FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Srivastava, M Goping, G Caohuy, H McPhie, P Pollard, HB AF Srivastava, M Goping, G Caohuy, H McPhie, P Pollard, HB TI Detection and localization of synexin (Annexin VII) in Xenopus adult and embryonic tissues using an antibody to the Xenopus N-terminal PGQM repeat domain SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID CALCIUM-CHANNEL ACTIVITY; MEMBRANE-FUSION; PROTEIN; IDENTIFICATION; SEQUENCE; BILAYER; CELLS; GENE AB Synexin (Annexin VII) is a widely distributed member of the annexin gene family which forms calcium channels and drives calcium-dependent membrane fusion. In Xenopus laevis, different synexins contain two to six tandem repeats of the tetra amino acid sequence PGQM in the unique N-terminal, with a distribution specific to adult tissues and embryonic stages. Immunogold studies using the PGQM-specific polyclonal antibody showed that synexin is localized in adult muscle to myosin-rich A-bands, Z-bands, and T-tubules, and in other adult tissues to nuclei and mitochondria and other formed elements. In oocytes, synexin was also found associated with yolk granules. The PGQM: tandem repeats could represent interaction sites for other proteins, and we therefore synthesized a synthetic peptide containing the maximum six tandem repeats [NH2-(PGQM)(6)-Y-COOH] to test this hypothesis. We found that the peptide alone could specifically bind and crosslink to different proteins in a tissue-specific manner. In liver, it bound to a single 35-kDa protein. In muscle, it bound to four proteins (35, 45, 48, and 116 kDa). Therefore, we conclude that the PGQM domain is accessible to specific antibodies and that the PGQM repeat is sufficiently ordered to unambiguously identify specific binding proteins in different Xenopus tissues. (C) 1996 Academic Press, Inc. C1 NIDDKD,BIOCHEM PHARMACOL LAB,NIH,BETHESDA,MD 20892. RP Srivastava, M (reprint author), NIDDKD,CELL BIOL LAB,NIH,BETHESDA,MD 20892, USA. NR 25 TC 4 Z9 4 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 NOV 25 PY 1996 VL 229 IS 1 BP 14 EP 19 DI 10.1006/excr.1996.0338 PG 6 WC Oncology; Cell Biology SC Oncology; Cell Biology GA VV207 UT WOS:A1996VV20700003 PM 8940244 ER PT J AU Louie, AT Wahl, LM Hewlett, IK Epstein, JS Dhawan, S AF Louie, AT Wahl, LM Hewlett, IK Epstein, JS Dhawan, S TI Impaired antigen presentation to CD4+ T-cells by HIV-infected monocytes is related to down-modulation of CD4 expression on helper T-cells: Possible involvement of HIV-induced cellular factors SO FEBS LETTERS LA English DT Article DE HIV; AIDS; monocyte; T-cell; antigen presentation ID HUMAN-IMMUNODEFICIENCY-VIRUS; INVITRO; DYSFUNCTION; ACTIVATION; MEMBRANE; SYSTEM AB Defective antigen presentation by HIV-infected monocytes is related to severe immune dysfunction in patients with AIDS, although the mechanism by which this process occurs is not well defined, Here we report that reduced capacity by HIV-infected monocytes to stimulate or present antigen to CD4+ T-cells was mediated by cellular factors associated with the plasma membranes of HIV-infected monocytes, In contrast, soluble factors secreted by HIV-infected monocytes had little or no effect on T-cell stimulation, Reduced T-cell stimulation by HIV-infected monocytes was related to down-modulation of CD4 expression on helper T-cells and was not affected by the inclusion of anti-HIV-gp120 Ab, indicating the involvement of soluble or cell-associated viral envelope protein to be less likely, Exposure of CD4+ T-cells, that had been in co-culture with HIV-infected monocytes, to uninfected monocytes partially restored impaired T-cell stimulation, Thus, for the first time we report that altered capacity of HIV-infected monocytes to stimulate and present antigen to CD4+ T-cells is related to down-modulation of CD4 expression on T-cells, and appears to occur via membrane-associated cellular factors on HIV-infected monocytes. C1 DIV TRANSFUS TRANSMITTED DIS,IMMUNOCHEM LAB,ROCKVILLE,MD 20852. US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,MOL VIROL LAB,IMMUNOPATHOGENESIS SECT,BETHESDA,MD. NIDR,IMMUNOL LAB,BETHESDA,MD 20892. NR 24 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 25 PY 1996 VL 398 IS 1 BP 1 EP 6 DI 10.1016/S0014-5793(96)01164-7 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA VV878 UT WOS:A1996VV87800001 PM 8946943 ER PT J AU Schubert, U FerrerMontiel, AV OblattMontal, M Henklein, P Strebel, K Montal, M AF Schubert, U FerrerMontiel, AV OblattMontal, M Henklein, P Strebel, K Montal, M TI Identification of an ion channel activity of the Vpu transmembrane domain and its involvement in the regulation of virus release from HIV-1-infected cells SO FEBS LETTERS LA English DT Article DE channel protein; lipid bilayer; transmembrane helix; AIDS; reconstitution ID INTEGRAL MEMBRANE-PROTEIN; M2 PROTEIN; CYTOPLASMIC DOMAIN; XENOPUS OOCYTES; IMMUNODEFICIENCY; CD4; DEGRADATION; HIV-1; GENE; HEMAGGLUTININ AB HIV-1 Vpu catalyzes two independent functions, degradation of the virus receptor CD4 in the endoplasmic reticulum and enhancement of virus release from the cell surface, These activities are confined to distinct structural domains of Vpu, the cytoplasmic tail and the transmembrane (TM) anchor, respectively, It was recently reported that Vpu forms cation-selective ion channels in lipid bilayers, Here we report that this property of Vpu is a characteristic of its TM anchor. Expression of full-length Vpu in Xenopus oocytes increases membrane conductance. The Vpu-induced conductance is selective to monovalent cations over anions, does not discriminate Na+ over K+ and shows marginal permeability to divalent cations, Notably, introduction of the scrambled TM sequence into full-length Vpu abrogates its capacity to increase membrane conductance in oocytes and to promote virus release from infected cells, Reconstitution of synthetic Vpu fragments in lipid bilayers identified an ion channel activity for a sequence corresponding to the TM domain of Vpu. In contrast, a peptide with the same amino acid composition but with a scrambled sequence does not form ion channels, Our findings therefore suggest that the ability of Vpu to increase virus release from infected cells may be correlated with an ion channel activity of the TM domain, thereby providing a potential target for drug intervention based on the development of Vpu-specific channel blockers. C1 UNIV CALIF SAN DIEGO,DEPT BIOL,LA JOLLA,CA 92093. HUMBOLDT UNIV BERLIN,KLIN CHARITE,INST BIOCHEM,BERLIN,GERMANY. RP Schubert, U (reprint author), NIAID,MOL MICROBIOL LAB,NIH,BLDG 4,ROOM 312,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Ferrer-Montiel, Antonio/C-3072-2015 OI Ferrer-Montiel, Antonio/0000-0002-2973-6607 FU NIGMS NIH HHS [GM-49711] NR 37 TC 214 Z9 218 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 NOV 25 PY 1996 VL 398 IS 1 BP 12 EP 18 DI 10.1016/S0014-5793(96)01146-5 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA VV878 UT WOS:A1996VV87800003 PM 8946945 ER PT J AU Stefanacci, L Suzuki, WA Amaral, DG AF Stefanacci, L Suzuki, WA Amaral, DG TI Organization of connections between the amygdaloid complex and the perirhinal and parahippocampal cortices in macaque monkeys SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE amygdala; medial temporal lobe; memory; emotion; topography; cortical connections ID KLUVER-BUCY SYNDROME; RHESUS-MONKEY; HIPPOCAMPAL-FORMATION; RECIPROCAL CONNECTIONS; AFFERENT CONNECTIONS; MACACA-FASCICULARIS; ENTORHINAL CORTEX; MEMORY IMPAIRMENT; TEMPORAL CORTEX; PROJECTIONS AB Neuroanatomical studies in macaque monkeys have demonstrated that the perirhinal and parahippocampal (PRPH) cortices are strongly interconnected with the hippocampal formation. Recent behavioral evidence indicates that these cortical regions are importantly involved in normal recognition memory function. The PRPH cortices are also interconnected with the amygdaloid complex, although comparatively little is known about the precise topography of these connections. We investigated the topographic organization of reciprocal connections between the amygdala and the PRPH cortices by placing anterograde and retrograde tracers throughout these three regions. We found that there was an organized arrangement of connections between the amygdala and the PRPH cortices and that the deep (lateral, basal, and accessory basal) nuclei of the amygdaloid complex were the source of most connections between the amygdala and the PRPH cortices. The temporal polar regions of the perirhinal cortex had the strongest and most widespread interconnections with the amygdala. Connections from more caudal levels of the perirhinal cortex had a more discrete pattern of termination. Perirhinal inputs to the amygdala terminated primarily in the lateral nucleus, the magnocellular and parvicellular divisions of the basal nucleus, and the magnocellular division of the accessory basal nucleus. Return projections originated predominately in the lateral nucleus, the intermediate and parvicellular divisions of the basal nucleus, and the magnocellular division of the accessory basal nucleus. The interconnections between the amygdala and the parahippocampal cortex were substantially less robust than those with the perirhinal cortex and mainly involved the basal nucleus. Area TF was more strongly interconnected with the amygdala than was area TH. Input from the parahippocampal cortex terminated predominantly in the lateral half of the parvicellular division of the basal nucleus but also to a lesser extent in the magnocellular division of the basal nucleus and the lateral nucleus. Return projections originated predominantly in the magnocellular division of the basal nucleus and were directed almost exclusively to area TF. (C) 1996 Wiley-Liss, Inc. C1 UNIV CALIF DAVIS,CTR NEUROSCI,DAVIS,CA 95616. UNIV CALIF DAVIS,DEPT PSYCHIAT,DAVIS,CA 95616. UNIV CALIF SAN DIEGO,NEUROSCI GRP,LA JOLLA,CA 92037. NIMH,NEUROPSYCHOL LAB,NIH,BETHESDA,MD 20892. FU NCRR NIH HHS [RR 00169]; NIMH NIH HHS [R37 MH 41479]; NINDS NIH HHS [NS 16980] NR 61 TC 122 Z9 122 U1 1 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 NOV 25 PY 1996 VL 375 IS 4 BP 552 EP 582 PG 31 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA VQ833 UT WOS:A1996VQ83300002 PM 8930786 ER PT J AU Wang, H Moriwaki, A Wang, JB Uhl, GR Pickel, VM AF Wang, H Moriwaki, A Wang, JB Uhl, GR Pickel, VM TI Ultrastructural immunocytochemical localization of mu opioid receptors and Leu(5)-enkephalin in the patch compartment of the rat caudate-putamen nucleus SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE electron microscopy; endogenous opioid; extrasynaptic site; morphine; stereotyped behavior ID ELECTRON-MICROSCOPIC LOCALIZATION; IMMUNOGOLD-SILVER; OPIATE RECEPTOR; BINDING-SITES; MESSENGER-RNA; NEURONS; BRAIN; NEOSTRIATUM; EXPRESSION; LIGHT AB To delineate the cellular sites for the motor effects of opiates acting at the mu opioid receptor (MOR) in the rat caudate-putamen nucleus, we examined the ultrastructural immunogold and immunoperoxidase labeling of an antipeptide antiserum specific for the MOR. We also combined these labeling methods to examine the subcellular relationship between the MOR and the endogenous opioid peptide, Leu(5)-enkephalin (LE). By light microscopy, MOR-labeling was seen in a heterogeneous patchy distribution. Electron microscopic analysis of these patches showed that more than 80% of the total neuronal profiles (n = 1,586) containing MOR-like immunoreactivity (MOR-IR) were dendrites and dendritic spines. The remaining labeled profiles included a few perikarya and many axon terminals. MOR-IR was predominantly localized to extrasynaptic plasma membranes of dendrites, and to both synaptic vesicles and plasma membranes in terminals. Ten percent of the total MOR-labeled terminals (n = 272) formed asymmetric synapses with unlabeled or MOR-labeled dendritic spines. Terminals containing LE-IR formed synapses, in almost equal proportions, on MOR-labeled dendrites and dendritic spines, while over 80% of the unlabeled terminals formed synapses on MOR-labeled dendritic spines. Moreover, colocalization of MOR- and LE-IR was often seen in both dendrites and terminals. These results indicate that in patch compartments of the caudate-putamen nucleus, the MOR is mainly involved in extrasynaptic modulation of spiny neurons, including those that contain LE. In addition, the findings provide a cellular basis for presynaptic opioid modulation of neurotransmitter release through MOR located on axon terminals. (C) 1996 Wiley-Liss, Inc. C1 NIDA,INTRAMURAL RES PROGRAM,MOL NEUROBIOL BRANCH,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. RP Wang, H (reprint author), CORNELL UNIV MED COLL,DEPT NEUROL & NEUROSCI,DIV NEUROBIOL,411 E 69TH ST,NEW YORK,NY 10021, USA. FU NIDA NIH HHS [DA 04600]; NIMH NIH HHS [MH 00078] NR 61 TC 61 Z9 62 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD NOV 25 PY 1996 VL 375 IS 4 BP 659 EP 674 DI 10.1002/(SICI)1096-9861(19961125)375:4<659::AID-CNE7>3.0.CO;2-0 PG 16 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA VQ833 UT WOS:A1996VQ83300007 PM 8930791 ER PT J AU Dani, A Pietrini, P Furey, ML McIntosh, AR Grady, CL Horwitz, B Freo, U Alexander, GE Schapiro, MB AF Dani, A Pietrini, P Furey, ML McIntosh, AR Grady, CL Horwitz, B Freo, U Alexander, GE Schapiro, MB TI Brain cognition and metabolism in Down syndrome adults in association with development of dementia SO NEUROREPORT LA English DT Article DE brain; chromosome 21; dementia; Down syndrome; (18)FDG; PET ID CEREBRAL GLUCOSE-UTILIZATION; ALZHEIMERS-DISEASE; DOWNS-SYNDROME; PROTEIN; CT AB To identify changes in brain functions associated with the development of dementia, brain metabolism and cognition were assessed repeatedly in 12 adults with Down syndrome (DS) using positron emission tomography and neuropsychological tests. Ten subjects remained non-demented (ND) and showed no significant changes over time in cognitive measures or in cerebral metabolism. Two subjects developed dementia after 7 years. Brain functions were relatively stable prior to the onset of dementia; after the onset of dementia, both cognitive function and glucose metabolism in parietal and temporal brain regions known to be vulnerable to Alzheimer disease (AD) showed a rapid linear decline. These findings support the concept that brain functions are stable over time in ND individuals with DS and that decline of brain functions in DS subjects with dementia follows two distinct phases that correspond to the clinical progression of AD. This may have implications for timing of new therapeutic strategies. RP Dani, A (reprint author), NIA, NEUROSCI LAB,BRAIN AGING & DEMENTIA SECT,NIH, BLDG 10,ROOM 6C414, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. RI McIntosh, Anthony/G-4955-2011; Furey, Maura/H-5273-2013; OI McIntosh, Anthony/0000-0002-1784-5662 NR 17 TC 25 Z9 25 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD NOV 25 PY 1996 VL 7 IS 18 BP 2933 EP 2936 DI 10.1097/00001756-199611250-00026 PG 4 WC Neurosciences SC Neurosciences & Neurology GA WB359 UT WOS:A1996WB35900026 PM 9116213 ER PT J AU Levinson, DF Wildenauer, DB Schwab, SG Albus, M Hallmayer, J Lerer, B Maier, W Blackwood, D Muir, W StClair, D Morris, S Moises, HW Yang, L Kristbjarnarson, H Helgason, T Wiese, C Collier, DA Holmans, P Daniels, J Rees, M Asherson, P Roberts, Q Cardno, A Arranz, MJ Vallada, H McGuffin, D Owen, MJ Pulver, AE Antonarakis, SE Babb, R Blouin, JL DeMarchi, N Dombroski, B Housman, D Karayiorgou, M Ott, J Kasch, L Kazazian, H Lasseter, VK Loetscher, E Luebbert, H Nestadt, G Ton, C Wolyniec, PS Laurent, C deChaldee, M Thibaut, F Jay, M Samolyk, D Petit, M Campion, D Mallet, J Straub, RE MacLean, CJ Easter, SM ONeill, FA Walsh, D Kendler, KS Gejman, PV Cao, QH Gershon, E Badner, J Beshah, E Zhang, J Riley, BP Rajagopalan, S MogudiCarter, M Jenkins, T Williamson, R DeLisi, LE Garner, C Kelly, M LeDuc, C Cardon, L Lichter, J Harris, T Loftus, J Shields, G Comasi, M Vita, A Smith, A Dann, J Joslyn, G Gurling, H Kalsi, G Brynjolfsson, J Curtis, D Sigmundsson, T Butler, R Read, T Murphy, P Chen, ACH Petursson, H Byerley, B Hoff, M Holik, J Coon, H Nancarrow, DJ Crowe, RR Andreasen, N Silverman, JM Mohs, RC Siever, LJ Endicott, J Sharpe, L Walters, MK Lennon, DP Hayward, NK Sandkuijl, LA Mowry, BJ Aschauer, HN Meszaros, K Lenzinger, E Fuchs, K Heiden, AM Kruglyak, L Daly, MJ Matise, TC AF Levinson, DF Wildenauer, DB Schwab, SG Albus, M Hallmayer, J Lerer, B Maier, W Blackwood, D Muir, W StClair, D Morris, S Moises, HW Yang, L Kristbjarnarson, H Helgason, T Wiese, C Collier, DA Holmans, P Daniels, J Rees, M Asherson, P Roberts, Q Cardno, A Arranz, MJ Vallada, H McGuffin, D Owen, MJ Pulver, AE Antonarakis, SE Babb, R Blouin, JL DeMarchi, N Dombroski, B Housman, D Karayiorgou, M Ott, J Kasch, L Kazazian, H Lasseter, VK Loetscher, E Luebbert, H Nestadt, G Ton, C Wolyniec, PS Laurent, C deChaldee, M Thibaut, F Jay, M Samolyk, D Petit, M Campion, D Mallet, J Straub, RE MacLean, CJ Easter, SM ONeill, FA Walsh, D Kendler, KS Gejman, PV Cao, QH Gershon, E Badner, J Beshah, E Zhang, J Riley, BP Rajagopalan, S MogudiCarter, M Jenkins, T Williamson, R DeLisi, LE Garner, C Kelly, M LeDuc, C Cardon, L Lichter, J Harris, T Loftus, J Shields, G Comasi, M Vita, A Smith, A Dann, J Joslyn, G Gurling, H Kalsi, G Brynjolfsson, J Curtis, D Sigmundsson, T Butler, R Read, T Murphy, P Chen, ACH Petursson, H Byerley, B Hoff, M Holik, J Coon, H Nancarrow, DJ Crowe, RR Andreasen, N Silverman, JM Mohs, RC Siever, LJ Endicott, J Sharpe, L Walters, MK Lennon, DP Hayward, NK Sandkuijl, LA Mowry, BJ Aschauer, HN Meszaros, K Lenzinger, E Fuchs, K Heiden, AM Kruglyak, L Daly, MJ Matise, TC TI Additional support for schizophrenia linkage on chromosomes 6 and 8: A multicenter study SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE schizophrenia; genetic linkage; collaboration; polymorphism; genotype ID SIB-PAIR LINKAGE; GENOME-WIDE SEARCH; SUSCEPTIBILITY GENES; AFFECTIVE-DISORDERS; POTENTIAL LINKAGE; DNA MARKERS; HETEROGENEITY; RELATIVES; ILLNESS; LOCUS AB In response to reported schizophrenia linkage findings on chromosomes 3, 6 and 8, fourteen research groups genotyped 14 microsatellite markers in an unbiased, collaborative (New) sample of 403-567 informative pedigrees per marker, and in the Original sample which produced each finding (the Johns Hopkins University sample of 40-52 informative pedigrees for chromosomes 3 and 8, and the Medical College of Virginia sample of 156-191 informative pedigrees for chromosome 6). Primary planned analyses (New sample) were two-point heterogeneity lod score (lod2) tests (dominant and recessive affected-only models), and multipoint affected sibling pair (ASP) analysis, with a narrow diagnostic model schizophrenia and schizoaffective disorders), Regions with positive results were also analyzed in the Original and Combined samples. There was no evidence for linkage on chromosome 3. For chromosome 6, ASP maximum lod scores (MLS) were 2.19 (New sample, nominal p = .001) and. 2.68 (Combined sample, p = .0004). For chromosome 8, maximum lod2 scores (tests of linkage with heterogeneity) were 2.22 (New sample, p = .0014) and 3.06 (Combined sample, p = .00018). Results are interpreted as inconclusive hut suggestive of linkage in the latter two regions. We discuss possible reasons for failing to achieve a conclusive result in this large sample, Design issues and limitations of this type of collaborative study are discussed, and it is concluded that multicenter follow-up linkage studies of complex disorders can help to direct research efforts toward promising regions. C1 STATE MENTAL HOSP, HAAR, GERMANY. UNIV WESTERN AUSTRALIA, GRAYLANDS UWA CLIN RES UNIT, PERTH, WA 6009, AUSTRALIA. HEBREW UNIV JERUSALEM, HADASSAH MED CTR, DEPT PSYCHIAT, JERUSALEM, ISRAEL. UNIV EDINBURGH, ROYAL EDINBURGH HOSP, DEPT PSYCHIAT, EDINBURGH EH8 9YL, MIDLOTHIAN, SCOTLAND. WESTERN GEN HOSP, HUMAN GENET UNIT, MRC, EDINBURGH, MIDLOTHIAN, SCOTLAND. NATL UNIV HOSP, DEPT PSYCHIAT, REYKJAVIK, ICELAND. UNIV KIEL KLINIKUM, DEPT PSYCHIAT, KIEL, GERMANY. INST PSYCHIAT, DEPT PSYCHOL MED, MOL GENET SECT, LONDON SE5 8AF, ENGLAND. INST PSYCHIAT, DEPT NEUROPATHOL, MOL GENET SECT, LONDON SE5 8AF, ENGLAND. UNIV WALES COLL MED, DEPT PSYCHOL MED, CARDIFF CF4 4XN, S GLAM, WALES. UNIV WALES COLL MED, DEPT MED GENET, CARDIFF CF4 4XN, S GLAM, WALES. TEIKYO UNIV, SCH MED, DEPT PSYCHIAT, TOKYO 173, JAPAN. ST JAMES HOSP, TRINITY CTR HLTH SCI, DUBLIN 8, IRELAND. JOHNS HOPKINS UNIV, DEPT PEDIAT, BALTIMORE, MD 21218 USA. JOHNS HOPKINS UNIV, DEPT PSYCHIAT & BEHAV SCI, BALTIMORE, MD 21218 USA. UNIV GENEVA, DEPT GENET, SCH MED, CH-1211 GENEVA 4, SWITZERLAND. UNIV NAPLES 2, INST PSYCHIAT, NAPLES, ITALY. UNIV PENN, MED CTR, DEPT GENET, PHILADELPHIA, PA 19104 USA. MIT, CTR CANC RES, CAMBRIDGE, MA 02139 USA. ROCKEFELLER UNIV, HUMAN NEUROGENET LAB, NEW YORK, NY 10021 USA. ROCKEFELLER UNIV, LAB STAT GENET, NEW YORK, NY 10021 USA. SANDOZ PHARMA LTD, BASEL, SWITZERLAND. HOP LA PITIE SALPETRIERE, LAB GENET MOL NEUROTRANSMISS & PROC NEURODEGENER, CNRS, PARIS, FRANCE. CHS ST PAUL, ST PAUL, REUNION. CHS SOTTEVILLE, ROUEN, FRANCE. VIRGINIA COMMONWEALTH UNIV, MED COLL VIRGINIA, DEPT PSYCHIAT, RICHMOND, VA 23298 USA. VIRGINIA COMMONWEALTH UNIV, MED COLL VIRGINIA, DEPT HUMAN GENET, RICHMOND, VA 23298 USA. QUEENS UNIV BELFAST, DEPT PSYCHIAT, BELFAST, ANTRIM, NORTH IRELAND. HLTH RES BOARD, DUBLIN, IRELAND. NIMH, CLIN NEUROGENET BRANCH, BETHESDA, MD 20892 USA. ST MARYS HOSP, SCH MED, DEPT BIOCHEM & MOL GENET, LONDON W2 1PG, ENGLAND. BARAGWANATH HOSP, DEPT PSYCHIAT, SOWETO, SOUTH AFRICA. UNIV WITWATERSRAND, DEPT HUMAN GENET, SCH PATHOL, S AFRICAN INST MED RES, JOHANNESBURG, SOUTH AFRICA. SEQUANA THERAPEUT INC, SAN DIEGO, CA USA. SUNY STONY BROOK, DEPT PSYCHIAT, STONY BROOK, NY 11794 USA. WARNEFORD HOSP, DEPT PSYCHIAT, OXFORD OX3 7JX, ENGLAND. UNIV MILAN, I-20122 MILAN, ITALY. UCL, SCH MED, MOL PSYCHIAT LAB, DEPT PSYCHIAT, LONDON W1N 8AA, ENGLAND. UNIV ICELAND, DEPT PSYCHIAT, BORGARSPITINN, IS-101 REYKJAVIK, ICELAND. LONDON HOSP, COLL MED, DEPT PSYCHOL MED, LONDON, ENGLAND. UNIV UTAH, MED CTR, DEPT PSYCHIAT, SALT LAKE CITY, UT USA. ALLEGHENY UNIV HLTH SCI, DEPT PSYCHIAT, PHILADELPHIA, PA 19102 USA. UNIV QUEENSLAND, DEPT PSYCHIAT, WOLSTON PK HOSP, BRISBANE, QLD, AUSTRALIA. QUEENSLAND INST MED RES, BRISBANE, QLD 4006, AUSTRALIA. UNIV IOWA, COLL MED, DEPT PSYCHIAT, IOWA CITY, IA 52242 USA. UNIV IOWA, COLL MED, MENTAL HLTH CLIN RES CTR, IOWA CITY, IA 52242 USA. MT SINAI SCH MED, DEPT PSYCHIAT, NEW YORK, NY USA. COLUMBIA UNIV, NEW YORK STATE PSYCHIAT INST, NEW YORK, NY USA. ERASMUS UNIV, DEPT CLIN GENET, NL-3000 DR ROTTERDAM, NETHERLANDS. LEIDEN UNIV, DEPT GENET, NL-2300 RA LEIDEN, NETHERLANDS. UNIV GRONINGEN, DEPT MED GENET, NL-9700 AB GRONINGEN, NETHERLANDS. UNIV VIENNA, HOSP PSYCHIAT, DEPT GEN PSYCHIAT, VIENNA, AUSTRIA. COLUMBIA UNIV COLL PHYS & SURG, DEPT PSYCHIAT, NEW YORK, NY 10032 USA. WHITEHEAD INST BIOMED RES, CAMBRIDGE, MA USA. RP Levinson, DF (reprint author), UNIV BONN, DEPT PSYCHIAT, D-5300 BONN, GERMANY. RI turton, miranda/F-4682-2011; Gurling, Hugh/A-5029-2010; Rees, Mark/J-3129-2012; Antonarakis, Stylianos/N-8866-2014; hayward, nicholas/C-1367-2015; Holmans, Peter/F-4518-2015; Vallada, Homero/D-1333-2014; OI Antonarakis, Stylianos/0000-0001-8907-5823; hayward, nicholas/0000-0003-4760-1033; Holmans, Peter/0000-0003-0870-9412; Vallada, Homero/0000-0001-5123-8295; Moises, Hans/0000-0003-1522-3226 NR 55 TC 142 Z9 144 U1 4 U2 12 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 22 PY 1996 VL 67 IS 6 BP 580 EP 594 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA VV138 UT WOS:A1996VV13800011 ER PT J AU Beebe, LE Roberts, ES Fornwald, LW Hollenberg, PF Alworth, WL AF Beebe, LE Roberts, ES Fornwald, LW Hollenberg, PF Alworth, WL TI Mechanism-based inhibition of mouse P4502b-10 by selected arylalkynes SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE cytochrome P450; suicide inhibition; arylalkynes; mouse; liver; lung ID P450 ISOZYMES; IDENTIFICATION; RAT; 1,4-BIS<2-(3,5-DICHLOROPYRIDYLOXY)>BENZENE; CYTOCHROME-P450; TUMORS; LUNG; 2B1 AB Suicide inhibitors of cytochrome P450 families are excellent tools to predict which isoforms mediate the metabolism/activation of a variety of chemical agents. We compared the inhibitory effects of several arylalkynes on mouse cytochromes P450 with published data for the rat model. The inhibition of P4502b specific dealkylation of benzyloxyresorufin by 2-ethynylnaphthalene (2-EN), 5-phenyl-1-pentyne (PPY), 4-phenyl-1-butyne (PBY), and 9-ethynylphenanthrene (9-EPh) was measured in hepatic microsomes from male mice treated with 1,4-bis[2-(3,5-dichloropyridyloxy)]-benzene (TCPOBOP) to induce cytochrome P4502b. Pulmonary microsomes were prepared from untreated mice. 9-EPh, 2-EN, and PPY caused a time-, concentration-, and NADPH-dependent loss in P4502b activity in both tissues. PBY, however, demonstrated this type of inhibition only in liver microsomes. The IC50 was calculated for both liver and lung microsomes and compared with published K-i (concentration required for half-maximal inhibition) or K-I (concentration required for half-maximal inactivation) values for the rat. PPY, PBY, and 9-EPh were equally effective inhibitors of mouse P4502b and rat P4502B1. 2-EN was a 5- to 10-fold less potent inhibitor of mouse P4502b, as compared with the rat, even though it was shown to bind to the active site of the mouse isoform as demonstrated by its metabolism to 2-naphthylacetic acid. These data suggest that the active site of the mouse P4502b enzyme is functionally similar to the rat P4502B isoform, with the exception of the disparity in its susceptibility to inactivation by 2-EN as measured by the K-i values. Copyright (C) 1996 Elsevier Science Inc. C1 UNIV MICHIGAN,DEPT PHARMACOL,ANN ARBOR,MI 48109. NCI,FREDERICK CANC RES & DEV CTR,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD 21702. TULANE UNIV,DEPT CHEM,NEW ORLEANS,LA 70118. RP Beebe, LE (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. RI Hollenberg, Paul/A-7538-2009 NR 16 TC 14 Z9 14 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD NOV 22 PY 1996 VL 52 IS 10 BP 1507 EP 1513 DI 10.1016/S0006-2952(96)00525-4 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VQ073 UT WOS:A1996VQ07300004 PM 8937464 ER PT J AU Duncan, KLK Duncan, MD ALley, MC Sausville, EA AF Duncan, KLK Duncan, MD ALley, MC Sausville, EA TI Cucurbitacin E-induced disruption of the actin and vimentin cytoskeleton in prostate carcinoma cells SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE actin; cytoskeleton; steroid; prostate neoplasm drug treatment; vimentin ID CYTOCHALASIN-B; F-ACTIN; CYTOKINESIS; BINDING; POLYMERIZATION; TRITERPENES; PHALLOIDIN; PROTEIN AB Cucurbitacin E has been identified by an empiric screening strategy as a sterol with potent growth inhibitory activity in vitro directed against. prostate carcinoma explants (IC50 of 7-50 nM in 2- to 6-day exposures). The mechanism of cucurbitacin cytoxicity has not been elucidated previously. In the present study, we observed that cucurbitacin E caused marked disruption of the actin cytoskeleton, and in a series of cucurbitacin analogues, anti-proliferative activity correlated directly with the disruption of the F-actin cytoskeleton. The distribution of vimentin was also altered in cells exposed to cucurbitacin E, as vimentin associated with drug-induced membrane blebs. The appearance of microtubules was unaffected. Western blot analysis of intracellular actin in cells exposed to cucurbitacins and quantitation of rhodamine phalloidin binding support the hypothesis that cucurbitacin treatment leads to an inappropriate increase in the filamentous or polymerized actin fraction in prostate carcinoma cells. We conclude that cucurbitacins are potent disrupters of cytoskeletal integrity. Prostate carcinoma cells appear notably sensitive to growth inhibition by cucurbitacin E. Copyright (C) 1996 Elsevier Science Inc. C1 NCI,BIOL CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NCI,BIOL TESTING BRANCH,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT DIAG & CTR,NIH,BETHESDA,MD 20892. VET ADM MED CTR,SURG SERV,WASHINGTON,DC 20422. RI Duncan, Kimberly /C-3655-2013 NR 38 TC 88 Z9 97 U1 0 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD NOV 22 PY 1996 VL 52 IS 10 BP 1553 EP 1560 DI 10.1016/S0006-2952(96)00557-6 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VQ073 UT WOS:A1996VQ07300010 PM 8937470 ER PT J AU Hellriegel, ET Matwyshyn, GA Fei, PW Dragnev, KH Nims, RW Lubet, RA Kong, ANT AF Hellriegel, ET Matwyshyn, GA Fei, PW Dragnev, KH Nims, RW Lubet, RA Kong, ANT TI Regulation of gene expression of various phase I and phase II drug-metabolizing enzymes by tamoxifen in rat liver SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE tamoxifen, chemoprevention; UDP-glucuronosyltransferase; sulfotransferase; glutathione S-transferase; epoxide hydrolase; cytochrome P450; rat liver; mRNA/gene regulation ID GLUTATHIONE-S-TRANSFERASE; AMINO-ACID-SEQUENCE; BREAST-CANCER; MOLECULAR-CLONING; MESSENGER-RNA; UDP GLUCURONOSYLTRANSFERASE; ESTROGEN SULFOTRANSFERASE; MONOOXYGENASE ACTIVITIES; CHEMOPREVENTIVE AGENTS; PHENOLIC ANTIOXIDANTS AB The objective of the present investigation was to evaluate the effect of tamoxifen (TAM) on the gene expression of different phase I and phase II drug-metabolizing enzymes. Groups of male and female F344/NCr rats were administered either corn oil or TAM (2.8 to 45 mg/kg body wt x 14 days) dissolved in corn oil by gavage. An additional group of rats received a diet supplemented with phenobarbital (PB, 500 ppm). Northern blot analyses of total liver RNA were conducted using [P-32]-labeled cDNA or oligonucleotide probes coding for different sulfotransferase (ST), UDP-glucuronosyltransferase (UGT), glutathione S-transferase (GST), epoxide hydrolase (EPH) or cytochrome P450 (CYP) mRNA transcripts. In male rats, TAM increased the levels of STel, STa and STpl mRNAs, whereas PB increased only the STel mRNA. In female rats, there was no expression of STel and STHA mRNA in either control or TAM-treated animals. TAM and PB increased UGT(Br/p) mRNAs in all rats, whereas UGT(ml) mRNA was elevated only in PB-treated animals. EPH mRNA was UGT elevated markedly in all rats treated with TAM and PB, whereas GST(ya/yc) mRNA was highly increased by PB, but only marginally increased by TAM. Finally, TAM increased CYP3A1 mRNA, and slightly increased CYP2B1 mRNA, whereas PB highly elevated mRNAs for both of these CYP genes. In conclusion, treatments of rats with TAM increased the mRNA levels of many phase I and phase II drug-metabolizing enzymes, and this pleiotypic response to TAM seems to be different from other prototype inducers such as PB or dioxin (TCDD). Copyright (C) 1996 Elsevier Science Inc. C1 UNIV ILLINOIS,COLL PHARM,DEPT PHARMACEUT & PHAMACODYNAM,CTR PHARMACEUT BIOTECHNOL,CHICAGO,IL 60607. THOMAS JEFFERSON UNIV,DEPT MED,DIV CLIN PHARMACOL,PHILADELPHIA,PA 19107. NCI,COMPARAT CARCINOGENESIS LAB,CHEM SECT,FREDERICK CANC RES & DEV CTR,FREDERICK,MD. FU NIEHS NIH HHS [ES 06887]; NIGMS NIH HHS [GM 49172] NR 53 TC 25 Z9 25 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD NOV 22 PY 1996 VL 52 IS 10 BP 1561 EP 1568 DI 10.1016/S0006-2952(96)00560-6 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VQ073 UT WOS:A1996VQ07300011 PM 8937471 ER PT J AU Liu, J Barry, CE Besra, GS Nikaido, H AF Liu, J Barry, CE Besra, GS Nikaido, H TI Mycolic acid structure determines the fluidity of the mycobacterial cell wall SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUBERCULOSIS; IDENTIFICATION; PERMEABILITY; BIOSYNTHESIS; RESISTANT; SMEGMATIS; CHELONAE AB The low permeability of the mycobacterial cell wall is thought to contribute to the well known resistance of mycobacteria to antibiotics and chemotherapeutic agents, We have used differential scanning calorimetry to demonstrate that the high temperature phase transition observed in purified cell walls, usually in the 60-70 degrees C range, suggestive of a lipid environment of extremely low fluidity, can also be observed in whole organisms and in cell walls from which much of the free lipids was removed by extraction with Triton X-114, A survey of seven mycobacterial species demonstrated that this high temperature transition was a general property of these organisms, Cell walls isolated from two Corynebacterium species, which contain much shorter corynemycolic acids, displayed a much lower temperature transition, suggesting that the transition temperature was directly correlated to the length of mycolic acid. Methyl esters of mycolic acids were found to have a phase transition temperature that was linearly related to the amount of fl ans-mycolate. Both Mycobacterium avium and M. smegmatis responded to increasing growth temperature by increasing the proportion of trans-mycolate and displaying a correspondingly higher melting temperature, Whole cells of M. smegmatis grown at higher temperature allowed a less rapid influx of two lipophilic agents, norfloxacin and chenodeoxycholate. These results provide strong evidence that the nature of mycolic acid plays a crucial role in determining the fluidity and permeability of mycobacterial cell wall. C1 UNIV CALIF BERKELEY,DEPT MOL & CELL BIOL,BERKELEY,CA 94720. NIAID,ROCKY MT LABS,TB RES UNIT,HAMILTON,MT 59840. COLORADO STATE UNIV,DEPT MICROBIOL,FT COLLINS,CO 80523. RI Barry, III, Clifton/H-3839-2012; OI Besra, Gurdyal/0000-0002-5605-0395; Liu, Jun/0000-0002-0522-6733 FU Intramural NIH HHS [Z01 AI000783-11]; NIAID NIH HHS [AI-09644, AI-18357, AI-33702] NR 30 TC 173 Z9 182 U1 1 U2 17 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 NOV 22 PY 1996 VL 271 IS 47 BP 29545 EP 29551 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VU525 UT WOS:A1996VU52500009 PM 8939881 ER PT J AU Dong, G Schulick, AH DeYoung, MB Dichek, DA AF Dong, G Schulick, AH DeYoung, MB Dichek, DA TI Identification of a cis-acting sequence in the human plasminogen activator inhibitor type-1 gene that mediates transforming growth factor-beta 1 responsiveness in endothelium in vivo SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-ADHESION MOLECULE-1; NECROSIS-FACTOR-ALPHA; MESSENGER-RNA LEVELS; HEP G2 CELLS; FACTOR-BETA; EXPRESSION; TISSUE; INDUCTION; PAI-1; LIPOPOLYSACCHARIDE AB The mechanism of regulation of the plasminogen activator inhibitor type-1 (PAI-1) gene by transforming growth factor-beta 1 (TGF-beta 1) was studied in vitro and in vivo in endothelial cells. We constructed adenovirus vectors containing PAI-1 5'-flanking sequences driving expression of a beta p-galactosidase (beta-gal) reporter gene, Cultured bovine endothelial cells were transduced with the vectors and treated with TGF-beta 1. beta-Gal expression was up-regulated 10-20-fold by TGF-beta 1 when vectors contained 799-base pair (bp) of 5'-flanking sequence, but only minimally (2-3 fold) from a vector containing only 82-bp of 5' PAI-1 flanking sequence. TGF-beta 1 up-regulated p-gal expression at the mRNA level, congruently with TGF-beta P1 up-regulation of expression of the endogenous PAI-1 gene. The constructs were transduced into intact rat carotid endothelium, and TGF-P1 was injected systemically. In vivo, TGF-beta 1 up-regulated endothelium-specific expression of beta-gal 3-fold (p < 0.03) from a vector containing the 799-bp sequence, but did not alter expression from a vector containing the 82-bp sequence. The sequence between -799 and -82 mediates up-regulation of reporter gene expression by TGF-beta 1 in endothelial cells in vitro and in vivo. This general method permits the elucidation of mechanisms of gene regulation by physiologic stimuli delivered to the endothelium of intact animals. C1 UNIV CALIF SAN FRANCISCO,GLADSTONE INST CARDIOVASC DIS,SAN FRANCISCO,CA 94141. NHLBI,MOL HEMATOL BRANCH,NIH,BETHESDA,MD 20892. NR 50 TC 39 Z9 41 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 22 PY 1996 VL 271 IS 47 BP 29969 EP 29977 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VU525 UT WOS:A1996VU52500070 PM 8939942 ER PT J AU Powers, C Krutzsch, H Gardner, K AF Powers, C Krutzsch, H Gardner, K TI Modulation of JunD center dot AP-1 DNA binding activity by AP-1-associated factor 1 (AF-1) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VIRUS TRANSACTIVATOR TAX; TRANSCRIPTION FACTORS; SIGNALING PATHWAY; GENE FAMILY; FOS GENE; T-CELLS; JUN; AP-1; PROTEIN; PHOSPHORYLATION AB AP-1-associated factor 1 (AF-1), is a novel protein complex that dramatically enhances the assembly of JunD-containing dimers onto AP-1 consensus sites. We describe the partial purification of AF-1 from nuclear extracts of the T-cell line MLA 144 by ionic, hydrophobic and gel filtration chromatography. AF-1 is a DNA-binding protein composed of low molecular mass polypeptides of 7-17 kDa that exists in solution as a 34-kDa complex. JunD interactions with DNA are accelerated in the presence of AF-1 through the formation of a true tri-molecular complex with JunD dimers and DNA that assembles much more rapidly on DNA than JunD alone. DNA binding analysis of AF-1 interaction with JunD . AP-1 and DNA shows that AF-1 increases the DNA binding affinity of JunD for AP-1 sites over 100-fold. DNA cleavage footprint analysis of isolated AF-1 . JunD DNA complexes shows that the ternary complex makes nearly twice as many contacts with DNA than JunD dimers alone. AF-1 interacts readily, but differentially with Jun homodimers and Jun . Fos heterodimers. These findings distinguish AF-1 as a significant protein-specific modulator of AP-1 . JunD in T-cells. C1 NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. RI Powers, Ciaran/E-3890-2011 NR 34 TC 22 Z9 22 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 NOV 22 PY 1996 VL 271 IS 47 BP 30089 EP 30095 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VU525 UT WOS:A1996VU52500085 PM 8939957 ER PT J AU Glowa, JR Fantegrossi, WE Lewis, DB Matecka, D Rice, KC Rothman, RB AF Glowa, JR Fantegrossi, WE Lewis, DB Matecka, D Rice, KC Rothman, RB TI Sustained decrease in cocaine-maintained responding in rhesus monkeys with 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]4-(3-hydroxy-3-phenylpropyl)piper azinyl decanoate, a long-acting ester derivative of GBR 12909 SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID RAT C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PSYCHIAT,BETHESDA,MD 20814. NIDDK,MED CHEM LAB,NIH,BETHESDA,MD 20892. NIDA,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD. FU NIDA NIH HHS [DA 09820]; ONDIEH CDC HHS [RA-ND-94-24] NR 15 TC 74 Z9 75 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 22 PY 1996 VL 39 IS 24 BP 4689 EP 4691 DI 10.1021/jm960551t PG 3 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA VU595 UT WOS:A1996VU59500001 PM 8941381 ER PT J AU Matecka, D Rothman, RB Radesca, L deCosta, BR Dersch, CM Partilla, JS Pert, A Glowa, JR Wojnicki, FHE Rice, KC AF Matecka, D Rothman, RB Radesca, L deCosta, BR Dersch, CM Partilla, JS Pert, A Glowa, JR Wojnicki, FHE Rice, KC TI Development of novel, potent, and selective dopamine reuptake inhibitors through alteration of the piperazine ring of 1-[2-(diphenylmethoxy)ethyl]- and 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazines (GBR 12935 and GBR 12909) SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID BIOGENIC-AMINE TRANSPORTERS; RAT CAUDATE MEMBRANES; BINDING-SITES; COCAINE ANTAGONISTS; SIGMA-RECEPTORS; RHESUS-MONKEYS; GBR-12909; ANALOGS; PHARMACOLOGY; AFFINITY AB The design, synthesis, and biological evaluation of compounds related to the dopamine (DA) uptake inhibitors: 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine (1) and 1-[2-[bis-(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl) piperazine (2) (GBR 12395 and GBR 12909, respectively), directed toward the development and identification of new ligands interacting with high potency and selectivity at the dopamine transporter (DAT) is reported. The substitution of the piperazine ring in the GBR structure with other diamine moieties resulted in the retention of the high affinity of new ligands for the DAT. Some of the modified GBR analogs (e.g. 8, 10, (-)-49, or (-)-50) displayed substantially higher selectivity (4736- to 693-fold) for the dopamine (DA) versus the serotonin (5HT) reuptake site than the parent compounds. The bis(p-fluoro) substitution in the (diphenylmethoxy)ethyl fragment slightly increased the affinity of the ligands at the DA reuptake site but reduced their selectivity at this site (e.g. 9 and 8, 11 and 10, or 17 and 16, respectively). Congeners, such as the series of monosubstituted and symmetrically disubstituted piperazines and trans-2,5-dimethylpiperazines, which lack the (diphenylmethoxy)ethyl substituent lost the affinity for the DAT yet exhibited very high potency for binding to the a receptors (e.g. 28). The chiral pyrrolidine derivatives of 1, (-)-49, and (+)-49, exhibited an enantioselectivity ratio of 181 and 146 for the inhibition of DA reuptake and binding to the DAT, respectively. C1 NIDDKD,MED CHEM LAB,NIH,BETHESDA,MD 20892. NIMH,BIOL PSYCHIAT BRANCH,NIH,BETHESDA,MD 20892. NIDA,CLIN PSYCHOPHARMACOL SECT,IRP,NIH,BALTIMORE,MD 21224. NR 65 TC 64 Z9 66 U1 2 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 22 PY 1996 VL 39 IS 24 BP 4704 EP 4716 DI 10.1021/jm960305h PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA VU595 UT WOS:A1996VU59500003 PM 8941383 ER PT J AU Chen, ZM Izenwasser, S Katz, JL Zhu, NJ Klein, CL Trudell, ML AF Chen, ZM Izenwasser, S Katz, JL Zhu, NJ Klein, CL Trudell, ML TI Synthesis and dopamine transporter affinity of 2-(methoxycarbonyl)-9-methyl-3-phenyl-9-azabicyclo[3.3.1]nonane derivatives SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; POSITRON EMISSION TOMOGRAPHY; COCAINE RECOGNITION SITES; H-3 COCAINE; UPTAKE INHIBITORS; RAT STRIATUM; BINDING; ANALOGS; RECEPTOR; DISCOVERY AB A series of 9-methyl-3 beta-phenyl-2-substituted-9-azabicyclo[3.3.1]nonane derivatives were synthesized and evaluated as cocaine-binding site ligands at the dopamine transporter (DAT). The conformation of the bicyclic structures and the stereochemistry of the substituents were determined by NMR and X-ray crystallography. The in vitro binding affinity (K-i) of the 9-azabicyclo[3.3.1]nonane derivatives was measured in rat caudate-putamen tissue, and they were found to be 100-fold (K-i = 2-14 mu M) less potent than cocaine and other tropane analogs. From these results it is evident that the cocaine-binding site at the DAT is very sensitive to structural modifications of the unsubstituted methylene bridge [C(6)-C(7)] of cocaine and cocaine-like compounds. C1 UNIV NEW ORLEANS,DEPT CHEM,NEW ORLEANS,LA 70148. NIDA,INTRAMURAL RES PROGRAM,BALTIMORE,MD 21224. XAVIER UNIV,DEPT CHEM,NEW ORLEANS,LA 70125. RI Izenwasser, Sari/G-9193-2012; OI Katz, Jonathan/0000-0002-1068-1159 FU NIDA NIH HHS [R29 DA08055] NR 37 TC 24 Z9 24 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 22 PY 1996 VL 39 IS 24 BP 4744 EP 4749 DI 10.1021/jm960507d PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA VU595 UT WOS:A1996VU59500007 PM 8941387 ER PT J AU Smith, JR Freije, D Carpten, JD Gronberg, H Xu, JF Isaacs, SD Brownstein, MJ Bova, GS Guo, H Bujnovszky, P Nusskern, DR Damber, JE Bergh, A Emanuelsson, M Kallioniemi, OP WalkerDaniels, J BaileyWilson, JE Beaty, TH Meyers, DA Walsh, PC Collins, FS Trent, JM Isaacs, WB AF Smith, JR Freije, D Carpten, JD Gronberg, H Xu, JF Isaacs, SD Brownstein, MJ Bova, GS Guo, H Bujnovszky, P Nusskern, DR Damber, JE Bergh, A Emanuelsson, M Kallioniemi, OP WalkerDaniels, J BaileyWilson, JE Beaty, TH Meyers, DA Walsh, PC Collins, FS Trent, JM Isaacs, WB TI Major susceptibility locus for prostate cancer on chromosome 1 suggested by a genome-wide search SO SCIENCE LA English DT Article ID INHERITANCE AB Despite its high prevalence, very little is known regarding genetic predisposition to prostate cancer. A genome-wide scan performed in 66 high-risk prostate cancer families has provided evidence of linkage to the long arm of chromosome 1 (1q24-25). Analysis of an additional set of 25 North American and Swedish families with markers in this region resulted in significant evidence of linkage in the combined set of 91 families. The data provide strong evidence of a major prostate cancer susceptibility locus on chromosome 1. C1 NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,JAMES BUCHANAN BRADY UROL INST,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. NIMH,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD. UNIV MICHIGAN,DEPT INTERNAL MED,ANN ARBOR,MI 48109. UMEA UNIV,DEPT PATHOL,S-90187 UMEA,SWEDEN. UMEA UNIV,DEPT UROL,UMEA,SWEDEN. RI Brownstein, Michael/B-8609-2009; Kallioniemi, Olli/H-5111-2011; Smith, Jeff/C-3484-2012; Kallioniemi, Olli/H-4738-2012; OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332; Bailey-Wilson, Joan/0000-0002-9153-2920 FU NCI NIH HHS [CA58236] NR 19 TC 561 Z9 570 U1 2 U2 11 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 22 PY 1996 VL 274 IS 5291 BP 1371 EP 1374 DI 10.1126/science.274.5291.1371 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VU954 UT WOS:A1996VU95400052 PM 8910276 ER PT J AU Gallai, M Sebestyen, A Nagy, P Kovalszky, N Onody, T Thorgeirsson, SS AF Gallai, M Sebestyen, A Nagy, P Kovalszky, N Onody, T Thorgeirsson, SS TI Proteoglycan gene expression in rat liver after partial hepatectomy SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HEPARAN-SULFATE PROTEOGLYCAN; GROWTH-FACTOR-BETA; EXTRACELLULAR-MATRIX; MOLECULAR MECHANISMS; HEPATIC REGENERATION; MESSENGER-RNA; HUMAN COLON; PERLECAN; DECORIN; ORGANOGENESIS AB Liver regeneration is regulated by several factors. Among these extracellular matrix plays a crucial role in the restoration of normal structure. Proteoglycans are major component of extracellular matrix and they are able to bind growth factors implicated in liver growth. Wa studied syndecan, perlecan, fibroglycan, and decorin expression after partial hepatectomy In rats by Northern blot analysis. A strong early upregulation was observed at 30 min in decorin expression which was followed by the first syndecan and perlecan peaks at 2 and 4 hours after hepatectomy. Ar 2 ? hours, which is the peak oi. hepatocyte DNA synthesis, all these three proteoglycans had elevated steady state transcript level. Fibroglycan message decreased after partial hepatectomy anti remained low during the experimental period. The different expression pattern of the proteoglycans suggests that these extracellular matrix components may selectively influence the regeneration process. (C) 1996 Academic Press, Inc. C1 NCI,EXPT CARCINOGENESIS LAB,BETHESDA,MD 20892. RP Gallai, M (reprint author), SEMMELWEIS UNIV MED,INST PATHOL & EXPT CANC RES 1,ULLOI UT 26,H-1085 BUDAPEST,HUNGARY. NR 40 TC 14 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 21 PY 1996 VL 228 IS 3 BP 690 EP 694 DI 10.1006/bbrc.1996.1718 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VV002 UT WOS:A1996VV00200006 PM 8941340 ER PT J AU Luo, C Copeland, NG Jenkins, NA Edelhoff, S Disteche, C Hogan, PG Rao, A AF Luo, C Copeland, NG Jenkins, NA Edelhoff, S Disteche, C Hogan, PG Rao, A TI Normal function of the transcription factor NFAT1 in wasted mice. Chromosome localization of NFAT1 gene SO GENE LA English DT Article DE DNA-binding protein; genetic diseases; RNA splicing; cytokine gene expression; T cell activation; transcription regulation ID IMMUNOSUPPRESSIVE DRUGS; ATAXIA-TELANGIECTASIA; NUCLEAR FACTOR; NF-ATP; FAMILY; MOUSE; CELLS; PROTEINS; BINDING; DEPHOSPHORYLATION AB NFAT1 (NFATp), a cytosolic component of the nuclear factor of activated T cells (NFAT), is encoded by a single gene which was mapped to mouse chromosome 2 in the vicinity of the wasted (wst) locus. Although wasted mice display a severe immune disorder, they express normal levels of NFAT1 protein. The NFAT1 protein in wasted mice is properly regulated and possesses comparable DNA binding activity as that in their littermate controls. Therefore, the wasted phenotype is not due to a defect in the expression or early regulation of the NFAT1 protein. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL & MOL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21701. UNIV WASHINGTON,SCH MED,DEPT PATHOL,SEATTLE,WA 98195. FU NCI NIH HHS [CA 42471]; NIGMS NIH HHS [GM 46227, GM 46883] NR 31 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD NOV 21 PY 1996 VL 180 IS 1-2 BP 29 EP 36 DI 10.1016/S0378-1119(96)00396-4 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA VY054 UT WOS:A1996VY05400005 PM 8973343 ER PT J AU Kwon, TK Nagel, JE Buchholz, MA Nordin, AA AF Kwon, TK Nagel, JE Buchholz, MA Nordin, AA TI Characterization of the murine cyclin-dependent kinase inhibitor gene p27(Kip1) SO GENE LA English DT Article DE cell cycle; T-cell; cdk inhibitor; promoter; cyclin; transcription factors ID PROMOTER; EXPRESSION; PROTEIN; E2F; TRANSCRIPTION; LYMPHOCYTES; ACTIVATION; SITES AB The cyclin-dependent kinase inhibitor p27(Kip1) plays an important role in regulating cell-cycle progression. p27(Kip1) directly inhibits the catalytic activity of cyclin/cdks (cyclin-dependent kinase) complexes and/or interferes physically with cyclin/cdks activation by CAK. Interestingly, the expression level of p27(Kip1) mRNA was maximal in resting G(0) T-cells and rapidly declined following anti-CD3 activation. We report here the cloning of p27(Kip1) gene from murine genomic DNA and the functional analysis of the promoter of the p27(Kip1) gene. The gene consists of at least three exons and spans more than 5.6 kb of DNA. Primer extension and nuclease S1 protection analysis revealed two major transcription initiation sites. The promoter region lacked a TATA box but contained potential binding sites for the transcriptional factors including two Spl, CRE, Myb and NFkB located at positions -153, -178, -286, -875, and -1011, respectively. To analyze the regulatory mechanisms controlling p27(Kip1) gene expression, we characterized the 5'-flanking region from nt -1609 to +178. The -326 to -615 region contained positive regulatory elements. C1 NIA,CLIN IMMUNOL SECT,GERONTOL RES CTR,NATL INST HLTH,BALTIMORE,MD 21224. NR 28 TC 61 Z9 62 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD NOV 21 PY 1996 VL 180 IS 1-2 BP 113 EP 120 DI 10.1016/S0378-1119(96)00416-7 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA VY054 UT WOS:A1996VY05400016 PM 8973354 ER PT J AU Yang, YS Lijam, N Sussman, DJ Tsang, M AF Yang, YS Lijam, N Sussman, DJ Tsang, M TI Genomic organization of mouse dishevelled genes SO GENE LA English DT Article DE what signal transduction; exon/intron comparison; development ID INT-1 PROTOONCOGENE; DROSOPHILA; POLARITY; HOMOLOG AB We report the isolation and characterization of two new genomic loci corresponding to the mouse Dishevelled (Dvl) genes Dvl2 and Dvl3. The Dvl genes are homologs of the Drosophila dsh segment polarity gene, and are involved in the Wnt/wingless signal transduction pathway. Dvl2 and Dvl3 genomic clones were isolated from a mouse 129 strain lambda FIXII genomic library and have identical exon/intron organization to Dvl1. All three Dishevelled genes span 15 exons and 14 introns and have a number of conserved splice junction sites. C1 UNIV MARYLAND,DIV HUMAN GENET,DEPT OBSTET & GYNECOL,BALTIMORE,MD 21201. NIH,LGDR,NCHGR,BETHESDA,MD 20892. RI TSANG, Michael/E-2758-2013; Tsang, Michael/I-9305-2014 OI TSANG, Michael/0000-0001-6384-2422; Tsang, Michael/0000-0001-7123-0063 FU NCI NIH HHS [R55 CA63929] NR 18 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD NOV 21 PY 1996 VL 180 IS 1-2 BP 121 EP 123 DI 10.1016/S0378-1119(96)00430-1 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA VY054 UT WOS:A1996VY05400017 PM 8973355 ER PT J AU Nestel, FP Colwill, K Harper, S Pawson, T Anderson, SK AF Nestel, FP Colwill, K Harper, S Pawson, T Anderson, SK TI RS cyclophilins: Identification of an NK-TR(1)-related cyclophilin SO GENE LA English DT Article DE cDNA; Clk; nuclear kinase; pre-mRNA splicing; two-hybrid screen ID NATURAL-KILLER-CELLS; HOMOLOGOUS DOMAIN; SR PROTEINS; RECOGNITION; TUMOR AB We report the isolation of a large cyclophilin protein containing RS (arginine-serine) repeats from a yeast two-hybrid screen using Clk (CDC28/cdc2-liLe kinase) as a probe. This Clk associating RS-cyclophilin (CARS-Cyp) possesses 39% homology to the NK-TR, (natural killer tumor recognition protein-1) we have previously characterized (Anderson et al. (1993) Proc. Natl. Acad. Sci. USA 90 (1993) 542-546). CARS-Cyp is expressed in a variety of tissues and cell types, and codes for a protein with a predicted mass of 89 kDa containing a cyclophilin-related domain, two Nopp140 (nucleolar phosphoprotein of 140 kDa)-related domains, and a large RS domain. The RS-cyclophilins, a novel class of proteins, may play an important role in the regulation of pre-mRNA splicing. C1 NCI,EXPT IMMUNOL LAB,DBS,FCRDC,FREDERICK,MD 21702. MT SINAI HOSP,SAMUEL LUNENFELD RES INST,PROGRAMME MOL BIOL & CANC,TORONTO,ON M5G 1X5,CANADA. UNIV TORONTO,DEPT MOL & MED GENET,TORONTO,ON,CANADA. SAIC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. RI Anderson, Stephen/B-1727-2012; Colwill, Karen/K-5101-2012; Pawson, Tony/E-4578-2013 OI Anderson, Stephen/0000-0002-7856-4266; Colwill, Karen/0000-0002-8979-1659; NR 14 TC 40 Z9 41 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD NOV 21 PY 1996 VL 180 IS 1-2 BP 151 EP 155 DI 10.1016/S0378-1119(96)00436-2 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA VY054 UT WOS:A1996VY05400022 PM 8973360 ER PT J AU Agulnick, AD Taira, M Breen, JJ Tanaka, T Dawid, IB Westphal, H AF Agulnick, AD Taira, M Breen, JJ Tanaka, T Dawid, IB Westphal, H TI Interactions of the LIM-domain-binding factor Ldb1 with LIM homeodomain proteins SO NATURE LA English DT Article ID GENE; ORGANIZER; MUSCLE; XENOPUS; XLIM-1; ZYXIN AB THE LIM homeodomain (LIM-HD) proteins, which contain two tandem LIM domains followed by a homeodomain, are critical transcriptional regulators of embryonic development(1-5). The LIM domain is a conserved cysteine-rich zinc-binding motif found in LIM-HD and LMO (rhombotin or Ttg) proteins, cytoskeletal components, LIM kinases and other proteins(1). LIM domains are protein-protein interaction motifs(1), can binding of LIM-HD proteins to DNA(6,7) and can negatively regulate LIM-HD protein function(8). How LIM domains exert these regulatory effects is not known. We have now isolated a new LIM-domain-binding factor, LdB1, on the basis of tis ability to interact with the LIM-HD protein Lhx1 (Lim1)(9). High-affinity binding by Ldb1 requires paired LIM domains and is restricted to the related subgroup of LIM domains found in LIM-HD and LMO proteins. The highly conserved Xenopus Lbd protein XLbd1, interacts with Xlim-1, the Xenopus orthologue of Lhx1. When injected into Xenopus embryos, XLbd1 (or Lbd1) can synergize with Xlim-1 in the formation of partial secondary axes and in activation of the genes encoding goosecoid (gsc), chordin, NCAM and XCG7, demonstrating a functional as well as a physical interaction between the two proteins. C1 NICHHD,GENET MOL LAB,NIH,BETHESDA,MD 20892. RP Agulnick, AD (reprint author), NICHHD,LAB MAMMALIAN GENES & DEV,NIH,BETHESDA,MD 20892, USA. NR 23 TC 249 Z9 258 U1 0 U2 5 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD NOV 21 PY 1996 VL 384 IS 6606 BP 270 EP 272 DI 10.1038/384270a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VU381 UT WOS:A1996VU38100053 PM 8918878 ER PT J AU Wang, MH MonteroJulian, FA Dauny, I Leonard, EJ AF Wang, MH MonteroJulian, FA Dauny, I Leonard, EJ TI Requirement of phosphatidylinositol-3 kinase for epithelial cell migration activated by human macrophage stimulating protein SO ONCOGENE LA English DT Article DE MSP; RON; PI-3 kinase; migration ID HEPATOCYTE GROWTH-FACTOR; FACTOR SCATTER FACTOR; MET PROTOONCOGENE PRODUCT; HA-RAS MUTATION; TYROSINE KINASE; FACTOR-RECEPTOR; SIGNAL TRANSDUCTION; MOLECULAR-CLONING; 3-KINASE; FAMILY AB Macrophage stimulating protein (MSP) is a ligand for the RON receptor protein tyrosine kinase. Activation of RON in murine resident macrophages results in cell shape change and migration. We studied cell movement induced by MSP in different types of human epithelial cells and the possible role of phosphatidylinositol-3 (PI-3) kinase in RON-mediated signal transduction. We observed specific and saturable binding of I-125-MSP to RON on several epithelial cell lines. In addition to activation and phosphorylation of RON, MSP also induced tyrosine phosphorylation of the PI-3 kinase p85 subunit in a time-dependent manner, with a peak at 15 min. Moreover, phosphorylated RON formed complex with PI-3 kinase in both HK-NOC keratinocyte and RON cDNA-transfected MDCK cells. An in vitro protein interaction assay confirmed that PI-3 kinase from a lysate of MSP-activated cells bound to pure RON protein. MSP, at a concentration range of 1 to 5 nM, induced migration of three epithelial cell lines. This effect was inhibited by wortmannin, a specific inhibitor for PI-3 kinase, with an IC50 of 10 nM. MSP-induced shape change in murine resident peritoneal macrophages was also abolished by wortmannin. These data suggest that activation of PI-3 kinase is required for MSP-induced epithelial cell migration. The stimulation by MSP of epithelial cell movement may have implications for tissue repair, wound healing, and tumor metastasis. C1 NCI,IMMUNOBIOL LAB,IMMUNOPATHOL SECT,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,NIH,FREDERICK,MD 21702. IMMUNOTECH SA,ANTIBODY DEPT,MARSEILLE 9,FRANCE. NR 50 TC 75 Z9 75 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 21 PY 1996 VL 13 IS 10 BP 2167 EP 2175 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VV145 UT WOS:A1996VV14500014 PM 8950984 ER PT J AU Leonardsen, L DeClue, JE Lybaek, H Lowy, DR Willumsen, BM AF Leonardsen, L DeClue, JE Lybaek, H Lowy, DR Willumsen, BM TI Rasp21 sequences opposite the nucleotide binding pocket are required for GRF-mediated nucleotide release SO ONCOGENE LA English DT Article DE Rasp21-mutants; GRF; GNEF; Ras-loop 7; nucleotide-exchange ID MURINE SARCOMA-VIRUS; GTPASE-ACTIVATING PROTEIN; SWITCH-II REGION; GUANINE-NUCLEOTIDE; SACCHAROMYCES-CEREVISIAE; EXCHANGE FACTOR; CATALYTIC DOMAIN; SIGNAL TRANSDUCTION; TERMINAL DOMAIN; TYROSINE KINASE AB The substrate requirements for the catalytic activity of the mouse Cdc25 homolog Guanine nucleotide Release Factor, GRF, were determined using the catalytic domain of GRF expressed in insect cells and E. coli expressed H-Ras mutants. We found a requirement for the loop 7 residues in Ras (amino acids 102 to 105) for stimulation of guanine nucleotide release. The dependence on the switch I and II regions of Rasp21 (encompassing the residues that shift position in the GTP- versus GDP-bound protein), which had been seen with Sdc25-mediated exchange, was also found for GRF. In addition, the sensitivity of H-Ras to GRF was abolished when residues 130-139 were replaced by proline-aspartic acid-glutamine, whereas substitution of the entire loop 8 (residues 123-130 replaced by leucine-isoleucine-arginine) had no effect on the stimulation of guanine nucleotide release by GRF. Substrate activity of Ras proteins were independent of their post-translational processing, GDP release was stimulated threefold more effectively by GRF than was GTP release, and no major differences were found between the mammalian N-, H- and K-Ras proteins. Examining the responsiveness of the Ras protein from S. pombe and the human Ras like proteins RhoA, Rap1A, Rad and G25K revealed a strict Ras specificity; of these only S. pombe Ras was GRF sensitive. C1 UNIV COPENHAGEN, DEPT MOL CELL BIOL, DK-1353 COPENHAGEN, DENMARK. NCI, CELLULAR ONCOL LAB, BETHESDA, MD 20892 USA. RI Willumsen, Berthe/H-1903-2012 OI Willumsen, Berthe/0000-0002-2277-6999 NR 54 TC 15 Z9 15 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 21 PY 1996 VL 13 IS 10 BP 2177 EP 2187 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VV145 UT WOS:A1996VV14500015 PM 8950985 ER PT J AU Nakamura, T Jenkins, NA Copeland, NG AF Nakamura, T Jenkins, NA Copeland, NG TI Identification of a new family of Pbx-related homeobox genes SO ONCOGENE LA English DT Article DE Meis; Pbx; Hox; homeobox; transcription ID HUMAN PROTOONCOGENE PBX1; DNA-BINDING SPECIFICITY; TRANSLOCATION PROTEIN; MYELOID-LEUKEMIA; LINKAGE MAP; PRE-B; EXTRADENTICLE; MOUSE; MICE; ARABIDOPSIS AB The expression of Meis1 (a novel Pbx-related homeobox gene) and either Hoxa7 or Hoxa9 are coactivated by retroviral integration in BXH2 murine myeloid leukemias (T Nakamura, DA Largaespada, JD Shaughnessy Jr, NA Jenkins and NG Copeland (1996) Nature Genet. 12: 149-153). As Pbx proteins are Hox cofactors, which cooperatively bind DNA with Hox proteins to modulate the otherwise similar DNA bind specificities of Hox proteins, these results suggested that Meis1 may function as a cofactor for Hoxa7 and Hoxa9 in the induction of murine myeloid leukemias. By DNA cross-hybridization we have identified two Meis1-related genes, Meis2 and Meis3. Sequence analysis revealed extensive amino acid similarity among the three Meis proteins both within and outside of the homeodomain. Phylogenetic analysis showed that the Meis genes belong to a distinct family of Pbx-related genes. Chromosome mapping studies indicated that Meis2 and Meis3 are unlinked to Meis1 and map to mouse chromosome 2 and 7, respectively. The Meis genes displayed distinct but overlapping patterns of expression in normal tissues and were expressed in some cases of murine myeloid leukemia. The identification of two additional Meis genes identifies a new family of potential Hox cofactors as well as two new potential disease genes. C1 NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 52 TC 86 Z9 88 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 21 PY 1996 VL 13 IS 10 BP 2235 EP 2242 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VV145 UT WOS:A1996VV14500021 PM 8950991 ER PT J AU Smith, ML Kontny, HU Zhan, QM Sreenath, A OConnor, PM Fornace, AJ AF Smith, ML Kontny, HU Zhan, QM Sreenath, A OConnor, PM Fornace, AJ TI Antisense GADD45 expression results in decreased DNA repair and sensitizes cells to uv-irradiation or cisplatin SO ONCOGENE LA English DT Article DE p53; GADD45; repair ID NUCLEOTIDE EXCISION-REPAIR; C-TERMINAL DOMAIN; NUCLEAR ANTIGEN; GROWTH ARREST; G1 CHECKPOINT; P53; DAMAGE; PROTEIN; INHIBITION; REPLICATION AB Loss of p53 function in cancer cells commonly results in a condition of genomic instability. This is believed to emanate from a loss of the G(1) checkpoint response to DNA damage. While the role of p53 in the induction of a G(1) arrest is well-accepted, additional p53 functions are being discovered. Cell cycle checkpoints presumably function to allow additional time for DNA repair after damage is incurred, however, genetic studies in yeast suggest that components of the checkpoint pathway may also be involved in DNA lesion processing (Lydall and Weinert, 1995). Recent evidence suggests that this may also be the case for p53, as suggested by numerous reports linking p53 function to DNA repair. Thus, loss of p53 function might contribute to genomic instability independent of G(1)-arrest. In the present study, we explored the effect of p53 disruption and consequences of antisense GADD45 expression on the DNA repair capacity of human colon carcinoma RKO cells. DNA repair was assayed using host-cell reactivation of u.v.-damaged reporter plasmids and unscheduled DNA synthesis experiments in transiently-transfected cells. We show that a number of transfected genes that suppress p53 function reduce the ability of cells to repair u.v.-induced DNA damage. Moreover, cells in which expression of the p53-regulated gene GADD45 was blocked by antisense vectors, also showed altered levels of DNA repair. Blocking Gadd45 expression by constitutive antisense expression sensitized cells to killing by u.v.-radiation or by cis-platinum (II) diamine-dichloride (CDDP, or cisplatin), a cancer chemotherapy drug which produces DNA cross-links. These findings suggest the involvement of downstream effecters of the p53 pathway in the coordination of cell cycle arrest and DNA repair. RP Smith, ML (reprint author), NCI,DIV CANC TREATMENT,MOL PHARMACOL LAB,DEV THERAPEUT PROGRAM,NIH,BLDG 37,ROOM 5C09,BETHESDA,MD 20892, USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 44 TC 138 Z9 145 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 21 PY 1996 VL 13 IS 10 BP 2255 EP 2263 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VV145 UT WOS:A1996VV14500023 PM 8950993 ER PT J AU Zhan, QM Alamo, I Yu, K Boise, LH Cherney, B Tosato, G OConnor, PM Fornace, AJ AF Zhan, QM Alamo, I Yu, K Boise, LH Cherney, B Tosato, G OConnor, PM Fornace, AJ TI The apoptosis-associated gamma-ray response of BCL-X(L) depends on normal p53 function SO ONCOGENE LA English DT Article DE BCL-X(L); p53; apoptosis; ionizing radiation ID TUMOR-SUPPRESSOR P53; CELL-CYCLE; BCL-X; ATAXIA-TELANGIECTASIA; CANCER-CELLS; DNA-DAMAGE; BAX GENE; IN-VIVO; C-MYC; EXPRESSION AB We have investigated the effect of DNA damage on the expression of BCL-X, a member of the BCL-2 family. BCL-X mRNA levels were found to increase upon exposure human cells to ionizing radiation (IR). The Bcl-X(L) protein, but not Bcl-X(S), was identified to be induced by IR. Like BAX, another member of the BCL-2 family and a p53-regulated gene, the induction of BCL-X(L) was dependent on normal p53 function and required that cells have an apoptosis-susceptible phenotype. The induction of BCL-X(L) was rapid, transient and dose-dependent. The mRNA level peaked at 4 h and returned to baseline by 24 h post-irradiation. In agreement with the increased transcript level, Bcl-X(L) protein level was also observed to increase in cells with wild-type p53 where IR triggered apoptosis. In addition, a survey of the BCL-X(L) mRNA basal levels in human cells with known apoptotic responses showed that low basal levels of BCL-X(L) mRNA in cells were highly correlated with a strong ability of cells to undergo IR-induced apoptosis. On the other hand, high levels of basal BCL-X(L) were correlated,vith the resistance of cells to IR-induced apoptosis regardless of p53 status. These results indicate that BCL-2 and BCL-X(L) behave differently in response to DNA damage treatment even though they both are able to protect cells from p53-mediated apoptosis; along with down-regulation of BCL-2, BCL-X(L) was up-regulated by IR in human cells with wild-type p53 and susceptibility to IR-induced apoptosis. We speculate that the physiological function of increased BCL-X(L) protein would be expected to probably limit the severity and length of BAX effect in order to maintain a proper threshold for apoptosis and to complete cell cycle arrest activated by p53. C1 UNIV CHICAGO,GWEN KNAPP CTR LUPUS & IMMUNOL,CHICAGO,IL 60637. US FDA,CTR BIOL,BETHESDA,MD 20892. RP Zhan, QM (reprint author), NCI,MOL PHARMACOL LAB,DIV BASIC SCI,ROOM 5C09,BLDG 37,BETHESDA,MD 20892, USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 35 TC 68 Z9 74 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 21 PY 1996 VL 13 IS 10 BP 2287 EP 2293 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VV145 UT WOS:A1996VV14500027 PM 8950997 ER PT J AU Black, FL Biggar, RJ Lal, RB Gabbai, AA Vieira, JPB AF Black, FL Biggar, RJ Lal, RB Gabbai, AA Vieira, JPB TI Twenty-five years of HTLV type II follow-up with a possible case of tropical spastic paraparesis in the Kayapo, a Brazilian Indian tribe SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID LYMPHOTROPIC VIRUS TYPE-1; INFECTION; RETROVIRUSES; TRANSMISSION; POPULATIONS AB A longitudinal study, spanning 25 years and great demographic and cultural change, found a persistently high prevalence of human T-lymphotropic virus type II (HTLV-II) in the Xikrin Kayapo Indians of Brazil, More than 10% of the children continue to develop immune reactions to the virus in infancy, a sharp increase in seroprevalence occurs between ages 15 and 30 years, and prevalence in older women still approaches 100%, This suggests that the major modes of transmission (breast milk and sexual activity) have not changed, The demonstration of stable maintenance of HTLV-II in one ethnic group makes migration theories of its dispersal more plausible, However, the infection may not be a negligible burden on population survival: at least 1 of 62 persons followed until age 40 years died of possible tropical spastic paraparesis (TSP). C1 YALE UNIV, SCH MED, DEPT PUBL HLTH, NEW HAVEN, CT 06520 USA. NCI, VIRAL EPIDEMIOL BRANCH, ROCKVILLE, MD 20850 USA. CTR DIS CONTROL, RETROVIRUS DIS BRANCH, ATLANTA, GA 30333 USA. DEPT NEUROL, BR-04023900 SAO PAULO, BRAZIL. ESCOLA PAULISTA MED, BR-04023900 SAO PAULO, BRAZIL. NR 23 TC 16 Z9 20 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV 20 PY 1996 VL 12 IS 17 BP 1623 EP 1627 DI 10.1089/aid.1996.12.1623 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA VV292 UT WOS:A1996VV29200007 PM 8947297 ER PT J AU Peters, R Sikorski, R AF Peters, R Sikorski, R TI The Web, unplugged - Hardware, software, and connections SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID INTERNET C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. NATL CANC INST,BETHESDA,MD. RP Peters, R (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,WANG BLDG,ACC-1,FRUIT ST,BOSTON,MA 02114, USA. NR 11 TC 7 Z9 7 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 NOV 20 PY 1996 VL 276 IS 19 BP 1607 EP 1608 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA VT025 UT WOS:A1996VT02500036 ER PT J AU Merrill, R AF Merrill, R TI Stat bite - Trends in prostate cancer incidence SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT News Item RP Merrill, R (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 20 PY 1996 VL 88 IS 22 BP 1617 EP 1617 DI 10.1093/jnci/88.22.1617 PG 1 WC Oncology SC Oncology GA VU793 UT WOS:A1996VU79300008 ER PT J AU Rosenberg, SA AF Rosenberg, SA TI Development of cancer immunotherapies based on identification of the genes encoding cancer regression antigens SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID TUMOR-INFILTRATING LYMPHOCYTES; CYTOLYTIC T-LYMPHOCYTES; HUMAN BREAST-CANCER; HUMAN-MELANOMA; AUTOLOGOUS TUMOR; CELL RECEPTOR; METASTATIC MELANOMA; IN-VITRO; CYTOKINE SECRETION; MULTIPLE EPITOPES AB Tumor-infiltrating lymphocytes (TILs) have been grown from patients with metastatic melanoma and administered to the autologous patients to identify those TIL populations capable of mediating tumor regression. These TILs have been used to clone the genes that encode melanoma antigens. With the use of this strategy, we have identified six different genes encoding antigens restricted by multiple HLA alleles that appear to be related to tumor regression in patients. These antigens are now being used to develop immunization approaches for the treatment of patients with metastatic melanoma. The availability of genes encoding unique cancer antigens is opening new possibilities for the development of immunotherapies for the treatment of patients with cancer. RP Rosenberg, SA (reprint author), NCI,SURG BRANCH,DIV CLIN SCI,NIH,BLDG 10,RM 2B42,BETHESDA,MD 20892, USA. NR 63 TC 111 Z9 114 U1 0 U2 2 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 NOV 20 PY 1996 VL 88 IS 22 BP 1635 EP 1644 DI 10.1093/jnci/88.22.1635 PG 10 WC Oncology SC Oncology GA VU793 UT WOS:A1996VU79300012 PM 8931607 ER PT J AU Parmar, MKB Ungerleider, RS Simon, R AF Parmar, MKB Ungerleider, RS Simon, R TI Assessing whether to perform a confirmatory randomized clinical trial SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CELL LUNG-CANCER; ADJUVANT THERAPY; COLON-CARCINOMA; FLUOROURACIL; LEVAMISOLE; RADIATION AB Background: A confirmatory randomized clinical trial is a trial that is aimed at assessing whether a treatment effect observed in a previous randomized trial (or trials) is real and important. There is often considerable disagreement about the need for such confirmatory trials. Purpose: Our aim is to provide a general statistical framework for evaluating whether a confirmatory trial is warranted in a particular situation. Methods and Results: The results of two clinical trials are considered: 1) a Cancer and Leukemia Group B trial comparing induction chemotherapy plus radiotherapy with radiotherapy alone in the treatment of patients with locally advanced non-small-cell lung cancer and 2) a North Central Cancer Treatment Group trial comparing surgery plus adjuvant chemotherapy with surgery alone in the treatment of patients with advanced colon cancer. In our analysis, we argue that differences in the interpretation of results from a randomized trial are based on differences in prior beliefs about the efficacy of the treatment(s) under study. We believe that a major factor in the decision to perform a confirmatory trial is prior skepticism about the clinical worth of the treatment in question. Both the level of prior skepticism and the minimum treatment effect deemed clinically worthwhile require subjective judgment. We develop a Bayesian framework to allow differences in interpretation to be examined systematically and the need for a confirmatory trial to be assessed. Our model allows the addition of prior belief (specified in the form of a prior distribution of treatment effect) to the results of a trial to yield a posterior distribution. The interpretation of trial results is based on the posterior distribution and will vary as the prior distribution (i.e., the prior belief) varies. To aid in the interpretation of trial results, we also advocate the specification of a minimum clinically worthwhile treatment effect at the start of a trial. Conclusions and Implications: Our approach acknowledges that a number of different prior beliefs are possible, giving rise to a range of interpretations of results from a clinical trial. This approach provides a formal and systematic basis for considering both the range of likely opinions and the subsequent decision to be made with regard to the need for a confirmatory trial. We recommend that this approach be considered in the discussion of future confirmatory randomized clinical trials. C1 NCI,CANC THERAPY EVALUAT PROGRAM,CLIN INVEST BRANCH,BETHESDA,MD 20892. NCI,CANC THERAPY EVALUAT PROGRAM,BIOMETR RES BRANCH,BETHESDA,MD 20892. RP Parmar, MKB (reprint author), MRC,CANC TRIALS OFF,5 SHAFTESBURY RD,CAMBRIDGE,ENGLAND. NR 9 TC 41 Z9 41 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 20 PY 1996 VL 88 IS 22 BP 1645 EP 1651 DI 10.1093/jnci/88.22.1645 PG 7 WC Oncology SC Oncology GA VU793 UT WOS:A1996VU79300013 PM 8931608 ER PT J AU Merrill, RM Potosky, AL Feuer, EJ AF Merrill, RM Potosky, AL Feuer, EJ TI Changing trends in US prostate cancer incidence rates SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ANTIGEN; CARCINOMA RP Merrill, RM (reprint author), NCI,APPL RES BRANCH,DIV CANC PREVENT & CONTROL,NIH,EXECUT PLAZA N,RM 313,BETHESDA,MD 20892, USA. NR 15 TC 65 Z9 65 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 20 PY 1996 VL 88 IS 22 BP 1683 EP 1685 DI 10.1093/jnci/88.22.1683 PG 3 WC Oncology SC Oncology GA VU793 UT WOS:A1996VU79300019 PM 8931614 ER PT J AU Shi, B Stanfield, BB AF Shi, B Stanfield, BB TI Differential sprouting responses in axonal fiber systems in the dentate gyrus following lesions of the perforant path in Wld(s) mutant mice SO BRAIN RESEARCH LA English DT Article DE axonal sprouting; entorhinal cortex; hippocampus; mutant mouse; neuromorphological plasticity; septum ID SLOW WALLERIAN DEGENERATION; NERVE GROWTH-FACTOR; ADULT-RATS; ENTORHINAL CORTEX; C57BL/OLA MICE; HISTOCHEMICAL EVIDENCE; PERIPHERAL-NERVE; MOLECULAR LAYER; SENSORY AXONS; TIME COURSE AB Axons in both peripheral nerves and central fiber pathways undergo very slow Wallerian degeneration in Wld(s) mutant mice. It has recently been shown that in Wld(s) mutant mice there is a delay in the intensification of acetylcholinesterase histochemical staining in the molecular layer of the dentate gyrus following lesions of the entorhinal cortex [49]. Thus, it appears that delayed post-lesion reactive sprouting is associated with the delayed degeneration of cut central axons in this mutant. We have studied the time course of changes in the septohippocampal and the hippocampal commissural projections following interruption of perforant path in Wld(s) mutant mice and in normal (C57BL/6J) mice using the anterograde tracer, wheat germ agglutinin conjugated horseradish peroxidase. In normal mice, changes in the distribution of labeled septal and commissural axons indicative of sprouting are seen in the dentate molecular layer as early as 3 days post-lesion. The earliest survival time at which similar changes are found in Wld(s) mutant mice is seven days post-lesion, when an increase in the density of labeled septal axons begins in the outer molecular layer. The delay in the sprouting of commissural axons in the mutant is even longer. Changes in the distribution of labeled commissural axons in the dentate gyrus of Wld(s) mutant mice are first seen 12 days post-lesion. These results confirm that post-lesion reactive axonal sprouting can be delayed in the central nervous system of Wld(s) mutant mice. In addition, our results indicate that the extent of this delay may differ among axonal fiber systems. These findings are consistent with the notion that various central axonal systems may respond differentially to sprouting cues and are reminiscent of differences found in the regenerating response exhibited by sensory and motor axons in the Wld(s) mutant after peripheral nerve cuts [4,7,8,26]. C1 NIMH,NEUROPHYSIOL LAB,NIH,ANIM CTR,POOLESVILLE,MD 20837. NR 55 TC 12 Z9 12 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 NOV 18 PY 1996 VL 740 IS 1-2 BP 89 EP 101 DI 10.1016/S0006-8993(96)00849-9 PG 13 WC Neurosciences SC Neurosciences & Neurology GA VX994 UT WOS:A1996VX99400012 PM 8973802 ER PT J AU Bryngelson, JD Weiss, GH AF Bryngelson, JD Weiss, GH TI Polymers with internal length and displacement constraints: Bounds and exact expressions for free energies SO MACROMOLECULES LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; DISTANCE CONSTRAINTS; RUBBER ELASTICITY; RANDOM-WALKS; SOLID-STATE; MODEL; CONFIGURATIONS; MACROMOLECULES; MOLECULES AB Internal distance constraints in polymers often have a characteristic offset distance between the constrained monomers. This paper introduces a new kind of such constraint, the displacement constraint, which has particularly simple properties. The displacement constraint has both a characteristic offset distance and a characteristic offset direction. A simple, exact expression for the free energy of an ideal polymer with displacement constraints is derived. This expression is used to obtain bounds on the free energy of an ideal polymer with the more usual length constraints, which have a characteristic offset length but no characteristic direction. The form of these results suggest that the offset length can make an important contribution to the free energy if the offset distance is not negligible in comparison to the chemical distance between constrained monomers. RP Bryngelson, JD (reprint author), NIH, DIV COMP RES & TECHNOL, LAB PHYS SCI, BETHESDA, MD 20892 USA. NR 27 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0024-9297 EI 1520-5835 J9 MACROMOLECULES JI Macromolecules PD NOV 18 PY 1996 VL 29 IS 24 BP 7995 EP 7999 DI 10.1021/ma960790q PG 5 WC Polymer Science SC Polymer Science GA VU066 UT WOS:A1996VU06600044 ER PT J AU Alavanja, MCR Brownson, RC Berger, E Lubin, J Modigh, C AF Alavanja, MCR Brownson, RC Berger, E Lubin, J Modigh, C TI Avian exposure acid risk of lung cancer in women in Missouri: Population based case-control study SO BRITISH MEDICAL JOURNAL LA English DT Article ID NONSMOKING WOMEN; UNITED-STATES; PET BIRDS AB Objective-To investigate the association, previously reported in three European studies, between ownership of pet birds and the risk of lung cancer. Design-A population based case-control study with a structured questionnaire administered by telephone. Setting-Missouri, a midwestern state in the United States with a population of about 5 million. Subjects-All newly diagnosed cases of primary lung cancer in women aged 30-84 years in Missouri from 1 January 1993 to 31 January 1994 reported to the state cancer registry were invited to participate (n = 652); and 629 population based controls. Main outcome measures-Odds ratios were computed in relation to whether or not the study subject ever kept pet birds, the type of bird kept, and several measures of intensity or duration of exposure. Odds ratios were adjusted for smoking. Results-The odds ratio (95% confidence interval) for the development of lung cancer associated with keeping pet birds was 0.84 (0.65 to 1.09). The results were similar for the type of pet bird kept, the number of birds kept, the location of the bird in the house, and the duration of ownership. Conclusion-The keeping of pet birds carries no excess risk for the development of lung cancer. C1 ST LOUIS UNIV,SCH PUBL HLTH,DEPT COMMUNITY MED,ST LOUIS,MO 63108. INFORMAT MANAGEMENT SERV INC,ROCKVILLE,MD 20904. GOTHENBURG UNIV,GOTHENBURG,SWEDEN. RP Alavanja, MCR (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,DIV CANC EPIDEMIOL & GENET,EXECUT PLAZA N,ROOM 430,ROCKVILLE,MD 20852, USA. FU NCI NIH HHS [CP-95654-13] NR 19 TC 17 Z9 17 U1 0 U2 4 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD NOV 16 PY 1996 VL 313 IS 7067 BP 1233 EP 1235 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA VU208 UT WOS:A1996VU20800020 PM 8939111 ER PT J AU Modigh, C Axelsson, G Alavanja, M Andersson, L Rylander, R AF Modigh, C Axelsson, G Alavanja, M Andersson, L Rylander, R TI Pet birds and risk of lung cancer in Sweden: A case-control study SO BRITISH MEDICAL JOURNAL LA English DT Article ID NONSMOKING WOMEN AB Objective-To investigate the association between keeping birds and the risk of lung cancer in Sweden. Design-Case-control study based on cases of lung cancer and community controls. Interviews were performed by two nurses specially trained for this project. Setting-Three major referral hospitals located in southwest Sweden. Subjects-All patients aged 75 and under with newly diagnosed lung cancer and of Scandinavian birth who lived in one of 26 municipalities in Gothenburg and Bohus county or Alvsborg county. Potential control subjects matched on county of residence, sex, and closest date of birth were selected from population registries. In the context of a larger case-control study, information on pet birds was obtained from 380 patients with lung cancer (252 men) and 696 controls (433 men). Main outcome measures-Odds ratios for lung cancer in relation to whether or not pet birds were kept and the duration of keeping pet birds. Results-The adjusted odds ratio for ever versus never exposed to pet birds at home was 0.94 (95% confidence interval 0.64 to 1.39) for men and 1.10 (0.64 to 1.90) for women. There was no evidence of a trend for increased risk of lung cancer with duration of bird ownership. Conclusion-Bird keeping does not seem to confer any excess risk of lung cancer to Swedish men or women. C1 NCI, DIV CANC EPIDEMIOL & GENET, ROCKVILLE, MD 20852 USA. N ALVSBORG GEN HOSP, LUNG CLIN, TROLLHATTAN, SWEDEN. RP Modigh, C (reprint author), GOTHENBURG UNIV, DEPT ENVIRONM MED, MEDICINAREGATAN 16, S-41390 GOTHENBURG, SWEDEN. NR 18 TC 12 Z9 12 U1 1 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD NOV 16 PY 1996 VL 313 IS 7067 BP 1236 EP 1238 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA VU208 UT WOS:A1996VU20800021 PM 8939112 ER PT J AU Vinetz, JM Glass, GE Flexner, CE Mueller, P Kaslow, DC AF Vinetz, JM Glass, GE Flexner, CE Mueller, P Kaslow, DC TI Sporadic urban leptospirosis SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE Leptospira interrogans; leptospirosis; urban population; rats; polymerase chain reaction ID RISK-FACTORS; ROCHALIMAEA AB Background: Surprisingly, many inner-city residents have antibodies to Leptospira interrogans. The manner in which these persons acquire this organism in the absence of recognized occupational, recreational, or epidemic risk factors is not known. Objective: To study the epidemiology of patients with leptospirosis who acquired L. interrogans in inner-city Baltimore, Maryland. Design: Epidemiologic investigation. Setting: Inner-city university hospital. Patients: Three inner-city residents who developed leptospirosis. Measurements: Trapping rats in alleys where the patients may have acquired L. interrogans; polymerase chain reaction (PCR) analysis of patient serum and cerebrospinal fluid specimens and rat tissues to determine the presence of leptospiral DNA; and serologic testing of serum from patients and rats by microagglutination assay to confirm L. interrogans infection. Results: Three patients developed leptospirosis after probable percutaneous exposure to rat (Rattus norvegicus) urine in Baltimore alleys. A PCR assay detected L. interrogans DNA in samples of body fluid obtained from the first two patients at presentation (one in cerebrospinal fluid, the other in serum). Results of PCR done on serum drawn from the third patient after antibiotic therapy began were negative. A microagglutination test showed that all patients had high levels of antibodies to the L. interrogans serogroup Icterohaemorrhagiae. In 19 of 21 rats that were trapped in the alleys where the patients had sustained lacerations before illness developed, kidney or brain tissues were positive by PCR for the presence of L. interrogans. Conclusions: A population was discovered to be at risk for acquiring L. interrogans: urban residents who are sporadically exposed to rat urine in the inner city. Inner-city rats often carry L. interrogans. Polymerase chain reaction can quickly establish the diagnosis of leptospirosis and is useful for epidemiologic study. An endemic substrate for the transmission of the organism is present in inner-city Baltimore. Leptospirosis may become increasingly recognized in deteriorating inner cities in which rat populations are expanding. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MOL MICROBIOL & IMMUNOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21287. NIH,BETHESDA,MD 20892. RP Vinetz, JM (reprint author), NIAID,PARASIT DIS LAB,9000 ROCKVILLE PIKE,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. OI Vinetz, Joseph/0000-0001-8344-2004 NR 22 TC 139 Z9 143 U1 3 U2 15 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 NOV 15 PY 1996 VL 125 IS 10 BP 794 EP & PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA VU524 UT WOS:A1996VU52400005 PM 8928985 ER PT J AU Curtis, JF Reddy, NG Mason, RP Kalyanaraman, B Eling, TE AF Curtis, JF Reddy, NG Mason, RP Kalyanaraman, B Eling, TE TI Nitric oxide: A prostaglandin H synthase 1 and 2 reducing cosubstrate that does not stimulate cyclooxygenase activity or prostaglandin H synthase expression in murine macrophages SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID ARACHIDONIC-ACID; GUANYLATE-CYCLASE; ACTIVATION; PEROXIDASE; MECHANISM; REDUCTION; CELLS; LIPOPOLYSACCHARIDE; INFLAMMATION; BIOSYNTHESIS AB Several recent reports have investigated the possibility that nitric oxide ((NO)-N-.) can regulate prostaglandin H synthase (PHS) activity, The potential significance of (NO)-N-. regulation of PHS is considerable, when one considers the numerous important biological processes that are influenced by PHS. In this study, we used microsomal and purified PHS to investigate the direct effect of (NO)-N-. and (NO)-N-.-generating compounds on PHS catalytic activity. We found that (NO)-N-. neither significantly inhibited nor enhanced prostaglandin (PG) formation, despite the fact that (NO)-N-. stimulated PHS peroxidase activity. We also investigated the effect of (NO)-N-. and (NO)-N-. generators on PHS product, protein, and mRNA levels in the RAW264.7 murine macrophage cell line. We found that (NO)-N-. or (NO)-N-. generators had little or no effect on PG formation, PHS expression, or PHS mRNA expression in unstimulated RAW264.7 cells. The same results were obtained with macrophages that were stimulated by 18 h pretreatment with lipopolysaccharide, a known inducer of PHS-2 in macrophages. These data clearly indicate that (NO)-N-. acts as a cosubstrate for PHS peroxidase. However, (NO)-N-. does not enhance or inhibit either cycloxygenase activity or expression of PHS in the model systems used in this study. (C) 1996 Academic Press, Inc. C1 NIEHS,RES TRIANGLE PK,NC 27709. MED COLL WISCONSIN,MILWAUKEE,WI 53226. NR 41 TC 57 Z9 57 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 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD NOV 15 PY 1996 VL 335 IS 2 BP 369 EP 376 DI 10.1006/abbi.1996.0518 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VV311 UT WOS:A1996VV31100015 PM 8914934 ER PT J AU Jaworski, C Wistow, G AF Jaworski, C Wistow, G TI LP2, a differentiation-associated lipid-binding protein expressed in bovine lens SO BIOCHEMICAL JOURNAL LA English DT Article ID FATTY-ACID-BINDING; EPITHELIAL-CELLS; MESSENGER-RNA; GROWTH-FACTOR; TERMINAL DIFFERENTIATION; EYE LENS; INSULIN; IDENTIFICATION; EVOLUTION; INHIBITOR AB A 13 kDa protein from bovine lens was identified and characterized by protein microsequencing and by rapid amplification of cDNA ends (RACE) PCR. Its complete sequence shows that this protein belongs to a family of fatty acid-binding proteins (FABPs), including myelin and adipocyte P2, that are associated with cellular differentiation. The bovine lens protein, designated LP2, shows very close similarity to human epidermal FABP (eFABP) and human eFABP was detected in human lens, suggesting that the two proteins might be orthologous. Reverse transcriptase-PCR (RT-PCR) was used to compare expression patterns of LP2 with those for actin and for the differentiation markers gamma B-crystallin and gamma s-crystallin in lens. Actin was most abundant in the relatively undifferentiated epithelial cells and decreased with lens cell differentiation. In contrast gamma B-crystallin and gamma s-crystallin were detected only in fibres (nuclear and cortical respectively). LP2 transcripts were detected most abundantly in fibre cells and apparently increased with cellular differentiation. Molecular modelling confirms that the sequence of LP2 fits the tertiary template of adipocyte P2 but reveals the presence of two close pairs of cysteine residues that might be susceptible to intramolecular disulphide bond formation under appropriate oxidizing conditions. LP2 is thus another potential target for oxidative stress during cataract formation in lens. C1 NEI, MOL & DEV BIOL LAB, SECT MOL STRUCT & FUNCT, NIH, BETHESDA, MD 20892 USA. NR 41 TC 33 Z9 34 U1 0 U2 1 PU PORTLAND PRESS LTD PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND SN 0264-6021 EI 1470-8728 J9 BIOCHEM J JI Biochem. J. PD NOV 15 PY 1996 VL 320 BP 49 EP 54 PN 1 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VU845 UT WOS:A1996VU84500008 PM 8947466 ER PT J AU Hansen, HJ Ong, GL Diril, H Valdez, A Roche, PA Griffiths, GL Goldenberg, DM Mattes, MJ AF Hansen, HJ Ong, GL Diril, H Valdez, A Roche, PA Griffiths, GL Goldenberg, DM Mattes, MJ TI Internalization and catabolism of radiolabelled antibodies to the MHC class-II invariant chain by B-cell lymphomas SO BIOCHEMICAL JOURNAL LA English DT Article ID RECEPTOR-MEDIATED ENDOCYTOSIS; MONOCLONAL-ANTIBODIES; SURFACE EXPRESSION; LYMPHOCYTES; TRANSPORT; COMPLEXES; ANTIGENS; MALIGNANCIES; COMPARTMENT; DEGRADATION AB The fate of antibody (Ab) LL1, which reacts with the invariant chain (Ii) subunit of the immature MHC class-II antigen (CD74) after binding to the surface of B-cell lymphomas was investigated. This Ab was internalized and catabolized very rapidly, much faster than other Abs that are considered to be rapidly internalized, such as CD19, CD22 and anti-(transferrin receptor). Such internalization did not depend on Ab cross-linking. The capacity of this uptake process was determined in long-term experiments by increasing the Ab concentration:in 1 day, approx. 8 x 10(6) Ab molecules per cell were catabolized. This analysis was facilitated by the use of radiolabels that are trapped within cells after catabolism of the Abs to which they were conjugated. If the Ab is a reliable marker for the Ii antigen, which is likely, we can conclude that Ii directed to the cell surface appears to be sufficient, indeed more than sufficient, to account for the cell content of mature class-II molecules. C1 CTR MOL MED & IMMUNOL,GARDEN STATE CANC CTR,NEWARK,NJ 07103. IMMUNOMED INC,MORRIS PLAINS,NJ 07950. NCI,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [CA63624]; NCRR NIH HHS [RR05903] NR 40 TC 69 Z9 70 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 NOV 15 PY 1996 VL 320 BP 293 EP 300 PN 1 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VU845 UT WOS:A1996VU84500042 PM 8947500 ER PT J AU Sloand, E Kessler, C Maciejewski, J Kirby, M Sato, T AF Sloand, E Kessler, C Maciejewski, J Kirby, M Sato, T TI Von Willebrand factor preferentially binds to erythrocytes of patients with sickle cell anemia (SCA) and paroxysmal hemoglobinuria (PNH). SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,MED CTR,DIV HEMATOL ONCOL,WASHINGTON,DC 20037. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 14 EP 14 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300014 ER PT J AU Alpan, O Sillard, R Parker, RI AF Alpan, O Sillard, R Parker, RI TI Na,K-ATPase mediated inhibition of platelet aggregation. SO BLOOD LA English DT Meeting Abstract C1 NIAID,NIH,BETHESDA,MD 20892. KAROLINSKA INST,DEPT MED BIOCHEM & BIOPHYS,STOCKHOLM,SWEDEN. SUNY STONY BROOK,DEPT PEDIAT,STONY BROOK,NY 11794. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 98 EP 98 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300098 ER PT J AU Sato, T Selleri, C Maciejewski, JP Young, NS AF Sato, T Selleri, C Maciejewski, JP Young, NS TI IFN-gamma's negative and positive effects on human hematopoietic cells role of STAT1/STAT3 phosphorylation AND IRF-1 induction. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. YOKOHAMA ROSAI HOSP,DEPT MED,YOKOHAMA,KANAGAWA,JAPAN. NR 0 TC 0 Z9 0 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 NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 187 EP 187 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300187 ER PT J AU Murphy, WJ Asai, O Hirano, A Funakoshi, S Fanslow, WC Longo, DL AF Murphy, WJ Asai, O Hirano, A Funakoshi, S Fanslow, WC Longo, DL TI Inhibition of aggressive histology human B cell lymphoma growth by CD40 stimulation in vivo: A comparison of a CD40 antibody and a recombinant soluble CD40 ligand (srCD40L). SO BLOOD LA English DT Meeting Abstract C1 NCI,DBS,LLB,FREDERICK,MD 21701. FCRDC,IRSP,SAIC,FREDERICK,MD. IMMUNEX CORP,SEATTLE,WA. NIA,BALTIMORE,MD 21224. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 343 EP 343 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300343 ER PT J AU Williams, ME Rogers, MJ Daggett, JL Bergsagel, PL Kuehl, M Bender, T AF Williams, ME Rogers, MJ Daggett, JL Bergsagel, PL Kuehl, M Bender, T TI Frequent deletion of the cyclin dependent kinase inhibitor genes p16 and p18 in human multiple myeloma cell lines. SO BLOOD LA English DT Meeting Abstract C1 UNIV VIRGINIA,SCH MED,CHARLOTTESVILLE,VA 22908. NCI,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 398 EP 398 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300398 ER PT J AU Maass, G Bogedain, C Wendtner, CM Scheer, U Volkenandt, M Michl, D BarunFalco, M Emmerich, B Kotin, R Winnacker, EL Hallek, M AF Maass, G Bogedain, C Wendtner, CM Scheer, U Volkenandt, M Michl, D BarunFalco, M Emmerich, B Kotin, R Winnacker, EL Hallek, M TI Highly efficient ex vivo gene transfer into primary human tumor cells using improved recombinant adeno-associated virus (rAAV) vectors. SO BLOOD LA English DT Meeting Abstract C1 UNIV MUNICH,GENZENTRUM,MED KLIN,D-8000 MUNICH,GERMANY. UNIV MUNICH,DERMATOL KLIN,D-8000 MUNICH,GERMANY. MEDIGENE GMBH,MARTINSRIED,GERMANY. NHLBI,NIH,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 526 EP 526 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300526 ER PT J AU Hoshino, T Jiang, YZ Dunn, D Wang, J Barrett, AJ Liu, JM AF Hoshino, T Jiang, YZ Dunn, D Wang, J Barrett, AJ Liu, JM TI Transfection of interleukin-12 cDNAs into tumor cells enhances cytotoxic responses against native tumor. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 534 EP 534 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300534 ER PT J AU Wiener, SM Liu, YJ Shors, S Smith, RH Chiorini, J Kilcoin, N Kotin, RM Safer, B AF Wiener, SM Liu, YJ Shors, S Smith, RH Chiorini, J Kilcoin, N Kotin, RM Safer, B TI Stable production in vitro of human coagulation factor IX expressed from adeno-associated virus. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,MOL HEMATOL BRANCH,NIH,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 541 EP 541 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300541 ER PT J AU Lozier, JN Yankaskas, JR Morgan, RA AF Lozier, JN Yankaskas, JR Morgan, RA TI Polarized secretion of recombinant FVIII and FIX by transduced gut epithelial cells: Implications for gene therapy of hemophilia. SO BLOOD LA English DT Meeting Abstract C1 UNIV N CAROLINA,DIV PULM MED,CHAPEL HILL,NC. NIH,CLIN GENE THERAPY BRANCH,BETHESDA,MD. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 542 EP 542 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300542 ER PT J AU Wang, J Youssoufian, H LotenFoe, JR Devetten, M Cumming, RC Buchwald, M Liu, JM AF Wang, J Youssoufian, H LotenFoe, JR Devetten, M Cumming, RC Buchwald, M Liu, JM TI Overexpression of the Fanconi anemia group C gene (FAC) protects hematopoietic progenitors from Fas-mediated apoptosis. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. FREE UNIV AMSTERDAM,NL-1081 HV AMSTERDAM,NETHERLANDS. HOSP SICK CHILDREN,TORONTO,ON M5G 1X8,CANADA. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 548 EP 548 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300548 ER PT J AU Li, J Noguchi, CT Schechter, AN AF Li, J Noguchi, CT Schechter, AN TI Multiple negative regulatory elements control the expression of the human epsilon globin gene. SO BLOOD LA English DT Meeting Abstract C1 NIDDK,BIOL CHEM LAB,NIH,BETHESDA,MD. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 584 EP 584 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300584 ER PT J AU Ikonomi, P Noguchi, CT Schechter, AN AF Ikonomi, P Noguchi, CT Schechter, AN TI GATA-1 participates in the silencing of the epsilon globin gene. SO BLOOD LA English DT Meeting Abstract C1 NIDDK,BIOL CHEM LAB,NIH,BETHESDA,MD. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 585 EP 585 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300585 ER PT J AU Park, JI Han, JY Rodgers, GP Kim, LH AF Park, JI Han, JY Rodgers, GP Kim, LH TI The region between -240 and -269 of gamma-globin gene promoter is responsible for gamma-globin gene augmentation by hydroxyurea. SO BLOOD LA English DT Meeting Abstract C1 DONG A UNIV,COLL MED,CLIN MED RES INST,PUSAN,SOUTH KOREA. NIDDK,MOL HEMATOL UNIT,NIH,BETHESDA,MD. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 596 EP 596 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300596 ER PT J AU Han, JY Park, JI Kim, JM Bae, HR Lee, YH Fibach, E Rodgers, GP Kim, IH AF Han, JY Park, JI Kim, JM Bae, HR Lee, YH Fibach, E Rodgers, GP Kim, IH TI Transcriptional control mechanisms in enhancement of Hb F by hemin or hydroxyurea are different between adult and cord blood erythroid cells. SO BLOOD LA English DT Meeting Abstract C1 DONG A UNIV,COLL MED,CLIN MED RES INST,PUSAN,SOUTH KOREA. NIDDK,MOL HEMATOL UNIT,NIH,BETHESDA,MD. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 597 EP 597 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300597 ER PT J AU Tang, DC Fucharoen, S Ding, I Rodgers, GP AF Tang, DC Fucharoen, S Ding, I Rodgers, GP TI Simplified PCR method to diagnose and differentiate the five common alpha-thalassemia genotypes. SO BLOOD LA English DT Meeting Abstract C1 MAHIDOL UNIV,BANGKOK 10700,THAILAND. NIDDK,MOL HEMATOL SECT,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 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 NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 600 EP 600 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300600 ER PT J AU Ding, I Neta, R Shin, Y Li, A McGrady, G Wahl, S Okuniefff, P AF Ding, I Neta, R Shin, Y Li, A McGrady, G Wahl, S Okuniefff, P TI TGF-B1 knockout mice as a model in radiation-induced fibrosis. SO BLOOD LA English DT Meeting Abstract C1 NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NIDR,IMMUNOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 615 EP 615 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300615 ER PT J AU Emmons, RVB Gogineni, MA Metzger, M Donahue, R Young, NS Dunbar, CE AF Emmons, RVB Gogineni, MA Metzger, M Donahue, R Young, NS Dunbar, CE TI Suppression of primate hematopoiesis by administration of retrovirally-modified gamma-interferon-expressing stromal cells. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 735 EP 735 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300735 ER PT J AU Miller, JL Giattina, MR AF Miller, JL Giattina, MR TI Membrane xenografting of CD4 permits syncytia formation. SO BLOOD LA English DT Meeting Abstract C1 NIDDK,BIOL CHEM LAB,NIH,BETHESDA,MD. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 747 EP 747 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300747 ER PT J AU Pope, SH Fibach, E Kim, HJ Rodgers, GP AF Pope, SH Fibach, E Kim, HJ Rodgers, GP TI Kinetics of expression of genes for globins, transcription factors and cytokine receptors during maturation of adult normal human erythroid cells. SO BLOOD LA English DT Meeting Abstract C1 NIDDK,BIOL CHEM LAB,NIH,BETHESDA,MD. HADASSAH UNIV HOSP,DEPT HEMATOL,IL-91120 JERUSALEM,ISRAEL. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 750 EP 750 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300750 ER PT J AU Liu, C Liu, ZY Noguchi, CT AF Liu, C Liu, ZY Noguchi, CT TI Appropriate expression of the human erythropoietin receptor in transgenic mice. SO BLOOD LA English DT Meeting Abstract C1 NIDDK,BIOL CHEM LAB,NIH,BETHESDA,MD. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 759 EP 759 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300759 ER PT J AU Blair, DG Athanasiou, M Watson, D Clausen, P AF Blair, DG Athanasiou, M Watson, D Clausen, P TI Evidence that specific members of the ETS family of transcription factors function in a lineage-specific fashion in erythroid and megakaryocyte differentiation. SO BLOOD LA English DT Meeting Abstract C1 NCI,NIH,DBS,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,FREDERICK,MD. MUSC,CHARLESTON,SC. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 761 EP 761 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300761 ER PT J AU Laprise, SL Orlic, D Girard, LJ Bodine, DM AF Laprise, SL Orlic, D Girard, LJ Bodine, DM TI Identification of differentially expressed partial gene transcripts in primitive murine hematopoietic stem cell populations SO BLOOD LA English DT Meeting Abstract C1 NIH,HEMATOPOIESIS SECT,LGT,NCHGR,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 763 EP 763 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300763 ER PT J AU Gutierrez, MI Raj, A Spangler, G Guerrero, I Judde, JG Magrath, I Bhatia, K AF Gutierrez, MI Raj, A Spangler, G Guerrero, I Judde, JG Magrath, I Bhatia, K TI Sequence variations in EBNA-1 specific for B or T cell lymphomas may underlie the pathogenetic role of EBV in lymphomagenesis. SO BLOOD LA English DT Meeting Abstract C1 NCI,LYMPHONA BIOL SECT,PEDIAT ONCOL BRANCH,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 823 EP 823 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300823 ER PT J AU Haddy, TB Adde, MA Magrath, IT AF Haddy, TB Adde, MA Magrath, IT TI Prospects for long term survival with minimal late effects in young patients with high grade non-Hodgkin's lymphomas. SO BLOOD LA English DT Meeting Abstract C1 NCI,PEDIAT ONCOL BRANCH,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 882 EP 882 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300882 ER PT J AU Selleri, C Sato, T DelVecchio, L Luciano, L Barrett, AJ Rotoli, B Young, NS Maciejewski, JP AF Selleri, C Sato, T DelVecchio, L Luciano, L Barrett, AJ Rotoli, B Young, NS Maciejewski, JP TI Involvement of Fas-mediated apoptosis in the inhibitory effects of interferon-alpha in chronic myelogenous leukemia. SO BLOOD LA English DT Meeting Abstract C1 UNIV NAPLES FEDERICO II,SCH MED,DIV HEMATOL,NAPLES,ITALY. CARDARELLI HOSP,SERV IMMUNOHEMATOL,NAPLES,ITALY. NHLBI,HEMATOL BRANCH,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 914 EP 914 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300914 ER PT J AU Shahidi, H Gregory, SA Stratakis, CA Vottero, A Kino, T Karl, M Chrousos, GP Plate, JMD AF Shahidi, H Gregory, SA Stratakis, CA Vottero, A Kino, T Karl, M Chrousos, GP Plate, JMD TI Glucocorticoid-induced apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) associated with the syndrome of glucocorticoid resistance. SO BLOOD LA English DT Meeting Abstract C1 RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. NIHHD,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 935 EP 935 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300935 ER PT J AU Jiang, YZ Mayroudis, DA Dermine, S Molldrem, J Hensel, N Barrett, AJ AF Jiang, YZ Mayroudis, DA Dermine, S Molldrem, J Hensel, N Barrett, AJ TI Limited use of T cell receptor (TCR) V beta by allogeneic T cells responding to chronic myelogenous leukemia (CML): Implications for specifically enhancing the graft-versus-leukemia (GVL) effect. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,BONE MARROW TRANSPLANT UNIT,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. RI Dermime, Said/C-6235-2009 OI Dermime, Said/0000-0002-5526-7496 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 962 EP 962 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300962 ER PT J AU Asai, O Longo, DL Ruscetti, FW Murphy, WJ AF Asai, O Longo, DL Ruscetti, FW Murphy, WJ TI Prevention of graft-versus-host disease by IL-2 activated donor NK cells after allogeneic bone marrow transplantation in mice, role of IL-2. SO BLOOD LA English DT Meeting Abstract C1 NCI,DBS,FREDERICK,MD 21701. NCI,FCRDC,SAIC FREDERICK,IRSP,FREDERICK,MD 21701. NIA,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 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 NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 978 EP 978 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98300978 ER PT J AU Mayroudis, D Read, EJ Vigue, F Chau, Q Carter, C Leitman, S Molldrem, J Emde, M Berninger, R Risdon, G AnditoreHargreaves, K Barrett, AL AF Mayroudis, D Read, EJ Vigue, F Chau, Q Carter, C Leitman, S Molldrem, J Emde, M Berninger, R Risdon, G AnditoreHargreaves, K Barrett, AL TI T cell depletion of C-CSF mobilized peripheral blood progenitor cells from normal donors. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BMT UNIT,BETHESDA,MD 20892. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. CELLPRO INC,BOTHELL,WA. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1004 EP 1004 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301004 ER PT J AU Mayroudis, D Dermime, S Jiang, YZ Molldrem, J Hensel, N Fellowes, Y Raptis, A Barrett, AJ AF Mayroudis, D Dermime, S Jiang, YZ Molldrem, J Hensel, N Fellowes, Y Raptis, A Barrett, AJ TI Selective immunodepletion between HLA matched siblings that reduces the risk for GVHD and preserves reactivity against the leukemia and Epstein-Barr virus SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BMT UNIT,BETHESDA,MD 20892. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. RI Dermime, Said/C-6235-2009 OI Dermime, Said/0000-0002-5526-7496 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1005 EP 1005 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301005 ER PT J AU Risdon, G Read, EJ Potter, M Kanz, L AuditoreHargreaves, K AF Risdon, G Read, EJ Potter, M Kanz, L AuditoreHargreaves, K TI Pan T-cell depletion of PBSC: Allograft engineering with the CEPRATE TCD system. SO BLOOD LA English DT Meeting Abstract C1 ROYAL HOSP SICK CHILDREN,BMT UNIT,BRISTOL BS2 8BJ,AVON,ENGLAND. NHLBI,BETHESDA,MD 20892. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. UNIV TUBINGEN,TUBINGEN,GERMANY. CELLPRO INC,BOTHELL,WA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1006 EP 1006 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301006 ER PT J AU Barrett, AJ Mavroudis, D Molldrem, J Couriel, D Young, NS AF Barrett, AJ Mavroudis, D Molldrem, J Couriel, D Young, NS TI Immune modulation to treat leukemic relapse following allogeneic bone marrow transplantation: A risk-based sequential approach. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BMT UNIT,NIH,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1026 EP 1026 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301026 ER PT J AU Flake, AW Roncarolo, MG Puck, JM AlmeidaPorada, G Zanjani, ED AF Flake, AW Roncarolo, MG Puck, JM AlmeidaPorada, G Zanjani, ED TI Persistence of engraftment and documentation of donor derived CD34+/CD38 cells in the recipient bone marrow after in utero transplantation for X-linked severe combined immunodeficiency. SO BLOOD LA English DT Meeting Abstract C1 DNAX RES INST MOL & CELLULAR BIOL INC,PALO ALTO,CA 94304. CHILDRENS HOSP PHILADELPHIA,DEPT SURG,PHILADELPHIA,PA 19104. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. UNIV NEVADA,VET ADM MED CTR,RENO,NV 89557. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1054 EP 1054 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301054 ER PT J AU Porada, CD Tran, N Moen, R Troutman, L Flake, AW Eglitis, M Anderson, WF Zanjani, ED AF Porada, CD Tran, N Moen, R Troutman, L Flake, AW Eglitis, M Anderson, WF Zanjani, ED TI In utero gene therapy in sheep. SO BLOOD LA English DT Meeting Abstract C1 UNIV SO CALIF,LOS ANGELES,CA. NIH,BETHESDA,MD 20892. UNIV MICHIGAN,DETROIT,MI. UNIV NEVADA,VAMC,RENO,NV 89557. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1071 EP 1071 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301071 ER PT J AU Tiberghien, P Cahn, JY Millpied, N Ferrand, C Deconinck, E Brion, A Reynolds, CW Jacob, W Certoux, JM Chiang, Y Herve, P AF Tiberghien, P Cahn, JY Millpied, N Ferrand, C Deconinck, E Brion, A Reynolds, CW Jacob, W Certoux, JM Chiang, Y Herve, P TI Administration of donor T-cells expressing the herpes-simplex thymidine-kinase gene in conjunction with a T-cell depleted allogeneic marrow graft. SO BLOOD LA English DT Meeting Abstract C1 CHU BESANCON,SERV HEMATOL,ETS FRANCHE COMTE,F-25030 BESANCON,FRANCE. CHU NANTES,SERV HEMATOL,F-44035 NANTES 01,FRANCE. GENET THERAPY INC,GAITHERSBURG,MD. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1077 EP 1077 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301077 ER PT J AU Whitwam, T Seidel, NE Haskins, ME Anderson, SM Henthorn, PS Bodine, DM Puck, JM AF Whitwam, T Seidel, NE Haskins, ME Anderson, SM Henthorn, PS Bodine, DM Puck, JM TI Marking of canine hematopoietic progenitors in cytokine stimulated bone marrow with retroviruses containing the IL2RG gene. SO BLOOD LA English DT Meeting Abstract C1 UNIV PENN,SCH VET MED,PHILADELPHIA,PA 19104. NIH,NATL CTR HUMAN GENOME RES,LAB GENE TRANSFER,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1089 EP 1089 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301089 ER PT J AU Wang, Q Stacy, T Miller, JD Lewis, AF Gu, TL Huang, X Bushweller, JH Bories, JC Alt, FW Ryan, G Liu, PP WynshawBoris, A Binder, M MarinPadilla, M Sharpe, AH Speck, NA AF Wang, Q Stacy, T Miller, JD Lewis, AF Gu, TL Huang, X Bushweller, JH Bories, JC Alt, FW Ryan, G Liu, PP WynshawBoris, A Binder, M MarinPadilla, M Sharpe, AH Speck, NA TI The core-binding factor (CBF) beta subunit is essential for CBF alpha 2 (AML1) function in vivo. SO BLOOD LA English DT Meeting Abstract C1 DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,HANOVER,NH 03756. CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1147 EP 1147 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301147 ER PT J AU Castilla, LH Wijmenga, C Wang, Q Speck, NA Collins, FS WynshawBoris, A Liu, PP AF Castilla, LH Wijmenga, C Wang, Q Speck, NA Collins, FS WynshawBoris, A Liu, PP TI Germline transmission of the leukemia fusion gene CBFB-MYH11 causes blockage of definitive hematopoiesis and embryonic lethal hemorrhage in heterozygous (Cbfb-MYH11 +/-) embryos SO BLOOD LA English DT Meeting Abstract C1 NIH,NATL CTR HUMAN GENOME RES,LAB GENE TRANSFER,BETHESDA,MD 20892. NIH,NATL CTR HUMAN GENOME RES,LAB GENET DIS RES,BETHESDA,MD 20892. DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,DEPT BIOCHEM,HANOVER,NH 03756. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1149 EP 1149 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301149 ER PT J AU Tisdale, JF Sellers, SE Agricola, BA Donahue, RE Dunbar, CE AF Tisdale, JF Sellers, SE Agricola, BA Donahue, RE Dunbar, CE TI Gene marking studies indicate that ex-vivo expansion of mobilized rhesus peripheral blood cells results in rapid initial engraftment but diminished long term repopulating ability. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,NIH,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1188 EP 1188 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301188 ER PT J AU Bloom, ML SimonStoos, KL AF Bloom, ML SimonStoos, KL TI Progenitor and stem cell analysis of the hemoglobin deficit mouse reveals a defect in the early erythroid lineage. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1201 EP 1201 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301201 ER PT J AU Brown, KE Tisdale, J Dunbar, CE Barrett, AJ Young, NS AF Brown, KE Tisdale, J Dunbar, CE Barrett, AJ Young, NS TI Hepatitis/aplastic anemia: An immuno-mediated disease of unknown viral (?) etiology SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1225 EP 1225 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301225 ER PT J AU Leitman, SF Oblitas, JM Emmons, R Dunn, DE Young, NS AF Leitman, SF Oblitas, JM Emmons, R Dunn, DE Young, NS TI Clinical efficacy of daily G-CSF-recruited granulocyte transfusions in patients with severe neutropenia and life-threatening infections. SO BLOOD LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NHLBI,NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 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 NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1313 EP 1313 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301313 ER PT J AU Sato, T Kim, S Selleri, C Young, NS Maciejewski, JP AF Sato, T Kim, S Selleri, C Young, NS Maciejewski, JP TI Determination of LTC-IC numbers in patients with myelodysplastic syndromes. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1338 EP 1338 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301338 ER PT J AU Selleri, C Sato, T Raiola, A Rotoli, B Young, NS Maciejewski, JP AF Selleri, C Sato, T Raiola, A Rotoli, B Young, NS Maciejewski, JP TI Induction of nitric oxide synthase in Fas-mediated apoptosis in hematopoietic cells. SO BLOOD LA English DT Meeting Abstract C1 UNIV NAPLES FEDERICO II,DIV HEMATOL,NAPLES,ITALY. NHLBI,HEMATOL BRANCH,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1361 EP 1361 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301361 ER PT J AU Hirano, A Asai, O Funakoshi, S Longo, D Murphy, W AF Hirano, A Asai, O Funakoshi, S Longo, D Murphy, W TI Effects of CD40 stimulation on human and murine hematopoiesis. SO BLOOD LA English DT Meeting Abstract C1 NCI,DBS,LLB,FREDERICK,MD 21701. IMMUNEX CORP,SEATTLE,WA. NIA,BALTIMORE,MD 21224. SAIC,IRSP,FREDERICK,MD. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1370 EP 1370 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301370 ER PT J AU Bendandi, M Kobrin, CB Grove, SB Kwak, LW AF Bendandi, M Kobrin, CB Grove, SB Kwak, LW TI Identification of Ig heavy chain gene rearrangements derived from human follicular lymphomas and corresponding somatic cell hybrids producing idiotypic vaccines. SO BLOOD LA English DT Meeting Abstract C1 NCI,DIV CLIN SCI,FREDERICK,MD 21701. SAIC,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1525 EP 1525 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301525 ER PT J AU Detrick, B Hooks, JJ Keiser, J Tabbara, I AF Detrick, B Hooks, JJ Keiser, J Tabbara, I TI Detection of cytomegalovirus (CMV) proteins in hematopoietic stem cell transplantation (HSCT) patients by flow cytometry. SO BLOOD LA English DT Meeting Abstract C1 GEORGE WASHINGTON UNIV,SCH MED,WASHINGTON,DC. NEI,NIH,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1687 EP 1687 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301687 ER PT J AU Braun, SE Mantel, C Hromas, R Cooper, S Robertson, K Deng, C Broxmeyer, HE AF Braun, SE Mantel, C Hromas, R Cooper, S Robertson, K Deng, C Broxmeyer, HE TI Correction of hematopoietic colony formation deficiency in cells of p21(cip1) knockout mice and enhancement of colony formation from cells of normal mice by retroviral-mediated gene transfer of p21(cip1) into bone marrow progenitor cells in vitro. SO BLOOD LA English DT Meeting Abstract C1 INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,DEPT MED,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,DEPT MICROBIOL IMMUNOL,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,DEPT PEDIAT,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,WELLS CTR,INDIANAPOLIS,IN. NIDDK,BIOCHEM & METAB LAB,NIH,BETHESDA,MD. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1698 EP 1698 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301698 ER PT J AU Sabatino, DE Do, BKQ Girard, LJ Orlic, D Bodine, DM AF Sabatino, DE Do, BKQ Girard, LJ Orlic, D Bodine, DM TI Treatment of HL60 cells with PMA and IL-alpha increases the levels of amphotropic and GALV receptor mRNA as well as the efficiency of transduction with amphotropic and GALV retrovirus vectors SO BLOOD LA English DT Meeting Abstract C1 NCHGR,LGT,HEMATOPOIESIS SECT,BETHESDA,MD. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1699 EP 1699 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301699 ER PT J AU Migita, M Stahl, SK Anderson, S Schiffman, R Humphries, RK Karlsson, S AF Migita, M Stahl, SK Anderson, S Schiffman, R Humphries, RK Karlsson, S TI Sorting and optimal transduction conditions for primitive hematopoietic progenitors using the CD24 selectable marker. SO BLOOD LA English DT Meeting Abstract C1 NINCDS,DEV & METAB NEUROL BRANCH,NIH,BETHESDA,MD 20892. NHLBI,HEMATOL BRANCH,NIH,VANCOUVER,BC,CANADA. BRITISH COLUMBIA CANC AGCY,TERRY FOX LAB,VANCOUVER,BC V5Z 1L3,CANADA. GENET THERAPY INC,GAITHERSBURG,MD. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1721 EP 1721 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301721 ER PT J AU Li, F Linton, GF WhitingTheobald, N Malech, HL AF Li, F Linton, GF WhitingTheobald, N Malech, HL TI In situ immunohistochemical detection of small peptide-based marker gene expression among hematopoietic progenitor cells (CFU) following MFG retrovirus transduction SO BLOOD LA English DT Meeting Abstract C1 NIAID,HOST DEF LAB,NIH,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1722 EP 1722 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301722 ER PT J AU Hanazono, Y Dunbar, CE Emmons, RVB AF Hanazono, Y Dunbar, CE Emmons, RVB TI Low titer and high recombination frequency in green fluorescent protein retroviral vector producer cells suggest a selective disadvantage. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,NIH,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1726 EP 1726 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301726 ER PT J AU Maciejewski, JP Kim, S Sato, T Selleri, C Young, NS AF Maciejewski, JP Kim, S Sato, T Selleri, C Young, NS TI LTC-IC in aplastic anemia. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1730 EP 1730 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301730 ER PT J AU Hoshino, T Youssoufian, H Wang, J Devetten, MP Iwata, N Kajigaya, S Liu, JM AF Hoshino, T Youssoufian, H Wang, J Devetten, MP Iwata, N Kajigaya, S Liu, JM TI The molecular chaperone GRP94 binds to a central domain within the group C Fanconi anemia protein. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. NR 0 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1734 EP 1734 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301734 ER PT J AU Chrobak, P Kurasawa, K Bare, CV Henkart, PA Gress, RE AF Chrobak, P Kurasawa, K Bare, CV Henkart, PA Gress, RE TI Suppressibility of cytotoxic responses by veto cells SO BLOOD LA English DT Meeting Abstract C1 NCI,EXPT IMMUNOL BRANCH,NIH,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1740 EP 1740 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301740 ER PT J AU Molldrem, J StetlerStevenson, M Mavroudis, D Young, NS Barrett, AJ AF Molldrem, J StetlerStevenson, M Mavroudis, D Young, NS Barrett, AJ TI Antithymocyte globulin (ATG) abrogates cytopenias in patients with myelodysplastic syndrome. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,BMT UNIT,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1804 EP 1804 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301804 ER PT J AU Barrett, AJ Mavroudis, D Molldrem, J Read, EJ Carter, C Dunbar, C Young, NS AF Barrett, AJ Mavroudis, D Molldrem, J Read, EJ Carter, C Dunbar, C Young, NS TI Optimizing the dose and timing of lymphocyte add-back in T-cell depleted BMT between HLA-identical siblings. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BMT UNIT,BETHESDA,MD 20892. NIH,DEPT TRANSFUS MED,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1830 EP 1830 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301830 ER PT J AU Malech, HL Sekhsaria, S WhitingTheobald, N Linton, GF Vowells, SJ Li, F Miller, JA Holland, SM Leitman, SF Carter, CS Read, EJ Butz, R Wannebo, C Fleisher, TA Deans, RJ Spratt, SK Maack, CA Rokovich, JA Cohen, LK Maples, PB Gallin, JI AF Malech, HL Sekhsaria, S WhitingTheobald, N Linton, GF Vowells, SJ Li, F Miller, JA Holland, SM Leitman, SF Carter, CS Read, EJ Butz, R Wannebo, C Fleisher, TA Deans, RJ Spratt, SK Maack, CA Rokovich, JA Cohen, LK Maples, PB Gallin, JI TI Prolonged detection of oxidase-positive neutrophils in the peripheral blood of five patients following a single cycle of gene therapy for chronic granulomatous disease. SO BLOOD LA English DT Meeting Abstract C1 BAXTER HEALTHCARE CORP,DIV IMMUNOTHERAPY,ROUND LAKE,IL. BAXTER HEALTHCARE CORP,DIV IMMUNOTHERAPY,DUARTE,CA. SOMATIX THERAPY CORP,ALAMEDA,CA. NIAID,HOST DEF LAB,DEPT TRANSFUS MED,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,SERV IMMUNOL,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1934 EP 1934 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301934 ER PT J AU Bunnell, BA Metzger, ME Byrne, ER Clements, JE Morgan, RA Donahue, RE AF Bunnell, BA Metzger, ME Byrne, ER Clements, JE Morgan, RA Donahue, RE TI In vivo protection from simian immunodeficiency virus infection following gene transfer of an antisense Tat/Rev retroviral vector into rhesus CD4+ peripheral blood lymphocytes SO BLOOD LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,DIV COMPARAT MED,BALTIMORE,MD 21205. NIH,CLIN GENE THERAPY BRANCH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NHLBI,HEMATOL BRANCH,NIH,ROCKVILLE,MD 20901. NR 0 TC 0 Z9 0 U1 0 U2 2 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 NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1935 EP 1935 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301935 ER PT J AU Mardiney, M Jackson, SH Spratt, SK Holland, SM Malech, HL AF Mardiney, M Jackson, SH Spratt, SK Holland, SM Malech, HL TI Enhanced host defense after gene transfer in the murine p47(phox)-deficient model of chronic granulomatous disease. SO BLOOD LA English DT Meeting Abstract C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. SOMATIX THERAPY CORP,ALAMEDA,CA. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1938 EP 1938 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301938 ER PT J AU Konijn, AM Vaisman, B MeyronHoltz, EG Leimberg, JM Rouault, TA Fibach, E AF Konijn, AM Vaisman, B MeyronHoltz, EG Leimberg, JM Rouault, TA Fibach, E TI Human erythroid precursors utilize and sense intra- and extra cellular ferritin iron. SO BLOOD LA English DT Meeting Abstract C1 HEBREW UNIV JERUSALEM,FAC MED,DEPT HUMAN NUTR & METAB,IL-91010 JERUSALEM,ISRAEL. HEBREW UNIV JERUSALEM,FAC MED,DEPT HEMATOL,IL-91010 JERUSALEM,ISRAEL. NICHHD,CBMB,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 1943 EP 1943 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98301943 ER PT J AU Eyster, ME Hatzakis, A Goedert, JJ AF Eyster, ME Hatzakis, A Goedert, JJ TI HCV genotypes in multitransfused hemophiliacs. SO BLOOD LA English DT Meeting Abstract C1 PENN STATE UNIV,COLL MED,MULTICTR HEMOPHILIA STUDY GRP,HERSHEY,PA. UNIV ATHENS,SCH MED,GR-11527 ATHENS,GREECE. NATL INST HLTH,BETHESDA,MD. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2093 EP 2093 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302093 ER PT J AU Miller, JL Giattina, MR AF Miller, JL Giattina, MR TI Contact-mediated intercellular transfer of GPI-linked proteins between cultured cells. SO BLOOD LA English DT Meeting Abstract C1 NIDDK,BIOL CHEM LAB,NIH,BETHESDA,MD. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2121 EP 2121 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302121 ER PT J AU Mantel, C Luo, Z Canfield, J Braun, S Deng, C Broxmeyer, HE AF Mantel, C Luo, Z Canfield, J Braun, S Deng, C Broxmeyer, HE TI Involvement of p21(cip-1) and p27(kip-1) in the molecular mechanisms of steel factor induced proliferative synergy in vitro and of p21(cip-1) in the maintenance of stem/progenitor cells in vivo. SO BLOOD LA English DT Meeting Abstract C1 INDIANA UNIV,SCH MED,DEPT MED,INDIANAPOLIS,IN. INDIANA UNIV,SCH MED,DEPT IMMUNOL MICROBIOL,INDIANAPOLIS,IN. INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,INDIANAPOLIS,IN 46202. NIDDK,NIH,BETHESDA,MD. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2144 EP 2144 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302144 ER PT J AU Wellmann, A Thieblemont, C Fest, T Krenacs, L Jaffe, ES Raffeld, M AF Wellmann, A Thieblemont, C Fest, T Krenacs, L Jaffe, ES Raffeld, M TI Detection of NPM-ALK rearrangements using an XL (extra large) PCR assay and an analysis of genomic breakpoint sequences. SO BLOOD LA English DT Meeting Abstract C1 NCI,HEMATOPATHOL SECT,PATHOL LAB,NIH,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 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 NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2196 EP 2196 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302196 ER PT J AU Cao, W BritosBray, M Kelley, CA Speck, NA Liu, PP Friedman, AD AF Cao, W BritosBray, M Kelley, CA Speck, NA Liu, PP Friedman, AD TI CBF beta-SMMHC, encoded by INV(16) in M4EO AML, inhibits hematopoietic cell proliferation. SO BLOOD LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD 21205. NHLBI,BETHESDA,MD 20892. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. DARTMOUTH COLL,SCH MED,HANOVER,NH 03755. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2207 EP 2207 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302207 ER PT J AU Wang, J Wang, M Liu, JM AF Wang, J Wang, M Liu, JM TI Transformation properties of the ETO gene, fusion partner in t(8;21) leukemias. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NIDDK,BIOL CHEM LAB,MOL HEMATOL SECT,BETHESDA,MD. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2211 EP 2211 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302211 ER PT J AU Varterasian, M Eilender, D Mohammad, R Chen, B Hulburd, K Rodriguez, D Pluda, J Valdivieso, M AlKatib, A AF Varterasian, M Eilender, D Mohammad, R Chen, B Hulburd, K Rodriguez, D Pluda, J Valdivieso, M AlKatib, A TI Phase I trial of bryostatin 1 in relapsed lymphoma and CLL. SO BLOOD LA English DT Meeting Abstract C1 WAYNE STATE UNIV,DETROIT,MI. KARMANOS CANC INST,DETROIT,MI. OAKWOOD HEALTHCARE SYST,DEARBORN,MI. NCI,BETHESDA,MD 20892. NR 0 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2269 EP 2269 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302269 ER PT J AU Thompson, P LeBeau, MM Larson, RA Green, ED Shannon, KM AF Thompson, P LeBeau, MM Larson, RA Green, ED Shannon, KM TI Analysis of juvenile chronic myelogenous leukemia (JCML) bone marrows for submicroscopic deletions on 7q. SO BLOOD LA English DT Meeting Abstract C1 UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. UNIV CHICAGO,CHICAGO,IL 60637. NIH,NATL CTR HUMAN GENOME RES,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2324 EP 2324 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302324 ER PT J AU Dermime, S Mavroudis, D Jiang, YZ Hensel, N Molldrem, J Barrett, AJ AF Dermime, S Mavroudis, D Jiang, YZ Hensel, N Molldrem, J Barrett, AJ TI Immune escape from a graft-versus-leukemia effect play a role in the relapse of myelogenous leukemias following allogeneic bone marrow transplantation. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, BMT UNIT, HEMATOL BRANCH, NIH, BETHESDA, MD 20892 USA. RI Dermime, Said/C-6235-2009 OI Dermime, Said/0000-0002-5526-7496 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2430 EP 2430 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302430 ER PT J AU Sloand, E Maciejewski, J Dunn, D Young, N AF Sloand, E Maciejewski, J Dunn, D Young, N TI Transfer of GPI-anchored proteins, CD55 and CD59, to deficient erythrocytes by protein derived from stored red cells, and microvesicles. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2497 EP 2497 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302497 ER PT J AU Bergsagel, PL Chesi, M Lim, R Nardini, E Kuehl, WM AF Bergsagel, PL Chesi, M Lim, R Nardini, E Kuehl, WM TI Dysregulation of fibroblast growth factor receptor 3 (FGFR3) by t(4;14)(p16.3;q32.3) in multiple myeloma. SO BLOOD LA English DT Meeting Abstract C1 CORNELL UNIV,COLL MED,DIV HEMATOL ONCOL,NEW YORK,NY. NCI,NAVAL MED ONCOL BRANCH,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2523 EP 2523 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302523 ER PT J AU Orlic, D Girard, LJ Anderson, SM Dunbar, E Bodine, DM AF Orlic, D Girard, LJ Anderson, SM Dunbar, E Bodine, DM TI Isolation of mouse and human hematopoietic stem cell (HSC) populations with high levels of mRNA encoding retrovirus receptors. SO BLOOD LA English DT Meeting Abstract C1 NCHGR,HEMATOPOLESIS SECT,NIH,BETHESDA,MD. NHLBI,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2566 EP 2566 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302566 ER PT J AU Bunnell, BA LeeLin, SQ Byrne, ER Metzger, ME Agricola, BA Morgan, RA Donahue, RE AF Bunnell, BA LeeLin, SQ Byrne, ER Metzger, ME Agricola, BA Morgan, RA Donahue, RE TI Transduction and transplantation of nonhuman primate CD34+ cells using the gibbon ape leukemia virus packaging cell line, PG13. Restricted expression of the gibbon ape leukemia virus receptor to a subset of CD34+ cells that are small in size and express both CD38 and Thy-1 SO BLOOD LA English DT Meeting Abstract C1 NCHGR,CLIN GENE THERAPY BRANCH,NIH,BETHESDA,MD 20892. NHLBI,HEMATOL BRANCH,NIH,ROCKVILLE,MD 20901. NR 0 TC 1 Z9 1 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 NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2567 EP 2567 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302567 ER PT J AU Sloand, E Sato, T Bruny, J Maciejewski, J Kumar, P Young, N AF Sloand, E Sato, T Bruny, J Maciejewski, J Kumar, P Young, N TI Relationship of interleukin-1 beta converting enzyme activation and Fas triggering of bone marrow cells obtained from HIV infected patients and uninfected controls. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. GEORGETOWN UNIV,WASHINGTON,DC. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2611 EP 2611 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302611 ER PT J AU Viswanatha, DS Chen, IM Liu, PP Slovak, ML Rankin, C Willman, CL AF Viswanatha, DS Chen, IM Liu, PP Slovak, ML Rankin, C Willman, CL TI Characterization end rapid diagnostic utility of a novel antibody detecting the CBF beta/SMMHC fusion protein of inversion(16)/t(16;16) associated acute myeloid leukemia. SO BLOOD LA English DT Meeting Abstract C1 UNIV NEW MEXICO,ALBUQUERQUE,NM 87131. CITY HOPE NATL MED CTR,DUARTE,CA 91010. SWOG,CTR STAT,SEATTLE,WA. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. SWOG,LEUKEMIA BIOL PROGRAM,SAN ANTONIO,TX. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2646 EP 2646 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302646 ER PT J AU TeruyaFeldstein, J Jaffe, ES Burd, PR Kanegane, H Kingma, DW Wilson, WH Longo, DL Tosato, G AF TeruyaFeldstein, J Jaffe, ES Burd, PR Kanegane, H Kingma, DW Wilson, WH Longo, DL Tosato, G TI Expression of interferon-gamma inducible protein (IP-10) and the macrophage interferon-gamma induced gene (MIG) in lymphomatoid granulomatosis and nasal T/NK cell lymphoma with necrosis and vascular damage. SO BLOOD LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. US FDA,BETHESDA,MD 20014. NIA,NIH,BALTIMORE,MD 21224. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2669 EP 2669 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302669 ER PT J AU Fredrickson, T Giese, T Davidson, WF AF Fredrickson, T Giese, T Davidson, WF TI Defective interactions between fas ano fas ligand predispose mice to the development of B cell lymphomas. SO BLOOD LA English DT Meeting Abstract C1 NCI,REGISTRY EXPT CANC,NIH,BETHESDA,MD 20892. NCI,GENET LAB,NIH,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2671 EP 2671 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302671 ER PT J AU Sternas, L Janik, JE Duffey, PL Gocke, C Reynolds, CW Wittes, RE Kwak, LW AF Sternas, L Janik, JE Duffey, PL Gocke, C Reynolds, CW Wittes, RE Kwak, LW TI Early results of a clinical trial of therapeutic vaccination with Ig idiotype antigen for de novo follicular lymphoma. SO BLOOD LA English DT Meeting Abstract C1 NCI,DIV CLIN SCI,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT DIAGNOSIS & CTR,BETHESDA,MD 20892. PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT PATHOL,HERSHEY,PA 17033. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2677 EP 2677 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302677 ER PT J AU Weichold, FF Jiang, YZ Dunn, DE Bloom, M Malkovska, V Barrett, AJ AF Weichold, FF Jiang, YZ Dunn, DE Bloom, M Malkovska, V Barrett, AJ TI Tumors of HLA-DR1 expressing K562 cells in SCID mice are resistant to the antitumor effect of unprimed human lymphocytes SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. WASHINGTON HOSP CTR,WASHINGTON CANC INST,WASHINGTON,DC 20010. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2698 EP 2698 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302698 ER PT J AU Curtis, RE Deeg, HJ Socie, G Horowitz, MM AF Curtis, RE Deeg, HJ Socie, G Horowitz, MM TI Solid cancers after bone marrow transplantation (BMT). SO BLOOD LA English DT Meeting Abstract C1 NCI,CANC FOLLOWING BMT STUDY GRP,BETHESDA,MD 20892. MED COLL WISCONSIN,INT BONE MARROW TRANSPLANT REGISTRY,MILWAUKEE,WI 53226. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2708 EP 2708 PN 1 PG 1 WC Hematology SC Hematology GA VT983 UT WOS:A1996VT98302708 ER PT J AU Broyles, RH Kurien, BT Berg, PE Schechter, AN AF Broyles, RH Kurien, BT Berg, PE Schechter, AN TI DNA looping between the -150 promoter site and upstream regions of the human beta-globin gene. SO BLOOD LA English DT Meeting Abstract C1 UNIV OKLAHOMA,HLTH SCI CTR,OKLAHOMA CITY,OK. OKLAHOMA MED RES FDN,OKLAHOMA CITY,OK 73104. UNIV MARYLAND,BALTIMORE,MD 21201. NIH,BETHESDA,MD 20892. RI Kurien, Biji/C-2392-2008 NR 1 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2819 EP 2819 PN 2 PG 1 WC Hematology SC Hematology GA VT986 UT WOS:A1996VT98600080 ER PT J AU Miller, JS Okazaki, IJ Moss, J AF Miller, JS Okazaki, IJ Moss, J TI Purine metabolites suppress interleukin-2 (IL-2) induced proliferation of normal human natural killer cells (NK). SO BLOOD LA English DT Meeting Abstract C1 UNIV MINNESOTA,DEPT MED,MINNEAPOLIS,MN. NHLBI,NIH,PULM & CRIT CARE MED BRANCH,BETHESDA,MD. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 2900 EP 2900 PN 2 PG 1 WC Hematology SC Hematology GA VT986 UT WOS:A1996VT98600161 ER PT J AU Schwartz, GN Liao, F Szabo, J Hakim, F Gress, RE Farber, JM AF Schwartz, GN Liao, F Szabo, J Hakim, F Gress, RE Farber, JM TI Mig chemokine has suppressive effects on CFU-GM production from CD34+ cells. SO BLOOD LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NIAID,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 3146 EP 3146 PN 2 PG 1 WC Hematology SC Hematology GA VT986 UT WOS:A1996VT98600407 ER PT J AU Kiyama, R Nishikawa, N Hirota, M WadaKiyama, Y Noguchi, CT AF Kiyama, R Nishikawa, N Hirota, M WadaKiyama, Y Noguchi, CT TI Chromatin organization of the human erythropoietin receptor gene locus. SO BLOOD LA English DT Meeting Abstract C1 UNIV TOKYO,INST MOL & CELLULAR BIOSCI,TOKYO,JAPAN. NIPPON MED COLL,DEPT PHYSIOL,TOKYO 113,JAPAN. NIDDK,NIH,CELL BIOL LAB,BETHESDA,MD 20892. NR 1 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 3161 EP 3161 PN 2 PG 1 WC Hematology SC Hematology GA VT986 UT WOS:A1996VT98600422 ER PT J AU Schwartz, GN Rothwell, SW Szabo, JM Halverson, DC Gress, RE AF Schwartz, GN Rothwell, SW Szabo, JM Halverson, DC Gress, RE TI Cytokine pretreated stromal cell layers from normal donor marrow suppressed the production of committed progenitors. SO BLOOD LA English DT Meeting Abstract C1 NATL CANC INST,BETHESDA,MD. WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,WASHINGTON,DC 20307. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 3244 EP 3244 PN 2 PG 1 WC Hematology SC Hematology GA VT986 UT WOS:A1996VT98600505 ER PT J AU Mantel, C Luo, ZM Canfield, J Braun, S Deng, CX Broxmeyer, HE AF Mantel, C Luo, ZM Canfield, J Braun, S Deng, CX Broxmeyer, HE TI Involvement of p21(cip-1) and p27(kip-1) in the molecular mechanisms of steel factor-induced proliferative synergy in vitro and of p21(cip-1) in the maintenance of stem/progenitor cells in vivo SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; RETINOBLASTOMA GENE-PRODUCT; DEPENDENT KINASE INHIBITOR; C-KIT LIGAND; CYCLIN KINASES; LINE; INDUCTION; P21; PHOSPHORYLATION AB Steel factor (SLF) is a hematopoietic cytokine that synergizes with other growth factors to induce a greatly enhanced proliferative state of hematopoietic progenitor cells and factor-dependent cell lines, Even though the in vivo importance of SLF in the maintenance and responsiveness of stem and progenitor cells is well documented, the molecular mechanisms involved in its synergistic effects are mainly unknown. Some factor-dependent myeloid cell lines respond to the synergistic proliferative effects of SLF plus other cytokines in a manner similar to that of normal myeloid progenitor cells from bone marrow and cord blood, We show here that SLF can synergize with granulocyte-macrophage colony-stimulating factor (GM-CSF) to induce an enhanced phosphorylation of the retinoblastoma gene product and a synergistic increase in the total intracellular protein level of the cyclin-dependent kinase inhibitor, p21(cip-1), which is correlated with a simultaneous decrease in p27(kip-1) in the human factor-dependent myeloid cell line, M07e. Moreover, these cytokines synergize to increase p21(cip-1) binding and decrease p27(kip-1) binding to cyclin-dependent kinase-2 (cdk2), an enzyme required for normal cell cycle progression; these inverse events correlated with increased cdk2 kinase activity, it is also shown that exogenous purified p21(cip-1) can displace p27(kip-1) already bound to cdk2 in vitro, These data implicate increased p21(cip-1) and decreased p27(kip-1) intracellular concentrations and their stoichiometric interplay in the enhanced proliferative status of cells stimulated by the combination of SLF and GM-CSF, In support of these findings, it is shown that hematopoietic progenitor cells from mice lacking p21(cip-1) are defective in SLF synergistic proliferative response in vitro, Moreover, the cycling status of marrow and spleen progenitors and absolute numbers of marrow progenitors were significantly decreased in the p21(cip-1) -/-, compared with the +/+ mice, We conclude that the cdk threshold regulators p21(cip-1) and p27(kip-1) play a critical role in the normal mitogenic response of M07e cells and murine myeloid progenitor cells to these cytokines and particularly in the SLF synergistic proliferative response that is important to the normal maintenance of the stem/progenitor cell compartment. (C) 1996 by The American Society of Hematology. C1 INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,DEPT MED HEMATOL ONCOL,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,INDIANAPOLIS,IN 46202. NIDDK,BIOCHEM & METAB LAB,NIH,BETHESDA,MD. RI deng, chuxia/N-6713-2016 FU NHLBI NIH HHS [R01 HL56416]; PHS HHS [R01 54037] NR 41 TC 94 Z9 94 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 NOV 15 PY 1996 VL 88 IS 10 BP 3710 EP 3719 PG 10 WC Hematology SC Hematology GA VU984 UT WOS:A1996VU98400005 PM 8916935 ER PT J AU Turturro, F Lay, T Wroblewski, J Seth, P Meeker, T AF Turturro, F Lay, T Wroblewski, J Seth, P Meeker, T TI Adenoviral vectors efficiently target cell lines derived from selected lymphocytic malignancies. SO BLOOD LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. UNIV KENTUCKY,DEPT INTERNAL MED,DIV HEMATOL ONCOL,LEXINGTON,KY. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 3905 EP 3905 PN 2 PG 1 WC Hematology SC Hematology GA VT986 UT WOS:A1996VT98601166 ER PT J AU Wiener, SM Hoyt, RF DeLeonardis, J Clevenger, RR Kotin, RM Safer, B AF Wiener, SM Hoyt, RF DeLeonardis, J Clevenger, RR Kotin, RM Safer, B TI Tissue tropism of adeno-associated virus (human type 2) in mice. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,MOL HEMATOL BRANCH,NATL INST HLTH,BETHESDA,MD 20892. NHLBI,LAB ANIM MED & SURG,NATL INST HLTH,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 3906 EP 3906 PN 2 PG 1 WC Hematology SC Hematology GA VT986 UT WOS:A1996VT98601167 ER PT J AU Cooke, KS Agricola, BA Kirby, MR Wersto, RP Hege, KM Finer, MF Roberts, MR Donahue, RE AF Cooke, KS Agricola, BA Kirby, MR Wersto, RP Hege, KM Finer, MF Roberts, MR Donahue, RE TI A comparison of retroviral transduction protocols for gene transfer into rhesus CD34(+) bone marrow cells. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,ROCKVILLE,MD. CELL GENESYS INC,FOSTER CITY,CA. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 3916 EP 3916 PN 2 PG 1 WC Hematology SC Hematology GA VT986 UT WOS:A1996VT98601181 ER PT J AU Ding, I Huang, HD Sabet, H Zou, ZO Zhang, LR Kern, FG Okunieff, P AF Ding, I Huang, HD Sabet, H Zou, ZO Zhang, LR Kern, FG Okunieff, P TI Expression of maspin by human breast tumor cells inhibits primary tumor cell growth and lung metastasis in an athymic mouse model. SO BLOOD LA English DT Meeting Abstract C1 NCI,RADIAT ONCOL BRANCH,NIH,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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 3917 EP 3917 PN 2 PG 1 WC Hematology SC Hematology GA VT986 UT WOS:A1996VT98601182 ER PT J AU Robinet, E Certoux, JM Maples, PB Hardwick, A Cahn, JY Reynolds, CW Jacob, W Herve, P Tiberghien, P AF Robinet, E Certoux, JM Maples, PB Hardwick, A Cahn, JY Reynolds, CW Jacob, W Herve, P Tiberghien, P TI Retroviral-mediated gene transfer in human T lymphocytes for clinical use. Assessment of a closed culture system. SO BLOOD LA English DT Meeting Abstract C1 BAXTER HEALTHCARE CORP,ROUND LAKE,IL 60073. ETS FRANCHE COMTE,BESANCON,FRANCE. CHU MINJOZ,BESANCON,FRANCE. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD. GENET THERAPY INC,GAITHERSBURG,MD. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1996 VL 88 IS 10 SU 1 BP 3928 EP 3928 PN 2 PG 1 WC Hematology SC Hematology GA VT986 UT WOS:A1996VT98601189 ER PT J AU Reifenberger, G Ichimura, K Reifenberger, J Elkahloun, AG Meltzer, PS Collins, VP AF Reifenberger, G Ichimura, K Reifenberger, J Elkahloun, AG Meltzer, PS Collins, VP TI Refined mapping of 12q13-q15 amplicons in human malignant gliomas suggests CDK4/SAS and MDM2 as independent amplification targets SO CANCER RESEARCH LA English DT Article ID SOFT-TISSUE TUMORS; HUMAN SARCOMAS; GENE AMPLIFICATION; CELL-LINES; REGION; PROTEIN; SAS; OVEREXPRESSION; CHROMOSOME-12; IDENTIFICATION AB We have reported previously that about 15% of anaplastic astrocytomas and glioblastomas show amplification and overexpression of one or more genes from chromosomal segment 12q13-q15 (G. Reifenberger et al., Cancer Res., 54, 4299-4303, 1994). The genes most frequently amplified and overexpressed were CDK4 (with coamplification of SAS) and MDM2. Because individual malignant gliomas showed CDK4/SAS amplification but no MDM2 amplification and vice versa, the possibility remained of a common amplification target gene located between CDK4 and MDM2. We have addressed this question by performing a detailed amplicon mapping of a series of 24 primary malignant gliomas and two glioblastoma cell lines with 12q13-q15 amplification. All tumors and cell lines were analyzed at eight gene loci and six anonymous loci from 12q13-q15, including seven loci located between CDK4 and MDM2. These studies revealed two centers of amplification, one at CDK4/SAS and the other at MDM2. A number of loci located close to either MDM2 or CDK4/SAS, including the genes GADD153, GLI, RAP1B, A2MR, and IFNG, were found to be coamplified in some tumors but not overexpressed consistently. All amplicons were discontinuous between CDK4/SAS and MDM2. Our results thus exclude a common amplification target between CDK4/SAS and MDM2 and provide additional evidence that these genes represent two independent targets of selection. C1 LUDWIG INST CANC RES,S-10401 STOCKHOLM,SWEDEN. KAROLINSKA HOSP,KING GUSTAF V RES INST,DIV TUMOR PATHOL,INST ONCOL & PATHOL,S-17176 STOCKHOLM,SWEDEN. UNIV DUSSELDORF,DEPT NEUROPATHOL,D-40225 DUSSELDORF,GERMANY. UNIV DUSSELDORF,CTR BIOL & MED RES,D-40225 DUSSELDORF,GERMANY. UNIV DUSSELDORF,DEPT DERMATOL,D-40225 DUSSELDORF,GERMANY. NIH,CANC GENET LAB,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NR 40 TC 150 Z9 153 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 NOV 15 PY 1996 VL 56 IS 22 BP 5141 EP 5145 PG 5 WC Oncology SC Oncology GA VT338 UT WOS:A1996VT33800008 PM 8912848 ER PT J AU Hsing, AY Kadomatsu, K Bonham, MJ Danielpour, D AF Hsing, AY Kadomatsu, K Bonham, MJ Danielpour, D TI Regulation of apoptosis induced by transforming growth factor-beta 1 in nontumorigenic and tumorigenic rat prostatic epithelial cell lines SO CANCER RESEARCH LA English DT Article ID FACTOR-BETA; FACTOR-I; DEATH; PROLIFERATION AB Transforming growth factor-beta 1 (TGF-beta 1), which is induced in the prostate following castration, has been speculated to mediate apoptosis of epithelial cells during prostatic involution. Here, we report the first evidence of a direct effect of TGF-beta on induction of apoptosis in prostatic epithelial cells in vitro, using NRP-152 nontumorigenic and NRP-154 tumorigenic rat prostatic epithelial cell lines. TGF-beta 1 induces apoptosis of both cell lines within 24 h, as shown by a decrease in cell viability, in situ DNA nick-end labeling, and internucleosomal DNA fragmentation. Moreover, the ability of TGF-beta to induce apoptosis of NRP-152 is strictly dependent on culture conditions, because dexamethasone enhances while insulin and insulin-like growth factor-I specifically block apoptosis induced by TGP-beta. We suggest that TGF-beta s are direct physiological regulators of apoptosis of prostatic epithelial cells. C1 NCI,CHEMOPREVENT LAB,NIH,BETHESDA,MD 20892. RI Kadomatsu, Kenji/G-8083-2012 NR 22 TC 115 Z9 122 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 NOV 15 PY 1996 VL 56 IS 22 BP 5146 EP 5149 PG 4 WC Oncology SC Oncology GA VT338 UT WOS:A1996VT33800009 PM 8912849 ER PT J AU Koo, HM Monks, A Mikheev, A Rubinstein, LV GrayGoodrich, M McWilliams, MJ Alvord, WG Oie, HK Gazdar, AF Paull, KD Zarbl, H VandeWoude, GF AF Koo, HM Monks, A Mikheev, A Rubinstein, LV GrayGoodrich, M McWilliams, MJ Alvord, WG Oie, HK Gazdar, AF Paull, KD Zarbl, H VandeWoude, GF TI Enhanced sensitivity to 1-beta-D-arabinofuranosylcytosine and topoisomerase II inhibitors in tumor cell lines harboring activated ras oncogenes SO CANCER RESEARCH LA English DT Article ID NATIONAL-CANCER-INSTITUTE; DIFFERENTIAL CYTOTOXICITY DATA; ANTICANCER DRUG SCREEN; GENOMIC INSTABILITY; MISMATCH REPAIR; GENE-MUTATIONS; CYCLE CONTROL; LUNG-CANCER; PHASE-II; GEMCITABINE AB We used human tumor cell lines from the National Cancer Institute's In Vitro Antineoplastic Drug Screen to assess whether sensitivity to any of the similar to 45,000 compounds tested previously correlated with the presence of a ras oncogene. Among these cell lines, the mutations in Ki-ras2 clustered in non-small cell lung and colon carcinoma subpanels, and five of the six leukemia lines contained mutations in either N-ras or Ki-ras2. These analyses revealed a striking correlation with 1-beta-D-arabinofuranosylcytosine (Ara-C) and 2,2'-O-cyclocytidine sensitivity in the cell lines harboring ras mutations compared to the tumor lines with wild-type ras alleles. Strong correlations were also found with topoisomerase (topo) II inhibitors, especially 3'-hydroxydaunorubicin and an olivacine derivative. These differential sensitivities persisted in an additional 22 non-small cell lung carcinoma lines (ras mutations, n = 12 and wild-type ras, n = 10). Thus, the association with Ara-C sensitivity was greatest while topo II inhibitors showed a lower, but significant, correlation. These results suggest that the ras oncogene may play a determinant role in rendering tumor cells sensitive to deoxycytidine analogues and topo II inhibitors. C1 NCI,ABL BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NCI,SCI APPLICAT INT CORP,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. MIT,CAMBRIDGE,MA 02139. NCI,DIV CANC TREATMENT,NIH,BETHESDA,MD 20892. NCI,DATA MANAGEMENT SERV INC,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. UNIV TEXAS,SW MED CTR,DEPT PATHOL,DALLAS,TX 75235. UNIV TEXAS,SW MED CTR,SIMMONS CANC CTR,DALLAS,TX 75235. NR 54 TC 78 Z9 80 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 NOV 15 PY 1996 VL 56 IS 22 BP 5211 EP 5216 PG 6 WC Oncology SC Oncology GA VT338 UT WOS:A1996VT33800019 PM 8912859 ER PT J AU Gustafson, CE Wilson, PJ Lukeis, R Baker, E Woollatt, E Annab, L Hawke, L Barrett, JC ChenevixTrench, G AF Gustafson, CE Wilson, PJ Lukeis, R Baker, E Woollatt, E Annab, L Hawke, L Barrett, JC ChenevixTrench, G TI Functional evidence for a colorectal cancer tumor suppressor gene at chromosome 8p22-23 by monochromosome transfer SO CANCER RESEARCH LA English DT Article ID HUMAN PROSTATE-CANCER; FREQUENT LOSS; CELL-LINES; HEPATOCELLULAR-CARCINOMA; SQUAMOUS-CELL; LUNG-CANCER; ALLELE LOSS; HETEROZYGOSITY; DELETION; LOCI AB Chromosome 8p is considered, from loss of heterozygosity analysis, to be a strong candidate for the location of a tumor suppressor gene inactivated in colorectal cancer. We have found a 53% (27 of 51) rate of allelic loss at the LPL locus on 8p22, with the smallest region of overlap of deletions including the region D8S258 to D8S277. Using microcell-mediated monochromosome 8 transfer into three colorectal cancer cell lines, SW480, SW620 and HT29, we have demonstrated a reduction of tumorigenicity in SW620 hybrids. Partial deletions of chromosome 8 in some SW620/8 hybrids further delineate the critical region(s) to 8p22-23. Hybrids of the colorectal cancer cell lines SW480 and HT29 containing chromosome 8 did not show suppression of tumorigenesis, but the H29/8 hybrid showed total suppression of soft agar clonicity. This indicates an alternate pathway of mutational progression in these three lines, despite the fact that SW480 was derived from the same patient as SW620. C1 QUEENSLAND INST MED RES,BANCROFT CTR,BRISBANE,QLD 4029,AUSTRALIA. ROYAL PRINCE ALFRED HOSP,KANEMATSU LABS,SYDNEY,NSW 2000,AUSTRALIA. WOMENS & CHILDRENS HOSP,DEPT CYTOGENET & MOL GENET,ADELAIDE,SA 5006,AUSTRALIA. NIEHS,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. NR 47 TC 61 Z9 61 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 NOV 15 PY 1996 VL 56 IS 22 BP 5238 EP 5245 PG 8 WC Oncology SC Oncology GA VT338 UT WOS:A1996VT33800023 PM 8912863 ER PT J AU Lubensky, IA Debelenko, LV Zhuang, ZP EmmertBuck, MR Dong, QH Chandrasekharappa, S Guru, SC Manickam, P Olufemi, SE Marx, SJ Spiegel, AM Collins, FS Liotta, LA AF Lubensky, IA Debelenko, LV Zhuang, ZP EmmertBuck, MR Dong, QH Chandrasekharappa, S Guru, SC Manickam, P Olufemi, SE Marx, SJ Spiegel, AM Collins, FS Liotta, LA TI Allelic deletions on chromosome 11q13 in multiple tumors from individual MEN1 patients SO CANCER RESEARCH LA English DT Article ID ENDOCRINE NEOPLASIA TYPE-1; PARATHYROID TUMORS; MULTICELLULAR ORIGIN; SMALL REGION; GENE; ADENOMAS; MONOCLONALITY; LOCALIZATION; CLONALITY; MARKERS AB Familial multiple endocrine neoplasia type 1 is an autosomal dominant hereditary disorder characterized by multiple parathyroid, pancreatic, duodenal, and pituitary tumors. The parathyroid tumors may arise as diffuse areas of hyperplasia, whereas the pancreatic and duodenal tumors usually form as discrete nodules. Except for a single report, tumor loss of heterozygosity (LOH) mapping of the putative MEN1 suppressor gene on chromosome 11q13 in the past has been restricted by analysis of a single tumor from individual patients and somatic cellular contamination. For this reason, it has not been possible to analyze the clonality of the emerging MEN1 neoplasms. Furthermore, it has been previously unknown whether the LOH pattern varies between individual MEN1 tumors in a given patient or among tumors of different histological origins within unrelated patients. To address these previous limitations, the present study introduces a refinement in microdissection in which endothelial cells are stained and selectively excluded. Tissue microdissection was applied to study LOH patterns on chromosome 11q13 using 8 polymorphic DNA markers in 44 different MEN1 tumors from parathyroid, pancreas, and duodenum in nine unrelated patients. In addition, X-chromosome inactivation clonal analysis was applied to 16 individual microdissected regions from seven parathyroid glands in three female patients. The LOH rates of parathyroid lesions (100%) and endocrine tumors of the pancreas (83%) were strikingly different from the LOH rate of gastrinomas (21%), suggesting that the mechanism that drives LOH may be influenced by the tissue context. Moreover, combined LOH and X-chromosome inactivation scoring of the same microdissected region revealed that parathyroid MEN1 neoplasms can consist of more than one clone. In this study, the centromeric boundary of the putative MEN1 gene was PYGM. Analysis of differential LOH patterns in multiple microdissected tumors in the same patient constitutes a novel approach to suppressor gene mapping. C1 NIDDKD,METAB DIS BRANCH,NIH,BETHESDA,MD 20892. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP Lubensky, IA (reprint author), NCI,PATHOL LAB,NIH,BLDG 10,ROOM 2N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 30 TC 117 Z9 120 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 NOV 15 PY 1996 VL 56 IS 22 BP 5272 EP 5278 PG 7 WC Oncology SC Oncology GA VT338 UT WOS:A1996VT33800028 PM 8912868 ER PT J AU Guadagni, F Roselli, M Cosimelli, M Spila, A Cavaliere, F Tedesco, M Arcuri, R Abbolito, MR Casale, V Pericoli, MN Vecchione, A Casciani, CU Greiner, JW Schlom, J AF Guadagni, F Roselli, M Cosimelli, M Spila, A Cavaliere, F Tedesco, M Arcuri, R Abbolito, MR Casale, V Pericoli, MN Vecchione, A Casciani, CU Greiner, JW Schlom, J TI Correlation between tumor-associated glycoprotein 72 mucin levels in tumor and serum of colorectal patients as measured by the quantitative CA 72-4 immunoassay SO CANCER RESEARCH LA English DT Article ID MONOCLONAL-ANTIBODY B72.3; SIALYL-TN ANTIGEN; CANCER-PATIENTS; COLON CANCER; RADIOIMMUNOGUIDED SURGERY; CARCINOEMBRYONIC ANTIGEN; CARCINOMA PATIENTS; GASTRIC-CANCER; TAG-72; PROGNOSIS AB Colorectal tissue biopsies were obtained from 110 patients diagnosed with primary colorectal carcinoma (tumor and normal colonic mucosa samples), 20 patients diagnosed with benign colorectal disease, and 31 healthy donors. The level of expression of tumor-associated glycoprotein 72 (TAG-72) was quantitatively measured in each sample using a double-determinant RIA with monoclonal antibodies B72.3 and CC49 and detecting the sialyl-Tn epitope; this assay was termed CA 72-4. Statistical analysis revealed a significant (approximately 10-fold) increase of TAG-72 expression in the colon tumor biopsies when compared with the expression in normal colonic mucosa from the same patients. A regression analysis revealed a significant correlation (r = 0.459; P < 0.001) between TAG-72 levels measured in biopsies from the tumor lesions and those found in the corresponding normal colonic mucosa. Furthermore, regression analysis showed a significant positive correlation between TAG-72 levels in the tumors and sera of the same patients (r = 0.491; P < 0.001). TAG-72 levels in normal colonic mucosa from healthy donors and patients diagnosed with colorectal cancer mere compared. TAG-72 expression was 5-fold higher in the normal mucosa from the colorectal carcinoma patients. No relationship between TAG-72 tumor tissue content and stage of disease was found. Moreover, the correlation between TAG-72 distribution and degree of tumor differentiation observed (P < 0.05) was not any more evident when mucinous carcinomas were excluded. Finally, the results provide further evidence that TAG-72 may be considered an important early marker for colorectal cancer and/or other dysplastic colonic diseases. The statistical correlation between TAG-72 levels in tumors and circulating TAG-72 indicates that patients with elevated levels of serum TAG-72, as measured by the CA 72-4 assay, would be most suited for diagnostic and/or therapeutic intervention with the anti-TAG-72 monoclonal antibodies B72.3 or CC49 or vaccine trials using the sialyl-Tn epitope. C1 NCI,TUMOR IMMUNOL & BIOL LAB,NIH,BETHESDA,MD 20892. UNIV ROMA TOR VERGATA,SCH MED,DEPT SURG,I-00100 ROME,ITALY. REGINA ELENA INST CANC RES,CLIN PATHOL LAB,I-00161 ROME,ITALY. REGINA ELENA INST CANC RES,DEPT SURG,I-00161 ROME,ITALY. REGINA ELENA INST CANC RES,DEPT DIGEST ENDOSCOPY,I-00161 ROME,ITALY. REGINA ELENA INST CANC RES,DEPT CYTOPATHOL,I-00161 ROME,ITALY. UNIV ROMA LA SAPIENZA,DEPT EXPT MED & PATHOL,I-00161 ROME,ITALY. RI Guadagni, Fiorella/J-4432-2013; Cavaliere, Francesco/J-7635-2016 OI Guadagni, Fiorella/0000-0003-3652-0457; Cavaliere, Francesco/0000-0001-6501-8648 NR 35 TC 17 Z9 17 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 NOV 15 PY 1996 VL 56 IS 22 BP 5293 EP 5298 PG 6 WC Oncology SC Oncology GA VT338 UT WOS:A1996VT33800031 PM 8912871 ER PT J AU Fletcher, CF Lutz, CM OSullivan, TN Shaughnessy, JD Hawkes, R Frankel, WN Copeland, NG Jenkins, NA AF Fletcher, CF Lutz, CM OSullivan, TN Shaughnessy, JD Hawkes, R Frankel, WN Copeland, NG Jenkins, NA TI Absence epilepsy in tottering mutant mice is associated with calcium channel defects SO CELL LA English DT Article ID TYROSINE-HYDROXYLASE GENE; PROGRAMMED CELL-DEATH; CA2+ CHANNELS; INTRACELLULAR CALCIUM; SELECTIVE INCREASE; CENTRAL NEURONS; PURKINJE-CELLS; SPIKE-WAVE; MOUSE; EXPRESSION AB Mutations at the mouse tottering (tg) locus cause a delayed-onset, recessive neurological disorder resulting in ataxia, motor seizures, and behavioral absence seizures resembling petit mal epilepsy in humans. A more severe allele, leaner (tg(la)), also shows a slow, selective degeneration of cerebellar neurons. By positional cloning, we have identified an alpha(1A) voltage-sensitive calcium channel gene that is mutated in tg and tg(la) mice. The alpha(1A) gene is widely expressed in the central nervous system with prominent, uniform expression in the cerebellum. alpha(1A) expression does not mirror the localized pattern of cerebellar degeneration observed in tg(la) mice, providing evidence for regional differences in biological function of alpha(1A) channels. These studies define the first mutations in a mammalian central nervous system-specific voltage-sensitive calcium channel and identify the first gene involved in absence epilepsy. C1 JACKSON LAB,BAR HARBOR,ME 04609. UNIV CALGARY,FAC MED,DEPT ANAT,CALGARY,AB T2N 4N1,CANADA. UNIV CALGARY,FAC MED,NEUROSCI RES GRP,CALGARY,AB T2N 4N1,CANADA. RP Fletcher, CF (reprint author), NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702, USA. RI Hawkes, Richard/F-7971-2011 NR 68 TC 549 Z9 557 U1 7 U2 22 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD NOV 15 PY 1996 VL 87 IS 4 BP 607 EP 617 DI 10.1016/S0092-8674(00)81381-1 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VU035 UT WOS:A1996VU03500004 PM 8929530 ER PT J AU Castilla, LH Wijmenga, C Wang, Q Stacy, T Speck, NA Eckhaus, M MarinPadilla, M Collins, FS WynshawBoris, A Liu, PP AF Castilla, LH Wijmenga, C Wang, Q Stacy, T Speck, NA Eckhaus, M MarinPadilla, M Collins, FS WynshawBoris, A Liu, PP TI Failure of embryonic hematopoiesis and lethal hemorrhages in mouse embryos heterozygous for a knocked-in leukemia gene CBFB-MYH11 SO CELL LA English DT Article ID ACUTE MYELOID-LEUKEMIA; CORE-BINDING-FACTOR; MYOSIN HEAVY-CHAIN; ACUTE LYMPHOBLASTIC-LEUKEMIA; RECEPTOR-DELTA-ENHANCER; TRANSCRIPTION FACTOR; ERYTHROID DEVELOPMENT; MICE LACKING; AML1 GENE; C-MYB AB The fusion oncogene CBFB-MYH11 is generated by a chromosome 16 inversion in human acute myeloid leukemia subtype M4Eo. Mouse embryonic stem (ES) cells heterozygous for this oncogene were generated by inserting part of the human MYH11 cDNA into the mouse Cbfb gene through homologous recombination (knock-in). Chimeric mice were leukemia free, but the ES cells with the knocked-in Cbfb-MYH11 gene did not contribute to their hematopoietic tissues. Mouse embryos heterozygous for Cbfb-MYH11 lacked definitive hematopoiesis and developed multiple fatal hemorrhages around embryonic day 12.5. This phenotype is very similar to that resulting from homozygous deletions of either Cbfb or Cbfa2 (AML1), consistent with a dominant negative function of the Cbfb-MYH11 fusion oncogene. An impairment of primitive hematopoiesis was also observed, however, suggesting a possible additional function of Cbfb-MYH11. C1 NIH,NATL CTR HUMAN GENOME RES,LAB GENET DIS RES,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BETHESDA,MD 20892. DARTMOUTH COLL SCH MED,DEPT BIOCHEM,HANOVER,NH 03755. DARTMOUTH COLL SCH MED,DEPT PATHOL,HANOVER,NH 03755. RP Castilla, LH (reprint author), NIH,NATL CTR HUMAN GENOME RES,LAB GENE TRANSFER,BETHESDA,MD 20892, USA. RI Liu, Paul/A-7976-2012; Wijmenga, Cisca/D-2173-2009; OI Liu, Paul/0000-0002-6779-025X; Wijmenga, Cisca/0000-0002-5635-1614 FU NCI NIH HHS [CA58343] NR 41 TC 213 Z9 219 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD NOV 15 PY 1996 VL 87 IS 4 BP 687 EP 696 DI 10.1016/S0092-8674(00)81388-4 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VU035 UT WOS:A1996VU03500011 PM 8929537 ER PT J AU Wang, Q Stacy, T Miller, JD Lewis, AF Gu, TL Huang, XM Bushweller, JH Bories, JC Alt, FW Ryan, G Liu, PP WynshawBoris, A Binder, M MarinPadilla, M Sharpe, AH Speck, NA AF Wang, Q Stacy, T Miller, JD Lewis, AF Gu, TL Huang, XM Bushweller, JH Bories, JC Alt, FW Ryan, G Liu, PP WynshawBoris, A Binder, M MarinPadilla, M Sharpe, AH Speck, NA TI The CBF beta subunit is essential for CBF alpha 2 (AML1) function in vivo SO CELL LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; MOUSE EMBRYO; RUNT DOMAIN; TRANSCRIPTION FACTORS; TARGETED MUTATION; CEREBRAL-CORTEX; CHIMERIC MICE; PROTEIN RBTN2; YOLK-SAC AB The CBF beta subunit is the non-DNA-binding subunit of the heterodimeric core-binding factor (CBF). CBF beta associates with DNA-binding CBF alpha subunits and increases their affinity for DNA. Genes encoding the CBF beta subunit (CBFB) and one of the CBF alpha subunits (CBFA2, otherwise known as AML1) are the most frequent targets of chromosomal translocations in acute leukemias in humans. We and others previously demonstrated that homozygous disruption of the mouse Cbfa2 (AML1) gene results in embryonic lethality at midgestation due to hemorrhaging in the central nervous system and blocks fetal liver hematopoiesis. Here we demonstrate that homozygous mutation of the Cbfb gene results in the same phenotype. Our results demonstrate that the CBF beta subunit is required for CBF alpha 2 function in vivo. C1 DARTMOUTH COLL,DEPT CHEM,HANOVER,NH 03755. CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02215. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. DARTMOUTH COLL SCH MED,DEPT ANAT,HANOVER,NH 03755. DARTMOUTH COLL SCH MED,DEPT PATHOL,HANOVER,NH 03755. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. RP Wang, Q (reprint author), DARTMOUTH COLL SCH MED,DEPT BIOCHEM,HANOVER,NH 03755, USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X FU NCI NIH HHS [CA58343]; NIAID NIH HHS [AI39536-01]; NINDS NIH HHS [NS22897] NR 46 TC 467 Z9 471 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD NOV 15 PY 1996 VL 87 IS 4 BP 697 EP 708 DI 10.1016/S0092-8674(00)81389-6 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VU035 UT WOS:A1996VU03500012 PM 8929538 ER PT J AU Stamler, J Caggiula, A Grandits, GA Kjelsberg, M Cutler, JA AF Stamler, J Caggiula, A Grandits, GA Kjelsberg, M Cutler, JA TI Relationship to blood pressure of combinations of dietary macronutrients - Findings of the multiple risk factor intervention trial (MRFIT) SO CIRCULATION LA English DT Article DE blood pressure; diet; prevention; proteins; lipids ID URINARY ELECTROLYTE EXCRETION; SERUM-CHOLESTEROL; VEGETARIAN DIETS; SALT REDUCTION; POPULATIONS; INTERSALT; HEALTH; HYPERTENSION; MORTALITY; PROTEIN AB Background Elevated blood pressure remains a widespread major impediment to health. Obesity and specific dietary factors such as high salt and alcohol intake and low potassium intake adversely affect blood pressure. It is a reasonable hypothesis that additional dietary constituents, particularly macronutrients, may also influence blood pressure. Methods and Results Participants were 11 342 middle-aged men from the Multiple Risk Factor Intervention Trial (MRFIT). Data from repeat 24-hour dietary recalls (four to five per person) and blood pressure measurements at six annual visits were used to assess relationships, singly and in combination, of dietary macronutrients to blood pressure, adjusted for multiple possible confounders (demographic, dietary, and biomedical). Multiple linear regression was used to assess diet-blood pressure relations in two MRFIT treatment groups (special intervention and usual care), with adjustment for confounders, pooling of coefficients from the two groups (weighted by inverse of variance), and correction of coefficients for regression-dilution bias. In multivariate regression models, dietary cholesterol (milligrams per 1000 kilocalories), saturated fatty acids (percent of kilocalories), and starch (percent of kilocalories) were positively related to blood pressure; protein and the ratio of dietary polyunsaturated to saturated fatty acids were inversely related to blood pressure. These macronutrient-blood pressure findings were obtained in analyses that controlled for body mass, dietary sodium and ratio of sodium to potassium, and alcohol intake, each positively related to blood pressure, and intake of potassium and caffeine, both inversely related to blood pressure. Conclusions These data support the concept that multiple dietary factors influence blood pressure; hence, broad improvements in nutrition can be important in preventing and controlling high-normal and high blood pressure. C1 NORTHWESTERN UNIV, SCH MED, DEPT PREVENT MED, CHICAGO, IL USA. UNIV PITTSBURGH, GRAD SCH PUBL HLTH, DEPT EPIDEMIOL, PITTSBURGH, PA USA. UNIV MINNESOTA, SCH PUBL HLTH, DIV BIOSTAT, MINNEAPOLIS, MN 55414 USA. NHLBI, DIV EPIDEMIOL & CLIN APPLICAT, BETHESDA, MD 20892 USA. NR 53 TC 123 Z9 128 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 15 PY 1996 VL 94 IS 10 BP 2417 EP 2423 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VT114 UT WOS:A1996VT11400013 PM 8921782 ER PT J AU Broeks, A Gerrard, B Allikmets, R Dean, M Plasterk, RHA AF Broeks, A Gerrard, B Allikmets, R Dean, M Plasterk, RHA TI Homologues of the human multidrug resistance genes MRP and MDR contribute to heavy metal resistance in the soil nematode Caenorhabditis elegans SO EMBO JOURNAL LA English DT Article DE arsenite; cadmium; C-elegans; multidrug resistance-associated protein; P-glycoprotein ID P-GLYCOPROTEIN GENE; CHLORIDE CHANNELS; DRUG-RESISTANCE; PROTEIN MRP; LEISHMANIA-TARENTOLAE; COMPLEMENTARY-DNA; HUMAN-TISSUES; EXPORT PUMP; CELL-LINES; C-ELEGANS AB Acquired resistance of mammalian cells to multiple chemotherapeutic drugs can result from enhanced expression of the multidrug resistance-associated protein (MRP), which belongs to the ABC transporter superfamily, ABC transporters play a role in the protection of organisms against exogenous toxins by cellular detoxification processes, We have identified four MRP homologues in the soil nematode Caenorhabditis elegans, and we have studied one member, mrp-1, in detail, Using an mrp::lacZ gene fusion, mrp-1 expression was found in cells of the pharynx, the pharynx-intestinal valve and the anterior intestinal cells, the rectum-intestinal valve and the epithelial cells of the vulva, Targeted inactivation of mrp-1 resulted in increased sensitivity to the heavy metal ions cadmium and arsenite, to which wild-type worms are highly tolerant. The most pronounced effect of the mrp-1 mutation is on the ability of animals to recover from temporary exposure to high concentrations of heavy metals, Nematodes were found to be hypersensitive to heavy metals when both the MRP homologue, mrp-1, and a member of the P-glycoprotein (Pgp) gene family, pgp-1, were deleted, We conclude that nematodes have multiple proteins, homologues of mammalian proteins involved in the cellular resistance to chemotherapeutic drugs, that protect them against heavy metals. C1 NETHERLANDS CANC INST,DIV MOL BIOL,NL-1066 CX AMSTERDAM,NETHERLANDS. NCI,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU NCRR NIH HHS [RR10082-02] NR 80 TC 170 Z9 182 U1 0 U2 11 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 NOV 15 PY 1996 VL 15 IS 22 BP 6132 EP 6143 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VW418 UT WOS:A1996VW41800013 PM 8947035 ER PT J AU Steingrimsson, E Nii, A Fisher, DE FerreDAmare, AR McCormick, RJ Russell, LB Burley, SK Ward, JM Jenkins, NA Copeland, NG AF Steingrimsson, E Nii, A Fisher, DE FerreDAmare, AR McCormick, RJ Russell, LB Burley, SK Ward, JM Jenkins, NA Copeland, NG TI The semidominant Mi(b) mutation identifies a role for the HLH domain in DNA binding in addition to its role in protein dimerization SO EMBO JOURNAL LA English DT Article DE bHLH-Zip transcription factors; DNA binding; melanocytes; microphthalmia; retinal degeneration ID RECESSIVE RETINITIS-PIGMENTOSA; INHERITED RETINAL DYSTROPHY; MICROPHTHALMIA GENE; TRANSCRIPTION FACTOR; B/HLH/Z DOMAIN; ALPHA-SUBUNIT; HUMAN HOMOLOG; BROWN LOCUS; MOUSE MODEL; ONE FORM AB The mouse microphthalmia (mi) locus encodes a basic helix-loop-helix-leucine zipper (bHLH-Zip) transcription factor called MITF (microphthalmia transcription factor). Mutations at mi affect the development of several different cell types, including melanocytes, mast cells, osteoclasts and pigmented epithelial cells of the eye. Here we describe the phenotypic and molecular characterization of the semidominant Microphthalmia(brownish) (Mi(b)) mutation. We show that this mutation primarily affects melanocytes and produces retinal degeneration. The mutation is a G to A transition leading to a Gly244Glu substitution in helix 2 of the HLH dimerization domain. This location is surprising since other semidominant mi mutations characterized to date have been shown to affect DNA binding or transcriptional activation domains of MITF and act as dominant negatives, while mutations that affect MITF dimerization are inherited recessively. Gel retardation assays showed that while the mutant MITF(Mi-b) protein retains its dimerization potential, it is defective in its ability to bind DNA. Computer modeling suggested that the Gly244Glu mutation might disrupt DNA binding by interfering with productive docking of the protein dimer onto DNA. The Mi(b) mutation therefore appears to dissociate a DNA recognition function of the HLH domain from its role in protein dimerization. C1 NCI,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NCI,OFF LAB ANIM SCI,VET & TUMOR PATHOL SECT,FREDERICK,MD 21702. HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. ROCKEFELLER UNIV,HOWARD HUGHES MED INST,MOL BIOPHYS LAB,NEW YORK,NY 10021. OAK RIDGE NATL LAB,DIV BIOL,OAK RIDGE,TN 37831. NR 43 TC 38 Z9 38 U1 0 U2 2 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 NOV 15 PY 1996 VL 15 IS 22 BP 6280 EP 6289 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VW418 UT WOS:A1996VW41800029 PM 8947051 ER PT J AU Polymeropoulos, MH Ide, SE Magyari, T Francomano, CA AF Polymeropoulos, MH Ide, SE Magyari, T Francomano, CA TI Brachydactyly type C gene maps to human chromosome 12q24 SO GENOMICS LA English DT Article ID LINKAGE AB Brachydactyly type C is an autosomal dominant disorder characterized by abnormal segmentation of the index and middle fingers segregating with a high degree of variable expression in members of the same family. We have followed up and studied members of the large kindred segregating with the brachydactyly type C phenotype described by Virgil Haws in 1963, and using genetic linkage analysis, we localized the susceptibility gene to human chromosome 12q24. (C) 1996 Academic Press, Inc. C1 NIH,NATL CTR HUMAN GENOME RES,MED GENET BRANCH,BETHESDA,MD 20892. RP Polymeropoulos, MH (reprint author), NIH,NATL CTR HUMAN GENOME RES,GENE MAPPING UNIT,LAB GENET DIS RES,BLDG 49,ROOM 4A66,BETHESDA,MD 20892, USA. NR 12 TC 15 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 15 PY 1996 VL 38 IS 1 BP 45 EP 50 DI 10.1006/geno.1996.0590 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VV024 UT WOS:A1996VV02400007 PM 8954778 ER PT J AU Oh, IU Inazawa, J Kim, YO Song, BJ Huh, TL AF Oh, IU Inazawa, J Kim, YO Song, BJ Huh, TL TI Assignment of the human mitochondrial NADP(+)-specific isocitrate dehydrogenase (IDH2) gene to 15q26.1 by in situ hybridization SO GENOMICS LA English DT Article ID ALPHA-SUBUNIT; RAT-LIVER; CHROMOSOME-15; ISOENZYMES; MARKERS; REGION C1 KYUNGPOOK NATL UNIV,COLL NAT SCI,DEPT GENET ENGN,TAEGU 702701,SOUTH KOREA. KYOTO PREFECTURAL UNIV MED,DEPT HYG,KAMIGYO KU,KYOTO 602,JAPAN. NIAAA,NEUROGENET LAB,ROCKVILLE,MD 20852. NR 18 TC 16 Z9 19 U1 1 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 NOV 15 PY 1996 VL 38 IS 1 BP 104 EP 106 DI 10.1006/geno.1996.0602 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VV024 UT WOS:A1996VV02400019 PM 8954790 ER PT J AU Bilski, P Chignell, CF AF Bilski, P Chignell, CF TI Optimization of a pulse laser spectrometer for the measurement of the kinetics of singlet oxygen O-2(Delta(1)(g)) decay in solution SO JOURNAL OF BIOCHEMICAL AND BIOPHYSICAL METHODS LA English DT Article DE germanium diode; NdYag laser; perinaphthenone (phenalenone); Rose Bengal; singlet oxygen; singlet oxygen lifetime; quenching; spectrometer ID MOLECULAR-OXYGEN; ROSE-BENGAL; CATIONIC SURFACTANT; AQUEOUS-SOLUTION; YIELDS; PHOTOSENSITIZATION; PHOTOPROCESSES; SOLVENTS; EOSIN AB A simple sensitive pulse laser spectrometer to measure the kinetics of singlet oxygen decay in solution is described. It utilizes a NdYag laser for pulse excitation of the O-1(2) photosensitizers perinaphthenone and Rose Bengal or eosine at 355 nm and 532 nm, respectively. Singlet oxygen phosphorescence is detected by a germanium diode, to which collimated phosphorescence light is directed by concave and parabolic mirrors via a pair of Fresnel lenses and an infrared interference filter. The O-1(2) transient decays are monitored using a Hewlett Packard digitizing oscilloscope and a PC computer. The excellent sensitivity of this spectrometer allows us to easily observe O-1(2) decay (1 mu s resolution) after a single pulse of laser excitation, which is important for quenching measurements of chemical substrates that react readily with O-1(2). The small sample volume (0.1 ml) prepared in quartz tubes permits fast and inexpensive data acquisition for the determination of O-1(2) quenching rate constants in most solvents. RP Bilski, P (reprint author), NIEHS,MOL BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 23 TC 33 Z9 33 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-022X J9 J BIOCHEM BIOPH METH JI J. Biochem. Biophys. Methods PD NOV 15 PY 1996 VL 33 IS 2 BP 73 EP 80 DI 10.1016/S0165-022X(96)00012-7 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VV666 UT WOS:A1996VV66600002 PM 8951528 ER PT J AU Hendler, RW Mukhopadhyay, AK Smith, PD Cascio, HE AF Hendler, RW Mukhopadhyay, AK Smith, PD Cascio, HE TI A monitoring system for energy transduction by bacteriorhodopsin liposomes SO JOURNAL OF BIOCHEMICAL AND BIOPHYSICAL METHODS LA English DT Article DE membrane potential; delta pH; proton pump; light activation; fluorescence probe; photobleaching of probe; SCN--selective electrode; computer-controlled system ID REAL-TIME MEASUREMENTS; ATP SYNTHESIS; DELTA-PH; OXONOL-V; PROBE; MEMBRANES AB A computer-controlled system and custom software are described that collect information and perform computations to quantify important parameters of energy transduction during the conversion of photons into a proton electrochemical gradient (Delta<(mu)over tilde>(H+)) by bacteriorhodopsin (BR)-liposomes. The strong actinic light used to energize the BR-liposomes causes several serious problems for the approaches commonly used to measure these parameters. This paper identifies these problems and presents solutions that permit the acquisition of the desired information, namely, the initial (1st sec) rate and total extent of H+ translocation, rate of H+ leakage (driven by an existing Delta<(mu)over tilde>(H+)), external, internal and delta pH values, and Delta Psi values. The system is presented with representative experimental data. RP Hendler, RW (reprint author), NHLBI,CELL BIOL LAB,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 10,BETHESDA,MD 20892, USA. NR 12 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-022X J9 J BIOCHEM BIOPH METH JI J. Biochem. Biophys. Methods PD NOV 15 PY 1996 VL 33 IS 2 BP 89 EP 104 DI 10.1016/S0165-022X(96)00017-6 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VV666 UT WOS:A1996VV66600004 PM 8951530 ER PT J AU Quilliam, LA Lambert, QT MickelsonYoung, LA Westwick, JK Sparks, AB Kay, BK Jenkins, NA Gilbert, DJ Copeland, NG Der, CJ AF Quilliam, LA Lambert, QT MickelsonYoung, LA Westwick, JK Sparks, AB Kay, BK Jenkins, NA Gilbert, DJ Copeland, NG Der, CJ TI Isolation of a NCK-associated kinase, PRK2, an SH3-binding protein and potential effector of Rho protein signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID WISKOTT-ALDRICH SYNDROME; EPIDERMAL GROWTH-FACTOR; C-CBL PROTOONCOGENE; TRANSCRIPTIONAL ACTIVATION; SH3 DOMAINS; MOUSE; GENE; PHOSPHORYLATION; RECEPTORS; CELLS AB The NCK adapter protein is comprised of three consecutive Src homology 3 (SH3) protein-protein interaction domains and a C-terminal SH2 domain. Although the association of NCK with activated receptor protein-tyrosine kinases, via its SH2 domain, implicates NCK as a mediator of growth factor-induced signal transduction, little is known about the pathway(s) downstream of NCK. recruitment. To identify potential downstream effecters of NCR we screened a bacterial expression library to isolate proteins that bind its SH3 domains. Two molecules were isolated, the Wiskott-Aldrich syndrome protein (WASP, a putative CDC42 effector) and a serine/threonine protein kinase (PRK2, closely related to the putative Rho effector PKN). Using interspecific backcross analysis the Prk2 gene was mapped to mouse chromosome 3. Unlike WASP, which bound the SH3 domains of several signaling proteins, PRK2 specifically bound to the middle SH3 domain of NCK and (weakly) that of phospholipase C gamma. PRK2 also specifically bound to Rho in a GTP-dependent manner and cooperated with Rho family proteins to induce transcriptional activation via the serum response factor. These data suggest that PRK2 may coordinately mediate signal transduction from activated receptor protein-tyrosine kinases and Rho and that NCK may function as an adapter to connect receptor-mediated events to Rho protein signaling. C1 INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,INDIANAPOLIS,IN 46202. UNIV N CAROLINA,LINEBERGER COMPREHENS CANC CTR,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT PHARMACOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT BIOL,CHAPEL HILL,NC 27599. NCI,MAMMALIAN GENET LAB,ABL,BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. RP Quilliam, LA (reprint author), INDIANA UNIV,SCH MED,DEPT BIOCHEM & MOL BIOL,635 BARNHILL DR,MS 410,INDIANAPOLIS,IN 46202, USA. RI Quilliam, Lawrence/B-6447-2015 FU NCI NIH HHS [CA63139, CA42978, CA52072] NR 43 TC 118 Z9 121 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 NOV 15 PY 1996 VL 271 IS 46 BP 28772 EP 28776 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VT052 UT WOS:A1996VT05200011 PM 8910519 ER PT J AU Mahoney, CW Pak, JH Huang, KP AF Mahoney, CW Pak, JH Huang, KP TI Nitric oxide modification of rat brain neurogranin - Identification of the cysteine residues involved in intramolecular disulfide bridge formation using site-directed mutagenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LONG-TERM POTENTIATION; KINASE-C SUBSTRATE; CALMODULIN-BINDING-PROTEIN; AMINO-ACID-SEQUENCE; RC3 NEUROGRANIN; PHOSPHORYLATION; LOCALIZATION; GLUTAREDOXIN; PEROXYNITRITE; NITROSYLATION AB Neurogranin (Ng) is a neuron-specific protein kinase C-selective substrate, which binds calmodulin (CaM) in the dephosphorylated form at low levels of Ca2+. This protein contains redox active Cys residues that are readily oxidized by several nitric oxide (NO) donors and other oxidants to form intramolecular disulfide. Identification of the Cys residues of rat brain Ng, Cys(3), Cys(4), Cys(9), and Cys(51), involved in NO-mediated intramolecular disulfide bridge formation was examined by site-directed mutagenesis. Mutation of all four Cys residues or single mutation of Cys(51) blocked the oxidant-mediated intramolecular disulfide formation as monitored by the downward mobility shift under nonreducing SDS-polyacrylamide gel electrophoresis. Single mutation of Cys(3), Cys(4), or Cys(9) or double mutation of any pair of these three Cys residues did not block such intramolecular disulfide formation, although the rates of oxidation of these mutant proteins were different. Thus, Cys(51) is an essential pairing partner in NO-mediated intramolecular disulfide formation in Ng. Cys(3), Cys(4), and Cys(9) individually could pair with Cys(51), and the order of reactivity was Cys(9) > Cys(4) > Cys(3), suggesting that Cys(9) and Cys(51) form the preferential disulfide bridge. In all cases tested, the intramolecularly disulfide bridged Ng proteins displayed dramatically attenuated CaM-binding affinity and similar to 2-3-fold weaker protein kinase C substrate phosphorylation activity. The data indicate that the N-terminal Cys(3), Cys(4), and Cys(9) are in close proximity to the C-terminal Cys(51) in solution. The disulfide bridge between the N- and C-terminal domains of Ng renders the central CaM-binding and phosphorylation site domain in a fixed conformation unfavorable for binding to CaM and as a substrate of protein kinase C. C1 NICHHD, METAB REGULAT SECT, ENDOCRINOL & REPROD RES BRANCH, NIH, BETHESDA, MD 20892 USA. NR 39 TC 36 Z9 37 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 15 PY 1996 VL 271 IS 46 BP 28798 EP 28804 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VT052 UT WOS:A1996VT05200015 PM 8910523 ER PT J AU Ohno, H Fournier, MC Poy, G Bonifacino, JS AF Ohno, H Fournier, MC Poy, G Bonifacino, JS TI Structural determinants of interaction of tyrosine-based sorting signals with the adaptor medium chains SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANS-GOLGI NETWORK; TRANSFERRIN RECEPTOR INTERNALIZATION; CYTOPLASMIC DOMAIN; PLASMA-MEMBRANE; COATED PITS; COMPLEX AP-2; AMINO-ACID; CLATHRIN; PROTEINS; ENDOCYTOSIS AB Many integral membrane proteins contain tyrosine-based signals within their cytoplasmic domains that mediate internalization from the cell surface and targeting to lysosomal compartments. internalization depends on an interaction of the tyrosine-based signals with the clathrin-associated adaptor complex AP-2 at the plasma membrane, whereas lysosomal targeting involves interaction of the signals with an analogous complex, AP-1, at the trans-Golgi network. Recent studies have identified the medium chains mu(2) of AP-2 and mu(1) of AP-1 as the recognition molecules for tyrosine-based signals. We have now investigated the structural determinants for interaction of the signals with mu(2) and mu(1). The position of the signals was found to be an important determinant of interactions with mu(2) and mu(1); signals were most effective when present at the carboxyl terminus of a polypeptide sequence. Another important determinant of interactions was the identity of residues surrounding the critical tyrosine residue. Mutation of some residues affected interactions with mu(2) and mu(1) similarly, whereas other mutations had differential effects. These observations suggest that both the position and the exact sequence of tyrosine-based sorting signals are major determinants of selectivity in their interaction with clathrin-associated adaptor complexes. C1 NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892. NIDDK,GENET & BIOCHEM BRANCH,NIH,BETHESDA,MD 20892. RI Ohno, Hiroshi/L-7899-2014; OI Ohno, Hiroshi/0000-0001-8776-9661; Bonifacino, Juan S./0000-0002-5673-6370 NR 45 TC 240 Z9 241 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 15 PY 1996 VL 271 IS 46 BP 29009 EP 29015 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VT052 UT WOS:A1996VT05200044 PM 8910552 ER PT J AU Froelich, CJ Orth, K Turbov, J Seth, P Gottlieb, R Babior, B Shah, GM Bleackley, RC Dixit, VM Hanna, W AF Froelich, CJ Orth, K Turbov, J Seth, P Gottlieb, R Babior, B Shah, GM Bleackley, RC Dixit, VM Hanna, W TI New paradigm for lymphocyte granule-mediated cytotoxicity - Target cells bind and internalize granzyme B, but an endosomolytic agent is necessary for cytosolic delivery and subsequent apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA FRAGMENTATION; LYSIS; INHIBITION; PROTEASES; PERFORIN; PHOSPHATIDYLSERINE; PURIFICATION; ADENOVIRUS; POLYMERASE; PATHWAYS AB Lymphocyte granule-mediated apoptosis is postulated to entail the formation of membrane pores by perforin. Then soluble granzyme reaches the cytosol either through these pores or by reparative pinocytosis. We demonstrate here that Jurkat cells bind and internalize granzyme B via high affinity binding sites without toxic consequence. Apoptosis occurs, however, if sublytic perforin is added to targets washed free of soluble granzyme B, We suggest that granule-mediated apoptosis mimics viral strategies for cellular entry. Accordingly, co-internalization of granzyme B with adenovirus, a virus that escapes endosomes to reach the cytosol, also induced apoptosis. Poly(ADP-ribose) polymerase cleavage and processing of CPP32, ICE-LAP3, and Mch2 were detected at 30 min, while cytosolic acidification and DNA fragmentation occurred at 60 min. Annexin V binding and membrane permeabilization arose at 4 h. The concurrent activation of the Ced-3 proteases differed from the rate at which each cysteine protease is cleaved in vitro by granzyme B. Thus, granzyme B may not directly process these proteases in whole cells but rather may function by activating a more proximal enzyme. These results indicate that adenovirus-mediated delivery of granzyme B is suitable for elucidating biochemical events that accompany granule-mediated apoptosis. C1 NORTHWESTERN UNIV, EVANSTON HOSP, DEPT MED, EVANSTON, IL 60201 USA. UNIV MICHIGAN, SCH MED, DEPT PATHOL, ANN ARBOR, MI 48109 USA. NCI, MED BRANCH, NIH, BETHESDA, MD 20892 USA. SCRIPPS RES INST, DIV BIOCHEM, SAN DIEGO, CA 92037 USA. UNIV LAVAL, HOSP & RES CTR, UNIT HLTH & ENVIRONM, POLY ADP RIBOSE METAB GRP, QUEBEC CITY, PQ G1V 4G2, CANADA. UNIV ALBERTA, DEPT BIOCHEM, EDMONTON, AB T6G 2H7, CANADA. RI Shah, Girish/A-5153-2008; dixit, vishva/A-4496-2012 OI dixit, vishva/0000-0001-6983-0326 FU NCI NIH HHS [CA68769]; NIA NIH HHS [AG-13501] NR 42 TC 281 Z9 287 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 15 PY 1996 VL 271 IS 46 BP 29073 EP 29079 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VT052 UT WOS:A1996VT05200053 PM 8910561 ER PT J AU Ahmed, SA McPhie, P Miles, EW AF Ahmed, SA McPhie, P Miles, EW TI Mechanism of activation of the tryptophan synthase alpha(2)beta(2) complex - Solvent effects of the co-substrate beta-mercaptoethanol SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ULTRAVIOLET VISIBLE SPECTROSCOPY; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; BIENZYME COMPLEX; L-SERINE; ASPARTATE-AMINOTRANSFERASE; 3-DIMENSIONAL STRUCTURE; ALLOSTERIC INTERACTIONS; 10-18-PPM RANGE; H-1 RESONANCES AB To characterize the conformational transitions that lead to activation of catalysis by the tryptophan synthase alpha(2) beta(2), complex, we have determined the solvent effects of a co-substrate, beta-mercaptoethanol, and of a model nonsubstrate, ethanol, on the catalytic and spectroscopic properties of the enzyme. Our results show that ethanol and beta-mercaptoethanol both alter the equilibrium distribution of pyridoxal 5'-phosphate intermediates formed in the reactions of L-serine at the beta site in the alpha(2) beta(2) complex. Addition of increasing concentrations of ethanol increases the proportion of the external aldimine of L-serine and decreases the proportion of the external aldimine of aminoacrylate. Low concentrations of the co-substrate beta-mercaptoethanol (K-d = similar to 13 mM) decrease the proportion of the external aldimine of aminoacrylate and induce formation of the quinonoid of S-hydroxyethyl-L-cysteine. Higher concentrations of beta-mercaptoethanol decrease the concentration of the quinonoid intermediate and increase the proportion of the external aldimine of L-serine. Data analysis shows that beta-mercaptoethanol and ethanol both interact or bind preferentially with the conformer of the enzyme that predominates when the aldimine of L-serine is formed and shift the equilibrium in favor of this conformer. We propose that a nonpolar region of the beta subunit, possibly the hydrophobic indole tunnel, becomes less exposed to solvent in the conformational transition that activates the alpha(2) beta(2) complex. C1 NIDDK, BIOCHEM PHARMACOL LAB, NIH, BETHESDA, MD 20892 USA. NR 58 TC 20 Z9 20 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 15 PY 1996 VL 271 IS 46 BP 29100 EP 29106 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VT052 UT WOS:A1996VT05200057 PM 8910565 ER PT J AU Aman, MJ Tayebi, N Obiri, NI Puri, RK Modi, WS Leonard, WJ AF Aman, MJ Tayebi, N Obiri, NI Puri, RK Modi, WS Leonard, WJ TI cDNA cloning and characterization of the human interleukin 13 receptor alpha chain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SEQUENCE CLEAVAGE SITES; LIGAND-BINDING; GAMMA-CHAIN; B-CELLS; CYTOKINE; EXPRESSION; MONOCYTES; SUBUNITS; IL-4 AB We have cloned cDNAs corresponding to the human interleukin 13 receptor alpha chain (IL-13R alpha). The protein has 76% homology to murine IL-13R alpha, with 95% amino acid identity in the cytoplasmic domain. Only weak IL-13 binding activity was found in cells transfected with only IL-13R alpha; however, the combination of both IL-13R alpha and IL-4R alpha resulted in substantial binding activity, with a K-d of approximately 400 pM, indicating that both chains are essential components of the IL-13 receptor. Whereas IL-13R alpha serves as an alternative accessory protein to the common cytokine receptor gamma chain (gamma(c)) for IL-4 signaling, it could not replace the function of gamma(c) in allowing enhanced IL-2 binding activity. Nevertheless, the overall size and length of the cytoplasmic domain of IL-13R alpha and gamma(c) are similar, and like gamma(c), IL-13R alpha is located on chromosome X. C1 NHLBI,LAB MOL IMMUNOL,NIH,BETHESDA,MD 20892. NIMH,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,FREDERICK,MD 21702. NR 28 TC 243 Z9 251 U1 2 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 15 PY 1996 VL 271 IS 46 BP 29265 EP 29270 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VT052 UT WOS:A1996VT05200078 PM 8910586 ER PT J AU Baumert, TF Rogers, SA Hasegawa, K Liang, TJ AF Baumert, TF Rogers, SA Hasegawa, K Liang, TJ TI Two core promotor mutations identified in a hepatitis B virus strain associated with fulminant hepatitis result in enhanced viral replication SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE core promotor; encapsidation; HBX gene ID X-PROTEIN; REVERSE TRANSCRIPTION; MESSENGER-RNA; DNA-SYNTHESIS; GENE; ENCAPSIDATION; TRANSLATION; BINDING; HEPADNAVIRUS; INITIATION AB Viral mutations have been implicated in alteration of the biological phenotype of hepatitis B virus (HBV). We recently cloned and sequenced the viral genome of an HBV strain associated with an outbreak of fulminant hepatitis (FH strain). The FH strain contained numerous mutations in all genomic regions and was functionally characterized by a more efficient encapsidation of pregenomic RNA leading to highly enhanced replication, To define the responsible mutation(s) for the enhanced replication, we introduced individual mutations of the FH strain into a wild-type construct by oligonucleotide-directed mutagenesis, Analysis of viral replication showed that two adjacent mutations in the HBV core promotor (C to T at nucleotide 1768 and T to A at nucleotide 1770) led to high level replication, Similar to the FH strain, this mutant displayed the phenotype of enhanced encapsidation of pregenomic RNA. Functional studies in an encapsidation assay demonstrated that the identified mutations resulted in a minor increase of pregenomic RNA transcription (two- to threefold) and a major transcription-independent enhancement (> 10-fold) of viral encapsidation, Our results demonstrate that the two adjacent mutations in the HBV core promotor region are responsible for the enhanced replication of the FH strain, These two mutations, outside the previously described encapsidation signal, core, and polymerase polypeptides, appeared to affect a novel genetic element involved in viral encapsidation. C1 NIDDK,LIVER DIS SECT,NIH,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,DEPT MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NCI NIH HHS [CA-54524]; NIDDK NIH HHS [DK-01952, VF-DK-14361] NR 40 TC 142 Z9 152 U1 1 U2 7 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 NOV 15 PY 1996 VL 98 IS 10 BP 2268 EP 2276 DI 10.1172/JCI119037 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VU826 UT WOS:A1996VU82600013 PM 8941643 ER PT J AU Thompson, DB Pratley, R Ossowski, V AF Thompson, DB Pratley, R Ossowski, V TI Human primary myoblast cell cultures from non-diabetic insulin resistant subjects retain defects in insulin action SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE myoblast; insulin; glycogen; cell culture; skeletal muscle ID SKELETAL-MUSCLE CELLS; GLUCOSE-TRANSPORT; PIMA-INDIANS; MELLITUS; NIDDM AB Insulin resistance is a predictor of the development of noninsulin-dependent diabetes mellitus (NIDDM) in humans. It is unclear whether insulin resistance is a primary defect leading to NIDDM or the result of hyperinsulinemia and hyperglycemia. To determine if insulin resistance is the result of extrinsic factors such as hyperinsulinemia primary skeletal muscle cell cultures were established from muscle biopsies from Pima Indians with differing in vivo insulin sensitivities, These cell cultures expressed a variety of muscle-specific phenotypes including the proteins alpha-actinin and myosin, muscle-specific creatine kinase activity, and RNA encoding GLUT4, MYF5, MYOD1, and MYOGENIN. Labeled glucose was used to measure the insulin-stimulated conversion of glucose to glycogen in these cultures, The in vivo rates of insulin-stimulated glycogen production (insulin resistance) were correlated with in vitro measures of glycogen production (P = 0.007, r = 0.58). This defect in insulin action is stable in a uniform culture environment and is retained over time, The retention of insulin resistance in myoblast derived cell cultures is consistent with the expression of an underlying biochemical defect in insulin resistant skeletal muscle. RP Thompson, DB (reprint author), NIDDKD,CLIN DIABET & NUTR SECT,NIH,4212 N 16TH ST,PHOENIX,AZ 85016, USA. NR 20 TC 37 Z9 37 U1 0 U2 1 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 NOV 15 PY 1996 VL 98 IS 10 BP 2346 EP 2350 DI 10.1172/JCI119046 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VU826 UT WOS:A1996VU82600022 PM 8941652 ER PT J AU Shirai, M Kurokohchi, K Pendleton, CD Arichi, T Boyd, LF Takahashi, H Margulies, DH Berzofsky, JA AF Shirai, M Kurokohchi, K Pendleton, CD Arichi, T Boyd, LF Takahashi, H Margulies, DH Berzofsky, JA TI Reciprocal cytotoxic T lymphocyte cross-reactivity interactions between two major epitopes within HIV-1 gp160 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS ENVELOPE; SURFACE-PLASMON RESONANCE; CLASS-I MOLECULES; HISTOCOMPATIBILITY COMPLEX; PEPTIDE BINDING; SYNTHETIC PEPTIDES; MHC MOLECULE; SEROPOSITIVE INDIVIDUALS; ANTIGEN RECOGNITION; CELL RECOGNITION AB We have observed and analyzed an unexpected cross-reactivity oi CD8(+) CTL between two nonhomologous peptides of the HIV-1 IIIB gp160 envelope protein, P18 (residues 315-329) and HP53 (834-848, also called TH4,1), in the context of four different class I MHC molecules, D-d, D-p, D-q (Or L(q)), and H-2(u). In strains expressing D-d, the cross-reactivity between peptides was bidirectional, whereas in other strains (H-2(u), H-2(p), and H-2(q)), the cross-reactivity was unidirectional; that is, P18-specific CTLs showed no killing against targets pulsed with HP53, although HP53 stimulated CTL showed cross-reactive lysis against P1B-pulsed target cells. Cross-reactivity was also shown in immunization in viva and with target cells endogenously expressing viral protein in vitro using two different recombinant vaccinia viruses expressing only the N-terminal portion of gp160, containing P18 but not HP53, Peptide cross-contamination was excluded, Cold target inhibition and single cell cloning experiments indicated that the same CTL was responding to both peptides. Using substituted and truncated peptides, we explored amino acid residues critical for cross-reactive CTL recognition, identified fine specificity similarities among all cross-reactive CTL lines but not non-cross-reactive lines, and mapped cross-reactivity to a 10-residue core of P18 and to an eight-residue core of HP53, A comparison of these peptide sequences and recent data on residues of P18 interacting with H-2D(d) provided us with clues to residues involved in the interaction of the CTL with the MHC-peptide complex. C1 NCI,MOL IMMUNOGENET & VACCINE RES SECT,METAB BRANCH,NIH,BETHESDA,MD 20892. NIAID,MOL BIOL SECT,IMMUNOL LAB,NIH,BETHESDA,MD 20892. YAMAGUCHI UNIV,SCH MED,DEPT MICROBIOL,UBE,YAMAGUCHI 755,JAPAN. NIPPON MED COLL,DEPT MICROBIOL & IMMUNOL,BUNKYO KU,TOKYO 113,JAPAN. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 51 TC 13 Z9 13 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 NOV 15 PY 1996 VL 157 IS 10 BP 4399 EP 4411 PG 13 WC Immunology SC Immunology GA VR793 UT WOS:A1996VR79300018 PM 8906815 ER PT J AU Amichay, D Gazzinelli, RT Karupiah, G Moench, TR Sher, A Farber, JM AF Amichay, D Gazzinelli, RT Karupiah, G Moench, TR Sher, A Farber, JM TI Genes for chemokines MuMig and Crg-2 induced in protozoan and viral infections in response to IFN-gamma with patterns of tissue expression that suggest nonredundant roles in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERFERON-INDUCIBLE PROTEIN-10; T-CELLS; FUNCTIONAL-CHARACTERIZATION; TOXOPLASMA-GONDII; IN-VIVO; MICE; CYTOKINES; RECEPTOR; CHEMOATTRACTANT; IDENTIFICATION AB MuMig and Crg-2 are IFN-inducible murine chemokines whose human homologues, MuMig and IP-10, respectively, share activity in vitro as T cell chemoattractants. We analyzed the expression of the genes Mumig, crg-2, and IFN-gamma during experimental infections with Plasmodium yoelii, Toxoplasma gondii, and vaccinia virus. Mumig, crg-2 and IFN-gamma were induced in multiple organs. During the acute phase of each infection as well as after i.p. injection of rIFN-gamma, levels of Mumig mRNA in the liver were as high or higher than levels in any of the other organs. In contrast, the organs showing the highest expression of crg-2 and IFN-gamma varied among the experimental models, with induction of these latter two genes colocalizing. Differences in relative levels of expression of Mumig and crg-2 in liver and spleen were not demonstrably due to expression of the genes in different cell types within these organs. We showed that both Mumig and crg-2 are induced in the liver in hepatocytes and in the spleen in CD11b(+) cells. IFN-gamma was necessary for induction of Mumig during infections with T. gondii or vaccinia virus. In contrast, induction of crg-2 was not completely dependent on IFN-gamma. These data demonstrate that despite the overlap in activities within chemokine subsets, chemokine genes show differences in their patterns of expression and in their responses to inducers that suggest nonredundant roles in vivo. Moreover, the pattern of induction of crg-2 is consistent with Crg-2 acting primarily locally, while the pattern for Mumig induction suggests that Mumig induction suggests that MuMig may have a systemic role during infection. C1 NIAID,CLIN INVEST LAB,NIH,BETHESDA,MD 20892. NIAID,IMMUNOBIOL SECT,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. RI Karupiah, Gunasegaran/J-4707-2013 NR 45 TC 126 Z9 128 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 NOV 15 PY 1996 VL 157 IS 10 BP 4511 EP 4520 PG 10 WC Immunology SC Immunology GA VR793 UT WOS:A1996VR79300032 PM 8906829 ER PT J AU Pericle, F Sconocchia, G Titus, JA Segal, DM AF Pericle, F Sconocchia, G Titus, JA Segal, DM TI CD44 is a cytotoxic triggering molecule on human polymorphonuclear cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; ANTI-TARGET CELL; FC-GAMMA-RI; CYTOPLASMIC DOMAIN; LYMPHOCYTES-T; COLORIMETRIC ASSAY; HYALURONAN-BINDING; CYTOLYTIC ACTIVITY; EFFECTOR-CELLS; RECEPTOR AB In this study, we present evidence that CD44 is a cytotoxic triggering molecule on freshly isolated polymorphonuclear cells (PMN). PMN constitutively express high levels of CD44 as determined by FAGS analysis, and immunoprecipitation studies using PMN lysates and an anti-CD44 mAb show a band of 80 to 90 kDa that migrates slightly faster than CD44 from PBL. A bispecific Ab consisting of anti-CD44 Fab cross-linked to anti-DNP Fab (anti-CD44(Fab) x anti-DNP(Fab)) induces PMN to lyse DNP-coated tumor cells in an 18-h assay, and this lysis is specifically inhibited by a polyclonal anti-CD44 F(ab')(2). A second bispecific Ab, anti-CD16(Fab) x anti-DNP(Fab), that binds to Fc gamma RIIIb on PMN does not induce lysis, indicating that the bridging of target cells to PMN per se is not sufficient for killing. Moreover, CD44-directed killing by PMN results in the lysis of bystander cells, suggesting that the mechanisms of tumor cytolysis by CD44-targeted PMN does not require cell-cell contact. Lastly, PMN lyse target cells coated with hyaluronic acid (HA), the principal ligand for CD44, and this cytolytic activity is specifically blocked by the polyclonal anti-CD44 F(ab')(2) and by an anti-CD44 mAb. We suggest that the interaction of HA with CD44 on neutrophils might initiate cytotoxic or inflammatory responses in vivo when neutrophils encounter high amounts of HA, for example on tumor cells, or in the extracellular matrix. C1 NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NR 44 TC 24 Z9 25 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 NOV 15 PY 1996 VL 157 IS 10 BP 4657 EP 4663 PG 7 WC Immunology SC Immunology GA VR793 UT WOS:A1996VR79300049 PM 8906846 ER PT J AU Bailey, MF Davidson, BE Minton, AP Sawyer, WH Howlett, GJ AF Bailey, MF Davidson, BE Minton, AP Sawyer, WH Howlett, GJ TI The effect of self-association on the interaction of the Escherichia coli regulatory protein TyrR with DNA SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE DNA-protein interactions; sedimentation equilibrium; TyrR; heterogeneous associations; analytical ultracentrifugation ID ANALYTICAL ULTRACENTRIFUGATION; NUCLEOTIDE-SEQUENCE; MEDIATED REPRESSION; BINDING DOMAIN; TRP REPRESSOR; MTR GENE; ACTIVATION; EXPRESSION; K-12; TYROSINE AB The interaction of the Escherichia coli regulatory protein TyrR, with a 42 bp oligonucleotide (42A/42B) containing a centrally located recognition sequence (TyrR box), was examined by analytical ultracentrifugation. The stoichiometry of the binding of oligonucleotide to dimeric TyrR was determined by equilibrium centrifugation of a mixture of fluorescein-5-isothiocyanate-labelled 42A/42B (F-42A/42B) in the presence of an eightfold molar excess of TyrR. The molecular mass (M) of the labelled oligonucleotide was estimated as 148,000, indicating a 1:1 complex composed of oligonucleotide (M = 27,000) and TyrR dimer (M = 113,000). The association constant (K-o,K-d = 2.8(+/-0.1) x 10(6) M(-1)) was determined by a global analysis of sedimentation data, collected at multiple wavelengths between 230 and 285 nm. The presence of 30 mu M ATP gamma S enhanced the affinity of TyrR for DNA approximately 3.5-fold, (K-o,K-d = 9.9(+/-0.3) x 10(6) M(-1)). The effect of dimer to hexamer self-association of TyrR on the binding of 42A/42B was also examined. Multiple wavelength sedimentation data fitted a model in which the oligonucleotide could bind to one site on the dimer (k(o,d) = 9.9 x 10(6) M(-1)), and to either one or three sites on the hexamer (K-o,K-h = 2.0(+/-0.1) x 10(8) M(-1) and 3.8(+/-0.1) x 10(6) M(-1), respectively). Competitive sedimentation equilibrium and fluorescence anisotropy titrations were performed under stoichiometric conditions to resolve the number of oligonucleotide binding sites per hexamer. In these experiments, 42A/42B was used as a competitor to displace F-42A/42B from the hexamer, which was found to bind the 42mer with a 1:1 stoichiometry. Our data support a model in which ATP increases the affinity of TyrR for the DNA recognition sequence, and tyrosine induced self-association of TyrR generates a hexameric species with a single binding site for the 42A/42B oligonucleotide. (C) 1996 Academic Press Limited C1 UNIV MELBOURNE,RUSSELL GRIMWADE SCH BIOCHEM & MOL BIOL,PARKVILLE,VIC 3052,AUSTRALIA. NIDDKD,BIOCHEM PHARMACOL LAB,NATL INST HLTH,BETHESDA,MD 20892. NR 40 TC 37 Z9 38 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 15 PY 1996 VL 263 IS 5 BP 671 EP 684 DI 10.1006/jmbi.1996.0607 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VT337 UT WOS:A1996VT33700005 PM 8947567 ER PT J AU Liu, MW Max, MB Parada, S Rowan, JS Bennett, GJ AF Liu, MW Max, MB Parada, S Rowan, JS Bennett, GJ TI The sympathetic nervous system contributes to capsaicin-evoked mechanical allodynia but not pinprick hyperalgesia in humans SO JOURNAL OF NEUROSCIENCE LA English DT Article DE sympathetic nervous system; mechanical allodynia; mechanical hyperalgesia; capsaicin; phentolamine; pain ID INDUCED SECONDARY HYPERALGESIA; MAINTAINED PAIN; POSTGANGLIONIC NEURON; ADRENERGIC EXCITATION; HAIRY SKIN; NOCICEPTORS; RAT; PHENTOLAMINE; INJURY; ACTIVATION AB The contribution of the sympathetic nervous system (SNS) to pain, mechanical allodynia (MA), and hyperalgesia in humans is controversial. A clearer understanding is crucial to guide therapeutic use of sympatholytic surgery, blocks, and drug treatments. In rats, capsaicin-evoked MA, and to some extent, pinprick hyperalgesia (PPH), can be blocked with alpha-adrenoreceptor antagonists. In this study, we examined the contribution of the SNS to MA and PPH in normal human subjects by blocking alpha-adrenoreceptors with intravenous phentolamine. In a double-blinded, placebo-controlled, crossover study, subjects were given IV saline or phentolamine, 1 mg/kg over 20 min. Ten minutes after the start of the infusion, subjects received 100 mu g of intradermal capsaicin on the foot dorsum with the temperature of the injected site clamped at 36 degrees C. The temperature of the uninjected foot was used to monitor the degree of cv-adrenoreceptor blockade produced by phentolamine. Ongoing pain and MA and PPH areas were measured every 5 min for 60 min. A significantly greater increase in temperature on the uninjected foot was seen during the phentolamine infusion compared with the saline infusion, indicating alpha-adrenergic blockade. Significantly less MA was observed with the phentolamine infusion 10-25 min after capsaicin injection than with the saline infusion. No significant differences in ongoing pain or PPH areas were seen between the two infusions at any time. Our results suggest that capsaicin-evoked MA and PPH have different mechanisms, with the SNS having a role in MA but not in PPH or ongoing pain. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,NIH,BETHESDA,MD 20892. NIH,CLIN CTR NURSING,BETHESDA,MD 20892. HOSP UNIV PENN,DEPT ANESTHESIA,PHILADELPHIA,PA 19104. NR 39 TC 37 Z9 37 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 NOV 15 PY 1996 VL 16 IS 22 BP 7331 EP 7335 PG 5 WC Neurosciences SC Neurosciences & Neurology GA VR621 UT WOS:A1996VR62100021 PM 8929439 ER PT J AU Maccaferri, G McBain, CJ AF Maccaferri, G McBain, CJ TI The hyperpolarization-activated current (I-h) and its contribution to pacemaker activity in rat CA1 hippocampal stratum oriens-alveus interneurones SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID VOLTAGE-CLAMP ANALYSIS; THALAMIC RELAY NEURONS; SINOATRIAL NODE CELLS; CATION CURRENT; ANOMALOUS RECTIFICATION; INHIBITORY NEURONS; POTASSIUM; NUCLEUS; REGION; INVITRO AB 1. The hyperpolarization-activated current (I-h) and its role in pacemaking activity in rat hippocampal stratum oriens-alveus interneurones was studied using whole-cell and perforated patch-clamp configurations. 2. Voltage-clamp recordings revealed I-h as a slowly activating, inward current, activated by hyperpolarizing steps (holding potential, V-h = -40 mV), with a reversal potential close to -30 mV. Its activation curve ranged from similar to-50 to -120 mV with a mid-activation point of -84.1 mV. 3. I-h was blocked by external application of Cs+ (2-5 mM) and ZD7288 (100 mu M), but not by Ba2+(1 mM). 4. I-h was potentiated by both noradrenaline and isoprenaline by a mechanism consistent with a shift in the I-h activation curve. 5. Under current-clamp conditions (V-h = -60 mV), ZD7288 induced a membrane hyperpolarization concomitant with an increase in the membrane input resistance and abolished the voltage sag generated by hyperpolarizing current injection. 6. Analysis of the current-discharge relationship revealed that block of I-h differentially increased the firing frequency of spikes occurring early in the train compared with those occurring late in the discharge. 7. When applied to spontaneously firing cells, ZD7288 reduced the firing frequency by selectively altering the time course of the interspike interval, while minimally affecting other action potential characteristics. Similarly, isoprenaline increased the spontaneous firing frequency by an effect exclusively on the after hyperpolarization and interspike interval. 8. These results provide evidence for the involvement of I-h in the excitability and generation of spontaneous firing in hippocampal stratum oriens-alveus interneurones. C1 NICHHD,UNIT CELLULAR & SYNAPT PHYSIOL,LAB CELLULAR & MOL NEUROPHYSIOL,BETHESDA,MD 20892. NR 39 TC 280 Z9 280 U1 0 U2 7 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 NOV 15 PY 1996 VL 497 IS 1 BP 119 EP 130 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA VX040 UT WOS:A1996VX04000012 PM 8951716 ER PT J AU Tsuji, H Venditti, FJ Manders, ES Evans, JC Larson, MG Feldman, CL Levy, D AF Tsuji, H Venditti, FJ Manders, ES Evans, JC Larson, MG Feldman, CL Levy, D TI Determinants of heart rate variability SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; ACUTE MYOCARDIAL-INFARCTION; RATE SPECTRAL-ANALYSIS; CARDIAC AUTONOMIC NEUROPATHY; FREQUENCY-DOMAIN MEASURES; PERIOD VARIABILITY; SHORT-TERM; HYPERTROPHIC CARDIOMYOPATHY; VENTRICULAR ARRHYTHMIAS; RR VARIABILITY AB Objectives. This study sought to examine clinical determinants of heart rate variability and to report normative reference values for eight heart rate variability measures. Background. Although the clinical implications of heart rate variability have been described, clinical determinants and normative values of heart rate variability measures have not been studied systematically in a large community-based population. Methods. The first 2 h of ambulatory electrocardiographic recordings obtained in Framingham Heart Study subjects attending a routine examination were reprocessed for heart rate variability, Recordings with transient or persistent nonsinus rhythm, premature beats >10% of total beats, <1-h recording time or processed time <50% of recorded time were excluded; subjects receiving antiarrhythmic medications also were excluded. Among five frequency domain and three time domain measures that were obtained, low frequency power (0.04 to 0.15 Hz), high frequency power (0.15 to 0.40 Hz) and the standard deviation of total normal RR intervals based on 2-h recordings were selected for the principal analyses. Variables with potential physiologic effects or possible technical influences on heart rate variability measures were chosen for multiple linear regression analysis, Normative values, derived from a subset of healthy subjects, were adjusted for age and heart rate. Results. There were 2,722 eligible subjects with a mean age (+/-SD) of 55 +/- 14 years. Three separate multiple linear regression analyses revealed that higher heart rate, older age, beta-adrenergic blocking agent use, history of myocardial infarction or congestive heart failure, diuretic use, diastolic blood pressure greater than or equal to 90 mm Hg, diabetes mellitus, consumption of three or more cups of coffee per day and smoking were associated with lower values of one or more heart rate variability measures, whereas longer processed time, start time in the morning, frequent su praventricular and ventricular premature beats, female gender and systolic blood pressure greater than or equal to 160 mm Hg were associated with higher values. Age and heart rate were the major determinants of all three selected heart rate variability measures (partial R(2) values 0.125 to 0.389). Normative reference values for all eight heart rate variability measures are presented. Conclusions. Age and heart rate must be taken into account when assessing heart rate variability. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA 01701. KANSAI MED UNIV,OSAKA,JAPAN. LAHEY CLIN MED CTR,BURLINGTON,MA 01803. BOSTON UNIV,SCH MED,DIV EPIDEMIOL,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DIV PREVENT MED,BOSTON,MA 02118. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. NHLBI,NIH,BETHESDA,MD 20892. BETH ISRAEL HOSP,DIV CARDIOL & CLIN EPIDEMIOL,BOSTON,MA 02215. NR 42 TC 187 Z9 191 U1 2 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 15 PY 1996 VL 28 IS 6 BP 1539 EP 1546 DI 10.1016/S0735-1097(96)00342-7 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA VT310 UT WOS:A1996VT31000015 PM 8917269 ER PT J AU Li, CY Peoples, RW Weight, FF AF Li, CY Peoples, RW Weight, FF TI Cu2+ potently enhances ATP-activated current in rat nodose ganglion neurons SO NEUROSCIENCE LETTERS LA English DT Article DE copper; ATP; ion channels; P-2X purinoceptors; zinc; proton; neuron; modulation ID CENTRAL-NERVOUS-SYSTEM; MAMMALIAN NEURONS; SYNAPTIC TRANSMISSION; CHANNELS; RECEPTOR; COPPER; CELLS; BRAIN; ZINC AB Several lines of evidence suggest a physiological role for Cu2+ in regulating nervous system function. In the present study using whole-cell patch-clamp recording, Cu2+ greatly enhanced current activated by 10 mu M ATP in the majority of rat nodose ganglion neurons. The enhancement was concentration-dependent between 1 and 50 mu M Cu2+, and had an EC(50) of 6.1 mu M. Cu2+ shifted the ATP concentration-response curve to the left in a parallel manner. However, Cu2+ did not enhance ATP-activated current in the presence of a maximally-effective concentration of Zn2+. The observations suggest that Cu2+ increases the affinity of the receptor for ATP by acting at the Zn2+ modulatory site. In addition, a subset of neurons in the nodose ganglion express ATP-gated receptor-channels that are insensitive to modulation by physiological concentrations of Cu2+, Zn2+ and protons. RP Li, CY (reprint author), NIAAA,MOL & CELLULAR NEUROBIOL LAB,NIH,BETHESDA,MD 20892, USA. NR 21 TC 31 Z9 31 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV 15 PY 1996 VL 219 IS 1 BP 45 EP 48 DI 10.1016/S0304-3940(96)13186-4 PG 4 WC Neurosciences SC Neurosciences & Neurology GA VV380 UT WOS:A1996VV38000012 PM 8961300 ER PT J AU Dean, M Carrington, M Goedert, J OBrien, SJ AF Dean, M Carrington, M Goedert, J OBrien, SJ TI Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene (vol 273, pg 1856, 1996) SO SCIENCE LA English DT Correction, Addition C1 NCI,SCI APPLICAT INT CORP,FREDERICK,MD 21701. NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP Dean, M (reprint author), NCI,LAB GENOM DIVERS,FREDERICK,MD 21702, USA. NR 2 TC 51 Z9 51 U1 1 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 15 PY 1996 VL 274 IS 5290 BP 1069 EP 1069 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VT335 UT WOS:A1996VT33500008 ER PT J AU Taylor, SI Barr, V Reitman, M AF Taylor, SI Barr, V Reitman, M TI Medicine - Does leptin contribute to diabetes caused by obesity? SO SCIENCE LA English DT Editorial Material ID GENE-PRODUCT; PROTEIN RP Taylor, SI (reprint author), NIDDKD,DIABET BRANCH,BETHESDA,MD 20892, USA. RI Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 NR 15 TC 52 Z9 53 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 15 PY 1996 VL 274 IS 5290 BP 1151 EP 1152 DI 10.1126/science.274.5290.1151 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VT335 UT WOS:A1996VT33500040 PM 8966588 ER PT J AU Polymeropoulos, MH Higgins, JJ Golbe, LI Johnson, WG Ide, SE DiIorio, G Sanges, G Stenroos, ES Pho, LT Schaffer, AA Lazzarini, AM Nussbaum, RL Duvoisin, RC AF Polymeropoulos, MH Higgins, JJ Golbe, LI Johnson, WG Ide, SE DiIorio, G Sanges, G Stenroos, ES Pho, LT Schaffer, AA Lazzarini, AM Nussbaum, RL Duvoisin, RC TI Mapping of a gene for Parkinson's disease to chromosome 4q21-q23 SO SCIENCE LA English DT Article ID MITOCHONDRIAL-DNA; COMPLEX; LINKAGE; HUMANS; DEFECT AB Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, affecting approximately 1 percent of the population over age 50. Recent studies have confirmed significant familial aggregation of PD and a large number of large multicase families have been documented. Genetic markers on chromosome 4q21-q23 were found to be linked to the PD phenotype in a large kindred with autosomal dominant PD, with a Z(max) = 6.00 for marker D4S2380. This finding will facilitate identification of the gene and research on the pathogenesis of PD. C1 NINCDS,CLIN NEUROGENET UNIT,MED NEUROL BRANCH,NIH,BETHESDA,MD 20892. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,PISCATAWAY,NJ 08854. UNIV NAPLES 2,FAC MED,IST SCI NEUROL,NAPLES,ITALY. RP Polymeropoulos, MH (reprint author), NIH,LAB GENET DIS RES,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892, USA. RI Schaffer, Alejandro/F-2902-2012 NR 34 TC 460 Z9 493 U1 1 U2 17 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 15 PY 1996 VL 274 IS 5290 BP 1197 EP 1199 DI 10.1126/science.274.5290.1197 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VT335 UT WOS:A1996VT33500055 PM 8895469 ER PT J AU Foulkes, MA Dixon, DO DeGruttola, V Self, S AF Foulkes, MA Dixon, DO DeGruttola, V Self, S TI Symposium on statistical issues in HIV/AIDS research - Preface SO STATISTICS IN MEDICINE LA English DT Editorial Material C1 HARVARD UNIV,SCH PUBL HLTH,CAMBRIDGE,MA 02138. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. RP Foulkes, MA (reprint author), NIAID,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 15 PY 1996 VL 15 IS 21-22 BP 2269 EP 2270 DI 10.1002/(SICI)1097-0258(19961115)15:21<2269::AID-SIM466>3.0.CO;2-R PG 2 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA VQ193 UT WOS:A1996VQ19300001 ER PT J AU Killen, JY AF Killen, JY TI Symposium on statistical issues in HIV/AIDS research - Introduction SO STATISTICS IN MEDICINE LA English DT Editorial Material RP Killen, JY (reprint author), NIAID,DIV AIDS,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 15 PY 1996 VL 15 IS 21-22 BP 2271 EP 2272 PG 2 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA VQ193 UT WOS:A1996VQ19300002 ER PT J AU Gail, MH AF Gail, MH TI Use of observational data, including surveillance studies, for evaluating AIDS therapies SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT Symposium on Statistical Issues in HIV/AIDS Research CY JUN 12-13, 1995 CL NIH, BETHESDA, MD HO NIH ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; PNEUMOCYSTIS-CARINII PNEUMONIA; PLACEBO-CONTROLLED TRIAL; UNITED-STATES; NATURAL-HISTORY; VIRUS INFECTION; HIV PREVALENCE; SAN-FRANCISCO; FUTURE-TRENDS; DOUBLE-BLIND AB This article discusses some of the limitations of observational data for assessing therapeutic effects and categorizes observational studies according to the strength of evidence. Ecologic studies based on AIDS surveillance registries have demonstrated improvements over time in median survival following the onset of AIDS, especially for patients with an initial diagnosis of Pneumocystis carinii pneumonia. Some of this improvement may be the result of secular changes in the stage of disease at diagnosis or in the completeness of detection of deaths in these cohorts, however. Other ecologic studies of the use of AZT in various subgroups strongly suggest that treatment had a favorable impact on US AIDS incidence rates in gay men in the year beginning July 1987. This article is reprinted with minor changes from Chapter 24 of AIDS Clinical Trials.(1) RP Gail, MH (reprint author), NCI,DIV CANC ETIOL,EPN 431,6130 EXECUT BLVD,MSC 7368,BETHESDA,MD 20892, USA. NR 39 TC 7 Z9 7 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 15 PY 1996 VL 15 IS 21-22 BP 2273 EP 2288 DI 10.1002/(SICI)1097-0258(19961115)15:21<2273::AID-SIM448>3.0.CO;2-3 PG 16 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA VQ193 UT WOS:A1996VQ19300003 PM 8931201 ER PT J AU Follmann, D Schoenfeld, D Williams, P AF Follmann, D Schoenfeld, D Williams, P TI Long-term follow-up in AIDS clinical trials - Discussion SO STATISTICS IN MEDICINE LA English DT Editorial Material RP Follmann, D (reprint author), NHLBI,OFF BIOSTAT RES,ROCKLEDGE CTR 2,MSC 7938,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 15 PY 1996 VL 15 IS 21-22 BP 2367 EP 2370 DI 10.1002/(SICI)1097-0258(19961115)15:21<2367::AID-SIM455>3.0.CO;2-Y PG 4 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA VQ193 UT WOS:A1996VQ19300010 ER PT J AU Albert, JM AF Albert, JM TI A control-conditional test for assessing HIV vaccine efficacy in small sample preclinical studies SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT Symposium on Statistical Issues in HIV/AIDS Research CY JUN 12-13, 1995 CL NIH, BETHESDA, MD HO NIH ID BINOMIAL PROPORTIONS; CONTINGENCY-TABLES; INFECTION AB In this paper, we discuss the analysis of data from small sample animal studies intended to evaluate HIV vaccine efficacy. The focus is on the chimpanzee model with HIV infection, a binary outcome, of primary interest. The problem becomes that of testing for a difference in independent binomial proportions, but aspects of the study design call into question the use of standard approaches. As sample sizes may be as small as one or two per group in this context, it is tempting to utilize previous data; such usage, however, carries a high price in terms of additional assumptions. We present a test, referred to as the control-conditional test, which conditions on the control data and assumes (in a manner of Bayesian estimation) only vague prior information. Comparisons are made with Fisher's exact test and an exact unconditional test. The control-conditional test is also generalized to allow the analysis of data from a differential dose design. RP Albert, JM (reprint author), NIAID,DIV AIDS,BIOSTAT RES BRANCH,6003 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 11 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 15 PY 1996 VL 15 IS 21-22 BP 2371 EP 2378 DI 10.1002/(SICI)1097-0258(19961115)15:21<2371::AID-SIM456>3.0.CO;2-B PG 8 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA VQ193 UT WOS:A1996VQ19300011 PM 8931207 ER PT J AU Rida, WN AF Rida, WN TI Assessing the effect of HIV vaccination on infectiousness SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT Symposium on Statistical Issues in HIV/AIDS Research CY JUN 12-13, 1995 CL NIH, BETHESDA, MD HO NIH ID EFFICACY; VACCINES; VIRUS; QUANTITATION; DISEASES; PLASMA AB Traditionally, measures of vaccine efficacy have focused on a vaccine's ability to prevent infection or disease. HIV vaccination, however, may have important indirect effects by reducing the level of infectiousness of vaccinees who become infected. This latter effect is not captured by the usual estimators of vaccine efficacy. To obtain an estimate of a vaccine's effect on infectiousness, Koopman and Little have proposed a trial design in which HIV-uninfected couples are randomized to the vaccine or control arm of the study. At least one member is assumed to be at risk of HIV infection from outside the partnership. Using this design, we formulate martingales from counting processes which record the number of infected participants over the course of the trial. An alternative estimator of a vaccine's effect on infectiousness along with an estimate of its variance is derived from these martingales. The precision of the estimate is shown to depend on the secondary attack rate within the couple. High secondary attack rates are required for narrow confidence intervals unless very large studies are contemplated. RP Rida, WN (reprint author), NIAID,DIV AIDS,BIOSTAT RES BRANCH,6003 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 19 TC 19 Z9 19 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 15 PY 1996 VL 15 IS 21-22 BP 2393 EP 2404 DI 10.1002/(SICI)1097-0258(19961130)15:22<2393::AID-SIM458>3.0.CO;2-W PG 12 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA VQ193 UT WOS:A1996VQ19300013 PM 8931209 ER PT J AU Kozak, CA Chakraborti, A AF Kozak, CA Chakraborti, A TI Single amino acid changes in the murine leukemia virus capsid protein gene define the target of Fv1 resistance SO VIROLOGY LA English DT Article ID LOCUS AFFECTING RESISTANCE; HOST-RANGE RESTRICTIONS; CELL-CULTURES; FV-1 TROPISM; MOUSE EMBRYO; BALB-C; DNA; MICE; INFECTION; LINES AB The mouse Fv1 genetic locus controls resistance to subgroups of ecotropic, MCF, and amphotropic murine leukemia viruses (MuLVs). In addition to the four previously defined alleles of Fv1 (Fv1(n) Fv1(b) Fv1(nr): Fv1(0)), we present evidence that the novel restriction pattern characteristic of DBA/2J mice maps to the Fv1 locus and therefore represents a novel allele, here designated Fv1(d). Previous studies had demonstrated that the Fv1-mediated viral tropism is determined within the capsid protein gene, and that N- and B-tropic virus capsids differ only in two adjacent amino acids. We introduced various amino acid substitutions al these two sites in the N-tropic AKV MLV capsid gene, and typed resulting viruses for host range on cells carrying all five Fv1 alleles as well as on cells from additional wild mouse species with Fv1-like differences in virus susceptibility. Results indicate that alteration of the first of the two amino acids does not alter tropism, but alteration of the second alone is sufficient to convert the N-tropic AKV MLV to a B-tropic virus. Substitution of leucine for arginine at this site produced a virus with an unusual tropism not characteristic of any of the naturally occurring or laboratory strains of MuLV. (C) 1996 Academic Press, Inc. RP Kozak, CA (reprint author), NIAID,MOL MICROBIOL LAB,NIH,BLDG 4,ROOM 329,BETHESDA,MD 20892, USA. NR 25 TC 129 Z9 130 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 NOV 15 PY 1996 VL 225 IS 2 BP 300 EP 305 DI 10.1006/viro.1996.0604 PG 6 WC Virology SC Virology GA VV421 UT WOS:A1996VV42100006 PM 8918916 ER PT J AU Firestone, CY Whitehead, SS Collins, PL Murphy, BR Crowe, JE AF Firestone, CY Whitehead, SS Collins, PL Murphy, BR Crowe, JE TI Nucleotide sequence analysis of the respiratory syncytial virus subgroup a cold-passaged (cp) temperature sensitive (ts) cpts-248/404 live attenuated virus vaccine candidate SO VIROLOGY LA English DT Article ID ORAL POLIOVIRUS VACCINE; 5' NONCODING REGION; GENETIC STABILITY; MESSENGER-RNA; TYPE-3 PIV3; JS STRAIN; MUTANT; TRANSCRIPTION; MUTATIONS; DELETION AB The complete nucleotide sequence of the RSV cpts-248/404 live attenuated vaccine candidate was determined from cloned cDNA and was compared to that of the RSV A2/HEK7 wild-type, cold-passaged cp-RSV, and cpts-248 virus, which constitute the series of progenitor viruses. RSV cpts-248/404 is more attenuated and more temperature sensitive (ts) (shut-off temperature 36 degrees) than its cpts-248 parent virus (shut-off temperature 38 degrees) and is currently being evaluated in phase I clinical trials in humans. Our ultimate goal is to identify the genetic basis for the host range attenuation phenotype exhibited by cp-RSV (i.e., efficient replication in tissue culture but decreased replication in chimpanzees and humans) and for the ts and attenuation phenotypes of its chemically mutagenized derivatives, cpts-248 and cpts-248/404. Compared with its cpts-248 parent, the cpts-248/404 virus possesses an amino acid change in the polymerase (L) protein and a single nucleotide substitution in the M2 gene start sequence. In total, the cpts-248/404 mutant differs from its wild-type RSV A2/HEK7 progenitor in seven amino acids [four in the polymerase (L) protein, two in the fusion (F) glycoprotein, and one in the (N) nucleoprotein] and one nucleotide difference in the M2 gene start sequence. Heterogeneity at nucleotide position 4 (G or C, negative sense, compared to G in the RSV A2/HEK7 progenitor) in the leader region of vRNA developed during passage of the cpts-248/404 in tissue culture. Biologically cloned derivatives of RSV cpts-248/404 virus that differed at position 4 possessed the same level of temperature sensitivity and exhibited the same level of replication in the upper and lower respiratory tract of mice, suggesting that heterogeneity at this position is not clinically relevant. The determination of the nucleotide sequence of the cpts-248/404 virus will allow evaluation of the stability of the eight mutations that are associated with the attenuation phenotype during vaccine production and following replication in humans. (C) 1996 Academic Press, Inc. C1 NIAID,RESP VIRUSES SECT,INFECT DIS LAB,NIH,BETHESDA,MD 20892. RI Crowe, James/B-5549-2009 OI Crowe, James/0000-0002-0049-1079 NR 25 TC 47 Z9 53 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 NOV 15 PY 1996 VL 225 IS 2 BP 419 EP 422 DI 10.1006/viro.1996.0618 PG 4 WC Virology SC Virology GA VV421 UT WOS:A1996VV42100020 PM 8918930 ER PT J AU Garboczi, DN Ghosh, P Utz, U Fan, QR Biddison, WE Wiley, DC AF Garboczi, DN Ghosh, P Utz, U Fan, QR Biddison, WE Wiley, DC TI Structure of the complex between human T-cell receptor, viral peptide and HLA-A2 SO NATURE LA English DT Article ID ANTIGEN-BINDING SITE; 3-DIMENSIONAL STRUCTURE; CRYSTAL-STRUCTURE; MHC COMPLEXES; CLASS-I; HISTOCOMPATIBILITY ANTIGEN; RECOGNITION; LYMPHOCYTES; MOLECULES; ANTIBODY AB Recognition by a T-cell antigen receptor (TCR) of peptide complexed with a major histocompatibility complex (MHC) molecule occurs through variable loops in the TCR structure which bury almost all the available peptide and a much larger area of the MHC molecule. The TCR fits diagonally across the MHC peptide-binding site in a surface feature common to all class I and class II MHC molecules, providing evidence that the nature of binding is general, A broadly applicable binding mode has implications for the mechanism of repertoire selection and the magnitude of alloreactions. C1 HARVARD UNIV,DEPT MOL & CELLULAR BIOL,CAMBRIDGE,MA 02138. HARVARD UNIV,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02138. INST RECH CLIN MONTREAL,IMMUNOL LAB,MONTREAL,PQ H2W 1R7,CANADA. NINCDS,MOL IMMUNOL SECT,NEUROIMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NR 53 TC 754 Z9 762 U1 3 U2 13 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD NOV 14 PY 1996 VL 384 IS 6605 BP 134 EP 141 DI 10.1038/384134a0 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VT336 UT WOS:A1996VT33600056 PM 8906788 ER PT J AU Trkola, A Dragic, T Arthos, J Binley, JM Olson, WC Allaway, GP ChengMayer, C Robinson, J Maddon, PJ Moore, JP AF Trkola, A Dragic, T Arthos, J Binley, JM Olson, WC Allaway, GP ChengMayer, C Robinson, J Maddon, PJ Moore, JP TI CD4-dependent, antibody-sensitive interactions between HIV-1 and its co-receptor CCR-5 SO NATURE LA English DT Article ID MONOCLONAL-ANTIBODIES; VIRUS; EXPRESSION; GP120 AB THE beta-chemokine receptor CCR-5 is an essential co-factor for fusion of HIV-1 strains of the non-syncytium-inducing (NSI) phenotype with CD4(+) T-cells(1-5). The primary binding site for human immunodeficiency virus (HIV)-1 is the CD4 molecule, and the interaction is mediated by the viral surface glycoprotein gp120 (refs 6, 7). The mechanism of CCR-5 function during HIV entry has not been defined, but we have shown previously that its beta-chemokine ligands prevent HIV-1 from fusing with the cell(1). We therefore investigated whether CCR-5 acts as a second binding site for HIV-1 simultaneously with or subsequent to the interaction between gp120 and CD4, We used a competition assay based on gp120 inhibition of the binding of the CCR-5 ligand, macrophage inflammatory protein (MIP)-1 beta, to its receptor on activated CD4(+) T cells or CCR-5-positive CD4(-) cells. We conclude that CD4 binding, although not absolutely necessary for the gp120-CCR-5 interaction, greatly increases its efficiency, Neutralizing monoclonal antibodies against several sites on gp120, including the V3 loop and CD4-induced epitopes, inhibited the interaction of gp120 with CCR-5, without affecting gp120-CD4 binding, Interference with HIV-1 binding to one or both of its receptors (CD4 and CCR-5) may be an important mechanism of virus neutralization. C1 ROCKEFELLER UNIV,AARON DIAMOND AIDS RES CTR,NEW YORK,NY 10016. NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. PROGEN PHARMACEUT INC,TARRYTOWN,NY 10591. TULANE UNIV,MED CTR,DEPT PEDIAT,NEW ORLEANS,LA 70112. RI Trkola, Alexandra/K-2115-2012 OI Trkola, Alexandra/0000-0003-1013-876X NR 20 TC 905 Z9 915 U1 5 U2 34 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD NOV 14 PY 1996 VL 384 IS 6605 BP 184 EP 187 DI 10.1038/384184a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VT336 UT WOS:A1996VT33600070 PM 8906796 ER PT J AU Landesman, SH Burns, DN Kalish, LA AF Landesman, SH Burns, DN Kalish, LA TI Prolonged rupture of membranes and transmission of the human immunodeficiency virus - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NICHHD,BETHESDA,MD 20892. NEW ENGLAND RES INST,WATERTOWN,MA 02172. RP Landesman, SH (reprint author), SUNY HLTH SCI CTR,BROOKLYN,NY 11203, USA. NR 0 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 NOV 14 PY 1996 VL 335 IS 20 BP 1533 EP 1534 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA VT340 UT WOS:A1996VT34000018 ER PT J AU Ambrosone, CB Freudenheim, JL Graham, S Marshall, JR Vena, JE Brasure, JR Michalek, AM Laughlin, R Nemoto, T Gillenwater, KA Harrington, AM Shields, PG AF Ambrosone, CB Freudenheim, JL Graham, S Marshall, JR Vena, JE Brasure, JR Michalek, AM Laughlin, R Nemoto, T Gillenwater, KA Harrington, AM Shields, PG TI Cigarette smoking, N-acetyltransferase 2 genetic polymorphisms, and breast cancer risk SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RAT MAMMARY-GLAND; METABOLIC-ACTIVATION; ALCOHOL-CONSUMPTION; COLORECTAL-CANCER; BLADDER-CANCER; ACETYLATOR POLYMORPHISM; EPITHELIAL-CELLS; DNA ADDUCTS; PHENOTYPE; WOMEN AB Objective.-To determine if N-acetyltransferase 2 (NAT2) polymorphisms result in decreased capacity to detoxify carcinogenic aromatic amines in cigarette smoke, thus making some women who smoke more susceptible to breast cancer. Design.-Case-control study with genetic analyses, DNA analyses were performed for 3 polymorphisms accounting for 90% to 95% of the slow acetylation phenotype among whites. Setting and Participants.-White women with incident primary breast cancer (n=304) and community controls (n=327). Results.-Neither smoking nor NAT2 status was independently associated with breast cancer risk. There were no clear patterns of increased risk associated with smoking by NAT2 status among premenopausal women. In postmenopausal women, NAT2 strongly modified the association of smoking with risk. For slow acetylators, current smoking and smoking in the distant past increased breast cancer risk in a dose-dependent manner (odds ratios [95% confidence intervals] for the highest quartile of cigarettes smoked 2 and 20 years previously, 4.4 [1.3-14.8] and 3.9 [1.4-10.8], respectively). Among rapid acetylators, smoking was not associated with increased breast cancer risk. Conclusions.-Our results suggest that smoking may be an important risk factor for breast cancer among postmenopausal women who are slow acetylators, demonstrate heterogeneity in response to carcinogenic exposures, and may explain previous inconsistent findings for cigarette smoking as a breast cancer risk factor. C1 SUNY BUFFALO,DEPT SOCIAL & PREVENT MED,BUFFALO,NY 14260. SUNY BUFFALO,DEPT SURG,BUFFALO,NY 14260. NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. RP Ambrosone, CB (reprint author), NATL CTR TOXICOL RES,DIV MOL EPIDEMIOL,3900 NCTR RD,JEFFERSON,AR 72079, USA. RI Shields, Peter/I-1644-2012 FU NCI NIH HHS [CA-01633, CA-11535, CA-62995] NR 77 TC 279 Z9 282 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 13 PY 1996 VL 276 IS 18 BP 1494 EP 1501 DI 10.1001/jama.276.18.1494 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA VQ774 UT WOS:A1996VQ77400032 PM 8903261 ER PT J AU Delporte, C Chen, ZJ Baum, BJ AF Delporte, C Chen, ZJ Baum, BJ TI Aquaporin 1 expression during the cell cycle in A5 cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID INTEGRAL MEMBRANE-PROTEIN; DNA-REPLICATION; WATER CHANNELS; GROWTH; CHIP; FAMILY AB Aquaporin 1 is an integral membrane protein which functions as a water channel. It is reportedly (Lanahan et al., 1992) encoded by a delayed early reponse gene. We asked if the expression of aquaporin 1 varied during the cell cycle in an epithelial cell line (A5) in which its is constitutively expressed. A5 cells were synchronized by double thymidine block and cell cycle stages defined by flow cytometric analysis. AQP1 mRNA and protein levels were highest when most cells were in G(0)/G(1), then decreased similar to 40-60% when the cells moved into the S and G(2)/M phases. These results provide the first demonstration that constitutive aquaporin 1 expression can fluctuate during the cell cycle. (C) 1996 Academic Press, Inc. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,NIH,BETHESDA,MD 20892. NIDR,ORAL MED LAB,NIH,BETHESDA,MD 20892. NR 18 TC 17 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 12 PY 1996 VL 228 IS 2 BP 223 EP 228 DI 10.1006/bbrc.1996.1645 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VT768 UT WOS:A1996VT76800001 PM 8920898 ER PT J AU Owman, C Blay, P Nilsson, C Lolait, SJ AF Owman, C Blay, P Nilsson, C Lolait, SJ TI Cloning of human cDNA encoding a novel heptahelix receptor expressed in Burkitt's lymphoma and widely distributed in brain and peripheral tissues SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROTEIN-COUPLED RECEPTOR; CHEMOKINE RECEPTOR; MOLECULAR-CLONING; DIFFERENTIATION; ACTIVATION; BLR1 AB Using PCR with degenerate primers and screening of a human B-cell lymphoblast cDNA library, a full-length cDNA encoding a 375-amino-acid protein was isolated. It contains seven regions of hydrophobic amino acids probably representing membrane-spanning domains of a novel heptahelix receptor, tentatively named CMKRL2. It shows nearly 30% overall identity with the high-affinity IL8 receptor and similar degree of homology with other chemoattractant receptors, including the ''fusin'' coreceptors for HIV1. Measurements of various transduction pathways following application of a panel of chemokines to transfected cells failed to evoke any reproducible response. Although the natural ligand for CMKRL2 could, thus, not be identified, receptor expression in spleen and lymph nodes as well as in Burkitt's lymphoma (irrespective of EBV status) supports a functional role in activated B-cells. Receptor message was ubiquitously distributed in normal peripheral tissues and CNS, suggesting that CMKRL2 is expressed in widespread cell populations, such as macrophages and neuroglia. (C) 1996 Academic Press, Inc. C1 NIMH,CELL BIOL LAB,NIH,BETHESDA,MD 20892. RP Owman, C (reprint author), LUND UNIV,WALLENBERG NEUROSCI CTR,DEPT PHYSIOL & NEUROSCI,MOL NEUROBIOL SECT,LUND,SWEDEN. NR 26 TC 112 Z9 134 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 12 PY 1996 VL 228 IS 2 BP 285 EP 292 DI 10.1006/bbrc.1996.1654 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VT768 UT WOS:A1996VT76800010 PM 8920907 ER PT J AU Derua, R Gustafson, KR Pannell, LK AF Derua, R Gustafson, KR Pannell, LK TI Analysis of the disulfide linkage pattern in circulin A and B, HIV-inhibitory macrocyclic peptides SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROTEIN; SAPECIN; SECTOR; ARRAY AB Circulin A and B are members of a family of macrocyclic peptides, originally isolated from the tropical tree Chassalia parvifolia, that have been shown to display anti-HIV activity. Complete structural elucidation of these highly constrained peptides was difficult due to their cyclic amide backbone and the presence of six disulfide-linked cysteines. in the present study, the disulfide pairing motif of circulin A and circulin B was determined. Since the circulins were resistant to enzymatic proteolysis, cysteine residue pairings were identified by analysis of the complex mixture of cleavage products that resulted from partial acid hydrolysis of the native peptides. Combined utilization of HPLC, fast atom bombardment mass spectrometry and peptide recognition software(''F-MASS'' and ''F-LINK'' programs) were employed to identify the cleavage products. Thus, we were able to unambiguously identify the disulfide linkage pattern in circulin A and circulin B as Cys(1)-Cys(4), Cys(2)-Cys(5) and Cys(3)-Cys(6) where the numbers on the cystine residues refer to their respective order in the peptides. (C) 1996 Academic Press, Inc. C1 NIDDK,NIH,ANALYT CHEM LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,LDDRD,FREDERICK,MD 21702. NR 15 TC 41 Z9 45 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 12 PY 1996 VL 228 IS 2 BP 632 EP 638 DI 10.1006/bbrc.1996.1708 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VT768 UT WOS:A1996VT76800064 PM 8920961 ER PT J AU Han, Y Chaudhary, AG Chordia, MD Sackett, DL PerezRamirez, B Kingston, DGI Bane, S AF Han, Y Chaudhary, AG Chordia, MD Sackett, DL PerezRamirez, B Kingston, DGI Bane, S TI Interaction of a fluorescent derivative of paclitaxel (Taxol) with microtubules and tubulin-colchicine SO BIOCHEMISTRY LA English DT Article ID CALF BRAIN TUBULIN; SELF-ASSOCIATION; BETA-TUBULIN; BIOLOGICAL EVALUATION; BINDING-SITE; AMINO-ACIDS; ANALOGS; STOICHIOMETRY; CONFORMATIONS; DISSOCIATION AB A fluorescent derivative of paclitaxel, 2-debenzoyl-2-(m-aminobenzoyl)paclitaxel (2-AB-PT), has been prepared. 2-AB-PT induces microtubule assembly in vitro, but is about 3-fold less potent than paclitaxel itself. The absorption and emission characteristics of 2-AB-PT were analyzed as a function of solvent. It was found that both spectra were perturbed by specific solvent effects when the solvent contained a hydrogen bond donor. The absorption and fluorescence spectra of 2-AB-PT bound to microtubules could not be mimicked by a single solvent, but the absorption and emission maxima of the tubulin-bound species could be duplicated by a solvent mixture of DMSO and water. These results indicate that the fluorophore binding site on the microtubule is in an environment of intermediate polarity that is accessible to a hydrogen bond donor in the vicinity of the m-amino group, In addition, tubulin fluorescence is quenched in the 2-AB-PT/microtubule complex, and energy transfer from tubulin to 2-AB-PT is apparent. These results indicate that substituents on the C-2 position of paclitaxel associate with tubulin when bound to the microtubule. 2-AB-PT binding to microtubules was quantitatively analyzed by fluorescence titrations, Two classes of binding sites for 2-AB-PT on microtubules were found. The high affinity site has an apparent association constant (K-1app) Of 2.0 (+/-0.9) x 10(7) M(-1) and an apparent binding stoichiometry (n(lapp)) of 0.8 (+/-0.1) sites/tubulin dimer in the microtubule, The apparent association constant for the lower affinity site is about 100-fold less than that of the higher affinity site (K-2app= 2.1 (+/-0.7) x 10(5) M(-1)), and the stoichiometry of the lower affinity site or class of sites (n(2app)) was found to be 1.3 +/- 0.1. Paclitaxel blocked 2-AB-PT binding to the high affinity site, No binding of 2-AB-PT to unassembled tubulin was observed, but the emission spectrum of 2-AB-PT in the presence of the tubulin-colchicine complex resembled the emission spectrum of the ligand bound to microtubules. It was previously shown that paclitaxel can induce GTPase activity in the tubulin-colchicine complex, indicating that paclitaxel can bind to unassembled tubulin in its complex with colchicine [Carlier, M.-F., & Pantaloni, D. (1983) Biochemistry 22, 4814-4822]. Rigorous characterization of the aggregation state of the protein under these conditions demonstrates that 2-AB-PT is also capable of binding to the tubulin-colchicine complex. C1 SUNY BINGHAMTON,DEPT CHEM,BINGHAMTON,NY 13902. VIRGINIA POLYTECH INST & STATE UNIV,DEPT CHEM,BLACKSBURG,VA 24061. NIDDK,NIH,BIOCHEM PHARMACOL LAB,BETHESDA,MD 20892. BRANDEIS UNIV,GRAD DEPT BIOCHEM,WALTHAM,MA 02254. RI Chordia, Mahendra/A-4706-2008; Bane, Susan/C-1414-2013; OI Bane, Susan/0000-0002-4270-6314; Kingston, David/0000-0001-8944-246X FU NCI NIH HHS [CA48974, CA55131] NR 47 TC 39 Z9 39 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 12 PY 1996 VL 35 IS 45 BP 14173 EP 14183 DI 10.1021/bi960774l PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VT081 UT WOS:A1996VT08100017 PM 8916903 ER PT J AU Jui, HY Accili, D Taylor, SI AF Jui, HY Accili, D Taylor, SI TI Characterization of a hybrid receptor formed by dimerization of the insulin receptor-related receptor (IRR) with the insulin receptor (IR): Coexpression of cDNAs encoding human IRR and human IR in NIH-3T3 cells SO BIOCHEMISTRY LA English DT Article ID GROWTH-FACTOR-I; LIGAND; AUTOPHOSPHORYLATION; HETEROGENEITY; PATIENT; COMPLEX; FAMILY AB In many tissues, the insulin receptor-related receptor (IRR) is colocalized with the homologous receptors for insulin and insulin-like growth factor-I (IGF-I). Since a ligand for the IRR has not yet been identified, it has been proposed previously that IRR may be activated and transduce its signal via formation of hybrids with the insulin and IGF-I receptors. To test this hypothesis, we have coexpressed the human IRR and the human insulin receptor (IR) in NIH-3T3 cells. Although IRR/IR hybrid receptors were detected in these cells by using immunoprecipitation techniques, only a small proportion of each receptor was assembled into hybrids. While insulin was capable of stimulating insulin receptor autophosphorylation in these cells, there was no detectable increase in the total phosphotyrosine content of IRR, We conclude that the IRR/IR hybrid receptor does not play a major role in IRR signal transduction in response to insulin in NIH-3T3-hIRR/hIR cells. C1 NIDDKD,DIABET BRANCH,NIH,BETHESDA,MD 20892. NR 23 TC 10 Z9 11 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 12 PY 1996 VL 35 IS 45 BP 14326 EP 14330 DI 10.1021/bi9613032 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VT081 UT WOS:A1996VT08100033 PM 8916919 ER PT J AU Freeman, L Kurumizaka, H Wolffe, AP AF Freeman, L Kurumizaka, H Wolffe, AP TI Functional domains for assembly of histones H3 and H4 into the chromatin of Xenopus embryos SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SILENT MATING LOCI; DNA-REPLICATION INVITRO; NUCLEOSOMAL DNA; N-TERMINUS; YEAST; ACETYLATION; REPRESSION; OCTAMER; LAEVIS; IDENTIFICATION AB Histones H3 and H4 have a well defined structural role in the nucleosome and an established role in the regulation of transcription. We have made use of a microinjection strategy using Xenopus embryos to define the minimal structural components of H3 and H4 necessary for nucleosome assembly into metazoan chromosomes in vivo. we find that both the N-terminal tail of H4, including all sites of acetylation, and the C-terminal alpha-helix of the H4 histone fold domain are dispensable for chromatin assembly. The N-terminal tail and an N-terminal alpha-helix of H3 are also dispensable for chromatin assembly. However, the remainder of the H3 and H4 histone folds are essential for incorporation of these proteins into chromatin. We suggest that elements of the histone fold domain maintain both nucleosomal integrity and have distinct functions essential for cell viability. C1 NICHHD,NIH,MOL EMBRYOL LAB,BETHESDA,MD 20892. NR 40 TC 34 Z9 34 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 12 PY 1996 VL 93 IS 23 BP 12780 EP 12785 DI 10.1073/pnas.93.23.12780 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VT054 UT WOS:A1996VT05400022 PM 8917496 ER PT J AU Yuan, Y Barry, CE AF Yuan, Y Barry, CE TI A common mechanism for the biosynthesis of methoxy and cyclopropyl mycolic acids in Mycobacterium tuberculosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE methyl transferase; mycolic acids; tuberculosis; cation; cyclopropane synthase ID CELL-WALL; IDENTIFICATION; FARCINOGENES; SENEGALENSE; FORTUITUM; SMEGMATIS; CHELONAE; PATTERNS AB Mycobacterium tuberculosis produces three classes of mycolic acids that differ primarily in the presence and nature of oxygen-containing substituents in the distal portion of the meromycolate branch. The methoxymycolate series has a methoxy group adjacent to a methyl branch, in addition to a cyclopropane in the proximal position. Using the gene for the enzyme that introduces the distal cyclopropane (cma1) as a probe, we have cloned and sequenced a cluster of genes coding for four highly homologous methyl transferases (mma1-4). When introduced into Mycobacterium smegmatis, this gene cluster conferred the ability to synthesize methoxymycolates. By determining the structure of the mycolic acids produced following expression of each of these genes individually and in combination, we have elucidated the biosynthetic steps responsible for the production of the major series of methoxymycolates. The mma4 gene product (MMAS-4) catalyzes an unusual S-adenosyl-L-methionine-dependent transformation of the distal cis-olefin into a secondary alcohol with an adjacent methyl branch. MMAS-3 O-methylates this secondary alcohol to form the corresponding methyl ether, and MMAS-2 introduces a cis-cyclopropane in the proximal position of the methoxy series. The similarity of these reactions and the enzymes that catalyze them suggests that some of the structural diversity of mycolic acids results from different chemical fates of a common cationic intermediate, which in turn results from methyl group addition to an olefinic mycolate precursor. C1 NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,TB RES UNIT,HAMILTON,ON 59840,CANADA. RI Barry, III, Clifton/H-3839-2012 FU Intramural NIH HHS [Z01 AI000783-11] NR 32 TC 99 Z9 107 U1 4 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 12 PY 1996 VL 93 IS 23 BP 12828 EP 12833 DI 10.1073/pnas.93.23.12828 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VT054 UT WOS:A1996VT05400030 PM 8917504 ER PT J AU Morinaga, N Tsai, SC Moss, J Vaughan, M AF Morinaga, N Tsai, SC Moss, J Vaughan, M TI Isolation of a brefeldin A-inhibited guanine nucleotide-exchange protein for ADP ribosylation factor (ARF) 1 and ARF3 that contains a Sec7-like domain SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID YEAST GOLGI-APPARATUS; SACCHAROMYCES-CEREVISIAE; CHOLERA-TOXIN; BOVINE BRAIN; TRANSPORT; SEC7; CELL; COMPONENTS; ENCODES; GTP AB Brefeldin A (BFA) inhibited the exchange of ADP ribosylation factor (ARF)-bound GDP for GTP by a Golgi-associated guanine nucleotide-exchange protein (GEP) [Helms, J. B. & Rothman, J. E. (1992) Nature (London) 360, 352-354; Donaldson, J. G., Finazzi, D. & Klausner, R.D. (1992) Nature (London) 360, 350-352]. Cytosolic ARF GEP was also inhibited by BFA, but after purification from bovine brain and rat spleen, it was no longer BFA-sensitive [Tsai, S.-C., Adamik, R., Moss, J. & Vaughan, M. (1996) Proc. Natl. Acad. Sci. USA 93, 305-309]. We describe here purification from bovine brain cytosol of a BFA-inhibited GEP, After chromatography on DEAE-Sephacel, hydroxylapatite, and Mono Q and precipitation at pH 5.8, GEP was eluted from Superose 6 as a large molecular weight complex at the position of thyroglobulin (approximate to 670 kDa). After SDS/PAGE of samples from column fractions, silver-stained protein bands of approximate to 190 and 200 kDa correlated with activity, BFA-inhibited GEP activity of the 200-kDa protein was demonstrated following electroelution from the gel and renaturation by dialysis, Four tryptic peptides from the 200-kDa protein had amino acid sequences that were 47% identical to sequences in Sec7 from Saccharomyces cerevisiae (total of 51 amino acids), consistent with the view that the BFA-sensitive 200-kDa protein may be a mammalian counterpart of Sec7 that plays a similar role in cellular vesicular transport and Sec7 may be a GEP for one or more yeast ARFs. RP Morinaga, N (reprint author), NHLBI,PRIMARY CRIT CARE MED BRANCH,BETHESDA,MD 20892, USA. NR 20 TC 115 Z9 116 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 12 PY 1996 VL 93 IS 23 BP 12856 EP 12860 DI 10.1073/pnas.93.23.12856 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VT054 UT WOS:A1996VT05400035 PM 8917509 ER PT J AU Sackett, DL Saroff, HA AF Sackett, DL Saroff, HA TI The multiple origins of cooperativity in binding to multi-site lattices SO FEBS LETTERS LA English DT Review ID PROTEIN; MICROTUBULES; EQUILIBRIUM; LIGANDS AB Binding events involving the reversible association of ligands with polymeric lattices of binding sites are common in biology and frequently exhibit significant cooperativity in binding. Positive and negative cooperativity in binding may be detected by characteristic changes in binding curves for multiple binding, compared to the binding expected for simple, independent binding events that are based on combinatorial considerations only. Cooperativity arises from ligand-dependent interactions distinct from binding per se. Ligand-dependent nearest neighbor interactions may be of two types referred to as ligand-lattice (which can only occur if a bound ligand is unneighbored) and ligand-ligand (which can occur if two or more bound ligands are adjacent). The molecular mechanisms underlying these two sources of cooperativity are not the same. Identical cooperative binding curves may be produced by changes from unity in parameters representing either one or both of these interaction types. Positive cooperativity mag equally result from destabilizing ligand-lattice interactions that disfavor initial, unneighbored binding, stabilizing ligand-ligand interactions that favor subsequent, neighbored binding, or both. The structural origins of these are different, and cooperativity may emerge from multiple structural interactions. C1 NIDDK,BIOCHEM PHARMACOL LAB,NIH,BETHESDA,MD 20892. RP Sackett, DL (reprint author), NCI,MED BRANCH,NIH,BLDG 8,ROOM 2A-23,8 CTR DR,MSC 0830,BETHESDA,MD 20892, USA. NR 19 TC 17 Z9 17 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 11 PY 1996 VL 397 IS 1 BP 1 EP 6 DI 10.1016/S0014-5793(96)01020-4 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA VT536 UT WOS:A1996VT53600001 PM 8941702 ER PT J AU Natarajan, AT Boei, JJWA Vermeulen, S Balajee, AS AF Natarajan, AT Boei, JJWA Vermeulen, S Balajee, AS TI Frequencies of X-ray induced pericentric inversions and centric rings in human blood lymphocytes detected by FISH using chromosome arm specific DNA libraries SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE pericentric inversion; arm specific probe; FISH ID INSITU HYBRIDIZATION; CYTOGENETIC ANALYSIS; RADIATION AB Frequencies of intra-chromosomal exchanges (pericentric inversions and centric rings) and inter-chromosomal exchanges (dicentrics and translocations) in X-irradiated (2.5 Gy) human lymphocytes have been estimated. To detect these events we employed FISH (fluorescence in situ hybridization) technique and arm specific painting probes for chromosomes #1 and #3. The ratio between centric rings and pericentric inversions was found to be about 1. For intra-changes to inter-changes, the ratio (F) was between 6 and 9. Based on the total number of colour junctions involving chromosomes #1 and #3 it was found that exchanges between the arms of the same chromosome occur about 8.7 times more than inter-chromosomal exchanges calculated on the basis of the DNA content of the chromosomes and random induction of aberrations in the total genome. Chromosomal organization in interphase nucleus appears to promote the formation of more intra-changes than inter-changes following X-irradiation, most probably due to close proximity of the two arms of a chromosome. C1 JA COHEN INTER UNIV,INST RADIAT PROTECT & RADIOPATHOL,LEIDEN,NETHERLANDS. NIH,MOL GENET LAB,CTR GERONTOL RES,BALTIMORE,MD 21224. RP Natarajan, AT (reprint author), LEIDEN UNIV,DEPT RADIAT GENET & CHEM MUTAGENESIS,WASSENAARSEWEG 72,NL-2333 AL LEIDEN,NETHERLANDS. NR 18 TC 32 Z9 32 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD NOV 11 PY 1996 VL 372 IS 1 BP 1 EP 7 DI 10.1016/S0027-5107(96)00209-6 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA WE201 UT WOS:A1996WE20100001 PM 9003525 ER PT J AU Bryngerson, JD Thirumalai, D AF Bryngerson, JD Thirumalai, D TI Internal constraints induce localization in an isolated polymer molecule - Reply SO PHYSICAL REVIEW LETTERS LA English DT Editorial Material C1 UNIV MARYLAND,INST PHYS SCI & TECHNOL,COLLEGE PK,MD 20742. RP Bryngerson, JD (reprint author), NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD NOV 11 PY 1996 VL 77 IS 20 BP 4277 EP 4277 DI 10.1103/PhysRevLett.77.4277 PG 1 WC Physics, Multidisciplinary SC Physics GA VR556 UT WOS:A1996VR55600046 ER PT J AU Noel, T Nicolas, JL Boulo, V Mialhe, E Roch, P AF Noel, T Nicolas, JL Boulo, V Mialhe, E Roch, P TI Development of a colony-blot ELISA assay using monoclonal antibodies to identify Vibrio P1 responsible for ''brown ring disease'': In the clam Tapes philippinarum SO AQUACULTURE LA English DT Article DE Tapes philippinarum; brown ring disease; Vibrio P1 ID BONAMIA-OSTREAE ASCETOSPORA; EDULIS MOLLUSCA; BIVALVIA; DIAGNOSIS AB Since 1987, brown ring disease has caused mass mortalities on various cultured clam-beds. The causal agent is a Vibrio sp. called Vibrio P1. The problem is to perform a suitable, reliable, rapid and sensitive technique to detect this bacterium in the environment. Therefore, monoclonal antibodies (mAb) were prepared according to hybridoma technology. One mAb was selected by enzyme-linked immunosorbent assay (ELISA) because of its capacity to react specifically with V. P1. Nitro-cellulose membrane immunoassay (colony-blot ELISA) was developed to detect directly V P1 in samples, Results of identification of 223 bacteria by the biochemical method and by the colony-blot ELISA method were compared. The specificity and the sensitivity were 100% in both cases. Our results indicate that the colony-blot ELISA is sensitive, easy to perform and is especially suited for routine diagnostic work. C1 IFREMER,LAB RECH AQUACOLES,F-29280 PLOUZANE,FRANCE. NIH,LAB PARASITE DIS,BETHESDA,MD 20892. RP Noel, T (reprint author), UNIV MONTPELLIER 2,CNRS,IFREMER,2 PL E BATAILLON,CASE COURRIER 80,F-34095 MONTPELLIER 5,FRANCE. NR 24 TC 9 Z9 9 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0044-8486 J9 AQUACULTURE JI Aquaculture PD NOV 10 PY 1996 VL 146 IS 3-4 BP 171 EP 178 DI 10.1016/S0044-8486(96)01385-3 PG 8 WC Fisheries; Marine & Freshwater Biology SC Fisheries; Marine & Freshwater Biology GA VZ851 UT WOS:A1996VZ85100002 ER PT J AU Aran, JM Licht, T Gottesman, MM Pastan, I AF Aran, JM Licht, T Gottesman, MM Pastan, I TI Complete restoration of glucocerebrosidase deficiency in Gaucher fibroblasts using a bicistronic MDR retrovirus and a new selection strategy SO HUMAN GENE THERAPY LA English DT Article ID MEDIATED GENE-TRANSFER; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; CELL-LINES; MONOCLONAL-ANTIBODIES; DRUG; DISEASE; EXPRESSION; VECTORS; THERAPY AB Retrovirus-mediated gene transfer is currently the most common method for the application of genetic therapy to cancer and many inherited and acquired disorders. Here we report the generation of an amphotropic producer cell line (CA2) that synthesizes viral particles carrying a bicistronic cassette in which the selectable MDR1 cDNA encoding P-glycoprotein (P-gp) a multidrug efflux pump, and the human glucocerebrosidase (GC) gene are transcriptionally fused. Transduction of human Gaucher fibroblasts with this recombinant virus allowed coordinate expression of P-gp and GC. Treatment of the transduced fibroblasts with various cytotoxic substrates of P-gp selected for cells with increased expression of GC, which paralleled the stringency of drug selection. Thus, selection of the genetically modified Gaucher fibroblasts in 1 mu g/ml colchicine raised their GC activity levels from nearly undetectable to those present in WI-38 normal human fibroblasts, correcting the enzyme deficiency present in Gaucher cells. Moreover, by simultaneously inhibiting the P-gp pump, it was possible to use much lower concentrations of colchicine to select for high-level expression of MDR1 and GC. Thus, selection with colchicine at 5 ng/ml in combination with the P-gp inhibitors verapamil or PSC 833 produced a complete correction of the GC deficiency hi the CA2-transduced fibroblasts. These combination regimens, already in clinical use for the treatment of multidrug-resistant malignancies, may prove useful in gene therapy trials when utilized for high level selection of a nonselectable gene such as glucocerebrosidase when transcriptionally fused to the MDR1 gene. C1 NCI,MOL BIOL LAB,DIV BASIC SCI,BETHESDA,MD 20892. NCI,CELL BIOL LAB,DIV BASIC SCI,BETHESDA,MD 20892. NR 47 TC 22 Z9 22 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV 10 PY 1996 VL 7 IS 17 BP 2165 EP 2175 DI 10.1089/hum.1996.7.17-2165 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WD328 UT WOS:A1996WD32800011 PM 8934230 ER PT J AU Kagami, H OConnell, BC Baum, BJ AF Kagami, H OConnell, BC Baum, BJ TI Evidence for the systemic delivery of a transgene product from salivary glands SO HUMAN GENE THERAPY LA English DT Article ID HUMAN FACTOR-IX; ADENOVIRUS-MEDIATED TRANSFER; GENE-THERAPY; HEMOPHILIA-B; CFTR CDNA; RAT; EXPRESSION; CELLS; ALPHA-1-ANTITRYPSIN; HEPATOCYTES AB The aim of this study was to assess the feasibility of using gene transfer to salivary glands to direct the systemic delivery of therapeutic proteins in vivo. We used a replication-deficient recombinant adenovirus vector (Ad alpha 1AT) that encodes human alpha 1-antitrypsin (h alpha 1-AT), which we used as a marker protein. Ad alpha 1AT (5 x 10(9) pfu) was administered by retrograde ductal instillation to the submandibular glands of male rats. The amount of hal-AT found in the salivary glands, saliva, serum, and other tissues was analyzed by a sensitive enzyme-linked immunosorbent assay (ELISA). Maximal levels of the marker protein were detected at 24-48 hr post-virus administration for glands (274 ng/mg protein), saliva (similar to 313 ng/ml), and serum (similar to 5 ng/ml). Serum levels remained elevated for 96 hr, whereas the measured half-life for the marker protein was similar to 2 hr. Generally little to no h alpha 1-AT was detectable in most other organs, However, we were able to measure low levels of marker protein in tissues immediately surrounding infected glands. In all animals studied, levels of h alpha 1-AT were higher in the glandular venous effluent than in arterial blood, Similar results were found with parotid glands. The aggregate data demonstrate that salivary glands may be a target for the nonsurgical, systemic delivery of transgene-encoded therapeutic proteins for diseases that require relatively low circulating protein levels. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. OI O'Connell, Brian/0000-0003-4529-7664 NR 30 TC 69 Z9 69 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV 10 PY 1996 VL 7 IS 17 BP 2177 EP 2184 DI 10.1089/hum.1996.7.17-2177 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WD328 UT WOS:A1996WD32800012 PM 8934231 ER PT J AU Schneerson, R Robbins, JB Taranger, J Lagergard, T Trollfors, B AF Schneerson, R Robbins, JB Taranger, J Lagergard, T Trollfors, B TI A toxoid vaccine for pertussis as well as diphtheria? Lessons to be relearned SO LANCET LA English DT Editorial Material ID WHOOPING-COUGH; FILAMENTOUS HEMAGGLUTININ; EFFICACY; TOXIN; ANTIBODIES; INFECTION; CHILDREN; TRIAL C1 GOTHENBURG UNIV,DEPT PAEDIAT,GOTHENBURG,SWEDEN. GOTHENBURG UNIV,DEPT MED MICROBIOL & IMMUNOL,GOTHENBURG,SWEDEN. RP Schneerson, R (reprint author), NICHHD,DEV & MOL IMMUN LAB,NIH,ROOM 424,BLDG 6,BETHESDA,MD 20892, USA. NR 40 TC 43 Z9 43 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD NOV 9 PY 1996 VL 348 IS 9037 BP 1289 EP 1292 DI 10.1016/S0140-6736(96)05243-9 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA VR555 UT WOS:A1996VR55500014 PM 8909384 ER PT J AU Krogstad, DJ Pearson, RD Bennett, JE Dolin, R Mandell, GL AF Krogstad, DJ Pearson, RD Bennett, JE Dolin, R Mandell, GL TI Dosage for malaria treatment SO LANCET LA English DT Letter C1 UNIV VIRGINIA,HLTH SCI CTR,CHARLOTTESVILLE,VA. NIAID,CLIN INVEST LAB,NIH,BETHESDA,MD 20892. UNIV ROCHESTER,SCH MED & DENT,DEPT MED,ROCHESTER,NY 14642. RP Krogstad, DJ (reprint author), TULANE UNIV,SCH PUBL HLTH & TROP MED,DEPT TROP MED,NEW ORLEANS,LA 70112, USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD NOV 9 PY 1996 VL 348 IS 9037 BP 1311 EP 1311 DI 10.1016/S0140-6736(05)65787-X PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VR555 UT WOS:A1996VR55500046 PM 8909393 ER PT J AU Schrenk, D Michalke, A Gant, TW Brown, PC Silverman, JA Thorgeirsson, SS AF Schrenk, D Michalke, A Gant, TW Brown, PC Silverman, JA Thorgeirsson, SS TI Multidrug resistance gene expression in rodents and rodent hepatocytes treated with mitoxantrone SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE extrahepatic organs; hepatocytes; induction; mitoxantrone; multidrug resistance; rodent liver ID P-GLYCOPROTEIN; RAT-LIVER; TRANSCRIPTIONAL REPRESSOR; MESSENGER-RNA; CELLS; FAMILY; INDUCTION; MOUSE; DRUGS; 2-ACETYLAMINOFLUORENE AB Overexpression of P-glycoprotein in tumor cells can represent a severe drawback for cancer chemotherapy. P-glycoprotein acts as an efflux transporter for a variety of chemotherapeutic agents. It is encoded by multidrug resistance (mdr) genes of the subfamily 1 in humans (MDR1) and rodents (mdr1a and 1b). Because mdr1 gene expression is inducible in cultured rat hepatocytes and in rat liver with chemical carcinogens such as 2-acetyiaminofluorene or aflatoxin B-1, which form DNA-binding electrophiles during their metabolism, we investigated whether the DNA-damaging chemotherapeutic drug mitoxantrone may induce multidrug resistance in rodents and in hepatocytes in primary culture. In H4IIE rat hepatoma cells stably transfected with a luciferase construct containing the rat mdr1b promoter, mitoxantrone caused a concentration-dependent increase in promoter activity. Mdr1 gene expression in cultured rat hepatocytes was enhanced at mitoxantrone concentrations greater than or equal to 0.1 mu M and in mouse hepatocytes at 5 mu M. In hepatocytes from both species, a correlation was found between mdr1 induction and the inhibition of protein synthesis. In vivo, mitoxantrone was a very powerful inducer of mdr1 gene expression in rat liver and small intestine. In rat kidney, induction of mRNA was lower, and a marginal effect was seen in lung. In contrast with rats, no significant induction of mdr1 gene expression was obtained in mouse liver. Probably as a consequence of inhibition of protein synthesis, mitoxantrone did not lead to a pronounced elevation of P-glycoprotein levels in rat liver and kidney. Copyright (C) 1996 Elsevier Science Inc. C1 UNIV LEICESTER,MRC,TOXICOL UNIT,LEICESTER LE1 9HN,LEICS,ENGLAND. NCI,EXPT CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. RP Schrenk, D (reprint author), UNIV TUBINGEN,INST TOXICOL,WILHELMSTR 56,D-72074 TUBINGEN,GERMANY. NR 46 TC 21 Z9 21 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD NOV 8 PY 1996 VL 52 IS 9 BP 1453 EP 1460 DI 10.1016/S0006-2952(96)00512-6 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VP549 UT WOS:A1996VP54900017 PM 8937457 ER PT J AU Rondinone, CM Zarnowski, MJ Londos, C Smith, UPG AF Rondinone, CM Zarnowski, MJ Londos, C Smith, UPG TI The inhibitory effect of staurosporine on insulin action is prevented by okadaic acid. Evidence for an important role of serine/threonine phosphorylation in eliciting insulin-like effects SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE staurosporine; insulin inhibition; serine/threonine phosphorylation; okadaic acid ID KINASE-C ACTIVITY; PROTEIN-KINASE; RAT ADIPOCYTES; TRANSLOCATION; STIMULATION; RECEPTOR; 3-KINASE; REQUIREMENT; ACTIVATION; WORTMANNIN AB The serine/threonine phosphatase inhibitor, okadaic acid (OA), exerted several insulin-like effects in rat adipose cells and was, in part, synergistic with insulin. OA stimulated glucose transport activity, altered the electrophoretic mobility of IRS-1, increased the phosphorylation of the MAP-kinases ERK 1 and 2 on tyrosine sites, markedly increased MAP kinase activity and also acted synergistically with insulin in activating these enzymes. However, OA did not increase PI 3-kinase activity or the tyrosine phosphorylation of key upstream proteins in insulin's signaling cascade. Staurosporine virtually completely inhibited the insulin-stimulated glucose transport and MAP kinase activation in spite of a maintained high PI 3-kinase activity. In contrast, the effects of OA alone or in the presence of insulin were less, or not at all, affected. These data suggest that OA exerts an insulin-like effect through a serine/threonine-related pathway which is distinct from, but converges with, that of insulin downstream PI 3-kinase and upon which staurosporine exerts an inhibitory effect. C1 GOTHENBURG UNIV,SAHLGRENS HOSP,DEPT INTERNAL MED,LUNDBERG LAB DIABET RES,S-41345 GOTHENBURG,SWEDEN. NIDDKD,CELLULAR & DEV BIOL LAB,NIH,BETHESDA,MD 20892. NIDDKD,SECT EXPT DIABET,NIH,BETHESDA,MD 20892. NR 24 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD NOV 8 PY 1996 VL 1314 IS 1-2 BP 49 EP 56 DI 10.1016/S0167-4889(96)00075-4 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VW035 UT WOS:A1996VW03500007 PM 8972717 ER PT J AU Grigoryev, S Stewart, AE Kwon, YT Arfin, SM Bradshaw, RA Jenkins, NA Copeland, NG Varshavsky, A AF Grigoryev, S Stewart, AE Kwon, YT Arfin, SM Bradshaw, RA Jenkins, NA Copeland, NG Varshavsky, A TI A mouse amidase specific for N-terminal asparagine - The gene, the enzyme, and their function in the N-end rule pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID UBIQUITIN-DEPENDENT PROTEOLYSIS; SHORT-LIVED PROTEIN; SACCHAROMYCES-CEREVISIAE; DEGRADATION SIGNAL; RECOGNITION COMPONENT; TRANSCRIPTION FACTORS; MULTIUBIQUITIN CHAIN; ESCHERICHIA-COLI; BINDING-PROTEINS; MESSENGER-RNA AB The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. In both fungi and mammals, the tertiary destabilizing N-terminal residues asparagine and glutamine function through their conversion, by enzymatic deamidation, into the secondary destabilizing residues aspartate and glutamate, whose destabilizing activity requires their enzymatic conjugation to arginine, one of the primary destabilizing residues. We report the isolation and analysis of a mouse cDNA and the corresponding gene (termed Ntan1) that encode a 310-residue amidohydrolase (termed Nt(N)-amidase) specific for N-terminal asparagine, The similar to 17-kilobase pair Ntan1 gene is located in the proximal region of mouse chromosome 16 and contains 10 exons ranging from 54 to 177 base pairs in length. The similar to 1.4 kilobase pair Ntan1 mRNA is expressed in all of the tested mouse tissues and cell lines and is down-regulated upon the conversion of myoblasts into myotubes. The Ntan1 promoter is located similar to 500 base pairs upstream of the Ntan1 start codon. The deduced amino acid sequence of mouse Nt(N)-amidase is 88% identical to the sequence of its porcine counterpart, but bears no significant similarity to the sequence of the NTA1-encoded N-terminal amidohydrolase of the yeast Saccharomyces cerevisiae, which can deamidate either N-terminal asparagine or glutamine. The expression of mouse Nt(N)-amidase in S. cerevisiae nta1 Delta was used to verify that Nt(N)-amidase retains its asparagine selectivity in. vivo and can implement the asparagine-specific subset of the N-end rule. Further dissection of mouse Ntan1, including its null phenotype analysis, should illuminate the functions of the N-end rule, most of which are still unknown. C1 CALTECH, DIV BIOL, PASADENA, CA 91125 USA. UNIV CALIF IRVINE, COLL MED, DEPT BIOL CHEM, IRVINE, CA 92717 USA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. RI Bradshaw, Ralph/K-1515-2013 FU NIDDK NIH HHS [DK32461, DK39520] NR 86 TC 57 Z9 58 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 8 PY 1996 VL 271 IS 45 BP 28521 EP 28532 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VU033 UT WOS:A1996VU03300081 PM 8910481 ER PT J AU Wang, Q Forlino, A Marini, JC AF Wang, Q Forlino, A Marini, JC TI Alternative splicing in COL1A1 mRNA leads to a partial null allele and two in-frame forms with structural defects in non-lethal osteogenesis imperfecta SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POINT MUTATIONS; MESSENGER-RNA; COLLAGEN; PROCOLLAGEN; CHAIN; GENE; DELETION; DNA; HETEROGENEITY; TRANSLATION AB We have identified a novel multiexon genomic deletion in one COL1A1 collagen allele that results in three alternative forms of mutant mRNA. This mutation occurs in a 9-year-old girl and her father, both affected with severe type III osteogenesis imperfecta (OI). We previously reported detection of a mismatch in their alpha 1(I) amino acids 558-861 region by RNA/RNA hybrid analysis (Orange, D. K., Gottesman, G. S., Lewis, M. B., and Marini, J. C. (1990) Nucleic Acids Res. 18, 4227-4286). Single Strand Conformational Polymorphism further localized the mRNA mutation to the amino acids 579-679 coding region. At the gene level, polymerase chain reaction (PCR) amplification of patient leukocyte DNA from the exon 33-38 region yielded the normal 1004-base pair (bp) fragment and an additional 442-bp fragment. Sequencing of the shorter genomic PCR product confirmed the presence of a 562-bp deletion, extending from the last 3 nucleotides (nt) of exon 34 to 156 nt from the 3'-end of intron 36. The genomic deletion was also detected in the clinically normal grandmother, who was confirmed to be a mosaic carrier. PCR amplification and RNase protection experiments were used to investigate the mRNA structure and occurrence of alternative splicing. One form of the mutant cDNA has a deletion with end points that are identical to the genomic deletion. This results in a combination deletion/insertion, with a deletion of amino acids 603-639 followed by an insertion of 156 nt from the 3'-end of intron 36. In addition, we found two alternatively spliced forms. One form uses a cryptic donor site in exon 34 and the exon 37 acceptor. The second form uses the normal exon 32 splice donor and exon 37 acceptor. Use of the cryptic donor results in a coding sequence that is out-of-frame. Both the retained intron form and the use of the exon 32 donor site result in coding sequences that are in-frame. This is the first report of a collagen defect in OI with alternative splicing generating both in-frame and out-of frame forms of mRNA. Although the in-frame forms constitute more than 60% of the mRNA from the mutant allele, no mutant protein chain was identified. Collagen produced by cultured OI osteoblasts showed a significant increase in the relative amount of type III collagen but no mutant alpha 1(I) chain. C1 NICHHD,SECT CONNECT TISSUE DISORDERS,HERITABLE DISORDERS BRANCH,NIH,BETHESDA,MD 20892. RI Forlino, Antonella/H-5385-2015 OI Forlino, Antonella/0000-0002-6385-1182 NR 24 TC 13 Z9 14 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 NOV 8 PY 1996 VL 271 IS 45 BP 28617 EP 28623 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VU033 UT WOS:A1996VU03300093 PM 8910493 ER PT J AU Zhang, WY Gaynor, PM Kruth, HS AF Zhang, WY Gaynor, PM Kruth, HS TI Apolipoprotein E produced by human monocyte-derived macrophages mediates cholesterol efflux that occurs in the absence of added cholesterol acceptors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HIGH-DENSITY-LIPOPROTEINS; MOUSE MACROPHAGES; APOPROTEIN-E; DIFFERENT MECHANISMS; CA++ ANTAGONISTS; E GENE; A-I; EXPRESSION; SECRETION; PROTEIN AB Human monocyte-derived macrophages can efflux accumulated cholesterol without exogenously added cholesterol accepters (Kruth, H. S., Skarlatos, S. I., Gaynor, P. M., and Gamble, W. (1994) J. Biol. Chem. 269, 24511-24518). Most of the effluxed cholesterol accumulates in the medium as apolipoprotein E-discoidal lipid particles. In the current study, we determined whether and to what degree cholesterol efflux from human monocyte-macrophages depended on apolipoprotein E secretion. Unexpectedly, 2-week-old differentiated monocyte-macrophages secreted similar amounts of apolipoprotein E without or with cholesterol enrichment. Apolipoprotein E mRNA levels in these macrophages were not increased by cholesterol enrichment and were comparable with levels in HepG2 cells. Without cholesterol enrichment, monocyte-macrophages secreted lipid-poor apolipoprotein E with a density > 1.21 g/ml. By contrast, cholesterol enrichment of monocyte macrophages induced the association of apoE with phospholipid and cholesterol to form discoidal particles that floated at densities of 1.08-1.10 g/ml. An anti-apolipoprotein E monoclonal antibody added to the culture medium significantly inhibited cholesterol and phospholipid efflux from the monocyte-macrophages. This showed that apolipoprotein E was required for most of the cholesterol efflux, and that apolipoprotein E did not leave macrophages with lipid but rather associated with lipid after it was secreted. Thus, 1) apolipoprotein E was constitutively secreted by differentiated human monocyte-macrophages, 2) apolipoprotein E only formed discoidal particles following macrophage cholesterol enrichment, 3) apolipoprotein E was necessary for cholesterol efflux to occur in the absence of added cholesterol accepters and, in addition 4) the level of macrophage unesterified cholesterol was not rate-limiting for this cholesterol efflux, and 5) net phospholipid synthesis occurred in macrophages secondary to apoE-mediated loss of macrophage phospholipid. In conclusion, apolipoprotein E functions in an autocrine pathway that mediates cholesterol efflux from human monocyte-derived macrophages. C1 NIH,NHLBI,SECT EXPT ATHEROSCLEROSIS,BETHESDA,MD 20892. NR 33 TC 121 Z9 121 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 8 PY 1996 VL 271 IS 45 BP 28641 EP 28646 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VU033 UT WOS:A1996VU03300097 PM 8910497 ER PT J AU Tycko, R Weliky, DP Berger, AE AF Tycko, R Weliky, DP Berger, AE TI Investigation of molecular structure in solids by two-dimensional NMR exchange spectroscopy with magic angle spinning SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; ALANYL-GLYCYL-GLYCINE; STATE NMR; ROTATING SOLIDS; SIDEBAND INTENSITIES; CRYSTAL-STRUCTURE; SPIN-1/2 NUCLEI; SPECTRA; CONFORMATION; PEPTIDES AB An approach to the investigation of molecular structures in disordered solids, using two-dimensional (2D) nuclear magnetic resonance (NMR) exchange spectroscopy with magic angle spinning (MAS)I is described. This approach permits the determination of the relative orientation of two isotopically labeled chemical groups within a molecule in an unoriented sample, thus placing strong constraints on the molecular conformation. Structural information is contained in the amplitudes of crosspeaks in rotor-synchronized 2D MAS exchange spectra that connect spinning sideband Lines of the two labeled sites. The theory for calculating the amplitudes of spinning sideband crosspeaks in 2D MAS exchange spectra, in the limit of complete magnetization exchange between the labeled sites, is presented in detail. A new technique that enhances the sensitivity of 2D MAS exchange spectra to molecular structure, called orientationally weighted 2D MAS exchange spectroscopy, is introduced. Symmetry principles that underlie the construction of pulse sequences for orientationally weighted 2D MAS exchange spectroscopy are explained. Experimental demonstrations of the utility of 2D MAS exchange spectroscopy in structural investigations of peptide and protein backbone conformations are carried out on a model C-13-labeled tripeptide, L-alanylglycylglycine. The dihedral angles phi and psi that characterize the peptide backbone conformation at Gly-2 are obtained accurately from the orientationally weighted and unweighted 2D C-13 NMR exchange spectra. (C) 1996 American Institute of Physics. C1 USN,CTR SURFACE WARFARE,DAHLGREN,VA 22448. RP Tycko, R (reprint author), NIDDKD,CHEM PHYS LAB,NIH,BLDG 2,BETHESDA,MD 20892, USA. NR 55 TC 81 Z9 82 U1 2 U2 8 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD NOV 8 PY 1996 VL 105 IS 18 BP 7915 EP 7930 DI 10.1063/1.472708 PG 16 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA VQ841 UT WOS:A1996VQ84100005 ER PT J AU Ito, Y Ma, Y AF Ito, Y Ma, Y TI pH-zone-refining countercurrent chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Review DE reviews; countercurrent chromatography; pH-Zone-refining countercurrent chromatography; amino acids; peptides; xanthenes; alkaloids; catecholamines; proteins ID LIQUID PARTITION CHROMATOGRAPHY; PREPARATIVE SEPARATION; ELUTION CENTRIFUGE; SOLID SUPPORT; STANDARDIZATION; COMPONENTS; STAINS; ACIDS; DYES AB A recently developed preparative technique, pH-zone-refining countercurrent chromatography (CCC), separates organic acids and bases according to their pK(a) and hydrophobicity. The hydrodynamic mechanism of pH-zone-refining CCC is illustrated in two elution modes along with a simple mathematical analysis. Separations include acidic and basic derivatives of amino acids and peptides, hydroxyxanthene dyes, alkaloids, indole auxins, and structural and geometrical isomers. Tn addition, recently developed affinity ligand separations of enantiomers, polar catecholamines, and free peptides are also described. Technical guidance is provided for interested users so that they can conduct a systematic search for the optimum solvent system and experimental conditions. Advantages as well as limitations of the present technique are discussed. RP Ito, Y (reprint author), NHLBI,BIOPHYS CHEM LAB,NIH,BLDG 10,RM 7N322 10 CENTER DR MSC 1676,BETHESDA,MD 20892, USA. NR 53 TC 102 Z9 113 U1 7 U2 32 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 NOV 8 PY 1996 VL 753 IS 1 BP 1 EP 36 DI 10.1016/S0021-9673(96)00565-1 PG 36 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA VW225 UT WOS:A1996VW22500001 PM 8962503 ER PT J AU Jiang, JL vanRhee, AM Melman, N Ji, XD Jacobson, KA AF Jiang, JL vanRhee, AM Melman, N Ji, XD Jacobson, KA TI 6-phenyl-1,4-dihydropyridine derivatives as potent and selective A(3) adenosine receptor antagonists SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MAST-CELLS; MOLECULAR-CLONING; RAT-BRAIN; CHEMISTRY AB An approach to designing dihydropyridines that bind to adenosine receptors without binding to L-type calcium channels has been described. 1,4-Dihydropyridine derivatives substituted with beta-styryl or phenylethynyl groups at the 4-position and aryl groups at the 6-position were synthesized and found to be selective for human A(3) receptors. Combinations of methyl, ethyl, and benzyl esters were included at the 3- and 5-positions. Affinity was determined in radioligand binding assays at rat brain A(1) and A(2A) receptors using [H-3]-(R)-PIA [[H-3]-(R)-N-6-(phenylisopropyl)adenosine] and [H-3]CGS 21680 [[H-3]-2-[[4-(2-carboxymethyl)phenyl]ethylamino]-5'-(N-ethyl carbamoyl)adenosine], respectively. Affinity was determined at cloned human and rat A(3) receptors using [I-125]AB-MECA [N-6-(4-amino-3-iodobenzyl)-5'-(N-methycarbonyl)adenosine]. Structure-activity analysis indicated that substitution of the phenyl ring of the beta-styryl group but not of the 6-phenyl substituent was tolerated in A(3) receptor selective agents. Replacement of the 6-phenyl ring with a 3-thienyl or 3-furyl group reduced the affinity at A(3) receptors by 4- and g-fold, respectively. A 5-benzyl ester 4-trans-beta-styryl derivative, 26, with a K-i value of 58.3 nM at A(3) receptors, was >1700-fold selective vs either A(1) receptors or A(2A) receptors. Shifting the benzyl ester to the 3-position lowered the affinity at A(3) receptors 3-fold. A 5-benzyl, 3-ethyl ester 4-phenylethynyl derivative, 28, displayed a K-i value of 31.4 nM at A(3) receptors and 1300-fold selectivity vs A(1) receptors. The isomeric 3-benzyl, 5-ethyl diester was >600-fold selective for A(3) receptors. Oxidation of 28 to the corresponding pyridine derivative reduced affinity at A(3) receptors by 88-fold and slightly increased affinity at A(1) receptors. C1 NIDDK,LBC,MOL RECOGNIT SECT,NATL INST HLTH,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 32 TC 67 Z9 67 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 8 PY 1996 VL 39 IS 23 BP 4667 EP 4675 DI 10.1021/jm960457c PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA VR624 UT WOS:A1996VR62400018 PM 8917655 ER PT J AU EmmertBuck, MR Bonner, RF Smith, PD Chuaqui, RF Zhuang, ZP Goldstein, SR Weiss, RA Liotta, LA AF EmmertBuck, MR Bonner, RF Smith, PD Chuaqui, RF Zhuang, ZP Goldstein, SR Weiss, RA Liotta, LA TI Laser capture microdissection SO SCIENCE LA English DT Article ID POLYMERASE CHAIN-REACTION; GENE-EXPRESSION; CLONAL ANALYSIS; ALLELIC LOSS; BREAST; CARCINOMAS; LESIONS; TISSUE AB Laser capture microdissection (LCM) under direct microscopic visualization permits rapid one-step procurement of selected human cell populations from a section of complex, heterogeneous tissue. In this technique, a transparent thermoplastic film (ethylene vinyl acetate polymer) is applied to the surface of the tissue section on a standard glass histopathology slide; a carbon dioxide laser pulse then specifically activates the film above the cells of interest. Strong focal adhesion allows selective procurement of the targeted cells. Multiple examples of LCM transfer and tissue analysis, including polymerase chain reaction amplification of DNA and RNA, and enzyme recovery from transferred tissue are demonstrated. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,NATL CTR RES RESOURCES,BETHESDA,MD 20892. RI Bonner, Robert/C-6783-2015 NR 20 TC 1659 Z9 1737 U1 4 U2 104 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 8 PY 1996 VL 274 IS 5289 BP 998 EP 1001 DI 10.1126/science.274.5289.998 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VR792 UT WOS:A1996VR79200054 PM 8875945 ER PT J AU Ambrosio, E Tella, SR Goldberg, SR Schindler, CW Erzouki, H Elmer, GI AF Ambrosio, E Tella, SR Goldberg, SR Schindler, CW Erzouki, H Elmer, GI TI Cardiovascular effects of cocaine during operant cocaine self-administration SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE cocaine; heart rate; blood pressure; self-administration ID CENTRAL-NERVOUS-SYSTEM; CONSCIOUS SQUIRREL-MONKEYS; NEURONAL MONOAMINE UPTAKE; RATS; MECHANISMS; RESPONSES; STIMULATION; HUMANS; BRAIN AB The aim of this study was to investigate the acute and chronic effects of cocaine self-administration behavior on cardiovascular function. Mean blood pressure and heart rate were measured by radio-telemetry during several experimental conditions. Initial control studies eliminated possible confounds related to the effects of saline injections and operant responding on heart rate and blood pressure. When rats were first allowed to self-administer 0.5-mg/kg injections of cocaine (FR(fixed ratio)10:TO 30 s), there was a significant increase in blood pressure. Tolerance developed to this effect within 3 daily sessions. A significant decrease in blood pressure and heart rate was observed during saline-substitution sessions. Increasing the injection dose of cocaine (1.0, 2.0 and 4.0 mg/kg per injection) did not produce a dramatic increase in blood pressure or heart rate despite significant cumulative cocaine intake (20-27 mg/kg). The cardiovascular effects of cocaine administration did not approach magnitudes previously reported. The results of the current study suggest that operant-conditioned behavior and/or the direct reinforcing effects of cocaine modulates the cardiovascular effects of cocaine. C1 NIDA,BEHAV PHARMACOL & GENET SECT,DIV INTRAMURAL RES,NIH,BALTIMORE,MD 21224. GEORGETOWN UNIV,SCH MED,DEPT PHARMACOL,WASHINGTON,DC 20007. FU NIDA NIH HHS [IR29DA08830] NR 37 TC 14 Z9 14 U1 4 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD NOV 7 PY 1996 VL 315 IS 1 BP 43 EP 51 DI 10.1016/S0014-2999(96)00574-2 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VW083 UT WOS:A1996VW08300006 PM 8960863 ER PT J AU Stratakis, CA Mitsiades, NS Chrousos, GP Margioris, AN AF Stratakis, CA Mitsiades, NS Chrousos, GP Margioris, AN TI Dopamine affects the in vitro basal secretion of rat placenta opioids in an opioid and dopamine receptor type-specific manner SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE dopamine; placenta; beta-endorphin; dynorphin; perfusion; (rat) ID MESSENGER-RIBONUCLEIC-ACID; TERM TROPHOBLASTIC CELLS; BETA-ENDORPHIN; ADENYLATE-CYCLASE; GENE-EXPRESSION; DYNORPHIN; RELEASE; PEPTIDES; INVITRO; INHIBITION AB Opioid peptides and their receptors are present in the placenta of many species. Dopamine plays an important role in the regulation of opioid release in the nervous system and it may play a similar role in placenta since dopamine receptors are also present in this tissue. The aim of the present work was to examine the effect of dopamine on the basal release of rat placental opioids. The effect of several dopamine receptor agonists and antagonists was tested on the release of immunoreactive beta-endorphin and immunoreactive dynorphin from perfused rat placenta fragments. We found that dopamine and apomorphine stimulated the secretion of immunoreactive beta-endorphin in a dose-dependent manner. The selective D-1 dopamine receptor agonist (+)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride or SKF-38393 reproduced the effect of dopamine while the selective D-1 dopamine receptor antagonist R(+)-7-chloro-8-hpdroxy-3-methyl-1-phenyl 1,2,3,4,5-tetrahydro-1H-benzazepine hydrochloride or SCH-23390, prevented the dopamine- and SKF-38393-induced increase of immunoreactive beta-endorphin secretion. The selective and potent D-2 dopamine receptor agonist (+/-)-2-(N- phenylethyl-N-propyl)amino-5-hydroxytetralin hydrochloride or PPHT had no effect on immunoreactive beta-endorphin. Finally, none of the agonists tested had any effect on the in vitro secretion of placental immunoreactive dynorphin. Our results suggest that dopamine affects the basal release of placental opioids in an opioid and dopamine receptor-specific manner, its effect being different from the effect it exerts on beta-endorphin in the rat neurointermediate pituitary lobe. C1 UNIV CRETE,SCH MED,DEPT CLIN CHEM,GR-71110 IRAKLION,GREECE. NICHHD,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. NR 45 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD NOV 7 PY 1996 VL 315 IS 1 BP 53 EP 58 DI 10.1016/S0014-2999(96)00577-8 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VW083 UT WOS:A1996VW08300007 PM 8960864 ER PT J AU Misik, V Riesz, P AF Misik, V Riesz, P TI Nitric oxide formation by ultrasound in aqueous solutions SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID WATER; NO; SONOLUMINESCENCE; CAVITATION; SONOLYSIS; EXCHANGE; NITRATE; OXYGEN AB In this study we demonstrate formation of nitric oxide in aqueous nitrogen-containing solutions exposed to 50 kHz cavitation-producing ultrasound (standard bath sonicator) using electron paramagnetic resonance detection of (NO)-N-. by trapping with the sodium N-methyl-D-glucamine dithiocarbamate iron(II) complex ((MGDFe2+) or by measuring the conversion of the nitronyl nitroxide, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-3- oxide-1-oxyl (carboxy-PTIO), to the imino nitroxide, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl. The (MGDFe2+ complex which was used in most experiments was suitable for (NO)-N-. detection over a wide pH range (pH 3-7.8: the working range for carboxy-PTIO was pH 6-8.5), and the measured rate constant of (MGDFe2+ reaction with (NO)-N-. was 2.3 times higher than for carboxy-PTIO. In air-saturated water the rate of (NO)-N-. production by ultrasound was similar to 0.5 mu M/min. The presence of dissolved oxygen was not essential for production of (NO)-N-.; the highest yields of (NO)-N-. (similar to 1.2 mu M (NO)-N-./min) were found under an atmosphere of 40% N-2 and 60% argon. The formation of (NO)-N-. by ultrasound in aqueous solutions can be understood in terms of combustion chemistry-type reactions occurring inside the ''hot'' collapsing cavitation bubbles. We also show that other N-containing molecules can serve as a source of nitrogen for (NO)-N-. production. The possibility of ultrasound-mediated (NO)-N-. formation to alleviate hypoxia of tumors should be explored. C1 NCI,RADIAT BIOL BRANCH,NIH,BETHESDA,MD 20892. NR 42 TC 27 Z9 27 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3654 J9 J PHYS CHEM-US JI J. Phys. Chem. PD NOV 7 PY 1996 VL 100 IS 45 BP 17986 EP 17994 DI 10.1021/jp961522x PG 9 WC Chemistry, Physical SC Chemistry GA VR570 UT WOS:A1996VR57000043 ER PT J AU Kunkel, TA Wilson, SH AF Kunkel, TA Wilson, SH TI DNA repair - Push and pull of base flipping SO NATURE LA English DT Editorial Material ID ESCHERICHIA-COLI RP Kunkel, TA (reprint author), NIEHS,STRUCT BIOL LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 12 TC 16 Z9 16 U1 0 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD NOV 7 PY 1996 VL 384 IS 6604 BP 25 EP 26 DI 10.1038/384025a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VR219 UT WOS:A1996VR21900032 PM 8900270 ER PT J AU Devchand, PR Keller, H Peters, JM Vazquez, M Gonzalez, FJ Wahli, W AF Devchand, PR Keller, H Peters, JM Vazquez, M Gonzalez, FJ Wahli, W TI The PPAR alpha-leukotriene B-4 pathway to inflammation control SO NATURE LA English DT Article ID PROLIFERATOR-ACTIVATED RECEPTOR; RETINOID-X RECEPTOR; PEROXISOME PROLIFERATOR; FATTY-ACIDS; CDNA CLONING; HETERODIMER FORMATION; TARGETED DISRUPTION; BETA-OXIDATION; EXPRESSION; GAMMA AB Inflammation is a local immune response to 'foreign' molecules, infection and injury. Leukotriene B-4, a potent chemotactic agent that initiates, coordinates, sustains and amplifies the inflammatory response, is shown to be an activating ligand for the transcription factor PPAR alpha. Because PPAR alpha regulates the oxidative degradation of fatty acids and their derivatives, like this lipid mediator, a feedback mechanism is proposed that controls the duration of an inflammatory response and the clearance of leukotriene B-4 in the liver. Thus PPAR alpha offers a new route to the development of anti- or pro-inflammatory reagents. C1 UNIV LAUSANNE, INST BIOL ANIM, CH-1015 LAUSANNE, SWITZERLAND. NCI, MOL CARCINOGENESIS LAB, NIH, BETHESDA, MD 20892 USA. RI Peters, Jeffrey/D-8847-2011; Wahli, Walter/B-1398-2009 OI Wahli, Walter/0000-0002-5966-9089 NR 43 TC 971 Z9 987 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 7 PY 1996 VL 384 IS 6604 BP 39 EP 43 DI 10.1038/384039a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VR219 UT WOS:A1996VR21900046 PM 8900274 ER PT J AU Kustov, AA Robinson, DL AF Kustov, AA Robinson, DL TI Shared neural control of attentional shifts and eye movements SO NATURE LA English DT Article ID MONKEY SUPERIOR COLLICULUS; VISUAL-ATTENTION; STIMULATION; MACAQUES; CELLS; LOCALIZATION; SACCADES AB WE are able to move visual attention away from the direction of gaze, fixating on one object while attending to something else at a different location. Within the region of peripheral vision, It has been widely assumed that the attentional neural systems are separate from the motor systems, but some studies challenge this idea(1-5). It has now been suggested that the attentional system is part of the premotor processing in the brain(6). This model proposes that attentional processes evolved as part of the motor systems, with isolated attentional shifts representing an artificial separation of a natural linkage, Here we test how attentional shifts might be linked to the preparations for making saccadic eye movements. We studied the superior colliculus in monkeys as they shifted their attention during different tasks, and found that each attentional shift is associated with eye-movement preparation. C1 NEI,SENSORIMOTOR RES LAB,SECT VISUAL BEHAV,BETHESDA,MD 20892. NR 25 TC 429 Z9 433 U1 3 U2 23 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD NOV 7 PY 1996 VL 384 IS 6604 BP 74 EP 77 DI 10.1038/384074a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VR219 UT WOS:A1996VR21900057 PM 8900281 ER PT J AU Aroca, P Mahadevan, D Santos, E AF Aroca, P Mahadevan, D Santos, E TI Functional interactions between isolated SH2 domains and insulin/Ras signaling pathways of Xenopus oocytes: Opposite effects of the carboxy- and amino-terminal SH2 domains of p85 PI 3-kinase SO ONCOGENE LA English DT Article DE SH2; Ras; insulin signaling; p85 alpha PI 3-kinase; Xenopus ID RECEPTOR TYROSINE KINASES; PHOSPHOLIPASE-C-GAMMA; PHOSPHATIDYLINOSITOL 3-KINASE; MEIOTIC MATURATION; ONCOGENE PRODUCT; BETA-RECEPTOR; HIGH-AFFINITY; RAS PROTEINS; SPECIFICITY; ACTIVATION AB Purified amino-terminal Src homology 2 (SH2) domains of GAP, PLC gamma 1 and the p85 alpha subunit of PI 3-kinase, as well as the carboxy-terminal SH2 domain of the latter protein and the unique SH2 domain of Grb2, were injected into full grown, stage VI Xenopus laevis oocytes, None of the injected domains showed any effect when injected alone, nor did they affect the rate of GVBD induced by progesterone, an adenylate cyclase-dependent process, On the other hand, the unique Grb2 SH2 domain and all N-terminal SH2 domains injected inhibited to various degrees the rate of insulin-induced GVBD, a tyrosine kinase dependent pathway, Interestingly, and in contrast to the behavior shown by the N-terminal domain of the same molecule, the C-terminal SH2 domain of p85 did not inhibit, but slightly accelerated the rate of GVBD induced by insulin, Furthermore, whereas the Grb SH2 domain and all N-terminal SH2 domains tested failed to co-operate with normal Ras protein to induce GVBD, the C-terminal SH2 domain of p85 alpha exhibited significant synergy when coinjected with normal Pas protein, indicating that the C- and N-terminal SH2 domains of p85 alpha exert opposite (positive and negative, respectively) regulatory roles in the control of oocyte insulin/Ras signaling pathways, Our results demonstrate that the purified, isolated SH2 domains retain structural and functional specificity and that Xenopus oocytes constitute an useful biological system to analyse their functional role in tyrosine kinase signaling pathways. C1 NCI,DBS,CELLULAR & MOL BIOL LAB,BETHESDA,MD 20892. NR 52 TC 14 Z9 14 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 7 PY 1996 VL 13 IS 9 BP 1839 EP 1846 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VR795 UT WOS:A1996VR79500002 PM 8934529 ER PT J AU Herzog, CR Soloff, EV McDoniels, AL Tyson, FL Malkinson, AM HaugenStrano, A Wiseman, RW Anderson, MW You, M AF Herzog, CR Soloff, EV McDoniels, AL Tyson, FL Malkinson, AM HaugenStrano, A Wiseman, RW Anderson, MW You, M TI Homozygous codeletion and differential decreased expression of p15(INK4b) p16(INK4a)-alpha and p16(INK4a)-beta in mouse lung tumor cells SO ONCOGENE LA English DT Article DE p15(INK4b); p16(INK4a)-alpha; p16(INK4a)-beta; mouse lung; tumor suppressor gene ID KINASE-4 INHIBITOR GENE; SUPPRESSOR GENE; P16 MTS1; FAMILIAL MELANOMA; CDK6 INHIBITOR; HUMAN CANCERS; CYCLE ARREST; MUTATIONS; METHYLATION; DELETIONS AB The genes of murine cyclin D-dependent kinase inhibitors, p15(INK4b) and p16(INK4a), are located in a region of chromosome 4 where overlapping deletions were found in lung adenocarcinomas, The p16(INK4a) gene uniquely consists of alternative first exons (E1 alpha and E1 beta), which are spliced to exon 2 in alternative reading frames to either encode p16(INK4a) (alpha form) or another potential tumor suppressor, p19(ARF) (beta form), We examined 99 lung adenocarcinomas of C3H/HeJ x A/J F-1(C3AF(1)) and A/J x C3H/HeJ F-1(AC3F(1)) mouse hybrids and 18 (13 metastatic, 5 nonmetastatic) tumorigenic mouse lung epithelial cell lines for p15(INK4b) and p16(INK4a) gene inactivation, Homozygous codeletion occurred in eight of the 13 (62%) metastatic, four of the five (80%) nonmetastatic cell lines, but in only six of 99 (6%) adenocarcinomas. Neither p15(INK4b) nor p16(INK4a) gene was individually deleted in any of the tumors or cell lines, and all deletions of the p16(INK4a) gene extended into exon 2, which would be expected to disrupt the functions of both p16(INK4a) and p19(ARF). We also detected no intragenic mutations of either gene in 44 tumors that displayed loss of heterozygosity at the p16(INK4a) locus or in any of the cell lines, Transcript levels of p16(INK4a)-alpha, p16(INK4a)-beta and p15(INK4b) also were examined in each of the cell lines that retained copies of these genes, Whereas an immortal mouse lung epithelial cell line (E10) and two metastatic tumor cell lines (LM1 and E9) expressed p16(INK4a)-beta and p15(INK4b) mRNA, the a transcript of p16(INK4a) was detected in only the LM1 cell line. These results suggest that both p15(INK4b) and p16(INK4a) (alpha and beta) are targets of inactivation in mouse lung tumorigenesis. C1 MED COLL OHIO,DEPT PATHOL,TOLEDO,OH 43699. ST MARYS HOSP,CANC RES INST,GRAND JCT,CO 81501. UNIV COLORADO,HLTH SCI CTR,SCH PHARM,MOL TOXICOL PROGRAM,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,SCH PHARM,COLORADO CANC CTR,DENVER,CO 80262. NIEHS,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. FU NCI NIH HHS [CA58554] NR 40 TC 66 Z9 67 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 7 PY 1996 VL 13 IS 9 BP 1885 EP 1891 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VR795 UT WOS:A1996VR79500007 PM 8934534 ER PT J AU Levine, R DerSimonian, R AF Levine, R DerSimonian, R TI Effects of calcium supplementation on pregnancy-induced hypertension SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP Levine, R (reprint author), NICHHD, BETHESDA, MD 20892 USA. NR 5 TC 4 Z9 4 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 6 PY 1996 VL 276 IS 17 BP 1387 EP 1387 DI 10.1001/jama.276.17.1387 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VQ464 UT WOS:A1996VQ46400020 PM 8892712 ER PT J AU Fisher, B Dignam, J Bryant, J DeCillis, A Wickerham, DL Wolmark, N Costantino, J Redmond, C Fisher, ER Bowman, DM Deschenes, L Dimitrov, NV Margolese, RG Robidoux, A Shibata, H Terz, J Paterson, AHG Feldman, MI Farrar, W Evans, J Lickley, HL AF Fisher, B Dignam, J Bryant, J DeCillis, A Wickerham, DL Wolmark, N Costantino, J Redmond, C Fisher, ER Bowman, DM Deschenes, L Dimitrov, NV Margolese, RG Robidoux, A Shibata, H Terz, J Paterson, AHG Feldman, MI Farrar, W Evans, J Lickley, HL TI Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ADJUVANT TAMOXIFEN; RANDOMIZED TRIAL; RESISTANCE; RADIOTHERAPY; WITHDRAWAL; RADIATION; MORBIDITY; WOMEN; RAT AB Background: In 1982, the National Surgical Adjuvant Breast and Bowel Project initiated a randomized, double-blinded, placebo-controlled trial (B-14) to determine the effectiveness of adjuvant tamoxifen therapy in patients with primary operable breast cancer who had estrogen receptor-positive tumors and no axillary lymph node involvement. The findings indicated that tamoxifen therapy provided substantial benefit to patients with early stage disease. However, questions arose about how long the observed benefit would persist, about the duration of therapy necessary to maintain maximum benefit, and about the nature and severity of adverse effects from prolonged treatment. Purpose: We evaluated the outcome of patients in the B-14 trial through 10 years of follow-up. In addition, the effects of 5 years versus more than 5 years of tamoxifen therapy were compared. Methods: In the trial, patients were initially assigned to receive either tamoxifen at 20 mg/day (n = 1404) or placebo (n = 1414). Tamoxifen-treated patients who remained disease free after 5 years of therapy were then reassigned to receive either another 5 years of tamoxifen (n = 322) or 5 years of placebo (n = 321). After the study began, another group of patients who met the same protocol eligibility requirements as the randomly assigned patients were registered to receive tamoxifen (n = 1211). Registered patients who were disease free after 5 years of treatment were also randomly assigned to another 5 years of tamoxifen (n = 261) or to 5 years of placebo (n = 249). To compare 5 years with more than 5 gears of tamoxifen therapy, data relating to all patients reassigned to an additional 5 years of the drug were combined. Patients who were not reassigned to either tamoxifen or placebo continued to be followed in the study. Survival, disease-free survival, and distant disease-free survival (relating to failure at distant sites) were estimated by use of the Kaplan-Meier method; differences between the treatment groups were assessed by use of the logrank test. The relative risks of failure (with 95% confidence intervals [CIs]) were determined by use of the Cox proportional hazards model. Reported P values are two-sided. Results: Through 10 years of follow-up, a significant advantage in disease-free survival (69% versus 57%, P<.0001; relative risk = 0.66; 95% CI = 0.58-0.74), distant disease-free survival (76% versus 67%, P<.0001; relative risk = 0.70; 95% CI = 0.61-0.81), and survival (80% versus 76%, P = .02; relative risk = 0.84; 95% CI = 0.71-0.99) was found for patients in the group first assigned to receive tamoxifen. The survival benefit extended to those 49 years of age or younger and to those 50 years of age or older. Tamoxifen therapy was associated with a 37% reduction in the incidence of contralateral (opposite) breast cancer (P = .007). Through 4 years after the reassignment of tamoxifen-treated patients to either continued-therapy or placebo groups, advantages in disease-free survival (92% versus 86%, P = .003) and distant disease-free survival (96% versus 90%, P = .01) were found for those who discontinued tamoxifen treatment. Survival was 96% for those who discontinued tamoxifen compared with 94% for those who continued tamoxifen treatment (P = .08). A higher incidence of thromboembolic events was seen in tamoxifen-treated patients (through 5 years, 1.7% versus 0.4%). Except for endometrial cancer, the incidence of second cancers was not increased with tamoxifen therapy. Conclusions and Implications: The benefit from 5 years of tamoxifen therapy persists through 10 years of follow-up. No additional advantage is obtained from continuing tamoxifen therapy for more than 5 years. C1 UNIV PITTSBURGH,NATL SURG ADJUVANT BREAST & BOWEL PROJECT,PITTSBURGH,PA. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT BIOSTAT,PITTSBURGH,PA 15261. UNIV PITTSBURGH,NSABP MED OVERSIGHT,PITTSBURGH,PA. ALLEGHENY GEN HOSP,PITTSBURGH,PA 15212. MED UNIV S CAROLINA,COLL MED,DEPT BIOMETRY & EPIDEMIOL,CHARLESTON,SC 29425. SHADYSIDE HOSP,INST PATHOL,PITTSBURGH,PA 15232. MANITOBA CANC FDN,WINNIPEG,MB,CANADA. ST SACRAMENT HOSP,QUEBEC CITY,PQ,CANADA. MICHIGAN STATE UNIV,DEPT MED,E LANSING,MI 48824. MCGILL UNIV,JEWISH GEN HOSP,MONTREAL,PQ H3T 1E2,CANADA. HOP HOTEL DIEU,MONTREAL,PQ,CANADA. ROYAL VICTORIA HOSP,MONTREAL,PQ H3A 1A1,CANADA. CITY HOPE NATL MED CTR,DUARTE,CA 91010. CROSS CANC INST,EDMONTON,AB T6G 1Z2,CANADA. BOSTON UNIV,BOSTON,MA 02215. OHIO STATE UNIV,COLUMBUS,OH 43210. GEISINGER MED CTR,DANVILLE,PA 17822. WOMENS COLL HOSP,TORONTO,ON M5S 1B2,CANADA. RP Fisher, B (reprint author), UNIV PITTSBURGH,SCH MED,3550 TERRACE ST,RM 914,PITTSBURGH,PA 15261, USA. FU NCI NIH HHS [U10CA12027, U10CA37377, U10CA39086] NR 39 TC 577 Z9 590 U1 1 U2 9 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 NOV 6 PY 1996 VL 88 IS 21 BP 1529 EP 1542 DI 10.1093/jnci/88.21.1529 PG 14 WC Oncology SC Oncology GA VQ465 UT WOS:A1996VQ46500010 PM 8901851 ER PT J AU Albanes, D Heinonen, OP Taylor, PR Virtamo, J Edwards, BK Rautalahti, M Hartman, AM Palmgren, J Freedman, LS Haapakoski, J Barrett, MJ Pietinen, P Malila, N Tala, E Liippo, K Salomaa, ER Tangrea, JA Teppo, L Askin, FB Taskinen, E Erozan, Y Greenwald, P Huttunen, JK AF Albanes, D Heinonen, OP Taylor, PR Virtamo, J Edwards, BK Rautalahti, M Hartman, AM Palmgren, J Freedman, LS Haapakoski, J Barrett, MJ Pietinen, P Malila, N Tala, E Liippo, K Salomaa, ER Tangrea, JA Teppo, L Askin, FB Taskinen, E Erozan, Y Greenwald, P Huttunen, JK TI alpha-tocopherol and beta-carotene supplements and lung cancer incidence in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study: Effects of base-line characteristics and study compliance SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; EPIDEMIOLOGIC EVIDENCE; COLORECTAL ADENOMAS; CLINICAL-TRIAL; ANTIOXIDANT; CANTHAXANTHIN; VEGETABLES; CLEARANCE; PROMOTION AB Background: Experimental and epidemiologic investigations suggest that alpha-tocopherol (the most prevalent chemical form of vitamin E found in vegetable oils, seeds, grains, nuts, and other foods) and beta-carotene (a plant pigment and major precursor of vitamin A found in many yellow, orange, and dark-green, leafy vegetables and some fruit) might reduce the risk of cancer, particularly lung cancer. The initial findings of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study) indicated, however, that lung cancer incidence was increased among participants who received beta-carotene as a supplement. Similar results were recently reported by the Beta-Carotene and Retinol Efficacy Trial (CARET), which tested a combination of beta-carotene and vitamin A. Purpose: We examined the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of lung canter across subgroups of participants in the ATBC Study defined by base-line characteristics (e.g., age, number of cigarettes smoked, dietary or serum vitamin status, and alcohol consumption), by study compliance, and in relation to clinical factors, such as disease stage and histologic type. Our primary purpose was to determine whether the pattern of intervention effects across subgroups could facilitate further interpretation of the main ATBC Study results and shed light on potential mechanisms of action and relevance to other populations. Methods: A total of 29 133 men aged 50-69 years who smoked fire ol more cigarettes daily were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), alpha-tocopherol and beta-carotene, or a placebo daily for 5-8 years (median, 6.1 gears). Data regarding smoking and other risk factors for lung cancer and dietary factor's were obtained at study entry, along with measurements of serum levels of alpha-tocopherol and beta-carotene. Incident cases of lung cancer (n = 894) were identified through the Finnish Cancer Registry and death certificates. Each lung cancer diagnosis was independently confirmed, and histology or cytology was available for 94% of the cases. Intervention effects were evaluated by use of survival analysis and proportional hazards models, All P values were derived from two-sided statistical tests. Results: No overall effect was observed for lung cancer from alpha-tocopherol supplementation (relative risk [RR] = 0.99; 95% confidence interval [CI] = 0.87-1.13; P = .86, logrank test). beta-Carotene supplementation was associated with increased lung cancer risk (RR = 1.16; 95% CI = 1.02-1.33; P = .02, logrank test). The beta-carotene effect appeared stronger, but not substantially different, in participants who smoked at least 20 cigarettes daily (RR = 1.25; 95% CI = 1.07-1.46) compared with those who smoked five to 19 cigarettes daily (RR = 0.97; 95% CI = 0.76-1.23) and in those with a higher alcohol intake (greater than or equal to 11 g of ethanol/day [just under one drink per day]; RR = 1.35; 95% CI = 1.01-1.81) compared with those with a lower intake (RR = 1.03; 95% CI = 0.85-1.24). Conclusions: Supplementation with alpha-tocopherol or beta-carotene does not prevent lung cancer ire older men who smoke. beta-carotene supplementation at pharmacologic levels may modestly increase lung cancer incidence in cigarette smokers, and this effect mag be associated with heavier smoking and higher alcohol intake. Implications: While the most direct way to reduce lung cancer risk is not to smoke tobacco, smokers should avoid high-dose beta-carotene supplementation. C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. UNIV HELSINKI,DEPT PUBL HLTH,FIN-00014 HELSINKI,FINLAND. NATL PUBL HLTH INST,HELSINKI,FINLAND. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. TURKU UNIV HOSP,DEPT DIS CHEST,FIN-20520 TURKU,FINLAND. FINNISH CANC REGISTRY,FIN-00170 HELSINKI,FINLAND. JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205. UNIV HELSINKI,SCH MED,FIN-00014 HELSINKI,FINLAND. RI Albanes, Demetrius/B-9749-2015; OI Palmgren, Juni/0000-0002-9031-8615 FU NCI NIH HHS [N01CN45165] NR 39 TC 538 Z9 553 U1 2 U2 32 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 NOV 6 PY 1996 VL 88 IS 21 BP 1560 EP 1570 DI 10.1093/jnci/88.21.1560 PG 11 WC Oncology SC Oncology GA VQ465 UT WOS:A1996VQ46500013 PM 8901854 ER PT J AU Chu, KC Tarone, RE Kessler, LG Ries, LAG Hankey, BF Miller, BA Edwards, BK AF Chu, KC Tarone, RE Kessler, LG Ries, LAG Hankey, BF Miller, BA Edwards, BK TI Recent trends in US breast cancer incidence, survival, and mortality rates SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID DEATH RATES; WHITE WOMEN; MAMMOGRAPHY; DIAGNOSIS; RELEVANCE; PATTERNS; ENGLAND; WALES AB Background: Clinical trials have demonstrated that use of mammographic screening and advances in therapy can improve prognosis for women with breast cancer. Purpose: We determined the trends in breast cancer mortality rates, as well as incidence and survival rates by extent of disease at diagnosis, for white women in the United States and considered whether these trends are consistent with widespread use of such beneficial medical interventions. Methods: We examined mortality data from the National Center for Health Statistics and incidence and survival data by extent of disease from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute, all stratified by patient age, using statistical-regression techniques to determine changes in the slope of trends over time. Results: The age-adjusted breast cancer mortality rate for U.S. white females dropped 6.8% from 1989 through 1993. A significant decrease in the slope of the mortality trend of approximately 2% per year was observed in every decade of age from 40 to 79 years of age. Trends in incidence rates were also similar among these age groups: localized disease rates increased rapidly from 1982 through 1987 and stabilized or increased more slowly thereafter; regional disease rates decreased after 1987; and distant disease rates have remained level over the past 20 years. Three-year relative survival rates increased steadily and significantly for both localized and regional disease from 1980 through 1989 in all ages, with no evidence of an increase in slope in the late 1980s. Implications: The decrease in the diagnosis of regional disease in the late 1980s in women over the age of 40 years likely reflects the increased use of mammography earlier in the 1980s. The increase in survival rates, particularly for regional disease, likely reflects improvements in systemic adjuvant therapy, Statistical modeling indicates that the recent drop in breast cancer mortality is too rapid to be explained only by the increased use of mammography; likewise, there has been no equivalent dramatic increase in survival rates that would implicate therapy alone. Thus, indications are that both are involved in the recent rapid decline in breast cancer mortality rates in the United States. C1 NCI,SPECIAL POPULAT STUDIES BRANCH,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. NCI,APPL RES BRANCH,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. NCI,CANC STAT BRANCH,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. NCI,CANC CONTROL RES PROGRAM,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. NCI,BIOSTAT BRANCH,DIV EPIDEMIOL & GENET,BETHESDA,MD 20892. NR 46 TC 303 Z9 314 U1 2 U2 9 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 NOV 6 PY 1996 VL 88 IS 21 BP 1571 EP 1579 DI 10.1093/jnci/88.21.1571 PG 9 WC Oncology SC Oncology GA VQ465 UT WOS:A1996VQ46500014 PM 8901855 ER PT J AU Lu, PJ Shieh, WR Rhee, SG Yin, HL Chen, CS AF Lu, PJ Shieh, WR Rhee, SG Yin, HL Chen, CS TI Lipid products of phosphoinositide 3-kinase bind human profilin with high affinity SO BIOCHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; ACANTHAMOEBA PROFILIN; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; SIGNAL-TRANSDUCTION; HUMAN-NEUTROPHILS; ACTIN; ACTIVATION; BETA; SITE; INCREASE AB To gain insight into the physiological function of phosphoinositide 3-kinase (PI 3-kinase) lipid products, this study examines the interactions of the D-3 phosphoinositides with profilin and the consequent effects on actin dynamics and phosphoinositide turnover. Profilin, a ubiquitous actin-regulating protein, plays a putative role in regulating actin assembly and PLC-gamma 1 signaling in light of its unique interactions with actin and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P-2]. Here we raise evidence that the affinity of profilin with the D-3 phosphoinositides is substantially higher than that of PtdIns(4,5)P-2. The dissociation constants (K-d) are estimated to be 1.1 mu M, 5.7 mu M, and 11 mu M for phosphatidylinositol 3,4-bisphosphate [PtdIns(3,4)P-2], phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P-3], and PtdIns(4,5)P-2, respectively. Spectroscopic data show that while all these phosphoinositides alter the tryptophan fluorescence of profilin in a similar fashion, the respective conformational effect on profilin is vastly different. Based on CD data, the alpha-helical contents of profilin in the presence of 8 molar equiv of PtdIns(4,5)P-2, PtdIns(3,4,5)P-3, and PtdIns(3,4)P-2 are 17.4%, 11.5%, and 1.4%, respectively, vis-a-vis 9.4% for profilin alone. In contrast, no appreciable change in the fluorescence and CD spectra is observed when related inositol phosphates such as Ins(1,4,5)P-3, Ins(1,3,4,5)P-4, or Ins(1,3,4)P-3 at comparable concentrations are tested. Evidence suggests that this differential recognition bears functional significance concerning the intricate roles of profilin and inositol lipids in modulating actin polymerization and PtdIns(4,5)P-2 turnover. The relative potency of individual phosphoinositides in offsetting the inhibitory effect of profilin on actin assembly is PtdIns(3,4)P-2, PtdIns(3,4,5)P-3 > PtdIns(4,5)P-2, consistent with their relative binding affinity with profilin. Moreover, the inhibitory effect of profilin on PLC-gamma 1-mediated PtdIns(4,5)P-2 hydrolysis is overcome by PtdIns(3,4)P-2 and PtdIns(3,4,5)P-3 through a combined effect of PLC-gamma 1 activation and preferential profilin binding. This D-3 phosphoinositide-mediated regulation may represent a new mechanism for controlling PtdIns(4,5)P-2 turnover by PLC-gamma 1. C1 UNIV KENTUCKY,DIV MED CHEM & PHARMACEUT,ASTECC FACIL,COLL PHARM,LEXINGTON,KY 40506. UNIV KENTUCKY,DEPT CLIN SCI,LEXINGTON,KY 40536. NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. UNIV TEXAS,SW MED CTR,DEPT PHYSIOL,DALLAS,TX 75235. FU NIGMS NIH HHS [R01 GM53448] NR 44 TC 106 Z9 107 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 5 PY 1996 VL 35 IS 44 BP 14027 EP 14034 DI 10.1021/bi961878z PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VR098 UT WOS:A1996VR09800019 PM 8909300 ER PT J AU Wright, JM Peoples, RW Weight, FF AF Wright, JM Peoples, RW Weight, FF TI Single-channel and whole-cell analysis of ethanol inhibition of NMDA-activated currents in cultured mouse cortical and hippocampal neurons SO BRAIN RESEARCH LA English DT Article DE N-methyl-D-aspartate; ethanol; single-channel recording; kinetic analysis; whole-cell recording; mouse, inbred strain C57BL/6 ID D-ASPARTATE RECEPTOR; ION CURRENT; RAT; GLYCINE; RELEASE; SLICES; BRAIN; ACETYLCHOLINE AB The effects of 0.1 to 500 mM ethanol on NMDA-activated currents were studied in primary cultures of mouse cortical and hippocampal neurons. In whole-cell recordings the IC(50)s for inhibition of NMDA-activated currents by ethanol were 129 mM +/- 20 mM in hippocampal neurons and 126 +/- 18 mM in cortical neurons. In single-channel recordings from excised outside-out patches of cortical neurons, ethanol inhibited total charge per minute with an IC50 of 174 +/- 23 mM, which was not significantly different from the IC(50)s for inhibition of whole-cell current. The reduction in mean open channel lifetime by ethanol was fit by the logistic equation with an apparent IC50 of 340 +/- 28 mM. Analysis of single-channel data indicated that ethanol inhibition of NMDA currents did not involve substantial changes in fast closed state kinetics, changes in open channel conductance, or block of the open channel. At the whole-cell IC50 of ethanol, mean open channel lifetime would decrease by 28% and frequency of opening would decline by 31% to account for the reduction in current. Single-channel data were consistent with ethanol being an allosteric modulator of gating which reduces agonist efficacy. C1 NIAAA, MOL & CELLULAR NEUROBIOL LAB, NIH, BETHESDA, MD 20892 USA. NR 49 TC 72 Z9 74 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 4 PY 1996 VL 738 IS 2 BP 249 EP 256 DI 10.1016/S0006-8993(96)00780-9 PG 8 WC Neurosciences SC Neurosciences & Neurology GA VU612 UT WOS:A1996VU61200009 PM 8955520 ER PT J AU Costell, M Sasaki, T Mann, K Yamada, Y Timpl, R AF Costell, M Sasaki, T Mann, K Yamada, Y Timpl, R TI Structural characterization of recombinant domain II of the basement membrane proteoglycan perlecan SO FEBS LETTERS LA English DT Article DE basement membrane; proteoglycan; recombinant protein; rod-like structure ID HEPARAN-SULFATE PROTEOGLYCAN; DENSITY-LIPOPROTEIN-RECEPTOR; EPIDERMAL-GROWTH-FACTOR; CELL-ADHESION MOLECULES; DIFFERENT PROTEINS; BINDING; LAMININ; MOUSE; GLYCOSYLATION; SEQUENCE AB Mouse perlecan domain II (325 residues), consisting of four cysteine-rich LA modules, one IG module and a link region, was obtained in purified form from a stably transfected mammalian cell clone. Rotary shadowing electron microscopy demonstrated a globular domain connected to a short rod-like segment of variable length. This suggested that tandem arrays of LA modules form rod-like elements. Folding into a native structure was indicated by the sharing of immunological epitopes with tissue perlecan, a CD spectrum demonstrating 37% beta structure and a limited susceptibility to proteolysis. The domain also showed N-glycosylation of a single acceptor site and 7-8 O-linked oligosaccharides. The latter were located mainly in the link region within proline-rich sequences. C1 MAX PLANCK INST BIOCHEM,D-82152 MARTINSRIED,GERMANY. NIDR,NIH,BETHESDA,MD 20892. RI Mann, Karlheinz/C-4254-2008 NR 31 TC 25 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 4 PY 1996 VL 396 IS 2-3 BP 127 EP 131 DI 10.1016/0014-5793(96)01082-4 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA VT127 UT WOS:A1996VT12700004 PM 8914972 ER PT J AU Herrmann, K AF Herrmann, K TI Differential distribution of AMPA receptors and glutamate during pre- and postnatal development in the visual cortex of ferrets SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE GluR1; GluR213; immunohistochemistry; cortical development; excitatory amino acid ID AMINO-ACID RECEPTORS; METHYL-D-ASPARTATE; DEVELOPING CEREBRAL-CORTEX; SOMATIC SENSORY CORTEX; CENTRAL-NERVOUS-SYSTEM; NMDA RECEPTORS; RAT-BRAIN; HIPPOCAMPAL-NEURONS; CORTICAL-NEURONS; TRANSIENT EXPRESSION AB Immunohistochemical methods were used to study the distribution and time-course of appearance of cells expressing glutamate and alpha-amino-3-hydroxy-5-methyl-4-isoaxazole propionic acid (AMPA)-type glutamate receptors (GluR1 and GluR2/3) during development of the ferret visual cortex. Glutamate is present in many neurons in the ventricular zone, intermediate zone, developing cortical plate, and marginal zone as early as embryonic day (E) 34 (birth is at E41 in ferrets). Glutamate attains its adult distribution coincident with the completion of cellular migration. By contrast, GluR1 immunoreactivity emerges more slowly. By birth, GluR1 immunoreactivity is present only in a few neurons in the marginal zone and ventricular zone but is abundant in the marginal zone and subplate, where synaptogenesis commences. The number and staining intensity of GluR1-positive cells increases dramatically during the first two postnatal weeks and is maximal between the second and third week, before slowly declining to adult levels. Cortical cells immunopositive for GluR2/3 follow a similar pattern, although their distribution differs: GluR2/3-positive cells are mainly pyramidal cells. During the first postnatal week, GluR2/3 is also transiently present in fibers in the intermediate zone, which at this stage contains many thalamocortical and callosal and corticofugal axons. The abundance of glutamate at fetal stages, especially in the ventricular zone, is consistent with the previously proposed role of glutamate in mediating trophic effects in vivo, as previously demonstrated in vitro. The expression of AMPA receptors, as well as their transient overexpression, confirms the results of in situ hybridization studies and may imply a developmental role in neuronal differentiation for these receptors, in addition to their mature role in mediating cortical transmission. (C) 1996 Wiley-Liss, Inc. RP Herrmann, K (reprint author), NIMH,NIHAC,NEUROPHYSIOL LAB,POB 608,POOLESVILLE,MD 20837, USA. NR 97 TC 24 Z9 24 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD NOV 4 PY 1996 VL 375 IS 1 BP 1 EP 17 PG 17 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA VQ287 UT WOS:A1996VQ28700001 PM 8913890 ER PT J AU Wong, ML Bongiorno, PB AlShekhlee, A Esposito, A Khatri, P Licinio, J AF Wong, ML Bongiorno, PB AlShekhlee, A Esposito, A Khatri, P Licinio, J TI IL-1 beta, IL-1 receptor type I and iNOS gene expression in rat brain vasculature and perivascular areas SO NEUROREPORT LA English DT Article DE brain vasculature; in situ hybridization interleukin-1; interleukin-1 receptors; lipopolysaccharide; nitric oxide; nitric oxide synthase; sepsis ID NITRIC-OXIDE SYNTHASE; INTERLEUKIN-1 RECEPTOR; MESSENGER-RNA; PITUITARY; LOCALIZATION; HYPOTHALAMUS; VASOPRESSIN; ANTAGONIST; CLONING; RELEASE AB THE mechanism by which IL-1 beta exerts its actions in the brain during systemic inflammation is not fully understood, as neither IL-1 receptor gene expression nor IL-1 binding have been identified in significant levels in key areas that respond to IL-1 beta. Having hypothesized that perivascular nitric oxide (NO) might modulate the effects of systemic IL-1 beta in the brain, we studied the expression of the genes encoding for IL-1 beta, the signal-transducing IL-1 receptor type I (IL-1RI) and inducible NO synthase (iNOS) constitutively and during systemic inflammation in vascular and perivascular regions of the rat brain. Our results show that IL-1RI is constitutively expressed at the interface of the vascular wall and perivascular glia. During systemic inflammation there is induction of IL-1 beta gene expression in the vascular wall, accompanied by perivascular induction of iNOS mRNA. We conclude that during systemic inflammation vascular IL-1 beta, binding to vascular and perivascular IL-1RI receptors, may induce perivascular iNOS gene expression, leading to the production of NO and modulation of the effects of IL-1 beta in the brain. We propose that the vascular and perivascular induction of iNOS mRNA by IL-1 beta might represent a mechanism for the modulation of the central nervous system effects of peripheral inflammatory mediators. RP Wong, ML (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,INTRAMURAL RES PROGRAM,NIH,BLDG 10,RM 3S231,10 CTR DR MSC 1284,BETHESDA,MD 20892, USA. RI Wong, Ma-Li/D-7903-2011; Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 24 TC 52 Z9 55 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD NOV 4 PY 1996 VL 7 IS 15-17 BP 2445 EP 2448 DI 10.1097/00001756-199611040-00008 PG 4 WC Neurosciences SC Neurosciences & Neurology GA WB711 UT WOS:A1996WB71100008 PM 8981400 ER PT J AU Bendotti, C Pende, M Guglielmetti, F Samanin, R AF Bendotti, C Pende, M Guglielmetti, F Samanin, R TI Cycloheximide inhibits kainic acid-induced GAP-43 mRNA in dentate granule cells in rats SO NEUROREPORT LA English DT Article DE GAP-43; sprouting; dentate mossy fibres; hippocampus; epilepsy; kainic acid; in situ hybridization; cycloheximide ID FACTOR MESSENGER-RNA; IN-SITU HYBRIDIZATION; INDUCED SEIZURES; MOSSY FIBERS; BRAIN; EXPRESSION; HIPPOCAMPUS; PLASTICITY; NEURONS; DAMAGE AB WE have previously shown that kainic acid-induced seizures in adult rats caused an up-regulation of GAP-43 mRNA in the granule cells of the hippocampus, suggesting an involvement of this protein in the kainic acid-induced sprouting of messy fibres. To determine whether this effect was dependent on the synthesis of proteins activated under these experimental conditions we examined the effect of cycloheximide, a protein synthesis inhibitor, on kainic acid-induced GAP-43 mRNA. Cycloheximide, injected s.c. 2 h but not 8 h after kainic acid, markedly reduced the increased expression of GAP-43 mRNA in granule cells. These results suggest that a rapid mechanism involving new protein synthesis is activated by kainic acid to induce GAP-43 in the granule cells and possibly trigger the structural remodeling of messy fibres. C1 NICHHD, NIH, BETHESDA, MD 20892 USA. RP MARIO NEGRI INST PHARMACOL RES, NEUROPHARMACOL LAB, VIA ERITREA 62, I-20157 MILAN, ITALY. NR 25 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0959-4965 EI 1473-558X J9 NEUROREPORT JI Neuroreport PD NOV 4 PY 1996 VL 7 IS 15-17 BP 2539 EP 2542 DI 10.1097/00001756-199611040-00027 PG 4 WC Neurosciences SC Neurosciences & Neurology GA WB711 UT WOS:A1996WB71100027 PM 8981419 ER PT J AU Feinberg, MB AF Feinberg, MB TI Lessons from and about AIDS ... SO LANCET LA English DT Editorial Material RP Feinberg, MB (reprint author), NIH,OFF AIDS RES,BETHESDA,MD 20892, USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD NOV 2 PY 1996 VL 348 IS 9036 BP 1188 EP 1188 DI 10.1016/S0140-6736(05)65479-7 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VQ467 UT WOS:A1996VQ46700007 PM 8898034 ER PT J AU Clarke, M Collins, R Davies, C Godwin, J Gray, R Peto, R Abe, O Abe, R Enomoto, K Kikuchi, K Koyama, H Nomura, Y Sakai, K Sugimachi, K Tominaga, T Uchino, J Yoshida, M vandeVelde, AO vanDongen, JA Vermorken, JB Arvelakis, A Giokas, G Lissaios, B Harvey, VJ Holdaway, TM Kay, RG Mason, BH Coates, A Forbes, JF Focan, C Lobelle, JP Peek, U Oates, GD Powell, J Bastert, G Rauschecker, H Sauer, R Sauerbrei, W Schauer, A Schumacher, M Durand, M Mauriac, L Bartholomeus, S Piccart, MJ Gelman, RS Henderson, IC Shapiro, CL Hancock, AK Masood, MB Parker, D Price, JJ Jackson, S Ragaz, J Delozier, T MaceLesech, J Haybittle, JL Cirrincione, C Korzun, A Weiss, RB Wood, WC Baum, M Houghton, J Riley, D Dent, DM Gudgeon, CA Hacking, A Horgan, K Hughes, L Stewart, HJ Gordon, NH Davis, HL Lehingue, Y Owen, JR Meier, P Howell, A Ribeiro, GC Swindell, R Albano, J deOliveira, CF Gervasio, H Gordilho, J Carstensen, B Palshof, T Johansen, H Korzeniowski, S Skolyszewski, J Andersen, KW Axelsson, CK BlichertToft, M Mouridsen, HT Overgaard, M Rose, C Corcoran, N Trampisch, HJ Abeloff, MD Carbone, PC Glick, J Tormey, DC Rossbach, J Scanlon, EF Schurman, S deSchryver, A Yosef, HMA McArdle, CS Smith, DC Lara, PC Boccardo, F Erazo, A Medina, JY Izuo, M Morishita, Y Bentley, A Doran, Z Fentiman, IS Hayward, JL Rubens, RD Kaufmann, M Jonat, W Scheurlen, H vonFournier, D Fountzilas, G Klefstrom, P Blomqvist, C Cuzick, J Margreiter, R Castiglione, M Cavalli, F Collins, J Forbes, J Gelber, RD Goldhirsch, A Lindtner, J Price, KN Rudenstam, CM Senn, HJ Bliss, JM Chilvers, CED Coombes, RC Marty, M Borovik, R Brufman, G Hayat, H Robinson, E Wigler, N Pannuti, F Takashima, S Tasutomi, T Sonoo, H Yamashita, J Ogawa, M Hupperets, PSGJ Bonte, J Tengrup, I TennvallNittby, L Martin, P Romain, S Ahmann, D Schaid, DJ Buzdar, AU Smith, T Hakes, T Norton, L Wittes, R delaHuerta, R Sainz, MG Bonadonna, G delVecchio, M Valagussa, P Veronesi, U Dubois, JB Bianco, AR Lippman, ME Pierce, LJ Simon, R Steinberg, SM Brown, A Fisher, B Redmond, C Wolmark, N Jackson, IM Palmer, MK Ingle, JN Suman, VJ Bengtsson, NO Larsson, LG Lythgoe, JP Kissin, M Hannisdal, E Varhaug, JE NissenMeyer, R Blamey, RW Mitchell, AK Robertson, JFR Nakamura, Y Mathe, G Misset, JL AbuZahra, HT Clarke, EA McLaughlin, JR Clark, RM Levine, M Myles, JD Pater, JL Pritchard, KI Morimoto, K Sawa, K Takatsuka, Y Gundersen, S HauerJensen, M Host, A Crossley, E Durrant, K Harris, A Beighton, A Collins, R Evans, V Greaves, E Harwood, C James, S Lau, E Mead, G Muldal, A Naughton, A Tooth, A Wheatley, K Rambert, P Asselain, B Salmon, RJ Vilcoq, JR Arriagada, R Hill, C Laplanche, A Le, MG Speilmann, M Cocconi, G diBlasio, B Catalano, R Creech, RH Brockschmidt, J Cooper, MR Andrysek, O Barkmanova, J Falkson, CJ Abraham, M Klijn, JGM TreurnietDonker, AD vanPutten, WLJ Easton, D Powles, TJ Gazet, JC Semiglazov, V Deshpande, N diMartino, L Douglas, P Host, H Bryant, AJS Ewing, GH KrushenKosloski, JL Forrest, APM Jack, W McDonald, C Moller, TR Ryden, S Carstensen, J Hatschek, T Soderberg, M Carpenter, JT Albain, K Crowley, J Green, S Martino, S Osborne, CK Ravdin, PM Rutqvist, LE Wallgren, A Holm, LE Yoshimoto, M DeBoer, G Paterson, AHG Meakin, JW Panzarella, T Naja, A Bahi, J Reid, M Spittle, M Senanayake, F Bergh, J Holmberg, L Sevelda, P Zielinsky, CC Jakesz, R Gnant, M Buchanan, RB Cross, M Dunn, JA Gillespie, WM Kelly, K Morrison, JM Litton, A Chlebowski, RT Bezwoda, WR Caffier, H AF Clarke, M Collins, R Davies, C Godwin, J Gray, R Peto, R Abe, O Abe, R Enomoto, K Kikuchi, K Koyama, H Nomura, Y Sakai, K Sugimachi, K Tominaga, T Uchino, J Yoshida, M vandeVelde, AO vanDongen, JA Vermorken, JB Arvelakis, A Giokas, G Lissaios, B Harvey, VJ Holdaway, TM Kay, RG Mason, BH Coates, A Forbes, JF Focan, C Lobelle, JP Peek, U Oates, GD Powell, J Bastert, G Rauschecker, H Sauer, R Sauerbrei, W Schauer, A Schumacher, M Durand, M Mauriac, L Bartholomeus, S Piccart, MJ Gelman, RS Henderson, IC Shapiro, CL Hancock, AK Masood, MB Parker, D Price, JJ Jackson, S Ragaz, J Delozier, T MaceLesech, J Haybittle, JL Cirrincione, C Korzun, A Weiss, RB Wood, WC Baum, M Houghton, J Riley, D Dent, DM Gudgeon, CA Hacking, A Horgan, K Hughes, L Stewart, HJ Gordon, NH Davis, HL Lehingue, Y Owen, JR Meier, P Howell, A Ribeiro, GC Swindell, R Albano, J deOliveira, CF Gervasio, H Gordilho, J Carstensen, B Palshof, T Johansen, H Korzeniowski, S Skolyszewski, J Andersen, KW Axelsson, CK BlichertToft, M Mouridsen, HT Overgaard, M Rose, C Corcoran, N Trampisch, HJ Abeloff, MD Carbone, PC Glick, J Tormey, DC Rossbach, J Scanlon, EF Schurman, S deSchryver, A Yosef, HMA McArdle, CS Smith, DC Lara, PC Boccardo, F Erazo, A Medina, JY Izuo, M Morishita, Y Bentley, A Doran, Z Fentiman, IS Hayward, JL Rubens, RD Kaufmann, M Jonat, W Scheurlen, H vonFournier, D Fountzilas, G Klefstrom, P Blomqvist, C Cuzick, J Margreiter, R Castiglione, M Cavalli, F Collins, J Forbes, J Gelber, RD Goldhirsch, A Lindtner, J Price, KN Rudenstam, CM Senn, HJ Bliss, JM Chilvers, CED Coombes, RC Marty, M Borovik, R Brufman, G Hayat, H Robinson, E Wigler, N Pannuti, F Takashima, S Tasutomi, T Sonoo, H Yamashita, J Ogawa, M Hupperets, PSGJ Bonte, J Tengrup, I TennvallNittby, L Martin, P Romain, S Ahmann, D Schaid, DJ Buzdar, AU Smith, T Hakes, T Norton, L Wittes, R delaHuerta, R Sainz, MG Bonadonna, G delVecchio, M Valagussa, P Veronesi, U Dubois, JB Bianco, AR Lippman, ME Pierce, LJ Simon, R Steinberg, SM Brown, A Fisher, B Redmond, C Wolmark, N Jackson, IM Palmer, MK Ingle, JN Suman, VJ Bengtsson, NO Larsson, LG Lythgoe, JP Kissin, M Hannisdal, E Varhaug, JE NissenMeyer, R Blamey, RW Mitchell, AK Robertson, JFR Nakamura, Y Mathe, G Misset, JL AbuZahra, HT Clarke, EA McLaughlin, JR Clark, RM Levine, M Myles, JD Pater, JL Pritchard, KI Morimoto, K Sawa, K Takatsuka, Y Gundersen, S HauerJensen, M Host, A Crossley, E Durrant, K Harris, A Beighton, A Collins, R Evans, V Greaves, E Harwood, C James, S Lau, E Mead, G Muldal, A Naughton, A Tooth, A Wheatley, K Rambert, P Asselain, B Salmon, RJ Vilcoq, JR Arriagada, R Hill, C Laplanche, A Le, MG Speilmann, M Cocconi, G diBlasio, B Catalano, R Creech, RH Brockschmidt, J Cooper, MR Andrysek, O Barkmanova, J Falkson, CJ Abraham, M Klijn, JGM TreurnietDonker, AD vanPutten, WLJ Easton, D Powles, TJ Gazet, JC Semiglazov, V Deshpande, N diMartino, L Douglas, P Host, H Bryant, AJS Ewing, GH KrushenKosloski, JL Forrest, APM Jack, W McDonald, C Moller, TR Ryden, S Carstensen, J Hatschek, T Soderberg, M Carpenter, JT Albain, K Crowley, J Green, S Martino, S Osborne, CK Ravdin, PM Rutqvist, LE Wallgren, A Holm, LE Yoshimoto, M DeBoer, G Paterson, AHG Meakin, JW Panzarella, T Naja, A Bahi, J Reid, M Spittle, M Senanayake, F Bergh, J Holmberg, L Sevelda, P Zielinsky, CC Jakesz, R Gnant, M Buchanan, RB Cross, M Dunn, JA Gillespie, WM Kelly, K Morrison, JM Litton, A Chlebowski, RT Bezwoda, WR Caffier, H TI Ovarian ablation in early breast cancer: Overview of the randomised trials SO LANCET LA English DT Article AB Background Among women with early breast cancer, the effects of ovarian ablation on recurrence and death have been assessed by several randomised trials that now have long follow-up. In this report, the Early Breast Cancer Trialists' Collaborative Group present their third 5-yearly systematic overview (meta-analysis), now with 15 years' follow-up. Methods in 1995, information was sought on each patient in any randomised trial of ovarian ablation or suppression versus control that began before 1990. Data were obtained for 12 of the 13 studies that assessed ovarian ablation by irradiation or surgery, all of which began before 1980, but not for the four studies that assessed ovarian suppression by drugs, all of which began after 1985. Menopausal status was not consistently defined across trials; therefore, the main analyses are limited to women aged under 50 (rather than ''premenopausal'') when randomised. Oestrogen receptors were measured only in the trials of ablation plus cytotoxic chemotherapy versus the same chemotherapy alone. Findings Among 2102 women aged under 50 when randomised, most of whom would have been premenopausal at diagnosis, 1130 deaths and an additional 153 recurrences were reported. 15-year survival was highly significantly improved among those allocated ovarian ablation (52 . 4 vs 46 . 1%, 6 . 3 [SD 2 . 3] fewer deaths per 100 women, logrank 2p=0 . 001), as was recurrence-free survival (45 . 0 vs 39 . 0%, 2p=0 . 0007). The numbers of events were too small for any subgroup analyses to be reliable. The benefit was, however, significant both for those with (''node positive'') and for those without (''node negative'') axillary spread when diagnosed. In the trials of ablation plus cytotoxic chemotherapy versus the same chemotherapy alone, the benefit appeared smaller (even for women with oestrogen receptors detected on the primary tumour) than in the trials of ablation in the absence of chemotherapy (where the observed survival improvements were about six per 100 node-negative women and 12 per 100 node-positive women). Among 1354 women aged 50 or over when randomised, most of whom would have been perimenopausal or postmenopausal, there was only a non-significant improvement in survival and recurrence-free survival. Interpretation In women aged under 50 with early breast cancer, ablation of functioning ovaries significantly improves long-term survival, at least in the absence of chemotherapy. Further randomised evidence is needed on the additional effects of ovarian ablation in the presence of other adjuvant treatments, and to assess the relevance of hormone-receptor measurements. C1 AMSTERDAM INTEGRAAL KANKERCTR, AMSTERDAM, NETHERLANDS. ATHENS METAXAS MEM CANC HOSP, ATHENS, GREECE. AUCKLAND BREAST CANC STUDY GRP, AUCKLAND, NEW ZEALAND. CARDIFF SURG TRIALISTS, CARDIFF, S GLAM, WALES. BERLIN BUCH AKAD WISSENSCH, BERLIN, GERMANY. BIRMINGHAM GEN HOSP, BIRMINGHAM, W MIDLANDS, ENGLAND. BMFT FREIBERG, FREIBERG, GERMANY. BORDEAUX INST BERGONIE, BORDEAUX, FRANCE. DANA FARBER CANC INST, BOSTON, MA 02115 USA. BRADFORD ROYAL INFIRM, BRADFORD BD9 6RJ, W YORKSHIRE, ENGLAND. BRITISH COLUMBIA CANC AGCY, VANCOUVER, BC V5Z 4E6, CANADA. CAEN CTR REG FRANCOIS BACLESSE, CAEN, FRANCE. ADDENBROOKES HOSP, CAMBRIDGE, ENGLAND. CANC & LEUKEMIA GRP B, DURHAM, NC USA. CANC RES CAMPAIGN, LONDON SW1Y 5AR, ENGLAND. GROOTE SCHUUR HOSP, ZA-7925 CAPE TOWN, SOUTH AFRICA. CASE WESTERN RESERVE UNIV, CLEVELAND, OH 44106 USA. CTR LEON BERARD, F-69373 LYON, FRANCE. CHELTENHAM GEN HOSP, CHELTENHAM, GLOS, ENGLAND. UNIV CHICAGO, CHICAGO, IL 60637 USA. CHRISTIE HOSP & HOLT RADIUM INST, MANCHESTER M20 9BX, LANCS, ENGLAND. COIMBRA INST ONCOL, COIMBRA, PORTUGAL. DANISH CANC REGISTRY, COPENHAGEN, DENMARK. COPENHAGEN RADIUM CTR, COPENHAGEN, DENMARK. CRACOW INST ONCOL, KRAKOW, POLAND. ST LUKES HOSP, DUBLIN, IRELAND. UNIV DUSSELDORF, D-4000 DUSSELDORF, GERMANY. EASTERN COOPERAT ONCOL GRP, BOSTON, MA USA. EUROPEAN ORG RES TREATMENT CANC, BRUSSELS, BELGIUM. NORTHWESTERN UNIV, EVANSTON HOSP, EVANSTON, IL 60201 USA. STATE UNIV GHENT HOSP, B-9000 GHENT, BELGIUM. WESTERN INFIRM & ASSOCIATED HOSP, BEATSON ONCOL CTR, GLASGOW G11 6NT, LANARK, SCOTLAND. GLASGOW VICTORIA INFIRM, GLASGOW, LANARK, SCOTLAND. GRANADA UNIV HOSP, GRANADA, SPAIN. GUADALAJARA HOSP 20 NOVIEMBRE, GUADALAJARA, JALISCO, MEXICO. GUNMA UNIV, MAEBASHI, GUMMA 371, JAPAN. GUYS HOSP, LONDON SE1 9RT, ENGLAND. HEIDELBERG UNIV 1, HEIDELBERG, GERMANY. HEIDELBERG UNIV 2, HEIDELBERG, GERMANY. HELLENIC COOPERAT ONCOL GRP, ATHENS, GREECE. HELSINKI DEACONESS MED CTR, HELSINKI, FINLAND. UNIV HELSINKI, FIN-00014 HELSINKI, FINLAND. IMPERIAL CANC RES FUND, LONDON WC2A 3PX, ENGLAND. UNIV INNSBRUCK, A-6020 INNSBRUCK, AUSTRIA. LUDWIG INT BREAST CANC STUDY GRP, EPALINGES, SWITZERLAND. INT COLLABORAT CANC GRP, LONDON, ENGLAND. ISRAEL NSABC, JERUSALEM, ISRAEL. KAWASAKI MED UNIV, KAWASAKI, KANAGAWA, JAPAN. KUMAMOTO UNIV GRP, KUMAMOTO, JAPAN. KYUSHU NATL CANC CTR, FUKUOKA, JAPAN. BREAST CANC STUDY GRP COMPREHENS CANC CTR, LIMBURG, NETHERLANDS. ACAD ZIEKENHUIS ST RAFAEL, LOUVAIN, BELGIUM. MARSEILLE LAB CANCEROL BIOL APM, MARSEILLE, FRANCE. MAYO CLIN, ROCHESTER, MN 55905 USA. UNIV TEXAS, MD ANDERSON CANC CTR, HOUSTON, TX USA. MEXICAN NATL MED CTR, MEXICO CITY, DF, MEXICO. IST NAZL STUDIO & CURA TUMORI, I-20133 MILAN, ITALY. CTR PAUL LAMARQUE, MONTPELLIER, FRANCE. UNIV NAPLES, I-80138 NAPLES, ITALY. NCI, BETHESDA, MD 20892 USA. NORTHWICK PK HOSP & CLIN RES CTR, HARROW HA1 3UJ, MIDDX, ENGLAND. NORWEGIAN RADIUM HOSP, OSLO, NORWAY. CITY HOSP NOTTINGHAM, NOTTINGHAM, ENGLAND. OITA PREFECTURAL HOSP, OITA, JAPAN. ONTARIO CANC TREATMENT & RES FDN, TORONTO, ON, CANADA. ONTARIO CLIN ONCOL GRP, HAMILTON, ON, CANADA. CANADA CLIN TRIALS GRP, ONTARIO NATL CANC INST, KINGSTON, ON, CANADA. OSAKA CITY UNIV, OSAKA 558, JAPAN. OSAKA NATL HOSP, OSAKA, JAPAN. OSLO RADIUM HOSP, OSLO, NORWAY. OXFORD CHURCHILL HOSP, OXFORD, ENGLAND. OXFORD ICRF MRC CLIN TRIAL SERV UNIT, OXFORD, ENGLAND. CTR RENE HUGUENIN, PARIS, FRANCE. INST CURIE, PARIS, FRANCE. INST GUSTAVE ROUSSY, PARIS, FRANCE. PARMA HOSP, PARMA, ITALY. FOX CHASE CANC CTR, PHILADELPHIA, PA 19111 USA. PIEDMONT ONCOL ASSOC, WINSTON SALEM, NC USA. CHARLES UNIV, PRAGUE, CZECH REPUBLIC. UNIV PRETORIA, ZA-0002 PRETORIA, SOUTH AFRICA. INST CARDIOVASC ROSARIO, ROSARIO, ARGENTINA. DR DANIEL DEN HOED CANC CTR, NL-3008 AE ROTTERDAM, NETHERLANDS. ROYAL MARSDEN HOSP, CANC RES INST, LONDON, ENGLAND. UNIV LONDON ST GEORGES HOSP, LONDON SW17 0RE, ENGLAND. ST PETERSBURG PETROV RES INST ONCOL, ST PETERSBURG, RUSSIA. SARDINIA ONCOL HOSP A BUSINICO, SARDINIA, ITALY. SASKATCHEWAN CANC FDN, SASKATOON, SK, CANADA. SCOTTISH CANC TRIALS OFF, EDINBURGH, MIDLOTHIAN, SCOTLAND. SW ONCOL GRP, KANSAS CITY, KS USA. STOCKHOLM BREAST CANC STUDY GRP, STOCKHOLM, SWEDEN. KAROLINSKA HOSP, S-10401 STOCKHOLM, SWEDEN. SAKK & OSAKO, SWISS GRP CLIN CANC RES, BERN, SWITZERLAND. TEL AVIV UNIV, IL-69978 TEL AVIV, ISRAEL. CANC INST HOSP, TOKYO, JAPAN. TORONTO EDMONTON BREAST CANC STUDY GRP, TORONTO, ON, CANADA. PRINCESS MARGARET HOSP, TORONTO, ON M4X 1K9, CANADA. CTR CLAUDIUS REGAUD, TOULOUSE, FRANCE. INST SALAH AZAIZ, TUNIS, TUNISIA. UPPSALA OREBRO CANC STUDY GRP, UPPSALA, SWEDEN. UNIV HOSP VIENNA, DEPT GYNAECOL 1, VIENNA, AUSTRIA. UNIV HOSP VIENNA, DEPT SURG, VIENNA, AUSTRIA. UNIV WITWATERSRAND, ZA-2050 WITWATERSRAND, SOUTH AFRICA. UNIV WURZBURG, D-97070 WURZBURG, GERMANY. RP Clarke, M (reprint author), RADCLIFFE INFIRM, CLIN TRIAL SERV UNIT, OXFORD OX2 6HE, ENGLAND. RI Jonat, Walter/E-3024-2010; McLaughlin, John/E-4577-2013; Barkmanova, Jaroslava/A-1411-2017 OI Barkmanova, Jaroslava/0000-0003-1406-7292 NR 17 TC 352 Z9 357 U1 1 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD NOV 2 PY 1996 VL 348 IS 9036 BP 1189 EP 1196 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA VQ467 UT WOS:A1996VQ46700009 ER PT J AU Schneerson, R Robbins, JB AF Schneerson, R Robbins, JB TI Ukraine's diphtheria campaign - Reply SO LANCET LA English DT Letter RP Schneerson, R (reprint author), NICHHD,DEV & MOL IMMUN LAB,NIH,BETHESDA,MD 20893, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD NOV 2 PY 1996 VL 348 IS 9036 BP 1245 EP 1245 DI 10.1016/S0140-6736(05)65522-5 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VQ467 UT WOS:A1996VQ46700056 PM 8898058 ER PT J AU Murray, M Fleming, M AF Murray, M Fleming, M TI Prevention and treatment of alcohol-related problems: An international medical education model SO ACADEMIC MEDICINE LA English DT Article ID COLLABORATIVE PROJECT; CONSUMPTION; IDENTIFICATION; INTERVENTION; DRINKING AB Alcohol abuse and alcoholism are among the world's most pressing public health concerns. Research has shown that while primary care physicians are in a good position to screen for alcohol-use disorders and to aid in treating these problems, they tend to identify only a small percentage of patients with such disorders and they rarely intervene with these persons. This situation is probably attributable to the fact that medical students worldwide are taught very little about alcohol-related problems. Clearly there is an urgent need to educate the world's doctors about preventing, diagnosing, and treating alcohol abuse and addiction. In this paper, the authors describe a model international program for educating physicians about alcohol-related problems that was developed by the National Institute on Alcohol Abuse and,alcoholism (NIAAA) in cooperation with the Center for Addiction Research and Education (CARE) at the University of Wisconsin-Madison. They describe the components of the initiative's ''trainer-development'' approach and critical issues in implementing the program in other countries. Finally, they discuss how the program was successfully implemented in Poland and describe the NIAAA's plans for introducing the model in several other countries. C1 UNIV WISCONSIN,MADISON,WI. POLISH MINIST HLTH PREVENT ALCOHOL RELATED PROBLE,WARSAW,POLAND. RP Murray, M (reprint author), NIAAA,INT RES & TRAINING PROGRAM,6000 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 26 TC 9 Z9 14 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD NOV PY 1996 VL 71 IS 11 BP 1204 EP 1210 DI 10.1097/00001888-199611000-00017 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA VT717 UT WOS:A1996VT71700020 PM 9217509 ER PT J AU Jaskolski, M Wlodawer, A AF Jaskolski, M Wlodawer, A TI A minimalist's approach to the phase problem - Phasing selenomethionyl protein structures using Cu K alpha data SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID MACROMOLECULAR STRUCTURES; ANOMALOUS DIFFRACTION; RESOLUTION; REFINEMENT; MODELS AB The feasibility of phasing protein structures through the use of the isomorphous and anomalous signal of selenomethionyl (Se-Met) derivative and diffraction data collected with a standard laboratory CuK alpha X-ray source has been investigated. Interpretable electron-density maps were obtained for the core domain of avian sarcoma virus integrase, a typical medium-sized protein having four Met residues in a sequence of 156 amino acids. The r.m.s. difference between 3.1 Angstrom experimental phases obtained from Se-Met CuK alpha data and the final phases calculated from the refined model is 55 degrees. A procedure combining single isomorphous replacement/single anomalous scattering phasing and solvent flattening for data based on a single Se-Met derivative and CuK alpha radiation has been tested on this and another protein. The results are encouraging enough to indicate that such procedures might be recommended when a synchrotron source is not readily available. C1 POLISH ACAD SCI,INST BIOORGAN CHEM,CTR BIOCRYSTALLOG,POZNAN,POLAND. ADAM MICKIEWICZ UNIV POZNAN,FAC CHEM,DEPT CRYSTALLOG,POZNAN,POLAND. RP Jaskolski, M (reprint author), NCI,FREDERICK CANC RES & DEV CTR,MACROMOL STRUCT LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702, USA. NR 26 TC 5 Z9 5 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD NOV 1 PY 1996 VL 52 BP 1075 EP 1081 DI 10.1107/S0907444996008402 PN 6 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA VW616 UT WOS:A1996VW61600004 PM 15299566 ER PT J AU Bibbo, M Abati, A AF Bibbo, M Abati, A TI The uniform approach to breast fine needle aspiration biopsy SO ACTA CYTOLOGICA LA English DT Editorial Material DE breast neoplasms; breast diseases; aspiration biopsy; nomenclature C1 NCI,CYTOPATHOL SECT,NIH,BETHESDA,MD 20892. RP Bibbo, M (reprint author), THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DIV CYTOPATHOL,PHILADELPHIA,PA 19107, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD NOV-DEC PY 1996 VL 40 IS 6 BP 1119 EP 1119 PG 1 WC Pathology SC Pathology GA VY541 UT WOS:A1996VY54100001 ER PT J AU Abati, A Abele, J Bacus, SS Bedrossian, C Beerline, D Bibbo, M Cady, B Covell, J Davey, D Dawson, A Fornage, B Foster, R Frable, W Goldfischer, M Grohs, H Henry, M Hijazi, Y Hindle, W Howell, L Kaminsky, D Katz, R Kline, T Koss, LG Lannin, DR Layfield, L Leiman, G Lewis, M Lindholm, K Ljung, BM Masood, S Miyazaki, J Newstead, G OShaughnessy, J Page, D Powers, C Rollins, S Rosenthal, D Sanchez, MA Schmidt, W Sidawy, M Silverman, J Sneige, N Stahl, RE Stanley, M Thomas, P Vazquez, M Waisman, J Wolman, S Wunderlich, C Yawn, B AF Abati, A Abele, J Bacus, SS Bedrossian, C Beerline, D Bibbo, M Cady, B Covell, J Davey, D Dawson, A Fornage, B Foster, R Frable, W Goldfischer, M Grohs, H Henry, M Hijazi, Y Hindle, W Howell, L Kaminsky, D Katz, R Kline, T Koss, LG Lannin, DR Layfield, L Leiman, G Lewis, M Lindholm, K Ljung, BM Masood, S Miyazaki, J Newstead, G OShaughnessy, J Page, D Powers, C Rollins, S Rosenthal, D Sanchez, MA Schmidt, W Sidawy, M Silverman, J Sneige, N Stahl, RE Stanley, M Thomas, P Vazquez, M Waisman, J Wolman, S Wunderlich, C Yawn, B TI The uniform approach to breast fine needle aspiration biopsy - A synopsis SO ACTA CYTOLOGICA LA English DT Article; Proceedings Paper CT National-Cancer-Institute Conference CY SEP 09-10, 1996 CL BETHESDA, MD SP NCI RP Abati, A (reprint author), NCI,CYTOPATHOL SECT,NIH,BLDG 10,ROOM 2A19,10 CTR DR,MSC 1500,BETHESDA,MD 20892, USA. RI Thomas, Patricia/F-9978-2013 OI Thomas, Patricia/0000-0002-9390-3676 NR 0 TC 34 Z9 34 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD NOV-DEC PY 1996 VL 40 IS 6 BP 1120 EP 1126 PG 7 WC Pathology SC Pathology GA VY541 UT WOS:A1996VY54100002 ER PT J AU Dawson, DA AF Dawson, DA TI Temporal drinking patterns and variation in social consequences SO ADDICTION LA English DT Article; Proceedings Paper CT Conference on Social and Health Effects of Different Drinking Patterns CY NOV 13-17, 1995 CL TORONTO, CANADA SP Addict Res Fdn ID DAILY ALCOHOL-CONSUMPTION; ETHANOL; BOSTON AB Temporal drinking patterns and their associated social consequences are described for a sample of US adults aged 18 years and over who drank at least 12 drinks in the preceding year and did not restrict their drinking to special occasions (n = 16 086). The earliest time of day when these current regular drinkers reported usually drinking was between 6 a. m. and 11 a.m. for 1.2%, between II a. m. and 3 p. m. for 7.3%, between 3 p.m. and 6 p.m. for 31.2%, and after 6 p.m. for 60.3%. Less than one-tenth (7.7%) reported arty drinking (not necessarily their earliest drinking) between midnight and 6 a. m. Characteristics associated with above-average rates of both early (6 a. m.-3 p. m.) and late-night (midnight-6 a. m.) drinking included male gender, black race, low education and income and heavy quantity of ethanol intake per drinking day. Early drinking was also characteristic of the elderly and daily drinkers. Prior to adjusting for background variables and quantity and frequency of intake, early drinking was associated with a two- to nine-fold increase in the risk of alcohol-related interpersonal problems, hazardous use, job/school problems and legal problems, and lace-night drinking was associated with a three- to eight-fold increase in their prevalence. After adjusting for these factors in multiple logistic regression models, early drinking was associated with a 54% increase in the odds of interpersonal problems, a 39% increase in the odds of hazardous use and a 52% increase in the odds of legal problems. The association between early drinking and job/school problems fell just short of statistical significance. After adjusting for other factors, late-night drinking retained a significant association with all of the outcomes except legal problems. The magnitude of its association was greater than that of early drinking but varied substantially (i.e. interacted) with quantity of intake, race, ethnicity and gender. RP Dawson, DA (reprint author), NIAAA,DBE,WILLCO BLDG SUITE 514,6000 EXECUT BLVD,MSC 7003,BETHESDA,MD 20892, USA. NR 33 TC 23 Z9 24 U1 0 U2 0 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD NOV PY 1996 VL 91 IS 11 BP 1623 EP 1635 PG 13 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA VU389 UT WOS:A1996VU38900004 PM 8972921 ER PT J AU Johanson, CE Duffy, FF Anthony, JC AF Johanson, CE Duffy, FF Anthony, JC TI Associations between drug use and behavioral repertoire in urban youths (vol 91, pg 528, 1996) SO ADDICTION LA English DT Correction, Addition C1 NIDA,INTRAMURAL RES PROGRAM,ETIOL BRANCH,BALTIMORE,MD. NR 1 TC 1 Z9 1 U1 1 U2 1 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD NOV PY 1996 VL 91 IS 11 BP 1731 EP 1733 PG 3 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA VU389 UT WOS:A1996VU38900015 ER PT J AU Pollitt, FA Notgrass, CM Windle, C AF Pollitt, FA Notgrass, CM Windle, C TI Peer review of rural research grant applications SO ADMINISTRATION AND POLICY IN MENTAL HEALTH LA English DT Article C1 VANDERBILT UNIV,DEPT PSYCHOL,NASHVILLE,TN 37240. RP Pollitt, FA (reprint author), NIMH,OFF RURAL MENTAL HLTH RES,5600 FISHERS LANE,ROOM 10-104,ROCKVILLE,MD 20857, USA. NR 8 TC 0 Z9 0 U1 1 U2 1 PU HUMAN SCI PRESS INC PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 SN 0894-587X J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD NOV PY 1996 VL 24 IS 2 BP 173 EP 180 DI 10.1007/BF02042489 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA WA205 UT WOS:A1996WA20500007 ER PT J AU Lane, HC AF Lane, HC TI Has immunotherapy come of age? SO AIDS LA English DT Meeting Abstract C1 NIAID,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD NOV PY 1996 VL 10 SU 2 BP 11 EP 11 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA VU963 UT WOS:A1996VU96300001 ER PT J AU Schnittman, SM AF Schnittman, SM TI Antiretroviral therapy state-of-the-art: Review and recommendations SO AIDS LA English DT Meeting Abstract C1 NIAID,NIH,DIV AIDS,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD NOV PY 1996 VL 10 SU 2 BP 21 EP 21 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA VU963 UT WOS:A1996VU96300003 ER PT J AU Derouin, F Leport, C Pueyo, S Morlat, P Ecobichon, JL Letrillart, B Chene, G Luft, B Aubertin, J Hafner, R Vilde, JL Salamon, R AF Derouin, F Leport, C Pueyo, S Morlat, P Ecobichon, JL Letrillart, B Chene, G Luft, B Aubertin, J Hafner, R Vilde, JL Salamon, R TI Predictive value of Toxoplasma gondii antibody titres on the occurrence of toxoplasmic encephalitis in HIV-infected patients SO AIDS LA English DT Article DE HIV infection; toxoplasmic encephalitis; Toxoplasma serology; predictive factors ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; PREVALENCE; SEROLOGY; AIDS; RISK AB Objective: To study the predictive value of anti-Toxoplasma gondii antibody titres for the occurrence of toxoplasmic encephalitis (TE) in HIV-infected patients. Methods: Data from the placebo arm of a trial of primary prophylaxis for TE (ANRS 005/ACTG 154) were analysed. Patients included had CD4+ cell counts < 200x10(6)/l and a positive Toxoplasma serology. Immunoglobulin (Ig) G and IgM Toxoplasma antibody titres at entry were retrospectively determined by enzyme-linked immunosorbent assay and agglutination on serum samples in a single laboratory. Incidence of TE was estimated by Kaplan-Meier method and a Cox model was used to study the predictive value of antibody titres, adjusted for other covariates. Results: All 164 patients studied were positive for Ige antibodies and one had IgM antibodies. After a mean follow-up of 16 months, 31 cases of TE were documented. One-year incidence of TE was significantly higher in patients with Ige titres greater than or equal to 150 lU/ml (23.7%) than in patients with titres < 150 lU/ml (7.7%; relative risk, 3.1; P < 0.003). IgG titres remained significantly associated with the occurrence of TE (relative risk, 3.3; P < 0.005) in the Cox model. Predictive value of [ge titres did not differ according to baseline CD4+ cell counts. Conclusion: In patients with CD4+ cell counts < 200x10(6)/l, lge anti-Toxoplasma antibody titre is a prognostic factor of occurrence of TE, with a higher risk for titres greater than or equal to 150 IU/ml. This finding should reinforce the recommendation of specific prophylaxis in these patients. C1 HOP ST LOUIS,PARASITOL LAB,F-75475 PARIS 10,FRANCE. HOP CLAUDE BERNARD,DEPT INFECT & TROP MED,PARIS,FRANCE. U330 INSERM,BORDEAUX,FRANCE. CENT HOSP,BORDEAUX,FRANCE. UNIV BORDEAUX,BORDEAUX,FRANCE. SUNY STONY BROOK,STONY BROOK,NY 11794. NIAID,DIV AIDS,BETHESDA,MD 20892. RI chene, genevieve/H-8665-2014; OI Luft, Benjamin/0000-0001-9008-7004 NR 20 TC 43 Z9 46 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD NOV PY 1996 VL 10 IS 13 BP 1521 EP 1527 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA VR234 UT WOS:A1996VR23400010 PM 8931787 ER PT J AU Chou, SP Grant, BF Dawson, DA AF Chou, SP Grant, BF Dawson, DA TI Medical consequences of alcohol consumption - United States, 1992 SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol; alcohol-related morbidity; benefits of drinking; prevalence ID CORONARY HEART-DISEASE; U-SHAPED CURVE; LIVER-DISEASE; MORTALITY; MODERATE; ETHANOL; RISK; POPULATION; WINE AB There is plenty of evidence in the alcohol literature that chronic excessive use of alcohol poses a threat to every organ system in the body. At the same time, there is a growing consensus that drinking in moderation protects against cardiovascular disease. This study was based on the most recent national household survey of the United States general population on drinking practices, alcohol use disorders, and their associated disabilities. The prevalences of major alcohol-related diseases were examined across different categories of drinking status. Excess morbidity caused by heavy intake of alcohol was also studied. Results were generally in agreement with the popular belief that light or moderate drinking is beneficial relative to abstention, particularly that moderate alcohol consumption confers a beneficial cardiovascular effect. Our findings also pointed toward the injurious effect of heavy alcohol use. However, results on benefits of drinking must be interpreted with caution. RP Chou, SP (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,SUITE 514,6000 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 56 TC 32 Z9 32 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 1996 VL 20 IS 8 BP 1423 EP 1429 DI 10.1111/j.1530-0277.1996.tb01144.x PG 7 WC Substance Abuse SC Substance Abuse GA VU644 UT WOS:A1996VU64400016 PM 8947320 ER PT J AU Johnson, EO vandenBree, MBM Pickens, RW AF Johnson, EO vandenBree, MBM Pickens, RW TI Subtypes of alcohol-dependent men: A typology based on relative genetic and environmental loading SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE typology; alcoholism; genetics; subtypes; males ID HEALTH INTERVIEW SURVEY; PLATELET MAO ACTIVITY; SUBGROUPING ALCOHOLICS; ANTISOCIAL PERSONALITY; FAMILIAL TRANSMISSION; II ALCOHOLISM; CRITERIA; ABUSE; HETEROGENEITY; INHERITANCE AB Using scales that distinguish between relative genetic and environmental loading, cluster analysis was used to identify three subtypes of alcohol dependence in Caucasian men from the Epidemiologic Catchment Area study (n = 911). Although all subjects met DSM-III criteria for alcohol dependence, only the severe subtype showed evidence of substantial genetic influence, When compared on a range of clinical characteristics, the mild subtype (53% of the sample) was typically least adversely affected and the severe subtype (17%) most affected, with the dyssocial subtype (30%) falling between. Severe subtype subjects had significantly greater comorbid drug dependence and were at least four times more likely than mild subjects to have sought treatment for alcohol problems, Ratio of genetic scale score to total symptom count (genetic ratio) was highest for the severe subtype (mean = 0.37), and negatively correlated with age of first alcohol problem (r(s) = -0.16) and years between first intoxication and first problem (r(s) = -0.19). No significant correlations were found between these clinical features and genetic ratio for the mild or dyssocial subtypes. Use of these scales and subtypes may improve our ability to detect specific gene effects in genetic linkage studies and to identify environmental influences in behavioral and epidemiological studies. RP Johnson, EO (reprint author), NIDA,ADDICT RES CTR,INTRAMURAL RES PROGRAM,POB 5180,BALTIMORE,MD 21224, USA. NR 56 TC 37 Z9 37 U1 4 U2 6 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 1996 VL 20 IS 8 BP 1472 EP 1480 DI 10.1111/j.1530-0277.1996.tb01151.x PG 9 WC Substance Abuse SC Substance Abuse GA VU644 UT WOS:A1996VU64400023 PM 8947327 ER PT J AU Grant, BF AF Grant, BF TI DSM-IV, DSM-III-R, and ICD-10 alcohol and drug abuse/harmful use and dependence, United States, 1992: A nosological comparison SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article ID RELIABILITY; INTERVIEW AB This study assessed agreement between DSM-IV, DSM-III-R, and ICD-10 diagnoses of alcohol and drug use disorders using data from a large representative sample of the United States population, Agreement between the three diagnostic systems for dependence was good to excellent for past year, prior to the past year, and lifetime diagnoses, for both genders, each ethnic group, and younger and older respondents, Cross-system comparisons between DSM-IV and DSM-III-R abuse were good to excellent, but concordance was consistently poor when ICD-10 harmful use diagnoses were compared with DSM-IV and DSM-III-R abuse diagnoses, Implications of these results are discussed in terms of the degree to which future research findings could be integrated with one another and the results from earlier studies using older versions of the DSM, to advance scientific knowledge in the drug and alcohol fields. RP Grant, BF (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,SUITE 514,6000 EXECUT BLVD,MSC 7003,BETHESDA,MD 20892, USA. NR 14 TC 87 Z9 87 U1 2 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 1996 VL 20 IS 8 BP 1481 EP 1488 DI 10.1111/j.1530-0277.1996.tb01152.x PG 8 WC Substance Abuse SC Substance Abuse GA VU644 UT WOS:A1996VU64400024 PM 8947328 ER PT J AU Gordis, E AF Gordis, E TI NIAAA 25th Anniversary: Advances in the neuroscience of alcohol SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article ID ETHANOL; EXPOSURE; LINKAGE; RISK; MECHANISMS; FEATURES; BRAIN; NERVE; BOYS; P300 RP Gordis, E (reprint author), NIAAA,BETHESDA,MD, USA. NR 38 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 1996 VL 20 IS 8 SU S BP A38 EP A44 DI 10.1111/j.1530-0277.1996.tb01742.x PG 7 WC Substance Abuse SC Substance Abuse GA VU966 UT WOS:A1996VU96600003 PM 8947231 ER PT J AU Gordis, E AF Gordis, E TI Alcohol research: Celebrating the past, building the future SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Editorial Material RP Gordis, E (reprint author), NIAAA,NIH,BETHESDA,MD, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 1996 VL 20 IS 8 SU S BP A32 EP A37 DI 10.1111/j.1530-0277.1996.tb01741.x PG 6 WC Substance Abuse SC Substance Abuse GA VU966 UT WOS:A1996VU96600002 PM 8947230 ER PT J AU Howard, J Boyd, GM AF Howard, J Boyd, GM TI Community organizing, public policy and the prevention of alcohol problems SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article ID TRIALS RP Howard, J (reprint author), NIAAA,PREVENT RES BRANCH,ROCKVILLE,MD 20852, USA. NR 44 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 1996 VL 20 IS 8 SU S BP A265 EP A269 DI 10.1111/j.1530-0277.1996.tb01789.x PG 5 WC Substance Abuse SC Substance Abuse GA VU966 UT WOS:A1996VU96600050 PM 8947278 ER PT J AU Litten, RZ Fertig, J AF Litten, RZ Fertig, J TI International update: New findings on promising medications SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article ID ALCOHOL DEPENDENCE; NALTREXONE RP Litten, RZ (reprint author), NIAAA,BETHESDA,MD, USA. NR 4 TC 11 Z9 11 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 1996 VL 20 IS 8 SU S BP A216 EP A218 DI 10.1111/j.1530-0277.1996.tb01779.x PG 3 WC Substance Abuse SC Substance Abuse GA VU966 UT WOS:A1996VU96600040 PM 8947268 ER PT J AU Martin, S Andreasson, S AF Martin, S Andreasson, S TI Zero tolerance laws: Effective public policy? SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article C1 ST GORANS UNIV HOSP,PSYCHIAT CLIN ADDICT,STOCKHOLM,SWEDEN. RP Martin, S (reprint author), NIAAA,ROCKVILLE,MD 20852, USA. NR 10 TC 4 Z9 4 U1 1 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 1996 VL 20 IS 8 SU S BP A147 EP A150 DI 10.1111/j.1530-0277.1996.tb01765.x PG 4 WC Substance Abuse SC Substance Abuse GA VU966 UT WOS:A1996VU96600026 PM 8947254 ER PT J AU Newlin, DB AF Newlin, DB TI Craving for alcohol and cocaine: From inside the brain to the clinic SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article RP Newlin, DB (reprint author), NATL INST DRUG ABUSE,INTRAMURAL RES PROGRAM,BALTIMORE,MD 21224, USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 1996 VL 20 IS 8 SU S BP A45 EP A47 DI 10.1111/j.1530-0277.1996.tb01743.x PG 3 WC Substance Abuse SC Substance Abuse GA VU966 UT WOS:A1996VU96600004 PM 8947232 ER PT J AU Song, BJ Cederbaum, AI AF Song, BJ Cederbaum, AI TI Ethanol-inducible cytochrome P450 (CYP2E1): Biochemistry, molecular biology and clinical relevance: 1996 update SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Review ID ALCOHOLIC LIVER-DISEASE; ACETALDEHYDE-PROTEIN ADDUCTS; HEPATOMA-CELL LINE; HIGH-FAT DIET; RAT-LIVER; LIPID-PEROXIDATION; 2E1 INDUCTION; TRANSCRIPTIONAL REGULATION; COMPLEMENTARY-DNA; RADICAL FORMATION C1 MT SINAI HOSP,SCH MED,DEPT BIOCHEM,NEW YORK,NY. RP Song, BJ (reprint author), NIAAA,NEUROGENET LAB,ROCKVILLE,MD 20852, USA. NR 120 TC 94 Z9 96 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 1996 VL 20 IS 8 SU S BP A138 EP A146 DI 10.1111/j.1530-0277.1996.tb01764.x PG 9 WC Substance Abuse SC Substance Abuse GA VU966 UT WOS:A1996VU96600025 PM 8947253 ER PT J AU Zakhari, S Szabo, G AF Zakhari, S Szabo, G TI NF-kappa B, a prototypical cytokine-regulated transcription factor: Implications for alcohol-mediated responses SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article ID TUMOR-NECROSIS-FACTOR; CELL-ADHESION MOLECULE-1; VASCULAR ENDOTHELIAL-CELLS; LOW-DENSITY-LIPOPROTEIN; DNA-BINDING ACTIVITY; FACTOR-ALPHA; C-JUN; INTERLEUKIN-6 GENE; HUMAN-FIBROBLASTS; VIRUS INDUCTION C1 UNIV MASSACHUSETTS,MED CTR,DEPT MED,WORCESTER,MA. RP Zakhari, S (reprint author), NIAAA,NIH,DIV BASIC RES,BETHESDA,MD, USA. NR 60 TC 13 Z9 13 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 1996 VL 20 IS 8 SU S BP A236 EP A242 DI 10.1111/j.1530-0277.1996.tb01783.x PG 7 WC Substance Abuse SC Substance Abuse GA VU966 UT WOS:A1996VU96600044 PM 8947272 ER PT J AU Cohen, SG AF Cohen, SG TI Asthma among the famous - A continuing series - Lemuel Shaw (1781-1860) - American jurist SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Item About an Individual RP Cohen, SG (reprint author), NIAID,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD NOV-DEC PY 1996 VL 17 IS 6 BP 365 EP 369 DI 10.2500/108854196778606338 PG 5 WC Allergy SC Allergy GA WC827 UT WOS:A1996WC82700011 PM 8993732 ER PT J AU Cohen, SG AF Cohen, SG TI Asthma among the famous - A continuing series - Martin Van Buren (1782-1862) - Eighth president of the United States SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Item About an Individual RP Cohen, SG (reprint author), NIAID,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD NOV-DEC PY 1996 VL 17 IS 6 BP 370 EP 372 PG 3 WC Allergy SC Allergy GA WC827 UT WOS:A1996WC82700012 PM 9091244 ER PT J AU Cohen, SG AF Cohen, SG TI Asthma among the famous - A continuing series - Daniel Webster (1782-1852) American lawyer, US senator, and statesman SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Item About an Individual RP Cohen, SG (reprint author), NIAID,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD NOV-DEC PY 1996 VL 17 IS 6 BP 373 EP 376 PG 4 WC Allergy SC Allergy GA WC827 UT WOS:A1996WC82700013 PM 9091245 ER PT J AU Cohen, SG AF Cohen, SG TI Asthma among the famous - A continuing series - Giacomo Leopardi (1798-1837) - Italian poet and author SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Item About an Individual RP Cohen, SG (reprint author), NIAID,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD NOV-DEC PY 1996 VL 17 IS 6 BP 377 EP 379 PG 3 WC Allergy SC Allergy GA WC827 UT WOS:A1996WC82700014 PM 9091246 ER PT J AU Dwyer, JH Li, L Dwyer, KM Curtin, LR Feinleib, M AF Dwyer, JH Li, L Dwyer, KM Curtin, LR Feinleib, M TI Dietary calcium, alcohol, and incidence of treated hypertension in the NHANES I epidemiologic follow-up study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE alcohol drinking; blood pressure; calcium, dietary; diet; hypertension ID BLOOD-PRESSURE; UNITED-STATES; NUTRITIONAL FACTORS; MILD HYPERTENSION; NATIONAL-HEALTH; ORAL CALCIUM; DOUBLE-BLIND; SUPPLEMENTATION; TRIAL AB Evidence concerning the relation between dietary calcium intake and development of hypertension is inconsistent. Some of this inconsistency may be due to interaction of this relation with other factors, The current study was designed to test for an interaction between alcohol consumption and the relation of dietary calcium intake to 10-year incidence of hypertension in a sample of the US adult population. the Epidemiologic Follow-up Study (1982-1984) of the First National Health and Nutrition Examination Survey (NHANES I) (1971-1975). Interactive logistic regression models were estimated with incident hypertension defined as self-reported treatment with antihypertensive medication, After exclusion of participants with evidence of hypertension at baseline (resulting n = 6,634), odds ratios for hypertension were estimated for each 1-g/day increase in calcium intake. The relation between dietary calcium and incident hypertension showed significant interactions with frequency of alcohol use (odds ratio (OR) = 1,33 for daily drinkers, OR = 0.84 for others; p = 0,005 for difference), age (OR = 0.75 for less than or equal to 40 years at baseline, OR = 1.00 for >40 years; p = 0.004), and body mass index, defined as weight (kg) divided by height (m) squared (OR = 0.82 for less than or equal to 26, OR = 1.01 for >26; p = 0.018). interactions with sex and race (black vs. white) were not significant (p greater than or equal to 0.4). These findings suggest that a protective effect of foods containing calcium on the risk of developing hypertension may vary across levels of alcohol consumption and other risk factors for hypertension. C1 UNIV SO CALIF,SCH MED,INST PREVENT RES,LOS ANGELES,CA 90033. NCI,BETHESDA,MD 20892. NATL CTR HLTH STAT,HYATTSVILLE,MD 20782. GEORGETOWN UNIV,MED CTR,DEPT MED,WASHINGTON,DC 20007. RP Dwyer, JH (reprint author), UNIV SO CALIF,SCH MED,DEPT PREVENT MED,LOS ANGELES,CA 90033, USA. NR 41 TC 21 Z9 23 U1 0 U2 1 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 1 PY 1996 VL 144 IS 9 BP 828 EP 838 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VQ234 UT WOS:A1996VQ23400003 PM 8890661 ER PT J AU Chambless, LE Shahar, E Sharrett, AR Heiss, G Wijnberg, L Paton, CC Sorlie, P Toole, JF AF Chambless, LE Shahar, E Sharrett, AR Heiss, G Wijnberg, L Paton, CC Sorlie, P Toole, JF TI Association of transient ischemic attack stroke symptoms assessed by standardized questionnaire and algorithm with cerebrovascular risk factors and carotid artery wall thickness - The ARIC study, 1987-1989 SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE atherosclerosis; cerebral ischemia, transient; cerebrovascular disorders; coronary disease; ethnic groups; risk factors; ultrasonography ID CORONARY HEART-DISEASE; LIFE-STYLE FACTORS; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; SERUM-CHOLESTEROL; FAMILY HISTORY; FIBRINOGEN; COPENHAGEN; COHORT; HYPERTENSION AB The baseline examination (1987-1989) for the Atherosclerosis Risk in Communities (ARIC) Study was conducted in 15,792 free-living residents aged 45-64 years in four geographically dispersed US communities. A questionnaire on symptoms of transient ischemic attack (TIA) and stroke was evaluated by computer algorithm for 12,205 of these participants. Data were also collected on lipoprotein levels, hemostasis, hematology, anthropometry, blood pressure, medical history, lifestyle, socioeconomic status, and medication use. Noninvasive high resolution B-mode ultrasonographic imaging was used to determine carotid arterial intimal-medial wall thickness (IMT). The cross-sectional relation between the prevalence of TIA/stroke symptoms and putative risk factors was assessed by logistic regression, controlling for age and community. Odds ratios for TIA/stroke symptoms were significantly elevated (p less than or equal to 0.01) for diabetes mellitus, current smoking, hypertension, lower levels of education, income, and work activity, and higher levels of lipoprotein(a), IMT, hemostasis factor VIII, and von Willebrand factor. However, the relations with education and carotid IMT were not present for black Americans. In whites, the relations of TIA/stroke symptoms to IMT were nonlinear. Only at extreme levels of IMT were symptoms substantially more frequent: For example, men with an IMT greater than 1.17 mm or women with an IMT greater than 0.85 mm had approximately twice the odds of having positive TIA/stroke symptoms as those with lower IMTs. The authors plan in future analyses to address the issue prospectively, as well as to examine the relation with magnetic resonance imaging-defined outcomes and clinically defined incident stroke. C1 UNIV N CAROLINA,SCH PUBL HLTH,DEPT BIOSTAT,CHAPEL HILL,NC. UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455. NHLBI,BETHESDA,MD 20892. UNIV N CAROLINA,SCH PUBL HLTH,DEPT EPIDEMIOL,CHAPEL HILL,NC. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT NEUROL,WINSTON SALEM,NC 27103. RP Chambless, LE (reprint author), UNIV N CAROLINA,COLLABORAT STUDIES COORDINATING CTR,137 E FRANKLIN ST,SUITE 203,CHAPEL HILL,NC 27514, USA. FU NHLBI NIH HHS [N01-HC-55015] NR 37 TC 43 Z9 45 U1 0 U2 1 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 1 PY 1996 VL 144 IS 9 BP 857 EP 866 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VQ234 UT WOS:A1996VQ23400006 PM 8890664 ER PT J AU Hayashi, PH Beames, MP Kuhns, MC Hoofnagle, JH DiBisceglie, AM AF Hayashi, PH Beames, MP Kuhns, MC Hoofnagle, JH DiBisceglie, AM TI Use of quantitative assays for hepatitis B e antigen and IgM antibody to hepatitis B core antigen to monitor therapy in chronic hepatitis B SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID IMMUNOGLOBULIN-M ANTIBODY; VIRUS-INFECTION; NATURAL COURSE; HBC AB Objectives: We evaluated the clinical utility of IgM antibody to the hepatitis B (HB) core antigen (anti-HBc) and HB e antigen (HBeAg) serum levels in patients with chronic HB receiving interferon alfa. Methods: Stored serum from 47 patients with chronic HB participating in a controlled trial of interferon alfa therapy (10 million U three times a week for 16 wk) were analyzed. All were seropositive for HB surface Ag, HBeAg, and HB virus (HBV) DNA before entry. IgM anti-HBc index values and HBeAg standard values were determined by automated microparticle enzyme immunoassay on samples drawn just before therapy and 6 months later. Ten normal subjects were tested as controls. IgM anti-HBc and HBeAg levels were compared to initial serum HBV DNA, DNA polymerase, serum aminotransferase levels, and demographic features. Serial IgM anti-HBc levels were also obtained during and after therapy in 10 responders and five nonresponders, and serial HBeAg levels were also obtained during and after therapy in four responders and four nonresponders. Results: Neither IgM anti-HBc nor HBeAg levels correlated significantly with values for serum HBV DNA, DNA polymerase, aminotransferases, or demographic features. The initial mean IgM anti-HBc level among the 15 responders to therapy (loss of HBeAg and HBV DNA from serum) was no different from that in nonresponders (mean 1.15 vs 1.27, p = not significant). However, the initial mean HBeAg level was significantly lower in responders than in nonresponders (749.4 vs 1356.4,p = 0.019). Among 10 responders, IgM anti-HBc levels decreased progressively over time, so that at latest follow-up (1.5-4 yr later, mean 2.6 yr), the mean had decreased from 1.325 to 0.312 (p = < 0.001). Among five nonresponders, the mean did not change significantly over 1.5-3 yr (mean 2.2 yr) (1.26 vs 1.08, p = not significant). HBeAg values fell in parallel with HBV DNA and DNA polymerase values in four responders tested but remained elevated in four nonresponders. Conclusions: HBeAg levels, but not IgM anti-HBc levels, are useful in predicting response to interferon alfa, with responders tending to have lower pretreatment HBeAg levels than nonresponders. HBeAg levels may be used to monitor response to interferon alfa in patients with chronic HB. C1 NIDDK,LIVER DIS SECT,NIH,BETHESDA,MD 20892. ABBOTT LABS,INFECT DIS MED AFFAIRS,ABBOTT PK,IL 60064. NR 15 TC 11 Z9 12 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD NOV PY 1996 VL 91 IS 11 BP 2323 EP 2328 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VT370 UT WOS:A1996VT37000013 PM 8931411 ER PT J AU Fedorova, OV French, AW Anderson, DE AF Fedorova, OV French, AW Anderson, DE TI Inhibition of erythrocyte Na,K-ATPase activity during anticipatory hypoventilation in micropigs SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE blood pressure; endogenous digitalis-like factors; hematocrit; hypoventilation; micropigs; Na,K-ATPase activity ID OUABAIN-LIKE COMPOUND; HYPERTENSION; PLASMA; RAT; SODIUM; MARINOBUFAGENIN; ATPASE; AORTA; DOGS AB Previous studies with micropigs showed that conditioned suppression of respiration preceding the onset of an avoidance task was associated with increased pCO(2), decreased plasma pH, decreased hematocrit, and increased blood pressure with no change in heart rate. Voluntary hypoventilation by humans, which evoked similar effects, was found to elicit increases in plasma endogenous digitalis-like factors (EDLF) and decreases in erythrocyte Na,K-ATPase. The present study investigated plasma EDLF and Na,K-ATPase activity in micropigs preceding and during avoidance sessions. Compared with levels in a controlled environment, Ih of quiet waiting for the onset of a 30-min avoidance task was associated with hypoventilation, acidification of the plasma, and a decrease in hematocrit with progressive increases in plasma EDLF, and decreases in erythrocyte Na,K-ATPase activity (1.67 +/- 0.35 v 2.73 +/- 0.24 mu mol P-i/mL er/h). Systolic blood pressure increased (126.5 +/- 5.7 v 121.7 +/- 4.2 mm Hg) during preavoidance periods, with no changes in heart rate (89.5 +/- 3.9 v 89.4 +/- 4.0 beats/min). During the avoidance sessions, plasma EDLF, systolic blood pressure (126.7 +/- 4.5 mm Hg), and heart rate (107.3 +/- 4.8 beats/min) were elevated above the first 10 min of preavoidance, whereas Na,K-ATPase activity returned toward control values (2.46 +/- 0.83 mu mol P-i/mL er/h). These Endings are consistent with the view that elevation of blood pressure during behaviorally induced hypoventilation in micropigs is mediated in part by inhibition of Na,K-ATPase by increases in plasma EDLF due to expanded plasma volume. C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 25 TC 23 Z9 23 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD NOV PY 1996 VL 9 IS 11 BP 1126 EP 1131 DI 10.1016/0895-7061(96)00194-X PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VT085 UT WOS:A1996VT08500011 PM 8931839 ER PT J AU Min, YI CorreaVillasenor, A Stewart, PA AF Min, YI CorreaVillasenor, A Stewart, PA TI Parental occupational lead exposure and low birth weight SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE occupation; lead exposure; low birth weight; preterm birth; small for gestational age ID CONGENITAL-MALFORMATIONS; ORGANIC-SOLVENTS; REPRODUCTION; POPULATION; CHILDREN; WORKERS; GROWTH; BLOOD AB This study suggests that paternal occupational lead exposure may be associated with low birth weight in the offspring. The odds of low birth weight rose fivefold among infants of fathers who were potentially exposed to high levels of lead during the period 6 months before pregnancy to the end of pregnancy (adjusted odds ratio (aOR) = 4.7, 95% confidence interval (CI) = 1.1-20). This effect was most prominent for low-birth-weight infants who were both preterm and small for gestational age. There was a suggestion of a gradual increase of the odds of low birth weight at medium levels of exposure, but this increase was not statistically significant. No increased odds was observed at low levels of exposure. Low birth weight was not associated with paternal ever ver,rus never exposure, indirect exposure, or exposure frequency. Art independent effect of exposure duration could not be evaluated as it was highly correlated with exposure level. (C) 1996 Wiley-Liss, Inc. C1 NCI,ENVIRONM EPIDEMIOL BRANCH,OCCUPAT STUDIES SECT,BETHESDA,MD 20892. RP Min, YI (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,615 N WOLFE ST,ROOM 6019,BALTIMORE,MD 21205, USA. FU NHLBI NIH HHS [R37-HL25629]; NIEHS NIH HHS [R29 ES062] NR 32 TC 28 Z9 28 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 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD NOV PY 1996 VL 30 IS 5 BP 569 EP 578 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VP546 UT WOS:A1996VP54600005 PM 8909605 ER PT J AU Tedeschi, G Bertolino, A Campbell, G Barnett, AS Duyn, JH Jacob, PK Moonen, CTW Alger, JR DiChiro, G AF Tedeschi, G Bertolino, A Campbell, G Barnett, AS Duyn, JH Jacob, PK Moonen, CTW Alger, JR DiChiro, G TI Reproducibility of proton MR spectroscopic imaging findings SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article DE brain, magnetic resonance; efficacy studies; magnetic resonance spectroscopy ID MAGNETIC-RESONANCE SPECTROSCOPY; HUMAN BRAIN AB PURPOSE: To study the intraindividual, interindividual, and intraregional reproducibility of multisection proton MR spectroscopic imaging in healthy adults. METHODS: six subjects were studied three times with proton MR spectroscopic imaging. Multisection long-echo-time proton MR spectroscopic imaging permits simultaneous acquisition of N-acetylaspartate (NAA), choline-containing compounds (Cho), and creatine plus phosphocreatine (Cr) signal intensities from four 15-mm-thick sections divided into 0.84-mL single-volume elements. Regions of interest were the frontal cortex, the occipital cortex, the parietal cortex, the insular cortex, the cingulate gyrus, the centrum semiovale, the thalamus, and the caudate. Statistical evaluation was performed by analyses of variance and components of variance method. RESULTS: The ratio NAA/Cr showed the lowest overall coefficient of variation (CV, %) in most of the regions of interest (range, 8.9 to 26.1). Interregional differences in the overall CV were present. Interindividual CVs ranged from 4.2 to 8.7 for NAA/Cr, from 6.8 to 17.4 for NAA/Cho, and from 5.0 to 13.6 for Cho/Cr, Intraindividual CVs ranged from 8.2 to 22.2 For NAA/Cr, from 12.8 to 25.8 for NAA/Cho, and from 4.5 to 21.0 for Cho/Cr. Intraregional CVs ranged from 12.3 to 21.2 for NAA/Cr, from 13.0 to 20.4 For NAA/Cho, and from 12.2 to 18.9 for Cho/Cr. CONCLUSIONS: Proton MR spectroscopic imaging showed good overall reproducibility, The finding of interregional variations of CV indicates that care is needed when using this imaging technique for follow-up studies. C1 NINCDS,NEUROIMAGING BRANCH,BETHESDA,MD 20892. NINCDS,BIOMETRY & FIELD STUDIES BRANCH,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,DEPT RADIOL SCI,LOS ANGELES,CA 90024. NIH,VIVO NMR RES CTR,NATL CTR RES RESOURCES,BETHESDA,MD 20892. NIH,LAB DIAGNOST RADIOL RES,OFF DIRECTOR,BETHESDA,MD 20892. RI Duyn, Jozef/F-2483-2010; Moonen, Chrit/K-4434-2016; Bertolino, Alessandro/O-6352-2016 OI Moonen, Chrit/0000-0001-5593-3121; Bertolino, Alessandro/0000-0002-1251-1380 NR 19 TC 44 Z9 45 U1 0 U2 2 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD NOV-DEC PY 1996 VL 17 IS 10 BP 1871 EP 1879 PG 9 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA VU080 UT WOS:A1996VU08000011 PM 8933871 ER PT J AU Drass, JA Peterson, A AF Drass, JA Peterson, A TI Type II diabetes - Exploring treatment options SO AMERICAN JOURNAL OF NURSING LA English DT Article C1 US HLTH CARE FINANCING ADM,BALTIMORE,MD 21207. RP Drass, JA (reprint author), NIH,CTR CLIN,DEPT NURSING,BETHESDA,MD 20892, USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD NOV PY 1996 VL 96 IS 11 BP 45 EP 49 DI 10.2307/3464983 PG 5 WC Nursing SC Nursing GA VQ847 UT WOS:A1996VQ84700032 PM 8918355 ER PT J AU Copper, RL Goldenberg, RL Das, A Elder, N Swain, M Norman, G Ramsey, R Cotroneo, P Collins, BA Johnson, F Jones, P Meier, A Northern, A Meis, PJ MuellerHeubach, E Frye, A Mowad, AH Miodovnik, M Siddiqi, TA Bain, R Thom, E Leuchtenburg, L Fischer, M Paul, RH Kovacs, B Rabello, Y Caritis, S Harger, JH Cotroneo, M Stallings, C McNellis, D Yaffee, S Catz, C Klebanoff, M Iams, JD Landon, MB Thurnau, GR Carey, JC VanDorsten, JP Neuman, RB LeBoeuf, F Sibai, B Mercer, B Fricke, J Bottoms, SF Dombrowski, MP AF Copper, RL Goldenberg, RL Das, A Elder, N Swain, M Norman, G Ramsey, R Cotroneo, P Collins, BA Johnson, F Jones, P Meier, A Northern, A Meis, PJ MuellerHeubach, E Frye, A Mowad, AH Miodovnik, M Siddiqi, TA Bain, R Thom, E Leuchtenburg, L Fischer, M Paul, RH Kovacs, B Rabello, Y Caritis, S Harger, JH Cotroneo, M Stallings, C McNellis, D Yaffee, S Catz, C Klebanoff, M Iams, JD Landon, MB Thurnau, GR Carey, JC VanDorsten, JP Neuman, RB LeBoeuf, F Sibai, B Mercer, B Fricke, J Bottoms, SF Dombrowski, MP TI The preterm prediction study: Maternal stress is associated with spontaneous preterm birth at less than thirty-five weeks' gestation SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE psychosocial characteristics; stress; preterm birth; fetal growth restriction; low birth weight ID PSYCHOSOCIAL STRESS; GROWTH-RETARDATION; SOCIAL SUPPORT; FETAL GROWTH; LIFE STRESS; PREGNANCY; WEIGHT; DELIVERY; SMOKING; INFANT AB OBJECTIVE: Our purpose was to determine whether various measures of poor psychosocial status in pregnancy are associated with spontaneous preterm birth, fetal growth restriction, or low birth weight. STUDY DESIGN: Anxiety, stress, self-esteem, mastery, and depression were assessed at 25 to 29 weeks in 2593 gravid women by use of a 28-item Likert scale. Scores for each psychosocial subscale were determined, and an overall psychosocial score was calculated. Scores were divided into quartiles, and the lowest quartile scores were used to define poor psychosocial status. The percent spontaneous preterm birth, low birth weight, and fetal growth restriction in women with low and high psychosocial scores were compared. Logistic regression analyses provided the odds ratios and 95% confidence intervals. RESULTS: Analyses revealed that stress was significantly associated with spontaneous preterm birth and with low birth weight with odds ratios of 1.16, p = 0.003, and 1.08, p = 0.02, respectively, for each point on the scale. A low score on the combined scale or on any subscale other than stress did not predict spontaneous preterm birth, fetal growth restriction, or low birth weight. After multivariate adjustment was performed for psychosocial status, substance use, and demographic traits, black race was the only variable significantly associated with spontaneous preterm birth, fetal growth restriction, and low birth weight; stress and low education were associated with spontaneous preterm birth and low birth weight. CONCLUSION: Stress was associated with spontaneous preterm birth and low birth weight even after adjustment for maternal demographic and behavioral characteristics. Black race continues to be a significant predictor of spontaneous preterm birth, fetal growth restriction, and low birth weight even after adjustment for stress, substance use, and other demographic factors. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. UNIV CHICAGO,CHICAGO,IL 60637. UNIV CINCINNATI,CINCINNATI,OH 45221. GEORGE WASHINGTON UNIV,CTR BIOSTAT,WASHINGTON,DC 20052. UNIV SO CALIF,LOS ANGELES CTY MED CTR,LOS ANGELES,CA 90089. UNIV PITTSBURGH,PITTSBURGH,PA 15260. NICHHD,BETHESDA,MD 20892. OHIO STATE UNIV,COLUMBUS,OH 43210. UNIV OKLAHOMA,NORMAN,OK 73019. MED UNIV S CAROLINA,CHARLESTON,SC 29425. UNIV TENNESSEE,KNOXVILLE,TN 37996. WAYNE STATE UNIV,DETROIT,MI 48202. RP Copper, RL (reprint author), UNIV ALABAMA,BIRMINGHAM,AL, USA. FU NICHD NIH HHS [HD21410, HD21414, HD21434] NR 24 TC 342 Z9 350 U1 2 U2 24 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 NOV PY 1996 VL 175 IS 5 BP 1286 EP 1292 DI 10.1016/S0002-9378(96)70042-X PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA VU514 UT WOS:A1996VU51400026 PM 8942502 ER PT J AU Goldenberg, RL Cliver, SP Mulvihill, FX Hickey, CA Hoffman, HJ Klerman, LV Johnson, MJ AF Goldenberg, RL Cliver, SP Mulvihill, FX Hickey, CA Hoffman, HJ Klerman, LV Johnson, MJ TI Medical, psychosocial, and behavioral risk factors do not explain the increased risk for low birth weight among black women SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE preterm birth; growth restriction; birth weight; risk factors ID NORTH-AMERICAN WOMEN; CIGARETTE-SMOKING; PRETERM DELIVERY; GESTATIONAL-AGE; STRESS; INFECTION; GROWTH; DIET; GAIN AB OBJECTIVE: Our purpose was to determine whether various demographic, behavioral, housing, psychosocial, or medical characteristics explain the difference in pregnancy outcome between black and white women. STUDY DESIGN: A sample of 1491 multiparous women with singleton pregnancies, 69% of whom were black and 31% of whom were white and who enrolled for care between Oct. 1, 1985, and March 30, 1988, participated in the study. The frequencies of various demographic, medical environmental, and psychosocial risk factors among black and white women were determined. The outcome measures were birth weight, gestational age, fetal growth restriction, preterm delivery and low birth weight. RESULTS: White infants were heavier and born later than black infants. The white women in this sample smoked more cigarettes, moved more frequently, and had worse psychosocial scores. The black women had lower incomes, were less likely to be married, and had more hypertension, anemia, and diabetes. Besides race, only maternal height, weight, blood pressure, diabetes, and smoking had a consistent impact on outcome and did not explain the difference in outcome between the two groups. CONCLUSION: In this low-income population, many of the risk factors for low birth weight were more common among white women than black women. Nevertheless, black women had more infants born preterm, with growth restriction, and with low birth weight than did white women. The various maternal characteristics studied did not explain these differences. C1 UNIV ALABAMA,SCH PUBL HLTH,DEPT MATERNAL & CHILD HLTH,BIRMINGHAM,AL 35294. NATL INST DEAFNESS & OTHER COMMUN DISORDERS,BETHESDA,MD. RP Goldenberg, RL (reprint author), UNIV ALABAMA,DEPT OBSTET & GYNECOL,DIV MATERNAL FETAL MED,CTR OBSTET RES,BIRMINGHAM,AL 35294, USA. FU NICHD NIH HHS [N01-HD-4-2811]; PHS HHS [ASPH12B052] NR 25 TC 158 Z9 159 U1 0 U2 2 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 NOV PY 1996 VL 175 IS 5 BP 1317 EP 1324 DI 10.1016/S0002-9378(96)70048-0 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA VU514 UT WOS:A1996VU51400032 PM 8942508 ER PT J AU Irak, I Zangwill, L Garden, V Shakiba, S Weinreb, RN AF Irak, I Zangwill, L Garden, V Shakiba, S Weinreb, RN TI Change in optic disk topography after trabeculectomy SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID INTRAOCULAR-PRESSURE REDUCTION; NERVE HEAD; GLAUCOMA; ADULTS AB PURPOSE: To investigate the relationship between optic disk topography and intraocular pressure before and after trabeculectomy with confocal scanning laser ophthalmoscopy. METHODS: The eyes of 49 consecutive patients undergoing trabeculectomy at a university based glaucoma practice underwent preoperative and postoperative imaging using a confocal scanning laser ophthalmoscope (Heidelberg Retina Tomograph). Three images of one eye of each patient were obtained with a 15-degree field of view, Preoperative images were obtained approximately 2 months before surgery (mean +/- SD, 2.4 +/- 1.6 months). Postoperative images were obtained at least 3 months after surgery (mean, 4.5 +/- 2.6 months). RESULTS: Mean preoperative intraocular pressure, postoperative intraocular pressure, and percent change in intraocular pressure respectively were 23.1 +/- 6.8 mm Hg, 12.7 +/- 7.1 mm Hg, and 43.8% +/- 29.9%, A significant association (P < .01) was found between percent decrease in intra ocular pressure and decreases in cup area, cup volume, and cup/disk area ratio as well as between percent decrease in intraocular pressure and increases in rim area, rim volume, mean height contour, retinal cross-section area, and height in contour. Between 11.7% and 31.2% of the variability (R(2)) in these parameters was explained by the percent change in intraocular pressure, Topography changes were more strongly associated with percent change than with mean change in intraocular pressure, We found no association between percent decrease in intraocular pressure and reference plane height or maximum cup depth. CONCLUSIONS: Changes in optic nerve topography were associated with reduction in intraocular pressure after trabeculectomy. C1 UNIV CALIF SAN DIEGO,GLAUCOMA CTR,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,RES LABS,LA JOLLA,CA 92093. NEI,BETHESDA,MD 20892. FU NEI NIH HHS [EY11008, R01 EY011008, EY11158, R01 EY011008-05] NR 15 TC 65 Z9 68 U1 0 U2 1 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD NOV PY 1996 VL 122 IS 5 BP 690 EP 695 PG 6 WC Ophthalmology SC Ophthalmology GA VQ701 UT WOS:A1996VQ70100010 PM 8909209 ER PT J AU Saffiotti, U AF Saffiotti, U TI Alveolar type II cells at the crossroad of inflammation, fibrogenesis, and neoplasia SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Editorial Material ID LUNG EPITHELIAL-CELLS; EXTRACELLULAR-MATRIX BIOSYNTHESIS; GROWTH-FACTOR; FIBROBLAST INTERACTIONS; FETAL; CULTURE; BETA RP Saffiotti, U (reprint author), NCI,LAB EXPT PATHOL,BLDG 41,ROOM C-105,BETHESDA,MD 20892, USA. NR 29 TC 10 Z9 10 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 1996 VL 149 IS 5 BP 1423 EP 1426 PG 4 WC Pathology SC Pathology GA VQ237 UT WOS:A1996VQ23700001 PM 8909230 ER PT J AU Valente, G Secchiero, P Lusso, P Abele, MC Jemma, C Reato, G Kerim, S Gallo, RC Palestro, G AF Valente, G Secchiero, P Lusso, P Abele, MC Jemma, C Reato, G Kerim, S Gallo, RC Palestro, G TI Human herpesvirus 6 and Epstein-Barr virus in Hodgkin's disease - A controlled study by polymerase chain reaction and in situ hybridization SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID BLOOD MONONUCLEAR-CELLS; REED-STERNBERG CELLS; INSITU HYBRIDIZATION; LYMPHOPROLIFERATIVE DISORDERS; LYMPHOID MALIGNANCY; FREQUENT DETECTION; HIGH PREVALENCE; DNA; INFECTION; SEQUENCES AB Human herpesvirus-6 (HHV-6), a T-lymphotropic double-stranded DNA virus highly endemic in human populations, has been suggested to play a possible role in the development of lymphoid neoplasms, especially Hodgkin's disease, To investigate this point, we evaluated the presence and distribution of HHV-6 DNA by Southern blot, nested polymerase chain reaction, and in situ hybridization in a series of lymphoproliferative disorders including 73 Hodgkin's disease cases, 15 non-Hodgkin lymphomas, and 19 reactive lymph nodes, A high prevalence of HHV-6 infection was observed within the Hodgkin's disease category by polymerase chain reaction (38 of 52, 73%) and in situ hybridization (47 of 57, 82.4%); however, a similar prevalence was found in non-Hodgkin's lymphomas (10 of 15, 66.6%) and reactive lymph nodes (13 of 19, 68.4%), In no case did Southern blot detect viral DNA, suggesting that the neoplastic tissue contained a low number of HHV-6 copies, In situ hybridization showed that the HHV-6 positivity was restricted to lymphocytes, whereas Hodgkin and Reed-Sternberg cells were consistently negative. Immunohistochemical staining with specific monoclonal antibodies against viral structural proteins was also negative, indicating the absence of a productive infection, No relationship tons observed between HHV-6 positivity and histological type, clinical parameter, and outcome of the disease In the same series, a high proportion of cases (33 of 52, 75%) showed the presence of the Epstein-Barr virus (EBV) genome by polymerase chain reaction; in situ hybridization for Epstein-Barr-virus-encoded small RNA and immunohistochemical detection of latent membrane protein-1 gave similar results (73.6% of positive cases with both methods). In 54.9% of the cases, both sequences of HHV-6 and Epstein-Barr virus DNA were found, suggesting that a synergism of the two viruses may occur. However, the lack of detectable HHV-6 DNA in Reed-Sternberg and Hodgkin's cells seems to argue against such an interpretation. Based on these results, HHV-6 does not appear to play a specific role in the pathogenesis of Hodgkin's disease. C1 UNIV TURIN,SAN GIOVANNI HOSP,TURIN,ITALY. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. SAN RAFFAELE SCI INST,DEPT BIOL & TECHNOL RES,UNIT HUMAN VIROL,I-20132 MILAN,ITALY. RP Valente, G (reprint author), UNIV TURIN,SCH MED,DIPARTIMENTO SCI BIOMED & ONCOL UMANA,VIA SANTENA 7,I-10126 TURIN,ITALY. RI Valente, Guido/B-9714-2013; secchiero, paola/G-9689-2015 OI secchiero, paola/0000-0003-4101-7987 NR 55 TC 36 Z9 36 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 1996 VL 149 IS 5 BP 1501 EP 1510 PG 10 WC Pathology SC Pathology GA VQ237 UT WOS:A1996VQ23700011 PM 8909240 ER PT J AU Pottathil, M Nakatsuji, Y Alter, HJ Shih, JWK AF Pottathil, M Nakatsuji, Y Alter, HJ Shih, JWK TI Detection and quantitation of hepatitis G virus RNA RT/PCR product with digoxigenin chemiluminescence SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Meeting Abstract C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 1996 VL 149 IS 5 BP ID12 EP ID12 PG 1 WC Pathology SC Pathology GA VQ237 UT WOS:A1996VQ23700083 ER PT J AU Kirshman, P Meng, L Rago, Z Nadji, M Sobel, ME AF Kirshman, P Meng, L Rago, Z Nadji, M Sobel, ME TI Decreased levels of lactate dehydrogenase-B mRNA in progesterone receptor-positive human breast tumors. SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Meeting Abstract C1 NCI,MOL PATHOL SECT,BETHESDA,MD 20892. UNIV MIAMI,MIAMI,FL 33101. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 1996 VL 149 IS 5 BP ST3 EP ST3 PG 1 WC Pathology SC Pathology GA VQ237 UT WOS:A1996VQ23700089 ER PT J AU Sherer, DM Spong, CY Minior, VK Salafia, CM AF Sherer, DM Spong, CY Minior, VK Salafia, CM TI Decreased amniotic fluid volume at < 32 weeks of gestation is associated with decreased fetal movements SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE amniotic fluid volume; fetal movements; prematurity ID PREMATURE RUPTURE; BIOPHYSICAL PROFILE; MEMBRANES; PREGNANCY; INDEX AB The objective of this study was to assess the relationship between amniotic fluid volume (AFV) and fetal movements at < 32 weeks gestation as assessed by routine biophysical profile (BPP). From a database of 465 consecutive nonhypertensive, nondiabetic patients delivering at < 32 weeks gestation, patients with singleton, nonanomalous fetuses with AFV and fetal movements determined as part of a BPP assessment within 24 hours of delivery were studied. Amniotic fluid volume was scored 0 to 2, according to the following criteria:largest pocket in vertical diameter < 1 cm = 0; < 2 but > 1 cm = 1; greater than or equal to 2 cm = 2. Fetal movements (FM) were scored over 30 minutes: O if absent, 1 if 1 to 2 movements, 2 if greater than or equal to 3 gross (limb/trunk) movements. Variables assessed included fetal presentation, gestational age (GA), premature rupture of membranes (FROM) as a principal indication for delivery, clinical chorioamnionitis (diagnosed by previously published criteria), histologic parameters of infection (in amnion and umbilical cord assessed by a single pathologist blinded to clinical data), and neonatal outcome. Statistical analyses included contingency tables and analysis of variance with p < 0.05 considered significant. Three hundred and fifty-two patients met the inclusion criteria. One hundred and sixty-seven patients (47%) had FROM as a primary indication for delivery. Infrequently, decreased fetal well-being manifested by a BPP < 7 of 10 points was an indication for delivery despite prematurity (n = 7). Of the 352 patients, 80 (23%) had AFV = 0, 60 (17%) had AFV = 1, and 212 (60%) had AFV = 2; and 12 (3%) had FM = 0, 30 (9%) FM = 1, and 310 (88%) FM = 2. There was a significant correlation between decreased AFV and decreased fetal movements (p < 0.0001). Fetal presentation and GA were not significantly different between patients based on score of fetal movements. The incidence of clinical chorioamnionitis was significantly greater in patients with FM = 0 (p < 0.005). We conclude that decreased AFV is associated with decreased fetal movements irrespective of fetal presentation or gestational age. Neonatal outcome (umbilical vasculitis, sepsis, intraventricular hemorrhage) is affected only in unusual cases in which otherwise uncompromised (nonhypoxic, nonacidotic) fetuses have low scores on both these antepartum ultrasonographic parameters. C1 NICHHD,PERINATAL RES FACIL,INTRAMURAL DIV,NIH,BETHESDA,MD 20892. FU NICHD NIH HHS [N01-HD-3-3198] NR 11 TC 17 Z9 17 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 SN 0735-1631 J9 AM J PERINAT JI Am. J. Perinatol. PD NOV PY 1996 VL 13 IS 8 BP 479 EP 482 DI 10.1055/s-2007-994431 PG 4 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA WA768 UT WOS:A1996WA76800005 PM 8989478 ER PT J AU Chang, AS Dillingham, TR Yu, KF AF Chang, AS Dillingham, TR Yu, KF TI Statistical methods of computing reference values for side-to-side differences in nerve conduction studies SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE statistics; nerve conduction; reference values; side-to-side; normal values; electromyography; reference ranges ID REFLEX AB This study uses theoretic derivations, statistical simulations, and empirical estimations to compare two ways of deriving reference values for side-to-side differences in nerve conduction parameters of healthy subjects. The two methods involve using the side-to-side differences (STSD) and the absolute values of the STSD (AVSTSD). The theoretic derivations showed that the population reference value of the AVSTSD is greater than the STSD reference values by 0.18%. Simulation studies showed that the AVSTSD yields greater sampling errors than the STSD method when establishing the reference values for nerve conduction parameters. However, the sampling variability is substantially reduced by using study samples of greater than 50, and the differences between the two methods in sampling errors ave trivial as sample size approaches 100. Using H reflex (HR) and extensor digitorum brevis reflex (EDBR) clinical data, the two methods were compared. In contrast to the small theoretic differences in reference values, the AVSTSD method overestimated the reference value by 0.5 ms for the EDBR and 0.1 ms for the H reflex, when using data from a population sample, increasing the type II error (reducing sensitivity) far the EDBR. The STSD method is recommended for establishment of normal values and for clinical comparisons. C1 JOHNS HOPKINS UNIV,DEPT PHYS MED & REHABIL,BALTIMORE,MD. NICHHD,BIOMETRY & MATH STAT BRANCH,DIV EPIDEMIOL STAT & PREVENT RES,NIH,BETHESDA,MD 20892. RP Chang, AS (reprint author), WALTER REED ARMY MED CTR,DEPT CLIN INVEST,RES REVIEW SERV,BLDG 6,ROOM 4046,WASHINGTON,DC 20307, USA. NR 17 TC 12 Z9 13 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD NOV-DEC PY 1996 VL 75 IS 6 BP 437 EP 442 DI 10.1097/00002060-199611000-00007 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA WA783 UT WOS:A1996WA78300006 PM 8985107 ER PT J AU Shea, MT Leon, AC Mueller, TI Solomon, DA Warshaw, MG Keller, MB AF Shea, MT Leon, AC Mueller, TI Solomon, DA Warshaw, MG Keller, MB TI Does major depression result in lasting personality change? SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID AFFECTIVE-DISORDERS; FEATURES; STATE AB Objective: Individuals with a history of depression are characterized by high levels of certain personality traits, particularly neuroticism, introversion, and interpersonal dependency. The authors examined the ''scar hypothesis,'' i.e., the possibility that episodes of major depression result in lasting personality changes that persist beyond recovery from the depression. Method: A large sample of first-degree relatives, spouses, and comparison subjects ascertained in connection with the proband sample from the National Institute of Mental Health Collaborative Program on the Psychobiology of Depression were assessed at two points in time separated by an interval of 6 years. Subjects with a prospectively observed first episode of major depression during the interval were compared with subjects remaining well in terms of change from time 1 to time 2 in self-reported personality traits. All subjects studied were well (had no mental disorders) at the time of both assessments. Results: There was no evidence of negative change from premorbid to postmorbid assessment in any of the personality traits for subjects with a prospectively observed first episode of major depression during the interval. The results suggested a possible association of number and length of episodes with increased levels of emotional reliance and introversion, respectively. Conclusions: The findings suggest that self-reported personality traits do not change after a typical episode of major depression. Future studies are needed to determine whether such change occurs following more severe, chronic, or recurrent episodes of depression. C1 NIMH,COLLABORAT PROGRAM PSYCHOBIOL DEPRESS CLIN STUDIE,BETHESDA,MD. FU NIMH NIH HHS [R01 MH025478] NR 24 TC 99 Z9 100 U1 4 U2 6 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 1996 VL 153 IS 11 BP 1404 EP 1410 PG 7 WC Psychiatry SC Psychiatry GA VP754 UT WOS:A1996VP75400005 PM 8890672 ER PT J AU Fee, E AF Fee, E TI The pleasures and perils of prophetic advocacy: Henry E. Sigerist and the politics of medical reform SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Review ID HEALTH; PROGRAMS; DISEASE AB Henry E. Sigerist, an internationally renowned medical historian, played a surprisingly important and visible role in American medical politics in the 1930s and 1940s. Born in Paris of Swiss parents, he was professor in Leipzig, Germany, before coming to the United States in 1932 as professor of the history of medicine at Johns Hopkins University. Once in America, Sigerist became deeply involved in medical politics and the campaign for national health insurance. He argued that individualized medical practice was outdated and should gradually be superseded by state-run and state-financed health services. National health insurance was but one step in this historical progression. Sigerist thus lent the weight of history itself to the cause of medical care reform. The charming and erudite Sigerist was welcomed by the leaders of academic medicine in America. Soon, he emerged as a spokesman of the left wing of the medical profession, an effective and popular speaker, and an impassioned advocate of socialized medicine. This paper traces Sigerist's political ideas and activities, and his contributions toward medical care reform in the United States. RP Fee, E (reprint author), NATL LIB MED,HIST MED DIV,BLDG 38,ROOM 1E21,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 104 TC 2 Z9 2 U1 1 U2 1 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 1996 VL 86 IS 11 BP 1637 EP 1647 DI 10.2105/AJPH.86.11.1637 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VT363 UT WOS:A1996VT36300026 PM 8916536 ER PT J AU Svinarich, DM Bitonti, OM Araneda, H Romero, R Gonik, B AF Svinarich, DM Bitonti, OM Araneda, H Romero, R Gonik, B TI Induction and postranslational expression of G-CSF and RANTES in a first trimester trophoblast cell line by lipopolysaccharide SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 20-23, 1996 CL PHILADELPHIA, PA SP Soc Gynecol Investigat DE cytokines; infection; LPS; trophoblasts; immune signaling ID CYTOKINES; BIOLOGY; FAMILY AB PROBLEM: Comparatively little is known about the capacity of first trimester trophoblasts to respond to an infection and coordinate an immune response. This study characterizes the LPS induction of G-CSF and RANTES in a first trimester trophoblast cell line. METHODS: HTR-8/SV neo cells were exposed to LPS (1 mu g/ml) for 0, 2, 4, 6, 8, and 24 hours in DMEM-Ham's F-12 media supplemented with 10% fetal bovine serum. Cytokine levels in culture supernatants were measured by ELISA. Northern analysis of total RNA was conducted using antisense cytokine probes. RESULTS: Levels of immunoreactive G-CSF and RANTES from LPS induced cultures at 24 hours were 10-fold and 8.5-fold greater than cytokine levels from non-induced cells at 24 hours, respectively (P<0.01). Under LPS induction, maximal rates of G-CSF and RANTES transcription occurred at 24 hours and 8 hours, respectively. CONCLUSION: The LPS induction of proinflammatory cytokines in a first trimester trophoblast cell line supports the contention that first trimester trophoblasts participate in cytokine based immune signaling in response to infection. C1 NICHHD,PERINATOL RES BRANCH,BETHESDA,MD. RP Svinarich, DM (reprint author), WAYNE STATE UNIV,SCH MED,DEPT OBSTET & GYNECOL,CS MOTT CTR,275 E HANCOCK AVE,DETROIT,MI 48201, USA. NR 12 TC 10 Z9 10 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 8755-8920 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD NOV PY 1996 VL 36 IS 5 BP 256 EP 259 PG 4 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA VT373 UT WOS:A1996VT37300003 PM 8955501 ER PT J AU Coin, PG OsornioVargas, AR Roggli, VL Brody, AR AF Coin, PG OsornioVargas, AR Roggli, VL Brody, AR TI Pulmonary fibrogenesis after three consecutive inhalation exposures to chrysotile asbestos SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID RAT ALVEOLAR MACROPHAGES; DEPOSITION PATTERN; LUNG FIBROBLASTS; PROLIFERATION; FIBERS; CLEARANCE; FIBROSIS; ALPHA; MICE; AA AB Previously, this laboratory developed a model of asbestos-induced pulmonary fibrogenesis in rats and mice after a brief (1 to 3-h) inhalation exposure. However, typical human environmental exposures would be repeated, although at lower concentrations than those used in our animal model. Here we have extended this model to encompass repeated exposures and consequent long-term effects. Groups of rats were exposed to chrysotile aerosol (10 mg/m(3)) for 3- to 5-h periods over 3 consecutive days. Lung fiber burden and pathologic features were studied for as long as 6 mo after exposure. We found that many of the longest (greater than or equal to 8 mu m) fibers were retained in the lung for at least 6 mo, whereas shorter fibers were cleared more rapidly. The three exposures to chrysotile caused a large increase in DNA synthesis in the epithelium of terminal bronchioles and more proximal airways. When compared with a single exposure, the triple exposure caused an enhanced inflammatory response as well as a prolonged period of increased DNA synthesis in the proximal alveolar region. Hyperplastic, fibrotic lesions subsequently developed in the same region and persisted for at least 6 mo after exposure. These findings will be valuable in directing future studies of the mechanisms of pulmonary fibrosis in this model. C1 VET AFFAIRS MED CTR,DEPT PATHOL,DURHAM,NC 27705. RP Coin, PG (reprint author), NIEHS,PULM PATHOBIOL LAB,MAIL DROP D2-02,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Osornio Vargas, Alvaro/D-4012-2009; Osornio Vargas, Alvaro/B-4645-2010 OI Osornio Vargas, Alvaro/0000-0001-8287-7102 NR 27 TC 19 Z9 20 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV PY 1996 VL 154 IS 5 BP 1511 EP 1519 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA VT369 UT WOS:A1996VT36900045 PM 8912773 ER PT J AU Gupta, S Feng, LL Yoshimura, T Redick, J Fu, SM Rose, CE AF Gupta, S Feng, LL Yoshimura, T Redick, J Fu, SM Rose, CE TI Intra-alveolar macrophage-inflammatory peptide 2 induces rapid neutrophil localization in the lung SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID RESPIRATORY-DISTRESS SYNDROME; IDIOPATHIC PULMONARY FIBROSIS; IN-VIVO; MESSENGER-RNA; P-SELECTIN; RAT; EXPRESSION; INTERLEUKIN-8; CLONING; KC AB Endotoxin-induced lung injury is characterized by neutrophil infiltration of the lungs. The various mechanisms which mediate movement of neutrophils from vascular space to lung interstitium and alveoli remain unclear. Macrophage-inflammatory protein 2 (MIP-2) is a potent chemoattractant for neutrophils and may play a significant role in recruiting neutrophils in acute lung injury in rats. Experiments were performed in male Sprague Dawley rats to: (1) evaluate the kinetics of neutrophil influx in the lung following intraperitoneal administration of Salmonella enteritidis lipopolysaccharide (LPS); (2) determine the expression of transcripts for chemokines and adhesion molecules in the lung following intraperitoneal LPS; and (3) elucidate the effects of intra-alveolar instillation of recombinant rat MIP-2 on neutrophil influx into the lung. Intraperitoneal LPS resulted in an increase in neutrophil sequestration in the lung capillaries of rats as early as 45 min following administration, and there was a parallel increase in lung myeloperoxidase activity. There were also major increases in mRNA in whole-lung homogenates of LPS-treated rats for chemokines MIP-2 and KC (cytokine-induced neutrophil chemoattractant) and adhesion molecules P- and E-selectin at 1 and 2 h following EPS. When recombinant rat MIP-2 was instilled into the alveolar space of rats through a catheter wedged into a bronchus, there was profound neutrophil localization both in the vascular and alveolar space which significantly differed (P < 0.05) from the contralateral lungs of the same animals, and lungs of control animals instilled with control buffer. These observations reveal that MIP-2 is a potent chemoattractant in rat lungs, and suggest that chemoattractants locally released in alveoli can recruit neutrophils to those alveoli. This suggests that alveolar macrophages may play an important role in neutrophil sequestration in sepsis and other inflammatory lung diseases which produce a neutrophilic alveolitis. C1 UNIV VIRGINIA, HLTH SCI CTR, DEPT INTERNAL MED, DIV PULM & CRIT CARE MED, CHARLOTTESVILLE, VA 22908 USA. SCRIPPS RES INST, LA JOLLA, CA USA. NCI, FREDERICK, MD 21701 USA. FU NCI NIH HHS [CA 34546] NR 33 TC 76 Z9 76 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD NOV PY 1996 VL 15 IS 5 BP 656 EP 663 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA VT345 UT WOS:A1996VT34500010 PM 8918372 ER PT J AU Plowe, CV Djimde, A Wellems, TE Diop, S Kouriba, B Doumbo, OK AF Plowe, CV Djimde, A Wellems, TE Diop, S Kouriba, B Doumbo, OK TI Community pyrimethamine-sulfadoxine use and prevalence of resistant Plasmodium falciparum genotypes in Mali: A model for deterring resistance SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID THYMIDYLATE SYNTHASE GENE; DIHYDROFOLATE-REDUCTASE; MOLECULAR-BASIS; MALARIA; CYCLOGUANIL; MUTATIONS; AFRICA AB Pyrimethamine-sulfadoxine (PS, Fansidar(TM); Hoffman-LaRoche, Basel, Switzerland) is now the first-line antimalarial therapy in parts of Africa with high rates of chloroquine-resistant Plasmodium falciparum. With PS resistance increasing and no suitably inexpensive and effective third antimalarial drug available, strategies for delaying the spread of PS resistance in Africa are needed. Community PS usage was measured in two Malian villages, one rural and one periurban, and prevalence of pyrimethamine-resistant P. falciparum genotypes was determined at these sites and two urban sites. The prevalence of resistant genotypes was 22.6% (n = 84) in the periurban village where PS was available from multiple sources and large stocks of PS were observed, and 13.5% (n = 89) and 23.4% (n = 77) in a large town and a city, respectively, where PS is widely available. No pyrimethamine-resistant genotypes (n = 58) were detected in Kolle, a rural village with a community-supported dispensary and clinic where PS is used sparingly and no PS was available in pharmacies or markets. The high rates of pyrimethamine resistant genotypes concurrent with higher PS usage argue for a policy of judicious PS use in Mall and in similar settings. A possible model for slowing the spread of drug-resistant malaria is illustrated by the example of the Kolle clinic. C1 NIAID,PARASIT DIS LAB,MALARIA GENET SECT,NIH,BETHESDA,MD 20892. NATL SCH MED & PHARM,DEPT EPIDEMIOL PARASIT DIS,BAMAKO,MALI. NATL SCH MED & PHARM,MALARIA RES & TRAINING CTR,BAMAKO,MALI. RP Plowe, CV (reprint author), UNIV MARYLAND,SCH MED,DEPT MED,DIV GEOGR MED,CTR VACCINE DEV,685 BALTIMORE ST,HSF 480,BALTIMORE,MD 21201, USA. NR 12 TC 55 Z9 55 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 1996 VL 55 IS 5 BP 467 EP 471 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA VU702 UT WOS:A1996VU70200001 PM 8940973 ER PT J AU Park, CG Park, T Shin, DW AF Park, CG Park, T Shin, DW TI A simple method for generating correlated binary variates SO AMERICAN STATISTICIAN LA English DT Article DE generalized estimating equations; Poisson variables; random number generation ID LONGITUDINAL DATA; MODELS AB Correlated binary data are frequently analyzed in studies of repeated measurements, reliability analysis, and others. In such studies correlations among binary variables are usually nonnegative. This article provides a simple algorithm for generating an arbitrary dimensional random vector of nonnegatively correlated binary variables, Ln some frequently encountered situations the algorithm reduces to explicit expressions. The correlated binary variables are generated from correlated Poisson variables, The key idea lies in the property that any Poisson random variable can be expressed as a convolution of other independent Poisson random variables, The binary variables have desired correlations by sharing common independent Poisson variables. C1 HANKUK UNIV FOREIGN STUDIES,DEPT STAT,SEOUL 449791,SOUTH KOREA. NICHHD,BETHESDA,MD 20892. EWHA WOMANS UNIV,DEPT STAT,SEOUL 120750,SOUTH KOREA. RP Park, CG (reprint author), UNIV SUWON,DEPT APPL STAT,SUWON 445743,SOUTH KOREA. NR 8 TC 86 Z9 86 U1 1 U2 9 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 SN 0003-1305 J9 AM STAT JI Am. Stat. PD NOV PY 1996 VL 50 IS 4 BP 306 EP 310 DI 10.2307/2684925 PG 5 WC Statistics & Probability SC Mathematics GA VZ175 UT WOS:A1996VZ17500005 ER PT J AU Chen, N Chrambach, A AF Chen, N Chrambach, A TI Application of the commercial gel electrophoresis apparatus with intermittent fluorescence scanning to a nonfluorescing protein SO ANALYTICAL BIOCHEMISTRY LA English DT Article AB Gel electrophoretic instrumentation has taken a quantum jump forward with the commercial introduction of an apparatus which, after loading of the sample and initiation of electrophoresis, provides real-time gel patterns at desired time intervals, with a computer printout of mobility values characterizing each band and the means to isolate each desired band with known and maximizeable recovery. However, a major Limitation of that apparatus has been that it employs fluorescence detection and therefore requires the fluorescent labeling of the macromolecules of interest. That limitation was first overcome by E. Gombocz and E. Cortez (Application Note 8, 1994, LabIntelligence, Belmont, CA) in the detection of nonfluorescing carrier ampholytes. in that application, fluorescent, immobile (uncharged) umbelliferone was added to the gel to provide a uniform background of fluorescence upon excitation at 280-360 nm. The isoelectric carrier ampholyte zones could be detected as inverted peaks due to their reduction of the fluorescence intensity of umbelliferone. A similar approach was applied to a representative SDS-protein, conalbumin-SDS, in the present study, replacing umbelliferone in the gel by a fluorescing paper sheet in contact with the lower external surface of the electrophoresis cell. Passage of the proteins reduced the intensity of the light excitation incident on the fluorescent paper so as to decrease the emitted fluorescence signal and allow for the detection of the proteins as ''inverted peaks.'' Presumably, the reduction of background fluorescence is due to the absorbance at 280 nm of the protein passing through the gel, and reduction of the incident Light intensity by that absorbance. The resulting detection of the representative unlabeled SDS-protein by ''fluorescence reduction'' was found to be less sensitive by a factor of 10-20 than detection of the fluorescently labeled protein (at a molar ratio of fluorescein carboxylate to conalbumin of 1/1). The area of the inverted bands of conalbumin-SDS was found to be independent of migration distance. (C) 1996 Academci Press, Inc. RP Chen, N (reprint author), NICHHD,NIH,THEORET & PHYS BIOL LAB,MACROMOL ANAL SECT,BETHESDA,MD 20892, USA. NR 4 TC 13 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD NOV 1 PY 1996 VL 242 IS 1 BP 64 EP 67 DI 10.1006/abio.1996.0428 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA VT729 UT WOS:A1996VT72900010 PM 8923965 ER PT J AU Harlan, WR AF Harlan, WR TI Prevention activities at the National Institutes of Health SO ANNALS OF EPIDEMIOLOGY LA English DT Article RP Harlan, WR (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD NOV PY 1996 VL 6 IS 6 BP 471 EP 473 DI 10.1016/S1047-2797(96)00111-1 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VZ145 UT WOS:A1996VZ14500001 PM 8978875 ER PT J AU Burchfiel, CM Curb, JD Arakaki, R Abbott, RD Sharp, DS Rodriguez, BL Yano, K AF Burchfiel, CM Curb, JD Arakaki, R Abbott, RD Sharp, DS Rodriguez, BL Yano, K TI Cardiovascular risk factors and hyperinsulinemia in elderly men: The Honolulu Heart Program SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Asian Americans; insulin; obesity; risk factors ID INSULIN-RESISTANCE SYNDROME; GLUCOSE-TOLERANCE; PLASMA-INSULIN; FAT DISTRIBUTION; DISEASE RISK; CORONARY; OBESITY; ASCERTAINMENT; HYPERTENSION; INTOLERANCE AB Associations of cardiovascular risk factors, including several measures of adiposity, with hyperinsulinemia were assessed in 3562 elderly (71 to 93 years of age) Japanese American men from the Honolulu Heart Program who were examined between 1991 and 1993. In addition, cardiovascular risk factors measured 25 years earlier were also examined in relation Co hyperinsulinemia. Hyperinsulinemia was defined as fasting insulin greater than or equal to 95th Percentile (20 mu U/mL) among the subset of subjects (n = 504) who were nonobese and free of clinical diabetes and glucose intolerance. When this definition was applied to the entire population, the prevalence of hyperinsulinemia declined cross-sectionally with age (P < 0.001) from 24.2% in men aged 71 to 74 years to 16.4% in men aged 85 Co 93 years. Factors having a positive and independent association with hyperinsulinemia included body mass index (BMI), triglycerides, glucose, hematocrit, use of diabetic medication, heart rate, and hypertension. The association with physical activity was negative. Triglycerides, BMI, diabetic medication, hypertension, and smoking levels measured 25 years earlier were also associated independently with hyperinsulinemia. Associations were similar in nondiabetic subjects. Three measures of adiposity (BMI, waist circumference, and subscapular skinfold thickness) were independently related to hyperinsulinemia cross-sectionally. However, associations involving a difference between the 80th and 20th percentiles in each adiposity measure appeared strongest for BMI (odds ratio (OR) = 4.5, 95% confidence interval (CI) = 3.7 to 5.6) and waist circumference (OR = 4.1, 95% CI = 3.3-5.1) and slightly weaker for subscapular skinfold thickness (OR = 2.1, 95% CI = 1.8-2.5). These findings suggest that features of an insulin resistance syndrome including dyslipidemia, glucose intolerance, hypertension, and obesity, assessed both cross-sectionally and 25 years previously, are associated independently with hyperinsulinemia in elderly Japanese American men. (C) 1996 by Elsevier Science Inc. C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,EPIDEMIOL & BIOMETRY PROGRAM,HONOLULU EPIDEMIOL RES UNIT,HONOLULU,HI 96817. UNIV HAWAII MANOA,JOHN A BURNS SCH MED,DEPT MED,HONOLULU,HI 96822. UNIV HAWAII MANOA,JOHN A BURNS SCH MED,KUAKINI MED CTR,HONOLULU,HI 96822. UNIV VIRGINIA,SCH MED,DIV BIOSTAT,CHARLOTTESVILLE,VA 22908. FU NHLBI NIH HHS [N01-HC-05102] NR 49 TC 25 Z9 28 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 NOV PY 1996 VL 6 IS 6 BP 490 EP 497 DI 10.1016/S1047-2797(96)00103-2 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VZ145 UT WOS:A1996VZ14500005 PM 8978879 ER PT J AU Bowen, D Clifford, CK Coates, R Evans, M Feng, ZD Fouad, M George, V Gerace, T Grizzle, JE Hall, WD Hearn, M Henderson, M Kestin, M Kristal, A Leary, ET Lewis, CE Oberman, A Prentice, R Raczynski, J Toivola, B Urban, N AF Bowen, D Clifford, CK Coates, R Evans, M Feng, ZD Fouad, M George, V Gerace, T Grizzle, JE Hall, WD Hearn, M Henderson, M Kestin, M Kristal, A Leary, ET Lewis, CE Oberman, A Prentice, R Raczynski, J Toivola, B Urban, N TI The women's health trial feasibility study in minority populations: Design and baseline descriptions SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE women's health; minorities; dietary fat; weight; cholesterol; intervention; clinical trial ID LOW-FAT DIET; DENSITY-LIPOPROTEIN CHOLESTEROL; NUTRITION EXAMINATION SURVEYS; NATIONAL-HEALTH; CANCER; HYPERTENSION; PREVENTION; PREVALENCE; PLASMA; ADULTS AB The Women's Health Trial: Feasibility Study in Minority Populations (WHT:FSMP), a randomized trial of 2208 women, was conducted to investigate three questions. First, can women from minority and low-socioeconomic-status populations be recruited in numbers sufficient to evaluate a dietary intervention designed eo lower fat intake. Second, the efficacy of a low fat, increased fruit/vegetable/ grain produce intervention for reducing fat consumption. Third, will participation in the intervention lower plasma cholesterol and estradiol levels relative to the controls. The baseline results showed that an adequate number of minority and low SES women could be recruited to test the study hypotheses. A diverse study population of postmenopausal women consuming a high fat diet was recruited: 28% of participants were Black, 16% were Hispanic, 11% had less than a high school level of education, and 15.5% had household incomes of < $15,000. (C) 1996 by Elsevier Science Inc. C1 EMORY UNIV,SCH MED,ATLANTA,GA. EMORY UNIV,ROLLINS PUBL HLTH,ATLANTA,GA. UNIV ALABAMA,DEPT MED,DIV PREVENT MED,BIRMINGHAM,AL 35294. UNIV MIAMI,DEPT EPIDEMIOL & PUBL HLTH,MIAMI,FL 33152. NCI,BETHESDA,MD 20892. NHLBI,BETHESDA,MD 20892. PACIFIC BIOMETR INC,SEATTLE,WA. UNIV WASHINGTON,DEPT LAB MED,SEATTLE,WA 98195. RP Bowen, D (reprint author), FRED HUTCHINSON CANC RES CTR,DIV PUBL HLTH SCI,CANC PREVENT RES PROGRAM,1124 COLUMBIA ST,MP702,SEATTLE,WA 98104, USA. RI Kristal, Alan/A-8779-2008; OI Kristal, Alan/0000-0002-7329-1617 FU NCI NIH HHS [N01-CN-25426, N01-CN-25425, N01-CN-25427] NR 30 TC 46 Z9 46 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 NOV PY 1996 VL 6 IS 6 BP 507 EP 519 DI 10.1016/S1047-2797(96)00072-5 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VZ145 UT WOS:A1996VZ14500007 PM 8978881 ER PT J AU Tanaka, E Alter, HJ Nakatsuji, Y Shih, JWK Kim, JP Matsumoto, A Kobayashi, M Kiyosawa, K AF Tanaka, E Alter, HJ Nakatsuji, Y Shih, JWK Kim, JP Matsumoto, A Kobayashi, M Kiyosawa, K TI Effect of hepatitis G virus infection on chronic hepatitis C SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID POLYMERASE CHAIN-REACTION; NON-B-HEPATITIS; NON-A; ANTIBODY; THERAPY; RNA; GENOTYPES AB Objective: To clarify the effect of hepatitis G virus (HGV) infection on chronic hepatitis C. Design: Retrospective study. Setting: University hospital in Matsumoto, Japan. Patients: 189 randomly selected patients with histologically proven chronic hepatitis C, including 101 patients receiving interferon-alpha. Measurements: Serum levels of HGV RNA were measured by reverse-transcription polymerase chain reaction. Clinical features, including liver histologic findings, hepatitis C virus (HCV) markers, and response of HCV to interferon-alpha were compared between HGV RNA-positive and HGV RNA-negative patients. Results: 21 of 189 (11%) patients with chronic hepatitis C were positive for HCV RNA. On average, patients with HGV RNA were younger than those without HCV RNA (mean age +/- SD, 46.6 +/- 13.0 years and 51.7 +/- 10.7 years, respectively); other demographic and clinical features were similar. The HCV genotype and HCV RNA level were distributed similarly between patients with and those without HCV infection. Ten of 101 patients with chronic hepatitis C who received interferon-alpha were positive for HCV RNA. The rate of sustained HCV response to intepferon-alpha: in patients with HGV infection (30%) was similar to that in patients without HGV infection (36%). The HGV RNA level decreased during therapy in all 9 patients in whom this value was measured. However, only 2 of these patients had a sustained HGV response after discontinuation of therapy. Conclusions: Patients who only had HCV infection did not differ from patients with HCV and HGV co-infection in clinical presentation, HCV RNA level, or response of HCV to interferon-alpha therapy. Thus, HCV infection had no apparent influence on the clinical or virologic course of HCV, infection. Hepatitis G virus was uniformly sensitive to interferon-alpha therapy, but only a few patients had a sustained virologic response. C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20852. SHINSHU UNIV,SCH MED,DEPT INTERNAL MED 2,MATSUMOTO,NAGANO 390,JAPAN. GENELABS TECHNOL INC,REDWOOD CITY,CA 94063. NR 18 TC 159 Z9 160 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 1 PY 1996 VL 125 IS 9 BP 740 EP 743 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA VQ072 UT WOS:A1996VQ07200006 PM 8929008 ER PT J AU Straus, SE Rooney, JF Hallahan, C AF Straus, SE Rooney, JF Hallahan, C TI Acyclovir suppresses subclinical shedding of herpes simplex virus SO ANNALS OF INTERNAL MEDICINE LA English DT Letter RP Straus, SE (reprint author), NIAID,BETHESDA,MD 20892, USA. NR 2 TC 9 Z9 9 U1 0 U2 1 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 NOV 1 PY 1996 VL 125 IS 9 BP 776 EP 776 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VQ072 UT WOS:A1996VQ07200013 PM 8929015 ER PT J AU Sandor, V Hassan, R Kohn, E AF Sandor, V Hassan, R Kohn, E TI Exacerbation of pseudogout by granulocyte colony-stimulating factor SO ANNALS OF INTERNAL MEDICINE LA English DT Letter RP Sandor, V (reprint author), NCI,BETHESDA,MD 20892, USA. NR 3 TC 8 Z9 8 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 1 PY 1996 VL 125 IS 9 BP 781 EP 781 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VQ072 UT WOS:A1996VQ07200027 PM 8929025 ER PT J AU Lehky, TJ Flerlage, N Katz, D Houff, S Hall, WH Ishii, K Monken, C DhibJalbut, S McFarland, HF Jacobson, S AF Lehky, TJ Flerlage, N Katz, D Houff, S Hall, WH Ishii, K Monken, C DhibJalbut, S McFarland, HF Jacobson, S TI Human T-cell lymphotropic virus type II-associated myelopathy: Clinical and immunologic profiles SO ANNALS OF NEUROLOGY LA English DT Article ID TROPICAL SPASTIC PARAPARESIS; SPONTANEOUS LYMPHOCYTE-PROLIFERATION; INTRAVENOUS-DRUG-USERS; HTLV-II; LEUKEMIA-VIRUS; NEUROLOGICAL DISEASE; HEPATOCELLULAR-CARCINOMA; HEPATITIS-C; PATIENT; INFECTION AB Human T-cell lymphotropic virus type II (HTLV-II) is endemic in several ethnic tribes and among intravenous drug users in metropolitan areas. Despite the presence of HTLV-II in these various populations, the association of HTLV-II with disease is sparse and mainly limited to isolated case reports. This study is an extension of an earlier description of an HTLV-II-infected patient with neurologic disease and presents the clinical and immunologic findings of 4 patients with HTLV-II seropositivity and spastic paraparesis. The patients are of African-American origin with 3 of the patients being of Amerindian descent. All of the patients are seronegative for the human immunodeficiency virus (HIV). The patients progressed to a nonambulatory state in less than 5 years. Magnetic resonance imaging studies obtained from 3 of the patients demonstrated white matter disease in the cerebrum and spinal cord. The cerebrospinal fluid and serum contained antibodies to HTLV-II. The presence of proviral HTLV-II was confirmed by polymerase chain reaction analysis of peripheral blood lymphocytes (PBLs). A spinal cord biopsy from I patient demonstrated HTLV RNA within a lesion. Immunologic studies on 2 patients demonstrated that spontaneous lymphoproliferation of PBLs was present but decreased relative to HTLV-I-infected patients. The clinical and immunologic findings from these HTLV-II-infected patient resemble those found in HTLV-I-associated myelopathy/tropical spastic paraparesis. C1 NINCDS,NEUROIMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. UNIV MARYLAND,DEPT NEUROL,BALTIMORE,MD 21201. VET AFFAIRS MED CTR,DEPT NEUROL,WASHINGTON,DC. ROCKEFELLER UNIV,MED VIROL LAB,NEW YORK,NY 10021. THOMAS JEFFERSON UNIV,PHILADELPHIA,PA 19107. NR 54 TC 30 Z9 30 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 NOV PY 1996 VL 40 IS 5 BP 714 EP 723 DI 10.1002/ana.410400507 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA VX640 UT WOS:A1996VX64000006 PM 8957012 ER PT J AU Dalakas, MC Quarles, RH Farrer, RG Dambrosia, J Soueidan, S Stein, DP Cupler, E Sekul, EA Otero, C AF Dalakas, MC Quarles, RH Farrer, RG Dambrosia, J Soueidan, S Stein, DP Cupler, E Sekul, EA Otero, C TI A controlled study of intravenous immunoglobulin in demyelinating neuropathy with IgM gammopathy SO ANNALS OF NEUROLOGY LA English DT Article ID MONOCLONAL GAMMOPATHY; PARAPROTEINEMIA; DERMATOMYOSITIS; POLYNEUROPATHY; ANTIBODIES; SELECTION; TRIAL; RISK AB Eleven patients with demyelinating polyneuropathy associated with monoclonal IgM antibodies were randomized to receive IVIg or placebo, monthly, for 3 months in a double-blind study. After a washout period, they crossed over to the alternate therapy. Response was gauged by evaluating muscle strength, sensation, and neuromuscular symptoms at baseline, after 3 months, and at treatment's end. After IVIg therapy, the strength improved in only 2 of 11 patients, by 28 and 38.5 points from baseline, and declined after placebo. In 1 other patient, the sensory score improved by 13 points. Antibody titers to MAG/SGPG or gangliosides did not appreciably change. We conclude that Mg has only a modest benefit to not more than 18% of patients with IgM paraproteinemic demyelinating neuropathy. C1 NINCDS, MOL & CELLULAR NEUROBIOL LAB, MYELIN & BRAIN DEV SECT, NIH, BETHESDA, MD USA. RP Dalakas, MC (reprint author), NINCDS, MED NEUROL BRANCH,NEUROMUSCULAR DIS SECT,NIH, BLDG 10,RM 4N248,10 CTR DR, MSC 1382, BETHESDA, MD 20892 USA. NR 19 TC 128 Z9 129 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 1996 VL 40 IS 5 BP 792 EP 795 DI 10.1002/ana.410400516 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA VX640 UT WOS:A1996VX64000015 PM 8957021 ER PT J AU Lush, RM Figg, WD Pluda, JM Bitton, R Headlee, D Kohler, D Reed, E Sartor, O Cooper, MR AF Lush, RM Figg, WD Pluda, JM Bitton, R Headlee, D Kohler, D Reed, E Sartor, O Cooper, MR TI A phase I study of pentosan polysulfate sodium in patients with advanced malignancies SO ANNALS OF ONCOLOGY LA English DT Article DE aPTT; cancer; growth factors; heparan sulfate; heparinoid; pentosan; phase I ID MOLECULAR WEIGHT HEPARIN; POSTOPERATIVE THROMBOEMBOLIC COMPLICATIONS; SULFATED POLYSACCHARIDES; TUMOR-GROWTH; ANTICOAGULANT ACTIVITIES; THROMBOCYTOPENIA; PHARMACOKINETICS; PREVENTION; DEXTRAN-70; INHIBITION AB Background: Pentosan polysulfate (xylanopolyhydrogensulfate) is a semi-synthetic sulfated heparinoid polysaccharide which has been used as an anticoagulant for nearly thirty years in Europe. It antagonizes the binding of bFGF to cell surface receptors and has thus been evaluated for antitumor activity in several animal models and human tumor cell lines. In two angiogenic models pentosan has been shown to inhibit bFGF stimulation of angiogenesis. Previous clinical studies have determined the coagulation effects of pentosan to be the dose-limiting toxicity. Patients and methods: We conducted a phase I study designed to define the duration-limiting toxicity associated with progressive prolongation of a continuous intravenous infusion (three, five, and eight weeks). This study was not designed to escalate the dose of pentosan beyond that required to maintain the activated partial thromboplastin time (aPTT) between 1.8 and 2.2 times the baseline value. Results: Thirteen patients with advanced stage metastatic cancer were enrolled (median age 50 years, range 34 to 61 years). Four patients were treated in cohort #1 (three weeks of infusional therapy), five patients were treated in cohort #2 (five weeks of therapy), and four patients in cohort #3 (eight weeks of therapy). AU patients experienced a progressive prolongation of their aPTT and PT. Furthermore, all patients experienced at least grade I thrombocytopenia. Other complications were, in general, mild. One patient developed grade III liver abnormalities while receiving the eight-week infusion and another patient developed grade IV thrombocytopenia while receiving the same regimen. One patient with colon cancer had stable disease for 24 weeks, while the remaining 12 patients had no objective evidence of response. Conclusion: Pentosan was well tolerated when doses were adjusted for aPTT prolongations and a five-week cycle appeared to be the maximum tolerated duration of infusion (initially 4 mg/kg/day). One patient had stable disease, but there was no objective tumor response noted in the remaining 12 patients. C1 NCI,CLIN PHARMACOL BRANCH,DIV CLIN SCI,BETHESDA,MD 20892. NCI,INVEST DRUG BRANCH,CANC TREATMENT EVALUAT PROGRAM,DIV CANC TREATMENT DIAG & CTR,BETHESDA,MD 20892. NIH,DEPT PHARM,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892. RI Figg Sr, William/M-2411-2016 NR 32 TC 22 Z9 23 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD NOV PY 1996 VL 7 IS 9 BP 939 EP 944 PG 6 WC Oncology SC Oncology GA WC663 UT WOS:A1996WC66300012 PM 9006745 ER PT J AU Kaur, G Sausville, EA AF Kaur, G Sausville, EA TI Altered physical state of p210(bcr-abl) in tyrphostin AG957-treated K562 cells SO ANTI-CANCER DRUGS LA English DT Article DE chronic myelogenous leukemia; Grb2; tyrosine kinase inhibition ID CHRONIC MYELOGENOUS LEUKEMIA; GUANINE-NUCLEOTIDE EXCHANGE; TYROSINE KINASE INHIBITION; EPIDERMAL GROWTH-FACTOR; BCR-ABL ONCOPROTEINS; SIGNAL TRANSDUCTION; ADAPTER PROTEIN; SHC PROTEINS; GRB2; RAS AB AG957 is a tyrosine kinase antagonist which prior studies had shown inhibits p210(bcr-abl), tyrosine kinase activity and K562 chronic myelogenous leukemia cell growth, We report here the effects of AG957 on the physical state of p21(bcr-abl) and its signaling adapter molecules She and Grb2 in K562 cells, After exposure to AG957:, the amount of tyrosine-phosphorylated native p2l0(bcr-abl) decreases, with the appearance of a high molecular weight (> 210 kDa) p210(bcr-abl) This effect is seen after [P-32]orthophosphate and [S-35]methionine labeling, Material suggesting the involvement of p2l0(bcr-abl) in high molecular weight complexes also appears using anti-She, anti-Grb2 and anti-phosphotyrosine antibodies, AG957 also acts in vitro to shift native p2l0(bcr-abl) in anti-p210(bcr-abl) Or anti-Grb2 immunoprecipitates to higher molecular weight forms under conditions where the drug can also act as an antagonist of p210(bcr-abl), autokinase activity. Incubation with dithiothreitol inhibits the appearance of > 210 kDa forms of p2l0(bcr-abl) in the in vitro reaction, These results lead to the hypothesis that AG957 does not act simply as a reversible tyrosine kinase antagonist, but can alter the normal amounts and physical associations of molecules important in tyrosine kinase signaling, These effects likely reflect covalent cross-links induced by the drug. C1 NCI, BIOL CHEM LAB, DIV BASIC SCI, NIH, BETHESDA, MD 20892 USA. NCI, DEV THERAPEUT PROGRAM, DIV CANC TREATMENT DIAGNOSIS & CTR, NIH, BETHESDA, MD 20892 USA. NR 38 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0959-4973 EI 1473-5741 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD NOV PY 1996 VL 7 IS 8 BP 815 EP 824 DI 10.1097/00001813-199611000-00001 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA VY206 UT WOS:A1996VY20600001 PM 8991184 ER PT J AU Leong, SPL Liliental, J Krams, SM Zhou, YM Granberry, ME Martinez, OM AF Leong, SPL Liliental, J Krams, SM Zhou, YM Granberry, ME Martinez, OM TI T cell receptor usage by cytotoxic T lymphocytes against autologous human melanoma SO ANTICANCER RESEARCH LA English DT Article DE TCR; CTL; melanoma ID TUMOR-INFILTRATING LYMPHOCYTES; HUMAN REGRESSIVE MELANOMA; MALIGNANT-MELANOMA; IMMUNE-RESPONSE; METASTATIC MELANOMA; CLONAL EXPANSION; GENE-EXPRESSION; LYMPH-NODE; IN-VIVO; INVITRO AB Background: T cell receptor (TCR) usage by tumor infiltrating lymphocytes (TIL) represents the host's response to autologous melanoma (AM). The goal of this study is to determine TCR usage by cytotoxic T lymphocytes (CTL) against AM. Materials and Methods: CTL were generated from three patients using lymphocytes from metastatic or tumor-draining lymph nodes by repeated in vitro sensitization (IVS). Total RNA was isolated from CTL and reverse-transcribed to cDNA. TCR usage was determined by polymerase chain I eaction (PCR) using TCR primers. Results: Cytolytic activity was non-specific within the first 2-4 weeks following TVS and TCR repertoire in these cultures revealed random V alpha and V beta gene usage. In contrast, by 6-10 weeks of culture, cytolysis was specifically directed against AM cells and such specific cytolysis was significantly correlated with TCR Val (P<0.001). Conclusion: TCR Vol is associated with a common restricted melanoma antigen. C1 NIAID,NIH,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RP Leong, SPL (reprint author), UNIV CALIF SAN FRANCISCO,MT ZION MED CTR,DEPT SURG,POB 7921,SAN FRANCISCO,CA 94120, USA. FU NCI NIH HHS [CA23074] NR 39 TC 2 Z9 2 U1 0 U2 1 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 NOV-DEC PY 1996 VL 16 IS 6B BP 3355 EP 3361 PG 7 WC Oncology SC Oncology GA WB836 UT WOS:A1996WB83600001 PM 9042192 ER PT J AU Schwabe, M Deryugina, EI Bosco, MC Gusella, GL Reinisch, W Kung, HF Bourdon, MA AF Schwabe, M Deryugina, EI Bosco, MC Gusella, GL Reinisch, W Kung, HF Bourdon, MA TI IL-6 signals inhibition of cell adhesion in melanoma A375-C6 SO ANTICANCER RESEARCH LA English DT Article DE extracellular matrix proteins; fibronectin; tenascin; melanoma; adhesion; proliferation; cytokines; interleukin-6 ID EXTRACELLULAR-MATRIX; BREAST-CARCINOMA; GROWTH INHIBITOR; HUMAN TENASCIN; INTERLEUKIN-6; EXPRESSION; INDUCTION; LINES; MICE; DIFFERENTIATION AB IL-6 has been found to be a potent inhibitor of melanoma A375-C6 cell adhesion, in addition to its known action in arresting cells at G(1)/G(0) phase of the cell cycle. IL-6 treated melanoma cells were found to round up and to lose the ability to adhere to fibronectin, laminin, collagen, and tenascin over 72 to 96 hours of lL-6 treatment, a time course similar to that seen for cell cycle inhibition. Cell cycle inhibition and loss of adhesion were found, however, to be independent effects of IL-6. Analysis of cell surface integrins indicated significant changes in the expression of several integrins including downregulation of alpha(2) and alpha(v) beta(5) and upregulation of alpha(3). However, the changes in integrin expression did not correlate with loss of adhesion to relevant ligands. Three A375 melanoma clones varying in metastatic potential also demonstrated inhibition of both cell proliferation and matrix adhesion by IL-6. C1 LA JOLLA INST EXPT MED, LA JOLLA, CA 92037 USA. NCI, FREDERICK CANC RES & DEV CTR, BIOL RESPONSE MODIFIERS PROGRAMME, LAB BIOCHEM PHYSIOL, FREDERICK, MD 21701 USA. NCI, FREDERICK CANC RES & DEV CTR, EXPT IMMUNOL LAB, FREDERICK, MD 21701 USA. RI Bosco, Maria Carla/J-7928-2016 OI Bosco, Maria Carla/0000-0003-1857-7193 FU NCI NIH HHS [CA52879] NR 32 TC 3 Z9 3 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD NOV-DEC PY 1996 VL 16 IS 6B BP 3363 EP 3370 PG 8 WC Oncology SC Oncology GA WB836 UT WOS:A1996WB83600002 PM 9042193 ER PT J AU Vasudevachari, MB Zhang, YM Imamichi, H Imamichi, T Falloon, J Salzman, NP AF Vasudevachari, MB Zhang, YM Imamichi, H Imamichi, T Falloon, J Salzman, NP TI Emergence of protease inhibitor resistance mutations in human immunodeficiency virus type 1 isolates from patients and rapid screening procedure for their detection SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID POLYMERASE CHAIN-REACTION; HIV-1 PROTEASE; ZIDOVUDINE RESISTANCE; REDUCED SENSITIVITY; CROSS-RESISTANCE; DECREASED SENSITIVITY; PCR AMPLIFICATION; RELATIVE AMOUNTS; PROTEINASE; VARIANTS AB Patient human immunodeficiency virus type 1 (HIV-1) isolates that are resistant to protease inhibitors may contain amino acid substitutions L10/V, M46L/I, G48V, L63P, V82A/F/T, I84V, and L90M in the protease gene, Substitutions at positions 82 and/or 90 occur in variants that display high levels of resistance to certain protease inhibitors, Nucleotide substitutions at these two sites also lead to the loss of two HindII restriction enzyme digestion sites, and these changes make possible a rapid procedure for the detection of drug-resistant variants in patients on protease inhibitor therapy, This procedure was used to detect the emergence of mutated viruses at various times after the initiation of therapy with the HIV-I protease inhibitor indinavir, The method includes viral RNA isolation from plasma and reverse transcription PCR amplification of the protease gene with fluorescence-tagged primers. The PCR product is digested with HindII, the cleavage products are separated on a urea-acrylamide gel in a DNA sequencer, and the extent of cleavage is automatically analyzed,vith commercially available software. In viruses from 34 blood samples from four patients, mutations leading to an amino acid change at residue 82 appeared as early as 6 weeks after the start of therapy and persisted throughout the course of the study period (48 weeks), Mutations leading to double substitutions at residues 82 and 90 were seen at a lower frequency and appeared later than the change at position 82, The changes detected by restriction enzyme cleavage were confirmed by DNA sequencing of the cloned protease genes by reverse transcription PCR amplification of viral RNA from isolates in plasma, In addition to the changes at positions 82 and 90, we have identified M46L/I, G48V, and I54V substitutions in isolates derived from indinavir-treated patients, HindII analysis of uncloned, PCR-amplified DNA offers a rapid screening procedure for the detection of virus isolates containing mutations at amino acid residues 82 and 90 in the HIV-1 protease gene, By using other restriction enzymes, the same method can be used to detect additional protease drug-resistant variants and is generally applicable for the detection of mutations. C1 NCI,FREDERICK CANC RES & DEV CTR,LAB MOL RETROVIROL,SAIC FREDERICK,FREDERICK,MD 21702. NIAID,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CO-56000] NR 48 TC 20 Z9 20 U1 0 U2 0 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 NOV PY 1996 VL 40 IS 11 BP 2535 EP 2541 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA VQ870 UT WOS:A1996VQ87000017 PM 8913459 ER PT J AU Becker, ED AF Becker, ED TI Magnetic resonance: An account of some key discoveries and their consequences SO APPLIED SPECTROSCOPY LA English DT Review ID HIGH-RESOLUTION NMR; SOLIDS; SPECTROSCOPY RP Becker, ED (reprint author), NIH, BETHESDA, MD 20892 USA. NR 67 TC 0 Z9 0 U1 0 U2 2 PU SOC APPLIED SPECTROSCOPY PI FREDERICK PA 5320 SPECTRUM DRIVE SUITE C, FREDERICK, MD 21703 USA SN 0003-7028 J9 APPL SPECTROSC JI Appl. Spectrosc. PD NOV PY 1996 VL 50 IS 11 BP A16 EP A28 PG 13 WC Instruments & Instrumentation; Spectroscopy SC Instruments & Instrumentation; Spectroscopy GA VX488 UT WOS:A1996VX48800004 ER PT J AU Zametkin, AJ Schwartz, DJ Ernst, M Cohen, RM AF Zametkin, AJ Schwartz, DJ Ernst, M Cohen, RM TI Is research in normal and ill children involving radiation exposure ethical? Reply SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Letter RP Zametkin, AJ (reprint author), NIMH,SECT CLIN BRAIN IMAGING,BLDG 10,ROOM 4N317,900 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 5 TC 3 Z9 3 U1 0 U2 0 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 NOV PY 1996 VL 53 IS 11 BP 1060 EP 1061 PG 2 WC Psychiatry SC Psychiatry GA VR822 UT WOS:A1996VR82200012 ER PT J AU Murphree, AL Villablanca, JG Deegan, WF Sato, JK Malogolowkin, M Fisher, A Parker, R Reed, E Gamer, CJ AF Murphree, AL Villablanca, JG Deegan, WF Sato, JK Malogolowkin, M Fisher, A Parker, R Reed, E Gamer, CJ TI Chemotherapy plus local treatment in the management of intraocular retinoblastoma SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID CARBOPLATIN; RADIATION; TUMORS; PHARMACOKINETICS; HYPERTHERMIA; ETOPOSIDE; CHILDREN; TOXICITY; LEUKEMIA; THERAPY AB Objective: To describe platinum-based chemotherapy combined with local treatment modalities as an alternative to external beam radiotherapy for intraocular retinoblastoma. Design: Platinum levels st ere measured by atomic absorption analysis in the tumors of 2 patients with retinoblastoma given carboplatin 5 or 2.5 hours before enucleation. Platinum levels in heated vs nonheated Greene melanoma tumors in rabbits were compared. A retrospective review of 172 affected eyes in 136 consecutive patients treated for retinoblastoma between January 1990 and December 1945 was performed. From 1990 to 1992, all treatable eyes initially received systemic carboplatin, 560 mg/m(2), followed by 15 to 30 minutes of continuous diode laser hyperthermia (thermochemotherapy). Since 1992, larger tumors were treated initially with 3 monthly cycles of carboplatin, etoposide, and vincristine sulfate to reduce tumor volume (chemoreduction) followed by sequential aggressive local therapy (SALC) during examinations under anesthesia every 2 to 3 weeks. Outcome Measure: Treatment success was defined as eradication of tumor without enucleation or external beam radiotherapy. Results: Significant therapeutic platinum levels were measured in the human tumors 2.5 and 5 hours after carboplatin administration. Increasing the temperature by 9 degrees C for 15 minutes doubled platinum levers in the rabbit model. Of the 38 eyes with Reese-Ellswosth group 1 through 5b rumors that were treated primarily with thermochemotherapy, all 24 eyes with group 1 and 2 tumors were treated successfully and two of the 4 eyes with group 3 tumors and all 10 eyes with group 5b rumors were treated unsuccessfully. Chemoreduction plus SALT was the primary treatment in 35 eyes and was successful in all 10 eyes with group, 1 through 4 tumors and unsuccessful in all 7 eyes with extensive subretinal seeding and all 18 eyes with group 5b tumors with vitreous seeding. Seventy patients received carboplatin or carboplatin, vincristine, and etoposide, with myelosuppression, occasionally associated with bacteremia, being the main side effect. Transfusions were required in 15% of patients. Radiation retinopathy occurred in all 6 eyes treated with iodine 125 plaques. Conclusions: Thermochemotherapy is successful primary treatment, for Reese-Ellsworth group 1 and 2 retinoblastomas. For larger tumors in the absence of vitreous or Extensive subretinal seeding, 3 cycles of chemoreduction followed by SALT eradicates residual viable tumor. Chemoreduction plus SALT was not successful in eyes with diffuse vitreous or extensive subretinal seeding. Prior chemotherapy increases the risk for radiation retinopathy following I-125 plaque therapy. External beam radiotherapy can safely be avoided in the primary treatment of Reese-Ellsworth groups 1 through 4 nondispersed retinoblastoma. C1 CHILDRENS HOSP LOS ANGELES,CLAYTON OCULAR ONCOL CTR,LOS ANGELES,CA 90027. CHILDRENS HOSP LOS ANGELES,DIV HEMATOL ONCOL,LOS ANGELES,CA 90027. CHILDRENS HOSP LOS ANGELES,DEPT SURG,LOS ANGELES,CA 90027. CHILDRENS HOSP LOS ANGELES,DEPT PEDIAT,LOS ANGELES,CA 90027. UNIV SO CALIF,SCH MED,DEPT OPHTHALMOL,LOS ANGELES,CA. UNIV SO CALIF,SCH MED,DEPT PEDIAT,LOS ANGELES,CA. UNIV SO CALIF,SCH MED,DEPT RADIAT ONCOL,LOS ANGELES,CA. NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. RP Murphree, AL (reprint author), CHILDRENS HOSP LOS ANGELES,DIV OPHTHALMOL,4650 SUNSET BLVD,MS 88,LOS ANGELES,CA 90027, USA. NR 30 TC 256 Z9 272 U1 1 U2 7 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 NOV PY 1996 VL 114 IS 11 BP 1348 EP 1356 PG 9 WC Ophthalmology SC Ophthalmology GA VQ707 UT WOS:A1996VQ70700006 PM 8906025 ER PT J AU Vargas, MP Merino, MJ AF Vargas, MP Merino, MJ TI Infarcted myxoid fibroadenoma following fine-needle aspiration SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID BREAST; BIOPSY; DISPLACEMENT AB Infarction of breast fibroadenomas is very rare and is frequently associated with physiologic changes, such as pregnancy and lactation. We report a case of an infarcted fibroadenoma following fine-needle aspiration. The patient presented with an asymptomatic breast mass, which was clinically difficult to evaluate. Excisional biopsy was performed 7 days after a nondiagnostic fine-needle aspiration of the mass. Microscopically, the nodule showed features of a classic fibroadenoma of the intracanalicular type with myxoid or mucinous stromal changes, as well as extensive areas of acute infarction. This report provides another example of the changes that may be observed in biopsy specimens obtained after fine-needle aspiration of the breast. C1 NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NR 20 TC 11 Z9 11 U1 0 U2 1 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 NOV PY 1996 VL 120 IS 11 BP 1069 EP 1071 PG 3 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA WA371 UT WOS:A1996WA37100017 PM 12049112 ER PT J AU Gut, I Nedelcheva, V Soucek, P Stopka, P Vodicka, P Gelboin, HV IngelmanSundberg, M AF Gut, I Nedelcheva, V Soucek, P Stopka, P Vodicka, P Gelboin, HV IngelmanSundberg, M TI The role of CYP2E1 and 2B1 in metabolic activation of benzene derivatives SO ARCHIVES OF TOXICOLOGY LA English DT Article DE cytochrome P450; benzene; metabolic activation; covalent binding; DNA adducts ID RAT-LIVER MICROSOMES; INDUCIBLE CYTOCHROME-P-450 IIE1; DNA ADDUCT FORMATION; MONOCLONAL-ANTIBODIES; TOLUENE METABOLISM; COVALENT BINDING; NUCLEIC-ACIDS; TOXICITY; ETHANOL; MECHANISM AB CYP2B1 and 2E1 oxidized toluene, aniline and monochlorobenzene (MCB) to water-soluble metabolites and to products covalently binding to microsomal proteins from male Wistar rats at high efficiency. Oxidation of benzene to covalently binding metabolites was catalysed by CYP2B1 and 2E1 more effectively than the formation of water-soluble metabolites, especially at low benzene levels. Thus, the formation of covalently binding products was inversely related but formation of soluble metabolites was proportional to benzene concentration. 1,4-Benzoquinone was responsible for the majority of covalent binding to microsomal proteins, being suppressed by ascorbate; 1,4-semiquinone was not important, since alpha-tocopherol did not inhibit the covalent binding and ESR showed its rapid decay, if NADPH was available. Specific antibodies and inhibitors confirmed the role of CYP2B1 and 2E1 induction. Covalent binding of benzene to DNA was largely due to benzene oxide; similar to 50% was due to N-7 guanine adduct. CYP2E1 oxidizing benzene via phenol to 1,4-hydroquinone appeared to mediate its further oxidation to 1,4-benzoquinone, which also occurred spontaneously, but was reversed in a reducing environment of microsomes with NADPH. Production of OH radicals in microsomes with NADPH was greatly stimulated by HQ and less by BQ, especially in CYP2E1 induced microsomes, although the quinones themselves failed to produce OH radicals. The quinones could act by stimulation of the CYP futile cycle. Therefore, CYP2B1 and 2E1 in rats appeared essential for metabolic activation of benzene derivatives to potentially genotoxic products; BQ dominated the covalent binding of benzene to proteins, whereas DNA adducts were largely due to benzene oxide. C1 NCI,MOL CARCINOGENESIS LAB,BETHESDA,MD 20892. KAROLINSKA INST,BERZELIUS LAB,STOCKHOLM,SWEDEN. RP Gut, I (reprint author), NATL INST PUBL HLTH,SROBAROVA 48,PRAGUE 10042,CZECH REPUBLIC. RI Vodicka, Pavel/H-3370-2014; OI Soucek, Pavel/0000-0002-4294-6799 NR 78 TC 43 Z9 43 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-5761 J9 ARCH TOXICOL JI Arch. Toxicol. PD NOV-DEC PY 1996 VL 71 IS 1-2 BP 45 EP 56 DI 10.1007/s002040050357 PG 12 WC Toxicology SC Toxicology GA WP203 UT WOS:A1996WP20300007 PM 9010585 ER PT J AU Burchfiel, CM Abbott, RD Sharp, DS Curb, JD Rodriguez, BL Yano, K AF Burchfiel, CM Abbott, RD Sharp, DS Curb, JD Rodriguez, BL Yano, K TI Distribution and correlates of lipids and lipoproteins in elderly Japanese-American men - The Honolulu heart program SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE Asian Americans; cardiovascular diseases; cholesterol; lipoproteins; triglycerides ID CARDIOVASCULAR RISK-FACTORS; HIGH-DENSITY-LIPOPROTEIN; HIGH BLOOD CHOLESTEROL; SERUM-LIPIDS; YOUNG-ADULTS; MYOCARDIAL-INFARCTION; ATHEROSCLEROSIS RISK; GLUCOSE-TOLERANCE; PLASMA-FIBRINOGEN; STROKE INCIDENCE AB Adverse lipid and lipoprotein levels are clearly Linked with increased risk of cardiovascular disease in middle age, but evidence in elderly and minority populations is less certain. In this study the distribution and correlates of lipids and lipoproteins were evaluated cross-sectionally in 3044 elderly (71 to 93 years) Japanese-American men from the Honolulu Heart Program who were recently reexamined (1991 to 1993). Mean+/-SD Lipid concentrations were 189+/-33 mg/dL for total cholesterol, 51+/-13 mg/dL for HDL cholesterol, 109+/-31 mg/dL for LDI, cholesterol, and 147+/-89 mg/dL for triglycerides. Prevalence of dyslipidemic patterns was relatively infrequent (total cholesterol greater than or equal to 240 mg/dL: 6.7%; HDL cholesterol <35 mg/dL: 6.4%; LDL cholesterol greater than or equal to 160 mg/dL: 5.5%; triglycerides greater than or equal to 200 mg/dL: 18.7%), while prevalence of desirable total (<200 mg/dL) and HDL cholesterol (greater than or equal to 60 mg/dL) concentrations was more common (62.7% and 23.7%, respectively). Mean levels of total cholesterol. LDL cholesterol, and triglyceride decreased significantly with increasing age (P<.001), while mean HDL cholesterol level increased slightly (P<.05). After univariate analyses of potential correlates, multiple linear regression models were used to identify variables independently associated with each of the lipids. After adjustment for other variables, levels of fibrinogen and hematocrit were positively associated and insulin, white blood cell count, and use of diabetic medication were negatively associated with total cholesterol. Correlates for LDL cholesterol were similar but also included vital capacity (positive relation) and alcohol (negative relation). Heart rate, physical activity, alcohol, and hematocrit were positively associated with HDL cholesterol; body mass index, subscapular skinfold thickness, glucose, fibrinogen, white blood cell count, and hypertension were negatively associated. Factors associated with triglycerides tended to be similar, yet the direction of relations was reversed. Age-adjusted total cholesterol levels were significantly lower in en who had coronary surgery, thromboembolic stroke, and hemorrhagic stroke but were higher in those with peripheral vascular disease. Lower HDL cholesterol levels were found in men with prevalent angina, angioplasty, definite myocardial infarction, thromboembolic stroke, and peripheral vascular disease. LDL cholesterol and triglycerides showed fewer significant relations with these conditions. Findings indicate that elderly Japanese-American men have a favorable lipid profile, except for elevated triglyceride levels, relative to levels in other populations of older Americans and that a number of cardiovascular risk factors and diseases are strongly associated with lipids in elderly men. These analyses also identify several modifiable factors that may favorably influence lipid and lipoprotein levels in the el derry. C1 NHLBI,HONOLULU EPIDEMIOL RES UNIT,FIELD STUDIES & CLIN EPIDEMIOL SCI RES GRP,HONOLULU,HI. UNIV VIRGINIA,SCH MED,DIV BIOSTAT,CHARLOTTESVILLE,VA 22908. UNIV HAWAII MANOA,DIV CLIN EPIDEMIOL,DEPT MED,JOHN A BURNS SCH MED,HONOLULU,HI 96822. 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-05102] NR 62 TC 13 Z9 13 U1 2 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 1996 VL 16 IS 11 BP 1356 EP 1364 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA VT354 UT WOS:A1996VT35400006 PM 8911274 ER PT J AU Reveille, JD Alarcon, GS Fowler, SE Pillemer, SR Neuner, R Clegg, DO Mikhail, IS Trentham, DE Leisen, JCC Bluhm, G Cooper, SM Duncan, H Tuttleman, M Heyse, SP Sharp, JT Tilley, B AF Reveille, JD Alarcon, GS Fowler, SE Pillemer, SR Neuner, R Clegg, DO Mikhail, IS Trentham, DE Leisen, JCC Bluhm, G Cooper, SM Duncan, H Tuttleman, M Heyse, SP Sharp, JT Tilley, B TI HLA-DRB1 genes and disease severity in rheumatoid arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SHARED-EPITOPE HYPOTHESIS; SUSCEPTIBILITY; ASSOCIATION; RA; ALLELES C1 UNIV ALABAMA,DIV CLIN IMMUNOL & RHEUMATOL,BIRMINGHAM,AL 35294. UNIV TEXAS,HLTH SCI CTR,HOUSTON,TX. HENRY FORD HLTH SCI CTR,DETROIT,MI. NIAMS,BETHESDA,MD. NEW YORK HLTH SCI CTR,BROOKLYN,NY. UNIV UTAH,SALT LAKE CITY,UT. BETH ISRAEL HOSP,BOSTON,MA 02215. HENRY FORD HOSP,DETROIT,MI 48202. UNIV VERMONT,COLL MED,BURLINGTON,MA. TIFTON MED CTR,TIFTON,GA. FU NIAMS NIH HHS [N01-AR-1-2205, N01-AR-1-2202, N01-AR-1-2203] NR 19 TC 46 Z9 47 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD NOV PY 1996 VL 39 IS 11 BP 1802 EP 1807 DI 10.1002/art.1780391105 PG 6 WC Rheumatology SC Rheumatology GA VR600 UT WOS:A1996VR60000004 PM 8912501 ER PT J AU Goldman, D Okada, M Lappalainen, J Rotondo, A Malhotra, N Pesonen, U Adamson, M Koulu, M Guenther, D Urbanek, M Long, I Virkkunen, M Ozaki, N Linnoila, M AF Goldman, D Okada, M Lappalainen, J Rotondo, A Malhotra, N Pesonen, U Adamson, M Koulu, M Guenther, D Urbanek, M Long, I Virkkunen, M Ozaki, N Linnoila, M TI The role of murine studies for identifying candidate genes for aggression and other behaviors. SO BEHAVIOR GENETICS LA English DT Meeting Abstract C1 NIAAA,NEUROGENET LAB,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 1996 VL 26 IS 6 BP 586 EP 586 PG 1 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA VY700 UT WOS:A1996VY70000026 ER PT J AU Hamer, DH AF Hamer, DH TI Candidate genes for personality. SO BEHAVIOR GENETICS LA English DT Meeting Abstract C1 NCI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 1996 VL 26 IS 6 BP 586 EP 586 PG 1 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA VY700 UT WOS:A1996VY70000028 ER PT J AU Ogawa, S Lubahn, DB Korach, KS Pfaff, DW AF Ogawa, S Lubahn, DB Korach, KS Pfaff, DW TI Effects of estrogen receptor gene disruption on aggressive behaviors in male mice. SO BEHAVIOR GENETICS LA English DT Meeting Abstract C1 ROCKEFELLER UNIV,NEUROBIOL & BEHAV LAB,NEW YORK,NY 10021. UNIV MISSOURI,DEPT BIOCHEM & CHILD HLTH,COLUMBIA,MO 65211. NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. NR 0 TC 1 Z9 1 U1 1 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 1996 VL 26 IS 6 BP 593 EP 593 PG 1 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA VY700 UT WOS:A1996VY70000057 ER PT J AU Rodriguez, LA Blizard, DA Tarantino, LM McClearn, GE Uhl, GR AF Rodriguez, LA Blizard, DA Tarantino, LM McClearn, GE Uhl, GR TI Interval mapping of QTL in RI mice using the MQTL software package. SO BEHAVIOR GENETICS LA English DT Meeting Abstract C1 NIDA,MOL NEUROBIOL BRANCH,INTRAMURAL RES PROGRAM,BALTIMORE,MD 21224. PENN STATE UNIV,CTR DEV & HLTH GENET,UNIVERSITY PK,PA 16802. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 1996 VL 26 IS 6 BP 595 EP 595 PG 1 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA VY700 UT WOS:A1996VY70000063 ER PT J AU Vandenbergh, DJ Rodriguez, LA Uhl, GR AF Vandenbergh, DJ Rodriguez, LA Uhl, GR TI Genetic analysis of dopamine D4 and D3 receptor genes in a sample of polydrug users. SO BEHAVIOR GENETICS LA English DT Meeting Abstract C1 NIDA,MOL NEUROBIOL BRANCH,INTRAMURAL RES PROGRAM,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 1996 VL 26 IS 6 BP 600 EP 600 PG 1 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA VY700 UT WOS:A1996VY70000082 ER PT J AU Elmer, GI Evans, JL Goldberg, SR Epstein, CJ Cadet, JL AF Elmer, GI Evans, JL Goldberg, SR Epstein, CJ Cadet, JL TI Transgenic superoxide dismutase mice: Increased mesolimbic mu-opioid receptors results in greater opioid-induced stimulation and opioid-reinforced behavior SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE transgenic; superoxide dismutase; mu-opiate receptor; self-administration; sensitization; morphine; mouse ID VENTRAL TEGMENTAL AREA; PROGRESSIVE RATIO SCHEDULE; CENTRAL NERVOUS-SYSTEM; KAINIC ACID LESIONS; NUCLEUS-ACCUMBENS; AUTORADIOGRAPHIC DISTRIBUTION; OPIATE RECEPTORS; DEFICIENT MICE; MORPHINE; COCAINE AB Consequent to the insertion of the human Cu/Zn-superoxide dismutase (SOH) transgene, SOD transgenic mice (SOD-Tg) show higher concentrations of the primary receptor thought to be involved in opioid reinforcement: (mu). These increases are observed in areas specifically associated with the primary neurotransmitter thought to be involved in addiction (dopamine), and in neuroanatomical regions thought: to mediate substance abuse (mesolimbic). In the present study we have tested the idea that these increases in mu-receptors are associated with parallel changes in mu-mediated behaviors. Baseline and morphine-induced locomotor activity were significantly altered in the SOD-Tg mice. A qualitative change in the nature of acute and chronic morphine-induced locomotor activity was demonstrated by a significant change in the slope of the dose-effect curve. SOD-Tg mise were significantly more sensitive to the locomotor stimulant effects of morphine. Intravenous morphine-reinforced behavior was also altered in the SOD-Tg mice, SOD-Tg mice showed significant dose-related changes in operant lever-press responding maintained by morphine injection and significantly greater amounts of behavior were maintained by the drug than by vehicle under an intermittent schedule of reinforcement. In addition, SOD-Tg mice increased operant responding for the drug when the amount of behavior required to maintain drug intake increased 10-fold under a PR schedule of reinforcement. In contrast, in wild-type mice morphine injections failed to maintain greater amounts of behavior than vehicle, there were no dose-related changes in behavior, and when response requirements increased under the PR schedule, morphine intake decreased significantly, Thus, SOD transgene insertion significantly enhanced the efficacy of morphine as a reinforcer. C1 NIDA,ADDICT RES CTR,MOL NEUROPSYCHIAT SECT,NEUROSCI LAB,DIV INTRAMURAL RES,NIH,BALTIMORE,MD 21224. UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,SAN FRANCISCO,CA 94143. RP Elmer, GI (reprint author), NIDA,ADDICT RES CTR,BEHAV PHARMACOL & GENET SECT,PRECLIN PHARMACOL LAB,NIH,BOX 5180,BALTIMORE,MD 21224, USA. NR 74 TC 12 Z9 12 U1 1 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD NOV PY 1996 VL 7 IS 7 BP 628 EP 639 PG 12 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA WN550 UT WOS:A1996WN55000006 ER PT J AU Malabarba, MG Rui, H Deutsch, HHJ Chung, J Kalthoff, FS Farrar, WL Kirken, RA AF Malabarba, MG Rui, H Deutsch, HHJ Chung, J Kalthoff, FS Farrar, WL Kirken, RA TI Interleukin-13 is a potent activator of JAK3 and STAT6 in cells expressing interleukin-2 receptor-gamma and interleukin-4 receptor-alpha SO BIOCHEMICAL JOURNAL LA English DT Article ID IL-2 RECEPTOR; SIGNAL-TRANSDUCTION; TYROSINE KINASE; B-CELLS; JANUS KINASE; BETA-CHAIN; FUNCTIONAL COMPONENT; TRANSCRIPTION FACTOR; T-CELLS; CYTOKINE AB The lymphocyte growth factors interleukin-2 (IL2), IL4, IL7, IL9 and IL15 use the common IL2 receptor-gamma (IL2R gamma) and activate the IL2R gamma-associated tyrosine kinase JAK3 (Janus kinase 3). IL13 is structurally related to IL4, competes with IL4 for binding to cell surface receptors and exhibits many similar biological effects. The molecular basis for this functional overlap between IL4 and IL13 has been attributed mainly to a shared use of the 140 kDa IL4R alpha, since these cytokines appear to be uniquely different in that, according to several recent reports, IL13 does not recruit the IL2R gamma or JAK3. This notion has been supported by the identification of a novel 70 kDa IL13 receptor in certain IL13-responsive cell lines that lack IL2R gamma. The present study sheds new light on the issue of functional overlap between IL13 and IL4, by demonstrating for the first time that, in cells that express both IL2R gamma and IL4R alpha, IL13 can mimic IL4-induced heterodimerization of IL2R gamma and IL4R alpha, with consequent marked activation of JAK3 and the transcription factor STAT6 (IL4-STAT). Reconstitution experiments in BA/F3 cells showed that both cytokines require the simultaneous presence of IL4R alpha and IL2R gamma to mediate JAK3 and proliferative responses, and analysis of 12 IL4R alpha variants showed that IL4 and IL13 signals were equally affected by mutations of the cytoplasmic domain. We conclude that IL13 activates the IL2R gamma-associated JAK3 tyrosine kinase in appropriate cell types, and propose that IL13 is capable of interacting with multiple receptor subunits in a cell-dependent and combinatorial manner. Consequently, we predict that partial disruption of IL13 signal transduction also contributes to the severe combined immunodeficiency syndromes associated with inactivation of the IL2R gamma or JAK3 genes. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,IRSP,SAIC FREDERICK,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,CYTOKINE MOL MECHANISMS SECT,MOL IMMUNOREGULAT LAB,FREDERICK,MD 21702. UNIFORMED SERV UNIV HLTH SCI,F EDWARD HEBERT SCH MED,DEPT PATHOL,TUMOR BIOL PROGRAM,BETHESDA,MD 20814. SANDOZ GMBH,RES INST,A-1235 VIENNA,AUSTRIA. RI Malabarba, Maria Grazia/L-4805-2015 OI Malabarba, Maria Grazia/0000-0002-9457-2047 NR 54 TC 47 Z9 47 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 NOV 1 PY 1996 VL 319 BP 865 EP 872 PN 3 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VT077 UT WOS:A1996VT07700029 PM 8920992 ER PT J AU Degerman, E Belfrage, P Manganiello, VC AF Degerman, E Belfrage, P Manganiello, VC TI cGMP-inhibited phosphodiesterases (PDE3 gene family) SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT 4th IUBMB Conference CY JUL 14-17, 1996 CL EDINBURGH, SCOTLAND ID CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES; CAMP-PHOSPHODIESTERASE; AMP PHOSPHODIESTERASE; SELECTIVE INHIBITOR; MOLECULAR-CLONING; RAT ADIPOCYTES; INSULIN; PHOSPHORYLATION; ACTIVATION; EXPRESSION C1 NIH,NHLBI,PULM CRIT CARE MED BRANCH,BETHESDA,MD 20892. NR 28 TC 22 Z9 24 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD NOV PY 1996 VL 24 IS 4 BP 1010 EP 1014 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VX121 UT WOS:A1996VX12100012 PM 8968502 ER PT J AU Edelstein, SJ Schaad, O Henry, E Bertrand, D Changeux, JP AF Edelstein, SJ Schaad, O Henry, E Bertrand, D Changeux, JP TI A kinetic mechanism for nicotinic acetylcholine receptors based on multiple allosteric transitions SO BIOLOGICAL CYBERNETICS LA English DT Review ID TORPEDO POSTSYNAPTIC MEMBRANES; CHANNEL DOMAIN; CONFORMATIONAL-CHANGES; SYNAPTIC TRANSMISSION; CHOLINERGIC RECEPTORS; FLUORESCENT AGONIST; DESENSITIZATION; GLUTAMATE; NEURONS; MODEL AB Nicotinic acetylcholine receptors are transmembrane oligomeric proteins that mediate interconversions between open and closed channel states under the control of neurotransmitters. Fast in vitro chemical kinetics and in vivo electrophysiological recordings are consistent with the following multi-step scheme. Upon binding of agonists, receptor molecules in the closed but activatable resting state (the Basal state, B) undergo rapid transitions to states of higher affinities with either open channels (the Active state, A) or closed channels (the initial Inactivatable and fully Desensitized states, I and D). In order to represent the functional properties of such receptors, we have developed a kinetic model that links conformational interconversion rates to agonist binding and extends the general principles of the Monod-Wyman-Changeux model of allosteric transitions. The crucial assumption is that the linkage is controlled by the position of the interconversion transition states on a hypothetical linear reaction coordinate. Application of the model to the peripheral nicotinic acetylcholine receptor (nAChR) accounts for the main properties of ligand-gating, including single-channel events, and several new relationships are predicted. Kinetic simulations reveal errors inherent in using the dose-response analysis, but justify its application under defined conditions. The model predicts that (in order to overcome the intrinsic stability of the B state and to produce the appropriate cooperativity) channel activation is driven by an A state with a K-d in the 50 nM range, hence some 140-fold stronger than the apparent affinity of the open state deduced previously. According to the model, recovery from the desensitized states may occur via rapid transit through the A state with minimal channel opening, thus without necessarily undergoing a distinct recovery pathway, as assumed in the standard 'cyclic' model. Transitions to the desensitized states by low concentration 'pre-pulses' are predicted to occur without significant channel opening, but equilibrium values of IC50 can be obtained only with long pre-pulse times. Predictions are also made concerning allosteric effecters and their possible role in coincidence detection. In terms of future developments, the analysis presented here provides a physical basis for constructing more biologically realistic models of synaptic modulation that may be applied to artificial neural networks. C1 UNIV GENEVA, DEPT BIOCHIM, CH-1211 GENEVA 4, SWITZERLAND. INST PASTEUR, F-75734 PARIS 15, FRANCE. NIDDK, CHEM PHYS LAB, NIH, BETHESDA, MD 20892 USA. UNIV GENEVA, DEPT PHYSIOL, CH-1211 GENEVA 4, SWITZERLAND. RI Henry, Eric/J-3414-2013 OI Henry, Eric/0000-0002-5648-8696 NR 107 TC 91 Z9 93 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-1200 J9 BIOL CYBERN JI Biol. Cybern. PD NOV PY 1996 VL 75 IS 5 BP 361 EP 379 DI 10.1007/s004220050302 PG 19 WC Computer Science, Cybernetics; Neurosciences SC Computer Science; Neurosciences & Neurology GA VY701 UT WOS:A1996VY70100001 PM 8983160 ER PT J AU George, MS Ketter, TA Parekh, PI Herscovitch, P Post, RM AF George, MS Ketter, TA Parekh, PI Herscovitch, P Post, RM TI Gender differences in regional cerebral blood flow during transient self-induced sadness or happiness SO BIOLOGICAL PSYCHIATRY LA English DT Article DE positron emission tomography; cerebral blood flow; cingulate; mood disorders; affective illness; affect; sadness; euphoria; emotion; limbic system; gender ID GLUCOSE METABOLIC RATES; SEX-DIFFERENCES; EMISSION TOMOGRAPHY; AFFECTIVE-DISORDERS; AFFECTIVE-ILLNESS; MOOD DISORDERS; HUMAN-BRAIN; PET IMAGES; DEPRESSION; ACTIVATION AB Men, compared to women, are less likely to experience mood disorders, We wondered if gender differences exist in the ability to self-induce transient sadness and happiness, and in regional cerebral blood flow (rCBF) either at rest or during transient emotions, Ten adult men and 10 age-matched women, all healthy and never mentally ill, were scanned using (H2O)-O-15 positron emission tomography at vest and during happy, sad, and neutral states self-induced by recalling affect-appropriate life events and looking at happy, sad or neutral human faces. At rest women had decreased temporal and prefrontal cortex rCBF, and increased brainstem rCBF. There were no significant between-group differences in difficulty, effort required, or the degree of happiness or sadness induced, Women activated a significantly wider portion of their limbic system than did men during transient sadness, despite similar self-reported changes in mood. These findings may aid in understanding gender differences with respect to emotion and mood. (C) 1996 Society of Biological Psychiatry. C1 NIMH,BIOL PSYCHIAT BRANCH,NIH,BETHESDA,MD 20892. NIH,DEPT NUCL MED,POSITRON EMISS TOMOG SECT,BETHESDA,MD 20892. NR 70 TC 166 Z9 170 U1 2 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 1 PY 1996 VL 40 IS 9 BP 859 EP 871 DI 10.1016/0006-3223(95)00572-2 PG 13 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VM694 UT WOS:A1996VM69400006 PM 8896772 ER PT J AU Bronstein, DM Pennypacker, KR Lee, H Hong, JS AF Bronstein, DM Pennypacker, KR Lee, H Hong, JS TI Methamphetamine-induced changes in AP-1 binding and dynorphin in the striatum: Correlated, not causally related events? SO BIOLOGICAL SIGNALS LA English DT Article DE amphetamines; c-Fos; dopamine receptors; gene regulation; opioid peptides; striatum; transcription factors ID RAT PRODYNORPHIN GENE; C-FOS; MESSENGER-RNA; TRANSCRIPTION FACTORS; DOPAMINERGIC SYSTEM; MATRIX COMPARTMENTS; DNA-BINDING; EXPRESSION; NEURONS; COCAINE AB Activation of D-1 dopamine (DA) receptors in the striatum increases the expression of the opioid neuropeptide, dynorphin (DYN). While cAMP is generally accepted as a second messenger in this signal transduction pathway, the role of Fos/FRA proteins and AP-1 binding in mediating D-1 receptor-induced changes in DYN expression remains uncertain. In this study, DYN peptide and mRNA levels, as well as Fos/FRA proteins and AP-1 DNA binding activity, were measured in individual animals following acute challenge with the psychostimulant drug methamphetamine (METH). METH caused an initial decrease in striatal levels of DYN A, reflecting increased peptide release. Six hours postinjection, DYN mRNA levels were significantly elevated by METH as compared to vehicle-injected controls. At the same time, these drugs increased the expression of Fos/FRA-ir proteins, in particular the 35- and 40-kDa molecular weight species, and increased binding to the AP-1 DNA element. Analyses of the time course of METH's effects revealed that DYN mRNA levels, Fos/FRA proteins and AP-1 binding activity showed variable increases by 3 h but all were significantly elevated above control levels by 6 h posttreatment. The D-1-specific antagonist, SCH 23390, completely blocked the METH-induced changes in DYN peptide and mRNA levels while a D-2 receptor antagonist (sulpiride) had little or no effect. These data indicate that stimulant drugs such as METH increase the expression of DYN and AP-1 factors in the striatum via a D-1 receptor-mediated mechanism. However, the finding that AP-1 binding merely paralleled, but did not precede, the increase in DYN expression, as would be expected if it were mediating increased gene transcription, suggests these may be correlative, not causally related events. C1 NIEHS,MOL & INTEGRAT NEUROSCI LAB,NEUROPHARMACOL SECT,RES TRIANGLE PK,NC 27709. RI Pennypacker, Keith/I-5092-2012 NR 49 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1016-0922 J9 BIOL SIGNAL JI Biol. Signals PD NOV-DEC PY 1996 VL 5 IS 6 BP 317 EP 333 PG 17 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WF809 UT WOS:A1996WF80900003 PM 9116798 ER PT J AU Russell, DL Norman, RL Dajee, M Liu, XW Henninghausen, L Richards, JS AF Russell, DL Norman, RL Dajee, M Liu, XW Henninghausen, L Richards, JS TI Prolactin-induced activation and binding of stat proteins to the IL-6RE of the alpha 2-macroglobulin (alpha 2M) promoter: Relation to the expression of alpha 2M in the rat ovary SO BIOLOGY OF REPRODUCTION LA English DT Article ID ACUTE-PHASE RESPONSE; FOLLICLE-STIMULATING HORMONE; MAMMARY EPITHELIAL-CELLS; LUTEINIZING-HORMONE; GROWTH-HORMONE; DNA-BINDING; GENE-EXPRESSION; MESSENGER-RNA; AROMATASE CYTOCHROME-P450; ESTRADIOL BIOSYNTHESIS AB Cellular signaling events by which prolactin (PRL) might regulate gene expression were analyzed in rat ovarian tissues. Whole cell extracts (WCE) were prepared from ovaries of pregnant rats (Days 4, 7, 9-11, 15, 17, and 21) and of hormonally primed (estradiol and FSH) hypophysectomized (H) immature rats before, or 15 min to 24 h after, acute administration of PRL (10 mu g, i.v.). The DNA binding activity in the WCE was analyzed by electrophoretic mobility shift assays using the alpha 2-macroglobulin (alpha 2M) promoter interleukin (IL)-6 response element (IL-6RE) known to confer PRL and IL-6 inducibility to transgenes in target cells, including cultures of luteinized granulosa cells. Injections of PRL stimulated the appearance of a specific binding activity in ovarian extracts of H rats and in corpora lutea and interstitial extracts of pregnant rats from Days 4-9 of pregnancy. The presence of this protein/DNA complex was transient. The greater amount of binding was observed in luteinized tissue and interstitial tissue compared to follicles; and the binding activity contained specific tyrosine phosphorylated Stat (signal transduction and activators of transcription) factors identified by specific antibodies as acute phase response factor (APRF or Stat 3) and mammary gland factor (MCF, or Stat 5 [a and b]). In contrast to the transient activation and appearance of these factors in response to acute PRL treatment as administered to H rats or to pulsatile PRL release as occurs in early pregnancy, elevated levels of the same activated Stat factors were observed in WCE of CL and interstitial tissue prepared at mid-gestation (Days 10-17) when endogenous release of rat placental lactogen (rPL) is chronically elevated in serum. During this period, administration of additional exogenous PRL did not stimulate further activation (binding) of the Stat factors. During luteal regression (Day 21 of gestation) no binding was observed in the absence of PRL, and the response to PRL was markedly diminished despite the constitutive presence of Stat proteins and the Janus kinase that phosphorylates and activates these factors. Elevated binding of these factors to the IL-6RE of the alpha 2M promoter was associated with the expression of alpha 2M mRNA in luteinized granulosa cells and corpora lutea, indicating that activation of Stat factors is one mechanism by which PRL/rPL transactivates the alpha 2M gene in this tissue. C1 BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. NIDDKD,BIOCHEM & METAB LAB,NIH,BETHESDA,MD 20892. RI Russell, Darryl/I-6654-2012 OI Russell, Darryl/0000-0002-4930-7658 NR 60 TC 40 Z9 40 U1 1 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD NOV PY 1996 VL 55 IS 5 BP 1029 EP 1038 DI 10.1095/biolreprod55.5.1029 PG 10 WC Reproductive Biology SC Reproductive Biology GA VN488 UT WOS:A1996VN48800013 PM 8902214 ER PT J AU Chatelier, RC Minton, AP AF Chatelier, RC Minton, AP TI Adsorption of globular proteins on locally planar surfaces: Models for the effect of excluded surface area and aggregation of adsorbed protein on adsorption equilibria SO BIOPHYSICAL JOURNAL LA English DT Article ID LARGE-LIGAND ADSORPTION; MEMBRANES; BINDING AB Equilibrium statistical-thermodynamic models are presented for the surface adsorption of proteins modeled as regular convex hard particles. The adsorbed phase is treated as a two-dimensional fluid, and the chemical potential of adsorbed protein is obtained from scaled particle theory. Adsorption isotherms are calculated for nonassociating and self-associating adsorbing proteins. Area exclusion broadens adsorption isotherms relative to the Langmuir isotherm (negative cooperativity), whereas self-association steepens them (positive cooperativity). The calculated isotherm for adsorption of hard spheres using scaled particle theory for hard discs agrees well with that calculated from the hard disc virial expansion. As the cross section of the adsorbing protein in the plane of the surface becomes less discoidal, the apparent negative cooperativity manifested in the isotherm becomes more pronounced. The model is extended to the case of simultaneous adsorption of a tracer protein at low saturation and a competitor protein with a different size and/or shape at arbitrary fractional saturation. Area exclusion by competitor for tracer (and vice versa) is shown to substantially enhance the displacement of tracer by competitor and to qualitatively invalidate the standard interpretation of ligand competition experiments, according to which the fractional displacement of tracer by competitor is equal to the fractional saturation by competitor. C1 CSIRO,DIV CHEM & POLYMERS,CLAYTON,VIC 3169,AUSTRALIA. NIDDK,SECT PHYS BIOCHEM,BIOCHEM PHARMACOL LAB,NIH,BETHESDA,MD 20892. NR 22 TC 85 Z9 86 U1 0 U2 9 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 1996 VL 71 IS 5 BP 2367 EP 2374 PG 8 WC Biophysics SC Biophysics GA VQ520 UT WOS:A1996VQ52000011 PM 8913577 ER PT J AU Zhou, HX Szabo, A AF Zhou, HX Szabo, A TI Theory and simulation of the time-dependent rate coefficients of diffusion-influenced reactions SO BIOPHYSICAL JOURNAL LA English DT Article ID BROWNIAN DYNAMICS SIMULATIONS; NON-SIMPLE MOLECULES; ORIENTATION CONSTRAINTS; CHRONOAMPEROMETRIC CURRENT; ROTATIONAL DIFFUSION; PROTEIN ASSOCIATION; GENERAL THEORY; KINETICS; ELECTRODES; PARTICLES AB A general formalism is developed for calculating the time-dependent rate coefficient k(t) of an irreversible diffusion-influenced reaction. This formalism allows one to treat most factors that affect k(t), including rotational Brownian motion and conformational gating of reactant molecules and orientation constraint for product formation. At long times k(t) is shown to have the asymptotic expansion k(infinity)[1 + k(infinity)(pi Dt)(-1/2)/4 pi D + ...] where D is the relative translational diffusion constant. An approximate analytical method for calculating k(t) is presented. This is based on the approximation that the probability density of the reactant pair in the reactive region keeps the equilibrium distribution but with a decreasing amplitude. The rate coefficient then is determined by the Green function in the absence of chemical reaction, Within the framework of this approximation, two general relations are obtained. The first relation allows the rate coefficient for an arbitrary amplitude of the reactivity to be found if the rate coefficient for one amplitude of the reactivity is is known. The second relation allows the rate coefficient in the presence of conformational gating to be found from that in the absence of conformational gating. The ratio k(t)/k(0) is shown to be the survival probability of the reactant pair at time t starting from an initial distribution that is localized in the reactive region. This relation forms the basis of the calculation of k(t) through Brownian dynamic's simulations. Two simulation procedures involving the propagation of nonreactive trajectories initiated only from the reactive region are described and illustrated on a model system. Both analytical and simulation results demonstrate the accuracy of the equilibrium-distribution approximation method. C1 NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. RP Zhou, HX (reprint author), HONG KONG UNIV SCI & TECHNOL,DEPT BIOCHEM,CLEAR WATER BAY,KOWLOON,HONG KONG. RI Szabo, Attila/H-3867-2012; Zhou, Huan-Xiang/M-5170-2016 OI Zhou, Huan-Xiang/0000-0001-9020-0302 NR 41 TC 68 Z9 69 U1 2 U2 14 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 1996 VL 71 IS 5 BP 2440 EP 2457 PG 18 WC Biophysics SC Biophysics GA VQ520 UT WOS:A1996VQ52000018 PM 8913584 ER PT J AU Leikin, S Kozlov, MM Fuller, NL Rand, RP AF Leikin, S Kozlov, MM Fuller, NL Rand, RP TI Measured effects of diacylglycerol on structural and elastic properties of phospholipid membranes SO BIOPHYSICAL JOURNAL LA English DT Article ID STRONGLY CURVED MONOLAYERS; BILAYER-MEMBRANES; NEUTRAL SURFACE; WATER-SYSTEMS; FUSION; TRANSITIONS; LAMELLAR; MODULI; PHASE AB Diacylglycerol, a biological membrane second messenger, is a strong perturber of phospholipid planar bilayers. It converts multibilayers to the reverse hexagonal phase (H-II), composed of highly curved monolayers. We have used x-ray diffraction and osmotic stress of the H-II phase to measure structural dimensions, spontaneous curvature, and bending moduli of dioleoylphosphatidylethanolamine (DOPE) monolayers doped with increasing amounts of dioleoylglycerol (DOG). The diameter of the H-II phase cylinders equilibrated in excess water decreases significantly with increasing DOG content, Remarkably, however, all structural dimensions at any specific water/lipid ratio that is less than full hydration are insensitive to DOG, By plotting structural parameters of the H-II phase with changing water content in a newly defined coordinate system, we show that the elastic deformation of the lipid monolayers can be described as bending around a pivotal plane of constant area, This dividing surface includes 30% of the lipid volume independent of the DOG content (polar heads and a small fraction of hydrocarbon chains), As the mole fraction of DOG increases to 0.3, the radius of spontaneous curvature defined for the pivotal surface decreases from 29 Angstrom to 19 Angstrom, and the bending modulus increases from similar to 11 to 14 (+/- 0.5)kT. We derive the conversion factors and estimate the spontaneous curvatures and bending moduli for the neutral surface which, unlike the pivotal plane parameters, are intrinsic properties that apply to other deformations and geometries. The spontaneous curvature of the neutral surface differs from that of the pivotal plane by less than 10%, but the difference in the bending moduli is up to 40%. Our estimate shows that the neutral surface bending modulus is similar to 9kT and practically does not depend on the DOG content. C1 TEL AVIV UNIV,SACKLER FAC MED,DEPT PHYSIOL & PHARMACOL,IL-69978 RAMAT AVIV,ISRAEL. BROCK UNIV,DEPT BIOL SCI,ST CATHARINES,ON L2S 3A1,CANADA. RP Leikin, S (reprint author), NIH,DIV COMP RES & TECHNOL,STRUCT BIOL LAB,BLDG 12A,RM 2041,BETHESDA,MD 20892, USA. RI Leikin, Sergey/A-5518-2008 OI Leikin, Sergey/0000-0001-7095-0739 NR 25 TC 149 Z9 150 U1 2 U2 20 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 1996 VL 71 IS 5 BP 2623 EP 2632 PG 10 WC Biophysics SC Biophysics GA VQ520 UT WOS:A1996VQ52000034 PM 8913600 ER PT J AU Brenner, B Xu, S Chalovich, JM Yu, LC AF Brenner, B Xu, S Chalovich, JM Yu, LC TI Radial equilibrium lengths of actomyosin cross-bridges in muscle SO BIOPHYSICAL JOURNAL LA English DT Article ID RELAXED FIBER STIFFNESS; RABBIT PSOAS MUSCLE; FORCE GENERATION; F-ACTIN; PARALLEL INHIBITION; ATPASE ACTIVITY; SKINNED FIBERS; RIGOR MUSCLE; CALDESMON; BINDING AB Radial equilibrium lengths of the weakly attached, force-generating, and rigor cross-bridges are determined by recording their resistance to osmotic compression, Radial equilibrium length is the surface-to-surface distance between myosin and actin filaments at which attached cross-bridges are, on average, radially undistorted, We previously proposed that differences in the radial equilibrium length represent differences in the structure of the actomyosin cross-bridge. Until now the radial equilibrium length had only been determined for various strongly attached cross-bridge states and was found to be distinct for each state examined, In the present work, we demonstrate that weakly attached cross-bridges, in spite of their low affinity for actin, also exert elastic forces opposing osmotic compression, and they are characterized by a distinct radial equilibrium length (12.0 nm vs, 10.5 nm for force-generating and 13.0 nm for rigor cross-bridge), This suggests significant differences in the molecular structure of the attached cross-bridges under these conditions, e.g., differences in the shape of the myosin head or in the docking of the myosin to actin. Thus, the present finding supports our earlier conclusion that there is a structural change in the attached cross-bridge associated with the transition from a weakly bound configuration to the force-generating configuration, The implications for imposing spatial constraints on modeling actomyosin interaction in the filament lattice are discussed. C1 NIAMSD,NIH,BETHESDA,MD 20892. HANNOVER MED SCH,D-3000 HANNOVER,GERMANY. E CAROLINA UNIV,SCH MED,GREENVILLE,NC 27834. OI Chalovich, Joseph/0000-0002-1243-4055 NR 29 TC 19 Z9 19 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 1996 VL 71 IS 5 BP 2751 EP 2758 PG 8 WC Biophysics SC Biophysics GA VQ520 UT WOS:A1996VQ52000046 PM 8913612 ER PT J AU Beckwith, M Jorgensen, G Longo, DL AF Beckwith, M Jorgensen, G Longo, DL TI The protein product of the proto-oncogene c-cbl forms a complex with phosphatidylinositol 3-kinase p85 and CD19 in anti-IgM-stimulated human B-lymphoma cells SO BLOOD LA English DT Article ID TYROSINE PHOSPHORYLATION; LYMPHOCYTES-B; KINASE-C; RECEPTOR STIMULATION; V-CBL; ACTIVATION; SRC; PROTOONCOGENE; BINDING; TRANSLOCATION AB Multiple signal transduction cascades, consisting of multiple interacting proteins, are activated following stimulation through most cell surface receptors, including the immunoglobulin receptor of B lymphocytes. In this report, we investigated the multimolecular complexes formed following anti-Ig stimulation of a human B-lymphoma cell line, resulting in activation of phosphatidylinositol 3-kinase (PI3K). PI3K is a lipid kinase that consists of an 85-kD regulatory subunit, bound to a 110-kD catalytic subunit. CD19 is a 95-kD B-cell surface marker that contains a consensus binding motif for PI3Kp85 in the cytoplasmic domain and recruits PI3K activity in activated B cells. The protein product of the c-cbl protooncogene is a 129-kD protein that is expressed in early B-lineage cells and in myeloid cells and is phosphorylated on tyrosine following receptor-mediated signaling in T and B lymphocytes, We demonstrate here that phosphorylated c-cbl complexes with CD19 and with PI3Kp85 via its C-terminal SH2 domain, and that both c-cbl and CD19 are associated with active PI3K in anti-Ig-stimulated cells, Although we cannot differentiate between a three-component, c-cbl/CD19/p85 complex and individual two-component complexes, these studies suggest that c-cbl may function as a docking protein, possibly linking distinct signal transduction pathways. C1 NIA, GERONTOL RES CTR, BALTIMORE, MD 21224 USA. RP Beckwith, M (reprint author), NCI, FREDERICK CANC RES & DEV CTR,SAIC, INTRAMURAL RES SUPPORT PROGRAM,BLDG 567, ROOM 206, FREDERICK, MD 21702 USA. NR 33 TC 20 Z9 20 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 1996 VL 88 IS 9 BP 3502 EP 3507 PG 6 WC Hematology SC Hematology GA VP736 UT WOS:A1996VP73600026 PM 8896416 ER PT J AU Kohno, Y Ji, XD Mawhorter, SD Koshiba, M Jacobson, KA AF Kohno, Y Ji, XD Mawhorter, SD Koshiba, M Jacobson, KA TI Activation of A(3) adenosine receptors on human eosinophils elevates intracellular calcium SO BLOOD LA English DT Article ID GUINEA-PIG EOSINOPHILS; MAJOR BASIC-PROTEIN; MOLECULAR-CLONING; BRONCHIAL-ASTHMA; HISTAMINE-RELEASE; HUMAN LUNG; LEUKOTRIENES; THYMOCYTES; METABOLISM; MECHANISMS AB Adenosine (ADO) is a potent bronchoconstrictor in allergic patients and has been shown to increase the release of histamine from human lung tissues, Antagonists of ADO A(1) and A(2A) receptors are not effective in attenuating these effects. Therefore, involvement of ADO A(3) receptors in the bronchoconstrictor and/or inflammatory effects have to be considered, Eosinophils also play a pivotal role in allergic diseases such as asthma, thus it is natural to consider a link between the A(3) receptor and eosinophils, Human peripheral blood eosinophils express the ADO A(3) receptor as indicated by detection of the transcript for A(3) receptors in polymerase chain reaction-amplified cDNA derived from the cells. A(3) receptors on eosinophil membranes were characterized using the A(3) receptor agonist radioligand I-125-labeled AB-MECA, which yielded B-max and K-d values of 1.31 pmol/mg protein and 3.19 nmol/L, respectively. Treatment of eosinophils with the highly potent and selective A(3) receptor agonist CI-IB-MECA clearly induced Ca2+ release from intracellular Ca2+ pools followed by Ca2+ influx, suggesting the presence of phospholipase C-coupled A(3) receptors. In contrast, the ADO receptor agonists CPA and CGS 21680, selective for A(1) and A(2a) receptors, respectively, at concentrations of less than or equal to 30 pmol/L did not elevate the intracellular Ca2+ level, These results attest to the existence of ADO A(3) receptors on eosinophils and suggest that ADO stimulates these cells to release Ca2+ from intracellular stores via the activation of A(3) receptors. (C) 1996 by The American Society of Hematology. C1 NIDDK,NIH,MOL RECOGNIT SECT,LAB BIOORGAN,LAB PARASIT DIS,BETHESDA,MD 20892. NIAID,NIH,IMMUNOL LAB,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z99 DK999999, Z01 DK031117-20] NR 39 TC 94 Z9 97 U1 1 U2 2 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 NOV 1 PY 1996 VL 88 IS 9 BP 3569 EP 3574 PG 6 WC Hematology SC Hematology GA VP736 UT WOS:A1996VP73600035 PM 8896425 ER PT J AU Corina, D Bavelier, D Jezzard, P Clark, V Padmanhaban, S Rauschecker, J Braun, A Turner, R Neville, H AF Corina, D Bavelier, D Jezzard, P Clark, V Padmanhaban, S Rauschecker, J Braun, A Turner, R Neville, H TI Processing of American Sign Language and English in native deaf signers: An fMRI study at 4T. SO BRAIN AND COGNITION LA English DT Meeting Abstract C1 UNIV OREGON,EUGENE,OR 97403. UNIV WASHINGTON,SEATTLE,WA 98195. NIMH,BETHESDA,MD 20892. INST NEUROL,LONDON WC1N 3BG,ENGLAND. RI Turner, Robert/C-1820-2008; Rauschecker, Josef/A-4120-2013 NR 0 TC 0 Z9 0 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 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD NOV PY 1996 VL 32 IS 2 BP 10 EP 10 PG 2 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA VZ841 UT WOS:A1996VZ84100005 ER PT J AU Bavelier, D Corina, D Jezzard, P Clark, V Karni, A Padmanhaban, S Rauschecker, J Turner, R Neville, H AF Bavelier, D Corina, D Jezzard, P Clark, V Karni, A Padmanhaban, S Rauschecker, J Turner, R Neville, H TI Sentence reading: An fMRI study at 4T SO BRAIN AND COGNITION LA English DT Article; Proceedings Paper CT TENNET VII - Theoretical and Experimental Neuropsychology CY AUG 14-16, 1996 CL UNIV QUEBEC MONTREAL, MONTREAL, CANADA HO UNIV QUEBEC MONTREAL ID LANGUAGE AB In this study blood flow was monitored while monolingual right handed subjects read English sentences. Our results confirm the role of the left perisylvian cortex in language processing. However, individual subject analyses reveal a pattern of activation characterized by several, small, limited patches rather than a few large anatomically well-circumscribed centers. Between-subject analyses confirm a lateralized pattern of activation, indicate as active classical language areas such as Broca's, Wernicke's and the angular gyrus, and also point to areas only more recently considered as language-relevant including the anterior portion of the superior temporal lobe and the dorsolateral prefrontal cortex. C1 UNIV WASHINGTON,DEPT PSYCHOL,SEATTLE,WA 98195. NIMH,BETHESDA,MD 20892. INST NEUROL,LONDON WC1N 3BG,ENGLAND. RP Bavelier, D (reprint author), UNIV OREGON,HEDCO NEUROSCI BLDG 2520,EUGENE,OR 97403, USA. RI Turner, Robert/C-1820-2008; Rauschecker, Josef/A-4120-2013; OI Clark, Vincent/0000-0002-9151-2102 NR 6 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 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD NOV PY 1996 VL 32 IS 2 BP 165 EP 167 PG 3 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA VZ841 UT WOS:A1996VZ84100034 ER PT J AU Wanderley, MI NegroVilar, A AF Wanderley, MI NegroVilar, A TI Pretreatment with phorbol ester and an LHRH agonist reduces testosterone production and protein kinase C activity in rat Leydig cells challenged with PDBu and LHRH SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Article DE Leydig cells; protein kinase C activity; PDBu; LHRH; testosterone; [D-Ala(6), Des-Gly(10)]-LHRH ethylamide ID GONADOTROPIN-RELEASING HORMONE; DIFFERENTIAL DOWN-REGULATION; STEROIDOGENESIS; ACTIVATION; TISSUE; TESTIS AB We have investigated the role of protein kinase C (PK-C) in luteinizing hormone-releasing hormone (LHRH)-induced testosterone secretion from purified rat Leydig cells (70-80-day old Sprague-Dawley rats) by pretreating the cells in vitro with 200 mM phorbol 12,13-dibutyrate (PDBu) (a known procedure to down-modulate this enzyme in most cell types) and 1 mu M [D-Ala(6),Des-Gly(10)]-LHRH ethylamide, an LHRH agonist (LHRH-A). Following pretreatment we measured PK-C activity and secretion of testosterone in response to subsequent challenges with the PK-C activator PDBu (20-2000 nM) and with LHRH (0.001-1.0 mu M) and the Ca2+-mobilizing secretagogue A(23187) (0.1-100 mu M) in the same cell preparation. PDBu and LHRH-A pretreatments caused a reduction in testosterone secretion in response to subsequent exposure to PDBu or LHRH. Both pretreatments decreased PK-C activity in crude and purified extracts of the same cells, The magnitude of reduction of the secretory response was greater than that of enzyme activity for both PDBu and LHRH-A pretreatment (68.9% reduction of testosterone secretion vs 54.7% reduction of PK-C activity in PDBu-pretreated cells and 78.6% reduction of testosterone production vs 36.6% reduction of PK-C activity in LHRH-A-pretreated cells). The effect of phorbol ester pretreatment on PDBu- or LHRH-stimulated testosterone secretion and PK-C activity was specific (no measurable effect with 4 alpha-PDBu, an inactive phorbol ester). While PDBu and LHRH-A pretreatment reduced Leydig cell responsiveness to PDBu or LHRH, the secretion of testosterone in response to the Ca2+-mobilizing secretagogue A(23187) was similar in PDBu- and LHRH-A-pretreated and in control (non-pretreated) cells. We conclude that down-modulation of protein kinase C by prolonged exposure of Leydig cells to phorbol esters or LHRH-A results in decreased PK-C activity and testosterone secretion. These results provide the first evidence that pretreatment with LHRH-A, which does not enter the cell, can affect the steroidogenesis and PK-C activity responses to PDBu (the intracellular ligand of PK-C). C1 NIEHS, MOL & INTEGRAT NEUROSCI LAB, REPROD NEUROENDOCRINOL SECT, RES TRIANGLE PK, NC 27709 USA. NR 30 TC 9 Z9 9 U1 0 U2 0 PU ASSOC BRAS DIVULG CIENTIFICA PI SAO PAULO PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, 00, BRAZIL SN 0100-879X EI 1678-4510 J9 BRAZ J MED BIOL RES JI Brazilian J. Med. Biol. Res. PD NOV PY 1996 VL 29 IS 11 BP 1557 EP 1565 PG 9 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA VR615 UT WOS:A1996VR61500024 PM 9196561 ER PT J AU Stein, U Walther, W Shoemaker, RH AF Stein, U Walther, W Shoemaker, RH TI Modulation of mdr1 expression by cytokines in human colon carcinoma cells: An approach for reversal of multidrug resistance SO BRITISH JOURNAL OF CANCER LA English DT Article DE multidrug resistance; reversal; cytokine; colon carcinoma cell ID P-GLYCOPROTEIN EXPRESSION; TUMOR-NECROSIS-FACTOR; ALPHA-INTERFERON; DRUG SENSITIVITY; LINES; GENE; DOXORUBICIN; CANCER; ANTITUMOR; GROWTH AB Reversal of multidrug resistance (MDR) may offer a means of increasing the effectiveness of tumour chemotherapy. A variety of recent evidence indicates that cytokines may be particularly useful in this endeavour. To investigate the molecular mechanism by which cytokines may sensitise multidrug-resistant colon carcinoma cells, HCT15 and HCT116, to treatment with MDR-related drugs, we evaluated the effects of the human cytokines tumour necrosis factor alpha (TNF alpha), interleukin 1 (IL-2) and interferon gamma (IFN gamma) on mdr1 gene expression at the mRNA level by reverse transcription - polymerase chain reaction (RT-PCR) and at the protein level with monoclonal antibodies by immune flow cytometry. P-glycoprotein function was examined after accumulation of the fluorescent drug, doxorubicin, by how cytometry. Chemosensitivity to doxorubicin and vincristine was analysed using the XTT assay. All three cytokines were found to modulate the MDR characteristics on mdr1 expression levels, P-glycoprotein function and measured chemosensitivity to MDR-associated anti-cancer drugs. This cytokine-induced reversal of MDR was strongly time dependent, with maximal effects after 48 and 72 h of cytokine treatment. If similar modulation of MDR phenotype can be obtained in in vivo models, it may be possible to verify the time course for modulation by cytokine treatment and to design appropriate clinical trials of this strategy for MDR reversal. C1 NCI,LAB DRUG DISCOVERY RES & DEV,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT,FREDERICK,MD 21702. NR 39 TC 57 Z9 74 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 NOV PY 1996 VL 74 IS 9 BP 1384 EP 1391 DI 10.1038/bjc.1996.553 PG 8 WC Oncology SC Oncology GA VP315 UT WOS:A1996VP31500010 PM 8912533 ER PT J AU Hewitt, RE AF Hewitt, RE TI High endothelial cell proliferation index and high microvessel density in vascular hotspots suggest an active angiogenic process in human colorectal adenocarcinomas - Reply SO BRITISH JOURNAL OF CANCER LA English DT Letter RP Hewitt, RE (reprint author), NCI,PATHOL LAB,NIH,BLDG 10,RM BIB58,10 CTR DR MSC 1500,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 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 NOV PY 1996 VL 74 IS 9 BP 1507 EP 1507 DI 10.1038/bjc.1996.575 PG 1 WC Oncology SC Oncology GA VP315 UT WOS:A1996VP31500032 ER PT J AU Brooks, DJ Woodward, S Thompson, FH DosSantos, B Russell, M Yang, JM Guan, XY Trent, J Alberts, DS Taetle, R AF Brooks, DJ Woodward, S Thompson, FH DosSantos, B Russell, M Yang, JM Guan, XY Trent, J Alberts, DS Taetle, R TI Expression of the zinc finger gene EVI-1 in ovarian and other cancers SO BRITISH JOURNAL OF CANCER LA English DT Article DE zinc finger; ovarian cancer; EVI-1 ID MYELOID-TRANSFORMING GENE; CARCINOMA CELL-LINE; DNA-BINDING; HER-2/NEU EXPRESSION; RECEPTOR ANTIBODIES; SEQUENCE; PROTEIN; TRANSLOCATIONS; LEUKEMIA; PROTOONCOGENE AB The EVI-1 gene was originally detected as an ectopic viral insertion site and encodes a nuclear zinc finger DNA-binding protein. Previous studies showed restricted EVI-1 RNA or protein expression during ontogeny; in a kidney and an edometrial carcinoma cell line; and in normal murine oocytes and kidney cells. EVI-1 expression was also detected in a subset of acute myeloid leukaemias (AMLs) and myelodysplasia. Because EVI-1 is expressed in the urogenital tract during development, we examined ovarian cancers and normal ovaries for EVI-1 RNA expression using reverse transcription-polymerase chain reaction (RT-PCR) and RNAase protection. Chromosome abnormalities were examined using karyotypes and whole chromosome 3 and 3q26 fluorescence in situ hybridisation (FISH). RNA from six primary ovarian tumours, five normal ovaries and 47 tumour cell lines (25 ovarian, seven melanoma, three prostate, seven breast and one each of bladder, endometrial, lung epidermoid and histiocytic lymphoma) was studied. Five of six primary ovarian tumours, three of five normal ovaries and 22 of 25 ovarian cell lines expressed EVI-1 RNA. A variety of other non-haematological cancers also expressed EVI-1 RNA. Immunostaining of ovarian cancer cell lines revealed nuclear EVI-1 protein. In contrast, normal ovary stained primarily within oocytes and faintly in stroma. Primary ovarian tumours showed nuclear and intense, diffuse cytoplasmic staining. Quantitation of EVI-1 RNA, performed using RNAase protection, showed ovarian carcinoma cells expressed 0 to 40 times the EVI-1 RNA in normal ovary, and 0-6 times the levels in leukaemia cell lines. Southern analyses of ovarian carcinoma cell lines showed no amplification or rearrangements involving EVI-1. In some acute leukaemias, activation of EVI-1 transcription is associated with translocations involving 3q26, the site of the EVI-1 gene. Ovarian carcinoma karyotypes showed one line with quadruplication 3(q24q27), but no other clonal structural rearrangements involving 3q26. However, whole chromsome 3 and 3q26 FISH performed on lines with high EVI-1 expression showed translocations involving chromosome 3q26. EVI-1 is overexpressed in ovarian cancer compared with normal ovaries, suggesting a role for EVI-1 in solid tumour carcinogenesis or progression. Mechanisms underlying EVI-1 overexpression remain unclear, but may include rearrangements involving chromosome 3q26. C1 UNIV ARIZONA,DEPT MED,TUCSON,AZ 85724. UNIV ARIZONA,DEPT PATHOL,TUCSON,AZ 85724. UNIV ARIZONA,DEPT PHARMACOL,TUCSON,AZ 85724. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP Brooks, DJ (reprint author), ARIZONA CANC CTR,HEMATOL ONCOL SECT,1515 N CAMPBELL AVE,POB 245024,TUCSON,AZ 85724, USA. RI Guan, Xin-Yuan/A-3639-2009 OI Guan, Xin-Yuan/0000-0002-4485-6017 FU NCI NIH HHS [CA41183, CA23074] NR 52 TC 45 Z9 47 U1 1 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD NOV PY 1996 VL 74 IS 10 BP 1518 EP 1525 DI 10.1038/bjc.1996.583 PG 8 WC Oncology SC Oncology GA VR947 UT WOS:A1996VR94700003 PM 8932329 ER PT J AU Ungar, S VandeMeeren, A Tammilehto, L Linnainmaa, K Mattson, K Gerwin, BI AF Ungar, S VandeMeeren, A Tammilehto, L Linnainmaa, K Mattson, K Gerwin, BI TI High levels of MDM2 are not correlated with the presence of wild-type p53 in human malignant mesothelioma cell lines SO BRITISH JOURNAL OF CANCER LA English DT Article DE tumour suppressor; mesothelioma; carcinogenesis ID RETINOBLASTOMA SUSCEPTIBILITY GENE; AUTOREGULATORY FEEDBACK LOOP; SOFT-TISSUE SARCOMAS; TRANSCRIPTIONAL ACTIVITY; EPITHELIAL-CELLS; GROWTH-FACTORS; HUMAN CANCER; T-ANTIGEN; PROTEIN; EXPRESSION AB Prior analysis of 20 human mesothelioma cell lines for p53 status revealed only two mutations and one p53 null cell line, although p53 expression was detected in most cell lines. In addition, mRNA and protein expression of the retinoblastoma gene product in human mesothelioma cell lines is similar to normal controls. We have tested for p53 induction after exposure to ionising radiation and demonstrate this induction and, to a lesser extent, p21(WAFI) induction, in both normal mesothelial cells and p53-positive mesothelioma cell lines. We postulated that high levels of MDM2 might alter p53 and retinoblastoma tumour-suppressor function in mesothelioma. However, Southern blot analysis for mdm2 indicated that no amplification had occurred in 18 mesothelioma cell lines tested. Steady-state mRNA and protein levels also did not indicate overexpression. These results indicate that high levels of MDM2 are not responsible for inactivating the functions of wild-type p53 or the retinoblastoma gene product during the pathogenesis of malignant mesothelioma. C1 NCI,DIV BASIC SCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. IPSN,DPHD,SECT AUTONOME RADIOBIOL APPL MED,F-92265 FONTENAY ROSES,FRANCE. UNIV HELSINKI HOSP,INST EPIDEMIOL & BIOSTAT,HELSINKI 00290,FINLAND. INST OCCUPAT HLTH,SF-00250 HELSINKI,FINLAND. UNIV HELSINKI,DEPT PULM MED,HELSINKI 00290,FINLAND. NR 67 TC 24 Z9 24 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 NOV PY 1996 VL 74 IS 10 BP 1534 EP 1540 DI 10.1038/bjc.1996.585 PG 7 WC Oncology SC Oncology GA VR947 UT WOS:A1996VR94700005 PM 8932331 ER PT J AU Torrey, EF AF Torrey, EF TI First-rank symptoms or rank-and-file symptoms? Commentary SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Editorial Material RP Torrey, EF (reprint author), NIMH,NEUROPSYCHIAT RES HOSP,2700 MARTIN LUTHER KING JR AVE SE,WASHINGTON,DC 20032, USA. NR 0 TC 0 Z9 0 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 NOV PY 1996 VL 169 IS 5 BP 543 EP 543 PG 1 WC Psychiatry SC Psychiatry GA VR105 UT WOS:A1996VR10500005 ER PT J AU Brinton, LA AF Brinton, LA TI Hormones and risk of cancers of the breast and ovary SO CANCER CAUSES & CONTROL LA English DT Editorial Material ID ESTROGEN RP Brinton, LA (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 20 TC 9 Z9 9 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 NOV PY 1996 VL 7 IS 6 BP 569 EP 571 DI 10.1007/BF00051697 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA VQ340 UT WOS:A1996VQ34000001 PM 8932915 ER PT J AU Bowden, CJ Figg, WD Dawson, NA Sartor, O Bitton, RJ Weinberger, MS Headlee, D Reed, E Myers, CE Cooper, MR AF Bowden, CJ Figg, WD Dawson, NA Sartor, O Bitton, RJ Weinberger, MS Headlee, D Reed, E Myers, CE Cooper, MR TI A phase I/II study of continuous infusion suramin in patients with hormone-refractory prostate cancer: Toxicity and response SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE suramin; prostate cancer; toxicity; pharmacokinetics; adaptive control with feedback; concentration controlled trial; flutamide; flutamide withdrawal ID FLUTAMIDE WITHDRAWAL; ADAPTIVE-CONTROL; GROWTH-FACTOR; DRUG; VARIABLES; CARCINOMA; FEEDBACK; THERAPY; INVITRO; AIDS AB Introduction: Suramin is a synthetic polysulfonated naphthylurea which has been used for the treatment of African trypanosomiasis and onchocerciasis, but since the mid-1980s has received attention as a possible antiretroviral and antineoplastic agent. Objective: This clinical trial of suramin was undertaken as a phase I/II study in patients with hormone-refractory prostate cancer,with the hypothesis that the intensity of therapy with suramin could be increased significantly if measures were undertaken to maintain the plasma concentrations of the drug under 300 mu g/ml. Methods: We report the clinical results of this trial, wherein patients were treated at three different targeted plasma suramin concentrations (275, 215 and 175 mu g/ml) for varying periods of time (2, 4 or 8 weeks), with delivery of the drug by continuous intravenous infusion. Results: The major toxicity observed in this trial was neurologic, consisting of a motor and sensory peripheral neuropathy that resulted in both paresis and paralysis of the limbs. Nearly all of this severe (CTEP grade III, IV) neurologic toxicity was observed in the patients treated at a plasma suramin concentration of 275 mu g/ml for 4 or more weeks. A single patient treated at 215 mu g/ml for 8 weeks developed moderate (CTEP grade III) proximal lower extremity weakness, and no patient treated at 175 mu g/ml developed this toxicity. The second most common toxicity observed was infection of the central venous catheter. The overall response rate for all of the evaluable patients was 17% (13 of 75 patients). In addition, prostate-specific antigen (PSA)-defined responses were observed in six patients receiving therapy at 175 mu g/ml, but these responses were confounded by cessation of therapy with flutamide during suramin treatment. Conclusions: In summary, although plasma suramin concentrations were maintained below 300 mu g/ml, neurologic toxicity nonetheless occurred with high frequency in patients treated at 275 mu g/ml for 4 or more weeks. Therapy at 215 and 175 mu g/ml was in general well tolerated, but central Venous catheter-related infection, as well as the inconvenience and expense of continuous infusional therapy, make this method of drug delivery impractical. Only moderate antitumor activity was observed during this trial, but it is possible that both continuation of flutamide and flutamide withdrawal during suramin therapy confounded the assessment of suramin's activity in hormone-refractory prostate cancer. C1 NCI,CLIN PHARMACOL BRANCH,CLIN ONCOL PROGRAM,DIV CANC TREATMENT,BETHESDA,MD 20892. RI Figg Sr, William/M-2411-2016 NR 24 TC 26 Z9 26 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD NOV-DEC PY 1996 VL 39 IS 1-2 BP 1 EP 8 DI 10.1007/s002800050531 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA VW720 UT WOS:A1996VW72000001 PM 8995493 ER PT J AU Elizondo, FG Sung, C AF Elizondo, FG Sung, C TI Effect of angiotensin II on immunotoxin uptake in tumor and normal tissue SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE immunotoxin; angiotensin II; biodistribution ID INTERSTITIAL FLUID PRESSURE; BLOOD-FLOW; MONOCLONAL-ANTIBODY; SOLID TUMORS; MACROMOLECULES; HYPERTENSION; ENHANCEMENT; XENOGRAFTS; TRANSPORT; KINETICS AB Purpose: To investigate the effect of the sarcosine analog of human angiotensin II ({sar}ATII) on the uptake and spatial distribution of immunotoxins (MW 210000 Da) in RD rhabdomyosarcoma xenografts in mice. This analog has a presser activity similar to native angiotensin II (ATII) but a longer duration of action. Method: A period of elevated blood pressure of approxi mately 80 min, measured by noninvasive photoplethysmography, was achieved by a 40-min continuous i.p. infusion of {sar}ATII at 0.07 mu g/min. Tumor-bearing animals were injected i.v. with I-125-labeled specific and I-131-labeled nonspecific immunotoxins and made hypertensive by i.p. infusion of {sar}ATII. Radioactivity was measured in plasma, tumor, liver, kidney and muscle at 2, 6 and 24 h. Plasma radioactivity was subtracted from tissue values to calculate tissue uptake. To assess the spatial distribution of immunotoxin in the solid tumor, I-125-labeled specific immunotoxin was injected i.v. into tumor-bearing animals, and quantitative autoradiography was performed on tumor sections. Results: The uptake of specific or nonspecific immunotoxins in tumor and normal tissues was not significantly different in {sar}ATII-hypertensive animals compared with saline-treated controls. In control animals, the spatial distribution of I-125-labeled specific immunotoxins was very heterogeneous and contained punctate accumulations throughout the tumor. Treatment with {sar}ATII did not affect this distribution qualitatively or quantitatively. To examine a possible reason for the lack of {sar}ATII effect, we measured the interstitial pressure of the RD tumor using a fluid-filled micropipette connected to a servo-null pressure transducer. The interstitial pressure in this solid tumor was unexpectedly low, only 0.6+/-0.9 mm Hg. Conclusions: The sustained period of {sar}ATII-induced hypertension had no effect on RD tumor or normal tissue uptake or tumor spatial distribution of immunotoxin. In saline-treated controls, the heterogeneity of immunotoxin distribution does not arise from an elevated interstitial pressure. Further studies are needed to determine whether a correlation exists between responsiveness to ATII-induced hypertensive chemotherapy using macromolecular drugs and tumor type and/or physiological properties. C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NR 38 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD NOV-DEC PY 1996 VL 39 IS 1-2 BP 113 EP 121 DI 10.1007/s002800050546 PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA VW720 UT WOS:A1996VW72000016 PM 8995508 ER PT J AU Volpe, DA Tomaszewski, JE Parchment, RE Garg, A Flora, KP Murphy, MJ Grieshaber, CK AF Volpe, DA Tomaszewski, JE Parchment, RE Garg, A Flora, KP Murphy, MJ Grieshaber, CK TI Myelotoxic effects of the bifunctional alkylating agent bizelesin on human, canine and murine myeloid progenitor cells SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE comparative; CFU-gm; in vitro; bizelesin; clonal assays ID INTERSTRAND CROSS-LINKING; ANTI-TUMOR AGENT; PHASE-I; DNA; CC-1065; U-73,975; U-77,779; FCE-24517; BINDING; ANALOG AB Bizelesin is a potent synthetic derivative of the anticancer agent CC-1065 that preferentially alkylates and binds the minor grove of DNA. Preclinical animal studies have found bizelesin to be more toxic to beagle dogs than to rodents and that myelosuppression was the dose-limiting toxicity. This toxicity was dose- and time-dependent in all species. Due to the significant difference in the in vivo myelotoxicity between species, it was important to determine which one most closely resembles humans on a pharmacodynamic basis. Therefore, hematopoietic clonal assays were utilized to evaluate the effects of bizelesin on granulocyte-macrophage (CFU-gm) colony formation. Marrow cells were exposed in vitro to bizelesin (0.001-1000 nM) for 1 or sh and then assayed for colony formation. There was a 3-log difference in drug concentration at which 100% colony inhibition occurred (1 or 8 h) for murine CFU-gm versus human or canine CFU-gm. The IC70 value after an 8-h bizelesin exposure for human CFU-gm (0.006 +/- 0.002 nM) was 2220-times lower than for murine CFU-gm (13.32 +/- 8.31 nM). At any given concentration, an 8 h drug exposure resulted in greater colony inhibition than a 1 h exposure for all species (P < 0.05). Increasing exposure time from 1 to 8 h increased toxicity to human and canine CFU-gm much more than to murine CFU-gm. The clinically formulated drug solution was a more potent inhibitor of human colony formation than drug dissolved in DMSO. The IC70 value after a 1-h exposure was 1.7 times lower for human CFU-gm with formulated bizelesin (0.106 +/- 0.105 nM) than bulk drug in DMSO (0.184 +/- 0.044 nM). The results of these in vitro clonal assays were qualitatively consistent with those seen in whole animal studies, suggesting that bizelesin will be a potent myelosuppressive agent in the clinic. Since the dose-limiting toxicity in preclinical models is myelosuppression and the in vitro sensitivity of human and canine CFU-gm is similar, the canine maximum tolerated dose (MTD) is better than the murine MTD to determine a safe starting dose for phase I clinical trials. C1 NCI,TOXICOL & PHARMACOL BRANCH,BETHESDA,MD 20892. HIPPLE CANC RES CTR,DAYTON,OH. RP Volpe, DA (reprint author), US FDA,DIV RES & TESTING,MOD-1 BLDG,ROOM 2009,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. FU NCI NIH HHS [N01-CM-37834] NR 24 TC 43 Z9 43 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD NOV-DEC PY 1996 VL 39 IS 1-2 BP 143 EP 149 DI 10.1007/s002800050550 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA VW720 UT WOS:A1996VW72000020 PM 8995512 ER PT J AU Hsing, AW AF Hsing, AW TI Essential fatty acids and prostate cancer: An emerging hypothesis? SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID RISK; DIET; INHIBITORS; CELL RP Hsing, AW (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,EXECUT PLAZA NORTH 415,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 24 TC 10 Z9 10 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 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 1996 VL 5 IS 11 BP 859 EP 860 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA VR596 UT WOS:A1996VR59600001 PM 8922291 ER PT J AU Cooper, GS Kamel, F Sandler, DP Davey, FR Bloomfield, CD AF Cooper, GS Kamel, F Sandler, DP Davey, FR Bloomfield, CD TI Risk of adult acute leukemia in relation to prior immune-related conditions SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NON-HODGKINS-LYMPHOMA; RHEUMATOID-ARTHRITIS; MULTIPLE-MYELOMA; MEDICAL CONDITIONS; YORKSHIRE; HISTORY; CANCER AB We explored the association between immune-related conditions and adult acute leukemia in a study of 624 patients with acute myeloid leukemia (AML), 124 patients with acute lymphoblastic leukemia (ALL), 63 patients with other acute leukemias, and 637 healthy population controls, Common childhood viral diseases were weakly associated with AML and ALL, particularly with early exposure (less than or equal to 5 years of age), Odds ratios (ORs) were elevated for chicken pox and measles at any age, but only the associations with measles were statistically significant [OR = 1.89; 95% confidence interval (CI), 1.40-2.56 for AML and OR = 1.81; 95% CI, 1.07-3.06 for ALL]. There was no association between other infectious diseases, allergies, asthma, or eczema and risk for AML or ALL, although there was a significant association between psoriasis and ALL (OR = 3.23; 95% CI, 1.25-8.30). These results offer little support for either a protective effect of enhanced immune surveillance or a harmful effect from antigenic stimulation in relation to risk for acute leukemia in adults, However, the associations between cancer risk and childhood infectious diseases are intriguing and may warrant additional research. C1 SUNY HLTH SCI CTR,DEPT PATHOL,SYRACUSE,NY 13210. ROSWELL PK CANC INST,DEPT MED,BUFFALO,NY 14263. RP Cooper, GS (reprint author), NIEHS,EPIDEMIOL BRANCH A3 05,ENVIRONM & MOL EPIDEMIOL SECT,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Kamel, Freya/0000-0001-5052-6615; Sandler, Dale/0000-0002-6776-0018 FU NCI NIH HHS [CA 37027, CA 37055, CA 31946] NR 23 TC 24 Z9 25 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 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 1996 VL 5 IS 11 BP 867 EP 872 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA VR596 UT WOS:A1996VR59600003 PM 8922293 ER PT J AU White, JD Johnson, JA Nam, JM Cranston, B Hanchard, B Waldmann, TA Manns, A AF White, JD Johnson, JA Nam, JM Cranston, B Hanchard, B Waldmann, TA Manns, A TI Distribution of human leukocyte antigens in a population of black patients with human T-cell lymphotrophic virus type I-associated adult T-cell leukemia/lymphoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HTLV-I; LEUKEMIA-LYMPHOMA; HLA; JAMAICAN AB Human leukocyte antigens (HLAs) play an important role in regulating the immune response to infectious agents and determinants of malignant transformation, We compared the HLA frequencies of 25 black patients with adult T-cell leukemia/lymphoma (ATL) referred to the National Cancer Institute for therapy with a racially similar, asymptomatic control population of human T-cell lymphotrophic virus, type I (HTLV-I)-seropositive individuals (n = 45), Serological typing was performed for MHC class I and II antigens. Antigen frequencies were calculated, and corresponding gene frequencies were estimated using the maximum likelihood method. Comparisons between the ATL and control group were made with chi(2) or Fisher's exact test. Three antigens (A36, B18, and DR53) were found to have a higher frequency in the ATL patients than in the controls (uncorrected two-tailed P < 0.05). The gene frequencies for these antigens also were statistically significant in the uncorrected analysis, However, only A36 approached statistical significance after correction of the P value for multiple comparisons (P = 0.08). The results of this pilot study indicate that black patients with ATL may have increased frequencies of certain class I HLA when compared with a racially similar HTLV-I-positive reference population. This suggests that either these antigens may represent markers for a population at greater risk of developing ATL once infected with HTLV-I or that they were acquired at some point in the process of malignant transformation or progression from the carrier state to onset of ATL. These antigens should be targeted in larger studies to confirm or refute these findings. C1 NCI,NIH,DIV CANC EPIDEMIOL & GENET,BIOSTAT & VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. UNIV W INDIES,DEPT PATHOL,KINGSTON 7,JAMAICA. RP White, JD (reprint author), NCI,METAB BRANCH,BLDG 10,ROOM 4N115,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CP-31006] NR 29 TC 11 Z9 11 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 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 1996 VL 5 IS 11 BP 873 EP 877 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA VR596 UT WOS:A1996VR59600004 PM 8922294 ER PT J AU Wu, AH Ziegler, RG HornRoss, PL Nomura, AMY West, DW Kolonel, LN Rosenthal, JF Hoover, RN Pike, MC AF Wu, AH Ziegler, RG HornRoss, PL Nomura, AMY West, DW Kolonel, LN Rosenthal, JF Hoover, RN Pike, MC TI Tofu and risk of breast cancer in Asian-Americans SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID IN-VITRO; WOMEN; DIET; PHYTOESTROGENS; SOY; GENISTEIN; SHANGHAI; PROFILES; LIGNANS; CELLS AB Breast cancer rates among Asian-Americans are lower than those of US whites but considerably higher than rates prevailing in Asia, It is suspected that migration to the US brings about a change in endocrine function among Asian women, although reasons for this change remain obscure, The high intake of soy in Asia and its reduced intake among Asian-Americans has been suggested to partly explain the increase of breast cancer rates in Asian-Americans. We conducted a population-based case-control study of breast cancer among Chinese-, Japanese-, and Filipino-American women in Los Angeles County MSA, San Francisco Oakland MSA, and Oahu, Hawaii, Using a common questionnaire which assessed frequency of intake of some 90 food items, 597 Asian-American women (70% of those eligible) diagnosed with incident, primary breast cancer during 1983-1987 and 966 population-based controls (75% of those eligible) were interviewed, Controls were matched to cases on age, ethnicity, and area of residence, This analysis compares usual adult intake of soy (estimated primarily from tofu intake) among breast cancer cases and control women, After adjustment for age, ethnicity and study area, intake of tofu was more than twice as high among Asian-American women born in Asia (62 times per year) compared to those born in the US (30 times per year), Among migrants, intake of tofu decreased with years of residence in the US, Risk of breast cancer decreased with increasing frequency of intake of tofu after adjustment for age, study area, ethnicity, and migration history; the adjusted OR associated with each additional serving per week was 0.85 (95% CI = 0.74-0.99), The protective effect of high tofu intake was observed in pre- and postmenopausal women. This association remained after adjustment for selected dietary factors and menstrual and reproductive factors. However, this study was not designed specifically to investigate the role of soy intake and our assessment of soy intake may be incomplete, We cannot discount the possibility that soy intake is a marker of other protective aspects of Asian diet and/or Asian lifestyle. C1 NCI, ENVIRONM EPIDEMIOL BRANCH, DIV CANC ETIOL, BETHESDA, MD 20892 USA. NO CALIF CANC CTR, UNION CITY, CA 94587 USA. UNIV HAWAII, CANC RES CTR HAWAII, PROGRAM EPIDEMIOL, HONOLULU, HI 96817 USA. WESTAT CORP, ROCKVILLE, MD 20892 USA. RP Wu, AH (reprint author), UNIV SO CALIF, KENNETH NORRIS JR COMPREHENS CANC CTR, DEPT PREVENT MED, 1441 EASTLAKE AVE MS 44, LOS ANGELES, CA 90033 USA. NR 34 TC 244 Z9 253 U1 3 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 1996 VL 5 IS 11 BP 901 EP 906 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA VR596 UT WOS:A1996VR59600008 PM 8922298 ER PT J AU McShane, LM Dorgan, JF Greenhut, S Damato, JJ AF McShane, LM Dorgan, JF Greenhut, S Damato, JJ TI Reliability and validity of serum sex hormone measurements SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID POSTMENOPAUSAL WOMEN; REPRODUCIBILITY; ESTRADIOL; ESTROGENS; CANCER; MEN AB The laboratory reliability and validity of sex hormone measurements were examined at multiple levels, including lower levels characteristic of children and postmenopausal women. Serum was drawn from four adult male and four adult female healthy volunteers, From each individual's serum pool, a medium- and a low-dilution pool were created. Biochemical analyses for total and non-sex hormone-binding globulin (SHBG)bound estradiol, estrone, estrone sulfate, progesterone, and SHBG were performed on female samples. Male samples were analyzed for total and non-SHBG-bound testosterone, dihydrotestosterone, androstenedione, and dehydroepiandrosterone sulfate. Two aliquots from each pool were assayed twice in each of two labs, All assays except SHBG in one lab used RTA procedures. Reliability was assessed by variance components analyses and estimated coefficients of variation (CVs). Validity was assessed by comparing observed measurements versus expected values based on known dilution ratios. For the testosterone and dihydrotestosterone assays, CVs were usually less than 10%, For estradiol and progesterone, CVs were usually less than 15%. Assays with larger estimated CVs included androstenedione, dehydroepiandrosterone sulfate, estrone, and estrone sulfate. Absolute levels differed markedly between labs for most assays. Observed measurements generally agreed with values expected from the dilution ratios. A notable exception was the estrone assay at the loa est dilution level, where observed measurements were 2-4 times those expected. A similar but less pronounced overestimation bias for the low levels of estradiol was also suggested. This intra- and interlaboratory variability and apparent low dilution overestimation should be accounted for in studies relating hormones to cancer risk, especially those involving children and postmenopausal women. C1 NCI,CANC PREVENT STUDIES BRANCH,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. MCKESSON BIOSERV,ROCKVILLE,MD 20850. RP McShane, LM (reprint author), NCI,BIOMETR RES BRANCH,CTEP,DCTDC,EXECUT PLAZA NORTH,ROOM 739,6130 EXECUT BLVD MSC,BETHESDA,MD 20892, USA. RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 14 TC 30 Z9 30 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 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 1996 VL 5 IS 11 BP 923 EP 928 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA VR596 UT WOS:A1996VR59600012 PM 8922302 ER PT J AU Li, ZW Shanmugam, N Katayose, D Huber, B Cowan, K Seth, P AF Li, ZW Shanmugam, N Katayose, D Huber, B Cowan, K Seth, P TI Enzyme/prodrug gene therapy approach for breast cancer using a recombinant adenovirus expression Escherichia coli cytosine deaminase SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 NCI,MED BREAST CANC SECT,MED BRANCH,NIH,BETHESDA,MD 20892. GLAXO WELLCOME INC,DIV PHARMACOL,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV-DEC PY 1996 VL 3 IS 6 SU S BP P81 EP P81 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA WC571 UT WOS:A1996WC57100081 ER PT J AU Polymeropoulos, MH Ide, SE Becker, K Naylor, SL AF Polymeropoulos, MH Ide, SE Becker, K Naylor, SL TI Linkage and cytogenetic mapping of a CAG repeat containing human cDNA to 3p24.2-p22 SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID HOMOZYGOUS DELETION; TRIPLET REPEAT; HUMAN-DISEASE; FRAGILE-X; INSTABILITY; MUTATIONS; REGION; GENE; EXPANSION; ATROPHY AB A trinucleotide (CAG)n repeat containing cDNA was isolated from a human cDNA library and sequenced. The locus tvas mapped by Linkage analysis in the CEPH families and by cytogenetic analysis to 3p24.2-p22. We have additionally excluded this gene as a candidate for small cell lung carcinoma by the analysis of cell lines carrying homozygous deletions for the 3p chromosomal region. (C) Elsevier Science Inc., 1996 C1 NINCDS,NATL INST HLTH,BETHESDA,MD 20892. UNIV TEXAS,HLTH SCI CTR,DEPT CELLULAR & STRUCT BIOL,SAN ANTONIO,TX 78284. RP Polymeropoulos, MH (reprint author), NATL CTR HUMAN GENOME RES,LAB GENET DIS RES,BLDG 49,RM 4A66,BETHESDA,MD 20892, USA. NR 18 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 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD NOV PY 1996 VL 92 IS 1 BP 46 EP 49 DI 10.1016/S0165-4608(96)00148-3 PG 4 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA VX048 UT WOS:A1996VX04800012 PM 8956871 ER PT J AU Hodge, JW AF Hodge, JW TI Carcinoembryonic antigen as a target for cancer vaccines SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE anti-idiotype; recombinant poxviruses; polynucleotide immunization; carcinoembryonic antigen; immunotherapy; cancer vaccines ID POLYNUCLEOTIDE VACCINE; GENE FAMILY; ANTIIDIOTYPE ANTIBODY; ANTITUMOR-ACTIVITY; ADHESION MOLECULE; IMMUNE-RESPONSE; VIRUS-VACCINE; IMMUNOTHERAPY; CEA RP Hodge, JW (reprint author), NATL CANC INST, TUMOR IMMUNOL & BIOL LAB,NIH,BLDG 10,ROOM 8B07, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 NR 38 TC 60 Z9 64 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 EI 1432-0851 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD NOV PY 1996 VL 43 IS 3 BP 127 EP 134 DI 10.1007/s002620050313 PG 8 WC Oncology; Immunology SC Oncology; Immunology GA VZ393 UT WOS:A1996VZ39300002 PM 9001565 ER PT J AU Shibata, MA Ward, JH Devor, DE Liu, ML Green, JE AF Shibata, MA Ward, JH Devor, DE Liu, ML Green, JE TI Progression of prostatic intraepithelial neoplasia to invasive carcinoma in C3(1)/SV40 large T antigen transgenic mice: Histopathological and molecular biological alterations SO CANCER RESEARCH LA English DT Article ID STEROID-BINDING-PROTEIN; CELLULAR TUMOR-ANTIGEN; RAS ONCOGENE MUTATIONS; IN-SITU HYBRIDIZATION; ALLELIC LOSS; SUPPRESSOR GENE; FREQUENT LOSS; C-3 GENES; P53 GENE; CANCER AB The progression of prostatic intraepithelial neoplasia (PIN) to invasive prostate carcinoma has been analyzed in the C3(1)T-AG transgenic mouse model and appears very similar to the process proposed to occur in humans, PIN lesions in these transgenic mice histologically resemble those found in human PIN, Low-grade PIN was observed in the ventral and dorsolateral lobes at 2 months of age, whereas high-grade PIN was found in both lobes by 5 months of age, A progressive increase in the number of PIN lesions was observed with age. Prostate carcinomas, which appeared to arise from PIN lesions, mere found by 7 months of age in the venll al lobe and 11 months of age in the dorsolateral lobe. Expression of T-AG mRNA and protein in these lesions correlated with the development of PIN and carcinomas, as did the overexpression of p53 protein, Apoptosis levels were quite low in normal epithelial cells, moderate in low grade PLY, and high in high-grade PIN and carcinomas. Levels of expression of proliferating cell nuclear antigen correlated with the degree of severity of the prostate lesions. Eighteen % of PIN lesions were found to already; harbor Ha-ras mutations, whereas 33% of carcinomas showed various mutations in Ha-ras, Ki-ras, and/or p53. Mutations in Ha-ras may, there fore, be an early event in a significant portion of PIN lesions, Because high-grade PIN showed many characteristics similar to those observed in carcinomas and high-grade PIN was often found contiguous to carcinomas, we conclude that high-grade PIN is a precursor lesion of prostate carcinoma in this transgenic model. These transgenic mice will be useful to study mechanisms responsible for the progression of invasive carcinomas from PIN precursor lesions, as may occur during the development of prostate cancer in humans. C1 NCI,FREDERICK CANC RES & DEV CTR,MOL ONCOL LAB,NIH,DIV BASIC SCI,FREDERICK,MD 21702. NCI,VET & TUMOR PATHOL SECT,OFF LAB ANIM SCI,FREDERICK,MD 21702. NR 43 TC 79 Z9 79 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1996 VL 56 IS 21 BP 4894 EP 4903 PG 10 WC Oncology SC Oncology GA VP486 UT WOS:A1996VP48600015 PM 8895741 ER PT J AU Risio, M Lipkin, M Newmark, H Yang, K Rossini, FP Steele, VE Boone, CW Kelloff, GJ AF Risio, M Lipkin, M Newmark, H Yang, K Rossini, FP Steele, VE Boone, CW Kelloff, GJ TI Apoptosis, cell replication, and Western-style diet-induced tumorigenesis in mouse colon SO CANCER RESEARCH LA English DT Article ID CANCER; HYPERPROLIFERATION; CARCINOGENESIS; PROLIFERATION; HISTOGENESIS; HYPERPLASIA; MICE AB In this study, feeding Western-style diets (WDs) to mice for a duration of two years, without any chemical carcinogen led to the development of gross colonic lesions that were histologically classified as dysplastic crypts and focal hyperplasias with or without atypical nuclei. To better understand early biological events contributing to the development of colonic neoplasia, grossly normal colonic mucosa was investigated; mitotic and apoptotic colonic epithelial cells, atypical mitosis, and atypical nuclei mere studied. A significant and transient increase of mitotic activity in the basal and intermediate portions of the colonic crypts was seen in young mice after feeding them the WDs. This was accompanied by diffuse activation of apoptosis of the colonic epithelial cells. In the middle of the rodents' life span, after administration of both the WDs and control diet, the rodents developed a marked depletion of apoptotic epithelial cells in the mid-region of the colonic crypts; this mas followed by the expansion of an epithelial cell population containing atypical nuclei, and the emergence of the gross lesions noted above. With this sequence of events, prolonged feeding of WDs to mice produced wingle-crypt dysplastic lesions and focal hyperplasias indicative of tumorigenesis. C1 ROCKEFELLER UNIV, STRANG CANC RES LAB, NEW YORK, NY 10021 USA. OSPED SAN GIOVANNI VECCHIO, CTR RIC NEOPLASIE APPARATO DIGERENTE L NOVELLO MI, I-10123 TURIN, ITALY. MEM SLOAN KETTERING CANC CTR, NEW YORK, NY 10021 USA. NCI, DIV CANC PREVENT & CONTROL,CANC RES PROGRAM, CHEMOPREVENT BRANCH,NIH, BETHESDA, MD 20852 USA. FU NCI NIH HHS [N01-CN-15363] NR 26 TC 86 Z9 87 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1996 VL 56 IS 21 BP 4910 EP 4916 PG 7 WC Oncology SC Oncology GA VP486 UT WOS:A1996VP48600017 PM 8895743 ER PT J AU vonBrevern, MC Hollstein, MC Cawley, HM DeBenedetti, VMG Bennett, WP Liang, L He, AG Zhu, SM Tursz, T Janin, N Trivers, GE AF vonBrevern, MC Hollstein, MC Cawley, HM DeBenedetti, VMG Bennett, WP Liang, L He, AG Zhu, SM Tursz, T Janin, N Trivers, GE TI Circulating anti-p53 antibodies in esophageal cancer patients are found predominantly in individuals with p53 core domain mutations in their tumors SO CANCER RESEARCH LA English DT Article ID SUPPRESSOR GENE; LUNG-CANCER; BREAST-CANCER; SERUM ANTIBODIES; IMMUNE-RESPONSE; PROTEIN; CARCINOMAS; EPITOPES; COMPLEX; CHINA AB Serum antibodies reacting with the tumor suppressor protein p53 have been detected previously in cancer patients with a variety of neoplasms, Two initial (although insufficient) prerequisites for a B-cell response to occur have been proposed: p53 protein accumulation in the tumor or a mutant p53 gene, or both. We have examined 65 esophageal cancer cases (42 from Guangzhou and Shenyang, People's Republic of China, and 23 from Paris, France) to obtain a prevalence estimate of anti-pb3 antibodies for this type of cancer and to define the relationship of p53 tumor status to B-cell immune response, Sera were analyzed in a triplicate assay (enzyme-linked immunoassay, immunoprecipitation, and immunoblot) for anti-p53 antibodies, Tumor DNA was screened for mutations in exons 5-8, and tumor tissue was examined by immunohistochemistry for abnormal p53 protein accumulation, p53 mutations were found in 36 (58%) of 62 cases analyzed. Sixteen patients (25%) had circulating antibodies to the tumor suppressor protein, All but two (88%) of the tumors from seropositive cases had a mutation in the DNA binding region of the p53 gene, and with one exception, these tumors also showed nuclear accumulation of the p53 protein, In contrast, tumor mutations were found in just 22 (46%) of the 48 individuals in whom we did not detect anti-p53 antibodies. Among the 22 seronegative cases for which we found no tumor mutations, 11 revealed pig protein accumulation by immunohistochemical analysis. Thus, circulating anti-p53 antibodies may be present in one-fourth of esophageal cancer patients, most of whom also would be expected to have a p53 gene mutation in their tumors, Patients without such mutations appear considerably less likely to mount a B-cell response to the p53 tumor suppressor protein than those that do (P < 0.01). C1 NCI,HUMAN CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. GERMAN CANC RES CTR,D-69120 HEIDELBERG,GERMANY. CHINA MED UNIV,SHENYANG,PEOPLES R CHINA. SUN YAT SEN UNIV MED SCI,GUANGZHOU,PEOPLES R CHINA. INST GUSTAVE ROUSSY,PARIS,FRANCE. NR 39 TC 63 Z9 63 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1996 VL 56 IS 21 BP 4917 EP 4921 PG 5 WC Oncology SC Oncology GA VP486 UT WOS:A1996VP48600018 PM 8895744 ER PT J AU Dunnick, JK Hailey, JR AF Dunnick, JK Hailey, JR TI Phenolphthalein exposure causes multiple carcinogenic effects in experimental model systems SO CANCER RESEARCH LA English DT Article ID FREE-RADICAL FORMATION; ANIMAL CARCINOGENICITY; THYMIC LYMPHOMA; GENTIAN-VIOLET; BRCA1 GENE; MICE; INDUCTION; TOXICITY; LEUKEMIA; ESTROGEN AB Phenolphthalein (a triphenylmethane derivative) has been commonly used as a laxative for most of the twentieth century, but little is known about its long-term carcinogenic potential in experimental studies. In our studies, phenolphthalein administered continuously in the feed for 2 ears to F344 rats at doses of 0, 12,500, 25,000, and 50,000 ppm and to C57BL/ 6 x CB3 F-1 (hereafter called B6C3F(1)) mice at doses of 0, 3,000, 6,000, and 12,000 ppm caused multiple carcinogenic effects. Treatment-related neoplasms occurred in the kidney and adrenal medulla in male rats, adrenal medulla in female rats, hematopoietic system in male and female mice (histiocytic sarcomas and malignant lymphomas), and ovary of female mice. Phenolphthalein has been shown to have estrogenic and clastogenic properties. Previous studies of other estrogenic chemicals (e.g., zearalenone) in the F344 rat and B6C3F(1) mouse have not shown the same spectrum of carcinogenic activity as that found with phenolphthalein, suggesting that phenolphthalein: estrogenic activity alone is not responsible for the spectrum of turners observed. It is more likely that the multiple biological properties of phenolphthalein, including its ability to form free radicals, its clastogenic activity, and its estrogenic activity, contributed to the carcinogenic effects observed. These studies show that phenolphthalein is a multisite/multispecies carcinogen. One of the sites for neoplasm that is of particular concern is the ovary, and epidemiology studies are under way to identify any potential effects of phenolphthalein exposure at this site in humans. RP Dunnick, JK (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 35 TC 62 Z9 64 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1996 VL 56 IS 21 BP 4922 EP 4926 PG 5 WC Oncology SC Oncology GA VP486 UT WOS:A1996VP48600019 PM 8895745 ER PT J AU Darwiche, N Scita, G Jones, C Rutberg, S Greenwald, E Tennenbaum, T Collins, SJ De Luca, LM Yuspa, SH AF Darwiche, N Scita, G Jones, C Rutberg, S Greenwald, E Tennenbaum, T Collins, SJ De Luca, LM Yuspa, SH TI Loss of retinoic acid receptors in mouse skin and skin tumors is associated with activation of the ras(Ha) oncogene and high risk for premalignant progression SO CANCER RESEARCH LA English DT Article ID ORNITHINE DECARBOXYLASE ACTIVITY; KERATINOCYTE DIFFERENTIATION; MALIGNANT PROGRESSION; EPIDERMAL-CELLS; RAS GENE; TERMINAL DIFFERENTIATION; CHEMICAL CARCINOGENESIS; MURINE KERATINOCYTES; NEGATIVE REGULATION; BENIGN-TUMORS AB Retinoic acid receptor transcripts (RAR alpha and RAR gamma) are decreased in benign mouse epidermal tumors relative to normal skin and are almost absent in carcinomas, In this report, the expression of RAR alpha and RAR gamma proteins was analyzed by immunoblotting in benign skin tumors induced by two different promotion protocols designed to yield tumors at low; or high risk for malignant conversion, RAR alpha mas slightly reduced in papillomas promoted with 12-O-tetradecanoylphorbol-13-acetate (low risk) and markedly decreased or absent in papillomas promoted by mezerein (high risk). However, mezerein also caused substantial reduction of RAR alpha in nontumorous skin, RAR gamma was not detected in tumors from either protocol and was greatly reduced in skin treated by either promoter. Both RAR alpha and RAR gamma proteins were decreased in keratinocytes overexpressing an oncogenic v-ras(H alpha) gene, and RAR alpha was underexpressed in a benign keratinocyte cell line carrying a mutated c-ras(H alpha) gene, Introduction of a recombinant RAR alpha expression vector into benign keratinocyte tumor cells reduced the S-phase population and inhibited [(3H)]thymidine incorporation in response to retinoic acid, Furthermore, transactivation of B-RARE-tk-LUC by retinoic acid was markedly decreased in keratinocytes transduced with the v-ras(H alpha) oncogene (v-ras(H alpha)-keratinocytes). Blocking protein kinase C function in v-ras(H alpha)-keratinocytes with bryostatin restored RAR alpha protein to near normal levels, reflecting the involvement of protein kinase C in RAR alpha regulation. Both RAR alpha and RAR gamma are downregulated in cultured keratinocytes by 12-O-tetradecanoylphorbol-13-acetate, further implicating PKC in the regulation of retinoid receptors, Our data suggest that modulation of RARs could contribute to the neoplastic phenotype in mouse skin carcinogenesis and map be involved in the differential promoting activity of mezerein and 12-O-tetradecanoylphorbol-13-acetate, particularly for selecting tumors at high risk for malignant conversion. C1 NCI, DIV BASIC SCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, NIH, BETHESDA, MD 20892 USA. FRED HUTCHINSON CANC RES CTR, DIV MOL MED, SEATTLE, WA 98104 USA. RI Scita, GIORGIO/J-9670-2012; OI Darwiche, Nadine/0000-0002-1862-5426; Scita, Giorgio/0000-0001-7984-1889 NR 61 TC 37 Z9 38 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1996 VL 56 IS 21 BP 4942 EP 4949 PG 8 WC Oncology SC Oncology GA VP486 UT WOS:A1996VP48600022 PM 8895748 ER PT J AU Simoneau, AR Spruck, CH GonzalezZulueta, M Gonzalgo, ML Chan, MF Tsai, YC Dean, M Steven, K Horn, T Jones, PA AF Simoneau, AR Spruck, CH GonzalezZulueta, M Gonzalgo, ML Chan, MF Tsai, YC Dean, M Steven, K Horn, T Jones, PA TI Evidence for two tumor suppressor loci associated with proximal chromosome 9p to q and distal chromosome 9q in bladder cancer and the initial screening for GAS1 and PTC mutations SO CANCER RESEARCH LA English DT Article ID TRANSITIONAL-CELL CARCINOMA; POLYMERASE CHAIN-REACTION; ARREST-SPECIFIC GENE; ALLELIC LOSSES; HOMOZYGOUS DELETIONS; POINT MUTATIONS; OVARIAN-CANCER; P16 GENE; POLYMORPHISMS; ALLELOTYPE AB The most common genetic alteration identified to date in bladder cancer is loss of heterozygosity (LOH) of chromosome 9, suggesting the presence of possible tumor suppressor genes on this chromosome. We attempted to map the location of these genes by analyzing 69 primary transitional cell carcinomas of the bladder with a panel of microsatellite markers for LOH on chromosome 9. Monosomy 9 (defined by LOH of all informative markers analyzed on 9p and 9q) was detected in 26 of 69 (38%) tumors, and 22 of 69 (32%) tumors showed subchromosomal deletions. Twelve tumors (17%) demonstrated partial LOH of chromosome 9 and indicated two distinct regions of LOH. Eight tumors showed distal allelic loss of 9q with a minimal region of common deletion flanked proximally by marker GSN on 9q33. Six tumors showed proximal allelic loss of 9p and 9q with a minimal area of common deletion flanked by markers D9S970 on 9p12 and D9S283 on 9q21. Two tumors showed loss of both the distal region of 9q and the proximal region of 9p and 9q, which were separated by a possible 6-44 cM of retained genetic material. The proximal minimal area of common deletion excluded 9q22.3-q31 to where two putative tumor suppressor genes, the nevoid basal cell carcinoma syndrome and multiple self-healing squamous epithelioma (ESS1) genes, have been mapped. The growth arrest-specific gene (GAS1), a candidate tumor suppressor gene, was included within the proximal minimal region. We evaluated the GAS1 gene for its potential role in bladder cancer using single-strand conformational polymorphism to screen for mutations in GAS1 in 10 bladder cancer cell lines and 14 primary bladder tumors. A polymorphism at codon 88 was noted in one primary bladder tumor, but no other abnormalities were found, suggesting that another potential tumor suppressor gene important to bladder cancer resides in these minimally deleted regions. Because the nevoid basal cell carcinoma syndrome gene has long been speculated to be a putative tumor suppressor gene in bladder cancer and this gene has recently been characterized as the human homologue of the Drosophila patched gene (PTC), 20 primary bladder tumors with chromosome 9q LOH were screened for mutations in PTC using single-strand conformational polymorphism and heteroduplex analysis. No alterations were found in any of the samples analyzed. Furthermore, 4 of 37 noninvasive papillary (T-a) tumors demonstrated loss of all 9q markers with retention of 9p, whereas no T-a tumor shelved loss of 9p with retention of all 9q markers, suggesting that LOH of 9q is the earlier event in bladder tumorigenesis. In summary, our results indicate two tumor suppressor loci associated with proximal chromosome 9p to q and distal chromosome 9q that may be important in bladder cancer, GAS1 and PTC do not seem to be frequently mutated in bladder cancer. C1 UNIV SO CALIF,KENNETH NORRIS JR COMPREHENS CANC CTR,SCH MED,UROL CANC RES LAB,LOS ANGELES,CA 90033. NCI,HUMAN GENET SECT,VIRAL CARCINOGENESIS LAB,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. UNIV COPENHAGEN,HERLEV HOSP,DK-2730 HERLEV,DENMARK. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU NCI NIH HHS [R35 CA49758] NR 50 TC 98 Z9 98 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1996 VL 56 IS 21 BP 5039 EP 5043 PG 5 WC Oncology SC Oncology GA VP486 UT WOS:A1996VP48600035 PM 8895761 ER PT J AU Steller, MA Zou, ZQ Schiller, JT Baserga, R AF Steller, MA Zou, ZQ Schiller, JT Baserga, R TI Transformation by human papillomavirus 16 E6 and E7: Role of the insulin-like growth factor 1 receptor SO CANCER RESEARCH LA English DT Article ID FACTOR-I RECEPTOR; MOUSE EMBRYO FIBROBLASTS; WILD-TYPE P53; INDUCED APOPTOSIS; IGF-1 RECEPTOR; BOVINE PAPILLOMAVIRUS; CELL-CYCLE; PROTEIN; GENE; OVEREXPRESSION AB Human papillomavirus-16 E6 and E7 inactivate the tumor suppressors p53 and pRB, respectively, and cooperate during malignant transformation, but the downstream molecular events remain incompletely understood, Using fibroblast cell lines derived from mice with a homozygous disruption of the insulin-like growth factor-1 receptor (IGF-1R) gene (R-cells) and their wild-type (WT) littermates, we have stably transfected plasmids encoding E6 and E7 proteins and examined their transforming potential in these cells, Consistent with previous studies using NIH3T3 cells, pooled cultures of E7-transfected WT cells readily formed colonies after suspension in soft agar, In contrast, R- cells were not transformed by E7, E6 had little transforming activity in WT (WT/E6) or R- (R-/E6) cells, However, transfection of R- cells with E6 plus E7 resulted in extensive colony formation, Because IGF-1R and E6 appear to be functionally equivalent in this transformation assay and both have been implicated in antiapoptotic responses, we investigated the apoptotic responses of the cells after exposure to the potent protein kinase C inhibitor, staurosporine. Compared to WT cells, R- cells were relatively resistant to staurosporine-induced apoptosis, but susceptibility to staurosporine was decreased in both WT/E6 and R-/E6 cells relative to WT and R- cells transfected with mock vector, respectively, In fibroblast cells from p53 gene knockout mice, transfection with E6 also conferred relative resistance to staurosporine-induced apoptosis, Our data suggest that transformation by E7 requires the participation of the IGF-1R and that E6 may assist E7 in transforming R- cells by functionally substituting for the IGP-1R, Because IGF-1R activated by its ligands (IGF-1 and IGF-2) protects cells from apoptosis, the role of the IGF-1R and E6 in transformation by E7 is probably related to the recruitment of survival pathways, In addition, because E6 suppressed apoptosis in p53 knockout cells, our data also suggest that E6 may participate in a p53-independent process that protects cells from apoptosis. C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,PHILADELPHIA,PA 19107. RP Steller, MA (reprint author), NCI,GYNECOL ONCOL SECT,SURG BRANCH,BLDG 10,ROOM 2B-42,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 43 TC 54 Z9 54 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1996 VL 56 IS 21 BP 5087 EP 5091 PG 5 WC Oncology SC Oncology GA VP486 UT WOS:A1996VP48600042 PM 8895768 ER PT J AU Shou, MG Krausz, KW Gonzalez, FJ Gelboin, HV AF Shou, MG Krausz, KW Gonzalez, FJ Gelboin, HV TI Metabolic activation of the potent carcinogen dibenzo[a,l]pyrene by human recombinant cytochromes P450, lung and liver microsomes SO CARCINOGENESIS LA English DT Article ID TUMOR-INITIATING ACTIVITY; RAT MAMMARY-GLAND; MOUSE SKIN; DIOL-EPOXIDES; FJORD-REGION; 11,12-DIHYDRODIOL 13,14-EPOXIDE; PULMONARY CARCINOMAS; VACCINIA VIRUS; NEWBORN MICE; EXPRESSION AB The metabolic activation of dibenzo[a,l]pyrene (DB[a,l]P), recently considered the most potent carcinogen among all polycyclic aromatic hydrocarbons, to the 11,12-dihydrodiol, a precursor of the ultimate carcinogens, the 11,12-diol-13,14-epoxides, was investigated using eleven human recombinant cytochrome P450s, as well as human lung and liver microsomes, Of all human P450s, 1A1 was the most active in the metabolism of DB[a,l]P (310 pmol/min, mmol P450) and had 5-23-fold higher catalytic activity than other P450s examined, The order of activity in the formation of the 11,12-dihydrodiol was as follows: 1A1 (116 pmol/min, nmol P450) > 2C9 (29) > 1A2 (22) > 2B6 (18) > 3A4 (16) > others (less than or equal to 5), The K-m of 1A1 for DB[a,l]P and V-max for the formation of 11,12-dihydrodiol were 3.9 mu M and 0.13/min, respectively, Liver microsomes from 14 individuals were shown to metabolize DB[a,l]P and the rates for production of 11,12-dihydrodiol ranged from 4 to 71 pmol/min, nmol P450, Lung microsomes from six organ donors formed the 11,12-dihydrodiol at a rate from 0.1 to 1.3 pmol/min, mg of microsomal protein, These findings describe the potential of individual P450s present in liver and lung to contribute to the metabolic activation and the carcinogenicity of DB[a,l]P. RP Shou, MG (reprint author), NCI,MOL CARCINOGENESIS LAB,NIH,BLDG 37,ROOM 3E24,BETHESDA,MD 20892, USA. NR 35 TC 56 Z9 59 U1 0 U2 2 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 NOV PY 1996 VL 17 IS 11 BP 2429 EP 2433 DI 10.1093/carcin/17.11.2429 PG 5 WC Oncology SC Oncology GA VW458 UT WOS:A1996VW45800022 PM 8968059 ER PT J AU Tamano, S Ward, JM Diwan, BA Keefer, LK Weghorst, CM Calvert, RJ Henneman, JR Ramljak, D Rice, JM AF Tamano, S Ward, JM Diwan, BA Keefer, LK Weghorst, CM Calvert, RJ Henneman, JR Ramljak, D Rice, JM TI Histogenesis and the role of p53 and K-ras mutations in hepatocarcinogenesis by glyceryl trinitrate (nitroglycerin) in male F344 rats SO CARCINOGENESIS LA English DT Article ID NITRIC-OXIDE SYNTHASE; IN-VITRO; NITRATE TOLERANCE; ORGANIC NITRATES; LIVER-TUMORS; H-RAS; MECHANISMS; APOPTOSIS; ACTIVATION; CARCINOGENICITY AB Glyceryl trinitrate (GTN) was previously reported to induce hepatocellular carcinoma (HCC) in rats after prolonged feeding, The present experiments were undertaken to evaluate the histogenesis and molecular biology of these tumors and the possible role of nitric oxide (NO), a GTN metabolite, in their development, Male F344 rats received a single i.g. intubation of GTN (1.2 g/kg) at 6 weeks of age and/or a diet containing 1% GTN from 8 weeks of age until necropsy, i.e. for up to 78 weeks, Some animals were subjected to 2/3 partial hepatectomy (PH) at 9 weeks of age, Five sequential sacrifices (14, 32, 52, 78 and 84 weeks of age) were performed, No liver tumors developed in control rats or in rats that received GTN only by a single i.g. intubation, even when intubation was followed by PH, Preneoplastic foci, mainly of clear cell and mixed cell type (identified as positive for glutathione S-transferase placental form) were found from 14 weeks of age in rats receiving GTN in the diet, Focal eosinophilic areas (atypical foci) composed of atypical hepatocytes that often extended into the veins were observed beginning at 52 weeks of age, Some mixed hepatocholangiocellular adenomas and carcinomas arose in eosinophilic lesions, HCCs were seen beginning at 78 weeks of age, but only in rats receiving dietary GTN, Incidence of HCC in the latter animals was 50-75%, Most HCCs were well differentiated, The carcinogenic effect of GTN given in the diet was not affected by prior intubation of a large single dose followed by PH, No p53 mutations were found in 18 tumors but K-ras point mutations, all within codon 12, were found in 8/18 tumors, mostly those with cholangiocellular elements, These were first or second position G-->T transversions or second position G-->A transitions, While these mutation types have also been commonly seen in bacteria after NO-related DNA damage, the fact that tumors arose only on prolonged feeding of this potently bioactive agent at massive doses seems consistent with a more complex mechanism involving multiple (i.e. genetic and/or epigenetic) factors in carcinogenesis by GTN. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,OFF LAB ANIM SCI,VET & TUMOR PATHOL SECT,FREDERICK,MD 21702. SAIC FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD 21702. US FDA,CTR FOOD SAFETY & APPL NUTR,OFF SPECIAL NUTR,CLIN RES & REVIEW STAFF,LAUREL,MD 20708. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NCI NIH HHS [N01-CO-56000] NR 50 TC 17 Z9 17 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 NOV PY 1996 VL 17 IS 11 BP 2477 EP 2486 DI 10.1093/carcin/17.11.2477 PG 10 WC Oncology SC Oncology GA VW458 UT WOS:A1996VW45800029 PM 8968066 ER PT J AU Graziewicz, M Wink, DA Laval, F AF Graziewicz, M Wink, DA Laval, F TI Nitric oxide inhibits DNA ligase activity: Potential mechanisms for NO-mediated DNA damage SO CARCINOGENESIS LA English DT Article ID WOODCHUCK HEPATITIS-VIRUS; PEROXYNITRITE CAUSES; REPAIR PROTEIN; MARMOTA-MONAX; IN-VITRO; CELLS; AGENTS; GENE; MUTATIONS; RELEASE AB Nitric oxide-induced modifications of DNA occur either by directly altering DNA chemically through reactive nitrogen oxide species (RNOS) or indirectly by inhibiting various repair processes, DNA ligases are enzymes which rejoin single-strand breaks and are critical for DNA integrity during processes such as gene transcription and repair, The eukaryotic and T4 DNA ligases are active in the presence of ATP and act in two steps: the formation of protein-AMP intermediates, then the ligation of DNA breaks, When T4 DNA ligase was exposed to the NO generator DEA/NO (Et(2)N[NO(NO)]Na), a concentration- and time-dependent inhibition of these two steps, adenylylation of the protein and ligation of the substrate, was observed, This inhibition was abated by the presence of cysteine, suggesting that RNOS, rather than NO, mediated the inhibition of the ligase activity, As mammalian and T4 DNA ligases act by the same mechanism, the inhibition of DNA ligase may explain the increase in single-strand breaks reported for cells exposed to NO and provides a mechanism to increase DNA lesions without direct chemical modification of DNA by NO or RNOS. C1 U347 INSERM,F-94276 LE KREMLIN BICETR,FRANCE. NCI,RADIAT BIOL BRANCH,NIH,BETHESDA,MD 20893. NR 42 TC 87 Z9 90 U1 0 U2 2 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 NOV PY 1996 VL 17 IS 11 BP 2501 EP 2505 DI 10.1093/carcin/17.11.2501 PG 5 WC Oncology SC Oncology GA VW458 UT WOS:A1996VW45800032 PM 8968069 ER PT J AU McCormick, DL Johnson, WD Rao, KVN BowmanGram, T Steele, VE Lubet, RA Kelloff, GJ AF McCormick, DL Johnson, WD Rao, KVN BowmanGram, T Steele, VE Lubet, RA Kelloff, GJ TI Comparative activity of N-(4-hydroxyphenyl)-all-trans-retinamide and alpha-difluoromethylornithine as inhibitors of lymphoma induction in PIM transgenic mice SO CARCINOGENESIS LA English DT Article ID URINARY-BLADDER CARCINOGENESIS; MAMMARY CARCINOGENESIS; RETINYL ACETATE; N-(4-HYDROXYPHENYL)RETINAMIDE; CANCER; RAT; CHEMOPREVENTION; PREDISPOSITION; LEUKEMIA; THERAPY AB The activities of the retinoid, N-(4-hydroxyphenyl)-all-trans-retinamide (4-HPR) and the polyamine synthesis inhibitor, alpha-difluoromethylornithine (DFMO), as inhibitors of lymphoma induction in PIM transgenic mice were evaluated, Lymphoma was induced in male PIM mice by a single intraperitoneal injection of 50 mg N-ethyl-N-nitrosourea (ENU) per kg body weight, Continuous dietary administration of 4-HPR (391, 196 or 98 mg/kg diet) or DFMO (1000, 500 or 250 mg/kg diet) was initiated immediately after ENU administration, and was continued until the end of the study at 35 weeks, At 20 weeks: post-ENU, the high dose of 4-HPR reduced both lymphoma incidence and associated mortality, However, the protection conferred by 4-HPR represented a delay rather than an inhibition of neoplastic development, since both lymphoma incidence and mortality at study termination were similar in dietary controls and all groups treated with 4-HPR. DFMO had no effect on lymphoma incidence, latency or mortality at any point in the study, These results suggest that 4-HPR or other retinoids may be effective in the prevention of lymphoma induction, whereas inhibition of polyamine biosynthesis does not appear to present a useful mechanistic target for the chemoprevention of lymphoid neoplasia, The PIM transgenic mouse provides a useful in vivo model for the rapid evaluation of chemopreventive agents. C1 NCI,CHEMOPREVENT INVEST STUDIES BRANCH,BETHESDA,MD 20892. RP McCormick, DL (reprint author), IIT,RES INST,DEPT LIFE SCI,CHICAGO,IL 60616, USA. FU NCI NIH HHS [N01-CN-85097-13] NR 19 TC 21 Z9 21 U1 1 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 NOV PY 1996 VL 17 IS 11 BP 2513 EP 2517 DI 10.1093/carcin/17.11.2513 PG 5 WC Oncology SC Oncology GA VW458 UT WOS:A1996VW45800034 PM 8968071 ER PT J AU Sakata, H Takayama, H Sharp, R Rubin, JS Merlino, G LaRochelle, WJ AF Sakata, H Takayama, H Sharp, R Rubin, JS Merlino, G LaRochelle, WJ TI Hepatocyte growth factor scatter factor overexpression induces growth, abnormal development, and tumor formation in transgenic mouse livers SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID MET PROTOONCOGENE PRODUCT; C-MET; EPITHELIAL-CELLS; FACTOR-ALPHA; FACTOR-RECEPTOR; CARCINOMA-CELLS; GENE-EXPRESSION; MESSENGER-RNA; STEM-CELL; MICE AB To investigate the in vivo role of hepatocyte growth factor/scatter factor (HGF/SF) in liver function, we generated transgenic mice using a mouse HGF/SF cDNA under the control of the mouse metallothionein gene promoter and 5'/3' flanking sequences. In adult HGF/SF transgenic mice, liver weight as a percentage of total body weight was at least twice that of wildtype mice. Comparison of transgenic and control liver morphology revealed dramatic heterogeneity in the size and appearance of hepatocytes as a distinctive feature of HGF/SF overexpression. Transgenic livers exhibited a significant increase in the number of small hepatocytes with a 2N DNA content, accounting for the observed increase in liver mass. The DNA labeling index of hepatocytes increased 11-fold at 4 weeks of age, when liver enlargement first became apparent, and was still elevated about 5-fold in adult HGF/SF transgenic mice. Moreover, hepatocytes isolated by perfusion of transgenic livers doubled every 2 days in culture, whereas little or no growth was observed with isolated control hepatocytes. The mechanistic basis of hepatocyte proliferation was elucidated as the chronic activation of the c-met proto-oncogene product. Met and substrates such as phosphatidylinositol 3-kinase. Src homology and collagen-like, pp60(c-src), focal adhesion kinase p125(FAK), and paxillin were associated with tyrosine-phosphorylated complexes in a hepatocyte cell line established from the transgenic liver. This proliferative stimulus triggered the formation of hepatocellular adenomas and/or carcinomas in most transgenic mice greater than or equal to 1.5 years of age. Finally, the rate of transgenic mouse liver regeneration was increased 3-fold over control livers following partial hepatectomy. C1 NCI,CELLULAR & MOL BIOL LAB,BETHESDA,MD 20892. NCI,MOL BIOL LAB,BETHESDA,MD 20892. NR 54 TC 134 Z9 136 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 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD NOV PY 1996 VL 7 IS 11 BP 1513 EP 1523 PG 11 WC Cell Biology SC Cell Biology GA VT231 UT WOS:A1996VT23100010 PM 8930401 ER PT J AU Athanasiou, M Clausen, PA Mavrothalassitis, GJ Zhang, XK Watson, DK Blair, DG AF Athanasiou, M Clausen, PA Mavrothalassitis, GJ Zhang, XK Watson, DK Blair, DG TI Increased expression of the ETS-related transcription factor FLI-1/ERGB correlates with and can induce the megakaryocytic phenotype SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID EWINGS-SARCOMA TRANSLOCATION; MURINE LEUKEMIA-VIRUS; CELL-LINE; GENE-EXPRESSION; ACUTE ERYTHROLEUKEMIAS; HEMATOPOIETIC-CELLS; ALPHA-GENE; EWS GENE; FAMILY; DIFFERENTIATION AB The human leukemia cell line K562 can be induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) to differentiate along the megakaryocytic pathway, generating morphological changes and increased expression of lineage-specific surface markers. We report that TPA-treated K562 cells also express higher levels of FLI-1/ERGB, a member of the ETS family of transcription factors. Furthermore, introduction of a retroviral construct expressing human FLI-1/ERGB into K562 cells induces changes similar to those seen following TPA treatment, including increased adherence to the surface of the culture vessel and altered size and morphology. Infected cells exhibit higher levels of the megakaryocyte marker CD41a and, to a lesser extent, CD49b. These markers, as well as virally encoded FLI-1/ERGB-specific RNA and protein, are expressed at the highest levels in the attached cell population, while the growth rate of adherent cells is reduced, and the fraction of cells in G(0)-G(1) is increased. FLI-1/ERGB virus-infected cells also exhibit increased expression of hemoglobin, a marker of erythroid differentiation. Our results suggest FLI-1/ERGB plays a role in controlling differentiation and gene expression along the megakaryocyte/platelet pathway, and further implicate ETS-related genes in the control of multiple developmentally regulated hematopoietic genes. C1 NCI,DBS,LAB DIRECTOR,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,FREDERICK,MD 21702. MED UNIV S CAROLINA,CTR MOL & STRUCT BIOL,CHARLESTON,SC 29425. NR 68 TC 71 Z9 74 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 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD NOV PY 1996 VL 7 IS 11 BP 1525 EP 1534 PG 10 WC Cell Biology SC Cell Biology GA VT231 UT WOS:A1996VT23100011 PM 8930402 ER PT J AU Turley, JM Falk, LA Ruscetti, FW Kasper, JJ Francomano, T Fu, T Bang, OS BirchenallRoberts, MC AF Turley, JM Falk, LA Ruscetti, FW Kasper, JJ Francomano, T Fu, T Bang, OS BirchenallRoberts, MC TI Transforming growth factor beta 1 functions in monocytic differentiation of hematopoietic cells through autocrine and paracrine mechanisms SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID TUMOR NECROSIS FACTOR; TRANS-RETINOIC ACID; TGF-BETA; PROMYELOCYTIC LEUKEMIA; RECEPTOR EXPRESSION; FACTOR-BETA-1; LINES; HL-60; PROLIFERATION; INDUCTION AB This study examined the role of transforming growth factor beta 1 (TGF-beta 1) in monocytic differentiation of hematopoietic cells, TGF-beta 1 and retinoic acid (RA) inhibited HL-60 cell growth in a dose-dependent fashion. Treatment of HL-60 cells with a combination of TGF-beta 1 and a 50% optimal dose of RA (RA + TGF-beta 1) resulted in increased growth suppression compared to the individual treatments, Morphological studies revealed that TGF-beta 1 induced promonocytic differentiation (68%), RA induced granulocytic differentiation (98%), and RA + TGF-beta 1 induced monocytic (54%) and granulocytic (46%) differentiation of HL-60 cells. Induction of the monocyte-specific marker, nonspecific esterase, was markedly increased by TGF-beta 1 and RA + TGF-beta 1 treatment but not by RA treatment. Both TGF-beta 1 treatment and RA treatment increased TGF-beta ligand and TGF-beta receptor protein and mRNA levels. To determine whether RA mediated HL-60 cell growth inhibition and differentiation through the autocrine expression of TGF-beta 1, experiments using TGF-beta 1 antisense oligonucleotides or TGF-beta 1-neutralizing antibodies were conducted, TGF-beta 1 antisense oligonucleotides and neutralizing antibodies partially blocked RA-induced inhibition of proliferation, and TGF-beta 1 antisense oligonucleotides reversed RA-induced granulocytic maturation, demonstrating that RA signals autocrine expression of TGF-beta 1 and TGF-beta receptors. The effect of TGF-beta 1 on normal hematopoiesis was also studied using primary human fetal liver cells, TGF-beta 1 alone and in the presence of interleukin 3 promoted macrophage differentiation of primitive fetal liver cells. Cell surface expression of the monocyte/macrophage-specific marker c-fms was increased 3.1-fold following TGF-beta 1 treatment. In addition, TGF-beta 1-treated cells displayed a 51% increase in phagocytosis as compared to interleukin 3-treated control cells. These studies define a role for TGF-beta 1 in the autocrine and paracrine regulation of monocyte/macrophage differentiation. C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. SCI APPLICAT INT CORP,DIV BASIC SCI,LAB LEUKOCYTE BIOL,FREDERICK,MD. SCI APPLICAT INT CORP,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD. NR 32 TC 44 Z9 44 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 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD NOV PY 1996 VL 7 IS 11 BP 1535 EP 1544 PG 10 WC Cell Biology SC Cell Biology GA VT231 UT WOS:A1996VT23100012 PM 8930403 ER PT J AU Mertz, PM Corcoran, ML McCluskey, KM Zhang, YH Wong, HL Lotze, MT DeWitt, DL Wahl, SM Wahl, LM AF Mertz, PM Corcoran, ML McCluskey, KM Zhang, YH Wong, HL Lotze, MT DeWitt, DL Wahl, SM Wahl, LM TI Suppression of prostaglandin H synthase-2 induction in human monocytes by in vitro or in vivo administration of interleukin 4 SO CELLULAR IMMUNOLOGY LA English DT Article ID MATRIX METALLOPROTEINASE PRODUCTION; HUMAN ALVEOLAR MACROPHAGES; GENE-EXPRESSION; RHEUMATOID SYNOVITIS; MESSENGER-RNA; IL-4; CYCLOOXYGENASE; INHIBITION; COLLAGENASE; BIOSYNTHESIS AB IL-4 is a potent modulator of monocyte function, Our previous studies demonstrated that the suppression of monocyte matrix metalloproteinase production by IL-4 is a result of its inhibition of PGE(2) synthesis, which was attributed to an effect on prostaglandin synthase. Here we report on the in vitro and in vivo effects of IL-4 on monocyte prostaglandin H synthase-2 (PGHS-2) and its regulation by second messengers. Stimulation of monocytes with either LPS or Con A resulted in the induction of PGHS-2 which was significantly inhibited by IL-4, Inhibition of PGHS-2 mRNA and protein was detected at 0.05 to 0.1 ng/ml of IL-4 with substantial suppression at 10 to 20 ng/ml. If added later than 2 hr after LPS, IL-4 failed to suppress PGHS-2, indicating that IL-4 acted early in the signaling cascade, Moreover, the ability of exogenously added PGE(2) or Bt(2)cAMP to restore PGHS-2 production in IL-4-treated monocytes further suggested early disruption of the pathway, The early event inhibited by IL-4 did not involve suppression of phospholipase activity, because LPS-induced arachidonic acid release was relatively unaffected by IL-4. Unlike PGHS-2, PGHS-1, the constitutively expressed PGHS, was not modulated by IL-4. Thus, IL-4 appears to selectively block PGHS-2 synthesis, thereby blocking subsequent steps in the pathway leading to the production of matrix metalloproteinases, In an extension of these findings, we examined peripheral blood monocytes from cancer patients undergoing IL-4 therapy, In these cells the induction of PGHS-2 expression by LPS was significantly reduced compared to that of monocytes obtained prior to IL-4 therapy, Although perhaps not relevant as an antitumor mechanism, these findings have important implications in defining the potent anti-inflammatory activities of IL-4 in vitro and in vivo. (C) 1996 Academic Press, Inc. C1 NIDR,IMMUNOL LAB,NIH,CELLULAR IMMUNOL SECT,BETHESDA,MD 20892. NCI,SURG BRANCH,NIH,BETHESDA,MD 20892. MICHIGAN STATE UNIV,DEPT BIOCHEM,E LANSING,MI 48824. NR 44 TC 12 Z9 12 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 NOV 1 PY 1996 VL 173 IS 2 BP 252 EP 260 DI 10.1006/cimm.1996.0275 PG 9 WC Cell Biology; Immunology SC Cell Biology; Immunology GA VV113 UT WOS:A1996VV11300012 PM 8912884 ER PT J AU Magae, J Matsubara, H Aotsuka, N Kurasawa, K Shearer, GM AF Magae, J Matsubara, H Aotsuka, N Kurasawa, K Shearer, GM TI Interleukin-2 does not overcome suppression of graft rejection by cyclosporin A: Effect of cyclosporin A on T cell properties in vivo SO CELLULAR IMMUNOLOGY LA English DT Article ID SIGNAL TRANSDUCTION; TYROSINE KINASE; PRODIGIOSIN 25-C; MINIATURE SWINE; LYMPHOCYTES-T; CLASS-I; RECEPTOR; ALLOGRAFTS; INDUCTION; TRANSCRIPTION AB The most evident immunosuppressive effect of cyclosporin A (CsA) on T cells is suppression of interleukin-2 (IL-2) production through the suppression of type-2B serine/threonine-specific phosphatase, calcineurin, To test whether suppression of IL-2 production is a major mechanism of CsA-mediated suppression of allograft rejection, we treated allogeneic skin-grafted mice with CsA and IL-2, and observed that IL-2 did not override the suppressive effect of CsA. Specific cytotoxic T lymphocyte (CTL) activity and natural killer (NK) activity of the spleens were increased by treatment with IL-2, and CsA significantly suppressed the killing activity, We also found that CsA-treatment decreased the expression of Ick kinase of T cells and the production of IL-2 in response to concanavalin A (ConA), with minimum effect on IL-4 production, These results suggest that T cell dysfunctions other than decreased production of IL-2 are essential for suppressive effect of CsA on skin allograft rejection. (C) 1996 Academic Press, Inc. C1 NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NR 31 TC 4 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD NOV 1 PY 1996 VL 173 IS 2 BP 276 EP 281 DI 10.1006/cimm.1996.0278 PG 6 WC Cell Biology; Immunology SC Cell Biology; Immunology GA VV113 UT WOS:A1996VV11300015 PM 8912887 ER PT J AU Lenfant, C AF Lenfant, C TI Conference on socioeconomic status and cardiovascular health and disease SO CIRCULATION LA English DT News Item RP Lenfant, C (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA. NR 1 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 NOV 1 PY 1996 VL 94 IS 9 BP 2041 EP 2044 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN754 UT WOS:A1996VN75400001 PM 8901646 ER PT J AU Lynn, F Reed, GF Meade, BD AF Lynn, F Reed, GF Meade, BD TI Collaborative study for the evaluation of enzyme-linked immunosorbent assays used to measure human antibodies to Bordetella pertussis antigens SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID INFECTION; SEROLOGY; VACCINE; TRIAL AB Acellular pertussis vaccines are being evaluated in multiple clinical studies, and human immunogenicity data will likely be pivotal in the appraisal of vaccine responses between populations and the responses to different vaccine combinations. Antibody response to pertussis antigens is also used in the diagnosis of pertussis. An international study was designed to assess the comparability of data generated in different laboratories by enzyme-linked immunosorbent assays (ELISAs). Thirty-three participating laboratories were asked to quantitate specific antibody to pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), or fimbrial proteins (FIM) in 21 samples. Samples were to be assayed in triplicate in five independent assays by each ELISA routinely performed in the laboratory to assess intra-assay, interassay, and population variability. The mean sample values were used to compare quantitative results among the laboratories. Thirteen of the 32 laboratories which submitted evaluable data for an assay to measure antibodies to PT, 12 of 30 laboratories with assays for FHA, 10 of 17 laboratories with assays for PRN, and 6 of 13 laboratories with assays for FIM maintained a coefficient of variation below 20% for 75% of the samples tested. Assays that measure antibodies to FIM appear to be less precise than the other assays. Precision varied among laboratories that used similar methods. The relative values of intra- and interassay variabilities were not consistent for a given assay within a laboratory, indicating that the sources of these variability components may be unrelated. Precision and agreement appeared less reliable for samples with low antibody levels. Ranking and regression analyses suggest that some laboratories generated comparable quantitative results, although direct comparison or combination of results from different laboratories remains difficult to support. Calibration to the U.S. Reference Pertussis Antisera appears to have been successful at standardizing the results in some laboratories, Statistical analyses are affected by assay precision and are not necessarily reliable sole predictors of biologically relevant differences in quantitative results. If results from different laboratories must be compared, appropriate studies of precision and quantitative agreement should be conducted to support the specific comparisons. C1 NIAID,BIOMETRY BRANCH,BETHESDA,MD 20892. NIAID,DIV MICROBIOL & INFECT DIS,BETHESDA,MD 20892. RP Lynn, F (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,LAB PERTUSSIS,HFM-490,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 22 TC 48 Z9 49 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD NOV PY 1996 VL 3 IS 6 BP 689 EP 700 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VQ351 UT WOS:A1996VQ35100012 PM 8914760 ER PT J AU Shirasaka, T Kojima, E Mitsuya, H AF Shirasaka, T Kojima, E Mitsuya, H TI Stability of HIV-1 RNA in blood samples from patients with HIV-1 infection as determined by a quantitative polymerase chain reaction-based assay SO CLINICAL AND DIAGNOSTIC VIROLOGY LA English DT Letter ID IMMUNODEFICIENCY-VIRUS TYPE-1; PLASMA; VIREMIA; VIRIONS C1 NCI,EXPT RETROVIROL SECT,MED BRANCH,DIV CLIN SCI,BETHESDA,MD 20892. NR 15 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-0197 J9 CLIN DIAGN VIROL JI Clin. Diagn. Virol. PD NOV PY 1996 VL 7 IS 2 BP 121 EP 124 DI 10.1016/S0928-0197(96)00256-5 PG 4 WC Virology SC Virology GA WH084 UT WOS:A1996WH08400007 PM 9137868 ER PT J AU Meredith, RF Khazaeli, MB Plott, WE Grizzle, WE Liu, TP Schlom, J Russell, CD Wheeler, RH LoBuglio, AF AF Meredith, RF Khazaeli, MB Plott, WE Grizzle, WE Liu, TP Schlom, J Russell, CD Wheeler, RH LoBuglio, AF TI Phase II study of dual I-131-labeled monoclonal antibody therapy with interferon in patients with metastatic colorectal cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-ASSOCIATED GLYCOPROTEIN-72; CARCINOEMBRYONIC ANTIGEN; RADIOIMMUNOTHERAPY TRIAL; CARCINOMA PATIENTS; GAMMA-INTERFERON; IMMUNE-RESPONSE; CELLS; EXPRESSION; PHARMACOKINETICS; DOSIMETRY AB The combination of COL-1 (anti-CEA) and CC49 (anti-TAG-72) has shown an increase in binding and distribution in colon cancer by immunoperoxidase staining compared to either antibody alone, To overcome tumor heterogeneity and allow delivery of higher radiation dose, I-131-labeled COL-1 and CC49 at a total dose of 75 mCi/m(2) (2775 MBq/m(2)) were simultaneously administered to 14 patients with metastatic colon cancer, alpha-IFN (3 x 10(6) IU) was given s.c. on days -5 to +3 to increase carcinoembryonic antigen and TAG-72 antigen expression, Most patients had mild symptoms during IFN therapy, including mild neutropenia, fever, and malaise, which rapidly subsided after IFN cessation, No acute allergic reactions occurred with radioimmunotherapy; two patients experienced transient, delayed grade 2 arthralgias, Transient neutropenia and/or thrombocytopenia, which was maximal at 4-6 weeks, were consistent side effects without adverse events, All patients had tumor localization, and 13 of 14 patients achieved 4+ (highest grade) localization readings to at least one known site of disease, No objective responses occurred; 4 patients were stable and 10 progressed, Tumor dose estimates varied from 393 to 1327 cGy, including liver and extrahepatic sites, Combining two complementary antibodies and IFN administration appeared to increase localization intensity and radiation doses at tumor sites as compared to historical controls, The amount of radiation delivered to tumor sites was still below that required to cause tumor regressions in metastatic colorectal cancer. C1 UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT PATHOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT NUCL MED,BIRMINGHAM,AL 35294. NCI,BETHESDA,MD 20892. RP Meredith, RF (reprint author), UNIV ALABAMA,DEPT RADIAT ONCOL,LB WALLACE TUMOR INST,1824 6TH AVE S,BIRMINGHAM,AL 35294, USA. FU NCI NIH HHS [CM 87215]; NCRR NIH HHS [MO1-RR-00032] NR 40 TC 48 Z9 49 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 NOV PY 1996 VL 2 IS 11 BP 1811 EP 1818 PG 8 WC Oncology SC Oncology GA VQ901 UT WOS:A1996VQ90100001 PM 9816134 ER PT J AU Moore, TA Reynolds, JC Kenney, RT Johnston, W Nutman, TB AF Moore, TA Reynolds, JC Kenney, RT Johnston, W Nutman, TB TI Diethylcarbamazine-induced reversal of early lymphatic dysfunction in a patient with bancroftian filariasis: Assessment with use of lymphoscintigraphy SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID EXPERIMENTAL-INFECTION; ONCHOCERCIASIS; HUMANS AB Exposure of expatriates to the infective larvae of Wuchereria bancrofti can result in the early development of signs of lymphatic obstruction, The findings on the clinical presentation of expatriates are distinct from the chronic pathological findings seen among the native population and are similar to the findings in experimentally infected persons. We report the case of a Peace Corps volunteer who developed acute lymphatic dysfunction within 3 months of arriving in an area that was endemic for filariasis, The diagnosis was established clinically and by demonstrating the presence of antibodies to recombinant proteins specific for patients with lymphatic filariasis, Lymphatic flow was markedly abnormal when assessed with use of Tc-99m-lymphoscintigraphy. Treatment with diethylcarbamazine reversed both the physical and lymphoscintigraphic abnormalities. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT NUCL MED,BETHESDA,MD 20892. PEACE CORPS,MED UNIT,LIBREVILLE,GABON. RP Moore, TA (reprint author), NIAID,NIH,PARASIT DIS LAB,BLDG 4,ROOM 126,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 21 TC 11 Z9 11 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV PY 1996 VL 23 IS 5 BP 1007 EP 1011 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VQ906 UT WOS:A1996VQ90600011 PM 8922794 ER PT J AU Vogel, N Kirisits, M Michael, E Bach, H Hostetter, M Boyer, K Simpson, R Holfels, E Hopkins, J Mack, D Mets, MB Swisher, CN Patel, D Roizen, N Stein, L Stein, M Withers, S Mui, E Egwuagu, C Remington, J Dorfman, R McLeod, R AF Vogel, N Kirisits, M Michael, E Bach, H Hostetter, M Boyer, K Simpson, R Holfels, E Hopkins, J Mack, D Mets, MB Swisher, CN Patel, D Roizen, N Stein, L Stein, M Withers, S Mui, E Egwuagu, C Remington, J Dorfman, R McLeod, R TI Congenital toxoplasmosis transmitted from an immunologically competent mother infected before conception SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID POLYMERASE-CHAIN-REACTION; ACUTE ACQUIRED TOXOPLASMOSIS; LINKED IMMUNOSORBENT-ASSAY; PRENATAL-DIAGNOSIS; GONDII; IDENTIFICATION; LYMPHADENITIS; PREGNANCIES; ANTIBODIES; ANTIGEN AB Congenital transmission of Toxoplasma gondii from a mother who was apparently immunologically competent and who had toxoplasmic lymphadenitis 2 months before conception is described, Since no T. gondii-specific serological data were available for this mother from the time her lymph node biopsy specimen was obtained, the specimen was studied by polymerase chain reaction (PCR) to determine whether the T, gondii B1 gene was present. The predictive diagnostic value of histologic findings previously considered to be classic signs of T, gondii lymphadenitis also was studied, This was done by correlation of serological tests diagnostic of acute acquired T. gondii infection and presence of characteristic findings in biopsy specimens from persons without known immunocompromise. Both PCR and review of the characteristic features of her lymph node biopsy specimen confirmed the diagnosis of preconceptual infection in the mother, We also discuss two other cases in which apparently immunologically competent mothers with preconceptually acquired infection transmitted this parasite to their fetuses. C1 UNIV ILLINOIS,DEPT MED,MICHAEL REESE HOSP & MED CTR,CHICAGO,IL 60616. UNIV CHICAGO,RUSH MED SCH,CHICAGO,IL 60637. IIT,NORTHWESTERN CHILDRENS HOSP,CHICAGO,IL 60616. NORTHWESTERN UNIV,CHICAGO,IL 60611. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. METHODIST HOSP,MINNEAPOLIS,MN 55455. STANFORD UNIV,STANFORD,CA 94305. NEI,NIH,BETHESDA,MD 20892. FU NIAID NIH HHS [AI 108749, AI 27530] NR 26 TC 47 Z9 53 U1 0 U2 1 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 NOV PY 1996 VL 23 IS 5 BP 1055 EP 1060 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VQ906 UT WOS:A1996VQ90600019 PM 8922802 ER PT J AU Pastorek, JG Cotch, MF Martin, DH Eschenbach, DA Yaffe, SJ Catz, CS Rhoads, GG McNellis, D Nugent, RP Klebanoff, MA Berendes, HW Hoffman, H Edelman, R Kaslow, RA Blackwelder, WC Reed, GF Williams, S Greenberg, EM Regan, JA Geromanos, KL Hillier, S Krohn, MA Lee, M Carey, JC Rettig, PJ Meier, A Gibbs, RS Lipscomb, KA Wenthold, L Summers, P Poole, WK Rao, AV Hastings, B AF Pastorek, JG Cotch, MF Martin, DH Eschenbach, DA Yaffe, SJ Catz, CS Rhoads, GG McNellis, D Nugent, RP Klebanoff, MA Berendes, HW Hoffman, H Edelman, R Kaslow, RA Blackwelder, WC Reed, GF Williams, S Greenberg, EM Regan, JA Geromanos, KL Hillier, S Krohn, MA Lee, M Carey, JC Rettig, PJ Meier, A Gibbs, RS Lipscomb, KA Wenthold, L Summers, P Poole, WK Rao, AV Hastings, B TI Clinical and microbiological correlates of vaginal trichomoniasis during pregnancy SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID BACTERIAL VAGINOSIS; PREMATURE RUPTURE; ADOLESCENTS; MEMBRANES; DISEASE; WOMEN AB Colonization with Trichomonas vaginalis is a possible cause of poor pregnancy outcome, To facilitate the diagnosis of this condition during pregnancy, we conducted a prospective, multicenter study of 13,816 gravid women who were between the 23rd and 26th week of gestation. Findings significantly associated with T. vaginalis colonization included a yellow, green, or bloody discharge from the vagina or cervix; abnormal odor after KOH was added to a vaginal specimen; a vaginal pH of >5.0; and cervical friability, The amount of vaginal discharge and abnormal consistency of the discharge were also associated with T. vaginalis colonization, These findings (except for cervical bleeding and odor after the addition of KOH to a vaginal specimen, which may be influenced by the presence of other flora) are consistent with those reported elsewhere. The clinical usefulness of these features is minimal, and it is more significant that other microorganisms are markers for trichomoniasis; therefore, controlling for other flora is important in the investigation of T. vaginalis colonization. C1 LOUISIANA STATE UNIV, MED CTR, DEPT MED, NEW ORLEANS, LA 70112 USA. NIAID, BETHESDA, MD 20892 USA. UNIV WASHINGTON, DEPT OBSTET & GYNECOL, SEATTLE, WA USA. RP Pastorek, JG (reprint author), LOUISIANA STATE UNIV, MED CTR, DEPT OBSTET & GYNECOL, 1542 TULANE AVE, NEW ORLEANS, LA 70112 USA. OI Cotch, Mary Frances/0000-0002-2046-4350 FU Intramural NIH HHS [Z99 EY999999]; NICHD NIH HHS [HD3-2834, HD-3-2832, HD-3-2833] NR 21 TC 20 Z9 22 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV PY 1996 VL 23 IS 5 BP 1075 EP 1080 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VQ906 UT WOS:A1996VQ90600023 PM 8922806 ER PT J AU Sran, PK Kansupada, K Whitcup, SM AF Sran, PK Kansupada, K Whitcup, SM TI Mycobacterium chelonae infection mimicking cutaneous vasculitis: Case report SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CLARITHROMYCIN; SULFONAMIDES C1 NEI,NIH,BETHESDA,MD 20892. NR 9 TC 6 Z9 6 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV PY 1996 VL 23 IS 5 BP 1189 EP 1191 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VQ906 UT WOS:A1996VQ90600052 PM 8922834 ER PT J AU Klein, SL AF Klein, SL TI Background, recommendations and overview SO COMPUTERIZED MEDICAL IMAGING AND GRAPHICS LA English DT Editorial Material RP Klein, SL (reprint author), NICHHD,DEV BIOL GENET & TERATOL BRANCH,NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-6111 J9 COMPUT MED IMAG GRAP JI Comput. Med. Imaging Graph. PD NOV-DEC PY 1996 VL 20 IS 6 BP 407 EP 409 DI 10.1016/S0895-6111(96)00037-7 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WE969 UT WOS:A1996WE96900001 PM 9007207 ER PT J AU Jezzard, P Turner, R AF Jezzard, P Turner, R TI Magnetic resonance imaging methods for study of human brain function and their application at high magnetic field SO COMPUTERIZED MEDICAL IMAGING AND GRAPHICS LA English DT Article; Proceedings Paper CT Workshop on Computer-assisted Imaging of Embryonic and Fetal Development CY JUN 23-24, 1994 CL N, BETHESDA, MD SP NICHHD HO N DE magnetic resonance imaging; MRI; functional brain imaging; fast imaging ID CEREBRAL BLOOD-FLOW; HUMAN VISUAL-CORTEX; TRANSVERSE RELAXATION; SENSORY STIMULATION; CONTRAST; OXYGENATION; NMR; TIME; MRI; EPI AB Magnetic resonance imaging (MRI) sequences are finding a new application in the study of human brain function by monitoring localized changes in signal intensity which accompany neuronal activity. These sequences can be sensitized to changes in cerebral blood volume, cerebral blood flow, and blood oxygenation, all of which reflect aspects of neuronal activity in the brain. Many of these experiments benefit from being implemented at a higher magnetic field strength than conventional MRI. An overview of these techniques is presented, and examples of their use are given. RP Jezzard, P (reprint author), NIH,CARDIAC ENERGET LAB,BLDG 10 ROOM B1D161,BETHESDA,MD 20892, USA. RI Turner, Robert/C-1820-2008; OI Jezzard, Peter/0000-0001-7912-2251 NR 34 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-6111 J9 COMPUT MED IMAG GRAP JI Comput. Med. Imaging Graph. PD NOV-DEC PY 1996 VL 20 IS 6 BP 467 EP 481 DI 10.1016/S0895-6111(96)00044-4 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WE969 UT WOS:A1996WE96900008 PM 9007214 ER PT J AU Jensen, PS AF Jensen, PS TI Adolescent psychiatry: Developmental and clinical studies, vol 20 - Marohn,RC, Feinstein,SC SO CONTEMPORARY PSYCHOLOGY LA English DT Book Review RP Jensen, PS (reprint author), NIMH,CHILD & ADOLESCENT DISORDERS RES BRANCH,ROCKVILLE,MD 20857, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0010-7549 J9 CONTEMP PSYCHOL JI Comtemp. Psychol. PD NOV PY 1996 VL 41 IS 11 BP 1133 EP 1134 PG 2 WC Psychology, Multidisciplinary SC Psychology GA VQ908 UT WOS:A1996VQ90800034 ER PT J AU Peculis, BA Mount, SM AF Peculis, BA Mount, SM TI Ribosomal RNA: Small nucleolar RNAs make their mark SO CURRENT BIOLOGY LA English DT Article AB Small nucleolar RNAs direct the location of certain methylations in ribosomal RNA by direct base pairing; although evolutionarily conserved, the physiological significance of these modifications remains unclear. C1 UNIV MARYLAND,DEPT ZOOL,COLLEGE PK,MD 20742. RP Peculis, BA (reprint author), NIH,GENET & BIOCHEM BRANCH,NIDDK,BETHESDA,MD 20892, USA. NR 10 TC 21 Z9 21 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD NOV 1 PY 1996 VL 6 IS 11 BP 1413 EP 1415 DI 10.1016/S0960-9822(96)00745-2 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VT119 UT WOS:A1996VT11900022 PM 8939586 ER PT J AU DiBernardo, BE Giampapa, VC Vogel, J AF DiBernardo, BE Giampapa, VC Vogel, J TI Standardized hair photography SO DERMATOLOGIC SURGERY LA English DT Article AB BACKGROUND. Photographs currently published or used clinically in hair restorative surgery vary greatly in positioning, lighting, posing, and technique. OBJECTIVE. The purpose of this work is to aid in standardizing these variables and to review the necessary equipment and techniques required to achieve these goals. METHODS. Nine standardized views are shown. Also addressed is hairline depiction taking into account variable hair styles. CONCLUSION. Standardization is achieved with consistent reproduction of patient photographs in hair restoration. (C) 1996 by the American Society for Dermatologic Surgery, Inc. C1 NIAMSD,MONTCLAIR,NJ. UNIV MED & DENT NEW JERSEY,DIV PLAST & RECONSTRUCT SURG,NEWARK,NJ 07103. NR 1 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD NOV PY 1996 VL 22 IS 11 BP 945 EP 952 PG 8 WC Dermatology; Surgery SC Dermatology; Surgery GA WL636 UT WOS:A1996WL63600007 PM 9063510 ER PT J AU Passer, BJ Chen, CLH Miller, NW Cooper, MD AF Passer, BJ Chen, CLH Miller, NW Cooper, MD TI Identification of a T lineage antigen in the catfish SO DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY LA English DT Article DE Ictalurus punctatus; catfish; T cells; T cell antigen; monoclonal antibody ID CHANNEL CATFISH; CELL-LINES; LYMPHOCYTE HETEROGENEITY; MONOCLONAL-ANTIBODIES; ICTALURUS-PUNCTATUS; MOLECULAR-CLONING; BRACHYDANIO-RERIO; COMPLEX; GENES; LEUKOCYTES AB A murine monoclonal antibody produced against catfish thymocytes and immunoglobulin-negative lymphocytes in the blood identified a catfish T cell antigen designated CfT1, The CfT1 antigen was found to be expressed on thymocytes, a subpopulation of the lymphoid cells in blood and other lympho-hemopoietic tissues, and a T cell line, but was not expressed by erythrocytes, thrombocytes, myeloid cells, B cells or macrophage cell lines. Stimulation of blood mononuclear cells with the T cell mitogen, concanavalin A, resulted in an increased frequency of CfT1(+) cells, Conversely, lipopolysaccharide stimulation increased the number of IgM(+) B cells and decreased the frequency of CfT1(+) cells. The CfT1 antigen was defined as a single chain protein of M(r) 35 000 lacking N- and O-linked sugars. The CfT1 molecule thus provides a T lineage-specific marker in this bony fish representative. Copyright (C) 1996 Elsevier Science Ltd. C1 UNIV ALABAMA,HOWARD HUGHES MED INST,DIV DEV & CLIN IMMUNOL,WALLACE TUMOR INST 378,DEPT MED,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT MICROBIOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT PEDIAT,BIRMINGHAM,AL 35294. UNIV MISSISSIPPI,MED CTR,DEPT MICROBIOL,JACKSON,MS 39216. NIAID,MOL STRUCT LAB,NIH,ROCKVILLE,MD 20852. NR 37 TC 26 Z9 26 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0145-305X J9 DEV COMP IMMUNOL JI Dev. Comp. Immunol. PD NOV-DEC PY 1996 VL 20 IS 6 BP 441 EP 450 DI 10.1016/S0145-305X(96)00033-X PG 10 WC Immunology; Zoology SC Immunology; Zoology GA WF714 UT WOS:A1996WF71400007 PM 9040986 ER PT J AU Winning, RS Scales, JB Sargent, TD AF Winning, RS Scales, JB Sargent, TD TI Disruption of cell adhesion in Xenopus embryos by Pagliaccio, an Eph-class receptor tyrosine kinase SO DEVELOPMENTAL BIOLOGY LA English DT Article ID PROTEIN-SYNTHESIS; CDNA CLONING; FAMILY; CADHERIN; LIGANDS; GENE; EXPRESSION; GUIDANCE; BINDING; LAEVIS AB Pagliaccio (Pag) is a receptor tyrosine kinase of the Eph family that is expressed in Xenopus embryos in a diverse set of localized tissues. Fag is the Xenopus homolog of Hek-8 (human), Sek-1 (mouse), cek8 (chicken), and RTK-1 (zebrafish). We have investigated the function of this protein by injecting RNA encoding an epidermal growth factor receptor-Fag chimera into early Xenopus embryos. Activation of the chimeric receptor results in a kinase-dependent loss of cell-cell adhesion. This dissociation can be reversed by co-injection of RNA encoding C-cadherin, suggesting that one or more cadherins could be the functional targets for Fag activity. (C) 1996 Academic Press, Inc. C1 NICHHD,MOL GENET LAB,NIH,BETHESDA,MD 20892. RP Winning, RS (reprint author), EASTERN MICHIGAN UNIV,DEPT BIOL,YPSILANTI,MI 48197, USA. NR 39 TC 72 Z9 72 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 NOV 1 PY 1996 VL 179 IS 2 BP 309 EP 319 DI 10.1006/dbio.1996.0262 PG 11 WC Developmental Biology SC Developmental Biology GA VT146 UT WOS:A1996VT14600001 PM 8903347 ER PT J AU Terasaki, M Jaffe, LA Hunnicutt, GR Hammer, JA AF Terasaki, M Jaffe, LA Hunnicutt, GR Hammer, JA TI Structural change of the endoplasmic reticulum during fertilization: Evidence for loss of membrane continuity using the green fluorescent protein SO DEVELOPMENTAL BIOLOGY LA English DT Article ID SEA-URCHIN EGGS; LUMINAL ER PROTEINS; FREE CALCIUM WAVE; OOPLASMIC SEGREGATION; SPATIAL-DISTRIBUTION; MEIOTIC MATURATION; STARFISH OOCYTES; ASCIDIAN EGG; CA2+ WAVE; ACTIVATION AB Green fluorescent protein (GFP) was targeted to the lumen of the endoplasmic reticulum (ER) of starfish eggs by injecting mRNA coding for a chimeric protein containing a signal sequence and the KDEL ER retention sequence. By confocal microscopy, the GFP chimeric protein was localized in intracellular cisternae (membrane sheets) and the nuclear envelope, showing that it had been successfully targeted to the ER. The labeling pattern closely resembled that produced by the fluorescent dicarbocyanine DiI, which has been used previously to label the ER (Jaffe and Terasaki, Dev. Biol. 164, 579-587, 1994). Eggs expressing the GFP chimera were used to examine whether there is a loss of ER continuity at fertilization, The time required for recovery of fluorescence after photobleaching for both the GFP chimera and DiI was much longer in eggs at 1 min postfertilization than in unfertilized eggs or in 20 min-postfertilized eggs. This result provides strong evidence for a transient loss of continuity of the ER associated with Ca release at fertilization. (C) 1996 Academic Press, Inc. C1 UNIV CONNECTICUT, CTR HLTH, DEPT PHYSIOL, FARMINGTON, CT 06032 USA. NHLBI, CELL BIOL LAB, NIH, BETHESDA, MD 20892 USA. RP MARINE BIOL LAB, WOODS HOLE, MA 02543 USA. OI Hammer, John/0000-0002-2496-5179 FU NICHD NIH HHS [HD-14939] NR 46 TC 80 Z9 82 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 EI 1095-564X J9 DEV BIOL JI Dev. Biol. PD NOV 1 PY 1996 VL 179 IS 2 BP 320 EP 328 DI 10.1006/dbio.1996.0263 PG 9 WC Developmental Biology SC Developmental Biology GA VT146 UT WOS:A1996VT14600002 PM 8903348 ER PT J AU Matten, WT Copeland, TD Ahn, NG VandeWoude, GF AF Matten, WT Copeland, TD Ahn, NG VandeWoude, GF TI Positive feedback between MAP kinase and Mos during Xenopus oocyte maturation SO DEVELOPMENTAL BIOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; MEIOTIC MATURATION; ONCOGENE PRODUCT; TYROSINE PHOSPHORYLATION; CYTOSTATIC FACTOR; FROG OOCYTES; CELL-CYCLE; IN-VITRO; EGGS; IDENTIFICATION AB Mos is a serine-threonine protein kinase and a key regulator of meiosis. One function of Xenopus Mos is to activate mitogen-activated protein kinase (MAPK) through direct phosphorylation and activation of MAPK kinase (MAPKK). All three members of this signal cascade can individually induce hormone-independent reentry of oocytes into meiosis I. However, their inducing efficiency is reduced in the absence of protein synthesis. Here we show that de novo Mos synthesis is required for induction of meiosis I by active MAPKK or Mos-MAPK coinjection. In addition, MAPK efficiently phosphorylates Mos at Ser-3 in vitro. These results suggest that a positive feedback loop exists between MAPK and Mos during oocyte maturation. De novo synthesis of Mos, and other proteins, is required for progression from meiosis I to the metaphase arrest at meiosis II; therefore, one function of MAPK during normal Xenopus oocyte maturation might be to stimulate the synthesis or accumulation of Mos that is required for the completion of meiosis. (C) 1996 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. UNIV COLORADO,HOWARD HUGHES MED INST,DEPT CHEM & BIOCHEM,BOULDER,CO 80309. FU NIGMS NIH HHS [GM 4852] NR 49 TC 85 Z9 86 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD NOV 1 PY 1996 VL 179 IS 2 BP 485 EP 492 DI 10.1006/dbio.1996.0277 PG 8 WC Developmental Biology SC Developmental Biology GA VT146 UT WOS:A1996VT14600016 PM 8903362 ER PT J AU Tsang, M Lijam, N Yang, YS Beier, DR WynshawBoris, A Sussman, DJ AF Tsang, M Lijam, N Yang, YS Beier, DR WynshawBoris, A Sussman, DJ TI Isolation and characterization of mouse Dishevelled-3 SO DEVELOPMENTAL DYNAMICS LA English DT Article DE dishevelled; mouse development; gene expression ID GLYCOGEN-SYNTHASE KINASE-3; ZESTE-WHITE-3 KINASE; INSITU HYBRIDIZATION; INT-1 PROTOONCOGENE; XENOPUS EMBRYOS; WINGLESS SIGNAL; WNT GENES; DROSOPHILA; POLARITY; EXPRESSION AB The Drosophila dishevelled (dsh) segment polarity gene is required to establish cell fates specified by wingless/Wnt signal transduction during development. We have previously reported the cloning and characterization of a mouse homolog of dishevelled, Dvl1. Utilizing RT-PCR with degenerate primers, we isolated another member of the mouse Dishevelled (Dvl) gene family, Dvl3, The Dvl3 gene maps to mouse chromosome 16. The predicted amino acid sequence shares 64 and 62% identity to Dvl1 and Dvl2, respectively. The region of highest conservation between all three Dvl coding regions, at 97% identity, is noted at the PDZ domain (also termed the DHR domain or GLGF moth), a motif of 60 amino acids present in all dishevelled encoded proteins and first described in the Drosophila discs large (dlg) tumor suppressor gene. In adult mice, Dvl3 expression is widespread with highest levels exhibited in brain, ovary, and heart. In embryos, Dvl3 is expressed in every tissue between 7.5 and 9.5 days postcoitum, and by 10.5 days postcoitum highest expression was seen in the dorsal root ganglia, somites, limb buds, branchial arches, heart, gut, and throughout the developing central nervous system. (C) 1996 Wiley-Liss, Inc. C1 UNIV MARYLAND,DIV HUMAN GENET,BALTIMORE,MD 21201. NIH,NATL CTR HUMAN GENOME RES,LGDR,BETHESDA,MD 20892. BRIGHAM & WOMENS HOSP,DIV GENET,BOSTON,MA 02115. RI TSANG, Michael/E-2758-2013; Tsang, Michael/I-9305-2014 OI TSANG, Michael/0000-0001-6384-2422; Tsang, Michael/0000-0001-7123-0063 FU NCI NIH HHS [R55 CA63929]; NHGRI NIH HHS [R01 HG 00951]; NICHD NIH HHS [R01 HD29102] NR 52 TC 74 Z9 81 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 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD NOV PY 1996 VL 207 IS 3 BP 253 EP 262 DI 10.1002/(SICI)1097-0177(199611)207:3<253::AID-AJA2>3.0.CO;2-G PG 10 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA VR125 UT WOS:A1996VR12500002 PM 8922524 ER PT J AU Suomi, SJ Novak, MA Well, A AF Suomi, SJ Novak, MA Well, A TI Aging in rhesus monkeys: Different windows on behavioral continuity and change SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID MACACA-MULATTA; ENRICHMENT; OLD AB Rhesus monkeys were observed longitudinally from 6 to 20 years of age, the period encompassing early to late adulthood in this species. Repeated-measures analyses of the monkeys' behavioral repertoire revealed 3 quite different pictures of the aging process. First, there were significant systematic changes in the levels of many categories of behavior with increasing age, although the direction and timing of change varied from category to category. Second, for most categories, individual differences among the monkeys were highly stable from early to late adulthood. Finally, there was remarkable consistency within individual behavioral profiles across the entire study such that each monkey retained its distinctive behavioral features (personality) throughout its adult years. Thus, aging in rhesus monkeys is characterized by both continuity and change. C1 UNIV MASSACHUSETTS,DEPT PSYCHOL,AMHERST,MA 01003. UNIV MASSACHUSETTS,NEUROSCI & BEHAV PROGRAM,AMHERST,MA 01003. RP Suomi, SJ (reprint author), NICHHD,COMPARAT ETHOL LAB,BLDG 31,ROOM B2B15,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 32 TC 38 Z9 40 U1 1 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD NOV PY 1996 VL 32 IS 6 BP 1116 EP 1128 PG 13 WC Psychology, Developmental SC Psychology GA VT148 UT WOS:A1996VT14800015 ER PT J AU Karter, AJ MayerDavis, EJ Selby, JV DAgostino, RB Haffner, SM Sholinsky, P Bergman, R Saad, MF Hamman, RF AF Karter, AJ MayerDavis, EJ Selby, JV DAgostino, RB Haffner, SM Sholinsky, P Bergman, R Saad, MF Hamman, RF TI Insulin sensitivity and abdominal obesity in African-American, Hispanic, and non-Hispanic white men and women the insulin resistance and atherosclerosis study SO DIABETES LA English DT Article ID BODY-FAT DISTRIBUTION; ADIPOSE-TISSUE DISTRIBUTION; GLUCOSE-TOLERANCE TEST; CARDIOVASCULAR-DISEASE; DIABETES-MELLITUS; MEXICAN-AMERICANS; MINIMAL MODEL; PREMENOPAUSAL WOMEN; SERUM-LIPIDS; RISK-FACTORS AB Increased abdominal obesity has been related to lower insulin sensitivity (S-I), independent of overall obesity, but it has been suggested that this relationship may be weaker in non-whites. In the Insulin Resistance and Atherosclerosis Study (IRAS), S-I was estimated using a minimal model analysis of the frequently sampled intravenous glucose tolerance test in 1,625 men and women aged 40-69 years. Subjects included African-Americans, Hispanics, and non-Hispanic whites from Oakland and Los Angeles, CA, San Antonio, TX, and the San Luis Valley, CO. Minimum waist circumference was significantly (P = 0.0001) associated with S-I after adjusting for age, sex, height, BMI, glucose tolerance status, ethnicity, and clinic. This relationship was significantly (P = 0.0001) stronger in subjects with normal glucose tolerance (NGT) (beta = -0.030, P 0.0001) than in those with impaired glucose tolerance (IGT) (beta = -0.010, P = 0.02; NIDDM: beta = -0.013, P 0.0001). There were no significant ethnic differences in effect size across the spectrum of glucose tolerance. Waist circumference was also positively related to fasting insulin, an indirect measure of insulin sensitivity, in NGT (P = 0.0001), IGT (P = 0.0003), and NIDDM (P = 0.0002). The waist-fasting insulin relationship was significantly weaker in African-Americans, relative to non-Hispanic whites, in NGT and IGT (tests of statistical interaction: P = 0.04 and P = 0.02, respectively). In general, these patterns were similar in models specifying waist-to-hip ratio (WHR), rather than waist circumference, as the independent variable. While some ethnic variability exists, a negative relationship between abdominal obesity and insulin sensitivity was confirmed for all three ethnic groups across the spectrum of glucose tolerance. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. UNIV TEXAS,HLTH SCI CTR,DIV CLIN EPIDEMIOL,SAN ANTONIO,TX. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,NIH,BETHESDA,MD 20892. UNIV SO CALIF,DEPT MED,LOS ANGELES,CA. UNIV COLORADO,HLTH SCI CTR,DEPT PREVENT MED & BIOMETR,DENVER,CO 80262. RP Karter, AJ (reprint author), KAISER PERMANENTE,DIV RES,3505 BROADWAY,NO CALIF REG,OAKLAND,CA 94611, USA. RI Dagostino Jr, Ralph/C-4060-2017 OI Dagostino Jr, Ralph/0000-0002-3550-8395 FU NHLBI NIH HHS [HL-K03-P] NR 49 TC 140 Z9 142 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 1996 VL 45 IS 11 BP 1547 EP 1555 DI 10.2337/diabetes.45.11.1547 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VN855 UT WOS:A1996VN85500014 PM 8866560 ER PT J AU Ferris, FL Chew, EY Hoogwerf, BJ AF Ferris, FL Chew, EY Hoogwerf, BJ TI Serum lipids and diabetic retinopathy SO DIABETES CARE LA English DT Editorial Material C1 CLEVELAND CLIN FDN, CLEVELAND, OH 44195 USA. RP Ferris, FL (reprint author), NEI, NIH,BLDG 31,ROOM 6A52,31 CTR DR, MSC 2510, BETHESDA, MD 20892 USA. FU Intramural NIH HHS [Z99 EY999999] NR 11 TC 52 Z9 53 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD NOV PY 1996 VL 19 IS 11 BP 1291 EP 1293 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VN631 UT WOS:A1996VN63100024 PM 8908399 ER PT J AU Pettitt, DJ Narayan, KMV Hanson, RL Knowler, WC AF Pettitt, DJ Narayan, KMV Hanson, RL Knowler, WC TI Incidence of diabetes mellitus in women following impaired glucose tolerance in pregnancy is lower than following impaired glucose tolerance in the non-pregnant state SO DIABETOLOGIA LA English DT Article DE diabetes mellitus incidence; impaired glucose tolerance; pregnancy ID PIMA-INDIANS; PREVALENCE AB Impaired glucose tolerance (IGT), which is asymptomatic and requires a glucose tolerance test for detection, is a well-known risk factor for diabetes mellitus, Outside the research setting it is rarely identified in people who lack specific risk factors for diabetes except during pregnancy, at which time screening with an oral glucose challenge is a routine procedure. A 75-g oral glucose tolerance lest was performed during the latter part of pregnancy or during a routine epidemiology survey in 15-39-year-old Pima Indian women with no history of abnormal glucose tolerance. Those with IGT by World Health Organization criteria were included in this study. Diabetes incidence in women was compared between those whose IGT was first detected during pregnancy and those who were not pregnant when IGT was first recognized. Seventeen of 73 pregnant women and 114 of 244 non-pregnant women developed diabetes within 10 years. When controlled for plasma glucose concentration, age body mass index, parity and duration of follow-up, those who were not pregnant were at higher risk of developing diabetes than these who were pregnant (hazard rate ratio = 1.71, 95 % confidence interval = 1.01-2.91). Previous studies had reported that women with IGT during pregnancy are at higher risk of diabetes than women with normal glucose tolerance. This study suggests that: women with IGT during pregnancy are at lower risk than non-pregnant women with a similar plasma glucose concentration who, in the clinical setting, are likely to remain unrecognized. C1 NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,DIABET & ARTHRIT EPIDEMIOL SECT,PHOENIX,AZ. 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 27 TC 9 Z9 10 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD NOV PY 1996 VL 39 IS 11 BP 1334 EP 1337 DI 10.1007/s001250050579 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VQ310 UT WOS:A1996VQ31000015 PM 8933001 ER PT J AU Knowler, WC AF Knowler, WC TI Association of Trp64Arg mutation of the beta 3-adrenergic receptor gene with NIDDM SO DIABETOLOGIA LA English DT Letter ID BETA(3)-ADRENERGIC-RECEPTOR GENE; DIABETES-MELLITUS RP Knowler, WC (reprint author), NIDDK,1550 E INDIAN SCH RD,PHOENIX,AZ 85014, USA. NR 5 TC 3 Z9 4 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD NOV PY 1996 VL 39 IS 11 BP 1411 EP 1411 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VQ310 UT WOS:A1996VQ31000032 PM 8933017 ER PT J AU Chu, KU Ishizuka, J Battey, JF Uchida, T Beauchamp, RD Townsend, CM Thompson, JC AF Chu, KU Ishizuka, J Battey, JF Uchida, T Beauchamp, RD Townsend, CM Thompson, JC TI Mechanisms of bombesin on growth of gastrinoma (PT) in vivo SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE gastrinoma; bombesin; growth; gastrin ID ZOLLINGER-ELLISON SYNDROME; PEPTIDE ANTAGONIST RC-3095; HUMAN COLON CANCER; CELL LUNG-CANCER; SOMATOSTATIN ANALOG; TUMOR-GROWTH; NEUROMEDIN-B; RECEPTOR ANTAGONIST; STIMULATES GROWTH; ENDOCRINE TUMORS AB The growth of the human gastrinoma model (PT) in athymic nude mice is stimulated by bombesin (BBS), an amphibian peptide homologous to both human gastrin-releasing peptide (GRP) and neuromedin B (NMB). The mechanism is not known, and a potent and specific GRP-R antagonist BIM26226, which has low affinity for NMB-R, was used in vivo in athymic nude mice bearing gastrinoma subcutaneously. Both the BBS and BIM26226 stimulated the growth of PT, and the growth stimulation was even greater when given together. RT-PCR study of gastrinoma revealed the presence of both GRP-R and NMB-R mRNA, but much more abundant NMB-R mRNA. We conclude that BBS-stimulated growth of gastrinoma involves both GRP-R and NMB-R, and our findings suggest that GRP-R mediates negative and NMB-R produces positive growth effects on gastrinoma. C1 UNIV TEXAS,MED BRANCH,DEPT SURG,GALVESTON,TX 77555. UNIV TEXAS,MED BRANCH,DEPT BIOSTAT,GALVESTON,TX 77555. NIDOCD,NIH,DIV INTRAMURAL RES,BETHESDA,MD 20892. OI Beauchamp, Robert Daniel/0000-0002-8446-4114 FU NIDDK NIH HHS [2R01 DK 15241, P01 DK35608] NR 49 TC 6 Z9 6 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD NOV PY 1996 VL 41 IS 11 BP 2180 EP 2186 DI 10.1007/BF02071398 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VU837 UT WOS:A1996VU83700010 PM 8943970 ER PT J AU Edman, JC Hatton, TW Nam, M Turner, R Mei, Q Angus, CW Kovacs, JA AF Edman, JC Hatton, TW Nam, M Turner, R Mei, Q Angus, CW Kovacs, JA TI A single expression site with a conserved leader sequence regulates variation of expression of the Pneumocystis carinii family of major surface glycoprotein genes SO DNA AND CELL BIOLOGY LA English DT Article ID CULTURED LUNG-CELLS; ANTIGENIC VARIATION; IDENTIFICATION; DIVERSITY; PROTEIN; RNA; RAT; PURIFICATION; FIBRONECTIN; MECHANISM AB The major surface glycoprotein (MSG) of Pneumocystis carinii is encoded by a family of related but distinct genes distributed throughout the P. carinii genome, Previous reports of the genomic and mRNA MSG structure suggested that there was a highly conserved 5'-untranslated region and a highly variable translated region, In the current study, we demonstrate that there is a single expression site for MSG expression and that different MSG genes are located downstream of this expression site, Isolation of a genomic clone containing the putative 5'-untranslated region has demonstrated that there was a single base sequencing error in what was considered to be the untranslated region, The corrected sequence reveals an extended open reading frame encoding a constant amino-terminal leader domain, with a typical signal peptide, for the MSG protein family, Since this constant amino-terminal domain is encoded by a single copy genomic sequence, a recombination/gene conversion-mediated antigenic switching event is required to effect the known variability in expressed MSG sequences. Therefore, like some bacterial and protozoan pathogens, the opportunistic fungal pathogen P. carinii contains a constant genomic site dedicated to MSG expression and a switchable downstream region for the variable part of the MSG gene family. C1 NIH,CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT LAB MED,SAN FRANCISCO,CA 94143. FU NIAID NIH HHS [R01 AI27128] NR 43 TC 45 Z9 45 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD NOV PY 1996 VL 15 IS 11 BP 989 EP 999 DI 10.1089/dna.1996.15.989 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA VW075 UT WOS:A1996VW07500010 PM 8945640 ER PT J AU Boyer, JL Schachter, JB Sromek, SM Palmer, RK Jacobson, KA Nicholas, RA Harden, TK AF Boyer, JL Schachter, JB Sromek, SM Palmer, RK Jacobson, KA Nicholas, RA Harden, TK TI Avian and human homologues of the P2Y(1) receptor: Pharmacological, signaling, and molecular properties SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE P2Y; receptor; P2Y receptors; phospholipase C; P2 receptor antagonist ID TURKEY ERYTHROCYTE-MEMBRANES; PHOSPHOLIPASE-C; P2Y-PURINERGIC RECEPTOR; G-PROTEIN; ADENYLYL-CYCLASE; 2-THIOETHER DERIVATIVES; PURINERGIC RECEPTOR; GUANINE-NUCLEOTIDES; ATP RECEPTOR; IDENTIFICATION AB The P2Y receptor on turkey erythrocyte membranes was the first P2 receptor to be shown to activate phospholipase C (PLC) in a strictly guanine nucleotide-dependent manner and remains the only G protein-coupled P2 receptor for which G protein-coupling kinetics have been defined. This membrane receptor has provided a model system for detailed pharmacological analyses of a series of chain-extended 2-thioether derivatives of adenine nucleotides that exhibit remarkable selectivity and potency for P2Y receptors. This model system also has led recently to identification of a novel series of P2 receptor antagonists. The turkey erythrocyte receptor is the species homologue of the chick P2Y(1) receptor originally cloned by Webb and coworkers [Webb et al., 1993]. We also have cloned the human homologue of the P2Y(1) receptor, which exhibits identical pharmacological and second messenger signaling properties to that of the avian P2Y(1) receptor. (C) 1997 Wiley-Liss, Inc. C1 UNIV N CAROLINA,DEPT PHARMACOL,SCH MED,CHAPEL HILL,NC 27599. NIDDK,BIOORGAN CHEM LAB,MOL RECOGNIT SECT,NIH,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 34 TC 17 Z9 17 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 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD NOV-DEC PY 1996 VL 39 IS 3-4 BP 253 EP 261 DI 10.1002/(SICI)1098-2299(199611/12)39:3/4<253::AID-DDR4>3.0.CO;2-Q PG 9 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WW013 UT WOS:A1996WW01300004 ER PT J AU Jacobson, KA Suzuki, F AF Jacobson, KA Suzuki, F TI Recent developments in selective agonists and antagonists acting at purine and pyrimidine receptors SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE agonists; antagonists; adenosine; ATP; structure activity relationships; xanthines ID A(3) ADENOSINE RECEPTORS; HIGH-AFFINITY; 2-THIOETHER DERIVATIVES; ADENINE-NUCLEOTIDES; P-2 PURINOCEPTORS; MOLECULAR-CLONING; POTENT; PHARMACOLOGY; RADIOLIGAND; RESPONSES AB The SAR at adenosine (P-1) and ATP (P-2) receptors is reviewed, with emphasis on recently developed selective agonists and antagonists. These include partial (e.g., N-6-ethyl-8-cyclopentylaminoadenosine) and full A(1) agonists (e.g., NNC 21-0136, 2-chloro-N-6-[(R)(benzothiazolylthio-2-propyl]adenosine), A(2) antagonists (e.g., the non-xanthines: SCH58261, 5-amino-7-(phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine and ZM241385, 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3a][1,3,5]triazinyl-amino]ethyl)-phenol; and the 1-propargyl-8-styrylxanthines), and A(3) agonists (e.g., Cl-lB-MECA, 2-chloro-N-6-(3-iodobenzyl)-adenosine-5'-N-methyluron-amide). Novel adenosine receptor antagonists (e.g., BTH4, ethyl 3-benzylthio-4,5,6,7-tetrahydro-benzo[c]thiophen-4-one-1-carboxylate) have been discovered through screening libraries of natural products and heterocyclic derivatives. The first A(3) selective antagonists to be identified include derivatives of flavones (MRS 1067), 1,4-dihydropyridines (MRS 1097), triazolonaphthyridine (L-249313), and thiazolopyrimidine (L-268605). Potent P-2 receptor agonists are known. For example, 2-HexylthioAMP is a highly potent agonist at the yet uncloned P2Y receptor in C6 glioma cells. Suramin is a weak and non-selective P-2 blocker, while a truncated derivative, NF023, appears to be selective for P2X receptors. More selective P-2 antagonists are under development, with the cloning of these receptors. [S-35]ATP-gamma-S has been used as a radioligand for the direct labeling of several subtypes of cloned P2X receptors (P2X(1)-P2X(4)). (C) 1997 Wiley-Liss, Inc. C1 KYOWA HAKKO KOGYO CO LTD,DRUG EXPLORATORY RES,SHIZUOKA,JAPAN. RP Jacobson, KA (reprint author), NIDDK,BIOORGAN CHEM LAB,MOL RECOGNIT SECT,NIH,BETHESDA,MD 20892, USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 70 TC 60 Z9 60 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 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD NOV-DEC PY 1996 VL 39 IS 3-4 BP 289 EP 300 DI 10.1002/(SICI)1098-2299(199611/12)39:3/4<289::AID-DDR8>3.0.CO;2-N PG 12 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WW013 UT WOS:A1996WW01300008 ER PT J AU Roy, SK Moschel, RC Dolan, ME AF Roy, SK Moschel, RC Dolan, ME TI Pharmacokinetics and metabolism in rats of 2,4-diamino-6-benzyloxy-5-nitrosopyrimidine, an inactivator of O-6-alkylguanine-DNA alkyltransferase SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID LINKED AQUACOBALAMIN REDUCTASES; HUMAN TUMOR-CELLS; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA BCNU; CHLOROETHYLNITROSOUREA CYTOTOXICITY; 4-NITROQUINOLINE 1-OXIDE; ALKYLATING-AGENTS; CROSS-LINKING; O-6-BENZYLGUANINE; SENSITIVITY AB Inactivation of the human DNA repair protein, O-6-alkylguanine-DNA-alkyltransferase (AGT), by exposure to O-6-benzylguanine leads to a dramatic enhancement in the cytotoxic response of cells to chemotherapeutic alkylnitrosoureas, Benzylated pyrimidines identified as more potent inactivators than O-6-benzylguanine in vitro include 2,4-diamino-6-benzyloxy-5-nitrosopyrimidine (5-nitroso-BP) and 2,4-diamino-6-benzyloxy-5-nitropyrimidine (5-nitro-BP). In efforts to determine the clinical usefulness of these benzylated pyrimidines, we examined the metabolism and pharmacokinetics of 5-nitroso-BP in Sprague-Dawley rats, together with its potency as an AGT inactivator in mice, The mean plasma half-life, clearance, and volume of distribution of 5-nitroso-BP in rats were, respectively, 3.8 min, 22 liters/hr/kg, and 2.1 liters/kg. Two metabolites were identified in rat plasma (i.e. 5-nitro-BP and 2,4,5-triamino-6-benzyloxypyrimidine) after intravenous administration of 5-nitroso-BP in rat. Reduction of 5-nitroso-BP (100 mu M) occurred primarily in cytosol and was inhibited (>95%) by 1 mM menadione. Dicumarol (100 mu M), a DT-diaphorase inhibitor, did not significantly inhibit this reaction. This indicated a possible role of a dicumarol-resistant quinone reductase, At higher substrate and protein concentration, NADPH-dependent oxidation of 5-nitroso-BP to 5-nitro-BP primarily occurred in microsomes and was completely inhibited by 1-aminobenzotriazole (1 mM), a P450 inhibitor, Unfortunately, neither B-nitroso-BP nor 5-nitro-BP was as effective as O-6-benzylguanine at depleting AGT activity in mouse liver or spleen, At 1 hr after injection of 15 mg/kg O-6-benzylguanine, 5-nitroso-BP, or 5-nitro-BP, AGT levels in liver fell to 1%, 66%, and 71% basal activity, respectively, Rapid cytosolic reduction of 5-nitroso-BP may explain the lack of potency of the pyrimidines in vivo. C1 UNIV CHICAGO,DEPT MED,HEMATOL ONCOL SECT,CHICAGO,IL 60637. UNIV CHICAGO,CTR CANC RES,CHICAGO,IL 60637. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CO-46000, CA57725] NR 46 TC 8 Z9 9 U1 1 U2 5 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 NOV PY 1996 VL 24 IS 11 BP 1205 EP 1211 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VT357 UT WOS:A1996VT35700007 PM 8937854 ER PT J AU Selkirk, JK He, CY Patterson, RM Merrick, BA AF Selkirk, JK He, CY Patterson, RM Merrick, BA TI Tumor suppressor p53 gene forms multiple isoforms: Evidence for single locus origin and cytoplasmic complex formation with heat shock proteins SO ELECTROPHORESIS LA English DT Article DE tumor suppressor p53 gene; two-dimensional polyacrylamide gel electrophoresis; heat shock proteins; cell culture ID WILD-TYPE P53; TRANSFORMED-CELLS; MUTANT P53; SV40-TRANSFORMED CELLS; ACTIVATING MUTATIONS; T-ANTIGEN; GROWTH; MOUSE; HSP70; HSP90 AB The tumor suppressor protein p53 is a major cell cycle control factor, and mutations in p53 are the most common genetic lesion found in human tumors, resulting in loss of function and contributing to malignant transformation. This report reviews several studies which show that p53 protein appears as at least eleven isoforms having the same amino acid backbone but varying in charge by level of phosphorylation. All isoforms are derived from a single locus, which indicates that p53 activity is modulated by post-translational modification. In addition, mutant p53 forms hetero-oligomers with two families of proteins: HSP70 and a 90 kDa group similar to HSP90. Cytoplasmic complexes are most likely formed to protect p53 from proteolysis and are probably involved in translocation of activated p53 from the cytoplasm to the nucleus for transactivation of other cell cycle control genes. RP Selkirk, JK (reprint author), NIEHS,MOL CARCINOGENESIS LAB,111 ALEXANDER DR,RES TRIANGLE PK,NC 27709, USA. NR 45 TC 14 Z9 18 U1 0 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD NOV PY 1996 VL 17 IS 11 BP 1764 EP 1771 DI 10.1002/elps.1150171114 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA VY258 UT WOS:A1996VY25800013 PM 8982609 ER PT J AU Boll, W Ohno, H Zhou, SY Rapoport, I Cantley, LC Bonifacino, JS Kirchhausen, T AF Boll, W Ohno, H Zhou, SY Rapoport, I Cantley, LC Bonifacino, JS Kirchhausen, T TI Sequence requirements for the recognition of tyrosine-based endocytic signals by clathrin AP-2 complexes SO EMBO JOURNAL LA English DT Article DE adaptors; clathrin-associated proteins; coated vesicles; endocytosis; protein sorting ID TRANS-GOLGI NETWORK; TRANSFERRIN RECEPTOR INTERNALIZATION; FACTOR-II RECEPTOR; CYTOPLASMIC DOMAIN; COATED PITS; PROTEIN; LOCALIZATION; BINDING; TRAFFICKING; ADAPTORS AB We recently determined that fusion proteins containing tyrosine-based endocytic signals bind to the mu 2 subunit of AP-2, the complex that drives clathrin coat formation and mediates endocytosis from the plasma membrane, Here we analyze the selectivity of peptide recognition by mu 2 and by AP-2 using combinatorial selection methods and surface plasmon resonance, Both mu 2 and AP-2 are shown to interact with various sequences of the form tyrosine-polar-polar-hydrophobic (YppO) found on receptors that follow the clathrin pathway. The optimal sequence for interaction with mu 2 and with AP-2 has tyrosine as an anchor and prefers arginine at position Y+2 and leucine at position Y+3. In contrast, no preferred sequence is detected surrounding the YppO signal, indicating that recognition of the YppO endocytic signal does not require a prefolded structure. We conclude that sorting into the endocytic pathway is governed by a surprisingly simple interaction between the mu 2 chain and a tyrosine-containing tetrapeptide sequence. C1 HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892. BETH ISRAEL HOSP,DIV SIGNAL TRANSDUCT,BOSTON,MA 02115. RI Cantley, Lewis/D-1800-2014; Ohno, Hiroshi/L-7899-2014; OI Cantley, Lewis/0000-0002-1298-7653; Ohno, Hiroshi/0000-0001-8776-9661; Bonifacino, Juan S./0000-0002-5673-6370 FU NIGMS NIH HHS [R01 GM056203] NR 29 TC 226 Z9 227 U1 0 U2 3 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 NOV 1 PY 1996 VL 15 IS 21 BP 5789 EP 5795 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VR218 UT WOS:A1996VR21800006 PM 8918456 ER PT J AU Dimitrov, S Wolffe, AP AF Dimitrov, S Wolffe, AP TI Remodeling somatic nuclei in Xenopus laevis egg extracts: Molecular mechanisms for the selective release of histones H1 and H1 degrees from chromatin and the acquisition of transcriptional competence SO EMBO JOURNAL LA English DT Article DE chromatin; histone; transcriptional competence ID ERYTHROCYTE NUCLEI; DNA-REPLICATION; LINKER HISTONES; NUCLEOSOME MOBILITY; ASSEMBLY INVITRO; GLOBULAR DOMAIN; SPERM CHROMATIN; ACIDIC PROTEIN; MESSENGER-RNA; NUCLEOPLASMIN AB The molecular mechanisms responsible for the remodeling of entire somatic erythrocyte nuclei in Xenopus laevis egg cytoplasm have been examined. These transitions in chromosomal composition are associated with the capacity to activate new patterns of gene expression and the re-acquisition of replication competence, Somatic linker histone variants H1 and H1 degrees are released from chromatin in egg cytoplasm, whereas the oocyte-specific linker histone B4 and HMG1 are efficiently incorporated into remodeled chromatin. Histone H1 degrees is released from chromatin preferentially in comparison with histone H1, Core histones H2A and H4 in the somatic nucleus are phosphorylated during this remodeling process. These transitions recapitulate the chromosomal environment found within the nuclei of the early Xenopus embryo, Phosphorylation of somatic linker histone variants is demonstrated not to direct their release from chromatin, nor does direct competition with cytoplasmic stores of linker histone B4 determine their release. However, the molecular chaperone nucleoplasmin does have an important role in the selective removal of linker histones from somatic nuclei. For Xenopus erythrocyte nuclei, this disruption of chromatin structure leads to activation of the 5S rRNA genes, These results provide a molecular explanation for the remodeling of chromatin in Xenopus egg cytoplasm and indicate the capacity of molecular chaperones to disrupt a natural chromosomal environment, thereby facilitating transcription. C1 NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892. CNRS,INST ALBERT BONNIOT,LAB ETUD DIFFERENTIAT & ADHERENCE CELLULAIRE,UMR 5538,F-38706 LA TRONCHE,FRANCE. RI dimitrov, stefan/M-7697-2013 NR 64 TC 102 Z9 105 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 NOV 1 PY 1996 VL 15 IS 21 BP 5897 EP 5906 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VR218 UT WOS:A1996VR21800017 PM 8918467 ER PT J AU Merino, MJ Chuaqui, R Fernandez, P AF Merino, MJ Chuaqui, R Fernandez, P TI Parathyroid hemangioma: A report of two cases SO ENDOCRINE PATHOLOGY LA English DT Article DE parathyroid glands; hemangioma; angioma ID NECK; ANGIOSARCOMA; CARCINOMA AB Two cases of intraparathyroid hemangioma, associated with hyperparathyroidism, are reported. The first case showed a typical capillary hemangioma morphology with small branching vascular channels, almost completely replacing the gland's architecture. The second case was a 2-mm cavernous hemangioma associated with glandular hyperplasia. This is, to our knowledge, the first time that this type of lesion is described. C1 HOSP CLIN BARCELONA,BARCELONA,SPAIN. RP Merino, MJ (reprint author), NCI,PATHOL LAB,BLDG 10,RM 2N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 19 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 NOV PY 1996 VL 7 IS 4 BP 319 EP 322 DI 10.1007/BF02739839 PG 4 WC Endocrinology & Metabolism; Pathology SC Endocrinology & Metabolism; Pathology GA WA504 UT WOS:A1996WA50400009 ER PT J AU Eddy, EM Washburn, TF Bunch, DO Goulding, EH Gladen, BC Lubahn, DB Korach, KS AF Eddy, EM Washburn, TF Bunch, DO Goulding, EH Gladen, BC Lubahn, DB Korach, KS TI Targeted disruption of the estrogen receptor gene in male mice causes alteration of spermatogenesis and infertility SO ENDOCRINOLOGY LA English DT Article ID DUCTULI-EFFERENTES; EPIDIDYMAL SPERMATOZOA; ZONA PELLUCIDA; MOUSE TESTIS; RAT TESTIS; CELLS; FLUID; TESTOSTERONE; SERTOLI; FERTILIZATION AB The reproductive system of male mice homozygous for a mutation in the estrogen receptor (ER) gene (ER knock-out; ERKO) appears normal at the anatomical level. However, these males are infertile, indicating an essential role for ER-mediated processes in the regulation of male reproduction. Adult ERKO male mice have significantly fewer epididymal sperm than heterozygous or wild-type males. Although spermatogenesis is occurring in some seminiferous tubules of 3- to 5-month-old ERKO males, other tubules either have a dilated lumen and a disorganized seminiferous epithelium with few spermatogenic cells or lack a lumen and contain mainly Sertoli cells. There are no obvious differences in seminiferous tubules at 10 days of age between wild-type and ERKO mice, but the lumen in ERKO males is dilated in all seminiferous tubules by 20 days. However, spermatogenesis progresses and similar numbers of sperm are present in the cauda epididymis of ERKO and wild-type males until 10 weeks of age. Disruption of spermatogenesis and degeneration of the seminiferous tubules become apparent after 10 weeks in the caudal pole of the testis and progresses in a wave to the cranial pole by 6 months. However, the seminal vesicles, coagulating glands, prostate, and epididymis do not appear to be altered morphologically in ERKO mice. Serum testosterone levels are somewhat elevated, but LW and FSH levels are not significantly different from those in wild-type males. Sperm from 8- to 18-week-old mice have reduced motility and are ineffective at fertilizing eggs in vitro, In addition, ERKO males housed overnight with hormone-primed wild-type females produce significantly fewer copulatory plugs than do heterozygous or wild-type males. These results suggest that estrogen action is required for fertility in male mice and that the mutation of the ER in ERKO males leads to reduced mating frequency, low sperm numbers, and defective sperm function. C1 NIEHS, RECEPTOR BIOL SECT, REPROD & DEV TOXICOL LAB, NIH, RES TRIANGLE PK, NC 27709 USA. UNIV MISSOURI, DEPT BIOCHEM, COLUMBIA, MO 65211 USA. UNIV MISSOURI, DEPT CHILD HLTH, COLUMBIA, MO 65211 USA. RP Eddy, EM (reprint author), NIEHS, REPROD & DEV TOXICOL LAB, GAMETE BIOL SECT, NIH, MAIL DROP C4-01, RES TRIANGLE PK, NC 27709 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 49 TC 592 Z9 619 U1 4 U2 19 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 NOV PY 1996 VL 137 IS 11 BP 4796 EP 4805 DI 10.1210/en.137.11.4796 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VN809 UT WOS:A1996VN80900037 PM 8895349 ER PT J AU Zhou, J Adesanya, OO Vatzias, G Hammond, JM Bondy, CA AF Zhou, J Adesanya, OO Vatzias, G Hammond, JM Bondy, CA TI Selective expression of insulin-like growth factor system components during porcine ovary follicular selection SO ENDOCRINOLOGY LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; FACTOR-BINDING PROTEIN-2; GRANULOSA-CELLS INVITRO; I IGF-I; GENE-EXPRESSION; RAT OVARY; ESTROUS-CYCLE; LOCALIZATION; FOLLICLES; GONADOTROPINS AB In situ hybridization was used to map anatomical patterns of insulin-like growth factor (IGF) system gene expression in the gilt ovary through the estrous cycle. IGF-I, IGF-II, and IGF-I receptor messenger RNAs (mRNAs) were coexpressed in granulosa cells of developing and dominant follicles through the follicular phase. IGF-I and IGF-I receptor mRNAs were selectively concentrated in healthy follicles, whereas IGF-II mRNA was found in all follicles regardless of incipient or overt atresia. IGF-binding protein-1 (IGFBP-1) was not detected in the gilt ovary at any stage. IGFBP-2 mRNA was most abundant in granulosa cells of small follicles and in the ovarian vasculature regardless of cycle stage. IGFBP-2 mRNA persisted in granulosa cells of prevulatory follicles and corpora lutea. IGFBP-3 mRNA was not detected in developing follicles, but was detected in all luteal phase corpora lutea, apparently expressed by theca lutein cells. IGFBP-4 demonstrated a highly dynamic pattern of gene expression, closely tracking LH receptor gene expression throughout the follicular and luteal phases of the estrous cycle. IGFBP-4 mRNA was concentrated in the theca of medium to large growing follicles, but was not detected in granulosa cells until the emergence of dominant follicles in the late follicular stage, when the granulosa cells showed morphological evidence of luteinization as well as LH receptor gene expression. IGFBP-4 mRNA expression continued in granulosa cells of corpora lutea during the luteal phase and was not detected in atretic follicles. IGFBP-5 mRNA was concentrated in the surface or germinal epithelium and in capillary endothelium, particularly in capillaries of corpora lutea. In summary, there is selective expression of IGF-I, IGF-I receptor, and IGFBP-2 and -4 mRNAs during the process of follicular selection in the gilt ovary, with IGFBP-4 expression being closely associated with follicular selection and luteinization. These observations support an important role for autocrine/paracrine IGF action modulated by IGFBP-2 and 4 in both follicular growth and differentiation in the porcine ovary. C1 PENN STATE UNIV, DEPT DAIRY & ANIM SCI, UNIVERSITY PK, PA 16802 USA. PENN STATE UNIV, MILTON S HERSHEY MED CTR, DEPT MED, DIV ENDOCRINOL DIABET & METAB, HERSHEY, PA 17033 USA. RP Zhou, J (reprint author), NICHHD, DEV ENDOCRINOL BRANCH,NIH,BLDG 10,ROOM 10N262, 10 CTR DR, BETHESDA, MD 20892 USA. NR 27 TC 49 Z9 50 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 NOV PY 1996 VL 137 IS 11 BP 4893 EP 4901 DI 10.1210/en.137.11.4893 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VN809 UT WOS:A1996VN80900050 PM 8895362 ER PT J AU Cawley, NX Pu, LP Loh, YP AF Cawley, NX Pu, LP Loh, YP TI Immunological identification and localization of yeast aspartic protease 3-like prohormone-processing enzymes in mammalian brain and pituitary SO ENDOCRINOLOGY LA English DT Article ID OPIOMELANOCORTIN-CONVERTING ENZYME; SECRETORY VESICLES; INTERMEDIATE LOBE; BETA-LIPOTROPIN; MESSENGER-RNA; RAT-BRAIN; NEURONS; MEMBRANE; PROOPIOMELANOCORTIN; PRECURSOR AB The novel aspartic proteases, yeast aspartic protease 3 and the mammalian POMC-converting enzyme (PCE), can process prohormones at specific basic residue cleavage sites. We show that an antibody against yeast aspartic protease 3 (YAP3p) cross-reacted with purified bovine PCE on Western blot, indicating structural homology between these two enzymes, but not with other aspartic proteases, such as renin or cathepsin D. A PCE-sized anti-YAP3p-immunoreactive band was detected on Western blots of bovine intermediate lobe where PCE activity has been found. YAP3p antiserum also crossreacted with a protein of similar to 90 kDa from mouse hypothalamus and anterior pituitary, and bovine anterior pituitary secretory granules. Distribution studies showed the presence of anti-YAP3p-immunopositive cells in bovine pituitary and peptide-rich brain regions, including the mouse arcuate nucleus and hippocampus and the rat supraoptic nucleus, paraventricular nucleus, cortex, striatum, and reticular nucleus. In the bovine intermediate pituitary, a subpopulation of cells was intensely stained with the YAP3p antiserum, and in combination with in situ hybridization, these cells were shown to contain POMC messenger RNA (mRNA). Only a subpopulation of cells was immunopositive for anti-YAP3p in bovine anterior pituitary, and most of these cells were identified by double immunostaining with ACTH antiserum as corticotrophs. In situ hybridization in combination with immunocytochemistry provided evidence for the localization of arginine vasopressin mRNA in YAP3p-immunopositive neurons in the rat supraoptic nucleus, whereas cholecystokinin mRNA was detected in YAP3p-immunopositive cells in the rat cortex and hippocampus. These results support the hypothesis that YAP3p-like aspartic proteases, including PCE, play a role in prohormone processing in endocrine/neuroendocrine cells in vivo. C1 NICHHD, CELLULAR NEUROBIOL SECT, DEV NEUROBIOL LAB, NIH, BETHESDA, MD 20892 USA. NR 48 TC 19 Z9 19 U1 1 U2 1 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 NOV PY 1996 VL 137 IS 11 BP 5135 EP 5143 DI 10.1210/en.137.11.5135 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VN809 UT WOS:A1996VN80900076 PM 8895388 ER PT J AU Cooper, GS Sandler, DP Whelan, EA Smith, KR AF Cooper, GS Sandler, DP Whelan, EA Smith, KR TI Association of physical and behavioral characteristics with menstrual cycle patterns in women age 29-31 years SO EPIDEMIOLOGY LA English DT Article DE menstrual cycles; bleeding; smoking; weight; height; alcohol drinking; physical activity; caffeine ID BREAST-CANCER; CIGARETTE-SMOKING; UNITED-STATES; RISK; CONTRACEPTION; CONSUMPTION; ESTROGEN; ALCOHOL; WEIGHT AB We examined the association between menstrual cycle characteristics (cycle length, variability, and bleeding length) and physical and behavioral attributes in 766 women age 29-31 years. Menstrual cycle data were prospectively recorded as part of the Menstruation and Reproductive History Study of college women in Minnesota, begun by Alan Treloar in 1934. Data on lifetime height, weight, physical activity, alcohol and caffeine consumption, and smoking history were collected in 1990 using a self-administered questionnaire. Cycle variability, as measured by the standard deviation of the cycle length, was increased, and menstrual cycles greater than or equal to 42 days in length were more common among women in the lowest quartile of Quetelet index [odds ratio (OR) for long cycle = 1.6; 95% confidence interval (CI) = 0.82-3.0] and among the most physically active (OR = 1.7; 95% CI = 0.93-3.1). Long menstrual cycles were less common (OR = 0.40; 95% CI = 0.22-0.73) among women who drank alcohol than among nondrinkers. Variable or long menstrual cycles may reflect anovulation and relatively low levels of estrogen exposure. We would expect, based on our data, reduced estrogen exposure among lean women, physically active women, and those who do not consume alcohol. These findings suggest an explanation for the reported associations between these factors and breast cancer risk. RP Cooper, GS (reprint author), NIEHS,EPIDEMIOL BRANCH,A3-05,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Sandler, Dale/0000-0002-6776-0018 NR 32 TC 63 Z9 65 U1 0 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 1996 VL 7 IS 6 BP 624 EP 628 DI 10.1097/00001648-199611000-00010 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VN283 UT WOS:A1996VN28300011 PM 8899389 ER PT J AU Bialer, M Johannessen, SI Kupferberg, HJ Levy, RH Loiseau, P Perucca, E AF Bialer, M Johannessen, SI Kupferberg, HJ Levy, RH Loiseau, P Perucca, E TI Progress report on new antiepileptic drugs: A summary of the Third Eilat Conference SO EPILEPSY RESEARCH LA English DT Editorial Material DE antiepileptic drug development; clinical trial design; drug approval ID NEWLY-DIAGNOSED EPILEPSY; CARBAMAZEPINE; CLOBAZAM; PROFILE AB The Third Eilat Conference on New Antiepileptic Drugs was held at the Royal Beach Hotel from May 27 to May 30, 1996. Epileptologists and scientists from 20 countries attended the conference, which was held to discuss critical issues in drug development, new antiepileptic drugs (AEDs) in development, progress reports and recent findings of newly marketed AEDs, the use of AEDs in special populations and their utilization in non-epileptic disorders. Over the last seven years, six new AEDs have been introduced worldwide and new information on their safety and efficacy has become available. These include felbamate, gabapentin, lamotrigine, oxcarbazepine, topiramate and vigabatrin. Drugs in development include those at an advanced stage, such as remacemide and tiagabine, as well as those just entering clinical trials, such as rufinamide (CGP 331010) and levetiracetam (ucb LO59). The following is a summary of the presentations for drugs in development and recent findings on newly marketed drugs. C1 NATL CTR EPILEPSY,SANDVIKA,NORWAY. NINCDS,EPILEPSY BRANCH,NIH,BETHESDA,MD 20892. UNIV WASHINGTON,DEPT PHARMACEUT,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT NEUROL SURG,SEATTLE,WA 98195. UNIV BORDEAUX 1,HOSP PELLEGRIN,DEPT NEUROL,BORDEAUX,FRANCE. UNIV PAVIA,DEPT INTERNAL MED & THERAPEUT,CLIN PHARMACOL UNIT,I-27100 PAVIA,ITALY. RP Bialer, M (reprint author), HEBREW UNIV JERUSALEM,FAC MED,SCH PHARM,IL-91120 JERUSALEM,ISRAEL. NR 40 TC 36 Z9 36 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD NOV PY 1996 VL 25 IS 3 BP 299 EP 319 DI 10.1016/S0920-1211(96)00081-2 PG 21 WC Clinical Neurology SC Neurosciences & Neurology GA VV202 UT WOS:A1996VV20200020 PM 8956930 ER PT J AU Jean, P LopezGarcia, P Dansette, P Mansuy, D Goldstein, JA AF Jean, P LopezGarcia, P Dansette, P Mansuy, D Goldstein, JA TI Oxidation of tienilic acid by human yeast-expressed cytochromes P-450 2C8, 2C9, 2C18 and 2C19 - Evidence that this drug is a mechanism-based inhibitor specific for cytochrome P-450 2C9 SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE ionic strength; covalent binding; tienilic acid; cytochromes P-450 2C; suicide inhibition ID HUMAN-LIVER-MICROSOMES; (S)-MEPHENYTOIN 4'-HYDROXYLASE; MEPHENYTOIN HYDROXYLATION; SACCHAROMYCES-CEREVISIAE; CYP2C SUBFAMILY; TOLBUTAMIDE; METABOLITES; ENZYME; DERIVATIVES; BINDING AB Oxidation of tienilic acid by human cytochromes P-450 (CYP) 2C9, 2C18, 2C8 and 2C19 was studied using recombinant enzymes expressed in yeast. CYP 2C9 was the best catalyst for 5-hydroxylation of tienilic acid (K-m = 5 +/- 1 mu M, k(cat) = 1.7 +/- 0.2 min(-1)), 30-fold more potent in terms of k(cat)/K-m than CYP 2C18 (K-m = 150 +/- 15 mu M, k(cat) = 1.8 +/- 0.2 min(-1)) and 300-fold more potent than CYP 2C8 (K-m = 145 +/- 15 mu M, k(cat) = 0.2 +/- 0.1 min(-1)). CYP 2C19 was unable to catalyze this hydroxylation under our experimental conditions. During this study, a marked effect of the ionic strength on the activities (hydroxylations of tienilic acid and tolbutamide) of these cytochromes P-450 expressed in the yeast strain 334 was observed. The effect was particula!ly great in the case of CYP 2C18, with a tenfold decrease of activity upon increasing ionic strength from 0.02 to 0.1. Specific-covalent binding of tienilic acid metabolites to cytochrome P-450 (incubations in the presence of 5 mM glutathione) was markedly higher upon tienilic acid oxidation by CYP 2C9 than by CYP 2C18 and CYP 2C8. Mechanism-based inactivation of cytochrome P-450 during tienilic acid oxidation was observed in the case of CYP 2C9 but was not detectable with CYP 2C18 and CYP 2C8. Tienilic acid thus appears to be a mechanism-based inhibitor specific for CYP 2C9 in human liver. Experiments performed with human liver microsomes confirmed that tienilic acid 5-hydroxylase underwent a time-dependent inactivation (apparent t(1/2) = 10 +/- 5 min) during 5-hydroxylation of tienilic acid. C1 UNIV PARIS 05, CHIM & BIOCHIM PHARMACOL & TOXICOL LAB, CNRS, URA 400, F-75270 PARIS 06, FRANCE. UNIV VALENCIA, FAC FARM, DEPT BIOQUIM & BIOL MOL, E-46003 VALENCIA, SPAIN. NIEHS, RES TRIANGLE PK, NC 27709 USA. RI Goldstein, Joyce/A-6681-2012; DANSETTE, Patrick/B-8384-2014 NR 33 TC 47 Z9 50 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD NOV 1 PY 1996 VL 241 IS 3 BP 797 EP 804 DI 10.1111/j.1432-1033.1996.00797.x PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VR384 UT WOS:A1996VR38400014 PM 8944768 ER PT J AU Johnston, PG Geoffrey, F Drake, J Voeller, D Grem, JL Allegra, CJ AF Johnston, PG Geoffrey, F Drake, J Voeller, D Grem, JL Allegra, CJ TI The cellular interaction of 5-fluorouracil and cisplatin in a human colon carcinoma cell line SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE 5-fluorouracil; cisplatin; human colon carcinoma ID THYMIDYLATE SYNTHETASE; BIOCHEMICAL DETERMINANTS; FLUOROURACIL; CANCER; COMBINATION; INVIVO; HEAD; MICE; ADENOCARCINOMAS; CHEMOTHERAPY AB The combination of 5-fluorouracil (5-FU) and cisplatin (CDDP) has been shown to have synergistic cytotoxicity in human tumours, but the biochemical mechanism for this interaction remains unclear. Therefore, the aim of this study was to investigate the interaction of 5-FU and CDDP in a human colon carcinoma cell line, NCI H548. A 24 h exposure to 5-FU resulted in a 5-FU IC50 value of 24.2 +/- 4.5 mu M, Dm 22.6 mu M; exposure to COOP for 2 h resulted in a IC50 value of 20.8 +/- 8.0 mu M, Dm 21.9 mu M. When cells were exposed simultaneously to 5-FU for 24 h and CDDP for the initial 2 h, or when cells were treated with CDDP for 2 h followed by various concentrations of 5-FU for 24 h, no greater than additive cytotoxicity was observed. In contrast, when cells were treated with 5-FU for 24 h prior to CDDP for 2 h, a greater than additive interaction was noted (5-FU IC50 1.2 +/- 0.6 mu M, Dm 1.3 mu M, CI 0.45). Thymidine 10 mu M partially reversed the growth inhibitory effects of the 5-FU/CDDP combination. Using both immunological and biochemical assays, no notable differences in the total amount of TS enzyme or the fraction of bound TS enzyme could be detected in the absence or presence of CDDP. No notable differences could be detected in intracellular reduced folate pools, FdUMP or FUTP pools, or 5-FU incorporation into RNA or DNA with the addition of CDDP to 5-FU. DNA fragmentation studies revealed that the combination of 5-FU followed by CDDP demonstrated a greater degree of single-stranded DNA fragments in parental (P = 0.024) and newly synthesised DNA (P = 0.025) compared with the administration of CDDP prior to 5-FU or either drug alone. The increase in smaller DNA fragment size was reversed with the addition of thymidine (10 mu M). These findings suggest that the interaction of 5-FU and CDDP is associated with a greater degree of fragmentation of both nascent and parental DNA. C1 NCI,NAVY MED ONCOL BRANCH,NIH,BETHESDA,MD 20892. NR 36 TC 33 Z9 33 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 1996 VL 32A IS 12 BP 2148 EP 2154 DI 10.1016/S0959-8049(96)00266-3 PG 7 WC Oncology SC Oncology GA VY965 UT WOS:A1996VY96500033 PM 9014759 ER PT J AU Mumford, GK Benowitz, NL Evans, SM Kaminski, BJ Preston, KL Sannerud, CA Silverman, K Griffiths, RR AF Mumford, GK Benowitz, NL Evans, SM Kaminski, BJ Preston, KL Sannerud, CA Silverman, K Griffiths, RR TI Absorption rate of methylxanthines following capsules, cola and chocolate SO EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE caffeine; cocoa; chocolate; theobromine; methylxanthines; absorption; humans ID CAFFEINE; PHARMACOKINETICS; THEOBROMINE; DISPOSITION; METABOLITES; HUMANS AB Objective: To compare caffeine and theobromine absorption after oral administration of capsules, cola beverage and chocolate candy. Methods: Three males and four females who abstained from methylxanthines received five methylxanthine-containing treatments: caffeine in capsules (72 mg), administered twice; theobromine in capsules (370 mg); cola beverage (72 mg caffeine) and chocolate candy (72 mg caffeine and 370 mg theobromine). Plasma methylxanthine levels were assayed from samples collected before and 0.25, 0.50, 0.75, 1.0, 1.5, 2.0, and 3.0 h after caffeine capsule and cola treatments and, additionally, at 4.0 and 6.0 h after theobromine capsule and chocolate treatments. Results: Caffeine plasma concentrations increased rapidly and peaked at approximately 30 min following both capsule treatments 1 (C-max: 1.93 mu g . ml(-1)); and 2 (C-max: 2.05 mu g . ml(-1)). Relative to capsules, caffeine absorption from cola and chocolate was delayed and produced lower maximum caffeine plasma concentrations which peaked 1.5-2.0 h after treatment (For cola, C-max: 1.57 mu g . ml(-1)); and for chocolate, C-max: 1.50 mu g . ml(-1). Theobromine plasma concentrations peaked approximately 3 h after capsule administration (C-max: 6.72 mu g . ml(-1)). Relative to capsules, theobromine absorption from chocolate was more rapid and produced higher maximum theobromine plasma concentrations which peaked approximately 2 h after treatment (C-max: 8.05 mu g . ml(-1)). Conclusions: The results suggest that a usual dietary portion of the cola or chocolate used in this study would produce behaviorally discriminable plasma levels of caffeine in most subjects and of theobromine in at least one subject. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BEHAV BIOL RES CTR,BALTIMORE,MD 21224. NIDA,ADDICT RES CTR,CLIN PHARMACOL BRANCH,BALTIMORE,MD 21224. NIDA,ADDICT RES CTR,TREATMENT BRANCH,BALTIMORE,MD 21224. NIDA,ADDICT RES CTR,PRECLIN PHARMACOL LAB,BALTIMORE,MD 21224. NIDA,ADDICT RES CTR,DEPT NEUROSCI,BALTIMORE,MD 21224. SAN FRANCISCO GEN HOSP,MED CTR,DIV CLIN PHARMACOL & EXPT THERAPEUT,SAN FRANCISCO,CA 94110. RI Preston, Kenzie/J-5830-2013; OI Preston, Kenzie/0000-0003-0603-2479; Silverman, Kenneth/0000-0003-2724-1413 FU NIDA NIH HHS [R01 DA01696, R01 DA03890] NR 21 TC 41 Z9 42 U1 1 U2 14 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0031-6970 J9 EUR J CLIN PHARMACOL JI Eur. J. Clin. Pharmacol. PD NOV-DEC PY 1996 VL 51 IS 3-4 BP 319 EP 325 DI 10.1007/s002280050205 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WA510 UT WOS:A1996WA51000023 PM 9010706 ER PT J AU Yu, YM Domene, HM Sztein, J Counts, DR Cassorla, F AF Yu, YM Domene, HM Sztein, J Counts, DR Cassorla, F TI Developmental changes and differential regulation by testosterone and estradiol of growth hormone receptor expression in the rabbit SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID GH-BINDING-PROTEIN; GENE-EXPRESSION; PULSE AMPLITUDE; HUMAN PLASMA; FACTOR-I; RAT; SERUM; PUBERTY; SECRETION; STEROIDS AB To investigate the effects of testosterone and estradiol (E(2)) on growth hormone receptor (GH-R) gene expression, we measured GH-R mRNA levels in relation to the changes of sex steroid concentrations in the normal male rabbits aged 1-12 months and after administration of testosterone or E(2) to castrated male rabbits. In the normal animals, E(2) levels were below the detection limit in all age groups, and testosterone levels were below the detection limit at 1 month, increased at 2 months and reached the plateau of the adult levels after 4 months. Liner GH-R mRNA levels were low at 1 month, reached a peak at 2 months and then decreased slightly thereafter. In the castrated animals, liner and growth plate GH-R mRNA levels were increased in the testosterone-treated group (162.0 +/- 12.0%, p < 0.025; 128.4 +/- 7.6%; p < 0.025) and reduced in the E(2)-treated group (29.6 +/- 6.2%, p < 0.005; 53.6 +/- 11.3%, p < 0.025). Sex steroid administration did not result in any significant change in GH-R mRNA levels in striated muscle, kidney and heart. Serum GH concentrations were increased in E(2) (15.3 +/- 7.7 mu g/l vs 4.8 +/- 2.2 mu g/l, p < 0.025) but the increase was not significant in testosterone-treated animals (8.4 +/- 7.7 mu g/l vs 4.8 +/- 2.2 mu g/l). Both testosterone and E(2) treatment resulted in a reduction of mean serum growth hormone-binding protein (GHBP) levels compared to control animals (1077 +/- 422 pmol/l, p < 0.01; 1137 +/- 443 pmol/l, p < 0.01; 2308 +/- 565 pmol/l). We conclude that in addition to their stimulatory effect on GK secretion, testosterone and E(2) have opposite effects on GH-R gene expression in liver and growth plate in the rabbit. The modulation of GH-R expression by sex steroids may be important for growth during sexual maturation in mammals. C1 NICHHD, NIH, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. UNIV MARYLAND, SCH MED, DEPT PEDIAT, BALTIMORE, MD 21201 USA. HOSP NINOS DR RICARDO GUTIERREZ, CTR INVEST ENDOCRINOL, BUENOS AIRES, DF, ARGENTINA. NEI, NIH, VET RESOURCES SECT, BETHESDA, MD 20892 USA. UNIV CHILE, HOSP SAN BORJA ARRIARAN, INST INVEST MATERNOINFANTIL, SANTIAGO, CHILE. RI Sztein, Jorge/B-7165-2012 NR 29 TC 17 Z9 20 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD NOV PY 1996 VL 135 IS 5 BP 583 EP 590 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VW088 UT WOS:A1996VW08800012 PM 8980161 ER PT J AU Vergelli, M Hemmer, B Utz, U Vogt, A Kalbus, M Tranquill, L Conlon, P Ling, N Steinman, L McFarland, HF Martin, R AF Vergelli, M Hemmer, B Utz, U Vogt, A Kalbus, M Tranquill, L Conlon, P Ling, N Steinman, L McFarland, HF Martin, R TI Differential activation of human autoreactive T cell clones by altered peptide ligands derived from myelin basic protein peptide (87-99) SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE human; autoimmunity; T lymphocyte; myelin basic protein; altered peptide ligands ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; COMPLEMENTARITY-DETERMINING REGION-3; MULTIPLE-SCLEROSIS PATIENTS; RECEPTOR LIGAND; HLA-DR; RECOGNITION; SPECIFICITY; COMPLEXES; MOLECULES; EPITOPE AB We have examined the functional consequences induced by interaction of DR2a-restricted myelin basic protein (MBP) (87-99)-specific T cell clones (TCC) with altered peptide ligands (APL) derived from MBP peptide (87-99). The immunodominant MBP peptide (87-99) has been implicated as a candidate antigen in multiple sclerosis (MS) by several lines of evidence. In the present study, we have defined the T cell receptor (TCR) contact residues for DR2a-restricted, (87-99)-specific T helper type 1 T cells to design APL suitable to modify the functions of such T cells potentially relevant for the pathogenesis of MS. We show that neutral (L-alanine substitutions) or conservative exchanges of the primary and secondary TCR contact residues lead to various alterations of T cell function, ranging from differences in interleukin-2 receptor up-regulation to anergy induction and TCR antagonism. The potential usefulness of APL as an immunomodulating therapy for DR2(+) MS patients is discussed. C1 NINCDS,NEUROIMMUNOL BRANCH,NIH,BETHESDA,MD 20892. GERMAN CANC RES CTR,DIV SOMAT GENET,TUMOR IMMUNOL PROGRAM,D-6900 HEIDELBERG,GERMANY. NEUROCRINE BIOSCI INC,SAN DIEGO,CA. UNIV TUBINGEN,SCH MED,DEPT NEUROL,TUBINGEN,GERMANY. STANFORD UNIV,SCH MED,DEPT NEUROL,STANFORD,CA. WEIZMANN INST SCI,DEPT CELL BIOL,IL-76100 REHOVOT,ISRAEL. NR 35 TC 89 Z9 89 U1 0 U2 1 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 NOV PY 1996 VL 26 IS 11 BP 2624 EP 2634 DI 10.1002/eji.1830261113 PG 11 WC Immunology SC Immunology GA VT775 UT WOS:A1996VT77500012 PM 8921948 ER PT J AU Vlachova, V Zemkova, H Vyklicky, L AF Vlachova, V Zemkova, H Vyklicky, L TI Copper modulation of NMDA responses in mouse and rat cultured hippocampal neurons SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE copper; zinc; glutamate receptor; N-methyl-D-aspartate receptor; hippocampus ID METHYL-D-ASPARTATE; AMINO-ACID RECEPTORS; ACTIVATED CHANNELS; DIVALENT-CATIONS; CORTICAL-NEURONS; BRAIN REGIONS; SPINAL-CORD; ZINC; CURRENTS; ANTAGONISTS AB The effect of Cu2+ on NMDA receptors was studied in cultured mouse and rat hippocampal neurons using whole-cell patch-clamp and a fast perfusion system. Analysis of the Cu2+ concentration-response curve for inhibition of NMDA-induced currents suggests that free Cu2+ directly inhibits NMDA receptors with an IC50 of 0.27 mu M. Cu2+ was ineffective in blocking NMDA receptor activity when complexed with NMDA or glycine; NMDA-Cu2+ and glycine-Cu2+ complexes acted as agonists of similar potency to the free amino acids. The inhibition by Cu2+ (10-100 mu M) of responses to 10 mu M NMDA was essentially voltage-independent. The onset of inhibition by 100 mu M Cu2+ of responses to 2 mu M glutamate acting at NMDA receptors was significantly faster than NMDA receptor deactivation evoked by a sudden decrease in the concentration of glycine or glutamate, or of both agonists. This suggests that Cu2+ acts as a non-competitive antagonist, and does not directly interfere with the binding of glutamate or glycine to their recognition sites on the NMDA receptor complex. In the absence of NMDA the apparent association rate constant for binding of Cu2+ to NMDA receptors, calculated from the rate of onset of block by Cu2+ of test responses to NMDA, was 19 times slower than in the presence of 30 mu M NMDA, suggesting that Cu2+ interacts preferentially with agonist-bound receptors. Our results show that Cu2+ is a potent inhibitor of NMDA receptor-mediated responses. C1 ACAD SCI CZECH REPUBL,INST PHYSIOL,CR-14220 PRAGUE 4,CZECH REPUBLIC. NICHHD,LAB CELLULAR & MOL NEUROPHYSIOL,NIH,BETHESDA,MD 20892. RI Vlachova, Viktorie/A-4380-2012; Zemkova, Hana/C-1844-2012; Vyklicky, Ladislav/C-1851-2012 OI Vyklicky, Ladislav/0000-0002-0015-0098 NR 34 TC 65 Z9 65 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD NOV PY 1996 VL 8 IS 11 BP 2257 EP 2264 DI 10.1111/j.1460-9568.1996.tb01189.x PG 8 WC Neurosciences SC Neurosciences & Neurology GA WD020 UT WOS:A1996WD02000005 PM 8950090 ER PT J AU Tirindelli, R Ryba, NJP AF Tirindelli, R Ryba, NJP TI The G-protein gamma-subunit G gamma 8 is expressed in the developing axons of olfactory and vomeronasal neurons SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE olfactory; vomeronasal; G-proteins; immunocytochemistry; neurogenesis; signal transduction ID ODORANT RECEPTOR EXPRESSION; GROWTH CONE; SIGNAL TRANSDUCTION; NEURAL DEVELOPMENT; GENE-EXPRESSION; EPITHELIUM; SYSTEM; RAT; ADULT; CELLS AB The tissue localization of the G-protein gamma-subunit, G gamma 8, that is specifically expressed in the olfactory and vomeronasal neurons, was studied in rats at different ages: embryonic day 16, postnatal days 1, 7, 14 and 35, and adult. G8 appears to be a specific marker of the immature olfactory and vomeronasal neurons. Its distribution differs from that of Golf alpha, a G-protein alpha-subunit which is predominantly expressed in mature olfactory neurons. G8 immunoreactivity indicates that an undifferentiated organization of the olfactory epithelium persists up to 3 weeks of age, though neonates possess a functional sense of smell. G gamma 8 accumulates at the highest levels in the axons of the developing olfactory neurons 2 weeks after birth (postnatal day 14). Moreover, up to postnatal day 14, G gamma 8-positive neurons are present in the region of the olfactory and vomeronasal epithelium, where they are not observed in later life. In the olfactory epithelium and in the bulb, G gamma 8 expression becomes weaker and patchy with increasing age, suggesting that the process of continuous regeneration of olfactory neurons occurs in discrete areas. G8-enhanced expression following axotomy indicates that this system is potentially active throughout life. Conversely, in the vomeronasal epithelium G gamma 8 expression persists virtually unmodified in the adult. This indicates that the degree of differentiation may differ between olfactory and vomeronasal neurons. C1 NIDR,IMMUNOL LAB,NIH,BETHESDA,MD 20892. RP Tirindelli, R (reprint author), UNIV PARMA,IST FISIOL UMANA,VIA GRAMSCI 14,I-43100 PARMA,ITALY. NR 42 TC 19 Z9 20 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD NOV PY 1996 VL 8 IS 11 BP 2388 EP 2398 DI 10.1111/j.1460-9568.1996.tb01202.x PG 11 WC Neurosciences SC Neurosciences & Neurology GA WD020 UT WOS:A1996WD02000018 PM 8950102 ER PT J AU Stratakis, CA Chrousos, GP AF Stratakis, CA Chrousos, GP TI Transient elevation of serum thyroid hormone levels following lithium discontinuation SO EUROPEAN JOURNAL OF PEDIATRICS LA English DT Article DE thyroid gland; lithium; hyperthyroidism; adolescence; depression ID DISORDERS; HYPERTHYROIDISM; ABNORMALITIES AB Lithium therapy has been associated with altered thyroid function and even goiter in as many as half of chronically treated patients. We describe the case of a 16-year-old boy who developed transient hyperthyroxinemia after discontinuation of chronic lithium therapy. The lack of clinical hyperthyroidism and the gradual resolution of the biochemical abnormalities in this patient pointed to the benign character of his condition known as ''euthyroid hyperthyroxinemia''. Conclusion Euthyroid hyperthyroxinemia may be a benign, transient complication of lithium-therapy discontinuation and should be considered in the diagnostic evaluation of lithium-related thyroid abnormalities. RP Stratakis, CA (reprint author), GEORGETOWN UNIV,NIH,NICHD,DEB,BLDG 10,ROOM 10 N 262,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 17 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6199 J9 EUR J PEDIATR JI Eur. J. Pediatr. PD NOV PY 1996 VL 155 IS 11 BP 939 EP 941 DI 10.1007/BF02282883 PG 3 WC Pediatrics SC Pediatrics GA VN806 UT WOS:A1996VN80600006 PM 8911893 ER PT J AU Webels, H VonEye, A AF Webels, H VonEye, A TI Using latent class analysis to detect behavioral patterns in systems of observational variables SO EVALUATION AND PROGRAM PLANNING LA English DT Article ID DYADIC INTERACTION; MODELS; FRAMEWORK; ORIGINS; INFANT AB Behavioral observation is widely used for data gathering in evaluation research. Yet it leaves the investigator with unique problems. Usually, multiple observations result in a hierarchical data set, where numerous data records exist for each subject. Researchers face data reduction problems at least at two levels. First, there is the well-known and often-addressed problem of reducing the number of variables in a data set with only one information record per individual. Second, there is the problem of summarizing data at the individual subject level. The easiest way to perform this latter type of aggregation involves using univariate summary measures as probabilities of ''using'' an item, means, or standard deviations for each item per subject. Other standard procedures include first order interactions between pairs of items. However, Erse of pair-wise interactions is restricted because of variable dependence within each subject (this affects, e.g. factor analysis), or because of the relatively high number of single observations (this affects, e.g., cluster analysis). In this paper we propose employing Latent Class Analysis (LCA) to reduce the amount of information in observational data sets. In a first step, LCA allows one to specify intraindividual behavior patterns. In a second step, LCA allows one to derive meaningful summary scores for each individual. The two steps are illustrated using data that describe peer play competence in Swedish toddlers. Copyright (C) 1996 Elsevier Science Ltd C1 MICHIGAN STATE UNIV,E LANSING,MI 48824. RP Webels, H (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 48 TC 1 Z9 1 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0149-7189 J9 EVAL PROGRAM PLANN JI Eval. Program Plan. PD NOV PY 1996 VL 19 IS 4 BP 321 EP 331 DI 10.1016/S0149-7189(96)00030-4 PG 11 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA VZ904 UT WOS:A1996VZ90400005 ER PT J AU Arking, R Force, AG Dudas, SP Buck, S Baker, GT AF Arking, R Force, AG Dudas, SP Buck, S Baker, GT TI Factors contributing to the plasticity of the extended longevity phenotypes of Drosophila SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE longevity; life span; Drosophila; genetic control of aging; genetic plasticity; phenotypic plasticity; environment effects ID LONG-LIVED STRAIN; ELONGATION-FACTOR EF-1-ALPHA; ZN SUPEROXIDE-DISMUTASE; LIFE-SPAN; POSTPONED SENESCENCE; OXIDATIVE STRESS; ENVIRONMENT INTERACTION; QUANTITATIVE GENETICS; CORRELATED RESPONSES; LABORATORY EVOLUTION AB A number of laboratories have constructed independently derived long-lived strains of Drosophila, each of which have similar but not identical patterns of variability in their adult longevity. Given the observed plasticity of longevity within each of these strains, it would be useful to review the operational and environmental factors that give rise to this phenotypic plasticity and ascertain whether they are common or strain specific. Our review of the more extensively analyzed strains suggests that the allelic composition of the initial genomes and the selection/transgene strategy employed yield extended longevity strains with superficially similar phenotypes but which are probably each the result of different proximal genetic mechanisms. This then offers a plausible explanation for the differential effects of various environmental factors on each strain's particular pattern of phenotypic plasticity. It also illustrates that the species has the potential to employ any one of a number of different proximal mechanisms, each of which give rise to a similar longevity phenotype. Copyright (C) 1996 Elsevier Science Inc. C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP Arking, R (reprint author), WAYNE STATE UNIV,DEPT BIOL SCI,DETROIT,MI 48202, USA. FU NIA NIH HHS [AG 08834] NR 98 TC 23 Z9 23 U1 0 U2 1 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 NOV-DEC PY 1996 VL 31 IS 6 BP 623 EP 643 DI 10.1016/S0531-5565(96)00096-4 PG 21 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA VW471 UT WOS:A1996VW47100001 PM 9415093 ER PT J AU Talan, MI Kirov, SA Kosheleva, NA AF Talan, MI Kirov, SA Kosheleva, NA TI Nonshivering thermogenesis in adult and aged C57BL/6J mice housed at 22 degrees C and at 29 degrees C SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE body temperature; thermoregulation; brown adipose tissue; cold tolerance; heat production; rodents; sympathetic nervous activity; thermogenin; uncoupling protein ID BROWN ADIPOSE-TISSUE; SYMPATHETIC NERVOUS ACTIVITY; UNCOUPLING PROTEIN; GDP BINDING; COLD STRESS; OLD RATS; THERMOREGULATION; METABOLISM; EXPRESSION; RESPONSES AB Twelve- and 28-month-old C57BL/6J male mice were housed either at room temperature of 22 degrees C or at thermoneutrality (29 degrees C) during the two months prior to experiments. Acute experiments were conducted under anesthesia, myorelaxation, and artificial ventilation. We recorded efferent electrical impulse activity in one of the sympathetic nerves innervating the interscapular brown adipose tissue in response to acute cold stimulation, when body temperature was lowered 7.5 degrees C below control level. In separate experiments we measured O-2 consumption and CO2 production and calculated the nonshivering thermogenesis. We also measured the concentration of uncoupling protein in interscapular brown adipose tissue before and after three-hour cold stress. in aged mice, both sympathetic nervous activity and nonshivering thermogenesis were lower in animals housed at thermoneutrality (29 degrees C) than in mice housed at 22 degrees. Among mice maintained at 22 degrees C, but not at thermoneutrality, aged animals had greater nonshivering thermogenesis and greater cold induced concentration of uncoupling protein in the brown adipose tissue than adults. Sympathetic nervous outflow to brown adipose tissue was always greater in aged mice, regardless of the temperature of acclimation. We concluded that aged mice, housed at 22 degrees C, showed the changes in nonshivering thermogenesis associated with cold acclimation. However, an increased sympathetic outflow to brown adipose tissue in aged animals reflects an age-related elevation of the tone and responsiveness of the sympathetic nervous system. Copyright (C) 1996 Elsevier Science Inc. RP Talan, MI (reprint author), NIA,GERONTOL RES CTR,BEHAV SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 36 TC 12 Z9 12 U1 0 U2 1 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 NOV-DEC PY 1996 VL 31 IS 6 BP 687 EP 698 DI 10.1016/S0531-5565(96)00095-2 PG 12 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA VW471 UT WOS:A1996VW47100005 PM 9415097 ER PT J AU Kaya, M Chang, L Truong, A Brightman, MW AF Kaya, M Chang, L Truong, A Brightman, MW TI Chemical induction of fenestrae in vessels of the blood-brain barrier SO EXPERIMENTAL NEUROLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; MONOCLONAL-ANTIBODY; INVITRO MODULATION; RAT-TISSUES; CELLS; EXPRESSION; PERMEABILITY; COLLAGENASE; PROTEIN; METALLOPROTEINASES AB The endothelium responsible for the blood-brain barrier to hydrophilic solutes has been converted here, by chemical means, to the fenestrated, permeable type of vessel (FV). During development, some brain vessels are reported to be transiently fenestrated. Endothelial fenestrae of adrenal glands are known to be reinduced in vitro by retinoic acid (RA) or phorbol myristate acetate (PMA). Could fenestrae be likewise reinduced in brain barrier vessels? When RA or PMA were infused continuously by an osmotic pump for 28 days into the cerebral cortex of rats, some brain vessels in the lesion cavity created by the reagents were FV,There were no FV in adjacent brain, When 100 mu M RA was infused, about 20% of vessels in the cyst were FV, as were about 29% after infusion of 150 ng/ml PMA. Fenestra development depended on concentration and time. Reversibility of fenestra formation was complete at 1-2 months after delivery of RA or PMA had ceased. It is proposed that the RA and PMA effect is mediated by the plasminogen activator urokinase, in as much as both RA and PMA stimulate its production, This notion is supported by preliminary experiments in which urokinase infusion into brain also produced fenestrae, It is further suggested that the reversible induction of fenestrae in the mature brain by RA, PMA, and, perhaps, a variety of other conversion factors may be confined to a subset of brain barrier vessels that must be regenerating and of the kind that were temporarily fenestrated during fetal life. (C) 1996 Academic Press, Inc. RP Kaya, M (reprint author), NINCDS, NEUROBIOL LAB, NIH, BLDG 36, ROOM 2A-21, BETHESDA, MD 20892 USA. NR 31 TC 19 Z9 20 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD NOV PY 1996 VL 142 IS 1 BP 6 EP 13 DI 10.1006/exnr.1996.0174 PG 8 WC Neurosciences SC Neurosciences & Neurology GA VT664 UT WOS:A1996VT66400002 PM 8912894 ER PT J AU Chandrasekaran, K Hatanpaa, K Brady, DR Rapoport, SI AF Chandrasekaran, K Hatanpaa, K Brady, DR Rapoport, SI TI Evidence for physiological down-regulation of brain oxidative phosphorylation in Alzheimer's disease SO EXPERIMENTAL NEUROLOGY LA English DT Review ID GLUCOSE-TRANSPORTER GENE; LIVER MITOCHONDRIAL-DNA; OXIDASE COX ACTIVITY; CYTOCHROME-OXIDASE; MESSENGER-RNA; NEURONAL-ACTIVITY; CEREBRAL-CORTEX; ELECTRICAL-STIMULATION; FUNCTIONAL ALTERATIONS; DEGENERATIVE DISEASES AB In vivo imaging of patients with Alzheimer's disease using positron emission tomography (PET) demonstrates progressive reductions in brain glucose metabolism and blood flow in relation to dementia severity, more so in association than primary cortical regions, These reductions likely follow regional synaptic loss or dysfunction and reflect physiological down-regulation of gene expression for glucose delivery, oxidative phosphorylation (OXPHOS), and energy consumption in brain, Indeed, the pattern of down-regulation of expression for both mitochondrial and nuclear genes coding for subunits of OXPHOS enzymes in the Alzheimer brain resembles the pattern of down-regulation in normal brain caused by chronic sensory deprivation. In both cases, do cvn-regulation likely is mediated by changes in transcriptional and posttranscriptional regulatory factors, Physiological down-regulation of OXPHOS gene expression in Alzheimer's is consistent with PET evidence that cognitive or psychophysical activation of mildly to moderately demented Alzheimer's patients can augment brain-blood flow and glucose metabolism to the same extent as in control subjects, If the primary neuronal defect that leads to reduced brain energy demand in Alzheimer's disease could be prevented or treated, brain glucose transport and OXPHOS enzyme activities might recover to normal levels. (C) 1996 Academic Press, Inc. C1 NCI,NIH,NEUROSCI LAB,BETHESDA,MD 20892. NR 103 TC 71 Z9 71 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD NOV PY 1996 VL 142 IS 1 BP 80 EP 88 DI 10.1006/exnr.1996.0180 PG 9 WC Neurosciences SC Neurosciences & Neurology GA VT664 UT WOS:A1996VT66400008 PM 8912900 ER PT J AU Pollard, HB Kuijpers, GA Adeyemo, OM Youdim, MBH Goping, G AF Pollard, HB Kuijpers, GA Adeyemo, OM Youdim, MBH Goping, G TI The MPTP-induced parkinsonian syndrome in the goldfish is associated with major cell destruction in the forebrain and subtle changes in the optic tectum SO EXPERIMENTAL NEUROLOGY LA English DT Article ID DOPAMINERGIC-NEURONS; N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; HYDROXYLASE; BRAIN AB The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can induce a parkinsonian syndrome in humans and nonhuman primates, which is susceptible to treatment and prevention by drugs such as L-DOPA and L-deprenyl, Recently, we have reported that MPTP can also cause a parkinsonian syndrome in the common goldfish, which appears to faithfully mirror the neurochemical and behavioral aspects of the action of MPTP in the higher vertebrates. In addition, we recently identified the likely teleost equivalent of the substantia nigra in the goldfish forebrain, the ''nucleus pars medialis,'' on the basis of its destruction by MPTP and selective protection by the MAO-B blocker L-deprenyl. In the present work we substantiate this conclusion by examining tissue destruction in the goldfish forebrain at increasing MPTP concentrations, up to the the LD(50) Of 200 mg/kg, In addition, we show that at the highest MPTP dose subtle changes also occur with low frequency in nondopaminergic cells in the optic tectum, and in ependymal cells lining the midbrain ventricle, The effects on ependymal cells are similar to those previously noted in the forebrain. We conclude that the goldfish model continues to faithfully mimic the histologic pattern of parkinsonian tissue destruction engendered by MPTP in primate models. (C) 1996 Academic Press, Inc. RP Pollard, HB (reprint author), NIDDK,CELL BIOL & GENET LAB,NIH,BETHESDA,MD 20892, USA. NR 16 TC 18 Z9 19 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD NOV PY 1996 VL 142 IS 1 BP 170 EP 178 DI 10.1006/exnr.1996.0188 PG 9 WC Neurosciences SC Neurosciences & Neurology GA VT664 UT WOS:A1996VT66400016 PM 8912908 ER PT J AU Vawter, MP BasaricKeys, J Li, YH Lester, DS Lebovics, RS Lesch, KP Kulaga, H Freed, WJ Sunderland, T Wolozin, B AF Vawter, MP BasaricKeys, J Li, YH Lester, DS Lebovics, RS Lesch, KP Kulaga, H Freed, WJ Sunderland, T Wolozin, B TI Human olfactory neuroepithelial cells: Tyrosine phosphorylation and process extension are increased by the combination of IL-1 beta, IL-6, NGF, and bFGF SO EXPERIMENTAL NEUROLOGY LA English DT Article ID NERVE GROWTH-FACTOR; SIGNAL-TRANSDUCING RECEPTOR; TUMOR-NECROSIS-FACTOR; ALZHEIMERS-DISEASE; PC12 CELLS; NEUROTROPHIC FACTOR; AMINOPEPTIDASE-N; KINASE-ACTIVITY; IN-VITRO; SYMPATHOADRENAL PROGENITOR AB Olfactory neuroepithelial cells (ONC) grown from biopsies of human donors are a novel cell culture system that may facilitate studies into normal and disease-related human neurobiology. We further characterized the expression of cell surface markers and intermediate filaments, and responses to neurotrophic factors by ONC. ONC are positive for cell surface markers N-CAM, PSA-N-CAM, neutral endopeptidase, N-aminopeptidase, NGF low-affinity receptor homologue (CD40), and transferrin receptor by flow cytometry for the intermediate filament proteins peripherin, vimentin, and NF-H by immunocytochemistry. Responses to neurotrophic factors measured were process outgrowth, cytoskeletal protein expression, and protein phosphorylation. Process outgrowth was increased by interleukin-1 beta(164-171) (IL-1 beta) or by the combination of IL-1 beta, interleukin-6 (IL-6), nerve growth factor (NGF), and basic fibroblast growth factor (bFGF). This combination of IL-1 beta, IL-6, NGF, and bFGF (16NF) increased expression of two cytoskeletal proteins, NF-H protein and microtubule-associated protein tau. Application of the individual neurotrophic factors IL-1 beta, IL-6, NGF, and bFGF increased protein phosphorylation, while 16NF produced an immediate increase in tyrosine phosphorylation of several proteins (MW of 40-80, 120, 150, and 190 kDa). The 16NF combination appears to act through a tyrosine-kinase-mediated pathway to induce process extension and increase NF-H expression. The ONC culture has the potential to be further explored to examine the relationship among process outgrowth, protein phosphorylation, and synergy between neurotrophin and cytokine receptor systems. (C) 1996 Academic Press, Inc. C1 NIMH, SECT GERIATR PSYCHIAT, WASHINGTON, DC 20032 USA. NIMH, NEUROPSYCHIAT BRANCH, WASHINGTON, DC 20032 USA. UNIV WURZBURG, DEPT PSYCHIAT, D-8700 WURZBURG, GERMANY. US FDA, CDER, DIV RES & TESTING, LAUREL, MD 20708 USA. NIDCD, BETHESDA, MD 20892 USA. RP Vawter, MP (reprint author), NIMH, SECT PRECLIN NEUROSCI, WASHINGTON, DC 20032 USA. RI Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 77 TC 26 Z9 28 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 0014-4886 EI 1090-2430 J9 EXP NEUROL JI Exp. Neurol. PD NOV PY 1996 VL 142 IS 1 BP 179 EP 194 DI 10.1006/exnr.1996.0189 PG 16 WC Neurosciences SC Neurosciences & Neurology GA VT664 UT WOS:A1996VT66400017 PM 8912909 ER PT J AU SchartonKersten, T Caspar, P Sher, A Denkers, EY AF SchartonKersten, T Caspar, P Sher, A Denkers, EY TI Toxoplasma gondii: Evidence for interleukin-12-dependent and -independent pathways of interferon-gamma production induced by an attenuated parasite strain SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Toxoplasma gondii; IFN-gamma; ts-4; ASGM-1, asialo-GM-1; mab, monoclonal antibody; Natural killer; nitric oxide; peritoneal exudate cells; scid, severe combined immunodeficiency; soluble tachyzoite proteins ID IMMUNE-DEFICIENCY SYNDROME; NECROSIS-FACTOR-ALPHA; CD8+ LYMPHOCYTES-T; IFN-GAMMA; CEREBRAL TOXOPLASMOSIS; ACTIVATED MACROPHAGES; NITRIC-OXIDE; IN-VIVO; RESISTANCE; CELLS AB Evidence for interleukin-12-dependent and -independent pathways of interferon-gamma production induced by an attenuated parasite strain. Experimental Parasitology 84, 102-114. Immunity in mice infected with Toxoplasma gondii is dependent upon the ability to generate protective levels of the cytokine IFN-gamma. In this report, we present evidence that the attenuated vaccine strain, ts-4, induces the latter cytokine by both IL-12-dependent and -independent pathways. In contrast, strain ME49 appears to induce IFN-gamma wholly in dependence upon IL-12. Thus, 88% of wildtype C57BL/6 mice treated with anti-IL-12 mAb survive ts-4 infection, unlike similarly treated ME49-infected animals. Moreover, while anti-IL-12 treatment reduced early IFN-gamma and nitric oxide production to background levels in ts-4-infected scid animals, the same treatment in infected C57BL/6 mice had no effect on production of the latter mediators. In addition, we found that anti-IL-12 treatment induces 100% mortality in CD4(+)-deficient MHC class II knockout mice infected with ts-4. Finally, production of nitric oxide (a molecule implicated in parasite control) was abrogated in ts-4-infected scid mice following depletion of IFN-gamma producing NK cells. Together, our results suggest that ts-4 induces IL-12-dependent and -independent IFN-gamma production in normal mice, but ME49 induces the latter cytokine only in dependence upon IL-12. Our data, furthermore, implicate involvement of T cells in the IL-12-independent component of the IFN-gamma response. (C) 1996 Academic Press, Inc. C1 CORNELL UNIV,COLL VET MED,DEPT MICROBIOL & IMMUNOL,ITHACA,NY 14850. RP SchartonKersten, T (reprint author), NIAID,PARASIT DIS LAB,IMMUNOBIOL SECT,BETHESDA,MD 20892, USA. NR 39 TC 23 Z9 25 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 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD NOV PY 1996 VL 84 IS 2 BP 102 EP 114 DI 10.1006/expr.1996.0096 PG 13 WC Parasitology SC Parasitology GA VV584 UT WOS:A1996VV58400001 PM 8932760 ER PT J AU Doherty, TM Coffman, RL AF Doherty, TM Coffman, RL TI Leishmania major: Effect of infectious dose on T cell subset development in BALB/c mice SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE antigen dose; cytokine secretion; immunology; infectious dose interferon-gamma; interleukin-4; Leishmania major; leishmaniasis; LmAg (freeze-thawed Leishmania major antigen); lymphokines; mice, inbred BALB/C; mice, inbred C57BL; murine leishmaniasis; T cell subsets; Thl (T helper 1); Th2 (T helper 2) ID STIMULATORY FACTOR-I; CUTANEOUS LEISHMANIASIS; MURINE LEISHMANIASIS; MONOCLONAL-ANTIBODY; INTERFERON-GAMMA; TH2 CLONES; IMMUNOLOGICAL REGULATION; SUSCEPTIBLE BALB/C; MEDIATED-IMMUNITY; INTERLEUKIN-4 AB Leishmania major; the causative agent of cutaneous leishmaniasis in humans, causes either a local cutaneous lesion or a fatal, disseminated infection in different strains of mice. It has been well established that the BALB/c strain of mice is extremely susceptible to L. major infection, due to the preferential development of Th2 responses. It has also been shown, however, that these mice have the potential to develop protective Th1 responses under appropriate conditions. In this paper we confirm earlier reports that BALB/c mice are capable of developing immunity when challenged with low doses of L, major and show that this is dependent on the induction of a Thl response which can be manipulated with anti-cytokine antibodies in the same way as more conventional experimental infections. Moreover, our data indicate that the development of immunity or susceptibility to L, major in the BALB/c mouse may reflect factors specific to infection such as persistance of the pathogen, infection of APC, or relative cytokine levels rather than simple antigen load, a finding which may be of general significance in infectious disease. (C) 1996 Academic Press, Inc. C1 DNAX RES INST MOL & CELLULAR BIOL INC,DEPT IMMUNOL,PALO ALTO,CA 94304. RP Doherty, TM (reprint author), NIAID,IMMUNOBIOL SECT,PARASIT DIS LAB,NIH,BLDG 4,BETHESDA,MD 20892, USA. NR 39 TC 50 Z9 51 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 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD NOV PY 1996 VL 84 IS 2 BP 124 EP 135 DI 10.1006/expr.1996.0098 PG 12 WC Parasitology SC Parasitology GA VV584 UT WOS:A1996VV58400003 PM 8932762 ER PT J AU Mahanty, S Luke, HE Kumaraswami, V Narayanan, PR Vijayshekaran, V Nutman, TB AF Mahanty, S Luke, HE Kumaraswami, V Narayanan, PR Vijayshekaran, V Nutman, TB TI Stage-specific induction of cytokines regulates the immune response in lymphatic filariasis SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Wuchereria bancrofti; Brugia malayi; microfilariae; lymphatic filariasis; elephantiasis; human; cytokines; IL-10; Th1; Th2; stage-specific immunity; microfilarial antigens; adult male antigens ID PARASITE-SPECIFIC ANERGY; BRUGIA-MALAYI; INFECTIVE LARVAE; BANCROFTIAN FILARIASIS; BALB/C MICE; ANTIGENS; RESPONSIVENESS; ANTIBODY; INTERLEUKIN-10; ACQUISITION AB Parasite stage-specific T cell responses were studied in Indians with lymphatic filariasis manifesting as elephantiasis (CP, n = 11) and asymptomatic microfilaremia (MF, II = 8), using antigens derived from the microfilarial, adult male only, and mixed adult male and female worms. Proliferative responses to microfilarial and mixed (male-female adult worm) antigens in MF individuals were markedly impaired compared to corresponding responses in individuals with CP. In contrast, T cell proliferative responses to adult male-derived antigens were not statistically different between the two groups. Analysis of antigen driven cytokine secretion by peripheral blood mononuclear cells from MF and CP individuals revealed significantly lower IL-2 and IFN-gamma production by MF in response to microfilarial and mixed antigens (but not to adult male antigen) compared to CP individuals. No differences were observed between MF and CP in parasite antigen-driven IL-4 or IL-5 production. Spontaneous and parasite-specific IL-10 secretion was also measured to determine if cytokine cross-regulation of Th1 responses may be a mechanism underlying the observed Th1 suppression. Spontaneous and microfilarial antigen-driven IL-10 was found to be significantly higher in MF than in CP individuals. These data indicate that MF individuals exhibit preferentially impaired Th1-type responses to microfilarial antigens and that microfilarial-induced IL-10 may be critical in the downregulation of specific Th1 responses. (C) 1996 Academic Press, Inc. C1 NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. TB RES CTR,MADRAS 600013,TAMIL NADU,INDIA. MADRAS MED COLL & GOVT GEN HOSP,DEPT PHARMACOL,MADRAS 600003,TAMIL NADU,INDIA. OI Mahanty, Siddhartha/0000-0003-1068-0524 NR 30 TC 50 Z9 51 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 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD NOV PY 1996 VL 84 IS 2 BP 282 EP 290 DI 10.1006/expr.1996.0114 PG 9 WC Parasitology SC Parasitology GA VV584 UT WOS:A1996VV58400019 PM 8932778 ER PT J AU Thomas, AP Bird, GSJ Hajnoczky, G RobbGaspers, LD Putney, JW AF Thomas, AP Bird, GSJ Hajnoczky, G RobbGaspers, LD Putney, JW TI Spatial and temporal aspects of cellular calcium signaling SO FASEB JOURNAL LA English DT Article DE cytosolic calcium; calcium oscillations; calcium waves; inosital 1,4,5-trisphosphate ID PANCREATIC ACINAR-CELLS; CA2+-INDUCED CA2+ RELEASE; CYTOPLASMIC FREE CALCIUM; XENOPUS-LAEVIS OOCYTES; SINGLE-RAT HEPATOCYTES; ONE-POOL MODEL; INOSITOL TRISPHOSPHATE; INTRACELLULAR CALCIUM; CYTOSOLIC CALCIUM; FURA-2-LOADED HEPATOCYTES AB Cytosolic Ca2+ signals are often organized in complex temporal and spatial patterns, even under conditions of sustained stimulation. In this review we discuss the mechanisms and physiological significance of this behavior in nonexcitable cells, in which the primary mechanism of Ca2+ mobilization is through (1,4,5)IP3-dependent Ca2+ release from intracellular stores. Oscillations of cytosolic free Ca2+ ([Ca2+](i)) are a common form of temporal organization; in the spatial domain, these [Ca2+](i) oscillations may take the form of [Ca2+](i) waves that propagate throughout the cell or they may be restricted to specific subcellular regions. These patterns of Ca2+ signaling result from the limited range of cytoplasmic Ca2+ diffusion and the feedback regulation of the pathways responsible for Ca2+ mobilization. In addition, the spatial organization of [Ca2+](i) changes appears to depend on the strategic distribution of Ca2+ stores within the cell. One type of [Ca2+](i) oscillation is baseline spiking, in which discrete [Ca2+](i) spikes occur with a frequency, but not amplitude, that is determined by agonist dose. Most current evidence favors a model in which baseline [Ca2+](i) spiking results from the complex interplay between [Ca2+](i) and (1,4,5)IP3 in regulating the gating of (1,4,5)IP3-sensitive intracellular Ca2+ channels. Sinusoidal [Ca2+](i) oscillations represent a mechanistically distinct type of temporal organization, in which agonist dose regulates the amplitude but has no effect on oscillation frequency. Sinusoidal [Ca2+](i) oscillations can be explained by a negative feedback effect of protein kinase C on the generation of (1,4,5)IP3 at the level of phospholipase C or its activating G-protein. The physiological significance of [Ca2+](i) oscillations and waves is becoming more established with the observation of this behavior in intact tissues and by the recognition of Ca2+-dependent processes that are adapted to respond to frequency-modulated oscillatory [Ca2+](i) signals. In some cells, these [Ca2+](i) signals are targeted to control processes in limited cytoplasmic domains, and in other systems [Ca2+](i) waves can be propagated through gap junctions to coordinate the function of multicellular systems. C1 NIEHS,CELLULAR & MOL PHARMACOL LAB,NIH,RES TRIANGLE PK,NC 27709. RP Thomas, AP (reprint author), THOMAS JEFFERSON UNIV,DEPT PATHOL ANAT & CELL BIOL,271 JAH1020 LOCUST ST,PHILADELPHIA,PA 19107, USA. RI Thomas, Andrew/C-6755-2013 FU NIAAA NIH HHS [AA07215]; NIDA NIH HHS [DA06293]; NIDDK NIH HHS [DK38422] NR 94 TC 375 Z9 383 U1 2 U2 14 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 NOV PY 1996 VL 10 IS 13 BP 1505 EP 1517 PG 13 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA VU982 UT WOS:A1996VU98200007 PM 8940296 ER PT J AU George, JD Fail, PA Grizzle, TB Heindel, JJ AF George, JD Fail, PA Grizzle, TB Heindel, JJ TI Nitrofurazone: Reproductive assessment by continuous breeding in Swiss mice SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID DOSE LEVELS; TOXICITY; TESTIS; RATS AB Nitrofurazone (NTFZ), a nitrofuran antibiotic, was evaluated for reproductive toxicity in Swiss CD-1 mice using the Reproductive Assessment by Continuous Breeding protocol. Male and female mice were cohabited for 15 weeks and exposed to NTFZ in feed at concentrations of 0, 100, 375, and 750 ppm (14-102 mg/kg/day). F-0 750-ppm breeding pairs had significantly reduced fertility after 7 days of exposure to NTFZ (17% fertile compared to 98% for control pairs) and were infertile after the second litter. F-0 mid-dose pairs had progressively decreasing fertility (47% by the fifth litter), reduced litter size. and reduced proportion of pups born alive. Crossover breeding of control and high-dose F-0 animals confirmed infertility in high-dose males and reduced litter size and pup weight in high-dose females when compared to the control X control group. At necropsy, there were no effects on body weight, but F-0 males had reduced testis weight at the high dose and reduced epididymal sperm concentration and abnormal sperm morphology at all doses of NTFZ. Increased liver as well as kidney and adrenal weights (combined) were observed at 375 and 750 ppm; hepatic hypertrophy was noted microscopically at 750 ppm. F-0 females had reduced body weight, hepatic hypertrophy, and altered estrous cycles at 750 ppm and reduced ovarian weight at all doses. In the second generation, F-1 mice at 375 ppm had reduced postnatal survival and body weight and produced smaller F-2 litters compared to control mice. At necropsy, F-1 males had reduced testes weight and epididymal sperm concentration, abnormal sperm morphology, hepatic hypertrophy at 375 ppm, and borderline nephropathy at 100 and 375 ppm. F-1 females had decreased body, liver, and ovarian weight at 375 ppm and altered estrous cycles at 100 and 375 ppm. Thus, NTFZ at greater than or equal to 100 ppm (greater than or equal to 14 mg/kg/day) caused adverse reproductive effects in F-0 male and female and F-1 female mice in the presence of relatively mild systemic toxicity. (C) 1996 Society of Toxicology. C1 NIEHS, NATL TOXICOL PROGRAM, DEV & REPROD TOXICOL GRP, RES TRIANGLE PK, NC 27709 USA. RP George, JD (reprint author), RES TRIANGLE INST, CTR LIFE SCI & TOXICOL, LAB REPROD TOXICOL, CHEM & LIFE SCI DIV, POB 12194, RES TRIANGLE PK, NC 27709 USA. FU NIEHS NIH HHS [N01-ES-6-5141] NR 43 TC 4 Z9 6 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD NOV PY 1996 VL 34 IS 1 BP 56 EP 66 DI 10.1006/faat.1996.0175 PG 11 WC Toxicology SC Toxicology GA VV022 UT WOS:A1996VV02200007 PM 8937892 ER PT J AU Orner, GA Donohoe, RM Hendricks, JD Curtis, LR Williams, DE AF Orner, GA Donohoe, RM Hendricks, JD Curtis, LR Williams, DE TI Comparison of the enhancing effects of dehydroepiandrosterone with the structural analog 16 alpha-fluoro-5-androsten-17-one on aflatoxin B-1 hepatocarcinogenesis in rainbow trout SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID PROLIFERATOR-INDUCED HEPATOCARCINOGENESIS; HEPATIC PEROXISOME PROLIFERATION; AMMONIUM PERFLUOROOCTANOATE; RAT-LIVER; INDUCTION; MICE; ENZYMES; CELL; CARCINOGENESIS; CANCER AB Dehydroepiandrosterone (DHEA) is an adrenal steroid with chemoprotective effects against a wide variety of conditions including cancer, obesity, diabetes, and cardiovascular disease, However, DHEA is also a carcinogen in laboratory animals, possibly through its function as a precursor of sex steroids or peroxisome proliferation, The structural analog 16 alpha-fluoro-5-androsten-17-one (8354) has been reported to have enhanced chemopreventive activity without the steroid precursor and peroxisome proliferating effects of DHEA, This study compares DHEA and 8354 in rainbow trout, a species that is resistant to peroxisome proliferation but is highly susceptible to the carcinogenic and tumor enhancing effects of DHEA. Trout were exposed as fry to aflatoxin B-1 (AFB(1)) or given a sham exposure, then were fed diets containing 444 ppm DHEA or 8354 for 6 months. Postinitiation treatment with DHEA significantly increased liver tumor incidence, multiplicity, and size compared to initiated controls, The analog 8354 slightly increased tumor incidence (p = 0.06) but had no effect on multiplicity or size, Six percent of trout treated with DHEA alone developed tumors, whereas no tumors occurred in noninitiated trout fed control or 8354-containing diets, Serum levels of androstenedione were elevated by DHEA (48-fold) or 8354 (6-fold) treatment, Serum beta-estradiol titers were increased in DHEA- but not 8354-treated trout. Vitellogenin was induced significantly by either DHEA (434-fold) or 8354 (21-fold), Peroxisomal beta-oxidation was not increased by either compound and catalase activity was decreased in DHEA-treated animals, Both steroids were potent inhibitors in vitro of trout liver glucose-6-phosphate dehydrogenase with IC50s of 24 and 0.5 mu M for DHEA and 8354, respectively. This research suggests that in trout the tumor enhancing effects of DHEA may be due to its function as a sex steroid precursor and are unrelated to peroxisome proliferation. These carcinogenic properties are reduced in the analog 8354 which has been advocated as an alternative to DHEA for chemoprevention. (C) 1996 Society of Toxicology. C1 OREGON STATE UNIV,TOXICOL PROGRAM,CORVALLIS,OR 97331. OREGON STATE UNIV,NIEHS,MARINE FRESHWATER BIOMED SCI CTR,CORVALLIS,OR 97331. OREGON STATE UNIV,DEPT FOOD SCI & TECHNOL,CORVALLIS,OR 97331. OREGON STATE UNIV,DEPT FISHERIES & WILDLIFE,CORVALLIS,OR 97331. RI Orner, Gayle/F-6876-2013 OI Orner, Gayle/0000-0002-4812-5297 FU NIEHS NIH HHS [ES03850, ES04766, ES07612] NR 61 TC 12 Z9 12 U1 1 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD NOV PY 1996 VL 34 IS 1 BP 132 EP 140 DI 10.1006/faat.1996.0183 PG 9 WC Toxicology SC Toxicology GA VV022 UT WOS:A1996VV02200015 PM 8937900 ER PT J AU Schulberg, HC Magruder, KM deGruy, F AF Schulberg, HC Magruder, KM deGruy, F TI Major depression in primary medical care practice - Research trends and future priorities SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article ID RANDOMIZED CLINICAL-TRIALS; MENTAL-HEALTH-CARE; ANXIETY; OUTCOMES; RECOGNITION; PHYSICIANS; DISORDERS; DISABILITY; MANAGEMENT; GUIDELINES AB This paper reviews recent developments in assessing and treating major depression in primary care practice and proposes needed research directions for the coming years. Topics warranting attention include the predictive validity of psychiatric nomenclatures specific to general medical settings; the impact of patient, clinician, and system factors on the physician's assessment of major depression; the relationship between diagnostic and treatment decisions; and the course of this disorder when treated in primary care facilities by generalists or specialists. (C) 1996 Elsevier Science Inc. C1 UNIV PITTSBURGH,SCH MED,PITTSBURGH,PA. NIMH,ROCKVILLE,MD 20857. UNIV S ALABAMA MED,MOBILE,AL 36688. FU NIMH NIH HHS [MH45815] NR 90 TC 28 Z9 28 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV PY 1996 VL 18 IS 6 BP 395 EP 406 DI 10.1016/S0163-8343(96)00093-X PG 12 WC Psychiatry SC Psychiatry GA VT951 UT WOS:A1996VT95100002 PM 8937905 ER PT J AU Reynolds, PA Powlesland, RM Keen, TJ Inglehearn, CF Cunningham, AF Green, ED Brown, KW AF Reynolds, PA Powlesland, RM Keen, TJ Inglehearn, CF Cunningham, AF Green, ED Brown, KW TI Localization of a novel t(1;7) translocation associated with Wilms' tumor predisposition and skeletal abnormalities SO GENES CHROMOSOMES & CANCER LA English DT Article ID LOCUS; GENE; HETEROZYGOSITY; CHROMOSOME-11; CONSTRUCTION; FEATURES; CANCER; KIDNEY AB Cytogenetic analysis of predisposition syndromes has played a critical role in the elucidation of the genetics of Wilms' tumor (WT). Therefore, we became interested in a patient who presented with a WT and a nephrogenic rest in the contralateral kidney (suggestive of a predisposition) and a de novo t(1;7)(q42;p15) constitutional translocation as the only visible cytogenetic abnormality. He also had bilateral radial aplasia and other skeletal abnormalities, but there was no manifestation of any syndrome previously associated with WT. In the tumor, the translocation was retained, and the other 7p region was lost by the formation of an isochromosome i(7q). Here, we report the localization of the chromosome 7 breakpoint within a yeast artificial chromosome (YAC) contig by using fluorescence in situ hybridization (FISH), localizing the breakpoint between markers sWSS355 and sWSS1449. A number of YACs span the breakpoint and, thus, contain the region that is disrupted by the translocation. This may represent the site of a novel tumor suppressor gene that is involved in WT and also in normal renal development. (C) 1996 Wiley-Liss, Inc. C1 UCL, INST OPHTHALMOL, DEPT MOL GENET, LONDON, ENGLAND. NIH, NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. RP Reynolds, PA (reprint author), UNIV BRISTOL, SCH MED SCI, DEPT PATHOL & MICROBIOL, CLIC RES UNIT, BRISTOL BS8 1TD, AVON, ENGLAND. RI Brown, Keith/C-3355-2009 OI Brown, Keith/0000-0002-4258-5129 FU Wellcome Trust NR 32 TC 19 Z9 19 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD NOV PY 1996 VL 17 IS 3 BP 151 EP 155 DI 10.1002/(SICI)1098-2264(199611)17:3<151::AID-GCC2>3.0.CO;2-3 PG 5 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA VU933 UT WOS:A1996VU93300002 PM 8946193 ER PT J AU Therrien, M Michaud, NR Rubin, GM Morrison, DK AF Therrien, M Michaud, NR Rubin, GM Morrison, DK TI KSR modulates signal propagation within the MAPK cascade SO GENES & DEVELOPMENT LA English DT Article DE KSR; MAPK; MEK; Raf; Ras; signal transduction ID NUCLEOTIDE DISSOCIATION STIMULATOR; DEVELOPING DROSOPHILA EYE; XENOPUS-OOCYTES; PLASMA-MEMBRANE; TYROSINE KINASE; GENE ENCODES; C-ELEGANS; RAS; ACTIVATION; TRANSDUCTION AB Kinase suppressor of Ras (KSR) is a recently identified component of Ras-dependent signaling pathways. In this report, we show that murine KSR1 (mKSR1) cooperates with activated Ras to promote Xenopus oocyte maturation and cellular transformation and provide evidence that this cooperation occurs by accelerating mitogen and extracellular regulated kinase (MEK) and mitogen-activated protein kinase (MAPK) activation. We also find that mKSR1 associates with Raf-1 at the plasma membrane in a Ras-dependent manner, indicating the presence of a membrane-bound kinase signaling complex. Although mKSR1 is related structurally to Raf-1, our findings reveal striking functional differences between these proteins. In marked contrast to the isolated amino- and carboxy-terminal domains of Raf-1, the KSR amino terminus also cooperates with Ras, whereas the carboxy-terminal kinase domain blocks pas signaling as well as MEK and MAPK activation. The isolated KSR kinase domain suppressed Xenopus oocyte maturation, cellular transformation, and Drosophila eye development, suggesting that separation of the amino- and carboxy-terminal domains has uncoupled the normal regulation of KSR as a positive effector of Ras signaling. Together, our findings indicate that mKSR1 is an integral component of the MAPK module functioning via a novel mechanism to modulate signal propagation between Raf-1, MEK1, and MAPK. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOL BASIS CARCINOGENESIS LAB,FREDERICK,MD 21702. RP Therrien, M (reprint author), UNIV CALIF BERKELEY,HOWARD HUGHES MED INST,DEPT MOL & CELL BIOL,BERKELEY,CA 94720, USA. RI Tang, Amy/L-3226-2016; OI Tang, Amy/0000-0002-5772-2878; Rubin, Gerald/0000-0001-8762-8703 NR 35 TC 190 Z9 191 U1 2 U2 5 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 NOV 1 PY 1996 VL 10 IS 21 BP 2684 EP 2695 DI 10.1101/gad.10.21.2684 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA VT693 UT WOS:A1996VT69300002 PM 8946910 ER PT J AU Johnson, MR Polymeropoulos, MH Vos, HL deLuna, RIO Francomano, CA AF Johnson, MR Polymeropoulos, MH Vos, HL deLuna, RIO Francomano, CA TI A nonsense mutation in the cathepsin K gene observed in a family with pycnodysostosis SO GENOME RESEARCH LA English DT Article ID BONE-RESORPTION; MOLECULAR-CLONING; CYSTEINE PROTEINASES; OSTEOCLASTOMAS; ORGANIZATION; INHIBITION AB Pycnodysostosis (MIM 265800) is a rare, autosomal recessive skeletal dysplasia characterized by short stature, wide cranial sutures, and increased bone density and fragility. Linkage analysis localized the disease gene to human chromosome 1q21, and subsequently the genetic interval was narrowed to between markers D1S2612 and D1S2345. Expressed sequence tagged markers corresponding to cathepsin K, a cysteine protease highly expressed in osteoclasts and thought to be important in bone resorption, were mapped previously in the candidate region. We have identified a cytosine to thymidine transition at nucleotide 862 (GenBank accession no. S79895) of the cathepsin K coding sequence in the DNA of an affected individual from a large, consanguinous Mexican family. This mutation results in all arginine to STOP alteration at amino acid 241, predicting premature termination of cathepsin K mRNA translation. All affected individuals in this Family were homozygous for the mutation, suggesting that this alteration may lead to pycnodysostosis. Recognition of the role of cathepsin K in the etiology of pycnodysostosis should provide insights into the pathogenesis and treatment of other disorders of bone remodeling, including osteoporosis. C1 NIH,NATL CTR HUMAN GENOME RES,MED GENET BRANCH,BETHESDA,MD 20892. NIH,NATL CTR HUMAN GENOME RES,LAB GENET DIS RES,BETHESDA,MD 20892. NETHERLANDS CANC INST,AMSTERDAM,NETHERLANDS. HOSP INFANTIL MEXICO DR FEDERICO GOMEZ,MEXICO CITY,DF,MEXICO. NR 26 TC 91 Z9 92 U1 0 U2 0 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 NOV PY 1996 VL 6 IS 11 BP 1050 EP 1055 DI 10.1101/gr.6.11.1050 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA VV874 UT WOS:A1996VV87400002 PM 8938428 ER PT J AU Fernandez, MP Jenkins, NA Gilbert, DJ Copeland, NG Morgan, RO AF Fernandez, MP Jenkins, NA Gilbert, DJ Copeland, NG Morgan, RO TI Sequence and chromosomal localization of mouse annexin XI SO GENOMICS LA English DT Article ID NUCLEAR-LOCALIZATION; CRYSTAL-STRUCTURE; DNA-REPLICATION; LINKAGE MAP; GENE; SYNEXIN; PROTEIN; GENOME; VII; IDENTIFICATION AB Mouse annexin XI (anx11)(2) was cloned from a macrophage cDNA library and characterized by genetic linkage mapping, DNA sequencing, and structural comparison with other annexins. The Anx11 gene localized to mouse chromosome 14 in close linkage with the Rarb, Plau, and Wnt5a genes near the centromere and 1.8 cM distal from the Anx7 gene, The open reading frame was flanked by long, untranslated regions and encoded a 503-amino-acid protein with 93.1% identity to its human orthologue. Its 189-aa amino terminus corresponded to the widely expressed variant 1 of two possible, alternatively spliced forms. A previously described peptide from Aplysia brasiliana was identified as a closely related invertebrate homologue. Since annexin XI is known to be localized in the nucleus at certain stages of development, the identification of a region in tetrad repeats 3 and 4 resembling the ''chromo box'' domain may be relevant to a nuclear regulatory function of annexin XI. Knowledge of the mouse cDNA sequence and genetic map location will assist in the analysis of genomic organization and expression and provide a useful animal model to investigate gene function and hereditary phenotype for annexin XI. (C) 1996 Academic Press, Inc. C1 NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, MAMMALIAN GENET LAB, FREDERICK, MD 21702 USA. RP UNIV OVIEDO, FAC MED, DEPT BIOCHEM & MOL BIOL, E-33006 OVIEDO, SPAIN. OI Fernandez-Fernandez, Maria Pilar/0000-0001-6552-409X NR 39 TC 12 Z9 13 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 EI 1089-8646 J9 GENOMICS JI Genomics PD NOV 1 PY 1996 VL 37 IS 3 BP 366 EP 374 DI 10.1006/geno.1996.0571 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VU075 UT WOS:A1996VU07500012 PM 8938449 ER PT J AU Zha, HB Remmers, EF Szpirer, C Szpirer, J Zhang, HY Kozak, CA Wilder, RL AF Zha, HB Remmers, EF Szpirer, C Szpirer, J Zhang, HY Kozak, CA Wilder, RL TI The epimorphin gene is highly conserved among humans, mice, and rats and maps to human chromosome 7, mouse chromosome 5, and rat chromosome 12 SO GENOMICS LA English DT Article ID HYBRIDIZATION AB A genomic DNA fragment containing the rat epimorphin gene sequence was cloned from a rat DNA cosmid library using a mouse epimorphin cDNA probe. Within the cosmid insert, nine epimorphin exons were identified and sequenced. The predicted amino acid sequence of the rat epimorphin protein exhibited 96 and 86% identity with the mouse and human epimorphin proteins, respectively. Consistent with the developmentally related expression pattern of the mouse epimorphin gene, transcripts of the rat epimorphin gene were detected in 17-day postfertilization rat embryos. The gene, designated Epim, was assigned to rat chromosome 12 by somatic cell hybrid analysis and localized to 12q16 by fluorescence in situ hybridization. The mouse and human homologs of this gene were localized on mouse chromosome 5 and human chromosome 7 by linkage analysis and chromosomal in situ hybridization, respectively. (C) 1996 Academic Press, Inc. C1 NIAMSD,ARTHRIT & RHEUMATISM BRANCH,NIH,BETHESDA,MD 20892. FREE UNIV BRUSSELS,DEPT BIOL MOL,B-1640 RHODE ST GENESE,BELGIUM. NIAID,MOL MICROBIOL LAB,BETHESDA,MD 20892. NR 12 TC 5 Z9 7 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 NOV 1 PY 1996 VL 37 IS 3 BP 386 EP 389 DI 10.1006/geno.1996.0574 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VU075 UT WOS:A1996VU07500015 PM 8938452 ER PT J AU Kobayashi, T Inoue, I Jenkins, NA Gilbert, DJ Copeland, NG Watanabe, T AF Kobayashi, T Inoue, I Jenkins, NA Gilbert, DJ Copeland, NG Watanabe, T TI Cloning, RNA expression and chromosomal location of a mouse histamine H2 receptor gene SO GENOMICS LA English DT Article ID BETA-ADRENERGIC-RECEPTOR; MOLECULAR-CLONING; HISTAMINE-H2-RECEPTOR; TISSUES; BRAIN AB A mouse histamine H2 receptor (H2R) gene was isolated from a mouse ES cell genomic DNA library. The gene encoded a 358-amino-acid protein and displayed a 95% homology with the rat histamine H2 receptor at the amino acid level. It had features characteristic of other G-protein-coupled receptors. Reverse transcriptase-polymerase chain reaction analysis of total RNA prepared from mouse tissues showed that the gene was highly expressed in stomach and moderately in brain and heart. A weak expression was also detected in liver. An interspecific backcross analysis revealed that the mouse H2R gene, designated Hrh2, was located in the central region of chromosome 13. (C) 1996 Academic Press, Inc. C1 KYUSHU UNIV,MED INST BIOREGULAT,DEPT MOL IMMUNOL,HIGASHI KU,FUKUOKA 81282,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. NR 18 TC 21 Z9 24 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 1 PY 1996 VL 37 IS 3 BP 390 EP 394 DI 10.1006/geno.1996.0575 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VU075 UT WOS:A1996VU07500016 PM 8938453 ER PT J AU Spangler, EL Ingram, DK AF Spangler, EL Ingram, DK TI Utilization of the rat as a model of mammalian aging: Impact of pathology on behavior SO GERONTOLOGY LA English DT Review DE morbidity; learning; hematology; rodent ID MALE F344 RATS; ANIMAL-MODELS; DIETARY RESTRICTION; LEARNING-PERFORMANCE; FISCHER-344 RATS; RODENT MODELS; MAZE; GERONTOLOGY; IMPAIRMENT; LEUKEMIA AB Because pathology is concomitant to aging in rat strains, extraneous variance can be added to studies of aging at all levels of analysis. Thus, several gerontologists have made recent requests for characterization of pathology in aging studies including not only investigators' reports of diseases commonly observed (e.g., Sendai virus) and the occurrence of prevalent age-related lesions (e.g., nephropathy, leukemia, radiculoneuropathy) in rodent colonies, but also how specific disease processes might impact on the variable of interest in their investigation. Reported here are simple techniques (e.g., physical examination, necropsy to identify lesions, hematocrit, Wright stain) used routinely by our laboratory to screen for the presence of age-related disease in studies using Fischer 344 and Wistar rats. Routine health screening by physical examination and blood testing in our studies has allowed us either to eliminate moribund rats or to assess whether deficient performance was related to health status when these animals had been included in behavioral investigations. Additional health screens (e.g., antibodies for specific tumors) need to be developed. Investigators should be encouraged to utilize existing techniques, such as those reported here, and new technologies either to screen moribund animals from studies or to demonstrate that the pathology observed does or does not impact on the variable under investigation. RP Spangler, EL (reprint author), NIA, GERONTOL RES CTR, NATHAN W SHOCK LABS, MOL PHYSIOL & GENET SECT, JOHNS HOPKINS BAYVIEW MED CTR, BALTIMORE, MD 21224 USA. NR 38 TC 5 Z9 5 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0304-324X J9 GERONTOLOGY JI Gerontology PD NOV-DEC PY 1996 VL 42 IS 6 BP 301 EP 311 PG 11 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA VR194 UT WOS:A1996VR19400001 PM 8930617 ER PT J AU Sun, YP Hildesheim, A Brinton, LA Nasca, PC Trimble, CL Kurman, RJ Viscidi, RP Shah, KV AF Sun, YP Hildesheim, A Brinton, LA Nasca, PC Trimble, CL Kurman, RJ Viscidi, RP Shah, KV TI Human papillomavirus-specific serologic response in vulvar neoplasia SO GYNECOLOGIC ONCOLOGY LA English DT Article ID INVASIVE CERVICAL-CANCER; SQUAMOUS-CELL CARCINOMA; INTRAEPITHELIAL NEOPLASIA; WOMEN; ETIOLOGY; COLOMBIA; TYPE-16; SPAIN AB Epidemiological and virological evidence suggests that invasive squamous cell carcinoma (SCC) of the vulva is etiologically heterogeneous and that basaloid or warty SCC (BWSCC) and vulvar intraepithelial neoplasia (VIN) are linked to human papillomavirus (HPV) infections while keratinizing SCC (KSCC) is a non-HPV-associated malignancy, In the present study, HPV-specific antibodies in sera of patients with BWSCC, VIN, and KSCC and of controls were examined by ELISA for antibodies reactive to HPV-16 virus-like particles (VLP) and in radioimmunoprecipitation assays for antibodies to HPV-16 E6 and E7 proteins expressed by in vitro transcription and translation, The prevalences of antibodies to HPV-16 VLPs were significantly higher in HPV-associated VIN (59.1%) and BWSCC (50.0%) than in KSCC (22.2%) and controls (18.2%), Antibodies to E6 and E7 proteins were more prevalent in BWSCC than in any other groups, Prevalence of serum antibodies to any one of the antigen preparations was significantly higher in BWSCC (64.3%) and VIN (59.1%) than in KSCC (27.8%) and controls (22.2%), Also, sera with high antibody titers were found more frequently in BWSCC and VIN cases than in controls, These data provide immunological evidence in support of the observation that VIN and BWSCC, but not KSCC, are associated with HPV infections. (C) 1996 Academic Press, Inc. C1 JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. UNIV MASSACHUSETTS,SCH PUBL HLTH & HLTH SCI,AMHERST,MA 01003. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU NCI NIH HHS [CA56514, CA57550] NR 16 TC 15 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD NOV PY 1996 VL 63 IS 2 BP 200 EP 203 DI 10.1006/gyno.1996.0306 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA VT121 UT WOS:A1996VT12100008 PM 8910627 ER PT J AU Scully, RE Henson, DE Nielsen, ML Ruby, SG AF Scully, RE Henson, DE Nielsen, ML Ruby, SG TI Practice protocol for the examination of specimens removed from patients with ovarian tumors: A basis for checklists (Reprinted from Arch Pathol Lab Med, vol 119, pg 1012-1022, 1995) SO GYNECOLOGIC ONCOLOGY LA English DT Reprint ID PROGNOSTIC-SIGNIFICANCE; CELL TUMORS; CARCINOMA; CANCER; BORDERLINE; STAGE C1 NCI,EARLY DETECT BRANCH,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. HINSDALE HOSP,DEPT LAB MED & PATHOL,HINSDALE,IL. NR 42 TC 4 Z9 4 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD NOV PY 1996 VL 63 IS 2 BP 276 EP 289 DI 10.1006/gyno.1996.0320 PG 14 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA VT121 UT WOS:A1996VT12100022 PM 8910641 ER PT J AU Likhtarev, IA Kovgan, LN Vavilov, SE Gluvchinsky, RR Perevoznikov, ON Litvinets, LN Anspaugh, LR Kercher, JR Bouville, A AF Likhtarev, IA Kovgan, LN Vavilov, SE Gluvchinsky, RR Perevoznikov, ON Litvinets, LN Anspaugh, LR Kercher, JR Bouville, A TI Predictive and retrospective dose assessment - Response SO HEALTH PHYSICS LA English DT Letter C1 LAWRENCE LIVERMORE NATL LAB, DOSE RECONSTRUCT PROGRAM, LIVERMORE, CA 94550 USA. NCI, BETHESDA, MD 20892 USA. RP Likhtarev, IA (reprint author), UKRAINE ACAD TECHNOL SCI, UKRAINIAN RADIAT PROTECT INST, UA-252050 KIEV, UKRAINE. NR 17 TC 0 Z9 0 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 NOV PY 1996 VL 71 IS 5 BP 798 EP 799 PG 2 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 VM896 UT WOS:A1996VM89600033 ER PT J AU Xu, GW Sun, ZT Forrester, K Wang, XW Coursen, J Harris, CC AF Xu, GW Sun, ZT Forrester, K Wang, XW Coursen, J Harris, CC TI Tissue-specific growth suppression and chemosensitivity promotion in human hepatocellular carcinoma cells by retroviral-mediated transfer of the wild-type p53 gene SO HEPATOLOGY LA English DT Article ID ALPHA-FETOPROTEIN GENE; CANCER CELLS; RECOMBINANT ADENOVIRUS; HUMAN LIVER; IN-VIVO; EXPRESSION; THERAPY; MUTATIONS; APOPTOSIS; REGION AB Selective expression of cytotoxic gene products in tumor cells is one of the goals of gene therapy for treating cancer. We are developing such a strategy for the treatment of human hepatocellular carcinoma (HCC) by linking the wild-type p53 (WT-p53) gene with HCC-associated transcriptional control elements (TCE) to achieve selective growth inhibition of retrovirally transduced HCC cells. Replication defective, amphotrophic retroviruses were constructed containing a WT-p53 complementary DNA (cDNA) that is transcriptionally regulated by the HCC-associated a-fetoprotein (AFP) gene TCE. Expression of exogenous WT-p53 from this retroviral vector was limited to AFP-producing cells. Introduction of WT-p53 into AFP-positive HCC cells by retroviral infection markedly inhibited their clonal growth in monolayer and soft agar cultures, and increased the sensitivity of these cells to the chemotherapeutic drug, cisplatin. Therefore, restoration of WT-p53 expression in HCC cells, in combination with chemotherapeutic drugs, can be considered as a strategy for the therapy of human liver cancer. C1 CAMS,LAB MOL IMMUNOL,INST CANC,BEIJING,PEOPLES R CHINA. RP Xu, GW (reprint author), NCI,HUMAN CARCINOGENESIS LAB,DIV BASIC SCI,NIH,BLDG 37,ROOM 2C01,BETHESDA,MD 20892, USA. RI Wang, Xin/B-6162-2009 NR 30 TC 59 Z9 71 U1 1 U2 1 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 NOV PY 1996 VL 24 IS 5 BP 1264 EP 1268 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VQ934 UT WOS:A1996VQ93400046 PM 8903408 ER PT J AU Zhao, ZX Ashery, RS Wild, JL Young, PL AF Zhao, ZX Ashery, RS Wild, JL Young, PL TI Demographic and behavioral characteristics of Hispanic female sexual partners of injection drug users SO HISPANIC JOURNAL OF BEHAVIORAL SCIENCES LA English DT Article ID HIV INFECTION; WOMEN; AIDS AB This is a study of baseline demographic, drug, and sex risk behavior data collected on 1,370 Hispanic female sexual partners of injection drug users (IDUs) located in San Juan, Puerto Rico (n = 618), Juarez Mexico (n = 600), and the continental United States (n = 152). The study found significant differences in the demographics within the three sites in terms of age, marital status, education, employment, and income source. Differences were also found in past history of drug use, past history of sexual risk behaviors, current drug use, and current sexual risk behaviors. Only 8.5% of the women in the study had used a condom within the last SO days prior to study entrance. Over half had been sexually abused during adulthood The study found a need for site-specific AIDS prevention interventions based on the demographics and risk behaviors within specific groups of female sexual partners of IDUs. The study also demonstrates a need to address the issues of sexual and physical abuse for these women. C1 NIDA,PREVENT RES BRANCH,NIH,LEXINGTON,KY 40583. NR 14 TC 0 Z9 0 U1 0 U2 1 PU SAGE SCIENCE PRESS PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0739-9863 J9 HISPANIC J BEHAV SCI JI Hisp. J. Behav. Sci. PD NOV PY 1996 VL 18 IS 4 BP 550 EP 562 DI 10.1177/07399863960184008 PG 13 WC Psychology, Multidisciplinary SC Psychology GA VR211 UT WOS:A1996VR21100008 ER PT J AU Hunyady, B Mezey, E Pacak, K Palkovits, M AF Hunyady, B Mezey, E Pacak, K Palkovits, M TI Identification of endogenous peroxidase-containing cells as eosinophils in the gastrointestinal system SO HISTOCHEMISTRY AND CELL BIOLOGY LA English DT Article ID IMMUNOPEROXIDASE PROCEDURES; HORSERADISH-PEROXIDASE; MONOCLONAL-ANTIBODIES; REFLUX ESOPHAGITIS; INHIBITION; IMMUNOHISTOCHEMISTRY; GASTROENTERITIS; VISUALIZATION; METHANOL; PROTEIN AB Endogenous peroxidase (EPX) activity in certain cells in the gastrointestinal system interferes with immunohistochemical methods based on the horseradish peroxidase-catalyzed substrate deposition. We studied the distribution and characteristics of these cells. We also report an effective and antigen-preserving EPX blocking method, to make possible the evaluation of immunoperoxidase stainings in cryostat sections. The EPX-containing cells (EPX cells) are present in every part of the gastrointestinal tract, predominantly in the tunica propria. We identified them as eosinophil cells in May-Grunwald-Giemsa stained sections. The complete match was confirmed by different fluorescence techniques. Firstly, the EPX cells were labeled by a red fluorochrome-conjugated substrate of peroxidase enzymes, rhodamine-tyramide, whereas the eosinophil cells were labeled by the green fluorochrome, 1-hydroxy-3,6,8-pyrenetrisulfonic acid, which is known to label exclusively eosinophilic granules at pH 10. Secondly, all the EPX cells reacted with a monoclonal antibody against the eosinophil peroxidase enzyme. Finally, a set of commercially available leukocyte markers was used to characterize the EPX cells colabeled by fluorochrome-tyramides. Neither macrophages nor mast cells showed EPX activity. Increased numbers and altered distribution were seen in stressed rats and in ulcerated human stomach. C1 NINCDS,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. MED UNIV PECS,DEPT MED 1,H-7643 PECS,HUNGARY. RP Hunyady, B (reprint author), NIMH,CELL BIOL LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 36 TC 13 Z9 13 U1 0 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0301-5564 J9 HISTOCHEM CELL BIOL JI Histochem. Cell Biol. PD NOV PY 1996 VL 106 IS 5 BP 447 EP 456 DI 10.1007/s004180050063 PG 10 WC Cell Biology; Microscopy SC Cell Biology; Microscopy GA VR843 UT WOS:A1996VR84300001 PM 8950602 ER PT J AU Flemming, P Grothe, W Maschek, H Petry, KU Wellmann, A Georgii, A AF Flemming, P Grothe, W Maschek, H Petry, KU Wellmann, A Georgii, A TI The site of inhibin production in ovarian neoplasms SO HISTOPATHOLOGY LA English DT Article DE inhibin; ovarian neoplasms; sex-cord-stromal tumours ID GRANULOSA-CELL TUMORS; POSTMENOPAUSAL WOMEN; IMMUNOREACTIVE INHIBIN; DIMERIC INHIBIN; MARKER AB Inhibin, a physiological product of ovarian follicle cells, normally absent in serum of postmenopausal women, is elevated in adult granulosa cell tumours of the ovary, Recently, high serum levels of inhibin were reported in carcinomas and, surprisingly, also in Krukenberg tumours of the ovary, This study attempted to determine the site of inhibin production in primary (111 cases), metastatic (13) and secondary (10) ovarian tumours by using immunohistochemistry. Positive staining in tumour cells was encountered in all cases of sex-cord- stromal cell rumours, adult (13) and juvenile (3) granulosa cell tumours, thecofibromas (10), in a lipid cell tumour (1) and a Sertoli-Leydig cell tumour (1). Primary and secondary tumours not derived from sex-cord stroma revealed no positivity in tumour cells, but in theca-like cells in the surrounding non-neoplastic ovarian stroma, A positive reaction was not observed in non-tumour-bearing ovaries of a control group. The ovarian inhibin of postmenopausal women is derived from activated sex-cord stroma or sex-cord-stromal neoplasms. Therefore, elevated serum inhibin concentrations in women with primary or secondary ovarian neoplasms with other histogenesis seem to be due to an activation of the non-neoplastic ovarian stroma, Inhibin will fail to be a tumour marker in these cases. By contrast, it will be useful in proving sex-cord differentiation by immunohistochemistry and might be used in surveillance of malignant sex-cord derived neoplasms by serum assays. C1 HANNOVER MED SCH,INST PATHOL,D-30625 HANNOVER,GERMANY. HANNOVER MED SCH,FRAUENKLIN,D-30625 HANNOVER,GERMANY. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NR 17 TC 54 Z9 54 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD NOV PY 1996 VL 29 IS 5 BP 465 EP 468 DI 10.1046/j.1365-2559.1996.d01-511.x PG 4 WC Cell Biology; Pathology SC Cell Biology; Pathology GA VU344 UT WOS:A1996VU34400010 PM 8951493 ER PT J AU Ide, SE DeLuna, RIO Francomano, CA Polymeropoulos, MH AF Ide, SE DeLuna, RIO Francomano, CA Polymeropoulos, MH TI Exclusion of the MSX1 homeobox gene as the gene for the Ellis van Creveld syndrome in the Amish SO HUMAN GENETICS LA English DT Article ID EXPRESSION; HOX-7; HOMEODOMAIN; SEQUENCE AB Ellis van Creveld syndrome (EVC) is an autosomal recessive disorder which has previously been mapped to human chromosome 4p16.1. This disorder is characterized by disproportionate dwarfism, polydactyly, cleft palate, natal teeth, and congenital heart disease. The MSX1 homeobox gene also maps to the 4p16.1 region. Msx gene transcripts in the mouse embryo are known to be involved in pattern formation of the developing limb bud and craniofacial bones. Thus, on the basis of both map location and known gene function, MSX1 was an excellent candidate as the causative gene for EVC. Nonetheless, direct DNA sequencing of both exons of the MSX1 gene in five affected individuals segregating with the EVC phenotype, as well as those of two obligate carriers, revealed no mutations in the coding region of the gene. C1 NIH,NATL CTR HUMAN GENOME RES,LAB GENET DIS RES,GENE MAPPING UNIT,BETHESDA,MD 20892. NIH,NATL CTR HUMAN GENOME RES,MED GENET BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,CTR MED GENET,PHILADELPHIA,PA. NR 19 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD NOV PY 1996 VL 98 IS 5 BP 572 EP 575 DI 10.1007/s004390050261 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA VM743 UT WOS:A1996VM74300012 PM 8882877 ER PT J AU Fischer, U Meltzer, P Meese, E AF Fischer, U Meltzer, P Meese, E TI Twelve amplified and expressed genes localized in a single domain in glioma SO HUMAN GENETICS LA English DT Article ID HUMAN-MALIGNANT GLIOMAS; HUMAN SARCOMAS; CHROMOSOME MICRODISSECTION; AMPLIFICATION; MDM2; REGION; PROTEIN; CELLS; CDNAS; CDK4 AB Gene amplification has been associated both with tumor stage and progression in human gliomas. Several distinct amplified loci have been identified by comparative genomic hybridization and Southern blot analysis. It has been increasingly recognized that amplified domains comprise multiple genes. Here, we demonstrate amplification of up to 12 different genes from an amplified domain at 12q13-15 that has been found in approximately 15% of astrocytomas and glioblastomas. The amplified genes were GLI, WNT1, MDM2, SAS, CDK4, OS-4, GAS16, GAS27, GAS41, GAS56, GAS 64 and GAS89. In one glioblastoma all 12 amplified genes were also found to be expressed. These results strongly warrant the search for as yet unidentified genes in regions previously reported to be amplified. C1 UNIV SAAR HOSP,SCH MED,DEPT HUMAN GENET,D-66421 HOMBURG,GERMANY. NATL CTR HUMAN GENOME RES,CANC GENET LAB,NIH,BETHESDA,MD 20892. NR 21 TC 49 Z9 50 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD NOV PY 1996 VL 98 IS 5 BP 625 EP 628 DI 10.1007/s004390050271 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA VM743 UT WOS:A1996VM74300022 PM 8882887 ER PT J AU Schoedel, KE Greco, MA StetlerStevenson, WG Ohori, NP Goswami, S Present, D Steiner, GC AF Schoedel, KE Greco, MA StetlerStevenson, WG Ohori, NP Goswami, S Present, D Steiner, GC TI Expression of metalloproteinases and tissue inhibitors of metalloproteinases in giant cell tumor of bone: An immunohistochemical study with clinical correlation SO HUMAN PATHOLOGY LA English DT Article DE giant cell tumor; metalloproteinases; tissue inhibitors of metalloproteinases; bone tumor; immunohistochemistry; pathology ID MATRIX METALLOPROTEINASE-2; INTERSTITIAL COLLAGENASE; METASTASIS; INVASION; STROMELYSIN; OSTEOCLASTS AB The clinical behavior of giant cell tumors (GCTs) is unpredictable. To gain insight into this tumor's biological behavior, matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) were studied. These substances play essential roles in wound healing and neoplastic invasion and metastasis. Paraffin-embedded, tissue iras collected from 18 cases of histologically benign GCT, with 17 treated by curettage and 1 by resection. Eight cases showed no recurrence after a minimum of 2.5 years, and 10 had. local recurrence. One showed metastasis. Antibodies to MMP-9, MMP-2, TIMP-1, and TIMP-2 were applied by immunohistochemical methods. In all cases, MMP-9 nas strongly expressed in giant cells predominantly in a diffuse pattern and was strong but focal in stromal cells. MMP-2 decorated stromal cells and giant cells heterogeneously. TIMP-1 was variably expressed in giant cells of the nonrecurrent cases and was strongly present in a diffuse or patchy distribution in the stromal cells in 6 of 8 cases. However, in 9 of 10 recurrent cases, TIMP-1 was expressed weakly by both giant and stromal cells. TIMP-2 was variably expressed in the giant cells of the nonrecurrent cases, but 6 of 8 nonrecurrent cases showed strong stromal cell positivity For TIMP-2. Weak staining for TIMP-2 was observed in 7 of 10 recurrent cases in the stromal cells and 9 of 10 recurrent cases in the giant cells. These results indicate that expression of MMPs and TIMPs differs in plant cells and stromal cells in the same tumor. More significantly, in contrast to the nonrecurrent giant cell tumors, there is an imbalance in the MMPs and TIMPs in the recurrent tumors with a net excess of MMPs. This unopposed expression of MMPs in GCTs may play a role in breakdown of extracellular matrix and tissue invasion. Finally, these markers may prove useful in predicting behavior in these tumors. Copyright (C) 1996 by W.B. Saunders Company C1 HOSP JOINT DIS & MED CTR, DEPT PATHOL, NEW YORK, NY 10003 USA. NYU, BELLEVUE HOSP, MED CTR, NEW YORK, NY USA. NYU, KAPLAN COMPREHENS CANC CTR, NEW YORK, NY USA. NCI, BETHESDA, MD 20892 USA. UNIV PITTSBURGH, PITTSBURGH, PA USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 21 TC 17 Z9 19 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD NOV PY 1996 VL 27 IS 11 BP 1144 EP 1148 DI 10.1016/S0046-8177(96)90306-8 PG 5 WC Pathology SC Pathology GA VT123 UT WOS:A1996VT12300006 PM 8912822 ER PT J AU VandenBrule, FA Buicu, C Berchuck, A Bast, RC Deprez, M Liu, FT Cooper, DNW Pieters, C Sobel, ME Castronovo, V AF VandenBrule, FA Buicu, C Berchuck, A Bast, RC Deprez, M Liu, FT Cooper, DNW Pieters, C Sobel, ME Castronovo, V TI Expression of the 67-kD laminin receptor, galectin-1, and galectin-3 in advanced human uterine adenocarcinoma SO HUMAN PATHOLOGY LA English DT Article DE uterine adenocarcinoma; laminin-binding proteins; galectins; expression; invasion ID CARBOHYDRATE-BINDING PROTEIN-35; BREAST-CARCINOMA PROGRESSION; HUMAN-MELANOMA CELLS; MESSENGER-RNA; TUMOR INVASION; HUMAN COLON; MONOCLONAL-ANTIBODIES; EXTRACELLULAR-MATRIX; SURFACE EXPRESSION; CANCER CELLS AB Alterations of tumor cell interactions with laminin, a basement membrane glycoprotein, are consistent features of the invasive and metastatic phenotype. Qualitative and quantitative changes in the expression of cell surface laminin-binding proteins have been correlated with the ability of cancer cells to cross basement membranes during the metastatic cascade. Such phenotypic modifications are usually associated with poor prognosis. In this study, the authors examined the possibility that expression of three laminin-binding proteins, the 67-kD laminin receptor (67LR), galectin-1, and galectin-3, is altered in human endometrial cancer in a fashion similar to that reported in other carcinomas, such as breast, colon, and ovarian cancer. Twenty advanced uterine adenocarcinomas were analyzed for expression of these three molecules using immunoperoxidase staining and specific antibodies. The authors found a significant increase in the expression of the 67LR and galectin-1 in cancer cells compared with normal adjacent endometrium (P = .0004 and .0022, respectively). As observed in other carcinomas, a significant down-regulation of galectin-3 expression was found in endometrial cancer cells compared with normal mucosa (P = .02). In the galectin-3 positive tumors, galectin-3 was detected in the cytoplasm and/or nucleus of cancer cells. Interestingly, tumors in which galectin-3 was detected only in the cytoplasm were characterized by deeper invasion of the myometrium than lesions where galectin-3 was found both in nucleus and cytoplasm (P = .02). This study shows an alteration of nonintegrin laminin-binding protein expression in advanced human endometrial cancer. Further studies on larger populations should determine the prognostic value of the detection of these laminin-binding proteins in endometrial carcinoma. Inverse modulation of the 67LR and galectin-3 appears to be a phenotypical feature of invasive carcinoma. Copyright (C) 1996 by W.B. Saunders Company C1 UNIV LIEGE, DEPT PATHOL, LIEGE, BELGIUM. NATL FUND SCI RES, BRUSSELS, BELGIUM. DUKE UNIV, MED CTR, DURHAM, NC USA. Scripps Res Inst, DEPT MOL & EXPT MED, LA JOLLA, CA USA. UNIV CALIF SAN FRANCISCO, DEPT ANAT, SAN FRANCISCO, CA 94143 USA. UNIV CALIF SAN FRANCISCO, DEPT PSYCHIAT, SAN FRANCISCO, CA 94143 USA. NCI, PATHOL LAB, MOL PATHOL SECT, BETHESDA, MD 20892 USA. RP VandenBrule, FA (reprint author), UNIV LIEGE, METASTASIS RES LAB, B-4000 LIEGE, BELGIUM. RI Bast, Robert/E-6585-2011 OI Bast, Robert/0000-0003-4621-8462 FU NIAMS NIH HHS [1-R55-AR41459] NR 37 TC 122 Z9 125 U1 0 U2 9 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD NOV PY 1996 VL 27 IS 11 BP 1185 EP 1191 DI 10.1016/S0046-8177(96)90313-5 PG 7 WC Pathology SC Pathology GA VT123 UT WOS:A1996VT12300013 PM 8912829 ER PT J AU Tartakovsky, B Bermas, BL Sthoeger, Z Shearer, GM Mozes, E AF Tartakovsky, B Bermas, BL Sthoeger, Z Shearer, GM Mozes, E TI Defective maternal-fetal interaction in a murine autoimmune model SO HUMAN REPRODUCTION LA English DT Article DE anti-cardiolipin antibodies; anti-phospholipid syndrome; autoimmunity; embryonic implantation; pregnancy ID IN-VITRO FERTILIZATION; SYSTEMIC LUPUS-ERYTHEMATOSUS; ANTIPHOSPHOLIPID ANTIBODIES; PREGNANCY; ANTICARDIOLIPIN; AUTOANTIBODIES; FAILURE; MICE; IMPLANTATION; DISORDERS AB Anti-cardiolipin antibodies (ACA) are associated with recurrent fetal loss, but their role in this pathological condition is unknown, Ne recently developed an experimental mouse model of the anti-phospholipid syndrome, in which immunization of female mise with a monoclonal anti-cardiolipin antibody resulted in substantial failure of pregnancy We observed that pre-implantation embryos derived from ACA-injected mothers exhibited morphological abnormalities and failed to implant in vitro. In the present study we designed embryo transfer experiments to determine whether defective embryonic development originated as a maternal defect, an embryonic defect or both. Embryos (3.5 day old), taken from ACA- and control-immunized mothers were transferred into either an ACA- or a control-treated uterine environment (day 2.5 pseudo-pregnant females). On day 14 of gestation the incidence of pregnancy, the average number of fetuses per female and fetal resorptions were assessed, The ACA-treated uterine environment was found to be non-supportive for the development and implantation of normal embryos, Moreover, embryos derived from ACA-immunized mothers, even after their removal from the ACA-environment and transfer to a normal uterus, remained deficient, These results demonstrate that both the maternal and the embryonic compartments were defective, as a result of previous exposure to the ACA. C1 WEIZMANN INST SCI,DEPT IMMUNOL,IL-76100 REHOVOT,ISRAEL. NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NR 20 TC 29 Z9 31 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD NOV PY 1996 VL 11 IS 11 BP 2408 EP 2411 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA WA428 UT WOS:A1996WA42800017 PM 8981121 ER PT J AU Svetkey, LP McKeown, SP Wilson, AF AF Svetkey, LP McKeown, SP Wilson, AF TI Heritability of salt sensitivity in black Americans SO HYPERTENSION LA English DT Article DE blacks; genetics; hypertension, genetic; sodium ID BLOOD-PRESSURE; SODIUM SENSITIVITY; VOLUME EXPANSION; HYPERTENSION; CONTRACTION; RESISTANCE AB Salt sensitivity is defined as a change in blood pressure in response to changes in salt and water homeostasis. Found in 73% of hypertensive and 36% of normotensive blacks, it is generally considered a hallmark of hypertension in blacks. The higher prevalence of salt sensitivity in blacks compared with whites suggests a genetic influence on this trait, but there is little direct evidence of heritability. We determined the extent to which salt sensitivity is correlated in black families and estimated the heritability of this phenotype. Black families were recruited through a hypertensive proband. Both hypertensive and normotensive adults were phenotyped with respect to salt sensitivity with an intravenous sodium-loading, furosemide volume-depletion protocol. Salt sensitivity was defined as the difference between sodium-loaded and volume-depleted blood pressure. We enrolled 20 families, comprising 30 parent-offspring pairs and 115 adult sibling pairs, Age-adjusted familial correlations ranged from .33 to .44, .19 to .37, and .12 to .21 for mean arterial and systolic and diastolic pressure responses to the salt sensitivity maneuver, respectively. Corresponding heritability estimates were 0.26 to 0.84, 0.26 to 0.74, and 0.004 to 0.24, respectively. These data strongly suggest a heritable component of salt sensitivity. C1 DUKE UNIV,MED CTR,DURHAM,NC. LOUISIANA STATE UNIV,MED CTR,DEPT BIOMETRY & GENET,NEW ORLEANS,LA 70112. NATL INST HLTH,NATL CTR HUMAN GENOME RES,BALTIMORE,MD. RI Wilson, Alexander/C-2320-2009 FU NCRR NIH HHS [M01-RR-30]; NHLBI NIH HHS [R01-HL-50176] NR 29 TC 59 Z9 59 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD NOV PY 1996 VL 28 IS 5 BP 854 EP 858 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VT124 UT WOS:A1996VT12400023 PM 8901834 ER PT J AU Lucas, B Germain, RN AF Lucas, B Germain, RN TI Unexpectedly complex regulation of CD4/CD8 coreceptor expression supports a revised model for CD4(+)CD8(+) thymocyte differentiation SO IMMUNITY LA English DT Article ID T-CELL RECEPTOR; POSITIVE SELECTION; LINEAGE COMMITMENT; CD8 LINEAGE; NEGATIVE SELECTION; INTERMEDIATE STEPS; INSTRUCTIVE MODEL; THYMIC SELECTION; CLONAL DELETION; DEFICIENT MICE AB CD4(+)CD8(+)TCR(lo) thymocytes are the precursors of CD4(+) and CD8(+) mature T cells, whose receptors show specific recognition of peptide-MHC class II and MHC class I complexes, respectively. How T cells emerge from the intrathymic differentiation process with selective expression of either CD8 molecule or CD4 molecule coordinated with the MHC class specificity of the TCR has been the subject of intense examination. Many previous studies of this question have been based on the assumption that extinction of CD4 or CD8 expression by the precursor thymocytes was a steady, uninterrupted process. Here we show that this is an incorrect assumption, with CD4 and CD8 expression undergoing an unexpectedly complex series of expression changes involving down-modulation, kinetically asymmetric up-regulation, and then selective loss. Based on these data, we propose a model for the differentiation pathway of alpha beta TCR thymocytes that explains previous, apparently contradictory findings and establishes useful parameters for future studies at the cellular and gene level. RP Lucas, B (reprint author), NIAID,LYMPHOCYTE BIOL SECT,IMMUNOL LAB,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 67 TC 156 Z9 157 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 1996 VL 5 IS 5 BP 461 EP 477 DI 10.1016/S1074-7613(00)80502-6 PG 17 WC Immunology SC Immunology GA VV658 UT WOS:A1996VV65800007 PM 8934573 ER PT J AU Cain, SA Padlan, EA Helm, BA AF Cain, SA Padlan, EA Helm, BA TI Expression of human IgE-Fc and the extracellular domains of the alpha-chain of the high affinity receptor for IgE in Pichia pastoris. SO IMMUNOLOGY LA English DT Meeting Abstract C1 UNIV SHEFFIELD,KREBS INST,DEPT MOL BIOL & BIOTECHNOL,SHEFFIELD S10 2UH,S YORKSHIRE,ENGLAND. NIDDK,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD NOV PY 1996 VL 89 SU 1 BP C22 EP C22 PG 1 WC Immunology SC Immunology GA VT999 UT WOS:A1996VT99900168 ER PT J AU Helm, BA Machado, DC Sayers, I Padlan, EA AF Helm, BA Machado, DC Sayers, I Padlan, EA TI Applications of rationally designed hIgE-Fc-derived peptides as antagonists of the allergic response SO IMMUNOLOGY LA English DT Meeting Abstract C1 UNIV SHEFFIELD,KREBS INST,DEPT MOL BIOL & BIOTECHNOL,SHEFFIELD S10 2UH,S YORKSHIRE,ENGLAND. NIDDK,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD NOV PY 1996 VL 89 SU 1 BP C24 EP C24 PG 1 WC Immunology SC Immunology GA VT999 UT WOS:A1996VT99900170 ER PT J AU Sayers, I Padlan, EA Helm, BA AF Sayers, I Padlan, EA Helm, BA TI Identification of the sites(s) on human IgE that are involved in the interaction with its high (Fc epsilon RI) and low (Fc epsilon RII) affinity receptor. SO IMMUNOLOGY LA English DT Meeting Abstract C1 UNIV SHEFFIELD,KREBS INST,MBB,SHEFFIELD S10 2UH,S YORKSHIRE,ENGLAND. NIDDK,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD NOV PY 1996 VL 89 SU 1 BP C23 EP C23 PG 1 WC Immunology SC Immunology GA VT999 UT WOS:A1996VT99900169 ER PT J AU McMullen, T Clarke, GF Fleming, E Johnston, J Armstrong, MA AF McMullen, T Clarke, GF Fleming, E Johnston, J Armstrong, MA TI Inhibition of endothelial cell NF kappa B by antioxidant inhibits IL-1B induced activation but not induction by HSV-1 SO IMMUNOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. QUEENS UNIV BELFAST,DEPT MICROBIOL & IMMUNOL,BELFAST BT12 6BN,ANTRIM,NORTH IRELAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD NOV PY 1996 VL 89 SU 1 BP F56 EP F56 PG 1 WC Immunology SC Immunology GA VT999 UT WOS:A1996VT99900202 ER PT J AU Youngs, SJ Ali, SA Taub, DD Rees, RC AF Youngs, SJ Ali, SA Taub, DD Rees, RC TI Chemokines induce migratory responses in human breast carcinoma cell lines. SO IMMUNOLOGY LA English DT Meeting Abstract C1 UNIV SHEFFIELD,SCH MED,INST CANC STUDIES,SHEFFIELD S10 2RX,S YORKSHIRE,ENGLAND. NOTTINGHAM TRENT UNIV,DEPT LIFE SCI,NOTTINGHAM NG11 8NS,ENGLAND. NCI,FREDERICK CANC RES & DEV CTR,MOL IMMUNOREGULAT LAB,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD NOV PY 1996 VL 89 SU 1 BP ORV9 EP ORV9 PG 1 WC Immunology SC Immunology GA VT999 UT WOS:A1996VT99900128 ER PT J AU Wang, LM Patel, B Chen, XH LaRochelle, W Pierce, J AF Wang, LM Patel, B Chen, XH LaRochelle, W Pierce, J TI Signal transduction through the interleukin-4 receptor SO IMMUNOLOGY LA English DT Meeting Abstract C1 NCI,DBS,CELLULAR & MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD NOV PY 1996 VL 89 SU 1 BP SS75 EP SS75 PG 1 WC Immunology SC Immunology GA VT999 UT WOS:A1996VT99900075 ER PT J AU Wolffe, AP AF Wolffe, AP TI The functional specialization of chromatin: Architectural and regulatory roles for histones SO IMMUNOLOGY LA English DT Meeting Abstract ID TRANSCRIPTION C1 NIH,LAB MOL EMBRYOL,BETHESDA,MD 20892. NR 6 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD NOV PY 1996 VL 89 SU 1 BP SA2 EP SA2 PG 1 WC Immunology SC Immunology GA VT999 UT WOS:A1996VT99900002 ER PT J AU Wong, JM Shi, YB Wolffe, AP AF Wong, JM Shi, YB Wolffe, AP TI The thyroid hormone receptor alone is sufficient to target chromatin disruption, but not transcriptional activation SO IMMUNOLOGY LA English DT Meeting Abstract C1 NICHHD,LAB MOL EMBRYOL,NIH,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD NOV PY 1996 VL 89 SU 1 BP SP61 EP SP61 PG 1 WC Immunology SC Immunology GA VT999 UT WOS:A1996VT99900061 ER PT J AU Zhang, Y Sher, A AF Zhang, Y Sher, A TI Role of NK1(+) cells during infection with Toxoplasma gondii SO IMMUNOLOGY LA English DT Meeting Abstract C1 CORNELL UNIV,COLL VET MED,DEPT MICROBIOL & IMMUNOL,ITHACA,NY 14853. NIH,PARASIT DIS LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD NOV PY 1996 VL 89 SU 1 BP SE23 EP SE23 PG 1 WC Immunology SC Immunology GA VT999 UT WOS:A1996VT99900023 ER PT J AU Puck, JM AF Puck, JM TI IL2RGbase: A database of gamma c-chain defects causing human X-SCID SO IMMUNOLOGY TODAY LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; GENE; MUTATIONS; DISEASE; BINDING; CELLS AB X-linked severe combined immunodeficiency (X-SCID) is an immune disorder caused by mutations in the X-linked gene IL2RG, which encodes the common gamma chain of the lymphocyte receptors for interleukin 2 (IL-2) and many other cytokines. A database of human X-SCID mutations (IL2RGbase) has been assembled, and this article summarizes the first 136 entries from unrelated patients. C1 HOP NECKER ENFANTS MALAD,INSERM,U429,PARIS,FRANCE. UNIV ULM,DEPT TRANSFUS MED,D-89081 ULM,GERMANY. RP Puck, JM (reprint author), NIH,NATL CTR HUMAN GENOME RES,LAB GENE TRANSFER,IMMUNOL GENET SECT,BETHESDA,MD 20892, USA. NR 22 TC 59 Z9 60 U1 0 U2 4 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 NOV PY 1996 VL 17 IS 11 BP 507 EP 511 DI 10.1016/0167-5699(96)30062-5 PG 5 WC Immunology SC Immunology GA VU207 UT WOS:A1996VU20700004 PM 8961626 ER PT J AU George, A AF George, A TI Generation of gamma interferon responses in murine Peyer's patches following oral immunization SO INFECTION AND IMMUNITY LA English DT Article ID SALMONELLA-TYPHIMURIUM INFECTION; NECROSIS-FACTOR-ALPHA; NATURAL-KILLER-CELLS; IFN-GAMMA; T-CELLS; CHOLERA-TOXIN; TH2 CELLS; MUCOSAL; MICE; LYMPHOCYTES AB To date, oral immunizations have been shown to generate only Th2 responses in murine Peyer's patches (PP), raising the possibility that T cells present in PP may be capable of mounting only Th2 responses or that the microenvironment of PP does not favor the generation of Th1 cells, However, it is also possible that antigens that can generate Th1 responses have not yet been used for oral immunizations. This study shows that T cells in PP of mice immunized orally with live Salmonella typhimurium secrete large amounts of gamma interferon (IFN-gamma) when they are stimulated with bacterial sonicate in vitro. Moreover, oral challenge of mice with live bacteria 4 months after immunization elicits a secondary IFN-gamma response in PP and mesenteric lymph nodes, Parenteral immunization does not generate an IFN-gamma T-cell response in PP, and parenteral challenge of orally immunized mice does not elicit a secondary response in PP, However, oral challenge of intraperitoneally immunized mice elicits a secondary IFN-gamma response in PP and mesenteric lymph nodes, and intraperitoneal challenge of orally immunized mice elicits a secondary response in the spleen, The data suggest that memory T cells recirculate between mucosal and nonmucosal compartments and that they mag be recruited to the site of antigenic challenge. C1 NIDR,IMMUNOL LAB,BETHESDA,MD 20892. RP George, A (reprint author), NATL INST IMMUNOL,ARUNA ASAF ALI MARG,NEW DELHI 110067,INDIA. NR 34 TC 37 Z9 37 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 NOV PY 1996 VL 64 IS 11 BP 4606 EP 4611 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA VP428 UT WOS:A1996VP42800029 PM 8890214 ER PT J AU Ochoa, MT Valderrama, L Ochoa, A Zea, A Escobar, CE Moreno, LH Falabella, R AF Ochoa, MT Valderrama, L Ochoa, A Zea, A Escobar, CE Moreno, LH Falabella, R TI Lepromatous and tuberculoid leprosy: Clinical presentation and cytokine responses SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Article ID INTERFERON-PRODUCTION; INTERLEUKIN-1; MODULATION; CELLS AB Objective. This study analyzes the major clinical characteristics of patients with active leprosy in relation to the in vitro immune response to the T-lymphocyte activator anti-CD3. Methods. Thirty-eight patients with an established diagnosis of leprosy were classified according to the Ridley and Jopling table. Peripheral blood mononuclear cells from both lepromatous leprosy (LL) and tuberculoid leprosy (TL) patients and healthy controls were used to evaluate lymphocyte proliferation; immunoenzymatic assays were used to evaluate cytokine production (IL-1, IL-2, IL-4, IL-6, IL-10, IFN-gamma). Results. Peripheral blood mononuclear cells from both LL and TL patients displayed blastogenic responses to anti-CD3. The cytokines IL-1 beta, IL-6, IL-10, and IFN-gamma were detected in culture supernatants. Endogenous production of IL-18 was significantly higher in cell cultures from patients with the lepromatous form of the disease compared to those with tuberculoid leprosy. Production of IL-6 in response to anti-CD3 was observed in a significantly higher proportion of LL than TL patients (P = 0.0025). Gamma-interferon production did not differ between TL and LL, but a direct correlation was observed between time of multidrug treatment and IFN production in vitro (P = 0.016). Interleukin-10 was detected in culture supernatants of lymphocytes activated by anti-CDS from both patient groups, but not from healthy controls. Conclusions. The findings of this study suggest that patients with the two distinct forms of leprosy are capable of responding to a polyclonal T-lymphocyte stimulus such as anti-CD3 and provide evidence suggestive of alterations in the immune responses mediated by cytokines that may contribute to the spectrum of disease and response to treatment. C1 UNIV VALLE,DERMATOL SERV,CALI,COLOMBIA. NCI,IMMUNOTHERAPY LAB,FREDERICK,MD 21701. SECRETARIA DEPT SALUD,LEPROSY CLIN,CALI,COLOMBIA. RP Ochoa, MT (reprint author), CTR INT ENTRENAMIENTO & INVEST MED,AA 5390,CALI,COLOMBIA. FU NIAID NIH HHS [5P50 AI 30603-05] NR 22 TC 11 Z9 11 U1 0 U2 1 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON ON L8N 3K7, CANADA SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD NOV PY 1996 VL 35 IS 11 BP 786 EP 790 DI 10.1111/j.1365-4362.1996.tb02974.x PG 5 WC Dermatology SC Dermatology GA VQ937 UT WOS:A1996VQ93700006 PM 8915730 ER PT J AU Black, PL McKinnon, KM Wooden, SL Ussery, MA AF Black, PL McKinnon, KM Wooden, SL Ussery, MA TI Antiviral activity of biological response modifiers in a murine model of AIDS. Requirement for augmentation of natural killer cell activity and synergy with oral AZT SO INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY LA English DT Article DE AIDS; animal model; Rauscher murine leukemia virus; biological response modifier(s); interferon inducer(s) ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNE-DEFICIENCY SYNDROME; TRIHYDROCHLORIDE CL 246,738; INTERFERON-ALPHA; NK-CELLS; HIV-INFECTION; KAPOSIS-SARCOMA; SELECTIVE DEPLETION; HOMOSEXUAL MEN; LEUKEMIA-VIRUS AB We employed the Rauscher murine leukemia virus (RMuLV) as a murine retrovirus model of AIDS, to test biological response modifiers (BRM) and antiviral agents for potential therapeutic activity against the human immunodeficiency virus (HIV). We examined the relationship between the augmentation of natural killer (NK) cell activity and antiviral efficacy of a series of BRM, most of which are known inducers of interferon, in this model. Poly [I,C]-LC, MVE-2, and CL 246,738, but not Ampligen, soluble glucan, or 7-thia-8-oxoguanosine, consistently produced antiviral activity. In addition, the combination of suboptimal doses of oral 3'-azido-3'-deoxythymidine (AZT) (in drinking water) and poly [I,C]-LC produced a synergistic antiviral effect. With all the BRM tested, a consistent pattern emerged, namely that antiviral activity always correlated with the augmentation of splenic NK cell activity in infected animals. For instance, poly [I,C]-LC boosted NK activity much more in infected mice treated therapeutically (treatment initiated after infection) than prophylactically (treatment initiated before infection), and it had greater antiviral activity therapeutically than prophylactically. For the BRM tested, antiviral activity did not occur without augmentation of NK activity in infected mice. In contrast, augmentation of NK activity in uninfected mice bore no relationship to antiviral activity. Furthermore, elimination of NK cells by treating mice with anti-asialo GM(1) abolished the antiviral activity of poly [I,C]-LC. Although splenic NK activity was ablated by anti-asialo GM(1), serum interferon levels were not affected by this treatment. These results point to a causal connection between the augmentation of NK cell activity and the antiviral efficacy of these BRM in this murine AIDS model. NK cells thus appear to play a key role in resistance to this retrovirus, as has been suggested for HIV. (C) 1997 International Society for Immunopharmacology. C1 US FDA,CTR DRUG EVALUAT & RES,DIV ANTIVIRAL DRUG PROD,ROCKVILLE,MD 20857. RP Black, PL (reprint author), SO RES INST,FREDERICK CANC RES CTR,FREDERICK,MD, USA. FU NIAID NIH HHS [1U01AI25617] NR 64 TC 8 Z9 9 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0192-0561 J9 INT J IMMUNOPHARMACO JI Int. J. Immunopharmacol. PD NOV PY 1996 VL 18 IS 11 BP 633 EP 650 DI 10.1016/S0192-0561(96)00064-1 PG 18 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA WP701 UT WOS:A1996WP70100003 PM 9089007 ER PT J AU Tataranni, PA Pettitt, DJ Ravussin, E AF Tataranni, PA Pettitt, DJ Ravussin, E TI Dual energy X-ray absorptiometry: Inter-machine variability SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE dual energy X-ray absorptiometry; body composition; reproducibility; inter-machine variability ID BODY-COMPOSITION; ACCURACY AB OBJECTIVE: Dual-energy X-ray absorptiometry (DEXA) is rapidly becoming the method of choice for body composition measurements. We tested inter-machine variability because large differences in body composition measurements between different DEXA machines have recently been reported. DESIGN: Comparison of total body scans using 2 DEXA machines from the same manufacturer (DPX-L: Lunar Co, Madison, WI) on 10 volunteers (5M/5F). RESULTS: We observed statistically significant differences between the 2 machines for all mean values of body composition variables as a result of a systematic underestimation of bone mineral and overestimation of fat tissue by one machine vs the other. However, the magnitude of the observed differences was small (namely bone mineral +68 +/- 57 g; percent body fat -1.7 +/- 1%, Mean +/- s.d.). CONCLUSION: Differences do exist in the performances of 2 DEXA machines from the same manufacturer. Although the differences reported in the present study are small, emphasis should be given in pre-testing machines when multiple apparatuses are used in a study. Also, because the observed error was systematic, randomized designs are necessary when more than one DEXA machine is used in longitudinal/intervention study. Better yet manufacturers of DEXA machine should standardize their equipments to ensure the best consistency between machines. C1 NIDDKD, NIH, DIABET & ARTHRITIS EPIDEMIOL SECT, PHOENIX, AZ 85016 USA. RP Tataranni, PA (reprint author), NIDDKD, CLIN DIABET & NUTR SECT, NIH, 4212 N 16TH ST, RM 541-A, PHOENIX, AZ 85016 USA. NR 6 TC 21 Z9 21 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD NOV PY 1996 VL 20 IS 11 BP 1048 EP 1050 PG 3 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA VP079 UT WOS:A1996VP07900012 PM 8923164 ER PT J AU Srivastava, RK Srivastava, AR ChoChung, YS AF Srivastava, RK Srivastava, AR ChoChung, YS TI Multidrug resistance in cancer (review) SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE MDR; PKA; PKC; 8-Cl-cAMP; cancer; multidrug resistance; transcription; P-glycoprotein ID PROTEIN-KINASE-C; P-GLYCOPROTEIN PHOSPHORYLATION; BACTERIAL TRANSPORT PROTEINS; MDR GENE FAMILY; DRUG-RESISTANCE; MESSENGER-RNA; RESPONSIVE ELEMENT; CHLORIDE CHANNELS; CARCINOMA-CELLS; EXPRESSION AB The development of resistance to anticancer agents during treatment is a major obstacle in the chemotherapy of cancer. Cells expressing high levels of the P-glycoprotein exhibit a multidrug resistance phenotype. The P-glycoprotein is a membrane phosphoprotein which serves as a drug efflux pump to reduce intracellular drug accumulation, and hence the cytotoxicity of anticancer drugs. Several studies have shown that protein kinase activators and inhibitors may modulate the biological activity of P-glycoprotein through covalent modification by phosphorylation. Most of these drugs may have additional mechanisms of action and may alter drug accumulation within multidrug resistant cells with or without their effects on phosphorylation of P-glycoprotein. In addition, transcriptional regulation of MDR 1 gene has been found to be regulated by protein kinase A type I and protein kinase C. Therefore, these kinases may be important candidates in studies of the reversal of multidrug resistance and hence in enhancing the efficacy of anticancer drugs. C1 NCI,CELLULAR BIOCHEM SECT,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892. NR 76 TC 9 Z9 9 U1 0 U2 1 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 NOV PY 1996 VL 9 IS 5 BP 879 EP 884 PG 6 WC Oncology SC Oncology GA VP104 UT WOS:A1996VP10400002 PM 21541590 ER PT J AU Saxena, A Robertson, JT Ali, IU Schweitzer, JB AF Saxena, A Robertson, JT Ali, IU Schweitzer, JB TI Prognostic significance of multiple genetic lesions on chromosomes 19, 10, and 17 in oligodendrogliomas SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE oligodendroglioma; oligoastrocytoma ID TUMOR-SUPPRESSOR GENE; HUMAN GLIOMAS; GLIOBLASTOMA-MULTIFORME; HUMAN ASTROCYTOMAS; DISTINCT REGIONS; MIXED GLIOMAS; CELL; P53; HETEROZYGOSITY; DELETIONS AB Patients diagnosed with oligodendrogliomas/oligoastrocytomas and with somatic loss of genes on chromosome 19q13.2-q13.3 survived for >5-6 years, a survival period typical of the tumors of oligodendroglial origin. One patient with oligoastrocytoma, harboring allelic loss on chromosome 10p in the tumor DNA, had a recurrence five years later with progression to anaplastic astrocytoma. However, another patient with oligoastrocytoma, whose tumor suffered multiple genetic lesions on chromosomes 19q13.2-13.3, 10q22-24, and 17p13.1 (a point mutation in the p53 gene), had two subsequent recurrences as anaplastic astrocytomas and a survival period of 29 months. Our data suggest that in tumors of oligodendroglial origin the inactivation of a tumor suppressor gene on chromosome 10, especially in conjunction with other genetic aberrations, is indicative of aggressive clinical course. C1 NCI,LGD,FCRDC,NIH,FREDERICK,MD 21702. NINCDS,SURG NEUROL BRANCH,NIH,BETHESDA,MD 20892. UNIV TENNESSEE,DEPT PATHOL,MEMPHIS,TN 38119. UNIV TENNESSEE,DEPT NEUROSURG,MEMPHIS,TN 38119. NR 37 TC 0 Z9 0 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 NOV PY 1996 VL 9 IS 5 BP 901 EP 905 PG 5 WC Oncology SC Oncology GA VP104 UT WOS:A1996VP10400005 PM 21541593 ER PT J AU Sakamoto, H Kodama, H Higashimoto, Y Kondo, M Lewis, MS Anderson, CW Appella, E Sakaguchi, K AF Sakamoto, H Kodama, H Higashimoto, Y Kondo, M Lewis, MS Anderson, CW Appella, E Sakaguchi, K TI Chemical synthesis of phosphorylated peptides of the carboxy-terminal domain of human p53 by a segment condensation method SO INTERNATIONAL JOURNAL OF PEPTIDE AND PROTEIN RESEARCH LA English DT Article DE phosphopeptide synthesis; segment condensation method; peptide thioester; p53; tumor suppressor protein; tetramerization domain; regulatory domain; analytical ultracentrifugation; CD spectroscopy ID SOLID-PHASE SYNTHESIS; DNA-BINDING FUNCTION; PROTEIN SECONDARY STRUCTURE; TUMOR-SUPPRESSOR P53; S-ALKYL THIOESTER; OLIGOMERIZATION DOMAIN; EFFICIENT PROCEDURE; GROWTH ARREST; PHOSPHOPEPTIDES; ACID AB A segment condensation method was developed for the chemical synthesis of large (>90 amino acid) phosphopeptides and was used to produce phosphorylated and non-phosphorylated derivatives of the C-terminal tetramerization and regulatory domains of human p53 (residues 303-393). Efficient condensation synthesis of the 91 residue p53 domain was achieved in two steps. The non-phosphorylated N-terminal segment p53(303-334) (1) and its derivative phosphorylated at serine 315 (1P315), and the nonphosphorylated middle segment p53(335-360) (2), were synthesized as partially protected peptide thioesters in the solid phase using Boc chemistry. The C-terminal segment p53(361-393) (3) and its derivative phosphorylated at serine 392 (3P392) were synthesized as partially protected peptides in the solid phase using Fmoc chemistry. Phosphoamino acid was incorporated into the N-terminal segment (1P315) at the residue corresponding to p53 serine 315 as Boc-Ser(PO3(Bzl)(2))-OH during synthesis. Serine 392 in the C-terminal segment was selectively phosphorylated after synthesis by phosphitylation followed by oxidation. A derivative phosphorylated at serine 378 was synthesized in a one-step condensation of the unphosphorylated N-terminal segment (1) and the phosphorylated long C-terminal segment p53(335-393) (2-3P378). Yields of the ligated peptides after removal of the protecting groups and HPLC purification averaged 60% for the first condensation and 35% for the second condensation. All five p53 peptides exhibited monomer-tetramer association as determined by analytical ultracentrifugation. Circular dichroism spectroscopy revealed that phosphorylation at Ser315 increased the alpha-helical content, which was abolished when Ser392 also was phosphorylated, suggesting an interaction between N-terminal and C-terminal residues of the C-terminal domain of p53. (C) Munksgaard 1996. C1 NCI, NATL INST HLTH, CELL BIOL LAB, BETHESDA, MD 20892 USA. SAGA UNIV, FAC SCI & ENGN, BIOCHEM LAB, SAGA 840, JAPAN. NIH, BIOMED ENGN & INSTRUMENTAT PROGRAM, BETHESDA, MD 20892 USA. BROOKHAVEN NATL LAB, DEPT BIOL, UPTON, NY 11973 USA. RI Sakamoto, Hiroshi/A-3181-2011 NR 46 TC 18 Z9 18 U1 1 U2 4 PU BLACKWELL MUNKSGAARD PI FREDERIKSBERG C PA 1 ROSENORNS ALLE, DK-1970 FREDERIKSBERG C, DENMARK SN 0367-8377 J9 INT J PEPT PROT RES JI Int. J. Pept. Protein Res. PD NOV PY 1996 VL 48 IS 5 BP 429 EP 442 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VV739 UT WOS:A1996VV73900004 PM 8956076 ER PT J AU Wistow, G AF Wistow, G TI Untitled SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Letter RP Wistow, G (reprint author), NEI,NIH,BETHESDA,MD 20892, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 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 NOV PY 1996 VL 37 IS 12 BP 2363 EP 2364 PG 2 WC Ophthalmology SC Ophthalmology GA VT378 UT WOS:A1996VT37800001 PM 8933752 ER PT J AU Tamm, ER Russell, P Johnson, DH Piatigorsky, J AF Tamm, ER Russell, P Johnson, DH Piatigorsky, J TI Human and monkey trabecular meshwork accumulate alpha B-crystallin in response to heat shock and oxidative stress SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE anterior eye segment; crystallin; Northern blot analysis; small heat shock protein; tire-dimensional gel electrophoresis ID ALEXANDERS DISEASE BRAIN; HUMAN GLIOMA-CELLS; MOLECULAR CHAPERONES; OUTFLOW FACILITY; ROSENTHAL FIBERS; AQUEOUS-HUMOR; PROTEIN; EXPRESSION; LENS; PHOSPHORYLATION AB Purpose. Oxidative stress and other forms of injury to trabecular meshwork (TM) cells may contribute to changes seen with age and primary open-angle glaucoma. This study was designed to investigate if TM expresses alpha B-crystallin, a small heat-shock protein with chaperone activity, and whether it might be overexpressed under stress conditions. Methods. The TM from human and monkey eyes, as well as organ and primary cell cultures derived from these eyes, were investigated for alpha B-crystallin by immunohistochemistry, two-dimensional gel electrophoresis, Northern and Western blot analysis. The TM cell cultures were stressed by heat shock (44 degrees C for 15 minutes) or hydrogen peroxide (200 mu mol for 1 hour). Semiquantitation of alpha B-crystallin messenger RNA (mRNA) or protein was obtained by densitometry. Results. In both species, alpha B-crystallin could be detected in fresh and cultured TM by two-dimensional gel electrophoresis in conjunction with Western blot analysis. Immunohistochemistry of fresh samples showed that alpha B-crystallin was expressed predominantly in the cribriform area. Protein expression was enhanced in 4- to 7-day organ cultures. Primary cultures from human TM cells expressed two sizes (approximately 0.8 and 1.1 kb) of alpha B-crystallin mRNA in Northern blots. In monkey TM cultures, a 0.8-kb band was observed, which comigrated with lens alpha B-crystallin. In both species, heat shuck caused a significant increase in alpha B-crystallin mRNA with a peak after 4 hours. An increase in alpha B-crystallin mRNA also was observed after oxidative stress; however, the onset of mRNA induction was slower. After heat shock, but not after oxidative stress, a transient change in mRNA mobility was observed. Western dot blot analysis showed a 3.4-fold increase in protein 24 hours after heat shock and a 20-fold increase after 48 hours. No constitutive mRNA expression and only a minimal increase 4 hours after heat shock could be observed in simian virus 40 transformed cell lines from human TM. Conclusions Overexpression of alpha B-crystallin might be an important mechanism for TM to prevent cellular damage associated with various stress conditions. C1 NEI,NIH,LAB MECHANISMS OCULAR DIS,BETHESDA,MD 20892. MAYO CLIN,DEPT OPHTHALMOL,ROCHESTER,MN. RP Tamm, ER (reprint author), NEI,NIH,LAB MOL & DEV BIOL,6 CTR DR,MSC 2730,BLDG 6,ROOM 204,BETHESDA,MD 20892, USA. NR 67 TC 73 Z9 77 U1 0 U2 2 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 NOV PY 1996 VL 37 IS 12 BP 2402 EP 2413 PG 12 WC Ophthalmology SC Ophthalmology GA VT378 UT WOS:A1996VT37800009 PM 8933757 ER PT J AU Ellwein, LB Kroll, P Narin, F AF Ellwein, LB Kroll, P Narin, F TI Linkage between research sponsorship and patented eye-care technology SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE eye-care; patents; science references; sponsored research; technology ID SCIENCE AB Purpose. To examine the linkage between the funding of ophthalmologic and related biomedical research and the development of patented eye-care technology using data on patents granted and the scientific literature cited by those patents. Methods. The United States patents granted during the 20-year period from 1975 through 1994 were screened using patent office classifications and key words to identify all eye-care-related patents. Each patent's nonpatent references (references to literature other than previously granted patents) were examined, and those references to scientific papers then were reviewed to determine the authors' institutions and acknowledged funding sources. Results. Major findings include the following: (1) Eye technology innovation has grown steadily, with a threefold increase in number of patents granted from 224 in 1975 to 662 in 1994. (2) The cited scientific base that supports this technology has grown even more rapidly, with a sixfold increase in the average number of nonpatent references, from fewer than 0.5 per patent in 1975 to more than 3.0 in 1994; as a result, the total number of nonpatent references has increased by a factor of 20, from 100 in 1975 to 2000 in 1994. (3) The National Eye Institute is the leading single institution in providing support for this research: 31% of all eye-care patents with science references cite papers that contain at least one acknowledgment to National Eye Institute (NEI) support; and when NEI is combined with the rest of the National Institutes of Health (NIH), 41% of the patents with science references are linked to NIH-funded research. (4) Patent science dependence, as measured by science references, is greatest for technologies related to medical treatment, surgical instruments, and intraocular lenses; moderate for diagnostic instruments and contact lens; and least for eyeglasses. Conclusions. The NIH and other sponsored vision research is of direct and increasing relevance to the growing number of US patented eye-care technologies. C1 CHI RES,HADDON HTS,NJ. RP Ellwein, LB (reprint author), NEI,31 CTR DR,MSC 2510,BETHESDA,MD 20892, USA. FU NEI NIH HHS [N01-EY-3-2138] NR 10 TC 3 Z9 3 U1 0 U2 2 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 NOV PY 1996 VL 37 IS 12 BP 2495 EP 2503 PG 9 WC Ophthalmology SC Ophthalmology GA VT378 UT WOS:A1996VT37800018 PM 8933766 ER PT J AU Cole, PM ZahnWaxler, C Fox, NA Usher, BA Welsh, JD AF Cole, PM ZahnWaxler, C Fox, NA Usher, BA Welsh, JD TI Individual differences in emotion regulation and behavior problems in preschool children SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID REPORTED ANXIOUS SYMPTOMS; CONDUCT DISORDER; RATING-SCALE; FOLLOW-UP; PERSPECTIVE; DIFFERENTIATION; ANTECEDENTS; RESPONSES; STABILITY; INFANTS AB Emotion regulation (ER) was assessed during a negative mood induction in 79 preschoolers who varied in degree of behavior problems. Facial expressivity during the induction was used to identify 3 ER groups: inexpressive, modulated expressive, and highly expressive. Group differences in ER were significantly related to heart rate and skin conductance. Inexpressive preschoolers had the highest heart rate, lowest vagal tone, and smallest autonomic nervous system (ANS) change during the induction. Highly expressive preschoolers had the slowest heart rate, highest vagal tone, and largest ANS change. The inexpressive and highly expressive groups had more externalizing symptoms than the modulated group at preschool age and at follow-up at the end of 1 st grade. Inexpressive preschoolers appeared to have more depressed and anxious symptoms at follow-up. C1 NIMH,SECT DEV PSYCHOL,BETHESDA,MD 20892. UNIV MARYLAND,DEPT HUMAN DEV,COLLEGE PK,MD 20742. RP Cole, PM (reprint author), PENN STATE UNIV,DEPT PSYCHOL,417 BRUCE V MOORE BLDG,UNIVERSITY PK,PA 16802, USA. NR 74 TC 151 Z9 152 U1 3 U2 31 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 NOV PY 1996 VL 105 IS 4 BP 518 EP 529 DI 10.1037/0021-843X.105.4.518 PG 12 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA VQ840 UT WOS:A1996VQ84000004 PM 8952185 ER PT J AU Japour, AJ Lertora, JJ Meehan, PM Erice, A Connor, JD Griffith, BP Clax, PA HoldenWiltse, J Hussey, S Walesky, M Cooney, E Pollard, R Timpone, J McLaren, C Johanneson, N Wood, K Booth, DK Bassiakos, Y Crumpacker, CS AF Japour, AJ Lertora, JJ Meehan, PM Erice, A Connor, JD Griffith, BP Clax, PA HoldenWiltse, J Hussey, S Walesky, M Cooney, E Pollard, R Timpone, J McLaren, C Johanneson, N Wood, K Booth, DK Bassiakos, Y Crumpacker, CS TI A phase-I study of the safety, pharmacokinetics, and antiviral activity of combination didanosine and ribavirin in patients with HIV-1 disease SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE didanosine; HIV-1; phase-I study; ribavirin ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMP DEHYDROGENASE STIMULATE; INFECTED PATIENTS; TRIAL; 2',3'-DIDEOXYINOSINE; TYPE-1; ASSAY; 2',3'-DIDEOXYNUCLEOSIDES; ZIDOVUDINE; INVITRO AB A phase-I study was conducted to examine the safety, pharmacokinetics, and activity of combination 2',3'-dideoxyinosine (ddI) and ribavirin against human immunodeficiency virus type 1 (HIV-1)-positive individuals with CD4+ cell counts of less than or equal to 500/mu 1. Nineteen patients were enrolled into the study in which ddI monotherapy (200 mg p.o. b.i.d.) was administered for the first 4 weeks, followed by the coadministration of ribavirin (600 mg p.o. q.d,) and ddI (200 mg p.o. b.i.d.) for 8 or 20 additional weeks. The combination regimen was safe and well tolerated. Three patients did not complete 12 weeks of the study because of adverse events or voluntary withdrawal. The pharmacokinetic studies performed at weeks 4, 6, and 12 on specimens collected from the 15 individuals who completed 12 weeks of therapy revealed no pharmacokinetic interaction between ddI and ribavirin, A significant decline from baseline in HIV-1 titer as measured by quantitative HIV-1 culture was detected both during the ddI-monotherapy phase (week 4, p < 0.001) and during the combination-therapy ddI + ribavirin phase (week 12, p < 0.001); the median drop observed was 0.90 log(10) at week 4 and 0.92 log(10) at week 12. While the addition of ribavirin did not result in further reductions in viremia in the following weeks on study treatment, 13 (81%) of the 16 patients had at least a -0.5 log(10) change in viral titer at week 12. The median decline in plasma viral RNA was 0.68 log(10) at week 4 (p < 0.001) and 0.67 log(10) at week 12 (p = 0.005), CD4+ cell counts increased above baseline significantly during the ddI-monotherapy phase of the study (p = 0.0038). The median increase was +26 cells/mm(3) at week 4 and + 11 cells/mm(3) at week 12; for patients who remained on treatment through 24 weeks, the median CD4+ cell count increase was + 10 cells/mm(3). The L74V ddI resistance-conferring HIV-1 reverse-transcriptase mutation emerged in 53% of the patients. Patients with non-syncytium-inducing HIV variants demonstrated greater responses to treatment with larger decreases in virus load and greater increases in CD4+ cell count. Our results reveal that the combination of ddI and ribavirin in HIV-positive patients is safe, well tolerated, without adverse pharmacologic interaction, and associated with significant and sustained declines in virus load over 12 weeks of therapy. C1 TULANE UNIV,SCH MED,NEW ORLEANS,LA 70118. HARVARD UNIV,SCH PUBL HLTH,STAT DATA CTR,BOSTON,MA 02115. FRONTIER SCI & TECHNOL RES FDN INC,AMHERST,NY. UNIV MINNESOTA,SCH MED,MINNEAPOLIS,MN 55455. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. YALE UNIV,SCH MED,NEW HAVEN,CT. VET ADM CONNECTICUT HEALTHCARE SYST,W HAVEN,CT. NIAID,DIV AIDS,NIH,BETHESDA,MD 20892. UNIV TEXAS,MED BRANCH,GALVESTON,TX 77550. BRISTOL MYERS SQUIBB CO,WALLINGFORD,CT 06492. ICN PHARMACEUT,COSTA MESA,CA. RES TRIANGLE INST,DURHAM,NC. RP Japour, AJ (reprint author), HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DIV INFECT DIS DANA 617,330 BROOKLINE AVE,BOSTON,MA 02215, USA. FU NIAID NIH HHS [AI-01101, AI-32766, AI-27659] NR 36 TC 35 Z9 36 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 NOV 1 PY 1996 VL 13 IS 3 BP 235 EP 246 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA VQ223 UT WOS:A1996VQ22300005 PM 8898668 ER PT J AU Gupta, N Martin, BM Metcalfe, DD Rao, PVS AF Gupta, N Martin, BM Metcalfe, DD Rao, PVS TI Parthenium pollen SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Parthenium; glycoprotein; allergen; hydroxyproline ID LOLIUM-PERENNE; ALLERGENS; HYSTEROPHORUS; PROTEINS; GLYCOPROTEIN; IGE; PURIFICATION; IDENTIFICATION; CARBOHYDRATE; TROPOMYOSIN AB Background: The airborne pollen of the Compositae weed, Parthenium hysterophorus, is a major cause of allergic rhinitis in the Indian subcontinent and in certain parts of the southern United States and western Australia. Earlier studies have identified a 31 kd protein as the major allergen in Parthenium pollen. Objective: This study was undertaken to carry out the purification, immunochemical characterization, sequencing and epitope analysis of this major allergen, designated as Pal h 1. Methods: The IgE-binding activity of the allergen was evaluated by immunoblot and inhibition ELISAs. Pronase digestion, periodate oxidation, and chemical deglycosylation were performed to determine the role of peptide and carbohydrate components of the allergen-in IgE binding. Results: The data provide evidence for the involvement of carbohydrate moieties on Par h 1 in its IgE-binding ability. The N-terminal 91 amino acid sequence of Par h 1 shows 81% identity with a protein from sunflower anther, and the hydroxyproline-rich region of Par h 1 is 30% to 40% identical to similar stretches in extensins, a class of hydroxyproline-rich cell wall glycoproteins from different plant species. IgE antibodies in the sera of individuals allergic to Parthenium cross-reacted with a 50 kd hydroxproline-arabinose-rich extensin precursor from potato tuber, and this binding was periodate-sensitive. Conclusions: It appears that a group of soluble plant glycoproteins, which are related td the ubiquitous extensins, have certain car carbohydrate-containing IgE-binding epitopes that may contribute to allergenic cross-reactivity among specific pollens and foods. C1 INDIAN INST SCI,DEPT BIOCHEM,LAB IMMUNOL & ALLERG DIS,BANGALORE 560012,KARNATAKA,INDIA. NIMH,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. NIAID,ALLERG DIS SECT,NIH,BETHESDA,MD 20892. NR 36 TC 19 Z9 19 U1 1 U2 4 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD NOV PY 1996 VL 98 IS 5 BP 903 EP 912 DI 10.1016/S0091-6749(96)80006-6 PN 1 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA VU764 UT WOS:A1996VU76400006 PM 8939153 ER PT J AU Heishman, SJ Singleton, EG Crouch, DJ AF Heishman, SJ Singleton, EG Crouch, DJ TI Laboratory validation study of drug evaluation and classification program: Ethanol, cocaine, and marijuana (vol 20, pg 468, 1996) SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Correction, Addition RP Heishman, SJ (reprint author), NIDA,ADDICT RES CTR,BIOL DEPENDENCE SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 1 TC 0 Z9 0 U1 0 U2 2 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 NOV-DEC PY 1996 VL 20 IS 7 BP A16 EP A16 PG 1 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA VT933 UT WOS:A1996VT93300017 ER PT J AU Gerber, JS Hinton, DM AF Gerber, JS Hinton, DM TI An N-terminal mutation in the bacteriophage T4 motA gene yields a protein that binds DNA but is defective for activation of transcription SO JOURNAL OF BACTERIOLOGY LA English DT Article ID RNA-POLYMERASE; ESCHERICHIA-COLI; EXPRESSED PROTEIN; PROMOTER; MUTANTS; PURIFICATION; SEQUENCE; DOMAINS; CLONING; REGIONS AB The bacteriophage T4 MotA protein is a transcriptional activator of T4-modified host RNA polymerase and is required for activation of the middle class of T4 promoters, MotA alone binds to the -30 region of T4 middle promoters, a region that contains the MotA box consensus sequence [(t/a)(t/a)TGCTT(t/c)A], We report the isolation and characterization of a protein designated Mot21, in which the first 8 codons of the wild-type motA sequence have been replaced with 11 different codons, In gel retardation assays, Mot21 and MotA bind DNA containing the T4 middle promoter P-uvsX similarly, and the proteins yield similar footprints on P-uvsX. However, Metal is severely defective in the activation of transcription, On native protein gels, a new protein species is seen after incubation of the sigma(70) subunit of RNA polymerase and wild-type MotA protein, suggesting a direct protein-protein contact between MotA and sigma(70), Mot21 fails to form this complex, suggesting that this interaction is necessary for transcriptional activation and that the Mot21 defect arises because Mot21 cannot form this contact like the wild-type activator. C1 NIDDKD,SECT NUCL ACID BIOCHEM,CELLULAR & MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 47 TC 36 Z9 36 U1 0 U2 1 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 NOV PY 1996 VL 178 IS 21 BP 6133 EP 6139 PG 7 WC Microbiology SC Microbiology GA VP984 UT WOS:A1996VP98400007 PM 8892810 ER PT J AU Nakahara, H Nomizu, M Akiyama, SK Yamada, Y Yeh, YY Chen, WT AF Nakahara, H Nomizu, M Akiyama, SK Yamada, Y Yeh, YY Chen, WT TI A mechanism for regulation of melanoma invasion - Ligation of alpha(6)beta(1) integrin by laminin G peptides SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-TRANSDUCTION; CELL-ADHESION; TYROSINE PHOSPHORYLATION; EXTRACELLULAR-MATRIX; SYNTHETIC PEPTIDES; BETA-1 INTEGRINS; IV COLLAGENASE; SCATTER FACTOR; A CHAIN; FIBRONECTIN AB Invasion of LOX human melanoma cells involves extracellular matrix (ECM) degradation and formation of cell surface invadopodia. Here we show that the ligation of alpha(6) beta(1) by two peptides derived from the COOH-terminal globular domain of laminin-1 alpha(1) chain (laminin G peptides), designated AG-10 (NPWHSIYITRFG) and AG-32 (TWYKIAFQRNRK), and antibodies against alpha(6) and beta(1) integrins promoted invasiveness. AG-10 and AG-SB inhibited cell adhesion on laminin, and the antibodies blocked cell adhesion on immobilized AG-10 and AG-32, suggesting that the peptides interact primarily with alpha(6) beta(1) integrin. These soluble peptides and integrin antibodies induced invasiveness by causing an 2-3-fold increase in ECM degradation and invadopodial activity independently of adhesion activity of integrins that were prebound to ECM. The induced ECM degradation and invasion was associated with an increased surface expression of the 170-kDa membrane-bound gelatinase, seprase, as well as its intense localization at invadopodia but not at focal adhesions. However, the total expression levels of seprase, gelatinase A and beta(1) integrins were not altered. We suggest that laminin G peptides act on the alpha(6) beta(1) integrin signaling of invasion by stimulating invadopodial activities, which is distinct from their direct effects on cell adhesion on immobilized ECM. C1 GEORGETOWN UNIV,MED CTR,LOMBARDI CANC CTR,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,DEPT CELL BIOL,WASHINGTON,DC 20007. NIDR,DEV BIOL LAB,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [R01 CA-39077] NR 30 TC 90 Z9 92 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 1 PY 1996 VL 271 IS 44 BP 27221 EP 27224 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VQ679 UT WOS:A1996VQ67900009 PM 8910291 ER PT J AU Teramoto, H Coso, OA Miyata, H Igishi, T Miki, T Gutkind, JS AF Teramoto, H Coso, OA Miyata, H Igishi, T Miki, T Gutkind, JS TI Signaling from the small GTP-binding proteins Rac1 and Cdc42 to the c-Jun N-terminal kinase stress-activated protein kinase pathway - A role for mixed lineage kinase 3 protein-tyrosine kinase 1, a novel member of the mixed lineage kinase family SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SH3 DOMAIN; IDENTIFICATION; CLONING; SUBFAMILY; CASCADE; BEARING; BRAIN AB Certain small GTP-binding proteins control the enzymatic activity of a family of closely related serine-threonine kinases known as mitogen-activated protein kinases (MAPKs), In turn, these MAPKs, such as p44(mapk) and p42(mapk), referred to herein as MAPKs, and stress activated protein kinases, also termed c-Jun N-terminal kinases (JNKs), phosphorylate and regulate the activity of key molecules that ultimately control the expression of genes essential for many cellular processes, Whereas Ras controls the activation of MAPK, we and others have recently observed that two members of the Rho family of small GTP-binding proteins, Rad and Cdc42, regulate the activity of JNKs. The identity of molecules communicating Rad and Cdc42 to JNK is still poorly understood. It has been suggested that Pak1 is the most upstream kinase connecting these GTPases to JNK; however, we have observed that coexpression of Pak1 with activated forms of Cdc42 or Rad diminishes rather than enhances JNK activation. This prompted us to explore the possibility that kinases other than Pak might participate in signaling from GTP binding proteins to JNK, In this regard, a computer-assisted search for proteins containing areas of homology to that in Pak1 that is involved in binding to Rad and Cdc42 led to the identification of mixed lineage kinase 3 (MLK3), also known as protein-tyrosine kinase 1, as a potential candidate for this function, In this study, we found that MLK3 overexpression is sufficient to activate JNK po tently without affecting the phosphorylating activity of MAPK or p38. Furthermore, we present evidence that MLK3 binds the GTP-binding proteins Cdc42 and Rad in vivo and that MLK3 mediates activation of MEKK-SEK-JNK kinase cascade by Rad and Cdc42. Taken together, these findings strongly suggest that members of the novel MLK family of highly related kinases link small GTP-binding proteins to the JNK signaling pathway. C1 NIDR,CELLULAR DEV & ONCOL LAB,MOL SIGNALING UNIT,NIH,BETHESDA,MD 20892. RI Gutkind, J. Silvio/A-1053-2009 NR 25 TC 289 Z9 294 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 1 PY 1996 VL 271 IS 44 BP 27225 EP 27228 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VQ679 UT WOS:A1996VQ67900010 PM 8910292 ER PT J AU Varoqui, H Erickson, JD AF Varoqui, H Erickson, JD TI Active transport of acetylcholine by the human vesicular acetylcholine transporter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TORPEDO SYNAPTIC VESICLES; H-3 VESAMICOL BINDING; CLONAL CELL LINE; CHOLINE-ACETYLTRANSFERASE; CAENORHABDITIS-ELEGANS; MONOAMINE TRANSPORTER; FUNCTIONAL IDENTIFICATION; ALZHEIMERS-DISEASE; MOLECULAR-CLONING; RAT STRIATUM AB The characteristics of ATP dependent transport of acetylcholine (ACh) in homogenates of pheochromocytoma (PC-12) cells stably transfected with the human vesicular acetylcholine transporter (VAChT) cDNA are described. The human VAChT protein was abundantly expressed in this line and appeared as a diffuse band with a molecular mass of similar to 75 kDa on Western blots, Vesicular [H-3]ACh accumulation increased similar to 20 times over levels attained by the endogenous rat VAChT, expressed at low levels in control PC-12 cells, The transport of [H-3]ACh by human VAChT was dependent upon the addition of exogenous ATP at 37 degrees C. Uptake was abolished by low temperature (4 degrees C), the proton ionophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone (2.5 mu M) and bafilomycin A(1) (1 mu M), a specific inhibitor of the vesicular H+-ATPase, The kinetics of [H-3]ACh uptake by human VAChT were saturable, exhibiting an apparent K-m of 0.97 +/- 0.1 mM and V-max of 0.58 +/- 0.04 nmol/min/mg, Maximal steady-state levels of vesicular [H-3]ACh accumulation were directly proportional to the concentration of substrate present in the medium with saturation occurring at similar to 4 mM. Uptake was stereospecifically inhibited by L-vesamicol with an IC50 of 14.7 +/- 1.5 nM. The apparent affinity (K-d) of [H-3] vesamicol for human VAChT was 4.1 +/- 0.5 nM, and the B-max was 8.9 +/- 0.6 pmol/mg. The turnover (VmaxBmax) of the human VAChT was similar to 65/min. This expression system should prove useful for the structure/function analysis of VAChT. C1 NIMH,CELL BIOL LAB,MOL NEUROSCI SECT,BETHESDA,MD 20892. NR 53 TC 81 Z9 84 U1 2 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 1 PY 1996 VL 271 IS 44 BP 27229 EP 27232 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VQ679 UT WOS:A1996VQ67900011 PM 8910293 ER PT J AU Mazumder, A Neamati, N Pilon, AA Sunder, S Pommier, Y AF Mazumder, A Neamati, N Pilon, AA Sunder, S Pommier, Y TI Chemical trapping of ternary complexes of human immunodeficiency virus type I integrase, divalent metal, and DNA substrates containing an abasic site - Implications for the role of lysine 136 in DNA binding SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HIV-1 INTEGRASE; VIRAL-DNA; STABLE COMPLEX; PROTEIN; CLEAVAGE; SEQUENCE; REGION; VITRO; IDENTIFICATION; HETERODUPLEXES AB We report a novel assay for monitoring the DNA binding of human immunodeficiency virus type 1 (HIV-1) integrase and the effect of cofactors and inhibitors. The assay uses depurinated oligonucleotides that can form a Schiff base between the aldehydic abasic site and a nearby enzyme lysine epsilon-amino group which can subsequently be trapped by reduction with sodium borohydride. Chemically depurinated duplex substrates representing the U5 end of the HIV-1 DNA were initially used. We next substituted an enzymatically generated abasic site for each of 10 nucleotides normally present in a 21-mer duplex oligonucleotide representing the U5 end of the HIV-1 DNA. Using HIV-1, HIV-2, or simian immunodeficiency virus integrases, the amount of covalent enzyme-DNA complex trapped decreased as the abasic site was moved away from the conserved CA dinucleotide. The enzyme-DNA complexes formed in the presence of manganese were not reversed by subsequent addition of EDTA, indicating that the divalent metal required for integrase catalysis is tightly bound in a ternary enzyme-metal-DNA complex. Both the N- and C-terminal domains of integrase contributed to efficient DNA binding, and mutation of Lys-136 significantly reduced Schiff base formation, implicating this residue in viral DNA binding. C1 NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 47 TC 51 Z9 51 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 NOV 1 PY 1996 VL 271 IS 44 BP 27330 EP 27338 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VQ679 UT WOS:A1996VQ67900027 PM 8910309 ER PT J AU Wang, ZZ Hardy, SF Hall, ZW AF Wang, ZZ Hardy, SF Hall, ZW TI Assembly of the nicotinic acetylcholine receptor - The first transmembrane domains of truncated alpha and delta subunits are required for heterodimer formation in vivo SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSFECTED COS CELLS; ENDOPLASMIC-RETICULUM; BINDING-SITES; TERMINAL DOMAINS; EPSILON SUBUNIT; ION CHANNELS; MUSCLE-CELLS; MOUSE; PROTEIN; IDENTIFICATION AB To investigate the mechanism of assembly of the mouse muscle acetylcholine receptor, we have expressed truncated N-terminal fragments of the alpha and delta subunits in COS cells and have examined their ability to fold, to associate into heterodimers, and to form a ligand-binding site, Truncated fragments of the alpha subunit that include all, part, or none of the first transmembrane domain (M1) folded to acquire cu-bungarotoxin binding activity, Neither the full-length alpha subunit nor any of the fragments were expressed on the cell surface, although the shortest folded fragment lacking a transmembrane domain was secreted into the medium, When coexpressed with the delta subunit, the alpha subunit fragment possessing M1 formed a heterodimer containing a ligand-binding site, but shorter fragments, which lack transmembrane segments, did not associate with the delta subunit, N-terminal delta subunit fragments gave similar results. An N-terminal delta subunit fragment that contains M1 associated with the alpha subunit to form a heterodimer, while a fragment lacking M1 did not. These results show that a complete M1 domain is necessary for association of truncated N-terminal alpha and delta subunits into a heterodimer with high affinity ligand binding activity. C1 UNIV CALIF SAN FRANCISCO,DEPT PHYSIOL,SAN FRANCISCO,CA 94143. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NR 52 TC 32 Z9 32 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 NOV 1 PY 1996 VL 271 IS 44 BP 27575 EP 27584 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VQ679 UT WOS:A1996VQ67900062 PM 8910344 ER PT J AU VanMelderen, L Thi, MHD Lecchi, P Gottesman, S Couturier, M Maurizi, MR AF VanMelderen, L Thi, MHD Lecchi, P Gottesman, S Couturier, M Maurizi, MR TI ATP-dependent degradation of CcdA by Lon protease - Effects of secondary structure and heterologous subunit interactions SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; F-PLASMID; AMINO-ACID; HOST-CELL; PROTEOLYSIS; PROTEINS; DNA; SEQUENCE; LA; PURIFICATION AB CcdA, the antidote protein of the ccd post-segregational killing system carried by the F plasmid, was degraded in vitro by purified Lon protease from Escherichia coli. CcdA had a low affinity for Lon (K-m greater than or equal to 200 mu M), and the peptide bond turnover number was similar to 10 min(-1). CcdA formed tight complexes with purified CcdB, the killer protein encoded in the ccd operon, and fluorescence and hydrodynamic measurements suggested that interaction with CcdB converted CcdA to a more compact conformation. CcdB prevented CcdA degradation by Lon and blocked the ability of CcdA to activate the ATPase activity of Lon, suggesting that Lon may recognize bonding domains of proteins exposed when their partners are absent. Degradation of CcdA required ATP hydrolysis; however, CcdA41, consisting of the carboxyl-terminal 41 amino acids of CcdA and lacking the alpha-helical secondary structure present in CcdA, was degraded without ATP hydrolysis. Lon cleaved CcdA primarily between aliphatic and hydrophilic residues, and CcdA41 was cleaved at the same peptide bonds, indicating that ATP hydrolysis does not affect cleavage specificity, CcdA lost alpha-helical structure at elevated temperatures (T-m similar to 50 degrees C), and its degradation became independent of ATP hydrolysis at this temperature, ATP hydrolysis may be needed to disrupt interactions that stabilize the secondary structure of proteins allowing the disordered protein greater access to the proteolytic active sites. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. NCI,MOL BIOL LAB,BETHESDA,MD 20892. FREE UNIV BRUSSELS,DEPT BIOL MOL,GENET LAB,B-1640 RHODE ST GENESE,BELGIUM. FREE UNIV BRUSSELS,INST MOL BIOL,B-1640 RHODE ST GENESE,BELGIUM. NIDDK,ANALYT CHEM LAB,NIH,BETHESDA,MD 20892. NR 40 TC 141 Z9 142 U1 1 U2 14 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 NOV 1 PY 1996 VL 271 IS 44 BP 27730 EP 27738 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VQ679 UT WOS:A1996VQ67900084 PM 8910366 ER PT J AU Rao, GN Glasgow, WC Eling, TE Runge, MS AF Rao, GN Glasgow, WC Eling, TE Runge, MS TI Role of hydroperoxyeicosatetraenoic acids in oxidative stress-induced activating protein 1 (AP-1) activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SMOOTH-MUSCLE CELLS; LOW-DENSITY-LIPOPROTEIN; OXYGEN FREE-RADICALS; ARACHIDONIC-ACID; HYDROGEN-PEROXIDE; MESSENGER-RNA; GENE-EXPRESSION; C-FOS; GROWTH; ATHEROSCLEROSIS AB We have previously reported that hydrogen peroxide, an active oxygen species and a cellular oxidant, induces c-Fos and c-Jun mRNA expression and DNA synthesis in vascular smooth muscle cells and that these events require arachidonic acid release and metabolism through the lipoxygenase pathway. Here we have identified the eicosanoids that mediate the hydrogen peroxide-induced growth-related events in these cells. Hydrogen peroxide stimulated the production of 12- and 15-hydroperoxyeicosatetraenoic acids in vascular smooth muscle cells, Both 12- and 15-hydroperoxyeicosatetraenoic acids induced the expression of c-Fos and c-Jun protein and increased activating protein 1 (AP-1) activity, as measured by AP-1-DNA binding and AP-1-dependent human collagenase promoter-driven chloramphenicol acetyltransferase reporter gene transcription. Hydrogen peroxide and arachidonic acid also induced the expression of c-Fos and c-dun protein and AP-1 activity, Nordihydroguaiaretic acid, an inhibitor of the lipoxygenase pathway, significantly inhibited both hydrogen peroxide and arachidonic acid-stimulated c-Fos and c-Jun protein expression and AP-1 activity. Together, these findings suggest that hydrogen peroxide induces the production of eicosanoids and that the eicosanoids are potential mediators of the oxidative stress-stimulated growth-related events in vascular smooth muscle cells. C1 NIEHS,MOL BIOPHYS LAB,NIH,RES TRIANGLE PK,NC 27709. RP Rao, GN (reprint author), UNIV TEXAS,MED BRANCH,DIV CARDIOL,9138 MED RES BLDG,RT 1064,301 UNIV BLVD,GALVESTON,TX 77555, USA. NR 40 TC 66 Z9 68 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 1 PY 1996 VL 271 IS 44 BP 27760 EP 27764 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VQ679 UT WOS:A1996VQ67900088 PM 8910370 ER PT J AU Chun, RF Jeang, KT AF Chun, RF Jeang, KT TI Requirements for RNA polymerase II carboxyl-terminal domain for activated transcription of human retroviruses human T-cell lymphotropic virus I and HIV-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING PROTEINS; MAJOR LATE PROMOTER; LARGEST SUBUNIT; MAMMALIAN-CELLS; NONPHOSPHORYLATED FORM; PREINITIATION COMPLEX; TRANS-ACTIVATION; TAX PROTEIN; PHOSPHORYLATION; ENHANCER AB The carboxyl-terminal domain (CTD) of RNA polymerase (RNAP) II contains multiple repeats with a heptapeptide consensus: Tyr-Ser-Pro-Thr-Ser-Pro-Ser. It has been proposed that phosphorylation of this CTD facilitates clearance and elongation of transcription complexes initiated at the promoters. However, not all transcribed promoters require RNAP II with full-length CTD. Furthermore, different activators can promote capably the transcriptional activity of polymerase II mutants deleted in the CTD. Thus, the role of the RNAP II CTD in transcription and in response to activators remains incompletely understood. To study the role of CTD in the regulated transcription of human retroviruses human-T cell lymphotropic virus I and human immunodeficiency virus 1, we used an alpha-amanitin-resistant system developed previously (Gerber, H. P., Hagmann, M., Seipel, K., Georgiev, O., West, M. A., Litingtung, Y., Schaffner, W., and Corden, J. L. (1995) Nature 374, 660-662). We found that transcription directed by the human T-cell lymphotropic virus I activator protein Tax was strongly promoted by CTD-deficient RNA polymerase II. By contrast, the human immunodeficiency virus 1 activator Tat, which is recruited to the promoter by tethering to a nascent leader RNA, requires CTD-containing polymerase II for transcriptional activity. Biochemically, we characterized that Tat associated with a cellular CTD kinase activity, whereas Tax did not. Concordantly, we found that cellular transcription factor Sp1, which can activate CTD-deficient polymerase II with an efficiency similar to Tax, also failed to bind a CTD kinase. Taken together, these observations address mechanistic corollaries between activators with(out) a linked CTD kinase and regulated transcription by RNA polymerase II moieties with(out) a CTD. C1 NIAID,MOL VIROL SECT,MOL MICROBIOL LAB,NATL INST HLTH,BETHESDA,MD 20892. RI Jeang, Kuan-Teh/A-2424-2008; Chun, Rene/A-9415-2010 OI Chun, Rene/0000-0002-0190-0807 NR 64 TC 93 Z9 93 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 NOV 1 PY 1996 VL 271 IS 44 BP 27888 EP 27894 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VQ679 UT WOS:A1996VQ67900106 PM 8910388 ER PT J AU Kimura, T Kihara, H Bhattacharyya, S Sakamoto, H Appella, E Siraganian, RP AF Kimura, T Kihara, H Bhattacharyya, S Sakamoto, H Appella, E Siraganian, RP TI Downstream signaling molecules bind to different phosphorylated immunoreceptor tyrosine-based activation motif (ITAM) peptides of the high affinity IgE receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FC-EPSILON-RI; BASOPHILIC LEUKEMIA-CELLS; PHOSPHOTYROSINE-CONTAINING PEPTIDES; IMMUNOGLOBULIN-E RECEPTOR; T-CELL; ANTIGEN RECEPTOR; PHOSPHOLIPASE C-GAMMA-1; MAST-CELLS; ZETA-CHAIN; RBL-2H3 CELLS AB The cytoplasmic tails of both the beta and gamma subunits of the high affinity IgE receptor (Fc epsilon RI) contain a consensus sequence termed the immunoreceptor tyrosine-based activation motif (ITAM). This motif plays a critical role in receptor-mediated signal transduction. Synthetic peptides based on the ITAM sequences of the beta and gamma subunits of Fc epsilon RI were used to investigate which proteins associate with these motifs. Tyrosine-phosphorylated beta and gamma ITAM peptides immobilized on beads precipitated Syk, Lyn, Shc, Grb2, and phospholipase C-gamma 1 from lysates of rat basophilic leukemia RBL-2H3 cells. Syk was precipitated predominantly by the tyrosine-diphosphorylated gamma ITAM peptide, but much less by the diphosphorylated beta ITAM peptide or by the monophosphorylated peptides. Phospholipase C-gamma 1, Shc, and Grb2 were precipitated only by the diphosphorylated beta ITAM peptide. Non-phosphorylated ITAM peptides did not precipitate these proteins. In membrane binding assays, fusion proteins containing the Src homology 2 domains of phospholipase C-gamma 1, Shc, Syk, and Lyn directly bound the tyrosine-phosphorylated ITAM peptides. Although the ITAM sequences of the beta and gamma subunits of Fc epsilon RI are similar, once they are tyrosine-phosphorylated they preferentially bind different downstream signaling molecules. Tyrosine phosphorylation of the ITAM of the gamma subunit recruits and activates Syk, whereas the beta subunit may be important for the Ras signaling pathway. C1 NCI,CELL BIOL LAB,NATL INST HLTH,BETHESDA,MD 20892. RP Kimura, T (reprint author), NIDR,IMMUNOL LAB,NATL INST HLTH,BLDG 10,RM 1N106,BETHESDA,MD 20892, USA. RI Sakamoto, Hiroshi/A-3181-2011 NR 62 TC 56 Z9 56 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 1 PY 1996 VL 271 IS 44 BP 27962 EP 27968 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VQ679 UT WOS:A1996VQ67900117 PM 8910399 ER PT J AU Diwan, BA Rehm, S Rice, JM AF Diwan, BA Rehm, S Rice, JM TI Age- and dose-dependent transplacental carcinogenesis by N-nitrosoethylurea in Syrian golden hamsters SO JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY LA English DT Article DE NEU; age-dependent; dose-dependent; PNS tumors; melanomas ID NEUROGENIC TUMORS; RISK-FACTORS; INDUCTION; 1-ETHYL-1-NITROSOUREA; ETHYLUREA; MICE; NEUROFIBROMATOSIS; ETHYLNITROSOUREA; MODEL AB Syrian golden hamsters have a very short period (15 days) of gestation. The implantation of the blastocyst occurs on day 5, embryogenesis proceeds very rapidly thereafter and neural tube closure is completed by day 9. In the present study the effects of two different doses of N-nitrosoethylurea (NEU) administered at various stages of gestation were quantitatively evaluated in Syrian golden hamsters. NEU at either 0.2 or 0.5 mmol/kg was administered transplacentally as a single i.p. injection to pregnant hamsters on gestation days 7, 8, 9, 10, 11, 12, 13, or 14. The incidence, latency period and multiplicity of tumors varied with the dose of NEU and the stage of development at the time of NEU administration. Although tumors of the peripheral nervous system predominated, a variety of other tumors, including melanomas and visceral tumors of epithelial and mesenchymal origin, were transplacentally to NEU. Sensitivity to transplacental carcinogenesis was maximal during late gestation and very low before day 9. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RP Diwan, BA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,BIOL CARCINOGENESIS & DEV PROGRAM,BLDG 538,FREDERICK,MD 21702, USA. NR 31 TC 13 Z9 13 U1 1 U2 3 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 NOV PY 1996 VL 122 IS 11 BP 643 EP 652 DI 10.1007/BF01209026 PG 10 WC Oncology SC Oncology GA VN811 UT WOS:A1996VN81100001 PM 8898973 ER PT J AU Wang, ZZ Hardy, SF Hall, ZW AF Wang, ZZ Hardy, SF Hall, ZW TI Membrane tethering enables an extracellular domain of the acetylcholine receptor a subunit to form a heterodimeric ligand-binding site SO JOURNAL OF CELL BIOLOGY LA English DT Article ID GATED ION CHANNELS; ENDOPLASMIC-RETICULUM; ALPHA-SUBUNIT; DELTA-SUBUNIT; INFLUENZA HEMAGGLUTININ; MONOCLONAL-ANTIBODIES; TORPEDO-CALIFORNICA; TERMINAL DOMAINS; GAMMA-SUBUNIT; COS CELLS AB The first step of assembly of the nicotinic acetylcholine receptor (AChR) of adult skeletal muscle is the specific association of the alpha subunit with either delta or epsilon subunits to form a heterodimer with a ligand-binding site. Previous experiments have suggested that heterodimer formation in the ER arises from interaction between the luminal, NH2-terminal domains of the subunits. When expressed in COS cells with the delta subunit, however, the truncated NH2-terminal domain of the alpha subunit folded correctly but did not form a heterodimer. Association with the delta subunit occurred only when the NH2-terminal domain was retained in the ER and was tethered to the membrane by its own M1 transmembrane domain, by the transmembrane domain of another protein, or by a glycolipid link. In each case, the ligand-binding sites of the resulting heterodimers were indistinguishable from that formed when the full-length alpha subunit was used. Attachment to the membrane may promote interaction by concentrating or orienting the subunit; alternatively, a membrane-bound factor may facilitate subunit association. C1 NIMH,CELL BIOL LAB,NIH,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,SCH MED,DEPT PHYSIOL,SAN FRANCISCO,CA 94143. NR 61 TC 14 Z9 14 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV PY 1996 VL 135 IS 3 BP 809 EP 817 DI 10.1083/jcb.135.3.809 PG 9 WC Cell Biology SC Cell Biology GA VR268 UT WOS:A1996VR26800021 PM 8909552 ER PT J AU Slack, RS Belliveau, DJ Rosenberg, M Atwal, J Lochmuller, H Aloyz, R Haghighi, A Lach, B Seth, P Cooper, E Miller, FD AF Slack, RS Belliveau, DJ Rosenberg, M Atwal, J Lochmuller, H Aloyz, R Haghighi, A Lach, B Seth, P Cooper, E Miller, FD TI Adenovirus-mediated gene transfer of the tumor suppressor, p53, induces apoptosis in postmitotic neurons SO JOURNAL OF CELL BIOLOGY LA English DT Article ID PROGRAMMED CELL-DEATH; THYMIDINE KINASE PROMOTER; RAT SYMPATHETIC NEURONS; NERVE GROWTH-FACTOR; GATED K-CURRENTS; IN-VIVO; TRANSCRIPTIONAL ACTIVATION; BAX GENE; EXPRESSION; PROTEIN AB Programmed cell death is an ongoing process in both the developing and the mature nervous system. The tumor suppressor gene, p53, can induce apoptosis in a number of different cell types. Recently, the enhanced expression of p53 has been observed during acute neurological disease. To determine whether p53 overexpression could influence neuronal survival, we used a recombinant adenovirus vector carrying wild type p53 to transduce postmitotic neurons. A control consisting of the same adenovirus vector background but carrying the lacZ reporter expression cassette was used to establish working parameters for the effective genetic manipulation of sympathetic neurons. We have found that recombinant adenovirus can be used at titers sufficiently high (10 to 50 multiplicity of infection) to transduce the majority of the neuronal population without perturbing survival, electrophysiological function, or cytoarchitecture. Moreover, we demonstrate that overexpression of wild type p53 is sufficient to induce programmed cell death in neurons. The observation that p53 is capable of inducing apoptosis in postmitotic neurons has major implications for the mechanisms of cell death in the traumatized mature nervous system. C1 MCGILL UNIV,MONTREAL NEUROL INST,CTR NEURONAL SURVIVAL,MONTREAL,PQ H3A 2B4,CANADA. MCGILL UNIV,MONTREAL NEUROL INST,NEUROMUSCULAR RES GRP,MONTREAL,PQ H3A 2B4,CANADA. MCGILL UNIV,DEPT PHYSIOL,MONTREAL,PQ H3A 2B4,CANADA. UNIV OTTAWA,HLTH SCI CTR,DEPT PATHOL,OTTAWA,ON K1H 8M5,CANADA. NCI,MED BREAST CANC SECT,MED BRANCH,NIH,BETHESDA,MD 20892. OI Lochmuller, Hanns/0000-0003-2324-8001 NR 43 TC 99 Z9 99 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV PY 1996 VL 135 IS 4 BP 1085 EP 1096 DI 10.1083/jcb.135.4.1085 PG 12 WC Cell Biology SC Cell Biology GA VU794 UT WOS:A1996VU79400016 PM 8922388 ER PT J AU Ohtsuki, T Ruetzler, CA Tasaki, K Hallenbeck, JM AF Ohtsuki, T Ruetzler, CA Tasaki, K Hallenbeck, JM TI Interleukin-1 mediates induction of tolerance to global ischemia in gerbil hippocampal CA1 neurons SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE Mongolian gerbil; ischemic tolerance; interleukin-1 ID TUMOR-NECROSIS-FACTOR; RECEPTOR ANTAGONIST; REPERFUSION INJURY; MESSENGER-RNA; TNF-ALPHA; FOCAL ISCHEMIA; MOUSE-BRAIN; RAT-BRAIN; EXPRESSION; PRETREATMENT AB A series of experiments was performed to determine the role of interleukin (IL)-1 in the induction of tolerance to global ischemia in Mongolian gerbils. In Group I, a 2-min ''preconditioning'' ischemia protected CA1 hippocampal neurons in gerbils subjected to 3.5 min ischemia 3 days later. CA1 neuronal density was: sham, 171 +/- 3/mm; 3.5 min ischemia, 30 +/- 30/mm; 2 and 3.5 min ischemia 162 +/- 6/mm. Experiments in Group II addressed the role of IL-1 in the induction of tolerance by sublethal ischemia. Arterial IL-1 alpha and IL-1 beta became elevated between 1 and 3 days after a 2-min ischemic exposure. IL-1 alpha was: sham, 6.4 +/- 0.6 ng/ml; and 2-day, 10.2 +/- 1.2 ng/ml. IL-1 beta was: sham, 6.4 +/- 0.5 ng/ml; and 2-day, 17.3 +/- 2 ng/ml. Recombinant human IL-1 receptor antagonist (IL-1ra) i.p. blocked ischemic tolerance induction by 2-min preconditioning ischemia: 2-min ischemia + vehicle, 162 +/- 6/mm; and 2-min ischemia + IL-1ra, 67 +/- 17/mm. Experiments in Group III assessed the capacity of IL-1 to induce tolerance to brain ischemia. IL-1 alpha i.p. (0, 10, 20 mu g/kg) for 3 days prior to 3.5-min forebrain ischemia provided significant CA1 neuroprotection in a dose-dependent manner: 2 +/- 2, 68 +/- 83, and 129 +/- 42/mm, respectively. IL-1 beta (15 mu g/kg) in combination with either IL-1ra (100 mg/kg) or IL-1ra vehicle i.p. on the same schedule demonstrated a significant CA1 neuroprotection that could be nullified by IL-1ra: IL-1 beta + IL-1ra vehicle, 153 +/- 16/mm; and IL-1 beta +/- IL-1ra, 67 +/- 36/mm. Recognition that tolerance arises from stimulation of a known receptor (IL-1RI) permits molecular analysis of the intracellular signaling that is critical for production of that state. C1 NINCDS,STROKE BRANCH,NIH,BETHESDA,MD 20892. NR 38 TC 157 Z9 165 U1 1 U2 1 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 NOV PY 1996 VL 16 IS 6 BP 1137 EP 1142 PG 6 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA VP540 UT WOS:A1996VP54000007 PM 8898685 ER PT J AU Leschek, EW Doppman, JL Pass, HI Cutler, GB AF Leschek, EW Doppman, JL Pass, HI Cutler, GB TI Clinical case seminar - Localization by venous sampling of occult chorionic gonadotropin-secreting tumor in a boy with mosaic Klinefelter's syndrome and precocious puberty SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GERM-CELL TUMORS; CLEARANCE RATES C1 NCI, DEPT RADIOL, NIH, BETHESDA, MD 20892 USA. RP Leschek, EW (reprint author), NICHHD, DEV ENDOCRINOL BRANCH,NIH,BLDG 10,ROOM 10N262, 10 CTR DR, MSC 1862, BETHESDA, MD 20892 USA. NR 9 TC 2 Z9 2 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 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1996 VL 81 IS 11 BP 3825 EP 3828 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VT446 UT WOS:A1996VT44600003 PM 8923820 ER PT J AU Silver, K Walston, J Wang, YH Dowse, G Zimmet, P Shuldiner, AR AF Silver, K Walston, J Wang, YH Dowse, G Zimmet, P Shuldiner, AR TI Molecular scanning for mutations in the beta(3)-adrenergic receptor gene in nauruans with obesity and noninsulin-dependent diabetes mellitus SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID HUMAN BETA-3-ADRENERGIC RECEPTOR; GLUCOKINASE; ONSET AB We recently identified a mutation in the human beta(3)-adrenergic receptor (beta(3)AR) gene (codon 64 TGG(Trp) --> CGG(Arg); TRP64ARG) that associates with features of the insulin resistance syndrome and an earlier onset of noninsulin-dependent diabetes mellitus (NIDDM). We scanned the beta(3)AR gene for mutations by single stranded conformational polymorphism analysis in 20 Nauruans with obesity and NIDDM. No mutations were identified. Sixty-five Nauruan subjects were genotyped for the TRP64ARG beta(3)AR. All subjects were homozygous for the normal allele. We genotyped Samoans and Asians for the TRP64ARG beta(3)AR. Seven of 52 Samoans were heterozygous for the mutant arginine allele (allele frequency, 0.07). Of these, 5 were diabetic and 2 were nondiabetic (by Fisher's exact test, P = 0.4). There were trends toward increased body mass indices, waist to hip ratios, and 2-h insulin levels during oral glucose tolerance tests in Samoans with the mutation; however, the limited number of subjects available for study precluded rigorous statistical analysis. The TRP64ARG beta(3)AR was also detected in Chinese, Chinese Americans, and subjects from the Indian subcontinent. In conclusion, the TRP64ARG beta(3)AR mutation or any other mutation in the beta(3)AR gene is not a major contributor to genetic susceptibility to NIDDM and obesity likely in Nauruans. C1 JOHNS HOPKINS UNIV, SCH MED, BALTIMORE, MD 21224 USA. NIA, NIH, BALTIMORE, MD 21224 USA. INT DIABET INST, CAULFIELD, VIC, AUSTRALIA. GEN PUBL HLTH UNIT, GERALDTON, WA, AUSTRALIA. FU NIA NIH HHS [5T32-AG-00120]; NIDDK NIH HHS [1F32-DK-0934001, DK-25446] NR 22 TC 37 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 NOV PY 1996 VL 81 IS 11 BP 4155 EP 4158 DI 10.1210/jc.81.11.4155 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VT446 UT WOS:A1996VT44600059 PM 8923875 ER PT J AU Kattan, M Beck, G Boyett, J Kaplan, S Lipshultz, S Mellins, R Moodie, D Platzker, A Peavy, H Schluchter, M Shearer, W Weinstein, C Wu, M AF Kattan, M Beck, G Boyett, J Kaplan, S Lipshultz, S Mellins, R Moodie, D Platzker, A Peavy, H Schluchter, M Shearer, W Weinstein, C Wu, M TI Pediatric pulmonary and cardiovascular complications of vertically transmitted human immunodeficiency virus (P2C2 HIV) infection study: Design and methods SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE HIV; pulmonary complications; cardiovascular complications; pediatric AIDS; prospective study; vertical transmission ID PNEUMOCYSTIS-CARINII PNEUMONIA; ACQUIRED IMMUNODEFICIENCY; BIRTH-WEIGHT; CHILDREN; INFANTS; MOTHERS; MODELS; AIDS; MANIFESTATIONS; LYMPHOCYTES AB The (PC2)-C-2 HIV Study is a prospective natural history study initiated by the National Heart, Lung, and Blood Institute in order to describe the types and incidence of cardiovascular and pulmonary disorders that occur in children with vertically transmitted HIV infection (i.e., transmitted from mother to child in utero or perinatally). This article describes the study design and methods. Patients were recruited from five clinical centers in the United States. The cohort is composed of 205 infants and children enrolled after 28 days of age (Group I) and 612 fetuses and infants of HIV infected mothers, enrolled prenatally (73%) or postnatally at age <28 days (Group II). The maternal-to-infant transmission rate in Group II was 17%. The HIV-negative infants in Group II (Group IIb) serves as a control group for the HIV-infected children (Group IIa). The cohort is followed at specified intervals for clinical examination, cardiac, pulmonary, immunologic, and infectious studies and for intercurrent illnesses. In Group IIa, the cumulative loss-to-follow up rate at 3 years was 10.5%, and the 3-year cumulative mortality rate was 24.9%. The findings will be relevant to clinical and epidemiologic aspects of HIV infection in children. C1 NHLBI,BETHESDA,MD 20892. BAYLOR COLL MED,HOUSTON,TX 77030. HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. COLUMBIA UNIV,PRESBYTERIAN HOSP CITY NEW YORK,NEW YORK,NY. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. RP Kattan, M (reprint author), CUNY MT SINAI SCH MED,PEDIAT PULM & CRIT CARE DIV,POB 1202 B,1 GUSTAVE L LEVY PL,NEW YORK,NY 10029, USA. NR 33 TC 47 Z9 47 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 NOV PY 1996 VL 49 IS 11 BP 1285 EP 1294 PG 10 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA VP566 UT WOS:A1996VP56600013 ER PT J AU Letterio, JJ Geiser, AG Kulkarni, AB Dang, H Kong, LP Nakabayashi, T Mackall, CL Gress, RE Roberts, AB AF Letterio, JJ Geiser, AG Kulkarni, AB Dang, H Kong, LP Nakabayashi, T Mackall, CL Gress, RE Roberts, AB TI Autoimmunity associated with TGF-beta 1-deficiency in mice is dependent on MHC class II antigen expression SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE leukocyte; myeloid; hematopoiesis; inflammation; metaplasia ID GROWTH-FACTOR-BETA; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; INFLAMMATORY CELL INFILTRATION; MYELIN BASIC-PROTEIN; TGF-BETA; T-CELLS; MONOCLONAL-ANTIBODY; KNOCKOUT MICE; HLA-DR; C-KIT AB The progressive inflammatory process found in transforming growth factor beta 1 (TGF-beta 1>-deficient mice is associated with several manifestations of autoimmunity, including circulating antibodies to nuclear antigens, immune complex deposition, and increased expression of both class I and class II major histocompatibility complex (MHC) antigens. The contribution of MHC class II antigens to the genesis of this phenotype has been determined by crossing the TGF-beta 1-null [TGF-beta 1((-/-))] genotype into the MHC class II-deficient [MHC-II(-/-)] background, Mice homozygous for both the TGF-beta 1 null allele and the class II null allele [TGF-beta 1((-/-));MHC-II(-/-)] are without evidence of inflammatory infiltrates, circulating autoantibodies, or glomerular immune complex deposits, Instead, these animals exhibit extensive extramedullary hematopoiesis with progressive splenomegaly and adenopathy, surviving only slightly longer than TGF-beta 1((-/-));MHC-II(+/+) mice. The role of CD4(+) T cells, which are also absent in MHC class II-deficient mice, is directly demonstrated through the administration of anti-CD4 monoclonal antibodies in class II-positive, TGF-beta 1((-/-)) mice. The observed reduction in inflammation and improved survival emphasize the significance of CD4(+) cells in the pathogenesis of the autoimmune process and suggest that the additional absence of class II antigens in TGF-beta 1((-/-));MHC-II(-/-) mice may contribute to their extreme myeloid metaplasia. Thus, MHC class II antigens are essential for the expression of autoimmunity in TGF-beta 1-deficient mice, and normally may cooperate with TGF-beta 1 to regulate hematopoiesis. C1 ELI LILLY & CO,LILLY CORP CTR,LILLY RES LABS,INDIANAPOLIS,IN 46285. NIDR,GENE TARGETING RES & CORE FACIL,NIH,BETHESDA,MD 20892. UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV CLIN IMMUNOL,SAN ANTONIO,TX 78284. NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. RP Letterio, JJ (reprint author), NCI,CHEMOPREVENT LAB,NIH,BLDG 41,ROOM C629,BETHESDA,MD 20892, USA. NR 48 TC 142 Z9 148 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 NOV 1 PY 1996 VL 98 IS 9 BP 2109 EP 2119 DI 10.1172/JCI119017 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VR563 UT WOS:A1996VR56300023 PM 8903331 ER PT J AU Zhou, YF Guetta, E Yu, ZX Finkel, T Epstein, SE AF Zhou, YF Guetta, E Yu, ZX Finkel, T Epstein, SE TI Human cytomegalovirus increases modified low density lipoprotein uptake and scavenger receptor mRNA expression in vascular smooth muscle cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE atherosclerosis; transfection; reverse transcriptase polymerase chain reaction; immediate-early genes; immunohistochemistry ID VIRUS-INDUCED ATHEROSCLEROSIS; MACROPHAGE RECEPTOR; GENE-EXPRESSION; MESSENGER-RNA; INFECTION; PROTEIN; HERPESVIRUS; CHOLESTEROL; LESIONS; PHOSPHATIDYLSERINE AB Evidence suggests a possible role for human cytomegalovirus (HCMV) in the development of arteriosclerosis. One of the earliest events in plaque formation is the accumulation of lipid-laden foam cells, derived from macrophages and smooth muscle cells (SMCs), The lipid accumulation that occurs depends upon the uptake of oxidized LDL (Ox-LDL), a process in which the scavenger receptor (SR) has been postulated to play an important role, We therefore examined the effects of HCMV on this process, We demonstrate that HCMV infection of human SMCs increases modified LDL uptake and stimulates class A SR gene (SR-A) mRNA expression, In addition, infection of rat SMCs with HCMV, which causes immediate early gene expression (IE72/IE84), but no early or late HCMV gene products and no cytopathic effects, also increases SMC uptake of Ox-LDL and acetylated LDL, with either effect blocked by an excess of either cold Ox-LDL or acetylated-LDL, and by fucoidin, an SR competitor, Cotransfection of an IE72, but not an IE84, expression plasmid and a plasmid containing a Class A SR promoter/reporter gene construct enhances SR promoter activity, Since increased Ox-LDL uptake is believed to play an important role in arteriosclerosis, these results provide a link between HCMV infection and arteriosclerotic plaque formation. C1 NHLBI,CARDIOL BRANCH,NIH,BETHESDA,MD 20892. NR 55 TC 70 Z9 74 U1 0 U2 1 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 NOV 1 PY 1996 VL 98 IS 9 BP 2129 EP 2138 DI 10.1172/JCI119019 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VR563 UT WOS:A1996VR56300025 PM 8903333 ER PT J AU Kline, RL McNairn, D Holodniy, M Mole, L Margolis, D Blattner, W Quinn, TC AF Kline, RL McNairn, D Holodniy, M Mole, L Margolis, D Blattner, W Quinn, TC TI Evaluation of Chiron HIV-1/HIV-2 recombinant immunoblot assay SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID WESTERN-BLOT TESTS; INDETERMINATE; HIV-1; ANTIBODY; DONORS; PERFORMANCE; INFECTION; RISK; EIA AB In a study to determine the reliability, sensitivity, and specificity of the Chiron RIBA HIV-1/HIV-2 Strip Immunoblot Assay (RIBA HIV-1/2 SU) for confirmation of human immunodeficiency virus type 1 (HIV-1) and HIV-2. antibodies, 1,263 serum samples from various populations in the United States, Caribbean, Africa, India, and Thailand were evaluated by RIBA HIV-1/2 SIA, and the results were compared with those obtained by an HIV-1 Western blot (immunoblot) assay. All sera were tested by HIV enzyme immunoassay, RIBA HIV-1/2 SIA, and Western blotting, Samples with discrepant results were further tested by an HIV-1 and/or HIV-2 immunofluorescent-antibody assay and HIV-1 p24 antigen assay, The RIBA HIV-1/2 SIA detected all 17 HIV-1 and HIV-2 dually reactive serum samples, all 215 HIV-2-positive serum samples, and 480 of 481 HIV-1-positive serum samples for a sensitivity of 99.8%. Of 548 negative samples, 523 were RIBA HIV-1/2 SIA negative, for a specificity of 95.4%, with 22 (4%) samples interpreted as indeterminate and 3 (0.6%) interpreted as falsely positive, Western blotting detected 391 of 548 negative samples (specificity, 71.4%), with 152 (27.7%) samples interpreted as indeterminate and 5 (0.9%) interpreted as falsely positive. In conclusion, the RIBA HIV-1/2 SIA had a sensitivity comparable to that of Western blotting and could discriminate HIV-1 from HIV-2 in one blot, providing a cost advantage, Because of its high degree of specificity, the RIBA HIV-1/2 SIA further reduced the number of indeterminate results found by Western blotting, providing a more accurate means of assessing seronegative individuals. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NCI,VIRAL EPIDEMIOL SECT,BETHESDA,MD 20892. JOHNS HOPKINS UNIV HOSP,DIV INFECT DIS,BALTIMORE,MD 21287. VET AFFAIRS,PALO ALTO HLTH CARE SYST,AIDS RES CTR,PALO ALTO,CA. NR 18 TC 14 Z9 16 U1 0 U2 0 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 NOV PY 1996 VL 34 IS 11 BP 2650 EP 2653 PG 4 WC Microbiology SC Microbiology GA VM556 UT WOS:A1996VM55600003 PM 8897158 ER PT J AU YenLieberman, B Brambilla, D Jackson, B Bremer, J Coombs, R Cronin, M Herman, S Katzenstein, D Leung, S Lin, HJ Palumbo, P Rasheed, S Todd, J Vahey, M Reichelderfer, P AF YenLieberman, B Brambilla, D Jackson, B Bremer, J Coombs, R Cronin, M Herman, S Katzenstein, D Leung, S Lin, HJ Palumbo, P Rasheed, S Todd, J Vahey, M Reichelderfer, P TI Evaluation of a quality assurance program for quantitation of human immunodeficiency virus type 1 RNA in plasma by the AIDS clinical trials group virology laboratories SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; INFECTED INDIVIDUALS; COMBINATION THERAPY; DISEASE PROGRESSION; HIV-1 RNA; VIREMIA; QUANTIFICATION; SERUM; DNA; ESTABLISHMENT AB A number of quantitative assays have been developed by using amplification techniques to measure human immunodeficiency virus type 1 RNA in the plasma of infected individuals. The Virology Committee of the AIDS Clinical Trials Group in the Division of AIDS, National Institute of Allergy and Infectious Diseases, has established a quality assurance program (QAP) for quantitative assays of HIV-1 RNA levels in plasma. The primary objective of the QAP was to ascertain that a laboratory could maintain the precision required to have a 90% power to detect a fivefold difference in RNA copy number between two samples in the same batch. To achieve this goal, the QAP required an intra-assay standard deviation of no greater than 0.15 log(10) RNA copies per ml. Panels for proficiency testing consisted of coded replicate samples and a common set of standards. To date, 41 laboratories have participated in the program and have used both commercial and in-house assays. We demonstrated that 65% of the laboratories were capable of attaining the necessary level of intra-assay precision. The fitted regressions indicated that the differences among laboratories that used the same kit were generally greater than the differences among population-average regressions for the kits themselves. The use of an external QAP and a common set of standards reduced differences both among laboratories that used the same kit and among laboratories that used different kits. Thus, use of a common set of standards across clinical trial protocols would allow for cross-protocol comparisons. C1 UNIV HOSP CLEVELAND,CLEVELAND CLIN FDN,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,INST PATHOL,CLEVELAND,OH 44106. NEW ENGLAND RES INST,WATERTOWN,MA 02172. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. UNIV WASHINGTON,SEATTLE,WA 98144. ORGANON TEKNIKA CORP,DURHAM,NC 27712. ROCHE MOL SYST,BRANCHBURG,NJ 08876. STANFORD UNIV,STANFORD,CA 94305. BAYLOR COLL MED,HOUSTON,TX 77030. UNIV MED & DENT NEW JERSEY,NEWARK,NJ 07103. UNIV SO CALIF,SCH MED,LOS ANGELES,CA 90033. CHIRON CORP,EMERYVILLE,CA 94608. WALTER REED ARMY INST RES,ROCKVILLE,MD 20850. NIAID,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-25879, AI-27664, N0-AI-35172] NR 38 TC 130 Z9 132 U1 0 U2 1 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 NOV PY 1996 VL 34 IS 11 BP 2695 EP 2701 PG 7 WC Microbiology SC Microbiology GA VM556 UT WOS:A1996VM55600012 PM 8897167 ER PT J AU Saunders, N Dahler, A Jones, S Smith, R Jetten, A AF Saunders, N Dahler, A Jones, S Smith, R Jetten, A TI Interferon-gamma as a regulator of squamous differentiation SO JOURNAL OF DERMATOLOGICAL SCIENCE LA English DT Review DE keratinocyte; proliferation; differentiation; epithelial; interferon-gamma ID HUMAN EPIDERMAL-KERATINOCYTES; EPITHELIAL-CELLS; RETINOIC ACID; EXPRESSION; GENES; ACTIVATION; CORNIFIN; PROTEIN; MICE; SKIN AB Interferon-gamma (IFN-gamma) is a potent immunomodulatory molecule. Recent studies demonstrate that IFN-gamma can induce growth arrest and differentiation in epithelial cells. The signalling pathways controlling growth and differentiation in epithelial cells appears to be different to those regulating immune functions in non-epithelial cells and appear to impact on key cell cycle regulatory genes such as cdk1 and E2F1. In addition, studies with IFN-gamma have highlighted the complexity of the signalling pathways regulating the expression of differentiation markers in squamous differentiating epithelia. Given the actions of IFN-gamma upon epithelial cell growth and differentiation it should be considered a potential regulator of both immune and epithelial cell targets in various inflammatory pathologies such as psoriasis. C1 NIEHS,PULM PATHOBIOL LAB,NIH,RES TRIANGLE PK,NC 27709. RP Saunders, N (reprint author), UNIV QUEENSLAND,PRINCESS ALEXANDRA HOSP,DEPT MED,CTR IMMUNOL & CANC RES,EPITHELIAL GRP,WOOLLOONGABBA,QLD 4102,AUSTRALIA. RI saunders, nicholas/E-1544-2014; McTaggart, Jill/G-4696-2010; OI saunders, nicholas/0000-0002-2478-3420; McTaggart, Jill/0000-0002-9000-8529; Jetten, Anton/0000-0003-0954-4445 NR 23 TC 25 Z9 25 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0923-1811 J9 J DERMATOL SCI JI J. Dermatol. Sci. PD NOV PY 1996 VL 13 IS 2 BP 98 EP 106 DI 10.1016/S0923-1811(96)00535-X PG 9 WC Dermatology SC Dermatology GA VV824 UT WOS:A1996VV82400002 PM 8953408 ER PT J AU Fukase, S Sato, S Mori, K Secchi, EF Kador, PF AF Fukase, S Sato, S Mori, K Secchi, EF Kador, PF TI Polyol pathway and NADPH-dependent reductases in dog leukocytes SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article ID LENS ALDOSE REDUCTASE; POLYMORPHONUCLEAR LEUKOCYTES; DIABETES-MELLITUS; NEUTROPHIL PHAGOCYTOSIS; HEXONATE DEHYDROGENASE; ALDEHYDE REDUCTASE; INHIBITION; 3-DEOXY-3-FLUORO-D-GLUCOSE; COMPLICATIONS; CHEMOTAXIS AB Recent reports suggest that excess amounts of sugar alcohol are linked to leukocyte dysfunctions associated with diabetes. As the polyol pathway has not been firmly established in leukocytes, we have investigated NADPH-dependent reductases and sugar alcohol formation in dog leukocytes. NADPH-dependent reductase activity was observed with DL-glyceraldehyde as substrate in both mononuclear and polymorphonuclear leukocytes isolated from dog. By chromatofocusing, this activity corresponded primarily to aldehyde reductase rather than aldose reductase. The enzymatic conversion of glucose to the sugar alcohol sorbitol in leukocytes was confirmed in vitro by F-19 nuclear magnetic resonance (NMR) spectroscopy using 3-deoxy-3-fluoro-D-glucose as substrate. The NMR spectrum obtained after incubation with 10 Mm 3-deoxy-3-fluoro-D-glucose at 37 degrees C for 24 h displayed newly formed 3-deoxy-3-fluoro-D-sorbitol and 3-deoxy-3-fluoro-D-fructose peaks with both mononuclear and polymorphonuclear leukocytes. Sugar alcohol production in leukocytes from galactose-fed dogs was also observed in vivo. Galactitol accumulation was consistently observed by gas chromatography to occur in mononuclear cells while only trace amounts of galactitol were observed in polymorphonuclear leukocytes. Activation of NADPH oxidase activity in neutrophils isolated from galactose-fed dogs by zymosan was also significantly reduced compared to that of nongalactosemic control dogs. These results indicate that glucose is converted to fructose through sorbitol in both mononuclear and polymorphonuclear leukocytes despite the observations that these cells primarily contain aldehyde reductase rather than aldose reductase. In vivo, sugar alcohol accumulation in mononuclear cells is greater than in polymorphonuclear leukocytes. (C) Elsevier Science Inc., 1996. C1 NEI, LAB OCULAR THERAPEUT, NIH, BETHESDA, MD 20892 USA. NR 36 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 EI 1873-460X J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD NOV-DEC PY 1996 VL 10 IS 6 BP 304 EP 313 DI 10.1016/1056-8727(95)00065-8 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WN702 UT WOS:A1996WN70200001 PM 8972381 ER PT J AU Ando, S Nakamura, H Sasaki, S Nishiyama, K Kitahara, A Nagasawa, S Mikami, T Natsume, H Genma, R Yoshimi, T AF Ando, S Nakamura, H Sasaki, S Nishiyama, K Kitahara, A Nagasawa, S Mikami, T Natsume, H Genma, R Yoshimi, T TI Introducing a point mutation identified in a patient with pituitary resistance to thyroid hormone (Arg 338 to Trp) into other mutant thyroid hormone receptors weakens their dominant negative activities SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID GENERALIZED RESISTANCE; CO-REPRESSOR; BETA GENE; BINDING DOMAIN; RETINOIC ACID; PROTEINS AB Clinical resistance to thyroid hormone (RTH) has been classified into generalized resistance to thyroid hormone (GRTH) and pituitary resistance to thyroid hormone (PRTH) types. Since similar mutations have been identified in tri-iodothvronine T-3) receptor (TR) beta gene in GRTH and PRTH, and since considerable overlap has been seen in the clinical manifestations in patients with GRTH and PRTH, two subtypes of RTH are now considered to be a continuous spectrum with the same genetic defect. A point mutation at amino acid Arg 338 to Trp (R338W) which we identified in a patient with PRTH is very interesting, since R338W has been found in several other patients with PRTH, raising the possibility that this mutation may tend to associate with a phenotype of PRTH. In our previous study, we found that R338W had relatively less impaired transcriptional potency, weaker dominant negative activity on various T-3 response elements and poor homodimer formation, as compared with another GRTH mutant. In this study, to investigate the functional properties of R338W further, especially in terms of the relation between transcriptional activity and dimer formations, we introduced the R338W mutation into the mutant receptors, K443E and F451X, constructing the double mutants, R338W/K433E and R338W/F451X. Both R338W/K443E and R338W/F451X showed negligible T-3 binding and transcriptional activities. The dominant negative activities of K443E and F451X were, however, significantly weakened by introducing the R338W mutation. As a control, a double mutant G345R/K443E was constructed by introducing a point: mutation, G345R, located in the same exon 9 as R338W, into the K443E mutant. Dominant negative activity did not differ between G345R/K443E and K443E. Homodimer formation was significantly reduced in the double mutants containing R338W, but not G345R. In summary, introducing the R338W mutation, but not G345R, into the mutant TR significantly weakened the dominant negative activity, despite further impairment of the T-3 binding and transcriptional activities. C1 HAMAMATSU UNIV SCH MED, DEPT INTERNAL MED, DIV 2, HAMAMATSU, SHIZUOKA 43131, JAPAN. NICHHD, NIH, BETHESDA, MD 20892 USA. NR 28 TC 7 Z9 7 U1 0 U2 1 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD NOV PY 1996 VL 151 IS 2 BP 293 EP 300 DI 10.1677/joe.0.1510293 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VY164 UT WOS:A1996VY16400015 PM 8958790 ER PT J AU Roger, AJ Smith, MW Doolittle, RF Doolittle, WF AF Roger, AJ Smith, MW Doolittle, RF Doolittle, WF TI Evidence for the heterolobosea from phylogenetic analysis of genes encoding glyceraldehyde-3-phosphate dehydrogenase SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article DE Amoebae; endosymbiosis; eukaryotic evolution; lateral gene transfer; Mycetozoa; protein evolution; protist systematics; slime mould ID EUBACTERIAL ORIGIN; MOLECULAR PHYLOGENY; INTRON POSITIONS; GIARDIA-LAMBLIA; NUCLEAR GENE; EVOLUTION; SEQUENCE; EUKARYOTES; FUNGI; MITOCHONDRIA AB The phylogenetic relationships between major slime mould groups and the identification of their unicellular relatives has been a subject of controversy for many years. Traditionally, it has been assumed that two slime mould groups, the acrasids and the dictyostelids were related by Virtue of their cellular slime mould habit; a view still endorsed by at least one current classification scheme. However, a decade ago, on the basis of detailed ultrastructural resemblances, it was proposed that acrasids of the family Acrasidae were not relatives of other slime moulds but instead related to a group of mostly free-living unicellular amoebae, the Schizopyrenida. The class Heterolobosea was created to contain these organisms and has since figured in many discussions of protist evolution. We sought to test the validity of Heterolobosea by characterizing homologs of the highly conserved glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from an acrasid, Acrasis rosea; a dictyostelid, Dictyostelium discoideum; and the schizopyrenid Naegleria andersoni. Phylogenetic analysis of these and other GAPDH sequences, using maximum parsimony, neighbour-joining distance and maximum likelihood methods strongly supports the Heterolobosea hypothesis and discredits the concept of a cellular slime mould grouping. Moreover, all of our analyses place Dictyostelium discoideum as a relatively recently originating lineage, most closely related to the Metazoa, similar to other recently published phylogenies of protein-coding genes. However, GAPDH phylogenies do not show robust branching orders for most of the relationships between major groups. We propose that several of the incongruencies observed between GAPDH and other molecular phylogenies are artifacts resulting from substitutional saturation of this enzyme. C1 NCI,SCI APPLICAT INT CORP,CTR RES & DEV,FREDERICK,MD 21702. UNIV CALIF SAN DIEGO,CTR MOL GENET,SAN DIEGO,CA 92093. RP Roger, AJ (reprint author), DALHOUSIE UNIV,DEPT BIOCHEM,ROOM 8C1,SIR CHARLES TUPPER MED BLDG,HALIFAX,NS B3H 4H7,CANADA. RI Smith, Michael/B-5341-2012 NR 67 TC 33 Z9 35 U1 1 U2 3 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 NOV-DEC PY 1996 VL 43 IS 6 BP 475 EP 485 DI 10.1111/j.1550-7408.1996.tb04507.x PG 11 WC Microbiology SC Microbiology GA VY412 UT WOS:A1996VY41200007 PM 8976605 ER PT J AU Hogstrand, C Gassman, NJ Popova, B Wood, CM Walsh, PJ AF Hogstrand, C Gassman, NJ Popova, B Wood, CM Walsh, PJ TI The physiology of massive zinc accumulation in the liver of female squirrelfish and its relationship to reproduction SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE squirrelfish; Holocentrus marianus; zinc accumulation; zinc; metallothionein; FZnBP; physiology; reproduction; fish; pisces ID TROUT SALMO-GAIRDNERI; RAINBOW-TROUT; RAT HEPATOCYTES; METALLOTHIONEIN; VITELLOGENIN; LOCALIZATION; INDUCTION; PROTEINS; COPPER; CHROMATOGRAPHY AB It is well known that zinc is an essential micronutrient and, as a rule, organisms keep relatively constant low levels of zinc to maintain cellular functions. The squirrelfish family (Holocentridae) is the only known exception from this rule. Squirrelfish accumulate very high concentrations of zinc in the liver. In the present study, we demonstrate that, while female squirrelfish store large amounts of zinc in the liver and ovaries, the males show zinc levels that are typical for vertebrates. The zinc content of the diet is the same in males and females, and zinc is not lost from the liver during starvation. Thus, the difference between genders in zinc storage is not dependent upon the diet. Rather, there are at least two processes that contribute to the accumulation in females. First, females possess high levels of two major zinc-binding proteins: metallothionein (MT) and a novel female-specific zinc-binding protein (FZnBP). In females, but not in males, almost all MT is present in the hepatocyte nucleus, FZnBP is exclusively found in the hepatocyte cytosol of females. Second, hepatocytes of female squirrelfish have a high capacity to transport zinc across the plasma membrane. In addition to the liver, only the gonads of females showed unusually high concentrations of zinc. Administration of exogenous oestrogen to females decreases the hepatic zinc concentration while there is a matching increase in the zinc content of the ovaries. Thus, oestrogen may trigger a redistribution of zinc from liver to ovaries. Together, our findings suggest that female squirrelfish may be uniquely adapted to detoxify zinc and to utilize it as a macronutrient for processes related to reproduction. C1 UNIV MIAMI,ROSENSTIEL SCH MARINE & ATMOSPHER SCI,NIEHS,MARINE & FRESHWATER BIOMED SCI CTR,MIAMI,FL 33149. UNIV KENTUCKY,TH MORGAN SCH BIOL SCI,LEXINGTON,KY 40506. MCMASTER UNIV,DEPT BIOL,HAMILTON,ON L8S 4K1,CANADA. RP Hogstrand, C (reprint author), UNIV MIAMI,ROSENSTIEL SCH MARINE & ATMOSPHER SCI,DIV MARINE BIOL & FISHERIES,MIAMI,FL 33149, USA. RI Hogstrand, Christer/C-9041-2013 FU NIEHS NIH HHS [ES-05705] NR 39 TC 22 Z9 24 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD NOV PY 1996 VL 199 IS 11 BP 2543 EP 2554 PG 12 WC Biology SC Life Sciences & Biomedicine - Other Topics GA VR637 UT WOS:A1996VR63700020 PM 9114505 ER PT J AU Morawetz, RA Gabriele, L Rizzo, LV NobenTrauth, N Kuhn, R Rajewsky, K Muller, W Doherty, TM Finkelman, F Coffman, RL Morse, HC AF Morawetz, RA Gabriele, L Rizzo, LV NobenTrauth, N Kuhn, R Rajewsky, K Muller, W Doherty, TM Finkelman, F Coffman, RL Morse, HC TI Interleukin (IL)-4-independent immunoglobulin class switch to immunoglobulin (Ig)E in the mouse SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID RETROVIRUS-INDUCED IMMUNODEFICIENCY; INVIVO IGE RESPONSES; MURINE IMMUNE-SYSTEM; STIMULATORY FACTOR-I; T-CELL CLONES; HUMAN B-CELLS; GENE-EXPRESSION; MONOCLONAL-ANTIBODIES; POLYCLONAL ACTIVATION; DEFICIENT MICE AB Immunoglobulin (Ig) class switching in B cells is regulated by stimuli transduced by cytokines and cell-cell contact. Among these stimuli, interleukin (IL)-4 has been considered an absolute prerequisite for class switching to ISE in the mouse. Here we report that IL-4-deficient (IL-4(-/-)) and wild-type mice had comparably elevated serum IgE levels during the course of a murine retrovirus-induced immunodeficiency syndrome, MAIDS. IgE switching in IL-4(-/-) mice was also induced by injection of anti-IgD antibody. Treatment with anti-IgD induced germline epsilon (g epsilon) transcripts with comparable efficiency in IL-4(-/-) mice and controls, but the levels of productive epsilon transcripts (p epsilon) were lower by a factor of 200 and serum IgE levels were lower by a factor of 300 in IL-4(-/-) mice Bs compared with controls. Induction of g epsilon after anti-IgD treatment of IL-4(-/-) mice was unaffected by simultaneous treatment with monoclonal antibodies to IL-4 and IL-4 receptor ol chain; Infection of IL-4(-/-) mice with Nippostrongylus brasiliensis, a potent stimulus for IgE production, resulted in induction of g epsilon transcripts; however, p epsilon transcripts were barely detectable and serum IgE was not detected. These findings establish a novel IL-4-independent pathway for IgE switching in the mouse that is strongly activated in retroviral infection but weakly in nematode infection. This pathway appears to be dependent on distinct factors that separately control induction of g epsilon transcription and switch recombination to p epsilon. C1 NEI,NIH,BETHESDA,MD 20892. DNAX RES INST MOL & CELLULAR BIOL INC,DEPT IMMUNOL,PALO ALTO,CA 94304. UNIV COLOGNE,INST GENET,D-50923 COLOGNE,GERMANY. UNIV CINCINNATI,COLL MED,CINCINNATI,OH 45267. JACKSON LAB,BAR HARBOR,ME 04609. RP Morawetz, RA (reprint author), NIAID,IMMUNOPATHOL LAB,NIH,BLDG 7,ROOM 308,7 CTR DR MSC 0760,BETHESDA,MD 20892, USA. RI Rizzo, Luiz Vicente/B-4458-2009; Muller, Werner/B-9044-2008; OI Muller, Werner/0000-0002-1297-9725; Morse, Herbert/0000-0002-9331-3705 FU NIAID NIH HHS [N01-AI-45203] NR 58 TC 62 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 NOV 1 PY 1996 VL 184 IS 5 BP 1651 EP 1661 DI 10.1084/jem.184.5.1651 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VT694 UT WOS:A1996VT69400007 PM 8920855 ER PT J AU Ota, Y Beitz, LO Scharenberg, AM Donovan, JA Kinet, JP Samelson, LE AF Ota, Y Beitz, LO Scharenberg, AM Donovan, JA Kinet, JP Samelson, LE TI Characterization of Cbl tyrosine phosphorylation and a Cbl-Syk complex in RBL-2H3 cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HIGH-AFFINITY RECEPTOR; PROTOONCOGENE C-CBL; ANTIGEN RECEPTOR; PROTEIN PRODUCT; SIGNAL-TRANSDUCTION; V-CBL; PHOSPHATIDYLINOSITOL 3-KINASE; IMMUNOGLOBULIN-E; EGF STIMULATION; JURKAT CELLS AB Tyrosine phosphorylation of the Cbl protooncogene has been shown to occur after engagement of a number of different receptors on hematopoietic cells. However, the mechanisms by which these receptors induce Cbl tyrosine phosphorylation are poorly understood. Here we demonstrate that engagement of the high affinity IgE receptor (Fc epsilon R1) leads to the tyrosine phosphorylation of Cbl and analyze how this occurs. We show that at least part of Fc epsilon RI-induced Cbl tyrosine phosphorylation is mediated by the Syk tyrosine kinase, and that the Syk-dependent tyrosine phosphorylation of Cbl occurs mainly distal to the Cbl proline-rich region within the COOH-terminal 250 amino acids. Furthermore, we show by coprecipitation that Cbl is present in a complex with Syk before receptor engagement, that the proline-rich region of Cbl and a region of Syk comprised of the two SH2 domains and intradomain linker are required for formation of the complex, and that little. or no tyrosine-phosphorylated Cbl is detected in complex with Syk. Overexpression of truncation mutants of Cbl capable of binding Syk has the effect of blocking tyrosine phosphorylation of endogenous Cbl. These results define a potentially important intramolecular interaction in mast cells and suggest a complex function for Cbl in intracellular signaling pathways. C1 NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892. BETH ISRAEL HOSP,LAB ALLERGY & IMMUNOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. NR 54 TC 83 Z9 83 U1 0 U2 2 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 NOV 1 PY 1996 VL 184 IS 5 BP 1713 EP 1723 DI 10.1084/jem.184.5.1713 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VT694 UT WOS:A1996VT69400012 PM 8920860 ER PT J AU Flamand, V Shores, EW Tran, T Huang, K Lee, E Grinberg, A Kinet, JP Love, PE AF Flamand, V Shores, EW Tran, T Huang, K Lee, E Grinberg, A Kinet, JP Love, PE TI Delayed maturation of CD4(-)CD8(-) Fc gamma RII/III+ T and natural killer cell precursors in Fc epsilon RI gamma transgenic mice SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ANTIGEN RECEPTOR COMPLEX; HIGH-AFFINITY RECEPTOR; LYMPHOCYTES-T; IGE RECEPTOR; ZETA-CHAIN; SUBUNIT; EXPRESSION; GENE; THYMOCYTES; ASSOCIATION AB Fc epsilon RI gamma (gamma) is a member of a group of related proteins (the zeta-family dimers) that function as signal-transducing components of both Fc receptors and the T cell antigen receptor (TCR). Analysis of gamma expression during fetal thymus ontogeny revealed that it is expressed in early thymocytes, before the initiation of clonotypic TCR-alpha and TCR-beta gene rearrangement but is down-regulated in most adult thymocytes. To explore a possible role for gamma in thymocyte development, we generated transgenic mice in which this protein was overexpressed at all stages of ontogeny. Overexpression of gamma inhibited the maturation of T cells as well as natural killer (NK) cells. The developmental effects were transgene dose related and correlated with markedly delayed maturation of fetal CD4(-)CD8(-) FcRII/III+ thymocytes, cells thought to include the progenitors of both T and NK cells. These results suggest that the zeta and gamma chains serve distinctive functions in thymocyte development and indicate that Fc receptor(s) may play an important role in regulating the differentiation of early progenitor cells within the thymus. C1 NICHHD,LAB MAMMALIAN GENES & DEV,NIH,BETHESDA,MD 20892. NIAID,LAB MOL ALLERGY & IMMUNOL,NIH,ROCKVILLE,MD 20852. US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. NR 35 TC 20 Z9 20 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 NOV 1 PY 1996 VL 184 IS 5 BP 1725 EP 1735 DI 10.1084/jem.184.5.1725 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VT694 UT WOS:A1996VT69400013 PM 8920861 ER PT J AU Katz, JF Stebbins, C Appella, E Sant, AJ AF Katz, JF Stebbins, C Appella, E Sant, AJ TI Invariant chain and DM edit self-peptide presentation by major histocompatibility complex (MHC) class II molecules SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HLA-DR MOLECULES; ANTIGEN-PROCESSING MUTANT; INTRACELLULAR-TRANSPORT; RESTRICTED PRESENTATION; PRESENTATION PATHWAYS; BETA DIMERS; GENES; CELLS; PROTEIN; COMPARTMENTS AB We have studied the consequences of invariant chain (Ii) and DM expression on major histocompatibility complex (MHC) class II function. Ii has a number of discrete functions in the biology of class II, including competitive blocking of peptide binding in the endoplasmic reticulum and enhancing localization in the endocytic compartments. DM is thought to act primarily in endosomes to promote dissociation of the Ii-derived (CLIP) peptide from the class II antigen-binding pocket and subsequent peptide loading. In this study, we have evaluated the functional role of Ii and DM by examining their impact on surface expression of epitopes recognized by a large panel of alloreactive T cells. We find most epitopes studied are influenced by both Ii and DM. Most strikingly, we. find that surface expression of a significant fraction of peptide-class II complexes is extinguished, rather than enhanced, by DM expression within the APC. The epitopes antagonized by DM do not appear to be specific for CLIP. Finally, we found that DM. was also able to extinguish recognition of a defined peptide derived hom the internally synthesized H-2L(d) protein. Thus, rather than primarily serving in the removal of CLIP, DM may have a more generalized function of editing the array of peptides that are presented by class II. This editing can be either positive or negative, suggesting that DM plays a specifying role in the display of peptides presented to CD4 T cells. C1 UNIV CHICAGO,DEPT PATHOL,COMM IMMUNOL,CHICAGO,IL 60637. NCI,NIH,BETHESDA,MD 20892. NR 44 TC 93 Z9 93 U1 0 U2 2 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 NOV 1 PY 1996 VL 184 IS 5 BP 1747 EP 1753 DI 10.1084/jem.184.5.1747 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VT694 UT WOS:A1996VT69400015 PM 8920863 ER PT J AU Candeias, S Muegge, K Durum, SK AF Candeias, S Muegge, K Durum, SK TI Junctional diversity in signal joints from T cell receptor beta and delta loci via terminal deoxynucleotidyl transferase and exonucleolytic activity SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID BROKEN DNA-MOLECULES; V(D)J RECOMBINATION; GENE REARRANGEMENTS; EXCISION PRODUCTS; NUCLEOTIDE INSERTIONS; CODING JOINTS; THYMOCYTES; SEQUENCE; RESOLUTION; INVERSION AB The site-specific V(D)J recombination reaction necessary to assemble the genes coding for immunoglobulin (Ig) and T cell receptor (TCR) variable regions is initiated by a precise double strand cut at the border of the recombination signals nanking the genes. Extensive processing of the coding ends before their Ligation accounts for most of the Ig and TCR repertoire diversity. This processing includes both base additions to and loss from the coding ends. On the other hand, it has generally been thought that signal ends are not modified before they an fused, and that signal joints consist of a perfect head-to-head ligation of the recombination signals. In this study, we analyzed signal joints created during the rearrangement of different TCR-beta and TCR-delta genes in thymocytes. We show that a significant fraction (up to 24%) of these signal joints exhibits junctional diversity. This diversity results from N nucleotide additions for TCR-beta signal joints, and from N additions and exonucleolytic digestion for TCR-delta joints. Altogether, our findings suggest that: (a) signal ends can undergo some of the same modifications as coding ends, (b) inversional rearrangement generates more diversity than deletional events, and (c) fine differences exist in the recombinase/DNA complexes formed at each rearranging locus. C1 NCI,MOL IMMUNOREGULAT LAB,FREDERICK,MD 21702. RP Candeias, S (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,BLDG 560,FREDERICK,MD 21702, USA. NR 33 TC 20 Z9 22 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 NOV 1 PY 1996 VL 184 IS 5 BP 1919 EP 1926 DI 10.1084/jem.184.5.1919 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VT694 UT WOS:A1996VT69400031 PM 8920879 ER PT J AU Zhong, GM Castellino, F Romagnoli, P Germain, RN AF Zhong, GM Castellino, F Romagnoli, P Germain, RN TI Evidence that binding site occupancy is necessary and sufficient for effective major histocompatibility complex (MHC) class II transport through the secretory pathway redefines the primary function of class II-associated invariant chain peptides (CLIP) SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID SURFACE EXPRESSION; T-CELL; INTRACELLULAR-TRANSPORT; MICE LACKING; BETA DIMERS; IN-VITRO; HLA-DR; MOLECULES; PROTEINS; DM AB Invariant chain (Ii) associates with newly synthesized class II molecules in the endoplasmic reticulum (ER), an interaction that has been shown to interfere with peptide binding to class II molecules. The class II-associated invariant chain peptide (CLIP) region (residues 81-104) of Ii is believed to mediate this inhibition by engaging the binding domain of class II Like an antigenic peptide. Together, these findings have given rise to a model in which CLIP association with the class II groove acts to prevent inappropriate presentation of peptides imported into the ER for association with major histocompatibility complex class I molecules. However, the properties of class II molecules synthesized by cells lacking coexpressed Ii are at least superficially inconsistent with this paradigm in that they do not show clear evidence of peptide acquisition. At the same time, we have previously shown the shortest form of Ii still containing CLIP to play an essential role in regulation of early class II molecule assembly and transport in the secretory pathway. Using covalent peptide technology, we now show that occupancy of the class II binding site in the ER regulates class II trafficking to the Golgi complex, an event that is the locus of the major defect in cells of Ii-deficient mice. These data argue that CLIP occupies the class II binding site, not to prevent interaction with short peptides meant for class I, but rather to maintain the structural integrity of class II molecules that are labile without engaged binding regions, and that would also associate with intact proteins in the ER if left unoccupied. By these means, CLIP occupancy of the class II binding site promotes effective export of useful class II molecules for endocytic peptide acquisition. C1 NIAID,LYMPHOCYTE BIOL SECT,IMMUNOL LAB,NIH,BETHESDA,MD 20892. RI Romagnoli, Paola/K-2237-2014 NR 40 TC 71 Z9 71 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 NOV 1 PY 1996 VL 184 IS 5 BP 2061 EP 2066 DI 10.1084/jem.184.5.2061 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VT694 UT WOS:A1996VT69400048 PM 8920896 ER PT J AU Li, MF Muller, J Rao, V Hearing, V Lueders, K Gorelik, E AF Li, MF Muller, J Rao, V Hearing, V Lueders, K Gorelik, E TI Loss of intracisternal A-type retroviral particles in BL6 melanoma cells transfected with MHC class I genes SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID TNF-MEDIATED CYTOTOXICITY; INCREASED SENSITIVITY; PROVIRAL ELEMENTS; BINDING SITES; H-2K(B) GENE; H-2 GENES; EXPRESSION; MOUSE; ANTIGEN; LYMPHOCYTES AB Electron microscopy of B16 melanoma and its sublines revealed that these cells produce numerous intracisternal A-type retroviral particles (IAPs). To identify and sequence the melanoma-associated IAPs of C57BL/6 mice, a cDNA library was constructed from IAP-producing BL6-8 cell RNA and screened using MIA14 IAP DNA as a probe. A 6 . 8 kb mRNA was identified that represents the full-length message for a new subfamily of IAP, termed MeIAP. The melanoma-derived IAP cDNA showed high similarity to MIA14 with major differences in the LTR. A nine base motif of the R region showed that this IAP differs from other previously sequenced IAPs. Analysis of the individual clones from BL6 melanoma revealed that IAPs were produced only in the clones that failed to express H-2K(b) molecules. No IAPs were found in the melanoma clones that expressed endogenous H-2K(b). To analyse further the association between MHC class I genes and IAP production, the H-2K(b)-negative clones of BL6 melanoma were transfected with various H-2 genes. Transfection of the H-2K(b) or H-2K(d), but not H-2D(d) or H-2L(d) genes resulted in the elimination of IAPs. Northern blot analysis revealed that loss of IAPs in the H-2K gene-transfected BL6 melanoma cells was due to lack of IAP transcripts. Elimination of IAPs in the H-2K(b)-positive BL6 melanoma cells was also accompanied by alterations in expression of various cellular genes and changes of their phenotypic properties. C1 UNIV PITTSBURGH,PITTSBURGH CANC INST,PITTSBURGH,PA 15213. UNIV PITTSBURGH,DEPT PATHOL,PITTSBURGH,PA 15213. US FDA,DIV VIRAL PROD,BETHESDA,MD 20892. NCI,NIH,CELL BIOL LAB,BETHESDA,MD 20892. NCI,NIH,BIOCHEM LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA-59903] NR 37 TC 10 Z9 10 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD NOV PY 1996 VL 77 BP 2757 EP 2765 DI 10.1099/0022-1317-77-11-2757 PN 11 PG 9 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA VT286 UT WOS:A1996VT28600010 PM 8922469 ER PT J AU Moreno, MB Memon, SA Zacharchuk, CM AF Moreno, MB Memon, SA Zacharchuk, CM TI Apoptosis signaling pathways in normal T cells differential activity of Bcl-2 and IL-1 beta-converting enzyme family protease inhibitors on glucocorticoid- and Fas-mediated cytotoxicity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ACTIVATION-INDUCED APOPTOSIS; TUMOR-NECROSIS-FACTOR; ICE/CED-3 PROTEASE; GLIOMA-CELLS; IN-VIVO; DEATH; ANTIBODY; EXPRESSION; SURVIVAL; BCL-X(L) AB Fas-mediated apoptosis plays an important role in regulating the immune response in peripheral T cells. Restimulation of T cell blasts up-regulates Fas and Fas ligand expression, with subsequent interaction leading to cell death. Overexpression of Bcl-2 in tumor cells blocks apoptosis induced by many stimuli, but inhibition of Fas-mediated killing has not been consistently observed. To examine the behavior of Bcl-2 in normal cells, T cell blasts were transiently transfected with Bcl-2 and related gene products to determine the effect on apoptotic signaling. Transient overexpression of Bcl-2 in mouse and human T cell blasts did not block Fas-mediated apoptosis, whereas etoposide- and glucocorticoid-induced cytotoxicity was potently inhibited, Expression of Bcl-x(L) and adenovirus E1B 19K did not interfere with anti-fas killing. In contrast, interleukin-1 beta-converting enzyme family protease inhibitors Ac-DEVD-CHO and CrmA blocked Fas-mediated apoptosis. These results suggest that peripheral T cells use distinct apoptosis signaling pathways with differential sensitivity to Bcl-2 and interleukin-1 beta-converting enzyme family protease inhibitors. Since T cells normally express Bcl-2 and Bcl-x(L) following activation, their inability to block Fas-mediated apoptosis may allow for the elimination of self-reactive cells and the appropriate regulation of immune responses. C1 NCI,LAB IMMUNE CELL BIOL,DIV BASIC SCI,NIH,BETHESDA,MD 20892. RI Memon, Sarfraz/E-1198-2013 NR 55 TC 49 Z9 51 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1996 VL 157 IS 9 BP 3845 EP 3849 PG 5 WC Immunology SC Immunology GA VP227 UT WOS:A1996VP22700011 PM 8892614 ER PT J AU SchartonKersten, TM Wynn, TA Denkers, EY Bala, S Grunvald, E Hieny, S Gazzinelli, RT Sher, A AF SchartonKersten, TM Wynn, TA Denkers, EY Bala, S Grunvald, E Hieny, S Gazzinelli, RT Sher, A TI In the absence of endogenous IFN-gamma, mice develop unimpaired IL-12 responses to Toxoplasma gondii while failing to control acute infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; NECROSIS-FACTOR-ALPHA; INTERFERON-GAMMA; LEISHMANIA-MAJOR; INTERLEUKIN-12 PRODUCTION; LISTERIA-MONOCYTOGENES; NITRIC-OXIDE; IN-VIVO; RESISTANCE; INDUCTION AB The relationship between IFN-gamma and IL-12 in generating innate immune responses and resistance to acute Toxoplasma gondii infection was assessed in T. gondii-exposed lFN-gamma knockout (gko) mice. Gko mice, in contrast to wild-type (wt) animals, rapidly succumbed to infection with either the avirulent ME49 strain or, surprisingly, an attenuated temperature-sensitive mutant strain, ts4. Microscopic examination of peritoneal exudates from infected gko mice demonstrated that mortality is associated with unchecked tachyzoite replication. Nevertheless, both wt and gko animals developed a peritoneal inflammatory response that in gko animals was greater due to a 5- to 10-fold increase in the number of granulocytes recruited to the site of infection. In addition, IL-12 production in gko mice was both unimpaired and functional since a significant, albeit lower than wt, IL-12-dependent NK cell response developed in these animals. Regardless, no evidence for an IFN-gamma-independent protective function for IL-12 or NK cells was apparent since in vivo treatment of gko mice with an IL-12-neutralizing mAb ablated the NK cell response, but did not decrease survival. Together, these data identify distinct functions for IL-12 and IFN-gamma in host resistance to T. gondii: IL-12 precedes and initiates synthesis of IFN-gamma, while the latter lymphokine directly controls parasite growth and diminishes the contribution of IL-4- and IL-5-producing T cell subsets. C1 US FDA, DIV ANTIVIRAL DRUG PROD, ROCKVILLE, MD 20857 USA. UNIV FED MINAS GERAIS, DEPT BIOCHEM & IMMUNOL, BELO HORIZONTE, MG, BRAZIL. RP SchartonKersten, TM (reprint author), NIAID, PARASIT DIS LAB,IMMUNOBIOL SECT,NIH,BLDG 4, ROOM 132, BETHESDA, MD 20892 USA. RI Wynn, Thomas/C-2797-2011 NR 56 TC 199 Z9 201 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1996 VL 157 IS 9 BP 4045 EP 4054 PG 10 WC Immunology SC Immunology GA VP227 UT WOS:A1996VP22700035 PM 8892638 ER PT J AU Wynn, TA Reynolds, A James, S Cheever, AW Caspar, P Hieny, S Jankovic, D Strand, M Sher, A AF Wynn, TA Reynolds, A James, S Cheever, AW Caspar, P Hieny, S Jankovic, D Strand, M Sher, A TI IL-12 enhances vaccine-induced immunity to schistosomes by augmenting both humoral and cell-mediated immune responses against the parasite SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RADIATION-ATTENUATED CERCARIAE; CD4+ T-CELLS; INTERFERON-GAMMA PRODUCTION; CYTOKINE GENE-EXPRESSION; PROTECTIVE IMMUNITY; IFN-GAMMA; IRRADIATED CERCARIAE; LEISHMANIA-MAJOR; LISTERIA-MONOCYTOGENES; MANSONI SCHISTOSOMULA AB The production of Th1-type cytokines is associated with:strong cell-mediated immunity, while Th2-type cytokines typically dominate humoral immune responses. In mice vaccinated a single time with attenuated cercariae of Schistosoma mansoni, the protection induced is associated with Th1 cytokine-dependent, cell-mediated immunity. In contrast, mice vaccinated multiple times display a more Th2-type dominant cytokine response and develop Ab-dependent resistance. We have previously shown that IL-12 enhances cell-mediated immunity in singly vaccinated mice, In the present study, we asked what effects administering IL-12 as an adjuvant would have on the development of a protective humoral response in multiply immunized animals. We found that multiply immunized/lL-12-treated mice displayed a marked increase in resistance to challenge infection, with some animals demonstrating complete protection. The IL-12-vaccinated mice developed strongly polarized Th1 responses but, importantly, also showed significant increases In parasite-specific Ab and, in particular, IgG2a, IgG26, and IgG1 isotypes. Passive transfer demonstrated an enhanced ability of serum from these animals to protect naive recipients. In addition, animals vaccinated in the presence of IL-12 also developed macrophages with increased nitric oxide-dependent killing activity against the parasites. Together, these data demonstrate that IL-12, initially described as an adjuvant for cell-mediated immunity, may be used to simultaneously to promote both humoral and cell-mediated protective responses against infection. C1 JOHNS HOPKINS UNIV,DEPT PHARMACOL & MOL SCI,BALTIMORE,MD 21205. RP Wynn, TA (reprint author), NIAID,PARASIT DIS LAB,IMMUNOBIOL SECT,NIH,BLDG 4,ROOM 126,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Wynn, Thomas/C-2797-2011 NR 73 TC 97 Z9 103 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1996 VL 157 IS 9 BP 4068 EP 4078 PG 11 WC Immunology SC Immunology GA VP227 UT WOS:A1996VP22700038 PM 8892641 ER PT J AU Baumgartner, RA Deramo, VA Beaven, MA AF Baumgartner, RA Deramo, VA Beaven, MA TI Constitutive and inducible mechanisms for synthesis and release of cytokines in immune cell lines SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; PROTEIN-KINASE-C; BASOPHILIC RBL-2H3 CELLS; NECROSIS-FACTOR-ALPHA; GENE-EXPRESSION; HISTAMINE-RELEASE; 2H3 CELLS; TGF-BETA; T-CELL; GLUCOCORTICOIDS AB We found that production and release of two functionally antagonistic cytokines, TGF-alpha and TNF-alpha, were regulated differently in the mast cell, T cell, and macrophage cell lines REL-2H3, MLA-144, and U-937, respectively. TGF-alpha was produced and released constitutively in all three cell lines. When, however, the cell lines were stimulated with Ag, LPS, or calcium ionophore plus PMA, acceleration of release and some additional production of TGF-beta were apparent. In contrast, TNF-alpha was produced and released only when these lines were stimulated. Although neither the glucocorticoid, dexamethasone, nor the protein kinase C inhibitor, Ro31-7549, suppressed constitutive production or release of TGF-beta, these agents inhibited TNF-alpha production and the inducible component of TGF-beta production noted above. The release of these cytokines, whether constitutive or inducible, was dependent on Golgi-processing as indicated by inhibition with brefeldin A. Therefore, although both types of cytokines were processed by Golgi, only TNF-alpha and the inducible component of TGF-beta production were protein kinase C or steroid-regulated processes. These findings suggested that constitutive and inducible pathways exist for production and release of cytokines and that the inducible pathways can be selectively suppressed by pharmacologic agents. RP Baumgartner, RA (reprint author), NHLBI,MOL IMMUNOL LAB,NIH,BLDG 10,ROOM 8N109,BETHESDA,MD 20892, USA. NR 31 TC 41 Z9 42 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 NOV 1 PY 1996 VL 157 IS 9 BP 4087 EP 4093 PG 7 WC Immunology SC Immunology GA VP227 UT WOS:A1996VP22700040 PM 8892643 ER PT J AU Song, WC Deng, CJ Raszmann, K Moore, R Newbold, R McLachlan, JA Negishi, M AF Song, WC Deng, CJ Raszmann, K Moore, R Newbold, R McLachlan, JA Negishi, M TI Mouse decay-accelerating factor - Selective and tissue-specific induction by estrogen of the gene encoding the glycosylphosphatidylinositol-anchored form SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MEMBRANE COFACTOR PROTEIN; COMPLEMENT REGULATORY PROTEIN; TYROSINE KINASES; FACTOR CD55; FACTOR DAF; HUMAN CR-1; RECEPTOR; EXPRESSION; CLONING; FAMILY AB Neonatal exposure of mice to estrogen (diethylstilbestrol) results in a high incidence (90%) of uterine tumor later in life. In an effort to screen for estrogen-regulated genes in the uterus of the neonatal mouse, we have isolated a murine homologue of the human decay-accelerating factor (DAF), a glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein and a member of the regulators of complement activation family of proteins that function to prevent autologous complement-mediated tissue damage. The induced mouse DAF cDNA has a 64% sequence identity with the human counterpart at the nucleotide level and a 50% identity in the deduced amino acid sequence, It consists of 390 amino acids and contains four short consensus repeats of internal homology characteristic of human DAF, It. also contains a hydrophobic C-terminal that most likely serves as a signal for GPI anchor attachment. Sequence comparison with the recently reported mouse DAF cDNAs confirmed that the estrogen-inducible gene corresponds to the mouse GPI DAF gene. The induction of mouse DAF by estrogen is tissue specific and can be mimicked by the antiestrogen tamoxifen, Furthermore, the, regulation of uterine DAF expression by estrogen is limited to the GPI DAF gene, The transmembrane DAF gene is not expressed in the mouse uterus, either with or without estrogen stimulation, These results suggest that the two mouse DAF genes are differentially regulated, and that the GPI-anchored DAF may play important roles in estrogen responses and other physiologic or pathophysiologic processes of the female reproductive system. C1 UNIV PENN,SCH MED,DEPT PHARMACOL,PHILADELPHIA,PA 19104. NIEHS,PHARMACOGENET SECT,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. NIEHS,REPROD TOXICOL GRP,TOXICOL BRANCH,RES TRIANGLE PK,NC 27709. RP Song, WC (reprint author), UNIV PENN,SCH MED,CTR EXPT THERAPEUT,PHILADELPHIA,PA 19104, USA. NR 37 TC 49 Z9 49 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 NOV 1 PY 1996 VL 157 IS 9 BP 4166 EP 4172 PG 7 WC Immunology SC Immunology GA VP227 UT WOS:A1996VP22700051 PM 8892654 ER PT J AU Wideroff, L Schiffman, MH Hoover, R Tarone, RE Nonnenmacher, B Hubbert, N Kirnbauer, R Greer, CE Lorincz, AT Manos, MM Glass, AG Scott, DR Sherman, ME Buckland, J Lowy, D Schiller, J AF Wideroff, L Schiffman, MH Hoover, R Tarone, RE Nonnenmacher, B Hubbert, N Kirnbauer, R Greer, CE Lorincz, AT Manos, MM Glass, AG Scott, DR Sherman, ME Buckland, J Lowy, D Schiller, J TI Epidemiologic determinants of seroreactivity to human papillomavirus (HPV) type 16 virus-like particles in cervical HPV-16 DNA-positive and -negative women SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID INTRAEPITHELIAL NEOPLASIA; GLUCOCORTICOID HORMONES; ORAL-CONTRACEPTIVES; CARCINOMA CELLS; TRANSCRIPTION; PROGESTERONE; EXPRESSION; INFECTION AB The epidemiologic determinants of seroreactivity to human papillomavirus (HPV) type 16 L1/L2 virus-like particles (VLPs) were assessed separately in HPV-16 DNA-positive and -negative women participating in a nested case-control study of incident cervical neoplasia, Seventy-four women with cervical HPV-16 DNA and 656 cytologically normal HPV-16 DNA-negative subjects were interviewed and tested at two time points for viral DNA and once (at the later time) for VLP seroreactivity, Among subjects who were currently HPV-16 DNA-negative, seroreactivity odds ratios increased from 2.9 for 2-5 male sex partners (vs, 0 or 1) to 5.4 for 6-9 partners and 14.0 for greater than or equal to 10. Thus, prior cervical infection may be a major determinant of seroreactivity in HPV-16 DNA-negative women, This trend was not observed in HPV-16 DNA-positive subjects, Seroreactivity was independently associated with oral contraceptive use, particularly in HPV-16 DNA-negative subjects with use for greater than or equal to 10 years, Consequently, a possible role for virus-steroid hormone interactions in seroconversion is suggested. C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. DIGENE DIAGNOST & INFORMAT MANAGEMENT SERV,SILVER SPRING,MD. CETUS CORP,EMERYVILLE,CA 94608. KAISER PERMANENTE CTR HLTH RES,PORTLAND,OR. GEORGE WASHINGTON UNIV,WASHINGTON,DC. RI Hernandez, Jessica/G-6527-2011 NR 28 TC 60 Z9 62 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 NOV PY 1996 VL 174 IS 5 BP 937 EP 943 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VN181 UT WOS:A1996VN18100006 PM 8896493 ER PT J AU Andersson, S Makitalo, B Thorstensson, R Franchini, G Tartaglia, J Limbach, K Paoletti, E Putkonen, P Biberfeld, G AF Andersson, S Makitalo, B Thorstensson, R Franchini, G Tartaglia, J Limbach, K Paoletti, E Putkonen, P Biberfeld, G TI Immunogenicity and protective efficacy of a human immunodeficiency virus type 2 recombinant canarypox (ALVAC) vaccine candidate in cynomolgus monkeys SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PASSIVE-IMMUNIZATION; HIV-1 INFECTION; HTLV-IV; MACAQUES; GLYCOPROTEIN; CHIMPANZEES; PREVENTION; CHALLENGE; RESPONSES; INDUCTION AB The efficacy of a recombinant human immunodeficiency virus (HIV) type 2 canarypox (ALVAC HIV-2) vaccine candidate given alone or in combination with HIV-2 envelope gp125 or HIV-2 V3 synthetic peptides was investigated in 14 cynomolgus monkeys, High antibody titers to HIV-2 gp125 were demonstrated in monkeys given booster immunizations with gp125, Neutralizing antibody titers were low (less than or equal to 20) in all monkeys except 2. Significant lymphocyte proliferative responses to killed HIV-2 virions were observed in monkeys given booster immunizations with gp125, HIV-2-specific cytotoxic T lymphocytes were demonstrated prior to viral challenge in 3 of 12 monkeys, After challenge with homologous cell-free HIV-2 propagated in monkey cells, 4 of 10 monkeys immunized with ALVAC HIV-2 plus HIV-2 gp125 or V3 peptides were protected, as determined by negative virus isolation and polymerase chain reaction for viral DNA, Four monkeys immunized with ALVAC HIV-2 alone were not protected. All 12 control monkeys became infected, There was no correlation between the immunologic parameters studied and protection against infection in the vaccinated monkeys. C1 KAROLINSKA INST,CTR MICROBIOL & TUMOR BIOL,STOCKHOLM,SWEDEN. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. VIROGENET CORP,TROY,NY 12180. RP Andersson, S (reprint author), SWEDISH INST INFECT DIS CONTROL,S-10521 STOCKHOLM,SWEDEN. NR 41 TC 44 Z9 45 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 NOV PY 1996 VL 174 IS 5 BP 977 EP 985 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VN181 UT WOS:A1996VN18100011 PM 8896498 ER PT J AU Mdluli, K Sherman, DR Hickey, MJ Kreiswirth, BN Morris, S Stover, CK Barry, CE AF Mdluli, K Sherman, DR Hickey, MJ Kreiswirth, BN Morris, S Stover, CK Barry, CE TI Biochemical and genetic data suggest that InhA is not the primary target for activated isoniazid in Mycobacterium tuberculosis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID MOLECULAR MECHANISMS; CATALASE PEROXIDASE; RESISTANCE; DRUG; CHEMOTHERAPY; ETHIONAMIDE; ACIDS; KATG AB An examination of the pattern of lipid biosynthetic responses to isoniazid (INH) treatment of Mycobacterium tuberculosis and Mycobacterium smegmatis suggests that the mode of action of activated INH differs between these 2 organisms, Transformation of M. smegmatis with inhA on a plasmid construct conferred high-level resistance to INH, while the same construct failed to confer resistance upon M. tuberculosis, The inhA region from 2 clinical isolates whose resistance has been attributed to changes in the upstream promoter region has been cloned and was not sufficient to impart INH resistance to the level of the parent strain on sensitive M. tuberculosis, These putative mutant promoter elements appear to elevate expression levels of gene fusion reporter constructs, suggesting some noncausal connection between the observed mutations and the lipid metabolism of drug-resistant organisms, These results suggest that InhA is not the major target for activated INH in M. tuberculosis. C1 ROCKY MT LABS,NIAID,TB RES UNIT,HAMILTON,MT 59840. PATHOGENESIS CORP,LAB TB & MOL MICROBIOL,SEATTLE,WA. PUBL HLTH RES INST,TB CTR,NEW YORK,NY. US FDA,CTR BIOL EVALUAT & RES,LAB MYCOBACTERIA,BETHESDA,MD. RI Barry, III, Clifton/H-3839-2012; OI Stover, Charles/0000-0002-7406-1696 FU Intramural NIH HHS [Z01 AI000783-11] NR 25 TC 85 Z9 89 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 NOV PY 1996 VL 174 IS 5 BP 1085 EP 1090 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VN181 UT WOS:A1996VN18100026 PM 8896513 ER PT J AU Staat, MA KruszonMoran, D McQuillan, GM Kaslow, RA AF Staat, MA KruszonMoran, D McQuillan, GM Kaslow, RA TI A population-based serologic survey of Helicobacter pylori infection in children and adolescents in the United States SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CAMPYLOBACTER-PYLORI; EPIDEMIOLOGY; PREVALENCE AB To provide more accurate estimates of Helicobacter pylori infection in the US population, IgG antibody levels were measured in serum from 2581 persons aged 6-19 years examined during phase I of the third National Hearth and Nutrition Examination Survey. Overall, 24.8% of participants had evidence of H. pylori infection, Infection was strongly associated with increasing age (chi(2) trend, P < .01) and being nonwhite (17.0% of non-Hispanic whites vs. 40.1% of non-Hispanic blacks and 42.0% of Mexican Americans infected). In a multivariate logistic regression model, H. pylori infection was significantly associated with increasing age (odds ratio [OR] = 1.07/year), being nonwhite (non-Hispanic black OR = 2.6 or Mexican American OR = 1.8), poverty (OR = 1.5), crowding (OR = 5.6), and head of household education level (OR = 1.8). In Mexican Americans, infection was associated with birth outside the United States or Canada in the univariate analyses but was not significantly associated after adjustment for age, poverty, crowding, and head of household education level. C1 NIAID,NIH,BETHESDA,MD 20892. CTR DIS CONTROL & PREVENT,NATL CTR HLTH STAT,HYATTSVILLE,MD 20782. RP Staat, MA (reprint author), CHILDRENS HOSP & MED CTR,DIV INFECT DIS,3333 BURNET AVE,CINCINNATI,OH 45229, USA. NR 16 TC 112 Z9 116 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 NOV PY 1996 VL 174 IS 5 BP 1120 EP 1123 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VN181 UT WOS:A1996VN18100034 PM 8896521 ER PT J AU Fine, JD Moshell, A AF Fine, JD Moshell, A TI The national epidermolysis bullosa registry: A longitudinal epidemiologic project which can facilitate the performance of basic skin research. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV N CAROLINA,DEPT DERMATOL,CHAPEL HILL,NC 27514. UNIV N CAROLINA,DEPT EPIDEMIOL,CHAPEL HILL,NC 27514. NIAMSD,BETHESDA,MD. NATL EPIDERMOLYSIS BULLOSA REGISTRY,CHAPEL HILL,NC. NR 0 TC 0 Z9 0 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 NOV PY 1996 VL 107 IS 5 BP 15 EP 15 PG 1 WC Dermatology SC Dermatology GA VN440 UT WOS:A1996VN44000039 ER PT J AU Uitto, J Burgeson, RE Christiano, AM Moshell, AN AF Uitto, J Burgeson, RE Christiano, AM Moshell, AN TI Symposium on epidermolysis bullosa: Molecular genetics of the cutaneous basement membrane zone, Jefferson Medical College, Philadelphia, Pennsylvania, April 29 and 30, 1996 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT CUTANEOUS BIOL,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT BIOCHEM,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT MOL PHARMACOL,PHILADELPHIA,PA 19107. MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,BOSTON,MA 02114. HARVARD UNIV,COLL MED,DEPT DERMATOL,BOSTON,MA. COLUMBIA UNIV,DEPT DERMATOL,NEW YORK,NY 10027. NIAMSD,BETHESDA,MD 20892. RP Uitto, J (reprint author), THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT DERMATOL,PHILADELPHIA,PA 19107, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 1996 VL 107 IS 5 BP 787 EP 788 DI 10.1111/1523-1747.ep12371847 PG 2 WC Dermatology SC Dermatology GA VN440 UT WOS:A1996VN44000025 PM 8875967 ER PT J AU Yamamoto, T Polinsky, RJ Goldstein, DS Baucom, CE Kopin, IJ AF Yamamoto, T Polinsky, RJ Goldstein, DS Baucom, CE Kopin, IJ TI Plasma sulfoconjugated dopamine levels are normal in patients with autonomic failure SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID ORTHOSTATIC HYPOTENSION; CONJUGATED CATECHOLAMINES; SYSTEM; EXERCISE AB Plasma levels of norepinephrine (NE), dihydroxyphenylglycol (DHPG), dihydroxyphenylalanine (DOPA), dopamine (DA), and dihydroxyphenylacetic acid (DOPAC)-all of which are free catechols-and sulfoconjugated DA (DASO(4)) were determined in 14 normal subjects and 18 patients with neurogenic orthostatic hypotension caused by either multiple system atrophy (MSA) (n = 11) or pure autonomic failure (n = 7). Ail free catechols were normal in patients with MSA, whereas NE, DHPG, DA, and DOPAC levels were significantly lower in patients with pure autonomic failure. The levels of DA-SO,, however, did not statistically differ among the three groups. The different plasma levels of free catechols in MSA and pure autonomic failure are consistent with the view that peripheral sympathetic neurons are relatively preserved in MSA, whereas they are severely affected in pure autonomic failure. Because DASO, does not appear to be affected in pure autonomic failure, it appears likely that this metabolite is derived mainly from non-neural sources, such as the gastrointestinal tract, rather than from the sympathoadrenomedullary system. C1 NINCDS,CLIN NEUROSCI BRANCH,NATL INST HLTH,BETHESDA,MD 20892. SANDOZ PHARMACEUT CORP,HUMAN PHARMACOL DRUG SAFETY DEPT,E HANOVER,NJ. SANDOZ PHARMACEUT CORP,SANDOZ RES INST,E HANOVER,NJ. NR 19 TC 6 Z9 6 U1 0 U2 0 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 NOV PY 1996 VL 128 IS 5 BP 488 EP 491 DI 10.1016/S0022-2143(96)90045-1 PG 4 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA VR632 UT WOS:A1996VR63200007 PM 8900291 ER PT J AU McKeown, LP Williams, SB Hansmann, KE Krutzsch, H Gralnick, HR AF McKeown, LP Williams, SB Hansmann, KE Krutzsch, H Gralnick, HR TI Glycoprotein Ib alpha peptides inhibit thrombin and SFLLRN-induced platelet aggregation SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID BINDING; LOCALIZATION; DOMAINS AB The platelet glycoprotein Ib alpha (GPIb alpha) receptor contains a high-affinity binding site for thrombin that, when occupied, augments platelet activation and aggregation in part via the 7-transmembrane domain receptor (7-TMDR). We have constructed a series of peptides derived from GPIb alpha that encompass the amino acid sequence F216-T240. We have studied the effect(s) of these peptides on platelet aggregation induced by thrombin or by the 7-TMDR peptide SFLLRN. Twenty-four peptides were synthesized from the peptide sequence F216-T240. Several of the peptides derived from the sequence W219-V227 of GPIb alpha inhibited platelet aggregation, which was primarily dependent on the presence of the amino acid sequence A224-N226 (AEN). These data suggest that a region within the GPIb alpha chain modulates the platelet aggregation induced by alpha-thrombin. These GPIb alpha peptides did not interfere with platelet aggregation induced by other agonists-for example, collagen, ristocetin, calcium ionophore, or botrocetin-which indicates that these GPIb alpha peptide-platelet interaction(s) are specific. Our studies provide another potential mechanism for modulating platelet activation and aggregation via synthetic and natural peptides. C1 NIH,CTR CLIN,SERV HEMATOL,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NR 5 TC 3 Z9 3 U1 0 U2 0 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 NOV PY 1996 VL 128 IS 5 BP 492 EP 495 DI 10.1016/S0022-2143(96)90046-3 PG 4 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA VR632 UT WOS:A1996VR63200008 PM 8900292 ER EF