FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Garcia, LJ Pradhan, TK Weber, HC Moody, TW Jensen, RT AF Garcia, LJ Pradhan, TK Weber, HC Moody, TW Jensen, RT TI The gastrin-releasing peptide receptor is differentially coupled to adenylate cyclase and phospholipase C in different tissues SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE bombesin; neuromedin B; protein kinase C ID PROTEIN-KINASE-C; MOUSE PANCREATIC ACINI; BOMBESIN-LIKE PEPTIDES; CANCER CELL-LINES; SWISS 3T3 CELLS; CYCLIC-AMP; CAMP ACCUMULATION; EPITHELIAL-CELLS; AMYLASE RELEASE; GROWTH-FACTORS AB Recent studies suggest that in some tissues GRP receptor activation can both stimulate phospholipase C and the adenylate cyclase pathway and that activation of the latter pathway may be important in mediating some of its well-described growth effects. However, other studies suggest GRP-R may not be coupled to adenylate cyclase. To investigate this possibility, in the present study we determined the coupling of the GRP receptors to each pathway in mouse, rat, and guinea pig pancreatic acini and compared it to that in mouse Swiss 3T3 cells and human SCLC cells, all of which possess well-characterized GRP receptors. Moreover, we tested the effect of PKC activation on the ability of GRP-related peptides to increase cAMP accumulation in these tissues. Changes in cAMP levels were determined with or without IBMX present, with or without forskolin, or both to amplify small increases in cAMP. In mouse, rat and guinea pig pancreatic acini, murine Swiss 3T3 cells and human SCLC cells, GRP-related peptides caused a 600%, 500%, 250%, 300% and 60% increase, respectively, in [H-3]IP with 1-3 nM causing a half-maximal effect. In murine Swiss 3T3 cells, IBMX, forskolin, and IBMX plus forskolin caused a 300%, 3500% and 10500% increase in cAMP, respectively. GRP-related peptides and VIP caused an additional 70% increase in cAMP with GRP causing a half-maximal (EC50) increase in cAMP at 2.1 +/- 0.5 nM, which was not significantly different from the EC50 of 3.1 +/- 0.9 nM for increasing [H-3]IP in these cells. GRP-related peptides did not stimulate increases in cAMP in mouse, rat or guinea pig pancreatic acini or in SCLC cells either alone, with IBMX or forskolin or both. However, in pancreatic acini IBMX, forskolin or both increased cAMP 3 to 8-, IO to 500-, and 100 to 1000-fold increase and the addition of VIP caused an additional 20-, 2- and 3-fold increase in cAMP in the different species. In mouse pancreatic acini with TPA alone or IBMX plus TPA, neither bombesin nor GRP increased cAMP. Furthermore, in mouse pancreatic acini, neither TPA nor TPA plus IBMX altered basal or VIP-stimulated increases in cAMP. In mouse Swiss 3T3 cells TPA significantly increased cAMP stimulated by Bn, GRP or VIP. These results demonstrated that GRP receptor activation in normal tissues from three different species and a human tumoral cell line do not result in adenylate cyclase activation, whereas in Swiss 3T3 cells it causes such activation. The results suggest that the difference in coupling to adenylate cyclase is likely at least partially due to a difference in coupling to an adenylate cyclase subtype whose activation is regulated by PKC. Therefore, the possible growth effects mediated by this receptor in different embryonic or tumoral cells through activation of adenylate cyclase are not likely to he an important intracellular pathway for these effects in normal tissues. (C) 1997 Elsevier Science B.V. C1 NIDDK,DIGEST DIS BRANCH,NIH,BETHESDA,MD 20892. UNIV EXTREMADURA,DEPT PHYSIOL,CACERES 10080,SPAIN. NCI,BIOMARKERS & PREVENT RES BRANCH,NIH,BETHESDA,MD 20892. RI Garcia-Marin, Luis /L-4680-2014 OI Garcia-Marin, Luis /0000-0002-1795-7381 NR 46 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD MAY 27 PY 1997 VL 1356 IS 3 BP 343 EP 354 DI 10.1016/S0167-4889(97)00007-4 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XD806 UT WOS:A1997XD80600011 PM 9194577 ER PT J AU Smith, MA Zhang, LX Lyons, WE Mamounas, LA AF Smith, MA Zhang, LX Lyons, WE Mamounas, LA TI Anterograde transport of endogenous brain-derived neurotrophic factor in hippocampal mossy fibers SO NEUROREPORT LA English DT Article DE anterograde transport; brain-derived neurotrophic factor; dentate gyrus; hippocampus; immunocytochemistry; in situ hybridization; neuronal plasticity; neurotrophin; seizures ID MESSENGER-RNA LEVELS; RAT-BRAIN; NEURONAL PLASTICITY; KAINIC ACID; BDNF; EXPRESSION; RECEPTORS; SEIZURE; STRESS; INCREASES AB NEUROTROPHIC factors such as brain-derived neurotrophic factor (BDNF) are assumed to provide trophic support via a target-derived, retrograde mechanism of action. However, recent studies suggest that neurotrophic factors can act in an autocrine fashion and perhaps even in an anterograde direction similar to neurotransmitters. To further explore this hypothesis, we compared the neuroanatomical pattern of BDNF mRNA and protein in response to electroconvulsive seizures (ECS) or kainic acid-induced seizure activity. Using in situ hybridization, we found that chronic ECS induced BDNF mRNA predominantly in the granule neurons of the dentate gyrus. However, immunohistochemistry with an anti-BDNF antibody revealed that ECS increased endogenous BDNF protein in the messy fibers, which are composed of axons projecting from the granule neurons of the dentate gyrus to the CA3 pyramidal layer of the hippocampus. Kainic acid administration (10 mg/kg, i.p., once) was used to lesion CA3 neurons selectively, as these are a possible retrograde source of BDNF protein in messy fibers. Three weeks later, a prolonged elevation of BDNF mRNA in granule neurons, but not elsewhere in hippocampus, was accompanied by an increase in BDNF protein in the messy fibers. These results suggest that BDNF was transcribed and translated in granule neuron cell bodies but transported in an anterograde direction to provide trophic support of CA3 pyramidal neurons. C1 NIA,GERONTOL RES CTR,MOL NEUROBIOL UNIT,LAB BIOL CHEM,UNIT 12,NIH,BALTIMORE,MD 21224. NIMH,BIOL PSYCHIAT BRANCH,NIH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD. NR 25 TC 98 Z9 100 U1 1 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 MAY 27 PY 1997 VL 8 IS 8 BP 1829 EP 1834 DI 10.1097/00001756-199705260-00008 PG 6 WC Neurosciences SC Neurosciences & Neurology GA XG766 UT WOS:A1997XG76600008 PM 9223060 ER PT J AU Alexander, GE Saunders, AM Szczepanik, J Strassburger, TL Pietrini, P Dani, A Furey, ML Mentis, MJ Roses, AD Rapoport, SI Schapiro, MB AF Alexander, GE Saunders, AM Szczepanik, J Strassburger, TL Pietrini, P Dani, A Furey, ML Mentis, MJ Roses, AD Rapoport, SI Schapiro, MB TI Relation of age and apolipoprotein E to cognitive function in Down syndrome adults SO NEUROREPORT LA English DT Article DE aging; Alzheimer's disease; apolipoprotein E; cognition; Down syndrome; neuropsychology ID ALZHEIMERS-DISEASE; DEMENTIA; EDUCATION; IMPAIRMENT; PREVALENCE AB To test the cognitive effects of aging and apolipoprotein E (APOE) in individuals at high risk for Alzheimer's disease (AD), we assessed APOE genotypes and performance on a battery of neuropsychological tests in 41 nondemented, Down syndrome (DS) adults. Old DS subjects (ages 41-61 years) showed poorer memory and orientation scores than young DS adults (ages 22-38 years), but the groups did not differ in other measures after we controlled for intellectual function. Language ability was inversely related to APOE genotype, even after age was controlled for, with the presence of the epsilon 2 allele corresponding to better language skills than epsilon 4. Age-related cognitive changes in non-demented DS adults are consistent with the early effects of AD. The relationship between basic linguistic skills and APOE genotype supports this genetic factor in influencing the development of dementia and AD neuropathology in DS. C1 DUKE UNIV,MED CTR,DIV NEUROL,JOSEPH & KATHLEEN BRYAN ALZHEIMERS DIS RES CTR,DURHAM,NC 27710. RP Alexander, GE (reprint author), NIA,NEUROSCI LAB,NIH,BLDG 10,RM 6C414,BETHESDA,MD 20892, USA. RI Furey, Maura/H-5273-2013 FU NIA NIH HHS [5R35 AG-07922, 5P50 AG-05128] NR 25 TC 30 Z9 31 U1 1 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 MAY 27 PY 1997 VL 8 IS 8 BP 1835 EP 1840 DI 10.1097/00001756-199705260-00009 PG 6 WC Neurosciences SC Neurosciences & Neurology GA XG766 UT WOS:A1997XG76600009 PM 9223061 ER PT J AU Humphrey, JS Salim, A Erdos, MR Collins, FS Brody, LC Klausner, RD AF Humphrey, JS Salim, A Erdos, MR Collins, FS Brody, LC Klausner, RD TI Human BRCA1 inhibits growth in yeast: Potential use in diagnostic testing SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID OVARIAN-CANCER; MUTATIONS; BREAST; PROTEIN; GENE; FAMILIES; P53 AB Germline-inactivating mutations of BRCA1 result in a hereditary predisposition to breast and ovarian cancer, Truncating mutations of BRCA1 predispose to cancer and can be ascertained by protein truncation testing or sequencing, However, cancer-predisposing missense mutations of BRCA1 are difficult to distinguish from polymorphisms by genetic testing methods currently used, Here we show that expression of BRCA1 or BRCA1 fused to a GAL4 activation domain in Saccharomyces cerevesiae inhibits growth, resulting in small colonies easily distinguishable from vector-transformed controls, The growth inhibitory effect can be localized to sequences encoding the recently described BRCA1 C-terminal domains, Growth suppression by a BRCA1 fusion protein is not influenced by introduction of neutral polymorphisms but is diminished or abolished by frameshift, nonsense, or disease-associated missense mutations located in the C-terminal 305 amino acids of BRCA1, These observations may permit the functional significance of many BRCA1 sequence changes to be assessed in yeast, Additionally, the correlation of growth suppression with wild-type forms of BRCA1 suggests that the assay may be capable of detecting functionally conserved interactions between the evolutionarily conserved BRCA1 C-terminal domains and cellular elements found in both human and yeast cells. C1 UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. HOWARD HUGHES MED INST,RES SCHOLARS PROGRAM,BETHESDA,MD 20892. NIH,NATL HUMAN GENOME RES INST,GENE TRANSFER LAB,BETHESDA,MD 20892. NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892. RP Humphrey, JS (reprint author), NCI,NIH,MED BRANCH,18 LIB DR,MSC 5430,BLDG 18T,ROOM 101,BETHESDA,MD 20892, USA. NR 31 TC 90 Z9 92 U1 4 U2 26 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 MAY 27 PY 1997 VL 94 IS 11 BP 5820 EP 5825 DI 10.1073/pnas.94.11.5820 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XB711 UT WOS:A1997XB71100063 PM 9159158 ER PT J AU Mushegian, AR Bassett, DE Boguski, MS Bork, P Koonin, EV AF Mushegian, AR Bassett, DE Boguski, MS Bork, P Koonin, EV TI Positionally cloned human disease genes: Patterns of evolutionary conservation and functional motifs SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DNA-POLYMERASE-I; ESCHERICHIA-COLI; 3'-5' EXONUCLEASE; PROTEIN; PHOSPHORYLATION; FRAGMENT; CLONING AB Positional cloning has already produced the sequences of more than 70 human genes associated with specific diseases, In addition to their medical importance, these genes are of interest as a set of human genes isolated solely on the basis of the phenotypic effect of the respective mutations, We analyzed the protein sequences encoded by the positionally cloned disease genes using an iterative strategy combining several sensitive computer methods, Comparisons to complete sequence databases and to separate databases of nematode, yeast, and bacterial proteins showed that for most of the disease gene products, statistically significant sequence similarities are detectable in each of the model organisms, Only the nematode genome encodes apparent orthologs with conserved domain architecture for the majority of the disease genes, In yeast and bacterial homologs, domain organization is typically not conserved, and sequence similarity is limited to individual domains, Generally, human genes complement mutations only in orthologous yeast genes, Most of the positionally cloned genes encode large proteins with several globular and nonglobular domains, the functions of some or all of which are not known. We detected conserved domains and motifs not described previously in a number of proteins encoded by disease genes and predicted functions for some of them, These predictions include an ATP-binding domain in the product of hereditary nonpolyposis colon cancer gene (a MutL homolog), which is conserved in the HS90 family of chaperone proteins, type II DNA topoisomerases, and histidine kinases, and a nuclease domain homologous to bacterial RNase D and the 3'-5' exonuclease domain of DNA polymerase I in the Werner syndrome gene product. C1 NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NIH,BETHESDA,MD 20894. JOHNS HOPKINS UNIV,SCH MED,DEPT MOL BIOL & GENET,BALTIMORE,MD 21205. EUROPEAN MOL BIOL LAB,D-69012 HEIDELBERG,GERMANY. MAX DELBRUCK CTR,D-13125 BERLIN,GERMANY. RI Bork, Peer/F-1813-2013; OI Bork, Peer/0000-0002-2627-833X; Mushegian, Arcady/0000-0002-6809-9225 NR 48 TC 198 Z9 199 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 27 PY 1997 VL 94 IS 11 BP 5831 EP 5836 DI 10.1073/pnas.94.11.5831 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XB711 UT WOS:A1997XB71100065 PM 9159160 ER PT J AU Smith, MR Duhe, RJ Liu, YL Farrar, WL AF Smith, MR Duhe, RJ Liu, YL Farrar, WL TI Microinjected cDNA encoding JAK2 protein-tyrosine kinase induces DNA synthesis in NIH 3T3 cells SO FEBS LETTERS LA English DT Article DE proto-oncogene; microinjection; protein-tyrosine kinase; Janus kinase; tyrphostin AG-490 ID RECEPTOR; ACTIVATION; DROSOPHILA; PHOSPHORYLATION; ERYTHROPOIETIN; INHIBITION; PROLACTIN; HOPSCOTCH; ONCOGENE AB Microinjection of expression plasmids encoding either JAK2 or hyperactive (N Delta 661)rJAK2 into serum-starved NIH 3T3 cells resulted in 20-30-fold induction of DNA synthesis, Control microinjections of buffer or parental pcDNA3 vector resulted in only 3-5-fold induction of DNA synthesis. Induction of DNA synthesis was blocked when plasmid encoding JAK2 was microinjected in the presence of the JAK2-selective inhibitor AG-490, whereas AG-490 did not block DNA synthesis induced by microinjected plasmid encoding (N Delta 661)rJAK2. The ability of JAK2 to initiate the G(o)/S cell cycle transition is comparable to that of other proto-oncogenes, and supports a mechanistic role for overexpressed Janus kinases in carcinogenesis. (C) 1997 Federation of European Biochemical Societies. C1 NCI,INTRAMURAL RES SUPPORT PROGRAM,SCI APPLICAT INT CORP,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NCI,CYTOKINE MOL MECHANISMS SECT,LAB MOL IMMUNOREGULAT,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NR 24 TC 9 Z9 9 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 MAY 26 PY 1997 VL 408 IS 3 BP 327 EP 330 DI 10.1016/S0014-5793(97)00456-0 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA XD634 UT WOS:A1997XD63400017 PM 9188787 ER PT J AU Rauschecker, JP Tian, B Pons, T Mishkin, M AF Rauschecker, JP Tian, B Pons, T Mishkin, M TI Serial and parallel processing in rhesus monkey auditory cortex SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE macaque monkey; Macaca mulatta; supratemporal plane; AI lesion; medial geniculate nucleus; fluorescent tracers ID CORTICO-CORTICAL CONNECTIONS; CAT CEREBRAL-CORTEX; OWL MONKEY; TONOTOPIC ORGANIZATION; SOMATOSENSORY CORTEX; INFERIOR COLLICULUS; SUPERIOR COLLICULUS; AOTUS-TRIVIRGATUS; EARLY BLINDNESS; MACAQUE MONKEY AB Auditory cortex on the exposed supratemporal plane in four anesthetized rhesus monkeys was mapped electrophysiologically with both pure-tone (PT) and broad-band complex sounds. The mapping confirmed the existence of at least three tonotopic areas. Primary auditory cortex, AT, was then aspirated, and the remainder of the cortex on the supratemporal plane was remapped. PT-responses in the caudomedial area, CM, were abolished in all animals but one, in which they were restricted to the high-frequency range. Some CM sites were still responsive to complex stimuli. In contrast to the effects on CM, no significant changes were detectable in the rostral area, R. After mapping cortex in four additional monkeys, injections were made with different tracers into matched best-frequency regions of AI, R, and CM. Injections in Al and R led to retrograde labeling of neurons in all three subdivisions of the medial geniculate (MG) nucleus (MGv, MGd, and MGm), as well as nuclei outside MG, whereas CM injections led to only sparse labeling of neurons in a restricted zone of the lateral MGd and, possibly, MGm, in addition to labeling in non-MG sites. The combined results suggest that MGv sends direct projections in parallel to areas Al and R, which drive PT-responses in both areas. PT-responses in area CM, however, appear to be driven by input relayed serially from AI. The direct input to CM from MGd and other thalamic nuclei may thus be capable of mediating responses only to broad-band sounds. (C) 1997 Wiley-Liss, Inc. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT NEUROSURG,WINSTON SALEM,NC 27157. NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. RP Rauschecker, JP (reprint author), GEORGETOWN INST COGNIT & COMPUTAT SCI,3970 RESERVOIR RD NW,RES BLDG,RM WP15,WASHINGTON,DC 20007, USA. RI Rauschecker, Josef/A-4120-2013 NR 43 TC 235 Z9 242 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD MAY 26 PY 1997 VL 382 IS 1 BP 89 EP 103 PG 15 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA WW932 UT WOS:A1997WW93200006 PM 9136813 ER PT J AU Qasba, PK Balaji, PV Rao, VSR AF Qasba, PK Balaji, PV Rao, VSR TI Conformational analysis of Asn-linked oligosaccharides: Implications in biological processes SO JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM LA English DT Article; Proceedings Paper CT Symposium of the American-Chemical-Society on Carbohydrate Modeling CY MAR, 1995 CL ANAHEIM, CA SP Amer Chem Soc DE conformation; glycolipid; glycoprotein; molecular dynamics; oligosaccharides; N-linked oligosaccharide processing ID MOLECULAR-DYNAMICS SIMULATIONS; ALPHA-D-MANNOSIDASE; COMPLEX-TYPE OLIGOSACCHARIDES; N-ACETYLGLUCOSAMINIDASE-H; RAT-LIVER; CRYSTAL-STRUCTURE; BIANTENNARY OCTASACCHARIDE; 3-DIMENSIONAL STRUCTURES; GLYCOSYLATION SITES; CONCANAVALIN-A AB Molecular dynamics simulations of several Asn-linked oligosaccharides carried out recently have been summarized. These oligosaccharides are flexible and the core alpha 1 --> 3- and alpha 1 --> 6-linkages play important roles in determining the overall shape of the molecule. The orientation of the 1 --> 6-arm is affected not only by changes in chi but also by changes in phi and psi around the alpha 1 --> 6-linkage. The processing of Man(9)GlcNAc(2) to Man(5)GlcNAc(2) during the biosynthesis of Asn-linked oligosaccharides proceeds in well-defined 'conformation driven' pathways. These molecular dynamics studies rationalize spectroscopic and biochemical observations such as the rate of cleavage of alpha 1 --> 2-linked mannoses by alpha-mannosidases, the action of beta-1 --> 4-galactosyltransferase on biantennary oligosaccharides, and the binding affinities of oligosaccharide ligands to the asialoglycoprotein receptor. (C) 1997 Elsevier Science B.V. RP Qasba, PK (reprint author), NCI, STRUCT GLYCOL SECT,LAB EXPT & COMPUTAT BIOL,NIH, BLD 469,ROOM 221, POB B, FREDERICK, MD 21702 USA. OI Balaji, Petety/0000-0002-6018-6957 NR 75 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-1280 J9 J MOL STRUC-THEOCHEM JI Theochem-J. Mol. Struct. PD MAY 26 PY 1997 VL 395 BP 333 EP 360 DI 10.1016/S0166-1280(96)04543-5 PG 28 WC Chemistry, Physical SC Chemistry GA XK396 UT WOS:A1997XK39600024 ER PT J AU Girard, M vanderRyst, E BarreSinoussi, F Nara, P Tartaglia, J Paoletti, E Blondeau, C Jennings, M Verrier, F Meignier, B Fultz, PN AF Girard, M vanderRyst, E BarreSinoussi, F Nara, P Tartaglia, J Paoletti, E Blondeau, C Jennings, M Verrier, F Meignier, B Fultz, PN TI Challenge of chimpanzees immunized with a recombinant canarypox-HIV-1 virus SO VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NEUTRALIZING ANTIBODY; VACCINE PROTECTION; CYNOMOLGUS MONKEYS; INFECTION; TYPE-1; HIV; GP120; CELLS; GLYCOPROTEIN AB To evaluate the potential protective efficacy of a live recombinant human immunodeficiency virus type 1 (HIV-1) canarypox vaccine candidate, two chimpanzees were immunized five times with ALVAC-HIV-1 vCP250, a recombinant canarypox virus that expresses the HIV-I-IIIB(LAI) gp120/TM, gag, and protease gene products. One month after the last booster inoculation, the animals were challenged by intravenous injection of cell-associated virus in the form of peripheral blood mononuclear cells from an HIV-1(IIIB(LAI))-infected chimpanzee. One chimpanzee with a neutralizing antibody titer to HIV-1(IIIB(LAI)) of 128 at the time of challenge was protected, whereas both the second animal, with a neutralizing antibody titer of 32, and a naive control animal became infected. At 5 months after challenge, the protected chimpanzee and a third animal, previously immunized with various HIV-1(MN) antigens, were given a booster inoculation. The two animals were challenged intravenously 5 weeks later with twenty 50% tissue culture infectious doses of cell-free HIV-1(DH12), a heterologous subtype a isolate. Neither chimpanzee had neutralizing antibodies to HIV-1(DH12), and neither one was protected from infection with this isolate. The immune responses elicited by vaccination against HIV-1(IIIB(LAI)) or HIV-1(MN) did not, therefore, protect the animals from challenge with the heterologous cell-free HIV-1(DH12). (C) 1997 Academic Press. C1 INST PASTEUR,F-75015 PARIS,FRANCE. NCI,FREDERICK,MD 20892. VIROGENET CORP,TROY,NY 12180. PARTEUR MERIEUX CONNAUGHT,MARCY LETOILE,FRANCE. NYU,MED CTR,LAB EXPT SURG PRIMATES,NEW YORK,NY 10016. UNIV ALABAMA,SCH MED,BIRMINGHAM,AL 35487. UFS,DEPT VIROL,BLOEMFONTEIN,SOUTH AFRICA. RI Barre-Sinoussi, Francoise/G-8355-2011 NR 39 TC 29 Z9 31 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD MAY 26 PY 1997 VL 232 IS 1 BP 98 EP 104 DI 10.1006/viro.1997.8560 PG 7 WC Virology SC Virology GA XA882 UT WOS:A1997XA88200011 PM 9185593 ER PT J AU Xu, H Rizzo, LV Silver, PB Caspi, RR AF Xu, H Rizzo, LV Silver, PB Caspi, RR TI Uveitogenicity is associated with a Th1-like lymphokine profile: Cytokine-dependent modulation of early and committed effector T cells in experimental autoimmune uveitis SO CELLULAR IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; TUMOR-NECROSIS-FACTOR; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; UVEORETINITIS EAU; ADOPTIVE TRANSFER; HELPER CELLS; S-ANTIGEN; IFN-GAMMA; MICE; DISEASE AB This study addresses the nature of the pathogenic effector T cell in experimental autoimmune uveoretinitis and the effect of different cytokines on these cells in vitro. Lymph node cells of B10.RIII mice immunized with the uveitogenic peptide 161-180 of interphotoreceptor retinoid binding protein were cultured with the peptide with or without IL-12, IL-4, or anti-IL-4. An antigen-specific T cell line was subsequently derived from these cells. Primary cultures of immune lymph node cells stimulated with the peptide proliferated and produced IL-2 and some IL-4, but no IFN-gamma. The addition of recombinant IL-12 resulted in abundant production of IFN-gamma, which was blocked by the addition of IL-4 and was enhanced by anti-IL-4. Only those cultures that produced IFN-gamma in vitro were uveitogenic in vivo. A long-term uveitogenic T cell line, initially derived in the presence of IL-12, produced IFN-gamma and IL-2, but not IL-4, and was CD4(+) (Th1-like). Antigen-specific proliferation and IFN-gamma production of the line were enhanced by exogenous IL-4, TGF-beta, IL-2, IL-6, IL-7, and IL-9 and were inhibited by IL-10 and TNF-alpha. Our results provide support for the hypothesis that the uveitogenic effector T cell has a Th1-like phenotype. Furthermore, the data suggest that the effects of the cytokine milieu on fully differentiated Th1 effecters may differ considerably from their effects on less mature stages of antigen-specific T cells. RP Xu, H (reprint author), NEI, NIH, IMMUNOL LAB, BETHESDA, MD 20892 USA. RI Rizzo, Luiz Vicente/B-4458-2009 NR 42 TC 75 Z9 78 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD MAY 25 PY 1997 VL 178 IS 1 BP 69 EP 78 DI 10.1006/cimm.1997.1121 PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA XE124 UT WOS:A1997XE12400009 PM 9184700 ER PT J AU Courtois, SJ Woodworth, CD Degreef, H Garmyn, M AF Courtois, SJ Woodworth, CD Degreef, H Garmyn, M TI Early ultraviolet B-induced G1 arrest and suppression of the malignant phenotype by wild-type p53 in human squamous cell carcinoma cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID HUMAN KERATINOCYTES; FUNCTION MUTATIONS; TUMOR SUPPRESSION; UV-IRRADIATION; CANCER-CELLS; DNA-DAMAGE; GENE; EXPRESSION; PROTEIN; GROWTH AB Wild-type p53 (wt-p53) negatively controls cell cycle progression after cellular stress mediating either a temporary growth arrest or apoptosis, depending on the cell type and nature of the cellular stress. The aberrant proliferation which is characteristic of tumor cells may be suppressed by exogenous wt-p53 and appears to depend strongly on the level of reexpression. We performed retroviral-mediated gene transfer of wt-p53 into a human squamous cell carcinoma cell line from the head and neck region (A253 cell line) lacking endogenous p53. This allowed us to study the effect of wt-p53 on the malignant phenotype and on the response to the DNA damaging agent ultraviolet B (UVB). Restoration of wt-p53 in malignant keratinocytes suppressed tumorigenicity in nude mice although p53-reconstituted cells eventually formed small tumors with long latency. Cells derived from these tumors showed reduced expression of wt-p53. Exogenous wt-p53 increased baseline mRNA expression of the small proline rich proteins 1 and 2, consistent with a prodifferentiating effect. After exposure to a biological WE dose, only p53-positive A253 cells underwent an early and transient G1 arrest. Both p53-positive and -negative A253 cells displayed a late G2 delay/arrest. We conclude that reexpression of wt-p53 in squamous cell carcinoma A253 cells decreases their malignant phenotype and reestablishes a G1 checkpoint after UVB. (C) 1997 Academic Press. C1 UNIV HOSP ST RAPHAEL,DEPT DERMATOL,B-3000 LOUVAIN,BELGIUM. NCI,BETHESDA,MD 20892. NR 51 TC 24 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 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAY 25 PY 1997 VL 233 IS 1 BP 135 EP 144 DI 10.1006/excr.1997.3537 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA XC182 UT WOS:A1997XC18200015 PM 9184083 ER PT J AU Rapaport, MH McAllister, CG Pickar, D Tamarkin, L Kirch, DG Paul, SM AF Rapaport, MH McAllister, CG Pickar, D Tamarkin, L Kirch, DG Paul, SM TI CSF IL-1 and IL-2 in medicated schizophrenic patients and normal volunteers SO SCHIZOPHRENIA RESEARCH LA English DT Article DE biological psychiatry; CSF; IL-1; IL-2; immunology; schizophrenia ID SOLUBLE INTERLEUKIN-2 RECEPTORS; MONOZYGOTIC TWINS DISCORDANT; CEREBROSPINAL-FLUID; RELEASE; BRAIN; SERUM; MONOAMINE; VOLUME; SYSTEM; CELLS AB It is clear that cytokines exert a variety of modulatory actions on the central nervous system. As part of our work exploring the relationship between immune activation and psychosis, we measured cerebrospinal fluid (CSF) IL-1 alpha and IL-2 levels in 60 medicated schizophrenic patients and in 21 normal volunteers using a competitive enzyme immunoassay. The two groups did not differ significantly in their mean cytokine levels: 1.01 (0.149) ng/ml (patients) vs. 1.28 (0.150) ng/ml (controls) for IL-1 alpha and 0.970 (0.038) ng/ml (patients) vs. 1.25 (0.086) ng/ml (controls) for IL-2. There was a significant positive correlation between CSF IL-1 alpha and IL-2 levels for all subjects (r=0.50, n=44, p=0.0001). C1 VET AFFAIRS MED CTR,PSYCHIAT SERV,SAN DIEGO,CA 92161. UNIV PITTSBURGH,DEPT PSYCHIAT,PITTSBURGH,PA. NIMH,EXPT THERAPEUT BRANCH,BETHESDA,MD 20892. MED COLL GEORGIA,AUGUSTA,GA 30912. RP Rapaport, MH (reprint author), UNIV CALIF SAN DIEGO,SCH MED,DEPT PSYCHIAT 0985,PSYCHOPHARMACOL RES PROGRAM,LA JOLLA,CA 92037, USA. NR 33 TC 36 Z9 37 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY 24 PY 1997 VL 25 IS 2 BP 123 EP 129 DI 10.1016/S0920-9964(97)00008-X PG 7 WC Psychiatry SC Psychiatry GA XE386 UT WOS:A1997XE38600005 PM 9187011 ER PT J AU Pomes, A Kempner, E Rohrer, S AF Pomes, A Kempner, E Rohrer, S TI Target size analysis of an avermectin binding site from Drosophila melanogaster SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY LA English DT Article DE ivermectin binding site; Drosophila melanogaster; target size; radiation inactivation ID POTENT ANTHELMINTIC AGENTS; CAENORHABDITIS-ELEGANS RNA; RADIATION INACTIVATION; XENOPUS-OOCYTES; CHLORIDE CURRENT; ACETYLCHOLINESTERASE; EXPRESSION; IDENTIFICATION; FAMILY AB A high-affinity avermectin binding site from Drosophila melanogaster head membranes was subjected to target size analysis by radiation inactivation in order to determine the functional unit size. Using the [H-3]ivermectin binding assay to assess ligand binding activity, the target size was determined to be 44.3+/-3.9 kDa, This result suggests that the size of the functional unit required for high-affinity ligand binding is a monomer. The membrane-associated acetylcholinesterase present in the Drosophila head membranes was also analyzed by radiation inactivation and served as a control. By monitoring enzymatic activity, the functional unit size of the Drosophila acetylcholinesterase was determined to be 70+/-9.7 kDa. This corresponds to the molecular weight of a dimer composed of a 55 kDa subunit and a 16-18 kDa subunit. C1 MERCK & CO INC,MERCK SHARP & DOHME RES LABS,DEPT CELL & BIOCHEM PHYSIOL,RAHWAY,NJ 07065. NIAMSD,NIH,BETHESDA,MD 20892. NR 26 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4838 J9 BBA-PROTEIN STRUCT M JI Biochim. Biophys. Acta-Protein Struct. Molec. Enzym. PD MAY 23 PY 1997 VL 1339 IS 2 BP 233 EP 238 DI 10.1016/S0167-4838(97)00006-X PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XB635 UT WOS:A1997XB63500007 PM 9187243 ER PT J AU Johren, O Imboden, H Hauser, W Maye, I Sanvitto, GL Saavedra, JM AF Johren, O Imboden, H Hauser, W Maye, I Sanvitto, GL Saavedra, JM TI Localization of angiotensin-converting enzyme, angiotensin II, angiotensin II receptor subtypes, and vasopressin in the mouse hypothalamus SO BRAIN RESEARCH LA English DT Article DE brain angiotensin system; [I-125]Sar(1)-Ang II binding; [I-125]CGP42112 binding; AT(1) receptor; AT(2) receptor; immunocytochemistry ID CENTRAL-NERVOUS-SYSTEM; RAT-BRAIN; BLOOD-PRESSURE; INVITRO AUTORADIOGRAPHY; BINDING-SITES; PITUITARY ANGIOTENSIN; BASAL FOREBRAIN; TYPE-2 RECEPTOR; DEFICIENT MICE; RABBIT BRAIN AB The hypothalamic angiotensin II (Ang II) system plays an important role in pituitary hormone release. Little is known about this system in the mouse brain. We studied the distribution of angiotensin-converting-enzyme (ACE), Ang II, Ang II receptor subtypes, and vasopressin in the hypothalamus of adult male mice. Autoradiography of binding of the ACE inhibitor [I-125]351A revealed law levels of ACE throughout the hypothalamus. Ang II- and vasopressin-immunoreactive neurons and fibers were detected in the paraventricular, accessory magnocellulary, and supraoptic nuclei, in the retrochiasmatic part of the supraoptic nucleus and in the median eminence. Autoradiography of Ang II receptors was performed using [I-125]Sar(1)-Ang II binding. Ang II receptors were present in the paraventricular, suprachiasmatic, arcuate and dorsomedial nuclei, and in the median eminence. In all areas [I-125]Sar(1)-Ang II binding was displaced by the AT(1) receptor antagonist losartan, indicating the presence of AT(1) receptors. In the paraventricular nucleus [I-125]Sar(1)-Ang II binding was displaced by Ang II (K-i = 7.6 x 10(-9)) and losartan (K-i 1.4 x 10(-7)) but also by the AT(2) receptor ligand PD 123319 (K-i = 5.0 x 10(-7)). In addition, a low amount of AT(2) receptor binding was detected in the paraventricular nucleus using [I-125]CGP42112 as radioligand, and the binding was displaced by Ang II (K-i = 2.4 x 10(-9)), CGP42112 (K-i = 7.9 x 10(-10)), and PD123319 (K-i = 2.2 x 10(-7)). ACE, Ang II, and AT(1) as well as AT(2) receptor subtypes are present in the mouse hypothalamus. Our data are the basis for further studies on the mouse brain Ang II system. C1 UNIV BERN,DIV NEUROBIOL,CH-3012 BERN,SWITZERLAND. RP Johren, O (reprint author), NIMH,PHARMACOL SECT,CLIN SCI LAB,10 CTR DR,MSC 1514,BLDG 10,ROOM 2D-57,BETHESDA,MD 20892, USA. RI Johren, Olaf/G-6967-2011 NR 43 TC 68 Z9 68 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 23 PY 1997 VL 757 IS 2 BP 218 EP 227 DI 10.1016/S0006-8993(97)00220-5 PG 10 WC Neurosciences SC Neurosciences & Neurology GA XC509 UT WOS:A1997XC50900006 PM 9200750 ER PT J AU Kliger, Y Aharoni, A Rapaport, D Jones, P Blumenthal, R Shai, Y AF Kliger, Y Aharoni, A Rapaport, D Jones, P Blumenthal, R Shai, Y TI Fusion peptides derived from the HIV type 1 glycoprotein 41 associate within phospholipid membranes and inhibit cell-cell fusion - Structure-function study SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; FLUORESCENTLY-LABELED ANALOGS; INFLUENZA HEMAGGLUTININ; OLIGOMERIC STRUCTURE; VIRAL FUSION; N-TERMINUS; TRANSMEMBRANE GLYCOPROTEIN; ENVELOPE GLYCOPROTEIN; SYNCYTIUM FORMATION; CHANNEL FORMATION AB The fusion domain of human immunodeficiency virus (HIV-1) envelope glycoprotein (gp120-gp41) is a conserved hydrophobic region located at the N terminus of the transmembrane glycoprotein (gp41). A V2E mutant has been shown to dominantly interfere with wild type envelope-mediated syncytium formation and virus infectivity. To understand this phenomenon, a 33-residue peptide (wild type, WT) identical to the N-terminal segment of gp41 and its V2E mutant were synthesized, fluorescently labeled, and characterized, Both peptides inhibited HIV-1 envelope-mediated cell cell fusion and had similar alpha-helical content in membrane mimetic environments, Studies with fluorescently labeled peptide analogues revealed that both peptides have high affinity for phospholipid membranes, are susceptible to digestion by proteinase-K in their membrane-bound state, and tend to self- and coassemble in the membranes. In SDS-polyacrylamide gel electrophoresis the WT peptide formed dimers as well as higher order oligomers, whereas the V2E mutant only formed dimers. The WT, but not the V2E mutant, induced liposome aggregation, destabilization, and fusion. Moreover, the V2E mutant inhibited vesicle fusion induced by the WT peptide, probably by forming inactive heteroaggregates. These data form the basis for an explanation of the mechanism by which the gp41 V2E mutant inhibits HIV-1 infectivity in cells when co expressed with WT gp41. C1 WEIZMANN INST SCI,DEPT MEMBRANE RES & BIOPHYS,IL-76100 REHOVOT,ISRAEL. NCI,SECT MEMBRANE STRUCT & FUNCT,NIH,BETHESDA,MD 20892. NR 68 TC 140 Z9 144 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 23 PY 1997 VL 272 IS 21 BP 13496 EP 13505 DI 10.1074/jbc.272.21.13496 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XA062 UT WOS:A1997XA06200009 PM 9153194 ER PT J AU deCaestecker, MP Hemmati, P LarischBloch, S Ajmera, R Roberts, AB Lechleider, RJ AF deCaestecker, MP Hemmati, P LarischBloch, S Ajmera, R Roberts, AB Lechleider, RJ TI Characterization of functional domains within Smad4/DPC4 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR-BETA; TGF-BETA; RECEPTOR; GENE; DROSOPHILA AB Smad proteins are a family of highly conserved, intracellular proteins that signal cellular responses downstream of transforming growth factor-beta (TGF-beta) family serine/threonine kinase receptors. One of these molecules, Smad4, originally identified as the candidate tumor suppressor gene dpc-4, reconstitutes TGF-beta- and activin-dependent transcriptional responses in Smad4 null cell lines and interacts in a ligand-dependent manner with other Smad family members in both TGF-beta, activin, and bone morphogenetic protein-2/-4 pathways. Here, we used an assay based on the restoration of ligand-dependent transcriptional responses in a Smad4 null cell line to characterize functional domain structures within Smad4. We showed that restoration of TGF-beta-induced transcriptional responses by Smad4 was inhibited by co-transfection with a kinase dead TGF-beta type II receptor and that constitutive activation was blocked with TGF-beta neutralizing antibodies, confirming the essential role of Smad4 in TGF-beta signaling. Using a series of Smad4 mutation, deletion, and Smad1/Smad4 chimera constructs we identified a 47-amino acid deletion within the middle-linker region of Smad4 that is essential for the mediation of signaling responses. In addition, we showed that the NH2-terminal domain of Smad4 augments ligand-dependent activation associated with the middle-linker region, indicating that there is a distinct ligand-response domain within the N terminus of this molecule. RP deCaestecker, MP (reprint author), NCI,CHEMOPREVENT LAB,NIH,BLDG 41,RM C629,41 LIB DR,MSC 5055,BETHESDA,MD 20892, USA. NR 25 TC 117 Z9 117 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 23 PY 1997 VL 272 IS 21 BP 13690 EP 13696 DI 10.1074/jbc.272.21.13690 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XA062 UT WOS:A1997XA06200035 PM 9153220 ER PT J AU Hollander, MC Zhan, QM Bae, I Fornace, AJ AF Hollander, MC Zhan, QM Bae, I Fornace, AJ TI Mammalian GADD34, an apoptosis- and DNA damage-inducible gene SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-SUPPRESSOR GENE; IMMEDIATE EARLY RESPONSE; P53-REGULATED PROTEIN; GROWTH ARREST; P53; CELLS; INDUCTION; CHECKPOINT; DIFFERENTIATION; NEUROBLASTOMA AB The mammalian cellular response to genotoxic stress is a complex process involving many known and probably many as yet unknown genes. Induction of the human DNA damage- and growth arrest-inducible gene, GADD34, by ionizing radiation was only seen in certain cell lines and correlated with apoptosis following ionizing radiation. In addition, the kinetics and dose response of GADD34 to ionizing radiation closely paralleled that of the apoptosis inhibitor, BAX. However, unlike BAX, the GADD34 response was independent of cellular p53 status. The carboxyl terminus of GADD34 has homology with the carboxyl termini of two viral proteins, one of which is known to prevent apoptosis of virus infected cells. The association of GADD34 expression with certain types of apoptosis and its homology with a known apoptosis regulator suggests that GADD34 may play a role in apoptosis as well. C1 SAMYANG GENEX RES INST,TAEJON 305348,SOUTH KOREA. RP Hollander, MC (reprint author), NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892, USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 44 TC 120 Z9 123 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 23 PY 1997 VL 272 IS 21 BP 13731 EP 13737 DI 10.1074/jbc.272.21.13731 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XA062 UT WOS:A1997XA06200041 PM 9153226 ER PT J AU Hsu, YT Youle, RJ AF Hsu, YT Youle, RJ TI Nonionic detergents induce dimerization among members of the Bcl-2 family SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ROD PHOTORECEPTOR CELLS; GATED CHANNEL; PROTEIN; DEATH; BAX; BCL-X(L); CLONING; HETERODIMERIZATION; TRANSLOCATION; MITOCHONDRIA AB Members of the Bcl-2 family (including Bcl-2, Bcl-X-L, and Bax) play key roles in the regulation of apoptosis. These proteins are believed to be membrane-associated and have been proposed to regulate apoptosis through both homodimerization and heterodimerization. We have found that whereas Bcl-2 is predominantly membrane-associated as previously reported, significant amounts of Bcl-X-L and most of the Bax proteins are not membrane-associated and thus appear in the cytosolic fraction of thymocyte and splenocyte extracts, This finding allows the study of the dimerization properties and conformation of these proteins in the absence of detergent perturbation. For this analysis, we have produced monoclonal antibodies that are specific for known epitopes of Bax, Bcl-2, and Bcl-X-L. An antibody to an N-terminal epitope (alpha uBax 6A7) between amino acids 12 and 24 fails to bind the soluble cytosolic form of Bax, indicating that this epitope is normally buried. Nonionic detergents alter the fax conformation to expose this epitope. In the presence of nonionic detergent, the 6A7 antibody avidly binds the monomeric form of fax, but not Bax complexed with either Bcl-X, or Bcl-2. In contrast, a monoclonal antibody to an adjacent epitope of Bax (alpha mBax 5B7) within amino acids 3-16 binds the soluble and detergent-altered forms of fax and also binds the Bax.Bcl-X-L or the Bax.Bcl-2 complex. Surprisingly, in the absence of detergent Bax fails to form homodimers or heterodimers with Bcl-X-L. These results demonstrate a novel conformational state of members of the Bcl-2 family under a physiological condition that is distinct from the detergent-altered state that forms dimers and is currently believed to regulate apoptosis. C1 NINCDS, BIOCHEM SECT, SURG NEUROL BRANCH, NIH, BETHESDA, MD 20892 USA. NR 30 TC 444 Z9 449 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 23 PY 1997 VL 272 IS 21 BP 13829 EP 13834 DI 10.1074/jbc.272.21.13829 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XA062 UT WOS:A1997XA06200055 PM 9153240 ER PT J AU Krah, R ODea, MH Gellert, M AF Krah, R ODea, MH Gellert, M TI Reverse gyrase from Methanopyrus kandleri - Reconstitution of an active extremozyme from its two recombinant subunits SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID I TOPOISOMERASE; ATP; SULFOLOBUS; EXPRESSION; CLEAVAGE; INVITRO; BINDING AB Reverse gyrases are ATP-dependent type I 5'-topoisomerases that positively supercoil DNA. Reverse gyrase from Methanopyrus kandleri is unique as the first heterodimeric type I 5'-topoisomerase described, con sisting of a 138-kDa subunit involved in the hydrolysis of ATP (RgyB) and a 43-kDa subunit that forms the covalent complex with DNA during the topoisomerase reaction (RgyA). Here we report the reconstitution of active reverse gyrase from the two recombinant proteins overexpressed in Escherichia coli. Both proteins have been purified by column chromatography to >90% homogeneity. RgyB has a DNA-dependent ATPase activity at high temperature (80 degrees C) and is independent of the presence of RgyA RgyA alone has no detectable activity. The addition of RgyA to RgyB reconstitutes positive supercoiling activity, but the RgyB and RgyA subunits form a stable heterodimer only after being heated together. This is the first case in which it has been possible to reconstitute an active heterodimeric enzyme of a hyperthermophilic prokaryote from recombinant proteins. C1 NIDDK,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 21 TC 18 Z9 18 U1 2 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 23 PY 1997 VL 272 IS 21 BP 13986 EP 13990 DI 10.1074/jbc.272.21.13986 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XA062 UT WOS:A1997XA06200078 PM 9153263 ER PT J AU Kimura, T Sakamoto, H Appella, E Siraganian, RP AF Kimura, T Sakamoto, H Appella, E Siraganian, RP TI The negative signaling molecule SH2 domain-containing inositol-polyphosphate 5-phosphatase (SHIP) binds to the tyrosine-phosphorylated beta subunit of the high affinity IgE receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL ANTIGEN RECEPTOR; BASOPHILIC LEUKEMIA-CELLS; FC-GAMMA-RIIB; T-CELL; HISTAMINE-RELEASE; MAST-CELLS; ZETA-CHAIN; PROTEIN; ACTIVATION; TRANSDUCTION AB The SH2 domain-containing inositol-polyphosphate 5-phosphatase, SHIP, associates with Fc gamma RIIB and negatively regulates both B-cell and mast cell function, We report here that SHIP was tyrosine phosphorylated after high affinity IgE receptor (Fc epsilon RI) aggregation in rat basophilic leukemia RBL-2H3 cells, The ty rosine phosphorylation of SHIP was an early event after receptor aggregation and was present in cells deficient in the protein-tyrosine kinase Syk, Furthermore it was not secondary to the increase of intracellular calcium or the activation of protein kinase C. SHIP was precipitated by immobilized phosphorylated synthetic peptides based on the immunoreceptor tyrosine-based activation motif (ITAM) of the beta but not the gamma subunit of the high affinity IgE receptor. Tyrosine phosphorylation of SHIP and its association with the tyrosine-phosphorylated beta subunit of Fc epsilon RI could play an important role in down-regulating receptor-mediated signal transduction in mast cells, Thus, whereas the activation molecule Syk associates with the gamma subunit ITAM, the beta subunit ITAM binds the negative signaling molecule SHIP. Therefore, unlike B cells where the antigen receptor and coreceptors such as Fc gamma RIIB or CD22 each recruits molecules with opposite effects, the Fc epsilon RI contains subunits which recruit molecules that activate and inhibit signal transduction. C1 NCI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. RP Kimura, T (reprint author), NIDR,IMMUNOL LAB,NIH,BLDG 10,RM 1N106,BETHESDA,MD 20892, USA. RI Sakamoto, Hiroshi/A-3181-2011 NR 45 TC 116 Z9 117 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 MAY 23 PY 1997 VL 272 IS 21 BP 13991 EP 13996 DI 10.1074/jbc.272.21.13991 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XA062 UT WOS:A1997XA06200079 PM 9153264 ER PT J AU Carson, JR Carmosin, RJ Pitis, PM Vaught, JL Almond, HR Stables, JP Wolf, HH Swinyard, EA White, HS AF Carson, JR Carmosin, RJ Pitis, PM Vaught, JL Almond, HR Stables, JP Wolf, HH Swinyard, EA White, HS TI Aroyl(aminoacyl)pyrroles, a new class of anticonvulsant agents SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ENAMINONES AB 2-Aroyl-4-(omega-aminoacyl)-(4) and 4-aroyl-2-(omega-aminoacyl)pyrroles (9) represent a new, structurally novel class of anticonvulsant agents. Compounds of type 4 were prepared by Friedel-Crafts acylation of a 2-aroylpyrrole with an omega-chloroacyl chloride followed by displacement of the chloro group by a primary or secondary amine. Compounds of type 9 were prepared by Friedel-Crafts aroylation of a 2-(omega-chloroacyl)pyrrole followed by displacement by an amine. These compounds were active in the mouse and rat maximal electroshock tests but not in the mouse metrazole test. The lead compound, RWJ-37868, 2-(4-chlorobenzoyl)-4-(1-piperidinylacetyl)-1,3,5-trimethylpyrrole (4d), showed potency and therapeutic index comparable to those of phenytoin and carbamazepine and greater than those of sodium valproate. This compound blocked bicuculline induced seizures, did not elevate seizure threshold following iv infusion of metrazole, and blocked influx of Ca2+ ions into cerebellar granule cells induced by K+ or veratridine. C1 NINCDS,EPILEPSY BRANCH,NATL INST HLTH,BETHESDA,MD 20892. UNIV UTAH,ANTICONVULSANT SCREENING PROJECT,DEPT PHARMACOL & TOXICOL,SALT LAKE CITY,UT 84108. RP Carson, JR (reprint author), RW JOHNSON PHARMACEUT RES INST,SPRING HOUSE,PA 19477, USA. NR 24 TC 36 Z9 37 U1 0 U2 4 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 MAY 23 PY 1997 VL 40 IS 11 BP 1578 EP 1584 DI 10.1021/jm9606655 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA XB655 UT WOS:A1997XB65500004 PM 9171868 ER PT J AU KupczykSubotkowska, L Siahaan, TJ Basile, AS Friedman, HS Higgins, PE Song, D Gallo, JM AF KupczykSubotkowska, L Siahaan, TJ Basile, AS Friedman, HS Higgins, PE Song, D Gallo, JM TI Modulation of melphalan resistance in glioma cells with a peripheral benzodiazepine receptor ligand melphalan conjugate SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID BRAIN-TUMORS; RHABDOMYOSARCOMA XENOGRAFT; RECURRENT GLIOMAS; BINDING-SITES; ASSAY; RAT; CHEMOTHERAPY; LOCALIZATION; GLUTATHIONE; DEPLETION AB Peripheral benzodiazepine receptors (PBRs) are located on the outer membrane of mitochondria, and their density is increased in brain tumors. Thus, they may serve as a unique intracellular and selective target for antineoplastic agents. A PBR ligand-melphalan conjugate (PBR-MEL) was synthesized and evaluated for cytotoxicity and affinity for PBRs. PBR-MEL (9) (i.e., 670 amu) was synthesized by coupling of two key intermediates: 4-[bis(2-chloroethyl)amino]-L-phenylalanine ethyl ester trifluoroacetate (6) and 1-(3'-carboxylpropyl)-7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one (8). On the basis of receptor-binding displacement assays in rat brain and glioma cells, 9 had appreciable binding affinity and displaced a prototypical PBR ligand, Ro 5-4864, with IC50 values between 289 and 390 nM. 9 displayed differential cytotoxicity to a variety of rat and human brain tumor cell lines. In some of the cell lines tested including rat and human melphalan-resistant cell lines, 9 demonstrated appreciable cytotoxicity with IC50 values in the micromolar range, lower than that of melphalan alone. The enhanced activity of 9 may reflect increased membrane permeability, increased intracellular retention, or modulation of melphalan's mechanisms of resistance. The combined data support additional studies to determine how 9 may modulate melphalan resistance, its mechanisms of action, and if target selectivity can be achieved in in vivo glioma models. C1 FOX CHASE CANC CTR,DEPT MED ONCOL,PHILADELPHIA,PA 19111. UNIV KANSAS,DEPT PHARMACEUT CHEM,SIMONS LABS,LAWRENCE,KS 66047. NIDDK,NEUROSCI LAB,NATL INST HLTH,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT PEDIAT,DURHAM,NC 27710. NR 29 TC 33 Z9 33 U1 0 U2 3 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 MAY 23 PY 1997 VL 40 IS 11 BP 1726 EP 1730 DI 10.1021/jm960592p PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA XB655 UT WOS:A1997XB65500018 PM 9171882 ER PT J AU Agarwal, RP Olivero, OA AF Agarwal, RP Olivero, OA TI Genotoxicity and mitochondrial damage in human lymphocytic cells chronically exposed to 3'-azido-2',3'-dideoxythymidine SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE mitochondrium; mitochondrial DNA; nucleoside analog ID HUMAN-IMMUNODEFICIENCY-VIRUS; BONE-MARROW-CELLS; REVERSE-TRANSCRIPTASE; PREFERENTIAL INCORPORATION; NUCLEOSIDE ANALOGS; ZIDOVUDINE THERAPY; DNA-POLYMERASES; CELLULAR DNA; IN-VITRO; AZT AB AZT (3'-azido-2',3'-dideoxythymidine), the first nucleoside analog approved for the treatment of AIDS (acquired immunodeficiency syndrome), induces significant toxic effects in humans exposed to therapeutic doses. As an inhibitor of the HIV-1 (human immunodeficiency virus 1) reverse transcriptase, AZT blocks the incorporation of nucleotides into the host's newly synthesized DNA. Incorporation of AZT into mammalian DNA as well as specific localization of the drug into telomeric DNA, has been previously documented by immunohistochemistry. As with other nucleoside analogs, AZT has affinity for polymerase-gamma, the enzyme responsible for the replication of mitochondrial DNA. In order to examine the mechanisms of toxic events induced by long-term AZT exposure, human T-lymphocytic H-9 cells were cultured with 25 mu M AZT for 7 months. In the resulting H9-AZT cells, incorporation of AZT into DNA was demonstrated by radioimmunoassay and immunohistochemistry, chromosomal aberrations and micronuclei were scored and intracellular lipid distribution was determined. Two pmol of AZT per microgram of DNA were detected by radioimmunoassay in H9-AZT cells. Control cells showed negative values in the radioimmunoassay. Cytogenetic observations on H9-AZT cells showed an increase in chromosomal aberrations and nuclear fragmentation when compared with unexposed H-9 cells. Electron microscopy revealed mitochondrial damage and an elevated accumulation of neutral intracellular lipid deposits probably as a consequence of a distortion in the beta-oxidation of fatty acids normally carried out by this organelle. The toxicities explored here suggest that the mechanisms of AZT induced cytotoxicity in bone marrow of the patients chronically exposed to the drug in vivo may involve both chromosomal and mitochondrial DNA damage. C1 NCI,NIH,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. UNIV MIAMI,SCH MED,MIAMI,FL 33136. FU NIAID NIH HHS [AI 29155] NR 36 TC 44 Z9 44 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD MAY 23 PY 1997 VL 390 IS 3 BP 223 EP 231 DI 10.1016/S1383-5718(97)00014-4 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA XB566 UT WOS:A1997XB56600004 PM 9186571 ER PT J AU Appella, DH Christianson, LA Klein, DA Powell, DR Huang, XL Barchi, JJ Gellman, SH AF Appella, DH Christianson, LA Klein, DA Powell, DR Huang, XL Barchi, JJ Gellman, SH TI Residue-based control of helix shape in beta-peptide oligomers SO NATURE LA English DT Article ID SECONDARY STRUCTURE; PROGRAM; POLY(ALPHA-ISOBUTYL-L-ASPARTATE); DERIVATIVES; POLYAMIDE; ACID AB Proteins and RNA are unique among known polymers in their ability to adopt compact and well-defined folding patterns. These two biopolymers can perform complex chemical operations such as catalysis and highly selective recognition, and these functions are linked to folding in that the creation of an active site requires proper juxtaposition of reactive groups. So the development of new types of polymeric backbones with well-defined and predictable folding propensities ('foldamers') might lead to molecules with useful functions(1,2). The first step in foldamer development is to identify synthetic oligomers with specific secondary structural preferences(3-13). Whereas alpha-amino acids can adopt the well-known alpha-helical motif of proteins, it was shown recently(11-13) that beta-peptides(3) constructed from carefully chosen beta-amino acids can adopt a different, stable helical conformation defined by interwoven 14-membered-ring hydrogen bonds (a 14-helix; Fig. 1a). Here we report that beta-amino acids can also be used to design beta-peptides with a very different secondary structure, a 12-helix (Fig. 1a). This demonstrates that by altering the nature of beta-peptide residues, one can exert rational control over the secondary structure. C1 NCI,MED CHEM LAB,DIV BASIC SCI,BETHESDA,MD 20892. UNIV WISCONSIN,DEPT CHEM,MADISON,WI 53706. RI Barchi Jr., Joseph/N-3784-2014 NR 30 TC 452 Z9 453 U1 7 U2 88 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD MAY 22 PY 1997 VL 387 IS 6631 BP 381 EP 384 DI 10.1038/387381a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XA496 UT WOS:A1997XA49600054 PM 9163422 ER PT J AU Jacobson, JM Greenspan, JS Spritzler, J Ketter, N Fahey, JL Jackson, JB Fox, L Chernoff, M Wu, AW MacPhail, LA Vasquez, GJ Wohl, DA AF Jacobson, JM Greenspan, JS Spritzler, J Ketter, N Fahey, JL Jackson, JB Fox, L Chernoff, M Wu, AW MacPhail, LA Vasquez, GJ Wohl, DA TI Thalidomide for the treatment of oral aphthous ulcers in patients with human immunodeficiency virus infection SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA PRODUCTION; GIANT MUCOCUTANEOUS APHTHAE; ERYTHEMA-NODOSUM LEPROSUM; HIV-INFECTION; OROGENITAL ULCERATION; SOLUBLE RECEPTORS; TYPE-1 INFECTION; RECURRENT; AIDS AB Background In patients with advanced human immunodeficiency virus (HIV) infection, aphthous ulceration of the mouth and oropharynx can become extensive and debilitating. Preliminary reports suggest that thalidomide may promote the healing of oral aphthous ulcers. Methods We performed a double-blind, randomized, placebo-controlled study of thalidomide as therapy for oral aphthous ulcers in HIV-infected patients. The patients received a four-week course of either 200 mg of thalidomide or placebo orally once per day. They were evaluated weekly for the condition of the ulcers, their quality of life, and evidence of toxicity. Assays were performed for plasma tumor necrosis factor alpha (TNF-alpha), soluble TNF-alpha receptors, and HIV RNA. Results Sixteen of 29 patients in the thalidomide group (55 percent) had complete healing of their aphthous ulcers after four weeks, as compared with only 2 of 28 patients in the placebo group (7 percent; odds ratio, 15; 95 percent confidence interval after adjustment for group sequential testing, 1.8 to 499; unadjusted P < 0.001). Pain diminished and the ability to eat improved with thalidomide treatment. The adverse effects noted with thalidomide included somnolence and rash (7 patients each), and 6 of the 29 patients discontinued treatment because of toxicity. Thalidomide treatment increased HIV RNA levels (median increase, 0.42 log(10) copies per milliliter; increase with placebo, 0.05; P = 0.04). With thalidomide treatment there were unexpected increases in the plasma concentrations of TNF-alpha and soluble TNF-alpha receptors. Conclusions Thalidomide is an effective treatment for aphthous ulceration of the mouth and oropharynx in patients with HIV infection. (C) 1997, Massachusetts Medical Society. C1 MT SINAI SCH MED,NEW YORK,NY. UNIV CALIF SAN FRANCISCO,DEPT STOMATOL,SAN FRANCISCO,CA 94143. HARVARD UNIV,SCH PUBL HLTH,STAT & DATA ANAL CTR,BOSTON,MA 02115. NIAID,DIV AIDS,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90024. JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. UNIV PUERTO RICO,SCH MED,DEPT MED,SAN JUAN,PR 00936. UNIV N CAROLINA,DEPT MED,CHAPEL HILL,NC. RP Jacobson, JM (reprint author), VET AFFAIRS MED CTR,DEPT MED,130 W KINGSBRIDGE RD,BRONX,NY 10468, USA. NR 44 TC 286 Z9 302 U1 4 U2 10 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 22 PY 1997 VL 336 IS 21 BP 1487 EP 1493 DI 10.1056/NEJM199705223362103 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA WZ767 UT WOS:A1997WZ76700003 PM 9154767 ER PT J AU Coia, GM Devenney, M White, PS Meyer, TJ Wink, DA AF Coia, GM Devenney, M White, PS Meyer, TJ Wink, DA TI Osmium hydrazido and dinitrogen complexes SO INORGANIC CHEMISTRY LA English DT Article ID COORDINATED NITRENE; NITROSYL COMPLEXES; NITROGEN-FIXATION; INTERMEDIATE; RUTHENIUM; AMMONIA; DERIVATIVES; REACTIVITY; OXIDATION; REDUCTION AB [Os(tpy)(bpy)(NH3)](PF6)(2) (1) was oxidized electrochemically in the presence of a series of amines in aqueous solutions buffered to pH 7. With secondary aliphatic amines, electrolysis gave [Os(tpy)(bpy)(NNR2)](PF6)(3) (3); number of electrons n = 4.6-5.0, 3 was reduced to [Os(tpy)(bpy)(NNR2)](PF6)(2) (2) in aqueous and nonaqueous solutions with n = 1.0, The structures of 2 were determined by X-ray crystallography for NR2 = diethylamide (2a) and morpholide (2c) and were found to exhibit bent hydrazido(2-) coordination (Os-N-N = 137 degrees), The salts crystallized in the triclinic system, space group P (1) over bar. For 2a, a = 9.004(1) Angstrom, b = 9.796(1) Angstrom, c = 20.710(2) Angstrom, alpha = 88.78(2)degrees, beta = 85.43(2)degrees, gamma = 86.22(2)degrees, and Z = 2. For 2c, a = 9.632(8) Angstrom, b = 21.229(9) Angstrom, c 9.039(5) Angstrom, alpha = 97.41(4)degrees, beta = 94.28(5)degrees, gamma = 85.07(5)degrees, and Z = 2. Solutions of 2 were protonated in strongly acidic media to give hydrazido(1-) complexes. The pK(a) of the protonated form of 2a is 0.90 +/- 0.01. Reduction of 2 in aqueous solutions of pH < gave 1 and NH2R2+ with n = 4.0. At higher pH, there is evidence for an Os(II) hydrazine intermediate. Oxidation of 3 by one electron afforded transiently stable species which decomposed to give [Os(tpy)(bpy)(NCCH3)](3+) in acetonitrile solution. Pseudo-first-order rate constants of 8.1 +/- 0.9 s(-1) and 0.200 +/- .005 s(-1) were estimated by cyclic voltammetry on solutions of 2a and 2b (NR2 = piperidide), respectively, Oxidation of 1 at pH 7, in the presence of primary aliphatic amines or ammonia, occurred with n = 5.9-6.2, and generated [Os-II(tpy)(bpy)(N-2)](PF6)(2) (4). C1 UNIV N CAROLINA,DEPT CHEM,VENABLE & KENAN LABS,CHAPEL HILL,NC 27599. NCI,FREDERICK CANC RES & DEV CTR,CHEM SECT,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 35 TC 26 Z9 26 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0020-1669 J9 INORG CHEM JI Inorg. Chem. PD MAY 21 PY 1997 VL 36 IS 11 BP 2341 EP 2351 DI 10.1021/ic961025v PG 11 WC Chemistry, Inorganic & Nuclear SC Chemistry GA XA488 UT WOS:A1997XA48800018 ER PT J AU Whitcup, SM Fortin, E Nussenblatt, RB Polis, MA Muccioli, C Belfort, R AF Whitcup, SM Fortin, E Nussenblatt, RB Polis, MA Muccioli, C Belfort, R TI Therapeutic effect of combination antiretroviral therapy on cytomegalovirus retinitis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID PREVALENCE; VIRUS C1 NIAID,BETHESDA,MD 20892. SAO PAULO HOSP,SAO PAULO,BRAZIL. RP Whitcup, SM (reprint author), NEI,BETHESDA,MD 20892, USA. RI Belfort Jr, Rubens/E-2252-2012; Muccioli, Cristina/C-3419-2013 OI Belfort Jr, Rubens/0000-0002-8422-3898; NR 6 TC 96 Z9 98 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 21 PY 1997 VL 277 IS 19 BP 1519 EP 1520 DI 10.1001/jama.277.19.1519 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA WY969 UT WOS:A1997WY96900027 PM 9153364 ER PT J AU Lockshin, MD AF Lockshin, MD TI Antiphospholipid antibody - Babies, blood clots, biology SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ANTICARDIOLIPIN ANTIBODIES; PREDNISONE; THROMBOSIS C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,BETHESDA,MD 20892. NR 31 TC 51 Z9 52 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 21 PY 1997 VL 277 IS 19 BP 1549 EP 1551 DI 10.1001/jama.277.19.1549 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA WY969 UT WOS:A1997WY96900034 PM 9153370 ER PT J AU Goldstein, AM Tucker, MA AF Goldstein, AM Tucker, MA TI Screening for CDKN2A mutations in hereditary melanoma SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CUTANEOUS MALIGNANT-MELANOMA; KINASE-4 INHIBITOR GENE; FAMILIAL MELANOMA; CHROMOSOME 9P; HUMAN CANCERS; KINDREDS; HETEROGENEITY; PROGRESSION; DELETIONS; LINKAGE RP Goldstein, AM (reprint author), NCI,GENET EPIDEMIOL BRANCH,DIV CANC EPIDEMIOL & GENET,NIH,EXECUT PLAZA N,RM 439,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. RI Tucker, Margaret/B-4297-2015 NR 33 TC 39 Z9 39 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 21 PY 1997 VL 89 IS 10 BP 676 EP 678 DI 10.1093/jnci/89.10.676 PG 3 WC Oncology SC Oncology GA XA219 UT WOS:A1997XA21900001 PM 9168176 ER PT J AU Sander, M Ramotar, D AF Sander, M Ramotar, D TI Partial purification of Pde1 from Saccharomyces cerevisiae: Enzymatic redundancy for the repair of 3'-terminal DNA lesions and abasic sites in yeast SO BIOCHEMISTRY LA English DT Article ID APURINIC APYRIMIDINIC ENDONUCLEASE; STRUCTURAL GENE APN1; ESCHERICHIA-COLI; NUCLEASE ACTIVITY; EXCISION-REPAIR; EXONUCLEASE-III; HOMOLOGY; CLONING; DAMAGE; IV AB Earlier work indicates that the major DNA repair phosphodiesterase (PDE) in yeast cells is the well-characterized Apn1 protein. Apn1 demonstrates both Mg2+-independent PDE activity and Mg2+ independent class II apurinic/apyrimidinic (AP) endonuclease activity and represents greater than 90% of the activity detected in crude extracts from wild-type yeast cells. Apn1 is related to Echerichia coli endonuclease IV, both in its enzymatic properties and its amino acid sequence. In this work, we report the partial purification of a novel yeast protein, Pde1, present in Apn1-deficient cells. Pde1 is purified by sequential BioRex-70, PBE118, and MonoS chromatography steps using a sensitive and highly specific 3'-phosphoglycolate-terminated oligonucleotide-based assay as a measure of PDE activity. Mg2+-stimulated PDE and Mg2+-stimulated class II AP endonuclease copurify during this procedure. These results indicate that yeast, like many other organisms studied to date, has enzymatic redundancy for the repair of 3'-blocking groups and abasic sites. C1 UNIV MONTREAL,MAISON ROSEMONT HOSP,RES CTR,MONTREAL,PQ H1T 2M4,CANADA. RP Sander, M (reprint author), NIEHS,MOL GENET LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 32 TC 25 Z9 25 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 MAY 20 PY 1997 VL 36 IS 20 BP 6100 EP 6106 DI 10.1021/bi970048y PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XA274 UT WOS:A1997XA27400020 PM 9166780 ER PT J AU Wu, JQ Maki, AH Ozarowski, A Urbaneja, MA Henderson, LE CasasFinet, JR AF Wu, JQ Maki, AH Ozarowski, A Urbaneja, MA Henderson, LE CasasFinet, JR TI Fluorescence, phosphorescence, and optically detected magnetic resonance studies of the nucleic acid association of the nucleocapsid protein of the murine leukemia virus SO BIOCHEMISTRY LA English DT Article ID SINGLE-STRANDED POLYNUCLEOTIDES; DNA-BINDING-PROTEINS; TRYPTOPHAN RESIDUES; ZINC FINGERS; STACKING INTERACTIONS; POLY(DEOXYTHYMIDYLIC) ACID; REVERSE-TRANSCRIPTASE; ANNEALING ACTIVITIES; VIRAL-RNA; HIV-1 AB Fluorescence, phosphorescence, and optical detection of triplet state magnetic resonance (ODMR) are employed to investigate the interaction of p10, the nucleocapsid protein of the Moloney murine leukemia virus, with nucleic acids, p10 is a 55-amino acid protein containing a single zinc finger motif, (CCHC39)-C-26-H-29-C-34, that includes Y at position 28 and W at position 35. In addition, the interactions of a zinc finger peptide, p10-ZF, comprising residues 24-41 of p10, and a doubly mutated 24-41 peptide, p10-ZF' in which the positions of Y and W are interchanged, also are reported, The measurements focus on the direct involvement of the sole W residue in the nucleic acid interaction. Fluorescence quenching and salt-back titrations indicate complex formation of p10 with several octanucleotides-(dT)g, (dI)g, (dU)-dT, and (5-BrdU)(7)dT-and with the polynucleotides poly(dT) and poly(dI). Poly(dI) binds with the highest affinity. Apparent binding constants and salt-back midpoints are reported. Neither p10-ZF nor p10-ZF' exhibits significant fluorescence quenching by these DNA substrates. Binding of p10-ZF to fluorescent poly(ethenoadenylic acid) was detected with greatly reduced affinity relative to p10, but binding of p10-ZF' was undetectable, These results are in general agreement with phosphorescence and ODMR measurements monitoring W, Addition of poly(I) to p10 leads to a phosphorescence red shift, reduction in the zero-field splitting (ZFS) parameters D and E, and a significantly reduced phosphorescence lifetime, each consistent with aromatic stacking interactions between W and the nucleobases. These effects are smaller with p10-ZF and undetectable with p10-ZF'. Poly(U) produces no significant changes in the triplet state parameters of W; no stacking interactions are observed even for p10, (5-BrdU)(7)dT yields large phosphorescence red shifts in p10 and p10-ZF, and reductions of D, but no significant heavy atom effects. These effects probably are due to enhanced local polarizability caused by Br, but any stacking interactions in these complexes would exclude van der Waals contacts between W and the Br atoms. C1 UNIV CALIF DAVIS,DEPT CHEM,DAVIS,CA 95616. NCI,FREDERICK CANC RES & DEV CTR,AIDS VACCINE PROGRAM,SAIC,FREDERICK,MD 21702. FU NIEHS NIH HHS [ES-02662] NR 59 TC 7 Z9 7 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 20 PY 1997 VL 36 IS 20 BP 6115 EP 6123 DI 10.1021/bi962951o PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XA274 UT WOS:A1997XA27400022 PM 9166782 ER PT J AU Fritsch, M Anderson, I Leary, CM Gorski, J AF Fritsch, M Anderson, I Leary, CM Gorski, J TI Two populations of the estrogen receptor separated and characterized using aqueous two-phase partitioning SO BIOCHEMISTRY LA English DT Article ID STEROID-BINDING DOMAIN; HEAT-SHOCK PROTEIN; HUMAN-SERUM ALBUMIN; DNA RESPONSE ELEMENT; GLUCOCORTICOID RECEPTOR; HORMONE ACTION; INTERCONVERSION MODEL; PROGESTERONE-RECEPTOR; POLY(ETHYLENE GLYCOL); MEDIATED CONVERSION AB TWO populations of the rat uterine estrogen receptor (ER) were separated and characterized using aqueous two-phase partitioning. Countercurrent distribution of rat uterine cytosolic ER allowed rapid and efficient separation of two populations, one population partitioned preferentially into the top phase (T, K-obs = 3-6) and the other into the bottom phase (B, K-obs = 0.01-0.03) The majority of unoccupied cytosolic ER is in the T population. Upon estrogen binding and/or heating to 30 degrees C in vitro the T population is converted to the B population. The transition from T to B does not exclusively involve loss of heat shock protein 90 and does not alter the ligand binding ability of the steroid binding domain. Using the human ER steroid binding domain overproduced in Escherichia coli and the steroid binding domain generated by partial trypsinization of the rat uterine ER, we demonstrate that the characteristic distinguishing T and B populations is not localized to this domain alone but may be associated with the amino terminal half of the ER (the A/B and DNA binding domains). The T to B transition of the ER also occurs in human MCF-7 breast cancer cells upon treatment with estrogen at 37 degrees C. C1 UNIV WISCONSIN,DEPT BIOCHEM,MADISON,WI 53706. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. FU NICHD NIH HHS [HD08192, HD07259] NR 70 TC 2 Z9 2 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 MAY 20 PY 1997 VL 36 IS 20 BP 6230 EP 6242 DI 10.1021/bi962629d PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XA274 UT WOS:A1997XA27400036 PM 9166796 ER PT J AU Beckner, ME Krutzsch, HC Tsokos, M Moul, DE Liotta, LA AF Beckner, ME Krutzsch, HC Tsokos, M Moul, DE Liotta, LA TI The aggregated form of an AAMP derived peptide behaves as a heparin sensitive cell binding agent SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE AAMP peptide; cell adhesion; cell immobilization; heparin binding; biocompatible material; peptide mapping ID HUMAN-MELANOMA CELLS; CARDIOPULMONARY BYPASS; PROTEOGLYCAN; ADHESION AB A peptide termed P189, derived from the sequence of a newly discovered protein, AAMP (angio-associated migratory cell protein), contains a motif that is predicted to bind heparin. It occurs near the amino terminal end of AAMP. Previous studies have shown that in its solubilized form P189 (RRLRRMESESES) binds heparin and melanoma cells. The peptide is bipolar in that it contains positive charges at its amino end and negative charges at its carboxyl end. It forms strongly aggregated particles that require exposure to 50% DMSO and 100 degrees C for solubilization to occur. Now heparin and cell binding (heparin sensitive) are also demonstrated for the peptide in its particulate form. Cell binding/clustering to the peptide particles is strong and resists exposure to various reagents (sugars and inhibitors of glycolysis and protein synthesis) except heparin. Tumor cell migration is partially inhibited by the presence of the peptide. On electron photomicrographs the peptide is seen in close apposition to cell membranes. Heparin sensitivity of the cell binding indicates that cell surface glycosaminoglycans are involved. The aggregated peptide binds heparin in a saturable manner with a dissociation constant, K-d, of 306 pmol. Cell binding/clustering studies using peptide variants of P189, which have substitutions in either the charged and/or nonpolar residues, show that the specific sequence of P189 optimizes heparin-sensitive cell aggregation. (C) 1997 John Wiley & Sons. Inc. C1 NIMH,DIV EPIDEMIOL & SERV RES,NIH,BETHESDA,MD 20892. RP Beckner, ME (reprint author), NCI,PATHOL LAB,NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 17 TC 2 Z9 2 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD MAY 20 PY 1997 VL 54 IS 4 BP 365 EP 372 DI 10.1002/(SICI)1097-0290(19970520)54:4<365::AID-BIT10>3.0.CO;2-F PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA WW140 UT WOS:A1997WW14000010 PM 18634104 ER PT J AU Fenjves, ES Schwartz, PM Blaese, RM Taichman, LB AF Fenjves, ES Schwartz, PM Blaese, RM Taichman, LB TI Keratinocyte gene therapy for adenosine deaminase deficiency: A model approach for inherited metabolic disorders SO HUMAN GENE THERAPY LA English DT Article ID EPIDERMAL-KERATINOCYTES; BONE-MARROW; CELLS; RETROVIRUS; EXPRESSION; IMMUNODEFICIENCY; FIBROBLASTS; SEPARATION; PROTEINS; ENZYME AB Disorders in which there is toxic buildup of circulating substrate may be treated by furnishing an enzyme reservoir capable of metabolically processing the excess substrate. The epidermal keratinocyte is a potential site for such a reservoir, In this study, we explore the capacity of genetically modified keratinocytes to metabolize extracellular substrate in a culture model that resembles in vivo epidermal architecture, Keratinocytes from adenosine deaminase (ADA)-deficient patients were transduced with a retroviral vector encoding the human ADA gene and the capacity of this tissue to deaminate deoxyadenosine (dAdo) in vitro was measured. The results show that at a substrate concentration of 10 mu M, ADA-corrected keratinocytes deaminate dAdo at a rate of 0.38 nmol/min.10(6) cells. These results indicate that keratinocytes process extracellular substrate at rates that suggest complete substrate conversion in a single pass, This study provides a strong indication that the epidermis, the largest and most accessible tissue of the body, is a valuable site for designing clinically relevant gene therapies. C1 VET AFFAIRS MED CTR,DEPT DERMATOL,W HAVEN,CT. YALE UNIV,NEW HAVEN,CT 06516. NATL INST HLTH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP Fenjves, ES (reprint author), SUNY STONY BROOK,DEPT ORAL BIOL & PATHOL,STONY BROOK,NY 11794, USA. FU NIDCR NIH HHS [R37-DEO4511]; PHS HHS [R01-49093] NR 39 TC 26 Z9 27 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 MAY 20 PY 1997 VL 8 IS 8 BP 911 EP 917 DI 10.1089/hum.1997.8.8-911 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA XC072 UT WOS:A1997XC07200003 PM 9195213 ER PT J AU Smith, MR Wilson, ML Hamanaka, R Chase, D Kung, HF Longo, DL Ferris, DK AF Smith, MR Wilson, ML Hamanaka, R Chase, D Kung, HF Longo, DL Ferris, DK TI Malignant transformation of mammalian cells initiated by constitutive expression of the polo-like kinase SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROTEIN-KINASE; DROSOPHILA POLO; PHOSPHOLIPASE-C; CYCLE CONTROL; PHOSPHATASE; IDENTIFICATION; ACTIVATION; SPINDLE; GENE; PLK AB Polo-like kinase (Plk) is the mammalian homologue of the Drosophila polo and Saccharomyces cerevisiae CDC5 genes, which are thought to be involved in regulating chromosomal segregation. Previously, we showed that transient ectopic expression of Plk could induce DNA synthesis in quiescent NIH 3T3 cells, suggesting that Plk might also have a function during G(1) or S phase, Here we report that microinjection of Plk mRNA is sufficient to drive quiescent cells into mitosis and that constitutive expression of Plk in NIH 3T3 cells causes oncogenic focus formation. These transformed cells grow in soft agar and form tumors in nude mice. Because Plk expression has been shown to be high in various human tumors, we suggest that Plk may contribute to the promotion and/or progression of human cancers. (C) 1997 Academic Press. C1 UNIV CALIF SAN DIEGO,GRAD PROGRAM BIOMED SCI,SAN DIEGO,CA 92093. OITA MED UNIV,DEPT BIOCHEM,OITA 8791706,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,NIA,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,LAB BIOCHEM PHYSIOL,DIV BASIC SCI,FREDERICK,MD 21702. NIA,NIH,BALTIMORE,MD 21224. RP Smith, MR (reprint author), NCI,FREDERICK CANC RES & DEV CTR,INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,FREDERICK,MD 21702, USA. NR 39 TC 200 Z9 213 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 MAY 19 PY 1997 VL 234 IS 2 BP 397 EP 405 DI 10.1006/bbrc.1997.6633 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XB331 UT WOS:A1997XB33100024 PM 9177283 ER PT J AU Zhang, J Kovac, P AF Zhang, J Kovac, P TI Synthesis of methyl alpha-glycosides of some higher oligosaccharide fragments of the O-antigen of Vibrio cholerae O1, serotype Inaba and Ogawa SO CARBOHYDRATE RESEARCH LA English DT Article DE Vibrio cholerae O1; 2,4-O-benzylidene-3-deoxy-L-glycero-tetronic acid; N-iodosuccinimide silver triflate-promoted glycosylation; synthetic oligosaccharides ID C-13-NMR SPECTRA; BLOCK SYNTHESIS; REPEATING UNIT; POLYSACCHARIDE; DETERMINANTS; PENTASACCHARIDE; THIOGLYCOSIDE AB The title oligosaccharides, the tri- through the hexasaccharide in the Inaba series and the penta- and the hexasaccharide in the Ogawa series, have been synthesized using 1-thioglycosides of precursors to 3-O-benzyl-perosamine (4-amino-4,6-dideoxy-D-mannose) as building blocks and N-iodosuccinimide/silver triflate as a promoter. The azido groups in the assembled oligosaccharides were reduced to amino groups, which were then acylated using 2,4-O-benzylidene-3-deoxy-L-glycero-tetronic acid as the derivatizing reagent. Catalytic hydrogenolysis, simultaneously of the benzyl and benzylidene groups, gave the desired products that were characterized by H-1 and C-13 NMR spectroscopy. (C) 1997 Elsevier Science Ltd. C1 NIDDK,NIH,BETHESDA,MD 20892. NR 22 TC 26 Z9 26 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD MAY 19 PY 1997 VL 300 IS 4 BP 329 EP 339 DI 10.1016/S0008-6215(97)00070-0 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA XC864 UT WOS:A1997XC86400005 PM 9210300 ER PT J AU Freedman, DM Zahm, SH Dosemeci, M AF Freedman, DM Zahm, SH Dosemeci, M TI Residential and occupational exposure to sunlight and mortality from non-Hodgkin's lymphoma: Composite (threefold) case-control study SO BRITISH MEDICAL JOURNAL LA English DT Article ID WESTERN-CANADA-MELANOMA; MALIGNANT-MELANOMA; SUN EXPOSURE; SKIN-CANCER; SOCIOECONOMIC-STATUS; CUTANEOUS MELANOMA; UNITED-STATES; RISK-FACTORS AB Objective: To determine whether non-Hodgkin's lymphoma mortality is associated with sunlight exposure. Design: Three case-control studies based on death certificates of non-Hodgkin's lymphoma, melanoma, and skin cancer mortality examining associations with potential sunlight exposure from residence and occupation. Setting: 24 states in the United States. Subjects: All cases were deaths from non-Hodgkin's lymphoma, melanoma, and non-melanotic skin cancer between 1984 and 1991. Two age, sex, and race frequency matched controls per case were selected from non-cancer deaths. Main outcome measures: Odds ratios for non-Hodgkin's lymphoma, melanoma, and skin cancer from residential and occupational sunlight exposure adjusted for age, sex, race, socioeconomic status, and farming occupation. Results: Non-Hodgkin's lymphoma mortality was not positively associated with sunlight exposure based on residence. Both melanoma and skin cancer were positively associated with residential sunlight exposure. Adjusted odds ratios for residing in states with the highest sunlight exposure were 0.83 (95% confidence interval 0.81 to 0.86) for non-Hodgkin's lymphoma, 1.12 (1.06 to 1.19) for melanoma, and 1.30 (1.18 to 1.43) for skin cancer. In addition, non-Hodgkin's lymphoma mortality was not positively associated with occupational sunlight exposure (odds ratio 0.88; 0.81 to 0.96). Skin cancer was slightly positively associated with occupational sunlight exposure (1.14; 0.96 to 1.36). Conclusions: Unlike skin cancer and to some extent melanoma, non-Hodgkin's lymphoma mortality was not positively associated with exposure to sunlight The findings do not therefore support the hypothesis that sunlight exposure contributes to the rising rates of non-Hodgkin's lymphoma. C1 NCI,DIV CANC EPIDEMIOL & GENET,ROCKVILLE,MD 20892. RP Freedman, DM (reprint author), NCI,DIV CANC PREVENT & CONTROL,EPN-240J,ROCKVILLE,MD 20892, USA. RI Zahm, Shelia/B-5025-2015 NR 28 TC 73 Z9 74 U1 2 U2 3 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 MAY 17 PY 1997 VL 314 IS 7092 BP 1451 EP 1455 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA XA202 UT WOS:A1997XA20200022 PM 9167561 ER PT J AU Feinberg, M AF Feinberg, M TI Hidden dangers of incompletely suppressive antiretroviral therapy SO LANCET LA English DT Editorial Material RP Feinberg, M (reprint author), NIH,OFF AIDS RES,BETHESDA,MD 20892, USA. NR 7 TC 32 Z9 32 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 MAY 17 PY 1997 VL 349 IS 9063 BP 1408 EP 1409 DI 10.1016/S0140-6736(97)22020-9 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA WZ765 UT WOS:A1997WZ76500002 PM 9164310 ER PT J AU Brinkmann, U Webber, K DiCarlo, A Beers, R Chowdhury, P Chang, K Chaudhary, V Gallo, M Pastan, I AF Brinkmann, U Webber, K DiCarlo, A Beers, R Chowdhury, P Chang, K Chaudhary, V Gallo, M Pastan, I TI Cloning and expression of the recombinant FAb fragment of monoclonal antibody K1 that reacts with mesothelin present on mesotheliomas and ovarian cancers SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID SINGLE-CHAIN IMMUNOTOXINS; ESCHERICHIA-COLI; ANTIGEN CAK1; CELL-LINE; RENATURATION; CARCINOMA; PROTEINS; ANALOG; GENES; B3 AB The monoclonal antibody (MAb) KI recognizes an approximate 40 kDa glycoprotein, mesothelin, that is present on the surface of human mesothelial cells, mesotheliomas and ovarian cancers, We have cloned the cDNAs encoding the variable regions of MAb KI and constructed plasmids for expression of recombinant KI(FAb), Recombinant FAb was produced in Escherichia coli in inclusion bodies that were solubilized and refolded to active protein, Binding of KI MAb and FAb was compared by radioactive binding and competition assays and by surface plasmon resonance (BIAcore), Recombinant KI(FAb) binds to cells expressing KI-antigen with a similar affinity as papain derived FAb from KI(IgG) and with a 4- to 10-fold reduced affinity compared with bivalent IgG, The cloned FAb can be used to make higher affinity antibodies and immunoconjugates that could be useful for various types of immunotherapies. (C) 1997 Wiley-Liss, Inc. C1 NCI,MOL BIOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. US FDA,ROCKVILLE,MD 20857. UNIV DELHI,DEPT BIOCHEM,NEW DELHI,INDIA. NR 26 TC 12 Z9 12 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 16 PY 1997 VL 71 IS 4 BP 638 EP 644 PG 7 WC Oncology SC Oncology GA XB625 UT WOS:A1997XB62500021 PM 9178820 ER PT J AU Yao, LB Suzuki, H Ozawa, K Deng, JB Lehel, C Fukamachi, H Anderson, WB Kawakami, Y Kawakami, T AF Yao, LB Suzuki, H Ozawa, K Deng, JB Lehel, C Fukamachi, H Anderson, WB Kawakami, Y Kawakami, T TI Interactions between protein kinase C and pleckstrin homology domains - Inhibition by phosphatidylinositol 4,5-bisphosphate and phorbol 12-myristate 13-acetate SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID X-LINKED AGAMMAGLOBULINEMIA; BRUTON TYROSINE KINASE; BETA-GAMMA-SUBUNITS; ADRENERGIC-RECEPTOR KINASE; HETEROTRIMERIC G-PROTEINS; IMMUNODEFICIENT XID MICE; PH DOMAIN; SIGNALING PROTEINS; INOSITOL PHOSPHATES; HEMATOPOIETIC-CELLS AB Pleckstrin homology (PH) domains comprised of loosely conserved sequences of similar to 100 amino acid residues are a functional protein motif found in many signal-transducing and cytoskeletal proteins, Ne recently demonstrated that the PH domains of Tec family protein-tyrosine kinases Btk and Emt (equal to Itk and Tsk) interact with protein kinase C (PKC) and that PKC down regulates Btk by phosphorylation, In this study we have characterized the PKC-BtkPH domain interaction in detail, Using pure PKC preparations, it was shown that the Btk PH domain interacts with PRC with high affinity (K-D = 39 nM). Unlike other tested phospholipids, phosphatidylinositol 4,5-bisphosphate, which binds to several PH domains, competed with PKC for binding to the PH domain apparently because their binding sites on the amino-terminal portion of the PH domains overlap, The minimal PKC-binding sequence within the Btk PH domain was found to correspond roughly to the second and third beta-sheets of the PH domains of known tertiary structures, On the other hand, the C1 regulatory region of PKC epsilon containing the pseudosubstrate and zinc finger-like sequences was found to be sufficient for strong binding to the Btk PH domain, Phorbol 12-myristate 13-acetate (PMA), a potent activator of PKC that interacts with the C1 region of PHC, inhibited the PHC-PH domain interaction, whereas the bioinactive PMA (4-alpha-PMA) was ineffective, The zeta isoform of PKC, which has a single zinc finger-like motif instead of the two tandem zinc finger-like sequences present in conventional and novel PKC isoforms, does not bind PIMA. Thus, as expected, PH domain binding with PI(CS was not interfered with by PMA. Further, inhibitors that are known to attack the catalytic domains of serine/threonine kinases did not affect this PKC-PH domain interaction, In contrast, the presence of physiological concentrations of Ca2+ induced less than a 2-fold increase in PKC-PH domain binding, These results indicate that PKC binding to PH domains involve the beta 2-beta 3 region of the Btk PH domain and the C1 region of PKC, and agents that interact with either of these regions (i.e. phosphatidylinositol 4,5-bisphosphate binding to the PH domain and PMA binding to the C1 region of PKC) might act to regulate PKC-PH domain binding. C1 LA JOLLA INST ALLERGY & IMMUNOL,DIV ALLERGY,SAN DIEGO,CA 92121. KIRIN BREWERY CO LTD,PHARMACEUT RES LAB,TAKASAKI,GUMMA 37012,JAPAN. NCI,CELLULAR ONCOL LAB,NIH,BETHESDA,MD 20892. RI Kawakami, Toshiaki/O-1616-2015 FU NIAID NIH HHS [AI33617, AI38348] NR 54 TC 92 Z9 95 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 MAY 16 PY 1997 VL 272 IS 20 BP 13033 EP 13039 DI 10.1074/jbc.272.20.13033 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WZ384 UT WOS:A1997WZ38400026 PM 9148913 ER PT J AU Burshtyn, DN Yang, WT Yi, TL Long, EO AF Burshtyn, DN Yang, WT Yi, TL Long, EO TI A novel phosphotyrosine motif with a critical amino acid at position-2 for the SH2 domain-mediated activation of the tyrosine phosphatase SHP-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR RECEPTOR; BINDING-SPECIFICITY; CRYSTAL-STRUCTURES; SH-PTP2; BETA; PHOSPHOPEPTIDES; STIMULATION; PEPTIDES; AFFINITY AB SHP-1 is a protein-tyrosine phosphatase associated with inhibition of activation pathways in hematopoietic cells, The catalytic activity of SHP-1 is regulated by its two SH2 (Src homology 2) domains; phosphotyrosine peptides that bind to the SH2 domains activate SHP-1, The consensus sequence (I/V)XYXX(L/V) is present in the cytoplasmic tails of several lymphocyte receptors that interact with the second SH2 domain of SHP-1, In several of these receptors, there are two or three occurrences of the motif, Here we show that the conserved hydrophobic amino acid preceding the phosphotyrosine is critical for binding to and activation of SHP-1 by peptides corresponding to sequences from killer cell inhibitory receptors, The interaction of most SH2 domains with phosphopeptides requires only the phosphoty rosine and the three residues downstream of the tyrosine. In contrast, the shortest peptide able to bind or activate SHP-1 also included the two residues upstream of the phosphotyrosine, A biphosphopeptide corresponding to the cytoplasmic tail of a killer cell inhibitory receptor with the potential to interact simultaneously with both SH2 domains of SHP-1 was the most potent activator of SHP-1, The hydrophobic residue upstream of the tyrosine was also critical in the context of the biphosphopeptide, The contribution of a hydrophobic amino acid two residues upstream of the tyrosine in the SHP-1-binding motif may be an important feature that distinguishes inhibitory receptors from those that provide activation signals. C1 CLEVELAND CLIN FDN,RES INST,DEPT CANC BIOL,CLEVELAND,OH 44195. RP Burshtyn, DN (reprint author), NIAID,IMMUNOGENET LAB,NIH,TWINBROOK FACIL 2,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 34 TC 150 Z9 157 U1 2 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 16 PY 1997 VL 272 IS 20 BP 13066 EP 13072 DI 10.1074/jbc.272.20.13066 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WZ384 UT WOS:A1997WZ38400031 PM 9148918 ER PT J AU Gallo, RL Kim, KJ Bernfield, M Kozak, CA Zanetti, M Merluzzi, L Gennaro, R AF Gallo, RL Kim, KJ Bernfield, M Kozak, CA Zanetti, M Merluzzi, L Gennaro, R TI Identification of CRAMP, a cathelin-related antimicrobial peptide expressed in the embryonic and adult mouse SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ANTIBACTERIAL PEPTIDES; BOVINE NEUTROPHILS; CDNA SEQUENCE; BONE-MARROW; DEFENSINS; BACTENECINS; PROTEIN; FAMILY; PR-39; CELLS AB Cathelicidins are the precursors of potent antimicrobial peptides that have been identified in several mammalian species, Prior work has suggested that members of this gene family can participate in host defense through their antimicrobial effects and activate mesenchymal cells during wound repair, To permit further study of these proteins a reverse transcriptase-polymerase chain reaction approach was used to identify potential mouse homologs, A full-length 562-base pair cDNA clone was obtained encoding an NH2-terminal prepro domain homologous to other cathelicidins and a unique COOH-terminal peptide, This gene, named Cramp for cathelin-related antimicrobial peptide, was mapped to chromosome 9 at a region of conserved synteny to which genes for cathelicidins have been mapped in pig and man. Northern blot analysis detected a 1-kilobase transcript that was expressed in adult bone marrow and during embryogenesis as early as E12, the earliest stage of blood development, Reverse transcriptase-polymerase chain reaction also detected CRAMP expression in adult testis, spleen, stomach, and intestine but not in brain, liver, heart, or skeletal muscle. To evaluate further the expression and function of CRAMP a peptide corresponding to the predicted COOH-terminal region was synthesized, CD spectral analysis showed that CRAMP will form an amphipathic alpha-helix similar to other antimicrobial peptides, Functional studies showed CRAMP to be a potent antibiotic against Gram-negative bacteria by inhibiting growth of a variety of bacterial strains (minimum inhibitory concentrations 0.5-8.0 mu M) and by permeabilizing the inner membrane of Escherichia coli directly at 1 mu M. Antiserum against CRAMP revealed abundant expression in myeloid precursors and neutrophils, Thus, CRAMP represents the first antibiotic peptide found in cells of myeloid lineage in the mouse, These data suggest that inflammatory cells in the mouse can use a nonoxidative mechanism for microbial killing and permit use of the mouse to study the role such peptides play in host defense and wound repair. C1 HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02115. NIH,BETHESDA,MD 20892. UNIV UDINE,DEPT SCI & TECNOL BIOMED,I-33100 UDINE,ITALY. NATL LAB CONSORZIO INTERUNIV BIOTECHNOL,I-34012 TRIESTE,ITALY. RP Gallo, RL (reprint author), CHILDRENS HOSP,JOINT PROGRAM NEONATOL,300 LONGWOOD AVE,ENDERS 9,BOSTON,MA 02115, USA. RI Gallo, Richard/A-8931-2009 FU NIAMS NIH HHS [AR44379] NR 37 TC 237 Z9 243 U1 3 U2 11 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 16 PY 1997 VL 272 IS 20 BP 13088 EP 13093 DI 10.1074/jbc.272.20.13088 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WZ384 UT WOS:A1997WZ38400034 PM 9148921 ER PT J AU Kultz, D GarciaPerez, A Ferraris, JD Burg, MB AF Kultz, D GarciaPerez, A Ferraris, JD Burg, MB TI Distinct regulation of osmoprotective genes in yeast and mammals - Aldose reductase osmotic response element is induced independent of p38 and stress-activated protein kinase Jun N-terminal kinase in rabbit kidney cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAY; SACCHAROMYCES-CEREVISIAE; HEAT-SHOCK; DEHYDROGENASE; TRANSCRIPTION; CASCADE; BINDING; WATER AB In yeast glycerol-3-phosphate dehydrogenase 1 is essential for synthesis of the osmoprotectant glycerol and is osmotically regulated via the high osmolarity glycerol (HOG1) kinase pathway. Homologous protein kinases, p38, and stress-activated protein kinase/Jun N-terminal kinase (SAPK/JNK) are hyperosmotically activated in some mammalian cell lines and complement HOG1 in yeast, In the present study we asked whether p38 or SAPK/JNK signal synthesis of the osmoprotectant sorbi tol in rabbit renal medullary cells (PAP-HT25), analogous to the glycerol system in yeast, Sorbitol synthesis is catalyzed by aldose reductase (AR). Hyperosmolality increases AR transcription through an osmotic response element (ORE) in the 5'-flanking region of the AR gene, resulting in elevated sorbitol, We tested if AR-ORE is targeted by p38 or SAPK/JNK pathways in PAP-HT25 cells. Hyperosmolality (adding 150 nM NaCl) strongly induces phosphorylation of p38 and of c-Jun, a specific target of SAPK/JNK, Transient lipofection of a dominant negative mutant of SAPK kinase, SEK1-AL, into PAP-HT25 cells specifically inhibits hyperosmotically induced c-Jun phosphorylation, Transient Lipofection of a dominant negative p38 kinase mutant, MKK3-AL, into PAP-HT25 cells specifically suppresses hyperosmotic induction of p38 phosphorylation, We cotransfected either one of these mutants or their empty vector with an AR ORE luciferase reporter construct and compared the hyperosmotically induced increase in luciferase activity with that in cells lipofected with only the AR-ORE luciferase construct, Hyperosmolality increased luciferase activity equally (5-7-fold) under all conditions, We conclude that hyperosmolality induces p38 and SAPK/JNK cascades in mammalian renal cells, analogous to inducing the HOG1 cascade in yeast. However, activation of p38 or SAPK/JNK pathways is not necessary for transcriptional regulation of AR through the ORE. This finding stands in contrast to the requirement for the HOG1 pathway for hyperosmotically induced activation of yeast GPD1. RP Kultz, D (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,NIH,BLDG 9,RM 1N105,9 MEM DR,MSC 0951,BETHESDA,MD 20892, USA. NR 35 TC 82 Z9 82 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 MAY 16 PY 1997 VL 272 IS 20 BP 13165 EP 13170 DI 10.1074/jbc.272.20.13165 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WZ384 UT WOS:A1997WZ38400045 PM 9148932 ER PT J AU Powell, MD Ghosh, M Jacques, PS Howard, KJ LeGrice, SFJ Levin, JG AF Powell, MD Ghosh, M Jacques, PS Howard, KJ LeGrice, SFJ Levin, JG TI Alanine-scanning mutations in the ''primer grip'' of p66 HTV-1 reverse transcriptase result in selective loss of RNA priming activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; DNA-POLYMERASE; ESCHERICHIA-COLI; H ACTIVITIES; B-DNA; HIV-1; BINDING; TYPE-1; DOMAIN; MUTAGENESIS AB Alanine-scanning mutants of the primer grip region of human immunodeficiency virus type 1 reverse transcriptase were tested for their ability to extend RNA and DNA versions of the polypurine tract primer, and an oligonucleotide representing the 18-nucleotide sequence at the 3' end of tRNA(Lys3). A majority of the mutant enzymes were either completely or severely deficient in RNA priming activity, but, with only one exception, were able to efficiently extend DNA versions of the same primers, The mutant enzymes were able to bind to RNA primers, indicating that the defect in RNA priming was not simply a loss of binding activity, Mutations at positions 229, 233, and 235 dramatically reduced the amount of specific RNase H cleavage at the 3' terminus of the polypurine tract, which is required for primer removal, An alanine substitution at position 232 led to loss of cleavage specificity, although total activity was close to the wild-type level, Taken together, these results demonstrate for the first time that there are residues in human immunodeficiency virus type 1 reverse transcriptase which are specifically involved in protein-nucleic acid interactions with RNA primers. C1 NICHHD,MOL GENET LAB,NIH,BETHESDA,MD 20892. CASE WESTERN RESERVE UNIV,SCH MED,DIV INFECT DIS,CLEVELAND,OH 44106. FU NIGMS NIH HHS [GM 52263] NR 49 TC 58 Z9 58 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 16 PY 1997 VL 272 IS 20 BP 13262 EP 13269 DI 10.1074/jbc.272.20.13262 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WZ384 UT WOS:A1997WZ38400058 PM 9148945 ER PT J AU Rolfes, RJ Zhang, F Hinnebusch, AG AF Rolfes, RJ Zhang, F Hinnebusch, AG TI The transcriptional activators BAS1, BAS2, and ABF1 bind positive regulatory sites as the critical elements for adenine regulation of ADE5,7 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; DNA-BINDING; HIS4 TRANSCRIPTION; ESCHERICHIA-COLI; HO PROMOTER; ADE2 GENE; YEAST; PROTEIN; SEQUENCE; TRANSFORMATION AB Adenine repression of the purine nucleotide biosyn thetic genes in Saccharomyces cerevisiae involves downregulation of the activator protein BAS1 or BASS by an unknown mechanism, To determine the minimal cis-acting requirements for adenine regulation, hybrid promoter constructs were made between ADE5,7 promoter fragments and a CYC1-lacZ reporter, A 139-nucleotide fragment containing two BAS1 binding sites was sufficient to confer adenine regulation on the CYC1-lacZ reporter, Analysis of deletion and substitution mutations led to the conclusion that the proximal BAS1 binding site is both necessary and sufficient for regulation, whereas the distal site augments the function of the proximal site, By performing saturation mutagenesis, we found two essential regions that flank the proximal site, An ABF1 consensus sequence is within one of these regions, and mutations that impaired in vitro ABF1 binding impaired promoter activity in vivo. A second region is AT-rich and appears to bind BASS, No substitution mutations led to high level constitutive promoter activity as would be expected from removal of an upstream repression sequence. Our results indicate that ABF1, BAS1, and BASS are required for ADE5,7 pro meter function and that adenine repression most likely involves activator modification or a negative regulator that does not itself bind DNA. C1 NICHHD, LAB EUKARYOT GENE REGULAT, NIH, BETHESDA, MD 20892 USA. RP GEORGETOWN UNIV, DEPT BIOL, WASHINGTON, DC 20057 USA. NR 36 TC 31 Z9 33 U1 2 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 16 PY 1997 VL 272 IS 20 BP 13343 EP 13354 DI 10.1074/jbc.272.20.13343 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WZ384 UT WOS:A1997WZ38400070 PM 9148957 ER PT J AU Biswas, I Hsieh, P AF Biswas, I Hsieh, P TI Interaction of MutS protein with the major and minor grooves of a heteroduplex DNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CONTAINING DEOXYTRIDECANUCLEOTIDE DUPLEXES; NUCLEAR-MAGNETIC-RESONANCE; COLI RNA-POLYMERASE; ESCHERICHIA-COLI; MISMATCH-REPAIR; FLANKING SEQUENCE; DEOXYOLIGONUCLEOTIDE DUPLEX; CONFORMATIONAL TRANSITIONS; ENCODED PROTEIN; BASE-PAIRS AB Thermus aquaticus MutS protein is a DNA mismatch repair protein that recognizes and binds to heteroduplex DNAs containing mispaired or unpaired bases. Using enzymatic and chemical probe methods, we have examined the binding of Tag MutS protein to a heteroduplex DNA having a single unpaired thymidine residue. DNase I footprinting identifies a symmetrical region of protection 24-28 nucleotides long centered on the unpaired base. Methylation protection and interference studies establish that Tag MutS protein makes contacts with the major groove of the heteroduplex in the immediate vicinity of the unpaired base. Hydroxyl radical and 1,10-phenanthroline-copper footprinting experiments indicate that MutS also interacts with the minor groove near the unpaired base. Together with the identification of key phosphate groups detected by ethylation interference, these data reveal critical contact points residing in the major and minor grooves of the heteroduplex DNA. C1 NIDDK,GENET & BIOCHEM BRANCH,NIH,BETHESDA,MD 20892. NR 49 TC 36 Z9 36 U1 2 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 16 PY 1997 VL 272 IS 20 BP 13355 EP 13364 DI 10.1074/jbc.272.20.13355 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WZ384 UT WOS:A1997WZ38400071 PM 9148958 ER PT J AU Zhang, C Baumgartner, RA Yamada, K Beaven, MA AF Zhang, C Baumgartner, RA Yamada, K Beaven, MA TI Mitogen-activated protein (MAP) kinase regulates production of tumor necrosis factor-alpha and release of arachidonic acid in mast cells - Indications of communication between p38 and p42 MAP kinases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYTOSOLIC PHOSPHOLIPASE A(2); BASOPHILIC LEUKEMIA-CELLS; CYTOKINE BIOSYNTHESIS; RBL-2H3 CELLS; IGE-RECEPTOR; INHIBITORS; PATHWAY; LINE; RECONSTITUTION; RAF-1 AB Aggregation of the high affinity IgE receptor (Fc epsilon RI) in a mast cell line resulted in activation of the p42 and the stress-activated p38 mitogen-activated protein (MAP) kinases. Selective inhibition of these respective kinases with PD 098059 and SE 203580 indicated that p42 MAP kinase, but not p38 MAP kinase, contributed to the production of the cytokine, tumor necrosis factor a, and the release of arachidonic acid in these cells. Neither kinase, however, was essential for Fc epsilon RI-mediated degranulation or constitutive production of tumor growth factor-beta. Studies with SE 203580 and the p38 MAP kinase activator anisomycin also revealed that p38 MAP kinase negatively regulated activation of p42 MAP kinase and the responses mediated by this kinase. C1 NHLBI,LAB MOL IMMUNOL,NIH,BETHESDA,MD 20892. NR 41 TC 174 Z9 177 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 16 PY 1997 VL 272 IS 20 BP 13397 EP 13402 DI 10.1074/jbc.272.20.13397 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WZ384 UT WOS:A1997WZ38400076 PM 9148963 ER PT J AU Sagawa, K Swaim, W Zhang, J Unsworth, E Siraganian, RP AF Sagawa, K Swaim, W Zhang, J Unsworth, E Siraganian, RP TI Aggregation of the high affinity IgE receptor results in the tyrosine phosphorylation of the surface adhesion protein PECAM-1 (CD31) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; CYTOPLASMIC DOMAIN; SIGNAL-TRANSDUCTION; MONOCLONAL-ANTIBODIES; MAST-CELLS; IN-VIVO; MOLECULE-1 PECAM-1; HISTAMINE-RELEASE; KINASE P72(SYK); BINDING AB One of the earliest events after aggregation of the high affinity receptor for IgE (Fc epsilon RI) on mast cells is the activation of protein tyrosine kinases resulting in tyrosine phosphorylation of numerous proteins, Using a monoclonal antibody raised against the rat basophilic leukemia RBL-2H3 cells, we identified that platelet/endothelial cell adhesion molecule 1 (PECAM-1 or CD31) was tyrosine phosphorylated in these cells, Aggregation of PECAM-1 did not induce a detectable increase in its tyrosine phosphorylation, nor did it result in degranulation, However, the minimal tyrosine phosphorylation of PECAM-1 in nonstimulated cells was dramatically increased after Fc epsilon RI aggregation, This receptor-induced tyrosine phosphorylation of PECAM-1 was an early event, independent of Ca2+ influx or of the activation of protein kinase C and of cell adhesion, PECAM-1 is an adhesion molecule that is required for the transmigration of leukocytes across the endothelium into sites of inflammation, Therefore tyrosine phosphorylation of PECAM-1 may modulate its interaction with other molecules, thereby regulating the migration of basophils into inflammatory sites. C1 NIDR,IMMUNOL LAB,NIH,BETHESDA,MD 20892. US FDA,FACIL BIOTECHNOL RESOURCES,BETHESDA,MD 20892. NR 53 TC 43 Z9 43 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 16 PY 1997 VL 272 IS 20 BP 13412 EP 13418 DI 10.1074/jbc.272.20.13412 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WZ384 UT WOS:A1997WZ38400078 PM 9148965 ER PT J AU Wang, X Brownstein, MJ Young, WS AF Wang, X Brownstein, MJ Young, WS TI PG25, a pineal-specific cDNA, cloned by differential display PCR (DDPCR) and rapid amplification of cDNA ends (RACE) SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE pineal gland; cDNA RACE; differential display PCR; in situ hybridization ID MESSENGER-RNAS; CLONING; GENES AB Synthesis of melatonin in the mammalian pineal gland is regulated by the rhythmic expression of acetyl-CoA: serotonin N-acetyltransferase (SNAT) and other unknown factors. To screen for pineal specific mRNAs potentially involved in melatonin synthesis and/or regulation, differential display PCR (DDPCR) was employed. We used 80 primer pairs and examined 40 bands of interest. One of the pineal specific clones (relative to brain and eye), PG25, was studied further. Hybridization histochemical and Northern analyses confirmed its tissue specificity. The size of the corresponding mRNA is 2.4 kb. A cDNA (2 kb) containing the coding region was obtained using a long-template PCR-based RACE technique. A data base search indicates that PG25 is highly homologous to a recently identified human lung endothelial cell-specific gene, ESM-1. Interestingly, not only the amino acid sequences but also the cDNA sequences, including the long 3' untranslated regions, are highly similar. This suggests that the conserved 3' untranslated region may carry information to regulate its own expression. Northern analysis revealed that PG25 is also expressed in the rat lung, but at a much lower (10%) level compared to the pineal. Finally, our work shows the feasibility of a fast, integrated PCR-based cloning method for obtaining long, potentially full-length cDNAs with restricted expression in anatomically complex regions of the brain. This protocol combining several existing methodologies is suitable for use with limited tissue sources and uses minimal amounts of isotopes. (C) 1997 Elsevier Science B.V. C1 NIMH,LAB CELLULAR & MOL REGULAT,BETHESDA,MD 20892. NIMH,GENET SECT,BETHESDA,MD 20892. RI Young, W Scott/A-9333-2009; Brownstein, Michael/B-8609-2009 OI Young, W Scott/0000-0001-6614-5112; NR 9 TC 8 Z9 12 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD MAY 16 PY 1997 VL 73 IS 2 BP 187 EP 191 DI 10.1016/S0165-0270(97)02237-1 PG 5 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA XC661 UT WOS:A1997XC66100010 PM 9196290 ER PT J AU Ge, P Kirk, KL AF Ge, P Kirk, KL TI Synthesis of 2-deoxy-2-halo-L-ascorbic acids SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID FLUORINATION AB 2-Iodo- and 2-bromo-2-deoxy-L-ascorbic acids (2 and 3) were prepared by facile halogenation of 2-deoxy-L-ascorbic acid (6) with NIS and NBS, respectively. Likewise, chlorination with NCS produced 2-chloro-2-deoxy-L-ascorbic acid (4), but formation of 4 was accompanied by formation of the dichloro hemiketal 9. Direct fluorination of 6 with 1-chloro-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (F-TEDA-BF4) gave only the difluoro hemiketal. 10. A convenient synthesis of 2-deoxy-2-fluoro-L-ascorbic acid (5) was achieved by an indirect route. Fluorination of 2-bromo-2-deoxy-L-ascorbic acid (3) with F-TEDA-BF4 produced the bromofluoro hemiketal 16 as a mixture of diastereoisomers. Debromination with tributyltin hydride gave 5 in good yield. C1 NIDDKD,BIOORGAN CHEM LAB,NIH,BETHESDA,MD 20892. NR 11 TC 24 Z9 24 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD MAY 16 PY 1997 VL 62 IS 10 BP 3340 EP 3343 DI 10.1021/jo962394b PG 4 WC Chemistry, Organic SC Chemistry GA WZ555 UT WOS:A1997WZ55500048 ER PT J AU Dunston, GM Akinsete, O Collins, FS AF Dunston, GM Akinsete, O Collins, FS TI Diabetes project SO SCIENCE LA English DT Letter C1 NATL HUMAN GENOME RES INST,BETHESDA,MD 20892. RP Dunston, GM (reprint author), HOWARD UNIV,AFRICA AMER DIABET MELLITUS PROJECT,WASHINGTON,DC 20059, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAY 16 PY 1997 VL 276 IS 5315 BP 1013 EP 1013 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WZ225 UT WOS:A1997WZ22500003 PM 9173530 ER PT J AU Pietinen, P Ascherio, A Korhonen, P Hartman, AM Willett, WC Albanes, D Virtamo, J AF Pietinen, P Ascherio, A Korhonen, P Hartman, AM Willett, WC Albanes, D Virtamo, J TI Intake of fatty acids and risk of coronary heart disease in a cohort of Finnish men - The alpha-tocopherol, beta-carotene cancer prevention study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cardiovascular diseases; diet; fats; lipids; mortality ID MYOCARDIAL-INFARCTION; FISH CONSUMPTION; ADIPOSE-TISSUE; 20-YEAR MORTALITY; SERUM-CHOLESTEROL; 10-YEAR MORTALITY; DIETARY-INTAKE; HIGH-DENSITY; DEATH; WOMEN AB The relation of intakes of specific fatty acids and the risk of coronary heart disease was examined in a cohort of 21,930 smoking men aged 50-69 years who were initially free of diagnosed cardiovascular disease. All men participated in the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study and completed a detailed and validated dietary questionnaire at baseline, After 6.1 years of follow-up from 1985-1988, the authors documented 1,399 major coronary events and 635 coronary deaths, After controlling for age, supplement group, several coronary risk factors, total energy, and fiber intake, the authors observed a significant positive association between the intake of frans-fatty acids and the risk of coronary death, For men in the top quintile of frans-fatty acid intake (median=6.2 g/day), the multivariate relative risk of coronary death was 1.39 (95% confidence interval (CI) 1.09-1.78) (p for trend=0.004) as compared with men in the lowest quintile of intake (median=1.3 g/day). The intake of omega-3 fatty acids from fish was also directly related to the risk of coronary death in the multivariate model adjusting also for frans-saturated and cis-monounsaturated fatty acids (relative risk (RR)=1.30, 95% CI 1.01-1.67) (p for trend=0.06 for men in the highest quintile of intake compared with the lowest), There was no association between intakes of saturated or cis-monounsaturated fatty acids, linoleic or linolenic acid, or dietary cholesterol and the risk of coronary deaths. All the associations were similar but somewhat weaker for all major coronary events. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,BOSTON,MA 02115. NATL CANC INST,DIV CANC PREVENT & CONTROL,BETHESDA,MD. RP Pietinen, P (reprint author), NATL PUBL HLTH INST,DEPT NUTR,MANNERHEIMINTIE 166,FIN-00300 HELSINKI,FINLAND. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01-CN-45165] NR 51 TC 316 Z9 332 U1 0 U2 13 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAY 15 PY 1997 VL 145 IS 10 BP 876 EP 887 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WY376 UT WOS:A1997WY37600002 PM 9149659 ER PT J AU Gabriel, CM Minor, JR Vogel, S Piscitelli, SC AF Gabriel, CM Minor, JR Vogel, S Piscitelli, SC TI Supportive care during aldesleukin therapy for patients infected with human immunodeficiency virus SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article ID INTERLEUKIN-2 C1 NIH,DEPT PHARM,WARREN G MAGNUSON CLIN CTR,CLIN PHARMACOKINET RES LAB,BETHESDA,MD 20892. NIAID,DEPT PHARM,WARREN G MAGNUSON CLIN CTR,NIH,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. NR 5 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD MAY 15 PY 1997 VL 54 IS 10 BP 1191 EP 1193 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WZ624 UT WOS:A1997WZ62400013 PM 9161628 ER PT J AU Corti, MC Guralnik, JM Salive, ME Harris, T Ferrucci, L Glynn, RJ Havlik, RJ AF Corti, MC Guralnik, JM Salive, ME Harris, T Ferrucci, L Glynn, RJ Havlik, RJ TI Clarifying the direct relation between total cholesterol levels and death from coronary heart disease in older persons SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CARDIOVASCULAR HEALTH; FOLLOW-UP; MORTALITY; RISK; PEOPLE; HYPERCHOLESTEROLEMIA; HYPOCHOLESTEROLEMIA; ASSOCIATION; MODELS; ADULTS AB Background: The importance of total cholesterol level as a risk factor for coronary heart disease in older adults is controversial. Objective: To determine whether findings showing that total cholesterol level is not an important risk factor for coronary heart disease in older adults are the result of inadequate adjustment for co-occurring diseases and frailty. Design: Multicenter, longitudinal study with 5-year follow-up for death. Participants: 4066 men and women from East Boston, Massachusetts; Iowa and Washington counties, Iowa; and New Haven, Connecticut. Measurements: In 1988, participants were interviewed about their health status and had blood samples taken. Mortality follow-up was through 1992. Results: In analyses that included all fatal coronary heart disease events (252 deaths) and did not adjust for risk factors for coronary heart disease and measures of frailty, persons with the lowest total cholesterol levels (less than or equal to 4.15 mmol/L [less than or equal to 160 mg/dL]) had the highest rate of death from coronary heart disease, whereas those with elevated total cholesterol levels (greater than or equal to 6.20 mmol/L [greater than or equal to 240 mg/dL]) seemed to have a lower risk for death from coronary heart disease (P for trend = 0.04). After adjustment for established risk factors for coronary heart disease and markers of poor health (including chronic conditions, low serum iron and albumin levels) and exclusion of 44 deaths from coronary heart disease that occurred within the first year, elevated total cholesterol levels predicted increased risk for death from coronary heart disease, and the risk for death from coronary heart disease decreased as cholesterol levels decreased (P for trend = 0.005). Conclusions: Elevated total cholesterol level is a risk factor for death from coronary heart disease in older adults, and the apparent adverse effects associated with low cholesterol levels are secondary to comorbidity and frailty. This suggests that excluding older persons from cholesterol screening is inappropriate, but interpretation of screening results in older persons requires clinical judgment. Results from controlled clinical trials are needed to clarify this issue. C1 US FDA, EPIDEMIOL BRANCH, CTR BIOL EVALUAT & RES, ROCKVILLE, MD 20852 USA. BRIGHAM & WOMENS HOSP, DEPT MED, DIV PREVENT MED, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. NATL INST RES & CARE ELDERLY, FIESOLE, ITALY. RP NIA, EPIDEMIOL DEMOG & BIOMETRY PROGRAM,NIH, 7201 WISCONSIN AVE,GATEWAY BLDG, ROOM 3C-309, BETHESDA, MD 20892 USA. FU NIA NIH HHS [N01-AG-02105, N01-AG-02106, N01-AG-02107] NR 38 TC 152 Z9 154 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 15 PY 1997 VL 126 IS 10 BP 753 EP + PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA WZ823 UT WOS:A1997WZ82300003 PM 9148647 ER PT J AU Gueyffier, F Boutitie, F Boissel, JP Pocock, S Coope, J Cutler, J Ekbom, T Fagard, R Friedman, L Perry, M Prineas, R Schron, E AF Gueyffier, F Boutitie, F Boissel, JP Pocock, S Coope, J Cutler, J Ekbom, T Fagard, R Friedman, L Perry, M Prineas, R Schron, E TI Effect of antihypertensive drug treatment on cardiovascular outcomes in women and men - A meta-analysis of individual patient data from randomized, controlled trials SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE antihypertensive agents; sex factors; cardiovascular diseases; outcome and process assessment (health care); hypertension ID BLOOD-PRESSURE; HYPERTENSION; MORBIDITY; MORTALITY; DISEASE; INFARCTION; STROKE; HEALTH AB Background: Trials of drug therapy for hypertension have shown that such therapy has a clear overall benefit in preventing cardiovascular disease. Although these trials have included slightly more women than men, it is still not clear whether treatment benefit is similar for both sexes. Objective: To quantify the average treatment effect in both sexes and to determine whether available data show significant differences in treatment effect between women and men. Design: Subgroup meta-analysis of individual patient data according to sex. Analysis was based on seven trials from the INDANA (INdividual Data ANalysis of Antihypertensive intervention trials) database and was adjusted for possible confounders. Patients: 20 802 women and 19 975 men recruited between 1972 and 1990. Interventions: Primarily beta-blockers and thiazide diuretics. Results: In women, treatment effect was statistically significant for stroke (fatal strokes and all strokes) and for major cardiovascular events. In men, it was statistically significant for all categories of events (total and specific mortality, all coronary events, all strokes, and major cardiovascular events). The odds ratios for any category of event did not differ significantly between men and women. In absolute terms, the benefit in women was seen primarily for strokes; in men, treatment prevented as many coronary events as strokes. Graphical analyses suggest that these results Could be completely explained by the difference in untreated risk. Conclusions: In terms of relative risk, treatment benefit did not differ between women and men. The absolute risk reduction attributable to treatment seemed to depend on untreated risk. These findings underline the need to predict accurately the untreated cardiovascular risk of an individual person in order to rationalize and individualize antihypertensive treatment. C1 UNIV LONDON LONDON SCH HYG & TROP MED,DEPT EPIDEMIOL & POPULAT SCI,MED STAT UNIT,LONDON WC1E 7HT,ENGLAND. BOLLINGTON MED CTR,MACCLESFIELD SK10 5JL,CHESHIRE,ENGLAND. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,ROCKLEDGE CTR 2,BETHESDA,MD 20892. UZ PELLENBERG,B-3212 PELLENBERG,BELGIUM. WASHINGTON UNIV,ST LOUIS,MO 63110. UNIV MIAMI,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,MIAMI,FL 33136. LUND UNIV,DALBY,SWEDEN. RP Gueyffier, F (reprint author), UNIV LYON 1,SERV PHARMACOL CLIN,162 AVE LACASSAGNE,BP 3041,F-69394 LYON 03,FRANCE. RI Gueyffier, Francois/B-8545-2008 OI Gueyffier, Francois/0000-0002-9921-0977 NR 31 TC 223 Z9 229 U1 1 U2 6 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 15 PY 1997 VL 126 IS 10 BP 761 EP & PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA WZ823 UT WOS:A1997WZ82300004 PM 9148648 ER PT J AU Liu, SY Stadtman, TC AF Liu, SY Stadtman, TC TI Selenophosphate synthetase: Enzyme labeling studies with [gamma-P-32]ATP, [beta-P-32]ATP, [8-C-14]ATP, and [Se-75]selenide SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE selenophosphate; [P-32]ATP; P-32-labeled enzyme ID SELD GENE-PRODUCT; ESCHERICHIA-COLI AB Selenophosphate synthetase catalyzes a reaction in which ATP and selenide are converted to H3SePO3, H3PO4, and AMP in a 1:1:1 ratio. Selenophosphate is derived from the gamma phosphoryl group and orthophosphate from the beta phosphoryl group of ATP. In the absence of selenide, a slow reaction in which ATP is converted quantitatively to 2 H3PO4 and AMP occurs. Labeling experiments carried out to detect a putative enzyme-bound pyrophosphate intermediate in the overall reaction showed that up to 0.6 equivalent of the P-32 label from [gamma-P-32]ATP was bound to protein wider enzyme turnover conditions, but only a negligible amount of P-32 from [beta-P-32]ATP was present. Thus, no Enz-PP intermediate was present in a detectable amount under the experimental conditions used. Isolated enzyme samples contained Se-75 from Se-75-labeled selenide and [C-14]AMP from [8-C-14]ATP in amounts similar to the bound P-32 from [gamma-P-32]ATP, suggesting that two of the final products, selenophosphate and AMP, were the radioactive compounds detected in these experiments. (C) 1997 Academic Press. C1 NHLBI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. NR 10 TC 10 Z9 10 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 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAY 15 PY 1997 VL 341 IS 2 BP 353 EP 359 DI 10.1006/abbi.1997.9990 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WZ643 UT WOS:A1997WZ64300022 PM 9169026 ER PT J AU Pegg, AE Chung, L Moschel, RC AF Pegg, AE Chung, L Moschel, RC TI Effect of DNA on the inactivation of O-6-alkylguanine-DNA alkyltransferase by 9-substituted O-6-benzylguanine derivatives SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE O-6-alkylguanine-DNA alkyltransferase; O-6-benzylguanine; chloroethylating agents; methylating agents; chemotherapy ID ALKYLATING-AGENTS; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; TUMOR-CELLS; REPAIR; METHYLTRANSFERASE; O6-BENZYLGUANINE; DEPLETION; PROTEIN AB Studies were carried out on the inactivation of pure human O-6-alkylguanine-DNA alkyltransferase by 9-substituted O-6-benzylguanine derivatives in the presence and absence of DNA. The addition of DNA increased the rate of inactivation of the alkyltransferase by O-6-benzylguanine and its 9-methyl derivative but had little effect on the rate of inactivation by the 9 cyanomethyl derivative. In contrast, when O-6-benzylguanine derivatives with larger 9-substituents such as ribose, 2'-deoxyribose, dihydrotestosterone, or 2-hydroxy-3-(isopropoxy)propyl were used, the addition of DNA was strongly inhibitory to the inactivation. In the case of O-6-benzylguanine, O-6-benzylguanosine, and O-6-benzyl-2'-deoxyguanosine, these results were confirmed by directly measuring the rate of formation by the alkyltransferase of guanine, guanosine, or 2'-deoxyguanosine, respectively. The data indicated that the presence of DNA activated the alkyltransferase, rendering it more reactive with O-6-benzylguanine or O-6-benzyl 9-methylguanine, but that DNA interferes with the binding of inhibitors with larger 9-substituents, presumably by competing for the same binding site. Since these inactivators readily inactivate alkyltransferase in cells, the amount of cellular alkyltransferase bound to DNA must be small or readily exchangeable with the free form. (C) 1997 Elsevier Science Inc. C1 PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT PHARMACOL,HERSHEY,PA 17033. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHEM CARCINOGENESIS LAB,FREDERICK,MD 21702. RP Pegg, AE (reprint author), PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT CELLULAR & MOL PHYSIOL,POB 850,HERSHEY,PA 17033, USA. FU NCI NIH HHS [CA-57725, CA-71976] NR 18 TC 17 Z9 18 U1 0 U2 3 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 MAY 15 PY 1997 VL 53 IS 10 BP 1559 EP 1564 DI 10.1016/S0006-2952(97)00060-9 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XP115 UT WOS:A1997XP11500021 PM 9260884 ER PT J AU Kulynych, JJ Luevano, LF Jones, DW Weinberger, DR AF Kulynych, JJ Luevano, LF Jones, DW Weinberger, DR TI Cortical abnormality in schizophrenia: An in vivo application of the Gyrification Index SO BIOLOGICAL PSYCHIATRY LA English DT Article DE gyrification; cortex; magnetic resonance imaging; schizophrenia ID TEMPORAL-LOBE; BRAIN ABNORMALITIES; CEREBRAL-CORTEX; VOLUME; DISORDER; PATTERN AB To investigate the hypothesis that patients with schizophrenia exhibit gross cortical abnormalities of developmental origin, we utilized the gyrification index (GI) (ratio of inner to outer cortical contours), a measure of overall cortical folding, in an in vivo magnetic resonance imaging study of young, strongly right-handed male patients and controls. The two groups did not differ with respect to whole-brain volume, age, or handedness, In an examination confined to the left hemisphere, mean GI values were significantly reduced in the patient group in both anterior and posterior regions. Neither age nor length of illness were found to be significant predictors of GI variance in the patient group, suggesting that GI reductions do not result from an ongoing atrophic process. Rather, these results are consistent with the hypothesis of neurodevelopmental abnormalities in schizophrenia that result in an overall reduction in cortical folding. (C) 1997 Society of Biological Psychiatry. C1 NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,INTRAMURAL RES PROGRAM,WASHINGTON,DC 20032. STANFORD UNIV,SCH LAW,STANFORD,CA 94305. NR 31 TC 81 Z9 81 U1 2 U2 6 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 MAY 15 PY 1997 VL 41 IS 10 BP 995 EP 999 DI 10.1016/S0006-3223(96)00292-2 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WV921 UT WOS:A1997WV92100002 PM 9129779 ER PT J AU Mackall, CL Fleisher, TA Brown, MR Andrich, MP Chen, CC Feuerstein, IM Magrath, IT Wexler, LH Dimitrov, DS Gress, RE AF Mackall, CL Fleisher, TA Brown, MR Andrich, MP Chen, CC Feuerstein, IM Magrath, IT Wexler, LH Dimitrov, DS Gress, RE TI Distinctions between CD8(+) and CD4(+) T-cell regenerative pathways result in prolonged T-cell subset imbalance after intensive chemotherapy SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; VERSUS-HOST DISEASE; COSTIMULATORY MOLECULE; IMMUNE RECONSTITUTION; LYMPHOCYTES; POPULATIONS; EXPRESSION; INFECTION; CD28; MATURATION AB Rapid recovery of CD4(+) T cells after intensive chemotherapy is limited by an age-dependent decline in thymopoiesis, Here we sought to determine whether similar limitations exist for CD8(+) T-cell regeneration. After intensive chemotherapy, CD8(+) T cells had a faster effective doubling time than CD4(+) T cells (median, 12.6 v 28.2 days, P < .05), Accordingly, at 3 months posttherapy, mean CD8(+) T-cell-number had returned to baseline, whereas mean CD4(+) T-cell number was only 35% of pretherapy values (P < .05), These differences were primarily due to very rapid expansion of CD8(+)CD57(+) and CD8(+)CD28(-) subsets. At 3 months posttherapy, there was no relationship between age and CD8(+) T-cell number (R = .02), whereas CD4(+) T cell number was inversely related to age (R = -.66) and there were no discernible differences in CD8(+) recovery among patients with or without thymic enlargement, whereas CD4(+) recovery was enhanced in patients with thymic enlargement after chemotherapy (P <.01). Therefore thymic-independent pathways of T-cell regeneration appear to rapidly regenerate substantial numbers of CD8(+), but not CD4(+) T cells, resulting in prolonged T-cell subset imbalance after T-cell depletion, These inherent distinctions between CD4(+) v CD8(+) T-cell regeneration may have significant implications for immunotherapeutic strategies undertaken to eradicate minimal residual neoplastic disease after cytoreductive chemotherapy. This is a US government work. There are no restrictions on its use. C1 NATL CANC INST,PEDIAT BRANCH,BETHESDA,MD. NATL CANC INST,EXPT IMMUNOL BRANCH,BETHESDA,MD. NATL CANC INST,MED BRANCH,BETHESDA,MD. NATL CANC INST,MATH BIOL LAB,BETHESDA,MD. NIH,DEPT CLIN PATHOL,CTR CLIN,BETHESDA,MD 20892. NIH,DEPT NUCL MED,CTR CLIN,BETHESDA,MD 20892. NIH,DEPT RADIOL,CTR CLIN,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,HENRY M JACKSON FDN ADVANCEMENT MIL MED,BETHESDA,MD 20814. NR 49 TC 248 Z9 253 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 1997 VL 89 IS 10 BP 3700 EP 3707 PG 8 WC Hematology SC Hematology GA XD976 UT WOS:A1997XD97600023 PM 9160675 ER PT J AU Zhan, ZR Sandor, VA Gamelin, E Regis, J Dickstein, B Wilson, W Fojo, AT Bates, SE AF Zhan, ZR Sandor, VA Gamelin, E Regis, J Dickstein, B Wilson, W Fojo, AT Bates, SE TI Expression of the multidrug resistance-associated protein gene in refractory lymphoma: Quantitation by a validated polymerase chain reaction assay SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; HUMAN TUMOR-CELLS; LUNG-CANCER; DRUG ACCUMULATION; MRP; OVEREXPRESSION; INHIBITION; EFFLUX; LINES; MDR-1 AB Previous work investigating the role of MDR-1 overexpression in relapsed and refractory lymphoma led us to investigate a possible role for multidrug resistance-associated protein (MRP) as a cause of resistance in patients who did not overexpress MDR-1. A quantitative polymerase chain reaction (PCR) method for measuring MRP expression was validated. Immunoblot analysis suggested that no major discrepancy was present between mRNA expression and protein levels. MRP levels were found to be independent of sample tumor content by immunophenotyping, suggesting that the presence of normal cells had no significant impact on measurements of MRP expression. We evaluated MRP in 55 biopsy samples from 40 patients with refractory lymphoma enrolled on a trial of infusional chemotherapy (EPOCH), Pre- and post EPOCH samples were available from 15 patients. MRP levels were also evaluated in 16 newly diagnosed, untreated lymphoma patient samples. No significant difference in MRP mRNA expression was noted between pre- and post-EPOCH groups. Also, MRP levels in the newly diagnosed patient samples were not significantly different from either pre- or post-EPOCH groups. Two of 15 paired pre- and post-EPOCH patient samples exhibited overexpression of MRP after EPOCH chemotherapy, with measured increases of 10-fold and 18-fold. We conclude that MRP overexpression is not responsible for non-P-glycoprotein (Pgp)-mediated drug resistance in the majority of these patients, although it may be important in a subset of patients, Defining this subset prospectively could aid in the development of clinical trials of MRP modulation in drug-resistant lymphoma. This is a US government work. There are no restrictions on its use. C1 NCI,MED BRANCH,NIH,BETHESDA,MD 20892. NR 32 TC 29 Z9 33 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 MAY 15 PY 1997 VL 89 IS 10 BP 3795 EP 3800 PG 6 WC Hematology SC Hematology GA XD976 UT WOS:A1997XD97600034 PM 9160686 ER PT J AU Figg, WD Kroog, G Duray, P Walther, MM Patronas, N Sartor, O Reed, E AF Figg, WD Kroog, G Duray, P Walther, MM Patronas, N Sartor, O Reed, E TI Flutamide withdrawal plus hydrocortisone resulted in clinical complete response in a patient with prostate carcinoma SO CANCER LA English DT Article DE prostate carcinoma; metastatic; hormone refractory; androgen independent ID ANDROGEN-RECEPTOR GENE; ANTIGEN DECLINE; ANTIANDROGEN WITHDRAWAL; CANCER; MUTATION; CASODEX; CELLS AB BACKGROUND. Combined androgen blockade plus (CAB) (medical or surgical castration plus antiandrogen therapy) is considered by many to be the optimal endocrine maneuver for patients with metastatic prostate carcinoma. When progression occurs after CAB, the discontinuation of the antiandrogen is recommended. The authors present a patient that had a clinical complete response to flutamide withdrawal plus hydrocortisone that, at last follow-up, had been maintained for more than 46 months. METHODS. A 71-year-old man with a positive family history of prostate carcinoma presented in 1989 with urinary frequency and a suspicious digital rectal examination. He was found to have a poorly differentiated adenocarcinoma (Gleason 4+4). He was started on CAB and his prostate specific antigen (PSA) concentration declined from 96 ng/mL to the normal range and was maintained for the next 24 months. In 1991 his PSA began to rise, and reached 64 ng/mL by 1993. The patient was enrolled on a clinical trial that discontinued the flutamide administration and hydrocortisone was initiated. RESULTS. Physical examination at the time of enrollment was unremarkable. His PSA declined to below the limits of detection after this maneuver and at last follow-up had been maintained there for more than 46 months. In 1995, the patient underwent a repeat biopsy of the prostate and all six tissue cores were negative for carcinoma. At last follow-up in December 1996, the patient had no evidence of disease and was being followed routinely; however, the authors were continuing treatment with testicular suppression (leuprolide) plus hydrocortisone. CONCLUSIONS. The authors believe the residual androgens and steroids produced by the adrenal cortex play a meaningful role in prostate carcinoma cell proliferation. Based on this case and data from trials supporting the activity of flutamide withdrawal plus adrenal suppression, it appears reasonable to evaluate prospectively the discontinuation of antiandrogen versus antiandrogen withdrawal plus adrenal suppression in individuals failing CAB. (C) 1997 American Cancer Society. C1 NCI,CLIN PHARMACOL BRANCH,DIV CLIN SCI,BETHESDA,MD 20892. NCI,PATHOL LAB,DIV CLIN SCI,BETHESDA,MD 20892. RI Figg Sr, William/M-2411-2016 NR 26 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD MAY 15 PY 1997 VL 79 IS 10 BP 1964 EP 1968 DI 10.1002/(SICI)1097-0142(19970515)79:10<1964::AID-CNCR18>3.0.CO;2-T PG 5 WC Oncology SC Oncology GA WW925 UT WOS:A1997WW92500018 PM 9149024 ER PT J AU EmmertBuck, MR Lubensky, IA Dong, QH Manickam, P Guru, SC Kester, MB Olufemi, SE Agarwal, S Burns, AL Spiegel, AM Collins, FS Marx, SJ Zhuang, ZP Liotta, LA Chandrasekharappa, SC Debelenko, LV AF EmmertBuck, MR Lubensky, IA Dong, QH Manickam, P Guru, SC Kester, MB Olufemi, SE Agarwal, S Burns, AL Spiegel, AM Collins, FS Marx, SJ Zhuang, ZP Liotta, LA Chandrasekharappa, SC Debelenko, LV TI Localization of the multiple endocrine neoplasia type I (MEN1) gene based on tumor loss of heterozygosity analysis SO CANCER RESEARCH LA English DT Article ID PARATHYROID TUMORS; LINKAGE ANALYSIS; SUPPRESSOR GENE; ALLELIC LOSS; CHROMOSOME-11; MARKERS; REGION; CANCER; 11Q13 AB Multiple endocrine neoplasia type I (MEN1) is an inherited syndrome that results in parathyroid, anterior pituitary, and pancreatic and duodenal endocrine tumors as well as foregut carcinoids in affected patients, The gene responsible for the disease has been linked to chromosome 11q13, We analyzed loss of heterozygosity (LOH) in 188 tumors from 81 patients in an attempt to further define the location of the MEN1 gene, Both tumors from MEN1 patients and corresponding sporadic tumors were analyzed, Tumor types included parathyroid, gastrinoma, pancreatic endocrine, pituitary, and lung carcinoid, Six tumors (three MEN1 and three sporadic tumors) were identified that provided important LOH boundaries, Four tumors (two parathyroid tumors, one gastrinoma, and one lung carcinoid tumor) showed allelic loss that placed the MEN1 gene distal to marker PYGM. Two tumors (one gastrinoma and one parathyroid tumor) showed an LOH boundary that placed the gene proximal to D11S449, one of which further moved the telomeric boundary to D11S4936, Taken together, the present data suggest that the MEN1 gene lies between PYGM and D11S4936, a region of approximately 300 kb on chromosome 11q13. C1 NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. NATL HUMAN GENOME RES INST,BETHESDA,MD 20892. RP EmmertBuck, MR (reprint author), NCI,PATHOL LAB,BLDG 10,RM 2A33,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 26 TC 65 Z9 66 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 1997 VL 57 IS 10 BP 1855 EP 1858 PG 4 WC Oncology SC Oncology GA WZ216 UT WOS:A1997WZ21600008 PM 9157974 ER PT J AU Kobayashi, H Yoo, TM Drumm, D Kim, MK Sun, BF Le, N Webber, KO Pastan, I Waldmann, TA Paik, CH Carrasquillo, JA AF Kobayashi, H Yoo, TM Drumm, D Kim, MK Sun, BF Le, N Webber, KO Pastan, I Waldmann, TA Paik, CH Carrasquillo, JA TI Improved biodistribution of I-125-labeled anti-Tac disulfide-stabilized Fv fragment by blocking its binding to the alpha subunit of the interleukin 2 receptor in the circulation with preinjected humanized anti-Tac IgG SO CANCER RESEARCH LA English DT Article ID SINGLE-CHAIN-FV; RADIOLABELED MONOCLONAL-ANTIBODY; NUDE-MICE BEARING; HAIRY-CELL LEUKEMIA; HUMAN T-CELLS; COLORECTAL-CARCINOMA; IMMUNOGLOBULIN FORMS; F(AB')2 FRAGMENTS; TUMOR XENOGRAFTS; COLON CANCER AB Animal studies using radiolabeled anti-Tac disulfide-stabilized Fv (dsFv) monoclonal antibody have shown formation of complexes in serum with the soluble alpha subunit of the interleukin 2 receptor alpha (sIL-2R alpha). In this study, we improved the targeting of I-125-labeled anti-Tac dsFv to receptor-positive tumors in the presence of circulating receptor by preinjecting unlabeled humanized anti-Tac IgG antibody (HuTac IgG), We used mice bearing SP2/Tac tumor xenografts that express the IL-2R alpha. A positive correlation was seen between tumor size and the concentration of circulating receptor, Tumor-bearing mice were injected with I-125-labeled anti-Tac dsFv (400 ng), either alone or 15 min after injection of HuTac IgG, The I-125-labeled anti-Tac dsFv formed high molecular weight complexes with the sIL-2 alpha. The fraction of the dsFv present in the complexes increased as tumor size increased (greater sIL-2R alpha levels), The fractions of dsFv in the complexes were 9.9- to 11.6-fold higher when sIL-2R alpha was not blocked with preinjected HuTac IgG. The administration of a 12-fold molar excess of HuTac IgG over sIL-2R alpha resulted in >80% of the I-125 activity present as the dsFv rather than in the complexes, Furthermore, the biodistribution of I-125-labeled anti-Tac dsFv was improved by blocking its binding to sIL-2R alpha by preinjecting HuTac IgG, Specifically, in the preinjected group, at 15 min postinjection, the I-125-labeled anti-Tac dsFv levels in tumor increased to 10.8% compared to 5.6% injected dose per gram in the non-preinjected group, In summary, our studies showed that preinjection of HuTac IgG can block the formation of complexes of circulating sIL-2R alpha and I-125-labeled anti-Tee dsFv, This blockade is associated with faster blood clearance, higher tumor uptake, and greater tumor:nontumor ratios of the radiolabeled antibody fragment. C1 NCI, DEPT NUCL MED, NIH, BETHESDA, MD 20892 USA. NCI, WARREN G MAGNUSON CLIN CTR, NIH, BETHESDA, MD 20892 USA. NCI, MOL BIOL LAB, DIV BASIC SCI, NIH, BETHESDA, MD 20892 USA. NCI, METAB BRANCH, DIV CLIN SCI, NIH, BETHESDA, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 61 TC 14 Z9 14 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 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 1997 VL 57 IS 10 BP 1955 EP 1961 PG 7 WC Oncology SC Oncology GA WZ216 UT WOS:A1997WZ21600025 PM 9157991 ER PT J AU Bennett, CB Snipe, JR Resnick, MA AF Bennett, CB Snipe, JR Resnick, MA TI A persistent double-strand break destabilizes human DNA in yeast and can lead to G(2) arrest and lethality SO CANCER RESEARCH LA English DT Article ID SACCHAROMYCES-CEREVISIAE; RECOMBINATION; REPAIR; CHROMOSOME; TRANSFORMATION; REQUIREMENTS; HOMOLOGY; SYSTEM; DAMAGE; CELLS AB Double-strand breaks (DSBs) are an important source of genomic change in many organisms. We have examined the consequences of a persistent versus a rapidly repaired DSB on cell progression, viability, and stability of human DNA contained in dispensable yeast artificial chromosomes (YACs) within the yeast Saccharomyces cerevisiae, An Alu-URA3-YZ integrating plasmid was used to target the YZ sequence to repetitive Alu sequences within the human YAC. The YZ site can be cut by an inducible HO-endonuclease resulting in a DSB, Two classes of DSBs had been identified previously: those that could be rapidly repaired (RR-DSB), through recombination between flanking Alus; and persistent DSBs (C. B. Bennett et al., Mol. Cell. Biol., 16: 4114-4425, 1996). These persistent DSBs (type 1) resulted in G(2) delay and lethality, A third class of DSB is now identified corresponding to a persistent DSB that does not lead to G(2) arrest or lethality (type 2), Unlike YACs in which the DSB was rapidly repaired, the two types of persistent DSBs destabilized the human YAC DNA, resulting in a high likelihood of YAC loss (similar to 85% of surviving colonies), Furthermore, both types of persistent DSBs could be misrepaired, resulting in mostly large internal or terminal deletions in the retained YACs. Therefore, recovery of these altered YACs can occur regardless of the effect of the DSBs on G(2) arrest and cell lethality, If similar events occur in mammalian cells, persistent DSBs could be the initiating events that lead to a loss of heterozygosity and the expression of recessive oncogenes seen in malignant cells. RP Bennett, CB (reprint author), NIEHS,MOL GENET LAB,NIH,RES TRIANGLE PK,NC 27709, USA. NR 34 TC 15 Z9 15 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 1997 VL 57 IS 10 BP 1970 EP 1980 PG 11 WC Oncology SC Oncology GA WZ216 UT WOS:A1997WZ21600027 PM 9157993 ER PT J AU Chen, ZQ Fisher, RJ Riggs, CW Rhim, JS Lautenberger, JA AF Chen, ZQ Fisher, RJ Riggs, CW Rhim, JS Lautenberger, JA TI Inhibition of vascular endothelial growth factor-induced endothelial cell migration by ETS1 antisense oligonucleotides SO CANCER RESEARCH LA English DT Article ID TRANSCRIPTION FACTOR; PROTO-ONCOGENE; T-CELLS; EXPRESSION; ANGIOGENESIS; GENE; DIFFERENTIATION; BINDING; FAMILY; EMBRYOGENESIS AB Vascular endothelial growth factor (VEGF) increased the level of ETS1 mRNA in human umbilical vein endothelial cells (HUVEC) and human lung microvascular endothelial cells (HMVEC-L) over 5-fold. Protein levels were shown to increase concordantly. VEGF was also found to stimulate the invasiveness of endothelial cells as measured by migration through Matrigel- or gelatin-coated membranes. The VEGF-induced invasiveness was inhibited by ETS1 antisense oligonucleotides but not by a sense control. In addition, the ETS1 antisense oligonucleotides reduced the levels of ETS1 and urokinase-type plasminogen activator mRNAs. The antisense oligonucleotides directed against the ETS1 gene thus altered a cellular property of endothelial cells that is correlated with the ability of the cells to migrate through basement membranes. Together, these observations demonstrate a direct role for the ETS1 gene in angiogenesis. C1 NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DATA MANAGEMENT SERV,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,LAB BIOCHEM PHYSIOL,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,LAB GENOM DIVERS,FREDERICK,MD 21702. RI Fisher, Robert/B-1431-2009 NR 37 TC 90 Z9 95 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 1997 VL 57 IS 10 BP 2013 EP 2019 PG 7 WC Oncology SC Oncology GA WZ216 UT WOS:A1997WZ21600033 PM 9157999 ER PT J AU Glick, AB AF Glick, AB TI Transforming growth factor beta 1 suppresses genomic instability independent of a G(1) arrest, p53, and Rb (vol 56, pg 3645, 1996) SO CANCER RESEARCH LA English DT Correction, Addition RP Glick, AB (reprint author), NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892, USA. NR 1 TC 6 Z9 6 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 1997 VL 57 IS 10 BP 2079 EP 2079 PG 1 WC Oncology SC Oncology GA WZ216 UT WOS:A1997WZ21600042 ER PT J AU Bottinger, EP Jakubczak, JL Roberts, ISD Mumy, M Hemmati, P Bagnall, K Merlino, G Wakefield, LM AF Bottinger, EP Jakubczak, JL Roberts, ISD Mumy, M Hemmati, P Bagnall, K Merlino, G Wakefield, LM TI Expression of a dominant-negative mutant TGF-beta type II receptor in transgenic mice reveals essential roles for TGF-beta in regulation of growth and differentiation in the exocrine pancreas SO EMBO JOURNAL LA English DT Article DE in vivo; receptors; signal transduction; transforming growth factor beta; transgenic mice ID TRANSFORMING GROWTH-FACTOR-BETA-1; GENE-EXPRESSION; MESSENGER-RNA; ACINAR-CELLS; FACTOR-BETA-1; INDUCTION; COMPLEX; FIBROBLASTS; APOPTOSIS; CARCINOMA AB Using a dominant-negative mutant receptor (DNR) approach in transgenic mice, we have functionally inactivated transforming growth factor-beta (TGF-beta) signaling in select epithelial cells, The dominant-negative mutant type II TGF-beta receptor blocked signaling by all three TGF-beta isoforms in primary hepatocyte and pancreatic acinar cell cultures generated from transgenic mice, as demonstrated by the loss of growth inhibitory and gene induction responses, However, it had no effect on signaling by activin, the closest TGF-beta family member, DNR transgenic mice showed increased proliferation of pancreatic acinar cells and severely perturbed acinar differentiation. These results indicate that TGF-beta negatively controls growth of acinar cells and is essential for the maintenance of a differentiated acinar phenotype in the exocrine pancreas in vivo. In contrast, such abnormalities were not observed in the liver, Additional abnormalities in the pancreas included fibrosis, neoangiogenesis and mild macrophage infiltration, and these were associated with a marked up-regulation of TGF-beta expression in transgenic acinar cells, This transgenic model of targeted functional inactivation of TGF-beta signaling provides insights into mechanisms whereby loss of TGF-beta responsiveness might promote the carcinogenic process, both through direct effects on cell proliferation, and indirectly through up-regulation of TGF-beta s with associated paracrine effects on stromal compartments. C1 NCI,CHEMOPREVENT LAB,NIH,BETHESDA,MD 20892. NCI,MOL BIOL LAB,NIH,BETHESDA,MD 20892. UNIV MANCHESTER,DEPT PATHOL SCI,MANCHESTER M13 9PT,LANCS,ENGLAND. NR 55 TC 177 Z9 179 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 15 PY 1997 VL 16 IS 10 BP 2621 EP 2633 DI 10.1093/emboj/16.10.2621 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XC307 UT WOS:A1997XC30700008 PM 9184209 ER PT J AU vanGent, DC Hiom, K Paull, TT Gellert, M AF vanGent, DC Hiom, K Paull, TT Gellert, M TI Stimulation of V(D)J cleavage by high mobility group proteins SO EMBO JOURNAL LA English DT Article DE DNA bending; HMG proteins; RAG1 and RAG2; V(D)J recombination ID NONSPECIFIC DNA-BINDING; NUCLEOPROTEIN STRUCTURES; ARCHITECTURAL ELEMENTS; MOUSE THYMOCYTES; HU PROTEIN; RECOMBINATION; COMPLEX; REARRANGEMENT; SITE; HMG1 AB V(D)J recombination requires a pair of signal sequences with spacer lengths of 12 and 23 bp between the conserved heptamer and nonamer elements. The RAG1 and RAG2 proteins initiate the reaction by making double-strand DNA breaks at both signals, and must thus be able to operate on these two different spatial arrangements. We show that the DNA-bending proteins HMG1 and HMG2 stimulate cleavage and RAG protein binding at the 23 bp spacer signal. These findings suggest that DNA bending is important for bridging the longer spacer, and explain how a similar array of RAG proteins could accommodate a signal with either a 12 or a 23 bp spacer. An additional effect of HMG proteins is to stimulate coupled cleavage greatly when both signal sequences are present, suggesting that these proteins also aid the formation of a synaptic complex. C1 NIDDKD,MOL BIOL LAB,NIH,BETHESDA,MD 20892. RI Hiom, Kevin/B-4374-2009 NR 37 TC 186 Z9 190 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 15 PY 1997 VL 16 IS 10 BP 2665 EP 2670 DI 10.1093/emboj/16.10.2665 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XC307 UT WOS:A1997XC30700012 PM 9184213 ER PT J AU Pedone, PV Omichinski, JG Nony, P Trainor, C Gronenborn, AM Clore, GM Felsenfeld, G AF Pedone, PV Omichinski, JG Nony, P Trainor, C Gronenborn, AM Clore, GM Felsenfeld, G TI The N-terminal fingers of chicken GATA-2 and GATA-3 are independent sequence-specific DNA binding domains SO EMBO JOURNAL LA English DT Article DE DNA binding proteins; erythroid gene regulation; GATA proteins; zinc fingers ID TRANSCRIPTION FACTOR GATA-1; ZINC-FINGER; MEGAKARYOCYTIC DIFFERENTIATION; ERYTHROID-DIFFERENTIATION; DEVELOPING HEART; REGULATORY GENE; EXPRESSION; CELLS; MOUSE; PROTEIN AB The GATA family of vertebrate DNA binding regulatory proteins are expressed in diverse tissues and at different times of development. However, the DNA binding regions of these proteins possess considerable homology and recognize a rather similar range of DNA sequence motifs. DNA binding is mediated through two domains, each containing a zinc finger. Previous results have led to the conclusion that although in some cases the N-terminal finger can contribute to specificity and strength of binding, it does not bind independently, whereas the C-terminal finger is both necessary and sufficient for binding, Here we show that although this is true for the N-terminal finger of GATA-1, those of GATA-2 and GATA-3 are capable of strong independent binding with a preference for the motif GATC. Binding requires the presence of two basic regions located on either side of the N-terminal finger. The absence of one of these near the GATA-1 N-terminal finger probably accounts for its inability to bind. The combination of a single finger and two basic regions is a new variant of a motif that has been previously found in the binding domains of other finger proteins. Our results suggest that the DNA binding properties of the N-terminal finger may help distinguish GATA-2 and GATA-3 from GATA-1 and the other GATA family members in their selective regulatory roles in vivo. C1 NIDDK,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NIDDK,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 39 TC 59 Z9 62 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 15 PY 1997 VL 16 IS 10 BP 2874 EP 2882 DI 10.1093/emboj/16.10.2874 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XC307 UT WOS:A1997XC30700030 PM 9184231 ER PT J AU Thomas, BJ Zavitz, KH Dong, XZ Lane, ME Weigmann, K Finley, RL Brent, R Lehner, CF Zipursky, SL AF Thomas, BJ Zavitz, KH Dong, XZ Lane, ME Weigmann, K Finley, RL Brent, R Lehner, CF Zipursky, SL TI roughex down-regulates G(2) cyclins in G(1) SO GENES & DEVELOPMENT LA English DT Article DE cell cycle; cyclin A; eye development; G(I); Drosophila; protein stability ID DEVELOPING DROSOPHILA EYE; CELL-CYCLE; S-PHASE; PATTERN-FORMATION; MAMMALIAN FIBROBLASTS; DNA-REPLICATION; PROTEIN-KINASE; EXPRESSION; TRANSITION; PROGRESSION AB Cell cycle arrest in G(1) at the onset of patterning in the Drosophila eye is mediated by rougher. In rougher mutants, cells accumulate Cyclin A protein in early G(1) and progress into S phase precociously. When Rougher is overexpressed in S/G(2) cells, Cyclin A is mislocalized to the nucleus and degraded, preventing mitosis. Whereas Rougher inhibits Cyclin A accumulation, Cyclin E down-regulates Rougher protein in vivo. Rougher binds to Cyclin E and is a substrate for a Cyclin E-Cdk complex in vitro. These data argue that Rougher inhibits Cyclin A accumulation in early G(1) by targeting Cyclin A for destruction. In late G(1), Rougher is destabilized in a Cyclin E-dependent process, releasing Cyclin A for its role in S/G(2). C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT BIOL CHEM,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,SCH MED,INST MOL BIOL,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,SCH MED,HOWARD HUGHES MED INST,LOS ANGELES,CA 90095. WAYNE STATE UNIV,SCH MED,CTR MOL MED & GENET,DETROIT,MI. MASSACHUSETTS GEN HOSP,DEPT BIOL MOL,BOSTON,MA 02114. UNIV BAYREUTH,DEPT GENET,D-95440 BAYREUTH,GERMANY. RP Thomas, BJ (reprint author), NCI,BIOCHEM LAB,NIH,BETHESDA,MD 20892, USA. FU NIGMS NIH HHS [GM07185] NR 49 TC 59 Z9 59 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 15 PY 1997 VL 11 IS 10 BP 1289 EP 1298 DI 10.1101/gad.11.10.1289 PG 10 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA XB687 UT WOS:A1997XB68700007 PM 9171373 ER PT J AU Nakano, H Shindo, M Yamada, K Yoshida, MC Santee, SM Ware, CF Jenkins, NA Gilbert, DJ Yagita, H Copeland, NG Okumura, K AF Nakano, H Shindo, M Yamada, K Yoshida, MC Santee, SM Ware, CF Jenkins, NA Gilbert, DJ Yagita, H Copeland, NG Okumura, K TI Human TNF receptor-associated factor 5 (TRAF5): CDNA cloning, expression and assignment of the TRAF5 gene to chromosome 1q32 SO GENOMICS LA English DT Article ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; MICE DEFICIENT; MOUSE GENOME; FAMILY; LYMPHOTOXIN; BETA; ACTIVATION; PROTEINS; DOMAIN AB Tumor necrosis factor (TNF) receptor-associated factors (TRAFs) are signal transducers for members of the TNF receptor superfamily. We previously identified murine TRAF5 (mTRAF5) and showed that it specifically interacts with the lymphotoxin-beta receptor (LT-beta R) and activates the transcription factor NF-kappa B. Here we have cloned the human TRAF5 homologue (hTRAF5) by cross hybridization with mTRAF5 cDNA. hTRAF5 cDNA is composed of 2894 nucleotides with a 557-amino-acid open reading frame that exhibits 77.5 and 80% identity to mTRAF5 at the nucleotide and amino acid levels, respectively. Northern blot analysis revealed that hTRAF5 mRNA is expressed in all visceral organs. Western blotting revealed that hTRAF5 protein was abundantly expressed in the human follicular dentritic cell line, FDC1, and to a much lesser degree in several tumor cell lines. Interspecific backcross mapping revealed that Traf5 is located in the distal region of mouse chromosome 1, which shares a region of homology with human chromosome Iq. Fluorescence in situ hybridization confirmed regional localization to human chromosome 1q32. (C) 1997 Academic Press. C1 LA JOLLA INST ALLERGY & IMMUNOL,DIV MOL IMMUNOL,LA JOLLA,CA 92121. HOKKAIDO UNIV,GRAD SCH ENVIRONM EARTH SCI,DIV BIOSCI,CYTOGENET LAB,SAPPORO,HOKKAIDO 060,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RP Nakano, H (reprint author), JUNTENDO UNIV,SCH MED,DEPT IMMUNOL,BUNKYO KU,2-1-1 HONGO,TOKYO 113,JAPAN. OI Nakano, Hiroyasu/0000-0003-4843-1427 FU NCI NIH HHS [CA69381]; NIAID NIH HHS [AI33068] NR 44 TC 11 Z9 12 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAY 15 PY 1997 VL 42 IS 1 BP 26 EP 32 DI 10.1006/geno.1997.4697 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WZ486 UT WOS:A1997WZ48600004 PM 9177772 ER PT J AU Sood, R Blake, T Aksentijevich, I Wood, G Chen, X Gardner, D Shelton, DA Mangelsdorf, M Orsborn, A Pras, E Balow, JE Centola, M Deng, ZM Zaks, N Chen, XG Richards, N FischelGhodsian, N Rotter, JI Pras, M Shohat, M Deaven, LL Gumucio, DL Callen, DF Richards, RI Collins, FS Liu, PP Kastner, DL Doggett, NA AF Sood, R Blake, T Aksentijevich, I Wood, G Chen, X Gardner, D Shelton, DA Mangelsdorf, M Orsborn, A Pras, E Balow, JE Centola, M Deng, ZM Zaks, N Chen, XG Richards, N FischelGhodsian, N Rotter, JI Pras, M Shohat, M Deaven, LL Gumucio, DL Callen, DF Richards, RI Collins, FS Liu, PP Kastner, DL Doggett, NA TI Construction of a 1-Mb restriction-mapped cosmid contig containing the candidate region for the familial mediterranean fever locus (MEFV) on chromosome 16p13.3 SO GENOMICS LA English DT Article ID HIGH GENE-FREQUENCY; PHYSICAL MAP; HUMAN GENOME; HUMAN DNA; SHORT ARM; LIBRARY; RESOLUTION; FRAGMENTS; SEQUENCES; ARMENIANS AB In this paper we describe the assembly and restriction map of a 1.05-Mb cosmid contig spanning the candidate region for familial Mediterranean fever (FMF), a recessively inherited disorder of inflammation localized to 16p13.3. Using a combination of cosmid walking and screening for P1, PAC, BAG, and YAC clones, we have generated a contig of genomic clones spanning similar to 1050 kb that contains the FMF critical region. The map consists of 179 cosmid, 15 P1, 10 PAC, 3 BAG, and 17 YAC clones, anchored by 27 STS markers. Eight additional STSs have been developed from the similar to 700 kb immediately centromeric to this genomic region. Five of the 35 STSs are microsatellites that have not been previously reported. NotI and EcoRI mapping of the overlapping cosmids, hybridization of restriction fragments from cosmids to one another, and STS analyses have been used to validate the assembly of the contig. Our contig totally subsumes the 250-kb interval recently reported, by founder haplotype analysis, to contain the FMF gene. Thus, our high-resolution clone map provides an ideal resource for transcriptional mapping toward the eventual identification of this disease gene. (C) 1997 Academic Press. C1 NIH,NATL CTR HUMAN GENOME RES,LAB GENE TRANSFER,BETHESDA,MD 20892. UNIV MICHIGAN,DEPT ANAT & CELL BIOL,ANN ARBOR,MI 48109. ADELAIDE WOMENS & CHILDRENS HOSP,DEPT CYTOGENET & MOL GENET,ADELAIDE,SA 5006,AUSTRALIA. CEDARS SINAI MED CTR,DEPT PEDIAT,LOS ANGELES,CA 90048. CEDARS SINAI MED CTR,DEPT MED GENET,LOS ANGELES,CA 90048. CHAIM SHEBA MED CTR,HELLER INST MED RES,IL-52621 TEL HASHOMER,ISRAEL. BEILINSON MED CTR,DEPT MED GENET,IL-49100 PETAH TIQWA,ISRAEL. LOS ALAMOS NATL LAB,CTR HUMAN GENOME STUDIES,LOS ALAMOS,NM 87545. RP Sood, R (reprint author), NIAMSD,ARTHRIT & RHEUMATISM BRANCH,NIH,BLDG 10,ROOM 9N-210,BETHESDA,MD 20892, USA. RI Liu, Paul/A-7976-2012; Callen, David/G-1975-2012; Mangelsdorf, Marie/A-2318-2013; OI Liu, Paul/0000-0002-6779-025X; Mangelsdorf, Marie/0000-0002-7855-7701; Callen, David/0000-0002-6189-9991 NR 39 TC 17 Z9 18 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAY 15 PY 1997 VL 42 IS 1 BP 83 EP 95 DI 10.1006/geno.1997.4629 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WZ486 UT WOS:A1997WZ48600011 PM 9177779 ER PT J AU Jensen, SJ Sulman, EP Maris, JM Matise, TC Vojta, PJ Barrett, JC Brodeur, GM White, PS AF Jensen, SJ Sulman, EP Maris, JM Matise, TC Vojta, PJ Barrett, JC Brodeur, GM White, PS TI An integrated transcript map of human chromosome 1p35-p36 SO GENOMICS LA English DT Article ID HUMAN GENOME; LINKAGE MAP; GENETIC-LINKAGE; SHORT ARM; NEUROBLASTOMA; CONSTRUCTION; ASSIGNMENT; DELETION; MARKERS; CELLS AB The distal short arm of human chromosome 1 (Ip) is rearranged in a variety of malignancies, and several genetic diseases also map to this region. We have constructed an integrated transcript map to precisely define the positions of genes and expressed sequence tags (ESTs) previously mapped to 1p35-p36, a region spanning approximately 40 Mb. To anchor the integrated map, a framework genetic map was constructed with 24 genetic markers and a marker order of >1000:1 odds, yielding an average resolution of 2.8 cM. An additional 106 genetic markers were localized relative to the framework genetic map. To place markers more precisely within 1p35-p36, a chromosome 1-specific, radiation-reduced hybrid (RH) panel was created. Individual DNA fragments of the RH panel were identified and ordered by PCR with the framework. genetic map. A total of 250 markers, including 142 genes and ESTs, were mapped by PCR against the RH panel. The map has an observed resolution of 800 kb, and the results closely match and more precisely define previous mapping information for most markers. This map will help to identify candidate genes for genetic diseases mapping to distal Ip and is fully integrated with existing genetic and RH maps of the human genome. (C) 1997 Academic Press. C1 CHILDRENS HOSP,DIV ONCOL,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT PEDIAT,PHILADELPHIA,PA 19104. ROCKEFELLER UNIV,LAB STAT GENET,NEW YORK,NY 10021. NIEHS,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. FU NCI NIH HHS [CA39771]; NHGRI NIH HHS [HG00008] NR 37 TC 35 Z9 35 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAY 15 PY 1997 VL 42 IS 1 BP 126 EP 136 DI 10.1006/geno.1997.4714 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WZ486 UT WOS:A1997WZ48600014 PM 9177782 ER PT J AU Rubanyi, GM Freay, AD Kauser, K Sukovich, D Burton, G Lubahn, DB Couse, JF Curtis, SW Korach, KS AF Rubanyi, GM Freay, AD Kauser, K Sukovich, D Burton, G Lubahn, DB Couse, JF Curtis, SW Korach, KS TI Vascular estrogen receptors and endothelium-derived nitric oxide production in the mouse aorta - Gender difference and effect of estrogen receptor gene disruption SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE estrogen receptor; ERKO mice; I-125-17 beta-estradiol binding; gender difference; nitric oxide synthase ID ATHEROSCLEROTIC CORONARY-ARTERIES; PROGESTERONE RECEPTORS; POSTMENOPAUSAL WOMEN; METHYL-ESTER; FOLLOW-UP; CELLS; HYPERTENSION; INHIBITION; ESTRADIOL; PREGNANCY AB The present study was designed to test the hypothesis that estrogen receptors (ER) in the blood vessel wall play a role in the modulation of the release of endothelium-derived nitric oxide (EDNO). Both basal and stimulated release of EDNO were determined in aortic rings isolated from female and male wild-type and male homozygous estrogen receptor knock-out (ERKO) mice. I-125-17 beta-estradiol binding in aortic tissue showed significantly more high affinity cytosolic-nuclear-binding sites in male compared with female wildtype mice. Estrogen receptor transcripts were present in the aorta of male wild-type mice, but they were absent in male ERKO animals. Basal release of EDNO (determined by endothelium-dependent contraction caused by N-G-nitro-L-arginine) was significantly higher in aorta of wild-type male mice compared with wild-type female mice, and significantly lower in the aorta of male ERKO compared with male wild-type mice. Acetylcholine-induced endothelium-dependent relaxation was similar in all groups studied. No difference was observed in the activity of calcium-dependent nitric oxide synthase in homogenates of lungs and brain taken from male wild-type and ERKO mice. These studies show a significant association between the number of estrogen receptors and basal release of EDNO in the aorta of mice, and suggest that decreased vascular estrogen receptor number may represent a novel risk factor for cardiovascular diseases. C1 NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. SCHERING AG,RES CTR,D-1000 BERLIN,GERMANY. UNIV MISSOURI,DEPT BIOCHEM,COLUMBIA,MO 65211. RP Rubanyi, GM (reprint author), BERLEX BIOSCI,DEPT CARDIOVASC RES,15049 SAN PABLO AVE,RICHMOND,CA 94804, USA. OI Korach, Kenneth/0000-0002-7765-418X NR 43 TC 196 Z9 200 U1 1 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY 15 PY 1997 VL 99 IS 10 BP 2429 EP 2437 DI 10.1172/JCI119426 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XB226 UT WOS:A1997XB22600022 PM 9153286 ER PT J AU DiCola, G Cool, MH Accili, D AF DiCola, G Cool, MH Accili, D TI Hypoglycemic effect of insulin-like growth factor-1 in mice lacking insulin receptors SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE diabetes mellitus; ketoacidosis; mutagenesis; genetics; insulin resistance ID FACTOR-BINDING PROTEIN-1; FATTY-ACID OXIDATION; FACTOR-I RECEPTOR; PHOSPHATIDYLINOSITOL 3'-KINASE; HYBRID RECEPTORS; GLUCOSE-TRANSPORT; SOLEUS MUSCLE; IGF-I; RESISTANCE; IRS-1 AB We have investigated the metabolic actions of recombinant human IGF-1 in mice genetically deficient of insulin receptors (IR-/-). After intraperitoneal administration, IGF-1 caused a prompt and sustained decrease of plasma glucose levels in IR-/- mice, Plasma free fatty acid concentrations were unaffected. Interestingly, the effects of IGF-1 were identical in normal mice (IR+/+) and in IR-/- mice, Despite decreased glucose levels, IR-/- mice treated with IGF-1 died within 2-3 d of birth, like sham-treated IR-/- controls. In skeletal muscle, IGF-1 treatment caused phosphorylation of IGF-1 receptors and increased the levels of the phosphatidylinositol-3-kinase p85 subunit detected in antiphosphotyrosine immunoprecipitates, consistent with the possibility that IGF-1 stimulates glucose uptake in a phosphatidylinositol-3-kinase-dependent manner. IGF-1 receptor phosphorylation and coimmunoprecipitation of phosphatidylinositol-3-kinase by antiphosphotyrosine antibodies was also observed in liver, and was associated with a decrease in mRNA levels of the key gluconeogenetic enzyme phosphoenolpyruvate carboxykinase, Thus, the effect of IGF-1 on plasma glucose levels may be accounted for by increased peripheral glucose use and by inhibition of hepatic gluconeogenesis, These data indicate that IGF-1 can mimic insulin's effects on glucose metabolism by acting through its own receptor, The failure of IGF-1 to rescue the lethal phenotype due to lack of insulin receptors suggests that IGF-1 receptors cannot effectively mediate all the metabolic actions of insulin receptors. C1 NICHHD,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. NR 57 TC 99 Z9 99 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY 15 PY 1997 VL 99 IS 10 BP 2538 EP 2544 DI 10.1172/JCI119438 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XB226 UT WOS:A1997XB22600034 PM 9153298 ER PT J AU delaSalle, H Houssaint, E Peyrat, MA Arnold, D Salamero, J Pinczon, D Stevanovic, S Bausinger, H Fricker, D Gomard, E Biddison, W Lehner, P UytdeHaag, F Sasportes, M Donato, L Rammensee, HG Cazenave, JP Hanau, D Tongio, MM Bonneville, M AF delaSalle, H Houssaint, E Peyrat, MA Arnold, D Salamero, J Pinczon, D Stevanovic, S Bausinger, H Fricker, D Gomard, E Biddison, W Lehner, P UytdeHaag, F Sasportes, M Donato, L Rammensee, HG Cazenave, JP Hanau, D Tongio, MM Bonneville, M TI Human peptide transporter deficiency - Importance of HLA-B in the presentation of TAP-independent EBV antigens SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOTOXIC LYMPHOCYTES-T; CLASS-I; MUTANT MICE; CELL-LINE; GENE; MOLECULES; REACTIVITY; SELECTION; PROTEINS; MUTATION AB Two siblings with a peptide TAP deficiency were recently described, Despite poor cell surface expression of HLA class I molecules, these patients were not unusually susceptible to viral infections, The majority of the cell surface-expressed class I molecules were HLA-B products as assessed by cytofluorometry and biochemical analysis, Analysis of two peptides eluted from the class I molecules expressed by TAP-deficient EBV B lymphoblastoid cell lines indicated that both were derived from cytosolic proteins and presented by HLA-B molecules, Peripheral alpha beta CD8(+) T cells were present and their TCR repertoire was polyclonal, Most of the alpha beta CD8(+) T cell clones studied (21 of 22) were nonreactive against cells expressing normal levels of the same HLA alleles as those of the TAP-deficient patients. However, it was possible to isolate one cytotoxic CD8(+) alpha beta T cell clone recognizing the EBV protein LMP2 presented by HLA-B molecules on TAP-deficient cells, These observations suggest that in the TAP-deficient patients, CD8(+) alpha beta T cells could mature and be recruited in immune responses to mediate HLA class I-restricted cytotoxic defense against viral infections, They also strengthen the physiologic importance of a TAP-independent processing pathway of the LMP2 protein, which was previously shown to contain several other TAP-independent epitopes. C1 INSERM,HISTOCOMPATIBIL LAB,CONTRACT YOUNG RES UNIT 9403,STRASBOURG,FRANCE. BLOOD TRANSFUS ESTAB,INSERM,U311,STRASBOURG,FRANCE. INST BIOL,INSERM,U211,NANTES,FRANCE. CANC RES INST,HEIDELBERG,GERMANY. INST CURIE,MINTE UNIT RES 144,PARIS,FRANCE. INST COCHIN GENET MOL,INSERM,U152,F-75014 PARIS,FRANCE. NINCDS,MOL IMMUNOL SECT,DEPT NEUROIMMUNOL,NIH,BETHESDA,MD 20892. UNIV CARDIFF,DEPT MED,CARDIFF,S GLAM,WALES. ERASMUS UNIV ROTTERDAM,DEPT VIROL,NL-3000 DR ROTTERDAM,NETHERLANDS. ST LOUIS HOSP,HAYEM CTR,INSERM,U93,PARIS,FRANCE. HAUTEPIERRE HOSP,SERV PEDIAT,STRASBOURG,FRANCE. RI De La Salle, Henri/H-9353-2016 OI De La Salle, Henri/0000-0001-5136-0776 NR 37 TC 31 Z9 33 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1997 VL 158 IS 10 BP 4555 EP 4563 PG 9 WC Immunology SC Immunology GA WX987 UT WOS:A1997WX98700007 PM 9144467 ER PT J AU Doherty, TM Sher, A AF Doherty, TM Sher, A TI Defects in cell-mediated immunity affect chronic, but not innate, resistance of mice to Mycobacterium avium infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE SYNTHASE; FACTOR-ALPHA PRODUCTION; INTERFERON-GAMMA; HUMAN MACROPHAGES; HUMAN MONOCYTES; INTRACELLULARE COMPLEX; ALVEOLAR MACROPHAGES; CYTOKINE EXPRESSION; MURINE MACROPHAGES AB To investigate the role of cell-mediated immunity in the control of Mycobacterium avium infection, we studied the effects of targeted gene disruptions in components of the T lymphocyte-dependent, macrophage-mediated response on resistance of mice to this pathogen. Normal mice developed a chronic, asymptomatic infection, with rapid induction of mRNAs for IFN-gamma, IL-12, and TNF-alpha in spleen, liver, and lung. Bacterial loads in gene knockout, scid, and wild-type mice were indistinguishable for the first 4 wk of infection. However, by 8 wk postinfection, scid mice as well as animals with a targeted disruption of the IFN-gamma gene showed enhanced bacterial growth compared with wild-type controls. In contrast, knockout mice lacking the genes for the TNF-alpha p55/p75 receptors or inducible nitric oxide synthase not only developed comparable bacterial loads to wild-type animals they also failed to display the splenomegaly and profound suppression of mitogen-induced lymphocyte proliferative responses evident in infected wild-type controls. Thus, M. avium is clearly distinct from other intracellular pathogens (e.g., Leishmania monocytogenes. Toxoplasma gondii, and Mycobacterium tuberculosis) whose initial replication in the host is tightly controlled by Th1-dependent effector mechanisms. Instead, the major effect of host cell-mediated immunity is to limit bacterial growth during the chronic phase of infection. Surprisingly, inducible nitric oxide appears to be more important for the immunopathology than for the host resistance induced by this bacterial pathogen. RP Doherty, TM (reprint author), NIAID,IMMUNOBIOL SECT,PARASIT DIS LAB,NIH,BLDG 4,ROOM B1-06,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 71 TC 89 Z9 89 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1997 VL 158 IS 10 BP 4822 EP 4831 PG 10 WC Immunology SC Immunology GA WX987 UT WOS:A1997WX98700037 PM 9144497 ER PT J AU Zhang, L Yoshimura, T Graves, DT AF Zhang, L Yoshimura, T Graves, DT TI Antibody to Mac-1 or monocyte chemoattractant protein-1 inhibits monocyte recruitment and promotes tumor growth SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MACROPHAGE INFILTRATION; BLOOD MONOCYTES; MALIGNANT-CELLS; MESSENGER-RNA; EXPRESSION; CANCER; INVIVO; MELANOMA; RECEPTOR; ADHESION AB Human tumors are frequently infiltrated by numerous monocytes/macrophages, which can be found within the tumor mass (intratumoral) or surrounding the tumor (peritumoral). The functional role that these monocytes/macrophages play in tumor growth is controversial. To address this issue we inhibited intratumoral monocyte/macrophage recruitment with mAbs that either blocked integrin function or neutralized a tumor-produced chemotactic protein. Both treatments significantly increased tumor formation and accelerated tumor growth. Surprisingly, the same results were obtained when recruitment of peritumoral or intratumoral monocytes/macrophages was blocked. Our findings are contrary to one of the purported roles of monocytes/macrophages, particularly in the peritumoral area, since we found no evidence for monocyte/macrophage-supported tumor growth. These results provide direct evidence that intratumoral as well as peritumoral monocytes/macrophages act to limit tumor size in the early stages following tumor inoculation and provide a mechanism that accounts for monocyte/macrophage recruitment to human tumors. C1 BOSTON UNIV, MED CTR,DIV ORAL BIOL,SCH MED, DEPT PATHOL & LAB MED, BOSTON, MA 02118 USA. NCI, IMMUNOPATHOL SECT, IMMUNOBIOL LAB, FREDERICK CANC RES & DEV CTR, FREDERICK, MD 21702 USA. BOSTON UNIV, SCH DENT MED, DIV ORAL BIOL, BOSTON, MA 02118 USA. FU NIDCR NIH HHS [DE-07559] NR 42 TC 28 Z9 29 U1 2 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1997 VL 158 IS 10 BP 4855 EP 4861 PG 7 WC Immunology SC Immunology GA WX987 UT WOS:A1997WX98700041 PM 9144501 ER PT J AU Zhang, C Hirasawa, N Beaven, MA AF Zhang, C Hirasawa, N Beaven, MA TI Antigen activation of mitogen-activated protein kinase in mast cells through protein kinase C-dependent and independent pathways SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; RECEPTOR TYROSINE KINASE; EPIDERMAL GROWTH-FACTOR; GRB2 ADAPTER PROTEIN; RBL-2H3 CELLS; MAP KINASE; CROSS-LINKING; TRANSCRIPTION FACTOR; SIGNAL-TRANSDUCTION; SYNERGISTIC SIGNALS AB We demonstrate discrete pathways for activation of mitogen-activated protein (MAP) kinase in cultured RBL-2H3 mast cells through protein kinase C (PKC), cytosolic calcium, and a third pathway that provides sustained signals for activation in Ag-stimulated cells. Thus, p42 MAP kinase was activated by increasing intracellular free Ca2+ with thapsigargin or by stimulating PKC with PMA. The latter stimulation was selectively blocked by the protein kinase C inhibitor, Ro31-7549. Stimulation of p42 MAP kinase by Ag resulted in relatively sustained activation of MAP kinase which was only partially suppressed by Ro31-7549. Kinetic studies revealed two components of the MAP kinase response to Ag: a rapid but transient component that was Ro31-7549 sensitive and presumably PKC dependent; and a more sustained component that was Ro31-7549 resistant and presumably PKC independent. Similarly, Ro31-7549 inhibited the early but not late release of arachidonic acid, a finding that was consistent with the known regulation of phospholipase A(2) by MAP kinase. Early tyrosine phosphorylation events which were thought to be essential for Ag-induced activation of p42 MAP kinase and release of arachidonic acid were unaffected by Ro31-7549. The findings suggested that release of arachidonic acid was regulated primarily through MAP kinase but that PKC may transiently influence this release, either directly or indirectly through MAP kinase. C1 NHLBI,MOL IMMUNOL LAB,NIH,BETHESDA,MD 20892. NR 45 TC 31 Z9 31 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1997 VL 158 IS 10 BP 4968 EP 4975 PG 8 WC Immunology SC Immunology GA WX987 UT WOS:A1997WX98700056 PM 9144516 ER PT J AU Warren, MK Rose, WL Cone, JL Rice, WG Turpin, JA AF Warren, MK Rose, WL Cone, JL Rice, WG Turpin, JA TI Differential infection of CD34(+) cell-derived dendritic cells and monocytes with lymphocyte-tropic and monocyte-tropic HIV-1 strains SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; COLONY-STIMULATING FACTOR; TUMOR-NECROSIS-FACTOR; MONONUCLEAR PHAGOCYTES; PROGENITOR CELLS; BONE-MARROW; T-CELLS; MACROPHAGE; TYPE-1; IDENTIFICATION AB Monocytes and dendritic cells are infected by HIV-1 and subsequently produce virions that initiate further rounds of infection. Current methods for the isolation and study of dendritic tells are hampered by the low frequency of these cells and contamination with other cell types. A two-step culture method was devised to generate large numbers of either dendritic cells or monocytes from fetal liver CD34(+) progenitors. CD34(+) cells were first expanded with the growth factors granulocyte-macrophage CSF and stem cell factor to generate a population of intermediate progenitor cells with a relatively immature phenotype. To induce specific differentiation to dendritic cells, the cultures were switched to serum-free medium with the growth factors granulocyte-macrophage CSF, stem cell factor, TNF-alpha, and IL-4. The cells became highly positive for HLA class II Ags and the dendritic cell marker CD1a. Culture of the intermediate progenitors in serum-containing medium with macrophage CSF resulted in differentiation to adherent monocytes expressing high levels of CD14 with low CD1a expression. The intermediate progenitors were permissive for HIV infection by both monocyte- and lymphocyte-tropic strains. In contrast, differentiation to monocytes or dendritic cells resulted in restricted viral tropism. Dendritic cells efficiently replicated the lymphocyte-tropic virus HIV-1(MN), but not the monocyte-tropic virus HIV-1(ADA). As expected, monocytes only supported replication of HIV-1(ADA). This two-step culture method allows for the production of large numbers of monocytes or dendritic cells from a common precursor pool for studying the development of tropism-associated events. C1 NCI,LAB ANTIVIRAL DRUG MECHANISMS,SAIC FREDERICK,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. OTSUKA AMER PHARMACEUT INC,ROCKVILLE,MD 20852. RP Warren, MK (reprint author), POIET TECHNOL INC,904 WIND RIVER LANE 102,GAITHERSBURG,MD 20878, USA. NR 53 TC 23 Z9 23 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1997 VL 158 IS 10 BP 5035 EP 5042 PG 8 WC Immunology SC Immunology GA WX987 UT WOS:A1997WX98700064 PM 9144524 ER PT J AU Keros, S McBain, CJ AF Keros, S McBain, CJ TI Arachidonic acid inhibits transient potassium currents and broadens action potentials during electrographic seizures in hippocampal pyramidal and inhibitory interneurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE arachidonate; potassium currents; stratum oriens interneurons; fatty acids; interictal spikes; CA1 ID SYNAPTIC TRANSMISSION; FATTY-ACIDS; STRIATAL NEURONS; RAT HIPPOCAMPUS; 2ND MESSENGERS; ION CHANNELS; RELEASE; CELLS; METABOLITES; RECEPTORS AB The transient outward potassium current was studied in outside-out macropatches excised from the soma of CA? pyramidal neurons and stratum (st.) oriens-alveus inhibitory interneurons in rat hippocampal slices, Arachidonic acid dose dependently decreased the charge transfer associated with the transient current, concomitant with an increase in the rate of current inactivation. Arachidonic acid (AA) did not affect the voltage dependence of steady state inactivation but did prolong the period required for complete recovery from inactivation. The effects of AA were mimicked by the nonmetabolizable analog of AA, 5,8,11,14-eicosatetraynoic acid, suggesting that metabolic products of AA were not responsible for the observed blocking action, In addition, AA blocked st. oriensalveus-lacunosum-moleculare interneuron transient currents but not currents recorded from basket cell interneurons. In current clamp experiments, AA was without effect on the action potential waveform of CA1 pyramidal neurons under control recording conditions. In voltage-clamp experiments, the use of a test pulse paradigm, designed to mimic the action potential voltage trajectory, revealed that the transient current normally associated with a single spike deactivates too rapidly for AA to have an effect. Transient currents activated by longer duration ''action potential'' waveforms, however, were attenuated by AA. Consistent with this finding was the observation that AA broadened interictal spikes recorded in the elevated [K+](o) model of epilepsy. These data suggest that AA liberated from hippocampal neurons may act to block the transient current selectively in both CA1 pyramidal neurons and inhibitory interneurons and to broaden action potentials selectively under pathological conditions. C1 NICHHD,NIH,CELLULAR & MOL BIOL LAB,BETHESDA,MD 20892. NR 50 TC 57 Z9 58 U1 1 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 15 PY 1997 VL 17 IS 10 BP 3476 EP 3487 PG 12 WC Neurosciences SC Neurosciences & Neurology GA WX661 UT WOS:A1997WX66100010 PM 9133373 ER PT J AU Nicolaou, KC Winssinger, N Pastor, J Ninkovic, S Sarabia, F He, Y Vourloumis, D Yang, Z Li, T Giannakakou, P Hamel, E AF Nicolaou, KC Winssinger, N Pastor, J Ninkovic, S Sarabia, F He, Y Vourloumis, D Yang, Z Li, T Giannakakou, P Hamel, E TI Synthesis of epothilones A and B in solid and solution phase SO NATURE LA English DT Article ID TAXOL AB Epothilones A and B, two compounds that have been recently isolated(1) from myxobacterium Sorangium cellulosum strain 90, have generated intense interest(2-16) among chemists, biologists and clinicians erring to the structural complexity, unusual mechanism of interaction with microtubules and anticancer potential of these molecules. Like taxol* (refs 17, 18), they exhibit cytotoxicity against tumour cells by inducing microtubule assembly and stabilization(3,4), even in taxol-resistant cell lines. Following the structural elucidation of these molecules by X-ray crystallography in 1996(1), several syntheses of epothilones A (refs 12-16) and B (ref. 19) have been reported, indicative of the potential importance of these molecules in the cancer field. Here we report the first solid-phase synthesis of epothilone A, the total synthesis of epothilone B, and the generation of a small epothilone library. The solid-phase synthesis applied here to epothilone A could open up new possibilities in natural-product synthesis and, together with solution-phase synthesis of other epothilones, paves the way for the generation of large combinatorial libraries of these important molecules for biological screening. C1 Scripps Res Inst, SKAGGS INST CHEM BIOL, LA JOLLA, CA 92037 USA. UNIV CALIF SAN DIEGO, DEPT CHEM & BIOCHEM, LA JOLLA, CA 92093 USA. NCI, MED BRANCH, DCS, NIH, BETHESDA, MD 20892 USA. NCI, LAB DRUG DISCOVERY RES & DEV,DEV THERAPEUT PROGRAM, DCTDC,FREDERICK CANC RES & DEV CTR, FREDERICK, MD 21702 USA. RP Nicolaou, KC (reprint author), Scripps Res Inst, DEPT CHEM, 10550 N TORREY PINES RD, LA JOLLA, CA 92037 USA. RI Li, Tianhu/G-3531-2010; Sarabia, Francisco/M-1845-2014; Pastor, Joaquin/I-4567-2015; Yang, Zhen/J-6306-2015; Winssinger, Nicolas/B-6710-2017 OI Sarabia, Francisco/0000-0002-5149-3576; Pastor, Joaquin/0000-0003-0553-8021; Yang, Zhen/0000-0001-8036-934X; Winssinger, Nicolas/0000-0003-1636-7766 NR 31 TC 342 Z9 350 U1 4 U2 45 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD MAY 15 PY 1997 VL 387 IS 6630 BP 268 EP 272 DI 10.1038/387268a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WZ167 UT WOS:A1997WZ16700048 PM 9153390 ER PT J AU Kubbutat, MHG Jones, SN Vousden, KH AF Kubbutat, MHG Jones, SN Vousden, KH TI Regulation of p53 stability by Mdm2 SO NATURE LA English DT Article ID EMBRYONIC LETHALITY; MDM2-DEFICIENT MICE; ONCOPROTEIN MDM2; PROTEIN; DOMAIN; TRANSACTIVATION; DEGRADATION; EXPRESSION; ACTIVATION; BINDING AB The tumour-suppressor p53 is a short-lived protein that is maintained at low, often undetectable, levels in normal cells. Stabilization of the protein in response to an activating signal, such as DNA damage, results in a rapid rise in p53 levels and subsequent inhibition of cell growth(1). Tight regulation of p53 function is critical for normal cell growth and development, and one mechanism by which p53 function is controlled is through interaction with the Mdm2 protein(2-4). Mdm2 inhibits p53 cell-cycle arrest and apoptic functions(5,6) and we show here that interaction with Mdm2 can also result in a large reduction in p53 protein levels through enhanced proteasome-dependent degradation. Endogenous levels of Mdm2 are sufficient to regulate p53 stability, and overexpression of Mdm2 can reduce the amount of endogenous p53. Because mdm2 is transcriptionally activated by p53 (refs 7, 8), this degradative pathway may contribute to the maintenance of low p53 concentrations in normal cells. Furthermore, mechanisms regulating the Mdm2-induced degradation of p53 may play a role in controlling the extent and duration of the p53 response. C1 NCI,ABL BASIC RES PROGRAM,FCRDC,FREDERICK,MD 21701. BAYLOR COLL MED,DEPT MOL & HUMAN GENET,HOUSTON,TX 77030. NR 30 TC 2259 Z9 2293 U1 11 U2 109 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD MAY 15 PY 1997 VL 387 IS 6630 BP 299 EP 303 DI 10.1038/387299a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WZ167 UT WOS:A1997WZ16700057 PM 9153396 ER PT J AU Struewing, JP Hartge, P Wacholder, S Baker, SM Berlin, M McAdams, M Timmerman, MM Brody, LC Tucker, MA AF Struewing, JP Hartge, P Wacholder, S Baker, SM Berlin, M McAdams, M Timmerman, MM Brody, LC Tucker, MA TI The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BREAST-CANCER; OVARIAN-CANCER; SUSCEPTIBILITY GENE; FAMILIES; CARRIERS; WOMEN AB Background Carriers of germ-line mutations in BRCA1 and BRCA2 from families at high risk for cancer have been estimated to have an 85 percent risk of breast cancer. Since the combined frequency of BRCA1 and BRCA2 mutations exceeds 2 percent among Ashkenazi Jews, we were able to estimate the risk of cancer in a large group of Jewish men and women from the Washington, D.C., area. Methods We collected blood samples from 5318 Jewish subjects who had filled out epidemiologic questionnaires. Carriers of the 185delAG and 5382insC mutations in BRCA1 and the 6174delT mutation in BRCA2 were identified with assays based on the polymerase chain reaction. We estimated the risks of breast and other cancers by comparing the cancer histories of relatives of carriers of the mutations and noncarriers. Results One hundred twenty carriers of a BRCA1 or BRCA2 mutation were identified. By the age of 70, the estimated risk of breast cancer among carriers was 56 percent (95 percent confidence interval, 40 to 73 percent); of ovarian cancer, 16 percent (95 percent confidence interval, 6 to 28 percent); and of prostate cancer, 16 percent (95 percent confidence interval, 4 to 30 percent). There were no significant differences in the risk of breast cancer between carriers of BRCA1 mutations and carriers of BRCA2 mutations, and the incidence of colon cancer among the relatives of carriers was not elevated. Conclusions Over 2 percent of Ashkenazi Jews carry mutations in BRCA1 or BRCA2 that confer increased risks of breast, ovarian, and prostate cancer. The risks of breast cancer may be overestimated, but they fall well below previous estimates based on subjects from high-risk families. (C) 1997, Massachusetts Medical Society. C1 NATL CANC INST,DIV CANC EPIDEMIOL & GENET,NIH,BETHESDA,MD. NATL HUMAN GENOME RES INST,LAB GENE TRANSFER,NIH,BETHESDA,MD. WESTAT CORP,ROCKVILLE,MD. IMS INC,SILVER SPRING,MD. RI Struewing, Jeffery/C-3221-2008; Tucker, Margaret/B-4297-2015; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 NR 34 TC 1443 Z9 1474 U1 1 U2 48 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 15 PY 1997 VL 336 IS 20 BP 1401 EP 1408 DI 10.1056/NEJM199705153362001 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA WY577 UT WOS:A1997WY57700001 PM 9145676 ER PT J AU Straus, SE Lenardo, M Puck, JM AF Straus, SE Lenardo, M Puck, JM TI The Canale-Smith syndrome SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID LYMPHOPROLIFERATIVE SYNDROME; MUTATIONS C1 NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP Straus, SE (reprint author), NIAID,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 15 PY 1997 VL 336 IS 20 BP 1457 EP 1457 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA WY577 UT WOS:A1997WY57700026 PM 9148156 ER PT J AU Kalinina, O Lebedeva, I Brown, J Silver, J AF Kalinina, O Lebedeva, I Brown, J Silver, J TI Nanoliter scale PCR with TaqMan detection SO NUCLEIC ACIDS RESEARCH LA English DT Article ID POLYMERASE CHAIN-REACTION; MESSENGER-RNA; DNA; AMPLIFICATION; PRODUCT AB We monitored PCR in volumes of the order of 10 nl in glass microcapillaries using a fluorescence energy transfer assay in which fluorescence increases if product is made due to template-dependent nucleolytic degradation of an internally quenched probe (TaqMan assay). This assay detected single starting template molecules in dilutions of genomic DNA. The results suggest that it may be feasible to determine the number of template molecules in a sample by counting the number of positive PCRs in a set of replicate reactions using terminally diluted sample. Since the assay system is closed and potentially automatable, it has promise for clinical applications. C1 NIAID,MOL MICROBIOL LAB,NIH,BETHESDA,MD 20892. CYTONIX CORP,BELTSVILLE,MD. NR 18 TC 130 Z9 140 U1 2 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY 15 PY 1997 VL 25 IS 10 BP 1999 EP 2004 DI 10.1093/nar/25.10.1999 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WZ939 UT WOS:A1997WZ93900017 PM 9115368 ER PT J AU Craig, C Wersto, R Kim, M Ohri, E Li, ZW Katayose, D Lee, SJ Trepel, J Cowan, K Seth, P AF Craig, C Wersto, R Kim, M Ohri, E Li, ZW Katayose, D Lee, SJ Trepel, J Cowan, K Seth, P TI A recombinant adenovirus expressing p27(Kip1) induces cell cycle arrest and lass of cyclin-Cdk activity in human breast cancer cells SO ONCOGENE LA English DT Article DE cyclin kinase inhibitors; cell growth; cell cycle; G(1)/S arrest ID DEPENDENT KINASE INHIBITOR; POTENTIAL MEDIATOR; P21; P16; GROWTH AB In order to elucidate the biochemical mechanisms by which the universal cyclin kinase inhibitor p27(Kip1) regulates cell cycle progression in human breast cancer cells, a recombinant adenovirus expressing human p27 was constructed (Adp27). Upon infection of human breast cancer cells MDA-MB-231 and MCF-7 with Adp27, a high level of p27 expression was observed, and this resulted in a marked decrease in the proportion of cells in S-phase, In multiple cell lines, comparison of the cytotoxicity of Adp27 with another adenovirus vector expressing the related universal cyclin kinase inhibitor WAF1/Cip1 (AdWAF1), showed Adp27 to be markedly more (up to 56-fold) toxic than AdWAF1, DNA histograms showed Adp27 to cause a G(1)/S arrest at lower viral doses than AdWAF1, Analysis of cyclin dependent kinase activity following Adp27 infections showed decreased Cdk2 and cyclin B1-Cdc2 activity at lower viral doses when compared with AdWAF1, Adp27 is therefore potentially useful for studies of growth regulation and for gene therapy when growth inhibition is desired. C1 NCI,MED BRANCH,NIH,BETHESDA,MD 20892. NCI,PATHOL BRANCH,NIH,BETHESDA,MD 20892. NR 28 TC 179 Z9 185 U1 1 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 15 PY 1997 VL 14 IS 19 BP 2283 EP 2289 DI 10.1038/sj.onc.1201064 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA WY883 UT WOS:A1997WY88300005 PM 9178904 ER PT J AU Kidder, LH Levin, IW Lewis, EN Kleiman, VD Heilweil, EJ AF Kidder, LH Levin, IW Lewis, EN Kleiman, VD Heilweil, EJ TI Mercury cadmium telluride focal-plane array detection for mid-infrared Fourier-transform spectroscopic imaging SO OPTICS LETTERS LA English DT Article ID MICROSCOPY AB By combining step-scan Fourier-transform Michelson interferometry, an infrared microscope, and mercury cadmium telluride focal-plane array image detection we have constructed a mid-infrared spectroscopic imaging system that simultaneously records high-fidelity images and spectra of materials from 3500 to 900 cm(-1) (2.8 to 11 mu m) at a variety of spectral resolutions. The fidelity of the spectral images is determined by the pixel number density of the focal-plane array. Step-scan imaging principles and instrument design details are outlined. Spatial resolution measurements and infrared chemical imaging examples are presented, and the results are discussed with respect to implications for chemical analysis of biosystems and composite materials. (C) 1997 Optical Society of America. C1 NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. NIST,OPT TECHNOL DIV,GAITHERSBURG,MD 20899. RI Kleiman, Valeria/H-7818-2013 OI Kleiman, Valeria/0000-0002-9975-6558 NR 14 TC 52 Z9 52 U1 2 U2 8 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD MAY 15 PY 1997 VL 22 IS 10 BP 742 EP 744 DI 10.1364/OL.22.000742 PG 3 WC Optics SC Optics GA XA242 UT WOS:A1997XA24200027 PM 18185647 ER PT J AU Fechner, JH Vargo, DJ Geissler, EK Graeb, C Wang, J Hanaway, MJ Watkins, DI Piekarczyk, M Neville, DM Knechtle, SJ AF Fechner, JH Vargo, DJ Geissler, EK Graeb, C Wang, J Hanaway, MJ Watkins, DI Piekarczyk, M Neville, DM Knechtle, SJ TI Split tolerance induced by immunotoxin in a rhesus kidney allograft model SO TRANSPLANTATION LA English DT Article ID DONOR BONE-MARROW; MAJOR HISTOCOMPATIBILITY COMPLEX; TRANSPLANTATION TOLERANCE; RENAL-ALLOGRAFT; VETO CELLS; T-CELLS; INTRATHYMIC INOCULATION; LIVER-TRANSPLANTATION; PERIPHERAL TOLERANCE; SOLUBLE ALLOANTIGENS AB Background. Renal allografts were performed in rhesus monkeys using FN18-CRM9, a potent immunotoxin capable of depleting T cells to less than 1% of baseline levels in blood and lymph nodes, as a preparative agent. We have recently reported that animals pretreated with FN18-CRM9 1 week before transplantation without further immunosuppression had prolonged graft survival time compared with control animals, and frequently became tolerant. Methods. This report examines the alloimmune responses of recipient monkeys to the donor, including cytotoxic T lymphocyte precursor (CTLp) frequency, mixed lymphocyte response, and antidonor IgG response. Results. CTLp frequencies declined significantly (P<0.01) after FN18-CRM9 treatment and renal transplantation. This decline in CTLp was initially nonspecific, as CTLp frequencies against third-party animals also declined (P<0.01). The decrease in CTLp was maintained in five of five animals tested 6 months after transplant. However, unresponsiveness was limited to the CTL arm of the immune response as antidonor IgG was detected in four of four animals tested, and the 5-day mixed lymphocyte response stimulation index and relative response were not significantly different before and after transplant. In long-term survivors (>150 days), an increase in anti-third-party CTLp was detected 1 month after grafting with third-party skin0 No change was seen in the antidonor CTLp frequency after donor skin grafting, indicating that a specific defect in the antidonor CTL response had developed. Conclusions. These data suggest that FN18-CRM9 treatment of rhesus monkeys allows the development of specific down-regulation of antidonor CTL activity in renal allograft recipients. C1 UNIV WISCONSIN,SCH MED,DEPT SURG,MADISON,WI 53792. UNIV WISCONSIN,SCH MED,DEPT LAB MED & PATHOL,MADISON,WI 53792. UNIV WISCONSIN,WISCONSIN REG PRIMATE RES CTR,MADISON,WI 53792. NIMH,MOL BIOL LAB,BETHESDA,MD 20892. RI Fechner, John/C-5962-2016; Geissler, Edward/R-4131-2016 OI Fechner, John/0000-0002-8220-7237; FU NCRR NIH HHS [RR00167]; NIAID NIH HHS [AI31426] NR 50 TC 43 Z9 44 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 1997 VL 63 IS 9 BP 1339 EP 1345 DI 10.1097/00007890-199705150-00023 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA WZ231 UT WOS:A1997WZ23100023 PM 9158030 ER PT J AU Sikorski, R Peters, R AF Sikorski, R Peters, R TI Oncology ASAP - Where to find reliable cancer information on the Internet SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP Sikorski, R (reprint author), NCI,BLDG 49,4B56,BETHESDA,MD 20892, USA. NR 2 TC 12 Z9 12 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 14 PY 1997 VL 277 IS 18 BP 1431 EP 1432 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA WX852 UT WOS:A1997WX85200012 PM 9145704 ER PT J AU Tucker, MA Halpern, A Holly, EA Hartge, P Elder, DE Sagebiel, RW Guerry, D Clark, WH AF Tucker, MA Halpern, A Holly, EA Hartge, P Elder, DE Sagebiel, RW Guerry, D Clark, WH TI Clinically recognized dysplastic nevi - A central risk factor for cutaneous melanoma SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID FAMILIAL MALIGNANT-MELANOMA; ATYPICAL-MOLE SYNDROME; TUMOR PROGRESSION; GENETIC-HETEROGENEITY; MELANOCYTIC NEVI; NONFAMILIAL MELANOMA; PRECURSOR LESIONS; POPULATION; ASSOCIATION; PHENOTYPE AB Objective.-To investigate the relationship of number and type of nevi to the development of melanoma. Design.-Case-control study. Setting.-Outpatient clinics in referral hospitals. Patients.-Cases were 716 consecutive patients with newly diagnosed melanoma identified at 2 melanoma centers between January 1, 1991, and December 31, 1992. Stratified random sampling of patients from outpatient clinics was used to identify 1014 participating controls of the same age, sex, race, and geographic distribution as the melanoma cases. All study subjects underwent an interview, a complete skin examination, photography of the most atypical nevi, and, if the patient was willing, a biopsy of the most atypical nevus. Main Outcome Measures.-Number and type of nevi on the entire body were systematically reported. All diagnoses of clinically dysplastic nevi were confirmed by expert examiners. Results.-Risk for melanoma was strongly related to number of small nevi, large nondysplastic nevi, and clinically dysplastic nevi. In the absence of dysplastic nevi, increased numbers of small nevi were associated with an approximately 2-fold risk, and increased numbers of both small and large nondysplastic nevi were associated with a 4-fold risk. One clinically dysplastic nevus was associated with a 2-fold risk (95% confidence interval, 1.4-3.6), while 10 or more conferred a 12-fold increased risk (95% confidence interval, 4.4-31). Congenital nevi were not associated with increased risk of melanoma. Conclusions.-Although nondysplastic nevi confer a small risk, clinically dysplastic nevi confer substantial risk for melanoma. On the basis of nevus number and type, clinicians can identify a population at high risk of this epidemic cancer for screening and intervention. C1 NCI,ENVIRONM EPIDEMIOL BRANCH,NIH,BETHESDA,MD 20892. UNIV PENN,SCH MED,PIGMENTED LES STUDY GRP,PHILADELPHIA,PA 19104. UNIV CALIF SAN FRANCISCO,DEPT EPIDEMIOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,MELANOMA CLIN,SAN FRANCISCO,CA 94143. RP Tucker, MA (reprint author), NCI,GENET EPIDEMIOL BRANCH,NIH,EXECUT PLAXA N,SUITE 439,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. RI Tucker, Margaret/B-4297-2015 NR 44 TC 267 Z9 268 U1 0 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 14 PY 1997 VL 277 IS 18 BP 1439 EP 1444 DI 10.1001/jama.277.18.1439 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA WX852 UT WOS:A1997WX85200027 PM 9145715 ER PT J AU Carter, HB Epstein, JI Chan, DW Fozard, JL Pearson, JD AF Carter, HB Epstein, JI Chan, DW Fozard, JL Pearson, JD TI Recommended prostate-specific antigen testing intervals for the detection of curable prostate cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID TUMOR VOLUME; MEN; PROGRESSION AB Objective.-To evaluate prostate-specific antigen (PSA) testing intervals that maintain the detection of curable cancer and reduce unnecessary testing. Design and Patients.-Historical prospective study of serial PSA measurements at 2- and 4-year intervals from frozen serum samples of 40 men who eventually developed prostate cancer and 272 men without prostate cancer who were participants in a prospective aging study (Gerontology Research Center of the National Institute on Aging, the Baltimore Longitudinal Study of Aging) and the case series of 389 consecutive men treated surgically for nonpalpable prostate cancer. Main Outcome Measures.-Probability of a PSA conversion to 4.1 to 5.0 ng/mL and to greater than 5.0 ng/mL at 2 and 4 years and probability of detecting curable prostate cancer by age and PSA level. Results.-When the pretreatment PSA level was less than or equal to 4.0 ng/mL, nonpalpable prostate cancers were highly likely (34/36, 94%) to be curable (organ-confined or capsular penetration with Gleason score <7 and negative margins), and the majority (25/36, 69%) were small cancers (confined tumor less than or equal to 0.5 cm(3) with no Gleason pattern 4 or 5). When the pretreatment PSA level was greater than 4.0 ng/mL and less than or equal to 5.0 ng/mL, cancers were highly likely to be curable (32/36, 89%), and a minority were small cancers (12/36, 33%), When the pretreatment PSA level was greater than 5.0 ng/mL, 96 (30%) of 317 cancers were noncurable. The PSA conversion (for cancer cases) to a level at which cure is less likely (>5.0 ng/mL) is rare (0%) after 2 or 4 years when the initial PSA is less than 2.0 ng/mL. PSA conversion to a range at which cancers are likely to be curable and less likely to be small (4.1-5.0 ng/mL) is rare after 2 years (0%-4%) when the baseline PSA level is less than 2.0 ng/mL but common when the baseline PSA level is between 2.1 and 3.0 ng/mL (27%) or 3.1 and 4.0 ng/mL (36%). Conclusions.-These data suggest that for men with no cancer suspected on digital rectal examination, a PSA level of 4.0 to 5.0 ng/mL is an acceptable range for maintaining the detection of curable prostate cancer and a 2-year PSA testing interval is not likely to miss a curable prostate cancer when the initial PSA level is less than 2.0 ng/mL. Recognizing that 70% of a screened population between the ages of 50 years and 70 years have PSA levels less than 2.0 ng/mL, elimination of annual PSA testing for these men would result in large health care cost savings. C1 JOHNS HOPKINS UNIV,JOHNS HOPKINS HOSP,JAMES BUCHANAN BRADY UROL INST,SCH MED,DEPT PATHOL,BALTIMORE,MD 21287. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. MERCK RES LABS,DEPT EPIDEMIOL,BLUE BELL,PA. RP Carter, HB (reprint author), JOHNS HOPKINS UNIV,JOHNS HOPKINS HOSP,JAMES BUCHANAN BRADY UROL INST,SCH MED,DEPT UROL,BALTIMORE,MD 21287, USA. RI Fozard, James Leonard/B-3660-2009 NR 20 TC 123 Z9 126 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 MAY 14 PY 1997 VL 277 IS 18 BP 1456 EP 1460 DI 10.1001/jama.277.18.1456 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA WX852 UT WOS:A1997WX85200030 PM 9145718 ER PT J AU Manski, TJ Heffner, DK Glenn, GM Patronas, NJ Pikus, AT Katz, D Lebovics, R Sledjeski, K Choyke, PL Zbar, B Linehan, WM Oldfield, EH AF Manski, TJ Heffner, DK Glenn, GM Patronas, NJ Pikus, AT Katz, D Lebovics, R Sledjeski, K Choyke, PL Zbar, B Linehan, WM Oldfield, EH TI Endolymphatic sac tumors - A source of morbid hearing loss in von Hippel-Lindau disease SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MIDDLE-EAR; SUPPRESSOR GENE; TEMPORAL BONE; PAPILLARY CYSTADENOMA; ADENOCARCINOMA; ADENOMA; IDENTIFICATION; MUTATIONS; ORIGIN AB Objectives.-Isolated reports suggest a possible association of endolymphatic sac tumors (ELSTs), which are extremely rare in the general population, with von Hippel-Lindau disease (VHL). To determine if hearing loss and ELSTs are a component of VHL, we examined prevalence, clinical presentation, and natural history of hearing loss and ELSTs in VHL. Design.-Brain magnetic resonance images (MRIs) from 374 patients screened for VHL were reviewed for evidence of ELSTs. The VHL patients with MRI evidence suggestive of ELSTs or a history of hearing loss, tinnitus, or vertigo underwent additional radiologic and audiologic evaluations. To further assess prevalence of hearing loss and ELST in VHL, the next 66 patients screened in the VHL clinic (49 with proven VHL, 17 at risk for VHL) received MRI and audiologic assessment, Setting.-Referral center. Participants.-Study subjects comprised 374 persons screened for VHL, 66 consecutive patients with VHL or at risk for VHL, 4 patients with 6 ELSTs, and 13 previously reported patients with VHL and invasive tumors of the temporal bone. Intervention.-Magnetic resonance image and computed tomographic (CT) scan of the posterior fossa and audiologic assessment. Main Outcome Measures.-Any ELST visible on MRI or CT and hearing loss compatible with ELST. Results.-Magnetic resonance imaging revealed evidence of 15 ELSTs in 13 (11%) of 121 patients with VHL, but in none of the 253 patients without evidence of VHL (P<.001), Clinical findings in these 13 patients included hearing toss (13), tinnitus (12), vertigo (8), and facial paresis (1). Mean age al onset of hearing loss was 22 years (range, 12-50 years). Hearing for pure tones was abnormal in all affected ears and in 6 of the 11 additional, allegedly unaffected ears. In 8 patients (62%), hearing loss was the first manifestation of VHL. Presence or absence of hearing loss was associated with duration of symptoms (P<.002) and with tumor size (P<.01). Further, 43 (65%) of the 66 patients from the VHL clinic had pure tone threshold abnormalities, abnormalities that occurred bilaterally in 23 (54%) of the 43 affected subjects; however, evidence is lacking for a definitive association with ELST (3 [6%] of 49 patients with proven VHL had ELST evident on MRI). Conclusions.-Hearing loss and ELSTs are frequently associated with VHL syndrome and should be considered when screening individuals at risk for VHL and when monitoring patients with an established diagnosis of VHL. Many patients with VHL have hearing loss without radiographic evidence of an ELST. Whether it is caused by an ELST that is too small to be detected by MRI or is produced by some other etiology is still unknown. Audiologic evaluation and MRI should allow early detection and enhance management of hearing loss in these patients. C1 NINCDS, SURG NEUROL BRANCH, NIH, BETHESDA, MD 20892 USA. NATL NAVAL MED CTR, DEPT NEUROSURG, BETHESDA, MD 20889 USA. ARMED FORCES INST PATHOL, DEPT OTOLARYNG PATHOL, BETHESDA, MD USA. NCI, GENET EPIDEMIOL BRANCH, DIV CANC EPIDEMIOL & GENET, BETHESDA, MD 20892 USA. NIH, DEPT RADIOL, HENRY M JACKSON FDN, WARREN GRANT MAGNUSON CLIN CTR, BETHESDA, MD 20892 USA. NATL INST DEAFNESS & OTHER COMMUN DISORDERS, NEUROOTOL BRANCH, BETHESDA, MD USA. NINCDS, OFF CLIN DIRECTOR, BETHESDA, MD 20892 USA. NCI, PATHOL LAB, BETHESDA, MD 20892 USA. NCI, IMMUNOBIOL LAB, DIV CANC BIOL DIAG & CTR, FREDERICK CANC RES FACIL, BETHESDA, MD 20892 USA. NCI, UROL ONCOL BRANCH,CLIN ONCOL PROGRAM, DIV CANC THERAPY,NIH, BETHESDA, MD 20892 USA. NR 44 TC 147 Z9 152 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 14 PY 1997 VL 277 IS 18 BP 1461 EP 1466 DI 10.1001/jama.277.18.1461 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA WX852 UT WOS:A1997WX85200031 PM 9145719 ER PT J AU Geller, G Botkin, JR Green, MJ Press, N Biesecker, B Wilfond, B Grana, G Daly, MB Schneider, K Kahn, MJE AF Geller, G Botkin, JR Green, MJ Press, N Biesecker, B Wilfond, B Grana, G Daly, MB Schneider, K Kahn, MJE TI Genetic testing for susceptibility to adult-onset cancer - The process and content of informed consent SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID COMPUTER-ASSISTED-INSTRUCTION; LINE P53 MUTATIONS; OVARIAN-CANCER; PATIENT EDUCATION; BREAST-CANCER; HUNTINGTON DISEASE; COLON-CANCER; KNOWLEDGE; DISCRIMINATION; UNDERSTAND AB Objective.-To provide guidance on informed consent to clinicians offering cancer susceptibility testing. Participants.-The Task Force on Informed Consent is part of the Cancer Genetics Studies Consortium (CGSC), whose members were recipients of National Institutes of Health grants to assess the implications of cancer susceptibility testing. The 10 task force members represent a range of relevant backgrounds, including various medical specialties, social science, genetic counseling, and consumer advocacy. Evidence.-The CGSC held 3 public meetings from 1994 to 1996. At its first meeting, the task force jointly established a list of topics. The cochairs (G.G. and J.R.B) then developed an outline and assigned each topic to an appropriate writer and reviewer, Writers summarized the literature on their topics and drafted recommendations, which were then revised by the reviewers. The cochairs compiled and edited the entire manuscript. All members were involved in writing this report. Consensus Process.-The first draft was distributed to task force members, after which a meeting was held to discuss its content and organization. Consensus was reached by voting. A subsequent draft was presented to the entire CGSC at its third meeting, and comments were incorporated. Conclusions.-The task force recommends that informed consent for cancer susceptibility testing be an ongoing process of education and counseling in which (1) providers elicit participant, family, and community values and disclose their own, (2) decision making is shared, (3) the style of information disclosure is individualized, and (4) specific content areas are discussed. C1 UNIV UTAH,ECCLES INST HUMAN GENET,UTAH CTR HUMAN GENOME RES,SALT LAKE CITY,UT. MILTON S HERSHEY MED CTR,DEPT HUMANITIES,HERSHEY,PA. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. NATL HUMAN GENOME RES INST,MED GENET BRANCH,BETHESDA,MD. UNIV ARIZONA,DEPT PEDIAT,TUCSON,AZ 85721. CANC CTR SO NEW JERSEY,CAMDEN,NJ. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. DANA FARBER CANC INST,BOSTON,MA 02115. NATL BREAST CANC COALIT,RICHMOND,VA. RP Geller, G (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,550 N BROADWAY,SUITE 511,BALTIMORE,MD 21205, USA. NR 119 TC 143 Z9 145 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 14 PY 1997 VL 277 IS 18 BP 1467 EP 1474 DI 10.1001/jama.277.18.1467 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA WX852 UT WOS:A1997WX85200032 PM 9145720 ER PT J AU Shanmugam, V Chackalaparampil, I Kundu, GC Mukherjee, AB Mukherjee, BB AF Shanmugam, V Chackalaparampil, I Kundu, GC Mukherjee, AB Mukherjee, BB TI Altered sialylation of osteopontin prevents its receptor-mediated binding on the surface of oncogenically transformed tsB77 cells SO BIOCHEMISTRY LA English DT Article ID JB6 EPIDERMAL-CELLS; NEOPLASTIC TRANSFORMATION; BONE SIALOPROTEIN; RAT BONE; SECRETED PHOSPHOPROTEIN-1; MAMMALIAN-CELLS; TUMOR PROMOTER; IN-VITRO; ADHESION; TUMORIGENICITY AB It has been reported previously that oncogenically transformed cells secrete different molecular forms of osteopontin (OPN), a sialic acid-rich, adhesive, phosphoglycoprotein, than OPNs secreted by their nontransformed counterparts. However, the origin of the OPN isoform secreted by the transformed cells and whether it has different physiological properties which may serve transformation-specific functions remain poorly understood. Here, we report that Rat-1 cells transformed by a temperature-sensitive mutant of Rous sarcoma virus (tsB77) secrete two discrete molecular forms of OPN, a 69-kDa OPN at the nonpermissive temperature (41 degrees C) and a 62-kDa form at the permissive temperature (34 degrees C). However, tsB77 cells at both temperatures transcribe a single 1.6 kb OPN mRNA and contain only the 69-kDa form of OPN intracellularly, suggesting that the 69-kDa OPN is modified to the 62-kDa form prior to or immediately after secretion by cells at 34 degrees C. We ruled out proteolytic cleavage, differential phosphorylation, or lack of N- or O-linked carbohydrates as the possible mechanism, but found that the 62-kDa OPN contains significantly reduced levels of sialic acid, as compared to its 69-kDa form. The binding assays using P-32-labeled OPN revealed that only the 69-kDa OPN, not its 62-kDa form, undergoes receptor-mediated localization on the cell surface, although tsB77 cells synthesize OPN receptors (alpha(v) beta(3) integrins) at both permissive and nonpermissive temperatures. Furthermore, I-125-labeled purified milk OPN, which is highly sialylated and shows cell surface binding, upon digestion with neuraminidase failed to interact with the cell surface. Taken together, these results suggest that the difference between the 69-kDa and 62-kDa isoforms of OPN resides in their sialic acid content, and sialylation of OPN is crucial for its receptor-mediated binding on tsB77 cells. The data presented here demonstrate for the first time a physiological role of sialic acids in, this protein, and raise the possibility that oncogenically transformed tsB77 cells may exploit the lack of OPN-receptor interactions for their invasive behavior. C1 MCGILL UNIV,DEPT BIOL,MONTREAL,PQ H3A 1B1,CANADA. MCGILL UNIV,DEPT HUMAN GENET,MONTREAL,PQ H3A 1B1,CANADA. NICHHD,SECT DEV GENET,HERITABLE DISORDERS BRANCH,NIH,BETHESDA,MD 20892. NR 43 TC 36 Z9 37 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 MAY 13 PY 1997 VL 36 IS 19 BP 5729 EP 5738 DI 10.1021/bi961687w PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WY820 UT WOS:A1997WY82000014 PM 9153413 ER PT J AU Ghosh, M Williams, J Powell, MD Levin, JG LeGrice, SFJ AF Ghosh, M Williams, J Powell, MD Levin, JG LeGrice, SFJ TI Mutating a conserved motif of the HIV-1 reverse transcriptase palm subdomain alters primer utilization SO BIOCHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RNASE-H ACTIVITIES; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; THUMB SUBDOMAIN; RIBONUCLEASE H; TYPE-1; POLYMERASE; DNA; MUTAGENESIS AB In order to investigate how primer grip residues of human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) contribute toward the architecture of its palm subdomain and neighboring structural elements, the DNA polymerase and ribonuclease H (RNase H) activities of enzymes bearing aromatic substitutions at Trp(229) and Tyr(232) of the catalytically-competent p66 subunit were evaluated. Although all mutants retained RNase H function, the manner in which different RNA-DNA hybrids were hydrolyzed was affected. Depending on the nature of the substitution, DNA-dependent DNA synthesis was (i) unaffected, (ii) interrupted shortly after initiation, or (iii) stalled when the replication machinery encountered an intramolecular duplex on the single-stranded template. Evaluating (-) strand strong-stop DNA synthesis on an RNA template derived from the viral genome raises the additional possibility that DNA and RNA primers might be differentially recognized by the retroviral polymerase. In support of this, all mutants were unable to extend the HIV-1 polypurine tract (PPT) RNA primer into (+) strand DNA, despite supporting the equivalent event from an oligodeoxynucleotide primer. Collectively, our data illustrate that subtle alterations to primer grip architecture may manifest themselves in discrimination between oligoribo- and oligodeoxyribonucleic acid primers. C1 CASE WESTERN RESERVE UNIV,SCH MED,DIV INFECT DIS,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,SCH MED,CTR AIDS RES,CLEVELAND,OH 44106. NICHHD,MOL GENET LAB,NIH,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM 52263] NR 48 TC 52 Z9 52 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 13 PY 1997 VL 36 IS 19 BP 5758 EP 5768 DI 10.1021/bi963045e PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WY820 UT WOS:A1997WY82000017 PM 9153416 ER PT J AU Pak, M Wickner, S AF Pak, M Wickner, S TI Mechanism of protein remodeling by ClpA chaperone SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE protein folding; plasmid P1; ATP-dependent proteolysis; molecular chaperones ID HEAT-SHOCK PROTEINS; ESCHERICHIA-COLI; SPECIFICITY COMPONENT; MOLECULAR CHAPERONE; DNA-REPLICATION; ATP HYDROLYSIS; BINDING; RELEASE; HSP104; GROEL AB ClpA, a newly discovered ATP-dependent molecular chaperone, remodels bacteriophage P1 RepA dimers into monomers, thereby activating the latent specific DNA binding activity of RepA. We investigated the mechanism of the chaperone activity of ClpA by dissociating the reaction into several steps and determining the role of nucleotide in each step. In the presence of ATP or a nonhydrolyzable ATP analog, the initial step is the self-assembly of ClpA and its association with inactive RepA dimers. ClpA-RepA complexes form rapidly and at 0 degrees C but are relatively unstable. The next step is the conversion of unstable ClpA-RepA complexes into stable complexes in a lime and temperature-dependent reaction. The transition to stable ClpA-RepA complexes requires binding of ATP, but not ATP hydrolysis, because nonhydrolyzable ATP analogs satisfy the nucleotide requirement. The stable complexes contain approximately I mol of RepA dimer per mol of ClpA hexamer and are committed to activating RepA. In the last step of the reaction, active RepA is released upon exchange of ATP with the nonhydrolyzable ATP analog and ATP hydrolysis. Importantly, we discovered that one cycle of RepA binding to ClpA followed by ATP-dependent release is sufficient to convert inactive RepA to its active form. C1 NCI,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 28 TC 69 Z9 70 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 MAY 13 PY 1997 VL 94 IS 10 BP 4901 EP 4906 DI 10.1073/pnas.94.10.4901 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WZ257 UT WOS:A1997WZ25700017 PM 9144162 ER PT J AU Bossers, A Belt, PBGM Raymond, GJ Caughey, B deVries, R Smits, MA AF Bossers, A Belt, PBGM Raymond, GJ Caughey, B deVries, R Smits, MA TI Scrapie susceptibility-linked polymorphisms modulate the in vitro conversion of sheep prion protein to protease-resistant forms SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE allelic variants; protein conformation; spongiform encephalopathy; proteinase K resistant ID NATURAL SCRAPIE; PRP; GENE; ALLELES; DISEASE; CELLS; PROPAGATION; CODON-136; INFECTION; ISOLATE AB Prion diseases are natural transmissible neurodegenerative disorders in humans and animals. They are characterized by the accumulation of a protease-resistant scrapie-associated prion protein (PrPSc) of the host-encoded cellular prion protein (PrPC) mainly in the central nervous system. Polymorphisms in the PrP gene are linked to differences in susceptibility for prion diseases. The mechanisms underlying these effects are still unknown. Here we describe studies of the influence of sheep PrP polymorphisms on the conversion of PrPC into protease-resistant forms. In a cell-free system, sheep Prp(Sc) induced the conversion of sheep PrPC into protease-resistant PrP (PrP res) similar or identical to PrPSc. Polymorphisms present in either PrPC or PrPSc had dramatic effects on the cell-free conversion efficiencies. The PrP variant associated with a high susceptibility to scrapie and short survival times of scrapie-affected sheep was efficiently converted into PrP-res. The wild-type PrP variant associated with a neutral effect on susceptibility and intermediate survival times was converted with intermediate efficiency. The PrP variant associated with scrapie resistance and long survival times was poorly converted. Thus the in vitro conversion characteristics of the sheep PrP variants reflect their linkage with scrapie susceptibility and survival times of scrapie-affected sheep. The modulating effect of the polymorphisms in PrPC and PrPSc on the cell-free conversion characteristics suggests that, besides the species barrier, polymorphism barriers play a significant role in the transmissibility of prion diseases. C1 DLO,INST ANIM SCI & HLTH,DEPT BACTERIOL,NL-8200 AB LELYSTAD,NETHERLANDS. DLO,INST ANIM SCI & HLTH,DEPT PROD,NL-8200 AB LELYSTAD,NETHERLANDS. NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. RI smits, mari/J-4892-2013; OI smits, mari/0000-0002-3493-291X; Bossers, Alex/0000-0002-6586-717X NR 42 TC 136 Z9 138 U1 3 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 MAY 13 PY 1997 VL 94 IS 10 BP 4931 EP 4936 DI 10.1073/pnas.94.10.4931 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WZ257 UT WOS:A1997WZ25700022 PM 9144167 ER PT J AU Diehl, SR Erickson, RP AF Diehl, SR Erickson, RP TI Genome scan for teratogen-induced clefting susceptibility loci in the mouse: Evidence of both allelic and locus heterogeneity distinguishing cleft lip and cleft palate SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GROWTH-FACTOR-ALPHA; RECOMBINANT INBRED LINES; AUTOSOMAL MAJOR LOCUS; GENETIC-ANALYSIS; SEGREGATION ANALYSIS; MICE; ASSOCIATION; RECEPTOR; DOMINANT; DEFECTS AB Nonsyndromic clefting of the lip and palate in humans has a highly complex etiology, with both multiple genetic loci and exposure to teratogens influencing susceptibility. Previous studies using mouse models have examined only very small portions of the genome. Here we report the findings of a genome-wide search for susceptibility genes for teratogen-induced clefting in the AXE and BXA set of recombinant inbred mouse strains. We compare results obtained using phenytoin (which induces cleft lip) and 6-aminonicotinamide (which induces cleft palate). We use a new statistical approach based on logistic regression suitable for these categorical data to identify several chromosomal regions as possible locations of clefting susceptibility loci, and we review candidate genes located within each region. Because cleft lip and cleft palate do not frequently co-aggregate in human families and because these structures arise semi-independently during development, these disorders are usually considered to be distinct in etiology. Our data, however, implicate several of the same chromosomal regions for both forms of clefting when teratogen-induced. Furthermore, different parental strain alleles are usually associated with clefting of the lip versus that of the palate (i.e., allelic heterogeneity). Because several other chromosomal regions are associated with only one form of clefting, locus heterogeneity also appears to be involved. Our findings in this mouse model suggest several priority areas for evaluation in human epidemiological studies. C1 UNIV ARIZONA,HLTH SCI CTR,DEPT PEDIAT,TUCSON,AZ 85724. RP Diehl, SR (reprint author), NIDR,ORAL HLTH PROMOT RISK FACTORS & MOL EPIDEMIOL BRA,NIH,ROOM 4AS-49E,BLDG 45,BETHESDA,MD 20892, USA. FU NIDCR NIH HHS [Z01DE00633] NR 68 TC 35 Z9 35 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 13 PY 1997 VL 94 IS 10 BP 5231 EP 5236 DI 10.1073/pnas.94.10.5231 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WZ257 UT WOS:A1997WZ25700075 PM 9144220 ER PT J AU Shen, FS Loh, YP AF Shen, FS Loh, YP TI Intracellular misrouting and abnormal secretion of adrenocorticotropin and growth hormone in Cpe(fat) mice associated with a carboxypeptidase E mutation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE prohormone sorting; neuropeptides; pro-opiomelanocortin ID TRANS-GOLGI NETWORK; PROCESSING ENZYMES; SORTING SIGNAL; MESSENGER-RNA; PROOPIOMELANOCORTIN; IDENTIFICATION; PITUITARY; PATHWAY; PC2; PROHORMONE AB Cpe(fat) mice carry a mutation in the carboxypeptidase E/H gene which encodes an exopeptidase that removes C-terminal basic residues from endoproteolytically cleaved hormone intermediates. These mice have endocrine disorders including obesity, infertility, and hyperproinsulinemia-diabetes syndrome, but the etiology remains an enigma, Because studies have identified membrane carboxypeptidase E as a sorting receptor for targeting prohormones to the regulated secretory pathway for processing and secretion, the intracellular routing and secretion of pro-opiomelanocortin/adrenocorticotropin and growth hormone from anterior pituitary cells were investigated in Cpe(fat) mice. In Cpe(fat) mice, pro-opiomelanocortin was accumulated 24-fold above normal animals in the pituitary and it was poorly processed to adrenocorticotropin. Furthermore, pro-opiomelanocortin was secreted constitutively at high levels, showing no response to stimulation by corticotropin-releasing hormone. Similarly, growth hormone release was constitutive and did not respond to high K+ stimulation, Both pro-opiomelanocortin and growth hormone levels were elevated in the circulation of Cpe(fat) mice versus normal mice. These data provide evidence that the lack of carboxypeptidase E, the sorting receptor, results in the intracellular misrouting and secretion of pro-opiomelanocortin and growth hormone via the constitutive pathway in the pituitary of Cpe(fat) mice. C1 NICHHD,CELLULAR NEUROBIOL SECT,DEV NEUROBIOL LAB,NIH,BETHESDA,MD 20892. NR 33 TC 57 Z9 58 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 13 PY 1997 VL 94 IS 10 BP 5314 EP 5319 DI 10.1073/pnas.94.10.5314 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WZ257 UT WOS:A1997WZ25700089 PM 9144234 ER PT J AU Nielsen, S Terris, J Andersen, D Ecelbarger, C Frokiaer, J Jonassen, T Marples, D Knepper, MA Petersen, JS AF Nielsen, S Terris, J Andersen, D Ecelbarger, C Frokiaer, J Jonassen, T Marples, D Knepper, MA Petersen, JS TI Congestive heart failure in rats is associated with increased expression and targeting of aquaporin-2 water channel in collecting duct SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hyponatremia; water retention ID VASOPRESSIN; KIDNEY; CLONING; MEMBRANE; PLASMA; SODIUM; PERMEABILITY; EXCRETION; GLYCEROL; PROTEIN AB We tested whether severe congestive heart failure (CHF), a condition associated with excess free-water retention, is accompanied by altered regulation of the vasopressin-regulated water channel, aquaporin-2 (AQP2), in the renal collecting duct, CHF was induced by left coronary artery ligation, Compared with sham-operated animals, rats with CHF had severe heart failure with elevated left ventricular end-diastolic pressures (LVEDP): 26.9 +/- 3.4 vs, 4.1 +/- 0.3 mmHg, and reduced plasma sodium concentrations (142.2 +/- 1.6 vs, 149.1 +/- 1.1 mEq/liter). Quantitative immunoblotting of total kidney membrane fractions revealed a significant increase in AQP2 expression in animals with CHF (267 +/- 53%, n = 12) relative to sham-operated controls (100 +/- 13%, n = 14), In contrast, immunoblotting demonstrated a lack of an increase in expression of AQP1 and AQP3 water channel expression, indicating that the effect on AQP2 was selective, Furthermore, postinfarction animals without LVEDP elevation or plasma Na reduction showed no increase in AQP2 expression (121 +/- 28% of sham levels, n = 6), Immunocytochemistry and immunoelectron microscopy demonstrated very abundant labeling of the apical plasma membrane and relatively little labeling of intracellular vesicles in collecting duct cells from rats with severe CHF, consistent with enhanced trafficking of AQP2 to the apical plasma membrane, The selective increase in AQP2 expression and enhanced plasma membrane targeting provide an explanation for the development of water retention and hyponatremia in severe CHF. C1 UNIV AARHUS,INST EXPT CLIN RES,DK-8000 AARHUS C,DENMARK. UNIV AARHUS,INST ANAT,DEPT CELL BIOL,DK-8000 AARHUS C,DENMARK. UNIV COPENHAGEN,PANUM INST,DEPT PHARMACOL,DK-2200 COPENHAGEN,DENMARK. UNIV LEEDS,DEPT PHYSIOL,LEEDS LSZ 9NQ,W YORKSHIRE,ENGLAND. RP Nielsen, S (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,NIH,BLDG 9,ROOM 1N105,9 MEM DR,MSC 0951,BETHESDA,MD 20892, USA. NR 36 TC 148 Z9 154 U1 1 U2 5 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 MAY 13 PY 1997 VL 94 IS 10 BP 5450 EP 5455 DI 10.1073/pnas.94.10.5450 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WZ257 UT WOS:A1997WZ25700113 PM 9144258 ER PT J AU Pritchard, JB Miller, DS AF Pritchard, JB Miller, DS TI Renal secretion of organic cations: A multistep process SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE kidney; proximal tubule; membrane transport; drug excretion; proton-ATPase; endosome; membrane trafficking; multidrug resistance transporter (MDR); proton/organic cation exchange; facilitated diffusion ID BRUSH-BORDER MEMBRANE; CONTRALUMINAL TRANSPORT-SYSTEM; CARRIER-MEDIATED TRANSPORT; MULTIDRUG-RESISTANCE GENE; BOREALIS URINARY-BLADDER; RABBIT PROXIMAL TUBULE; P-GLYCOPROTEIN; BASOLATERAL MEMBRANE; RAT-KIDNEY; TETRAETHYLAMMONIUM TRANSPORT AB A wide variety of positively charged drugs and drug metabolites are very effectively excreted from the body via the renal organic cation transport system. Organic cation transport is a multistep process taking place in the proximal tubule, particularly in its initial, or S-1, segment. Transport from the blood into the tubular cell occurs by facilitated diffusion, driven by the electrochemical gradient for organic cations across the basolateral membrane. Upon entry, a substantial fraction of the cation (1/3 - 2/3) is actively transported into endosomal vesicles in exchange for intravesicular protons. A steep proton gradient is maintained between the vesicle's interior and the cytoplasm by a potent proton-ATPase. Sequestration may protect the cells by reducing the cytoplasmic content of potentially toxic agents during their excretion. Preliminary evidence also suggests that microtubule-dependent vesicular trafficking plays a direct role in transcellular flux of cationic drugs. At the luminal membrane, cationic drugs are transported into the tubular lumen via proton/organic cation antiport. In addition, larger, more lipophilic cations may be actively extruded via ATP-driven transport mediated by the multidrug resistance transporter. Together, the multiple steps of organic cation secretion control the excretory rate for cationic drugs and, thus, influence both residence time within the body and concentrations in plasma and at specific target sites. RP Pritchard, JB (reprint author), NIEHS,LAB PHARMACOL & CHEM,NIH,RES TRIANGLE PK,NC 27709, USA. NR 82 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD MAY 12 PY 1997 VL 25 IS 2-3 BP 231 EP 242 DI 10.1016/S0169-409X(97)00501-2 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XJ129 UT WOS:A1997XJ12900005 ER PT J AU Glaudemans, CPJ Miller, CE Nashed, EM AF Glaudemans, CPJ Miller, CE Nashed, EM TI The measurement of affinity between ligand and antibody using ligand-induced antibody fluorescence change SO CARBOHYDRATE RESEARCH LA English DT Article DE ligand-antibody affinity; protein fluorescence AB Computational analysis shows that affinity measurements using ligand-induced protein fluorescence change [Carbohydr. Res. 33 (1974) 377-382] give reliable data for K(a)s for values in the order of from ca. 10(2) M-1 to ca. 10(7) M-1. (C) 1997 Published by Elsevier Science Ltd. RP Glaudemans, CPJ (reprint author), NIDDK,NIH,BETHESDA,MD 20892, USA. NR 2 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD MAY 12 PY 1997 VL 300 IS 2 BP 169 EP 170 DI 10.1016/S0008-6215(97)00042-6 PG 2 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA XB923 UT WOS:A1997XB92300010 PM 9203342 ER PT J AU Quock, RM Hosohata, Y Knapp, RJ Burkey, TH Hosohata, K Zhang, XY Rice, KC Nagase, H Hruby, VJ Porreca, F Roeske, WR Yamamura, HI AF Quock, RM Hosohata, Y Knapp, RJ Burkey, TH Hosohata, K Zhang, XY Rice, KC Nagase, H Hruby, VJ Porreca, F Roeske, WR Yamamura, HI TI Relative efficacies of delta-opioid receptor agonists at the cloned human delta-opioid receptor SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE efficacy; delta-opioid receptor, human; radioligand binding; delta-opioid receptor agonist; [S-35]GTP gamma S binding ID RAT-BRAIN; INHIBITION; BINDING; SNC-80 AB The present study was conducted to determine the relative efficacies of the selective delta-opioid receptor agonists SNC80 ((+)-4-[(alpha R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide), pCl-DPDPE (cyclic[D-Pen(2),4'-CIPhe(4), D-Pen(5)]enkephalin) and (-)-TAN67 ((-)-2-methyl-4a alpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12a alpha-octahydro-quinolino-[2,3,3-g]isoquinoline). Experiments compared the abilities of the three drugs to competitively inhibit [H-3]naltrindole binding and also stimulate [S-35]GTP gamma S binding in membranes prepared from stably transfected Chinese hamster ovary (CHO) cells that express the cloned human delta-opioid receptor. Efficacy was determined according to the formula:efficacy=(Emax-A/E-max)(A'/A+1)x0.5. Results show that SNC80 and pCl-DPDPE had efficacy values that were about 6-7 times greater than that of(-)-TAN67. C1 UNIV ARIZONA,COLL MED,HLTH SCI CTR,DEPT PHARMACOL,TUCSON,AZ 85724. UNIV ARIZONA,DEPT BIOCHEM,TUCSON,AZ 85724. UNIV ARIZONA,DEPT PSYCHIAT,TUCSON,AZ 85724. UNIV ARIZONA,DEPT CHEM,TUCSON,AZ 85724. UNIV ARIZONA,PROGRAM NEUROSCI,TUCSON,AZ 85724. NIDDKD,MED CHEM LAB,NIH,BETHESDA,MD 20892. TORAY INDUSTRIES LTD,BASIC RES LAB,KAMAKURA,KANAGAWA 248,JAPAN. NR 13 TC 30 Z9 30 U1 0 U2 2 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 MAY 12 PY 1997 VL 326 IS 1 BP 101 EP 104 DI 10.1016/S0014-2999(97)83488-7 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WZ404 UT WOS:A1997WZ40400014 PM 9178661 ER PT J AU Adamson, RH AF Adamson, RH TI Sixth international conference on carcinogenic/mutagenic N-substituted aryl compounds: Conclusions and perspectives SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT 6th International Conference on Carcinogenic and Mutagenic N-Substituted Aryl Compounds CY NOV 04-08, 1995 CL MONTEREY, CA SP Flavor & Extract Manufacturers Assoc US, Int Flavors & Fragrances Inc, Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, US FDA, Natl Ctr Toxicol Res, NCI, NIEHS, Nestle S A, Toronto Res Chem Inc DE heterocyclic amine; carcinogenesis; risk assessment; risk communication ID 5 HETEROCYCLIC AMINES; RATS; MUTAGENS C1 NCI, DIV CANC ETIOL, BETHESDA, MD 20892 USA. NR 13 TC 3 Z9 3 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 MAY 12 PY 1997 VL 376 IS 1-2 BP 3 EP 6 DI 10.1016/S0027-5107(97)00018-3 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA XE489 UT WOS:A1997XE48900002 ER PT J AU MacLeod, S Sinha, R Kadlubar, FF Lang, NP AF MacLeod, S Sinha, R Kadlubar, FF Lang, NP TI Polymorphisms of CYP1A1 and GSTM1 influence the in vivo function of CYP1A2 SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT 6th International Conference on Carcinogenic and Mutagenic N-Substituted Aryl Compounds CY NOV 04-08, 1995 CL MONTEREY, CA SP Flavor & Extract Manufacturers Assoc US, Int Flavors & Fragrances Inc, Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, US FDA, Natl Ctr Toxicol Res, NCI, NIEHS, Nestle S A, Toronto Res Chem Inc DE cytochrome P4501A1; cytochrome P4501A2; glutathione S-transferase M1; polymorphism ID CAFFEINE URINARY METABOLITES; HETEROCYCLIC AROMATIC-AMINES; CARCINOGEN-METABOLISM; CYTOCHROME P4501A2; N-ACETYLTRANSFERASE; GENE DELETION; HUMAN-LIVER; SUSCEPTIBILITY; PHENOTYPE; GENOTYPE AB Differences in human cancer susceptibility have been attributed to polymorphisms of carcinogen metabolizing enzymes. Our efforts have focused on the systems responsible for metabolism of aromatic and heterocyclic amines found in cigarette smoke and in cooked foods. Cytochrome P4501A2 (CYP1A2), which catalyzes aromatic and heterocyclic amine N-oxidation, has been implicated as a risk factor in both urinary bladder and colorectal cancer. In the present study we used the results of caffeine phenotyping experiments to measure the effects of cigarette smoke and compounds present in meat cooked at high temperature on CYP1A2 activity. Subjects in the smoking cessation study had mean CYP1A2 activity of 17.8 (expressed as the urinary molar ratio of [17X + 17U]/137X) while smoking; however, this activity decreased to 10.9 three weeks after cessation of smoking. Subjects in the cooked meat feeding study had mean CYP1A2 activity of 9.01 after 1 week of consuming meat cooked at low temperature, but this value increased to 12.7 after I week of consuming meat cooked at high temperature. Because no association has been identified between differences in CYP1A2 activity and variations in the CYP1A2 structural gene, we sought to determine whether the activities of other carcinogen metabolizing enzymes are involved in the regulation of CYP1A2 activity. CYP1A2 activity was higher in individuals who express the GSTM1 null allele compared to those expressing the GSTM1*A,B allele, 10.2 vs. 8.5 for unexposed conditions and 15.0 vs. 12.3 for exposed conditions. CYP1A1 genotyping demonstrated that individuals possessing the Ile/Ile CYP1A1 genotype had greater mean CYP1A2 activity than those who had the heterozygous Ile/Val allelic variant of the CYP1A1 gene. However, upon exposure to cigarette smoke or high-temperature cooked meat, individuals possessing the heterozygous form of the CYP1A1 gene had significantly increased CYP1A2 activity (18.1) compared to those with the more common Ile/Ile CYP1A1 genotype (13.3). These results indicate that CYP1A2, CYP1A1, and GSTM1 gene-gene interactions could be important confounders in the interpretation of molecular epidemiology studies. C1 JOHN L MCCLELLAN MEM VET ADM MED CTR,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,LITTLE ROCK,AR 72205. NCI,NIH,BETHESDA,MD 20892. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU NCI NIH HHS [R01 CA55751-03] NR 27 TC 48 Z9 49 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAY 12 PY 1997 VL 376 IS 1-2 BP 135 EP 142 DI 10.1016/S0027-5107(97)00036-5 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA XE489 UT WOS:A1997XE48900020 PM 9202749 ER PT J AU Poirier, MC Beland, FA AF Poirier, MC Beland, FA TI Aromatic amine DNA adduct formation in chronically-exposed mice: Considerations for human comparison SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT 6th International Conference on Carcinogenic and Mutagenic N-Substituted Aryl Compounds CY NOV 04-08, 1995 CL MONTEREY, CA SP Flavor & Extract Manufacturers Assoc US, Int Flavors & Fragrances Inc, Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, US FDA, Natl Ctr Toxicol Res, NCI, NIEHS, Nestle S A, Toronto Res Chem Inc DE 4-aminobiphenyl; cancer; lifetime exposure; bladder; Mouse ID CHRONIC CARCINOGEN EXPOSURE; HUMAN URINARY-BLADDER; TUMOR-INCIDENCE; CANCER RISK; 2-ACETYLAMINOFLUORENE; 4-AMINOBIPHENYL; SMOKING; EXAMPLE; TOBACCO; MODELS AB Lifetime chronic exposure of mice to the aromatic amines 4-aminobiphenyl (ABP) and 2-acetylaminofluorene (AAF) produces liver and urinary bladder tumors. In parallel experiments, DNA adduct levels in target tissues reach a steady-state (a balance between adduct formation and removal) after about four weeks of either AAF or ABP ingestion. For these and other carcinogens, steady-state DNA adduct levels most frequently increase linearly with dose, but the formation of tumors also depends upon a variety of factors, including the proliferative capacity of the target tissue, the sex of the animal, genotoxic properties of the specific adducts formed, and other unknown events. Chronic dosing experiments in animal models are of interest for human risk assessment because human exposure is typically intermittent, involving repeated exposures. However, it is to be expected that in a genetically-diverse human population, where the lifetime averages > 70 years, the relationship between tumorigenesis and DNA adduct formation will be relatively more complex than that observed in mice. From our studies of chronic ABP exposure in male mice, we have obtained the daily dose of ABP and the steady-state level of N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP) adduct associated with a 50% mouse bladder tumor incidence. Our attempt at a human extrapolation for adducts and urinary bladder cancer in smoking males (20-40 cigarettes/day) is based on the ABP dose per cigarette, values for the dG-C8-ABP adduct in bladder biopsies of lifetime heavy smokers at age similar to 70, and the smoking-related bladder tumor incidence (absolute lifetime risk) for Caucasian males in the United States aged 65-84 years. The extrapolation has produced two major predictions, one related to adduct formation and the other related to tumorigenesis. First, the observed level of smoking-related dG-C8-ABP in DNA of human bladder epithelium, expressed as a function of daily ABP intake, is about 3500-times higher than similar data for mice, which suggests that humans may perform the biotransformation of ABP more efficiently than mice. Second, at a similar bladder tumor incidence, mouse bladder contained adduct concentrations that were much higher than those observed in human bladder; for example, at a 2.6% tumor incidence, mouse bladder contained an average of 55.5 fmol dG-C8-ABP/mu g DNA (1850 adducts/10(8) nucleotides), while bladders from Caucasian male smokers contained an average of 0.036 fmol dG-C8-ABP/mu g DNA (1.2 adducts/10(8) nucleotides). This suggests that factors other than ABP-DNA adducts, such as adducts of other carcinogens, the influence of promoters, and synergistic effects of all of these factors contribute substantially to smoking-related bladder cancer in humans. C1 NATL CTR TOXICOL RES,JEFFERSON,AR 72079. RP Poirier, MC (reprint author), NCI,NIH,BLDG 37,RM 3B25,MSC-4253,37 CONVENT DR,BETHESDA,MD 20892, USA. NR 21 TC 8 Z9 9 U1 0 U2 1 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 MAY 12 PY 1997 VL 376 IS 1-2 BP 177 EP 184 DI 10.1016/S0027-5107(97)00041-9 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA XE489 UT WOS:A1997XE48900025 PM 9202754 ER PT J AU Sinha, R Rothman, N AF Sinha, R Rothman, N TI Exposure assessment of heterocyclic amines (HCAs) in epidemiologic studies SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT 6th International Conference on Carcinogenic and Mutagenic N-Substituted Aryl Compounds CY NOV 04-08, 1995 CL MONTEREY, CA SP Flavor & Extract Manufacturers Assoc US, Int Flavors & Fragrances Inc, Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, US FDA, Natl Ctr Toxicol Res, NCI, NIEHS, Nestle S A, Toronto Res Chem Inc DE heterocyclic amine; epidemiology; cancer; meat; cooking; genetic susceptibility; questionnaire; biomarker ID AROMATIC-AMINES; FOOD MUTAGENS; COOKED FOODS; FRIED MEAT; DIETARY; HUMANS; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE; CARCINOGENS; CANCER; RISK AB The carcinogenic potential of heterocyclic amines (HCAs) in humans has yet to be established Epidemiologic studies of colon cancer using crude surrogates for HCAs exposure (e.g., doneness of meat) have produced inconsistent results. To improve exposure assessment of HCAs, we have developed a database of HCA concentrations in commonly consumed meat items cooked by various techniques and degrees of doneness. HCA type and level are dependent on multiple factors, including type of meat (e.g., steak, chicken, bacon), cooking technique (with substantial variability present even within high temperature cooking methods), place of preparation (e.g., home, restaurant, or 'fast-food' restaurant), as well as the degree of doneness and surface browning/charring. We have developed a questionnaire with meat photographs linked to this database, which we are using in a variety of case-control and cohort studies of cancer etiology. In addition, we have carried out a metabolic study of HCA exposure among 66 subjects to identify biomarkers of HCA exposure which may be useful in epidemiologic studies. These studies should help clarify the role of HCAs in human carcinogenesis, and eventually allow an estimation of the cancer burden in the population attributable to these compounds. RP Sinha, R (reprint author), NCI, DIV CANC EPIDEMIOL & GENET, RM 430, 6130 EXECUT BLVD, EPN, BETHESDA, MD 20892 USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 34 TC 64 Z9 65 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAY 12 PY 1997 VL 376 IS 1-2 BP 195 EP 202 DI 10.1016/S0027-5107(97)00043-2 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA XE489 UT WOS:A1997XE48900027 PM 9202756 ER PT J AU Snyderwine, EG Turesky, RJ Turteltaub, KW Davis, CD Sadrieh, N Schut, HAJ Nagao, M Sugimura, T Thorgeirsson, UP Adamson, RH Thorgeirsson, SS AF Snyderwine, EG Turesky, RJ Turteltaub, KW Davis, CD Sadrieh, N Schut, HAJ Nagao, M Sugimura, T Thorgeirsson, UP Adamson, RH Thorgeirsson, SS TI Metabolism of food-derived heterocyclic amines in nonhuman primates SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT 6th International Conference on Carcinogenic and Mutagenic N-Substituted Aryl Compounds CY NOV 04-08, 1995 CL MONTEREY, CA SP Flavor & Extract Manufacturers Assoc US, Int Flavors & Fragrances Inc, Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, US FDA, Natl Ctr Toxicol Res, NCI, NIEHS, Nestle S A, Toronto Res Chem Inc DE metabolism; IQ; MeIQx; PhIP; food carcinogen; DNA adducts ID DNA ADDUCT LEVELS; CYNOMOLGUS MONKEYS; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; 2-AMINO-3,8-DIMETHYLIMIDAZO<4,5-F>QUINOXALINE MEIQX; MUTAGEN 2-AMINO-3-METHYLIMIDAZO<4,5-F>QUINOLINE; COOKED FOODS; ACTIVATION; IQ; CARCINOGEN; MICROSOMES AB During the cooking of meats, several highly mutagenic heterocyclic amines (HCAs) are produced. Three HCAs, IQ, MeIQx, and PhIP have been under study for carcinogenicity in cynomolgus monkeys, and to date, IQ has been shown to be a potent hepatocarcinogen. Concomitantly, the metabolic processing of these HCAs has been examined. Metabolism studies show that the potent hepatocarcinogenicity of IQ is associated with the in vivo metabolic activation of IQ via N-hydroxylation and the formation of DNA adducts. In monkeys undergoing carcinogen bioassay with IQ, N-hydroxylation was confirmed by the presence of the N-hydroxy-N-glucuronide conjugate of IQ in urine. The N-hydroxylation of IQ appears to be carried out largely by hepatic CYP3A4 and/or CYP2C9/10, and not by CYP1A2, an isoform not expressed in liver of this species. Notably MeIQx is poorly activated in cynomolgus monkeys and lacks the potency of IQ to induce hepatocellular carcinoma after a 5-year dosing period. The poor activation of MeIQx appears to be due to the lack of constitutive expression of CYP1A2 and an inability of other cytochromes P450, such as CYP3A4 and CYP2C9/10, to N-hydroxylate the quinoxalines. MeIQx is detoxified in monkeys largely by conjugation with glucuronide at the N-1 position, Although the carcinogenicity of PhIP is not yet known, the metabolic data suggest that PhIP will be carcinogenic in this species. PhIP is metabolically activated in vivo in monkeys by N-hydroxylation, as discerned by the presence of the N-hydroxy-N-glucuronide conjugate in urine, bile, and plasma. PhIP also produces DNA adducts that are widely distributed in tissues. The results from these studies support the importance of N-hydroxylation in the carcinogenicity of HCAs in nonhuman primates and by analogy, the importance of this metabolic activation step in the possible carcinogenicity of dietary HCAs in humans. C1 NESTEC LTD, NESTLE RES CTR, CH-1000 LAUSANNE, SWITZERLAND. LAWRENCE LIVERMORE NATL LAB, LIVERMORE, CA USA. MED COLL OHIO, DEPT PATHOL, TOLEDO, OH 43699 USA. NATL CANC CTR, RES INST, TOKYO 104, JAPAN. NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, BETHESDA, MD 20892 USA. NATL SOFT DRINK ASSOC, WASHINGTON, DC USA. RP Snyderwine, EG (reprint author), NCI, EXPT CARCINOGENESIS LAB, BLDG 37, ROOM 3C28, BETHESDA, MD 20892 USA. FU NCI NIH HHS [N01-CP-51013] NR 28 TC 41 Z9 46 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 EI 1873-135X J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAY 12 PY 1997 VL 376 IS 1-2 BP 203 EP 210 DI 10.1016/S0027-5107(97)00044-4 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA XE489 UT WOS:A1997XE48900028 PM 9202757 ER PT J AU Thorgeirsson, SS SantoniRugiu, E AF Thorgeirsson, SS SantoniRugiu, E TI Interaction of c-myc with transforming growth factor alpha and hepatocyte growth factor in hepatocarcinogenesis SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT 6th International Conference on Carcinogenic and Mutagenic N-Substituted Aryl Compounds CY NOV 04-08, 1995 CL MONTEREY, CA SP Flavor & Extract Manufacturers Assoc US, Int Flavors & Fragrances Inc, Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, US FDA, Natl Ctr Toxicol Res, NCI, NIEHS, Nestle S A, Toronto Res Chem Inc DE transgenic mouse; oncogene; suppressor gene; carcinogenesis ID MET PROTOONCOGENE PRODUCT; HEPATOCELLULAR-CARCINOMA CELLS; TUMOR CYTOTOXIC FACTOR; FACTOR SCATTER FACTOR; DNA ADDUCT FORMATION; PROTEIN-KINASE-C; TRANSGENIC MICE; EPITHELIAL-CELLS; HEPATIC DIFFERENTIATION; FACTOR/SCATTER FACTOR AB Double transgenic mice bearing fusion genes consisting of mouse albumin enhancer/promoter-mouse c-myc cDNA and mouse metallothionein 1 promoter-human TGF-alpha cDNA were generated to investigate the interaction of these genes in hepatic oncogenesis and to provide a general paradigm for characterizing the interaction of nuclear oncogenes and growth factors in tumorigenesis. Coexpression of c-myc and TGF-alpha as transgenes in the mouse liver resulted in a tremendous acceleration of neoplastic development in this organ as compared to expression of either of these transgenes alone. The two distinct cellular reactions that occurred in the liver of the double transgenic mice prior to the appearance of liver tumors were dysplastic and apoptotic changes in the existing hepatocytes followed by emergence of multiple focal lesions composed of both hyperplastic and dysplastic cell populations. These observations suggest that the interaction of c-myc and TGF-alpha, during development of hepatic neoplasia contributes to the selection and expansion of the preneoplastic cell populations which consequently increases the probability of malignant conversion. These studies have now been extended to examine the interaction of hepatocyte growth factor (HGF) with c-myc during hepatocarcinogenesis in the transgenic mouse model. While sustained overexpression of c-myc in the liver leads to cancer, coexpression of HGF and c-myc in the Liver delayed the appearance of preneoplastic lesions and prevented malignant conversion. Similarly, tumor promotion by phenobarbital was completely inhibited in the c-myc/HGF double transgenic mice whereas phenobarbital was an effective tumor promoter in the c-myc single transgenic mice. The results indicate that HGF may function as a tumor suppressor during early stages of Liver carcinogenesis, and suggest the possibility of therapeutic application for this cytokine. Furthermore, we show for the first time that interaction of c-myc with HGF or TGF-alpha results in profoundly different outcomes of the neoplastic process in the liver. RP Thorgeirsson, SS (reprint author), NCI,EXPT CARCINOGENESIS LAB,DIV BASIC SCI,NIH,BLDG 37,ROOM 3C28,37 CONVENT DR MSC4255,BETHESDA,MD 20892, USA. NR 91 TC 7 Z9 9 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 MAY 12 PY 1997 VL 376 IS 1-2 BP 221 EP 234 DI 10.1016/S0027-5107(97)00047-X PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA XE489 UT WOS:A1997XE48900030 PM 9202759 ER PT J AU Turesky, RJ Box, RM Markovic, J Gremaud, E Snyderwine, EG AF Turesky, RJ Box, RM Markovic, J Gremaud, E Snyderwine, EG TI Formation and persistence of DNA adducts of 2-amino-3-methylimidazo[4,5-f]quinoline in the rat and nonhuman primates SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT 6th International Conference on Carcinogenic and Mutagenic N-Substituted Aryl Compounds CY NOV 04-08, 1995 CL MONTEREY, CA SP Flavor & Extract Manufacturers Assoc US, Int Flavors & Fragrances Inc, Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, US FDA, Natl Ctr Toxicol Res, NCI, NIEHS, Nestle S A, Toronto Res Chem Inc DE food carcinogen; DNA adduct formation; adduct persistence and removal ID N-2 ATOMS; INDUCTION; CONFORMATION; GUANINE; C-8 AB The formation and persistence of the two principal DNA adducts of the food derived carcinogen 1-amino-3-methylimidazo[4,5-f]quinoline (IQ) have been investigated in rats and nonhuman primates. DNA adduct formation in the liver of male Fischer-344 rats occurred in a dose-dependent manner (0.01-20 mg/kg) where N-(deoxyguanosin-8-yl)-2-amino-3-methylimidazo[4,5-f]quinoline (dG-C8-IQ) and 5-(deoxyguanosin-N-2-yl)-2-amino-3-methylimidazo (dG-N-2-IQ) accounted for approximately 60-80% and 20-40%, respectively, of the total adducts observed by P-32 postlabeling. Similar DNA adduct profiles were observed in kidney and colorectal tissue of rats given a single oral dose of IQ (20 mg/kg) which, when given chronically to this species, results in tumorigenesis in liver and colorectum, but not in kidney. dG-C8-IQ was removed more rapidly than dG-N-2-IQ from liver and kidney, but removal of both adducts from the colorectum closely followed cell replication. Similar DNA adduct profiles were observed in liver and extrahepatic tissues of nonhuman primates following a single dose of IQ (20 mg/kg). In chronically treated monkeys undergoing carcinogen bioassay, there was a sharp increase in the contribution of dG-N-2-IQ to total DNA adducts in all slowly dividing tissues. There was no preferential accumulation of dG-N-2-IQ in the colon, a tissue with a high rate of cell division, and dG-C8-IQ remained the predominant lesion. These findings point to a preferential removal of the dG-C8-IQ adduct by enzyme repair system(s) in slowly dividing tissues in both rats and nonhuman primates. C1 NCI, EXPT CARCINOGENESIS LAB, DIV BASIC SCI, BETHESDA, MD 20892 USA. RP Turesky, RJ (reprint author), NESTEC LTD, NESTLE RES CTR, VERS CHEZ LES BLANC, CH-1000 LAUSANNE 26, SWITZERLAND. NR 20 TC 24 Z9 24 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 EI 1873-135X J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAY 12 PY 1997 VL 376 IS 1-2 BP 235 EP 241 DI 10.1016/S0027-5107(97)00048-1 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA XE489 UT WOS:A1997XE48900031 PM 9202760 ER PT J AU Goodarzi, G Chiu, R Brackmann, K Kohn, K Pommier, Y Grandgenett, DP AF Goodarzi, G Chiu, R Brackmann, K Kohn, K Pommier, Y Grandgenett, DP TI Host site selection for concerted integration by human immunodeficiency virus type-1 virions in vitro SO VIROLOGY LA English DT Article ID RETROVIRAL DNA INVITRO; HIV-1 INTEGRASE; IN-VITRO; DOMAINS; PROTEIN AB Host site selection for full-site integration by human immunodeficiency virus type-1 (HIV-1) integrase (IN) from nonionic detergent-lysed virions was investigated. Linear retrovirus-like DNA (469 bp) possessing 3' OH recessed long terminal repeal termini was efficiently inserted by a bimolecular donor reaction into a supercoiled DNA target (2867 bp), producing the HlV-1 5-bp host site duplication. Sequence data were analyzed from 193 donor-target recombinants obtained from the linear 3.8-kb DNA product. The selection of host target sites appeared randomly distributed and was independent of lysis and assay conditions. The fidelity of the 5-bp duplications in comparison to other size duplications was highest (94%) with high-salt (300 mM NaCl) lysis of the virions and 60 mM NaCl for strand transfer using Mg2+ as the divalent cation. Base sequence analysis demonstrated some biases in the 5-bp duplications at the sites of strand transfer and at the immediate host sequences surrounding the duplications. In addition to the observed duplications, similar to 30% of the recombinants isolated from the linear 3.8-kb DNA product contained specific and repetitive small-size deletions. No deletions smaller that 17 bp were observed and the distance between the deletion sets had a periodicity of similar to 10 bp. The mechanisms involved in how HIV-1 IN produces the 5-bp duplications and the repetitive host site deletions are discussed. (C) 1997 academic Press. C1 ST LOUIS UNIV,HLTH SCI CTR,INST MOL VIROL,ST LOUIS,MO 63110. GENET SYST INC,REDMOND,WA 98052. NCI,MOL PHARMACOL LAB,DIV BASIC SCI,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-31334] NR 31 TC 18 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 0042-6822 J9 VIROLOGY JI Virology PD MAY 12 PY 1997 VL 231 IS 2 BP 210 EP 217 DI 10.1006/viro.1997.8558 PG 8 WC Virology SC Virology GA XA091 UT WOS:A1997XA09100005 PM 9168883 ER PT J AU Skjaerven, R Wilcox, AJ Oyen, N Magnus, P AF Skjaerven, R Wilcox, AJ Oyen, N Magnus, P TI Mothers' birth weight and survival of their offspring: Population based study SO BRITISH MEDICAL JOURNAL LA English DT Article ID GESTATIONAL-AGE; PERINATAL-MORTALITY; GENERATIONS; GROWTH AB Objective: To test the hypothesis that a baby's survival is related to the mother's birth weight. Design: Population based dataset for two generations. Setting: Population registry in Norway. Subjects: All birth records for women born in Norway since 1967 were linked to births during 1981-94, thereby forming 105 104 mother-offspring units. Main outcome measures: Perinatal mortality specific for weight for offspring in groups of maternal birth weight (with 500 g categories in both). Results: A mother's birth weight was strongly associated with the weight of her baby. Maternal birth weight was associated with perinatal survival of her baby only for mothers with birth weights under 2000 g. These mothers were more likely to lose a baby in the perinatal period (odds ratio 2.3, 95% confidence interval 1.4 to 3.7). Among mothers with a birth weight over 2000 g there was no overall association between mother's weight and infant survival. There was, however, a strong interaction between mother's birth weight, infant birth weight, and infant survival. Mortality among small babies was much higher for those whose mothers had been large at birth. For example, babies weighing 2500-2999 g had a threefold higher mortality if their mother's birth weight had been high (greater than or equal to 4000 g) than if the mother had been small (2500-2999 g). Conclusion: Mothers who weighed less than 2000 g at birth have a higher risk of losing their own babies. For mothers who weighed greater than or equal to 2000 g their birth weight provides a benchmark for judging the growth of their offspring. Babies who are small relative to their mother's birth weight are at increased risk of mortality. C1 NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. UNIV BERGEN,DEPT PUBL HLTH & PRIMARY HLTH CARE,N-5021 BERGEN,NORWAY. NATL INST PUBL HLTH,DEPT EPIDEMIOL,N-0403 OSLO,NORWAY. RP Skjaerven, R (reprint author), UNIV BERGEN,MED INFORMAT & STAT SECT,ARMAUER HANSENS BLDG,N-5021 BERGEN,NORWAY. OI Wilcox, Allen/0000-0002-3376-1311 NR 25 TC 49 Z9 49 U1 0 U2 1 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 MAY 10 PY 1997 VL 314 IS 7091 BP 1376 EP 1380 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA WZ169 UT WOS:A1997WZ16900023 PM 9161309 ER PT J AU Goedert, JJ Kedes, DH Ganem, D AF Goedert, JJ Kedes, DH Ganem, D TI Antibodies to human herpesvirus 8 in women and infants born in Haiti and the USA SO LANCET LA English DT Article C1 UNIV CALIF SAN FRANCISCO,HOWARD HUGHES MED INST,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT MICROBIOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA. RP Goedert, JJ (reprint author), NCI,VIRAL EPIDEMIOL BRANCH,ROCKVILLE,MD 20852, USA. NR 4 TC 36 Z9 40 U1 1 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD MAY 10 PY 1997 VL 349 IS 9062 BP 1368 EP 1368 DI 10.1016/S0140-6736(05)63204-7 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA WY342 UT WOS:A1997WY34200017 PM 9149705 ER PT J AU Soliman, MS Cunningham, ML Morrow, JD Roberts, J Badr, MZ AF Soliman, MS Cunningham, ML Morrow, JD Roberts, J Badr, MZ TI Evidence against peroxisome proliferation-induced hepatic oxidative damage - Levels of esterified isoprostanes in livers of mice fed a diet containing [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (WY-14,643) SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE peroxisome proliferation; isoprostanes; oxidative damage; hepatocarcinogenesis; lipid peroxidation ID SHORT-TERM EXPOSURE; LIPID-PEROXIDATION; CLOFIBRIC ACID; RAT-LIVER; PERFLUORODECANOIC ACID; PERFLUOROOCTANOIC ACID; SIGNIFICANT INCREASE; HYPOLIPIDEMIC DRUGS; SELENIUM-DEFICIENT; ENZYME-ACTIVITIES AB It has been proposed that nongenotoxic peroxisome proliferators may cause hepatocellular cancer by an oxidative damage mediated mechanism(s). The argument for this hypothesis is based mainly on the noted ability of peroxisome proliferators to induce significantly H2O2-producing peroxisomal beta-oxidation while causing a minimal induction of H2O2-degrading catalase. The recent discovery, accurate determination, and use of isoprostanes as a sensitive indicator of oxidative damage prompted us to investigate whether induction of hepatic peroxisomal beta-oxidation in male B6C3F1 mice is accompanied by elevated levels of isoprostanes in those livers. The data show that while 7 days of feeding mice a diet containing 100 ppm [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (WY-14,643) increased peroxisomal beta-oxidation by 16-fold and catalase activity by only 2-fold, hepatic levels of esterified F-2-isoprostanes were not altered. These levels were 2.8 +/- 0.5 ng/g liver in control mice and 2.4 +/- 0.1 ng/g liver in mice fed the experimental diet for 7 days. Consequently, it is concluded that oxidative stress does not appear to occur in response to peroxisome proliferation, as evidenced by the lack of increase in hepatic levers of F-2-isoprostanes in livers of mice treated with the potent peroxisome proliferator WY-14,643. (C) 1997 Elsevier Science Inc. C1 UNIV MISSOURI,DIV PHARMACOL,KANSAS CITY,MO 64108. NIEHS,CHEM BRANCH,RES TRIANGLE PK,NC 27709. VANDERBILT UNIV,DEPT PHARMACOL,NASHVILLE,TN 37232. VANDERBILT UNIV,DEPT MED,NASHVILLE,TN 37232. OI soliman, Mahmoud/0000-0003-1948-7464 FU NIGMS NIH HHS [GM 42056] NR 42 TC 18 Z9 18 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 MAY 9 PY 1997 VL 53 IS 9 BP 1369 EP 1374 DI 10.1016/S0006-2952(97)87956-7 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XG543 UT WOS:A1997XG54300018 PM 9214698 ER PT J AU Wu, S Chen, WN Murphy, E Gabel, S Tomer, KB Foley, J Steenbergen, C Falck, JR Moomaw, CR Zeldin, DC AF Wu, S Chen, WN Murphy, E Gabel, S Tomer, KB Foley, J Steenbergen, C Falck, JR Moomaw, CR Zeldin, DC TI Molecular cloning, expression, and functional significance of a cytochrome P450 highly expressed in rat heart myocytes. SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ARACHIDONIC-ACID EPOXYGENASE; EPOXYEICOSATRIENOIC ACIDS; MICROSOMAL CYTOCHROME-P-450; ENANTIOFACIAL SELECTIVITY; STENOTOMUS-CHRYSOPS; SMOOTH-MUSCLE; HUMAN LIVER; K+-CHANNEL; METABOLITES; LOCALIZATION AB A cDNA encoding a P450 monooxygenase was amplified from reverse transcribed rat heart and liver total RNA by polymerase chain reaction using primers based on the 5'- and 3'-end sequences of two rat pseudogenes, CYP2J3P1 and CYP2J3P2. Sequence analysis revealed that this 1,778-base pair cDNA contained an open reading frame and encoded a new 502 amino acid protein designated CYP2J3. Based on the deduced amino acid sequence, CYP2J3 was approximately 70% homologous to both human CYP2J2 and rabbit CYP2J1. Recombinant CYP2J3 protein was co expressed with NADPH-cytochrome P450 oxidoreductase in Sf9 insect cells using a baculovirus expression system. Microsomal fractions of CYP2J3/NADPH-cytochrome P450 oxidoreductase-transfected cells metabolized arachidonic acid to 14,15-, 11,12-, and 8,9-epoxyeicosatrienoic acids and 19-hydroxyeicosatetraenoic acid as the principal reaction products (catalytic turnover, 0.2 nmol of product/nmol of cytochrome P450/min at 37 degrees C). Immunoblotting of microsomal fractions prepared from rat tissues using a polyclonal antibody raised against recombinant CYP2J2 that cross-reacted with CYP2J3 but not with other known rat P450s demonstrated abundant expression of CYP2J3 protein in heart and liver, Immunohistochemical staining of formalin-fixed paraffin-embedded rat heart tissue sections using the anti-CYP2J2 IgG and avidin-biotin-peroxidase detection localized expression of CYP2J3 primarily to atrial and ventricular myocytes, In an isolated-perfused rat heart model, 20 min of global ischemia followed by 40 min of reflow resulted in recovery of only 44 +/- 6% of base-line contractile function, The addition of 5 mu M 11,12-epoxyeicosatrienoic acid to the perfusate prior to global ischemia resulted in a significant 1.6 fold improvement in recovery of cardiac contractility (69 +/- 5% of base line, p = 0.01 versus vehicle alone). Importantly, neither 14,15-epoxyeicosatrienoic acid nor 19-hydroxyeicosatetraenoic acid significantly improved functional recovery following global ischemia, demonstrating the specificity of the biological effect for the 11,12-epoxyeicosatrienoic acid regioisomer. Based on these data, we conclude that (a) CYP2J3 is one of the predominant enzymes responsible for the oxidation of endogenous arachidonic acid pools in rat heart myocytes and (b) 11,12-epoxyeicosatrienoic acid may play an important functional role in the response of the heart to ischemia. C1 NIEHS, PULM PATHOBIOL LAB, NIH, RES TRIANGLE PK, NC 27709 USA. NIEHS, MOL BIOPHYS LAB, NIH, RES TRIANGLE PK, NC 27709 USA. NIEHS, EXPT PATHOL LAB, NIH, RES TRIANGLE PK, NC 27709 USA. DUKE UNIV, MED CTR, DEPT PATHOL, DURHAM, NC 27719 USA. UNIV TEXAS, SW MED CTR, DEPT MOL GENET, DALLAS, TX 75235 USA. RI Tomer, Kenneth/E-8018-2013; OI Falck, John/0000-0002-9219-7845 FU NHLBI NIH HHS [HL39752, R01 HL039752]; NIGMS NIH HHS [GM31278] NR 74 TC 168 Z9 186 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 9 PY 1997 VL 272 IS 19 BP 12551 EP 12559 DI 10.1074/jbc.272.19.12551 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WY829 UT WOS:A1997WY82900044 PM 9139707 ER PT J AU Zhen, SJ Dunn, IC Wray, S Liu, Y Chappell, PE Levine, JE Radovick, S AF Zhen, SJ Dunn, IC Wray, S Liu, Y Chappell, PE Levine, JE Radovick, S TI An alternative gonadotropin-releasing hormone (GnRH) RNA splicing product found in cultured GnRH neurons and mouse hypothalamus SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LUTEINIZING-HORMONE; GENE-EXPRESSION; GROWTH-FACTOR; LHRH NEURONS; BASAL FOREBRAIN; MESSENGER-RNA; FEMALE RATS; CELLS; SURGE AB Gonadotropin-releasing hormone (GnRH) is encoded by the proGnRH gene which contains four exons and three introns, In this study, two immortalized GnRH-expressing cell lines (Gn11 and NLT) were characterized, The NLT and Gn11 cells, derived from a same brain tumor in a transgenic mouse, display neuronal morphology and neuron-specific markers, However, NLT cells secrete much higher levels of GnRH than Gn11 cells, To delineate the mechanism underlying this difference, reverse transcriptase-polymerase chain reaction and RNase protection assays were performed to examine proGnRH gene expression. While the mature proGnRH mRNA was predominately expressed in NLT cells, Gn11 cells express an abundant short transcript, Sequence analysis revealed that this short transcript contains exons 1, 3, and 4, but not exon 2, which encodes the GnRH decapeptide, RNase protection assays demonstrated that NLT cells express much higher levels of mature proGnRH mRNA than Gn11 cells, The lower level of GnRH secreting capacity in Gn11 cells is due, in part, to decreased expression of mature proGnRH mRNA. When proGnRH gene expression in the mouse brain was examined, the same short splicing variant was observed in the olfactory area and preoptic area-anterior hypothalamus, But the prevalent transcript in these regions was the mature proGnRH mRNA, In contrast, only the mature proGnRH mRNA was found in the caudal hypothalamus. These results suggest that alternative splicing may be one of the mechanisms regulating proGnRH gene expression in the animal brain. C1 CHILDRENS HOSP,DIV ENDOCRINOL,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV GENET,BOSTON,MA 02115. NINCDS,NEUROCHEM LAB,NIH,BETHESDA,MD 20892. NORTHWESTERN UNIV,DEPT NEUROBIOL & PHYSIOL,EVANSTON,IL 60208. ROSLIN INST,DIV DEV & REPROD,ROSLIN EH25 9PS,MIDLOTHIAN,SCOTLAND. RI Dunn, Ian/C-7689-2013; OI Dunn, Ian/0000-0003-3630-0120; wray, susan/0000-0001-7670-3915 FU NICHD NIH HHS [HD30040] NR 30 TC 43 Z9 43 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 9 PY 1997 VL 272 IS 19 BP 12620 EP 12625 DI 10.1074/jbc.272.19.12620 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WY829 UT WOS:A1997WY82900054 PM 9139717 ER PT J AU Shuman, JD Cheong, JH Coligan, JE AF Shuman, JD Cheong, JH Coligan, JE TI ATF-2 and C/EBP alpha can form a heterodimeric DNA binding complex in vitro - Functional implications for transcriptional regulation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LIVER NUCLEAR-PROTEIN; SERUM-ALBUMIN GENE; LEUCINE ZIPPER; BASIC REGION; C-JUN; DIMERIZATION SPECIFICITY; 3T3-L1 PREADIPOCYTES; CRYSTAL-STRUCTURE; FACTOR FAMILY; FOS-JUN AB We screened an expression cDNA library with a radiolabeled C/EBP alpha fusion protein and isolated three independent cDNAs encoding ATF-S, a bZIP protein that binds cAMP response elements (CRE), This interaction requires the respective bZIP domains, which form a typical bZIP heterodimer with altered DNA binding selectivity, C/EBP alpha and ATF-2 homodimers bind CRE sites, but ATF-2:C/EBP alpha heterodimers do not. Heterodimers bind an asymmetric sequence composed of one consensus half-site for each monomer, and may thus have a unique regulatory function, As predicted, co-transfection of ATF-2 with C/EBP alpha results in decreased activation of transcription driven from consensus C/EBP-binding sites. In contrast, C/EBP alpha and ATF-2 function cooperatively to activate transcription driven by the asymmetric sequence. Both factors are expressed in liver, where immunoprecipitation experiments show that ATF-2 co-precipitates with C/EBP alpha. These results are consistent with the interpretation that C/EBP alpha and ATF-2 can associate in vivo. Moreover, the formation of ATF-S:C/EBP beta heterodimers suggests that cross-family dimerization with ATF-S may be a general property for C/EBP family proteins. RP Shuman, JD (reprint author), NIAID,MOL STRUCT LAB,NIH,TWINBROOK 2 BLDG,RM 103,ROCKVILLE,MD 20892, USA. NR 61 TC 74 Z9 75 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 MAY 9 PY 1997 VL 272 IS 19 BP 12793 EP 12800 DI 10.1074/jbc.272.19.12793 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WY829 UT WOS:A1997WY82900076 PM 9139739 ER PT J AU Meric, F Matsumoto, K Wolffe, AP AF Meric, F Matsumoto, K Wolffe, AP TI Regulated unmasking of in vivo synthesized maternal mRNA at oocyte maturation - A role for the chaperone nucleoplasmin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HISTONE MESSENGER-RNA; XENOPUS EGG EXTRACTS; Y-BOX PROTEINS; RIBONUCLEOPROTEIN PARTICLES; TRANSLATIONAL REGULATION; SPERM CHROMATIN; ACIDIC PROTEIN; SOMATIC-CELLS; TRANSCRIPTION; LAEVIS AB We examine the translational regulation of histone H4 mRNA when Xenopus laevis oocytes are induced to mature with progesterone, Histone H4 mRNA synthesized from plasmid templates microinjected into oocyte nuclei is translationally silenced (masked). This masked mRNA becomes translationally active only after oocyte maturation. In contrast, histone H4 mRNA injected into the oocyte cytoplasm is translationally active both before and after oocyte maturation. Thus, transcription in vivo is required to mask histone H4 mRNA and to allow subsequent translational regulation. Protein association with histone H4 mRNA synthesized in vivo was determined before and after oocyte maturation. UV cross linking of radiolabeled RNA to protein and immunoprecipitation of cross-linked proteins reveals an increased association of the chaperone nucleoplasmin with ribonucleoprotein particles dependent on the oocyte maturation process, The Y-box protein FRGY2 inhibits translation of histone H4 mRNA in vitro. Nucleoplasmin is able to partially relieve this repression, We discuss the potential role of nuleoplasmin in the remodeling of repressive ribonucleoprotein particles containing maternal mRNA to facilitate translational activation. C1 NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892. RI Matsumoto, Ken/F-9083-2013 OI Matsumoto, Ken/0000-0002-7864-3394 NR 53 TC 33 Z9 33 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 9 PY 1997 VL 272 IS 19 BP 12840 EP 12846 DI 10.1074/jbc.272.19.12840 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WY829 UT WOS:A1997WY82900082 PM 9139745 ER PT J AU Olsson, NU Salem, N AF Olsson, NU Salem, N TI Molecular species analysis of phospholipids SO JOURNAL OF CHROMATOGRAPHY B LA English DT Review DE reviews; phospholipids ID HIGH-PERFORMANCE LIQUID; CHROMATOGRAPHY MASS-SPECTROMETRY; HEPATIC PHOSPHATIDYLCHOLINE SYNTHESIS; POLAR CAPILLARY COLUMNS; FATTY-ACID COMPOSITION; REVERSED-PHASE HPLC; ROD OUTER SEGMENTS; GUINEA-PIG BRAIN; ETHANOLAMINE GLYCEROPHOSPHOLIPIDS; RAT-BRAIN AB The elucidation of phospholipid molecular species composition provides detailed structural information concerning various lipids and thus offers descriptions of crucial determinants of membrane physical and biological properties. Various methods differing in labor intensity, mode of separation and detection, type of calibration, as well as other factors, have been published. Thus precision and accuracy are expected to vary considerably between methods. Qualitative and quantitative aspects of different procedures for molecular species analysis of individual phospholipid classes are discussed in this review. Special emphasis has been given to the characterization of biological tissue samples. RP Olsson, NU (reprint author), NIAAA,LAB MEMBRANE BIOCHEM & BIOPHYS,NIH,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 122 TC 60 Z9 63 U1 2 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B PD MAY 9 PY 1997 VL 692 IS 2 BP 245 EP 256 DI 10.1016/S0378-4347(96)00507-5 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA XB520 UT WOS:A1997XB52000001 PM 9188812 ER PT J AU Perach, M Rubinek, T Hughes, SH Hizi, A AF Perach, M Rubinek, T Hughes, SH Hizi, A TI Analysis of HIV-2 RT mutants provides evidence that resistance of HIV-1 RT and HIV-2 RT to nucleoside analogs involves a repositioning of the template-primer SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE transcriptase; HIV-1; HIV-2; drug-resistance; nucleoside analogs ID IMMUNODEFICIENCY-VIRUS TYPE-1; MURINE LEUKEMIA-VIRUS; REVERSE-TRANSCRIPTASE; NONNUCLEOSIDE INHIBITORS; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; MUTATIONS; AIDS; SENSITIVITY; MECHANISMS AB Mutations that confer resistance to nucleoside analogs do not cluster around the deoxynucleotide triphosphate (dNTP) binding site. Instead, these mutations appear to lie along the groove in the enzyme where the template-primer binds. Based on such structural data and on complementary biochemical analyses, it has been suggested that resistance to nucleoside analogs involves repositioning of the template-primer. We have prepared mutations in HIV-2 RT that are the homologs of mutations that confer resistance to nucleoside analogs in HIV-1 RT. Analysis of the behavior of HIV-2 RT mutants (Leu74Val, Glu89Gly, Ser215Tyr, Leu74-Val/Ser215Tyr and Glu89Gly/Ser215Tyr) in vitro confirms the results obtained with HIV-1 RT: resistance is a function of the length of the template overhang. These analyses also suggest that the homolog in HIV-2 RT of one of the mutations that confers resistance to AZT in HIV-1 RT (Thr215Tyr) confers resistance by repositioning of the template-primer. C1 TEL AVIV UNIV,SACKLER SCH MED,DEPT CELL BIOL & HISTOL,IL-69978 TEL AVIV,ISRAEL. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 31 TC 19 Z9 20 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAY 9 PY 1997 VL 268 IS 3 BP 648 EP 654 DI 10.1006/jmbi.1997.0927 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WZ943 UT WOS:A1997WZ94300007 PM 9171288 ER PT J AU Yoon, HY Fanelli, A Grollman, EF Philp, NJ AF Yoon, HY Fanelli, A Grollman, EF Philp, NJ TI Identification of a unique monocarboxylate transporter (MCT3) in retinal pigment epithelium SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID RAT-THYROID CELLS; LACTATE; MEMBRANE; PHOTORECEPTORS; METABOLISM; EXPRESSION; CLONING AB The retinal pigment epithelium transports lactate between two tissue compartments, the interphotoreceptor matrix and the choriocapillaris. In this report we describe a 2.45-kb cDNA isolated from a chick cDNA RPE library that encodes a membrane protein found only in RPE cells. The deduced protein has 542 amino acids with twelve putative membrane spanning domains. The cDNA has been designated MCT3 based on its 45% identity in amino acid sequence and structural similarity with the monocarboxylate transporters MCT1 and MCT2. Stable transfectants (pCl-neo/MCT3), made in a rat thyroid epithelial cell line (FRTL-5), express MCT3 RNA. Transfectants had enhanced pyruvate uptake (used as a measure of lactate uptake) which was proton-dependent and inhibited by alpha-cyano-4-hydroxycinnamate. In summary, MCT3's unique expression in RPE cells, multiple potential phosphorylation sites, and basolateral distribution suggest that MCT3 may regulate lactate levels in the interphotoreceptor space. (C) 1997 Academic Press. C1 PENN COLL OPTOMETRY,PHILADELPHIA,PA 19141. NIDDK,BIOCHEM & METAB LAB,NIH,BETHESDA,MD. FU NEI NIH HHS [EY05508] NR 20 TC 104 Z9 107 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 MAY 8 PY 1997 VL 234 IS 1 BP 90 EP 94 DI 10.1006/bbrc.1997.6588 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WZ565 UT WOS:A1997WZ56500019 PM 9168967 ER PT J AU Loddick, SA Wong, ML Bongiorno, PB Gold, PW Licinio, J Rothwell, NJ AF Loddick, SA Wong, ML Bongiorno, PB Gold, PW Licinio, J Rothwell, NJ TI Endogenous interleukin-1 receptor antagonist is neuroprotective SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID IN-SITU HYBRIDIZATION; TRANSIENT FOREBRAIN ISCHEMIA; CENTRAL-NERVOUS-SYSTEM; MESSENGER-RNA; RAT-BRAIN; NEURONAL DAMAGE; LOCALIZATION; IL-1; CYTOKINES; FIBROBLASTS AB Interleukin-1 (IL-1) has been implicated in chronic and acute cerebral neuropathologies. IL-1 receptor antagonist (IL-1ra), a naturally occurring protein that binds to IL-1 receptors without inducing signal transduction, blocks several actions of IL-1. IL-1ra acts at the local level and it also circulates in the bloodstream. We now report evidence for a biological function of IL-1ra in the brain as an endogenous neuroprotective molecule. Cerebral expression of IL-1ra mRNA is induced rapidly by focal cerebral ischemia in rats, and inhibition of the action of IL-1ra, by passive immuno-neutralization, markedly enhances ischemic damage. To our knowledge this is the first report of an action of endogenous IL-1ra in the brain. Control of IL-1ra expression or action may therefore provide a useful therapeutic strategy to limit acute neurodegeneration. (C) 1997 Academic Press. C1 NIMH, CLIN NEUROENDOCRINOL BRANCH, NIH, INTRAMURAL RES PROGRAM, BETHESDA, MD 20892 USA. UNIV MANCHESTER, SCH BIOL SCI, MANCHESTER M13 9PT, LANCS, ENGLAND. RI Wong, Ma-Li/D-7903-2011; Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 33 TC 107 Z9 113 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 8 PY 1997 VL 234 IS 1 BP 211 EP 215 DI 10.1006/bbrc.1997.6436 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WZ565 UT WOS:A1997WZ56500043 PM 9168991 ER PT J AU Chun, TW Carruth, L Finzi, D Shen, XF DiGiuseppe, JA Taylor, H Hermankova, M Chadwick, K Margolick, J Quinn, TC Kuo, YH Brookmeyer, R Zeiger, MA BarditchCrovo, P Siliciano, RF AF Chun, TW Carruth, L Finzi, D Shen, XF DiGiuseppe, JA Taylor, H Hermankova, M Chadwick, K Margolick, J Quinn, TC Kuo, YH Brookmeyer, R Zeiger, MA BarditchCrovo, P Siliciano, RF TI Quantification of latent tissue reservoirs and total body viral load in HIV-1 Infection SO NATURE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PERIPHERAL-BLOOD; INSITU HYBRIDIZATION; IN-VIVO; T-CELL; LYMPHOCYTES; INDIVIDUALS; PLASMA; CD4; DNA AB The capacity of HIV-1 to establish latent infection of CD4(+) T cells may allow viral persistence despite immune responses and antiretroviral therapy. Measurements of infectious virus(1,2) and viral RNA(3,4) in plasma and of infectious virus(1), viral DNA(5-10) and viral messenger RNA species(11-14) in infected cells all suggest that HIV-1 replication continues throughout the course of infection. Uncertainty remains over what fraction of CD4(+) T cells are infected and whether there are latent reservoirs for the virus. We show here that during the asymptomatic phase of infection there is an extremely low total body load of latently infected resting CD4(+) T cells with replication-competent integrated provirus (< 10(7) cells). The most prevalent form of HIV-1 DNA in resting and activated CD4(+) T cells is a full-length, linear, unintegrated form that is not replication competent. The infection progresses even though at any given time in the lymphoid tissues integrated HIV-1 DNA is present in only a minute fraction of the susceptible populations, including resting and activated CD4(+) T cells and macrophages. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT SURG,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV HOSP,SCH HYG & PUBL HLTH,DEPT MOL MICROBIOL & IMMUNOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV HOSP,SCH HYG & PUBL HLTH,DEPT BIOSTAT,BALTIMORE,MD 21205. NIAID,NIH,BETHESDA,MD 20892. RI Quinn, Thomas/A-2494-2010 NR 30 TC 1234 Z9 1259 U1 5 U2 47 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD MAY 8 PY 1997 VL 387 IS 6629 BP 183 EP 188 DI 10.1038/387183a0 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WX945 UT WOS:A1997WX94500055 PM 9144289 ER PT J AU Shearer, WT Quinn, TC LaRussa, P Lew, JF Mofenson, L Almy, S Rich, K Handelsman, E Diaz, C Pagano, M Smeriglio, V Kalish, LA AF Shearer, WT Quinn, TC LaRussa, P Lew, JF Mofenson, L Almy, S Rich, K Handelsman, E Diaz, C Pagano, M Smeriglio, V Kalish, LA TI Viral load and disease progression in infants infected with human immunodeficiency virus type 1 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NATURAL-HISTORY; HIV-1 AB Background There are only limited data on human immunodeficiency virus type 1 (HIV-1) RNA in perinatally infected infants. Understanding the dynamics of HIV-1 infection and its relation to disease progression may help identify opportunities for effective antiviral treatment in infected infants. Methods We obtained plasma samples from 106 HIV-infected infants at birth; at 1, 2, 4, 6, 9, 12, 15, and 18 months of age; and subsequently every 6 months. HIV-1 RNA was assayed by means of a reverse-transcription polymerase chain reaction. The infants were born between 1990 and 1993, and only 21 percent of the infants' mothers received any treatment with zidovudine during pregnancy. Results Plasma HIV-1 RNA levels increased rapidly after birth, peaked at 1 to 2 months of age (median values at 1 and 2 months, 318,000 and 256,000 copies per milliliter, respectively), and then slowly declined to a median of 34,000 copies per milliliter at 24 months. Newborns with a first positive HIV-1 culture within 48 hours after birth had significantly higher HIV-1 RNA levels, although only during the first two months of life, than those with a first positive culture seven or more days after birth. Infants with a rapid progression of disease had higher peak HIV-I RNA levels in the first two months of life than those without rapid progression (median value, 724,000 vs. 219,000 copies per milliliter; P=0.006), as well as a higher geometric mean value during the first year of life (median value, 330,000 vs. 158,000 copies per milliliter; P=0.001). Conclusions in perinatally infected infants, HIV-1 RNA levels are high and decline only slowly during the first two years of life. Infants with very high viral loads in the first months of life are at increased risk for a rapid progression of disease, which suggests that early treatment with antiretroviral agents may be indicated for these infants. (C)1997, Massachusetts Medical Society. C1 BAYLOR COLL MED, DEPT PEDIAT, SECT ALLERGY & IMMUNOL, HOUSTON, TX 77030 USA. JOHNS HOPKINS UNIV, BALTIMORE, MD USA. NIAID, BETHESDA, MD 20892 USA. COLUMBIA PRESBYTERIAN MED CTR, DEPT VIROL, NEW YORK, NY USA. NICHHD, BETHESDA, MD 20892 USA. NEW ENGLAND RES INST, WATERTOWN, MA 02172 USA. UNIV ILLINOIS, CHICAGO, IL USA. SUNY, CTR HLTH SCI, BROOKLYN, NY USA. UNIV PUERTO RICO, SAN JUAN, PR 00936 USA. HARVARD UNIV, SCH PUBL HLTH, DEPT BIOSTAT, BOSTON, MA 02115 USA. NATL INST DRUG ABUSE, ROCKVILLE, MD USA. RI Quinn, Thomas/A-2494-2010; OI Mofenson, Lynne/0000-0002-2818-9808 FU NCRR NIH HHS [RR 00188]; NIAID NIH HHS [AI 36211, U01 AI 34840] NR 25 TC 348 Z9 356 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 8 PY 1997 VL 336 IS 19 BP 1337 EP 1342 DI 10.1056/NEJM199705083361901 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA WX851 UT WOS:A1997WX85100001 PM 9134873 ER PT J AU Vasan, RS Larson, MG Benjamin, EJ Evans, JC Levy, D AF Vasan, RS Larson, MG Benjamin, EJ Evans, JC Levy, D TI Left ventricular dilatation and the risk of congestive heart failure in people without myocardial infarction SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID M-MODE ECHOCARDIOGRAPHY; PROGNOSTIC IMPLICATIONS; FRAMINGHAM; MEN; DYSFUNCTION; SURVIVAL; DISEASE; VOLUME; PREDICTORS; INHIBITION AB Background Left ventricular dilatation is a well-recognized precursor of ventricular dysfunction and congestive heart failure after myocardial infarction. The effect of left ventricular dilatation on the risk of heart failure in people initially free of myocardial infarction is not known. Methods We examined the relation of the left ventricular end-diastolic and end-systolic internal dimensions, as measured by M-mode echocardiography, to the risk of congestive heart failure in 4744 subjects (2661 women and 2083 men) who had not sustained a myocardial infarction and who were free of congestive heart failure. We used sex-stratified proportional-hazards regression to assess the association between base-line left ventricular internal dimensions and the subsequent risk of congestive heart failure, after adjusting for age, blood pressure, hypertension treatment, body-mass index, diabetes, valve disease, and interim myocardial infarction. Results Over an 11-year follow-up period, congestive heart failure developed in 74 subjects (38 men and 36 women). The risk-factor-adjusted hazard ratio for congestive heart failure was 1.47 (95 percent confidence interval, 1.25 to 1.73) for an increment of 1 SD in the left ventricular end-diastolic dimension, indexed for height. We obtained similar results using the left ventricular end-systolic dimension (hazard ratio, 1.43; 95 percent confidence interval, 1.24 to 1.65). Conclusions An increase in left ventricular internal dimension is a risk factor for congestive heart failure in men and women who have not had a myocardial infarction. Knowledge of the left ventricular dimension improves predictions of the risk of congestive heart failure made on the basis of traditional risk factors, perhaps by aiding in the identification of subjects with subclinical left ventricular dysfunction. (C)1997, Massachusetts Medical Society. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY, FRAMINGHAM, MA 01701 USA. BETH ISRAEL HOSP, DIV CARDIOL, BOSTON, MA 02215 USA. BETH ISRAEL HOSP, DIV CLIN EPIDEMIOL, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. BOSTON UNIV, SCH MED, CARDIOL SECT, BOSTON, MA 02118 USA. BOSTON UNIV, SCH MED, DEPT PREVENT MED & EPIDEMIOL, BOSTON, MA 02118 USA. NHLBI, BETHESDA, MD 20892 USA. OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [N0I-HC-38038]; NINDS NIH HHS [2-ROI-NS17950-11] NR 35 TC 198 Z9 203 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 8 PY 1997 VL 336 IS 19 BP 1350 EP 1355 DI 10.1056/NEJM199705083361903 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA WX851 UT WOS:A1997WX85100003 PM 9134875 ER PT J AU Rosenstreich, DL Eggleston, P Kattan, M Baker, D Slavin, RG Gergen, P Mitchell, H McNiffMortimer, K Lynn, H Ownby, D Malveaux, F AF Rosenstreich, DL Eggleston, P Kattan, M Baker, D Slavin, RG Gergen, P Mitchell, H McNiffMortimer, K Lynn, H Ownby, D Malveaux, F TI The role of cockroach allergy and exposure to cockroach allergen in causing morbidity among inner-city children with asthma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT Annual International Conference of the American-Thoracic-Society CY MAY 11-22, 1996 CL NEW ORLEANS, LA SP Amer Thorac Soc ID HOUSE-DUST MITE; IMMEDIATE HYPERSENSITIVITY; INDOOR ALLERGENS; RISK-FACTORS; SENSITIZATION; PURIFICATION; PREVALENCE; CHILDHOOD; ANTIGENS; ALTITUDE AB Background It has been hypothesized that asthma-related health problems are most severe among children in inner-city areas who are allergic to a specific allergen and also exposed to high levels of that allergen in bedroom dust. Methods From November 1992 through October 1993, we recruited 476 children with asthma (age, four to nine years) from eight inner-city areas in the United States. Immediate hypersensitivity to cockroach, house-dust-mite, and cat allergens was measured by skin testing. We then measured major allergens of cockroach (Bla g 1), dust mites (Der p 1 and Der f 1), and cat dander (Fel d 1) in household dust using monoclonal-antibody-based enzyme-linked immunosorbent assays. High levels of exposure were defined according to proposed thresholds for causing disease. Data on morbidity due to asthma were collected at base line and over a one-year period. Results Of the children, 36.8 percent were allergic to cockroach allergen, 34.9 percent to dust-mite allergen, and 22.7 percent to cat allergen. Among the children's bedrooms, 50.2 percent had high levels of cockroach allergen in dust, 9.7 percent had high levels of dust-mite allergen, and 12.6 percent had high levels of cat allergen. After we adjusted for sex, score on the Child Behavior Checklist, and family history of asthma, we found that children who were both allergic to cockroach allergen and exposed to high levels of this allergen had 0.37 hospitalization a year, as compared with 0.11 for the other children (P=0.001), and 2.56 unscheduled medical visits for asthma per year, as compared with 1.43 (P<0.001). They also had significantly more days of wheezing, missed school days, and nights with lost sleep, and their parents or other care givers were awakened during the night and changed their daytime plans because of the child's asthma significantly more frequently. Similar patterns were not found for the combination of allergy to dust mites or cat dander and high levels of the allergen. Conclusions The combination of cockroach allergy and exposure to high levels of this allergen may help explain the frequency of asthma-related health problems in inner-city children. (C)1997, Massachusetts Medical Society. C1 JOHNS HOPKINS UNIV,SCH MED,DIV PEDIAT ALLERGY & IMMUNOL,BALTIMORE,MD. MT SINAI SCH MED,DEPT PEDIAT,NEW YORK,NY. UNIV CALIF IRVINE,CTR ENVIRONM & OCCUPAT HLTH,IRVINE,CA 92717. ST LOUIS UNIV,SCH MED,DEPT MED,DIV ALLERGY IMMUNOL,ST LOUIS,MO 63104. NIAID,BETHESDA,MD 20892. NEW ENGLAND RES INST,WATERTOWN,MA 02172. HENRY FORD HOSP,DIV ALLERGY,DETROIT,MI 48202. HOWARD UNIV,WASHINGTON,DC 20059. RP Rosenstreich, DL (reprint author), ALBERT EINSTEIN COLL MED,DIV ALLERGY IMMUNOL,DEPT MED,1300 MORRIS PK AVE,BRONX,NY 10461, USA. FU NIAID NIH HHS [AI-30752, AI-30756, UO1 AI-30751] NR 33 TC 854 Z9 870 U1 5 U2 33 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 8 PY 1997 VL 336 IS 19 BP 1356 EP 1363 DI 10.1056/NEJM199705083361904 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA WX851 UT WOS:A1997WX85100004 PM 9134876 ER PT J AU Young, NS Maciejewski, J AF Young, NS Maciejewski, J TI Mechanisms of disease - The pathophysiology of acquired aplastic anemia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID HEMATOPOIETIC PROGENITOR CELLS; COLONY-STIMULATING FACTOR; ANTI-THYMOCYTE GLOBULIN; NECROSIS-FACTOR-ALPHA; MARROW STROMAL CELLS; HUMAN BONE-MARROW; INTERFERON-GAMMA; ANTILYMPHOCYTE GLOBULIN; FAS ANTIGEN; T-CELLS RP Young, NS (reprint author), NHLBI,HEMATOL BRANCH,NIH,BLDG 10,RM 7C103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 73 TC 302 Z9 315 U1 3 U2 7 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 8 PY 1997 VL 336 IS 19 BP 1365 EP 1372 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA WX851 UT WOS:A1997WX85100006 PM 9134878 ER PT J AU Fan, SJ Chang, JK Smith, ML Duba, D Fornace, AJ OConnor, PM AF Fan, SJ Chang, JK Smith, ML Duba, D Fornace, AJ OConnor, PM TI Cells lacking CIP1/WAF1 genes exhibit preferential sensitivity to cisplatin and nitrogen mustard SO ONCOGENE LA English DT Article DE cell cycle checkpoints; chemosensitivity; p53; CIP1/WAF1; radiation; DNA repair ID NUCLEOTIDE EXCISION-REPAIR; CYCLIN-DEPENDENT KINASES; P53-MEDIATED G(1) ARREST; P53 TUMOR-SUPPRESSOR; DNA-REPLICATION; CROSS-LINKS; P21; INHIBITOR; PROTEIN; LINES AB We have previously shown that p53 disruption sensitizes certain cancer cell types to cisplatin (CDDP) (Fan et al., 1995). In the present study we investigated the role of the p53 downstream effector, p21(CIP1/WAF1) (p21), in this sensitization, Studies were performed in human colon cancer HCT-116 cells and murine embryonic fibroblasts (MEF) with intact versus disrupted p21 genes, For comparison, HCT-116 cells lacking p53 function were also prepared through stable transfection with the human papillomavirus type-16 E6 gene. HCT-116/E6 cells were found to be more sensitive than control transfectants to CDDP and another DNA crosslinking agent, nitrogen mustard (HN2). HCT-116 cells with disrupted p21 genes also exhibited greater CDDP and HN2-sensitivity than parental HCT-116 cells. In contrast, the clonogenic survival of HCT-116 cells exposed to ionizing radiation, adriamycin, taxol or vincristine was not affected by p53 or p21 disruption. Sensitization of HCT-116/p21(-/-) cells to CDDP and HN2 was not limited to the HCT-116 cell background since MEF from p21 knockout mice were also more sensitive to these DNA crosslinking agents. Investigations into a possible cause of this enhanced sensitivity revealed that HCT-116 cells lacking p53 or p21 function exhibited a reduced ability to repair cisplatin-damaged CAT-reporter plasmids transfected into the cells. In addition, we found that HCT-116/p21(-/-) cells were much more susceptible to HN2-induced cell cycle delay than parental cells. Our results suggest that p21 disruption preferentially sensitizes at least some cell types to DNA crosslinking agents. C1 NCI,NIH,MOL PHARMACOL LAB,BETHESDA,MD 20892. NCI,NIH,DIV BASIC SCI,BETHESDA,MD 20892. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 40 TC 149 Z9 152 U1 0 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 8 PY 1997 VL 14 IS 18 BP 2127 EP 2136 DI 10.1038/sj.onc.1201052 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA WX938 UT WOS:A1997WX93800001 PM 9174048 ER PT J AU Simpson, S Woodworth, CD DiPaolo, JA AF Simpson, S Woodworth, CD DiPaolo, JA TI Altered expression of Erg and Ets-2 transcription factors is associated with genetic changes at 21q22.2-22.3 in immortal and cervical carcinoma cell lines SO ONCOGENE LA English DT Article DE ets and erg; pulsed field gel electrophoresis; papillomavirus HPV-16; cervical carcinoma ID HUMAN PAPILLOMAVIRUS TYPE-16; HUMAN EPITHELIAL-CELLS; HUMAN KERATINOCYTES; HUMAN CHROMOSOME-21; NEOPLASTIC TRANSFORMATION; PHYSICAL MAP; TEL GENE; DNA; RAS; TRANSLOCATION AB Human Papillomavirus (HPV) type 16 is the most frequently detected HPV in cervical cancer. Although epidemiologic and experimental evidence indicates a prominent role for HPV infection in the development of this disease, other factors are also involved, Altered expression of the sts family transcription factors erg and ets-2 was found associated with the development of cervical carcinoma. Overexpression also occurred in a HPV-16-immortalized cervical cell line, CX16-2, which has HPV integrated at a translocation breakpoint t(19;21) involving 21q22.2-22.3, where these genes have been mapped. Six of 10 cervical carcinoma cell lines overexpressed ets-2 RNA suggesting an association of overexpression with cervical cell neoplasia. A clonally related pair of cervical carcinoma cell lines, C-4I and C-4II, showed differential expression of erg and ets-2. C-4I overexpressed ets-2 RNA compared to normal cervical cells and C-4II, C-4II expressed a 5.3 kb erg transcript not seen in C-4I, ectocervical cells or other cervical carcinoma cell lines examined. Pulsed field gel electrophoresis was used to analyse changes in DNA fragments related to structural changes and to construct a physical map encompassing erg and ets-2. Alterations in erg and ets-2 RNA expression in each of three different cell lines examined were associated,vith translocations. Association between altered expression of erg and ets-2 and altered regional structural suggests that these genes are important targets in cervical carcinogenesis. C1 NCI,BIOL LAB,BETHESDA,MD 20892. NR 63 TC 20 Z9 22 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 8 PY 1997 VL 14 IS 18 BP 2149 EP 2157 DI 10.1038/sj.onc.1201058 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA WX938 UT WOS:A1997WX93800003 PM 9174050 ER PT J AU Jones, TL Karavanova, I Chong, L Zhou, RP Daar, IO AF Jones, TL Karavanova, I Chong, L Zhou, RP Daar, IO TI Identification of XLerk, an Eph family ligand regulated during mesoderm induction and neurogenesis in Xenopus laevis SO ONCOGENE LA English DT Article DE Eph ligand; xenopus development; nervous system ID RECEPTOR TYROSINE KINASES; GROWTH-FACTOR; NEURAL CREST; MOLECULAR-CLONING; CDNA CLONING; EXPRESSION; PROTEIN; EMBRYOS; GENES; TRANSITION AB We have isolated and characterized the first Xenopus transmembrane Eph ligand, XLerk (Xenopus Ligand for Eph Receptor Tyrosine Kinases). While this ligand has 72% identity with the closest mammalian family member, Lerk-2, it is the cytoplasmic domain of this molecule that is the most conserved domain with 95% identity, XLerk exists as a maternally expressed mRNA, however, expression of transcripts and protein increase during gastrulation and again in the late swimming tadpole stage. In the adult, XLerk is expressed at low levels in mast adult tissues with increased levels observed in the kidney, oocytes, ovary and testis. While low levels of XLerk expression are observed in the adult brain, ill situ hybridization analysis demonstrates prominent expression in the developing olfactory system, retina, hindbrain, cranial ganglia, and somites, Furthermore, we have shown that XLerk transcripts are significantly elevated during mesoderm induction caused by activin and FGF, but not during noggin-induced neuralization. These results suggest a role for XLerk in the developing mesenchymal and nervous tissue. C1 NCI,FREDERICK CANC RES & DEV CTR,LAB LEUKOCYTE BIOL,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RUTGERS STATE UNIV,CANC RES LAB,PISCATAWAY,NJ 08855. OI Daar, Ira/0000-0003-2657-526X NR 57 TC 19 Z9 20 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 8 PY 1997 VL 14 IS 18 BP 2159 EP 2166 DI 10.1038/sj.onc.1201082 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA WX938 UT WOS:A1997WX93800004 PM 9174051 ER PT J AU Hoeg, JM AF Hoeg, JM TI Evaluating coronary heart disease risk - Tiles in the mosaic SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ULTRAFAST COMPUTED-TOMOGRAPHY; ATHEROSCLEROTIC LESIONS; BLOOD-PRESSURE; ARTERY DISEASE; PREVENTION; QUANTIFICATION; HYPERCHOLESTEROLEMIA; QUANTITATION; PRAVASTATIN; REGRESSION RP Hoeg, JM (reprint author), NHLBI,SECT CELL BIOL,MOL DIS BRANCH,BLDG 10,ROOM 7N115,10 CTR DR,MSC 1666,BETHESDA,MD 20892, USA. NR 43 TC 40 Z9 42 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 7 PY 1997 VL 277 IS 17 BP 1387 EP 1390 DI 10.1001/jama.277.17.1387 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA WW261 UT WOS:A1997WW26100029 PM 9134945 ER PT J AU Breslow, RA Shay, JW Gazdar, AF Srivastava, S AF Breslow, RA Shay, JW Gazdar, AF Srivastava, S TI Telomerase and early detection of cancer: A National Cancer Institute workshop SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material C1 NCI,EARLY DETECT BRANCH,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. NCI,APPL RES BRANCH,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. UNIV TEXAS,SW MED CTR,DEPT CELL BIOL,DALLAS,TX. UNIV TEXAS,SW MED CTR,DEPT PATHOL,HAMON CANC CTR,DALLAS,TX. RI Shay, Jerry/F-7878-2011 NR 23 TC 47 Z9 52 U1 0 U2 3 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 7 PY 1997 VL 89 IS 9 BP 618 EP 623 DI 10.1093/jnci/89.9.618 PG 6 WC Oncology SC Oncology GA WX656 UT WOS:A1997WX65600008 PM 9150185 ER PT J AU deGruijl, TD Bontkes, HJ Walboomers, JMM Schiller, JT Stukart, MJ Groot, BS Chabaud, MMR Remmink, AJ Verheijen, RHM Helmerhorst, TJM Meijer, CJLM Scheper, RJ AF deGruijl, TD Bontkes, HJ Walboomers, JMM Schiller, JT Stukart, MJ Groot, BS Chabaud, MMR Remmink, AJ Verheijen, RHM Helmerhorst, TJM Meijer, CJLM Scheper, RJ TI Immunoglobulin G responses against human papillomavirus type 16 virus-like particles in a prospective nonintervention cohort study of women with cervical intraepithelial neoplasia SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID POLYMERASE CHAIN-REACTION; L1 PROTEIN; INFECTION; IMMUNIZATION; PERSPECTIVE; ANTIBODIES; EXPRESSION; DYSPLASIA; GENOTYPES; CAPSIDS AB Background: Infection with cancer-linked human papillomavirus (HPV) types such as HPV type 16 (HPV16) is the most important risk factor in the development of cervical cancer. It has been shown that immunoglobulin G (IgG) antibody responses against HPV16 virus-like particles (VLPs) are specifically associated with genital HPV16 infection. Purpose: The aim of this study was to determine the temporal relationships between the presence of HPV16 VLP-specific IgGs, HPV16 infection patterns, and the course of premalignant cervical disease. Methods: Plasma samples from 133 women who had been diagnosed originally with mild to moderate cervical dyskaryosis and enrolled in a prospective nonintervention cohort study conducted in Amsterdam. The Netherlands, from 1991 through 1996 were analyzed for the presence of HPV16 VLP-specific IgGs by use of an enzyme-linked immunosorbent assay. A detailed analysis was performed on 43 women with different HPV16 infection patterns during a follow-up period of 10-34 months. Progression or regression of cervical intraepithelial neoplasia (CIN) lesions was monitored by cytologic and colposcopic testing at intervals of 3-4 months. HPV typing in cervical smears was performed by use of a polymerase chain reaction-based assay. Statistical analysis of the serologic data was performed by use of the Mann-Whitney U test or 2 x 2 table analyses. Results: The presence of HPV16 VLP-specific IgGs in the plasma of the patients was found to be associated with the presence of HPV16 DNA in the cervical smear. Significantly higher proportions of patients with persistent HPV16 infections (i.e., who were polymerase chain reaction positive in three to 11 consecutive tests) than of patients with cleared HPV16 infections were found to be positive for the presence of HPV16 VLP-specific IgGs (18 [69.2%] of 26 versus nine [28.1%] of 32, respectively; P = .003), HPV16 VLP-specific IgGs mere consistently detected in all women (n = 11) who were persistently HPV16 DNA positive during follow-up and whose disease ultimately progressed to CIN III (histologically diagnosed severe dysplasia or carcinoma in situ). Conclusion: HPV16 VLP-specific IgG responses are present in the plasma of a majority of patients with persistent HPV16 infections and histologically confirmed high-grade lesions but only in a smaller subset of patients with cleared HPV16 infections and either normal cervical histology or low-grade CIN lesions. Implications: These results suggest that HPV16 VLP-specific antibodies are not responsible for the clearance of virally induced CIN lesions but that they might, in patients with persistent HPV16 infections, be indicative of an increased cervical cancer risk. C1 FREE UNIV AMSTERDAM HOSP,DEPT PATHOL,NL-1007 MB AMSTERDAM,NETHERLANDS. FREE UNIV AMSTERDAM HOSP,DEPT OBSTET & GYNECOL,NL-1007 MB AMSTERDAM,NETHERLANDS. UNIV TOURS,FAC PHARM,LAB IMMUNOL MALAD INFECT,F-37041 TOURS,FRANCE. NCI,CELLULAR ONCOL LAB,DIV BASIC SCI,BETHESDA,MD 20892. NR 30 TC 75 Z9 75 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 MAY 7 PY 1997 VL 89 IS 9 BP 630 EP 638 DI 10.1093/jnci/89.9.630 PG 9 WC Oncology SC Oncology GA WX656 UT WOS:A1997WX65600010 PM 9150187 ER PT J AU Longo, DL AF Longo, DL TI You say tomato and I say tomahto: Getting a handle on pronouncing apoptosis SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter RP Longo, DL (reprint author), NIA,GERONTOL RES CTR,NIH,4940 EASTERN AVE,RM 1E07,BALTIMORE,MD 21224, USA. NR 2 TC 1 Z9 1 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 MAY 7 PY 1997 VL 89 IS 9 BP 657 EP 657 PG 1 WC Oncology SC Oncology GA WX656 UT WOS:A1997WX65600014 PM 9150191 ER PT J AU Curtis, RE Boice, JD Hankey, BF Fraumeni, JF AF Curtis, RE Boice, JD Hankey, BF Fraumeni, JF TI Second cancers after adjuvant tamoxifen therapy for breast cancer - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI,RADIAT EPIDEMIOL BRANCH,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. NCI,CANC STAT BRANCH,BETHESDA,MD 20892. NR 4 TC 1 Z9 1 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 7 PY 1997 VL 89 IS 9 BP 658 EP 659 PG 2 WC Oncology SC Oncology GA WX656 UT WOS:A1997WX65600016 ER PT J AU Weiderpass, E Gridley, G Nyren, O Ekbom, A Persson, I Adami, HO AF Weiderpass, E Gridley, G Nyren, O Ekbom, A Persson, I Adami, HO TI Diabetes mellitus and risk of large bowel cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID COLORECTAL-CANCER C1 UNIV UPPSALA HOSP,DEPT CANC EPIDEMIOL,S-75185 UPPSALA,SWEDEN. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. NCI,BIOSTAT BRANCH,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. UNIV BOSTON HOSP,DEPT CANC EPIDEMIOL,BOSTON,MA 02118. RI Weiderpass, Elisabete/M-4029-2016 OI Weiderpass, Elisabete/0000-0003-2237-0128 NR 9 TC 73 Z9 73 U1 1 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 7 PY 1997 VL 89 IS 9 BP 660 EP 661 PG 2 WC Oncology SC Oncology GA WX656 UT WOS:A1997WX65600019 PM 9150194 ER PT J AU Lubin, JH Boice, JD AF Lubin, JH Boice, JD TI Untitled - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID BIASES C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. NR 8 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 MAY 7 PY 1997 VL 89 IS 9 BP 664 EP 665 PG 2 WC Oncology SC Oncology GA WX656 UT WOS:A1997WX65600025 ER PT J AU Rao, PV Gonzalez, P Persson, B Jornvall, H Garland, D Zigler, JS AF Rao, PV Gonzalez, P Persson, B Jornvall, H Garland, D Zigler, JS TI Guinea pig and bovine xi-crystallins have distinct functional characteristics highlighting replacements in otherwise similar structures SO BIOCHEMISTRY LA English DT Article ID URACIL DNA-GLYCOSYLASE; RNA-BINDING PROTEIN; ZETA-CRYSTALLIN; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; ALCOHOL-DEHYDROGENASE; QUINONE REDUCTASE; LENS CRYSTALLINS; EYE LENS; HEREDITARY CATARACTS; GENE AB zeta-Crystallin, a major cytosolic protein of guinea pig lens, has been characterized as an NADPH: quinone oxidoreductase (EC 1.6.5.5) [Rao et al. (1992) J. Biol. Chem. 267, 97-103]. A bovine lens homolog with 83% sequence identity was found to have very different functional characteristics. While the bovine lens zeta-crystallin exhibits similar physicochemical properties, such as molecular weight, hydropathy profile, and predicted secondary structure, and exhibits strong immunological cross-reactivity with the guinea pig and human lens zeta-crystallins, it shows minimal quinone oxidoreductase activity. On the other hand, bovine lens zeta-crystallin, but not guinea pig zeta-crystallin, showed a strong binding affinity to single-stranded DNA (ssDNA) that could be competed with NADPH, the specific cofactor of zeta-crystallin. NADH and dextran sulfate did not affect this characteristic of bovine zeta-crystallin and the enzyme showed no binding affinity for the heparin-Ultragel A4R. Two-dimensional electrophoresis of bovine lens zeta-crystallin showed a distinct pattern of posttranslational charge modification as compared to the guinea pig protein. Alignment of eight zeta-crystallin sequences, and computer modelling of the bovine and human forms based on the crystallographically analyzed Escherichia coli form, suggest that if loss of a functional residue accounts for the lowered catalytic activity of the bovine protein, Tyr 52 of the E. coli enzyme, and the equivalent Tyr present in all known mammalian forms except the bovine, is the likely candidate. In the bovine form this tyrosine is replaced by histidine. C1 KAROLINSKA INST,DEPT MED BIOCHEM & BIOPHYS,STOCKHOLM,SWEDEN. RP Rao, PV (reprint author), NEI,NIH,6 CTR DR,MSC 2735,BETHESDA,MD 20892, USA. NR 50 TC 27 Z9 28 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 MAY 6 PY 1997 VL 36 IS 18 BP 5353 EP 5362 DI 10.1021/bi9622985 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WY063 UT WOS:A1997WY06300007 PM 9154917 ER PT J AU Gruschus, JM Tsao, DHH Wang, LH Nirenberg, M Ferretti, JA AF Gruschus, JM Tsao, DHH Wang, LH Nirenberg, M Ferretti, JA TI Interactions of the vnd/NK-2 homeodomain with DNA by nuclear magnetic resonance spectroscopy: Basis of binding specificity SO BIOCHEMISTRY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; NK-2 HOMEOBOX GENE; CRYSTAL-STRUCTURE; ANTENNAPEDIA HOMEODOMAIN; DROSOPHILA-MELANOGASTER; MULTIDIMENSIONAL NMR; RECOGNITION HELIX; PEPTIDE COMPLEX; PROTEIN; SEQUENCE AB The interactions responsible for the nucleotide sequence-specific binding of the vnd/NK-2 homeodomain of Drosophila melanogaster to its consensus DNA binding site have been identified. A three-dimensional structure of the vnd/NK-2 homeodomain-DNA complex is presented, with emphasis on the structure of regions of observed protein-DNA contacts. This structure is based on protein-DNA distance restraints derived from NMR data, along with homology modeling, solvated molecular dynamics, and results from methylation and ethylation interference experiments. Helix III of the homeodomain binds in the major groove of the DNA and the N-terminal arm binds in the minor groove, in analogy with other homeodomain-DNA complexes whose structures have been reported. The vnd/NK-2 homeodomain recognizes the unusual DNA consensus sequence 5'-CAAGTG-3'. The roles in sequence specificity and strength of binding of individual amino acid residues that make contact with the DNA are described. We show, based primarily on the observed protein-DNA contacts, that the interaction of Y54 with the DNA is the major determinant of this uncommon nucleotide binding specificity in the vnd/NK-2 homeodomain-DNA complex. C1 NHLBI,LAB BIOCHEM GENET,NIH,BETHESDA,MD 20892. NHLBI,BIOPHYS CHEM LAB,NIH,BETHESDA,MD 20892. NR 49 TC 70 Z9 71 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 6 PY 1997 VL 36 IS 18 BP 5372 EP 5380 DI 10.1021/bi9620060 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WY063 UT WOS:A1997WY06300009 PM 9154919 ER PT J AU Herzberg, U Eliav, E Dorsey, JM Gracely, RH Kopin, IJ AF Herzberg, U Eliav, E Dorsey, JM Gracely, RH Kopin, IJ TI NGF involvement in pain induced by chronic constriction injury of the rat sciatic nerve SO NEUROREPORT LA English DT Article DE inflammation; nerve growth factor; neuropathy; pain ID DORSAL-ROOT GANGLIA; GROWTH-FACTOR; PERIPHERAL MONONEUROPATHY; NEUROPATHIC PAIN; SENSORY NEURONS; HYPERALGESIA; MODEL; MICE; DISORDERS; ALLODYNIA AB CHRONIC constriction injury (CCI) of the rat sciatic nerve, which within 3 days induces thermal and mechanical hyperalgesia and mechanical allodynia, is used as a model for pain resulting from nerve injury. Involvement of nerve growth factor (NGF) in the development of this hyperalgesia is suggested by the increase in the level of mRNA encoding NGF in cells in the injured area and in dorsal root ganglia at the level of the lesion and the greatly increased NGF levels (determined by ELISA) in the ganglia ipsilateral to the CCI. Application of antiserum to NGF at the site of CCI delayed the appearance of hyperalgesia, whereas pre-immune serum appeared to enhance it. These results are consistent with the view that NGF is an important factor in the appearance of hyperalgesia associated with unilateral mononeuropathy. C1 NIDR,BETHESDA,MD 20892. RP Herzberg, U (reprint author), NINCDS,CLIN NEUROSCI BRANCH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 25 TC 114 Z9 114 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAY 6 PY 1997 VL 8 IS 7 BP 1613 EP 1618 DI 10.1097/00001756-199705060-00012 PG 6 WC Neurosciences SC Neurosciences & Neurology GA XC956 UT WOS:A1997XC95600013 PM 9189901 ER PT J AU Miner, JH Patton, BL Lentz, SI Gilbert, DJ Jenkins, NA Copeland, NG Sanes, JR AF Miner, JH Patton, BL Lentz, SI Gilbert, DJ Jenkins, NA Copeland, NG Sanes, JR TI The laminin alpha chains: Expression, developmental transitions, and chromosomal locations of alpha 1-5, identification of heterotrimeric laminins 8-11, and cloning of a novel alpha 3 isoform SO JOURNAL OF CELL BIOLOGY LA English DT Article ID GENETIC-LINKAGE MAP; PROTEIN S-LAMININ; A-CHAIN; BASEMENT-MEMBRANES; MONOCLONAL-ANTIBODIES; NEUROMUSCULAR-JUNCTION; HEPARIN-BINDING; BASAL LAMINA; LONG ARM; MUSCULAR-DYSTROPHY AB Laminin trimers composed of alpha, beta, and gamma chains are major components of basal laminae (BLs) throughout the body. To date, three ct chains (alpha 1-3) have been shown to assemble into at least seven heterotrimers (called laminins 1-7). Genes encoding two additional alpha chains (alpha 4 and alpha 5) have been cloned, but little is known about their expression, and their protein products have not been identified. Here we generated antisera to recombinant alpha 4 and alpha 5 and used them to identify authentic proteins in tissue extracts. Immunoprecipitation and immunoblotting showed that alpha 4 and alpha 5 assemble into four novel laminin heterotrimers (laminins 8-11: alpha 4 beta 1 gamma 1, alpha 4 beta 2 gamma 1, alpha 5 beta 1 gamma 1, and alpha 5 beta 2 gamma 1, respectively). Using a panel of nucleotide and antibody probes, we surveyed the expression of alpha 1-5 in murine tissues. All five chains were expressed in both embryos and adults, but each was distributed in a distinct pattern at both RNA and protein levels. Overall, alpha 4 and alpha 5 exhibited the broadest patterns of expression, while expression of alpha 1 was the most restricted. Immunohistochemical analysis of kidney, lung, and heart showed that the ct chains were confined to extracellular matrix and, with few exceptions, to BLs. All developing and adult BLs examined contained at least one alpha chain, all alpha chains were present in multiple BLs, and some BLs contained two or three a chains. Detailed analysis of developing kidney revealed that some individual BLs, including those of the tubule and glomerulus, changed in laminin chain composition as they matured, expressing up to three different alpha chains and two different beta chains in an elaborate and dynamic progression. Interspecific backcross mapping of the five alpha chain genes revealed that they are distributed on four mouse chromosomes. Finally, we identified a novel full-length alpha 3 isoform encoded by the Lama3 gene, which was previously believed to encode only truncated chains. Together, these results reveal remarkable diversity in BL composition and complexity in BL development. C1 WASHINGTON UNIV,SCH MED,DEPT ANAT & NEUROBIOL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT INTERNAL MED,DIV RENAL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT NEUROL,ST LOUIS,MO 63110. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. NR 91 TC 519 Z9 524 U1 0 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAY 5 PY 1997 VL 137 IS 3 BP 685 EP 701 DI 10.1083/jcb.137.3.685 PG 17 WC Cell Biology SC Cell Biology GA WY019 UT WOS:A1997WY01900013 PM 9151674 ER PT J AU Hemmer, B Fleckenstein, BT Vergelli, M Jung, G McFarland, H Martin, R Wiesmuller, KH AF Hemmer, B Fleckenstein, BT Vergelli, M Jung, G McFarland, H Martin, R Wiesmuller, KH TI Identification of high potency microbial and self ligands for a human autoreactive class II-restricted T cell clone SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MYELIN BASIC-PROTEIN; PEPTIDE COMBINATORIAL LIBRARIES; AUTOIMMUNITY; RECOGNITION; BINDING; SPECIFICITY; DISCOVERY; RECEPTOR; VIRUS AB CD4(+) class II-restricted T cells specific for self antigens are thought to be involved in the pathogenesis of most human autoimmune diseases and molecular mimicry between foreign and self ligands has been implicated as a possible mechanism for their activation. In this report we introduce combinatorial peptide libraries as a powerful tool to identify cross-reactive Ligands for these T cells. The antigen recognition of a CD4(+) T cell clone (TCC) specific for myelin basic protein peptide (MBP) (86-96) was dissected by the response to a set of 220 11-mer peptide sublibraries. Based on the results obtained with the libraries for each position of the antigen, artificial peptides were found that induced proliferative responses at much lower concentrations than MBP(86-96). In addition stimulatory ligands derived from protein sequences of self and microbial proteins were identified, some of them even more potent agonists than MBP(86-96). These results indicate that: (ii) for at least some autoreactive CD4(+) T cells antigen recognition is highly degenerate; (b) the autoantigen used to establish the TCC represents only a suboptimal ligand for the TCC; (c) a completely random and unbiased approach such as combinatorial Peptide libraries can decrypt the spectrum of stimulatory ligands for a T cell receptor (TCR). C1 UNIV TUBINGEN,INST ORGAN CHEM,D-72076 TUBINGEN,GERMANY. UNIV TUBINGEN,NATUNWISSENSCHAFTLICHES & MED INST,D-72762 REUTLINGEN,GERMANY. UNIV TUBINGEN,SCH MED,DEPT NEUROL,D-72076 TUBINGEN,GERMANY. RP Hemmer, B (reprint author), NINCDS,NIH,NEUROIMMUNOL BRANCH,BLDG 10 ROOM 5B16,10 CTR DR,MSC 1400,BETHESDA,MD 20892, USA. NR 31 TC 271 Z9 274 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 5 PY 1997 VL 185 IS 9 BP 1651 EP 1659 DI 10.1084/jem.185.9.1651 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA WY117 UT WOS:A1997WY11700014 PM 9151902 ER PT J AU JonesBrando, LV Buthod, JL Holland, LE Yolken, RH Torrey, EF AF JonesBrando, LV Buthod, JL Holland, LE Yolken, RH Torrey, EF TI Metabolites of the antipsychotic agent clozapine inhibit the replication of human immunodeficiency virus type 1 SO SCHIZOPHRENIA RESEARCH LA English DT Article DE antipsychotic; antiviral; schizophrenia; virus ID HERPES-SIMPLEX VIRUS; SCHIZOPHRENIC-PATIENTS; PSYCHOTROPIC-DRUGS; RECEPTOR OCCUPANCY; LITHIUM-CARBONATE; HIV; INFECTION; PHARMACOKINETICS; CHLORIDE; THERAPY AB Schizophrenia is a serious and often debilitating neuropsychiatric disease of worldwide importance, Current therapy relies on the use of typical antipsychotic medications, which specifically inhibit binding of ligand at the D2 dopamine receptor, and atypical medications which display little activity for this receptor interaction. While atypical antipsychotic agents have been shown to variably inhibit other neuroreceptor-ligand interactions, the exact mechanisms for the therapeutic efficacy of these medications have not been completely defined. Clozapine, an atypical antipsychotic, and nine of its metabolites were studied in vitro for possible antiviral activity against a model of a human neurotropic virus, human immunodeficiency virus type 1 (HIV-1). In an assay for inhibition of virus-induced cytopathic effect (CPE) two metabolites demonstrated antiviral activity (ID50 = 37-85 mu g/ml) (119-289 mu M), while other atypical or novel antipsychotics as well as typical medications had no effect, Based on an ELISA, four chemically similar metabolites inhibited the production of p24, the major internal antigen of HIV (ID50 = 11.6-15.7 mu g/ml) (38-51 mu M). These data suggest that the therapeutic efficacy of some antipsychotics may be due in part to an ability to inhibit viral replication. Antiviral agents may prove to be effective adjuncts in the treatment of schizophrenia. C1 IIT,RES INST,DEPT LIFE SCI,CHICAGO,IL 60616. NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,TWIN STUDIES UNIT,WASHINGTON,DC 20032. RP JonesBrando, LV (reprint author), JOHNS HOPKINS UNIV,STANLEY LAB STUDY SCHIZOPHRENIA & BIPOLAR DIS,DEPT PEDIAT,720 RUTLAND AVE,BALTIMORE,MD 21205, USA. NR 39 TC 24 Z9 24 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY 3 PY 1997 VL 25 IS 1 BP 63 EP 70 DI 10.1016/S0920-9964(97)00007-8 PG 8 WC Psychiatry SC Psychiatry GA WZ796 UT WOS:A1997WZ79600007 PM 9176928 ER PT J AU Jacob, L Somasundaram, R Smith, W Monos, D Basak, S Marincola, F Pereira, S Herlyn, D AF Jacob, L Somasundaram, R Smith, W Monos, D Basak, S Marincola, F Pereira, S Herlyn, D TI Cytotoxic T-cell clone against rectal carcinoma induced by stimulation of a patient's peripheral blood mononuclear cells with autologous cultured tumor cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID INFILTRATING LYMPHOCYTES; HUMAN-MELANOMA; MONOCLONAL-ANTIBODIES; COLORECTAL-CARCINOMA; METASTATIC MELANOMA; SIGNAL-TRANSDUCTION; COLON-CARCINOMA; HLA-A; ANTIGEN; EXPRESSION AB In an effort to establish cytolytic T lymphocytes (CTLs) against colorectal carcinoma (CRC) by stimulating patients' lymphocytes with autologous tumor cells, we used peripheral brood mononuclear cells (PBMC) from a patient with minimal residual rectal carcinoma following removal of the primary lesion and involved regional lymph nodes as a source to generate CTLs in culture. A CTL line and clone were established from the patient's PBMC following stimulation of PBMC with autologous, cultured tumor cells and interleukin-2. The CTL line and the clone consisted predominantly of CD4(+) lymphocytes. The CTL clone expressed two T-cell receptor variable alpha chains (V alpha 11 and V alpha 22) and one beta chain (V beta 14). The cytokine secretion pattern of the CTL line was of the Th1-type. Both the CTL line and the clone lysed the autologous rectal carcinoma cells, but not the allogeneic, partially human lymphocyte antigen (HLA)-matched or nonmatched CRC cells, autologous Epstein-Barr virus-transformed B cells, K562 (natural killer target) cells or Daudi (lymphokine-activated killer target) cells. Lysis of autologous tumor cells most likely was HLA class I-restricted. Our unique success in generating CTLs against this tumor type may rest in the inclusion of a patient with minimal residual, rather than advanced, disease. (C) 1997 Wiley-Liss, Inc. C1 WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. RIDDLE MEM HOSP,MEDIA,PA. HOSP UNIV PENN,PHILADELPHIA,PA 19104. NCI,BETHESDA,MD 20892. FU NCI NIH HHS [CA-10815] NR 40 TC 20 Z9 20 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 2 PY 1997 VL 71 IS 3 BP 325 EP 332 DI 10.1002/(SICI)1097-0215(19970502)71:3<325::AID-IJC3>3.0.CO;2-# PG 8 WC Oncology SC Oncology GA WW911 UT WOS:A1997WW91100003 PM 9139862 ER PT J AU Weiderpass, E Gridley, G Persson, I Nyren, O Ekbom, A Adami, HO AF Weiderpass, E Gridley, G Persson, I Nyren, O Ekbom, A Adami, HO TI Risk of endometrial and breast cancer in patients with diabetes mellitus SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID INSULIN; WOMEN AB Diabetes mellitus patients have metabolic and endocrine alterations that could contribute to an increased incidence of hormone-related cancers. We assessed the incidence of endometrial and breast cancer among 80,005 women and the incidence of breast cancer among 73,847 men (total of 153,852 patients) identified in the Swedish In-patient Register as having been hospitalized for diabetes mellitus in the period 1965-1983. These patients underwent follow-up through 1989 via the Swedish Cancer Register and other nation-wide Swedish registers. The outcome measures were standardized incidence ratios (SIR) based on age-, sex- and calendar period-specific incidence rates from the entire Swedish population. To minimise the effect of selection bias, we excluded from the calculation of incidence ratios the first year of observation and cases diagnosed incidentally at autopsy. Only first cancers were considered for the estimates. A total of 328 endometrial cancers (SIR = 1.8; 95% confidence interval [CI] 1.6-2.0), 1,145 female breast cancers (SIR = 1.3; 95% CI = 1.2-1.4) and 13 male breast cancers (SIR = 2.0; 95% CI = 1.0-3.4) were observed. We conclude that compared with the general population, patients with diabetes mellitus have an increased incidence of endometrial and breast cancers. (C) 1997 Wiley-Liss, Inc. C1 NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. RP Weiderpass, E (reprint author), UNIV UPPSALA HOSP,DEPT CANC EPIDEMIOL,S-75185 UPPSALA,SWEDEN. RI Weiderpass, Elisabete/M-4029-2016 OI Weiderpass, Elisabete/0000-0003-2237-0128 FU NCI NIH HHS [1-CP-85636-05] NR 21 TC 126 Z9 134 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 2 PY 1997 VL 71 IS 3 BP 360 EP 363 DI 10.1002/(SICI)1097-0215(19970502)71:3<360::AID-IJC9>3.0.CO;2-W PG 4 WC Oncology SC Oncology GA WW911 UT WOS:A1997WW91100009 PM 9139868 ER PT J AU Asgari, K Sesterhenn, IA McLeod, DG Cowan, K Moul, JW Seth, P Srivastava, S AF Asgari, K Sesterhenn, IA McLeod, DG Cowan, K Moul, JW Seth, P Srivastava, S TI Inhibition of the growth of pre-established subcutaneous tumor nodules of human prostate cancer cells by single injection of the recombinant adenovirus p53 expression vector SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID WILD-TYPE P53; GENE-TRANSFER; SUPPRESSOR GENE; ANGIOGENESIS; MUTATIONS; APOPTOSIS; INDUCTION; CARCINOMA; THERAPY; HEAD AB We have previously described potent growth-inhibitory effect of a recombinant adenovirus expressing wild type p53 (AdWTp53) in metastatic prostate cancer cells via activation of cellular p53 pathways. We have extended these observations to analyze the effects of AdWTp53 on primary cultures of radical prostatectomy specimens (RPS) and have also evaluated the gene therapeutic potential of the AdWTp53 in a nude mice model. Infection of primary cultures of prostate cancer specimens resulted in about 80% cell growth inhibition in comparison with cultures treated with control adenovirus d1312. Single injection of AdWTp53 into pre-established tumor nodules of DU145 prostate cancer cells suppressed tumor growth significantly (p = 0.0407) as determined by comparison of tumor volumes of the AdWTp53-treated vs. control vector (d1312) or PBS-treated groups. Moreover, there was no significant difference in tumor growth inhibition between single vs. multiple injections of AdWTp53. Our observations support the potential of AdWTp53 for gene therapy of prostate cancer. (C) 1997 Wiley-Liss, Inc. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT SURG,CTR PROSTATE DIS RES,BETHESDA,MD 20814. WALTER REED ARMY MED CTR,UROL SERV,WASHINGTON,DC 20307. ARMED FORCES INST PATHOL,WASHINGTON,DC 20306. NCI,MED BREAST SECT,MED BRANCH,NIH,BETHESDA,MD 20892. NR 28 TC 41 Z9 41 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 2 PY 1997 VL 71 IS 3 BP 377 EP 382 DI 10.1002/(SICI)1097-0215(19970502)71:3<377::AID-IJC13>3.0.CO;2-D PG 6 WC Oncology SC Oncology GA WW911 UT WOS:A1997WW91100013 PM 9139872 ER PT J AU Song, SY Nomizu, M Yamada, Y Kleinman, HK AF Song, SY Nomizu, M Yamada, Y Kleinman, HK TI Liver metastasis formation by laminin-1 peptide (LQVQLSIR)-adhesion selected B16-F10 melanoma cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID AMINO-ACID-SEQUENCE; TUMOR-GROWTH; BASEMENT-MEMBRANE; MESSENGER-RNA; A-CHAIN; IDENTIFICATION; ATTACHMENT; ADHESION; BINDING; COLLAGENASE AB Laminin-1, a major basement membrane glycoprotein, promotes tumor cell malignancy. Incubation of B16-F10 melanoma cells with a peptide containing an active sequence in laminin-1, designated AG-73 (leu-glu-val-glu-leu-ser-ile-arg; LQVQLSIR), enhances in vitro adhesion, migration, invasion and gelatinase production and in vivo lung colonization and metastases to the liver. In the current study, we have tried to define the mechanism of enhancement of liver metastases induced by AG-73 using B16-F10 murine melanoma cells selected for adhesion on AG-73-coated dishes. Cells were sequentially selected for adhesion more than 30 times and then characterized. AG-73 selected cells had much longer cytoplasmic processes and occasionally formed nodular aggregates. AG-73 selected cells attached 1.2- to 1.5-fold better to both AG-73 and laminin-1, were able to invade through the Matrigel-coated filter up to 6-fold more, grew s.c. 1.5-2 times faster, produced twice the number of lung colonies, and showed more liver nodules (12 of 28 vs. 1 of 27) than parental cells. Our data demonstrate that the enhanced malignant phenotype of B16-F10 cells can be observed in the absence of added peptide with the adhesion-selected cells. (C) 1997 Wiley-Liss, Inc.dagger. C1 NIDR,NIH,BETHESDA,MD 20892. NR 26 TC 41 Z9 41 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 2 PY 1997 VL 71 IS 3 BP 436 EP 441 DI 10.1002/(SICI)1097-0215(19970502)71:3<436::AID-IJC22>3.0.CO;2-C PG 6 WC Oncology SC Oncology GA WW911 UT WOS:A1997WW91100022 PM 9139881 ER PT J AU Gong, XQ Gong, WH Kuhns, DB BenBaruch, A Howard, OMZ Wang, JM AF Gong, XQ Gong, WH Kuhns, DB BenBaruch, A Howard, OMZ Wang, JM TI Monocyte chemotactic protein-2 (MCP-2) uses CCR1 and CCR2B as its functional receptors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MULTIPLE LEUKOCYTE RECEPTORS; MOLECULAR-CLONING; CHEMOKINE; EXPRESSION; RANTES; IDENTIFICATION; INTERLEUKIN-8; TRANSDUCTION; MIGRATION; CYTOKINES AB Monocyte chemotactic protein (MCP)-2 is a member of the C-C chemokine subfamily, which shares more than 60% sequence homology with MCP-1 and MCP-8 and about 30% homology with macrophage inflammatory protein (MIP)-1 alpha, regulated on activation of normal T cell expressed (RANTES), and MIP-1 beta. Despite this considerable sequence homology to other C-C chemokines, MCP-2 appears to have unique functional properties in comparison with other C-C chemokines such as MCP-1 and MCP-3. Although evidence obtained from studies on leukocytes suggested that MCP-2 may share the receptors with these C-C chemokines, the actual functional receptors for MCP-2 have not yet been identified. In this study, by using radioiodinated MCP-2, we identified high affinity binding sites for MCP-2 on human peripheral blood monocytes. The MCP-2 binding was competed for by MCP-1 and MCP-3, but less well by MIP-1 alpha or RANTES. In experiments using cells transfected with C-C chemokine receptors, I-125-MCP-2 bound to human embryonic kidney 293 cells transfected with CCR1 or CCR2B, known to also bind MIP-1 alpha/RANTES and MCP-1, respectively, but both shared by MCP-3. The binding of I-125-MCP-2 to these receptor-transfected cells was displaced completely by chemokines that bind to these receptors. Both CCR1- and CCR2B-transfected 293 cells showed significant migration in response to MCP-2, in addition to responding to other specific chemokines. These results clearly demonstrate that MCP-2, unlike MCP-1, uses both CCR1 as well as CCR2B as its functional receptors, and this accounts for the unique activities of MCP-2. C1 NCI,IRSP,SAIC FREDERICK,FCRDC,FREDERICK,MD 21702. NCI,CLIN IMMUNOL SERV,SAIC FREDERICK,FCRDC,FREDERICK,MD 21702. NCI,MOL IMMUNOREGULAT LAB,DIV BASIC SCI,FCRDC,FREDERICK,MD 21702. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 NR 26 TC 90 Z9 92 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 2 PY 1997 VL 272 IS 18 BP 11682 EP 11685 DI 10.1074/jbc.272.18.11682 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WX569 UT WOS:A1997WX56900004 PM 9115216 ER PT J AU Zamudio, FZ Conde, R Arevalo, C Becerril, B Martin, BM Valdivia, HH Possani, LD AF Zamudio, FZ Conde, R Arevalo, C Becerril, B Martin, BM Valdivia, HH Possani, LD TI The mechanism of inhibition of ryanodine receptor channels by Imperatoxin I, a heterodimeric protein from the scorpion Pandinus imperator SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CALCIUM RELEASE CHANNEL; SKELETAL-MUSCLE; SARCOPLASMIC-RETICULUM; VENOM; PEPTIDE; TOXINS; PROBE; PHOSPHOLIPASE-A(2); PURIFICATION; NEUROTOXINS AB We present an in-depth analysis of the structural and functional properties of Imperatoxin I (IpTx(1)), an similar to 15-kDa protein from the venom of the scorpion Pandinas imperator that inhibits Ca2+ release channel/ryanodine receptor (RyR) activity (Valdivia, H. H., Kirby, M. S., Lederer, W. J., and Coronado, R. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 12185-12189). A cDNA library was prepared from the venomous glands of this scorpion and used to clone the gene encoding IpTx(i). From a single continuous messenger RNA, the information coding for the toxin is translated into two mature polypeptide subunits after elimination of a basic pentapeptide. The IpTx(i) dimer consists of a large subunit (104-amino acid residues) with phospholipase A(2) (PLA(2)) activity covalently linked by a disulfide bond to a smaller (27 amino acid residues), structurally unrelated subunit, Thus, IpTx(i) is a heterodimeric protein with lipolytic action, a property that is only shared with beta-bungarotoxins, a group of neurotoxins from snake venoms. The enzymatic subunit of IpTx(i) is highly homologous to PLA(2) from bee (Apis mellifera) and lizard (Heloderma horridum) venoms, The small subunit has no significant similarity to any other known peptide, including members of the Kunitz protease inhibitors superfamily that target the lipolytic effect of beta-bungarotoxins, A synthetic peptide with amino acid sequence identical to that of the small subunit failed to inhibit RyR. On the other hand, treatment of IpTx(i) with p-bromophenacylbromide, a specific inhibitor of PLA(2) activity, greatly reduced the capacity of IpTx(i) to inhibit RyRs. These results suggested that a lipid product of PLA(2) activity, more than a direct IpTx(i)-RyR interaction, was responsible for RyR inhibition. C1 UNIV WISCONSIN,SCH MED,DEPT PHYSIOL,MADISON,WI 53706. NATL AUTONOMOUS UNIV MEXICO,INST BIOTECHNOL,DEPT MOL RECOGNIT & STRUCT BIOL,CUERNAVACA 62271,MORELOS,MEXICO. NIMH,UNIT MOL STRUCT,BETHESDA,MD 20892. RI Possani, Lourival/J-2397-2013; OI Conde, Renaud/0000-0001-9928-8937 NR 33 TC 76 Z9 77 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 2 PY 1997 VL 272 IS 18 BP 11886 EP 11894 DI 10.1074/jbc.272.18.11886 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WX569 UT WOS:A1997WX56900037 PM 9115249 ER PT J AU Gaetano, C Matsuo, T Thiele, CJ AF Gaetano, C Matsuo, T Thiele, CJ TI Identification and characterization of a retinoic acid-regulated human homologue of the unc-33-like phosphoprotein gene (hUlip) from neuroblastoma cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN NEURO-BLASTOMA; NERVE GROWTH-FACTOR; EXPRESSION; DIFFERENTIATION; LINES; RECEPTORS; INDUCTION; OUTGROWTH; SURVIVAL; CULTURE AB A cDNA, 7G1, was isolated from retinoic acid (RA) differentiated neuroblastoma cells whose expression was high in human fetal brain and spinal cord mRNA but undetectable in adult brain or non-neuronal tissues. Sequence analysis indicates that 7G1 is homologous to the Caenorhabditis elegans gene unc-33. A 5.5-kilobase pair full-length cDNA from a human fetal brain cDNA library contains an 1710-base pair open reading frame. Because the predicted 570 amino acid sequence of 7G1 shares 98% identity with the murine Ulip gene product, an unc-33-like-phosphoprotein, we refer to 7G1 as the human Ulip (hUlip). hUlip is also similar to the bacterial enzyme D-hydantoinase and the recently described vertebrate gene products CRMP62, TOAD-64, CRMP1, CRMP2, and mUNC. RA stimulates an increase in hUlip mRNA that is transcriptionally regulated. RA stimulates an increase in polypeptides of 58, 60, 65, and 70 kDa with the 58- and 65-kDa species being dephosphorylated forms of the 60- and 70-kDa species. This study presents a model in which to study the regulation and expression of the hUlip gene, a member of an emerging family of molecules that potentially mediates signals involved in axonal outgrowth. C1 NCI,CELL & MOL BIOL SECT,PEDIAT ONCOL BRANCH,NIH,BETHESDA,MD 20892. OI Gaetano, Carlo/0000-0002-5238-1832 NR 31 TC 52 Z9 54 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 2 PY 1997 VL 272 IS 18 BP 12195 EP 12201 DI 10.1074/jbc.272.18.12195 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WX569 UT WOS:A1997WX56900081 PM 9115293 ER PT J AU Melillo, G Taylor, LS Brooks, A Musso, T Cox, GW Varesio, L AF Melillo, G Taylor, LS Brooks, A Musso, T Cox, GW Varesio, L TI Functional requirement of the hypoxia-responsive element in the activation of the inducible nitric oxide synthase promoter by the iron chelator desferrioxamine SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING ACTIVITY; PICOLINIC-ACID; ERYTHROPOIETIN GENE; INTERFERON-GAMMA; MURINE MACROPHAGES; MOUSE MACROPHAGES; MAMMALIAN-CELLS; QUINOLINIC ACID; BONE-MARROW; FACTOR-I AB We have previously reported that a 19-base pair element of the 5'-flanking region of the inducible nitric oxide synthase (iNOS) gene containing a sequence homology to a hypoxia-responsive enhancer (iNOS-HRE) mediates picolinic acid (PA)- or hypoxia-induced activation of the iNOS promoter in interferon-gamma (IFN-gamma)-treated murine macrophages. The iron chelator desferrioxamine (DFX) induces the activity of the human erythropoietin enhancer in Hep3B cells. We have investigated the influence of DFX on the activation of the iNOS promoter and iNOS gene expression in ANA-1 macrophages. We have found that DFX induced DNA-binding activity to the hypoxia-inducible factor 1 (HIF-1) consensus sequence of the iNOS promoter and activated the iNOS-HRE in murine macrophages. These activities of DFX were associated with a synergistic induction of iNOS mRNA expression and iNOS transcription in IFN-gamma-treated ANA-1 macrophages. Functional analysis of the 5'-flanking region of the iNOS gene demonstrated that IFN-gamma plus DFX activated the full-length iNOS promoter and that the iNOS-HRE was required for DFX-induced iNOS transcriptional activity. We also investigated the role of iron metabolism in the DFX- or PA dependent induction of HIF-1 activity and iNOS expression, We demonstrate that addition of iron sulfate completely abolished DFX or PA induction of HIF-1 binding and iNOS-HRE activation and abrogated IFN-gamma plus either DFX- or PA-induced iNOS expression. These data establish that DFX is a co-stimulus for the transcriptional activation of the iNOS gene in IFN-gamma-treated macrophages, and they provide evidence that the iNOS-HRE is required for the DFX-dependent activation of the iNOS promoter. Furthermore, our results indicate that the iNOS-HRE is a regulatory element of the iNOS pro meter responsive to iron chelation. C1 NCI,INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,FREDERICK CANC RES & DEV CTR,NIH,FREDERICK,MD 21702. NCI,EXPT IMMUNOL LAB,DIV BASIC SCI,FREDERICK CANC RES & DEV CTR,NIH,FREDERICK,MD 21702. RI varesio, luigi/J-8261-2016 OI varesio, luigi/0000-0001-5659-2218 FU Telethon [A.075] NR 50 TC 156 Z9 160 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 2 PY 1997 VL 272 IS 18 BP 12236 EP 12243 DI 10.1074/jbc.272.18.12236 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WX569 UT WOS:A1997WX56900087 PM 9115299 ER PT J AU Zdanov, A SchalkHihi, C Menon, S Moore, KW Wlodawer, A AF Zdanov, A SchalkHihi, C Menon, S Moore, KW Wlodawer, A TI Crystal structure of Epstein-Barr virus protein BCRF1, a homolog of cellular interleukin-10 SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE cytokines; interleukins; receptor binding; crystal structure; viral proteins ID INTERFERON-GAMMA; CYTOKINE PRODUCTION; RECEPTOR; REFINEMENT; EXPRESSION; HORMONE; COMPLEX; CLONES; IL-10; GENE AB The crystal structure of Epstein-Barr virus protein BCRF1, an analog of cellular interleukin-10 (IL-10), has been determined at the resolution of 1.9 Angstrom and refined to an R-factor 0.191. The structure of this cytokine is similar to that of human IL-10 (hIL-10), forming an intercalated dimer of two 17 kDa polypeptides related by a crystallographic 2-fold symmetry axis. BCRF1 exhibits novel conformations of the N-terminal coil and of the loop between helices A and B compared to hIL-10. These regions are likely to be involved in binding of one or more components of the IL-10 receptor system, and thus the structural differences may account for the lower binding affinity and limited spectrum of biological activities of viral IL-10, compared to hIL-10. (C) 1997 Academic Press Limited. C1 NCI,MACROMOL STRUCT LAB,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,FREDERICK,MD 21702. DNAX RES INST MOL & CELLULAR BIOL INC,DEPT MOL BIOL,PALO ALTO,CA 94304. NR 27 TC 66 Z9 71 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 MAY 2 PY 1997 VL 268 IS 2 BP 460 EP 467 DI 10.1006/jmbi.1997.0990 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WX564 UT WOS:A1997WX56400019 PM 9159483 ER PT J AU Pozsgay, V Dubois, EP Pannell, L AF Pozsgay, V Dubois, EP Pannell, L TI Synthesis of kojidextrins and their protein conjugates. Incidence of steric mismatch in oligosaccharide synthesis SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI K-12; CAPSULAR POLYSACCHARIDE; NMR-SPECTROSCOPY; D-GLUCOSE; GLYCOSIDES; DISACCHARIDES; TRISACCHARIDE; FRAGMENT; REAGENT; DERIVATIVES AB Kojidextrins are biologically important oligosaccharides that are involved in many physiological processes including protein glycosylation and bacterial growth. As part of our project to explore the role kojidextrins may play in bacterial pathogenesis, here we report Synthetic routes to kojibiose (54), -triose (58), -tetraose (64), and -pentaose (69) equipped with alpha-linked (hydrazinocarbonyl)-pentyl aglycon, using linear and convergent strategies. In the search for a rapid convergent strategy for the construction of extended kojidextrins, four kojibiose donors (1-4) were synthesized that contain acyl- and ether-type protecting groups in various ratios. These were tested to probe the influence of diverse protecting group assemblies on their glycosyl donor ability. Attempted condensation of these donors with kojitriose and -tetraose accepters failed to give the desired products apparently because of steric mismatch between the donor and the acceptor moieties. A one-pot procedure was developed for the covalent attachment of the synthetic saccharides through their hydrazido group to human serum albumin (HSA) using Tietze's squarate method to give neoglycoproteins containing up to 28 saccharide units per HSA. C1 NIDDKD,DEPT BIOORGAN CHEM,NIH,BETHESDA,MD 20892. RP Pozsgay, V (reprint author), NICHHD,DEV & MOL IMMUN LAB,NIH,BETHESDA,MD 20892, USA. NR 61 TC 40 Z9 41 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD MAY 2 PY 1997 VL 62 IS 9 BP 2832 EP 2846 DI 10.1021/jo962300y PG 15 WC Chemistry, Organic SC Chemistry GA WX159 UT WOS:A1997WX15900025 ER PT J AU Gomez, AM Valdivia, HH Cheng, H Lederer, MR Santana, LF Cannell, MB McCune, SA Altschuld, RA Lederer, WJ AF Gomez, AM Valdivia, HH Cheng, H Lederer, MR Santana, LF Cannell, MB McCune, SA Altschuld, RA Lederer, WJ TI Defective excitation-contraction coupling in experimental cardiac hypertrophy and heart failure SO SCIENCE LA English DT Article ID RAT VENTRICULAR MYOCYTES; BETA-ADRENERGIC STIMULATION; SALT-RESISTANT RATS; SARCOPLASMIC-RETICULUM; CALCIUM-RELEASE; GUINEA-PIG; RYANODINE RECEPTORS; PURKINJE-CELL; MUSCLE CELLS; PHOSPHOLAMBAN PHOSPHORYLATION AB Cardiac hypertrophy and heart failure caused by high blood pressure were studied in single myocytes taken from hypertensive rats (Dahl SS/Jr) and SH-HF rats in heart failure. Confocal microscopy and patch-clamp methods were used to examine excitation-contraction (EC) coupling, and the relation between the plasma membrane calcium current (I-Ca) and evoked calcium release from the sarcoplasmic reticulum (SR), which was visualized as ''calcium sparks.'' The ability of I-Ca to trigger calcium release from the SR in both hypertrophied and failing hearts was reduced. Because I-Ca density and SR calcium-release channels were normal, the defect appears to reside in a change in the relation between SR calcium-release channels and sarcolemmal calcium channels. beta-Adrenergic stimulation largely overcame the defect in hypertrophic but not failing heart cells. Thus, the same defect in EC coupling that develops during hypertrophy may contribute to heart failure when compensatory mechanisms fail. C1 UNIV MARYLAND,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,CTR MED BIOTECHNOL,BALTIMORE,MD 21201. UNIV WISCONSIN,SCH MED,DEPT PHYSIOL,MADISON,WI 53706. NIA,SECT CARDIOVASC RES,BALTIMORE,MD 21224. UNIV LONDON ST GEORGES HOSP,SCH MED,DEPT PHARMACOL & CLIN PHARMACOL,LONDON SW17 0RE,ENGLAND. OHIO STATE UNIV,DEPT FOOD SCI & TECHNOL,COLUMBUS,OH 43210. OHIO STATE UNIV,DEPT MED BIOCHEM,COLUMBUS,OH 43210. RI Lederer, William/B-1285-2010; Gomez, Ana Maria/B-5376-2013; OI Gomez, Ana Maria/0000-0003-0009-2884; Santana, Luis/0000-0002-4297-8029 FU Wellcome Trust NR 75 TC 560 Z9 571 U1 1 U2 21 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAY 2 PY 1997 VL 276 IS 5313 BP 800 EP 806 DI 10.1126/science.276.5313.800 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WW900 UT WOS:A1997WW90000060 PM 9115206 ER PT J AU Heishman, SJ Balfour, DJK Benowitz, NL Hatsukami, DK Lindstrom, JM Ockene, JK AF Heishman, SJ Balfour, DJK Benowitz, NL Hatsukami, DK Lindstrom, JM Ockene, JK TI Society for research on nicotine and tobacco SO ADDICTION LA English DT Editorial Material ID SMOKING CESSATION; CIGARETTE-SMOKING; NASAL SPRAY; RECEPTOR; THERAPY; REPLACEMENT; DOPAMINE AB The proceedings of the second annual scientific conference of the Society for Research on Nicotine and Tobacco are summarized. The goal of the annual conference was to disseminate information about ongoing nicotine research from biological, behavioral and social perspectives. Data were presented describing our current understanding of the structure and function of neuronal nicotinic acetylcholine receptors, by which nicotine exerts most, if not all, of its effects in the brain. The conformational complexity of receptor subunits expressed in different brain areas contributes significantly to the complexity of responses observed to nicotinic agonists. Nicotine is being developed as a medication that might be used to maintain smoking cessation and to treat various medical diseases. The potential toxicity of nicotine, apart from cigarette smoking, is an important variable in assessing the benefits and risks of such therapeutic applications. The risks of nicotine-containing medications appear to be far less than those associated with tobacco use. Recent data indicate that cigarette smoking is increasing among youth in the United States. Adolescent smokers are interested in quitting and make frequent quit attempts, but are usually nor successful. Effective methods are needed to manage adolescent smokers before they become heavily addicted. Nicotine replacement as a pharmacological treatment for smoking cessation has made a significant contribution in improving quit rates. New medications have been developed that target specific populations of smokers. C1 UNIV DUNDEE, SCH MED, INST NEUROSCI, DUNDEE DD1 4HN, SCOTLAND. UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA 94143 USA. UNIV MINNESOTA, MINNEAPOLIS, MN USA. UNIV PENN, SCH MED, PHILADELPHIA, PA 19104 USA. UNIV MASSACHUSETTS, SCH MED, WORCESTER, MA USA. RP Heishman, SJ (reprint author), NIDA, ADDICT RES CTR, CLIN PHARMACOL BRANCH, INTRAMURAL RES PROGRAM, 5500 NATHAN SHOCK DR, BALTIMORE, MD 21224 USA. NR 42 TC 5 Z9 5 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0965-2140 J9 ADDICTION JI Addiction PD MAY PY 1997 VL 92 IS 5 BP 615 EP 623 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA WZ730 UT WOS:A1997WZ73000019 PM 9219386 ER PT J AU Bell, SL Singleton, EG Heishman, SJ Henningfield, JE AF Bell, SL Singleton, EG Heishman, SJ Henningfield, JE TI Effects of smoking and deprivation on craving and human performance SO ADDICTION LA English DT Meeting Abstract C1 NIDA,INTRAMURAL RES PROGRAM,BALTIMORE,MD. NR 0 TC 0 Z9 0 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 MAY PY 1997 VL 92 IS 5 BP 623 EP 623 PG 1 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA WZ730 UT WOS:A1997WZ73000020 ER PT J AU Pickworth, WB Fant, RV Gnjidic, M Stanton, JP AF Pickworth, WB Fant, RV Gnjidic, M Stanton, JP TI Delayed auditory feedback (DAF) during tobacco withdrawal SO ADDICTION LA English DT Meeting Abstract C1 NIDA,ADDICT RES CTR,NIH,BALTIMORE,MD 21224. COLL NOTRE DAME MARYLAND,BALTIMORE,MD. NR 0 TC 0 Z9 0 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 MAY PY 1997 VL 92 IS 5 BP 628 EP 628 PG 1 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA WZ730 UT WOS:A1997WZ73000042 ER PT J AU Shoaib, M Swanner, LS Schindler, CW Goldberg, SR AF Shoaib, M Swanner, LS Schindler, CW Goldberg, SR TI Genetic and environmental factors in nicotine self-administration SO ADDICTION LA English DT Meeting Abstract C1 NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 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 MAY PY 1997 VL 92 IS 5 BP 631 EP 631 PG 1 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA WZ730 UT WOS:A1997WZ73000051 ER PT J AU Pearson, JL Conwell, Y Lindesay, J Takahashi, Y Caine, ED AF Pearson, JL Conwell, Y Lindesay, J Takahashi, Y Caine, ED TI Elderly suicide: a multi-national view SO AGING & MENTAL HEALTH LA English DT Review ID COMPLETED SUICIDE; DEPRESSION; AGE; RATES; INPATIENTS; MANAGEMENT; SYMPTOMS; CARE AB Males age 75 and older have the highest rates of suicide in nearly all industrialized countries. A fairly consistent pattern of risk factors for elderly suicides, in contrast to younger victims, includes major depression diagnoses without comorbid substance use, and comorbid physical illness. Older suicides also demonstrate greater lethality of self-destructive behaviors compared to younger groups. With regard to service use, reports from the US, UK and Japan find that most of the elderly suicides have contact with a primary health care provider in the month prior to the suicide. Altogether, these findings suggest means for primary and secondary prevention efforts. This paper summarizes research findings and recent prevention efforts from several nations. C1 UNIV ROCHESTER,DEPT PSYCHIAT,ROCHESTER,NY 14627. UNIV LEICESTER,LEICESTER GEN HOSP,LEICESTER,LEICS,ENGLAND. TOKYO INST PSYCHIAT,TOKYO,JAPAN. RP Pearson, JL (reprint author), NIMH,RM 18-101,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 53 TC 14 Z9 15 U1 3 U2 5 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 1360-7863 J9 AGING MENT HEALTH JI Aging Ment. Health PD MAY PY 1997 VL 1 IS 2 BP 107 EP 111 PG 5 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA YJ967 UT WOS:A1997YJ96700001 ER PT J AU Wagner, AW Logsdon, RG Pearson, JL Teri, L AF Wagner, AW Logsdon, RG Pearson, JL Teri, L TI Caregiver expressed emotion and depression in Alzheimer's disease SO AGING & MENTAL HEALTH LA English DT Article ID PSYCHIATRIC-PATIENTS; AFFECTIVE-DISORDERS; FUNCTIONAL STATUS; FAMILY; DEMENTIA; SCHIZOPHRENIA; RELATIVES; BURDEN; RELIABILITY; IMPAIRMENT AB Expressed Emotion (EE) has been a useful construct for understanding the relationship between family interactions and depression in patients with psychiatric disorders. It has not, however, been well studied in patients with Alzheimer's disease (AD) and their caregivers despite its potential utility in clarifying patient-caregiver interactions and how such interactions may affect patient function, and caregiver burden, mood and quality of care. This study investigated the rate of EE in caregivers of patients with AD and depression. It also investigated the relationship of caregiver EE to patient status and caregiver burden and depression. Fifty-seven AD patient-caregiver dyads were studied in a cross-sectional design. Caregiver measures included the EE Speech Sample, Burden Inventory, and Center for Epidemiological Studies-Depression Scale. Patient measures included the Hamilton Depression Rating Scale, Record of Independent Living, and Revised Memory and Behavior Problem Checklist. Twenty-three (40%) caregivers were high in EE, 34: (60%) were low. This percentage is higher than reported in normal older adults but is consistent with other psychiatric populations. High EE caregivers were significantly more likely to be clinically depressed and have higher levels of burden. They also endorsed fewer positive aspects of caregiving. No relationship was found between caregiver EE status and patient variables. Caregiver EE offers a novel approach to understanding important aspects of caregiver-patient interactions which may impact long term patient functioning and caregivers' ability to provide effective care. C1 UNIV WASHINGTON,SCH MED,DEPT PSYCHIAT & BEHAV SCI,SEATTLE,WA 98195. NIMH,ROCKVILLE,MD 20857. NR 54 TC 22 Z9 22 U1 1 U2 8 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 1360-7863 J9 AGING MENT HEALTH JI Aging Ment. Health PD MAY PY 1997 VL 1 IS 2 BP 132 EP 139 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA YJ967 UT WOS:A1997YJ96700004 ER PT J AU Drummond, JE Mounts, P Gorelick, RJ CasasFinet, JR Bosche, WJ Henderson, LE Waters, DJ Arthur, LO AF Drummond, JE Mounts, P Gorelick, RJ CasasFinet, JR Bosche, WJ Henderson, LE Waters, DJ Arthur, LO TI Wild-type and mutant HIV type 1 nucleocapsid proteins increase the proportion of long cDNA transcripts by viral reverse transcriptase SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; DNA STRAND TRANSFER; ZINC FINGERS; GENOMIC RNA; ESCHERICHIA-COLI; STEADY-STATE; GAG; ACID; RETROVIRUSES; BINDING AB HIV-1 nucleocapsid, p7, contains two retroviral zinc fingers, which are both necessary for efficient packaging of geriomic RNA and infectivity. The nucleocapsid protein is bound tightly to genomic RNA in the mature virion, In this study, the effect of p7 on polymerization of nascent cDNA by viral reverse transcriptase (RT) was examined, An 874-base RNA of HIV-1 was synthesized and used as a template in RT assays with varying concentrations of intact p7, mutants of p7 that have transposed or repeated zinc fingers, and several different peptides that represent various structural regions of p7, Results indicate that at greater than or equal to 50% saturation of p7-binding sites, with p7, there is up to a 90% reduction in total cDNA synthesis, as measured by nucleotide incorporation, However, the cDNA products that are made are almost exclusively full length, Three zinc finger mutants exhibited effects similar to those of wild-type p7, N-terminal and C-terminal halves of p7 inhibited total nucleotide incorporation, but also inhibited synthesis of long cDNA products by RT, In the absence of p7 an array of short transcripts (<200 bases) was produced by RT, These studies show that full-length p7 is necessary to increase the proportion of long cDNA transcripts produced by RT, The relative position of the two zinc fingers is not critical for this effect. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MOL MICROBIOL & IMMUNOL,BALTIMORE,MD 21205. RP Drummond, JE (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,AIDS VACCINE PROGRAM,POB B,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-5600] NR 44 TC 33 Z9 33 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY 1 PY 1997 VL 13 IS 7 BP 533 EP 543 DI 10.1089/aid.1997.13.533 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA WX133 UT WOS:A1997WX13300002 PM 9135871 ER PT J AU Purohit, V AF Purohit, V TI Introduction to the symposium SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Editorial Material DE alcohol; osteoporosis; bone ID BONE-MINERAL DENSITY; VITAMIN-D METABOLISM; GROWTH-FACTOR-I; HORMONE-GH; WOMEN; ALCOHOL; OSTEOPOROSIS; ETHANOL; CELLS; RATS AB In June 1995, the National Institute on Alcohol Abuse and Alcoholism sponsored a symposium on ''Alcohol and Osteoporosis'' at the Research Society on Alcoholism in Steamboat Springs, Colorado. The goals of the symposium were to: (a) disseminate current information on the effects of alcohol on osteoporosis, both deleterious and beneficial; (b) discuss the mechanisms, direct and indirect, by which alcohol affects bone remodeling; and (9) encourage research in the area of alcohol and osteoporosis. This report provides an introduction to the problem, as well as to the three scientific presentations. RP Purohit, V (reprint author), NIAAA,BIOMED RES BRANCH,DIV BASIC RES,NIH,BETHESDA,MD 20892, USA. NR 23 TC 10 Z9 10 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 MAY PY 1997 VL 21 IS 3 BP 383 EP 384 PG 2 WC Substance Abuse SC Substance Abuse GA WZ645 UT WOS:A1997WZ64500001 ER PT J AU Cohen, SG AF Cohen, SG TI The Jewish physician in the post Columbus era: The 15th century Spanish inquisition and expulsion revisited in 20th century Germany and Austria SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article RP Cohen, SG (reprint author), NIAID,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 12 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 MAY-JUN PY 1997 VL 18 IS 3 BP 199 EP 207 DI 10.2500/108854197778984455 PG 17 WC Allergy SC Allergy GA XE532 UT WOS:A1997XE53200014 PM 9194950 ER PT J AU King, J Wang, YH Welch, RW Dhariwal, KR ConryCantilena, C Levine, M AF King, J Wang, YH Welch, RW Dhariwal, KR ConryCantilena, C Levine, M TI Use of a new vitamin C-deficient diet in a depletion-repletion clinical trial SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE ascorbic acid; vitamin C; recommended dietary allowance; men; pharmacokinetics; depletion diet ID HEALTHY ELDERLY PEOPLE; L-ASCORBIC-ACID; ADULT MALES; YOUNG MEN; SUPPLEMENTATION; PLASMA; HUMANS; MONONUCLEAR; EXCRETION AB To conduct an inpatient study on the recommended dietary allowance (RDA) for vitamin C, we developed a unique vitamin C-deficient diet using a nutrient database and selective menus. Fourteen different menus were developed offering > 300 items with 0-2.4 mg vitamin C per serving. During the 4-6 mo volunteers were hospitalized, daily dietary vitamin C was restricted to less than or equal to 5.0 mg. The mean daily dietary vitamin C intake was < 3.9 mg for the seven study subjects. With concurrent supplementation, the diet provided greater than or equal to 85% of the RDA for 17 essential nutrients. Within 3 wk of admission the diet induced vitamin C deficiency as indicated by plasma concentrations, which decreased from 23 +/- 6.9 to 6.9 +/- 2.0 mu mol/L. Daily intake of vitamin C and five other nutrients was determined by nutrient database analyses. Mean energy, protein, and iron were 105-185% of the RDA and total and saturated fat were 32% and 10% of energy, respectively. Weight and nutritionally relevant indexes remained normal. Dietary adherence, calculated by the number of days with less than or equal to 5.0 mg vitamin C per total study days, was 88-98% per repletion dose. Computer analyses of menu selections permitted individual preferences to be met while restricting vitamin C intake to less than or equal to 5.0 mg/d. There were no complications from the diet during the depletion and repletion phases. With this diet, ascorbic acid pharmacokinetics for escalating doses could be determined in healthy volunteers. C1 NIDDK,DIABET BRANCH,MOL & CLIN NUTR SECT,NIH,BETHESDA,MD 20892. NIH,DIABET BRANCH,DEPT NUTR,BETHESDA,MD 20892. NIH,DIABET BRANCH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 36 TC 11 Z9 11 U1 0 U2 1 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAY PY 1997 VL 65 IS 5 BP 1434 EP 1440 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WW078 UT WOS:A1997WW07800010 PM 9129473 ER PT J AU Cooper, GS Sandler, DP AF Cooper, GS Sandler, DP TI Long-term effects of reproductive-age menstrual cycle patterns on peri- and postmenopausal fracture risk SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE fractures; menarche; menstrual cycle; menstruation; osteoporosis, postmenopausal ID BONE-MINERAL DENSITY; ELDERLY WOMEN; MASS; EPIDEMIOLOGY; OSTEOPOROSIS; ADOLESCENTS AB The authors examined the association between age at menarche, menstrual cycle characteristics between ages 28 and 32 years, and peri- and postmenopausal fracture risk in a cohort of 874 women who prospectively recorded menstrual cycle data for at least 5 years from their early 20s through their menopause, Fracture history was obtained with a self-administered questionnaire, The mean age of respondents at the lime the questionnaire was completed was 73 years. Wrist fracture (n = 62) risk increased with increasing age at menarche (odds ratio 3.3, 95% confidence interval 1.7-6.2) for menarche age greater than or equal to 14 years compared with 12-13 years) and increasing mean cycle length at age 28-32 (odds ratio 2.2, 95% confidence interval 1.0-4.9) for >30.5 days compared with 26.6-30.5 days). Similar results were seen in analyses of the combined wrist, hip, or vertebral fracture group (n = 92). These prospectively recorded menstrual diary data indicate that age at menarche and menstrual cycle patterns may have a long-term association with fracture risk, with effects lasting into the postmenopausal years. RP Cooper, GS (reprint author), NATL INST ENVIRONM HLTH SCI,EPIDEMIOL BRANCH A305,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Sandler, Dale/0000-0002-6776-0018 FU NCRR NIH HHS [M01-RR00064] NR 27 TC 50 Z9 51 U1 0 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAY 1 PY 1997 VL 145 IS 9 BP 804 EP 809 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WX368 UT WOS:A1997WX36800005 PM 9143210 ER PT J AU Cappuccio, FP Elliott, P Allender, PS Cutler, JA AF Cappuccio, FP Elliott, P Allender, PS Cutler, JA TI Some questions about ''epidemiologic association between dietary calcium intake and blood pressure: A meta-analysis of published data'' - Reply SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter ID KIDNEY-STONES C1 IMPERIAL COLL SCH MED ST MARYS,DEPT EPIDEMIOL & PUBL HLTH,LONDON,ENGLAND. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. RP Cappuccio, FP (reprint author), UNIV LONDON ST GEORGES HOSP,SCH MED,DEPT MED,LONDON SW17 0RE,ENGLAND. RI Cappuccio, Francesco/D-3028-2009; OI Cappuccio, Francesco Paolo/0000-0002-7842-5493 NR 14 TC 0 Z9 0 U1 0 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAY 1 PY 1997 VL 145 IS 9 BP 858 EP 859 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WX368 UT WOS:A1997WX36800013 ER PT J AU Karstadt, M Haseman, JK AF Karstadt, M Haseman, JK TI Effect of discounting certain tumor types/sites on evaluations of carcinogenicity in laboratory animals SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE chemical carcinogens; carcinogenesis; cancer; rodent bioassays; carcinogenicity testing; extrapolation of animal cancer data to humans; cancer mechanisms; classification of chemicals as carcinogens ID CHEMICALS AB It has been suggested that, for mechanistic reasons, certain tumors found in experimental animals should be discounted when evaluating carcinogenic effects. The questioned tumors are: mouse liver rat thyroid follicular cell, bladder and kidney (male rat), forestomach (mouse and rat, gavage route), and lung (mouse and rat, inhalation of particles). We sought to determine the effects of discounting those tumors on classification of chemicals as carcinogens in animals. We looked at carcinogenicity data for chemicals studied in NCI-NTP bioassays and/or reviewed in IARC monographs and we found that deleting the questioned tumors would have significant impact on evaluations of carcinogenicity in animals. Fifty-six of 234 (24%) chemicals determined to be carcinogenic in the NCI-NTP bioassay program would no longer be considered carcinogenic; 102 (44%) would have weaker evidence of carcinogenic effects. Thirty-three of 361 (9%) chemicals determined by IARC to have ''limited'' or ''sufficient'' evidence of carcinogenicity would no longer be considered carcinogenic; 119 (33%) would have weaker evidence of carcinogenic effects. Because such a large number of chemicals currently considered carcinogenic would be affected by categorical deletions of tumors and because we are not aware of data that would justify such categorical deletions, it Mould be preferable to consider mechanistic justifications for discounting tumors on a case-by-case basis for each individual chemical. Deletion of tumors public health. (C) 1997 Wiley-Liss, Inc. C1 NIEHS,RES TRIANGLE PK,NC 27709. NR 5 TC 12 Z9 12 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 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD MAY PY 1997 VL 31 IS 5 BP 485 EP 494 DI 10.1002/(SICI)1097-0274(199705)31:5<485::AID-AJIM1>3.0.CO;2-T PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WR015 UT WOS:A1997WR01500001 PM 9099349 ER PT J AU Hall, WD Kusek, JW Kirk, KA Appel, LJ Schulman, G Agodoa, LY Glassock, R Grim, C Randall, OS Massry, SG Jones, CA Striker, GE Wright, JT Smith, MC Petrulis, AS Douglas, JG Milligan, S Haynie, R Pospisil, R Olutade, BO Douglas, M Wilkening, B Butler, VH Dean, LF Cleveland, W Howard, A Levell, B Kopple, JD Peng, S Shamir, E Ching, C Miladinovich, L Afre, GM Childress, MH Cruz, I Diggs, JA Dillard, M CrawfordGreen, CG Hosten, AW Lewis, JF McDaniel, WW Mehrotra, PP Retta, T Robinson, F Webber, JD Williams, H Divagracia, L Kearse, D Brady, S Ellis, B Whelton, P Coresh, J Charleston, J Meneses, J Harris, V Creary, L Norris, K Ward, H Habra, T Miller, M Toto, RD Mitchell, HC Zeller, KR BradleyGuidry, C Campese, V Smogorzewski, M Kiefer, S Richardson, AB Breyer, JA Fogo, A Powers, SN Wilson, C Faulkner, M Green, N Woodard, T Greene, PG Lee, JY Raczynski, JM Smith, DE Debruge, J Chandra, G McLean, BE Owsley, JC Bernhard, S VanLente, F Hall, PM Rolin, HA Pexa, D Luke, R Cook, C Falkner, B Ford, C Kotchen, T Neaton, J Probstfield, J Saunders, E Secundy, M Williams, J Anzolone, D Bourgoignie, JJ Buckalew, D Cheek, D Hebert, L Olech, C Porush, JG Rostand, SG Shahinfar, S Adelstein, R AlAwqati, Q Bollander, R Schwartz, M AF Hall, WD Kusek, JW Kirk, KA Appel, LJ Schulman, G Agodoa, LY Glassock, R Grim, C Randall, OS Massry, SG Jones, CA Striker, GE Wright, JT Smith, MC Petrulis, AS Douglas, JG Milligan, S Haynie, R Pospisil, R Olutade, BO Douglas, M Wilkening, B Butler, VH Dean, LF Cleveland, W Howard, A Levell, B Kopple, JD Peng, S Shamir, E Ching, C Miladinovich, L Afre, GM Childress, MH Cruz, I Diggs, JA Dillard, M CrawfordGreen, CG Hosten, AW Lewis, JF McDaniel, WW Mehrotra, PP Retta, T Robinson, F Webber, JD Williams, H Divagracia, L Kearse, D Brady, S Ellis, B Whelton, P Coresh, J Charleston, J Meneses, J Harris, V Creary, L Norris, K Ward, H Habra, T Miller, M Toto, RD Mitchell, HC Zeller, KR BradleyGuidry, C Campese, V Smogorzewski, M Kiefer, S Richardson, AB Breyer, JA Fogo, A Powers, SN Wilson, C Faulkner, M Green, N Woodard, T Greene, PG Lee, JY Raczynski, JM Smith, DE Debruge, J Chandra, G McLean, BE Owsley, JC Bernhard, S VanLente, F Hall, PM Rolin, HA Pexa, D Luke, R Cook, C Falkner, B Ford, C Kotchen, T Neaton, J Probstfield, J Saunders, E Secundy, M Williams, J Anzolone, D Bourgoignie, JJ Buckalew, D Cheek, D Hebert, L Olech, C Porush, JG Rostand, SG Shahinfar, S Adelstein, R AlAwqati, Q Bollander, R Schwartz, M TI Short-term effects of blood pressure control and antihypertensive drug regimen on glomerular filtration rate: The African-American Study of Kidney Disease and Hypertension pilot study SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE renal function; blacks; blood pressure; hypertensive nephrosclerosis ID CONVERTING ENZYME-INHIBITORS; CHRONIC RENAL-DISEASE; CALCIUM-ANTAGONISTS; INSUFFICIENCY; PROGRESSION; NEPHROSCLEROSIS AB The African-American Study of Kidney Disease and Hypertension pilot study randomized 94 nondiabetic black men and women (mean age, 53 years; 75% male) with presumed hypertensive nephrosclerosis and a baseline glomerular filtration rate (GFR) of 25 to 70 mL/min/1.73 m(2) (mean, 52.3 mL/min/1.73 m(2)) to blood pressure control at either a low mean arterial pressure (MAP) goal of less than or equal to 92 mm Hg or a usual MAP goal of 102 to 107 mm Hg and an antihypertensive drug regimen that included either a calcium antagonist (amlodipine), a beta-blocker (atenolol), or an angiotensin-converting enzyme (ACE) inhibitor (enalapril). After 3 months of follow-up (n = 90), the mean GFR was similar (53.0 mL/min/1.73 m(2) v 53.7 mL/min/1.73 m(2)) to the baseline levels in participants randomized to the low MAP group (n = 44), whereas the mean GFR increased by 3.9 mL/min/1.73 m(2) (P = 0.02) in participants randomized to the usual MAP group (n = 46). During the same period of time, the mean GFR increased significantly in participants randomized to the calcium channel blocker regimen (n = 28) (5.7 mL/min/1.73 m(2); P = 0.01) but not in participants randomized to the beta-blocker regimen (n = 31) (1.7 mL/min/1.73 m(2); P = 0.10) or the ACE inhibitor regimen (n = 31) (-1.1 mL/min/1.73 m(2); P = 0.52). Changes in GFR at 3 months were significantly different among the three treatment groups (P = 0.04). We conclude that the magnitude of short-term effects of blood pressure control and antihypertensive drug regimens on GFR should be considered when estimating sample size for clinical trials designed to evaluate the effects of these interventions on long-term changes in GFR slope. (C) 1997 by the National Kidney Foundation, Inc. C1 NIDDKD,NIH,BETHESDA,MD 20892. FU NIDDK NIH HHS [DK45373, DK45381, DK45431] NR 38 TC 19 Z9 19 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAY PY 1997 VL 29 IS 5 BP 720 EP 728 DI 10.1016/S0272-6386(97)90125-6 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA WZ641 UT WOS:A1997WZ64100011 PM 9159306 ER PT J AU DuBose, TD Warnock, DG Mehta, RL Bonventre, JV Hammerman, MR Molitoris, BA Paller, MS Siegel, NJ Scherbenske, J Striker, GE AF DuBose, TD Warnock, DG Mehta, RL Bonventre, JV Hammerman, MR Molitoris, BA Paller, MS Siegel, NJ Scherbenske, J Striker, GE TI Acute renal failure in the 21st century: Recommendations for management and outcomes assessment SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE acute renal failure; continuous renal replacement therapy; intermittent renal replacement therapy; experimental therapies; hemodynamic monitoring; critical care unit ID CRITICALLY ILL PATIENTS; DIALYSIS; REPLACEMENT; CREATININE; THERAPY; TRIAL AB Acute renal failure (ARF) remains a common and potentially devastating disorder affecting as many of 5% of all hospitalized patients, with a higher prevalence in patients in critical care units. ARF is more frequently observed in the setting of multiorgan dysfunction syndrome (MODS) and in elderly patients with complex disease, where mortality is high. Numerous technical advances have not yet impacted favorably on this high mortality rate. This report summarizes recommendations from participants at the National Institutes of Health Conference: ''Acute Renal Failure in the 21st Century,'' May 6 to 8, 1996, in Bethesda, MD. The focus is on categorizing recent clinically relevant developments in the field and on identification of new research initiatives to transfer a new body of knowledge derived from fundamental studies and laboratory investigation to the management of ARF in the new millennium. The development of a multicenter database through cooperative multicenter studies is advocated. Future studies should define the appropriate outcome measures to assess and emphasize the impact of hemodynamic monitoring, adjunctive agents, and adequacy and modality of renal replacement therapy on outcomes in ARF. (C) 1997 by the National Kidney Foundation, Inc. C1 UNIV ALABAMA,BIRMINGHAM,AL. UNIV CALIF SAN DIEGO,SCH MED,SAN DIEGO,CA 92103. HARVARD UNIV,SCH MED,BOSTON,MA. WASHINGTON UNIV,SCH MED,ST LOUIS,MO. INDIANA UNIV,INDIANAPOLIS,IN 46204. UNIV MINNESOTA,MINNEAPOLIS,MN. YALE UNIV,SCH MED,NEW HAVEN,CT. NIDDK,DKUHD,NIH,BETHESDA,MD. RP DuBose, TD (reprint author), UNIV TEXAS,SCH MED,DIV RENAL DIS & HYPERTENS,6431 FANNIN,MSB 4136,HOUSTON,TX 77030, USA. RI Hammerman, Marc/B-9215-2008 NR 31 TC 73 Z9 78 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAY PY 1997 VL 29 IS 5 BP 793 EP 799 DI 10.1016/S0272-6386(97)90136-0 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA WZ641 UT WOS:A1997WZ64100023 PM 9159318 ER PT J AU Bottoms, SF Paul, RH Iams, JD Mercer, BM Thom, EA Roberts, JM Caritis, SN Moawad, AH VanDorsten, JP Hauth, JC Thurnau, GR Miodovnik, M Meis, PM McNellis, D AF Bottoms, SF Paul, RH Iams, JD Mercer, BM Thom, EA Roberts, JM Caritis, SN Moawad, AH VanDorsten, JP Hauth, JC Thurnau, GR Miodovnik, M Meis, PM McNellis, D TI Obstetric determinants of neonatal survival: Influence of willingness to perform cesarean delivery on survival of extremely low-birth-weight infants SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE low birth weight; perinatal mortality; cesarean birth ID CHILDREN; GRAMS; AGE; OUTCOMES; HEALTH AB OBJECTIVE: Our purpose was to evaluate the relationship between the approach to obstetric management and survival of extremely low-birth-weight infants. STUDY DESIGN: In this prospective observational study we evaluated 713 singleton births of infants weighing less than or equal to 1000 gm during I year at the 11 tertiary perinatal care centers of (t)he National institutes of Child Health and Human Development network of maternal-fetal medicine units. Major anomalies, extramural delivery, antepartum stillbirth, induced abortion, and gestational age <21 weeks were excluded. The obstetrician's opinion of viability and willingness to perform cesarean delivery in the event of fetal distress were ascertained from the medical record or interview when documentation was unclear. Grade 3 and 4 intraventricular hemorrhage, grade 3 and 4 retinopathy of prematurity, necrotizing enterocolitis requiring surgery, oxygen dependence at discharge or 120 days, and seizures were considered serious morbidity. Survival without serious morbidity was considered intact survival. Logistic regression was used to evaluate the influence of the approach to obstetric management, adjusted for birth weight, growth, gender, presentation, and ethnicity. RESULTS: Willingness to perform cesarean delivery was associated with increased likelihood of both survival (adjusted odds ratio 3.7, 95% confidence interval 2.3 to 6.0) and intact survival (adjusted odds ratio 1.8, 95% confidence interval 1.0 to 3.3). Willingness to intervene for fetal indications appeared to virtually eliminate intrapartum stillbirth and to reduce neonatal mortality. Below 800 gm or 26 weeks, however, willingness to perform cesarean delivery was linked to an increased chance of survival with serious morbidity. Although obstetricians were willing to intervene for fetal indications in most cases by 24 weeks, willingness to perform cesarean delivery was associated with twice the risk for serious morbidity at that gestational age. CONCLUSIONS: The approach to obstetric management significantly influences the outcome of extremely low-birth-weight infants. Above 800 gm or 26 weeks the obstetrician should usually be willing to perform cesarean delivery for fetal indications. Between 22 and 25 weeks willingness to intervene results in greater likelihood of both intact survival and survival with serious morbidity. In these cases patients and physicians should be aware of the impact of the approach to obstetric management and consider the likelihood of serious morbidity and mortality when formulating plans for delivery. C1 OHIO STATE UNIV HOSP,DEPT OBSTET & GYNECOL,COLUMBUS,OH 43210. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC 27103. UNIV ALABAMA,TUSCALOOSA,AL 35487. GEORGE WASHINGTON UNIV,BIOSTAT COORDINATING CTR,WASHINGTON,DC 20052. UNIV CHICAGO,CHICAGO,IL 60637. MED UNIV S CAROLINA,CHARLESTON,SC 29425. UNIV CINCINNATI,CINCINNATI,OH 45221. UNIV OKLAHOMA,NORMAN,OK 73019. NICHHD,BETHESDA,MD 20892. UNIV PITTSBURGH,MAGEE WOMENS HOSP,PITTSBURGH,PA 15260. OHIO STATE UNIV,COLUMBUS,OH 43210. UNIV SO CALIF,LOS ANGELES,CA 90089. UNIV TENNESSEE,KNOXVILLE,TN 37996. WAYNE STATE UNIV,HUTZEL HOSP,DETROIT,MI 48202. OI caritis, steve/0000-0002-2169-0712 FU NICHD NIH HHS [HD 19897, HD 21410, HD 21414] NR 16 TC 132 Z9 134 U1 1 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 MAY PY 1997 VL 176 IS 5 BP 960 EP 966 DI 10.1016/S0002-9378(97)70386-7 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XA165 UT WOS:A1997XA16500002 PM 9166152 ER PT J AU Nussenblatt, RB Gery, I Weiner, HL Ferris, FL Shiloach, J Remaley, N Perry, C Caspi, RR Hafler, DA Foster, CS Whitcup, SM AF Nussenblatt, RB Gery, I Weiner, HL Ferris, FL Shiloach, J Remaley, N Perry, C Caspi, RR Hafler, DA Foster, CS Whitcup, SM TI Treatment of uveitis by oral administration of retinal antigens: Results of a phase I/II randomized masked trial SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MYELIN BASIC-PROTEIN; COLLAGEN-INDUCED ARTHRITIS; II COLLAGEN; S-ANTIGEN; SUPPRESSION; TOLERANCE; DISEASE; UVEORETINITIS; INDUCTION AB PURPOSE: To evaluate the effect and safety of the oral administration of retinal antigens as a treatment of ocular inflammation. METHODS: In a phase I/II randomized masked trial, patients with endogenous uveitis who were dependent on immunosuppressive agents were randomly assigned to receive either retinal S antigen alone (10 patients), retinal S antigen and a mixture of soluble retinal antigens (10 patients), a mixture of soluble retinal antigens alone (10 patients), or placebo (15 patients). An attempt was then made to taper patients completely off their standard immunosuppressive therapy over an 8-week period. The primary study endpoint was time to ocular inflammatory attack. The secondary study endpoint was the ability to taper patients completely off their immunosuppressive or cytotoxic medication within 8 weeks. RESULTS: Time to development of the main study endpoint was not statistically significantly different for any of the four treatment groups. However, the group receiving the purified S antigen alone appeared to be tapered off their immuno suppressive medication more successfully compared with patients given placebo (P = .08), whereas all the other groups appeared to do worse than did those receiving placebo. No toxic effects attributable to any treatment were observed. CONCLUSIONS: This phase I/II study is the first to test the use of orally administered S antigen in the treatment of uveitis. Although not statistically significant, patients given S antigen were more likely to be tapered off their chronically administered systemic immunosuppressive therapy than were the other groups tested. C1 NEI,BIOMETRY & EPIDEMIOL BRANCH,NIH,BETHESDA,MD 20892. NIDDKD,BIOTECHNOL UNIT,CELLULAR & DEV BIOL LAB,NIH,BETHESDA,MD 20892. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. RP Nussenblatt, RB (reprint author), NEI,IMMUNOL LAB,NIH,BLDG 10,ROOM 10N-202,10 CTR DR,BETHESDA,MD 20892, USA. NR 35 TC 105 Z9 112 U1 0 U2 0 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 MAY PY 1997 VL 123 IS 5 BP 583 EP 592 PG 10 WC Ophthalmology SC Ophthalmology GA WX869 UT WOS:A1997WX86900001 PM 9152063 ER PT J AU Snow, JB AF Snow, JB TI News from the National Institute on Deafness and Other Communication Disorders SO AMERICAN JOURNAL OF OTOLOGY LA English DT News Item RP Snow, JB (reprint author), NATL INST DEAFNESS & OTHER COMMUN DISORDERS,NIH,BETHESDA,MD, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD MAY PY 1997 VL 18 IS 3 BP 285 EP 287 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA WX858 UT WOS:A1997WX85800002 PM 9149818 ER PT J AU Watanabe, M McCormick, KL Volker, K Ortaldo, JR Wigginton, JM Brunda, MJ Wiltrout, RH Fogler, WE AF Watanabe, M McCormick, KL Volker, K Ortaldo, JR Wigginton, JM Brunda, MJ Wiltrout, RH Fogler, WE TI Regulation of local host-mediated anti-tumor mechanisms by cytokines - Direct and indirect effects on leukocyte recruitment and angiogenesis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CELL-ADHESION MOLECULE-1; LEWIS-LUNG-CARCINOMA; IN-VIVO; ENDOTHELIAL CHANGES; CANCER METASTASIS; GROWTH-FACTOR; KILLER-CELLS; MICE; LYMPHOCYTES; INHIBITOR AB The regulation of tumor growth by cytokine-induced alterations in host effector cell recruitment and activation is intimately associated with leukocyte adhesion and angiogenic modulation. In the present study, we have developed a novel tumor model to investigate this complex series of events in response to cytokine administration. Gelatin sponges containing recombinant human basic fibroblast growth factor (rhFGFb) and B16F10 melanoma cells were implanted onto the serosal surface of the left lateral hepatic lobe in syngeneic C57BL/6 mice. The tumor model was characterized by progressive tumor growth initially localized within the sponge and the subsequent development of peritoneal carcinomatosis. Microscopic examination of the sponge matrix revealed well developed tumor-associated vascular structures and areas of endothelial cell activation as evidenced by leukocyte margination. Treatment of mice 3 days after sponge implantation with a therapeutic regimen consisting of pulse recombinant human interleukin-2 (rhIL-2) combined with recombinant murine interleukin-12 (rmIL-12) resulted in a marked hepatic mononuclear infiltrate and inhibition of tumor growth. In contrast to the control group, sponges from mice treated with rhIL-2/rmIL-12 demonstrated an overall lack of cellularity and vascular structure. The regimen of rhIL-2 in combination with rmIL-12 was equally effective against gelatin sponge implants of rhFGFb/B16F10 melanoma in SCID mice treated with anti-asialo-GM1 in the absence of a mononuclear infiltration, suggesting that T, B, and/or NK cells were not the principal mediators of the anti-tumor response in this tumor model. The absence of vascularity within the sponge after treatment suggests that a potential mechanism of rhIL-2/rmIL-12 anti-tumor activity is the inhibition of neovascular growth associated with the establishment of tumor lesions. This potential mechanism could be dissociated from the known activities of these two cytokines to induce the recruitment and activation of host effector cells. Moreover, this model provides a unique opportunity to study the cellular and molecular mechanism(s) underlying both tumor angiogenesis and leukocyte recruitment to metastatic lesions. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,EXPT IMMUNOL LAB,EXPT THERAPEUT SECT,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,INTRAMURAL SUPPORT RES PROGRAM,SAIC FREDERICK,FREDERICK,MD 21702. HOFFMANN LA ROCHE INC,DEPT ONCOL,NUTLEY,NJ 07110. NR 51 TC 50 Z9 51 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 MAY PY 1997 VL 150 IS 5 BP 1869 EP 1880 PG 12 WC Pathology SC Pathology GA WX141 UT WOS:A1997WX14100033 PM 9137109 ER PT J AU Westergaard, GC Suomi, SJ AF Westergaard, GC Suomi, SJ TI Capuchin monkey (Cebus apella) grips for the use of stone tools SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Article DE capuchin; hominid; precision grip; power grip; tool use ID TECHNOLOGY AB This research examined capuchin monkey (Cebus apella) grips for the use of throwing, nut-cracking, and cutting tools. We provided subjects with stones and apparatus that accommodated the use of stones as tools. Our subjects exhibited five grips, two of which the animals used when force was the primary consideration (power grips) and three of which the animals used when accuracy of sensory judgment and instrumentation was required (precision grips). We believe that the range of contexts in which capuchins use stone tools, combined with the ability of capuchins to employ both power and precision grips as part of their tool repertoire, indicate that Cebus apella can be used to identify grips that facilitated hominid lithic technology. (C) 1997 Wiley-Liss, Inc. RP Westergaard, GC (reprint author), NICHHD,ANIM CTR,COMPARAT ETHOL LAB,NIH,POB 529,POOLESVILLE,MD 20837, USA. NR 18 TC 16 Z9 16 U1 2 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PD MAY PY 1997 VL 103 IS 1 BP 131 EP 135 DI 10.1002/(SICI)1096-8644(199705)103:1<131::AID-AJPA9>3.0.CO;2-Z PG 5 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA XC531 UT WOS:A1997XC53100008 PM 9185956 ER PT J AU UnderwoodGordon, L Peters, DJ Bijur, P Fuhrer, M AF UnderwoodGordon, L Peters, DJ Bijur, P Fuhrer, M TI Roles of religiousness and spirituality in medical rehabilitation and the lives of persons with disabilities - A commentary SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Editorial Material C1 NICHHD,NATL CTR MED REHABIL RES,NIH,ROCKVILLE,MD 20852. FETZER INST,KALAMAZOO,MI. UNIV WASHINGTON,SCH MED,SEATTLE,WA. ALBERT EINSTEIN COLL MED,BRONX,NY 10467. NR 0 TC 18 Z9 19 U1 0 U2 0 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 MAY-JUN PY 1997 VL 76 IS 3 BP 255 EP 257 DI 10.1097/00002060-199705000-00021 PG 3 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA XG430 UT WOS:A1997XG43000017 PM 9207714 ER PT J AU Gabel, SA OConnell, TM Murphy, E London, RE AF Gabel, SA OConnell, TM Murphy, E London, RE TI Inhibition of glucose transport in human red blood cells by adenosine antagonists SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE erythrocytes; fluorodeoxyglucose; nuclear magnetic resonance ID HUMAN-ERYTHROCYTE; TRANSMEMBRANE EXCHANGE; MAGNETIZATION TRANSFER; SELECTIVE INVERSION; F-19-NMR; TRIFLUOROACETATE; SYSTEM; MODEL AB Previous studies have suggested that adenosine antagonists can interfere with normal glucose uptake in perfused rat heart. In the present studies, fluorine-19 nuclear magnetic resonance spectroscopy was used to study the effect of the adenosine antagonist, BW-A1433U, on the equilibrium exchange of fluorinated glucose analogs in human erythrocytes. Studies of the equilibrium exchange of both 2-fluoro-2-deoxy-D-glucose and 3-fluoro-3-deoxy-D-glucose with either one-dimensional magnetization transfer or two-dimensional exchange spectroscopy were performed, and significant inhibition was observed in all cases. From concentration-dependent studies, an inhibition constant for the equilibrium exchange measured at 37 degrees C of 24 mu M was determined. C1 NIEHS, MOL BIOPHYS LAB, RES TRIANGLE PK, NC 27709 USA. NR 28 TC 1 Z9 1 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD MAY PY 1997 VL 272 IS 5 BP C1415 EP C1419 PG 5 WC Cell Biology; Physiology SC Cell Biology; Physiology GA WZ061 UT WOS:A1997WZ06100001 PM 9176129 ER PT J AU Etgen, GJ Jensen, J Wilson, CM Hunt, DG Cushman, SW Ivy, JL AF Etgen, GJ Jensen, J Wilson, CM Hunt, DG Cushman, SW Ivy, JL TI Exercise training reverses insulin resistance in muscle by enhanced recruitment of GLUT-4 to the cell surface SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE photolabel; glucose transporter; muscle contraction ID OBESE ZUCKER RATS; GLUCOSE-TRANSPORT; SKELETAL-MUSCLE; PROTEIN-CONTENT; TRANSLOCATION; STIMULATION AB The effects of exercise training on cell surface GLUT-4 in skeletal muscle of the obese (fa/fa) Zucker rat were investigated using the impermeant glucose transporter photoaffinity reagent 2-N-4-(1-azi-2,2,2-trifluoroethyl)-benzoyl-1,3-bis-(D-mannos-4-yloxy)-2-propylamine (ATB-BMPA). In the absence of insulin, 3-O-methyl-D-glucose transport activity was no different in either fast-twitch (epitrochlearis) or slow-twitch (soleus) muscles of trained and sedentary obese rats. Likewise, basal ATB-BMPA-labeled GLUT-4 was not altered in these muscles with training. In contrast, the trained group exhibited significantly greater insulin-stimulated (2 mU/ml) glucose transport activity in epitrochlearis muscles than the sedentary group (0.53 +/- 0.03 vs. 0.18 +/- 0.03 mu mol.g(-1).10 min(-1) for trained and sedentary, respectively), which was paralleled by a significant enhancement of insulin-stimulated cell surface GLUT-4 (5.33 +/- 0.20 vs. 1.57 +/- 0.14 disintegrations min(-1).mg(-1) for trained and sedentary, respectively). Exercise training, however, did not alter insulin-stimulated glucose transport activity or cell surface GLUT-4 in soleus muscles. Finally, exercise training did not alter the ability of muscle contraction to elevate glucose transport activity or cell surface GLUT-4 in either epitrochlearis or soleus muscles of the obese rat. These results indicate that training improves insulin-stimulated glucose transport in muscle of the obese Zucker rat by increasing GLUT-4 content and by altering the normal intracellular distribution of these transporters such that they are now capable of migrating to the cell surface in response to the insulin stimulus. C1 UNIV TEXAS, DEPT KINESIOL, EXERCISE PHYSIOL & METAB LAB, AUSTIN, TX 78712 USA. NIDDKD, DIABET BRANCH, EXPT DIABET METAB & NUTR SECT, BETHESDA, MD 20892 USA. RI Jensen, Jorgen/O-2245-2013 NR 20 TC 61 Z9 61 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD MAY PY 1997 VL 272 IS 5 BP E864 EP E869 PG 6 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA WZ192 UT WOS:A1997WZ19200019 PM 9176187 ER PT J AU Li, ZH Bing, OHL Long, XL Robinson, KG Lakatta, EG AF Li, ZH Bing, OHL Long, XL Robinson, KG Lakatta, EG TI Increased cardiomyocyte apoptosis during the transition to heart failure in the spontaneously hypertensive rat SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE aging; DNA fragmentation; terminal deoxynucleotidyltransferase-mediated 2 '-deoxyuridine 5 '-triphosphate nick end labeling ID CELL-DEATH; GENE-EXPRESSION; HYPERTROPHY; FRAGMENTATION; SENESCENCE; CAPTOPRIL; STIFFNESS; FIBROSIS; P21 AB The transition from compensated hypertrophy to failure in spontaneously hypertensive rats (SHR) of advanced age is associated with a marked increase in collagen, a reduction in myocyte mass, and a reduction in maximum Ca2+-activated myofibrillar force. We hypothesized that the reduction in myocyte mass and associated functional loss may be due to increased cell death by apoptosis. To test this hypothesis, we studied hearts from failing (SHR-F) and nonfailing SHR (SHR-NF) and age-matched Wistar-Kyoto rats (WKY). In addition, hearts from SHR-F that had been treated with an angiotensin-converting enzyme inhibitor (captopril) for an average of 27 days were also studied. Apoptotic cells were quantified in cross sections of myocardium by the terminal deoxynucleotidyltransferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling technique. To identify the type of the cells undergoing apoptosis, sections were also stained for cu-sarcomeric actin. Apoptotic cells were significantly increased in the SHR-F (38.92 +/- 12.79 vs. 8.05 +/- 3.98 cells/100,000 nuclei in SHR-NF; P < 0.05 and vs. 2.21 +/- 1.4 cells/100,000 nuclei in WKY; P < 0.01). Captopril treatment of SHR-F reduced the number of apoptotic cells to the level in SHR-NF (9.17 +/- 1.53 cells/100,000 nuclei; P < 0.01 vs. SHR-F). Most apoptotic cells were of cardiac myocyte origin. There was no significant difference in Bcl-2 protein expressed by hearts among the three groups. WAF-1 mRNA levels were increased in both SHR groups vs. WKY; in SHR-F, the density of WAF-1 mRNA was higher than in SHR-NF. Thus increased numbers of apoptotic cells are present in failing SHR hearts, suggesting that apoptosis might be a mechanism involved in the reduction of myocyte mass that accompanies the transition from stable compensation to heart failure in this model. Administration of the angiotensin-converting enzyme inhibitor captopril, which ameliorates heart failure in this model, is associated with a reduction in the exaggerated apoptosis that accompanies heart failure. C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Vet Affairs Med Ctr, Dept Med, Boston, MA 02130 USA. RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, NIH, 4940 Eastern Ave,Box 13, Baltimore, MD 21224 USA. NR 36 TC 228 Z9 247 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAY PY 1997 VL 272 IS 5 BP H2313 EP H2319 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA WY638 UT WOS:A1997WY63800031 ER PT J AU Pallone, TL Kishore, BK Nielsen, S Agre, P Knepper, MA AF Pallone, TL Kishore, BK Nielsen, S Agre, P Knepper, MA TI Evidence that aquaporin-1 mediates NaCl-induced water flux across descending vasa recta SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE aquaporins; microcirculation; kidney; sodium; chloride; raffinose; urinary concentration ID RENAL INNER MEDULLA; COLLECTING DUCT; TRANSPORT; CHANNEL; CHIP; UREA; PROTEIN; GRADIENTS; KIDNEY; SODIUM AB Outer medullary descending vasa recta (OMDVR) were perfused in vitro, and volume efflux was measured by driving water movement with transmural gradients of NaCl or albumin. Consistent with mediation by water channels, p-chloromercuribenzenesulfonic acid (pCMBS) markedly inhibited volume flux induced by NaCl. Dithiothreitol reversed the inhibition. pCMBS did not significantly alter water flux induced by albumin. Osmotic water permeability (P-f) of the pCMBS-sensitive pathway of glutaraldehyde-fixed and nonfixed OMDVR was 1,102 +/- 449 and 1,257 +/- 718 mu m/s (means +/- SD), respectively. pCMBS reduced Pf to near zero, whereas diffusional water permeability in the same vessels was only slightly inhibited. Immunoreactive aquaporin-1 (AQP1) measured by enzyme-linked immunosorbent assay in collagenase-treated and untreated OMDVR was 5.2 +/- 1.0 and 4.2 +/- 0.4 fmol/mm, respectively, values that account well for the experimental P-f. We conclude that OMDVR water flux driven by NaCl gradients is most likely mediated by the AQP1 water channel and that NaCl and urea gradients drive water efflux in vivo by this route. C1 JOHNS HOPKINS UNIV, SCH MED, DEPT BIOL CHEM, BALTIMORE, MD 21205 USA. PENN STATE UNIV, MILTON S HERSHEY MED CTR, HERSHEY, PA 17033 USA. UNIV AARHUS, DEPT CELL BIOL, DK-8000 AARHUS, DENMARK. NHLBI, KIDNEY & ELECTROLYTE METAB LAB, NIH, BETHESDA, MD 20892 USA. RP Pallone, TL (reprint author), UNIV MARYLAND, SCH MED, DIV NEPHROL, 22 S GREENE ST, BALTIMORE, MD 21201 USA. FU NHLBI NIH HHS [HL-33991]; NIDDK NIH HHS [DK-42495] NR 35 TC 58 Z9 58 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAY PY 1997 VL 272 IS 5 BP F587 EP F596 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA WZ275 UT WOS:A1997WZ27500003 PM 9176368 ER PT J AU Shayakul, C Knepper, MA Smith, CP DiGiovanni Sr Hediger, MA AF Shayakul, C Knepper, MA Smith, CP DiGiovanni, SR Hediger, MA TI Segmental localization of urea transporter mRNAs in rat kidney SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE reverse transcription polymerase chain reaction; microdissection; collecting duct; Henle's loop ID MEDULLARY COLLECTING DUCT; VASOPRESSIN; CLONING; HENLE; LIMBS; LOOP AB Renal epithelia express at least two distinct urea transporter mRNAs, termed UT1 and UT2, that are derived from a single UT gene by alternative splicing. Previous immunolocalization studies using a polyclonal antibody that does not distinguish between the protein products of these two transcripts revealed that expression of urea transporter protein is restricted to inner medullary collecting ducts and descending thin limbs of Henle's loop. To identify which transcripts account for protein expression in these two structures, we carried out reverse transcription-polymerase chain reaction studies in microdissected structures using UT1- and UT2-specific primers. UT1 mRNA was detected only in the inner medullary collecting duct, consistent with its identification as the vasopressin-regulated urea transporter. In contrast, UT2-mRNA was detected in the late part of descending thin limbs of short loops of Henle and in the inner medullary part of descending thin limbs of long loops of Henle. This localization is consistent with the predicted role of UT2 in medullary urea recycling. Thus, in conjunction with foregoing physiological studies, our data indicate that these transporters play central roles in the urinary concentrating mechanism. C1 BRIGHAM & WOMENS HOSP, DIV RENAL, DEPT MED, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT BIOL CHEM & MOL PHARMACOL, BOSTON, MA 02115 USA. NHLBI, KIDNEY & ELECTROLYTE METAB LAB, NIH, BETHESDA, MD 20892 USA. FU NIDDK NIH HHS [R01-DK-46289] NR 21 TC 73 Z9 73 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAY PY 1997 VL 272 IS 5 BP F654 EP F660 PG 7 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA WZ275 UT WOS:A1997WZ27500012 PM 9176377 ER PT J AU Jacobsen, LK Giedd, JN Tanrikut, C Brady, DR Donohue, BC Hamburger, SD Kumra, S AlaghbandRad, J Rumsey, JM Rapoport, JL AF Jacobsen, LK Giedd, JN Tanrikut, C Brady, DR Donohue, BC Hamburger, SD Kumra, S AlaghbandRad, J Rumsey, JM Rapoport, JL TI Three-dimensional cortical morphometry of the planum temporale in childhood-onset schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ASYMMETRY; GYRUS; MRI AB Objective: Anomalous planum temporale asymmetry has been linked to both schizophrenia and dyslexia. The authors examined the planum temporale of adolescents with childhood-onset schizophrenia who had a high rate of prepsychotic language disorders. Method: Planum temporale area and asymmetry were measured in 16 right-handed adolescent patients with schizophrenia who had experienced onset of psychosis by age 12. The same measures were made in 16 healthy adolescents matched for age, sex, and handedness. Results: No differences between the healthy adolescents and those with schizophrenia in planum temporale area or asymmetry were observed. Prepsychotic language disorder predicted abnormal planum temporale asymmetry in the adolescents with schizophrenia. Conclusions: These findings do not support anomalous planum temporale asymmetry as a basis for psychopathology in childhood-onset schizophrenia. C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892. RP Jacobsen, LK (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,RM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 14 TC 24 Z9 24 U1 0 U2 1 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 MAY PY 1997 VL 154 IS 5 BP 685 EP 687 PG 3 WC Psychiatry SC Psychiatry GA WX130 UT WOS:A1997WX13000019 PM 9137128 ER PT J AU Guralnik, JM Leveille, SG AF Guralnik, JM Leveille, SG TI Race, ethnicity, and health outcomes - Unraveling the mediating role of socioeconomic status SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material RP Guralnik, JM (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892, USA. NR 11 TC 27 Z9 29 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSOC 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 MAY PY 1997 VL 87 IS 5 BP 728 EP 730 DI 10.2105/AJPH.87.5.728 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XC328 UT WOS:A1997XC32800003 PM 9184495 ER PT J AU Bulterys, M Morgenstern, H Weed, DL AF Bulterys, M Morgenstern, H Weed, DL TI Quantifying the expected vs potential impact of a risk-factor intervention program SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter ID NEURAL-TUBE DEFECTS; MORTALITY; PREVENTION; AMERICANS; SMOKING; HEALTH C1 UNIV NEW MEXICO,HLTH SCI CTR,CTR POPULAT HLTH,ALBUQUERQUE,NM 87131. UNIV CALIF LOS ANGELES,SCH MED,DEPT EPIDEMIOL,LOS ANGELES,CA. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. NR 11 TC 4 Z9 4 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC 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 MAY PY 1997 VL 87 IS 5 BP 867 EP 868 DI 10.2105/AJPH.87.5.867 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XC328 UT WOS:A1997XC32800036 PM 9184527 ER PT J AU Mann, M Shelhamer, JH Masur, H Gill, VJ Travis, W Solomon, D Manischewitz, J Stock, F Lane, HC Ognibene, FP AF Mann, M Shelhamer, JH Masur, H Gill, VJ Travis, W Solomon, D Manischewitz, J Stock, F Lane, HC Ognibene, FP TI Lack of clinical utility of bronchoalveolar lavage cultures for cytomegalovirus in HIV infection SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; PNEUMOCYSTIS-CARINII PNEUMONIA; NONSPECIFIC INTERSTITIAL PNEUMONITIS; VIRUS HIV; AIDS; DIAGNOSIS; MORTALITY; DISEASE; BLOOD; FLUID AB This study assessed the presence of cytomegalovirus (CMV) in bronchoalveolar ravage (BAL) in three subpopulations of HIV-infected patients and correlated its presence with clinical status during 3 mo of follow-up. Nineteen asymptomatic volunteers, six patients with CMV retinitis, and 46 patients with acute pulmonary symptoms underwent BAL and were assessed for CMV by cytopathology, conventional shell vial cultures, and antigen detection. Transbronchial biopsies were also obtained when possible and evaluated for histopathologic changes of CMV. All patients were followed for approximately 3 mo. Cytomegalovirus was detected in BAL in nine of 19 (47%) asymptomatic volunteers, in all six patients with CMV retinitis, and in 33 of 46 (72%) patients with pulmonary symptoms. Only one symptomatic patient with a positive CMV BAL culture developed clinically significant CMV pulmonary disease; this patient developed disseminated CMV and died. The only other death occurred in a patient with CMV retinitis who developed staphylococcal bacteremia. None of the asymptomatic volunteers or patients with CMV retinitis developed evidence of CMV pneumonia or any other organ disease with CMV. Cytomegalovirus is frequently detected in BAL from HIV-infected patients regardless of their pulmonary symptoms and its presence does not clinically predict significant pulmonary morbidity or mortality in 3 mo of follow-up. C1 NIH,DEPT CRIT CARE MED,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892. NIH,DEPT CLIN PATHOL,WARREN G MAGNUSON CLIN CTR,SERV CLIN PATHOL,BETHESDA,MD 20892. NCI,PATHOL LAB,SURG PATHOL SECT,BETHESDA,MD 20892. NCI,PATHOL LAB,CYTOPATHOL SECT,BETHESDA,MD 20892. CTR BIOL EVALUAT & RES,DIV VIRAL PROD,BETHESDA,MD. NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. US FDA,DIV ANTIVIRAL DRUG PROD,ROCKVILLE,MD 20857. NR 28 TC 26 Z9 26 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 MAY PY 1997 VL 155 IS 5 BP 1723 EP 1728 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA WY793 UT WOS:A1997WY79300037 PM 9154883 ER PT J AU Summers, RM AF Summers, RM TI Navigational aids for real-time virtual bronchoscopy SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Radiological-Society-of-North-America CY NOV, 1996 CL CHICAGO, IL SP Radiol Soc N Amer RP Summers, RM (reprint author), NIH, WARREN GRANT MAGNUSON CLIN CTR, DEPT DIAGNOST RADIOL,BLDG 10,RM 1C660, 10 CTR DR MSC 1182, BETHESDA, MD 20892 USA. NR 5 TC 77 Z9 78 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 1997 VL 168 IS 5 BP 1165 EP 1170 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WV568 UT WOS:A1997WV56800006 PM 9129406 ER PT J AU Doppman, JL AF Doppman, JL TI Question SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter ID INSULINOMAS RP Doppman, JL (reprint author), NIH,BETHESDA,MD 20892, USA. NR 4 TC 5 Z9 5 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 1997 VL 168 IS 5 BP 1376 EP 1377 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WV568 UT WOS:A1997WV56800052 PM 9129448 ER PT J AU Vargas, MP Vargas, HI Kleiner, DE Merino, MJ AF Vargas, MP Vargas, HI Kleiner, DE Merino, MJ TI Adrenocortical neoplasms: Role of prognostic markers MIB-1, p53, and RB SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE adrenal; adrenocortical neoplasms; MiB-1; p53; retinoblastoma gene product ID TUMOR SUPPRESSOR GENE; MUTATIONS; CARCINOMA; CANCERS AB Differentiation between benign and malignant adrenocortical neoplasms is made using a combination of clinical and pathologic parameters. Despite these parameters, it is still difficult to predict the biologic potential of some tumors. Forty adrenocortical lesions, including 10 hyperplasias, 10 adenomas, 12 carcinomas and eight metastatic/recurrent adrenocortical carcinomas were studied for the expression of MiB-1, p53, and the retinoblastoma gene product (RE) utilizing immunohistochemical techniques. The mean tumor proliferating fraction (TPF), expressed as the number of MiB-1-positive nuclei per 1,000 tumor cells, was 14.9 in adenomas, 31.5 in hyperplasias, 208.1 in carcinomas and 166.1 in recurrent or metastatic disease. None of the 20 benign lesions had a TPF of > 80, and only one of the 20 malignancies had a TPF of < 80. Nine of the 20 carcinomas were positive for p53. None of the benign lesions were p53 positive. Thirty-nine cases, including benign and malignant ones, were RE positive, and one was uninterpretable. We conclude that prognostic markers can be of great assistance in recognizing adrenocortical carcinomas. High TPF (> 80), as measured by staining with MiB-1, and positive p53 strongly correlate with malignant behavior and therefore may be useful in distinguishing benign from malignant adrenal lesions. Staining for RE does not appear to be a helpful technique. C1 NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NCI,SURG BRANCH,NIH,BETHESDA,MD 20892. OI Kleiner, David/0000-0003-3442-4453 NR 22 TC 55 Z9 55 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAY PY 1997 VL 21 IS 5 BP 556 EP 562 DI 10.1097/00000478-199705000-00008 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA WZ255 UT WOS:A1997WZ25500008 PM 9158680 ER PT J AU McCrae, RR Costa, PT AF McCrae, RR Costa, PT TI Personality trait structure as a human universal SO AMERICAN PSYCHOLOGIST LA English DT Article ID 5-FACTOR MODEL; BIG 5; CULTURE; PSYCHOLOGY; PERCEPTION; INVENTORY; LANGUAGE; SELF AB Patterns of covariation among personality traits in English-speaking populations can be summarized by the five-factor model (FFM). To assess the cross-cultural generalizability of the FFM, data from studies using 6 translations of the Revised NEO Personality Inventory (P. T. Costa & R. R. McCrae, 1992) were compared with the American factor structure. German, Portuguese; Hebrew, Chinese, Korean, and Japanese samples (N = 7,134) showed similar structures after varimax rotation of 5 factors. When targeted rotations were used, the American factor structure was closely reproduced, even at the level of secondary loadings. Because the samples studied represented highly diverse cultures with languages from 5 distinct language families, these data strongly suggest that personality trait structure is universal. RP McCrae, RR (reprint author), NIA, GERONTOL RES CTR, PERSONAL STRESS & COPING SECT, 4940 EASTERN AVE, BALTIMORE, MD 21224 USA. OI Costa, Paul/0000-0003-4375-1712 NR 51 TC 1141 Z9 1174 U1 64 U2 360 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD MAY PY 1997 VL 52 IS 5 BP 509 EP 516 DI 10.1037/0003-066X.52.5.509 PG 8 WC Psychology, Multidisciplinary SC Psychology GA WW854 UT WOS:A1997WW85400001 PM 9145021 ER PT J AU Hoagwood, K AF Hoagwood, K TI Interpreting nullity - The Fort Bragg experiment - A comparative success or failure? SO AMERICAN PSYCHOLOGIST LA English DT Article ID ADOLESCENT PSYCHOTHERAPY; CHILDREN RP Hoagwood, K (reprint author), NIMH,DIV EPIDEMIOL & SERV RES,CHILD & ADOLESCENT SERV RES BRANCH,5600 FISHERS LANE,ROOM 10C-06,ROCKVILLE,MD 20857, USA. NR 29 TC 26 Z9 26 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD MAY PY 1997 VL 52 IS 5 BP 546 EP 550 PG 5 WC Psychology, Multidisciplinary SC Psychology GA WW854 UT WOS:A1997WW85400005 PM 9145023 ER PT J AU Keohavong, P Zhu, D Whiteside, TL Swalsky, P Bakker, A Elder, EM Siegfried, JM Srivastava, S Finkelstein, SD AF Keohavong, P Zhu, D Whiteside, TL Swalsky, P Bakker, A Elder, EM Siegfried, JM Srivastava, S Finkelstein, SD TI Detection of infrequent and multiple K-ras mutations in human tumors and tumor-adjacent tissues SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID POLYMERASE CHAIN-REACTION; GENE-MUTATIONS; LUNG-CANCER; ONCOGENE MUTATIONS; ADENOCARCINOMA; AMPLIFICATION; ASSOCIATION; ACTIVATION; DIAGNOSIS; EVENT AB A sensitive method was developed and applied to examine the distribution of K-ras gene mutations in histologically differing areas of lung tissues obtained from lung cancer patients. This method, which combines polymerase chain reaction (PCR), mutation allele enrichment (MAE), and denaturing gradient gel electrophoresis (DGGE), allows detection of one K-ras mutant allele present in 10(4) to 10(5) wild-type alleles. It was applied to analyze mutations in codon 12 of the K-ras gene in 43 tissue sites microdissected from paraffin-embedded sections obtained from 8 archival cases of lung cancer, all previously shown to have codon 12 K-ras mutations by direct sequencing. In four cases, mutations were detected only in the tumor, while in the other four cases, the same mutations were also found in tissues adjacent to tumors, using the MAE + DGGE method. No mutations were detected among normal-appearing cells in areas distant from the tumors in any of the cases studied. These findings demonstrate that K-ras mutations can be detected at low frequencies in normal-appearing cells from tissues adjacent to the tumor in some lung cancer cases. In addition, this approach also allowed detection of multiple mutations in colorectal tissues obtained from colorectal cancer patients. Thus, the MAE + DGGE method may be applicable to study of K-ras mutations in premalignant or morphologically suspicious lesions in bronchial mucosa or other types of human cancer. (C) 1997 Academic Press. C1 UNIV PITTSBURGH,DEPT ENVIRONM & OCCUPAT HLTH,PITTSBURGH,PA 15213. UNIV PITTSBURGH,DEPT PATHOL,PITTSBURGH,PA 15213. UNIV PITTSBURGH,DEPT PHARMACOL,PITTSBURGH,PA 15213. UNIV PITTSBURGH,INST CANC,PITTSBURGH,PA 15213. NIH,BETHESDA,MD 20892. OI Keohavong, Phouthone/0000-0001-7812-4925 FU NCI NIH HHS [1-RO3-CA71609-01, CN-15393-02, P20-CA58235] NR 33 TC 27 Z9 27 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD MAY 1 PY 1997 VL 247 IS 2 BP 394 EP 403 DI 10.1006/abio.1997.2100 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WZ661 UT WOS:A1997WZ66100029 PM 9177704 ER PT J AU Trawoger, T Kolobow, T Cereda, M Sparacino, ME AF Trawoger, T Kolobow, T Cereda, M Sparacino, ME TI Tracheal mucus velocity remains normal in healthy sheep intubated with a new endotracheal tube with a novel laryngeal seal SO ANESTHESIOLOGY LA English DT Article DE equipment, cuffs; endotracheal tubes; gills; mechanism, mucociliary clearance; tracheal mucus velocity ID MUCOUS VELOCITY; MUCOCILIARY TRANSPORT; PRESSURE AB Background: Tracheal mucus velocity (TMV), an index of mucociliary clearance, is reduced markedly in patients intubated with standard endotracheal tubes (ETTs) with high-compliance low-pressure (hi-lo) cuffs. The authors developed a new ultra-thin walled ETT in which the inflatable cuff is replaced with a no-pressure seal, positioned at the level of the larynx. The seal consists of 12 to 20 toroidal layers of thin polyurethane film (''gills'') at the level of the vocal cords and prevents both air leak and fluid aspiration, The authors hypothesized that ETTs with the new laryngeal seal may impair TMV less than ETTs with inflated hi-lo cuffs do. Methods: The TMV was measured in seven healthy female sheep by radiographically tracking the motion of small discs of tantalum inserted into the trachea through a bronchoscope, The TMV was measured in spontaneously breathing sheep before intubation (baseline) and after intubation with either a hi-lo ETT (control group) or after intubation with a new ETT with gills (study group). Four to six weeks later, the studies were repeated, but the sheep that were previously in the control group served as the study group, and those in the study group served as controls. Results: Baseline TMV did not differ in the two groups, In the control group, TMV decreased significantly (by 67%) from baseline. In the study group, TMV did not differ significantly from baseline and remained steady during 3 h of intubation. Conclusions: The TMV does not change in sheep intubated with new ETTs with gills, The new ETTs may help promote a normal mucociliary clearance in patients who require ventilation. RP Trawoger, T (reprint author), NHLBI, SECT PULM & CARDIAC ASSIST DEVICES, PULM CRIT CARE MED BRANCH,NIH, 10 CTR DR, MSC-1590, BETHESDA, MD 20892 USA. NR 22 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 1997 VL 86 IS 5 BP 1140 EP 1144 PG 5 WC Anesthesiology SC Anesthesiology GA WX859 UT WOS:A1997WX85900019 ER PT J AU Bell, RA MayerDavis, EJ Jackson, Y Dresser, C AF Bell, RA MayerDavis, EJ Jackson, Y Dresser, C TI An epidemiologic review of dietary intake studies among American Indians and Alaska Natives: Implications for heart disease and cancer risk SO ANNALS OF EPIDEMIOLOGY LA English DT Review DE diet; American Indians Alaska Natives; ethnicity; nutrition epidemiology; heart disease; cancer ID CARDIOVASCULAR-DISEASE; PIMA-INDIANS; NUTRIENT INTAKE; ANTIOXIDANT VITAMINS; DIABETES-MELLITUS; BLOOD-PRESSURE; NORTH-CAROLINA; WOMEN; MORTALITY; OBESITY AB PURPOSE: Dietary factors play an important role in the occurrence of heart disease and cancer. While American Indians and Alaska Natives (AIANs) have unique heart disease and cancer mortality profiles, little is known about the effect of diet on heart disease and cancer risk in these populations. This paper reviews existing nutritional intake data from adult AIANs, and considers the potential impact of diet on heart disease and cancer in these communities. METHODS: A review of the literature was conducted using the Medline database system and other reference materials. Studies documenting nutrient intakes only were included in this review. Studies were limited to those among healthy, non-pregnant adults. RESULTS: A total of twelve reports from 1959 to 1996 were found. Sample sizes for the studies ranged from 20 to 575 subjects. Most studies were done among women, and a variety of nutritional assessment techniques (24 hour recall, food frequency questionnaire, multiple-day food record) were used. Most studies also had limited nutrient intake data, especially for dietary fiber and vitamin E. The majority of studies reported moderately high intakes of fat and saturated fat, and low intakes of polyunsaturated fat: and fiber. CONCLUSIONS: Based on the limited data, diet may play an important role in the heterogeneity of heart disease and cancer mortality in AIAN communities. More research is needed to assess the impact of diet on heart disease and cancer risk, including more longitudinal data, and data to assess the Validity and reliability of traditional methods of dietary assessment. (C) 1997 by Elsevier Science Inc. C1 ADM AGING,WASHINGTON,DC. NCI,PREVENT & CONTROL EXTRAMURAL BRANCH,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. RP Bell, RA (reprint author), WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,MED CTR BLVD,WINSTON SALEM,NC 27157, USA. NR 84 TC 12 Z9 12 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD MAY PY 1997 VL 7 IS 4 BP 229 EP 240 DI 10.1016/S1047-2797(97)00018-5 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XC102 UT WOS:A1997XC10200002 PM 9177104 ER PT J AU Chyou, PH Burchfiel, CM Yano, K Sharp, DS Rodriguez, BL Curb, JD Nomura, AMY AF Chyou, PH Burchfiel, CM Yano, K Sharp, DS Rodriguez, BL Curb, JD Nomura, AMY TI Obesity, alcohol consumption, smoking, and mortality SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE body mass index; alcohol; cigarette smoking; mortality ID JAPANESE-AMERICAN MEN; MALE BRITISH DOCTORS; BODY-MASS INDEX; ESOPHAGEAL CANCER; BLACK-MEN; WEIGHT; WOMEN AB PURPOSE: The goals of this study were to assess prospectively the impact of obesity, alcohol use, and smoking on total mortality and to test the etiologic hypothesis that subjects with two or more of these risk factors may experience an elevated risk of overall mortality. METHODS: Information on body mass index (BMI), alcohol intake, cigarette smoking, and other life-style factors was obtained from a cohort of 8006 Japanese-American men living in Hawaii. They were between 45 and 68 years of age at the initial examination (1965-1968). Alter 22 years of follow-up that included nearly 159,000 person-years of observation, 2667 deaths from all causes were identified. RESULTS: There was a significant quadratic (J-shaped) relation between BMI and overall mortality. A weaker J-shaped pattern in risk was also present for the intake of alcohol. A strong positive association was observed with pack-years of cigarette smoking. A synergistic interaction between BMI and alcohol was statistically significant (P = 0.0017). Specifically, men who had the lowest body mass (BMI < 21.21 kg/m(2)) and drank moderately to heavily (greater than or equal to 25 oz/mo) experienced a 63% excess risk (relative risk, 1.63; 95% confidence interval; 1.33 - 1.99) compared to a reference group composed of men who had intermediate body mass (BMI, 21.21 - 26.30 kg/m(2)) and drank occasionally to lightly (0.01 - 24.99 oz/mo). The increase in risk due to the interactive effect of Low BMI and high alcohol intake was stronger (and statistically significant) than when each of these risk factors was considered separately (excess risk, 28% and 2%, respectively). There was no significant interaction for BMI and cigarette smoking, for alcohol and cigarette smoking, or for the three factors combined. CONCLUSIONS: The most important finding of this study was that, in addition to confirming that cigarette smoking could shorten life, extreme (high or low) BMI values and high alcohol consumption are each potentially harmful to health, but even more so if moderate or heavy drinking is concomitant with low body mass, a possible indicator for low intake of nutrients. (C) 1991 by Elsevier Science Inc. C1 KUAKINI MED CTR,HONOLULU HEART PROGRAM,HONOLULU,HI 96817. MARSHFIELD CLIN FDN MED RES & EDUC,MARSHFIELD,WI 54449. UNIV HAWAII MANOA,DIV CLIN EPIDEMIOL,JOHN A BURNS SCH MED,HONOLULU,HI 96822. NHLBI,HONOLULU EPIDEMIOL RES UNIT,EPIDEMIOL & BIOMETRY PROGRAM,DIV EPIDEMIOL & CLIN APPLICAT,NIH,HONOLULU,HI. KUAKINI MED CTR,JAPAN HAWAII CANC STUDY,HONOLULU,HI 96817. FU NCI NIH HHS [R01 CA 33644]; NHLBI NIH HHS [N01-HC-05102] NR 32 TC 24 Z9 24 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD MAY PY 1997 VL 7 IS 4 BP 311 EP 317 DI 10.1016/S1047-2797(97)00019-7 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XC102 UT WOS:A1997XC10200013 PM 9177115 ER PT J AU McIntosh, I Clough, MV Schaffer, AA Francomano, CA McCormick, MK AF McIntosh, I Clough, MV Schaffer, AA Francomano, CA McCormick, MK TI Fine mapping of the nail-patella syndrome locus and integration of new markers into the 9q34 map. SO ANNALS OF HUMAN GENETICS LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,CTR MED GENET,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21287. NIH,LAB GENET DIS RES,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,CHARLESTOWN,MA 02129. NIH,NATL CTR HUMAN GENOME RES,MED GENET BRANCH,BETHESDA,MD 20892. RI Schaffer, Alejandro/F-2902-2012 NR 3 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD MAY PY 1997 VL 61 BP 216 EP 217 PN 3 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA XM185 UT WOS:A1997XM18500019 ER PT J AU Schuman, P Capps, L Peng, G Vazquez, J ElSadr, W Goldman, AI Alston, B Besch, CL Vaughn, A Thompson, MA Cobb, MN Kerkering, T Sobel, JD AF Schuman, P Capps, L Peng, G Vazquez, J ElSadr, W Goldman, AI Alston, B Besch, CL Vaughn, A Thompson, MA Cobb, MN Kerkering, T Sobel, JD TI Weekly fluconazole for the prevention of mucosal candidiasis in women with HIV infection - A randomized, double-blind, placebo-controlled trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE fluconazole; human immunodeficiency virus infections; candidiasis, vulvovaginal; candidiasis, oral; Candida albicans ID IMMUNODEFICIENCY-VIRUS-INFECTION; ESOPHAGEAL CANDIDIASIS; VAGINAL CANDIDIASIS; ORAL CANDIDIASIS; SAN-FRANCISCO; RESISTANT; AIDS; OROPHARYNGEAL; CANDIDOSIS; EMERGENCE AB Background: Candidiasis is a frequent complication of infection with the human immunodeficiency virus (HIV); however, few data exist about the natural history, prevention, and treatment of mucosal candidiasis in women. Objective: To evaluate the safety and effectiveness of weekly fluconazole prophylaxis for mucosal candidiasis in women infected with HIV. Design: Randomized, double-blind, placebo-controlled trial. Setting: 14 sites participating in the Community Programs for Clinical Research on AIDS (CPCRA). Patients: 323 women with HIV infection and CD4(+) cell counts of 300 cells/mm(3) br less. Intervention: 200 mg of fluconazole per week or placebo. Open-label fluconazole for candidiasis prophylaxis was permitted after two oropharyngeal or vaginal episodes or one esophageal episode. Measurements: Development of mucosal candidiasis, clinical and in vitro resistance of Candida species to fluconazole, survival, and adverse events. Results: After a median follow-up of 29 months, 72 of 162 patients receiving fluconazole and 93 of 161 patients receiving placebo had at least one episode of candidiasis (relative risk [RR], 0.56 [95% CI, 0.41 to 0.77]; P < 0.001). Weekly fluconazole was effective in preventing oropharyngeal candidiasis (RR, 0.50 [CI, 0.33 to 0.74]; P < 0.001) and vaginal candidiasis (RR, 0.64 [CI, 0.40 to 1.00]; P = 0.05) but not esophageal candidiasis (RR, 0.91 [CI, 0.48 to 1.72]; P > 0.2). Relative risks were similar for women who had a history of mucosal candidiasis (RR, 0.51 [CI, 0.35 to 0.75]) and those who did not (RR, 0.69 [CI, 0.35 to 1.34]). Absolute risk reduction for patients with a history of infection was 25.6 per 100 person-years, which is more than twice the reduction of 11.2 per 100 person-years seen in patients with no history of infection. This difference reflects the higher risk of patients who previously had an infection. Candida albicans was not usually resistant to fluconazole in vaginal specimens in clinical or in vitro settings; such resistance occurred in less than 5% of patients in each group. Conclusions: Weekly fluconazole (200 mg) seems to be safe and effective in preventing oropharyngeal and vaginal candidiasis. This regimen has a useful role in the management of HIV-infected women who are at risk for recurrent mucosal candidiasis. C1 DETROIT MED CTR,DETROIT,MI 48201. HARLEM HOSP MED CTR,NEW YORK,NY. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. NIH,BETHESDA,MD 20892. TULANE UNIV MED CTR HOSP & CLIN,NEW ORLEANS,LA. NEWARK COMMUNITY HLTH CTR,NEWARK,NJ. AIDS RES CONSORTIUM ATLANTA,ATLANTA,GA. ADDICT RES & TREATMENT CORP,BROOKLYN,NY. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,RICHMOND,VA 23298. RP Schuman, P (reprint author), WAYNE STATE UNIV,DIV INFECT DIS,HARPER PROFESS BLDG,4160 JOHN R RD,SUITE 2140,DETROIT,MI 48201, USA. NR 31 TC 79 Z9 81 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 MAY 1 PY 1997 VL 126 IS 9 BP 689 EP & PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA WW147 UT WOS:A1997WW14700003 PM 9139554 ER PT J AU Dalakas, MC AF Dalakas, MC TI Intravenous immune globulin therapy for neurologic diseases SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID GUILLAIN-BARRE-SYNDROME; MULTIFOCAL MOTOR NEUROPATHY; IMMUNOGLOBULIN THERAPY; GAMMA-GLOBULIN; MYASTHENIA-GRAVIS; PLASMA-EXCHANGE; KAWASAKI SYNDROME; DRUG-THERAPY; DOUBLE-BLIND; B-CELL AB High-dose intravenous immune globulin (IVIg) has emerged as an important therapy for various neurologic diseases. Different interpretations of clinical trial results; the expected benefit of IVIg compared with that of alternate therapies; and issues about IVIg's safety, cost, and mechanisms of action have raised concern and uncertainty among practitioners. To clarify these areas, this paper examines the clinical, serologic, and immunologic data on more than 110 patients with various autoimmune neurologic diseases who received IVIg during the past 6 years at the National Institute of Neurological Disorders and Stroke. It also reviews work by other investigators on the efficacy, risks, benefits, and mechanisms of the action of IVIg in these diseases. In controlled clinical trials, IVIg has been effective in treating the Guillain-Barre syndrome, multifocal motor neuropathy, chronic inflammatory demyelinating polyneuropathy, and dermatomyositis. In other controlled or open-label trials and case reports, IVIg produced improvement in several patients with the Lambert-Eaton myasthenic syndrome and myasthenia gravis but had a variable, mild, or unsubstantiated benefit in some patients with inclusion-body myositis, paraproteinemic IgM demyelinating polyneuropathy, certain intractable childhood epilepsies, polymyositis, multiple sclerosis, optic neuritis, and the stiff-man syndrome. The primary adverse reaction was headache; aseptic meningitis, skin reactions, thromboembolic events, and renal tubular necrosis occurred rarely. The most relevant immunomodulatory actions of IVIg, operating alone or in combination, are inhibition of complement deposition, neutralization of cytokines, modulation of Fc-receptor-mediated phagocytosis, and downregulation of autoantibody production. Therapy with IVIg is effective for certain autoimmune neurologic diseases, but its spectrum of efficacy has not been fully established. Additional controlled clinical trials are needed. RP Dalakas, MC (reprint author), NIH,NINDS,BLDG 10,ROOM 4N248,10 CTR DR,MSC 1382,BETHESDA,MD 20892, USA. NR 97 TC 176 Z9 181 U1 0 U2 5 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 1 PY 1997 VL 126 IS 9 BP 721 EP 730 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA WW147 UT WOS:A1997WW14700008 PM 9139559 ER PT J AU Gibril, F Jensen, RT AF Gibril, F Jensen, RT TI Somatostatin receptor scintigraphy in the Zollinger-Ellison syndrome - Response SO ANNALS OF INTERNAL MEDICINE LA English DT Letter RP Gibril, F (reprint author), NIDDKD,BETHESDA,MD 20892, USA. NR 5 TC 2 Z9 2 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 MAY 1 PY 1997 VL 126 IS 9 BP 741 EP 742 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA WW147 UT WOS:A1997WW14700020 ER PT J AU Schiffmann, R Tedeschi, G Kinkel, RP Trapp, BD Frank, JA Kaneski, CR Brady, RO Barton, NW Nelson, L Yanovski, JA AF Schiffmann, R Tedeschi, G Kinkel, RP Trapp, BD Frank, JA Kaneski, CR Brady, RO Barton, NW Nelson, L Yanovski, JA TI Leukodystrophy in patients with ovarian dysgenesis SO ANNALS OF NEUROLOGY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the Child-Neurology-Society CY OCT 24-28, 1995 CL BALTIMORE, MD SP Child Neurol Soc ID NERVOUS-SYSTEM HYPOMYELINATION; CHILDHOOD ATAXIA; BRAIN; COMPLICATIONS; GALACTOSEMIA; SPECTROSCOPY; RECEPTORS; FAILURE AB We describe clinical, biochemical, pathological, and spectroscopic findings in 4 women, aged 15 to 29 years, from three unrelated families who had a unique combination of a central nervous system white matter disease and primary ovarian failure. ALL had normal initial development but 3 had borderline low IQ and academic difficulties in primary school. Puberty did not develop in 2 patients and was arrested in a third patient. The fourth patient had premature ovarian failure at the age of 13 years. Head magnetic resonance imaging showed diffuse white matter disease, with frontal cortical atrophy in the most clinically advanced patient. All patients had normal karyotype and normal findings on extensive evaluations for known leukodystrophies, for other metabolic diseases, and for causes of ovarian failure. Proton magnetic resonance spectroscopic imaging showed reduction of choline-containing compounds in the affected white matter in all patients and reduction of N-acetylaspartate in the unaffected frontal white matter of 2 patients. All patients had evidence of primary gonadal insufficiency with a normal hypothalamic-hypophyseal axis. Pathological analysis showed streak ovaries in 1 patient and signs of hypomyelination, and gliosis on brain biopsy in another patient. In conclusion, we present a novel group of patients who have in common leukodystrophy, primary ovarian dysfunction, and magnetic resonance spectroscopic abnormalities. C1 NINCDS,NEUROIMAGING BRANCH,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,OFF DIRECTOR,WARREN G MAGNUSON CLIN CTR,NIH,BETHESDA,MD 20892. CLEVELAND CLIN FDN,DEPT NEUROL,CLEVELAND,OH 44195. CLEVELAND CLIN FDN,DEPT NEUROSCI,CLEVELAND,OH 44195. RP Schiffmann, R (reprint author), NINCDS,DEV & METAB NEUROL BRANCH,NIH,BLDG 10,ROOM 3D03,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Kaneski, Christine/0000-0003-1453-2502 NR 33 TC 40 Z9 40 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 1997 VL 41 IS 5 BP 654 EP 661 DI 10.1002/ana.410410515 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WZ809 UT WOS:A1997WZ80900014 PM 9153528 ER PT J AU Calabresi, PA Tranquill, LR Dambrosia, JM Stone, LA Maloni, H Bash, CN Frank, JA McFarland, HF AF Calabresi, PA Tranquill, LR Dambrosia, JM Stone, LA Maloni, H Bash, CN Frank, JA McFarland, HF TI Increases in soluble VCAM-1 correlate with a decrease in MRI lesions in multiple sclerosis treated with interferon beta-1b SO ANNALS OF NEUROLOGY LA English DT Article ID CIRCULATING ADHESION MOLECULES; TUMOR-NECROSIS-FACTOR; CEREBROSPINAL-FLUID; E-SELECTIN; SERUM; MYELOPATHY; RECEPTOR AB Interferon beta-1b reduces clinical exacerbations and disease activity in multiple sclerosis as shown by magnetic resonance imaging, but the mechanism of action is unknown. We investigated the correlation between the levels of soluble adhesion molecules and a reduction in contrast-enhancing lesions on gadopentetate dimeglumine magnetic resonance images after treatment with interferon beta-1b. We determined levels of soluble vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin, L-selectin, and tumor necrosis factor receptor (60 kd) in monthly serum samples from patients with definite multiple sclerosis before and during treatment with interferon beta-1b. The level of soluble adhesion molecules was correlated with the number of newly enhancing lesions on monthly contrast-enhanced images. Levels of soluble vascular cell adhesion molecule during treatment were significantly increased compared to control or pretreatment values. The median levels (ng/ml) of this adhesion molecule were 580.3 (range; 373.0-640.7) for the healthy subjects, and 551.4 (489.7-875.5) for patients prior to treatment and 847.9 (591.5-1,232.9) during treatment. Levels of the other soluble adhesion molecules and soluble tumor necrosis factor receptor were not significantly changed during treatment. The increase in soluble vascular cell adhesion molecule correlated with a decrease in the number of contrast-enhancing lesions on magnetic resonance images. These data suggest a novel mechanism of action for interferon beta-1b by direct interference with the adhesion cascade, which may prevent activated T cells from trafficking into the central nervous system. C1 NINCDS,BIOMETRY & FIELD STUDIES BRANCH,NIH,BETHESDA,MD 20892. NIH,LAB DIAGNOST RADIOL RES,OFF DIRECTOR,BETHESDA,MD 20892. MAYO CLIN SCOTTSDALE,DEPT NEUROL,SCOTTSDALE,AZ. RP Calabresi, PA (reprint author), NINCDS,NEUROIMMUNOL BRANCH,NIH,BLDG 10,ROOM 5B-16,10 CTR DR,MSC-1400,BETHESDA,MD 20892, USA. NR 28 TC 137 Z9 138 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 1997 VL 41 IS 5 BP 669 EP 674 DI 10.1002/ana.410410517 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WZ809 UT WOS:A1997WZ80900016 PM 9153530 ER PT J AU Jakowlew, SB Moody, TW Mariano, JM AF Jakowlew, SB Moody, TW Mariano, JM TI Transforming growth factor-beta receptors in human cancer cell lines: Analysis of transcript, protein and proliferation SO ANTICANCER RESEARCH LA English DT Article DE TGF-beta; receptor; cancer; breast; ovary; prostate ID HUMAN-PROSTATE-CANCER; II RECEPTOR; GENETIC INSTABILITY; CARCINOMA CELLS; TGF-BETA; EXPRESSION; PROGRESSION; INHIBITION; CLONING; LEADS AB Transforming growth factor beta (TGF-beta) is a growth regulator which affects multiple cellular functions through the TGF-beta type I and type II receptor (TGF-beta RT and TGF-beta RII) serine/threonine kinases. In this study, the expression of TGF-beta RI and RII was investigated by northern blot, reverse transcription-polymerase chain reaction (RT-PCR) and western blot analyses in human breast (MCF-7 and T-47D), ovary (CP70 and OVT2) and prostate (LNCaP, DU145 and PC3) cancer cell lines. Northern blot analysis showed expression of TCF-beta RI and TGF-beta RII mRNAs in all cell lines examined except for MCF-7 and LNCaP, respectively. In contrast, RT-PCR showed that all of the cell lines examined express TGF-beta RI and RII transcripts using specific primer oligonucleotides. Western blot analysis demonstrated that all of the cancer cell lines examined express TGF-beta RI and RII proteins. Southern blot analysis showed there were differences in the restriction enzyme digestion patterns for TGF-beta RI and RII of T47D compared to MCF-7, PC3 and LNCaP. Also, the addition of TGF-beta 1 to the breast and prostate cancer cells inhibited colony formation in soft agarose. Our studies show that in cancer cells, relatively low levels of TGF-beta receptor transcripts may result in protein production and inhibition of cell proliferation by TGF-beta. RP Jakowlew, SB (reprint author), NCI,MED BRANCH,9610 MED CTR DR,SUITE 300,ROCKVILLE,MD 20850, USA. NR 41 TC 35 Z9 35 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 MAY-JUN PY 1997 VL 17 IS 3C BP 1849 EP 1860 PG 12 WC Oncology SC Oncology GA XH618 UT WOS:A1997XH61800001 PM 9216635 ER PT J AU TerHaar, E Hamel, E Balachandran, R Day, BW AF TerHaar, E Hamel, E Balachandran, R Day, BW TI Cellular targets of the anti-breast cancer agent Z-1,1-dichloro-2,3-diphenylcyclopropane: Type II estrogen binding sites and tubulin SO ANTICANCER RESEARCH LA English DT Article DE analog II; Z-alpha-chlorochalcone; breast cancer; tubulin; type II estrogen binding sites ID ENDOGENOUS MAMMALIAN METABOLITE; MAMMARY-TUMOR GROWTH; HAMSTER V79 CELLS; COLCHICINE SITE; RAT UTERUS; ANALOG-II; POLYMERIZATION; ANTIESTROGENS; MICROTUBULES; INHIBITION AB Z-1,1-dichloro-2,3-diphenylcyclopropane (a.k.a. Analog II, Air) is a known anti-breast cancer agent with apparent antiestrogenic effects and remarkably low toxicity in rodents. We have recently shown that All and its major metabolite Z-alpha-chlorochalcone (ZCC) inhibit proliferation of both estrogen-responsive and -nonresponsive human breast cancer cells, suggesting its mechanism is not mediated by the type I estrogen receptor (ER). The present studies were performed to begin to define the molecular targets of A(II) and ZCC Based on the compounds' structures and actions, we hypothesized that their effects could be due to interaction at type II estrogen binding sites (EBSII) and/or cellular microtubules. The affinities of A(II), ZCC and the positive control diethylstilbestrol (DES) for the ER (in MCF-7 and MCF-7/LY2 cells) and EBSII (in MCF-7, MCF-7/LY2, and MDA-MB231 cells) were determined with a whole cell assay for displacement of [H-3]estradiol. The kinetics of their effects on cellular microtubules and cell cycle distribution of human breast cancel cells were measured by indirect immunofluorescence and flow cytometry. Their abilities to inhibit assembly of isolated tubulin in vitro were determined. A(II), ZCC, and DES had similar affinities for the EBSII in the three cell lines. Neither AII nor ZCC displaced [H-3]estradiol from the ER in MCF-7 cells, whereas DES did. The microtubule network of MDA-MB231 cells exposed to 100 mu M A(II) of 10 mu M ZCC began to disassemble within 1 hour of treatment and was completely diffuse after 6 hour of exposure to either drug. A(II) inhibited in vitro assembly of tubulin, with an IC50 of 6.7 +/- 0.9 mu M, while ZCC was inactive below 40 mu M. Both drugs caused accumulation of the cells in the G(2)/M phase of the cell cycle. The evidence suggests that the antitumor action of Am is mediated at least in part through the EBSII and/or perturbation of tubulin microtubule dynamics. A(II) thus represents a new lead compound for design and discovery of novel antitumor agents directed against the EBSII and/or microtubules. C1 UNIV PITTSBURGH,DEPT ENVIRONM & OCCUPAT HLTH,PITTSBURGH,PA 15238. UNIV PITTSBURGH,DEPT PHARMACEUT SCI,PITTSBURGH,PA 15238. UNIV PITTSBURGH,PITTSBURGH CANC INST,PITTSBURGH,PA 15238. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT DIAGNOSIS & CTR,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [CA 57288] NR 40 TC 9 Z9 9 U1 1 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 MAY-JUN PY 1997 VL 17 IS 3C BP 1861 EP 1869 PG 9 WC Oncology SC Oncology GA XH618 UT WOS:A1997XH61800002 PM 9216636 ER PT J AU Humphrey, RW Ohagen, A Davis, DA Fukazawa, T Hayashi, H Hoglund, S Mitsuya, H Yarchoan, R AF Humphrey, RW Ohagen, A Davis, DA Fukazawa, T Hayashi, H Hoglund, S Mitsuya, H Yarchoan, R TI Removal of human immunodeficiency virus type 1 (HIV-1) protease inhibitors from preparations of immature HIV-1 virions does not result in an increase in infectivity or the appearance of mature morphology SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID GAG POLYPROTEIN; PARTICLE FORMATION; IN-VITRO; MATURATION; ALLOPHENYLNORSTATINE; PROTEINASE; EXPRESSION; RITONAVIR; CLEAVAGE; INVITRO AB The processing of gag and gag-pol polyproteins by human immunodeficiency virus type 1 (HIV-1) protease is a crucial step in the formation of infectious HIV-1 virions. In this study, we examine whether particles produced in the presence of inhibitors of HIV-1 protease can subsequently undergo gag polyprotein cleavage with restoration of infectivity following removal of the inhibitors, Viral particles produced during 7 days of culture in the presence of the protease inhibitors KNI-272 (10 mu M) and saquinavir (5 mu M) contained predominantly p55(gag) polyprotein but little or no p24(gag) cleavage product, Following resuspension of the particles in medium free of the inhibitor, some gag polyprotein processing was detected in particles produced from the KNI-272-treated cells, but not from the saquinavir-treated cells within the first 3 h. However, the majority of the protein remained as p55(gag) throughout a 48-h experimental period, The infectivity (50% tissue culture infective dose per milliliter) of the viral particles from KNI-272-treated cells was 10(6)-fold lower than that of control particles and did not significantly increase over the 48 h after the inhibitor was removed, despite the apparent return of protease function in a subset of these virions, This failure to restore infectivity was due neither to a reduction in the number of particles produced by protease inhibitor-treated cells nor to a failure of HIV RNA to be packaged in the virions. These particles also failed to express the mature phenotype by electron microscopy, Thus, while some processing of the gag polyprotein can occur in isolated HN virions, this does not appear to be sufficient to restore infectivity in the majority of particles, This finding suggests that there may be constraints on postbudding polyprotein processing in the production of viable particles. These results should have positive implications regarding the use of protease inhibitors as anti-HN drugs. C1 NCI,HIV & AIDS MALIGNANCY BRANCH,NIH,BETHESDA,MD 20892. NCI,MED BRANCH,NIH,BETHESDA,MD 20892. UNIV UPPSALA,CTR BIOMED,DEPT BIOCHEM,S-75123 UPPSALA,SWEDEN. JAPAN ENERGY CORP,PHARMACEUT & BIOTECHNOL LAB,TODA,SAITAMA 335,JAPAN. NR 28 TC 13 Z9 13 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 MAY PY 1997 VL 41 IS 5 BP 1017 EP 1023 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA WX583 UT WOS:A1997WX58300025 PM 9145862 ER PT J AU Hiraiwa, M Martin, BM Kishimoto, Y Conner, GE Tsuji, S OBrien, JS AF Hiraiwa, M Martin, BM Kishimoto, Y Conner, GE Tsuji, S OBrien, JS TI Lysosomal proteolysis of prosaposin, the precursor of saposins (sphingolipid activator proteins): Its mechanism and inhibition by ganglioside SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID CATHEPSIN-D; TRANSPORT; MEMBRANES; BINDING AB Saposins A, B, C, and D, which are required for the enzymatic hydrolysis of sphingolipids by specific lysosomal hydrolases, are produced by proteolytic processing of their common precursor protein, prosaposin. Our previous observation suggested that lysosomal cathepsin D may be involved in the proteolysis of prosaposin. Herein we report the involvement of cathepsin D in the proteolytic processing of prosaposin. An antibody against human placental cathepsin D blocked the proteolytic activity toward prosaposin in a human testicular lysosomal protease mixture (glycoprotein fraction). On immunoblot analysis using a monoclonal antibody against human saposin C, cathepsin D showed a similar proteolytic pattern as that of a human testicular glycoprotein fraction and hydrolyzed prosaposin into products of 48 and 29 kDa. The K-m and V-max values were 0.9 mu M and 167 nmol/h/mg, respectively. N-Terminal sequence analysis indicated that the 48-kDa band was a mixture of two trisaposins, including domains for saposins A, B, and C and saposins B, C, and D, respectively. A similar study also showed that the 29-kDa band contained two disaposins, including domains for saposins A and B and saposins C and D, respectively. By longer treatment with cathepsin D, disaposins were further processed into mature saposin A and small fragments (14.5-17.5 kDa) containing individual saposins and portions of interdomain sequences. These small fragments were no longer processed by cathepsin D, but trimmed to fragments having similar molecular sizes (10.5-11.5 kDa) to those of mature saposins by a rat lysosome preparation. These findings indicated that cathepsin D is involved in the maturation of saposins but that, in addition to cathepsin D, other proteases appear to be involved in the maturation of saposin B, C, and D in lysosomes. Gangliosides, which specifically form complexes with prosaposin and saposins, inhibit proteolysis of prosaposin by cathepsin D. This finding indicates that prosaposin may be protected from lysosomal proteolysis by forming a complex with gangliosides in vivo. (C) 1997 Academic Press. C1 NIMH,CLIN NEUROSCI BRANCH,MOL NEUROGENET SECT,BETHESDA,MD 20892. UNIV MIAMI,SCH MED,DEPT CELL BIOL & ANAT,MIAMI,FL 33101. NIIGATA UNIV,BRAIN RES INST,DEPT NEUROL,NIIGATA 951,JAPAN. RP Hiraiwa, M (reprint author), UNIV CALIF SAN DIEGO,SCH MED,DEPT NEUROSCI,CTR MOL GENET,LA JOLLA,CA 92093, USA. NR 31 TC 71 Z9 72 U1 0 U2 5 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 MAY 1 PY 1997 VL 341 IS 1 BP 17 EP 24 DI 10.1006/abbi.1997.9958 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WX134 UT WOS:A1997WX13400003 PM 9143348 ER PT J AU Litman, RE Torrey, EF Hommer, DW Radant, AR Pickar, D Weinberger, DR AF Litman, RE Torrey, EF Hommer, DW Radant, AR Pickar, D Weinberger, DR TI A quantitative analysis of smooth pursuit eye tracking in monozygotic twins discordant for schizophrenia SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID MOVEMENT DYSFUNCTIONS; GENETIC TRANSMISSION; AFFECTIVE-DISORDERS; LINKAGE; MARKERS; ABNORMALITIES; CHROMOSOME-5; RELATIVES; FAMILIES; SACCADES AB Background: Previous studies of discordant monozygotic (MZ) twins have suggested that abnormal smooth pursuit eye tracking is an indicator of genetic liability for schizophrenia. We attempted to replicate this in a different sample of twins. Methods: Probands from 12 sets of MZ twins discordant for schizophrenia who met DSM-III-R criteria for schizophrenia or schizoaffective disorder and their co-twins without psychiatric diagnosis (except 2 with a history of substance abuse) and 12 sets of normal control MZ twins. Psychiatric diagnosis was based on Structured Clinical Interview; monozygosity was based on analysis of 19 red blood cell antigens. Smooth pursuit eye movement gain (equal to the ratio of eye-target velocity) and numbers, amplitudes, and subtypes of saccadic eye movements were compared. Measures were derived from computer analysis of digitized infrared oculographic recordings of constant velocity (16.67 degrees per second) smooth pursuit eye tracking. Results: Quantitative measures of eye tracking for the affected twin were inferior to those of the unaffected co-twin, with affected twins showing significant decreases in gain and significant increases in numbers and amplitudes of total and intrusive saccades. Moreover, whereas means for the group of affected twins differed significantly from those of normal controls on measures of gain and total saccades, means for the group of unaffected co-twins were well within the normal range. Conclusions: These data are consistent with the hypothesis that abnormal eye tracking is associated with the expression of illness, or phenotype, in schizophrenia, at least in this twin sample. The data raise questions regarding the use of eye tracking measurement for identifying putative gene carriers among at-risk relatives in genetic linkage studies of schizophrenia. C1 NIMH,EXPT THERAPEUT BRANCH,NIH,BETHESDA,MD 20892. NIMH,CLIN BRAIN DISORDERS BRANCH,NIH,BETHESDA,MD 20892. NIAAA,NIH,BETHESDA,MD 20892. VET AFFAIRS MED CTR,SEATTLE,WA 98108. NR 73 TC 24 Z9 24 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAY PY 1997 VL 54 IS 5 BP 417 EP 426 PG 10 WC Psychiatry SC Psychiatry GA WY633 UT WOS:A1997WY63300004 PM 9152095 ER PT J AU Schooler, NR Keith, SJ Severe, JB Matthews, SM Bellack, AS Glick, ID Hargreaves, WA Kane, JM Ninan, PT Frances, A Jacobs, M Lieberman, JA Mance, R Simpson, GM Woerner, MG AF Schooler, NR Keith, SJ Severe, JB Matthews, SM Bellack, AS Glick, ID Hargreaves, WA Kane, JM Ninan, PT Frances, A Jacobs, M Lieberman, JA Mance, R Simpson, GM Woerner, MG TI Relapse and rehospitalization during maintenance treatment of schizophrenia - The effects of dose reduction and family treatment SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID INTERMITTENT NEUROLEPTIC PROPHYLAXIS; CONTROLLED TRIAL; FOLLOW-UP; BEHAVIORAL INTERVENTION; COMMUNITY MANAGEMENT; SOCIAL-INTERVENTION; AFTERCARE TREATMENT; GERMAN MULTICENTER; EXPRESSED EMOTION; NEGATIVE SYMPTOMS AB Background: Previous studies have examined dose reduction and family treatment in schizophrenia, but none has examined their interaction. This study assessed the impact of dose reduction of antipsychotic medication and family treatment on relapse and rehospitalization during maintenance treatment. Methods: Subjects were 313 male and female outpatients at 5 centers with a DSM-III-R diagnosis of schizophrenia or schizoaffective disorder. In a 3x2 design, subjects were randomized to 1 of 3 medication strategies using fluphenazine decanoate under double-blind conditions: continuous moderate dose (standard) (12.5-50 mg every 2 weeks); continuous low dose (2.5-10 mg every 2 weeks); or targeted, early intervention (fluphenazine only when symptomatic). Subjects also were randomized to 1 of 2 family treatment strategies (supportive or applied). Supportive family management involved monthly group meetings. The more intensive applied family management involved monthly group meetings and home visits where communication and problem-solving skills were taught. Patients and families were treated and assessed for 2 years. Results: Both continuous low-dose and targeted treatment increased use of rescue medication and relapse; only targeted treatment increased rehospitalization. This pattern was consistent across both family treatments; there were no differences between family treatments. Conclusions: These findings reaffirm the value of antipsychotic medication in preventing relapse and rehospitalization. The absence of family treatment differences may be because both conditions engaged families. C1 NIMH,DIV CLIN & TREATMENT RES,ROCKVILLE,MD 20857. MED COLL PENN & HAHNEMANN UNIV,EASTERN PENN PSYCHIAT INST,DEPT PSYCHIAT,PHILADELPHIA,PA 19129. CORNELL UNIV,MED CTR,PAYNE WHITNEY CLIN,DEPT PSYCHIAT,NEW YORK,NY 10021. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO GEN HOSP,DEPT PSYCHIAT,SAN FRANCISCO,CA. HILLSIDE HOSP,LONG ISL JEWISH MED CTR,DEPT PSYCHIAT,NEW HYDE PK,NY. EMORY UNIV,DEPT PSYCHIAT,GRADY MEM HOSP,ATLANTA,GA 30322. RP Schooler, NR (reprint author), UNIV PITTSBURGH,WESTERN PSYCHIAT INST & CLIN,DEPT PSYCHIAT,SCH MED,3811 OHARA ST,PITTSBURGH,PA 15213, USA. FU NIMH NIH HHS [UO1 MH39992, UO1 MH39998, UO1 MH40007] NR 58 TC 240 Z9 248 U1 6 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAY PY 1997 VL 54 IS 5 BP 453 EP 463 PG 11 WC Psychiatry SC Psychiatry GA WY633 UT WOS:A1997WY63300008 PM 9152099 ER PT J AU Cohen, RM Nordahl, TE Semple, WE Andreason, P Litman, RE Pickar, D AF Cohen, RM Nordahl, TE Semple, WE Andreason, P Litman, RE Pickar, D TI The brain metabolic patterns of clozapine- and fluphenazine-treated patients with schizophrenia during a continuous performance task SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL GLUCOSE-METABOLISM; OBSESSIVE-COMPULSIVE SYMPTOMS; PREFRONTAL SUBSTRATE; SUSTAINED ATTENTION; MEDICATED PATIENTS; BASAL GANGLIA; NEUROLEPTICS; FLUORODEOXYGLUCOSE; CHLORPROMAZINE AB Background: The comparison of the effects of 2 classes of neuroleptic drugs on regional brain functional activities may reveal common mechanisms of antipsychotic drug efficacy. Methods: The regional cerebral glucose metabolic rates of patients with schizophrenia who were and were not receiving neuroleptic drugs and normal control subjects were obtained by positron emission tomography using fludeoxyglucose F 18 as the tracer. Results: Compared with normal controls and patients not receiving medication, fluphenazine hydrochloride- and clozapine-treated patients had lower global gray matter absolute metabolic rates throughout the cortex. When normalized regional glucose metabolic rates were examined, both medications lowered rates in the superior prefrontal cortex and increased rates in the limbic cortex. Fluphenazine, but not clozapine, increased metabolic rates in the subcortical and lateral temporal lobes, whereas clozapine, but not fluphenazine, decreased inferior prefrontal cortex activity. Conclusions: These changes are consistent with the idea that neuroleptic drugs lead to ''compensation'' and ''adaptation'' rather than ''normalization'' of the functional activities of brain structures in schizophrenia. The overall similarity of their global and regional metabolic effects suggests that both classes of antipsychotic drugs share some common mechanisms of action. One possibility is that of inducing a shift in the balance of cortical to limbic cortex activity. Differential effects in the inferior prefrontal cortex and the basal ganglia might underlie differences in the therapeutic efficacy and side effect profile of clozapine and fluphenazine. C1 NIMH, EXPT THERAPEUT BRANCH, BETHESDA, MD 20892 USA. RP Cohen, RM (reprint author), NIMH, CLIN BRAIN IMAGING SECT,CEREBRAL METAB LAB,BLDG 36, ROOM 1A05,36 CONVENT DR, MSC 4030, BETHESDA, MD 20892 USA. RI Nordahl, Thomas/J-7643-2013 OI Nordahl, Thomas/0000-0002-8627-0356 NR 45 TC 53 Z9 53 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAY PY 1997 VL 54 IS 5 BP 481 EP 486 PG 6 WC Psychiatry SC Psychiatry GA WY633 UT WOS:A1997WY63300011 PM 9152102 ER PT J AU Rumsey, JM Nace, K Donohue, B Wise, D Maisog, JM Andreason, P AF Rumsey, JM Nace, K Donohue, B Wise, D Maisog, JM Andreason, P TI A positron emission tomographic study of impaired word recognition and phonological processing in dyslexic men SO ARCHIVES OF NEUROLOGY LA English DT Article ID DEVELOPMENTAL DYSLEXIA; PET IMAGES; ACTIVATION; SKILLS; CORTEX; MEMORY AB Background: Developmental dyslexia is characterized by impaired word recognition, which is thought to result from deficits in phonological processing. Improvements during the course of development are thought to disproportionately involve orthographic components of reading; phonological deficits persist into adulthood. Objective: To localize the neural correlates of impaired word recognition and phonological processing in men with developmental dyslexia. Methods: Regional cerebral blood flow was measured with oxygen 15 positron emission tomography in 17 men with dyslexia and in 14 matched controls during the performance of phonological and orthographic tasks-pronunciation (reading aloud) and lexical decision making-designed to activate posterior and anterior perisylvian cortices, respectively. Results: Altered patterns of activation (reduced activation, unusual deactivation) were seen in dyslexic men in mid- to posterior temporal cortex bilaterally and in inferior parietal cortex, predominantly on the left, during both pronunciation and decision making. In contrast, dyslexic men demonstrated essentially normal activation of left inferior frontal cortex during both phonological and orthographic decision making. Conclusion: These, along with prior findings, are compatible with a hypothesis of bilateral involvement of posterior temporal and parietal cortices in dyslexia. C1 NIMH, PSYCHOL & PSYCHOPATHOL LAB, BETHESDA, MD 20892 USA. US FDA, DIV NEUROPHARMACOL DRUG PROD, ROCKVILLE, MD 20857 USA. RP Rumsey, JM (reprint author), NIMH, CHILD PSYCHIAT BRANCH, BLDG 10, ROOM 6N240, BETHESDA, MD 20892 USA. NR 41 TC 212 Z9 215 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAY PY 1997 VL 54 IS 5 BP 562 EP 573 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA WY809 UT WOS:A1997WY80900010 PM 9152113 ER PT J AU Lertsumitkul, S Whitcup, SM Chan, CC AF Lertsumitkul, S Whitcup, SM Chan, CC TI Ocular manifestations of disseminated intravascular coagulation in a patient with the acquired immunodeficiency syndrome SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article C1 NEI,BETHESDA,MD 20892. NR 3 TC 4 Z9 4 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAY PY 1997 VL 115 IS 5 BP 676 EP 677 PG 2 WC Ophthalmology SC Ophthalmology GA WY804 UT WOS:A1997WY80400024 PM 9152141 ER PT J AU Bagarazzi, ML McCarthy, J Kim, IK Reynolds, J Nutman, T Watson, B AF Bagarazzi, ML McCarthy, J Kim, IK Reynolds, J Nutman, T Watson, B TI Picture of the month - Filariasis SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article C1 UNIV PENN,CHILDRENS HOSP PHILADELPHIA,SCH MED,DIV ALLERGY IMMUNOL & INFECT DIS,PHILADELPHIA,PA 19104. MED COLL PENN & HAHNEMANN UNIV,DEPT NUCL MED,PHILADELPHIA,PA. NIH,PARASIT DIS LAB,BETHESDA,MD 20892. RI McCarthy, James/C-1681-2009 NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD MAY PY 1997 VL 151 IS 5 BP 521 EP 522 PG 2 WC Pediatrics SC Pediatrics GA WY810 UT WOS:A1997WY81000016 PM 9158448 ER PT J AU Langford, CA Sneller, MC AF Langford, CA Sneller, MC TI Finding a valid model for antineutrophil cytoplasmic antibody-related vasculitis: Reply SO ARTHRITIS AND RHEUMATISM LA English DT Letter RP Langford, CA (reprint author), NIAID,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 1997 VL 40 IS 5 BP 987 EP 987 DI 10.1002/art.1780400536 PG 1 WC Rheumatology SC Rheumatology GA WX862 UT WOS:A1997WX86200034 ER PT J AU Zheng, ZJ Sharrett, AR Chambless, LE Rosamond, WD Nieto, FJ Sheps, DS Dobs, A Evans, GW Heiss, G AF Zheng, ZJ Sharrett, AR Chambless, LE Rosamond, WD Nieto, FJ Sheps, DS Dobs, A Evans, GW Heiss, G TI Associations of ankle-brachial index with clinical coronary heart disease, stroke and preclinical carotid and popliteal atherosclerosis: The atherosclerosis risk in communities (ARIC) study SO ATHEROSCLEROSIS LA English DT Article DE peripheral arterial disease; coronary heart disease; stroke; carotid artery; atherosclerosis ID PERIPHERAL ARTERIAL-DISEASE; BLOOD-PRESSURE INDEX; INTIMA-MEDIA THICKNESS; B-MODE ULTRASOUND; HYPERTENSIVE ADULTS; GENERAL-POPULATION; VASCULAR-DISEASE; EDINBURGH ARTERY; ELDERLY WOMEN; PREVALENCE AB The resting ankle-brachial index (ABI) is a non-invasive method to assess the patency of the lower extremity arterial system and to screen for the presence of peripheral occlusive arterial disease. To determine how the ABI is associated with clinical coronary heart disease (CHD), stroke, preclinical carotid plaque and far wall intimal-medial thickness (IMT) of the carotid and popliteal arteries, we conducted analyses in 15 106 middle-aged adults from the baseline examination (1987-1989) of the Atherosclerosis Risk in Communities (ARIC) Study. The prevalence of clinical CHD, stroke/transient ischemic attack (TIA) and preclinical carotid plaque increased with decreasing ABI levels, particularly al those of < 0.90. Individuals with ABI < 0.90 were twice as likely to have prevalent CHD as those with ABI > 0.90 (age-adjusted odds ratio (OR) ranging from 2.2 (95% CI: 1.0-5.1) in African-American men to 3.3 (95% CI: 2.1-5.0) in white men). Men with ABI < 0.90 were more than four times as likely to have stroke/TIA as those with ABI > 0.90 (age-adjusted OR: 4.2 (95% CI: 1.8-9.5) in African-American men and 4.9 (95% CI: 2.6-9.0) in white men). In women the association was weaker and not statistically significant. Among those free of clinical cardiovascular disease, individuals with ABI less than or equal to 0.90 had statistically significantly higher prevalence of preclinical carotid plaque compared to those with ABI > 0.90 (age-adjusted ORs ranging from 1.5 (95% CI: 1.0-1.9) in white women to 2.6 (95% CI: 1.06.6) in african-american men). The ABI was also inversely associated with far wall IMT of the carotid arteries (in both men and women) and the popliteal arteries (in men only). The associations of ABI with clinical CHD, stroke, preclinical carotid plaque and IMT of the carotid and popliteal arteries were attenuated and often not statistically significant after further adjustment for LDL cholesterol, cigarette smoking, hypertension and diabetes. These data demonstrate that low ABI levels, particularly those of < 0.90, are indicative of generalized atherosclerosis. (C) 1997 Elsevier Science Ireland Ltd. C1 UNIV N CAROLINA,SCH PUBL HLTH,DEPT EPIDEMIOL,CHAPEL HILL,NC 27515. UNIV N CAROLINA,SCH PUBL HLTH,DEPT BIOSTAT,CHAPEL HILL,NC 27515. UNIV N CAROLINA,SCH MED,DIV CARDIOL,CHAPEL HILL,NC 27515. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,SCH MED,DEPT ENDOCRINOL & METAB,BALTIMORE,MD 21218. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55016, N01-HC-55018] NR 41 TC 315 Z9 336 U1 1 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD MAY PY 1997 VL 131 IS 1 BP 115 EP 125 DI 10.1016/S0021-9150(97)06089-9 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XB411 UT WOS:A1997XB41100015 PM 9180252 ER PT J AU Dearden, JC Barratt, MD Benigni, R Bristol, DW Combes, RD Cronin, MTD Judson, PN Payne, MP Richard, AM Tichy, M Worth, AP Yourick, JJ AF Dearden, JC Barratt, MD Benigni, R Bristol, DW Combes, RD Cronin, MTD Judson, PN Payne, MP Richard, AM Tichy, M Worth, AP Yourick, JJ TI The development and validation of expert systems for predicting toxicity - The report and recommendations of an ECVAM/ECB workshop (ECVAM workshop 24) SO ATLA-ALTERNATIVES TO LABORATORY ANIMALS LA English DT Editorial Material ID NATIONAL-TOXICOLOGY-PROGRAM; AUTOMATED STRUCTURE EVALUATION; IDENTIFYING CONTACT ALLERGENS; RODENT CARCINOGENICITY; CHEMICAL-STRUCTURE; 44 CHEMICALS; SALMONELLA MUTAGENICITY; BIOLOGICAL-ACTIVITY; SAFETY EVALUATION; BIOASSAYS C1 LIVERPOOL JOHN MOORES UNIV, SCH PHARM & CHEM, LIVERPOOL L3 3AF, MERSEYSIDE, ENGLAND. UNILEVER RES, ENVIRONM SAFETY LAB, SHARNBROOK MK44 1LQ, BEDS, ENGLAND. IST SUPER SANITA, I-00161 ROME, ITALY. NIEHS, NIH, RES TRIANGLE PK, NC 27709 USA. FRAME, NOTTINGHAM NG1 4EE, ENGLAND. HEATHER LEA, HARROGATE HG3 1TE, ENGLAND. HLTH & SAFETY LAB, SHEFFIELD S3 7HQ, S YORKSHIRE, ENGLAND. US EPA, NHEERL, RES TRIANGLE PK, NC 27711 USA. NATL INST PUBL HLTH, PREDICT TOXICOL LAB, PRAGUE 10042 10, CZECH REPUBLIC. US FDA, COSMET TOXICOL BRANCH, LAUREL, MD 20708 USA. RP Dearden, JC (reprint author), COMMISS EUROPEAN COMMUNITIES, JOINT RES CTR, INST ENVIRONM, ECVAM, TP 580, I-21020 ISPRA, VA, ITALY. NR 79 TC 96 Z9 97 U1 1 U2 1 PU FRAME PI NOTTINGHAM PA RUSSELL & BURCH HOUSE 96-98 NORTH SHERWOOD ST, NOTTINGHAM NG1 4EE, NOTTS, ENGLAND SN 0261-1929 J9 ATLA-ALTERN LAB ANIM JI ATLA-Altern. Lab. Anim. PD MAY-JUN PY 1997 VL 25 IS 3 BP 223 EP 252 PG 30 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XC771 UT WOS:A1997XC77100009 ER PT J AU Lalwani, AK Linthicum, FH Wilcox, ER Moore, JK Walters, FC SanAgustin, TB Mislinski, J Miller, MR Sinninger, Y Attaie, A Luxford, WM AF Lalwani, AK Linthicum, FH Wilcox, ER Moore, JK Walters, FC SanAgustin, TB Mislinski, J Miller, MR Sinninger, Y Attaie, A Luxford, WM TI A five-generation family with late-onset progressive hereditary hearing impairment due to cochleosaccular degeneration SO AUDIOLOGY AND NEURO-OTOLOGY LA English DT Article DE Scheibe degeneration; linkage analysis; lod score; temporal-bone histopathology ID TEMPORAL BONE FINDINGS; NON-SYNDROMIC DEAFNESS; WAARDENBURG SYNDROME; INNER-EAR; 2 FAMILIES; GENE; LINKAGE; MUTATIONS; MOUSE; MAPS AB Cochleosaccular dysplasia or degeneration (Scheibe degeneration) is considered the most common cause of profound congenital hearing impairment, and accounts for approximately 70% of cases 2 with hereditary deafness. A five-generation family with hereditary hearing impairment associated with cochleosaccular degeneration has recently been identified. The diagnosis of classical Scheibe degeneration was based on histopathological findings in the temporal bones of the proband, a 61-year-old profoundly deaf male. Auditory structures in the brainstem of the proband were also studied. Twenty-two members of the family were contacted for surveys and blood samples. Of these, 6 males and 2 females have hearing impairment. Complete audiological evaluation was done on 12 family members, and prior audiologic records of the proband and affected family members were available for study. Affected family members suffer a mild bilateral high-frequency hearing loss during childhood and adolescence, and progress to moderate-to-profound deafness in the second and third decades of life. The family is suitable for Linkage analysis and does not map to previously reported loci harboring autosomal dominant, nonsyndromic hereditary hearing impairment genes. The genetic study of this family will be helpful in identifying the genes which, when mutated, result in Scheibe degeneration. C1 HOUSE EAR RES INST,DEPT HISTOPATHOL,LOS ANGELES,CA. HOUSE EAR RES INST,DEPT NEUROANAT,LOS ANGELES,CA. HOUSE EAR RES INST,DEPT CHILDRENS AUDITORY RES & EVALUAT,LOS ANGELES,CA. HOUSE EAR CLIN,LOS ANGELES,CA. NIDOCD,GENET MOL LAB,NIH,ROCKVILLE,MD. RP Lalwani, AK (reprint author), UNIV SAN FRANCISCO,DEPT OTOLARYNGOL HEAD & NECK SURG,MOL OTOL LAB,350 PARNASSUS AVE,SUITE 210,SAN FRANCISCO,CA 94117, USA. NR 43 TC 25 Z9 25 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-3030 J9 AUDIOL NEURO-OTOL JI Audiol. Neuro-Otol. PD MAY-JUN PY 1997 VL 2 IS 3 BP 139 EP 154 PG 16 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA WR094 UT WOS:A1997WR09400003 PM 9390828 ER PT J AU Colton, C OsterGranite, M Chernyshev, O Snell, J Behar, T Gbadegesin, O Gilbert, D AF Colton, C OsterGranite, M Chernyshev, O Snell, J Behar, T Gbadegesin, O Gilbert, D TI Oxidative changes in trisomy 16 mice as a model of Down syndrome and Alzheimer's disease SO BEHAVIOR GENETICS LA English DT Meeting Abstract C1 GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. UNIV CALIF RIVERSIDE,RIVERSIDE,CA 92521. NINCDS,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 MAY PY 1997 VL 27 IS 3 BP 260 EP 260 PG 1 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA XG232 UT WOS:A1997XG23200013 ER PT J AU Richert, JR Grekova, MC Robinson, ED McFarland, HF AF Richert, JR Grekova, MC Robinson, ED McFarland, HF TI Deficient expression of the inhibitory transcription factor Sp3 in multiple sclerosis immune cells. SO BEHAVIOR GENETICS LA English DT Meeting Abstract C1 GEORGETOWN UNIV,MED CTR,SCH MED,WASHINGTON,DC 20007. NINCDS,NEUROIMMUNOL BRANCH,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 MAY PY 1997 VL 27 IS 3 BP 264 EP 264 PG 1 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA XG232 UT WOS:A1997XG23200028 ER PT J AU Palumbo, A DiCosmo, A Gesualdo, I Hearing, VJ AF Palumbo, A DiCosmo, A Gesualdo, I Hearing, VJ TI Subcellular localization and function of melanogenic enzymes in the ink gland of Sepia officinalis SO BIOCHEMICAL JOURNAL LA English DT Article ID TYROSINASE-RELATED PROTEIN; DOPACHROME CONVERSION FACTOR; II OCULOCUTANEOUS ALBINISM; MOUSE TYROSINASE; METAL-IONS; LOCUS; GENE; CDNA; MAPS; IDENTIFICATION AB The ink gland of the cuttlefish Sepia officinalis has traditionally been regarded as a convenient model system for investigating melanogenesis. This gland has been shown to contain a variety of melanogenic enzymes including tyrosinase, a dopachrome-rearranging enzyme and peroxidase. However, whether and to what extent these enzymes co-localize in the melanogenic compartments and interact is an open question. Using polyclonal antibodies that recognize the corresponding Sepia proteins, we have been able to demonstrate that peroxidase has a different subcellular localization pattern from tyrosinase and dopachrome-rearranging enzyme. Whereas peroxidase is located in the rough endoplasmic reticulum and in the matrix of premelanosomes and melanosomes, tyrosinase and dopachrome-rearranging enzyme are present in the rough endoplasmic reticulum-Golgi transport system, at the level of trans-Golgi cisternae, trans-Golgi network and coated vesicles, and in melanosomes on pigmented granules. These results fill a longstanding gap in our knowledge of the melanin-producing system in Sepia and provide the necessary background for dissection at the molecular level of the complex interaction between melanogenic enzymes. Moreover, the peculiar and complex organization of melanin in an invertebrate such as Sepia officinalis is surprising and could provide the basis for understanding the process in more evolved systems such as that of mammals. C1 UNIV NAPLES FEDERICO II, DEPT ZOOL, NAPLES, ITALY. NCI, CELL BIOL LAB, BETHESDA, MD 20892 USA. RP Palumbo, A (reprint author), Staz Zool Anton Dohrn, BIOCHEM & MOL BIOL LAB, VILLA COMUNALE, I-80121 NAPLES, ITALY. OI Di Cosmo, Anna/0000-0002-1018-9957 NR 49 TC 28 Z9 30 U1 0 U2 3 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAY 1 PY 1997 VL 323 BP 749 EP 756 PN 3 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WZ258 UT WOS:A1997WZ25800022 PM 9169609 ER PT J AU Wolffe, AP AF Wolffe, AP TI Histones, nucleosomes and the role of chromatin structure in transcriptional control SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT 660th Meeting Biochemical-Society / British-Society-Immunology CY DEC 10-13, 1996 CL HARROGATE, ENGLAND SP Biochem Soc, Brit Soc Immunol ID RIBOSOMAL-RNA GENE; ACETYLATION; DNA; CORE; PROMOTER; BINDING; DOMAIN; YEAST RP Wolffe, AP (reprint author), NIH,MOL EMBRYOL LAB,BETHESDA,MD 20892, USA. NR 22 TC 16 Z9 17 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 MAY PY 1997 VL 25 IS 2 BP 354 EP 358 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XB637 UT WOS:A1997XB63700002 PM 9191116 ER PT J AU Wolffe, AP Wong, J Li, Q Levi, BZ Shi, YB AF Wolffe, AP Wong, J Li, Q Levi, BZ Shi, YB TI Three steps in the regulation of transcription by the thyroid hormone receptor: Establishment of a repressive chromatin structure, disruption of chromatin and transcriptional activation SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT 660th Meeting Biochemical-Society / British-Society-Immunology CY DEC 10-13, 1996 CL HARROGATE, ENGLAND SP Biochem Soc, Brit Soc Immunol ID RETINOIC ACID; NUCLEAR RECEPTORS; RESPONSE ELEMENT; GENE; BETA RP Wolffe, AP (reprint author), NICHHD,MOL EMBRYOL LAB,NIH,BLDG 18T,ROOM 106,BETHESDA,MD 20892, USA. NR 18 TC 11 Z9 11 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 MAY PY 1997 VL 25 IS 2 BP 612 EP 615 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XB637 UT WOS:A1997XB63700052 PM 9191166 ER PT J AU Denkers, EY Sher, A AF Denkers, EY Sher, A TI Role of natural killer and NK1(+) T-cells in regulating cell-mediated immunity during Toxoplasma gondii infection SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT 660th Meeting Biochemical-Society / British-Society-Immunology CY DEC 10-13, 1996 CL HARROGATE, ENGLAND SP Biochem Soc, Brit Soc Immunol ID PROMPTLY PRODUCE INTERLEUKIN-4; CD8+ LYMPHOCYTES-T; II-DEFICIENT MICE; IFN-GAMMA; INTERFERON-GAMMA; RESISTANCE; CD4(+); CD4+; INDUCTION; RESPONSES C1 NIAID,IMMUNOL SECT,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. RP Denkers, EY (reprint author), CORNELL UNIV,COLL VET MED,DEPT MICROBIOL & IMMUNOL,ITHACA,NY 14853, USA. NR 43 TC 11 Z9 13 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 MAY PY 1997 VL 25 IS 2 BP 699 EP 703 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XB637 UT WOS:A1997XB63700072 PM 9191186 ER PT J AU Mansfield, E Chiron, MF Amlot, P Pastan, I FitzGerald, DJ AF Mansfield, E Chiron, MF Amlot, P Pastan, I FitzGerald, DJ TI Recombinant RFB4 single-chain immunotoxin that is cytotoxic towards CD22-positive cells SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT 660th Meeting Biochemical-Society / British-Society-Immunology CY DEC 10-13, 1996 CL HARROGATE, ENGLAND SP Biochem Soc, Brit Soc Immunol ID HUMAN B-CELLS; PSEUDOMONAS EXOTOXIN; INVIVO THERAPY; CD22; ANTIBODIES; RICIN C1 NCI,MOL BIOL LAB,DBS,NIH,BETHESDA,MD 20892. ROYAL FREE HOSP,DEPT IMMUNOL,LONDON NW3 2PF,ENGLAND. NR 11 TC 23 Z9 23 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 MAY PY 1997 VL 25 IS 2 BP 709 EP 714 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XB637 UT WOS:A1997XB63700074 PM 9191188 ER PT J AU John, CS Lim, BB Geyer, BC Vilner, BJ Bowen, WD AF John, CS Lim, BB Geyer, BC Vilner, BJ Bowen, WD TI Tc-99m-labeled sigma-receptor-binding complex: Synthesis, characterization, and specific binding to human ductal breast carcinoma (T47D) cells SO BIOCONJUGATE CHEMISTRY LA English DT Article ID H-3 (+)-PENTAZOCINE; AFFINITY; TECHNETIUM; RHENIUM; LIGAND; POTENT; TUMORS; AGENTS; BRAIN AB sigma-Receptors have recently been shown to be expressed in a variety of human tumor cells. In an attempt to prepare Tc-99m chelates that would bind to sigma-receptors and be useful. for imaging sigma-receptor-positive tumors, we have synthesized and characterized a bisaminothiol (BAT) chelate appended with a sigma-receptor pharmacophore. The synthesis of target ligand VII was accomplished in three steps starting from bicyclic imidazolidino[1,2-d]dithiazapine. The labeling of the BAT ligand with Tc-99m was carried out in high yields (> 80%) using stannous tartarate as a reducing agent, resulting in the target sigma-receptor-binding chelate [Tc-99m]BAT-EN6, III. Similarly, Tc-99g chelate with ligand VII was prepared from ammonium pertechnetate by reduction with stannous tartarate. Tc-99m-radiolabeled chelate was purified by reversed phase HPLC, and cell binding with human breast ductal carcinoma (T47D) was performed. A high degree of specific binding (90-97%) was obtained when sigma-receptor ligands such as halogenated phenylethylenediamines were used to determine nonspecific binding. A modest affinity dose-dependent inhibition of binding was found with BD1008, I, and 4-IPEMP, II (IC50 = 47 +/- 2 and 59 +/- 5 nM, respectively), known sigma-ligands. No specific binding was found with [Tc-99m]BAT, VIII [without appended sigma-pharmacophore (N-alkyl-substituted ethylenediamine)], showing that biological activity resulted from the pendent pharmacophore. (TC)-T-99g complex was found to be a potent inhibitor (K-i = 42.7 +/- 8.5 nM) of [H-3]DTG binding in guinea pig brain membranes. Scatchard analysis of [Tc-99m]BAT-EN6 (spiked with [Tc-99m]BAT-EN6) binding in T47D breast cancer cells showed a saturable binding, with a K-d of 43.5 +/- 14.7 nM and a B-max of 3121 +/- 130 fmol/(mg of protein). A biodistribution study of [Tc-99m]BAT-EN6 chelates in Sprague Dawley rats showed hepatic clearance, as expected. A blocking study at 4 h postinjection using 2 mu mol of BD1008 with [Tc-99m]BAT-EN6 showed a significant decrease of radiopharmaceutical in liver (15.3 vs 22.31% ID/organ) and kidney (1.01 vs 2.21% ID/organ), organs known to possess high concentrations of sigma-receptors. These results imply that [Tc-99m]-BAT-EN6 binds with high affinity to sigma-receptors expressed in human breast tumor cells, and it may be useful for imaging breast cancer. C1 NIDDK,MED CHEM LAB,UNIT RECEPTOR BIOCHEM & PHARMACOL,NIH,BETHESDA,MD 20892. RP John, CS (reprint author), GEORGE WASHINGTON UNIV,MED CTR,DEPT RADIOL,RADIOPHARMACEUT CHEM SECT,661 ROSS HALL,2300 I ST NW,WASHINGTON,DC 20037, USA. NR 26 TC 26 Z9 29 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAY-JUN PY 1997 VL 8 IS 3 BP 304 EP 309 DI 10.1021/bc9700087 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA XB627 UT WOS:A1997XB62700007 PM 9177835 ER PT J AU Wu, CC Jagoda, E Brechbiel, M Webber, KO Pastan, I Gansow, O Eckelman, WC AF Wu, CC Jagoda, E Brechbiel, M Webber, KO Pastan, I Gansow, O Eckelman, WC TI Biodistribution and catabolism of Ga-67-labeled anti-Tac dsFv fragment SO BIOCONJUGATE CHEMISTRY LA English DT Article ID DISULFIDE-STABILIZED FV; MOLECULAR-WEIGHT PROTEINS; FILTRATION; TRANSPORT; ACID AB The disulfide-linked fragment (dsFv) of the antibody to the a subunit of the IL2 receptor has been radiolabelled with a [Ga-67] Ga-2-(p-SCN-Bz)-NOTA derivative linked through an isothiocyanato group to either the E-amino group of lysine or the a-amino group of the N-terminal amino acids. This low molecular weight protein (LMWP) has been proposed as a tumor diagnostic agent. However, >60% of the injected dose localized in the mouse kidney. The major catabolites (>95%) in the kidney were identified as the Ga-2-(p-SCN-Bz)-NOTA conjugate with either lysine or methionine, with no evidence of transchelation of Ga-67. Since different amino acids in the dsFv were radiolabelled according to this procedure, it was possible to study the relative residence times of the various catabolites. The methionine conjugate had a significantly shorter residence time than the lysine conjugate in the same kidney. Labelling the appropriate amino acid in a LMWP may lead to reduced residence times and increased diagnostic or therapeutic ratios. C1 NCI, DIV CANC BIOL, MOL BIOL LAB, RADIAT ONCOL BRANCH, BETHESDA, MD 20892 USA. NIH, CTR CLIN, POSITRON EMISS TOMOG DEPT, BETHESDA, MD 20892 USA. NR 20 TC 38 Z9 38 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAY-JUN PY 1997 VL 8 IS 3 BP 365 EP 369 DI 10.1021/bc970032k PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA XB627 UT WOS:A1997XB62700014 PM 9177842 ER PT J AU Yasuzawa, T Tomer, KB AF Yasuzawa, T Tomer, KB TI Structural determination of the conjugate of human serum albumin with a mitomycin C derivative, KW-2149, by matrix-assisted laser desorption/ionization mass spectrometry SO BIOCONJUGATE CHEMISTRY LA English DT Article ID DRUG BINDING-SITES; COVALENT BINDING; DESORPTION IONIZATION; LIQUID-CHROMATOGRAPHY; ANTITUMOR-ACTIVITY; ACYL GLUCURONIDES; IN-VITRO; REACTIVITY; IDENTIFICATION; ACTIVATION AB new mitomycin C derivative, KW-2149, is known to form a covalent conjugate with human serum albumin (HSA). This conjugate exhibits 1/20 of the anticellular activity of unconjugated KW-2149. Structural studies of this conjugate were carried out using a combination of enzymatic digestion, high-performance liquid chromatography (HPLC), and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. The tryptic peptide T5 (residues 21-41) was the only peptide found to be modified by KW-2149 moieties, the [(gamma-L-glutamylamino)ethyl]thio group or the (2-aminoethyl)thio group, through a disulfide bond. Although the latter peptide lost its mitomycin C moiety in the course of tryptic digestion, these data strongly suggest that KW-2149 was bound to Cys-34, the only free cysteine on KSA. C1 NIEHS,STRUCT BIOL LAB,RES TRIANGLE PK,NC 27709. RI Tomer, Kenneth/E-8018-2013 NR 35 TC 16 Z9 16 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAY-JUN PY 1997 VL 8 IS 3 BP 391 EP 399 DI 10.1021/bc970038+ PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA XB627 UT WOS:A1997XB62700018 PM 9177846 ER PT J AU Frey, A Neutra, MR Robey, FA AF Frey, A Neutra, MR Robey, FA TI Peptomer aluminum oxide nanoparticle conjugates as systemic and mucosal vaccine candidates: Synthesis and characterization of a conjugate derived from the C4 domain of HIV-1(MN) gp120 SO BIOCONJUGATE CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; MONOCLONAL-ANTIBODIES; AFFINITY-CHROMATOGRAPHY; CONTAINING PEPTIDES; CYCLIC-PEPTIDES; AMINO-ACID; IDENTIFICATION; GLYCOPROTEIN; RECEPTOR; ADJUVANT AB Peptomers are polymers composed of peptides that are specifically cross-linked in a head-to-tail fashion. Recently, a peptomer composed of an amphipathic peptide from the C4 domain of HIV-1(MN) gp120 was shown to display a prominent alpha-helical conformation that, as an immunogen, elicited rabbit antibodies recognizing native and recombinant gp120 [Robey et al. (1995) J. Biol. Chem. 270, 23918-23921]. For the present study, we synthesized a conjugate composed of the C4 peptomer covalently linked to calcinated aluminum oxide nanoparticles. The nanoparticles were first reacted with (3-aminopropyl)-triethoxysilane to provide an amine load of 15.9 mmol of R-NH2/g of solid. The amine-modified aluminum oxide nanoparticles then were reacted with N-acetylhomocysteine thiolactone at pH 10 to place a reactive thiol on the nanoparticles. A bromoacetylated C4 peptomer, modified at the E-amines of lysine residues, then was reacted with the thiolated nanoparticles to give the peptomer covalently linked to aluminum oxide via a thioether bond. The peptomer load was determined to be 16 mg of peptomer/g of particles, a 55% theoretical yield. Particle shape and size of the peptomer-conjugated alumina were analyzed by electron microscopy and displayed a mean maximum diameter of 355 nm and a mean minimum diameter of 113 nm, well within the desired size range of 300 nm believed to be optimal for mucosal immunization purposes. Experimentally determined values of mean particle diameters, specific surface area, and specific peptomer load provided the information necessary to calculate the mean antigen load, which was determined to be 53 000 +/- 42 000 peptomer epitopes per particle. Peptomer-alumina conjugates, such as that described here, could form the basis of a new class of biomaterial that combines a chemically defined organic immunogen with a nontoxic chemically defined inorganic adjuvant. C1 NIDR,ORAL & PHARYNGEAL CANC BRANCH,NIH,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. CHILDRENS HOSP,GI CELL BIOL RES LAB,BOSTON,MA 02115. FU NIAID NIH HHS [AI34757]; NICHD NIH HHS [HD17557]; NIDDK NIH HHS [DK-34854] NR 54 TC 36 Z9 36 U1 1 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAY-JUN PY 1997 VL 8 IS 3 BP 424 EP 433 DI 10.1021/bc970036p PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA XB627 UT WOS:A1997XB62700022 PM 9177850 ER PT J AU Rizzo, LV Whitcup, SM Nussenblatt, RB AF Rizzo, LV Whitcup, SM Nussenblatt, RB TI Autoimmune ocular disorders - Current status of oral tolerance therapy SO BIODRUGS LA English DT Article ID MYELIN BASIC-PROTEIN; IMMUNE-RESPONSES; LYMPHOCYTES-T; II COLLAGEN; INDUCTION; ANTIGEN; SUPPRESSION; ENCEPHALOMYELITIS; MECHANISMS; REJECTION AB The ability of orally presented antigen to induce a state of tolerance has been recognised for many years. The use of this immunological phenomenon of oral tolerance to treat autoimmune diseases is a more recent development in the field of mucosal immunology. Ocular autoimmunity is especially intriguing because of the unique immunological characteristics of the eye. On the basis of laboratory data, the 'feeding' of ocular antigens has been proposed as a safe and efficacious therapy for uveitis. Two patients with uveitis have been successfully treated with oral administration of retinal S-antigen, and a larger phase I/II trial of oral tolerance as a treatment for uveitis is currently being completed at the National Eye Institute. C1 NEI,CLIN BRANCH,NIH,BETHESDA,MD 20892. RP Rizzo, LV (reprint author), NEI,IMMUNOL LAB,NIH,BLDG 10,ROOM 10N202,10 CTR DR,BETHESDA,MD 20892, USA. RI Rizzo, Luiz Vicente/B-4458-2009 NR 37 TC 0 Z9 0 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1173-8804 J9 BIODRUGS JI Biodrugs PD MAY PY 1997 VL 7 IS 5 BP 335 EP 340 DI 10.2165/00063030-199707050-00001 PG 6 WC Oncology; Immunology; Pharmacology & Pharmacy SC Oncology; Immunology; Pharmacology & Pharmacy GA WY236 UT WOS:A1997WY23600001 PM 18031097 ER PT J AU Park, MH Lee, YB Joe, YA AF Park, MH Lee, YB Joe, YA TI Hypusine is essential for eukaryotic cell proliferation SO BIOLOGICAL SIGNALS LA English DT Article DE hypusine; deoxyhypusine; eukaryotic initiation-factor 5A; posttranslational modification; proliferation; spermidine; polyamine ID TRANSLATION INITIATION-FACTOR; HUMAN DEOXYHYPUSINE SYNTHASE; YEAST SACCHAROMYCES-CEREVISIAE; AMINO-ACID; CONTAINING PROTEIN; SEQUENCE DETERMINATION; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; AEROBIC GROWTH; FACTOR EIF-5A AB Hypusine [N-epsilon-(4-amino-2-hydroxybutyl)lysine] occurs in all eukaryotes at one residue in a highly conserved protein, the putative eukaryotic translation initiation factor 5A (eIF-5A, old terminology eIF-4D). This unusual amino acid is produced in a unique posttranslational modification reaction that involves the conjugation of the 4-aminobutyl moiety of the polyamine spermidine to the epsilon-amino group of a specific lysine residue of the eIF-5A precursor protein to form the deoxyhypusine [N-epsilon-(4-aminobutyl)lysine] residue and its subsequent hydroxylation. The strict specificity of hypusine synthesis, its derivation from spermidine and its requirement for the activity of eIF-5A and for eukaryotic cell proliferation have raised keen interest in the physiological function of the hypusine-containing protein, eIF-5A. RP Park, MH (reprint author), NIDR,NIH,ORAL & PHARYNGEAL CANC BRANCH,BLDG 30,ROOM 211,BETHESDA,MD 20892, USA. NR 47 TC 160 Z9 168 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1016-0922 J9 BIOL SIGNAL JI Biol. Signals PD MAY-JUN PY 1997 VL 6 IS 3 BP 115 EP 123 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XV331 UT WOS:A1997XV33100003 PM 9285094 ER PT J AU Newbold, RR Hanson, RB Jefferson, WN AF Newbold, RR Hanson, RB Jefferson, WN TI Ontogeny of lactoferrin in the developing mouse uterus: A marker of early hormone response SO BIOLOGY OF REPRODUCTION LA English DT Article ID REPRODUCTIVE-TRACT; ESTROGEN-RECEPTOR; PRENATAL EXPOSURE; LACTOTRANSFERRIN GENE; DIETHYLSTILBESTROL; EXPRESSION; MICE; SENSITIVITY; PROTEIN; CYCLE AB Lactoferrin (LF) was mapped during organogenesis of the murine reproductive tract, starting on fetal Day 12, as a marker of estrogen responsiveness. To induce LF expression, pregnant outbred CD-1 mice were injected s.c. with diethylstilbestrol (DES; 100 mu g/kg maternal body weight), and fetal genital tract tissues were removed; neonatal and immature mice received s.c. injections of DES (2 mu g/pup per day). Corn oil-treated and untreated mice at corresponding ages provided the controls. Immunocytochemical techniques using a polyclonal antibody showed no detectable LF in control genital tract tissues until late gestation. However, after DES treatment, LF was localized in uterine epithelial cells as early as fetal Day 14; the intensity of LF staining increased with age and number of DES treatments. Control uterine tissues responded to the rise of circulating estrogens at parturition (fetal Day 19) by producing LF, although the magnitude of response was lower than that of DES-treated tissues. Uterine tissue homogenates from control and DES mice were analyzed by SDS-PAGE and Western blots, verifying the protein to be LF. Isolation of mRNA and Northern blot analysis further showed that LF mRNA was present in the developing Mullerian duct and that DES stimulated early induction of the LF gene. The early appearance of LF suggests that it may play an important role in the hormonal regulation of growth and differentiation of developing uterine tissues. RP Newbold, RR (reprint author), NIEHS,DEV ENDOCRINOL SECT,REPROD TOXICOL GRP,LAB TOXICOL,ENVIRONM TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709, USA. NR 57 TC 31 Z9 31 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD MAY PY 1997 VL 56 IS 5 BP 1147 EP 1157 DI 10.1095/biolreprod56.5.1147 PG 11 WC Reproductive Biology SC Reproductive Biology GA WV691 UT WOS:A1997WV69100011 PM 9160713 ER PT J AU Morris, TS Frormann, S Shechosky, S Lowe, C Lall, MS GaussMuller, V Purcell, RH Emerson, SU Vederas, JC Malcolm, BA AF Morris, TS Frormann, S Shechosky, S Lowe, C Lall, MS GaussMuller, V Purcell, RH Emerson, SU Vederas, JC Malcolm, BA TI In vitro and ex vivo inhibition of hepatitis A virus 3C proteinase by a peptidyl monofluoromethyl ketone SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID A VIRUS; SERINE PROTEINASES; FLUOROMETHYL KETONES; CYSTEINE PROTEINASES; BINDING; CHYMOTRYPSIN; INACTIVATION; ANALOGS; PAPAIN; CHLOROKETONES AB Hepatitis A virus (HAV) 3C proteinase is the enzyme responsible for the processing of the viral polyprotein. Although a cysteine proteinase, it displays an active site configuration like those of the mammalian serine proteinases (Malcolm, B. A. Protein Science 1995, 4, 1439). A peptidyl monofluoromethyl ketone (peptidyl-FMK) based on the preferred peptide substrates for HAV 3C proteinase was generated by first coupling the precursor, N,N-dimethylglutamine fluoromethylalcohol, to the tripeptide, Ac-Leu-Ala-Ala-OH, and then oxidizing the product to the corresponding peptidyl-FMK (Ac-LAAQ'-FMK). This molecule was found to be an irreversible inactivator of HAV 3C with a second-order rate constant of 3.3 x 10(2) M-1 s(-1). F-19 NMR spectroscopy indicates the displacement of fluoride on inactivation of the enzyme by the fluoromethyl ketone. NMR spectroscopy of the complex between the C-13-labeled inhibitor and the HAV 3C proteinase indicates that an (alkylthio)methyl ketone is formed. Studies of polyprotein processing, using various substrates generated by in vitro transcription/translation, demonstrated efficient blocking of even the most rapid proteolytic events such as cleavage of the 2A-2B and 2C-3A junctions. Subsequent ex vivo studies, to test for antiviral activity, show a 25-fold reduction in progeny virus production as the result of treatment with 5 mu M inhibitor 24 h postinfection. (C) 1997 Elsevier Science Ltd. C1 UNIV ALBERTA,DEPT CHEM,EDMONTON,AB T6G 2G2,CANADA. UNIV ALBERTA,DEPT BIOCHEM,EDMONTON,AB T6G 2H7,CANADA. UNIV LUBECK,INST MED MICROBIOL,D-23538 LUBECK,GERMANY. RP Morris, TS (reprint author), NIAID,HEPATITIS VIRUSES SECT,NIH,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [AI 38249] NR 37 TC 24 Z9 24 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD MAY PY 1997 VL 5 IS 5 BP 797 EP 807 DI 10.1016/S0968-0896(97)88649-X PG 11 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA XE718 UT WOS:A1997XE71800002 PM 9208091 ER PT J AU Chordia, MD Kingston, DGI Hamel, E Lin, CM Long, BH Fairchild, CA Johnston, KA Rose, WC AF Chordia, MD Kingston, DGI Hamel, E Lin, CM Long, BH Fairchild, CA Johnston, KA Rose, WC TI Synthesis and biological activity of A-nor-paclitaxel analogues SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID MODIFIED TAXOLS AB A number of paclitaxel analogues with a 5-membered A-ring (A-nor-paclitaxels, or (15 right-arrow 1)-abeo-paclitaxels) have been prepared in order to determine whether analogues of this class might have improved bioactivity as compared with paclitaxel. Most of the compounds synthesized were less active than paclitaxel, but one analogue was equivalent to paclitaxel in a tubulin-assembly assay, and another analogue was more cytotoxic than paclitaxel in two different cell lines of the NCI screen. C1 NCI,FREDERICK CANC RES & DEV CTR,LAB DRUG DISCOVERY RES & DEV,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,PRINCETON,NJ 08543. RP Chordia, MD (reprint author), VIRGINIA POLYTECH INST & STATE UNIV,DEPT CHEM,BLACKSBURG,VA 24061, USA. RI Chordia, Mahendra/A-4706-2008; OI Kingston, David/0000-0001-8944-246X FU NCI NIH HHS [CA 55131] NR 13 TC 17 Z9 17 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD MAY PY 1997 VL 5 IS 5 BP 941 EP 947 DI 10.1016/S0968-0896(97)00035-7 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA XE718 UT WOS:A1997XE71800014 PM 9208103 ER PT J AU Figg, WD Christian, MC Lush, R Link, CJ Davis, P Kohn, E Sarosy, G Rothenberg, ML Weiss, RB Ryan, N Jacobs, J Reed, E AF Figg, WD Christian, MC Lush, R Link, CJ Davis, P Kohn, E Sarosy, G Rothenberg, ML Weiss, RB Ryan, N Jacobs, J Reed, E TI Pharmacokinetics of elemental platinum (ultrafiltrate and total) after a thirty minute intravenous infusion of ormaplatin SO BIOPHARMACEUTICS & DRUG DISPOSITION LA English DT Article DE pharmacokinetics; ormaplatin; ultrafiltrate; AAS, phase 1 ID I CLINICAL-TRIAL; PHASE-I; CISPLATIN; TETRAPLATIN; CARBOPLATIN; RESISTANCE; NSC-363812; REDUCTION; ANALOGS AB Preclinical data suggest that ormaplatin (tetrachloro-(d1-trans)-1,2-diamminocyclohexaneplatinum) has substantial activity in cisplatin-resistant tumor models and may be less nephrotoxic than cisplatin. Based on these data we initiated a phase I clinical trial in patients with refractory metastatic cancer. This report characterizes the pharmacokinetic profile of both the total plasma concentrations of elemental platinum and the unbound ultrafiltrate concentrations of elemental platinum, following a 30 min intravenous infusion of ormaplatin. Platinum concentrations were determined by AAS, and pharmacokinetic parameters for both the total plasma concentration and the ultrafiltrate concentration of elemental platinum were determined using both compartmental and noncompartmental methods. Twenty-eight patients (14 males and 14 females; median age, 58) received ormaplatin. There was a linear relationship between C-max and dose (r(2)=0.945) and AUC and dose (r(2)=0.976). Ormaplatin is more accurately described by a two-compartment model than by a one-compartment model. The distribution half-life (t(1/2 alpha)) was 0.3 h and the terminal half-life (t(1/2 beta)) was 39.1 h. The volume of the central compartment (V) was 68.6 L and the volume of distribution at steady state (V-dss) was 183 L. Like total plasma platinum, unbound platinum is also best characterized by a two-compartment model. The elimination of free platinum is also biphasic with a distribution half-life (t(1/2 alpha)) of 0.3 h and a terminal half-life (t(1/2 beta)) of 19.3 h. The mean volume of the central compartment (V) was 200.5 L, and the mean volume of distribution at steady state (V-dss) was 560.5 L. Clinical development of ormaplatin has been terminated due to increased frequency of neurological complications noted over other platinum agents; however, the pharmacokinetics are, in general, similar to those of other clinically used platinum compounds. (C) 1997 by John Wiley & Sons, Ltd. RP Figg, WD (reprint author), NCI,CLIN PHARMACOKINET SECT,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,CLIN PHARMACOL BRANCH,NIH,BETHESDA,MD 20892, USA. RI Figg Sr, William/M-2411-2016 NR 22 TC 5 Z9 5 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0142-2782 J9 BIOPHARM DRUG DISPOS JI Biopharm. Drug Dispos. PD MAY PY 1997 VL 18 IS 4 BP 347 EP 359 DI 10.1002/(SICI)1099-081X(199705)18:4<347::AID-BDD23>3.0.CO;2-O PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WY322 UT WOS:A1997WY32200006 PM 9158882 ER PT J AU Frisbie, SM Chalovich, JM Brenner, B Yu, LC AF Frisbie, SM Chalovich, JM Brenner, B Yu, LC TI Modulation of cross-bridge affinity for MgGTP by Ca2+ in skinned fibers of rabbit psoas muscle SO BIOPHYSICAL JOURNAL LA English DT Article ID ADENOSINE 5'-TRIPHOSPHATE; TROPONIN-TROPOMYOSIN; MYOSIN SUBFRAGMENT-1; PARALLEL INHIBITION; FORCE GENERATION; RELAXED MUSCLE; IONIC-STRENGTH; ACTIVE FORCE; BINDING; STIFFNESS AB Previously we reported that saturation of cross-bridges with MgATP gamma S in skinned muscle fibers was calcium sensitive. In the present study we investigate whether this observation can be generalized to other nucleotides by studying saturation of cross-bridges with MgGTP. In solution, myosin-subfragment 1 (S1) in the presence of 10 mM MgGTP was found to bind to actin with low affinity, similar to that in the presence of MgATP and MgATP gamma S, In EGTA buffer, the equatorial x-ray diffraction intensity ratio l(11)/l(10) recorded in single skinned fibers decreased upon increasing MgGTP concentration from 0 to 10 mM (1 degrees C and 170 mM ionic strength), The I-11/l(10) ratio leveled off at 10 mM MgGTP, indicating full saturation of cross-bridges with the nucleotide. Under these conditions, the value of l(11)/l(10) is indistinguishable from that obtained in the presence of saturating [MgATP]. In CaEGTA buffer, however, the decrease in l(11)/l(10) occurs over a wider range of concentrations, and there is no indication of l(11)/l(10) leveling off at 10 mM MgGTP, suggesting that full saturation is not reached. The Ca2+ dependence of GTP binding appears to be a direct consequence of the differences in the affinities of the strongly bound cross-bridges to actin versus weakly bound cross-bridges to actin, A biochemical scheme that could qualitatively explain the titration behavior of ATP gamma S and GTP is presented. C1 NIAMSD,NIH,BETHESDA,MD 20892. E CAROLINA UNIV,SCH MED,GREENVILLE,NC 27834. HANNOVER MED SCH,KLIN PHYSIOL,HANNOVER,GERMANY. OI Chalovich, Joseph/0000-0002-1243-4055 FU NIAMS NIH HHS [AR35126] NR 30 TC 6 Z9 6 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 MAY PY 1997 VL 72 IS 5 BP 2255 EP 2261 PG 7 WC Biophysics SC Biophysics GA WV984 UT WOS:A1997WV98400033 PM 9129828 ER PT J AU Bosco, MC Rottschafer, S Taylor, LS Ortaldo, JR Longo, DL EspinozaDelgado, I AF Bosco, MC Rottschafer, S Taylor, LS Ortaldo, JR Longo, DL EspinozaDelgado, I TI The antineoplastic agent bryostatin-1 induces proinflammatory cytokine production in human monocytes: Synergy with interleukin-2 and modulation of interleukin-2R gamma chain expression SO BLOOD LA English DT Article ID PROTEIN-KINASE-C; TUMOR-NECROSIS-FACTOR; ACTIVATOR BRYOSTATIN-1; PHORBOL ESTERS; GAMMA-CHAIN; MACROCYCLIC LACTONE; ANTITUMOR-ACTIVITY; ANTICANCER AGENT; INTERFERON-GAMMA; BLOOD MONOCYTES AB The antineoplastic agent bryostatin-1 (bryo-1) possesses powerful immunomodulatory properties and can function as a biological response modifier in vivo. However, there is currently little information regarding the effects of bryo-1 on cells of the monocytic lineage. In this study, we demonstrate that bryo-1 can potently induce the production of pro-inflammatory cytokines from human peripheral blood monocytes. Stimulation of monocytes with subnanomolar concentrations of bryo-1 significantly upregulated the constitutive levels of interleukin-8 (IL-8) mRNA and induced the expression of IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), and IL-6 mRNA in a time and dose-dependent manner. Accordingly, secretion of all four proinflammatory cytokines was induced after monocyte exposure to bryo-1. Furthermore, we showed that bryo-1 selectively synergized with IL-2 in triggering monocyte activation, and this effect seemed to be dependent, at least in part, on the ability of bryo-1 to upregulate IL-2R gamma chain expression. Finally, we demonstrated that the responses of monocytes to bryo-1 could be blocked by the protein kinase C (PKC) inhibitors staurosporine and UCN-01, indicating a role for PMC in monocyte activation by bryo-1. These results show for the first time that bryo-1 is a powerful activator of human monocytes and suggest that stimulation of monokine secretion by bryo-1 may represent at least one of the mechanisms responsible for the in vivo antitumor activity of this drug. C1 LOUISIANA STATE UNIV,MED CTR,DEPT MED,NEW ORLEANS,LA 70112. NCI,FREDERICK CANC RES & DEV CTR,EXPT IMMUNOL LAB,FREDERICK,MD. SAIC FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RI Bosco, Maria Carla/J-7928-2016 OI Bosco, Maria Carla/0000-0003-1857-7193 NR 58 TC 30 Z9 30 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 MAY 1 PY 1997 VL 89 IS 9 BP 3402 EP 3411 PG 10 WC Hematology SC Hematology GA WX542 UT WOS:A1997WX54200040 PM 9129048 ER PT J AU Jiang, YZ Mavroudis, DA Dermime, S Molldrem, J Hensel, NF Barrett, AJ AF Jiang, YZ Mavroudis, DA Dermime, S Molldrem, J Hensel, NF Barrett, AJ TI Preferential usage of T cell receptor (TCR) V beta by allogeneic T cells recognizing myeloid leukemia cells: Implications for separating graft-versus-leukemia effect from graft-versus-host disease SO BONE MARROW TRANSPLANTATION LA English DT Article DE GVL; GVHD; BMT; CML; TCR; mHA ID BONE-MARROW TRANSPLANTATION; DISTINGUISH; MODEL AB New understanding of the alloresponse following bone marrow transplantation supports the possibility that the graft-versus-host disease (GVHD) response can be separated from a favorable graft-versus-leukemia (GVL) effect. We used chronic myeloid leukemia (CML) cells to generate 122 recipient-reactive T cell clones from a closely HLA-matched sibling responder. Clones were tested for their proliferative response to stimulator CML cells or PHA-transformed (non-leukemic) lymphoblasts. Of 78 clones tested, 32 recognized both leukemia cells and PHA blasts, 19 only CML and four only PHA blasts. The remainder were non-specific responders. This functional specificity corresponded to distinct patterns of T cell receptor (TCR) V beta usage: clones recognizing CML cells preferentially used V beta 5, V beta 6/7 while clones recognizing both CML and PHA blasts or only PHA blasts preferentially used V beta 3 and V beta 8. It may therefore be possible to identify in vitro-generated myeloid leukemia-restricted donor T cells by their pattern of V beta usage. TCR V beta antibodies could thus be used to select and expand leukemia-restricted donor T cells for transfusion after BMT to specifically enhance the GVL response. RP Jiang, YZ (reprint author), NHLBI,BONE MARROW TRANSPLANTAT UNIT,HEMATOL BRANCH,NIH,BLDG 10,ROOM 7C-103,BETHESDA,MD 20892, USA. RI Dermime, Said/C-6235-2009 OI Dermime, Said/0000-0002-5526-7496 NR 21 TC 25 Z9 29 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAY PY 1997 VL 19 IS 9 BP 899 EP 903 DI 10.1038/sj.bmt.1700769 PG 5 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA WX209 UT WOS:A1997WX20900006 PM 9156263 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 may play a role in the relapse of myeloid leukemias following allogeneic bone marrow transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article DE BMT; GVL; relapse; CML; AML; immune escape ID T-CELL DEPLETION; MELANOMA-CELLS; TUMOR REJECTION; LYMPHOCYTES-T; FAS ANTIGEN; I RNA; EXPRESSION; IDENTIFICATION; SUSCEPTIBILITY; COSTIMULATION AB We studied patients relapsing with myeloid leukemias following allogeneic bone marrow transplantation (BMT) for evidence of immune escape by clonal evolution of the leukemia. Relapsed cells from four out of five patients had a reduced ability to stimulate proliferation of lymphocytes from an HLA-mismatched responder, There was decreased susceptibility to lysis by CTL in three and reduced susceptibility to NK-mediated lysis in one, Relapsed leukemias had marked alterations in expression of critical surface molecules involved in immune responsiveness, Three had decreased expression of MHC class I and II, with no change or increase in CD54 (ICAM-1) or CD80 (B7.1). None of these responded to treatment with donor lymphocytes. Three patients showed no change, or increased expression of MHC with no change or decrease in ICAM-1 or B7.1. Two achieved remission-one in response to donor lymphocytes and one following withdrawal of cyclosporine. In one patient transplanted with myelodysplastic syndrome in transformation, interferon-gamma upregulated expression of MHC molecules in relapsed cells and increased their stimulatory capacity and target susceptibility to unmatched responder lymphocytes. These results suggest that immune escape through clonal evolution of the leukemia is a common occurrence in patients who relapse with myelogenous leukemias after BMT. C1 NHLBI,BMT UNIT,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. RI Dermime, Said/C-6235-2009 OI Dermime, Said/0000-0002-5526-7496 NR 30 TC 64 Z9 64 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAY PY 1997 VL 19 IS 10 BP 989 EP 999 DI 10.1038/sj.bmt.1700778 PG 11 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA WZ862 UT WOS:A1997WZ86200006 PM 9169643 ER PT J AU Rumsey, JM Horwitz, B Donohue, BC Nace, K Maisog, JM Andreason, P AF Rumsey, JM Horwitz, B Donohue, BC Nace, K Maisog, JM Andreason, P TI Phonological and orthographic components of word recognition - A PET-rCBF study SO BRAIN LA English DT Article DE PET; reading; phonological; orthographic; lexical decision making ID POSITRON EMISSION TOMOGRAPHY; HUMAN EXTRASTRIATE CORTEX; INFERIOR TEMPORAL-LOBE; HUMAN-BRAIN; READING ALOUD; FUNCTIONAL-ORGANIZATION; SCINTIGRAPHIC IMAGES; AUTOMATED-METHOD; STIMULUS RATE; ANATOMY AB Pronunciation (of irregular/inconsistent words and of pseudowords) and lexical decision-making tasks were used with O-15 PET to examine the neural correlates of phonological and orthographic processing in 14 healthy right-handed men (aged 18-40 years). Relative to a visual-fixation control task, all four experimental tasks elicited a left-lateralized stream of activation involving the lingual and fusiform gyri, perirolandic cortex, thalamus and anterior cingulate. Both pronunciation tasks activated the left superior temporal gyrus, with significantly greater activation seen there during phonological (pseudoword) than during orthographic (real word) pronunciation. The left inferior frontal cortex was activated by both decision-making tasks; more intense and widespread activation was seen there during phonological, than during orthographic, decision making, with the activation during phonological decision-making extending into the left insula. Correlations of reference voxels in the left superior temporal gyrus and left inferior frontal region with the rest of the brain were highly similar for the phonological and orthographic versions of each task type. These results are consistent with connectionist models of reading, which hypothesize that both real words and pseudowords are processed within a common neural network. C1 NIA, NEUROSCI LAB, BETHESDA, MD 20892 USA. NIA, NEUROSCI LAB, BETHESDA, MD 20892 USA. NIMH, PSYCHOL & PSYCHOPATHOL LAB, BETHESDA, MD 20892 USA. US FDA, DIV NEUROPHARMACOL DRUG PROD, ROCKVILLE, MD 20857 USA. RP Rumsey, JM (reprint author), NIMH, CHILD PSYCHIAT BRANCH, BLDG 10, ROOM 6N240, BETHESDA, MD 20892 USA. NR 81 TC 307 Z9 309 U1 2 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD MAY PY 1997 VL 120 BP 739 EP 759 DI 10.1093/brain/120.5.739 PN 5 PG 21 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XC938 UT WOS:A1997XC93800002 PM 9183247 ER PT J AU Braun, AR Varga, M Stager, S Schulz, G Selbie, S Maisog, JM Carson, RE Ludlow, CL AF Braun, AR Varga, M Stager, S Schulz, G Selbie, S Maisog, JM Carson, RE Ludlow, CL TI Altered patterns of cerebral activity during speech and language production in developmental stuttering - An H-2 O-15 positron emission tomography study SO BRAIN LA English DT Review DE dysfluency; lateralization; auditory; frontal; paralimbic ID OLD-WORLD MONKEY; ELECTRICAL-STIMULATION; BLOOD-FLOW; FRONTAL-LOBE; FUNCTIONAL-ANATOMY; CHILD STUTTERERS; CINGULATE CORTEX; SENTENCE LENGTH; NORMAL SPEAKERS; PREMOTOR AREAS AB To assess dynamic brain function in adults who had stuttered since childhood, regional cerebral blood flow (rCBF) was measured with H2O and PET during a series of speech and language tasks designed to evoke or attenuate stuttering. Speech samples were acquired simultaneously and quantitatively compared with the PET images. Both hierarchical task contrasts and correlational analyses (rCBF versus weighted measures of dysfluency) were performed. rCBF patterns in stuttering subjects differed markedly during the formulation and expression of language, failing to demonstrate left hemispheric lateralization typically observed in controls; instead regional responses were either absent, bilateral or lateralized to the right hemisphere. Significant differences were detected between groups when all subjects were fluent-during both language formulation and nonlinguistic oral motor tasks-demonstrating that cerebral function may be fundamentally different in persons who stutter; even in the absence of stuttering. Comparison of scans acquired during fluency versus dysfluency-evoking tasks suggested that during the production of stuttered speech, anterior forebrain regions-which play an a role in the regulation of motor function-are disproportionately active in stuttering subjects, while post-rolandic regions-which play a role in perception and decoding of sensory information-are relatively silent. Comparison of scans aqcuired during these conditions in control subjects, which provide information about the sensorimotor or cognitive features of the language tasks themselves, suggest a mechanism by which fluency-evoking manoeuvers might differentially affect activity in these anterior and posterior brain regions and may thus facilitate fluent speech production in individuals who stutter Both correlational and contrast analyses suggest that right and left hemispheres play distinct and opposing roles in the generation of stuttering symptoms: activation of left hemispheric regions appears to be related to the production of stuttered speech, while activation of right hemispheric regions may represent compensatory processes associated with attenuation of stuttering symptoms. C1 NIDCD,NIH,VOICE & SPEECH SECT,VOICE SPEECH & LANGUAGE BRANCH,BETHESDA,MD 20892. NIMH,NIH,LAB PHYSIOL & PSYCHOPATHOL,BETHESDA,MD 20892. NIH,CTR CLIN,PET IMAGING SECT,BETHESDA,MD 20892. RP Braun, AR (reprint author), NIDCD,NIH,LANGUAGE SECT,BLDG 10,ROOM 5N118A,BETHESDA,MD 20892, USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 120 TC 186 Z9 195 U1 9 U2 24 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0006-8950 J9 BRAIN JI Brain PD MAY PY 1997 VL 120 BP 761 EP 784 DI 10.1093/brain/120.5.761 PN 5 PG 24 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XC938 UT WOS:A1997XC93800003 PM 9183248 ER PT J AU McPherson, DR McClellan, AD O'Donovan, MJ AF McPherson, DR McClellan, AD O'Donovan, MJ TI Optical imaging of neuronal activity in tissue labeled by retrograde transport of Calcium Green Dextran SO BRAIN RESEARCH PROTOCOLS LA English DT Article DE Ca2+-sensitive fluorescent dye; optical recording; retrograde labeling; dextran-conjugated dye; cell calcium ID SPINAL-CORD; PURKINJE-CELLS; LAMPREY; INDICATORS; TRANSIENTS; DENDRITES; INVITRO; EMBRYO; DYES AB In many neurophysiological studies it is desirable to simultaneously record the activity of a large number of neurons. This is particularly true in the study of vertebrate motor systems that generate rhythmic behaviors, such as the pattern generator for locomotion in vertebrate spinal cord. Optical imaging of neurons labeled with appropriate fluorescent dyes, in which fluorescence is activity-dependent, provides a means to record the activity of many neurons at the same time, while also providing fine spatial resolution of the position and morphology of active neurons. Voltage-sensitive dyes have been explored for this purpose and have the advantage of rapid response to transmembrane voltage changes [3,7]. However, voltage-sensitive dyes bleach readily, which results in phototoxic damage and limits the time that labeled neurons can be imaged. In addition, the signal-to-noise ratio is typically small, so that averaging of responses is usually required [3,7,8]. As an alternative to voltage-sensitive dyes, calcium-sensitive dyes can exhibit large changes in fluorescence [9]. Most neurons contain voltage-sensitive Ca2+ channels, and numerous reports indicate that neuronal activity is accompanied by increased intracellular Ca2+ concentration [14,16,21,22,24,25]. In this protocol we describe a method to use retrograde transport of the dextran conjugate [6] of a calcium-sensitive dye (Calcium Green Dextran) to label selectively populations of brain and spinal interneurons in a primitive vertebrate (lamprey), for subsequent video-rate imaging of changes in intracellular fluorescence during neuronal activity. Although described with specific reference to lampreys, the technique has also been applied to embryonic chick spinal cord and larval zebrafish preparations and should be easily adaptable to other systems [4,15,16]. The most significant novel feature of the protocol is the use of retrograde axonal transport to selectively fill neurons that have known axonal trajectories. Using lampreys, we have obtained activity-sensitive labeling across longer distances and over a longer transport time (up to 14 mm and 4 days) than has been reported in other species [4,14,16]. In addition, retrograde transport allows filling of neurons more deeply within tissue than would be possible with bath application of calcium-sensitive dyes. Furthermore, the dyes are readily taken up by adult tissues, while bath application is usually limited to embryonic and neonatal vertebrate nervous tissues (although the reasons for this limitation are not clear), Attempts to load the AM (acetomethoxy) esters of calcium-sensitive dyes into lamprey spinal cord neurons by bath application have been unsuccessful (McPherson, unpublished observations, and [1]). C1 SUNY Geneseo, Dept Biol, Geneseo, NY 14454 USA. Univ Missouri, Div Biol Sci, Columbia, MO 65211 USA. NINDS, Neural Control Lab, NIH, Bethesda, MD 20892 USA. RP McPherson, DR (reprint author), SUNY Geneseo, Dept Biol, Geneseo, NY 14454 USA. NR 27 TC 12 Z9 13 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1385-299X J9 BRAIN RES PROTOC JI Brain Res. Protoc. PD MAY PY 1997 VL 1 IS 2 BP 157 EP 164 DI 10.1016/S1385-299X(96)00024-4 PG 8 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA YP318 UT WOS:000071264900010 PM 9385080 ER PT J AU Adams, DH Yannelli, JR Newman, W Lawley, T Ades, E Rosenberg, SA Shaw, S AF Adams, DH Yannelli, JR Newman, W Lawley, T Ades, E Rosenberg, SA Shaw, S TI Adhesion of tumour infiltrating lymphocytes to endothelium: A phenotypic and functional analysis SO BRITISH JOURNAL OF CANCER LA English DT Article DE tumour-infiltrating lymphocytes; endothelium; melanoma ID T-CELL ACTIVATION; LEUKOCYTE ADHESION; METASTATIC MELANOMA; EFFECTOR-CELLS; ADOPTIVE IMMUNOTHERAPY; HOMING RECEPTOR; LYMPH-NODE; L-SELECTIN; EXPRESSION; ANTIGEN AB Efficacy of cancer immunotherapy with cultured tumour-infiltrating lymphocytes (TILs) depends upon infused TILs migrating into tumour-bearing tissue, in which they mediate an anti-tumour response. For TILs to enter a tumour, they must first bind to tumour endothelium, and this process depends on TILs expressing and regulating the function of relevant cell-surface receptors. We analysed the cell-surface phenotype and endothelial binding of TILs cultured from human melanoma and compared them with peripheral blood T cells end with allostimulated T cells cultured under similar conditions. Compared with peripheral blood T cells, TILs expressed high levels of five integrins, two other adhesion molecules, including the skin homing molecule CLA, and several activation markers and showed markedly enhanced integrin-mediated adhesion to a dermal microvascular endothelial cell line in vitro. Compared with the allostimulated T cells, TILs expressed higher levels of the cutaneous lymphocyte antigen (CLA), the adhesion molecule CD31 and the activation markers CD30 and CD69, but lower levels of several other adhesion and activation molecules. These phenotypic and functional properties of TILs should have complex effects on their migration in vivo. Expression of CLA, the skin homing receptor, may increase migration to melanoma (a skin cancer), whereas integrin activation may cause non-specific binding of TILs to other endothelium. Manipulation of the culture conditions in which TILs are expanded might result in a phenotype that is more conducive to selective tumour homing in vivo. C1 NCI,EXPT IMMUNOL BRANCH,BETHESDA,MD. NCI,SURG BRANCH,BETHESDA,MD. LEUKOSITE,BOSTON,MA 02115. EMORY UNIV,SCH MED,DEPT DERMATOL,ATLANTA,GA 30341. CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,SCI RESOURCES PROGRAM,BIOL PROD BRANCH,ATLANTA,GA 30333. RP Adams, DH (reprint author), UNIV BIRMINGHAM,DEPT MED,LIVER RES LABS,BIRMINGHAM B15 2TH,W MIDLANDS,ENGLAND. RI Adams, David/C-9092-2009 NR 71 TC 24 Z9 24 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAY PY 1997 VL 75 IS 10 BP 1421 EP 1431 DI 10.1038/bjc.1997.245 PG 11 WC Oncology SC Oncology GA WZ284 UT WOS:A1997WZ28400004 PM 9166933 ER PT J AU Sato, T Selleri, C Anderson, S Young, NS Maciejewski, JP AF Sato, T Selleri, C Anderson, S Young, NS Maciejewski, JP TI Expression and modulation of cellular receptors for interferon-gamma, tumour necrosis factor, and Fas on human bone marrow CD34(+) cells SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE CD34(+) cells; bone marrow; IFN-gamma R; TNFR; Fas-R ID HEMATOPOIETIC PROGENITOR CELLS; FACTOR-INDUCED PROLIFERATION; COLONY-STIMULATING FACTOR; SEVERE APLASTIC-ANEMIA; ALPHA TNF-ALPHA; IN-VITRO; MYELODYSPLASTIC SYNDROMES; MOLECULAR-CLONING; SURFACE ANTIGEN; GENE-EXPRESSION AB Interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and Fas-ligand can mediate potent inhibitory signals in haemopoietic cells. Clinical and laboratory studies have suggested the involvement of these cytokines in the regulation of normal haemopoiesis and in the pathophysiology of bone marrow (BM) failure syndromes. As the effects of cytokines may also be regulated at the cellular receptor level, we studied the expression and modulation of TNF receptor (TNFR), IFN-gamma R and Fas-R on haemopoietic progenitor cells. In freshly isolated BM, using now cytometry, TNFR1 (p55), TNFR2 (p75), IFN-gamma R, and Fas-R were detected on 5-12% of mononuclear cells. Two-colour staining showed comparable receptor expression on a CD34(+) population, which includes haemopoietic progenitor and stem cells. Using reverse transcriptase-PCR (RT-PCR) transcription of mRNA coding for these receptors was demonstrated in fresh, highly purified CD34(+) cells. These findings indicate that the effects of these factors on progenitor cells may be directly mediated. In cultured BM cells, expression of TNFR1 was not influenced by IFN-gamma, TNF-alpha or apoptosis-inducing anti-Fas monoclonal antibody (mAb). IFN-gamma decreased CD34(+) cell TNFR2 expression. CD34(+) cell Fas-R expression was increased by IFN-gamma and TNF-alpha. IFN-gamma R expression was enhanced by anti-Fas mAb and to lesser degree with TNF-alpha. Similar results were obtained with RT-PCR analysis in cultured CD34(+) cells. Potentiation of anti-Pas mAb-mediated inhibition of haemopoietic colony formation by IFN-gamma and TNF-alpha was observed. Similarly, anti-Fas mAb enhanced the inhibitory effects of IFN-gamma. These results suggest that, in addition to interacting at the level of intracellular signalling pathways, IFN-gamma, TNF-alpha or Fas-ligand may potentiate or antagonize their effects through modulation of cytokine receptor expression. C1 NHLBI,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. NR 54 TC 58 Z9 58 U1 1 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAY PY 1997 VL 97 IS 2 BP 356 EP 365 DI 10.1046/j.1365-2141.1997.562704.x PG 10 WC Hematology SC Hematology GA WZ562 UT WOS:A1997WZ56200020 PM 9163602 ER PT J AU Brown, KE Wong, S Young, NS AF Brown, KE Wong, S Young, NS TI Prevalence of GBV-C/HGV, a novel 'hepatitis' virus, in patients with aplastic anaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE Flaviviridae; non-A non-B hepatitis; epidemiology; prevalence; aplastic anaemia ID NON-A; NON-B; FULMINANT-HEPATITIS; NON-C; ANEMIA AB GBV-C or hepatitis G virus (GBV-C/HGV) is a novel RNA virus with similarities to members of the Flaviviridae family, especially hepatitis C. Viral RNA is detected in about 1.5% of American blood donors, with higher prevalence in multiply transfused patients and in individuals with hepatitis or liver disease. Some cases of aplastic anaemia follow apparent non-A, non-B, non-C viral hepatitis, and GBV-C viraemia has been described in three case reports of hepatitis-associated aplastic anaemia. We tested clinical samples from patients with aplastic anaemia with or without recent hepatitis for the presence of GBV-C/HGV. Virus was detected in a total of 15/57 (26.3%) of patients with aplastic anaemia and 12/52 (23.1%)of multiply transfused control patients. Sequencing of the 188 base pair NS3 helicase PCR product in the serum of five individuals indicated the same high degree of sequence variation as has been seen among other isolates of the virus. GBV-C/HGV does not appear to be implicated in the aetiology of aplastic anaemia. C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 30 TC 30 Z9 30 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAY PY 1997 VL 97 IS 2 BP 492 EP 496 DI 10.1046/j.1365-2141.1997.822722.x PG 5 WC Hematology SC Hematology GA WZ562 UT WOS:A1997WZ56200039 PM 9163622 ER PT J AU Smart, CR Byrne, C Smith, RA Garfinkel, L Letton, AH Dodd, GD Beahrs, OH AF Smart, CR Byrne, C Smith, RA Garfinkel, L Letton, AH Dodd, GD Beahrs, OH TI Twenty-year follow-up of the breast cancers diagnosed during the Breast Cancer Detection Demonstration Project SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article ID WOMEN; INSIGHTS; AGE AB This study reports on the 20-year follow-up of the women diagnosed with breast cancer in the Breast Cancer Detection Demonstration Project (BCDDP) between 1973 and 1980. This project provided 5 years of screening with physical examination and two-view mammography for 280,000 volunteer women across the United States. Based on a 96% follow-up from 1993 to 1995 of the 4,051 women with breast cancer available for analysis, 2,658 (66%) were alive and 1,393 (34%) were dead A high proportion of the cancers were detected by mammography alone, and 28.6% of all the cancers were smaller than 1.0 cm. Survival rates were calculated by life table method with deaths from breast cancer as the outcome. The adjusted survival rate for the entire group was 80.5%, and the observed survival rate was 61.7%. Adjusted and observed survival rates were 97.2% and 78.5%, respectively, for women with noninvasive cancers and 78.2% and 59.3%, respectively, for those with invasive cancers. Lymph node status and the size of the cancer at diagnosis were prognostic indicators of survival in the BCDDP. Women with invasive cancers and negative lymph nodes had an 85.5% breast cancer survival rate and a 65.6% observed survival rate. Adjusted survival rates for women with invasive breast cancers were 90.2% for cancers smaller than 1 cm, 80.5% for cancers 1.0 to 1.9 cm, 70.5% for cancers 2.0 to 4.9 cm, and 60.6% for cancers larger than 5 cm. Women 40 to 49 years of age demonstrated a greater survival with noninvasive or invasive cancers smaller than 5.0 cm compared with women 50 to 59 and 60 to 69 years of age at diagnosis. These results from the BCDDP are discussed in the context of the recent decline in breast cancer incidence and mortality in the United States. C1 HARVARD UNIV,SCH MED,CHANNING LAB,BOSTON,MA 02115. AMER CANC SOC,CANC DETECT & TREATMENT,ATLANTA,GA 30329. AMER CANC SOC,CANC PREVENT,EPIDEMIOL & STAT,NEW YORK,NY. UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX. MAYO CLIN & MAYO FDN,MAYO MED SCH,ROCHESTER,MN 55905. NCI,EARLY DETECT BRANCH,BETHESDA,MD 20892. GEORGIA BAPTIST MED CTR BCDDP,ATLANTA,GA. RI Byrne, Celia/K-2964-2015 OI Byrne, Celia/0000-0001-8289-4252 NR 21 TC 83 Z9 86 U1 0 U2 0 PU AMER CANCER SOC PI NEW YORK PA C/O JB LIPPINCOTT CO 1180 AVE OF THE AMERICAS 6TH FLOOR, NEW YORK, NY 10036 SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD MAY-JUN PY 1997 VL 47 IS 3 BP 134 EP 149 DI 10.3322/canjclin.47.3.134 PG 16 WC Oncology SC Oncology GA WY922 UT WOS:A1997WY92200002 PM 9152171 ER PT J AU Bassett, L Winchester, DP Caplan, RB Dershaw, DD Dowlatshahi, K Evans, WP Fajardo, LL Fitzgibbons, PL Henson, DE Hutter, RVP Morrow, M Paquelet, JR Singletary, SE Curry, J WilcoxBuchalla, P Zinninger, M AF Bassett, L Winchester, DP Caplan, RB Dershaw, DD Dowlatshahi, K Evans, WP Fajardo, LL Fitzgibbons, PL Henson, DE Hutter, RVP Morrow, M Paquelet, JR Singletary, SE Curry, J WilcoxBuchalla, P Zinninger, M TI Stereotactic core-needle biopsy of the breast: A report of the joint task force of the American College of Radiology, American College of Surgeons, and College of American Pathologists SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article ID PROBABLY BENIGN LESIONS; MAMMOGRAPHIC FOLLOW-UP; NONPALPABLE BREAST; ASPIRATION CYTOLOGY; SCREENING MAMMOGRAPHY; COST-EFFECTIVENESS; PALPABLE LESIONS; APPROPRIATE ROLE; SURGICAL BIOPSY; CARCINOMA AB A national task force consisting of members from the American College of Radiology, the American College of Surgeons, and the College of American Pathologists examined the issuses surrounding stereotactic core-needle biopsy for occult breast lesions. Their report includes indications and contraindications, informed consent, specimen handling, and management of indeterminate, atypical, or discordant lesions. C1 NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. AMER COLL SURG,CANC DEPT,CHICAGO,IL. AMER SOC BREAST SURG,PORTSMOUTH,VA. MEM SLOAN KETTERING CANC CTR,DEPT RADIOL,BREAST IMAGING SECT,NEW YORK,NY 10021. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. BAYLOR UNIV,MED CTR,SUSAN G KOMEN BREAST CTR,DALLAS,TX. UNIV VIRGINIA,DEPT RADIOL,CHARLOTTESVILLE,VA 22908. ST JUDE MED CTR,DEPT PATHOL,FULLERTON,CA. NCI,EARLY DETECT BRANCH,BETHESDA,MD 20892. ST BARNABAS HOSP,DEPT PATHOL,LIVINGSTON,NJ. NORTHWESTERN UNIV,SCH MED,LYNN SAGE COMPREHENS BREAST PROGRAM,CHICAGO,IL. COLUMBUS RADIOL CORP,GRANT MED CTR,COLUMBUS,OH. UNIV TEXAS,MD ANDERSON CANC CTR,BREAST SURG SECT,HOUSTON,TX. AMER COLL RADIOL,ACCREDITATION PROGRAMS,RESTON,VA. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. OI Fitzgibbons, Patrick/0000-0002-2998-6913 NR 80 TC 96 Z9 97 U1 0 U2 1 PU AMER CANCER SOC PI NEW YORK PA C/O JB LIPPINCOTT CO 1180 AVE OF THE AMERICAS 6TH FLOOR, NEW YORK, NY 10036 SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD MAY-JUN PY 1997 VL 47 IS 3 BP 171 EP & DI 10.3322/canjclin.47.3.171 PG 21 WC Oncology SC Oncology GA WY922 UT WOS:A1997WY92200006 PM 9152175 ER PT J AU McBain, CJ Maccaferri, G AF McBain, CJ Maccaferri, G TI Synaptic plasticity in hippocampal interneurons? A commentary SO CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT Symposium of the Centre-de-Recherche-en-Sciences-Neurologiques-of-the-Universite-de-Montr eal on GABA Mechanisms in the Cerebral Cortex CY MAY 09-10, 1996 CL MONTREAL, CANADA SP Univ Montreal, Ctr Rech Sci Neurol DE hippocampus; interneurons; long-term potentiation; long-term depression; plasticity; GABAergic; CA1 ID LONG-TERM POTENTIATION; PROTEIN-KINASE ACTIVITY; RAT HIPPOCAMPUS; AREA CA1; DEPRESSION; TRANSMISSION; INHIBITION; ACTIVATION; MECHANISMS; NEURONS AB The hypothesis that excitatory synapses onto hippocampal inhibitory interneurons undergo farms of synaptic plasticity similar to that observed in principal pyramidal neurons has received much attention in the last few years. No general consensus exists, however, concerning the presence (or absence) of long-term potentiation and depression in nonpyramidal neurons. A large source of this disagreement stems from the experimental paridigms chosen to elicit synaptic plasticity in the various studies, since most of the induction protocols used did not permit the separation of plasticity occurring on principal cells from possible direct plasticity on the interneurons themselves. In this commentary we discuss some of the issues surrounding these data and also address some of the technical considerations one must address before the presence or absence of long-term potentiation in interneurons can be answered unequivocally. RP McBain, CJ (reprint author), NICHHD,LAB CELLULAR & MOL NEUROPHYSIOL,NIH,ROOM 5A72,BLDG 49,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 47 TC 17 Z9 17 U1 0 U2 1 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0008-4212 J9 CAN J PHYSIOL PHARM JI Can. J. Physiol. Pharmacol. PD MAY PY 1997 VL 75 IS 5 BP 488 EP 494 DI 10.1139/cjpp-75-5-488 PG 7 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA XM246 UT WOS:A1997XM24600016 PM 9250382 ER PT J AU Ji, BT Chow, WH McLaughlin, JK Fraumeni, JF AF Ji, BT Chow, WH McLaughlin, JK Fraumeni, JF TI The influence of cigarette smoking, alcohol, and green tea consumption on the risk of carcinoma of the cardia and distal stomach in Shanghai, China - Reply SO CANCER LA English DT Letter ID GASTRIC-CANCER; JAPAN; DIET RP Ji, BT (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,ROCKVILLE,MD, USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD MAY 1 PY 1997 VL 79 IS 9 BP 1841 EP 1841 DI 10.1002/(SICI)1097-0142(19970501)79:9<1841::AID-CNCR30>3.0.CO;2-W PG 1 WC Oncology SC Oncology GA WU761 UT WOS:A1997WU76100030 ER PT J AU Zachrau, RE Hankey, BF Feuer, EJ AF Zachrau, RE Hankey, BF Feuer, EJ TI Prognostic significance of in situ carcinoma associated with invasive breast carcinoma - A natural experiment in cancer immunology? Reply SO CANCER LA English DT Letter C1 NCI,DIV CANC PREVENT & CONTROL,SURVEILLANCE PROGRAM,CANC STAT BRANCH,BETHESDA,MD 20892. NCI,DIV CANC PREVENT & CONTROL,SURVEILLANCE PROGRAM,APPL RES BRANCH,BETHESDA,MD 20892. RP Zachrau, RE (reprint author), NEW YORK MED COLL,INST BREAST DIS,VALHALLA,NY 10595, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD MAY 1 PY 1997 VL 79 IS 9 BP 1847 EP 1848 DI 10.1002/(SICI)1097-0142(19970501)79:9<1847::AID-CNCR36>3.0.CO;2-W PG 2 WC Oncology SC Oncology GA WU761 UT WOS:A1997WU76100036 ER PT J AU Cantor, KP AF Cantor, KP TI Drinking water and cancer SO CANCER CAUSES & CONTROL LA English DT Article DE arsenic; asbestos; cancer; disinfection byproducts; drinking water; fluoride; nitrate ID LOW-RISK AREAS; RADIUM GROUNDWATER CONTAMINATION; NITRATE FERTILIZER WORKERS; DISINFECTION BY-PRODUCTS; UNITED-STATES CITIES; DISEASE ENDEMIC AREA; ASBESTOS-CEMENT PIPE; N-NITROSAMINO ACIDS; FRANCISCO BAY AREA; WELL-WATER AB Epidemiologic evidence on the relation between contaminants in drinking water and cancer is reviewed. The reviewed studies cover exposure to: disinfection byproducts; nitrate; arsenic and other metals; volatiles and contaminants from hazardous waste sites; asbestiform fibers; radionuclides; and fluoride. Most investigations are ecologic, with some confirmation of elevated risk from individual-based studies. In the case of waterborne arsenic, and possibly chlorination byproducts, there is a consistent but small body of epidemiologic evidence of an association with one or more types of cancer. Nitrate in groundwater has increased greatly over the years, and the demonstration of endogenous nitrosation among highly exposed subjects raises concern of elevated cancer risk. However, the epidemiologic data are not yet sufficient to draw a conclusion. There is a diversity of studies among populations exposed to water contaminated with pesticides, volatile organics, or mixtures from hazardous waste sites. Studies of asbestiform fibers and radionuclides in water are not conclusive, but there are suggested elevations of several cancer sites in highly exposed populations. There is no suggestion that fluoride in drinking water is linked with elevated risk of cancer. As topics for epidemiologic evaluation, drinking water contaminants pose methodologic problems common to studies designed to detect relatively small elevations in risk, with the added challenge of assessing exposures for many years in the past. Nevertheless, epidemiologic assessment is valuable and clearly warranted, given the potential public health impact of small risk elevations among very large exposed populations, and the limitations of toxicologic experiments in assessing carcinogenic risk of complex mixtures or of compounds for which appropriate animal models are not available. RP Cantor, KP (reprint author), NCI, OCCUPAT EPIDEMIOL BRANCH, DIV CANC EPIDEMIOL & GENET, 418 EXECUT PLAZA N, BETHESDA, MD 20892 USA. NR 225 TC 217 Z9 225 U1 3 U2 66 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 1997 VL 8 IS 3 BP 292 EP 308 DI 10.1023/A:1018444902486 PG 17 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA XG202 UT WOS:A1997XG20200004 PM 9498894 ER PT J AU Boice, JD Lubin, JH AF Boice, JD Lubin, JH TI Occupational and environmental radiation and cancer SO CANCER CAUSES & CONTROL LA English DT Article DE cancer; environment; ionizing radiation; leukemia; occupation; radon ID RESIDENTIAL RADON EXPOSURE; SELLAFIELD NUCLEAR INSTALLATION; HIGH BACKGROUND-RADIATION; NEVADA TEST SITE; LUNG-CANCER; CHILDHOOD LEUKEMIA; URANIUM MINERS; UNITED-STATES; IONIZING-RADIATION; THYROID-CANCER AB Epidemiologic evidence on the relation between occupational and environmental radiation and cancer is reviewed, Studies of pioneering radiation workers, underground miners? and radium dial painters revealed excess cancer deaths and contributed to the setting of radiation protection standards and to theories of carcinogenesis, Occupational exposures today are generally much lower than in the past, thus any associated increases in cancer will be difficult to detect. Pooling investigations of these more recently exposed workers, however, has the potential to validate current estimates of risk used in radiation protection. New information on the effects of chronic radiation exposure also map come from studies in the former Soviet Union of Chernobyl clean-up workers and of workers at the Mayak nuclear facilities. Studies of environmental radiation exposures, other than radon, are largely inconclusive, due mainly to the difficulties in detecting the low risks associated with low dose exposures. Thyroid cancer, however, has been linked to environmental radiation from the Chernobyl accident and from nuclear weapons tests, Low-level radiation released during normal operations at nuclear plants has not been found to increase cancer rates in surrounding populations, Radon, a human carcinogen, is the most ubiquitous exposure to human populations; remediating high residential-radon levels is recommended, recognizing that the exposure can never be removed completely because it occurs naturally. C1 US NATL CANC INST, DIV CANC EPIDEMIOL & GENET, EPIDEMIOL & BIOSTAT PROGRAM, BETHESDA, MD USA. NR 156 TC 37 Z9 37 U1 2 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 1997 VL 8 IS 3 BP 309 EP 322 DI 10.1023/A:1018496919324 PG 14 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA XG202 UT WOS:A1997XG20200005 PM 9498895 ER PT J AU Hayes, RB AF Hayes, RB TI The carcinogenicity of metals in humans SO CANCER CAUSES & CONTROL LA English DT Review DE arsenic; beryllium; cadmium; cancer; chromium; lead; metals; nickel ID LUNG-CANCER MORTALITY; COPPER-SMELTER WORKERS; OCCUPATIONAL ARSENIC EXPOSURE; CHROMATE-PRODUCING INDUSTRY; RESPIRATORY CANCER; RETROSPECTIVE-COHORT; INDUCED GENOTOXICITY; PIGMENT WORKERS; STAINLESS-STEEL; MAMMALIAN-CELLS AB Epidemiologic evidence on the relation between exposure to metals and cancer is reviewed. Human exposure to metals is common, with wide use in industry and long-term environmental persistence. Historically, the heaviest metal exposures occurred in the workplace or in environmental settings in close proximity to industrial sources. Among the general population, exposure to a number of metals is widespread but generally at substantially lower levels than have been found in industry. The carcinogenicity of arsenic, chromium, and nickel has been established. Occupational and environmental arsenic exposure is linked to increased lung cancer risk in humans, although experimental studies remain inconclusive. Experimental studies clearly demonstrate the malignant potential of hexavalent((VI)) chromium compounds, with solubility being an important determining factor. Epidemiologic studies of workers in chromium chemical production and use link exposure to lung and nasal cancer. Experimental and epidemiologic data show that sparingly-soluble nickel compounds and possibly also the soluble compounds are carcinogens linked to lung and nasal cancer in humans. Some experimental and epidemiologic studies suggest that lead may be a human carcinogen, but the evidence is inconclusive. Although epidemiologic data are less extensive for beryllium and cadmium, the findings in humans of excess cancer risk are supported by the clear demonstration of carcinogenicity in experimental studies. Other metals, including antimony and cobalt, may be human carcinogens, but the experimental and epidemiologic data are limited. RP Hayes, RB (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,EPN 418,BETHESDA,MD 20892, USA. NR 165 TC 236 Z9 247 U1 3 U2 48 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 1997 VL 8 IS 3 BP 371 EP 385 DI 10.1023/A:1018457305212 PG 15 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA XG202 UT WOS:A1997XG20200010 PM 9498900 ER PT J AU Dich, J Zahm, SH Hanberg, A Adami, HO AF Dich, J Zahm, SH Hanberg, A Adami, HO TI Pesticides and cancer SO CANCER CAUSES & CONTROL LA English DT Review DE malignant lymphoma; occupational exposure; soft tissue sarcoma ID NON-HODGKINS-LYMPHOMA; SOFT-TISSUE SARCOMA; OCCUPATIONAL RISK-FACTORS; NESTED CASE-CONTROL; MULTIPLE-MYELOMA; PHENOXY HERBICIDES; TESTICULAR CANCER; BREAST-CANCER; UNITED-STATES; NEW-ZEALAND AB Epidemiologic evidence on the relationship between chemical pesticides and cancer is reviewed, In animal studies, many pesticides are carcinogenic, (e.g., organochlorines, creosote, and sulfallate) while others (notably, the organochlorines DDT, chlordane, and lindane) are tumor promoters, Some contaminants in commercial pesticide formulations also may pose a carcinogenic risk, In humans, arsenic compounds and insecticides used occupationally have been classified as carcinogens by the International Agency for Research on Cancer, Human data, however, are limited by the small number of studies that evaluate individual pesticides. Epidemiologic studies, although sometimes contradictory, have linked phenoxy acid herbicides or contaminants in them with soft tissue sarcoma (STS) and malignant lymphoma; organochlorine insecticides are linked with STS, non-Hodgkin's lymphoma (NHL), leukemia, and, less consistently, with cancers of the lung and breast; organophosphorous compounds are linked with NHL and leukemia; and triazine herbicides with ovarian cancer. Few, if any, of these associations can be considered established and causal, Hence, further epidemiologic studies are needed with detailed exposure assessment for individual pesticides, taking into consideration work practices, use of protective equipment, and other measures to reduce risk. C1 KAROLINSKA UNIV HOSP,RADIUM HEMMET,STOCKHOLM,SWEDEN. US NATL CANC INST,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD. KAROLINSKA INST,INST ENVIRONM MED,S-17176 STOCKHOLM,SWEDEN. UNIV UPPSALA HOSP,DEPT EPIDEMIOL,UPPSALA,SWEDEN. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,CTR CANC PREVENT,BOSTON,MA 02115. RP Dich, J (reprint author), KAROLINSKA INST,INST ONCOL PATHOL,DEPT CANC EPIDEMIOL,S-17176 STOCKHOLM,SWEDEN. RI Zahm, Shelia/B-5025-2015; OI Hanberg, Annika/0000-0001-7255-9856 NR 174 TC 219 Z9 225 U1 14 U2 49 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 1997 VL 8 IS 3 BP 420 EP 443 DI 10.1023/A:1018413522959 PG 24 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA XG202 UT WOS:A1997XG20200013 PM 9498903 ER PT J AU Blair, A Kazerouni, N AF Blair, A Kazerouni, N TI Reactive chemicals and cancer SO CANCER CAUSES & CONTROL LA English DT Review DE cancer; reactive chemicals ID ETHYLENE-OXIDE WORKERS; VINYL-CHLORIDE MONOMER; PARA-NASAL SINUSES; FORMALDEHYDE EXPOSURE; RESPIRATORY CANCER; SULFURIC-ACID; LUNG-CANCER; EPIDEMIOLOGIC EVIDENCE; OCCUPATIONAL EXPOSURE; CHLOROMETHYL-ETHERS AB Epidemiologic evidence on the relation between reactive chemicals and cancer is reviewed. These highly reactive chemicals (acrylonitrile; bis[chloromethyl]ether and chloromethyl methyl ether; 1,3-butadiene, ethylene oxide; formaldehyde; mustard gas; sulfuric acid; and vinyl chloride) vary in use and exposure. All are animal carcinogens that also have received considerable epidemiologic attention. Acrylonitrile is a chemical of current economic importance. The epidemiologic evidence is quite weak, but the available studies were very small. Epidemiologic studies clearly demonstrate that bis (chloromethyl) ether and chloromethyl methyl ether cause lung cancer. Continued follow-up of exposed workers is encouraged to provide information on risks for other cancers. Results from epidemiologic studies of butadiene-exposed workers are somewhat inconsistent, but the largest study with the best exposure assessment found the largest relative risk for leukemia. The failure of several larger studies to replicate the early Swedish findings of a very strong association between leukemia and ethylene oxide has not been adequately explained. Epidemiologic studies of formaldehyde provide limited evidence for an association with cancer of the nasopharynx and possibly with nasal cancer. These very rare tumors, however, are difficult to study epidemiologically. Mustard gas is a well-established lung carcinogen, but a recent follow-up of the English cohort suggests that other sites also may be affected. Sulfuric acid appears to cause laryngeal cancer. A suggested relationship with lung cancer in a few studies is of concern because of the widespread opportunity for exposure from ambient air pollution. Vinyl chloride causes angiosarcoma of the liver, but a large, multi-country study provided no clear evidence that other sites are affected. RP Blair, A (reprint author), NCI,OCCUPAT STUDIES SECT,EXECUT PLAZA N,ROOM 418,ROCKVILLE,MD 20892, USA. NR 129 TC 57 Z9 59 U1 1 U2 7 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 1997 VL 8 IS 3 BP 473 EP 490 DI 10.1023/A:1018417623867 PG 18 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA XG202 UT WOS:A1997XG20200015 PM 9498905 ER PT J AU An, WG Schnur, RC Neckers, L Blagosklonny, MV AF An, WG Schnur, RC Neckers, L Blagosklonny, MV TI Depletion of p185(erbB2), Raf-1 and mutant p53 proteins by geldanamycin derivatives correlates with antiproliferative activity SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE geldanamycin; p185(erbB2); mutant p53; Raf-1; cancer cells ID CANCER CELL-LINES; GENE-PRODUCT P185; BENZOQUINOID ANSAMYCINS; FUNCTION MUTATIONS; IN-VIVO; INHIBITION; RESISTANCE; RECEPTOR; KINASE; GAIN AB Purpose: Recently, it has been shown that geldanamycin (GA), a benzoquinone ansamycin, is able to deplete mutant p53, p185(erbB2) and Raf-1 proteins in cancer cells. However, the relationship between these activities of GA and its antiproliferative activity is not clear. Here we investigated the effects of 28 GA derivatives in SKBr3, a human breast cancer cell line. Methods: We performed Western blot analysis of Raf-1, p185(erbB2) and mutant p53 proteins following drug treatment and correlated these findings with the cytotoxicity of the various GA derivatives. Results: We found that downregulation of Raf-1, p185(erbB2) and mutant p53 proteins was correlated. Thus, a drug that was active against one oncoprotein was equally active against the two others. Inactive derivatives were identified by their inability to downregulate these oncoproteins, even at a high dose (2 mu M). These inactive drugs also had no or minimal antiproliferative activity (IC50 > 3 mu M). All other analogs (at a concentration of 2 mu M) downregulated p53, p185(erbB2), and Raf-1, and also displayed cytotoxicity (IC50 in the range 6-600 nM). This category of drugs was further divided into more- and less-active agents by testing at lower doses (40 nM). The drugs that remained active against their molecular targets had an IC50 for antiproliferative activity of less than 40 nM. Maximal effects on mutant p53, p185(erbB2) and Raf-1 were observed at doses that were 4-5 times greater than the cytotoxic IC50. Conclusions: These findings suggest that GA and its derivatives are cytostatic/cytotoxic at concentrations that also downregulate Raf-1, p185(erbB2) and mutant p53, and raise the possibility that depletion of these proteins and the antiproliferative activities of GA have a common mechanism. C1 NCI,CLIN PHARMACOL BRANCH,NIH,BETHESDA,MD 20892. PFIZER INC,PFIZER CENT RES,GROTON,CT 06340. NR 27 TC 103 Z9 104 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 MAY PY 1997 VL 40 IS 1 BP 60 EP 64 DI 10.1007/s002800050626 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA WW321 UT WOS:A1997WW32100010 PM 9137531 ER PT J AU Marshall, LM Hunter, DJ Connolly, JL Schnitt, SJ Byrne, C London, SJ Colditz, GA AF Marshall, LM Hunter, DJ Connolly, JL Schnitt, SJ Byrne, C London, SJ Colditz, GA TI Risk of breast cancer associated with atypical hyperplasia of lobular and ductal types SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID DISEASE; WOMEN AB Epidemiological studies Ising the histological classification of Page for benign breast disease consistently demonstrate a positive association between atypical hyperplasia and the subsequent development of breast cancer, However, atypical hyperplasia is of either lobular or ductal types, and breast cancer risk in relation to type of atypical hyperplasia has not been studied extensively, Thus, we investigated prospectively the risk of breast cancer associated with histological subtypes of benign proliferative breast disease, including the types of atypical. hyperplasia, among participants in the Nurses' Health Study who had biopsy-confirmed benign breast disease, Women who subsequently developed breast cancer were matched by year of birth and year of biopsy to participants who were free from breast cancer, Benign biopsy slides were classified according to the criteria of Page. Odds ratios (ORs) of breast cancer and 95% confidence intervals (CIs), adjusted for the matching variables and other breast cancer risk factors, were computed using unconditional logistic regression,vith benign nonproliferative breast disease as the referent group, Atypical ductal hyperplasia (OR = 2.4; 95% CI, 1.3-4.5) or atypical lobular hyperplasia (OR = 5.3; 95% CI, 2.7-10.4) in a prior biopsy were associated with increased breast cancer risk, Atypical lobular hyperplasia was more strongly associated,vith the risk of premenopausal breast cancer (OR = 9.6; 95% CI, 3.3-27.8) than with the risk of postmenopausal breast cancer (OR = 3.7; 95% CI, 1.3-10.2), The association of atypical ductal hyperplasia and breast cancer risk varied little by menopausal status. The magnitude of breast cancer risk seems to vary according to the type of atypical hyperplasia present at biopsy. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,CHANNING LAB,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. HARVARD UNIV,CTR CANC PREVENT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. BETH ISRAEL HOSP,BOSTON,MA 02115. NIEHS,RES TRIANGLE PK,NC 27709. RI Colditz, Graham/A-3963-2009; Byrne, Celia/K-2964-2015; OI Colditz, Graham/0000-0002-7307-0291; Byrne, Celia/0000-0001-8289-4252; London, Stephanie/0000-0003-4911-5290 FU NCI NIH HHS [CA46475]; NIEHS NIH HHS [ES07069] NR 16 TC 151 Z9 153 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 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 1997 VL 6 IS 5 BP 297 EP 301 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA WZ603 UT WOS:A1997WZ60300001 PM 9149887 ER PT J AU Schreiber, G Fong, KM Peterson, B Johnson, BE OBriant, KC Bepler, G AF Schreiber, G Fong, KM Peterson, B Johnson, BE OBriant, KC Bepler, G TI Smoking, gender, and survival association with allele loss for the LOH11B lung cancer region on chromosome 11 SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID TUMOR PROGRESSION; RAS ONCOGENE; SHORT ARM; CELL; GENES; DNA; HYPOMETHYLATION; ADENOCARCINOMA; HETEROZYGOSITY; CHEMOTHERAPY AB We have reported frequent allele loss for the marker HRAS on chromosome lip in human lung cancer and defined the smallest common region of deletion (designated LOH11B) to approximately 500 kb, Here, we investigated the association of allele loss for LOR11B with epidemiological, pathological, and clinical parameters, Analysis of allele loss was performed using Southern blotting on a cohort of 200 patients with lung cancer, and data were interpreted with the use of a phosphorimager, Results were statistically compared with retrospectively collected variables, LOH11B allele loss was significantly associated,vith cigarette consumption (P = 0.009), gender (P = 0.02), and survival (P = 0.04), None of the nonsmokers had allele loss as compared with 28% of the patients with low and 43% with high cigarette consumption, Allele loss was more frequent in men (43%) than in women (11%), The median survival of patients without allele loss was 42 months compared with 25 months for patients with allele loss, These results suggest that the LOH11B region contains a gene responsible for a more malignant phenotype independent of the metastatic potential of lung cancer, They also suggest that alterations in this gene are associated with cigarette consumption and are more frequent in men than in women. C1 DUKE UNIV, MED CTR, DEPT MED, DURHAM, NC 27710 USA. DUKE UNIV, MED CTR, DUKE COMPREHENS CANC CTR BIOSTAT, DURHAM, NC 27710 USA. UNIV QUEENSLAND, SCH MED, DEPT PATHOL, HERSTON, QLD 4006, AUSTRALIA. PRINCE CHARLES HOSP, DEPT THORAC MED, CHERMSIDE, QLD 4032, AUSTRALIA. NATL NAVAL MED CTR, NCI, NAVY MED ONCOL BRANCH, BETHESDA, MD 20889 USA. RI Fong, Kwun/G-6369-2010 NR 47 TC 13 Z9 13 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 MAY PY 1997 VL 6 IS 5 BP 315 EP 319 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA WZ603 UT WOS:A1997WZ60300004 PM 9149890 ER PT J AU Eng, C Schneider, K Fraumeni, JF Li, FP AF Eng, C Schneider, K Fraumeni, JF Li, FP TI Third international workshop on collaborative interdisciplinary studies of p53 and other predisposing genes in Li-Fraumeni syndrome SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID SPONTANEOUS TUMORIGENESIS; MUTATIONS; MICE; TUMORS C1 DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NCI,DIV CANC EPIDEMIOL & GENET,NIH,BETHESDA,MD 20893. OI Eng, Charis/0000-0002-3693-5145 NR 17 TC 25 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 MAY PY 1997 VL 6 IS 5 BP 379 EP 383 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA WZ603 UT WOS:A1997WZ60300013 PM 9149899 ER PT J AU Yang, JC AF Yang, JC TI Of snails and holy grails ... SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Editorial Material ID INTERLEUKIN-2 RP Yang, JC (reprint author), NCI,SURG BRANCH,NIH,BLDG 10,ROOM 2B42,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD MAY-JUN PY 1997 VL 3 IS 3 BP 142 EP 143 PG 2 WC Oncology SC Oncology GA XC487 UT WOS:A1997XC48700004 PM 9161778 ER PT J AU Ma, GY Bartlett, DL Reed, E Figg, WD Lush, RM Lee, KB Libutti, SK Alexander, HR AF Ma, GY Bartlett, DL Reed, E Figg, WD Lush, RM Lee, KB Libutti, SK Alexander, HR TI Continuous hyperthermic peritoneal perfusion with cisplatin for the treatment of peritoneal mesothelioma SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Article DE hyperthermia; peritoneal perfusion; cisplatin; mesothelioma ID MITOMYCIN-C; MALIGNANT MESOTHELIOMA; GASTRIC-CANCER; CHEMOTHERAPY; RECURRENCE AB PURPOSE Peritoneal mesothelioma remains a difficult therapeutic challenge. Aggressive debulking combined with continuous hyperthermic peritoneal perfusion (CHPP) using cisplatin (CDDP) is a novel strategy for the treatment of peritoneal mesothelioma, allowing high regional delivery of chemotherapeutics and hyperthermia while minimizing systemic toxicity. PATIENTS AND METHODS From June 1933 to May 1996, 10 patients with peritoneal mesothelioma (six men, four women; mean age 40 years, range 15-57) underwent tumor debulking followed by a 90-minute CHPP. CHPP parameters included mean initial CDDP of 120 mu g/mL (range 81-166), perfusate volume 5.2 L (range 4-7), flow 1.5 L/min, intraperitoneal temperature at three locations-41.5 degrees C, 40.5 degrees C, 41.1 degrees C, and core temperature 38.4 degrees C (range 37.2 degrees C-39.5 degrees C). Nine of 10 patients had malignant peritoneal mesothelioma, eight with associated ascites, while the tenth had a symptomatic, multiply recurrent benign peritoneal mesothelioma Nine of 10 patients were optimally debulked. Pharmacokinetics were performed on blood and perfusate samples on nine patients; CDDP levels were quantitated by atomic absorption spectroscopy RESULTS Total perfusate cisplatin AUC was a mean of 21-fold higher (range 2- to 116-fold) than total serum cisplatin AUG, and serum CDDP behaved similarly to systemically administered CDDP. Median follow-up after CHPP is 10 months (range 2-32), with no treatment-related mortality In eight optimally debulked patients there is no evidence of recurrent disease clinically or by CT or MRI. Seven patients with symptomatic ascites have been completely palliated. CONCLUSIONS CHPP with CDDP is well tolerated with no significant regional toxicity. Because favorable CDDP pharmacokinetics suggest the potential for enhanced CDDP tumoricidal effect during CHPP, tumor debulking and CHPP may represent an effective strategy for the treatment of peritoneal mesothelioma. C1 NCI,SURG BRANCH,SURG METAB SECT,NIH,BETHESDA,MD 20892. NCI,CLIN PHARMACOL BRANCH,NIH,BETHESDA,MD 20892. RI Figg Sr, William/M-2411-2016 NR 25 TC 42 Z9 43 U1 0 U2 2 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD MAY-JUN PY 1997 VL 3 IS 3 BP 174 EP 179 PG 6 WC Oncology SC Oncology GA XC487 UT WOS:A1997XC48700009 PM 9161783 ER PT J AU Guo, NH Krutzsch, HC Inman, JK Roberts, DD AF Guo, NH Krutzsch, HC Inman, JK Roberts, DD TI Thrombospondin 1 and type I repeat peptides of thrombospondin 1 specifically induce apoptosis of endothelial cells SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-BETA; HEPARIN-BINDING PEPTIDES; HUMAN BREAST-CANCER; EXTRACELLULAR-MATRIX; SIGNAL-TRANSDUCTION; ADHESION; ANGIOGENESIS; INHIBITION; FIBRONECTIN; ACTIVATION AB Thrombospondin 1 (TSP1) inhibits angiogenesis and modulates endothelial cell adhesion, motility, and growth. The antiproliferative activity of TSP1 is mimicked by synthetic peptides derived from the type I repeats of TSP1 that antagonize fibroblast growth factor 2 and activate latent transforming growth factor beta. These TSP1 analogues induced programmed cell death in bovine aortic endothelial cells based on morphological changes, assessment of DNA fragmentation, and internucleosomal DNA cleavage. Intact TSP1 also induced DNA fragmentation The endothelial cell response was specific because no DNA fragmentation was induced in MDA-MB-435S breast carcinoma cells, although TSP1 and the peptide conjugates inhibited the growth of both cell types. Apoptosis did not depend on activation of latent transforming growth factor beta because peptides lacking the activating sequence RFK were active. Apoptosis was not sensitive to inhibitors of ceramide generation but was inhibited by the phosphatase inhibitor vanadate. Induction of DNA fragmentation by the peptides nas decreased when endothelial cell cultures reached confluence. Growth of the cells on a fibronectin substrate also suppressed induction of apoptosis by TSP1 or the peptides. Differential sensitivities to kinase inhibitors suggest that apoptosis and inhibition of proliferation are mediated by distinct signal transduction pathways. These results demonstrate that induction of apoptosis by the TSP1 analogues is not a general cytotoxic effect and is conditional on a lack of strong survival-promoting signals, such as those provided by a fibronectin matrix. The antitumor activity of TSP1 may therefore result from an increased sensitivity to apoptosis in endothelial cells adjacent to a provisional matrix during formation of vascular beds in tumors expressing TSP1. C1 NIAID,NIH,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 48 TC 226 Z9 232 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1997 VL 57 IS 9 BP 1735 EP 1742 PG 8 WC Oncology SC Oncology GA WW569 UT WOS:A1997WW56900023 PM 9135017 ER PT J AU DeMarini, DM Brooks, LR Bhatnagar, VK Hayes, RB Eischen, BT Shelton, ML Zenser, TV Talaska, G Kashyap, SK Dosemeci, M Kashyap, R Parikh, DJ Lakshmi, V Hsu, F Davis, BB Jaeger, M Rothman, N AF DeMarini, DM Brooks, LR Bhatnagar, VK Hayes, RB Eischen, BT Shelton, ML Zenser, TV Talaska, G Kashyap, SK Dosemeci, M Kashyap, R Parikh, DJ Lakshmi, V Hsu, F Davis, BB Jaeger, M Rothman, N TI Urinary mutagenicity as a biomarker in workers exposed to benzidine: Correlation with urinary metabolites and urothelial DNA adducts SO CARCINOGENESIS LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; N-ACETYLATION PHENOTYPE; BLADDER-CANCER; CIGARETTE SMOKERS; COAL-TAR; HEMOGLOBIN ADDUCTS; PSORIATIC PATIENTS; RUBBER INDUSTRY; BODY-FLUIDS; HUMAN LIVER AB Urinary mutagenicity has been used in occupational and epidemiological studies for over two decades as a cost-effective, general biomarker of exposure to genotoxic agents. However, few studies have compared urinary mutagenicity to additional biomarkers determined among low- and high-exposed groups. To address this issue, we evaluated the relationship between urinary mutagenicity and other types of biomarkers in a cross-sectional study involving 15 workers exposed to the urinary bladder carcinogen benzidine (BZ, high exposure), 15 workers exposed to BZ-dyes (low exposure), and 13 unexposed controls in Ahmedabad, India. Urinary organics were extracted by C18/methanol and evaluated for mutagenicity in the presence of S9 in the Salmonella strain YG1024, which is a frameshift strain that overproduces acetyltransferase. The results were compared to biomarker data reported recently from the same urine samples (Rothman et al., Proc. Natl. Acad. Sci. USA, 93, 5084-5089, 1996) that included a metabolite biomarker (the sum of the urinary levels of BZ + N-acetylbenzidine + N,N'-diacetylbenzidine) and a DNA adduct biomarker [a presumptive N-(3'-phosphodeoxyguanosin-8-yl)-N'-acetylbenzidine (C8dG-ABZ) DNA adduct in exfoliated urothelial cells]. The mean SE urinary mutagenicity (revertants/mu mol of creatinine) of the low-exposure (BZ-dye) workers was 8.2 +/- 2.4, which was significantly different from the mean of the controls (2.8 +/- 0.7, P = 0.04) as was that of the mean of the high-exposure (BZ) workers (123.2 +/- 26.1, P < 0.0001). Urinary mutagenicity showed strong, positive correlations with urinary metabolites (r = 0.88, P < 0.0001) and the level of the presumptive C8dG-ABZ urothelial DNA adduct (r = 0.59, P = 0.0006). A strong association was found between tobacco use (bidi smoking) and urinary mutagenicity among the controls (r = 0.68, P = 0.01) but not among the exposed workers (r = 0.18, P = 0.11). This study confirms the ability of a biomarker such as urinary mutagenicity to detect low-dose exposures, identify additional genotoxic exposures among the controls, and correlate strongly with urinary metabolites and DNA adducts in the target tissue (urinary bladder epithelia) in humans. C1 NATL INST OCCUPAT HLTH,AHMEDABAD,GUJARAT,INDIA. NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. VET ADM MED CTR,ST LOUIS,MO 63125. ST LOUIS UNIV,SCH MED,ST LOUIS,MO 63125. UNIV CINCINNATI,DEPT ENVIRONM HLTH,CINCINNATI,OH 45267. RP DeMarini, DM (reprint author), US EPA,DIV ENVIRONM CARCINOGENESIS,RES TRIANGLE PK,NC 27711, USA. FU NIEHS NIH HHS [1P30-ES-06096-01] NR 71 TC 19 Z9 19 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1997 VL 18 IS 5 BP 981 EP 988 DI 10.1093/carcin/18.5.981 PG 8 WC Oncology SC Oncology GA WZ324 UT WOS:A1997WZ32400015 PM 9163684 ER PT J AU Perkins, SN Hursting, SD Haines, DC James, SJ Miller, BJ Phang, JM AF Perkins, SN Hursting, SD Haines, DC James, SJ Miller, BJ Phang, JM TI Chemoprevention of spontaneous tumorigenesis in nullizygous p53-deficient mice by dehydroepiandrosterone and its analog 16 alpha-fluoro-5-androsten-17-one SO CARCINOGENESIS LA English DT Article ID CELL-EXTRACTS; INHIBITION; DHEA; DEOXYRIBONUCLEOSIDES; LYMPHOPOIESIS; REVERSAL; RATS; P53; DNA AB Transgenic mice with both alleles of the p53 tumor suppressor gene product 'knocked out' by gene targeting are susceptible to early development of tumors, chiefly lymphomas and sarcomas. Compared with the control group, administration of dehydroepiandrosterone (DHEA) at 0.3% of the diet to male p53-deficient mice extended their lifespan by delaying death due to neoplasms (from 105 to 166 days on study, P = 0.002), primarily by suppressing lymphoblastic lymphoma (from 45 to 6% of neoplastic deaths, P = 0.010). Treatment with a synthetic DHEA analog, 16 alpha-fluoro-5-androsten-17-one (compound 8354), at 0.15% of the diet also increased lifespan, to 140 days for mice that developed tumors (P = 0.037). The effects of these steroids on lifespan and tumor development did not appear to be strongly related to inhibition of food consumption and weight gain, in that a group pair-fed with control diet to the reduced food consumption of the DHEA-treated group developed and died of the same types of neoplasms at the same rate as the controls fed ad libitum. The chemopreventive effect of these steroids has been proposed to be due to suppression of DNA synthesis by inhibition of glucose 6-phosphate dehydrogenase, the rate-limiting enzyme of the pentose phosphate pathway. Although DHEA and its analog are strong non-competitive inhibitors of this enzyme in vitro, treatment with DHEA did not deplete cellular nucleotide pools in the liver, as would have been predicted. The chemopreventive effect of DHEA in this model may be due to steroid-induced thymic atrophy and suppression of T cell lymphoma, permitting these mice to survive long enough to develop tumors with longer latency. C1 NCI,LAB NUTR & MOL REGULAT,FREDERICK CANC RES & DEV CTR,SAIC,FREDERICK,MD 21702. NCI,PATHOL HISTOTECHNOL LAB,SAIC,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. NR 22 TC 38 Z9 38 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1997 VL 18 IS 5 BP 989 EP 994 DI 10.1093/carcin/18.5.989 PG 6 WC Oncology SC Oncology GA WZ324 UT WOS:A1997WZ32400016 PM 9163685 ER PT J AU Kelman, DJ Christodoulou, D Wink, DA Keefer, LK Srinivasan, A Dipple, A AF Kelman, DJ Christodoulou, D Wink, DA Keefer, LK Srinivasan, A Dipple, A TI Relative mutagenicities of gaseous nitrogen oxides in the supF gene of pSP189 SO CARCINOGENESIS LA English DT Article ID SINGLE-STRAND BREAKS; NITRIC-OXIDE; ESCHERICHIA-COLI; CELLS; MUTATIONS AB Gaseous nitric oxide (NO), an environmental pollutant found in cigarette smoke and diesel exhaust, has been shown to generate mutations in aerobic in vitro assays. The objective of this study was to identify which oxides of nitrogen, formed in the gaseous phase from NO, possess mutagenic activity. Samples of the plasmid pSP189, in 1 M HEPES buffer, pH 7.4, were exposed to preparations of nitrogen dioxide (NO2), dinitrogen trioxide (N2O3> or an air control. The gas mixtures were formed in a gas-tight syringe and were then introduced into 1 l flasks. The plasmid solution was introduced immediately afterwards. Transformation of Escherichia coli strain MBM7070 with the treated plasmids allowed analysis of mutation frequencies and the types of mutations induced in the target supF gene. The mutation frequency resulting from NO2 exposure was not different from that of the control. However, N2O3 produced a substantial number of mutations. The mutation frequency and the types of mutations were found to depend on the length of time that the gases were allowed to incubate in the syringe prior to introduction into the 1 l flasks (mutation frequency was maximal at approximate to-2 min). The most prevalent mutations were AT-->GC transitions (68%), followed by GC-->AT transitions (30%), similar to previous findings when pure NO was bubbled through pSP189 solutions. These results suggest that it is N2O3, rather than NO2, that is the most likely source of mutagenic potential from gaseous nitrogen oxides. C1 NCI, CHEM CARCINOGENESIS LAB,ABL,BASIC RES PROGRAM, FREDERICK CANC RES & DEV CTR, FREDERICK, MD 21702 USA. NCI, CHEM SECT, COMPARAT CARCINOGENESIS LAB, FREDERICK CANC RES & DEV CTR, FREDERICK, MD 21702 USA. NCI, RADIAT BIOL BRANCH, NIH, BETHESDA, MD 20892 USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 20 TC 4 Z9 5 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1997 VL 18 IS 5 BP 1045 EP 1048 DI 10.1093/carcin/18.5.1045 PG 4 WC Oncology SC Oncology GA WZ324 UT WOS:A1997WZ32400025 PM 9163694 ER PT J AU Tani, M Takenoshita, S Kohno, T Hagiwara, K Nagamachi, Y Harris, CC Yokota, J AF Tani, M Takenoshita, S Kohno, T Hagiwara, K Nagamachi, Y Harris, CC Yokota, J TI Infrequent mutations of the transforming growth factor beta-type II receptor gene at chromosome 3p22 in human lung cancers with chromosome 3p deletions SO CARCINOGENESIS LA English DT Article ID TUMOR-SUPPRESSOR GENE; SMALL-CELL CARCINOMA; MICROSATELLITE INSTABILITY; TGF-BETA; MOLECULAR ANALYSIS; COLORECTAL-CANCER; DNA-SEQUENCE; COLON; HETEROZYGOSITY; ADENOCARCINOMA AB Mutations in the transforming growth factor beta-type II receptor (TGF beta RII) gene have been detected in several types of human cancers that represent the phenotype of genomic instability. The TGF beta RII gene has been mapped to chromosome 3p, on which loss of heterozygosity (LOH) was frequently detected in both small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). To investigate whether the TGF beta RII gene on 3p22 is inactivated in lung cancers, we examined 35 sporadic lung cancers (15 SCLC and 20 NSCLC) with LOH on 3p for mutations of the TGF beta RII gene. We previously produced eight intron based primer pairs for mutational analysis of the entire coding region of the TGF beta RII gene. Using these primers, we screened for mutations of the TGF beta RII gene by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis. A mutation was detected in a case of SCLC: one base insertion in the polyadenine tract of exon 3. This tumor showed the replication error (RER) phenotype. There were no mutations in exons 1, 2, 4, 5, 6 and 7. These results indicate that the polyadenine tract is a mutational hot spot in the TGF beta RII gene in RER positive tumors, and that TGF beta RII mutations occur rarely in lung cancers with LOH on chromosome 3p. C1 NATL CANC CTR,RES INST,DIV BIOL,CHUO KU,TOKYO 104,JAPAN. GUNMA UNIV,SCH MED,DEPT SURG 1,GUNMA 371,JAPAN. NCI,HUMAN CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. NR 31 TC 29 Z9 30 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1997 VL 18 IS 5 BP 1119 EP 1121 DI 10.1093/carcin/18.5.1119 PG 3 WC Oncology SC Oncology GA WZ324 UT WOS:A1997WZ32400036 PM 9163705 ER PT J AU Freed, WJ Isacson, O AF Freed, WJ Isacson, O TI A special issue based on the Third Annual Conference of the American Society for Neural Transplantation, 1996 - Introduction SO CELL TRANSPLANTATION LA English DT Editorial Material C1 HARVARD UNIV,MCLEAN HOSP,NEUROREGENERAT LAB,SCH MED,BELMONT,MA 02178. RP Freed, WJ (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,WASHINGTON,DC 20032, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PD MAY-JUN PY 1997 VL 6 IS 3 BP 201 EP 202 DI 10.1016/S0963-6897(97)00006-7 PG 2 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA XA193 UT WOS:A1997XA19300001 PM 9171152 ER PT J AU Truckenmiller, ME DillonCarter, O Tornatore, C Kulaga, H Takashima, H Freed, WJ AF Truckenmiller, ME DillonCarter, O Tornatore, C Kulaga, H Takashima, H Freed, WJ TI Growth properties of neural cell lines immortalized with the tsA58 allele of SV40 large T antigen SO CELL TRANSPLANTATION LA English DT Article; Proceedings Paper CT 3rd Annual Conference of the American-Society-for-Neural-Transplantation CY APR 25-27, 1996 CL CLEARWATER BEACH, FL SP Amer Soc Neural Transplantat DE temperature-sensitive SV40 large T; tsA58; cell growth; M213-20 cells; immortalization; oncogenes; sequence ID RAT EMBRYO CELLS; SIMIAN-VIRUS 40; NONPERMISSIVE TEMPERATURE; SV40-TRANSFORMED CELLS; PRECURSOR CELLS; GENE; TRANSFORMATION; FRAGMENT; DIFFERENTIATION; ESTABLISHMENT AB In vitro growth properties of three CNS-derived cell lines were compared under a variety of culture conditions, The M213-2O and J30a cell lines were each derived from embryonic CNS culture with the temperature-sensitive (ts) allele of SV40 large T antigen, tsA58, while the A7 cell line was immortalized using wild-type SV40 large T antigen, Cells immortalized with tsA58 SV40 large T proliferate at the permissive temperature, 33 degrees C, while growth is expected to be suppressed at the nonpermissive temperature, 39.5 degrees C, Both the M213-20 and J30a cell lines were capable of proliferating at 39.5 degrees C continuously for up to 6 mo, All three cell lines showed no appreciable differences in growth rates related to temperature over a 7-day period in either serum-containing or defined serum-free media, The percentage of cells in S-phase of the cell cycle did not decrease or was elevated at 39.5 degrees C for all three cell lines, After 3 wk at 39.5 degrees C, the three cell lines also showed positive immunostaining using two monoclonal antibodies reacting with different epitopes of SV40 large T antigen, Double strand DNA sequence analyses of a 300 base pair (bp) fragment of the large T gene from each cell line, which included the ts locus, revealed mutations in both the J30a and M213-2O cell lines, The J30a cell line ts mutation had reverted to wild type, and two additional loci with bp substitutions with predicted amino acid changes were also found, While the ts mutation of the M213-20 cells was retained, an additional bp substitution with a predicted amino acid change was found, The A7 cell line sequence was identical to the reference wild-type sequence. These findings suggest that (a) nucleic acid sequences in the temperature-sensitive region of the tsA58 allele of SV40 large T are not necessarily stable, and (b) temperature sensitivity of cell lines immortalized with tsA58 is not necessarily retained. (C) 1997 Elsevier Science Inc. C1 NINCDS,MOL THERAPEUT SECT,NIH,BETHESDA,MD 20892. RP Truckenmiller, ME (reprint author), NIMH,CTR NEUROSCI,SECT PRECLIN NEUROSCI,2700 MARTIN LUTHER KING JR AVE SE,WASHINGTON,DC 20032, USA. NR 45 TC 9 Z9 9 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PD MAY-JUN PY 1997 VL 6 IS 3 BP 231 EP 238 DI 10.1016/S0963-6897(97)00029-8 PG 8 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA XA193 UT WOS:A1997XA19300005 PM 9171156 ER PT J AU Tornatore, C Rabin, S BakerCairns, B Keir, S Mocchetti, I AF Tornatore, C Rabin, S BakerCairns, B Keir, S Mocchetti, I TI Engraftment of C6-2B cells into the striatum of ACI nude rats as a tool for comparison of the in vitro and in vivo phenotype of a glioma cell line SO CELL TRANSPLANTATION LA English DT Article; Proceedings Paper CT 3rd Annual Conference of the American-Society-for-Neural-Transplantation CY APR 25-27, 1996 CL CLEARWATER BEACH, FL SP Amer Soc Neural Transplantat DE C6-2B cells; ACI nude rats; transplantation; glioma ID GENE-THERAPY; GLIAL-CELLS; IMMUNOLOGICAL CHARACTERISTICS; CONGENITAL APLASIA; MALIGNANT GLIOMAS; BRAIN-TUMORS; EXPRESSION; CULTURE; THYMUS; MODEL AB The C6-2B is a well-characterized glioma cell line used extensively in the study of malignant glial biology, While the C6-2B cell line has traditionally been thought of as a homogenous cell line, the in vitro phenotype of the C6-2B cell line can vary considerably depending on the culture technique used and the stratum on which the cells are grown, Thus, we asked whether the in vitro phenotype of the C6-2B cell line was significantly different than the in vivo phenotype of the cell line once it was engrafted into the striatum of nude rats, Under culture conditions used in our laboratory, 100% of the C6 cells were found to express p75, the low-affinity nerve growth factor (NGF) receptor, and Major Histocompatability Class I(MHC Class I), while only 10-15% demonstrated vimentin reactivity, Immunohistochemistry was consistently negative for GFAP, trkA (the high-affinity receptor for NGF), CD4, CD8, and a macrophage specific marker (Ox-41), Once engrafted into the striatum of nude rats, the cells remained 100% p75 and MHC Class I positive, and again, only 15% of the cells demonstrated vimentin reactivity. The grafted cells retained this characteristic for 28 days in vivo, Although an immunoincompetent host was selected to minimize the effects an inflammatory response would have on the graft, a transient inflammatory response was detected, During the first week of engraftment, numerous MHC class II cells, some of which were macrophages, were seen infiltrating the graft, However, by 4 weeks postengraftment, no inflammatory cells were appreciated in the graft and surprisingly little reactive gliosis was seen in the penumbra of the tumor mass, Thus, the limited number of in vitro phenotypic characteristics we examined in the C6-2B cell line remained constant once the cells were engrafted into the striatum of athymic nude rats. (C) 1997 Elsevier Science Inc. C1 GEORGETOWN UNIV,MED CTR,DEPT CELL BIOL & ANAT,WASHINGTON,DC 20007. NINCDS,LAB MOL MED & THERAPEUT,NIH,BETHESDA,MD 20892. RP Tornatore, C (reprint author), GEORGETOWN UNIV,MED CTR,DEPT NEUROL,1 BLES,3800 RESERVOIR RD NW,WASHINGTON,DC 20007, USA. FU NINDS NIH HHS [NS01675, NS29664] NR 39 TC 8 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PD MAY-JUN PY 1997 VL 6 IS 3 BP 317 EP 326 DI 10.1016/S0963-6897(97)00018-3 PG 10 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA XA193 UT WOS:A1997XA19300013 PM 9171164 ER PT J AU Navaneetham, D Penn, A Howard, J ContiFine, BM AF Navaneetham, D Penn, A Howard, J ContiFine, BM TI Expression of the alpha 7 subunit of the nicotinic acetylcholine receptor in normal and myasthenic human thymuses SO CELLULAR AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 2nd World Congress of Cellular and Molecular Biology CY SEP 03-07, 1996 CL OTTAWA, CANADA DE acetylcholine receptor; alpha 7 subunit; human thymus; myasthenia gravis ID CELL-LINE; MESSENGER-RNAS; PHARMACOLOGICAL PROPERTIES; INTRATHYMIC PATHOGENESIS; MOLECULAR-CLONING; RAT THYMUS; GRAVIS; MUSCLE; ANTIBODIES; PROTEIN AB The nicotinic acetylcholine receptor (AChR) is a transmembrane glycoprotein composed of five homologous subunits. Different isoforms of the AChR alpha subunit exist (alpha 1 to alpha 9). Of them, alpha 1 is expressed in muscle, alpha 2 to alpha 9 in neuronal cells. Muscle AChR is the target autoantigen in the autoimmune disease myasthenia gravis (MG). The thymus is implicated in MG pathogenesis, and the anti-AChR autoimmune response may start in this tissue, that expresses the muscle-type alpha 1 subunit as well as other muscle AChR subunits. The thymus also expresses the ''neuronal'' alpha 3 and alpha 5 subunits. By using polymerase chain reaction and other molecular techniques, we demonstrate here expression of the AChR alpha 7 subunit transcript in thymuses from both myasthenic patients and normal subjects. The alpha 7 subunit can form homo-oligomeric functional AChR complexes that, like muscle AChR, bind alpha-bungarotoxin. The demonstration of expression of the alpha 7 subunit in the thymus suggests that alpha-bungarotoxin binding, functional AChRs of the neuronal type are normally present in the thymus. C1 UNIV MINNESOTA,DEPT BIOCHEM,ST PAUL,MN 55108. UNIV MINNESOTA,DEPT PHARMACOL,MINNEAPOLIS,MN 55455. NINCDS,NIH,OFF DIRECTOR,BETHESDA,MD 20892. UNIV N CAROLINA,DEPT NEUROL,CHAPEL HILL,NC 27599. OI Howard, James/0000-0002-7136-8617 FU NINDS NIH HHS [NS23919] NR 55 TC 14 Z9 14 U1 1 U2 3 PU CELLULAR & MOLECULAR BIOLOGY PI NOISY-LE-GRAND PA PROF R WEGMANN RESIDENCE HAUSSMANN 1 AVENUE DU PAVE NEUF, 93160 NOISY-LE-GRAND, FRANCE SN 0145-5680 J9 CELL MOL BIOL JI Cell. Mol. Biol. PD MAY PY 1997 VL 43 IS 3 BP 433 EP 442 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XD189 UT WOS:A1997XD18900021 PM 9193799 ER PT J AU Stadtman, ER Berlett, BS AF Stadtman, ER Berlett, BS TI Reactive oxygen-mediated protein oxidation in aging and disease SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Review ID METAL-CATALYZED OXIDATION; MIXED-FUNCTION OXIDATION; LOW-DENSITY-LIPOPROTEIN; COLI GLUTAMINE-SYNTHETASE; FREE-RADICAL GENERATION; AMYLOID-BETA-PROTEIN; AMINO-ACID-RESIDUES; AGE-RELATED-CHANGES; HYDROGEN-PEROXIDE; ALZHEIMERS-DISEASE RP Stadtman, ER (reprint author), NHLBI, BIOCHEM LAB, NIH, BLDG 3, ROOM 222, BETHESDA, MD 20892 USA. NR 153 TC 468 Z9 480 U1 11 U2 34 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAY PY 1997 VL 10 IS 5 BP 485 EP 494 DI 10.1021/tx960133r PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA XA008 UT WOS:A1997XA00800002 PM 9168245 ER PT J AU Einolf, HJ Story, WT Marcus, CB Larsen, MC Jefcoate, CR Greenlee, WF Yagi, H Jerina, DM Amin, S Park, SS Gelboin, HV Baird, WM AF Einolf, HJ Story, WT Marcus, CB Larsen, MC Jefcoate, CR Greenlee, WF Yagi, H Jerina, DM Amin, S Park, SS Gelboin, HV Baird, WM TI Role of cytochrome P450 enzyme induction in the metabolic activation of benzo[c]phenanthrene in human cell lines and mouse epidermis SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID REGION DIOL-EPOXIDES; RAT-LIVER MICROSOMES; POLYCYCLIC AROMATIC-HYDROCARBONS; TUMOR-INITIATING ACTIVITY; FEMALE CD RATS; FJORD-REGION; MAMMALIAN-CELLS; MAMMARY CARCINOGENICITY; DNA; BENZO(C)PHENANTHRENE AB The environmental contaminant benzo[c]phenanthrene (B[c]Ph) has weak carcinogenic activity in rodent bioassays; however, the fjord region diol epoxides of B[c]Ph, B[e]Ph-3,4-diol 1,2-epoxides (B[c]PhDE), are potent carcinogens. To determine the role of cytochrome P450 isozymes in the activation of B[c]Ph in MCF-7 cells and the low activation of B[c]Ph in mouse skin, cells of the MCF-7 and the human hepatoma HepG2 cell lines were treated with the potent Ah receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) prior to exposure to B[c]Ph for 24 h. Mice were treated topically with 1 mu g of TCDD or vehicle (control) for 73 h and then with 2 mu mol of B[c]Ph for 24 h. In MCF-7 cells, TCDD exposure increased B[c]PhDE-DNA adduct levels more than S-fold with a 10-fold increase in the (-)-B[c]PhDE-2-dA(t) adduct. Treatment of HepG2 cells with TCDD prior to B[c]Ph application did not increase B[c]PhDE-DNA binding. Total B[c]PhDE-DNA adducts increased 3-fold in TCDD-treated mouse epidermis: the majority of the increase resulted from (+)-B[c]PhDE-1-dA adducts. Analysis of P450 enzymes by Western blotting detected a large increase of P4501B1 but almost no increase in P4501A1 in MCF-7 cells exposed to 10 mu M B[c]Ph for 24 or 48 h. In HepGa cells, there were no detectable levels of P4501A1 or P4501B1 after treatment with 10 mu M B[c]Ph for 24 h. In contrast, topical application of 2 mu mol of B[c]Ph to mouse skin for 48 or 72 h increased P4501A1, but no P4501B1 was detected. As a measure of P450 activity, the metabolism of 7,12-dimethylbenz[a]anthracene (DMBA) was analyzed in microsomes prepared from MCF-7 and HepG2 cells exposed to 0.1% DMSO, 10 mu M B[c]Ph, or 10 mu M TCDD for 24 or 48 h and from mouse epidermis treated with 1 mu g of TCDD, or vehicle control for 72 h, or 2 mu mol of B[c]Ph for 48 h. The levels of DMBA metabolites were low or undetectable in microsomes from B[c]Ph-treated MCF-7 and HepG2 cells, but a metabolite pattern consistent with P4501A1 metabolism of DMBA was present in B[c]Ph-exposed mouse epidermal microsomes. TCDD-treated MCF-7 cells, HepG2 cells, and mouse epidermis had DMBA metabolism patterns characteristic of P4501A1 activity. Microsomes from TCDD-treated human cells formed a higher proportion of the proximate carcinogenic metabolite DMBA-3,4-dihydrodiol (16% of total identified metabolites) than TCDD-treated mouse epidermis (2%). In mouse epidermis, the weak ability of B[c]Ph to increase hydrocarbon-metabolizing activity and the increase in mainly P4501A1, leading to formation of the less carcinogenic stereoisomer B[c]PhDE-1, may explain the low carcinogenic activity of B[c]Ph. In a human mammary carcinoma cell line, treatment with B[c]Ph increases mainly P4501B1 and results in formation of a higher proportion of the more carcinogenic B[c]PhDE-2. This indicates that cells in which B[c]Ph treatment increases P4501B1 levels effectively activate B[c]Ph to potent carcinogenic metabolites. C1 PURDUE UNIV,DEPT MED CHEM & MOL PHARMACOL,W LAFAYETTE,IN 47907. UNIV NEW MEXICO,DEPT PHARMACOL & TOXICOL,ALBUQUERQUE,NM 87131. UNIV WISCONSIN,DEPT PHARMACOL,MADISON,WI 53706. UNIV MASSACHUSETTS,MED CTR,DEPT MOL PHARMACOL & TOXICOL,WORCESTER,MA 01655. NIH,BETHESDA,MD 20892. AMER HLTH FDN,NAYLOR DANA INST DIS PREVENT,VALHALLA,NY 10595. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,MOL CARCINOGENESIS LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA 28825, CA 40228, CA 17613] NR 45 TC 36 Z9 37 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAY PY 1997 VL 10 IS 5 BP 609 EP 617 DI 10.1021/tx960174n PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA XA008 UT WOS:A1997XA00800017 PM 9168260 ER PT J AU Shah, AM Mebazaa, A Yang, ZK Cuda, G Lankford, EB Pepper, CB Sollott, SJ Sellers, JR Robotham, JL Lakatta, EG AF Shah, AM Mebazaa, A Yang, ZK Cuda, G Lankford, EB Pepper, CB Sollott, SJ Sellers, JR Robotham, JL Lakatta, EG TI Inhibition of myocardial crossbridge cycling by hypoxic endothelial cells - A potential mechanism for matching oxygen supply and demand? SO CIRCULATION RESEARCH LA English DT Article DE cardiac contraction; hypoxia; endothelial cell; hibernation; myofilament ID RAT-HEART MYOCYTES; PROTEIN KINASE-C; CARDIAC MYOCYTES; NITRIC-OXIDE; CONTRACTILE FAILURE; BLOOD-FLOW; HYPERTROPHIC CARDIOMYOPATHY; CORONARY VASODILATATION; MUSCLE-CONTRACTION; BETA-MYOSIN AB Previous studies have shown that cardiac endothelial cells release substances that influence myocardial contraction. Since PO2 is an important stimulus that modulates endothelial function, we investigated the effects of acute moderate hypoxia and reoxygenation on the release of cardioactive factors by endothelial cells. Endothelial cells cultured from several vascular beds were superfused with normoxic (equilibrated with room air; PO2, approximate to 160 mm Hg) or hypoxic (PO2, 40 to 50 mm Hg) physiological buffer solution, and the superfusates were reequilibrated to a PO2 of approximate to 160 mm Hg and then tested for their effects on various myocardial assays. Endothelial cell viability and buffer ionic composition were unaltered after the superfusion procedures. The superfusates of hypoxic endothelial cells induced rapid, potent, reversible inhibition of isolated cardiac myocyte contraction without reducing cytosolic Ca2+ transients. This activity was not lost after heating (95 degrees C) and was present in low molecular weight (M-r, <500) superfusate fractions. Hypoxic endothelial superfusate reduced unloaded shortening velocity of human skinned soleus muscle fibers. It markedly depressed in vitro actin motility over cardiac myosin and reduced the rate of actin-activated cardiac myosin ATPase activity but had no effect on corresponding smooth muscle myosin assays. Reoxygenation of hypoxic endothelial cells resulted in loss of this inhibitory activity. These data indicate that cultured endothelial cells respond to acute moderate hypoxia by releasing an unidentified substance(s) that inhibits myocardial crossbridge cycling, independent of Ca2+ or other second messenger signaling pathways. Such a mechanism could have important implications for the regulation of oxygen supply-demand balance in the heart and be relevant to conditions such as myocardial hibernation. C1 NIA,CARDIOVASC SCI LAB,GERONTOL RES CTR,NATL INST HLTH,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,PULM ANESTHESIA LAB,BALTIMORE,MD 21205. NHLBI,MOL CARDIOL LAB,NATL INST HLTH,BETHESDA,MD 20892. UNIV PENN,SCH MED,SCH MED,CARDIOVASC SECT,PHILADELPHIA,PA 19104. LARIBOISIERE HOSP,DEPT ANESTHESIOL,PARIS,FRANCE. RP Shah, AM (reprint author), UNIV WALES COLL MED,DEPT CARDIOL,HEATH PK,CARDIFF CF4 4XN,S GLAM,WALES. RI Cuda, Giovanni/F-5359-2012; OI Cuda, Giovanni/0000-0001-6313-1866; Shah, Ajay/0000-0002-6547-0631 FU NHLBI NIH HHS [R0-1 HL-39138-03] NR 62 TC 32 Z9 33 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD MAY PY 1997 VL 80 IS 5 BP 688 EP 698 PG 11 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA WX256 UT WOS:A1997WX25600010 PM 9130450 ER PT J AU Wyszynski, DF Duffy, DL Beaty, TH AF Wyszynski, DF Duffy, DL Beaty, TH TI Maternal cigarette smoking and oral clefts: A meta-analysis SO CLEFT PALATE-CRANIOFACIAL JOURNAL LA English DT Article DE birth defects; CL/P; congenital malformations; epidemiology; tobacco ID AUTOSOMAL MAJOR LOCUS; CONGENITAL-MALFORMATIONS; PALATE; LIP; PREGNANCY; POPULATION; DEFECTS; SAMPLE; TABLES AB Objective: A meta-analysis was performed to estimate the association between maternal cigarette smoking and the risk of having a child with a nonsyndromic oral cleft (NSOC). Design: Studies published from 1966 through 1996 were retrieved using MEDLINE, Current Contents, bibliographies, and other sources, MEDLINE and Current Contents search terms included ''oral clefts,'' ''cigarette smoking,'' ''birth defects,'' and ''congenital malformations.'' Cohort and case-control studies that enrolled oral cleft patients [cleft lip with or without cleft palate (CL/P), cleft palate (CP), or both] and controls, and presented information on maternal cigarette exposure during pregnancy were included in the analysis, Descriptive and outcome data from each study were independently abstracted by two authors, Results: The overall odds ratio of the 11 studies satisfying criteria was 1.29 [95% confidence interval (CI), 1.18 to 1.42] for CL/P and 1.32 (95% CI: 1.10 to 1.62) for CP indicating a small increased risk of having a child with either a CL/P or a CP for mothers who smoke during the first trimester of the pregnancy. Conclusions: These analyses suggest a small but statistically significant association between maternal cigarette smoking during the first trimester of gestation and increased risk of having a child with a CL/P or CP. C1 NATL HUMAN GENOME RES INST,MED GENET BRANCH,BETHESDA,MD. RP Wyszynski, DF (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,615 N WOLFE ST,BALTIMORE,MD 21205, USA. RI Duffy, David/B-7392-2013 OI Duffy, David/0000-0001-7227-632X FU NIDCR NIH HHS [R01-DE10293] NR 34 TC 108 Z9 121 U1 1 U2 7 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON ON L8N 3K7, CANADA SN 1055-6656 J9 CLEFT PALATE-CRAN J JI Cleft Palate-Craniofac. J. PD MAY PY 1997 VL 34 IS 3 BP 206 EP 210 DI 10.1597/1545-1569(1997)034<0206:MCSAOC>2.3.CO;2 PG 5 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA XA438 UT WOS:A1997XA43800005 PM 9167070 ER PT J AU Lambert, JS Viscidi, R Walker, MC Clayman, B Winget, M Wolff, M Schwartz, DH AF Lambert, JS Viscidi, R Walker, MC Clayman, B Winget, M Wolff, M Schwartz, DH TI Antibody to human immunodeficiency virus type 1 (HIV-1) gp160 in mucosal specimens of asymptomatic HIV-1-infected volunteers parenterally immunized with an experimental recombinant HIV-1 IIIB gp160 vaccine SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID SECRETIONS; IMMUNOGENICITY; RESPONSES; WOMEN; SEMEN; SERUM; RISK; MEN AB Twenty-two human immunodeficiency virus type 1 (HIV-1)-infected, asymptomatic volunteers with CD4 cell counts of > 600 cells/mm(3) who were enrolled in a phase I immunotherapy trial comparing two schedules of immunization of an HIV-1 IIIB-based recombinant gp160 (rgp160) experimental vaccine were evaluated for rgp160-specific antibodies in parotid saliva, genital secretions, and serum, When the study was unblinded, it was determined that five volunteers had received rgp160 on a month 0, 1, 2, 3, 4, and 5 immunization schedule, seven volunteers had received rgp160 on a month 0, 1, 2, and 5 schedule, five had received alum/deoxycholate placebo, and seven had received a licensed hepatitis B virus vaccine, Five volunteers consented to the donation of parotid saliva but not genital secretions, Prior to immunization, parotid saliva specimens were available for 11 of 22 volunteers, seminal plasma (SP) specimens were available for 7 of 22 volunteers, cervicovaginal lavage (CVL) specimens were available for 5 of 22 volunteers, and serum was available for 22 of 22 volunteers, These baseline specimens and specimens collected at 1 and 7 months after the final immunizations were assessed by enzyme-linked immunosorbent assay for immunoglobulin G (IgG) and IgA antibodies specific for HIV-1 LAI rgp160 or HIV-1 MN rgp160, No augmentation in HIV rgp160-specific IgG or IgA antibody production in either parotid saliva or serum specimens of vaccinees compared to that in controls was observed after immunization, There were insufficient numbers of SP or CVL specimens available for statistical comparisons between vaccinees and controls, Overall, anti-LAI rgp160 IgG antibodies were detected in the parotid saliva specimens of 20 of 22 volunteers, the seminal plasma specimens of 11 of 11 volunteers, and the CVL specimens of 6 of 6 volunteers and in 21 of 22 serum specimens, Fen er volunteers expressed anti-LAI rgp160 IgA antibodies in mucosal or serum specimens: 11 of 22 parotid saliva specimens, 3 of 11 SP specimens, 3 of 5 CVL samples, and 12 of 22 sera. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. NIAID,DIV AIDS,NIH,BETHESDA,MD 20892. EMMES CORP,POTOMAC,MD 20854. RP Lambert, JS (reprint author), UNIV MARYLAND,INST HUMAN VIROL,SCH MED,ROOM N548,725 W LOMBARD ST,BALTIMORE,MD 21201, USA. FU NIAID NIH HHS [AI-45205, AI-27565, AI-45207] NR 27 TC 1 Z9 1 U1 0 U2 0 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 MAY PY 1997 VL 4 IS 3 BP 302 EP 308 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WX249 UT WOS:A1997WX24900013 PM 9144368 ER PT J AU GambacortiPasserini, C Bertazzoli, C Dermime, S Scardino, A Schendel, D Parmiani, G AF GambacortiPasserini, C Bertazzoli, C Dermime, S Scardino, A Schendel, D Parmiani, G TI Mapping of HLA class I binding motifs in forty-four fusion proteins involved in human cancers SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-Society-of-Hematology CY DEC 01-05, 1995 CL SEATTLE, WA SP Amer Soc Hematol ID ACUTE MYELOID-LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; CHROMOSOMAL TRANSLOCATION; TRANSCRIPTION FACTOR; MESSENGER-RNA; T-CELLS; GENE; MOLECULES; EXPRESSION; PEPTIDES AB Chromosomal translocations coding for abnormal proteins are present in several human cancers, The junctional region of fusion proteins represents a potential target for a T cell-mediated antitumor response, T lymphocytes recognize antigens in the form of short peptides that must bind to HLA molecules, Different HLA specificities can bind different peptides, thus depicting different ''peptide binding motifs,'' It would be useful to know whether a certain fusion protein presents, within its fusion region, the binding motif(s) for a certain HLA molecule, This information would allow a more focused immunological analysis, Here we present data obtained from the screening of the fusion regions of 44 different fusion proteins for the presence of binding motifs to 34 class I HLA molecules, including all of the most frequently encountered specificities, A total of 201 independent peptides was identified (range, 0-11 peptides/fusion protein), A marked heterogeneity among the 44 different fusion proteins analyzed is evident, For example, the pml/RAR alpha fusion protein present in acute promyelocytic leukemia presents no binding motif (BCR 3) at all or to a single HLA molecule (Cw*0301, BCR 1), Alternatively, the fusion proteins BCR/ABL, ALL1/AF-6, EWS/ATF-1, or NPM/ALK exhibit motifs for several common HLA specificities, Heterogeneity is also present inside a single translocation (in ALL1/ENL, for example, different subtypes match motifs with cumulative frequencies in the population from 108 to 0%), In two cases where the relative frequency of different fusion protein subtypes was available, a tendency toward an inverse relationship between frequency and the percentage of population covered by the identified binding motifs was observed, Peptides with motifs for HLA A*0201, A3, and Cw*0702 were also tested for actual binding using a stabilization assay; 13-40% showed significant HLA binding, using this assay, However, fewer fusion protein-derived peptides bound to HLA A*0201 and A3 than non-fusion protein-derived peptides, These data provide the first list of peptides derived from fusion proteins that may be assessed as potential tumor-specific antigens. C1 NHLBI,BONE MARROW TRANSPLANTAT UNIT,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. NCI,NIH,BETHESDA,MD 20892. UNIV MUNICH,DEPT IMMUNOL,MUNICH,GERMANY. RP GambacortiPasserini, C (reprint author), IST NAZL TUMORI,DIV EXPT ONCOL D,VIA VENEZIAN 1,I-20133 MILAN,ITALY. RI Dermime, Said/C-6235-2009 OI GAMBACORTI PASSERINI, CARLO/0000-0001-6058-515X; Dermime, Said/0000-0002-5526-7496 NR 54 TC 12 Z9 12 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 1997 VL 3 IS 5 BP 675 EP 683 PG 9 WC Oncology SC Oncology GA WY371 UT WOS:A1997WY37100005 PM 9815736 ER PT J AU Kitchen, BJ Balis, FM Poplack, DG OBrien, M Craig, CE Adamson, PC AF Kitchen, BJ Balis, FM Poplack, DG OBrien, M Craig, CE Adamson, PC TI A pediatric Phase I trial and pharmacokinetic study of thioguanine administered by continuous i.v. infusion SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; INTRAVENOUS MERCAPTOPURINE; CHILDHOOD LEUKEMIA; ONCOLOGY-GROUP; 6-MERCAPTOPURINE; 6-THIOGUANINE; METHOTREXATE; CARCINOMA AB Although mercaptopurine is the thiopurine antimetabolite predominantly used in the treatment of childhood acute lymphoblastic leukemia (ALL), thioguanine (TG) is more potent than mercaptopurine in in vitro cytotoxicity studies in human leukemic cell lines and leukemic cells from patients with ALL, We conducted a pediatric Phase I trial of TG administered as a continuous i,v, infusion (CIV), A pharmacokinetically guided dose escalation was performed to define the dose rate of TG required to achieve a steady-state plasma concentration (C-ss) exceeding the target concentration of 1 mu M, and then the maximum tolerated duration of infusion of TG at this dose rate was defined, Eighteen patients (median age, 18 years; range, 4-25 years) with refractory malignancies (16 solid tumors and 2 ALL) were enrolled in this study, The starting dose rate of 10 mg/m(2)/h administered for 24 h achieved an average C-ss of 0.9 mu M (range, 0.7-1.2 mu M). Therefore, the dose rate was escalated to 20 mg/m(2)/h, which achieved an average C-ss of 4.1 mu M (range, 1.0-8.3 mu M). This disproportionate increase in the C-ss of TG suggested a capacity-limited (saturable) elimination process, and a pharmacokinetic model incorporating two compartments with capacity-limited elimination from ,the central compartment was developed to describe the disposition of TG, The TG clearances (derived from model parameters) at the 10- and 20-mg/m(2)/h dose rates were 987 and 608 ml/min/m(2), respectively. Dose-limiting myelosuppression (absolute granulocyte count < 500/mm(3) and platelet count < 25,000/mm(3)) was observed in two of three patients treated with a dose rate of 20 mg/m(2)/h administered for 36 h, Administration of CIV of TG at 20 mg/m(2)/h for 24 h was well tolerated in nine patients, Nonhematological toxicities included nonneutropenic infections and mild, reversible changes in hepatic function tests, The recommended dose rate and duration for CIV of TG is 20 mg/m(2)/h for 24 h. RP Kitchen, BJ (reprint author), NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,10 CTR DR,BETHESDA,MD 20892, USA. NR 24 TC 16 Z9 16 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 1997 VL 3 IS 5 BP 713 EP 717 PG 5 WC Oncology SC Oncology GA WY371 UT WOS:A1997WY37100009 PM 9815740 ER PT J AU Cortazar, P Gazdar, AF Woods, E Russell, E Steinberg, SM Williams, J Ihde, DC Johnson, BE AF Cortazar, P Gazdar, AF Woods, E Russell, E Steinberg, SM Williams, J Ihde, DC Johnson, BE TI Survival of patients with limited-stage small cell lung cancer treated with individualized chemotherapy selected by in vitro drug sensitivity testing SO CLINICAL CANCER RESEARCH LA English DT Article ID COMBINATION CHEMOTHERAPY; COLORIMETRIC ASSAY; CARCINOMA; CHEMOSENSITIVITY; RESISTANCE; ETOPOSIDE; CISPLATIN; REMISSION; TOXICITY AB Our purpose was to study the feasibility of determining individualized chemotherapy regimens by in vitro drug sensitivity testing (DST) for patients with limited-stage small cell lung cancer (SCLC) and to evaluate patient response and survival, Fifty-four previously untreated patients with limited-stage small cell cancer were studied, Fresh tumor specimens for DST were collected, when possible, from patients' biopsies before the start of treatment, The differential staining cytotoxicity assay was used to determine the in vitro sensitivity of the tumor cells to different drugs, From these results, an in vitro best regimen (IVBR), a three-drug combination of previously proven efficacy of seven active drugs in SCLC, was selected, Patients were initially treated with four cycles of etoposide/cisplatin and concurrent radiotherapy, This was followed by four cycles of either individualized chemotherapy regimens based on the results of DST or, when DST results were not available, four cycles of vincristine, doxorubicin, and cyclophosphamide, Eighteen patients (33%) underwent biopsy procedures that provided tissue specimens for DST, The biopsy specimens contained tumor cells in 16 of 18 patients, The median duration from diagnosis to start of treatment was 22 days (range, 4-58 days) for the 18 patients who underwent elective thoracic biopsies compared to 21 days (range, 2-74 days) for members of the group that did not (P-2 = 0.58), Time from thoracic biopsy to initiation of chemotherapy was a median of 4 days (range, 2-22 days), DST was done in 10 patients, and IVBR was administered to 8 patients, The median actuarial survival of 8 patients treated with their IVBR was 38.5 months compared to 19 months for the 46 patients treated with empiric chemotherapy, Selection of individualized chemotherapy regimens is labor intensive but feasible in limited-stage SCLC, Treatment with an individualized IVBR in our patients was associated with prolonged patient survival; however, because of the nature of our study design, other factors could have affected the results. C1 NCI, HEAD LUND CANC BIOL SECT, NAVY MED ONCOL BRANCH, NATL NAVAL MED CTR, BETHESDA, MD 20889 USA. NATL NAVAL MED CTR, DEPT SURG & PATHOL, BETHESDA, MD 20889 USA. NCI, BIOSTAT & DATA MANAGEMENT SECT, BETHESDA, MD 20889 USA. NR 31 TC 31 Z9 31 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 1997 VL 3 IS 5 BP 741 EP 747 PG 7 WC Oncology SC Oncology GA WY371 UT WOS:A1997WY37100013 PM 9815744 ER PT J AU Tolcher, AW OShaughnessy, JA Weiss, RB Zujewski, J Myhand, RC Schneider, E Hakim, F Gress, R Goldspiel, B Noone, MH Brewster, LR Gossard, MR Cowan, KH AF Tolcher, AW OShaughnessy, JA Weiss, RB Zujewski, J Myhand, RC Schneider, E Hakim, F Gress, R Goldspiel, B Noone, MH Brewster, LR Gossard, MR Cowan, KH TI A Phase I study of topotecan followed sequentially by doxorubicin in patients with advanced malignancies SO CLINICAL CANCER RESEARCH LA English DT Article ID DNA TOPOISOMERASE-I; LEUKEMIA GROUP-B; CYTO-TOXICITY; CELL-LINE; CANCER; CAMPTOTHECIN; INHIBITOR; TUMORS AB Inhibitors of topoisomerase I and topoisomerase II have demonstrated synergy when administered sequentially in several tumor models while having a diminished antitumor effect when given concurrently, To explore the potential for clinical sequence-dependent synergy, we instituted a Phase I study of topotecan (a topoisomerase I inhibitor) followed by doxorubicin (a topoisomerase II inhibitor) in patients with advanced malignancies, Thirty-three patients with advanced malignancies or malignancies for whom no standard therapy exists were entered into the study, Topotecan was administered in escalating doses by 72-h continuous infusion on days 1, 2, and 3, followed by a bolus of doxorubicin given on day 5, To explore the hematological toxicity associated with this sequence, bone marrow aspirates were obtained both prior to the topotecan infusion and immediately prior to the doxorubicin in 10 patients to determine by fluorescence-activated cell sorting analysis whether CD34+ cell synchronization was occurring using this sequential schedule, Dose-limiting hematological toxicity occurred at the first dose-level in three of six patients, Therefore, we defined the maximum-tolerated dose (MTD) below our starting dose-level, Further dose-escalation and a new MTD were defined with the addition of granulocyte-colony stimulating factor (G-CSF), The MTD was, therefore, topotecan 0.35 mg/m(2)/day continuous i,v, infusion on days 1, 2, and 3, followed by doxorubicin 45 mg/m(2) on day 5 without G-CSF, whereas the MTD with G-CSF was topotecan 0.75 mg/m(2)/day by 72-h continuous i,v, infusion, followed by doxorubicin 45 mg/m(2) i,v, bolus on day 5, Ten patients with paired bone marrow aspirates obtained before topotecan and before doxorubicin administrations were available for evaluation, In 7 of 10 patients, there was an increase (16.6 +/- 2.9% to 25.0 +/- 3.5%; P < 0.02) in the proportion of CD34+ cells in S-phase 24 h after the topotecan infusion and prior to doxorubicin compared to the pretreatment values, whereas 1 patient had a decrease in the proportion of CD34+ cells in S phase and 2 patients had no change, Topotecan and doxorubicin with this sequence and schedule can be given safely; the dose-limiting toxicity is hematological toxicity. Alterations in the fraction of hematopoietic progenitor CD34+ cells in S-phase may account for the increased granulocytopenia and thrombocytopenia observed at relatively low dose levels of the combination with and without G-CSF. C1 NCI,MED BRANCH,BETHESDA,MD 20892. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. NIH,CTR CLIN,BETHESDA,MD 20892. NR 22 TC 24 Z9 24 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 1997 VL 3 IS 5 BP 755 EP 760 PG 6 WC Oncology SC Oncology GA WY371 UT WOS:A1997WY37100015 PM 9815746 ER PT J AU Golfinos, JG Norman, SA Coons, SW Norman, RA Ballecer, C Scheck, AC AF Golfinos, JG Norman, SA Coons, SW Norman, RA Ballecer, C Scheck, AC TI Expression of the genes encoding myelin basic protein and proteolipid protein in human malignant gliomas SO CLINICAL CANCER RESEARCH LA English DT Article ID NERVOUS-SYSTEM; CELL-LINES; OLIGODENDROGLIOMAS AB Pathological differentiation of oligodendroglioma and mixed oligoastrocytoma from astrocytoma is difficult, relying on morphological characteristics due to the lack of reliable immunohistochemical stains. Oligodendrocytes, the presumed cell of origin of oligodendrogliomas, highly express the genes encoding myelin basic protein (MBP) and proteolipid protein (PLP), We analyzed the expression of these genes to determine whether they might be useful molecular markers of oligodendrocytic tumors, MBP and PLP were highly expressed in all oligodendrogliomas and minimally expressed in glioblastomas multiforme. MBP was highly expressed in mixed oligoastrocytomas, whereas PLP expression was minimal. The association between tumor classification and expression of the MBP and PLP genes was statistically significant. Expression of these genes may serve as a useful molecular marker for some subtypes of human gliomas. C1 ST JOSEPHS HOSP,BARROW NEUROL INST,DIV NEUROSURG,PHOENIX,AZ 85013. ST JOSEPHS HOSP,BARROW NEUROL INST,DIV NEUROPATHOL,PHOENIX,AZ 85013. NIDDKD,NIH,PHOENIX,AZ. FU NCI NIH HHS [CA 50931] NR 25 TC 8 Z9 9 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 1997 VL 3 IS 5 BP 799 EP 804 PG 6 WC Oncology SC Oncology GA WY371 UT WOS:A1997WY37100021 PM 9815752 ER PT J AU Reincke, M Beuschlein, F Latronico, AC Arlt, W Chrousos, GP Allolio, B AF Reincke, M Beuschlein, F Latronico, AC Arlt, W Chrousos, GP Allolio, B TI Expression of adrenocorticotrophic hormone receptor mRNA in human adrenocortical neoplasms: Correlation with P450scc expression SO CLINICAL ENDOCRINOLOGY LA English DT Article ID GROWTH FACTOR-II; ONCOGENIC MUTATIONS; MESSENGER-RNA; NO EVIDENCE; TUMORS; CARCINOMA; PROTEIN; GENE; ACTH AB OBJECTIVE Adrenocorticotrophin (ACTH) is the main hormone-regulating steroid secretion from the adrenal cortex. The ACTH receptor (ACTH-R) has recently been cloned, allowing systematic evaluation of its expression and function in adrenal tumorigenesis. We investigated ACTH-R and P450 side-chain cleavage enzyme (P450scc) mRNA expression in a variety of neoplastic adrenocortical tissues by Northern blot and reverse-transcriptase-PCR (RT-PCR), PATIENTS AND MEASUREMENTS We studied tissue from eight normal adrenals, six diffuse adrenocortical hyperplasias in patients with ACTH-dependent Cushing's syndrome, 22 adrenal adenomas, six carcinomas and two carcinoma cell lines, Poly A mRNA was electrophoresed, immobilized on a nylon membrane and hybridized using alpha(32)P-CTP labelled human ACTH-R and P450scc cDNAs. RESULTS Mean ACTH-R mRNA expression showed significant differences between groups (P = 0.0001), but appeared to be independent of plasma ACTH concentrations, Compared to normal adrenal (= 100 +/- 12%), expression was low in non-functional adenomas (23 +/- 11%) and carcinomas (19 +/- 12%), intermediate in adrenocortical hyperplasias (88 +/- 6%) and cortisol-producing adenomas (81 +/- 15%) and high in aldosteronomas (175 +/- 29%). In adenomas, ACTH-R mRNA expression correlated closely with the expression of P450scc mRNA(r = 0.8, P = 0.0001) suggesting regulation by similar factors. However, carcinomas and cancer cell lines did not show a positive correlation between these two parameters (r = -0.44, P = 0.3). CONCLUSIONS We have demonstrated that plasma ACTH is not the major factor influencing ACTH-receptor mRNA expression in neoplastic adrenal tissue, In benign tumours of the adrenal cortex there was a close positive correlation between ACTH-receptor mRNA and P450scc mRNA which was missing in adrenocortical carcinomas, probably as a result of tumour dedifferentiation. C1 NICHHD, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD USA. RP Reincke, M (reprint author), UNIV WURZBURG, MED KLIN, SCHWERPUNKT ENDOKRINOL, DEPT INTERNAL MED, JOSEF SCHNEIDER STR 2, D-97080 WURZBURG, GERMANY. RI Arlt, Wiebke/B-6310-2009; OI Arlt, Wiebke/0000-0001-5106-9719; Latronico Xavier, Ana Claudia/0000-0001-6782-693X NR 32 TC 50 Z9 50 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD MAY PY 1997 VL 46 IS 5 BP 619 EP 626 DI 10.1046/j.1365-2265.1997.1991009.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XF536 UT WOS:A1997XF53600013 PM 9231058 ER PT J AU Miele, ME DeLaRosa, A Lee, JH Hicks, DJ Dennis, JU Steeg, PS Welch, DR AF Miele, ME DeLaRosa, A Lee, JH Hicks, DJ Dennis, JU Steeg, PS Welch, DR TI Suppression of human melanoma metastasis following introduction of chromosome 6 is independent of NME1 (Nm23) SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE C8161; malignant melanoma; MelJuSo; metastasis suppressor gene; tumor progression ID NUCLEOSIDE DIPHOSPHATE KINASE; HUMAN BREAST-CANCER; REDUCED EXPRESSION; GOOD PROGNOSIS; CELL-LINES; GENE; CARCINOMAS; TUMORIGENICITY; ASSOCIATION; NEOPLASMS AB Metastasis is suppressed more than 95% following microcell-mediated transfer of a single copy of neomycin-tagged human chromosome 6 (neo6) into the human melanoma cell lines C8161 and MelJuSo, Concomitant with metastasis suppression is upregulation of NME1 (Nm23-H1) mRNA and protein expression, The purposes of this study were to determine whether NME1 expression was responsible for metastasis suppression in neo6/melanoma hybrids, and whether genes on chromosome 6 regulate NME1, Using neo6/C8161 cells, transfection of CAT reporter constructs linked to the NME1 promoter failed to consistently induce CAT, Therefore, it does not appear that genes on chromosome 6 directly control transcription of NME1, Transfection and overexpression of NME1 in MelJuSo, under the control of the CMV promoter, resulted in 40-80% inhibition of lung metastasis following i,v, inoculation of 2 x 10(5) cells, Only one transfectant of C8161 subclone 9 (C8161cl.9) cells was suppressed for metastasis. Control transfections,vith pCMVneo or pSV2neo did not suppress metastasis in either cell line, Taken together, these data suggest that NME1 can reduce metastatic potential of some human melanoma cells; but, this inhibitory activity appears to be independent of the metastasis suppression following introduction of chromosome 6 into C8161 and MelJuSo human melanoma cell lines. C1 PENN STATE UNIV,COLL MED,JAKE GITTLEN CANC RES INST C7810,DEPT EXPT PATHOL,HERSHEY,PA 17033. NCI,DIV CLIN SCI,PATHOL LAB,WOMENS CANC SECT,BETHESDA,MD 20892. RI Welch, Danny/B-7310-2009 OI Welch, Danny/0000-0002-1951-4947 FU NCI NIH HHS [CA62168] NR 37 TC 37 Z9 38 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD MAY PY 1997 VL 15 IS 3 BP 259 EP 265 DI 10.1023/A:1018473415458 PG 7 WC Oncology SC Oncology GA WZ311 UT WOS:A1997WZ31100006 PM 9174127 ER PT J AU Mildvan, D Landay, A DeGruttola, V Machado, SG Kagan, J AF Mildvan, D Landay, A DeGruttola, V Machado, SG Kagan, J TI An approach to the validation of markers for use in AIDS clinical trials SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; SYNCYTIUM-INDUCING PHENOTYPE; HIV-INFECTED PATIENTS; T-CELL FUNCTION; PLACEBO-CONTROLLED TRIAL; INTRAVENOUS-DRUG-USERS; ASYMPTOMATIC HOMOSEXUAL MEN; ZIDOVUDINE-TREATED PATIENTS; IMMUNE-DEFICIENCY-SYNDROME AB Dr. Mildvan and coauthors have thoroughly reviewed and documented what is known about the validation of surrogate markers for use in clinical trials, They have proposed a classification system based on the usefulness of available immunologic and virological assays as measures of prognosis, drug activity, and therapeutic efficacy. The latter, a type II marker in the proposed classification, should estimate the proportion of treatment effect explained by change in the marker induced by therapy and, if complete, can substitute for clinical endpoints, HIV clinical trialists have had a long-standing interest in using surrogates for clinical endpoints to facilitate conduct of experimental protocols and to decrease the time and effort required to develop new treatment strategies, The approach outlined in this review by experienced clinicians, biostatisticians, and immunologists provides a framework to evaluate currently available and potential surrogate markers. C1 RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL. HARVARD UNIV,SCH PUBL HLTH,SPAC,BOSTON,MA 02115. US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. NIAID,DIV AIDS,BETHESDA,MD 20892. RP Mildvan, D (reprint author), BETH ISRAEL MED CTR,DIV INFECT DIS,1ST AVE & 16TH ST,NEW YORK,NY 10003, USA. FU NIAID NIH HHS [5U01-AI27667-11] NR 184 TC 52 Z9 55 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY PY 1997 VL 24 IS 5 BP 764 EP 774 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WX257 UT WOS:A1997WX25700002 PM 9142767 ER PT J AU Fischer, SH Masur, H AF Fischer, SH Masur, H TI Editorial response: Laboratory monitoring of cytomegalovirus disease - Is polymerase chain reaction the answer? SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID TRANSPLANT RECIPIENTS C1 NIH,DEPT CRIT CARE MED,CTR CLIN,BETHESDA,MD 20892. NIH,DEPT CLIN PATHOL,CLIN MICROBIOL SECT,BETHESDA,MD 20892. NR 7 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 MAY PY 1997 VL 24 IS 5 BP 841 EP 842 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WX257 UT WOS:A1997WX25700014 PM 9142779 ER PT J AU Piscitelli, SC Reiss, WG Figg, WD Petros, WP AF Piscitelli, SC Reiss, WG Figg, WD Petros, WP TI Pharmacokinetic studies with recombinant cytokines - Scientific issues and practical considerations SO CLINICAL PHARMACOKINETICS LA English DT Review ID COLONY-STIMULATING FACTOR; AUTOLOGOUS BONE-MARROW; NECROSIS-FACTOR RECEPTORS; HEPATIC DRUG-METABOLISM; HIGH-DOSE CHEMOTHERAPY; FETAL-RAT HEPATOCYTES; ERYTHROPOIETIN PRODUCTION; INTERFERON-GAMMA; CLINICAL PHARMACOKINETICS; HUMAN INTERLEUKIN-2 AB Advances in molecular biology and recombinant DNA technology have led to the development of cytokines as therapeutic agents for a variety of disease states. The pharmacokinetic analysis of cytokines involves the understanding of analytical methods capable of detecting these agents in biological fluids and recognition of several factors which may have an impact on the cytokine concentration-time curves. Enzyme-linked immunosorbent assays (ELISA) have become the most common method of detection and commercial kits are available for a wide variety of cytokines. Monoclonal antibody products are sensitive, have minimal crossreactivity and are relatively inexpensive when compared with high performance liquid chromatography (HPLC). However, the primary limitation of these assays is their inability to measure biologically active protein. Conversely, bioassays do measure a biological event (i.e. proliferation or cytotoxicity) but are generally not used for cytokine analysis because of their high cost, long assay completion time, lack of specificity, poor sensitivity and influence of environmental conditions on the outcome. The pharmacokinetic profile of recombinant cytokines is influenced by a number of variables: endogenous production, circulating soluble receptors and cell-associated receptors, immunocompetence and antibody production against the cytokine all may influence the disposition of the agent. Thus, pharmacokinetic modelling of cytokines may involve complex models capable of characterising these nonlinear processes and resulting effects. The route of administration is an important variable since cytokines administered by subcutaneous injection may be partially metabolised by proteases present in the subcutaneous tissue. Other methods to simplify cytokine delivery are being actively investigated and include formulations for inhalation, topical and oral administration. A variety of cytokines (including interferon-alpha, interleukin-6 and tumour necrosis factor) are capable of inhibiting cytochrome P450 hepatic enzymes and, therefore, possess the potential to cause drug-cytokine interactions. Inhibition has been demonstrated in several in vitro systems and animal models, although clinical data are currently limited. An increased understanding of the many factors which can alter the analysis and pharmacokinetics of cytokines is essential to the design of optimal dosage regimens. C1 UNIV MARYLAND,SCH PHARM,DEPT PHARM PRACTICE & SCI,BALTIMORE,MD 21201. NCI,CLIN PHARMACOKINET SECT,CLIN PHARMACOL BRANCH,DIV CLIN SCI,BETHESDA,MD 20892. DUKE UNIV,MED CTR,BONE MARROW TRANSPLANT PROGRAM,CLIN PHARMACOL LAB,DURHAM,NC. RP Piscitelli, SC (reprint author), NIH,CLIN PHARMACOKINET RES LAB,CTR CLIN,DEPT PHARM,BLDG 10,RM 1N257,BETHESDA,MD 20892, USA. RI Figg Sr, William/M-2411-2016 NR 79 TC 34 Z9 34 U1 0 U2 2 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0312-5963 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PD MAY PY 1997 VL 32 IS 5 BP 368 EP 381 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WZ608 UT WOS:A1997WZ60800003 PM 9160171 ER PT J AU Stefanski, R Goldberg, SR AF Stefanski, R Goldberg, SR TI Serotonin 5-HT2 receptor antagonists - Potential in the treatment of psychiatric disorders SO CNS DRUGS LA English DT Review ID OBSESSIVE-COMPULSIVE DISORDER; GENERALIZED ANXIETY DISORDER; MEDIAL PREFRONTAL CORTEX; ELEVATED PLUS-MAZE; SLOW-WAVE SLEEP; CHRONIC-SCHIZOPHRENIC PATIENTS; NEUROLEPTIC INDUCED AKATHISIA; ANTI-DEPRESSANT TREATMENT; RAT STOMACH FUNDUS; DOUBLE-BLIND TRIAL AB This review highlights recent pharmacological and clinical advances in the understanding of the potential use of serotonin 5-HT2 receptor antagonists as treatments for a number of psychiatric disorders, namely anxiety, depression and schizophrenia. 5-HT2 receptor antagonists have not vet been clearly demonstrated to be effective in humans as treatments for anxiety, Some preliminary clinical trials suggest that the 5-HT2 receptor antagonist ritanserin may have a beneficial effect in patients with generalised anxiety disorder, but the evidence is far from compelling. Upregulation of central 5-HT2 receptors anti an accompanying increase in phosphoinositide turnover appear to be predisposing biological factors in depression. A functional interaction between 5-HT1A and 5-HT2 receptors mac be of particular importance, since 5-HT2 receptor antagonism can ultimately result in a facilitation of 5-HT1A receptor-mediated neurotransmission and this may be beneficial for the treatment of depression, Ritanserin appears to be more effective than placebo in alleviating the depressive symptoms of dysthymia. Nefazodone is a nets antidepressant that combines 5-HT2 receptor blockade with serotonin reuptake inhibition, Comparisons with imipramine favour nefazodone in terms of tolerability and suggest that both drugs are equally clinical effective, In schizophrenia, 5-HT2A receptor function appears to be altered. Modulation of dopaminergic function via 5-HT2A receptors may provide a viable mechanism for enhancing the effect of antipsychotics. Risperidone, the first post-clozapine agent that has 5-HT2A and dopamine D-2 receptor antagonist actions, is at least as effective as haloperidol and perphenazine in reducing acute psychotic symptoms. Its major clinical advantages are a greater efficacy in controlling the secondary negative symptoms and a lower incidence of extrapyramidal symptoms (EPS). The efficacy of ritanserin in alleviating both positive and negative symptoms in acutely psychotic patients stems to support thr hypothesis that potent 5-HT2A receptor antagonism alone may contribute to the therapeutic action of several clinically effective antipsychotics that have reduced liability to induce EPS. RP Stefanski, R (reprint author), NIDA,PRECLIN PHARMACOL LAB,NIH,INTRAMURAL RES PROGRAM,POB 5180,BALTIMORE,MD 21224, USA. NR 224 TC 11 Z9 12 U1 1 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PD MAY PY 1997 VL 7 IS 5 BP 388 EP 409 PG 22 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA XA190 UT WOS:A1997XA19000006 ER PT J AU Kelley, CA AF Kelley, CA TI Characterization of isoform diversity among smooth muscle and nonmuscle myosin heavy chains SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article DE myosin II; myosin heavy chains; smooth muscle; nonmuscle; isoforms; phosphorylation; meiosis; Xenopus ID MESSENGER-RNAS; VASCULAR DEVELOPMENT; CDNA CLONING; B ISOFORM; CELLS; IDENTIFICATION; EXPRESSION; CHICKEN; REGION; KINASE AB In the last decade, as a result of molecular cloning and the reverse-transcriptase polymerase chain reaction, numerous isoforms of the contractile protein myosin have been discovered. What lags behind their discovery is knowledge of their functions. This review focuses on some of my recent work on the structure, function and regulation of isoforms of the heavy chain of vertebrate smooth muscle and nonmuscle myosin II. Reference to related work in the field is included where appropriate. The particular isoforms discussed are those that are generated by alternative splicing near the 5' end of the pre-mRNA, resulting in either an insertion or a deletion of a cassette of amino acids near the amino-terminus of the myosin heavy chain (MHC) protein. In both the smooth muscle and nonmuscle MHCs, this splicing occurs in the exact same region, which begins at amino acid 212 in the primary sequence. In the Three-dimensional structure of the molecule, these inserts are located near the ATP-binding pocket in a region of the MHC that was not resolved in the crystal structure and therefore is believed to represent a flexible loop. In the smooth muscle MHC, the insertion of seven amino acids in this loop confers a higher enzymatic activity on the myosin. The potential mechanism by which this occurs and the significance to smooth muscle contractile diversity is discussed. In the nonmuscle MHC, the insert in this region is a different size and sequence of amino acids than that in the smooth muscle MHC. A serine residue (Ser-214) in the nonmuscle loop is phosphorylated by p34(cdc2) kinase in Xenopus during meiotic maturation of oocytes to eggs and is dephosphorylated in interphase egg extracts that are equivalent to the interphase after fertilization of the egg. Thus, MHC-B phosphorylation by cdc2 kinase correlates with the cortical reorganization that occurs during meiosis, and dephosphorylation correlates with the cortical contraction that occurs at fertilization, which aids in pronuclear fusion. In summary, these inserts in the MHC molecule, in a flexible loop near the ATP-binding pocket, appear to be important in determining differences in function or regulation among myosin II isoforms. (C) 1997 Elsevier Science Inc. RP Kelley, CA (reprint author), NHLBI, MOL CARDIOL LAB, NIH, BLDG 10, ROOM 8N-202, BETHESDA, MD 20892 USA. NR 39 TC 12 Z9 12 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0305-0491 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD MAY PY 1997 VL 117 IS 1 BP 39 EP 49 DI 10.1016/S0305-0491(96)00313-6 PG 11 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA WX438 UT WOS:A1997WX43800006 PM 9180013 ER PT J AU Woodward, RA Weld, KP AF Woodward, RA Weld, KP TI A comparison of ketamine, ketamine-acepromazine, and tiletamine-zolazepam on various hematologic parameters in rhesus monkeys (Macaca mulatta) SO CONTEMPORARY TOPICS IN LABORATORY ANIMAL SCIENCE LA English DT Article AB A comparison was made of the complete blood cell count, immunohematologic, and serum biochemical values in 18 rhesus monkeys that were immobilized with ketamine, ketamine-acepromazine, or tiletamine-zolazepam. Significant differences were not found among the hematologic variables evaluated while monkeys were under anesthesia induced by use of the 3 anesthetic agents, except for serum potassium concentrations. Although the potassium values were significantly different, values remained within the established normal range of the reference laboratory for rhesus macaques (Macaca mulatta). Tiletamine-zolazepam did not significantly alter the complete blood cell count, immunohematologic, or serum biochemical values. It may be preferable, because it provides increased analgesia and muscle relaxation in nonhuman primates, compared with ketamine or ketamine/ acepromazine. C1 NIAAA,NIH,POOLESVILLE,MD. RP Woodward, RA (reprint author), ADV BIOSCI LABS INC,VET RESOURCES,KENSINGTON,MD 20895, USA. NR 7 TC 9 Z9 9 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 1060-0558 J9 CONTEMP TOP LAB ANIM JI Contemp. Top. Lab. Anim. Sci. PD MAY PY 1997 VL 36 IS 3 BP 55 EP 57 PG 3 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA XD250 UT WOS:A1997XD25000010 PM 16450955 ER PT J AU Hagedorn, M Kleinhans, FW Wildt, DE Rall, WF AF Hagedorn, M Kleinhans, FW Wildt, DE Rall, WF TI Chill sensitivity and cryoprotectant permeability of dechorionated zebrafish embryos, Brachydanio rerio SO CRYOBIOLOGY LA English DT Article ID FISH EMBRYOS; DIMETHYLSULFOXIDE; CRYOPRESERVATION; PRESERVATION; SPERMATOZOA; METHANOL; INTACT; WATER; CELLS AB The zebrafish (Brachydanio rerio) was used as a model for basic studies of the chilling sensitivity, permeability and toxicity of cryoprotectants. In both intact and dechorionated embryos, early stage embryos (1.25, 1.5, 1.75, and 2 h) were more susceptible (P < 0.05) to chilling injury at 0 degrees C than late-stage embryos (50, 75, and 100% epiboly and three-somite stage). Moreover, enzymatic removal of the chorion did not alter (P > 0.05) this pattern of sensitivity to chilling. Eight-hour zebrafish embryos tolerated short-term exposures to temperatures ranging from 4 to 23 degrees C for 3.5 h with no detrimental developmental effects. The permeability of dechorionated embryos to cryoprotectants was examined by measuring the kinetics of volumetric change at various develop mental stages (16 cells to six somites or ca 1.25 to 14 h postfertilization) at 28.5 degrees C. The dechorionated zebrafish embryo is composed of two complex cellular compartments (i.e., a large yolk and the developing blastoderm). From 40 to 100% epiboly, the volumes of the yolk and blastoderm remained constant, ca 82 and 18%, respectively. However, these volumes changed rapidly after epiboly. For example, at the six-somite stage, the yolk composed 61% of the total volume, whereas the blastoderm composed 39%. When three- and six-somite embryos were placed in 1.5 and 2.0 M cryoprotectants (dimethyl sulfoxide and propylene glycol), osmometric measurement of volume changes indicated no permeation of the cryoprotectants. However, some permeation was observed for six-somite embryos immersed in a 2.0 M methanol solution, but not for 3-somite embryos. For up to 30 min at room temperature, these cryoprotectant solutions were not toxic to zebrafish embryos; however, 1.5 M glycerol and ethylene glycol solutions were. We conclude that the complex nature of the zebrafish embryo reduces the effectiveness and predictive value of light microscopical measurements for cryoprotectant permeability studies. (C) 1997 Academic Press. C1 SMITHSONIAN INST, CONSERVAT & RES CTR, WASHINGTON, DC 20008 USA. INDIANA UNIV PURDUE UNIV, DEPT PHYS, INDIANAPOLIS, IN 46202 USA. NIH, VET RESOURCES PROGRAM, NATL CTR RES RESOURCES, BETHESDA, MD 20892 USA. RP Hagedorn, M (reprint author), SMITHSONIAN INST, NATL ZOOL PK, WASHINGTON, DC 20008 USA. RI Rall, William/C-5104-2008 FU NCRR NIH HHS [R29 RR08769] NR 42 TC 71 Z9 74 U1 0 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0011-2240 J9 CRYOBIOLOGY JI Cryobiology PD MAY PY 1997 VL 34 IS 3 BP 251 EP 263 DI 10.1006/cryo.1997.2002 PG 13 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA WZ400 UT WOS:A1997WZ40000005 PM 9160996 ER PT J AU Guo, J Sax, CM Piatigorsky, J Yu, FSX AF Guo, J Sax, CM Piatigorsky, J Yu, FSX TI Heterogeneous expression of transketolase in ocular tissues SO CURRENT EYE RESEARCH LA English DT Article DE transketolase; wound healing; differentiation; stratification; corneal crystallin; antioxidative damage ID CORNEAL ALDEHYDE DEHYDROGENASE; STRATIFIED SQUAMOUS EPITHELIUM; WERNICKE-KORSAKOFF-SYNDROME; ADENYLATE-CYCLASE ACTIVITY; EXTRACELLULAR-MATRIX; PROTEIN; CELLS; ABNORMALITY; FIBROBLASTS; GENETICS AB Purpose. Previous studies have shown that transketolase is preferentially expressed in the corneal epithelium and comprises up to 10% of the soluble protein of the mature mouse cornea. The aim of this study is to evaluate the expression and distribution of TKT in the different ocular tissues. Methods. We have used in situ hybridization and immunohistochemistry to localize TKT mRNA and protein in the developing and adult mouse eye. Results. TKT were found to be widely distributed throughout the adult mouse eye. Among the ocular tissues examined, the corneal epithelium exhibited the highest levels of TKT mRNA and protein. Within the epithelial layer, TKT mRNA and protein were differentially distributed with the highest expression occurring in basal cells and the lowest in apical cells, suggesting that TKT expression in the corneal epithelium may be differentiation-related. Enriched expression of TKT was also found in the cornea endothelium, lens epithelium, ciliary body, and iris. Low basal levels of expression were observed in the limbus and conjunctiva. In contrast to the adult eye, TKT expression in the one-day-old mouse eye was homogeneous at low, but detectable levels, suggesting that TKT expression is developmentally regulated in the cornea as well as in the other ocular tissues. In the healing corneal epithelium, TKT expression in the single cell layer of the leading edge was completely suppressed until the cells began to stratify, at which point TKT expression increased markedly. Conclusions. The results presented here suggest that TKT is differentially expressed and developmentally regulated in the various tissues that comprise the eye. C1 HARVARD UNIV,SCH MED,SCHEPENS EYE RES INST,BOSTON,MA 02114. NEI,MOL & DEV BIOL LAB,NIH,BETHESDA,MD. FU NEI NIH HHS [EY10869] NR 42 TC 17 Z9 18 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD MAY PY 1997 VL 16 IS 5 BP 467 EP 474 DI 10.1076/ceyr.16.5.467.7042 PG 8 WC Ophthalmology SC Ophthalmology GA WW327 UT WOS:A1997WW32700009 PM 9154385 ER PT J AU Nwachuku, CE Cutler, JA AF Nwachuku, CE Cutler, JA TI The explosion of morbidity and mortality trials in hypertension SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review ID ISOLATED SYSTOLIC HYPERTENSION; BLOOD-PRESSURE; MYOCARDIAL-INFARCTION; PROGRESS REPORT; OLDER PATIENTS; ELDERLY TRIAL; EUR TRIAL; REGRESSION; RISK AB The highlights of each generation of hypertension trials have been varied, but interrelated, The initial hypertension trials focused on middle-aged hypertensive individuals and later on the elderly, with emphasis on diastolic blood pressure and subsequently on systolic blood pressure. Past generations of trials elucidated whether and whom to treat, The current explosion of morbidity and mortality trials in hypertension largely seeks to learn what drugs should be used and to delineate what blood pressure goals should be targeted. RP Nwachuku, CE (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,NIH,TWO ROCKLEDGE CTR,6701 ROCKLEDGE DR,BETHESDA,MD 20892, USA. NR 44 TC 4 Z9 4 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD MAY PY 1997 VL 6 IS 3 BP 230 EP 236 DI 10.1097/00041552-199705000-00006 PG 7 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA XK273 UT WOS:A1997XK27300006 PM 9263665 ER PT J AU Warren, KR Vanderveen, E Adamson, MD AF Warren, KR Vanderveen, E Adamson, MD TI Alcohol and risk behavior SO CURRENT OPINION IN PSYCHIATRY LA English DT Article ID SEXUAL-BEHAVIOR; SUBSTANCE USE; YOUNG-ADULTS; PERCEPTIONS; DRINKING AB Much of the recent research on alcohol and risk behaviors has been directed at elucidating causality and linkage mechanisms. Some findings suggest judgment is not necessarily lost with drinking. Significant achievements are the reports of two successful multicomponent community prevention studies. RP Warren, KR (reprint author), NIAAA,NIH,WILLCO BLDG SUITE 409,6000 EXECUT BLVD,MSC 7003,BETHESDA,MD 20892, USA. NR 36 TC 1 Z9 1 U1 1 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD MAY PY 1997 VL 10 IS 3 BP 211 EP 214 DI 10.1097/00001504-199705000-00006 PG 4 WC Psychiatry SC Psychiatry GA XA835 UT WOS:A1997XA83500006 ER PT J AU Kaltenbach, K Finnegan, L AF Kaltenbach, K Finnegan, L TI Children of maternal substance misusers SO CURRENT OPINION IN PSYCHIATRY LA English DT Article ID COCAINE USE; FETAL GROWTH; PRENATAL EXPOSURE; MARIJUANA USE; PREGNANCY; ALCOHOL; BEHAVIOR; SMOKING; INFANTS; RECOGNITION AB This review examines recent research investigating the effects of prenatal exposure to tobacco, alcohol, cocaine, or marijuana. Findings are discussed in terms of their implications and also within the context of methodological problems prevalent in the literature, especially in studies investigating exposure to illicit drugs. C1 NIH,WOMENS HLTH INITIAT,BETHESDA,MD 20892. RP Kaltenbach, K (reprint author), THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PEDIAT,1201 CHESTNUT ST,9TH FLOOR,PHILADELPHIA,PA 19107, USA. NR 56 TC 1 Z9 1 U1 1 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD MAY PY 1997 VL 10 IS 3 BP 220 EP 224 DI 10.1097/00001504-199705000-00008 PG 5 WC Psychiatry SC Psychiatry GA XA835 UT WOS:A1997XA83500008 ER PT J AU Kaneko, KJ Cullinan, EB Latham, KE DePamphilis, ML AF Kaneko, KJ Cullinan, EB Latham, KE DePamphilis, ML TI Transcription factor mTEAD-2 is selectively expressed at the beginning of zygotic gene expression in the mouse SO DEVELOPMENT LA English DT Article DE TEF-1; mouse preimplantation embryo; oocyte; gene expression; TEA DNA binding domain; TEAD gene family ID ENHANCER FACTOR-I; PREIMPLANTATION EMBRYOS; PROMOTER ACTIVITY; PROTEIN; TEF-1; OOCYTES; CELLS; MICE; DNA; REPRESSION AB mTEF-1 is the prototype of a family of mouse transcription factors that share the same TEA DNA binding domain (mTEAD genes) and are widely expressed in adult tissues, At least one member of this family is expressed at the beginning of mouse development, because mTEAD transcription factor activity was not detected in oocytes, but first appeared at the 2-cell stage in development, concomitant with the onset of zygotic gene expression, Since embryos survive until day II in the absence of mTEAD-1 (TEF-1), another family member likely accounts for this activity, Screening an EC cell cDNA library yielded mTEAD-1, 2 and 3 genes, RT-PCR detected RNA from all three of these genes in oocytes, but upon fertilization, mTEAD-1 and 3 mRNAs disappeared, mTEAD-2 mRNA, initially present at approx, 5,000 copies per egg, decreased to approx, 2,000 copies in 2-cell embryos before accumulating to approx. 100,000 copies in blastocysts, consistent with degradation of maternal mTEAD mRNAs followed by selective transcription of mTEAD-2 from the zygotic genome, In situ hybridization did not detect mTEAD RNA in oocytes, and only mTEAD-2 was detected in day-7 embryos, Northern analysis detected all three RNAs at varying levels in day-9 embryos and in various adult tissues, A fourth mTEAD gene, recently cloned from a myotube cDNA library, was not detected by RT-PCR in either oocytes or preimplantation embryos, Together, these results reveal that mTEAD-2 is selectively expressed for the first 7 days of embryonic development, and is therefore most likely responsible for the mTEAD transcription factor activity that appears upon zygotic gene activation. C1 NICHHD,NIH,BETHESDA,MD 20892. HOFFMANN LA ROCHE INC,ROCHE RES CTR,NUTLEY,NJ 07110. TEMPLE UNIV,SCH MED,FELS INST CANC RES & MOL BIOL,PHILADELPHIA,PA 19140. TEMPLE UNIV,SCH MED,DEPT BIOCHEM,PHILADELPHIA,PA 19140. NR 40 TC 65 Z9 68 U1 1 U2 7 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD MAY PY 1997 VL 124 IS 10 BP 1963 EP 1973 PG 11 WC Developmental Biology SC Developmental Biology GA XD825 UT WOS:A1997XD82500012 PM 9169843 ER PT J AU Deng, CX Bedford, M Li, CL Xu, XL Yang, X Dunmore, J Leder, P AF Deng, CX Bedford, M Li, CL Xu, XL Yang, X Dunmore, J Leder, P TI Fibroblast growth factor receptor-1 (FGFR-1) is essential for normal neural tube and limb development SO DEVELOPMENTAL BIOLOGY LA English DT Article ID APICAL ECTODERMAL RIDGE; CENTRAL-NERVOUS-SYSTEM; EMBRYONIC STEM-CELLS; EXPRESSION PATTERN; MESODERM FORMATION; MOUSE EMBRYO; DEFECTS; GASTRULATION; TAIL; GENE AB Fibroblast growth factor receptor-1 (FGFR-1) is a membrane-spanning tyrosine kinase that serves as a high-affinity receptor for fibroblast growth factors. It has recently been shown that FGER-1 mutant embryos die during gastrulation displaying severe growth retardation and defective mesodermal structures. This early lethality has obscured functions of FGFR-1 that might occur later in development. To circumvent these embryonic defects, we generated chimeras by injecting FGFR-1-deficient (R1(-/-)) ES cells into wild-type blastocysts. We found that the fgfr-1 gene plays an important role after gastrulation and that it acts in a cell-autonomous fashion. Embryos with a high contribution of R1(-/-) cells replicate the FGFR-1 null phenotype and die during gastrulation. In contrast, the majority of embryos with a low contribution of R1(-/-) cells complete gastrulation and display malformations of posterior structures at later stages of embryogenesis. These abnormalities include truncation of embryonic structures, limb bud malformation, partial duplication of the neural tube, tail distortion, and spina bifida caused by the amplification of neural tissue in the posterior portion of the spinal cord. Thus, FGFR-1 plays a role in neurulation, suggesting that there may be a connection between FGFR-1-mediated signal pathways and neural tube defects, the most common malformations in the human central nervous system. (C) 1987 Academic Press. C1 HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. RP Deng, CX (reprint author), NIDDKD,BIOCHEM & METAB LAB,NIH,BLDG 10,9N105,BETHESDA,MD 20892, USA. RI Bedford, Mark/E-7856-2011; deng, chuxia/N-6713-2016 NR 49 TC 108 Z9 111 U1 0 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAY 1 PY 1997 VL 185 IS 1 BP 42 EP 54 DI 10.1006/dbio.1997.8553 PG 13 WC Developmental Biology SC Developmental Biology GA XA021 UT WOS:A1997XA02100005 PM 9169049 ER PT J AU Smith, U Carvalho, E Wang, LM Pierce, J Rondinone, C AF Smith, U Carvalho, E Wang, LM Pierce, J Rondinone, C TI IRS-2 is the main docking protein for insulin-stimulated PI3-kinase binding and activation in NIDDM. SO DIABETES LA English DT Meeting Abstract C1 SAHLGRENS UNIV HOSP,INST INTERNAL MED,LUNDBERG LAB DIABET RES,GOTHENBURG,SWEDEN. NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 1997 VL 46 SU 1 BP 105 EP 105 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WX380 UT WOS:A1997WX38000105 ER PT J AU Tataranni, P Pratley, RE AF Tataranni, P Pratley, RE TI Higher total body bone mineral density in middle age Pimas vs Caucasians is not related to hyperinsulinemia. SO DIABETES LA English DT Meeting Abstract C1 NIDDK,CDNS,NIH,PHOENIX,AZ. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 1997 VL 46 SU 1 BP 967 EP 967 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WX380 UT WOS:A1997WX38000964 ER PT J AU Eastman, RC Javitt, JC Herman, WH Dasbach, EJ Zbrozek, AS Dong, F Manninen, D Garfield, SA CopleyMerriman, C Maier, W Eastman, JF Kotsanos, J Cowie, CC Harris, M AF Eastman, RC Javitt, JC Herman, WH Dasbach, EJ Zbrozek, AS Dong, F Manninen, D Garfield, SA CopleyMerriman, C Maier, W Eastman, JF Kotsanos, J Cowie, CC Harris, M TI Model of complications of NIDDM .1. Model construction and assumptions SO DIABETES CARE LA English DT Article ID DIABETES-MELLITUS; PIMA-INDIANS; POPULATION; ROCHESTER; RETINOPATHY; PROTEINURIA; PREVALENCE; DIAGNOSIS; MINNESOTA; MORTALITY AB OBJECTIVE - To develop a model of NIDDM for analyzing prevention strategies for NIDDM. RESEARCH DESIGN AND METHODS - A Markov type model with Monte Carlo techniques was used. Age, sex, and ethnicity of cohort was based on U.S. data. Incidence rates of complications were also based on community and population studies. RESULTS - Nonproliferative retinopathy, proliferative retinopathy, and macular edema are predicted in 79, 19, and 52%, respectively, of people with NIDDM; 19% are predicted to develop legal blindness. Microalbuminuria, gross proteinuria, and end-stage renal disease related to diabetes are predicted in 53, 40, and 17%, respectively. Symptomatic sensorimotor neuropathy and lower-extremity amputation are predicted in 31 and 17%, respectively. Cardiovascular disease is predicted in 39%. Higher rates of complications (1.1-3.0X) are predicted in minority populations. Predicted average life expectancy is 17 years after diagnosis. CONCLUSIONS - A probabilistic model of NIDDM predicts the vascular complications of NIDDM in a cohort representative of the incident cases of diabetes in the U.S. before age 75 years. Predictions of complications and mortality are consistent with the known epidemiology of NIDDM. The model is suitable for evaluating the effect of preventive interventions on the natural history of NIDDM. C1 GEORGETOWN UNIV,SCH MED,WORTHEN CTR EYE CARE RES,WASHINGTON,DC. UNIV MICHIGAN,DEPT INTERNAL MED,DIV ENDOCRINOL & METAB,ANN ARBOR,MI 48109. PARKE DAVIS INC,ANN ARBOR,MI. MERCK INC,BLUE BELL,PA. BAYER INC,W HAVEN,CT. BATTELLE INC,SEATTLE,WA. WINDWARD SOLUT,REDWOOD CITY,CA. ELI LILLY INC,INDIANAPOLIS,IN. RP Eastman, RC (reprint author), NIDDK,DIV DIABET ENDOCRINOL & METAB DIS,NIH,BLDG 31,ROOM 9A16,31 CTR DR MSC 2560,BETHESDA,MD 20892, USA. NR 32 TC 176 Z9 180 U1 0 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 1997 VL 20 IS 5 BP 725 EP 734 DI 10.2337/diacare.20.5.725 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WW589 UT WOS:A1997WW58900009 PM 9135934 ER PT J AU Eastman, RC Javitt, JC Herman, WH Dasbach, EJ CopleyMerriman, C Maier, W Dong, F Manninen, D Zbrozek, AS Kotsanos, J Garfield, SA Harris, M AF Eastman, RC Javitt, JC Herman, WH Dasbach, EJ CopleyMerriman, C Maier, W Dong, F Manninen, D Zbrozek, AS Kotsanos, J Garfield, SA Harris, M TI Model of Complications of NIDDM .2. Analysis of the health benefits and cost-effectiveness of treating NIDDM with the goal of normoglycemia SO DIABETES CARE LA English DT Article ID DEPENDENT DIABETES-MELLITUS; GLYCEMIC CONTROL; TRIAL; MORTALITY; PROGRESSION; DISEASE; CARE AB OBJECTIVE - To analyze the health benefits and economics of treating NIDDM with the goal of normoglycemia. RESEARCH DESIGN AND METHODS - Incidence-based simulation model of NIDDM was used. Hazard rates for complications were adjusted for glycemia using risk gradients from the Diabetes Control and Complications Trial. Treatment costs were estimated from national survey data and clinical trials. Incremental costs and benefits were expressed in present value dollars (3% discount rate). Life-years were adjusted for quality of life, yielding quality-adjusted life-years (QALYs). RESULTS - Comprehensive treatment of NIDDM that maintains an HbA(1c) value of 7.2% is predicted to reduce the cumulative incidence of blindness, end-stage renal disease, and lower-extremity amputation by 72, 87, and 67%, respectively. Cardiovascular disease risk increased by 3% (no effect of treating glycemia is assumed). Life expectancy increased 1.39 years. The cost of treating hyperglycemia increased by almost twofold, which is partially offset by reductions in the cost of complications. The estimated incremental cost/QALY gained is $16,002. Treatment is more cost-effective for those with longer glycemic exposure (earlier onset of diabetes), minorities, and those with higher HbA(1c) under standard care. CONCLUSIONS - The incremental effectiveness of treating NIDDM with the goal of normoglycemia is estimated to be similar to$16,000/QALY gained, which is in the range of interventions that are generally considered cost-effective. C1 GEORGETOWN UNIV, SCH MED, WORTHEN CTR EYE CARE RES, DEPT OPHTHALMOL, WASHINGTON, DC USA. UNIV MICHIGAN, DEPT INTERNAL MED, DIV ENDOCRINOL & METAB, ANN ARBOR, MI 48109 USA. PARKE DAVIS INC, ANN ARBOR, MI USA. MERCK INC, BLUE BELL, PA USA. BATTELLE INC, SEATTLE, WA USA. BAYER INC, W HAVEN, CT USA. ELI LILLY INC, INDIANAPOLIS, IN USA. RP Eastman, RC (reprint author), NIDDK, DIV DIABET ENDOCRINOL & METAB DIS,NIH,BLDG 31, ROOM 9A16, 31 CTR DR MSC 2560, BETHESDA, MD 20892 USA. NR 46 TC 245 Z9 246 U1 0 U2 3 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 MAY PY 1997 VL 20 IS 5 BP 735 EP 744 DI 10.2337/diacare.20.5.735 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WW589 UT WOS:A1997WW58900010 PM 9135935 ER PT J AU Chen, N Chrambach, A AF Chen, N Chrambach, A TI Isolation of subcellular-sized particles separated by electrophoresis in dilute polymer solution, using commercial electrophoresis apparatus with intermittent scanning of fluorescence SO ELECTROPHORESIS LA English DT Article DE microsome; subcellular-sized particle; particle sieving; dilute polymer medium; preparative electrophoresis; HPGE-1000 apparatus ID PROTEIN AB Resolution cf subcellular-sized particles in electrophoresis employing semidilute polymer solutions as ''sieving media'' improves as the polymer concentration is decreased. Therefore, the previously reported conditions of preparative electrophoresis of microsomes, using concentrated (12%) polyvinylpyrrolidone (PVP) solutions, while solving the problem of non-entrance of large particles into ''sieving media'', do not provide adequate resolving capacity, as exemplified by failure of the microsome preparation used, to resolve in the manner of gels or dilute solutions. The present report provides the conditions under which the HPGE-1000 apparatus can be preparatively applied when the electrophoretic separation is effectively conducted in a dilute polymer solution. The isolation of three microsome components under those conditions constitutes the first application of ''particle sieving'', i.e., a separation due preponderantly to size and shape differences, at a preparative scale. C1 NICHHD,MACROMOL ANAL SECT,LAB CELLULAR & MOL BIOPHYS,NIH,BETHESDA,MD 20892. NR 13 TC 10 Z9 10 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 MAY PY 1997 VL 18 IS 5 BP 781 EP 783 DI 10.1002/elps.1150180520 PG 3 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA XC565 UT WOS:A1997XC56500019 PM 9194606 ER PT J AU Jedlicka, P Mortin, MA Wu, C AF Jedlicka, P Mortin, MA Wu, C TI Multiple functions of Drosophila heat shock transcription factor in vivo SO EMBO JOURNAL LA English DT Article DE development; heat shock; mutant; thermotolerance; transcription ID DNA-BINDING DOMAIN; REGULATORY ELEMENTS; ACTIVATION DOMAIN; GENE-EXPRESSION; DEVELOPMENTAL REGULATION; MOLECULAR-CLONING; FACTOR CONTAINS; YEAST; MELANOGASTER; PROTEIN AB Heat shock transcription factor (HSF) is a transcriptional activator of heat shock protein (hsp) genes in eukaryotes. In order to elucidate the physiological functions of HSF in Drosophila, we have isolated lethal mutations in the hsf gene. Using a conditional allele, we show that HSF has an essential role in the ability of the organism to survive extreme heat stress. In contrast to previous results obtained with yeast HSF, the Drosophila protein is dispensable for general cell growth or viability. However, it is required under normal growth conditions for oogenesis and early larval development. These two developmental functions of Drosophila HSF are genetically separable and appear not to be mediated through the induction of HSPs, implicating a novel action of HSF that may be unrelated to its characteristic function as a stress-responsive transcriptional activator. C1 NEI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. RI Mortin, Mark/B-4251-2008 NR 81 TC 180 Z9 186 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 1 PY 1997 VL 16 IS 9 BP 2452 EP 2462 DI 10.1093/emboj/16.9.2452 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WY677 UT WOS:A1997WY67700027 PM 9171358 ER PT J AU Perfetti, R LeeKwon, W MontroseRafizadeh, C Bernier, M AF Perfetti, R LeeKwon, W MontroseRafizadeh, C Bernier, M TI Overexpression, and activation of the insulin receptor enhances expression of ERCC-1 messenger ribonucleic acid in cultured cells SO ENDOCRINOLOGY LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; TYROSINE KINASE-ACTIVITY; DNA-REPAIR; HUMAN BREAST; GENE ERCC-1; RNA; ASSOCIATION; PROTEINS; COMPLEX; TISSUES AB In this study, a partial hamster complementary DNA encoding ERCC-1, a member of the DNA excision repair gene family, has been cloned. The nucleic acid and amino acid sequences were highly homologous to those of human and mouse ERCC-1. The hamster ERCC-1 gene was expressed as a 1.2-kilobase message in cultured Chinese hamster ovary cells. Northern (RNA) blot analysis revealed that overexpression of the insulin receptor or various growth factor receptor tyrosine kinases in Chinese hamster ovary cells increased ERCC-1 messenger RNA (mRNA) levels. This effect did not occur in cells overexpressing mutated insulin receptors that are known to have impaired kinase-related signaling. Increased ERCC-1 expression correlated with resistance to UV exposure. Fluorescent-activated cell sorter analysis of confluent cell populations indicated no differences in cell cycle distribution. Furthermore, no significant relationship was demonstrated between the relative expression of ERCC-1 mRNA and the rate of glucose utilization. Insulin enhanced the accumulation of ERCC-1 mRNA in serum-deprived cells expressing wild-type insulin receptors. The potential role for activation of the insulin receptor and related growth factor receptors in ERCC-1 gene expression and function remains to be defined. C1 NIA, GERONTOL RES CTR, DIABET SECT, LAB CLIN PHYSIOL, BALTIMORE, MD 21224 USA. OI Bernier, Michel/0000-0002-5948-368X NR 48 TC 6 Z9 6 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 1997 VL 138 IS 5 BP 1829 EP 1835 DI 10.1210/en.138.5.1829 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WU330 UT WOS:A1997WU33000009 PM 9112375 ER PT J AU Fan, GF Goldsmith, PK Collins, R Dunn, CK Krapcho, KJ Rogers, KV Spiegel, AM AF Fan, GF Goldsmith, PK Collins, R Dunn, CK Krapcho, KJ Rogers, KV Spiegel, AM TI N-linked glycosylation of the human Ca2+ receptor is essential for its expression at the cell surface SO ENDOCRINOLOGY LA English DT Article ID CLONING; BINDING; OLIGOSACCHARIDES; PROTEINS; SITES AB The human Ca2+ receptor (hCaR) is a member of the superfamily of G protein-coupled receptors. Its large (similar to 600 residue) amino-terminal extracellular domain contains 9 potential N-linked glycosylation sites. Immunoblot of cell membranes derived from HEK-293 cells, stably transfected with the hCaR, showed two major immunoreactive bands of approximately 150 and 130 kDa, respectively. Complete digestion of the membranes with PN-glycosidase F yielded a single major immunoreactive band of approximately 115 kDa, confirming the presence of N-linked glycosylation. Treatment of these cells with tunicamycin, which blocks N-linked glycosylation, inhibited signal transduction in response to Ca2+. Flow cytometric analysis showed decreased expression of the hCaR on the cell membrane in tunicamycin-treated cells. Immunoblot of tunicamycin-treated cells showed a reduction in the amount of the 150-kDa band and conversion of the 130-kDa band to the presumptively nonglycosylated 115-kDa form. Tunicamycin treatment of cells, transfected with a mutant hCaR complementary DNA containing a nonsense codon at position 599 preceding the 1st transmembrane domain, blocked the secretion of a 95-kDa protein, representing the amino-terminal extracellular domain, into the medium. These results demonstrate that N-linked glycosylation is required for normal expression of the hCaR at the cell surface. C1 NIDDKD, METAB DIS BRANCH, NIH, BETHESDA, MD 20892 USA. NPS PHARMACEUT, SALT LAKE CITY, UT 84108 USA. NR 17 TC 67 Z9 70 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 1997 VL 138 IS 5 BP 1916 EP 1922 DI 10.1210/en.138.5.1916 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WU330 UT WOS:A1997WU33000021 PM 9112387 ER PT J AU Ohlsson, C Swolin, D Sandstedt, J Tornell, J Slootweg, MC AF Ohlsson, C Swolin, D Sandstedt, J Tornell, J Slootweg, MC TI Growth hormone in the regulation of bone formation and bone resorption SO ENDOCRINOLOGY AND METABOLISM LA English DT Article; Proceedings Paper CT 22nd International Symposium on Growth Hormone and Growth Factors in Endocrinology and Metabolism CY OCT 18-19, 1996 CL VIENNA, AUSTRIA ID OSTEOBLAST-LIKE CELLS; ESTROGEN-RECEPTOR GENE; NECROSIS-FACTOR-ALPHA; FACTOR-I; INTERLEUKIN-6 PROMOTER; MINERAL CONTENT; STROMAL CELLS; MICE; 17-BETA-ESTRADIOL; CULTURES C1 NIDDK, DIABET BRANCH, NIH, BETHESDA, MD 20892 USA. GOTHENBURG UNIV, SAHLGRENS HOSP, RES CTR ENDOCRINOL & METAB, S-41345 GOTHENBURG, SWEDEN. FREE UNIV AMSTERDAM HOSP, RES INST ENDOCRINOL REPROD & METAB, AMSTERDAM, NETHERLANDS. FREE UNIV AMSTERDAM HOSP, CENT CHEM LAB, AMSTERDAM, NETHERLANDS. NR 40 TC 0 Z9 0 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1074-939X J9 ENDOCRINOL METAB JI Endocrinol. Metab. PD MAY PY 1997 VL 4 SU B BP 115 EP 118 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XT743 UT WOS:A1997XT74300023 ER PT J AU Paolisso, G Tataranni, PA Bogardus, C Ravussin, E Howard, BV AF Paolisso, G Tataranni, PA Bogardus, C Ravussin, E Howard, BV TI Fasting plasma lipoprotein concentrations and the development of non-insulin dependent diabetes mellitus SO ENDOCRINOLOGY AND METABOLISM LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; CORONARY HEART-DISEASE; PIMA-INDIANS; RISK-FACTORS; RESISTANCE; TRIGLYCERIDE; OBESITY; HYPERTRIGLYCERIDEMIA; HYPERINSULINEMIA; CHOLESTEROL AB The study objective was to evaluate whether fasting plasma lipoprotein concentrations predict the development of non-insulin-dependent diabetes mellitus (NIDDM). Data were analyzed from a longitudinal study of 190 non-diabetic Pima Indians. Glucose tolerance was measured by a 75-g oral glucose tolerance test, and insulin action was measured by a euglycemic hyperinsulinemic (40 mU/m(2) x min) glucose clamp. After a mean follow-up period of 4.0+/-2.4 yr (mean +/- SD), 47 subjects developed NIDDM. Risk factors for NIDDM were estimated by proportional-hazard analysis and risk ratios (RR) with 95% confidence intervals (CI) that were calculated at the 90th and 10th percentiles of the predictive variables. Results of the study indicated that high fasting plasma low-density lipoprotein (LDL) triglyceride concentrations (RR=2.6; 95% CI 1.2-5.8) and low fasting plasma high-density lipoprotein (HDL) cholesterol concentrations (RR=2.6; 95% CI=1.0-6.3) were predictive of the development of NIDDM independent of age, sex, percent body fat and body fat distribution, but did not predict worsening of insulin-mediated glucose uptake. After further adjustment for insulin-mediated glucose uptake, LDL triglyceride and HDL were no longer predictive of the development of NIDDM. The authors conclude that the predictive effect of lipoproteins on NIDDM may be mediated by insulin resistance. C1 MEDLANT RES INST,WASHINGTON,DC 20010. NIDDKD,CLIN DIABET & NUTR SECT,NIH,PHOENIX,AZ 85016. OI Paolisso, Giuseppe/0000-0002-2137-455X NR 43 TC 0 Z9 0 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1074-939X J9 ENDOCRINOL METAB JI Endocrinol. Metab. PD MAY PY 1997 VL 4 IS 3 BP 173 EP 178 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XT154 UT WOS:A1997XT15400005 ER PT J AU Ott, SM Tucci, JR Heaney, RP Marx, SJ AF Ott, SM Tucci, JR Heaney, RP Marx, SJ TI Hypocalciuria and abnormalities in mineral and skeletal homeostasis in patients with celiac sprue without intestinal symptoms SO ENDOCRINOLOGY AND METABOLISM LA English DT Article ID GLUTEN-INDUCED ENTEROPATHY; BODY-COMPOSITION; FREE DIET; DISEASE; DENSITY; OSTEOMALACIA; OSTEOPOROSIS; METABOLISM AB Celiac sprue may be asymptomatic in terms of the gastrointestinal tract and, as a result, may go unrecognized for long periods of time. The objective of this report is to characterize patients who only show signs of abnormalities of mineral and skeletal homeostasis. We present data from six patients seen in academic clinics who eventually were diagnosed with celiac sprue. Serum and urine biochemical tests and bone density were measured. Results showed that the patients had variable initial presentations. Biochemical findings included hypocalciuria, hypocalcemia, low serum 25-OH vitamin D and carotene levels and increased serum parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] levels. Gluten-free diet resulted in clinical improvement. Low urine calcium was a consistent finding in these patients. We conclude that celiac sprue should be considered in patients with osteopenia or hypocalcemia, even in the absence of gastrointestinal signs or symptoms. C1 UNIV WASHINGTON,DIV METAB,SEATTLE,WA 98195. BROWN UNIV,PROVIDENCE,RI 02912. CREIGHTON UNIV,OMAHA,NE 68178. NIDDKD,BETHESDA,MD 20892. NR 30 TC 4 Z9 4 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1074-939X J9 ENDOCRINOL METAB JI Endocrinol. Metab. PD MAY PY 1997 VL 4 IS 3 BP 201 EP 206 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XT154 UT WOS:A1997XT15400009 ER PT J AU Olden, K AF Olden, K TI Thinking big: Four ways to advance environmental health research to answer the needs of public policy SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material RP Olden, K (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 1997 VL 105 IS 5 BP 464 EP 465 DI 10.2307/3433563 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA XF983 UT WOS:A1997XF98300001 PM 9222125 ER PT J AU Bristol, DW Wachsman, JT Greenwell, A AF Bristol, DW Wachsman, JT Greenwell, A TI Comparison of 17 methods of predicting the carcinogenicity of 30 chemicals - Response SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter RP Bristol, DW (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 1997 VL 105 IS 5 BP 467 EP 467 DI 10.2307/3433565 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA XF983 UT WOS:A1997XF98300003 ER PT J AU Buchanan, JR Burka, LT Melnick, RL AF Buchanan, JR Burka, LT Melnick, RL TI Purpose and guidelines for toxicokinetic studies within the National Toxicology Program SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material AB Toxicokinetic studies undertaken within the National Toxicology Program are intended to aid the design of toxicology and carcinogenicity studies, help interpret the results of toxicology and carcinogenicity studies with respect to the relationship between toxic effects and external exposure, and define the parameters of dose, distribution, metabolism, and elimination that can be used in human risk assessment. Descriptions of two study designs presented here represent the possible extremes in approaches to toxicokinetic studies. The comprehensive approach is geared toward the development of physiologically based pharmacokinetic models that relate external exposure to target organ dosimetry and addresses the question: Is the chemical absorbed? How is the chemical metabolized? Where are the chemical and/or metabolites distributed in the body? What are the elimination rate and route of the chemical? What is the effect of dose on absorption, distribution, metabolism, and elimination? The minimal study design is more limited in scope than the comprehensive design and addresses primarily the issues of absorption, distribution, and elimination of the parent chemical. Study protocols for most chemicals lie somewhere between these two extreme approaches. An increased understanding of the relationships between external exposure, target organ dosimetry, and adverse effects should provide greater confidence in making low-dose extrapolations of human risk. This paper focuses on the collection of data from animal toxicokinetic studies. The construction of comparable models to characterize target organ dosimetry in exposed humans would certainly require the use of human parameter values obtained from human tissue samples and volunteers. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP Buchanan, JR (reprint author), MILLERSVILLE UNIV PENNSYLVANIA,DEPT MATH,POB 1002,MILLERSVILLE,PA 17551, USA. NR 4 TC 12 Z9 12 U1 0 U2 1 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 1997 VL 105 IS 5 BP 468 EP 471 DI 10.2307/3433566 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA XF983 UT WOS:A1997XF98300004 PM 9222127 ER PT J AU Swanson, CA Coates, RJ Malone, KE Gammon, MD Schoenberg, JB Brogan, DJ McAdams, M Potischman, N Hoover, RN Brinton, LA AF Swanson, CA Coates, RJ Malone, KE Gammon, MD Schoenberg, JB Brogan, DJ McAdams, M Potischman, N Hoover, RN Brinton, LA TI Alcohol consumption and breast cancer risk among women under age 45 years SO EPIDEMIOLOGY LA English DT Article DE alcohol drinking; breast neoplasms; case control study; age ID SELF-ADMINISTERED QUESTIONNAIRE; BEVERAGE CONSUMPTION; ASSOCIATION; COHORT AB In a population based case control study of women younger than 45 years of age, we obtained a detailed lifetime history of alcohol use to evaluate the effects of drinking during different periods of life in relation to breast cancer risk. This analysis focused on interviews obtained from 1,645 cases and 1,497 controls. Breast cancer risk was not influenced by drinking during the teenage years or early adulthood. Contemporary drinking (that is, average intake during the recent 5-year interval) was directly associated with risk, but the adverse effect of recent drinking was restricted to women who consumed greater than or equal to 14 drinks per week [relative risk (RR) = 1.7; 95% confidence interval (CI) = 1.2-2.5]. The effect of alcohol was most pronounced among women with advanced disease. Compared with nondrinkers, the risk estimate associated with recent consumption of greater than or equal to 14 drinks per week was 2.4 (95% CI = 1.6-3.8) for women with regional/distant disease. Our data add support to the accumulating evidence that alcohol consumption is associated with increased risk of breast cancer and further indicate that alcohol acts at a late stage in breast carcinogenesis. C1 EMORY UNIV,ROLLINS SCH PUBL HLTH,DEPT EPIDEMIOL,ATLANTA,GA 30322. EMORY UNIV,ROLLINS SCH PUBL HLTH,DEPT BIOSTAT,ATLANTA,GA 30322. UNIV WASHINGTON,SCH PUBL HLTH & COMMUNITY MED,DEPT EPIDEMIOL,SEATTLE,WA 98195. UNIV WASHINGTON,SCH PUBL HLTH & COMMUNITY MED,FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98195. COLUMBIA UNIV,SCH PUBL HLTH,DIV EPIDEMIOL,NEW YORK,NY. NEW JERSEY STATE DEPT HLTH,SPECIAL EPIDEMIOL PROGRAM,TRENTON,NJ 08625. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. RP Swanson, CA (reprint author), NCI,NUTR EPIDEMIOL BRANCH,DIV CANC EPIDEMIOL & GENET,NIH,EXECUT PLAZA N,SUITE 443,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 35 TC 66 Z9 66 U1 0 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 1997 VL 8 IS 3 BP 231 EP 237 DI 10.1097/00001648-199705000-00001 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WV745 UT WOS:A1997WV74500005 PM 9115015 ER PT J AU Cohen, PJ AF Cohen, PJ TI 'Off-label' use of prescription drugs: Legal, clinical and policy considerations SO EUROPEAN JOURNAL OF ANAESTHESIOLOGY LA English DT Editorial Material ID DIRECT SPINAL ACTION; ANALGESIA; NARCOTICS; MORPHINE; PAIN RP Cohen, PJ (reprint author), NIDA,MED DEV DIV,NIH,ROCKVILLE,MD, USA. NR 16 TC 12 Z9 13 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0265-0215 J9 EUR J ANAESTH JI Eur. J. Anaesth. PD MAY PY 1997 VL 14 IS 3 BP 231 EP 235 DI 10.1046/j.1365-2346.1997.00112.x PG 5 WC Anesthesiology SC Anesthesiology GA XE750 UT WOS:A1997XE75000001 PM 9202906 ER PT J AU Delphin, C Huang, KP Scotto, C Chapel, A Vincon, M Chambaz, E Garin, J Baudier, J AF Delphin, C Huang, KP Scotto, C Chapel, A Vincon, M Chambaz, E Garin, J Baudier, J TI The in vitro phosphorylation of p53 by calcium-dependent protein kinase C - Characterization of a protein-kinase-C-binding site on p53 SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE p53; protein kinase C; DNA binding ID WILD-TYPE P53; DNA-BINDING; TUMOR-SUPPRESSOR; REGULATORY DOMAIN; SEQUENCE; SUBSTRATE; CALMODULIN; IDENTIFICATION; LOCALIZATION; NEUROGRANIN AB We show that, in vitro, Ca2+-dependent protein kinase C (PKC) phosphorylates recombinant murine p53 protein on several residues contained within a conserved basic region of 25 amino acids, located in the C-terminal part of the protein. Accordingly, synthetic p53-(357-381)-peptide is phosphorylated by PKC at multiple Ser and Thr residues, including Ser360, Thr365, Ser370 and Thr377. We also establish that p53-(357-381)-peptide at micromolar concentrations has the ability to stimulate sequence-specific DNA binding by p53. That stimulation is lost upon phosphorylation by PKC. To further characterise the mechanisms that regulate PKC-dependent phosphorylation of p53-(357-381)-peptide, the phosphorylation of recombinant p53 and p53-(357-381)-peptide by PKC were compared. The results suggest that phosphorylation of full-length p53 on the C-terminal PKC sites is highly dependent on the accessibility of the phosphorylation sites and that a domain on p53 distinct from p53-(357-381)-peptide is involved in binding PKC. Accordingly, we have identified a conserved 27-amino-acid peptide, p53-(320-346)-peptide, within the C-terminal region of p53 and adjacent to residues 357-381 that interacts with PKC in vitro. The interaction between p53-(320-346)-peptide and PKC inhibits PKC autophosphorylation and the phosphorylation of substrates, including p53-(357-381)-peptide, neurogranin and histone H1. Conventional Ca2+-dependent PKC alpha, beta and gamma and the catalytic fragment of PKC (PKM) were nearly equally susceptible to inhibition by p53-(320-346)-peptide. The Ca2+-independent PKC delta was much less sensitive to inhibition. The significance of these findings for understanding the in vivo phosphorylation of p53 by PKC are discussed. C1 BRCE,INSERM,U244,DEPT BIOL MOL & STRUCT,F-38054 GRENOBLE 9,FRANCE. BMCC,INSERM,U309,CEA,DEPT BIOL MOL & STRUCT,GRENOBLE,FRANCE. NICHHD,ENDOCRINOL & REPROD RES BRANCH,NIH,BETHESDA,MD 20892. CEN GRENOBLE,DBMS CP,LAB CHIM PROT,GRENOBLE,FRANCE. RI Baudier, Jacques/O-2183-2016 NR 37 TC 35 Z9 35 U1 0 U2 1 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 MAY 1 PY 1997 VL 245 IS 3 BP 684 EP 692 DI 10.1111/j.1432-1033.1997.t01-1-00684.x PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WY448 UT WOS:A1997WY44800021 PM 9183006 ER PT J AU Newitt, JA Bernstein, HD AF Newitt, JA Bernstein, HD TI The N-domain of the signal recognition particle 54-kDa subunit promotes efficient signal sequence binding SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE signal recognition particle; ribonucleoprotein; signal; GTP; endoplasmic reticulum ID SECRETORY PROTEIN TRANSLOCATION; ENDOPLASMIC-RETICULUM MEMBRANE; METHIONINE-RICH DOMAIN; GTP-BINDING; MICROSOMAL-MEMBRANES; NASCENT PREPROLACTIN; DOCKING PROTEIN; ALPHA-SUBUNIT; RECEPTOR; POLYPEPTIDE AB The signal recognition particle 54-kDa subunit (SRP54) binds to the signal sequences of nascent presecretory and transmembrane proteins. Previous studies have shown that signal sequences bind to the C-terminal methionine-rich domain of the protein (M-domain), but have raised the possibility that either the N-terminal domain (N-domain) or the central guanosine triphosphatase module (GTPase-domain) also contribute to signal-sequence-binding activity. We have generated a series of N-domain and GTPase-domain mutants to investigate this issue further. Mutations in a conserved N-domain motif (ALLEADV) produced significant defects in signal sequence binding that correlate with the severity of the mutation. The magnitude of the defect was independent of the preprotein substrate, which suggested that the mutations do not alter the specificity of signal sequence recognition. The N-domain mutants also showed defects in promoting the translocation of presecretory proteins across the membrane of microsomal vesicles, but these defects appeared to be a direct consequence of the reduction in signal-sequence-binding activity and not separate effects of the mutations. By contrast, mutations in the guanosine triphosphatase consensus sequence had no effect on signal sequence binding, but instead severely impaired protein translocation activity. These results indicate that a principal function of the SRP54 N-domain is to promote efficient signal sequence binding. These data also suggest that the SRP54 GTPase regulates the cycle of signal sequence binding and release, perhaps by modulating the relative orientation of the N- and M-domains. C1 NIDDKD, DEPT BIOCHEM & GENET, NIH, BETHESDA, MD 20982 USA. NR 49 TC 46 Z9 46 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD MAY 1 PY 1997 VL 245 IS 3 BP 720 EP 729 DI 10.1111/j.1432-1033.1997.00720.x PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WY448 UT WOS:A1997WY44800026 PM 9183011 ER PT J AU Esposito, F Cuccovillo, F Vanoni, M Cimino, F Anderson, CW Appella, E Russo, T AF Esposito, F Cuccovillo, F Vanoni, M Cimino, F Anderson, CW Appella, E Russo, T TI Redox-mediated regulation of p21(waf1/cip1) expression involves a post-transcriptional mechanism and activation of the mitogen-activated protein kinase pathway SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE p53; p21(waf1/cip1); mitogen-activated protein kinase; reactive oxygen species ID NIH 3T3 CELLS; P53-INDEPENDENT PATHWAY; SIGNAL-TRANSDUCTION; HUMAN-FIBROBLASTS; MESSENGER-RNA; FREE-RADICALS; INDUCTION; GROWTH; WAF1; P21 AB p21(waf1/cip1) gene expression is induced by DNA damage in cells with wild-type p53 and contributes to the arrest of cell growth. It was demonstrated that under many experimental conditions, including oxidative stress, p21(waf1/cip1) expression can be induced through p53 independent pathways. Since most of these experimental conditions induce the phosphorylation of mitogen-activated protein kinase (MAPK) and thus its activation, we evaluated p21(waf1/cip1) mRNA levels in cells exposed to an oxidative stress, induced by diethylmaleate (Et(2)Mal), and in which the MAPK pathway was blocked. The expression of a dominant-negative mutant of MEK, the MAPK kinase that phosphorylates and activates MAPK, and of a dominant-negative [Asn17]Ras mutant prevented the Et(2)Mal-induced accumulation of p21(waf1/cip1) mRNA. Similarly, the expression of MEK- and of [Asn17]Ras mutants decreased the 12-O-tetradecanoyl-phorbol 13-acetate (TPA)-mediated p21(waf1/cip1) induction. Furthermore, TPA-induced and serum-induced p21(waf1/cip1) mRNA accumulation was blocked by pretreating the cells with the antioxidant compound N-acetylcysteine, suggesting that oxidative stress is involved in these responses. p21(waf1/cip1) mRNA levels reached a maximum within 2 h of adding Et(2)Mal or TPA; however, the rate of transcription from a p21(waf1/cip1)-promoter construct did not increase during this period. In contrast, cells treated with actinomycin D show an increase of p21(waf1/cip1) mRNA stability after Et(2)Mal treatment. This result suggests that the increase in p21(waf1/cip1) mRNA at early times results from post-transcriptional regulatory events. Longer exposure to TPA may activate p21(waf1/cip1) gene transcription through an Sp1-dependent mechanism, while Et(2)Mal treatment gradually inhibits p21(waf1/cip1) gene transcription through oxidative changes that affect Sp1 binding to DNA. C1 UNIV NAPLES,DIPARTIMENTO BIOCHIM & BIOTECNOL MED,I-80131 NAPLES,ITALY. UNIV MILAN,DIPARTIMENTO FISIOL & BIOCHIM GEN,MILAN,ITALY. BROOKHAVEN NATL LAB,DEPT BIOL,UPTON,NY 11973. NCI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. RI Russo, Tommaso/K-1331-2016; Esposito, Franca/K-2024-2016 OI Russo, Tommaso/0000-0003-4426-0106; Esposito, Franca/0000-0001-9340-6875 NR 41 TC 93 Z9 94 U1 0 U2 6 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 MAY 1 PY 1997 VL 245 IS 3 BP 730 EP 737 DI 10.1111/j.1432-1033.1997.00730.x PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WY448 UT WOS:A1997WY44800027 PM 9183012 ER PT J AU Leocani, L Toro, C Manganotti, P Zhuang, P Hallett, M AF Leocani, L Toro, C Manganotti, P Zhuang, P Hallett, M TI Event-related coherence and event-related desynchronization/synchronization in the 10 Hz and 20 Hz EEG during self-paced movements SO EVOKED POTENTIALS-ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE EEG; event-related desynchronization; event-related synchronization; coherence; voluntary movement ID MU-RHYTHM; VOLUNTARY MOVEMENT; PARIETAL RHYTHMS; CORTEX; OSCILLATIONS; SYNCHRONIZATION; IMMOBILITY; POTENTIALS; ATTENTION; BEHAVIOR AB To investigate the activity of cortical regions in the control of movement, we studied event-related desynchronization/synchronization (ERD/ERS), event-related coherence (ERC), and phase coherence in 29-channel EEGs from 9 subjects performing self-paced movements of the right index finger. Movement preparation and execution produced ERD over the sensorimotor areas at 10 Hz and 20 Hz, followed by ERS. ERD corresponded spatiotemporally to an increase in coherence over the frontocentral areas. For both frequency bands, ERD began over the left sensorimotor areas and became bilateral at the time of movement onset. The coherence increase with frontal areas began in the left central areas and became symmetrical after EMG onset. The ERD and coherence increase was longer at 10 Hz than at 20 Hz. Phase coherence at 10 Hz showed a lead of anterior regions to posterior regions throughout the time period, and at 20 Hz showed a tendency toward zero phase delay corresponding with the movement. EEG desynchronization parallels functional coupling over sensorimotor and frontal areas. Event-related coherence and phase coherence findings implicate the frontal lobes in control of movement planning and execution. The involvement of different frequency bands with different timings may represent parallel changes in the cortical network. (C) 1997 Elsevier Science Ltd. C1 NATL INST NEUROL DISORDERS & STROKE,HUMAN MOTOR CONTROL SECT,MED NEUROL BRANCH,NATL INST HLTH,BETHESDA,MD 20892. NR 41 TC 169 Z9 172 U1 1 U2 13 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0168-5597 J9 EVOKED POTENTIAL JI Evoked Potential.-Electroencephalogr. Clin. Neurophysiol. PD MAY PY 1997 VL 104 IS 3 BP 199 EP 206 DI 10.1016/S0168-5597(96)96051-7 PG 8 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA XD246 UT WOS:A1997XD24600002 PM 9186234 ER PT J AU Duffy, CJ Wurtz, RH AF Duffy, CJ Wurtz, RH TI Multiple temporal components of optic flow responses in MST neurons SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE vision; extrastriate; motion; optic flow; cortex ID RABBITS CEREBELLAR FLOCCULUS; MACAQUE MONKEY; SPATIAL-ORGANIZATION; EXPANSION CONTRACTION; VISUAL MESSAGES; ROTATION CELLS; FIELD STIMULI; DORSAL PART; AREA-MT; MOTION AB Neurons in monkey medial superior temporal cortex (MST) respond to optic flow stimuli with early phasic, tonic, and after-phasic response components. In these experiments we characterized each response component to compare its potential contributions to visual motion processing. The early responses begin 60-100 ms after stimulus onset and last between 100 and 250 ms, the tonic responses begin 100-300 ms after stimulus onset and last for as long as the evoking stimulus persists, and the after-responses begin about 60 ms after the stimulus goes off and last for 100-350 ms. A neuron's tonic responses were evoked by specific optic flow stimuli: over two-thirds of the 264 neurons showed tonic responses evoked by two to five stimuli, whereas only 15% responded to either all or none of the stimuli. The tonic responses continued with stimulus presentations as long as 15 s, with their directional preferences being maintained throughout stimulation. However, the tonic response to a given stimulus was seen to change in amplitude when it was presented in random sequence with different sets of other stimuli. Thus, the tonic responses might convey substantial information about optic flour patterns, which continue with prolonged stimulation, but can be modified by the visual context created by other visual motion stimuli, Only about one-third of the 264 neurons had early responses that were selective for specific stimuli. In neurons yielding at least one early response, that neuron was most often activated by all the visual motion stimuli. After-rsponses occurred in only half the neurons, but they were more often specifically related to particular optic flow stimuli, regardless of whether those stimuli had evoked tonic excitatory or tonic inhibitory responses. The presence of early and after-responses complicates the interpretation of activity evoked when one stimulus immediately follows another. However, under those conditions, early responses and after-responses might contribute to signaling changes in the ongoing pattern of optic flow. We conclude that several components of MST responses should be recognized and that they potentially play different roles in the cortical analysis of optic flow, Tonic responses show the greatest specificity for particular optic flow stimuli, and possess characteristics which make them suitable neuronal participants in self-movement perception. C1 UNIV ROCHESTER, MED CTR, DEPT NEUROBIOL & ANAT, ROCHESTER, NY 14642 USA. UNIV ROCHESTER, MED CTR, DEPT OPHTHALMOL, ROCHESTER, NY 14642 USA. UNIV ROCHESTER, MED CTR, DEPT BRAIN & COGNIT SCI, ROCHESTER, NY 14642 USA. UNIV ROCHESTER, MED CTR, CTR VISUAL SCI, ROCHESTER, NY 14642 USA. NEI, NIH, SENSORIMOTOR RES LAB, BETHESDA, MD 20892 USA. RP Duffy, CJ (reprint author), UNIV ROCHESTER, MED CTR, DEPT NEUROL, BOX 673, ROCHESTER, NY 14642 USA. NR 33 TC 37 Z9 37 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD MAY PY 1997 VL 114 IS 3 BP 472 EP 482 DI 10.1007/PL00005656 PG 11 WC Neurosciences SC Neurosciences & Neurology GA XA986 UT WOS:A1997XA98600008 PM 9187283 ER PT J AU Bettelheim, FA Churchill, AC Siew, EL Tumminia, SJ Russell, P AF Bettelheim, FA Churchill, AC Siew, EL Tumminia, SJ Russell, P TI Light scattering and morphology of cataract formation in transgenic mice containing the HIV-1 protease linked to the lens alpha A-crystallin promoter SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE birefringence; cataract; HIV-1 protease; mouse lens; polarized light scattering; protein aggregates; scanning electron microscopy ID OPTICAL ANISOTROPY; FLUCTUATION THEORY; EYE AB Two constructs of transgenic mice, TG(61) and TG(72), containing the HIV-1 protease linked to the lens alpha A-crystallin promoter develop cataract. The TG(61) construct develop cataract in utero. while the TG(72) construct exhibit frank opacities on the 24th day (homozygotes) and 26th day (hemizygotes) post natum. Polarized light scattering measurements were performed on cortical and nuclear sections of TG(72) lenses from day 19 to day 26 as a function of scattering angle. The parallel components of the scattered light intensity increase gradually during opacification, the perpendicular components show very low values from day 19 to day 22 after which they increase exponentially. Analysis of the scattered light intensities yielded parameters describing the size of the protein aggregates. the size of the domains exhibiting optical anisotropy/birefringence, the difference in refractive index between (a) the protein aggregates and their surroundings and (b) the birefringent units and their surroundings. The last parameter accounts for the major portion of the increase in lens turbidity. The TG(72) construct shows normal lens development on day 16. By day 21 the posterior cortex shows some disintegration, while the lens is still clear. By day 26 the lens nucleus migrates toward the posterior pole and there is a major alteration in the cortical fibers. Scanning electron microscopic studies reveal normal fiber cell organizations in control animals. In the TG(72) construct the fiber cells are well organized at 16 days after birth but already develop some slight separation in the posterior cortical part of the lens. By post-natal day 21, the nucleus and the anterior cortex still exhibit well aligned fiber cell organization, but the posterior cortex shows disalignment. By day 26 in the TG(72) construct, all areas of the lens show complete disintegration of the fiber cells and amorphous masses are present throughout. The light scattering parameters describing changes on the nanometer scale can be correlated with the changes in lens morphology during cataractogenesis that occur on the micrometer scale. In comparison, the light and scanning electron microscopic examinations of the postnatal TG(61) construct show that the lens is severely disrupted and contains completely disintegrated fiber cell remnants at an early age. (C) 1997 Academic Press Limited. C1 ADELPHI UNIV, DEPT BIOL, GARDEN CITY, NY 11530 USA. SUNY, HVCC, DEPT CHEM, TROY, NY 12180 USA. NEI, LAB OCULAR DIS, NIH, BETHESDA, MD 20892 USA. RP Bettelheim, FA (reprint author), ADELPHI UNIV, DEPT CHEM, GARDEN CITY, NY 11530 USA. FU NEI NIH HHS [EY-02571] NR 25 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD MAY PY 1997 VL 64 IS 5 BP 667 EP 674 DI 10.1006/exer.1996.0233 PG 8 WC Ophthalmology SC Ophthalmology GA XD248 UT WOS:A1997XD24800002 PM 9245895 ER PT J AU Shefer, VI Talan, MI AF Shefer, VI Talan, MI TI Change in heat loss as a part of adaptation to repeated cold exposures in adult and aged male C57BL/6J mice SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE aging; thermoregulation; mice; heat production; colonic temperature; acclimation; heat conservation ID STRESS; ACCLIMATION; RESPONSES AB Previous studies have shown that adult mice increase cold-induced heat production as a result of repeated exposures to cold, but that aged mice do not. The objective of the present study was to investigate changes in heat loss during repeated cold exposures in adult and aged C57BL/6J mice. Mice were partially restrained for three hours at 6 degrees C, three times at one-week intervals. Dry heat loss was inferred from measurements of differential temperature between the incoming and outgoing air in the experimental chamber. During the first cold exposure, aged mice showed less heat loss (both total and adjusted for body temperature) than adult animals, suggesting greater peripheral vasoconstriction in aged mice. With repeated cold exposures, both age groups showed increased heat loss, but the aged mice showed greater increase of heat loss, so that by the third cold stress test, no significant differences in heat loss between adult and aged mice were observed. The increase of heat loss after repeated cold exposures in aged mice might reflect a lesser peripheral vasoconstriction, serving to reduce the possibility of tissue necrosis in the cold. (C) 1997 Elsevier Science Inc. C1 NIA, GERONTOL RES CTR, BEHAV SCI LAB, NIH, BALTIMORE, MD 21224 USA. NR 20 TC 4 Z9 4 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD MAY-JUN PY 1997 VL 32 IS 3 BP 325 EP 332 DI 10.1016/S0531-5565(96)00131-3 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA XA774 UT WOS:A1997XA77400008 PM 9193900 ER PT J AU Soubes, SC Wellems, TE Miller, LH AF Soubes, SC Wellems, TE Miller, LH TI Plasmodium falciparum: A high proportion of parasites from a population of the Dd2 strain are able to invade erythrocytes by an alternative pathway SO EXPERIMENTAL PARASITOLOGY LA English DT Article ID ANTIGENIC VARIATION; MALARIA PARASITES; GENE-EXPRESSION; PHASE VARIATION; PROTEIN-II; INVASION; RECEPTOR; PHENOTYPES C1 NIAID,LPD,NIH,BETHESDA,MD 20892. NR 20 TC 19 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 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD MAY PY 1997 VL 86 IS 1 BP 79 EP 83 DI 10.1006/expr.1997.4153 PG 5 WC Parasitology SC Parasitology GA WY119 UT WOS:A1997WY11900009 PM 9149243 ER PT J AU Ambs, S Hussain, SP Harris, CC AF Ambs, S Hussain, SP Harris, CC TI Interactive effects of nitric oxide and the p53 tumor suppressor gene in carcinogenesis and tumor progression SO FASEB JOURNAL LA English DT Review DE apoptosis; mutagenesis; DNA damage; molecular epidemiology ID ENDOTHELIAL GROWTH-FACTOR; TATA-BINDING PROTEIN; C-TERMINAL DOMAIN; DNA-REPLICATION; IN-VITRO; TRANSCRIPTIONAL ACTIVATION; SYNTHASE ACTIVITY; WILD-TYPE; APOPTOSIS; DAMAGE AB The tumor suppressor gene product p53 plays an important role in the cellular response to DNA damage, DNA damage can lead to p53-mediated growth arrest and apoptosis, High concentrations of nitric oxide (NO) and NO metabolites such as peroxynitrite and NO2 cause DNA damage and have been shown to be mutagenic. Furthermore, NO induces p53 accumulation and, as part of a feedback loop, p53 mediates transcriptional transrepression of inducible nitric oxide synthase. Recent studies have shown increased expression and activity of nitric oxide synthase isoforms in human cancer. NO has both genotoxic and angiogenic properties, so that increased NO production may select mutant p53 cells and contribute to human carcinogenesis and tumor progression. C1 NCI,HUMAN CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. NR 89 TC 173 Z9 180 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY PY 1997 VL 11 IS 6 BP 443 EP 448 PG 6 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA XE404 UT WOS:A1997XE40400006 PM 9194524 ER PT J AU Malinda, KM Goldstein, AL Kleinman, HK AF Malinda, KM Goldstein, AL Kleinman, HK TI Thymosin beta(4) stimulates directional migration of human umbilical vein endothelial cells SO FASEB JOURNAL LA English DT Article DE migration; angiogenesis; human umbilical vein endothelial cells; T beta(4) ID DEOXYNUCLEOTIDYL TRANSFERASE-ACTIVITY; DIFFERENTIAL EXPRESSION; BASEMENT-MEMBRANE; LIVING CELLS; BETA-4 GENE; IN-VITRO; ACTIN; ANGIOGENESIS; LAMININ; PEPTIDE AB Thymosin beta(4) (T beta(4)) is a 4.9 kDa polypeptide that interacts with G-actin and is thought to be an important mediator in cell proliferation, migration, and differentiation. T beta(4) has been identified as a factor involved in the differentiation of human umbilical vein endothelial cells (HUVECs) cultured on Matrigel, Here we have used various in vitro and in vivo migration assays to demonstrate the role of T beta(4) in endothelial cell migration, Our results demonstrate that T beta(4) acts as a chemoattractant for endothelial cells, stimulating the migration of HUVECs in Boyden chambers four- to sixfold over that observed with media alone, Of the primary cell types tested, only human coronary artery cells responded to T beta(4) treatment, suggesting that the migration activity of T beta(4) was endothelial cell-specific, T beta(4) significantly accelerated the rate of migration into the scratch wounded area of a HUVEC monolayer, T beta(4) treatment also increased the production of matrix metalloproteinases that may degrade the basement membrane during angiogenesis, Additional experiments using subcutaneously implanted Matrigel showed that T beta(4) stimulated cell migration in vivo. These results provide the first direct evidence that T beta(4) has chemoattractive activity and promotes angiogenesis by stimulating the migration of endothelial cells. C1 NIDR,NIH,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,SCH MED & HLTH SCI,DEPT BIOCHEM & MOL BIOL,WASHINGTON,DC 20037. NR 39 TC 163 Z9 176 U1 2 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY PY 1997 VL 11 IS 6 BP 474 EP 481 PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA XE404 UT WOS:A1997XE40400010 PM 9194528 ER PT J AU Ho, MN Delgado, CH Owens, GA Steller, MA AF Ho, MN Delgado, CH Owens, GA Steller, MA TI Insulin-like growth factor-II participates in the biphasic effect of a gonadotropin-releasing hormone agonist on ovarian cancer cell growth SO FERTILITY AND STERILITY LA English DT Article DE IGF-II; tryptorelin; biphasic; ovarian cancer ID RECEPTOR; EXPRESSION; BINDING; INHIBITION; ANALOGS; TUMORS; PROLIFERATION; ANTAGONISTS; CARCINOMA; AUTOCRINE AB Objective: To examine the involvement of insulin-like growth factors (IGFs) in growth regulation of an ovarian cancer cell line and to investigate whether the GnRH agonist tryptorelin might influence a potential autocrine or paracrine loop involving IGFs. Design: In vitro, prospective, randomized controlled study. Setting: In vitro experiments at the Section of Gynecologic Oncology, Surgery Branch, National Cancer Institute. Patient(s): None. Human ovarian adenocarcinoma cell line IGROV-1. Intervention(s): The proliferative effect of tryptorelin on IGROV-1 cells was analyzed by using the MTT (93-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide) colorimetric assay. The ribonuclease protection assay was used to investigate whether an autocrine pathway involving IGF-I or IGF-II might participate in the growth of these cells. The expression of GnRH receptor was assessed by the I-125-GnRH binding assay. Main Outcome Measure(s): Changes in cell growth and expression of IGF-I and IGF-II messenger RNA (mRNA). Result(s): Tryptorelin exhibited a bimodal, dose- and time-dependent effect on IGROV-1 cells when compared with untreated control cells: Cellular proliferation was enhanced during the first 24 hours of exposure, but longer incubations resulted in growth inhibition. The mitogenic effect of tryptorelin was inhibited when cells were co-incubated with either IGF binding protein-5 (IGFBP-5) or anti-IGF-II antibody, which can both bind to IGF-II and neutralize it. Insulinlike growth factor-I mRNA was not detected in IGROV-1 cells. However, IGF-II transcripts were detected after incubation with tryptorelin for 12 hours, but thereafter, no mRNA was observed, even after prolonged exposure. Binding analysis revealed a specific, high-affinity GnRH binding site. Conclusion(s): These data suggest that tryptorelin exerts a bimodal growth effect on ovarian cancer cells by a mechanism involving the autocrine production of IGF-II. The effect of tryptorelin on IGF-II gene transcription in these ovarian cancer cells appears to mirror the desensitizing effects of prolonged GnRH exposure on pituitary gonadotropin production. (C) 1997 by American Society for Reproductive Medicine. C1 NCI,SURG BRANCH,GYNECOL ONCOL SECT,BETHESDA,MD 20892. NR 25 TC 23 Z9 23 U1 0 U2 0 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAY PY 1997 VL 67 IS 5 BP 870 EP 876 DI 10.1016/S0015-0282(97)81399-4 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA WV719 UT WOS:A1997WV71900012 PM 9130892 ER PT J AU Page, NP Singh, DV Farland, W Goodman, JI Conolly, RB Andersen, ME Clewell, HJ Frederick, CB Yamasaki, H Lucier, G AF Page, NP Singh, DV Farland, W Goodman, JI Conolly, RB Andersen, ME Clewell, HJ Frederick, CB Yamasaki, H Lucier, G TI Implementation of EPA revised cancer assessment guidelines: Incorporation of mechanistic and pharmacokinetic data SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Editorial Material ID REGENERATIVE CELL-PROLIFERATION; FEMALE B6C3F1 MICE; MOUSE-LIVER TUMORS; DRINKING-WATER; RISK ASSESSMENTS; AD-LIBITUM; F344 RATS; CORN-OIL; CHLOROFORM; TRICHLOROETHYLENE AB A workshop entitled ''Implementation of EPA Revised Cancer Assessment Guidelines: Incorporation of Mechanistic and Pharmacokinetic Data'' was held in Anaheim, California, in 1996 at the 35th Annual Meeting of the Society of Toxicology (SOT), This workshop was jointly sponsored by the Carcinogenesis, Risk; Assessment, and Veterinary Specialty Sections of the SOT, The thrust of the workshop was to discuss the scientific basis for the revisions to the EPA Guidelines for cancer assessment and EPA's plans for their implementation, This is the first revision to the original EPA guidelines which have been in use by EPA since 1986. The principal revisions are intended to provide a framework for an increased ability to incorporate biological data into the risk assessment process. Two cases were presented, for chloroform and trichloroethylene, that demonstrated the use of the revised guidelines for specific cancer risk assessments. Using these new guidelines, nonlinear margin of exposure analyses were proposed for these chemicals instead of the linearized multistage model previously used by the EPA as the default method. The workshop participants generally applauded the planned revisions to the EPA guidelines, For the most part, they considered that the revised guidelines represented a positive step which should allow for and encourage the use of biological information in the conduct of cancer risk assessments. Several participants cautioned however that the major problem with cancer risk assessments would continue to be the inadequacy of available data on which to conduct more scientific risk assessments. (C) 1997 Society of Toxicology. C1 US EPA,NCEA DC,WASHINGTON,DC 20460. MICHIGAN STATE UNIV,E LANSING,MI 48824. CHEM IND INST TOXICOL,RES TRIANGLE PK,NC 27709. ICF KAISER ENGINEERS,RES TRIANGLE PK,NC 27709. ICF KAISER ENGINEERS,RUSTON,LA 71270. ROHM & HAAS CO,SPRING HOUSE,PA 19477. INT AGCY RES CANC,F-69372 LYON 08,FRANCE. NIEHS,RES TRIANGLE PK,NC 27709. RP Page, NP (reprint author), TAXACHEM INT,POB 10547,GAITHERSBURG,MD 20849, USA. OI Andersen, Melvin/0000-0002-3894-4811 NR 55 TC 15 Z9 15 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 MAY PY 1997 VL 37 IS 1 BP 16 EP 36 DI 10.1006/faat.1997.2305 PG 21 WC Toxicology SC Toxicology GA XE401 UT WOS:A1997XE40100002 PM 9193920 ER PT J AU Liu, L Goldstein, AM Tucker, MA Brill, H Gruis, NA Hogg, D Lassam, NJ AF Liu, L Goldstein, AM Tucker, MA Brill, H Gruis, NA Hogg, D Lassam, NJ TI Affected members of melanoma-prone families with linkage to 9p21 but lacking mutations in CDKN2A do not harbor mutations in the coding regions of either CDKN2B or p19(ARF) SO GENES CHROMOSOMES & CANCER LA English DT Article ID GENE; P16; KINDREDS; TRANSCRIPT; PROTEINS; LOCUS AB Mutations in the gene encoding the cell cycle inhibitor CDKN2A have been identified in some melanoma kindreds linked to 9p21. However, many such families show no evidence of mutations in the coding regions of CDKN2A. In this study, we examined whether two other potential tumor suppressors, CDKN2B and p19(ARF), which also map within the 9p21 region, play a role in the development of familial melanoma. We found no mutations in the coding regions of either gene in melanoma-prone families with evidence of linkage to 9p21. We conclude either that another melanoma susceptibility gene exists within this chromosomal area or that mutations in noncoding regions of CDKN2A, CDKN2B, or p19(ARF) predispose to melanoma. (C) 1997 Wiley-Liss, Inc. C1 UNIV TORONTO,DEPT MED BIOPHYS,TORONTO,ON M5S 1A8,CANADA. UNIV TORONTO,DEPT MED,TORONTO,ON M5S 1A8,CANADA. NCI,GENET EPIDEMIOL BRANCH,BETHESDA,MD. LEIDEN UNIV,MGC DEPT HUMAN GENET,LEIDEN,NETHERLANDS. RI Tucker, Margaret/B-4297-2015; OI Gruis, Nelleke/0000-0002-5210-9150 NR 23 TC 35 Z9 35 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD MAY PY 1997 VL 19 IS 1 BP 52 EP 54 DI 10.1002/(SICI)1098-2264(199705)19:1<52::AID-GCC8>3.3.CO;2-S PG 3 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA WV910 UT WOS:A1997WV91000008 PM 9135995 ER PT J AU Wolffe, AP Wong, JM Pruss, D AF Wolffe, AP Wong, JM Pruss, D TI Activators and repressors: Making use of chromatin to regulate transcription SO GENES TO CELLS LA English DT Review ID YEAST SWI/SNF COMPLEX; TATA-BINDING PROTEIN; RNA-POLYMERASE-II; SACCHAROMYCES-CEREVISIAE; HISTONE ACETYLATION; NEGATIVE REGULATOR; NUCLEOSOMAL DNA; MULTISUBUNIT COMPLEX; GLUCOSE REPRESSION; GENE-PRODUCTS AB Metazoans and yeast use enzymes that modulate histone acetylation and nucleosomal integrity in order to regulate transcription. Repressor complexes deacetylate histones and stabilize nucleosomes. Activator complexes acetylate histones and disrupt nucleosomes. Variation in chromatin structure makes a major contribution to gene regulation. Here we discuss the enzymatic complexes and molecular machines that make use of chromatin to control transcription. C1 NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892. NR 103 TC 65 Z9 66 U1 1 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 1356-9597 J9 GENES CELLS JI Genes Cells PD MAY PY 1997 VL 2 IS 5 BP 291 EP 302 DI 10.1046/j.1365-2443.1997.1260323.x PG 12 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA XL828 UT WOS:A1997XL82800001 PM 9280341 ER PT J AU Voloshin, ON CameriniOtero, RD AF Voloshin, ON CameriniOtero, RD TI The duplex DNA is very underwound in the three-stranded RecA protein-mediated synaptic complex SO GENES TO CELLS LA English DT Article ID ESCHERICHIA-COLI; HOMOLOGOUS RECOMBINATION; POTASSIUM-PERMANGANATE; DIETHYL PYROCARBONATE; SUPERHELICAL STRESS; TELOMERIC SEQUENCE; 3-STRANDED DNA; HELICAL REPEAT; LOW PH; B-DNA AB Background: The RecA protein is a central player in bacterial homologous recombination. It promotes two key events: the search for homology between two DNA molecules and the subsequent formation of the synaptic complex composed of RecA and three DNA strands (two from one duplex and one single strand). In spite of numerous studies, the architecture of the synaptic complex is still far from clear. Results: We have exploited two approaches to study the structure of Escherichia coli RecA protein-mediated DNA synapsis: chemical modification with potassium permanganate and treatment of synaptic complexes of different lengths with topoisomerase I. The linking number difference values, obtained after separation of the individual sets of topoisomers in an agarose gel, were used to determine the number of bases per helical turn. We were able to show that the topology of the three-stranded complexes containing RecA is quite different from that expected for deproteinized D-loops. The original duplex in the synaptic complex is unwound, but not necessarily unpaired, to a structure topologically equivalent to DNA with approximately 27 bp per turn. Despite the fact that the patterns of reactivity towards potassium permanganate cannot be interpreted unambiguously, the results of chemical footprinting can be explained in terms of a synaptic complex as an extended and unwound three-stranded helical structure. Conclusions: This work provides the first quantitative topological parameters for the RecA protein-mediated three-stranded synaptic complex. Furthermore, the structure of synaptic complexes is different from that of a simple D-loop. C1 NIDDKD,GENET & BIOCHEM BRANCH,NIH,BETHESDA,MD 20892. NR 52 TC 17 Z9 18 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 1356-9597 J9 GENES CELLS JI Genes Cells PD MAY PY 1997 VL 2 IS 5 BP 303 EP 314 DI 10.1046/j.1365-2443.1997.1240322.x PG 12 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA XL828 UT WOS:A1997XL82800002 PM 9280342 ER PT J AU Koonin, EV AF Koonin, EV TI Big time for small genomes SO GENOME RESEARCH LA English DT Review RP Koonin, EV (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20892, USA. NR 0 TC 16 Z9 16 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 MAY PY 1997 VL 7 IS 5 BP 418 EP 421 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA WX931 UT WOS:A1997WX93100003 PM 9149938 ER PT J AU Schuler, GD AF Schuler, GD TI Sequence mapping by electronic PCR SO GENOME RESEARCH LA English DT Article ID HUMAN GENOME; MAP AB The highly specific and sensitive PCR provides the basis for sequence-tagged sites (STSs), unique landmarks that have been used widely in the construction of genetic and physical maps of the human genome. Electronic PCR (e-PCR) refers to the process of recovering these unique sites in DNA sequences by searching for subsequences that closely match the PCR primers and have the correct order, orientation, and spacing that they could plausibly prime the amplification of a PCR product of the correct molecular weight. A software tool was developed to provide an efficient implementation of this search strategy and allow the sort of en masse searching that is required for modern genome analysis. Some sample searches were performed to demonstrate a number of factors that can affect the likelihood of obtaining a match. Analysis of one large sequence database record revealed the presence of several microsatellite and gene-based markers and allowed the exact base-pair distances among them to be calculated. This example provides a demonstration of how e-PCR can be used to integrate the growing body of genomic sequence data with existing maps, reveal relationships among markers that existed previously on different maps, and correlate genetic distances with physical distances. RP Schuler, GD (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20984, USA. NR 16 TC 211 Z9 231 U1 1 U2 8 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 GENOME RES JI Genome Res. PD MAY PY 1997 VL 7 IS 5 BP 541 EP 550 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA WX931 UT WOS:A1997WX93100014 PM 9149949 ER PT J AU Chung, WK Zheng, M Chua, M Kershaw, E PowerKehoe, L Tsuji, M WuPeng, XS Williams, J Chua, SC Leibel, RL AF Chung, WK Zheng, M Chua, M Kershaw, E PowerKehoe, L Tsuji, M WuPeng, XS Williams, J Chua, SC Leibel, RL TI Genetic modifiers of Lepr(fa) associated with variability in insulin production and susceptibility to NIDDM SO GENOMICS LA English DT Article ID DEPENDENT DIABETES-MELLITUS; IMMUNOPEROXIDASE TECHNIQUES; PEROXIDASE COMPLEX; GLUCOSE-TOLERANCE; RAT FATTY; MOUSE; OBESITY; PREVALENCE; LOCUS; SEX AB In an attempt to identify the genetic basis for susceptibility to non-insulin-dependent diabetes mellitus within the context of obesity, me generated 401 genetically obese Lepr(fa)/Lepr(fa) F2 WKY13M intercross rats that demonstrated wide variation in multiple phenotypic measures related to diabetes, including plasma glucose concentration, percentage of glycosylated hemoglobin, plasma insulin concentration, and pancreatic islet morphology. Using selective genotyping genome scanning approaches, me have identified three quantitative trait loci (QTLs) on Chr. 1 (LOD 7.1 for pancreatic morpholology), Chr. 12 (LOD 5.1 for body mass index and LOD 3.4 for plasma glucose concentration), and Chr. 16 (P < 0.001 for genotype effect on plasma glucose concentration). The obese F2 progeny demonstrated sexual dimorphism for these traits, with increased diabetes susceptibility in the males appearing at approximately 6 weeks of age, as sexual maturation occurred. For each of the QTLs, the linked phenotypes demonstrated sexual dimorphism (more severe affection in males). The QTL on Chr. 1 maps to a region vicinal to that previously linked to adiposity in studies of diabetes susceptibility in the nonobese Goto-Kakizaki rat, which is genetically closely related to the Wistar counterstrain we employed. Several candidate genes, including tubby (tub), multigenic obesity I (Mob1), adult obesity and diabetes (Ad), and insulin-like growth factor-2 (Igf2), map to murine regions homologous to the QTL region identified on rat Chr. 1. (C) 1997 Academic Press. C1 ROCKEFELLER UNIV,HUMAN BEHAV & METAB LAB,NEW YORK,NY 10021. VASSAR COLL,DEPT BIOL,ANIM MODEL CORE LAB,NIH,POUGHKEEPSIE,NY 12601. RI Kershaw, Erin/G-9587-2013 FU NIDDK NIH HHS [DK47473, DK26687, DK52431] NR 60 TC 55 Z9 55 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 MAY 1 PY 1997 VL 41 IS 3 BP 332 EP 344 DI 10.1006/geno.1997.4672 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WX153 UT WOS:A1997WX15300006 PM 9169130 ER PT J AU McGuire, RE Daiger, SP Green, ED AF McGuire, RE Daiger, SP Green, ED TI Localization and characterization of the human ADP-ribosylation factor 5 (ARF5) gene SO GENOMICS LA English DT Article ID NUCLEOTIDE-BINDING-PROTEINS; CHOLERA-TOXIN; DROSOPHILA-MELANOGASTER; REGULATORY COMPONENT; ADENYLATE-CYCLASE; MESSENGER-RNA; EXPRESSION; PSEUDOGENE; ACTIVATORS AB ADP-ribosylation factor 5 (ARF5) is a member of the ARF gene family. The ARF proteins stimulate the in vitro ADP-ribosyltransferase activity of cholera toxin and appear to play a role in vesicular trafficking in vivo. We have mapped ARF5, one of the six known mammalian ARF genes, to a well-defined yeast artificial chromosome contig on human chromosome 7q31.3. In addition, we have isolated and sequenced an similar to 3.2-kb genomic segment that contains the entire ARF5 coding region, revealing the complete intron-exon structure of the gene. With six coding exons and five introns, the genomic structure of ARF5 is unique among the mammalian ARF genes and provides insight about the evolutionary history of this ancient gene family. (C) 1997 Academic Press. C1 NATL HUMAN GENOME RES INST,GENOME TECHNOL BRANCH,NIH,BETHESDA,MD 20892. UNIV TEXAS,HLTH SCI CTR,CTR HUMAN GENET,HOUSTON,TX 77225. UNIV TEXAS,HLTH SCI CTR,DEPT OPHTHALMOL,HOUSTON,TX 77225. FU NEI NIH HHS [R01 EY007142, EY07142, EY07024] NR 20 TC 6 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 MAY 1 PY 1997 VL 41 IS 3 BP 481 EP 484 DI 10.1006/geno.1997.4689 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WX153 UT WOS:A1997WX15300027 PM 9169151 ER PT J AU Becker, KG Nagle, JW Canning, RD Dehejia, AM Polymeropoulos, MH Gado, AM Biddison, WE Drew, PD AF Becker, KG Nagle, JW Canning, RD Dehejia, AM Polymeropoulos, MH Gado, AM Biddison, WE Drew, PD TI Molecular cloning and mapping of a novel human KRAB domain-containing C2H2-type zinc finger to chromosome 7q36.1 SO GENOMICS LA English DT Article ID TRANSCRIPTIONAL REPRESSION; GENE; MAPS C1 NINCDS,NEUROIMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NINCDS,NEUROGENET LAB,NIH,BETHESDA,MD 20892. NIH,GENE MAPPING UNIT,LAB GENET DIS RES,NCHGR,BETHESDA,MD 20892. OI Becker, Kevin/0000-0002-6794-6656 NR 13 TC 5 Z9 6 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 MAY 1 PY 1997 VL 41 IS 3 BP 502 EP 504 DI 10.1006/geno.1997.4678 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WX153 UT WOS:A1997WX15300033 PM 9169157 ER PT J AU Hall, KL Teneriello, MG Taylor, RR Lemon, S Ebina, M Linnoila, RI Norris, H Park, RC Birrer, MJ AF Hall, KL Teneriello, MG Taylor, RR Lemon, S Ebina, M Linnoila, RI Norris, H Park, RC Birrer, MJ TI Analysis of Ki-ras, p53, and MDM2 genes in uterine leiomyomas and leiomyosarcomas SO GYNECOLOGIC ONCOLOGY LA English DT Article ID TUMOR-SUPPRESSOR GENE; SMOOTH-MUSCLE TUMORS; CELL LUNG-CANCER; MUTATIONS; OVEREXPRESSION; SARCOMAS; PROTEIN AB Uterine sarcomas are unusual neoplasms of the female genital tract whose molecular etiology is largely unknown. We examined 20 leiomyomas as well as 23 uterine leiomyosarcomas for the presence of mutations in the Ki-ras and p53 genes, and overexpression of the MDM2 gene. Codons 12, 13, and 61 from the Ki-ras gene were characterized for the presence of mutations by restriction enzyme polymorphisms using mismatched primers and nucleic acid sequencing as appropriate, Activated Ki-ras genes were identified in 3/20 leiomyomas and 0/23 leiomyosarcomas. The p53 gene was analyzed by SSCP, nucleic acid sequencing, and immunohistochemical staining, None of 20 leiomyomas and 6/23 leiomyosarcomas exhibited p53 abnormalities. The SSCP/sequencing results did not consistently correlate with the IHC staining. MDM2 overexpression occurred in 0/20 leiomyomas and 3/23 sarcomas. Clinical correlation suggested that tumors with p53 mutations have a higher histologic grade or stage at presentation, We conclude that leiomyomas and leiomyosarcomas have different patterns of molecular alterations and are separate biologic entities. In addition, p53 and MDM2 overexpression may play a role in the development of a subset of leiomyosarcomas. (C) 1997 Academic Press. C1 NCI, BIOMARKERS & PREVENT RES BRANCH, DIV CLIN SCI, ROCKVILLE, MD 20850 USA. BROOKE ARMY MED CTR, DEPT OBSTET & GYNECOL GYNECOL ONCOL, FT SAM HOUSTON, TX 78234 USA. NATL NAVAL MED CTR, BETHESDA, MD 20889 USA. WALTER REED ARMY MED CTR, WASHINGTON, DC 20307 USA. NR 20 TC 56 Z9 58 U1 0 U2 4 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 MAY PY 1997 VL 65 IS 2 BP 330 EP 335 DI 10.1006/gyno.1997.4653 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA WZ671 UT WOS:A1997WZ67100024 PM 9159347 ER PT J AU Hamrick, PE AF Hamrick, PE TI A computerized radioactive material inventory system using a commercially available database program SO HEALTH PHYSICS LA English DT Article DE operational topic; radionuclide; computers; safety standards AB An accurate and current radioactive materials inventory is essential for efficient control and use of radioactive material. In order to facilitate data entry, a computerized radioactive material inventory procedure has been developed using a commercially available database program, This system allows inventory records to be entered and updated quickly and efficiently with desired reports generated, without needing extensive computer training or programming skills. C1 NIEHS, RES TRIANGLE PK, NC 27709 USA. DIGITAL EQUIPMENT CORP, NORTHBOROUGH, MA 01532 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD MAY PY 1997 VL 72 IS 5 BP 788 EP 794 DI 10.1097/00004032-199705000-00017 PG 7 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 WT523 UT WOS:A1997WT52300018 PM 9106723 ER PT J AU Kachar, B Battaglia, A Fex, J AF Kachar, B Battaglia, A Fex, J TI Compartmentalized vesicular traffic around the hair cell cuticular plate SO HEARING RESEARCH LA English DT Article DE hair cell; cuticular plate; vesicular traffic; apical membrane recycling; bullfrog macula ID MOUSE INTERPHOTORECEPTOR MATRIX; VESTIBULAR SENSORY APPARATUS; MECHANICAL TRANSDUCTION; STRUCTURAL BASIS; ACTIN-FILAMENTS; PROTEOGLYCANS; MICROTUBULES; ORGANIZATION; TUBULIN; ORGAN AB Through thin-section and freeze-fracture electron microscopy, we identify structural correlates of an intense vesicular traffic in a narrow band of cytoplasm around the cuticular plate of the bullfrog vestibular hair cells. Myriads of coated and uncoated vesicles associated with longitudinally oriented microtubules populate the narrow cytoplasmic region between the cuticular plate and the actin network of the apical junctional belt, If microtubules in the sensory hair cells, like those in axons, are pathways for organelle transport, then the characteristic distribution of microtubules around the cuticular plate represents transport pathways across the apical region of the hair cells. This compartmentalized membrane traffic system appears to support an intense vesicular release and uptake along a band of apical plasma membrane near the cell border. Functions of this transport system may include membrane recycling as well as exocytotic and endocytotic exchange between the hair cell cytoplasm and the endolymphatic compartment. RP Kachar, B (reprint author), NATL INST DEAFNESS & OTHER COMMUN DISORDERS, SECT STRUCT CELL BIOL, NIH, BLDG 36 5D 15, BETHESDA, MD 20892 USA. NR 21 TC 58 Z9 59 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD MAY PY 1997 VL 107 IS 1-2 BP 102 EP 112 DI 10.1016/S0378-5955(97)00027-0 PG 11 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA WZ418 UT WOS:A1997WZ41800011 PM 9165351 ER PT J AU Ferreira, MR Gammal, SH Jones, EA AF Ferreira, MR Gammal, SH Jones, EA TI Resistance to 3-mercaptopropionic acid-induced seizures in hepatic encephalopathy SO HEPATO-GASTROENTEROLOGY LA English DT Article DE hepatic encephalopathy; gamma aminobutyric acid; 3-mecaptopropionic acid; thioacetamide; fulminant hepatic failure; seizures; intracerebroventricular injection ID BENZODIAZEPINE RECEPTOR LIGANDS; RABBIT MODEL; ANIMAL-MODEL; GLUTAMATE DECARBOXYLASE; BRAIN; GABA; FAILURE; RAT; PATHOGENESIS; REVERSAL AB Background/Aims: To determine if a model of hepatic encephalopathy (HE) exhibits decreased sensitivity to the neuronal effects of a drug that induces seizures as a consequence of decreasing GABA-mediated inhibitory neurotransmission. Materials and Methods: 3-Mercaptopropionic Acid (MPA) is an inhibitor of L-glutamate decarboxylase which catalyzes the synthesis of GABA from glutamate. MPA was administered either by intraperitoneal or intracerebroventricular injection, into rats with stage III HE due to thioacetamide-induced fulminant hepatic failure and into normal control rats. Results: When MPA was administered by intraperitoneal injection, seizure-inducing doses were similar for rats with HE and control rats. However, when a constant dose of MPA (330 mu g) was administered by intracerebroventricular injection, rats with HE took significantly longer to develop seizures than control rats (16.2 vs. 7.3 minutes; p < 0.0005). Conclusions: In a model of HE: (i) There is increased resistance to the convulsive effects of MPA; and (ii) This phenomenon is apparent when MPA is given centrally, but not when it is given peripherally. Increased resistance to the development of a complication of reduced GABA-mediated neurotransmission. induced by MPA in the model provides support for the hypothesis that HE is associated with increased GABA-mediated inhibitory neurotransmission. C1 UNIV AMSTERDAM,ACAD MED CTR,DEPT GASTROINTESTINAL & LIVER DIS,NL-1105 AZ AMSTERDAM ZO,NETHERLANDS. NIDDKD,LIVER DIS SECT,BETHESDA,MD. NR 25 TC 7 Z9 7 U1 0 U2 0 PU H G E UPDATE MEDICAL PUBL LTD. PI ATHENS PA PO BOX 17160, ATHENS GR-10024, GREECE SN 0172-6390 J9 HEPATO-GASTROENTEROL JI Hepato-Gastroenterol. PD MAY-JUN PY 1997 VL 44 IS 15 BP 766 EP 769 PG 4 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA XK539 UT WOS:A1997XK53900028 PM 9222686 ER PT J AU Omori, M Evarts, RP Omori, N Hu, ZY Marsden, ER Thorgeirsson, SS AF Omori, M Evarts, RP Omori, N Hu, ZY Marsden, ER Thorgeirsson, SS TI Expression of alpha-fetoprotein and stem cell factor/c-kit system in bile duct ligated young rats SO HEPATOLOGY LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; C-KIT; EPITHELIAL-CELLS; ADULT-RAT; HEPATOCELLULAR-CARCINOMA; HEPATIC DIFFERENTIATION; INSITU HYBRIDIZATION; LIVER DEVELOPMENT; OVAL CELLS; W-LOCUS AB The existence of a facultative hepatic stem cell compartment in bile ductules that participates in the renewal process of epithelial cell populations in the liver is well documented, The present study was undertaken to determine whether the immature bile epithelium responds differently to growth stimulus induced by bile stasis to that seen in the adult animal. In addition, the possible involvement of the growth factor/receptor systems associated with early activation of hepatic stem cells in bile duct proliferation as also examined, Bile duct ligation was used to induce the proliferation of bile epithelial cells, The expression of full-length alpha-feto-protein (AFP) was used as an indicator for activation of the stem cell compartment, AFP was highly and selectively expressed in small bile ducts 7 days after bile duct Ligation in immature rats up to 5 weeks of age, Although no significant increase in the expression of stem cell factor (SCF) c-kit, hepatocyte growth factor (HGF), and transforming growth factor-alpha (TGF-alpha) was observed 7 days after bile duct ligation in adult rats, the expression of all these growth factors was increased in bile duct ligated rats up to 5 weeks of age. These results suggest that the bile ductular epithelium in the young rats responds to bile stasis in a fashion that is phenotypically similar to that seen during early activation of hepatic stem cells in adult liver. C1 NCI,EXPT CARCINOGENESIS LAB,DBS,NIH,BETHESDA,MD 20892. NR 57 TC 64 Z9 65 U1 0 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 MAY PY 1997 VL 25 IS 5 BP 1115 EP 1122 DI 10.1002/hep.510250512 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WX604 UT WOS:A1997WX60400013 PM 9141427 ER PT J AU Issaragrisil, S Kaufman, D Thongput, A Chansung, K Thamprasit, T Piankijagum, A Anderson, T Shapiro, S Leaverton, P Young, NS AF Issaragrisil, S Kaufman, D Thongput, A Chansung, K Thamprasit, T Piankijagum, A Anderson, T Shapiro, S Leaverton, P Young, NS TI Association of seropositivity for hepatitis viruses and aplastic anemia in Thailand SO HEPATOLOGY LA English DT Article ID VIRAL-HEPATITIS; NON-A; NON-B; PATHOGENESIS; DIAGNOSIS; PROGNOSIS AB Aplastic anemia is more common in the Orient than in western countries, with an incidence in Thailand that is 2- to 3-fold higher than in Europe, Aplastic anemia after hepatitis is a well characterized clinical entity, and clinical hepatitis is also prevalent in the Far East. We performed a prospective case control study to determine risk factors for aplastic anemia in Bangkok and two rural regions during 1989 to 1994, A total of 375 cases were identified, along with 1,174 hospital controls matched for age and sex, Historical data were collected by trained interviewers, Sera from a subset of cases (N = 177) and controls (N = 183) were tested for antibodies to hepatitis viruses A, B, and C and hepatitis B surface antigen. There was no evidence of association of aplastic anemia with hepatitis B or hepatitis C. Previous exposure to hepatitis A, as determined by immunoglobulin G (IgG) seropositivity, was significantly associated with aplastic anemia: the relative risk adjusted for confounding was 2.9 (95% confidence interval 1.2-6.7), The same association also existed for persons under age 25 years, in whom the prevalence of hepatitis A IgG was lower than in the total population, However, no patients showed evidence of recent infection with hepatitis A (immunoglobulin M [IgM] seropositivity), These results indicate that exposure to a hepatitis virus is a risk indicator for aplastic anemia in Thailand, and while itself unlikely to be etiologic, hepatitis A may be a surrogate marker for another enteric microbial agent. C1 BOSTON UNIV, SCH MED, SLONE EPIDEMIOL UNIT, BOSTON, MA 02118 USA. MAHIDOL UNIV, SIRIRAJ HOSP, DEPT MICROBIOL, BANGKOK 10700, THAILAND. KHON KAEN UNIV, DEPT MED, KHON KAEN, THAILAND. PRINCE SONGKLA UNIV, DEPT MED, SONGKHLA, THAILAND. UNIV S FLORIDA, SCH PUBL HLTH, TAMPA, FL USA. NHLBI, BETHESDA, MD 20892 USA. RP Issaragrisil, S (reprint author), MAHIDOL UNIV, SIRIRAJ HOSP, DEPT MED, DIV HEMATOL, 2 PRANNOK, BANGKOK 10700, THAILAND. OI Issaragrisil, Surapol/0000-0002-8924-0646 FU NHLBI NIH HHS [HL 35068] NR 18 TC 8 Z9 10 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD MAY PY 1997 VL 25 IS 5 BP 1255 EP 1257 DI 10.1002/hep.510250532 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WX604 UT WOS:A1997WX60400033 PM 9141447 ER PT J AU Lemon, SM Nishioka, K Mishiro, S Johnson, L AF Lemon, SM Nishioka, K Mishiro, S Johnson, L TI The 18th United States Japan Joint Hepatitis Panel Meeting SO HEPATOLOGY LA English DT Editorial Material C1 UNIV TEXAS,MED BRANCH,DEPT MICROBIOL,GALVESTON,TX 77555. VIRAL HEPATITIS RES FDN JAPAN,TOKYO,JAPAN. TOSHIBA GEN HOSP,DEPT MED SCI,TOKYO,JAPAN. NIAID,DMID,ENTER DIS BRANCH,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 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 1997 VL 25 IS 5 BP 1287 EP 1291 DI 10.1002/hep.510250542 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WX604 UT WOS:A1997WX60400042 PM 9141456 ER PT J AU Uzendoski, K Kantor, JA Abrams, SI Schlom, J Hodge, JW AF Uzendoski, K Kantor, JA Abrams, SI Schlom, J Hodge, JW TI Construction and characterization of a recombinant vaccinia virus expressing murine intercellular adhesion molecule-1: Induction and potentiation of antitumor responses SO HUMAN GENE THERAPY LA English DT Article ID T-CELL ACTIVATION; ICAM-1; LYMPHOCYTES; IMMUNITY; B7-1; COSTIMULATION; FIBROSARCOMA; BINDING; NAIVE; LFA-1 AB The intercellular adhesion molecule-1 (ICAM-1) has been associated with cellular migration into inflammatory sites and with facilitating interactions between lymphocytes and tumor targets in the pathway of cell-mediated cytotoxicity. More recently, ICAM-1 has become increasingly implicated in the costimulation of T cell functions, such as antigen-dependent T cell proliferation. Previous murine studies have shown that the introduction of the ICAM-1 gene into tumor cells using retroviral vectors led to enhanced antitumor responses. In this study, we report the construction, characterization, and immunological consequences of a recombinant vaccinia virus expressing murine ICAM-1. Vaccinia virus represents an attractive vector for the delivery of molecules such as ICAM-1 due to its wide host range, rapid infection, and functional expression of inserted gene products. The infection of tumor cells with this recombinant virus resulted in the expression of functional ICAM-1. Infected tumors provide accessory or secondary signals to lymphoblasts in vitro, resulting in enhanced cytokine production or alloreactive cytotoxic T lymphocyte (CTL) activity. In vivo, we demonstrated that weakly immunogenic syngeneic tumors, infected with and expressing rV-ICAM-1, were rejected by immunocompetent hosts. Furthermore, immunization with rV-ICAM-1-infected tumors resulted in the rejection of subsequent tumor challenge, providing evidence for recall response and immunological memory. These studies demonstrated the utility of a recombinant vaccinia virus to deliver and efficiently express ICAM-1 molecules on tumor cells for potential gene therapy and recombinant approaches to cancer immunotherapy. C1 NCI,TUMOR IMMUNOL & BIOL LAB,NIH,BETHESDA,MD 20892. NIH,HOWARD HUGHES MED INST,RES SCHOLARS PROGRAM,BETHESDA,MD 20892. RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 NR 25 TC 39 Z9 39 U1 0 U2 2 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 MAY 1 PY 1997 VL 8 IS 7 BP 851 EP 860 DI 10.1089/hum.1997.8.7-851 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WY231 UT WOS:A1997WY23100006 PM 9143911 ER PT J AU Puck, JM Middelton, L Pepper, AE AF Puck, JM Middelton, L Pepper, AE TI Carrier and prenatal diagnosis of X-linked severe combined immunodeficiency: Mutation detection methods and utilization SO HUMAN GENETICS LA English DT Article ID BONE-MARROW TRANSPLANTATION; CHROMOSOME INACTIVATION; LINKAGE; SCIDX1 AB IL2RG, the gene encoding the common gamma chain, gamma c, of the receptor for interleukin-2 and other cytokines, has been identified as the disease gene for severe combined immunodeficiency (SCID) of the X-linked type. Specific mutational diagnosis for X-linked SCID has thus become possible. For many women at risk for carrying an IL2RG mutation, no samples were saved from an affected male relative prior to either death or bone marrow transplantation (BMT). To establish optimal methods for genetic evaluation of such women, we compared mutational screening by single-strand conformational polymorphism, heteroduplex analysis and dideoxy fingerprinting (ddF). Abnormally migrating band patterns were followed up with direct sequencing for identification of specific mutations. The most sensitive method, ddF, detected heterozygous alterations, subsequently confirmed to represent significant mutations, in all of 19 unrelated obligate or suspected carriers studied. Some of these women, as well as others at risk for carrying an X-linked SCID mutation, enrolled in a study of prenatal diagnosis after fetal testing for gender determination. Originally using linkage analysis and, more recently, specific detection of IL2RG mutations, we evaluated pregnancies at risk for X-linked SCID prospectively on a research basis. Of 27 male fetuses tested 14 were predicted to be unaffected and confirmed to have normal immune status at birth. Among pregnancies predicted to be affected, 2 were terminated, while 11 affected males were born at term. Nine of these received neonatal BMT, one had BMT at 3 months of age, and one underwent a successful experimental in utero BMT. In our study cohort accurate prenatal diagnosis assisted decision making and expanded treatment options for families at risk for having infants with a severe, but treatable genetic disorder that presents early in life. C1 NIH,MED GENET BRANCH,NATL HUMAN GENOME RES INST,BETHESDA,MD 20892. RP Puck, JM (reprint author), NIH,LAB GENE TRANSFER,NATL HUMAN GENOME RES INST,BLDG 49,RM 3A14,49 CONVENT DR,MSC 4442,BETHESDA,MD 20892, USA. NR 21 TC 23 Z9 23 U1 0 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAY PY 1997 VL 99 IS 5 BP 628 EP 633 DI 10.1007/s004390050418 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA WW190 UT WOS:A1997WW19000013 PM 9150730 ER PT J AU Koper, JW Stolk, RP deLange, P Huizenga, NATM Molijn, GJ Pols, HAP Grobbee, DE Karl, M deJong, FH Brinkmann, AO Lamberts, SWJ AF Koper, JW Stolk, RP deLange, P Huizenga, NATM Molijn, GJ Pols, HAP Grobbee, DE Karl, M deJong, FH Brinkmann, AO Lamberts, SWJ TI Lack of association between five polymorphisms in the human glucocorticoid receptor gene and glucocorticoid resistance SO HUMAN GENETICS LA English DT Article ID PRIMARY CORTISOL RESISTANCE; SKIN FIBROBLASTS; PATIENT; BINDING; DNA; MUTATION; DISEASE AB Glucocorticoid resistance due to mutations in the gene for the glucocorticoid receptor has been suggested to be more common than is thought at present, owing to the relative mildness of its symptoms and the difficulty of its diagnosis. To investigate the prevalence of mutations in the glucocorticoid receptor gene responsible for relative insensitivity to glucocorticoids, we carried out polymerase chain reaction/single-strand conformation analysis of the glucocorticoid receptor gene in a group of 20, otherwise healthy, persons with a reduced response in a dexamethasone suppression test and in 20 controls. We did not find mutations or polymorphisms associated with a reduced sensitivity to glucocorticoids. However, we identified five novel polymorphisms in the gene for the human glucocorticoid receptor, which may be useful in analyzing whether loss of (part of) the glucocorticoid receptor gene plays a role in glucocorticoid-resistant malignancies. Although relative resistance to glucocorticoids seems to be rather frequent in otherwise healthy persons, it is not usually associated with mutations or polymorphisms in the glucocorticoid receptor gene. C1 ERASMUS UNIV ROTTERDAM,DEPT EPIDEMIOL & BIOSTAT,NL-3000 DR ROTTERDAM,NETHERLANDS. NICHHD,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. ERASMUS UNIV ROTTERDAM,DEPT ENDOCRINOL & REPROD,NL-3000 DR ROTTERDAM,NETHERLANDS. RP Koper, JW (reprint author), ERASMUS UNIV ROTTERDAM,HOSP DIJKZIGT,DEPT INTERNAL MED 3,ROOM BD 277,40 DR MOLEWATERPL,NL-3015 GD ROTTERDAM,NETHERLANDS. RI de Jong, Frank/A-9876-2011; Stolk, Ronald/B-2341-2013; Grobbee, Diederick/C-7651-2014 OI de Jong, Frank/0000-0003-3578-1065; Stolk, Ronald/0000-0002-0518-1205; Grobbee, Diederick/0000-0003-4472-4468 NR 26 TC 174 Z9 193 U1 0 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAY PY 1997 VL 99 IS 5 BP 663 EP 668 DI 10.1007/s004390050425 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA WW190 UT WOS:A1997WW19000020 PM 9150737 ER PT J AU Makalowski, W AF Makalowski, W TI Mermaid: A not-so-new family of human repetitive elements SO HUMAN GENETICS LA English DT Letter ID SEQUENCES RP Makalowski, W (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NIH,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. RI Makalowski, Wojciech/I-2843-2016 NR 10 TC 0 Z9 0 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 MAY PY 1997 VL 99 IS 5 BP 696 EP 697 DI 10.1007/s004390050433 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA WW190 UT WOS:A1997WW19000028 PM 9150745 ER PT J AU Goletz, TJ Klimpel, KR Leppla, SH Keith, JM Berzofsky, JA AF Goletz, TJ Klimpel, KR Leppla, SH Keith, JM Berzofsky, JA TI Delivery of antigens to the MHC class I pathway using bacterial toxins SO HUMAN IMMUNOLOGY LA English DT Review ID MAJOR HISTOCOMPATIBILITY COMPLEX; ANTHRAX PROTECTIVE ANTIGEN; PROTEASOME-RELATED GENE; PSEUDOMONAS EXOTOXIN-A; T-CELLS RECOGNIZE; DIPHTHERIA-TOXIN; LETHAL FACTOR; ADENYLATE-CYCLASE; MAMMALIAN-CELLS; LYMPHOCYTES-T AB Cytotoxic T lymphocytes (CTL) recognize antigens derived from endogenously expressed proteins presented on the cell surface in the concert of major histocompatibility complex (MHC) class I molecules. Because CTL are effective in antiviral and antitumor responses, the delivery of antigens to the class I pathway has been the focus of numerous efforts. Generating CTL by immunization with exogenous proteins is often ineffective because these antigens typically enter the MHC class II pathway. This review focuses on the usefulness of bacterial toxins for delivering antigens to the MHC class I pathway. Several toxins naturally translocate into the cytosol, where they mediate their cytopathic effects, and the mechanisms by which this occurs has been elucidated. Molecular characterization of these toxins identified the functional domains and enabled the generation of modified proteins that were no longer toxic but retained the ability to translocate into the cytosol. Thus, these modified toxins could be examined for their ability to carry peptides or whole proteins into che cytosolic processing pathway. Of the toxins studied-diphtheria, pertussis, Pseudomonas, and anthrax-the anthrax toxin appears the most promising in its ability to deliver large protein antigens and its efficiency of translocation. C1 NCI,METAB BRANCH,MOL IMMUNOGENET & VACCINE RES SECT,DIV CLIN SCI,NIH,BETHESDA,MD 20892. NIDR,ORAL INFECT & IMMUN BRANCH,NIH,BETHESDA,MD 20892. NR 90 TC 57 Z9 61 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD MAY PY 1997 VL 54 IS 2 BP 129 EP 136 DI 10.1016/S0198-8859(97)00081-5 PG 8 WC Immunology SC Immunology GA XV228 UT WOS:A1997XV22800004 PM 9297531 ER PT J AU Castellino, F Zhong, GM Germain, RN AF Castellino, F Zhong, GM Germain, RN TI Antigen presentation by MHC class II molecules: Invariant chain function, protein trafficking, and the molecular basis of diverse determinant capture SO HUMAN IMMUNOLOGY LA English DT Review ID MAJOR HISTOCOMPATIBILITY COMPLEX; GLUT4 GLUCOSE-TRANSPORTER; HLA-DR MOLECULES; PEPTIDE-BINDING; INTRACELLULAR-TRANSPORT; ENDOPLASMIC-RETICULUM; SURFACE EXPRESSION; ENDOCYTIC PATHWAY; CYTOPLASMIC TAIL; 3-DIMENSIONAL STRUCTURE AB Major histocompatibility complex class II molecules are heterodimeric integral membrane proteins whose primary function is the presentation of antigenic peptides derived from proteins entering the endocytic pathway to CD4(+) T lymphocytes. To accomplish this physiologic function, class II molecules must assemble in the secretory pathway without undergoing irreversible ligand association at that sire, traffic efficiently to the endocytic pathway, and productively interact with protein ligands in these organelles before their ultimate expression on the plasma membrane. Here we review our work describing how invariant chain promotes the assembly and transport process, the complex itinerary of class II invariant chain complexes through the endocytic pathway, the role of large protein fragments as substrates for class II binding, and the existence of a second pathway for antigen capture by mature class II molecules that complements that involving newly synthesized dimers. We integrate these observations into a coherent model for the operation of a class II-dependent antigen processing and presentation system able to capture diverse antigenic determinants present in proteins of varying structure. C1 NIAID,IMMUNOL LAB,LYMPHOCYTE BIOL SECT,NIH,BETHESDA,MD 20892. NR 88 TC 78 Z9 82 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD MAY PY 1997 VL 54 IS 2 BP 159 EP 169 DI 10.1016/S0198-8859(97)00078-5 PG 11 WC Immunology SC Immunology GA XV228 UT WOS:A1997XV22800007 PM 9297534 ER PT J AU Thompson, DB Ravussin, E Bennett, PH Bogardus, C AF Thompson, DB Ravussin, E Bennett, PH Bogardus, C TI Structure and sequence variation at the human leptin receptor gene in lean and obese Pima Indians SO HUMAN MOLECULAR GENETICS LA English DT Article ID SECONDARY STRUCTURE; DIABETES-MELLITUS; MESSENGER-RNAS; PATHOGENESIS; PRECURSORS; LINKAGE; MICE AB The cloning of human and mouse cDNAs from brain that encode high affinity leptin receptors was recently reported, We have physically localized the human leptin receptor gene (LEPR) to a region at 1p31, between the anonymous microsatellite markers D1S515 and D1S198, The genomic structure of the human leptin receptor gene, corresponding to the published human brain cDNA sequence, spans over 70 kb and includes 20 exons, Since the leptin receptor gene is a candidate gene for obesity, and because of its proximity to D1S198, a marker previously linked to insulin secretion, the LEPR gene was sequenced in 20 non-diabetic Pima Indians chosen for extremes in percent body fat and in their acute insulin response to intravenous glucose, Seven polymorphic sites were identified, Two of these polymorphisms, Lys109Arg and Gln223Arg, are amino acid substitutions in the extracellular domain of the leptin receptor, one polymorphism is a silent substitution, and four occur in non-coding regions of the leptin receptor, Four of these sites are in linkage disequilibrium with one another, Nucleotides at th ree noncoding polymorphic sites were found exclusively in obese Pima Indians, This demonstrates an association between variation at the leptin receptor gene and obesity in humans. RP Thompson, DB (reprint author), NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,NIH,4212 N 16TH ST,PHOENIX,AZ 85016, USA. NR 32 TC 94 Z9 101 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY PY 1997 VL 6 IS 5 BP 675 EP 679 DI 10.1093/hmg/6.5.675 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA WX608 UT WOS:A1997WX60800005 PM 9158141 ER PT J AU Vortmeyer, AO Gnarra, JR EmmertBuck, MR Katz, D Linehan, WM Oldfield, EH Zhuang, Z AF Vortmeyer, AO Gnarra, JR EmmertBuck, MR Katz, D Linehan, WM Oldfield, EH Zhuang, Z TI von Hippel-Lindau gene deletion detected in the stromal cell component of a cerebellar hemangioblastoma associated with von Hippel-Lindau disease SO HUMAN PATHOLOGY LA English DT Article DE hemangioblastoma; VHL gene; loss of heterozygosity; tissue microdissection ID ENDOTHELIAL GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; CAPILLARY HEMANGIOBLASTOMA; HISTOGENESIS; EXPRESSION; TUMOR AB Central nervous system hemangioblastoma is a neoplasm with characteristic and well-described histopathological features, including proliferation of vascular and stromal cells. Yet, the histogenesis of the stromal cell component and its neoplastic capacity as compared with the vascular component are still controversial. Stromal cells were selectively procured from formalin-fixed, paraffin-embedded archival tissue from a von Hippel-Lindau (VHL) disease patient with a cerebellar hemangioblastoma and studied for loss of heterozygosity (LOH) of the VHL gene locus and associated microsatellite regions. The stromal cells consistently showed LOH. Analysis of mixed stromal and vascular areas of this tumor and four other hemangioblastomas of VHL patients showed that loss of heterozygosity was partially obscured. These preliminary results suggest that the stromal component of hemangioblastomas contains genetic alterations consistent with a neoplastic nature. Additional samples of pure stromal cells need to be analyzed to establish the prevalence of VHL gene deletion in stromal cells of capillary hemangioblastoma and, hence, its pathogenetic significance. Copyright (C) 1997 by W.B. Saunders Company. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. NINCDS,OFF CLIN DIRECTOR,BETHESDA,MD 20892. NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. NR 20 TC 126 Z9 130 U1 0 U2 0 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 MAY PY 1997 VL 28 IS 5 BP 540 EP 543 DI 10.1016/S0046-8177(97)90075-7 PG 4 WC Pathology SC Pathology GA XA030 UT WOS:A1997XA03000006 PM 9158701 ER PT J AU Naresh, KN OConor, GT Soman, CS Johnson, J Advani, SH MaGrath, IT Bhatia, KG AF Naresh, KN OConor, GT Soman, CS Johnson, J Advani, SH MaGrath, IT Bhatia, KG TI A study of p53 protein, proliferating cell nuclear antigen, and p21 in Hodgkin's disease at presentation and relapse SO HUMAN PATHOLOGY LA English DT Article DE Hodgkin's disease; lymphoma; relapse; p53 protein; proliferating cell nuclear antigen; p21; waf/cip 1 ID TUMOR-SUPPRESSOR GENE; ABNORMAL EXPRESSION; LYMPHOMA; P53-PROTEIN; MUTATIONS; INDUCTION; BCL-2; MDM2; PCNA AB About one fourth of patients with Hodgkin's disease relapse after therapy. The mechanisms that lead to resistance to treatment in these patients are poorly understood. The authors describe the differential protein expression of p53, proliferating cell nuclear antigen (PCNA), and p21 at initial presentation and relapse, and discuss their role in disease progression and resistance to therapy. Thirty-four patients with Hodgkin's disease who had relapsed after standard chemotherapy and radiotherapy regimens were assessed for the expression of p53 protein, PCNA, and p21 protein (waf/cip 1). Tn 14 of these cases, sequential biopsies performed both at presentation and at relapse were available for the study. Seventy-five percent of the cases were positive for the p53 protein. Tumors at relapse had big-her p53 and PCNA scores than those at initial presentation. In the paired samples, a significant increase was noted in the number of p53 and PCNA-positive cells and in the intensity of staining with p53 antibody. Six of seven paired samples tested for p21 showed an increased p21 expression at relapse. These results suggest that, at relapse, Reed-Sternberg (RS) cells and their variants positive for p53, PCNA, and p21 are increased in number and individually have an increased expression of p53, PCNA and p21 proteins. These findings suggest that therapy failure and relapse may, at least in part, be associated with altered p53, p21, and PCNA pathways. C1 TATA MEM HOSP,DEPT MED ONCOL,BOMBAY 400012,MAHARASHTRA,INDIA. NCI,LYMPHOMA BIOL SECT,NIH,BETHESDA,MD 20892. RP Naresh, KN (reprint author), TATA MEM HOSP,DEPT PATHOL,BOMBAY 400012,MAHARASHTRA,INDIA. NR 29 TC 17 Z9 18 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 1997 VL 28 IS 5 BP 549 EP 555 DI 10.1016/S0046-8177(97)90077-0 PG 7 WC Pathology SC Pathology GA XA030 UT WOS:A1997XA03000008 PM 9158703 ER PT J AU Olsen, JH Sorensen, HT Friis, S McLaughlin, JK Steffensen, FH Nielsen, GL Andersen, M Fraumeni, JF Olsen, J AF Olsen, JH Sorensen, HT Friis, S McLaughlin, JK Steffensen, FH Nielsen, GL Andersen, M Fraumeni, JF Olsen, J TI Cancer risk in users of calcium channel blockers SO HYPERTENSION LA English DT Article DE calcium channel blockers; apoptosis; neoplasms; epidemiology; cohort studies ID CELL-DEATH; SURVIVAL AB Ca2+ channel blockers may cause cancer by inhibiting apoptosis or reducing intracellular Ca2+ in certain tissues. Recent findings suggest that drug users are at increased risk for cancer in general and for colon cancer in particular. We conducted a study in one Danish county of 17 911 patients who received at least one prescription of Ca2+ channel blockers between 1 January 1991 and 31 December 1993. The patients were identified from records in the National Health Insurance Program, which refunds part of the price of such drugs. Cancer occurrence and rate were determined by use of the files of the Danish Cancer Registry and compared with county-specific incidence rates for various categories of cancer. During the follow-up period of up to 3 years, 412 cancers were observed among users of Ca2+ channel blockers, compared with 414 expected, to yield an age- and sex-standardized incidence ratio (SIR) of 1.00 (95% confidence interval, 0.90 to 1.10). There was no indication of an excess risk in the subgroup of likely long-term users or users of specific drugs. The SIR of colon cancer, a site of a priori interest, was 0.8 (95% confidence interval, 0.5 to 1.1) on the basis of 34 cases. Although the results are reassuring, the lack of association could reflect the relatively short follow-up after registration in the prescription database. Continued monitoring of cancer risk is planned. C1 AARHUS UNIV,DANISH EPIDEMIOL SCI CTR,DK-8000 AARHUS C,DENMARK. AARHUS UNIV,DEPT INTERNAL MED 5,DK-8000 AARHUS C,DENMARK. INT EPIDEMIOL INST,ROCKVILLE,MD. AALBORG HOSP,DEPT INTERNAL MED M,AALBORG,DENMARK. ODENSE UNIV,DEPT CLIN PHARMACOL,ODENSE,DENMARK. NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. RP Olsen, JH (reprint author), DANISH CANC SOC,DIV CANC EPIDEMIOL,STRANDBLVD 49,DK-2100 COPENHAGEN 0,DENMARK. RI Andersen, Morten/H-3555-2011; OI Andersen, Morten/0000-0001-7029-2860; Steffensen, Flemming Hald/0000-0003-0252-6631 NR 28 TC 92 Z9 92 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAY PY 1997 VL 29 IS 5 BP 1091 EP 1094 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA WX765 UT WOS:A1997WX76500005 PM 9149671 ER PT J AU Chandra, R Optican, LM AF Chandra, R Optican, LM TI Detection, classification, and superposition resolution of action potentials in multiunit single-channel recordings by an on-line real-time neural network SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE multiunit spike sorting; neural networks; online; real-time discrimination ID UNSUPERVISED WAVEFORM CLASSIFICATION; INTRAFASCICULAR RECORDINGS; MULTINEURON RECORDINGS; REPETITIVE VECTORS; SIGNALS; ELECTROMYOGRAPHY; IMPLEMENTATION; DISCRIMINATOR; RECOGNITION; SEPARATION AB Determination of single-unit spike trains from multiunit recordings obtained during extracellular recording has been the focus of many studies over the last two decades. In multiunit recordings, superpositions can occur with high frequency if the firing rates of the neurons are high or correlated, making superposition resolution imperative for accurate spike train determination. In this work, a connectionist neural network (NN) was applied to the spike sorting challenge. A novel training scheme was developed which enabled the NN to resolve some superpositions using single-channel recordings. Simulated multiunit spike trains were constructed from templates and noise segments that were extracted from real extracellular recordings. The simulations were used to determine the performances of the NN and a simple matched template filter (MTF), which was used as a basis for comparison. The network performed as well as the MTF in identifying nonoverlapping spikes, and was significantly better in resolving superpositions and rejecting noise. An on-line, real-time implementation of the NN discriminator, using a high-speed digital signal processor mounted inside an IBM-PC, is now in use in six laboratories. C1 NEI,SENSORIMOTOR RES LAB,NIH,BETHESDA,MD 20892. NR 43 TC 76 Z9 83 U1 0 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD MAY PY 1997 VL 44 IS 5 BP 403 EP 412 DI 10.1109/10.568916 PG 10 WC Engineering, Biomedical SC Engineering GA WU736 UT WOS:A1997WU73600010 PM 9125825 ER PT J AU Candeias, S Muegge, K Durum, SK AF Candeias, S Muegge, K Durum, SK TI IL-7 receptor and VDJ recombination: Trophic versus mechanistic actions SO IMMUNITY LA English DT Review ID REGION GENE SEGMENTS; SEVERE COMBINED IMMUNODEFICIENCY; THYMOCYTES IN-VIVO; MICE LACKING JAK3; T-LINEAGE CELLS; PRE-B-CELLS; GAMMA-CHAIN; V(D)J RECOMBINATION; TRANSGENIC MICE; ALPHA-BETA C1 NCI,SAIC,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NCI,MOL IMMUNOREGULAT LAB,FREDERICK,MD 21702. NR 101 TC 86 Z9 86 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 1997 VL 6 IS 5 BP 501 EP 508 DI 10.1016/S1074-7613(00)80338-6 PG 8 WC Immunology SC Immunology GA XB819 UT WOS:A1997XB81900001 PM 9175828 ER PT J AU Shiratori, T Miyatake, S Ohno, H Nakaseko, C Isono, K Bonifacino, JS Saito, T AF Shiratori, T Miyatake, S Ohno, H Nakaseko, C Isono, K Bonifacino, JS Saito, T TI Tyrosine phosphorylation controls internalization of CTLA-4 by regulating its interaction with clathrin-associated adaptor complex AP-2 SO IMMUNITY LA English DT Article ID CYTOPLASMIC TAIL; CD28 RECEPTOR; T-CELLS; SIGNAL AB CTLA-4 is a costimulation receptor that binds to the same ligands, CD80 and CD86, as CD28 with high affinity and is transiently expressed on the cell surface of activated T cells. CTLA-4 delivers an inhibitory signal through association of a phosphotyrosine-containing motif in the cytoplasmic domain with Syp tyrosine phosphatase. We now demonstrate that CTLA-4 interacts with the mu(2) subunit of the plasma membrane-associated adaptor complex, AP-2, through the same motif involved in the interaction with Syp, except that the interaction with mu(2) requires unphosphorylated tyrosine. The interaction with mu(2) likely induces rapid internalization of CTLA-4 from the cell surface. Our results suggest that the phosphorylation state of a single tyrosine residue determines whether CTLA-4 delivers a negative signal or is internalized. C1 CHIBA UNIV,SCH MED,CTR BIOMED SCI,DIV MOL GENET,CHUO KU,CHIBA 280,JAPAN. CHIBA UNIV,SCH MED,DEPT SURG 2,CHUO KU,CHIBA 280,JAPAN. NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892. RI Saito, Takashi/C-9684-2009; Ohno, Hiroshi/L-7899-2014; OI Saito, Takashi/0000-0001-9495-3547; Ohno, Hiroshi/0000-0001-8776-9661; Bonifacino, Juan S./0000-0002-5673-6370 NR 20 TC 216 Z9 219 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 1997 VL 6 IS 5 BP 583 EP 589 DI 10.1016/S1074-7613(00)80346-5 PG 7 WC Immunology SC Immunology GA XB819 UT WOS:A1997XB81900009 PM 9175836 ER PT J AU Martin, BK Chin, KC Olsen, JC Skinner, CA Dey, A Ozato, K Ting, JPY AF Martin, BK Chin, KC Olsen, JC Skinner, CA Dey, A Ozato, K Ting, JPY TI Induction of MHC class I expression by the MHC class II transactivator CIITA SO IMMUNITY LA English DT Article ID BARE LYMPHOCYTE SYNDROME; DR-ALPHA GENE; NF-KAPPA-B; INTERFERON-GAMMA; HLA-DM; CONSENSUS SEQUENCE; REGULATORY ELEMENT; TAP-1 EXPRESSION; CARCINOMA-CELLS; COMPLEX AB Major histocompatibility complex (MHC) class I-deficient cell lines were used to demonstrate that the MHC class II transactivator (CIITA) can induce surface expression of MHC class I molecules. CIITA induces the promoter of MHC class I heavy chain genes. The site alpha DNA element is the target for CIITA-induced transactivation of class I. In addition, interferon-gamma (IFN gamma)-induced MHC class I expression also requires an intact site alpha. The G3A cell line, which is defective in CIITA induction, does not induce MHC class I antigen and promoter in response to IFN gamma. Trans-dominant-negative forms of CIITA reduce class I MHC promoter function and surface antigen expression. Collectively, these data argue that CIITA has a role in class I MHC gene induction. C1 UNIV N CAROLINA,CYST FIBROSIS PULM RES & TREATMENT CTR,DEPT IMMUNOL MICROBIOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,CYST FIBROSIS PULM RES & TREATMENT CTR,DEPT BIOCHEM & BIOPHYS,CHAPEL HILL,NC 27599. UNIV N CAROLINA,CYST FIBROSIS PULM RES & TREATMENT CTR,DEPT MED,CHAPEL HILL,NC 27599. NICHHD,LAB MOL GROWTH REGULAT,NIH,BETHESDA,MD 20892. RP Martin, BK (reprint author), UNIV N CAROLINA,CYST FIBROSIS PULM RES & TREATMENT CTR,LINEBERGER COMPREHENS CANC CTR,CHAPEL HILL,NC 27599, USA. OI Martin, Brian/0000-0002-4873-5351 FU NCI NIH HHS [F32 CA67480-02]; NCPDCID CDC HHS [NCI48185]; NIAID NIH HHS [AI29564] NR 54 TC 152 Z9 155 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 1997 VL 6 IS 5 BP 591 EP 600 DI 10.1016/S1074-7613(00)80347-7 PG 10 WC Immunology SC Immunology GA XB819 UT WOS:A1997XB81900010 PM 9175837 ER PT J AU Mackall, CL Hakim, FT Gress, RE AF Mackall, CL Hakim, FT Gress, RE TI T-cell regeneration: All repertoires are not created equal SO IMMUNOLOGY TODAY LA English DT Review ID BONE-MARROW TRANSPLANTATION; VERSUS-HOST DISEASE; IMMUNODEFICIENCY-VIRUS INFECTION; PERIPHERAL LYMPHOCYTES-T; ATHYMIC NUDE RATS; CHRONIC GRAFT; IMMUNOGLOBULIN-SYNTHESIS; INTERLEUKIN-2 PRODUCTION; INTENSIVE CHEMOTHERAPY; HOMEOSTATIC REGULATION AB The importance of the thymus for T-cell development is a central tenet of modern immunology, but thymic-independent T-cell generation has also been described. Recent human studies have shown that the balance between thymic-dependent and thymic-independent pathways of T-cell regeneration is primarily determined by age, and that thymic-independent pathways are generally inadequate for restoration of host immunocompetence. C1 NCI,MED BRANCH,NIH,BETHESDA,MD 20892. NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. RP Mackall, CL (reprint author), NCI,PEDIAT ONCOL BRANCH,NIH,BETHESDA,MD 20892, USA. NR 69 TC 193 Z9 194 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD MAY PY 1997 VL 18 IS 5 BP 245 EP 251 DI 10.1016/S0167-5699(97)81664-7 PG 7 WC Immunology SC Immunology GA WX773 UT WOS:A1997WX77300011 PM 9153957 ER PT J AU Chang, YC Cherniak, R Kozel, TR Granger, DL Morris, LC Weinhold, LC KwonChung, KJ AF Chang, YC Cherniak, R Kozel, TR Granger, DL Morris, LC Weinhold, LC KwonChung, KJ TI Structure and biological activities of acapsular Cryptococcus neoformans 602 complemented with the CAP64 gene SO INFECTION AND IMMUNITY LA English DT Article ID NECROSIS-FACTOR-ALPHA; NITRIC-OXIDE; HUMAN SERUM; LEISHMANIA-MAJOR; CYTO-TOXICITY; IFN-GAMMA; ACTIVATION; VIRULENCE; C3; GLUCURONOXYLOMANNAN AB The extracellular polysaccharide capsule of Cryptococcus neoformans is a well-recognized virulence fatter, Strain 602 is an acapsular clinical isolate of unknown serotype which has been widely used in studies of virulence and host-parasite interactions, In previous studies, strain 602,vas compared with genetically unr elated related strains of various serotypes because the wild-type equivalent of strain 602 was not available. We created an encapsulated strain, TYCC38-602, by transforming strain 602 with the CAP64 gene which was isolated from a serotype D strain. Serological tests and chemical analysis of the major polysaccharide capsule of TYCC38-602 indicated that strain 602 was originally derived from a serotype A strain, Restoration of the ability to produce a capsule enabled strain 602 to cause fatal infection in mice, whereas the acapsular strain 602 remained aviralent. Capsule-restored yeast cells of strain 602 activated the human complement system and bound C3 fragments in a manner that is characteristic of encapsulated cryptococci, In addition, the capsule in TYCC38-602 masked the ability of the organism to induce tumor necrosis factor alpha and subsequent nitric oxide synthase production in primed macrophage-like cells, These results indicate that the lark of capsule in strain 602 is the reason for its inability to cause fatal infection. Moreover, the acapsular phenotype accounts for differences in various biological activities of strain 602 compared to encapsulated strains, The results also indicate that the gene product of CAP64 does not contribute to serotype specificity of capsules in C. neoformans. C1 NIAID,LCI,NIH,BETHESDA,MD 20892. GEORGIA STATE UNIV,DEPT CHEM,ATLANTA,GA 30303. UNIV NEVADA,SCH MED,DEPT MICROBIOL,RENO,NV 89557. UNIV UTAH,SCH MED,DIV INFECT DIS,SALT LAKE CITY,UT 84132. FU NIAID NIH HHS [AI 14209]; PHS HHS [31769] NR 35 TC 28 Z9 30 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1997 VL 65 IS 5 BP 1584 EP 1592 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WW398 UT WOS:A1997WW39800003 PM 9125534 ER PT J AU Mahanty, S Ravichandran, M Raman, U Jayaraman, K Kumaraswami, V Nutman, TB AF Mahanty, S Ravichandran, M Raman, U Jayaraman, K Kumaraswami, V Nutman, TB TI Regulation of parasite antigen-driven immune responses by interleukin-10 (IL-10) and IL-12 in lymphatic filariasis SO INFECTION AND IMMUNITY LA English DT Article ID T-CELL PROLIFERATION; HELMINTH INFECTIONS; SCHISTOSOMA-MANSONI; DOWN-REGULATION; BANCROFTIAN FILARIASIS; CYTOKINE PRODUCTION; INTERFERON-GAMMA; BRUGIA-MALAYI; IN-VITRO; MACROPHAGES AB We investigated the mechanisms by which interleukin-10 (IL-10) regulates antigen-specific haporesponsiveness in asymptomatic microfilaremic (MF) individuals. Peripheral blood mononuclear cells from MF individuals (n = 11) were stimulated in vitro with Brugia malayi antigen (BMA) or mycobacterial purified protein derivative (PPD) in the presence of neutralizing anti-IL-10 or isotype control monoclonal antibodies. As expected, BMA stimulated little or no gamma interferon (IFN-gamma) secretion in MF individuals, whereas PPD stimulated IFN-gamma in all but one. Neutralization of endogenous BMA-driven IL-10 secretion led to augmentation of IFN-gamma in seven of nine RIF individuals (1.5- to 10-fold) and did so in a BMA-specific manner (PPD-driven IFN-gamma was augmented in only two of eight MF individuals and only 1.5- to 2-fold), indicating that IL-10 downregulates type 1 responses in these individuals. Type 2 responses (IL-5 secretion) were unaffected by the IL-10 blockade, To assess whether IL-12 could reverse the type 1 downregulation observed, the effect of recombinant human IL-12 (rhIL-12) on BMA-driven IL-5 and IFN-gamma production was also evaluated, rhIL-12 augmented both BMA- and PPD-driven IFN-gamma production 5- to 10-fold in six of nine MF individuals. These data demonstrate that IL-10 downregulates BMA-driven type 1 responses and that IL-12 can overcome downregulation of Th1 responses associated with MF but does so in a non-antigen-specific manner. C1 NIAID,LPD,HELMUNTH IMMUNOL SECT,NIH,BETHESDA,MD 20892. ICMR,TB RES CTR,MADRAS,TAMIL NADU,INDIA. RI Ravichandran, Manickam/A-7128-2011; OI Mahanty, Siddhartha/0000-0003-1068-0524 NR 52 TC 74 Z9 75 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1997 VL 65 IS 5 BP 1742 EP 1747 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WW398 UT WOS:A1997WW39800025 PM 9125556 ER PT J AU Lange, BJ Weiman, M Feuer, EJ Jakobowski, D Bilodeau, J Stallings, VA Hirschl, R Bell, LM Harper, J Cnaan, A AF Lange, BJ Weiman, M Feuer, EJ Jakobowski, D Bilodeau, J Stallings, VA Hirschl, R Bell, LM Harper, J Cnaan, A TI Impact of changes in catheter management on infectious complications among children with central venous catheters SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID CANCER-PATIENTS; BLOOD CULTURE; RANDOMIZED TRIAL; SEPSIS; PREVENTION; BACTEREMIA; CHEMOTHERAPY; COLONIZATION; EFFICACY; TUBE AB OBJECTIVES: To characterize and enumerate central venous catheter (CVC)-related complications among children with chronic illnesses, and to reduce the complication rate through changes in CVC management and education. DESIGN: A prospective observational study followed by an educational program and a nonrandomized interventional trial. SETTING: The Children's Hospital of Philadelphia, a tertiary, pediatric facility. PATIENTS: 268 children with Broviac, Hickman, or Infusaport catheters in place during 58,290 catheter days. INTERVENTIONS: Development and implementation of protocols for cleaning insertion site and hub, use of nonocclusive dressings, and manipulation of access; formal staff and parental education about protocols. RESULTS: CVC-related infections fell from 4.58/1,000 catheter-days preintervention to 3.83 postintervention (risk ratio [RR], 0.20; 95% confidence interval [CI95], 0.89-1.622; P=.25); exit-site infections fell from 0.58 to 0.11 (CI95, 1.22-45.64; P=.02); rates among infants on the surgical service fell from 15.46 to 6.67 (RR, 2.31; CI95, 1.10-4.30; P=.02). CONCLUSIONS: Education and changes in management protocols reduced the incidence of exit-site infections among all patients and reduced the overall infectious complication rate among the infants receiving parenteral nutrition on the surgical service. Other interventions are needed to decrease further the infectious complications in these children. C1 CHILDRENS HOSP PHILADELPHIA,DEPT PEDIAT,PHILADELPHIA,PA 19104. CHILDRENS HOSP PHILADELPHIA,DEPT NURSING,PHILADELPHIA,PA 19104. CHILDRENS HOSP PHILADELPHIA,DEPT SURG,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. NCI,DIV CANC PREVENT & CONTROL,SURVEILLANCE PROGRAM,BETHESDA,MD 20892. CORNING PACT INC,RADNOR,PA. NR 34 TC 13 Z9 17 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD MAY PY 1997 VL 18 IS 5 BP 326 EP 332 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA WY684 UT WOS:A1997WY68400007 PM 9154475 ER PT J AU Guo, WX Burger, AM Fischer, RT Sieckmann, DG Longo, DL Kenny, JJ AF Guo, WX Burger, AM Fischer, RT Sieckmann, DG Longo, DL Kenny, JJ TI Sequence changes at the V-D junction of the V(H)1 heavy chain of anti-phosphocholine antibodies alter binding to and protection against Streptococcus pneumoniae SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE junctional diversity; pneumococcal vaccine; T15 idiotype ID IMMUNE-DEFICIENT MICE; III PNEUMOCOCCAL POLYSACCHARIDE; VARIABLE REGION GENE; PHOSPHORYLCHOLINE ANTIBODIES; MONOCLONAL-ANTIBODIES; B-CELLS; SOMATIC MUTATION; MOUSE; IDIOTYPE; IGM AB X-linked immune deficient (Xid) mice fail to produce anti-phosphocholine (PC) antibodies even after immunization with Streptococcus pneumoniae. Consequently, Xid mice are extremely susceptible to infection with S. pneumoniae. PC-specific a cells appear to undergo clonal deletion in Xid mice; however, a new thymus-dependent form of PC, 6-(O-phosphocholine)hydroxyhexanoate (EPC), can rescue PC-specific B cells from the bone marrow presumably by providing T cell help before clonal deletion. Analysis of PC-specific IgG hybridomas from Xid mice revealed utilization of several V-D junctional variants of the V(H)1 gene segment rearranged to different D and J(H) gene segments. The majority of Xid anti-PC antibodies exhibit an Asp --> Gly95H replacement at the V-D junction. These Gly95H V(H)1 variants associate with kappa 1C L chains to produce anti-PC antibodies that: (i) have low relative affinity for PC, (ii) are heteroclitic for nitrophenylphosphocholine and (iii) fail to bind to or provide protection against S. pneumoniae. Single prototypic V-D variants of the T15 idiotype (Asp95H), M603 idiotype (Asn95H) and M167 idiotype (Asp95H-Ala96H) were also induced in Xid mice. The M603-like and M167-like antibodies bound to and protected against S. pneumoniae even though they exhibited K(a)s for PC which were lower than T15 idiotype(+) antibodies. These data demonstrate that small changes in the V-D junctional sequence of the T15 (V(H)1) heavy chain alter L chain usage and the structure of the PC binding site so that the PC expressed on S. pneumoniae is no longer recognized. C1 NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. USN,MED RES INST,BETHESDA,MD 20889. UNIV BRADFORD,CLIN ONCOL UNIT,BRADFORD BD7 1DP,W YORKSHIRE,ENGLAND. NCI,FREDERICK CANC RES & DEV CTR,LAB BIOCHEM PHYSIOL,FREDERICK,MD 21702. NR 54 TC 19 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAY PY 1997 VL 9 IS 5 BP 665 EP 677 DI 10.1093/intimm/9.5.665 PG 13 WC Immunology SC Immunology GA XD240 UT WOS:A1997XD24000004 PM 9184912 ER PT J AU Rosenberg, YJ Cafaro, A Brennan, T Greenhouse, JG Villinger, F Ansari, AA Brown, C McKinnon, K Bellah, S YalleyOgunro, J Elkins, WR Gartner, S Lewis, MG AF Rosenberg, YJ Cafaro, A Brennan, T Greenhouse, JG Villinger, F Ansari, AA Brown, C McKinnon, K Bellah, S YalleyOgunro, J Elkins, WR Gartner, S Lewis, MG TI Virus-induced cytokines regulate circulating lymphocyte levels during primary SIV infections SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE IFN-gamma; lymphopenia; sequestration; tumor necrosis factor-alpha ID SIMIAN IMMUNODEFICIENCY VIRUS; TUMOR-NECROSIS-FACTOR; IFN-GAMMA; IN-VIVO; T-CELLS; QUANTITATIVE-ANALYSIS; IMMUNE-DEFICIENCY; INTERFERON-GAMMA; SOOTY MANGABEYS; HIV-INFECTION AB Decline in blood CD4(+) lymphocytes during primary symptomatic infections with HIV is usually attributed to viral killing, and has not been considered in terms of altered lymphocyte migration and sequestration. We therefore sought to examine whether CD4(+) cell loss from blood of macaques undergoing an acute primary SIV infection might be due to increased synthesis of cytokines, known to profoundly affect lymphocyte trafficking, rather than to direct lymphocyte destruction by virus, The findings indicate that rapid lymphocyte depletion following acute infection is not selective for CD4(+) cells, correlates precisely with increased plasma IFN-gamma and tumor necrosis factor-alpha levels, and is reversible, CD4/CD8 ratios in lymph nodes with high viral burdens remain relatively unchanged despite lymphocyte loss from blood, Levels of cytokine mRNA measured in lymphoid organs reflect neither cytokine plasma levels nor their potential to induce sequestration, These results support a model of cytokine-induced lymphocyte extravasation to account for the acute HIV/SIV-induced CD4(+) cell lymphopenia and raise questions regarding the extent to which altered lymphocyte migration plays a role in the gradual CD4(+) cell depletion throughout infection. C1 HENRY M JACKSON FDN,ROCKVILLE,MD 20850. JOHNS HOPKINS UNIV,DEPT NEUROBIOL,BALTIMORE,MD 21287. NIAID,INFECT DIS LAB,NIH,ROCKVILLE,MD 20850. EMORY UNIV,ATLANTA,GA 30322. THERIMMUNE INC,WASHINGTON,DC 20009. RI Cafaro, Aurelio/K-5314-2016 NR 64 TC 30 Z9 30 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAY PY 1997 VL 9 IS 5 BP 703 EP 712 DI 10.1093/intimm/9.5.703 PG 10 WC Immunology SC Immunology GA XD240 UT WOS:A1997XD24000007 PM 9184915 ER PT J AU Liblau, R Steinman, L Brocke, S AF Liblau, R Steinman, L Brocke, S TI Experimental autoimmune encephalomyelitis in IL-4-deficient mice SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE autoimmunity; central nervous system; cytokines; T(h)2 T cells ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MYELIN BASIC-PROTEIN; CD4(+) T-CELLS; IMMUNE DEVIATION; ORAL TOLERANCE; TH2 CELLS; INTERLEUKIN-4; RESPONSES; DISEASE; EXPRESSION AB Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease which usually follows a monophasic course, Autoreactive T(h)1 CD4(+) T cells are responsible for the lesions, whereas autoreactive T(h)2 CD4(+) T cells can, upon adoptive transfer, suppress the disease process. However, the role of IL-4 and T(h)2 cells in the spontaneous remission of EAE and in the prevention of relapses is not known, We have addressed these issues using IL-4-deficient mice in which the differentiation of T(h)2 CD4(+) T cells is severely compromised, The clinical course of actively induced EAE was compared in IL-4+/+, IL-4+/- and IL-4-/- mice on the PL/J genetic background. No significant differences were noted between groups for the frequency, severity and duration of EAE, and the frequency of relapses, Our results indicate that IL-4, despite its well-documented regulatory role in EAE, is not necessary for the spontaneous remission of disease or for the prevention of relapses, Therefore, in the absence of IL-4, overlapping or compensatory immunoregulatory mechanisms can restrict an inflammatory response within the central nervous system. C1 STANFORD UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. STANFORD UNIV,SCH MED,DEPT NEUROL & NEUROL SCI,STANFORD,CA 94305. WEIZMANN INST SCI,DEPT IMMUNOL,IL-76100 REHOVOT,ISRAEL. NINCDS,NIB,NEUROL DIS SECT,NIH,BETHESDA,MD 20892. HOP LA PITIE SALPETRIERE,INSERM,CJF 9608,F-75013 PARIS,FRANCE. NR 36 TC 74 Z9 77 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAY PY 1997 VL 9 IS 5 BP 799 EP 803 DI 10.1093/intimm/9.5.799 PG 5 WC Immunology SC Immunology GA XD240 UT WOS:A1997XD24000018 PM 9184926 ER PT J AU Hauck, ML Coffin, DO Dodge, RK Dewhirst, MW Mitchell, JB Zalutsky, MR AF Hauck, ML Coffin, DO Dodge, RK Dewhirst, MW Mitchell, JB Zalutsky, MR TI A local hyperthermia treatment which enhances antibody uptake in a glioma xenograft model does not affect tumour interstitial fluid pressure SO INTERNATIONAL JOURNAL OF HYPERTHERMIA LA English DT Article DE interstitial fluid pressure; xenograft; hyperthermia ID SOLID TUMORS; TEMPERATURE; GROWTH; TISSUE; MACROMOLECULES; ADENOCARCINOMA; HYPERTENSION; PERMEABILITY; VASCULARITY; PERFUSION AB Solid tumours have an elevated interstitial fluid pressure (IFP) due to the lack of normal lymphatics, increased permeability of tumour vasculature and an expanding cell population within a potentially limited space. This elevated IFP has been proposed to be an important barrier to the delivery of drugs and marcromolecules. We have demonstrated that local hyperthermia (4h, 41.8 degrees C) is capable of significantly enhancing the uptake of radiolabelled monoclonal antibodies (mAbs) in D-54 MG glioma xenografts grown subcutaneously in athymic mice. To determine if this increased uptake was attributable to alterations in the tumour IFP, pressure measurements using the wick-in-needle technique were made in tumours after hyperthermia treatment. These pressure measurements were taken at various time points from 4 to 90 h following the initiation of the hyperthermia and compared with pressures taken concurrently in untreated tumours. In addition, pressures were measured following a 2 h, 41.8 degrees C hyperthermia treatment, a protocol which does not result in elevated uptake of radiolabeled mAbs. No significant differences were seen at any time point in IFP measured in the tumours receiving either hyperthermia treatment when compared with untreated tumours. Thus, we conclude that the mechanism by which this hyperthermia regimen enhances mAb uptake in this human glioma xenograft model is not due to alternations in tumour IFP. C1 DUKE UNIV,MED CTR,DEPT RADIOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT PATHOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,CANC CTR BIOSTAT,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT RADIAT ONCOL,DURHAM,NC 27710. NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [CA 42324, CA 42745]; NINDS NIH HHS [NS 20023] NR 34 TC 33 Z9 34 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0265-6736 J9 INT J HYPERTHER JI Int. J. Hyperthermia PD MAY-JUN PY 1997 VL 13 IS 3 BP 307 EP 316 DI 10.3109/02656739709023538 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA XH141 UT WOS:A1997XH14100006 PM 9222813 ER PT J AU Huang, B Rodreiguez, BL Burchfiel, CM Chyou, PH Curb, JD Sharp, DS AF Huang, B Rodreiguez, BL Burchfiel, CM Chyou, PH Curb, JD Sharp, DS TI Associations of adiposity with prevalent coronary heart disease among elderly men: The Honolulu heart program SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE body mass index; waist-to-hip circumference ratio; waist circumference; coronary heart disease ID BODY-FAT DISTRIBUTION; MIDDLE-AGED MEN; CARDIOVASCULAR-DISEASE; PHYSICAL-ACTIVITY; RISK FACTOR; ANTHROPOMETRIC MEASUREMENTS; TISSUE ACCUMULATION; LIPOPROTEIN-LIPASE; CHOLESTEROL LEVELS; SERUM-CHOLESTEROL AB OBJECTIVE: To assess associations of adiposity with prevalent coronary heart disease (CHD) among elderly men. DESIGN: A cross-sectional epidemiologic study conducted between 1997 and 7993. SUBJECTS: 3741 Japanese-American men from the Honolulu Heart Program who were 71-93 y of age. MEASUREMENTS: CHD included documented myocardial infarction (electrocardiographic and enzyme criteria), acute coronary insufficiency, angina pectoris leading to surgical treatment identified through hospital surveillance, and reported history of heart attach or angina pectoris requiring hospitalization or surgical treatment. BMI was calculated as weight in kg divided by height in square meters. Waist circumference was measured at the horizontal level of the umbilicus and WHR was a ratio of waist circumference to hip circumference measured at the horizontal level of the maximal protrusion of the gluteal muscles. RESULTS: An elevated prevalence of CHD was observed in the elderly men with high BMI WHR and waist circumference. The significant associations of BMI and waist circumference with CHD persisted after adjustment for fasting glucose, physical activity and pack-years of cigarette smoking but were no longer significant (odds ration (OR) = 1.03, 95% confidence level (CI) 0.94-1.12 and OR = 1.09, CI = 0.99-1.20, respectively) after adjustment for high density lipoprotein cholesterol (HDL-C). Also, the association of BMI with CHD was not found to be independent of abdominal adiposity. However, the associations of WHR and waist circumference remained significant (OR=1.20, Cl=1.08-1.33 and OR=1.17, C1=1.01-1.37, respectively) after additional adjustment for BMI. In addition, the association of WHR with CHD was consistently significant and independent of fasting glucose, physical activity, smoking and HDL-C (OR = 1.11, Cl=1.00-1.23). CONCLUSION: WHR is associated with CHD independent of HDL-C and BMI, whereas the relation of BMI and waist circumference with CHD may be mediated through a relation of BMI and waist circumference with HDL-C level. C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,EPIDEMIOL & BIOMETRY PROGRAM,EPIDEMIOL RES UNIT,HONOLULU,HI. MARSHFIELD MED RES FDN,MARSHFIELD,WI 54449. RP Huang, B (reprint author), UNIV HAWAII,CORP RES,HONOLULU HEART PROGRAM,DIV CLIN EPIDEMIOL,SCH MED,347 N KUAKINI ST,HONOLULU,HI 96817, USA. NR 46 TC 27 Z9 30 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD MAY PY 1997 VL 21 IS 5 BP 340 EP 348 DI 10.1038/sj.ijo.0800410 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA WV974 UT WOS:A1997WV97400002 PM 9152734 ER PT J AU Kant, AK Schatzkin, A BallardBarbash, R AF Kant, AK Schatzkin, A BallardBarbash, R TI Evening eating and subsequent long-term weight change in a national cohort SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE meal patterns; evening eating; weight change; TEF; NHANES I; NHEFS; obesity; energy intake; energy expenditure ID DIET-INDUCED THERMOGENESIS; RESTING ENERGY-EXPENDITURE; OBESITY; SMOKING; WOMEN; MEN AB OBJECTIVE: To examine the association of proportion of daily energy consumed in the evening with weight change over 10 y of follow-up. DESIGN: The data used were from the First National Health and Nutrition Examination Survey (NHANES 1, 1971-75) Epidemiologic Follow-up Study (NHEFS, 1982-84). The analytic cohort included 2580 men and 4567 women aged 25-74 y at baseline (NHANES 1, 1971-75). The proportion of energy consumed in the evening (after 5 pm) was estimated from a 24 h dietary recall obtained at baseline. Weight change was defined as the difference between the follow-up and baseline weights. RESULTS: Mean+/-s.e. of percent energy from evening food intake was 46+/-0.29 in the analytic cohort. After adjustment for multiple covariates, percent energy from evening food intake and weight change were unrelated in both men and women. CONCLUSION: Extent of evening eating was not a significant predictor of 10 y weight change in the NHEFS cohort. C1 NCI,BETHESDA,MD 20892. RP Kant, AK (reprint author), CUNY QUEENS COLL,DEPT FAMILY NUTR & EXERCISE SCI,REMSEN HALL,ROOM 306E,65-30 KISSENA BLVD,FLUSHING,NY 11367, USA. NR 21 TC 25 Z9 25 U1 1 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD MAY PY 1997 VL 21 IS 5 BP 407 EP 412 DI 10.1038/sj.ijo.0800422 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA WV974 UT WOS:A1997WV97400012 PM 9152744 ER PT J AU Lizak, MJ AF Lizak, MJ TI To the editor - Reply SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Letter RP Lizak, MJ (reprint author), NEI,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 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 MAY PY 1997 VL 38 IS 6 BP 1053 EP 1053 PG 1 WC Ophthalmology SC Ophthalmology GA WY217 UT WOS:A1997WY21700002 ER PT J AU Robison, WG Laver, NM Jacot, JL Chandler, ML York, BM Glover, JP AF Robison, WG Laver, NM Jacot, JL Chandler, ML York, BM Glover, JP TI Efficacy of treatment after measurable diabeticlike retinopathy in galactose-fed rats SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE aldose reductase; computer morphometry; diabetic retinopathy; galactose-fed rat model; intervention therapy; retinal vasculature ID ALDOSE REDUCTASE INHIBITOR; RETINAL VESSEL CHANGES; FED DOGS; PREVENTION; SORBINIL; INTERVENTION; CAPILLARIES; PROGRESSION; TOLRESTAT; MODEL AB Purpose. To determine whether the diabeticlike retinal microangiopathies of the galactose-fed rat model could be ameliorated if intervention by withdrawal of the galactose diet or treatment with the aldose reductase inhibitor AL-3152 was initiated after quantifiable microangiopathies had occurred. Methods. Weanling male Sprague-Dawley rats were randomized into five groups and fed for up to 24 months Purina laboratory chow (#5001) plus 50% starch (control [CON]), 50% D-galactose (galactose [GAL]), 50% D-galactose with AL-3152 (approximately 14 mg/kg per day) (prevention [PRV]), 50% D-galactose for 6 months followed by intervention with the inhibitor (intervention [INT]), or 50% D-galactose for 6 months followed by replacement with the 50% starch diet (withdrawal [CWD]). In rats on experimental diets and killed after 6, 18, and 24 months, one retina was prepared for transmission electron microscopy; the other was used for vessel wholemounts using elastase digestion, Capillary images were analyzed by computer morphometry. Results. At 6 months, the GAL rats exhibited statistically significant (P < 0.05) increases over CON rats in mean capillary basement membrane thickness, capillary density, and dilated channels. These parameters tended to increase with time in most groups, and the differences between GAL and age-matched CON rats were maintained at the 18- and 24-month endpoints. Although the microangiopathies were ameliorated by AL-3152 treatment from the onset (PRV) I intervention after 6 months of galactosemia with either galactose withdrawal (GWD) or addition of inhibitor (INT) showed amelioration in only some parameters at 18 months and no statistically significant benefit at the 24-month endpoint. Conclusions. Amelioration of galactose-induced retinal microangiopathies with AL-3152 in the prevention group suggests an efficacious application of aldose reductase inhibitors in treating diabetic retinopathy, provided treatment can begin soon after the onset of diabetes. Intervention after some of the earliest microscopic lesions neither halted progression of the angiopathy nor provided appreciable benefit at the 24-month follow-up. C1 GEORGETOWN UNIV,SCH MED,WASHINGTON,DC. ALCON LABS INC,FT WORTH,TX 76101. RP Robison, WG (reprint author), NEI,NIH,BLDG 6,ROOM 316,BETHESDA,MD 20892, USA. NR 39 TC 9 Z9 14 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 MAY PY 1997 VL 38 IS 6 BP 1066 EP 1073 PG 8 WC Ophthalmology SC Ophthalmology GA WY217 UT WOS:A1997WY21700006 PM 9152226 ER PT J AU Bulterys, M Landesmam, S Burns, DN Rubinstein, A Goedert, JJ AF Bulterys, M Landesmam, S Burns, DN Rubinstein, A Goedert, JJ TI Sexual behavior and injection drug use during pregnancy and vertical transmission of HIV-1 SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE vertical transmission of HIV-1; sexual behavior; injection drug use; pregnancy ID HUMAN-IMMUNODEFICIENCY-VIRUS; MONONUCLEAR CELL COCULTURES; TO-CHILD TRANSMISSION; INFANT TRANSMISSION; EARLY DIAGNOSIS; DUAL INFECTION; TYPE-1; WOMEN; REPLICATION; COCAINE AB We evaluated maternal sexual behavior and injection drug use practices as possible risk factors for vertical transmission of human immunodeficiency virus type 1 (HIV-1). Data were analyzed from the Mothers and Infants Cohort Study, a prospective study in Brooklyn and the Bronx, New York. A total of 207 mother-infant sets were enrolled between 1986 and 1991 and followed for up to 4 years after the enrollment visit during pregnancy. HIV-1 transmission occurred in 49 of 201 mother-infant sets, yielding an overall transmission rate of 24.4% (95% confidence interval (CI) = 18.7% to 31.0%). Increased frequency of vaginal intercourse after the first trimester of pregnancy was positively associated with vertical transmission of HIV-1 (trend p = 0.03). A lifetime history of injection drug use was not associated with vertical transmission. However, a history of combined cocaine and heroin injection after the first trimester of pregnancy was associated with vertical HIV-1 transmission, particularly among women with CD4(+) lymphocyte levels of 20% or higher (risk ratio = 4.0; 95% CI = 2.0 to 8.1), Cocaine and heroin injection drug use after the first trimester accounted for most of the relation between preterm birth and vertical HIV-1 transmission in this cohort. Maternal coinfection with hepatitis C virus or human T-cell lymphotropic virus types I and II could not explain these observations, because coinfection with these viruses had no detectable effect on HIV-T transmission. These results suggest that maternal sexual behavior and injection drug use practices during the second and third trimester of pregnancy may modify the risk of vertical HIV-1 transmission. C1 SUNY HLTH SCI CTR,DEPT MED,BROOKLYN,NY 11203. NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,BETHESDA,MD 20892. ALBERT EINSTEIN COLL MED,DEPT PEDIAT,BRONX,NY 10467. RP Bulterys, M (reprint author), NCI,VIRAL EPIDEMIOL BRANCH,6130 EXECUT BLVD,EPN-434,ROCKVILLE,MD 20852, USA. FU NCI NIH HHS [N0-1-CP-61013]; NICHD NIH HHS [N0-1-HD-82913, R0-1-HD-25714] NR 49 TC 29 Z9 31 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD MAY 1 PY 1997 VL 15 IS 1 BP 76 EP 82 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XH946 UT WOS:A1997XH94600012 PM 9215658 ER PT J AU Irwin, RD Chou, BJ Mellick, PW Miller, RA Mahler, J Roycroft, J AF Irwin, RD Chou, BJ Mellick, PW Miller, RA Mahler, J Roycroft, J TI Toxicity of furfuryl alcohol to F344 rats and B6C3F(1) mice exposed by inhalation SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE furfuryl alcohol; inhalation; nasal lesions ID DOSE LEVELS; VAPOR; METABOLISM AB Groups of F344 rats and B6C3F(1) mice were exposed to furfuryl alcohol vapor for 6 hours per day, 5 days per week for 14 days (0, 16, 31, 63, 125, 250 ppm) or 13 weeks (0, 2, 4, 8, 16, 32 ppm). Reduced survival was observed in the 14-day study at 250 ppm. Final mean body weights of rats and mice exposed to 125 ppm and of female mice exposed to 63 ppm were lower than controls at the end of the 14-day study; there were no significant differences in mean body weight among chemical-exposed and control groups in the 13-week study. Exposure to furfuryl alcohol had no toxicologically significant effect on organ weights in either rats or mice, and did not cause any adverse changes in hematology or serum chemistry parameters evaluated in rats in the 13-week study. Microscopic lesions associated with exposure to furfuryl alcohol were present in the nose of both rats and mice at all exposure concentrations in both the 14-day and 13-week studies. Lesions observed in the 14-day study consisted of inflammation of the nasal turbinates accompanied by necrosis and squamous metaplasia of the respiratory epithelium and necrosis and degeneration of the olfactory epithelium. Similar lesions were observed in both rats and mice in the 13-week study. In addition, squamous metaplasia and goblet cell hyperplasia of the respiratory epithelium, squamous metaplasia of the transitional epithelium and degeneration, hyperplasia and some respiratory metaplasia of the olfactory epithelium were also observed in rats in the 13-week study, and hyaline droplets in the respiratory epithelium and chronic inflammation and respiratory metaplasia in the olfactory epithelium were observed in mice in the 13-week study. In general the nasal passages of mice appeared less sensitive than those of rats at the concentrations used in the 13-week study; a no-observable-effect level was not achieved in either the 14-day or the 13-week study. (C) 1997 by John Wiley & Sons, Ltd. C1 PACIFIC NW LAB, RICHLAND, WA USA. RP Irwin, RD (reprint author), NIEHS, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 19 TC 6 Z9 6 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD MAY-JUN PY 1997 VL 17 IS 3 BP 159 EP 169 DI 10.1002/(SICI)1099-1263(199705)17:3<159::AID-JAT420>3.0.CO;2-E PG 11 WC Toxicology SC Toxicology GA XM162 UT WOS:A1997XM16200003 PM 9250537 ER PT J AU Lunsford, RD Roble, AG AF Lunsford, RD Roble, AG TI comYA, a gene similar to comGA of Bacillus subtilis, is essential for competence-factor-dependent DNA transformation in Streptococcus gordonii SO JOURNAL OF BACTERIOLOGY LA English DT Article ID NUCLEOTIDE-SEQUENCE; PROTEIN; SYSTEM; BINDING; ORGANIZATION; SECRETION; CLONING; TN4001; MUTANS; RNA AB Tn4001 mutagenesis identified a new competence gene in Streptococcus gordonii Challis designated comYA. A comYA mutant was completely deficient in transformation and exhibited decreased levels of DNA binding and hydrolysis. The deduced 319-amino-acid ComYA protein exhibited 57% similarity and 33% identity to the ComGA transporter protein of Bacillus subtilis and contained the Walker A-box motif conserved in ATP-binding proteins as well as aspartic acid heres Asp-1 and Asp-2 present in some components of the general secretory pathway of gram-negative bacteria, comYA appeased to be part of a putative operon encompassing a comGB homolog, designated comYB, together with sequences that could encode ComGC- and ComGD-like peptides designated ComYC and ComYD, respectively, as well as other components, The putative ComYC and ComYD peptides had leader sequences similar to the type IV N-methylphenylalanine pilins of gram-negative bacteria, but unlike other examples in this class, including B. subtilis, they contained an alanine at position -1 of the leader instead of the usual glycine residue. Northern analysis identified a single 6.0-kb comYA-containing transcript strictly dependent on exogenous competence factor for expression in ComA1 cells, An identical pattern of expression was seen in wild-type Challis cells grown under conditions of maximal competence but not in cells that were noncompetent. C1 NIDR,ORAL INFECT & IMMUN BRANCH,NIH,BETHESDA,MD 20892. NR 29 TC 29 Z9 30 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 1997 VL 179 IS 10 BP 3122 EP 3126 PG 5 WC Microbiology SC Microbiology GA WY116 UT WOS:A1997WY11600006 PM 9150204 ER PT J AU Wiekowski, M Miranda, M Nothias, JY DePamphilis, ML AF Wiekowski, M Miranda, M Nothias, JY DePamphilis, ML TI Changes in histone synthesis and modification at the beginning of mouse development correlate with the establishment of chromatin mediated repression of transcription SO JOURNAL OF CELL SCIENCE LA English DT Article DE histone; acetylation; mouse; embryo; repression; transcription; zygotic gene expression ID DIMENSIONAL GEL ANALYSIS; RNA-POLYMERASE-II; GENE-EXPRESSION; PREIMPLANTATION EMBRYOS; ACETYLATION SITES; DNA-REPLICATION; XENOPUS-LAEVIS; TRICHOSTATIN-A; MESSENGER-RNA; POSITIVE ROLE AB The transition from a late 1-cell mouse embryo to a 4-cell embryo, the period when zygotic gene expression begins, is accompanied by an increasing ability to repress the activities of promoters and replication origins. Since this repression can be relieved by either butyrate or enhancers, it appears to be mediated through chromatin structure. Here we identify changes in the synthesis and modification of chromatin bound histones that are consistent with this hypothesis. Oocytes, which can repress promoter activity, synthesized a full complement of histones, and histone synthesis up to the early 2-cell stage originated from mRNA inherited from the oocyte. However, while histones H3 and H4 continued to be synthesized in early 1-cell embryos, synthesis of histones H2A, H2B and H1 (proteins required for chromatin condensation) was delayed until the late 1-cell stage, reaching their maximum rate in early 2-cell embryos. Moreover, histone H4 in both 1-cell and 2-cell embryos was predominantly diacetylated (a modification that facilitates transcription). Deacetylation towards the unacetylated and monoacetylated H4 population in fibroblasts began at the late 2-cell to 4-cell stage. Arresting development at the beginning of S-phase in 1-cell embryos prevented both the appearance of chromatin-mediated repression of transcription in paternal pronuclei and synthesis of new histones. These changes correlated with the establishment of chromatin-mediated repression during formation of a 2-cell embryo, and the increase in repression from the 2-cell to 4-cell stage as linker histone H1 accumulates and core histones are deacetylated. C1 ROCHE INST MOL BIOL,ROCHE RES CTR,NUTLEY,NJ 07110. SCHERING PLOUGH RES INST,DEPT IMMUNOL,KENILWORTH,NJ 07033. WYETH AYERST RES,PEARL RIVER,NY 10965. CNRS,INST ALFRED FESSARD,F-91198 GIF SUR YVETTE,FRANCE. NICHHD,NIH,BETHESDA,MD 20892. NR 59 TC 82 Z9 85 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAY PY 1997 VL 110 BP 1147 EP 1158 PN 10 PG 12 WC Cell Biology SC Cell Biology GA XE505 UT WOS:A1997XE50500002 PM 9191039 ER PT J AU Otrin, VR McLenigan, M Takao, M Levine, AS Protic, M AF Otrin, VR McLenigan, M Takao, M Levine, AS Protic, M TI Translocation of a UV-damaged DNA binding protein into a tight association with chromatin after treatment of mammalian cells with UV light SO JOURNAL OF CELL SCIENCE LA English DT Article DE Xeroderma pigmentosum; UV light; DNA binding protein; DNA repair; chromatin ID NUCLEOTIDE EXCISION-REPAIR; PIGMENTOSUM GROUP-E; A COMPLEMENTING PROTEIN; TRANSCRIBED STRAND; NUCLEAR ANTIGEN; GROUP-C; PYRIMIDINE DIMERS; PRIMATE CELLS; ACTIVE GENES; REPLICATION AB A UV-damaged DNA binding protein (UV-DDB) is the major source of UV-damaged DNA binding activity in mammalian cell extracts. This activity is defective in at least some xeroderma pigmentosum group E (XP-E) patients; microinjection of the UV-DDB protein into their fibroblasts corrects nucleotide excision repair (NER). In an in vitro reconstituted NER system, small amounts of UV-DDB stimulate repair synthesis a few fold. After exposure to UV,mammalian cells show an early dose-dependent inhibition of the extractable UV-DDB activity; this inhibition may reflect a tight association of the binding protein with UV-damaged genomic DNA. To investigate the dynamics and location of UV-DDB with respect to damaged chromatin in vivo, we utilized nuclear fractionation and specific antibodies and detected translocation of the p127 component of UV-DDB from a loose to a tight association with chromatinized DNA immediately after UV treatment. A similar redistribution was found for other NER proteins, i.e. XPA, RP-A and PCNA, suggesting their tighter association with genomic DNA after UV. These studies revealed a specific protein-protein interaction between UV-DDB/p127 and RP-A that appears to enhance binding of both proteins to W-damaged DNA in vitro, providing evidence for the involvement of UV-DDB in the damage-recognition step of NER. Moreover, the kinetics of the reappearance of extractable UV-DDB activity after UV treatment of human cells with differing repair capacities positively correlate with the cell's capacity to repair 6-4 pyrimidine dimers (6-4 PD) in the whole genome, a result consistent with an in vivo role for UV-DDB in recognizing this type of UV lesion. C1 NICHHD,SECT DNA REPLICAT REPAIR & MUTAGENESIIS,NIH,BETHESDA,MD 20892. NR 58 TC 54 Z9 54 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAY PY 1997 VL 110 BP 1159 EP 1168 PN 10 PG 10 WC Cell Biology SC Cell Biology GA XE505 UT WOS:A1997XE50500003 PM 9191040 ER PT J AU Wu, AJ Lafrenie, RM Park, C Apinhasmit, W Chen, ZJ BirkedalHansen, H Yamada, KM StetlerStevenson, WG Baum, BJ AF Wu, AJ Lafrenie, RM Park, C Apinhasmit, W Chen, ZJ BirkedalHansen, H Yamada, KM StetlerStevenson, WG Baum, BJ TI Modulation of MMP-2 (gelatinase A) and MMP-9 (gelatinase B) by interferon-gamma in a human salivary gland cell line SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID PRIMARY SJOGRENS-SYNDROME; NECROSIS-FACTOR-ALPHA; TISSUE INHIBITOR; GENE-EXPRESSION; IV COLLAGENASE; ADHESION MOLECULES; MATRIX; METALLOPROTEINASES; LYMPHOCYTES; SECRETION AB Gelatinases have been shown to be regulated by many cytokines and growth factors, and have been implicated in the pathogenesis of certain autoimmune diseases via tissue destruction. High levels of several cytokines, including IFN-gamma and TNF-alpha, have been demonstrated in the salivary gland microenvironment of patients with Sjogren's syndrome (SS). How these cytokines may be contributing to the pathogenesis of this disease is not well understood We hypothesized that IFN-gamma with or without (+/-) TNF-alpha could be playing a role in the pathogenesis of SS via the regulation of matrix metalloproteinase (MMP) levels. This study examined the role of IFN-gamma (+) TNF-alpha in the regulation of the matrix metalloproteinases, MMP-2 (72 kD gelatinase A) and MMP-9 (92 kD gelatinase B). A human salivary gland cell line (HSG) has been used as a possible in vitro model to study the role of IFN-gamma + TNF-alpha. in the pathogenesis of SS. The HSG cell line, in the presence of IFN +/- TNF-alpha, displays increased MMP-2 and MMP-9 gelatinolytic activity, protein and RNA levels. The increase in MMP activity was partially blocked with an antibody against the IFN-gamma receptor, and this was associated with a complete inhibition of the previously described IFN-gamma +/- TNF-alpha antiproliferative effect. However, incubation of IFN-gamma treated HSG cells with the synthetic MMP inhibitor BB94 did not alleviate this antiproliferative effect. In addition, we demonstrate that there are very high levels of MMP-9 In the saliva of patients with SS when compared to healthy control subjects. These data suggest that cytokines could be regulating MMP production by salivary epithelial cells and thus indicate a potential role for these cells in the pathogenesis of SS. (C) 1997 Wiley-Liss, Inc. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,NIH,BETHESDA,MD 20892. NIDR,DEV BIOL LAB,NIH,BETHESDA,MD 20892. NIDR,ORAL MED LAB,NIH,BETHESDA,MD 20892. NIDR,MATRIX METALLOPROTEINASE UNIT,NIH,BETHESDA,MD 20892. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 41 TC 48 Z9 49 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 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAY PY 1997 VL 171 IS 2 BP 117 EP 124 DI 10.1002/(SICI)1097-4652(199705)171:2<117::AID-JCP1>3.0.CO;2-R PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA WW033 UT WOS:A1997WW03300001 PM 9130458 ER PT J AU Nawashiro, H Tasaki, K Ruetzler, CA Hallenbeck, JM AF Nawashiro, H Tasaki, K Ruetzler, CA Hallenbeck, JM TI TNF-alpha pretreatment induces protective effects against focal cerebral ischemia in mice SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE brain infarction; ischemic tolerance; leukocyte; microglia; tumor necrosis factor ID TUMOR-NECROSIS-FACTOR; MANGANESE-SUPEROXIDE-DISMUTASE; CEREBROSPINAL-FLUID; GERBIL HIPPOCAMPUS; INFARCT VOLUME; NITRIC-OXIDE; BRAIN; LIPOPOLYSACCHARIDE; RATS; EXPRESSION AB Cytokines are recognized to play an important role in acute stroke. Tumor necrosis factor-alpha (TNF) is one of the pro-inflammatory cytokines and is expressed in ischemic brain. We hypothesized that TNF might play a role in the regulation of tolerance to ischemia when administered prior to the ischemic episode. We studied the effects of pretreatment of TNF administered intravenously, intraperitoneally, or intracisternally in mice that were subjected to middle cerebral artery occlusion (MCAO) 48 h later. MCAO was performed in BALB/C mice by direct cauterization of distal MCA, which resulted in pure cortical infarction. A significant reduction in infarct size was noted in mice pretreated by TNF at the dose of 0.5 mu g/mouse (p < 0.01) intracisternally. At the doses used in this study, administration of TNF by intravenous or intraperitoneal routes was not effective. Immunohistochemical analysis of brains subjected to 24 h of MCAO revealed a significant decrease in CD11b immunoreactivity after TNF pretreatment compared with control MCAO. Preconditioning with TNF affects infarct size in a time- and dose-dependent manner. TNF induces significant protection against ischemic brain injury and is likely to be involved in the signaling pathways that regulate ischemic tolerance. RP Nawashiro, H (reprint author), NINCDS,STROKE BRANCH,NIH,36 CONVENT DR,MSC4128,BLDG 36,RM 4A03,BETHESDA,MD 20892, USA. NR 37 TC 266 Z9 282 U1 0 U2 6 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAY PY 1997 VL 17 IS 5 BP 483 EP 490 PG 8 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA XC697 UT WOS:A1997XC69700001 PM 9183285 ER PT J AU Vgontzas, AN Papanicolaou, DA Bixler, EO Kales, A Tyson, K Chrousos, GP AF Vgontzas, AN Papanicolaou, DA Bixler, EO Kales, A Tyson, K Chrousos, GP TI Elevation of plasma cytokines in disorders of excessive daytime sleepiness: Role of sleep disturbance and obesity SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID NECROSIS-FACTOR-ALPHA; HEALTHY-MEN; INTERLEUKIN-6; HUMANS; APNEA AB Excessive daytime sleepiness (EDS) and fatigue are frequent symptoms in the general population and the chief complaint of the majority of patients at Sleep Disorders Centers. There is evidence that the inflammatory cytokines tumor necrosis factor-alpha (TNF alpha), interleukin-1 beta (IL-1 beta), and IL-6 are involved in physiological sleep regulation and that their administration to humans is associated with sleepiness and fatigue. To explore whether plasma levels of TNF alpha, IL-1 beta, and IL-6 are elevated in patients with EDS, we measured morning plasma levels of TNF alpha, IL-1 beta, and IL-6 in 12 sleep apneics, 11 narcoleptics, 8 idiopathic hypersomniacs, and 10 normal controls. TNF alpha was significantly elevated in sleep apneics and narcoleptics compared to that in normal controls (P = 0.001 and P = 0.001, respectively). Plasma IL-1 beta concentrations were not different between sleep disorder patients and controls, whereas IL-6 was markedly and significantly elevated in sleep apneics compared to that in normal controls (P = 0.028). The primary factor influencing TNF alpha values was the degree of nocturnal sleep disturbance, whereas the primary determinant for IL-6 levels was the body mass index. Our findings suggest that TNF alpha and IL-6 might play a significant role in mediating sleepiness and fatigue in disorders of EDS in humans. C1 NICHHD, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. RP Vgontzas, AN (reprint author), PENN STATE UNIV, DEPT PSYCHIAT, SLEEP RES & TREATMENT CTR, 500 UNIV DR, HERSHEY, PA 17033 USA. NR 22 TC 554 Z9 583 U1 2 U2 12 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1997 VL 82 IS 5 BP 1313 EP 1316 DI 10.1210/jc.82.5.1313 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WX551 UT WOS:A1997WX55100002 PM 9141509 ER PT J AU Latronico, AC Chrousos, GP AF Latronico, AC Chrousos, GP TI Extensive personal, experience - Adrenocortical tumors SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ADRENAL-CORTICAL CARCINOMA; ACTIVATING MUTATIONS; ONCOGENIC MUTATIONS; NO EVIDENCE; G-PROTEIN; NEOPLASMS; GENE; RECEPTOR; OVEREXPRESSION; CISPLATIN C1 NICHHD, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. OI Latronico Xavier, Ana Claudia/0000-0001-6782-693X NR 50 TC 134 Z9 143 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1997 VL 82 IS 5 BP 1317 EP 1324 DI 10.1210/jc.82.5.1317 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WX551 UT WOS:A1997WX55100003 PM 9141510 ER PT J AU Dong, QH Debelenko, LV Chandrasekharappa, SC EmmertBuck, MR Zhuang, ZP Guru, SC Manickam, P Skarulis, M Lubensky, IA Liotta, LA Collins, FS Marx, SJ Spiegel, AM AF Dong, QH Debelenko, LV Chandrasekharappa, SC EmmertBuck, MR Zhuang, ZP Guru, SC Manickam, P Skarulis, M Lubensky, IA Liotta, LA Collins, FS Marx, SJ Spiegel, AM TI Loss of heterozygosity at 11q13: Analysis of pituitary tumors, lung carcinoids, lipomas, and other uncommon tumors in subjects with familial multiple endocrine neoplasia type 1 SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PARATHYROID TUMORS; ALLELIC LOSS; CHROMOSOME-11; GENE; HUMAN-CHROMOSOME-11; ASSOCIATION; HEREDITARY; MARKERS; PATIENT; REGION AB Loss of heterozygosity (LOH) for polymorphic markers flanking the multiple endocrine neoplasia type 1 (MEN-1) gene in parathyroid and pancreatic islet tumors from subjects with familial MEN-1 (FMEN-1) has been well documented and has led to the hypothesis that the MEN-1 gene functions as a tumor suppressor. To assess the role of the MEN-1 gene in the pathogenesis of tumors less commonly associated with MEN-1, we employed a large number of highly informative polymorphic markers closely Licked to the MEN-1 gene to study a series of 13 such tumors from subjects with FMEN-1 for LOH at 11q13. We were able to identify LOH for 1 or more 11q13 markers in 2 of 3 pituitary tumors, 3 lung carcinoids, and 1 of 2 lipomas. In every case studied, the allele lost represented the normal allele inherited from the unaffected parent. No LOH was detected in 3 skin angiofibromas, an esophageal leiomyoma, or a renal angiomyolipoma despite the presence of at least 2 informative markers for each tumor. Our results suggest that, like that for parathyroid and pancreatic islet tumors, the pathogenesis of pituitary tumors, lung carcinoids, and lipomas occurring in subjects with FMEN-1 probably involves loss of the normal tumor suppressor function of the MEN-1 gene. Our inability to detect 11q13 LOH in skin angiofibromas, leiomyoma, and angiomyolipoma from subjects with FMEN-1 is consistent with the possibility that these neoplasms arose independently by a mechanism unrelated to the MEN-1 gene, but a role for the MEN-1 gene in the pathogenesis of these tumors cannot be definitively excluded until the gene itself is identified and evaluated for small intragenic deletions or point mutations in such tumors. C1 NIDDKD, METAB DIS BRANCH, NIH, BETHESDA, MD 20892 USA. NCI, PATHOL LAB, NIH, BETHESDA, MD 20892 USA. NIHGR, LAB GENE TRANSFER, NIH, BETHESDA, MD 20892 USA. NR 32 TC 97 Z9 98 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1997 VL 82 IS 5 BP 1416 EP 1420 DI 10.1210/jc.82.5.1416 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WX551 UT WOS:A1997WX55100019 PM 9141526 ER PT J AU Espeland, MA Stefanick, ML KritzSilverstein, D Fineberg, SE Waclawiw, MA James, MK Greendale, GA AF Espeland, MA Stefanick, ML KritzSilverstein, D Fineberg, SE Waclawiw, MA James, MK Greendale, GA TI Effect of postmenopausal hormone therapy on body weight and waist and hip girths SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MIDDLE-AGED WOMEN; REPLACEMENT THERAPY; CIGARETTE-SMOKING; FAT DISTRIBUTION; RISK-FACTORS; PEPI TRIAL; MENOPAUSE; DISEASE; ASSOCIATIONS; ESTROGENS AB Reports from cross-sectional comparisons, nonrandomized prospective studies, and relatively small clinical trials indicate that postmenopausal hormone therapy may slightly decrease the amount of weight typically gained by women during the decade following menopause. Despite this, widespread belief remains that hormone therapy may cause weight gain. We use data from the Postmenopausal Estrogen/Progestin Interventions trial to characterize the impact of postmenopausal hormone therapy on weight and fat distribution and to examine the consistency of this impact among subgroups of women defined by lifestyle, clinical, and demographic factors. The Postmenopausal Estrogen/Progestin Interventions trial:was a 3-yr, placebo-controlled, randomized clinical trial of 875 women assessing the effects on cardiovascular risk factors of four hormone regimens: oral conjugated equine estrogen (GEE) therapy (0.625 mg daily alone), CEE in combination with medroxyprogesterone acetate (2.5 mg daily), CEE in combination with medroxyprogesterone acetate (10 mg daily on days 1-12), and CEE in combination with micronized progesterone (200 mg daily on days 1-12). Women randomly assigned to CEE with or without a progestational agent averaged 1.0 kg less weight gain at the end of 3 yr (P = 0.006) than those assigned to placebo. Assignment to CEE was also associated with averages of 1.2 cm less increase in waist girth (P = 0.01) and 0.3 cm less increase in hip (P = 0.07) girth. In regression models that included weight change as a covariate, none of these differences reached statistical significance. There were no significant differences in weight or girth changes among any of the four active hormone regimens. After accounting for the effects of assignment to active hormone therapy and baseline weight, older age (P = 0.008) and higher physical activity level at baseline (P = 0.002) were also independently predictive of less weight gain. The impact of hormone therapy on weight gain was similar among subgroups, except for those defined by baseline smoking status (P = 0.04) and physical activity level at home (P = 0.02). Factors that were independently associated with smaller increases in girths were: for waist, greater overall activity (P = 0.005) and Hispanic ethnicity (P = 0.02); and far hip, work activity (P = 0.003) and greater alcohol consumption (P = 0.03). None of these factors significantly affected the observed overall relationships between estrogen and changes in girth. C1 STANFORD UNIV, PALO ALTO, CA 94304 USA. UNIV CALIF SAN DIEGO, LA JOLLA, CA 92093 USA. INDIANA UNIV, SCH MED, INDIANAPOLIS, IN 46202 USA. UNIV CALIF LOS ANGELES, LOS ANGELES, CA 90024 USA. NHLBI, BETHESDA, MD 20892 USA. RP Espeland, MA (reprint author), WAKE FOREST UNIV, BOWMAN GRAY SCH MED, BIOSTAT SECT, MED CTR BLVD, WINSTON SALEM, NC 27157 USA. FU NHLBI NIH HHS [U01-HL40154, U01-HL40185, U01-HL40195] NR 48 TC 155 Z9 158 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1997 VL 82 IS 5 BP 1549 EP 1556 DI 10.1210/jc.82.5.1549 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WX551 UT WOS:A1997WX55100041 PM 9141548 ER PT J AU Prussin, C AF Prussin, C TI Cytokine flow cytometry: Understanding cytokine biology at the single-cell level SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Review DE interleukin-4; flow cytometry; cytokines; methods; T lymphocyte ID INTERFERON-GAMMA; T-CELLS; HETEROGENEITY; SUBPOPULATION; LYMPHOCYTES; T-HELPER-1 AB In the past 4 years, cytokine Row cytometry has emerged as the premier technique for enumeration of cytokine producing T cells. The multiparameter capability of flow cytometry permits the simultaneous detection of two or more cytokines within a single cell, allowing true Th1 vs. Th2 determination. The high throughput inherent to flow cytometry has enormous advantages when applied to clinical research questions previously not amenable for study using labor intensive techniques such as ELISPOT, limiting dilution and T cell cloning. Furthermore, cytokine flow cytometry allows the study of individual T cells directly ex vivo, minimizing artifacts due to long term culture. As such, cytokine flow yields unique insights into cytokine biology heretofore not possible. We have used cytokine flow cytometry to examine coexpression of cytokines within the memory/effector CD4+, CD27- subset. Doing so, we have found distinct cytokine producing subsets that correlate with the previously described Th1, Th2 and Th0 subsets. The majority of cytokine producing cells were of these first two subsets with fewer cells coexpressing IFN-gamma and IL-4. These results validate the Th1/Th2 hypothesis and demonstrate specific subsets of cytokine producing T cells in fresh ex vivo human T cells. RP Prussin, C (reprint author), NIAID,LAB ALLERG DIS,NIH,10 CTR DR,MSC-1881,BETHESDA,MD 20892, USA. OI Prussin, Calman/0000-0002-3917-3326 NR 28 TC 105 Z9 107 U1 0 U2 4 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD MAY PY 1997 VL 17 IS 3 BP 195 EP 204 DI 10.1023/A:1027350226435 PG 10 WC Immunology SC Immunology GA XA037 UT WOS:A1997XA03700001 PM 9168399 ER PT J AU Kol, S BenShlomo, I Ruutiainen, K Ando, M DaviesHill, TM Rohan, RM Simpson, IA Adashi, EY AF Kol, S BenShlomo, I Ruutiainen, K Ando, M DaviesHill, TM Rohan, RM Simpson, IA Adashi, EY TI The midcycle increase in ovarian glucose uptake is associated with enhanced expression of glucose transporter 3 - Possible role for interleukin-1, a putative intermediary in the ovulatory process SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE ovary; IL-1; glucose transporter; ovulation ID CELL-CELL INTERACTION; RAT OVARY; RECEPTOR ANTAGONIST; MEDIATED REGULATION; GENE-EXPRESSION; NITRIC-OXIDE; PROSTAGLANDIN PRODUCTION; TISSUE DISTRIBUTION; LUTEAL CELLS; BRAIN AB This study characterizes the rat ovary as a site of hormonally dependent glucose transporter (Glut) expression, and explores the potential role of interleukin (IL)-1, a putative intermediary in the ovulatory process, in this regard, Molecular probing throughout a simulated estrous cycle revealed a significant surge in ovarian Glut3 (but not Glut1) expression at the time of ovulation, Treatment of cultured whole ovarian dispersates from immature rats with IL-1 beta resulted in upregulation of the relative abundance of the Glut1 (4.5-fold) and Glut3 (3.5-fold) proteins as determined by Western blot analysis. Other members of the Glut family (i.e., Gluts 2, 4, and 5) remained undetectable, The ability of IL-1 to upregulate Glut1 and Glut3 transcripts proved time-, dose-, nitric oxide-, and protein biosynthesis-dependent but glucose independent. Other ovarian agonists (i.e., TNF alpha, IGF-I, interferon-gamma, and insulin) were without effect. Taken together, our findings establish the mammalian ovary as a site of cyclically determined Glut1 and Glut3 expression, and disclose the ability of IL-1 to induce the ovarian expression as well as translation of Glut1 and Glut3 (but not of Gluts 2, 4, or 5). Our observations also establish IL-1 as the first known regulator of Glut3, the most efficient Glut known to date. In so doing, IL-1, a putative component of the ovulatory process, may be acting to meet the increased metabolic demands imposed on the growing follicle and the ovulated cumulus-enclosed oocyte. C1 UNIV MARYLAND,SCH MED,DEPT OBSTET & GYNECOL,DIV REPROD ENDOCRINOL,BALTIMORE,MD 21201. NIDDKD,EXPT DIABET METAB & NUTR SECT,BETHESDA,MD 20892. FU NICHD NIH HHS [HD-30288, HD-19998] NR 42 TC 41 Z9 42 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY 1 PY 1997 VL 99 IS 9 BP 2274 EP 2283 DI 10.1172/JCI119403 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA WY013 UT WOS:A1997WY01300030 PM 9151802 ER PT J AU Thomas, DL Yarbough, PO Vlahov, D Tsarev, SA Nelson, KE Saah, AJ Purcell, RH AF Thomas, DL Yarbough, PO Vlahov, D Tsarev, SA Nelson, KE Saah, AJ Purcell, RH TI Seroreactivity to hepatitis E virus in areas where the disease is not endemic SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HOMOSEXUAL MEN; DRUG-USERS; C VIRUS; INFECTION; ANTIBODY AB If the occurrence of hepatitis E virus antibody (anti-HEV) in regions where the disease is not endemic represents infection, rates mag be greater in high-risk populations and behavioral correlates may reflect recognized transmission modes, Serum samples from 300 homosexual males, 300 injection drug users (IDUs), and 300 blood donors from Baltimore, Md,, were tested for anti-HEV by enzyme immunoassay. Anti-HEV was found in an unexpectedly high percentage of homosexual men (15.9%) and IDUs (23.0%), However, anti-HEV was present in a similar proportion of blood donors (21.3%) (P > 0.05), while hepatitis A, B, and C virus antibodies were more prevalent in the high-risk groups (P < 0.001). Among homosexual men, anti-HEV was not significantly correlated with a history of hepatitis, high-risk sexual practices, or sexually transmitted infections, in contrast to hepatitis A and B antibodies, Among IDUs, anti-HEV was not significantly associated with a history of hepatitis or high-risk drug-using practices, as was found with hepatitis C antibodies, In a setting without endemic hepatitis E disease, there was no evidence that anti-HEV reflected subclinical infection, Until the basis for HEV seroreactivity in such areas is elucidated, anti-HEV results should be interpreted with caution. C1 JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD. GENELABS TECHNOL INC,REDWOOD CITY,CA. NIAID,HEPATITIS VIRUSES SECT,INFECT DIS LAB,NIH,BETHESDA,MD 20892. FU NIAID NIH HHS [U01-AI-35042]; NIDA NIH HHS [DA-04334, DA-08004] NR 15 TC 170 Z9 176 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 MAY PY 1997 VL 35 IS 5 BP 1244 EP 1247 PG 4 WC Microbiology SC Microbiology GA WV178 UT WOS:A1997WV17800038 PM 9114415 ER PT J AU Fedorko, DP Williams, EC AF Fedorko, DP Williams, EC TI Use of cycloserine-cefoxitin-fructose agar and L-proline-aminopeptidase (PRO Discs) in the rapid identification of Clostridium difficile SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID MEDIA AB The PRO Disc (Carr-Scarborough Microbiologicals, Inc., Decatur, Ga.) can be used to screen for L-proline-aminopeptidase produced by Clostridium difficile grown on cycloserine-cefoxitin-fructose agar (CCFA). Fifty stored isolates of C. difficile (48 toxin-positive and 2 toxin-negative isolates) and 47 fresh C. difficile isolates (39 toxin-positive and 8 toxin-negative isolates) were all PRO Disc positive, Other Clostridium species that were PRO Disc positive could be differentiated from C. difficile by failure to grow on CCFA, different colonial morphology on CCFA, or morphology upon Gram staining. RP Fedorko, DP (reprint author), MICROBIOL SERV,DEPT CLIN PATHOL,WARREN GRANT MAGNUSON CLIN CTR,NIH,BLDG 10,ROOM 2C-385,BETHESDA,MD 20892, USA. NR 10 TC 48 Z9 48 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 MAY PY 1997 VL 35 IS 5 BP 1258 EP 1259 PG 2 WC Microbiology SC Microbiology GA WV178 UT WOS:A1997WV17800042 PM 9114419 ER PT J AU Pestalozzi, BC Peterson, HF Gelber, RD Goldhirsch, A Gusterson, BA Trihia, H Lindtner, J CortesFunes, H Simmoncini, E Byrne, MJ Golouh, R Rudenstam, CM CastiglioneGertsch, M Allegra, CJ Johnston, PG AF Pestalozzi, BC Peterson, HF Gelber, RD Goldhirsch, A Gusterson, BA Trihia, H Lindtner, J CortesFunes, H Simmoncini, E Byrne, MJ Golouh, R Rudenstam, CM CastiglioneGertsch, M Allegra, CJ Johnston, PG TI Prognostic importance of thymidylate synthase expression in early breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GENE-EXPRESSION; CELLS; 5-FLUOROURACIL; SYNTHETASE; CHEMOTHERAPY; QUANTITATION; INTERFERON; COMPLEX; TUMORS; GAMMA AB Purpose: To assess the prognostic importance of thymidylate synthase (TS) expression in breast tumors of patients with early-stage breast cancer, and to determine whether the benefit of chemotherapy (CT) is associated with TS expression. Patients and Methods: The level of TS expression was evaluated in 210 negative and 278 node-positive patients enrolled onto Trial V of the international Breast Cancer Study Group ([IBCSG] formerly the Ludwig Breast Cancer Study Group) with a median follow-up time of 8.5 years. TS expression was assessed using the immunohistochemical method with the monoclonal antibody TS 106 on paraffin-embedded tissue specimens. Results: High TS expression was associated with a significantly worse prognosis in node-positive but not in node-negative breast cancer patients. Twenty-seven percent of node-positive patients with high TS expression were disease-free at 10 years, compared with 44% of node-positive patients with low TS expression (P=.03). Forty-one percent of patients with node-positive high-TS-expressing tumors were alive after 10 years, compared with 49% of those with low TS expression (P=.06). The association between TS and disease-free survival (DFS) and overall survival (OS) wets independent of other prognostic factors such as tumor size, tumor grade, nodal status, vessel invasion, estrogen receptor (ER)/progestin receptor (PR) status, c-erb 8-2, or Ki-67 expression. In node-positive patients, six cycles of standard adjuvant cyclophosphamide, methotrexate, and fluorouracil ([5-FU] CMF) CT improved DFS and OS compared with one cycle of perioperative CMF therapy. The magnitude of this benefit was greatest in patients whose tumors had high TS expression (P <.01 for DFS; P <.01 for OS). Node-negative patients demonstrated no difference in outcome to CT based on TS expression; however, the power to detect differences was limited by the small number of events in this group. Conclusion: In early-stage breast cancer, high TS expression is associated with a significantly worse prognosis in node-positive patients. Node-positive patients with high TS levels demonstrate the most significant improvement in DFS and OS when treated with six cycles of conventional adjuvant CMF therapy. C1 INT BREAST CANC STUDY GRP,BERN,SWITZERLAND. NCI,NAVY MED ONCOL BRANCH,DIV CLIN SCI,BETHESDA,MD 20892. RI gusterson, barry/D-3752-2009 NR 31 TC 105 Z9 106 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1997 VL 15 IS 5 BP 1923 EP 1931 PG 9 WC Oncology SC Oncology GA WZ564 UT WOS:A1997WZ56400029 PM 9164203 ER PT J AU Kohn, EC Figg, WD Sarosy, GA Bauer, KS Davis, PA Soltis, MJ Thompkins, A Liotta, LA Reed, E AF Kohn, EC Figg, WD Sarosy, GA Bauer, KS Davis, PA Soltis, MJ Thompkins, A Liotta, LA Reed, E TI Phase I trial of micronized formulation carboxyamidotriazole in patients with refractory solid tumors: Pharmacokinetics, clinical outcome, and comparison of formulations SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SIGNAL-TRANSDUCTION; CALCIUM INFLUX; CANCER; INHIBITION; L651582 AB Purpose: Cytostatic agents targeted against angiogenesis and tumor cell invasive potential form a new class of investigational drugs. Orally administered carboxyamidotriazole (CAI) (NSC609974) is both antiangiogenic and antimetastatic. An encapsulated micronized powder formulation has been developed to optimize CAI administration. A phase I dose escalation trial with pharmacokinetic analysis has been performed, Patients and Methods: Twenty-one patients with refractory solid tumors and good end organ function and performance status were enrolled onto the study. Patients received a test dose followed 1 week later by daily administration of CAI in the encapsulated micronized formulation at doses of 100 to 350 mg/m(2). Patients remained on CAI until disease progression or dose-limiting toxicity. Plasma samples were taken to characterize the pharmacokinetic parameters of this formulation of CAI. Results: All patients were assessable for toxicity and 18 were assessable for pharmacokinetics and response analysis, Grade 1 and 2 gastrointestinal side effects were observed in up to 50% of patients. Dose-limiting toxicity was observed in both patients treated at 350 mg/m(2)/d, consisting of reversible grade 2 to 3 cerebellar ataxia (n = 1) and confusion (n = 1). One minor response (MR) was observed in a patient with renal cell carcinoma and another nine patients held disease stabilization (MR + SD = 47%). Pharmacokinetic analysis demonstrated reduced bioavailability (58% reduction) compared with the PEG-400 liquid formulation previously reported. Conclusion: The better toxicity profile of encapsulated micronized CAI with similar frequency of disease stabilization and ease of administration compared with the liquid or gelatin capsule, suggests that the micronized formulation is a preferable formulation for subsequent studies. A dose of 300 mg/m(2)/d is proposed for phase II investigations. (C) 1997 by American Society of Clinical Oncology. C1 NCI,LAB PATHOL & CLIN PHARMACOL,BETHESDA,MD 20892. RI Figg Sr, William/M-2411-2016 NR 22 TC 52 Z9 53 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1997 VL 15 IS 5 BP 1985 EP 1993 PG 9 WC Oncology SC Oncology GA WZ564 UT WOS:A1997WZ56400036 PM 9164210 ER PT J AU Widemann, BC Balis, FM Murphy, RF Sorensen, JM Montello, MJ OBrien, M Adamson, PC AF Widemann, BC Balis, FM Murphy, RF Sorensen, JM Montello, MJ OBrien, M Adamson, PC TI Carboxypeptidase-G(2), thymidine, and leucovorin rescue in cancer patients with methotrexate-induced renal dysfunction SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HIGH-DOSE METHOTREXATE; SEQUENTIAL HEMODIALYSIS; RHESUS-MONKEYS; CLINICAL USE; TOXICITY; HEMOPERFUSION; PHARMACOLOGY; ELIMINATION; IMPAIRMENT; METABOLITE AB Purpose: Methotrexate nephrotoxicity can lead to delayed methotrexate elimination and the development of life-threatening toxicity, which may not be preventable with the standard rescue agent leucovorin. In preclinical studies, we previously demonstrated that carboxypeptidase-G(2) (CPDG(2)) rapidly hydrolyzes methotrexate to nontoxic metabolites. A protocol for the compassionate use of CPDG(2) in patients who develop nephrotoxicity while receiving high-dose methotrexate was therefore developed. The pharmacologic and clinical outcome of CPDG(2) rescue administered with thymidine and leucovorin in 20 patients is presented here. Methods: Patients with high-dose methotrexote-induced renal dysfunction received one to three doses of CPDG(2), 50 U/kg body weight intravenously (IV), thymidine 8 g/m(2)/d by continuous IV infusion, and standard pharmacokinetically guided leucovorin rescue. Plasma concentrations of methotrexate and its inactive metabolite 4-deoxy-4-amino-N-10-methylpteroic acid (DAMPA) were measured before and after CPDG(2) using high-pressure liquid chromatography (HPLC). Tolerance of CPDG(2) and thymidine, development of methotrexate toxicities, and recovery of renal function were monitored. Results: Twenty patients who received high-dose methotrexate for osteosarcoma (n=11), lymphoid cancers (n=8), and gastric cancer (n=1) developed nephrotoxicity (median serum creatinine, 3.2 mg/dL) and elevated plasma methotrexate concentrations (median, 201 mu mol/L at hour 46). CPDG(2) and thymidine rescue was well tolerated and resulted in a rapid 95.6% to 99.6% reduction in the plasma methotrexate concentration. Methotrexate-related toxicity was mild to moderate. Serum creatinine returned to normal values at a median of 22 days. Conclusion: CPDG(2), thymidine,and leucovorin rescue was highly effective in 20 patients at high risk for developing life-threatening methotrexate toxicity after the onset of methotrexate-induced nephrotoxicity and delayed methotrexate excretion. (C) 1997 by American Society of Clinical Oncology. C1 NCI,CANC THERAPY EVALUAT PROGRAM,NIH,BETHESDA,MD 20892. RP Widemann, BC (reprint author), NCI,PEDIAT BRANCH,NIH,BLDG 10,ROOM 13N240,10 CTR DR MSC 1928,BETHESDA,MD 20892, USA. NR 39 TC 71 Z9 73 U1 1 U2 8 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1997 VL 15 IS 5 BP 2125 EP 2134 PG 10 WC Oncology SC Oncology GA WZ564 UT WOS:A1997WZ56400053 PM 9164227 ER PT J AU Premkumar, A Stratakis, CA Shawker, TH Papanicolaou, A Chrousos, GP AF Premkumar, A Stratakis, CA Shawker, TH Papanicolaou, A Chrousos, GP TI Testicular ultrasound in Carney complex: Report of three cases SO JOURNAL OF CLINICAL ULTRASOUND LA English DT Article ID ENDOCRINE OVERACTIVITY; SPOTTY PIGMENTATION; MYXOMAS C1 NICHHD,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. RP Premkumar, A (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,10 CTR DR,BETHESDA,MD 20892, USA. NR 7 TC 34 Z9 36 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0091-2751 J9 J CLIN ULTRASOUND JI J. Clin. Ultrasound PD MAY PY 1997 VL 25 IS 4 BP 211 EP 214 DI 10.1002/(SICI)1097-0096(199705)25:4<211::AID-JCU10>3.0.CO;2-N PG 4 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA WW919 UT WOS:A1997WW91900009 PM 9142622 ER PT J AU Burt, S Hutchins, C Zielinski, PJ AF Burt, S Hutchins, C Zielinski, PJ TI A Monte Carlo method for finding important ligand fragments from receptor data SO JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN LA English DT Article DE simulated annealing; rational ligand design; ligand design; structure-based ligand design ID FAVORABLE BINDING-SITES; DIRECTED DRUG DESIGN; HYDROGEN-BOND FUNCTIONS; AQUEOUS SOLVATION; FREE-ENERGIES; 3-DIMENSIONAL STRUCTURE; STRUCTURE GENERATION; AUTOMATED DOCKING; LEAD GENERATION; PROBE GROUPS AB A simulated annealing method for finding important ligand fragments is described. At a given temperature, ligand fragments are randomly selected and randomly placed within the given receptor cavity, often replacing or forming bonds with existing ligand fragments. For each new ligand fragment combination, the bonded, nonbonded, polarization and solvation energies of the new ligand-receptor system are compared to the previous configuration. Acceptance or rejection of the new system is decided using the Boltzmann distribution e(-E/kT), where E is the energy difference between the old and new systems, k is the Boltzmann constant and T is the temperature. Thus, energetically unfavorable fragment switches are sometimes accepted, sacrificing immediate energy gains in the interest of finding a system with minimum energy. By lowering the temperature, the rate of unfavorable switches decreases and energetically favorable combinations become more difficult to change. The process is terminated when the frequency of switches becomes too small. As a test, the method predicted positions and types of important ligand fragments for neuraminidase that were in accord with the known ligand, sialic acid. C1 NCI,FREDERICK,MD 21702. ABBOTT LABS,ABBOTT PK,IL 60064. NR 46 TC 1 Z9 1 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0920-654X J9 J COMPUT AID MOL DES JI J. Comput.-Aided Mol. Des. PD MAY PY 1997 VL 11 IS 3 BP 243 EP 255 DI 10.1023/A:1007952511172 PG 13 WC Biochemistry & Molecular Biology; Biophysics; Computer Science, Interdisciplinary Applications SC Biochemistry & Molecular Biology; Biophysics; Computer Science GA XQ324 UT WOS:A1997XQ32400003 PM 9263851 ER PT J AU Courcoutsakis, NA Langford, CA Sneller, MC Cupps, TR Gorman, K Patronas, NJ AF Courcoutsakis, NA Langford, CA Sneller, MC Cupps, TR Gorman, K Patronas, NJ TI Orbital involvement in Wegener granulomatosis: MR findings in 12 patients SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE orbits; magnetic resonance imaging; Wegener granulomatosis; lungs, disease; orbits, diseases ID PSEUDOTUMOR; MANIFESTATIONS; DIAGNOSIS AB Purpose: Our goal was to characterize the MR features of orbital Wegener granulomatosis (WG). Method: Twelve patients with pathologically proven WG were studied with MRI. Enhanced and unenhanced T1-weighted sequences with conventional and fat-suppressed techniques were used, T2-weighted images were also obtained, Signal intensity measurements were made in each orbital lesion on the T2-weighted images and compared with that of normal fat. The degree of enhancement was also evaluated by measuring the change in signal intensity or each lesion between the unenhanced and enhanced studies. Results: Seventeen orbital lesions were identified in the 12 patients. Fifteen of the lesions examined by T2-weighted sequences demonstrated a marked decrease in signal intensity. The unenhanced, non-far-suppressed T1-weighted sequences provided the best contrast between lesion and normal structures, All of the WG lesions enhanced, but the degree of enhancement varied. The enhancement characteristics were best appreciated on the fat-suppressed T1-weighted technique. Conclusion: MRI is an excellent imaging modality to evaluate orbital involvement in WG. A marked decrease in the T2 signal is a characteristic feature of this entity. The unenhanced, non-fat-suppressed T1-weighted sequence is the preferred method for lesion detection and for definition of the pattern of anatomic involvement when utilizing MRI. C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NIAID,BETHESDA,MD 20892. GEORGETOWN UNIV,DEPT MED,WASHINGTON,DC. NR 27 TC 18 Z9 19 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAY-JUN PY 1997 VL 21 IS 3 BP 452 EP 458 DI 10.1097/00004728-199705000-00021 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WV864 UT WOS:A1997WV86400021 PM 9135657 ER PT J AU Albandar, JM Brown, LJ Genco, RJ Loe, H AF Albandar, JM Brown, LJ Genco, RJ Loe, H TI Clinical criteria for the classification of early onset periodontitis SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR, BETHESDA, MD 20892 USA. SUNY BUFFALO, BUFFALO, NY USA. UNIV CONNECTICUT, STORRS, CT 06269 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAY PY 1997 VL 76 IS 5 BP 1097 EP 1097 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA WW075 UT WOS:A1997WW07501149 ER PT J AU Ruhl, S Sandberg, AL Cisar, JO AF Ruhl, S Sandberg, AL Cisar, JO TI Lectin-mediated binding of streptococci and Actinomyces to granulocyte glycoprotein receptors SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 UNIV REGENSBURG,DEPT OPERAT DENT & PERIODONTOL,D-8400 REGENSBURG,GERMANY. NIDR,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAY PY 1997 VL 76 IS 5 BP 1100 EP 1100 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA WW075 UT WOS:A1997WW07501172 ER PT J AU Skaleric, U Bogataj, L Pecnik, SL McCartneyFrancis, N Wahl, SM AF Skaleric, U Bogataj, L Pecnik, SL McCartneyFrancis, N Wahl, SM TI Nitric oxide in gingival fluid correlates with periodontal inflammation. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 UNIV DENT CLIN,LJUBLJANA,SLOVENIA. LI,NIDR,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAY PY 1997 VL 76 IS 5 BP 1147 EP 1147 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA WW075 UT WOS:A1997WW07501527 ER PT J AU Matsuki, Y Nakashima, M Amizuka, N Warshawsky, H Goltzman, D Yamada, K Krebsbach, P Lee, SK Kozak, C Yamada, Y AF Matsuki, Y Nakashima, M Amizuka, N Warshawsky, H Goltzman, D Yamada, K Krebsbach, P Lee, SK Kozak, C Yamada, Y TI A novel tooth-specific gene: Ameloblastin. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIIGATA UNIV,DEPT PERIO,NIIGATA,JAPAN. NIH,BETHESDA,MD 20892. MCGILL UNIV,MONTREAL,PQ H3A 2T5,CANADA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAY PY 1997 VL 76 IS 5 BP 1179 EP 1179 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA WW075 UT WOS:A1997WW07501761 ER PT J AU Aguilera, G Jessop, DS Harbuz, MS Kiss, A Lightman, SL AF Aguilera, G Jessop, DS Harbuz, MS Kiss, A Lightman, SL TI Differential regulation of hypothalamic pituitary corticotropin releasing hormone receptors during development of adjuvant-induced arthritis in the rat SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID CHRONIC INFLAMMATORY STRESS; MESSENGER-RNA EXPRESSION; FUNCTIONAL EXPRESSION; RIBONUCLEIC-ACID; ADRENAL AXIS; CRF RECEPTOR; HPA AXIS; BRAIN; GLUCOCORTICOIDS; VASOPRESSIN AB The expression of corticotropin releasing hormone (CRH) in the hypothalamic paraventricular nucleus (PVN) and CRH receptor mRNA in the PVN and anterior pituitary was studied during development of adjuvant-induced arthritis in Piebald-Viral-Glare rats, using in situ hybridization techniques. As previously shown with i.p. hypertonic saline injection, basal and immobilization stress-stimulated CRH mRNA levels in the PVN were significantly lower than ill controls 14 days after adjuvant injection. However, 7 days after injection, preceding the onset of inflammation, the increase of CRH mRNA following immobilization was significantly higher than in control rats, In contrast to other chronic stress paradigms, inflammation stress failed to induce type-1 CRH receptor (CRH-R1) mRNA in the PVN, either at 7 days, or at 14 days after adjuvant injection, when inflammation is present. The ability of acute immobilization to induce CRH-R1 mRNA in the PVN was not affected 14 days after adjuvant injection but parallel to the CRH peptide mRNA response it was markedly potentiated at 7 days, Pro-opiomelanocorpin (POMC) mRNA levels in the anterior pituitary increased significantly 14 days after adjuvant injection, and they were unaffected by Ih immobilization. While CRH binding in the pituitary decreased significantly 14 days after adjuvant injection, CRH-R1 mRNA was unchanged. This study biphasic hypothalamic responses to acute stress development of adjuvant-induced arthritis, with enhanced CRH peptide and CRH-R1 mRNAs responses at 7 days, preceding the onset of inflammation, and blunted CRH mRNA responses at 14 days at the height of the inflammatory response, The lack of CRH receptor expression in the PVN in this model of chronic inflammation stress associated to low hypothalamic CRH peptide levels supports the view that positive feedback regulation by CRH is necessary to maintain enhanced CRH expression during chronic stress. C1 UNIV BRISTOL, BRISTOL ROYAL INFIRM, DEPT MED, BRISTOL BS2 8HW, AVON, ENGLAND. RP Aguilera, G (reprint author), NICHHD, DEV ENDOCRINOL BRANCH,SECT ENDOCRINE PHYSIOL,NIH, BLDG 10,RM 10 N 262, 10 CTR DR, BETHESDA, MD 20892 USA. NR 40 TC 34 Z9 34 U1 0 U2 0 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD MAY PY 1997 VL 153 IS 2 BP 185 EP 191 DI 10.1677/joe.0.1530185 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WX627 UT WOS:A1997WX62700002 PM 9166107 ER PT J AU Aoyama, H Kato, H Dixon, D AF Aoyama, H Kato, H Dixon, D TI Specificity of antibodies against rodent transforming growth factor-alpha protein SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE TGF-alpha; anti-TGF-alpha antibody; immunohistochemistry; competition study; Western blotting; rats and mice ID ANHYDRASE-RICH CELLS; MOUSE UTERUS; PERIIMPLANTATION PERIOD; MONOCLONAL-ANTIBODIES; COLLECTING DUCT; RAT-KIDNEY; EXPRESSION; LOCALIZATION; SEQUENCE; CANCER AB We found that the immunohistochemical distribution of TGF-alpha varied in rodent tissues depending on the antibody used, suggesting that the specificity of anti-TCF-alpha antibodies differs significantly. To address this issue, we compared the specificity of two representative antibodies that have been widely used to detect rodent TGF-alpha. In a competition study, the antibodies were preincubated with an excess of synthetic rat TGF-alpha(34-50) and were used for staining of rat and mouse kidneys and/or uterus. The results revealed that one of the antibodies, anti-rat TGF-alpha polyclonal antibody, was neutralized by the peptide, whereas the other, anti-human TGF-alpha monoclonal antibody, was not absorbed by the peptide up to an excess of 100-fold. Western blotting analysis showed that the anti-rat TGF-alpha polyclonal antibody recognized both human and rat purified TCF-alpha. However, the antihuman TGF-alpha monoclonal antibody did not detect purified rat TGF-alpha, although the antibody reacted with mouse proteins other than TGF-alpha from kidneys and uterus, purified human TGF-alpha, and mouse carbonic anhydrase II. These data indicate that the anti-human TGF-alpha monoclonal antibody does not recognize rodent TGF-alpha. under our experimental conditions and suggest that distribution of TGF-alpha in rodent tissues may need to be reexamined. C1 NIEHS,LAB EXPT PATHOL,RES TRIANGLE PK,NC 27709. KYUSHU UNIV,MED INST BIOREGULAT,DEPT REPROD PHYSIOL & ENDOCRINOL,BEPPU,OITA,JAPAN. NR 26 TC 6 Z9 6 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD MAY PY 1997 VL 45 IS 5 BP 695 EP 701 PG 7 WC Cell Biology SC Cell Biology GA WY343 UT WOS:A1997WY34300007 PM 9154156 ER PT J AU Winter, CC Long, EO AF Winter, CC Long, EO TI A single amino acid in the p58 killer cell inhibitory receptor controls the ability of natural killer cells to discriminate between the two groups of HLA-C allotypes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID B MOLECULES; NK CLONES; RECOGNITION; SUBSET; LYSIS AB To examine the structural basis for the specific recognition of the MHC class I allotypes HLA-Cw*0401 and HLA-Cw*0304 by the killer cell inhibitory receptors (KIR) cl42 and cl43, respectively, mutant KIR-Ig fusion proteins were tested by direct binding to cells transfected with single HLA-C alleles. The putative loop region at position 44-46 of KIR contained amino acids that were necessary for the discrimination between HLA-Cw*0401 and HLA-Cw*0304. Surprisingly, exchanging the methionine at position 44 in cl42 with the lysine at position 44 in cl43 was sufficient to switch the specificity of cl42 from HLA-Cw*0401 to HLA-Cw*0304, and vice versa. Thus, a single amino acid in the first Ig domain of these KIR determines their ability to discriminate between the two groups of HLA-C allotypes. RP Winter, CC (reprint author), NIAID,LIG,NIH,TWINBROOK 2,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 16 TC 152 Z9 154 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1997 VL 158 IS 9 BP 4026 EP 4028 PG 3 WC Immunology SC Immunology GA WV761 UT WOS:A1997WV76100002 PM 9126959 ER PT J AU Giordano, V DeFalco, G Chiari, R Quinto, I Pelicci, PG Bartholomew, L Delmastro, P Gadina, M Scala, G AF Giordano, V DeFalco, G Chiari, R Quinto, I Pelicci, PG Bartholomew, L Delmastro, P Gadina, M Scala, G TI Shc mediates IL-6 signaling by interacting with gp130 and Jak2 kinase SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERLEUKIN-6 GENE; CYTOKINE RECEPTORS; TYROSINE KINASE; EXPRESSION; PROTEIN; TRANSDUCTION; ASSOCIATION; ACTIVATION; RAS; CELLS AB IL-6 is a multifunctional cytokine involved in hemopoiesis, immune regulation, inflammation, neural development, and infection. IL-6 belongs to a family of related cytokines that includes leukemia inhibitory factor, oncostatin M, IL-11, ciliary neurotropic factor, and cardiotropin-1, all of which initiate signaling through a receptor-associated gp130. IL-6 induces homodimerization of gp130 and activates the Jak/STAT pathway of signal transduction. In addition, IL-6 stimulates the mitogen-activated protein kinases designated ERK (extracellular signal-regulated kinase)-1 and -2. Activation of ERK-1 and -2 may involve the Src homology-2 containing proteins Shc and Grb2. Here we provide evidence that Shc could function as signaling molecules for IL-6 in DeFew-IL-6R/gp130 cells, a human B lymphoma cell line engineered to express high levels of both the IL-6R (p80) and the gp130 subunit. IL-6 was shown to promote the rapid tyrosine phosphorylation of gp130, Jak2, and Shc proteins. Moreover, Shc associated both in vivo and in vitro with phosphorylated gp130 through the Shc-Src homology-2 domain. We also report that Shc bound to activated Jak2 by using the Shc amino terminal phosphotyrosine interaction domain. Following IL-6 stimulation, Shc physically associated with Grb2. Thus, the data point to Shc proteins as a functional link between the Jak2 and Ras pathways of IL-6 signal transduction. C1 UNIV NAPLES FEDERICO II,SCH MED,DEPT BIOCHEM & BIOMED TECHNOL,I-80131 NAPLES,ITALY. UNIV PERUGIA,MOL BIOL LAB,INST CLIN MED,I-06100 PERUGIA,ITALY. UNIV REGGIO CALABRIA,DEPT CLIN & EXPT MED,CATANZARO,ITALY. MOL BIOL RES INST,DEPT IMMUNOL,POMEZIA,ITALY. EUROPEAN INST ONCOL,MILAN,ITALY. NIAMSD,LYMPHOCYTE CELL BIOL SECT,NIH,BETHESDA,MD 20892. RI SCALA, GIUSEPPE/A-3280-2009 NR 41 TC 45 Z9 46 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1997 VL 158 IS 9 BP 4097 EP 4103 PG 7 WC Immunology SC Immunology GA WV761 UT WOS:A1997WV76100011 PM 9126968 ER PT J AU Kozhich, AT Caspi, RR Berzofsky, JA Gery, I AF Kozhich, AT Caspi, RR Berzofsky, JA Gery, I TI Immunogenicity and immunopathogenicity of an autoimmune epitope are potentiated by increasing MHC binding through residue substitution SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CLASS-II MOLECULES; PROTEIN IRBP; DETERMINANT; PEPTIDES; ANTIGEN; INDUCTION; IMMUNODOMINANT; UVEORETINITIS; RESPONSES; UVEITIS AB We have previously shown that in Lewis rats, peptide 273-283 (TWECSGVLPCV) of rat interphotoreceptor retinoid-binding protein (IRBP) serves as a ''surrogate'' epitope for pathogenic lymphocytes sensitized against peptide 1181-1191 (SWECVGV VPDV) of bovine IRBP, Yet, peptide 273-283 itself causes experimental autoimmune uveoretinitis (EAU) only at 200 nmol/rat, whereas peptide 1181-1191 is pathogenic even at 0.2 nmol. This difference was attributed to the higher affinity of 1181-1191 to MHC molecules. Here we demonstrate that substitution of putative MHC binding-residues of peptide 273-283 with the corresponding ones of 1181-1191 results in increased binding to MHC and in remarkably elevated immunologic capacities. Analogs of 273-283 were synthesized, in which residues 277 and 282 were substituted with one or both the corresponding amino acids of peptide 1181-1191, V and D, respectively. The main findings were: 1) substitutions drastically increased MHC affinity, namely, 273-283(V277,D282) >> 273-283(D283) >>> 273-283; 2) the substituted analogs were much more immunogenic than the native peptide, inducing cellular responses at much lower doses; 3) the analogs were more antigenic in vitro than the native peptide; 4) the analogs were exceedingly pathogenic; peptide 273-283(V277,D282) caused disease even at 0.02 nmol/rat; and 5) the analogs were superior to the native peptide in their capacity to stimulate production of IFN-gamma by sensitized lymphocytes, Thus, enhancement of affinity of an autoimmune peptide for MHC molecules increases both immunogenicity and pathogenicity. C1 NEI,IMMUNOL LAB,BETHESDA,MD 20892. NCI,METAB BRANCH,NATL INST HLTH,BETHESDA,MD 20892. NR 40 TC 16 Z9 16 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1997 VL 158 IS 9 BP 4145 EP 4151 PG 7 WC Immunology SC Immunology GA WV761 UT WOS:A1997WV76100017 PM 9126974 ER PT J AU Marincola, FM AF Marincola, FM TI Commentary. The multiple ways to tumor tolerance SO JOURNAL OF IMMUNOTHERAPY LA English DT Editorial Material ID CYTOLYTIC T-LYMPHOCYTES; MELANOMA ANTIGEN GP100; IN-VITRO; INFILTRATING LYMPHOCYTES; HLA-A2 MELANOMAS; PERIPHERAL-BLOOD; EPITOPES; CELLS; IDENTIFICATION; RECOGNITION RP Marincola, FM (reprint author), NCI,SURG BRANCH,DEPT SURG,DEPT TRANSFUS MED,CLIN CTR,NIH,BLDG 10,ROOM 2B56,BETHESDA,MD 20892, USA. NR 16 TC 5 Z9 6 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAY PY 1997 VL 20 IS 3 BP 178 EP 179 DI 10.1097/00002371-199705000-00002 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA XA886 UT WOS:A1997XA88600002 PM 9181455 ER PT J AU Miele, L AF Miele, L TI Points to consider in the manufacture and testing of monoclonal antibody products for human use (1997) SO JOURNAL OF IMMUNOTHERAPY LA English DT Article ID INFECTION; ANTIGEN; VIRUSES RP Miele, L (reprint author), NIH,DIV MONOCLONAL ANTIBODIES,CBER,US FDA,CAMPUS BLDG 29B,RM 3NN18,HFM-555,BETHESDA,MD 20892, USA. NR 28 TC 7 Z9 8 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAY PY 1997 VL 20 IS 3 BP 214 EP 243 PG 30 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA XA886 UT WOS:A1997XA88600007 ER PT J AU Mofenson, LM Korelitz, J Meyer, WA Bethel, J Rich, K Pahwa, S Moye, J Nugent, R Read, J AF Mofenson, LM Korelitz, J Meyer, WA Bethel, J Rich, K Pahwa, S Moye, J Nugent, R Read, J TI The relationship between serum human immunodeficiency virus type 1 (HIV-1) RNA level, CD4 lymphocyte percent, and long-term mortality risk in HIV-1-infected children SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT XIth International Conference on AIDS CY JUL 07-13, 1996 CL VANCOUVER, CANADA ID INTRAVENOUS IMMUNOGLOBULIN; INFECTED CHILDREN; BACTERIAL-INFECTIONS; NATURAL-HISTORY; PROPHYLAXIS AB Association of human immunodeficiency virus type 1 (HIV-1) RNA level, CD4 cell percent, and mortality was examined in stored sera from 254 infected children in an intravenous immunoglobulin infection prophylaxis trial, Ninety-two children (36.2%) died (41 during the study, 51 during longterm follow-up), The geometric mean baseline HIV-1 RNA level was 104,626 copies/mL, and the mean CD4 cell percent was 25%, Relative risk of death (RR) was 2.1 if the baseline RNA level was > 100,000 copies/mL (95% confidence interval [CI], 1.4-3.0) and was 3.0 if the baseline CD4 cell percent was < 15% (95% CI, 2.2-4.0), If RNA levels increased after baseline, the RR was 1.8 (95% CI, 1.3-2.6), and if the CD4 cell percent dropped to < 15%, the RR was 2.8 (95% CI, 1.6-4.9). In a multivariate model, both baseline RNA level and CD4 cell percent were independently associated with mortality risk. In a time-dependent model, the RR per log(10) increase in HIV-1 RNA copy numbers was 2.8 (95% CI, 2.1-3.6) and per 5 percentage point decrement in CD4 cell percent was 1.3 (95% CI, 1.2-1.5), Both variables should be considered for in decision-making regarding therapy and evaluation of antiretroviral response. C1 QUEST DIAGNOST INC,BALTIMORE,MD. UNIV ILLINOIS,SCH MED,CHICAGO,IL. WESTAT CORP,ROCKVILLE,MD. N SHORE UNIV HOSP,MANHASSET,NY. RP Mofenson, LM (reprint author), NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,CTR RES MOTHERS & CHILDREN,NIH,ROCKVILLE,MD 20852, USA. OI Mofenson, Lynne/0000-0002-2818-9808; moye, john/0000-0001-9976-8586 FU NICHD NIH HHS [HD-33162] NR 24 TC 178 Z9 183 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1997 VL 175 IS 5 BP 1029 EP 1038 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WW726 UT WOS:A1997WW72600001 PM 9129063 ER PT J AU Bakshi, SS Britto, P Capparelli, E Mofenson, L Fowler, MG Rasheed, S Schoenfeld, D Zimmer, B Frank, Y Yogev, R Jimenez, E Salgo, M Boone, G Pahwa, SG AF Bakshi, SS Britto, P Capparelli, E Mofenson, L Fowler, MG Rasheed, S Schoenfeld, D Zimmer, B Frank, Y Yogev, R Jimenez, E Salgo, M Boone, G Pahwa, SG TI Evaluation of pharmacokinetics, safety, tolerance, and activity of combination of zalcitabine and zidovudine in stable, zidovudine-treated pediatric patients with human immunodeficiency virus infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PHASE-I; EFFECTS MODELS; CHILDREN; 2',3'-DIDEOXYCYTIDINE; HIV; THERAPY; DIDEOXYCYTIDINE; SENSITIVITY; INHIBITION; DISEASE AB A double-blind phase II trial compared zalcitabine (0.03 mg/kg/day) in combination with zidovudine (720 mg/m(2)/day) and zidovudine monotherapy in 250 clinically stable, previously zidovudine-treated, human immunodeficiency virus-infected children, The combination was well-tolerated except for an increased incidence of neutropenia (14%) compared with that in children receiving monotherapy (5%), No differences were noted for time to first AIDS-defining illness or death, neuropsychologic status, or weight Z scores, In patients in the combination arm, the CD4 cell count decline was slower (13% per year) than in patients receiving monotherapy (25% per year) (P = .03), and quantitative peripheral blood mononuclear cell virus load remained lower at all time points (P = .08), Deaths were fewer in patients receiving combination therapy (4) compared with those in patients receiving monotherapy (10) (P = .083), Thus, administration of zidovudine with zalcitabine to children with prior zidovudine treatment did not result in a significant increase in toxicity compared with that resulting from zidovudine monotherapy and demonstrated improvement in immunologic and virologic surrogate markers. C1 CORNELL UNIV,N SHORE UNIV HOSP,COLL MED,MANHASSET,NY. FRONTIER SCI & TECHNOL RES FDN INC,AMHERST,NY. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. UNIV SO CALIF,LOS ANGELES,CA 90089. NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,CTR RES MOTHERS & CHILDREN,NIH,ROCKVILLE,MD. NIH,BETHESDA,MD 20892. NORTHWESTERN UNIV,SCH MED,CHICAGO CHILDRENS MEM HOSP,CHICAGO,IL. SAN JUAN CITY HOSP,PUERTO RICAN MED CTR,SAN JUAN,PR. HOFFMANN LA ROCHE INC,NUTLEY,NJ 07110. GLAXO WELLCOME INC,RES TRIANGLE PK,NC 27709. OI Mofenson, Lynne/0000-0002-2818-9808 NR 38 TC 21 Z9 22 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1997 VL 175 IS 5 BP 1039 EP 1050 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WW726 UT WOS:A1997WW72600002 PM 9129064 ER PT J AU DSouza, MP Livnat, D Bradac, JA Bridges, SH Bryson, Y Hanson, C Matthews, T Moore, J Trkola, A ZollaPazner, S Gorny, M Burton, D Merigan, T McNamara, J Norcross, M Posner, M Robinson, J ViraniKetter, N Barbas, CF Parren, P Katinger, H AF DSouza, MP Livnat, D Bradac, JA Bridges, SH Bryson, Y Hanson, C Matthews, T Moore, J Trkola, A ZollaPazner, S Gorny, M Burton, D Merigan, T McNamara, J Norcross, M Posner, M Robinson, J ViraniKetter, N Barbas, CF Parren, P Katinger, H TI Evaluation of monoclonal antibodies to human immunodeficiency virus type 1 primary isolates by neutralization assays: Performance criteria for selecting candidate antibodies for clinical trials SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID V3 LOOP; HIV-1; GP120; INFECTION; EPITOPE; BINDING; SITE AB A collaborative study was organized to identify monoclonal antibodies (MAbs) that may be broadly and potently neutralizing for a panel of human immunodeficiency virus type 1 (HIV-1) low-passaged adult and pediatric primary isolates in peripheral blood mononuclear cells, Five laboratories evaluated a coded panel of seven human MAbs to HIV-1 subtype B envelope V3, CD4 binding region, gp41, and other conformationally sensitive determinants. Each laboratory measured neutralizing activity of the MAbs against the laboratory isolate HIVMN and a panel of 9 subtype B primary isolates. Antibodies were classified as suitable candidates for future clinical studies if they could neutralize at least half of the 9 primary isolates at a concentration of less than or equal to 25 mu g/mL for 90% viral inhibition. The study identified three MAbs that met stated performance criteria: IgG1b12, 2G12, and 2F5. These results may provide a rationale for examining the clinical efficacy, either singly or in combination, of the three MAbs. RP DSouza, MP (reprint author), NIAID, DIV AIDS, NIH, 6003 EXECUT BLVD, ROOM 2C35, ROCKVILLE, MD 20892 USA. RI Trkola, Alexandra/K-2115-2012 OI Trkola, Alexandra/0000-0003-1013-876X FU NIAID NIH HHS [AI-27550, AI-35157, AI-35538] NR 24 TC 143 Z9 144 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1997 VL 175 IS 5 BP 1056 EP 1062 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WW726 UT WOS:A1997WW72600004 PM 9129066 ER PT J AU Davis, DA Humphrey, RW Newcomb, FM OBrien, TR Goedert, JJ Straus, SE Yarchoan, R AF Davis, DA Humphrey, RW Newcomb, FM OBrien, TR Goedert, JJ Straus, SE Yarchoan, R TI Detection of serum antibodies to a Kaposi's sarcoma-associated herpesvirus-specific peptide SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 4th Conference on Retroviruses and Opportunistic Infections CY JAN 22-27, 1997 CL WASHINGTON, DC ID EPSTEIN-BARR-VIRUS; DNA-SEQUENCES; SYNTHETIC PEPTIDES; AIDS; INFECTION; BLOOD AB Kaposi's sarcoma (KS)-associated herpesvirus/human herpesvirus type 8 (KSHV/HHV-8) may play an etiologic role in the pathogenesis of KS, In an attempt to assess KSHV/HHV-8 infection, an ELISA was developed using an 18-amino acid peptide from a putative minor capsid protein of KSHV/HHV-8 conjugated to bovine serum albumin, Overall, sera from human immunodeficiency virus type 1 (HIV-1)-positive patients with KS had a higher reactivity in the assay than did sera from HIV-1-positive patients without KS (P = .018). Of 35 HIV-1-positive patients with KS, 60% were antibody positive, compared with 27% of 33 HIV-1-positive patients without KS, Of 30 healthy blood donors, 20% were antibody positive, The ELISA responses did not correlate with antibody titers to Epstein-Barr virus, Given the homology and antigenic relatedness between KSHV/HHV-8 and Epstein-Barr virus, serologic assays involving unique KSHV/HHV-8 peptides may prove to be valuable in defining the epidemiology and clinical expression of this virus. C1 NCI,HIV & AIDS MALIGNANCY BRANCH,NIH,BETHESDA,MD 20892. NCI,VIRAL EPIDEMIOL BRANCH,NIH,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,NIH,BETHESDA,MD 20892. NR 42 TC 56 Z9 57 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1997 VL 175 IS 5 BP 1071 EP 1079 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WW726 UT WOS:A1997WW72600006 PM 9129068 ER PT J AU Burns, DN Landesman, S Wright, DJ Waters, D Mitchell, RM Rubinstein, A Willoughby, A Goedert, JJ AF Burns, DN Landesman, S Wright, DJ Waters, D Mitchell, RM Rubinstein, A Willoughby, A Goedert, JJ TI Influence of other maternal variables on the relationship between maternal virus load and mother-to-infant transmission of human immunodeficiency virus type 1 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT XIth International Conference on AIDS CY JUL 07-13, 1996 CL VANCOUVER, CANADA ID PLASMA; RNA; HIV-1; QUANTITATION AB To assess the relationship between maternal human immunodeficiency virus (HIV) type 1 RNA level, other important covariates, and mother-to-infant (vertical) transmission of HIV-1, third trimester repository specimens from 160 HIV-1-seropositive women enrolled in the Mothers and Infants Cohort Study between 1986 and 1991 were assayed in batch for HIV-1 RNA. A significant association between peripheral blood HIV-1 RNA level and vertical transmission remained after controlling far CD4 cell level, duration of ruptured membranes, ''hard'' drug (cocaine and heroin) use, and frequency of sexual activity during pregnancy, However, the association was attenuated among women with advanced HIV infection and those with a high frequency of sexual activity during pregnancy. In these settings, interventions that target risk factors other than virus load may be particularly important for preventing vertical transmission of HIV-1. C1 NCI,VIRAL EPIDEMIOL BRANCH,NIH,BETHESDA,MD. WESTAT CORP,ROCKVILLE,MD. SCI APPLICAT INT CORP,FREDERICK,MD. SUNNYBROOK HLTH SCI CTR,DEPT MED,BROOKLYN,NY. ALBERT EINSTEIN COLL MED,DEPT PEDIAT,BRONX,NY 10467. RP Burns, DN (reprint author), NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,NIH,6100 EXECUT BLVD,SUITE 4B11,ROCKVILLE,MD 20892, USA. FU NCI NIH HHS [CP-61013]; NICHD NIH HHS [HD-25714, HD-82913] NR 15 TC 52 Z9 55 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1997 VL 175 IS 5 BP 1206 EP 1210 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WW726 UT WOS:A1997WW72600025 PM 9129087 ER PT J AU Bouloc, A Katz, SI AF Bouloc, A Katz, SI TI Relative contributions of epidermal and dermal derived antigen presenting cells to the induction of contact hypersensitivity. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 1997 VL 108 IS 5 BP C4 EP C4 PG 1 WC Dermatology SC Dermatology GA WV133 UT WOS:A1997WV13300028 ER PT J AU Kassiou, M Ravert, HT Mathews, WB Musachio, JL London, ED Dannals, RF AF Kassiou, M Ravert, HT Mathews, WB Musachio, JL London, ED Dannals, RF TI Synthesis of 3-[(1-[C-11]methyl-2(S)-pyrrolidinyl)methoxy]pyridine and 3-[(1-[C-11]methyl-2(R)-pyrrolidinyl)methoxy]pyridine: Radioligands for in vivo studies of neuronal nicotinic acetylcholine receptors SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE nicotinic acetylcholine receptors; 3-pyridyl ethers; positron emission tomography; carbon-11 ID LIVING HUMAN-BRAIN; IN-VIVO; BINDING-SITES; DIVERSITY; EPIBATIDINE; TOMOGRAPHY; DEMENTIA; DOPAMINE; AGONIST; PET AB 3-[(1-[C-11]Methyl-2(S)-pyrrolidinyl)methoxy]pyridine, [C-11]A-84543, a selective radioligand for neuronal nicotinic acetylcholine receptors (nAChRs) was prepared by N-alkylation of N-desmethyl A-84543 with [C-11]methyl iodide in DMF. The radioligand was purified by semipreparative reverse-phase HPLC. The average specific radioactivity was 1755 mCi/mu mol calculated at end-of-synthesis (EOS). The average time of synthesis, including formulation, was 17 min. The pharmacologically less active (R) enantiomer, 3-[(1-[C-11]methyl-2(R)-pyrrolidinyl) methoxy]pyridine was synthesized in an analogous manner using the appropriate N-desmethyl precursor. The specific radioactivity wascalculated to be 2368 mCi/mu mol (EOS). C1 JOHNS HOPKINS MED INST,DEPT RADIOL,DIV NUCL MED,BALTIMORE,MD 21205. RP Kassiou, M (reprint author), NIDA,DIV INTERNAL RES,BRAIN IMAGING SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 27 TC 13 Z9 13 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD MAY PY 1997 VL 39 IS 5 BP 425 EP 431 PG 7 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA WY544 UT WOS:A1997WY54400009 ER PT J AU Sugg, DW Chesser, RK Long, JC AF Sugg, DW Chesser, RK Long, JC TI Assessment of genetic information in morphometric traits: Geographic patterns and evolutionary interpretation SO JOURNAL OF MAMMALOGY LA English DT Article DE Peromyscus; geographic patterns; heritability; morphometric traits; variance partitioning ID QUANTITATIVE CHARACTERS; MORPHOLOGICAL VARIATION; ENZYME HETEROZYGOSITY; PEROMYSCUS-ATTWATERI; TEXAS MOUSE; POPULATIONS; HERITABILITY; VARIANCE; DRIFT; SIZES AB Comparative studies often indicate a lack of concordant geographic patterns for morphometric and genic traits. Herein, it is shown that the genetic variance of morphometric traits can be partitioned into within- and among-group components as is traditionally done with genic data. Employing these methods demonstrates that there is considerable congruence for estimates of differentiation from genic and morphometric data for populations of the Texas mouse, Peromyscus attwateri. Within-group genetic variances of morphometric traits, relative to that of genic traits, also can be estimated. From these estimates, a pseudo-heritability can be obtained. Pseudo-heritabilities generally are low, indicating that evolutionary forces have removed much of the genetic variation within groups, or that environmental variation is considerable for morphometric traits. The combined use of genic and morphometric traits offer greater insight into past evolution that has lead to geographic patterns. C1 UNIV GEORGIA,SAVANNAH RIVER ECOL LAB,AIKEN,SC 29809. UNIV GEORGIA,DEPT GENET,ATHENS,GA 30602. NIH,NEUROGENET LAB,ROCKVILLE,MD 20852. NR 44 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC MAMMALOGISTS PI PROVO PA BRIGHAM YOUNG UNIV, DEPT OF ZOOLOGY, PROVO, UT 84602 SN 0022-2372 J9 J MAMMAL JI J. Mammal. PD MAY PY 1997 VL 78 IS 2 BP 405 EP 416 DI 10.2307/1382894 PG 12 WC Zoology SC Zoology GA XB316 UT WOS:A1997XB31600014 ER PT J AU Appelbaum, M Batten, DA Belsky, J Booth, C Bradley, R Brownell, C Caldwell, B Campbell, S ClarkeStewart, A Cohn, J Cox, M Fendt, K Friedman, S Goldberg, W Greenberger, E HirshPasek, K Huston, A Marshall, N McCartney, K OBrien, M Owen, MT Phillips, D Ricciuti, H Spieker, S Vandell, DL Weinraub, M AF Appelbaum, M Batten, DA Belsky, J Booth, C Bradley, R Brownell, C Caldwell, B Campbell, S ClarkeStewart, A Cohn, J Cox, M Fendt, K Friedman, S Goldberg, W Greenberger, E HirshPasek, K Huston, A Marshall, N McCartney, K OBrien, M Owen, MT Phillips, D Ricciuti, H Spieker, S Vandell, DL Weinraub, M TI Familial factors associated with the characteristics of nonmaternal care for infants SO JOURNAL OF MARRIAGE AND THE FAMILY LA English DT Article DE child care; coparental care; infant care; selection factors ID CHILD-CARE; MATERNAL EMPLOYMENT; 1ST YEAR; QUALITY; MOTHERS; CHOICE; PARTICIPATION; DETERMINANTS; PERSPECTIVES; OUTCOMES AB The extent to which family, economic, and psychosocial factors account-for age of initiation, amount, type, and quality of nonmaternal infant care was examined for 1,281 children in 10 locations around the U.S. Families were enrolled in the study when the infants were born, and information was collected about naturally occurring patterns of regular nonmaternal care over the first 15 months of the child's life. Economic factors were most consistently associated with the amount and the nature of the nonmaternal care that infants received; maternal personality and beliefs about maternal employment also were factors. Infants who began nonmaternal care between 3 and 5 months of age had mothers who scored highest on extraversion and agreeableness. Children who began nonmaternal care earlier had mothers who believed that maternal employment had greater benefits for children. More nonmaternal care was related to fewer children in the family, lower maternal education, higher maternal income, lower total family income, longer hours of maternal employment, and the mother's belief in the benefits of maternal employment. The type of care was related to the child's ethnicity, household composition, and the mother's concerns about the risks of maternal employment to children. Factors predicting the quality of care varied across different types of care. For care in the child's home or in a childcare home, family income was positively associated with quality. For care in child-care centers, children from both low- and high-income families received higher quality care than those from moderate-income families. These results define the potentially confounding factors to be considered when analyzing the effects of early experiences of nonmaternal care on child outcome. C1 PENN STATE UNIV,UNIVERSITY PK,PA 16802. UNIV WASHINGTON,SEATTLE,WA 98195. UNIV ARKANSAS,LITTLE ROCK,AR 72204. UNIV PITTSBURGH,PITTSBURGH,PA 15260. UNIV ARKANSAS MED SCI HOSP,LITTLE ROCK,AR 72205. UNIV CALIF IRVINE,IRVINE,CA 92717. UNIV N CAROLINA,CHAPEL HILL,NC. TEMPLE UNIV,PHILADELPHIA,PA 19122. UNIV KANSAS,LAWRENCE,KS 66045. WELLESLEY COLL,WELLESLEY,MA 02181. UNIV NEW HAMPSHIRE,DURHAM,NH 03824. UNIV TEXAS,DALLAS,TX 75230. NATL RES COUNCIL,OTTAWA,ON,CANADA. CORNELL UNIV,ITHACA,NY 14853. UNIV WISCONSIN,MADISON,WI. NICHHD,PUBL INFORMAT & COMMUN BRANCH,NIH,BETHESDA,MD 20892. RP Appelbaum, M (reprint author), VANDERBILT UNIV,NASHVILLE,TN, USA. RI Marshall, Nancy/C-3428-2012; OI Marshall, Nancy L/0000-0002-4799-2030; Belsky, Jay/0000-0003-2191-2503 NR 65 TC 109 Z9 109 U1 2 U2 8 PU NATL COUNCIL FAMILY RELATIONS PI MINNEAPOLIS PA 3989 CENTRAL AVE NE #550, MINNEAPOLIS, MN 55421 SN 0022-2445 J9 J MARRIAGE FAM JI J. Marriage Fam. PD MAY PY 1997 VL 59 IS 2 BP 389 EP 408 PG 20 WC Family Studies; Sociology SC Family Studies; Sociology GA XB094 UT WOS:A1997XB09400011 ER PT J AU McKee, TC Bokesch, HR McCormick, JL Rashid, MA Spielvogel, D Gustafson, KR Alavanja, MM Cardellina, JH Boyd, MR AF McKee, TC Bokesch, HR McCormick, JL Rashid, MA Spielvogel, D Gustafson, KR Alavanja, MM Cardellina, JH Boyd, MR TI Isolation and characterization of new anti-HIV and cytotoxic leads from plants, marine, and microbial organisms SO JOURNAL OF NATURAL PRODUCTS LA English DT Article; Proceedings Paper CT Young Investigators Symposium at the 37th Annual Meeting of the American-Society-of-Pharmacognosy CY 1996 CL SANTA CRUZ, CA SP Amer Soc Pharmocognosy ID SPONGE JASPIS-STELLIFERA; MALABARICANE TRITERPENES; ERYTHRINA-ERIOTRIOCHA; LICORICE ROOT; ISOFLAVONE; PHYTOALEXINS; PTEROCARPAN; COLLECTION; FLAVONOIDS; SIGMOIDEA AB New cytotoxic isomalabaricane triterpenes have been isolated from a sponge Stelletta sp. (1-7); anti-HIV pterocarpans (8 and 9) and isoflavanoids (12-16 and 18) were elucidated from two tropical plants in the genus Erythrina; and anti-HIV enniatins (20 and 22-23) were characterized from fungi in the genera Fusarium and Alternaria. The enniatins were evaluated for in vivo anti-HIV activity in the hollow fiber assay. RP McKee, TC (reprint author), NCI,LAB DRUG DISCOVERY RES & DEV,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT DIAG & CTR,FREDERICK,MD 21702, USA. NR 39 TC 97 Z9 106 U1 0 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD MAY PY 1997 VL 60 IS 5 BP 431 EP 438 DI 10.1021/np970031g PG 8 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA XA685 UT WOS:A1997XA68500001 PM 9170286 ER PT J AU Grant, BF Pickering, RP AF Grant, BF Pickering, RP TI Familial aggregation of DSM-IV alcohol use disorders: Examination of the primary-secondary distinction in a general population sample SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID MAJOR DEPRESSIVE DISORDER; PSYCHIATRIC-DISORDERS; HISTORY METHOD; RELIABILITY; UNIPOLAR AB This study examined the familial aggregation of alcoholism in subgroups of respondents classified with respect to the primary-secondary distinction as it is related to DSM-IV major depression and alcohol use disorders. Rates of alcoholism among specific first- and second-degree relatives of male and female probands with primary, secondary, and concurrent depression (i.e., the comorbid groups) and with major depression only were compared with one another and with a normal control group. The results of this general population survey that uses a large representative sample of the U.S. were at variance with some findings from the clinical literature with regard to familial aggregation. Greater rates of alcoholism were found among first- and second-degree relatives of the major depression only group compared with normal controls. Male and female probands of all three comorbid groups were not shown to convey a greater risk of alcoholism to their offspring compared with the normal control group or the major depression only group. The discrepancy between clinical research findings and those of this general population study were discussed in terms of methodological considerations. RP Grant, BF (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,SUITE 514,6000 EXECUT BLVD,MSC 7003,BETHESDA,MD 20892, USA. NR 25 TC 7 Z9 7 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD MAY PY 1997 VL 185 IS 5 BP 335 EP 343 DI 10.1097/00005053-199705000-00008 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WZ822 UT WOS:A1997WZ82200008 PM 9171811 ER PT J AU DePetrillo, PB AF DePetrillo, PB TI Calcium-activated neutral protease activity is decreased in PC12 cells after ethanol exposure SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE calpain; ethanol; PC12 cells ID NERVE GROWTH-FACTOR; KINASE-C; CALPAIN; PROTEOLYSIS; CHANNELS; SUBUNIT; BINDING; SITES AB Calcium-activated neutral protease activity was determined in PC12 cells exposed to ethanol for 96 h using a fluorescence-based assay with N-succinyl-Leu-Tyr 7-amido-4-methylcoumarin as the substrate, Stimulated activity was measured at high (1,400 mu M) or low (140 mu M) Ca2+ concentrations in the presence of 20 mu M ionomycin. Kinetic parameters were derived by fitting a model relating fluorescence intensity to time: F-t = F-final* (1 - e(-kobst)). Cell extracts were subjected to nondenaturing gel electrophoresis and casein zymography with quantification of the activity of the two calpain isoforms. Exposure to ethanol significantly decreased whole cell calpain activity measured by k(obs) beginning at 20 mM, to 27.8% of control at 1,400 mu M Ca2+ and 29.2% of control at 140 mu M Ca2+ in the presence of 20 mu M ionomycin. No changes in mu-calpain or m-calpain activities were found in cell extracts from cells exposed to 20 mM ethanol, whereas at 40 and 80 mM ethanol, significant decreases in both mu-calpain and m-calpain activities were discovered. RP DePetrillo, PB (reprint author), NIAAA,INTRAMURAL RES PROGRAM,CLIN STUDIES LAB,NIH,10-3C103,10 CTR DR,MSC 1256,BETHESDA,MD 20892, USA. NR 22 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 1997 VL 68 IS 5 BP 1863 EP 1869 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA WU248 UT WOS:A1997WU24800010 PM 9109511 ER PT J AU Schetz, JA Sibley, DR AF Schetz, JA Sibley, DR TI Zinc allosterically modulates antagonist binding to cloned D-1 and D-2 dopamine receptors SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE d-transition metals; cations; spiperone; SCH-23390; G protein-coupled receptor ID MUSCARINIC RECEPTORS; EXPRESSION; RELEASE; LIGANDS; CYCLASE; CLONING; BRAIN AB Cations of various size and charge were used as atomic scale probes of D-1 and D-2 dopamine receptors, Those cations that perturbed the binding of D-1- and D-2-selective dopamine receptor antagonists were identified by screening at 5 mM cation. Pseudo-noble-gas-configuration d-transition metals, such as zinc, exerted a complete inhibition of specific binding, whereas most other cations had little or no effect. The nature of zinc's actions was characterized by measuring the radioligand binding properties of [H-3]SCH-23390 and [H-3]methylspiperone to cloned D-1A and D-2L dopamine receptors in either the presence or absence of Zn2+. Zinc exerts a low-affinity, dose-dependent, EDTA-reversible inhibition of the binding of subtype-specific antagonists primarily by decreasing the ligands' affinity for their receptors. The mechanism of zinc inhibition appears to be allosteric modulation of the dopamine receptor proteins because zinc increases the dissociation constant (K-D) of ligand binding, Schild-type plots of zinc inhibition reach a plateau, and zinc accelerates antagonist dissociation rates. Here we demonstrate the effect of zinc on the binding of D-1- and D-2-selective antagonists to cloned dopamine receptors and show that the inhibition by zinc is through a dose-dependent, reversible, allosteric, two-state modulation of dopamine receptors. RP Schetz, JA (reprint author), NINCDS,EXPT THERAPEUT BRANCH,NIH,MOL NEUROPHARMACOL SECT,BLDG 10,ROOM 5C-108,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 20 TC 48 Z9 49 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 1997 VL 68 IS 5 BP 1990 EP 1997 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA WU248 UT WOS:A1997WU24800024 PM 9109525 ER PT J AU Chrapusta, SJ Wyatt, RJ Masserano, JM AF Chrapusta, SJ Wyatt, RJ Masserano, JM TI Effects of single and repeated footshock on dopamine release and metabolism in the brains of Fischer rats SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE frontal cortex; nucleus accumbens; 3-methoxytyramine; 3,4-dihydroxyphenylacetic acid; homovanillic acid; stress ID MEDIAL PREFRONTAL CORTEX; EXPERIENCES DIFFERENTLY AFFECT; CATECHOL-O-METHYLTRANSFERASE; TIME-DEPENDENT RESPONSES; NUCLEUS-ACCUMBENS; MESOLIMBIC DOPAMINE; EXTRACELLULAR DOPAMINE; FRONTAL-CORTEX; STRESS; STRIATUM AB Changes in the tissue levels of 3-methoxytyramine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and dopamine in the frontal cortex, hypothalamus, nucleus accumbens, and striatum were evaluated after 0.5-4 h of footshock (2 mA, for 3 s every 30 +/- 5 s) in Fischer rats. 3-MT, DOPAC, and HVA levels in the four brain areas peaked at 0.5 h and in most cases returned to baseline values within 4 h. No changes were found in dopamine levels. Repeated footshock stress was evaluated by administering 10 footshock sessions (0.5 h, two per day for 5 days). At the end of the 10th footshock session, 3-MT levels were higher than at the end of the first footshock session in three of the four brain regions, indicating sensitization of dopamine release. No differences were found between the first and 10th footshock sessions in DOPAC and HVA levels. Fourteen days after the 10th footshock session, the levels of 3-MT, DOPAC, and HVA were the same as in control rats in all four brain regions, A 0.5-h footshock challenge presented 14 days after the 10th footshock session attenuated DOPAC levels in the hypothalamus and nucleus accumbens, In contrast, DOPAC and HVA levels in the frontal cortex showed sensitization after footshock challenge, and a similar trend was apparent for 3-MT levels, These results indicate that repeated footshock stress induces generalized sensitization of dopamine release and turnover in some areas of the brain of Fischer rats. This sensitization may persist in the cortical but not subcortical dopamine neurons after discontinuation of the treatment. C1 NIMH,NEUROSCI CTR ST ELIZABETHS,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. NR 52 TC 37 Z9 37 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 1997 VL 68 IS 5 BP 2024 EP 2031 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA WU248 UT WOS:A1997WU24800027 PM 9109528 ER PT J AU Rabin, O Deutsch, J Grange, E Pettigrew, KD Chang, MCJ Rapoport, SI Purdon, AD AF Rabin, O Deutsch, J Grange, E Pettigrew, KD Chang, MCJ Rapoport, SI Purdon, AD TI Changes in cerebral acyl-CoA concentrations following ischemia-reperfusion in awake gerbils SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE ischemia; fatty acid metabolism; phospholipid metabolism; acyl-CoA; brain; gerbil ID FREE FATTY-ACIDS; PLATELET-ACTIVATING FACTOR; DELAYED NEURONAL DEATH; COENZYME-A SYNTHETASE; RAT-BRAIN MICROSOMES; TRANSIENT ISCHEMIA; ENERGY METABOLITES; BILATERAL ISCHEMIA; LIPID-METABOLISM; MAMMALIAN-CELLS AB Transient global cerebral ischemia affects phospholipid metabolism and features a considerable increase in unesterified fatty acids. Reincorporation of free fatty acids into membrane phospholipids during reperfusion following transient ischemia depends on conversion of fatty acids to acyl-CoAs via acyl-CoA synthetases and incorporation of the acyl group into lysophospholipids. To study the effect of ischemia-reperfusion on brain fatty acid and acyl-CoA pools, the common carotid arteries were tied for 5 min in awake gerbils, after which the ligatures were released for 5 min and the animals were killed by microwave irradiation. Twenty percent of these animals (two of 10) were excluded from the ischemia-reperfusion group when it was demonstrated statistically that brain unesterified arachidonic acid concentration was not elevated beyond the range of the control group, Brain unesterified fatty acid concentration was increased 4.4-fold in the ischemic-reperfused animals, with stearic acid and arachidonic acid increasing the most among the saturated and polyunsaturated fatty acids, respectively, The total acyl-CoA concentration remained unaffected, indicating that reacylation of membrane lysophospholipids is maintained during recovery. However, there was a substantial increase in the stearoyl- and arachidonoyl-CoA and a marked decrease in palmitoyl- and docosahexaenoyl-CoA. These results suggest that unesterified fatty acid reacylation into phospholipids is reprioritized according to the redistribution in concentration of acyl-CoA molecular species, with incorporation of stearic acid and especially arachidonic acid being favored. C1 NIA,NEUROSCI LAB,NIH,BETHESDA,MD 20892. NIMH,DIV EPIDEMIOL & SERV RES,NIH,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,SCH PHARM,DEPT PHARMACEUT CHEM,IL-91120 JERUSALEM,ISRAEL. NR 58 TC 29 Z9 30 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 1997 VL 68 IS 5 BP 2111 EP 2118 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA WU248 UT WOS:A1997WU24800038 PM 9109539 ER PT J AU Ozaki, N Manji, H Lubierman, V Lu, SJ Lappalainen, J Rosenthal, NE Goldman, D AF Ozaki, N Manji, H Lubierman, V Lu, SJ Lappalainen, J Rosenthal, NE Goldman, D TI A naturally occurring amino acid substitution of the human serotonin 5-HT2A receptor influences amplitude and timing of intracellular calcium mobilization SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE serotonin 5-HT2A receptor; polymorphism; calcium; platelet ID SEASONAL AFFECTIVE-DISORDER; HUMAN-BLOOD PLATELETS; PROTEIN-KINASE-C; LITHIUM TREATMENT; FRONTAL-CORTEX; BINDING; DESENSITIZATION; GENE; CA-2+; INDEXES AB Recently, two naturally occurring amino acid substitutions were identified in the C-terminal region of the serotonin 5-HT2A receptor. One of these, His(452)Tyr, has a rarer allele Tyr frequency of 9%. If (452)Tyr alters 5-HT2A function, it would thus be a candidate allele for human neurobehavioral variation. The present study was designed to evaluate the potential influence of the (452)His and (452)Tyr alleles on cellular 5-HT2A functions. Platelet 5-HT2A binding and 5-HT-induced Ca2+ response were compared in eight (452)His/(452)His homozygous and eight (452)His/(452)Tyr heterotygous individuals matched for sex, age, and diagnosis (all were patients with seasonal affective disorder). There was no difference in 5-HT2A binding measured using I-125-lysergic acid diethylamide, Nor were levels of G-protein subunits or PKC alpha, delta, epsilon, or zeta significantly altered. However, when Ca2+ response was stimulated by 2, 5, 10, or 25 mu M 5-HT, significant differences were found. In (452)His/(452)Tyr heterozygotes, (452)Tyr was associated with both smaller peak amplitude in Ca2+ mobilization and a different time course of response, with slower peak latency and longer half-time in (452)His/(452)Tyr heterozygotes compared with (452)His/(452)His homozygotes. The overall difference in the response of the 5-HT2A receptor in individuals with (452)Tyr was a blunting of the shape of the Ca2+ mobilization peak. The data reported here suggest that the primary sequence of this intracellular domain is important in function of the receptor and that the (452)His and (452)Tyr 5-HT2A alleles should be carefully evaluated for effects on human neurobehavioral variation. C1 NIMH,CLIN PSYCHOBIOL BRANCH,NIH,BETHESDA,MD 20892. NIMH,CLIN PHARMACOL SECT,EXPT THERAPEUT BRANCH,NIH,BETHESDA,MD 20892. NIAAA,NEUROGENET LAB,NIH,BETHESDA,MD 20892. RP Ozaki, N (reprint author), FUJITA HLTH UNIV,SCH MED,DEPT PSYCHIAT,TOYOAKE,AICHI 47011,JAPAN. RI Ozaki, Norio/M-8908-2014; Goldman, David/F-9772-2010 OI Ozaki, Norio/0000-0002-7360-4898; Goldman, David/0000-0002-1724-5405 NR 47 TC 88 Z9 90 U1 0 U2 5 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 1997 VL 68 IS 5 BP 2186 EP 2193 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA WU248 UT WOS:A1997WU24800046 PM 9109547 ER PT J AU DeVries, AC Young, WS Nelson, RJ AF DeVries, AC Young, WS Nelson, RJ TI Reduced aggressive behaviour in mice with targeted disruption of the oxytocin gene SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE agonistic behaviour; social behaviour; pituitary; sensorimotor; octapeptide; genetic knock-out ID MATERNAL-BEHAVIOR; RECEPTOR; RATS AB Oxytocin (OT) has been reported to mediate aggressive and affiliative behaviours in several species. The behavioural role of OT has been established with physiological manipulations that potentially affected blood pressure, which may have indirectly affected the behaviours under study. To provide converging evidence of the physiological role of OT in aggressive behavior, wild type (WT), heterozygous (OT-/+), and homozygous (OT-/-) mutant mice were tested in two aggression paradigms. In general, there was no significant difference in aggressiveness between WT and OT-/+ mice. However, there were significant reductions in the duration of aggressive behaviors among OT-/- animals, especially in agonistic encounters within neutral arenas. The OT-/- mice did not exhibit any sensorimotor deficits or display any altered general anxiety levels that may have accounted for the observed reduction in aggressive behavior, These data indicate that aggression is mediated in part by OT in mice and that increased aggressiveness is not an obligatory phenotypic result of targeted genetic disruption of any gene. C1 NIMH,LABS BEHAV PHARMACOL,NIH,BETHESDA,MD 20892. NIMH,LAB CELLULAR & MOL REGULAT,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,DEPT PSYCHOL,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,DEPT NEUROSCI,BEHAV NEUROENDOCRINOL GRP,BALTIMORE,MD 21218. RI Young, W Scott/A-9333-2009; OI Young, W Scott/0000-0001-6614-5112; Nelson, Randy/0000-0002-8194-4016 FU NICHD NIH HHS [HD 22201]; NIMH NIH HHS [MH 57535] NR 24 TC 75 Z9 76 U1 3 U2 8 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD MAY PY 1997 VL 9 IS 5 BP 363 EP 368 DI 10.1046/j.1365-2826.1997.t01-1-00589.x PG 6 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA XA611 UT WOS:A1997XA61100005 PM 9181490 ER PT J AU Rosener, M Muraro, PA Riethmuller, A Kalbus, M Sappler, G Thompson, RJ Lichtenfels, R Sommer, N McFarland, HF Martin, R AF Rosener, M Muraro, PA Riethmuller, A Kalbus, M Sappler, G Thompson, RJ Lichtenfels, R Sommer, N McFarland, HF Martin, R TI 2',3'-cyclic nucleotide 3'-phosphodiesterase: A novel candidate autoantigen in demyelinating diseases SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE 2',3'-cyclic nucleotide 3'-phosphodiesterase; multiple sclerosis; T-cell-response ID MULTIPLE-SCLEROSIS; BRAIN; LOCALIZATION; SPECIFICITY AB Autoaggressive T-cells specific for myelin proteins like proteolipid protein (PLP) and myelin basic protein (MBP) are thought to play a major role in the pathogenesis of demyelinating diseases of the central nervous system (CNS), 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) is the third most abundant myelin protein in the CNS. Due to lack of supply with enough CNPase of sufficient purity its immunologic properties have not been studied yet. We subcloned a human CNPase cDNA and expressed human recombinant CNPase (rh-CNPase) in E. coli. Purification of the protein was achieved by Ni2+-chelating chromatography. Furthermore we describe for the first time several rh-CNPase specific-T-cell lines from a multiple sclerosis patient and a healthy control. C1 NINCDS,NEUROIMMUNOL BRANCH,NIH,BETHESDA,MD 20892. UNIV SOUTHAMPTON,SOUTHAMPTON GEN HOSP,FAC MED,SOUTHAMPTON SO9 4XY,HANTS,ENGLAND. RP Rosener, M (reprint author), UNIV TUBINGEN,DEPT NEUROL,HOPPE SEYLER STR 3,D-72076 TUBINGEN,GERMANY. NR 16 TC 21 Z9 21 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD MAY PY 1997 VL 75 IS 1-2 BP 28 EP 34 DI 10.1016/S0165-5728(96)00230-5 PG 7 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA WV728 UT WOS:A1997WV72800004 PM 9143234 ER PT J AU Davis, DG Ross, GW Petrovitch, H White, LR Hardman, JM Nelson, JS Thiessen, P Wang, HZ Patel, E Markesbery, WR AF Davis, DG Ross, GW Petrovitch, H White, LR Hardman, JM Nelson, JS Thiessen, P Wang, HZ Patel, E Markesbery, WR TI Quantitation of argyrophilic grains in hippocampal CA-1 of aged Japanese-American men SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 UNIV KENTUCKY,SANDERS BROWN CTR AGING,LEXINGTON,KY 40536. UNIV HAWAII,HONOLULU,HI 96822. DEPT VET AFFAIRS,KUAKINI MED CTR,HONOLULU,HI. LOUISIANA STATE UNIV,NEW ORLEANS,LA. NIA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1997 VL 56 IS 5 BP 66 EP 66 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA WY073 UT WOS:A1997WY07300078 ER PT J AU Manor, Y Rinzel, J Segev, I Yarom, Y AF Manor, Y Rinzel, J Segev, I Yarom, Y TI Low-amplitude oscillations in the inferior olive: A model based on electrical coupling of neurons with heterogeneous channel densities SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID BETA-CELLS; RAT; CAT; MODULATION; INVITRO; SYSTEM; ORGANIZATION; CEREBELLUM; DISCHARGE; FREQUENCY AB The mechanism underlying subthreshold oscillations in inferior olivary cells is not known. To study this question, we developed a single-compartment, two-variable, Hodgkin-Huxley-like model for inferior olive neurons. The model consists of a leakage current and a low-threshold calcium current, whose kinetics were experimentally measured in slices. Depending on the maximal calcium and leak conductances, we found that a neuron model's response to current injection could be of four qualitatively different types: always stable, spontaneously oscillating, oscillating with injection of current, and bistable with injection of current. By the use of phase plane techniques, numerical integration, and bifurcation analysis, we subdivided the two-parameter space of channel densities into four regions corresponding to these behavioral types. We further developed, with the use of such techniques, an empirical rule of thumb that characterizes whether two cells when coupled electrically can generate sustained, synchronized oscillations like those observed in inferior olivary cells in slices. of low amplitude (0.1-10 mV) in the frequency range 4-10 Hz. We found that it is not necessary for either cell to be a spontaneous oscillator to obtain a sustained oscillation. On the Ether hand, two spontaneous oscillators always form an oscillating network when electrically coupled with any arbitrary coupling conductance. In the case of an oscillating pair of electrically coupled nonidentical cells, the coupling current varies periodically and is nonzero even for very large coupling values. The coupling current acts as an equalizing current to reconcile the differences between the two cells' ionic currents. It transiently depolarizes one cell and/or hyperpolarizes the other cell to obtain the regenerative response(s) required For the synchronized oscillation. We suggest that the subthreshold oscillations observed in the inferior olive can emerge from the electrical coupling between neurons with different channel densities, even if the inferior alive nucleus contains no or just a small proportion of spontaneously oscillating neurons. C1 HEBREW UNIV JERUSALEM,DEPT NEUROBIOL,IL-91904 JERUSALEM,ISRAEL. HEBREW UNIV JERUSALEM,INTERDISCIPLINARY CTR NEURAL COMPUTAT,IL-91904 JERUSALEM,ISRAEL. NIDDKD,BETHESDA,MD 20814. NR 52 TC 126 Z9 126 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 1997 VL 77 IS 5 BP 2736 EP 2752 PG 17 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA WZ563 UT WOS:A1997WZ56300036 PM 9163389 ER PT J AU Xie, KW Wang, T Olafsson, P Mizuno, K Lu, B AF Xie, KW Wang, T Olafsson, P Mizuno, K Lu, B TI Activity-dependent expression of NT-3 in muscle cells in culture: Implications in the development of neuromuscular junctions SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neurotrophins; RT-PCR; activity-dependent; membrane depolarization; neuromuscular synapse; nerve muscle co-culture ID NERVE GROWTH-FACTOR; MESSENGER-RNA EXPRESSION; NEUROTROPHIC FACTOR; ACETYLCHOLINE-RECEPTOR; SYNAPTIC TRANSMISSION; HIPPOCAMPAL-NEURONS; XENOPUS NERVE; MOTOR-NEURONS; FACTOR FAMILY; IDENTIFIED MOTONEURONS AB Although activity-dependent expression of neurotrophins has been studied extensively in the CNS, its physiological role during synapse development is not well established. At the developing neuromuscular junction in culture, exogenous application of the neurotrophin BDNF or NT-3 has been shown to acutely potentiate synaptic transmission and chronically promote synapse maturation. Using the same cell culture model, we have investigated activity-dependent neurotrophin expression in muscle cells and its role in developing neuromuscular synapses. Membrane depolarization, elicited by either depolarizing agents or repetitive electric stimulation, rapidly and specifically increased the levels of NT-3 mRNA in developing Xenopus laevis muscle cells in culture. NT-3 gene expression also was enhanced by acetylcholine (ACh), the neurotransmitter that causes muscle membrane depolarization. The effects of depolarization were mediated by increasing intracellular calcium concentration. Moreover, factor(s) induced by membrane depolarization appeared to enhance synaptic transmission at the developing neuromuscular junction. The frequency of spontaneous synaptic currents (SSCs) recorded from neuromuscular synapses was increased significantly after treatment with conditioned medium from depolarized muscle cultures. The amplitude, rise time, and decay time of SSCs were not affected, indicating a presynaptic action of the conditioned medium. The effects of the conditioned medium were blocked, partially, by the NT-3 scavenger TrkC-lgG, suggesting that the potentiation of synaptic efficacy was attributable, at least in part, to elevated NT-3 as a consequence of muscle depolarization. Thus, activity-dependent expression of muscle NT-3 may contribute to the development of the neuromuscular synapse. C1 NICHHD,UNIT SYNAPSE DEV & PLAST,NIH,DEV NEUROBIOL LAB,BETHESDA,MD 20892. RI Lu, Bai/A-4018-2012 NR 90 TC 71 Z9 74 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 1 PY 1997 VL 17 IS 9 BP 2947 EP 2958 PG 12 WC Neurosciences SC Neurosciences & Neurology GA WU675 UT WOS:A1997WU67500004 PM 9096131 ER PT J AU Kubota, R Jacobson, S AF Kubota, R Jacobson, S TI Immunopathogenesis of HAM/TSP: Involvement of HTLV-I specific CD8+ lymphocytes SO JOURNAL OF NEUROVIROLOGY LA English DT Article; Proceedings Paper CT 1st International Symposium of Neurovirology CY MAY 05-07, 1997 CL PHILADELPHIA, PA SP Allegheny Univ Hlth Sci, Ctr Neurovirol & Neurooncol DE human T lymphotropic virus type I (HTLV-I); HTLV-I-associated myelopathy tropical spastic paraparesis (HAM/TSP); CD8 lymphocytes ID TROPICAL SPASTIC PARAPARESIS; SPINAL-CORD LESIONS; VIRUS TYPE-I; NEUROLOGICAL DISEASE; CEREBROSPINAL-FLUID; PROVIRAL DNA; MYELOPATHY; ANTIBODIES; CELLS C1 NINDS,NEUROIMMUNOL BRANCH,VIRAL IMMUNOL SECT,BETHESDA,MD 20892. NR 23 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD MAY PY 1997 VL 3 SU 1 BP S6 EP S8 PG 3 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA XD312 UT WOS:A1997XD31200004 ER PT J AU Buvat, I Carson, JM Bartlett, ML Kitsiou, AN Srinivasan, G Nour, KA Dilsizian, V Chen, CC Bacharach, SL AF Buvat, I Carson, JM Bartlett, ML Kitsiou, AN Srinivasan, G Nour, KA Dilsizian, V Chen, CC Bacharach, SL TI ''Nuclear M-Mode'': A new method for evaluating gated myocardial perfusion/metabolism studies. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 U66 INSERM,PARIS,FRANCE. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 4 EP 4 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000004 ER PT J AU Carrasquillo, JA Lang, L Whatley, M Herscovitch, P Wang, QC Pastan, I Eckelman, WC AF Carrasquillo, JA Lang, L Whatley, M Herscovitch, P Wang, QC Pastan, I Eckelman, WC TI Use of a commercially available amino acid solution to block renal uptake of F-18 fluoromethylbenzoyl (FMB)-dsFv SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 28 EP 28 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000028 ER PT J AU Endres, CJ Carson, RE AF Endres, CJ Carson, RE TI Measurement of neurotransmitter release with bolus or infusion delivery of receptor-binding tracers. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,CTR CLIN,PET DEPT,BETHESDA,MD 20892. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 31 EP 31 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000031 ER PT J AU Bencherif, B Gorelick, D Nelson, R Stauffer, R Ravert, HT Mathews, WB Musachio, JL Dannals, RF Frost, JJ AF Bencherif, B Gorelick, D Nelson, R Stauffer, R Ravert, HT Mathews, WB Musachio, JL Dannals, RF Frost, JJ TI Measurement of brain Mu opioid receptor binding by PET in chronic cocaine users during early and prolonged monitored abstinence. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NIDA,DIR,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 122 EP 122 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000122 ER PT J AU Villemagne, VL Rothman, RB Yokoi, F Finley, P Rice, KC Chen, A Matecka, D Ravert, HT Mathews, WB Musachio, JL Dannals, RF Wong, DF AF Villemagne, VL Rothman, RB Yokoi, F Finley, P Rice, KC Chen, A Matecka, D Ravert, HT Mathews, WB Musachio, JL Dannals, RF Wong, DF TI Substantial occupancy of dopamine transporters by GBR12909, a potential treatment agent for cocaine addiction, as measured by PET. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 JOHNS HOPKINS MED INST,NIDA,ARC,BALTIMORE,MD 21205. NIDDK,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 123 EP 123 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000123 ER PT J AU Seidel, J Johnson, C Jagoda, E Sha, L Eckelman, WC Green, MV AF Seidel, J Johnson, C Jagoda, E Sha, L Eckelman, WC Green, MV TI A high resolution scanner for investigating technical requirements and selected biological applications of continuous 3D detectors in small animal PET. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 157 EP 157 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000157 ER PT J AU Heinz, A Ragan, P Jones, DW Hommer, D Williams, W Knable, MV Gorey, JG Lee, KS Weinberger, DR Linnoila, M AF Heinz, A Ragan, P Jones, DW Hommer, D Williams, W Knable, MV Gorey, JG Lee, KS Weinberger, DR Linnoila, M TI Reduced binding potential of serotonin transporters in the raphe of alcohol-dependent patients: An [I-123]beta-CIT SPECT study. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIMH,NEUROSCI CTR ST ELIZABETHS,WASHINGTON,DC 20032. NIAAA,WASHINGTON,DC. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 174 EP 174 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000174 ER PT J AU Kim, MK Sidel, J Le, N Kim, LS Yoo, TM Barker, C Kobayashi, H Green, MV Carrasquillo, JA Paik, CH AF Kim, MK Sidel, J Le, N Kim, LS Yoo, TM Barker, C Kobayashi, H Green, MV Carrasquillo, JA Paik, CH TI Evaluation of Tc-99m-mercaptoacetyltriglycine (MAG3)-biocytin as a new hepatobiliary agent in bilirubin-coinjected mice. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 181 EP 181 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000181 ER PT J AU Barendswaard, EC ODonoghue, JA Larson, SM Tschmelitsch, J Welt, S Schlom, J Scott, A Humm, JL AF Barendswaard, EC ODonoghue, JA Larson, SM Tschmelitsch, J Welt, S Schlom, J Scott, A Humm, JL TI Comparison of the effectiveness of radioimmunotherapy and fractionated radiotherapy. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MSKCC,LUDWIG INST CANC RES,NEW YORK,NY. MSKCC,NUCL MED SERV,DEPT RADIOL,NEW YORK,NY. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 212 EP 212 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000212 ER PT J AU Musachio, JL Scheffel, U Villemagne, V Horti, A Finley, P Xiao, Y DavilaGarcia, M Kellar, KJ Ravert, HT Mathews, WB London, ED Dannals, RF AF Musachio, JL Scheffel, U Villemagne, V Horti, A Finley, P Xiao, Y DavilaGarcia, M Kellar, KJ Ravert, HT Mathews, WB London, ED Dannals, RF TI [C-11] and [I-123/125] (+)- and (-)-MeIPH: Analogs of epibatidine for in vivo studies of nicotinic acetylcholine receptors. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NIDA,DIV INTRAMURAL RES,BALTIMORE,MD. GEORGETOWN UNIV,DEPT PHARMACOL,WASHINGTON,DC. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 235 EP 235 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000235 ER PT J AU Kassiou, M Scheffel, UA Ravert, HT Mathews, WB Musachio, JL London, ED Dannals, RF AF Kassiou, M Scheffel, UA Ravert, HT Mathews, WB Musachio, JL London, ED Dannals, RF TI C-11 A-84543: An enantioselective ligand for in vivo studies of neuronal nicotinic acetylcholine receptors. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIDA,BRAIN IMAGING SECT,BALTIMORE,MD. JOHNS HOPKINS MED INST,DIV NUCL MED,BALTIMORE,MD 21205. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 236 EP 236 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000236 ER PT J AU Carson, RE Schmall, B Endres, CJ Lang, L Der, MG Adams, HR Jagoda, E Herscovitch, P Eckelman, WC AF Carson, RE Schmall, B Endres, CJ Lang, L Der, MG Adams, HR Jagoda, E Herscovitch, P Eckelman, WC TI Kinetic analysis of the 5-HT1A antagonist [carbonyl-C-11]WAY-100635. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,PET DEPT,BETHESDA,MD 20892. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 296 EP 296 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000296 ER PT J AU Riddell, C Barker, WC Bacharach, SL AF Riddell, C Barker, WC Bacharach, SL TI Effects of scatter contamination in Tc-99m/Gd-153 simultaneous emission transmission cardiac studies. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 329 EP 329 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000329 ER PT J AU Morris, ED Chefer, SI London, ED AF Morris, ED Chefer, SI London, ED TI A two-scan graphical method to correct estimates of binding potential for the effects of mass of injected ligand. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIDA,BRAIN IMAGING CTR,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 345 EP 345 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000345 ER PT J AU Bae, SK Chen, CC Barker, WC Jensen, RT Gibril, F Doppman, JL Reynolds, JC AF Bae, SK Chen, CC Barker, WC Jensen, RT Gibril, F Doppman, JL Reynolds, JC TI In-111 pentetreotide scanning: ROC curve analysis of imaging methods. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 380 EP 380 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000380 ER PT J AU Buvat, I Bartlett, ML Carson, JM Kitsiou, AN Srinivasan, G Nour, KA Dilsizian, V Chen, CC Bacharach, SL AF Buvat, I Bartlett, ML Carson, JM Kitsiou, AN Srinivasan, G Nour, KA Dilsizian, V Chen, CC Bacharach, SL TI Quantitative analysis of Nuclear M-Mode images in cardiac gated perfusion/metabolic studies. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 INSERM,U66,PARIS,FRANCE. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 473 EP 473 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000473 ER PT J AU Mansour, P Bartlett, ML Bacharach, SL AF Mansour, P Bartlett, ML Bacharach, SL TI Multiple time-point fitting: Improving absolute measurements of myocardial wall thickening from gated perfusion/metabolism studies. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 474 EP 474 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000474 ER PT J AU Channing, MA Lang, LX Jagoda, E Vera, D Eckelman, WC AF Channing, MA Lang, LX Jagoda, E Vera, D Eckelman, WC TI Fluroine-18 labeled biotin analogs: Potential ligands for antibody-streptavidin conjugates SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,PET DEPT,WARREN GRANT MAGNUSON CLIN CTR,BETHESDA,MD 20892. UNIV CALIF DAVIS,MED CTR,SACRAMENTO,CA 95817. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 533 EP 533 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000533 ER PT J AU Kim, IS Yoo, TM Kobayashi, H Kim, MK Wang, QC Pastan, I Carrasquillo, JA Paik, CH AF Kim, IS Yoo, TM Kobayashi, H Kim, MK Wang, QC Pastan, I Carrasquillo, JA Paik, CH TI Lowering pI of anti-Tac dsFv reduces renal uptake of its Tc-99m label. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 792 EP 792 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000698 ER PT J AU Kim, MK Song, BJ Seidel, J Soh, Y Jeong, KS Green, MV Carrasquillo, JA Paik, CH AF Kim, MK Song, BJ Seidel, J Soh, Y Jeong, KS Green, MV Carrasquillo, JA Paik, CH TI Use of Tc-99m-MAG3-biocytin hepatobiliary scintigraphy to study the protective effect of synthetic enzyme inhibitors on CCL4-induced hepatotoxicity. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 796 EP 796 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000702 ER PT J AU Kobayashi, H Wu, C Yoo, TM Sun, BF Pastan, I Paik, CH Gansow, OA Carrasquillo, JA Brechbiel, MW AF Kobayashi, H Wu, C Yoo, TM Sun, BF Pastan, I Paik, CH Gansow, OA Carrasquillo, JA Brechbiel, MW TI Evaluation of the stability and in vivo biodistribution of isomers of CHX-DTPA for yttrium labeling of monoclonal antibodies. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 824 EP 824 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000730 ER PT J AU Pavel, DG VanHorn, JD AF Pavel, DG VanHorn, JD TI Evaluating the significance of changes in brain SPECT SO JOURNAL OF NUCLEAR MEDICINE LA English DT Letter C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892. NIMH,PET UNIT,CLIN BRAIN DISORDERS BRANCH,BETHESDA,MD 20892. RP Pavel, DG (reprint author), UNIV ILLINOIS,MED CTR,CHICAGO,IL 60680, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 BP 828 EP 829 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WX896 UT WOS:A1997WX89600046 PM 9170458 ER PT J AU Seidel, J Siegel, S Gandler, WR Green, MV AF Seidel, J Siegel, S Gandler, WR Green, MV TI Accuracy of event positioning in a pixelated BGO array coupled to a miniature position-sensitive phototube. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 842 EP 842 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000748 ER PT J AU DaubeWitherspoon, ME Green, SL Plascjak, P Wu, C Carson, RE Brechbiel, M Eckelman, WC AF DaubeWitherspoon, ME Green, SL Plascjak, P Wu, C Carson, RE Brechbiel, M Eckelman, WC TI PET imaging characteristics of Ga-66. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. NIH,PET DEPT,BETHESDA,MD 20892. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 856 EP 856 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000762 ER PT J AU Herscovitch, P Schmall, B Doudet, DJ Carson, RE Eckelman, WC AF Herscovitch, P Schmall, B Doudet, DJ Carson, RE Eckelman, WC TI Biodistribution and radiation dose estimates for [C-11]raclopride SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,PET DEPT,BETHESDA,MD 20892. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 951 EP 951 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000857 ER PT J AU Kobayashi, H Sun, BF Yoo, TM Kim, MK Le, N Wang, QC Pastan, I Waldmann, TA Paik, CH Carrasquillo, JA AF Kobayashi, H Sun, BF Yoo, TM Kim, MK Le, N Wang, QC Pastan, I Waldmann, TA Paik, CH Carrasquillo, JA TI Comparison of two methods to avoid the adverse effects of circulating antigen on biodistribution of I-125 anti-Tac dsFv: Preinjection of IgG vs clearance of antigen with avidin-biotin system. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 980 EP 980 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000886 ER PT J AU Lang, L Jagoda, E Green, S Pastan, I Aloj, L Gallo, M Seidel, J Green, MV DaubeWitherspoon, ME Eckelman, WC AF Lang, L Jagoda, E Green, S Pastan, I Aloj, L Gallo, M Seidel, J Green, MV DaubeWitherspoon, ME Eckelman, WC TI Altering the kinetics of 4-[F-18]fluoro benzoyl (FB) anti-Tac dsFv fragment in the kidney. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,DEPT NUCL MED,PET DEPT,BETHESDA,MD. NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 985 EP 985 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000891 ER PT J AU Jagoda, E Aloj, L Seidel, J Lang, L Moody, T Green, S Carcao, C Witherspoon, MD Green, MV Eckelman, WC AF Jagoda, E Aloj, L Seidel, J Lang, L Moody, T Green, S Carcao, C Witherspoon, MD Green, MV Eckelman, WC TI The biodistribution of a F-18 labeled derivative of vasoactive intestinal peptide (dVIP) in a xenograft mouse model of breast cancer. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,CTR CLIN,POSITRON EMISS TOMOG DEPT,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT NUCL MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 1012 EP 1012 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000918 ER PT J AU Caraco, C Aloj, L Eckelman, WC AF Caraco, C Aloj, L Eckelman, WC TI Retention of FDG in cancer cells: The role of glucose-6-phosphatase. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,CTR CLIN,PET DEPT,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT NUCL MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 1048 EP 1048 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000954 ER PT J AU Kobayashi, H Sun, BF Yoo, TM Hun, ES Kim, MK Le, N Wang, QC Nelson, DL Pastan, L Waldmann, TA Paik, CH Carrasquillo, JA AF Kobayashi, H Sun, BF Yoo, TM Hun, ES Kim, MK Le, N Wang, QC Nelson, DL Pastan, L Waldmann, TA Paik, CH Carrasquillo, JA TI Epitope coating of circulating antigen: Positive and negative effect of two antibodies recognizing different epitopes of the alpha subunit of the IL-2 receptor on the biodistribution of I-125 anti-Tac dsFv. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 1065 EP 1065 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000971 ER PT J AU Kim, MK Seidel, J Le, N Kim, IS Yao, TM Barker, C Kobayashi, H Green, MV Carrasquillo, JC Paik, CH AF Kim, MK Seidel, J Le, N Kim, IS Yao, TM Barker, C Kobayashi, H Green, MV Carrasquillo, JC Paik, CH TI Differential diagnosis of CCl4-induced hepatitis from alpha-naphthylisothiocyanate-induced cholestasis using Tc-99m-mercaptoacetyltriglycine (MAG3)-biocytin hepato-biliary scintigraphy. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 1072 EP 1072 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98000978 ER PT J AU Chefer, SI Morris, ED Wong, DF Ingram, DK Roth, G Lane, M Muzic, RF Grant, S Weyl, L Matochik, J Villemagne, V Yokoi, F Dannals, RF London, ED AF Chefer, SI Morris, ED Wong, DF Ingram, DK Roth, G Lane, M Muzic, RF Grant, S Weyl, L Matochik, J Villemagne, V Yokoi, F Dannals, RF London, ED TI Considerations for measuring dopamine binding potential with PET in the striata of primates smaller than humans. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NATL INST DRUG ABUSE,LEXINGTON,KY. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. NIA,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 1141 EP 1141 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98001047 ER PT J AU Lee, KS Schieck, C Glennon, RA Jones, DW Gorey, JG Knable, MB Coppola, RC Heinz, A Weinberger, DR AF Lee, KS Schieck, C Glennon, RA Jones, DW Gorey, JG Knable, MB Coppola, RC Heinz, A Weinberger, DR TI Synthesis of a novel radioiodinated 5-HT2 analog for SPECT imaging of serotonin receptors. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIMH,CBDB,WASHINGTON,DC. VCU,MCV,SCH PHARM,DEPT MED CHEM,RICHMOND,VA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 1144 EP 1144 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98001050 ER PT J AU Pavel, DG Thompson, D Patel, B Lin, Q Brint, S Dujovny, M Ibanez, V AF Pavel, DG Thompson, D Patel, B Lin, Q Brint, S Dujovny, M Ibanez, V TI Evaluation of brain SPECT changes using statistic parametric mapping (SPM) following Diamox (D) challenge SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 UNIV ILLINOIS,MED CTR,CHICAGO,IL. NIA,NEUROSCI LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 1177 EP 1177 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98001083 ER PT J AU Heinz, A Bertolino, A Saunders, RC Kolachana, BS Jones, DW Gorey, JG Bachevalier, J Lee, KS Knable, MB Weinberger, DR AF Heinz, A Bertolino, A Saunders, RC Kolachana, BS Jones, DW Gorey, JG Bachevalier, J Lee, KS Knable, MB Weinberger, DR TI Frontal lobe dysfunction measured with SPECT, MRSI, and microdialysis in monkeys with neonatal mesial temporal lesions. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIMH,CTR NEUROSCI,WASHINGTON,DC 20032. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 1190 EP 1190 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98001096 ER PT J AU Carson, RE Kiesewetter, DO Jagoda, E Der, MG Herscovitch, P Eckelman, WC AF Carson, RE Kiesewetter, DO Jagoda, E Der, MG Herscovitch, P Eckelman, WC TI Competition studies of the muscarinic cholinergic ligand [F-18]FP-TZTP. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,PET DEPT,BETHESDA,MD 20892. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 1198 EP 1198 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98001104 ER PT J AU Jones, DW Heinz, A Gorey, JG Lee, KS Knable, MB Urbina, RA Weinberger, DR AF Jones, DW Heinz, A Gorey, JG Lee, KS Knable, MB Urbina, RA Weinberger, DR TI A simple, sensitive, and efficient method of directly determining plasma concentrations of free [I-123]beta-CIT at extended times by TLC of ultrafiltrates. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIMH,CTR NEUROSCI,WASHINGTON,DC 20032. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 1207 EP 1207 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98001113 ER PT J AU Yokoi, F Szymanski, S Offord, SJ Grunder, G Dogan, AS Ravert, HT Dannals, RF London, ED Gjedde, A Wong, DF AF Yokoi, F Szymanski, S Offord, SJ Grunder, G Dogan, AS Ravert, HT Dannals, RF London, ED Gjedde, A Wong, DF TI Effect of cholinesterase inhibitors on binding to nicotinic acetylcholine receptors in human brain: A PET comparison. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIDA,JOHNS HOPKINS MED INST,BALTIMORE,MD. HOECHEST MARION ROUSSEL,CINCINNATI,OH. AARHUS UNIV,DK-8000 AARHUS C,DENMARK. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 1215 EP 1215 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98001121 ER PT J AU Vera, DR Eckelman, WC AF Vera, DR Eckelman, WC TI Kinetic modeling of a multistep pretargeting protocol for PET-based radioimmunoimaging SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 UNIV CALIF DAVIS,MED CTR,DEPT RADIOL,SACRAMENTO,CA 95817. NIH,CTR CLIN,PET DEPT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 1301 EP 1301 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98001185 ER PT J AU Lee, KS Jones, DW Gorey, JG Knable, MB Coppola, RC Heinz, A Rice, KC Weinberger, DR AF Lee, KS Jones, DW Gorey, JG Knable, MB Coppola, RC Heinz, A Rice, KC Weinberger, DR TI Radiochemical yields of tri-methyl stannylated precursors and tri-n-butyl stannylated precursors. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIMH,CBDB,WASHINGTON,DC. NIDDKD,MED CHEM LAB,NIH,BETHESDA,MD 20892. NIDDKD,NEUROSCI LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1997 VL 38 IS 5 SU S BP 1313 EP 1313 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY980 UT WOS:A1997WY98001197 ER PT J AU BallardBarbash, R Birt, DF Kestin, M King, IB AF BallardBarbash, R Birt, DF Kestin, M King, IB TI Perspectives on integrating experimental and epidemiologic research on diet, anthropometry and breast cancer SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Diet, Anthropometry and Breast Cancer: Integration of Experimental and Epidemiologic Approaches given at Experimental Biology 96 CY APR 15, 1996 CL WASHINGTON, DC SP Amer Soc Nutr Sci DE animal disease models; biomarkers; breast cancer; dietary fat; weight ID BODY-FAT DISTRIBUTION; RISK; DISEASE; WOMEN; SIZE; MICE AB Three perspectives on the integration of experimental and epidemiologic research on diet, anthropometry and breast cancer are presented. I) Although body weight and height have been linked to breast cancer risk by epidemiologic research, their roles have not been directly explored with animal models. However, basic, clinical and epidemiologic research on obesity and associated metabolic alterations may be pertinent. Individual differences in the timing and magnitude of weight gain and loss during adult life need to be considered in epidemiologic studies of adiposity and breast cancer, along with individual differences in the pattern of body fat deposition, the hormonal and metabolic changes that accompany the adiposity, and family history of obesity-related chronic diseases. Animal models with genetic predispositions to obesity, diabetes and breast cancer merit further exploration, as well as models that can evaluate exposures occurring after puberty. 2) The synergy between experimental and epidemiologic studies on fat and energy intake and breast carcinogenesis has been productive because each discipline has had to incorporate recent findings of the other. Dietary studies utilizing animals with different genetic profiles are promising, but require identification of the critical genes in human carcinogenesis. 3) Controlled dietary intervention studies with human participants using intermediate endpoints can bridge the gap between animal and epidemiologic studies, but generally accepted intermediate endpoints for breast cancer need to be developed. Such studies would permit better control of diet than large clinical trials and the opportunity to explore mechanisms. C1 NCI,APPL RES BRANCH,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. UNIV NEBRASKA,MED CTR,EPPLEY INST RES CANC,OMAHA,NE 68698. FRED HUTCHINSON CANC RES CTR,CANC PREVENT RES PROGRAM,SEATTLE,WA 98104. NR 22 TC 9 Z9 9 U1 0 U2 3 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 1997 VL 127 SU 5 BP S936 EP S939 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WZ923 UT WOS:A1997WZ92300034 PM 9164268 ER PT J AU Dutta, C AF Dutta, C TI Significance of sarcopenia in the elderly SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Sarcopenia: Diagnosis and Mechanisms given at Experimental Biology 96 CY APR 17, 1996 CL WASHINGTON, DC SP Amer Soc Nutr Sci, Merck & Co DE sarcopenia; aging; muscle mass ID MUSCLE-CONTRACTION INCREASES; INSULIN-RESISTANCE; STRENGTH; WOMEN; FAT; MEN; RAT; PERFORMANCE; HUMANS; INVIVO AB At the present time, there is only limited understanding of the public health significance of sarcopenia. The well-recognized functional consequences of sarcopenia include gait and balance problems and increased risk for fall. Ultimately, these impairments can lead to the loss of physical functional independence. However, sarcopenia may also contribute to an increased risk for chronic diseases such as diabetes and osteoporosis. Future studies of the pathophysiologic significance of sarcopenia need to consider the contribution(s) of muscle properties (9.9., muscle fiber composition, muscle blood flow, fatigue characteristics, innervation) to alterations in physical performance, metabolism and physiology, and skeletal health. More comprehensive studies on the sequelae of sarcopenia are critical to an accurate assessment of the public health burden that sarcopenia poses to the elderly population. RP Dutta, C (reprint author), NIA,GERIATR PROGRAM,BETHESDA,MD 20893, USA. NR 23 TC 53 Z9 55 U1 0 U2 2 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 1997 VL 127 SU 5 BP S992 EP S993 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WZ923 UT WOS:A1997WZ92300048 PM 9164281 ER PT J AU Harris, T AF Harris, T TI Muscle mass and strength: Relation to function in population studies SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Sarcopenia: Diagnosis and Mechanisms given at Experimental Biology 96 CY APR 17, 1996 CL WASHINGTON, DC SP Amer Soc Nutr Sci, Merck & Co DE sarcopenia; muscle mass; aging ID GRIP STRENGTH; MEN; WOMEN; MOBILITY; ABILITY; PEOPLE AB The use of the term sarcopenia to describe the age-related loss in skeletal muscle and its functional consequences is relatively recent. However, interest in the relationship of muscle mass to strength and function predates the concept of sarcopenia as researchers have attempted to understand differences in mass and strength between men and women, young and old. Most of these studies are cross-sectional comparisons in which muscle mass and strength tend to be linearly related, so that those with more muscle tend to be stronger. This article focuses instead on some potential problems with the sarcopenia-function association in old age and presents what little data exist from longitudinal population studies addressing the effect of sarcopenia over time. RP Harris, T (reprint author), NIA,NIH,BETHESDA,MD 20892, USA. NR 17 TC 57 Z9 57 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 1997 VL 127 SU 5 BP S1004 EP S1006 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WZ923 UT WOS:A1997WZ92300051 ER PT J AU Rao, GN AF Rao, GN TI New nonpurified diet (NTP-2000) for rodents in the national toxicology program's toxicology and carcinogenesis studies SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Animal Diets for Nutritional and Toxicological Research at Experimental Biology 96 CY APR 15, 1996 CL WASHINGTON, DC SP Amer Soc Nutr Sci, Natl Canc Inst, Int Life Sci Inst DE protein; fat; fiber; lesions; rats ID FISCHER-344 RATS AB The NIH-07 open-formula nonpurified diet was the selected diet for rodents in the National Toxicology Program's toxicology and carcinogenesis studies from 1980 to 1994. Protein and mineral concentrations of the NIH-07 diet may have increased some diet- and age-associated lesions such as nephropathy. A number of experimental nonpurified diets with lower protein and higher fat and fiber (similar to 15% protein, 7-8.5% fat, and 9-14% crude fiber) than the NIH-07 diet were formulated and evaluated in Fischer 344 (F344) rats. Decreasing protein content of the diet decreased protein consumption by similar to 30% and decreased severity of nephropathy without affecting growth. Increased fat intake seemed to have decreased the incidence or severity of leukemia, a lethal neoplasm of F344 rats. Increasing fiber content without decreasing the caloric density lowered body weight gain and slowed growth of mammary tumors. Higher fat and/or fiber intake decreased the incidences of adrenal pheochromocytomas and medullary hyperplasia in male rats. Nonpurified diets with lower protein and higher fat and fiber concentrations than the NIH-07 diet decreased or delayed diet- and age-associated lesions and increased survivals in 2-y studies. On the basis of these results, a new cereal-based nonpurified diet, designated as NTP-2000, was formulated with similar to 14.5% protein, similar to 8.2% fat, similar to 9.3% fiber and a calcium:phosphorus molar ratio of similar to 1.3. The NTP-2000 diet was compared with the NIH-07 diet in a 13-wk study in F344 rats. The NTP-2000 diet was adequate for growth, did not affect the hematological parameters and did not cause substantial changes in blood chemistry, serum enzyme or serum electrolyte values. The NTP-2000 diet decreased liver and kidney weights, prevented nephrocalcinosis and decreased the severity of diet- and possibly age-associated lesions. RP Rao, GN (reprint author), NIEHS,NATL TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 22 TC 37 Z9 37 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 1997 VL 127 SU 5 BP S842 EP S846 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WZ923 UT WOS:A1997WZ92300014 PM 9164250 ER PT J AU Thurman, RG Bradford, BU Iimuro, Y Knecht, KT Connor, HD Adachi, Y Wall, C Arteel, GE Raleigh, JA Forman, DT Mason, RP AF Thurman, RG Bradford, BU Iimuro, Y Knecht, KT Connor, HD Adachi, Y Wall, C Arteel, GE Raleigh, JA Forman, DT Mason, RP TI Role of Kupffer cells, endotoxin and free radicals in hepatotoxicity due to prolonged alcohol consumption: Studies in female and male rats SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Nutritional Factors and Oxidative Stress in Experimental Alcoholic Liver Disease at Experimental Biology 96 CY APR 15, 1996 CL WASHINGTON, DC SP Amer Soc Nutr Sci DE alcohol-induced liver injury; endotoxin; free radicals; sex differences; rats ID PERICENTRAL REGIONS; SWIFT INCREASE; LIVER-INJURY; ETHANOL; METABOLISM; EXPOSURE; HYPOXIA; DISEASE; LOBULE AB Alcohol ingestion results in increases in the release of endotoxin from gut bacteria or membrane permeability of the gut to endotoxin, or both. Female rats are more sensitive to these changes. Elevated levels of endotoxin activate Kupffer cells to release substances such as eicosanoids, tumor necrosis factor-alpha and free radicals. Prostaglandins increase oxygen uptake and most likely are responsible for the hypermetabolic state in the liver. The increase in oxygen demand leads to hypoxia in the liver, and on reperfusion, alpha-hydroxyethyl free radicals are formed that lead to tissue damage in oxygen-poor pericentral regions of the liver lobule. C1 UNIV N CAROLINA,DEPT RADIAT ONCOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT PATHOL & LAB MED,CHAPEL HILL,NC 27599. NIEHS,MOL BIOPHYS LAB,NIH,RES TRIANGLE PK,NC 27709. RP Thurman, RG (reprint author), UNIV N CAROLINA,DEPT PHARMACOL,HEPATOBIOL & TOXICOL LAB,1124 FAC LAB OFF BLDG,CB 7365,CHAPEL HILL,NC 27599, USA. FU NIAAA NIH HHS [AA-09156, AA-03626] NR 30 TC 22 Z9 24 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 1997 VL 127 SU 5 BP S903 EP S906 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WZ923 UT WOS:A1997WZ92300026 PM 9164260 ER PT J AU Ziegler, RG AF Ziegler, RG TI Anthropometry and breast cancer SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Diet, Anthropometry and Breast Cancer: Integration of Experimental and Epidemiologic Approaches given at Experimental Biology 96 CY APR 15, 1996 CL WASHINGTON, D.C. SP Amer Soc Nutr Sci DE breast cancer; central adiposity; energy balance; height; weight ID BODY-FAT DISTRIBUTION; RISK; WOMEN; WEIGHT; HEIGHT; SIZE; MASS; SURVIVAL; HORMONE; OBESITY AB Relatively consistent findings about the relationships between body size and shape and breast cancer risk have been emerging in recent years. Adult height is predictive of breast cancer risk, even in populations with no evidence of energy or nutrient deficiency. A complex relationship with adiposity has been observed. The dominant pattern is increasing risk with increasing adiposity except in younger, premenopausal women from countries with high breast cancer rates, in whom an inverse association is noted. When adult weight is evaluated as a dynamic measurement rather than a constant one, excess weight in the years preceeding breast cancer diagnosis seems especially critical, consistent with the substantial evidence that adiposity at the time of breast cancer diagnosis is associated with an increased probability of recurrence and a decreased survival time. Adult weight gain has consistently predicted increased risk of breast cancer in older, postmenopausal women, even in some studies in which adult adiposity was only weakly associated with risk. In several studies, women with increased abdominal fat deposition, or central adiposity, also had an elevated risk of postmenopausal, though not necessarily premenopausal, breast cancer, independent of their adult adiposity. These patterns suggest that lifestyles leading to a positive energy balance are involved in the etiology of this disease and that energy intake and physical activity may be especially influential. The hormonal and metabolic mechanisms that account for these relationships between body size and shape and breast cancer risk are not adequately understood and merit further study. RP Ziegler, RG (reprint author), NCI, NUTR EPIDEMIOL BRANCH, NIH, BETHESDA, MD 20892 USA. NR 26 TC 36 Z9 36 U1 0 U2 0 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 EI 1541-6100 J9 J NUTR JI J. Nutr. PD MAY PY 1997 VL 127 SU 5 BP S924 EP S928 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WZ923 UT WOS:A1997WZ92300031 PM 9164265 ER PT J AU Klein, S Kinney, J Jeejeebhoy, K Alpers, D Hellerstein, M Murray, M Twomey, P Bistrian, B Bothe, A Heitkemper, M Hubbard, V Schnackenberg, D Bernstein, E Hambidge, M Heymsfield, S IretonJones, C Wolfson, M Jacobs, D Keithley, J Meguid, M Pingleton, S Kopple, J Koretz, R Shulman, R Wilmore, D Driscoll, D Fleming, CR Greene, H Sitrin, M Herrmann, V Lipman, T Mock, D Borum, P Shronts, E AF Klein, S Kinney, J Jeejeebhoy, K Alpers, D Hellerstein, M Murray, M Twomey, P Bistrian, B Bothe, A Heitkemper, M Hubbard, V Schnackenberg, D Bernstein, E Hambidge, M Heymsfield, S IretonJones, C Wolfson, M Jacobs, D Keithley, J Meguid, M Pingleton, S Kopple, J Koretz, R Shulman, R Wilmore, D Driscoll, D Fleming, CR Greene, H Sitrin, M Herrmann, V Lipman, T Mock, D Borum, P Shronts, E TI Nutrition support in clinical practice: Review of published data and recommendations for future research directions SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Review ID TOTAL PARENTERAL-NUTRITION; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; SHORT BOWEL SYNDROME; CHAIN AMINO-ACIDS; BONE-MARROW TRANSPLANTATION; SEVERE ACUTE-PANCREATITIS; ACUTE-RENAL-FAILURE; DOUBLE-BLIND TRIAL; PERCUTANEOUS ENDOSCOPIC GASTROSTOMY; SUBJECTIVE GLOBAL ASSESSMENT AB In the last 30 years, marked advances in enteral feeding techniques, venous access, and enteral and parenteral nutrient formulations have made it possible to provide nutrition support to almost all patients. Despite the abundant medical Literature and widespread use of nutritional therapy, many areas of nutrition support remain controversial. Therefore, the leadership at the National Institutes of Health, The American Society for Parenteral and Enteral Nutrition, and The American Society for Clinical Nutrition convened an advisory committee to perform a critical review of the current medical literature evaluating the clinical use of nutrition support; the goal was to assess our current body of knowledge and to identify the issues that deserve further investigation. The panel was divided into five groups to evaluate the following areas: nutrition assessment, nutrition support in patients with gastrointestinal diseases, nutrition support in wasting diseases, nutrition support in critically ill patients, and perioperative nutrition support. The findings from each group are summarized in this report. This document is not meant to establish practice guidelines for nutrition support. The use of nutritional therapy requires a careful integration of data from pertinent clinical trials, clinical expertise in the illness or injury being treated, clinical expertise in nutritional therapy, and input from the patient and his/her family. C1 HARVARD UNIV,MED CTR,BETH ISRAEL DEACONESS MED CTR,BOSTON,MA 02115. UNIV CHICAGO,MED CTR,CHICAGO,IL 60637. UNIV WASHINGTON,SEATTLE,WA 98195. NIDDKD,BETHESDA,MD 20892. ASCN,BETHESDA,MD. ASPEN,SILVER SPRING,MD. ROCKEFELLER UNIV,NEW YORK,NY 10021. ST MICHAELS HOSP,TORONTO,ON M5B 1W8,CANADA. UNIV COLORADO,MED CTR,DENVER,CO 80202. ST LUKES ROOSEVELT HOSP,NEW YORK,NY 10025. CORAM HEALTHCARE,CARROLLTON,TX. BAXTER HEALTHCARE CORP,MCGAW PK,IL. SAN FRANCISCO VET ADM MED CTR,SAN FRANCISCO,CA. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL. SUNY HLTH SCI CTR,SYRACUSE,NY 13210. UNIV KANSAS,MED CTR,KANSAS CITY,KS 66103. MAYO CLIN,ROCHESTER,MN. HARBOR UCLA MED CTR,TORRANCE,CA 90509. OLIVE VIEW UCLA MED CTR,SYLMAR,CA 91342. BAYLOR COLL MED,HOUSTON,TX 77030. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. BETH ISRAEL DEACONESS MED CTR,BOSTON,MA. MAYO CLIN,JACKSONVILLE,FL 32224. SLIM FAST FOOD CO,W PALM BEACH,FL. UNIV CHICAGO,CHICAGO,IL 60637. UNIV CALIF BERKELEY,BERKELEY,CA 94720. ST LOUIS UNIV,SCH MED,ST LOUIS,MO. DEPT VET AFFAIRS MED CTR,WASHINGTON,DC. UNIV ARKANSAS MED SCI HOSP,LITTLE ROCK,AR 72205. UNIV FLORIDA,GAINESVILLE,FL. UNIV MINNESOTA,MINNEAPOLIS,MN. RP Klein, S (reprint author), WASHINGTON UNIV,SCH MED,660 S EUCLID AVE,BOX 8127,ST LOUIS,MO 63110, USA. NR 256 TC 224 Z9 245 U1 2 U2 5 PU AMER SOC PARENTERAL & ENTERAL NUTRITION PI SILVER SPRING PA 8630 FENTON STREET SUITE 412, SILVER SPRING, MD 20910 SN 0148-6071 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD MAY-JUN PY 1997 VL 21 IS 3 BP 133 EP 156 DI 10.1177/0148607197021003133 PG 24 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XA043 UT WOS:A1997XA04300002 PM 9168367 ER PT J AU Ogata, H Takeya, M Yoshimura, T Takagi, K Takahashi, K AF Ogata, H Takeya, M Yoshimura, T Takagi, K Takahashi, K TI The role of monocyte chemoattractant protein-1 (MCP-1) in the pathogenesis of collagen-induced arthritis in rats SO JOURNAL OF PATHOLOGY LA English DT Article DE monocytes; macrophages; monocyte chemoattractant protein; pathogenesis; arthritis; rat model ID RHEUMATOID-ARTHRITIS; MONOCLONAL-ANTIBODIES; II COLLAGEN; IMMUNOHISTOCHEMICAL ANALYSIS; MACROPHAGE SUBPOPULATIONS; TYPE-2 COLLAGEN; LYMPHOCYTES-T; EXPRESSION; CELLS; POPULATIONS AB Collagen-induced arthritis was produced in rats by intradermal immunization with type II collagen and the expression and production of monocyte chemoattractant protein-1 (MCP-1) were examined by immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and Northern blot analysis. Two to three weeks after the immunization, the hindfeet showed swelling and redness, followed by the development of severe arthritis, particularly in the ankle joints. During this period, prominent infiltration of neutrophils and macrophages was observed. Sandwich ELISA and Northern blot analysis revealed that MCP-1 concentrations in the joint lavages and MCP-1 mRNA levels in the joint tissues both peaked at 2 weeks after the immunization. By immunohistochemistry, various types of cells, particularly neutrophils, macrophages, synovial cells, and vascular endothelial cells, stained positively for MCP-1. Finally, injection of a neutralizing monoclonal antibody against rat MCP-1 significantly decreased the number of exudate macrophages in the lesions and reduced the ankle swelling by about 30 per cent compared with controls. These results suggest that MCP-1 plays a critical role in this model in the recruitment of monocytes and in the development of arthritis. (C) 1997 by John Wiley & Sons, Ltd. C1 KUMAMOTO UNIV,SCH MED,DEPT PATHOL 2,KUMAMOTO 860,JAPAN. KUMAMOTO UNIV,SCH MED,DEPT ORTHOPED SURG,KUMAMOTO 860,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,IMMUNOPATHOL SECT,FREDERICK,MD 21701. NR 34 TC 130 Z9 134 U1 0 U2 7 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0022-3417 J9 J PATHOL JI J. Pathol. PD MAY PY 1997 VL 182 IS 1 BP 106 EP 114 PG 9 WC Oncology; Pathology SC Oncology; Pathology GA XC280 UT WOS:A1997XC28000016 PM 9227349 ER PT J AU Novakovic, B Fears, TR Horowitz, ME Tucker, MA Wexler, LH AF Novakovic, B Fears, TR Horowitz, ME Tucker, MA Wexler, LH TI Late effects of therapy in survivors of Ewing's sarcoma family tumors SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE Ewing's sarcoma family tumors; late effects of therapy ID COMBINED MODALITY THERAPY; LONG-TERM SURVIVORS; CHILDHOOD-CANCER SURVIVORS; ADOLESCENT CANCER; YOUNG-ADULTS; MALIGNANT-TUMORS; FOLLOW-UP; BONE; FERTILITY; PREGNANCY AB Purpose: This late effects study was designed to determine if survivors of Ewing's sarcoma family tumors (ESFT) had adverse outcomes in employment, marital status, fertility, and functional status when compared to sibling controls. Subjects and methods: Eighty-nine survivors (case subjects) of ESFT treated at the National Cancer Institute between 1965 and 1992 and 97 sibling controls completed a questionnaire probing aspects of quality of life. The answers from case subjects were compared to pooled and matched sibling controls for all key variables. Odds ratios (OR) and p values from pooled analyses are presented. Results: Although case subjects and controls did not differ in educational achievement, case subjects wen less likely to be employed full-time (OR 0.4, p<0.01), to be married (OR 0.2, p<0.01), and to have children (OR 0.3, p<0.01). Their most common treatment-related difficulties included permanent hair and skin changes (43%), lung problems (18%), neurologic problems (14%), visual difficulties (10%), second malignancy (7%), and amputation (5%). Functional status, measured by Karnofsky performance scale, was also adversely affected in case subjects. Case subjects did not differ from sibling controls in health care insurance status or in utilization of health services. Conclusions: important aspects of life such as employment, marital status, fertility, and functional status are affected in survivors of ESFT. More studies are needed to better define the health status of adult survivors of pediatric cancer and the impact of cancer in adolescence on psychosocial development. C1 NATL CANC INST,GENET EPIDEMIOL BRANCH,BETHESDA,MD. NATL CANC INST,BIOSTAT BRANCH,BETHESDA,MD. NATL CANC INST,PEDIAT BRANCH,BETHESDA,MD. TEXAS CHILDRENS HOSP,HOUSTON,TX 77030. BAYLOR COLL MED,HOUSTON,TX 77030. COLUMBIA PRESBYTERIAN MED CTR,NEW YORK,NY 10032. RI Tucker, Margaret/B-4297-2015 NR 28 TC 43 Z9 44 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD MAY-JUN PY 1997 VL 19 IS 3 BP 220 EP 225 DI 10.1097/00043426-199705000-00008 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA XF157 UT WOS:A1997XF15700008 PM 9201144 ER PT J AU Zhou, LX Erickson, RR Hardwick, JP Park, SS Wrighton, SA Holtzman, JL AF Zhou, LX Erickson, RR Hardwick, JP Park, SS Wrighton, SA Holtzman, JL TI Catalysis of the cysteine conjugation and protein binding of acetaminophen by microsomes from a human lymphoblast line transfected with the cDNAs of various forms of human cytochrome P450 SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID REACTIVE METABOLITE FORMATION; PARA-BENZOQUINONE IMINE; RAT-LIVER; MONOCLONAL-ANTIBODIES; HEPATIC MICROSOMES; ACTIVATION; ETHANOL; HEPATOCYTES; INHIBITORS; OXIDATION AB We have previously found that for acetaminophen kinetic differences exist between the hepatic microsomal catalyzed protein binding and cysteine conjugation. We have also observed that the protein binding of acetaminophen is only to intralumenal proteins. Together these data suggested that two pools of the reactive metabolite, N-acetyl-p-benzoquinone imine (NABQI), are formed during the oxidative metabolism of acetaminophen: one on the cytosolic surface and the other within the lumen of the microsomes. This would indicate that some of forms of cytochrome P450 (CYP) catalyzing NABQI formation have their active site on the cytosolic surface and others on the lumenal surface. We have examined this question by comparing the rates of cysteine conjugation and protein binding of acetaminophen by microsomes from lymphoblasts tranfected with the cDNAs for human CYPs. We found that CYP2D6 catalyzed only cysteine conjugation; CYP1A2 and 3A4 catalyzed only protein binding; CYP2E1 catalyzed both; and CYP1A1, CYP2A6 and CYP2B6 catalyzed neither. These data suggest that CYP2D6 has its active site only on the cytosolic surface; CYP1A2 and CYP3A4 only on the lumenal surface; and CYP2E1 has catalytic sites on both the lumenal and cytosolic surfaces of the membrane. In mouse studies we have found that ethanol administration increased acetaminophen protein binding by 265% but cysteine conjugation by only 61%. CYP2E1 and CYP2B increased, whereas CYP3A decreased and the others did not change. These data suggest that in control mice CYP2E1 catalyzes the bulk of protein binding, whereas CYP2D catalyzes slightly more cysteine conjugation than does CYP2E1. C1 VET AFFAIRS MED CTR,SECT THERAPEUT 111T,MED SERV,MINNEAPOLIS,MN 55417. VET AFFAIRS MED CTR,RES SERV,MINNEAPOLIS,MN 55417. UNIV MINNESOTA,DEPT PHARMACOL,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,DEPT MED,MINNEAPOLIS,MN 55455. NE OHIO UNIV,COLL MED,ROOTSTOWN,OH 44272. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. ELI LILLY & CO,INDIANAPOLIS,IN 46285. FU NIEHS NIH HHS [R01 ES 03731] NR 32 TC 19 Z9 19 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 1997 VL 281 IS 2 BP 785 EP 790 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WX658 UT WOS:A1997WX65800024 PM 9152386 ER PT J AU Ambudkar, IS Wu, AJ Meehan, S AF Ambudkar, IS Wu, AJ Meehan, S TI IFN-gamma-induced decrease in SERCA protein and depletion of intracellular calcium store(s) is associated with loss of cell growth and apoptosis in a human submandibular gland cell line SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Meeting Abstract C1 NIDR,SECRETORY PHYSIOL SECT,GENE THERAPY & THERAPEUT BRANCH,NIH,BETHESDA,MD 20892. NR 2 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD MAY PY 1997 VL 501P SI SI BP P157 EP P157 PG 1 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA XD091 UT WOS:A1997XD09100219 ER PT J AU Hunyady, B Hoffman, BJ Eisenhofer, G Hansson, SR Mezey, E AF Hunyady, B Hoffman, BJ Eisenhofer, G Hansson, SR Mezey, E TI Dopaminergic characteristics of isolated parietal cells from rats SO JOURNAL OF PHYSIOLOGY-PARIS LA English DT Article; Proceedings Paper CT 4th Congress of the International-Brain-Gut-Society CY SEP 18-20, 1996 CL PECS, HUNGARY SP Int Brain Gut Soc DE dopamine; gastrointestinal system; parietal cell; cell isolation; immunocytochemistry ID GASTRIC-ACID SECRETION; RECEPTOR ANTAGONIST; MUCOSAL INJURY; SYSTEM; AGONISTS; NEURONS; GUT; CATECHOLAMINES; IDENTIFICATION; ANTIBODIES AB Recently we have identified a dopamine-producing system in the gastric mucosa of rats. All the available morphological data suggest that parietal cells synthesize dopamine. In the present study we investigated the dopaminergic characteristics of isolated parietal cells by different methods. Mixed gastric mucosal cells were isolated and size-fractionated by elutriation. The proportion of neurons, parietal and endocrine cells in the fractions were determined by immunocytochemistry (ICC) using antibodies to neurofilament, proton pump and chromogranin A, respectively. No neurons were found in any of the cell preparations, while 56% parietal cell and 0.0% endocrine cell were achieved in the parietally enriched fraction. By Western blot, a tyrosine hydroxylase (TH, the rate-limiting enzyme of the catecholamine synthesis) immunoreactive protein species was demonstrated in isolated mucosal cells, comigrating with the TH immunoreactivity from PC12 cells. The TH immunoreactivity was colocalized to parietal cells by ICC. Dopamine transporter (DAT), a regulator of extracellular/intracellular dopamine balance in the nervous system, was also demonstrated in parietal cells. A significant amount of dopamine and DOPA were measured by HPLC (13.4 and 9.57 pg/10(6) cell, respectively) in parietally enriched cell fraction. Since this enriched cell fraction was virtually clear of both neurons and endocrine cells, demonstration of TH enzyme, DAT and dopamine in this fraction confirms that the parietal cell. population might be a major source of dopamine in the rat stomach, supporting our previous results achieved using whole tissue samples. C1 NINDS, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. NIMH, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Med Univ Pecs, Dept Med 1, H-7643 Pecs, Hungary. RP Mezey, E (reprint author), NINDS, Clin Neurosci Branch, NIH, Bldg 36,Room 3A17,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 44 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0928-4257 EI 1769-7115 J9 J PHYSIOL-PARIS JI J. Physiol.-Paris PD MAY-OCT PY 1997 VL 91 IS 3-5 BP 247 EP 256 DI 10.1016/S0928-4257(97)89493-4 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA YW745 UT WOS:000071968900022 PM 9403803 ER PT J AU Svikis, D Henningfield, J Gazaway, P Huggins, G Sosnow, K Hranicka, J Harrow, C Pickens, R AF Svikis, D Henningfield, J Gazaway, P Huggins, G Sosnow, K Hranicka, J Harrow, C Pickens, R TI Tobacco use for identifying pregnant women at risk of substance abuse SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article; Proceedings Paper CT 1st Annual Meeting of the Society-for-Research-on-Nicotine-and-Tobacco CY MAR, 1995 CL SAN DIEGO, CA SP Soc Res Nicotine & Tobacco DE smoking; pregnancy; substance abuse detection ID DRUG-USE; ALCOHOL; QUESTIONNAIRE; DEPENDENCE AB OBJECTIVE: To examine the effectiveness of current smoking status as a rapid screening tool to identify pregnant women at risk of heavy alcohol and/or illicit drug use. STUDY DESIGN: Women (N=92) seeking prenatal care were interviewed to assess lifetime and recent tobacco, alcohol and illicit drug use. Rates of recent heavy alcohol and illicit drug use were compared in current smokers and nonsmokers. RESULTS: All subjects reporting recent heavy alcohol and/or illicit drug use were current smokers; none were nonsmokers. CONCLUSION: Obstetric screening of pregnant women for current smoking status seems to be a cost-effective method of identifying those at risk of antepartum heavy alcohol and/or illicit drug use. C1 JOHNS HOPKINS UNIV, SCH MED, DEPT PSYCHIAT & BEHAV SCI, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT OBSTET & GYNECOL, BALTIMORE, MD 21205 USA. NATL INST DRUG ABUSE, INTRAMURAL RES PROGRAM, BALTIMORE, MD USA. RP Svikis, D (reprint author), JOHNS HOPKINS BAYVIEW MED CTR, CTR ADDICT & PREGNANCY, D-3 E, 4940 EASTERN AVE, BALTIMORE, MD 21224 USA. FU NIDA NIH HHS [P50 DA 09258] NR 18 TC 14 Z9 14 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 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD MAY PY 1997 VL 42 IS 5 BP 299 EP 302 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XB108 UT WOS:A1997XB10800010 PM 9172121 ER PT J AU Klippel, JH AF Klippel, JH TI Systemic lupus erythematosus: Demographics, prognosis, and outcome SO JOURNAL OF RHEUMATOLOGY LA English DT Article; Proceedings Paper CT Symposium on The Role of Hematopoietic Stem Cell Transplantation for Autoimmune Diseases CY OCT 27, 1995 CL FRED HUTCHINSON CANC RES CTR, SEATTLE, WA HO FRED HUTCHINSON CANC RES CTR DE systemic lupus erythematosus; prognosis; demographics ID ANTI-DNA AUTOANTIBODIES; PULSE CYCLOPHOSPHAMIDE; EMERGING CONCEPTS; DISEASE-ACTIVITY; RENAL-DISEASE; NEPHRITIS; SURVIVAL; MORTALITY; GENES AB Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder with an annual incidence of 50 to 70/million and a prevalence of 500/million population. The highest incidence is observed in women aged 20 to 40 years. The clinical manifestations of SLE are remarkably heterogeneous. Major organ system involvement may occur in the heart, lungs, kidneys, and central nervous system and is responsible for most of the mortality and morbidity caused by the disease. Complications of drug treatment, in particular corticosteroid side effects, contribute to longterm morbidity. The major causes of death are directly related to the disease and include acute vascular neurologic events, renal failure, cardiovascular or pulmonary involvement, infection, and coronary artery disease. RP Klippel, JH (reprint author), NIAMSD,NIH,BLDG 10,ROOM 9 S 205,BETHESDA,MD 20892, USA. NR 44 TC 26 Z9 27 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAY PY 1997 VL 24 SU 48 BP 67 EP 71 PG 5 WC Rheumatology SC Rheumatology GA WZ918 UT WOS:A1997WZ91800013 ER PT J AU Haynie, DL Alexander, C Walters, SR AF Haynie, DL Alexander, C Walters, SR TI Considering a decision-making approach to youth violence prevention programs SO JOURNAL OF SCHOOL HEALTH LA English DT Article AB The unfortunate exception to a general downturn in violent crime involves an upsurge in violence among youth. Violence often results when minor confrontations escalate. As school violence increasingly has become widespread, schools have become the location of many violence prevention efforts, few of which have been evaluated adequately. This paper focuses on enhancing decision-making skills as one approach to increase adolescents' ability to manage interpersonal violence. Adolescents can be considered fairly skilled decision-makers and their unique perspective must be considered in development of effective intervention programs. Data from a pilot study were examined for insights about adolescents' ability to make decisions in situations of interpersonal conflict. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,CTR ADOLESCENT HLTH PROMOT & DIS PREVENT,BALTIMORE,MD 21205. RP Haynie, DL (reprint author), NICHHD,PREVENT RES BRANCH,DIV EPIDEMIOL STAT & PREVENT RES,NIH,6100 EXECUT BLVD,ROOM 7B05,ROCKVILLE,MD 20892, USA. OI Haynie, Denise/0000-0002-8270-6079 NR 27 TC 7 Z9 7 U1 0 U2 0 PU AMER SCHOOL HEALTH ASSOC PI KENT PA PO BOX 708, KENT, OH 44240 SN 0022-4391 J9 J SCHOOL HEALTH JI J. Sch. Health PD MAY PY 1997 VL 67 IS 5 BP 165 EP 170 PG 6 WC Education & Educational Research; Education, Scientific Disciplines; Health Care Sciences & Services; Public, Environmental & Occupational Health SC Education & Educational Research; Health Care Sciences & Services; Public, Environmental & Occupational Health GA XE023 UT WOS:A1997XE02300001 PM 9210100 ER PT J AU Reynolds, TH Frye, PA Sforzo, GA AF Reynolds, TH Frye, PA Sforzo, GA TI Resistance training and the blood lactate response to resistance exercise in women SO JOURNAL OF STRENGTH AND CONDITIONING RESEARCH LA English DT Article DE weight lifting; exertion; cardiovascular ID HEART-RATE; PERFORMANCE; VOLUME; MEN AB This study examined the effect of resistance training on blood lactate (BL), heart rate (HR), and rating of perceived exertion (RPE) responses to an exhaustive set of squats in 7 college-age women. Baseline testing consisted of a dual set of squats at 70 and 50% of 1-RM performed to exhaustion. Immediate postexercise BL response was elevated 6.5-fold above baseline values while HR exceeded 90% of age-predicted max. After 10 wks of resistance training, the dependent variables were assessed at Post 1 and Post 2 testing sessions. At Post 1, subjects performed a nonexhaustive set of squats using the same workload and number of repetitions completed during baseline testing. At Post 2 they performed an exhaustive set of squats at 70 and 50% of posttraining 1-PM. Immediate postexercise BL was reduced at Post 1 when compared to baseline BL. Post-2 BL was similar to baseline BL and significantly greater than Post-1 BL. Resistance training also lowered the RPE response to resistance exercise at Post 1 (p less than or equal to 0.01), but Post-2 RPE did not differ from baseline values. The HR response to resistance exercise was not altered by resistance training. C1 NIH,BETHESDA,MD 20892. WESTERN MICHIGAN UNIV,DEPT HPER,KALAMAZOO,MI 49008. RP Reynolds, TH (reprint author), ITHACA COLL,DEPT EXERCISE & SPORT SCI,ITHACA,NY 14850, USA. NR 25 TC 5 Z9 5 U1 0 U2 2 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, CHAMPAIGN, IL 61820-2200 SN 1064-8011 J9 J STRENGTH COND RES JI J. Strength Cond. Res. PD MAY PY 1997 VL 11 IS 2 BP 77 EP 81 PG 5 WC Sport Sciences SC Sport Sciences GA WW573 UT WOS:A1997WW57300004 ER PT J AU Ohuoha, DC Maxwell, JA Thomson, LE Cadet, JL Rothman, RB AF Ohuoha, DC Maxwell, JA Thomson, LE Cadet, JL Rothman, RB TI Effect of dopamine receptor antagonists on cocaine subjective effects: A naturalistic case study SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE human; cocaine abuse; dopamine receptor antagonists ID VENTRAL TEGMENTAL AREA; SCHIZOPHRENIC-PATIENTS; NONHUMAN-PRIMATES; ABUSE; RATS; BEHAVIOR; REINFORCEMENT; STIMULANT; NEUROLEPTICS; INJECTIONS AB Schizophrenic patients on neuroleptic medications abuse cocaine and report cocaine-induced euphoria. This study was undertaken to provide better clinical characterization of these phenomena by administering the POMS and a custom-designed questionnaire. A group of heavy cocaine users who were nor mentally ill served as the control group. The results clearly suggest that schizophrenic patients report cocaine-induced euphoria and post-use craving despite being treated with therapeutic doses of haloperidol or fluphenazine. The responses of the control group were similar to that of the schizophrenic group except that the latter subjects reported a greater degree of anxiety. These results suggest that blockade of D2 receptors is not sufficient to block cocaine-induced subjective effects in humans. (C) 1997 Elsevier Science Inc. C1 ST ELIZABETH HOSP,ACUTE CARE HOSP,WASHINGTON,DC 20032. NIDA,MOL NEUROPSYCHIAT SECT,DIR,ADDICT RES CTR,NIH,BALTIMORE,MD 21124. RP Ohuoha, DC (reprint author), ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,POB 5180,BALTIMORE,MD 21124, USA. NR 42 TC 36 Z9 36 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD MAY-JUN PY 1997 VL 14 IS 3 BP 249 EP 258 DI 10.1016/S0740-5472(96)00161-4 PG 10 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA XV322 UT WOS:A1997XV32200004 PM 9306300 ER PT J AU Kane, JM Shears, LL Hierholzer, C Ambs, S Billiar, TR Posner, MC AF Kane, JM Shears, LL Hierholzer, C Ambs, S Billiar, TR Posner, MC TI Chronic hepatitis C virus infection in humans: Induction of hepatic nitric oxide synthase and proposed mechanisms for carcinogenesis SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Association-for-Academic-Surgery CY NOV 13-16, 1996 CL CHICAGO, IL SP Assoc Acad Surg ID CANCER; P21 AB Chronic inflammatory states frequently lead to the increased production of nitric oxide (NO) via inducible NO synthase (NOS-2). In addition, NO may produce mutagenesis through several mechanisms such as DNA oxidation, DNA deamination, and the formation of N-nitroso compounds. As there is a strong association between human hepatitis C virus (HCV) infection and the development of hepatocellular carcinoma (HCC), we were interested in whether human HCV hepatitis leads to induction of NOS-2 and if the mutation repair system of p53/p21 was unregulated. Reverse transcriptase-polymerase chain reaction (RTPCR) for human NOS-2 message was performed on RNA samples from both liver biopsies and whole liver from HCV-positive and control patients (normal liver from hepatic resections for metastases), Immunohistochemistry (IHC) for p53 and Western blot analysis for p21 were also performed on the whole liver samples. From the liver biopsies, 60% of HCV-positive patients expressed NOS-2 by RT-PCR. Looking at the whole liver samples, 100% of the HCV-positive patients expressed NOS-2 vs 12.5% in the normal samples. p53 was not detected in either group but there was upregulation of p21 over baseline expression in a number of the HCV-positive patients. Human HCV hepatitis leads to consistent upregulation of hepatic NOS-2 message, but message is not predictably present in ''normal'' human liver. There is also induction of p21 in some patients with HCV hepatitis. Chronic expression of NO in HCV hepatitis may play a role in DNA mutagenesis and the development of HCC. (C) 1997 Academic Press. C1 NIH,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. UNIV CHICAGO,DEPT SURG,CHICAGO,IL 60637. RP Kane, JM (reprint author), UNIV PITTSBURGH,DEPT SURG,497 SCAIFE HALL,PITTSBURGH,PA 15261, USA. NR 19 TC 49 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 0022-4804 J9 J SURG RES JI J. Surg. Res. PD MAY PY 1997 VL 69 IS 2 BP 321 EP 324 DI 10.1006/jsre.1997.5057 PG 4 WC Surgery SC Surgery GA XL453 UT WOS:A1997XL45300013 PM 9224400 ER PT J AU Castellanos, FX Giedd, JN Elia, J Marsh, WL Ritchie, GF Hamburger, SD Rapoport, JL AF Castellanos, FX Giedd, JN Elia, J Marsh, WL Ritchie, GF Hamburger, SD Rapoport, JL TI Controlled stimulant treatment of ADHD and comorbid Tourette's syndrome: Effects of stimulant and dose SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE methylphenidate; dextroamphetamine; tic disorders; double-blind clinical trial; attention-deficit/hyperactivity disorder ID DEFICIT HYPERACTIVITY DISORDER; TRICYCLIC ANTIDEPRESSANT TREATMENT; TIC DISORDERS; METHYLPHENIDATE TREATMENT; CHILDREN; CLONIDINE; DEXTROAMPHETAMINE; DESIPRAMINE; SYMPTOMS; GILLES AB Objective: To determine the effects of methylphenidate (MPH) and dextroamphetamine (DEX) on tic severity in boys with attention-deficit/hyperactivity disorder (ADHD) comorbid with Tourette's syndrome. Method: A g-week, placebo-controlled, double-blind crossover using a wide range of doses was completed by 20 subjects in three cohorts. Results: Relatively high doses of MPH and DEX in the first cohort produced significant increases in tic severity which were sustained on higher doses of DEX but which attenuated on MPH. Overall, 14 of 20 subjects continued stimulant treatment for 1 to 3 years, generally in combination with other psychotropics. Stimulant-associated adverse effects, including tic exacerbations, were reversible in all cases. Conclusion: A substantial minority of comorbid subjects had consistent worsening of ties on stimulants, although the majority experienced improvement in ADHD symptoms with acceptable effects on ties. MPH was better tolerated than DEX. C1 NIMH, CHILD PSYCHIAT BRANCH, BETHESDA, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Castellanos, Francisco/0000-0001-9192-9437 NR 44 TC 118 Z9 125 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 1997 VL 36 IS 5 BP 589 EP 596 DI 10.1097/00004583-199705000-00008 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA WV690 UT WOS:A1997WV69000008 PM 9136492 ER PT J AU Kumra, S Herion, D Jacobsen, LK Briguglia, C Grothe, D AF Kumra, S Herion, D Jacobsen, LK Briguglia, C Grothe, D TI Case study: Risperidone-induced hepatotoxicity in pediatric patients SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE hepatotoxicity; risperidone; pediatric ID NONALCOHOLIC STEATOHEPATITIS; CHILDREN; SCHIZOPHRENIA; ADOLESCENTS; CHILDHOOD AB The purpose of this case study is to document hepatic adverse effects associated with long-term risperidone use in pediatric populations. Charts of all patients admitted to the National Institute of Mental Health (NIMH) from December 1993 to April 1996 who had been treated with risperidone were screened for hepatotoxicity and weight gain. From the medical records of 13 psychotic children admitted to the NIMH and treated with risperidone, 2 children (both male) who presented with obesity, liver enzyme abnormalities, and confirmatory evidence of fatty liver were identified. In each case liver damage was reversed after discontinuation of risperidone and/or associated weight loss. The observations suggest that long-term risperidone therapy is possibly associated with hepatotoxicity in male pediatric patients. It is recommended that pediatric patients treated with risperidone have baseline liver function tests, careful monitoring of weight, and periodic monitoring of liver function tests during the maintenance phase of therapy. C1 NIMH,DEPT GASTROENTEROL,BETHESDA,MD 20892. NIMH,CLIN CTR PHARM,BETHESDA,MD 20892. RP Kumra, S (reprint author), NIMH,DEPT CHILD PSYCHIAT,10 CTR DR,ROOM 6N240,BETHESDA,MD 20892, USA. NR 23 TC 75 Z9 78 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 1997 VL 36 IS 5 BP 701 EP 705 DI 10.1097/00004583-199705000-00022 PG 5 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA WV690 UT WOS:A1997WV69000022 PM 9136506 ER PT J AU Slavkin, HC AF Slavkin, HC TI Diabetes, clinical dentistry and changing paradigms SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article RP Slavkin, HC (reprint author), NIDR,31 CTR DR,MSC 2290,BLDG 31,ROOM 2C39,BETHESDA,MD 20892, USA. NR 2 TC 6 Z9 9 U1 0 U2 1 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD MAY PY 1997 VL 128 IS 5 BP 638 EP 644 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA WY049 UT WOS:A1997WY04900027 PM 9150648 ER PT J AU Bidgood, WD Horii, SC Prior, FW VanSyckle, DE AF Bidgood, WD Horii, SC Prior, FW VanSyckle, DE TI Understanding and using DICOM, the data interchange standard for biomedical imaging SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Review ID EXPERIENCE; RADIOLOGY AB The Digital Imaging and Communications in Medicine (DICOM) Standard specifies a non-proprietary data interchange protocol, digital image format, and file structure for biomedical images and image-related information. The fundamental concepts of the DICOM message protocol, services, and information objects are reviewed as background for a detailed discussion of the functionality of DICOM; the innovations and limitations of the Standard; and the impact of various DICOM features on information system users. DICOM addresses five general application areas: (1) network image management, (2) network image interpretation management, (3) network print management, (4) imaging procedure management, (5) off-line storage media management. DICOM is a complete specification of the elements required to achieve a practical level of automatic interoperability between biomedical imaging computer systems-from application layer to bit-stream encoding. The Standard is being extended and expanded in modular fashion to support new applications and incorporate new technology. An interface to other Information Systems provides for shared management of patient, procedure, and results information related to images. A Conformance Statement template enables a knowledgeable user to determine if interoperability between two implementations is possible. Knowledge of DICOM's benefits and realistic understanding of its limitations enable one to use the Standard effectively as the basis for a long term implementation strategy for image management and communications systems. C1 DUKE UNIV,MED CTR,CTR OUTCOMES MEASUREMENT,DURHAM,NC 27706. NIH,NATL LIB MED,LISTER HILL NATL CTR BIOMED COMMUN,COGNIT SCI BRANCH,BETHESDA,MD. HOSP UNIV PENN,DEPT RADIOL,PHILADELPHIA,PA 19104. RP Bidgood, WD (reprint author), DUKE UNIV,MED CTR,DEPT COMMUNITY & FAMILY MED,DIV MED INFORMAT,BOX 3321,DURHAM,NC 27710, USA. NR 21 TC 125 Z9 127 U1 3 U2 16 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAY-JUN PY 1997 VL 4 IS 3 BP 199 EP 212 PG 14 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA WX671 UT WOS:A1997WX67100003 PM 9147339 ER PT J AU Sloand, JA Sloand, EM AF Sloand, JA Sloand, EM TI Studies on platelet membrane glycoproteins and platelet function during hemodialysis SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID RENAL-FAILURE; VONWILLEBRAND-FACTOR; ACTIVATED PLATELETS; CARDIOPULMONARY BYPASS; ADENOSINE-DIPHOSPHATE; MONOCLONAL-ANTIBODY; DIALYSIS PATIENTS; ANTITHROMBIN-III; IB; UREMIA AB Hemodialysis only partially corrects the defects in platelet function associated with uremia. Platelet contact with the artificial surfaces of the dialysis filter during hemodialysis can itself cause platelet activation, degranulation, and loss of platelet membrane glycoproteins. Although the transient platelet dysfunction that occurs after platelet contact with foreign surfaces during cardiopulmonary bypass has been well characterized, there has been no such investigation of hemodialysis. In this study of hemodialysis patients, bleeding times (BT) and the response of their platelets to thrombin, ristocetin, and collagen were measured before, immediately after, and in some patients, the day after hemodialysis. In addition, membrane glycoproteins in platelets obtained at these time intervals were studied using fluorescein isothiocyanate (FITC) conjugated monoclonal antibodies (mAb) CD42b (anti-GPIb), CD41a (anti-GPIIb/IIIb), and CD62 (anti-P-selectin), with flow cytometry. BT was significantly prolonged, and response to thrombin and ristocetin was significantly decreased immediately after hemodialysis (P < 0.01). Binding of CD42b mAb to the platelet membrane was decreased in platelets obtained immediately after hemodialysis. Most patients had shortened BT and demonstrated increased response of their platelets to thrombin and increased CD42b binding to their platelets the day after hemodialysis. These findings suggest that in uremic patients, hemodialysis is associated with transient platelet dysfunction and decreased membrane expression of GPIb. C1 NHLBI,BETHESDA,MD 20892. RP Sloand, JA (reprint author), UNIV ROCHESTER,SCH MED,HIGHLAND HOSP,NEPHROL UNIT,ROCHESTER,NY 14620, USA. NR 51 TC 37 Z9 38 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAY PY 1997 VL 8 IS 5 BP 799 EP 803 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA XB644 UT WOS:A1997XB64400012 PM 9176850 ER PT J AU Hansard, LJ HealyGardner, BE Drapkin, AT Bentley, RC McLachlan, JA Walmer, DK AF Hansard, LJ HealyGardner, BE Drapkin, AT Bentley, RC McLachlan, JA Walmer, DK TI Human endometrial transforming growth factor-alpha: A transmembrane, surface epithelial protein that transiently disappears during the midsecretory phase of the menstrual cycle SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Article DE TGF-alpha; endometrium; luminal epithelium; human ID MOUSE UTERUS; TGF-ALPHA; PERIIMPLANTATION PERIOD; FACTOR RECEPTOR; INSULIN-LIKE; EXPRESSION; CELL; PROGESTERONE; PRECURSOR; DIETHYLSTILBESTROL AB OBJECTIVE: To characterize the forms of transforming growth factor-alpha (TGF-alpha) in normal human endometrium, to evaluate the regional and temporal changes in TGF-alpha expression, and to correlate the pattern of TGF-alpha expression with physiologic events in the endometrium. METHODS: Immunohistochemistry and Western blot analyses were performed using two TGF-alpha antisera, one raised against the active extracellular N-terminus and the other recognizing the intracellular carboxy terminus of the protein. Immunohistochemistry was performed on hysterectomy specimens from premenopausal women with normal menstrual cycles. Soluble and membrane-bound endometrial proteins were isolated from fresh tissue for Western blot analysis. RESULTS: Antibodies recognizing the intracellular and extracellular domains of TGF-alpha exhibited identical immunohistochemical staining patterns. Transforming growth factor-alpha localized primarily to endometrial epithelial cells, and the most intense staining was in the luminal surface epithelium. In the surface epithelium, TGF-alpha staining was intense in the proliferative phase, decreased during the early secretory phase, was at its nadir in the midsecretory phase, and rebounded in the late secretory phase. Western blot analysis demonstrated two transmembrane forms. The 28-kD protein contained both intracellular and extracellular antigens, and the 18-kD protein contained only the intracellular antigen. CONCLUSION: Western blot data were consistent with the hypothesis that the extracellular segment of TGF-alpha is cleaved from the transmembrane precursor in vivo, as has been demonstrated in other tissues. Immunohistochemistry demonstrated that the TGF-alpha antigens are concentrated in the luminal surface epithelium and decline and disappear in the early to midsecretory phase. These findings suggest that the most active period of membrane-bound TGF-alpha cleavage corresponds with the interval during which preimplantation embryos are in the uterine cavity. Copyright (C) 1997 by the Society for Gynecologic Investigation. C1 DUKE UNIV,MED CTR,DEPT OBSTET & GYNECOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT PATHOL,DURHAM,NC 27710. TULANE UNIV,DEPT PHARMACOL,TULANE XAVIER CTR BIOENVIRONM RES,NEW ORLEANS,LA 70118. NATL INST ENVIRONM HLTH SCI,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC. NR 34 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD MAY-JUN PY 1997 VL 4 IS 3 BP 160 EP 166 DI 10.1016/S1071-5576(97)00016-6 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XN725 UT WOS:A1997XN72500009 PM 9258881 ER PT J AU Meyer, DJ Thompson, MB Senior, DF AF Meyer, DJ Thompson, MB Senior, DF TI Use of ursodeoxycholic acids in a dog with chronic hepatitis: Effects on serum hepatic tests and endogenous bile acid composition SO JOURNAL OF VETERINARY INTERNAL MEDICINE LA English DT Article ID PRIMARY BILIARY-CIRRHOSIS; CHENODEOXYCHOLIC ACID; CELL-LINE; RAT-LIVER; MITOCHONDRIA; HEPATOCYTES; CHOLESTASIS; ABSORPTION; TOXICITY; HUMANS AB A dog with severe cholestasis secondary to chronic hepatitis was treated with ursodeoxycholic acid (UDCA) PO, After 2 weeks of daily treatment, the dog was more active and had an improved appetite, Monthly serum biochemical determinations and analysis of individual bile acid profiles documented improvement in hepatobiliary tests and a marked reduction in the concentrations of potentially hepatotoxic endogenous bile acids. These effects were maintained for approximately 6 months, The findings in this dog are similar to those reported for human patients treated with UDCA and provide preliminary evidence in support of its continued evaluation in the treatment of cholestatic liver disease in the dog. Copyright (C) 1997 by the American College of Veterinary Internal Medicine. C1 UNIV FLORIDA,COLL MED,DEPT PHYSIOL SCI,GAINESVILLE,FL. NIEHS,RES TRIANGLE PK,NC 27709. LOUISIANA STATE UNIV,SCH VET MED,DEPT VET CLIN SCI,BATON ROUGE,LA 70803. NR 25 TC 15 Z9 15 U1 0 U2 8 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0891-6640 J9 J VET INTERN MED JI J. Vet. Intern. Med. PD MAY-JUN PY 1997 VL 11 IS 3 BP 195 EP 197 PG 3 WC Veterinary Sciences SC Veterinary Sciences GA XC705 UT WOS:A1997XC70500009 PM 9183773 ER PT J AU Engelman, A Liu, Y Chen, HM Farzan, M Dyda, F AF Engelman, A Liu, Y Chen, HM Farzan, M Dyda, F TI Structure-based mutagenesis of the catalytic domain of human immunodeficiency virus type 1 integrase SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 INTEGRASE; VIRAL REPLICATION; ESCHERICHIA-COLI; GENETIC-ANALYSIS; PROTEIN INVITRO; I INTEGRASE; DNA-BINDING; IDENTIFICATION; RESIDUES; MUTATIONS AB Two different crystal structures of the human immunodeficiency virus type 1 (HIV-1) integrase (IN) catalytic domain were analyzed for interactions at the enzyme active site, Gln-62 and Glu-92 interact with active-site residue Asp-64, and Lys-136 interacts with active-site residue Asp-116 across a dimer interface, Conservative and nonconservative substitutions were introduced at these positions to probe the roles of these interactions in HIV-1 integration, Purified mutant proteins were assayed for in vitro 3' processing, DNA strand transfer, and disintegration activities, and HIV-1 mutants were assayed for virion protein composition, reverse transcription, and infectivities in human cell lines. Each of the mutant IN proteins displayed wild-type disintegration activity, indicating that none of the interactions is essential for catalysis, Mutants carrying Gin or Ala for Glu-92 displayed wild-type activities, but substituting Lys for Glu-92 reduced in vitro 3' processing and DNA strand transfer activities 5- to 10-fold and yielded a replication-defective IN active-site mutant viral phenotype. Substituting Glu for Gln-62 reduced in vitro 3' processing and DNA strand transfer activities 5- to 10-fold without grossly affecting viral replication kinetics, suggesting that HIV-1 can replicate in T-cell lines with less than the wild-type level of IN activity, The relationship between IN solubility and HIV-I replication was also investigated, We previously showed that substituting Lys for Phe-185 dramatically increased the solubility of recombinant IN but caused an HIV-1 particle assembly defect. Mutants carrying His at this position displayed increased solubility and wild-type replication kinetics, showing that increased IN solubility per se is not detrimental to virus growth. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NIDDKD,MOL BIOL LAB,BETHESDA,MD 20892. RP Engelman, A (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI39394] NR 50 TC 51 Z9 51 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1997 VL 71 IS 5 BP 3507 EP 3514 PG 8 WC Virology SC Virology GA WT189 UT WOS:A1997WT18900018 PM 9094622 ER PT J AU Digilio, L Giri, A Cho, N Slattery, J Markham, P Franchini, G AF Digilio, L Giri, A Cho, N Slattery, J Markham, P Franchini, G TI The simian T-lymphotropic/leukemia virus from Pan paniscus belongs to the type 2 family and infects Asian macaques SO JOURNAL OF VIROLOGY LA English DT Article ID COMPLETE NUCLEOTIDE-SEQUENCE; LEUKEMIA-LYMPHOMA VIRUS; TROPICAL SPASTIC PARAPARESIS; HTLV-II INFECTION; CELL LEUKEMIA; PHYLOGENETIC RELATIONSHIP; CENTRAL-AFRICA; DRUG-ABUSERS; ANTIBODIES; RETROVIRUS AB The proviral DNA of the simian T-leukemia/lymphotropic virus (STLV) isolate, originally obtained from a captive colony of pygmy chimpanzees (Pan paniscus) (STLV(pan-p)), was cloned from the DNA of the chronically infected human T-cell line L93-79B. The entire proviral DNA sequence was obtained and compared with sequences of the known genotypes of STLV and human T-leukemia/lymphotropic virus types 1 and 2 (HTLV-1 and -2). Phylogenetic analysis indicates that STLV-2(pan-p) is an early divergence within the type 2 lineage and should he referred to as STLV-2(pan-p) Since STLV-2(pan-p) has been found in African nonhuman primates, we investigated its infectiousness and pathogenicity in Asian monkeys. Pigtailed macaques were inoculated with human cells harboring STLV(pan-p), and infection was assessed by virus isolation, PCR analysis of peripheral blood mononuclear cells, and seroconversion against viral antigens in HTLV-1/HTLV-2 and Western blot assay. Pigtailed macaques became persistently infected by STLV-2(pan-p), and the virus could be transferred by blood transfusion from an infected pigtailed macaque to a rhesus macaque. In addition, like HTLV-1 and HTLV-2, STLV-2(pan-p) was infectious in rabbits. In summary, STLV-2(pan-p) is a novel retrovirus distantly related to HTLV-2 and displays a host range similar to that demonstrated for other HTLV and STLV strains. C1 NCI,BASIC RES LAB,NIH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,GENOM DIVERS LAB,FREDERICK,MD 21701. ADV BIOSCI LABS INC,KENSINGTON,MD 20895. NR 60 TC 27 Z9 27 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1997 VL 71 IS 5 BP 3684 EP 3692 PG 9 WC Virology SC Virology GA WT189 UT WOS:A1997WT18900038 PM 9094642 ER PT J AU Doherty, TM Giese, N Morse, HC Coffman, RL AF Doherty, TM Giese, N Morse, HC Coffman, RL TI Modulation of murine AIDS-related pathology by concurrent antibody treatment and coinfection with Leishmania major SO JOURNAL OF VIROLOGY LA English DT Article ID RETROVIRUS-INDUCED IMMUNODEFICIENCY; CD4+ T-CELLS; ANTIGEN-PRESENTING CELL; SYNDROME MAIDS; DEFECTIVE VIRUS; DOWN-REGULATION; LEUKEMIA-VIRUS; PROTECTS MICE; C57BL/6 MICE; MOUSE AB Infection of C57BL/6 mice with a mixture of murine leukemia viruses (MuLVs) designated LP-BM5 MuLV leads to a disease characterized by progressive immunodeficiency and lymphoproliferation, known as murine AIDS (MAIDS), The development of MAIDS is associated with increased B-cell lymphoblast proliferation, but there is reason to believe that T-cell function and, particularly, T-cell-derived cytokines may also play a role. We have previously shown that concurrent infection with Leishmania major (which induces a strongly polarized Th1 response in C57BL/6 mice) and LP-BM5 MuLV modulates the disease induced by both infections, Here we show by treatment of mice with anticytokine antibodies that this modulation is largely exerted through the balance of Th1 and Th2 cytokines. Infected mice treated with antibodies to interleukin-4 and interleukin-10 exhibited a delayed development of MAIDS-related pathology and maintained T-cell responsiveness longer than mice treated with control antibody. Gamma interferon induced by coinfection with L. major synergized with anti-IL-4 treatment to inhibit the development of MAIDS pathology, Conversely, treatment with anti-gamma interferon led to a significant increase in splenomegaly and lymphadenopathy and slightly exacerbated loss of T-cell function, These data suggest that the production of Th2-associated cytokines may promote MAIDS pathology, while Th1-associated cytokines may help control the disease. C1 NIAID,IMMUNOPATHOL LAB,NIH,BETHESDA,MD 20892. DNAX RES INST MOL & CELLULAR BIOL INC,DEPT IMMUNOL,PALO ALTO,CA 94304. RP Doherty, TM (reprint author), NIAID,PARASIT DIS LAB,NIH,BLDG 4,BETHESDA,MD 20892, USA. OI Morse, Herbert/0000-0002-9331-3705 FU NIAID NIH HHS [N0I-AI-72622] NR 46 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1997 VL 71 IS 5 BP 3702 EP 3709 PG 8 WC Virology SC Virology GA WT189 UT WOS:A1997WT18900040 PM 9094644 ER PT J AU Hickman, ES Bates, S Vousden, KH AF Hickman, ES Bates, S Vousden, KH TI Perturbation of the p53 response by human papillomavirus type 16 E7 SO JOURNAL OF VIROLOGY LA English DT Article ID RETINOBLASTOMA SUSCEPTIBILITY GENE; P53-DEPENDENT G(1) ARREST; CELL-CYCLE PROGRESSION; WILD-TYPE P53; DNA-DAMAGE; HUMAN FIBROBLASTS; CERVICAL-CARCINOMA; GROWTH ARREST; TRANSCRIPTIONAL ACTIVATION; ALTERED EXPRESSION AB The p53 tumor suppressor protein can induce both cell cycle arrest and apoptosis in DNA-damaged cells. In human carcinoma cell lines expressing wild-type p53, expression of E7 allowed the continuation of full cell cycle progression following DNA damage, indicating that E7 can overcome both G(1) and G(2) blocks imposed by p53. E7 does not interfere with the initial steps of the p53 response, however, and E7 expressing cells showed enhanced expression of p21(waf1/cip1) and reductions in cyclin E- and A-associated kinase activities following DNA damage. One function of cyclin-dependent kinases is to phosphorylate pRB and activate E2F, thus allowing entry into DNA synthesis. Although E7 may substitute for this activity during cell division by directly targeting pRB, continued cell cycle progression in E7-expressing cells was associated with phosphorylation of pRB, suggesting that E7 permits the retention of some cyclin-dependent kinase activity, One source of this activity may be the E7-associated kinase, which was not inhibited following DNA damage. Despite allowing cell cycle progression, E7 was unable to protect cells from p53-induced apoptosis, and the elevated apoptotic response seen in these cells correlated with the reduction of cyclin A-associated kinase activity, It is possible that inefficient cyclin A-dependent inactivation of E2F at the end of DNA synthesis contributes to the enhanced apoptosis displayed by E7-expressing cells. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 81 TC 42 Z9 42 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1997 VL 71 IS 5 BP 3710 EP 3718 PG 9 WC Virology SC Virology GA WT189 UT WOS:A1997WT18900041 PM 9094645 ER PT J AU Wolffe, EJ Katz, E Weisberg, A Moss, B AF Wolffe, EJ Katz, E Weisberg, A Moss, B TI The A34R glycoprotein gene is required for induction of specialized actin-containing microvilli and efficient cell-to-cell transmission of vaccinia virus SO JOURNAL OF VIROLOGY LA English DT Article ID EXTRACELLULAR VIRUS; ENVELOPE PROTEIN; HEMAGGLUTININ GENE; RELEASE; MEMBRANE; POLYPEPTIDE; DELETION; FUSION; DISSEMINATION; CYTOSKELETON AB The mechanisms allowing vaccinia virus to spread from cell to cell are incompletely understood, The A34R gene of vaccinia virus encodes a glycoprotein that is localized in the outer membranes of extracellular virions, The small-plaque phenotype of an A34R deletion mutant was similar to that of mutants,vith deletions in other envelope genes that fail to produce extracellular vaccinia virions. Transmission electron microscopy, however, revealed that the A34R mutant produced numerous extracellular particles that were labeled with antibodies to other outer-envelope proteins and with protein A-colloidal gold, Fluorescence and scanning electron microscopy indicated that expression of the A34R protein was necessary for detection of vaccinia virus-induced actin tails, which provide motility to the intracellular enveloped form of vaccinia virus, and of virus-tipped specialized microvilli that project from the cell, The ability of vaccinia virus-infected cells to form syncytia after a brief exposure to a pH below 6, known as fusion from within, failed to occur in the absence of expression of the A34R protein; nevertheless, purified A34R(-) virions were capable of mediating low-pH-induced fusion from without. The present study provides genetic and microscopic evidence for the involvement of a specific viral protein in the formation or stability of actin-containing microvilli and for a role of these structures in cell-to-cell spread rather than in formation of extracellular virions. C1 NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT VIROL,IL-91120 JERUSALEM,ISRAEL. NR 44 TC 85 Z9 86 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1997 VL 71 IS 5 BP 3904 EP 3915 PG 12 WC Virology SC Virology GA WT189 UT WOS:A1997WT18900063 PM 9094667 ER PT J AU Caughey, B Raymond, GJ Kocisko, DA Lansbury, PT AF Caughey, B Raymond, GJ Kocisko, DA Lansbury, PT TI Scrapie infectivity correlates with converting activity, protease resistance, and aggregation of scrapie-associated prion protein in guanidine denaturation studies SO JOURNAL OF VIROLOGY LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; CONFORMATIONAL TRANSITIONS; AGENT; FORMS AB Denaturation studies with guanidine HCl (GdnHCl) were performed to test the relationship between scrapie infectivity and properties of scrapie-associated prion protein (PrPSc). Large GdnHCl-induced reductions in infectivity were associated,vith the irreversible elimination of both the proteinase K resistance and apparent self-propagating converting activity of PrPSc. In intermediate GdnHCl concentrations that stimulate converting activity and partially disaggregate PrPSc, both scrapie infectivity and converting activity were associated with residual partially protease-resistant multimers of PrPSc. C1 MIT,DEPT CHEM,CAMBRIDGE,MA 02139. RP Caughey, B (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,NIH,HAMILTON,MT 59840, USA. NR 25 TC 100 Z9 102 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1997 VL 71 IS 5 BP 4107 EP 4110 PG 4 WC Virology SC Virology GA WT189 UT WOS:A1997WT18900087 PM 9094691 ER PT J AU Kuo, H Hengemihle, J Ingram, DK AF Kuo, H Hengemihle, J Ingram, DK TI Nitric oxide synthase in rat brain: Age comparisons quantitated with NADPH-diaphorase histochemistry SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID CHOLINERGIC NEURONS; HUNTINGTONS-DISEASE; ALZHEIMERS-DISEASE; STRIATAL NEURONS; LOCUS COERULEUS; HIPPOCAMPUS; NUCLEUS; NUMBERS; SYSTEM; MARKER AB We examined age-related differences in nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) containing neurons and neuropil in the striatum and hippocampus of male Fischer 344 rats at 6, 12, and 26 mo of age. NADPH-d staining is considered to he a marker for neurons and neuronal processes containing nitric oxide synthase. Rat brains were processed for NADPH-d histochemistry and analysed morphometrically using computerized image analysis. The following NADPH-d histochemical parameters were examined: neuronal density, neuronal size, and neuropil staining optical density of selected regions. In the striatum, significant age-related declines were observed in NADPH-d-positive neuronal density and in neuropil staining, while neuronal size increased between 6 and 12 mo and then declined between 12 and 26 mo. In the hippocampus no significant age-related changes were rioted in NADPH-d-positive neuronal density or size, or in the optical density of the molecular layer of the hippocampal dentate gyrus. Thus, age differences in NADPH-d histochemistry appear to be regionally specific in the Fischer 344 rat. C1 NIA, NIH,GERONTOL RES CTR,MOL PHYSIOL & GENET SECT, NATHAN W SHOCK LABS, BALTIMORE, MD 21224 USA. NR 48 TC 8 Z9 8 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 1997 VL 52 IS 3 BP B146 EP B151 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA WZ219 UT WOS:A1997WZ21900003 PM 9158548 ER PT J AU Pearson, JD Morrell, CH Brant, LJ Landis, PK Fleg, JL AF Pearson, JD Morrell, CH Brant, LJ Landis, PK Fleg, JL TI Age-associated changes in blood pressure in a longitudinal study of healthy men and women SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID EFFECTS MODELS AB Background. Current knowledge of age-associated increases in blood pressure is based primarily on unscreened population studies that may not be representative of healthy men and women. We examined longitudinal patterns of change in blood pressure in healthy male and female volunteers from the Baltimore Longitudinal Study of Aging (BLSA). Methods. Longitudinal mixed-effects regression models are used to estimate the age-associated changes in brood pressure in 1307 men (age 17-97) and 333 women (age 18-93) who have been followed for up to 32 years (mean: 8.4 years for men and 3.4 years for women) and who have been screened for hearth problems or medications that affect blood pressure. Results. On average, systolic pressure is relatively stable in men and women until approximately age 45, increases at 5-8 mm Hg per decade in middle age, then accelerates in men and stabilizes in women. Diastolic pressure increases at 1 mm Hg per decade at all ages in men, whereas in women the rate of change in diastolic pressure increases in middle age and then plateaus and may decline after age 70. Additional findings include: (a) BLSA cross-sectional and longitudinal findings are more similar than has been observed in studies of unscreened samples; (b) there is no evidence of a gender cross-over in this group of healthy men and women; and (c) compared to previous studies of unscreened samples, healthy BLSA men and women show a weaker association between baseline blood pressure and subsequent rate of blood pressure change. Conclusions. These findings suggest that several previously described age-associated patterns of blood pressure change partially reflect the effects of hypertension and its treatment, rather than intrinsic age changes in the blood pressure of healthy individuals. C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 26 TC 58 Z9 60 U1 0 U2 2 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 1997 VL 52 IS 3 BP M177 EP M183 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA WZ219 UT WOS:A1997WZ21900015 PM 9158560 ER PT J AU Roubenoff, R Baumgartner, RN Harris, TB Dallal, GE Hannan, MT Economos, CD Stauber, PM Wilson, PWF Kiel, DP AF Roubenoff, R Baumgartner, RN Harris, TB Dallal, GE Hannan, MT Economos, CD Stauber, PM Wilson, PWF Kiel, DP TI Application of bioelectrical impedance analysis to elderly populations SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID BODY-MASS INDEXES; X-RAY ABSORPTIOMETRY; SOFT-TISSUE; IN-VIVO; AGE; FAT; VALIDATION; POTASSIUM; FEMALES; WOMEN AB Background. Bioelectrical impedance analysis (BIA) can potentially be used to estimate body composition in large populations studied at multiple sites. However, it is not clear whether age-specific BIA equations are necessary for accurate application of BIA to research on elderly subjects. Methods. We compared a published equation designed to predict fat-free mass (FFM) that had been derived in a young healthy population (mean age 27 y; mean BMI 23.9 kg/m(2)), with equations that we developed for the elderly by using data from 455 participants in the Framingham Heart Study (78 y; 27.3 kg/m(2)), using dual-energy x-ray absorptiometry (DXA) as a reference technique. The BIA equations were then compared in an independent sample of 283 participants in the New Mexico Aging Process Study (76 y, 25.5 kg/m(2)), who also underwent BIA and DXA. Results. When the young-population equation was applied to Framingham, it caused an overestimation of FFM in heavier subjects that was eliminated by use of the age-specific equation. However, when the two equations were tested in the New Mexico population, the published equation gave estimates of FFM that were closer to DXA than the Framingham equations did. Conclusions. The accuracy of a BIA equation depends on the body composition of the population and the validation method rather than on age per se. Application of BIA to elderly populations requires uniform validation procedures in the actual study population, rather than reliance on age-specific equations. C1 UNIV NEW MEXICO, SCH MED, CLIN NUTR PROGRAM, ALBUQUERQUE, NM 87131 USA. NIA, GERIATR EPIDEMIOL OFF, BETHESDA, MD 20892 USA. BOSTON UNIV, SCH MED, BOSTON, MA 02215 USA. FRAMINGHAM HEART DIS EPIDEMIOL STUDY, FRAMINGHAM, MA USA. HEBREW REHABIL CTR AGED, RES & TRAINING INST, BOSTON, MA 02131 USA. RP Roubenoff, R (reprint author), TUFTS UNIV, USDA, HUMAN NUTR RES CTR AGING, BODY COMPOSIT LAB, 711 WASHINGTON ST, BOSTON, MA 02111 USA. FU NIA NIH HHS [Y01 AG-20195]; NIAMS NIH HHS [AR-41398]; NIDDK NIH HHS [DK-08443] NR 32 TC 135 Z9 138 U1 1 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 1997 VL 52 IS 3 BP M129 EP M136 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA WZ219 UT WOS:A1997WZ21900008 PM 9158553 ER PT J AU Myers, GC Juster, FT Suzman, RM AF Myers, GC Juster, FT Suzman, RM TI Asset and Health Dynamics Among the Oldest Old (AHEAD): Initial results from the longitudinal study - Introduction SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Editorial Material C1 UNIV MICHIGAN,INST SOCIAL RES,ANN ARBOR,MI. UNIV MICHIGAN,INST SOCIAL RES,ANN ARBOR,MI 48106. NIA,OFF DEMOG,NIH,BETHESDA,MD 20892. RP Myers, GC (reprint author), DUKE UNIV,CTR DEMOG STUDIES,DURHAM,NC 27708, USA. NR 5 TC 31 Z9 31 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD MAY PY 1997 VL 52 SI SI BP R5 EP R8 PG 4 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA XJ377 UT WOS:A1997XJ37700001 PM 9215353 ER PT J AU Bernard, SL Kincade, JE Konrad, TR Arcury, TA Rabiner, DJ Woomert, A DeFriese, GH Ory, MG AF Bernard, SL Kincade, JE Konrad, TR Arcury, TA Rabiner, DJ Woomert, A DeFriese, GH Ory, MG TI Predicting mortality from community surveys of older adults: The importance of self-rated functional ability SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article ID HEALTH-STATUS; FOLLOW-UP; PERCEIVED HEALTH; PHYSICAL HEALTH; ASSESSED HEALTH; ASSESSMENTS; ASSISTANCE; SURVIVAL; COHORT; AGE AB Using data from the 1990 baseline of the National Survey of Self-Care and Aging (NSSCA), and nearly three years of follow-up mortality data, we examined the association between self-rated functional ability, a global measure of perceived ability to function independently, and mortality among a national sample of older adults. The study included 3,485 subjects selected from the Medicare Beneficiary Files according to a stratified random sampling design, with approximately equal numbers of adults by gender in each of three age categories, 65-74, 75-84, and 85 and over. Self-rated functional ability was found to have an independent contribution to the subsequent risk of death among older adults. Using multivariate models that accounted for self-rated health, age, gender, medical conditions, functional status, and assistance from others, poor self-ratings on this single item nearly doubled the risk of death during the follow-up period. These findings suggest the importance, for both researchers and clinicians, of measuring the potential prognostic importance of self-ratings of health and self-ratings of functional ability among older adults. C1 UNIV N CAROLINA,CECIL G SHEPS CTR HLTH SERV RES,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT HLTH POLICY & ADM,CHAPEL HILL,NC 27599. UNIV N CAROLINA,CURRICULUM PUBL HLTH NURSING,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT SOCIAL MED,CHAPEL HILL,NC 27599. UNIV N CAROLINA,CTR URBAN & REG STUDIES,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT EPIDEMIOL,CHAPEL HILL,NC 27599. VET ADM MED CTR,NATL CTR HLTH PROMOT,DURHAM,NC. BATTELLE SURVEY OPERAT,DURHAM,NC. NIA,NIH,BETHESDA,MD 20892. FU PHS HHS [A07929-02] NR 40 TC 63 Z9 64 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD MAY PY 1997 VL 52 IS 3 BP S155 EP S163 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA WZ217 UT WOS:A1997WZ21700012 PM 9158572 ER PT J AU Bottinger, EP Letterio, JJ Roberts, AB AF Bottinger, EP Letterio, JJ Roberts, AB TI Biology of TGF-beta in knockout and transgenic mouse models SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT ISN Forefronts in Nephrology Symposium on Cytokines and Adhesion Molecules in Tissue Injury and Repair CY SEP 12-15, 1996 CL SNOWBIRD, UT SP ISN ID GROWTH-FACTOR-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; BREAST-CANCER; MICROSATELLITE INSTABILITY; AUTOIMMUNE-DISEASE; BINDING-PROTEIN; MICE; FACTOR-BETA-1; RECEPTOR; PLASMA AB This paper reviews the basic biology and biochemistry of the TGF-P isoforms including their unique serine-threonine receptors and signaling intermediates. Dysregulation of TGF-beta expression and/or recepotr/signaling function have been implicated in a wide variety of pathologies. We will discuss mechanisms underlying some of these disease processes as gained from study of transgenic mice in which expression of TGF-beta 1 has either been lost by targeted deletion of its gene, is overexpressed in a tissue-specific manner, or blocked by its latency associated peptide. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NR 69 TC 120 Z9 127 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 1997 VL 51 IS 5 BP 1355 EP 1360 DI 10.1038/ki.1997.185 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA WX906 UT WOS:A1997WX90600005 PM 9150444 ER PT J AU Wahl, SM FrazierJessen, M Jin, WW Kopp, JB Sher, A Cheever, AW AF Wahl, SM FrazierJessen, M Jin, WW Kopp, JB Sher, A Cheever, AW TI Cytokine regulation of schistosome-induced granuloma and fibrosis SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT ISN Forefronts in Nephrology Symposium on Cytokines and Adhesion Molecules in Tissue Injury and Repair CY SEP 12-15, 1996 CL SNOWBIRD, UT SP ISN ID GROWTH-FACTOR-BETA; MANSONI-INFECTED MICE; BRONCHIAL EPITHELIAL-CELLS; MURINE SCHISTOSOMIASIS; TRANSFORMING GROWTH-FACTOR-BETA-1; EGG GRANULOMAS; HEPATIC-FIBROSIS; TH2 CYTOKINES; T-CELLS; IN-VIVO AB Schistosomiasis mansoni, a major cause of hepatic fibrosis in many developing countries, triggers a granulomatous inflammatory reaction in response to its eggs that lodge in the liver. The egg antigens are eliminated slowly, and the persistent granulomatous response leads to prolonged matrix synthesis and hepatic fibrosis. In mice, soluble egg antigens (SEA) induce interleukin 4 synthesis, promoting a dominant T helper type 2 lymphocyte accumulation with the release of additional cytokines (IL-5, IL-10), which not only suppress Th1 lymphocyte subset cytokines, but mediate the characteristic pathophysiology. Manipulation of the cytokine profile with antagonists or exogenous cytokine delivery alters the course of the hepatic inflammation and fibrosis. In the evolution of the granulomatous response to the S. mansoni eggs, transforming growth factor beta (TGF-beta) is also produced that may modulate inflammation and regulate fibrogenesis. In TGF-beta 1-gene targeted mutant mice that over-express TGF-beta 1 (TGF-beta 1 transgenics) or in which TGF-beta 1 has been inactivated (TGF-beta 1 -/-; null mutation) or partially inactivated (TGF-beta 1 +/-; null mutation heterozygotes), the altered production of TGF-beta 1 impacts on S. mansoni granuloma and hepatic fibrosis. In addition to the Th1/Th2 cytokine balance, modulation of TGF-beta 1 may change the outcome of chronic inflammatory fibrotic disease. C1 NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. BIOMED RES INST,ROCKVILLE,MD 20852. RP Wahl, SM (reprint author), NIDR,NIH,NIDDK,METAB DIS BRANCH,KIDNEY DIS SECT,LAB IMMUNOL,30 CONVENT DR,MSC 4352,BLDG 30,BETHESDA,MD 20892, USA. OI Kopp, Jeffrey/0000-0001-9052-186X NR 62 TC 36 Z9 42 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 1997 VL 51 IS 5 BP 1370 EP 1375 DI 10.1038/ki.1997.187 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA WX906 UT WOS:A1997WX90600007 PM 9150446 ER PT J AU Goligorsky, MS Noiri, E Kessler, H Romanov, V AF Goligorsky, MS Noiri, E Kessler, H Romanov, V TI Therapeutic potential of RGD peptides in acute renal injury SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT ISN Forefronts in Nephrology Symposium on Cytokines and Adhesion Molecules in Tissue Injury and Repair CY SEP 12-15, 1996 CL SNOWBIRD, UT SP ISN ID INTERCELLULAR-ADHESION MOLECULE-1; EXTRACELLULAR-MATRIX; CELL-ADHESION; INTEGRINS; FIBRONECTIN; RECOGNITION; RECEPTORS; COLLAGEN; ANTIBODY; KIDNEY C1 TECH UNIV MUNICH,D-8000 MUNICH,GERMANY. NATL CANC INST,FREDERICK,MD. RP Goligorsky, MS (reprint author), SUNY STONY BROOK,DIV NEPHROL & HYPERTENS,STONY BROOK,NY 11794, USA. RI Kessler, Horst/C-1178-2010 FU NIDDK NIH HHS [DK 41573, DK 45695] NR 48 TC 27 Z9 29 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 1997 VL 51 IS 5 BP 1487 EP 1492 DI 10.1038/ki.1997.204 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA WX906 UT WOS:A1997WX90600023 PM 9150463 ER PT J AU Bodi, I Kimmel, PL Abraham, AA Svetkey, LP Klotman, PE Kopp, JB AF Bodi, I Kimmel, PL Abraham, AA Svetkey, LP Klotman, PE Kopp, JB TI Renal TGF-beta in HIV-associated kidney diseases SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT ISN Forefronts in Nephrology Symposium on Cytokines and Adhesion Molecules in Tissue Injury and Repair CY SEP 12-15, 1996 CL SNOWBIRD, UT SP ISN ID GROWTH-FACTOR-BETA; IMMUNODEFICIENCY-VIRUS INFECTION; TGF-BETA-1 MESSENGER-RNA; MONOCLONAL-ANTIBODY; EXTRACELLULAR-MATRIX; EXPRESSION; FACTOR-BETA-1; NEPHROPATHY; EOSINOPHILS; GLOMERULONEPHRITIS AB Human immunodeficiency virus (HIV)-1 infection may be complicated by progressive renal glomerular disease, including focal segmental glomerulosclerosis (FSGS) and proliferative glomerulonephritis. We examined renal tissue from 71 patients, including biopsies and autopsies from patients in the presence and absence of HIV-1 infection. We assessed the extent of TGF-P, interstitial fibrosis, and interstitial CD45-positive cellular infiltrate using immunohistochemistry. Extracellular TGF-beta 1/beta 3 was largely confined to the renal interstitium, with the highest scores in HIV-seropositive renal disease and crescentic nephritis. Among all biopsies, the TGF-beta 1/beta 3 score correlated with the fibrosis score (r = 0.79, P < 0.0001) and with the CD45 score (r = 0.60, P < 0.0001). Biopsies from HIV-infected patients, taken together, showed marginally more TGF-beta 1/beta 3 compared to biopsies from HIV-uninfected patients (P = 0.05); similarly, HIV-associated FSGS showed marginally more TGF-beta 1/beta 3 compared to FSGS biopsies obtained from HIV-uninfected patients (P = 0.05). Intracellular TGF-beta 1 and TGF-beta 3 were both expressed by renal tubular epithelial cells and in extraglomerular crescents, whereas TGF-beta 3 was also present within interstitial mononuclear cells and eosinophils, and, exclusively in HIV-infected patients, within glomerular cells. In conclusion, TGF-P expression was increased in several progressive glomerular diseases, and was particularly but not uniquely elevated in HIV-associated renal diseases. C1 NIDDKD,METAB DIS BRANCH,NIH,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,MED CTR,DEPT MED,WASHINGTON,DC 20037. GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20037. DUKE UNIV,MED CTR,DEPT MED,CHAPEL HILL,NC. MT SINAI SCH MED,DEPT MED,NEW YORK,NY. NR 31 TC 48 Z9 49 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 1997 VL 51 IS 5 BP 1568 EP 1577 DI 10.1038/ki.1997.215 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA WX906 UT WOS:A1997WX90600034 PM 9150474 ER PT J AU Matsukawa, A Yoshimura, T Miyamoto, K Ohkawara, S Yoshinaga, M AF Matsukawa, A Yoshimura, T Miyamoto, K Ohkawara, S Yoshinaga, M TI Analysis of the inflammatory cytokine network among TNF alpha, IL-1 beta, IL-1 receptor antagonist, and IL-8 in LPS-induced rabbit arthritis SO LABORATORY INVESTIGATION LA English DT Article ID TUMOR-NECROSIS-FACTOR; NEUTROPHIL CHEMOTACTIC FACTOR; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; GENE-EXPRESSION; INTERLEUKIN-1 IL-1; LIPOPOLYSACCHARIDE; PURIFICATION; RELEASE; CELLS; ANTIBODIES AB We investigated the cytokine network in rabbit lipopolysaccharide (LPS)-induced arthritis, using inhibitors against homologous TNF alpha, IL-1 beta, and IL-8. Rabbits were intraarticularly injected with LPS (10 ng) and cytokine inhibitors (10 mu g each), and the concentrations of each cytokine in the synovial fluids were measured. Maximum levels of TNF alpha and IL-8 were detected at 2 hours after LPS-injection, whereas IL-1 beta and IL-1 receptor antagonist (IL-1Ra) were detected at 6 and 9 hours, respectively. By immunohistochemistry, synovial lining cells were positive for TNF alpha and IL-8, and infiltrating leukocytes were positive for IL-1 beta and IL-1Ra. The effects of cytokine inhibitors on the release of each cytokine were then investigated. The maximum levels of TNF alpha and IL-8 were not affected by blocking the activities of other cytokines. In contrast, the peak concentration of IL-1 beta was reduced by anti-TNF alpha monoclonal Ab (mAb), IL-1Ra or anti-IL-8 IgG. Peak concentrations of IL-l Ra were reduced by anti-TNF alpha mAb or anti-IL-8 IgG. Anti-TNF alpha mAb, IL-1Ra, and anti-IL-8 IgG reduced the recruitment of leukocytes into the joint cavity, and the effect of anti-IL-8 IgG was less than that of anti-TNF alpha mAb plus IL-1Ra. The initial phase of the leukocyte influx was not inhibited. These results provide new evidence that IL-8 as well as TNF alpha are the most proximal cytokines and induce subsequent production of IL-1 beta and IL-1Ra. The data also raise the possibility that factor(s) other than IL-8 may be involved in the leukocyte influx in LPS-induced arthritis. C1 NCI,FREDERICK CANC RES & DEV CTR,IMMUNOL LAB,IMMUNOPATHOL SECT,FREDERICK,MD. RP Matsukawa, A (reprint author), KUMAMOTO UNIV,SCH MED,DEPT PATHOL,2-2-1 HONJO,KUMAMOTO 860,JAPAN. NR 41 TC 72 Z9 74 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAY PY 1997 VL 76 IS 5 BP 629 EP 638 PG 10 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA XA306 UT WOS:A1997XA30600004 PM 9166282 ER PT J AU Friedrich, RW Veit, M Eisel, D Friedich, U Pass, M Kozak, CA AF Friedrich, RW Veit, M Eisel, D Friedich, U Pass, M Kozak, CA TI Fre2, a proviral integration site of Friend murine leukemia virus that is closely linked to Fv2 SO LEUKEMIA LA English DT Review DE Friend murine leukemia virus; Fre2; Fv2; proviral integration site; erythroleukemia ID FOCUS-FORMING VIRUS; CELL-LINE; ERYTHROLEUKEMIA INDUCTION; FLI-1; IDENTIFICATION; CHROMOSOME-3; LYMPHOMAS; DOMAIN; REGION; FV-2 AB Friend murine leukemia virus (F-MuLV) induces leukemia by integration into the cellular genome, thereby changing the structure or expression of cellular oncogenes. In this report we describe a new F-MuLV integration site Fre2 isolated from splenic DNA of an erythroleukemic animal. This site was found to be rearranged in six out of 64 tumors tested; however, in five out of these six cases no F-MuLV proviruses could be detected in the vicinity of the rearrangement sites. The rearrangements represented closely clustered chromosomal breakpoints, presumably chromosomal translocations. Exons transcribed into differentially spliced mRNAs of 1.9 and 3.7 kb have been found near the breakpoint. Fre2 is closely linked to Fv2, a locus on mouse chromosome 9 involved in erythropoiesis. Sequences homologous to Fre2 could not be found in the gene databases. C1 NIAID,MOL MICROBIOL LAB,NIH,BETHESDA,MD 20892. RP Friedrich, RW (reprint author), UNIV GIESSEN,INST MED VIROL,FRANKFURTER STR 107,D-35392 GIESSEN,GERMANY. NR 31 TC 1 Z9 1 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 1997 VL 11 IS 5 BP 619 EP 623 DI 10.1038/sj.leu.2400636 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA XC413 UT WOS:A1997XC41300001 PM 9180281 ER PT J AU Shaw, GL Weiffenbach, B Falk, RT Frame, JN Issaq, HJ Moir, DT Caporaso, N AF Shaw, GL Weiffenbach, B Falk, RT Frame, JN Issaq, HJ Moir, DT Caporaso, N TI Frequency of the variant allele CYP2D6(C) among North American Caucasian lung cancer patients and controls SO LUNG CANCER LA English DT Article DE debrisoquine; lung cancer; genetic susceptibility ID POOR METABOLIZERS; SPARTEINE POLYMORPHISM; DRUG-METABOLISM; POINT MUTATIONS; DEBRISOQUINE; GENE; SUSCEPTIBILITY; IDENTIFICATION; PHENOTYPE; DELETION AB Previous reports of the association between the debrisoquine polymorphism and lung cancer risk are conflicting. Following the report of an association between lung cancer risk and the variant allele CYP2D6(C), we examined the presence of this allele in 98 incident Caucasian lung cancer patients and 110 age, race, and sex matched hospital controls from a case-control study conducted at the National Naval Medical Center in Bethesda, MD. Debrisoquine metabolic phenotype was determined by debrisoquine administration and analysis of debrisoquine and 4-hydroxydebrisoquine in the subsequent 8 h urine collected. Genomic DNA was genotyped bs;a specific polymerase chain reaction amplification and subsequent restriction enzyme digestion, and Southern analysis. Twenty subjects were heterozygous for the CYP2D6(C) allele but none were homozygous for this allele. There was no significant difference in frequency of CYP2D6(C) between lung cancer patients and controls (5.61% and 4.09%. respectively), and there was no significant heterogeneity among cases by histologic type of lung cancer (P = 0.08). However, 7 of 11 cases (64%) with the CYP2D6(C) allele had small cell lung cancer. and none had squamous cell carcinoma. Carrying the CYP2D6(C) allele did nut impair debrisoquine metabolism to the same degree as the known inactivating mutations, CYP2D6(A) and CYP2D6(B), or deletion of CYP2D6. Thus, the CYP2D6(C) allele does not encode a completely inactivating mutation, and the suggestion of a role for this variant allele in the risk for specific histologic types of lung cancer justifies further investigation. (C) 1997 Elsevier Science Ireland Ltd. C1 GENOME THERAPEUT CORP, DEPT HUMAN GENET & MOL BIOL, WALTHAM, MA 02154 USA. NCI, DIV CANC EPIDEMIOL & GENET, NIH, BETHESDA, MD 20892 USA. NATL NAVAL MED CTR, DEPT INTERNAL MED, DIV MED ONCOL, BETHESDA, MD 20889 USA. NCI, FREDERICK CANC RES & DEV CTR, SAIC FREDERICK, FREDERICK, MD 21701 USA. RP Shaw, GL (reprint author), UNIV S FLORIDA, H LEE MOFFITT CANC CTR & RES INST, 12902 MAGNOLIA DR, TAMPA, FL 33612 USA. FU NCI NIH HHS [N01-CP0-5684, N01-CP1-5672] NR 16 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD MAY PY 1997 VL 17 IS 1 BP 61 EP 68 DI 10.1016/S0169-5002(97)00649-1 PG 8 WC Oncology; Respiratory System SC Oncology; Respiratory System GA XE169 UT WOS:A1997XE16900002 PM 9194027 ER PT J AU Hirsch, FR Brambilla, E Gray, N Gritz, E Kelloff, GJ Linnoila, RI Pastorino, U Mulshine, JL AF Hirsch, FR Brambilla, E Gray, N Gritz, E Kelloff, GJ Linnoila, RI Pastorino, U Mulshine, JL TI Prevention and early detection of lung cancer clinical aspects SO LUNG CANCER LA English DT Editorial Material ID TOBACCO C1 CTR HOSP,SERV PATHOL CELLULAIRE,GRENOBLE,FRANCE. EUROPEAN INST ONCOL,DIV EPIDEMIOL & BIOSTAT,MILAN,ITALY. UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX. NCI,CHEMOPREVENT BRANCH,DIV PREVENT & CONTROL,NIH,ROCKVILLE,MD. NCI,CELL & CANC BIOL DEPT,MED BRANCH,DIV CLIN SCI,NIH,ROCKVILLE,MD. ROYAL BROMPTON HOSP,DEPT THORAC SURG,LONDON SW3 6LY,ENGLAND. NCI,CELL & CANC BIOL DEPT,MED BRANCH,DIV CLIN SCI,NIH,ROCKVILLE,MD. RP Hirsch, FR (reprint author), RIGSHOSP,DEPT ONCOL,FINSEN CTR,9 BLEGDAMSVEJ,DK-2100 COPENHAGEN,DENMARK. RI Brambilla, Elisabeth/L-8796-2013; Pastorino, Ugo/C-2712-2017 OI Pastorino, Ugo/0000-0001-9974-7902 NR 26 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD MAY PY 1997 VL 17 IS 1 BP 163 EP 174 DI 10.1016/S0169-5002(97)00033-0 PG 12 WC Oncology; Respiratory System SC Oncology; Respiratory System GA XE169 UT WOS:A1997XE16900010 PM 9194035 ER PT J AU Koch, A Juan, TSC Jenkins, NA Gilbert, DJ Copeland, NG McNiece, IK Fletcher, FA AF Koch, A Juan, TSC Jenkins, NA Gilbert, DJ Copeland, NG McNiece, IK Fletcher, FA TI cDNA cloning and chromosomal mapping of mouse fast skeletal muscle troponin T SO MAMMALIAN GENOME LA English DT Article ID SINGLE GENE; ISOFORMS; ASSIGNMENT; EXON C1 AMGEN INC,DEPT DEV HEMATOL,THOUSAND OAKS,CA 91320. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. NR 13 TC 4 Z9 5 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD MAY PY 1997 VL 8 IS 5 BP 346 EP 348 DI 10.1007/s003359900437 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA WU065 UT WOS:A1997WU06500010 PM 9107680 ER PT J AU Taylor, C Wadey, R ODonnell, H Roberts, C Mattei, MG Kimber, WL WynshawBoris, A Scambler, PJ AF Taylor, C Wadey, R ODonnell, H Roberts, C Mattei, MG Kimber, WL WynshawBoris, A Scambler, PJ TI Cloning and mapping of murine Dgcr2 and its homology to the Sez-12 seizure-related protein SO MAMMALIAN GENOME LA English DT Article ID BALANCED TRANSLOCATION BREAKPOINT; SYNDROME CRITICAL REGION; DIGEORGE-SYNDROME; GENE; 22Q11; VICINITY; MOUSE C1 INST CHILD HLTH,MOL MED UNIT,LONDON WC1N 1EH,ENGLAND. FAC MED MARSEILLE,INSERM,U406,F-13385 MARSEILLE,FRANCE. NIH,LAB GEN DIS RES,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RI Scambler, Peter/C-4998-2008 OI Scambler, Peter/0000-0002-1487-4628 NR 18 TC 17 Z9 18 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD MAY PY 1997 VL 8 IS 5 BP 371 EP 375 DI 10.1007/s003359900445 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA WU065 UT WOS:A1997WU06500018 PM 9107688 ER EF