance in stage 24 chick embryo following acute changes in circulating blood volume SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE cardiovascular development; arterial impedance; windkessel model ID ARTERIAL INPUT IMPEDANCE; HEMODYNAMICS; PRESSURE; MODEL; TREE AB The effects of acute changes in circulating blood volume on embryonic vascular hemodynamics were evaluated with the use of input impedance. We simultaneously measured dorsal aortic pressure with a servo-null system and flow velocity with a 20-MHz pulsed Doppler system in n = 90 stage 24 chick embryos. We withdrew or infused 1, 3, or 5 mu l of blood via a second-order vitelline vein (n = 10 per group). In addition, we withdrew and then infused or infused and then withdrew 3 mu l (n = 5 per group). Characteristic impedance, peripheral resistance, arterial compliance and elastance, and hydraulic power as well as basic hemodynamic parameters were evaluated on the basis of the three-element windkessel model. In response to withdrawal, mean and pulse pressure, mean flow, arterial compliance, and hydraulic power decreased, whereas peripheral resistance and arterial elastance increased in a dose-dependent manner. Results in response to infusion were converse in effect. Characteristic impedance was unchanged by volume alterations. Oscillatory fraction of hydraulic power was higher than mature circulation and remained relatively constant during interventions, which indicates well-regulated energy efficiency for vascular growth in the embryonic circulation. A hysteresis relevant to altered peripheral resistance was present after multiple interventions. Embryonic vasculature is sensitive to circulating blood volume and preserve blood pressure at the expense of blood flow. In the absence of autonomic innervation, embryonic vascular tone may be regulated by mechanical properties of the vessel (the law of Laplace) and/or vasoactive substances. C1 UNIV ROCHESTER, SCH MED & DENT,DEPT PEDIAT, STRONG CHILDRENS RES CTR,NIH, ROCHESTER, NY 14642 USA. NR 30 TC 25 Z9 25 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAY PY 1996 VL 270 IS 5 BP H1597 EP H1606 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA UK351 UT WOS:A1996UK35100011 ER PT J AU Guzman, K Bader, T Nettesheim, P AF Guzman, K Bader, T Nettesheim, P TI Regulation of MUC5 and MUC1 gene expression: Correlation with airway mucous differentiation SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE mucin; cell differentiation; retinoic acid; trachea ID TRACHEAL EPITHELIAL-CELLS; QUANTITATIVE HISTOCHEMISTRY; MOLECULAR-CLONING; MUCINS; MUCOSUBSTANCES; CONSERVATION; ANTIBODIES; SURFACE; NASAL AB The purpose of this paper was to obtain probes to study the structure and function of mucins in rat models of airway cell differentiation and disease. We report the isolation and characterization of the rat cDNA homologue of the human airway secretory mucin, MUGS. Furthermore, we demonstrate the coordinate regulation of the expression of MUC5 and MUC1 (a membrane-bound mucin) and mucous differentiation. The rat MUC5 was cloned by the RT-PCR using motifs conserved in the secretory mucins, MUC2 and MUC5. The rat cDNA revealed a high degree of sequence similarity to human MUC5 (73% at the amino acid level). Alignments with three other secretory mucins (human MUC5, human MUC2, rat MUC2), indicated a conservation of the cysteines and of the octapeptide motifs, but a lack of conservation of a short tandem repeat sequence that is found only in the human MUC5. Northern analysis of MUC1 and MUGS indicated a specific tissue-restricted pattern of expression. Surprisingly, rat MUC5 exhibited a monodisperse signal, a characteristic that is unusual for most secretory mucins, including the human MUC5. Expression of MUC1 and MUC5 correlated with mucous differentiation. Both genes were expressed at undetectable or very low levels in undifferentiated cultures, but both mucins became strongly expressed during mucous differentiation. Furthermore, neither mucin gene was expressed in retinoid-deficient cultures that undergo squamous instead of mucous differentiation. These studies demonstrate that expression of MUC1 and MUC5 is coordinately regulated with airway mucous cell differentiation. These cDNAs should provide useful tools to study mucin synthesis during differentiation and disease. RP Guzman, K (reprint author), NIEHS, PULM PATHOBIOL LAB, POB 12233, MD D2-03, RES TRIANGLE PK, NC 27709 USA. NR 39 TC 40 Z9 40 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD MAY PY 1996 VL 270 IS 5 BP L846 EP L853 PG 8 WC Physiology; Respiratory System SC Physiology; Respiratory System GA UJ810 UT WOS:A1996UJ81000019 PM 8967520 ER PT J AU Hill, EM Bader, T Nettesheim, P Eling, TE AF Hill, EM Bader, T Nettesheim, P Eling, TE TI Retinoid-induced differentiation regulates prostaglandin H synthase and cPLA(2) expression in tracheal epithelium SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE tracheal epithelial cells; retinoic acid; phospholipase A(2); differentiation ID TUMOR-NECROSIS-FACTOR; GENE-EXPRESSION; ARACHIDONIC-ACID; CELLS; CYCLOOXYGENASE; CLONING; MARKERS AB Rat tracheal epithelial cells cultured in vitro at an air-liquid interface can differentiate into a mucociliary or squamous phenotype depending on the presence or absence of retinoic acid (RA). The airway epithelium is known to produce a number of eicosanoids. We propose that eicosanoid biosynthesis is dependent on the differentiation status of the epithelium. Therefore, prostaglandin production and the expression of cytosolic phospholipase A(2) (cPLA(2)) and the prostaglandin H synthase (PGHS) isoforms were investigated during differentiation to these two phenotypes. The major eicosanoid produced by both phenotypes was prostaglandin E(2) (PGE(2)). Proliferating undifferentiated cultures produced low levels of PGE(2) regardless of retinoid status. Differentiated mucociliary cultures produced high levels of PGE(2) (50 ng/10(6) cells), whereas differentiated squamous cultures produced low levels of PGE(2) (<5 ng/10(6) cells). Mucociliary cultures expressed high levels of cPLA(2) and PGHS-2 isoform mRNA and protein. In contrast squamous cultures expressed very low levels of cPLA(2) and PGHS-2 transcript and protein. The PGHS-1 isoform was expressed in squamous but not in mucociliary cultures. We investigated changes in expression of these enzymes during retinoid treatment of established squamous cultures. Treatment with RA resulted in a rapid (24 h) downregulation of PGHS-1 mRNA expression. However, the cPLA(2) and PGHS-2 genes were expressed in squamous cultures only after 3 days of RA treatment coincident with redifferentiation of the culture to a mucociliary phenotype. These studies reveal that retinoid-induced differentiation of airway epithelium into either a mucociliary or squamous phenotype results in profound changes in the expression of cPLA(2) and PGHS isozymes that regulate prostaglandin formation. C1 NIEHS, MOLEC BIOPHYS LAB, RES TRIANGLE PK, NC 27709 USA. NIEHS, PULM PATHOBIOL LAB, RES TRIANGLE PK, NC 27709 USA. NR 33 TC 22 Z9 22 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD MAY PY 1996 VL 270 IS 5 BP L854 EP L862 PG 9 WC Physiology; Respiratory System SC Physiology; Respiratory System GA UJ810 UT WOS:A1996UJ81000020 PM 8967521 ER PT J AU TeruyaFeldstein, J Temeck, BK Sloas, MM Kingma, DW Raffeld, M Pass, HI Mueller, B Jaffe, ES AF TeruyaFeldstein, J Temeck, BK Sloas, MM Kingma, DW Raffeld, M Pass, HI Mueller, B Jaffe, ES TI Pulmonary lymphoma in an immunocompromised host - Reply SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Letter RP TeruyaFeldstein, J (reprint author), NCI,BETHESDA,MD 20892, USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAY PY 1996 VL 20 IS 5 BP 644 EP 644 DI 10.1097/00000478-199605000-00015 PG 1 WC Pathology; Surgery SC Pathology; Surgery GA UG683 UT WOS:A1996UG68300015 ER PT J AU Sutherland, CM Chmiel, JS Bieligk, S Henson, DE Winchester, DP AF Sutherland, CM Chmiel, JS Bieligk, S Henson, DE Winchester, DP TI Patient characteristics, treatment, and outcome of unknown primary melanoma in the United States for the years 1981 and 1987 SO AMERICAN SURGEON LA English DT Article ID METASTATIC MALIGNANT-MELANOMA; PRIMARY SITE AB The American College of Surgeons performed a patient care and evaluation study of malignant melanoma for years 1981 and 1987 to determine the presenting symptoms, methods of evaluation, clinical management, and disease outcome. Previous reports on malignant melanoma of the skin, mucous membrane, and eye have been published. This report details the findings for 58 patients with malignant melanoma of an unknown primary diagnosed in 1981 and 87 patients diagnosed in 1987. The total number of patients was relatively small in comparison to all malignant melanoma patients. These patients were younger than the skin, ocular, and mucous membrane melanoma patients. There were significantly more males than females. When the anatomical site of a pathological positive node was known, it most frequently was in the axilla. Surgery, radiation therapy, and chemotherapy were frequently used in treatment of these patients. Although the overall prognosis is poor, some patients will have long term survival, and aggressive therapy should be considered for at least some of these patients. C1 TULANE UNIV,SCH MED,TULANE CANC CTR,NEW ORLEANS,LA 70112. NORTHWESTERN UNIV,SCH MED,DEPT PREVENT MED,CHICAGO,IL 60611. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. AMER COLL SURG,CHICAGO,IL. RP Sutherland, CM (reprint author), TULANE UNIV,SCH MED,DEPT SURG,1430 TULANE AVE,NEW ORLEANS,LA 70112, USA. NR 15 TC 10 Z9 10 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 1776 PEACHTREE RD, NW., SUITE 410N, ATLANTA, GA 30309-2352 SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD MAY PY 1996 VL 62 IS 5 BP 400 EP 406 PG 7 WC Surgery SC Surgery GA UG699 UT WOS:A1996UG69900017 PM 8615572 ER PT J AU Mootha, VK French, S Balaban, RS AF Mootha, VK French, S Balaban, RS TI Neutral carrier-based ''Ca2+-selective'' microelectrodes for the measurement of tetraphenylphosphonium SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID CA-2+-SELECTIVE MICROELECTRODES AB Ca2+-selective microelectrodes with Simon's neutral carrier ETH 1001 are commercially available and have been widely used for the measurement of both extra- and intracellular calcium. The electrodes demonstrate high selectivity against other cations such as magnesium, sodium, and potassium. We report, however, that the ETH 1001-based microelectrode is a superior tetraphenylphosphonium (TPP+)-sensitive electrode. The electrode exhibits a Nernstian response for [Ca2+] > 10(-5) RI but for [TPP+] > 10(-7) M. Using two different methods, we found that log k(TPPCa) (selectivity coefficient for TPP+ with respect to Ca2+) is in the range of -3.0 to -5.3. We argue that the ETH 1001 microelectrode can be used as a commercially available TPP+ electrode. We illustrate this application by making membrane potential recordings in respiring mitochondria. The results are identical to those obtained using conventional ion-exchange TPP+ electrodes. (C) 1996 Academic Press, Inc. RP Mootha, VK (reprint author), NHLBI,CARDIAC ENERGET LAB,BETHESDA,MD 20892, USA. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 12 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD MAY 1 PY 1996 VL 236 IS 2 BP 327 EP 330 DI 10.1006/abio.1996.0174 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA UJ495 UT WOS:A1996UJ49500019 PM 8660512 ER PT J AU Goldszal, AF Tretiak, OJ Liu, DD Hand, PJ AF Goldszal, AF Tretiak, OJ Liu, DD Hand, PJ TI Multimodality multidimensional image analysis of cortical and subcortical plasticity in the rat brain SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE multimodality imaging; image registration; brain mapping; brain plasticity; rat brain; imaging ID 3-DIMENSIONAL RECONSTRUCTION; SYSTEM AB In this work, we developed and implemented a multimodality multidimensional imaging system which is capable of generating and displaying anatomical and functional images of selected structures and processes within a vertebrate's central nervous system (CNS). The functional images an generated from [C-14]-2-deoxy-D-glucose (2DG) autoradiography whereas the anatomic images are derived from cytochrome oxidase (GO) histochemistry. This multi-modality imaging system has been used to study mechanisms underlying information processing in the rat brain. We have applied this technique to visualize and measure the plasticity (deformation) observed in the rat's whisker system due to neonatal lesioning of selected peripheral sensory organs. Application of this imaging system revealed detailed information about the shape, size, and directionality of selected cortical and subcortical structures. Previous 2-D imaging techniques were unable to deliver such holistic information. Another important issue addressed in this work is related to image registration problems. We developed an image registration technique which employs extrinsic fiduciary marks for alignment and is capable of registering images with subpixel accuracy. It uses the information from all available fiduciary marks to promote alignment of the sections and to avoid propagation of errors across a serial data set. C1 DREXEL UNIV, IMAGING & COMP VIS CTR, PHILADELPHIA, PA 19104 USA. UNIV PENN, MAHONEY INST NEUROL SCI, PHILADELPHIA, PA 19104 USA. UNIV PENN, SCH VET MED, DEPT ANIM BIOL, PHILADELPHIA, PA 19104 USA. RP NIA, GERONTOL RES CTR, LAB PERSONAL & COGNIT, 4940 EASTERN AVE, BOX 03, BALTIMORE, MD 21224 USA. FU NCRR NIH HHS [P41RR01638]; NINDS NIH HHS [NS22283] NR 28 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-6964 EI 1573-9686 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD MAY-JUN PY 1996 VL 24 IS 3 BP 430 EP 439 DI 10.1007/BF02660892 PG 10 WC Engineering, Biomedical SC Engineering GA UK318 UT WOS:A1996UK31800012 PM 8734064 ER PT J AU Yamase, HT Forouhar, FA Sojda, DF Cartun, RW Diwan, BA Kasprzak, BH Sunderman, FW AF Yamase, HT Forouhar, FA Sojda, DF Cartun, RW Diwan, BA Kasprzak, BH Sunderman, FW TI Immunoperoxidase staining of tumors by an antibody to Xenopus pNiXa SO ANNALS OF CLINICAL AND LABORATORY SCIENCE LA English DT Article ID N-NITROSODIETHYLAMINE; TISSUE BLOCK; PROTEIN; SERPIN; PROMOTION; LIVER; RATS; CARCINOGENESIS; INHIBITORS; INDUCTION AB pNiXa, a serpin from oocytes and embryos of Xenopus laevis, was tested as a tumor market in human and rodent tissues. A peptide corresponding to the histidine-rich domain of pNiXa was conjugated and administered to rabbits to produce a polyclonal antibody, which was purified by antigen-affinity and used for immunoperoxidase staining of formalin-fixed, paraffin-embedded tissue sections. Staining with pNiXa-antibody was positive in 23/187 human tumors (12 percent) and negative in 119 specimens of normal human tissues. Positive reactions were more frequent in liver (38 percent) and colon (34 percent) tumors than breast (18 percent), prostate (9 percent), mesothelioma (20 percent) or lung (0 percent) tumors. Staining was negative in human tumors fi-om other sites. Rodent tumors and preneoplastic foci induced by chemical carcinogens were surveyed for staining with pNiXa-antibody. Staining was positive in 10/10 hepatic lesions (hepatocellular foci, adenomas, carcinomas) induced in hybrid D2B6F1 mice by diethylnitrosamine and phenobarbital, whereas murine mammary tumors and thyroid, pituitary, renal, and colon tumors of F-344/CNr rats were negative. Thus, immunostaining with pNiXa-antibody identifies a subset of human and murine tumors; further studies are needed to determine if reactivity of pNiXa-antibody has diagnostic or prognostic significance. C1 UNIV CONNECTICUT,SCH MED,DEPT LAB MED,FARMINGTON,CT 06030. UNIV CONNECTICUT,SCH MED,DEPT PATHOL,FARMINGTON,CT 06030. UNIV CONNECTICUT,SCH MED,DEPT PHARMACOL,FARMINGTON,CT 06030. HAREFIELD HOSP,DEPT PATHOL & LAB MED,HARTFORD,CT 06102. NCI,BIOL CARCINOGENESIS & DEV PROGRAM,SAIC FREDERICK,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. FU NIEHS NIH HHS [ES-05331-05] NR 22 TC 2 Z9 2 U1 0 U2 1 PU INST CLINICAL SCIENCE INC PI PHILADELPHIA PA 1833 DELANCEY PLACE, PHILADELPHIA, PA 19103 SN 0091-7370 J9 ANN CLIN LAB SCI JI Ann. Clin. Lab. Sci. PD MAY-JUN PY 1996 VL 26 IS 3 BP 243 EP 251 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA UG104 UT WOS:A1996UG10400006 PM 8726217 ER PT J AU Burchfiel, CM Marcus, EB Sharp, DS Enright, PL Rodriguez, BL Masaki, KH Hwang, LJ Curb, JD AF Burchfiel, CM Marcus, EB Sharp, DS Enright, PL Rodriguez, BL Masaki, KH Hwang, LJ Curb, JD TI Characteristics associated with rapid decline in forced expiratory volume SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Asian-Americans; cigarette smoking; forced expiratory volume; pulmonary disease; cohort study; risk factors ID CORONARY HEART-DISEASE; OBSTRUCTIVE PULMONARY-DISEASE; JAPANESE-AMERICAN MEN; AIR-FLOW OBSTRUCTION; LUNG-FUNCTION; VENTILATORY FUNCTION; ALCOHOL-CONSUMPTION; CIGARETTE-SMOKING; REFERENCE VALUES; BODY-WEIGHT AB Cigarette smoking is known to accelerate decline of pulmonary Junction; however, the role of other factors is less clear, Characteristics of individuals who experienced rapid decline in forced expiratory volume in 1-sec (FEV(1)) were examined in 4451 Japanese-American men from the Honolulu Heart Program who were aged 45 to 68 years at baseline (1965-1968) and who produced three acceptable FEV(1) measures over a 6-year period. Average annual rates of FEV(1) decline were calculated by we of within-person regression and were categorized as rapid (greater than or equal to 60 ml/y), moderate (30 to 59 ml/y) or slow (< 30 ml/y). Lifestyle and biologic factors were compared by FEV(1) decline categories after adjustment for age. A logistic regression model showed that continued smoking during follow-up, cigarette pack-years, wheezing, coronary heart disease, alcohol intake, and reduced subscapular skinfold were significantly associated with rapid FEV(1) decline, after adjustment for age, height, cholesterol, an indicator of Japanese diet, and education. When analyses were restricted to continuous smokers, cigarette pack-years, wheezing, and reduced subscapular skinfold were found to be independent predictors. Among never smokers, lower educational attainment was a predictor of rapid FEV(1) decline, and the association involving subscapular skinfold approached significance (P < 0.07). These characteristics may be useful in identifying subgroups of the population who are at increased risk of accelerated decline in pulmonary function and thus would be most likely to benefit from appropriate intervention. C1 NHLBI,HONOLULU EPIDEMIOL RES UNIT,FIELD STUDIES & CLIN EPIDEMIOL SCI RES GRP,HONOLULU,HI. UNIV HAWAII,JOHN A BURNS SCH MED,DEPT MED,HONOLULU,HI 96822. UNIV ARIZONA,COLL MED,ARIZONA HLTH SCI CTR,DIV RESP SCI,TUCSON,AZ 85721. UNIV VIRGINIA,HLTH SCI CTR,NEUROCLIN TRIALS CTR,CHARLOTTESVILLE,VA 22903. RP Burchfiel, CM (reprint author), KUAKINI MED CTR,HONOLULU HEART PROGRAM,347 N KUAKINI ST,HONOLULU,HI 96817, USA. FU NHLBI NIH HHS [N01-HC-02901] NR 55 TC 35 Z9 36 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD MAY PY 1996 VL 6 IS 3 BP 217 EP 227 DI 10.1016/1047-2797(96)00007-5 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UM692 UT WOS:A1996UM69200008 PM 8827157 ER PT J AU Bild, DE Jacobs, DR Liu, K Williams, OD Hilner, JE Perkins, LL Marcovina, SM Hulley, SB AF Bild, DE Jacobs, DR Liu, K Williams, OD Hilner, JE Perkins, LL Marcovina, SM Hulley, SB TI Seven year trends in plasma low-density-lipoprotein-cholesterol in young adults: The CARDIA study SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE cholesterol; triglycerides; diet; body weight; aging; risk factors; trends; cohort study ID MINNESOTA HEART SURVEY; DISEASE RISK-FACTORS; CARDIOVASCULAR-DISEASE; UNITED-STATES; SERUM-LIPIDS; MORTALITY; NUTRITION AB To identify determinants of recent secular trends in lipids and characterize their influence on age-related increases in LDL-cholesterol, we examined a cohort of black and white men and women aged 18-30 in 1985-1986. Secular trends were determined by comparing participants aged 25-30 at baseline With those aged 25-30 at year 7 (2788 and 1395 participants, respectively). LDL-cholesterol was lower among those 25-30 at year 7 (5.9 to 10.2 mg/dL, depending on race-sex group; P < 0.001); weight was higher (8.3 to 12.5 lb; P < 0.001); Keys score was lower (-4.2 to -7.3 units; P < 0.001); and use of oral contraceptives was greater (white women only, P < 0.01). Among 4086 participants followed for 7 years, LDL-cholesterol changed little or decreased, despite substantial weight increases in all groups (11.6 to 19.0 lb; P < 0.001). Keys scores decreased by 6.1 to 8.0 units, and use of oral contraceptives decreased (P < 0.001). Declining secular trends in LDL-cholesterol occurred despite upward trends in weight; the decline was associated with lower dietary fat and cholesterol and offset expected age-related increases in LDL-cholesterol. C1 UNIV MINNESOTA,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455. NORTHWESTERN UNIV,CHICAGO,IL 60611. UNIV ALABAMA,CARDIA COORDINATING CTR,BIRMINGHAM,AL. DOW CORNING CORP,MIDLAND,MI. UNIV WASHINGTON,SEATTLE,WA 98195. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. RP Bild, DE (reprint author), NHLBI,DECA,2 ROCKLEDGE CTR,6701 ROCKLEDGE DR,MSC7934,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [N01-HC48047-48050, N01-HC95095] NR 38 TC 42 Z9 42 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD MAY PY 1996 VL 6 IS 3 BP 235 EP 245 DI 10.1016/1047-2797(96)00005-1 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UM692 UT WOS:A1996UM69200010 PM 8827159 ER PT J AU Allender, PS Cutler, JA Follmann, D Cappuccio, FP Pryer, J Elliott, P AF Allender, PS Cutler, JA Follmann, D Cappuccio, FP Pryer, J Elliott, P TI Dietary calcium and blood pressure: A meta-analysis of randomized clinical trials SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID ORAL CALCIUM; DOUBLE-BLIND; CONTROLLED INTERVENTION; ESSENTIAL-HYPERTENSION; NORMOTENSIVE SUBJECTS; MILD HYPERTENSION; SUPPLEMENTATION; CROSSOVER; MEN AB Purpose: To assess the effect of dietary calcium supplementation on blood pressure. Data Sources: Published reports of trials studying the effect of dietary calcium supplementation on blood pressure were identified by a search of previous reviews, a MEDLINE search, a manual review of journal articles, and a review of abstracts from scientific meetings. Study Selection: Randomized clinical trials in which dietary calcium intake varied by intervention group were selected. Multifactorial trials were not included. Data Synthesis: Data from 28 active treatment arms or strata from 22 randomized clinical trials were pooled using a weighted average method, with weights proportional to the inverse of the variance of the treatment effect. The total sample comprised 1231 persons. Because trials of both normotensive and hypertensive persons were included, subgroup analyses could be done. Pooled estimates of the effect of calcium supplementation on blood pressure were -0.18 mm Hg for diastolic blood pressure (95% CI, -0.75 to 0.40 mm Hg) and -0.89 mm Hg for systolic blood pressure (CI, -1.74 to -0.05 mm Hg). Pooled estimates for systolic blood pressure were -0.53 mm Hg (CI, -1.56 to 0.49 mm Hg) for trials of normotensive persons and -1.68 mm Hg (CI, -3.18 to -0.18 mm Hg) for trials of hypertensive persons. Diastolic blood pressure was not significantly affected in either subgroup. Conclusion: The pooled estimate shows a statistically significant decrease of systolic blood pressure with calcium supplementation, both for hypertensive persons and for the overall sample. However, the effect is too small to support the use of calcium supplementation for preventing or treating hypertension. C1 UNIV LONDON LONDON SCH HYG & TROP MED,DEPT PUBL HLTH & POLICY,LONDON WC1E 7HT,ENGLAND. RP Allender, PS (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,2 ROCKLEDGE CTR,ROOM 8132,6701 ROCKLEDGE DR,MSC 7,BETHESDA,MD 20892, USA. RI Cappuccio, Francesco/D-3028-2009; OI Cappuccio, Francesco Paolo/0000-0002-7842-5493 NR 39 TC 192 Z9 195 U1 1 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 1 PY 1996 VL 124 IS 9 BP 825 EP 831 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA UG254 UT WOS:A1996UG25400007 PM 8610952 ER PT J AU Papa, SM Chase, TN AF Papa, SM Chase, TN TI Levodopa-induced dyskinesias improved by a glutamate antagonist in Parkinsonian monkeys SO ANNALS OF NEUROLOGY LA English DT Article ID BASAL GANGLIA; L-DOPA; RATS AB Antagonists of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor have been reported to potentiate the antiparkinsonian action of levodopa and reverse levodopa-induced motor fluctuations in animal models of Parkinson's disease. To evalute the effect of NMDA receptor blockade on dyskinesias complicating the response to long-term levodopa therapy, we studied the selective antagonist LY235959 in six 1-methyl-4-phenyl-1,2,3,G-tetrahydropyridine-lesioned monkeys. Drugs were administered subcutaneously, LY235959 at doses of 0.5, 1.0, 3.0, and 5.0 mg/kg and levodopa/benserazide at doses that produced moderate dyskinesias while almost totally reversing parkinsonian signs. Compared with vehicle control injections, LY235959 (3.0 mg/kg) abolished oral dyskinesias and diminished choreic dyskinesias by 68% (p < 0.01). Lower doses had smaller effects, although still significant, on oral dyskinesias (55% reduction at 1.0 mg/kg, p < 0.05). The highest LY235959 dose (5.0 mg/kg) prolonged oral dyskinesia suppression, but tended to increase dystonia severity. LY235959 had no effect on motor function when given alone and did not reduce the antiparkinsonian response to levodopa. These findings suggest that NMDA receptor blockade may ameliorate the dyskinetic complications of long-term levodopa therapy, without diminishing the beneficial effects on parkinsonian signs. C1 NINCDS,EXPTL THERAPEUT BRANCH,NATL INST HLTH,BETHESDA,MD 20892. NR 20 TC 277 Z9 284 U1 0 U2 6 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 1996 VL 39 IS 5 BP 574 EP 578 DI 10.1002/ana.410390505 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UK339 UT WOS:A1996UK33900004 PM 8619541 ER PT J AU Major, EO AF Major, EO TI Oligodendroglial development in fetal cerebrum - Reply SO ANNALS OF NEUROLOGY LA English DT Letter RP Major, EO (reprint author), NINCDS,NIH,LAB MOL MED & NEUROSCI,BETHESDA,MD 20892, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 1996 VL 39 IS 5 BP 685 EP 685 DI 10.1002/ana.410390527 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UK339 UT WOS:A1996UK33900026 ER PT J AU Oeltgen, PR Horton, ND Bolling, SF Su, TP AF Oeltgen, PR Horton, ND Bolling, SF Su, TP TI Extended lung preservation with the use of hibernation trigger factors SO ANNALS OF THORACIC SURGERY LA English DT Article ID AUTOPERFUSION MULTIORGAN PREPARATION; MAJOR ORGANS; TRANSPLANTATION; HEART; MONKEY AB Background. The complications of preserving lungs for transplantation are well known, with successful transplantation only being assured by preservation times of 5 to 6 hours or less. If a new method of consistent lung preservation could be identified, lung transplantation could be extended to many patients. We have previously reported lung preservation times averaging 14.8 hours using a multiorgan autoperfusion block infused with physiologic saline solution as a model. When plasma from deeply hibernating woodchucks (Marmota monax) or the delta opioid DADLE was infused into the multiorgan block, lung preservation times increased threefold to 45 hours. Methods. In this study, we examined the effect of infusing plasma containing the hibernation induction trigger molecule on lung preservation for transplantation using a multiorgan autoperfusion block. Results. This study demonstrated that successful orthotopic transplantation of single canine lungs is possible after 24 to 33 hours of preservation when the lung has been maintained with plasma containing the hibernation induction trigger molecule. Conclusions. Theoretically, hibernation induction trigger could be administered to donors before lung harvest in an effort to extend lung preservation times. C1 VET ADM MED CTR,DEPT PATHOL & LAB MED,PATHOL SERV,LEXINGTON,KY. UNIV KENTUCKY,GRAD CTR TOXICOL,LEXINGTON,KY. UNIV MICHIGAN,DEPT SURG,ANN ARBOR,MI 48109. NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. NR 24 TC 45 Z9 46 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAY PY 1996 VL 61 IS 5 BP 1488 EP 1493 DI 10.1016/0003-4975(96)00108-7 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA UG909 UT WOS:A1996UG90900049 PM 8633964 ER PT J AU Korytynski, EA Kelloff, GJ Suk, WA Sharma, S Elmore, E AF Korytynski, EA Kelloff, GJ Suk, WA Sharma, S Elmore, E TI The development of an anchorage-independence assay using human lung tumor cells to screen potential chemopreventive agents SO ANTICANCER RESEARCH LA English DT Article DE in vitro model; anchorage-independent growth; chemoprevention; 13-cis-retinoic acid ID PREVENTION AB Advances in tumor biology research have led to the possibility of early detection of cancers and rational intervention of cancer development using chemopreventive agents. A significant number of potential chemopreventive agents have been identified from epidemiological surveys, independent research efforts, clinical data or based on structural homology with known chemopreventive agents. We have developed a fast, reliable in vitro model for screening potential chemopreventive agents using inhibition of anchorageindependent growth of a human lung tumor cell line, A427. A427 cells were plated in soft agarose containing a known chemopreventive agent, 13-cis-retinoic acid as the test agent and allowed to develop colonies for 28 days. A cytotoxicity test was used concurrently with anchorage independent assay for measuring the relative survival of cells to ensure that any observed inhibition of anchorage independent growth is due to the biological activity of the chemopreventive agent and not due to cellular toxicity. At the end of 28 days of growth, the stained colonies were enumerated, and the inhibition of spontaneous colony formation was measured. 13-cis-Retinoic acid inhibited the growth of A427 colonies in a concentration dependent manner. Data from 25 successive experiments indicate that a concentration of 33 mu M consistently inhibited colony formation by 66.2 +/- 16.5 percent, ranging from 27 to 96.1 % inhibition. This assay is a useful tool for screening potential chemopreventive agents, as it uses human cells as substrates rendering the efficacy data feasible for direct extrapolation to humans. C1 MANTECH ENVIRONM TECHNOL INC,CELLULAR & MOL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. NCI,DIV CANC PREVENT & CONTROL,CHEMOPREVENT BRANCH,NIH,BETHESDA,MD 20892. NIEHS,RES TRIANGLE PK,NC 27709. UNIV CALIF IRVINE,IRVINE,CA 92717. FU NCI NIH HHS [N01-CN-55503-04, N01-CN55503-02, N01-CN-95172-01] NR 13 TC 7 Z9 8 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAY-JUN PY 1996 VL 16 IS 3A BP 1091 EP 1094 PG 4 WC Oncology SC Oncology GA UR869 UT WOS:A1996UR86900003 PM 8702218 ER PT J AU DeLucca, AJ Walsh, TJ Daigle, DJ AF DeLucca, AJ Walsh, TJ Daigle, DJ TI N-acetylcysteine inhibits germination of conidia and growth of Aspergillus spp and Fusarium spp SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID DIAGNOSIS; FUMIGATUS; CYSTEINE AB N-Acetylcysteine inhibited hyphal growth and germination of conidia of Aspergillus spp. and Fusarium spp. N-Acetylcysteine inhibited conidial germination as well as or better than L-cysteine. Cysteine-related compounds may provide a potential therapeutic strategy against agriculturally and medically important fungal pathogens. C1 NCI,INFECT DIS SECT,PEDIAT BRANCH,BETHESDA,MD 20892. ARS,SO REG RES CTR,USDA,NEW ORLEANS,LA. NR 29 TC 15 Z9 15 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 1996 VL 40 IS 5 BP 1274 EP 1276 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA UJ076 UT WOS:A1996UJ07600041 PM 8723482 ER PT J AU Washburn, BS Vines, CA Baden, DG Hinton, DE Walsh, PJ AF Washburn, BS Vines, CA Baden, DG Hinton, DE Walsh, PJ TI Differential effects of brevetoxin and beta-naphthoflavone on xenobiotic metabolizing enzymes in striped bass (Morone saxatilis) SO AQUATIC TOXICOLOGY LA English DT Article DE brevetoxin; BNF; xenobiotic metabolizing enzymes; biomarker; glutathione S-transferase; cytochrome P450IA ID GLUTATHIONE-S-TRANSFERASE; RAINBOW-TROUT; CYTOCHROME-P-450-DEPENDENT MONOOXYGENASE; EPOXIDE HYDROLASE; SALMO-GAIRDNERI; INDUCTION; LIVER; FISH; SYSTEMS; KIDNEY AB The goal of this study was to determine the effects of brevetoxin, a polyether marine biotoxin, on xenobiotic metabolizing enzymes and to identify potential biomarkers of exposure. Brevetoxin (PbTx) is responsible for the death of millions of fish during algals blooms or 'red tides', To this end, striped bass (Morone saxatilis) were exposed to either brevetoxin; a positive control, beta-naphthoflavone (BNF); or a negative control, the toxicant solvent, for five days. Hepatic microsomal and cytosolic fractions were prepared and assayed for ethoxyresorufin O-deethylase (EROD), UDP glucuronosyl transferase, microsomal epoxide hydrolase, and four isozymes of glutathione S-transferase, BNF induced a 30 fold increase in EROD activity; PbTx caused a 3 fold increase in EROD activity as well as 35 and 50 percent increase in the activity of two GST isozymes. Although PbTx is not an aromatic molecule, the present findings validates previous work with another species fish, redfish (Scaienops ocellatus), that PbTx induces Cytochrome P450IA activity. As is characteristic for molecules with Michael acceptor groups, PbTx also induced the GST, in particular those isozymes sensitive to ethacrynic acid and trnns-phenylbutenone (pi and mu forms in mammals). Brevetoxin's affect on GST isozymes make them potentially useful biomarkers. C1 UNIV CALIF BODEGA, MARINE LAB, BODEGA BAY, CA 94923 USA. UNIV MIAMI, ROSENSTIEL SCH MARINE & ATMOSPHER SCI, NIEHS, MARINE & FRESHWATER BIOMED SCI CTR, MIAMI, FL 33149 USA. RP Washburn, BS (reprint author), UNIV CALIF DAVIS, SCH VET MED, DEPT ANAT PHYSIOL & CELL BIOL, DAVIS, CA 95616 USA. NR 25 TC 23 Z9 25 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-445X J9 AQUAT TOXICOL JI Aquat. Toxicol. PD MAY PY 1996 VL 35 IS 1 BP 1 EP 10 DI 10.1016/0166-445X(95)00050-E PG 10 WC Marine & Freshwater Biology; Toxicology SC Marine & Freshwater Biology; Toxicology GA UY460 UT WOS:A1996UY46000001 ER PT J AU Schlegel, M Lom, J Stechmann, A Bernhard, D Leipe, D Dykova, I Sogin, ML AF Schlegel, M Lom, J Stechmann, A Bernhard, D Leipe, D Dykova, I Sogin, ML TI Phylogenetic analysis of complete small subunit ribosomal RNA coding region of Myxidium lieberkuehni: Evidence that Myxozoa are Metazoa and related to the Bilateria SO ARCHIV FUR PROTISTENKUNDE LA English DT Article DE Myxozoa phylogeny; Nematocyst evolution; Myxidium lieberkuehni; small subunit rRNA ID SEQUENCES; ULTRASTRUCTURE; SPOROGENESIS; MYXOSPOREA; DISTINCT; GENES AB The phylogenetic position of Myxozoa relative to other eukaryotes has been controversial. During their complex life cycles they show both protist and metazoan characters. In contrast to their general classification as protists, phylogenetic comparisons of the complete 16S-like rRNA sequence of the myxosporean Myxidium lieberkuehni with other, unicellular and metazoan sequences show that Myxozoa share a common evolutionary history with Metazoa and are most closely related to the Bilateria. C1 ACAD SCI CZECH REPUBL,INST PARASITOL,CR-37005 CESKE BUDEJOVICE,CZECH REPUBLIC. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. BIOL MARINE LAB,WOODS HOLE,MA. RP Schlegel, M (reprint author), UNIV LEIPZIG,INST ZOOL,TALSTR 33,D-04103 LEIPZIG,GERMANY. RI Dykova, Iva/B-9699-2013 NR 30 TC 90 Z9 95 U1 0 U2 7 PU GUSTAV FISCHER VERLAG JENA PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0003-9365 J9 ARCH PROTISTENKD JI Arch. Protistenkd. PD MAY PY 1996 VL 147 IS 1 BP 1 EP 9 PG 9 WC Microbiology SC Microbiology GA UU094 UT WOS:A1996UU09400001 ER PT J AU Silverman, K Higgins, ST Brooner, RK Montoya, ID Cone, EJ Schuster, CR Preston, KL AF Silverman, K Higgins, ST Brooner, RK Montoya, ID Cone, EJ Schuster, CR Preston, KL TI Sustained cocaine abstinence, in methadone maintenance patients through voucher-based reinforcement therapy SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 56th Annual Scientific Meeting of the College-on-Problems-in-Drug-Dependence CY JUN 18-23, 1994 CL PALM BEACH, FL SP Coll Problems Drug Dependence ID BEHAVIORAL-APPROACH; VALIDITY AB Background: Chronic cocaine abuse remains a serious and costly public health problem. This study assessed the effectiveness of a voucher-based reinforcement contingency in producing sustained cocaine abstinence. Methods: A randomized controlled trial compared voucher-based reinforcement of cocaine abstinence to noncontingent voucher presentation. Patients were selected from 52 consecutively admitted injecting heroin abusers in a methadone maintenance treatment program. Patients with heavy cocaine use during baseline period (N=37) participated. Except where otherwise indicated, the term cocaine abuse is used in this article in a generic sense and not according to the DSM-III-R definition. Patients exposed to abstinence reinforcement received a voucher for each cocaine-free urine sample (ie, negative for benzoylecgonine) provided three times per week throughout a 12-week period; the vouchers had monetary values that increased as the number of consecutive cocaine-free urine samples increased. Control patients received noncontingent vouchers that were matched in pattern and amount to the vouchers received by patients in the abstinence reinforcement group. Results: Patients receiving vouchers for cocaine-free urine samples achieved significantly more weeks of cocaine abstinence (P=.007) and significantly longer durations of sustained cocaine abstinence (P=.001) than controls. Nine patients (47%) receiving vouchers for cocaine-free urine samples achieved between 7 and 12 weeks of sustained cocaine abstinence; only one control patient (6%) achieved more than 2 weeks of sustained abstinence. Among patients receiving vouchers for cocaine-free urine samples, those who achieved sustained abstinence (greater than or equal to 5 weeks) had significantly lower concentrations of benzoylecgonine in baseline urine samples than those who did not achieve sustained abstinence (P less than or equal to.01). Patients receiving voucher reinforcement rated the overall treatment quality significantly higher than controls (P=.002). Conclusion: Voucher-based reinforcement contingencies can produce sustained cocaine abstinence in injecting polydrug abusers. C1 NIDA,ADDICT RES CTR,INTRAMURAL RES PROGRAM,DIV INTRAMURAL RES,CLIN TRIALS SECT,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21218. UNIV VERMONT,COLL MED,BURLINGTON,VT 05405. RI Preston, Kenzie/J-5830-2013; OI Preston, Kenzie/0000-0003-0603-2479; Silverman, Kenneth/0000-0003-2724-1413 NR 34 TC 288 Z9 288 U1 0 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAY PY 1996 VL 53 IS 5 BP 409 EP 415 PG 7 WC Psychiatry SC Psychiatry GA UJ819 UT WOS:A1996UJ81900004 PM 8624184 ER PT J AU Yannuzzi, LA Sorenson, JA Sobel, RS Daly, JR DeRosa, JT Seddon, JM Gragoudas, ES Puliafito, CA Gelles, E Gonet, R Burton, TC Culver, J Metzger, K Kalbfleisch, N Zarling, D Farber, MD Blair, N Stelmack, T Axelrod, A Waitr, SE Cross, A Rolnick, C Flom, T Haller, J Pusin, S Cassel, G Appelgate, CA Sperduto, RD Seigel, D Hiller, R Mowery, R Chew, E Tamboli, A Dunn, M Shamban, K Lento, D AF Yannuzzi, LA Sorenson, JA Sobel, RS Daly, JR DeRosa, JT Seddon, JM Gragoudas, ES Puliafito, CA Gelles, E Gonet, R Burton, TC Culver, J Metzger, K Kalbfleisch, N Zarling, D Farber, MD Blair, N Stelmack, T Axelrod, A Waitr, SE Cross, A Rolnick, C Flom, T Haller, J Pusin, S Cassel, G Appelgate, CA Sperduto, RD Seigel, D Hiller, R Mowery, R Chew, E Tamboli, A Dunn, M Shamban, K Lento, D TI Risk factors for central retinal vein occlusion - The eye disease case-control study group SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID ALCOHOL-CONSUMPTION; HEART-DISEASE; CLASSIFICATION AB Objective: To identify possible risk factors for central retinal vein occlusion (CRVO). Design: Between May 1, 1986, and December 31, 1990, 258 patients with CRVO and 1142 controls were identified at five clinical centers. Data were obtained through interviews, clinical examinations, and laboratory analyses of blood specimens. Results: An increased risk of CRVO was found in persons with systemic hypertension, diabetes mellitus, and open-angle glaucoma. Risk of CRVO decreased with increasing levels of physical activity and increasing levels of alcohol consumption. In women, risk of occlusion decreased with use of postmenopausal estrogens and increased with higher erythrocyte sedimentation rates. Cardiovascular disease, electrocardiographic abnormalities, history of treatment of diabetes mellitus, higher blood glucose levels, lower albumin-globulin ratios, and higher alpha(1)-globulin levels were associated with increased risk only for ischemic CRVO. Systemic hypertension was associated with increased risk for ischemic and nonischemic CRVO, but odds ratios were greater for the ischemic type. Conclusions: Our results suggest a cardiovascular risk profile for persons with CRVO, in particular, patients with the ischemic type. The findings reinforce recommendations to diagnose and treat systemic hypertension, advise patients to increase physical exercise, and consider use of exogenous estrogens in postmenopausal women. C1 NEI,DIV BIOMETRY & EPIDEMIOL,BETHESDA,MD 20892. MANHATTAN EYE EAR & THROAT HOSP,NEW YORK,NY 10021. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. MED COLL WISCONSIN,MILWAUKEE,WI 53226. UNIV ILLINOIS,CHICAGO,IL. JOHNS HOPKINS UNIV HOSP,WILMER EYE INST,BALTIMORE,MD. ORKAND CORP,COORDINATING CTR,SILVER SPRING,MD. PHOTOG READING CTR,BOSTON,MA. NR 31 TC 189 Z9 191 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAY PY 1996 VL 114 IS 5 BP 545 EP 554 PG 10 WC Ophthalmology SC Ophthalmology GA UJ223 UT WOS:A1996UJ22300005 ER PT J AU Woods, GL Long, TA Witebsky, FG AF Woods, GL Long, TA Witebsky, FG TI Mycobacterial testing in clinical laboratories that participate in the College of American Pathologists mycobacteriology surveys - Changes in practices based on responses to 1992, 1993, and 1995 questionnaires SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID TUBERCULOSIS AB Objective.-To determine whether the trend of increasing use of rapid methods of mycobacterial testing among participants in the College of American Pathologists (CAP) Mycobacteriology E Proficiency Testing Survey noted between 1992 and 1993 continued through 1995, and to collect information concerning mycobacterial staining and culture protocols from laboratories that do limited mycobacterial testing. Methods.-The 1993 CAP E Survey questionnaire addressing mycobacterial laboratory practices, test volumes, and rate of recovery of drug-resistant Mycobacterium tuberculosis was included with the CAP 1995 E-A Survey. A shortened list of these same questions, excluding those addressing mycobacterial identification and susceptibility test methods, was added to the CAP 1995 E1-A Survey, to which laboratories that do limited mycobacterial testing subscribe. Results.-A total of 802 and 1490 participants in the E and El surveys, respectively, returned responses to the CAP by the cutoff date for data analysis. For E Survey participants who answered questions concerning test methods in the years being compared, the percentage who used rapid techniques increased significantly over the study period. More participants used the fluorochrome stain (58% in 1992, 62% in 1993, and 72% in 1995), BACTEC TB plus a solid medium for culture (36% in 1992, 42% in 1993, and 50% in 1995), DNA probes for identification of M tuberculosis (68% in 1993, 79% in 1995), and BACTEC TB for susceptibility testing (65% in 1993, 71% in 1995). The percentages of El Survey participants who used a fluorochrome stain for detection of acid-fast bacilli and both a liquid and a solid medium for mycobacterial culture were lower than the percentages of E Survey participants who used these methods. Among participants who responded in all years being compared, the percentage processing respiratory specimens at least 7 times per week increased from 26% in 1992 to 30% in 1993 and 43% in 1995 (P <.001), and the percentages reporting an identification of M tuberculosis within 21 days and susceptibility test results within 28 days increased significantly over the study period (29% in 1992, 40% in 1993, and 56% in 1995 for identification; 13% in 1992, 19% in 1993, and 30% in 1995 for susceptibility testing). Turnaround times for E Survey participants were significantly shorter than those for El Survey participants. The number of specimens tested per month appeared to remain relatively stable between 1993 and 1995; however, the number of new patients with tuberculosis and the number of known tuberculosis patients with positive cultures declined significantly. Conclusions.-The recent emphasis placed on utilization of rapid methods of mycobacterial testing appears to have influenced laboratories that subscribe to the CAP E Survey. Significantly more of these laboratories were following the Centers for Disease Control and Prevention's recommendations in 1995 than in 1993 and 1992. However, many laboratories that provide only limited mycobacterial testing still have not adopted the more rapid techniques. Because tuberculosis remains a public health problem, the efforts directed at its control must not wane if the recent downward trend in incidence is to be maintained. C1 COLL AMER PATHOLOGISTS,DEPT BIOSTAT,NORTHFIELD,IL. NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,MICROBIOL SERV,BETHESDA,MD 20892. RP Woods, GL (reprint author), UNIV TEXAS,MED BRANCH,DEPT PATHOL,GALVESTON,TX 77555, USA. FU NHLBI NIH HHS [1 K07 HL0333-01] NR 14 TC 15 Z9 15 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAY PY 1996 VL 120 IS 5 BP 429 EP 435 PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA UN128 UT WOS:A1996UN12800008 PM 8639044 ER PT J AU Woods, GL Witebsky, FG AF Woods, GL Witebsky, FG TI Susceptibility testing of Mycobacterium avium complex in clinical laboratories - Results of a questionnaire and proficiency test performance by participants in the College of American Pathologists Mycobacteriology E Survey SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID INFECTION; AIDS AB Objectives.-To obtain information regarding the frequency and methodology of susceptibility testing of Mycobacterium avium complex (MAC) in clinical microbiology laboratories, and to assess interlaboratory reproducibility of MAC susceptibility testing. Design.-Questions addressing MAC susceptibility testing were added to the College of American Pathologists' 1994 Mycobacteriology E Proficiency Testing Survey, and participants were asked to complete the questionnaire. In addition, participants in the 1994 E Survey were asked to test susceptibility of a MAC isolate recovered from a proficiency testing specimen as an ungraded exercise if they offered such testing for patients. Results.-Of the 1003 participants enrolled in the 1994 Mycobacteriology E-A Survey, 806 responded to one or more supplemental questions. In regard to the demand for MAC susceptibility testing, 606 participants indicated that the test is requested by physicians in their institutions, and 188 said that they do the test routinely on al least one MAC isolate per patient. Eighty-two percent (630/765) of participants refer the test to an outside laboratory, most commonly a commercial reference laboratory or state health laboratory. Of the 70 participants who perform MAC susceptibility testing in-house and indicated the method on the questionnaire, 54 (77%) used a solid medium, whereas only 44 (20%) used BACTEC TB, which currently is the recommended method. The most frequently tested drugs were ethambutol, rifampin, isoniazid, and streptomycin; other commonly evaluated agents were ciprofloxacin, amikacin, and clarithromycin. Only eight participants modify the pH of the medium when testing a macrolide. In regard to reporting test results, 56% (45/80) report a qualitative result only, 35% (28/80)report a quantitative result with ?I qualitative interpretation, and 9% (7/ 80) report only a quantitative result. Participant performance on the MAC proficiency testing specimen showed lack of interlaboratory reproducibility; 80% or fewer participants reported the correct result for all drugs except amikacin, for which 92% (11/17) of laboratories responded correctly. Conclusions.-Given the obvious interest in MAC susceptibility testing, standardized methodology that demonstrates interlaboratory reproducibility and, optimally, shows some correlation with clinical outcome is needed. Moreover, recommendations concerning indications for performing the test would be useful. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,MICROBIOL SERV,BETHESDA,MD 20892. RP Woods, GL (reprint author), UNIV TEXAS,MED BRANCH,DEPT PATHOL,GALVESTON,TX 77555, USA. NR 14 TC 4 Z9 4 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAY PY 1996 VL 120 IS 5 BP 436 EP 439 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA UN128 UT WOS:A1996UN12800009 PM 8639045 ER PT J AU Shankaran, S Bauer, CR Bain, R Wright, LL Zachary, J AF Shankaran, S Bauer, CR Bain, R Wright, LL Zachary, J TI Prenatal and perinatal risk and protective factors for neonatal intracranial hemorrhage SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID GERMINAL MATRIX HEMORRHAGE; BIRTH-WEIGHT INFANTS; PERIVENTRICULAR-INTRAVENTRICULAR HEMORRHAGE; RESPIRATORY-DISTRESS SYNDROME; BLOOD-BRAIN-BARRIER; 28 WEEKS GESTATION; PRETERM INFANTS; PREMATURE-INFANTS; CONTROLLED TRIAL; DELIVERY AB Objective: To identify prenatal and perinatal risk and protective factors for grade III and IV intracranial hemorrhage (ICH) in 4795 singleton infants (weight, less than or equal to 1500 g). Method: Prenatal and perinatal risk and protective factors for ICH were examined initially by univariate analysis and adjusted for year of birth, followed by multivariate logistic regression analysis that adjusted simultaneously for the effects of year of birth and prenatal and perinatal characteristics. Setting: Seven tertiary care neonatal-perinatal centers. Results: By univariate analysis, African-American race, prenatal care, older maternal age, hypertension or preeclampsia, antenatal steroid administration, cesarean section delivery, increasing birth weight, increasing gestational age, and female gender of the infant were protective prenatal or perinatal factors. Antepartum hemorrhage, the presence of labor, and breech presentation were perinatal factors that were associated with an increased risk of ICH. By using staged logistic regression, a model of combined prenatal and perinatal characteristics that influenced grade III and IV ICH was developed. Significant protective factors against ICH included a complete course of antenatal steroid therapy, African-American maternal race, female gender of the infant, hypertension or preeclampsia with no antepartum hemorrhage, increasing gestational age, and increasing birth weight. Conclusion: Antenatal steroid administration is a therapeutic intervention that is associated with a decreased risk for neonatal grade III and IV ICH. C1 WAYNE STATE UNIV,DETROIT,MI. UNIV MIAMI,CORAL GABLES,FL 33124. GEORGE WASHINGTON UNIV,CTR BIOSTAT,ROCKVILLE,MD. NICHHD,BETHESDA,MD 20892. RP Shankaran, S (reprint author), CHILDRENS HOSP MICHIGAN,DEPT NEONATOL,3901 BEAUBIEN,DETROIT,MI 48201, USA. FU NICHD NIH HHS [U10 HD21385, U01 HD19897, U10 HD21397] NR 39 TC 64 Z9 66 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD MAY PY 1996 VL 150 IS 5 BP 491 EP 497 PG 7 WC Pediatrics SC Pediatrics GA UJ619 UT WOS:A1996UJ61900009 PM 8620230 ER PT J AU Boyce, WT Higley, JD Jemerin, JJ Champoux, M Suomi, SJ AF Boyce, WT Higley, JD Jemerin, JJ Champoux, M Suomi, SJ TI Tympanic temperature asymmetry and stress behavior in rhesus macaques and children SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID MEMBRANE TEMPERATURES; THERMOMETER; EMOTION; MONKEYS AB Objectives: To examine left-to-right tympanic membrane temperature asymmetries and their possible association with biobehavioral stress responses in rhesus macaques and children. Subjects and Design: Infrared tympanic membrane thermometry was completed bilaterally in 19 two-year-old rhesus macaques and 18 eight-year-old children in a cross-sectional, laboratory-based study. Unidirectional temperature gradients were calculated as the mean of two left-sided measurements minus the mean of two right-sided measurements. Biobehavioral stress responses were assessed in monkeys as agitated motor activity and adrenocortical activation after separation from the social group, and in children as parent-reported resilience to psychological stress and child behavior problems. Results: Significant asymmetry was detected in tympanic membrane temperatures in both monkey and child samples, with left-sided temperatures measuring slightly but significantly higher than those from the right tympanic membrane. Higher-magnitude left-to-right temperature gradients were associated with stress-related locomotion in macaques and with lower resilience and more behavior problems in children. Conclusions: There are small but reliable asymmetries in the tympanic membrane temperatures of young human and nonhuman primates. Tympanic membrane temperature gradients reflect important individual differences in biologically derived responses to psychological stressors. C1 UNIV CALIF BERKELEY,SCH PUBL HLTH,BERKELEY,CA. UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,DIV BEHAV & DEV PEDIAT,SAN FRANCISCO,CA 94143. NICHHD,COMPARAT ETHOL LAB,BETHESDA,MD 20892. RP Boyce, WT (reprint author), UNIV CALIF BERKELEY,INST HUMAN DEV,BERKELEY,CA 94720, USA. FU NICHD NIH HHS [1RO1 HD 24718] NR 41 TC 24 Z9 24 U1 2 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD MAY PY 1996 VL 150 IS 5 BP 518 EP 523 PG 6 WC Pediatrics SC Pediatrics GA UJ619 UT WOS:A1996UJ61900014 PM 8620235 ER PT J AU Torpy, DJ Chrousos, GP AF Torpy, DJ Chrousos, GP TI The three-way interactions between the hypothalamic-pituitary-adrenal and gonadal axes and the immune system SO BAILLIERES CLINICAL RHEUMATOLOGY LA English DT Review ID CORTICOTROPIN-RELEASING HORMONE; INSULIN-INDUCED HYPOGLYCEMIA; ARGININE VASOPRESSIN; ADRENOCORTICOTROPIN RELEASE; RHEUMATOID-ARTHRITIS; LEWIS RATS; BIOCHEMICAL MANIFESTATIONS; SEX-DIFFERENCES; NERVOUS-SYSTEM; NORMAL MEN C1 NICHHD,PEDIAT ENDOCRINOL SECT,NIH,BETHESDA,MD 20892. GEORGETOWN UNIV,WASHINGTON,DC. RP Torpy, DJ (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,9000 ROCKVILLE PIKE,BLDG 10,ROOM 10N262,BETHESDA,MD 20892, USA. NR 109 TC 45 Z9 46 U1 0 U2 3 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0950-3579 J9 BAILLIERE CLIN RHEUM JI Baillieres Clin. Rheumatol. PD MAY PY 1996 VL 10 IS 2 BP 181 EP 198 PG 18 WC Rheumatology SC Rheumatology GA UP439 UT WOS:A1996UP43900002 PM 8911646 ER PT J AU Wilder, RL AF Wilder, RL TI Hormones and autoimmunity: Animal models of arthritis SO BAILLIERES CLINICAL RHEUMATOLOGY LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; COLLAGEN-INDUCED ARTHRITIS; PITUITARY-ADRENAL AXIS; ESTROGEN-INDUCED SUPPRESSION; WALL INDUCED POLYARTHRITIS; X-LINKED IMMUNODEFICIENCY; SUSCEPTIBLE LEWIS RATS; MRL LPR/LPR MICE; INFLAMMATORY DISEASE; RHEUMATOID-ARTHRITIS RP Wilder, RL (reprint author), NIAMSD,INFLAMMATORY JOINT DIS SECT,NIH,BLDG 10,ROOM 9N228,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 68 TC 39 Z9 39 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0950-3579 J9 BAILLIERE CLIN RHEUM JI Baillieres Clin. Rheumatol. PD MAY PY 1996 VL 10 IS 2 BP 259 EP 271 DI 10.1016/S0950-3579(96)80017-3 PG 13 WC Rheumatology SC Rheumatology GA UP439 UT WOS:A1996UP43900005 PM 8911649 ER PT J AU Miyamoto, S Chiorini, JA Urcelay, E Safer, B AF Miyamoto, S Chiorini, JA Urcelay, E Safer, B TI Regulation of gene expression for translation initiation factor elF-2 alpha: Importance of the 3' untranslated region SO BIOCHEMICAL JOURNAL LA English DT Article ID PROTEIN-SYNTHESIS-INITIATION; AU-RICH SEQUENCES; 2 MESSENGER-RNAS; TRANSCRIPTION TERMINATION; POLY(A); POLYADENYLATION; IDENTIFICATION; SITE; LYMPHOCYTES; DEGRADATION AB Gene expression of the alpha-subunit of eukaryotic initiation factor-2 (eIF-2 alpha), involves transcriptional and post-transcriptional mechanisms, eIF-2 alpha is a single-copy gene expressing two mRNAs, 1.6 and 4.2 kb in size, Cloning and sequencing of the cDNA for the 4.2 kb mRNA revealed that it is the result of alternative polyadenylation site selection. Four polyadenylation sites were identified within the 3' untranslated region (UTR) of eIF-2 alpha, only two of which are normally utilized in human and mouse tissues. A functional role for the extended 3' UTR was assessed by comparing the translatability and stability of the 1.6 and 4.2 kb mRNAs. Both the 1.6 and 4.2 kb transcripts could be translated in vitro and were identified in vivo as being distributed on large polyribosomes, This indicates that both mRNAs are efficiently translated. Stability studies showed that in activated T-cells the 4.2 kb mRNA was more stable than the 1.6 kb mRNA. Polyadenylation site selection and mRNA stability differ for the two mRNAs of eIF-2 alpha. These activities might be modulated by sequence elements contained within the untranslated regions of the eIF-2 alpha gene. RP Miyamoto, S (reprint author), NHLBI,MOLEC HEMATOL BRANCH,SECT PROT & RNA BIOSYNTH,BLDG 10,ROOM 7D18,10 CTR DR MSC 1654,BETHESDA,MD 20892, USA. NR 41 TC 50 Z9 50 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAY 1 PY 1996 VL 315 BP 791 EP 798 PN 3 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UK894 UT WOS:A1996UK89400014 PM 8645159 ER PT J AU Earley, K Luo, WP Qiu, YH Thompson, NL Chou, J Hixson, DC Lin, SH AF Earley, K Luo, WP Qiu, YH Thompson, NL Chou, J Hixson, DC Lin, SH TI Identification of a new isoform of cell-cell adhesion molecule 105 (C-CAM), C-CAM4: A secretory protein with only one Ig domain SO BIOCHEMICAL JOURNAL LA English DT Article ID HUMAN CARCINOEMBRYONIC ANTIGEN; RAT-LIVER; INTERCELLULAR-ADHESION; BILIARY GLYCOPROTEIN; ECTO-ATPASE; CDNA CLONES; EXPRESSION; MEMBRANE; TISSUES; FAMILY AB A series of Southern blot hybridization experiments using probes derived from different regions of the rat liver cell-cell adhesion molecule 105 (C-CAM) cDNA revealed the presence of a 9.6 kb EcoRI genomic fragment that seemed to encode a unique C-CAM isoform. An RNase protection study showed that this C-CAM transcript was expressed in placenta, spleen, lung and large intestine. In contrast, the other C-CAM isoforms, C-CAM1 and C-CAM2, are expressed in liver and small intestine. This result also suggests that the new isoform, which we named C-CAM4, was indeed encoded by a new C-CAM gene. A rat placenta cDNA library was then screened and the full-length cDNA coding for C-CAM4 was isolated. The deduced protein contained 142 amino acids and had a calculated molecular mass of 15 kDa. C-CAM4 was composed of a leader sequence and the first V-like Ig domain typical of C-CAM-family proteins. However, C-CAM4 lacked the C-like Ig domains, the transmembrane domain, and the cytoplasmic domain found in other C-CAM isoforms. Thus, C-CAM4 is different from the other known C-CAMs in that it is a secreted protein. We have previously shown that the first Ig domain of C-CAM1 is crucial for its adhesion function, The V-like Ig domain of C-CAM4 had 92% and 89% sequence identity with the corresponding regions of C-CAM1 and C-CAM2 respectively. Together these results suggest that C-CAM4 may play a role in regulating the function of other C-CAM family proteins. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT MOLEC PATHOL,HOUSTON,TX 77030. BROWN UNIV,RHODE ISL HOSP,DEPT MED ONCOL,PROVIDENCE,RI 02903. NIH,SECT CELL DIFFERENTIAT,BETHESDA,MD 20892. FU NCI NIH HHS [CA42715]; NIGMS NIH HHS [GM43189] NR 37 TC 7 Z9 7 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAY 1 PY 1996 VL 315 BP 799 EP 806 PN 3 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UK894 UT WOS:A1996UK89400015 PM 8645160 ER PT J AU Maher, F DaviesHill, TM Simpson, IA AF Maher, F DaviesHill, TM Simpson, IA TI Substrate specificity and kinetic parameters of GLUT3 in rat cerebellar granule neurons SO BIOCHEMICAL JOURNAL LA English DT Article ID LIVER-TYPE GLUT2; GLUCOSE-TRANSPORT; XENOPUS OOCYTES; CYTOCHALASIN-B; ERYTHROCYTE; BRAIN; CELLS; ADIPOCYTES; FORSKOLIN; BINDING AB This study examines the apparent affinity, catalytic-centre activity ('turnover number') and stereospecificity of the neuronal glucose transporter GLUT3 in primary cultured cerebellar granule neurons. Using a novel variation of the 3-O-[C-14]methylglucose transport assay, by measuring zero-trans kinetics at 25 degrees C, GLUT3 was determined to be a high-apparent-affinity, high-activity, glucose transporter with a K-m of 2.87 +/- 0.23 mM (mean +/- S.E.M.) for 3-O-methylglucose, a V-max of 18.7 +/- 0.48 nmol/min per 10(6) cells, and a corresponding catalytic-centre activity of 853 s(-1). Transport of 3-O-methylglucose was competed by glucose, mannose, 2-deoxyglucose and galactose, but not by fructose. This methodology is compared with the more common 2-[H-3]deoxyglucose methodology and the [U-C-14]glucose transport method. The high affinity and transport activity of the neuronal glucose transporter GLUT3 appears to be an appropriate adaptation to meet the demands of neuronal metabolism at prevailing interstitial brain glucose concentrations (1-2 mM). C1 NIDDK,NIH,BETHESDA,MD 20892. NR 32 TC 82 Z9 83 U1 0 U2 2 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAY 1 PY 1996 VL 315 BP 827 EP 831 PN 3 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UK894 UT WOS:A1996UK89400019 PM 8645164 ER PT J AU Park, JB Levine, M AF Park, JB Levine, M TI Purification, cloning and expression of dehydroascorbic acid-reducing activity from human neutrophils: Identification as glutaredoxin SO BIOCHEMICAL JOURNAL LA English DT Article ID ASCORBIC-ACID; THIOLTRANSFERASE; TRANSPORT; REDUCTASE; ACCUMULATION; FIBROBLASTS; DISULFIDE; PROTEINS AB Dehydroascorbic acid-reducing activity in normal human neutrophil lysates was characterized and identified by activity-based purification and measurement of newly synthesized ascorbate by HPLC. The initial reducing activity was non-dialysable and could not be accounted for by the activity of glutathione as a reducing agent. The reducing activity was purified to homogeneity as an 11 kDa protein. The protein had a specific activity of 3 mu mol/min per mg of protein and was glutathione dependent. Kinetic experiments showed that the protein had a K-m for glutathione of 2.0 mM and a K-m for dehydroascorbic acid of 250 mu M. Dehydroascorbic acid reduction by the purified protein was pH dependent and was maximal at pH 7.5. Peptide fragments from the purified protein were analysed for amino acid sequence and the protein was identified as glutaredoxin. By using degenerate oligonucleotides based on the amino acid sequence, glutaredoxin was cloned from a human neutrophil library. Expressed purified glutaredoxin displayed reducing activity and kinetics that were indistinguishable from those of native purified enzyme. Several approaches indicated that glutaredoxin was responsible for the most of the protein-mediated dehydroascorbic acid reduction in lysates. From protein purification data, glutaredoxin was responsible for at least 47% of the initial reducing activity. Dehydroascorbic acid reduction was at least 5-fold greater in neutrophil lysates than in myeloid tumour cell lysates, and glutaredoxin was detected in normal neutrophil lysates but not in myeloid tumour cell lysates by Western blotting. Glutaredoxin inhibitors inhibited dehydroascorbic acid reduction in neutrophil lysates as much as 80%. These findings indicate that glutaredoxin plays a major role in dehydroascorbic acid reduction in normal human neutrophil lysates, and represent the first identification of dehydroascorbic acid reductase in human tissue by activity-based purification. C1 NIDDK,CELL BIOL & GENET LAB,NIH,BETHESDA,MD 20892. NR 37 TC 91 Z9 95 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAY 1 PY 1996 VL 315 BP 931 EP 938 PN 3 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UK894 UT WOS:A1996UK89400034 PM 8645179 ER PT J AU Shi, YB Wong, J PuzianowskaKuznicka, M Stolow, MA AF Shi, YB Wong, J PuzianowskaKuznicka, M Stolow, MA TI Tadpole competence and tissue-specific temporal regulation of amphibian metamorphosis: Roles of thyroid hormone and its receptors SO BIOESSAYS LA English DT Review ID I IODOTHYRONINE DEIODINASE; GENE-EXPRESSION; RETINOIC ACID; XENOPUS-LAEVIS; CONFORMATIONAL-CHANGES; BINDING; PROTEIN; INVITRO; LARVAL; LIGAND AB Amphibian metamorphosis is a post-embryonic process that systematically transforms different tissues in a tadpole. Thyroid hormone plays a causative role in this complex process by inducing a cascade of gene regulation. While natural metamorphosis does not occur until endogenous thyroid hormone has been synthesized, tadpoles are competent to respond to exogenous thyroid hormone shortly after hatching. In addition, even though the metamorphic transitions of individual organs are all controlled by thyroid hormone, each occurs at distinct developmental stages. Recent molecular studies suggest that this competence of premetamorphic tadpoles to respond to the hormone and the developmental stage-dependent regulation of tissue-specific transformations are determined in part by the levels of thyroid hormone receptors and the concentrations of cellular free thyroid hormone. In addition, at least two genes, encoding a cytosolic thyroid hormone binding protein and a 5-deiodinase, respectively, are likely to be critical players in regulating cellular free thyroid hormone concentrations. This review discusses how all of these molecular components coordinate to induce amphibian metamorphosis in a correct spatial and temporal manner. These studies provide us with general clues as to how and why tissues become competent to respond to hormonal signals. RP Shi, YB (reprint author), NICHHD,MOLEC EMBRYOL LAB,NIH,BETHESDA,MD 20892, USA. NR 63 TC 119 Z9 121 U1 3 U2 15 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0265-9247 J9 BIOESSAYS JI Bioessays PD MAY PY 1996 VL 18 IS 5 BP 391 EP 399 DI 10.1002/bies.950180509 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA UN320 UT WOS:A1996UN32000008 PM 8639162 ER PT J AU Rumsey, JM Casanova, MF Mannheim, GB Patronas, N DeVaughn, N Hamburger, SD Aquino, T AF Rumsey, JM Casanova, MF Mannheim, GB Patronas, N DeVaughn, N Hamburger, SD Aquino, T TI Corpus callosum morphology, as measured with MRI, in dyslexic men SO BIOLOGICAL PSYCHIATRY LA English DT Article DE MRI; dyslexia; corpus callosum ID DEVELOPMENTAL DYSLEXIA; MORPHOMETRIC ANALYSIS; PLANUM-TEMPORALE; RHESUS-MONKEY; HYPERACTIVITY; DISORDER; READERS; GROWTH; SEX AB To test the hypothesis of anomalous anatomy in posterior brain regions associated with language and reading, the corpus callosum was imaged in the midsagittal plane with magnetic resonance, The areas of the anterior, middle, and posterior segments were measured in 21 dyslexic men (mean age 27 yrs, SD 6) and in 19 matched controls. As predicted the area of the posterior third of the corpus callosum, roughly equivalent to the isthmus and splenium, was larger in dyslexic men than in controls, No differences were seen in the anterior or middle corpus callosum. The increased area of the posterior corpus callosum may reflect anatomical variation associated with deficient lateralization of function in posterior language regions of the cortex and their right-sided homologues, hypothesized to differ in patients with dyslexia. C1 MED COLL GEORGIA, DEPT PSYCHIAT & HLTH BEHAV, AUGUSTA, GA 30912 USA. NIH, CTR CLIN, BETHESDA, MD 20892 USA. RP Rumsey, JM (reprint author), NIMH, CHILD PSYCHIAT BRANCH, BLDG 10, ROOM 6N240, BETHESDA, MD 20892 USA. NR 44 TC 64 Z9 65 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1996 VL 39 IS 9 BP 769 EP 775 DI 10.1016/0006-3223(95)00225-1 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UJ630 UT WOS:A1996UJ63000003 PM 8731517 ER PT J AU Robbins, CM Hsu, E Gillevet, PM AF Robbins, CM Hsu, E Gillevet, PM TI Sequencing homopolymer tracts and repetitive elements SO BIOTECHNIQUES LA English DT Article ID DNA C1 NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NR 5 TC 13 Z9 13 U1 0 U2 1 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD MAY PY 1996 VL 20 IS 5 BP 862 EP & PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UJ638 UT WOS:A1996UJ63800026 PM 8723932 ER PT J AU Apel, WS AF Apel, WS TI Gel-Pro Analyzer 1.0 SO BIOTECHNOLOGY SOFTWARE & INTERNET JOURNAL LA English DT Software Review C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1088-4270 J9 BIOTECHNOL SOFTW I J JI Biotechnol. Softw. Internet J. PD MAY-JUN PY 1996 VL 13 IS 3 BP 6 EP 10 PG 5 WC Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications SC Biotechnology & Applied Microbiology; Computer Science GA WC839 UT WOS:A1996WC83900001 ER PT J AU Weiler, SR Mou, S DeBerry, CS Keller, JR Ruscetti, FW Ferris, DK Longo, DL Linnekin, D AF Weiler, SR Mou, S DeBerry, CS Keller, JR Ruscetti, FW Ferris, DK Longo, DL Linnekin, D TI JAK2 is associated with the c-kit proto-oncogene product and is phosphorylated in response to stem cell factor SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; SIGNAL-TRANSDUCTION; TYROSINE KINASES; GROWTH-FACTOR; ERYTHROPOIETIN RECEPTOR; ACTIVATION; INTERLEUKIN-3; FAMILY; DOMAIN AB Stem cell factor (SCF) is a hematopoietic growth factor that interacts with the receptor tyrosine kinase, c-kit. We have found that SCF stimulates rapid and transient tyrosine phosphorylation of JAK2 in human and murine cell lines, as well as in normal human progenitor cells, JAK2 and c-kit were associated in unstimulated cells with further recruitment of JAK2 to the c-kit receptor complex after SCF stimulation. Treatment of cells with JAK2 antisense oligonucleotides resulted in a 46% decrease in SCF-induced proliferation. These data demonstrate that SCF induces tyrosine phosphorylation of JAK2 and suggest that JAK2 is a component of the SCF signal transduction pathway. This is a US government work. There are no restrictions on its use. C1 NCI,LAB LEUKOCYTE BIOL,BIOL RESPONSE MODIFIERS PROGRAM,DIV CANC TREATMENT,FREDERICK,MD 21702. NCI,BIOL CARCINOGENESIS & DEV PROGRAM,SAIC FREDERICK,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. NR 31 TC 88 Z9 89 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 1996 VL 87 IS 9 BP 3688 EP 3693 PG 6 WC Hematology SC Hematology GA UH142 UT WOS:A1996UH14200019 PM 8611693 ER PT J AU Bergan, R Neckers, L AF Bergan, R Neckers, L TI How do antisense oligodeoxynucleotides inhibit the growth of chronic myelogenous leukemia cells? SO BLOOD LA English DT Letter ID DNA RP Bergan, R (reprint author), NCI,CLIN PHARMACOL BRANCH,NIH,BETHESDA,MD 20892, USA. NR 8 TC 3 Z9 3 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 1996 VL 87 IS 9 BP 4019 EP 4019 PG 1 WC Hematology SC Hematology GA UH142 UT WOS:A1996UH14200068 PM 8611740 ER PT J AU Tanaka, H Barnes, J Liang, CT AF Tanaka, H Barnes, J Liang, CT TI Effect of age on the expression of insulin-like growth factor-I, interleukin-6, and transforming growth factor-beta mRNAs in rat femurs following marrow ablation SO BONE LA English DT Article DE gene expression; IGF-I; TGF-beta; aging; femur ID COLLAGEN-SYNTHESIS; RIBONUCLEIC-ACIDS; OSTEOGENIC CELLS; BONE-FORMATION; INVITRO; COMPLEMENTARY; HORMONE; INVIVO AB The expression of insulin-like growth factor-I (IGF-I), interleukin-6 (IL-6), and transforming growth factor-beta(1) (TGF-beta(1)) mRNA in rat femurs was examined following marrow ablation, Northern blot analysis showed multiple transcripts of IGF-I, a major transcript of 1.3 kb and a minor one of 2.4 kb for IL-6 and a single band of 2.5 kb for TGF-beta(1), respectively, Examination of the temporal activation pattern showed IGF-I expression peaked at day 3 (150% over the basal level) after injury and preceded the maximal expression of procollagen alpha(1)(I), osteopontin, alkaline phosphatase, and osteocalcin mRNAs, This suggests that IGF-I is involved mainly in osteoblast development and bone formation, In contrast, IL-6 expression was elevated between days 3 and 9 (45-60% over the basal level), The sustained elevation of IL-6 expression at day 9 is consistent with the role for this cytokine in the development of osteoclasts and bone resorption, The expression of TGF-beta(1) was not altered up to day 9 after marrow ablation, While the temporal expression patterns of IGF-I and IL-6 mRNA did not differ between adult and old rats, the maximal level of IGF-I mRNA at day 3 was 72% higher in adult as compared to old bones, In contrast, the peak level of IL-6 mRNA at days 6-9 was 45% higher in old as compared to adult bones, Although the level of TGF-beta(1) mRNA did not change following marrow ablation, levels of TGF-beta(1) were consistently higher in old rats, Our results suggest that the impaired bone formation and elevated bone resorption in aged animals may be due in part to the reduced expression of IGF-I and an overexpression of IL-6 in old bone. C1 NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. NR 38 TC 33 Z9 37 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 8756-3282 J9 BONE JI Bone PD MAY PY 1996 VL 18 IS 5 BP 473 EP 478 DI 10.1016/8756-3282(96)00041-5 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UJ627 UT WOS:A1996UJ62700011 PM 8739906 ER PT J AU Mavroudis, DA Jiang, YZ Hensel, N Lewalle, P Couriel, D Kreitman, RJ Pastan, I Barrett, AJ AF Mavroudis, DA Jiang, YZ Hensel, N Lewalle, P Couriel, D Kreitman, RJ Pastan, I Barrett, AJ TI Specific depletion of alloreactivity against haplotype mismatched related individuals by a recombinant immunotoxin: A new approach to graft-versus-host disease prophylaxis in haploidentical bone marrow transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article DE specific depletion; alloreactivity; immunotoxin; GVHD; haploidentical ID T-CELL DEPLETION; PSEUDOMONAS EXOTOXIN; LEUKEMIA; DONORS; CHAIN; RECOVERY; RECEPTOR; BEARING AB Haploidentical bone marrow transplantation (BMT) is associated with a high risk of severe graft-versus-host disease (GVHD), While pan-T cell depletion of the graft is the most effective means of preventing severe GVHD, it is associated with delayed recovery of T cell function leading to fatal infections, We used two related Pseudomonas exotoxin-based immunotoxins, anti-Tac(Fv)-PE38 and anti-Tac(Fv)-PE38KDEL, that both target the IL-2 receptor on activated T cells, to specifically deplete alloreactive lymphocytes against haploidentical stimulators, The functional capacity of the remaining lymphocytes was tested in proliferative assays against the original haploidentical stimulator and pooled cells from other mismatched donors (third party), We varied the recombinant toxin concentration and schedule to determine the optimum conditions for selective depletion, In 10 experiments, the mean residual reactivity after depletion was 7.6 +/- 1.4% against the haploidentical stimulator and 64.2 +/- 5% against the third party, expressed as a percentage of the undepleted response to the same stimulators, Depletion was shown to be specific for mixed lymphocyte culture (MLC)-activated lymphocytes, The immunotoxin did not affect CFU-GM growth of normal BM cells, This selective depletion of haploidentical alloreactivity could be used to prevent GVHD while conserving immune recovery following haploidentical BMT. C1 NCI,MOLEC BIOL LAB,DIV CANC BIOL & DIAG,NIH,BETHESDA,MD 20892. RP Mavroudis, DA (reprint author), NHLBI,BONE MARROW TRANSPLANTAT UNIT,NIH,HEMATOL BRANCH,BLDG 10,RM7C103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 34 TC 60 Z9 60 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAY PY 1996 VL 17 IS 5 BP 793 EP 799 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA UK314 UT WOS:A1996UK31400021 PM 8733700 ER PT J AU Weiss, HA Brinton, LA Brogan, D Coates, RJ Gammon, MD Malone, DE Schoenberg, JB Swanson, CA AF Weiss, HA Brinton, LA Brogan, D Coates, RJ Gammon, MD Malone, DE Schoenberg, JB Swanson, CA TI Epidemiology of in situ and invasive breast cancer in women aged under 45 SO BRITISH JOURNAL OF CANCER LA English DT Article DE breast cancer; carcinoma in situ; invasive breast cancer; epidemiology; premenopausal ID ORAL-CONTRACEPTIVE USE; ALCOHOL-CONSUMPTION; RISK; CARCINOMA AB The incidence of in situ breast cancer in the USA has increased rapidly in recent years, even among young women. A population-based case-control study of 1616 breast cancer cases aged under 45 in the USA was used to examine risk factors for in situ, local and regional distant tumours. Almost 60% of in situ tumours were detected by routine mammograms compared with 18% of local rumours and 8% of regional/distant tumours. After adjustment for screening history and established risk factors, family history of breast cancer in a first-degree relative and African-American race were associated with an increased risk of all stages of breast cancer. The associations with nulliparity. a previous breast biopsy and body mass index were significantly stronger for in situ tumours than for local or regional distant disease. Alcohol consumption was associated with an increasing trend in risk of regional distant rumours but not of earlier stage rumours, indicating that alcohol may be involved in late-stage events. Analyses by histological type of in situ tumours suggested that both ductal and lobular carcinoma in situ were associated with most established breast cancer risk factors, and the magnitude of association tended to be greater for the ductal form. C1 EMORY UNIV,ROLLINS SCH PUBL HLTH,DEPT BIOSTAT,ATLANTA,GA 30322. EMORY UNIV,ROLLINS SCH PUBL HLTH,DEPT EPIDEMIOL,ATLANTA,GA 30322. COLUMBIA UNIV,SCH PUBL HLTH,DIV EPIDEMIOL,NEW YORK,NY 10032. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. NEW JERSEY STATE DEPT HLTH,SPECIAL EPIDEMIOL PROGRAM,TRENTON,NJ 08625. RP Weiss, HA (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EXECUT PLAZA N,ROOM 443,6130 EXEC BLVD,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 37 TC 82 Z9 83 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAY PY 1996 VL 73 IS 10 BP 1298 EP 1305 DI 10.1038/bjc.1996.248 PG 8 WC Oncology SC Oncology GA UK323 UT WOS:A1996UK32300025 PM 8630296 ER PT J AU Litman, RE Su, TP Potter, WZ Hong, WW Pickar, D AF Litman, RE Su, TP Potter, WZ Hong, WW Pickar, D TI Idazoxan and response to typical neuroleptics in treatment-resistant schizophrenia - Comparison with the atypical neuroleptic, clozapine SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID PLASMA; FLUPHENAZINE; CATECHOLAMINES; ANTAGONIST AB Background. We investigated whether antagonism of alpha(2) adrenergic receptors would augment treatment response in schizophrenia, by administering idazoxan, an alpha(2) antagonist drug, to treatment-resistant patients on typical neuroleptics. Method, Seventeen hospitalised treatment-resistant patients with DSM-III-R schizophrenia or schizoaffective disorder were studied on typical neuroleptic treatment, on treatment with idazoxan plus typical neuroleptic, and after discontinuation of idazoxan, in fixed, non-random order, and under double-blind, placebo-controlled conditions. Results. The addition of idazoxan to fluphenazine treatment resulted in significant reductions of global psychosis and total, positive and negative symptoms on the Brief Psychiatric Rating Scale. compared to neuroleptic treatment alone. Symptom improvement significantly correlated with idazoxan-induced changes in indices of noradrenergic function. In a subgroup of patients, idazoxan plus typical neuroleptic treatment compared favourably with clozapine treatment, when both were compared to typical neuroleptic treatment alone. Conclusions. The antagonism of alpha(2) receptors augmented therapeutic response to typical neuroleptic treatment in treatment-resistant patients with schizophrenia. This antagonism may contribute to clozapine's superior antipsychotic effects. RP Litman, RE (reprint author), NIMH,EXPTL THERAPEUT BRANCH,SECT CLIN STUDIES,NIH,10-4N212,10 CTR DR,MSC 1380,BETHESDA,MD 20892, USA. NR 26 TC 102 Z9 106 U1 0 U2 0 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON, ENGLAND SW1X 8PG SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD MAY PY 1996 VL 168 IS 5 BP 571 EP 579 DI 10.1192/bjp.168.5.571 PG 9 WC Psychiatry SC Psychiatry GA UJ345 UT WOS:A1996UJ34500008 PM 8733795 ER PT J AU Skrtic, D Eidelman, N Golomb, G Breuer, E Eanes, ED AF Skrtic, D Eidelman, N Golomb, G Breuer, E Eanes, ED TI In vitro inhibition of membrane-mediated calcification by novel phosphonates SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE geminal bisphosphonates; bone disorders; hydroxyapatite; calcium metabolism disorders ID AQUEOUS SUSPENSIONS; CALCIUM PHOSPHATES; HYDROXYAPATITE; LIPOSOMES; DIPHOSPHONATES; CRYSTALS; VESICLES; INVITRO; BINDING; INVIVO AB The effects of a series of novel phosphonates on the kinetics of mineral development in an ionophore-primed 7:2:1 phosphatidylcholine (PC): dicetylphosphate (DCP): cholesterol (Chol) liposomal model system are reported. When present at 2.5 mu mol/liter or 25 mu mol/liter concentrations in the solution surrounding the liposomes, the investigated phosphonates did not significantly delay the initial formation of hydroxyapatite-like calcium phosphate salts (HAP) within the liposomes or the penetration of HAP crystals through the enclosing membranes. However, the phosphonates variably retarded the subsequent growth and proliferation of the HAP crystals once they became directly exposed to the phosphonate-containing solution. The effectiveness of phosphonates in inhibiting extraliposomal precipitation strongly depended on their structure. The inhibitory action on active surface growth sites of released intraliposomal crystals was found to be the most effective if the phosphonate molecule contained two phosphonic groups Linked to the same C atom. At a phosphonate concentration of 25 mu mol/liter, the following general order of effectiveness was established: geminal bisphosphonate greater than or equal to geminal tetrakisphosphonate > bisacylphosphonates > monoacylphosphonate > bisalkylphosphonate. Within the bisacylphosphonate family, the highest inhibitory action was observed when four or five -CH2- groups separated the ketophosphonic groups. C1 NATL INST STAND & TECHNOL,NIDR,BONE RES BRANCH,ASSOCIATE PROGRAM,GAITHERSBURG,MD 20899. NATL INST STAND & TECHNOL,AMER DENT ASSOC HLTH FDN,PAFFENBARGER RES CTR,GAITHERSBURG,MD 20899. RUDJER BOSKOVIC INST,DEPT CHEM,ZAGREB 41000,CROATIA. HEBREW UNIV JERUSALEM,SCH PHARM,DEPT PHARM,IL-91120 JERUSALEM,ISRAEL. HEBREW UNIV JERUSALEM,SCH PHARM,DEPT PHARMACEUT CHEM,IL-91120 JERUSALEM,ISRAEL. RI Breuer, Eli/E-8382-2011; OI Golomb, Gershon/0000-0002-7369-9831 FU NHLBI NIH HHS [HL 30035] NR 34 TC 13 Z9 14 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD MAY PY 1996 VL 58 IS 5 BP 347 EP 354 DI 10.1007/BF02509384 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UJ247 UT WOS:A1996UJ24700009 PM 8661970 ER PT J AU Brouwers, P Mohr, E Hildebrand, K Hendricks, M Claus, JJ Baron, IS Young, M Pierce, P AF Brouwers, P Mohr, E Hildebrand, K Hendricks, M Claus, JJ Baron, IS Young, M Pierce, P TI A novel approach to the determination and characterization of HIV dementia SO CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS-RELATED COMPLEX; NEUROLOGICAL DISEASE; ZIDOVUDINE AZT; REACTION-TIME; INFECTION; BRAIN; CHILDREN; ENCEPHALOPATHY; ABNORMALITIES AB Background: Neuropsychological studies of the pattern and extent of cognitive impairment in HIV-infected patients have mostly used deviations from control values and/or cut-off scores as criteria for classification of dementia. There is, however, no agreement as to how to define impairment, and classification is imprecise. Method: The current study used a dementia classification matrix, developed with a step-wise linear discriminant analysis of neuropsychological data from patients with primary neurodegenerative dementias, to classify symptomatic HIV patients as demented or non-demented, and furher to differentiate cortical and subcortical dementia patterns. Thirty-two male and 2 female patients (mean age 39 +/- 2) with symptomatic HIV disease (mean absolute Cd4 count 195 +/- 41) participated in the study. Results: Thirty-fie per cent of patients were classified as demented. Of these, 83% showed a subcortical pattern and 17% a cortical profile of deficits. Significant differences between patients classified as subcortically demented and those categorized as normal on neuropsychological measures associated with subcortical integrity further validated the classification. Measures of psychiatric status between subgroups were similar. Conclusion: Since certain treatments may delay or reverse cognitive deficits, the use of an objective classification method based on discriminant analysis may help to identify patients who may benefit from therapy. C1 NINCDS,BETHESDA,MD 20892. UNIV OTTAWA,FAC MED,OTTAWA,ON,CANADA. GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. RP Brouwers, P (reprint author), NCI,PEDIAT BRANCH,NIH,CTR CLIN,BLDG 10,RM 13N240,BETHESDA,MD 20892, USA. NR 59 TC 7 Z9 8 U1 0 U2 0 PU CANADIAN J NEUROL SCI INC PI CALGARY PA PO BOX 4220, STATION C EDITORIAL & SUBSCRIPTION SERV, CALGARY AB T2T 5N1, CANADA SN 0317-1671 J9 CAN J NEUROL SCI JI Can. J. Neurol. Sci. PD MAY PY 1996 VL 23 IS 2 BP 104 EP 109 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA UN402 UT WOS:A1996UN40200004 PM 8738921 ER PT J AU Risinger, JI Barrett, JC Watson, P Lynch, HT Boyd, J AF Risinger, JI Barrett, JC Watson, P Lynch, HT Boyd, J TI Molecular genetic evidence of the occurrence of breast cancer as an integral tumor in patients with the hereditary nonpolyposis colorectal carcinoma syndrome SO CANCER LA English DT Article DE hereditary nonpolyposis colorectal cancer; breast cancer; microsatellite instability; mismatch repair; DNA repair; hMLH1; colon cancer; hereditary; Lynch syndrome II ID LYNCH SYNDROME-II; FAMILY HISTORY; INSTABILITY; MUTATIONS; SPECTRUM; RISK; KINDREDS; HOMOLOG; COLON AB BACKGROUND. The hereditary nonpolyposis colorectal carcinoma (HNPCC) syndrome is an autosomal dominant genetic disorder caused by the inheritance of a mutation in one of a family of genes encoding DNA mismatch repair (MMR) proteins. HNPCC manifests as genetic instability in linked tumors. Clinically, the syndrome is characterized by early onset malignancies, primarily of the colon and endometrium, with an increased incidence of tumors at other gastrointestinal Sites, upper urologic tract, ovary, and pancreas as well. However, the inclusion of breast cancer as an integral tumor of this syndrome is controversial. METHODS. Mutation screening of MMR genes was carried out by single strand conformation polymorphism (SSCP) and sequencing analyses of genomic DNA prepared from normal lymphocytes. Expression analysis was performed by SSCP. Sequence analyses of cDNA was prepared from breast tumor tissue and normal lymphocytes. Genetic instability was assessed by comparing the electrophoretic mobility of polymerase chain reaction (PCR) products using multiple microsatellite markers. RESULTS. A 4-bp frameshift mutation in the hMLH1 gene was found to segregate with disease in the germlines of the affected members of a large kindred HNPCC. Expression of only the mutant allele was observed in the breast cancer tissue of one family member, however both alleles were observed in her normal tissue. This breast cancer exhibited widespread microsatellite instability, as did breast cancers obtained from several other HNTPCC kindreds. CONCLUSIONS. These data indicate that breast cancer may result from the inheritance of a mutant MMR gene, and that breast cancer may occur as an integral tumor in the HNPCC syndrome. (C) 1996 American Cancer Society. C1 UNIV PENN,MED CTR,DEPT OBSTET & GYNECOL,DIV GYNECOL ONCOL,PHILADELPHIA,PA 19104. NIEHS,MOLEC CARCINOGENESIS LAB,NIH,CHAPEL HILL,NC. UNIV N CAROLINA,CURRICULUM GENET & MOLEC BIOL,CHAPEL HILL,NC. CREIGHTON UNIV,DEPT PREVENT MED & PUBL HLTH,OMAHA,NE 68178. NR 49 TC 103 Z9 105 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD MAY 1 PY 1996 VL 77 IS 9 BP 1836 EP 1843 DI 10.1002/(SICI)1097-0142(19960501)77:9<1836::AID-CNCR12>3.0.CO;2-0 PG 8 WC Oncology SC Oncology GA UF719 UT WOS:A1996UF71900012 PM 8646682 ER PT J AU Coates, RJ Click, LA Harlan, LC Robboy, S Barrett, RJ Eley, JW Reynolds, P Chen, VW Darity, WA Blacklow, RS Edwards, BK AF Coates, RJ Click, LA Harlan, LC Robboy, S Barrett, RJ Eley, JW Reynolds, P Chen, VW Darity, WA Blacklow, RS Edwards, BK TI Differences between black and white patients with cancer of the uterine corpus in interval from symptom recognition to initial medical consultation (United states) SO CANCER CAUSES & CONTROL LA English DT Article DE blacks; health behavior; health services accessibility; race; United States; uterine neoplasms; women ID BREAST-CANCER; SEEKING CARE; DELAY; STAGE; DIAGNOSIS; SURVIVAL; DISEASE; DETERMINANTS; WOMEN AB To determine whether Black women with symptoms of uterine corpus cancer had longer times from symptom recognition to initial medical consultation than did White women in the United States, 331 newly diagnosed patients living in Atlanta (GA), New Orleans (LA), and San Francisco/Oakland (CA) during 1985-87 were interviewed to collect information on symptoms, dates of recognition and consultation, and other factors that might affect the interval. Data were analyzed to estimate medical consultation rates and rate ratios following symptom recognition. Median recalled times between symptom recognition and consultation were 16 days for Black women and 14 days for White women. Although poverty, having no usual source of healthcare, and other factors were associated with lower consultation rates, the adjusted rate among Black women was only somewhat lower (0.87) than among White women, and the 95 percent confidence interval (CI = 0.58-1.31) was consistent with no true difference between the races. In addition, the median time to consultation for women with stage IV cancer was only 15 days longer than the time (14 days) for the women with stage I cancer. These results suggest that time from symptom recognition to initial medical consultation does not contribute importantly to the more advanced stage cancer of the uterine corpus commonly found among Black women. C1 NCI,DIV CANC PREVENT & CONTROL,ROCKVILLE,MD. DUKE UNIV,MED CTR,DEPT PATHOL OBSTET & GYNECOL,DURHAM,NC. CALIF DEPT HLTH SERV,ENVIRONM EPIDEMIOL SECT,EMERYVILLE,CA. LOUISIANA STATE UNIV,MED CTR,DEPT PATHOL,NEW ORLEANS,LA 70112. UNIV MASSACHUSETTS,SCH PUBL HLTH,AMHERST,MA 01003. NE OHIO UNIV,COLL MED,OFF PRESIDENT,ROOTSTOWN,OH 44272. RP Coates, RJ (reprint author), EMORY UNIV,ROLLINS SCH PUBL HLTH,DEPT EPIDEMIOL,1518 CLIFTON RD NE,ATLANTA,GA 30322, USA. FU NCI NIH HHS [N01CN-35042-46, N01CN-45174, N01CN-05227] NR 37 TC 14 Z9 14 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 1996 VL 7 IS 3 BP 328 EP 336 DI 10.1007/BF00052938 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA UL406 UT WOS:A1996UL40600006 PM 8734826 ER PT J AU Wargovich, MJ Chen, CD Jimenez, A Steele, VE Velasco, M Stephens, LC Price, R Gray, K Kelloff, GJ AF Wargovich, MJ Chen, CD Jimenez, A Steele, VE Velasco, M Stephens, LC Price, R Gray, K Kelloff, GJ TI Aberrant crypts as a biomarker for colon cancer: Evaluation of potential chemopreventive agents in the rat SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID MALE F344 RATS; ORGANOSULFUR COMPOUNDS; PRENEOPLASTIC LESIONS; DIETARY CURCUMIN; MURINE COLON; CARCINOGENESIS; AZOXYMETHANE; INHIBITION; NEOPLASIA; FOCI AB We assessed the effects of 41 potential chemopreventive agents in the F344 rat using the inhibition of carcinogen-induced aberrant crypt foci (ACF) in the colon as the measure of efficacy. ACF were induced by the carcinogen azoxymethane in F344 rats by two sequential weekly injections at a dose of 15 mg/kg. Two weeks after the last azoxymethane injection, animals were evaluated for the number of aberrant crypts detected in methylene blue-stained whole mounts of rat colon. The 41 agents were derived from a priority listing that was based on reports of chemopreventive activity in the literature and/or efficacy data from in vitro models of carcinogenesis. The list of agents included representative examples of phytochemicals, vitamins, minerals, inhibitors of proliferation, inducers of Phase 1 and Phase 2 metabolism systems, nonsteroidal anti-inflammatory agents, and differentiation agents. Eighteen agents were positive in the assay, significantly reducing the incidence of ACF at least in one of two doses tested. As a chemical class, the nonsteroidal anti-inflammatory drugs, which included ibuprofen, ketoprofen, piroxicam, and indomethacin, were most active; other less potent agents were arginine, butylated hydroxyanisole, curcumin, diallyl sulfide, difluoromethylornithine, 18 beta-glycyrrhetinic acid, indole-3-carbinol, oltipraz, purpurin, rutin, and the sodium salts of butyrate, selenite, and thiosulfate. Twenty-three agents did not inhibit ACF; included among these were several agents that promoted the development of ACF at one or both doses tested: benzyl isothiocyanate, calcium glucarate, catechin, dihydroepiandosterone, fluocinolone acetonide, folic acid, levamisole, 2-mercaptoethanesulfonic acid, nordihydroguiaretic acid, potassium glucarate, propyl gallate, beta-sitosterol, sodium cromolyn, sodium molybdate, and sulfasalazine. The aberrant crypt assay demonstrates reasonable specificity and sensitivity in predicting which agents are likely to prevent colon cancer. C1 UNIV TEXAS, MD ANDERSON CANC CTR, DIV VET MED & SURG, HOUSTON, TX 77030 USA. NCI, DIV CANC PREVENT & CONTROL, CHEMOPREVENT BRANCH, BETHESDA, MD 20892 USA. RP Wargovich, MJ (reprint author), UNIV TEXAS, MD ANDERSON CANC CTR, DEPT GASTROINTESTINAL MED ONCOL & DIGEST DIS, BOX 78, HOUSTON, TX 77030 USA. FU NCI NIH HHS [CA-16672] NR 53 TC 166 Z9 169 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 1996 VL 5 IS 5 BP 355 EP 360 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA UJ727 UT WOS:A1996UJ72700006 PM 9162301 ER PT J AU Schatzkin, A Lanza, E Freedman, LS Tangrea, J Cooper, MR Marshall, JR Murphy, PA Selby, JV Shike, M Schade, RR Burt, W Kikendall, JW Cahill, J AF Schatzkin, A Lanza, E Freedman, LS Tangrea, J Cooper, MR Marshall, JR Murphy, PA Selby, JV Shike, M Schade, RR Burt, W Kikendall, JW Cahill, J TI The Polyp Prevention Trial I: Rationale, design, recruitment, and baseline participant characteristics SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID COLON CANCER; COLORECTAL-CANCER; DIETARY FIBER; EPIDEMIOLOGIC EVIDENCE; ADENOMATOUS POLYPS; UNITED-STATES; RISK; CARCINOGENESIS; SURVEILLANCE; MORTALITY AB The Polyp Prevention Trial (PPT) is a multicenter randomized controlled trial examining the effect of a low-fat (20% of total energy intake), high-fiber (18 g/1000 kcal), high-vegetable and -fruit (5-8 daily servings) dietary pattern on the recurrence of adenomatous polyps of the large bowel, precursors of most colorectal malignancies. Eligibility criteria include one or more adenomas removed within 6 months of randomization; complete nonsurgical polyp removal and complete colonic examination to the cecum at the qualifying colonoscopy; age 35 years or more; no history of colorectal cancer, inflammatory bowel disease, or large bowel resection; and satisfactory completion of a food frequency questionnaire and 4-day food record. Of approximately 38,277 potential participants with one or more polyps recently resected, investigators at eight clinical centers randomized 2,079 (5.4%; 1,037 in the intervention and 1,042 in the control arm) between June 1991 and January 1994, making the PPT the largest adenoma recurrence trial ever conducted. Of PPT participants, 35% are women and 10% are minorities. At study entry, participants averaged 61.4 Sears of age; 14% of them smoked, and 22% used aspirin. At the baseline colonoscopy, 35% of participants had two or more adenomas, and 29% had at least one large (greater than or equal to 1 cm) adenoma. Demographic, behavioral, dietary, and clinical characteristics are comparable across the two study arms. Participants have repeat colonoscopies after 1 (T-1) and 4 (T-4) years of follow-up. The primary end point is adenoma recurrence; secondary end points include number, size, location, and histology of adenomas. All resected lesions are reviewed centrally by gastrointestinal pathologists. The trial provides 90% power to detect a reduction of 24% in the annual adenoma recurrence rate. The primary analytic period, on which sample size calculations were based, is 3 years (T-1 to T-4), which permits a 1-year lag time for the intervention to work and allows a more definitive clearing of lesions at T-1, given that at least 10-15% of polyps may be missed at baseline, The final (T-4) colonoscopies are expected to be completed in early 1998. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. SUNY BUFFALO,SCH MED & BIOMED SCI,BUFFALO,NY. US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,HINES,IL 60141. KAISER FDN RES INST,OAKLAND,CA. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. UNIV PITTSBURGH,PITTSBURGH,PA. UNIV UTAH,SALT LAKE CITY,UT. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. WESTAT CORP,ROCKVILLE,MD. RP Schatzkin, A (reprint author), NCI,DEPT HLTH & HUMAN SERV,PUBL HLTH SERV,NIH,BETHESDA,MD 20892, USA. NR 50 TC 82 Z9 84 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 1996 VL 5 IS 5 BP 375 EP 383 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA UJ727 UT WOS:A1996UJ72700009 PM 9162304 ER PT J AU Sanford, KK Parshad, R Price, FM Tarone, RE Benedict, WF AF Sanford, KK Parshad, R Price, FM Tarone, RE Benedict, WF TI Cytogenetic responses to G(2) phase x-irradiation of cells from retinoblastoma patients SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID ABERRATION PRODUCTION; CHROMATID DAMAGE; DNA-REPAIR; CANCER; RADIOSENSITIVITY; FIBROBLASTS; RADIATION; PREDISPOSITION; HOMOZYGOSITY; LYMPHOCYTES AB Fibroblast cell lines from 20 retinoblastoma (RB) patients with the hereditary bilateral form of disease compared with 16 lines from normal donors had a significantly higher chromatid aberration frequency (CAF), and more displaced and nondisplaced breaks per 100 metaphase cells after x-irradiation during the G(2) phase of the cell cycle. The mean CAF was 39 +/- 1.0, range 30-46, for cells from normal subjects, compared to a mean of 245.6, range 101-506, for cells from hereditary RB patients (p < 10(-6)). Of fibroblast lines from eight patients with unilateral RB, four had a CAF comparable to that of lines from normal donors (< 60) and four had a high CAF (> 130), resembling that of hereditary forms; two of the latter four lines were from patients with familial or deletion 13 forms of RB. Furthermore, in two families, PHA-stimulated blood lymphocytes from RB patients, one bilateral and one unilateral, and from certain unaffected first-degree relatives after G(2) phase X-irradiation had a high CAF (greater than or equal to 110) compared to a CAF (greater than or equal to 53) of cells from three normal donors sampled at the same time. These results were shown not to be related to differences in cell cycle progression or initial extent of chromatid damage. The results suggest that the high frequency of chromatid aberrations in the cells from hereditary RB patients results from a genetic deficiency in DNA repair. C1 NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. HOWARD UNIV,COLL MED,DEPT PATHOL,WASHINGTON,DC. BAYLOR COLL MED,CTR BIOTECHNOL,THE WOODLANDS,TX 77381. RP Sanford, KK (reprint author), NCI,CELLULAR & MOLEC BIOL LAB,RM 2D15,BLDG 37,BETHESDA,MD 20892, USA. FU NEI NIH HHS [EYO-6195] NR 35 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD MAY PY 1996 VL 88 IS 1 BP 43 EP 48 DI 10.1016/0165-4608(95)00279-0 PG 6 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA UL706 UT WOS:A1996UL70600008 PM 8630978 ER PT J AU Zhuang, ZP Vortmeyer, AO Mark, EJ Odze, R EmmertBuck, MR Merino, MJ Moon, H Liotta, LA Duray, PH AF Zhuang, ZP Vortmeyer, AO Mark, EJ Odze, R EmmertBuck, MR Merino, MJ Moon, H Liotta, LA Duray, PH TI Barrett's esophagus: Metaplastic cells with loss of heterozygosity at the APC gene locus are clonal precursors to invasive adenocarcinoma SO CANCER RESEARCH LA English DT Article ID CANCERS; AMPLIFICATION; DYSPLASIA; RECEPTOR; HST-1; RISK; P53 AB Adenocarcinoma in Barrett's esophagus is the second most rapidly increasing cancer in western society, The cause and pathogenesis are unknown, Although histological studies suggest that there is successive progression from metaplasia and dysplasia, with a high risk of subsequent invasive carcinoma, at present there is no direct evidence that metaplastic and dysplastic epithelia are clonal precursors of adenocarcinoma, We selected 12 esophagectomy specimens of Barrett's esophagus patients, which showed a spectrum of normal tissue, metaplasia, dysplasia, and invasive adenocarcinoma in each individual biopsy, We applied the microdissection technique to selectively procure microscopic tissue samples from H&E-stained slides for genetic evaluation using polymorphic markers flanking the APC gene locus, Identical APC gene alterations were found in the dysplastic and adenocarcinoma foci of all informative cases, The same changes were observed even in some metaplastic foci adjacent to dysplasia, Furthermore, clonality analysis of X-chromosome inactivation in female cases verified the same X-chromosome inactivation pattern in carcinoma, dysplasia, and metaplasia adjacent to dysplasia, No APC gene alterations were found in the normal epithelium and metaplasia distant from dysplasia, These data show for the first time that a tissue field of genotypic changes precedes the histopathological phenotypic changes of carcinoma in Barrett's esophagus syndrome, Our findings, in conjunction with the applied tissue microdissection technique, may help identify genotypic changes in patients with Barrett's esophagus before phenotypic changes occur, Therefore, genotyping of Barrett's metaplastic epithelium may supplement the histopathological evaluation of Barrett's esophagus. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. CATHOLIC UNIV SEOUL,MED COLL,SEOUL,SOUTH KOREA. NR 27 TC 88 Z9 90 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1996 VL 56 IS 9 BP 1961 EP 1964 PG 4 WC Oncology SC Oncology GA UG756 UT WOS:A1996UG75600002 PM 8616831 ER PT J AU Yoshiji, H Gomez, DE Shibuya, M Thorgeirsson, UP AF Yoshiji, H Gomez, DE Shibuya, M Thorgeirsson, UP TI Expression of vascular endothelial growth factor, its receptor, and other angiogenic factors in human breast cancer SO CANCER RESEARCH LA English DT Article ID PERMEABILITY FACTOR; HUMAN GLIOMAS; FACTOR-ALPHA; FACTOR-BETA; CELLS; MITOGEN; GELS AB Angiogenesis is essential for the growth and metastasis of solid tumors, In this study, we examined gene expression of vascular endothelial growth factor (VEGF); its receptor, flt-1; basic fibroblast growth factor; and transforming growth factors (TGFs) alpha and beta in 18 paired cases of human breast carcinomas and the adjacent nonneoplastic tissues, In all of the paired cases, VEGF expression was markedly increased in the carcinomas, In contrast, an insignificant difference was observed in the expression of flt-1, basic fibroblast growth factor, TGF-alpha, and TGF-beta between the malignant breast tissue and the nonneoplastic counterpart. Immunostaining showed variable VEGF positivity of the malignant cells, whereas the nonneoplastic breast epithelial cells were negative, The findings of this study suggest that VEGF is an important angiogenic factor in human breast cancer. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,TUMOR BIOL & CARCINOGENESIS SECT,DIV BASIC SCI,BETHESDA,MD 20892. UNIV TOKYO,INST MED SCI,DEPT GENET,MINATO KU,TOKYO 108,JAPAN. OI Gomez, Daniel E/0000-0002-8629-0787 NR 36 TC 277 Z9 295 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1996 VL 56 IS 9 BP 2013 EP 2016 PG 4 WC Oncology SC Oncology GA UG756 UT WOS:A1996UG75600013 PM 8616842 ER PT J AU Schold, SC Kokkinakis, DM Rudy, JL Moschel, RC Pegg, AE AF Schold, SC Kokkinakis, DM Rudy, JL Moschel, RC Pegg, AE TI Treatment of human brain tumor xenografts with O-6-benzyl-2'-deoxyguanosine and BCNU SO CANCER RESEARCH LA English DT Article ID O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; ALKYLATING-AGENTS; ANTICANCER DRUGS; CELL-DEATH; APOPTOSIS; 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA; O-6-BENZYLGUANINE; DEPLETION; MEDULLOBLASTOMA; SENSITIVITY AB O-6-Methylguanine-DNA methyltransferase (MGMT), a constitutively expressed DNA repair protein, removes alkyl groups from the O-6-position of guanine in DNA, Tumor cells with high MGMT activity are resistant to nitrosoureas and other agents that form toxic O-6-alkyl adducts, O-6-Benzylguanine (BG) inactivates the MGMT protein and thereby enhances the sensitivity of tumor cells to alkylating drugs, However, the therapeutic potential of BG is limited by its poor solubility and its nonspecific inactivation of MGMT in normal tissues as well as in tumor tissues, Consequently, BG analogues are being developed to identify agents that have more favorable pharmacological characteristics. We evaluated O-6-benzyl-2'-deoxyguanosine (dBG), the 2'-deoxyribonucleoside analogue of BG, for its ability to inhibit MGMT and to potentiate 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in a MGMT-positive human brain tumor xenograft, Daoy. When given i.p. 1 h before BCNU (25 mg/m(2)) to animals bearing s.c. tumors, dBG (134 mg/m(2)) produced a growth delay of 24.7 days, compared to 21.6 days after treatment with an equimolar dose of BG (90 mg/m(2)) plus BCNU and -0.6 days after treatment with BCNU alone, The combination of dBG + BCNU also increased the survival of animals bearing intracranial tumors by 65%. By increasing the dose of dBG to 300 mg/m(2) (the maximum dose that could be delivered i.p. in a standard treatment volume), the growth delay of s.c. tumors increased from -0.1 days with BCNU alone to 39.3 days, dBG suppressed both tumor and liver MGMT activity to less than 1.5% of baseline, and dBG + BCNU induced extensive perivascular apoptosis, Because dBG is a 10-fold less potent MGMT inhibitor than BG in HT-29 cell extracts, these results illustrate the capacity of BG analogues to potentiate BCNU toxicity, despite less ira vitro activity than the parent compound, and emphasize the importance of in vivo evaluation of BG analogues. C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT CELLULAR & MOLEC PHYSIOL,HERSHEY,PA 17033. PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT PHARMACOL,HERSHEY,PA 17033. RP Schold, SC (reprint author), UNIV TEXAS,SW MED CTR,DEPT NEUROL,5323 HARRY HINES BLVD,DALLAS,TX 75235, USA. FU NCI NIH HHS [CA 57725] NR 28 TC 38 Z9 38 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1996 VL 56 IS 9 BP 2076 EP 2081 PG 6 WC Oncology SC Oncology GA UG756 UT WOS:A1996UG75600024 PM 8616853 ER PT J AU Szallasi, Z Du, L Levine, R Lewin, NE Nguyen, PN Williams, MD Pettit, GR Blumberg, PM AF Szallasi, Z Du, L Levine, R Lewin, NE Nguyen, PN Williams, MD Pettit, GR Blumberg, PM TI The bryostatins inhibit growth of B16/F10 melanoma cells in vitro through a protein kinase C-independent mechanism: Dissociation of activities using 26-epi-bryostatin 1 SO CANCER RESEARCH LA English DT Article ID PHASE-I; BINDING; DIFFERENTIATION; ASSAYS; LINES AB Bryostatin 1 is a potential cancer chemotherapeutic agent in Phase II clinical trials, with positive responses observed for malignant melanoma, among other tumors, The bryostatins are known to be potent ligands for protein kinase C (PKC), functioning as partial antagonists, In the present study, we explore the mechanism by which the bryostatins inhibit growth of B16/F10 mouse melanoma cells in vitro, Three experimental approaches suggest that the growth inhibition is independent of PKC, First, we characterized in detail the translocation and down-regulation of the PKC isozymes alpha, delta and epsilon in response to phorbol ester and bryostatin 1 in these cells, Although the dose-response curves obtained for the translocation-activation of PKC isozymes showed good correlation with the growth-enhancing activity of phorbol It-myristate 13-acetate, for no PKC isozyme was there a good correlation with the growth-inhibitory activity of bryostatin 1, Second, inhibition of PKC enzymatic activity by the specific PKC inhibitor bisindolyl-maleimide I did not block the inhibition of thymidine incorporation induced by bryostatin 1, Finally, 26-epi-bryostatin 1, a stereoisomer of the naturally occurring bryostatin 1 designed to have markedly reduced affinity for PKC, inhibited the growth of the B16/F10 melanoma cell lines with potency similar to that of bryostatin 1, We confirmed here that 26-epi-bryostatin 1 showed 60-fold reduced affinity for PKC and 30-60-fold reduced potency to translocate and downregulate PKC isozymes compared with hryostatin 1, We presume that the principal toxicity of bryostatin 1 reflects its interaction with PKC, and we would thus predict that epi-bryostatin 1 would be less toxic Indeed, we found at least 10-fold reduced toxicity of 26-epi-bryostatin 1 in C57BL/6 mice compared with bryostatin 1, We conclude that the growth inhibition of the bryostatins, at least in this system, does not result from interaction with PKC, As exemplified by 26-epi-bryostatin 1, this insight permits the design of analogues with comparable growth inhibition to bryostatin 1 but with reduced toxicity. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. ARIZONA STATE UNIV,DEPT CHEM,TEMPE,AZ 85287. ARIZONA STATE UNIV,CANC RES INST,TEMPE,AZ 85287. NR 26 TC 55 Z9 55 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1996 VL 56 IS 9 BP 2105 EP 2111 PG 7 WC Oncology SC Oncology GA UG756 UT WOS:A1996UG75600028 PM 8616857 ER PT J AU Greenblatt, MS Grollman, AP Harris, CC AF Greenblatt, MS Grollman, AP Harris, CC TI Deletions and insertions in the p53 tumor suppressor gene in human cancers: Confirmation of the DNA polymerase slippage misalignment model SO CANCER RESEARCH LA English DT Article ID SHORT SEQUENCE HOMOLOGIES; MUTATION HOT-SPOT; COLORECTAL-CANCER; INDUCED FRAMESHIFT; MUTAGENESIS; ADDUCT; CELLS; INSTABILITY; MECHANISMS; INVITRO AB We analyzed all published deletions and insertions in the p53 gene to assess the relevance of mutagenesis models, Almost all deletions and insertions can be explained by one or more of the following DNA sequence features: monotonic base runs, adjacent or nonadjacent repeats of short tandem sequences, palindromes, and runs of purines or pyrimidines (homocopolymer runs), Increased length of monotonic runs correlates positively with increased frequency of events, Complex frameshift mutations can be explained by the formation of quasi-palindromes, with mismatch excision and replication using one strand of the palindrome as a template, Deletions and insertions in the p53 tumor suppressor gene may reflect both spontaneous and carcinogen-induced mutagenesis. C1 NCI,HUMAN CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. SUNY STONY BROOK,DEPT PHARMACOL SCI,STONY BROOK,NY 11794. NR 60 TC 102 Z9 104 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1996 VL 56 IS 9 BP 2130 EP 2136 PG 7 WC Oncology SC Oncology GA UG756 UT WOS:A1996UG75600032 PM 8616861 ER PT J AU Sargent, LM Sanderson, ND Thorgeirsson, SS AF Sargent, LM Sanderson, ND Thorgeirsson, SS TI Ploidy and karyotypic alterations associated with early events in the development of hepatocarcinogenesis in transgenic mice harboring c-myc and transforming growth factor alpha transgenes SO CANCER RESEARCH LA English DT Article ID PRIMARY HEPATOCELLULAR-CARCINOMA; FRAGILE SITES; LIVER NEOPLASIA; FREQUENT LOSS; WILMS-TUMOR; MOUSE; HETEROZYGOSITY; CANCER; PROGRESSION; RAT AB The cooperation of the c-myc oncogene with the growth factor transforming growth factor (TGF)-alpha in development of liver tumors in transgenic mice has been demonstrated previously. In this study, we analyzed the ploidy and karyotype of c-myc, TGF-alpha, parental control, and the double transgenic c-myc/TGF-alpha hepatocytes at 3 weeks of age when the liver is histologically normal and at 10 weeks when the c-myc/TGF-alpha liver is dysplastic and contains basophilic foci, Eighty % of the 10-week hepatocytes were aneuploid, and 32% had chromosomal breakage, Statistically significant breakage was observed in six different chromosomes. Breakage at band A5 and at the border of bands C4/5 of chromosome 1 was observed, Fragile sites on chromosome 4 were most frequent in the middle of the chromosome at bands C2 and C6. Chromosome 6 was fragile at band F2, The region of chromosome 7 at bands B5 and D3 was frequently broken and involved in translocations. Chromosome 12 was broken at bands D1 and D3, The breakage sites on chromosomes 1, 4, 7, and 12 correspond to sites of tumor susceptibility genes in the mouse, Although there was no consistent change in copy number, recurrent translocations between chromosomes 1, 4, 7, 12, and 19 were also observed, These studies demonstrate that the development of dysplasia and basophilic foci in the liver is correlated with aneuploidy and chromosome breakage, The specific fragile sites indicate genetic regions that are altered during early stages of hepatocarcinogenesis. Due to the conservation of genetic linkage groups between mice and humans, the identification of genetic alterations in the mouse during hepatocarcinogenesis may provide critical information about tumor susceptibility genes that are important in the early development of human hepatocellular carcinoma. C1 NCI,DIV BASIC SCI,LAB EXPTL CARCINOGENESIS,BETHESDA,MD 20892. NR 58 TC 47 Z9 47 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1996 VL 56 IS 9 BP 2137 EP 2142 PG 6 WC Oncology SC Oncology GA UG756 UT WOS:A1996UG75600033 PM 8616862 ER PT J AU Palmantier, R Roberts, JD Glasgow, WC Eling, TE Olden, K AF Palmantier, R Roberts, JD Glasgow, WC Eling, TE Olden, K TI Regulation of the adhesion of a human breast carcinoma cell line to type IV collagen and vitronectin: Roles for lipoxygenase and protein kinase C SO CANCER RESEARCH LA English DT Article ID MAMMARY ADENOCARCINOMA CELLS; ARACHIDONIC-ACID; CANCER-CELLS; LUNG; EXPRESSION; ACTIVATION; METASTASIS; METABOLISM; RECEPTOR; GROWTH AB We have investigated the regulation of adhesion of metastatic human breast carcinoma cells to various protein substrates in the presence or absence of the protein kinase C (PKC) activator, 12-tetradecanoyl phorbol 13-acetate (TPA) of calcium ionophore A23187 (A23187). Both TPA and A23187 dramatically enhanced MDA-MB-435 cell adhesion to type IV collagen (collagen IV), vitronectin, and, to some extent, fibronectin and laminin. Adhesion to BSA and polylysine were not affected. TPA and A23187 induced substantial dose-dependent effects that were apparent after 30- and 60-min incubations, respectively, whereas a phorbol ester, which does not activate PKC, had no effect. A23187, but not TPA, induced a release of arachidonic acid (AA) from MDA-MB-435 cells. Nordihydroguaiaretic acid, a lipoxygenase inhibitor, prevented A23187 and exogenous AA, but not TPA, from stimulating cell adhesion to collagen IV. In contrast, the increase in adhesion to vitronectin induced by A23187 and AA was, at best, only partially inhibited by nordihydroguaiaretic acid treatment. Calphostin C, a PKC inhibitor, blocked the stimulation of adhesion by A23187, exogenous AA, and TPA to both collagen IV and vitronectin. Together, these results suggest that calcium mobilization activates the release of AA and its metabolism through a lipoxygenase pathway leading to a rapid increase of MDA-MB-OS cell adhesion to collagen IV, whereas other mechanisms regulate adhesion to vitronectin. Finally, PKC activation, occurring downstream from calcium mobilization or the AA effects, is a key event involved in the regulation of adhesion to both proteins. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. RP Palmantier, R (reprint author), NIEHS,MOLEC CARCINOGENESIS LAB,MAIL DROP C2-14,RES TRIANGLE PK,NC 27709, USA. NR 45 TC 37 Z9 37 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1996 VL 56 IS 9 BP 2206 EP 2212 PG 7 WC Oncology SC Oncology GA UG756 UT WOS:A1996UG75600044 PM 8616873 ER PT J AU Hu, ZY Evarts, RP Fujio, K Omori, N Omori, M Marsden, ER Thorgeirsson, SS AF Hu, ZY Evarts, RP Fujio, K Omori, N Omori, M Marsden, ER Thorgeirsson, SS TI Expression of transforming growth factor alpha epidermal growth factor receptor, hepatocyte growth factor c-met and acidic fibroblast growth factor fibroblast growth factor receptors during hepatocarcinogenesis SO CARCINOGENESIS LA English DT Article ID LIVER EPITHELIAL-CELLS; FAT-STORING CELLS; RAT-LIVER; HEPATIC DIFFERENTIATION; HEPATOCELLULAR-CARCINOMA; REGENERATING LIVER; SCATTER FACTOR; OVAL CELLS; TGF-ALPHA; AUTOCRINE AB It is widely believed that abnormal production of polypeptide growth factors, together with other molecular alterations, play an important role in neoplastic development. Transforming growth factor alpha (TGF alpha), hepatocyte growth factor (HGF) and acidic fibroblast growth factor (aFGF) are the three major growth factors that contribute to liver regeneration occurring via both hepatocyte replication and oval cell proliferation. It is not clear, however, whether and to what extent these growth factors are also involved in hepatocarcinogenesis. In the present study, the gene expression of TGF alpha, HGF and aFGF and their corresponding receptors was examined by Northern blotting and in situ hybridization during hepatocarcinogenesis induced by the Solt-Farber protocol. All three growth factor/receptor systems, TGF alpha/epidermal growth factor receptor (EGFR), HGF/c-met and aFGF/FGF receptors (flg and bek) were significantly elevated at early time points when oval cells were proliferating. Their respective expression decreased after 1 month and remained at a low level until the development of liver tumors. In all hepatocellular carcinomas (HCC) examined, the transcripts of TGF alpha and aFGF were highly expressed, while those of HGF were low. With regard to the receptor expression in the tumors, EGFR was present at varying levels, c-met was expressed at higher levels and flg increased significantly, whereas bek remained at low levels. These data suggest that TGF alpha and aFGF are the major growth factors involved in the progression of HCC, and that the signal of aFGF is mainly transduced by the receptor flg in HCC. Furthermore, HCC cells were phenotypically very similar to oval cells with regard to the gene expression of growth factor/receptor systems. These results, along with the finding that all the HCC cells are positive for the oval cell antigen OV6, and that cytokeratin 19 is heavily expressed in both tumor and oval cells, strongly suggest that at least some of the HCC induced by the Solt-Farber protocol may be derived from oval cells. RP Hu, ZY (reprint author), NCI,EXPTL CARCINOGENESIS LAB,NIH,37 CONVENT DR,BETHESDA,MD 20892, USA. NR 58 TC 62 Z9 63 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1996 VL 17 IS 5 BP 931 EP 938 DI 10.1093/carcin/17.5.931 PG 8 WC Oncology SC Oncology GA UL750 UT WOS:A1996UL75000006 PM 8640940 ER PT J AU Soini, Y Chia, SC Bennett, WP Groopman, JD Wang, JS DeBenedetti, VMG Cawley, H Welsh, JA Hansen, C Bergasa, NV Jones, EA DiBisceglie, AM Trivers, GE Sandoval, CA Calderon, IE Espinosa, LEM Harris, CC AF Soini, Y Chia, SC Bennett, WP Groopman, JD Wang, JS DeBenedetti, VMG Cawley, H Welsh, JA Hansen, C Bergasa, NV Jones, EA DiBisceglie, AM Trivers, GE Sandoval, CA Calderon, IE Espinosa, LEM Harris, CC TI An aflatoxin-associated mutational hotspot at codon 249 in the p53 tumor suppressor gene occurs in hepatocellular carcinomas from Mexico SO CARCINOGENESIS LA English DT Article ID HEPATITIS-B VIRUS; ALBUMIN; EXPOSURE; BIOMARKERS; ANTIGEN; INVITRO; ADDUCTS; LIVER AB The p53 tumor suppressor gene is commonly mutated in human hepatocellular carcinoma (HCC), The most frequent mutation in HCC in populations exposed to a high dietary intake of aflatoxin B1 (AFB1) is an AGG(arg)-->AGT(ser) missense mutation in codon 249 of the p53 gene, We analyzed HCCs from Monterrey, Mexico, for the codon 249(ser) hotspot mutation, We also analyzed the serum AFB1-albumin adduct levels of the donors and family members to measure the current AFB1 exposure in this population, Moreover, the presence of hepatitis B and/or C viral infection (HBV or HCV) was analyzed serologically in the patients. Tumor cells were microdissected from tissue sections and exon 7 p53 sequences were amplified by polymerase chain reaction from genomic DNA and sequenced directly, The serological tests for anti-p53 antibodies, HBV or HCV were done by ELISA, Immunohistochemical analysis of p53 protein was done using a polyclonal rabbit antiserum (CM-1). Eight of 21 cases were positive by p53 immunohistochemistry. Of the 16 cases sequenced for exon 7 of p53 three codon 249 AGG(arg)-->AGT(ser) mutations were found, Serum antibodies recognizing p53 protein were found in one of 18 patients, Positive serology for HBV and/or HCV was found in 12 of 20 cases, The serum AFB1-albumin adduct levels in this population ranged from 0.54 to 4.64 pmol aflatoxin/mg albumin, These results indicate that dietary AFB1 and hepatitis viruses are etiological agents in the molecular pathogenesis of HCC in this geographic region of Mexico. C1 NCI,HUMAN CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. TAO PAYOH HOSP,SINGAPORE 1129,SINGAPORE. UNIV OULU,DEPT PATHOL,OULU,FINLAND. JOHNS HOPKINS UNIV,BALTIMORE,MD 21205. DR JOSE E GONZALEZ UNIV HOSP,DEPT GASTROENTEROL,LIVER UNIT,MONTERREY,NUEVO LEON,MEXICO. FU NIEHS NIH HHS [P01-ES06052] NR 52 TC 74 Z9 80 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1996 VL 17 IS 5 BP 1007 EP 1012 DI 10.1093/carcin/17.5.1007 PG 6 WC Oncology SC Oncology GA UL750 UT WOS:A1996UL75000016 PM 8640905 ER PT J AU Sargent, LM Dragan, YP Sattler, C Bahnub, N Sattler, G Martin, P Cisneros, A Mann, J Thorgeirsson, S Jordan, VC Pitot, HC AF Sargent, LM Dragan, YP Sattler, C Bahnub, N Sattler, G Martin, P Cisneros, A Mann, J Thorgeirsson, S Jordan, VC Pitot, HC TI Induction of hepatic aneuploidy in vivo by tamoxifen, toremifene and idoxifene in female Sprague-Dawley rats SO CARCINOGENESIS LA English DT Article ID CELL-CYCLE PROGRESSION; BREAST-CANCER; DNA-SYNTHESIS; CALMODULIN; LIVER; ANTIESTROGENS; HEPATOCYTES; METABOLITES; RECEPTOR; ANALOGS AB Since tamoxifen is efficacious for the prevention of second primary breast neoplasms in humans and has a low reported incidence of acute side effects, several structurally related compounds have been developed for the treatment of breast cancer including toremifene and idoxifene, We have compared the karyotypic alterations that occur after a single per os administration of 35 mg/kg of tamoxifen, toremifene or idoxifene to female Sprague-Dawley rats, One day following treatment, the rats were sacrificed and the hepatocytes isolated and cultured, After 47 h in culture, colcemid was added for 3 h prior to harvest of the hepatocytes for karyotypic evaluation, At least 100 metaphase spreads mere examined for each of five rats per treatment, Toremifene resulted in aneuploidy in 50+/-7% of the cells examined and idoxifene induced a 57+/-4% aneuploidy compared with the 85+/-7% level induced by tamoxifen, Since the level of aneuploidy in solvent-treated rats was 3+/-3%, the induction of aneuploidy in at least 50% of the cells from rats treated with tamoxifen, toremifene or idoxifene was highly significant, Analysis of electron micrographs of cultures treated with these antiestrogens demonstrated a range of phenotypes including multipolar spindles in toremifene-treated rats and condensed chromosomes in the presence of an intact nuclear envelope in occasional idoxifene-treated rat hepatocytes. The exclusion of chromosomes from the spindle apparatus and the lagging of some chromosomes on the metaphase plate correlate with the high rate of induction of aneuploidy in the rat liver as determined by karyotypic analysis of hepatocytes from rats treated with these triphenylethylenes. C1 UNIV READING,DEPT CHEM,READING RG6 2AD,BERKS,ENGLAND. NORTHWESTERN UNIV,ROBERT LURIE CANC CTR,CHICAGO,IL 60611. UNIV WISCONSIN,SCH MED,MCARDLE LAB CANC RES,MADISON,WI 53706. RP Sargent, LM (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. RI Jordan, V. Craig/H-4491-2011 NR 52 TC 30 Z9 31 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1996 VL 17 IS 5 BP 1051 EP 1056 DI 10.1093/carcin/17.5.1051 PG 6 WC Oncology SC Oncology GA UL750 UT WOS:A1996UL75000023 PM 8640912 ER PT J AU Grant, S Freemerman, AJ Birrer, MJ Martin, HA Turner, AJ Szabo, E Chelliah, J Jarvis, WD AF Grant, S Freemerman, AJ Birrer, MJ Martin, HA Turner, AJ Szabo, E Chelliah, J Jarvis, WD TI Effect of 1-beta-D-arabinofuranosylcytosine on apoptosis and differentiation in human monocytic leukemia cells (U937) expressing a c-jun dominant-negative mutant protein (TAM67) SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; HL-60 CELLS; MACROPHAGE DIFFERENTIATION; POTENTIAL INVOLVEMENT; TRANSCRIPTION FACTOR; GENE-EXPRESSION; CYTO-TOXICITY; MYC GENE; FOS JUN; DNA AB The proto-oncogene c-jun encodes a component of the AP-1 transcription-activating complex and has been implicated in the regulation of diverse cellular processes, including cell proliferation, differentiation, transformation, and most recently, apoptosis. We have used a U937 monocytic leukemia cell line stably expressing a c-jun dominant-negative, transactivation-domain deletion mutant (TAM67) to assess the role of c-jun in apoptotic events induced by exposure to the antimetabolite 1-beta-D-arabinofuranosylcytosine (ara-C). Mutant cells produce a truncated M(r) 29,000 protein that interferes with the function of normal c-Jun (and c-Fos) proteins through a quenching mechanism. Parental U937, cells expressing TAM67, and cells carrying only the empty vector (pMM) were exposed to ara-C for 6 h, and apoptosis was monitored by cell morphology as well as qualitative and quantitative assays of DNA damage. No differences in apoptosis could be detected between the three cell lines at any of the ara-C concentrations evaluated. In addition, ara-C concentrations greater than or equal to 1.0 x 10(-6) M were equally inhibitory to the clonogenic growth of U937 and TAM67-expressing cells. In contrast, lower concentrations of ara-C (i.e., less than or equal to 5.0 x 10(-7) M) were significantly less inhibitory to mutant U937 cell colony formation than to their parental counterparts. The reduced sensitivity of TAM67-expressing cells to low concentrations of ara-C could not be attributed to biochemical or cytokinetic factors, since the two cell lines were indistinguishable with respect to 1-beta-D-arabinofuranosylcytosine 5'-triphosphate (ara-CTP) formation, ara-CTP:dCTP ratios, and S-phase fraction. However, a significantly lower percentage of TAM67-expressing cells exposed to submicromolar concentrations of ara-C exhibited features associated with a differentiated monocytoid phenotype (i.e., increased plastic adherence and CD11b expression) compared to their parental counterparts. Lower concentrations of ara-C were also significantly less effective in decreasing the percentage of S-phase cells and in down-regulating c-myc mRNA levels in the mutant line, events associated with induction of leukemic cell differentiation. Finally, ara-C-induced up-regulation of c-jun message and protein was markedly attenuated in TAM67-expressing cells, findings consistent with a c-jun dominant-negative model. Collectively, these findings suggest that dysregulation of c-jun in U937 cells antagonizes low-dose ara-C-mediated cellular maturation but does not prevent higher concentrations of this agent from triggering apoptosis. They also raise the possibility that separate aspects of the antiproliferative actions of ara-C may be differentially regulated by c-jun. C1 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PHARMACOL & TOXICOL,RICHMOND,VA 23298. NCI,BIOMARKERS & PREVENT BRANCH,BETHESDA,MD 20892. RP Grant, S (reprint author), VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT MED,DIV HEMATOL ONCOL,MCV STN BOX 230,RICHMOND,VA 23298, USA. FU NCI NIH HHS [CA 09564, R01 CA 63753, R03 CA 66990] NR 64 TC 41 Z9 41 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD MAY PY 1996 VL 7 IS 5 BP 603 EP 613 PG 11 WC Cell Biology SC Cell Biology GA UJ264 UT WOS:A1996UJ26400006 PM 8732670 ER PT J AU Tennenbaum, T Li, LW Belanger, AJ De Luca, LM Yuspa, SH AF Tennenbaum, T Li, LW Belanger, AJ De Luca, LM Yuspa, SH TI Selective changes in laminin adhesion and alpha(6)beta(4) integrin regulation are associated with the initial steps in keratinocyte maturation SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID EXTRACELLULAR CALCIUM CONCENTRATIONS; SQUAMOUS-CELL CARCINOMAS; TERMINAL DIFFERENTIATION; CYTOPLASMIC DOMAIN; HUMAN-SKIN; FLUOROMETRIC ASSAY; EPITHELIAL-CELLS; EPIDERMAL-CELLS; EXPRESSION; GROWTH AB In skin, the distribution of integrins is compartmentalized. Whereas the alpha(6) beta(4) integrin complex is polarized to the basal portion of proliferating cells in the basal layer juxtaposed to the basement membrane, alpha(3) beta(1) integrin receptors are localized on the cell surface surrounding basal and suprabasal cells, suggesting beta(1) integrins mediate both cell-matrix and cell-cell interactions. As initiation of maturation in skin is associated with the detachment of cells from the basement membrane, the early loss of alpha(6) beta(4) but not alpha(3) beta(1) integrin expression could be a determining factor in the transition from the proliferating to a differentiating keratinocyte. We have studied the regulation of adhesion potential and integrin expression during differentiation of mouse basal keratinocytes cultured in 0.05 mM Ca2+ medium and induced to differentiate in 0.12 mM Ca2+ medium. Within 12-24 h after elevation of Ca2+, a selective loss of the alpha(6) beta(4) integrin complex is associated with the induction of the spinous cell marker keratin 1. This early differentiation phenotype coincides with loss of cell attachment mediated by alpha(6) beta(4) to laminins 1 and 5 but not to fibronectin or collagen IV. Selective loss of attachment to laminin is also detected in spinous cells isolated from newborn epidermis in vivo. The loss of alpha(6) beta(4) protein expression is a consequence of transcriptional and posttranslational events, including reduction in mRNA transcripts, reduced synthesis of the alpha(6) protein, and enhanced processing of the alpha(6) and beta(4), chains as determined by Western blots and pulse-chase experiments in metabolically labeled keratinocytes. Selective processing of the beta(4) intracellular domain is detected before loss of beta(4) from the cell surface in basal keratinocytes, and this process is accelerated during differentiation. Whereas early keratinocyte maturation is linked to the selective loss of the alpha(6) beta(4) complex, loss of both beta(1) and beta(4) integrin mRNA and protein occurs as cells proceed to later stages in the differentiation program as induced by 0.5 mM Ca2+ or suspension culture. These conditions are characterized by accelerated expression of transglutaminase; reduced keratin 1 protein; loss of adhesion to fibronectin, laminin 1, laminin 5, and collagen IV; and rapid cell death. Contributing to the down-regulation of beta(1) integrins during terminal differentiation is a selective sensitivity of alpha(3) beta(1) but not alpha(6) beta(4) to down-regulation by transforming growth factors beta(1) and beta(2), factors that are also expressed differentially in normal skin. This study indicates that down-regulation of the alpha(6) beta(4) but not beta(1) integrins occurs during the initial steps of keratinocyte differentiation and is associated with detachment from the laminin matrix. Such changes could contribute an important signal to initiate the process of terminal keratinocyte differentiation. C1 NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, NIH, BETHESDA, MD 20892 USA. NR 76 TC 48 Z9 49 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD MAY PY 1996 VL 7 IS 5 BP 615 EP 628 PG 14 WC Cell Biology SC Cell Biology GA UJ264 UT WOS:A1996UJ26400007 PM 8732671 ER PT J AU Feng, P Ge, L Akyhani, N Liau, G AF Feng, P Ge, L Akyhani, N Liau, G TI Sodium butyrate is a potent modulator of smooth muscle cell proliferation and gene expression SO CELL PROLIFERATION LA English DT Article ID GROWTH-FACTOR; CYCLIC-AMP; MESSENGER-RNA; FATTY-ACID; DIFFERENTIATION; INDUCTION; ARREST; ATHEROSCLEROSIS; THROMBOSPONDIN; INHIBITION AB Sodium butyrate is a small, naturally occurring molecule with demonstrated activity on cell growth and differentiation. However, its effect on smooth muscle cells had not been examined, We have found that sodium butyrate and its more stable in vivo analogue tributyrin are potent DNA synthesis and cell proliferation inhibitors, The inhibitory activity of sodium butyrate was not mediated by an elevation of endogenous cAMP levels, a known pathway involved in SMC growth-arrest and maintenance of the contractile phenotype, Consistent with the concept that its activity is mediated by a cAMP-independent pathway, butyrate was able to augment the maximum DNA synthesis inhibitory effect of various agents that elevated intracellular cAMP levels, Additionally, butyrate present for just the initial 8 h or present as late as 16 h after serum addition was able to inhibit DNA synthesis, By contrast, the cAMP analogue, 8Br-cAMP had to be present throughout the entire G(0), to S phase of the cell cycle to effectively inhibit DNA synthesis, These results indicated that sodium butyrate inhibited SMC growth through a cAMP-independent mechanism. We also found that sodium butyrate was unable to abrogate the expression of the serum-inducible genes c-fos, c-myc, Ki-Ras and PS4, but was able to directly stimulate the expression of PS4 and thrombospondin, These results indicate that a number of important early G(1) events initiated by serum growth factors are unaltered by sodium butyrate and that this compound is able to directly stimulate the expression of certain genes normally associated with SMC proliferation. C1 AMER RED CROSS,JEROME H HOLLAND LAB,DEPT MOL BIOL,ROCKVILLE,MD 20855. NIH,BETHESDA,MD 20892. HUMAN GENOME SCI,ROCKVILLE,MD 20850. FU NHLBI NIH HHS [HL 37510] NR 41 TC 12 Z9 13 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0960-7722 J9 CELL PROLIFERAT JI Cell Prolif. PD MAY PY 1996 VL 29 IS 5 BP 231 EP 241 DI 10.1046/j.1365-2184.1996.00998.x PG 11 WC Cell Biology SC Cell Biology GA VD506 UT WOS:A1996VD50600002 PM 8782486 ER PT J AU McVicar, DW Blake, TB Burns, CM Conlon, KC Ortaldo, JR OShea, JJ AF McVicar, DW Blake, TB Burns, CM Conlon, KC Ortaldo, JR OShea, JJ TI Differential basal protein tyrosine phosphorylation in natural killer (NK) and T cells: A biochemical correlate of lymphoid functional activity SO CELLULAR IMMUNOLOGY LA English DT Article ID INTERFERON-GAMMA PRODUCTION; SIGNAL TRANSDUCTION; IGG FC; ACTIVATION; KINASE; CYTOTOXICITY; LYMPHOCYTES; P56(LCK); COMPLEX; TCR AB Despite the similarities between natural killer (NK) and T cells, these lymphocytes have dramatically different functional phenotypes. To identify potential biochemical parameters that correlate with the ''primed'' NK phenotype, we have investigated protein tyrosine phosphorylation in NK and T cells. Examination of tyrosyl phosphorylation in NK cells showed that they have higher levels of phosphorylation than resting T cells. Consistent with this, the concentrations of the tyrosine kinase inhibitor, herbimycin A, required to inhibit FcR-mediated Ca2+ flux in NK cells were much higher than those required for inhibition of T cell receptor-mediated Ca2+ mobilization. Differences in phosphorylation were not due to purification artifact or explained by differential expression of the prominent lymphocyte src-family kinase, p56(lck) or the protein tyrosine phosphatase CD45. Thus, we have identified high basal tyrosyl phosphorylation as a striking biochemical feature of NR cells that correlates with the unique functions of this subset. (C) 1996 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,LAB IMMUNE CELL BIOL,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RP McVicar, DW (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,EXPTL IMMUNOL LAB,FREDERICK,MD 21702, USA. RI McVicar, Daniel/G-1970-2015 NR 40 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD MAY 1 PY 1996 VL 169 IS 2 BP 302 EP 308 DI 10.1006/cimm.1996.0122 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA UJ456 UT WOS:A1996UJ45600017 PM 8620559 ER PT J AU Gawne, TJ Kjaer, TW Hertz, JA Richmond, BJ AF Gawne, TJ Kjaer, TW Hertz, JA Richmond, BJ TI Adjacent visual cortical complex cells share about 20% of their stimulus-related information SO CEREBRAL CORTEX LA English DT Article ID TWO-DIMENSIONAL PATTERNS; INFERIOR TEMPORAL CORTEX; SINGLE UNITS; MONKEY; CAT AB The responses of adjacent neurons in inferior temporal (IT) cortex carry signals that are to a large degree independent (Gawne and Richmond, 1993), Adjacent primary visual cortical neurons have similar orientation tuning (Hubel and Wiesel, 1962, 1968), suggesting that their responses might be more redundant than those in IT. We recorded the responses of 26 pairs of adjacent complex cells in the primary visual cortex of two awake monkeys while using both a set of 16 bar-like stimuli, and a more complex set of 128 two-dimensional patterns. Linear regression showed that 40% of the signal variance of one neuron was related to that of the other when the responses to the bar-like stimuli were considered. However, when the responses to the two-dimensional stimuli were included in the analysis, only 19% of the signal variance of one neuron was related to that of the adjacent one, almost exactly the same results as found in IT, An information theoretic analysis gave similar results, We hypothesize that this trend toward independence of information processing by adjacent cortical neurons is a general organizational strategy used to maximize the amount of information carried in local groups. C1 NORDITA,DK-2100 COPENHAGEN,DENMARK. RP Gawne, TJ (reprint author), NIMH,NEUROPSYCHOL LAB,49 CONVENT DR,MSC 4415,BLDG 49,ROOM 1B80,BETHESDA,MD 20892, USA. NR 24 TC 84 Z9 84 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD MAY-JUN PY 1996 VL 6 IS 3 BP 482 EP 489 DI 10.1093/cercor/6.3.482 PG 8 WC Neurosciences SC Neurosciences & Neurology GA UL409 UT WOS:A1996UL40900014 PM 8670673 ER PT J AU Okhuysen, RS Bristow, F Burkhead, S Kolobow, T Lally, KP AF Okhuysen, RS Bristow, F Burkhead, S Kolobow, T Lally, KP TI Evaluation of a new thin-walled endotracheal tube for use in children SO CHEST LA English DT Article DE airway resistance; airway stenosis; endotracheal tubes; mechanical ventilation; work of breathing ID VENTILATION; PRESSURE; SUPPORT; WORK AB Conventional endotracheal tabes have high intrinsic resistive properties due to their high outer-to-inner diameter ratio, This has significant disadvantages in the treatment of the small neonatal or pediatric patient as work of breathing increases with decreasing internal radius, Diagnostic and therapeutic procedures, including suctioning, may be very difficult in patients with small endotracheal tubes, We therefore measured airway resistance and pressure differential during simulated mechanical ventilation using proximal and distal endotracheal tube Row transducers. Conventional and new, ultrathin-walled endotracheal tubes reinforced with flat stainless steel or a novel, crush-proof nickel-titanium alloy were compared using fixed ventilator settings, Ventilation through the ultrathin-walled tubes resulted in a significantly reduced airway resistance (p less than or equal to 0.01). These new ultrathin-walled endotracheal tubes showed flow characteristics typical of much larger conventional endotracheal tubes: the 3.2-mm internal diameter had an airway resistance (Raw) of 36, while a standard 2.5-mm internal diameter endotracheal tube had a Raw of 146, Both endotracheal tubes have identical external diameters of 3.6 mm, We conclude that ultrathin-walled endotracheal tubes could have a significant role in the treatment of the ventilated child by facilitating interactive ventilation and maintenance of airway patency and may make procedures such as fiberoptic endoscopy and intrapulmonary ventilation using reverse-thrust catheters possible in the small child. C1 UNIV TEXAS,HLTH SCI CTR,DIV SURG,HOUSTON,TX. UNIV TEXAS,HLTH SCI CTR,RESP CARE DIV,HOUSTON,TX. HERMANN CHILDRENS HOSP,HOUSTON,TX. NIH,CELL BIOL LAB,BETHESDA,MD. RP Okhuysen, RS (reprint author), UNIV TEXAS,HLTH SCI CTR,DIV PEDIAT CRIT CARE,HOUSTON,TX, USA. NR 14 TC 1 Z9 1 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD MAY PY 1996 VL 109 IS 5 BP 1335 EP 1338 DI 10.1378/chest.109.5.1335 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA UK625 UT WOS:A1996UK62500037 PM 8625687 ER PT J AU Lenfant, C AF Lenfant, C TI Task force on research in epidemiology and prevention of cardiovascular diseases - A revisit SO CIRCULATION LA English DT News Item RP Lenfant, C (reprint author), NHLBI,BLDG 31,ROOM 5A52,31 CTR DR,MSC 2486,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 1 PY 1996 VL 93 IS 9 BP 1605 EP 1607 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA UG813 UT WOS:A1996UG81300003 PM 8653860 ER PT J AU Eisenhofer, G Friberg, P Rundqvist, B Quyyumi, AA Lambert, G Kaye, DM Kopin, IJ Goldstein, DS Esler, MD AF Eisenhofer, G Friberg, P Rundqvist, B Quyyumi, AA Lambert, G Kaye, DM Kopin, IJ Goldstein, DS Esler, MD TI Cardiac sympathetic nerve function in congestive heart failure SO CIRCULATION LA English DT Article DE norepinephrine; heart failure; nervous system, autonomic; radioisotopes ID NOREPINEPHRINE KINETICS; NEURONAL UPTAKE; PLASMA; DIHYDROXYPHENYLALANINE; CATECHOLAMINES; DEPENDENCE; SPILLOVER; DEPLETION; TRANSPORT; HAMSTER AB Background Increased availability of norepinephrine (NE) for activation of cardiac adrenoceptors (increased cardiac adrenergic drive) and depletion of myocardial NE stores may contribute to the pathophysiology and progression of congestive heart failure. This study used a comprehensive neurochemical approach to examine the mechanisms responsible for these abnormalities. Methods and Results Subjects with and without congestive heart failure received intravenous infusions of [H-3]NE. Cardiac spillover, reuptake, vesicular-axoplasmic exchange, and tissue Stores of NE were assessed from arterial and coronary venous plasma concentrations of endogenous and [H-3]-labeled NE and dihydroxyphenylglycol. Tyrosine hydroxylase activity was assessed from plasma dopa, and NE turnover was assessed from measurements of NE metabolites. NE release and reuptake were both increased in the failing heart; however, the efficiency of NE reuptake was reduced such that cardiac spillover of NE was increased disproportionately more than neuronal release of NE. Cardiac NE stores were 47% lower and the rate of vesicular leakage of NE was 42% lower in the failing than in the normal heart. Cardiac spillover of dopa and NE turnover were increased similarly in congestive heart failure. Conclusions Increased neuronal release of NE and decreased efficiency of NE reuptake both contribute to increased cardiac adrenergic drive hi congestive heart failure. Decreased vesicular leakage of NE, secondary to decreased myocardial stores of NE, limits the increase in cardiac NE turnover in CHF. Decreased NE store size in the failing heart appears to result not from insufficient tyrosine hydroxylation but from chronically increased NE turnover and reduced efficiency of NE reuptake and storage. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. GOTHENBURG UNIV,DEPT CARDIOL,GOTHENBURG,SWEDEN. GOTHENBURG UNIV,DEPT CLIN PHYSIOL,GOTHENBURG,SWEDEN. BAKER MED RES INST,PRAHRAN,VIC 3181,AUSTRALIA. RP Eisenhofer, G (reprint author), NHLBI,CLIN NEUROSCI BRANCH,NIH,BLDG 10,ROOM 5N-214,10 CTR DR MSC 1424,BETHESDA,MD 20892, USA. RI Lambert, Gavin/E-7384-2010 OI Lambert, Gavin/0000-0003-0315-645X NR 40 TC 300 Z9 310 U1 2 U2 16 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 1 PY 1996 VL 93 IS 9 BP 1667 EP 1676 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA UG813 UT WOS:A1996UG81300015 PM 8653872 ER PT J AU Sharp, DS Curb, JD Schatz, IJ Meiselman, HJ Fisher, TC Burchfiel, CM Rodriguez, BL Yano, K AF Sharp, DS Curb, JD Schatz, IJ Meiselman, HJ Fisher, TC Burchfiel, CM Rodriguez, BL Yano, K TI Mean red cell volume as a correlate of blood pressure SO CIRCULATION LA English DT Article DE blood pressure; blood viscosity; erythrocytes; vascular resistance ID CARDIOVASCULAR RISK-FACTORS; ESSENTIAL-HYPERTENSION; POPULATION; VISCOSITY; ADULTS; HEMATOCRIT; NUTRITION; MEN AB Background Clinical studies suggest that hypertensives have lower mean corpuscular volume (MCVs) than do normotensives. Epidemiological studies show no relation or higher MCVs. In the present study of elderly men (71 to 93 years of age) of the Honolulu Heart Program, elements of both findings are confirmed. Methods and Results Three groups are identified: (1) those receiving no hypertension treatment, (2) those receiving treatment with any diuretic, and (3) those receiving treatment with nondiuretics only. MCV is lower in group 3 than in group 1 (-0.85 fL, p<.001) but the same in groups 1 and 2. Within groups 1 and 3, inverse relations of -0.22 and -0.09 mm Hg/fL (P<.05) are noted for systolic (SEP) and diastolic (DBP) blood pressures. No relations are observed in group 2. MCV and red blood cell count (RBC) are inversely correlated (r=-.45). In group 2, adjustment for RBC unmasks a direct relation between MCV and SEP (0.5 mm Hg/fL, P=.02) and DBP (0.3 mm Hg/fL, P=.02). In groups 1 and 3, relations between SEP and MCV are lost after adjustment for RBC (0.005 mm Hg/fL). For DBP, adding RBC plus an MCVxRBC interaction is significant (P<.001). DBP is 5 mm Hg greater in the highest RBC quartile than in the lowest. A +3 mm Hg difference between extreme MCV quartiles is noted only at high RBC levels. Conclusions The relation between blood pressure and red cell measures is probably mediated by whole blood viscosity. Hematocrit is a determinant of whole blood viscosity. Viscosity affects peripheral resistance to blood flow, and peripheral resistance affects DBP. At high RBC levels, MCV may be ''downregulated.'' This may lower whole blood viscosity and partially reduce DBP without compromising flow. C1 NHLBI,HONOLULU EPIDEMIOL RES UNIT,HONOLULU,HI. NHLBI,FIELD STUDIES & CLIN EPIDEMIOL SCI RES GRP,EPIDEMIOL & BIOMETRY PROGRAM,HONOLULU,HI. KUAKINI MED CTR,HONOLULU HEART PROGRAM,HONOLULU,HI. UNIV HAWAII MANOA,JOHN A BURNS SCH MED,DEPT MED,HONOLULU,HI 96822. UNIV SO CALIF,SCH MED,DEPT PHYSIOL & BIOPHYS,LOS ANGELES,CA 90033. FU NHLBI NIH HHS [HL-48484, N01-HC-05102, HL-15722] NR 33 TC 16 Z9 16 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 1 PY 1996 VL 93 IS 9 BP 1677 EP 1684 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA UG813 UT WOS:A1996UG81300016 PM 8653873 ER PT J AU Basta, M AF Basta, M TI Modulation of complement-mediated immune damage by intravenous immune globulin SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article; Proceedings Paper CT Symposium on Intravenous Immune Globulin - Mechanisms of Action and Model Disease States CY JUN 09-19, 1995 CL GENEVA, SWITZERLAND DE complement; immune globulin therapy; immunomodulation ID IDIOPATHIC THROMBOCYTOPENIC PURPURA; GAMMA-GLOBULIN; KAWASAKI SYNDROME; IMMUNOGLOBULIN; INVITRO; INVIVO; ACTIVATION; CLEARANCE; REVERSAL AB High-dose intravenous immune globulin (IVIG) exerts a beneficial effect in a variety of immune disorders. One possible underlying mechanism of this effect could be interference with the complement system. This conclusion was based on the results obtained in animal models of complement-mediated pathology, in vitro complement assays and studies on related human diseases. Clearance of IgM-sensitized erythrocytes was specifically suppressed by IVIG treatment. The same therapy prevented pulmonary endothelial cell lesions, the hallmark of Forssman shock, in 75% of animals. All control animals, either untreated or injected with control reagents, died within minutes following induction of Forssman shock. In vitro uptake of C3b and C4b complement fragments on to corpusculate immune complexes was significantly inhibited by IVIG. Studies that involved patients suffering from disorders with pathogenesis similar to animal models of complement-mediated immune injury fully supported the hypothesis that IVIG interacts with activated complement components and prevents their deposition on target cells. The author's results suggest that IVIG can be an effective modulator of inappropriate complement attack. RP Basta, M (reprint author), NIAID,CLIN INVEST LAB,NIH,BLDG 10,ROOM 4N248,BETHESDA,MD 20892, USA. OI Basta, Milan/0000-0001-5958-9241 NR 19 TC 58 Z9 59 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD MAY PY 1996 VL 104 SU 1 BP 21 EP 25 PG 5 WC Immunology SC Immunology GA UH607 UT WOS:A1996UH60700005 PM 8625538 ER PT J AU Young, NS AF Young, NS TI Parvovirus infection and its treatment SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article; Proceedings Paper CT Symposium on Intravenous Immune Globulin - Mechanisms of Action and Model Disease States CY JUN 09-19, 1995 CL GENEVA, SWITZERLAND DE red cell aplasia; sickle cell disease; immune globulin; fifth disease; immunodeficiency ID RED-CELL APLASIA; B19 PARVOVIRUS; CHRONIC ANEMIA; ACUTE-LEUKEMIA; IMMUNOGLOBULIN; REGION; VIRUS; IMMUNODEFICIENCY; IDENTIFICATION; B19-PARVOVIRUS AB B19 parvovirus is an important pathogen in man. Acute infection produces fifth disease (erythema infectiosum) in normal individuals, transient aplastic crisis in the patient with haemolysis, and pure red cell aplasia in the immunologically incompetent host. Fetal infection can lead to hydrops fetalis. The target cell of the virus is the marrow erythroid progenitor. The immune response to the virus is largely humoral and directed against limited numbers of epitopes. Persistent infection is due to failure to produce neutralizing antibodies. Because viral infection is prevalent in the population, therapeutic immune globulin preparations are a good source of anti-Bls antibodies. IgG administration can lead to cure of anaemia in the congenitally immunodeficient patient and to its amelioration in AIDS patients with persistent parvovirus infection. RP Young, NS (reprint author), NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892, USA. NR 31 TC 42 Z9 45 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD MAY PY 1996 VL 104 SU 1 BP 26 EP 30 PG 5 WC Immunology SC Immunology GA UH607 UT WOS:A1996UH60700006 PM 8625539 ER PT J AU Dalakas, MC AF Dalakas, MC TI Clinical benefits and immunopathological correlates of intravenous immune globulin in the treatment of inflammatory myopathies SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article; Proceedings Paper CT Symposium on Intravenous Immune Globulin - Mechanisms of Action and Model Disease States CY JUN 09-19, 1995 CL GENEVA, SWITZERLAND DE inflammatory myopathies; polymyositis; dermatomyositis; inclusion-body myositis; intravenous immune globulin ID INCLUSION-BODY MYOSITIS; MEDIATED CYTO-TOXICITY; CONTROLLED TRIAL; GAMMA-GLOBULIN; DERMATOMYOSITIS; POLYMYOSITIS; EXPRESSION; THERAPY; CELLS AB High-dose intravenous immune globulin (IVIG) is emerging as a promising therapy for patients with inflammatory myopathies who have become unresponsive to, or cannot tolerate, conventional therapies. In a double-blind, placebo-controlled study, using objective criteria for improvement, IVIG demonstrated moderate to dramatic improvement in 75% of the patients with dermatomyositis. Preliminary results from a controlled study in inclusion-body myositis show that IVIG may also exert a mild benefit, but only in a small number of patients and in certain muscle groups. In some patients with polymyositis, IVIG is reported to be of benefit but controlled studies have not yet been completed. Immunocytochemical, immunological and in vitro studies on the patients' repeated muscle biopsies and follow-up sera showed that IVIG exert its action in inflammatory myopathies by: (i) inhibiting myotoxic cytokines, such as TNF-alpha and IL-1; (ii) blockade of Fc receptors on endomysial macrophages interfering with Fc receptor-mediated phagocytosis; and (iii) inhibiting the uptake of C3 and intercepting the formation and deposition of membranolytic attack complex on the endomysial capillaries. RP Dalakas, MC (reprint author), NINCDS,NEUROMUSCULAR DIS SECT,MED NEUROL BRANCH,NIH,BLDG 10,ROOM 4N248,10 CTR DR,MSC 1382,BETHESDA,MD 20892, USA. NR 35 TC 26 Z9 26 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD MAY PY 1996 VL 104 SU 1 BP 55 EP 60 PG 6 WC Immunology SC Immunology GA UH607 UT WOS:A1996UH60700011 PM 8625545 ER PT J AU Danforth, DN Sgagias, MK AF Danforth, DN Sgagias, MK TI Tumor necrosis factor alpha enhances secretion of transforming growth factor beta(2) in MCF-7 breast cancer cells SO CLINICAL CANCER RESEARCH LA English DT Article ID DIFFERENTIAL REGULATION; INHIBIT GROWTH; MESSENGER-RNA; RETINOIC ACID; FACTOR-BETA-1; EXPRESSION; ESTRADIOL; INDUCTION; INTERLEUKIN-1-ALPHA; KERATINOCYTES AB We studied the effect of tumor necrosis factor alpha (TNF-alpha) on transforming growth factor beta (TGF-beta) secretion by human breast cell lines to further characterize the antitumor effects of TNF-alpha. We found that TNF-alpha increased the secretion of TGF-P in two established breast cancer cell lines (MCF-7 and ZR-75-1) but not in two immortalized human mammary epithelial cell lines (184B5 and MCF-10A). In MCF-7 cells, TNF-alpha increased the secretion of total TGF-beta 6.1-fold within 72 h in a dose-dependent manner, The secretion of both latent and active forms of TGF-beta was increased, and their ratio altered from 25:1 to 12:1 in the medium, TNF-alpha converted the secretory pattern of TGF-beta by MCF-7 cells from the heterodimeric form TGF-beta(1.2) to the homodimeric form TGF-beta(2). Immunoblot analysis under nonreducing conditions identified four molecular mass species of TGF-beta secreted in the culture media of untreated MCF-7 cells (238, 210, 40-55, and 25 kDa), Under reducing conditions, three molecular mass species of TGF-beta were identified: 88, 44, and 12 kDa, Gel filtration analysis demonstrated that the secreted TGF-beta within the range of 12-88 kDa was biologically active. TNF-alpha treatment did not alter the size of molecular mass species secreted by MCF-7 cells and did not change steady-state levels of mRNA for TGF-beta(1) or TGF-beta(2). These findings indicate that TNF-alpha may regulate quantitatively and qualitatively TGF-beta secretion by human breast cancer cells in vitro. Tbe diverse biological activities of TGF-beta may also allow TNF-alpha to regulate the growth and metabolism of human mammary epithelial cells and/or stromal cells in a paracrine manner. RP Danforth, DN (reprint author), NCI,SURG BRANCH,NIH,BLDG 10,ROOM 2B38,BETHESDA,MD 20892, USA. NR 33 TC 15 Z9 15 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 1996 VL 2 IS 5 BP 827 EP 835 PG 9 WC Oncology SC Oncology GA UJ856 UT WOS:A1996UJ85600007 PM 9816237 ER PT J AU Shack, S Miller, A Liu, L Prasanna, P Thibault, A Samid, D AF Shack, S Miller, A Liu, L Prasanna, P Thibault, A Samid, D TI Vulnerability of multidrug-resistant tumor cells to the aromatic fatty acids phenylacetate and phenylbutyrate SO CLINICAL CANCER RESEARCH LA English DT Article ID BREAST-CANCER-CELLS; ERYTHROID-DIFFERENTIATION; P-GLYCOPROTEIN; AGENTS; LINES; EXPRESSION; MODULATION; INVITRO; GROWTH; GENE AB Cytotoxic chemotherapies often give rise to multidrug resistance, which remains a major problem in cancer management, In pursuit of alternative treatments for chemoresistant tumor cells, we tested the response of multi-drug-resistant (MDR) tumor cell lines to the aromatic fatty acids phenylacetate (PA) and phenylbutyrate (PB), two differentiation inducers currently in clinical trials, Both compounds induced cytostasis and maturation of multidrug-resistant breast, ovarian, and colon carcinoma cells with no significant effect on cell viability, In contrast to their poor response to doxorubicin, the MDR cells were generally more sensitive to growth arrest by PA and PB than their parental counterparts. The aromatic fatty acids, like the differentiation-inducing aliphatic fatty acid butyrate, up-regulated mdr-1 gene expression. However, while butyrate increased multidrug resistance, PA and PB potentiated the cytotoxic activity of doxorubicin against MDR cells, The latter was associated with time-dependent declines in glutathione levels and in the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione S-transferase, the antioxidant enzymes implicated in cell resistance to free radical-based therapies, Taken together, our in vitro data indicate that PA and PB, differentiation inducers of the aromatic fatty acid class, may provide an alternative approach to the treatment of MDR tumors. C1 UNIV VIRGINIA,CTR CANC,CHARLOTTESVILLE,VA 22908. NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. ARMED FORCES RADIOBIOL RES INST,RADIAT BIOCHEM DEPT,BETHESDA,MD 20889. NR 35 TC 38 Z9 40 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 1996 VL 2 IS 5 BP 865 EP 872 PG 8 WC Oncology SC Oncology GA UJ856 UT WOS:A1996UJ85600012 PM 9816242 ER PT J AU Ciernik, IF Berzofsky, JA Carbone, DP AF Ciernik, IF Berzofsky, JA Carbone, DP TI Human lung cancer cells endogenously expressing mutant p53 process and present the mutant epitope and are lysed by mutant-specific cytotoxic T lymphocytes SO CLINICAL CANCER RESEARCH LA English DT Article ID RAS PROTOONCOGENES; GENE; RECOGNITION; PROTEIN; PEPTIDE AB The p53 oncoprotein frequently contains somatically acquired missense mutations and is often overexpressed in cancer cells, Missense mutations can give rise to new tumor-specific peptide sequences, which can act as targets for T-cell-mediated immunotherapy. To investigate the ability of human lung cancer cells to adequately process and present a mutant p53-derived CTL epitope, we transfected the human cell line HMy-2.C1R and the p53-null human lung cancer cell lines H358 and H1299 with an expression vector containing a human mutant p53 (135 Cys to Tyr), After transfection with the K-d restriction element, these cells were tested as targets for murine mutation-specific CTLs. We show that these human lung cancer cells effectively process and present this endogenous mutant human p53 epitope, resulting in efficient, mutant epitope-specific lysis by CTLs, In the presence of the appropriate restriction element, human lung cancer cells can be effectively targeted by CTLs specific for somatically acquired, endogenous mutant epitopes, supporting targeted immunotherapy efforts in lung cancer. C1 UNIV TEXAS,SW MED CTR,SIMMONS CANC CTR,DALLAS,TX 75235. NCI,METAB BRANCH,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [R01 CA61242, R01 CA57856] NR 25 TC 16 Z9 16 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 1996 VL 2 IS 5 BP 877 EP 882 PG 6 WC Oncology SC Oncology GA UJ856 UT WOS:A1996UJ85600014 PM 9816244 ER PT J AU Niemela, JE Snader, BM Elin, RJ AF Niemela, JE Snader, BM Elin, RJ TI Determination of ionized magnesium in platelets and correlation with selected variables SO CLINICAL CHEMISTRY LA English DT Article DE fluorometry; FURAPTRA; cholesterol ID INTRACELLULAR FREE MAGNESIUM; CYTOSOLIC FREE MAGNESIUM; TRANSPORT; FLUORESCENCE; CELLS AB We describe a method for determining the intracellular ionized magnesium concentration ([Mg2+](i)) in platelets by using the fluorescent probe FURAPTRA. We determined the dissociation constant (K-D) of FURAPTRA for Mg2+ (2.26 +/- 0.29 mmol/L), within-day assay variability (CV = 6.8%), among-day intraindividual variability (CV = 11.0%), variability after a 4-h delay in processing the blood specimen (t = 1.2, P >0.2; F = 6.2, P <0.02), and the reference interval (0.23-0.59 mmol/L) for this assay. We also evaluated the correlation between platelet [Mg2+](i) and concentrations of selected serum electrolytes, proteins, and total cholesterol; age; body mass index; and gender. Only the inverse correlation between platelet [Mg2+](i) and serum total cholesterol concentration in men was significant (r = -0.66, P <0.005). C1 NIH,DEPT CLIN PATHOL,WARREN GRANT MAGNUSON CLIN CTR,BETHESDA,MD 20892. OI Niemela, Julie/0000-0003-4197-3792 NR 26 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAY PY 1996 VL 42 IS 5 BP 744 EP 748 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA UJ253 UT WOS:A1996UJ25300016 PM 8653901 ER PT J AU Hiemenz, JW Walsh, TJ AF Hiemenz, JW Walsh, TJ TI Lipid formulations of amphotericin B: Recent progress and future directions SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Focus on Fungal Infections 5 Meeting CY MAR 09-10, 1995 CL SAN FRANCISCO, CA SP Janssen Pharmaceutica, Roerig, Div Pfizer Pharm ID INVASIVE FUNGAL-INFECTIONS; DEOXYCHOLATE SUSPENSION; COLLOIDAL DISPERSION; IMMUNOCOMPROMISED PATIENTS; TRANSPLANT RECIPIENTS; MURINE CRYPTOCOCCOSIS; NEUTROPENIC PATIENTS; ANTIFUNGAL ACTIVITY; DRUG DELIVERY; PHARMACOKINETICS AB Three lipid formulations of amphotericin B are now either marketed for clinical use or undergoing further study before they can be approved in various countries worldwide. Amphotericin B lipid complex (ABLC; Abelcet, Liposome Company, Princeton, NJ) is a concentration of ribbonlike structures of a bilayered membrane formed by combining a 7:3 molar ratio of dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol with amphotericin B, Amphotericin B colloidal dispersion (ABCD; Amphocil, Sequus Pharmaceuticals, Menlo Park, CA) is composed of disklike structures of cholesteryl sulfate complexed with amphotericin B. AmBisome (Nexstar, San Dimas, CA), the only true liposomal amphotericin B, consists of small unilamellar vesicles made up of a bilayer membrane of hydrogenated soy phosphatidylcholine and distearoylphosphatidylglycerol stabilized with cholesterol in a 2:0.8:1 ratio combined with amphotericin B, All of the preparations appear to be preferentially accumulated in organs of the reticuloendothelial system, as opposed to the kidney. In vivo animal models as well as current clinical experience suggest that use of these formulations results in overall improvement in the therapeutic index. Patients with life-threatening mycosis for whom therapy has failed or who are intolerant to therapy with amphotericin B deoxycholate have been successfully treated with these formulations, However, further study is warranted to help clarify the usefulness of each of the lipid formulations as first-line therapy for documented or suspected invasive fungal infections. C1 UNIV S FLORIDA,H LEE MOFFITT CANC CTR & RES INST,DIV TROP MED,TAMPA,FL 33612. NCI,NIH,INFECT DIS SECT,BETHESDA,MD 20892. RP Hiemenz, JW (reprint author), UNIV S FLORIDA,H LEE MOFFITT CANC CTR & RES INST,DIV BONE MARROW TRANSPLANTAT INFECT DIS,TAMPA,FL 33612, USA. NR 86 TC 205 Z9 212 U1 0 U2 12 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY PY 1996 VL 22 SU 2 BP S133 EP S144 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UH601 UT WOS:A1996UH60100010 PM 8722841 ER PT J AU Andrich, MP Cawley, M Chen, CC AF Andrich, MP Cawley, M Chen, CC TI Artifacts caused by nonionic contrast media and a Portacath on a dual-energy x-ray absorptiometry whole-body composition study SO CLINICAL NUCLEAR MEDICINE LA English DT Article C1 NIH,DEPT NUCL MED,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892. NR 2 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD MAY PY 1996 VL 21 IS 5 BP 407 EP 408 DI 10.1097/00003072-199605000-00017 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UH910 UT WOS:A1996UH91000017 PM 8732843 ER PT J AU Jacobs, MC Goldstein, DS Willemsen, JJ Smits, P Thien, T Lenders, JWM AF Jacobs, MC Goldstein, DS Willemsen, JJ Smits, P Thien, T Lenders, JWM TI Differential effects of low- and high-intensity lower body negative pressure on noradrenaline and adrenaline kinetics in humans SO CLINICAL SCIENCE LA English DT Article DE adrenaline; baroreceptors; cardiopulmonary; lower body negative pressure; noradrenaline ID VASOCONSTRICTOR RESPONSES; SKELETAL-MUSCLE; LEG MUSCLES; CARDIOPULMONARY; CIRCULATION; ACTIVATION AB 1. Lower body negative pressure provides a means to examine neurocirculatory reflexive responses to decreases in venous return to the heart, We assessed whether the pattern of catecholaminergic responses to lower body negative pressure depends on the intensity of the stimulus (-15 versus -40 mmHg), 2. In 14 healthy subjects, responses of forearm blood flow and noradrenaline spillover and of total body noradrenaline and adrenaline spillover were assessed during infusion of [H-3]noradrenaline and [H-3]adrenaline during -15 and -40 mmHg of lower body negative pressure, 3. During lower body negative pressure at -15 mmHg, heart rate and pulse pressure did not change, but forearm vascular resistance increased by 25-50%. Forearm noradrenaline spillover increased by about 50%, from 0.63 +/- 0.16 to 0.94 +/- 0.23 pmol min(-1) 100 ml(-1) (P < 0.05), Total body noradrenaline spillover did not change, and total body adrenaline spillover increased significantly by about 30%. Clearances of noradrenaline and adrenaline were unchanged, 4. During lower body negative pressure at -40 mmHg, heart rate increased and pulse pressure decreased, Forearm vascular resistance increased by about 100%, and forearm noradrenaline spillover increased by 80%, from 0.73 +/- 0.19 to 1.32 +/- 0.36 pmol min(-1) 100 ml(-1) (P < 0.05), Total body noradrenaline spillover increased by 30%, and total body adrenaline spillover increased by about 50%, Clearances of both noradrenaline and adrenaline decreased, 5. The results are consistent with the view that selective deactivation of cardiopulmonary baroreceptors during low-intensity lower body negative pressure increases sympathoneural traffic to forearm skeletal muscle and increases adrenomedullary secretion without a concomitant generalized increase in sympathoneural outflows, Concurrent deactivation of cardiopulmonary and arterial baroreceptors during high-intensity lower body negative pressure evokes a more generalized increase in sympathoneural activity, accompanied by further increased adrenomedullary secretion and decreased plasma clearances of noradrenaline and adrenaline, The findings support differential increases in skeletal sympathoneural and adrenomedullary outflows during orthostasis, with more generalized sympathoneural responses to systemic hypotension. C1 UNIV NIJMEGEN ST RADBOUD HOSP,DIV GEN INTERNAL MED,DEPT INTERNAL MED,DEPT MED,6525 GA NIJMEGEN,NETHERLANDS. NINCDS,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. UNIV NIJMEGEN ST RADBOUD HOSP,DEPT EXPTL & CHEM ENDOCRINOL,6525 GA NIJMEGEN,NETHERLANDS. RI Lenders, J.W.M./L-4487-2015; Smits, P.A.B.M./E-2889-2015 NR 18 TC 19 Z9 19 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0143-5221 J9 CLIN SCI JI Clin. Sci. PD MAY PY 1996 VL 90 IS 5 BP 337 EP 343 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UL137 UT WOS:A1996UL13700002 PM 8665770 ER PT J AU Wilbur, WJ Yang, YM AF Wilbur, WJ Yang, YM TI An analysis of statistical term strength and its use in the indexing and retrieval of molecular biology texts SO COMPUTERS IN BIOLOGY AND MEDICINE LA English DT Article DE molecular biology; stop terms; text retrieval; text classification; linear least squares fit; weight; strength; vector model; Bayesian model AB The biological literature presents a difficult challenge to information processing in its complexity, diversity, and in its sheer volume. Much of the diversity resides in its technical terminology, which has also become voluminous. In an effort to deal more effectively with this large vocabulary and improve information processing, a method of focus has been developed which allows one to classify terms based on a measure of their importance in describing the content of the documents in which they occur. The measurement is called the strength of a term and is a measure of how strongly the term's occurrences correlate with the subjects of documents in the database. If term occurrences are random then there will be no correlation and the strength will be zero, but if for any subject, the term is either always present or never present its strength will be one. We give here a new, information theoretical interpretation of term strength, review some of its uses in focusing the processing of documents for information retrieval and describe new results obtained in document categorization. Copyright (C) 1996 Elsevier Science Ltd. C1 MAYO CLIN & MAYO FDN,SECT MED INFORMAT RESOURCES,ROCHESTER,MN 55905. RP Wilbur, WJ (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20894, USA. NR 31 TC 58 Z9 59 U1 2 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0010-4825 J9 COMPUT BIOL MED JI Comput. Biol. Med. PD MAY PY 1996 VL 26 IS 3 BP 209 EP 222 DI 10.1016/0010-4825(95)00055-0 PG 14 WC Biology; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Computer Science; Engineering; Mathematical & Computational Biology GA UN160 UT WOS:A1996UN16000004 PM 8725772 ER PT J AU Pollack, MM Patel, KM Ruttimann, UE AF Pollack, MM Patel, KM Ruttimann, UE TI PRISM III: An updated pediatric risk of mortality score SO CRITICAL CARE MEDICINE LA English DT Article DE severity of illness index; mortality prediction; pediatrics; critical illness; patient outcome assessment; intensive care unit; pediatric ID INTENSIVE-CARE UNITS; ILL HOSPITALIZED ADULTS; ACUTE PHYSIOLOGY; PREDICTION; SEVERITY; MODEL AB Objectives: The relationship between physiologic status and mortality risk should be reevaluated as new treatment protocols, therapeutic interventions, and monitoring strategies are introduced, and as patient populations change. We developed and validated a third-generation pediatric physiology based score for mortality risk, Pediatric Risk of Mortality III (PRISM III). Design: Prospective cohort. Setting: There were 32 pediatric intensive care units (ICUs): 16 pediatric ICUs were randomly chosen and 16 volunteered. Patients: Consecutive admissions at each site were included until at least 11 deaths per site occurred. Measurements and Main Results: Physiologic data included the most abnormal values from the first 12 and the second 12 hrs of ICU stay. Outcomes and descriptive data were also collected. Physiologic variables where normal values change with age were stratified by age (neonate, infant, child, adolescent). The database was randomly split into development (90%) and validation (10%) sets. Variables and their ranges were chosen by computing the risk of death (odds ratios) relative to the midrange of survivors for each physiologic variable. Univariate and multivariate statistical procedures, including multiple logistic regression analysis, were used to develop the PRISM III score and mortality risk predictors. Data were collected on 11,165 admissions (543 deaths). The PRISM III score has 17 physiologic variables subdivided into 26 ranges. The variables most predictive of mortality were minimum systolic blood pressure, abnormal pupillary reflexes, and stupor/coma. Other risk factors, including two acute and two chronic diagnoses, and four additional risk factors, were used in the final predictors. The PRISM III score and the additional risk factors were applied to the first 12 hrs of stay (PRISM III-12) and the first 24 hrs of stay (PRISM III-24). The Hosmer-Lemeshow chi square goodness-of-fit evaluations demonstrated absence of significant calibration errors (p values: PRISM III-12 development = .2496; PRISM III-24 development = .1374; PRISM III-12 validation = .4168; PRISM III-24 validation = .5504). The area under the receiver operating curve and Flora's z-statistic indicated excellent discrimination and accuracy (area under the receiver operating curve - PRISM III-12 development 947 +/- 0.007; PRISM III-24 development 0.958 +/- 0.006; PRISM III-12 validation 0.941 +/- 0.021; PRISM III-24 validation 0.944 +/- 0.021; Flora's z-statistic - PRISM III-12 validation = .7479; PRISM III-24 validation = .9225), although generally, the PRISM III-24 performed better than the PRISM III-12 models. Excellent good ness of fit was also found for patient groups stratified by age (significance levels: PRISM III-12 = .1622; PRISM III-24 = .4137), and by diagnosis (significance levels: PRISM III-12 = .5992; PRISM III-24 = .7939). Conclusions: PRISM III resulted in several improvements over the original PRISM. Reassessment of physiologic variables and their ranges, better age adjustment for selected variables, and additional risk factors resulted in a mortality risk model that is more accurate and discriminates better. The large number of diverse ICUs in the database indicates PRISM III is more likely to be representative of United States units. C1 GEORGE WASHINGTON UNIV,SCH MED,DEPT ANESTHESIOL,WASHINGTON,DC. GEORGE WASHINGTON UNIV,SCH MED,DEPT PEDIAT,WASHINGTON,DC. NIAAA,NIH,WASHINGTON,DC. RP Pollack, MM (reprint author), CHILDRENS NATL MED CTR,CTR HLTH SERV & CLIN RES,CHILDRENS RES INST,111 MICHIGAN AVE NW,WASHINGTON,DC 20010, USA. NR 26 TC 630 Z9 658 U1 2 U2 12 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 1996 VL 24 IS 5 BP 743 EP 752 DI 10.1097/00003246-199605000-00004 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA UL402 UT WOS:A1996UL40200004 PM 8706448 ER PT J AU Grabowski, GA Saal, HM Wenstrup, RJ Barton, NW AF Grabowski, GA Saal, HM Wenstrup, RJ Barton, NW TI Gaucher disease: A prototype for molecular medicine SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review ID ACID BETA-GLUCOSIDASE; HUMAN GLUCOCEREBROSIDASE GENE; ENZYME REPLACEMENT THERAPY; SPHINGOLIPID ACTIVATOR PROTEIN-2; BONE-MARROW TRANSPLANTATION; MACROPHAGE-TARGETED GLUCOCEREBROSIDASE; CARBOHYDRATE RECOGNITION SYSTEMS; PHENOTYPE-GENOTYPE CORRELATIONS; LYSOSOMAL STORAGE DISEASE; SITE-DIRECTED MUTAGENESIS C1 UNIV CINCINNATI, COLL MED, DEPT PEDIAT, CINCINNATI, OH USA. UNIV CINCINNATI, COLL MED, DEPT MOLEC GENET BIOCHEM & MICROBIOL, CINCINNATI, OH USA. NINCDS, NIH,DEV & METAB NEUROL BRANCH,CLIN INVEST SECT, DEV & METAB NEUROL BRANCH, BETHESDA, MD 20892 USA. RP Grabowski, GA (reprint author), CHILDRENS HOSP, MED CTR, DIV HUMAN GENET, 3333 BURNET AVE, CINCINNATI, OH 45229 USA. NR 313 TC 21 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD MAY PY 1996 VL 23 IS 1 BP 25 EP 55 DI 10.1016/1040-8428(96)00199-0 PG 31 WC Oncology; Hematology SC Oncology; Hematology GA UW368 UT WOS:A1996UW36800002 PM 8817081 ER PT J AU Nelson, CE Morgan, BA Burke, AC Laufer, E DiMambro, E Murtaugh, LC Gonzales, E Tessarollo, L Parada, LF Tabin, C AF Nelson, CE Morgan, BA Burke, AC Laufer, E DiMambro, E Murtaugh, LC Gonzales, E Tessarollo, L Parada, LF Tabin, C TI Analysis of Hox gene expression in the chick limb bud SO DEVELOPMENT LA English DT Article DE Hox; limb; pattern; chick; Sonic hedgehog ID HOMEOBOX GENE; HOMEOTIC TRANSFORMATIONS; MOUSE EMBRYOS; PATTERN-FORMATION; RETINOIC ACID; XENOPUS; MORPHOGENESIS; TRANSGENE; EVOLUTION; PROTEIN AB The vertebrate Hox genes have been shown to be important for patterning the primary and secondary axes of the developing vertebrate embryo. The function of these genes along the primary axis of the embryo has been generally interpreted in the context of positional specification and homeotic transformation of axial structures. The way in which these genes are expressed and function during the development of the secondary axes, particularly the limb, is less clear. In order to provide a reference for understanding the role of the Hox genes in limb patterning, we isolated clones of 23 Hox genes expressed during limb development, characterized their expression patterns and analyzed their regulation by the signalling centers which pattern the limb. The expression patterns of the Abd-B-related Hoxa and Herd genes have previously been partially characterized; however, our study reveals that these genes are expressed in patterns more dynamic and complex than generally appreciated, only transiently approximating simple, concentric, nested domains. Detailed analysis of these patterns suggests that the expression of each of the Nora and Herd genes is regulated in up to three independent phases. Each of these phases appears to be associated with the specification and patterning of one of the proximodistal segments of the limb (upper arm, lower arm and hand). Interestingly, in the last of these phases, the expression of the Herd genes violates the general rule of spatial and temporal colinearity of Hox gene expression with gene order along the chromosome. In contrast to the Abd-B-related Horn and Herd genes, which are expressed in both the fore and hind limbs, different sets of Hoxc genes are expressed in the two limbs. There is a correlation between the relative position of these genes along the chromosome and the axial level of the limb bud in which they are expressed. The more 3' genes are expressed in the fore limb bud while the 5' genes are expressed in the hind limb bud; intermediate genes are transcribed in both limbs, However, there is no clear correlation between the relative position of the genes along the chromosome and their expression domains within the limb. With the exception of Hoxc-11, which is transcribed in a posterior portion of the hind limb, Hoxc gene expression is restricted to the anterior/proximal portion of the limb bud. Importantly, comparison of the distributions of Hoxc-6 RNA and protein products reveals posttranscriptional regulation of this gene, suggesting that caution must be exercised in interpreting the functional significance of the RNA distribution of any of the vertebrate Hox genes. To understand the genesis of the complex patterns of Hox gene expression in the limb bud, we examined the propagation of Hox gene expression relative to cell proliferation. We find that shifts in Hox gene expression cannot be attributed to passive expansion due to cell proliferation. Rather, phase-specific Hox gene expression patterns appear to result from a context-dependent response of the limb mesoderm to Sonic hedgehog. Sonic hedgehog (the patterning signal from the Zone of Polarizing Activity) is known to be able to activate Herd gene expression in the limb. Although we find that Sonic hedgehog is capable of initiating and polarizing Herd gene expression during both of the latter two phases of Hox gene expression, the specific patterns induced are not determined by the signal, hut depend upon the temporal context of the mesoderm receiving the signal. Misexpression of Sonic hedgehog also reveals that Hoxb-9, which is normally excluded from the posterior mesenchyme of the leg, is negatively regulated by Sonic hedgehog and that Hoxc-11, which is expressed in the posterior portion of the leg, is not affected by Sonic hedgehog and hence is not required to pattern the skeletal elements of the lower leg. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,CHARLESTOWN,MA 02129. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOL EMBRYOL SECT,FREDERICK,MD 21702. UNIV TEXAS,SW MED CTR,CTR DEV BIOL,DALLAS,TX 75235. RI Parada, luis/B-9400-2014; OI Laufer, Edward/0000-0002-4933-1017 NR 62 TC 375 Z9 384 U1 1 U2 19 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD MAY PY 1996 VL 122 IS 5 BP 1449 EP 1466 PG 18 WC Developmental Biology SC Developmental Biology GA UM558 UT WOS:A1996UM55800011 PM 8625833 ER PT J AU Stolow, MA Shi, YB AF Stolow, MA Shi, YB TI A role for xenopus sonic hedgehog in adult epithelial morphogenesis of the intestine during metamorphosis. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAY 1 PY 1996 VL 175 IS 2 BP 81 EP 81 PG 1 WC Developmental Biology SC Developmental Biology GA UK435 UT WOS:A1996UK43500137 ER PT J AU Feltner, DE Hermesz, E Grinberg, A Mahon, KA AF Feltner, DE Hermesz, E Grinberg, A Mahon, KA TI Targeted disruption or the mouse Rpx homcobox gene SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NICHHD,LAB MAMMALIAN GENES & DEV,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAY 1 PY 1996 VL 175 IS 2 BP 110 EP 110 PG 1 WC Developmental Biology SC Developmental Biology GA UK435 UT WOS:A1996UK43500166 ER PT J AU Baek, KH Fabian, JR Sprenger, F Morrison, DK Ambrosio, L AF Baek, KH Fabian, JR Sprenger, F Morrison, DK Ambrosio, L TI The activity of D-raf in Torso signal transduction is altered by serine substitution, N-terminal deletion, and membrane targeting SO DEVELOPMENTAL BIOLOGY LA English DT Article ID PROTEIN-KINASE; DROSOPHILA EMBRYO; TYROSINE KINASE; PHOSPHORYLATION; ONCOGENE; RECEPTOR; EXPRESSION; MELANOGASTER; REQUIREMENT; ACTIVATION AB The Raf family of serine/threonine kinases are essential components in many receptor tyrosine kinase-mediated signal transduction pathways. Here, we analyze the function of D-raf in the Torso (Tor) pathway required to specify cellular fates at the embryonic poles. Using mutant embryos lacking endogenous D-raf protein, we show that D-raf's serine/threonine kinase activity is essential for its role in Tor signal transduction and that human Raf-l will substitute for D-raf in this pathway. After Tor activation, D-raf becomes hyperphosphorylated. We identified two putative serine phosphorylation sites (S388 and S743) in SF9 cells and demonstrate that S743 or its phosphorylation is essential for D-raf function in embryos. Alanine substitution at S388, N-terminal truncation, or targeted membrane association permits transmission of the Torso signal by D-raf, but these D-raf molecules differ in their rescuing potential and relative biological activity. Membrane-targeted D-raf(tor4021) showed the highest level of activity, followed by alanine-substituted D-raf(S388A) and N-terminal-truncated D-raf(Delta 445). Since the activity profiles for these altered forms of D-raf are distinct, these findings indicate that each structural modification differentially affects the regulation and/or propagation of the Tor signal by these mutant D-raf proteins. (C) 1996 Academic Press, Inc. C1 IOWA STATE UNIV SCI & TECHNOL,DEPT ZOOL & GENET,SIGNAL TRANSDUCT TRAINING GRP,AMES,IA 50011. NCI,MOL MECHANISMS CARCINOGENESIS LAB,ABL BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. UNIV CALIF SAN FRANCISCO,DEPT BIOCHEM & BIOPHYS,SAN FRANCISCO,CA 94143. OI Baek, Kwang-Hyun/0000-0001-7662-7190 FU PHS HHS [N01-C0-46000] NR 85 TC 20 Z9 20 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAY 1 PY 1996 VL 175 IS 2 BP 191 EP 204 DI 10.1006/dbio.1996.0107 PG 14 WC Developmental Biology SC Developmental Biology GA UK435 UT WOS:A1996UK43500001 PM 8626025 ER PT J AU MontroseRafizadeh, C Yang, H Pritchette, LA Eng, J AF MontroseRafizadeh, C Yang, H Pritchette, LA Eng, J TI Structure function analysis of exendin-4/GLP-1 analogs SO DIABETES LA English DT Meeting Abstract C1 NIA,BALTIMORE,MD 21224. VET ADM MED CTR,BRONX,NY 10468. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 1996 VL 45 SU 2 BP 553 EP 553 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UJ883 UT WOS:A1996UJ88300549 ER PT J AU Maffei, M Stoffel, M Barone, M Moon, B Dammerman, M Ravussin, E Bogardus, C Ludwig, DS Flier, JS Talley, M Auerbach, S Friedman, JM AF Maffei, M Stoffel, M Barone, M Moon, B Dammerman, M Ravussin, E Bogardus, C Ludwig, DS Flier, JS Talley, M Auerbach, S Friedman, JM TI Absence of mutations in the human OB gene in obese diabetic subjects SO DIABETES LA English DT Article ID MICE AB The product of the obese (ob) gene, leptin, is a secreted protein that is important in the regulation of body weight. Mice with mutations in the ob gene are obese and diabetic and manifest reduced physical as well as metabolic activity. In this study, we tested the possibility that mutations tin the OB gene may contribute to human obesity, We report the isolation and partial sequence of the human OB gene and the screening of 105 obese patients for mutations in the protein coding sequence using the technique of single-strand conformational polymorphism. No coding sequence polymorphism was found, suggesting that mutations in the coding sequence of the OB gene do not constitute a common cause of increased body weight in humans, We also identified a highly polymorphic simple dinucleotide repeat DNA polymorphism in this gene that will be useful for genetic studies. C1 ROCKEFELLER UNIV,HOWARD HUGHES MED INST,DEPT GENET,NEW YORK,NY 10021. US PHS,NEW YORK,NY. HOWARD HUGHES MED INST,DEPT GENET,COCONUT GROVE,FL. NIDDKD,CLIN DIABET & NUTR SECT,NIH,PHOENIX,AZ 85016. BETH ISRAEL HOSP,DEPT ENDOCRINOL,BOSTON,MA 02215. FU NIDDK NIH HHS [DK-41096] NR 14 TC 165 Z9 167 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 1996 VL 45 IS 5 BP 679 EP 682 DI 10.2337/diabetes.45.5.679 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UJ231 UT WOS:A1996UJ23100023 PM 8621022 ER PT J AU Reed, DR Ding, Y Xu, WZ Cather, C Green, ED Price, RA AF Reed, DR Ding, Y Xu, WZ Cather, C Green, ED Price, RA TI Extreme obesity may be linked to markers flanking the human OB gene SO DIABETES LA English DT Article AB Mice with mutations of the ob gene are extremely obese, and the human homologue (OB) has been cloned and physically mapped, The protein product of the ob gene (leptin) reduces body fat in mice when given exogenously, and leptin has been proposed to provide a lipostatic signal that regulates adiposity, Variation in the OB gene may be one genetically determined cause of obesity in human populations, To test this hypothesis, we genotyped siblings from 78 families at markers flanking the human OB gene, Pairs of siblings with extreme obesity (BMI greater than or equal to 40; n = 59) shared haplotypes identical-by-descent for the region containing the OB gene at greater than chance levels (corrected P = 0.04), Furthermore, one haplotype containing the OB gene was transmitted by heterozygous parents to extremely obese (BMI greater than or equal to 40) offspring more frequently than expected by chance, indicting significant allelic disequilibrium (corrected P = 0.027), One explanation for these linkage findings is that some individuals with extreme obesity have an allelic variant of the OB gene, although other nearby genes could contribute to obesity in these families. C1 UNIV PENN,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. CHILDRENS HOSP,DEPT NEUROL,PHILADELPHIA,PA 19104. RUTGERS STATE UNIV,DEPT PSYCHOL,NEW BRUNSWICK,NJ 08903. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. OI Reed, Danielle/0000-0002-4374-6107 FU NIDDK NIH HHS [1-F32DK08732-01, R01-DK-44073, R01-DK-48095] NR 25 TC 156 Z9 160 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 1996 VL 45 IS 5 BP 691 EP 694 DI 10.2337/diabetes.45.5.691 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UJ231 UT WOS:A1996UJ23100026 PM 8621025 ER PT J AU Schmidt, MI Duncan, BB Watson, RL Sharrett, AR Brancati, FL Heiss, G AF Schmidt, MI Duncan, BB Watson, RL Sharrett, AR Brancati, FL Heiss, G TI A metabolic syndrome in whites and African-Americans - The atherosclerosis risk in communities baseline study SO DIABETES CARE LA English DT Article ID INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; BLOOD-PRESSURE; SYNDROME-X; HYPERTENSION AB OBJECTIVE - To describe clustering of hypertriglyceridemia, low HDL cholesterol, hypertension, diabetes, and hyperuricemia and its association with fasting insulin, waist-to-hip ratio (WHR), and BMI for African-American and white men and women. RESEARCH DESIGN AND METHODS - Observed frequencies of clusters were compared with those expected in 14,481 participants, 45-64 years of age, of the Atherosclerosis Risk in Communities (ARIC) baseline sun ey, 1987-1989. Associations of clusters with insulin, central adiposity, and overall obesity, as well as with individual abnormalities, were analyzed through multiple logistic regression. RESULTS - Clustering beyond chance was observed in all four sex/ethnic groups (P < 0.001), with 7% of the sample presenting 30% of the abnormalities in large clusters (greater than or equal to 3 abnormalities per individual!. The odds ratio (OR) for the association of each abnormality with clustering of the remaining four ranged from 1.6 to 8.8 (P < 0.01). These odds of clustering were notably large in white women. Of the abnormalities, hypertriglyceridemia demonstrated the highest OR (5.0-8.8) and diabetes had a lower OR in African-American subjects than in white subjects (P < 0.001). Insulin, WHR, and BMI were statistically associated with clustering in all groups (P < 0.001, except for BMI in African-Americans). CONCLUSIONS - Clustering of abnormalities consistent with the concept of a metabolic syndrome is present in both white and African-American subjects. C1 UNIV FED RIO GRANDE SUL,SCH MED,DEPT SOCIAL MED,PORTO ALEGRE,RS,BRAZIL. UNIV MISSISSIPPI,MED CTR,DEPT PREVENT MED,DIV EPIDEMIOL,JACKSON,MS 39216. NHLBI,BETHESDA,MD 20892. JOHNS HOPKINS MED INST,WELCH CTR PREVENT EPIDEMIOL & CLIN RES,BALTIMORE,MD 21205. UNIV N CAROLINA,SCH PUBL HLTH,DEPT EPIDEMIOL,CHAPEL HILL,NC 27514. NR 24 TC 102 Z9 104 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 1996 VL 19 IS 5 BP 414 EP 418 DI 10.2337/diacare.19.5.414 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UJ651 UT WOS:A1996UJ65100002 PM 8732701 ER PT J AU Johnson, EO vandenBree, MBM Uhl, GR Pickens, RW AF Johnson, EO vandenBree, MBM Uhl, GR Pickens, RW TI Indicators of genetic and environmental influences in drug abusing individuals SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE genetics; twins; drug dependence; males ID ALCOHOLISM; INHERITANCE; POPULATION; TWIN AB To assess relative contribution of genetic and environmental influences in individual cases of drug abuse/dependence, separate scales were constructed from DIS (Version III) drug symptom items. Using data from 38 MZ and 35 DZ male twin pairs, items with significant MZ/DZ differences in probandwise concordance were assigned to a genetic scale whereas items without significant MZ/DZ differences were assigned to an environmental scale. As expected, significant differences were found between MZ and DZ twins in intraclass correlations for the genetic but not environmental scale. Genetic scores on drug and alcohol scales were correlated (r = 0.40), whereas environmental scores were not. When scores on the genetic scales were compared, the correlation between drug and alcohol scores within individuals was similar to that across MZ twins, both of which were higher than the correlation across DZ twins. These results suggest (1) relative contribution of genetic and environmental influences in individual cases of drug dependence can be assessed, and (2) common genetic mechanisms may be involved in alcohol and drug dependence. RP Johnson, EO (reprint author), NIDA,CLIN NEUROGENET SECT,DIV INTRAMURAL RES,POB 5180,BALTIMORE,MD 21224, USA. RI turton, miranda/F-4682-2011 NR 29 TC 13 Z9 13 U1 1 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAY PY 1996 VL 41 IS 1 BP 17 EP 23 DI 10.1016/0376-8716(96)01223-9 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA UR326 UT WOS:A1996UR32600003 PM 8793306 ER PT J AU Baumann, MH Schuster, CR Rothman, RB AF Baumann, MH Schuster, CR Rothman, RB TI Effects of phentermine and cocaine on fenfluramine-induced depletion of serotonin in mouse brain SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE phentermine; fenfluramine; cocaine; serotonin; rats ID RAT-BRAIN AB The combined administration of phentermine and fenfluramine (PHEN/FEN) has been used as a treatment for obesity. Recent evidence suggests that this drug mixture may also be an effective medication for substance abuse disorders, including cocaine dependence. It is well-established that repeated high-dose fenfluramine causes serotonin (5-HT) terminal degeneration in laboratory animals, and no studies have addressed possible interactions between phentermine and fenfluramine. The purpose of the present work was to examine the effect of phentermine coadministration on fenfluramine-induced depletion of 5-HT in mouse forebrain. In addition, because of the potential for cocaine abuse in drug addicts taking PHEN/FEN as a medication, we examined the effects of PHEN/FEN on forebrain 5-HT levels in the presence or absence of cocaine. Fenfluramine (0, 3, 10, 30 mg/kg, s.c. twice daily for 4 days) caused a dose-dependent reduction in forebrain 5-HT without affecting dopamine or norepinephrine. Phentermine coadministration (7 mg/kg, s.c. twice daily for 4 days) did not significantly alter the 5-HT-depleting effect of fenfluramine. Likewise, cocaine (10 mg/kg, i.p.), administered 60 min prior to or 60 min after PHEN/FEN, had no effect on the PHEN/FEN-induced decrease in central 5-HT. The present results indicate that doses of phentermine far above those typically administered to humans do not potentiate the 5-HT-depleting effect of repeated high-dose fenfluramine. Moreover, exposure to cocaine does not significantly alter the long-term neurochemical actions of the PHEN/FEN mixture. C1 WAYNE STATE UNIV,SCH MED,DEPT PSYCHIAT & BEHAV NEUROSCI,DETROIT,MI 48207. RP Baumann, MH (reprint author), NIDA,CLIN PSYCHOPHARMACOL SECT,NIH,DIV INTRAMURAL RES,4940 EASTERN AVE,BLDG C,BALTIMORE,MD 21224, USA. NR 15 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAY PY 1996 VL 41 IS 1 BP 71 EP 74 DI 10.1016/0376-8716(96)01234-3 PG 4 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA UR326 UT WOS:A1996UR32600009 PM 8793312 ER PT J AU Mathews, JM Black, SL Matthews, HB AF Mathews, JM Black, SL Matthews, HB TI P,P'-dichlorodiphenyl sulfone metabolism and disposition in rats SO DRUG METABOLISM AND DISPOSITION LA English DT Article AB p,p'-Dichlorodiphenyl sulfone (DDS) is a lipophilic monomer used extensively in the synthesis of high temperature plastics. Studies of the fate of uniformly labeled [C-14]DDS in the rat have established that it is readily absorbed from the gastrointestinal tract, distributed to all tissues examined, and concentrated in adipose tissue, After intravenous administration of 10 mg/kg and determination of the time course of DDS distribution, increasing accumulation of DDS in adipose was observed up to 24 hr, followed by slow elimination with a half-life of similar to 12 days. DDS equivalents in tissues were primarily (>90%) parent compound, whereas excreted DDS equivalents were primarily (>80%) present as metabolites. On repeat oral dosing at 10 mg/kg, levels of DDS in tissues seemed to reach steady state after similar to 2 weeks, at which time the concentrations in adipose reached 265 mu g/g tissue, Hepatic cytochrome P450 (CYP) content, ethoxyresorufin O-deethylase activities, and levels of metabolites arising from phase I metabolism were doubled after repeat oral administration of DDS, but benzphetamine N-demethylase activity was unchanged, Thus, it seems that DDS induces CYP1A forms, but not CYP2B isozymes. DDS-derived radioactivity was excreted primarily in feces and to a lesser extent in urine as a phenolic metabolite and its glucuronide, The aglycone of this glucuronide was isolated and characterized by NMR and MS as 3-hydroxy-4,4'-dichlorodiphenyl sulfone. C1 NATL INST ENVIRONM HLTH SCI,RES TRIANGLE PK,NC. RP Mathews, JM (reprint author), RES TRIANGLE INST,CTR BIOORGAN CHEM,POB 12194,3040 CORNWALLIS RD,RES TRIANGLE PK,NC 27709, USA. FU NIEHS NIH HHS [N01-ES-15329] NR 8 TC 6 Z9 6 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD MAY PY 1996 VL 24 IS 5 BP 579 EP 587 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UJ234 UT WOS:A1996UJ23400015 PM 8723740 ER PT J AU Avantaggiati, ML Carbone, M Graessmann, A Nakatani, Y Howard, B Levine, AS AF Avantaggiati, ML Carbone, M Graessmann, A Nakatani, Y Howard, B Levine, AS TI The SV40 large T antigen and adenovirus E1a oncoproteins interact with distinct isoforms of the transcriptional co-activator, p300 SO EMBO JOURNAL LA English DT Article DE E1a; p300; revertant; Tag; transformation; ubiquitination ID MULTIUBIQUITIN CHAIN; CELL-TRANSFORMATION; GROWTH-CONTROL; PROTEINS; GENE; PRODUCT; PHOSPHORYLATION; DEGRADATION; BINDING; POLYOMAVIRUS AB p300 is a nuclear phosphoprotein likely to be involved in the control of cell growth. Here we show that SV40 large T antigen (Tag) forms a specific complex with p300. In various Tag-expressing cell lines, the affinity of Tag for p300 was restricted to a newly identified unphosphorylated but ubiquitinated form of the protein. Further, Tag did not associate with p300 in an SV40 Tag-producing cell line (REV2) in which the original transformed phenotype (SV52) is reverted. Biochemical studies demonstrate that both the phosphorylation and the ubiquitination profile of p300 are altered in REV2 with respect to the wild-type fully transformed SV52 parental cells, wherein Tag-p300 complexes are readily detected. In contrast to Tag, the adenovirus early expression product E1a interacts with both phosphorylated and unphosphorylated forms of p300. In addition, when REV2 cells were infected with adenovirus, E1a-p300 complexes were detected, suggesting that the p300 expressed in REV2 has lost the affinity for Tag, but not for E1a. We then compared the ability of Tag and E1a to affect the transcription levels of the cAMP-responsive promoter (CRE), which is modulated in vivo by p300, in REV2 cells. We found that Tag repressed the CRE promoter in all of the cell lines in which Tag-p300 complexes were detected, but not in REV2 cells. In contrast, E1a efficiently inhibited CRE-directed transcription in this cell line. The data thus indicate that the different specificities exhibited by Tag and E1a towards the various forms of p300 are reflected in vivo as a difference in the ability of these viral oncoproteins to modulate the expression of CRE-containing genes. C1 NICHHD,SECT DNA REPLICAT REPAIR & MUTAGENESIS,BETHESDA,MD 20892. NICHHD,LAB MOLEC GROWTH REGULAT,BETHESDA,MD 20892. UNIV CHICAGO,DEPT PATHOL,CHICAGO,IL 60637. FREE UNIV BERLIN,INST MOLEK BIOL & BIOCHEM,BERLIN 33,GERMANY. NR 36 TC 137 Z9 138 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 1 PY 1996 VL 15 IS 9 BP 2236 EP 2248 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UK074 UT WOS:A1996UK07400021 PM 8641289 ER PT J AU Baggio, MC MedeirosNeto, G Osawa, Y Nguyen, NY Santisteban, P Knobel, M Grollman, EF AF Baggio, MC MedeirosNeto, G Osawa, Y Nguyen, NY Santisteban, P Knobel, M Grollman, EF TI Amino acid composition of proteins extracted from endemic goiter glands SO ENDOCRINE PATHOLOGY LA English DT Article DE thyroid albumin; iodine-deficiency goiter; thyroglobulin; endemic goiter; amino acid composition ID CONGENITAL GOITER; THYROID PEROXIDASE; FAMILIAL GOITER; THYROGLOBULIN; ALBUMIN AB Proteins were isolated and characterized in thyroid tissue of six patients from Brazil with endemic goiter. Biochemical studies of these thyroidal proteins included gel filtration, electrophoresis, and amino acid analysis. In addition to thyroglobulin, two of the most abundant proteins found in all goiters studied had molecular weights of 68 and 14 kDa, One protein was identified as albumin based on its immunoreactivity with antibodies to serum albumin. The other protein was identified as a hemoglobin subunit using reverse-phase high-performance liquid chromatography (HPLC). Identification was confirmed by partial N-terminal amino acid sequencing that showed several nonconservative differences in thyroid albumin when compared to human serum albumin (HSA). Biochemical findings were correlated with iodine and hormone contents in serum and thyroglobulin from these patients. Based on these findings, we suggest that hemoglobin and albumin are taken up from the blood by the hyperplastic thyroid tissue, Albumin would be processed by the thyroid follicular cell, becoming iodinated and released into the circulation. C1 UNIV SAO PAULO,HOSP CLIN,SCH MED,DIV ENDOCRINOL,THYROID UNIT,BR-01065970 SAO PAULO,BRAZIL. NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892. NHLBI,NIH,MOLEC IMMUNOL LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,FACIL BIOTECHNOL RESOURCES,BETHESDA,MD. RI Santisteban, Pilar/E-7829-2016 OI Santisteban, Pilar/0000-0002-2758-796X NR 24 TC 3 Z9 3 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 1046-3976 J9 ENDOCR PATHOL JI Endocr. Pathol. PD MAY PY 1996 VL 7 IS 2 BP 137 EP 143 DI 10.1007/BF02739973 PG 7 WC Endocrinology & Metabolism; Pathology SC Endocrinology & Metabolism; Pathology GA UN720 UT WOS:A1996UN72000005 ER PT J AU Yoshikawa, T Makino, S Gao, XM Xing, GQ Chuang, DM DeteraWadleigh, SD AF Yoshikawa, T Makino, S Gao, XM Xing, GQ Chuang, DM DeteraWadleigh, SD TI Splice variants of rat TR4 orphan receptor: Differential expression of novel sequences in the 5'-untranslated region and C-terminal domain SO ENDOCRINOLOGY LA English DT Article ID CEREBELLAR GRANULE CELLS; MESSENGER-RNA EXPRESSION; SITE SELECTION; RETINOIC ACID; GENE; GLUTAMATE; BRAIN; SUPERFAMILY; INDUCTION; ISOFORMS AB The use of rapid amplification of 5'-cDNA ends-PCR yielded two novel sequences for the rat orphan receptor, TR4, representing heterogeneity on the 5'-untranslated region. Genomic structure analysis revealed that the 5'-untranslated region of the longer messenger RNA fragment, rTR4-1, contained three exons, (alpha, beta, and gamma. The skipping of exon gamma gave rise to rTR4-2, indicating that rTR4-1 and rTR4-2 are products of alternative splicing. We isolated another novel rat TR4 splice variant, rTR4-NS, which was found to diverge from rTR4-2 at codon 504. rTR4-NS contained an unspliced intronic sequence with in-frame codons for eight amino acids followed by a termination codon. The three TR4 messenger RNA variants were differentially expressed. rTR4-NS appeared to be a rare transcript found in limited areas of the brain. In situ hybridization detected prominent TR4 signals in brain areas known to be involved in stress response. In cerebellar granule cells, the rise in TR4 expression correlated with the progression of neuronal maturation. N-Methyl-D-aspartate treatment triggered a marked increase in TR4 expression. These results suggest a possible role for TR4 in neuronal differentiation. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. NIMH,MOLEC PHARMACOL SECT,BIOL PSYCHIAT BRANCH,NIH,BETHESDA,MD 20892. RP Yoshikawa, T (reprint author), NIMH,UNIT GENE MAPPING & EXPRESS,CLIN NEUROGENET BRANCH,NIH,BLDG 10,ROOM 3N218,BETHESDA,MD 20892, USA. NR 47 TC 11 Z9 11 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 1996 VL 137 IS 5 BP 1562 EP 1571 DI 10.1210/en.137.5.1562 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UG636 UT WOS:A1996UG63600009 PM 8612486 ER PT J AU IgnarTrowbridge, DM Pimentel, M Parker, MG McLachlan, JA Korach, KS AF IgnarTrowbridge, DM Pimentel, M Parker, MG McLachlan, JA Korach, KS TI Peptide growth factor cross-talk with the estrogen receptor requires the A/B domain and occurs independently of protein kinase C or estradiol SO ENDOCRINOLOGY LA English DT Article ID BREAST-CANCER-CELLS; FACTOR-I; TRANSCRIPTIONAL ACTIVATION; MEDIATED TRANSCRIPTION; PROGESTERONE-RECEPTOR; MCF-7 CELLS; GENE-EXPRESSION; PHOSPHORYLATION; INSULIN; BINDING AB Modulation of steroid receptor-dependent transcription by extracellular ligands represents a novel mechanism of steroid receptor regulation. We have assessed the effects of epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha), and insulin-like growth factor I (IGF-I) on transcription from consensus estrogen response elements (ERE) in estrogen receptor (ER)-positive BG-1 human ovarian adenocarcinoma cells. EGF, TGF alpha, IGF-I, and estradiol (E(2)) enhanced transcription in a dose-dependent manner using either a strong or a minimal promoter, and ICI 164,384, a specific ER antagonist, inhibited these responses. Combinations of E(2) with TGF alpha or IGF-I induced synergistic activation of transcription from an ERE, whereas an additive response was observed with combinations of IGF-I and TGF alpha or EGF. Tetradecanoyl 12-phorbol 13-acetate (TPA), a protein kinase C (PKC) activator, stimulated ERE-mediated transcription, and this effect was inhibited by ICI 164,384. Bisindolyl-maleimide, a relatively specific inhibitor of PKC, completely antagonized TPA-induced transcription, but did not affect the response to TGF alpha, IGF-I, or E(2). The combination of TPA with E(2) in transcriptional synergism was inhibited by ICI 164,384; conversely, the combination of TPA with either TGF alpha or IGF-I elicited a response only equal to the maximal TPA response. Thus, peptide growth factors elicit ER-dependent transcription independently of PKC; however, there may be a common mechanistic component, as saturation of response was observed. Finally, activation of ERE-dependent transcription in Chinese hamster ovary cells by IGF-I was observed in the presence of a mutant receptor that lacks estrogen-binding activity. The effects of both IGF-I and E(2) were dependent on the ability of the ER to bind to DNA. IGF-I elicited only weak transcriptional activation in the presence of a deletion mutant that lacked the entire A/B domain; however, synergism between IGF-I and E(2) was observed with this mutant. Therefore, ligand-independent activation of ER-dependent transcription by IGF-I is predominantly mediated through activation function I by a mechanism distinct from that of E(2). C1 NIEHS, REPROD & DEV TOXICOL LAB, NIH, RES TRIANGLE PK, NC 27709 USA. IMPERIAL CANC RES FUND, MOLEC ENDOCRINOL LAB, LONDON WC2A 3PX, ENGLAND. OI Korach, Kenneth/0000-0002-7765-418X NR 54 TC 180 Z9 183 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 1996 VL 137 IS 5 BP 1735 EP 1744 DI 10.1210/en.137.5.1735 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UG636 UT WOS:A1996UG63600032 PM 8612509 ER PT J AU DeLeon, DD Terry, C Asmerom, Y Nissley, P AF DeLeon, DD Terry, C Asmerom, Y Nissley, P TI Insulin-like growth factor II modulates the routing of cathepsin D in MCF-7 breast cancer cells SO ENDOCRINOLOGY LA English DT Article ID MANNOSE 6-PHOSPHATE RECEPTOR; IGF-II; MANNOSE-6-PHOSPHATE RECEPTOR; BETA-GALACTOSIDASE; LYSOSOMAL-ENZYMES; CELLULAR UPTAKE; BINDING; EXPRESSION; OVEREXPRESSION; RAT AB A previous observation that insulin-like growth factor II (IGF-II) inhibits the cellular uptake of a lysosomal enzyme by inhibiting binding to the IGF-II/mannose 6-phosphate receptor led to the proposal that, in a cell producing IGF-II, the routing of lysosomal enzymes might be altered. To test this hypothesis MCF-7 breast cancer cells were transfected with pRc/CMV vector only (CMV) or vector containing IGF-II complementary DNA encoding either mature (M-II) or precursor (P-II) IGF-II, and the routing of cathepsin D, a predominant lysosomal enzyme in this cell line, was examined. The concentration of IGF-II in media conditioned by P-II clones (11.2 +/- 4.3 mu g/ml) was much higher than in media conditioned by M-II clones (1.3 +/- 1.5 mu g/ml). Metabolic labeling experiments were performed with 10 mM mannose 6-phosphate present in the medium to block reuptake of lysosomal enzymes. Cell extracts (C) and media (M) were immuno-precipitated with a cathepsin D antiserum, and immunoprecipitates were analyzed by SDS-PAGE. The mean of the C/M ratio of cathepsin D for the seven P-II clones (1.60 +/- 0.13) was significantly lower than for the six CMV clones (3.47 +/- 0.48). Similar results were obtained when conditioned M and C were examined by immunoblotting after a 48-h incubation. The mean of the C/M ratio for the seven P-II clones (11.4 +/- 1.6) was significantly lower than for the six CMV clones (24.9 +/- 5.2). There was also a strong negative correlation between the ratio of intracellular cathepsin D to extracellular cathepsin D and relative cathepsin D synthesis (r = 0.843), consistent with increased cathepsin D production in cells overexpressing IGF-II. It is concluded that endogenous IGF-II modulates the routing of cathepsin D in MCF-7 cells. C1 NCI,NIH,BETHESDA,MD 20892. LOMA LINDA UNIV,SCH MED,LOMA LINDA,CA 92350. OI De Leon, Daisy D./0000-0002-2693-0957 NR 44 TC 25 Z9 25 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 1996 VL 137 IS 5 BP 1851 EP 1859 DI 10.1210/en.137.5.1851 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UG636 UT WOS:A1996UG63600047 PM 8612524 ER PT J AU Lee, CY Rechler, MM AF Lee, CY Rechler, MM TI Proteolysis of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in 150-kilodalton IGFBP complexes by a cation-dependent protease activity in adult rat serum promotes the release of bound IGF-I SO ENDOCRINOLOGY LA English DT Article ID FACTOR-BINDING-PROTEINS; PREGNANCY; SUBUNIT; HORMONE AB Insulin-like growth factor I (IGF-I) circulates in plasma predominantly in a 150-kDa complex together with IGF-binding protein-3 (IGFBP-3), an approximately 40-kDa glycoprotein that binds IGF-I with high affinity, and an 85-kDa acid-labile subunit that does not bind IGFs. The 150-kDa complex serves as a potential reservoir of IGF-I by sequestering the growth factor in the vascular compartment. Before IGF-I can reach the tissues, however, it must be released from the complex in a form that can cross the capillary-endothelial barrier. The present study demonstrates that proteolysis of IGFBP-3 in the 150-kDa complex occurs in vitro and results in the release of IGF-I. Specific IGFBP-3 protease activity in adult rat serum was demonstrated by incubating the serum at 37 C in the presence and absence of various protease inhibitors, followed by ligand blotting. Intact and truncated (30-kDa) IGFBP-3 were almost completely proteolyzed after 12 h of incubation, whereas IGFBP-2 and IGFBP-4 in the serum were unchanged even after 48-h incubation. The IGFBP-3 protease activity was inhibited by EDTA, indicating cation dependence, and by 4-(2-aminoethyl)-benzenesulfonyl fluoride, a serine protease inhibitor. Fractionation of the serum after incubation indicated that IGFBP-3 was proteolyzed while it was part of the 150-kDa complex. Proteolysis of human IGFBP-3 (hIGFBP-3) also occurred within 150-kDa complexes when ternary complexes that had been reconstituted from recombinant hIGFBP-3, rat acid-labile subunit, and IGF-I were incubated with rat serum. Release of IGF-I from ternary complexes after proteolysis of hIGFBP-3 was indicated by the observation that some of the [I-125]IGF-I initially associated with reconstituted 150-kDa complexes was transferred to endogenous rat IGFBPs during the incubation. Similar proteolysis of IGFBP-3 within 180-kDa complexes in vivo would provide a mechanism for mobilizing IGF-I from the circulating reservoir in plasma as well as for the turnover of IGFBP-3. RP Lee, CY (reprint author), NIDDKD, GROWTH & DEV SECT, MOLEC & CELLULAR ENDOCRINOL BRANCH,NIH,BLDG 10, ROOM 8D14, 10 CTR DR, BETHESDA, MD 20892 USA. NR 20 TC 37 Z9 38 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 1996 VL 137 IS 5 BP 2051 EP 2058 DI 10.1210/en.137.5.2051 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UG636 UT WOS:A1996UG63600070 PM 8612547 ER PT J AU Migliaccio, S Newbold, RR Bullock, BC Jefferson, WJ Sutton, FG McLachlan, JA Korach, KS AF Migliaccio, S Newbold, RR Bullock, BC Jefferson, WJ Sutton, FG McLachlan, JA Korach, KS TI Alterations of maternal estrogen levels during gestation affect the skeleton of female offspring SO ENDOCRINOLOGY LA English DT Article ID OSTEOBLAST-LIKE CELLS; BONE-MINERAL DENSITY; POSTMENOPAUSAL OSTEOPOROSIS; PRENATAL EXPOSURE; SEX STEROIDS; RECEPTOR; MOUSE; MICE; RATS; 17-BETA-ESTRADIOL AB Estrogens have important effects on bone turnover in both humans and experimental animal models. Moreover, the decreased level of estrogens after menopause appears to be one of the key factors in determining postmenopausal osteoporosis. The presence of estrogen receptor in both osteoblasts and osteoclasts has suggested a direct role of these steroid hormones on bone tissue. Thus, this tissue is now regarded as a specific estrogen target tissue. Exposure to estrogens during various stages of development has been shown to irreversibly influence responsive target organs. We have recently shown that transient developmental neonatal exposure (days 1-5 of life) of female mice to estrogen resulted in an augmented bone density in the adult animals. The aim of the present study was to evaluate whether shortterm modification of maternal estrogen levels during pregnancy would induce changes in the skeleton of the developing fetuses and to identify any long-term alterations that may occur. Pregnant mice were injected with varying doses (0.1-100 mu g/kg maternal BW) of the synthetic estrogen diethylstilbestrol (DES) from day 9-16 of pregnancy. Offspring were weaned at 21 days of age, and effects on bone tissue of the female mice were evaluated in adulthood (6-9 months of age). Prenatal DES treatment(s) did not significantly affect BW. However, a dose-dependent increase in bone mass, both in the trabecular and cortical compartments, was observed in the prenatal DES-exposed female offspring. Furthermore, long bones of DES-exposed females were shorter than controls. Normal skeletal mineralization accompanied these changes in the bone tissue, as shown by a parallel increase in skeletal calcium content. Double tetracycline labeling performed in 6-month-old DES-exposed animals showed increase in mineral apposition rate in adult DES-exposed mice as compared with untreated control animals, although no significant difference in the circulating estrogen levels was found in animals of this age. Experiments were then performed to evaluate whether perturbation of the estrogen surge at puberty in these diethylstilbestrol (DES)-exposed mice could reverse the observed changes. Femur length was chosen as a marker of potential estrogenic effect. Prepubertal ovariectomy of the prenatally DES-treated animals could only partially reverse the effects observed in the skeleton of the DES-treated animals. Further experiments were performed to evaluate whether these changes could have occurred in utero. CD-1 pregnant female mice were injected with DES (100 mu g/kg maternal BW) from days 9-15 of gestation. On day 16 of gestation, fetuses were examined and stained by a standard Alizarin Red S and Alcian Blue procedure to visualize calcified and uncalcified skeletal tissue. Estrogen treatment induced an increase in the amount of calcified skeleton as compared with untreated controls and also a decrease in the length of long bones, strongly suggesting a change in both endochondral ossification and endosteal and periosteal bone formation. In summary, these data show, for the first time, that alterations in the maternal estrogenic levels during pregnancy can influence early phases of fetal bone tissue development and subsequently result in permanent changes in the skeleton. Finally, the effect of this short-term estrogen treatment can be seen in the fetal skeleton, suggesting an estrogen-imprinting effect on bone cell-programming in fetal life because treatment effects on bone cell turnover can be observed later in adult life. C1 NIEHS,REPROD & DEV TOXICOL LAB,RECEPTOR BIOL SECT,RES TRIANGLE PK,NC 27709. NIEHS,ENVIRONM TOXICOL PROGRAM,TOXICOL BRANCH,REPROD TOXICOL GRP,DEV ENDOCRINOL SECT,RES TRIANGLE PK,NC 27709. UNIV ROMA LA SAPIENZA,DEPT EXPTL MED,I-00191 ROME,ITALY. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT COMPARAT MED,WINSTON SALEM,NC 27109. TULANE UNIV,DEPT PHARMACOL,CTR BIOENVIRONM RES,NEW ORLEANS,LA 70112. OI Migliaccio, Silvia/0000-0002-4563-6630; Korach, Kenneth/0000-0002-7765-418X NR 55 TC 50 Z9 51 U1 0 U2 5 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 1996 VL 137 IS 5 BP 2118 EP 2125 DI 10.1210/en.137.5.2118 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UG636 UT WOS:A1996UG63600079 PM 8612556 ER PT J AU Harris, CC AF Harris, CC TI p53 tumor suppressor gene: At the crossroads of molecular carcinogenesis, molecular epidemiology, and cancer risk assessment SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT 2nd International Conference on Environmental Mutagens in Human Populations CY AUG 20-25, 1995 CL PRAGUE, CZECH REPUBLIC SP Prague Inst Adv Studies, Prague, Czech Republic, Reg Inst Hygiene Cent Bohemia, Prague, Czech Republic, Univ Tex Med Branch DE p53 gene; molecular carcinogenesis; molecular epidemiology; cancer risk assessment ID CELL-CYCLE CHECKPOINT; WILD-TYPE P53; DNA-REPAIR; NITRIC-OXIDE; MUTATIONS; TRANSCRIPTION; AMPLIFICATION; FIBROBLASTS; CARCINOMA; APOPTOSIS AB Carcinogenesis is a multistage process involving the inappropriate activation of normal cellular genes to become oncogenes, e.g., ras, and the inactivation of other cellular genes called tumor suppressor genes. p53 is the prototypic tumor suppressor gene that is well suited as a molecular link between the causes of cancer, i.e., carcinogenic chemical and physical agents and certain viruses, and the development of clinical cancer. The p53 tumor suppressor gene is mutated in the majority of human cancers. Genetic analysis of human cancer is providing clues to the etiology of these diverse tumors and to the functions of the p53 gene. Some of the mutations in the p53 gene reflect endogenous causes of cancer, whereas others are characteristic of carcinogens found in our environment. In geographic areas where hepatitis B virus and a dietary chemical carcinogen, aflatoxin B-1, are risk factors of liver cancer, a molecular signature of the chemical carcinogen is found in the mutated p53 gene. A different molecular signature in the p53 gene is found in skin cancer caused by sunlight. Because mutations in the p53 gene can occur in precancerous lesions in the lung, breast, esophagus, and colon, molecular analysis of the p53 gene in exfoliated cells found in either body fluids or tissue biopsies may identify individuals at increased cancer risk. p53 mutations in tumors generally indicate a poorer prognosis. In summary, the recent history of p53 investigations is a paradigm in cancer research, illustrating both the convergence of previously parallel lines of basic, clinical, and epidemiologic investigation and the rapid translation of research findings from the laboratory to the clinic. RP Harris, CC (reprint author), NCI,HUMAN CARCINOGENESIS LAB,NIH,BLDG 37,RM 2C01,BETHESDA,MD 20892, USA. NR 43 TC 80 Z9 85 U1 1 U2 1 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 1996 VL 104 SU 3 BP 435 EP 439 DI 10.2307/3432799 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA UQ084 UT WOS:A1996UQ08400005 PM 8781359 ER PT J AU Olden, K AF Olden, K TI A bad start for socioeconomically disadvantaged children SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material RP Olden, K (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 1996 VL 104 IS 5 BP 462 EP 463 DI 10.2307/3432978 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA UP689 UT WOS:A1996UP68900001 PM 8743427 ER PT J AU Suk, WA Collman, G Damstra, T AF Suk, WA Collman, G Damstra, T TI Human biomonitoring: Research goals and needs SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT 2nd International Conference on Environmental Mutagens in Human Populations CY AUG 20-25, 1995 CL PRAGUE, CZECH REPUBLIC SP Prague Inst Adv Studies, Prague, Czech Republic, Reg Inst Hygiene Cent Bohemia, Prague, Czech Republic, Univ Tex Med Branch DE biomonitoring; biomarkers; molecular epidemiology; human population studies; exposure assessment; environmental health ID EXPOSURE; CANCER; RISK AB Epidemiological studies have taken advantage of a number of strategies to monitor human populations for mortality, incidence, and exposure to hazardous environmental agents. These studies have been compromised by the lack of individual exposure assessment data that precisely quantifies internal dose. As methods improve in analytical chemistry and molecular biology, direct biological monitoring of exposed populations is possible. Biomarkers have been developed and validated in exposed populations that quantify individual exposure, susceptibility, and early markers of health effects and can be used to study relationships between exposures and environmentally induced diseases. This paper provides background on the state of the art of human populations monitoring and, through a series of case studies, provides examples of novel biomarkers of exposure, susceptibility, and effect that highlight new opportunities for biomonitoring. Prevention of human disease due to environmental contaminants can be accomplished by implementing strategies such as those discussed to monitor exposures and early health effects in human populations. RP Suk, WA (reprint author), NIEHS, DIV EXTRAMURAL RES & TRAINING, POB 12233, 104 ALEXANDER DR, RES TRIANGLE PK, NC 27709 USA. NR 28 TC 12 Z9 14 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 1996 VL 104 SU 3 BP 479 EP 483 DI 10.2307/3432808 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA UQ084 UT WOS:A1996UQ08400014 PM 8781368 ER PT J AU Cunningham, ML Hayward, JJ Shane, BS Tindall, KR AF Cunningham, ML Hayward, JJ Shane, BS Tindall, KR TI Distinction of mutagenic carcinogens from a mutagenic noncarcinogen in the Big Blue transgenic mouse SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT 2nd International Conference on Environmental Mutagens in Human Populations CY AUG 20-25, 1995 CL PRAGUE, CZECH REPUBLIC SP Prague Inst Adv Studies, Prague, Czech Republic, Reg Inst Hygiene Cent Bohemia, Prague, Czech Republic, Univ Tex Med Branch DE diaminotoluene; in vivo mutation assay; dimethylnitrosamine; mutagenic noncarcinogens; Big Blue; transgenic mice; lacI ID MICE; 2,6-DIAMINOTOLUENE; MUTATIONS; DNA AB The aromatic amines 2,4-diaminotoluene (2,4-DAT) and 2,6-diaminotoluene (2,6-DAT) are structural isomers that have been extensively studied for their mutagenic and carcinogenic characteristics. Both compounds are rapidly absorbed alter oral administration and are equally mutagenic in the Ames test; however 2,4-DAT is a potent hepatocarcinogen, whereas 2,6-DAT does not produce an increased incidence of rumors in rats or mice at similar doses. The Big Blue transgenic B6C3F(1) mouse carries multiple copies of the lacl mutational target gene. Our studies were designed to determine whether the Big Blue system could be used to detect differences in the in vivo mutagenic activity between the carcinogen-noncarcinogen pair 2,4-DAT and 2,6-DAT and to determine whether the in vivo mutagenesis assay results correspond to the rodent carcinogen bioassay results. Male B6C3F(1) transgenic mice were exposed to 2,4-DAT or 2,6-DAT at 0 or 1,000 ppm in the diet for 30 and 90 days or to dimethylnitrosamine as a positive control. Mutant frequencies were nearly identical for all three groups at: 30 days, while at 90 days the mutant frequency for the hepatocarcinogen 2,4-DAT (12.1 +/- 1.4 x 10(-5)) was significantly higher (p < 0.01) as compared to both age-matched (spontaneous) controls (5.7 +/- 2.9 x 10(-5)) and the 2,6-DAT-exposed group (5.7 +/- 2.4 x 10(-5)). Results from this study demonstrate that the Big Blue transgenic mutation assay can distinguish differences in vivo between the mutagenic responses of hepatic carcinogens and a noncarcinogen; is sensitive to mutagens through subchronic dietary exposure; and yields a differential response depending upon the length of lime mice are exposed to a mutagen. C1 NIEHS,ENVIRONM CARCINOGENESIS PROGRAM,RES TRIANGLE PK,NC 27709. LOUISIANA STATE UNIV,INST ENVIRONM STUDIES,BATON ROUGE,LA 70803. RP Cunningham, ML (reprint author), NIEHS,CHEM BRANCH,ENVIRONM TOXICOL PROGRAM,POB 12233,MD B3-10,RES TRIANGLE PK,NC 27709, USA. NR 19 TC 11 Z9 11 U1 0 U2 1 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 1996 VL 104 SU 3 BP 683 EP 686 DI 10.2307/3432845 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA UQ084 UT WOS:A1996UQ08400051 PM 8781405 ER PT J AU Rinaldo, A Marchiori, C Faggionato, L Saffiotti, U Ferlito, A AF Rinaldo, A Marchiori, C Faggionato, L Saffiotti, U Ferlito, A TI The association of cancers of the larynx with cancers of the lung SO EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY LA English DT Article DE respiratory tract malignancy; primary laryngeal cancer; primary lung cancer; synchronous neoplasms; metachronous neoplasms ID NECK-CANCER; CARCINOMA; HEAD AB We report 77 cases of associated primary cancers of the larynx and lung that were managed at the Department of Otolaryngology, University of Padua, between 1980 and 1994. To our knowledge, this is the largest series reported in the literature to date. This association is not a chance finding, but presumably the result of common pathogenetic factors. C1 UNIV PADUA,NUOVO POLICLIN,DEPT OTOLARYNGOL,I-35128 PADUA,ITALY. NCI,DIV BASIC SCI,LAB EXPT PATHOL,BETHESDA,MD 20892. NR 23 TC 6 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0937-4477 J9 EUR ARCH OTO-RHINO-L JI Eur. Arch. Oto-Rhino-Laryn. PD MAY PY 1996 VL 253 IS 4-5 BP 256 EP 259 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA UQ981 UT WOS:A1996UQ98100012 PM 8737780 ER PT J AU Whitcup, SM Rizzo, LV Lai, JC Hayashi, S Gazzinelli, R Chan, CC AF Whitcup, SM Rizzo, LV Lai, JC Hayashi, S Gazzinelli, R Chan, CC TI IL-12 inhibits endotoxin-induced inflammation in the eye SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE interleukin-12; endotoxin; eye; inflammation; cytokine ID TUMOR-NECROSIS-FACTOR; INDUCED UVEITIS; INTERFERON-GAMMA; IFN-GAMMA; RAT; INTERLEUKIN-1; LYMPHOCYTES; INDUCTION; CYTOKINE; CELLS AB Interleukin-12 (IL-12) is a heterodimeric cytokine that induces interferon (IFN)-gamma production and an increased generation of Th 1 cells. Both IL-12 and IL-12 antagonists are being studied for the treatment of allergic reactions, autoimmune disease and malignancy. The goal of the present experiments was to examine the importance of IL-12 in endotoxin-induced ocular inflammation. The number of inflammatory cells infiltrating eyes with endotoxin-induced uveitis (EIU) was significantly increased in animals treated with intraperitoneal anti-IL-12 antibody when compared to control animals, but there was no difference in infiltrating inflammatory cells in the eyes of animals treated with IL-12 when compared to controls. In contrast, intraocular injection of IL-12 significantly inhibited the development of endotoxin-induced intraocular inflammation. The inflammatory cells were reduced in the eves of animals receiving intraocular IL-obtained from eyes with EIU showed increased levels of IFN-gamma and decreased levels of IL-6 in eyes receiving intraocular IL-12. These data show that IL-12 has an inhibitory effect on endotoxin-induced inflammation in the eye and su that IL-12 can have an immunoregulatory function in some forms of inflammatory disease. C1 NIH,HOWARD HUGHES MED INST,SCHOLARS PROGRAM,BETHESDA,MD 20892. ESCOLA PAULISTA MED,SAO PAULO,BRAZIL. NIAID,NIH,BETHESDA,MD 20892. UNIV FED MINAS GERAIS,DEPT BIOCHEM & IMMUNOL,BELO HORIZONT,MG,BRAZIL. RP Whitcup, SM (reprint author), NEI,10 CTR DR,BLDG 10,RM 10N202,BETHESDA,MD 20892, USA. RI Rizzo, Luiz Vicente/B-4458-2009 NR 33 TC 18 Z9 19 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAY PY 1996 VL 26 IS 5 BP 995 EP 999 DI 10.1002/eji.1830260506 PG 5 WC Immunology SC Immunology GA UT531 UT WOS:A1996UT53100005 PM 8647191 ER PT J AU Gossard, JP Floeter, MK Degtyarenko, AM Simon, ES Burke, RE AF Gossard, JP Floeter, MK Degtyarenko, AM Simon, ES Burke, RE TI Disynaptic vestibulospinal and reticulospinal excitation in cat lumbosacral motoneurons: Modulation during fictive locomotion SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE Deiters' nucleus; medial longitudinal fasciculus; fictive locomotion; spinal cord; interneurons; decerebrate cat ID MEDIAL LONGITUDINAL FASCICULUS; LATENCY CUTANEOUS EXCITATION; DESCENDING PATHWAYS; ALPHA-MOTONEURONES; PHASIC MODULATION; SPINAL-CORD; GROUP-I; FLEXOR; INTERNEURONS; STIMULATION AB This study compares some characteristics of the disynaptic excitatory pathways from the lateral vestibular nucleus (LVN) and medial longitudinal fasciculus (MLF) to lumbosacral alpha-motoneurons in the decerebrate cat. We used the spatial facilitation technique to test whether disynaptic LVN and MLF excitatory postsynaptic potentials (EPSPs) are produced by common last-order interneurons in the lumbosacral segments of the spinal cord. Of 77 motoneurons examined, 26 exhibited disynaptic EPSPs from both supraspinal sources. No spatial facilitation was found between LVN and MLF EPSPs in 21 of 24 cells that were adequately tested. In 3 of 23 cells (all flexor motoneurons), some spatial facilitation was found in some but not all trials. These observations suggest that stimulation of the LVN and MLF produces disynaptic EPSPs in motoneurons through largely separate populations of last-order interneurons. Disynaptic MLF and LVN EPSPs showed parallel patterns of modulation during fictive locomotion. Maximal disynaptic EPSP amplitudes occurred during the phase of the step cycle when the recorded motoneuron, whether flexor or extensor, exhibited depolarizing locomotor drive potentials and the corresponding muscle nerve was active. These observations, taken together, suggest that disynaptic LVN and MLF EPSPs are produced in motoneurons by at least four separate populations of segmental last-order excitatory interneurons, with separate populations projecting to flexor versus extensor cells. The results also suggest that the modulation of the disynaptic EPSPs during fictive locomotion is mainly due to premotoneuronal convergence of input from the respective descending systems and from the segmental central pattern generator for locomotion onto common interneurons. C1 NIH,NEURAL CONTROL LAB,BETHESDA,MD 20892. NR 45 TC 38 Z9 38 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD MAY PY 1996 VL 109 IS 2 BP 277 EP 288 PG 12 WC Neurosciences SC Neurosciences & Neurology GA UK469 UT WOS:A1996UK46900008 PM 8738376 ER PT J AU Bush, GA Miles, FA AF Bush, GA Miles, FA TI Short-latency compensatory eye movements associated with a brief period of free fall (vol 108, pg 337, 1995) SO EXPERIMENTAL BRAIN RESEARCH LA English DT Correction, Addition RP Bush, GA (reprint author), NIH,SENSORIMOTOR RES LAB,BLDG 49,ROOM 2A50,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD MAY PY 1996 VL 109 IS 2 BP 366 EP 366 PG 1 WC Neurosciences SC Neurosciences & Neurology GA UK469 UT WOS:A1996UK46900016 ER PT J AU Fujio, K Hu, ZY Evarts, RP Marsden, ER Niu, CH Thorgeirsson, SS AF Fujio, K Hu, ZY Evarts, RP Marsden, ER Niu, CH Thorgeirsson, SS TI Coexpression of stem cell factor and c-kit in embryonic and adult liver SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; RAT-LIVER; HEPATIC DIFFERENTIATION; EXPRESSION; RECEPTOR; LIGAND; LOCUS; PROTOONCOGENE; PROLIFERATION; MUTATIONS AB Stem cell factor and its receptor c-kit constitute an important signal transduction system implicated in survival, proliferation, and differentiation of stem cells in hematopoiesis, gametogenesis, and melanogenesis. In the present study we used both immunocytochemical methods and Western analysis to demonstrate the presence of this cytokine/receptor system in both embryonic and adult rat Liver. Stem cell factor was present in the ductular cells around the portal vein during the late embryonic stage of the liver. In the adult liver both bile ducts and bile ductules were positive for stem cell factor and c-kit. When the activation of the liver stem cell compartment was induced by combining administration of acetylaminofluorene and partial hepatectomy, both stem cell factor and c-kit were expressed in the infiltrating oval cell population, but absent in the newly formed basophilic hepatocytes. Activation of oval cell proliferation following administration of D-galactosamine also produced a similar but less prominent increase in the level of the stem cell factor. Our data suggest that the stem cell faetor/c-kit signal transduction system is involved in the development of bile ducts and that it may also be an important member of the growth factor/receptor systems associated with the biology of liver stem cells. (C) 1996 Academic Press, Inc. C1 NCI,NIH,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 29 TC 61 Z9 61 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAY 1 PY 1996 VL 224 IS 2 BP 243 EP 250 DI 10.1006/excr.1996.0134 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA UJ210 UT WOS:A1996UJ21000004 PM 8612701 ER PT J AU Webb, DK Evans, MK Bohr, VA AF Webb, DK Evans, MK Bohr, VA TI DNA repair fine structure in Werner's syndrome cell lines SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID VARIEGATED TRANSLOCATION MOSAICISM; MOLECULAR-GENETIC HYPOTHESIS; CULTURED SKIN FIBROBLASTS; XERODERMA-PIGMENTOSUM; CHROMOSOMAL REARRANGEMENTS; COCKAYNES-SYNDROME; LYMPHOCYTES; INVIVO; INSTABILITY; INDIVIDUALS AB Werner's syndrome (WS) is a human segmental progerioid disorder with an autosomal recessive pattern of inheritance. Patients with WS exhibit a number of symptoms resembling a premature aging phenotype. We have examined the fine structure of the DNA repair of UV-induced cyclobutane pyrimidine dimers in Epstein-Barr virus (EBV)-transformed WS lymphoblastoid cell lines and in a primary WS fibroblast cell line. The repair was measured at the level of the gene and also in the general genome. Gene-specific and strand-specific DNA repair was measured in the actively transcribed genes dihydrofolate reductase (DRFR), c-myc, and p53, and in the transcriptionally inactive regions, delta globin and the X-linked 754 domain. Both gene-specific repair and strand-specific repair were deficient in the transformed WS lymphoblastoid cell lines compared to normal controls. In normal cells, repair in the transcribed strand was 25 (4 h), 43 (8 h), and 72% (24 h); in the WS cells on average, repair in the transcribed strand was 18 (4 h), 27 (8 h), and 44% (24 h). However, in the primary WS fibroblast cell line, we found a pattern of preferential gene repair which was similar to that in normal human cells, In contrast to cells from patients with the gene-specific repair deficient disease Cockayne's syndrome, which show greatly delayed RNA synthesis recovery after UV irradiation, the WS cells had normal recovery of RNA synthesis. The DNA repair results differ for the different cell types, and our findings thus do not establish a general DNA repair phenotype for WS cells. The fibroblasts had proficient repair, but in the WS lymphoblasts we find a deficiency in DNA repair which could contribute to the reported hypermutability in these cells. The lymphoblasts are, however, transformed cells, and it raises the concern that biological findings in transformed cells may not reflect the situation in primary cells. (C) 1996 Academic Press, Inc. C1 NIA,NIH,GENET MOLEC LAB,BALTIMORE,MD 21224. NR 51 TC 30 Z9 30 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAY 1 PY 1996 VL 224 IS 2 BP 272 EP 278 DI 10.1006/excr.1996.0137 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA UJ210 UT WOS:A1996UJ21000007 PM 8612704 ER PT J AU Schefer, V Talan, MI AF Schefer, V Talan, MI TI Oxygen consumption in adult and aged C57BL/6J mice during acute treadmill exercise of different intensity SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE age; maximal aerobic capacity; submaximal and maximal oxygen consumption ID RESPONSES; MEN AB Submaximal and maximal oxygen consumption was determined in untrained adult and aged male C57BL/6J mice during treadmill running, Each of 12-month-old (ADULT) and 24-month-old (AGED) male mice was tested on a motor-driven treadmill once at different speeds. VO2 was measured before, during, and after exercise by means of indirect calorimetry in metabolic treadmill chambers. The resting VO2 averaged 3064.67 +/- 87.71 mL/kg/h for ADULT mice and 2472.95 +/- 69.41 mL/kg/h for AGED mice. During exercise, VO2 increased linearly with work intensity (running speed): ADULT mice - from 5908.06 +/- 422.35 mL/kg/h at 3 m/min to 10861.99 +/- 174.03 mL/kg/h at 25 m/min; AGED mice - from 5217.25 +/- 263.26 mL/kg/h at 3 m/min to 7817.32 +/- 290.28 mL/kg/h at 20 m/min. Further increase of the running speed resulted in a decline of VO2 in ADULT and refusal to run in AGED mice. The results of this study demonstrated that in untrained C57BL/6J mice VO(2)max and maximal exercise capacity declined with age. At the same absolute and relative workloads, VO2 was lower in AGED mice. C1 NIA,GERONTOL RES CTR,BEHAV SCI LAB,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. RI Schefer, Jurg/G-3960-2012 NR 14 TC 73 Z9 73 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD MAY-JUN PY 1996 VL 31 IS 3 BP 387 EP 392 DI 10.1016/0531-5565(95)02032-2 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA UN728 UT WOS:A1996UN72800005 PM 9415121 ER PT J AU Kirov, SA Talan, MI Kosheleva, NA Engel, BT AF Kirov, SA Talan, MI Kosheleva, NA Engel, BT TI Nonshivering thermogenesis during acute cold exposure in adult and aged C57BL/6J mice SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE body temperature; brown adipose tissue; cold tolerance; heat production; mitochondria; rodents; thermogenin; thermoregulation; uncoupling protein ID METABOLIC HEAT-PRODUCTION; BROWN ADIPOSE-TISSUE; RATS; STRESS; TOLERANCE; BINDING AB In C57BL/6J adult and aged mice, housed at room temperature (22.5 +/- 1 degrees C), we measured O-2 consumption and CO2 production and calculated metabolic heat production under conditions of anesthesia and myorelaxation during acute cold stimulation when body temperature was lowered 7.5 degrees C below control level. An independent group of mice was subjected to a three hour partial physical restraint at 6 degrees C and concentration of uncoupling protein (thermogenin) was measured in interscapular brown adipose tissue mitochondria at different times after cold exposure. Heat production under anesthesia and myorelaxation was about 57-66% lower than in nonanesthetized conditions, but increased significantly during cold stimulation in both age groups. Under anesthesia and myorelaxation before and during cold stimulation aged mice produced about 20% more heat than adult mice. Because in these experiments all sources of facultative thermogenesis, except nonshivering, were suppressed by anesthesia and myorelaxation, and because brown adipose tissue is the major source of nonshivering thermoproduction, we concluded that aged mice housed at room temperature have an increased thermogenesis in brown adipose tissue. This conclusion was also supported by the finding that the concentration of uncoupling protein measured in the mitochondria of brown adipose tissue after single cold exposure was significantly higher in aged than in adult mice. Therefore, we propose that the lower, cold-induced, heat production typically observed in nonanesthetized aged mice may reflect reduced thermogenic capacity of skeletal muscles. While aged mice have less brown adipose tissue than adult animals, the remaining brown adipose tissue may compensate by increasing the concentration of uncoupling protein. C1 NIA,GERONTOL RES CTR,BEHAV SCI LAB,BALTIMORE,MD 21224. NR 30 TC 11 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD MAY-JUN PY 1996 VL 31 IS 3 BP 409 EP 419 DI 10.1016/0531-5565(95)02035-7 PG 11 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA UN728 UT WOS:A1996UN72800007 PM 9415123 ER PT J AU Knusel, B Kaplan, DR Hefti, F AF Knusel, B Kaplan, DR Hefti, F TI Intraparenchymal NGF injections in adult and aged rats induce long-lasting Trk tyrosine phosphorylation SO EXPERIMENTAL NEUROLOGY LA English DT Article ID NERVE GROWTH-FACTOR; MESSENGER-RNA; NEUROTROPHIC FACTOR; FOREBRAIN NEURONS; RECEPTOR; BRAIN; SYSTEM; EXPRESSION; BINDING; GENE AB Neurotrophic factors, particularly the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and related molecules are proposed for the experimental treatment of neurodegenerative disease. Earlier observations had suggested down-regulation of the neurotrophin receptor response with chronic stimulation. We therefore tested for effects of acute and chronic NGF treatment in vivo on the tyrosine phosphorylation response of Trk-type neurotrophin receptors in adult and aged rats, Rats were treated for 1 week with daily injections of NGF directly into the striatum. Surprisingly, this chronic neurotrophin treatment induced long-lasting tyrosine phosphorylation of Trk type receptors beyond the last injection, A similar result was obtained with 1 week of daily injections of BDNF into the hippocampus. Persistent Trk tyrosine phosphorylation was also observed after single neurotrophin injections. With 1 mu g of NGF injected, Trk-type receptors were maximally stimulated from immediately after the injection until 3 days after the treatment, Maintaining Trk tyrosine phosphorylation required maintained energy levels in the tissue. Incubation of microslices of brain tissue from NGF-injected animals in glucose-free buffer completely abolished all Trk tyrosine phosphorylation signals. Recovery of the tissue in presence of glucose restored the signals in microslices derived from NGF-injected animals, in absence of acute NGF treatment. This result, together with dose-response comparisons after 2-h and 2-day survival times suggest that Trk protein remains tyrosine phosphorylated due to trophic protein which is only slowly being cleared out of the tissue during several days after the injection, Experiments with aged rats indicated similar extent and duration of Trk receptor activation after NGF administration in young adult and in aged brain. (C) 1996 Academic Press, Inc. C1 UNIV SO CALIF,DEPT BIOL SCI,LOS ANGELES,CA 90089. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,EUKARYOT SIGNAL TRANSDUCT GRP,FREDERICK,MD 21702. RP Knusel, B (reprint author), UNIV SO CALIF,DIV NEUROGERONTOL,ANDRUS GERONTOL CTR,LOS ANGELES,CA 90089, USA. FU NIA NIH HHS [AG09793, AG10480.]; NINDS NIH HHS [NS22933] NR 56 TC 32 Z9 32 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 1996 VL 139 IS 1 BP 121 EP 130 DI 10.1006/exnr.1996.0087 PG 10 WC Neurosciences SC Neurosciences & Neurology GA UK439 UT WOS:A1996UK43900014 PM 8635559 ER PT J AU Desai, NC Bhatt, JJ Shah, BR Undavia, NK Trivedi, PB Narayanan, V AF Desai, NC Bhatt, JJ Shah, BR Undavia, NK Trivedi, PB Narayanan, V TI Synthesis of substituted quinazolone derivatives as potential anti-HIV agents .3. SO FARMACO LA English DT Article ID ANTIMICROBIAL ACTIVITY; 5-ARYLIDINE DERIVATIVES; 4-THIAZOLIDINONES AB Several 1-[2-phenyl-4(4H)-oxo-3-quinazolinyl]-2-methyl-4-arylidine-5-oxo-imidazolines (Va-l), 2-phenyl-3-(aroyl amino)-4(4H)-oxo quinazolines (Vla-I) and N-1-2-methyl-4(4H)-oxo-3-quinazolinyl-N-2-aryl-thioureas (Vlla-k), have been synthesised and tested for anti-HIV activity. The structures of these compounds have been established on the basis of elemental analysis and spectral data. C1 NCI,DRUG SYNTH & CHEM BRANCH,BETHESDA,MD. RP Desai, NC (reprint author), BHAVNAGAR UNIV,DEPT CHEM,BHAVNAGAR 364002,GUJARAT,INDIA. NR 12 TC 14 Z9 14 U1 0 U2 0 PU SOC CHIMICA ITALIANA PI ROME PA VIALE LIEGI 48, I-00198 ROME, ITALY SN 0014-827X J9 FARMACO JI Farmaco PD MAY PY 1996 VL 51 IS 5 BP 361 EP 366 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UT443 UT WOS:A1996UT44300005 PM 8767846 ER PT J AU Negishi, M Uno, T Darden, TA Sueyoshi, T Pedersen, LG AF Negishi, M Uno, T Darden, TA Sueyoshi, T Pedersen, LG TI Structural flexibility and functional versatility of mammalian P450 enzymes SO FASEB JOURNAL LA English DT Review DE DHEA; specificity; polarity; substrate recognition sites; side chains ID SITE-DIRECTED MUTAGENESIS; AMINO-ACID; COUMARIN 7-HYDROXYLASE; STEROID 15-ALPHA-HYDROXYLASE; SUBSTRATE-SPECIFICITY; II P-45015-ALPHA; CYTOCHROME-P450; MUTATION; CYTOCHROMES-P450; HYDROXYLATION AB P450 enzymes have evolved into a large superfamily that displays great diversity in substrate and product specificities by fixing the natural amino acid substitutions with high frequency. Site-directed mutagenesis has been used to correlate the substitutions with the diverse specificities in various P450s. As a result, the common residues that determine the specificities of various mammalian P450s have been identified and aligned to the corresponding residues in the substrate-heme pocket of the 3-dimensional structures of bacterial P450s. The substrate-heme pocket appears to be structurally variable so that only a minor substitution (Ala -->--> Val, for example) at the critical positions is enough to define the altered specificity. Thus, the structural variability of the P450s provides the inherent versatility in acquiring a novel activity. Recent mutational studies indicate that the side chain size is the major determining factor of specificity, outweighing other factors such as polarity. Further understanding of the paradoxical characteristics observed may provide us with the underlying principles that determine P450 activities, and may lead to the ability to predict P450 activities based on the types of key amino acid residues. C1 NIEHS,LAB QUANTITAT & COMP BIOL,NIH,RES TRIANGLE PK,NC 27709. RP Negishi, M (reprint author), NIEHS,REPROD & DEV TOXICOL LAB,PHARMACOGENET SECT,NIH,RES TRIANGLE PK,NC 27709, USA. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 NR 34 TC 59 Z9 63 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY PY 1996 VL 10 IS 7 BP 683 EP 689 PG 7 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UN798 UT WOS:A1996UN79800002 PM 8635685 ER PT J AU Chhabra, SK Perella, C Anderson, LM AF Chhabra, SK Perella, C Anderson, LM TI Induction of hepatic and renal P4502E1 of neonatal rats exposed translactationally to ethanol SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article ID N-NITROSODIMETHYLAMINE DEMETHYLASE; BREAST-MILK; NITROSAMINE METABOLISM; CYTOCHROME P-4502E1; PRENATAL ALCOHOL; HUMAN-LIVER; EXPRESSION; PROTEINS; CONSUMPTION; CHEMICALS AB The effect of maternal ethanol intake during lactation on neonatal cytochrome P4502E1 was investigated in Sprague-Dawley rats. Dams were exposed to 15% (v/v) ethanol in drinking water from day 1 of lactation to 4, 7 or 14 days postpartum Significant (P < 0.01) enhancement of both hepatic and renal N-nitrosodimethylamine (NDMA) demethylase, an activity of P4502E1, was observed in lactating mothers given ethanol in drinking water. Demethylase activity also significantly increased (P < 0.01) in the 7- and 14-day livers of both female and male pups and in the 7- and 14-day female and 14-day male kidneys exposed to ethanol through the transmammary route. Cytochrome P4502E1 protein content, assayed by immunoblotting, increased in the maternal liver and kidney of all groups consuming ethanol. Neonatal P4502E1 protein content increased in the 7- and 14-day livers of both sexes and 14-day female kidneys exposed translactationally to ethanol. No effect of ethanol on enzyme activity or protein content of P4502E1 was observed in the liver or kidney of I-day-old neonates. These results demonstrate the translactational effect of ethanol on neonatal P4502E1 enzyme, which is involved in the metabolism of many low molecular weight xenobiotics, and indicate the possibility of alterations occurring in the kinetics of neonatal drug and xenobiotic metabolism and also in processes connected with perinatal carcinogenesis. C1 SAIC FREDERICK, LAB ANIM SCI PROGRAM, FREDERICK, MD 21702 USA. RP Chhabra, SK (reprint author), NCI, FREDERICK CANC RES & DEV CTR, PERINATAL CARCINOGENESIS SECT, COMPARAT CARCINOGENESIS LAB, FREDERICK, MD 21702 USA. NR 47 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD MAY PY 1996 VL 34 IS 5 BP 469 EP + DI 10.1016/0278-6915(96)87357-1 PG 0 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA UQ161 UT WOS:A1996UQ16100005 PM 8655096 ER PT J AU Bucher, JR Portier, CJ Goodman, JI Faustman, EM Lucier, GW AF Bucher, JR Portier, CJ Goodman, JI Faustman, EM Lucier, GW TI National toxicology program studies: Principles of dose selection and applications to mechanistic based risk assessment SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Editorial Material ID ANIMAL CARCINOGENICITY; DESIGN; MODELS; TESTS AB A workshop entitled ''NTP Studies: Principles of Dose Selection and Applications to Mechanistic Based Risk Assessment'' was held at the 34th Annual Meeting of the Society of Toxicology in Baltimore, Maryland. The purpose of the workshop was to provide an overview of factors currently considered important in the selection of doses for NTP studies, to describe some of the confounding factors that can result from the indiscriminate use of bioassay data in quantitative risk assessment; and to suggest ways in which information from mechanistic studies or studies of biomarkers of exposure or effect might be used to better advantage in risk assessment. (C) 1996 Society of Toxicology C1 MICHIGAN STATE UNIV,DEPT PHARMACOL,E LANSING,MI 48824. UNIV WASHINGTON,DEPT ENVIRONM HLTH,SEATTLE,WA 98195. RP Bucher, JR (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 FU NIEHS NIH HHS [ES-05299] NR 37 TC 32 Z9 32 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD MAY PY 1996 VL 31 IS 1 BP 1 EP 8 DI 10.1006/faat.1996.0070 PG 8 WC Toxicology SC Toxicology GA UK513 UT WOS:A1996UK51300001 PM 8998945 ER PT J AU Vojta, PJ Futreal, PA Annab, LA Kato, H PereiraSmith, OM Barrett, JC AF Vojta, PJ Futreal, PA Annab, LA Kato, H PereiraSmith, OM Barrett, JC TI Evidence for two senescence loci on human chromosome I SO GENES CHROMOSOMES & CANCER LA English DT Article ID SOMATIC-CELL HYBRIDS; INDEFINITE DIVISION; POSSIBLE INVOLVEMENT; HUMAN FIBROBLASTS; GENETIC-ANALYSIS; HETEROZYGOSITY; LINE; IMMORTALIZATION; INVITRO; PROGRESSION AB Microcell-mediated introduction of a neo-tagged human chromosome 1 (HC-1-neo) into several immortal cell lines has previously been shown to induce growth arrest and phenotypic changes indicative of replicative senescence. Somatic cell hybridization studies have localized senescence activity for immortal hamster 10W-2 cells to a cytogenetically defined region between 1q23 and the q terminus. Previous microcell-mediated chromosome transfer experiments showed that a chromosome 1 with an interstitial q-arm deletion (del-1q) lacks senescence inducing activity for several immortal human cell lines that are sensitive to an intact HC-1-neo. In contrast, our studies reveal that the del-1q chromosome retains activity for 10W-2 cells, indicating that there are at least two senescence genes on human chromosome 1. Sequence-tagged site (STS) content analysis revealed that the q arm of the del-1q chromosome has an interstitial deletion of approximately 63 centimorgans (cM), between the proximal STS marker D1S534 and distal marker D1S412, approximately 1q12 to 1q31. This deletion analysis provides a candidate region for one of the senescence genes on 1q. In addition, because this deletion region extends distally beyond 1q23, it localizes the region containing a second senescence gene to approximately 1q31-qter, between D1S422 and the q terminus. STS content analysis of a panel of 11 10W-2 microcell hybrid clones that escaped senescence identified 2 common regions of loss of 1q material below the distal breakpoint of del-1q. One region is flanked by markers D1S459 and ACTN2, and the second lies between markers WI-4683 and D1S1609, indicating that the distal 1q senescence gene(s) localizes within 1q42-43. (C) 1996 Wiley-Liss, Inc C1 NATL INST ENVIRONM HLTH SCI,NIH,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,CURRICULUM GENET & MOLEC BIOL,CHAPEL HILL,NC. BAYLOR COLL MED,ROY M & PHYLLIS GOUGH HUFFINGTON CTR AGING,DIV MOLEC VIROL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. NR 50 TC 22 Z9 23 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD MAY PY 1996 VL 16 IS 1 BP 55 EP 63 PG 9 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA UJ006 UT WOS:A1996UJ00600008 PM 9162198 ER PT J AU Zhang, SD Kassis, J Olde, B Mellerick, DM Odenwald, WF AF Zhang, SD Kassis, J Olde, B Mellerick, DM Odenwald, WF TI Pollux, a novel Drosophila adhesion molecule, belongs to a family of proteins expressed in plants, yeast, nematodes, and man SO GENES & DEVELOPMENT LA English DT Article DE pollux; Drosophila; adhesion protein; trachea; CNS ID AMINO-ACID SEQUENCE; CELL-ADHESION; SEA-URCHIN; IMMUNOGLOBULIN SUPERFAMILY; EXTRACELLULAR-MATRIX; NEURAL DEVELOPMENT; RECOGNITION; RECEPTORS; GENE; IDENTIFICATION AB Adhesion molecules have pivotal roles in cellular processes critical to the development and maintenance of multicellular organisms. Here we describe a new member of the adhesive repertoire encoded by the Drosophila pollux (pix) gene. Marked by a novel 74-amino-acid domain, Pix belongs to a highly conserved family with members in plants, yeast, nematodes, and man, including the human oncoprotein TRE17. Essential for viability, pix mutant analysis indicates that larval death is attributable to asphyxiation brought on by fluid-congested tracheal tubes. Ultrastructural examination of mutant tracheae reveals defects in cell-extracellular matrix contacts. During embryogenesis, Pix uniformly covers the apical surface of cellular blastoderm cells. It is later found regionally concentrated along subsets of central nervous system axon pathways and on the apical surface of the trachea's tubular epithelium. Cell attachment assays demonstrate that pix can serve as a ligand for cell surface integrins. Pix also contains a motor neuron-selective adhesive site, multiple proteoglycan-binding motifs, and a leucine zipper: all suggest possible associations with additional components of the adhesion complex. C1 NINCDS,NIH,NEUROGENET UNIT,NEUROCHEM LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD. NINCDS,NIH,NEUROGENET CTR,BETHESDA,MD 20892. OI Kassis, Judith/0000-0001-9268-3213 NR 67 TC 29 Z9 29 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 1 PY 1996 VL 10 IS 9 BP 1108 EP 1119 DI 10.1101/gad.10.9.1108 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA UL248 UT WOS:A1996UL24800006 PM 8654926 ER PT J AU Segall, AM Nash, HA AF Segall, AM Nash, HA TI Architectural flexibility in lambda site-specific recombination: Three alternate conformations channel the attL site into three distinct pathways SO GENES TO CELLS LA English DT Article ID BACTERIOPHAGE-LAMBDA; PROTEIN; DNA; INTEGRASE; MUTANT; INT; HOMOLOGY; SEQUENCE; ORDER; RANGE AB Background: In the phage lambda life cycle, the Integrase (Int) protein carries out recombination between two different sets of DNA substrates: attP and attB in integration, attL and attR in excision. In each case, the partners are very different in structure from each other and the recombination reaction between them is effectively irreversible. For comparison, we have studied the recombination mediated by Int between two identical attL sites. Both in vitro and in vivo, recombination between two attL sites can be mediated inefficiently by Int alone. But, while IHF can stimulate recombination 5-10-fold in vivo (to the level of excision and integration), this stimulation is not observed under standard conditions in vitro. Results: We find that IHF can stimulate the in vitro recombination between two attLs that are modified to be defective in one of the high affinity binding sites for Int, P'1. With such substrates, the efficiency of IHF-stimulated recombination is comparable to that seen in vivo. The requirements for this reaction distinguish it from other lambda recombination pathways, as does the performance of several mutant Int proteins. Recombination of attL sites on intracellular plasmids suggests that this pathway is effective in vivo, but that some unknown factor or condition permits it to operate on wild-type as well as mutated attL sites. Conclusions: The recombination pathway described in this work apparently uses a unique attL architecture, one which requires bending by IHF and is inhibited by Int bound at the P'1 site. In addition to demonstrating the architectural flexibity of the lambda system, this pathway should be a valuable resource for separating the basic requirements of strand exchange chemistry from the features which impart directionality. C1 SAN DIEGO STATE UNIV,INST MOL BIOL,SAN DIEGO,CA 92182. NIMH,MOL BIOL LAB,BETHESDA,MD 20892. RP Segall, AM (reprint author), SAN DIEGO STATE UNIV,DEPT BIOL,SAN DIEGO,CA 92182, USA. NR 21 TC 28 Z9 28 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 1356-9597 J9 GENES CELLS JI Genes Cells PD MAY PY 1996 VL 1 IS 5 BP 453 EP 463 DI 10.1046/j.1365-2443.1996.d01-254.x PG 11 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA VC846 UT WOS:A1996VC84600005 PM 9078377 ER PT J AU Berger, R Theodor, L Shoham, J Gokkel, E BrokSimoni, F Avraham, KB Copeland, NG Jenkins, NA Rechavi, G Simon, AJ AF Berger, R Theodor, L Shoham, J Gokkel, E BrokSimoni, F Avraham, KB Copeland, NG Jenkins, NA Rechavi, G Simon, AJ TI The characterization and localization of the mouse thymopoietin lamina-associated polypeptide 2 gene and its alternatively spliced products SO GENOME RESEARCH LA English DT Article ID AMINO-ACID-SEQUENCE; TRANSCRIPTION; PHOSPHORYLATION; THYMOPENTIN; CHROMOSOMES; EXPRESSION; PROTEINS; BINDING; CLONING AB Thymopoietins (Tmpos) are a group of ubiquitously expressed nuclear proteins, with sequence homology to lamina-associated polypeptide 2 (LAP2). Here we report the isolation and characterization of seven mouse Tmpo mRNA transcripts named Tmpo alpha, beta, beta', gamma, epsilon, delta, and zeta. The alpha, beta, and gamma Tmpo cDNA clones are the mouse homologs of the previously characterized human alpha, beta, and gamma TMPOs, respectively, whereas Tmpo epsilon, delta, and zeta are novel cDNAs. Additionally, the mouse Tmpo gene was cloned and characterized. It is a single-copy gene organized in 10 exons spanning similar to 22 kb, which encodes all of the described Tmpo cDNA sequences, located in the central region of mouse chromosome 10, The almost identical genomic organization between the human and mouse genes, and the novel alternatively spliced mouse transcripts, led us to reanalyze the human TMPO gene. The human beta-specific domain was found to be encoded by 3 exons designated 6a, 6b, and 6c and not by a single exon as described previously. These findings suggest that there may be more human transcripts than currently recognized, The possible involvement of the new growing family of Tmpo proteins in nuclear architecture and cell cycle control is discussed. C1 CHAIM SHEBA MED CTR,INST HEMATOL,IL-52621 TEL HASHOMER,ISRAEL. TEL AVIV UNIV,SACKLER SCH MED,IL-69978 TEL AVIV,ISRAEL. BAR ILAN UNIV,FAC LIFE SCI,RAMAT GAN,ISRAEL. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NIGMS NIH HHS [5F32GM15909-02] NR 29 TC 97 Z9 101 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 GENOME RES JI Genome Res. PD MAY PY 1996 VL 6 IS 5 BP 361 EP 370 DI 10.1101/gr.6.5.361 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA UM831 UT WOS:A1996UM83100002 PM 8743987 ER PT J AU Su, XZ Wellems, TE AF Su, XZ Wellems, TE TI Toward a high-resolution Plasmodium falciparum linkage map: Polymorphic markers from hundreds of simple sequence repeats SO GENOMICS LA English DT Article ID HUMAN MALARIA PARASITES; GENETIC CROSS; DNA; CULTURE; GENOME; RATES; MOUSE; PCR AB A total of 507 simple sequence repeats (SSRs or ''microsatellites'') were identified from Plasmodium falciparum sequences in GenBank and from inserts in a genomic DNA library. Oligonucleotide primers from sequences that flank 224 of these SSRs were synthesized and used in PCR assays to test for simple sequence length polymorphisms (SSLPs). Of the 224 SSRs, 188 showed SSLPs among 12 different P. falciparum lines; 116 of these SSLPs were assigned to chromosome Linkage groups by physical mapping and by comparing their inheritance patterns against those of restriction fragment length polymorphism markers in a genetic cross (HE3xDd2). The predominant SSLPs in P. falciparum were found to contain [TA](n), [T](n), and [TAA](n), a feature that-is reminiscent of plant genomes and is consistent with the proposed algal-like origin of malaria parasites. Since such SSLPs are abundant and readily isolated, they are a powerful resource for genetic analysis of P. falciparum. (C) 1996 Academic Press, Inc. C1 NIAID,LPD,NIH,BETHESDA,MD 20892. OI Su, Xinzhuan/0000-0003-3246-3248 NR 38 TC 122 Z9 125 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAY 1 PY 1996 VL 33 IS 3 BP 430 EP 444 DI 10.1006/geno.1996.0218 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA UK511 UT WOS:A1996UK51100010 PM 8661002 ER PT J AU Lomako, J Mazuruk, K Lomako, WM Alonso, MD Whelan, WJ Rodriguez, IR AF Lomako, J Mazuruk, K Lomako, WM Alonso, MD Whelan, WJ Rodriguez, IR TI The human intron-containing gene for glycogenin maps to chromosome 3, band q24 SO GENOMICS LA English DT Article ID SKELETAL-MUSCLE GLYCOGENIN AB Glycogenin is the autocatalytic, self-glucosylating primer for glycogen synthesis, providing the anchor on which the macromolecule is constructed. We have sequenced the cDNA coding for human muscle glycogenin and have deduced the corresponding amino acid sequence. By means of the polymerase chain reaction and fluorescence in situ hybridization, we have found the chromosomal location of the gene coding for glycogenin. This is localized to human chromosome 3, band q24. (C) 1996 Academic Press, Inc. C1 UNIV MIAMI,SCH MED,DEPT BIOCHEM & MOLEC BIOL,MIAMI,FL 33101. NEI,RETINAL CELL & MOLEC BIOL LAB,NIH,BETHESDA,MD 20892. FU NIDDK NIH HHS [DK 37500] NR 6 TC 8 Z9 9 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAY 1 PY 1996 VL 33 IS 3 BP 519 EP 522 DI 10.1006/geno.1996.0228 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA UK511 UT WOS:A1996UK51100020 PM 8661012 ER PT J AU Muirhead, CR Boice, JD Raddatz, CT Yoder, RC AF Muirhead, CR Boice, JD Raddatz, CT Yoder, RC TI Comparison of dose histories for US nuclear power plant workers, based on records held by a major dosimetry service company and on the NRC reirs database SO HEALTH PHYSICS LA English DT Article DE dosimetry; epidemiology; exposure, occupational; nuclear power plant ID MORTALITY; RADIATION; INDUSTRY AB In order to conduct valid epidemiological studies of nuclear power plant workers, good information on the workers' radiation dose histories is essential, Dose records held by a major dosimetry service company and on the Nuclear Regulatory Commission's Radiation Exposure Information and Recording System have been compared for a sample of 99 workers. About half of the workers in the sample had no records on the Radiation Exposure Information and Recording System, since they had not terminated employment at a Nuclear Regulatory Commission-licensed facility; accordingly, their career doses (as recorded by the service company) were generally higher than those for workers on the Radiation Exposure Information and Recording System, For nearly half of the workers with records on both databases, the total dose recorded for terminated employments at nuclear power plants differed by at least a factor of 5 between the databases. In absolute terms, these differences were of the order of 100 mSv or more. An approach that utilizes both the Radiation Exposure Information and Recording System and the dosimetry service company's records might be of value in constructing dose histories for a large epidemiological study. However, the comparisons presented here support the initiatives of the Nuclear Regulatory Commission to request licensees to report voluntarily career doses for current employees, These data are essential if a large and valid epidemiological study of nuclear plant workers is to be conducted in the foreseeable future. C1 NCI, RADIAT EPIDEMIOL BRANCH, ROCKVILLE, MD 20852 USA. LANDAUER INC, GLENWOOD, IL 60425 USA. US NUCL REGULATORY COMMISS, RADIAT PROTECT & HLTH EFFECTS BRANCH, WASHINGTON, DC 20555 USA. RP Muirhead, CR (reprint author), NATL RADIOL PROTECT BOARD, DIDCOT OX11 0RQ, OXON, ENGLAND. NR 9 TC 6 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD MAY PY 1996 VL 70 IS 5 BP 645 EP 650 DI 10.1097/00004032-199605000-00004 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA UF094 UT WOS:A1996UF09400006 PM 8690574 ER PT J AU Kurokohchi, K Carrington, M Mann, DL Simonis, TB AlexanderMiller, MA Feinstone, SM Akatsuka, T Berzofsky, JA AF Kurokohchi, K Carrington, M Mann, DL Simonis, TB AlexanderMiller, MA Feinstone, SM Akatsuka, T Berzofsky, JA TI Expression of HLA class I molecules and the transporter associated with antigen processing in hepatocellular carcinoma SO HEPATOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; HEPATOMA-CELL LINE; LYMPHOCYTE-T; GENES; MHC; RECOGNITION; SPECIFICITY; PEPTIDES; REGION AB The expression of the HLA class I molecules on the cell surface was investigated in hepatocellular carcinoma (HCC) cell lines using complement-mediated cytotoxicity (CMC) and flow cytometric analysis, Although HLA-A antigens were detected by CMC in all cell Lines tested, HLA-B and-C antigens were not detectable in six of seven HCC cell lines. These results were also confirmed by now cytometric analysis focusing on HLA-Bw4 and Bw6 public antigens, Furthermore, complementary DNA (cDNA) hom each cell line was tested for the expression of HLA-A, -B, -C and the transporter associated with antigen processing genes (TAP1 and TAP2). Two cell lines showed a reduced level of one or both of the TAP messenger RNAs (mRNAs), and one of these showed a reduction of HLA-B and -C gene expression as well, but the others had detectable mRNA levels. These results demonstrate that hepatocellular carcinoma cell lines tested in the current study lose or decrease the expression of HLA-B and -C alleles on the cell surface, even though mRNA encoding these alleles is present, suggesting that the loss of the HLA molecules might be caused by posttranscriptional events or failure to transport and load peptides necessary for HLA expression, The selective loss of HLA-B and -C, but not -A, molecules (which also excludes a beta(2)-microglobulin defect) is intriguing, and may be attributable to the ability of some of the HLA-A molecules to load signal peptides not requiring TAP transport, or to natural selection by HLA-B or -C locus-specific immune surveillance. C1 NCI,METAB BRANCH,MOLEC IMMUNOGENET & VACCINE RES SECT,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD. NIH,DEPT TRANSFUS MED,CTR CLIN,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,LAB HEPATITIS RES,BETHESDA,MD. NR 45 TC 54 Z9 58 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 1996 VL 23 IS 5 BP 1181 EP 1188 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UJ443 UT WOS:A1996UJ44300037 PM 8621152 ER PT J AU Williams, AO Knapton, AD AF Williams, AO Knapton, AD TI Hepatic silicosis, cirrhosis, and liver tumors in mice and hamsters: Studies of transforming growth factor beta expression SO HEPATOLOGY LA English DT Article ID INDUCED PULMONARY FIBROSIS; MESSENGER-RNA EXPRESSION; RAT-LIVER; CRYSTALLINE SILICA; CELL-PROLIFERATION; COLLAGEN FORMATION; NECROSIS-FACTOR; FACTOR-ALPHA; TGF-BETA; FACTOR-BETA-1 AB Hepatic silicosis, cirrhosis, liver cell adenoma, and carcinomas developed in nude mice (NCr-Nu) given quartz by the subcutaneous and intraperitoneal routes, Syrian golden hamsters (15:16 EHS:cr) given quartz by both routes developed extensive fibrosis and cirrhosis and had higher morbidity and mortality rates after 3 months. Crystalline silica (quartz) induces fibrosis, adenomas, and carcinomas in the lungs of Fisher 344 rats, but certain strains of mice and hamsters are resistant to quartz-induced pulmonary carcinogenesis. Pulmonary fibrosis, however, is minimal in mice and absent in hamsters who received quartz intratracheally. To determine whether species differences are due to organ-specific rather than species-specific factors, susceptibility of the liver to quartz toxicity was investigated in nude mice and hamsters, The present study shows that the differential manifestations of quartz toxicity by these rodent species are dependent on factors that are organ-specific rather than host-specific. At 3 months, hepatocytes in mice were immunostained with intracellular transforming growth factor (TGF) beta 1 (LC 1-30) but not with TGF-beta 1 latency-associated peptide (LAP) protein (266-278); at 12 months, hepatocytes were immunostained with TGF-beta 1 LAP (266-278) but not with TGF-beta 1 (LC1-30). The hepatocytes of hamsters at 3 months showed immunoreactivities to TGF-beta 1 LAP (266-278) and TGF-beta 1 (LC1-30); immunostaining to TGF-beta 1 (LC1-30) was detected in nonparenchymal cells. Extracellular TGF-beta 1 (CC1-30) was detected in the silicotic granulomas and fibrous tissue in livers of both species. Quartz-induced liver carcinoma did not express TGF-beta 1 LAP (266-278) and LC (1-30) proteins, but these were detected in the cells of the adenoma in the same liver. Control animals showed no hepatic lesions nor immunoreactivity to TGF-beta 1, The spatial and temporal patterns of expression of TGF-beta 1, TGF-beta 2, TGF-beta receptor type II messenger RNAs (mRNAs), and TGF-beta 1 proteins in the different hepatic lesions suggests that TGF-beta isoforms may play a role in the pathogenesis of quartz induced fibrosis, cirrhosis, liver cell adenoma, and carcinoma. RP Williams, AO (reprint author), NCI, LAB EXPTL PATHOL,DIV CANC ETIOL,BLDG 41, ROOM C-105, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 61 TC 16 Z9 16 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 1996 VL 23 IS 5 BP 1268 EP 1275 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UJ443 UT WOS:A1996UJ44300048 PM 8621163 ER PT J AU Roa, BB Greenberg, F Gunaratne, P Sauer, CM Lubinsky, MS Kozma, C Meck, JM Magenis, RE Shaffer, LG Lupski, JR AF Roa, BB Greenberg, F Gunaratne, P Sauer, CM Lubinsky, MS Kozma, C Meck, JM Magenis, RE Shaffer, LG Lupski, JR TI Duplication of the PMP22 gene in 17p partial trisomy patients with Charcot-Marie-Tooth type-1A neuropathy SO HUMAN GENETICS LA English DT Article ID DISEASE TYPE-1A; INSITU HYBRIDIZATION; POINT MUTATION; P11.2)>; CHROMOSOME-17; PMP-22; CMT1A AB Autosomal dominant Charcot-Marie-Tooth type-1A neuropathy (CMT1A) is a demyelinating peripheral nerve disorder that is commonly associated with a submicroscopic tandem DNA duplication of a 1.5-Mb region of 17p11.2p12 that contains the peripheral myelin gene PMP22. Clinical features of CMT1A include progressive distal muscle atrophy and weakness, foot and hand deformities, gait abnormalities, absent reflexes, and the completely penetrant electrophysiologic phenotype of symmetric reductions in motor nerve conduction velocities (NCVs). Molecular and fluorescence in situ hybridization (FISH) analyses were performed to determine the duplication status of the PMP22 gene in four patients with rare cytogenetic duplications of 17p. Neuropathologic features of CMT1A were seen in two of these four patients, in addition to the complex phenotype associated with 17p partial trisomy. Our findings show that the CMT1A phenotype of reduced NCV is specifically associated with PMP22 gene duplication, thus providing further support for the PMP22 gene dosage mechanism for CMT1A. C1 BAYLOR COLL MED,DEPT MOL & HUMAN GENET,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. BAYLOR COLL MED,CTR HUMAN GENET,HOUSTON,TX 77030. BAYLOR COLL MED,KLEBERG CYTOGENET LAB,HOUSTON,TX 77030. NATL INST HLTH,NATL CTR HUMAN GENOME RES,DIAGNOST DEV BRANCH,BETHESDA,MD 20892. MED COLL WISCONSIN,CHILDRENS HOSP WISCONSIN,GENET CTR,MILWAUKEE,WI 53226. MED COLL WISCONSIN,DEPT PEDIAT,DIV GENET,MILWAUKEE,WI 53226. GEORGETOWN UNIV,MED CTR,DEPT PEDIAT,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,DEPT OBSTET & GYNECOL,WASHINGTON,DC 20007. OREGON HLTH SCI UNIV,DEPT PEDIAT,PORTLAND,OR 97201. FU NINDS NIH HHS [R01NS27042] NR 48 TC 49 Z9 50 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAY PY 1996 VL 97 IS 5 BP 642 EP 649 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA UE049 UT WOS:A1996UE04900019 PM 8655146 ER PT J AU Gracia, E Fischer, U Elkahloun, A Trent, JM Meese, E Meltzer, PS AF Gracia, E Fischer, U Elkahloun, A Trent, JM Meese, E Meltzer, PS TI Isolation of genes amplified in human cancers by microdissection mediated cDNA capture SO HUMAN MOLECULAR GENETICS LA English DT Article ID CHROMOSOME MICRODISSECTION; HUMAN SARCOMAS; AMPLIFICATION; IDENTIFICATION; GLI; HYBRIDIZATION; REGION; CELLS; DNA; RNA AB It has been increasingly recognized that homogeneously staining regions (hsr) in human cancers may be complex structures composed of large amplified DNA domains containing multiple genes, It is therefore important to devise strategies for the rapid isolation of cDNAs expressed from these structures, Using a procedure we term microdissection mediated cDNA capture, we recovered hsr specific cDNAs from two different human tumors. The glioblastoma cell line TX3868 and the human sarcoma cell line OsA-CL carry hsrs containing amplified sequences from chromosome 12q13-15. We recovered 17 hsr specific cDNAs following microdissection of these hsrs which had been previously hybridized in situ with linkered cDNA. Northern blot analysis with these cDNAs revealed hybridization to distinct transcripts in OsA-CL RNA and TX3868 RNA, None of the OsA-CL cDNA clones showed cross hybridization with the TX3868 cDNAs suggesting that despite their coincident band localization on 12q, the OsA-CL and TX3868 amplification units do not completely overlap. These results significantly increase the number of amplified genes assigned to the 12q13-15 amplicon illustrating both the complexity of hsrs derived from this region and the utility of microdissection mediated cDNA capture to gain rapid access to cDNAs transcribed from amplified genes. C1 UNIV SAARLANDES KLINIKEN,INST HUMANGENET,HOMBURG,GERMANY. NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892. NR 30 TC 31 Z9 31 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY PY 1996 VL 5 IS 5 BP 595 EP 600 DI 10.1093/hmg/5.5.595 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA UJ743 UT WOS:A1996UJ74300005 PM 8733125 ER PT J AU Baron, J Winer, KK Yanovski, JA Cunningham, AW Laue, L Zimmerman, D Cutler, GB AF Baron, J Winer, KK Yanovski, JA Cunningham, AW Laue, L Zimmerman, D Cutler, GB TI Mutations in the Ca2+-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism SO HUMAN MOLECULAR GENETICS LA English DT Article ID CONSTITUTIVELY ACTIVE MUTANTS; REGION AB Parathyroid hormone secretion is negatively regulated by a 7-transmembrane domain, G-protein coupled Ca2+-sensing receptor. We hypothesized that activating mutations in this receptor might cause autosomal dominant hypoparathyroidism (ADHP), Consistent with this hypothesis, we identified, in two families with ADHP, heterozygous missense mutations in the Ca2+-sensing receptor gene that cosegregated with the disorder. None of 50 normal controls had either mutation, We also identified a de novo, missense Ca2+-sensing receptor mutation in a child with severe sporadic hypoparathyroidism. The amino acid substitution in one ADHP family affected the N-terminal, extracellular domain of the receptor, The other mutations involved the transmembrane region, Unlike patients with acquired hypoparathyroidism, patients with these mutations had hypercalciuria even at low serum calcium concentrations, Their greater hypercalciuria presumably reflected activation of Ca2+-sensing receptors in kidney cells, where the receptor negatively regulates calcium reabsorption, This augmented hypercalciuria increases the risk of renal complications and thus has implications for the choice of therapy. C1 GEORGETOWN UNIV,MED CTR,DEPT PEDIAT,WASHINGTON,DC 20007. MAYO CLIN,DEPT PEDIAT,ROCHESTER,MN 55905. RP Baron, J (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,NIH,BLDG 10 ROOM 10N262,10 CTR DR MSC 1862,BETHESDA,MD 20892, USA. NR 20 TC 139 Z9 143 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY PY 1996 VL 5 IS 5 BP 601 EP 606 DI 10.1093/hmg/5.5.601 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA UJ743 UT WOS:A1996UJ74300006 PM 8733126 ER PT J AU Margolis, RL Stine, OC McInnis, MG Ranen, NG Rubinsztein, DC Leggo, J Brando, LVJ Kidwai, AS Loev, SJ Breschel, TS Callahan, C Simpson, SG DePaulo, JR McMahon, FJ Jain, S Paykel, ES Walsh, C DeLisi, LE Crow, TJ Torrey, EF AShworth, RG Macke, JP Nathans, J Ross, CA AF Margolis, RL Stine, OC McInnis, MG Ranen, NG Rubinsztein, DC Leggo, J Brando, LVJ Kidwai, AS Loev, SJ Breschel, TS Callahan, C Simpson, SG DePaulo, JR McMahon, FJ Jain, S Paykel, ES Walsh, C DeLisi, LE Crow, TJ Torrey, EF AShworth, RG Macke, JP Nathans, J Ross, CA TI cDNA cloning of a human homologue of the Caenorhabditis elegans cell fate-determining gene mab-21: Expression, chromosomal localization and analysis of a highly polymorphic (CAG)(n) trinucleotide repeat SO HUMAN MOLECULAR GENETICS LA English DT Article ID FRAGILE-X SYNDROME; MYOTONIC-DYSTROPHY; ANDROGEN RECEPTOR; MOEBIUS SYNDROME; BINDING PROTEIN; TRIPLET REPEAT; HUMAN GENOME; RNA-BINDING; CTG REPEAT; CGG REPEAT AB The two most consistent features of the diseases caused by trinucleotide repeat expansion-neuropsychiatric symptoms and the phenomenon of genetic anticipation-may be present in forms of dementia, hereditary ataxia, Parkinsonism, bipolar affective disorder, schizophrenia and autism. To identify candidate genes for these disorders, we have screened human brain cDNA libraries for the presence of gene fragments containing polymorphic trinucleotide repeats. Here we report the cDNA cloning of CAGR1, originally detected in a retinal cDNA library. The 2743 bp cDNA contains a 1077 bp open reading frame encoding 359 amino acids. This amino acid sequence is homologous (56% amino acid identity and 81% amino acid conservation) to the Caenorhabditis elegans cell fate-determining protein mab-21. CAGR1 is expressed in several human tissues, most prominently in the cerebellum, as a message of similar to 3.0 kb. The gene was mapped to 13q13, just telomeric to D13S220. A 5'-untranslated CAG trinucleotide repeat is highly polymorphic, with repeat length ranging from six to 31 triplets and a heterozygosity of 87-88% in 684 chromosomes from several human populations. One allele from an individual with an atypical movement disorder and bipolar affective disorder type II contains 46 triplets, 15 triplets longer than any other allele detected. Though insufficient data are? available to link the long repeat to this clinical phenotype, an expansion mutation of the CAGR1 repeat can be considered a candidate for the etiology of disorders with anticipation or developmental abnormalities, and particularly any such disorders linked to chromosome 13. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT,DIV PSYCHIAT GENET,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DIV PEDIAT INFECT DIS,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED GENET,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MOLEC BIOL & GENET,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,HOWARD HUGHES MED INST,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT OPHTHALMOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,MOLEC & CELLULAR BIOL PROGRAM,BALTIMORE,MD 21205. E ANGLIAN REG GENET SERV MOL GENET LAB,CAMBRIDGE CB2 2QQ,ENGLAND. UNIV CAMBRIDGE,ADDENBROOKES HOSP,DEPT PSYCHIAT,CAMBRIDGE CB2 2QQ,ENGLAND. SUNY STONY BROOK,DEPT PSYCHIAT & BEHAV SCI,NEW YORK,NY 11794. UNIV OXFORD,WARNEFORD HOSP,DEPT PSYCHIAT,OXFORD OX3 7JX,ENGLAND. NATL INST MENTAL HLTH NEUROSCI CTR,WASHINGTON,DC 20032. RP Margolis, RL (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT,MOLEC NEUROBIOL LAB,618 ROSS RES BLDG,720 RUTLAND AVE,BALTIMORE,MD 21205, USA. RI McMahon, Francis/A-7290-2009; McInnis, Melvin/F-6963-2012; Ross, Christopher/H-8395-2013; OI McInnis, Melvin/0000-0002-0375-6247; McMahon, Francis/0000-0002-9469-305X FU NIMH NIH HHS [MH02175-10A1, MH50763]; NINDS NIH HHS [NS34172] NR 82 TC 44 Z9 47 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY PY 1996 VL 5 IS 5 BP 607 EP 616 DI 10.1093/hmg/5.5.607 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA UJ743 UT WOS:A1996UJ74300007 PM 8733127 ER PT J AU Abassi, ZA Pieruzzi, F Nakhoul, F Keiser, HR AF Abassi, ZA Pieruzzi, F Nakhoul, F Keiser, HR TI Effects of cyclosporin A on the synthesis, excretion, and metabolism of endothelin in the rat SO HYPERTENSION LA English DT Article DE endothelins; metabolic clearance rate; cyclosporine; endopeptidase ID ENKEPHALINASE NEUTRAL ENDOPEPTIDASE; SMOOTH-MUSCLE CELLS; RENAL HEMODYNAMICS; GENE-EXPRESSION; MESSENGER-RNA; NEPHROTOXICITY; KIDNEY; TRANSPLANTATION; DYSFUNCTION; THERAPY AB Increasing evidence suggests that endothelin, a potent vasoconstrictor, is implicated in cyclosporin A (CsA)-induced nephrotoxicity. Increased levels of urinary and circulating endothelin have been described in CsA-treated humans and animals. The exact mechanisms by which CsA induces these increases are still unknown, and no data indicate whether these elevated levels reflect increased synthesis or decreased clearance of endothelin. In the present study, we investigated the effects of CsA administration (50 mg/kg per day IP for 6 days) to rats on plasma and urinary levels of endothelin; expression of endothelin-l (ET-1), ET-3, and endothelin-converting enzyme in renal tissue; clearance of infused I-125-ET-1; and degradation of I-125-ET-1 by recombinant neutral endopeptidase. Rats given CsA for 6 days developed severe renal insufficiency, as shown by a 74% decrease in creatinine clearance rate (Ccr) (P<.006). Ccr was remarkably improved in CsA-treated rats that received bosentan, the combined antagonist of both endothelin A and endothelin B receptors. Urinary excretion of endothelin increased from an undetectable level to 31.7+/-6.0 pg/24 h (P<.001), and plasma levels of endothelin were unchanged (2.8+/-0.2 to 3.1+/-0.2 pg/mL). Reverse transcription followed by quantitative polymerase chain reaction revealed that ET-1 mRNA in the renal medulla increased by 59% (P<.006), whereas the expression of both ET-3 and endothelin-converting enzyme was unchanged. In other rats, neither acute nor chronic treatment with CsA affected either the clearance of I-125-ET-1 from the blood or the renal and pulmonary uptake of the peptide. Moreover, CsA did not affect the degradation of I-125-ET-1 by highly purified recombinant neutral endopeptidase, a well-known endothelinase. Taken together, these data suggest that the elevated urinary endothelin levels obtained after CsA treatment originate from the kidney and reflect increased renal synthesis of ET-1. Moreover, the production of endothelin appears to be regulated at the mRNA transcription level, and expressions of ET-1 and ET-3 are regulated independently. C1 NHLBI,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. UNIV MILAN,IST CLIN MED & TERAPIA MED,MILAN,ITALY. OSPED MAGGIORE,CTR FISIOL CLIN & IPERTENS,I-20122 MILAN,ITALY. NR 47 TC 45 Z9 45 U1 1 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAY PY 1996 VL 27 IS 5 BP 1140 EP 1148 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA UJ747 UT WOS:A1996UJ74700016 PM 8621208 ER PT J AU Unser, M Thevenaz, P Aldroubi, A AF Unser, M Thevenaz, P Aldroubi, A TI Shift-orthogonal wavelet bases using splines (vol 3, pg 85, 1996) SO IEEE SIGNAL PROCESSING LETTERS LA English DT Correction, Addition RP Unser, M (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892, USA. RI Unser, Michael/A-1550-2008; Aldroubi, Akram/J-7186-2012 NR 1 TC 0 Z9 0 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 1070-9908 J9 IEEE SIGNAL PROC LET JI IEEE Signal Process. Lett. PD MAY PY 1996 VL 3 IS 5 BP 162 EP 162 DI 10.1109/LSP.1996.491662 PG 1 WC Engineering, Electrical & Electronic SC Engineering GA UK294 UT WOS:A1996UK29400010 ER PT J AU Wiest, DL Ashe, JM Abe, R Bolen, JB Singer, A AF Wiest, DL Ashe, JM Abe, R Bolen, JB Singer, A TI TCR activation of ZAP70 is impaired in CD4(+)CD8(+) thymocytes as a consequence of intrathymic interactions that diminish available p56(lck) SO IMMUNITY LA English DT Article ID T-CELL RECEPTOR; TYROSINE-PROTEIN-KINASE; IMMATURE CD4+CD8+ THYMOCYTES; ANTIGEN RECEPTOR; MICE LACKING; MONOCLONAL-ANTIBODY; ZETA-CHAIN; LYMPHOCYTES-T; CD8 LINEAGE; EXPRESSION AB The fate of developing CD4(+)CD8(+) thymocytes is determined by signals transduced through surface TCR complexes. Here, we report that cross-linking of TCR on CD4(+)CD8(+) thymocytes fails to activate ZAP70 protein tyrosine kinase and fails to initiate downstream signaling events, unless the TCR are coaggregated with surface coreceptor molecules. TCR signaling in CD4(+)CD8(+) thymocytes is impaired because the number of available p56(lck) molecules is diminished by intrathymic CD4-1a interactions that initially activate p56(lck) molecules, which are subsequently degraded. As a consequence of intrathymic CD4-1a interactions, TCR zeta chains are initially phosphorylated to recruit ZAP70 molecules, but the recruited ZAP70 molecules are not subsequently phosphorylated, resulting in TCR complexes that are stably associated with inactive ZAP70 molecules. Thus, intrathymic interactions that diminish p56(lck) regulate TCR signaling thresholds and affect TCR structure in developing CD4(+)CD8(+) thymocytes. C1 USN,MED RES INST,IMMUNE CELL BIOL DEPT,BETHESDA,MD 20889. DNAX RES INST MOLEC & CELLULAR BIOL INC,DEPT CELLULAR SIGNALING,PALO ALTO,CA 94304. RP Wiest, DL (reprint author), NCI,EXPTL IMMUNOL BRANCH,NIH,BLDG 10,BETHESDA,MD 20892, USA. OI Wiest, David/0000-0002-0792-3188 NR 56 TC 71 Z9 71 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 1996 VL 4 IS 5 BP 495 EP 504 DI 10.1016/S1074-7613(00)80415-X PG 10 WC Immunology SC Immunology GA UM678 UT WOS:A1996UM67800008 PM 8630734 ER PT J AU Shearer, WT Fleisher, TA AF Shearer, WT Fleisher, TA TI Organ and bone marrow transplantation - Preface SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 NIH,DEPT CLIN PATHOL,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892. RP Shearer, WT (reprint author), TEXAS CHILDRENS HOSP,BAYLOR COLL MED,6621 FANNIN ST,HOUSTON,TX 77030, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD MAY PY 1996 VL 16 IS 2 BP R11 EP R12 DI 10.1016/S0889-8561(05)70244-7 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA UL980 UT WOS:A1996UL98000001 ER PT J AU Rocken, M Racke, M Shevach, EM AF Rocken, M Racke, M Shevach, EM TI IL-4-induced immune deviation as antigen-specific therapy for inflammatory autoimmune disease SO IMMUNOLOGY TODAY LA English DT Article ID CD4+ T-CELLS; DIFFERENTIAL REGULATION; INTERFERON-GAMMA; FUNCTIONAL-PROPERTIES; LYMPHOKINE SECRETION; IL-4-PRODUCING CELLS; GENE-EXPRESSION; INTERLEUKIN-4; HELPER; IL-4 AB Organ-specific autoimmune diseases are mediated by interferon gamma (IFN-gamma)-producing T helper 1 (Th1) cells. Here, Martin Rocken and colleagues review the experimental basis for an antigen-specific therapeutic approach to inflammatory autoimmune diseases. This strategy involves selective deviation of harmful Th1 responses towards an anti-inflammatory, interleukin 4 (IL-4)-producing Th2 phenotype. C1 WASHINGTON UNIV,SCH MED,DEPT NEUROL & NEUROSURG,ST LOUIS,MO 63110. NIAID,IMMUNOL LAB,CELLULAR IMMUNOL SECT,BETHESDA,MD 20892. RP Rocken, M (reprint author), UNIV MUNICH,DEPT DERMATOL,FRAUENLOBSTR 9-11,D-80337 MUNICH,GERMANY. NR 80 TC 222 Z9 225 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD MAY PY 1996 VL 17 IS 5 BP 225 EP 231 DI 10.1016/0167-5699(96)80556-1 PG 7 WC Immunology SC Immunology GA UH633 UT WOS:A1996UH63300007 PM 8991384 ER PT J AU Hui, GSN Nikaido, C Hashiro, C Kaslow, DC Collins, WE AF Hui, GSN Nikaido, C Hashiro, C Kaslow, DC Collins, WE TI Dominance of conserved B-cell epitopes of the Plasmodium falciparum merozoite surface protein, MSP1, in blood-stage infections of naive Aotus monkeys SO INFECTION AND IMMUNITY LA English DT Article ID PROTECTIVE MONOCLONAL-ANTIBODY; CARBOXYL-TERMINAL FRAGMENT; IMMUNE-RESPONSE; PARASITE; ANTIGEN; RECOMBINANT; PRECURSOR; YOELII; GROWTH; GP195 AB We have shown that conserved B epitopes were immunodominant in animals hyperimmunized with parasite-purified or recombinant merozoite surface protein MSP1 of Plasmodium falciparum. Cross-priming studies also suggested that a conserved T-helper epitope(s) is efficient in inducing the anti-MSP1 antibody response. In this study, we determined whether a similar profile of immune responses was induced during live P. falciparum infections. Naive Aotus monkeys were infected by blood-stage challenge with either one of the two dimorphic MSP1 alleles represented by the FUP and FVO parasites. Sera collected after parasite clearance were analyzed by enzyme-linked immunosorbent assays (ELISAs). Monkeys infected with parasites carrying one allelic form of MSP1 had antibodies that were equally reactive with homologous or heterologous MSP1s. This preferential recognition of conserved epitopes of MSP1 was confirmed by competitive binding ELISAs. Studies with Plasmodium yoelii and P. falciparum show that the C-terminal 19-kDa fragment of MSP1, MSP1(19), is the target of protective immunity. Thus, monkey sera were assayed for recognition with recombinant MSP1(19)s expressing variant and conserved B epitopes. Results of direct and competitive binding ELISAs showed that the anti-MSP1(19) antibodies were also directed primarily against conserved determinants. The similarities between vaccine- or infection-induced antibody responses suggest a possible reciprocal enhancement of the two populations of anti-MSP1 antibodies when a subunit MSP1 vaccine is introduced into populations living in areas where malaria is endemic. This together with previous observations that conserved determinants are important in MSP1-mediated immunity provides an optimistic outlook that a subunit MSP1 vaccine may be effective and practical for field applications in malaria-exposed populations. C1 NIAID,MOL VACCINE SECT,MALARIA RES LAB,BETHESDA,MD. CTR DIS CONTROL & PREVENT,DIV PARASIT DIS,ATLANTA,GA 30341. RP Hui, GSN (reprint author), UNIV HAWAII,LEAHI HOSP,DEPT TROP MED,3675 KILAUEA AVE,HONOLULU,HI 96816, USA. FU NIAID NIH HHS [AI30589] NR 34 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1996 VL 64 IS 5 BP 1502 EP 1509 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UG365 UT WOS:A1996UG36500002 PM 8613353 ER PT J AU Gaydos, CA Summersgill, JT Sahney, NN Ramirez, JA Quinn, TC AF Gaydos, CA Summersgill, JT Sahney, NN Ramirez, JA Quinn, TC TI Replication of Chlamydia pneumoniae in vitro in human macrophages, endothelial cells, and aortic artery smooth muscle cells SO INFECTION AND IMMUNITY LA English DT Article ID STRAIN TWAR; ACQUIRED PNEUMONIA; INFECTION; DISEASE; BRONCHITIS; PSITTACI; CULTURE AB Chlamydia pneumoniae has recently been associated with atherosclerotic lesions in coronary arteries. To investigate the biological basis for the dissemination and proliferation of this organism in such lesions, the in vitro growth of C. pneumoniae was studied in two macrophage cell lines, peripheral blood monocyte-derived macrophages, human bronchoalveolar lavage macrophages, several endothelial cell lines, and aortic smooth muscle cells. Five strains of C. pneumoniae were capable of three passages in human U937 macrophages and in murine RAW 246.7 macrophages. Titers were suppressed in both macrophage types with each passage, as compared with growth titers in HEp-2 cells. Both human bronchoalveolar lavage macrophages and peripheral blood monocyte derived macrophages were able to inhibit C. pneumoniae after 96 h of growth. Eleven C. pneumoniae strains were capable of replicating in normal human aortic artery-derived endothelial cells, umbilical vein-derived endothelial cells, and pulmonary artery endothelial cells. Infection in human aortic artery smooth muscle cells was also established for 13 strains of C. pneumoniae. The in vitro ability of C. pneumoniae to maintain infections in macrophages, endothelial cells, and aortic smooth muscle cells may provide support for the hypothesis that C. pneumoniae can infect suck cells and, when infection is followed by an immune response, may contribute to atheroma formation in vivo. More studies are needed to investigate the complex relationship between lytic infection and persistence and the potential for C. pneumoniae to influence the generation of atheromatous lesions. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. UNIV LOUISVILLE,DEPT INFECT DIS,LOUISVILLE,KY 40292. RP Gaydos, CA (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV INFECT DIS,720 RUTLAND AVE,ROSS 1159,BALTIMORE,MD 21205, USA. RI Gaydos, Charlotte/E-9937-2010; Quinn, Thomas/A-2494-2010 NR 38 TC 366 Z9 383 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1996 VL 64 IS 5 BP 1614 EP 1620 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UG365 UT WOS:A1996UG36500018 PM 8613369 ER PT J AU Grassme, HUC Ireland, RM VanPutten, JPM AF Grassme, HUC Ireland, RM VanPutten, JPM TI Gonococcal opacity protein promotes bacterial entry-associated rearrangements of the epithelial cell actin cytoskeleton SO INFECTION AND IMMUNITY LA English DT Article ID RECEPTOR-MEDIATED ENDOCYTOSIS; TISSUE-CULTURE CELLS; NEISSERIA-GONORRHOEAE; CHLAMYDIA-TRACHOMATIS; SHIGELLA-FLEXNERI; PHASE VARIATION; GROWTH-FACTOR; HELA-CELLS; F-ACTIN; MEMBRANE AB Neisseria gonorrhoeae enters cultured human mucosal cells following binding of a distinct gonococcal opacity (Opa) outer membrane protein to cell surface proteoglycan receptors. We examined the route of internalization that is activated by Opa-expressing gonococci (strain VP1). Microscopy of infected Chang epithelial cells showed that gonococcal uptake was insensitive to monodansylcadaverine (150 mu M), which interferes with clathrin-mediated endocytosis. Similarly, indirect immunofluorescence staining for clathrin in infected cells showed distribution of cellular clathrin unaltered from the distribution in noninfected cells. The microtubule inhibitors colchicine (50 mu M) and nocodazole (20 mu M) but not the microtubule-stabilizing agent taxol (10 mu M) caused a moderate (30 to 50%) reduction in gonococcal entry without affecting bacterial adherence. The most dramatic effects were obtained with the microfilament-disrupting agent cytochalasin D (3 mu M), which totally blocked bacterial entry into the cells. Double immunofluorescence staining of gonococci and actin filaments in infected cells demonstrated bacterium-associated accumulations of F-actin as an early signal of bacterial entry. This recruitment of F-actin was transient and disappeared once the bacteria were inside the cells. Cytochalasin D disrupted the actin cytoskeleton architecture but did not prevent the recruitment of F-actin by the bacteria. Adherent, noninvasive gonococcal Opa variants lacked the ability to mobilize F-actin. Recombinant Escherichia coli expressing the gonococcal invasion-promoting Opa of gonococcal strain MS11 (Opa(50)) adhered to the epithelial cells in an Opa-dependent fashion but was not internalized and did not recruit detectable amounts of F-actin. Coinfection with the E. coli recombinant strain and gonococci resulted in specific entry of the diplococci, despite the presence of large numbers of adherent E. coli cells. Together, our results indicate that Opa-mediated gonococcal entry into Chang cells resembles phagocytosis rather than macropinocytosis reported for Salmonella spp. and sequentially involves gonococcal adherence to the cell surface, Opa-dependent and cytochalasin-insensitive recruitment of F-actin, and cytochalasin D-sensitive bacterial internalization. C1 NIAID,MICROBIAL STRUCT & FUNCT LAB,NIH,ROCKY MT LABS,HAMILTON,MT 59840. MAX PLANCK INST BIOL,INFEKT BIOL ABT,D-72076 TUBINGEN,GERMANY. OI van Putten, Jos/0000-0002-4126-8172 NR 54 TC 84 Z9 85 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1996 VL 64 IS 5 BP 1621 EP 1630 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UG365 UT WOS:A1996UG36500019 PM 8613370 ER PT J AU Theiss, P Karpas, A Wise, KS AF Theiss, P Karpas, A Wise, KS TI Antigenic topology of the P29 surface lipoprotein of Mycoplasma fermentans: Differential display of epitopes results in high-frequency phase variation SO INFECTION AND IMMUNITY LA English DT Article ID ESCHERICHIA-COLI; MOLECULAR-BASIS; PROTEINS; EXPRESSION; BACTERIA; FAMILY; GENES; SET AB Antibodies to P29, a major lipid-modified surface protein of Mycoplasma fermentans, reveal phase variation of surface epitopes occurring,vith high frequency in clonal lineages of the organism, This occurs despite continuous expression of the entire epitope-bearing P29 product (detected by Western immunoblotting) and contrasts with phase variation of other surface antigens mediated by differential expression of proteins. To understand the structure and antigenic topology of P29, the single-copy p29 gene from strain PG18 was cloned and sequenced. The gene encodes a prolipoprotein containing a signal sequence predicted to be modified with lipid and cleaved at the N-terminal Cys-1 residue of the mature P29 lipoprotein. The remaining 218-residue hydrophilic sequence of P29 is predicted to be located external to the single plasma membrane. Additional Cys residues at positions 91 and 128 in the mature protein were shown to form a 36-residue disulfide loop by selectively labeling sulfhydryl groups that were liberated only after chemical reduction of monomeric P29. Two nearly identical charged amino acid sequences occurred in P29, within the disulfide loop and upstream of this structure. Two distinct epitopes binding different monoclonal antibodies were associated with opposite ends of the P29 protein, by mapping products expressed in Escherichia coli from PCR-generated 3' deletion mutations of the p29 gene. Each monoclonal antibody detected high-frequency and noncoordinate changes in accessibility of the corresponding epitopes in colony immunoblots of clonal variants, yet sequencing of the p29 gene from these variants and analysis of disulfide bonds revealed no associated changes in the primary sequence or disulfide loop structure of P29. These results suggest that P29 surface epitope variation may involve masking of selected regions of P29, possibly by other surface components undergoing phase variation by differential expression, Differential masking may be an important mechanism for altering the antigenic or functional surface topology of this mycoplasma and other wall-less mycoplasmas. C1 UNIV MISSOURI,SCH MED,DEPT MOLEC MICROBIOL & IMMUNOL,COLUMBIA,MO 65212. NICHHD,BETHESDA,MD 20892. FU NIAID NIH HHS [AI32219, T32 AI07276] NR 45 TC 27 Z9 28 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1996 VL 64 IS 5 BP 1800 EP 1809 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UG365 UT WOS:A1996UG36500043 PM 8613394 ER PT J AU Konkel, ME Mead, DJ Cieplak, W AF Konkel, ME Mead, DJ Cieplak, W TI Cloning, sequencing, and expression of a gene from Campylobacter jejuni encoding a protein (Omp18) with similarity to peptidoglycan-associated lipoproteins SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE PROTEIN; INFLUENZAE TYPE-B; HEMOPHILUS-INFLUENZAE; NUCLEOTIDE-SEQUENCE; ESCHERICHIA-COLI; LEGIONELLA-PNEUMOPHILA; P6; IDENTIFICATION; PURIFICATION; ANTIBODY AB A Campylobacter jejuni genomic plasmid library was screened with antiserum generated against whole C. jejuni, revealing two immunoreactive clones. Sequence analysis of the recombinant plasmids revealed a common open reading frame of 498 nucleotides encoding a protein of 165 amino acids with a calculated molecular mass of 18,018 Da. The recombinant product partitioned to the outer membrane fractions of Escherichia coli transformants and has been designated Omp18. The deduced amino acid sequence of the cloned C. jejuni gene exhibits considerable similarity to peptidoglycan-associated lipoproteins from other gram-negative bacteria. C1 NIAID,INTRACELLULAR PARASITES LAB,ROCKY MT LABS,HAMILTON,MT 59840. RP Konkel, ME (reprint author), WASHINGTON STATE UNIV,DEPT MICROBIOL,PULLMAN,WA 99164, USA. NR 27 TC 16 Z9 16 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1996 VL 64 IS 5 BP 1850 EP 1853 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UG365 UT WOS:A1996UG36500051 PM 8613402 ER PT J AU Schooler, NR Severe, JB Glick, ID Hargreaves, WA Keith, SJ Weiden, P Matthews, SM Schultz, SC Odbert, CL Kane, JM Lieberman, JA Woerner, M Bellack, AS Simpson, GM Frances, AJ Jacobs, M Ninan, PT Mance, RM Falloon, IRH McGill, CW AF Schooler, NR Severe, JB Glick, ID Hargreaves, WA Keith, SJ Weiden, P Matthews, SM Schultz, SC Odbert, CL Kane, JM Lieberman, JA Woerner, M Bellack, AS Simpson, GM Frances, AJ Jacobs, M Ninan, PT Mance, RM Falloon, IRH McGill, CW TI Transition from acute to maintenance treatment: Prediction of stabilization SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT Lundbeck Symposium on the Acute Episode in Schizophrenia - Diagnosis, Prognosis and Treatment CY FEB 09-10, 1996 CL COPENHAGEN, DENMARK DE schizophrenia; acute treatment; maintenance medication; fluphenazine decanoate; dosage ID SCHIZOPHRENIA AB The stabilization period that follows the exacerbation of a schizophrenic illness represents a critical point in the course of the illness. Successful stabilization is a prerequisite to long-term tenure in the community and the possibility of improvement in functional outcome. In this paper we present an operational definition of stabilization developed in the context of a study of long-term maintenance treatment that incorporates time, symptomatic equilibrium and consistency of medication dosage. Patients were identified at the time of hospitalization and followed prospectively to determine whether or not they met stabilization criteria. Characteristics that predicted successful stabilization included measures drawn from the domains of patient personal characteristics and psychiatric history, symptoms of psychopathology and side effects in response to initial treatment and family judgments. These patients were treated primarily with fluphenazine decanoate, and five distinct dosing strategies with this agent were identified retrospectively. The dosing strategies distinguished the length of time to subsequent stabilization. The implications of these findings for clinical management of schizophrenia are discussed. C1 UNIV PITTSBURGH,MED CTR,DEPT PSYCHIAT,PITTSBURGH,PA. NIMH,ROCKVILLE,MD 20857. STANFORD UNIV,DEPT PSYCHIAT & BEHAV SCI,PALO ALTO,CA 94304. UNIV CALIF SAN FRANCISCO,DEPT PSYCHIAT,SAN FRANCISCO,CA 94143. UNIV NEW MEXICO,DEPT PSYCHIAT,ALBUQUERQUE,NM 87131. ST LUKES ROOSEVELT HOSP,DEPT PSYCHIAT,NEW YORK,NY 10025. RP Schooler, NR (reprint author), WESTERN PSYCHIAT INST & CLIN,3811 OHARA ST,PITTSBURGH,PA 15213, USA. FU NIMH NIH HHS [UO1 MH39998, UO1 MH39992, UO1 MH40007] NR 12 TC 5 Z9 5 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD MAY PY 1996 VL 11 SU 2 BP 85 EP 91 DI 10.1097/00004850-199605002-00014 PG 7 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA UR527 UT WOS:A1996UR52700014 PM 8803666 ER PT J AU AlexanderMiller, MA Parker, KC Tsukui, T Pendleton, CD Coligan, JE Berzofsky, JA AF AlexanderMiller, MA Parker, KC Tsukui, T Pendleton, CD Coligan, JE Berzofsky, JA TI Molecular analysis of presentation by HLA-A2.1 of a promiscuously binding V3 loop peptide from the HIV-1 envelope protein to human cytotoxic T lymphocytes SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE antigen presentation; cytotoxic T lymphocyte; MHC-peptide interaction ID IMMUNODEFICIENCY-VIRUS ENVELOPE; CLASS-I MOLECULES; CELL EPITOPES; RECOGNITION; GP160; DETERMINANT; MOTIF; VACCINATION; INDIVIDUALS; PREDICTION AB P18(IIIB) is a highly immunogenic peptide from the V3 loop of the HIV-1 gp160 envelope protein that is presented promiscuously by multiple class I MHC molecules, Understanding the molecular basis for promiscuous presentation may have many practical applications, As the highly prevalent HLA-A2.1 class I molecule is known to present P18(IIIB) for recognition by cytotoxic T lymphocytes (CTL) found in peripheral blood mononuclear cells of HIV+ donors, a P18(IIIB)-specific CTL line was generated from an HLA-A2(+), HIV- donor in order to define the molecular basis for, and ultimately improve upon the binding of, this peptide to HLA-A2.1. The minimal epitope recognized by the line was a decamer, I10, with the sequence RGPGRAFVTI. Interestingly, this decamer is identical to the minimal epitope from P18(IIIB) seen by murine CTL restricted by H-2D(d), A panel of Ala-substituted peptides was employed in MHC-binding and T cell response studies to identify MHC- and TCR-binding residues, Notably, many of the agretopic and epitopic residues identified were identical to those involved in the corresponding interactions of I10 with the H-2D(d) MHC molecule and murine Il0-specific CTL, The I10 peptide does not contain the described HLA-A2.1 binding motif. instead a Pro at P3, a Phe at P7 and an Ile at P10 are utilized for MHC binding, Agretopic residue similarities with the hepatitis a nucleocapsid decamer suggest that these residues may comprise an alternative motif of anchors utilized by decamers for binding to HLA-A2.1. C1 NCI,METAB BRANCH,NIH,BETHESDA,MD 20892. NIAID,NCI,MOLEC STRUCT LAB,BETHESDA,MD 20892. OI Parker, Kenneth/0000-0002-6282-2478 NR 35 TC 34 Z9 34 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAY PY 1996 VL 8 IS 5 BP 641 EP 649 DI 10.1093/intimm/8.5.641 PG 9 WC Immunology SC Immunology GA UN188 UT WOS:A1996UN18800002 PM 8671651 ER PT J AU Shparago, N Zelazowski, P Jin, L McIntyre, TM Stuber, E Pecanha, LMT Kehry, MR Mond, JJ Max, EE Snapper, CM AF Shparago, N Zelazowski, P Jin, L McIntyre, TM Stuber, E Pecanha, LMT Kehry, MR Mond, JJ Max, EE Snapper, CM TI IL-10 selectively regulates murine Ig isotype switching SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE anti-Ig-dextran; CD40; CD40 ligand; digestion-circularization PCR; IL-4; IL-5; lipopolysaccharide; transforming growth factor-beta ID HUMAN B-CELLS; CYTOKINE PRODUCTION; IMMUNOGLOBULIN-A; LYMPHOCYTES-B; INTERLEUKIN-10; TRANSCRIPTS; ANTIBODY; GROWTH; RECOMBINATION; EXPRESSION AB A role for IL-10 in regulating Ig isotype switching directly at the level of the murine B cell has not been previously reported, In this report we show that IL-10 selectively up-regulated IgM to IgG3 class switching in lipopolysaccharide (LPS)-activated cultures through a direct effect on membrane (m) IgM(+)IgG3(-) B cells in vitro. IL-10 stimulated a 3- to 4-fold enhancement (from 6-8 to 20-30%) in membrane mIgG3(+) cells and a significant increase in S-mu-S(gamma)3 DNA rearrangement events as measured by digestion-circularization PCR (DC-PCR) over that observed with LPS alone, IL-10 induction of switching to lgG3 was not accompanied by a corresponding increase in the steady-state levels of germline C(H gamma)3 RNA, By contrast, IL-10 strongly inhibited the transforming growth factor-beta-mediated generation of mIgA(+) cells and S-mu-S-alpha DNA rearrangement events in LPS-, but not CD40 ligand (CD40L)-activated B cells, This effect was not accompanied by changes in the steady-state levels of germline C-H alpha RNA. IL-10 had no effect on IL-4-mediated switching to either IgG1 or IgE in either LPS- or CD40L-activated B cells, Thus, IL-10 can either enhance or suppress switching to particular murine Ig isotypes but it differs from most other murine cytokines in that its effects on switching do not appear to be associated with changes in the corresponding steady-state levels of germline C-H RNA. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PATHOL,BETHESDA,MD 20814. UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. NIH,CLIN INVEST LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. IM UFRJ,DEPTO IMUNOL,RIO JANEIRO,BRAZIL. BOEHRINGER INGELHEIM PHARMACEUT INC,RIDGEFIELD,CT 06877. FU NIAID NIH HHS [AI32560, AI36588] NR 40 TC 35 Z9 35 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAY PY 1996 VL 8 IS 5 BP 781 EP 790 DI 10.1093/intimm/8.5.781 PG 10 WC Immunology SC Immunology GA UN188 UT WOS:A1996UN18800018 PM 8671667 ER PT J AU Hanson, RL Jacobsson, LTH McCance, DR Narayan, KMV Pettitt, DJ Bennett, PH Knowler, WC AF Hanson, RL Jacobsson, LTH McCance, DR Narayan, KMV Pettitt, DJ Bennett, PH Knowler, WC TI Weight fluctuation, mortality and vascular disease in Pima Indians SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE mortality; vascular disease; weight cycling; weight fluctuation ID BODY-WEIGHT; DIABETES-MELLITUS; FOLLOW-UP; MEN; OBESITY; VARIABILITY; WOMEN; RISK; PROTEINURIA; PREVALENCE AB OBJECTIVE: To examine the relationship of weight fluctuation to mortality rates and incidence of vascular disease. SUBJECTS: A cohort of Pima Indians, 572 of whom had non-insulin-dependent diabetes mellitus and 766 without diabetes. DESIGN: Individuals were invited biennially to research examinations, The root mean square error (RMSE) of the linear trend of weight with time for the first four examinations after age 20 years was used as an index of weight fluctuation. Subjects were followed from the fourth examination until death or until 31 December 1991. The mortality rate ratio (MRR) and its 95% confidence interval (CI) for those with a high weight fluctuation index relative to those with a lower value were determined. The median duration of follow up was 9.3 (range 0.1-22.6) years. MEASUREMENTS: All cause mortality (n = 356); incidence of diabetic retinopathy (n = 145), diabetic nephropathy (n = 132) and electrocardiographic abnormalities (n = 82). RESULTS: There was no significant relationship between weight fluctuation and mortality for diabetic subjects (MRR = 1.0, 95% CI 0.8-1.3, p = 0.91). Nondiabetic subjects with a high weight fluctuation index had a higher mortality rate than those with a lower index (MRR = 1.5, 95% CI 1.0-2.1. p = 0.03); the association was stronger among men than among women, The excess mortality in the high weight fluctuation group was not due to cardiovascular diseases, but to noncardiovascular causes and the risk for alcohol-related death was particularly increased, Weight fluctuation was not associated with the incidence of diabetic retinopathy, nephropathy or electrocardiographic abnormalities. CONCLUSIONS: A high weight fluctuation index was associated with higher mortality rates in nondiabetic, but not in diabetic, Pima Indians. The excess mortality is largely due to noncardiovascular causes of death and may reflect lifestyle factors associated with weight fluctuation, rather than its metabolic effects. C1 NIAMSD,PHOENIX,AZ 85014. RP Hanson, RL (reprint author), NIDDKD,DIABET & ARTHRIT EPIDEMIOL SECT,1550 E INDIAN SCH RD,PHOENIX,AZ 85014, USA. RI Narayan, K.M. Venkat /J-9819-2012; Hanson, Robert/O-3238-2015 OI Narayan, K.M. Venkat /0000-0001-8621-5405; Hanson, Robert/0000-0002-4252-7068 NR 49 TC 7 Z9 7 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD MAY PY 1996 VL 20 IS 5 BP 463 EP 471 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA UH736 UT WOS:A1996UH73600011 PM 8696426 ER PT J AU Bhat, NK Fischinger, PJ Seth, A Watson, DK Papas, T AF Bhat, NK Fischinger, PJ Seth, A Watson, DK Papas, T TI Pleiotropic functions of ETS-1 (Review) SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE ETS family of genes; transcription factor; ETS target genes; signal transduction; apoptosis; lymphoid cell development ID C-ETS-1 PROTOONCOGENE; TRANSCRIPTION FACTORS; PROMOTER; GENE; EXPRESSION; FAMILY; DOMAIN; CELLS AB ETS-1 is a cellular homologue of the viral ets oncogene of the E26 virus and functions as a sequence specific transcription factor. It plays an important role in cell proliferation, differentiation, lymphoid cell development, transformation, angiogenesis and apoptosis. ETS-1 may control the expression of critical genes involved in these processes by binding to ets binding sites present in their transcriptional regulatory regions. Recent progress in understanding the multiple functions of ETS-1 is summarized in this review. C1 WOMENS COLL HOSP,TORONTO,ON,CANADA. UNIV TORONTO,MRC GRP,TORONTO,ON M5S 1A1,CANADA. MED UNIV S CAROLINA,HOLLINGS CANC CTR,CTR MOL & STRUCT BIOL,CHARLESTON,SC 29425. RP Bhat, NK (reprint author), NCI,SCI APPLICAT INT CORP,FREDERICK CANC RES & DEV CTR,POB B,FREDERICK,MD 21702, USA. NR 44 TC 19 Z9 19 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAY PY 1996 VL 8 IS 5 BP 841 EP 846 PG 6 WC Oncology SC Oncology GA UF761 UT WOS:A1996UF76100001 PM 21544435 ER PT J AU Liebmann, J Herscher, L Fisher, J Teague, D Cook, JA AF Liebmann, J Herscher, L Fisher, J Teague, D Cook, JA TI Antagonism of paclitaxel cytotoxicity by X-rays: Implications for the sequence of combined modality therapy SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE paclitaxel; X-ray irradiation; combined modality therapy ID RADIATION SENSITIZER; CELL LINES; TAXOL; AGENT; MECHANISM; PROTEIN; CANCER; CYCLE AB We have employed in vitro clonogenic assays and DNA flow cytometry to examine the effect of X-ray irradiation on the response of human tumor cells to paclitaxel. Irradiation caused the development of cell cycle delays in G1 and G2/M in the human breast MCF-7 and lung A549 adenocarcinoma cell lines. Irradiation given just prior to or concurrently with exposure to paclitaxel reduced cytotoxicity due to paclitaxel. For example, the surviving fraction of both MCF-7 and A549 cells was 0.03 after 24 h of exposure to 50 nM paclitaxel. However, if the cells were irradiated with 3 Gy just prior to the start of 24 h of paclitaxel exposure, the surviving fractions of MCF-7 and A549 cells were 0.08. Since 3 Gy alone reduced the survival of MCF-7 and A549 cells by 65% and 50%, respectively, the surviving fractions of MCF-7 and A549 cells were 7.6 and 5.3 fold higher after treatment with radiation and paclitaxel than would have been predicted if the cytotoxicities of the different treatments had been additive. Incubation of cells in 5 mM pentoxifylline after irradiation reduced the G2/M block induced by radiation and partially reversed the antagonism of paclitaxel cytotoxicity. These data show that radiation, by inducing cell cycle delays, can antagonize the cytotoxicity of paclitaxel. These results have implications for the development of clinical protocols which combine radiation and paclitaxel in treatment plans. C1 NCI,RADIAT BIOL BRANCH,BETHESDA,MD 20892. NR 31 TC 17 Z9 18 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAY PY 1996 VL 8 IS 5 BP 991 EP 996 PG 6 WC Oncology SC Oncology GA UF761 UT WOS:A1996UF76100022 PM 21544456 ER PT J AU Amundson, SA Chen, DJ AF Amundson, SA Chen, DJ TI Inverse dose-rate effect for mutation induction by gamma-rays in human lymphoblasts SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article ID DIPLOID HUMAN-LYMPHOBLASTS; IONIZING-RADIATION; HUMAN-CELLS; X-RAYS; ONCOGENIC TRANSFORMATION; TRITIATED-WATER; L5178Y CELLS; CHO CELLS; DNA; NEUTRONS AB In order to define further the effects of differences in recombinational proficiency on cell survival and mutation by ionizing radiation, we exposed the syngenic cell lines TK6 and WTK1 to continuous low dose-rate gamma-irradiation. We previously demonstrated that acute X-ray exposure results in lower survival and lower mutation induction at both the thymidine kinase (tk) and the hypoxanthine-guanine phosphoribosyltransferase (hprt) loci in TK6 cells compared with WTK1 cells. These differences were attributed in part to reduced levels of recombination in the TK6 line relative to WTK1. Using a low dose rate Cs-137 irradiator, we exposed asynchronous growing populations of these cells to gamma-rays at 14.3, 6.7 and 2.7 cCy/h. Both cell lines exhibited a dose-rate effect on survival. Compared with acute doses, the low dose-rates also protected against mutation induction at the hrpt locus in WTK1, but protection was inversely related to dose-rate. There was also a slight inverse dose-rate effect in TK6, with mutation induction at the lowest dose-rate exceeding that at acute exposures. C1 LOS ALAMOS NATL LAB,DIV LIFE SCI LS6,LOS ALAMOS,NM. RP Amundson, SA (reprint author), NCI,MOLEC PHARMACOL LAB,NIH,37 CONVENT DR,BLDG 37,RM 5D02,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA56414] NR 43 TC 27 Z9 31 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD MAY PY 1996 VL 69 IS 5 BP 555 EP 563 DI 10.1080/095530096145562 PG 9 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA UP361 UT WOS:A1996UP36100004 PM 8648243 ER PT J AU Robison, WG Laver, NM Jacot, JL Glover, JP Basso, MD Blouin, P Hohman, TC AF Robison, WG Laver, NM Jacot, JL Glover, JP Basso, MD Blouin, P Hohman, TC TI Diabetic-like retinopathy ameliorated with the aldose reductase inhibitor WAY-121,509 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE aldose reductase; computer morphometry; diabetic retinopathy; galactose-fed rat model; polyol pathway ID RETINAL CAPILLARIES; RATS; PREVENTION; TOLRESTAT; MONOSACCHARIDES; CATARACT AB Purpose. To evaluate the efficacy of WAY-121,509, a potent new aldose reductase inhibitor (ARI), in preventing the retinopathy that develops in the galactose-fed rat model of diabetic ocular complications. Methods. Sprague-Dawley rats were randomized into treatment and duration groups and fed diets with either 50% starch or 50% galactose with or without WAY-121,509 (25 mg/kg body weight per day). Progression of cataracts was monitored by slit-lamp biomicroscopy. After durations of 4, 8, 16, and 24 months, levels of plasma glucose and glycated hemoglobin, as well as erythrocyte and retinal galactose and galactitol, were measured in rats of each group. Retinal vasculatures of the 24-month rats were isolated by elastase digestion and analyzed by computer-assisted morphometry. Results. Mature, diabetic-like cataracts developed within 5 weeks in all the galactose-fed, untreated rats, but only nonprogressive anterior cortical opacities were present in lenses of 85% of the ARI-treated galactosemic animals after 3 months. Plasma glucose remained the same in all groups. Erythrocyte and retinal galactose and glycated (galactosylated) hemoglobin were elevated with galactosemia and were unaffected by ARI treatment. Erythrocyte and retinal galactitol levels were decreased by 91% and 95%, respectively, with inhibitor treatment. At 24 months, capillary length, width, density, the number of microaneurysms, and the percent of capillary length involved in intraretinal microvascular abnormalities, expressed as hypercellular channels with diameters >20 mu m, were significantly increased by galactosemia and were attenuated in the galactose-fed, ARI-treated group. Conclusions. A dose of WAY-121,509 sufficient to reduce retinal polyol levels by 95% ameliorated the development of galactose-induced cataracts and diabetic-like retinopathy but was insufficient to prevent early lens opacifications or all the diabetic-like retinal microangiopathies. C1 GEORGETOWN UNIV,SCH MED,WASHINGTON,DC. WYETH AYERST RES,LABS,PRINCETON,NJ 08543. RP Robison, WG (reprint author), NEI,9000 ROCKVILLE PIKE,BLDG 6,ROOM 316,BETHESDA,MD 20892, USA. NR 37 TC 32 Z9 32 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 1996 VL 37 IS 6 BP 1149 EP 1156 PG 8 WC Ophthalmology SC Ophthalmology GA UK690 UT WOS:A1996UK69000021 PM 8631629 ER PT J AU Alberti, G Oguni, M Podgor, M Sperduto, RD Tomarev, S Grassi, C Williams, S KaiserKupfer, M Maraini, G Hejtmancik, JF AF Alberti, G Oguni, M Podgor, M Sperduto, RD Tomarev, S Grassi, C Williams, S KaiserKupfer, M Maraini, G Hejtmancik, JF TI Glutathione S-transferase M1 genotype and age-related cataracts lack of association in an Italian population SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE cataract risk factors; epidemiology; genetic diseases; glutathione; GSTM1; lens opacity; lens senescence; oxidative damage; transparency ID POLYMERASE CHAIN-REACTION; GST1 GENE DELETION; LUNG-CANCER; HYDROGEN-PEROXIDE; CLASS-MU; SUSCEPTIBILITY; JAPANESE; POLYMORPHISMS; LENSES; LOCUS AB Purpose. To investigate possible associations between the gene number and allelic forms of glutathione S-transferase M1 (GSTM1) and the occurrence of nuclear and cortical age-related cataracts. Methods. Patients with cortical cataract, nuclear cataract, mixed nuclear and cortical cataract, and no cataract were systematically selected from subjects evaluated in the Italian-American Study of the Natural History of Age-Related Cataract. The patients were typed for the A, B, and null alleles of GSTM1 using a variation of the amplification refractory mutation system. Results. Forty-nine percent of patients (50/102) with cortical cataracts, 45% (13/29) with nuclear cataracts, 51% (36/71) with mixed nuclear and cortical cataracts, and 50% of controls (49/98) were homozygous for the null GSTM1 allele. Twenty-five percent of patients (26/102) with cortical cataracts, 24% (7/29) with nuclear cataracts, 31% with mixed nuclear and cortical cataracts, and 21% of controls (26/98) displayed only the A allele for GSTM1. Twenty-four percent of patients (24/102) with cortical cataract, 24% (7/29) with nuclear cataracts, 14% (10/71) with mixed nuclear and cortical cataracts, and 18% of controls showed only the B allele for GSTM1. Two percent of patients (2/102) with cortical cataracts, 7% (2/29) with nuclear cataracts, 4% (3/71) with mixed nuclear and cortical cataracts, and 5% of controls (5/98) showed both A and B alleles for GSTM1. Conclusions. No associations between the GSTM1 alleles, including the null allele, and cataracts were detected in this study. C1 NEI,OGCSB,NIH,BETHESDA,MD 20892. NEI,DBE,NIH,BETHESDA,MD 20892. NEI,LMDB,NIH,BETHESDA,MD 20892. UNIV PARMA,INST OPHTHALMOL,I-43100 PARMA,ITALY. NR 37 TC 29 Z9 29 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 1996 VL 37 IS 6 BP 1167 EP 1173 PG 7 WC Ophthalmology SC Ophthalmology GA UK690 UT WOS:A1996UK69000023 PM 8631631 ER PT J AU OShaughnessy, JA AF OShaughnessy, JA TI Chemoprevention of breast cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID TAMOXIFEN TREATMENT; ADJUVANT TAMOXIFEN; CARCINOMA INSITU; RISK; EXPRESSION; RECEPTOR; TUMORS; WOMEN; TRIAL; RAT RP OShaughnessy, JA (reprint author), NCI,MED BRANCH,NATL INST HLTH,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 50 TC 25 Z9 25 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 1 PY 1996 VL 275 IS 17 BP 1349 EP 1353 DI 10.1001/jama.275.17.1349 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA UG612 UT WOS:A1996UG61200033 PM 8614122 ER PT J AU Young, MA Fogg, LF Scheftner, W Fawcett, J Akiskal, H Maser, J AF Young, MA Fogg, LF Scheftner, W Fawcett, J Akiskal, H Maser, J TI Stable trait components of hopelessness: Baseline and sensitivity to depression SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID SUICIDAL IDEATION; AFFECTIVE-DISORDERS; CONTENT-SPECIFICITY; EVENTUAL SUICIDE; SCALE; RELIABILITY; PREDICTORS; BEHAVIOR; GENDER; STYLE AB Hopelessness (H) plays an important theoretical and practical role in depression. The authors hypothesized that a patient's H is comprised of(a) a baseline level of H when not depressed and (b) an increment in H related to the severity of depression at the time and the person's rate of increase in H as a function of severity of depression (sensitivity). Baseline and sensitivity are explanatory stable traits; H and depression are observed, time-varying states. The corresponding statistical model described well the longitudinal data of 316 participants. Baseline and sensitivity were uncorrelated and correlated with different clinical and demographic variables. Baseline predicted a future suicide attempt; sensitivity and H when depressed did not. It may be useful to ask ''How hopeless is this person when not depressed and how much more hopeless is he or she when depressed?'': rather than simply ''How hopeless is this depressed person?'' C1 RUSH PRESBYTERIAN ST LUKES MED CTR,DEPT PSYCHOL,CHICAGO,IL 60612. NIMH,MOOD ANXIETY & PERSONAL DISORDERS BRANCH,ROCKVILLE,MD 20857. RP Young, MA (reprint author), RUSH PRESBYTERIAN ST LUKES MED CTR,DEPT PSYCHIAT,1725 W HARRISON ST,SUITE 955,CHICAGO,IL 60612, USA. NR 55 TC 92 Z9 94 U1 5 U2 8 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD MAY PY 1996 VL 105 IS 2 BP 155 EP 165 PG 11 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA UG905 UT WOS:A1996UG90500001 PM 8722997 ER PT J AU Derse, D Mikovits, J Waters, D Brining, S Ruscetti, F AF Derse, D Mikovits, J Waters, D Brining, S Ruscetti, F TI Examining the molecular genetics of HTLV-I with an infectious molecular clone of the virus and permissive cell culture systems SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE human T cell leukemia virus; retrovirus; T cell; molecular biology ID TROPICAL SPASTIC PARAPARESIS; COMPLETE NUCLEOTIDE-SEQUENCE; HUMAN-ENDOTHELIAL CELLS; LEUKEMIA-VIRUS; TRANSCRIPTIONAL ACTIVATOR; SURFACE PHENOTYPE; PERIPHERAL-BLOOD; LYMPHOMA VIRUS; PX REGION; EXPRESSION AB Infectious molecular clones of HTLV-I proviruses have only recently been reported. The long wait for such provirus clones reflects the difficulties inherent in propagating HTLV-I in vitro, and thus a rigorous demonstration of infectivity has awaited improved cell culture systems and sensitive detection techniques for HTLV-I. An intact HTLV-I provirus, originating from an American ATL patient, was subcloned into a plasmid vector and was designated pCS-HTLV. Transient transfections of mammalian cells with pCS-HTLV resulted in the synthesis of viral proteins and mRNAs which were assembled into virions that had physical and morphological characteristics typical of HTLV-I particles. The ability of these virus particles to infect cells, replicate, and produce infectious progeny was demonstrated initially in short term, cell-free infection assays by monitoring the expression of specific viral mRNAs. These studies have been extended in cell culture systems that support continuous virus production. Primary T-lymphocytes have been infected either with cell-free supernatant fluids from, or by coculture with, cells transiently transfected with pCS-HTLV, giving rise to continuous, IL-2-dependent cell lines that have been in culture for >1 year. Furthermore, fetal rhesus lung cells (FRhL) were shown to be permissive for HTLV-I replication and sustained virus expression after infection with pCS-HTLV. Continuous FRhL cell lines now have been established that express various HTLV-I proviruses and mutants. These provirus clones and cell lines provide us with the means to address long-standing questions dealing with the biology of HTLV-I. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,AIDS VACCINE DEV PROGRAM,FREDERICK,MD. RP Derse, D (reprint author), NCI,LAB LEUKOCYTE BIOL,FREDERICK,MD 21702, USA. NR 36 TC 24 Z9 24 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD MAY 1 PY 1996 VL 12 IS 1 BP 1 EP 5 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UK146 UT WOS:A1996UK14600001 PM 8624755 ER PT J AU Santelli, J Kouzis, A Newcomer, S AF Santelli, J Kouzis, A Newcomer, S TI Student attitudes toward school-based health centers SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE school-based health centers; attitudes; enrollment; confidentiality ID CLINICS; ADOLESCENTS; CARE AB Purpose: Little is known about student attitudes toward school-based health centers (SBHCs) or about factors that influence SBHC enrollment. Methods: Students in 9 Baltimore schools with SBHCs and 4 schools without health centers were surveyed in May 1991, using an anonymous classroom questionnaire. SBHC enrollees, nonenrollees from health center schools, and students in schools without health centers were compared using bi-variate analyses. Logistic regression analyses identified predictors of enrollment. Results: A total of 91% of enrollees supported having a SBHC compared with 89% of nonenrollees and 77% of students from non-health center schools (p < .001). Support for a variety of sen ices (including contraceptive services) was significantly higher among enrollees and nonenrollees compared with students in non-SBHC schools. A total of 86% of enrollees rated the quality of care ''satisfactory'' to ''excellent'' and 79% rated privacy in the school health center as ''satisfactory'' to ''excellent.'' The most common reason given for not enrolling was satisfaction with current provider. Independent predictors of student confidence in the privacy of SBHCs included prior SBHC use and enrollment of close peers. Predictors of enrollment included: one or more self-reported health problems; having medical assistance; attending one or more special education classes; enrollment of close peers; membership in a school club, sports team, or church organization; and being African-American. Conclusions: Students overwhelmingly supported school-based health centers. Personal experience and peer influences were important in shaping student attitudes. We found evidence of a ''learning curve'' gradient in student attitudes such that students with the greatest exposure to SBHCs (as measured by attending a SBHC school, enrolling in the SBHC, and using the health center) had the most favorable attitudes. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD. BALTIMORE CITY DEPT HLTH,BALTIMORE,MD. NICHHD,DEMOG & BEHAV SCI BRANCH,BALTIMORE,MD. NR 22 TC 21 Z9 21 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD MAY PY 1996 VL 18 IS 5 BP 349 EP 356 DI 10.1016/1054-139X(95)00226-I PG 8 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA UL119 UT WOS:A1996UL11900008 PM 9156548 ER PT J AU Huestis, MA Cone, EJ AF Huestis, MA Cone, EJ TI Marijuana detection times: Does the methodology validate the conclusions? Reply SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Letter RP Huestis, MA (reprint author), NIDA,ADDICT RES CTR,NIH,LEXINGTON,KY 40583, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD MAY-JUN PY 1996 VL 20 IS 3 BP 205 EP 206 PG 2 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA UK810 UT WOS:A1996UK81000014 ER PT J AU Irwin, RD Eustis, SL Stefanski, S Haseman, JK AF Irwin, RD Eustis, SL Stefanski, S Haseman, JK TI Carcinogenicity of glycidol in F344 rats and B6C3F mice SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article ID ETHYLENE-OXIDE; STATISTICAL ISSUES; PROPYLENE-OXIDE; BRAIN-TUMORS; DNA ADDUCTS; 7-(2-HYDROXYETHYL)GUANINE; INHALATION; EXPOSURES; ACROLEIN; TESTS AB Glycidol, a simple aliphatic epoxide, was administered by gavage in water to groups of male and female F344/N rats and B6C3F(1) mice, Rats received 0, 37.5 or 75 mg kg(-1) and mice received 0, 25 or 50 mg kg(-1) daily, 5 days per week for 2 years, Exposure to glycidol was associated with dose-related increases in the incidences of neoplasms in numerous tissues in both rats and mice, Survival of rats that received glycidol was markedly reduced compared to the control because of the early induction of neoplastic disease, In male rats, mesothelioma arising in the tunica vaginalis and frequently metastasizing to the peritoneum were considered the major cause of early death, Early deaths in female rats were associated with mammary gland neoplasms, Survival of female mice that received 50 mg kg(-1) was lower than the control after week 101 due primarily to euthanasia of moribund animals with mammary gland neoplasms, Survival of male mice and female mice that received 25 mg kg(-1) was comparable to the control, In mice, exposure to glycidol was associated with increased incidences of neoplasms of the harderian gland in males and females, the forestomach in males and the mammary gland in females. RP Irwin, RD (reprint author), NATL INST ENVIRONM HLTH SCI,RES TRIANGLE PK,NC, USA. NR 27 TC 18 Z9 19 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD MAY-JUN PY 1996 VL 16 IS 3 BP 201 EP 209 DI 10.1002/(SICI)1099-1263(199605)16:3<201::AID-JAT333>3.0.CO;2-0 PG 9 WC Toxicology SC Toxicology GA UW503 UT WOS:A1996UW50300003 PM 8818859 ER PT J AU Szekeres, ES Woodgate, R Lawrence, CW AF Szekeres, ES Woodgate, R Lawrence, CW TI Substitution of mucAB or rumAB for umuDC alters the relative frequencies of the two classes of mutations induced by a site-specific T-T cyclobutane dimer and the efficiency of translesion DNA synthesis SO JOURNAL OF BACTERIOLOGY LA English DT Article ID POLYMERASE-III HOLOENZYME; SINGLE-STRANDED VECTOR; ESCHERICHIA-COLI; RECA PROTEIN; INDUCED MUTAGENESIS; UV-MUTAGENESIS; ULTRAVIOLET-LIGHT; SOS MUTAGENESIS; REPAIR; CLEAVAGE AB We have examined the effect of replacing umuDC with mucAB or rumAB on the mutagenic properties of a T-T cyclobutane dimer in an attempt to determine the molecular basis for the differences in UV-induced mutagenesis that are associated with these structurally and functionally related genes. A single-stranded vector carrying a site-specific T-T cis-syn cyclobutane dimer was transfected into a set of isogenic Escherichia coli Delta umuDC strains harboring low-copy-number plasmids expressing UmuDC, MucAB, RumAB, or their genetically engineered and mutagenically active counterparts UmuD'C, MucA'B, and RumA', respectively. Although the overall mutation frequency was similar for all strains, the relative frequencies of the two classes of mutation induced by the T-T dimer varied according to the mutagenesis operon expressed. In umuDC strains, 3' T-->A mutations outnumbered 3' T-->C mutations, but the reverse was true for the mucAB and rumAB strains. We also found that the T-T dimer was bypassed with differing efficiencies in unirradiated. cells expressing wild-type UmuDC, MucAB, and RumAB proteins. These differences can probably be attributed to the relative efficiency of the normal cellular posttranslational activation of UmuD, MucA and RumA, respectively, Since recombinant constructs. expressing the mutagenically active UmuD'C, MucA'B, and RumA'B proteins all promoted similarly high levels of bypass in UV-irradiated cells. These results suggest that the UmuD'/UmuC complex and its homologs may differ in their relative abilities to promote elongation from T . T and T . G mismatched termini, Alternatively, they may differentially influence the efficiency with which these mismatches are edited or influence nucleotide insertion by the catalytic subunit of tbe DNA polymerase III. C1 UNIV ROCHESTER, MED CTR, DEPT BIOPHYS, SCH MED & DENT, ROCHESTER, NY 14642 USA. NICHHD, SECT DNA REPLICAT REPAIR & MUTAGENESIS, BETHESDA, MD 20892 USA. FU NIGMS NIH HHS [GM32885] NR 41 TC 38 Z9 38 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 1996 VL 178 IS 9 BP 2559 EP 2563 PG 5 WC Microbiology SC Microbiology GA UJ122 UT WOS:A1996UJ12200012 PM 8626322 ER PT J AU Balasundaram, D Tabor, CW Tabor, H AF Balasundaram, D Tabor, CW Tabor, H TI Sensitivity of polyamine-deficient Saccharomyces cerevisiae to elevated temperatures SO JOURNAL OF BACTERIOLOGY LA English DT Article ID S-ADENOSYLMETHIONINE DECARBOXYLASE; ALPHA-DIFLUOROMETHYLORNITHINE; ORNITHINE DECARBOXYLASE; SPERMIDINE; HEAT; SENSITIZATION AB Saccharomyces cerevisiae cells that cannot synthesize spermidine or spermine because of a deletion in the gene coding for S-adenosylmethionine decarboxylase are very sensitive to elevated temperatures when incubated in a polyamine-deficient medium; i.e., growth is inhibited and the cells are killed. This sensitivity is very pronounced at 39 degrees C, but a moderate effect is noted even at 33 to 34 degrees C. These findings support findings from other studies from our laboratory on the importance of polyamines in protecting cell components against damage. The sensitivity of spermidine-deficient cells to the temperature 39 degrees C provides a useful method for screening for polyamine auxotrophs. C1 NIDDKD,BIOCHEM PHARMACOL LAB,BETHESDA,MD 20892. NR 12 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 1996 VL 178 IS 9 BP 2721 EP 2724 PG 4 WC Microbiology SC Microbiology GA UJ122 UT WOS:A1996UJ12200036 PM 8626346 ER PT J AU Birney, M Um, HD Klein, C AF Birney, M Um, HD Klein, C TI Novel mechanisms of Escherichia coli succinyl-coenzyme A synthetase regulation SO JOURNAL OF BACTERIOLOGY LA English DT Article ID DICTYOSTELIUM-DISCOIDEUM; COA SYNTHETASE; PHOSPHORYLATION; PROTEIN; GDP; SUBUNIT; P36 AB Low concentrations of ADP are shown to increase the rate of phosphoenzyme formation of E. coli succinyl-coenzyme A (CoA) synthetase (SCS) without altering the fraction of phosphorylated enzyme. This is true when either ATP or succinyl-Coh and P-i are used to phosphorylate the enzyme. The stimulatory effect of ADP is not altered by sample dilution, is retained upon partial purification of the enzyme, and reflects the binding of ADP to a site other than the catalytic site. GDP also alters the phosphorylation of the E. coli SCS but does so primarily by enhancing the level of the phosphoenzyme and only when ATP is used as the phosphate donor. GDP appears to function by neutralizing the action of a specific inhibitory protein. This inhibitor of SCS allows for interconversion of succinate and succinyl-CoA in a manner dissociated from changes in ATP-ADP metabolism. These previously unidentified and varied mechanisms by which SCS is regulated focus attention on this enzyme as an important control point in determining the cell's potential to meet its metabolic demands. C1 ST LOUIS UNIV,SCH MED,DEPT BIOCHEM & MOLEC BIOL,ST LOUIS,MO 63104. NIDR,IMMUNOL LAB,BETHESDA,MD 20892. FU NHLBI NIH HHS [HL 07050] NR 20 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 1996 VL 178 IS 10 BP 2883 EP 2889 PG 7 WC Microbiology SC Microbiology GA UL275 UT WOS:A1996UL27500020 PM 8631677 ER PT J AU Lobocka, MB Svarchevsky, AN Rybchin, VN Yarmolinsky, MB AF Lobocka, MB Svarchevsky, AN Rybchin, VN Yarmolinsky, MB TI Characterization of the primary immunity region of the Escherichia coli linear plasmid prophage N15 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID SERRATIA-MARCESCENS; CELL-DIVISION; GENE; SEQUENCE; CONSTRUCTION; REPRESSOR; BACTERIA; PROTEIN; INVITRO; OPERON AB N15 is the only bacteriophage of Escherichia coli known to lysogenize as a linear plasmid, Clear-plaque mutations lie in at least two regions of the 46-kb genome, We have cloned, sequenced, and characterized the primary immunity region, immB. This region contains a gene, cB, whose product shows homology to lambdoid phage repressors. The cB3 mutation confers thermoinducibility on N15 lysogens, consistent with CB being the primary repressor of N15, Downstream of cB lies the locus of N15 plasmid replication, Upstream of cB lies an operon predicted to encode two products: one homologous to the late repressor of P22 (Cro), the other homologous to the late antiterminator of phi 82 (Q), The Q-like protein is essential for phage development, We show that CB protein regulates the expression of genes that flank the cB gene by binding to DNA at symmetric 16-hp sites, Three sites are clustered upstream of cB and overlap a predicted promoter of the cro and e-like genes as well as two predicted promoters of cB itself. Two sites downstream of cB overlap a predicted promoter of a plasmid replication gene, repA, consistent with the higher copy number of the mutant, N15cB3. The lender region of repA contains terminators in both orientations and a putative promoter, The organization of these regulatory elements suggests that N15 plasmid replication is controlled not only by CB but also by an antisense RNA and by a balance betweem termination and antitermination. C1 STATE TECH UNIV,DEPT BIOPHYS,ST PETERSBURG 19251,RUSSIA. RP Lobocka, MB (reprint author), NCI,BIOCHEM LAB,NIH,BLDG 37,ROOM 4D-15,BETHESDA,MD 20892, USA. NR 48 TC 26 Z9 27 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 1996 VL 178 IS 10 BP 2902 EP 2910 PG 9 WC Microbiology SC Microbiology GA UL275 UT WOS:A1996UL27500023 PM 8631680 ER PT J AU Stein, U Walther, W Shoemaker, RH AF Stein, U Walther, W Shoemaker, RH TI Vincristine induction of mutant and wild type human multidrug-resistance promoters is cell-type specific and dose-dependent SO JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY LA English DT Article DE multidrug resistance; MDR1 promoter; drug inducibility; CAT assay; colon carcinoma cell lines ID P-GLYCOPROTEIN GENE; COLON-CARCINOMA-CELLS; HUMAN MDR1 GENE; PROTEIN-KINASE; EXPRESSION; ACTIVATION; LINES; MDR-1/P-GLYCOPROTEIN; PURIFICATION; MODULATION AB To investigate multidrug-resistance gene (MDR1) promoter efficacy and drug inducibility in cells with different multidrug-resistance phenotypes, multidrug-resistant HCT15 and drug-sensitive KM12 human colon carcinoma cell lines were transfected with constructs incorporating the chloramphenicol acetyltransferase (CAT) reporter gene, driven by wild-type and point-mutated MDR1 promoter regions. The basal CAT expression level in HCT15 cells was markedly elevated compared to KM12 cells. CAT induction by vincristine was dose-dependent over a broad concentration range (40-500 ng/ml) in both lines. The induction levels were related to the cells' MDR phenotype, with the multidrug-resistant HCT15 cells showing the greater effect. In both cell types, basal and drug-induced CAT expression were significantly enhanced by the point-mutated promoter regions. The findings support the possible exploitation of the MDR1 promoter for construction of drug-inducible and MDR-cell-targeted expression vectors for use in gene therapy. C1 MAX DELBRUCK CTR MOLEC MED,D-13122 BERLIN,GERMANY. RP Stein, U (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702, USA. NR 34 TC 21 Z9 22 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-5216 J9 J CANCER RES CLIN JI J. Cancer Res. Clin. Oncol. PD MAY PY 1996 VL 122 IS 5 BP 275 EP 282 DI 10.1007/BF01261403 PG 8 WC Oncology SC Oncology GA UG537 UT WOS:A1996UG53700003 PM 8609150 ER PT J AU Tournier, S Raynaud, F Gerbaud, P Lohmann, SM Anderson, WB EvainBrion, D AF Tournier, S Raynaud, F Gerbaud, P Lohmann, SM Anderson, WB EvainBrion, D TI Retinoylation of the type II cAMP-binding regulatory subunit of cAMP-dependent protein kinase is increased in psoriatic human fibroblasts SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID RETINOIC ACID RECEPTOR; HUMAN SKIN; GOLGI-COMPLEX; IDENTIFICATION; KERATINOCYTES; EXPRESSION; ACYLATION; INVITRO; CELLS; GENE AB Previously, we have reported a defect in the cAMP-dependent protein kinases (cAMP-PK) in psoriatic cells (i.e., a decrease in 8-azido-[P-32]cAMP binding to the regulatory subunits and a decrease in phosphotransferase activity) which is rapidly reversed with retinoic acid IRA) treatment of these cells. This led us to examine a possible direct interaction between retinoids and the RI and RII regulatory subunits through retinoylation. Retinoylation of RI and RII present in normal and psoriatic human fibroblasts was analysed by [H-3]RA treatment of these cells, followed either by chromatographic separation of the regulatory subunits or by their specific immunoprecipitation. These studies indicated that RI and RII can be retinoylated. [H-3]RA labeling of the RII subunit was significantly (P < 0.005) greater in psoriatic fibroblasts (nine subjects; mean 7.47 relative units +/- 1.37 SEM) compared to normal fibroblasts (eight subjects; mean 2.46 relative units +/- 0.49 SEM). [H-3]RA labeling of and the increase in 8-azido-[P-32]-binding to the RI and RII subunit in psoriatic fibroblasts showed a similar time course, This suggests that the rapid effect of retinoic acid treatment to enhance 8-azido-[P-32]-cAMP binding to the RI and RII in psoriatic fibroblasts may be due, in part, to covalent modification of the regulatory subunits by retinoylation. (C) 1996 Wiley-Liss, Inc. C1 UNIV PARIS 05,FAC SCI PHARMACEUT & BIOL,INSERM U427,F-75006 PARIS,FRANCE. UNIV WURZBURG,MED KLIN,LABOR KLIN BIOCHEM,W-8700 WURZBURG,GERMANY. NCI,CELLULAR ONCOL LAB,DIV CANC BIOL & DIAG,NIH,BETHESDA,MD 20892. NR 36 TC 22 Z9 22 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAY PY 1996 VL 167 IS 2 BP 196 EP 203 DI 10.1002/(SICI)1097-4652(199605)167:2<196::AID-JCP2>3.3.CO;2-M PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA UG060 UT WOS:A1996UG06000002 PM 8613459 ER PT J AU Wu, AJ Chen, ZJ Tsokos, M OConnell, BC Ambudkar, IS Baum, BJ AF Wu, AJ Chen, ZJ Tsokos, M OConnell, BC Ambudkar, IS Baum, BJ TI Interferon-gamma induced cell death in a cultured human salivary gland cell line SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; SJOGRENS-SYNDROME; EPITHELIAL-CELLS; HLA-DR; EXPRESSION; PROLIFERATION; APOPTOSIS; MOLECULES; INVITRO; BINDING AB Increased levels of several cytokines, including interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), have been demonstrated in the salivary gland microenvironment of patients with Sjogren's syndrome (SS). How these cytokines may be contributing to the pathogenesis of the disease is not well understood. This study examined the role of IFN-gamma +/- TNF-alpha on cellular death in a cultured human salivary gland cell line (HSG). Cells treated long-term with IFN-gamma +/- TNF-alpha demonstrate a profound antiproliferative effect with a decrease in cell number to below that initially plated. Treatment of HSG cells with TNF-alpha alone did not have any significant effects on growth but did increase the expression of the IFN-gamma receptor. Cells labelled with propidium iodide and anti-digoxigenin dUTP/dATP were examined by flow cytometry to determine the percentage of cells exhibiting low DNA content and DNA strand breaks. The percentage of cells exhibiting subdiploid DNA and DNA strand breaks increased with increased time of exposure to the cytokines. The maximum percentage of cells exhibiting DNA degradation at 12 days was 58% for cells treated with IFN-gamma + TNF-alpha, 31% for lFN-gamma treated cells, and <5% for TNF-alpha-treated and untreated cells. The cells with subdiploid (<2n) DNA were subsequently demonstrated to represent two populations, both with evidence of increased DNA strand breaks but with differing light scatter characteristics. One population had features of cells undergoing necrosis, whereas the second population exhibited features of apoptosis. These findings were confirmed by transmission electron microscopy. Cells not exposed to cytokines did not exhibit significant evidence of either death process. We conclude that long-term exposure of a human salivary gland epithelial cell line to IFN-gamma +/- TNF-alpha leads to increased DNA degradation and subsequent cell death. This suggests a potential SS disease mechan ism and implicates the role of the epithelial cell in this disease as an important area for future study. (C) 1996 Wiley-Liss, Inc. C1 NIDR,ORAL MED LAB,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. RP Wu, AJ (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,NIH,BLDG 10,RM 1N113,10 CTR DR,MSC 1190,BETHESDA,MD 20892, USA. OI O'Connell, Brian/0000-0003-4529-7664 NR 30 TC 64 Z9 65 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAY PY 1996 VL 167 IS 2 BP 297 EP 304 DI 10.1002/(SICI)1097-4652(199605)167:2<297::AID-JCP14>3.0.CO;2-5 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA UG060 UT WOS:A1996UG06000014 PM 8613471 ER PT J AU Moeller, JR Ishikawa, T Dhawan, V Spetsieris, P Mandel, F Alexander, GE Grady, C Pietrini, P Eidelberg, D AF Moeller, JR Ishikawa, T Dhawan, V Spetsieris, P Mandel, F Alexander, GE Grady, C Pietrini, P Eidelberg, D TI The metabolic topography of normal aging SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE aging, normal; FDG; PET; Scaled Subprofile Model; metabolic topography ID CEREBRAL BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; PARKINSONS-DISEASE; GLUCOSE-UTILIZATION; ALZHEIMERS-DISEASE; MOOD DISORDERS; NORMAL VALUES; HEALTHY-MEN; HUMAN-BRAIN; AGE AB Normal aging is associated with the degeneration of specific neural systems. We used [F-18]fluorodeoxyglucose (FDG)/positron emission tomography (PET) and a statistical model of regional covariation to explore the metabolic topography of this process. We calculated global and regional metabolic rates for glucose (GMR and rCMR(glc)) in two groups of normal subjects studied independently on different tomographs: Group 1-130 normal subjects (62 men and 68 women; range 21-90 years); Group 2-20 normal subjects (10 men and 10 women; range 24-78 years). In each of the two groups, the Scaled Subprofile Model (SSM) was applied to rCMR(glc) data to identify specific age-related profiles. The validity of these profiles as aging markers was assessed by correlating the associated subject scores with chronological age in both normal populations. SSM analysis disclosed two significant topographic profiles associated with aging. The first topographic profile, extracted in an analysis of group 1 normals, was characterized by relative frontal hypometabolism associated with covariate metabolic increases in the parietooccipital association areas, basal ganglia, mid-brain, and cerebellum. Subject scores for this profile correlated significantly with age in both normal groups (R(2) = 0.48 and 0.33, p < 0.0001 for groups 1 and 2, respectively). Because of clinical similarities between normal motoric aging and parkinsonism, we explored the possibility of shared elements in the metabolic topography of both processes. We performed a combined group SSM analysis of the 20 group 2 normals and 22 age-matched Parkinson's disease patients, and identified another aging-related topographic profile. This profile was characterized by relative basal ganglia hypermetabolism associated with covariate decreases in frontal premotor cortex. Subject scores for this profile also correlated significantly with age in both normal groups (group 1: R(2) = 0.30, p < 0.00001; group 2: R(2) = 0.59, p < 0.01). Healthy aging is associated with reproducible topographic covariation profiles associated with specific neural systems. FDG/PET may provide a useful metabolic marker of the normal aging process. C1 N SHORE UNIV HOSP, DEPT NEUROL, MANHASSET, NY 11030 USA. N SHORE UNIV HOSP, DEPT BIOSTAT, MANHASSET, NY 11030 USA. NIA, NEUROSCI LAB, BETHESDA, MD 20892 USA. COLUMBIA UNIV COLL PHYS & SURG, NEW YORK STATE PSYCHIAT INST, DEPT PSYCHIAT, MANHASSET, NY USA. CORNELL UNIV, COLL MED, NEW YORK, NY USA. RI Eidelberg, David/F-5214-2011 NR 57 TC 159 Z9 161 U1 0 U2 1 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 1996 VL 16 IS 3 BP 385 EP 398 PG 14 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA UF710 UT WOS:A1996UF71000005 PM 8621743 ER PT J AU Nakanishi, H Cruz, NF Adachi, K Sokoloff, L Dienel, GA AF Nakanishi, H Cruz, NF Adachi, K Sokoloff, L Dienel, GA TI Influence of glucose supply and demand on determination of brain glucose content with labeled methylglucose SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE cerebral glucose utilization; brain; glucose; methylglucose; barbital; penicillin ID RAT-BRAIN; LUMPED CONSTANT; TRANSPORT; BLOOD; 3-O-METHYL-D-GLUCOSE; PHOSPHORYLATION; 2-DEOXYGLUCOSE; METABOLITES; BARRIER AB The equilibrium brain/plasma distribution ratio for 3-O-methyl-D-glucose (methylglucose) varies with plasma and tissue glucose contents and can be used to determine local glucose levels in brain. This ratio was previously found to rise as brain glucose concentration fell in response to lowered plasma glucose content. The ratios, however, differed with the same tissue glucose levels in conscious and pentobarbital-sedated rats, suggesting that changes in metabolic demand might alter the quantitative relationship between the methylglucose distribution ratio and brain glucose concentration. To examine this possibility, metabolic rate was varied by focal drug application, and hexose concentrations measured in treated and surrounding tissue. When tissue glucose levels were reduced by raised metabolic demand, methylglucose distribution ratios also fell. When brain glucose levels rose due to reduced consumption, the methylglucose distribution ratio also rose. Thus, in contrast to the inverse relationship between brain/plasma methylglucose ratio and brain glucose concentration when brain glucose content is altered secondarily to changes in plasma glucose level, changes in brain glucose content induced by altered glucose utilization cause the brain glucose level and methylglucose distribution ratio to rise and fall in a direct relationship. Determination of brain glucose content from methylglucose distribution ratios must take into account rates of glucose delivery and consumption. C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20895. NR 21 TC 15 Z9 15 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAY PY 1996 VL 16 IS 3 BP 439 EP 449 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA UF710 UT WOS:A1996UF71000010 PM 8621748 ER PT J AU Kim, WB Cho, BY Park, HY Lee, HK Kohn, LD Tahara, K Koh, CS AF Kim, WB Cho, BY Park, HY Lee, HK Kohn, LD Tahara, K Koh, CS TI Epitopes for thyroid-stimulating antibodies in Graves' sera: A possible link of heterogeneity to differences in response to antithyroid drug treatment SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID IDIOPATHIC MYXEDEMA PATIENTS; HUMAN THYROTROPIN RECEPTOR; 3RD CYTOPLASMIC LOOP; TSH-RECEPTOR; BLOCKING ANTIBODIES; GONADOTROPIN RECEPTORS; SYNTHETIC PEPTIDES; IMMUNOGLOBULIN-G; CELLS; DISEASE AB To evaluate the extent and clinical relevance of epitope heterogeneity for stimulating TSH receptor antibodies (TSHRAbs), we measured the activity of IgG preparations from 66 untreated patients with Graves' disease using Chinese hamster ovary (CHO) cells transfected with wild-type human TSHR and two TSHR chimeras with residues 9-165 (Mc1+2) or 90-165 (Mc2) substituted by equivalent residues of the LH/CG receptor. IgG from 68% of patients lose all of the stimulating TSHRAb activity with the chimeras; IgG from 27% lose most of the activity. Thus, we show that 95% of patients have stimulating TSHRAbs that require epitopes on the N-terminal portion of the extracellular domain of the TSHR and demonstrate the importance of epitopes within residues 90-165 for the first time. Heterogeneous epitope distribution, residual activity with one or both chimeras, i.e. with epitopes other than on the N-terminus of the TSHR, occurred in 21 patients (group A). Forty-five patients with homogeneous epitope distribution (group B) had stimulating TSHRAbs that depended only on epitopes on the N-terminus of the TSHR, Patients in group A were more likely to become euthyroid during antithyroid drug therapy and to do so more quickly than group B patients. The CHO-human TSHR cell system described herein appears to be as effective as the FRTL-5 rat thyroid system in stimulating TSHRAb detection; however, the two systems appear to measure different antibody populations in about 30% of cases. Further, stimulating TSHRAb activities measured in the FRTL-5 system tend to correlate better with goiter size and Tc-99m pertechnetate uptake, whereas stimulating activities measured in the CHO-human TSHR/chimera system correlate better with free T-4 and T-3 levels. C1 SEOUL NATL UNIV, COLL MED, DEPT INTERNAL MED, SEOUL 151, SOUTH KOREA. NIDDKD, METAB DIS BRANCH, CELL REGULAT SECT, NIH, BETHESDA, MD 20892 USA. CHIBA UNIV, SCH MED, DEPT INTERNAL MED 2, CHIBA 260, JAPAN. OI Kim, Won Bae/0000-0003-4544-1750 NR 37 TC 61 Z9 62 U1 0 U2 1 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 1996 VL 81 IS 5 BP 1758 EP 1767 DI 10.1210/jc.81.5.1758 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UK198 UT WOS:A1996UK19800018 PM 8626830 ER PT J AU GarciaCaballero, T Morel, G Gallego, R Fraga, M Pintos, E Gago, D Vonderhaar, BK Beiras, A AF GarciaCaballero, T Morel, G Gallego, R Fraga, M Pintos, E Gago, D Vonderhaar, BK Beiras, A TI Cellular distribution of prolactin receptors in human digestive tissues SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GROWTH-HORMONE; MONOCLONAL-ANTIBODIES; PLACENTAL LACTOGEN; BINDING DOMAIN; LYMPHOMA-CELLS; RAT-LIVER; EXPRESSION; FAMILY; GENE; LOCALIZATION AB In the present study we analyzed the expression of prolactin receptors (PRLR) in human digestive tissues by immunohistochemistry. PRLR immunoreactivity was primarily localized in the cytoplasm. However, in some organs (liver and salivary glands) a nuclear positivity was also found. The liver was used as control and showed a diffuse immunostaining in the parenchymal cells. In the gastrointestinal tract, PRLR immunoreactivity was observed in the mucosa, muscularis layer, and nervous plexuses. The more intense immunostaining in the mucosa of the different segments was as follows: esophagus, superficial layers of the stratified squamous epithelium and mucous glands; stomach, parietal cells; small intestine, absorptive and Paneth cells; and colon, surface epithelium and superficial half of the crypts of Lieberkuhn. In the salivary glands, immunoreactivity was strong in the mucous tubules, moderate in the ducts, and weak in the serous cells. Endocrine pancreas showed a more intense immunoreactivity than the pancreatic acini. By serial sections of the islets of Langerhans we showed that immunostaining was confined to B cells. These findings demonstrate the widespread distribution of PRLR in human digestive tissues and its localization both in cytoplasms and nuclei. C1 INST PASTEUR, CNRS UNITE RECH ASSOCIEE 1459, LYON, FRANCE. SCH MED & GEN HOSP GALICIA, DEPT & SERV PATHOL, SANTIAGO, SPAIN. NCI, TUMOR IMMUNOL & BIOL LAB, BETHESDA, MD USA. RP GarciaCaballero, T (reprint author), UNIV SANTIAGO DE COMPOSTELA, SCH MED, DEPT MORPHOL SCI, SAN FRANCISCO S-N, E-15705 SANTIAGO, SPAIN. RI Garcia-Caballero, Tomas/H-7213-2015 NR 59 TC 24 Z9 25 U1 0 U2 1 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 1996 VL 81 IS 5 BP 1861 EP 1866 DI 10.1210/jc.81.5.1861 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UK198 UT WOS:A1996UK19800036 PM 8626848 ER PT J AU Leong, GM MercadoAsis, LB Reynolds, JC Hill, SC Oldfield, EH Chrousos, GP AF Leong, GM MercadoAsis, LB Reynolds, JC Hill, SC Oldfield, EH Chrousos, GP TI The effect of Cushing's disease on bone mineral density, body composition, growth, and puberty: A report of an identical adolescent twin pair SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOSTEROID-INDUCED OSTEOPOROSIS; HORMONE-BINDING PROTEIN; CIRCADIAN-RHYTHM; CHILDREN; QUANTITATION; OSTEOCALCIN; ASSAY; SERUM; MASS AB As endogenous Cushing's syndrome (CS) in children occurs during a critical developmental period, when the majority of peak bone mass is acquired, we hypothesized that children with CS might be at an increased risk of osteoporosis. To determine the effects of CS on bone density, bone metabolism, and growth, we studied a 15-yr-old female identical twin pair, one of whom had CS (twin A), and the other of whom was healthy (twin B). Before therapy for GS, twin A showed a severe loss of bone mineral density [BMD; -3.2 so at the lumbar spine (LS)] compared to twin B (-0.1 SE), which in twin A was associated with low serum osteocalcin levels and urinary pyridinium cross-link excretion. Cure of CS in twin A led to a marked increase in these bone markers, suggesting a state of active bone remodeling. After 27 months of follow-up, even though twin A's BMD improved significantly, it still remained abnormal [-1.9 so at LS compared with that of twin B (0 SD)], suggesting that twin A continued to be at increased long term risk of osteoporosis. In addition, as a consequence of CS, twin A's final height was 21 cm less than that of her identical twin. We recommend that all children with CS should have BMD monitored after treatment to determine the longterm risk of osteoporosis. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. WARREN G MAGNUSON CLIN CTR, HENRY M JACKSON FDN, DEPT NUCL MED, BETHESDA, MD 20892 USA. WARREN G MAGNUSON CLIN CTR, HENRY M JACKSON FDN, DEPT DIAGNOST RADIOL, BETHESDA, MD 20892 USA. NINCDS, NIH, SURG NEUROL BRANCH, BETHESDA, MD 20892 USA. NR 53 TC 40 Z9 40 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 1996 VL 81 IS 5 BP 1905 EP 1911 DI 10.1210/jc.81.5.1905 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UK198 UT WOS:A1996UK19800044 PM 8626856 ER PT J AU Magiakou, MA Mastorakos, G Rabin, D Dubbert, B Gold, PW Chrousos, GP AF Magiakou, MA Mastorakos, G Rabin, D Dubbert, B Gold, PW Chrousos, GP TI Hypothalamic corticotropin-releasing hormone suppression during the postpartum period: Implications for the increase in psychiatric manifestations at this time SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PITUITARY-ADRENAL AXIS; PLASMA-CORTISOL; CUSHINGS-SYNDROME; LATE PREGNANCY; PUERPERIUM; DEPRESSION; RESPONSES; RECOVERY; STRESS; MOOD AB The third trimester of human pregnancy is characterized by a hyperactive hypothalamic-pituitary-adrenal ards, possibly driven by progressively increasing circulating levels of placental CRH and gradually decreasing levels of CRH-binding protein. The postpartum period, on the other hand, is characterized by an increased vulnerability to psychiatric manifestations (postpartum ''blues,'' depression, and psychosis), a phenomenon compatible with suppressed hypothalamic CRH secretion. To investigate the hypothesis that the postpartum period is associated with suppression of hypothalamic CRH secretion, we studied prospectively 17 healthy euthymic women (mean +/- SE age, 32.0 +/- 1.1 yr) with no prior history of depression, starting at the 20th week of gestation. Psychometric testing was performed monthly during pregnancy and postpartum on day 2 and weeks 2, 3, 6, 8, 12, 16, and 20, whereas serial ovine (o) CRH tests were performed postpartum at 3, 6, and 12 weeks. While pregnant, all 17 subjects remained euthymic; in the postpartum period, 7 women developed the ''blues,'' and 1 developed depression. Overall, the mean plasma ACTH response to an iv bolus of 1 mu g/kg oCRH was markedly blunted at 3 and 6 weeks, but normal at 12 weeks postpartum, whereas the mean plasma cortisol response was at the upper limit of normal at all 3 times. These data are compatible with a suppressed hypothalamic CRH neuron that gradually returns to normal while hypertropic adrenal cortexes are progressively down-sizing. When the postpartum ACTH responses to oCRH were analyzed separately for the euthymic women and the women who had the ''blues'' or depression, the blunting of ACTH was significantly more severe and long lasting in the latter group; this was observed at all 3 times of testing. We conclude that there is central suppression of hypothalamic CRH secretion in the postpartum, which might explain the increased vulnerability to the affective disorders observed during this period. The suppressed ACTH response to oCRH might serve as a biochemical marker of the postpartum ''blues'' or depression. C1 NICHHD, NATL INST HLTH, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NIMH, NATL INST HLTH, CLIN NEUROENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NR 51 TC 140 Z9 142 U1 1 U2 6 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 1996 VL 81 IS 5 BP 1912 EP 1917 DI 10.1210/jc.81.5.1912 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UK198 UT WOS:A1996UK19800045 PM 8626857 ER PT J AU Nunez, SB Municchi, G Barnes, KM Rose, SR AF Nunez, SB Municchi, G Barnes, KM Rose, SR TI Insulin-like growth factor I (IGP-I) and IGF-binding protein-3 concentrations compared to stimulated and night growth hormone in the evaluation of short children - A clinical research center study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DEFICIENCY; DIAGNOSIS; IGFBP-3; SECRETION; PUBERTY; SERUM; GIRLS AB To evaluate the relative usefulness of insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) in screening for GH status, GH stimulation (arginine-insulin/L-DOPA) tests and overnight GH studies (every 20 min sampling) were performed in 104 healthy short children (32 girls), aged 3-16 yr (height, -1.8 or more SD). IGFBP-3 had no advantage over IGF-I in screening sensitivity or specificity. IGF-I correlated with mean nighttime GH. Both IGF-I and IGFBP-3 correlated with peak stimulated GH. To identify more than 90% of children with GH deficiency (GHD) and borderline GHD, the mean values for age for IGF-I and IGFBP-3 were required as the cut-off criterion. However, at this criterion, 70% or more of idiopathic short stature (ISS) children would have to undergo testing to identify 90% of GHD or borderline GHD. More stringent criteria (-1.0, -1.64, and -2.0 SD) were more specific, but lost sensitivity. A practical application is suggested. Screening use of IGF-I with criterion of -1.0 SD would identify a subgroup that includes 88% of GHD, 71% of borderline GHD, and 46% of ISS. Both IGF-I and IGFBP-3 higher than -1.0 SD would accurately identify 68% of ISS as not needing GH testing. Evaluation of growth velocity would identify the remaining children requiring definitive testing. Thus, combined screening for GHD using both IGF-I and IGFBP-3 has no better sensitivity than either test alone. However, such combined screening will improve the specificity and thus decrease the number of normal but short children who might otherwise undergo unnecessary testing. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. UNIV TENNESSEE, DEPT PEDIAT, MEMPHIS, TN 38103 USA. FU NCRR NIH HHS [5M01-RR-00997] NR 26 TC 52 Z9 52 U1 0 U2 1 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 1996 VL 81 IS 5 BP 1927 EP 1932 DI 10.1210/jc.81.5.1927 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UK198 UT WOS:A1996UK19800047 PM 8626859 ER PT J AU Adesanya, OO Zhou, J Bondy, CA AF Adesanya, OO Zhou, J Bondy, CA TI Sex steroid regulation of insulin-like growth factor system gene expression and proliferation in primate myometrium SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; ENDOMETRIAL STROMAL CELLS; MONOCLONAL-ANTIBODY KI-67; FACTOR BINDING PROTEIN-1; TYROSINE KINASE-ACTIVITY; I IGF-I; NUCLEAR ANTIGEN; RAT UTERUS; UTERINE LEIOMYOMATA; RECEPTOR AB To investigate the role of locally produced insulin-like growth factors (IGFs) in sex steroid-induced growth in the primate uterus, ovariectomized rhesus monkeys were treated with placebo (control), estradiol (E(2)) alone, or E(2) plus progesterone (P-4). After 2 weeks, uteri were removed, and serial thin uterine sections were analyzed by in situ hybridization for IGF-I, IGF-II, and IGF-I and -II receptor messenger ribonucleic acids (mRNAs) and by immunocytochemistry for the cell proliferation-specific antigen Ki-67. IGF-I and IGF-II and both IGF receptor mRNAs are coexpressed by smooth muscle cells, supporting the possibility of autocrine/paracrine IGF action in stimulating myometrial growth. IGF-I mRNA is barely detected in control myometrium, is significantly increased by E(2) treatment, and is augmented even more by the combination of E(2) and P-4 treatment, whereas little change is noted in myometrial IGF-II or IGF-I receptor mRNA levels. Ki-67-positive myometrial nuclei are also significantly increased by E(2) and are augmented even more by E(4) plus P-4 treatment, with a correlation between local IGF-I mRNA concentration and local Ki-67-positive cell count of r = 0.891 (P = 0.003). These data provide direct experimental evidence for regulation of IGF-I gene expression by sex steroids in the primate uterus in vivo and implicate local IGF-I action in both estrogen- and P-4-induced myometrial growth. RP Adesanya, OO (reprint author), NICHHD, DEV ENDOCRINOL BRANCH,NIH,10 CTR DR,MSC 1862, BLDG 10, ROOM 10N 262, BETHESDA, MD 20892 USA. NR 40 TC 45 Z9 45 U1 0 U2 1 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 1996 VL 81 IS 5 BP 1967 EP 1974 DI 10.1210/jc.81.5.1967 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UK198 UT WOS:A1996UK19800054 PM 8626866 ER PT J AU Corti, MC Salive, ME Guralnik, JM AF Corti, MC Salive, ME Guralnik, JM TI Serum albumin and physical function as predictors of coronary heart disease mortality and incidence in older persons SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE serum albumin; disability; elderly; coronary heart disease; risk factors; mortality ID LOW-DENSITY LIPOPROTEIN; RISK-FACTORS; CARDIOVASCULAR-DISEASE; ASSOCIATION; CHOLESTEROL; EXERCISE; BENEFITS; ADULTS; DEATH; LIFE AB The role of traditional risk factors in predicting coronary heart disease (CHD) among men and women aged 65 years and over has been extensively debated, but the search for risk factors that are distinctive in the elderly is still ongoing. The relation of serum albumin levels and physical disability to risk of CHD morality and incidence was prospectively assessed in a cohort of 4116 men and women, aged 71 years and over, who were evaluated in 1987-1989 and followed for a mean of 4.0 years. Outcome events were based on death certificates and Medicare hospitalization records. Analyses were adjusted for major CHD risk factors. There were 275 CHD deaths (16.8/1000 person-years) among all participants and 503 incident (fatal and nonfatal) CHD events (39.4 per 1000 person-years) among participants free of prevalent CHD during the observation period. The relative risk (RR) of CHD morality for women with an albumin concentration <38 g/liter was 2.5 times higher than for women with albumin >43 g/liter (RR 2.5; 95% confidence interval [CI], 1.4-4.6). There was a significant and graded increase in CHD incidence with decreasing albumin concentration in women but not in men. The presence of physical disability doubled the risk of CHD mortality among both men and women, an increase in risk that was comparable to that imposed by a previous myocardial infarction and was independent of other coronary risk factors. Disability had a lesser impact on CHD incidence, which was significant only in women. Low albumin concentration (<38 g/liter) identifies a group of women at higher risk of CHD mortality and incidence. Physical disability is an independent predictor of CHD mortality in both men and women and for CHD incidence only in women. RP Corti, MC (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,NIH,7201 WISCONSIN AVE,ROOM 3C-309,BETHESDA,MD 20892, USA. FU NIA NIH HHS [N01-AG-0-2106, N01-AG-0-2104, N01-AG-0-2107] NR 51 TC 61 Z9 63 U1 3 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD MAY PY 1996 VL 49 IS 5 BP 519 EP 526 DI 10.1016/0895-4356(95)00562-5 PG 8 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA UN515 UT WOS:A1996UN51500004 PM 8636725 ER PT J AU Silverman, DT Schiffman, M Devesa, S AF Silverman, DT Schiffman, M Devesa, S TI Diagnostic certainty in pancreatic cancer SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Letter RP Silverman, DT (reprint author), NCI,BETHESDA,MD 20892, USA. NR 4 TC 18 Z9 19 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD MAY PY 1996 VL 49 IS 5 BP 601 EP 602 DI 10.1016/0895-4356(95)00508-0 PG 2 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA UN515 UT WOS:A1996UN51500015 PM 8636736 ER PT J AU Koff, WC Schultz, AM AF Koff, WC Schultz, AM TI Progress and challenges toward an AIDS vaccine: Brother, can you spare a paradigm? SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Review DE AIDS vaccine; human immunodeficiency virus (HIV) variation; correlates of immunity ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE-DEFICIENCY SYNDROME; INFECTION; IMMUNIZATION; PROTECTION; RISK AB The development of a safe and effective vaccine for prevention of AIDS has thus far proven to be exceedingly difficult due to the complexities associated with HIV pathogenesis including but not limited to antigenic hypervariability, multiple routes and modes of transmission, a lack of defined correlates of protective immunity, and a tropism for infection of immunoregulatory cells which are essential for orchestrating an effective host immune response. Recent observations, including the identification of significant differences between primary isolates of HIV circulating in the population and laboratory-adapted isolates, animal model protection studies demonstrating prevention of AIDS-like disease progression in nonhuman primates in the absence of sterilizing immunity, and epidemiologic studies which question the current dogma surrounding HIV variation and control, have led to the development of novel approaches for antigen presentation and adjuvant development targeted at AIDS vaccine development. The goal of developing a safe and effective AIDS vaccine will likely occur when continued advances in understanding the immunopathogenesis Of HIV is balanced with a healthy dose of empirical testing of innovative candidate AIDS vaccines. C1 NIAID,DIV AIDS,NIH,BETHESDA,MD 20892. RP Koff, WC (reprint author), UNITED BIOMED INC,VACCINE RES & DEV,25 DAVIDS DR,HAUPPAUGE,NY 11788, USA. NR 63 TC 3 Z9 3 U1 0 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD MAY PY 1996 VL 16 IS 3 BP 127 EP 133 DI 10.1007/BF01540910 PG 7 WC Immunology SC Immunology GA UL256 UT WOS:A1996UL25600001 PM 8734355 ER PT J AU Kalogeras, KT Nieman, LK Friedman, TC Doppman, JL Cutler, GB Chrousos, GP Wilder, RL Gold, PW Yanovski, JA AF Kalogeras, KT Nieman, LK Friedman, TC Doppman, JL Cutler, GB Chrousos, GP Wilder, RL Gold, PW Yanovski, JA TI Inferior petrosal sinus sampling in healthy human subjects reveals a unilateral corticotropin-releasing hormone-induced arginine vasopressin release associated with ipsilateral adrenocorticotropin secretion SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE hypothalamus; median eminence; adenohypophysis; neurohypophysis; oxytocin ID DEPENDENT CUSHINGS-DISEASE; PITUITARY-GLAND; AUTORADIOGRAPHIC LOCALIZATION; OXYTOCIN INFUSION; FACTOR RECEPTORS; INTERMEDIATE LOBE; MEDIAN-EMINENCE; FACTOR CRF; RAT; CORTISOL AB Arginine vasopressin (AVP) acts synergistically with corticotropin-releasing hormone (CRH) to stimulate ACTH release from the anterior pituitary, In a previous study of bilateral simultaneous inferior petrosal sinus (IFS) sampling in healthy human subjects, we observed lateralized ACTH secretion, suggesting lateralized secretion of an ACTH-regulating hypothalamic factor, To investigate this possibility, we measured ACTH, CRH, AVP, and oxytocin (OT) levels in the IFS and the peripheral circulation in nine normal volunteers, before and after 1 mu g/kg i.v. bolus ovine CRH (oCRH). At baseline, ACTH, AVP, and OT exhibited a significant (P < 0.05) two to threefold intersinus gradient (ISG), indicating the existence of a dominant petrosal sinus, Endogenous CRH was undetectable in all samples, Despite similar exogenous oCRH levels in both petrosal sinuses, oCRH caused a significant increase (P < 0.001) in the ACTH ISG (15.8+/-5.6, mean+/-SEM), suggesting increased responsiveness of one dominant side of the anterior pituitary. This was associated with an ipsilateral CRH-induced AVP release and a significant increase (P < 0.01) in the AVP ISG (8.6+/-2.3), suggesting lateralized AVP secretion by the hypothalamus. Furthermore, the increased AVP ISG after oCRH correlated strongly with the ACTH ISG (r = 0.92, P < 0.01), oCRH administration did not affect OT, These findings suggest that there is a dominant petrosal sinus in healthy volunteers that appears to reflect a dominant side of the adenohypophysis, characterized by increased functional activity and/or responsiveness of the pituitary corticotrophs. This may reflect lateralized hypothalamic and/or suprahypothalamic function resulting in CRH-responsive lateralized secretion of AVP from parvocellular andlor magnocellular axons in the median eminence and the posterior pituitary. Although the functional and teleologic significance of these findings remains to be investigated, our data suggest a novel mechanism for CRH-mediated ACTH release, namely CRH-induced release of AVP which then enhances CRH action on the corticotrophs. Furthermore, our data represent the first direct evidence for the concept of brain lateralization with respect to neuroendocrine secretion. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NIAMSD,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NIAMSD,WARREN GRANT MAGNUSON CLIN CTR,OFF DIRECTOR,BETHESDA,MD 20892. NIAMSD,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,CEDARS SINAI MED CTR,SCH MED,DEPT MED,LOS ANGELES,CA 90048. RP Kalogeras, KT (reprint author), UNIV MISSISSIPPI,MED CTR,SCH MED,LAB CLIN NEUROENDOCRINOL,DEPT PSYCHIAT & HUMAN BEHAV,JACKSON,MS 39216, USA. NR 54 TC 32 Z9 32 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY 1 PY 1996 VL 97 IS 9 BP 2045 EP 2050 DI 10.1172/JCI118640 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UJ399 UT WOS:A1996UJ39900008 PM 8621793 ER PT J AU Collier, MC Stock, F DeGirolami, PC Samore, MH Cartwright, CP AF Collier, MC Stock, F DeGirolami, PC Samore, MH Cartwright, CP TI Comparison of PCR-based approaches to molecular epidemiologic analysis of Clostridium difficile SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; FIELD GEL-ELECTROPHORESIS; POLYMERASE CHAIN-REACTION; OUTBREAK; DIARRHEA AB Representative isolates of the 10 serogroups of Clostridium difficile and 39 clinical isolates (30 toxigenic and 9 nontoxigenic), including 5 isolates from a confirmed nosocomial outbreak, were analyzed by using two previously described arbitrary-primer PCR (AP-PCR) molecular typing methodologies (AP-PG05 and AP-ARB11) and PCR ribotyping. The two AP-PCR methods investigated gave comparable results; AP-PG05 and AP-ARB11 identified 8 and 7 groups among the serogroup isolates and classified the clinical isolates into 21 and 20 distinct groups, respectively. PCR ribotyping also identified 8 unique groups among the serogroup isolates but classified the clinical isolates into 23 groups. In addition, when results obtained by the PCR methods were compared with typing data generated by pulsed-field gel electrophoresis (PFGE), PCR ribotyping and PFGE were found to be in agreement for 83% (29 of 35) of isolates typeable by both techniques, while AP-PG05 was in agreement with PFGE for 60% (20 of 33) and AP-ARB11 was in agreement with PFGE for only 44% (17 of 36). These results indicate that PCR ribotyping is a more discriminatory approach than AP-PCR for typing C. difficile and, furthermore, that this technique generates results that are in higher concordance with those obtained by using an established method for differentiating isolates of this organism on a molecular level than are results generated by using AP-PCR. C1 NIH,MICROBIOL SERV,DEPT CLIN PATHOL,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892. NEW ENGLAND DEACONESS HOSP,DIV INFECT DIS,BOSTON,MA 02215. NEW ENGLAND DEACONESS HOSP,DEPT PATHOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. NR 19 TC 31 Z9 31 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 1996 VL 34 IS 5 BP 1153 EP 1157 PG 5 WC Microbiology SC Microbiology GA UF570 UT WOS:A1996UF57000021 PM 8727893 ER PT J AU Perloff, M Norton, L Korzun, AH Wood, WC Carey, RW Gottlieb, A Aust, JC Bank, A Silver, RT Saleh, F Canellos, GP Perry, MC Weiss, RB Holland, JF AF Perloff, M Norton, L Korzun, AH Wood, WC Carey, RW Gottlieb, A Aust, JC Bank, A Silver, RT Saleh, F Canellos, GP Perry, MC Weiss, RB Holland, JF TI Postsurgical adjuvant chemotherapy of stage II breast carcinoma with or without crossover to a non-cross-resistant regimen: A cancer and leukemia group B study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RANDOMIZED TRIAL; THERAPY; METHOTREXATE; SENSITIVITY; ADRIAMYCIN; MODELS AB Purpose: To compare two cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone (CMFVP) regimens with a doxorubicin-based regimen-vinblastine, doxorubicin, thiotepa, and Halotestin (Upjohn, Kalamazoo, MI) (VATH)-in patients with stage II node-positive breast carcinoma. Methods: Nine hundred forty-five women were treated with a 6-week induction course of CMFVP. They were then randomized to receive one of two consolidation CMFVP regimens: 6-week courses or 2-week courses. Following completion of CMFVP consolidation, patients were again randomized to either continue the CMFVP regimen or to receive six escalating doses of VATH. Results: Among all patients, with a median follow-up time of 11.5 years, there is no statistically significant difference in disease-free survival (DFS) between the two consolidation CMFVP regimens, VATH intensification treatment is statistically significantly superior to CMFVP in terms of DFS (P = .0040), For patients with one to three involved nodes, there is currently no significant difference between VATH and CMFVP; however, among those with four or more positive lymph nodes, there is a significant difference in favor of VATH (P = .0037). There is also improved overall survival with VATH (P = .043; median, > 14 years v 10 years), This difference is also statistically significant in patients with four or more involved lymph nodes, among postmenopausal patients, and among postmenopausal estrogen receptor-positive patients. Conclusion: Chemotherapy with crossover to escalating dose of VATH following CMFVP was well tolerated and effective, Inauguration of VATH as a treatment intensification at the eighth month produced a major increase in relapse-free and overall survival, The observation that sensitivity to VATH is retained 50 long after mastectomy raises questions about the proper duration of adjuvant chemotherapy and lends support to further investigation of crossover designs in future trials of postoperative adjuvant chemotherapy regimens. (C) 1996 by American Society of Clinical Oncology. C1 NCI,BETHESDA,MD 20892. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. COLUMBIA PRESBYTERIAN MED CTR,NEW YORK,NY. NEW YORK HOSP,CORNELL MED CTR,NEW YORK,NY 10021. MT SINAI HOSP,NEW YORK,NY 10029. SUNY SYRACUSE,HLTH SCI CTR,SYRACUSE,NY 13210. EMORY UNIV,SCH MED,ATLANTA,GA 30322. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. DANA FARBER CANC INST,BOSTON,MA 02115. ONCOL ASSOCIATES SAN DIEGO,SAN DIEGO,CA. UNIV MISSOURI,ELLIS FISCHEL CANC CTR,COLUMBIA,MO. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. FU NCI NIH HHS [CA12449, CA07968, CA33601] NR 30 TC 49 Z9 49 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1996 VL 14 IS 5 BP 1589 EP 1598 PG 10 WC Oncology SC Oncology GA UJ403 UT WOS:A1996UJ40300025 PM 8622076 ER PT J AU Offit, K Biesecker, BB Burt, RW Clayton, EW Garber, JE Kahn, MJE AF Offit, K Biesecker, BB Burt, RW Clayton, EW Garber, JE Kahn, MJE TI Statement of the American Society of Clinical Oncology: Genetic testing for cancer susceptibility SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article AB As the leading organization of physicians who treat people with cancer, the American Society of Clinical Oncology (ASCO) recognizes that cancer specialists must be fully informed of the range of issues involved in genetic testing for cancer risk. The newly discovered and still developing ability to identify individuals at highest risk for cancer holds the promise of improved prevention and early detection of cancers. It also poses potential medical, psychological, and other personal risks that must be addressed in the context of informed consent for genetic testing. ASCO firmly believes that any physician who offers genetic testing should be aware of, and able to communicate, the benefits and limits of current testing procedures, and the range of prevention and treatment options available to patients and their families. For these reasons, ASCO endorses the following principles: ASCO affirms the role of clinical oncologists in documenting a family history of cancer in their patients, providing counseling regarding familial cancer risk and options for prevention and early detection, and recognizing those families for which genetic testing may serve as an aid in counseling. To the greatest extent possible, genetic testing for cancer susceptibility should be performed in the setting of longterm outcome studies. ASCO endorses the formulation and implementation of a notional cooperative study/registry with appropriate confidentiality to define the clinical significance of mutations in known cancer susceptibility genes. ASCO is committed to providing educational opportunities for physicians concerning methods of quantitative cancer risk assessment, genetic testing, and pre- and post-test genetic counseling so that oncologists may more responsibly integrate genetic counseling and testing into the practice of clinical and preventive oncology. Oncologists must assure that informed consent has been given by the patient as an integral part of the process of genetic predisposition testing, whether such testing is offered on a clinical or research basis. ASCO recommends that cancer predisposition testing be offered only when: 1) the person has a strong family history of cancer or very early age of onset of disease; 2) the test can be adequately interpreted; and 3) the results will influence the medical management of the patient or family member. As clinical testing becomes more widely available, the Society encourages oncologists to utilize laboratories committed to the validation of testing methodologies, and to facilitate families' participation in long-term outcome studies. ASCO recommends that oncologists include in pre- and post-test counseling discussion of possible risks and benefits of cancer early detection and prevention modalities, which have presumed but unproven efficacy for individuals at the highest hereditary risk for cancer. ASCO endorses efforts to strengthen regulatory authority over laboratories that provide cancer predisposition tests that will be utilized to inform clinical decisions. These regulatory requirements should include appropriate oversight of the products used in genetic testing, interlaboratory comparisons of reference samples, as well as quality control mechanisms. ASCO endorses all efforts including legislation to prohibit discrimination by insurance companies or employers based on an individual's inherited susceptibility to cancer. All individuals at hereditary risk for cancer should have access to appropriate genetic testing and associated medical care, which should be covered by public and private third-party payers. ASCO endorses continued support of patient-oriented research to analyze the psychological impact of genetic testing of at-risk populations. C1 MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. UNIV UTAH,SALT LAKE CITY,UT 84112. VANDERBILT UNIV,NASHVILLE,TN 37240. DANA FARBER CANC INST,BOSTON,MA 02115. NATL BREAST CANC COALIT,RICHMOND,VA. UNIV MICHIGAN,ANN ARBOR,MI 48109. UNIV TEXAS,MD ANDERSON CANCER CTR,HOUSTON,TX 77030. WASHINGTON UNIV,SCH MED,ST LOUIS,MO 63130. UNIV PENN,PHILADELPHIA,PA 19104. RP Offit, K (reprint author), AMER SOC CLIN ONCOL,225 REINEKERS LANE,SUITE 650,ALEXANDRIA,VA 22314, USA. NR 15 TC 450 Z9 453 U1 0 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1996 VL 14 IS 5 BP 1730 EP 1736 PG 7 WC Oncology SC Oncology GA UJ403 UT WOS:A1996UJ40300043 ER PT J AU Lin, A Longy, M Goldstein, A Mulvihill, J Ponder, B Tucker, M AF Lin, A Longy, M Goldstein, A Mulvihill, J Ponder, B Tucker, M TI Localization of Cowden's disease gene to chromosome 10022-23. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 UNIV PITTSBURGH,PITTSBURGH,PA 15260. INT BERGONIE,BORDEAUX,FRANCE. NCI,BETHESDA,MD 20892. UNIV CAMBRIDGE,CAMBRIDGE,ENGLAND. DANA FARBER CANC INST,BOSTON,MA 02115. RI Tucker, Margaret/B-4297-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1996 VL 14 IS 5 BP 2003 EP 2003 PG 1 WC Oncology SC Oncology GA UJ403 UT WOS:A1996UJ40300054 ER PT J AU Miller, LL Korn, EL Stevens, DS Janik, JE Gause, BL Kopp, WC Longo, DL AF Miller, LL Korn, EL Stevens, DS Janik, JE Gause, BL Kopp, WC Longo, DL TI Abrogation of the hematological activities of the GM-CSF/IL-3 fusion protein (PIXY321) by anti-PIXY321 antibodies in cancer patients receiving high-dose carboplatin: Results of a phase I study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI,BRMP,FREDERICK,MD 21701. NCI,CTEP,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1996 VL 14 IS 5 BP 2012 EP 2012 PG 1 WC Oncology SC Oncology GA UJ403 UT WOS:A1996UJ40300063 ER PT J AU Goldberg, ME AF Goldberg, ME TI Mindblindness - BaronCohen,S SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Book Review ID CORTEX; NEURONS; MONKEY RP Goldberg, ME (reprint author), NEI,SENSORIMOTOR RES LAB,BLDG 49,ROOM 2A-50,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD ST JOURNALS DEPT, CAMBRIDGE, MA 02142 SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD MAY PY 1996 VL 8 IS 3 BP 308 EP 309 DI 10.1162/jocn.1996.8.3.308 PG 2 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA UV315 UT WOS:A1996UV31500007 PM 23968155 ER PT J AU Bartlett, ML Buvat, I Vaquero, JJ Mok, D Dilsizian, V Bacharach, SL AF Bartlett, ML Buvat, I Vaquero, JJ Mok, D Dilsizian, V Bacharach, SL TI Measurement of myocardial wall thickening from PET/SPECT images: Comparison of two methods SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE heart; emission computed tomography; image registration ID POSITRON EMISSION TOMOGRAPHY; COMPUTED-TOMOGRAPHY; VALIDATION; PERFUSION AB Purpose: We compared two methods for measuring myocardial wall thickening from nuclear medicine perfusion scans. The first method uses the percent change in peak activity, and the second method models a profile measured across the myocardium. Method: Mathematical simulations of the myocardium were used, In addition, images with PET or SPECT resolution were created from real MR images. Known amounts of noise were then added. Results: The percent peak thickening (%PT) is nonlinear with true percent thickening, especially for PET resolutions [7 mm full width at half-maximum (FWHM)]. For the peak method, low levels of noise (10%) introduced an error of 8%PT for PET and of 16%PT for SPECT. Additional smoothing reduced these errors, For the fitted model, at 10% noise, the error in thickening was large: 2.3 mm for PET and 7.8 mm for SPECT. Conclusion: The fitted model works well only with good resolution and low noise (e.g., 7 mm FWHM and 10%). The peak method is also sensitive to noise, especially for poorer resolutions. Additional smoothing gives more reliable results for the peak method but not the fitted method. The peak method is therefore the more generally reliable, but even this method may only allow classification of myocardial thickening into broad categories. C1 NIH, DEPT NUCL MED, BETHESDA, MD 20892 USA. CNRS, INSERM, U66, PARIS, FRANCE. UNIV POLITECN MADRID, GRP BIOINGN & TELEMED, MADRID, SPAIN. RI Vaquero, Juan Jose/D-3033-2009 OI Vaquero, Juan Jose/0000-0001-9200-361X NR 13 TC 13 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAY-JUN PY 1996 VL 20 IS 3 BP 473 EP 481 DI 10.1097/00004728-199605000-00031 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UK882 UT WOS:A1996UK88200031 PM 8626916 ER PT J AU FitzGerald, D Pastan, I AF FitzGerald, D Pastan, I TI Recombinant immunotoxins for the treatment of cancer SO JOURNAL OF CONTROLLED RELEASE LA English DT Article; Proceedings Paper CT 7th International Symposium on Recent Advances in Drug Delivery Systems CY FEB 27-MAR 02, 1995 CL SALT LAKE CITY, UT SP Baxter Healthcare Corp, Becton Dickinson & Co, Ciba Geigy Corp, Hoffmann La Roche Inc, MacroMed Inc, Marion Merrell Dow Inc, Pacific Corp, JAGO Pharma AG, Sam Yang Co Ltd, TheraTech Inc, Shiseido Res Ctr, 3M Pharm, Drug Delivery Syst, Jpjohn Co, Yamanouchi Pharm Co Ltd DE toxin; immunotoxin; cancer; receptor; ligand; antibody ID PSEUDOMONAS EXOTOXIN; NUCLEOTIDE-SEQUENCE; DIPHTHERIA-TOXIN; STRUCTURAL GENE; CHAIN; EXPRESSION; AERUGINOSA; RESOLUTION; 2.5-A AB The targeted delivery of protein toxins is presented as a novel approach for the treatment of human cancer. Bacterial or plant toxins are modified genetically to delete sequences that mediate binding to all cells, These sequences are replaced by cDNAs which encode binding ligands for receptors and antigens which are expressed selectively at high levels on the surface of cancer cells, Toxins that are modified in this way are termed immunotoxins or chimeric toxins. The immunotoxin-mediated antitumor activity in experimental rodent models is predictive of a favorable outcome for treating the corresponding human disease. RP FitzGerald, D (reprint author), NCI,MOLEC BIOL LAB,DIV CANC BIOL DIAG & CTR,NIH,BLDG 37-4B03,BETHESDA,MD 20892, USA. NR 19 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 J9 J CONTROL RELEASE JI J. Control. Release PD MAY PY 1996 VL 39 IS 2-3 BP 261 EP 265 DI 10.1016/0168-3659(95)00200-6 PG 5 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA UT432 UT WOS:A1996UT43200016 ER PT J AU Jaeger, RG Jaeger, MMM Araujo, VC Kachar, B AF Jaeger, RG Jaeger, MMM Araujo, VC Kachar, B TI Cytoskeletal distribution of vimentin in neoplastic myoepithelial cells. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDCD,NIH,EUA,BETHESDA,MD. RI Marques, Marcia/F-3780-2012; Araujo, Vera /G-3586-2014; Jaeger, Ruy/G-8230-2011 OI Marques, Marcia/0000-0002-9398-1252; NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAY PY 1996 VL 75 IS 5 BP 1099 EP 1099 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VG926 UT WOS:A1996VG92600310 ER PT J AU Nagler, R Katz, J Fox, PC Baum, BJ AF Nagler, R Katz, J Fox, PC Baum, BJ TI Irradiation induced alterations of the gene expression pattern in rat submandibular gland. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,NIH,BETHESDA,MD 20892. RAMBAM MED CTR,DEPT ORAL & MAXILLOFACIAL SURG,HAIFA,ISRAEL. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAY PY 1996 VL 75 IS 5 BP 1253 EP 1253 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VG926 UT WOS:A1996VG92601389 ER PT J AU Albandar, JM Brown, LJ Loe, H AF Albandar, JM Brown, LJ Loe, H TI Tooth loss over 6 years in adolescents with early onset periodontitis. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAY PY 1996 VL 75 IS 5 BP 1301 EP 1301 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VG926 UT WOS:A1996VG92601650 ER PT J AU Lujan, HD Mowatt, MR Nash, TE AF Lujan, HD Mowatt, MR Nash, TE TI Lipid requirements and lipid uptake by Giardia lamblia trophozoites in culture SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article DE bile; bile salts; cyclodextrin; intestine; lipid transfer; lipoprotein; parasite; protozoa ID LOW-DENSITY LIPOPROTEINS; SERUM-FREE MEDIUM; TRYPANOSOMA-BRUCEI; AXENIC CULTURE; BILE-SALTS; PROTEINS; BINDING; GROWTH; RECEPTORS; PARASITE AB To better understand the lipid requirements of Giardia lamblia trophozoites and the mechanisms of lipid uptake, we supplemented serum-free TYI-S-33 medium with lipids incorporated into different lipid carriers. We found that serum lipoproteins, beta-cyclodextrins, and bile salts are able to supply cholesterol and phospholipids to Giardia and to support the multiplication of the parasite in vitro. The growth rates obtained with different lipoproteins or bile salts and lipid mixtures were similar to that in standard culture medium containing serum. Pulse labelling experiments using fluorescent lipid analogs demonstrated that Giardia can take up lipids from lipoproteins, beta-cyclodextrins, or bile salt micelles, but with different kinetics, and that bile salts greatly facilitated lipid transfer from lipoproteins and cyclodextrins to the parasite surface. The binding of different radioiodinated lipoprotein classes to the trophozoite surface, inhibition of lipoprotein interiorization at 4 degrees C or by cytochalasin D, and incorporation studies using fluorescent LDL suggested that a small component of lipid uptake by trophozoites was likely due to endocytosis of lipoproteins. RP Lujan, HD (reprint author), NIAID,PARASIT DIS LAB,NIH,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 45 TC 33 Z9 33 U1 2 U2 2 PU SOC PROTOZOOLOGISTS PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD MAY-JUN PY 1996 VL 43 IS 3 BP 237 EP 242 DI 10.1111/j.1550-7408.1996.tb01398.x PG 6 WC Microbiology SC Microbiology GA UK823 UT WOS:A1996UK82300014 PM 8640194 ER PT J AU Topalian, SL Gonzales, MI Parkhurst, M Li, YF Southwood, S Sette, A Rosenberg, SA Robbins, PF AF Topalian, SL Gonzales, MI Parkhurst, M Li, YF Southwood, S Sette, A Rosenberg, SA Robbins, PF TI Melanoma-specific CD4(+) T cells recognize nonmutated HLA-DR-restricted tyrosinase epitopes SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID PEPTIDES; MOLECULES; SEQUENCE; ALLELES; ANTIGEN; HLA-DR1; MOTIF; CDNA AB Tyrosinase was the first melanoma-associated antigen shown to be recognized by CD4(+) T cells. In this study, we have identified two HLA-DRB1*0401-restricted peptides recognized by these T cells: Ty 56-70 and Ty 448-462. As with many of the MHC class I-restricted melanoma epitopes, both are nonmutated self peptides that have intermediate and weak MHC binding affinities, respectively. Mutated and truncated versions of these peptides were used to define their MHC binding anchor residues. Anchor residues were then modified to derive peptides with increased MHC binding affinities and T cell stimulatory properties. Ty 56-70 and Ty 448-462 enhance the list of immunogenic HLA-A2-, A24-, and B44-restricted tyrosinase peptides already described. Thus, tyrosinase provides a model for anti-melanoma vaccines in which a single molecule can generate multivalent immunization incorporating both CD4(+) and CD8(+) T cell. responses. C1 CYTEL CORP,SAN DIEGO,CA 92121. RP Topalian, SL (reprint author), NEI,NIH,SURG BRANCH,BLDG 10,RM 2B47,BETHESDA,MD 20892, USA. NR 32 TC 210 Z9 213 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 1 PY 1996 VL 183 IS 5 BP 1965 EP 1971 DI 10.1084/jem.183.5.1965 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UM424 UT WOS:A1996UM42400004 PM 8642306 ER PT J AU Schweighoer, E Fowlkes, BJ AF Schweighoer, E Fowlkes, BJ TI Positive selection is not required for thymic maturation of transgenic gamma delta T cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID LYMPHOCYTES-T; CLONAL DELETION; HEAT-SHOCK; RECEPTOR; RECOGNITION; ANTIGEN; MICE; SPECIFICITY; MOUSE; EXPRESSION AB Previously published reports describing thymic differentiation in two TCR gamma delta transgenic mouse models have suggested that gamma delta T cells require MHC-mediated positive selection to reach full maturity. Recent studies indicate that recognition of antigen by mature gamma 6 T cells is not MHC restricted, raising the issue of why developing gamma 6 T cells would even require MHC-driven positive selection. Therefore, we have reinvestigated the requirements for development and selection in G8 gamma delta T cell receptor (TCR) transgenic mice. Analyses of absolute cell numbers, phenotypic subsets, and functional competence of thymic and peripheral G8 gamma delta T cells indicate that these cells can fully mature in class I MHC-deficient mice. Moreover, mixed bone marrow chimeras demonstrate that gamma delta T cells of mutant Ba-microglobulin (beta 2M degrees) origin are partially deleted in the presence of H-2(d)-bearing thymocytes (previously believed to be the haplotype mediating positive selection). We conclude that there is no requirement for class I-like molecules for the maturation/development of these transgenic gamma delta T cells and that the differences in thymocyte phenotype and number observed are, instead, attributable to effects of clonal deletion. C1 NIAID,NIH,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892. NR 32 TC 57 Z9 57 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 1 PY 1996 VL 183 IS 5 BP 2033 EP 2041 DI 10.1084/jem.183.5.2033 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UM424 UT WOS:A1996UM42400012 PM 8642314 ER PT J AU Combadiere, B Freedman, M Chen, L Shores, EW Love, P Lenardo, MJ AF Combadiere, B Freedman, M Chen, L Shores, EW Love, P Lenardo, MJ TI Qualitative and quantitative contributions of the T cell receptor zeta chain to mature T cell apoptosis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ANTIGEN RECEPTOR; SIGNAL TRANSDUCTION; TYROSINE KINASE; CYTOPLASMIC TAIL; COMPLEX; ACTIVATION; PROTEIN; DEATH; INTERLEUKIN-2; MUTAGENESIS AB Engagement of the T cell receptor (TCR) of mature T lymphocytes can lead either to activation/proliferation responses or programmed cell death. To understand the molecular regulation of these two fundamentally different outcomes of TCR signaling, we investigated the participation of various components of the TCR-CD3 complex. We found that the TCR-zeta chain, while not absolutely required, was especially effective at promoting mature T cell apoptosis compared with the CD3 epsilon, gamma, or delta chains. We also carried out mutagenesis to address the role of the immunoreceptor tyrosine-based activation motifs (ITAMs) that are the principal signaling components found three times in the TCR-zeta chain and once in each of the CD3 epsilon, gamma, or delta chains. We found that the ability of the TCR-zeta chain to promote apoptosis results both from a quantitative effect of the presence of multiple ITAMs as well as qualitatively different contributions made by individual ITAMs. Apoptosis induced by single chain chimeras revealed that the first zeta ITAM stimulated greater apoptosis than the third zeta ITAM, and the second zeta ITAM was unable to trigger apoptosis. Because microheterogeneity in the amino acid sequence of the various ITAM motifs found in the TCR-zeta and CD3 chains predicts interactions with distinct src-homology-2-domain signaling proteins, our results suggest the possibility that individual ITAM motifs might play unique roles in TCR responses by engaging specific signaling pathways. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. NICHHD,NIH,LAB MAMMALIAN GENES & DEV,BETHESDA,MD 20892. RP Combadiere, B (reprint author), NIAID,NIH,IMMUNOL LAB,BLDG 10,BETHESDA,MD 20892, USA. RI Combadiere, Behazine/G-3881-2013 NR 45 TC 73 Z9 74 U1 1 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 1 PY 1996 VL 183 IS 5 BP 2109 EP 2117 DI 10.1084/jem.183.5.2109 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UM424 UT WOS:A1996UM42400019 PM 8642321 ER PT J AU DiRosa, F Matzinger, P AF DiRosa, F Matzinger, P TI Long-lasting CD8 T cell memory in the absence of CD4 T cells or B cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ANTIGEN-PRESENTING CELLS; TRANSPLANTATION TOLERANCE; DISTINCT PATHWAYS; LYMPHOCYTES-B; INDUCTION; INVIVO; MICE; MACROPHAGE; RESPONSES; STIMULATION AB The cellular basis of immunological memory has been a debated issue. It is not clear whether CD8 T cell memory is maintained by long-lived cells or by specific or nonspecific restimulation. Here, we have approached the question from a different angle, asking whether the cellular interactions that are required to maintain memory are the same as those necessary to activate cytotoxic T lymphocytes. We studied the CD8 memory response to the male antigen H-Y in mice deficient in CD4 cells or B cells and found that memory in these mice was virtually unimpaired. These results suggest that CD8 memory is CD4 independent and that there is no requirement for long ten retention of immune complexes on follicular dendritic cells, nor for B cells as antigen-presenting cells. C1 NIAID,NIH,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892. RI Di Rosa, Francesca/J-8116-2014 NR 56 TC 61 Z9 62 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 1 PY 1996 VL 183 IS 5 BP 2153 EP 2163 DI 10.1084/jem.183.5.2153 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UM424 UT WOS:A1996UM42400023 PM 8642325 ER PT J AU Vodovotz, Y Geiser, AG Chesler, L Letterio, J Campbell, A Lucia, MS Sporn, MB Roberts, AB AF Vodovotz, Y Geiser, AG Chesler, L Letterio, J Campbell, A Lucia, MS Sporn, MB Roberts, AB TI Spontaneously increased production of nitric oxide and aberrant expression of the inducible nitric oxide synthase in vivo in the transforming growth factor beta 1 null mouse SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID FACTOR-BETA-1; MACROPHAGES; CELLS AB Transforming growth factor beta 1 null mice (TGF-beta 1(-/-)) suffer from multifocal inflammation and die by 3-4 wk of age. In these mice, levels of nitric oxide (NO) reaction products in serum are elevated approximately fourfold over levels in controls, peaking at 15-17 d of life. Shortterm treatment of TGF-beta 1(-/-) mice with N-G-monomethyl-L-arginine suppressed this elevated production of NO. Expression of inducible NO synthase (iNOS) mRNA and protein is increased in the kidney and heart of TGF-beta 1(-/-) mice. These findings demonstrate that TGF-beta 1 negatively regulates iNOS expression in vivo, as had been inferred from mechanistic studies on the control of iNOS expression by TGF-beta 1 in vitro. RP Vodovotz, Y (reprint author), NIH,CHEMOPREVENT LAB,BLDG 41,ROOM C-629,BETHESDA,MD 20892, USA. NR 33 TC 86 Z9 88 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 1 PY 1996 VL 183 IS 5 BP 2337 EP 2342 DI 10.1084/jem.183.5.2337 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UM424 UT WOS:A1996UM42400040 PM 8642342 ER PT J AU Yao, ZB Maraskovsky, E Spriggs, MK Cohen, JI Armitage, RJ Alderson, MR AF Yao, ZB Maraskovsky, E Spriggs, MK Cohen, JI Armitage, RJ Alderson, MR TI Herpesvirus saimiri open reading frame 14, a protein encoded by a T lymphotropic herpesvirus, binds to MHC class II molecules and stimulates T cell proliferation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID B-CELLS; EXPRESSION; RESPONSES; RECEPTOR; GENOME; GENES AB Herpesvirus saimiri (HVS) is an oncogenic, lymphotropic, gamma-herpesvirus that transforms human and simian T cells in vitro and causes lymphomas and leukemias in various species of New World primates. Nucleotide sequence analysis of the HVS genome revealed an open reading frame with 22% amino acid identity to the mouse mammary tumor virus 7 superantigen, In this study, we demonstrate that this open reading frame, HVS14, encodes a heavily glycosylated protein that is secreted, Both the HVS14 present in the supernatant of transfected cells and a chimeric HVS14.Fc fusion protein were found to bind to heterodimeric MHC class II HLA-DR molecules, The supernatant from HVS14-transfected cells induced the proliferation of human PBMC, which could be specifically inhibited by HVS14-specific mAbs. Purified peripheral blood T cells were induced to proliferate in the presence of accessory cells and HVS14-containing supernatant, Whereas the HVS14 protein stimulated T cell proliferation, the HVS14.Fc fusion protein blocked proliferative responses to soluble Ags in vitro. Collectively, these data indicate that HVS14 can function as an immunomodulator that may contribute to the immunopathology of HVS infection. C1 IMMUNEX CORP,SEATTLE,WA 98101. NIH,CLIN INVEST LAB,BETHESDA,MD 20892. NR 21 TC 57 Z9 59 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1996 VL 156 IS 9 BP 3260 EP 3266 PG 7 WC Immunology SC Immunology GA UF742 UT WOS:A1996UF74200022 PM 8617948 ER PT J AU Rao, JB Chamberlain, RS Bronte, V Carroll, MW Irvine, KR Moss, B Rosenberg, SA Restifo, NP AF Rao, JB Chamberlain, RS Bronte, V Carroll, MW Irvine, KR Moss, B Rosenberg, SA Restifo, NP TI IL-12 is an effective adjuvant to recombinant vaccinia virus-based tumor vaccines - Enhancement by simultaneous B7-1 expression SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELLS; ANTIGEN; COSTIMULATION; ANTITUMOR; CD28 AB A number of cytokines and costimulatory molecules involved in immune activation have recently been identified including IL-12, a heterodimeric cytokine that supports the development of cell-mediated immunity, and B7-1, a costimulatory molecule involved in the activation of T lymphocytes, We explored the use of these immunomodulants as molecularly defined adjuvants in the function of recombinant anticancer vaccines using a murine model adenocarcinoma, CT26, transduced with a model Ag, beta-galactosidase (beta-gal), Although IL-12 given alone to mice bearing tumors established for 3 days did not have consistent antitumor activity, a profound therapeutic effect was observed when IL-12 administration was combined with a recombinant vaccinia virus (rVV) encoding beta-gal called VJS6. On the basis of the reported synergistic effects of IL-12 and the costimulatory molecule B7-1 (CD80) in vitro, we immunized mice with a double recombinant vaccinia encoding both the model tumor Ag and the costimulatory molecule B7-1, designated B7-1 beta-gal rVV. The adjuvant administration of IL-12 after immunization with this virus significantly enhanced survival in tumor-bearing animals, T cell subset depletions demonstrated that the in vivo activity of IL-12 was largely independent of CD4(+) T lymphocytes, whereas the in vivo activity of a B7-1 rVV required both CD4(+) and CD8(+) T cells to elicit maximal therapeutic effect, To our knowledge, this is the first description of B7-1 and IL-12 cooperation in vivo and represents a novel strategy to enhance the efficacy of recombinant anticancer vaccines. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NCI,HOWARD HUGHES MED INST,NIH,RES SCHOLARS PROGRAM,BETHESDA,MD 20892. NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01] NR 54 TC 116 Z9 116 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1996 VL 156 IS 9 BP 3357 EP 3365 PG 9 WC Immunology SC Immunology GA UF742 UT WOS:A1996UF74200035 PM 8617961 ER PT J AU Um, HD Orenstein, JM Wahl, SM AF Um, HD Orenstein, JM Wahl, SM TI Fas mediates apoptosis in human monocytes by a reactive oxygen intermediate dependent pathway SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; PROGRAMMED CELL-DEATH; MONOCLONAL-ANTIBODY; PROTEASE INHIBITORS; HYDROGEN-PEROXIDE; N-ACETYLCYSTEINE; CYTO-TOXICITY; FACTOR-ALPHA; T-CELLS; ANTIGEN AB Monocyte apoptosis has emerged as a central regulatory event in hemopoiesis and inflammation. Inflammatory cytokines can either promote or prevent monocyte apoptosis. To study the possible role of Fas Ag, a member of the TNF/nerve growth factor receptor family, in monocyte apoptosis, human peripheral blood monocytes activated by IL-1 beta or TNF-alpha were exposed to anti-fas mAb. Engagement of the Fas Ag resulted in apoptosis of monocytes, as monitored by propidium iodide uptake, decrease in cell size, DNA fragmentation, and characteristic ultrastructural changes. The apoptotic action of Fas was abolished completely by antioxidants such as N-acetylcysteine and glutathione, suggesting a role for reactive oxygen intermediates (ROI) in the death process. Consistent with this observation, Fas stimulation enhanced the fluorescence associated with oxidation of 2',7'-dichlorofluorescein, indicating increased levels of intracellular ROI. Moreover, the exogenous addition of hydrogen peroxide or menadione, an intracellular generator of superoxide anion, was sufficient for the induction of monocyte apoptosis. These data indicate that ROI are key mediators of Fas-induced apoptosis. In contrast to IL-1 beta and TNF-alpha LPS-treated monocytes were resistant to the apoptotic action of Fas. Under these conditions, LPS did not down-regulate Fas, but inhibited the Fas-dependent elevation of ROI. Therefore, monocytes appear to have a protective mechanism that can interfere directly with the Fas-induced pathway of cell suicide, thereby controlling their destiny. C1 NIDR,CELLULAR IMMUNOL SECT,IMMUNOL LAB,NATL INST HLTH,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,SCH MED,DEPT PATHOL,WASHINGTON,DC 20037. FU NIDCR NIH HHS [DE-12583] NR 58 TC 222 Z9 227 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1996 VL 156 IS 9 BP 3469 EP 3477 PG 9 WC Immunology SC Immunology GA UF742 UT WOS:A1996UF74200049 PM 8617975 ER PT J AU Goletti, D Kinter, AL Hardy, EC Poli, G Fauci, AS AF Goletti, D Kinter, AL Hardy, EC Poli, G Fauci, AS TI Modulation of endogenous IL-1 beta and IL-1 receptor antagonist results in opposing effects on HIV expression in chronically infected monocytic cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; PERIPHERAL-BLOOD MONOCYTES; LONG TERMINAL REPEAT; GROWTH-FACTOR-BETA; FACTOR-ALPHA; MONONUCLEAR-CELLS; HUMAN MACROPHAGES; CYTOKINE SECRETION; TYPE-1 EXPRESSION AB A proportion of HIV-infected individuals experience episodes of localized or systemic bacterial infections caused by Gramnegative bacteria. Many of the clinical side effects of these infections are associated with the production of proinflammatory cytokines, which are induced primarily by LPS, a constituent of the bacterial cell wall of Gram-negative bacteria. The present study examines the mechanisms involved in LPS-mediated induction of HIV expression in U1 cells, a promonocytic cell line chronically infected with HIV. Stimulation of U1 cells by LPS alone induced minimal levels of HIV expression, which was significantly enhanced by granulocyte-macrophage colony-stimulating factor (GM-CSF). Costimulation of U1 cells with LPS plus GM-CSF resulted in the accumulation of steady-state levels of HIV RNA; however, only a weak induction of HIV long terminal repeat-driven transcription, which was not associated with the activation of the cellular transcription factor nuclear factor-kappa B, was noted. Costimulation of cells with LPS plus GM-CSF induced the production of proinflammatory cytokines, IL-8, IL-1 beta and IL-6, but not TNF-alpha. IL-1 receptor antagonist (ra) inhibited LPS enhancement of HIV expression in GM-CSF-stimulated cells, suggesting that endogenous IL-1 was involved in LPS-mediated viral production. In this regard, anti-inflammatory cytokines inhibited LPS plus GM-CSF-stimulated HIV expression, and this effect closely correlated with inhibition of IL-1 beta release and, in particular, with up-regulation of endogenous IL-1ra production. Thus, the balance between an endogenously produced viral inducer (IL-1 beta) and an inhibitor (IL-1ra) may represent an important pathway leading to modulation of HIV expression from monocytic cells. C1 SAN RAFFAELE SCI INST,AIDS IMMUNOPATHOGENESIS UNIT,DIBIT,MILAN,ITALY. RP Goletti, D (reprint author), NIAID,IMMUNOREGULAT LAB,NATL INST HLTH,BLDG 10,RM 6A33,10 CTR DR,MSC-1576,BETHESDA,MD 20892, USA. OI Goletti, Delia/0000-0001-8360-4376 NR 56 TC 33 Z9 34 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1996 VL 156 IS 9 BP 3501 EP 3508 PG 8 WC Immunology SC Immunology GA UF742 UT WOS:A1996UF74200053 PM 8617979 ER PT J AU WojtowiczPraga, S Verma, UM Wakefield, L Esteban, JM Hartmann, D Mazumder, A AF WojtowiczPraga, S Verma, UM Wakefield, L Esteban, JM Hartmann, D Mazumder, A TI Modulation of B16 melanoma growth and metastasis by anti-transforming growth factor beta antibody and interleukin-2 SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE TGF beta; IL-2; immunosuppression; cytokines; cancer; melanoma; metastasis ID HUMAN BREAST-CANCER; LYMPHOCYTES; CELLS; TUMORIGENICITY; FACTOR-BETA-1; SECRETION; MICE AB Earlier evidence suggests that transforming growth factor beta (TGF beta) plays a significant role in tumor progression and metastasis. The most likely mechanism of the action of TGF beta is induction of immunosuppression in the host, allowing for unchecked tumor growth and metastasis. We attempted to test that hypothesis and to compare antitumor effects of anti-TGF beta antibody alone and in combination with interleukin-2 (IL-2). Six- to 8-week-old female C57B1-6 mice were induced with murine B16 melanoma by tail vein injection, Therapy was started 48 h after tumor injections. Monoclonal anti-TGF beta antibody (2G7) was administered intraperitoneally (i.p.) at 500 mu g every other day, and IL-2 at 10,000 U i.p. twice daily, for 21 days. A threefold decrease in the number of lesions in the anti-TGF beta/IL-2 treatment group compared with the control group was observed, a highly significant statistical difference (p = 0.002). No statistically significant differences were seen between the control group and other studied groups (IL-2 alone, anti-TGF beta alone). Analysis of TGF beta levels in plasma by the TGF beta-1 Quantikine assay indicated normal levels in the control and IL-2 groups, and significantly diminished levels in the two groups that received TGF beta antibody. However, acid-ethanol extraction of plasma (to reverse antibody binding before assay) showed normal plasma TGF beta levels in all groups, suggesting that the antibody may alter the availability of TGF beta in vivo. Microscopic analysis of metastases revealed a decrease in the average size of lesions in the groups treated with IL-2. Thus, combination therapy using anti-TGF beta antibody and IL-2 may be a novel, less toxic approach to tumor immunotherapy. C1 GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC CTR,DIV BONE MARROW TRANSPLANTAT,WASHINGTON,DC 20007. GEORGETOWN UNIV HOSP,DEPT PATHOL,WASHINGTON,DC 20007. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. RP WojtowiczPraga, S (reprint author), GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC CTR,DIV MED ONCOL,PODIUM LEVEL,WASHINGTON,DC 20007, USA. FU FDA HHS [FD-R-000776] NR 24 TC 45 Z9 52 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAY PY 1996 VL 19 IS 3 BP 169 EP 175 DI 10.1097/00002371-199605000-00001 PG 7 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA UU987 UT WOS:A1996UU98700001 PM 8811491 ER PT J AU Marincola, FM Hijazi, YM Fetsch, P Salgaller, ML Rivoltini, L Cormier, J Simonis, TB Duray, PH Herlyn, M Kawakami, Y Rosenberg, SA AF Marincola, FM Hijazi, YM Fetsch, P Salgaller, ML Rivoltini, L Cormier, J Simonis, TB Duray, PH Herlyn, M Kawakami, Y Rosenberg, SA TI Analysis of expression of the melanoma-associated antigens MART-1 and gp100 in metastatic melanoma cell lines and in in situ lesions SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE melanoma; MART-1; gp100; FNA ID TUMOR-INFILTRATING LYMPHOCYTES; HUMAN-MALIGNANT MELANOMA; AUTOLOGOUS MELANOMA; MESSENGER-RNA; IMMUNOTHERAPY; PROGRESSION; ESTABLISHMENT; RESTRICTION; RECOGNITION; CLONES AB MART-1 and gp100 melanoma associated antigens (MAA) are expressed by cells of the melanocytic lineage and are recognized by the majority of HLA-A2 restricted tumor-infiltrating lymphocytes. Heterogeneity of expression of MAA in tumor deposits may affect the natural history or response to therapy of patients with melanoma. In this study, we evaluated the expression of these MAA with a new monoclonal antibody (mAb) directed against MART-1 (M2-7C10) and the commercially available HMB45 mAb directed against gp100. Expression was tested in vitro by intracellular fluorescence analysis and in vivo by immunophenotyping of tissue specimens. Nine melanoma cell lines and 25 tissue specimens from metastatic melanoma were analyzed. One cell line did not express MART-I or gp100. The expression of both antigens was more heterogeneous and significantly reduced (p < 0.01) in mel melanoma cell lines compared with melanocytes, suggesting progressive loss of expression of MAA by neoplastic cells. None of the nonmelanoma cancer lines tested stained for MART-1 or gp100. Analysis of melanoma lesions by immunohistochemistry showed significant heterogeneity of expression of both MART-1 and gp100 MAA either as a percentage of cells expressing MAA or as intensity of expression. Ten of 25 frozen sections expressed MART-1 in < 50% of the cells. In 6 of 25 lesions, immunoreactivity for MART-1 was totally absent. Fine needle aspiration of metastatic lesions seemed to yield information accurately about amount and heterogeneity of expression of MAA in tumor lesions in vivo. Heterogeneity of expression of MAA may be one of several mechanisms leading to tumor escape from immune recognition, and pretreatment evaluation of tumor lesion for expression of these antigens may help in selecting patients best suited to antigen specific vaccine therapies. C1 NCI,DIV CLIN SCI,PATHOL LAB,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT TRANSFUS MED,BETHESDA,MD 20892. WISTAR INST ANAT & BIOL,DEPT ANAT,PHILADELPHIA,PA 19104. RP Marincola, FM (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B42,10 CTR DR,MSC 1502,BETHESDA,MD 20892, USA. RI Kawakami, Yutaka /E-7429-2013; OI Kawakami, Yutaka /0000-0003-4836-2855; Rivoltini, Licia/0000-0002-2409-6225 NR 49 TC 119 Z9 120 U1 0 U2 5 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAY PY 1996 VL 19 IS 3 BP 192 EP 205 DI 10.1097/00002371-199605000-00004 PG 14 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA UU987 UT WOS:A1996UU98700004 PM 8811494 ER PT J AU Landay, AL Clerici, M Hashemi, F Kessler, H Berzofsky, JA Shearer, GM AF Landay, AL Clerici, M Hashemi, F Kessler, H Berzofsky, JA Shearer, GM TI In vitro restoration of T cell immune function in human immunodeficiency virus-positive persons: Effects of interleukin (IL)-12 and anti-IL-10 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID INTERFERON-GAMMA-PRODUCTION; SEROPOSITIVE INDIVIDUALS; HIV; INFECTION; RECOGNITION; ACTIVATION; DEATH AB Cells from human immunodeficiency virus (HIV)-positive patients were evaluated for their in vitro responsiveness to recall antigen, alloantigen, and phytohemagglutinin (PHA) following the in vitro addition of interleukin (IL)-12 or anti-IL-10, Three-color flow cytometric analysis of CD4 and CD8 subsets was done to determine whether specific in vivo alterations in cell surface markers are associated with in vitro function changes, The results demonstrated a hierarchical response pattern to recall antigens versus alloantigen versus PHA, and these in vitro responses were associated with the number and activation status of CD4 cells. The in vitro addition of IL-12 or anti-IL-10 could restore antigen responses (HIV envelope peptides or influenza) in patients with 200-500 CD4 cells/mu L; however, in patients with <200 CD4 cells/mu L, this improved response was limited to the influenza response, Studies of this nature may provide important insights into the role of cytokines in the natural history of HIV disease, and they suggest that immune therapy of this type may be most effective in patients who have more preserved immune systems. C1 NCI,NIH,METAB BRANCH,BETHESDA,MD 20892. RUSH MED COLL,DEPT IMMUNOL MICROBIOL,CHICAGO,IL 60612. RUSH MED COLL,DEPT MED,CHICAGO,IL 60612. UNIV MILAN,CATTEDRA IMMUNOL,MILAN,ITALY. NR 28 TC 77 Z9 78 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1996 VL 173 IS 5 BP 1085 EP 1091 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UF867 UT WOS:A1996UF86700005 PM 8627058 ER PT J AU Brady, MT McGrath, N Brouwers, P Gelber, R Fowler, MG Yogev, R Hutton, N Bryson, YJ Mitchell, CD Fikrig, S Borkowsky, W Jimenez, E McSherry, G Rubinstein, A Wilfert, CM McIntosh, K Elkins, MM Weintrub, PS Bernstein, L Shliozberg, J Livingston, RA Vink, P Flautt, L Kline, MW Rayborn, T Kaul, A Lawrence, R Chandwani, S RubinHale, A KnoxBurke, K AlAttar, I Cooper, ER Pelton, SI Regan, AM Damon, B Young, B Nozyce, M Cihak, P Wiznia, A Chadwick, EG Silio, M Klauke, BJ Oleske, JM Colabelli, NB Connor, EM Gershon, A Pitt, J Shea, K Clark, P Cervia, JS Edelson, PJ SandersLaufer, D Hinds, GA Rakusan, TA Sever, J Herzog, K Ellaurie, M McKinney, RE Lane, BA Santacroce, S Nesheim, SR Sawyer, M Sarver, J Meadows, L Abrams, E Kanem, N Frere, M Urbano, R Ragni, MV Miller, B Carfagna, E Mendez, H Handlesman, E Difilippo, G Bergin, HF Shah, K Rao, S Villarica, NC Clintron, AA Hodes, D Barzelai, A Butler, L Heaton, S Gupta, A Ahern, L Munoz, J Li, K Bamji, M Kennedy, G Dummitt, M Pahwa, S Baksji, S Hunkler, JA Callaway, CC Crim, LB Diaz, C Rivera, C Flores, L Beauchamp, B Diaz, L Aguayo, R GarciaTrias, DE Frenkel, LD Gaur, S Scudder, RC Kechula, IM Lischner, HW Gregonis, SW Treston, CS Raphael, SA Carrer, MT Perez, L Berrios, Z Burchett, SK Melvin, AJ Corey, L Mohan, KM Grieco, M McKinley, G Rivera, J Moallen, H Schuller, G Pramberg, JC Alchediak, T VanDyke, RB Calligaro, D Church, J Deveikis, A Gilette, S Spector, SA Dankner, WM Instone, S Stangle, L Wara, DW Petru, A WilliamsHerman, D Baker, RC Siegel, R McOwen, N Robinson, J Wells, L Johnson, GM Rich, KC Hayani, K Turpin, D Sullivan, JL Luzuriaga, K Stechenberg, BW Robinson, JE Lim, W Dudek, V Mundorf, L Santucci, S Frenkel, L Lambert, JS Murante, B Scott, GB Gourley, J Mendoza, C Doyle, M Cantini, M AF Brady, MT McGrath, N Brouwers, P Gelber, R Fowler, MG Yogev, R Hutton, N Bryson, YJ Mitchell, CD Fikrig, S Borkowsky, W Jimenez, E McSherry, G Rubinstein, A Wilfert, CM McIntosh, K Elkins, MM Weintrub, PS Bernstein, L Shliozberg, J Livingston, RA Vink, P Flautt, L Kline, MW Rayborn, T Kaul, A Lawrence, R Chandwani, S RubinHale, A KnoxBurke, K AlAttar, I Cooper, ER Pelton, SI Regan, AM Damon, B Young, B Nozyce, M Cihak, P Wiznia, A Chadwick, EG Silio, M Klauke, BJ Oleske, JM Colabelli, NB Connor, EM Gershon, A Pitt, J Shea, K Clark, P Cervia, JS Edelson, PJ SandersLaufer, D Hinds, GA Rakusan, TA Sever, J Herzog, K Ellaurie, M McKinney, RE Lane, BA Santacroce, S Nesheim, SR Sawyer, M Sarver, J Meadows, L Abrams, E Kanem, N Frere, M Urbano, R Ragni, MV Miller, B Carfagna, E Mendez, H Handlesman, E Difilippo, G Bergin, HF Shah, K Rao, S Villarica, NC Clintron, AA Hodes, D Barzelai, A Butler, L Heaton, S Gupta, A Ahern, L Munoz, J Li, K Bamji, M Kennedy, G Dummitt, M Pahwa, S Baksji, S Hunkler, JA Callaway, CC Crim, LB Diaz, C Rivera, C Flores, L Beauchamp, B Diaz, L Aguayo, R GarciaTrias, DE Frenkel, LD Gaur, S Scudder, RC Kechula, IM Lischner, HW Gregonis, SW Treston, CS Raphael, SA Carrer, MT Perez, L Berrios, Z Burchett, SK Melvin, AJ Corey, L Mohan, KM Grieco, M McKinley, G Rivera, J Moallen, H Schuller, G Pramberg, JC Alchediak, T VanDyke, RB Calligaro, D Church, J Deveikis, A Gilette, S Spector, SA Dankner, WM Instone, S Stangle, L Wara, DW Petru, A WilliamsHerman, D Baker, RC Siegel, R McOwen, N Robinson, J Wells, L Johnson, GM Rich, KC Hayani, K Turpin, D Sullivan, JL Luzuriaga, K Stechenberg, BW Robinson, JE Lim, W Dudek, V Mundorf, L Santucci, S Frenkel, L Lambert, JS Murante, B Scott, GB Gourley, J Mendoza, C Doyle, M Cantini, M TI Randomized study of the tolerance and efficacy of high- versus low-dose zidovudine in human immunodeficiency virus-infected children with mild to moderate symptoms (AIDS Clinical Trials Group 128) SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNE-DEFICIENCY SYNDROME; CEREBROSPINAL-FLUID; ORAL ZIDOVUDINE; HIV INFECTION; AZT; ENCEPHALOPATHY; ABNORMALITIES; INFUSION; THERAPY; INFANTS AB The current dosage of zidovudine for children is 180 mg/m(2) every 6 h, To investigate whether a lower dosage was equally effective, human immunodeficiency virus (HIV)-infected children (3 months to 12 years) with mild to moderate symptoms were randomly assigned to receive either high-dose (180 mg/m(2)/dose) or low-dose (90 mg/m(2)/dose) zidovudine (double-blind), Treatments were compared with respect to neuropsychologic function, survival, clinical and laboratory evidence of disease progression, and safety and tolerance, Four hundred twenty-six HIV-infected children were enrolled; median time for receipt of study drug was 35 months, Zidovudine in either dose was well tolerated, with no difference in efficacy or tolerance by treatment group using any clinical or laboratory parameter, In children with mild to moderate disease, a reduction of zidovudine to 90 mg/m(2)/dose will result in substantial cost savings and should be the recommended dose. C1 OHIO STATE UNIV,COLL MED,DEPT PEDIAT & PREVENT MED,COLUMBUS,OH 43210. CHILDRENS HOSP,HIV PROGRAM,COLUMBUS,OH 43205. HARVARD UNIV,SCH MED,SCH PUBL HLTH,DANA FARBER CANC INST,STAT & DATA ANAL CTR,PED AI,BOSTON,MA. HARVARD UNIV,SCH MED,SCH PUBL HLTH,DANA FARBER CANC INST,DEPT PEDIAT BIOSTAT,BOSTON,MA. CHILDRENS HOSP,DIV INFECT DIS,BOSTON,MA. NCI,CLIN ONCOL PROGRAM,PEDIAT BRANCH,NEUROPSYCHOL GRP,BETHESDA,MD 20892. NIAID,DIV AIDS,PEDIAT MED BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD. CHILDRENS MEM HOSP,SECT PEDIAT & MATERNAL HIV INFECT,CHICAGO,IL 60614. UNIV CALIF LOS ANGELES,SCH MED,DEPT PEDIAT,LOS ANGELES,CA 90024. UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,SAN FRANCISCO,CA 94143. UNIV MIAMI,DEPT PEDIAT,MIAMI,FL 33152. SUNY HLTH SCI CTR,DEPT PEDIAT,BROOKLYN,NY 11203. NYU,DEPT PEDIAT,MED CTR,NEW YORK,NY 10016. ALBERT EINSTEIN COLL MED,DEPT PEDIAT,BRONX,NY 10467. ALBERT EINSTEIN COLL MED,DEPT MICROBIOL & IMMUNOL,BRONX,NY 10467. UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,CHILDRENS HOSP NEW JERSEY,DEPT CLIN PEDIAT,NEWARK,NJ 07103. DUKE UNIV,MED CTR,DEPT PEDIAT,DURHAM,NC 27706. BURROUGHS WELLCOME CO,RES TRIANGLE PK,NC 27709. SAN JUAN CITY HOSP,DEPT PEDIAT,GUAYNABO,PR. RI Oleske, James/C-1951-2016 OI Oleske, James/0000-0003-2305-5605 FU NIAID NIH HHS [AI-25924] NR 36 TC 33 Z9 34 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1996 VL 173 IS 5 BP 1097 EP 1106 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UF867 UT WOS:A1996UF86700007 PM 8627060 ER PT J AU Hagan, JB Bartemes, KR Kita, H Ottesen, EA Awadzi, K Nutman, TB Gleich, GJ AF Hagan, JB Bartemes, KR Kita, H Ottesen, EA Awadzi, K Nutman, TB Gleich, GJ TI Elevations in granulocyte-macrophage colony-stimulating factor and interleukin-5 levels precede posttreatment eosinophilia in onchocerciasis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CYTOKINE; IL-5; ANTIBODY AB The eosinophil survival assay was used to quantitate cytokines in 17 serial serum samples from 10 patients treated for onchocerciasis with diethylcarbamazine. Eosinophils isolated from normal donors were cultured for 4 days in the presence of patients' sera, and cell viability was determined, Serum specimens from 9 of 10 patients enhanced eosinophil survival from 4.8% +/- 2.2% (mean +/- SE) before treatment to 50.0% +/- 6.4% after treatment, Survival enhancement activity peaked before posttreatment eosinophilia. Antibodies to interleukin (IL)-5, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-3 were used to block cytokine activity in 22 serum samples. Antibodies to IL-5 blocked survival in 5 samples, antibodies to GM-CSF blocked survival in 6 samples, and a combination of antibodies to IL-5 and GM-CSF blocked survival in 8 additional samples, Overall, posttreatment sera from patients treated for onchocerciasis enhanced eosinophil survival; both GM-CSF and IL-5 may promote the posttreatment eosinophilia in filarial infection. C1 MAYO CLIN & MAYO FDN,DEPT IMMUNOL,ROCHESTER,MN 55905. MAYO CLIN & MAYO FDN,DEPT MED,ROCHESTER,MN 55905. ONCHOCERCIASIS CHEMOTHERAPY RES CTR,HOHOE,GHANA. NIAID,NIH,PARASIT DIS LAB,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-15231, AI-34486, AI-34577] NR 15 TC 7 Z9 7 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1996 VL 173 IS 5 BP 1277 EP 1280 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UF867 UT WOS:A1996UF86700033 PM 8627086 ER PT J AU Blauvelt, A Asada, H KlausKovtun, V Altman, DJ Lucey, DR Katz, SI AF Blauvelt, A Asada, H KlausKovtun, V Altman, DJ Lucey, DR Katz, SI TI Interleukin-15 mRNA is expressed by human keratinocytes, Langerhans cells, and blood-derived dendritic cells and is downregulated by ultraviolet B radiation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE cytokines; epidermis; Th1; RT-PCR ID GENE-EXPRESSION; INDUCTION; SIGNALS; LIGHT; UVB AB Interleukin (IL)-15 is a recently described cytokine that shares many functional activities with IL-2; however, unlike IL-2, IL-15 is produced by monocytes/macrophages, and not by lymphocytes. In this report, we assessed IL-15 mRNA expression by freshly isolated human epidermal cells, as well as by negatively selected keratinocytes and positively selected Langerhans cells, utilizing reverse transcription and polymerase chain reaction. In addition, cultured keratinocytes, immortalized keratinocytes (HaCaT cells), and dendritic cells expanded from adult peripheral blood in the presence of granulocyte/macrophage-colony stimulating factor and IL-4 were examined for IL-15 transcripts. Using cultured keratinocytes, we also studied the regulation of IL-15 mRNA expression by ultraviolet B radiation in vitro. Freshly isolated keratinocytes, HaCaT cells, and cultured keratinocytes all constitutively expressed IL-15 mRNA, and IL-15 expression was downregulated by ultraviolet B radiation in cultured keratinocytes in a time- and dose-dependent manner. In addition, IL-15 transcripts were constitutively expressed by freshly isolated Langerhans cells and by adult blood-derived dendritic cells. IL-15 produced by keratinocytes, Langerhans cells, and other tissue-specific dendritic cells may be important in attracting and activating antigen-specific Th1 T cells. Furthermore, ultraviolet B-induced downregulation of keratinocyte IL-15 production may contribute to the relative state of immunosuppression induced by sun exposure. C1 NATL CANC INST,EXPTL IMMUNOL BRANCH,BETHESDA,MD. RP Blauvelt, A (reprint author), NCI,DERMATOL BRANCH,BLDG 10,ROOM 12N238,10 CTR DR,MSC 1908,BETHESDA,MD 20892, USA. NR 34 TC 91 Z9 91 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 1996 VL 106 IS 5 BP 1047 EP 1052 DI 10.1111/1523-1747.ep12338641 PG 6 WC Dermatology SC Dermatology GA UJ131 UT WOS:A1996UJ13100016 PM 8618037 ER PT J AU Horne, MK Alkins, BR AF Horne, MK Alkins, BR TI Platelet binding of IgG from patients with heparin-induced thrombocytopenia SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID INVIVO RELEASE; FACTOR-4; ANTIBODIES; MEMBRANE; COMPLEX; FAB AB Although heparin induces immune-mediated thrombocytopenia, it has been difficult to demonstrate heparin specificity of the putative immunoglobin. Recently, however, a body of data has indicated that platelet factor 4 (PF4) is required for heparin-induced thrombocytopenia (HIT) antibody to bind to heparin. Using viable platelets in a physiologic buffer, we have now documented specific and reversible platelet binding of iodine 125-labeled IgG from 5 patients with HIT and binding of I-125-labeled F(ab')(2) from 2 of them. The binding requires the presence of both heparin and PF4 in a molar ratio of similar to 1:1. We have also shown that platelet activation increases HIT antibody binding. Our data suggest that the F(ab')(2) domain of HIT antibody binds to heparin-PF4 complexes that accumulate on the platelet surface when equimolar concentrations of heparin and PF4 are present. RP Horne, MK (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,HEMATOL SECT,RM 2C390,BLDG 10,BETHESDA,MD 20892, USA. NR 27 TC 32 Z9 32 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD MAY PY 1996 VL 127 IS 5 BP 435 EP 442 DI 10.1016/S0022-2143(96)90060-8 PG 8 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA UJ105 UT WOS:A1996UJ10500007 PM 8621980 ER PT J AU Sayers, TJ Lloyd, AR McVicar, DW OConnor, MD Kelly, JM Carter, CRD Wiltrout, TA Wiltrout, RH Smyth, MJ AF Sayers, TJ Lloyd, AR McVicar, DW OConnor, MD Kelly, JM Carter, CRD Wiltrout, TA Wiltrout, RH Smyth, MJ TI Cloning and expression of a second human natural killer cell granule tryptase, HNK-Tryp-2/granzyme 3 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE serine protease; T cells; cDNA ID CYTOLYTIC LYMPHOCYTES-T; PORE-FORMING PROTEIN; SERINE-PROTEASE; GRANZYME-A; PURIFICATION; FAMILY; GENE; ESTERASES; APOPTOSIS; SUBSTRATE AB Cytotoxic lymphocytes possess a number of serine proteases (granzymes) usually localized in cytoplasmic granules. To date, the DNA sequences of four human granzymes have been reported, A fifth human granzyme (granzyme 3) has been biochemically purified and its N-terminal amino acid sequence has been reported, This enzyme was described as possessing tryptase activity, cleaving synthetic substrates after arginine or lysine, We recently cloned a rat granzyme tryptase (RNK-Tryp-2), and used this cDNA to screen human cDNA libraries. Isolation of cDNA fragments of a human gene could be overlapped to provide a complete cDNA sequence, which we designated HNK-Tryp-2. The N-terminal amino acid sequence deduced from HNK-Tryp-2 was identical to that reported for granzyme 3, This gene appears to be a single copy gene that is expressed in isolated natural killer cells and T cells as well as in tissues containing these cells. C1 NCI,EXPTL IMMUNOL LAB,DIV BASIC SCI,FCRDC,FREDERICK,MD 21702. PRINCE HENRY HOSP,SYDNEY,NSW,AUSTRALIA. AUSTIN HOSP,AUSTIN RES INST,CELLULAR CYTOTOX LAB,HEIDELBERG,VIC 3084,AUSTRALIA. RP Sayers, TJ (reprint author), NCI,BCDP,SAIC FREDERICK,FCRDC,BLDG 560,RM 31-93,FREDERICK,MD 21702, USA. RI McVicar, Daniel/G-1970-2015; Sayers, Thomas/G-4859-2015; Smyth, Mark/H-8709-2014 OI Smyth, Mark/0000-0001-7098-7240 NR 31 TC 23 Z9 25 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAY PY 1996 VL 59 IS 5 BP 763 EP 768 PG 6 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA UN513 UT WOS:A1996UN51300021 PM 8656064 ER PT J AU Salustri, C AF Salustri, C TI Lack of magnetization transfer from the ferritin molecule SO JOURNAL OF MAGNETIC RESONANCE SERIES B LA English DT Article ID TRANSFER CONTRAST MTC; TISSUE C1 CNR,IST ELETTRON STATO SOLIDO,I-00156 ROME,ITALY. RP Salustri, C (reprint author), NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892, USA. NR 17 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1064-1866 J9 J MAGN RESON SER B JI J. Magn. Reson. Ser. B PD MAY PY 1996 VL 111 IS 2 BP 171 EP 173 DI 10.1006/jmrb.1996.0076 PG 3 WC Physics, Atomic, Molecular & Chemical SC Physics GA UK910 UT WOS:A1996UK91000008 PM 8661275 ER PT J AU Lamb, ME AF Lamb, ME TI Fatherless America: Confronting our most urgent social problem - Blankenhor,D SO JOURNAL OF MARRIAGE AND THE FAMILY LA English DT Book Review RP Lamb, ME (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 1 U2 3 PU NATL COUNC FAMILY RELATIONS PI MINNEAPOLIS PA 3989 CENTRAL AVE NE #550, MINNEAPOLIS, MN 55421 SN 0022-2445 J9 J MARRIAGE FAM JI J. Marriage Fam. PD MAY PY 1996 VL 58 IS 2 BP 526 EP 527 DI 10.2307/353515 PG 2 WC Family Studies; Sociology SC Family Studies; Sociology GA UR615 UT WOS:A1996UR61500023 ER PT J AU Chen, W Wetsel, W Steenbergen, C Murphy, E AF Chen, W Wetsel, W Steenbergen, C Murphy, E TI Effect of ischemic preconditioning and PKC activation on acidification during ischemia in rat heart SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE ischemia; reperfusion; preconditioning; protein kinase C; 4 beta-phorbol 12-myristate 13-acetate; 1,2-dioctanoyl-sn-glycerol ID PROTEIN-KINASE-C; MYOCARDIAL PROTECTION; ENERGY-METABOLISM; INTRACELLULAR PH; PHORBOL ESTERS; PHOSPHOLIPIDS AB Ischemic preconditioning (PC) has been shown to attenuate intracellular acidification during a subsequent period of ischemia, to minimize stunning, and to decrease infarct size. PKC activation has been suggested to be involved in this phenomenon. The present study is designed to test whether PKC activation could mimic and PKC inhibition could block the PC effects on intracellular acidification during ischemia and on stunning during reflow in Langendorff perfused rat hearts. Prior to 20 min of sustained global normothermic ischemia, groups of hearts were treated with the PKC activators 4 beta-phorbol 12-myristate 13-acetate (PMA) or 1,2-dioctanoyl-sn-glycerol (DOG), a group of hearts was treated with the PKC inhibitor chelerythrine (CH), a group was treated with DOG plus CH, a group was preconditioned with four cycles of 5 min of ischemia and 5 min of renew, and a group was treated with CH during PC. Recovery of left ventricular developed pressure (% of initial, pretreatment, preischemic LVDP), measured after 20 min of reflow, was improved in hearts treated with DOG. but not PMA (80 +/- 3% (DOG), 55 +/- 3% (PMA) v 51 +/- 3% (control), P<0.05 between DOG and control), although both caused a similar degree of PKC translocation (measured by fractionation followed by an assay of PKC activity using incorporation of P-32 into histone). The improved recovery of LVDP in the PC group and in the DOG group was blocked by chelerythrine. Measurement of pH (by P-31 NMR) showed that DOG reduced acidification at 15-20 min of ischemia, although the effect was not as great as PC, while PMA did not reduce acidification. The effect of DOG on pH(i) was attenuated by CH; however, the PC-induced attenuation of the fall in pH(i) was not affected by CH. High energy phosphates (measured by P-31 NMR) were not significantly different between any of the groups during ischemia or reflow. This study confirms that the protective effect of ischemic preconditioning on stunning in rat heart can be eliminated by inhibition of PKC, but suggests that the effect of PC on the fall in pH(i) during sustained ischemia is not mediated by PKC. (C) 1996 Academic Press Limited C1 NIEHS, CELLULAR & MOLEC PHARMACOL LAB, RES TRIANGLE PK, NC 27709 USA. DUKE UNIV, MED CTR, DEPT PATHOL, DURHAM, NC 27710 USA. RP Chen, W (reprint author), NIEHS, LAB MOLEC BIOPHYS, 4A-01, POB 12233, RES TRIANGLE PK, NC 27709 USA. FU NHLBI NIH HHS [R01 HL039752, HL 39752] NR 29 TC 39 Z9 39 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD MAY PY 1996 VL 28 IS 5 BP 871 EP 880 DI 10.1006/jmcc.1996.0082 PG 10 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA UM585 UT WOS:A1996UM58500007 PM 8762027 ER PT J AU McCormick, JL McKee, TC Cardellina, JH Boyd, MR AF McCormick, JL McKee, TC Cardellina, JH Boyd, MR TI HIV inhibitory natural products .26. Quinoline alkaloids from Euodia roxburghiana SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID REVERSE-TRANSCRIPTASE; LUNU-ANKENDA; ESCHERICHIA-COLI; MOSHER METHOD AB Bioassay-directed fractionation of the CH2Cl2-MeOH extract of Euodia roxburghiana resulted in the isolation of two known quinoline alkaloids, buchapine (1) and 2, and three new furoquinoline alkaloids, roxiamines A, B, and C (3-5). Compounds 1 and 2 protected CEM-SS cells from the cytopathic effects of HIV-1 in vitro (EC(50) 0.94 and 1.64 mu M, respectively), but 3-5 were inactive against HIV-1. C1 NCI,DIV CANC TREATMENT DIAGNOSIS & CTR,DEV THERAPEUT PROGRAM,LAB DRUG DISCOVERY RES & DEV,FREDERICK,MD 21702. NR 30 TC 74 Z9 75 U1 0 U2 5 PU AMER SOC PHARMACOGNOSY PI CINCINNATI PA LLOYD LIBRARY & MUSEUM 917 PLUM ST, CINCINNATI, OH 45202 SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD MAY PY 1996 VL 59 IS 5 BP 469 EP 471 DI 10.1021/np960250m PG 3 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA UR803 UT WOS:A1996UR80300002 PM 8778237 ER PT J AU Zheng, WH Fink, DW Guroff, G AF Zheng, WH Fink, DW Guroff, G TI Role of protein kinase C alpha in nerve growth factor-induced arachidonic acid release from PC12 cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE PC12 cells; nerve growth factor; arachidonic acid; protein kinase C ID SUPERIOR CERVICAL-GANGLIA; CANINE KIDNEY-CELLS; PHEOCHROMOCYTOMA CELLS; PHORBOL ESTERS; NEURITE OUTGROWTH; CHROMAFFIN CELLS; FACTOR INCREASES; FIBER OUTGROWTH; PKC ISOFORMS; PHOSPHORYLATION AB Nerve growth factor (NGF) increases arachidonic acid (AA) release by PC12 pheochromocytoma cells. To explore the role of protein kinase C (PKC) in this action of NGF, PKC was down-regulated by long-term treatment of the cells with phorbol 12-myristate 13-acetate (PMA). Such prolonged exposure to PMA (1 mu M) resulted in the inhibition of NGF-induced AA release. Moreover, pretreatment of PC12 cells with the protein kinase inhibitor staurosporine or with calphostin C, a specific inhibitor of PKC, also blocks the increase of AA release induced by NGF. These data, as well as that PMA alone can induce AA release in PC12 cells, suggest that PKC is necessary for NGF-induced AA release. Immunoblot analysis of whole cell lysates by using antibodies against various PKC isoforms revealed that our PC12 cells contained PKCs alpha, delta, epsilon, and zeta. PMA down-regulation depleted PKCs alpha, delta, and epsilon, and partially depleted zeta. To see which isoform was involved in NGF-induced AA release, an isoform-specific PKC inhibitor was used. GO 6976, a compound that inhibits PKCs alpha and beta specifically, blocked NGF-induced AA release. In addition, thymelea-toxin, a specific activator of PKCs alpha, beta, and gamma, induced AA release from PC12 cells in amounts comparable with those seen with NGF. Taken together, these data suggest that PKC a plays a role in NGF-induced AA release. C1 NICHHD, GROWTH FACTORS SECT, NIH, BETHESDA, MD 20892 USA. NR 59 TC 29 Z9 29 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 1996 VL 66 IS 5 BP 1868 EP 1875 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA UE776 UT WOS:A1996UE77600011 PM 8780012 ER PT J AU Vaughan, RA Brown, VL McCoy, MT Kuhar, MJ AF Vaughan, RA Brown, VL McCoy, MT Kuhar, MJ TI Species- and brain region-specific dopamine transporters: Immunological and glycosylation characteristics SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE dopamine uptake; cocaine receptor; photoaffinity labeling; immunoprecipitation; glycosylation ID NUCLEUS-ACCUMBENS; PREFRONTAL CORTEX; COCAINE RECEPTORS; MEDIAN-EMINENCE; RAT STRIATUM; CLONING; EXPRESSION; PROGRESS; BINDING; SITES AB Dopamine transporters (DATs) from the caudate nucleus of four species (rat, mouse, dog, and human) and four regions of rat brain (striatum, nucleus accumbens, prefrontal cortex, and midbrain) were photoaffinity labeled and analyzed by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis for cross-reactivity to four epitope-specific rat antipeptide antibodies. Each of these antibodies varied in its efficiency at recognizing DAT. The DATs from the rat brain regions exhibited the same degree of recognition by each of the four sera, a result compatible with these proteins being the product of a single gene. The DATs from the different species were recognized by all four sera but with different efficiencies, possibly relating to amino acid sequence differences within the immunizing epitope. All of the photolabeled, immunoprecipitated DATs migrated with a molecular mass of similar to 80 kDa, and no lower molecular mass forms were found. The DATs from all species and brain regions tested were shown by enzymatic deglycosylation to contain N-linked carbohydrates and sialic acids in amounts comparable with rat striatal DATs. The finding that no photolabeled DAT forms <80 kDa were isolated from membranes indicates that partially or incompletely glycosylated forms are not present, even in the midbrain cell bodies where immature forms might be expected to be found. These findings verify the utility of these anti-rat antibodies as biochemical tools for studying DATs from other species and extend our knowledge of biochemical characteristics of DATs from these species and brain regions. C1 MEHARRY MED COLL,DEPT PHARMACOL,NASHVILLE,TN 37208. RP Vaughan, RA (reprint author), NIDA,ADDICT RES CTR,NEUROSCI BRANCH,INTRAMURAL RES PROGRAM,POB 5180,BALTIMORE,MD 21224, USA. FU NIA NIH HHS [AG 05146] NR 44 TC 22 Z9 22 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 1996 VL 66 IS 5 BP 2146 EP 2152 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA UE776 UT WOS:A1996UE77600046 PM 8780047 ER PT J AU Baker, RA Herkenham, M Brady, LS AF Baker, RA Herkenham, M Brady, LS TI Effects of long-term treatment with antidepressant drugs on proopiomelanocortin and neuropeptide Y mRNA expression in the hypothalamic arcuate nucleus of rats SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE fluoxetine; imipramine; phenelzine; idazoxan; arcuate; NPY; POMC ID CORTICOTROPIN-RELEASING HORMONE; RECEPTOR MESSENGER-RNA; TYROSINE-HYDROXYLASE; GLUCOCORTICOID RECEPTOR; INSITU HYBRIDIZATION; CEREBROSPINAL-FLUID; THERAPEUTIC IMPLICATIONS; DEPRESSED-PATIENTS; BRAIN; IMMUNOREACTIVITY AB Antidepressant drugs have in common a delayed onset of clinical efficacy, In rats, long-term, daily administration of four different types of clinically effective antidepressant drugs results in decreased corticotropin releasing hormone (CRH) mRNA expression levels in the hypothalamic paraventricular nucleus (PVN), Because a subpopulation of neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus (Are) projects to the PVN, we measured NPY and POMC mRNA expression in the Are using in situ hybridization histochemistry at several time points following daily administration of four different antidepressant drugs, After 14 and 56 days of imipramine treatment. Are NPY mRNA levels are decreased to 85% and 75% of control levels, but are unchanged compared to control after one or five days of treatment, Are POMC mRNA levels are unchanged compared to controls at 1, 5, 14, or 56 days following imipramine treatment, Unlike after imipramine, Are NPY and POMC mRNA levels are increased significantly to 134-172% of control following 56-day treatment with the antidepressant drugs fluoxetine, phenelzine, or idazoxan, The divergent effects of imipramine vs the other 3 antidepressant drugs on Are NPY mRNA expression are similar to the pattern of changes in tyrosine hydroxylase (TH) mRNA expression levels in the locus coeruleus (LC) using the same experimental paradigm, but are different from the unidirectional depressive effects of all four drugs on CRH mRNA expression in the PVN, Thus, the Are NPY and LC noradrenergic systems may act coordinately in mediating antidepressant effects, The present data are consistent with the delayed onset of clinical efficacy for antidepressant drugs, and suggest that Are NPY and POMC neurotransmitter systems play a role in the pathophysiology of depression. C1 NIMH,FUNCT NEUROANAT SECT,BETHESDA,MD 20892. OI Herkenham, Miles/0000-0003-2228-4238 NR 50 TC 42 Z9 42 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD MAY PY 1996 VL 8 IS 5 BP 337 EP 343 DI 10.1046/j.1365-2826.1996.04422.x PG 7 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA UM682 UT WOS:A1996UM68200002 PM 8736433 ER PT J AU Farrer, RG Dalakas, MC Quarles, RH AF Farrer, RG Dalakas, MC Quarles, RH TI Multiple antibodies to nerve glycoconjugates in a patient with neuropathy and monoclonal IgA gammopathy SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE ganglioside; IgA gammopathy; myelin-associated glycoprotein (MAG); neuropathy; paraproteinemia; sulfate-glucuronyl paragloboside ID MYELIN-ASSOCIATED GLYCOPROTEIN; GUILLAIN-BARRE-SYNDROME; ANTI-MAG ANTIBODIES; DEMYELINATING POLYNEUROPATHY; UNDETERMINED SIGNIFICANCE; PERIPHERAL-NERVE; PARAPROTEINS; GANGLIOSIDES; GLYCOLIPIDS AB Several immunological abnormalities were found in a patient with mixed axonal and demyelinating neuropathy in association with a prominent monoclonal IgA lambda band in his serum. He had antibodies to the major LM1 ganglioside of human nerve that were restricted to the IgA class, but they were polyclonal and distinct from the major monoclonal IgA component. He also had a low level of a monoclonal IgM lambda antibody to the myelin-associated glycoprotein and sulfate-3-glucuronyl paragloboside that was not detected by routine immunofixation. The observations made on this complex patient, are presented in the context of emphasizing that immunological reactivities to neural antigens that are not due to the principal monoclonal antibody may be present in patients with neuropathy in association with gammopathy. C1 NINCDS, NIH,MED NEUROL BRANCH, CELLULAR & MOLEC NEUROBIOL LAB,MYELIN & BRAIN DEV, BETHESDA, MD 20892 USA. NINCDS, NIH, NEUROMUSCULAR DIS SECT, BETHESDA, MD 20892 USA. NR 26 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 EI 1872-8421 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD MAY PY 1996 VL 66 IS 1-2 BP 71 EP 76 DI 10.1016/0165-5728(96)00025-2 PG 6 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA UU725 UT WOS:A1996UU72500009 PM 8964916 ER PT J AU Stuber, A Martin, R Stone, LA Maloni, H McFarland, HF AF Stuber, A Martin, R Stone, LA Maloni, H McFarland, HF TI Expression pattern of activation and adhesion molecules on peripheral blood CD4(+) T-lymphocytes in relapsing-remitting multiple sclerosis patients: A serial analysis SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE multiple sclerosis; lymphocyte subsets; fluorescence activated cell sorting (FACS); magnetic resonance imaging (MRI) ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CELLS; MRI AB We studied the expression of various cell surface molecules (CD25, CD28, CD29, CD45RO, CD56, LFA-1, VLA-4) on peripheral blood CD4(+) T-cells in 6 relapsing-remitting multiple sclerosis (RR-MS) patients. Furthermore, changes in the expression pattern of these surface markers during intervals of increased disease activity, which was measured by gadolinium (Gd-DTPA) magnetic resonance imaging (MRI) were examined. Although several patients showed signs of increased disease activity during the observation period, this was not paralleled by a relevant change in the expression of these activation and adhesion molecules. C1 NINCDS,NIH,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. NR 16 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD MAY PY 1996 VL 66 IS 1-2 BP 147 EP 151 DI 10.1016/0165-5728(96)00026-4 PG 5 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA UU725 UT WOS:A1996UU72500018 PM 8964909 ER PT J AU Deuschl, G Toro, C Zeffiro, T Massaquoi, S Hallett, M AF Deuschl, G Toro, C Zeffiro, T Massaquoi, S Hallett, M TI Adaptation motor learning of arm movements in patients with cerebellar disease SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article DE motor learning; ballistic arm movements; cerebellum ID LESIONS AB Objective-To design a test of motor learning using arm movements in normal subjects and patients with cerebellar disease. Methods-Elbow angle was continuously displayed as a cursor (a dot) on a computer screen, and subjects made ballistic elbow flexion and extension movements to try to move the cursor between two targets on the screen. The relation between the arm movement and its visual feedback was changed, and the subjects reacted by adapting the amplitude of their movements in subsequent trials. Results-The consecutive errors showed exponential learning curves during adaptation, which were quantified by their steepness. Ten patients with isolated cerebellar or olivopontocerebellar degeneration had less steep learning curves than normal subjects, indicating a failure of adaptation motor learning in cerebellar disease. The results show that this test may be useful for the analysis of motor learning. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BETHESDA,MD. RI Deuschl, Gunther/A-7986-2010 NR 23 TC 50 Z9 51 U1 1 U2 4 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD MAY PY 1996 VL 60 IS 5 BP 515 EP 519 DI 10.1136/jnnp.60.5.515 PG 5 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA UJ915 UT WOS:A1996UJ91500008 PM 8778255 ER PT J AU Deuschl, G Toro, C VallsSole, J Hallett, M AF Deuschl, G Toro, C VallsSole, J Hallett, M TI Symptomatic and essential palatal tremor .3. Abnormal motor learning SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article DE palatal tremor; inferior olive; motor learning; cerebellar disease ID INFERIOR OLIVE; CEREBELLUM; MYOCLONUS; LESIONS AB Background-Palatal tremor is divided into symptomatic palatal tremor (SPT) and essential palatal tremor (EPT) on the basis of clinical features. The inferior olive seems to be abnormal in SPT, but not EPT. Because the inferior olive is likely to be involved in several types of motor learning, it is hypothesised that motor learning would be abnormal in patients with SPT, but not those with EPT. Methods-In six patients with SPT and four patients with EPT, two motor learning paradigms were studied-the classical conditioning of an acoustically elicited eyeblink with electrical supraorbital nerve shock and a test of adaptation of ballistic arm movements to a change of the gain. Results-Classical conditioning was impaired unilaterally or bilaterally in the patients with SPT, depending on whether they had unilateral or bilateral abnormalities of the inferior olives, except for the two least affected patients. All but one of the patients with EPT had normal conditioning. On the adaptation test of arm movements, most of the patients with SPT had impaired learning of the arm contralateral to the hypertrophied inferior olive, regardless of whether the abnormality was unilateral or bilateral, but all patients with EPT had normal results. Conclusions-In SPT pseudohypertrophy of the inferior olive leads to defective cerebellar function, whereas in EPT the inferior olive functions normally. C1 NINCDS,HUMAN MOTOR CONTROL SECT,MED NEUROL BRANCH,NIH,BETHESDA,MD. RI Deuschl, Gunther/A-7986-2010 NR 28 TC 20 Z9 20 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD MAY PY 1996 VL 60 IS 5 BP 520 EP 525 DI 10.1136/jnnp.60.5.520 PG 6 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA UJ915 UT WOS:A1996UJ91500009 PM 8778256 ER PT J AU Messing, A Galbreath, EJ Sijapati, KK Brenner, M AF Messing, A Galbreath, EJ Sijapati, KK Brenner, M TI Overexpression of GFAP in transgenic mice. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 UNIV WISCONSIN,MADISON,WI 53706. NIH,BETHESDA,MD 20892. 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 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1996 VL 55 IS 5 BP 59 EP 59 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA UK933 UT WOS:A1996UK93300071 ER PT J AU Suzuki, K Hoffmann, A Sandhoff, K Starr, CM Skop, E Sango, K Proia, RL AF Suzuki, K Hoffmann, A Sandhoff, K Starr, CM Skop, E Sango, K Proia, RL TI Mice totally deficient in beta-hexosaminidase alpha and beta subunits show an additional mucopolysaccharidosis phenotype. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 UNIV N CAROLINA,CHAPEL HILL,NC 27515. NIDDKD,GENET BIOCHEM BRANCH,NIH,BETHESDA,MD 20892. GLYKO,NOVATO,CA. UNIV BONN,INST ORGAN CHEM & BIOCHEM,W-5300 BONN,GERMANY. RI Proia, Richard/A-7908-2012 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 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1996 VL 55 IS 5 BP 62 EP 62 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA UK933 UT WOS:A1996UK93300074 ER PT J AU Parchi, P Capellari, S Sima, AAF DAmato, C McKeever, P Mikol, J Brion, S Brown, P Chen, SG Petersen, RB Gambetti, P AF Parchi, P Capellari, S Sima, AAF DAmato, C McKeever, P Mikol, J Brion, S Brown, P Chen, SG Petersen, RB Gambetti, P TI Creutzfeldt-Jakob disease (CJD) with 178(ASN) mutation in the prion protein gene: Neuropathological and molecular features. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. UNIV MICHIGAN,ANN ARBOR,MI 48109. UNIV PARIS 07,LARIBOISIERE HOSP,PARIS,FRANCE. NINCDS,NIH,BETHESDA,MD 20892. RI Petersen, Robert/B-5075-2011; capellari, sabina/F-5545-2012; Parchi, Piero/L-9833-2015 OI Petersen, Robert/0000-0002-3154-0072; 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 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1996 VL 55 IS 5 BP 121 EP 121 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA UK933 UT WOS:A1996UK93300133 ER PT J AU Holt, GR Softky, WR Koch, C Douglas, RJ AF Holt, GR Softky, WR Koch, C Douglas, RJ TI Comparison of discharge variability in vitro and in vivo in cat visual cortex neurons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID INTRINSIC FIRING PATTERNS; SYNAPTIC RESPONSES; ELECTROPHYSIOLOGICAL CHARACTERIZATION; NEOCORTICAL NEURONS; INTERSPIKE INTERVAL; BACKGROUND ACTIVITY; PYRAMIDAL CELLS; RECORDED INVIVO; CORTICAL-CELLS; MOTOR CORTEX AB 1. In neocortical slices, the majority of neurons fire quite regularly in response to constant current injections. But neurons in the intact animal fire irregularly in response to constant current injection as well as to visual stimuli. 2. To quantify this observation, we developed a new measure of variability, which compares only adjacent interspike intervals and is therefore less sensitive to rate variations than existing measures such as the coefficient of variation of interspike intervals. 3. We find that the variability of firing is much higher in cells of primary visual cortex in the anesthetized cat than in slice. The response to current injected from an intracellular electrode in vivo is also variable, but slightly more regular and less bursty than in response to visual stimuli. 4. Using a new technique for analyzing the variability of integrate-and-fire neurons, we prove that this behavior is consistent with a simple integrate-and-fire model receiving a large amount of synaptic background activity, but not with a noisy spiking mechanism. C1 UNIV ZURICH,ETH ZURICH,INST NEUROINFORMAT,CH-8006 ZURICH,SWITZERLAND. UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,CTR BIOL & MED SYST,LONDON,ENGLAND. NIH,MATH RES BRANCH,BETHESDA,MD 20814. RP Holt, GR (reprint author), CALTECH,COMPUTAT & NEURAL SYST PROGRAM 13974,PASADENA,CA 91125, USA. OI Koch, Christof/0000-0001-6482-8067 NR 51 TC 244 Z9 252 U1 1 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 1996 VL 75 IS 5 BP 1806 EP 1814 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA UK809 UT WOS:A1996UK80900003 PM 8734581 ER PT J AU Bertram, R Sherman, A Stanley, EF AF Bertram, R Sherman, A Stanley, EF TI Single-domain/bound calcium hypothesis of transmitter release and facilitation SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID SQUID GIANT SYNAPSE; FROG NEUROMUSCULAR-JUNCTION; MOTOR-NERVE TERMINALS; NEUROTRANSMITTER RELEASE; TIME COURSE; CHANNELS; SECRETION; DIFFUSION; CA-2+; DEPOLARIZATION AB 1. We describe a model of transmitter release that is based on the finding that release can be gated during the opening of individual Ca2+ channels, suggesting that the release site can be activated by the Ca2+ domain under a single channel. In this model each release site contains four independent Ca2+ binding sites or gates with unbinding kinetics graded from slow to fast and affinities ranging from high to low. All four gates must be bound for release to occur. Thus synaptic dynamics are governed by the kinetics of Ca2+ binding and unbinding from release sites, not Ca2+ diffusion. 2. Fast facilitation occurs when an action potential invades a terminal with one or more ions remaining bound to the release sites. Residual free Ca2+ is not necessary for facilitation with this mechanism, but if present it would enhance facilitation by binding to high-affinity gates between pulses. 3. This model can account for key features of release. These include fourth-power cooperativity with regard to external Ca2+; a release time course that is virtually independent of an increase in quantal content; an inverse relation between external Ca2+ and the degree of facilitation; and a steplike increase in facilitation with increasing stimulus frequency, with each step corresponding to a unitary decline in the Ca2+ cooperativity. 4. Facilitation of single-channel-based secretion is shown to be robust even if channel opening is stochastic. Spontaneous release of transmitter, assumed to be due in part to spontaneous Ca2+ channel openings, is shown to be elevated during and after a train of impulses. 5. An extension of the model to include multiple Ca2+ channels per release site demonstrates that one role of overlapping Ca2+ domains may be to accentuate depolarization-evoked release relative to spontaneous release. C1 NINCDS,SYNAPT MECHANISMS SECT,NIH,BETHESDA,MD 20892. RP Bertram, R (reprint author), NIDDKD,NIH,MATH RES BRANCH,BSA BLDG,SUITE 350,BETHESDA,MD 20814, USA. NR 53 TC 124 Z9 125 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 1996 VL 75 IS 5 BP 1919 EP 1931 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA UK809 UT WOS:A1996UK80900013 PM 8734591 ER PT J AU Liu, QY Schaffner, AE Li, YX Dunlap, V Barker, JL AF Liu, QY Schaffner, AE Li, YX Dunlap, V Barker, JL TI Upregulation of GABA(A) current by astrocytes in cultured embryonic rat hippocampal neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE GABA(A) receptor; ion channels; neuronal development; astrocyte; intracellular calcium; hippocampus; rat ID GAMMA-AMINOBUTYRIC ACID; SUBUNIT COMPOSITION; BRAIN ASTROCYTES; INTRACELLULAR CALCIUM; ACTIVATED CURRENTS; SODIUM-CHANNELS; SPINAL NEURONS; SCHWANN-CELLS; VOLTAGE-CLAMP; NERVE-FIBERS AB Embryonic rat hippocampal neurons were cultured on poly-D-lysine (PDL) or a monolayer of postnatal cortical astrocytes to reveal putative changes in neuronal physiology that involve astrocyte-derived signals during the first 4 d of culture. GABA-induced Cl- current (I-GABA) was quantified using outside-out and whole-cell patch-clamp recordings beginning at 30 min, when cells had become adherent. The amplitude and density (current normalized to membrane capacitance) of I-GABA in neurons grown on astrocytes became statistically greater than that recorded in neurons grown on PDL after 2 hr in culture (HIC). Although the current density remained unchanged in neurons on astrocytes, that in neurons on PDL decreased and became statistically lower beginning after 2 HIC. The differences in amplitude and density of I-GABA in the two groups of neurons were maintained during the 4 d experiment. The upregulation effect of astrocytes on neuronal I-GABA required intimate contact between the neuronal cell body and underlying astrocytes. Suppression of spontaneous Ca-c(2+) elevations in astrocytes by bis(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid that was loaded intracellularly decreased their modulatory effects on I-GABA. I-GABA in all cells was blocked completely by bicuculline and exhibited virtually identical affinity constants, Hill coefficients, and potentiation by diazepam in the two groups. Outside-out patch recordings revealed identical unitary properties of I-GABA in the two groups. More channels per unit of membrane area could explain the astrocyte enhancement of I-GABA. The results reveal that cortical astrocytes potentiate I-GABA in hippocampal neurons in a contact-dependent manner via a mechanism involving astrocyte Ca-c(2+) elevation. RP Liu, QY (reprint author), NINCDS, NEUROPHYSIOL LAB,NATL INST HLTH,BLDG 36,ROOM 2C02, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 54 TC 37 Z9 38 U1 1 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 1 PY 1996 VL 16 IS 9 BP 2912 EP 2923 PG 12 WC Neurosciences SC Neurosciences & Neurology GA UF711 UT WOS:A1996UF71100006 PM 8622122 ER PT J AU Chen, LTL Wise, SP AF Chen, LTL Wise, SP TI Evolution of directional preferences in the supplementary eye field during acquisition of conditional oculomotor associations SO JOURNAL OF NEUROSCIENCE LA English DT Article DE motor learning; frontal lobe; preferred direction; context dependency; supplementary eye field; spatial representation ID MOTOR CORTICAL ACTIVITY; DORSOMEDIAL FRONTAL-CORTEX; DIMENSIONAL ARM MOVEMENTS; ADJACENT CINGULATE CORTEX; SACCADE-RELATED ACTIVITY; NEURONAL-ACTIVITY; REACHING MOVEMENTS; VISUAL TARGETS; PREFRONTAL CORTEX; DRAWING MOVEMENTS AB We assessed the preferred directions (PDs) of supplementary eye field (SEF) neurons during conditional visuomotor learning. Monkeys learned to select one of four saccadic eye movements in response to a foveal instruction stimulus (IS). ISs were either familiar or novel. Each familiar IS reliably evoked one saccade: 7 degrees left, right, up, or down from the central fixation point. Novel ISs initially triggered virtually random responses among those four possibilities, but the monkeys ultimately learned to select the instructed saccade. As reported previously, activity rates on novel IS trials significantly changed during learning. Some of these cells (learning-dependent) also have significant modulation on familiar IS trials, but others (learning-selective) lack such activity. Of the former, the familiar IS activity can be either directionally selective or omnidirectional. For most neurons, PDs were apparent during all phases of learning, but they were rarely constant. Only infrequently did a neuron's PD for novel ISs closely match that for familiar ISs throughout the learning process. In directional learning-dependent cells, the PD usually reoriented near the end of learning to resemble that for familiar IS trials. In omnidirectional cells, initially evident PDs dissipated with learning, even as the cell became more strongly modulated. Learning-selective cells typically began with significant PDs. but became unmodulated as learning progressed. Our findings show a pervasive lability in SEF PDs that may reflect a flexible and rapid remapping between inputs and responses within the premotor cortical network. C1 NIMH,NEUROPHYSIOL LAB,POOLESVILLE,MD 20837. NR 68 TC 83 Z9 83 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 1 PY 1996 VL 16 IS 9 BP 3067 EP 3081 PG 15 WC Neurosciences SC Neurosciences & Neurology GA UF711 UT WOS:A1996UF71100020 PM 8622136 ER PT J AU DeLeon, M Welcher, AA Nahin, RH Liu, Y Ruda, MA Shooter, EM Molina, CA AF DeLeon, M Welcher, AA Nahin, RH Liu, Y Ruda, MA Shooter, EM Molina, CA TI Fatty acid binding protein is induced in neurons of the dorsal root ganglia after peripheral nerve injury SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE fatty acid binding protein; DRG neurons; peripheral nerve injury; DA11 protein ID GENE-EXPRESSION; SCIATIC-NERVE; APOLIPOPROTEIN-E; MYELIN PROTEIN; MESSENGER-RNA; REGENERATION; ISOFORMS; SEQUENCES; DISTINCT; TUBULIN AB Peripheral nerve trauma induces the expression of genes presumed to be involved in the process of nerve degeneration and repair, In the present study, an in vivo paradigm was employed to identify molecules which may have important roles in these processes, A cDNA library was constructed with RNA extracted from rat dorsal root ganglia (DRG) 3 days after a sciatic nerve crush, After differential hybridization to this library, several cDNAs were identified that encoded mRNAs that were upregulated in the DRG ipsilateral to the crush injury, as opposed to the contralateral or naive DRG, Approximately 0.15% of all the clones screened were found to be induced, This report presents the types of induced sequences identified and characterizes one of them, DA11, The 0.7 kb DA11 full length cDNA clone contains a 405 nucleotide open reading frame that encodes a putative protein of 15.2 kDa (135 amino acid residues) and is a member of the family of fatty acid binding proteins (FABP), The DA11 protein differs by one amino acid residue from the sequence of the C-FAPB protein and by eight residues from the sequence of mall, proteins found in rat and mouse skin, respectively, Northern and Western blot analyses showed that the DA11 mRNA and protein were induced in the injured DRG, Furthermore, studies using antibodies generated against DA11 found that the DA11-like immunoreactivity was more pronounced in the nuclei of neurons located in the DRG ipsilateral to the sciatic cut than those located in the contralateral DRG, The induction of DA11 mRNA and protein in DRG neurons suggests, for the first time, the involvement of a neuronal FABP in the process of degeneration and repair in the nervous system. (C) 1996 Wiley-Liss, Inc. C1 LOMA LINDA UNIV,CTR MOL BIOL & GENE THERAPY,LOMA LINDA,CA 92350. AMGEN INC,DEPT IMMUNOL,THOUSAND OAKS,CA 91320. STANFORD UNIV,SCH MED,DEPT NEUROBIOL,STANFORD,CA 94305. NIDR,NEUROBIOL & ANESTHESIOL BRANCH,NIH,BETHESDA,MD. RP DeLeon, M (reprint author), LOMA LINDA UNIV,DEPT PHYSIOL & PHARMACOL,LOMA LINDA,CA 92350, USA. RI De Leon, Marino/A-6922-2009 OI De Leon, Marino/0000-0001-6576-785X FU NICHD NIH HHS [HD03807]; NIGMS NIH HHS [GM11239]; NINDS NIH HHS [NS08443] NR 48 TC 53 Z9 54 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD MAY 1 PY 1996 VL 44 IS 3 BP 283 EP 292 PG 10 WC Neurosciences SC Neurosciences & Neurology GA UH533 UT WOS:A1996UH53300009 PM 8723767 ER PT J AU Musachio, JL Scheffel, U Stathis, M Villemagne, V Finley, P Horti, A Kimes, A London, ED DavilaGarcia, M Kellar, KJ Dannals, RF AF Musachio, JL Scheffel, U Stathis, M Villemagne, V Finley, P Horti, A Kimes, A London, ED DavilaGarcia, M Kellar, KJ Dannals, RF TI Synthesis of [I-125/I-123]-IPH: A radiolabeled analog of epibatidine for in vivo studies of nicotinic acetylcholine receptors. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NIDA,DIV INTRAMURAL RES,BALTIMORE,MD. GEORGETOWN UNIV,DEPT PHARMACOL,WASHINGTON,DC. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 12 EP 12 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500012 ER PT J AU John, CS Lim, BB Vilner, BJ Geyer, BC Bowen, WD AF John, CS Lim, BB Vilner, BJ Geyer, BC Bowen, WD TI Synthesis, in vitro and in vivo studies of radioiodinated arylethylenediamines (AED's): New sigma receptor probes. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 GEORGE WASHINGTON UNIV,WASHINGTON,DC. NIDDK,LMC,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 16 EP 16 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500016 ER PT J AU Carson, RE Kiesewetter, DO Fluck, S Jagoda, E Der, MG Herscovitch, P Eckelman, WC AF Carson, RE Kiesewetter, DO Fluck, S Jagoda, E Der, MG Herscovitch, P Eckelman, WC TI Kinetic analysis of a new muscarinic cholinergic ligand for PET: [F-18]fluoro-propyl-TZTP. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,PET DEPT,BETHESDA,MD 20892. 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 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 31 EP 31 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500031 ER PT J AU Horti, A Scheffel, U Dannals, RF Stathis, M Finley, PA Ravert, HT London, ED AF Horti, A Scheffel, U Dannals, RF Stathis, M Finley, PA Ravert, HT London, ED TI [18F]-(+/-)-exo-2-(2-fluoro-5-pyridyl)-7-azabicyclo[2.2.1]heptane, a radioligand for in vivo labeling and imaging of central nicotinic acetylcholine receptors. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIDA,INTRAMURAL RES PROGRAM,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DIV INTRAMURAL RES,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 33 EP 33 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500033 ER PT J AU Villemagne, VL Horti, A Scheffel, U Ravert, HT Finley, P London, ED Dannals, RF AF Villemagne, VL Horti, A Scheffel, U Ravert, HT Finley, P London, ED Dannals, RF TI Imaging nicotinic acetylcholine receptors in baboon brain by PET. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NIDA,INTRAMURAL RES PROGRAM,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 34 EP 34 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500034 ER PT J AU Park, SG Reynolds, JC BruckerDavis, F Whatley, M McEllin, K Maxted, D Robbins, J Weintraub, BD AF Park, SG Reynolds, JC BruckerDavis, F Whatley, M McEllin, K Maxted, D Robbins, J Weintraub, BD TI Iodine kinetics during I-131 scanning in patients with thyroid cancer: Comparison of studies with recombinant human TSH (RHTSH) vs hypothyroidism. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 DANKOOK UNIV,COLL MED,CHEONAN,SOUTH KOREA. NIH,BETHESDA,MD 20892. GENZYME INC,CAMBRIDGE,MA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 49 EP 49 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500049 ER PT J AU Kitsiou, AN Srinivsan, G Quyyumi, AA Bacharach, SL Summers, RM Dilsizian, V AF Kitsiou, AN Srinivsan, G Quyyumi, AA Bacharach, SL Summers, RM Dilsizian, V TI Stress-induced reversible and mild-moderate irreversible thallium defects: Are they equally accurate for predicting recovery of function after revascularization? SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 90 EP 90 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500090 ER PT J AU Yoo, TM Kim, IS Kobayashi, H Kim, MK Le, N Webber, KO Pastan, I Carrasquillo, JA Paik, CH AF Yoo, TM Kim, IS Kobayashi, H Kim, MK Le, N Webber, KO Pastan, I Carrasquillo, JA Paik, CH TI Use of Tc-99m MAG3-glycolate to radiolabel disulfide stabilized fragment (dsFv) of anti-Tac antibody (Ab) lowers renal uptake. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. 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 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 104 EP 104 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500104 ER PT J AU Buvat, I Bartlett, ML Srinivasan, G Jousse, F Kitsiou, AN Carson, JM Dilsizian, V Bacharach, SL AF Buvat, I Bartlett, ML Srinivasan, G Jousse, F Kitsiou, AN Carson, JM Dilsizian, V Bacharach, SL TI Can gated FDG PET assess LV function as well as gated bloodpool SPECT? SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. INSERM,U66,PARIS,FRANCE. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 148 EP 148 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500148 ER PT J AU Ernst, M Zametkin, A Matochik, J Pascuavalca, D Jons, P Hardy, K Hankerson, J Cohen, R AF Ernst, M Zametkin, A Matochik, J Pascuavalca, D Jons, P Hardy, K Hankerson, J Cohen, R TI Low dopamine activity in Lesch Nyhan disease. An 18-fluorodopa PET study. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 173 EP 173 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500173 ER PT J AU Srinivasan, G Kitsiou, AN Bacharach, SL Davis, CM AF Srinivasan, G Kitsiou, AN Bacharach, SL Davis, CM TI FDG cardiac SPECT versus PET: Relation to SPECT radionuclide angiography and thallium scintigraphy SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 229 EP 229 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500229 ER PT J AU Chakrabarti, M Panyutin, I Neumann, RD Carrasquillo, JA AF Chakrabarti, M Panyutin, I Neumann, RD Carrasquillo, JA TI Transfer of DNA into lymphoma cells by DNA-bound to T101-biotinylated-avidin-polylysine antibody complex. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,DEPT NUCL MED,BETHESDA,MD 20892. 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 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 237 EP 237 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500237 ER PT J AU Endres, CJ Carson, RE Kolachana, B Su, T Saunders, R Eckelman, WC Breier, A AF Endres, CJ Carson, RE Kolachana, B Su, T Saunders, R Eckelman, WC Breier, A TI Simultaneous modeling of [C-11]raclopride PET and dopamine microdialysis SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 CC & NIMH,NIH,PET DEPT,BETHESDA,MD. 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 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 298 EP 298 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500298 ER PT J AU Esposito, G Kirkby, BS VanHorn, JD Ostrem, JL Weinberger, DR Berman, KF AF Esposito, G Kirkby, BS VanHorn, JD Ostrem, JL Weinberger, DR Berman, KF TI Different pathophysiological mechanisms of impaired Wisconsin Card Sorting in elderly normal subjects and schizophrenics studied with PET. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIMH,CBDB,UNIT PET,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 308 EP 308 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500308 ER PT J AU Bartlett, ML Srinivasan, G Jousse, F Carson, JM Dilsizian, V Bacharach, SL AF Bartlett, ML Srinivasan, G Jousse, F Carson, JM Dilsizian, V Bacharach, SL TI Quantitative regional analysis of SPECT gated blood pool images. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 362 EP 362 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500362 ER PT J AU Freedman, NMT Aloj, L DaubeWitherspoon, ME Carson, RE Danforth, DN Bacharach, SL AF Freedman, NMT Aloj, L DaubeWitherspoon, ME Carson, RE Danforth, DN Bacharach, SL TI Comparison of sensitivity for prone and supine breast imaging in PET and SPECT. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 0 Z9 0 U1 0 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 388 EP 388 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500388 ER PT J AU Lammertsma, AA Turjanski, N Hume, SP Luthra, SK Osman, S Piccini, P Brown, DJ Carroll, FI Brooks, DJ AF Lammertsma, AA Turjanski, N Hume, SP Luthra, SK Osman, S Piccini, P Brown, DJ Carroll, FI Brooks, DJ TI Quantification of dopamine transporter studies using carbon-11 labelled RTI-121 and PET. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,MRC,CSC,CYCLOTRON UNIT,LONDON W12 0HS,ENGLAND. NIDA,ADDICT RES CTR,NEUROSCI BRANCH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 426 EP 426 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500426 ER PT J AU Aloj, L Jagoda, E Lang, L Neumann, RD Eckelman, WC AF Aloj, L Jagoda, E Lang, L Neumann, RD Eckelman, WC TI Biodistribution of human transferrin radiolabeled with N-succinimidyl 4-[F-18] (fluoromethyl) benzoate in nude mice tumor models. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,DEPT NUCL MED,CTR CLIN,BETHESDA,MD 20892. NIH,PET DEPT,CTR CLIN,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 463 EP 463 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500463 ER PT J AU Kobayashi, H Yoo, TM Kim, IS Kim, MK Le, N Webber, KO Pastan, I Paik, CH Eckelman, WC Carrasquillo, JA AF Kobayashi, H Yoo, TM Kim, IS Kim, MK Le, N Webber, KO Pastan, I Paik, CH Eckelman, WC Carrasquillo, JA TI Favorable effect of lysine on biodistribution and metabolism of Tc-99m dsFv. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. 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 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 507 EP 507 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500507 ER PT J AU Lee, KS Jones, DW Gorey, JG Coppola, RC Knable, MB Heinz, A Porter, JK He, XS deCosta, BR Rice, KC Weinberger, DR AF Lee, KS Jones, DW Gorey, JG Coppola, RC Knable, MB Heinz, A Porter, JK He, XS deCosta, BR Rice, KC Weinberger, DR TI A kit formulation to prepare (R,S)-[I-123]IQNB for SPECT imaging of muscarinic receptors. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. NIDDKD,NEUROSCI LAB,BETHESDA,MD 20892. NIMH,CBDB,NEUROSCI CTR ST ELIZABETHS,WASHINGTON,DC. NORD INT INC,VANCOUVER,BC,CANADA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 630 EP 630 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500563 ER PT J AU Wu, C Jagoda, E Brechbiel, M Webber, KO Pastan, I Gansow, O Eckelman, WC AF Wu, C Jagoda, E Brechbiel, M Webber, KO Pastan, I Gansow, O Eckelman, WC TI The biodistribution and catabolism of Ga-67 labeled antitac DSFV fragment. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NIH,PET DEPT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 669 EP 669 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500602 ER PT J AU Jousse, F Srinivasan, G Carson, JM Dilsizian, V Bacharach, SL AF Jousse, F Srinivasan, G Carson, JM Dilsizian, V Bacharach, SL TI Effect of shortaxis angle selection on quantitation of myocardial uptake. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 699 EP 699 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500632 ER PT J AU Buvat, I Kitsiou, AN Srinivasan, G Dilsizian, V Bacharach, SL AF Buvat, I Kitsiou, AN Srinivasan, G Dilsizian, V Bacharach, SL TI Relationship between metabolism and function in CAD patients using gated FDG pet SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. INSERM,U66,PARIS,FRANCE. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 705 EP 705 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500638 ER PT J AU Price, JC Bacharach, SL Freedman, N Carson, RE AF Price, JC Bacharach, SL Freedman, N Carson, RE TI Noise reduction in PET attenuation correction by maximum likelihood histogram sharpening of attenuation images SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE PET transmission noise; noise reduction; attenuation histogram; fluorine-18-FDG ID POSITRON EMISSION TOMOGRAPHY; COMPUTED-TOMOGRAPHY AB A new method for PET transmission data processing was developed and found to reduce transmission noise in F-18-FDG cardiac emission images, This method is based on a model that describes the measured attenuation image histogram as some unknown true underlying histogram, blurred by noise, Methods: Emission data from an elliptical phantom (cardiac insert) and three humans were reconstructed using transmission data of varying duration with varying levels of smoothing, Biases and noise levels (cardiac sector analysis) were evaluated for the phantom (simulated replicates) and human emission images, Results: The estimated attenuation histograms typically displayed three distinct peaks corresponding to air, lung and soft tissue without a priori assumptions of the underlying mu values, This method effectively sharpened the histogram peaks and performed well for the phantom and human data. For intermediate transmission noise levels, biases in the phantom sector values were <4%, The human sector results were more variable but consistent with the phantom results, Noise reduction (similar to 30%) was demonstrated across all smooth levels for the phantom data. Conclusion: This histogram sharpening method introduces only small bias in the cardiac sector values while achieving an increase in effective transmission scan time of 50-100%, Alternatively, histogram sharpening permits less transmission data smoothing without increased noise. C1 NIH,PET DEPT,BETHESDA,MD 20892. NIH,DEPT NUCL MED,BETHESDA,MD 20892. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 15 TC 3 Z9 3 U1 0 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 BP 786 EP 794 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UK883 UT WOS:A1996UK88300025 PM 8965146 ER PT J AU Lee, KS Jones, DW Gorey, JG Coppola, RC Knable, MB Heinz, A He, XS deCosta, BR Rice, KC Weinberger, DR AF Lee, KS Jones, DW Gorey, JG Coppola, RC Knable, MB Heinz, A He, XS deCosta, BR Rice, KC Weinberger, DR TI Determination of the optimum pH for high radioiodination yields from stannylated precursors. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIMH,CTR NEUROSCI,CBDB,WASHINGTON,DC 20032. NIDDKD,MED CHEM LAB,NIH,BETHESDA,MD 20892. NIDDKD,NEUROSCI LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 856 EP 856 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500743 ER PT J AU Horti, AG Ravert, HT Mathews, WB Musachio, JL Kimes, A London, ED Dannals, RF AF Horti, AG Ravert, HT Mathews, WB Musachio, JL Kimes, A London, ED Dannals, RF TI Synthesis of high specific activity carbon-11 N-methylated analogs of epibatidine for imaging NAChRs. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIDA,DIV INTRAMURAL RES,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 878 EP 878 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500764 ER PT J AU Chakrabarti, M Le, N Paik, CH Carrasquillo, JA AF Chakrabarti, M Le, N Paik, CH Carrasquillo, JA TI Preparation of [I-125]-5-iododeoxyuridine (IUDR)-T101 and conjugates. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,DEPT NUCL MED,BETHESDA,MD 20892. 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 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 898 EP 898 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500784 ER PT J AU Bi, Z Lang, L Jagoda, E Williams, D Hankins, D Shapiro, S Eckelman, WC AF Bi, Z Lang, L Jagoda, E Williams, D Hankins, D Shapiro, S Eckelman, WC TI The development of growth factors as diagnostic and therapeutic radiopharmaceuticals. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,PET DEPT,BETHESDA,MD 20892. PROED INC,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 899 EP 899 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500785 ER PT J AU Caraco, C Aloj, L Lastoria, S Eckelman, WC AF Caraco, C Aloj, L Lastoria, S Eckelman, WC TI The gallium-deferoxamine complex: Stability with different deferoxamine concentrations and incubation conditions. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,PET DEPT,BETHESDA,MD 20892. NIH,DEPT NUCL MED,BETHESDA,MD 20892. INT,NAPLES,ITALY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 909 EP 909 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500795 ER PT J AU Horti, A Scheffel, U Dannals, RF Stathis, M Finley, PA Ravert, HT London, ED AF Horti, A Scheffel, U Dannals, RF Stathis, M Finley, PA Ravert, HT London, ED TI [18F]-(+/-)-exo-2-(2-fluoro-5-pyridyl)-7-azabicyclo [2.2.1]heptane, a radioligand for in vivo labeling and imaging of central nicotinic acetylcholine receptors. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIDA,DIV INTRAMURAL RES,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,DIV NUCL MED,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 919 EP 919 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500805 ER PT J AU Kobayashi, H Yoo, TM Kim, MK Kim, IS Le, N Webber, KO Pastan, I Eckelman, WC Paik, CH Carrasquillo, JA AF Kobayashi, H Yoo, TM Kim, MK Kim, IS Le, N Webber, KO Pastan, I Eckelman, WC Paik, CH Carrasquillo, JA TI Pharmacokinetics of L-lysine: Effect on I-125 anti-Tac dsFv antibody accumulation in the kidney. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. 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 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 926 EP 926 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500812 ER PT J AU Aloj, L Carson, RE Lang, L Herscovitch, P Eckelman, WC AF Aloj, L Carson, RE Lang, L Herscovitch, P Eckelman, WC TI Measurement of transferrin receptor kinetics in the liver using dynamic 3D-PET and [F-18]holo-transferrin. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,DEPT NUCL MED,BETHESDA,MD 20892. NIH,PET DEPT,BETHESDA,MD 20892. 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 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 928 EP 928 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500814 ER PT J AU Schmall, B Lang, L Jagoda, E Channing, M Sassaman, M Eckelman, WC AF Schmall, B Lang, L Jagoda, E Channing, M Sassaman, M Eckelman, WC TI Antagonists for 5HT1A and 5HT2A receptors. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,DEPT NUCL MED,BETHESDA,MD 20892. NIH,PET DEPT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 929 EP 929 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500815 ER PT J AU Jagoda, E Aloj, L Seidel, J Lang, L Moody, T Green, MV Eckelman, WC AF Jagoda, E Aloj, L Seidel, J Lang, L Moody, T Green, MV Eckelman, WC TI The evaluation of biochemical markers for cancer. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NCI,DEPT NUCL MED,NIH,BETHESDA,MD 20892. NCI,PET DEPT,NIH,BETHESDA,MD 20892. NCI,BPRP,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 930 EP 930 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500816 ER PT J AU Lang, L Jagoda, E Webber, KO Pastan, I Eckelman, WC AF Lang, L Jagoda, E Webber, KO Pastan, I Eckelman, WC TI ''Hydrolyzable'' linkers with 4-[F-18]fluorobenzoyl (FB) anti-Tac dsFv fragment. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,PED DEPT,BETHESDA,MD 20892. NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 931 EP 931 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500817 ER PT J AU John, CS Venugopal, R Li, J Bowen, WD Varma, VM Thakur, ML AF John, CS Venugopal, R Li, J Bowen, WD Varma, VM Thakur, ML TI Characterization and targeting of sigma receptor binding sites in human prostate tumor cells. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 GEORGE WASHINGTON UNIV,WASHINGTON,DC. NIDDK,LMC,NIH,BETHESDA,MD. NR 0 TC 1 Z9 1 U1 1 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 933 EP 933 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500819 ER PT J AU SurovaTrojanova, H Barker, C Carrasquillo, JA Bacharach, SL AF SurovaTrojanova, H Barker, C Carrasquillo, JA Bacharach, SL TI Influence of improper attenuation/emission registration of the accuracy of SPECT tumor imaging. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. 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 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 959 EP 959 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500845 ER PT J AU Sedelnikova, OA Neumann, RD Panyutin, IG AF Sedelnikova, OA Neumann, RD Panyutin, IG TI Radiotoxicity of iodine-125 labeled oligodeoxyribonucleotides in mammalian cells. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,DEPT NUCL MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 1029 EP 1029 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500915 ER PT J AU Herscovitch, P Doudet, D Channing, MA Carson, RE AF Herscovitch, P Doudet, D Channing, MA Carson, RE TI Determination of radiation dose estimates for PET radiopharmaceuticals using non-human primates: Application to C-11 arachidonic acid. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. 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 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 1036 EP 1036 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500922 ER PT J AU Geselowitz, DA Neumann, RD AF Geselowitz, DA Neumann, RD TI Site specific detection of DNA single-strand breaks from 16 alpha-[I-125]-iodo-3,17 beta-estradiol in MCF7 cells. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,DEPT NUCL MED,CTR CLIN,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 1049 EP 1049 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500935 ER PT J AU Carrasquillo, JA White, JD Paik, CH Le, N Rotman, M Goldman, CK Brechbiel, MW Gansow, OA Top, LE Reynolds, JC Nelson, DL Waldmann, TA AF Carrasquillo, JA White, JD Paik, CH Le, N Rotman, M Goldman, CK Brechbiel, MW Gansow, OA Top, LE Reynolds, JC Nelson, DL Waldmann, TA TI Biodistribution of In-111 vs Y-90 labeled anti-Tac monoclonal antibody. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 1055 EP 1055 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500941 ER PT J AU Mariani, G Lasku, A Villa, G Motta, C Calcagno, G Taddei, G Balza, E Gaggero, B Dorcaratto, A Pau, A Epenetos, A Zardi, L Viale, G AF Mariani, G Lasku, A Villa, G Motta, C Calcagno, G Taddei, G Balza, E Gaggero, B Dorcaratto, A Pau, A Epenetos, A Zardi, L Viale, G TI Validation in animal models and in patients of monoclonal antibody BC-1 directed against onco-fetal fibronectin - A marker of angiogenesis. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 UNIV GENOA,NUCL MED SERV,DIMI,GENOA,ITALY. UNIV GENOA,INST NEUROSURG,GENOA,ITALY. NATL CANC INST,GENOA,ITALY. IMPERIAL CANC RES FUND,LONDON WC2A 3PX,ENGLAND. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 1070 EP 1070 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500956 ER PT J AU Freedman, NMT Andrich, MP Choyke, P Fraker, D Bacharach, SL AF Freedman, NMT Andrich, MP Choyke, P Fraker, D Bacharach, SL TI Discordance between FDG PET and MRI scans of liver metastases pre and post therapy. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 1135 EP 1135 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62501021 ER PT J AU Aloj, L Caraco, C Jagoda, E Moody, T Eckelman, WC Neumann, RD AF Aloj, L Caraco, C Jagoda, E Moody, T Eckelman, WC Neumann, RD TI Facilitative and sodium dependent glucose transporter mRNA expression in nude mice tumor xenografts: Correlation with deoxyglucose uptake. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NCI,DEPT NUCL MED,BETHESDA,MD. NCI,PET DEPT,CTR CLIN,BETHESDA,MD. NCI,BPRB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 1140 EP 1140 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62501026 ER PT J AU John, CS Vilner, BJ Schwartz, AM Bowen, WD AF John, CS Vilner, BJ Schwartz, AM Bowen, WD TI Characterization of sigma receptor binding sites in human biopsied solid breast tumors. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 GEORGE WASHINGTON UNIV,DEPT RADIOL,WASHINGTON,DC. GEORGE WASHINGTON UNIV,DEPT PATHOL,WASHINGTON,DC. NIDDK,MED CHEM LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 1194 EP 1194 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62501080 ER PT J AU Yokoi, F Finley, P Stathis, M Chen, A Yaster, M Scheffel, U London, ED Wong, DF AF Yokoi, F Finley, P Stathis, M Chen, A Yaster, M Scheffel, U London, ED Wong, DF TI Effects of saffan and isoflurane on [H3]raclopride and [H3] NMSP binding in mouse brain. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 1245 EP 1245 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62501131 ER PT J AU Kapp, OH Siemion, J Eckelman, WC Reba, RC AF Kapp, OH Siemion, J Eckelman, WC Reba, RC TI Modeling of muscarinic receptor-ligand binding. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 UNIV CHICAGO,CHICAGO,IL 60637. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 1248 EP 1248 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62501134 ER PT J AU Heinz, A Jones, DW Gorey, JG Lee, KS Saunders, RC Knable, MB Weinberger, DR AF Heinz, A Jones, DW Gorey, JG Lee, KS Saunders, RC Knable, MB Weinberger, DR TI [I-123]beta-CIT and [I-123]IBZM SPECT of rhesus monkeys with neonatal and adult lesions of the amygdala-hippocampus: Effect on striatal dopaminergic neurons. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,CBDB,WASHINGTON,DC 20032. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 1257 EP 1257 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62501143 ER PT J AU Berman, KF AustinLane, JL Esposito, G VanHorn, JD Weinberger, DR AF Berman, KF AustinLane, JL Esposito, G VanHorn, JD Weinberger, DR TI Neurophysiological and neuropsychological dissection of the ''working'' and the ''memory'' in a PET study of working memory. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIMH,CBDB,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 1267 EP 1267 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62501153 ER PT J AU Ernst, M Zametkin, AJ Phillips, RL Cohen, RM AF Ernst, M Zametkin, AJ Phillips, RL Cohen, RM TI Influence of sex and age on brain glucose metabolism in control and ADHD adults. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. NIDA,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 1269 EP 1269 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62501155 ER PT J AU Castronovo, V vandenBrule, FA Jackers, P Clausse, N Liu, FT Gillet, C Sobel, ME AF Castronovo, V vandenBrule, FA Jackers, P Clausse, N Liu, FT Gillet, C Sobel, ME TI Decreased expression of galectin-3 is associated with progression of human breast cancer SO JOURNAL OF PATHOLOGY LA English DT Article DE breast cancer; galectin-3; expression; immunohistochemistry ID GALACTOSIDE-BINDING LECTIN; TUMOR INVASION; COLON-CARCINOMA; MESSENGER-RNA; LAMININ; CELLS; METASTASIS; PROTEINS AB Galectin-3, a member of the beta-galactoside-binding lectin family, is involved in several biological events including binding to the basement membrane glycoprotein laminin, Although the exact role of galectin-3 during the interactions between cells and laminin is not yet known, it has recently been observed that its expression is down-regulated at both the protein and the mRNA level in colon cancer tissues in correlation with progression of the disease, This study investigated the possibility that breast cancer cells might also exhibit decreased galectin-3 expression in association with their aggressiveness, The expression of galectin-3 was examined by immunoperoxidase staining, using a polyclonal antibody raised against recombinant galectin-3, in a collection of 98 human breast lesions including 12 fibroadenomas, 15 fibrocystic disease lesions, 22 in situ carcinomas, and 49 infiltrating ductal carcinomas, 19 of which had positive axillary lymph nodes, No;mal breast tissue adjacent to the lesions was present in 59 biopsies, Normal breast tissue expressed high levels (3+) of galectin-3. High expression (2+ to 3+) was also found in most benign lesions examined, The expression of galectin-3 was significantly decreased in hr situ carcinoma and this down-regulation was more pronounced in invasive ductal carcinoma, particularly when associated with infiltration of axillary lymph nodes, These data constitute the first observation that galectin-3 is down-regulated in breast cancer and suggest the decreased expression of this galactoside-binding lectin is associated with the acquisition of the invasive and metastatic phenotype. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. SCRIPPS CLIN & RES FDN,LA JOLLA,CA 92037. RP Castronovo, V (reprint author), UNIV LIEGE,METASTASIS RES LAB,TOUR PATHOL,B-35,B-4000 LIEGE,BELGIUM. NR 20 TC 159 Z9 166 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0022-3417 J9 J PATHOL JI J. Pathol. PD MAY PY 1996 VL 179 IS 1 BP 43 EP 48 DI 10.1002/(SICI)1096-9896(199605)179:1<43::AID-PATH541>3.0.CO;2-N PG 6 WC Oncology; Pathology SC Oncology; Pathology GA UN956 UT WOS:A1996UN95600009 PM 8691344 ER PT J AU Domanski, M Follmann, D Pizzo, P AF Domanski, M Follmann, D Pizzo, P TI Cardiomyopathy related to acquired immunodeficiency syndrome in children - Reply SO JOURNAL OF PEDIATRICS LA English DT Letter C1 NIAID, CLIN TRIALS SCI RES GRP, BETHESDA, MD 20892 USA. RP Domanski, M (reprint author), NHLBI, BETHESDA, MD 20892 USA. NR 0 TC 1 Z9 1 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 1996 VL 128 IS 5 BP 721 EP 721 DI 10.1016/S0022-3476(96)80153-3 PN 1 PG 1 WC Pediatrics SC Pediatrics GA UJ946 UT WOS:A1996UJ94600032 ER PT J AU Nishikawa, S Nagata, T Morisaki, I Oka, T Ishida, H AF Nishikawa, S Nagata, T Morisaki, I Oka, T Ishida, H TI Pathogenesis of drug-induced gingival overgrowth. A review of studies in the rat model SO JOURNAL OF PERIODONTOLOGY LA English DT Review DE gingival hyperplasia/etiology; cyclosporine adverse effects; nifedipine adverse effects; phenytoin adverse effects ID FIBROBLASTS INVITRO; CYCLOSPORIN-A; HYPERPLASIA; NIFEDIPINE; PHENYTOIN; DIPHENYLHYDANTOIN; APOPTOSIS; INFLAMMATION; ENLARGEMENT; MECHANISMS AB DRUG-INDUCED GINGIVAL OVERGROWTH is a side effect associated principally with 3 types of drugs: anticonvulsant (phenytoin), immunosuppressant (cyclosporine A), and various calcium channel blockers (nifedipine, verapamil, diltiazem). In this review, we describe the features of phenytoin-, cyclosporine A- and nifedipine-induced gingival overgrowth in rats and discuss factors influencing the onset and severity of these disorders. There are several features common to the gingival overgrowth induced by these drugs: 1) gingival overgrowth is more conspicuous in the buccal than in the lingual gingiva and less severe in the maxilla than in the mandible; 2) once the blood concentration of the drug reaches a certain level as a result of increasing the dose, the incidence of gingival overgrowth is 100% and its severity is dependent on the blood level, the most severe overgrowth being induced by cyclosporine A; 3) the duration of drug administration for maximal gingival overgrowth to develop is about 40 days; 4) the gingival overgrowth regresses spontaneously after discontinuing the drug; 5) accumulation of dental plaque is not essential for the onset of overgrowth, but plays a role in its severity; and 6) more severe overgrowth is induced in young than in old rats. Furthermore, male rats are more susceptible than females to nifedipine-induced gingival overgrowth. These results suggest that drug-induced gingival overgrowth in rats is dependent on the oral drug dose, blood drug level, age, and sex and that preexisting gingival inflammation is a factor relevant to its severity. Since these factors have also been suggested to be important determinants for human drug-induced gingival overgrowth, the rat model may prove valuable in the future for elucidating the molecular pathogenesis of the disorder. C1 OSAKA UNIV,FAC DENT,CLIN UNIT DENT HANDICAPPED,OSAKA,JAPAN. NIDDKD,MOL & CELLULAR BIOL LAB,NIH,BETHESDA,MD 20892. RP Nishikawa, S (reprint author), UNIV TOKUSHIMA,SCH DENT,DEPT PERIODONTOL & ENDODONTOL,3-18-15 KURAMOTO CHO,TOKUSHIMA 770,JAPAN. NR 94 TC 70 Z9 79 U1 0 U2 6 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD MAY PY 1996 VL 67 IS 5 BP 463 EP 471 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UM411 UT WOS:A1996UM41100001 PM 8724703 ER PT J AU Pearce, RE Rodrigues, AD Goldstein, JA Parkinson, A AF Pearce, RE Rodrigues, AD Goldstein, JA Parkinson, A TI Identification of the human P450 enzymes involved in lansoprazole metabolism SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID S-MEPHENYTOIN 4'-HYDROXYLATION; HUMAN-LIVER CYTOCHROME-P-450; OXIDATIVE DRUG-METABOLISM; GENETIC-POLYMORPHISM; POOR METABOLIZERS; OMEPRAZOLE; DIAZEPAM; PLASMA; HYDROXYLATION; PURIFICATION AB The aim of this study was to identify which human P450 enzymes are involved in the metabolism of lansoprazole. In the presence of NADPH and oxygen, human liver microsomes converted lansoprazole to lansoprazole sulfide, lansoprazole sulfone and 5-hydroxylansoprazole. Formation of lansoprazole sulfide occurred nonenzymatically. The formation of lansoprazole sulfone appeared to be catalyzed by a single, low-affinity enzyme (apparent K-m similar to 100 mu M). In contrast, lansoprazole 5-hydroxylation appeared to be catalyzed by two kinetically distinct enzymes (apparent K-m similar to 100 mu M and similar to 15 mu M). When human liver microsomes (n = 16) were incubated with 100 mu M lansoprazole, both the 5-hydroxylation and sulfoxidation of lansoprazole appeared to be catalyzed by CYP3A4/5 (based on correlation analyses). Antibodies against rat CYP3A enzymes inhibited the rate of both 5-hydroxylation (similar to 55%) and sulfoxidation (similar to 70%) and cDNA-expressed CYP3A4 catalyzed both the 5-hydroxylation and sulfoxidation of lansoprazole (apparent K-m similar to 100 mu M). However, at the pharmacologically relevant substrate concentration of 1 mu M, lansoprazole sulfoxidation was still highly correlated with CYP3A4/5 activity (r(2) = .905), but lansoprazole 5-hydroxylation appeared to be catalyzed by CYP2C19 (r(2) = .875) rather than CYP3A4/5 (r(2) = .113). Antibodies and chemical inhibitors of CYP2C enzymes preferentially inhibited the 5-hydroxylation of lansoprazole, whereas lansoprazole sulfoxidation was preferentially inhibited by antibodies and chemical inhibitors of CYP3A4/5. The cDNA expressed enzymes CYP2C8, CYP2C9 and CYP2C19 catalyzed varying rates of lansoprazole 5-hydroxylation at a substrate concentration of 50 mu M, but only CYPC19 catalyzed this reaction at 1 mu M. These results suggest that, at pharmacologically relevant concentrations, the 5-hydroxylation of lansoprazole is primarily catalyzed by CYP2C19, whereas the sulfoxidation of lansoprazole is primarily catalyzed by CYP3A4/5. It is possible that individuals lacking CYP2C19 will be poor metabolizers of lansoprazole. C1 UNIV KANSAS,MED CTR,DEPT PHARMACOL TOXICOL & THERAPEUT,CTR ENVIRONM & OCCUPAT HLTH,KANSAS CITY,KS 66160. ABBOTT LABS,DEPT DRUG METAB,ABBOTT PK,IL 60064. NIEHS,RES TRIANGLE PK,NC 27709. FU NIEHS NIH HHS [ES03765, ES07079]; NIGMS NIH HHS [GM37044] NR 51 TC 133 Z9 137 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 1996 VL 277 IS 2 BP 805 EP 816 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UJ953 UT WOS:A1996UJ95300032 PM 8627562 ER PT J AU Waalkes, MP Diwan, BA Rehm, S Ward, JM Moussa, M Cherian, MG Goyer, RA AF Waalkes, MP Diwan, BA Rehm, S Ward, JM Moussa, M Cherian, MG Goyer, RA TI Down-regulation of metallothionein expression in human and murine hepatocellular tumors: Association with the tumor-necrotizing and antineoplastic effects of cadmium in mice SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID B6C3F1 MOUSE-LIVER; IMMUNOHISTOCHEMICAL LOCALIZATION; CONFERS RESISTANCE; INDUCED TOLERANCE; SKIN TUMORS; TOXICITY; RAT; CISPLATIN; LUNG; CIS AB Previously, we found that oral cadmium (Cd) treatment either prevented or substantially reduced N-nitrosodiethylamine (NDEA)-induced tumor formation in B6C3F1 mouse liver or lung regardless of exposure interval and even when the Cd was given well after tumors were formed. Because Cd salts are powerful emetics, oral exposure would probably be impractical in humans. Thus, we studied suppression of NDEA-initiated tumors in male B6C3F1 mice by a single i.v. dose of Cd. NDEA (776 mu mol/kg i.p.) was given at time 0 followed by CdCl2 (16 mu mol/kg i.v.) 40 weeks later. This dose of Cd had no effect on body weights through the conclusion of the study at 52 weeks. The NDEA-induced increase in hepatic tumor incidence (19 tumor-bearing mice/22 mice at risk, 86%) over control (5/24, 21%) was remarkably reduced by Cd treatment (13/27, 48%, P less than or equal to .05). Multiplicity and size of liver tumors induced by NDEA (2.18 tumors/liver; 31.6 mm(3) mean volume) were also substantially reduced by the Cd exposure (0.96 tumors/liver; 17.1 mm(3) mean volume). NDEA-induced lung tumor incidence (22/22, 100%) and multiplicity (5.09 tumors/lung) were modestly, but significantly, reduced by Cd treatment (21/27, 78%; 3.89 tumors/lung). Clear evidence of tumor-specific cytotoxicity was observed as Cd treatment induced a necrotizing effect that was localized only within the hepatic tumors. Metallothionein (MT), an inducible metal-binding protein associated with tolerance to many metals including Cd, was not detected immunohistochemically in mouse liver tumors, even those undergoing Cd-induced necrosis, whereas the surrounding normal liver cells expressed high levels of MT after Cd exposure. Likewise, in human hepatocellular carcinomas MT was only poorly or erratically expressed relative to normal tissue. These results indicate that a single, nontoxic dose of Cd dramatically reduces liver tumor burden through tumor cell-specific necrosis due to a down-regulation of MT expression in hepatic tumors of murine origin and furthermore indicate that a similar down-regulation of MT occurs in human hepatocellular carcinomas. C1 NCI,VET TUMOR PATHOL SECT,OFF LAB ANIM SCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. UNIV WESTERN ONTARIO,DEPT PATHOL,LONDON,ON N6A 5C1,CANADA. RP Waalkes, MP (reprint author), NCI,INORGAN CARCINOGENESIS SECT,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. NR 45 TC 40 Z9 46 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 1996 VL 277 IS 2 BP 1026 EP 1033 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UJ953 UT WOS:A1996UJ95300057 PM 8627513 ER PT J AU Marples, D Knepper, MA Taylor, A Nielsen, S AF Marples, D Knepper, MA Taylor, A Nielsen, S TI Dynein is present in rat collecting duct principal cells, and colocalizes with vesicles containing aquaporin-2 (AQP2) water channels SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Meeting Abstract C1 UNIV AARHUS,DEPT CELL BIOL,DK-8200 AARHUS,DENMARK. NIH,BETHESDA,MD 20892. UNIV OXFORD,PHYSIOL LAB,OXFORD OX1 3PT,ENGLAND. NR 2 TC 0 Z9 0 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD MAY PY 1996 VL 493P BP P69 EP P70 PG 2 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA UX325 UT WOS:A1996UX32500085 ER PT J AU Nielsen, S Marples, D Knepper, MA AF Nielsen, S Marples, D Knepper, MA TI Aquaporin water channels in kidney: Expression and regulation SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Meeting Abstract ID COLLECTING DUCT; RAT-KIDNEY; VASOPRESSIN C1 AARHUS UNIV,DEPT CELL BIOL,AARHUS,DENMARK. NHLBI,KIDNEY & ELECTROLYTE LAB,NIH,BETHESDA,MD. NR 17 TC 0 Z9 0 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD MAY PY 1996 VL 493P BP S3 EP S4 PG 2 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA UX325 UT WOS:A1996UX32500156 ER PT J AU Smith, CP Shayakul, C Knepper, MA Hediger, MA AF Smith, CP Shayakul, C Knepper, MA Hediger, MA TI Molecular physiology of urea transport SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Meeting Abstract C1 UNIV MANCHESTER,SCH BIOL SCI,MOLEC PHYSIOL GRP,MANCHESTER,LANCS,ENGLAND. BRIGHAM & WOMENS HOSP,DIV RENAL,DEPT MED,BOSTON,MA. NHLBI,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD MAY PY 1996 VL 493P BP S2 EP S3 PG 2 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA UX325 UT WOS:A1996UX32500154 ER PT J AU Vogelgesang, SA Heyes, MP West, SG Salazar, AM Sfikakis, PP Lipnick, RN Klipple, GL Tsokos, GC AF Vogelgesang, SA Heyes, MP West, SG Salazar, AM Sfikakis, PP Lipnick, RN Klipple, GL Tsokos, GC TI Quinolinic acid in patients with systemic lupus erythematosus and neuropsychiatric manifestations SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE systemic lupus erythematosus; quinolinic acid; neuropsychiatric manifestations ID CENTRAL-NERVOUS-SYSTEM; KYNURENINE PATHWAY METABOLISM; CEREBROSPINAL-FLUID; L-TRYPTOPHAN; HUNTINGTONS-DISEASE; RAT-BRAIN; CLASSIFICATION; INCREASES; MECHANISM; CRITERIA AB Objective. To evaluate the relationship between quinolinic acid, a neuroactive metabolite of L-tryptophan, and neuropsychiatric manifestations of systemic lupus erythematosus (SLE). Methods. Forty specimens of cerebrospinal fluid (CSF) were obtained from 39 patients with SLE who were evaluated for 40 episodes of neuropsychiatric dysfunction. The diagnosis of the neuropsychiatric dysfunction was determined clinically. CSF and serum specimens were analyzed for levels of quinolinic acid without knowledge of the clinical diagnosis. Results. Neuropsychiatric dysfunction attributed to SLE (NPSLE) was confirmed in 30 patient-episodes (Group 1), whereas in the other 10 (Group 2) other etiologies were felt to explain their CNS dysfunction. The median levels of CSF quinolinic acid for Group 1 (232.5 nmol/l) were significantly higher than those for Group 2 (median 38.2 nmol/l) (p < 0.014). CSF and serum quinolinic acid levels correlated significantly (p < 0.003) but there was no correlation between CSF quinolinic acid and CSF protein concentrations or white blood cell counts. Conclusion. We conclude that elevated quinolinic acid levels in the CSF and serum may be associated with NPSLE and could possibly play a role in its pathogenesis. C1 WALTER REED ARMY MED CTR,RHEUMATOL SERV,WASHINGTON,DC 20307. FITZSIMONS ARMY MED CTR,RHEUMATOL SERV,AURORA,CO 80045. NIMH,ANALYT BIOCHEM SECT,CLIN SCI LAB,BETHESDA,MD 20892. WRAMC,DEPT CLIN INVEST,BETHESDA,MD. UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814. WRAMC,DEPT NEUROL,WASHINGTON,DC 20307. USUHS,DEPT NEUROL,WASHINGTON,DC. WRAMC,DEPT CLIN PHYSIOL,WASHINGTON,DC 20307. NR 30 TC 21 Z9 21 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAY PY 1996 VL 23 IS 5 BP 850 EP 855 PG 6 WC Rheumatology SC Rheumatology GA UJ948 UT WOS:A1996UJ94800012 PM 8724297 ER PT J AU Jacobsson, LTH Nagi, DK Pillemer, SR Knowler, WC Hanson, RL Pettitt, DJ Bennett, PH AF Jacobsson, LTH Nagi, DK Pillemer, SR Knowler, WC Hanson, RL Pettitt, DJ Bennett, PH TI Low prevalences of chronic widespread pain and shoulder disorders among the Pima Indians SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE shoulder; fibromyalgia; epidemiology; American Indians ID RHEUMATOID-ARTHRITIS; PRIMARY FIBROMYALGIA; RISK-FACTORS; DISABILITY; POPULATION; WORKERS AB Objective. To establish the prevalence of shoulder disease and chronic widespread pain in Pima Indians. Methods. Cross sectional analyses of data from 4230 subjects for shoulder disease and 105 subjects for chronic widespread pain participating in population surveys. Results. The prevalence of shoulder disease was 4.4% (95% CI, 3.8-5.1), age-sex adjusted to the 1980 US census population. This is lower than in a study of Caucasians [prevalence ratio (PR) = 0.29, 95% CI, 0.20-0.42 for men and PR = 0.55, 95% CI, 0.41-0.73 for women]. Shoulder disease was associated with non-insulin-dependent diabetes mellitus (PR = 1.67, 95% CI, 1.19-2.36). No chronic widespread pain was identified (95% CI, 0-3.5%). Conclusion. Prevalence of these pain syndromes in Pima Indians is lower than in predominantly Caucasian populations. These findings suggest that these populations have different pain perception or different patterns of risk factors for these disorders. C1 NIAMS,PHOENIX,AZ. NIAMS,BETHESDA,MD. NIDDK,DIABET & ARTHRITIS EPIDEMIOL SECT,PHOENIX,AZ. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 28 TC 22 Z9 22 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAY PY 1996 VL 23 IS 5 BP 907 EP 909 PG 3 WC Rheumatology SC Rheumatology GA UJ948 UT WOS:A1996UJ94800022 PM 8724307 ER PT J AU Miyaguchi, K Reese, TS AF Miyaguchi, K Reese, TS TI Direct visualization of a transmembrane channel associated with ribosomes SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article ID ENDOPLASMIC-RETICULUM MEMBRANE; PROTEIN TRANSLOCATION AB Examination of directly frozen rough endoplasmic reticulum (ER) of retinal pigment epithelial cells by freeze-fracture and freeze-substitution revealed distinct paired transmembrane proteins associated with membrane ribosomes. Ribosomal subunits on intact ER membrane are directly visualized for the first time, providing a global view of the structure of the ribosome and the corresponding structures on the ER membrane, The ribosomal intersubunit cleft appears to be continuous with a cleft between paired transmembrane proteins that extends into the lumen of the ER, This continuous cleft may be the path taken by nascent polypeptides. (C) 1996 Academic Press, Inc. C1 OSAKA UNIV,SCH MED,DEPT ANAT,SUITA,OSAKA 565,JAPAN. RP Miyaguchi, K (reprint author), NINCDS,NEUROBIOL LAB,NIH,BLDG 36,ROOM 2A-21,BETHESDA,MD 20892, USA. NR 28 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD MAY-JUN PY 1996 VL 116 IS 3 BP 413 EP 417 DI 10.1006/jsbi.1996.0058 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA UN556 UT WOS:A1996UN55600008 PM 8812999 ER PT J AU Denucci, DJ Dionne, RA Dubner, R AF Denucci, DJ Dionne, RA Dubner, R TI Identifying a neurobiologic basis for drug therapy in TMDs SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CHRONIC PAIN PATIENTS; DYSFUNCTION SYNDROME; DIABETIC NEUROPATHY; JOINT DYSFUNCTION; NONMALIGNANT PAIN; SPLINT THERAPY; OPIOID THERAPY; FACIAL-PAIN; AMITRIPTYLINE AB Emerging results from clinical and basic research indicate that persistent pain results in changes in the central nervous system. These changes may help explain chronic orofacial pain and lead to new therapies. The authors review data that support the use of tricyclic antidepressants for neurogenic or atypical pain, and benzodiazepines for musculoskeletal pain. Dentists must weigh the benefits of the chronic administration of a drug for the management of temporomandibular disorders against the equivocal scientific support for the use of many drug classes and the potential for serious toxicity with prolonged administration. C1 NIDR,NATL INST HLTH,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. UNIV MARYLAND,BALTIMORE COLL DENT SURG,DEPT ORAL & CRANIOFACIAL BIOL SCI,SCH MED,BALTIMORE,MD 21201. RP Denucci, DJ (reprint author), USA,WALTER REED ARMY MED CTR,DENT CORPS,BETHESDA,MD, USA. NR 80 TC 33 Z9 34 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD MAY PY 1996 VL 127 IS 5 BP 581 EP 593 PG 13 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UK210 UT WOS:A1996UK21000014 PM 8642138 ER PT J AU Slavkin, HC AF Slavkin, HC TI Meeting the challenges of craniofacial-oral-dental birth defects SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article RP Slavkin, HC (reprint author), NIDR,31 CTR DR,MSC 2290,BLDG 31,ROOM 2C39,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD MAY PY 1996 VL 127 IS 5 BP 681 EP 682 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UK210 UT WOS:A1996UK21000024 PM 8642148 ER PT J AU Yang, YM Wilbur, J AF Yang, YM Wilbur, J TI Using corpus statistics to remove redundant words in text categorization SO JOURNAL OF THE AMERICAN SOCIETY FOR INFORMATION SCIENCE LA English DT Article AB This article studies aggressive word removal in text categorization to reduce the noise in free texts and to enhance the computational efficiency of categorization. We use a novel stop word identification method to automatically generate domain specific stoplists which are much larger than a conventional domain-independent stoplist. In our tests with three categorization methods on text collections from different domains/applications, significant numbers of words were removed without sacrificing categorization effectiveness. In the test of the Expert Network method on CACM documents, for example, an 87% removal of unique words reduced the vocabulary of documents from 8,002 distinct words to 1,045 words, which resulted in a 63% time savings and a 74% memory savings in the computation of category ranking, with a 10% precision improvement on average over not using word removal. It is evident in this study that automated word removal based on corpus statistics has a practical and significant impact on the computational tractability of categorization methods in large databases. C1 NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. RP Yang, YM (reprint author), MAYO CLIN & MAYO FDN,SECT MED INFORM RESOURCES,ROCHESTER,MN 55905, USA. NR 28 TC 14 Z9 16 U1 1 U2 4 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0002-8231 J9 J AM SOC INFORM SCI JI J. Am. Soc. Inf. Sci. PD MAY PY 1996 VL 47 IS 5 BP 357 EP 369 PG 13 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA UE811 UT WOS:A1996UE81100003 ER PT J AU Humphrey, SM AF Humphrey, SM TI Legal informatics SO JOURNAL OF THE AMERICAN SOCIETY FOR INFORMATION SCIENCE LA English DT Letter RP Humphrey, SM (reprint author), NATL LIB MED,LISTER HILL NATL CTR BIOMED COMMUN,BETHESDA,MD 20894, USA. NR 2 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0002-8231 J9 J AM SOC INFORM SCI JI J. Am. Soc. Inf. Sci. PD MAY PY 1996 VL 47 IS 5 BP 407 EP 408 DI 10.1002/(SICI)1097-4571(199605)47:5<407::AID-ASI19>3.0.CO;2-X PG 2 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA UE811 UT WOS:A1996UE81100015 ER PT J AU Ziegler, RG Colavito, EA Hartge, P McAdams, MJ Schoenberg, JB Mason, TJ Fraumeni, JF AF Ziegler, RG Colavito, EA Hartge, P McAdams, MJ Schoenberg, JB Mason, TJ Fraumeni, JF TI Importance of alpha-carotene, beta-carotene, and other phytochemicals in the etiology of lung cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ANALYTIC DATA; NEW-JERSEY; WHITE MEN; VITAMIN-E; VEGETABLES; RISK; FRUITS; REDUCE; FOODS C1 NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. INFORMAT MANAGEMENT SERV INC,ROCKVILLE,MD. NEW JERSEY DEPT HLTH,SPECIAL EPIDEMIOL PROGRAM,TRENTON,NJ. NR 31 TC 131 Z9 134 U1 0 U2 5 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 1 PY 1996 VL 88 IS 9 BP 612 EP 615 DI 10.1093/jnci/88.9.612 PG 4 WC Oncology SC Oncology GA UG830 UT WOS:A1996UG83000015 PM 8609663 ER PT J AU Strup, SE Sindelar, WF Walther, MM AF Strup, SE Sindelar, WF Walther, MM TI The use of transureteroureterostomy in the management of complex ureteral problems SO JOURNAL OF UROLOGY LA English DT Article DE ureterostomy; ureteral neoplasms; ureteral diseases; ureteral stricture; urinary diversion ID EXPERIENCE AB Purpose: Transureteroureterostomy has primarily been performed for benign disease in children with reflux or undergoing undiversion, and in adults with lower ureteral injury, We report the use of transureteroureterostomy for other than these traditional indications, including malignant disease. Materials and Methods: Transureteroureterostomy was performed in 6 patients at the time of tumor resection to bypass large ureteral defects and in 4 as a secondary operation, usually associated with a ureteral leak after previous surgery. Results: Complications related to transureteroureterostomy included 1 ureteral stricture and 1 ureteral leak. Good renal function was maintained with a mean followup of 77.9 months. Conclusions: Our experience suggests that transureteroureterostomy can be useful for urinary diversion when a segment of lower ureter is involved with malignant disease. RP Strup, SE (reprint author), NCI,SURG BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 13 TC 11 Z9 11 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 1996 VL 155 IS 5 BP 1572 EP 1574 DI 10.1016/S0022-5347(01)66129-9 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA UF008 UT WOS:A1996UF00800007 PM 8627825 ER PT J AU Wu, SC Spouge, JL Merges, MJ Conley, SR Nara, PL AF Wu, SC Spouge, JL Merges, MJ Conley, SR Nara, PL TI A cytopathic infectivity assay of human immunodeficiency virus type 1 in human primary macrophages SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE HIV-1; infectivity assay; primary macrophage; cytopathology ID MONOCYTE-MACROPHAGES; HIV-1; QUANTIFICATION AB In addiction to CD4+ T lymphocytes, cells of monocyte/macrophage lineage are a major target for human immunodeficiency virus type 1 (HIV-1) infection. In vitro studies of HIV-1 infection in human monocyte-derived macrophages can be undertaken by a reproducible cell-based assay. A macrophage-based infectivity assay was developed based on the semi-quantitative scoring of HIV-1 induced cytopathology in monolayer macrophage cultures. The assay exhibited dilution-dependent linearity with all three primary macrophage-tropic isolates tested. The end-point infectivity titers determined by this assay correlated with the results obtained by detecting viral p24 antigen in the culture supernatant. The applications of the assay in both neutralization and anti-viral protocols yielded identical results with the more time-consuming and costly p24 formats. Since the assay offers a simple and low-cost method of measuring HIV-1 infectivity in human primary macrophages, it can be used quite easily for large-scale screening or evaluation of candidate vaccines and anti-viral agents. C1 NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. NCI,FREDERICK CANC RES & DEV CTR,VIRUS BIOL SECT,LAB TUMOR CELL BIOL,FREDERICK,MD 21702. SAIC FREDERICK,FREDERICK,MD 21702. NR 30 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD MAY PY 1996 VL 59 IS 1-2 BP 45 EP 55 DI 10.1016/0166-0934(96)02005-8 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA UT452 UT WOS:A1996UT45200005 PM 8793829 ER PT J AU Hughes, SH Hostomsky, Z LeGrice, SFJ Lent, K Arnold, E AF Hughes, SH Hostomsky, Z LeGrice, SFJ Lent, K Arnold, E TI What is the orientation of DNA polymerases on their templates? SO JOURNAL OF VIROLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 REVERSE-TRANSCRIPTASE; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; BETA C1 AGOURON PHARMACEUT INC,SAN DIEGO,CA 92121. CASE WESTERN RESERVE UNIV,SCH MED,DIV INFECT DIS,CLEVELAND,OH 44106. RUTGERS STATE UNIV,DEPT CHEM,CTR ADV BIOTECHNOL & MED,PISCATAWAY,NJ 08854. RP Hughes, SH (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,POB B,FREDERICK,MD 21702, USA. FU NIAID NIH HHS [AI131147, AI33380]; NIGMS NIH HHS [GM52263] NR 36 TC 17 Z9 17 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1996 VL 70 IS 5 BP 2679 EP 2683 PG 5 WC Virology SC Virology GA UF247 UT WOS:A1996UF24700001 PM 8627740 ER PT J AU Mikovits, JA Hoffman, PM Rethwilm, A Ruscetti, FW AF Mikovits, JA Hoffman, PM Rethwilm, A Ruscetti, FW TI In vitro infection of primary and retrovirus-infected human leukocytes by human foamy virus SO JOURNAL OF VIROLOGY LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; LONG TERMINAL REPEAT; HUMAN SPUMARETROVIRUS; MICROGLIAL CELLS; TRANSGENIC MICE; GENE-EXPRESSION; HUMAN-MONOCYTES; READING FRAMES; HTLV-III/LAV; DNA AB The infectivity of human foamy virus (HFV) was examined in primary and cultured human leukocytes; Cell-free infectious viral stocks of HFV were prepared from the human kidney cell line 293 transfected with an infectious molecular clone of HFV. HFV productively infects a variety of human myeloid and lymphoid cell lines. In addition, primary cell cultures enriched for human CD4(+), monocytes and brain-derived microglial cells, were readily infected by HFV. Interestingly, while infected primary CD4(+) lymphocytes and microglial cells showed marked cytopathology characteristic of foamy virus, HFV-infected monocyte-derived macrophages failed to show any cytopathology. In addition, marked cytotoxicity due to HFV infection was seen in both human T-cell leukemia virus type 1- and human immunodeficiency virus type 1-infected T-cell lines and in human immunodeficiency virus type I-infected monocytoid cell lines. Thus, HFV infection produces differential cytopathology in a wide host range of primary human leukocytes and hematopoietic cell lines. C1 SAIC,BIOL CARCINOGENESIS DEV PROGRAM,FREDERICK,MD. UNIV MARYLAND,VET ADM MED CTR,BALTIMORE,MD 21201. UNIV MARYLAND,DEPT NEUROL,BALTIMORE,MD 21201. UNIV WURZBURG,INST VIROL & IMMUNOBIOL,D-97078 WURZBURG,GERMANY. RP Mikovits, JA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,LAB LEUKOCYTE BIOL,POB B,BLDG 567,RM 253,FREDERICK,MD 21702, USA. NR 50 TC 28 Z9 28 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1996 VL 70 IS 5 BP 2774 EP 2780 PG 7 WC Virology SC Virology GA UF247 UT WOS:A1996UF24700012 PM 8627751 ER PT J AU Wolffe, EJ Moore, DM Peters, PJ Moss, B AF Wolffe, EJ Moore, DM Peters, PJ Moss, B TI Vaccinia virus A17L open reading frame encodes an essential component of nascent viral membranes that is required to initiate morphogenesis SO JOURNAL OF VIROLOGY LA English DT Article ID COLI LAC REPRESSOR; EXTRACELLULAR VIRUS; ESCHERICHIA-COLI; ENVELOPE PROTEIN; NUCLEOTIDE-SEQUENCE; PROGENY VACCINIA; GENE; EXPRESSION; GLYCOPROTEIN; RESISTANCE AB We generated an antiserum to the predicted C-terminal peptide of the A17L open reading frame (ORF), which encodes a 23-kDa polypeptide with hydrophobic regions characteristic of membrane proteins. Immuno-electron microscopy of infected cells indicated that the A17L protein is intimately associated with the earliest characteristic viral membranes, even those formed in the presence of the drug rifampin. To study the role of the A17L protein in morphogenesis, we constructed recombinant vaccinia viruses in which the endogenous A17L ORF was deleted and a copy of the ORF under the control of the bacteriophage T7 RNA polymerase and the Escherichia call lac repressor was inserted into an alternative site in the vaccinia virus genome. Growth of these recombinant viruses was entirely dependent on the induction of A17L expression by isopropyl-beta-D-thiogalactopyranoside. Electron microscopic examination of cells infected in the absence of inducer revealed the accumulation of large, well-demarcated electron-dense aggregates but no characteristic membrane-associated viral structures. Viral late protein synthesis occurred under these conditions, although the maturational proteolytic processing of structural proteins was inhibited. We conclude that the product of the A17L gene is an essential component of the immature viral membrane and has an early function in viral morphogenesis. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. UNIV UTRECHT,SCH MED,CELL BIOL LAB,UTRECHT,NETHERLANDS. USDA ARS,PLUM ISL ANIM DIS CTR,ASF RES,GREENPORT,NY 11944. NR 67 TC 106 Z9 106 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1996 VL 70 IS 5 BP 2797 EP 2808 PG 12 WC Virology SC Virology GA UF247 UT WOS:A1996UF24700015 PM 8627754 ER PT J AU Lapham, C Golding, B Inman, J Blackburn, R Manischewitz, J Highet, P Golding, H AF Lapham, C Golding, B Inman, J Blackburn, R Manischewitz, J Highet, P Golding, H TI Brucella abortus conjugated with a peptide derived from the V3 loop of human immunodeficiency virus (HIV) type 1 induces HIV-Specific cytotoxic T-cell responses in normal and in CD4(+) cell-depleted BALB/c mice SO JOURNAL OF VIROLOGY LA English DT Article ID GENE-EXPRESSION; LYMPHOCYTES-T; MOLECULES; PROTEINS; ANTIGENS; PRIMES; GAMMA AB We have previously shown that immunization of mice with human immunodeficiency virus (HIV)-derived proteins or peptides conjugated to inactivated Brucella abortus induces the secretion of virus-neutralizing antibodies, predominantly of the immunoglobulin G2a (IgG2a) isotype, In addition, B, abortus activates human CD4(+) and CD8(+) cells to secrete gamma interferon. Since these are both characteristics of a Th1-type immune response, which is associated with the development of cell-mediated immunity, it was important to determine if B. abortus conjugates would also act as a carrier to induce a cytotoxic T-lymphocyte (CTL) response, To test this hypothesis, we conjugated an 18-amino-acid peptide from the V3 loop of the MN strain of HIV-1 gp120 that contains both B- and cytotoxic T-cell epitopes to B, abortus (B. abortus-MN 18-mer), A 10-amino-acid fragment of this peptide has been shown to be the minimal CTE determinant presented by murine H-2D(d), It was found that two in vivo immunizations with 10(8) organisms of B. abortus-MN 18-mer followed by in vitro stimulation with peptide induced a virus-specific CTL response, Conjugation to B. abortus was required for in vive priming, since there was no induction of memory CTLs when B. abortus was only mixed with peptide, Targets pulsed with peptide as well as those infected with a vaccinia virus encoding HIV gp160 were killed, demonstrating recognition of naturally processed envelope, Also, major histocompatibility complex-incompatible L cells which were infected with vaccinia viruses that encoded H-2D(d) but not H-2k(d), and pulsed with peptide were lysed, This demonstrated the appropriate major histocompatibility complex class I restriction, Treatment of the mice with anti-L3T4 prior to immunization caused a severe depletion of CD4(+) lymphocytes, yet it did not decrease the CTL priming, Thus, inactivated B. abortus can induce non-CD4(+) cells to produce the cytokines required for CTL induction, We conclude that B, abortus stimulates a cellular as well as a humoral immune response, even in the relative absence of CD4(+) helper cells, It may be a particularly useful vaccine carrier in HIV-1-infected individuals or others with impaired CD4(+) T-cell function. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,LAB PLASMA DERIVAT,BETHESDA,MD 20892. NIAID,BETHESDA,MD 20892. RP Lapham, C (reprint author), US FDA,CTR BIOL EVALUAT & RES,LAB RETROVIRUS RES,DIV VIRAL PROD,BLDG 29B,RM 3G21,HFM 454,BETHESDA,MD 20892, USA. NR 37 TC 26 Z9 28 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1996 VL 70 IS 5 BP 3084 EP 3092 PG 9 WC Virology SC Virology GA UF247 UT WOS:A1996UF24700048 PM 8627787 ER PT J AU Oleksiewicz, MB Costello, F Huhtanen, M Wolfinbarger, JB Alexandersen, S Bloom, ME AF Oleksiewicz, MB Costello, F Huhtanen, M Wolfinbarger, JB Alexandersen, S Bloom, ME TI Subcellular localization of Aleutian mink disease parvovirus proteins and DNA during permissive infection of Crandell feline kidney cells SO JOURNAL OF VIROLOGY LA English DT Article ID MINUTE VIRUS; NUCLEOTIDE-SEQUENCE; VIRAL REPLICATION; BINDING PROTEIN; MURINE CELLS; ADULT MINK; RAT-CELLS; MICE; EXPRESSION; IDENTIFICATION AB Confocal microscopy allowed us to localize viral nonstructural (NS) and capsid (VP) proteins and DNA simultaneously in cells permissively infected with Aleutian mink disease parvovirus (ADV). Early after infection, NS proteins colocalized with viral DNA to form intranuclear inclusions, whereas VP proteins formed hollow intranuclear shells around the inclusions. Later, nuclei had irregular outlines and were virtually free of ADV products. In these cells, inclusions of viral DNA with or without associated NS protein were embedded in cytoplasmic VP protein. These findings implied that ADV replication within an infected cell is regulated spatially as well as temporally. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. DANISH VET INST VIRUS RES,DK-4771 KALVEHAVE,DENMARK. OI Alexandersen, Soren/0000-0002-5039-3178 NR 44 TC 17 Z9 17 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1996 VL 70 IS 5 BP 3242 EP 3247 PG 6 WC Virology SC Virology GA UF247 UT WOS:A1996UF24700066 PM 8627805 ER PT J AU Feigenbaum, L Fujita, K Collins, FS Jay, G AF Feigenbaum, L Fujita, K Collins, FS Jay, G TI Repression of the NF1 gene by Tax may explain the development of neurofibromas in human T-lymphotropic virus type 1 transgenic mice SO JOURNAL OF VIROLOGY LA English DT Article ID TROPICAL SPASTIC PARAPARESIS; HTLV-I; MOUSE MODEL; PROTEIN PRODUCT; CELL LYMPHOMA; ANTIBODIES; LEUKEMIA; IDENTIFICATION; POLYMYOSITIS; EXPRESSION AB In familial neurofibromatosis type 1 (NF1), individuals with a germ line-transmitted NF1 mutation develop multiple neurofibromas. To explain the observation that transgenic mice expressing the human T-lymphotropic virus type 1 (HTLV-1) tax gene under the control of the viral regulatory element also develop multiple neurofibromas, we demonstrate that the Tax trans-regulator can functionally repress NF1 gene expression through a cis-acting element located immediately upstream of its transcriptional start site, thereby allowing the development of benign neurofibromas without the need for direct mutations in NF1. We propose that such a mechanism would suffice to epigenetically alter NF1 gene expression. The fact that transgenic animals have localized rather than diffuse neurofibroma formation, however, suggests that additional genetic or epigenetic events may be required for neurofibroma formation. C1 AMER RED CROSS,JEROME H HOLLAND LAB,DEPT VIROL,ROCKVILLE,MD 20855. NATL CTR HUMAN GENOME RES,NIH,BETHESDA,MD 20892. RI Jay, Gregory/C-6346-2013 FU NCI NIH HHS [CA51779] NR 50 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1996 VL 70 IS 5 BP 3280 EP 3285 PG 6 WC Virology SC Virology GA UF247 UT WOS:A1996UF24700072 PM 8627811 ER PT J AU Roden, RBS Hubbert, NL Kirnbauer, R Christensen, ND Lowy, DR Schiller, JT AF Roden, RBS Hubbert, NL Kirnbauer, R Christensen, ND Lowy, DR Schiller, JT TI Assessment of the serological relatedness of genital human papillomaviruses by hemagglutination inhibition SO JOURNAL OF VIROLOGY LA English DT Article ID VIRUS-LIKE PARTICLES; ANTIBODY-MEDIATED NEUTRALIZATION; L1 PROTEIN; EXPRESSION; SEQUENCE; TYPE-11; INVIVO AB To assess the potential for cross-protection among genital human papillomavirus (HPV) types in virus-like particle (VLP)-based vaccinations, inhibition of HPV VLP-mediated hemagglutination by rabbit antisera raised against HPV type 6b (HPV-6b), HPV-11, HPV-16, HPV-18, HPV-31, HPV-33, and HPV-45 was analyzed. Only highly homologous types (HPV-6b and HPV-11, and HPV-18 and HPV-45) exhibited detectable serological cross-reaction for the class of antibodies that inhibit virion-to-cell surface binding. However, analysis of neutralizing monoclonal antibodies to several animal and human papillomaviruses indicated that over half of these antibodies do not prevent cell surface binding, but these latter antibodies do not appear to be more cross-reactive in enzyme-linked immunosorbent assays than those that mediate inhibition of hemagglutination. The data strongly suggest that while there may be limited cross-protection between highly (>85% L1 amino acid identity) homologous types, protection by HPV VLP-based vaccines will be predominantly type specific. C1 NCI,NIH,CELLULAR ONCOL LAB,BETHESDA,MD 20892. UNIV VIENNA,SCH MED,DEPT DERMATOL,DIV IMMUNOL ALLERGY & INFECT DIS,A-1090 VIENNA,AUSTRIA. MILTON S HERSHEY MED CTR,DEPT PATHOL,HERSHEY,PA 17033. NR 32 TC 130 Z9 137 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1996 VL 70 IS 5 BP 3298 EP 3301 PG 4 WC Virology SC Virology GA UF247 UT WOS:A1996UF24700075 PM 8627814 ER PT J AU Ferrucci, L Guralnik, JM Simonsick, E Salive, ME Corti, C Langlois, J AF Ferrucci, L Guralnik, JM Simonsick, E Salive, ME Corti, C Langlois, J TI Progressive versus catastrophic disability: A longitudinal view of the disablement process SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID PHYSICAL-DISABILITY; OLDER PERSONS; HEALTH-CARE; MORTALITY; POPULATION; LIFE; MORBIDITY; COMMUNITY; AMERICANS; ADULTS AB Background. There is little epidemiologic data on the development of disability over time in older persons. This study uses prospective data from cohorts followed annually for 6 to 7 years to identify persons who developed severe disability and to characterize the: time course of their disabling process and subsequent mortality. Methods. incidence rates of severe disability. defined as need for help in three or more activities of daily living (ADLs), were estimated for 6,640 persons who had not reported severe disability Lit baseline and at the first four annual follow-up visits. Among persons developing severe disability, those who reported no need for help in ADLs in previous interviews were defined as cases of catastrophic disability. and those who had previously reported some disability in ADLs were defined as cases of progressive disability. Results. Overall, 212 subjects developed progressive and 227 developed catastrophic disability. The rates of progressive disability and catastrophic disability were 11.3 and 12.1 cases per 1,000 person-years, respectively. For both types of disability. incidence rates increased exponentially with age, but the Increase was steeper for progressive disability. At ages 70-74, less than 25% of severe disability was progressive, while over age 85 progressive disability represented more than half of severe disability. Incidence rates of total and both types of severe disability were similar in men and women. Mortality after severe disability onset was extremely high. Survival time was unrelated to ate at disability onset and type of disability but was significantly longer in women than in men (median 3.44 vs 2.12 years: p < .0001). Conclusion. Tracking the development of disability provides new and important insights into the disability experience in older men and women that are potentially relevant in planning preventive, intervention. and long-term care strategies. C1 INRCA FLORENCE,I FRATICINI NATL RES INST,DEPT GERIATR,FLORENCE,ITALY. RP Ferrucci, L (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,7201 WISCONSIN AVE,GATEWAY BLDG,SUITE 3C-309,BETHESDA,MD 20892, USA. NR 41 TC 136 Z9 137 U1 2 U2 12 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 1996 VL 51 IS 3 BP M123 EP M130 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA VN555 UT WOS:A1996VN55500013 PM 8630705 ER PT J AU Iehara, N Takeoka, H Tsuji, H Imabayashi, T Foster, DN Strauch, AR Yamada, Y Kita, T Doi, T AF Iehara, N Takeoka, H Tsuji, H Imabayashi, T Foster, DN Strauch, AR Yamada, Y Kita, T Doi, T TI Differentiation of smooth muscle phenotypes in mouse mesangial cells SO KIDNEY INTERNATIONAL LA English DT Article ID DNA METHYLATION; EXTRACELLULAR-MATRIX; COLLAGEN GENE; CHLORAMPHENICOL ACETYLTRANSFERASE; TRANSCRIPTIONAL ACTIVATION; REGULATORY ELEMENTS; GLOMERULAR CELLS; GROWTH-HORMONE; MESSENGER-RNA; 1ST INTRON AB Smooth muscle alpha-actin (SMA) mRNA, a marker of vascular smooth muscle cells, was identified in the normal glomerular mesangium both in vivo and in vitro. Several populations of mesangial cells were studied to determine if SMA and basement membrane collagen were regulated together. The levels of SMA expression, which could be linked to the stage of differentiation, were different for the differing cell populations. One cell population had high SMA and type IV collagen levels at its early passages. The others expressed both interstitial and basement membrane collagens. The first population developed these phenotypic features at later passages. The levels of SMA and alpha 1(IV) collagen expression were regulated together in concert, whereas the alpha 2(I) collagen levels were expressed inversely to SMA and alpha 1(IV) collagen. Both SMA and type IV collagen were controlled by the methylation states of the cis-regulators; however, type I collagen was mainly regulated by the trans-acting regulators. Treatment with 5-azacytidine converted the cells of a fibroblast-phenotype to a smooth muscle cell-like phenotype. These cell lines may be useful for studying the differentiation process in vitro. C1 KYOTO UNIV,DIV ARTIFICIAL KIDNEYS,FAC MED,KYOTO,JAPAN. KYOTO UNIV,DIV MOL MED ADULT & GERIATR DIS,FAC MED,DEPT CLIN BIOREGULATORY SCI,KYOTO,JAPAN. NIDR,DEV BIOL LAB,NIH,BETHESDA,MD 20892. UNIV MINNESOTA,COLL VET MED,DEPT ANIM SCI,ST PAUL,MN 55108. OHIO STATE UNIV,COLL MED,DEPT CELL BIOL,COLUMBUS,OH 43210. OHIO STATE UNIV,COLL MED,DEPT ANAT & NEUROBIOL,COLUMBUS,OH 43210. NR 50 TC 12 Z9 12 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 1996 VL 49 IS 5 BP 1330 EP 1341 DI 10.1038/ki.1996.189 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA UF620 UT WOS:A1996UF62000019 PM 8731098 ER PT J AU Snow, JB AF Snow, JB TI Evolution of research in otolaryngology - Head and neck surgery over the past century SO LARYNGOSCOPE LA English DT Article RP Snow, JB (reprint author), NIDOCD,BLDG 31,ROOM 3C02,BETHESDA,MD 20892, USA. NR 9 TC 2 Z9 2 U1 0 U2 0 PU LARYNGOSCOPE CO PI ST LOUIS PA 10 S BROADWAY 14TH FLOOR, ST LOUIS, MO 63102-1741 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAY PY 1996 VL 106 IS 5 BP 529 EP 531 DI 10.1097/00005537-199605000-00002 PN 1 PG 3 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA UT403 UT WOS:A1996UT40300002 PM 8628076 ER PT J AU Clark, HM Yano, T Sander, C Jaffe, ES Raffeld, M AF Clark, HM Yano, T Sander, C Jaffe, ES Raffeld, M TI Mutation of the ras genes is a rare genetic event in the histologic transformation of follicular lymphoma SO LEUKEMIA LA English DT Article DE ras oncogenes; follicular lymphomas; transformation; molecular pathogenesis ID NON-HODGKINS-LYMPHOMA; ACUTE MYELOID-LEUKEMIA; N-RAS; MULTIPLE-MYELOMA; POINT MUTATIONS; POOR-PROGNOSIS; PROGRESSION; P53; MALIGNANCIES; PREVALENCE AB The role of ras gene mutations in the progression of follicular lymphoma has been ascertained by SSCP-PCR and sequencing. A total of 40 transformed lymphomas were studied, 16 of which had a matched preceding low-grade biopsy. Only one transformed lymphoma was found to have a missense mutation at codon 12 of N-ras, resulting in an amino acid change of glycine to serine. We conclude that mutation within the ras gene family is a rare event in the transformation of follicular lymphoma. C1 NCI,PATHOL LAB,HEMATOPATHOL SECT,NIH,BETHESDA,MD 20892. NR 32 TC 10 Z9 10 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 1996 VL 10 IS 5 BP 844 EP 847 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA UP256 UT WOS:A1996UP25600015 PM 8656681 ER PT J AU Liu, GY vanGelderen, P Duyn, J Moonen, CTW AF Liu, GY vanGelderen, P Duyn, J Moonen, CTW TI Single-shot diffusion MRI of human brain on a conventional clinical instrument SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE diffusion; brain; single-shot MRI; gradient and spin echo (GRASE); Car-Purcell-Meiboom-Gill (CPMG) ID GRASE GRADIENT-ECHO; CEREBRAL-ISCHEMIA; SELF-DIFFUSION; IMAGING TECHNIQUE; COEFFICIENT; STROKE; ERRORS; WATER; RATS AB A single-shot diffusion MRI technique on a standard clinical 1.5T scanner is presented. The method incorporates the following elements: (a) an inversion RF pulse followed by a delay of 1.3 s to null cerebral spinal fluid (CSF) signal, (b) a stimulated echo sequence (TE = 56 ms, TM = 100 ms) to obtain strong diffusion weighting, (c) a single-shot gradient- and spin-echo (GRASE) sequence for imaging with a modified k-space trajectory and Carr-Purcell Meiboom-Gill (CPMG)-phase cycle. The trace of the diffusion coefficient obtained with this approach is in good agreement with values reported for animal brain, and for recent human studies. It is demonstrated that single-shot diffusion imaging of human brain is feasible on an unmodified standard instrument without high-gradient slew rate or extreme field homogeneity. C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,INVIVO NMR RES CTR,BETHESDA,MD 20892. NIH,LAB DIAGNOST RADIOL RES,BETHESDA,MD 20892. RI Duyn, Jozef/F-2483-2010; Moonen, Chrit/K-4434-2016 OI Moonen, Chrit/0000-0001-5593-3121 NR 37 TC 37 Z9 39 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD MAY PY 1996 VL 35 IS 5 BP 671 EP 677 DI 10.1002/mrm.1910350508 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UJ175 UT WOS:A1996UJ17500007 PM 8722818 ER PT J AU Duewell, S Kasserra, CE Jezzard, P Balaban, RS AF Duewell, S Kasserra, CE Jezzard, P Balaban, RS TI Evaluation of methemoglobin as an autologous intravascular MRI contrast agent SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE paramagnetic contrast agent; methemoglobin; magnetic resonance imaging ID GD-DTPA AB Methemoglobin (MetHb) was evaluated as an intravascular paramagnetic contrast agent. Methemoglobin formation was induced by 4-dimethylaminophenol (4-DMAP), causing a reduction in blood T-2* in vitro. The 4-DMAP generated metHb with a time constant of 62 s. A 4-DMAP bolus did not decrease measurably the signal intensity in the in vivo rabbit kidney in the first pass. At steady state, a MetHb concentration of 24.8 +/- 2.3% resulted in a signal decrease of 9.2 +/- 2.6% in the kidney. Methemoglobin is an effective vascular T-2* relaxation agent, but the formation of MetHb by 4-DMAP is too slow for first-pass imaging. A more effective conversion agent resulting in a bolus of at least 25% MetHb within 5 s would result in a detectable first-pass signal and a viable contrast technique. C1 NHLBI,CARDIAC ENERGET LAB,NIH,BETHESDA,MD 20892. RI Balaban, Robert/A-7459-2009; OI Balaban, Robert/0000-0003-4086-0948; Jezzard, Peter/0000-0001-7912-2251 NR 13 TC 5 Z9 5 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD MAY PY 1996 VL 35 IS 5 BP 787 EP 789 DI 10.1002/mrm.1910350521 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UJ175 UT WOS:A1996UJ17500020 PM 8722831 ER PT J AU Wu, C Xu, W Kozak, CA Desnick, RJ AF Wu, C Xu, W Kozak, CA Desnick, RJ TI Mouse uroporphyrinogen decarboxylase: cDNA cloning, expression, and mapping SO MAMMALIAN GENOME LA English DT Article ID PORPHYRIA-CUTANEA-TARDA; HEPATOERYTHROPOIETIC-PORPHYRIA; NUCLEOTIDE-SEQUENCE; HUMAN-ERYTHROCYTES; MOLECULAR-CLONING; MUTATION; GENE; IDENTIFICATION; CHROMOSOME-1; ASSIGNMENT AB Uroporphyrinogen decarboxylase (URO-decarboxylase; EC 4.1.1.37), the heme biosynthetic enzyme responsible for the conversion of uroporphyrinogen III to coproporphyrinogen III, is the enzymatic defect in porphyria cutanea tarda, the most common porphyria. The mouse URO-decarboxylase cDNA was isolated from a mouse adult liver cDNA library. The longest clone of 1.5 kb, designated pmUROD-1, had 5' and 3' untranslated sequences of 281 and 97 bp, respectively, and an open reading frame of 1104 bp encoding a 367-amino acid polypeptide with a predicted molecular mass of 40,595 Da. The mouse and human coding sequences had 87.8% and 90.0% nucleotide and amino acid identity, respectively. The authenticity of the mouse cDNA was established by expression of the active enzyme in Escherichia coli. In addition, the analysis of two sets of multilocus genetic crosses localized the mouse gene, Urod, on Chromosome (Chr) 4, consistent with the map location of the human gene to a position of conserved synteny on Chr 1. The availability of the mouse URO-decarboxylase should facilitate studies of the structure and organization of the mouse genomic sequence and the development of a mouse model of this inherited porphyria. C1 CUNY MT SINAI SCH MED,DEPT HUMAN GENET,NEW YORK,NY 10029. NIAID,NATL INST HLTH,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. FU NCRR NIH HHS [5 M01 RR00071]; NICHD NIH HHS [5 P30 HD28822]; NIDDK NIH HHS [5 R01 DK26824] NR 40 TC 6 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD MAY PY 1996 VL 7 IS 5 BP 349 EP 352 DI 10.1007/s003359900101 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA UM129 UT WOS:A1996UM12900005 PM 8661721 ER PT J AU Huppi, K Siwarski, D Mock, BA Dosik, J Hamel, PA AF Huppi, K Siwarski, D Mock, BA Dosik, J Hamel, PA TI Molecular cloning, chromosomal mapping, and expression of the mouse p107 gene SO MAMMALIAN GENOME LA English DT Article ID RETINOBLASTOMA PROTEIN; CYCLIN-A; C-MYC; MUTATIONS; LYMPHOMA; FAMILY AB Progression through the G1 phase of the cell cycle is regulated, in part, by the pRB-family proteins, pRB and p107. The basis for this regulation is due to a network of interactions between the pRB-family proteins, pRB, p107, and p130; the E2F-family of transcription factors; and cyclins D, E, and A. One of the pRB-family proteins, p107, has also been found to bind to the transactivation domain of the c-Myc proto-oncogene. This region in c-Myc is frequently mutated in tumors such as Burkitt's lymphoma, HIV-associated lymphoma, and multiple myeloma. The binding of p107 and regulation of c-Myc may conceivably be disrupted not only by mutations in c-Myc, but possibly by mutations in p107. In order to determine if mutations in p107 are indeed present in mouse B-cell tumors which exhibit a lower frequency of c-Myc mutation, we have cloned the mouse p107 cDNA and compared this sequence with its human counterpart. We find that the extreme N-terminal and C-terminal regions are the most conserved between human and mouse p107 sequences. Chromosomal positioning of the locus for p107 (designated Rbl1) as well as E2f1 to the distal end of mouse Chromosome (Chr) 2 also suggests a close but unlinked genetic relationship between these cell cycle regulatory transcription factors. C1 UNIV TORONTO,DEPT MOLEC & CELLULAR PATHOL,TORONTO,ON M5S 1A8,CANADA. RP Huppi, K (reprint author), NATL CANC INST,NATL INST HLTH,GENET LAB,MOLEC GENET SECT,BLDG 37,ROOM 2B-21,BETHESDA,MD 20892, USA. NR 26 TC 6 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD MAY PY 1996 VL 7 IS 5 BP 353 EP 355 DI 10.1007/s003359900102 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA UM129 UT WOS:A1996UM12900006 PM 8661722 ER PT J AU Liao, X Zhou, R Gilbert, DJ Copeland, NG Jenkins, NA AF Liao, X Zhou, R Gilbert, DJ Copeland, NG Jenkins, NA TI Receptor tyrosine kinase gene Tyro3 maps to mouse chromosome 2, closely linked to Ltk SO MAMMALIAN GENOME LA English DT Article ID LINKAGE MAP C1 NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RUTGERS STATE UNIV,COLL PHARM,CANC RES LAB,PISCATAWAY,NJ 08855. NR 8 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD MAY PY 1996 VL 7 IS 5 BP 395 EP 396 DI 10.1007/s003359900116 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA UM129 UT WOS:A1996UM12900022 PM 8661736 ER PT J AU Sherman, CD Portier, CJ AF Sherman, CD Portier, CJ TI Stochastic simulation of a multistage model of carcinogenesis SO MATHEMATICAL BIOSCIENCES LA English DT Article ID CANCER AB Stochastic mathematical models of carcinogenesis have been used to quantify cancer risks for about 40 years. As more detailed data of the cancer process are obtained, mathematical models try to incorporate this information and as a result become more complex and sometimes analytically and numerically intractable. Simulation studies have become an important tool for examining the operating characteristics of the models of interest. The many quantities one can examine using this tool include bias in parameter estimates, adequacy of approximation methods, and the appropriateness of large sample generalizations to small studies. This manuscript describes a general method of stochastic simulation that may be carried out for arbitrarily complicated stochastic models of carcinogenesis. RP Sherman, CD (reprint author), NIEHS,LAB QUANTITAT & COMPUTAT BIOL,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 16 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 SN 0025-5564 J9 MATH BIOSCI JI Math. Biosci. PD MAY PY 1996 VL 134 IS 1 BP 35 EP 50 DI 10.1016/0025-5564(95)00105-0 PG 16 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA UE843 UT WOS:A1996UE84300002 PM 8935954 ER PT J AU Heermeier, K Benedict, M Li, ML Furth, P Nunez, G Henninghausen, L AF Heermeier, K Benedict, M Li, ML Furth, P Nunez, G Henninghausen, L TI Bax and Bcl-x(S) are induced at the onset of apoptosis in involuting mammary epithelial cells SO MECHANISMS OF DEVELOPMENT LA English DT Article DE Bax; Bcl-x(S); apoptosis; mammary gland involution ID DEATH; GLAND; PROTEIN; BCL-2; GENE; MICE; BREAST AB Mammary gland involution is a physiological process in which the entire organ is remodeled through the process of apoptosis. Apoptosis of secretory alveolar cells is initiated at the time of weaning, followed by the collapse and disappearance of the entire lobuloalveolar compartment. While apoptotic figures were rare in mammary epithelium of lactating mice, their number increased after weaning and reached a maximum on day 3 of involution. Active cell death continued until day 5 after weaning and only little parenchyma remained on day 8, when remodeling of the gland was completed. Bax mRNA levels increased during the first day of involution independent of the presence or absence of p53. Bax protein was detected in an increasing number of cells after weaning, peaking at day 3 and decreasing thereafter. Low levels of bcl-x mRNA and protein were present during lactation, followed by a sharp increase during the first 2 days of involution. The bcl-x(S) splice variant of bcl-x can promote cell death, and bcl-x(L) has a protective function in cell culture. The ratio of bcl-x(S) versus bcl-x(L) remained stable in the virgin, pregnant and lactating gland. However, during the first 2 days of involution, bcl-x(S) expression increased six-fold more than bcl-x(L). To further evaluate the role of Bcl-x(S) which was less abundant in the mammary cells than Bcl-x(L), cotransfection studies were performed in cell culture. They confirmed that Bcl-x(S) protein can facilitate apoptosis even when Bcl-x(L) is present in excess. These findings point to a significant role for Bax and Bcl-x(S) in the regulation of apoptosis of secretory alveolar cells during involution. C1 NIDDKD, BIOCHEM & METAB LAB, NIH, BETHESDA, MD 20892 USA. UNIV MICHIGAN, SCH MED, DEPT PATHOL, ANN ARBOR, MI 48109 USA. UNIV MARYLAND, SCH MED, DEPT MED, DIV INFECT DIS, BALTIMORE, MD 21201 USA. BALTIMORE VET AFFAIRS MED CTR, BALTIMORE, MD 21201 USA. FU NCI NIH HHS [CA 64556, K04 CA 64421] NR 45 TC 104 Z9 110 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 EI 1872-6356 J9 MECH DEVELOP JI Mech. Dev. PD MAY PY 1996 VL 56 IS 1-2 BP 197 EP 207 DI 10.1016/0925-4773(96)88032-4 PG 11 WC Developmental Biology SC Developmental Biology GA UT141 UT WOS:A1996UT14100016 PM 8798158 ER PT J AU Doubt, TJ AF Doubt, TJ TI Cardiovascular and thermal responses to SCUBA diving SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE exercise; adaptation; hyperbaric; heart rate; thermal balance; immersion ID COLD WATER; HEART-RATE; EXERCISE; IMMERSION AB Recreational SCUBA diving exposes individuals to environmental stresses not often encountered in other types of activity. These stresses include increased ambient pressure, raised partial pressure of O-2, increased resistance to movement, added weight and drag of diving equipment, cold stress, and a higher breathing resistance. One means to understand how such stresses affect a diver is to employ the stress-strain-adaptive response model. Physiologic adaptations, like an increase in VO2 in response to cold stress, will minimize the strain placed on thermal balance. Nonphysiologic adaptive responses include those behavioral and equipment interventions that isolate the diver from a particular stress. Self-contained underwater breathing apparatus (SCUBA) isolates the diver from the inability to extract O-2 from the water; dive garments minimize the stress of cold water immersion. This review will focus on cardiorespiratory and thermal responses to SCUBA diving, using the stress-strain-adaptive response model to illustrate the interaction between diver and environment. Some responses like hyperventilation, cardiac arrhythmias, or cold injury due to vasoconstriction;are not considered adaptive but are realistic possibilities in diving environments. RP Doubt, TJ (reprint author), NHLBI,DIV HEART & VASC DIS,BETHESDA,MD 20892, USA. NR 25 TC 18 Z9 18 U1 4 U2 12 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 1996 VL 28 IS 5 BP 581 EP 586 DI 10.1097/00005768-199605000-00007 PG 6 WC Sport Sciences SC Sport Sciences GA UG989 UT WOS:A1996UG98900007 PM 9148087 ER PT J AU Trainor, CD Omichinski, JG Vandergon, TL Gronenborn, AM Clore, GM Felsenfeld, G AF Trainor, CD Omichinski, JG Vandergon, TL Gronenborn, AM Clore, GM Felsenfeld, G TI A palindromic regulatory site within vertebrate GATA-1 promoters requires both zinc fingers of the GATA-1 DNA-binding domain for high-affinity interaction SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ERYTHROID TRANSCRIPTION FACTOR; FACTOR FAMILY; FACTOR NF-E1; GLOBIN GENE; EXPRESSION; CELLS; PROTEIN; DIFFERENTIATION; SPECIFICITY; SEQUENCE AB GATA-1, a transcription factor essential for the development of the erythroid lineage, contains two adjacent highly conserved zinc finger motifs. The carboxy-terminal finger is necessary and sufficient for specific binding to the consensus GATA recognition sequence: mutant proteins containing only the amino-terminal finger do not bind. Here we identify a DNA sequence (GATApal) for which the GATA-1 amino-terminal finger makes a critical contribution to the strength of binding. The site occurs in the GATA-1 gene promoters of chickens, mice, and humans but occurs very infrequently in other vertebrate genes known to be regulated by GATA proteins. GATApal is a palindromic site composed of one complete [(AIT)GATA(A/G)] and one partial (GAT) canonical motif. Deletion of the partial motif changes the site to a normal GATA site and also reduces by as much as eightfold the activity of the GATA-1 promoter in an erythroid precursor cell, We propose that GATApal is important for positive regulation of GATA-1 expression in erythroid cells. C1 NIDDK,MOLEC BIOL LAB,BETHESDA,MD 20892. NIDDK,CHEM PHYS LAB,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 42 TC 160 Z9 163 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1996 VL 16 IS 5 BP 2238 EP 2247 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UG299 UT WOS:A1996UG29900037 PM 8628290 ER PT J AU Duncan, R Collins, I Tomonaga, T Zhang, T Levens, D AF Duncan, R Collins, I Tomonaga, T Zhang, T Levens, D TI A unique transactivation sequence motif is found in the carboxyl-terminal domain of the single-strand-binding protein FBP SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RICH ACTIVATION MOTIF; TRANSCRIPTIONAL ACTIVATOR; MAMMALIAN-CELLS; MECHANISM; DNA AB The far-upstream element-binding protein (FBP) is one of several recently described factors which bind to a single strand of DNA in the 5' region of the c-myc gene. Although cotransfection of FBP increases expression from a far-upstream element-bearing c-myc promoter reporter, the mechanism of this stimulation is heretofore unknown, Can a single-strand-binding protein function as a classical transactivator, or are these proteins restricted to stabilizing or altering the conformation of DNA in an architectural role? Using chimeric GAL4-FBP fusion proteins we have shown that the carboxyl-terminal region (residues 448 to 644) is a potent transcriptional activation domain. This region contains three copies of a unique amino acid sequence motif containing tyrosine diads, Analysis of deletion mutants demonstrated that a single tyrosine motif alone (residues 609 to 644) was capable of activating transcription. The activation property of the C-terminal domain is repressed by the N-terminal 107 amino acids of FBP, These results show that FBP contains a transactivation domain which can function alone, suggesting that FBP contributes directly to c-myc transcription while bound to a single-strand site. Furthermore, activation is mediated by a new motif which can be negatively regulated by a repression domain of FBP. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. RI Levens, David/C-9216-2009; Duncan, Robert/I-8168-2015 OI Levens, David/0000-0002-7616-922X; Duncan, Robert/0000-0001-8409-2501 NR 34 TC 55 Z9 55 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1996 VL 16 IS 5 BP 2274 EP 2282 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UG299 UT WOS:A1996UG29900041 PM 8628294 ER PT J AU Gontarek, RR Derse, D AF Gontarek, RR Derse, D TI Interactions among SR proteins, an exonic splicing enhancer, and a lentivirus Rev protein regulate alternative splicing SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SMALL NUCLEAR RIBONUCLEOPROTEIN; MESSENGER-RNA; PREMESSENGER RNA; INTRONIC SEQUENCES; CONSERVED FAMILY; SITE SELECTION; POLYMERASE-II; INVITRO; GENE; BINDING AB We examine here the roles of cellular splicing factors and virus regulatory proteins in coordinately regulating alternative splicing of the tat/rev mRNA of equine infectious anemia virus (EIAV). This bicistronic mRNA contains four exons; exons 1 and 2 encode rat, and exons 3 and 4 encode Rev. In the absence of Rev expression, the four-exon mRNA is synthesized exclusively, but when Rev is expressed, exon 3 is skipped to produce an mRNA that contains only exons 1, 2, and 4. We identify a purine-rich exonic splicing enhancer (ESE) in exon 3 that promotes exon inclusion. Similar to other cellular ESEs that have been identified by other laboratories, the EIAV ESE interacted specifically with SR proteins, a group of serine/arginine-rich splicing factors that function in constitutive and alternative mRNA splicing, Substitution of purines with pyrimidines in the ESE resulted in a switch from exon inclusion to exon skipping in vivo and abolished binding of SR proteins in vitro. Exon skipping was also induced by expression of EIAV Rev. We show that Rev binds to exon 3 RNA in vitro, and while the precise determinants have not been mapped, Rev function in vivo and RNA binding in vitro indicate that the RNA element necessary for Rev responsiveness overlaps or is adjacent to the ESE. We suggest that EIAV Rev promotes exon skipping by interfering with SR protein interactions with RNA or with other splicing factors. C1 NCI,FREDERICK CANC RES & DEV CTR,LAB LEUKOCYTE BIOL,FREDERICK,MD 21702. NR 56 TC 51 Z9 51 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1996 VL 16 IS 5 BP 2325 EP 2331 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UG299 UT WOS:A1996UG29900046 PM 8628299 ER PT J AU Klement, JF Rice, NR Car, BD Abbondanzo, SJ Powers, GD Bhatt, H Chen, CH Rosen, CA Stewart, CL AF Klement, JF Rice, NR Car, BD Abbondanzo, SJ Powers, GD Bhatt, H Chen, CH Rosen, CA Stewart, CL TI I kappa B alpha deficiency results in a sustained NF-kappa B response and severe widespread dermatitis in mice SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; NUCLEAR-LOCALIZATION SIGNAL; DNA-BINDING SUBUNIT; C-REL PROMOTER; CYTOPLASMIC RETENTION; TRANSCRIPTION FACTOR; TRANSGENIC MICE; P50 SUBUNIT; V-REL; ACTIVATION AB The ubiquitous transcription factor NF-kappa B is an essential component in signal transduction pathways, in inflammation, and in the immune response, NF-kappa B is maintained in an inactive state in the cytoplasm by protein-protein interaction with I kappa B alpha. Upon stimulation, rapid degradation of I kappa B alpha allows nuclear translocation of NF-kappa B. To study the importance of I kappa B alpha in signal transduction, I kappa B alpha-deficient mice mere derived by gene targeting, Cultured fibroblasts derived from I kappa B alpha-deficient embryos exhibit levels of NF-kappa B1, NF-kappa B2, RelA, c-Rel, and I kappa B beta similar to those of wild-type fibroblasts, A failure to increase nuclear levels of NF-kappa B indicates that cytoplasmic retention of NF-kappa B may be compensated for by other I kappa B proteins. Treatment of wild-type cells with tumor necrosis factor alpha (TNF-alpha) resulted in rapid, transient nuclear localization of NF-kappa B. I kappa B alpha-deficient fibroblasts are also TNF-alpha responsive, but nuclear localization of NF-kappa B is prolonged, thus demonstrating that a major irreplaceable function of I kappa B alpha is termination of the NF-kappa B response, Consistent with these observations, and with I kappa B alpha and NF-kappa B's role in regulating inflammatory and immune responses, is the normal development of I kappa B alpha-deficient mice. However, growth ceases 3 days after birth and death usually occurs at 7 to 10 days of age. An increased percentage of monocytes/macrophages was detected in spleen cells taken from 5-, 7-, and 9-day-old pups, Death is accompanied by severe widespread dermatitis and increased levels of TNF-alpha mRNA in the skin. C1 ROCHE INST MOLEC BIOL,ROCHE RES CTR,NUTLEY,NJ 07110. HOFFMANN LA ROCHE INC,NUTLEY,NJ 07110. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. DUPONT CO INC,STINE HASKELL RES CTR,RES & DEV,NEWARK,DE 19714. NR 65 TC 251 Z9 260 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1996 VL 16 IS 5 BP 2341 EP 2349 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UG299 UT WOS:A1996UG29900048 PM 8628301 ER PT J AU Michelotti, EF Michelotti, GA Aronsohn, AI Levens, D AF Michelotti, EF Michelotti, GA Aronsohn, AI Levens, D TI Heterogeneous nuclear ribonucleoprotein K is a transcription factor SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN C-MYC; TATA-BINDING PROTEIN; SINGLE-STRANDED-DNA; 5S RNA GENE; ESCHERICHIA-COLI; RIBOSOMAL-RNA; CHROMATIN STRUCTURE; STEP PURIFICATION; ACTIVATION; EXPRESSION AB The CT element is a positively acting homopyrimidine tract upstream of the c-myc gene to which the well-characterized transcription factor Spl and heterogeneous nuclear ribonucleoprotein (hnRNP) K, a less well-characterized protein associated with hnRNP complexes, have previously been shown to bind, The present work demonstrates that both of these molecules contribute to CT element-activated transcription in vitro, The pyrimidine-rich strand of the CT element both bound to hnRNP K and competitively inhibited transcription in vitro, suggesting a role for hnRNP K in activating transcription through this single-stranded sequence, Direct addition of recombinant hnRNP K to reaction mixtures programmed with templates bearing single-stranded CT elements increased specific RNA synthesis. If hnRNP K is a transcription factor, then interactions with the RNA polymerase II transcription apparatus are predicted, Affinity columns charged with recombinant hnRNP K specifically bind a component(s) necessary for transcription activation. The depleted factors were biochemically complemented by a crude TFIID phosphocellulose fraction, indicating that hnRNP K might interact with the TATA-binding protein (TBP)-TBP-associated factor complex. coimmunoprecipitation of a complex formed in vivo between hnRNP K and epitope-tagged TBP as well as binding in vitro between recombinant proteins demonstrated a protein-protein interaction between TBP and hnRNP K, Furthermore, when the two proteins were overexpressed in vivo, transcription from a CT element-dependent reporter was synergistically activated. These data indicate that hnRNP K binds to a specific cis element, interacts with the RNA polymerase II transcription machinery, and stimulates transcription and thus has all of the properties of a transcription factor. C1 NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X NR 72 TC 268 Z9 274 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1996 VL 16 IS 5 BP 2350 EP 2360 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UG299 UT WOS:A1996UG29900049 PM 8628302 ER PT J AU Nakayama, M Stauffer, J Cheng, J BanerjeeBasu, S Wawrousek, E Buonanno, A AF Nakayama, M Stauffer, J Cheng, J BanerjeeBasu, S Wawrousek, E Buonanno, A TI Common core sequences are found in skeletal muscle slow- and fast-fiber-type-specific regulatory elements SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TROPONIN-I GENE; HUMAN MYOGLOBIN PROMOTER; TRANSGENIC MICE; TRANSCRIPTION FACTORS; BINDING-FACTOR; MYOD FAMILY; EXPRESSION; ENHANCER; RAT; MYOGENIN AB The molecular mechanisms generating muscle diversity during development are unknown, The phenotypic properties of slow- and fast-twitch myofibers are determined by the selective transcription of genes coding for contractile proteins and metabolic enzymes in these muscles, properties that fail to develop in cultured muscle, Using transgenic mice, we have identified regulatory elements in the evolutionarily related troponin slow (TnIs) and fast (TnIf) genes that confer specific transcription in either slow or fast muscles, Analysis of serial deletions of the rat TnIs upstream region revealed that sequences between kb -0.95 and -0.5 are necessary to confer slow-fiber-specific transcription; the -0.5-kb fragment containing the basal promoter was inactive in five transgenic mouse lines tested, We identified a 128-bp regulatory element residing at kb -0.8 that, when linked to the -0.5-kb TnIs promoter, specifically confers transcription to slow-twitch muscles, To identify sequences directing fast-fiber-specific transcription, we generated transgenic mice harboring a construct containing the TnIs kb -0.5 promoter fused to a 144-bp enhancer derived from the quail TnIf gene, Mice harboring the TnIf/TnIs chimera construct expressed the transgene in fast but not in slow muscles, indicating that these regulatory elements are sufficient to confer fiber-type-specific transcription, Alignment of rat TnIs and quail TnIf regulatory sequences indicates that there is a conserved spatial organization of core elements, namely, an E box, a CCAC box, a MEF-2-like sequence, and a previously uncharacterized motif, The core elements were shown to bind their cognate factors by electrophoretic mobility shift assays, and their mutation demonstrated that the TnIs CCAC and E boxes are necessary for transgene expression, Our results suggest that the interaction of closely related transcriptional protein-DNA complexes is utilized to specify fiber type diversity. C1 NICHHD,MOLEC NEUROBIOL UNIT,NIH,BETHESDA,MD 20892. NEI,BETHESDA,MD 20892. RI Wawrousek, Eric/A-4547-2008 FU NICHD NIH HHS [N01-HD-0-2911] NR 61 TC 69 Z9 70 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1996 VL 16 IS 5 BP 2408 EP 2417 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UG299 UT WOS:A1996UG29900056 PM 8628309 ER PT J AU Yenush, L Fernandez, R Myers, MG Grammer, TC Sun, XJ Blenis, J Pierce, JH Schlessinger, J White, MF AF Yenush, L Fernandez, R Myers, MG Grammer, TC Sun, XJ Blenis, J Pierce, JH Schlessinger, J White, MF TI The Drosophila insulin receptor activates multiple signaling pathways but requires insulin receptor substrate proteins for DNA synthesis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DEPENDENT HEMATOPOIETIC-CELLS; PHOSPHATIDYLINOSITOL 3'-KINASE; TYROSINE PHOSPHORYLATION; IRS-1; KINASES; TRANSDUCTION; ASSOCIATION; BINDS; GRB2 AB The Drosophila insulin receptor (DIR) contains a 368-amino-acid COOH-terminal extension that contains several tyrosine phosphorylation sites in YXXM motifs, This extension is absent from the human insulin receptor but resembles a region in insulin receptor substrate (IRS) proteins which binds to the phosphatidylinositol (PI) 3-kinase and mediates mitogenesis, The function of a chimeric DIR containing the human insulin receptor binding domain (hDIR) was investigated in 32D cells, which contain few insulin receptors and no IRS proteins. Insulin stimulated tyrosine autophosphorylation of the human insulin receptor and hDIR, and both receptors mediated tyrosine phosphorylation of She and activated mitogen-activated protein kinase, IRS-1 was required by the human insulin receptor to activate PI 3-kinase and p70(s6k), whereas hDIR associated with PI 3-kinase and activated p70(s6k) without IRS-I, However, both receptors required IRS-1 to mediate insulin-stimulated mitogenesis. These data demonstrate that the DIR possesses additional signaling capabilities compared with its mammalian counterpart but still requires IRS-1 for the complete insulin response in mammalian cells. C1 JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,PROGRAM BIOMED & BIOL SCI,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02215. NYU,MED CTR,DEPT PHARMACOL,NEW YORK,NY 10016. NIH,LAB CELL & MOL BIOL,BETHESDA,MD 20892. RI Yenush, Lynne/J-8815-2014 OI Yenush, Lynne/0000-0001-8589-7002 FU NCI NIH HHS [CA46595]; NIDDK NIH HHS [DK43808, DK38712] NR 41 TC 62 Z9 62 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1996 VL 16 IS 5 BP 2509 EP 2517 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UG299 UT WOS:A1996UG29900066 PM 8628319 ER PT J AU Thomas, DC Svoboda, DL Vos, JMH Kunkel, TA AF Thomas, DC Svoboda, DL Vos, JMH Kunkel, TA TI Strand specificity of mutagenic bypass replication of DNA containing psoralen monoadducts in a human cell extract SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INTERSTRAND CROSS-LINKS; UV-INDUCED MUTATIONS; MOLECULAR ANALYSIS; REPAIR-PROFICIENT; HUMAN-FIBROBLASTS; DAMAGED DNA; HPRT GENE; FIDELITY; ADDUCTS; 8-METHOXYPSORALEN AB Psoralens are mutagenic compounds of vegetable origin that are used as photosensitizing agents in the treatment of various skin diseases, blood cell cancer, and autoimmune disorders, To study the mechanism of mutagenicity of psoralens in humans, we examined the eaciency and fidelity of simian virus 40 origin-dependent replication in a human cell extract of M13mp2 DNA randomly treated with the psoralen derivative 4'-hydroxymethyl-4,5',8-trimethyl psoralen plus WA irradiation, Replication of DNA treated with variable amounts of 4'-hydroxymethyl-3,5',8-trimethyl psoralen and a fixed WA fluence was inhibited in a concentration-dependent manner, However, covalently closed monomer-length circular replication products were observed. Product analysis by renaturing agarose gel electrophoresis after cross-linking with 250- to 280-nm UV light indicated that approximately 1 of 9 psoralen monoadducts was bypassed during in vitro replication, Introduction of product DNA into Escherichia coli to score replication errors in the lacZ alpha reporter gene demonstrated that replication of the damaged DNA was more mutagenic than was replication of undamaged DNA, Sequence analysis of lacZ mutants revealed that damage-dependent replication errors were predominantly T . A-->C . G transitions, transversions at C . G base pairs, and deletions of single A . T base pairs, the last occurring most frequently in homopolymeric runs, A comparison of error specificities with two substrates having the replication origin asymmetrically placed on opposite sides of the mutational target suggests that the lagging-strand replication apparatus is less accurate than the leading-strand replication apparatus for psoralen monoadduct-dependent deletion errors, A model is proposed based on the preferential loopout of the monoadducted base from the strand that templates retrograde discontinuous synthesis. C1 UNIV N CAROLINA,SCH MED,UNC LINEBERGER COMPREHENS CANC CTR,CHAPEL HILL,NC 27599. NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,DEPT BIOCHEM & BIOPHYS,CHAPEL HILL,NC 27599. FU NCI NIH HHS [1-R01-CA51096] NR 54 TC 22 Z9 22 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1996 VL 16 IS 5 BP 2537 EP 2544 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UG299 UT WOS:A1996UG29900069 PM 8628322 ER PT J AU Ranjan, M Hudson, LD AF Ranjan, M Hudson, LD TI Regulation of tyrosine phosphorylation and protein tyrosine phosphatases during oligodendrocyte differentiation SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID LEUKOCYTE-COMMON-ANTIGEN; CENTRAL-NERVOUS-SYSTEM; CDNA CLONING; EXTRACELLULAR REGION; RAT-BRAIN; EXPRESSION; CELLS; MOUSE; IDENTIFICATION; FAMILY AB Tyrosine phosphorylation is key to the differentiation of oligodendrocytes, as the FGF2 and PDGF receptor tyrosine kinases are known to mediate the proliferation and maintenance of their precursors. Marked changes in the levels and localization of tyrosine-phosphorylated proteins were found to accompany differentiation in the CG4 rat oligodendrocyte cell line. These alterations in phosphorylation as well as other differentiation-specific changes were found to be sensitive to inhibition by a tyrosine phosphatase inhibitor. This suggested that at some point early in the differentiation process, tyrosine phosphatases are important. A differential display strategy revealed 11 distinct tyrosine phosphatases in the oligodendrocyte lineage, with both precursor cells and oligodendrocytes expressing four major phosphatase transcripts: PTP alpha, PTP zeta, PTP sigma, and PTP gamma. A majority of the phosphatases examined show an increase in their mRNA levels during differentiation, with a striking upregulation observed for PTP epsilon. Our results suggest a significant role for this class of signal transducers in oligodendrocyte differentiation. RP Ranjan, M (reprint author), NINCDS,LAB DEV NEUROGENET,NIH,BLDG 36,RM 5D05,BETHESDA,MD 20892, USA. NR 62 TC 31 Z9 31 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell Neurosci. PD MAY PY 1996 VL 7 IS 5 BP 404 EP 418 DI 10.1006/mcne.1996.0029 PG 15 WC Neurosciences SC Neurosciences & Neurology GA UX913 UT WOS:A1996UX91300005 PM 8812065 ER PT J AU Colton, C Wilt, S Gilbert, D Chernyshev, O Snell, J DuboisDalcq, M AF Colton, C Wilt, S Gilbert, D Chernyshev, O Snell, J DuboisDalcq, M TI Species differences in the generation of reactive oxygen species by microglia SO MOLECULAR AND CHEMICAL NEUROPATHOLOGY LA English DT Article; Proceedings Paper CT Symposium on Neurodegenerative Disorders - Common Molecular Mechanisms CY APR 02-07, 1995 CL OCHO RIOS, JAMAICA SP Univ Goteborg, Sweden, Univ West Indies, Kingston, Jamaica DE macrophages; microglia; reactive oxygen species; Alzheimer disease; inflammation; superoxide anion; nitric oxide ID CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; END-PRODUCTS; HUMAN-BRAIN; PEROXIDATION; MACROPHAGES; METABOLISM; CELLS AB Although a variety of potential sources for reactive oxygen species (ROS) exist in the CNS, brain macrophages, i.e., the microglia, generate large quantities of these reactive species, particularly in response to injury or inflammatory signals. In order to understand how microglia contribute to changes in oxidative status of the CNS and how this might relate to disease states, such as Alzheimer disease (AD), we have examined the regulation of superoxide anion and nitric oxide production from rodent and human microglia. Our results indicate that microglia from all species we have studied release superoxide anion, but produce significantly different amounts in response to the same activating agents. Species differences are also found in the ability to generate nitric oxide (NO). In particular, mouse microglia generate large quantities of NO when stimulated, but human and hamster microglia do not produce measurable amounts under the same stimulation conditions. These species differences are important to consider when modeling human disease processes from rodent studies. C1 INST PASTEUR,DEPT VIROL,PARIS,FRANCE. NINCDS,UNIT REACT OXYGEN SPECIES,BIOPHYS SECT,NIH,BETHESDA,MD 20892. RP Colton, C (reprint author), GEORGETOWN UNIV,SCH MED,DEPT PHYSIOL & BIOPHYS,WASHINGTON,DC 20007, USA. NR 18 TC 76 Z9 76 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 1044-7393 J9 MOL CHEM NEUROPATHOL JI Mol. Chem. Neuropathol. PD MAY-AUG PY 1996 VL 28 IS 1-3 BP 15 EP 20 DI 10.1007/BF02815200 PG 6 WC Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA VC268 UT WOS:A1996VC26800003 PM 8871937 ER PT J AU Kusiak, JW Izzo, JA Zhao, BY AF Kusiak, JW Izzo, JA Zhao, BY TI Neurodegeneration in Alzheimer disease - Is apoptosis involved? SO MOLECULAR AND CHEMICAL NEUROPATHOLOGY LA English DT Article; Proceedings Paper CT Symposium on Neurodegenerative Disorders - Common Molecular Mechanisms CY APR 02-07, 1995 CL OCHO RIOS, JAMAICA SP Univ Goteborg, Sweden, Univ West Indies, Kingston, Jamaica DE Alzheimer disease; apoptosis; neurodegeneration; programmed cell death; gene expression; beta-amyloid; amyloid precursor protein ID AMYLOID PRECURSOR PROTEIN; PROGRAMMED CELL-DEATH; NEURONAL APOPTOSIS; TRANSGENIC MICE; MISSENSE MUTATION; CORTICAL-NEURONS; NERVOUS-SYSTEM; BETA; PEPTIDE; NEUROTOXICITY AB Alzheimer disease (AD), the most common dementia of the elderly, results from a significant loss of neuronal cells in brain regions important in memory and cognition. Several lines of evidence suggest that the A beta peptide is directly responsible for some of this neuronal cell death. We review recent evidence from in vitro toxicity and immunohistochemical studies that suggest some of the cell loss in AD is the result of apoptosis. RP Kusiak, JW (reprint author), NIA,MOL NEUROBIOL UNIT,GERONTOL RES CTR,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 41 TC 28 Z9 28 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 1044-7393 J9 MOL CHEM NEUROPATHOL JI Mol. Chem. Neuropathol. PD MAY-AUG PY 1996 VL 28 IS 1-3 BP 153 EP 162 DI 10.1007/BF02815217 PG 10 WC Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA VC268 UT WOS:A1996VC26800020 PM 8871954 ER PT J AU Jucker, M Min, TA Ingram, DK AF Jucker, M Min, TA Ingram, DK TI Laminins in the adult and aged brain SO MOLECULAR AND CHEMICAL NEUROPATHOLOGY LA English DT Article; Proceedings Paper CT Symposium on Neurodegenerative Disorders - Common Molecular Mechanisms CY APR 02-07, 1995 CL OCHO RIOS, JAMAICA SP Univ Goteborg, Sweden, Univ West Indies, Kingston, Jamaica DE basement membrane; extracellular matrix; vasculature; blood vessel; astrocyte; endothelial cell; aging; Alzheimer disease; CNS; lesion, injury ID CENTRAL-NERVOUS-SYSTEM; VASCULAR BASEMENT-MEMBRANE; ALZHEIMERS-DISEASE; EXTRACELLULAR-MATRIX; RAT HIPPOCAMPUS; BASAL LAMINA; COLLAGEN-IV; S-LAMININ; B2 CHAIN; EXPRESSION AB Only recently have we become aware of the diversity of laminins in adult brain. In vascular basement membranes, the expression of at least five laminin chains has been demonstrated, suggesting the presence of several laminin variants. Recent ultrastructural evidence for heterogeneity of laminin expression in vascular basement membranes is an exciting finding, and points to structural and functional diversity of the basement membranes around cerebral blood vessels. Neuronal laminin-like immunoreactivity in the adult brain is a consistent observation, but does not fit well in the current understanding of the physiology and biochemistry of heterotrimeric laminins. Nevertheless, the unique localization of putative neuronal laminins warrants their further characterization. The structure and function of laminins produced by reactive astrocytes in the lesioned adult brain and that seen in the brains of Alzheimer disease (AD) patients are not yet resolved. The possibility that these laminins play an important role in the CNS response to injury and pathophysiology of AD is expected to be a fruitful investigation. The next decade should see very significant advances in the characterization of brain laminins and, hopefully, in the elucidation of functional correlates to the structural diversity of laminins in brain. RP Jucker, M (reprint author), NIA,GERONTOL RES CTR,NIH,MOL & CELLULAR BIOL LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 44 TC 37 Z9 38 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 1044-7393 J9 MOL CHEM NEUROPATHOL JI Mol. Chem. Neuropathol. PD MAY-AUG PY 1996 VL 28 IS 1-3 BP 209 EP 218 DI 10.1007/BF02815224 PG 10 WC Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA VC268 UT WOS:A1996VC26800027 PM 8871961 ER PT J AU RodgersJohnson, PEB Hickling, FW Irons, A Johnson, BK IronsMorgan, M Stone, GA Gibbs, CJ AF RodgersJohnson, PEB Hickling, FW Irons, A Johnson, BK IronsMorgan, M Stone, GA Gibbs, CJ TI Retroviruses and schizophrenia in Jamaica SO MOLECULAR AND CHEMICAL NEUROPATHOLOGY LA English DT Article; Proceedings Paper CT Symposium on Neurodegenerative Disorders - Common Molecular Mechanisms CY APR 02-07, 1995 CL OCHO RIOS, JAMAICA SP Univ Goteborg, Sweden, Univ West Indies, Kingston, Jamaica DE schizophrenia; virus; HTLV-I; Afro-Caribbeans ID VIRUS TYPE-I; PRENATAL EXPOSURE; AFRO-CARIBBEANS; HTLV-I; INFLUENZA EPIDEMIC; ADMISSION RATES; CAMBERWELL; IMMIGRANTS; LONDON AB Reports of an 18-fold higher incidence of schizophrenia among second-generation Afro-Caribbeans, and especially Jamaican migrants in the United Kingdom were soon called ''an epidemic of schizophrenia,'' with the inference that a novel virus, likely to be perinatally transmitted, was a possible etiological agent. This intriguing observation led us to explore a possible link with human T-cell lymphotropic virus type one (HTLV-I), because it is a virus that is endemic in the Caribbean Islands, is perinatally transmitted, known to be neuropathogenic, and the cause of a chronic myelopathy (tropical spastic paraparesis/ HTLV-I associated myelopathy). We therefore examined inpatients at the Bellevue Mental Hospital, Kingston, Jamaica and did standard serological tests for retroviruses HTLV-I and HTLV-II and HIV-I and HIV-II on 201 inpatients who fulfilled ICD-9 and DSM III-R criteria for schizophrenia. Our results produced important negative data, since the seropositivity rates for HTLV-I, the most likely pathogen, were no greater than the seropositivity range for HTLV-I carriers in this island population indicating that HTLV-I and the other retroviruses tested do not play a primary etiological role in Jamaican schizophrenics. C1 PSYCHOTHERAPY ASSOCIATES,KINGSTON,JAMAICA. BELLVITGE HOSP,KINGSTON,JAMAICA. NIH,CENT NERVOUS SYST STUDIES LAB,BETHESDA,MD 20892. RP RodgersJohnson, PEB (reprint author), UNIV W INDIES,DEPT MED,KINGSTON 7,JAMAICA. NR 23 TC 4 Z9 4 U1 2 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 1044-7393 J9 MOL CHEM NEUROPATHOL JI Mol. Chem. Neuropathol. PD MAY-AUG PY 1996 VL 28 IS 1-3 BP 237 EP 243 DI 10.1007/BF02815228 PG 7 WC Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA VC268 UT WOS:A1996VC26800031 PM 8871965 ER PT J AU Modi, WS AF Modi, WS TI Phylogenetic history of LINE-1 among arvicolid rodents SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE LINE-1; arvicolid rodent evolution; phylogenetic reconstruction ID L1 REPEAT FAMILY; CONCERTED EVOLUTION; DNA FAMILY; MICE; HETEROGENEITY; SEQUENCE; PATTERNS; MICROTUS; ELEMENT AB The extent of restriction fragment sharing among arvicolid rodents was examined following Southern blotting with a reverse transcriptase region probe from long interspersed nuclear element 1 (LINE-1 or L1). DNAs from 30 species belonging to nine genera were digested with 11 restriction endonucleases. Following hybridization discrete bands were scored with respect to their presence or absence and intensity, and both within- and between-species comparisons were conducted. Intraspecific analyses revealed low but detectable levels of variation. Interspecific comparisons revealed three groups of bands: those present in all 30 species (6 out of a total of 248 bands), those phylogenetically informative in two or more species (130 out of 248), and those unique to a single species (114 out oi 248). A multistate data matrix consisting of species by codes representing the intensities of informative bands was analyzed by maximum parsimony. Further, distance values between species were converted to rates using estimated fossil divergence times. Both the parsimony and rate analyses revealed differences between species in the extent of band sharing and in the intensities of common bands, indicating that the amplification and movement of LINE elements has occurred in episodic bursts during the history of this group. Systematic interpretations of the evolutionary trees were concordant with those previously obtained using other data sets, suggesting that although the amplification of repetitive sequences may occur episodically in this taxonomic group, there do appear to be some constraints. RP Modi, WS (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702, USA. NR 31 TC 26 Z9 28 U1 0 U2 0 PU SOC MOLECULAR BIOLOGY EVOLUTION PI LAWRENCE PA PO BOX 1897, LAWRENCE, KS 66044-8897 SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD MAY PY 1996 VL 13 IS 5 BP 633 EP 641 PG 9 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA UH905 UT WOS:A1996UH90500001 PM 8676737 ER PT J AU Spillare, EA Okamoto, A Hagiwara, K Demetrick, DJ Serrano, M Beach, D Harris, CC AF Spillare, EA Okamoto, A Hagiwara, K Demetrick, DJ Serrano, M Beach, D Harris, CC TI Suppression of growth in vitro and tumorigenicity in vivo of human carcinoma cell lines by transfected p16(INK4) SO MOLECULAR CARCINOGENESIS LA English DT Article DE cyclin-dependent kinase inhibitor; tumor suppression; CDKN2; MTS-1 ID RETINOBLASTOMA AB The function of p16(INK4) as a putative tumor suppressor gene was examined by investigating its ability to inhibit the growth of cancer cell lines in vitro and tumor formation in vivo. A p16(INK4) cDNA expression vector was transfected into five human cancer cell lines that varied in their p16(INK4) and retinoblastoma (Rb) status. Suppression of colony-forming efficiency was seen in four cell lines. Of two cell lines wild type for p16(INK4) but null for Rb protein expression, one (Hep 3B) showed inhibition of colony formation, whereas the other (Saos-2) did not. This observation may demonstrate involvement of p16(INK4) independent of Rb. The transfected p16(INK4) gene was frequently selected against and lost during continued growth in vitro. When compared to the colon carcinoma cell line (DLD-1), p16(INK4)-transfected DLD-1 clone 1 cells were less tumorigenic in athymic nude mice. Tumors arising from p16(INK4)-transfected DLD-1 clones, which were growth suppressed in vitro, either lost the integrated exogenous p16(INK4) or expressed reduced amounts of p16(INK4) protein. Therefore, p16(INK4) was also selected against during tumor formation in vivo. These data are consistent with the hypothesis that p16(INK4) isa tumor suppressor gene. (C) 1996 Wiley-Liss, Inc. C1 NCI,HUMAN CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. COLD SPRING HARBOR LAB,COLD SPRING HARBOR,NY 11724. RI Serrano, Manuel/H-2634-2015 OI Serrano, Manuel/0000-0001-7177-9312 NR 49 TC 36 Z9 37 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD MAY PY 1996 VL 16 IS 1 BP 53 EP 60 DI 10.1002/(SICI)1098-2744(199605)16:1<53::AID-MC7>3.0.CO;2-P PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA UL498 UT WOS:A1996UL49800007 PM 8634094 ER PT J AU Collier, CD Oshima, H Simons, SS AF Collier, CD Oshima, H Simons, SS TI A negative tyrosine aminotransferase gene element that blocks glucocorticoid modulatory element-regulated modulation of glucocorticoid-induced gene expression SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID MOUSE ALBUMIN ENHANCER; BINDING-SITE; RESPONSIVE ELEMENTS; HEPATOMA-CELLS; TRANSCRIPTION; SILENCER; PROMOTER; INDUCTION; RECEPTOR; IDENTIFICATION AB Tyrosine aminotransferase (TAT) is the prototypic steroid-inducible gene. Recently, we have found that the modulation of TAT induction properties is reproduced by a novel cis-acting TAT gene element, the glucocorticoid modulatory element (GME). This GME lies about 1 kb upstream of the glucocorticoid response elements (GREs) of the TAT gene and binds a heterooligomer of two recently defined proteins. We now report the existence of an additional TAT gene element between the GME and the GREs that blocks the action of the GME and thus prevents the left shift in the glucocorticoid dose-response curve caused by the GME. This negative element has the properties of a silencer because its activity is relatively position- and orientation-independent. The interaction appears to be stoichiometric in that the effects of a single negative element can be overcome by a second GME. This negative element also has an intrinsic inhibitory activity in the absence of the GME. The majority of the negative element activity could be elicited by a 56-bp sequence between -3105 and -3050 bp of the TAT gene. Multiple, clustered mutations of this sequence reduced, but did not eliminate, the negative activity. Further efforts to restrict the negative element were unsuccessful, suggesting that multiple sequences are required for full activity. High affinity, sequence-specific binding of a trans-acting factor(s) was observed in gel shift assays. This binding was half-maximally competed by a 4.4-fold excess of nonradioactive probe and was very stable once formed (Delta H double dagger(dissoc.) = 32 kcal/mol), suggesting that low concentrations of a high affinity binding protein(s) exist in nuclear extracts. Further support for this conclusion came from the observation that cotransfection of a plasmid containing multiple copies of the 56-bp negative element was able to relieve the negation of GME activity in a GME-56-bp-GRE reporter construct. These data directly support the role of a trans-acting factor(s) in binding to the 56-bp negative element and blocking GME activity. Collectively, these data suggest that glucocorticoid induction of TAT gene expression is subject to multiple levels of control by several new cis-acting elements and thus is much more complex than previously appreciated. C1 NIDDKD,STEROID HORMONES SECT,CELLULAR & MOLEC BIOL LAB,NIH,BETHESDA,MD 20892. NR 50 TC 22 Z9 21 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAY PY 1996 VL 10 IS 5 BP 463 EP 476 DI 10.1210/me.10.5.463 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UK448 UT WOS:A1996UK44800001 PM 8732678 ER PT J AU Chen, ZP Berkower, I Ching, WM Wang, RYH Alter, HJ Shih, JWK AF Chen, ZP Berkower, I Ching, WM Wang, RYH Alter, HJ Shih, JWK TI Identification of a murine CD4(+) T-lymphocyte response site in hepatitis C virus core protein SO MOLECULAR IMMUNOLOGY LA English DT Article DE HCV; truncated recombinant core proteins; immune responses; epitope mapping; H-2 congenic mice; T helper epitope ID NON-B-HEPATITIS; CHRONIC NON-A; POSTTRANSFUSION HEPATITIS; NUCLEOTIDE-SEQUENCE; IMMUNE-RESPONSE; ANTIGEN; INFECTION; ANTIBODY; CELLS; NUCLEOPROTEIN AB T cell response to a recombinant HCV truncated core protein (cp1-10) was measured in a proliferation assay. Based on a 10-fold greater response to this truncated core protein than to its shorter form (cp1-8), a predominant epitope was mapped to the carboxyl quarter of this sequence. This epitope was further mapped to a synthetic peptide corresponding to amino acids 121-140 of the core protein. The peptide was antigenic for T cells of all three H-2 types tested, H-2 r, b and d, and the proliferating T cells were CD4(+). Besides inducing specific proliferation in vitro, peptide aa121-140 can prime helper T cells in vivo. When boosted with core protein, mice primed with peptide produced 64-fold higher antibody titer than without priming in 1 week. The identification of a broadly immunogenic T cell helper epitope on core protein may be important for vaccine design against HCV. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,OFF VACCINE RES & REVIEW,IMMUNOREGULAT LAB,BETHESDA,MD 20852. USN,MED RES INST,DEPT INFECT DIS,BETHESDA,MD 20889. ARMED FORCES INST PATHOL,AMER REGISTRY PATHOL,WASHINGTON,DC 20306. NR 43 TC 4 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD MAY-JUN PY 1996 VL 33 IS 7-8 BP 703 EP 709 DI 10.1016/0161-5890(96)00010-7 PG 7 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA VA418 UT WOS:A1996VA41800014 PM 8760282 ER PT J AU Hill, SA AF Hill, SA TI Limited variation and maintenance of tight genetic linkage characterize heteroallelic pilE recombination following DNA transformation of Neisseria gonorrhoeae SO MOLECULAR MICROBIOLOGY LA English DT Article ID ANTIGENIC VARIATION; MENINGITIDIS; CONVERSION; PROTEIN; ORGANIZATION; CHROMOSOME; RESISTANCE; GONOCOCCI; EXCHANGE; BACTERIA AB Genetic recombination impacts on neisserial biology in two ways: (i) specific loci undergo rearrangement at high frequency leading to the formation of many different alleles; and (ii) Neisseria, being naturally competent for DNA transformation, provide a means to disseminate the novel alleles throughout a population. In this study pilE was used as a model system to examine heteroallelic recombination following DNA transformation. When gonococci were transformed with chromosomal donor DNA containing different pilE alleles, the majority of pilE recombinants arose through allelic replacement. Go-conversion analysis across pilE showed that in similar to 85-90% of recombination events encompassing pilE and an adjacent opa locus, linkage was maintained (i.e. similar to 10-15% of recombination events terminated within the similar to 1000 base pair pilE/opaE interval). In addition to those recombinants that arose through allelic replacement, a large pilus-minus subpopulation was also observed (similar to 10% of all recombinants), indicating that many recombination events did not yield recombinant pilEs that could be assembled into functional pill. PilE mosaics increased following transformation with plasmid donor DNAs carrying pilE with limited flanking-sequence homology, suggesting a potential role for flanking-sequence homologies in mosaic formation. Overall, the data support the view that horizontal transmission of chromosomal DNA between gonococci will favour the spread of intact alleles, as opposed to expanding the allelic repertoire through the formation of gene mosaics. RP Hill, SA (reprint author), NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,NIH,HAMILTON,MT 59840, USA. NR 35 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAY PY 1996 VL 20 IS 3 BP 507 EP 518 DI 10.1046/j.1365-2958.1996.5201047.x PG 12 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA UL579 UT WOS:A1996UL57900006 PM 8736530 ER PT J AU Freemerman, AJ Turner, AJ Birrer, MJ Szabo, E Valerie, K Grant, S AF Freemerman, AJ Turner, AJ Birrer, MJ Szabo, E Valerie, K Grant, S TI Role of c-jun in human myeloid leukemia cell apoptosis induced by pharmacological inhibitors of protein kinase C SO MOLECULAR PHARMACOLOGY LA English DT Article ID TRANSCRIPTION FACTOR AP-1; HL-60 CELLS; MONOCYTIC DIFFERENTIATION; POTENTIAL INVOLVEMENT; EXPRESSION; ACTIVATION; ONCOGENE; DNA; PROTOONCOGENE; FOS AB Recent study results suggest that protein kinase C [PKC (EC 3.1.4.3)]-dependent up-regulation of c-jun may be involved in leukemic cell programmed cell death, or apoptosis, occurring in response to various chemotherapeutic agents. The current study was undertaken to further evaluate the contribution of c-jun in apoptosis with the use of two highly specific pharmacological inhibitors of PKC (calphostin C and chelerythrine). To address this issue, two human leukemic cell lines, HL-60 and U937, and a U937 subline stably expressing a dominant negative c-jun mutant (TAM67) were exposed to calphostin C and chelerythrine, and c-jun expression was monitored at both the mRNA and protein levels. Both PKC inhibitors induced the classic morphological features of apoptosis as well as internucleosomal DNA degradation in a concentration- and schedule-dependent manner. Concomitant with these changes, unequivocal increases were observed in c-jun mRNA (U937 and HL-60) and protein (U937). In contrast, up-regulation of c-jun mRNA and protein in TAM67-expressing cells exposed to both PKC inhibitors was markedly attenuated relative to effects observed in parental U937 cells. Importantly, despite impaired up-regulation of c-jun at both the message and protein levels, TAM67-expressing cells were equally susceptible to PKC inhibitor-induced apoptosis as parental and empty vector U937 cells. Collectively, these findings raise the possibility that c-jun up-regulation in human myeloid leukemia cells undergoing PKC inhibitor-associated apoptosis represents a response to, rather than a cause of, apoptotic events. They further suggest that this phenomenon involves pathways that do not require PKC activation. C1 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT MED,DIV HEMATOL & ONCOL,RICHMOND,VA 23298. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT RADIAT ONCOL,RICHMOND,VA 23298. NATL CANC INST,PREVENT RES BRANCH,NIH,ROCKVILLE,MD 20850. FU NCI NIH HHS [CA16059, CA63753-01, CA09564-05] NR 49 TC 35 Z9 35 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAY PY 1996 VL 49 IS 5 BP 788 EP 795 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UK004 UT WOS:A1996UK00400005 PM 8622627 ER PT J AU Nerurkar, PV Schut, HAJ Anderson, LM Riggs, CW Fornwald, LW Davis, CD Snyderwine, EG Thorgeirsson, SS Weber, WW Rice, JM Levy, GN AF Nerurkar, PV Schut, HAJ Anderson, LM Riggs, CW Fornwald, LW Davis, CD Snyderwine, EG Thorgeirsson, SS Weber, WW Rice, JM Levy, GN TI Ahr locus phenotype in congenic mice influences hepatic and pulmonary DNA adduct levels of 2-amino-3-methylimidazo[4,5-f]quinoline in the absence of cytochrome P450 induction SO MOLECULAR PHARMACOLOGY LA English DT Article ID METABOLIC-ACTIVATION; HETEROCYCLIC AMINES; MUTAGENIC ACTIVATION; N-ACETYLTRANSFERASE; AROMATIC-AMINES; CDF1 MICE; IQ; RATS; MOUSE; CARCINOGENICITY AB The potent food mutagen/carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) undergoes metabolic N-hydroxylation by cytochromes P450, including cytochrome P450 1A2, followed by generation of an unstable ester catalyzed by acetyltransferases; promutagenic DNA adducts result. Genetic polymorphisms in these enzymes have been implicated in human cancer risk related to arylamine exposure. We investigated the effects of Ahr locus and acetylator polymorphisms on P-32-postlabeled IQ/DNA adducts in lungs and livers of female C57BL/6 mice congenic for slow acetylation and/or Ahr-nonresponsiveness; some groups were pretreated with beta-naphthoflavone (beta NF), a cytochrome P450 1A inducer. Total adducts in lung were doubled by beta NF pretreatment in Ahr-responsive mice only and consisted of less than or equal to 30% adduct 2 and less than or equal to 60% adduct 3. In contrast, in Ahr-nonresponsive mice, adducts 2 and 3 were each less than or equal to 7% of the total. Livers of noninduced Ahr-responsive mice formed 6-18-fold more adducts than those of nonresponsive mice. This striking difference was not due to altered levels of cyp1a-2, as indicated by specific enzyme assays and immunoblotting, and was not accompanied by a comparable increase in the ability of liver preparations to activate IQ to a mutagen in the Ames test. Pretreatment of responsive mice with beta NF to induce cyp1a-1 and cyp1a-2 led to a reduction in liver adduct levels. Acetylation phenotype also had a significant effect in Ahr-responsive mice, with 3-fold more adducts in slow than in rapid acetylators. These results indicate that in uninduced mice, the normal Ah receptor facilitates formation of IQ/DNA adducts in liver and alters the profile of adducts in lung, via an unknown mechanism, whereas the Ah receptor-dependent enzyme induction reduces adducts in liver, probably due to increased detoxification, but increases them in lung. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. MED COLL OHIO,DEPT PATHOL,TOLEDO,OH 43699. NCI,FREDERICK CANC RES & DEV CTR,DATA MANAGEMENT SERV,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC INC,FREDERICK,MD 21702. NCI,EXPTL CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. UNIV MICHIGAN,DEPT PHARMACOL,ANN ARBOR,MI 48109. NR 40 TC 12 Z9 12 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAY PY 1996 VL 49 IS 5 BP 874 EP 881 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UK004 UT WOS:A1996UK00400015 PM 8622637 ER PT J AU Song, ZH Bonner, TI AF Song, ZH Bonner, TI TI A lysine residue of the cannabinoid receptor is critical for receptor recognition by several agonists but not WIN55212-2 SO MOLECULAR PHARMACOLOGY LA English DT Article ID BINDING; ANALOGS; INHIBITION; BRAIN; CELLS; DNA AB Lys(192) in the third transmembrane domain of the human CB1 cannabinoid receptor was converted to an alanine to study its role in receptor recognition and activation by agonists. HU-210, CP-55940, WIN55212-2, and anandamide, four cannabinoid agonists with distinct chemical structures, were used to characterize the wild-type and the mutant receptors. In human embryonal kidney 293 cells stably expressing the wild-type receptor, specific binding to [H-3]WIN55212-2 and inhibition of cAMP accumulation by cannabinoid agonists were demonstrated, with different ligands exhibiting the expected rank orders of potency and stereoselectivity in competition binding and functional assays. In cells expressing the mutant receptor, the binding affinity of the receptor for [H-3]WIN55212-2 was only slightly affected (the K-d for the mutant receptor was twice that of the wild-type), and the ability of WIN55212-2 to inhibit cAMP accumulation was unchanged. However, HU-210, CP-55940, and anandamide were unable to compete for [H-3]WIN55212-2 binding to the mutant receptor. In addition, the potencies of HU-210, CP-55940, and anandamide in inhibiting cAMP accumulation were reduced by >100-fold. These results demonstrate that Lys(192) is critical for receptor binding by HU-210, CP-55940, and anandamide. Because Lys(192) is not important for receptor binding and activation by WIN55212-2, WIN55212-2 must interact with the cannabinoid receptor through at least one point of interaction that is distinct from those of the three other agonists. RP Song, ZH (reprint author), NIMH,CELL BIOL LAB,NIH,BLDG 36,ROOM 3A-17,BETHESDA,MD 20892, USA. NR 32 TC 180 Z9 191 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAY PY 1996 VL 49 IS 5 BP 891 EP 896 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UK004 UT WOS:A1996UK00400017 PM 8622639 ER PT J AU Tooley, PW Garfinkel, DJ AF Tooley, PW Garfinkel, DJ TI Presence of Ty1-copia group retrotransposon sequences in the potato late blight pathogen Phytophthora infestans SO MOLECULAR PLANT-MICROBE INTERACTIONS LA English DT Article DE potato late blight; transposable element ID PLANTS; RETROELEMENTS; EVOLUTION AB Multiple copies of retrotransposon reverse transcriptase coding sequences were identified in Phytophthora infestans by polymerase chain reaction (PCR) amplification using degenerate primers, The I! infestans sequences belong to the Ty1-copia superfamily, and putative elements from different P. infestans isolates show restriction site polymorphisms, Some contain complete open reading frames while others do not, indicating the presence of potentially active as well as inactive elements. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,GENE REGULAT & CHORMOSOME BIOL LAB,FREDERICK,MD 21702. RP Tooley, PW (reprint author), USDA ARS,FT DETRICK,MD 21701, USA. FU NCI NIH HHS [N01-CO-46000] NR 25 TC 17 Z9 17 U1 0 U2 0 PU AMER PHYTOPATHOLOGICAL SOC PI ST PAUL PA 3340 PILOT KNOB ROAD, ST PAUL, MN 55121 SN 0894-0282 J9 MOL PLANT MICROBE IN JI Mol. Plant-Microbe Interact. PD MAY PY 1996 VL 9 IS 4 BP 305 EP 309 DI 10.1094/MPMI-9-0305 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Plant Sciences SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Plant Sciences GA UJ023 UT WOS:A1996UJ02300011 PM 8634480 ER PT J AU Licinio, J AF Licinio, J TI The dopamine D4 receptor and attention deficit hyperactivity disorder SO MOLECULAR PSYCHIATRY LA English DT Editorial Material RP Licinio, J (reprint author), NIMH,NIH,UNIT CLIN RES,CLIN NEUROENDOCRINOL BRANCH,INTRAMURAL RES PROGRA,BLDG 10,RM 3S231,BETHESDA,MD 20892, USA. RI Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 9 TC 2 Z9 2 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAY PY 1996 VL 1 IS 2 BP 83 EP 84 PG 2 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA VG815 UT WOS:A1996VG81500001 PM 9118326 ER PT J AU Accili, D Fuchs, S AF Accili, D Fuchs, S TI A new look at dopamine D3 receptors SO MOLECULAR PSYCHIATRY LA English DT Article C1 WEIZMANN INST SCI,DEPT CHEM IMMUNOL,IL-76100 REHOVOT,ISRAEL. RP Accili, D (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892, USA. NR 4 TC 3 Z9 3 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAY PY 1996 VL 1 IS 2 BP 93 EP 94 PG 2 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA VG815 UT WOS:A1996VG81500004 PM 9118329 ER PT J AU Goldstein, DS AF Goldstein, DS TI The sympathetic nervous system and the 'fight-or-flight' response: Outmoded ideas? SO MOLECULAR PSYCHIATRY LA English DT Article ID PLASMA-CATECHOLAMINE; BEHAVIOR; STRESS; RATS RP Goldstein, DS (reprint author), NINCDS,CLIN NEUROSCI BRANCH,NIH,10-6N252 9000 ROCKVILLE PIKE,10 CTR DR MSC-1424,BETHESDA,MD 20892, USA. NR 20 TC 6 Z9 7 U1 2 U2 6 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAY PY 1996 VL 1 IS 2 BP 95 EP 97 PG 3 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA VG815 UT WOS:A1996VG81500005 PM 9118330 ER PT J AU Wong, ML Xin, WW Duman, RS AF Wong, ML Xin, WW Duman, RS TI Rat LCR1: Cloning and cellular distribution of a putative chemokine receptor in brain SO MOLECULAR PSYCHIATRY LA English DT Article DE brain; nucleic acid hybridization; chemokine receptor; cytokine; cytokine receptor; GenBank accession number U54791 ID HUMAN INTERLEUKIN-8 RECEPTOR; MOLECULAR-CLONING; NEUROPEPTIDE-Y; FUNCTIONAL EXPRESSION; CDNA; PROTEIN; LOCALIZATION; CELLS AB We report here the isolation and localization of RLCR1, a rat G-protein-coupled receptor, which is the homologue (94% amino acid identity) of the bovine receptor (LCR1) isolated from a locus coeruleus cDNA library. The deduced amino acid sequence of the RLCR1 encodes a protein of 347 amino acids and yields a hydropathicity profile characteristic of receptors with seven putative transmembrane regions. The structure of the receptor protein encoded by RLCR1 is most similar to that of the Burkitt's lymphoma receptor 2 (43% identical) and C-C chemokine receptor type 1 (38%). The mRNA corresponding to the cDNA was detected in various rat tissues including spleen, liver, heart, and brain. In situ hybridization analysis shows that RLCR1 is distributed both in neurons and glia in the adult rat brain. Levels of RLCR1 mRNA are highest in the ependymal layer as previously reported. In addition, we found that RLCR1 is also expressed at lower levels in cerebral cortex, hippocampus, cerebellum, and brainstem. The finding that LCR1 is expressed in the adult indicates that this receptor influences neuronal function at times after maturation of the brain. C1 BOSTON UNIV,CTR HUMAN GENET,DNA DIAGNOST LAB,BOSTON,MA 02118. YALE UNIV,SCH MED,DIV MOL PSYCHIAT,DEPT PSYCHIAT,NEW HAVEN,CT 06511. RP Wong, ML (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,NIH,BLDG 10 ROOM 3S231,BETHESDA,MD 20892, USA. RI Wong, Ma-Li/D-7903-2011 FU NIDA NIH HHS [DA08227]; NIMH NIH HHS [MH44694] NR 24 TC 39 Z9 39 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAY PY 1996 VL 1 IS 2 BP 133 EP 140 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA VG815 UT WOS:A1996VG81500011 PM 9118323 ER PT J AU Mori, C Nakamura, N Welch, JE Shiota, K Eddy, EM AF Mori, C Nakamura, N Welch, JE Shiota, K Eddy, EM TI Testis-specific expression of mRNAs for a unique human type 1 hexokinase lacking the porin-binding domain SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Article DE hexokinase; human; testis; gene expression; spermatogenesis ID AMINO-ACID-SEQUENCE; MESSENGER-RIBONUCLEIC-ACID; MOUSE SPERMATOGENIC CELLS; CLONED CDNA; MAMMALIAN HEXOKINASE; RAT HEXOKINASE; GENE; KINASE; GLUCOKINASE; MEMBRANE AB Several enzymes in the glycolytic pathway are reported to have spermatogenic cell-specific isozymes. We reported recently the cloning of cDNAs representing three unique type 1 hexokinase mRNAs (mHk1-sa, mHk1-sb, and mHk1-sc) present only in mouse spermatogenic cells and the patterns of expression of these mRNAs (Mori et al., 1993: Biol Reprod 49:191-203). The mRNAs contain a spermatogenic cell-specific sequence, but lack the sequence for the porin-binding domain that somatic cell hexokinases use to bind to a pore-forming protein in the outer mitochondrial membrane. We now report the cloning of cDNAs representing three unique human type 1 hexokinase mRNAs (hHK1-ta, hHK1-tb, and hHK1-tc) expressed in testis, but not detected by Northern analysis in other human tissues. These mRNAs also contain a testis-specific sequence not present in somatic cell type 1 hexokinase, but lack the sequence for the porin-binding domain. The hHK1-tb and hHK1-tc mRNAs each contain an additional unique sequence. The testis-specific sequence of the human mRNAs is similar to the spermatogenic cell-specific sequence of the mouse mRNAs. Furthermore, Northern analysis of RNA from mouse, hamster, guinea pig, rabbit, ram, human, and rat demonstrated expression of type 1 hexokinase mRNAs lacking the porin-binding domain in the testes of these mammals. These results suggest that hexokinase may have unique structural or functional features in spermatogenic cells and support a model proposed by others for hexokinase gene evolution in mammals. (C) 1996 Wiley-Liss, Inc. C1 NATL INST ENVIRONM HLTH SCI,NATL INST HLTH,REPROD & DEV TOXICOL LAB,GAMETE BIOL SECT,RES TRIANGLE PK,NC. US EPA,NATL HLTH & ENVIRONM EFFECT RES LAB,DIV DEV TOXICOL,REPROD TOXICOL BRANCH,RES TRIANGLE PK,NC 27711. RP Mori, C (reprint author), KYOTO UNIV,FAC MED,DEPT ANAT,SAKYO KU,KYOTO 60601,JAPAN. NR 32 TC 18 Z9 18 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1040-452X J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD MAY PY 1996 VL 44 IS 1 BP 14 EP 22 DI 10.1002/(SICI)1098-2795(199605)44:1<14::AID-MRD2>3.0.CO;2-W PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA UH521 UT WOS:A1996UH52100002 PM 8722688 ER PT J AU Metman, LV Blanchet, PJ deJong, D Mouradian, MM Chase, TN AF Metman, LV Blanchet, PJ deJong, D Mouradian, MM Chase, TN TI Effect of the putative dopamine D-1 agonist and D-2 antagonist FCE 23884 on Parkinson's disease SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; dyskinesias; FCE 23884; D-1 agonist; D-2 antagonist ID SUBSTRATE-DEPENDENT INTERACTION; RECEPTOR SUPERSENSITIVITY; ANTIPARKINSONIAN ACTIVITY; MACACA-FASCICULARIS; REVEAL DOPAMINE-D2; ADENYLYL-CYCLASE; ANIMAL-MODELS; MPTP; MONKEY; SYSTEM AB The ergoline derivative FCE 23884 acts as a dopamine D-1 agonist in untreated parkinsonian animals and as a D-2 antagonist in animals whose dopamine system is intact or levodopa treated. To evaluate whether this dual action might benefit patients with Parkinson's disease (PD) who have developed levodopa-induced dyskinesias, the motor effects of FCE 23884 were examined in seven such individuals using a double-blind, placebo-controlled design. At doses up to the maximum tolerated dose (3.5 +/- 0.5 mg), FCE 23884 monotherapy did not affect parkinsonian severity. On the other hand, coadministration of FCE 23884 with a mildly dyskinetic dose of levodopa, infused intravenously under steady-state conditions, reduced the antiparkinson response by 54 +/- 19% and tended to diminish dyskinesia severity. The results thus fail to suggest any useful role for FCE 23884 in the symptomatic treatment of PD. Although D-2 receptor blockade provided by FCE 23884 antagonizes both the antiparkinson and dyskinesigenic responses to levodopa, the degree of D-1 receptor stimulation appears insufficient to ameliorate parkinsonian symptomatology. C1 NINCDS,EXPTL THERAPEUT BRANCH,NIH,BETHESDA,MD 20892. OI Mouradian, M. Maral/0000-0002-9937-412X NR 21 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAY PY 1996 VL 11 IS 3 BP 257 EP 260 DI 10.1002/mds.870110307 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA UH161 UT WOS:A1996UH16100006 PM 8723141 ER PT J AU Sikorski, RS Peters, R AF Sikorski, RS Peters, R TI Cell and tissue culture on the web SO NATURE BIOTECHNOLOGY LA English DT Editorial Material C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Sikorski, RS (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAY PY 1996 VL 14 IS 5 BP 656 EP 656 DI 10.1038/nbt0596-656a PG 1 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA UL604 UT WOS:A1996UL60400036 PM 9630962 ER PT J AU Kaler, SG AF Kaler, SG TI Menkes disease mutations and response to early copper histidine treatment SO NATURE GENETICS LA English DT Letter ID MESSENGER-RNAS C1 CHILDRENS HOSP,WASHINGTON,DC. RP Kaler, SG (reprint author), NINCDS,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892, USA. NR 8 TC 44 Z9 44 U1 0 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 1996 VL 13 IS 1 BP 21 EP 22 DI 10.1038/ng0596-21 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA UH430 UT WOS:A1996UH43000010 PM 8673098 ER PT J AU Poetter, K Jiang, H Hassanzadeh, S Master, SR Chang, A Dalakas, MC Rayment, I Sellers, JR Fananapazir, L Epstein, ND AF Poetter, K Jiang, H Hassanzadeh, S Master, SR Chang, A Dalakas, MC Rayment, I Sellers, JR Fananapazir, L Epstein, ND TI Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle SO NATURE GENETICS LA English DT Article ID HYPERTROPHIC CARDIOMYOPATHY; BETA-MYOSIN; HEAVY-CHAIN; STRETCH ACTIVATION; GENE; EXPRESSION; PHOSPHORYLATION; SEQUENCE; LOCATION; ACTIN AB The muscle myosins are hexomeric proteins consisting of two heavy chains and two pairs of light chains, the latter called essential (ELC) and regulatory (RLC). The light chains stabilize the long alpha helical neck of the myosin head. Their function in striated muscle, however, is only partially understood. We report here the identification of distinct missense mutations in a skeletal/ventricular ELC and RLC, each of which are associated with a rare variant of cardiac hypertrophy as well as abnormal skeletal muscle. We show that myosin containing the mutant ELC has abnormal function, map the mutant residues on the three-dimensional structure of myosin and suggest that the mutations disrupt the stretch activation response of the cardiac papillary muscles. C1 NHLBI,INHERITED CARDIAC DIS SECT,NIH,BETHESDA,MD 20892. NHLBI,MOLEC CARDIOL LAB,NIH,BETHESDA,MD 20892. NINCDS,NEUROMUSCULAR DIS SECT,NIH,BETHESDA,MD 20892. UNIV WISCONSIN,INST ENZYME RES,MADISON,WI 53705. UNIV WISCONSIN,DEPT BIOCHEM,MADISON,WI 53705. OI rayment, ivan/0000-0001-9279-7835 NR 45 TC 392 Z9 409 U1 1 U2 4 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 1996 VL 13 IS 1 BP 63 EP 69 DI 10.1038/ng0596-63 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA UH430 UT WOS:A1996UH43000017 PM 8673105 ER PT J AU Nelen, MR Padberg, GW Peeters, EAJ Lin, AY vandenHelm, B Frants, RR Coulon, V Goldstein, AM vanReen, MMM Easton, DF Eeles, RA Hodgson, S Mulvihill, JJ Murday, VA Tucker, MA Mariman, ECM Starink, TM Ponder, BAJ Ropers, HH Kremer, H Longy, M Eng, C AF Nelen, MR Padberg, GW Peeters, EAJ Lin, AY vandenHelm, B Frants, RR Coulon, V Goldstein, AM vanReen, MMM Easton, DF Eeles, RA Hodgson, S Mulvihill, JJ Murday, VA Tucker, MA Mariman, ECM Starink, TM Ponder, BAJ Ropers, HH Kremer, H Longy, M Eng, C TI Localization of the gene for Cowden disease to chromosome 10q22-23 SO NATURE GENETICS LA English DT Letter ID KRUPPEL; DROSOPHILA; REPRESSION; DNA C1 UNIV NIJMEGEN HOSP,DEPT NEUROL,6500 HB NIJMEGEN,NETHERLANDS. LEIDEN UNIV,DEPT NEUROL,LEIDEN,NETHERLANDS. NCI,NIH,ROCKVILLE,MD. UNIV NIJMEGEN HOSP,DEPT HUMAN GENET,6500 HB NIJMEGEN,NETHERLANDS. LEIDEN UNIV,DEPT HUMAN GENET,MGC,2300 RA LEIDEN,NETHERLANDS. INST BERGONIE,BORDEAUX,FRANCE. INST PUBL HLTH,CRC,GENET EPIDEMIOL RES GRP,CAMBRIDGE,ENGLAND. ROYAL MARSDEN HOSP,INST CANC RES,SUTTON,SURREY,ENGLAND. GUYS & ST THOMAS HOSP,DEPT CLIN GENET,LONDON SE1 9RT,ENGLAND. UNIV PITTSBURGH,DEPT HUMAN GENET,PITTSBURGH,PA. ST GEORGE HOSP,DEPT CLIN GENET,LONDON,ENGLAND. NCI,GENET EPIDEMIOL BRANCH,ROCKVILLE,MD. FREE UNIV AMSTERDAM HOSP,DEPT DERMATOL,1081 HV AMSTERDAM,NETHERLANDS. UNIV CAMBRIDGE,CRC,HUMAN CANC GENET RES GRP,CAMBRIDGE,ENGLAND. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. RI Kremer, Hannie/F-5126-2010; Padberg, G.W.A.M./H-8079-2014; Tucker, Margaret/B-4297-2015; Nelen, Marcel/L-4542-2015; Reen, M.M.M./L-4593-2015; OI Kremer, Hannie/0000-0002-0841-8693; Eng, Charis/0000-0002-3693-5145 NR 29 TC 382 Z9 385 U1 3 U2 8 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 1996 VL 13 IS 1 BP 114 EP 116 DI 10.1038/ng0596-114 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA UH430 UT WOS:A1996UH43000028 PM 8673088 ER PT J AU Phelan, CM Lancaster, JM Tonin, P Gumbs, C Cochran, C Carter, R Ghadirian, P Perret, C Moslehi, R Dion, F Faucher, MC Dole, K Karimi, S Foulkes, W Lounis, H Warner, E Goss, P Anderson, D Larsson, C Narod, SA Futreal, PA AF Phelan, CM Lancaster, JM Tonin, P Gumbs, C Cochran, C Carter, R Ghadirian, P Perret, C Moslehi, R Dion, F Faucher, MC Dole, K Karimi, S Foulkes, W Lounis, H Warner, E Goss, P Anderson, D Larsson, C Narod, SA Futreal, PA TI Mutation analysis of the BRCA2 gene in 49 site-specific breast cancer families SO NATURE GENETICS LA English DT Letter C1 DUKE UNIV,MED CTR,DEPT SURG,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT GENET,DURHAM,NC 27710. DUKE UNIV,MED CTR,DIV GYNECOL ONCOL,DURHAM,NC 27710. MCGILL UNIV,DEPT HUMAN GENET,MONTREAL,PQ,CANADA. MCGILL UNIV,DEPT MED,MONTREAL,PQ,CANADA. MONTREAL GEN HOSP,RES INST,MONTREAL,PQ H3G 1A4,CANADA. KAROLINSKA HOSP,DEPT MOLEC MED,ENDOCRINE TUMOUR UNIT,STOCKHOLM,SWEDEN. NIEHS,RES TRIANGLE PK,NC 27709. MCMASTER UNIV,MED CTR,HAMILTON,ON,CANADA. HOP HOTEL DIEU,RES CTR,EPIDEMIOL RES UNIT,MONTREAL,PQ,CANADA. UNIV BRITISH COLUMBIA,DEPT MED GENET,VANCOUVER,BC,CANADA. UNIV MONTREAL,INST CANC MONTREAL,CTR LOUIS CHARLES SIMARD,MONTREAL,PQ H2L 4M1,CANADA. SUNNYBROOK REG CANC CTR,TORONTO,ON,CANADA. TORONTO HOSP,TORONTO,ON M5T 2S8,CANADA. PRINCESS MARGARET HOSP,TORONTO,ON M4X 1K9,CANADA. MD ANDERSON HOSP & TUMOR INST,HOUSTON,TX. WOMENS COLL HOSP,TORONTO,ON M5S 1B2,CANADA. FU NCI NIH HHS [P50-CA68438, R21-CA66228] NR 10 TC 212 Z9 212 U1 0 U2 3 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 1996 VL 13 IS 1 BP 120 EP 122 DI 10.1038/ng0596-120 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA UH430 UT WOS:A1996UH43000030 PM 8673090 ER PT J AU Wong, ML Rettori, V AlShekhlee, A Bongiorno, PB Canteros, G McCann, SM Gold, PW Licinio, J AF Wong, ML Rettori, V AlShekhlee, A Bongiorno, PB Canteros, G McCann, SM Gold, PW Licinio, J TI Inducible nitric oxide synthase gene expression in the brain during systemic inflammation SO NATURE MEDICINE LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; ULCERATIVE-COLITIS; RESPONSE SYNDROME; ENCEPHALOPATHY; NEUROTOXICITY; MECHANISMS; CULTURES; DISEASE; NITRATE AB Inducible nitric oxide synthase (iNOS) is a transcriptionally regulated enzyme that synthesizes nitric oxide from L-arginine(1) that has a key role in the pathophysiology of systemic inflammation and sepsis. Transgenic animals with a null mutation for the iNOS gene are resistant to hypotension and death caused by Escherichia coli lipopolysaccharide (LPS)(2,3). The regulation of peripheral iNOS has been well studied in sepsis, but little is known about iNOS regulation in the brain during systemic inflammation or sepsis. We show that at baseline there is no detectable iNOS gene expression in the brain, but a detailed neuroanatomical study reveals that early in the course of systemic inflammation there is a profound induction of iNOS messenger RNA in vascular, glial and neuronal structures of the rat brain, accompanied by the production of nitric oxide (NO) metabolites in brain parenchyma and cerebrospinal fluid (CSF). We propose that the spillover of nitrite into the CSF has the potential to be a diagnostic marker for systemic inflammation and sepsis. Pharmacological interventions aimed at regulating iNOS function in the brain might represent a new treatment strategy in sepsis. Brain iNOS may be relevant to the pathophysiology, diagnosis and treatment of systemic inflammation and sepsis. C1 NIMH,NIH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. CONSEJO NACL INVEST CIENT & TECN,CENTRO ESTUDIOS FARMACOLOG & BOTANICOS,BUENOS AIRES,DF,ARGENTINA. LOUISIANA STATE UNIV,PENNINGTON BIOMED RES CTR,BATON ROUGE,LA 70808. RI Wong, Ma-Li/D-7903-2011; Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 34 TC 221 Z9 224 U1 0 U2 3 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 1996 VL 2 IS 5 BP 581 EP 584 DI 10.1038/nm0596-581 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA UJ230 UT WOS:A1996UJ23000044 PM 8616720 ER PT J AU Abraham, EH Vos, P Kahn, J Grubman, SA Jefferson, DM Ding, I Okunieff, P AF Abraham, EH Vos, P Kahn, J Grubman, SA Jefferson, DM Ding, I Okunieff, P TI Cystic fibrosis hetero- and homozygosity is associated with inhibition of breast cancer growth SO NATURE MEDICINE LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; ANTICANCER ACTIVITIES; ADENINE-NUCLEOTIDES; ANIMAL-MODEL; GENE; CELLS; MICE AB Cystic fibrosis (CF) is the most common lethal recessive genetic disease of the Caucasian population. Although reports of cancer frequency in CF have emphasized an elevated observed-to-expected ratio of 6.5 for digestive tract cancers, these studies also show a significantly decreased observed-to-expected ratio for other malignancies including breast cancer. The cystic fibrosis transmembrane conductance regulator (CFTR) functions as an ATP channel(1-3). We found that heterozygous and homozygous CFTR knockout mice had elevated blood ATP concentrations. Elevated extracellular ATP is known to inhibit tumor growth in vivo and in vitro(4-7). Using double mutant mice created by F-2 generation crosses of CFTR knockout and nude mice, we observed reduced breast tumor implantability in CFTR homozygous nude animals. Decreased tumor growth rate was observed in both CFTR heterozygous and homozygous nude animals. Extracellular ATP reduced human tumor cell growth rate in vitro, and a breast transfected with human CFTR that had high extracellular ATP concentrations in vitro correspondingly had a slower growth rate in vivo. The results suggest that both CFTR heterozygosity and homozygosity suppress breast cancer growth and that elevated extracellular ATP can account for this phenomenon. C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. TUFTS UNIV,NEW ENGLAND MED CTR,DEPT PHYSIOL & PEDIAT,BOSTON,MA 02111. RP Abraham, EH (reprint author), NCI,RADIAT ONCOL BRANCH,BLDG 10,ROOM B3B69,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 22 TC 42 Z9 42 U1 1 U2 1 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 1996 VL 2 IS 5 BP 593 EP 596 DI 10.1038/nm0596-593 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA UJ230 UT WOS:A1996UJ23000047 PM 8616723 ER PT J AU Troncoso, JC Martin, LJ DalForno, G Kawas, CH AF Troncoso, JC Martin, LJ DalForno, G Kawas, CH TI Neuropathology in controls and demented subjects from the Baltimore Longitudinal Study of Aging SO NEUROBIOLOGY OF AGING LA English DT Article DE aging; Alzheimer's disease; beta-amyloid protein; senile plaques ID ALZHEIMERS-DISEASE CERAD; NEUROFIBRILLARY TANGLES; CONSORTIUM; DIAGNOSIS; ESTABLISH; REGISTRY; PLAQUES; PROTEIN; BRAINS; OLDER AB To establish correlations among cognitive states and neuropathology, we have examined 22 subjects (69-97 years of age) from the Baltimore Longitudinal Study of Aging (BLSA), of whom 15 had normal and stable cognitive performances and seven had dementia of variable severity. In the majority of normal subjects, few or no beta-amyloid (A beta) deposits or senile plaques (SP) were present in the neocortex, but neurofibrillary tangles (NFT) were consistently found in CA1 of hippocampus and layer II of entorhinal cortex. In two (15%) normal individuals, the densities of SP were consistent with the diagnosis of possible Alzheimer's disease (AD). We speculate that these cases with normal cognitive states and abundant neocortical SP may represent preclinical AD. We conclude that the neocortex of a majority of cognitively intact individuals can remain free of A beta deposits or SP, even into the tenth decade of life. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,NIA,CTR GERONTOL RES,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,ALZHEIMERS DIS RES CTR,BALTIMORE,MD 21205. RP Troncoso, JC (reprint author), JOHNS HOPKINS UNIV,SCH MED,NEUROPATHOL LAB,558 ROSS RES BLDG,720 RUTLAND AVE,BALTIMORE,MD 21205, USA. FU NIA NIH HHS [AG 05146, AG 07914, AG 08325] NR 44 TC 106 Z9 107 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAY-JUN PY 1996 VL 17 IS 3 BP 365 EP 371 DI 10.1016/0197-4580(96)00028-0 PG 7 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA UN895 UT WOS:A1996UN89500006 PM 8725897 ER PT J AU Kusztos, RD Ingram, DK Spangler, EL London, ED AF Kusztos, RD Ingram, DK Spangler, EL London, ED TI Effects of aging and chronic nimodipine on hippocampal binding of [H-3]CGS 19755 SO NEUROBIOLOGY OF AGING LA English DT Article DE NMDA receptor; calcium channels; nimodipine; aging; learning; memory; hippocampus ID METHYL-D-ASPARTATE; LONG-TERM POTENTIATION; ALZHEIMERS-DISEASE; TCP BINDING; NMDA RECEPTORS; AGED RATS; DENSITY; BRAIN; SENSITIVITY; IMPAIRMENT AB Previous studies have suggested that aging is associated with impaired behavioral performance and with decrements of N-methyl-D-aspartate (NMDA) receptors in the rat hippocampus. Other studies have indicated that chronic treatment with nimodipine, a Ca2+ channel antagonist, prevents the age-related decline in performance by rats in behavioral tasks. Therefore, we tested whether nimodipine altered binding of [H-3]CGS 19755 to hippocampal NMDA receptors in rats whose performance on a 14-unit T maze had been tested previously (14). No significant age difference was observed in [H-3]CGS 19755 binding in hippocampi from old Fischer-344 rats (27 months) as compared with mature but nor senescent rats (9 months). however, old rats that received chronic treatment with a low dose of nimodipine (20 mg pellets implanted subcutaneously twice during 70 days of treatment) showed higher levels of binding. A high dose of nimodipine (40 mg pellets implanted by the same route and at the same rimes as the low dose) was without effect on [H-3]CGS 19755 binding, although aged rats given this treatment performed better in the maze than rats that received no nimodipine or the low dose. In a second experiment comparing hippocampi of young (4 months) and old (24 months) rats, saturation studies confirmed the lack of an age difference in [H-3]CGS 19755 binding. The findings suggest that neither the age-related decline in maze performance nor the enhancement of behavior by nimodipine depend upon changes in hippocampal NMDA receptors. C1 NIDA, NEUROIMAGING & DRUG ACT SECT,NEUROSCI BRANCH, INTRAMURAL RES PROGRAM,NIH, BALTIMORE, MD 21224 USA. NIA, MOLEC PHYSIOL & GENET SECT, NATHAN W SHOCK LABS, GERONTOL RES CTR, BALTIMORE, MD 21224 USA. JOHNS HOPKINS SCH MED, DEPT RADIOL, BALTIMORE, MD 21204 USA. UNIV MARYLAND, SCH MED, DEPT PHARMACOL & EXPTL THERAPEUT, BALTIMORE, MD 21201 USA. NR 36 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAY-JUN PY 1996 VL 17 IS 3 BP 453 EP 457 DI 10.1016/0197-4580(96)00032-2 PG 5 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA UN895 UT WOS:A1996UN89500016 PM 8725907 ER PT J AU Ingram, DK AF Ingram, DK TI Brain-behavior linkages in aged rodent models: Strategies for examining individual differences - Comment SO NEUROBIOLOGY OF AGING LA English DT Article ID RADIAL MAZE PERFORMANCE; MOTOR-PERFORMANCE; RATS; MICE; IMPAIRMENT; VALIDITY; MEMORY; YOUNG RP Ingram, DK (reprint author), NIA,GERONTOL RES CTR,MOLEC PHYSIOL & GENET SECT,NATHAN W SHOCK LABS,NATL INST HLTH,BALTIMORE,MD 21224, USA. NR 26 TC 12 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAY-JUN PY 1996 VL 17 IS 3 BP 497 EP 499 DI 10.1016/0197-4580(96)00003-6 PG 3 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA UN895 UT WOS:A1996UN89500026 PM 8725916 ER PT J AU Veeranna Shetty, KT Amin, N Grant, P Albers, RW Pant, HC AF Veeranna Shetty, KT Amin, N Grant, P Albers, RW Pant, HC TI Inhibition of neuronal cyclin-dependent kinase-5 by staurosporine and purine analogs is independent of activation by munc-18 SO NEUROCHEMICAL RESEARCH LA English DT Article DE cdk5; staurosporine; phosphorylation; p67 (Munc-18); neurofilament ID NERVE GROWTH-FACTOR; DIRECTED PROTEIN-KINASE; POTENT INHIBITOR; PHEOCHROMOCYTOMA CELLS; PHOSPHORYLATION; DIFFERENTIATION; ESTABLISHMENT; PLATELETS; P34CDC2; UCN-01 AB Neuronal cdk5 can phosphorylate certain lys-ser-pro (KSP) motifs of neurofilaments and tau protein in the nervous system. We have immunoprecipitated the cdk5 from rat brain using a polyclonal antibody raised against the C-terminus of cdk5. The immunoprecipitate has phosphorylated a KSPXK peptide analog of NF-H, as well as histone H1 and a bacterially expressed rat NF-H protein. The kinase activity was inhibited by staurosporine, isopentanyladenine and olomoucine in a dose dependent manner. Kinetic studies indicated Ki values of 39 nM, 38 mu M and 8 mu M, respectively for staurosporine, isopentanyladenine and olomoucine. The inhibition by staurosporine was non-competitive with respect to phosphoryl acceptor substrates. Western blot analysis of the immunoprecipitate showed both cdk5 and p67 (Munc-18), a putative regulator molecule of the kinase. Addition of p67 fusion protein enhanced the kinase activity of the immunoprecipitate by 60% above the basal activity. P67 elevated Ki values for both staurosporine and olomoucine. The degree of inhibition at high concentrations of these inhibitors was unaltered by exogenous p67 indicating a lack of competitive interactions with p67. The high affinity of staurosporine for cdk5 suggests that cdk5 may be one of the targets for the neurotropic effect of staurosporine. C1 NINCDS, NEUROCHEM LAB, NIH, BETHESDA, MD 20892 USA. NIMHANS, DEPT NEUROCHEM, BANGALORE, KARNATAKA, INDIA. NR 45 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD MAY PY 1996 VL 21 IS 5 BP 629 EP 636 DI 10.1007/BF02527763 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA UK805 UT WOS:A1996UK80500015 PM 8726973 ER PT J AU Cook, JA Wink, DA Blount, V Krishna, MC Hanbauer, I AF Cook, JA Wink, DA Blount, V Krishna, MC Hanbauer, I TI Role of antioxidants in the nitric oxide-elicited inhibition of dopamine uptake in cultured mesencephalic neurons. Insights into potential mechanisms of nitric oxide-mediated neurotoxicity SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article ID H-3 DOPAMINE; OXIDATION; TRANSPORTER; COMPLEXES; RADICALS; RELEASE; BINDING; BRAIN; AGENT; RATS AB Under aerobic conditions the addition of (C2N5)(2)N(N[O]NO)(-). Na+(DEA/NO), S-nitroso-N-acetyl penicillamine and nitric oxide (NO)-saturated buffer, but not S-nitroso-L-glutathione, to dopamine solutions resulted in dopamine o-semiquinone formation that was dependent on the formation of a NO/oxygen intermediate. High pressure liquid chromatography (HPLC) electrochemical analysis of dopamine demonstrated that the DEA/NO-induced oxidation of dopamine was abrogated in the presence of the antioxidants, ascorbate and glutathione. NO spontaneously released from DEA/NO decreased [H-3]dopamine accumulation in primary cultures of mesencephalic neurons in a dose-dependent fashion. In contrast, [H-3]gamma-aminobutyric acid uptake by mesencephalic neurons tested under the same conditions as unchanged. When DEA/NO was added to incubation buffer that contained [H-3]dopamine and the antioxidant, ascorbate or glutathione, [H-3]dopamine uptake was also inhibited. These data excluded that oxidation of extracellular [H-3]dopamine by the intermediates of the NO/O-2 reaction could have caused this decrease. Instead, NO may have acted directly on a nor yet identified target operative in the regulation of dopamine storage and release. Analysis of the rate constants for the NO reaction with ascorbate, glutathione and dopamine revealed that dopamine quinone formation was delayed by the presence of antioxidants. Since the formation of NO as well as neurotransmitter release are activated during ischemia reperfusion injury it is possible that prolonged NO exposure could deplete antioxidants and facilitate the oxidation of dopamine and thereby cause neurotoxicity. C1 NCI,RADIAT BIOL BRANCH,BETHESDA,MD 20892. NHLBI,LAB MOLEC IMMUNOL,BETHESDA,MD 20892. NR 27 TC 32 Z9 32 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD MAY-JUN PY 1996 VL 28 IS 5-6 BP 609 EP 617 DI 10.1016/0197-0186(95)00125-5 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA UQ604 UT WOS:A1996UQ60400017 PM 8792343 ER PT J AU Bernardini, R Iurato, MP Chiarenza, A Lempereur, L Calogero, AE Sternberg, EM AF Bernardini, R Iurato, MP Chiarenza, A Lempereur, L Calogero, AE Sternberg, EM TI Adenylate-cyclase-dependent pituitary adrenocorticotropin secretion is defective in the inflammatory-disease-susceptible Lewis rat SO NEUROENDOCRINOLOGY LA English DT Article DE corticotropin; adenylate cyclase; signal transduction; Lewis rat; inflammation ID CORTICOTROPIN-RELEASING FACTOR; ACTH-SECRETION; HORMONE; GLUCOCORTICOIDS; ARTHRITIS; INVITRO; BRAIN AB Susceptibility to arthritis in the Lewis rat is associated with a defect of the hypothalamic-pituitary-adrenal axis. We examined the pituitary corticotropes of both intact and dexamethasone-treated male and female inflammatory-disease-susceptible Lewis and inflammatory-disease-resist ant Fischer rats. We determined adrenocorticotropin levels in the media from primary cultures of anterior pituitary cells of both strains. In other experiments we have measured intracellular cyclic adenosine monophosphate and inositol monophosphate accumulation. Cells were incubated with corticotropin-releasing hormone, arginine vasopressin, forskolin, phorbol myristate acetate, or thyrotropin-releasing hormone. Corticotropin-releasing hormone stimulated adrenocorticotropin secretion from both male and female Lewis rat pituitary cells in a concentration-dependent manner. Basal and stimulated adrenocorticotropin levels in cells from Lewis rats were lower than those measured in the incubation media of Fischer rat dispersed pituitary cells. Arginine vasopressin, as well as forskolin and phorbol myristate acetate, induced a significant release of adrenocorticotropin from pituitary cells of both strains. Incubation with corticotropin-releasing hormone did not produce a significant accumulation of intracellular cyclic adenosine monophosphate in Lewis rat dispersed pituicytes of both sexes. On the other hand, forskolin induced a significant increase of intracellular cyclic adenosine monophosphate in the same cultures. Finally, inositol monophosphate accumulation was comparable in pituitary cells from both Lewis and Fischer rats of both sexes incubated with thyrotropin-releasing hormone. Adrenocorticotropin secretion from pituitary cells of male Lewis rats treated in vivo with dexamethasone was either reduced or abolished following incubation with different secretagogues. A defect in pituitary adrenocorticotropin secretion could be among the causes of the hyporesponsiveness of the hypothalamic-pituitary-adrenal axis in the Lewis rat. Such a defect appears to be associated with dysfunction of receptor-coupled events related to adenylate cyclase. C1 UNIV CATANIA,SCH MED,DEPT INTERNAL MED,I-95125 CATANIA,ITALY. FAC MED NECKER ENFANTS MALAD,INSERM U344,PARIS,FRANCE. CNR,SNC,IST BIOIMMAGINI & FISIOPATOL,CATANIA,ITALY. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. RP Bernardini, R (reprint author), UNIV CATANIA,SCH MED,IMMUNOPHARMACOL UNIT,INST PHARMACOL,VIALE ANDREA DORIA 6,I-95125 CATANIA,ITALY. OI bernardini, renato/0000-0002-4765-0663 NR 20 TC 8 Z9 8 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD MAY PY 1996 VL 63 IS 5 BP 468 EP 474 DI 10.1159/000127073 PG 7 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA UL868 UT WOS:A1996UL86800010 PM 8738585 ER PT J AU Hallett, M Daroff, RB AF Hallett, M Daroff, RB TI Blepharospasm: Report of a workshop SO NEUROLOGY LA English DT Editorial Material ID BLINK REFLEX; FOCAL DYSTONIAS; BASAL GANGLIA; LESIONS; EXCITABILITY; MONKEY C1 CASE WESTERN RESERVE UNIV,SCH MED,DEPT NEUROL,CLEVELAND,OH 44106. RP Hallett, M (reprint author), NINCDS,NIH,HUMAN MOTOR CONTROL SECT,BLDG 10,ROOM 5N226,10 CTR DR MSC 1428,BETHESDA,MD 20892, USA. NR 43 TC 42 Z9 43 U1 0 U2 2 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1996 VL 46 IS 5 BP 1213 EP 1218 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA UK628 UT WOS:A1996UK62800004 PM 8628455 ER PT J AU Grafman, J Schwab, K Warden, D Pridgen, A Brown, HR Salazar, AM AF Grafman, J Schwab, K Warden, D Pridgen, A Brown, HR Salazar, AM TI Frontal lobe injuries, violence, and aggression: A report of the Vietnam Head Injury Study SO NEUROLOGY LA English DT Article ID EPISODIC-DYSCONTROL; NEUROLOGY; BEHAVIOR; DYSFUNCTION; LOCATION; VETERANS; LESIONS AB Knowledge stored in the human prefrontal cortex may exert control over more primitive behavioral reactions to environmental provocation. Therefore, following frontal lobe lesions, patients are more likely to use physical intimidation or verbal threats in potential or actual confrontational situations. To test this hypothesis, we examined the relationship between frontal lobe lesions and the presence of aggressive and violent behavior. Fifty-seven normal controls and 279 veterans, matched for age, education, and time in Vietnam, who had suffered penetrating head injuries during their service in Vietnam, were studied. Family observations and self-reports were collected using scales and questionnaires that assessed a range of aggressive and violent attitudes and behavior. Two Aggression/Violence Scale scores, based on observer ratings, were constructed. The results indicated that patients with frontal ventromedial lesions consistently demonstrated Aggression/Violence Scale scores significantly higher than controls and patients with lesions in other brain areas. Higher Aggression/Violence Scale scores were generally associated with verbal confrontations rather than physical assaults, which were less frequently reported. The presence of aggressive and violent behaviors was not associated with the total size of the lesion nor whether the patient had seizures, but was associated with a disruption of family activities. These findings support the hypothesis that ventromedial frontal lobe lesions increase the risk of aggressive and violent behavior. C1 UNIFORMED SERV UNIV HLTH SCI,DEF & VET HEAD INJURY PROGRAM,BETHESDA,MD 20814. RP Grafman, J (reprint author), NINCDS,NIH,MED NEUROL BRANCH,COGNIT NEUROSCI SECT,BLDG 10,ROOM 5S209,10 CTR DR MSC 1440,BETHESDA,MD 20892, USA. OI Grafman, Jordan H./0000-0001-8645-4457 NR 54 TC 357 Z9 364 U1 7 U2 39 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1996 VL 46 IS 5 BP 1231 EP 1238 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA UK628 UT WOS:A1996UK62800007 PM 8628458 ER PT J AU Morens, DM Grandinetti, A Waslien, CI Park, CB Ross, GW White, LR AF Morens, DM Grandinetti, A Waslien, CI Park, CB Ross, GW White, LR TI Case-control study of idiopathic Parkinson's disease and dietary vitamin E intake SO NEUROLOGY LA English DT Article ID EPIDEMIOLOGY; HAWAII; MEN AB A nested case-control study of 84 incident cases of patients with idiopathic Parkinson's disease (PD) detected by June 30, 1994 and 336 age-matched control subjects, compared previously-documented intake of total dietary vitamin E and of selected vitamin E-containing foods, All study subjects had been followed for 27 to 30 years after diet recording in the 8,006-man Honolulu Heart Study cohort. We determined PD outcomes by periodic cohort re-examination and neurologic testing, private physician reports, examination of O'ahu neurologists' office records, and continual death certificate and hospital discharge diagnosis surveillance. Data on vitamin E intake, obtained from three dietary data sets at the time of cohort enrollment (1965 to 1968), included a food-frequency questionnaire and a 24-hour photograph-assisted dietary recall administered by trained dietitians. Although absence of PD was significantly associated with prior consumption of legumes (adjusted OR = 0.27, 95% CI 0.09 to 0.78), a dietary variable preselected for high vitamin E content, neither food categories nor quartiles nor continuous variables of vitamin E consumption were significantly associated with PD occurrence, Though consistent with prior reports of PD protection afforded by legumes, and with speculation on the possible benefits of dietary or supplemental vitamin E in preventing PD, these preliminary data do not conclusively document a beneficial effect of dietary vitamin E on PD occurrence. C1 UNIV HAWAII,SCH PUBL HLTH,DEPT PUBL HLTH,HONOLULU,HI 96822. UNIV HAWAII,SCH MED,DEPT TROP MED,HONOLULU,HI 96822. NIA,NIH,EAST WEST CTR,HONOLULU,HI. NIA,NIH,NAT HAWAII HLTH PROGRAM,HONOLULU,HI. NIA,NIH,QUEENS MED CTR,HONOLULU,HI. NIA,NIH,US DEPT VET AFFAIRS,HONOLULU,HI. NIA,NIH,HONOLULU ASIA AGING STUDY,HONOLULU,HI. FU NINDS NIH HHS [NS 30371] NR 34 TC 48 Z9 48 U1 1 U2 4 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1996 VL 46 IS 5 BP 1270 EP 1274 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA UK628 UT WOS:A1996UK62800014 PM 8628465 ER PT J AU Sivakumar, K Vasconcelos, O Goldfarb, L Dalakas, MC AF Sivakumar, K Vasconcelos, O Goldfarb, L Dalakas, MC TI Late-onset muscle weakness in partial phosphofructokinase deficiency: A unique myopathy with vacuoles, abnormal mitochondria, and absence of the common exon 5 intron 5 junction point mutation SO NEUROLOGY LA English DT Article ID DISEASE; GENE; DEFECT AB Three patients (ages 51, 59, and 79) from two generations of an Ashkenazi Jewish family had partial (33% activity) phosphofructokinase (PFK) deficiency that presented with fixed muscle weakness after the age of 50 years. MR spectroscopy revealed accumulation of phosphomonoesters during exercise. Muscle biopsy showed a vacuolar myopathy with increased autophagic activity and several ragged-red and cytochrome c oxidase-negative fibers. The older patient, age 79 at biopsy, had several necrotic fibers. Electron microscopy revealed subsarcolemmal and intermyofibrillar glycogen accumulation and proliferation of mitochondria with paracrystalline inclusions, probably related to reduced availability of energy due to impaired glycolysis. The common point mutation of exon 5/intron 5 junction seen in Jewish Ashkenazi patients with PFK deficiency was excluded. We conclude that late-onset fixed muscle weakness occurs in partial PFK deficiency and it may represent the end result of continuing episodes of muscle fiber destruction. Partial enzyme deficiency in two successive generations suggests a unique molecular mechanism. C1 NINCDS,NEUROMUSCULAR DIS SECT,NIH,BETHESDA,MD 20892. NINCDS,CLIN NEUROGENET UNIT,NIH,BETHESDA,MD 20892. NR 23 TC 12 Z9 12 U1 0 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1996 VL 46 IS 5 BP 1337 EP 1342 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA UK628 UT WOS:A1996UK62800027 PM 8628478 ER PT J AU Ikoma, K Samii, A Mercuri, B Wassermann, EM Hallett, M AF Ikoma, K Samii, A Mercuri, B Wassermann, EM Hallett, M TI Abnormal cortical motor excitability in dystonia SO NEUROLOGY LA English DT Article ID RECIPROCAL INHIBITION; SPASMODIC TORTICOLLIS; PARKINSONS-DISEASE; EVOKED-POTENTIALS; WRITERS CRAMP; SILENT PERIOD; BLINK REFLEX; STIMULATION; CORTEX; RESPONSES AB To assess the excitability of the motor system, we studied 11 patients with task-specific dystonia and 11 age-matched normal subjects. The dominant side was affected in nine of the patients. We delivered transcranial magnetic stimuli at different stimulus intensities and with different levels of muscle facilitation to the side contralateral to the side of electromyographic recording, and recorded motor evoked potentials (MEPs) from the flexor carpi radialis muscles bilaterally. The threshold intensity for eliciting MEPs at rest did not differ between patients and normal subjects. We compared the affected side in patients with the dominant side in normal subjects. With facilitation, the percentage of the area of the MEP to the M wave (MEP area%) was similar in both groups at low stimulus intensities, but with increasing stimulus intensity the increase in the MEP area% was greater in patients than in normal subjects (ANOVA, p < 0.001). The increase in MEP area% was similar in bath groups with increasing facilitation levels. The duration of the silent period was similar in patients and normal subjects. We conclude that cortical motor excitability is increased in dystonia. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,NIH,BETHESDA,MD 20892. RI Ikoma, Katsunori/D-8158-2012; Abbott, J./B-2976-2008 OI Abbott, J./0000-0001-6468-7284 NR 30 TC 187 Z9 188 U1 1 U2 5 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1996 VL 46 IS 5 BP 1371 EP 1376 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA UK628 UT WOS:A1996UK62800033 PM 8628484 ER PT J AU Samii, A Wassermann, EM Ikoma, K Mercuri, B Hallett, M AF Samii, A Wassermann, EM Ikoma, K Mercuri, B Hallett, M TI Characterization of postexercise facilitation and depression of motor evoked potentials to transcranial magnetic stimulation SO NEUROLOGY LA English DT Article ID LONG-TERM POTENTIATION; SOLEUS H-REFLEX; VOLUNTARY CONTRACTIONS; LASTING POTENTIATION; HUMAN-MUSCLE; FATIGUE; CORTEX; MECHANISMS; NEURONS; CAT AB We studied the effects of exercise on motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES). Subjects performed 30-second periods of isometric exercise of the extensor carpi radialis until fatigue, which was defined as the inability to maintain half maximum force. The amplitude of MEPs to TMS recorded from the resting muscle after each exercise period was on average more than twice the pre-exercise value (postexercise MEP facilitation). After fatigue occurred, the MEP amplitudes were approximately 60% of the pre-exercise value (postexercise MEP depression). There was a gradual recovery of the depressed MEPs to pre-exercise values over several minutes of rest. Postexercise MEP facilitation was constant when exercise intensity ranged from 10 to 50% of maximum voluntary contraction and it decayed to baseline over several minutes after the end of exercise. There was no postexercise MEP facilitation to TES. We hypothesize that both postexercise MEP facilitation and MEP depression are due to intracortical mechanisms. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,NIH,BETHESDA,MD 20892. RI Ikoma, Katsunori/D-8158-2012 NR 39 TC 131 Z9 132 U1 0 U2 2 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1996 VL 46 IS 5 BP 1376 EP 1382 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA UK628 UT WOS:A1996UK62800034 PM 8628485 ER PT J AU Wichman, A Foa, R AF Wichman, A Foa, R TI Ethics education in neurology residency programs: Results of a survey SO NEUROLOGY LA English DT Article C1 GEORGETOWN UNIV,VIRGINIA MED ASSOCIATES,WASHINGTON,DC. GEORGETOWN UNIV,CTR BIOETH,WASHINGTON,DC. RP Wichman, A (reprint author), NIH,OFF HUMAN SUBJECTS RES,BLDG 10,RM 1C-116,MSC 1154,BETHESDA,MD 20892, USA. NR 10 TC 5 Z9 5 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1996 VL 46 IS 5 BP 1481 EP 1483 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA UK628 UT WOS:A1996UK62800056 PM 8628507 ER PT J AU Malhotra, AK Pinals, DA Weingartner, H Sirocco, K Missar, CD Pickar, D Breier, A AF Malhotra, AK Pinals, DA Weingartner, H Sirocco, K Missar, CD Pickar, D Breier, A TI NMDA receptor function and human cognition: The effects of ketamine in healthy volunteers SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE ketamine; cognition; memory; psychotic disorders; receptors, N-methyl-d-aspartate, receptors, glutamate ID LONG-TERM POTENTIATION; D-ASPARTATE RECEPTORS; SELECTIVE IMPAIRMENT; MEMORY; SCHIZOPHRENIA; PHENCYCLIDINE; ANTAGONISTS; ACQUISITION; BINDING; SYSTEM AB A rapidly growing body of preclinical data has implicated the glutamatergic N-methyl-d-aspartate (NMDA) receptor in memory and other cognitive processes. There is comparatively less information about this receptor system in human cognition. We examined the effects of subanesthetic doses of ketamine, a noncompetitive NMDA receptor antagonist, on two forms of memory, free recall and recognition, as well as attention and behavior in a double-blind, placebo-controlled, 1-hour infusion in 15 healthy volunteers. Ketamine produced decrements in free recall, recognition memory, and attention. In addition, ketamine induced a brief psychosis in our healthy volunteers marked by thought disorder and withdrawal-retardation. Ketamine-induced memory impairments were not accounted for by changes in subject attention and were not significantly related to psychosis ratings. These data suggest that the NMDA receptor plays a direct role in two types of explicit memory. The implications of these data for the pathophysiology of schizophrenia are discussed. C1 NIAAA,DIV INTRAMURAL CLIN & BIOL RES,BETHESDA,MD 20892. RP Malhotra, AK (reprint author), NATL INST MENTAL HLTH,EXPTL THERAPEUT BRANCH,9000 ROCKVILLE PIKE BLDG 10,ROOM 4N212,BETHESDA,MD 20892, USA. NR 35 TC 412 Z9 420 U1 1 U2 21 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 1996 VL 14 IS 5 BP 301 EP 307 DI 10.1016/0893-133X(95)00137-3 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA UF561 UT WOS:A1996UF56100001 PM 8703299 ER PT J AU Reinhardt, RR Bondy, CA AF Reinhardt, RR Bondy, CA TI Differential cellular pattern of gene expression for two distinct cGMP-inhibited cyclic nucleotide phosphodiesterases in developing and mature rat brain SO NEUROSCIENCE LA English DT Article DE phosphodiesterase; enzyme; cAMP; brain insulin; mRNA ID GROWTH FACTOR-I; MOLECULAR-CLONING; NITRIC-OXIDE; INSULIN; PHARMACOLOGY; MATURATION; MESSENGER; RECEPTOR; ADENYLYL; NEURONS AB Cyclic GMP-inhibited phosphodiesterases are characterized by sensitivity of cAMP hydrolysis to inhibition by cGMP. This phosphodiesterase family contains at least two different isoforms (PDE3A and PDE3B) encoded by distinct genes and serving tissue-specific roles in regulation of lipolysis, glycogenolysis, myocardial contractility, and smooth muscle relaxation. Our previous work indicated an abundance of these two phosphodiesterase messenger RNAs in the embryonic rat brain, and therefore, to elucidate the potential functions of these enzymes in brain development as well as in mature brain function, the present study mapped cellular patterns of gene expression for these two enzymes from embryonic day 15 to adulthood using in situ hybridization histochemistry. Phosphodiesterase 3B isoform messenger RNA is uniformly expressed in germinal neuroepithelium and mature neurons, with distribution generally reflecting cell density. Phosphodiesterase isoform 3A messenger RNA, in contrast, demonstrates striking spatiotemporal specificity of expression, with three distinct patterns being evident. Firstly, this mRNA is highly abundant in both primary and secondary neuroepithelial germinal zones. Secondly, during early postnatal development PDE3A mRNA is transiently but highly expressed in neurons localized in basal forebrain, deep cerebellar, pontine, interpeduncular and a variety of thalamic, midbrain and brainstem nuclei. Thirdly, PDE3A mRNA is focally expressed in isolated large striatal and hippocampal neurons from the perinatal period without attenuation into adulthood. In summary, two cGMP-inhibited phosphodiesterase isoforms show distinctive patterns of gene expression in brain: PDE3B gene expression is uniform without evidence of system specificity or developmental stage specificity, suggesting that this isoform has a constitutive role in neuroepithelial metabolism, while PDE3B gene expression demonstrates a high level of spatiotemporal heterogeneity, suggesting that this isoform subserves a variety of developmental stage-specific and system-specific functions. RP Reinhardt, RR (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,NIH,BLDG 10,ROOM 10N-262,BETHESDA,MD 20892, USA. NR 29 TC 26 Z9 27 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD MAY PY 1996 VL 72 IS 2 BP 567 EP 578 DI 10.1016/0306-4522(95)00520-X PG 12 WC Neurosciences SC Neurosciences & Neurology GA UF982 UT WOS:A1996UF98200025 PM 8737425 ER PT J AU Katki, H Weiss, GH Kiefer, JE Taitelbaum, H Spencer, RGS AF Katki, H Weiss, GH Kiefer, JE Taitelbaum, H Spencer, RGS TI Optimization of magnetization transfer experiments to measure first-order rate constants and spin-lattice relaxation times SO NMR IN BIOMEDICINE LA English DT Article ID CREATINE-KINASE KINETICS AB A recent analysis of the optimization of magnetization transfer experiments to estimate first-order rate constants is extended to the design of experiments for measuring these constants and T-1 when both parameters are initially unknown, When the number of measurement times is fixed, an optimal design will consist of a set of measurement times which ensures that the precision of the estimates of the combination of k and T-1 is as small as possible in a worst-case scenario. Simple expressions are given for the parameters that characterize the optimal design. C1 NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892. CARNEGIE MELLON UNIV,DEPT STAT,PITTSBURGH,PA 15213. BAR ILAN UNIV,DEPT PHYS,IL-52900 RAMAT GAN,ISRAEL. NIA,NIH,CELLULAR & MOL BIOL LAB,BALTIMORE,MD 21224. RI Katki, Hormuzd/B-4003-2015 NR 14 TC 7 Z9 7 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD MAY PY 1996 VL 9 IS 3 BP 135 EP 139 DI 10.1002/(SICI)1099-1492(199605)9:3<135::AID-NBM404>3.0.CO;2-H PG 5 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA VK944 UT WOS:A1996VK94400006 PM 8892400 ER PT J AU Lambert, C Mease, RC Avren, L Le, T Sabet, H McAfee, JG AF Lambert, C Mease, RC Avren, L Le, T Sabet, H McAfee, JG TI Radioiodinated (aminostyryl)pyridinium (ASP) dyes: New cell membrane probes for labeling mixed leukocytes and lymphocytes for diagnostic imaging SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE leukocyte labeling; lymphocyte labeling; (aminostyryl)pyridinium dyes; radioiodinated cell membrane probes; inflammation imaging ID ACUTE BACTERIAL-INFECTION; CHARGE-SHIFT PROBES; WHITE BLOOD-CELLS; IN-111 OXINE; AUTOLOGOUS LYMPHOCYTES; INFLAMMATORY LESIONS; MONOCLONAL-ANTIBODY; INVIVO; GRANULOCYTES; LOCALIZATION AB We prepared [I-125/I-131]iodo-(aminostyryl)pyridinium dyes from tributylstannyl precursors. ASP 7a and 7b labeled leukocytes ex vivo (70-94%) using saline with or without washing plasma from cells. Viability of peripheral blood lymphocytes (PBLs) (dogs, rats) and splenic lymphocytes (rats) labeled with 7a and 7b (71-82%) was unchanged after labeling (greater than or equal to 88%). Canine 7b leukocytes showed higher uptake in inflammatory lesions than did In-111-oxine leukocytes. At 3 h, aspirates contained more radioiodine than In-111 (1.65:1 to 22:1) and radioiodine was cell bound. ROI measurements (3 h) gave abscess to contralateral knee ratios of 12.3 and 10.6 for I-131-7b vs. 4.8 and 2.3 for In-111-oxine. C1 GEORGE WASHINGTON UNIV, MED CTR, DEPT RADIOL, WASHINGTON, DC 20037 USA. NIH, BETHESDA, MD 20802 USA. FU NCI NIH HHS [5 RO1 CA32853] NR 56 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD MAY PY 1996 VL 23 IS 4 BP 417 EP 427 DI 10.1016/0969-8051(95)02101-9 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UT333 UT WOS:A1996UT33300005 PM 8832696 ER PT J AU Hollander, MC Alamo, I Fornace, AJ AF Hollander, MC Alamo, I Fornace, AJ TI A novel DNA damage-inducible transcript, gadd7, inhibits cell growth, but lacks a protein product SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MAMMALIAN-CELLS; GENE; RNA; KERATINOCYTES; HYBRIDIZATION; EXPRESSION; CHOP AB gadd7 cDNA was isolated from Chinese hamster ovary (CHO) cells on the basis of increased levels of RNA following treatment with UV radiation. The transcript for gadd7, as well as for four other gadd genes, was found to increase rapidly and coordinately following several different types of DNA damage and more slowly following other stresses that elicit growth arrest. Agents that induce gadd7 RNA include alkylating agents, suck as methyl methanesulfonate (MMS), N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and mechlorethamine HCl(HN2), oxidizing agents, such as hydrogen peroxide, and growth arrest signals, such as medium depletion (starvation). Since growth arrest is a cellular consequence of many types of DNA damage in normal cells, it was thought that gadd7 may play a role in the cellular response to DNA damage. Indeed, overexpression of gadd7 led to a decrease in cell growth. Interestingly, gadd7 cDNA does not contain an appreciable open reading frame and does not appear to encode a protein product, but instead may function at the RNA level. RP Hollander, MC (reprint author), NCI,MOLEC PHARMACOL LAB,DIV BASIC SCI,BETHESDA,MD 20892, USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 27 TC 39 Z9 41 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY 1 PY 1996 VL 24 IS 9 BP 1589 EP 1593 DI 10.1093/nar/24.9.1589 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UL787 UT WOS:A1996UL78700001 PM 8649973 ER PT J AU Stevens, J Metcalf, PA Dennis, BH Tell, GS Shimakawa, T Folsom, AR AF Stevens, J Metcalf, PA Dennis, BH Tell, GS Shimakawa, T Folsom, AR TI Reliability of a food frequency questionnaire by ethnicity, gender, age and education SO NUTRITION RESEARCH LA English DT Article DE diet; nutrients; black; ethnicity; methods; epidemiology ID REPRODUCIBILITY; VALIDITY; RECALL; WOMEN AB The reproducibility of nutrient intakes measured by a semi-quantitative food frequency questionnaire were examined in 418 African American and white men and women between the ages of 45 and 64 years. Subjects were a subset of participants in the Atherosclerosis Risk in Communities (ARIC) study. Reliability coefficients were calculated for nutrient intakes reported over a mean elapsed period of three years. Reliability coefficients tended to be higher in men than in women and higher in white Americans than in African Americans. The median reliability coefficients were 0.63 in white men, 0.48 in white women. 0.50 black men, and 0.45 in black women. Reliability coefficients tended to be higher in subjects with more than 12 years of education compared to those with less education, Also, age was associated with the size of the reliability coefficients, and participants who were 45-49 years of age tended have higher coefficients than older participants. C1 UNIV N CAROLINA,DEPT EPIDEMIOL,CHAPEL HILL,NC 27514. UNIV AUCKLAND,DEPT STAT,AUCKLAND,NEW ZEALAND. UNIV BERGEN,DEPT PUBL HLTH & PIRMARY HLTH CARE,BERGEN,NORWAY. NHLBI,BETHESDA,MD 20892. UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455. RP Stevens, J (reprint author), UNIV N CAROLINA,DEPT NUTR,CB 7400,CHAPEL HILL,NC 27514, USA. RI Tell, Grethe/G-5639-2015 OI Tell, Grethe/0000-0003-1386-1638 NR 19 TC 31 Z9 32 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD MAY PY 1996 VL 16 IS 5 BP 735 EP 745 DI 10.1016/0271-5317(96)00064-4 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA UH279 UT WOS:A1996UH27900003 ER PT J AU Timbo, B Altekruse, S Fowler, MG AF Timbo, B Altekruse, S Fowler, MG TI Breast-feeding and HIV transmission: Epidemiologic studies and their limitations SO NUTRITION RESEARCH LA English DT Article DE breast-feeding; breast milk; postnatal HIV transmission; epidemiology studies ID HUMAN-IMMUNODEFICIENCY-VIRUS; POSTNATAL TRANSMISSION; INFANTS BORN; PERINATAL TRANSMISSION; VERTICAL TRANSMISSION; CHILD TRANSMISSION; SEROPOSITIVE WOMEN; INFECTION; TYPE-1; MILK AB Postnatal human immunodeficiency virus (HIV) transmission from an HIV-infected mother to child has been attributed mostly to breast-feeding. However, the mechanism and timing of HIV transmission via breast-feeding and the risk factors for that mode of transmission are not well defined. A series of case reports and cohort studies have provided useful but incomplete information on the transmission of HIV through breast-feeding Various studies have yielded risk estimates of 15-40%. The stage of the HIV infection in the mother and the immunologic constituents of the breast milk have been suggested as important determinants of HIV transmission through breast-feeding. C1 NIAID, VACCINE TRIALS & EPIDEMIOL BRANCH, BETHESDA, MD 20892 USA. RP Timbo, B (reprint author), US FDA, CTR FOOD SAFETY & APPL NUTR, EPIDEMIOL BRANCH, HFS-728, WASHINGTON, DC 20204 USA. NR 50 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD MAY PY 1996 VL 16 IS 5 BP 759 EP 768 DI 10.1016/0271-5317(96)00067-X PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA UH279 UT WOS:A1996UH27900006 ER PT J AU Goldenberg, RL Mercer, BM Meis, PJ Cooper, RL Das, A McNellis, D AF Goldenberg, RL Mercer, BM Meis, PJ Cooper, RL Das, A McNellis, D TI Preterm prediction study: Fetal fibronectin testing and spontaneous preterm birth SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID AMNIOTIC-FLUID; INFECTION; DELIVERY AB Objective: To evaluate the presence of fetal fibronectin in the cervix and vagina as a screening test for spontaneous preterm birth. Methods: Two thousand nine hundred twenty-nine women at ten centers were routinely screened every 2 weeks from 22-24 to 30 weeks for cervical and vaginal fetal fibronectin. A positive test was defined as a value equal to or greater than 50 ng/mL. The relation between a positive test at four gestational ages and spontaneous preterm birth at various intervals after the test was determined. Results: In each testing period, 3-4% of the fetal fibronectin tests were positive. The correlation between cervical and vaginal fetal fibronectin at the same visit was always approximately 0.7 (P < .001), and that between cervical or vaginal fetal fibronectin in consecutive visits was between 0.17 and 0.25 (P < .001). The sensitivity of fetal fibronectin at 22-24 weeks to predict spontaneous preterm birth at less than 28 weeks was 0.63, and the relative risk for a positive versus negative test was 59. The specificity was always 96-98%, whereas the positive predictive value rose from 13% to 36% as the upper limit of the definition of preterm birth was increased from less than 28 to less than 37 weeks. The relative risk for spontaneous preterm birth after a positive fetal fibronectin test compared with a negative fetal fibronectin test varied substantially by testing period and by the definition of spontaneous preterm birth, but always remained greater than 4 and statistically significant. Conclusion: A positive cervical or vaginal fetal fibronectin test at 22-24 weeks predicted more than half of the spontaneous preterm births at less than 28 weeks (sensitivity 0.63). As the definition of spontaneous preterm birth was extended to include later gestational ages or when the fetal fibronectin test was performed later in pregnancy, the level of association between a positive fetal fibronectin test and spontaneous preterm birth, while remaining highly significant, tended to decrease. Although fetal fibronectin is an excellent test for predicting spontaneous preterm birth, we present no evidence that the use of this test will result in a reduction in spontaneous preterm birth. C1 NICHHD,MATERNAL FETAL MED UNITS NETWORK,BETHESDA,MD 20892. RP Goldenberg, RL (reprint author), UNIV ALABAMA,DEPT OBSTET & GYNECOL,618 S 20TH ST,OHB 452,BIRMINGHAM,AL 35233, USA. FU NICHD NIH HHS [HD21434, HD21410, HD21414] NR 10 TC 187 Z9 197 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 1996 VL 87 IS 5 BP 643 EP 648 DI 10.1016/0029-7844(96)00035-X PN 1 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA UG784 UT WOS:A1996UG78400001 PM 8677060 ER PT J AU Goldenberg, RL Thom, E Moawad, AH Johnson, F Roberts, J Cartis, SN AF Goldenberg, RL Thom, E Moawad, AH Johnson, F Roberts, J Cartis, SN TI The preterm prediction study: Fetal fibronectin, bacterial vaginosis, and peripartum infection SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID AMNIOTIC-FLUID; ASSOCIATION; PREGNANCY; DELIVERY AB Objective: To determine the relation between vaginal and upper genital tract infection and cervical-vaginal fetal fibronectin levels. Methods: We screened 2899 women at ten centers every 2 weeks from 23-24 to 30 weeks' gestation for cervical and vaginal fetal fibronectin. A positive test was defined as a level of at least 50 ng/mL. The relation between a positive test and bacterial vaginosis at 23-24 weeks and clinical or histologic chorioamnionitis at delivery plus neonatal sepsis was determined. Results: Fetal fibronectin was present in 4.0% of cervical and/or vaginal samples at 23-24 weeks and was nearly twice as common in women with bacterial vaginosis. Adjusting for the presence of bacterial vaginosis, race, and parity, women positive for fetal fibronectin were much more likely to have clinical chorioamnionitis (mean +/- standard deviation gestational age 30.6 +/- 4.1 weeks), with an odds ratio of 16.4 and 95% confidence interval of 7.1-37.8, and neonatal sepsis (6.3 and 2.0-20.0, respectively), than those who were fetal fibronectin-negative. A positive cervical fetal fibronectin test was a better predictor of clinical chorioamnionitis and neonatal sepsis than was a vaginal test or a combination of vaginal and cervical tests. Among 40 women who delivered before 32 weeks and had placental histology available for evaluation, ten had a positive cervical and/or vaginal fetal fibronectin test before delivery; all ten had histologic evidence of chorioamnionitis, compared with only 13 of 30 women (43%) who were fetal fibronectin-negative (P = .02). Conclusion: Women with bacterial vaginosis were more likely to have a positive fetal fibronectin test than uninfected women. Women with a positive fetal fibronectin test who delivered before 32 weeks' gestation all had evidence of histologic chorioamnionitis. Women positive for fetal fibronectin also had a 16-fold increase in clinical chorioamnionitis and a sixfold increase in neonatal sepsis. There is strong evidence that upper genital tract infection and cervical and/or vaginal fetal fibronectin are closely linked. C1 NICHHD,MATERNAL FETAL MED UNITS NETWORK,BETHESDA,MD 20892. RP Goldenberg, RL (reprint author), UNIV ALABAMA,DEPT OBSTET & GYNECOL,620 S 20TH ST,OHB 560,BIRMINGHAM,AL 35233, USA. OI caritis, steve/0000-0002-2169-0712 FU NICHD NIH HHS [HD21410, HD21414, HD21434] NR 19 TC 123 Z9 124 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 1996 VL 87 IS 5 BP 656 EP 660 DI 10.1016/0029-7844(96)00034-S PN 1 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA UG784 UT WOS:A1996UG78400003 PM 8677062 ER PT J AU Treadwell, MC Sherer, DM Sacks, AJ Ghezzi, F Romero, R AF Treadwell, MC Sherer, DM Sacks, AJ Ghezzi, F Romero, R TI Successful treatment of recurrent non-immune hydrops secondary to fetal hyperthyroidism SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID TWIN-TWIN TRANSFUSION; SPONTANEOUS RESOLUTION; INFECTION; DIAGNOSIS; DISEASE; GOITER AB Background: Non-immune fetal hydrops is a heterogeneous disorder with a mortality rate of 50-98%. Resolution of non-immune fetal hydrops is rare but has been reported to occur spontaneously or after targeted therapeutic measures. Case: A euthyroid gravida with Graves disease presented with a history of three prior perinatal deaths between 26 and 28 weeks' gestation, all associated with fetal hydrops. In the current pregnancy, the fetus developed hydrops at 24 weeks' gestation. Fetal hyperthyroidism, with high-output cardiac failure, was diagnosed with fetal blood sampling. After maternal therapy with propylthiouracil, resolution of the non-immune hydrops was documented and a healthy neonate subsequently delivered at term. The neonate developed transient hyperthyroidism after delivery, which required treatment for 10 weeks. Conclusion: Non-immune hydrops occurring as a result of fetal hyperthyroidism with high output cardiac failure is treatable with propylthiouracil. C1 NICHHD,PERINATOL RES BRANCH,INTRAMURAL DIV,BETHESDA,MD 20892. RP Treadwell, MC (reprint author), WAYNE STATE UNIV,HUTZEL HOSP,SCH MED,DEPT OBSTET & GYNECOL,4707 ST ANTOINE BLVD,DETROIT,MI 48201, USA. OI Ghezzi, Fabio/0000-0003-3949-5410 NR 22 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 1996 VL 87 IS 5 BP 838 EP 840 PN 2 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA UG785 UT WOS:A1996UG78500016 PM 8677108 ER PT J AU Chudacoff, RM Alexander, J Alvero, R Segars, JH AF Chudacoff, RM Alexander, J Alvero, R Segars, JH TI Tissue expansion vaginoplasty for treatment of congenital vaginal agenesis SO OBSTETRICS AND GYNECOLOGY LA English DT Article AB Background: A patient with congenital vaginal agenesis was unsuccessful in the use of dilation to create a vaginal orifice and rejected the option of a buttock graft. Case: Two tissue expanders were introduced beneath the labia majora bilaterally and slowly expanded over 4 weeks. Redundant labial tissue was advanced as a bipedicle flap to line the neovagina created intraoperatively. Postoperative stent placement and dilation resulted in a vaginal canal lined by full-thickness mucosa exceeding 8 cm in depth. Conclusion: A modified method of tissue expansion vaginoplasty using a bipedicle flap is an option for the surgical creation of a vaginal orifice. C1 NICHHD,GYNECOL RES SECT,NIH,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,NATL NAVAL MED CTR,DEPT OBSTET & GYNECOL,BETHESDA,MD. UNIFORMED SERV UNIV HLTH SCI,NATL NAVAL MED CTR,DEPT PLAST SURG,BETHESDA,MD. NR 8 TC 15 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 1996 VL 87 IS 5 BP 865 EP 868 PN 2 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA UG785 UT WOS:A1996UG78500026 PM 8677118 ER PT J AU Muccioli, C Belfort, R Podgor, M Sampaio, P deSmet, M Nussenblatt, R AF Muccioli, C Belfort, R Podgor, M Sampaio, P deSmet, M Nussenblatt, R TI The diagnosis of intraocular inflammation and cytomegalovirus retinitis in HIV-infected patients by laser flare photometry - Laser flare photometry in HIV-infected patients SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE Acquired Immunodeficiency Syndrome; cytomegalovirus retinitis; intraocular inflammation; photometry; retinitis; uveitis ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; VIRUS RETINITIS; AQUEOUS FLARE; UVEITIS; METER AB Purpose: To assess the sensitivity and specificity of the Kowa Laser Flare Photometer in screening for intraocular inflammation and cytomegalovirus retinitis in HIV-infected patients, Patients and methods: Using the Kowa Flare-Cell 1000, 142 HIV-infected patients were evaluated for aqueous flare. Results: Patients with posterior segment disease had higher flare values (p < 0.0001). A specificity of 93% and a sensitivity of 75% was found (cutoff value of 8 photon counts/msec), For a cutoff value of 5 photon counts/msec a specificity of 59% and a sensitivity of 91% was found. Patients with cytomegalovirus retinitis had higher flare values (p < 0.0001). A specificity of 86% and a sensitivity of 75% was found for the cutoff value of 8 photon counts/msec and respectively of 53% and 91% for a cutoff value of 5 photon counts/msec. Assuming a 30% prevalence of cytomegalovirus retinitis in the HIV-infected population, positive predictive values of 70% (cutoff value of 8 photon counts/msec) and 45% (cutoff value of 5 photon counts/msec) were estimated. Conclusions: The clinical use of laser flare photometry may assist in the diagnosis of intraocular inflammation in HIV-infected patients. The authors recommend screening of HIV-infected patients by laser flare photometry, and, if high flare values are detected, they recommend that such patients have a full eye examination and be considered at risk of having more extensive disease. This technique does not replace a full ophthalmological examination if there are predisposing visual complaints. C1 HOSP SAO PAULO,PAULISTA SCH MED,DEPT OPHTHALMOL,SAO PAULO,BRAZIL. CTR REFERENCIA & TREINAMENTO AIDS,SAO PAULO,BRAZIL. NEI,BIOMETRY & EPIDEMIOL PROGRAM,BETHESDA,MD 20892. NEI,NIH,BETHESDA,MD 20892. RI Belfort Jr, Rubens/E-2252-2012; Muccioli, Cristina/C-3419-2013; OI Belfort Jr, Rubens/0000-0002-8422-3898; de Smet, Marc/0000-0002-9217-5603 NR 17 TC 6 Z9 6 U1 0 U2 0 PU AEOLUS PRESS PI BUREN PA PO BOX 740, 4116 ZJ BUREN, NETHERLANDS SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD MAY PY 1996 VL 4 IS 2 BP 75 EP 81 DI 10.3109/09273949609079636 PG 7 WC Ophthalmology SC Ophthalmology GA VV673 UT WOS:A1996VV67300001 PM 22827411 ER PT J AU Egwuagu, CE Smith, JA Kozhich, AT Mahdi, RM AF Egwuagu, CE Smith, JA Kozhich, AT Mahdi, RM TI Usage of TCR V gamma 2(+) T lymphocytes in experimental autoimmune uveoretinitis SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE experimental autoimmune uveoretinitis; T cell receptor; gamma delta T cells; autoimmune disease; uveitis; interphotoreceptor retinoid binding protein; S-Antigen ID RETINOID-BINDING PROTEIN; CELL RECEPTOR; S-ANTIGEN; IRBP; UVEITIS; GENE; DETERMINANT; PINEALITIS; EAU; RAT AB Experimental autoimmune uveoretinitis (EAU) is a T cell mediated autoimmune disease that selves as a model of human intraocular inflammatory disease (uveitis). It is initiated in susceptible animals by immunization with retinal antigens, such as interphotoreceptor retinoid binding protein (IRBP) and S-Antigen (SAg) or by adoptive transfer of ocular Ag-specific uveitogenic T cells. Previous studies of T cell receptor (TCR) usage by uveitogenic T cells have implicated V beta 8(+)-expressing T cells in the pathogenesis of EAU. Here, the authors have analyzed the TCR V gamma repertoire in the retinas of Lewis rats with and without EAU as well as the repertoire of several SAg- or IRBP-specific T cell lines. They detected V gamma 2 transcripts in all four pathogenic Lines and in the retinas of Lewis rats with EAU but not in the two non-pathogenic lines nor in the retinas of naive rats. V gamma 7 transcripts were detected in RNAs obtained from the retina, regardless of whether the rat had EAU or not. However, the authors could not detect V gamma 4, V gamma or V gamma 6 TCR transcripts in any of the samples analyzed. Taken together, their data suggests a correlation between recruitment of V gamma 2(+) T cells and EAU pathogenesis. RP Egwuagu, CE (reprint author), NEI,IMMUNOL LAB,NIH,10 CTR DR,MSC 1850,BETHESDA,MD 20892, USA. NR 25 TC 0 Z9 0 U1 0 U2 0 PU AEOLUS PRESS PI BUREN PA PO BOX 740, 4116 ZJ BUREN, NETHERLANDS SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD MAY PY 1996 VL 4 IS 2 BP 105 EP 112 DI 10.3109/09273949609079640 PG 8 WC Ophthalmology SC Ophthalmology GA VV673 UT WOS:A1996VV67300005 PM 22827415 ER PT J AU Chew, PH Bush, DE Engel, BT Talan, MI Abell, RT AF Chew, PH Bush, DE Engel, BT Talan, MI Abell, RT TI Overnight heart rate and cardiac function in patients with dual chamber pacemakers SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE circadian; heart failure; pacemaker artificial; heart rate ID SYMPATHETIC-NERVE ACTIVITY; UNITED-STATES; PACING PRACTICES; FAILURE; SLEEP; TACHYCARDIA; OUTPUT; VOLUME AB Animal data indicate that chronic, overnight pacing at normal evening heart rates impairs cardiac function. We examined the relationship of pacing rate and cardiac function in nine patients with dual-chamber pacemakers. We investigated two, 3-week pacing regimens (80 and 50 ppm : DDD mode) in a cross-over design. Doppler echocardiograms were performed at 1700 hours (PM) and 0600 hours (AM) at the end of each regimen. Ventricular function and preload decreased overnight (PM vs AM) with both pacing regimens. Compared to the morning values, the ratio of preejection to ejection time (PEP/ET) rose (0.43 vs 0.46), while the mean velocity of circumferential fiber shortening (V-cf) fell (1.16 cm/s vs 1.11 cm/s). Stroke volume (SV) (61 mL vs 53 mL) and ejection fraction (EF) also fell (0.56 vs 0.53) in the morning. End-diastolic volume (EDV) (94 mL vs 88 mL) decreased in the morning, as did the ratio of passive to active filling (E/A) (1.06 vs 0.96). Isovolumic relaxation time (91 ms vs 101 ms) increased overnight at both pacing rates. Systolic function decreased at 80 ppm relative to 50 ppm at both times of day. SV fell (54 mL vs 61 mL), while both EDVn (92 mL vs 90 mL) and end-systolic volume (ESV) increased (43 mL vs 40 mL). Contractility measured by V-cf (2.09 cm/s vs 1.18 cm/s) and PEP/ET (0.49 vs 0.41) was reduced at 80 ppm. The heart needs to rest at night by slowing ifs rate of contraction. Pacing at 80 ppm impairs systolic and diastolic ventricular compared to 50 ppm. Longer term consequences of ostensibly physiological pacing rates merit inquiry, particularly in those with preexisting cardiac dysfunction. C1 NIA,GERONTOL RES CTR,BEHAV SCI LAB,NIH,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,BAYVIEW MED CTR,DIV CARDIOL,BALTIMORE,MD. BRISTOL MYERS SQUIBB CO,PHARMACEUT RES INST,PRINCETON,NJ. FU NCRR NIH HHS [5 M01 RR02719] NR 23 TC 6 Z9 7 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD MAY PY 1996 VL 19 IS 5 BP 822 EP 828 DI 10.1111/j.1540-8159.1996.tb03365.x PG 7 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA UK361 UT WOS:A1996UK36100011 PM 8734750 ER PT J AU Favara, BE AF Favara, BE TI Histopathology of the liver in histiocytosis syndromes SO PEDIATRIC PATHOLOGY & LABORATORY MEDICINE LA English DT Article DE hemophagocytic syndrome; histiocytosis; juvenile,; xanthogranuloma; Langerhans cell histiocytosis; liver mononuclear phagocytic system; Rosai-Dorfman disease; von Kupffer cell ID JUVENILE XANTHOGRANULOMA; HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; SINUS HISTIOCYTOSIS; CHILDREN; LESION AB Liver biopsies were studied in 47 cases representing various histiocytosis syndromes. These included 32 cases of hemophagocytic syndrome, 11 cases of langerhans cell histiocytosis (LCH), and 4 cases of other histiocytic disorders. All cases of hemophagocytic syndrome, except one with cytomegalovirus infection, displayed portal lymphohistiocytic infiltrates dominated by T lymphocytes. Activation of the hepatic mononuclear phagocytic system (MPS), evidence by enlarged von Kupffer cells, some of which were hemophagocytic, was seen in 28 cases of hemophagocytic syndrome. Endothelial enlargement, minor degrees of hepatocellular degeneration, and steatosis were also noted. Ten of the 11 cases of LCH also showed activation of the MPS. It was the only lesion in two biopsies. Seven cases demonstrated nonspecific ''traiditis.'' In three this was associated with cholangiocentric and random acinar histiocytic lesions. Evidence of activation of the MPS was also observed in both cases of Rosoai-Dorfman disease and was accompanied by acinar histiocytic lesions in one and triaditis in the other. Likewise, both cases of juvenile xanthogranuloma showed activation of the MPS and focal granulomatous lesions. It is concluded that activation of the MPS is a common feature of liver disease in histiocytosis syndromes and that hepatic enlargement may be the result of this process instead of, or in addition to, the liver lesions known to be featured in these disorders. Hepatic lesions of the various histiocytosis syndromes resemble typical lesions in other sites and, in some instances, are accompanied by nonspecific changes. These nonspecific changes may occur in the absence of lesions that are diagnositic or typical of the particular histiocytosis syndrome. The location and character of hepatic lesions are important factors in the significance of liver involvement. C1 NATL INST HLTH,PERSISTENT VIRAL DIS LAB,ROCKY MT LABS,HAMILTON,MT. NR 25 TC 38 Z9 39 U1 0 U2 0 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 1077-1042 J9 PEDIATR PATHOL LAB M JI Pediatr. Pathol. Lab. Med. PD MAY-JUN PY 1996 VL 16 IS 3 BP 413 EP 433 PG 21 WC Pathology; Pediatrics SC Pathology; Pediatrics GA UL715 UT WOS:A1996UL71500005 PM 9025843 ER PT J AU Nelson, KB Grether, J AF Nelson, KB Grether, J TI Cerebral palsy in very low birth weight infants, pre-eclampsia and magnesium sulphate - Reply SO PEDIATRICS LA English DT Letter C1 CALIF BIRTH DEFECTS MONITORING PROGRAM,EMERYVILLE,CA 94608. RP Nelson, KB (reprint author), NINCDS,NEUROEPIDEMIOL BRANCH,NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAY PY 1996 VL 97 IS 5 BP 781 EP 782 PG 2 WC Pediatrics SC Pediatrics GA UH758 UT WOS:A1996UH75800045 ER PT J AU Veech, RL AF Veech, RL TI Physiological approaches to increase biocompatibility of peritoneal dialysis SO PERITONEAL DIALYSIS INTERNATIONAL LA English DT Letter RP Veech, RL (reprint author), US DEPT HHS,NIH,BELTSVILLE,MD, USA. NR 4 TC 4 Z9 4 U1 0 U2 1 PU MULTIMED INC PI TORONTO PA 1120 FINCH AVE WEST SUITE 601, TORONTO ON M3J 3H7, CANADA SN 0896-8608 J9 PERITON DIALYSIS INT JI Perit. Dial. Int. PD MAY-JUN PY 1996 VL 16 IS 3 BP 332 EP 332 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA UN312 UT WOS:A1996UN31200024 PM 8761557 ER PT J AU Chauthaiwale, JV Sakai, T Taylor, SE Ambudkar, IS AF Chauthaiwale, JV Sakai, T Taylor, SE Ambudkar, IS TI Presence of two Ca2+ influx components in internal Ca2+-pool-depleted rat parotid acinar cells SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE Ca2+ entry; kinetics; thapsigargin; parotid cells; fura-2 ID DIVALENT-CATION ENTRY; MAST-CELLS; INOSITOL PHOSPHATE; CALCIUM CURRENT; TUMOR PROMOTER; CA-2+; ACTIVATION; MEMBRANE; GLAND; THAPSIGARGIN AB The molecular mechanism(s) involved in mediating Ca2+ entry into rat parotid acinar and other non-excitable cells is not known. In this study we have examined the kinetics of Ca2+ entry in fura-2-loaded parotid acinar cells, which were treated with thapsigargin to deplete internal Ca2+ pools (Ca2+-pool-depleted cells). The rate of Ca2+ entry was determined by measuring the initial increase in free cytosolic [Ca2+] ([Ca2+](i)) in Ca2--pool-depleted, and control (untreated), cells upon addition of various [Ca2+] to the medium. In untreated cells, a low-affinity component was detected with K-Ca = 3.4 +/- 0.7 mM (where K-Ca denotes affinity for Ca2+) and V-max = 9.8 +/- 0.4 nM [Ca2+](i)/s. In thapsigargin-treated cells, two Ca2+ influx components were detected with K-Ca values of 152 +/- 79 mu M (V-max = 5.1 +/- 1.9 nM [Ca2+](i)/s) and 2.4 +/- 0.9 mM (V-max = 37.6 +/- 13.6 nM [Ca2+](i)/s), respectively. We have also examined the effect of Ca2+ and depolarization on these two putative Ca2+ influx components. When cells were treated with thapsigargin in a Ca2+-free medium, Ca2+ influx was higher than into cells treated in a Ca2+-containing medium and, while there was a 46% increase in the V-max of the low-affinity component (no change in K-Ca), the high-affinity component was not clearly detected. In depolarized Ca2+-pool-depleted cells (with 50mM KCl in the medium) the high-affinity component was considerably decreased while there was an apparent increase in the K-Ca of the low-affinity component, without any change in the V-max. These results demonstrate that Ca2+ influx into parotid acinar cells (1) is increased (four- to five-fold) upon internal Ca2+ pool depletion, and (2) is mediated via at least two components, with low and high affinities for Ca2+. C1 NIDR,SECRETORY PHYSIOL SECT,CIPCB,NIH,BETHESDA,MD 20892. BAYLOR COLL DENT,DEPT ORAL & MAXILLOFACIAL SURG,DALLAS,TX 75246. NR 27 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD MAY PY 1996 VL 432 IS 1 BP 105 EP 111 DI 10.1007/s004240050111 PG 7 WC Physiology SC Physiology GA UP586 UT WOS:A1996UP58600014 PM 8662274 ER PT J AU Tella, SR AF Tella, SR TI Possible novel pharmacodynamic action of cocaine: Cardiovascular and behavioral evidence SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE cocaine; behavior; cardiovascular effects; monoamine reuptake; sodium channel; novel pharmacodynamic action ID CENTRAL-NERVOUS-SYSTEM; SCHEDULE-CONTROLLED BEHAVIOR; CONSCIOUS SQUIRREL-MONKEYS; DOPAMINE UPTAKE INHIBITOR; NEURONAL MONOAMINE UPTAKE; HEART-RATE; UPTAKE SITES; INDUCED LOCOMOTION; NONHUMAN-PRIMATES; SYMPATHOADRENAL SYSTEM AB Intravenous cocaine (0.03-3 mg/kg) produced two distinct and temporally separable effects in rats. One is an initial, large, and brief increase in blood pressure (BP) and heart rate (HR) of a rapid onset (abrupt hemodynamic stimulation). A rapid, brief, and intense behavioral arousal accompanied this abrupt hemodynamic stimulation. The other effect of cocaine is a prolonged locomotor activation of a relatively slower onset. Prolonged increases in BP and HR accompanied this locomotor effect. The threshold doses of cocaine to produce abrupt hemodynamic stimulation and locomotion are 0.03 and 0.3 mg/kg, respectively. Dopamine receptor antagonists, SCH 23390 or eticlopride, at a 0.03 mg/kg dose antagonized the locomotion and the parallel prolonged increases in BP and HR, but not the initial brief behavioral arousal and abrupt hemodynamic stimulation responses to cocaine. Peripheral dopamine receptor antagonist, domperidone, altered neither behavioral nor cardiovascular effects of cocaine. Chlorisondamine (1 mg/kg), an autonomic ganglionic blocker, did not alter either the initial brief behavioral arousal or the locomotor responses to cocaine, but it prevented the cardiovascular changes that accompanied both these behavioral responses. Norepinephrine, a direct adrenergic vasoconstrictor, although produced rapid and large increase in BP, did not cause abrupt behavioral arousal or locomotor activation. Unlike cocaine, monoamine reuptake inhibitors that are selective for norepinephrine (nisoxetine, 0.1-1 mg/kg) or serotonin (fluoxetine, 0.3-3 mg/kg) produced neither brief behavioral arousal and abrupt hemodynamic stimulation nor locomotor activation. Dopamine-selective reuptake inhibitor, GBR 12909, also did not elicit the initial brief behavioral arousal and abrupt hemodynamic stimulation. But, GBR 12909, like cocaine, produced a prolonged locomotor effect and parallel increases in BP and HR. These effects of GBR 12909 were prevented by SCH 23390 and eticlopride, but not by domperidone. Similar to cocaine, cardiovascular, but not the locomotor effects of GBR 12909 were prevented by chlorisondamine. Lidocaine (0.3-3 mg/kg), a sodium channel blocker and local anesthetic, produced neither behavioral nor physiological changes. Both cocaine (3 mg/kg) and GBR 12909 (1 mg/kg) increased plasma norepinephrine and epinephrine concentrations. These increases were antagonized by both eticlopride and SCH 23390. These results indicate that behavioral and cardiovascular effects of cocaine are intricately related with respect to the molecular mechanisms involved. Two pharmacodynamic actions of cocaine appear to mediate these effects. One is a dopamine-dependent while the other is a monoamine- and sodium channel-independent novel action. The former mediates cocaine's locomotor effect and the accompanying prolonged increases in BP and HR, while the latter mediates the initial brief behavioral arousal and the accompanying abrupt hemodynamic stimulation. C1 NIDA,ADDICT RES CTR,PRECLIN PHARMACOL LAB,BEHAV PHARMACOL & GENET SECT,BALTIMORE,MD 21224. FU NIDA NIH HHS [1R29DA08830] NR 93 TC 29 Z9 29 U1 5 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD MAY PY 1996 VL 54 IS 2 BP 343 EP 354 DI 10.1016/0091-3057(95)02145-0 PG 12 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA UN186 UT WOS:A1996UN18600006 PM 8743594 ER PT J AU GeterDouglass, B Riley, AL AF GeterDouglass, B Riley, AL TI Dopamine D-1/D-2 antagonist combinations as antagonists of the discriminative stimulus effects of cocaine SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE drug discrimination learning; cocaine ID SQUIRREL-MONKEYS; DRUG DISCRIMINATION; RECEPTOR SUBTYPES; RHESUS-MONKEYS; D-AMPHETAMINE; RATS; INVOLVEMENT; D-1; STIMULATION; QUINPIROLE AB Although data suggest that the dopaminergic system mediates the discriminative stimulus effects of cocaine, neither selective D-1 or D-2 dopamine agonists nor selective D-1 or D-2 antagonists substitute reliably for or consistently block these effects. These findings suggest that concurrent activity at these receptor subtypes may underlie this discrimination. Accordingly, it would be expected that simultaneous blockade of these receptors may be necessary to block it fully. The ability of various combinations of the D-1 antagonist, SCH 23390, and the D-2 antagonist, haloperidol, were tested for their ability to block the cocaine stimulus in rats trained to discriminate cocaine (7.5, 10, or 13 mg/kg) from vehicle. Antagonist combinations decreased the percentage of cocaine-appropriate responses 10-95% below the cocaine baseline at doses of the antagonist that were inactive when given separately. These findings support the position that activity at D-1-like and D-2-like receptor subtypes may account for more of the pharmacological action of cocaine than activation of a single dopamine receptor subtype. C1 AMERICAN UNIV,DEPT PSYCHOL,PSYCHOPHARMACOL LAB,WASHINGTON,DC 20016. RP GeterDouglass, B (reprint author), NIDA,DIV IMTRAMURAL RES,DRUG DEV GRP,PSYCHOBIOL SECT,POB 5180,BALTIMORE,MD 21224, USA. FU NIDA NIH HHS [F31DA05477] NR 42 TC 10 Z9 10 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD MAY PY 1996 VL 54 IS 2 BP 439 EP 451 DI 10.1016/0091-3057(95)02217-1 PG 13 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA UN186 UT WOS:A1996UN18600019 PM 8743607 ER PT J AU Koetzner, L Riley, AL Glowa, JR AF Koetzner, L Riley, AL Glowa, JR TI Discriminative stimulus effects of dopaminergic agents in rhesus monkeys SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE phentermine; d-amphetamine; GBR 12909; cocaine; drug abuse; drug discrimination; rhesus monkeys ID PHARMACOLOGICAL CHARACTERIZATION; REUPTAKE INHIBITORS; COCAINE; GBR-12909 AB Recent reports have shown that treatment with dopamine reuptake inhibitors can selectively decrease responding maintained by low doses of cocaine in rhesus monkeys. This may occur because response-independent delivery of a reuptake inhibitor and response-dependent cocaine have common effects. One behavioral effect that dopamine reuptake inhibitors and cocaine share is their ability to serve as a discriminative stimulus. To compare discriminative effects of several dopaminergic agents with their ability to attenuate cocaine-maintained responding, three rhesus monkeys were first trained to discriminate intravenous injections of cocaine (0.1 mg/kg) from saline. Following generalization testing with various doses of cocaine (0.001-1.0 mg/kg), the relative potencies of phentermine (0.03-1.0 mg/kg), d-amphetamine (0.01-1.0 mg/kg), GBR 12909 (0.01-1.0 mg/kg), and buspirone (0.03-0.56 mg/kg) to substitute for cocaine were assessed. Each drug except buspirone resulted in predominantly cocaine-appropriate responding at doses that were generally without rate-decreasing effect. The ED(50) for the ability of these drugs to substitute for cocaine exhibited the same rank order as that for their effectiveness in decreasing cocaine-maintained responding. Thus, the current results show that the potencies of dopaminergic drugs to decrease cocaine-maintained responding and substitute for cocaine in a drug discrimination paradigm are related. C1 NIDDK,LMC,BEHAV PHARMACOL UNIT,NIH,BETHESDA,MD 20892. AMERICAN UNIV,DEPT PSYCHOL,PSYCHOPHARMACOL LAB,WASHINGTON,DC 20016. FU ONDIEH CDC HHS [RA-ND-93-24] NR 31 TC 16 Z9 16 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD MAY PY 1996 VL 54 IS 2 BP 517 EP 523 DI 10.1016/0091-3057(95)02282-1 PG 7 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA UN186 UT WOS:A1996UN18600029 PM 8743617 ER PT J AU Middleman, MN Lush, RM Figg, WD AF Middleman, MN Lush, RM Figg, WD TI The mutated androgen receptor and its implications for the treatment of metastatic carcinoma of the prostate SO PHARMACOTHERAPY LA English DT Review ID FLUTAMIDE WITHDRAWAL SYNDROME; COMBINATION THERAPY; CANCER; INVITRO; CELLS AB Androgen deprivation is the most effective therapy for patients with advanced prostatic carcinoma. The lack of androgen stimulation on these cells causes them to become apoptotic. Although therapeutic efficacy of initial androgen deprivation in prostate cancer is high, the emergence of androgen-independent cancer is inevitable. Withdrawal of the antiandrogen flutamide elicits surprising activity in these cancers. In numerous studies the response rates cell line harbors a mutation in codon 877 of the androgen receptor. The mutant receptor loses androgen specificity and is activated by various steroids as well as flutamide. Identical and similar mutations have now been isolated from human prostate cancer tissue. The discovery of the mutated androgen receptor sheds light on the emergence of androgen-independent cancer and should facilitate the development of more efficacious therapies. C1 NCI,CLIN PHARMACOKINET SECT,CLIN PHARMACOL BRANCH,CLIN ONCOL PROGRAM,DIV CANC TREATMENT,NIH,BETHESDA,MD 20892. RI Figg Sr, William/M-2411-2016 NR 32 TC 16 Z9 16 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD MAY-JUN PY 1996 VL 16 IS 3 BP 376 EP 381 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UM605 UT WOS:A1996UM60500005 PM 8726595 ER PT J AU Dillon, J Gaillard, ER Bilski, P Chignell, CF Reszka, KJ AF Dillon, J Gaillard, ER Bilski, P Chignell, CF Reszka, KJ TI The photochemistry of the retinoids as studied by steady-state and pulsed methods SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID GENERATION; DAMAGE; LIGHT AB The retina and retinal pigment epithelium contain a number of retinoids in a metabolic pathway that eventually forms the visual pigments. This study investigates the photochemistry of those retinoids that may contribute to light-induced damage to the retina. These include retinal (RAL), retinol (ROL), retinylpalmitate (ROLpal) and the protonated Schiff-base of retinal (RAL(sb)). Their photochemistry was followed by both EPR spin-trapping techniques and the direct detection of singlet oxygen via its luminescence at 1270 nm. Irradiation (>300 nm) of RAL, ROL in methanol (MeOH) or RALpal in dimethylformamide, produces free radicals from both solvents. Illumination of RAL(sb) in MeOH containing NADH with light above 400 nm (and even above 455 nm) generates the superoxide radical. We also determined that the quantum yields for singlet oxygen sensitization by RAL, ROL or RALpal in MeOH are 0.05, 0.03 and <0.01, respectively. These values are at least 75% less than those previously found using chemical methods. These observations indicate that a major photochemical process for these retinoids may be an electron (or hydrogen) process that will lead to radical products, and that the singlet oxygen mechanism is of relatively minor importance in protic solvents. These results may explain the action spectra obtained from light-induced damage to the retina. C1 UNIV ROCHESTER,DEPT CHEM,ROCHESTER,NY. NIEHS,MOLEC BIOPHYS LAB,NIH,RES TRIANGLE PK,NC 27709. RP Dillon, J (reprint author), COLUMBIA UNIV,DEPT OPHTHALMOL,630 W 168TH ST,NEW YORK,NY 10032, USA. NR 34 TC 29 Z9 29 U1 0 U2 8 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD MAY PY 1996 VL 63 IS 5 BP 680 EP 685 DI 10.1111/j.1751-1097.1996.tb05673.x PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UH759 UT WOS:A1996UH75900020 PM 8628760 ER PT J AU Prasad, PD Hoffmans, BJ Moe, AJ Smith, CH Leibach, FH Ganapathy, V AF Prasad, PD Hoffmans, BJ Moe, AJ Smith, CH Leibach, FH Ganapathy, V TI Functional expression of the plasma membrane serotonin transporter but not the vesicular monoamine transporter in human placental trophoblasts and choriocarcinoma cells SO PLACENTA LA English DT Article ID MOLECULAR-CLONING; VESICLES; NEUROTRANSMITTERS; BINDING; STORAGE; BRAIN; MOUSE AB We investigated the functional expression of the plasma membrane serotonin transporter and the vesicular monoamine transporter in choriocarcinoma cells and normal trophoblasts. The RBL 2H3 cells, a rat basophilic leukaemia cell line, which express both transporters were used for comparison. The choriocarcinoma cells JAr and BeWo were found to possess the plasma membrane serotonin transporter as assessed by the presence of serotonin transport activity in intact cells that was Na+-dependent and was sensitive to inhibition by tricyclic and non-tricyclic antidepressants. The activity of the vesicular monoamine transporter in these cells was determined by measuring serotonin transport in digitonin-permeabilized cells. The transport in permeabilized cells was very slow, was not stimulated by ATP and was insensitive to inhibition by reserpine. Under similar conditions, the vesicular monoamine transporter activity was demonstrable in RBL cells, which was stimulated by ATP and was inhibitable by reserpine, bafilomycin Al (an inhibitor of the V-type H+-pump) and carbonyl cyanide p-trifluoromethoxy phenylhydrazone (a protonophore which dissipates transmembrane H+ gradients). In corroboration with these findings, mRNA transcripts hybridizable to the vesicular monoamine transporter cDNA probe were detectable in RBL cells but not in JAr choriocarcinoma cells. Similarly, there was no evidence for the expression of the vesicular monoamine transporter as assessed by Northern blot analysis in normal trophoblasts which were maintained in culture to differentiate to form multinucleated syncytial cells. It is concluded that the trophoblasts and choriocarcinoma cells express the plasma membrane serotonin transporter but not the vesicular monoamine transporter. (C) 1996 W. B. Saunders Company Ltd C1 MED COLL GEORGIA,DEPT BIOCHEM & MOLEC BIOL,AUGUSTA,GA 30912. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. WASHINGTON UNIV,CHILDRENS HOSP,SCH MED,DEPT PEDIAT,ST LOUIS,MO 63178. FU NICHD NIH HHS [HD 07562, HD 27258, HD 27487] NR 37 TC 37 Z9 38 U1 1 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0143-4004 J9 PLACENTA JI Placenta PD MAY PY 1996 VL 17 IS 4 BP 201 EP 207 DI 10.1016/S0143-4004(96)90039-9 PG 7 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA UN995 UT WOS:A1996UN99500002 PM 8761963 ER PT J AU Esposito, C Striker, LJ Patel, A Peten, E Liu, ZH Sakai, H Striker, GE Yang, CW Hirshmann, G Schena, P Gesualdo, T Feld, L Waz, W Huang, CC Lai, PC Huang, JY Lewis, E Orlowski, J Koide, H Horikoshi, S DAmico, G Fornasieri, A diMario, U Fuiano, G Li, L Feng, Z Jacobs, C Beaufils, H Jouanneau, C Baumelou, A Arakawa, M Nishi, S Ueno, M Sraer, JD Mignon, F Ronco, P Mougenot, B Rondeau, E Peraldi, MN Delarue, F Yagame, M Suzuki, D deStrihou, CV Pirson, Y Cosyns, JP Garbar, C Jacobson, H Fogo, A Chevalier, R Norwood, VF Thornhill, B Emancipator, S Rao, C Adler, S Beaumont, PM Hirschberg, R Nast, C Cohen, A Moore, J Carome, MA Srinsky, JJ AF Esposito, C Striker, LJ Patel, A Peten, E Liu, ZH Sakai, H Striker, GE Yang, CW Hirshmann, G Schena, P Gesualdo, T Feld, L Waz, W Huang, CC Lai, PC Huang, JY Lewis, E Orlowski, J Koide, H Horikoshi, S DAmico, G Fornasieri, A diMario, U Fuiano, G Li, L Feng, Z Jacobs, C Beaufils, H Jouanneau, C Baumelou, A Arakawa, M Nishi, S Ueno, M Sraer, JD Mignon, F Ronco, P Mougenot, B Rondeau, E Peraldi, MN Delarue, F Yagame, M Suzuki, D deStrihou, CV Pirson, Y Cosyns, JP Garbar, C Jacobson, H Fogo, A Chevalier, R Norwood, VF Thornhill, B Emancipator, S Rao, C Adler, S Beaumont, PM Hirschberg, R Nast, C Cohen, A Moore, J Carome, MA Srinsky, JJ TI Molecular analysis of glomerular diseases in renal biopsies: Initial results of a collaborative international study SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Article DE kidney glomerulus; collagen; gene expression; glomerulonephritis; membranous; glomerulosclerosis ID BASEMENT-MEMBRANE COLLAGEN; DIFFERENTIAL EXPRESSION; DIABETIC NEPHROPATHY; IV COLLAGEN; CELL AB An accurate assessment of which patient with glomerular disease will progress to end-stage renal failure would be an important addition to establishing prognosis and evaluating therapeutic strategies, We previously found the development of glomerular scarring in animal models was preceded by an increase in glomerular type IV collagen mRNAs and that the level of scarring predicted the rate of progression. The purpose of this study was to determine whether these findings apply to human glomerular diseases using microdissected glomeruli and assessment of mRNA by competitive PCR. After showing that the levels of type IV collagen mRNAs were elevated in sclerotic glomeruli isolated from nephrectomies, we undertook this preliminary cross-sectional study of type IV collagen subchain mRNAs in renal biopsies in two of the leading causes of glomerulosclerosis, diabetic nephropathy, and membranous glomerulopathy. We found that glomerular type IV collagen mRNA levels were altered in disease-specific ways. The relative levels of the individual alpha-chains of type IV collagen depended on the anatomic site of the glomerular lesions, The alpha 2 type IV/alpha 3 type IV collagen mRNA ratio was high in diabetes mellitus, but not in membranous glomerulopathy. These data, coupled with those obtained from experimental animals, suggest that a dysregulation of basement collagen synthesis underlies progressive glomerular scarring. If these conclusions are verified in prospective studies it will be feasible to assess the risk of developing progressive glomerulosclerosis in the individual patient and to quantitatively assess therapeutic responses in a timely manner. C1 NIDDK,RENAL CELL BIOL SECT,NIH,BETHESDA,MD 20892. TOKAI UNIV,SCH MED,DEPT INTERNAL MED,DIV NEPHROL & METAB,ISEHARA,KANAGAWA 25911,JAPAN. NR 14 TC 23 Z9 23 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD MAY PY 1996 VL 108 IS 3 BP 209 EP 217 PG 9 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UT132 UT WOS:A1996UT13200004 PM 8774054 ER PT J AU Wang, JTL Marr, TG Shasha, D Shapiro, BA Chirn, GW Lee, TY AF Wang, JTL Marr, TG Shasha, D Shapiro, BA Chirn, GW Lee, TY TI Complementary classification approaches for protein sequences SO PROTEIN ENGINEERING LA English DT Article DE block searching; protein classification; protein database; statistical approaches; SWISS-PROT ID BINDING-SITES; ALIGNMENT; IDENTIFICATION; DICTIONARY; GENERATION; PREDICTION; DATABASES; PATTERNS; MATRICES; SEARCH AB We have studied five methods of protein classification and have applied them to the 768 groups of related proteins in the PROSITE catalog. Four of these methods are based on searching a database of blocks, and the other uses the frequently occurring moths found in the protein families combined with a fingerprint technique, Our experimental results show that the block-based methods perform well when taking into account the probability of amino acids occurring in a block, Furthermore, the five methods give information that is complementary to each other, Thus, using the five methods together, one can obtain high confidence classifications (if the results agree) or suggest alternative hypotheses (if the results disagree), We also list those proteins whose current families documented in the PROSITE catalog differ from those suggested by our results, There are remarkably few of them, which is a testimony to the quality of PROSITE. C1 COLD SPRING HARBOR LAB, COLD SPRING HARBOR, NY 11724 USA. NYU, COURANT INST MATH SCI, NEW YORK, NY 10012 USA. NCI, IMAGE PROC SECT, MATH BIOL LAB, DIV BASIC SCI, NIH, FREDERICK, MD 21702 USA. UNIV MARYLAND, DEPT MATH, COLLEGE PK, MD 20742 USA. RP NEW JERSEY INST TECHNOL, DEPT COMP & INFORMAT SCI, NEWARK, NJ 07102 USA. FU NHGRI NIH HHS [1R01-HG0020301AI] NR 37 TC 13 Z9 13 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD MAY PY 1996 VL 9 IS 5 BP 381 EP 386 DI 10.1093/protein/9.5.381 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA UR367 UT WOS:A1996UR36700001 PM 8795038 ER PT J AU DelaCruz, X Lee, B AF DelaCruz, X Lee, B TI The structural homology between uteroglobin and the pore-forming domain of colicin A suggests a possible mechanism of action for uteroglobin SO PROTEIN SCIENCE LA English DT Article DE colicin A; lipid bilayer; membrane-binding proteins; protein structure comparisons; uteroglobin ID TRANSFER DISTANCE MEASUREMENTS; MEMBRANE-BOUND STATE; ANGSTROM RESOLUTION; REFINED STRUCTURE; DATA-BANK; PROTEIN; FRAGMENTS; CONFORMATION; ALIGNMENT; INSERTION AB Although the exact physiological function of uteroglobin is not known, it has been suggested that it may function by inhibiting phospholipase A(2). We have found that the uteroglobin fold is embedded in that of the pore-forming domain of colicin A. Colicin A is an antibiotic protein that kills sensitive Escherichia coli cells by forming a pore in their phospholipid membrane. The RMS deviation between the C-alpha atoms after the structural alignment is 2.39 Angstrom for the 52 superimposed residues. In the alignment, uteroglobin helices 1, 2, 3, and 4 align with colicin A helices 6, 7, 3, and 4, respectively. The motif is strongly amphipathic in both proteins. On the basis of this common structural motif and of known experimental data on both proteins, we propose that UG binds to the membrane surface by lying on it monotopically. The phospholipase A(2) inhibition would follow this initial binding step. C1 NCI,NIH,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. OI De la Cruz Montserrat, Fco. Xavier/0000-0002-9738-8472 NR 39 TC 8 Z9 8 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD MAY PY 1996 VL 5 IS 5 BP 857 EP 861 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UH925 UT WOS:A1996UH92500007 PM 8732757 ER PT J AU Gronenborn, AM Clore, GM AF Gronenborn, AM Clore, GM TI Rapid screening for structural integrity of expressed proteins by heteronuclear NMR spectroscopy (vol 5, pg 175, 1996) SO PROTEIN SCIENCE LA English DT Correction, Addition RP Gronenborn, AM (reprint author), NIDDKD,NIH,PHYS CHEM LAB,BETHESDA,MD 20892, USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 1 TC 1 Z9 1 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD MAY PY 1996 VL 5 IS 5 BP 981 EP 981 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UH925 UT WOS:A1996UH92500022 ER PT J AU Dixon, DM McNeil, MM Cohen, ML Gellin, BG LaMontagne, JR AF Dixon, DM McNeil, MM Cohen, ML Gellin, BG LaMontagne, JR TI Fungal infections - A growing threat SO PUBLIC HEALTH REPORTS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INVASIVE ASPERGILLOSIS; PNEUMOCYSTIS-CARINII; COCCIDIOIDOMYCOSIS; TRANSPLANTATION; SPOROTRICHOSIS; HISTOPLASMOSIS; EPIDEMIOLOGY; MORTALITY; PATHOGENS AB THE EMERGENCE OF newly identified fungal pathogens and the reemergence of previously uncommon fungal diseases is primarily related to increases in the numbers of susceptible persons: people with HIV infection, bone marrow and organ transplant recipients, cancer patients being treated with chemotherapy, critically ill persons, and very low birth weight (less than or equal to 1500 g) infants. These immunocompromised populations are at risk for infection not only with opportunistic pathogens (for example, Pneumocystis, Candida, Cryptococcus, Trichosporon, Malassezia, Aspergillus, Penicillium mameffei, and numerous other moulds or yeasts) but also with fungal pathogens that usually infect otherwise healthy persons not previously exposed to endemic fungi (for example, Coccidioides immitis, Histoplasma capsulatum, and Blastomyces dermatitidis) and Sporothrix schenckii. Morbidity, mortality, and health care costs associated with fungal infections are high. Addressing the emergence of fungal diseases will require increased surveillance coupled with the availability of rapid, noninvasive diagnostic tests; monitoring the development of resistance to antifungal agents: and research focused on the understanding, prevention, and control of fungal infections. C1 NIAID,CLIN & REGULATORY AFFAIRS BRANCH,NIH,BETHESDA,MD 20892. NIAID,DIV MICROBIOL & INFECT DIS,NIH,BACTERIOL & MYCOL BRANCH,BETHESDA,MD 20892. CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,EMERGING BACTERIAL & MYCOT DIS BRANCH,ATLANTA,GA 30341. RI Andrade, Hugo/M-6631-2013 OI Andrade, Hugo/0000-0001-6781-6125 NR 71 TC 95 Z9 101 U1 3 U2 7 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD MAY-JUN PY 1996 VL 111 IS 3 BP 226 EP 235 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UL149 UT WOS:A1996UL14900022 PM 8643813 ER PT J AU Neta, R Keller, JR Ali, N Blanchette, F Dubois, CM AF Neta, R Keller, JR Ali, N Blanchette, F Dubois, CM TI Contrasting mechanisms of the myeloprotective effects of interleukin-1 against ionizing radiation and cytotoxic 5-fluorouracil SO RADIATION RESEARCH LA English DT Article ID GROWTH-FACTOR-BETA; COLONY-STIMULATING FACTOR; IL-1 RECEPTOR EXPRESSION; TUMOR-NECROSIS-FACTOR; BONE-MARROW CELLS; GRANULOCYTE-MACROPHAGE; HEMATOPOIETIC PROGENITORS; INVIVO; MICE; FIBROBLASTS AB Pretreatment with a single dose of interleukin-1 (IL-1) counteracts the myelosuppressive effects of radiation. In contrast, multiple doses are required to protect against several cytoablative drugs, suggesting different mechanisms. We examined the possibility that myeloprotection is due to IL-1-induced cycling of primitive progenitor cells. First, we evaluated the effect of the time between administration of IL-1 and 5-fluorouracil (5-FU), which kills cycling cells but spares quiescent early progenitors, on their interaction. Pretreatment with a single dose of IL-1 resulted in the death of mice treated with 5-FU provided IL-1 was given 18 h, but not 4 or 48 h, prior to administration of sublethal doses of 5-FU. Second, evaluation of primitive hematopoietic progenitor cells, 13-day spleen colony-forming units (CFU-S) and CFU with high proliferative potential revealed that treatment with 5-FU 18 h after administration of IL-1 results in reduction of CFU-S by 98%, and of CFU with high proliferative potential by 65%, but only a 7 and 10% reduction, respectively, at 48 h. Third, in contrast to protection from death by pretreatment with a single dose of IL-1 at 24 h, two injections of IL-1 at 72 and 24 h before irradiation abrogated such protection. Similarly, the toxicity of 5-FU to progenitor cells was reduced when two injections of IL-1 were administered 48 h apart. This correlates with the time of up-regulation in the bone marrow cells of TGF-beta. These findings suggest that, depending on the schedule of treatment, administration of IL-1 may result in cycling of primitive progenitors, to protect against radiation, and may cause inhibition of cycling to protect against chemotherapeutic drugs. (C) 1996 by Radiation Research Society C1 ARMED FORCES RADIOBIOL RES INST,BETHESDA,MD 20889. NCI,FREDERICK CANC RES & DEV CTR,HEMATOPOIESIS & CYTOKINE DEV SECT,FREDERICK,MD 21702. UNIV SHERBROOKE,FAC MED,DIV IMMUNOL,SHERBROOKE,PQ J1H 5N4,CANADA. NR 48 TC 15 Z9 16 U1 0 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD MAY PY 1996 VL 145 IS 5 BP 624 EP 631 DI 10.2307/3579282 PG 8 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA UH191 UT WOS:A1996UH19100013 PM 8619029 ER PT J AU Kempner, ES AF Kempner, ES TI A critical analysis of the use of radiation inactivation to measure the mass of protein - Comments SO RADIATION RESEARCH LA English DT Letter RP Kempner, ES (reprint author), NATL INST HLTH,PUBL HLTH SERV,DEPT HLTH & HUMAN SERV,BETHESDA,MD 20892, USA. NR 12 TC 1 Z9 1 U1 0 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD MAY PY 1996 VL 145 IS 5 BP 649 EP 650 DI 10.2307/3579290 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA UH191 UT WOS:A1996UH19100021 PM 8619036 ER PT J AU Seed, J Chapin, RE Clegg, ED Dostal, LA Foote, RH Hurtt, ME Klinefelter, GR Makris, SL Perreault, SD Schrader, S Seyler, D Sprando, R Treinen, KA Veeramachaneni, DNR Wise, LD AF Seed, J Chapin, RE Clegg, ED Dostal, LA Foote, RH Hurtt, ME Klinefelter, GR Makris, SL Perreault, SD Schrader, S Seyler, D Sprando, R Treinen, KA Veeramachaneni, DNR Wise, LD TI Methods for assessing sperm motility, morphology, and counts in the rat, rabbit, and dog: A consensus report SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE methods; sperm motility; sperm morphology; sperm counts; rat; rabbit; dog ID ETHANE DIMETHANESULFONATE; ADULT-RATS; FERTILITY; INVITRO AB Reproductive toxicity studies are increasingly including assessments of sperm parameters including motility, morphology, and counts, While these assessments can provide valuable information for the determination of potential reproductive toxicity, the methods for conducting the assessments have not been well developed in all laboratories and are continually evolving, The use of different methods in different laboratories makes comparison of data among laboratories difficult, To address the differences in methods, a working group was convened to discuss methods currently in use, share data, and try to reach consensus about optimal methods for assessing sperm parameters in rats, rabbits, and dogs, This article presents the consensus report, as well as future research needs, with the hope that optimized common methods will aid in the detection of reproductive effects and enhance interlaboratory comparisons. C1 NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. US EPA,WASHINGTON,DC 20460. CORNELL UNIV,ITHACA,NY 14853. WARNER LAMBERT PARKE DAVIS,PARKE DAVIS PHARMACEUT RES,ANN ARBOR,MI 48105. DUPONT CO INC,NEWARK,DE 19714. NIOSH,CINCINNATI,OH 45226. ELI LILLY & CO,LILLY RES LABS,GREENFIELD,IN 46140. US FDA,BELTSVILLE,MD. COLORADO STATE UNIV,FT COLLINS,CO 80523. MERCK RES LABS,W POINT,PA. RP Seed, J (reprint author), ILSI RISK SCI INST,1126 16TH ST NW,WASHINGTON,DC 20036, USA. RI Schrader, Steven/E-8120-2011; OI Chapin, Robert/0000-0002-5997-1261 NR 30 TC 139 Z9 144 U1 1 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD MAY-JUN PY 1996 VL 10 IS 3 BP 237 EP 244 DI 10.1016/0890-6238(96)00028-7 PG 8 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA UN191 UT WOS:A1996UN19100011 PM 8738562 ER PT J AU Baker, I Masserano, J Wyatt, RJ AF Baker, I Masserano, J Wyatt, RJ TI Serum cytokine concentrations in patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE interleukin-1 beta; interleukin-6; tumor necrosis factor-alpha; sIL-2r; cytokines; schizophrenia ID SOLUBLE INTERLEUKIN-2 RECEPTORS; AUTOIMMUNITY AB Interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha and the soluble interleukin-2 receptor were measured in the serum of 34 healthy controls and 48 patients with chronic schizophrenia using ELISA sandwich assays. No differences were found between the controls and patients. RP Baker, I (reprint author), NIMH,NEUROPSYCHIAT BRANCH,NIH,NEUROSCI CTR ST ELIZABETHS,WASHINGTON,DC 20032, USA. NR 24 TC 57 Z9 58 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 1996 VL 20 IS 1-2 BP 199 EP 203 DI 10.1016/0920-9964(95)00089-5 PG 5 WC Psychiatry SC Psychiatry GA UR721 UT WOS:A1996UR72100023 PM 8794510 ER PT J AU Prell, GD Green, JP Elkashef, AM Khandelwal, JK Linnoila, M Wyatt, RJ Lawson, WB Jaeger, AC Kaufmann, CA Kirch, DG AF Prell, GD Green, JP Elkashef, AM Khandelwal, JK Linnoila, M Wyatt, RJ Lawson, WB Jaeger, AC Kaufmann, CA Kirch, DG TI The relationship between urine excretion and biogenic amines and their metabolites in cerebrospinal fluid of schizophrenic patients SO SCHIZOPHRENIA RESEARCH LA English DT Article DE polyuria; polydipsia; cerebrospinal fluid; biogenic amines; histamine; metabolites ID HISTAMINE-N-METHYLTRANSFERASE; PSYCHIATRIC-PATIENTS; DRINKING BEHAVIOR; NOREPINEPHRINE METABOLISM; PARAVENTRICULAR NUCLEUS; CONCENTRATION GRADIENTS; SUPRAOPTIC NUCLEUS; WATER-INTOXICATION; BRAIN HISTAMINE; CONSCIOUS RAT AB Concentrations of norepinephrine and metabolites of biogenic amines were measured in lumbar cerebrospinal fluid of 30 patients with chronic schizophrenia, nine of whom were polyuric. The mean level of norepinephrine was two-fold higher (p less than or equal to 0.025) in polyuric patients than in patients whose excretion of urine was within the normal range. CSF levels of histamine's primary metabolite, tele-methylhistamine, an index of brain histaminergic activity, were positively correlated (p<0.005) with daily urine volume. These results are consistent with the known in influence of norepinephrine and histamine on fluid regulation and suggest that norepinephrine and histamine may be involved in psychogenic polydipsia-polyuria in schizophrenic patients. C1 ST ELIZABETH HOSP,NIMH,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. NIAAA,DIV INTRAMURAL CLIN & BIOL RES,BETHESDA,MD 20205. RP Prell, GD (reprint author), CUNY MT SINAI SCH MED,DEPT PHARMACOL,BOX 1215,1 GUSTAVE LEVY PL,NEW YORK,NY 10029, USA. OI Lawson, William/0000-0002-9324-7090 FU NIDA NIH HHS [5-T32-DA-07135]; NIMH NIH HHS [MH-31805]; NINDS NIH HHS [NS-28012] NR 58 TC 4 Z9 4 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 1996 VL 19 IS 2-3 BP 171 EP 176 DI 10.1016/0920-9964(96)88524-0 PG 6 WC Psychiatry SC Psychiatry GA UP873 UT WOS:A1996UP87300010 PM 8789915 ER PT J AU AnderssonEllstrom, A Dillner, J Hagmar, B Schiller, J Sapp, M Forssman, L Milsom, I AF AnderssonEllstrom, A Dillner, J Hagmar, B Schiller, J Sapp, M Forssman, L Milsom, I TI Comparison of development of serum antibodies to HPV16 and HPV33 and acquisition of cervical HPV DNA among sexually experienced and virginal young girls - A longitudinal cohort study SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID HUMAN PAPILLOMAVIRUS INFECTION; INTRAEPITHELIAL NEOPLASIA; RISK-FACTORS; WOMEN; DETERMINANTS; PREVALENCE; CANCER; ADULTS AB Objectives: To study the importance of sexual activity and early coitus debut on the risk for acquiring infection with human papillomavirus (HPV) type 16 or 33. Study Design: Ninety-eight healthy adolescent girls were followed up with consecutive interviews and donations of serum and cervical brush samples during 2 years. Results: Fourteen percent of sexually experienced girls had serum immunoglobulin G to HPV16 and/or HPV33 capsids, and 14% also had cervical HPV16 or HPV33 DNA. Seropositivity for HPV correlated with detection of cervical HPV DNA. None of the 36 girls without coital experience was seropositive or harbored cervical HPV DNA, Seropositivity for HPV was correlated strongly with the number of sexual partners: Odds ratio for >1 sexual partner was 16.3 (P < 0.001), and for early coitus debut (younger than 17 years of age), it was 14.3 (P < 0.002). Conclusions: Both HPV serology and HPV DNA testing indicated that the number of sexual partners and earliness of coitus debut determined the risk for acquiring HPV infection and that nonsexually transmitted infections are rare or nonexistent among adolescent girls. C1 CTR PUBL HLTH RES,KARLSTAD,SWEDEN. DIST HLTH CTR GRIPEN,KARLSTAD,SWEDEN. KAROLINSKA INST,CTR MICROBIOL & TUMOR BIOL,STOCKHOLM,SWEDEN. OSLO UNIV HOSP,DEPT CLIN CYTOL,OSLO,NORWAY. NIH,CELLULAR ONCOL LAB,BETHESDA,MD 20892. UNIV MAINZ,DEPT MED MICROBIOL,W-6500 MAINZ,GERMANY. UNIV HOSP OSTRA SJUKHUSET,DEPT OBSTET & GYNECOL,GOTHENBURG,SWEDEN. NR 32 TC 76 Z9 77 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD MAY-JUN PY 1996 VL 23 IS 3 BP 234 EP 238 DI 10.1097/00007435-199605000-00013 PG 5 WC Infectious Diseases SC Infectious Diseases GA UM482 UT WOS:A1996UM48200013 PM 8724515 ER PT J AU Soderfeldt, B Soderfeldt, M Muntaner, C OCampo, P Warg, LE Ohlson, CG AF Soderfeldt, B Soderfeldt, M Muntaner, C OCampo, P Warg, LE Ohlson, CG TI Psychosocial work environment in human service organizations: A conceptual analysis and development of the demand-control model SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE demand control model; human service organizations; conceptual analysis ID JOB DECISION LATITUDE; STRESS; HEALTH; PHYSICIANS; STRAIN AB This paper concerns two models that were introduced in two different research domains during the 1970's. The first model regards human service organizations (HSO) as a specific type of organization. The second model, the demand-control model (DC model), concerns the joint effects of job demands and job control on worker health. In the HSO model, there are analyses of the content of jobs, considering the specific characteristics of HSOs, but little is said about the health effects of such work. Those effects stand in focus in the demand-control model. The aim of this paper is to analyze the relevance of the DC model for human service organizations. The paper argues that the object of human service work-the client relation-makes a difference for demand and control in the job. Demand is analyzed into work load, emotional demands and role conflict. Control is divided into administrative control, outcome control, choice of skills, closeness of supervision, control within and over a situation and ideological control. The conclusion is that in applications on HSOs, the basic concepts of the DC model must be developed. Copyright (C) 1996 Elsevier Science Ltd C1 KAROLINSKA INST,DEPT INT HLTH & SOCIAL MED,STOCKHOLM,SWEDEN. LUND UNIV,SCH SOCIAL WORK,S-22100 LUND,SWEDEN. OREBRO MED CTR HOSP,DEPT ENVIRONM & OCCUPAT MED,S-70185 OREBRO,SWEDEN. NIMH,LAB SOCIOENVIRONM STUDIES,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MATERNAL & CHILD HLTH,BALTIMORE,MD. RP Soderfeldt, B (reprint author), OREBRO CTY COUNCIL,BOX 1613,S-70116 OREBRO,SWEDEN. RI Muntaner, C/A-5043-2010 NR 50 TC 57 Z9 58 U1 0 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD MAY PY 1996 VL 42 IS 9 BP 1217 EP 1226 DI 10.1016/0277-9536(95)00231-6 PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA UH965 UT WOS:A1996UH96500002 PM 8733192 ER PT J AU Brocke, S Piercy, C Steinman, L AF Brocke, S Piercy, C Steinman, L TI Superantigens in demyelinating disease SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; STAPHYLOCOCCAL ENTEROTOXIN-B; MYELIN BASIC-PROTEIN; BACTERIAL SUPERANTIGEN; MICE C1 STANFORD UNIV,MED CTR,BECKMAN CTR MOL & GENET MED,DEPT NEUROL & NEUROL SCI,STANFORD,CA 94305. RP Brocke, S (reprint author), NINCDS,NIH,BLDG 10,ROOM 5B-16,10 CTR DR MSC 1400,BETHESDA,MD 20892, USA. NR 25 TC 2 Z9 4 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PD MAY PY 1996 VL 18 IS 1 BP 51 EP 56 DI 10.1007/BF00792608 PG 6 WC Immunology; Pathology SC Immunology; Pathology GA UQ049 UT WOS:A1996UQ04900004 PM 8984679 ER PT J AU Schwartz, GN Warren, MK Sakano, K Szabo, JM Kessler, SW Pashapour, A Gress, RE Perdue, JF AF Schwartz, GN Warren, MK Sakano, K Szabo, JM Kessler, SW Pashapour, A Gress, RE Perdue, JF TI Comparative effects of insulin-like growth factor II (IGF-II) and IGF-II mutants specific for IGF-II/CIM6-P or IGF-I receptors on in vitro hematopoiesis SO STEM CELLS LA English DT Article DE colony-forming units for granulocytes-macrophages (CFU-GM); burst-forming units-erythroid (BFU-E); insulin-like growth factor II (IGF-II); megakaryocyte; interleukin 3; c-kit ligand ID MANNOSE 6-PHOSPHATE RECEPTOR; COLONY-STIMULATING FACTORS; HUMAN-BONE MARROW; FORMING CELLS; FETAL; INTERLEUKIN-3; PROGENITORS; INVITRO; CULTURE; SERUM AB This report presents the results of studies investigating the effect of insulin-like growth factor II (IGF-II) on the proliferation and differentiation of CD34(+) bone marrow cells in serum-substituted liquid cultures, Bone marrow cells were enriched for CD34(+). cells and then placed in liquid cultures supplemented with either interleukin 3 (IL-3) or IL-3 and c-kit ligand with and without the addition of IGF-II. When CD34(+) cells were incubated with IL-3, cellularity increased through-out four weeks of culture. Cellularity was twofold greater when cultures also contained IGF-II. IGF-II also promoted an increase in cellularity in cultures with IL-3 and c-kit ligand, In combination with IL-3 or IL-3 and c-kit ligand, IGF-II promoted an earlier differentiation of granulocytes, as well as an increase in the number of megakaryocyte lineage cells. There were approximately twofold more colony-forming units for granulocytes and macrophages (CFU-GM) and burst-forming units for erythroid cells (BFU-E) in cultures containing both IL-3 and IGF-II than in cultures with IL-3 alone. These results demonstrate that in cytokine-supplemented media, physiological concentrations of IGF-II augmented both the proliferation and differentiation of CD34(+) bone marrow cells while maintaining a greater number of progenitor cells. To identify the receptors through which IGF-II enhances in vitro hematopoiesis, IGF-II was substituted with one of the mutant forms of IGF-II that selectively interacts with either IGF-II/CIM6-P receptors or with IGF-I and insulin receptors. The results with the mutant forms of IGF-II demonstrate that IGF-II augments in vitro hematopoiesis primarily through Its interaction with IGF-I and possibly insulin receptors, rather than IGF-II/CIM6-P receptors. C1 OTSUKA AMER PHARMACEUT CO, ROCKVILLE, MD USA. DAIICHI PHARMACEUT CO LTD, MOL BIOL RES LAB, TOKYO, JAPAN. NATL NAVAL MED CTR, IMMUNE CELL BIOL PROGRAM, BETHESDA, MD 20814 USA. AMER RED CROSS, HOLLAND LAB, MOLEC BIOL LAB, ROCKVILLE, MD USA. RP Schwartz, GN (reprint author), NCI, MED BRANCH,TRANSPLANTAT THERAPY SECT,NIH,BLDG 10, ROOM 12N226, BETHESDA, MD 20892 USA. NR 38 TC 19 Z9 19 U1 0 U2 0 PU ALPHAMED PRESS PI DAYTON PA 4100 S KETTERING BLVD, DAYTON, OH 45439-2092 SN 1066-5099 J9 STEM CELLS JI Stem Cells PD MAY PY 1996 VL 14 IS 3 BP 337 EP 350 PG 14 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA UM632 UT WOS:A1996UM63200009 PM 8724700 ER PT J AU Abbott, RD Curb, JD Rodriguez, BL Sharp, DS Burchfiel, CM Yano, K AF Abbott, RD Curb, JD Rodriguez, BL Sharp, DS Burchfiel, CM Yano, K TI Effect of dietary calcium and milk consumption on risk of thromboembolic stroke in older middle-aged men - The Honolulu Heart Program SO STROKE LA English DT Article DE calcium; diet; risk factors; stroke outcome ID BLOOD-PRESSURE; PHYSICAL-ACTIVITY; JAPANESE MEN; NUTRIENT INTAKE; DISEASE; HAWAII; SUPPLEMENTATION; HYPERTENSION; CALIFORNIA; ALCOHOL AB Background and Purpose Evidence suggests that dietary calcium is protective against hypertension. This report examines whether the effect has an influence on thromboembolic stroke. Methods Since 1965, the Honolulu Heart Program has followed a cohort of men in a study of cardiovascular disease. This report examines the effect of baseline dietary calcium and milk intake on stroke risk in 22 years of follow-up in 3150 older middle-aged men (55 to 68 years). Results Men who were nondrinkers of milk experienced stroke at twice the rate (P<.05) of men who consumed 16 oz/d or more (7.9 versus 3.7 per 100, respectively). While the rare of stroke decreased with increasing milk intake (P<.05), the decline in stroke risk with increased consumption was modest for those who consumed under 16 oz/d. Intake of dietary calcium was also associated with a reduced risk of stroke (P<.01), although its association was confounded with milk consumption. Calcium intake from nondairy sources was not related to stroke, suggesting that other constituents or covariates related to milk consumption may be important. Conclusions We conclude that an association bi tween milk consumption and a reduced risk of stroke in older middle-aged men cannot be explained by intake of dietary calcium. Since milk is often part of a diverse pattern of dietary intake, it is difficult to determine whether milk consumption has a direct role in reducing the risk of stroke. Data suggest that consumption of milk in older middle age is not harmful, and when combined with a balanced diet, weight control, and physical activity, reductions in the risk of stroke may occur. C1 KUAKINI MED CTR,HONOLULU HEART PROGRAM,HONOLULU,HI. UNIV HAWAII MANOA,JOHN A BURNS SCH MED,DEPT MED,HONOLULU,HI 96822. NHLBI,EPIDEMIOL & BIOMETRY PROGRAM,HONOLULU EPIDEMIOL RES SECT,HONOLULU,HI. RP Abbott, RD (reprint author), UNIV VIRGINIA,SCH MED,DIV BIOSTAT,BOX 432,CHARLOTTESVILLE,VA 22908, USA. FU NHLBI NIH HHS [N01-HC-05102] NR 36 TC 100 Z9 100 U1 1 U2 9 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 1996 VL 27 IS 5 BP 813 EP 818 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA UJ685 UT WOS:A1996UJ68500003 PM 8623098 ER PT J AU Curb, JD Abbott, RD MacLean, CJ Rodriguez, BL Burchfiel, CM Sharp, DS Ross, GW Yano, K AF Curb, JD Abbott, RD MacLean, CJ Rodriguez, BL Burchfiel, CM Sharp, DS Ross, GW Yano, K TI Age-related changes in stroke risk in men with hypertension and normal blood pressure SO STROKE LA English DT Article DE elderly; hypertension; risk factors; stroke ID CORONARY HEART-DISEASE; JAPANESE MEN; MORTALITY; HAWAII; FRAMINGHAM; INFARCTION; PROGRAM; ASSOCIATION; CALIFORNIA; SURVIVAL AB Background and Purpose Stroke is a major contributor to total morbidity and mortality in older individuals, and hypertension is an important risk factor for stroke. Relatively few data exist on whether this relationship changes with age. Methods To examine age-related changes in the relation ships between risk of stroke and hypertension, we examined the 6-year incidence of stroke among men aged 45 to 81 years using updated blood pressure data from three examinations of Japanese-American men from the Honolulu Heart Program. Results Both the prevalence of hypertension (systolic blood pressure greater than or equal to 160 mm Hg or diastolic blood pressure greater than or equal to 95 mm Hg or the use of antihypertensive medication) and the 6-year incidence of stroke increased significantly with increasing age (P<.01). The increase In thromboembolic stroke incidence with age was more marked in those who were normotensive at baseline (2.7/1000 in those aged 45 to 54 years to 23.9/1000 in those greater than or equal to 65 years; P<.001) than in hypertensive men (20.6/1000 in those aged 45 to 54 years to 33.5/1000 in those greater than or equal to 65 years; P<.01). The age-related increase in risk of thromboembolic stroke among normotensive men resulted in a decrease in the percentage of strokes attributable to hypertension (50% in those aged 45 to 54 years to 18% in those greater than or equal to 65 years; P<.05). Similar trends were seen for hemorrhagic stroke. There were no age-related changes in the relationships of other major atherosclerotic risk factors with stroke. The hypertension/stroke relationships were present after multivariate adjustment for age, smoking, cholesterol, and other factors. Conclusions In view of the greater prevalence of hypertension and the proven efficacy of treatment in the elderly, these findings do not negate the value of aggressive screening and treatment of hypertension in this age group. However, it appears that other unidentified factors have an increasing role in the causation of stroke with advancing age. C1 KUAKINI MED CTR,HONOLULU HEART PROGRAM,HONOLULU,HI. HAWAII DEPT VET AFFAIRS,HONOLULU,HI. UNIV VIRGINIA,SCH MED,DIV BIOSTAT,CHARLOTTESVILLE,VA 22903. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PSYCHIAT,RICHMOND,VA 23298. NHLBI,BETHESDA,MD 20892. RP Curb, JD (reprint author), UNIV HAWAII,JOHN A BURNS SCH MED,DEPT MED,DIV CLIN EPIDEMIOL,347 N KUAKINI ST,HONOLULU,HI 96817, USA. FU NHLBI NIH HHS [N01-HC-05102] NR 37 TC 42 Z9 43 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 1996 VL 27 IS 5 BP 819 EP 824 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA UJ685 UT WOS:A1996UJ68500004 PM 8623099 ER PT J AU Li, RM Newcomer, SE AF Li, RM Newcomer, SE TI The exclusion of never-married women from Chinese fertility surveys SO STUDIES IN FAMILY PLANNING LA English DT Article; Proceedings Paper CT 2nd International Symposium on Fertility Regulation CY MAY 21-25, 1995 CL BEIJING, PEOPLES R CHINA ID SEXUAL-BEHAVIOR; UNITED-STATES; ABORTION; TAIWAN AB Never-married women have been regularly excluded in official national surveys of fertility in China, even in light of evidence of increasing premarital sexual activity. Likewise, never-married women in the United States were consistently excluded from national fertility surveys prior to 1982 because of the perceived sensitivity of questions about contraceptive use and sexual activities. Data on sexual fertility behavior from all women of reproductive age, regardless of marital status, can provide direct measures of sexual activity and unintended pregnancies, as well as facilitate modeling of social networks underlying the sexual transmission of diseases. China's need for such information, however sensitive, will become more difficult to ignore given increasing pressures to attend to the health needs of their never-married but sexually active population. RP Li, RM (reprint author), NICHHD,POPULAT RES CTR,NIH,6100 EXECUT BLVD,ROOM 8B13,BETHESDA,MD 20892, USA. NR 47 TC 3 Z9 3 U1 0 U2 0 PU POPULATION COUNC PI NEW YORK PA ONE DAG HAMMARSKJOLD PLAZA, NEW YORK, NY 10017 SN 0039-3665 J9 STUD FAMILY PLANN JI Stud. Fam. Plan. PD MAY-JUN PY 1996 VL 27 IS 3 BP 148 EP 154 DI 10.2307/2137920 PG 7 WC Demography; Public, Environmental & Occupational Health SC Demography; Public, Environmental & Occupational Health GA UX675 UT WOS:A1996UX67500003 PM 8829297 ER PT J AU Zenilman, ME Perfetti, R Swinson, K Magnuson, T Shuldiner, AR AF Zenilman, ME Perfetti, R Swinson, K Magnuson, T Shuldiner, AR TI Pancreatic regeneration (reg) gene expression in a rat model of islet hyperplasia SO SURGERY LA English DT Article ID CHRONIC CALCIFYING PANCREATITIS; PROTEIN MESSENGER-RNA; ENDOCRINE PANCREAS; CELL; INDUCTION; EXOCRINE; SEQUENCE; HAMSTER; NESIDIOBLASTOSIS; STIMULATION AB Background. After pancreatectomy, regeneration of acinar and islet elements occurs. Recent data from a model of islet hyperplasia in the hamster suggested that induction of a local pancreatic factor stimulates islet formation. We postulate that the reg gene may be this factor. Methods. We studied reg expression during induction of islet growth by using a similar model in the rat. Rats underwent surgical wrapping of the splenic lobe of the pancreas or shan operation. Results. At 2 days ductular proliferation and immunohistochemical evidence of insulin within ductular epithelia were evident in the wrapped lobe. By 14 and 56 days islet number per square millimeter increased 63% and 43%, respectively. Reg mRNA levels, measured by Northern blot analysis with a rat reg cDNA probe (n = 5), increased 300% at 2 days in the wrapped robe and decreased to that of unwrapped controls by 14 days. In situ hybridization showed localization of reg to the acinar cells. In unwrapped gastric lobes of animals who underwent surgical wrapping of the splenic lobe, no change in islet number per square millimeter or reg gene expression was noted. Conclusions. Surgical wrapping of the pancreatic splenic lobe induces local reg gene expression that is temporally associated with duct cell hyperplasia. This is followed by islet formation within the wrapped lobe. Reg may play a role in the induction of new islets from ductular precursors and in maintenance of normal islet function. C1 JOHNS HOPKINS UNIV, SCH MED, DEPT SURG, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT MED, BALTIMORE, MD 21205 USA. NIA, NIH, LAB CLIN PHYSIOL, BALTIMORE, MD 21224 USA. NR 39 TC 34 Z9 34 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAY PY 1996 VL 119 IS 5 BP 576 EP 584 DI 10.1016/S0039-6060(96)80270-4 PG 9 WC Surgery SC Surgery GA UJ836 UT WOS:A1996UJ83600017 PM 8619215 ER PT J AU Rauhala, P Mohanakumar, KP Sziraki, I Lin, AMY Chiueh, CC AF Rauhala, P Mohanakumar, KP Sziraki, I Lin, AMY Chiueh, CC TI S-nitrosothiols and nitric oxide, but not sodium nitroprusside, protect nigrostriatal dopamine neurons against iron-induced oxidative stress in vivo SO SYNAPSE LA English DT Article DE nitric oxide; lipid peroxidation; ferrous citrate; free radical; S-nitrosothiols AB Intranigral infusion of ferrous citrate (4.2 nmol) induced an acute lipid peroxidation in the substantia nigra and a chronic dopamine depletion in the striatum of rat nigrostriatal system. Coinfusion of 8.4 nmol nitric oxide donors such as S-nitroso-glutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP) or nitric oxide (similar to 2 nmol) protected nigrostriatal neurons against iron-induced lipid peroxidation and associated oxidative injury. However, sodium nitroprusside (SNP, 8.4 nmol) augmented dopamine depletion caused by ferrous citrate because SNP is a ferricyanide complex. The present in vivo results indicate that nitric oxide and S-nitrosothiols are antioxidants which can protect brain dopamine neurons against oxidant stress/damage. (C) 1996 Wiley-Liss, Inc. RP Rauhala, P (reprint author), NIMH,NIH,UNIT NEUROTOXICOL & NEUROPROT,CLIN SCI LAB,BETHESDA,MD 20892, USA. OI Rauhala, Pekka/0000-0003-2036-3522 NR 17 TC 80 Z9 81 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD MAY PY 1996 VL 23 IS 1 BP 58 EP 60 DI 10.1002/(SICI)1098-2396(199605)23:1<58::AID-SYN7>3.0.CO;2-G PG 3 WC Neurosciences SC Neurosciences & Neurology GA UH322 UT WOS:A1996UH32200007 PM 8723136 ER PT J AU Ye, B Otaka, A Burke, TR AF Ye, B Otaka, A Burke, TR TI Preparation of N-alpha-Boc 4-O-diethylphospho-L-azatyrosine, a reagent potentially useful for the synthesis of signal transduction related peptides SO SYNLETT LA English DT Article DE azatyrosine; phosphotyrosine; signal transduction; SH2 domain ID SERINE; ACIDS AB Preparation of the phosphorylated azatyrosine analogue, 2(S)-Na-Boc-3-[5'-(diethyl phosphoryloxy)-2'-pyridyl]propionate (3), is reported. This compound is designed for the solid-phase synthesis of cell signal transduction peptides containing a phosphotyrosyl reside bearing a nitrogen atom in the tyrosyl aromatic ring. An important aspect of the synthetic approach is the use of diethyl phosphate functionality for phenolic hydroxyl protection during palladium-mediated coupling. C1 NCI,MED CHEM LAB,DIV BASIC SCI,NATL INST HLTH,BETHESDA,MD 20892. KYOTO UNIV,FAC PHARMACEUT SCI,SAKYO KU,KYOTO 606,JAPAN. RI Burke, Terrence/N-2601-2014 NR 13 TC 10 Z9 10 U1 0 U2 0 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0936-5214 J9 SYNLETT JI Synlett PD MAY PY 1996 IS 5 BP 459 EP & PG 3 WC Chemistry, Organic SC Chemistry GA UL334 UT WOS:A1996UL33400018 ER PT J AU Vaisman, B AF Vaisman, B TI Untitled SO TERATOLOGY LA English DT Letter ID NECROSIS-FACTOR-ALPHA; ASCORBIC-ACID; THALIDOMIDE; BRAIN RP Vaisman, B (reprint author), NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892, USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0040-3709 J9 TERATOLOGY JI Teratology PD MAY PY 1996 VL 53 IS 5 BP 283 EP 284 DI 10.1002/(SICI)1096-9926(199605)53:5<283::AID-TERA1>3.0.CO;2-2 PG 2 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA VE896 UT WOS:A1996VE89600002 PM 8879085 ER PT J AU Wyszynski, DF Beaty, TH AF Wyszynski, DF Beaty, TH TI Review of the role of potential teratogens in the origin of human nonsyndromic oral clefts SO TERATOLOGY LA English DT Article ID MATERNAL CIGARETTE-SMOKING; GENE-ENVIRONMENT INTERACTION; CONGENITAL-MALFORMATIONS; BIRTH-DEFECTS; ANTIEPILEPTIC DRUGS; FACIAL CLEFTS; FOLIC-ACID; PERICONCEPTIONAL SUPPLEMENTATION; ANTICONVULSANT DRUGS; EPILEPTIC PATIENTS AB Oral clefts are common birth defects affecting approximately 1 every 1,000 caucasian newborns. While many syndromes with cleft lip with or without cleft palate (CL/P) or with cleft palate (CP) are recognized, the majority of oral clefts fall into the category of ''nonsyndromic oral clefts'' and the etiology of this group remains incompletely understood. Investigators agree that oral clefts are multifactorial in origin, with both genetic and environmental factors in their etiology. While animal models have identified several teratogens for oral clefts, their precise relevance for humans remains unclear. The goal of this work is to review literature on environmental exposures potentially associated with non-syndromic oral clefts. (C) 1996 Wiley-Liss, Inc. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21205. NIH,MED GENET BRANCH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. FU NIDCR NIH HHS [R01-DE10293] NR 98 TC 78 Z9 82 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0040-3709 J9 TERATOLOGY JI Teratology PD MAY PY 1996 VL 53 IS 5 BP 309 EP 317 PG 9 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA VE896 UT WOS:A1996VE89600006 PM 8879089 ER PT J AU Carter, CA Ellington, WW VanBeneden, RJ AF Carter, CA Ellington, WW VanBeneden, RJ TI Confocal laser scanning microscopy of oncogene localization in rainbow trout cell lines derived from normal and tumor tissue SO TOXICOLOGIC PATHOLOGY LA English DT Article DE fish cell lines; oncogene expression; c-myc antibody; pan-ras antibody ID C-MYC; EMBRYO FIBROBLASTS; B6C3F1 MOUSE; RAS GENES; EXPRESSION; FAMILY; CARCINOGENESIS; MESOTHELIOMA; CARCINOMAS; MUTATIONS AB We examined the localization and expression of the nuclear oncoprotein c-myc and the cytoplasmic membrane-associated oncoprotein c-ras in rainbow trout cell lines derived from both normal and tumor tissue in order to question whether c-myc and ras oncoprotein immunostaining was increased in cells derived from tumors compared to cells derived from normal tissue. Cell lines examined were derived from normal rainbow trout gonadal cells (RTG-2), a rainbow trout hepatoma (RTH-149), and a rainbow trout mesothelioma (RTM). Protein products of c-ras and c-myc were visualized in these 3 cell lines by employing fluorescein-labeled anti-mouse pan-ras and c-myc antibodies. The RTG-2 cells were used in this study as normal, control cells, and they exhibited little pan-ras and c-myc staining. The RTH-149 cell line (a tumorigenic cell line) exhibited positive pan-ras staining in regions of the membrane and cell cytoplasm. Localization of c-myc staining to perinuclear regions was punctate in RTH-149 cells. RTM cells (also a tumorigenic cell line) displayed a ms staining localization similar to the pattern seen in RTH-149 cells. RTM cells exhibit a diffuse perinuclear staining and, thus, display a more ubiquitous localization of c-myc than RTH-149 cells. Northern blot analysis indicated that c-myc expression was highest in RTM cells, whereas RTG-2 cells and RTH-149 cells expressed similar lower levels of c-myc expression. We were unable to detect significant ms expression in any of the cell lines by Northern blot analysis. in summary, the cell line derived from normal tissue, the RTG-2 cells, displayed little ras and c-myc immunostaining, whereas the cell lines derived from tumorigenic tissue, RTH and RTM cells, displayed increased immunostaining for c-myc and ras proteins. C1 NIEHS,LAB EXPT PATHOL,RES TRIANGLE PK,NC 27709. RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 38 TC 5 Z9 5 U1 1 U2 1 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAY-JUN PY 1996 VL 24 IS 3 BP 339 EP 345 PG 7 WC Pathology; Toxicology SC Pathology; Toxicology GA UN140 UT WOS:A1996UN14000010 PM 8736390 ER PT J AU Portier, CJ Sherman, CD Kohn, M Edler, L KoppSchneider, A Maronpot, RM Lucier, G AF Portier, CJ Sherman, CD Kohn, M Edler, L KoppSchneider, A Maronpot, RM Lucier, G TI Modeling the number and size of hepatic focal lesions following exposure to 2,3,7,8-TCDD SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID DOSE-RESPONSE RELATIONSHIPS; ENZYME-ALTERED FOCI; RAT-LIVER; QUANTITATIVE-ANALYSIS; TUMOR PROMOTION; RISK ASSESSMENT; 2-STAGE MODEL; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; HEPATOCARCINOGENESIS; CARCINOGENESIS AB Data on the size and number of placental glutathione S-transferase-positive (PGST+) foci were collected from a two-stage hepatocarcinogenesis model in female Sprague-Dawley rats, The study consisted of multiple 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-exposed dose groups including both diethylnitrosomine (DEN)-initiated and uninitiated animals, Groups were observed after 15 or 31 weeks of TCDD exposure. The parameters in the first half of a two-stage mathematical model of carcinogenesis were estimated from these data. If the model is valid, the results suggest that TCDD stimulates the production of PGST+ foci and promotes the growth of PGST+ foci, This finding suggests a complicated mechanism for TCDD-induced production of hepatic foci that we refer to as activation, labeling TCDD as an activator. The analysis also indicates that there is an interaction between DEN and TCDD which results in dose-related formation of initiated cells throughout the study period. Best-fitting curves (using maximum likelihood methods) for TCDD-induced activation and promotion reached saturation levels at low doses of TCDD. In summary, the model fit the data well, but leads to an interpretation of the data which either questions the validity of the model or implies that our understanding of the effects of TCDD and DEN is incomplete. (C) 1996 Academic Press, Inc. C1 NIEHS, LAB EXPTL PATHOL, RES TRIANGLE PK, NC 27709 USA. NIEHS, LAB BIOCHEM RISK ASSESSMENT, RES TRIANGLE PK, NC 27709 USA. DEUTSCH KREBSFORSCHUNGSZENTRUM, D-6900 HEIDELBERG, GERMANY. RP NIEHS, STAT & BIOMATH BRANCH, RES TRIANGLE PK, NC 27709 USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 32 TC 38 Z9 40 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 0041-008X EI 1096-0333 J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAY PY 1996 VL 138 IS 1 BP 20 EP 30 DI 10.1006/taap.1996.0093 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA UK983 UT WOS:A1996UK98300003 PM 8658509 ER PT J AU Zawia, NH Harry, GJ AF Zawia, NH Harry, GJ TI Developmental exposure to lead interferes with glial and neuronal differential gene expression in the rat cerebellum SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID FIBRILLARY ACIDIC PROTEIN; NERVE-GROWTH-FACTOR; MESSENGER-RNA; INTERMEDIATE FILAMENTS; INSITU HYBRIDIZATION; BRAIN; GAP-43; MOUSE; LOCALIZATION; MYELINATION AB Exposure to lead (Pb) has been shown to disrupt developmental processes in the brain and to result in impaired brain function. In these studies, we examined the role of differential gene expression as a possible target site which may partially mediate Pb's neurotoxicity. Animals were lactationally exposed to 0.2% lead acetate from birth to weaning. On postnatal days (PND) 3, 6, 9, 12, 15, 20, 25, 30, 40, and 50, the cerebelli of control and Pb-exposed pups were examined, by Northern blot analysis for changes in the developmental profiles of neuronotypic and gliotypic markers: Growth-associated protein (GAP-43), myelin basic protein (MBP), and glial fibrillary acidic protein (GFAP), while actin was monitored as an indicator of generalized effects on developmental gene expression and exhibited no significant changes following Pb exposure. On PND 9, Pb exposure resulted in a significant stimulation in the expression of the neuronal GAP-43 mRNA. Although Pb induced an early onset of MBP gene expression, the mRNA levels for both MBP and GFAP were decreased between PND 20 and 50, in Pb-exposed animals, These studies suggest that exposure to Pb may selectively interfere with critical developmental gene expression. (C) 1996 Academic Press, Inc. C1 MEHARRY MED COLL,ENVIRONM HLTH DIV,NASHVILLE,TN 37208. NIEHS,BIOCHEM RISK ANAL LAB,RES TRIANGLE PK,NC 27709. RP Zawia, NH (reprint author), MEHARRY MED COLL,DEPT PHARMACOL,1005 DB TODD BLVD,NASHVILLE,TN 37208, USA. NR 43 TC 56 Z9 57 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAY PY 1996 VL 138 IS 1 BP 43 EP 47 DI 10.1006/taap.1996.0095 PG 5 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA UK983 UT WOS:A1996UK98300005 PM 8658511 ER PT J AU Luster, MI AF Luster, MI TI Immunotoxicology: Clinical consequences SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article; Proceedings Paper CT Great-Lakes Human Health Effects Research Symposium CY MAY 04-06, 1994 CL DETROIT, MI SP US Dept Hlth & Human Serv, Public Hlth Serv, Agcy Tox Subst & Dis Registry,, Atlanta, Hlth Canada, Ottawa, Risk Sci Inst, Int Life Sci Inst, Washington ID CHEMICALS C1 NIEHS,NIH,RES TRIANGLE PK,NC 27709. NR 5 TC 5 Z9 5 U1 0 U2 0 PU PRINCETON SCIENTIFIC PUBL INC PI PRINCETON PA PO BOX 2155, PRINCETON, NJ 08543 SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD MAY-AUG PY 1996 VL 12 IS 3-4 BP 533 EP 535 PG 3 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA VA693 UT WOS:A1996VA69300024 PM 8843569 ER PT J AU Rouault, TA Klausner, RD AF Rouault, TA Klausner, RD TI Iron-sulfur clusters as biosensors of oxidants and iron SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID ELEMENT-BINDING-PROTEIN; FE-S CLUSTER; REGULATORY FACTOR; ESCHERICHIA-COLI; RNA-BINDING; ACONITASE; INACTIVATION; BIOSYNTHESIS; SENSITIVITY; CONVERSION AB Iron-sulfur clusters are prosthetic groups commonly found in proteins that participate in oxidation-reduction reactions and catalysis. Here, we focus on two proteins that contain iron-sulfur clusters, the fumarate nitrate reduction (FNR) protein of Escherichia coli and mammalian iron-responsive-element-binding protein 1 (IRP1), both of which function as direct sensors of oxygen and iron levels. Assembly and disassembly of iron-sulfur clusters is the key to sensing in these proteins and we speculate that iron-sulfur clusters might be found in other regulatory proteins that sense levels of iron and/or oxygen. RP Rouault, TA (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. NR 48 TC 207 Z9 208 U1 0 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD MAY PY 1996 VL 21 IS 5 BP 174 EP 177 DI 10.1016/S0968-0004(96)10024-4 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UK185 UT WOS:A1996UK18500006 PM 8871401 ER PT J AU Hengen, PN AF Hengen, PN TI Methods and reagents - Eliminating banding artifacts from SDS-PAGE SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID POLYACRYLAMIDE-GEL-ELECTROPHORESIS; 2-MERCAPTOETHANOL RP Hengen, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 9 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD MAY PY 1996 VL 21 IS 5 BP 191 EP 193 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UK185 UT WOS:A1996UK18500011 PM 8871406 ER PT J AU Crawley, JN AF Crawley, JN TI Unusual behavioral phenotypes of inbred mouse strains - Commentary SO TRENDS IN NEUROSCIENCES LA English DT Article RP Crawley, JN (reprint author), NIMH,SECT BEHAV NEUROPHARMACOL,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892, USA. NR 9 TC 112 Z9 113 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD MAY PY 1996 VL 19 IS 5 BP 181 EP 182 DI 10.1016/S0166-2236(96)20021-9 PG 2 WC Neurosciences SC Neurosciences & Neurology GA UH143 UT WOS:A1996UH14300006 PM 8723201 ER PT J AU Kirnbauer, R Chandrachud, LM ONeil, BW Wagner, ER Grindlay, GJ Armstrong, A McGarvie, GM Schiller, JT Lowy, DR Campo, MS AF Kirnbauer, R Chandrachud, LM ONeil, BW Wagner, ER Grindlay, GJ Armstrong, A McGarvie, GM Schiller, JT Lowy, DR Campo, MS TI Virus-like particles of bovine papillomavirus type 4 in prophylactic and therapeutic immunization SO VIROLOGY LA English DT Article ID COTTONTAIL RABBIT PAPILLOMAVIRUS; L1 PROTEIN; VACCINATION; CELLS; L2; EXPRESSION; INFECTION; INVITRO AB Virus-like particles were produced in insect cells containing either the L1 and L2 capsid proteins of bovine papillomavirus type 4 (BPV-4) or only the L1 protein. Both preparations of VLPs proved to be extremely effective prophylactic vaccines. Thirteen of 15 calves immunised with either L1-L2 VLPs or L1-VLPs were refractory to experimental challenge with high doses of BPV-4 and did not develop papillomas, while 9 of 10 control animals developed multiple oral papillomas. VLPs were not efficient as therapeutic vaccine in calves with established papillomas, although VLP-vaccinated animals appeared to undergo tumour regression more rapidly than nonvaccinated control animals. Antibody responses in VLP-vaccinated calves were associated with prevention of disease but not with regression of papillomas. Thus prophylactic VLP vaccination is effective in preventing disease in this model of mucosal papillomavirus infection. VLPs and native virus share at least some conformational epitopes, as shown by the cross-reactivity of their antibodies. (C) 1996 Academic Press, Inc. C1 BEATSON INST CANC RES,CRC,BEATSON LABS,GLASGOW G61 1BD,LANARK,SCOTLAND. UNIV VIENNA,SCH MED,DEPT DERMATOL,DIV IMMUNOL ALLERGY & INFECT DIS,A-1090 VIENNA,AUSTRIA. UNIV GLASGOW,SCH VET,DEPT VET PATHOL,GLASGOW G61 1BD,LANARK,SCOTLAND. NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. NR 35 TC 203 Z9 211 U1 0 U2 7 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD MAY 1 PY 1996 VL 219 IS 1 BP 37 EP 44 DI 10.1006/viro.1996.0220 PG 8 WC Virology SC Virology GA UJ532 UT WOS:A1996UJ53200005 PM 8623552 ER PT J AU Puri, A Morris, SJ Jones, P Ryan, M Blumenthal, R AF Puri, A Morris, SJ Jones, P Ryan, M Blumenthal, R TI Heat-resistant factors in human erythrocyte membranes mediate CD4-dependent fusion with cells expressing HIV-1 envelope glycoproteins SO VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; INFLUENZA HEMAGGLUTININ; INITIAL-STAGES; CD4-MEDIATED FUSION; HTLV-III/LAV; T4 MOLECULE; HUMAN CD4; INFECTION; RECEPTOR; REQUIREMENTS AB It has been shown that human CD4 expressed in nonhuman cells does not support HIV-1 entry into those cells and that components from human cells in addition to CD4 are required to overcome the block. We have used human red blood cells (huRBC) as a source for the accessory components since their membrane composition is less complex than that of nucleated cells and they are well characterized. Components were transferred by fusion of huRBC to nonhuman CD4(+) cells mediated by influenza hemagglutinin or polyethylene glycol. The RBC-modified nonhuman CD4(+) cells were labeled with fluorescent markers and incubated with gp120-gp41-expressing cells labeled with a different fluorescent probe. Fusion between RBC-modified nonhuman CD4(+) cells and gp120-gp41-expressing cells was quantified by fluorescence video microscopy. Human erythrocyte components transferred to nonhuman CD4(+) cells conferred HIV-1 envelope glycoprotein-mediated fusion susceptibility to those cells. The fusion was enhanced by pretreatment of the erythrocytes for 10 min at 56 degrees. No gp120-gp41-mediated fusion was observed when components from nonhuman RBC were transferred to nonhuman CD4(+) cells. Human cell lines with pre-RBC characteristics (K562-CD4) also supported HIV-1 envelope glycoprotein-mediated fusion. (C) 1996 Academic Press, Inc. C1 NCI,SECT MEMBRANE STRUCT & FUNCT,NIH,BETHESDA,MD 20892. UNIV MISSOURI,DIV MOLEC BIOL & BIOCHEM,SCH BIOL SCI,KANSAS CITY,MO 64110. NR 28 TC 17 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD MAY 1 PY 1996 VL 219 IS 1 BP 262 EP 267 DI 10.1006/viro.1996.0244 PG 6 WC Virology SC Virology GA UJ532 UT WOS:A1996UJ53200029 PM 8623537 ER PT J AU DeWeerd, P Desimone, R Ungerleider, LG AF DeWeerd, P Desimone, R Ungerleider, LG TI Cue-dependent deficits in grating orientation discrimination after V4 lesions in macaques SO VISUAL NEUROSCIENCE LA English DT Article DE macaque; area V4; lesion effects; texture-defined contours; illusory contour ID MONKEY VISUAL-CORTEX; CORTICAL AREA V4; ILLUSORY CONTOURS; FUNCTIONAL-ORGANIZATION; COLOR CONSTANCY; CEREBRAL-CORTEX; ALERT MACAQUE; RHESUS-MONKEY; CONNECTIONS; MT AB To examine the role of visual area V4 in pattern vision, we tested two monkeys with lesions of V4 on tasks that required them to discriminate the orientation of contours defined by several different cues. The cues used to separate the contours from their background included luminance, color, motion, and texture, as well as phase-shifted abutting gratings that created an ''illusory'' contour. The monkeys were trained to maintain fixation on a fixation target while discriminating extrafoveal stimuli, which were located in either a normal control quadrant of the visual field or in a quadrant affected by a lesion of area V4 in one hemisphere. Comparing performance in the two quadrants, we found significant deficits for contours defined by texture and for the illusory contour, but smaller or no deficits for motion-, color-, and luminance-defined contours. The data suggest a specific role of V4 in the perception of illusory contours and contours defined by texture. C1 NIMH,PSYCHOL & PSYCHOPATHOL LAB,BETHESDA,MD 20892. NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. NR 76 TC 66 Z9 66 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0952-5238 J9 VISUAL NEUROSCI JI Visual Neurosci. PD MAY-JUN PY 1996 VL 13 IS 3 BP 529 EP 538 PG 10 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA UH528 UT WOS:A1996UH52800013 PM 8782380 ER PT J AU Seibel, M Baird, P Rhodes, R Bustillo, M Goldhill, F Wallach, EE Strong, C Carr, S AF Seibel, M Baird, P Rhodes, R Bustillo, M Goldhill, F Wallach, EE Strong, C Carr, S TI Session one: Selected international perspectives on the regulation of assisted reproduction - Open discussion SO WOMENS HEALTH ISSUES LA English DT Editorial Material C1 CUNY,MT SINAI SCH MED,NEW YORK,NY 10021. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. UNIV TENNESSEE,CTR HLTH SCI,MEMPHIS,TN 38163. NIH,BETHESDA,MD 20892. RP Seibel, M (reprint author), FAULKNER CTR REPROD MED,BOSTON,MA, 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 SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD MAY-JUN PY 1996 VL 6 IS 3 BP 129 EP 131 PG 3 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA UN922 UT WOS:A1996UN92200004 ER PT J AU Jensen, RT AF Jensen, RT TI CCKB/gastrin receptor antagonists: Recent advances and potential uses in gastric secretory disorders SO YALE JOURNAL OF BIOLOGY AND MEDICINE LA English DT Review ID PANCREATIC-ENZYME SECRETION; ZOLLINGER-ELLISON SYNDROME; CHOLECYSTOKININ-B; GUINEA-PIG; DISTINCT RECEPTORS; ACID-SECRETION; PANIC DISORDER; STREPTOMYCES SP-NR0489; FUNCTIONAL EXPRESSION; PEPSINOGEN SECRETION AB Cholecystokinin (CCK) and the structurally related peptide, gastrin, have numerous effects on tissues in the central nervous system and gastrointestinal tract; Recent studies show these effects are mediated by a CCKA and CCKB receptor. Knowledge of the physiological role and role of CCKB receptors in pathologic processes has been particularly limited by the availability of selective, potent receptor antagonists. Recently, new members of five different classes of;non-peptide CCKB receptor antagonists are reported and are reviewed briefly. These include compounds isolated from Streptomyces (tetronothiodin, virginiamycin analogues), ureido-acetamide analogues (RP 69758, RP 72540, RP 73870), newer benzodiazepine analogues (L-368,935, L-740,093, YM022), pyrazolidimine analogues (LY 262,691) and glutamic acid analogues (CR2194). Many of these compounds have greater than 1000-fold selectivity for the CCKB over the CCKA receptor and some have greater than 10,000-fold selectivity. The pharmacology and effects of CCKB receptor antagonists on gastric acid secretion is briefly reviewed. Furthermore, the possible clinical usefulness of CCKB receptor antagonists in treating disorders of gastric acid secretion, in inhibiting the trophic effects of gastrin and in other clinical conditions is briefly discussed. RP Jensen, RT (reprint author), NIH,BLDG 10,ROOM 9C-103,10 CTR DR MSC 1804,BETHESDA,MD 20892, USA. NR 106 TC 12 Z9 12 U1 2 U2 2 PU YALE J BIOL MED INC PI NEW HAVEN PA 333 CEDAR ST, NEW HAVEN, CT 06510 SN 0044-0086 J9 YALE J BIOL MED JI Yale J. Biol. Med. PD MAY-JUN PY 1996 VL 69 IS 3 BP 245 EP 259 PG 15 WC Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; General & Internal Medicine; Research & Experimental Medicine GA XA295 UT WOS:A1996XA29500005 PM 9165693 ER PT J AU Petrakova, E Glaudemans, CPJ AF Petrakova, E Glaudemans, CPJ TI Synthesis of the methyl alpha-glycosides of some isomalto-oligosaccharides specifically deoxygenated at position C-3 SO CARBOHYDRATE RESEARCH LA English DT Article DE glycosides, methyl; glycosides, synthesis; oligosaccharides, alpha-isomalto-; sugars, deoxygenated ID STEREOSELECTIVE GLYCOSYLATION; SILVER PERCHLORATE; SUGARS; GLUCOSIDES; ALCOHOLS; DEOXY AB Methyl alpha-isomaltoside and methyl alpha-isomaltotrioside specifically deoxygenated at position C-3 of various glucopyranosyl units were synthesized by condensation of either 1,6-di-O-acetyl-2,4-di-O-benzyl-3-deoxy-alpha, beta-D-ribo-hexopyranose (7) or 1,6-di-O-acetyl-2,3,4-tri-O-benzyl-alpha,beta-D-glucopyranose [mediated by silver perchlorate and tin(IV) chloride] with suitably blocked derivatives of methyl alpha-D-glucopyranoside, its 3-deoxy analog (6), or methyl 3'-deoxy alpha-isomaltoside (10), respectively. (C) 1996 Published by Elsevier Science Ltd. C1 NIDDK,NATL INST HLTH,BETHESDA,MD 20892. NR 16 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD APR 30 PY 1996 VL 284 IS 2 BP 191 EP 205 DI 10.1016/0008-6215(96)00005-5 PG 15 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA UJ266 UT WOS:A1996UJ26600005 PM 8653719 ER PT J AU Zhang, SY Simonds, WF AF Zhang, SY Simonds, WF TI A carboxyl-terminal mutant of the G-protein beta subunit defective in phospholipase C-beta activation. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. NR 0 TC 5 Z9 5 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 6 EP 6 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100238 ER PT J AU Simeonova, PP Laster, MI AF Simeonova, PP Laster, MI TI Asbestos induction of interleukin-6 (IL-6) in lung epithelial cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS,ENVIRONM IMMUNOL SECT,RES TRIANGLE PK,NC 27709. NR 0 TC 1 Z9 1 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 34 EP 34 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100264 ER PT J AU Tsokos, M Vassilopoulos, D Szentendrei, T Quezado, M Karameris, A Tsokos, G AF Tsokos, M Vassilopoulos, D Szentendrei, T Quezado, M Karameris, A Tsokos, G TI Fas-mediated apoptosis in peripheral primitive neuroectodermal tumor (PNET) Ewing's sarcoma (ES). SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. WALTER REED ARMY MED CTR & INST RES,WASHINGTON,DC 20307. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 55 EP 55 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100285 ER PT J AU Li, Z Cheng, H Lederer, WJ Froehlich, J Lakatta, EG AF Li, Z Cheng, H Lederer, WJ Froehlich, J Lakatta, EG TI Enhanced proliferation and migration and altered cytoskeletal proteins in aortic early passage smooth muscle cells from old rats. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA,CARDIOVASC SCI LAB,NIH,BALTIMORE,MD 21224. UNIV MARYLAND,DEPT PHYSIOL,BALTIMORE,MD 21224. RI Lederer, William/B-1285-2010 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 96 EP 96 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100326 ER PT J AU Denkers, EY Yap, G Charest, H SchartonKersten, T Butcher, BA Sher, A AF Denkers, EY Yap, G Charest, H SchartonKersten, T Butcher, BA Sher, A TI Perforin knockout mice retain CD8+ T lymphocyte immunity to Toxoplasma gondii despite absence of parasite-specific CTL function SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. CORNELL UNIV,DEPT MICROBIOL & IMMUNOL,ITHACA,NY 14853. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 111 EP 111 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100340 ER PT J AU Doherty, TM Sher, A AF Doherty, TM Sher, A TI Altered course of Mycobacterium avium infection in mice with genetic defects in Th1 cytokine function. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID,PARASIT DIS LAB,IMMUNOBIOL SECT,NIH,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 121 EP 121 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100350 ER PT J AU Hartmann, K Mekori, YA Metcalfe, DD AF Hartmann, K Mekori, YA Metcalfe, DD TI Fas-/Apo-1-mediated apoptosis in murine mast cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NATL INST HLTH,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 134 EP 134 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100363 ER PT J AU Vliagoftis, H Metcalfe, DD AF Vliagoftis, H Metcalfe, DD TI Adhesion of human leukemic mast cells (HMC-1) to human laminin. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Vliagoftis, Harissios/C-6480-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 137 EP 137 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100369 ER PT J AU Lacana, E Vito, P DAdamio, L AF Lacana, E Vito, P DAdamio, L TI Functional cloning of ALG-4, a novel gene involved in programmed cell death SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID,T CELL MOLEC BIOL UNIT,MOL & CELLULAR BIOL LAB,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 164 EP 164 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100396 ER PT J AU Bethke, FR Short, J Riportella, J Shearer, GM AF Bethke, FR Short, J Riportella, J Shearer, GM TI PHA-stimulated cytokine profile can be predictive of proliferative response in human peripheral blood mononuclear cells (PBMCs). SO FASEB JOURNAL LA English DT Meeting Abstract C1 SAIC,FREDERICK,MD 21702. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. NCI,NIH,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 204 EP 204 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100436 ER PT J AU Zaitseva, M Mojcik, C Shevach, E Golding, H AF Zaitseva, M Mojcik, C Shevach, E Golding, H TI Protective role of the VLA4 integrin in dexamethasone-induced apoptosis in human thymocytes. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,BETHESDA,MD 20892. NIAID,NIH,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 260 EP 260 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100491 ER PT J AU Suzuki, H Shinkai, Y Love, PE Alt, FW Singer, A AF Suzuki, H Shinkai, Y Love, PE Alt, FW Singer, A TI Commitment of immature thymocytes to the CD4(+) T cell lineage independent of clonotypic TCR chains SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. CHILDRENS HOSP,DEPT GENET & PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NICHHD,LAB MAMMALIAN GENES & DEV,BETHESDA,MD 20892. RI Shinkai, Yoichi/N-3909-2014 OI Shinkai, Yoichi/0000-0002-6051-2484 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 262 EP 262 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100492 ER PT J AU Mojcik, CF Shevach, EM AF Mojcik, CF Shevach, EM TI Integrin usage by early thymocytes. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID,NIH,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 274 EP 274 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100504 ER PT J AU Weng, NP Levine, BL June, CH Hodes, RJ AF Weng, NP Levine, BL June, CH Hodes, RJ TI Regulated expression of telomerase activity in human T lymphocyte development and activation. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,NIH,EIB,BETHESDA,MD 20892. NIA,NIH,BETHESDA,MD 20892. USN,MED RES INST,ICBP,BETHESDA,MD 20889. RI Levine, Bruce/D-1688-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 278 EP 278 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100509 ER PT J AU Hathcock, KS Weng, NP Hodes, RJ AF Hathcock, KS Weng, NP Hodes, RJ TI Regulated expression of telomerase activity in normal murine lymphoid cell populations. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. NIA,NIH,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 279 EP 279 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100507 ER PT J AU DeRijk, R Michelson, D Gold, PW Sternberg, EM AF DeRijk, R Michelson, D Gold, PW Sternberg, EM TI Different sensitivity of IL-1 beta, IL-6 and TNF alpha to corticosteroids as measured ex vivo. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 312 EP 312 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100541 ER PT J AU Hama, N Paliogianni, F Kameda, H Mavrothalassitis, G Mimori, T Boumpas, DT AF Hama, N Paliogianni, F Kameda, H Mavrothalassitis, G Mimori, T Boumpas, DT TI Glucocorticoid modulation of cytokine gene transcription: Opposing effects on Th1 vs Th2 promoters. SO FASEB JOURNAL LA English DT Meeting Abstract C1 KEIO UNIV,SCH MED,TOKYO 152,JAPAN. NCI,FREDERICK,MD 21702. NIH,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 318 EP 318 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100547 ER PT J AU Chougnet, C Margolis, D Landay, AL Kessler, HA Shearer, GM AF Chougnet, C Margolis, D Landay, AL Kessler, HA Shearer, GM TI Contribution of prostaglandin (PG) E2 to the IL-12 defect in HIV-infected (HIV+) patients. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. UNIV MARYLAND,INST BIOTECHNOL,BALTIMORE,MD 21201. RUSH MED COLL,CHICAGO,IL 60612. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 328 EP 328 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100558 ER PT J AU Muller, S Nara, P Zhenshan, M Tovo, PA Goudsmit, J OToole, C AF Muller, S Nara, P Zhenshan, M Tovo, PA Goudsmit, J OToole, C TI Antibody avidity as marker for AIDS progression SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV KENTUCKY,LEXINGTON,KY 40536. NCI,FREDERICK,MD 21702. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 353 EP 353 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100582 ER PT J AU Pinto, LA Stake, J Landay, AL Berzofsky, JA Moss, RB Clerici, M Kessler, HA Shearer, GM AF Pinto, LA Stake, J Landay, AL Berzofsky, JA Moss, RB Clerici, M Kessler, HA Shearer, GM TI Cellular immunity to HIV antigens in HIV infected individuals and in seronegative, exposed health care workers SO FASEB JOURNAL LA English DT Meeting Abstract C1 RUSH MED COLL,CHICAGO,IL 60612. NCI,BETHESDA,MD 20892. IMMUNE RESPONSE CORP,CARLSBAD,CA 92008. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 355 EP 355 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100583 ER PT J AU Mahana, W Kindt, TJ AF Mahana, W Kindt, TJ TI HSP70 in HTLV-I infected cell lines and association with env protein gp46. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID,TWINBROOK FACIL 2,ROCKVILLE,MD 20852. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 358 EP 358 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100590 ER PT J AU Roberts, JL OShea, II Puck, JM Buckley, RH AF Roberts, JL OShea, II Puck, JM Buckley, RH TI Human autosomal recessive SCID due to Jak3 deficiency. SO FASEB JOURNAL LA English DT Meeting Abstract C1 DUKE UNIV,MED CTR,DURHAM,NC 27710. NIH,BETHESDA,MD 20814. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 370 EP 370 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100602 ER PT J AU Zhu, O Hollenbaugh, D Liu, T Wu, L Kanner, S Garrigues, J Blaese, RM Gown, A Aruffo, A Ochs, HD AF Zhu, O Hollenbaugh, D Liu, T Wu, L Kanner, S Garrigues, J Blaese, RM Gown, A Aruffo, A Ochs, HD TI The Wiskott-Aldrich syndrome protein. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV WASHINGTON,SEATTLE,WA 98195. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,SEATTLE,WA 98121. NIH,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 371 EP 371 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100600 ER PT J AU Rabin, RL Fuss, I Prussin, C McDyer, J Garraud, O Nutman, TB Fleisher, TA Seder, R Strober, W Holland, SM AF Rabin, RL Fuss, I Prussin, C McDyer, J Garraud, O Nutman, TB Fleisher, TA Seder, R Strober, W Holland, SM TI Characterization of an immunodeficiency manifest by severe viral skin infections, eczema, and asthma. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 372 EP 372 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100603 ER PT J AU Riva, A Krenacs, L Himmelmann, A Kehrl, JH AF Riva, A Krenacs, L Himmelmann, A Kehrl, JH TI The B cell transcription factor BSAP highly expressed in mantle zone B cells while is low in centroblasts. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID,LIR,BETHESDA,MD 20892. RI Krenacs, Laszlo/L-8063-2014 OI Krenacs, Laszlo/0000-0001-6541-3031 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 383 EP 383 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100615 ER PT J AU Allman, D Jain, A Staudt, LM AF Allman, D Jain, A Staudt, LM TI BCL-6 expression during B cell activation SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,METAB BRANCH,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 388 EP 388 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100617 ER PT J AU Chu, CC Paul, WE AF Chu, CC Paul, WE TI Fig1, an IL-4 induced gene expressed in mouse B and T cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 389 EP 389 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100620 ER PT J AU Yu, X Hodes, RJ AF Yu, X Hodes, RJ TI Stimulation of protein tyrosine phosphorylation by crosslinking B7-1 or B7-2 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NIA,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 394 EP 394 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100623 ER PT J AU Wu, ML Nakajima, H Takano, E Ebnet, K Zacharchuk, CM Henkart, PA AF Wu, ML Nakajima, H Takano, E Ebnet, K Zacharchuk, CM Henkart, PA TI The calcium-dependent cysteine protease calpain is required for TcR-induced FAS ligand upregulation. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,EXPTL IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NCI,LAB IMMUNE CELL BIOL,NIH,BETHESDA,MD 20892. KYOTO UNIV,LAB HUMAN TUMOR VIRUSES,SAKYO KU,KYOTO,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 400 EP 400 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100631 ER PT J AU Boirivant, M Pica, R DeMaria, R Testi, R Pal, F Pallone, F Strober, W AF Boirivant, M Pica, R DeMaria, R Testi, R Pal, F Pallone, F Strober, W TI Human lamina propria T cells (LPT) manifest enhanced Fas-mediated apoptosis SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV ROMA LA SAPIENZA,IST SUPER SANITA,I-00185 ROME,ITALY. UNIV ROMA TOR VERGATA,I-00173 ROME,ITALY. UNIV REGGIO CALABRIA,CATANZARO,ITALY. NIH,BETHESDA,MD 20892. RI BOIRIVANT, MONICA/B-9977-2016 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 403 EP 403 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100633 ER PT J AU Yang, XF Weber, GF Kozak, CA Cantor, H AF Yang, XF Weber, GF Kozak, CA Cantor, H TI Cloning of bcl-x gamma, a new bcl-x isoform that is preferentially expressed in CD4+ T cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV IMMUNOPATHOL,BOSTON,MA 02115. NIAID,NIH,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 412 EP 412 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100643 ER PT J AU Baskar, P Nagel, JE Adler, WH AF Baskar, P Nagel, JE Adler, WH TI Inhibition of IL-2 synthesis in Jurkat T-cells upon transfection with Bcl-2 gene. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,CLIN IMMUNOL SECT,NIH,BALTIMORE,MD 21224. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 413 EP 413 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100641 ER PT J AU Williams, MS Henkart, PA AF Williams, MS Henkart, PA TI Intracellular peroxide generation as an early event by some but not all apoptotic stimuli in T lymphocytes. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,EXPTL IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 415 EP 415 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100645 ER PT J AU Bruccoleri, A Harry, GJ AF Bruccoleri, A Harry, GJ TI Exposure to organotins upregulate IL-1a, TNFa, and IL-6 in mouse brain. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 435 EP 435 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100666 ER PT J AU Murakami, M Yoshimoto, T Paul, WE AF Murakami, M Yoshimoto, T Paul, WE TI Characterization of NK1.1+ T cells in gut and liver. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID,NIH,BETHESDA,MD 20892. HYOGO MED UNIV,NISHINOMIYA,HYOGO,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 452 EP 452 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100681 ER PT J AU Ludviksson, BR Gray, B Strober, W Ehrhardt, RO AF Ludviksson, BR Gray, B Strober, W Ehrhardt, RO TI Colitis-inducing thymocytes in the IL-2-/- mouse SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,NIH,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 459 EP 459 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100690 ER PT J AU Zimmermann, G Kazanietz, MG Blumberg, PM Taussig, R AF Zimmermann, G Kazanietz, MG Blumberg, PM Taussig, R TI Bold G protein alpha and beta gamma subunit regulation at mammalian adenylyl cyclases is modulated by protein kinase C SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV MICHIGAN,SCH MED,DEPT BIOL CHEM,ANN ARBOR,MI 48109. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 506 EP 506 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100736 ER PT J AU Hughes, FM Purdy, GD Cidlowski, JA AF Hughes, FM Purdy, GD Cidlowski, JA TI Intracellular potassium levels inhibit apoptotic DNA degradation SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS,LAB INTEGRAT BIOL,RES TRIANGLE PK,NC 27709. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 526 EP 526 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100757 ER PT J AU Huang, STJ Cidlowski, JA AF Huang, STJ Cidlowski, JA TI Fetal calf serum (FCS) depletion and dexamethasone (DEX) inhibit cell growth by a convergent pathway but induce apoptosis through parallel mechanisms SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV N CAROLINA,DEPT PHYSIOL,CHAPEL HILL,NC 27599. NIEHS,LAB INTEGRAT BIOL,RES TRIANGLE PK,NC 27709. RI Huang, Se-Te/F-6881-2013 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 528 EP 528 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100758 ER PT J AU Mitton, KP Tumminia, SJ Russell, P AF Mitton, KP Tumminia, SJ Russell, P TI Cleavage of MIP26 (aquaporin-0) accompanies cataractogenesis in transgenic mice expressing HIV-1 protease linked to the alpha A-crystallin promoter. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NEI,LAB MECHANISMS OCULAR DIS,NIH,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 529 EP 529 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100759 ER PT J AU Jayadev, S Preston, GA Barrett, JC Murphy, E AF Jayadev, S Preston, GA Barrett, JC Murphy, E TI Correlation between endoplasmic reticulum (ER) calcium stores and apoptosis. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 536 EP 536 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100768 ER PT J AU Combadiere, C Ahuja, SK Murphy, PM AF Combadiere, C Ahuja, SK Murphy, PM TI Cloning and functional expression of two human CC chemokine receptors. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID,LHD,NIH,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 545 EP 545 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100775 ER PT J AU Su, H Raymond, L Rockey, DD Fischer, E Hackstadt, T Caldwell, HD AF Su, H Raymond, L Rockey, DD Fischer, E Hackstadt, T Caldwell, HD TI A recombinant chlamydia trachomatis major outer membrane protein binds to heparan sulfate receptors on epithelial cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID,ROCKY MT LABS,HAMILTON,MT 59840. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 549 EP 549 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100780 ER PT J AU Kundu, GC Mukherjee, AB AF Kundu, GC Mukherjee, AB TI Invasion of the extracellular matrix by NIH 3T3 cells: Role of the high affinity phospholipase A2 receptor. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHHD,SECT DEV GENET,HDB,NIH,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 558 EP 558 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100788 ER PT J AU Berlett, BS Stadtman, ER AF Berlett, BS Stadtman, ER TI Carbon dioxide stimulates nitration of tyrosine residues and inhibits oxidation of methionine residues in Escherichia coli glutamine synthetase by peroxynitrite. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 585 EP 585 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100816 ER PT J AU Chao, CC Stadtman, ER AF Chao, CC Stadtman, ER TI Modification of protein hydrophobicity by oxidative systems. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 586 EP 586 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100814 ER PT J AU Netto, LES Stadtman, ER AF Netto, LES Stadtman, ER TI Iron-catalyzed oxidation of dithiols. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 587 EP 587 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100817 ER PT J AU Lubas, WA Hanover, J AF Lubas, WA Hanover, J TI Cloning and expression of an O-linked UDP-GlcNAc transferase from C-elegans. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK,NIH,CELL BIOL & BIOCHEM LAB,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 619 EP 619 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100849 ER PT J AU Bodenstein, Y Lim, D Duffy, L AF Bodenstein, Y Lim, D Duffy, L TI Improved isolation of a 62kD glycoprotein from stereocilia using Ponderosa pine pitch. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV ALASKA,DEPT BIOCHEM & CHEM,FAIRBANKS,AK 99775. NIDCD,CELL BIOL LAB,ROCKVILLE,MD 20850. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 625 EP 625 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100854 ER PT J AU McBride, AJ Kaslow, DC Ballou, WR Diggs, CL Lyon, J AF McBride, AJ Kaslow, DC Ballou, WR Diggs, CL Lyon, J TI Characterization of a recombinant Plasmodium falciparum MSP1 C-terminal fragment using conformation-specific monoclonal antibodies. SO FASEB JOURNAL LA English DT Meeting Abstract C1 WRAIR,WASHINGTON,DC 20307. UNIV EDINBURGH,EDINBURGH,MIDLOTHIAN,SCOTLAND. NIAID,NIH,BETHESDA,MD 20892. US AGCY INT DEV,WASHINGTON,DC 20523. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 683 EP 683 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100912 ER PT J AU Fisher, A Shi, Y Shah, MD Taniuchi, H Shiloach, Y AF Fisher, A Shi, Y Shah, MD Taniuchi, H Shiloach, Y TI A hypothetical network of residue-residue communications of cytochrome c to modulate function. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 686 EP 686 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100916 ER PT J AU Tucker, L Makhlouf, S Davis, L Krasnewich, D Anderson, B AF Tucker, L Makhlouf, S Davis, L Krasnewich, D Anderson, B TI Reactivity of a monoclonal antibody to transferrins from carbohydrate deficient glycoprotein syndromes. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NORTHWESTERN UNIV,SCH MED,CHICAGO,IL 60611. IMMTECH INT INC,EVANSTON,IL 60201. NIH,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 708 EP 708 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100939 ER PT J AU Wang, XW Jia, L Bennett, WP Elmore, LW Harris, CC AF Wang, XW Jia, L Bennett, WP Elmore, LW Harris, CC TI p53 tumor suppressor gene and molecular carcinogenesis. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,NIH,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 709 EP 709 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100937 ER PT J AU Zhang, Y McNeely, T Wahl, SM Wahl, LM AF Zhang, Y McNeely, T Wahl, SM Wahl, LM TI Secretory leukocyte protease inhibitor (SLPI) inhibits the production of matrix metalloproteinases (MMP) by monocytes. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDR,NIH,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 759 EP 759 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100991 ER EF