FN Thomson Reuters Web of Science™ VR 1.0 PT J AU KRISHNA, CM UPPULURI, S RIESZ, P ZIGLER, JS BALASUBRAMANIAN, D AF KRISHNA, CM UPPULURI, S RIESZ, P ZIGLER, JS BALASUBRAMANIAN, D TI A STUDY OF THE PHOTODYNAMIC EFFICIENCIES OF SOME EYE LENS CONSTITUENTS SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID ALPHA-CRYSTALLIN; OXYGEN; SENSITIZER; OXIDATION; PROTEINS AB We have studied the photochemical quantum yields of singlet oxygen production (using the RNO bleaching method) and superoxide production (using the EPR-spin trapping method and the SOD-inhibitable ferricytochrome c reduction spectral assay) of kynurenine (Ky), N-formylkynurenine (NFK), 3-hydroxykynurenine (3HK), kynurenic acid (KUA), and the flavins, riboflavin (RF) and flavin mononucleotide (FMN). Such a study of the photodynamic efficiencies is important since these compounds appear endogenously in the eye. The singlet oxygen quantum yields of the flavins and KUA are high, while Ky and 3HK generate no detectable amounts of singlet oxygen. The superoxide quantum yields of the sensitizers are low compared to their singlet oxygen, and Ky and 3HK produce no detectable amounts of superoxide. The production of the superoxide radical is enhanced in the presence of electron donor molecules such as EDTA and NADH. These results suggest that the production of oxyradicals in the lens may be modulated by the presence of endogenous electron donor molecules such as the coenzymes NADH and NADPH, which are present in significant amounts in some lenses. They also suggest that Ky and 3HK, which are known to be present in aged lenses, might play a protective rather than a deleterious role in the eye. C1 NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NEI,MECHANISMS OCULAR DIS LAB,BETHESDA,MD 20892. CTR CELLULAR & MOLEC BIOL,HYDERABAD 500007,ANDHRA PRADESH,INDIA. NR 36 TC 161 Z9 163 U1 2 U2 11 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUL PY 1991 VL 54 IS 1 BP 51 EP 58 DI 10.1111/j.1751-1097.1991.tb01984.x PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GB386 UT WOS:A1991GB38600008 PM 1658825 ER PT J AU MILLER, M PARK, MK HANOVER, JA AF MILLER, M PARK, MK HANOVER, JA TI NUCLEAR-PORE COMPLEX - STRUCTURE, FUNCTION, AND REGULATION SO PHYSIOLOGICAL REVIEWS LA English DT Review ID EPIDERMAL GROWTH-FACTOR; LARGE-T-ANTIGEN; NF-KAPPA-B; RAT-LIVER NUCLEI; CELL-FREE SYSTEM; SV40 LARGE-T; INTERMEDIATE FILAMENT PROTEINS; MESSENGER-RNA TRANSPORT; AMINO-ACID-SEQUENCE; HEAT-SHOCK PROTEIN RP MILLER, M (reprint author), NIDDKD, BIOCHEM & METAB LAB, BETHESDA, MD 20892 USA. NR 567 TC 92 Z9 94 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0031-9333 J9 PHYSIOL REV JI Physiol. Rev. PD JUL PY 1991 VL 71 IS 3 BP 909 EP 949 PG 41 WC Physiology SC Physiology GA FU475 UT WOS:A1991FU47500008 PM 1711701 ER PT J AU Anderson, JE Goetz, CM McLaughlin, JL Suffness, M AF Anderson, J. E. Goetz, C. M. McLaughlin, J. L. Suffness, M. TI A Blind Comparison of Simple Bench-top Bioassays and Human Tumour Cell Cytotoxicities as Antitumor Prescreens SO PHYTOCHEMICAL ANALYSIS LA English DT Article DE Artemia salina; Agrobacterium tumefaciens; Lemna minor; cytotoxicity; antitumour prescreens; P-388 murinc leukaemia AB Simple bench-top bioassays involving brine shrimp lethality, Lemna frond proliferation, and the inhibition of crown gall tumours on potato discs, as well as the human tumour cell lines A-549 lung carcinoma, MCF-7 breast carcinoma and HT-29 colon adenocarcinoma, were compared for their accuracy to detect known in vivo (P-388) active antitumour agents supplied by the National Cancer Institute. The potato disc assay was the best and showed excellent correlation to in vivo activity (p = 0.008). The brine shrimp assay (p = 0.033) proved to be superior or equally as accurate as the in vitro human solid tumour cell lines (p = 0.033-0.334). The Lemna assay (p = 0.708) showed the poorest correlation. The brine shrimp and potato disc assays are suggested as convenient in-house prescreens to existing cytotoxicity or antitumour assays. C1 [Anderson, J. E.; Goetz, C. M.; McLaughlin, J. L.] Purdue Univ, Sch Pharm & Pharmacal Sci, Dept Med Chem & Pharmacognosy, W Lafayette, IN 47907 USA. [Suffness, M.] NCI, Dev Therapeut Program, NIH, Bethesda, MD 20892 USA. RP McLaughlin, JL (reprint author), Purdue Univ, Sch Pharm & Pharmacal Sci, Dept Med Chem & Pharmacognosy, W Lafayette, IN 47907 USA. FU National Cancer Institute, National Institutes of Health [CA 30909] FX This work was supported by Grant No. CA 30909 from the National Cancer Institute, National Institutes of Health. Thanks are due to Wenwen Ma for her help with the potato disc assay, and to Peggy Criswell and her staff at the Purdue Cancer Center, Cell Culture Laboratory for the cell culture data. NR 30 TC 127 Z9 137 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0958-0344 EI 1099-1565 J9 PHYTOCHEM ANALYSIS JI Phytochem. Anal. PD JUL PY 1991 VL 2 IS 3 BP 107 EP 111 DI 10.1002/pca.2800020303 PG 5 WC Biochemical Research Methods; Plant Sciences; Chemistry, Analytical SC Biochemistry & Molecular Biology; Plant Sciences; Chemistry GA V41IY UT WOS:000209541100002 ER PT J AU WILLIAMS, GM CORREA, P BARTSCH, H DIPPLE, A TANNENBAUM, S PECHACEK, T GREENWALD, P CARROLL, K MCKEOWNEYSSEN, G FELTON, J CAMPBELL, CC WATTENBERG, L UPTON, A HAUSEN, HZ HIGGINSON, J RANDERATH, K CONNEY, A AMES, B KROES, R AF WILLIAMS, GM CORREA, P BARTSCH, H DIPPLE, A TANNENBAUM, S PECHACEK, T GREENWALD, P CARROLL, K MCKEOWNEYSSEN, G FELTON, J CAMPBELL, CC WATTENBERG, L UPTON, A HAUSEN, HZ HIGGINSON, J RANDERATH, K CONNEY, A AMES, B KROES, R TI AMERICAN HEALTH FOUNDATIONS 20TH ANNIVERSARY INTERNATIONAL-SYMPOSIUM ON CAUSES AND PREVENTION OF CANCER - DECEMBER 11-12, 1989, NEW-YORK-CITY SO PREVENTIVE MEDICINE LA English DT Editorial Material ID HEMOGLOBIN ADDUCT; VITAMIN-C; CARCINOGENESIS; DNA; SMOKERS; RISK; PAPILLOMAVIRUSES; 4-AMINOBIPHENYL; EXPOSURE; BLADDER C1 LOUISIANA STATE UNIV,BATON ROUGE,LA 70803. INT AGCY RES CANC,F-69372 LYONS,FRANCE. NCI,FREDERICK CANC RES FACIL,FREDERICK,MD 21701. MIT,CAMBRIDGE,MA 02139. UNIV WESTERN ONTARIO,LONDON N6A 3K7,ONTARIO,CANADA. UNIV TORONTO,TORONTO M5S 1A1,ONTARIO,CANADA. UNIV CALIF LAWRENCE LIVERMORE NATL LAB,LIVERMORE,CA 94550. CORNELL UNIV,ITHACA,NY 14853. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. NYU MED CTR,NEW YORK,NY 10016. GERMAN CANC RES CTR,W-6900 HEIDELBERG 1,GERMANY. GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. BAYLOR UNIV,HOUSTON,TX 77030. RUTGERS STATE UNIV,NEW BRUNSWICK,NJ 08903. RP WILLIAMS, GM (reprint author), AMER HLTH FDN,1 DANA RD,VALHALLA,NY 10595, USA. NR 43 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD JUL PY 1991 VL 20 IS 4 BP 534 EP 547 DI 10.1016/0091-7435(91)90051-5 PG 14 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA FV005 UT WOS:A1991FV00500009 PM 1871081 ER PT J AU URBAN, JF KATONA, IM PAUL, WE FINKELMAN, FD AF URBAN, JF KATONA, IM PAUL, WE FINKELMAN, FD TI INTERLEUKIN-4 IS IMPORTANT IN PROTECTIVE IMMUNITY TO A GASTROINTESTINAL NEMATODE INFECTION IN MICE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE INTERLEUKIN-4; INTERLEUKIN-5; IGE; EOSINOPHIL; HELIGMOSOMOIDES-POLYGYRUS ID CELL-STIMULATORY FACTOR; POLYCLONAL IGE RESPONSE; FACTOR-I INTERLEUKIN-4; T-CELL; NIPPOSTRONGYLUS-BRASILIENSIS; MONOCLONAL-ANTIBODY; DIFFERENTIATION FACTOR; MURINE LEISHMANIASIS; SCHISTOSOMA-MANSONI; INTERFERON-GAMMA AB Parasitic helminths typically induce components of immediate-type hypersensitivity, including elevated serum IgE, eosinophilia, and mucosal mast cells. These responses are T-cell-dependent and associated with rapid expulsion of parasitic worms from a sensitized host; existing experimental systems have failed to define the precise role of cytokines in these responses. We report here that anti-interleukin 4 or anti-interleukin 4 receptor antibodies block the polyclonal IgE response to a parasitic nematode, Heligmosomoides polygyrus, and abrogate protective immunity to the infection. In contrast, anti-interleukin 5 antibody prevented H. polygyrus-induced eosinophilia but did not prevent protection. These data provide evidence that a specific cytokine affects the physiology and survival of a parasitic nematode in the host. C1 UNIFORMED SERV UNIV HLTH SCI,F EDWARD HEBERT SCH MED,DEPT PEDIAT,BETHESDA,MD 20888. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,F EDWARD HEBERT SCH MED,DEPT MED,BETHESDA,MD. RP URBAN, JF (reprint author), USDA ARS,BELTSVILLE AGR RES CTR,INST LIVESTOCK & POULTRY SCI,HELMINTH DIS LAB,BELTSVILLE,MD 20705, USA. OI Urban, Joseph/0000-0002-1590-8869 FU NIAID NIH HHS [AI-26150] NR 39 TC 308 Z9 309 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 JUL PY 1991 VL 88 IS 13 BP 5513 EP 5517 DI 10.1073/pnas.88.13.5513 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FU901 UT WOS:A1991FU90100008 PM 2062833 ER PT J AU STATES, DJ BOTSTEIN, D AF STATES, DJ BOTSTEIN, D TI MOLECULAR SEQUENCE ACCURACY AND THE ANALYSIS OF PROTEIN CODING REGIONS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SEQUENCE ERRORS; BAYESIAN ALIGNMENT; CODON USAGE ID DNA; GENES AB Molecular sequences, like all experimental data, have finite error rates. The impact of errors on the information content of molecular sequence data is dependent on the analytic paradigm used to interpret the data. We studied the impact of nucleic acid sequence errors on the ability to align predicted amino acid sequences with the sequences of related proteins. We found that with a simultaneous translation and alignment algorithm, identification of sequence homologies is resilient to the introduction of random errors. Proteins with > 30% sequence identity can be reliably recognized even in the presence of 1% frameshifting (insertion or deletion) error rates and 5% base substitution rates. Incorporation of prior knowledge about the location and characteristics of errors improves tolerance to error of amino acid sequence alignments. Similarly, inclusion of prior knowledge of biased codon utilization by yeast (Saccharomyces cerevisiae) allows reliable detection of correct reading frames in yeast sequences even in the presence of 5% substitution and 1% frameshift errors. C1 NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20892. STANFORD UNIV,MED CTR,SCH MED,DEPT GENET,STANFORD,CA 94305. NR 17 TC 41 Z9 43 U1 0 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 JUL PY 1991 VL 88 IS 13 BP 5518 EP 5522 DI 10.1073/pnas.88.13.5518 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FU901 UT WOS:A1991FU90100009 PM 2062834 ER PT J AU SCHEFFNER, M MUNGER, K BYRNE, JC HOWLEY, PM AF SCHEFFNER, M MUNGER, K BYRNE, JC HOWLEY, PM TI THE STATE OF THE P53 AND RETINOBLASTOMA GENES IN HUMAN CERVICAL-CARCINOMA CELL-LINES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN PAPILLOMAVIRUS TYPE-16; LARGE TUMOR-ANTIGEN; SV40 LARGE-T; SUSCEPTIBILITY GENE; SV40-TRANSFORMED CELLS; TRANSFORMING GENE; PROTEINS BIND; PRODUCT; DNA; TRANSCRIPTION AB Human cervical carcinoma cell lines that were either positive or negative for human papillomavirus (HPV) DNA sequences were analyzed for evidence of mutation of the p53 and retinoblastoma genes. Each of five HPV-positive cervical cancer cell lines expressed normal pRB and low levels of wild-type p53 proteins, which are presumed to be altered in function as a consequence of association with HPV E7 and E6 oncoproteins, respectively. In contrast, mutations were identified in the p53 and RB genes expressed in the C-33A and HT-3 cervical cancer cell lines, which lack HPV DNA sequences. Mutations in the p53 genes mapped to codon 273 and codon 245 in the C33-A and HT-3 cell lines, respectively, located in the highly conserved regions of p53, where mutations appear in a variety of human cancers. Mutations in RB occurred at splice junctions, resulting in in-frame deletions, affecting exons 13 and 20 in the HT-3 and C-33A cell lines, respectively. These mutations resulted in aberrant proteins that were not phosphorylated and were unable to complex with the adenovirus E1A oncoprotein. These results support the hypothesis that the inactivation of the normal functions of the tumor-suppressor proteins pRB and p53 are important steps in human cervical carcinogenesis, either by mutation or from complex formation with the HPV E6 and E7 oncoproteins. RP SCHEFFNER, M (reprint author), NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892, USA. RI Scheffner, Martin/K-2940-2012; OI Scheffner, Martin/0000-0003-2229-0128; Munger, Karl/0000-0003-3288-9935 NR 57 TC 744 Z9 756 U1 2 U2 11 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 JUL PY 1991 VL 88 IS 13 BP 5523 EP 5527 DI 10.1073/pnas.88.13.5523 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FU901 UT WOS:A1991FU90100010 PM 1648218 ER PT J AU KARLSTROM, AR LEVINE, RL AF KARLSTROM, AR LEVINE, RL TI COPPER INHIBITS THE PROTEASE FROM HUMAN IMMUNODEFICIENCY VIRUS-1 BY BOTH CYSTEINE-DEPENDENT AND CYSTEINE-INDEPENDENT MECHANISMS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SYNTHETIC HIV-1 PROTEASE; MIXED-FUNCTION OXIDATION; GLUTAMINE-SYNTHETASE; ASPARTIC PROTEASE; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; SITE; MUTAGENESIS; PROTEINASE; ENZYMES AB The protease of the human immunodeficiency virus is essential for replication of the virus, and the enzyme is therefore an attractive target for antiviral action. We have found that the viral protease is inhibited by approximately stoichiometric concentrations of copper or mercury ions. Inactivation by Cu2+ was rapid and not reversed by subsequent exposure to EDTA or dithiothreitol. Direct inhibition by Cu2+ required the presence of cysteine residue(s) in the protease. Thus, a synthetic protease lacking cysteine residues was not inhibited by exposure to copper. However, addition of dithiothreitol as an exogenous thiol rendered even the synthetic protease susceptible to inactivation by copper. Oxygen was not required for inactivation of either the wild-type or the synthetic protease. These results provide the basis for the design of novel types of protease inhibitors. RP KARLSTROM, AR (reprint author), NHLBI,BIOCHEM LAB,BLDG 3,ROOM 106,BETHESDA,MD 20892, USA. RI Levine, Rodney/D-9885-2011 NR 36 TC 66 Z9 67 U1 1 U2 10 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 JUL PY 1991 VL 88 IS 13 BP 5552 EP 5556 DI 10.1073/pnas.88.13.5552 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FU901 UT WOS:A1991FU90100016 PM 2062837 ER PT J AU VETTER, ML MARTINZANCA, D PARADA, LF BISHOP, JM KAPLAN, DR AF VETTER, ML MARTINZANCA, D PARADA, LF BISHOP, JM KAPLAN, DR TI NERVE GROWTH-FACTOR RAPIDLY STIMULATES TYROSINE PHOSPHORYLATION OF PHOSPHOLIPASE C-GAMMA-1 BY A KINASE-ACTIVITY ASSOCIATED WITH THE PRODUCT OF THE TRK PROTOONCOGENE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TYROSINE KINASE; GROWTH FACTOR; SIGNAL TRANSDUCTION; PC12 CELLS ID PC12 PHEOCHROMOCYTOMA CELLS; PDGF RECEPTOR; SIGNAL TRANSDUCTION; C-GAMMA; SEQUENCE; DIFFERENTIATION; ONCOGENE; SYSTEM; LINE; SRC AB Nerve growth factor (NGF) promotes the survival and differentiation of specific populations of neurons. The molecular mechanisms by which cells respond to NGF are poorly understood, but two clues have emerged recently. First, NGF rapidly stimulates tyrosine phosphorylation of several unidentified proteins in the NGF-responsive pheochromocytoma cell line PC12 [Maher, P. (1988) Proc. Natl. Acad. Sci. USA 85, 6788-6791]. Second, the protein-tyrosine kinase encoded by the protooncogene trk (p140(trk)), a member of the receptor class of tyrosine kinases, becomes activated and phosphorylated on tyrosine after NGF treatment of PC12 cells [Kaplan, D. R., Martin-Zanca, D. & Parada, L. F. (1991) Nature (London) 350, 158-160]. We now report that NGF rapidly induces tyrosine phosphorylation of phospholipase C-gamma-1 (PLC-gamma-1), and we present evidence that the responsible tyrosine kinase is either p140(trk) or a closely associated protein. Treatment of responsive cells with NGF elicited phosphorylation of PLC-gamma-1 on tyrosine and serine. PLC-gamma-1 immunoprecipitated from NGF-stimulated cells was phosphorylated in vitro by coprecipitating protein kinase activity, and the phosphorylations occurred principally on tyrosine. The responsible kinase could be depleted from cellular lysates by antibodies specific for p140(trk). This procedure also depleted a 140-kDa protein that normally coprecipitated with PLC-gamma-1 and became phosphorylated on tyrosine in vivo in response to NGF. Analysis of tryptic peptides from PLC-gamma-1 indicated that the residues phosphorylated in vitro by p140(trk)-associated kinase activity were largely congruent with those phosphorylated in vivo after NGF treatment. Our findings identify PLC-gamma-1 as a likely substrate for the trk-encoded tyrosine kinase, and they provide a link between NGF-dependent activation of p140(trk) and the stimulation of intracellular second messenger pathways. C1 UNIV CALIF SAN FRANCISCO,GEORGE WILLIAMS HOOPER FDN,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT MICROBIOL & IMMUNOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,PROGRAM NEUROSCI,SAN FRANCISCO,CA 94143. NCI,FREDERICK CANC RES & DEV CTR,EUKARYOT SIGNAL TRANSDUCT GRP,FREDERICK,MD 21701. NCI,ADV BIOSCI LABS,BASIC RES PROGRAM,MOLEC EMBRYOL GRP,FREDERICK,MD 21701. RI Parada, luis/B-9400-2014 FU NCI NIH HHS [CA 44338]; PHS HHS [N01-C0-74101] NR 32 TC 221 Z9 222 U1 0 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 JUL PY 1991 VL 88 IS 13 BP 5650 EP 5654 DI 10.1073/pnas.88.13.5650 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FU901 UT WOS:A1991FU90100036 PM 1712104 ER PT J AU KARSCHIN, A HO, BY LABARCA, C ELROYSTEIN, O MOSS, B DAVIDSON, N LESTER, HA AF KARSCHIN, A HO, BY LABARCA, C ELROYSTEIN, O MOSS, B DAVIDSON, N LESTER, HA TI HETEROLOGOUSLY EXPRESSED SEROTONIN-1A RECEPTORS COUPLE TO MUSCARINIC K+ CHANNELS IN HEART SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE VACCINIA VIRUS EXPRESSION; GUANINE NUCLEOTIDE-BINDING PROTEINS; 7-HELIX RECEPTORS; ATRIAL CELLS; ACETYLCHOLINE ID GTP-BINDING PROTEINS; ARACHIDONIC-ACID METABOLITES; ATRIAL CELLS; POTASSIUM CHANNELS; ADENYLATE-CYCLASE; VACCINIA VIRUS; ALPHA-SUBUNIT; ACTIVATION; ACETYLCHOLINE; INHIBITION AB In cardiac atrial cells, muscarinic acetylcholine receptors activate a K+ current directly via a guanine nucleotide-binding protein (G protein). Serotonin type 1A receptors may activate a similar pathway in hippocampal neurons. To develop a system in which receptor/G protein/K+ channel coupling can be experimentally manipulated, we have used a highly efficient recombinant vaccinia virus vector system to express human serotonin 1A receptors in primary cultures of rat atrial myocytes. The expressed 1A receptors activated the inwardly rectifying K+ conductance that is normally activated by the endogenous muscarinic acetylcholine receptors. Maximal responses to either agonist occluded further activation by the other agonist. The average activation time constants for serotonin were about 5 times slower than for acetylcholine. The data support suggestions that the intracellular signaling pathway from seven-helix receptors to G proteins and directly to ion channels is widespread in excitable cells. After a fraction of the G proteins are activated irreversibly by guanosine 5'-[gamma-thio]triphosphate, subsequent transduction proceeds more efficiently. One possible interpretation is that multiple G-protein molecules are required to activate each channel. Vaccinia virus expression vectors are thus useful for expressing seven-helix receptors in primary cultures of postmitotic cells and have provided a heterologous expression system for the signaling pathway from seven-helix receptors to G proteins and directly to ion channels. C1 NIH,INST ALLERGY & INFECT DIS,VIRAL DIS LAB,BETHESDA,MD 20892. RP KARSCHIN, A (reprint author), CALTECH,DIV BIOL 156-29,PASADENA,CA 91125, USA. FU NIGMS NIH HHS [GM10991, GM29836] NR 40 TC 46 Z9 46 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 JUL PY 1991 VL 88 IS 13 BP 5694 EP 5698 DI 10.1073/pnas.88.13.5694 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FU901 UT WOS:A1991FU90100045 PM 1905814 ER PT J AU BRENNER, B YU, LC CHALOVICH, JM AF BRENNER, B YU, LC CHALOVICH, JM TI PARALLEL INHIBITION OF ACTIVE FORCE AND RELAXED FIBER STIFFNESS IN SKELETAL-MUSCLE BY CALDESMON - IMPLICATIONS FOR THE PATHWAY TO FORCE GENERATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RABBIT PSOAS FIBERS; ACTOMYOSIN ATPASE ACTIVITY; RAY-DIFFRACTION PATTERNS; MYOSIN SUBFRAGMENT-1; TROPONIN-TROPOMYOSIN; HEAVY-MEROMYOSIN; F-ACTIN; CONTAINING FILAMENTS; REGULATED ACTIN; BINDING AB In recent hypotheses on muscle contraction, myosin cross-bridges cycle between two types of actin-bound configuration. These two configurations differ greatly in the stability of their actin-myosin complexes ("weak-binding" vs. "strong-binding"), and force generation or movement is the result of structural changes associated with the transition from the weak-binding (preforce generating) configuration to strong-binding (force producing) configuration [cf. Eisenberg, E. & Hill, T. L. (1985) Science 227, 999-1006]. Specifically, in this concept, the main force-generating states are only accessible after initial cross-bridge attachment in a weak-binding configuration. It has been shown that strong and weak cross-bridge attachment can occur in muscle fibers [Brenner, B., Schoenberg, M., Chalovich, J. M., Greene, L. E. & Eisenberg, E. (1982) Proc. Natl. Acad. Sci. USA 79, 7288-7291]. However, there has been no evidence that attachment in the weak-binding states represents an essential step leading to force generation. It is shown here that caldesmon can be used to selectively inhibit attachment of weak-binding cross-bridges in skeletal muscle. Such inhibition causes a parallel decrease in active force, while the kinetics of cross-bridge turnover are unchanged by this procedure. This suggests that (i) cross-bridge attachment in the weak-binding states is specific and (ii) force production can only occur after cross-bridges have first attached to actin in a weakly bound, nonforce-generating configuration. C1 NIAMSD,PHYS BIOL LAB,BETHESDA,MD 20892. E CAROLINA UNIV,DEPT BIOCHEM,GREENVILLE,NC 27858. RP BRENNER, B (reprint author), UNIV ULM,DEPT GEN PHYSIOL,W-7900 ULM,GERMANY. OI Chalovich, Joseph/0000-0002-1243-4055 FU NIAMS NIH HHS [R01 AR035216, AR35216, AR40540-01A1] NR 63 TC 82 Z9 82 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 JUL PY 1991 VL 88 IS 13 BP 5739 EP 5743 DI 10.1073/pnas.88.13.5739 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FU901 UT WOS:A1991FU90100054 PM 2062853 ER PT J AU HOCHACHKA, PW BIANCONCINI, MSC PARKHOUSE, WS DOBSON, GP AF HOCHACHKA, PW BIANCONCINI, MSC PARKHOUSE, WS DOBSON, GP TI ON THE ROLE OF ACTOMYOSIN ATPASES IN REGULATION OF ATP TURNOVER RATES DURING INTENSE EXERCISE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE METABOLIC CONTROL; ENERGY COUPLING; MUSCLE METABOLISM; FLUX CONTROL; FIBER-TYPE METABOLISM ID SKELETAL-MUSCLE; OXIDATIVE-PHOSPHORYLATION; RESPIRATORY SYSTEM; METABOLISM; PERFORMANCE; ENERGETICS; LOCOMOTION; PYRUVATE; LACTATE; TWITCH AB Actomyosin ATPase is the dominant ATP sink during muscle work. Its catalytic capacities in fast-twitch oxidative glycolytic fibers have long been known to exceed by about 3-fold those of slow-twitch oxidative fibers, but the relative contributions to control of metabolic rates during exercise have never been closely examined. We compared fast-twitch oxidative glycolytic and slow-twitch oxidative fibers that displayed similar mitochondrial abundance (similar activities of mitochondrial marker enzymes). During short-term, but near maximum, aerobic exercise, fast-twitch oxidative glycolytic fibers displayed ATP turnover rates that were 2-4 times higher than for slow-twitch oxidative fibers (despite similar mitochondrial metabolic capacities), implying a large ATPase contribution to control of maximum metabolic rate. Fluxes through the ATP arrow pointing right over arrow pointing left ADP + P(i) cycle were extremely well regulated; at the lower limit, the forward flux exceeded the backward flux by only 0.06%, whereas at the upper limit, ATPase rates exceeded ATP synthesis rates by 0.12%. This very high precision of energy coupling could not be easily explained by standard metabolic regulation models. C1 NIAAA,METAB LAB,ROCKVILLE,MD 20852. SIMON FRASER UNIV,DEPT KINESIOL,BURNABY V5A 1S6,BC,CANADA. RP HOCHACHKA, PW (reprint author), UNIV BRITISH COLUMBIA,DEPT ZOOL,VANCOUVER V6T 1Z4,BC,CANADA. NR 34 TC 26 Z9 26 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 JUL PY 1991 VL 88 IS 13 BP 5764 EP 5768 DI 10.1073/pnas.88.13.5764 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FU901 UT WOS:A1991FU90100059 PM 1829528 ER PT J AU BALASUNDARAM, D TABOR, CW TABOR, H AF BALASUNDARAM, D TABOR, CW TABOR, H TI SPERMIDINE OR SPERMINE IS ESSENTIAL FOR THE AEROBIC GROWTH OF SACCHAROMYCES-CEREVISIAE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE POLYAMINES; S-ADENOSYLMETHIONINE DECARBOXYLASE; SPE2 ID S-ADENOSYLMETHIONINE DECARBOXYLASE; ORNITHINE DECARBOXYLASE; YEAST SACCHAROMYCES; CHITIN SYNTHESIS; ACTIN; POLYAMINES; MUTANTS; CYTOKINESIS; INDUCTION; CELLS AB A null mutation in the SPE2 gene of Saccharomyces cerevisiae, encoding S-adenosylmethionine decarboxylase, results in cells with no detectable S-adenosylmethionine decarboxylase, spermidine, and spermine. This mutant has an absolute requirement for spermidine or spermine for growth; this requirement is not satisfied by putrescine. Polyamine-depleted cells show a number of microscopic abnormalities that are similar to those reported for several cell division cycle (cdc) and actin mutants. These include a striking increase in cell size, a marked decrease in budding, accumulation of vesicle-like bodies, absence of specific localization of chitin-like material, and abnormal distribution of actin-like material. The absolute requirement for polyamines for growth and the microscopic abnormalities are not seen if the cultures are grown under anaerobic conditions. RP NIDDKD, BIOCHEM PHARMACOL LAB, BLDG 8, ROOM 223, BETHESDA, MD 20892 USA. NR 43 TC 89 Z9 90 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL PY 1991 VL 88 IS 13 BP 5872 EP 5876 DI 10.1073/pnas.88.13.5872 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FU901 UT WOS:A1991FU90100081 PM 2062864 ER PT J AU SCHIRMER, EC WYATT, LS YAMANISHI, K RODRIGUEZ, WJ FRENKEL, N AF SCHIRMER, EC WYATT, LS YAMANISHI, K RODRIGUEZ, WJ FRENKEL, N TI DIFFERENTIATION BETWEEN 2 DISTINCT CLASSES OF VIRUSES NOW CLASSIFIED AS HUMAN HERPESVIRUS-6 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EXANTHEM SUBITUM; MOLECULAR EPIDEMIOLOGY; T-CELLS; INFECTION; ANTIBODY; HHV-6; HBLV; SALIVA; DNA; TRANSPLANTATION AB Human herpesvirus 6 (HHV-6) causes exanthem subitum (ES, roseola infantum), a childhood disease characterized by high fever and skin rash. We have analyzed restriction enzyme cleavage patterns of the DNAs of ES virus isolates from Japan and the United States. The patterns of all the ES viral DNAs were highly conserved, except for variable sequences within the terminal repeat sequences. They resembled closely the restriction enzyme patterns of the Z29 strain of HHV-6 but were distinct from those of the U1102 strain. That all ES isolates were closely related whereas the U1102 patterns were very different suggests that the U1102 strain represents a distinct virus. Moreover, the ES isolates all resembled the Z29 strain and not the U1102 strain with respect to reactivity with HHV-6 monoclonal antibodies. These findings provide evidence for the existence of two distinct classes of viruses previously classified as HHV-6. Whereas the Z29-like viruses are involved in ES infections, the association of the U1102-like viruses with human disease has yet to be determined. C1 NIAID, VIRAL DIS LAB, BLDG 4, BETHESDA, MD 20892 USA. CHILDRENS HOSP, DEPT INFECT DIS, WASHINGTON, DC 20011 USA. OSAKA UNIV, DEPT VIROL, MICROBIAL DIS RES INST, SUITA, OSAKA 565, JAPAN. NR 34 TC 171 Z9 174 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL PY 1991 VL 88 IS 13 BP 5922 EP 5926 DI 10.1073/pnas.88.13.5922 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FU901 UT WOS:A1991FU90100091 PM 1648234 ER PT J AU SITBON, M DAURIOL, L ELLERBROK, H ANDRE, C NISHIO, J PERRYMAN, S POZO, F HAYES, SF WEHRLY, K TAMBOURIN, P GALIBERT, F CHESEBRO, B AF SITBON, M DAURIOL, L ELLERBROK, H ANDRE, C NISHIO, J PERRYMAN, S POZO, F HAYES, SF WEHRLY, K TAMBOURIN, P GALIBERT, F CHESEBRO, B TI SUBSTITUTION OF LEUCINE FOR ISOLEUCINE IN A SEQUENCE HIGHLY CONSERVED AMONG RETROVIRAL ENVELOPE SURFACE GLYCOPROTEINS ATTENUATES THE LYTIC EFFECT OF THE FRIEND MURINE LEUKEMIA-VIRUS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ERYTHROLEUKEMIA; HEMOLYTIC ANEMIA; LONG TERMINAL REPEAT; RETROVIRAL PATHOGENESIS ID LONG TERMINAL REPEAT; FOCUS-FORMING VIRUS; NUCLEOTIDE-SEQUENCE; DISEASE SPECIFICITY; IMMUNODEFICIENCY DISEASE; TEMPERATURE SENSITIVITY; MOLECULAR-CLONING; ENV GENE; 3' END; MOLONEY AB Friend murine leukemia virus is a replication-competent retrovirus that contains no oncogene and that exerts lytic and leukemogenic properties. Thus, newborn mice inoculated with Friend murine leukemia virus develop severe early hemolytic anemia before appearance of erythroleukemia. To identify the retroviral determinants regulating these effects, we used chimeric infectious constructions and site-directed point mutations between a virulent Friend murine leukemia virus strain and a naturally occurring variant attenuated in lytic and leukemogenic effects. We found that severe hemolytic anemia was always associated with higher numbers of blood reticulocytes with budding retroviral particles. Furthermore, a remarkably conservative leucine to isoleucine change in the extracellular SU component of the retroviral envelope was sufficient to attenuate this lytic effect. Also, this leucine at position 348 of the envelope precursor protein was located within the only stretch of five amino acids that is conserved in the extracellular SU component of all murine, feline, and primate type C and type D retroviral envelopes. This observation suggested an important structural function for this yet undescribed conserved sequence of the envelope. Lastly, we observed that lytic and leukemogenic effects were attenuated by a deletion of a second repeat in the transcriptional enhancer region of the viral long terminal repeats of the variant strain. C1 NIAID,ROCKY MT LABS,VECTORS & PATHOGENS LAB,HAMILTON,MT 59840. GENSET,F-75005 PARIS,FRANCE. NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. HOP ST LOUIS,CTR HAYEM,HEMATOL EXPTL LAB,F-75010 PARIS,FRANCE. RP SITBON, M (reprint author), INSERM,U152,INST COCHIN GENET MOLEC,F-75014 PARIS,FRANCE. RI Sitbon, Marc/A-6771-2010 OI Sitbon, Marc/0000-0003-3616-2338 NR 46 TC 32 Z9 32 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 JUL PY 1991 VL 88 IS 13 BP 5932 EP 5936 DI 10.1073/pnas.88.13.5932 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FU901 UT WOS:A1991FU90100093 PM 2062871 ER PT J AU HARAGUCHI, K RODBELL, M AF HARAGUCHI, K RODBELL, M TI CARBACHOL-ACTIVATED MUSCARINIC (M1 AND M3) RECEPTORS TRANSFECTED INTO CHINESE-HAMSTER OVARY CELLS INHIBIT TRAFFICKING OF ENDOSOMES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE FLUID-PHASE ENDOCYTOSIS; G-PROTEINS; CALCIUM; FUSION; SIGNAL TRANSDUCTION ID ACETYLCHOLINE-RECEPTORS; PLASMA-MEMBRANE; FREE SYSTEM; MEDIATED ENDOCYTOSIS; VESICLES; TRANSPORT; PROTEIN; FUSION; RECONSTITUTION; PATHWAYS AB We examined the effects of isoproterenol and carbachol on fluid-phase endocytosis by Chinese hamster ovary (CHO) cells transfected with beta-adrenergic, M1, or M3 cholinergic receptors. Isoproterenol increased cAMP production and carbachol increased intracellular Ca, indicating successful expression of the receptor genes and coupling to typical signal transduction pathways. Carbachol inhibited the uptake of horseradish peroxidase (HRP) or Lucifer yellow (markers of fluid-phase endocytosis) in both M1- and M3-containing cells but not in wild-type cells, whereas isoproterenol did not affect pinocytosis in cells transfected with beta-adrenergic receptors. Carbachol inhibited the transit of HRP from an exchangeable pool to a nonexchangeable pool by a latent process requiring minimally 5 min of incubation. During the latent period, only one peak of low-density HRP-containing vesicles was found on Percoll gradients; after 5 min, HRP appeared in both high- and low-density vesicles. Carbachol-treated cells contained less HRP in the high-density fraction enriched in lysosomal markers. Early endosomes from CHO cells labeled for 5 min with HRP underwent fusion to make a more dense population of vesicles in the presence of ATP and KCl at 37-degrees-C but not at 4-degrees-C. The fused material contained increased levels of G proteins as detected either by ADP ribosylation with appropriate toxins or by immunoblotting with specific antibodies. These findings suggest that GTP binding proteins are internalized in endocytic vesicles and enter into a complex trafficking process involving fusion with other vesicular compartments. Trafficking of endosomes to these compartments is inhibited by activated MI and M3 muscarinic receptors in CHO cells. C1 NIEHS, SIGNAL TRANSDUCT SECT, RES TRIANGLE PK, NC 27709 USA. NR 38 TC 11 Z9 11 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL PY 1991 VL 88 IS 14 BP 5964 EP 5968 DI 10.1073/pnas.88.14.5964 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FW761 UT WOS:A1991FW76100006 PM 1906173 ER PT J AU LAMB, CA YEWDELL, JW BENNINK, JR CRESSWELL, P AF LAMB, CA YEWDELL, JW BENNINK, JR CRESSWELL, P TI INVARIANT CHAIN TARGETS HLA CLASS-II MOLECULES TO ACIDIC ENDOSOMES CONTAINING INTERNALIZED INFLUENZA-VIRUS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ANTIGEN PROCESSING; MAJOR HISTOCOMPATIBILITY COMPLEX ID ANTIGEN PRESENTATION PATHWAYS; CELL-SURFACE EXPRESSION; TOXIC LYMPHOCYTES-T; MHC CLASS-II; MONOCLONAL-ANTIBODIES; ENDOPLASMIC-RETICULUM; ALPHA-CHAIN; BETA-CHAIN; IA; TRANSPORT AB The role of the HLA class II-associated invariant chain in the intracellular trafficking of HLA-DR molecules was examined in a transient expression system using HeLa cells. In the absence of alpha and beta-polypeptides, invariant chain was retained in the endoplasmic reticulum (ER). In the absence of invariant chain, intracellular alpha-beta heterodimers could be detected only in the ER and the Golgi apparatus. However, when alpha and beta-subunits were coexpressed with invariant chain, HLA-DR molecules were detectable in peripheral cytoplasmic vesicles, which also contained invariant chain. In addition, an antibody directed to an acid-induced conformational determinant on the influenza hemagglutinin molecule detected internalized influenza virus in the HLA-DR-containing vesicles. These findings provide direct evidence that the invariant chain targets class II molecules to an acidic endosomal compartment and that this compartment, long suspected to be the site of antigen processing, is the site where class II molecules interact with natural antigen. C1 DUKE UNIV,MED CTR,DEPT MICROBIOL & IMMUNOL,DURHAM,NC 27710. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. RI yewdell, jyewdell@nih.gov/A-1702-2012 FU NIAID NIH HHS [AI23081] NR 43 TC 147 Z9 147 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 JUL PY 1991 VL 88 IS 14 BP 5998 EP 6002 DI 10.1073/pnas.88.14.5998 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FW761 UT WOS:A1991FW76100013 PM 2068076 ER PT J AU DAMERON, CT WINGE, DR GEORGE, GN SANSONE, M HU, S HAMER, D AF DAMERON, CT WINGE, DR GEORGE, GN SANSONE, M HU, S HAMER, D TI A COPPER THIOLATE POLYNUCLEAR CLUSTER IN THE ACE1 TRANSCRIPTION FACTOR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE METALLOTHIONEIN; METAL SENSOR; METAL CLUSTER; GENE REGULATION ID X-RAY ABSORPTION; METALLOTHIONEIN GENE-TRANSCRIPTION; DNA-BINDING PROTEIN; YEAST METALLOTHIONEIN; EXPRESSION; COMPLEXES; PRODUCT AB ACE1 is the transcriptional activator of the metallothionein (CUP] locus) gene in Saccharomyces cerevisiae. Previous data had implicated the N-terminal domain of ACE1 as responsible for the Cu-dependent specific DNA binding. An expression system in Escherichia coli was constructed to enable the isolation of an ACE1 domain containing the DNA and Cu-binding regions. Here we report the purification and characterization of the Cu-ACE1 truncated molecule. Spectroscopic techniques showed that ACE1 contains an unusual type of DNA binding structure that is based on a polynuclear Cu(I)-cysteinyl thiolate cluster. The cluster consists of six or seven Cu(I) ions coordinated to cysteinyl thiolates in a trigonal geometry distorted from planarity. The Cu(I)-cysteine cluster of Cu-ACE1 exhibits structural properties analogous to the Cu(I)-thiolate polynuclear cluster in yeast Cu-metallothionein itself, suggesting an unusual mechanism for the evolution of this regulatory factor. The Cu cluster organizes and stabilizes the conformation of the N-terminal domain of ACE1 for specific DNA binding. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. UNIV UTAH,MED CTR,SALT LAKE CITY,UT 84132. EXXON RES & ENGN CO,ANNANDALE,NJ 08801. RI George, Graham/E-3290-2013 FU NIEHS NIH HHS [ES 03817] NR 21 TC 103 Z9 103 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 JUL PY 1991 VL 88 IS 14 BP 6127 EP 6131 DI 10.1073/pnas.88.14.6127 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FW761 UT WOS:A1991FW76100039 PM 2068093 ER PT J AU KANG, CY NARA, P CHAMAT, S CARALLI, V RYSKAMP, T HAIGWOOD, N NEWMAN, R KOHLER, H AF KANG, CY NARA, P CHAMAT, S CARALLI, V RYSKAMP, T HAIGWOOD, N NEWMAN, R KOHLER, H TI EVIDENCE FOR NON-V3-SPECIFIC NEUTRALIZING ANTIBODIES THAT INTERFERE WITH GP120/CD4 BINDING IN HUMAN-IMMUNODEFICIENCY-VIRUS 1-INFECTED HUMANS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HUMAN ANTI-GP120 ANTIBODY; HUMAN IMMUNODEFICIENCY VIRUS-1 NEUTRALIZATION ID ENVELOPE GLYCOPROTEIN; MONOCLONAL-ANTIBODY; TYPE-1; HIV-1; CD4; EPITOPE; CHIMPANZEES; ASSAY; SERA; AIDS AB Total anti-gp120 antibodies (total anti-gpl20 Abs) were purified from a pool of four human immunodeficiency virus-positive (HIV+) sera by affinity chromatography on a gp120SF2-Sepharose column and exhibited both type- and group-specific neutralizing activities. To dissect the epitope specificity of the group-specific neutralizing antibodies, CD4 attachment site-specific antibodies (CD4-site Abs) were isolated from total anti-gp120 Abs by using a CD4-blocked gp120SF2-Sepharose column. The CD4-site Abs exhibited group-specific neutralizing activities. Another approach to dissecting type-and group-specific neutralizing activities of total anti-gp120 Abs was to separate the third variable region (V3)-specific antibodies (V3-region Abs) from non-V3-region-specific antibodies (non-V3 Abs). The results indicated that V3-region Abs exhibited type-specific neutralizing activities, whereas non-V3 Abs exhibited group-specific neutralizing activities. By comparing the neutralizing activities of V3-region Abs to those of non-V3 Abs, we concluded that V3-region Abs are more effective than non-V3 Abs in neutralizing a specific HIV isolate. Collectively, this study indicates that group-specific neutralizing anti-gp120 antibodies are specific for the CD4 attachment site. C1 NCI,FREDERICK,MD 21701. CHIRON CORP,EMERYVILLE,CA 94608. RP KANG, CY (reprint author), IDEC PHARMACEUT CORP,11099 N TORREY PINES RD,160,LA JOLLA,CA 92037, USA. FU PHS HHS [1R43A129770-01] NR 28 TC 103 Z9 103 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 JUL PY 1991 VL 88 IS 14 BP 6171 EP 6175 DI 10.1073/pnas.88.14.6171 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FW761 UT WOS:A1991FW76100048 PM 2068099 ER PT J AU SCAVO, L SHULDINER, AR SERRANO, J DASHNER, R ROTH, J DEPABLO, F AF SCAVO, L SHULDINER, AR SERRANO, J DASHNER, R ROTH, J DEPABLO, F TI GENES ENCODING RECEPTORS FOR INSULIN AND INSULIN-LIKE GROWTH FACTOR-I ARE EXPRESSED IN XENOPUS-OOCYTES AND EMBRYOS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTEIN-SYNTHESIS; TYROSINE KINASE; BETA-SUBUNIT; STIMULATION; LAEVIS; RNA; DIFFERENTIATION; PHOSPHORYLATION; LIGAND; CDNA AB Insulin and insulin-like growth factor I (IGF-I) initiate their metabolic, growth, and differentiation effects through binding to the insulin receptor and the IGF-I receptor, two members of the tyrosine kinase family of receptors. To study the role of these peptides and receptors in early development, we used the polymerase chain reaction and embryo-derived RNA to generate partial cDNA sequences of the insulin receptor and IGF-I receptor from the amphibian Xenopus laevis. Three unique tyrosine kinase-related sequences were obtained. Two of the nucleotide sequences, XTK 1a and XTK 1b, corresponded to peptides that share 92% amino acid identity, and each is 89% identical to the human insulin receptor. The third sequence, XTK 2, corresponds to a peptide that has 92% amino acid identity with the human IGF-I receptor but only 80% identity with XTK 1a and XTK 1b. On the basis of these similarities, the pattern of conserved amino acids, and the tetraploid nature of the Xenopus genome, we suggest that XTK la and XTK 1b most likely represent the product of two different nonallelic insulin receptor genes, while XTK 2 may be one of the probable two Xenopus IGF-I receptor genes. By reverse transcription-polymerase chain reaction and gene-specific hybridization, expression of the three XTK sequences was detected in the oocyte, unfertilized egg, and embryos through gastrulation, neurulation, and tailbud stages. Competition binding assays with Xenopus membrane preparations demonstrated insulin receptors and IGF-I receptors in older tadpoles. IGF-I receptors were also present in oocytes, eggs, and gastrula embryos. By contrast, insulin binding was present but atypical in oocytes and was barely detected in eggs and gastrula embryos. The expression of receptors for insulin and IGF-I in early Xenopus embryos and their apparent distinct developmental regulation suggest that these molecules and their ligands may be important in early Xenopus development. RP SCAVO, L (reprint author), NIDDKD,DIABET BRANCH,BLDG 10,ROOM 85-243,BETHESDA,MD 20892, USA. NR 36 TC 66 Z9 68 U1 0 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 JUL PY 1991 VL 88 IS 14 BP 6214 EP 6218 DI 10.1073/pnas.88.14.6214 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FW761 UT WOS:A1991FW76100057 PM 1648732 ER PT J AU HULTSCH, T ALBERS, MW SCHREIBER, SL HOHMAN, RJ AF HULTSCH, T ALBERS, MW SCHREIBER, SL HOHMAN, RJ TI IMMUNOPHILIN LIGANDS DEMONSTRATE COMMON FEATURES OF SIGNAL TRANSDUCTION LEADING TO EXOCYTOSIS OR TRANSCRIPTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE RAT BASOPHILIC LEUKEMIA CELLS; CYCLOSPORINE-A; FK506; RAPAMYCIN; CYCLOPHILIN ID PEPTIDYL-PROLYL ISOMERASE; T-CELL ACTIVATION; MAST-CELLS; IMMUNOSUPPRESSANT FK506; MACROLIDES FK-506; CYCLOSPORINE-A; IGE; RECEPTOR; RAPAMYCIN; DISTINCT AB Investigations of the actions and interactions of the immunophilin ligands FK506, cyclosporin A (CsA), rapamycin, and 506BD suggest that complexes of FK506 with an FK506-binding protein or of CsA with a cyclophilin (CsA-binding protein) inhibit the T-cell receptor-mediated signal transduction that results in the transcription of interleukin 2. Now we report an identical spectrum of activities of FK506, CsA, rapamycin, and 506BD on IgE receptor-mediated signal transduction that results in exocytosis of secretory granules from the rat basophilic leukemia cell line RBL-2H3, a mast cell model. Both FK506 and CsA inhibit receptor-mediated exocytosis (CsA IC50 = 200 nM; FK506 IC50 = 2 nM) without affecting early receptor-associated events (hydrolysis of phosphatidylinositol, synthesis and release of eicosanoids, uptake of Ca2+). In contrast, rapamycin and 506BD, which share common structural elements with FK506, by themselves have no effect on IgE receptor-mediated exocytosis. Both compounds, however, prevent inhibition by FK506 but not by CsA. Affinity chromatography with FK506, CsA, and rapamycin matrices indicates that the same set of immunophilins present in RBL-2H3 cells have been found in Jurkat T cells and calf thymus; however, the relative amounts of these proteins differ in the two cell types. These results suggest the existence of a common step in cytoplasmic signaling in T cells and mast cells that may be part of a general signaling mechanism. C1 NIAID,CLIN INVEST LAB,ALLERG DIS SECT,BETHESDA,MD 20892. HARVARD UNIV,DEPT CHEM,CAMBRIDGE,MA 02138. FU NIGMS NIH HHS [GM38627] NR 33 TC 132 Z9 133 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 JUL PY 1991 VL 88 IS 14 BP 6229 EP 6233 DI 10.1073/pnas.88.14.6229 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FW761 UT WOS:A1991FW76100060 PM 1712484 ER PT J AU DAWSON, VL DAWSON, TM LONDON, ED BREDT, DS SNYDER, SH AF DAWSON, VL DAWSON, TM LONDON, ED BREDT, DS SNYDER, SH TI NITRIC-OXIDE MEDIATES GLUTAMATE NEUROTOXICITY IN PRIMARY CORTICAL CULTURES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ENDOTHELIUM-DERIVED RELAXING FACTOR; N-METHYL-D-ASPARTATE ID MONOMETHYL-L-ARGININE; RAT ANOCOCCYGEUS MUSCLE; NADPH-DIAPHORASE; ENDOTHELIAL-CELLS; RELAXING FACTOR; NEUROPEPTIDE-Y; TARGET-CELLS; NEURONS; BIOSYNTHESIS; STIMULATION AB Nitric oxide (NO) mediates several biological actions, including relaxation of blood vessels, cytotoxicity of activated macrophages, and formation of cGMP by activation of glutamate receptors in cerebellar slices. Nitric oxide synthase (EC 1.14.23.-) immunoreactivity is colocalized with nicotinamide adenine di-nucleotide phosphate diaphorase in neurons that are uniquely resistant to toxic insults. We show that the nitric oxide synthase inhibitors, N-omega-nitro-L-arginine (EC50 = 20 mu-M) and N-omega-monomethyl-L-arginine (EC50 = 170-mu-M), prevent neurotoxicity elicited by N-methyl-D-aspartate and related excitatory amino acids. This effect is competitively reversed by L-arginine. Depletion of the culture medium of arginine by arginase or arginine-free growth medium completely attenuates N-methyl-D-aspartate toxicity. Sodium nitroprusside, which spontaneously releases NO, produces dose-dependent cell death that parallels cGMP formation. Hemoglobin, which complexes NO, prevents neurotoxic effects of both N-methyl-D-aspartate and sodium nitroprusside. These data establish that NO mediates the neurotoxicity of glutamate. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,725 N WOLFE ST,BALTIMORE,MD 21205. NIDA,ADDICT RES CTR,NEUROPHARMACOL LAB,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL & MOLEC SCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT,BALTIMORE,MD 21205. RI Bredt, David/J-4872-2012; OI Dawson, Valina/0000-0002-2915-3970 FU NIDA NIH HHS [DA-00074, DA-00266, DA-271-90-7408] NR 35 TC 1972 Z9 2009 U1 2 U2 27 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 JUL PY 1991 VL 88 IS 14 BP 6368 EP 6371 DI 10.1073/pnas.88.14.6368 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FW761 UT WOS:A1991FW76100088 PM 1648740 ER PT J AU TSAI, M TAKEISHI, T THOMPSON, H LANGLEY, KE ZSEBO, KM METCALFE, DD GEISSLER, EN GALLI, SJ AF TSAI, M TAKEISHI, T THOMPSON, H LANGLEY, KE ZSEBO, KM METCALFE, DD GEISSLER, EN GALLI, SJ TI INDUCTION OF MAST-CELL PROLIFERATION, MATURATION, AND HEPARIN SYNTHESIS BY THE RAT C-KIT LIGAND, STEM-CELL FACTOR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DEVELOPMENTAL BIOLOGY; W AND SL LOCI; CELL CELL INTERACTION; HISTAMINE; INTERLEUKIN-3 ID CONNECTIVE-TISSUE-TYPE; TYROSINE KINASE RECEPTOR; MOUSE BONE-MARROW; GROWTH-FACTOR; SI-LOCUS; W-LOCUS; MULTIPLE CYTOKINES; PROTO-ONCOGENE; IDENTIFICATION; INVITRO AB We investigated the effects of a newly recognized multifunctional growth factor, the c-kit ligand stem cell factor (SCF), on mouse mast cell proliferation and phenotype. Recombinant rat SCF164 (rrSCF164) induced the development of large numbers of dermal mast cells in normal mice in vivo. Many of these mast cells had features of "connective tissue-type mast cells" (CTMC), in that they were reactive both with the heparin-binding fluorescent dye berberine sulfate and with safranin. In vitro, rrSCF164 induced the proliferation of cloned interleukin 3 (IL-3)-dependent mouse mast cells and primary populations of IL-3-dependent, bone marrow-derived cultured mast cells (BMCMC), which represent immature mast cells, and purified peritoneal mast cells, which represent a type of mature CTMC. BMCMC maintained in rrSCF164 not only proliferated but also matured. Prior to exposure to rrSCF164, the BMCMC were alcian blue positive, safranin negative, and berberine sulfate negative; had a histamine content of 0.08 +/- 0.02. pg per cell; and incorporated [S-35]sulfate into chondroitin sulfates. After 4 wk in rrSCF164 the BMCMC were predominantly safranin positive and berberine sulfate positive, had a histamine content of 2.23 +/- 0.39 pg per cell, and synthesized S-35-labeled proteoglycans that included substantial amounts (41-70%) of [S-35]heparin. These findings identify SCF as a single cytokine that can induce immature, IL-3-dependent mast cells to mature and to acquire multiple characteristics of CTMC. These findings also directly demonstrate that SCF can regulate the development of a cellular lineage expressing c-kit through effects on both proliferation and maturation. C1 BETH ISRAEL HOSP,DEPT PATHOL,DIV EXPTL PATHOL,RES E,330 BROOKLINE AVE,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. BETH ISRAEL HOSP,DIV EXPTL PATHOL,BOSTON,MA 02215. NIAID,CLIN INVEST LAB,MAST CELL PHYSIOL SECT,BETHESDA,MD 20892. AMGEN INC,AMGEN CTR,THOUSAND OAKS,CA 91320. FU NCI NIH HHS [CA28834]; NIAID NIH HHS [AI22674, AI23990] NR 42 TC 376 Z9 380 U1 1 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 JUL PY 1991 VL 88 IS 14 BP 6382 EP 6386 DI 10.1073/pnas.88.14.6382 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FW761 UT WOS:A1991FW76100091 PM 1712491 ER PT J AU GERSTEN, DM BIJWAARD, KE WALDEN, TL HEARING, VJ AF GERSTEN, DM BIJWAARD, KE WALDEN, TL HEARING, VJ TI SEROLOGIC DEMONSTRATION OF THE ALBUMINOID NATURE OF THE B700 MURINE MELANOMA ANTIGEN SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID ALPHA-FETOPROTEIN; TUMOR REJECTION; EXPRESSION; SEQUENCE; PROTEINS; PLASMA; ACTIN; CELLS; GENE AB Limited available evidence indicates that the B700 murine melanoma antigen is related to serum albumin, but potential relationships to other members of the serum albumin protein family have not yet been established. Using specific antibodies raised against each of the members of the albumin family, we have studied cross-reactivity by solid phase enzyme-linked immunosorbent assay and Western immunoblotting. We demonstrate that B700 is serologically cross-reactive to members of the serum albumin family, which includes alpha-fetoprotein and vitamin D binding protein. Therefore, B700 is part of the serum albumin family of proteins, although the mechanism underlying its specific expression by transformed melanocytes remains unknown. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. RP GERSTEN, DM (reprint author), GEORGETOWN UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20007, USA. NR 23 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD JUL PY 1991 VL 197 IS 3 BP 310 EP 316 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA FT092 UT WOS:A1991FT09200013 PM 1712493 ER PT J AU SMOLLER, BM AF SMOLLER, BM TI MYOFASCIAL PAIN STATES - RESEARCH, FORENSIC, AND CLINICAL ISSUES SO PSYCHIATRIC ANNALS LA English DT Article ID PRIMARY FIBROMYALGIA SYNDROME; MUSCULOSKELETAL PAIN; FIBROSITIS SYNDROME; SLEEP DISTURBANCE; AMITRIPTYLINE; PREVALENCE C1 GEORGE WASHINGTON UNIV,SCH MED,WASHINGTON,DC 20052. NIH,PAIN STUDIES SECT,BETHESDA,MD 20892. NR 33 TC 2 Z9 2 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD JUL PY 1991 VL 21 IS 7 BP 434 EP 441 PG 8 WC Psychiatry SC Psychiatry GA GB080 UT WOS:A1991GB08000007 ER PT J AU GFROERER, JC HUGHES, AL AF GFROERER, JC HUGHES, AL TI THE FEASIBILITY OF COLLECTING DRUG-ABUSE DATA BY TELEPHONE SO PUBLIC HEALTH REPORTS LA English DT Article AB An evaluation was made of the use of telephone survey methods to collect illicit drug use data. Using data from a national survey that collects data by personal interviews, marijuana and cocaine use prevalence rates among households with telephones and those without were compared in order to assess coverage errors in telephone surveys. Drug use rates were substantially higher among households without telephones, with 24.9 percent of those living in households without telephones reporting use of marijuana in the past year, compared with only 9.4 percent of persons living in households with telephones. Trends in drug use were divergent, with substantial decreases in use occurring between 1985 and 1988 in households with telephones, but not in those without. National prevalence patterns and trends among households with telephones appear to be consistent with national patterns and trends in the total household population, because about 93 percent of the population lives in households with telephones. However, surveys conducted by telephone were found to produce underestimates of illicit drug use prevalence. In a 1988 national telephone survey, estimated rates of past year use were 5.2 percent for marijuana and 1.4 percent for cocaine. Comparable data from a personal visit survey (including only households with telephones and reedited and reweighted to control for differences in data collection protocols) were 8.0 percent for marijuana and 3.1 percent for cocaine use. Comparisons with several other telephone surveys collecting illicit drug use data showed similar results. Based on these results, researchers are advised to use caution in using telephone surveys to produce drug use prevalence estimates. C1 NIDA,STAT ANAL & POPULAT SURV SECT,ROCKVILLE,MD. RP GFROERER, JC (reprint author), NIDA,DIV EPIDEMIOL & PREVENT RES,SURV & ANAL BRANCH,ROCKWALL 2 615,ROCKVILLE,MD 20857, USA. NR 17 TC 47 Z9 47 U1 0 U2 1 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JUL-AUG PY 1991 VL 106 IS 4 BP 384 EP 393 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GB251 UT WOS:A1991GB25100005 PM 1908589 ER PT J AU LANGE, WR BALL, JC ADLER, WH BROWN, E PYLE, R HOFFMAN, W DAX, EM AF LANGE, WR BALL, JC ADLER, WH BROWN, E PYLE, R HOFFMAN, W DAX, EM TI FOLLOW-UP-STUDY OF POSSIBLE HIV SEROPOSITIVITY AMONG ABUSERS OF PARENTERAL DRUGS IN 1971-72 SO PUBLIC HEALTH REPORTS LA English DT Article ID IMMUNE-DEFICIENCY SYNDROME; UNITED-STATES; VIRUS-INFECTION; AIDS; ANTIBODIES; SERUM; RISK AB Serum specimens obtained from a nationwide sample of parenteral drug abusers (PDAs) during the period 1971-72 had previously been screened for human immunodeficiency virus (HIV) antibodies. Some specimens were considered to be positive to both ELISA and Western blot (WB) analysis. These findings have been a topic of controversy, since HIV was not though to have penetrated at-risk populations at such an early date. This study was a followup of those PDAs with apparent seropositivity to WB analysis. Of 10 persons followed, only one death (in 1985) was documented, and postmortem findings were inconsistent with HIV infection. Eight of the remaining PDAs were traced and found to be alive and well in 1989. Fresh specimens were obtained from the two persons with the strongest 1971-72 WB staining and were found to be both ELISA and WB negative on retesting. Their T-cell parameters were within normal limits. We concluded that the earlier WB results were most likely false positives and that definitive evidence of HIV infection in the U.S. addict population as early as 1971-72 is still lacking. C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP LANGE, WR (reprint author), NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224, USA. NR 24 TC 0 Z9 0 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JUL-AUG PY 1991 VL 106 IS 4 BP 451 EP 455 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GB251 UT WOS:A1991GB25100013 PM 1908596 ER PT J AU KONDO, T RIESZ, P AF KONDO, T RIESZ, P TI EFFECT OF ULTRASOUND AND IONIZING-RADIATION ON A STERICALLY HINDERED CYCLIC SECONDARY AMINE - AN ESR STUDY SO RADIATION RESEARCH LA English DT Article ID SPIN-TRAPPING EVIDENCE; ISOTOPE-EXCHANGE-REACTIONS; SINGLET OXYGEN PRODUCTION; AQUEOUS-SOLUTIONS; HYDROXYL RADICALS; THERMAL-DECOMPOSITION; SUPEROXIDE-DISMUTASE; PYROLYSIS RADICALS; WATER MIXTURES; GAMMA-RAYS C1 FUKUI MED SCH,DEPT EXPTL RADIOL & HLTH PHYS,FUKUI 91011,JAPAN. NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NR 43 TC 14 Z9 14 U1 0 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUL PY 1991 VL 127 IS 1 BP 11 EP 18 DI 10.2307/3578082 PG 8 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA FX438 UT WOS:A1991FX43800002 PM 1648754 ER PT J AU SPIRO, IJ MCPHERSON, S COOK, JA LING, CC DEGRAFF, W MITCHELL, JB AF SPIRO, IJ MCPHERSON, S COOK, JA LING, CC DEGRAFF, W MITCHELL, JB TI SENSITIZATION OF LOW-DOSE-RATE IRRADIATION BY NONLETHAL HYPERTHERMIA SO RADIATION RESEARCH LA English DT Note ID DEPENDENCE; REPAIR; DAMAGE; CELLS C1 NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. MEM SLOAN KETTERING CANC CTR,DEPT MED PHYS,NEW YORK,NY 10021. RP SPIRO, IJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. NR 11 TC 22 Z9 22 U1 0 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUL PY 1991 VL 127 IS 1 BP 111 EP 114 DI 10.2307/3578097 PG 4 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA FX438 UT WOS:A1991FX43800017 PM 2068266 ER PT J AU DOUEK, PC LEON, MB GESCHWIND, H COOK, PS SELZER, P MILLER, DL BONNER, RF AF DOUEK, PC LEON, MB GESCHWIND, H COOK, PS SELZER, P MILLER, DL BONNER, RF TI OCCLUSIVE PERIPHERAL VASCULAR-DISEASE - A MULTICENTER TRIAL OF FLUORESCENCE-GUIDED, PULSED DYE LASER-ASSISTED BALLOON ANGIOPLASTY SO RADIOLOGY LA English DT Article DE ARTERIES, FEMORAL; ARTERIES, ILIAC; ARTERIES, LASER ANGIOPLASTY; ARTERIES, POPLITEAL; ARTERIES, STENOSIS OR OBSTRUCTION ID PERCUTANEOUS ANGIOPLASTY; FEMOROPOPLITEAL ARTERY; ATHEROSCLEROTIC PLAQUE; CORONARY ANGIOPLASTY; CLINICAL-EXPERIENCE; RECANALIZATION; ABLATION; GUIDANCE AB Fluorescence-guided, laser-assisted balloon angioplasty was performed in 129 patients with iliac and femoropopliteal artery chronic occlusions (range, 0.5-50.0 cm; mean length, 9.9 cm) after failure of recanalization with standard guide-wire techniques. Laser recanalization and short-term angiographic success were achieved in 101 (72%) and 95 (68%) of 140 occlusions, respectively. Laser and balloon angioplasty failures were encountered in heavily calcified plaques or after perforations and dissections. Complications included perforations (19%), hematomas (5%), thromboses (4%), and distal embolizations (4%). Real-time fluorescence spectroscopy identified thrombus, white fibrous plaque, and media but could not avoid perforations in many cases because laser wire advancement outdistanced fluorescence sensing. Disruption of tissue by means of pressure transients and/or mechanical advancement occurred in at least 36% of lesions where the laser energy was insufficient (< 0.4 J/cm) to ablate significant tissue. Integration of fluorescence guidance with pulsed dye laser ablation is feasible, but additional refinements are necessary to increase safety and efficacy. C1 WASHINGTON HOSP CTR,CARDIOL BRANCH,110 IRVING ST NW,WASHINGTON,DC 20010. NHLBI,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NHLBI,CTR CLIN,BETHESDA,MD 20892. HOP HENRI MONDOR,F-94010 CRETEIL,FRANCE. ST JOSEPH HOSP,DENVER,CO. MERITER HOSP,MADISON,WI. RI Bonner, Robert/C-6783-2015 NR 34 TC 7 Z9 7 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 1991 VL 180 IS 1 BP 127 EP 133 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA FR679 UT WOS:A1991FR67900029 PM 1828901 ER PT J AU HAVERKOS, HW AMSEL, Z DROTMAN, DP AF HAVERKOS, HW AMSEL, Z DROTMAN, DP TI ADVERSE VIRUS-DRUG INTERACTIONS SO REVIEWS OF INFECTIOUS DISEASES LA English DT Review ID PNEUMOCYSTIS-CARINII PNEUMONIA; ACQUIRED IMMUNODEFICIENCY SYNDROME; KAPOSIS SARCOMA; HOMOSEXUAL MEN; REYES-SYNDROME; TRIMETHOPRIM-SULFAMETHOXAZOLE; INFECTIOUS-MONONUCLEOSIS; UNITED-STATES; AIDS; EPIDEMIOLOGY AB Over the last 3 decades, epidemiologists and clinicians have identified a few clinical entities that appear to result when a viral infection and a chemical exposure overlap and interact. Ampicillin rash during infectious mononucleosis, Reye's syndrome following salicylate ingestion and certain viral infections, and the association of AIDS-related Kaposi's sarcoma with abuse of nitrite inhalants and infection due to human immunodeficiency virus are examples of such phenomena. Preclinical research provides additional evidence that viruses and chemicals may interact and produce illnesses in animals. We hypothesize that other virus-drug interactions may exist. Identifying such interactions may lead to a better understanding of the pathogenesis of currently baffling illnesses and may provide insights into ways of preventing and/or treating diseases that appear uncontrollable now. C1 CTR DIS CONTROL, CTR INFECT DIS, DIV HIV AIDS, ATLANTA, GA 30333 USA. RP NIDA, DIV CLIN RES, ROOM 10A-38, 5600 FISHERS LANE, ROCKVILLE, MD 20857 USA. NR 99 TC 38 Z9 40 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0162-0886 J9 REV INFECT DIS PD JUL-AUG PY 1991 VL 13 IS 4 BP 697 EP 704 PG 8 WC Immunology; Microbiology SC Immunology; Microbiology GA GA069 UT WOS:A1991GA06900025 PM 1925290 ER PT J AU FOERSTER, A LEWIS, SW OWEN, MJ MURRAY, RM AF FOERSTER, A LEWIS, SW OWEN, MJ MURRAY, RM TI LOW-BIRTH-WEIGHT AND A FAMILY HISTORY OF SCHIZOPHRENIA PREDICT POOR PREMORBID FUNCTIONING IN PSYCHOSIS SO SCHIZOPHRENIA RESEARCH LA English DT Article DE LOW BIRTH WEIGHT; OBSTETRIC COMPLICATION; FAMILY HISTORY OF SCHIZOPHRENIA; POOR PREMORBID FUNCTIONING; PRESCHIZOPHRENIC CHILD ID SCHIZOAFFECTIVE DISORDER; OBSTETRIC COMPLICATIONS; RISK; RELIABILITY; ADJUSTMENT; DIAGNOSIS; SPECTRUM; ILLNESS; GENDER AB Risk factors thought to predispose to schizophrenia, and premorbid functioning, were assessed blind to diagnosis by interviewing the mothers of 73 patients with DSM-III schizophrenia or affective psychosis. Higher risk of schizophrenia in relatives, lower mean birth weight, a more frequent history of obstetric complications, and poorer educational achievement distinguished the patients with schizophrenia from those with affective psychosis. Low birth weight and obstetric complications each predicted childhood schizoid and schizotypal traits. Poor social adjustment between ages 5 and 11 was predicted by low birthweight and by a family history of schizophrenia. C1 KINGS COLL HOSP,DE CRESPIGNY PK,LONDON SE5 8AF,ENGLAND. NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. CHARING CROSS HOSP,DEPT PSYCHIAT,LONDON W6 8RF,ENGLAND. UNIV COLL CARDIFF,DEPT PSYCHOL MED,CARDIFF CF4 4XN,S GLAM,WALES. INST PSYCHIAT,LONDON SE5 8AF,ENGLAND. RI turton, miranda/F-4682-2011; Murray, Robin/F-8658-2012; OI Murray, Robin/0000-0003-0829-0519; Lewis, Shon/0000-0003-1861-4652 NR 52 TC 71 Z9 72 U1 0 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 JUL-AUG PY 1991 VL 5 IS 1 BP 13 EP 20 DI 10.1016/0920-9964(91)90049-W PG 8 WC Psychiatry SC Psychiatry GA FP597 UT WOS:A1991FP59700002 PM 1854675 ER PT J AU SULLIVAN, KM REID, CD AF SULLIVAN, KM REID, CD TI INTRODUCTION TO A SYMPOSIUM ON SICKLE-CELL-ANEMIA - CURRENT RESULTS OF COMPREHENSIVE CARE AND THE EVOLVING ROLE OF BONE-MARROW TRANSPLANTATION SO SEMINARS IN HEMATOLOGY LA English DT Editorial Material ID DISEASE; CHILDREN; PROPHYLAXIS; THALASSEMIA; MORTALITY; GRAFT C1 UNIV WASHINGTON,SCH MED,SEATTLE,WA 98195. NHLBI,SICKLE CELL DIS BRANCH,BETHESDA,MD 20892. RP SULLIVAN, KM (reprint author), FRED HUTCHINSON CANC RES CTR,DIV ENGN SCI,1124 COLUMBIA ST,SEATTLE,WA 98104, USA. FU NHLBI NIH HHS [HL36444] NR 24 TC 17 Z9 17 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JUL PY 1991 VL 28 IS 3 BP 177 EP 179 PG 3 WC Hematology SC Hematology GA FV568 UT WOS:A1991FV56800001 PM 1887244 ER PT J AU BONOW, RO DILSIZIAN, V AF BONOW, RO DILSIZIAN, V TI THALLIUM 201 FOR ASSESSMENT OF MYOCARDIAL VIABILITY SO SEMINARS IN NUCLEAR MEDICINE LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; CORONARY-BYPASS SURGERY; WALL-MOTION; METABOLIC-ACTIVITY; TL-201 REINJECTION; F-18 DEOXYGLUCOSE; VIABLE MYOCARDIUM; ARTERY DISEASE; N-13 AMMONIA; BLOOD-FLOW RP BONOW, RO (reprint author), NHLBI,CARDIOL BRANCH,BLDG 10,ROOM 7B-15,BETHESDA,MD 20892, USA. NR 47 TC 50 Z9 52 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0001-2998 J9 SEMIN NUCL MED JI Semin. Nucl. Med. PD JUL PY 1991 VL 21 IS 3 BP 230 EP 241 DI 10.1016/S0001-2998(05)80043-1 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA FW343 UT WOS:A1991FW34300008 PM 1948113 ER PT J AU HORN, JE MCQUILLAN, GM SHAH, KV GUPTA, P DANIEL, RW RAY, PA QUINN, TC HOOK, EW AF HORN, JE MCQUILLAN, GM SHAH, KV GUPTA, P DANIEL, RW RAY, PA QUINN, TC HOOK, EW TI GENITAL HUMAN PAPILLOMAVIRUS INFECTIONS IN PATIENTS ATTENDING AN INNER-CITY STD CLINIC SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID DIAGNOSIS; WOMEN; HYBRIDIZATION; EPIDEMIOLOGY; PREVALENCE; CONDYLOMA; CYTOLOGY AB One hundred and sixteen consecutive women attending a Baltimore City STD clinic were studied for the prevalence of human papillomavirus (HPV) infection of the genital tract using three criteria: presence of clinically recognized (visible) genital warts, cytopathologic evidence suggestive of HPV infection in a Papanicolaou smear, and analysis of cervical scrapes for genital tract HPV genomic sequences by Southern hybridization. The women were young (median age: 22 years) and more than 80% had a history of one or more STDs. The prevalences were 17% for visible warts, 41 % for cytologic findings suggestive HPV infection, and 12% for HPV DNA in cervical scrapes. Comparing the results of the three techniques, HPV DNA was found significantly more often in cytopathology-positive women than in cytopathology-negative women (18% vs. 5%, P = 0.05) and in women with visible warts than in women without visible warts (29% vs. 6%, P = 0.01). Visible warts were more common in women with HPV-DNA-positive cervical scrapes than in HPV-negative women (50% vs. 14%, P =.01). Although 52% of women were judged as infected by at least one of the three criteria, only 4% were infected by using all three criteria. The prevalence of infection was 23% if cytopathology alone was excluded as evidence of HPV infection. These results indicate the difficulty in an accurate estimation of the prevalence of HPV infections, even in a high-risk population. C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD 21218. BALTIMORE CITY DEPT HLTH,BALTIMORE,MD. CTR DIS CONTROL,NATL CTR HLTH STAT,HYATTSVILLE,MD. UNIV PENN,MED CTR,PHILADELPHIA,PA 19104. NIAID,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-16959] NR 21 TC 8 Z9 8 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD JUL-SEP PY 1991 VL 18 IS 3 BP 183 EP 187 DI 10.1097/00007435-199107000-00012 PG 5 WC Infectious Diseases SC Infectious Diseases GA GB752 UT WOS:A1991GB75200012 PM 1658954 ER PT J AU SHAPIRO, M KOZAK, CA AF SHAPIRO, M KOZAK, CA TI GENETIC-MAPPING IN THE MOUSE OF 4 LOCI RELATED TO THE JUN FAMILY OF TRANSCRIPTIONAL ACTIVATORS SO SOMATIC CELL AND MOLECULAR GENETICS LA English DT Article ID PROTO-ONCOGENE FAMILY; C-JUN; CHROMOSOMAL LOCALIZATION; GROWTH-FACTORS; FACTOR AP-1; FOS; DNA; PROTOONCOGENE; LINKAGE; SEQUENCES AB Southern blot analysis of DNAs from somatic cell hybrids and the progeny of an intersubspecies backcross were used to identify and chromosomally map four loci in the mouse containing sequences cross-reactive to members of the jun family of transcriptional activators. The murine homolog of v-jun, Jun, was mapped to chromosome (Chr) 4, and a locus containing jun B-related sequences (Junb) was mapped to Chr 8. Probes for jun D identified two genetic loci; one, Jund-1, is near Junb on Chr 8, and a second, previously unidentified locus termed Jund-2, was mapped to Chr 2. C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. RP SHAPIRO, M (reprint author), NIAID,IMMUNOPATHOL LAB,BETHESDA,MD 20892, USA. NR 32 TC 10 Z9 10 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0740-7750 J9 SOMAT CELL MOLEC GEN JI Somat.Cell Mol.Genet. PD JUL PY 1991 VL 17 IS 4 BP 341 EP 347 DI 10.1007/BF01233059 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA GE701 UT WOS:A1991GE70100002 PM 1887331 ER PT J AU CALDECOTTHAZARD, S GUZE, BH KLING, MA KLING, A BAXTER, LR AF CALDECOTTHAZARD, S GUZE, BH KLING, MA KLING, A BAXTER, LR TI CLINICAL AND BIOCHEMICAL ASPECTS OF DEPRESSIVE-DISORDERS .1. INTRODUCTION, CLASSIFICATION, AND RESEARCH TECHNIQUES SO SYNAPSE LA English DT Review DE DEPRESSIVE DISORDERS; HUMANS; ANIMAL MODELS ID POSITRON EMISSION TOMOGRAPHY; OBSESSIVE-COMPULSIVE DISORDER; CEREBRAL GLUCOSE-METABOLISM; DEXAMETHASONE SUPPRESSION TEST; BIPOLAR AFFECTIVE-DISORDERS; TRICYCLIC ANTI-DEPRESSANTS; BETA-ADRENERGIC RECEPTORS; UNCONTROLLABLE STRESS; CHRONIC-SCHIZOPHRENIA; LEARNED HELPLESSNESS AB The present review focuses on recent data from clinical and animal research concerning the biochemical bases of depressive disorders, diagnosis, and treatment. In addition to integrating these data, problems and future directions in this research are discussed. The review is presented in three parts. This study, Part I, describes diagnostic classification schemes for depressive disorders, some epidemiological and biological correlates of the classifications, and research techniques for investigating depressive disorders. Research techniques include animal models, human biochemical techniques, and Positron Emission Tomography. In a future issue, Part II will discuss various transmitter/receptor theories of depressive disorders, e.g., noradrenergic, serotonergic, cholinergic, and dopaminergic, GABAergic, and peptidergic theories. Also in a future issue, Part III will discuss treatments for depression and some of the controversies in the field. C1 UNIV CALIF LOS ANGELES,BIOMED & ENVIRONM SCI LAB,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT,LOS ANGELES,CA 90024. VET ADM MED CTR,DEPT PSYCHIAT,SEPULVEDA,CA 91343. NIMH,DIV INTRAMURAL RES PROGRAMS,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. RI Kling, Mitchel/F-4152-2010 OI Kling, Mitchel/0000-0002-2232-1409 NR 209 TC 21 Z9 21 U1 2 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD JUL PY 1991 VL 8 IS 3 BP 185 EP 211 DI 10.1002/syn.890080306 PG 27 WC Neurosciences SC Neurosciences & Neurology GA FR906 UT WOS:A1991FR90600005 PM 1948669 ER PT J AU READ, EJ CARDINE, LL YU, MY AF READ, EJ CARDINE, LL YU, MY TI FLOW CYTOMETRIC DETECTION OF HUMAN RED-CELLS LABELED WITH A FLUORESCENT MEMBRANE LABEL - POTENTIAL APPLICATION TO INVIVO SURVIVAL STUDIES SO TRANSFUSION LA English DT Article ID IN-111 AB In vivo survival studies of human red cells (RBCs) are commonly carried out by using chromium-51 (Cr-51), a gamma-emitting radionuclide, as the cell label. The effects of labeling human RBCs with PKH-2, a nonradioactive lipophilic fluorescent dye that binds to the cell membrane, and the feasibility of detecting the labeled cells by flow cytometric analysis were investigated. Optimal labeling, defined as maximum mean fluorescence intensity with minimal cell-to-cell variability in fluorescence intensity and minimal cell loss, was achieved with the use of 15.0 x 10(-6) M (15.0 x 10(-6) mol/L) PKH-2 and a cell concentration of 4.0 x 10(9) RBCs per mL. Both freshly drawn and stored RBCs could be labeled, but RBCs stored for more than 20 days did not take up the label as uniformly as fresher cells. Although labeling with PKH-2 did not interfere with the detection of ABO, Rh(D), or common minor RBC antigens by routine serologic methods, it resulted in a morphologic appearance resembling echinocytosis and an increased resistance to osmotic lysis by hypotonic saline. RBCs labeled by this method could be quantitated accurately in blood samples in which their proportion was 0.01 percent, or 1 labeled cell in 10,000 cells. This method holds promise as a simple, reliable, and sensitive method for the detection of labeled human RBCs, but the in vivo significance of the label's effects on cell morphology and osmotic fragility is not known. Further studies directly comparing PKH-2-labeled and Cr-51-labeled RBCs will be necessary to establish the accuracy of the former method in determining the in vivo survival of human RBCs. RP READ, EJ (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,SPECIAL SERV LAB,BETHESDA,MD 20892, USA. NR 16 TC 13 Z9 13 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUL-AUG PY 1991 VL 31 IS 6 BP 502 EP 508 DI 10.1046/j.1537-2995.1991.31691306246.x PG 7 WC Hematology SC Hematology GA FY567 UT WOS:A1991FY56700007 PM 1853443 ER PT J AU COOPER, MM CLARK, RE WALDMANN, TA AF COOPER, MM CLARK, RE WALDMANN, TA TI SURVIVAL OF CARDIAC XENOGRAFTS IN RHESUS-MONKEYS - REPLY SO TRANSPLANTATION LA English DT Letter ID TRANSPLANTATION C1 ALLEGHENY GEN HOSP,CARDIOVASC & PULM RES CTR,PITTSBURGH,PA 15212. NCI,METAB BRANCH,BETHESDA,MD 20892. RP COOPER, MM (reprint author), COLUMBIA UNIV COLL PHYS & SURG,DEPT SURG,NEW YORK,NY 10032, USA. NR 3 TC 0 Z9 0 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 JUL PY 1991 VL 52 IS 1 BP 181 EP 182 DI 10.1097/00007890-199107000-00045 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA FX180 UT WOS:A1991FX18000045 ER PT J AU LEROITH, D ADAMO, M WERNER, H ROBERTS, CT AF LEROITH, D ADAMO, M WERNER, H ROBERTS, CT TI INSULIN-LIKE GROWTH-FACTORS AND THEIR RECEPTORS AS GROWTH-REGULATORS IN NORMAL PHYSIOLOGY AND PATHOLOGICAL STATES SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID I GENE-EXPRESSION; MESSENGER RIBONUCLEIC-ACID; HUMAN-BREAST CANCER; IGF BINDING-PROTEIN; HORMONAL-REGULATION; RAT; RNA; HYPOGLYCEMIA; SOMATOMEDIN; TRANSCRIPTS AB Insulinlike growth factors (IGFs), their binding proteins, and receptors are expressed by many different tissues, suggesting that they may act as parts of an autocrine-paracrine system in addition to having a classic endocrine role. Since these growth factors are essential for the normal growth and development of the organism, their altered rate of production in a number of important disease states results in severe growth alterations. These include nutritional deprivation, growth hormone deficiency, diabetes, and malignancy. RP LEROITH, D (reprint author), NIDDK,DIABET BRANCH,BETHESDA,MD 20892, USA. NR 41 TC 111 Z9 111 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD JUL-AUG PY 1991 VL 2 IS 4 BP 134 EP 139 DI 10.1016/1043-2760(91)90003-6 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FY949 UT WOS:A1991FY94900003 ER PT J AU USALA, SJ WEINTRAUB, BD AF USALA, SJ WEINTRAUB, BD TI THYROID-HORMONE RESISTANCE SYNDROMES SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID GENERALIZED RESISTANCE; RECEPTOR; BINDING; GENE; BETA; TRIIODOTHYRONINE; HYPERTHYROIDISM; SECRETION; KINDREDS; MUTATION AB The gene for generalized thyroid hormone resistance has been mapped to the c-erbA-beta thyroid hormone receptor on chromosome 3 in multiple kindreds. Different mutations have been identified in the triiodothyronine (T3)-binding domain of c-erbA-beta and result in variable changes in T3-binding affinity. The variant phenotypes of thyroid hormone resistance are likely due to different mutations in the c-erbA-beta receptor. C1 NIH,MOLEC CELLULAR & NUTR ENDOCRINOL BRANCH,BETHESDA,MD 20892. RP USALA, SJ (reprint author), E CAROLINA UNIV,SCH MED,DEPT MED,GREENVILLE,NC 27858, USA. NR 26 TC 26 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD JUL-AUG PY 1991 VL 2 IS 4 BP 140 EP 144 DI 10.1016/1043-2760(91)90004-7 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FY949 UT WOS:A1991FY94900004 ER PT J AU KUHAR, MJ RITZ, MC BOJA, JW AF KUHAR, MJ RITZ, MC BOJA, JW TI THE DOPAMINE HYPOTHESIS OF THE REINFORCING PROPERTIES OF COCAINE SO TRENDS IN NEUROSCIENCES LA English DT Article ID FREELY MOVING RATS; NUCLEUS ACCUMBENS; EXTRACELLULAR DOPAMINE; INVIVO MICRODIALYSIS; PREFERENTIALLY INCREASE; BRAIN-STIMULATION; MESOLIMBIC SYSTEM; RHESUS-MONKEYS; AMPHETAMINE; RECEPTOR AB A variety of evidence suggests a 'dopamine hypothesis' for the reinforcing properties of cocaine. This hypothesis proposes that cocaine binds at the dopamine transporter and mainly inhibits neurotransmitter re-uptake; the resulting potentiation of dopaminergic neurotransmission in mesolimbocortical pathways ultimately causes reinforcement. This model suggests potential medications for treatment of cocaine abuse and dependence. Some, but not all, pharmacological data in humans support the hypothesis and additional experimentation is needed. C1 NIDA,ADDICT RES CTR,PHARMACOL BRANCH,BALTIMORE,MD 21224. RP KUHAR, MJ (reprint author), NIDA,ADDICT RES CTR,NEUROSCI BRANCH,BALTIMORE,MD 21224, USA. NR 60 TC 859 Z9 864 U1 2 U2 42 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD JUL PY 1991 VL 14 IS 7 BP 299 EP 302 DI 10.1016/0166-2236(91)90141-G PG 4 WC Neurosciences SC Neurosciences & Neurology GA FU063 UT WOS:A1991FU06300009 PM 1719677 ER PT J AU ROSSIER, MF PUTNEY, JW AF ROSSIER, MF PUTNEY, JW TI THE IDENTITY OF THE CALCIUM-STORING, INOSITOL 1,4,5-TRISPHOSPHATE-SENSITIVE ORGANELLE IN NONMUSCLE CELLS - CALCIOSOME, ENDOPLASMIC-RETICULUM ... OR BOTH SO TRENDS IN NEUROSCIENCES LA English DT Article ID PANCREATIC ACINAR-CELLS; SARCOPLASMIC-RETICULUM; PLASMA-MEMBRANE; INTRACELLULAR CALCIUM; HUMAN-NEUTROPHILS; BINDING PROTEIN; RAT INSULINOMA; CA-2+ RELEASE; HL-60 CELLS; RECEPTOR AB Although the initial phase of receptor-mediated Ca2+ signaling, involving Ca2+ release from intracellular stores by inositol 1,4,5-trisphosphate, is relatively well characterized, the nature of the organelle releasing Ca2+ is a controversial subject. At issue is the question of whether Ca2+ is released from the endoplasmic reticulum, or from a more specialized organelle called the 'calciosome'. In this review, we attempt to analyse the arguments for and against these two views, and attempt to reconcile some of the apparently conflicting findings by proposing a hypothetical model of the inositol 1,4,5-trisphosphate-sensitive Ca2+ pool. RP ROSSIER, MF (reprint author), NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709, USA. NR 51 TC 83 Z9 83 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD JUL PY 1991 VL 14 IS 7 BP 310 EP 314 DI 10.1016/0166-2236(91)90143-I PG 5 WC Neurosciences SC Neurosciences & Neurology GA FU063 UT WOS:A1991FU06300011 PM 1719679 ER PT J AU ARRIGHI, HM METTER, EJ GUESS, HA FOZZARD, JL AF ARRIGHI, HM METTER, EJ GUESS, HA FOZZARD, JL TI NATURAL-HISTORY OF BENIGN PROSTATIC HYPERPLASIA AND RISK OF PROSTATECTOMY - THE BALTIMORE LONGITUDINAL-STUDY OF AGING SO UROLOGY LA English DT Article; Proceedings Paper CT SYMP AT THE 47TH ANNUAL MEETING OF THE AMERICAN GERIATRICS SOC / 11TH ANNUAL MEETING OF THE AMERICAN FEDERATION FOR AGING RESEARCH : BENIGN PROSTATIC HYPERPLASIA CY MAY 18, 1990 CL ATLANTA, GA SP AMER GERIATR SOC, AMER FEDERAT AGING RES ID SYMPTOMS AB The natural history of prostatism (clinically diagnosed benign prostatic hyperplasia) is examined based on symptom questionnaires and digital rectal examinations administered periodically to 1,057 men followed prospectively for up to thirty years in the Baltimore Longitudinal Study of Aging (BLSA). Benign prostatic hyperplasia (BPH) was clinically diagnosed in 527 men, 110 had a prostatectomy for BPH, and in 21 prostate cancer developed. Among men aged sixty or older with prostatic enlargement and obstructive symptoms, the twenty-year probability of surgery was 39 percent; for men aged fifty to fifty-nine years this probability was 24 percent; and for men aged forty to forty-nine years, the probability was 13 percent. The age-specific prevalence of clinically diagnosed BPH agreed closely at all ages with the age-specific autopsy prevalence of pathologically defined BPH from a published international compilation of 5 independent autopsy studies involving 1,075 prostates. C1 UNIV N CAROLINA,SCH PUBL HLTH,DEPT EPIDEMIOL,CB-7400,CHAPEL HILL,NC 27599. MERCK SHARP & DOHME LTD,W POINT,PA 19486. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 20 TC 88 Z9 89 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD JUL PY 1991 VL 38 IS 1 SU S BP 4 EP 8 DI 10.1016/0090-4295(91)80191-9 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA FX094 UT WOS:A1991FX09400002 PM 1714657 ER PT J AU TREANOR, JJ TIERNEY, EL LONDON, WT MURPHY, BR AF TREANOR, JJ TIERNEY, EL LONDON, WT MURPHY, BR TI CHARACTERIZATION OF THE ATTENUATING M-GENE AND NP-GENE SEGMENTS OF THE AVIAN INFLUENZA-A MALLARD-78 VIRUS DURING INVITRO PRODUCTION OF AVIAN-HUMAN REASSORTANT VACCINE VIRUSES AND AFTER REPLICATION IN HUMANS AND PRIMATES SO VACCINE LA English DT Article DE INFLUENZA-A VIRUS; LIVE VIRUS VACCINES; MATRIX PROTEINS; NUCLEOPROTEINS; GENETIC REASSORTMENT; INFLUENZA VACCINES ID TEMPERATURE-SENSITIVE PHENOTYPE; NUCLEOTIDE-SEQUENCE ANALYSIS; HOST RANGE RESTRICTION; ADULT VOLUNTEERS; NUCLEOPROTEIN GENE; SQUIRREL-MONKEYS; POLYMERASE GENES; LIVE; H3N2; STRAIN AB A unique requirement for live attenuated reassortant influenza vaccines is the need to generate new reassortant vaccine viruses with the appearance of each new antigenic variant. Thus, the attenuation phenotype conferred by the attenuated donor influenza virus must remain genetically stable during the generation of each new reassortant vaccine virus. In this study we used nucleotide sequence analysis to evaluate the genetic stability of the attenuating M and NP genes of the avian influenza A/Mallard/NY/6750/78 attenuated donor virus during the in vitro generation and subsequent in vivo replication of avian-human (AH) influenza A reassortant vaccine viruses in monkeys and humans. Nucleotide sequence changes in the M and NP genes occurred at a rate of almost-equal-to 0.61 substitutions/1000 nt/reassortant during in vitro generation of four AH reassortant viruses. Only two nucleotide sequence changes occurred in the M and NP gene segments of four isolates of H1N1 or H3N2 AH vaccine viruses following 6-8 days of replication in seronegative children, and neither change affected amino acids previously identified as playing a potential role in attenuation. In addition, there were no changes in the nucleotide sequence of the M and NP genes of single gene AH reassortant viruses following five serial passages in squirrel monkeys. Finally, there was no change in the level or duration of replication of the single gene reassortant viruses in the upper or lower respiratory tract of monkeys following serial passage. These results suggest that nucleotide sequence changes occur infrequently during the production of reassortant influenza A vaccine viruses and their subsequent replication in humans and monkeys, and that genetic instability does not appear to represent a significant obstacle to this approach for production of live attenuated vaccines. C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. NICDS,BETHESDA,MD. NR 24 TC 4 Z9 6 U1 0 U2 1 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD JUL PY 1991 VL 9 IS 7 BP 495 EP 501 DI 10.1016/0264-410X(91)90035-5 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA FV684 UT WOS:A1991FV68400007 PM 1897305 ER PT J AU NEBREDA, AR BRYAN, T SEGADE, F WINGFIELD, P VENKATESAN, S SANTOS, E AF NEBREDA, AR BRYAN, T SEGADE, F WINGFIELD, P VENKATESAN, S SANTOS, E TI BIOCHEMICAL AND BIOLOGICAL COMPARISON OF HIV-1 NEF AND RAS GENE-PRODUCTS SO VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; GTP-BINDING; HTLV-III; SIGNAL TRANSDUCTION; MUTATIONAL ANALYSIS; ONCOGENE PRODUCT; ESCHERICHIA-COLI; PROTEIN; P21; REPLICATION C1 NIAID,MOLEC MICROBIOL LAB,BG 4,RM 312,BETHESDA,MD 20892. NIH,PROT EXPRESS LAB,BETHESDA,MD 20892. NR 38 TC 46 Z9 46 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 JUL PY 1991 VL 183 IS 1 BP 151 EP 159 DI 10.1016/0042-6822(91)90128-X PG 9 WC Virology SC Virology GA FQ368 UT WOS:A1991FQ36800017 PM 2053279 ER PT J AU AGY, MB FOY, K GALE, MJ BENVENISTE, RE CLARK, EA KATZE, MG AF AGY, MB FOY, K GALE, MJ BENVENISTE, RE CLARK, EA KATZE, MG TI VIRAL AND CELLULAR GENE-EXPRESSION IN CD4+ HUMAN LYMPHOID-CELL LINES INFECTED BY THE SIMIAN IMMUNODEFICIENCY VIRUS, SIV/MNE SO VIROLOGY LA English DT Article ID AFRICAN-GREEN MONKEYS; T-LYMPHOTROPIC RETROVIRUS; EPSTEIN-BARR VIRUS; B-CELLS; RHESUS-MONKEYS; HTLV-III/LAV; TYPE-1 VPU; ACTIVATION; MACAQUES; LENTIVIRUS C1 UNIV WASHINGTON,SCH MED SC-42,DEPT MICROBIOL,SEATTLE,WA 98195. UNIV WASHINGTON,REG PRIMATE RES CTR,SEATTLE,WA 98195. NCI,FREDERICK CANC RES CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. RI Clark, Edward/K-3462-2012; OI Gale, Michael/0000-0002-6332-7436 FU NCRR NIH HHS [RR 00166]; NIAID NIH HHS [AI 22646, AI 26503] NR 52 TC 17 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JUL PY 1991 VL 183 IS 1 BP 170 EP 180 DI 10.1016/0042-6822(91)90130-4 PG 11 WC Virology SC Virology GA FQ368 UT WOS:A1991FQ36800019 PM 1675822 ER PT J AU STEC, DS HILL, MG COLLINS, PL AF STEC, DS HILL, MG COLLINS, PL TI SEQUENCE-ANALYSIS OF THE POLYMERASE L-GENE OF HUMAN RESPIRATORY SYNCYTIAL VIRUS AND PREDICTED PHYLOGENY OF NONSEGMENTED NEGATIVE-STRAND VIRUSES SO VIROLOGY LA English DT Article ID VESICULAR STOMATITIS-VIRUS; NEWCASTLE-DISEASE VIRUS; AMINO-ACID-SEQUENCES; L-PROTEIN; NUCLEOTIDE-SEQUENCE; RNA-POLYMERASE; SIMILARITY SEARCHES; CONSERVED DOMAINS; IDENTIFICATION; SENDAI C1 NIAID, INFECT DIS LAB, BLDG 7 ROOM 100, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 42 TC 87 Z9 89 U1 1 U2 16 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUL PY 1991 VL 183 IS 1 BP 273 EP 287 DI 10.1016/0042-6822(91)90140-7 PG 15 WC Virology SC Virology GA FQ368 UT WOS:A1991FQ36800029 PM 2053282 ER PT J AU RUSCETTI, FW JACOBSEN, SE BIRCHENALLROBERTS, M BROXMEYER, HE ENGELMANN, GL DUBOIS, C KELLER, JR AF RUSCETTI, FW JACOBSEN, SE BIRCHENALLROBERTS, M BROXMEYER, HE ENGELMANN, GL DUBOIS, C KELLER, JR TI ROLE OF TRANSFORMING GROWTH FACTOR-BETA-1 IN REGULATION OF HEMATOPOIESIS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID COLONY-FORMING CELLS; FACTOR-BETA; BONE-MARROW; TGF-BETA; PROGENITOR CELLS; GENE-EXPRESSION; STEM-CELLS; 2 FORMS; PROLIFERATION; INHIBITION C1 DYNCORP,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS DEV PROGRAM,FREDERICK,MD 21702. INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,INDIANAPOLIS,IN 46202. LOYOLA UNIV,STRITCH SCH MED,DEPT MED,MAYWOOD,IL 60153. RP RUSCETTI, FW (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 43 TC 33 Z9 34 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD JUN 30 PY 1991 VL 628 BP 31 EP 43 DI 10.1111/j.1749-6632.1991.tb17220.x PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FZ456 UT WOS:A1991FZ45600004 PM 2069310 ER PT J AU KEHRL, JH TAYLOR, A KIM, SJ FAUCI, AS AF KEHRL, JH TAYLOR, A KIM, SJ FAUCI, AS TI TRANSFORMING GROWTH-FACTOR-BETA IS A POTENT NEGATIVE REGULATOR OF HUMAN-LYMPHOCYTES SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID T-CELL LEUKEMIA; HUMAN-PLATELETS; RETINOBLASTOMA PROTEIN; SUPPRESSOR FACTOR; GENE; PURIFICATION; VIRUS; RESPONSIVENESS; EXPRESSION; INHIBITION C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. RP KEHRL, JH (reprint author), NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892, USA. OI Kehrl, John/0000-0002-6526-159X NR 42 TC 40 Z9 41 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD JUN 30 PY 1991 VL 628 BP 345 EP 353 DI 10.1111/j.1749-6632.1991.tb17267.x PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FZ456 UT WOS:A1991FZ45600046 PM 1648884 ER PT J AU OH, I CHI, SC VISHNUVAJJALA, BR ANDERSON, BD AF OH, I CHI, SC VISHNUVAJJALA, BR ANDERSON, BD TI STABILITY AND SOLUBILIZATION OF OXATHIIN CARBOXANILIDE, A NOVEL ANTI-HIV AGENT SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE OXATHIIN DEGRADATION; ESTER; HYDROLYSIS; SOLUBILIZATION; EMULSION FORMULATION; AIDS; COSOLVENT; HYDROXYPROPYL-BETA-CYCLODEXTRIN ID EMULSION; CYCLODEXTRINS; POLAR; DRUGS AB Oxathiin carboxanilide (benzoic acid, 2-chloro-5-[[5,6-dihydro-2-methyl-1,4-oxathiin-3-yl)carbonyl]amino]isopropyl ester (NSC 615985; I) is a novel inhibitor of HIV which is currently undergoing preclinical evaluation as an anti-AIDS agent. The purpose of this study was to generate preliminary information on the stability, degradation products, and solubility of oxathiin carboxanilide in order to develop prototype parenteral dosage forms to be used in the early stages of preclinical and clinical evaluation of this candidate. A stability-indicating HPLC assay was developed for use in monitoring drug solubility and stability. The rate of degradation of I was determined in aqueous buffers as a function of pH and temperature. An analysis of the pH-rate profile indicates that oxathiin carboxanilide undergoes specific acid and specific base catalyzed hydrolysis in addition to a pH-independent reaction between pH 5 and 7. The maximum shelf-life of I in aqueous solution is almost-equal-to 16 days at 25-degrees-C. In acid, the primary route of decomposition of I involves water addition to the oxathiin ring and subsequent ring-opening. In alkaline solution, ester hydrolysis predominates. The water solubility of I was found to be extremely low (1.3-mu-g/ml) necessitating a search for cosolvent systems or complexing agents which would provide solubilities > 5 mg/ml for toxicological studies. The desired solubility was achieved in 70% dimethylacetamide/water and 70-80% dimethylsulfoxide/water cosolvents. A more physiologically compatible extemporaneous lipid emulsion was also prepared containing 0.75 mg/ml of I in Liposyn II 20%. The stability of I in the 20% lipid emulsion was established over a period of 48 h at 25-degrees-C. C1 UNIV UTAH,DEPT PHARMACEUT,SALT LAKE CITY,UT 84108. NCI,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NR 18 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARM JI Int. J. Pharm. PD JUN 30 PY 1991 VL 73 IS 1 BP 23 EP 31 DI 10.1016/0378-5173(91)90096-7 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FX547 UT WOS:A1991FX54700004 ER PT J AU HELM, BA PADLAN, EA AF HELM, BA PADLAN, EA TI COMMERCE VERSUS COLLABORATION SO LANCET LA English DT Letter ID SITE C1 NIDDK,BETHESDA,MD. RP HELM, BA (reprint author), UNIV SHEFFIELD,KREBS INST BIOMOLEC RES,SHEFFIELD S10 2UH,ENGLAND. NR 3 TC 0 Z9 0 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 JUN 29 PY 1991 VL 337 IS 8757 BP 1608 EP 1608 DI 10.1016/0140-6736(91)93304-R PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA FU551 UT WOS:A1991FU55100050 PM 1675734 ER PT J AU WEIGHT, FF LOVINGER, DM WHITE, G PEOPLES, RW AF WEIGHT, FF LOVINGER, DM WHITE, G PEOPLES, RW TI ALCOHOL AND ANESTHETIC ACTIONS ON EXCITATORY AMINO ACID-ACTIVATED ION CHANNELS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID LONG-TERM POTENTIATION; D-ASPARTATE RECEPTORS; HIPPOCAMPAL-NEURONS; SYNAPTIC TRANSMISSION; PYRAMIDAL CELLS; NMDA RECEPTORS; ETHANOL; RAT; INHIBITION; SLICE RP WEIGHT, FF (reprint author), NATL INST ALCOHOL ABUSE & ALCOHOLISM,ELECTROPHYSIOL SECT,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 40 TC 55 Z9 55 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD JUN 28 PY 1991 VL 625 BP 97 EP 107 DI 10.1111/j.1749-6632.1991.tb33833.x PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FZ455 UT WOS:A1991FZ45500009 PM 1711821 ER PT J AU TABAKOFF, B RABE, CS HOFFMAN, PL AF TABAKOFF, B RABE, CS HOFFMAN, PL TI SELECTIVE EFFECTS OF SEDATIVE HYPNOTIC DRUGS ON EXCITATORY AMINO-ACID RECEPTORS IN BRAIN SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID D-ASPARTATE RECEPTOR; ETHANOL WITHDRAWAL SEIZURES; GAMMA-AMINOBUTYRIC ACID; RAT-BRAIN; HIPPOCAMPAL-NEURONS; GLUTAMATE RECEPTOR; CHANNEL COMPLEX; NMDA-RECEPTORS; GLYCINE; ALCOHOL C1 NIAAA, DIV INTRAMURAL CLIN & BIOL RES, ROCKVILLE, MD 20852 USA. NR 47 TC 12 Z9 12 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD JUN 28 PY 1991 VL 625 BP 488 EP 495 DI 10.1111/j.1749-6632.1991.tb33879.x PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FZ455 UT WOS:A1991FZ45500055 PM 1647738 ER PT J AU MORROW, AL MONTPIED, P PAUL, SM AF MORROW, AL MONTPIED, P PAUL, SM TI GABA-A RECEPTOR FUNCTION AND EXPRESSION FOLLOWING CHRONIC ETHANOL AND BARBITURATE ADMINISTRATION SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID GAMMA-AMINOBUTYRIC ACID; ALPHA-SUBUNIT; RAT-BRAIN; REGIONAL EXPRESSION; CHLORIDE CHANNELS; MESSENGER-RNA; A RECEPTOR; BENZODIAZEPINE; BINDING; NEURONS C1 NIMH,CLIN NEUROSCI BRANCH,MOLEC PHARMACOL SECT,BETHESDA,MD 20892. NR 49 TC 11 Z9 11 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD JUN 28 PY 1991 VL 625 BP 496 EP 507 DI 10.1111/j.1749-6632.1991.tb33880.x PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FZ455 UT WOS:A1991FZ45500056 PM 1711815 ER PT J AU NASH, HA CAMPBELL, DB KRISHNAN, KS AF NASH, HA CAMPBELL, DB KRISHNAN, KS TI NEW MUTANTS OF DROSOPHILA THAT ARE RESISTANT TO THE ANESTHETIC EFFECTS OF HALOTHANE SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID CAENORHABDITIS-ELEGANS; SENSITIVITY RP NASH, HA (reprint author), NIMH,MOLEC BIOL LAB,BLDG 36,ROOM 1B-08,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 12 TC 16 Z9 17 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD JUN 28 PY 1991 VL 625 BP 540 EP 544 DI 10.1111/j.1749-6632.1991.tb33885.x PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FZ455 UT WOS:A1991FZ45500061 PM 1905503 ER PT J AU OLIVER, AE DEAMER, DW AKESON, M AF OLIVER, AE DEAMER, DW AKESON, M TI SENSITIVITY TO ANESTHESIA BY PREGNANOLONE APPEARS LATE IN EVOLUTION SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Note ID MECHANISMS C1 NIMH,MOLEC BIOL LAB,BETHESDA,MD 20892. RP OLIVER, AE (reprint author), UNIV CALIF DAVIS,DEPT ZOOL,DAVIS,CA 95616, USA. NR 9 TC 5 Z9 5 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD JUN 28 PY 1991 VL 625 BP 561 EP 565 DI 10.1111/j.1749-6632.1991.tb33891.x PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FZ455 UT WOS:A1991FZ45500067 PM 2058910 ER PT J AU BIRCH, NP LOH, YP AF BIRCH, NP LOH, YP TI HOMOLOGY CLONING OF ASPARTIC PROTEASES FROM AN ENDOCRINE CELL-LINE USING THE POLYMERASE CHAIN-REACTION SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID LOBE SECRETORY VESICLES; GASTRIC CATHEPSIN-E; FULL-LENGTH CDNA; CONVERTING ENZYME; SEQUENCE-ANALYSIS; NUCLEOTIDE-SEQUENCE; MOLECULAR-CLONING; PURIFICATION; LOCALIZATION; PEPSINOGEN RP BIRCH, NP (reprint author), NICHHD,DEV NEUROBIOL LAB,CELLULAR NEUROBIOL SECT,BLDG 36,RM 2A21,BETHESDA,MD 20892, USA. RI Birch, Nigel/H-2498-2011 OI Birch, Nigel/0000-0002-8417-3587 NR 22 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 28 PY 1991 VL 177 IS 3 BP 920 EP 926 DI 10.1016/0006-291X(91)90626-I PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FU526 UT WOS:A1991FU52600005 PM 2059219 ER PT J AU PRASAD, GL MEISSNER, S SHEER, DG COOPER, HL AF PRASAD, GL MEISSNER, S SHEER, DG COOPER, HL TI A CDNA-ENCODING A MUSCLE-TYPE TROPOMYOSIN CLONED FROM A HUMAN EPITHELIAL-CELL LINE - IDENTITY WITH HUMAN FIBROBLAST TROPOMYOSIN TM1 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CARCINOEMBRYONIC ANTIGEN; EXPRESSION; ALPHA; GENE; NONMUSCLE; ISOFORMS; SUPPRESSION; B72.3 C1 NCI,TUMOR IMMUNOL & BIOL LAB,CELL & MOLEC PHYSIOL SECT,BETHESDA,MD 20892. NR 24 TC 25 Z9 26 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 JUN 28 PY 1991 VL 177 IS 3 BP 1068 EP 1075 DI 10.1016/0006-291X(91)90647-P PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FU526 UT WOS:A1991FU52600026 PM 2059197 ER PT J AU COOKE, DW BANKERT, LA ROBERTS, CT LEROITH, D CASELLA, SJ AF COOKE, DW BANKERT, LA ROBERTS, CT LEROITH, D CASELLA, SJ TI ANALYSIS OF THE HUMAN TYPE-I INSULIN-LIKE GROWTH-FACTOR RECEPTOR PROMOTER REGION SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MESSENGER-RNAS; THYROID-HORMONE; GENE; BINDING; TRANSCRIPTION; SEQUENCE; TRANSLATION; EXPRESSION; INDUCTION; CELLS C1 NIH,DIABET BRANCH,BETHESDA,MD 20892. RP COOKE, DW (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,CMSC 3-110,BALTIMORE,MD 21205, USA. OI Roberts, Charles/0000-0003-1756-5772 FU NIDDK NIH HHS [R29DK38542] NR 32 TC 76 Z9 82 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 JUN 28 PY 1991 VL 177 IS 3 BP 1113 EP 1120 DI 10.1016/0006-291X(91)90654-P PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FU526 UT WOS:A1991FU52600033 PM 1711844 ER PT J AU TORTORA, G PEPE, S YOKOZAKI, H MEISSNER, S CHOCHUNG, YS AF TORTORA, G PEPE, S YOKOZAKI, H MEISSNER, S CHOCHUNG, YS TI COOPERATIVE EFFECT OF 8-CL-CAMP AND RHGM-CSF ON THE DIFFERENTIATION OF HL-60 HUMAN LEUKEMIA-CELLS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID DEPENDENT PROTEIN-KINASE; SELECTIVE CAMP ANALOGS; AMINO-ACID SEQUENCE; CYCLIC-AMP; REGULATORY SUBUNIT; ADENOSINE-MONOPHOSPHATE; MOLECULAR-CLONING; GENE-EXPRESSION; BINDING-SITES; MESSENGER-RNA C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. OI Yokozaki, Hiroshi/0000-0001-5276-3331 NR 36 TC 21 Z9 21 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 28 PY 1991 VL 177 IS 3 BP 1133 EP 1140 DI 10.1016/0006-291X(91)90657-S PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FU526 UT WOS:A1991FU52600036 PM 2059204 ER PT J AU HIRAIWA, M UDA, Y TSUJI, S MIYATAKE, T MARTIN, BM TAYAMA, M OBRIEN, JS KISHIMOTO, Y AF HIRAIWA, M UDA, Y TSUJI, S MIYATAKE, T MARTIN, BM TAYAMA, M OBRIEN, JS KISHIMOTO, Y TI HUMAN PLACENTAL SIALIDASE COMPLEX - CHARACTERIZATION OF THE 60 KDA PROTEIN THAT CROSS-REACTS WITH ANTI-SAPOSIN ANTIBODIES SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID BETA-GALACTOSIDASE; LYSOSOMAL NEURAMINIDASE; PROTECTIVE PROTEIN; ACTIVATOR; SEQUENCE; CDNA C1 UNIV CALIF SAN DIEGO,CTR MOLEC GENET,DEPT NEUROSCI,LA JOLLA,CA 92093. NIIGATA COLL PHARM,DEPT HLTH CHEM,NIIGATA 95021,JAPAN. NIIGATA UNIV,INST BRAIN RES,DEPT NEUROL,NIIGATA 951,JAPAN. NIMH,MOLEC NEUROGENET UNIT,BETHESDA,MD 20892. FU NICHD NIH HHS [HD-18983]; NINDS NIH HHS [NS-13559, NS-08682] NR 19 TC 16 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 28 PY 1991 VL 177 IS 3 BP 1211 EP 1216 DI 10.1016/0006-291X(91)90670-3 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FU526 UT WOS:A1991FU52600049 PM 1905536 ER PT J AU SNYDER, CE AF SNYDER, CE TI AMINO-ACID-SEQUENCE OF THE BACTERIOPHAGE-T5 GENE A2 PROTEIN SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID DNA-BINDING PROTEINS; ESCHERICHIA-COLI; RNA-POLYMERASE; OUTER-MEMBRANE; REPRESSOR; OMPF RP SNYDER, CE (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,CLIN IMMUNOL SERV,PEPTIDE SYNTH LAB,FREDERICK,MD 21702, USA. FU PHS HHS [N01-C0-74102] NR 27 TC 1 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 28 PY 1991 VL 177 IS 3 BP 1240 EP 1246 DI 10.1016/0006-291X(91)90674-V PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FU526 UT WOS:A1991FU52600053 PM 2059212 ER PT J AU HERKENHAM, M GROEN, BGS LYNN, AB DECOSTA, BR RICHFIELD, EK AF HERKENHAM, M GROEN, BGS LYNN, AB DECOSTA, BR RICHFIELD, EK TI NEURONAL LOCALIZATION OF CANNABINOID RECEPTORS AND 2ND MESSENGERS IN MUTANT MOUSE CEREBELLUM SO BRAIN RESEARCH LA English DT Article DE TETRAHYDROCANNABINOL; [H-3]CP-55,940; FORSKOLIN; PHORBOL ESTER; ADENYLATE CYCLASE; PHOSPHOINOSITIDE ID PROTEIN KINASE-C; RAT-BRAIN; ADENYLATE-CYCLASE; BINDING; TETRAHYDROCANNABINOLS; MICE AB Four lines of mutant mice were used to investigate (1) the neuronal localization of cannabinoid receptors in the cerebellar molecular layer and (2) the anatomical association of these receptors with elements of the two second messenger systems in the brain. Two of the mutant lines - Purkinje cell degeneration and nervous - are selectively deficient in Purkinje cells; the other two - weaver and reeler - are deficient in granule cells. In the heterozygous mice, [H-3]CP 55,940 binding to cannabinoid receptors was discretely and densely localized to the molecular layer, as was [H-3]forskolin binding to adenylate cyclase and [H-3]phorbol 12,13-dibutyrate binding to protein kinase C, a component of the phosphoinositide cycle. [H-3]CP 55,940 and [H-3]forskolin binding was selectively reduced in weaver and reeler homozygous mice but unchanged in Purkinje cell deficient and nervous homozygotes. No decreases in [H-3]phorpbol 12,13-dibutyrate binding were found in any of the homozygous mutants relative to the heterozygous littermates. The results suggest that cannabinoid receptors and adenylate cyclase are localized to granule cell axons in the molecular layer, whereas protein kinase C is equally distributed in parallel fibers and Purkinje cell dendrites. C1 NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. RP HERKENHAM, M (reprint author), NIMH,FUNCT NEUROANAT SECT,BLDG 36,RM 2D-15,BETHESDA,MD 20892, USA. NR 32 TC 71 Z9 73 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUN 28 PY 1991 VL 552 IS 2 BP 301 EP 310 DI 10.1016/0006-8993(91)90096-E PG 10 WC Neurosciences SC Neurosciences & Neurology GA FV305 UT WOS:A1991FV30500015 PM 1913192 ER PT J AU PONS, TP GARRAGHTY, PE OMMAYA, AK KAAS, JH TAUB, E MISHKIN, M AF PONS, TP GARRAGHTY, PE OMMAYA, AK KAAS, JH TAUB, E MISHKIN, M TI MASSIVE CORTICAL REORGANIZATION AFTER SENSORY DEAFFERENTATION IN ADULT MACAQUES SO SCIENCE LA English DT Article ID SOMATOSENSORY CORTEX; OWL MONKEYS; AREA 3B; ORGANIZATION; REPRESENTATIONS; CONNECTIONS; MAMMALS; LESIONS; HAND; BODY AB After limited sensory deafferentations in adult primates, somatosensory cortical maps reorganize over a distance of 1 to 2 millimeters mediolaterally, that is, in the dimension along which different body parts are represented. This amount of reorganization was considered to be an upper limit imposed by the size of the projection zones of individual thalamocortical axons, which typically also extend a mediolateral distance of 1 to 2 millimeters. However, after extensive long-term deafferentations in adult primates, changes in cortical maps were found to be an order of magnitude greater than those previously described. These results show the need for a reevaluation of both the upper limit of cortical reorganization in adult primates and the mechanisms responsible for it. C1 UNIV ALABAMA,DEPT PSYCHOL,BIRMINGHAM,AL 35294. VANDERBILT UNIV,DEPT PSYCHOL,NASHVILLE,TN 37240. RP PONS, TP (reprint author), NIMH,NEUROPSYCHOL LAB,BLDG 9,ROOM 1N107,BETHESDA,MD 20892, USA. NR 31 TC 713 Z9 729 U1 4 U2 53 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 28 PY 1991 VL 252 IS 5014 BP 1857 EP 1860 DI 10.1126/science.1843843 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FU061 UT WOS:A1991FU06100043 PM 1843843 ER PT J AU FIELD, MJ AF FIELD, MJ TI CONSTRAINED OPTIMIZATION OF ABINITIO AND SEMIEMPIRICAL HARTREE-FOCK WAVE-FUNCTIONS USING DIRECT MINIMIZATION OR SIMULATED ANNEALING SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID MOLECULAR-DYNAMICS; VARIATIONAL CALCULATION; ENERGIES; STRATEGY AB A method recently developed for the simultaneous minimization of the energy of a quantum mechanical system with respect to its nuclear coordinates and the variables that determine its wave function is extended to include ab initio Hartree-Fock wave functions. The orthonormality constraints on the molecular orbitals are enforced by using an iterative technique, SHAKE, and it is shown how extra constraints that permit the calculation of excited-state wave functions can be introduced. The results of a small number of calculations are presented as examples to illustrate the direct minimization and classical molecular dynamics/simulated annealing optimization procedures. RP FIELD, MJ (reprint author), NIH,DIV COMP RES & TECHNOL,BLDG 12A,BETHESDA,MD 20892, USA. NR 27 TC 33 Z9 33 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3654 J9 J PHYS CHEM-US JI J. Phys. Chem. PD JUN 27 PY 1991 VL 95 IS 13 BP 5104 EP 5108 DI 10.1021/j100166a037 PG 5 WC Chemistry, Physical SC Chemistry GA FU291 UT WOS:A1991FU29100037 ER PT J AU STEWART, WW FEDER, N AF STEWART, WW FEDER, N TI ANALYSIS OF A WHISTLE-BLOWING SO NATURE LA English DT Editorial Material ID IMMUNOGLOBULIN GENE; EXPRESSION; ANTIBODY RP STEWART, WW (reprint author), NIH,BETHESDA,MD 20892, USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD JUN 27 PY 1991 VL 351 IS 6329 BP 687 EP 691 DI 10.1038/351687a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FU201 UT WOS:A1991FU20100029 PM 1905785 ER PT J AU PROBSTFIELD, JL AF PROBSTFIELD, JL TI PREVENTION OF STROKE BY ANTIHYPERTENSIVE DRUG-TREATMENT IN OLDER PERSONS WITH ISOLATED SYSTOLIC HYPERTENSION - FINAL RESULTS OF THE SYSTOLIC HYPERTENSION IN THE ELDERLY PROGRAM (SHEP) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MORTALITY; TRIAL; POPULATION; OSLO; CARE; RISK AB Objective. - To assess the ability of antihypertensive drug treatment to reduce the risk of nonfatal and fatal (total) stroke in isolated systolic hypertension. Design. - Multicenter, randomized, double-blind, placebo-controlled. . Setting. - Community-based ambulatory population in tertiary care centers. Participants. - 4736 persons (1.06%) from 447 921 screenees aged 60 years and above were randomized (2365 to active treatment, 2371 to placebo). Systolic blood pressure ranged from 160 to 219 mm Hg and diastolic blood pressure was less than 90 mm Hg. Of the participants, 3161 were not receiving antihypertensive medication at initial contact, and 1575 were. The average systolic blood pressure was 170 mm Hg; average diastolic blood pressure, 77 mm Hg. The mean age was 72 years, 57% were women, and 14% were black. Interventions. - Participants were stratified by clinical center and by antihypertensive medication status at initial contact. For step 1 of the trial, dose 1 was chlorthalidone, 12.5 mg/d, or matching placebo; dose 2 was 25 mg/d. For step 2, dose 1 was atenolol, 25 mg/d, or matching placebo; dose 2 was 50 mg/d. Main Outcome Measures. - Primary. - Nonfatal and fatal (total) stroke. Secondary. - Cardiovascular and coronary morbidity and mortality, all-cause mortality, and quality of life measures. Results. - Average follow-up was 4.5 years. The 5-year average systolic blood pressure was 155 mm Hg for the placebo group and 143 mm Hg for the active treatment group, and the 5-year average diastolic blood pressure was 72 and 68 mm Hg, respectively. The 5-year incidence of total stroke was 5.2 per 100 participants for active treatment and 8.2 per 100 for placebo. The relative risk by proportional hazards regression analysis was 0.64 (P = .0003). For the secondary end point of clinical nonfatal myocardial infarction plus coronary death, the relative risk was 0.73. Major cardiovascular events were reduced (relative risk, 0.68). For deaths from all causes, the relative risk was 0.87. Conclusion. - In persons aged 60 years and over with isolated systolic hypertension, antihypertensive stepped-care drug treatment with low-dose chlorthalidone as step 1 medication reduced the incidence of total stroke by 36%, with 5-year absolute benefit of 30 events per 1 000 participants. Major cardiovascular events were reduced, with 5-year absolute benefit of 55 events per 1000. RP PROBSTFIELD, JL (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,CLIN TRIALS BRANCH,FED BLDG,BETHESDA,MD 20892, USA. NR 51 TC 2448 Z9 2496 U1 3 U2 40 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 JUN 26 PY 1991 VL 265 IS 24 BP 3255 EP 3264 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA FR835 UT WOS:A1991FR83500031 ER PT J AU KORZEKWA, KR TRAGER, WF SMITH, SJ OSAWA, Y GILLETTE, JR AF KORZEKWA, KR TRAGER, WF SMITH, SJ OSAWA, Y GILLETTE, JR TI THEORETICAL-STUDIES ON THE MECHANISM OF CONVERSION OF ANDROGENS TO ESTROGENS BY AROMATASE SO BIOCHEMISTRY LA English DT Article ID HUMAN PLACENTAL MICROSOMES; CYTOCHROME-P-450 REACTION; VALPROIC ACID; MODEL; BIOSYNTHESIS; AROMATIZATION; INHIBITION; INACTIVATION; TESTOSTERONE; DERIVATIVES AB Semiempirical molecular orbital calculations (AM1) were used to model several possible reaction mechanisms for the third oxidation of the aromatase-catalyzed conversion of androgens to estrogens. The reaction mechanisms considered are based on the assumption that the third oxidation is initiated by 1-beta-hydrogen atom abstraction. Homolytic cleavage of the C-10-C19 bond was modeled for both the 3-keto and 2-en-3-ol forms of the androgen 1-radicals. The addition of a protein nucleophile to the 19-oxo intermediate was also considered, and -OCH3, -SCH3, and -NHCH3 were used to represent the Ser, Cys, and Lys adducts. The transition states were estimated and optimized from the reaction coordinates obtained by constraining and increasing the C-10-C19 bond lengths. The enthalpies of activation range from 14 to 21 kcal and are approximately 2 kcal lower for cleavage of the enol form. Given the tendency for AM1 to overestimate activation energies, all reactions may be energetically accessible. Other reactions modeled include a homolytic cleavage reaction from a thioether radical cation and the direct additions of oxygen radical compounds to the carbonyl of the 1-radical-2-en-3-ol-19-oxo androgen. A mechanism is proposed in which the 19-oxo intermediate is subject to initial nucleophilic attack by the protein. Since rotation of the 19-carbonyl can bring the oxygen within 2.1 angstrom of the 2-beta-hydrogen, the formation of a tetrahedral intermediate can occur with concomitant removal of the 2-beta-proton. Enolization activates the C1-position for hydrogen atom abstraction, since the resulting radical is resonance stabilized. Homolytic cleavage of this radical is followed by recombination of the C19-radical with the hydroxy radical equivalent. The geometry of the carbonyl oxygen in the androgens is between that for the 1-radicals and estrogen, suggesting that some transition-state stabilization for the homolytic cleavage reaction may occur. C1 NHLBI,CHEM PHARMACOL LAB,BETHESDA,MD 20892. UNIV WASHINGTON,DEPT MED CHEM,SEATTLE,WA 98195. FU NIGMS NIH HHS [GM36922] NR 38 TC 28 Z9 30 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 JUN 25 PY 1991 VL 30 IS 25 BP 6155 EP 6162 DI 10.1021/bi00239a011 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FT936 UT WOS:A1991FT93600011 PM 1647815 ER PT J AU ROSS, PD HOWARD, FB LEWIS, MS AF ROSS, PD HOWARD, FB LEWIS, MS TI THERMODYNAMICS OF ANTIPARALLEL HAIRPIN DOUBLE HELIX EQUILIBRIA IN DNA OLIGONUCLEOTIDES FROM EQUILIBRIUM ULTRACENTRIFUGATION SO BIOCHEMISTRY LA English DT Article AB Five highly palindromic DNA dodecamers, four of which may form G-A or I-A purine - purine mispairs at either the 5,8 or 6,7 positions, have been studied at sedimentation equilibrium in the analytical ultracentrifuge. Each DNA oligonucleotide forms an equilibrium mixture of ordered antiparallel hairpin and double-stranded helical structures in solutions of 0.1 or 0.5 M NaCl between 5 and 40-degrees-C. The dimeric duplex is favored by conditions of high salt and low temperature. The monomer - dimer equilibrium constants vary from 5 x 10(6) to 5 X 10(3) and are unique for each DNA dodecamer. Analysis of the temperature dependence of the equilibrium constants shows that the double helix to hairpin conversion is driven by a positive entropy change and is associated with an endothermic enthalpy change. The mispair substitutions at the 5,8 positions and the IA(6,7) mispair have the greatest tendency toward hairpin formation and exhibit significantly larger entropy changes than the nonmispaired dGGTACGCGTACC parent sequence and the thermodynamically similar GA(6,7) DNA. The consequences of such hairpin - double helix equilibria must be considered in the interpretation of other kinds of experiments carried out on oligonucleotides at different concentrations. C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RP ROSS, PD (reprint author), NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 11 TC 13 Z9 13 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 JUN 25 PY 1991 VL 30 IS 25 BP 6269 EP 6275 DI 10.1021/bi00239a027 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FT936 UT WOS:A1991FT93600027 PM 2059633 ER PT J AU WIDEN, SG WILSON, SH AF WIDEN, SG WILSON, SH TI MAMMALIAN BETA-POLYMERASE PROMOTER - LARGE-SCALE PURIFICATION AND PROPERTIES OF ATF/CREB PALINDROME BINDING-PROTEIN FROM BOVINE TESTES SO BIOCHEMISTRY LA English DT Article ID REPRESSOR-OPERATOR INTERACTION; AMP RESPONSE ELEMENT; NUCLEAR FACTOR CREB; ATF CDNA CLONES; CYCLIC-AMP; MESSENGER-RNA; DNA; TRANSCRIPTION; FAMILY; GENE AB The mammalian DNA repair enzyme beta-polymerase is encoded by a single-copy gene that is expressed in all tissues and cell lines studied to date. A protein fraction with high binding affinity for an ATF/CREB-like binding element, GTGACGTCAC, at -49 to -40 in the core beta-polymerase promoter has been purified to near-homogeneity from a nuclear extract of bovine testes. The major binding activity, as monitored by gel mobility shift assay, is recovered in 20% yield by a procedure involving oligonucleotide affinity chromatography. The purified protein yields DNase I footprinting and gel shift binding patterns indistinguishable from the activity in crude extracts. The final fraction activates transcription in an in vitro transcription reaction. The native molecular weight of the purified binding activity is about 100-120K as measured by gel filtration. SDS-PAGE of the purified fraction revealed that it contains several polypeptides in the molecular weight range of 30-52K, yet two of these peptides (M(r) 49K and 52K) are predominant. Specific binding to the palindrome is salt-sensitive and is consistent with the formation of nine ion pairs (from log K(A) vs log KCl plots) and has a KA at 200 mM KCl of 5.8 X 10(11) M-1. Kinetic studies with synthetic oligonucleotides as binding ligands indicate that the purified protein can bind tighter to or discriminate between the beta-polymerase ATF/CREB element and similar elements derived from somatostatin and chorionic gonadotropin genes. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 30 TC 38 Z9 40 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 JUN 25 PY 1991 VL 30 IS 25 BP 6296 EP 6305 DI 10.1021/bi00239a031 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FT936 UT WOS:A1991FT93600031 PM 1829381 ER PT J AU EGAN, MF KAROUM, F WYATT, RJ AF EGAN, MF KAROUM, F WYATT, RJ TI EFFECTS OF ACUTE AND CHRONIC CLOZAPINE AND HALOPERIDOL ADMINISTRATION ON 3-METHOXYTYRAMINE ACCUMULATION IN RAT PREFRONTAL CORTEX, NUCLEUS-ACCUMBENS AND STRIATUM SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE NEUROLEPTICS (CHRONIC); HALOPERIDOL; CLOZAPINE; 3-METHOXYTYRAMINE ID DECREASES DOPAMINE RELEASE; SCHIZOPHRENIC-PATIENTS; FRONTAL-CORTEX; ANTIPSYCHOTIC-DRUGS; HOMOVANILLIC-ACID; NEUROLEPTICS; NEURONS; CHLORPROMAZINE; METABOLISM; INVIVO AB The accumulation of 3-methoxytyramine (3-MT), a reflection of dopamine release, was measured in the prefrontal cortex, nucleus accumbens, and striatum following administration of acute and chronic clozapine and haloperidol. Several doses of each drug were used. The effects of chronic drug treatment were measured 1 h (chronic 1 h groups), 24 h (chronic 24 h groups) and 48 h (chronic 48 h groups) after the final dose of each drug. In the prefrontal cortex, clozapine and haloperidol elevated 3-MT more in the acute groups than in the chronic 1 h groups, suggesting that partial tolerance developed. In the striatum and nucleus accumbens, acute and chronic (chronic 1 h) haloperidol produced equal increases in 3-MT above the appropriate baselines, suggesting that no tolerance developed. In the striatum, clozapine reduced 3-MT in the chronic 1 h group after high doses (25 mg/kg), and in the chronic 24 h group. These results suggest that neuroleptics may not produce the reduction in dopamine release that has been predicted with the development of depolarization inactivation. The reduction of striatal dopamine release during chronic clozapine treatment may be related to clozapine not being associated with the development of tardive dyskinesia. RP EGAN, MF (reprint author), ST ELIZABETH HOSP,NEUROSCI RES CTR,NIMH,NEUROPSYCHIAT BRANCH,WAW BLDG,ROOM 502,WASHINGTON,DC 20032, USA. NR 56 TC 30 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JUN 25 PY 1991 VL 199 IS 2 BP 191 EP 199 DI 10.1016/0014-2999(91)90457-2 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FV895 UT WOS:A1991FV89500007 PM 1954977 ER PT J AU HETTASCH, JM SELLERS, JR AF HETTASCH, JM SELLERS, JR TI CALDESMON PHOSPHORYLATION IN INTACT HUMAN PLATELETS BY CAMP-DEPENDENT PROTEIN-KINASE AND PROTEIN-KINASE-C SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SMOOTH-MUSCLE CALDESMON; CALMODULIN-BINDING PROTEIN; NONMUSCLE CALDESMON; ADENYLATE-CYCLASE; MOLECULAR-WEIGHT; BLOOD-PLATELETS; ATPASE ACTIVITY; THIN-FILAMENTS; F-ACTIN; MYOSIN AB Caldesmon is a calmodulin- and actin-binding protein present in both smooth and non-muscle tissue. The present study demonstrates that platelet caldesmon is a substrate for cAMP-dependent protein kinase (protein kinase A). Purified platelet caldesmon has an apparent molecular mass of 82 kDa on sodium dodecyl sulfate-polyacrylamide gels and can be phosphorylated in vitro by the catalytic subunit of protein kinase A to a level of 2 mol of phosphate/mol of caldesmon. Phosphorylation of caldesmon by protein kinase A results in a shift in the apparent molecular mass of the protein to 86 kDa. When caldesmon was immunoprecipitated from intact platelets treated with prostacyclin (PGI2) the same shift in apparent molecular mass of caldesmon was observed. Comparison of two-dimensional tryptic phosphopeptide maps of caldesmon phosphorylated in vitro by protein kinase A with caldesmon immunoprecipitated from intact platelets verified that protein kinase A was responsible for the observed increase in caldesmon phosphorylation in PGI2-treated platelets. The present study demonstrates that although caldesmon is basally phosphorylated in the intact platelet, activation of protein kinase A by PGI2 results in the significant incorporation of phosphate into two new sites. In addition, the effects of phorbol ester, collagen, and thrombin on caldesmon phosphorylation were also examined. Although phorbol ester treatment results in a significant increase in caldesmon phosphorylation apparently by protein kinase C, treatment of intact platelets with thrombin or collagen does not result in an increase in caldesmon phosphorylation. C1 NHLBI,MOLEC CARDIOL LAB,BETHESDA,MD 20892. NR 52 TC 33 Z9 34 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 JUN 25 PY 1991 VL 266 IS 18 BP 11876 EP 11881 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FT762 UT WOS:A1991FT76200071 PM 2050683 ER PT J AU BUSHKIN, I ROTH, J HEFFETZ, D ZICK, Y AF BUSHKIN, I ROTH, J HEFFETZ, D ZICK, Y TI PP75 - A NOVEL TYROSINE-PHOSPHORYLATED PROTEIN THAT HERALDS DIFFERENTIATION OF HL-60 CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROMYELOCYTIC LEUKEMIA-CELLS; INSULIN-RECEPTOR KINASE; MONOCYTIC DIFFERENTIATION; GM-CSF; LINE; EXPRESSION; MATURATION; H2O2; INTERLEUKIN-3; PURIFICATION AB The human promyeloid cell line HL-60 differentiates toward monocytes or granulocytes when treated with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) or dibutyryl cAMP, respectively. When nondifferentiated cells were incubated for 20 min with 2 mm H2O2 and 0.1 mm sodium orthovanadate to inhibit their protein-tyrosine-phosphatase activity (Heffetz, D., Bushkin, I., Dror, R., and Zick, Y. (1990) J. Biol. Chem. 265, 2896-2902), we found marked tyrosine phosphorylation of a single major protein of 53 kDa. Induction of differentiation of HL-60 cells was accompanied by the appearance of an additional major cytosolic tyrosine-phosphorylated protein of 75 kDa (pp75). In dibutyryl cAMP-treated cells, tyrosine phosphorylation of pp75 peaked after 24 h and then declined rapidly. In 1,25(OH)2D3-treated cells, increased tyrosine phosphorylation was detected as early as 2 h and peaked after 3 days, whereas the presence of differentiated phenotypes, assessed by the capacity of the cells to reduce nitro blue tetrazolium, was detected no earlier than 24 h. Doses of 1,25(OH)2D3 as low as 1 nM induced the appearance of pp75 at a stage where almost no differentiation measured by nitro blue tetrazolium reduction was detected. Phosphorylation of pp75 was not stimulated by adriamycin, which induced growth arrest without initiation of differentiation. pp75 could also be detected in U-937, a monocytic cell line that is more advanced in its differentiation state, and also in terminally differentiated circulating human monocytes treated with H2O2/Vanadate. pp75 underwent in vitro tyrosine phosphorylation in cytosolic extracts derived from 1,25(OH)2D3-induced HL-60 cells, but not in extracts derived from uninduced cells. Our results raise the possibility that tyrosine phosphorylation of pp75 may be a common early event that heralds the differentiation of HL-60 cells into both the monocytic and granulocytic pathways. C1 WEIZMANN INST SCI,DEPT CHEM IMMUNOL,IL-76100 REHOVOT,ISRAEL. NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. NR 31 TC 19 Z9 19 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 JUN 25 PY 1991 VL 266 IS 18 BP 11890 EP 11895 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FT762 UT WOS:A1991FT76200073 PM 2050685 ER PT J AU MCDONAGH, KT LIN, HJ LOWREY, CH BODINE, DM NIENHUIS, AW AF MCDONAGH, KT LIN, HJ LOWREY, CH BODINE, DM NIENHUIS, AW TI THE UPSTREAM REGION OF THE HUMAN GAMMA-GLOBIN GENE PROMOTER - IDENTIFICATION AND FUNCTIONAL-ANALYSIS OF NUCLEAR-PROTEIN BINDING-SITES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STAGE-SPECIFIC EXPRESSION; GREEK HEREDITARY PERSISTENCE; RNA POLYMERASE-II; BETA-GLOBIN; TRANSGENIC MICE; TRANSCRIPTION FACTOR; FETAL HEMOGLOBIN; DEVELOPMENTAL REGULATION; ERYTHROID-CELLS; 3' ENHANCER AB The promoter of the human gamma-globin gene confers tissue specificity as well as developmental stage specificity to gamma-gene expression. Earlier work in our laboratory suggested that a fragment of the gamma-globin promoter between -300 and -137 base pairs upstream of the transcription start site contributed to the developmental specificity of the promoter. In this paper, we have mapped potential regulatory elements within this upstream region of the gamma-promoter by a combination of in vitro DNA-protein binding assays and functional determinations of promoter strength in transient expression studies. Four sites between -300 and - 130 bind proteins present in nuclear extracts of erythroid and non-erythroid cell lines. Mutation of these binding sites by internal base substitution determined that three of the four influence overall promoter strength in transient assays. We have focused on two protein binding sites, -246 to -212 and -195 to -170, that have been reported to bind erythroid-specific factors. The erythroid binding protein NF-E1 and a ubiquitous octamer protein footprint the -195 to -170 site. While internal mutation of this site did not significantly alter promoter strength, a point mutation at position -175 that is associated with hereditary persistence of fetal hemoglobin increased the activity of a promoter construct 20-fold in erythroid cells. A detailed mutational analysis of this site suggests that NF-E1 binding is necessary but not sufficient for activation of the promoter by the -175 mutation, and we propose that a second protein or co-activator is required. The nucleotides between -246 and -212 appear to bind a complex of at least three proteins, at the core of which is a protein binding to a string of dA:dT residues. This complex also appears to form on the 3' A-gamma-globin enhancer, and homologous sites have been identified within the locus activating region of the beta-globin cluster, suggesting that this element may mediate long range interactions with distant regulatory elements. C1 UNIV CALIF LOS ANGELES,HARBOR MED CTR,DIV MED GENET,TORRANCE,CA 90502. RP MCDONAGH, KT (reprint author), NHLBI,CLIN HEMATOL BRANCH,BLDG 10,RM 7C103,BETHESDA,MD 20892, USA. NR 61 TC 40 Z9 41 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 25 PY 1991 VL 266 IS 18 BP 11965 EP 11974 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FT762 UT WOS:A1991FT76200083 PM 2050690 ER PT J AU DONOFRIO, M LEE, MD STARR, CM MILLER, M HANOVER, JA AF DONOFRIO, M LEE, MD STARR, CM MILLER, M HANOVER, JA TI THE GENE ENCODING RAT NUCLEAR-PORE GLYCOPROTEIN P62 IS INTRONLESS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LINKED N-ACETYLGLUCOSAMINE; MONOCLONAL-ANTIBODIES; COMPLEX GLYCOPROTEINS; PROTEIN; SEQUENCE; CDNA; TRANSPORT; FAMILY; RECEPTOR; REGIONS AB Glycoproteins of the nuclear pore complex are thought to play an important role in the transport of regulatory proteins and ribonucleoproteins across the nuclear envelope. However, the genetic elements and signals that control the expression of nuclear pore glycoproteins are poorly understood. To study the transcriptional regulation of mammalian nuclear pore glycoprotein biosynthesis, we have isolated the gene coding for the major rat nuclear pore glycoprotein p62. The p62 gene consists of a 2941-base pair region that is linear with the full length p62 cDNA with no intervening sequences. Quantitative Southern analysis revealed that the gene is present in single copy. The p62 gene encodes a 525-amino acid open reading frame that directs the synthesis of the 62-kDa pore glycoprotein in vitro and in transfected cultured cells. The 5'-flanking region contains two potential transcription start sites; primer extension analysis revealed that the furthest upstream site is preferentially used in vivo. When linked to a reporter gene, the 5'-flanking region of the p62 gene serves as an active promoter. C1 NIDDKD,BIOCHEM & METAB LAB,BLDG 10,RM 9B15,BETHESDA,MD 20892. NR 43 TC 9 Z9 10 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 JUN 25 PY 1991 VL 266 IS 18 BP 11980 EP 11985 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FT762 UT WOS:A1991FT76200085 PM 2050692 ER PT J AU WINSLOW, SG HENKART, PA AF WINSLOW, SG HENKART, PA TI POLYINOSINIC ACID AS A CARRIER IN THE MICROSCALE PURIFICATION OF TOTAL RNA SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SMALL NUMBERS; SINGLE; CELLS AB Three different RNA carriers were compared for use in microscale RNA isolation and subsequent cDNA synthesis and amplification via the polymerase chain reaction. E. coli rRNA along gave considerable cDNA synthesis which under standard carrier conditions overwhelmed cDNA synthesis from lymphocyte mRNA. Yeast tRNA caused inhibition of mRNA primed cDNA synthesis, giving low levels of cDNA synthesis when used without cellular RNA. In contrast, commercially available poly I alone did not prime detectable cDNA synthesis nor did it inhibit such synthesis primed by cellular mRNA. When RNA preparations were made using these three carriers and decreasing numbers of starting lymphocytes, poly I allowed the detection of cDNA from two orders of magnitude fewer lymphocytes than the other carriers. Thus poly I was found to be a superior carrier molecule for microscale RNA preparations suitable for reverse transcription and subsequent amplification using the polymerase chain reaction. RP WINSLOW, SG (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B17,BETHESDA,MD 20892, USA. NR 6 TC 22 Z9 23 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN 25 PY 1991 VL 19 IS 12 BP 3251 EP 3253 DI 10.1093/nar/19.12.3251 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FU512 UT WOS:A1991FU51200011 PM 1712097 ER PT J AU ENGLANDER, EW WIDEN, SG WILSON, SH AF ENGLANDER, EW WIDEN, SG WILSON, SH TI MAMMALIAN BETA-POLYMERASE PROMOTER - PHOSPHORYLATION OF ATF/CRE-BINDING PROTEIN AND REGULATION OF DNA-BINDING SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TRANSCRIPTION FACTOR CREB; AMP RESPONSE ELEMENT; NUCLEAR FACTOR CREB; ATF CDNA CLONES; CYCLIC-AMP; GENE-EXPRESSION; CELLS; KINASE; RECOGNITION; ACTIVATION AB The gene for the mammalian DNA repair enzyme DNA polymerase beta (beta-pol) is constitutively expressed in most cells, but is regulated in a tissue-specific fashion and can be induced in response to some types of DNA damaging agents. The promoter for the human beta-pol gene has been characterized and found to be TATA-less, but it does have multiple GC boxes and one ATF/CRE-binding site located within 50 residues 5' of the major mRNA start site. The ATF/CRE-binding site has been found to be essential for activity of the cloned promoter. We report that a bovine testes DNA-binding protein with specificity for the beta-pol promoter AFT/CRE-binding site is phosphorylated in vivo and contains several phosphorylation sites. Sequence specific DNA-binding by the purified protein is reduced when the natural protein is dephosphorylated or when it is hyperphosphorylated by protein kinase A (cKA) in vitro. These results suggest the possibility that phosphorylation systems may change binding of this ATF/CRE-binding protein to the beta-pol promoter and in turn modulate the promoter. Possible correlation of the results with transient expression activity of the cloned beta-pol promoter fusion gene was obtained in 293 cells. Cotransfection with a cKA expression plasmid to elevate phosphorylation was found to strongly reduce promoter activity. RP ENGLANDER, EW (reprint author), NCI,BIOCHEM LAB,BETHESDA,MD 20892, USA. NR 40 TC 19 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN 25 PY 1991 VL 19 IS 12 BP 3369 EP 3375 DI 10.1093/nar/19.12.3369 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FU512 UT WOS:A1991FU51200029 PM 1829517 ER PT J AU SANDBERG, K JI, H MILLAN, MA CATT, KJ AF SANDBERG, K JI, H MILLAN, MA CATT, KJ TI AMPHIBIAN MYOCARDIAL ANGIOTENSIN-II RECEPTORS ARE DISTINCT FROM MAMMALIAN AT1 AND AT2 RECEPTOR SUBTYPES SO FEBS LETTERS LA English DT Article DE ANGIOTENSIN RECEPTOR; ANGIOTENSIN; ANGIOTENSIN RECEPTOR ANTAGONIST; XENOPUS-LAEVIS; MYOCARDIUM; HEART ID ADRENAL-CORTEX; IDENTIFICATION; NUCLEOTIDES; BOVINE AB High-affinity receptors for angiotensin 11 were identified on Xenopus laevis cardiac membranes and characterized by binding-inhibition studies with peptide and non-peptide All antagonists. Scatchard analysis of the binding data identified a high-affinity site with K(d1) = 1.6 nM and B(max1) = 3.7 pmol/mg protein and a low-affinity site with K(d2) = 22 nM and B(max2) = 9.5 pmol/mg protein. Treatment with dithiothreitol reduced the number of binding sites by > 70%. The rank order of potency for All analogs was (agent, IC50) [Sar1,Ile8]AII, 0.91 nM > AII, 2.0 nM > AI, 5.3 nM > [Sar1,Ala8]AII, 19 nM >> CGP42112A, 1.2-mu-M >>> DuP 753 almost-equal-to PD-123177, > 100-mu-M. The relative potencies of these compounds differ markedly from their activities on the two known mammalian AII receptor subtypes, AT1, and AT2. These results indicate that amphibian AII receptors are pharmacologically distinct from both the AT1, and AT2, receptors characterized in mammalian tissues. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,BLDG 10,RM B1-L400,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 15 TC 51 Z9 51 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 JUN 24 PY 1991 VL 284 IS 2 BP 281 EP 284 DI 10.1016/0014-5793(91)80704-7 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA FW376 UT WOS:A1991FW37600033 PM 2060651 ER PT J AU PORRINO, LJ VIOLA, JJ CRANE, AM PONTIERI, FE AF PORRINO, LJ VIOLA, JJ CRANE, AM PONTIERI, FE TI ALTERATIONS IN OPIATE RECEPTOR-BINDING IN MPTP-INDUCED HEMIPARKINSONIAN MONKEYS SO NEUROSCIENCE LETTERS LA English DT Article DE OPIATE; RECEPTOR; DOPAMINE; MPTP; [H-3]NALOXONE; STRIATUM; PARKINSONISM; PRIMATE ID PARKINSONS-DISEASE; SUBSTANTIA NIGRA; RAT STRIATUM; BRAIN; LOCALIZATION; LESIONS; ENKEPHALINS; SITES AB Quantitative autoradiography was used to study [H-3]naloxone binding in the striatum of normal monkeys and monkeys made hemiparkinsonian by the unilateral infusion of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The density of [H-3]naloxone binding sites was significantly higher in the caudate and putamen on the MPTP-treated side of hemiparkinsonian monkeys, as compared with binding on the untreated side and in the striatum of normal monkeys. A more extensive patchy distribution of binding sites was evident throughout the striatum on the MPTP-treated side than seen in the striatum of the untreated side or in normal striatum. C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. NIH,HOWARD HUGHES RES INST,BETHESDA,MD 20892. NR 28 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUN 24 PY 1991 VL 127 IS 2 BP 155 EP 159 DI 10.1016/0304-3940(91)90783-P PG 5 WC Neurosciences SC Neurosciences & Neurology GA FV370 UT WOS:A1991FV37000003 PM 1652716 ER PT J AU GUSTAFSON, KR MUNRO, MHG BLUNT, JW CARDELLINA, JH MCMAHON, JB GULAKOWSKI, RJ CRAGG, GM COX, PA BRINEN, LS CLARDY, J BOYD, MR AF GUSTAFSON, KR MUNRO, MHG BLUNT, JW CARDELLINA, JH MCMAHON, JB GULAKOWSKI, RJ CRAGG, GM COX, PA BRINEN, LS CLARDY, J BOYD, MR TI HIV INHIBITORY NATURAL-PRODUCTS .3. DITERPENES FROM HOMALANTHUS-ACUMINATUS AND CHRYSOBALANUS-ICACO SO TETRAHEDRON LA English DT Article ID EUPHORBIA-FIDJIANA; ACAULIS; KAURANE AB Extracts of the tropical rainforest trees Homalanthus acuminatus and Chrysobalanus icaco were active in the NCI AIDS-antiviral screen. Diterpenes 1-4 were found in H. acuminatus, while two (6, 7) were found in C. icaco. Compounds 1 and 6 were active in the anti-HIV screen; 1, 3 and 4 were previously unknown. C1 NCI,FCRDC,DEV THERAPEUT PROGRAM,DRUG DISCOVERY RES & DEV LAB,BLDG 1052,ROOM 121,FREDERICK,MD 21702. NCI,FCRDC,DEV THERAPEUT PROGRAM,NAT PROD BRANCH,FREDERICK,MD 21702. CORNELL UNIV,BAKER LAB,DEPT CHEM,ITHACA,NY 14853. BRIGHAM YOUNG UNIV,DEPT BOT,PROVO,UT 84601. OI Blunt, John/0000-0003-4053-4376 NR 15 TC 49 Z9 54 U1 1 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD JUN 24 PY 1991 VL 47 IS 26 BP 4547 EP 4554 DI 10.1016/S0040-4020(01)86461-9 PG 8 WC Chemistry, Organic SC Chemistry GA FQ470 UT WOS:A1991FQ47000003 ER PT J AU MUFSON, EJ HIGGINS, GA KORDOWER, JH AF MUFSON, EJ HIGGINS, GA KORDOWER, JH TI NERVE GROWTH-FACTOR RECEPTOR IMMUNOREACTIVITY IN THE NEW-WORLD MONKEY (CEBUS-APELLA) AND HUMAN CEREBELLUM SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE PRIMATE; FETAL; AGED; IMMUNOHISTOCHEMISTRY; INSITU HYBRIDIZATION; NEUROTROPHIC ID ADULT-RAT BRAIN; HUMAN BASAL FOREBRAIN; NEUROTROPHIC FACTOR; CHOLINERGIC NEURONS; ALZHEIMERS-DISEASE; NGF RECEPTOR; IMMUNOHISTOCHEMICAL LOCALIZATION; BIOCHEMICAL-CHARACTERIZATION; REGIONAL DISTRIBUTION; FORNIX TRANSECTION AB The present study used the NGFR-5 monoclonal antibody raised against human nerve growth factor receptor (NGFR) to determine the extent of NGFR immunoreactivity within the embryonic and young adult Cebus apella cerebellum as well as the human cerebellum. Immunohistochemically processed tissue revealed NGFR expressing Purkinje cell somata, axons, and dendrites, the latter being observed within the molecular layer of both adult species. Within all regions of the cerebellum we observed both darkly and lightly immunostained Purkinje cells. The proximal axons of these cells, which were visualized for short distances within the granular cell layer, appeared to contain bulbous aggregates of reaction product. In sagittal sections, the full extent of the Purkinje cell dendritic tree was observed in the more lightly stained portions of the cerebellum. In situ hybridization experiments revealed NGFR mRNA within Purkinje cells in a pattern similar to that seen with immunohistochemistry. The distribution of NGFR immunoreactivity within the cerebellum exhibits a general topographic organization with the heaviest and most consistent staining occurring within the archi- and neocerebellum and weaker staining within the paleocerebellum. In fetal Cebus monkey cerebellum obtained at gestational day 50 and 70, NGFR immunoreactivity was observed as a band composed of developing Purkinje cell neurites. These profiles were seen in the paleo- and neocerebellum, but not the archicerebellum. The present investigation is the first demonstration of NGFR immunoreactive profiles in the adult monkey and human cerebellum. These findings suggest that nerve growth factor may influence locomotor and vestibular behaviors that are mediated by cerebellar circuitry. The precise mode of action for the NGF/NGFR system within the cerebellum remains to be determined. C1 CHRISTOPHER CTR PARKINSONS RES,INST BIOGERONTOL RES,SUN CITY,AZ 85372. NIA,BALTIMORE,MD 21224. RP MUFSON, EJ (reprint author), RUSH PRESBYTERIAN ST LUKES MED CTR,DEPT NEUROL SCI,1725 W HARRISON ST,SUITE 1140,CHICAGO,IL 60612, USA. FU NINDS NIH HHS [NS 25655, NS 26146] NR 65 TC 43 Z9 45 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUN 22 PY 1991 VL 308 IS 4 BP 555 EP 575 DI 10.1002/cne.903080405 PG 21 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA FR080 UT WOS:A1991FR08000004 PM 1650799 ER PT J AU LATKER, CH WADHWANI, KC BALBO, A RAPOPORT, SI AF LATKER, CH WADHWANI, KC BALBO, A RAPOPORT, SI TI BLOOD-NERVE BARRIER IN THE FROG DURING WALLERIAN DEGENERATION - ARE AXONS NECESSARY FOR MAINTENANCE OF BARRIER FUNCTION SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE ENDOTHELIAL CELLS; PERINEURIUM; PERMEABILITY; ENDONEURIUM; PERIPHERAL NERVE ID ENDONEURIAL CAPILLARY-PERMEABILITY; SCIATIC-NERVE; PERIPHERAL-NERVE; ENDOTHELIAL-CELLS; MAST-CELLS; FREEZE-SUBSTITUTION; PERINEURIAL CELLS; APOLIPOPROTEIN-E; COMPOUND 48-80; BRAIN-BARRIER AB Blood-nerve barrier tissues (endoneurial blood vessels and perineurium) of the frog's sciatic nerve were studied during chronic Wallerian degeneration to determine whether barrier function depends on the presence of intact axons. Sciatic nerves of adult frogs were transected in the abdominal cavity; the ends were tied to prevent regeneration and the distal nerve stumps were examined. Vascular permeabilities to horseradish peroxidase and to [C-14]sucrose increased to day 14, returned toward normal levels by 6 weeks, and continued at near normal levels to 9 months. Perineurial permeabilities to the tracers increased by day 10 and remained elevated at 9 months. Proliferation of perineurial, endothelial, and mast cells occurred between 3 days and 6 weeks, resulting in an increased vascular space (measured with [H-3]dextran) and number of vascular profiles. The perineurium increased in thickness and the mast cells increased in number. This study indicates that during Wallerian degeneration of the frog's sciatic nerve there is 1) a transitory increase in vascular permeability distal to the lesion, that is related to changes within the endoneurium; 2) an irreversible increase in permeability of the perineurium, which begins later than that seen in the endoneurial blood vessels; and 3) proliferation of non-neuronal components in the absence of regenerating neuronal elements. The results indicate that maintenance of vascular integrity does not require the presence of axons in the frog's peripheral nerve, whereas perineurial integrity and barrier function are affected irreversibly by Wallerian degeneration. C1 NIA,NEUROSCI LAB,BLDG 10,RM 6C103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 80 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUN 22 PY 1991 VL 308 IS 4 BP 650 EP 664 DI 10.1002/cne.903080410 PG 15 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA FR080 UT WOS:A1991FR08000009 PM 1865020 ER PT J AU BERTRAND, R KERRIGAN, D SARANG, M POMMIER, Y AF BERTRAND, R KERRIGAN, D SARANG, M POMMIER, Y TI CELL-DEATH INDUCED BY TOPOISOMERASE INHIBITORS - ROLE OF CALCIUM IN MAMMALIAN-CELLS SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID CYTO-TOXICITY; HEAT-SHOCK; GLUCOCORTICOIDS ACTIVATE; ENDONUCLEASE ACTIVATION; DNA FRAGMENTATION; SUICIDE PROCESS; LEUKEMIA-CELLS; STRAND BREAKS; L1210 CELLS; CAMPTOTHECIN AB Although the stabilization of topoisomerase II cleavable complexes by etoposide (VP-16) has been recognized to be important for cell killing, the lethal events following the formation of cleavable complexes remain to be elucidated. In an attempt to characterize the biochemical requirements for VP-16-induced cytotoxicity, we examined the effects of calcium depletion in Chinese hamster DC3F cells. Four-hour preincubation in calcium-free medium or in complete medium containing 5 mM [ethylenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA) protected against the cytotoxicity of VP-16. Under these same conditions, the VP-16-induced DNA single-strand break frequency in calcium-depleted cells remained similar to that of control cells. Cell-cycle analysis and thymidine pulse incorporation indicated that calcium depletion did not alter DNA synthesis and cell cycle distribution. Drug-induced cytotoxicity was restored progressively within 4-8 hr after calcium-depleted cells were refed with calcium-containing medium. Calcium depletion also protected against the cytotoxicity of camptothecin, hyperthermia and, to a lesser extent, nitrogen mustard and gamma radiation in DC3F cells. Similar results were obtained in human colon carcinoma HT-29 cells. Our results suggest that topoisomerase II-mediated DNA breaks are only potentially lethal and that calcium-dependent cellular processes are required for the cytotoxicity of topoisomerase inhibitors. C1 NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,BLDG 37,RM 5C27,BETHESDA,MD 20892. NR 40 TC 104 Z9 104 U1 2 U2 5 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 JUN 21 PY 1991 VL 42 IS 1 BP 77 EP 85 DI 10.1016/0006-2952(91)90683-V PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FV782 UT WOS:A1991FV78200013 PM 1648924 ER PT J AU OMATA, Y FRIEDMAN, FK AF OMATA, Y FRIEDMAN, FK TI A FLUORESCENCE STUDY OF THE INTERACTIONS OF BENZO[A]PYRENE, CYTOCHROME-P450C AND NADPH CYTOCHROME-P450 REDUCTASE SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID RAT-LIVER CYTOCHROME-P-450; HEPATIC-MICROSOMAL CYTOCHROME-P-450; NADPH-CYTOCHROME-P-450 REDUCTASE; SPIN STATE; MONOCLONAL-ANTIBODIES; ENERGY TRANSFER; PURIFICATION; ASSOCIATION; SUBSTRATE; CATALYSIS AB Fluorescence quenching of benzo[a]pyrene (BP) by cytochrome P450c was used to probe this substrate-enzyme binding interaction. Addition of NADPH-cytochrome P450 reductase, an essential electron carrier during P450 catalysis, resulted in increased quenching and thus strengthened binding of BP to P450c. This shows that the role of reductase extends beyond that of an electron transfer agent to influence substrate binding. Fluorescence titration measurements revealed that reductase and P450c formed a complex with an apparent K(D) of 13.7 +/- 0.9 nM. Reductase had no effect in the presence of an anti-P450c monoclonal antibody which inhibits BP hydroxylation, which suggests that this monoclonal antibody binds P450c near its reductase binding region. C1 NCI,MOLEC CARCINOGENESIS LAB,BLDG 37,ROOM 3E24,BETHESDA,MD 20892. RI Friedman, Fred/D-4208-2016 NR 39 TC 10 Z9 10 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 JUN 21 PY 1991 VL 42 IS 1 BP 97 EP 101 DI 10.1016/0006-2952(91)90686-Y PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FV782 UT WOS:A1991FV78200016 PM 1906275 ER PT J AU ENGBER, TM SUSEL, Z KUO, S GERFEN, CR CHASE, TN AF ENGBER, TM SUSEL, Z KUO, S GERFEN, CR CHASE, TN TI LEVODOPA REPLACEMENT THERAPY ALTERS ENZYME-ACTIVITIES IN STRIATUM AND NEUROPEPTIDE CONTENT IN STRIATAL OUTPUT REGIONS OF 6-HYDROXYDOPAMINE LESIONED RATS SO BRAIN RESEARCH LA English DT Article DE LEVODOPA; 6-HYDROXYDOPAMINE; STRIATUM; DYNORPHIN; ENKEPHALIN; SUBSTANCE-P; GLUTAMIC ACID DECARBOXYLASE; CHOLINE ACETYLTRANSFERASE ID BASAL GANGLIA; PARKINSONS-DISEASE; SUBSTANCE-P; L-DOPA; GLUTAMATE-DECARBOXYLASE; NIGROSTRIATAL PATHWAY; MOTOR FLUCTUATIONS; UNILATERAL LESION; GENE-EXPRESSION; NEURONS AB The effects of striatal dopamine denervation and levodopa replacement therapy on neuronal populations in the rat striatum were assessed by measurement of glutamic acid decarboxylase (GAD) and choline acetyltransferase (CAT) activities in the striatum, dynorphin and substance P concentrations in the substantia nigra, and enkephalin concentration in the globus pallidus. Rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway were treated for 21 days with levodopa (100 mg/kg/day, i.p., with 25 mg/kg benserazide) on either an intermittent (b.i.d.) or continuous (osmotic pump infusion) regimen and sacrificed following a three day drug washout. In saline-treated control rats, striatal GAD activity and globus pallidus enkephalin content were elevated and nigral substance P content was reduced ipsilateral to the 6-OHDA lesion. Intermittent levodopa treatment further increased GAD activity, decreased CAT activity, restored substance P to control levels, markedly increased dynorphin content, and had no effect on enkephalin. In contrast, continuous levodopa elevated globus pallidus enkephalin beyond the levels occurring with denervation, but had no effect on any of the other neurochemical measures. These results indicate that striatal neuronal populations are differentially affected by chronic levodopa therapy and by the continuous or intermittent nature of the treatment regimen. With the exception of substance P, levodopa did not reverse the effects of the 6-OHDA lesion but, rather, either exacerbated the lesion-induced changes (e.g. GAD and enkephalin) or altered neurochemical markers which had been unaffected by the lesion (e.g. CAT and dynorphin). These findings suggest that chronic levodopa treatment may create a new functional state in the striatum which is different from both the normal state and the denervated state and may provide insight into the pathophysiology of the motor response complications which often accompany long-term levodopa therapy in parkinsonian patients. C1 NINCDS,EXPTL THERAPEUT BRANCH,BLDG 10,ROOM 5C103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NR 37 TC 175 Z9 178 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 JUN 21 PY 1991 VL 552 IS 1 BP 113 EP 118 DI 10.1016/0006-8993(91)90667-K PG 6 WC Neurosciences SC Neurosciences & Neurology GA FU388 UT WOS:A1991FU38800017 PM 1717109 ER PT J AU RIUS, RA CHIKUMA, T LOH, YP AF RIUS, RA CHIKUMA, T LOH, YP TI PRENATAL PROCESSING OF PROOPIOMELANOCORTIN IN THE BRAIN AND PITUITARY OF MOUSE EMBRYOS SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE PROOPIOMELANOCORTIN; PRENATAL ONTOGENY; PROHORMONE PROCESSING ID MELANOCYTE-STIMULATING HORMONE; CENTRAL NERVOUS-SYSTEM; ENDORPHIN-DERIVED PEPTIDES; RAT PITUITARY; BETA-ENDORPHIN; INTERMEDIATE LOBE; POSTNATAL-DEVELOPMENT; CONVERTING ENZYME; COMMON PRECURSOR; ACTH ENDORPHIN AB The processing of pro-opiomelanocortin (POMC) to ACTH- (adrenocorticotropin), MSH- (melanotropin) and endorphin-related peptides was studied in mouse embryos with the ultimate aim of determining the role of the POMC-related peptides in early development especially in the CNS. Mouse embryos at gestational days 10.5, 11.5, 12.5 and 14.5 were analyzed for POMC-derived peptides by SDS-PAGE, HPLC and radioimmunoassay using antisera specific for various regions of the prohormone. At embryonic day 10.5 (E 10.5) the prohormone was the major product detected. At E 11.5, POMC was processed to ACTH(1-39), des-acetyl alpha-MSH and beta-endorphin(1-31) and beta-endorphin(1-27). The amounts of these peptides increased at E 12.5, and at E 14.5. At E 14.5, there was a major increase in ACTH(1-39) and beta-endorphin(1-31) peptides. This was attributed to the large increase of corticotrophs in anterior pituitary at this stage. Des-acetyl alpha-MSH levels, however, were similar at E 12.5 and E 14.5 and the peptide was confined mainly to the central nervous system. Gamma-MSH was not detected until E 16.5 in the brain. No alpha-MSH or acetylated beta-endorphin was detected between E 11.5 and E 14.5. Thus in early embryonic development, POMC is processed to des-acetyl alpha-MSH, beta-endorphin(1-31), beta-endorphin(1-27) and gamma-MSH in the brain, and primarily to ACTH(1-39) and beta-endorphin(1-31) in the anterior pituitary. Some differences exist in the forms of POMC-derived peptides found in embryonic versus adult brain and pituitary. The embryonic forms of the peptides may be significant in playing a role during development. C1 NICHHD,DEV NEUROBIOL LAB,CELLULAR NEUROBIOL SECT,BETHESDA,MD 20892. NR 37 TC 13 Z9 13 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD JUN 21 PY 1991 VL 60 IS 2 BP 179 EP 185 DI 10.1016/0165-3806(91)90046-L PG 7 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA FW850 UT WOS:A1991FW85000009 ER PT J AU CUSHMAN, M OH, Y COPELAND, TD OROSZLAN, S SNYDER, SW AF CUSHMAN, M OH, Y COPELAND, TD OROSZLAN, S SNYDER, SW TI DEVELOPMENT OF METHODOLOGY FOR THE SYNTHESIS OF STEREOCHEMICALLY PURE PHE-PSI[CH2N]PRO LINKAGES IN HIV PROTEASE INHIBITORS SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; CHEMICAL SYNTHESIS; POL POLYPROTEINS; GAG; GENE; PURIFICATION; INFECTIVITY; CONVERSION; EXPRESSION; BOND AB One of the strategies currently being pursued for the design of potential HIV protease inhibitors involves the replacement of the cleaved amide bond in a minimum peptide substrate with an aminomethylene unit. A commonly used method for the synthesis of these compounds involves a reductive alkylation of an amine with an aldehyde in the presence of sodium cyanoborohydride under acidic conditions. Accordingly, BOC-phenylalaninal (4) was reacted with the peptide-resin ProIleSer(OBzl)OResin (5) in the presence of acetic acid and sodium cyanoborohydride. The resulting product was found to consist of a mixture of diastereomers, which may result from the fact that the proline residue, which contains a secondary amine, reacts with the aldehyde to form an enamine 9 with loss of chirality at the modified Phe residue. Subsequent reduction of the iminium ion 10 would then result in production of the observed two diastereomers. In order to circumvent this problem, BOCPheProOBzl (12b) was synthesized and the central amide bond was reduced selectively with diborane. Hydrogenolysis of the benzyl protecting group gave BOCPhe-PSI[CH2N]Pro (14a), which was coupled manually to the peptide resin IleSer(OBzl)OResin to give BOCPhe-PSI[CH2N]ProIleSer(OBzl)OResin (6). Subsequent addition of amino acid residues to 6 and cleavage from the resin gave a series of stereochemically defined potential HIV protease inhibitors as single diastereomers. The most potent of these substances was ThrLeuAsnPhe-PSI[CH2N]ProIleSer (1), which displayed an IC50 of 1.1-mu-g/mL (1.4-mu-M) when tested for inhibition of HIV-1 protease. However, the epimer of 1 having the opposite configuration at the reduced Phe residue was inactive. A minimum length of seven amino acid residues appears to be necessary for effective recognition of the inhibitor by the enzyme. Further increase in chain length did not result in greater inhibitory potency. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21701. RP CUSHMAN, M (reprint author), PURDUE UNIV,SCH PHARM & PHARMACAL SCI,DEPT MED CHEM & PHARMACOGNOSY,W LAFAYETTE,IN 47907, USA. NR 23 TC 30 Z9 30 U1 0 U2 1 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 JUN 21 PY 1991 VL 56 IS 13 BP 4161 EP 4167 DI 10.1021/jo00013a017 PG 7 WC Chemistry, Organic SC Chemistry GA FT183 UT WOS:A1991FT18300017 ER PT J AU PELTONEN, K CHENG, SC HILTON, BD LEE, HM CORTEZ, C HARVEY, RG DIPPLE, A AF PELTONEN, K CHENG, SC HILTON, BD LEE, HM CORTEZ, C HARVEY, RG DIPPLE, A TI EFFECT OF BAY REGION METHYL-GROUP ON REACTIONS OF ANTI-BENZ[A]ANTHRACENE 3,4-DIHYDRODIOL 1,2-EPOXIDES WITH DNA SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID EMBRYO CELL-CULTURES; NUCLEOSIDE ADDUCTS; CHEMICAL CARCINOGENESIS; AROMATIC-HYDROCARBONS; METABOLIC-ACTIVATION; DIHYDRODIOL-EPOXIDE; DIOL EPOXIDES; BENZOPYRENE; ARALKYLATION; ACID AB The NMR spectroscopic characterization of seven 7-methylbenz[a]anthracene-deoxyribonucleoside adducts and eight 7,12-dimethylbenz[a]anthracene-deoxyribonucleoside adducts, derived from the reaction of the corresponding anti-dihydrodiol epoxides and deoxyguanylic and deoxyadenylic acids, is described. The epoxide ring is opened by the purine amino groups to yield both cis and trans products from each enantiomer in the racemic dihydrodiol epoxides. Circular dichroism and NMR spectra allow the conformations of the products to be established. Interesting differences between the products from the two hydrocarbons are as follows: the dimethyl derivative is distributed fairly evenly over adenine and guanine residues in DNA, whereas guanine is the principal site for reaction of the monomethyl derivative; the conformation of the tetrahydro ring system is similar in trans products for both hydrocarbons with the hydrogens on C3 and C4 being pseudodiaxial; in cis adducts, these hydrogens are pseudodiaxial for 7,12-dimethylbenz[a]anthracene adducts but pseudodiequatorial for the 7-methylbenz[a]anthracene adducts; in reactions with nucleotides, trans adducts predominate for 7-methylbenz[a]anthracene derivatives but trans and cis adducts form to similar extents for 7,12-dimethylbenz[a]anthracene derivatives. This latter differs substantially from previous findings with other bay region substituted hydrocarbons where cis adducts have been obtained only in low yields. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21701. UNIV CHICAGO,BEN MAY INST,CHICAGO,IL 60637. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,FREDERICK,MD 21701. NR 37 TC 31 Z9 32 U1 0 U2 1 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 JUN 21 PY 1991 VL 56 IS 13 BP 4181 EP 4188 DI 10.1021/jo00013a020 PG 8 WC Chemistry, Organic SC Chemistry GA FT183 UT WOS:A1991FT18300020 ER PT J AU ADAMS, MD KELLEY, JM GOCAYNE, JD DUBNICK, M POLYMEROPOULOS, MH XIAO, H MERRIL, CR WU, A OLDE, B MORENO, RF KERLAVAGE, AR MCCOMBIE, WR VENTER, JC AF ADAMS, MD KELLEY, JM GOCAYNE, JD DUBNICK, M POLYMEROPOULOS, MH XIAO, H MERRIL, CR WU, A OLDE, B MORENO, RF KERLAVAGE, AR MCCOMBIE, WR VENTER, JC TI COMPLEMENTARY-DNA SEQUENCING - EXPRESSED SEQUENCE TAGS AND HUMAN GENOME PROJECT SO SCIENCE LA English DT Article ID CDNA CLONES; DROSOPHILA-MELANOGASTER; MESSENGER-RNA; SUBTRACTION; PROTEIN; LIBRARIES; ENHANCER; CLONING; SYSTEM; SPLIT AB Automated partial DNA sequencing was conducted on more than 600 randomly selected human brain complementary DNA (cDNA) clones to generate expressed sequence tags (ESTs). ESTs have applications in the discovery of new human genes, mapping of the human genome, and identification of coding regions in genomic sequences. Of the sequences generated, 337 represent new genes, including 48 with significant similarity to genes from other organisms, such as a yeast RNA polymerase II subunit; Drosophila kinesin, Notch, and Enhancer of split; and a murine tyrosine kinase receptor. Forty-six ESTs were mapped to chromosomes after amplification by the polymerase chain reaction. This fast approach to cDNA characterization will facilitate the tagging of most human genes in a few years at a fraction of the cost of complete genomic sequencing, provide new genetic markers, and serve as a resource in diverse biological research fields. C1 NINCDS,RECEPTOR BIOCHEM & MOLEC BIOL SECT,BETHESDA,MD 20892. ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,BIOCHEM GENET LAB,WASHINGTON,DC 20032. OI McCombie, W. Richard/0000-0003-1899-0682 NR 34 TC 1616 Z9 1834 U1 15 U2 107 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 21 PY 1991 VL 252 IS 5013 BP 1651 EP 1656 DI 10.1126/science.2047873 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FT114 UT WOS:A1991FT11400035 PM 2047873 ER PT J AU WALDMANN, TA AF WALDMANN, TA TI MONOCLONAL-ANTIBODIES IN DIAGNOSIS AND THERAPY SO SCIENCE LA English DT Article ID ANTIGEN-BINDING SPECIFICITY; INTERLEUKIN-2 RECEPTOR; PSEUDOMONAS EXOTOXIN; EFFECTOR FUNCTIONS; BISPECIFIC ANTIBODY; HUMANIZED ANTIBODY; ESCHERICHIA-COLI; LYMPHOID-CELLS; T-CELLS; IMMUNOTOXIN AB Monoclonal antibodies have been applied clinically to the diagnosis and therapy of an array of human disorders, including cancer and infectious diseases, and have been used for the modulation of immune responses. Effective therapy using unmodified monoclonal antibodies has, however, been elusive. Recently, monoclonal antibody-mediated therapy has been revolutionized by advances such as the definition of cell-surface structures on abnormal cells as targets for effective monoclonal antibody action, genetic engineering to create less immunogenic and more effective monoclonal antibodies, and the arming of such antibodies with toxins or radionuclides to enhance their effector function. RP WALDMANN, TA (reprint author), NCI,METAB BRANCH,BETHESDA,MD 20892, USA. NR 83 TC 281 Z9 286 U1 2 U2 17 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 21 PY 1991 VL 252 IS 5013 BP 1657 EP 1662 DI 10.1126/science.2047874 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FT114 UT WOS:A1991FT11400036 PM 2047874 ER PT J AU MOSS, B AF MOSS, B TI VACCINIA VIRUS - A TOOL FOR RESEARCH AND VACCINE DEVELOPMENT SO SCIENCE LA English DT Article ID TOXIC LYMPHOCYTES-T; BACTERIOPHAGE-T7 RNA-POLYMERASE; DOMINANT SELECTABLE MARKER; POXVIRUS DNA-REPLICATION; THYMIDINE KINASE GENE; HERPES-SIMPLEX VIRUS; RECOMBINANT VACCINIA; MAMMALIAN-CELLS; CLASS-I; EXPRESSION SYSTEM AB Vaccinia virus is no longer needed for smallpox immunization, but now serves as a useful vector for expressing genes within the cytoplasm of eukaryotic cells. As a research tool, recombinant vaccinia viruses are used to synthesize biologically active proteins and analyze structure-function relations, determine the targets of humoral- and cell-mediated immunity, and investigate the immune responses needed for protection against specific infectious diseases. When more data on safety and efficacy are available, recombinant vaccinia and related poxviruses may be candidates for live vaccines and for cancer immunotherapy. RP MOSS, B (reprint author), NIAID,VIRAL DIS LAB,BETHESDA,MD 20892, USA. NR 136 TC 350 Z9 353 U1 4 U2 15 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 21 PY 1991 VL 252 IS 5013 BP 1662 EP 1667 DI 10.1126/science.2047875 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FT114 UT WOS:A1991FT11400037 PM 2047875 ER PT J AU FINBERG, RW WAHL, SM ALLEN, JB SOMAN, G STROM, TB MURPHY, JR NICHOLS, JC AF FINBERG, RW WAHL, SM ALLEN, JB SOMAN, G STROM, TB MURPHY, JR NICHOLS, JC TI SELECTIVE ELIMINATION OF HIV-1-INFECTED CELLS WITH AN INTERLEUKIN-2 RECEPTOR SPECIFIC CYTOTOXIN SO SCIENCE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED CELLS; FUSION PROTEIN; DIPHTHERIA-TOXIN; ENVELOPE GLYCOPROTEIN; LYMPHOCYTES; ACTIVATION; ENTRY; MONOCYTES; CD4 AB Infection by human immunodeficiency virus type 1 (HIV-1) is associated with cellular activation and expression of the interleukin-2 (IL-2) receptor. A genetically engineered fusion toxin, DAB486 IL-2, that contains the enzymatic site and translocation domain of diphtheria toxin and the receptor binding domain of IL-2 specifically kills cells that express high-affinity IL-2 receptors. This toxin selectively eliminated the HIV-1-infected cells from mixed cultures of infected and uninfected cells and inhibited production of viral proteins and infectious virus. Thus, cellular activation antigens present a target for early antiviral intervention. C1 SERAGEN,HOPKINTON,MA 01748. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NIDR,IMMUNOL LAB,BETHESDA,MD 20892. BETH ISRAEL HOSP,CHARLES A DANA RES INST,BOSTON,MA 02215. HARVARD UNIV,BETH ISRAEL HOSP,THORNDIKE LAB,BOSTON,MA 02215. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. BOSTON UNIV MED,BOSTON UNIV HOSP,BOSTON,MA 02118. RP FINBERG, RW (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,INFECT DIS LAB,BOSTON,MA 02115, USA. RI Finberg, Robert/E-3323-2010 NR 28 TC 47 Z9 47 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 JUN 21 PY 1991 VL 252 IS 5013 BP 1703 EP 1705 DI 10.1126/science.1904628 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FT114 UT WOS:A1991FT11400045 PM 1904628 ER PT J AU MARON, BJ AF MARON, BJ TI CARDIAC HYPERTENSION IN ATHLETES - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP MARON, BJ (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 20 PY 1991 VL 324 IS 25 BP 1813 EP 1813 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA FR681 UT WOS:A1991FR68100019 ER PT J AU DAIDONE, MG SILVESTRINI, R DERRICO, A DIFRONZO, G BENINI, E MANCINI, AM GARBISA, S LIOTTA, LA GRIGIONI, WF AF DAIDONE, MG SILVESTRINI, R DERRICO, A DIFRONZO, G BENINI, E MANCINI, AM GARBISA, S LIOTTA, LA GRIGIONI, WF TI LAMININ RECEPTORS, COLLAGENASE-IV AND PROGNOSIS IN NODE-NEGATIVE BREAST CANCERS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID EXTRACELLULAR-MATRIX; ANTIGENS AB In 187 node-negative breast cancers, the expression of laminin receptors and collagenase IV was directly related in 52% of cases, independently of pathological (tumor size and histology) and biological (estrogen receptors and proliferative activity) features. Moreover, the presence of laminin receptors and collagenase IV did not appear to influence tumor proliferative activity, evaluated as H-3-thymidine labelling index. In this case series, relapse-free survival and overall survival at 6 years were significantly affected by tumor size, hormone receptor status and proliferative activity. Conversely, high levels of laminin receptors and collagenase IV failed to influence relapse-free or overall survival, whereas they were strong indicators of local-regional diffusion of the disease. C1 IST NAZL STUDIO & CURA TUMORI,VIA VENEZIAN 1,I-20133 MILAN,ITALY. UNIV BOLOGNA,DEPT PATOL,I-40126 BOLOGNA,ITALY. NCI,PATHOL LAB,BETHESDA,MD 20892. UNIV PADUA,IST ISTOL,I-35100 PADUA,ITALY. RI Daidone, Maria Grazia/E-9232-2017 OI Daidone, Maria Grazia/0000-0002-4786-1321 NR 19 TC 93 Z9 95 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 19 PY 1991 VL 48 IS 4 BP 529 EP 532 DI 10.1002/ijc.2910480409 PG 4 WC Oncology SC Oncology GA FT311 UT WOS:A1991FT31100008 PM 1646175 ER PT J AU KARP, JE BRODER, S AF KARP, JE BRODER, S TI ONCOLOGY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; TRANS RETINOIC ACID; BETA-CAROTENE; GENE; CELL; THERAPY; PRODUCT RP KARP, JE (reprint author), NCI,BETHESDA,MD 20892, USA. NR 16 TC 1 Z9 1 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 JUN 19 PY 1991 VL 265 IS 23 BP 3141 EP 3143 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA FQ770 UT WOS:A1991FQ77000029 PM 2041130 ER PT J AU FRIEDMAN, MA CAIN, DF BRONZERT, D WU, RS AF FRIEDMAN, MA CAIN, DF BRONZERT, D WU, RS TI POOR FUNDING RATES OF CANCER CLINICAL RESEARCH - INTRACTABLE PROBLEM OR SOLVABLE CHALLENGE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article RP FRIEDMAN, MA (reprint author), NCI,CANC THERAPY EVALUAT PROGRAM,EXECUT PL N,RM 742,BETHESDA,MD 20892, USA. NR 2 TC 3 Z9 3 U1 1 U2 4 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 JUN 19 PY 1991 VL 83 IS 12 BP 838 EP 841 DI 10.1093/jnci/83.12.838 PG 4 WC Oncology SC Oncology GA FQ595 UT WOS:A1991FQ59500016 PM 2061943 ER PT J AU BOYD, J PIENTA, KJ GETZENBERG, RH COFFEY, DS BARRETT, JC AF BOYD, J PIENTA, KJ GETZENBERG, RH COFFEY, DS BARRETT, JC TI PRENEOPLASTIC ALTERATIONS IN NUCLEAR MORPHOLOGY THAT ACCOMPANY LOSS OF TUMOR SUPPRESSOR PHENOTYPE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ROUNDNESS FACTOR MEASUREMENT; MULTISTEP CARCINOGENESIS; PROSTATIC-CARCINOMA; MATRIX; CELLS; ORGANIZATION; ASSOCIATION; PROGNOSIS; PROTEINS; GENE AB Alterations of nuclear shape are frequently observed in tumor cells, but the genes controlling these changes and the stage in the neoplastic process at which they occur are unknown. We have studied nuclear shape changes in chemically immortalized, nontumorigenic Syrian hamster embryo cell clones that had either retained (supB+) or lost (supB-) the ability to suppress the tumorigenic phenotype when they were hybridized with a tumor cell line (BP6T). Quantitative morphometric analysis of the nuclei of cells from each of two paris of supB+/supB- variants indicated that the nuclei of supB- cells were significantly more out of round than those of their corresponding supB+ clones. These data indicate that modification of nuclear structure may represent an early, preneoplastic event in multistep chemical carcinogenesis and that loss of a tumor suppressor gene function may regulate alterations in nuclear morphology. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT UROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV HOSP,CTR ONCOL,BALTIMORE,MD 21205. RP BOYD, J (reprint author), NIEHS,MOLEC CARCINOGENESIS LAB,BOX 12233,RES TRIANGLE PK,NC 27709, USA. RI Pienta, Kenneth/E-7679-2015 OI Pienta, Kenneth/0000-0002-4138-2186 FU NCI NIH HHS [CA-15416]; NIDDK NIH HHS [DK 22000] NR 23 TC 34 Z9 35 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 JUN 19 PY 1991 VL 83 IS 12 BP 862 EP 866 DI 10.1093/jnci/83.12.862 PG 5 WC Oncology SC Oncology GA FQ595 UT WOS:A1991FQ59500020 PM 2061946 ER PT J AU SZABO, G TABAKOFF, B HOFFMAN, PL AF SZABO, G TABAKOFF, B HOFFMAN, PL TI COMPARATIVE EFFECTS OF ARGININE VASOPRESSIN, [PGLU4,CYT6]ARGININE VASOPRESSIN-(4-9) AND NERVE GROWTH-FACTOR ON MAINTENANCE OF FUNCTIONAL TOLERANCE TO ETHANOL IN MICE SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Note DE NERVE GROWTH FACTOR; ETHANOL TOLERANCE (EFFECT ON); [PGLU4,CYT6]ARGININE VASOPRESSIN-(4-9); [ARG8]VASOPRESSIN (AVP) ID METABOLITE; RECEPTORS; BRAIN AB Previous work has demonstrated that arginine vasopressin (AVP), acting in the CNS, can maintain functional tolerance to ethanol. We now show that the AVP metabolite peptide, [pGlu4,Cyt6]arginine vasopressin-(4-9), also maintains ethanol tolerance, with a potency similar to that of arginine vasopressin, while nerve growth factor has only a marginal effect. The effects of these peptides on ethanol tolerance correlate with their previously described ability to induce expression of the proto-oncogene, c-fos, in the septum, a putative mechanism underlying peptide effects on neuroadaptive processes. C1 NIAAA,DIV INTRAMURAL CLIN & BIOL RES,12501 WASHINGTON AVE,ROCKVILLE,MD 20852. RI Szabo, Gyula/E-3602-2012 OI Szabo, Gyula/0000-0002-3409-5357 NR 10 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JUN 18 PY 1991 VL 199 IS 1 BP 131 EP 134 DI 10.1016/0014-2999(91)90649-B PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FW013 UT WOS:A1991FW01300021 PM 1909962 ER PT J AU BOYD, DR BUSHMAN, DR DAVIES, RJH DORRITY, MRJ HAMILTON, L JERINA, DM LEVIN, W MCCULLOUGH, JJ MCMORDIE, RAS MALONE, JF PORTER, HP AF BOYD, DR BUSHMAN, DR DAVIES, RJH DORRITY, MRJ HAMILTON, L JERINA, DM LEVIN, W MCCULLOUGH, JJ MCMORDIE, RAS MALONE, JF PORTER, HP TI ABSOLUTE-CONFIGURATIONS OF THE ARENE OXIDE, TRANS-DIHYDRODIOL AND CIS-DIHYDRODIOL PRODUCTS RESULTING FROM METABOLISM OF QUINOLINE AT THE 5,6-BOND SO TETRAHEDRON LETTERS LA English DT Article ID AZA-ARENES AB Trans-6-bromo-5-hydroxy-5,6,7,8-tetrahydroquinoline enantiomers have been resolved via their dibenzoyltartrate salt diastereoisomers. X-ray crystallographic analysis of the (+)-dibenzoyltartrate salt obtained from reaction of (+)-dibenzoyltartaric acid and (-)-trans-6-bromo-5-hydroxy-5,6,7,8-tetrahydro-quinoline, when allied to a stereochemical correlation sequence linking the arene oxide, trans-dihydrodiol and cis-dihydrodiol enantiomers, provides an unequivocal assignment of absolute configuration for these quinoline metabolites. C1 QUEENS UNIV BELFAST,DEPT BIOCHEM,BELFAST BT9 5AG,ANTRIM,NORTH IRELAND. NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. HOFFMANN LA ROCHE INC,DEPT PROT BIOCHEM,NUTLEY,NJ 07110. RP BOYD, DR (reprint author), QUEENS UNIV BELFAST,DEPT CHEM,BELFAST BT9 5AG,ANTRIM,NORTH IRELAND. NR 10 TC 14 Z9 14 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD JUN 17 PY 1991 VL 32 IS 25 BP 2963 EP 2966 DI 10.1016/0040-4039(91)80663-Q PG 4 WC Chemistry, Organic SC Chemistry GA FP135 UT WOS:A1991FP13500036 ER PT J AU MALEKZADEH, S DRESSLER, FA HOEG, JM BREWER, HB ROBERTS, WC AF MALEKZADEH, S DRESSLER, FA HOEG, JM BREWER, HB ROBERTS, WC TI LEFT ATRIAL ENDOCARDIAL LIPID DEPOSITS AND ABSENT TO MINIMAL ARTERIAL LIPID DEPOSITS IN FAMILIAL HYPERCHYLOMICRONEMIA SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Note ID APOLIPOPROTEIN-C-II; HYPERTRIGLYCERIDEMIA; DEFICIENCY C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. RP MALEKZADEH, S (reprint author), NHLBI,PATHOL BRANCH,BETHESDA,MD 20892, USA. NR 12 TC 6 Z9 6 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 15 PY 1991 VL 67 IS 16 BP 1431 EP 1434 DI 10.1016/0002-9149(91)90477-3 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA FR020 UT WOS:A1991FR02000022 PM 2042577 ER PT J AU SIDNEY, S JACOBS, DR HASKELL, WL ARMSTRONG, MA DIMICCO, A OBERMAN, A SAVAGE, PJ SLATTERY, ML STERNFELD, B VANHORN, L AF SIDNEY, S JACOBS, DR HASKELL, WL ARMSTRONG, MA DIMICCO, A OBERMAN, A SAVAGE, PJ SLATTERY, ML STERNFELD, B VANHORN, L TI COMPARISON OF 2 METHODS OF ASSESSING PHYSICAL-ACTIVITY IN THE CORONARY-ARTERY RISK DEVELOPMENT IN YOUNG-ADULTS (CARDIA) STUDY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE CARDIOVASCULAR DISEASE; CORONARY DISEASE; EXERCISE; PHYSICAL FITNESS; QUESTIONNAIRES; RISK FACTORS ID HEART-DISEASE; QUESTIONNAIRE; DESIGN; DEATH AB Physical activity was assessed by questionnaire among 4,956 young blacks and whites aged 18-30 years at the baseline examination (1985-1986) of the Coronary Artery Risk Development in Young Adults (CARDIA) study, a longitudinal study of cardiovascular risk factors. The Physical Activity Recall questionnaire categorized all activity during the previous week, while the Physical Activity History questionnaire quantified participation in 13 specific activities during the previous year. This report compares the two questionnaires with regard to their characterization of the activity levels of the sociodemographic subgroups of the study population and their associations with known physiologic correlates of physical activity. Both questionnaires resulted in the same physical activity patterns for sex (men > women) and age (younger > older) strata. However, the mean Physical Activity History score was higher in white women than in black women, while the Physical Activity Recall scores were nearly equal. The Physical Activity History score was directly related to educational status, and the Physical Activity Recall score was inversely related to educational status. The Physical Activity History score was generally more strongly associated with physiologic variables known to be related to physical activity (e.g., treadmill test duration). Based upon these findings, which may only be appropriate in this age group, it was concluded that the Physical Activity History score was the more valid measure of habitual physical activity in this study group of young adults. C1 UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455. STANFORD UNIV,CTR RES DIS PREVENT,STANFORD,CA 94305. COOPER GREEN HOSP,BIRMINGHAM,AL. UNIV ALABAMA,DIV GEN & PREVENT MED,BEHAV MED UNIT,BIRMINGHAM,AL 35294. NHLBI,BETHESDA,MD 20892. UNIV UTAH,SCH MED,DEPT FAMILY & COMMUNITY MED,SALT LAKE CITY,UT 84112. NORTHWESTERN UNIV,SCH MED,DEPT COMMUNITY HLTH & PREVENT MED,CHICAGO,IL 60611. RP SIDNEY, S (reprint author), KAISER PERMANENTE MED CARE PROGRAM,DIV RES,3451 PIEDMONT AVE,NO CALIF REG,OAKLAND,CA 94611, USA. FU NHLBI NIH HHS [N01-HC-84047, N01-HC-84048, N01-HC-84049] NR 17 TC 134 Z9 134 U1 7 U2 10 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 15 PY 1991 VL 133 IS 12 BP 1231 EP 1245 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA FV266 UT WOS:A1991FV26600004 PM 2063831 ER PT J AU BAIRD, DD WEINBERG, CR ROWLAND, AS AF BAIRD, DD WEINBERG, CR ROWLAND, AS TI REPORTING ERRORS IN TIME-TO-PREGNANCY DATA COLLECTED WITH A SHORT QUESTIONNAIRE - IMPACT ON POWER AND ESTIMATION OF FECUNDABILITY RATIOS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE EPIDEMIOLOGIC METHODS; FERTILITY; INFERTILITY; QUESTIONNAIRES; STATISTICAL POWER ID DELAYED CONCEPTION; CIGARETTE-SMOKING; INFERTILITY; EXPOSURES AB Few tools exist in reproductive epidemiology for studying adverse effects on fertility. Data on time to pregnancy (the number of menstrual cycles required to conceive) can be used to estimate fecundability ratios, a sensitive endpoint for identifying factors associated with reduced fertility. Time-to-pregnancy data can be collected in detailed interviews. The accuracy of data collected on brief, self-administered questionnaires is not known. In a study of occupational exposures to dental assistants conducted in 1987-1988, 523 women provided time-to-pregnancy data both on a short, mailed questionnaire and in a detailed telephone interview. The correlation between the two measures was 0.82. Assuming that the detailed data were accurate, reporting errors in data from the short form were distributed nondifferentially with respect to most covariates of interest in fecundability analyses. Simulation studies were conducted to estimate bias and loss of power from the misclassification. Bias was toward the null. Substantial power was lost in detecting weak exposures. However, exposures that reduce fecundability by 50 percent (equivalent to adding about three cycles to the median time to pregnancy) could still be detected with 80 percent power in samples of about 100 women (half of them exposed to a possible toxin). The authors conclude that time-to-pregnancy data collected with a few self-administered questions can be useful in a variety of epidemiologic studies, including occupational and environmental surveillance programs. C1 NIEHS,DIV BIOMETRY & RISK ASSESSMENT,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709. RP BAIRD, DD (reprint author), NIEHS,DIV BIOMETRY & RISK ASSESSMENT,EPIDEMIOL BRANCH,A3-05,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Baird, Donna/0000-0002-5544-2653 NR 11 TC 79 Z9 80 U1 1 U2 1 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 15 PY 1991 VL 133 IS 12 BP 1282 EP 1290 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA FV266 UT WOS:A1991FV26600009 PM 2063836 ER PT J AU KIANG, JG WU, YY LIN, MC AF KIANG, JG WU, YY LIN, MC TI HEAT-TREATMENT INDUCES AN INCREASE IN INTRACELLULAR CYCLIC-AMP CONTENT IN HUMAN EPIDERMOID-A-431 CELLS SO BIOCHEMICAL JOURNAL LA English DT Article ID INHIBITS NA+/H+ EXCHANGE; NEURO-BLASTOMA CELLS; A-431 CELLS; VITAMIN-E; RAT; HYPERTHERMIA; ADENOSINE; ACCUMULATION; MEMBRANE; CAMP AB The basal level of intracellular cyclic AMP (cAMP(i)) in A-431 cells incubated at 37-degrees-C in Na+-containing Hanks solution is 2086 +/- 139 fmol/10(6) cells. When cells are exposed to 45-degrees-C for 10 min, cAMP(i) increases by 40 +/- 4%, and then returns to basal levels within 30 min. Incubating cells in Ca2+-free or Mg2+-free Hanks solution has no effect on the heat-induced increase in cAMP(i), but the increase is inhibited by acid-loading cells to intracellular pH 7.0 or 6.8. In unheated cells, cAMP(i) increases by 16 +/- 8%, 53 +/- 7%, or 39 +/- 8% when incubated with 3-isobutyl-1-methylxanthine (1 mM), Ro 20-1724 (0.5 mM), or theophylline (1 mM) respectively. However, heat treatment further elevates cAMP(i) in cells treated with phosphodiesterase inhibitors, indicating that heat treatment and phosphodiesterase inhibitors elevate cAMP(i) by a different pathway(s). Heat treatment increases adenylate cyclase activity 2.5-fold. When forskolin (150-mu-M), an adenylate cyclase stimulator, is applied to cells, the basal cAMP(i) increases 28 +/- 6-fold compared with controls. Subsequent heating of these cells lowers cAMP(i) levels to 7.0 +/- 0.5 times that in control cells. This decrease is prevented by pretreatment with pertussis toxin (30 ng/ml, 24 h), suggesting that G-proteins are involved in the process of heat-induced cAMP(i) increase. 2-Deoxy-D-glucose (10 mM), NaN3 (10 mM) and 2,4-dinitrophenol (1 mM) also increase cAMP(i) in A-431 cells. However, application of these metabolic inhibitors to cells before heat treatment does not result in cAMP(i) levels greater than that observed in cells with heat alone. Similar observations are obtained in heat-treated cells previously exposed to adenosine, but not to AMP or ADP. These data are the first to suggest that thermally induced increase in cAMP(i) is due to a combination of activation of adenylate cyclase and G-proteins, and an increase in adenosine owing to ATP breakdown caused by hyperthermia. C1 NIH,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. RP KIANG, JG (reprint author), WALTER REED ARMY MED CTR,DEPT CLIN PHYSIOL,WASHINGTON,DC 20307, USA. NR 42 TC 30 Z9 31 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUN 15 PY 1991 VL 276 BP 683 EP 689 PN 3 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FU093 UT WOS:A1991FU09300017 PM 1648349 ER PT J AU DECLERCQ, E MURASE, J MARQUEZ, VE AF DECLERCQ, E MURASE, J MARQUEZ, VE TI BROAD-SPECTRUM ANTIVIRAL AND CYTOCIDAL ACTIVITY OF CYCLOPENTENYLCYTOSINE, A CARBOCYCLIC NUCLEOSIDE TARGETED AT CTP SYNTHETASE SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID HERPES-SIMPLEX VIRUS; S-ADENOSYLHOMOCYSTEINE HYDROLASE; REPLICATION INVITRO; PYRIMIDINE NUCLEOSIDES; ANALOGS; CYTIDINE; TRIPHOSPHATE; PYRAZOFURIN; INHIBITORS; CYTOSINE AB Cyclopentenylcytosine (Ce-Cyd) is a broad-spectrum antiviral agent active against DNA viruses [herpes (cytomegalo), pox (vaccinia)], (+)RNA viruses [picorna (polio, Coxsackie, rhino), toga (Sindbis, Semliki forest), coronal], (-)RNA viruses [orthomyxo (influenza), paramyxo (parainfluenza, measles), arena (Junin, Tacaribe), rhabdo (vesicular stomatitis)] and (+/-)RNA viruses (reo). Ce-Cyd is a more potent antiviral agent than its saturated counterpart, cyclopentylcytosine (carbodine, C-Cyd). Ce-Cyd also has potent cytocidal activity against a number of tumor cell lines. The putative target enzyme for both the antiviral and antitumor action of Ce-Cyd is assumed to be the CTP synthetase that converts UTP to CTP. In keeping with this hypothesis was the finding that the antiviral and cytocidal effects of Ce-Cyd are readily reversed by Cyd and, to a lesser extent, Urd, but not by other nucleosides such as dThd or dCyd. In contrast, pyrazofurin and 6-azauridine, two nucleoside analogues that are assumed to interfere with OMP decarboxylase, another enzyme involved in the biosynthesis of pyrimidine ribonucleotides, potentiate the cytocidal activity of Ce-Cyd. Ce-Cyd should be further pursued, as such and in combination with OMP decarboxylase inhibitors, for its therapeutic potential in the treatment of both viral and neoplastic diseases. C1 TOYO JOZO CO LTD,RES LABS,MIFU KU,OHITO,SHIZUOKA 41023,JAPAN. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. RP DECLERCQ, E (reprint author), CATHOLIC UNIV LEUVEN,REGA INST MED RES,MINDERBROEDERSSTR 10,B-3000 LOUVAIN,BELGIUM. NR 43 TC 44 Z9 44 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUN 15 PY 1991 VL 41 IS 12 BP 1821 EP 1829 DI 10.1016/0006-2952(91)90120-T PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FN572 UT WOS:A1991FN57200006 PM 1710119 ER PT J AU STEIN, MB MUIRNASH, J UHDE, TW AF STEIN, MB MUIRNASH, J UHDE, TW TI THE QKD INTERVAL IN PANIC DISORDER - AN ASSESSMENT OF END-ORGAN THYROID-HORMONE RESPONSIVITY SO BIOLOGICAL PSYCHIATRY LA English DT Article ID DEPRESSION; TSH; TRH; RESISTANCE AB The QK(d) interval was utilized as a presumptive index of end-organ thyroid hormone effect to test the hypothesis that patients with panic disorder might have abnormal tissue-level responsivity to normal levels of peripherally circulating thyroid hormones. No significant differences in QK(d) intervals were found between 15 patients with panic disorder (230 +/- 50 msec) and 20 normal controls (224 +/- 29 msec) while drug-free. These findings suggest that patients with panic disorder have normal tissue-level responsivity to thyroid hormone. C1 NIMH,BIOL PSYCHIAT BRANCH,ANXIETY & AFFECT DISORDERS SECT,BLDG 10,BETHESDA,MD 20892. NR 19 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 15 PY 1991 VL 29 IS 12 BP 1209 EP 1214 DI 10.1016/0006-3223(91)90328-J PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA FU966 UT WOS:A1991FU96600005 PM 1888802 ER PT J AU DUBOIS, RM BERNAUDIN, JF PAAKKO, P HUBBARD, R TAKAHASHI, H FERRANS, V CRYSTAL, RG AF DUBOIS, RM BERNAUDIN, JF PAAKKO, P HUBBARD, R TAKAHASHI, H FERRANS, V CRYSTAL, RG TI HUMAN NEUTROPHILS EXPRESS THE ALPHA-1-ANTITRYPSIN GENE AND PRODUCE ALPHA-1-ANTITRYPSIN SO BLOOD LA English DT Article ID STIMULATED NEUTROPHILS; PROTEINASE-INHIBITORS; INSITU HYBRIDIZATION; REPLACEMENT THERAPY; PERIPHERAL-BLOOD; RIBONUCLEIC-ACID; HUMAN-LEUKOCYTE; MESSENGER-RNAS; ELASTASE GENE; DEFICIENCY C1 NHLBI,PULM BRANCH,BLDG 10,ROOM 6D03,BETHESDA,MD 20892. NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. HOP HENRI MONDOR,FAC MED,DEPT HISTOL,INSERM,U139,F-94010 CRETEIL,FRANCE. NR 51 TC 57 Z9 57 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1991 VL 77 IS 12 BP 2724 EP 2730 PG 7 WC Hematology SC Hematology GA FR682 UT WOS:A1991FR68200028 PM 2043769 ER PT J AU ODWYER, PJ LACRETA, F ENGSTROM, PF PETER, R TARTAGLIA, L COLE, D LITWIN, S DEVITO, J POPLACK, D DELAP, RJ COMIS, RL AF ODWYER, PJ LACRETA, F ENGSTROM, PF PETER, R TARTAGLIA, L COLE, D LITWIN, S DEVITO, J POPLACK, D DELAP, RJ COMIS, RL TI PHASE-I PHARMACOKINETIC REEVALUATION OF THIOTEPA SO CANCER RESEARCH LA English DT Article ID N,N',N''-TRIETHYLENE THIOPHOSPHORAMIDE; CONTINUOUS-INFUSION; CHEMOTHERAPY; CANCER; THERAPY; PLASMA AB Because the initial evaluation of N,N',N"-triethylenethiophosphoramide (thioTEPA) preceded the standardized approach to the Phase I trials, uncertainty surrounds the recommended dose. Since it has recently been demonstrated that an almost 100-fold increase in dose can be administered in bone marrow transplant regimens, we conducted a Phase I reevaluation of thioTEPA. ThioTEPA was administered i.v. in 50 ml 5% dextrose in water over 10 min. Twenty-seven patients were entered at doses ranging from 30 to 75 mg/m2. The major toxic effect was myelosuppression; thrombocytopenia greater-than-or-equal-to grade 3 occurred in four of seven patients, and leukopenia greater-than-or-equal-to grade 3 in two of seven patients at 75 mg/m2. Among eight patients at 65 mg/m2 only two had greater-than-or-equal-to grade 3 myelosuppression making this the recommended new phase 11 dose for the majority of patients. Moderate (grade 2) easily controlled nausea and vomiting was the only other major side effect. There was no alopecia or mucosal or neurological toxicity. Three partial remissions were observed among nine previously treated ovarian cancer patients. Plasma concentrations of thioTEPA and its major active metabolite triethylenephosphoramide (TEPA) were measured by gas chromatography. The half-life of thioTEPA ranged from 51.6 to 211.8 min, and its pharmacokinetics was dose dependent; total body thioTEPA clearance decreased with increasing dose. The half-life of TEPA was considerably longer than that of the parent compound (3.0 to 21.1 h); as a result, the area under the plasma concentration-time curve (AUC) of TEPA was severalfold greater than that of the parent compound. The ratio of TEPA AUC to thioTEPA AUC decreased with increasing dose, suggesting that formation of TEPA is a saturable step in elimination. The AUC and total body clearance of thioTEPA, but not of TEPA, were closely correlated with neutrophil but not platelet toxicity. C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. AMER CYANAMID CO,LEDERLE LABS,PEARL RIVER,NY 10965. RP ODWYER, PJ (reprint author), FOX CHASE CANC INST,7701 BURHOLME AVE,PHILADELPHIA,PA 19111, USA. FU NCI NIH HHS [CA06927] NR 30 TC 47 Z9 47 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 1991 VL 51 IS 12 BP 3171 EP 3176 PG 6 WC Oncology SC Oncology GA FQ967 UT WOS:A1991FQ96700015 PM 1710167 ER PT J AU YAGI, T TATSUMIMIYAJIMA, J SATO, M KRAEMER, KH TAKEBE, H AF YAGI, T TATSUMIMIYAJIMA, J SATO, M KRAEMER, KH TAKEBE, H TI ANALYSIS OF POINT MUTATIONS IN AN ULTRAVIOLET-IRRADIATED SHUTTLE VECTOR PLASMID PROPAGATED IN CELLS FROM JAPANESE XERODERMA-PIGMENTOSUM PATIENTS IN COMPLEMENTATION GROUP-A AND GROUP-F SO CANCER RESEARCH LA English DT Article ID MAMMALIAN-CELLS; EXCISION REPAIR; DNA-POLYMERASE; SKIN-CANCER; SPECTRUM; MUTAGENESIS; PHOTOPRODUCT; FIBROBLASTS; SPECIFICITY; RADIATION AB To assess the contribution to mutagenesis by human DNA repair defects, a UV-treated shuttle vector plasmid, pZ189, was passed through fibroblasts derived from Japanese xeroderma pigmentosum (XP) patients in two different DNA repair complementation groups (A and F). Patients with XP have clinical and cellular UV hypersensitivity, increased frequency of skin cancer, and defects in DNA repair. The XP DNA repair defects represented by complementation groups A (XP-A) and F (XP-F) are more common in Japan than in Europe or the United States. In comparison to results with DNA repair-proficient human cells (WI38VA13), UV-treated pZ189 passed through the XP-A [XP2OS(SV)] or XP-F [XP2YO(SV)] cells showed fewer surviving plasmids (XP-A less than XP-F) and a higher frequency of mutated plasmids (XP-A greater than XP-F). Base sequence analysis of more than 200 mutated plasmids showed the major type of base substitution mutation to be the G:C --> A:T transition with ali three cell lines. The XP-A and XP-F cells revealed a higher frequency, of G:C --> A:T transitions and a lower frequency of transversions among plasmids with single or tandem mutations and a lower frequency of plasmids with multiple point mutations compared to the normal line. The spectrum of mutations in pZ189 with the XP-A cells was similar to that with the XP-F cells. Seventy-six to 91% of the single base substitution mutations occurred at G:C base pairs in which the 5'-neighboring base of the cytosine was thymine or cytosine. These studies indicate that the DNA repair defects in Japanese XP patients in complementation groups A and F result in different frequencies of plasmid survival and mutagenesis but in similar types of mutagenic abnormalities despite marked differences in clinical features. These results, together with comparable studies from United States patients in XP complementation groups A and D, suggest that G:C --> A:T somatic mutations may be important in the generation of human skin cancer by UV radiation. C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RP YAGI, T (reprint author), KYOTO UNIV,FAC MED,DEPT EXPTL RADIOL,SAKYO KU,KYOTO 606,JAPAN. FU Intramural NIH HHS [Z01 BC004517-31] NR 41 TC 47 Z9 48 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 1991 VL 51 IS 12 BP 3177 EP 3182 PG 6 WC Oncology SC Oncology GA FQ967 UT WOS:A1991FQ96700016 PM 2039995 ER PT J AU HOWARD, RB CHU, H ZELIGMAN, BE MARCELL, T BUNN, PA MCLEMORE, TL MULVIN, DW COWEN, ME JOHNSTON, MR AF HOWARD, RB CHU, H ZELIGMAN, BE MARCELL, T BUNN, PA MCLEMORE, TL MULVIN, DW COWEN, ME JOHNSTON, MR TI IRRADIATED NUDE RAT MODEL FOR ORTHOTOPIC HUMAN LUNG CANCERS SO CANCER RESEARCH LA English DT Article ID HUMAN-TUMOR XENOGRAFTS; CELL-LINES; ATHYMIC RATS; DIFFERENT ORGANS; RENAL CAPSULE; MICE; GROWTH; METASTASIS; TRANSPLANTATION; INTRAPULMONARY AB The development of improved animal models for biological and preclinical studies of human lung cancer is important because lung cancer is the leading cause of cancer death in the United States. To determine whether the Rowett nude rat could serve as an orthotopic (organ-specific) model of this disease, nude rats (CR: NIH-RNU), with and without 500 rads of prior gamma-irradiation, were implanted intrabronchially with 10(7) cultured cells from 3 human lung cancer lines. Without irradiation, the NCI-H460 large-cell undifferentiated carcinoma had a 54% take-rate, whereas the NCI-H125 adenosquamous carcinoma and A549 adenocarcinoma had take-rates of 7 and 33%, respectively; irradiation increased the respective take-rates to 100, 83, and 90%. In irradiated rats, tumor age versus weight measurements showed progressive growth for all three tumors, with growth rates in the order: NCI-H460 > A549 > NCI-H125, requiring approximately 3, 5, and 9 weeks, respectively, for average tumor sizes to exceed 500 mg. The small-cell carcinoma cell line NCI-H345 was implanted only into irradiated rats and resulted in more slowly growing tumors. Histopathological study showed all model tumor types to have histological characteristics consistent with the clinical tumors from which the cell lines were derived. Each tumor type had a different growth pattern, with some of the the A549- and NCI-H125-derived tumors metastasizing to contralateral lung and/or regional lymph nodes. There was no evidence for immunological rejection in irradiated, tumor-bearing rats. Nonirradiated, implanted rats without gross tumor exhibited peribronchiolar mononuclear cell infiltration with or without fibrosis, suggesting prior immunological rejection. The successful orthotopic growth of these 4 human lung cancer cell lines in irradiated nude rats suggests that this model could be useful for biological and preclinical studies of human lung cancer, both in intact rats and via ex vivo perfusion of their tumor-bearing lungs. C1 UNIV COLORADO,HLTH SCI CTR,DEPT SURG,DIV CARDIOTHORAC SURG,CAMPUS BOX C310,4200 E 9TH AVE,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,DEPT PATHOL,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,DEPT RADIOL,DENVER,CO 80262. UNIV COLORADO,CTR CANC,DENVER,CO 80262. UNIV COLORADO,SCH MED,DENVER,CO 80262. NCI,FREDERICK CANC RES FACIL,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,FREDERICK,MD 21701. FU NCI NIH HHS [CA46088, CA46934] NR 32 TC 58 Z9 60 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 1991 VL 51 IS 12 BP 3274 EP 3280 PG 7 WC Oncology SC Oncology GA FQ967 UT WOS:A1991FQ96700031 PM 2040002 ER PT J AU MILES, EW AF MILES, EW TI THE TRYPTOPHAN SYNTHASE ALPHA-2-BETA-2 COMPLEX - CLEAVAGE OF A FLEXIBLE LOOP IN THE ALPHA-SUBUNIT ALTERS ALLOSTERIC PROPERTIES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID YEAST TRIOSEPHOSPHATE ISOMERASE; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; 1.9-A RESOLUTION; HINGE REGION; BETA-SUBUNIT; L-SERINE; IDENTIFICATION; SITE; FRAGMENTS AB This study explores the catalytic and allosteric roles of a flexible loop in tryptophan synthase. Trypsin is known to cleave the tryptophan synthase alpha-2-beta-2 complex in an alpha-subunit loop at Arg-188. Cleavage yields an active "nicked" alpha-2-beta-2 derivative. The new results provide evidence that the alpha-subunit loop serves two important roles: substrate binding and communicating the effects of substrate binding to the beta-subunit. A role for the loop in substrate binding is supported by our finding that addition of a substrate analogue of the alpha-subunit, alpha-glycerol 3-phosphate, decreases the rate of cleavage by trypsin. An allosteric role for the loop is supported by the finding although the native alpha-2-beta-2 complex is strongly inhibited by alpha-glycerol 3-phosphate, the nicked alpha-2-beta-2 Complex is desensitized to this inhibition. The time course of proteolysis in the presence and absence of alpha-glycerol 3-phosphate is followed by sodium dodecyl sulfate-gel electrophoresis and by assays of activity in the presence and absence of alpha-glycerol 3-phosphate. We use spectroscopic measurements of the pyridoxal phosphate-L-tryptophan intermediates at the active site of the beta-subunit to determine the affinity of the native and nicked enzymes for L-tryptophan and alpha-glycerol 3-phosphate. Although cleavage alters the equilibrium distribution of intermediates and reduces the affinity for alpha-glycerol 3-phosphate, it has little effect on the affinity for amino acids bound to the beta-subunit. We conclude that the loop in the alpha-subunit is important for ligand binding and for communicating the effects of ligand binding from the alpha-subunit to the beta-subunit in the alpha-2-beta-2 complex. RP MILES, EW (reprint author), NIDDKD, BIOCHEM PHARMACOL LAB, BLDG 8, RM 225, BETHESDA, MD 20892 USA. NR 24 TC 30 Z9 30 U1 0 U2 0 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 JUN 15 PY 1991 VL 266 IS 17 BP 10715 EP 10718 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FQ774 UT WOS:A1991FQ77400002 PM 1904055 ER PT J AU SAFER, B REINBERG, D JACOB, WF MALDONADO, E CARCAMO, J GARFINKEL, S COHEN, R AF SAFER, B REINBERG, D JACOB, WF MALDONADO, E CARCAMO, J GARFINKEL, S COHEN, R TI INTERACTION OF CAP SEQUENCE SITE BINDING-FACTOR AND TRANSCRIPTION FACTOR IID PRECEDING AND FOLLOWING BINDING TO THE ADENOVIRUS-2 MAJOR LATE PROMOTER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA POLYMERASE-II; TATA-BOX; DNA-BINDING; ACCURATE TRANSCRIPTION; ACTIVATION DOMAIN; INITIATION SITE; PROTEIN; GENE; IDENTIFICATION; SPECIFICITY AB Interaction of cloned yeast, drosophila, and human transcription factor IID (yTFIID, dTFIID, and hTFIID, respectively) with the adenovirus 2 major late promoter (Ad2 MLP) confers a more limited pattern of DNase I protection than that obtained using highly purified native hTFIID (Hahn, S., Buratowski, S., Sharp, P. A. and Guarente, L. (1989) EMBO J. 8, 3379-3382; Van Dyke, M. W., and Sawadogo, M. (1990) Mol. Cell. Biol. 10, 3415-3420; Horikoshi, M., Wang, C. K., Fujii, H., Cromlish, J. A., Weil, P. A., and Roeder, R. G. (1989) Nature 341, 299-303; Peterson, M. G., Tanese, N., Pugh, B. F., and Tjian, R. (1990) Science 248, 1625-1630; Hoey, T., Dynlacht, B. D., Peterson, M. G., Pugh, B. F., and Tjian, R. (1990) Cell 61, 1179-1186). Since the mass of the cloned TFIIDs is considerably less than that of native hTFIID (27-38 kDa versus 120-140 kDa), it is considered likely that native hTFIID exists as a mixed heterodimer. We have recently identified, purified, and characterized a novel transcription factor that binds to the CAP site region (+l to +23) of the Ad2 MLP. This CAP site binding factor, designated CBF, is required for optimal transcriptional activity. We now show that when bound to the Ad2 MLP, yTFIID and CBF interact to generate the extended pattern of DNase I protection conferred by native hTFIID. In addition, bound yTFIID and CBF interact such that the stability of the complex exceeds that of each factor bound alone. We also demonstrate the existence in nuclear extracts of a hTFIID and CBF heterodimer by the electrophoretic mobility shift analysis. CBF, therefore, may represent the first identified member of a large family of gene-specific TFIID-associated factors that are required for the regulated gene-specific expression of TFIID activity. C1 UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT BIOCHEM,PISCATAWAY,NJ 08854. RP SAFER, B (reprint author), NHLBI,PROT & RNA BIOSYNTH SECT,MOLEC HEMATOL LAB,BLDG 10,RM 7D18,BETHESDA,MD 20892, USA. NR 28 TC 19 Z9 19 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 JUN 15 PY 1991 VL 266 IS 17 BP 10989 EP 10994 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FQ774 UT WOS:A1991FQ77400046 PM 2040615 ER PT J AU CALVO, JC RODBARD, D KATKI, A CHERNICK, S YANAGISHITA, M AF CALVO, JC RODBARD, D KATKI, A CHERNICK, S YANAGISHITA, M TI DIFFERENTIATION OF 3T3-L1 PREADIPOCYTES WITH 3-ISOBUTYL-1-METHYLXANTHINE AND DEXAMETHASONE STIMULATES CELL-ASSOCIATED AND SOLUBLE CHONDROITIN 4-SULFATE PROTEOGLYCANS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DERMATAN SULFATE PROTEOGLYCAN; LIPOPROTEIN-LIPASE ACTIVITY; OVARIAN GRANULOSA-CELLS; ADIPOSE CONVERSION; INSULIN REGULATION; MESSENGER-RNA; CORE PROTEIN; FIBRONECTIN; FIBROBLASTS; ADIPOCYTES AB The proteoglycans (cell-associated and culture media) in 3T3-L1 preadipocytes in culture were analyzed before and during differentiation into adipocytes. Cells were metabolically labeled with [S-35]sulfate and [H-3] glucosamine for 24 h and then extracted and analyzed. There was a 1.68 +/- 0.07-fold increase in the S-35 in medium proteoglycan during differentiation, whereas cell-associated proteoglycan radioactivity showed no increase. Analyses of radiolabeled molecules using ion-exchange chromatography, gel filtration, and high performance liquid chromatography after enzymatic or alkaline digestion indicated that all of the S-35 label was recovered as two major species of chondroitin 4-sulfate proteoglycans (CSPG-I and CSPG-II) and 7% as heparan sulfate proteoglycan. CSPG-I has a mass of almost-equal-to 970 kDa with multiple chondroitin sulfate chains (average of 50 kDa each) and a core protein of almost-equal-to 370 kDa including oligosaccharides. CSPG-II has a mass of 140 kDa with one or two chondroitin sulfate chains (average of 68 kDa each) and a core protein of 41 kDa including oligosaccharides. CSPG-I appears to be similar to versican, whereas CSPG-II is similar to decorin and/or biglycan, found in other fibroblastic cells. Cell differentiation was associated with a specific increase in CSPG-I (4.0 +/- 0.2-fold in media and 3.2 +/- 0.5-fold in the cell-associated form). This system should facilitate study of the functional roles of proteoglycans during growth and differentiation. C1 NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892. RP CALVO, JC (reprint author), NIDR,BONE RES BRANCH,BLDG 30,RM 106,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 46 TC 39 Z9 42 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 JUN 15 PY 1991 VL 266 IS 17 BP 11237 EP 11244 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FQ774 UT WOS:A1991FQ77400083 PM 1710220 ER PT J AU GREENBERG, AS EGAN, JJ WEK, SA GARTY, NB BLANCHETTEMACKIE, EJ LONDOS, C AF GREENBERG, AS EGAN, JJ WEK, SA GARTY, NB BLANCHETTEMACKIE, EJ LONDOS, C TI PERILIPIN, A MAJOR HORMONALLY REGULATED ADIPOCYTE-SPECIFIC PHOSPHOPROTEIN ASSOCIATED WITH THE PERIPHERY OF LIPID STORAGE DROPLETS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; GENE-EXPRESSION; ADIPOSE CONVERSION; PHOSPHORYLATION; CELLS; INSULIN; DIFFERENTIATION; METABOLISM; GLUCAGON; OBESITY AB The lipid fraction ("fat cake") of rat epididymal adipocytes contains a prominent phosphoprotein (62 kDa(app) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) that is multiply phosphorylated by cAMP-dependent protein kinase in vivo, at which point it migrates as a 65/67-kDa(app) doublet by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and is by far the most heavily radiolabeled protein in the cell. Western blot analysis of various tissues with immunopurified antibodies purified from antisera raised against the 62-kDa species suggests that the protein is specific for adipocytes. This protein, which we term perilipin, is found in differentiated cultured 3T3-L1 adipocytes, but not in their precursor 3T3-L1 fibroblasts. Immunocytochemical studies with specific antiserum shows that the perilipin is closely associated with the periphery of lipid storage droplets in cultured adipocytes. Given its adipocyte specificity, acute regulation by hormones, and subcellular location, we speculate that perilipin plays a role in the specialized lipid storage function of adipocytes. C1 NIDDKD,MEMBRANE REGULAT SECT,BETHESDA,MD 20892. RP GREENBERG, AS (reprint author), NIDDKD,ENDOCRINOL SECT,CELLULAR & DEV BIOL LAB,BLDG 6,RM B1-16,BETHESDA,MD 20892, USA. NR 39 TC 457 Z9 475 U1 3 U2 17 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 15 PY 1991 VL 266 IS 17 BP 11341 EP 11346 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FQ774 UT WOS:A1991FQ77400097 PM 2040638 ER PT J AU TSAIMORRIS, CH BUCZKO, E WANG, W XIE, XZ DUFAU, ML AF TSAIMORRIS, CH BUCZKO, E WANG, W XIE, XZ DUFAU, ML TI STRUCTURAL ORGANIZATION OF THE RAT LUTEINIZING-HORMONE (LH) RECEPTOR GENE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN THYROTROPIN RECEPTOR; PROTEOGLYCAN CORE PROTEIN; CARTILAGE PROTEOGLYCAN; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; MESSENGER-RNA; CDNA; BINDING; DOMAIN; SEQUENCES AB The luteinizing hormone (LH)/human chorionic gonadotropin (CG) receptor gene was isolated from rat liver genomic libraries and spanned at least 75 kilobase pairs from nucleotide -2057 of the 5'-flanking region to the 3'-noncoding end. The structural configuration of the coding region of the LH receptor gene consists of 11 exons separated by 10 introns that are all located within the putative extracellular domain prior to the first transmembrane region. The 5'-non-coding region contains several potential TATA boxes and SP1 promoter binding sites, as well as six palindromic elements, potential intron/exon splice junctions, and two extended open reading frames in frame with the initiation codon. Primer extension studies indicate the presence of multiple transcriptional initiation sites. Truncated forms of the LH/hCG receptor conform to alternative splicing patterns that are consistent either with the deletion of complete exons or alternate acceptor sites within exons. All splice site junctions correspond to known donor and acceptor consensus sequences. Exons 2-8 approximate the regions of the 14 consecutive 20 amino acid repeated motifs present in the LH, thyrotropin-stimulating hormone, and follicle-stimulating hormone receptor cDNAs, with the exception of a six to eight amino acid shift in each motif. Exons 1, 9, 10, and 11, do not conform to this repetitive intronic motif. These exons, however, contain important structural elements including the conserved cysteines (exons 1, 9, 11), the soybean lectin motif (exon 9), the seven-transmembrane domain with cytoplasmic G protein coupling elements (exon 11), and three putative N-linked glycosylation sites (exon 10), consistent with preservation of significant functional domains within single exons. Exon 10 and the beginning of exon 11 along with the lectin motif are unique to the LH receptor and may be involved in specific association with the hormonal ligand. The homologous regions with other members of the glycoprotein receptor family encoded by exons 2-8, and the common amino acid motif that contains 3 conserved cysteines immediately prior to the first transmembrane region, may be involved in common hormonal interactions and in coupling functions, respectively. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,MOLEC ENDOCRINOL SECT,BLDG 10,BETHESDA,MD 20892. NR 33 TC 126 Z9 128 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 JUN 15 PY 1991 VL 266 IS 17 BP 11355 EP 11359 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FQ774 UT WOS:A1991FQ77400099 PM 2040640 ER PT J AU MUSIL, SY OLSON, CR AF MUSIL, SY OLSON, CR TI CORTICAL AREAS IN THE MEDIAL FRONTAL-LOBE OF THE CAT DELINEATED BY QUANTITATIVE-ANALYSIS OF THALAMIC AFFERENTS SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE PREFRONTAL; PRELIMBIC; INFRALIMBIC; CINGULATE; AREA-6; FRONTAL EYE FIELD ID LATERAL HYPOTHALAMIC AREA; PREFRONTAL CORTEX; HORSERADISH-PEROXIDASE; RHESUS-MONKEY; EFFERENT CONNECTIONS; TOPOGRAPHICAL ORGANIZATION; SUBCORTICAL PROJECTIONS; LIMBIC CORTEX; AMYGDALOID PROJECTIONS; RETROGRADE TRANSPORT AB The aim of these experiments was to establish the number and location of connectionally distinct areas in the medial frontal lobe of the cat. Thirty deposits of distinguishable retrograde tracers were placed at restricted sites spanning the medial frontal lobe in 16 cats. Following each deposit, the number of retrogradely labeled neurons in each of 17 thalamic nuclei was determined. Variations of the thalamic labeling pattern dependent on the location of the cortical tracer deposit were then analyzed by a quantitative procedure. The results indicate that the medial frontal lobe contains three fundamental divisions: the anterior cingulate area, medial area 6, and the medial prefrontal district. The anterior cingulate area derives its strongest thalamic input from the anteromedial nucleus. Medial area 6 is the target of afferents originating in a dorsolateral sector of the mediodorsal nucleus and in the ventroanterior nucleus. Medial prefrontal cortex is heavily innervated by pathways originating in the core of the mediodorsal nucleus and in the principal ventromedial nucleus. Within each major district, thalamic connectional patterns exhibit graded regional variation, with the result that, whereas the connections of the district are not uniform, it is difficult to define further discrete subdivisions. We discuss these results in relation to previously proposed schemes for parcellation of the cat's medial frontal lobe and conclude that the infralimbic and prelimbic areas (areas 25 and 32) of previous systems are best understood not as discrete areas but as ventral and intermediate sectors of a continuous medial prefrontal domain. C1 GEORGE MASON UNIV,DEPT PSYCHOL,FAIRFAX,VA 22030. RP MUSIL, SY (reprint author), NIH,SENSORIMOTOR RES LAB,BLDG 10,RM 10C101,BETHESDA,MD 20892, USA. FU NINDS NIH HHS [R01 NS27287-03] NR 55 TC 16 Z9 16 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUN 15 PY 1991 VL 308 IS 3 BP 457 EP 466 DI 10.1002/cne.903080311 PG 10 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA FR249 UT WOS:A1991FR24900010 PM 1865011 ER PT J AU KORTY, PE BRANDO, C SHEVACH, EM AF KORTY, PE BRANDO, C SHEVACH, EM TI CD59 FUNCTIONS AS A SIGNAL-TRANSDUCING MOLECULE FOR HUMAN T-CELL ACTIVATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN LYMPHOCYTES-T; ANTIGEN RECEPTOR COMPLEX; MONOCLONAL-ANTIBODIES; PERIPHERAL-BLOOD; CO-EXPRESSION; B-CELLS; PROTEIN; GLYCOPROTEIN; DEFINITION; INHIBITION AB The CD59 Ag is a 20-kDa protein that is widely expressed on most leukocytes and RBC, is coupled to the membrane by a phosphatidylinositol-glycan anchoring structure, plays a role in cell interaction between monocytes and T cells, and also functions as an inhibitor of cytolysis by the terminal C components C5b-9. Because this molecule is structurally related to the murine Ly-6 family of Ag, we have investigated whether anti-CD59 mAb might be capable of activating human T lymphocytes in a manner similar to that described for antibodies to the murine Ly-6 Ag. In the presence of the appropriate co-stimulators, mAb to one of the two epitopes on CD59 were capable of inducing both a rise in intracytoplasmic free Ca2+, inositol phosphate production, IL-2 production, and T cell proliferation. Anti-CD59-induced inositol phosphate turnover and IL-2 production were dependent on co-expression of the CD3/TCR complex. CD59-loss mutants of the Jurkat cell line were completely responsive to stimulation by anti-CD3 thereby demonstrating that CD59 does not play a role as a signal transducer downstream from the TCR. Taken together, these results demonstrate that the CD59 Ag can play multiple distinct roles in the regulation of the immune response. C1 NIAID,IMMUNOL LAB,BLDG 10,ROOM 11N315,BETHESDA,MD 20892. NR 32 TC 140 Z9 146 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1991 VL 146 IS 12 BP 4092 EP 4098 PG 7 WC Immunology SC Immunology GA FQ773 UT WOS:A1991FQ77300006 PM 1710238 ER PT J AU DAVIDSON, WF CALKINS, C HUGIN, A GIESE, T HOLMES, KL AF DAVIDSON, WF CALKINS, C HUGIN, A GIESE, T HOLMES, KL TI CYTOKINE SECRETION BY C3H-LPR AND C3H-GLD T-CELLS - HYPERSECRETION OF IFN-GAMMA AND TUMOR-NECROSIS-FACTOR-ALPHA BY STIMULATED CD4+ T-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MRL-LPR/LPR MICE; LPR-LPR MICE; MUTANT-GENE LPR; MP-IPR IPR; MONOCLONAL-ANTIBODY; LYMPHOCYTES-T; IMMUNE INTERFERON; B-CELLS; LYMPHOPROLIFERATIVE DISORDERS; AUTOIMMUNE MICE AB Mice homozygous for lpr and gld develop profound lymphadenopathy characterized by the expansion of two unusual T cell subsets, a predominant Ly5 (B220)+ CD4- CD8- double negative (DN) population and a minor CD4 dull+ Ly-5(B220)+ population. The mechanisms promoting lymphoproliferation are unknown, but one possibility is an abnormality in the production of cytokines that regulate T cell growth. In the present report, unfractionated LN cells and sorted T cell subsets from C3H-lpr, -gld, and -+/+ mice were compared for spontaneous and induced secretion of a spectrum of lymphokines. In addition, CD4+, CD4 dull+ Ly-5(B220)+, and DN T cells were examined for expression of CD3-epsilon, TCR-alpha/beta heterodimers, Ly-6C, and CD44 and for proliferative responses to immobilized anti-TCR mAb and cofactors. These studies revealed that sorted DN T cells did not secrete IL-3, IL-4, IL-5, IL-6, GM-CSF, TNF-alpha, or IFN-gamma spontaneously or after TCR-alpha/beta cross-linking. In contrast, stimulated unfractionated lpr and gld LN cells proliferated strongly and secreted high levels of IFN-gamma and TNF-alpha and low levels of IL-3, IL-4, and IL-6. Despite a 5- to 10-fold deficit in the frequency of CD4+ and CDS+ T cells, cytokine secretion by lpr and gld LN generally exceeded that of +/ + LN. Comparisons of cytokine secretion by stimulated CD4+ T cells revealed that +/+, lpr, and gld CD4+ Ly-5(B220)- T cells proliferated strongly, but only lpr and gld cells produced significant levels of IFN-gamma. The lpr and gld CD4+ T cells also produced higher levels of TNF-alpha and IL-2 than +/+ cells. In contrast to normal CD4+ T cells, lpr and gld CD4+ Ly-5(B220)+ T cells proliferated weakly and did not secrete TNF-alpha, IL-2, or, in most experiments, IFN-gamma after stimulation. Phenotypic studies of T cell subsets revealed that unstimulated lpr and gld CD4+ Ly-5(B220)- T cells express significantly higher levels of CD44 than +/+ CD4+ T cells. In addition, CD4 dull+ Ly-5(B220)+ cells closely resembled DN T cells in size and expression of TCR-alpha/beta, CD3-epsilon, CD44, and Ly-6C. Since elevated CD44 expression is generally associated with T cell activation and only previously activated normal CD4+ T cells produce high levels of IFN-gamma in vitro, our data suggest that lpr and gld CD4+ Ly-5(B220)- T cells contain a higher than normal proportion of primed or memory T cells and thus may be polyclonally activated in vivo. The implications of hypersecretion of lymphokines on the development of lymphoproliferative disease and the possible developmental relationships between CD4+ Ly-5(B220)-, CD4 dull+ Ly-5(B220)+, and DN T cells are discussed. C1 THOMAS JEFFERSON UNIV,DEPT MICROBIOL,PHILADELPHIA,PA 19107. NIAID,IMMUNOPATHOL LAB,BETHESDA,MD 20892. NIAID,BIOL RESOURCES BRANCH,FLOW CYTOMETRY SECT,BETHESDA,MD 20892. RP DAVIDSON, WF (reprint author), NCI,GENET LAB,BLDG 37,ROOM 2B13,BETHESDA,MD 20892, USA. NR 71 TC 64 Z9 64 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 JUN 15 PY 1991 VL 146 IS 12 BP 4138 EP 4148 PG 11 WC Immunology SC Immunology GA FQ773 UT WOS:A1991FQ77300012 PM 1674953 ER PT J AU ALLISON, KC STROBER, W HARRIMAN, GR AF ALLISON, KC STROBER, W HARRIMAN, GR TI INDUCTION OF IL-5 RECEPTORS ON NORMAL B-CELLS BY CROSS-LINKING SURFACE IG WITH ANTI-IG-DEXTRAN SO JOURNAL OF IMMUNOLOGY LA English DT Article ID REPLACING FACTOR TRF; INTERLEUKIN-5 RECEPTOR; DIFFERENTIATION FACTOR; LYMPHOCYTES; IMMUNOGLOBULIN; IDENTIFICATION; PROLIFERATION; LYMPHOKINE; EXPRESSION; POPULATION AB Regulation of lL-5R expression in normal, non-Ly-1 (CD5) B cells was evaluated. Freshly isolated unfractionated spleen B cells express little or no detectable IL-5R. In contrast, B cells stimulated with anti-Ig-dextran conjugates express substantial numbers of IL-5R. Phenotypic analysis of the B cells responding to anti-Ig-dextran, and expressing IL-5R, demonstrates that these cells do not express Ly-1 or Mac-1. Scatchard analysis of B cells stimulated with anti-IgD-dextran reveals two classes of IL-5R: a high affinity receptor with a K(d) Of 17 pM and approximately 300 receptors/cell, and a low affinity receptor with a K(d) of 0.6 nM and approximately 1000 receptors/cell. Peak receptor expression in response to anti-IgD-dextran is seen 72 h after stimulation and with a dose of 10 ng/ml. The induced receptors are functional, because both proliferation and Ig secretion by B cells treated with anti-IgD-dextran are enhanced by IL-5. Other B cell mitogens such as LPS, soluble anti-Ig/IL-4, or phorbol esters/ionomycin are poor inducers of the IL-5R. Finally, not only does LPS fail to induce significant IL-5R expression on spleen B cells, it suppresses both high and low affinity IL-5R expression induced by anti-IgD-dextran. These data indicate that normal, non-Ly-1 B cells are capable of expressing both high and low affinity IL-5R but that receptor expression is critically dependent on the type of stimulus provided to the B cell. A stimulus that produces extensive crosslinking of surface Ig on B cells, i.e., anti-Ig-dextran, is very effective in inducing IL-5R whereas a variety of other B cell mitogens are ineffective. C1 NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BLDG 10,ROOM 11N250,BETHESDA,MD 20892. HOWARD HUGHES MED INST,RES SCHOLARS PROGRAM,BETHESDA,MD 20892. NR 33 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 JUN 15 PY 1991 VL 146 IS 12 BP 4197 EP 4203 PG 7 WC Immunology SC Immunology GA FQ773 UT WOS:A1991FQ77300020 PM 1710244 ER PT J AU KATONA, IM URBAN, JF KANG, SS PAUL, WE FINKELMAN, FD AF KATONA, IM URBAN, JF KANG, SS PAUL, WE FINKELMAN, FD TI IL-4 REQUIREMENTS FOR THE GENERATION OF SECONDARY INVIVO IGE RESPONSES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID STIMULATORY FACTOR-I; MURINE IMMUNE-SYSTEM; B-CELLS; NIPPOSTRONGYLUS-BRASILIENSIS; POLYCLONAL ACTIVATION; MONOCLONAL-ANTIBODY; MAST-CELLS; HUMAN-LYMPHOCYTES; INTERFERON-GAMMA; IMMUNOGLOBULIN AB IL-4 has been shown to induce B lymphocytes to switch from the expression of membrane IgM to the expression of membrane IgE and to be required for the generation of primary polyclonal and secondary Ag-specific IgE responses in mice. To further define the role of IL-4 in the generation of memory IgE responses, we investigated the ability of a combination of anti-IL-4 and anti-IL-4R mAb to block the generation of secondary IgE responses induced by: l) a second infection with the nematode parasites Nippostrongylus brasiliensis or Heligmosomoides polygyrus; or 2) injection of anti-IgD antibody-primed mice with anti-IgE antibody. The latter stimulus was designed to induce intrinsic membrane IgE-expressing B cells to differentiate into IgE-secreting cells. Although the IgE responses induced by a second nematode infection were completely inhibited by the combination of anti-IL-4 and anti-IL-4R mAb, anti-IgE antibody-induced IgE responses in anti-IgD primed mice were not inhibited by these antibodies to a large degree. Additional experiments demonstrated that the anti-IgE antibody-induced memory IgE response was dependent on CD4+ T cells but did not involve the low affinity B cell Fc-epsilon-RII. Taken together, these observations provide evidence that IL-4 is required for virgin B lymphocytes to develop into IgE-expressing cells, but is not required for B cells that express intrinsic membrane IgE to differentiate into IgE-secreting cells in a T-dependent response. Furthermore, these data suggest that secondary IgE responses in the parasite models that we have studied develop from B cells that had not previously switched to the expression of IgE. C1 UNIFORMED SERV UNIV HLTH SCI,F EDWARD HERBERT SCH MED,DEPT MED,BETHESDA,MD 20814. USDA ARS,BELTSVILLE AGR RES CTR,INST LIVESTOCK & POULTRY SCI,HELMINTH DIS LAB,BELTSVILLE,MD 20705. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RP KATONA, IM (reprint author), UNIFORMED SERV UNIV HLTH SCI,F EDWARD HERBERT SCH MED,DEPT PEDIAT,BETHESDA,MD 20814, USA. OI Urban, Joseph/0000-0002-1590-8869 FU NIAID NIH HHS [AI-26150, R01 AI21328] NR 40 TC 60 Z9 60 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 JUN 15 PY 1991 VL 146 IS 12 BP 4215 EP 4221 PG 7 WC Immunology SC Immunology GA FQ773 UT WOS:A1991FQ77300023 PM 1674956 ER PT J AU STEPHAN, V GUO, NH GINSBURG, V SIRAGANIAN, RP AF STEPHAN, V GUO, NH GINSBURG, V SIRAGANIAN, RP TI IMMUNOPRECIPITATION OF MEMBRANE-PROTEINS FROM RAT BASOPHILIC LEUKEMIA-CELLS BY THE ANTIGANGLIOSIDE MONOCLONAL ANTIBODY-AA4 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GANGLIOSIDE-MEDIATED MODULATION; GROWTH-FACTOR RECEPTOR; HIGH-AFFINITY; HISTAMINE-RELEASE; IGE RECEPTOR; TYROSINE PHOSPHORYLATION; SIGNAL TRANSDUCTION; IMMUNOGLOBULIN-E; BINDING; ANTIBODIES AB In previous studies, mAb AA4 inhibited IgE binding, induced rapid morphologic changes, and blocked histamine release in rat basophilic leukemia (RBL-2H3) cells. It bound to two novel derivatives of ganglioside G(Dlb) (Ag I and Ag II) that appear to be present only in rat mast cells. The present study demonstrates the importance of gangliosides Ag I and Ag II for binding of mAb AA4 to intact cells. We also investigated the presence of gangliosides Ag I and Ag 11 and proteins immunoprecipitated with mAb AA4 in the parental and four variant cell lines. In comparison with the parental RBL-2H3, two variant cell lines had very low (0.5% and 2.0%) and two others had intermediate levels (9% and 18%) of I-125-AA4 binding. mAb AA4 inhibited I-125-IgE binding to the parental RBL-2H3 cells and to only one variant with intermediate amounts of gangliosides Ag I and Ag II. Therefore, there are variations in the proximity of these gangliosides to the high affinity IgE receptor (Fc-epsilon-RI) among different cell lines. mAb AA4 immunoprecipitated proteins of 50 to 60, 120, and 135 kDa from I-125-surface labeled cells. These were different from the subunits of Fc-epsilon-RI. The amount of gangliosides Ag I and Ag II in cell extracts correlated with the number of mAb AA4 binding sites on the cell surface and with the quantity of proteins precipitated from the different cell lines. Thus, these membrane proteins appear to be associated with gangliosides Ag I and Ag II. The binding of mAb AA4 to the surface gangliosides could induce intracellular changes through transmembrane signaling by these proteins. C1 NIDR,IMMUNOL LAB,CLIN IMMUNOL SECT,BETHESDA,MD 20892. NIDDKD,STRUCT BIOL LAB,BETHESDA,MD 20892. NR 25 TC 12 Z9 12 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 JUN 15 PY 1991 VL 146 IS 12 BP 4271 EP 4277 PG 7 WC Immunology SC Immunology GA FQ773 UT WOS:A1991FQ77300031 PM 1828263 ER PT J AU PINCUS, SH COLE, RL HERSH, EM LAKE, D MASUHO, Y DURDA, PJ MCCLURE, J AF PINCUS, SH COLE, RL HERSH, EM LAKE, D MASUHO, Y DURDA, PJ MCCLURE, J TI INVITRO EFFICACY OF ANTI-HIV IMMUNOTOXINS TARGETED BY VARIOUS ANTIBODIES TO THE ENVELOPE PROTEIN SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RICIN-A-CHAIN; EXOTOXIN HYBRID PROTEIN; INFECTED-CELLS; REVERSE-TRANSCRIPTASE; MONOCLONAL-ANTIBODIES; TYPE-1 GP120; T-CELLS; EXPRESSION; SURFACE AB Six different anti-HIV envelope antibodies and one irrelevant control antibody were coupled to ricin A chain and tested for their efficacy in inhibiting HIV tissue culture infections. The anti-HIV antibodies consisted of five monoclonals, three of murine and two of human origin, and one polyclonal preparation prepared by affinity purifying pooled serum antibodies from HIV-infected humans on rgp160. The binding specificity of the antibodies was defined by ELISA by using recombinant envelope proteins and synthetic peptides, and by flow cytometry on HIV-infected cells. The in vitro efficacy of the antibodies was tested by the abilities of the immunotoxins to inhibit protein synthesis in persistently infected cell lines and by their abilities to inhibit HIV production during both acute and persistent infection as measured with an HIV-specific focal immunoassay. The immunotoxins were tested against a panel of distinctly different HIV isolates. The results indicate the following: 1) A mAb to the immunodominant neutralizing loop was highly effective against homologous strains of HIV, but had no activity against heterologous HIV. 2) The efficacy of anti-gp41 mAb varied depending upon the epitope recognized and possibly the affinity of binding to gp41. 3) The polyclonal human anti-gp160 antibodies produced the immunotoxin with the broadest specificity for different HIV strains and the greatest specific activity. This is related to the polyclonal nature of the preparation rather than an increase in relative avidity of the antibody. 4) Activity of an immunotoxin is not a direct function of the binding of the antibody to the surface of infected cells. 5) The ability of an immunotoxin to halt the spread of infection through a tissue culture cell population is dependent upon the ability of the antibody to neutralize the virus as well as the activity of the toxin. Our data suggest that efficacious immunotoxins for the treatment of AIDS may be made with polyclonal anti-envelope antibodies derived from the serum of patients who have been infected with HIV or with appropriately chosen anti-gp4l antibodies. C1 UNIV ARIZONA,DEPT MED,TUCSON,AZ 85724. TEIJIN INST BIOMED RES,HINO,TOKYO 191,JAPAN. DUPONT CO,N BILLERICA,MA 01862. ONCOGEN CORP,SEATTLE,WA 98121. RP PINCUS, SH (reprint author), NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT,HAMILTON,MT 59840, USA. FU NIAID NIH HHS [R01 AI 27689-01] NR 35 TC 43 Z9 43 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 JUN 15 PY 1991 VL 146 IS 12 BP 4315 EP 4324 PG 10 WC Immunology SC Immunology GA FQ773 UT WOS:A1991FQ77300038 PM 1710247 ER PT J AU HOLE, NJK HARINDRANATH, N YOUNGCOOPER, GO GARCIA, R MAGE, RG AF HOLE, NJK HARINDRANATH, N YOUNGCOOPER, GO GARCIA, R MAGE, RG TI IDENTIFICATION OF ENHANCER SEQUENCES 3' OF THE RABBIT IG KAPPA-L-CHAIN LOCI SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL-SPECIFIC ENHANCER; J-C LOCUS; GENE-EXPRESSION; LIGHT CHAIN; IMMUNOGLOBULIN GENE; TRANSGENIC MICE; STABLE INTEGRATION; BASILEA RABBITS; MESSENGER-RNA; INTRONIC MAR AB The rabbit is useful for studies of Ig L chain gene expression because of a great disparity in expression of two isotypic forms of the kappa-L chain. Normally, K1 is expressed at high levels and K2 is almost silent; expression of K2 increases in mutant or experimentally allotype-suppressed animals. The reasons for the preferential utilization of the K1 isotype have not been fully elucidated. We were interested in looking for second enhancers 3' of the C-kappa genes because the absence of a 3' enhancer in the K2 locus could explain the preferential utilization of the K1 isotype. However, we found a strong region of enhancer activity about 7 kb downstream of the C-kappa-2 gene. Sequences in this region are highly conserved between rabbit, man, and mouse. There also appears to be a homologous 3' enhancer region in the rabbit K1 locus. We also confirmed earlier reports that the rabbit K1 intron enhancer is inactive in transient transfections into mouse B cells but find that the same construct has low but significant activity in a human B cell line. In a comparable construct the K2 intron enhancer is without activity suggesting possible differential activity of the intronic enhancers. C1 NIAID,IMMUNOL LAB,MOLEC IMMUNOGENET SECT,BLDG 10,11-N-311,BETHESDA,MD 20892. NR 48 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 JUN 15 PY 1991 VL 146 IS 12 BP 4377 EP 4384 PG 8 WC Immunology SC Immunology GA FQ773 UT WOS:A1991FQ77300046 PM 1904082 ER PT J AU ROBINSON, MA AF ROBINSON, MA TI THE HUMAN T-CELL RECEPTOR BETA-CHAIN GENE-COMPLEX CONTAINS AT LEAST 57 VARIABLE GENE SEGMENTS - IDENTIFICATION OF 6-V-BETA-GENES IN 4 NEW GENE FAMILIES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID REGION GENES; ANTIGEN RECEPTOR; CYTOCHROME-C; ALPHA-CHAIN; DIVERSITY; DNA; POLYMORPHISM; POLYMERASE; SPECIFICITY; REPERTOIRE AB The human TCR beta-chain gene complex includes at least 57 variable (V) gene segments, a number estimated using a combination of Southern blots of conventional and pulsed field gels, sequence analysis of cDNA clones, and from the analysis of genomic cosmid and phage clones. This number includes six TCR beta-chain V genes in four new families identified here by sequence analysis of clones derived from a human TCR beta-chain specific cDNA library. Comparison of the sequences of the new V-beta genes with previously reported V-beta sequences reveals predicted similarities but less than 75% nucleic acid identity that establishes them as new V-beta families. One of the new V-beta gene families includes three genes and the other three are single member families. Identification of these six new V-beta genes falling into four V-beta families brings the total number of transcribed human V-beta families to 24 and makes it possible to refine the estimate of the total number of human TCR V-beta genes to 57. RP ROBINSON, MA (reprint author), NIAID,IMMUNOGENET LAB,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. NR 32 TC 119 Z9 120 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 JUN 15 PY 1991 VL 146 IS 12 BP 4392 EP 4397 PG 6 WC Immunology SC Immunology GA FQ773 UT WOS:A1991FQ77300048 PM 1674957 ER PT J AU FILLINGKATZ, MR CHOYKE, PL AF FILLINGKATZ, MR CHOYKE, PL TI GENETIC MECHANISMS IN VONHIPPELLINDAU DISEASE SO LANCET LA English DT Letter ID LINDAU DISEASE C1 NIH,WARREN G MAGNUSSEN CLIN CTR,DEPT RADIOL,BETHESDA,MD 20892. RP FILLINGKATZ, MR (reprint author), NIAAA,GENET STUDIES SECT,BETHESDA,MD 20892, USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUN 15 PY 1991 VL 337 IS 8755 BP 1477 EP 1478 DI 10.1016/0140-6736(91)93167-8 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA FR060 UT WOS:A1991FR06000038 ER PT J AU BULDYREV, SV HAVLIN, S KERTESZ, J STANLEY, HE VICSEK, T AF BULDYREV, SV HAVLIN, S KERTESZ, J STANLEY, HE VICSEK, T TI BALLISTIC DEPOSITION WITH POWER-LAW NOISE - A VARIANT OF THE ZHANG MODEL SO PHYSICAL REVIEW A LA English DT Note ID CORRELATED NOISE; GROWTH; INTERFACES; SURFACES AB We study a variant of the Zhang model [Y.-C. Zhang, J. Phys. (Paris) 51, 2113 (1990)], ballistic deposition of rods with the length l of the rods being chosen from a power-law distribution P(l) approximately l-1-mu. Unlike in the Zhang model, the site at which each rod is dropped is chosen randomly. We confirm that the growth of the rms surface width w with length scale L and time t is described by the scaling relation w(L,t) = L-alpha-w(t/L-alpha/beta), and we calculate the values of the surface-roughening exponents-alpha and beta. We find evidence supporting the possibility of a critical value mu-c almost-equal-to 5 for d = 1, with alpha = 1/2 and beta = 1/3 for mu > mu-c, while for mu < mu-c, alpha and beta vary smoothly, attaining the values alpha = beta = 1 for mu = 2. C1 BOSTON UNIV,DEPT PHYS,BOSTON,MA 02215. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. INST TECH PHYS,H-1325 BUDAPEST,HUNGARY. RP BULDYREV, SV (reprint author), BOSTON UNIV,CTR POLYMER STUDIES,BOSTON,MA 02215, USA. RI Vicsek, Tamas/A-3305-2009; Kertesz, Janos/B-3411-2012; Buldyrev, Sergey/I-3933-2015 NR 26 TC 31 Z9 31 U1 0 U2 2 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1050-2947 J9 PHYS REV A JI Phys. Rev. A PD JUN 15 PY 1991 VL 43 IS 12 BP 7113 EP 7116 DI 10.1103/PhysRevA.43.7113 PG 4 WC Optics; Physics, Atomic, Molecular & Chemical SC Optics; Physics GA FU846 UT WOS:A1991FU84600082 ER PT J AU MOGI, M GUROFF, G AF MOGI, M GUROFF, G TI OKADAIC ACID STIMULATES THE ACTIVITY OF THE NERVE GROWTH FACTOR-SENSITIVE S6 KINASE OF PC12 CELLS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROTEIN-KINASE; TUMOR PROMOTER; INSULIN RP MOGI, M (reprint author), NICHHD,GROWTH FACTORS SECT,BETHESDA,MD 20892, USA. NR 11 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 14 PY 1991 VL 177 IS 2 BP 624 EP 629 DI 10.1016/0006-291X(91)91834-Y PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FQ805 UT WOS:A1991FQ80500005 PM 1646606 ER PT J AU HORN, VJ BAUM, BJ AMBUDKAR, IS AF HORN, VJ BAUM, BJ AMBUDKAR, IS TI MUSCARINIC RECEPTOR ANTAGONIST EFFECTS IN PAROTID ACINI AND M1-CHO CELLS - EVIDENCE OF G-PROTEIN INVOLVEMENT SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID RECIPROCAL MODULATION; GUANINE-NUCLEOTIDES; ADENYLATE-CYCLASE; PHOSPHOLIPASE-C; BINDING; AGONIST; ACTIVATION; STIMULATION; MEMBRANE; ALUMINUM RP HORN, VJ (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892, USA. NR 29 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 14 PY 1991 VL 177 IS 2 BP 784 EP 789 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FQ805 UT WOS:A1991FQ80500028 PM 1904723 ER PT J AU MIKI, H OHMORI, M PERANTONI, AO ENOMOTO, T AF MIKI, H OHMORI, M PERANTONI, AO ENOMOTO, T TI K-RAS ACTIVATION IN GASTRIC EPITHELIAL TUMORS IN JAPANESE SO CANCER LETTERS LA English DT Article DE GASTRIC TUMOR; K-RAS; POINT MUTATION ID POLYMERASE CHAIN-REACTION; HUMAN STOMACH-CANCER; GENE-MUTATIONS; POINT MUTATION; ONCOGENES; CODON-13; COLON AB Point mutation in codons 12, 13 and 61 of the K-ras oncogene in gastric epithelial tumors were investigated by polymerase chain reaction from sections of formalin-fixed, paraffin-embedded tissue followed by dot-blot hybridization with mutation-specific oligonucleotide probes. Point mutations were found specifically in four of 20 tumors of intestinal histological subtype; GGT to GAT in three cases and to GTT in one case, all in codon 12 of K-ras. These mutations were also confirmed by direct sequencing. In contrast, none of 11 diffuse-type tumors showed K-ras point mutations. While K-ras point mutations may not be frequent events in gastric tumorigenesis, the similarity of the intestinal-type gastric tumors and colorectal tumors for K-ras point mutations as well as the association of mutations in K-ras with a particular gastric tumor histology implicates K-ras activation in the development of these tumors. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21701. RP MIKI, H (reprint author), KAGAWA MED SCH,DEPT PATHOL,MIKI,KAGAWA 76107,JAPAN. NR 27 TC 30 Z9 31 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JUN 14 PY 1991 VL 58 IS 1-2 BP 107 EP 113 DI 10.1016/0304-3835(91)90031-C PG 7 WC Oncology SC Oncology GA FT863 UT WOS:A1991FT86300015 PM 2049776 ER PT J AU GINSBURG, E VONDERHAAR, BK AF GINSBURG, E VONDERHAAR, BK TI STIMULATION OF GROWTH OF HUMAN BREAST-CANCER CELLS (T47D) BY PLATELET DERIVED GROWTH-FACTOR SO CANCER LETTERS LA English DT Article DE BREAST CELLS; T47D; PLATELET DERIVED GROWTH FACTOR; MCF-7 ID FACTOR-BETA; PDGF; BINDING; SERUM; SECRETION; RECEPTOR; PHOSPHOLIPASE-A2; PURIFICATION; ANTIBODIES; EXPRESSION AB The human breast cancer cell lines T47D and MCF-7, respond to the mitogenic action of exogenously added PDGF with a 2 - 3-fold increase in cell number. The maximal response was obtained at a concentration of 1.25 half maximal units/ml (125 ng/ml). PDGF-AA was even more effective than PDGF-AB while PDGF-BB was without effect. The growth-enhancing activity of PDGF was completely abolished by Fab fragments of anti PDGF. Within 7 min of addition of PDGF to cultures of T47D cells, specific phosphorylation of a 65-kDa protein was observed. T47D cells contain specific receptors for PDGF with approximately 4-7 x 10(4) sites (kDa of 3-4 x 10(-10) M) per cell. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BLDG 10,ROOM 5B56,BETHESDA,MD 20892. NR 29 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JUN 14 PY 1991 VL 58 IS 1-2 BP 137 EP 144 DI 10.1016/0304-3835(91)90036-H PG 8 WC Oncology SC Oncology GA FT863 UT WOS:A1991FT86300020 PM 1710949 ER PT J AU BEPLER, G JAQUES, G OIE, HK GAZDAR, AF AF BEPLER, G JAQUES, G OIE, HK GAZDAR, AF TI HUMAN CHORIONIC-GONADOTROPIN AND RELATED GLYCOPROTEIN HORMONES IN LUNG-CANCER CELL-LINES SO CANCER LETTERS LA English DT Article DE HUMAN CHORIONIC GONADOTROPIN; NON-SMALL-CELL LUNG CANCER; SMALL CELL LUNG CARCINOMA; CARCINOID OF THE LUNG ID ALPHA-SUBUNIT; DIFFERENTIATION; CARCINOMA; MARKERS; GROWTH; IMMUNOPEROXIDASE; ENDOCRINE; TUMORS AB Twenty-five non-small cell lung cancer (NSCLC), 42 small cell lung carcinoma (SCLC), one extrapulmonary small cell carcinoma, 4 carcinoid, and 13 non-lung cancer cell lines were analyzed for human chorionic gonadotropin (HCG) and related glycoprotein hormones. HCG or its subunits were present in 72% of NSCLC, 10% of SCLC, one extrapulmonary small cell carcinoma, 3/4 carcinoids and 2/13 non-lung cancer cell lines. Related glycoprotein hormones were undetectable. These data indicate a frequent production of HCG or its subunits by NSCLC cell lines and cell lines from tumors with carcinoid features. They confirm the clinical inclusion of carcinoids under the broad category of NSCLC rather than SCLC despite their neuroendocrine features. Clinicians should not assume that undifferentiated NSCLC with HCG production represent germ cell tumors. C1 NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20892. UNIV MARBURG,MED CTR,DEPT MED,W-3550 MARBURG,GERMANY. NR 22 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JUN 14 PY 1991 VL 58 IS 1-2 BP 145 EP 150 DI 10.1016/0304-3835(91)90037-I PG 6 WC Oncology SC Oncology GA FT863 UT WOS:A1991FT86300021 PM 1646686 ER PT J AU BAKER, TA MIZUUCHI, M MIZUUCHI, K AF BAKER, TA MIZUUCHI, M MIZUUCHI, K TI MUB PROTEIN ALLOSTERICALLY ACTIVATES STRAND TRANSFER BY THE TRANSPOSASE OF PHAGE-MU SO CELL LA English DT Article ID BACTERIOPHAGE-MU; B-PROTEIN; TARGET IMMUNITY; DNA; MECHANISM; ENDS; PURIFICATION; INTEGRATION; INVITRO; TN10 AB The MuA and MuB proteins collaborate to mediate efficient transposition of the phage Mu genome into many DNA target sites. MuA (the transposase) carries out all the DNA cleavage and joining steps. MuB stimulates strand transfer by activating the MuA-donor DNA complex through direct protein-protein contact. The C-terminal domain of MuA is required for this MuA-MuB interaction. Activation of strand transfer occurs irrespective of whether MuB is bound to target DNA. When high levels of MuA generate a pool of free MuB (not bound to DNA) or when chemical modification of MuB impairs its ability to bind DNA, MuB still stimulates strand transfer. However, under these conditions, intramolecular target sites are used exclusively because of their close proximity to the MuA-MuB-donor DNA complex. RP BAKER, TA (reprint author), NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 30 TC 92 Z9 93 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUN 14 PY 1991 VL 65 IS 6 BP 1003 EP 1013 DI 10.1016/0092-8674(91)90552-A PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FR047 UT WOS:A1991FR04700011 PM 1646076 ER PT J AU PARSEGIAN, VA RAND, RP FULLER, NL AF PARSEGIAN, VA RAND, RP FULLER, NL TI DIRECT OSMOTIC-STRESS MEASUREMENTS OF HYDRATION AND ELECTROSTATIC DOUBLE-LAYER FORCES BETWEEN BILAYERS OF DOUBLE-CHAINED AMMONIUM ACETATE SURFACTANTS SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID AQUEOUS-ELECTROLYTE SOLUTIONS; CHARGED PHOSPHOLIPID-BILAYERS; LECITHIN BILAYERS; PHOSPHATIDYLCHOLINE BILAYERS; REPULSION; SURFACES; DEFORMATION; MEMBRANES AB Using the osmotic stress method, we have directly measured forces between bilayers of the long-chain substituted amine dihexadecyldimethylammonium acetate in 5-500 mM acetate solutions. Including this molecule with such a small polar group, every lipid system yet investigated shows hydration repulsion at short range. For these frozen hydrocarbon chain bilayers brought together in solutions of low salt concentration down to separations of 15-17 angstrom, the repulsive force is well described by electrostatic double-layer interactions. Because the layers are stiff, there is no amplifying action of undulatory thermal fluctuations. Below 15-17-angstrom separations, there is a clear break and a transition to a region with an exponentially varying force with a 2.7-3.3-angstrom decay constant. No oscillatory forces are seen. That these shorter range interactions were not seen in previous measurements with lipids adsorbed onto the crossed cylindrical mica sheets of a "surface force apparatus" (Pashley, R. M.; McGuiggan, P. M.; Ninham, B. W.; Brady, J.; Evans, D. F. J. Phys. Chem. 1986, 90, 1637) can be explained by the opposite bilayer curvatures enforced in that system and the stress limitations caused by mica bending. Force measurements between oppositely curved surfaces, even of dimensions of centimeters in radius, systematically smother short-range and emphasize long-range forces. Therefore critical examination of forces between contact and 20-angstrom separations should, where possible, be made between parallel rather than oppositely curved surfaces. C1 BROCK UNIV,ST CATHARINES L2S 3A1,ONTARIO,CANADA. NIH,BETHESDA,MD 20892. NR 37 TC 71 Z9 72 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3654 J9 J PHYS CHEM-US JI J. Phys. Chem. PD JUN 13 PY 1991 VL 95 IS 12 BP 4777 EP 4782 DI 10.1021/j100165a034 PG 6 WC Chemistry, Physical SC Chemistry GA FR756 UT WOS:A1991FR75600034 ER PT J AU PACKER, C GILBERT, DA PUSEY, AE OBRIEN, SJ AF PACKER, C GILBERT, DA PUSEY, AE OBRIEN, SJ TI A MOLECULAR GENETIC-ANALYSIS OF KINSHIP AND COOPERATION IN AFRICAN LIONS SO NATURE LA English DT Article ID DNA; RELATEDNESS; COALITIONS; PATERNITY AB AFRICAN lions live in complex social groups and show extensive cooperative behaviour 1-10. Here we describe a new application of DNA fingerprinting that unequivocally demonstrates the kinship structure of lion 'prides': female companions are always closely related, male companions are either closely related or unrelated, and mating partners are usually unrelated. The variability in relatedness among male coalition partners provides an important opportunity to test for the effects of kinship on cooperative behaviour 11. Paternity analysis reveals that male reproductive success becomes increasingly skewed as coalition size increases, and the tendency to form coalitions with non-relatives drops sharply with increasing coalition size. Thus males only act as non-reproductive 'helpers' in coalitions composed of close relatives. C1 WR GRACE & CO CONN,WASHINGTON RES CTR,DEPT BIOMOLEC RES,COLUMBIA,CT. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. RP PACKER, C (reprint author), UNIV MINNESOTA,DEPT ECOL EVOLUT & BEHAV,MINNEAPOLIS,MN 55455, USA. NR 27 TC 319 Z9 326 U1 8 U2 78 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD JUN 13 PY 1991 VL 351 IS 6327 BP 562 EP 565 DI 10.1038/351562a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FR034 UT WOS:A1991FR03400057 ER PT J AU WHITE, RE SCHONBRUNN, A ARMSTRONG, DL AF WHITE, RE SCHONBRUNN, A ARMSTRONG, DL TI SOMATOSTATIN STIMULATES CA2+-ACTIVATED K+ CHANNELS THROUGH PROTEIN DEPHOSPHORYLATION SO NATURE LA English DT Article ID PITUITARY CELL-LINE; VASOACTIVE INTESTINAL PEPTIDE; AMP-INDEPENDENT ACTIONS; INTRACELLULAR FREE CALCIUM; PERTUSSIS TOXIN BLOCKS; CYCLIC-AMP; TUMOR-CELLS; GH3 CELLS; POTASSIUM CONDUCTANCE; PROLACTIN SECRETION AB THE neuropeptide somatostatin inhibits secretion from electrically excitable cells in the pituitary, pancreas, gut and brain 1. In mammalian pituitary tumour cells somatostatin inhibits secretion through two distinct pertussis toxin-sensitive mechanisms 2-5. One involves inhibition of adenylyl cyclase 6, the other an unidentified cyclic AMP-independent mechanism that reduces Ca2+ influx 7,8 by increasing membrane conductance to potassium 9,10. Here we demonstrate that the predominant electrophysiological effect of somatostatin on metabolically intact pituitary tumour cells is a large, sustained increase in the activity of the large-conductance Ca2+- and voltage-activated K+ channels (BK). This action of somatostatin does not involve direct effects of Ca2+, cAMP or G proteins on the channels. Our results indicate instead that somatostatin stimulates BK channel activity through protein dephosphorylation. C1 NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709. UNIV TEXAS,SCH MED,DEPT PHARMACOL,HOUSTON,TX 77225. NR 39 TC 247 Z9 248 U1 0 U2 6 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD JUN 13 PY 1991 VL 351 IS 6327 BP 570 EP 573 DI 10.1038/351570a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FR034 UT WOS:A1991FR03400060 PM 1710783 ER PT J AU FAUCI, AS AF FAUCI, AS TI OPTIMAL IMMUNITY TO HIV - NATURAL INFECTION, VACCINATION, OR BOTH SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID NEUTRALIZATION; GP120; AIDS RP FAUCI, AS (reprint author), NIAID,BETHESDA,MD 20892, USA. NR 11 TC 7 Z9 7 U1 0 U2 1 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 JUN 13 PY 1991 VL 324 IS 24 BP 1733 EP 1735 DI 10.1056/NEJM199106133242409 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA FQ155 UT WOS:A1991FQ15500009 PM 2034251 ER PT J AU KINET, JP AF KINET, JP TI THE IMMUNOGLOBULIN-E RECEPTOR - THERAPEUTIC PERSPECTIVES SO SEMAINE DES HOPITAUX LA French DT Article; Proceedings Paper CT NATIONAL MEETING OF THE FRENCH SOC FOR ALLERGOLOGY CY JUN 21-22, 1991 CL CLERMONT FERRAND, FRANCE SP FRENCH SOC ALLERGOL DE IGE RECEPTOR; FCERI; GENE MAPPING OF THE SUBUNITS-ALPHA,BETA,GAMMA AB The high affinity receptor for immunoglobulin E is a key molecule in triggering the allergic reaction. It is a tetrameric complex of an alpha-chain, a beta-chain and two identical gamma-chains. The alpha, beta and gamma-subunits have now been cloned in three different species, including in humans. In this short review, the latest developments on the structure and function of this receptor are summarized. An increased knowledge and a better understanding of how this receptor functions may help in designing new therapeutic approaches. These potential strategies are presented. RP KINET, JP (reprint author), NIAID,MAIS,MOLEC ALLERGY & IMMUNOL SECT,TWINBROOK II BLDG,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXPANSION SCI FRANCAISE PI PARIS PA 31 BLVD LATOUR MAUBOURG, 75007 PARIS, FRANCE SN 0037-1777 J9 SEM HOP PARIS JI Sem. Hop. PD JUN 13 PY 1991 VL 67 IS 26-27 BP 1201 EP 1203 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA FT273 UT WOS:A1991FT27300006 ER PT J AU HIBBS, J PERPER, J WINEK, CL AF HIBBS, J PERPER, J WINEK, CL TI FENTANYL-LACED HEROIN - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 ALLEGHENY CTY PENN CORONERS OFF,PITTSBURGH,PA. ALLEGHENY CTY PENN DEPT LABS,PITTSBURGH,PA. RP HIBBS, J (reprint author), NIH,CLIN HEMATOL BRANCH,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 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 JUN 12 PY 1991 VL 265 IS 22 BP 2962 EP 2962 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA FP635 UT WOS:A1991FP63500032 ER PT J AU BUSTIN, M BECERRA, PS CRIPPA, MP LEHN, DA PASH, JM SHILOACH, J AF BUSTIN, M BECERRA, PS CRIPPA, MP LEHN, DA PASH, JM SHILOACH, J TI RECOMBINANT HUMAN CHROMOSOMAL-PROTEINS HMG-14 AND HMG-17 SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MOBILITY GROUP PROTEIN-14; NUCLEOSOME CORE PARTICLES; HUMAN CDNA SEQUENCE; ESCHERICHIA-COLI; ACTIVE CHROMATIN; MULTIGENE FAMILY; BINDING; TRANSCRIPTION; ANTIBODIES; GENES AB Vectors for expressing human chromosomal proteins HMG-14 and HMG-17 in bacterial cultures under the control of the temperature-inducible lambda-P(L) promoter have been constructed. The open reading frames of the cDNAs have been amplified by the polymerase chain reaction (PCR), utilizing amplimers containing desired restriction sites, thereby facilitating precise location of the initiation codon downstream from a ribosomal binding site. Expression of the recombinant proteins does not significantly affect bacterial growth. The rate of synthesis of the recombinant proteins is maximal during the initial stages of induction and slows down appreciably with time. After an initial burst of protein synthesis, the level of the recombinant protein in the bacterial extracts remains constant at different times following induction. Methods for rapid extraction and purification of the recombinant proteins are described. The recombinant proteins are compared to the proteins isolated from eucaryotic cells by electrophoretic mobility, Western analysis and nucleosome core mobility-shift assays. The ability of the proteins to shift the mobility of the nucleosome cores, but not that of DNA, can be used as a functional assay for these HMG proteins. A source for large quantities of human chromosomal proteins HMG-14 and HMG-17 will facilitate studies on their structure, cellular function and mechanism of interaction with nucleosomes. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NIDDKD,BIOTECHNOL UNIT,BETHESDA,MD 20892. RP BUSTIN, M (reprint author), NCI,MOLEC CARCINOGENESIS LAB,BLDG 37,ROOM 3D-12,BETHESDA,MD 20892, USA. RI crippa, massimo/J-6514-2016; Bustin, Michael/G-6155-2015 OI crippa, massimo/0000-0003-3214-9670; NR 36 TC 31 Z9 31 U1 1 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN 11 PY 1991 VL 19 IS 11 BP 3115 EP 3121 DI 10.1093/nar/19.11.3115 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FT160 UT WOS:A1991FT16000042 PM 2057367 ER PT J AU JING, X MILLER, RH AF JING, X MILLER, RH TI NOVEL REPEATS IN THE GENOME OF THE WOODCHUCK MARMOTA-MONAX SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PERIPHERAL-BLOOD LYMPHOCYTES; HEPATITIS-VIRUS; HEPATOCELLULAR-CARCINOMA; INFECTED WOODCHUCKS; VIRAL-DNA; TISSUES; LIVER RP JING, X (reprint author), NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892, USA. FU NIGMS NIH HHS [N01-GM-7-2110] NR 9 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN 11 PY 1991 VL 19 IS 11 BP 3151 EP 3151 DI 10.1093/nar/19.11.3151 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FT160 UT WOS:A1991FT16000049 PM 1840660 ER PT J AU HOEHE, MR EHRENREICH, H CAENAZZO, L BERRETTINI, WH AF HOEHE, MR EHRENREICH, H CAENAZZO, L BERRETTINI, WH TI TAQI IDENTIFIES A 4 ALLELE DNA POLYMORPHISM OF THE HUMAN ENDOTHELIN-1 GENE (EDN1) SO NUCLEIC ACIDS RESEARCH LA English DT Article C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RP HOEHE, MR (reprint author), NIAID,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892, USA. NR 3 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN 11 PY 1991 VL 19 IS 11 BP 3161 EP 3161 DI 10.1093/nar/19.11.3161 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FT160 UT WOS:A1991FT16000061 PM 2057379 ER PT J AU MAVALANKAR, DV CLEMENS, J AF MAVALANKAR, DV CLEMENS, J TI VITAMIN-A AND CHILDHOOD MORTALITY SO LANCET LA English DT Letter ID TRIAL RP MAVALANKAR, DV (reprint author), NICHHD,DIV PREVENT RES,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 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 JUN 8 PY 1991 VL 337 IS 8754 BP 1409 EP 1410 DI 10.1016/0140-6736(91)93088-Q PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA FP870 UT WOS:A1991FP87000023 PM 1674777 ER PT J AU CLORE, GM GRONENBORN, AM AF CLORE, GM GRONENBORN, AM TI STRUCTURES OF LARGER PROTEINS IN SOLUTION - 3-DIMENSIONAL AND 4-DIMENSIONAL HETERONUCLEAR NMR-SPECTROSCOPY SO SCIENCE LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; INTERPROTON DISTANCE RESTRAINTS; TWO-DIMENSIONAL NMR; MOLECULAR-DYNAMICS; STEREOSPECIFIC ASSIGNMENTS; SOLUTION CONFORMATION; COUPLING-CONSTANTS; AQUEOUS-SOLUTION; ANTENNAPEDIA HOMEODOMAIN; N-15-LABELED PROTEINS AB Three- and four-dimensional heteronuclear nuclear magnetic resonance (NMR) spectroscopy offers dramatic improvements in spectral resolution by spreading through-bond and through-space correlations in three and four orthogonal frequency axes. Simultaneously, large heteronuclear couplings are exploited to circumvent problems due to the larger linewidths that are associated with increasing molecular weight. These novel experiments have been designed to extend the application of NMR as a method for determining three-dimensional structures of proteins in solution beyond the limits of conventional two-dimensional NMR (approximately 100 residues) to molecules in the 150- to 300-residue range. This potential has recently been confirmed with the determination of the high-resolution NMR structure of a protein greater than 150 residues, namely, interleukin-1-beta. RP CLORE, GM (reprint author), NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892, USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 106 TC 381 Z9 384 U1 3 U2 18 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 7 PY 1991 VL 252 IS 5011 BP 1390 EP 1399 DI 10.1126/science.2047852 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FP868 UT WOS:A1991FP86800025 PM 2047852 ER PT J AU POGUN, S SCHEFFEL, U KUHAR, MJ AF POGUN, S SCHEFFEL, U KUHAR, MJ TI COCAINE DISPLACES [H-3] WIN 35,428 BINDING TO DOPAMINE UPTAKE SITES INVIVO MORE RAPIDLY THAN MAZINDOL OR GBR-12909 SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Note DE COCAINE; COCAINE RECEPTORS; MAZINDOL; GBR 12909; DOPAMINE TRANSPORTER ID MONKEYS AB Previous studies have shown that [H-3]WIN 35,428 binds preferentially to striatal cocaine receptors at the dopamine transporter after in vivo injection. In vivo binding competition studies were carried out to assess the relative rates of entry and occupancy of cocaine receptors by (-)-cocaine, mazindol and GBR 12909. After i.v. injection, (-)-cocaine occupied receptors relatively more rapidly than GBR 12,909 while mazindol was the slowest. C1 NIDA,ADDICT RES CTR,NEUROSCI BRANCH,POB 5180,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,DEPT RADIOL,DIV NUCL MED,BALTIMORE,MD 21205. RI Pogun, Sakire/A-5816-2010 FU NINDS NIH HHS [NS 15080] NR 10 TC 48 Z9 48 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JUN 6 PY 1991 VL 198 IS 2-3 BP 203 EP 205 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FU527 UT WOS:A1991FU52700014 PM 1864307 ER PT J AU LACROIX, AZ LANG, J SCHERR, P WALLACE, RB CORNONIHUNTLEY, J BERKMAN, L CURB, JD EVANS, D HENNEKENS, CH AF LACROIX, AZ LANG, J SCHERR, P WALLACE, RB CORNONIHUNTLEY, J BERKMAN, L CURB, JD EVANS, D HENNEKENS, CH TI SMOKING AND MORTALITY AMONG OLDER MEN AND WOMEN IN 3 COMMUNITIES SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; RISK-FACTORS; CIGARETTE-SMOKING; ARTERY DISEASE; FOLLOW-UP; AGE; OSTEOPOROSIS; PREDICTORS; EVENTS; HEALTH AB Background. Although cigarette smoking is the leading avoidable cause of premature death in middle age, some have claimed that no association is present among older persons. Methods. We prospectively examined the relation of cigarette-smoking habits with mortality from all causes, cardiovascular causes, and cancer among 7178 persons 65 years of age or older without a history of myocardial infarction, stroke, or cancer who lived in one of three communities: East Boston, Massachusetts; Iowa and Washington counties, Iowa; and New Haven, Connecticut. At the time of the initial interview, prevalence rates of smoking in the three communities ranged from 5.2 to 17.8 percent among women and from 14.2 to 25.8 percent among men. During five years of follow-up there were 1442 deaths, 729 due to cardiovascular disease and 316 due to cancer. Results. In both sexes, rates of total mortality among current smokers were twice what they were among participants who had never smoked. Relative risks, as adjusted for age and community, were 2.1 among the men (95 percent confidence interval, 1.7 to 2.7) and 1.8 among the women (95 percent confidence interval, 1.4 to 2.4). Current smokers had higher rates of cardiovascular mortality than those who had never smoked (as adjusted for age and community, the relative risk was 2.0 [95 percent confidence interval, 1.4 to 2.9] among the men and 1.6 [95 percent confidence interval, 1.1 to 2.3] among the women), as well as increased rates of cancer mortality (relative risk, 2.4 [95 percent confidence interval, 1.4 to 4.1] among the men and 2.4 [95 percent confidence interval, 1.4 to 3.9] among the women). In both sexes, former smokers had rates of cardiovascular mortality similar to those of the participants who had never smoked, regardless of age at cessation, whereas the rates for all cancers, as well as smoking-related cancers, remained elevated among men who had once smoked. Conclusions. Our prospective findings indicate that the mortality hazards of smoking extend well into later life, and suggest that cessation will continue to improve life expectancy in older people. C1 NIA,DEMOG & BIOMETRY,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,CHANNING LAB,DEPT MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. UNIV IOWA,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA 52242. YALE UNIV,SCH MED,DEPT EPIDEMIOL,NEW HAVEN,CT 06510. HARVARD UNIV,SCH MED,DEPT PREVENT MED,BOSTON,MA 02115. FU NIA NIH HHS [N01-AG-0-2105, N01-AG-0-2106, N01-AG-0-2107] NR 42 TC 260 Z9 265 U1 0 U2 3 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 JUN 6 PY 1991 VL 324 IS 23 BP 1619 EP 1625 DI 10.1056/NEJM199106063242303 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA FP307 UT WOS:A1991FP30700003 PM 2030718 ER PT J AU MASUR, H MEIER, P MCCUTCHAN, JA FEINBERG, J AF MASUR, H MEIER, P MCCUTCHAN, JA FEINBERG, J TI CORTICOSTEROIDS AS ADJUNCTIVE THERAPY FOR PNEUMOCYSTIS PNEUMONIA IN PATIENTS WITH AIDS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 UNIV CHICAGO,CHICAGO,IL 60637. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. RP MASUR, H (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 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 JUN 6 PY 1991 VL 324 IS 23 BP 1669 EP 1669 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA FP307 UT WOS:A1991FP30700020 ER PT J AU ARGOFF, CE COMLY, ME BLANCHETTEMACKIE, J KRUTH, HS PYE, HT GOLDIN, E KANESKI, C VANIER, MT BRADY, RO PENTCHEV, PG AF ARGOFF, CE COMLY, ME BLANCHETTEMACKIE, J KRUTH, HS PYE, HT GOLDIN, E KANESKI, C VANIER, MT BRADY, RO PENTCHEV, PG TI TYPE-C NIEMANN-PICK DISEASE - CELLULAR UNCOUPLING OF CHOLESTEROL HOMEOSTASIS IS LINKED TO THE SEVERITY OF DISRUPTION IN THE INTRACELLULAR-TRANSPORT OF EXOGENOUSLY DERIVED CHOLESTEROL SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE NIEMANN-PICK DISEASE TYPE-C; INTRACELLULAR CHOLESTEROL TRANSPORT; SKIN FIBROBLAST CULTURE; LIPID STORAGE DISORDER; (HUMAN) ID LOW-DENSITY LIPOPROTEIN; CULTURED HUMAN FIBROBLASTS; STORAGE DISORDER; RECEPTOR; CELLS; ESTERIFICATION; ACCUMULATION; REDUCTASE; METABOLISM; LYSOSOMES AB A uniquely attenuated disruption of cholesterol homeostasis has been characterized in certain Niemann-Pick, type C (NP-C) fibroblasts. Uptake of LDL-cholesterol by cultured fibroblasts derived from two clinically affected brothers with this variant biochemical phenotype led to less intracellular accumulation of unesterified cholesterol than found in other typical cell lines. This limited cholesterol lipidosis in the variant NP-C cells reflected cholesterol processing errors that differed from the cellular lesions in classical NP-C cells in the following ways: (1) a more limited intracellular distribution of the excessive unesterified cholesterol; (2) shorter and more transient delays in the induction of cholesterol-mediated homeostatic responses; and (3) more efficient intracellular transport of exogenously derived cholesterol to the plasma membrane and the endoplasmic reticulum. Activation of acyl-CoA cholesterol acyltransferase (ACAT) was greater than 100-fold in both control and NP-C fibroblasts when cell cultures were preconditioned with 25-hydroxycholesterol, but the subsequent esterification of exogenous non-lipoprotein [H-3]cholesterol remained deficient in all NP-C cells. In the variant NP-C cells conditioned with the oxysterol, this esterification of exogenous [H-3]cholesterol was less affected than in classical NP-C cultures. The NP-C mutation affects a broad spectrum of metabolic responses related to the processing of exogenously derived cholesterol. Among this pleiotropic array of deficient responses, retarded intracellular cholesterol transport appears most closely linked to the primary mutation. This conclusion is supported by two current observations: (1) the degree to which sterol transport is affected in mutant cells in turn reflects the extent to which cholesterol-homeostatic responses are compromised; and (2) sterol transport remains deficient despite concurrent normal activation of other cellular responses, such as cholesterol esterification. C1 NINCDS,DEV & METAB NEUROL BRANCH,BDG 10,ROOM 3D-12,BETHESDA,MD 20892. FAC MED LYON SUD,DEPT BIOCHEM,OULLINS,FRANCE. FAC MED LYON SUD,INSERM,U189,OULLINS,FRANCE. NIADDKD,CELLULAR & DEV BIOL LAB,ENDOCRINOL SECT,BETHESDA,MD 20892. NHLBI,EXPTL ATHEROSCLEROSIS,BETHESDA,MD 20892. OI Kaneski, Christine/0000-0003-1453-2502 NR 37 TC 27 Z9 29 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD JUN 5 PY 1991 VL 1096 IS 4 BP 319 EP 327 DI 10.1016/0925-4439(91)90068-K PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FT988 UT WOS:A1991FT98800008 PM 2065103 ER PT J AU BLUMENTHAL, SJ AF BLUMENTHAL, SJ TI ADOLESCENTS WHO ATTEMPT SUICIDE - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID RISK-FACTORS; CHILDREN RP BLUMENTHAL, SJ (reprint author), NIMH,ROCKVILLE,MD 20857, USA. NR 10 TC 2 Z9 2 U1 1 U2 1 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 JUN 5 PY 1991 VL 265 IS 21 BP 2806 EP 2807 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA FN855 UT WOS:A1991FN85500011 ER PT J AU KLEBANOFF, MA SHIONO, PH RHOADS, GG AF KLEBANOFF, MA SHIONO, PH RHOADS, GG TI SPONTANEOUS AND INDUCED-ABORTION AMONG RESIDENT PHYSICIANS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ANESTHETIC-GASES; PREGNANCY; COMPLICATIONS; EXPOSURE; OUTCOMES AB Female resident physicians are believed to be at an increased risk for a variety of third-trimester pregnancy complications. However, early pregnancy complications have been less well studied. This report compares spontaneous and induced abortions in a nationally representative sample of 5096 female medical school graduates (who experienced 1284 pregnancies) and of the sexual partners of 5000 of their male classmates (who experienced 1481 pregnancies). The response to the survey was 86.1%. The life-table probability of spontaneous abortion was 14.8% for female residents compared with 12.6% for the sexual partners of male residents. However, female residents were more likely than the male residents' sexual partners to terminate a pregnancy voluntarily (8.2% vs 2.7%). The increased risk of voluntary termination persisted when only married women were studied (3.6% vs 1.4%). However, female residents' pregnancies were at approximately half the risk of voluntary termination compared with pregnancies among the general US population of women aged 25 to 34 years. These results provide reassurance to those residents who would like to become pregnant but are concerned about the possible effect of their occupation on the course of the pregnancy. C1 DAVID & LUCILE PACKARD FDN,CTR FUTURE CHILDREN,LOS ALTOS,CA. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT ENVIRONM & COMMUNITY MED,PISCATAWAY,NJ 08854. RP KLEBANOFF, MA (reprint author), NICHHD,DIV PREVENT RES,BLDG EPN,ROOM 640,BETHESDA,MD 20892, USA. FU NICHD NIH HHS [N01-HD-9-2923] NR 19 TC 27 Z9 27 U1 1 U2 1 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 JUN 5 PY 1991 VL 265 IS 21 BP 2821 EP 2825 DI 10.1001/jama.265.21.2821 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA FN855 UT WOS:A1991FN85500030 PM 2033738 ER PT J AU MANGANEL, M TURNER, RJ AF MANGANEL, M TURNER, RJ TI RAPID SECRETAGOGUE-INDUCED ACTIVATION OF NA+/H+ EXCHANGE IN RAT PAROTID ACINAR-CELLS - POSSIBLE INTERRELATIONSHIP BETWEEN VOLUME REGULATION AND STIMULUS-SECRETION COUPLING SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MANDIBULAR SALIVARY-GLAND; AGONIST-INDUCED ACTIVATION; CYTOSOLIC FREE CALCIUM; PROTEIN-KINASE-C; ION-TRANSPORT; INTRACELLULAR PH; SUBSTANCE-P; MECHANISMS; CHANNELS; ACETYLCHOLINE AB We demonstrate a rapid activation of the Na+/H+ exchanger in intact rat parotid acini in response to muscarinic (carbachol; K1/2 = 0.4-mu-M) and alpha-adrenergic (epinephrine; K1/2 = 0.1-mu-M) stimulation. This rapid activation is apparently distinct from the relatively "slow" activation of the exchanger (t1/2 greater-than-or-equal-to 5 min) reported previously (Manganel, M., and Turner, R. J. (1989) J. Membr. Biol. 111, 191-198). This rapid activation is not produced by treatmednt of acini with active diacylglycerol analogues nor prevented by protein kinase inhibitors, arguing against the involvement of protein kinase C-dependent processes. Stimulation of the exchanger is, however, produced by concentrations of ionomycin which yield intracellular calcium levels in the physiologic (secretagogue-induced) range. In addition, chelation of intracellular calcium with 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid blocks the effect of carbachol, but calmodulin antagonists are without effect. The possibility that the rapid activation of the Na+/H+ exchanger may be associated with cell shrinkage arising from carbachol-induced calcium mobilization is explored. In support of this suggestion we present evidence that: (i) the Na+/H+ exchanger is stimulated by shrinkage of these cells, (ii) the carbachol dose dependence of Na+/H+ exchange activation correlates well with that of shrinkage (but not with that of intracellular calcium levels), and (iii) maneuvers which blunt carbachol- or calcium-induced shrinkage also blunt activation of the exchanger. We suggest that this osmoregulatory response may play an important role in maintaining ionic homeostasis during the acinar fluid secretory process. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. NR 34 TC 42 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 JUN 5 PY 1991 VL 266 IS 16 BP 10182 EP 10188 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FP086 UT WOS:A1991FP08600031 PM 1709927 ER PT J AU HOWARD, P DAY, KH KIM, KE RICHARDSON, J THOMAS, J ABRAHAM, I FLEISCHMANN, RD GOTTESMAN, MM MAURER, RA AF HOWARD, P DAY, KH KIM, KE RICHARDSON, J THOMAS, J ABRAHAM, I FLEISCHMANN, RD GOTTESMAN, MM MAURER, RA TI DECREASED CATALYTIC SUBUNIT MESSENGER-RNA LEVELS AND ALTERED CATALYTIC SUBUNIT MESSENGER-RNA STRUCTURE IN A CAMP-RESISTANT CHINESE-HAMSTER OVARY CELL-LINE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; MOUSE LYMPHOMA-CELLS; CYCLIC-AMP; REGULATORY SUBUNIT; INHIBITOR PROTEIN; MAMMALIAN-CELLS; PROLACTIN GENE; C-ALPHA; HYBRIDIZATION; PURIFICATION AB The mechanisms responsible for decreased levels of cAMP-dependent protein kinase activity in a mutant Chinese hamster ovary cell line have been examined. The cAMP-resistant Chinese hamster ovary 10260 cell line was found to possess only 20% of the cAMP-dependent protein kinase activity found in wild-type cells. The presence of decreased concentrations of the catalytic subunit in these cells was confirmed through binding studies using a radiolabeled, heat-stable inhibitor of the kinase. Cloned Chinese hamster ovary catalytic subunit cDNAs were isolated, characterized, and used as hybridization probes to examine the relative concentrations of catalytic subunit mRNAs in the wild-type and 10260 cell lines. A 40-50% decrease in the concentration of the mRNA for the C-alpha-isozyme of the catalytic subunit was observed in 10260 cells, as compared with wild-type. This decrease in catalytic subunit mRNA concentration probably accounts for a portion of the decreased kinase activity in the mutant cells. Further analysis of C-alpha mRNA by polymerase chain reaction confirmed the decreased expression of C-alpha mRNA in 10260 cells and further demonstrated the presence of two different species of C-alpha mRNA in the 10260 cells. One species of C-alpha cDNAs was indistinguishable from the wild-type cDNA, but the other species was shorter. Nucleotide sequence analysis of the amplified cDNAs led to the identification of a 191-base pair deletion in the shorter cDNA. Gene transfer studies using wild-type and 10260 C-alpha cDNAs demonstrated that the longer cDNA from the 10260 cells produced wild-type activity, but the shorter cDNA was inactive. These studies suggest that at least two alterations in gene expression are responsible for decreased cAMP-dependent protein kinase activity in the 10260 cell line. One alteration results in an approximately 2-fold decrease in the concentrations of C-alpha mRNA in the cells. The other change produces two species of C-alpha mRNA; one of the C-alpha mRNAs does not encode an active kinase. C1 UNIV IOWA,DEPT PHYSIOL & BIOPHYS,IOWA CITY,IA 52242. UPJOHN CO,DEPT CELL BIOL,KALAMAZOO,MI 49001. NCI,DIV CANC BIOL & DIAG,MOLEC BIOL LAB,BETHESDA,MD 20892. FU NHLBI NIH HHS [HL 14388]; NIDDK NIH HHS [DK25295] NR 44 TC 34 Z9 37 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 JUN 5 PY 1991 VL 266 IS 16 BP 10189 EP 10195 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FP086 UT WOS:A1991FP08600032 PM 1645343 ER PT J AU TRAPNELL, BC ZEITLIN, PL CHU, CS YOSHIMURA, K NAKAMURA, H GUGGINO, WB BARGON, J BANKS, TC DALEMANS, W PAVIRANI, A LECOCQ, JP CRYSTAL, RG AF TRAPNELL, BC ZEITLIN, PL CHU, CS YOSHIMURA, K NAKAMURA, H GUGGINO, WB BARGON, J BANKS, TC DALEMANS, W PAVIRANI, A LECOCQ, JP CRYSTAL, RG TI DOWN-REGULATION OF CYSTIC-FIBROSIS GENE MESSENGER-RNA TRANSCRIPT LEVELS AND INDUCTION OF THE CYSTIC-FIBROSIS CHLORIDE SECRETORY PHENOTYPE IN EPITHELIAL-CELLS BY PHORBOL ESTER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN KINASE-C; TRANSMEMBRANE CONDUCTANCE REGULATOR; BETA-ADRENERGIC RESPONSE; APICAL-MEMBRANE; TRACHEAL EPITHELIUM; AIRWAY EPITHELIUM; CHANNELS; TRANSPORT; EXPRESSION; LINE AB To evaluate the hypothesis that phorbol myristate acetate (PMA) might modulate the expression of the cystic fibrosis (CF) gene in epithelial cells, we examined the effect of PMA on CF mRNA levels and regulation of Cl- secretion. Strikingly, PMA down-regulated CF mRNA transcript numbers in a dose- and time-dependent manner. Importantly, in parallel with the reduction of CF mRNA levels, PMA-treated cells were unable to up-regulate Cl- secretion in a normal fashion in response to forskolin, an effect which was also dose- and time-dependent. Thus, PMA is capable of modulating expression of the CF gene and induces T84 cells to adopt the "CF phenotype" in regard to regulation of Cl- ion transport. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21205. TRANSGENE SA,F-67082 STRASBOURG,FRANCE. RP TRAPNELL, BC (reprint author), NHLBI,PULM BRANCH,BLDG 10,RM 6D03,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [K08HL02188, R01HL40178] NR 49 TC 100 Z9 100 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 JUN 5 PY 1991 VL 266 IS 16 BP 10319 EP 10323 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FP086 UT WOS:A1991FP08600052 PM 2037584 ER PT J AU LEE, RM RAPP, UR BLACKSHEAR, PJ AF LEE, RM RAPP, UR BLACKSHEAR, PJ TI EVIDENCE FOR ONE OR MORE RAF-1 KINASE KINASE(S) ACTIVATED BY INSULIN AND POLYPEPTIDE GROWTH-FACTORS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MICROTUBULE-ASSOCIATED PROTEIN-2; SERINE THREONINE KINASE; DIMENSIONAL GEL-ELECTROPHORESIS; PDGF BETA-RECEPTOR; SIGNAL TRANSDUCTION; TYROSINE PHOSPHORYLATION; 3T3-L1 ADIPOCYTES; RAPID STIMULATION; CELLS; ONCOGENE AB The protein product of the Raf-1 proto-oncogene is a protein serine/threonine kinase that is activated after stimulation of cells with insulin and other mitogens. To investigate the mechanism of this activation, we used purified Raf-1 expressed in E. coli as a substrate for a putative Raf-1 protein kinase kinase. In three different insulin-sensitive cell types, insulin activated Raf-1 kinase kinase activity in crude cytosolic cellular fractions. The insulin stimulation of this activity was evident as early as 2 min after exposure to insulin, maximal at 5-8 min, and inapparent at 15 min. Phosphoamino acid analysis of phosphorylated Raf-1 revealed that serine was the primary phosphate acceptor for the insulin-activated kinase or kinases; small amounts of phosphothreonine were also detected. The insulin effect occurred in cells depleted of protein kinase C, and in extracts depleted of endogenous Raf-1 kinase by immunodepletion; these data argue against protein kinase C or Raf-1 kinase itself being the insulin-stimulated activity. The insulin-activated kinase or kinases phosphorylated the Raf-1 protein on multiple sites in vitro, as evidenced by tryptic mapping; at least some of these appeared to overlap with sites phosphorylated in response to serum in intact cells. Several other mitogens and growth factors stimulated Raf-1 kinase kinase activity, including epidermal growth factor, platelet-derived growth factor, fibroblast growth factor, serum, and phorbol 12-myristate 13-acetate. This insulin- and mitogen-stimulated Raf-1 kinase kinase activity may play a role in mediating the phosphorylation and possibly the activation of the Raf-1 kinase by insulin and other growth factors. C1 DUKE UNIV, MED CTR, HOWARD HUGHES MED INST LABS, BOX 3897, DURHAM, NC 27710 USA. DUKE UNIV, MED CTR, DEPT MED, DIABET & METAB SECT, DURHAM, NC 27710 USA. DUKE UNIV, MED CTR, DEPT BIOCHEM, DIV ENDOCRINOL METAB & GENET, DURHAM, NC 27710 USA. NCI, VIRAL CARCINOGENESIS LAB, FREDERICK, MD 21701 USA. NR 38 TC 22 Z9 22 U1 0 U2 0 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 JUN 5 PY 1991 VL 266 IS 16 BP 10351 EP 10357 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FP086 UT WOS:A1991FP08600057 PM 2037587 ER PT J AU STOJILKOVIC, SS IIDA, T MERELLI, F TORSELLO, A KRSMANOVIC, LZ CATT, KJ AF STOJILKOVIC, SS IIDA, T MERELLI, F TORSELLO, A KRSMANOVIC, LZ CATT, KJ TI INTERACTIONS BETWEEN CALCIUM AND PROTEIN-KINASE-C IN THE CONTROL OF SIGNALING AND SECRETION IN PITUITARY GONADOTROPHS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HORMONE-SECRETION; PHORBOL ESTERS; INOSITOL TRISPHOSPHATE; CYTOSOLIC CALCIUM; CHROMAFFIN CELLS; CA-2+ CHANNELS; RELEASE; ACTIVATION; RESPONSES; OSCILLATIONS AB Single pituitary gonadotrophs exhibit episodes of spontaneous fluctuations in cytoplasmic calcium concentration ([Ca2+]i) due to entry through voltage-sensitive calcium channels (VSCC) and show prominent agonist-induced oscillations in [Ca2+]i that are generated by periodic release of intracellular Ca2+. Gonadotropin releasing hormone (GnRH) elicited three types of Ca2+ responses: at low doses, subthreshold, with an increase in basal [Ca2+]i; at intermediate doses, oscillatory, with dose-dependent modulation of spiking frequency; and at high doses, biphasic, without oscillations. Elevation of [Ca2+]i or activation of protein kinase C (PKC) did not influence the frequency of agonist-induced [Ca2+]i spikes but caused dose-dependent reductions in amplitude for all types of Ca2+ response. Stimulation of transient Ca2+ spikes by GnRH was followed by inhibition of the spontaneous fluctuations. GnRH also reduced the ability of high extracellular K+ to promote Ca2+ influx through VSCC. Activation of PKC by phorbol esters stimulated Ca2+ influx in quiescent cells but inhibited influx when VSCC were already activated, either spontaneously or by high K+. In contrast to their biphasic actions on [Ca2+]i, phorbol esters exerted only stimulatory actions on gonadotropin release, even when Ca2+ influx was concomitantly reduced. However, pituitary cells had to be primed with an appropriate [Ca2+]i level before exocytosis could be amplified by PKC. In PKC-depleted cells, all actions of phorbol esters on Ca2+ entry and amplitude modulation, and on LH release, were abolished. GnRH-induced LH secretion was also significantly reduced, especially the plateau phase of the response. These data indicate that Ca2+ and PKC serve as interacting signals during the cascade of cellular events triggered by agonist stimulation, in which Ca2+ turns cell responses on or off, and PKC amplifies the positive and negative effects of Ca2+. RP STOJILKOVIC, SS (reprint author), NICHHD,ENDOCRINOL & REPROD RES BRANCH,BLDG 10,RM B1-L400,BETHESDA,MD 20892, USA. NR 58 TC 83 Z9 83 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 JUN 5 PY 1991 VL 266 IS 16 BP 10377 EP 10384 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FP086 UT WOS:A1991FP08600060 PM 1645348 ER PT J AU MENOZZI, D VINAYEK, R JENSEN, RT GARDNER, JD AF MENOZZI, D VINAYEK, R JENSEN, RT GARDNER, JD TI DOWN-REGULATION AND RECYCLING OF HIGH-AFFINITY CHOLECYSTOKININ RECEPTORS ON PANCREATIC ACINAR-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ISOLATED RAT HEPATOCYTES; INSULIN-RECEPTORS; ENZYME-SECRETION; AMYLASE RELEASE; MONENSIN; BINDING; INTERNALIZATION; LIGAND; PINOCYTOSIS; FIBROBLASTS AB First incubating dispersed acini from rat pancreas with monensin, a cation ionophore that can inhibit recycling of receptors, inhibited binding of I-125-cholecystokin 8 (I-125-CCK-8) measured during a second incubation by as much as 50%. A maximal effect of monensin required 90 min of first incubation. Detectable inhibition of binding of I-125-CCK-8 occurred with 300 nM monensin, and inhibition increased progressively with concentrations of monensin up to 25-mu-M. Pancreatic acini possess two classes of receptors that bind I-125-CCK-8. One class has a high affinity (K(d) = 461 pM) and a low capacity for CCK (512 fmol/mg DNA); the other class has a low affinity (K(d) = 47 nM) and a high capacity for CCK (18 pmol/mg DNA). First incubating acini with monensin caused an 84% decrease in the number of high affinity CCK receptors with no change in the number of low affinity CCK receptors or the values of K(d) for either class of receptors indicating that there is recycling of high affinity CCK receptors but not low affinity CCK receptors. First incubating acini with monensin did not alter CCK-stimulated amylase secretion indicating that in contrast to previous conclusions, occupation of low affinity CCK receptors mediates CCK-stimulated enzyme secretion. Moreover, the biphasic dose-response curve for CCK-stimulated enzyme secretion from monensin-treated acini suggests that pancreatic acini also possess a third, previously unrecognized class of very low affinity CCK receptors. C1 NIDDKD,DIGEST DIS BRANCH,BLDG 10,ROOM 9C-103,BETHESDA,MD 20892. NR 40 TC 36 Z9 37 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 JUN 5 PY 1991 VL 266 IS 16 BP 10385 EP 10391 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FP086 UT WOS:A1991FP08600061 PM 2037588 ER PT J AU ROBEY, RB KWON, HM HANDLER, JS GARCIAPEREZ, A BURG, MB AF ROBEY, RB KWON, HM HANDLER, JS GARCIAPEREZ, A BURG, MB TI INDUCTION OF GLYCINEBETAINE UPTAKE INTO XENOPUS OOCYTES BY INJECTION OF POLY(A)+ RNA FROM RENAL-CELLS EXPOSED TO HIGH EXTRACELLULAR NACL SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVE RIBONUCLEIC-ACID; MAJOR ORGANIC OSMOLYTES; MESSENGER-RNA; ALDOSE REDUCTASE; MEDULLARY CELLS; LAEVIS OOCYTES; MOLECULAR-CLONING; OSMOTIC-STRESS; EXPRESSION; RAT AB Madin-Darby canine kidney (MDCK) cells accumulate glycinebetaine via Na+-dependent transport in response to hypertonic stress. When extracellular tonicity is increased by the addition of NaCl, V(max) for glycinebetaine transport increases without an associated change in K(m), consistent with an increase in the number of functioning transporters. To test whether increased transport activity results from increased gene expression, we injected poly(A)+ RNA (mRNA) from MDCK cells into Xenopus oocytes and assayed for glycinebetaine uptake in ovo. RNA-induced Na+-dependent uptake is observed in oocytes injected with mRNA from cells exposed to high extracellular NaCl, but not in oocytes injected with either water or mRNA from cells maintained in isotonic medium. Unfractionated mRNA induces glycinebetaine uptake in ovo at a rate which is approximately 3-fold higher than in water-injected controls. Size-fractionated mRNA (median size 2.8 kilobases) induces uptake at a rate which is approximately 7-fold higher than controls. Such RNA-induced transport activity in ovo is consistent with heterologous expression of Na+/glycinebetaine cotransporters encoded by renal mRNA. Increased transporter mRNA in cells exposed to hypertonicity probably underlies the pattern of expression observed in ovo. This can account for the observed rise in MDCK cell glycinebetaine transport during hypertonic stress. C1 NHLBI,KIDNEY & ELECTROLYTE LAB,BLDG 10,RM 6N307,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV NEPHROL,BALTIMORE,MD 21205. RI Robey, R. Brooks/J-7099-2013 OI Robey, R. Brooks/0000-0001-5059-3965 NR 46 TC 24 Z9 24 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 JUN 5 PY 1991 VL 266 IS 16 BP 10400 EP 10405 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FP086 UT WOS:A1991FP08600063 PM 2037590 ER PT J AU LOHSE, P MANN, WA STEIN, EA BREWER, HB AF LOHSE, P MANN, WA STEIN, EA BREWER, HB TI APOLIPOPROTEIN E-4PHILADELPHIA (GLU13-]LYS,ARG145-]CYS) HOMOZYGOSITY FOR 2 RARE POINT MUTATIONS IN THE APOLIPOPROTEIN-E GENE COMBINED WITH SEVERE TYPE-III HYPERLIPOPROTEINEMIA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR-BINDING ACTIVITY; AMINO-ACID-SEQUENCE; E MESSENGER-RNA; DENSITY LIPOPROTEIN RECEPTORS; LIPID-PROTEIN INTERACTIONS; HUMAN-E APOPROTEIN; FAMILIAL DYSBETALIPOPROTEINEMIA; PLASMA LIPOPROTEINS; SECONDARY-STRUCTURE; ANTIGENIC DETERMINANTS AB The molecular defect in a 24-year-old white female with severe type III hyperlipoproteinemia has been elucidated. The patient's apolipoprotein (apo) E migrated in the apoE-4 position on isoelectric focusing gels. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis the apoE-4 variant had a smaller apparent molecular weight than apoE-4 (Cys112 --> Arg). Sequence analysis of DNA amplified with the polymerase chain reaction revealed two nucleotide substitutions in the proband's apoE gene. A C to T mutation converted arginine (CGT) at position 145 of the mature protein to cysteine (TGT) thus creating the apoE-2* variant. A second G to A substitution at amino acid 13 led to the exchange of lysine (AAG) for glutamic acid (GAG), thereby adding 2 positive charge units to the protein and producing the apoE-5 variant. Computer analysis of the apoE-4Philadelphia gene revealed that the G to A mutation in exon 3 resulted in the loss of an AvaI restriction enzyme site. The second mutation, a C to T substitution in the fourth exon of the apoE gene, eliminated a cleavage site for the enzyme BbvI. Using these restriction fragment length polymorphisms as well as DNA sequence analysis we have demonstrated that the patient is homozygous for both point mutations in the apoE gene. C1 CHRIST HOSP,CARDIOVASC RES CTR,CINCINNATI,OH 45219. RP LOHSE, P (reprint author), NHLBI,MOLEC DIS BRANCH,BLDG 10,RM 7N117,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 75 TC 46 Z9 47 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 JUN 5 PY 1991 VL 266 IS 16 BP 10479 EP 10484 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FP086 UT WOS:A1991FP08600073 PM 1674745 ER PT J AU ALTSCHUL, SF AF ALTSCHUL, SF TI AMINO-ACID SUBSTITUTION MATRICES FROM AN INFORMATION THEORETIC PERSPECTIVE SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE HOMOLOGY; SEQUENCE COMPARISON; STATISTICAL SIGNIFICANCE; ALIGNMENT ALGORITHMS; PATTERN RECOGNITION ID DISTANTLY RELATED PROTEINS; PATTERN-RECOGNITION; NUCLEOTIDE-SEQUENCE; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; MOLECULAR-CLONING; MEMBRANE-PROTEIN; BINDING-PROTEIN; SCORING MATRIX; GENERAL-METHOD RP ALTSCHUL, SF (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20892, USA. NR 60 TC 379 Z9 389 U1 2 U2 12 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 JUN 5 PY 1991 VL 219 IS 3 BP 555 EP 565 DI 10.1016/0022-2836(91)90193-A PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FR404 UT WOS:A1991FR40400016 PM 2051488 ER PT J AU MONKS, A SCUDIERO, D SKEHAN, P SHOEMAKER, R PAULL, K VISTICA, D HOSE, C LANGLEY, J CRONISE, P VAIGROWOLFF, A GRAYGOODRICH, M CAMPBELL, H MAYO, J BOYD, M AF MONKS, A SCUDIERO, D SKEHAN, P SHOEMAKER, R PAULL, K VISTICA, D HOSE, C LANGLEY, J CRONISE, P VAIGROWOLFF, A GRAYGOODRICH, M CAMPBELL, H MAYO, J BOYD, M TI FEASIBILITY OF A HIGH-FLUX ANTICANCER DRUG SCREEN USING A DIVERSE PANEL OF CULTURED HUMAN TUMOR-CELL LINES SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID TETRAZOLIUM ASSAY; GROWTH AB We describe here the development and implementation of a pilot-scale, in vitro, anticancer drug screen utilizing a panel of 60 human tumor cell lines organized into subpanels representing leukemia, melanoma, and cancers of the lung, colon, kidney, ovary, and central nervous system. The ultimate goal of this disease-oriented screen is to facilitate the discovery of new compounds with potential cell line-specific and/or subpanel-specific antitumor activity. In the current screening protocol, each cell line is inoculated onto microtiter plates, then preincubated for 24-28 hours. Subsequently, test agents are added in five 10-fold dilutions and the culture is incubated for an additional 48 hours. For each test agent, a dose-response profile is generated. End-point determinations of the cell viability or cell growth are performed by in situ fixation of cells, followed by staining with a protein-binding dye, sulforhodamine B (SRB). The SRB binds to the basic amino acids of cellular macromolecules; the solubilized stain is measured spectrophotometrically to determine relative cell growth or viability in treated and untreated cells. Following the pilot screening studies, a screening rate of 400 compounds per week has been consistently achieved. RP MONKS, A (reprint author), NCI,FREDERICK CANC RES FACIL,PROGRAM RESOURCES INC,BLDG 432,RM 232,FREDERICK,MD 21701, USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NCI NIH HHS [N01CO-23910] NR 15 TC 2158 Z9 2187 U1 6 U2 47 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 JUN 5 PY 1991 VL 83 IS 11 BP 757 EP 766 DI 10.1093/jnci/83.11.757 PG 10 WC Oncology SC Oncology GA FN234 UT WOS:A1991FN23400012 PM 2041050 ER PT J AU FRIDMAN, R KIBBEY, MC ROYCE, LS ZAIN, M SWEENEY, TM JICHA, DL YANNELLI, JR MARTIN, GR KLEINMAN, HK AF FRIDMAN, R KIBBEY, MC ROYCE, LS ZAIN, M SWEENEY, TM JICHA, DL YANNELLI, JR MARTIN, GR KLEINMAN, HK TI ENHANCED TUMOR-GROWTH OF BOTH PRIMARY AND ESTABLISHED HUMAN AND MURINE TUMOR-CELLS IN ATHYMIC MICE AFTER COINJECTION WITH MATRIGEL SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BASEMENT-MEMBRANE; LAMININ; COLLAGENASE; METASTASIS; MODEL AB Previously we found that the reconstituted basement membrane matrix Matrigel, when premixed with human small-cell lung carcinoma cells and injected subcutaneously into athymic mice, permitted tumor growth, whereas cells injected in the absence of Matrigel did not form tumors. In the present study, we examined additional cell types and determined some of the underlying mechanisms involved in the promotion of tumor formation by Matrigel. The tumor cell lines that we studied included transformed mouse Englebreth-Holm-Swarm tumor cells (T-EHS), human submandibular carcinoma A253 cells, mouse melanoma B16F10 cells, human epidermoid carcinoma KB cells, and human primary renal cell carcinoma cells. When coinjected subcutaneously with Matrigel, these cell lines formed rapidly proliferating tumors. Primary biopsy specimens of human colon carcinoma, when dispersed and coinjected with Matrigel, also formed tumors. Only A253, KB, and B16F10 cells formed small tumors in the absence of Matrigel, but a fivefold to tenfold increase in tumor size was observed in the presence of Matrigel. These data demonstrate a useful method for improving the growth of human tumors in athymic mice. C1 NIDR,DEV BIOL LAB,BLDG 30,RM 407,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,PHARMACOL & PHARMACOGNOSY BRANCH,BETHESDA,MD 20892. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 19 TC 167 Z9 169 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 JUN 5 PY 1991 VL 83 IS 11 BP 769 EP 774 DI 10.1093/jnci/83.11.769 PG 6 WC Oncology SC Oncology GA FN234 UT WOS:A1991FN23400014 PM 1789823 ER PT J AU ALBINI, A MELCHIORI, A SANTI, L LIOTTA, LA BROWN, PD STETLERSTEVENSON, WG AF ALBINI, A MELCHIORI, A SANTI, L LIOTTA, LA BROWN, PD STETLERSTEVENSON, WG TI TUMOR-CELL INVASION INHIBITED BY TIMP-2 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID IV COLLAGENASE; TISSUE INHIBITOR; METALLOPROTEINASES; METASTASIS; ACTIVATION; MEMBRANE; INVITRO AB The 72-kd type IV collagenase is a member of the collagenase enzyme family that has been closely linked with the invasive phenotype of cancer cells. Previous studies have shown that both normal cells and highly invasive tumor cells produce the 72-kd type IV procollagenase enzyme in a complexed form consisting of the proenzyme and a novel tissue inhibitor of metalloproteinases, TIMP-2. The balance between activated enzyme and available inhibitor is thought to be a critical determinant of the matrix proteolysis associated with a variety of pathologic processes, including tumor cell invasion. In the present study, we demonstrate that alteration of the metalloproteinase-metalloproteinase-inhibitor balance in favor of excess inhibitor blocks human fibrosarcoma HT-1080 tumor cell invasion of a reconstituted basement membrane. The HT-1080 cell line produces both the 72-kd and the 92-kd type IV collagenases. Alteration of the type IV collagenases. Alteration of the type IV collagenase-inhibitor balance was achieved by addition of free TIMP-2 or antibodies to 72-kd type IV collagenase. Native, purified TIMP-2 was inhibitory in the range of 1-25-mu-g/mL. Addition of specific antiserum against the 72-kd type IV collagenase, which did not cross-react with the 92-kd type IV collagenase, inhibited HT-1080 cell invasion to the same extent. These results suggest that metalloproteinases, in particular the 72-kd type IV collagenase, are critical for tumor cell invasion of the reconstituted basement membrane. Our findings demonstrate that addition of the endogenous inhibitor TIMP-2 is able to block invasion. Thus, we recommend initiation of in vivo studies of the therapeutic potential of TIMP-2 to block tumor cell invasion and intravasation into the circulation. C1 NCI,PATHOL LAB,BLDG 10,ROOM 2A33,BETHESDA,MD 20892. IST NAZL RIC CANC,GENOA,ITALY. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 25 TC 315 Z9 323 U1 0 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 5 PY 1991 VL 83 IS 11 BP 775 EP 779 DI 10.1093/jnci/83.11.775 PG 5 WC Oncology SC Oncology GA FN234 UT WOS:A1991FN23400015 PM 1645772 ER PT J AU BRAY, GL KRONER, BS ARKIN, S ALEDON, L HILGARTNEL, MW EYSTER, ME RAGNI, M GOEDERT, JJ AF BRAY, GL KRONER, BS ARKIN, S ALEDON, L HILGARTNEL, MW EYSTER, ME RAGNI, M GOEDERT, JJ TI NATURAL-HISTORY OF INHIBITOR LOSS IN HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) INFECTED PATIENTS WITH HEMOPHILIA-A SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 CHILDRENS HOSP,NATL MED CTR,RES TRIANGLE INST,WASHINGTON,DC 20010. MT SINAI MED CTR,CORNELL MED CTR,NEW YORK,NY 10029. UNIV PITTSBURGH,MED CTR,PITTSBURGH,PA 15260. PENN STATE UNIV,MILTON S HERSHEY MED CTR,HERSHEY,PA 17033. NCI,VIRAL EPIDEMIOL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN 5 PY 1991 VL 65 IS 6 BP 677 EP 677 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA FZ966 UT WOS:A1991FZ96600098 ER PT J AU BOWDITCH, RD HALLORAN, CE PLOW, EF YAMADA, KM GINSBERG, MH AF BOWDITCH, RD HALLORAN, CE PLOW, EF YAMADA, KM GINSBERG, MH TI IDENTIFICATION OF AN ADDITIONAL REGION OF FIBRONECTIN INVOLVED IN THE BINDING TO THE PLATELET INTEGRIN ALPHA-IIB-BETA-3 SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 SCRIPPS RES INST, COMM VASC BIOL, LA JOLLA, CA 92037 USA. NCI, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN 5 PY 1991 VL 65 IS 6 BP 748 EP 748 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA FZ966 UT WOS:A1991FZ96600288 ER PT J AU TANDON, NN KRALISZ, U KLEINMANN, HK JAMIESON, GA AF TANDON, NN KRALISZ, U KLEINMANN, HK JAMIESON, GA TI ADHESION OF PLATELETS TO LAMININ-DERIVED PEPTIDES AND INHIBITION BY ANTIPEPTIDE ANTIBODIES SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 AMER RED CROSS,CELL BIOL LAB,BETHESDA,MD 20814. NIDA,LEXINGTON,KY 40583. NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN 5 PY 1991 VL 65 IS 6 BP 811 EP 811 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA FZ966 UT WOS:A1991FZ96600455 ER PT J AU GRALNICK, HR WILLIAMS, SB MCKEOWN, LP KRAMER, W GARFINKEL, L PINET, A AF GRALNICK, HR WILLIAMS, SB MCKEOWN, LP KRAMER, W GARFINKEL, L PINET, A TI A VONWILLEBRAND-FACTOR FRAGMENT COMPOSED OF AMINO-ACIDS 504LEU-728LYS DISULFIDE BONDED AT 509CYS AND 695CYS INHIBITS VONWILLEBRAND BINDING TO PLATELETS AND PLATELET-ADHESION SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 NIH,HEMATOL SERV,BETHESDA,MD 20892. BIOTECHNOL GEN REHOVOT,REHOVOT,ISRAEL. NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN 5 PY 1991 VL 65 IS 6 BP 840 EP 840 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA FZ966 UT WOS:A1991FZ96600536 ER PT J AU FUKUSHIMA, Y OKUYAMA, K KOMURO, K UEDA, M FUKUTAKE, K FUJIMAKI, M AF FUKUSHIMA, Y OKUYAMA, K KOMURO, K UEDA, M FUKUTAKE, K FUJIMAKI, M TI ELEVATED CLQ-BEARING IMMUNE-COMPLEX IN HEMOPHILIACS CONCERNING WITH VARIOUS VIRAL-INFECTION SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 NIH,DEPT BLOOD PROD,BETHESDA,MD 20892. TOKYO MED COLL,DEPT CLIN PATHOL,TOKYO 160,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN 5 PY 1991 VL 65 IS 6 BP 998 EP 998 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA FZ966 UT WOS:A1991FZ96601083 ER PT J AU GRALNICK, HR SHAFER, B WILLIAMS, SB MCKEOWN, LP VAIL, M ROBERTS, DD AF GRALNICK, HR SHAFER, B WILLIAMS, SB MCKEOWN, LP VAIL, M ROBERTS, DD TI 8G8 A MONOCLONAL-ANTIBODY RECOGNIZES THROMBOSPONDIN ON THE PLATELET SURFACE AND INHIBITS PLATELET-ADHESION TO COLLAGEN SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 NCI,CTR CLIN,HEMATOL SERV,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN 5 PY 1991 VL 65 IS 6 BP 1112 EP 1112 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA FZ966 UT WOS:A1991FZ96601498 ER PT J AU CLAGUE, MJ KNUTSON, JR BLUMENTHAL, R HERRMANN, A AF CLAGUE, MJ KNUTSON, JR BLUMENTHAL, R HERRMANN, A TI INTERACTION OF INFLUENZA HEMAGGLUTININ AMINO-TERMINAL PEPTIDE WITH PHOSPHOLIPID-VESICLES - A FLUORESCENCE STUDY SO BIOCHEMISTRY LA English DT Article ID MEMBRANE-FUSION ACTIVITY; TIME-RESOLVED FLUORESCENCE; PH-DEPENDENT FUSION; VIRUS HEMAGGLUTININ; HYDROPHOBIC BINDING; CONFORMATIONAL CHANGE; TRANSBILAYER HELICES; BILAYER INTERFACE; PROTEINS; SEQUENCE AB We have studied tryptophan fluorescence from a 20-residue synthetic peptide corresponding to the amino terminal of the HA2 subunit of the influenza virus hemagglutinin protein, a putative "fusion" peptide. Decay-associated spectra have been obtained at pH 7.4 and at pH 5 (the optimal pH for influenza virus fusion) in the presence and absence of liposomes. We demonstrate that a blue shift in the total steady-state fluorescence spectrum upon binding to liposomes is due to a movement in characteristic emission wavelength and increased lifetime of one of the resolved spectral components. In contrast, a further shift after lowering the pH is the product of a redistribution in the relative amplitudes of spectral components. Also, each decay component is quenched by spin-labels or anthroxyl groups normally located within the hydrocarbon interior of the membranes. Calculations are presented leading to an estimate of the distance of the tryptophan residue from the bilayer center, suggesting that the tryptophan residues are at or near the hydrocarbon-polar interface. No gross positional change was detected between pH values. Rotational depolarization is shown to be retarded by liposome binding, more so at low pH. C1 NCI,MEMBRANE STRUCT & FUNCT SECT,BETHESDA,MD 20892. NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. HUMBOLDT UNIV,BEREICH BIOPHYS,SEKT BIOL,O-1040 BERLIN,GERMANY. OI Clague, Michael/0000-0003-3355-9479 NR 35 TC 50 Z9 51 U1 0 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 JUN 4 PY 1991 VL 30 IS 22 BP 5491 EP 5497 DI 10.1021/bi00236a023 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FP306 UT WOS:A1991FP30600023 PM 2036418 ER PT J AU IKURA, M KAY, LE KRINKS, M BAX, A AF IKURA, M KAY, LE KRINKS, M BAX, A TI TRIPLE-RESONANCE MULTIDIMENSIONAL NMR-STUDY OF CALMODULIN COMPLEXED WITH THE BINDING DOMAIN OF SKELETAL-MUSCLE MYOSIN LIGHT-CHAIN KINASE - INDICATION OF A CONFORMATIONAL CHANGE IN THE CENTRAL HELIX SO BIOCHEMISTRY LA English DT Article ID N-15 CHEMICAL-SHIFTS; 3D NMR; HETERONUCLEAR NMR; LARGER PROTEINS; SPECTROSCOPY; ASSIGNMENT; C-13; SPECTRA; RESOLUTION; PEPTIDE AB Heteronuclear 3D and 4D NMR experiments have been used to obtain H-1, C-13, and N-15 backbone chemical shift assignments in Ca2+-loaded calmodulin complexed with a 26-residue synthetic peptide (M13) corresponding to the calmodulin-binding domain (residues 577-602) of rabbit skeletal muscle myosin light-chain kinase. Comparison of the chemical shift values with those observed in peptide-free calmodulin [Ikura, M., Kay, L. E., & Bax, A. (1990) Biochemistry 29, 4659-4667] shows that binding of M13 peptide induces substantial chemical shift changes that are not localized in one particular region of the protein. The largest changes are found in the first helix of the Ca2+-binding site I (E11-E14), the N-terminal portion of the central helix (M72-D78), and the second helix of the Ca2+-binding site IV (F141-M145). Analysis of backbone NOE connectivities indicates a change from alpha-helical to an extended conformation for residues 75-77 upon complexation with M13. This conformational change is supported by upfield changes in the C-alpha and carbonyl chemical shifts of these residues relative to M13-free calmodulin and by hydrogen-exchange experiments that indicate that the amide protons of residues 75-82 are in fast exchange (k(exch) > 10 s-1 at pH 7, 35-degrees-C) with the solvent. No changes in secondary structure are observed for the first helix of site I or the C-terminal helix of site IV. Upon complexation with M13, a significant decrease in the amide exchange rate is observed for residues T110, L112, G113, and E114 at the end of the second helix of site III. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 43 TC 138 Z9 139 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 JUN 4 PY 1991 VL 30 IS 22 BP 5498 EP 5504 DI 10.1021/bi00236a024 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FP306 UT WOS:A1991FP30600024 PM 2036419 ER PT J AU RABINOVITZ, M AF RABINOVITZ, M TI EVIDENCE FOR A ROLE OF PHOSPHOFRUCTOKINASE AND TRANSFER-RNA IN THE POLYRIBOSOME DISAGGREGATION OF AMINO-ACID DEFICIENCY SO FEBS LETTERS LA English DT Article DE PHOSPHOFRUCTOKINASE; TRANSFER RIBONUCLEIC ACID; AMINO ACID CONTROL ID POLYPEPTIDE-CHAIN INITIATION; CULTURED MAMMALIAN-CELLS; UNCHARGED TRANSFER-RNA; PROTEIN-SYNTHESIS; PHOSPHORYLATED SUGARS; STARVATION; BINDING AB The activity of rabbit muscle phosphofructokinase was inhibited by transfer ribonucleic acid. This inhibition was reduced by inclusion of an amino-acyl-tRNA charging system. The results are discussed in terms of the loss of ATP in amino acid deprived cells and in the critical role of fructose 1,6-diphosphate in peptide chain initiation. RP RABINOVITZ, M (reprint author), NCI,DIV CANC TREATMENT,BIOL CHEM LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892, USA. NR 27 TC 7 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUN 3 PY 1991 VL 283 IS 2 BP 270 EP 272 DI 10.1016/0014-5793(91)80605-3 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA FT387 UT WOS:A1991FT38700026 PM 1828439 ER PT J AU KUMAR, VD LEE, L EDWARDS, BFP AF KUMAR, VD LEE, L EDWARDS, BFP TI REFINED CRYSTAL-STRUCTURE OF YTTERBIUM-SUBSTITUTED CARP PARVALBUMIN 4.25 AT 1.5-A, AND ITS COMPARISON WITH THE NATIVE AND CADMIUM-SUBSTITUTED STRUCTURES SO FEBS LETTERS LA English DT Article DE CALCIUM BINDING PROTEIN; LANTHANIDE; YTTERBIUM-SUBSTITUTED; X-RAY STRUCTURE ID CALCIUM-BINDING PROTEINS; NUCLEAR MAGNETIC-RESONANCE; EARTH METAL IONS; LANTHANIDE IONS; ALPHA-AMYLASE; PROBES; SITES; LUMINESCENCE; RESOLUTION AB The crystal structure of carp parvalbumin 4.25 containing a 1:1 molar ratio of ytterbium chloride to protein has been refined at 1.5 angstrom resolution by restrained least-squares methods to a crystallographic R value of 0.199. The crystal structure confirms the NMR studies, which suggest that low concentrations of ytterbium cause an extensive displacement of calcium from the EF metal binding site. A comparison of the ytterbium-substituted model with the native and cadmium-substituted structure show no significant differences, except around the substituted EF metal-binding region. The displacement of calcium by ytterbium at the EF site has caused a movement in the polypeptide backbone of Ser-91 and Asp-92. This movement resulted in an increase in the number of oxygen ligands bound to ytterbium in the EF site from seven to eight. C1 WAYNE STATE UNIV,SCH MED,DEPT BIOCHEM,DETROIT,MI 48202. UNIV WINDSOR,DEPT CHEM & BIOCHEM,WINDSOR N9B 3P4,ONTARIO,CANADA. RP KUMAR, VD (reprint author), NCI,CTR CANC RES & DEV,ABL BASIC RES PROGRAM,MACROMOLEC STRUCT LAB,FREDERICK,MD 21701, USA. FU NCI NIH HHS [N01-CO-74101]; NCRR NIH HHS [RR 02945]; NIGMS NIH HHS [GM33192] NR 27 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUN 3 PY 1991 VL 283 IS 2 BP 311 EP 316 DI 10.1016/0014-5793(91)80616-B PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA FT387 UT WOS:A1991FT38700037 PM 2044772 ER PT J AU HORWITZ, RJ CHRISTIANSEN, RG ROGERS, C AF HORWITZ, RJ CHRISTIANSEN, RG ROGERS, C TI THE ACUTE CARE THEATER CONFERENCE SO ACADEMIC MEDICINE LA English DT Editorial Material ID COMPUTER C1 UNIV ILLINOIS,COLL MED,DEPT MED,ROCKFORD,IL. RP HORWITZ, RJ (reprint author), NIH,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUN PY 1991 VL 66 IS 6 BP 321 EP 322 DI 10.1097/00001888-199106000-00004 PG 2 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA FQ173 UT WOS:A1991FQ17300004 PM 2069651 ER PT J AU WU, YW CHIK, CL ALBERTSON, BD LINEHAN, WM KNAZEK, RA AF WU, YW CHIK, CL ALBERTSON, BD LINEHAN, WM KNAZEK, RA TI INHIBITORY EFFECTS OF GOSSYPOL ON ADRENAL-FUNCTION SO ACTA ENDOCRINOLOGICA LA English DT Article ID HUMAN ADRENOCORTICAL-CELLS; MEMBRANES; FLUIDITY; ENZYMES; INVITRO; AGENT; RATS AB Gossypol, an antifertility agent, has inhibitory actions on many membrane-associated enzymes, suggesting that this agent might have a generalized effect on cell membranes. This hypothesis was examined in the present study using membranes and dispersed cells prepared from human and rat adrenal glands. Four parameters were determined: microviscosity as measured by fluorescence polarization of human adrenal microsomal- and mitochondrial-enriched membranes, adrenal steroidogenic enzymes; and cAMP and cortisol responses to ACTH. It was found that gossypol increased the polarization constants of microsomes and mitochondria in a dose-dependent manner. Of the three adrenal enzymes tested, both 3-beta-hydroxysteroid dehydrogenase DELTA-5-DELTA-4 isomerase and 11-hydroxylase were inhibited by gossypol, but not 21-hydroxylase. Using intact human adrenocortical cells, high doses of gossypol also inhibited the ACTH-stimulated cAMP and cortisol levels. The in vivo corticosterone response to ACTH in rats subjected to chronic gossypol treatment was also found to be reduced. These findings suggest that gossypol has multiple effects on adrenal function. Its effects on membrane microviscosity, adrenal steroidogenesis, cAMP and corticosterone responses to ACTH stimulation probably occur through a generalized membrane effect. C1 UNIV ALBERTA,HERITAGE MED RES CTR,ROOM 362,CLIN WING,EDMONTON T6G 2S2,ALBERTA,CANADA. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD. NCI,SURG BRANCH,BETHESDA,MD 20892. NR 26 TC 8 Z9 8 U1 0 U2 1 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0001-5598 J9 ACTA ENDOCRINOL-COP JI Acta Endocrinol. PD JUN PY 1991 VL 124 IS 6 BP 672 EP 678 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FV712 UT WOS:A1991FV71200010 PM 1648853 ER PT J AU LIFSON, JD RAUSCH, DM KALYANARAMAN, VS HWANG, KM EIDEN, LE AF LIFSON, JD RAUSCH, DM KALYANARAMAN, VS HWANG, KM EIDEN, LE TI SYNTHETIC PEPTIDES ALLOW DISCRIMINATION OF STRUCTURAL FEATURES OF CD4(81-92) IMPORTANT FOR HIV-1 INFECTION VERSUS HIV-1-INDUCED SYNCYTIUM FORMATION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN CD4; ENVELOPE GLYCOPROTEIN; MONOCLONAL-ANTIBODIES; BINDING-SITE; RESIDUES; DOMAIN; GP120; IDENTIFICATION; CYTOPATHICITY AB Benzylated peptides with a primary amino acid sequence corresponding to either human CD4(81-92) (#18), or chimpanzee CD4(81-92) (#18C), were equipotent inhibitors of human immunodeficiency virus type 1 (HIV-1) infection of CD4+ cells and high-affinity binding of I-125-gp120 to CD4+ cells. The chimpanzee-based CD4(81-92) peptide, however, which differs from the human peptide by a single amino acid substitution (E for G) at position 87, was considerably less potent than the human CD4(81-92)-based peptide congener to inhibit HIV-1-induced cell-cell fusion. These data suggest that a portion of the CD4 molecule contained within the sequence CD4(81-92) is involved in binding gp120 during both HIV-1 infection and HIV-1-induced syncytium formation in human cells, but that the presence of a glutamic acid at position 87 in this sequence is more critical for the CD4/gp120 interaction leading to syncytium formation than for the CD4/gp120 interaction leading to primary infection of CD4-positive cells. The region CD4(81-92) may critically contribute to CD4-mediated HIV-1 pathogenesis in humans, and its alteration might explain the lack of pathogenic sequelae of HIV-1 infection in chimpanzees.1,2 C1 NIMH,MOLEC & CELLULAR NEUROBIOL UNIT,CELL BIOL LAB,BLDG 36,ROOM 3A-17,BETHESDA,MD 20892. GENELABS INC,REDWOOD CITY,CA 94063. ADV BIOSCI LABS,ROCKVILLE,MD 20895. OI Eiden, Lee/0000-0001-7524-944X FU NIAID NIH HHS [AI25922] NR 33 TC 21 Z9 21 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 JUN PY 1991 VL 7 IS 6 BP 521 EP 527 DI 10.1089/aid.1991.7.521 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA FU361 UT WOS:A1991FU36100005 PM 1931230 ER PT J AU PAL, R MUMBAUER, S HOKE, G LAROCCA, R MYERS, C SARNGADHARAN, MG STEIN, CA AF PAL, R MUMBAUER, S HOKE, G LAROCCA, R MYERS, C SARNGADHARAN, MG STEIN, CA TI EFFECT OF EVANS BLUE AND TRYPAN BLUE ON SYNCYTIA FORMATION AND INFECTIVITY OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-I AND TYPE-II INVITRO SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID DEXTRAN SULFATE; HTLV-III; T-CELLS; PHOSPHOROTHIOATE ANALOGS; MONONUCLEAR PHAGOCYTES; REVERSE-TRANSCRIPTASE; VIRION BINDING; SOLUBLE CD4; HIV; REPLICATION AB Polyanionic compounds were used to inhibit infectivity of human immunodeficiency virus in vitro. Suramin, Evans blue, and Trypan blue were shown to inhibit syncytia formation normally observed when HIV-1-infected cells are cocultured with CD4+ cells. The inhibition was more pronounced with Evans blue than with any of the other polyanions studied. The inhibitory effect was significantly weaker in HIV-2 systems. However, the reverse transcriptase activities of both types of viruses were inhibited by Evans blue. Another polyanionic compound, phosphorothioate 28-mer cytidine homopolymer (SdC28) was shown to inhibit syncytium formation induced by HIV-1-and HIV-2-infected cells in an identical manner. Evans blue showed partial blocking of gp120 binding to CD4 in a solid-phase enzyme-linked immunosorbent assay (ELISA). These results suggest that the polyanionic dyes may exert their antiviral effects, at least in part, by interfering with the binding and fusion of HIV with susceptible T cells. C1 NCI,MED BRANCH,BETHESDA,MD 20892. RP PAL, R (reprint author), ADV BIOSCI LABS INC,5510 NICHOLSON LANE,KENSINGTON,MD 20895, USA. FU NCI NIH HHS [N01-CP-87214] NR 32 TC 12 Z9 12 U1 0 U2 1 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 JUN PY 1991 VL 7 IS 6 BP 537 EP 543 DI 10.1089/aid.1991.7.537 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA FU361 UT WOS:A1991FU36100007 PM 1718343 ER PT J AU LANDS, WEM AF LANDS, WEM TI ACETATE METABOLISM - NEW MYSTERIES FROM OLD DATA SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Editorial Material ID UNITED-STATES ADULTS; NUTRIENT INTAKE; BODY-WEIGHT; ALCOHOL; ETHANOL; ADENOSINE RP LANDS, WEM (reprint author), NIAAA,ALCOHOL DRUG ABUSE & MENTAL HLTH ADM,DIV BASIC RES,5600 FISHERS LANE,ROOM 16C-06,ROCKVILLE,MD 20857, USA. NR 25 TC 8 Z9 8 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 JUN PY 1991 VL 15 IS 3 BP 393 EP 394 DI 10.1111/j.1530-0277.1991.tb00535.x PG 2 WC Substance Abuse SC Substance Abuse GA FT843 UT WOS:A1991FT84300001 PM 1877724 ER PT J AU ENGLER, MM KARANIAN, JW SALEM, N AF ENGLER, MM KARANIAN, JW SALEM, N TI ETHANOL INHALATION AND DIETARY N-6, N-3, AND N-9 FATTY-ACIDS IN THE RAT - EFFECT ON PLATELET AND AORTIC FATTY-ACID COMPOSITION SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE GAMMA-LINOLENIC ACID; FATTY ACIDS; ETHANOL; PLATELETS; AORTA ID ACYL-COA DESATURASES; ARACHIDONIC-ACID; ALCOHOL CONSUMPTION; BLOOD-PRESSURE; PHOSPHOLIPIDS; INGESTION; LIPIDS AB The effects of 18-carbon n-6, n-3, and n-9 fatty acid diets and ethanol exposure on the fatty acyl composition of platelets and vascular tissue were examined. An experimental design was devised to control the dietary content of 18-carbon fatty acids. The levels of 18:3n6, 18:3n3 and 18:1n9 were varied by a formulation of dietary oils which contained similar proportions of 18:2n6. Male Sprague-Dawley rats were fed a purified diet containing 11% by weight of either borage oil (BOR) rich in 18:3n6, linseed/safflower oil (LSO) rich in 18:3n3, or sesame oil (SES) rich in 18:1n9 for 7 weeks and exposed to ethanol vapors by means of inhalation for the final 6 days of the dietary regimen. Moderate blood ethanol levels of 118 +/- 6.6 mg/dl were obtained. Total lipids were extracted from platelets and aortae, and the fatty acid distributions were analyzed by gas chromatography. BOR feeding resulted in increases in the proportion of n-6 fatty acids (18:3n6, 20:3n6, 20:4n6) in platelets and aorta. Animals fed the LSO diet had increased levels of n-3 fatty acids (18:3n3, 20:5n3, 22:6n3). The SES-based diet resulted in an increase in 18:1n9 in both aorta and platelets. Following ethanol exposure alone, the most marked change in the fatty acid profile was a decrase in 20:4n6 in the platelet. This effect was not observed in rats supplemented with BOR. No significant changes were observed in the aortic fatty acid content at this level of ethanol exposure. The results suggested that, in the rat, a diet enriched with BOR effectively prevented ethanol-induced alterations in platelet fatty acid composition. C1 NIAAA,DIV INTRAMURAL CLIN & BIOL RES,CLIN STUDIES LAB,ANALYT CHEM SECT,BETHESDA,MD. NR 30 TC 15 Z9 15 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 1991 VL 15 IS 3 BP 483 EP 488 DI 10.1111/j.1530-0277.1991.tb00547.x PG 6 WC Substance Abuse SC Substance Abuse GA FT843 UT WOS:A1991FT84300013 PM 1877733 ER PT J AU KLUES, HG STATLER, LS WALLACE, RB ROBERTS, WC AF KLUES, HG STATLER, LS WALLACE, RB ROBERTS, WC TI MASSIVE CALCIFICATION OF A PORCINE BIOPROSTHESIS IN THE AORTIC-VALVE POSITION AND THE ROLE OF CALCIUM SUPPLEMENTS SO AMERICAN HEART JOURNAL LA English DT Note C1 NHLBI,PATHOL BRANCH,BLDG 10,ROOM 2N258,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT MED,DIV CARDIOL,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,DEPT SURG,WASHINGTON,DC 20007. NR 1 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 1991 VL 121 IS 6 BP 1829 EP 1831 DI 10.1016/0002-8703(91)90042-G PN 1 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA FP713 UT WOS:A1991FP71300042 PM 2035405 ER PT J AU ROBERTS, CS ROBERTS, WC AF ROBERTS, CS ROBERTS, WC TI AORTIC DISSECTION WITH THE ENTRANCE TEAR IN ABDOMINAL-AORTA SO AMERICAN HEART JOURNAL LA English DT Note C1 NHLBI,SURG BRANCH,BLDG 10,ROOM 2N258,BETHESDA,MD 20892. NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NR 3 TC 27 Z9 31 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 1991 VL 121 IS 6 BP 1834 EP 1835 DI 10.1016/0002-8703(91)90044-I PN 1 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA FP713 UT WOS:A1991FP71300044 PM 2035406 ER PT J AU LUNN, G SANSONE, EB AF LUNN, G SANSONE, EB TI VALIDATED METHODS FOR DEGRADING HAZARDOUS CHEMICALS - SOME HALOGENATED COMPOUNDS SO AMERICAN INDUSTRIAL HYGIENE ASSOCIATION JOURNAL LA English DT Article ID NICKEL-ALUMINUM-ALLOY; CARCINOGENICITY; MUTAGENICITY; STRAIN; MICE AB Two techniques were investigated for degrading a number of halogenated compounds of commercial and research importance. Reductive dehalogenation with nickel-aluminum alloy in potassium hydroxide solution was used to degrade iodomethane, chloroacetic acid, trichloroacetic acid, 2-chloroethanol, 2-brontoethanol, 2-chloroethylamine, 2-bromoethylamine, 1-bromobutane, 1-iodobutane, 2-bromobutane, 2-iodobutane, 2-bromo-2-methylpropane, 2-iodo-2-methylpropane, 3-chloropyridine, fluorobenzene, chlorobenzene, bromobenzene, iodobenzene, 4-fluoroaniline, 2-chloroaniline, 3-chloroaniline, 4-chloroaniline, 4-fluoronitrobenzene, 2-chloronitrobenzene, 3-chloronitrobenzene, 4-chloronitrobenzene, benzyl chloride, benzyl bromide, alpha,alpha-dichlorotoluene, and 3-aminobenzotrifluoride. The products were generally those obtained by replacing the halogen with hydrogen although concomitant reduction of the other groups was also observed. Bibenzyl was produced during the reduction of benzyl chloride, benzyl bromide, and alpha,alpha-dichlorotoluene. Refluxing with ethanolic potassium hydroxide was used to degrade iodomethane, chloroacetic acid, 2-fluoroethanol, 2-chloroethanol, 2-bromoethanol, 1-chlorobutane, 1-bromobutane, 1-iodobutane, 2-bromobutane, 2-iodobutane, 2-bromo-2-methylpropane, 2-iodo-2-methylpropane, benzyl chloride, benzyl bromide, 1-bromononane, 1-chlorodecane, and 1-bromodecane. The products were the corresponding ethyl ethers. 2-Methylaziridine was cleaved with nickel-aluminum alloy in potassium hyroxide solution to a mixture of isopropylamine and n-propylamine. In all cases, the compounds were completely degraded and only nonmutagenic reaction mixtures were produced. C1 NCI,FREDERICK CANC RES & DEV CTR,ENVIRONM CONTROL & RES PROGRAM,PROGRAM RESOURCES INC,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74102] NR 21 TC 8 Z9 8 U1 0 U2 1 PU AMER INDUSTRIAL HYGIENE ASSOC PI FAIRFAX PA 2700 PROSPERITY AVE #250, FAIRFAX, VA 22031-4307 SN 0002-8894 J9 AM IND HYG ASSOC J JI Am. Ind. Hyg. Assoc. J. PD JUN PY 1991 VL 52 IS 6 BP 252 EP 257 DI 10.1202/0002-8894(1991)052<0252:VMFDHC>2.0.CO;2 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA KC587 UT WOS:A1991KC58700008 PM 1858668 ER PT J AU MOREIRA, JE BALL, WD MIRELS, L HAND, AR AF MOREIRA, JE BALL, WD MIRELS, L HAND, AR TI ACCUMULATION AND LOCALIZATION OF 2 ADULT ACINAR CELL SECRETORY PROTEINS DURING DEVELOPMENT OF THE RAT SUBMANDIBULAR-GLAND SO AMERICAN JOURNAL OF ANATOMY LA English DT Article ID ACID-RICH PROTEINS; PAROTID-GLAND; MUCIN-GLYCOPROTEIN; CYTODIFFERENTIATION; EXPRESSION; RNA AB The seromucous acinar cells of the adult rat submandibular gland secrete a characteristic mucin glycoprotein and a family of unusual glutamine/glutamic acid-rich proteins (GRP). Monoclonal antibodies to the mucin and GRP localized in a very few Type III cells in glands of newborn and 1 day-old rats, using light and electron microscopic immunocytochemistry. Both mucin and GRP reactivities were present in the polymorphic Type IIIP granules during the 1st postnatal week. By 9 days after birth, the granules contained both mucin and GRP and were mucous-like in appearance. At earlier stages, however, cells containing only GRP or mucin could be found, indicating that the initiation of GRP and mucin biosynthesis may not be coordinately regulated. No reactivity was seen in the neonatal Type I cells or in duct cells at any age. Northern and Western blot analysis showed GRP mRNA and protein levels to be barely detectable at birth, with marked increases during the first 2 postnatal weeks. In contrast, Western blots of B1-immunoreactive proteins (B1-IP) showed levels highest in the 1st week and markedly decreased in the adult. Immunocytochemical colocalization, using gold particles of different sizes, showed that the B1-IP, mucin, and GRP colocalized in the granules. These results strengthen the hypothesis that the adult acinar cells develop from the neonatal Type III cells. No evidence was obtained for the involvement of Type I cells in the pathway of acinar cell development. C1 HOWARD UNIV,SCH MED,DEPT ANAT,520 W ST,WASHINGTON,DC 20059. HOWARD UNIV,COLL MED,CTR CANC,WASHINGTON,DC 20059. NIDR,CLIN INVESTIGAT & PATIENT CARE BRANCH,BETHESDA,MD 20892. COLUMBIA UNIV,SCH DENT & ORAL SURG,NEW YORK,NY 10027. FU NIDCR NIH HHS [DE-06635] NR 32 TC 50 Z9 50 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 0002-9106 J9 AM J ANAT PD JUN PY 1991 VL 191 IS 2 BP 167 EP 184 DI 10.1002/aja.1001910204 PG 18 WC Anatomy & Morphology SC Anatomy & Morphology GA FN813 UT WOS:A1991FN81300003 PM 1677796 ER PT J AU DOLLAR, AL KRAGEL, AH FERNICOLA, DJ WACLAWIW, MA ROBERTS, WC AF DOLLAR, AL KRAGEL, AH FERNICOLA, DJ WACLAWIW, MA ROBERTS, WC TI COMPOSITION OF ATHEROSCLEROTIC PLAQUES IN CORONARY-ARTERIES IN WOMEN LESS-THAN-40 YEARS OF AGE WITH FATAL CORONARY-ARTERY DISEASE AND IMPLICATIONS FOR PLAQUE REVERSIBILITY SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MYOCARDIAL-INFARCTION; YOUNG-ADULTS; MORPHOMETRIC ANALYSIS; REGRESSION DIETS; RISK-FACTORS; MONKEYS AB This study analyzes the composition of atherosclerotic plaques in the 4 major epicardial coronary arteries in 8 women < 40 years of age (mean 34) with fatal coronary artery disease (CAD) and compares these data to previous studies of 37 adults > 45 years of age (mean 59) with fatal CAD. Histologic sections were taken at 5-mm intervals from the entire lengths of the right, left main, left anterior descending and left circumflex coronary arteries. With the use of a computerized morphometry system, analysis of the 4 major epicardial coronary arteries showed the major component of plaque to be a combination of cellular (mean percent total plaque area = 65%, standard error = 6%) and dense (19%, standard error = 6%) fibrous tissue. Arterial segments narrowed > 75% in cross-sectional area from these young women were compared with similarly narrowed arteries from 37 older patients (32 men [86%]) with fatal CAD previously reported by this laboratory, and showed significantly more cellular fibrous tissue and lipid-rich foam cells, and lesser amounts of dense fibrous and heavily calcified tissue. The large amount of lipid-containing foam cells and relative lack of acellular scar tissue in coronary plaques in these young women suggests a greater potential for reversibility of these plaques in this subset of patients with CAD. C1 NHLBI,PATHOL BRANCH,BLDG 10,ROOM 2N258,BETHESDA,MD 20892. NHLBI,BIOSTAT BRANCH,BETHESDA,MD 20892. NR 20 TC 51 Z9 53 U1 1 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 1 PY 1991 VL 67 IS 15 BP 1223 EP 1227 DI 10.1016/0002-9149(91)90931-A PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA FN811 UT WOS:A1991FN81100012 PM 2035445 ER PT J AU GERTZ, SD MALEKZADEH, S DOLLAR, AL KRAGEL, AH ROBERTS, WC AF GERTZ, SD MALEKZADEH, S DOLLAR, AL KRAGEL, AH ROBERTS, WC TI COMPOSITION OF ATHEROSCLEROTIC PLAQUES IN THE 4 MAJOR EPICARDIAL CORONARY-ARTERIES IN PATIENTS GREATER-THAN-OR-EQUAL-TO-90 YEARS OF AGE SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MYOCARDIAL-INFARCTION; DISEASE; AUTOPSY; HEART AB The composition of atherosclerotic plaques in 733 five-mm segments of the 4 major (left main, left anterior descending, left circumflex and right) epicardial coronary arteries of 18 patients greater-than-or-equal-to 90 years of age was determined by computerized planimetric analysis. By analysis of all coronary segments of all patients > 90, the plaques consisted primarily of fibrous tissue (87 +/- 8%) with calcific deposits (7 +/- 6%), pultaceous debris (5 +/- 4%) and foam cells (1 +/- 1%) occupying a much smaller percentage of plaque area. Analysis of composition according to the 4 degrees of luminal cross-sectional area narrowing revealed marked step-wise increases in pultaceous debris (from 0 +/- 0% at 0 to 25% narrowing to 18 +/- 22% at 76 to 100% narrowing, p = 0.0001) and calcific deposits (from 0 +/- 0 to 10 +/- 15%, p = 0.002), and decreases in fibrous tissue (from 99 +/- 3 to 71 +/- 23%, p = 0.0001) and area occupied by the media (from 35 +/- 8 to 16 +/- 8%, p = 0.0001). When the analysis was restricted to sections narrowed > 75%, no significant differences were found in plaque components or medial area between patients with (11 patients) and without (7 patients) myocardial infarcts at necropsy. C1 HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT ANAT & EMBRYOL,IL-91010 JERUSALEM,ISRAEL. RP GERTZ, SD (reprint author), NHLBI,PATHOL BRANCH,BLDG 10,ROOM 2N258,BETHESDA,MD 20892, USA. NR 17 TC 37 Z9 39 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 1 PY 1991 VL 67 IS 15 BP 1228 EP 1233 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA FN811 UT WOS:A1991FN81100013 PM 2035446 ER PT J AU YUSUF, S HELD, P FURBERG, C AF YUSUF, S HELD, P FURBERG, C TI UPDATE OF EFFECTS OF CALCIUM-ANTAGONISTS IN MYOCARDIAL-INFARCTION OR ANGINA IN LIGHT OF THE 2ND DANISH VERAPAMIL INFARCTION TRIAL (DAVIT-II) AND OTHER RECENT STUDIES SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material ID PROGRESSION C1 OSTRA HOSPITAL,GOTHENBURG,SWEDEN. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. RP YUSUF, S (reprint author), NHLBI,CLIN TRIALS BRANCH,FED 5C10,BETHESDA,MD 20892, USA. NR 9 TC 223 Z9 230 U1 1 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 1 PY 1991 VL 67 IS 15 BP 1295 EP 1297 DI 10.1016/0002-9149(91)90944-G PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA FN811 UT WOS:A1991FN81100025 PM 2035457 ER PT J AU MCSHANE, LM CLARK, LC COMBS, GF TURNBULL, BW AF MCSHANE, LM CLARK, LC COMBS, GF TURNBULL, BW TI REPORTING THE ACCURACY OF BIOCHEMICAL MEASUREMENTS FOR EPIDEMIOLOGIC AND NUTRITION STUDIES SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE LABORATORY ACCURACY; QUALITY CONTROL, VARIANCE COMPONENTS; ASSAY MAXIMUM PERCENT ERROR; HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY; VITAMIN-E AB Procedures for reporting and monitoring the accuracy of biochemical measurements are presented. They are proposed as standard reporting procedures for laboratory assays for epidemiologic and clinical-nutrition studies. The recommended procedures require identification and estimation of all major sources of variability and explanations of laboratory quality control procedures employed. Variance-components techniques are used to model the total variability and calculate a maximum percent error that provides an easily understandable measure of laboratory precision accounting for all sources of variability. This avoids ambiguities encountered when reporting an SD that may taken into account only a few of the potential sources of variability. Other proposed uses of the total-variability model include estimating precision of laboratory methods for various replication schemes and developing effective quality control-checking schemes. These procedures are demonstrated with an example of the analysis of alpha-tocopherol in human plasma by using high-performance liquid chromatography. C1 CORNELL UNIV,DIV NUTR SCI,ITHACA,NY 14853. UNIV ARIZONA,ARIZONA CANC CTR,TUCSON,AZ 85721. CORNELL UNIV,SCH OPERAT RES & IND ENGN,ITHACA,NY 14853. NIH,BETHESDA,MD 20892. FU NCI NIH HHS [R01 CA4976]; NIGMS NIH HHS [R01 GM 28364] NR 9 TC 19 Z9 20 U1 0 U2 3 PU AMER SOC CLIN NUTRITION INC 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 JUN PY 1991 VL 53 IS 6 BP 1354 EP 1360 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA FN399 UT WOS:A1991FN39900004 PM 2035462 ER PT J AU FERRARO, R BOYCE, VL SWINBURN, B DEGREGORIO, M RAVUSSIN, E AF FERRARO, R BOYCE, VL SWINBURN, B DEGREGORIO, M RAVUSSIN, E TI ENERGY-COST OF PHYSICAL-ACTIVITY ON A METABOLIC WARD IN RELATIONSHIP TO OBESITY SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE ENERGY EXPENDITURE; WEIGHT-MAINTENANCE DIET ID EXPENDITURE AB The energy cost of physical activity on a metabolic ward was derived from the difference between the energy requirement to maintain body weight on a metabolic ward and sedentary 24-h energy expenditure measured in a respiratory chamber in 56 nondiabetic male subjects. The cost of physical activity was negatively correlated with body weight (r = -0.67, P < 0.0001) and with percent body fat (r = -0.48, P < 0.0005). In a subgroup of 15 subjects selected for strict weight stability (rate of daily weight change < +/- 35 g/d), similar negative correlations were observed between energy cost of activity and body weight (r = -0.61, P < 0.01) and percent body fat (r = -0.51, P = 0.05). The ratio of active to sedentary energy expenditure, an index of physical activity, was also negatively correlated with body weight and percent body fat (r = -0.74, P < 0.002) and r = -0.61, P < 0.02, respectively). These results suggest that heavier subjects on a metabolic ward are less active and expend less energy in physical activity than do lighter subjects. RP FERRARO, R (reprint author), NIDDKD,CLIN DIABET & NUTR SECT,PHOENIX,AZ, USA. NR 17 TC 39 Z9 39 U1 1 U2 2 PU AMER SOC CLIN NUTRITION INC 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 JUN PY 1991 VL 53 IS 6 BP 1368 EP 1371 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA FN399 UT WOS:A1991FN39900006 PM 2035463 ER PT J AU HOWARD, BV BOGARDUS, C RAVUSSIN, E FOLEY, JE LILLIOJA, S MOTT, DM BENNETT, PH KNOWLER, WC AF HOWARD, BV BOGARDUS, C RAVUSSIN, E FOLEY, JE LILLIOJA, S MOTT, DM BENNETT, PH KNOWLER, WC TI STUDIES OF THE ETIOLOGY OF OBESITY IN PIMA-INDIANS SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT CONF ON OBESITY AND CARDIOVASCULAR DISEASE IN MINORITY POPULATIONS CY AUG 28-29, 1990 CL BETHESDA, MD SP NHLBI DE OBESITY; FAT CELLS; LIPOPROTEIN LIPASE; ATPASE; LIPOPROTEINS; FATTY ACIDS; INSULIN RESISTANCE; CALORIE INTAKE; ENERGY EXPENDITURE ID BILIARY LIPID-METABOLISM; NORMAL GLUCOSE-TOLERANCE; POSTRECEPTOR ABNORMALITIES; INVITRO INSENSITIVITY; INSULIN RESISTANCE; ENERGY-EXPENDITURE; CALORIC INTAKE; INVIVO; ANTILIPOLYSIS; TRANSPORT AB Studies have been conducted on various metabolic characteristics of lean and obese Pima Indians, including studies of fat-cell morphology, glucose transport, and lipolysis; lipoprotein lipase activities; sodium-potassium ATPase in red cells, adipocytes, and fibroblasts; lipids and lipoprotein metabolism; fatty acid metabolism; and sterol balance. Insulin concentrations, insulin binding, insulin action on glucose disposal, fatty acid metabolism, and islet function were compared in lean and obese individuals, and the relationship between insulin resistance and muscle morphology was explored. To explore potential abnormalities in energy balance, calorie intake and gastric emptying were compared in lean and obese Pimas and measurements of energy expenditure were performed. The data suggest that there are multiple metabolic differences that accompany obesity in Native Americans. A lower metabolic rate was a determinant of future weight gain, and abnormalities in use of free fatty acids and cell insulin action were suggested, which emphasize the need for further studies in these areas. C1 NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,PHOENIX,AZ. SANDOZ RES INST,E HANOVER,NJ. RP HOWARD, BV (reprint author), MEDLANTIC RES FDN,108 IRVING ST,NW,WASHINGTON,DC 20010, USA. RI Lillioja, Stephen/A-8185-2012 NR 29 TC 26 Z9 26 U1 0 U2 1 PU AMER SOC CLIN NUTRITION INC 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 JUN PY 1991 VL 53 IS 6 SU S BP S1577 EP S1585 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA FP059 UT WOS:A1991FP05900014 PM 1827703 ER PT J AU KNOWLER, WC PETTITT, DJ SAAD, MF CHARLES, MA NELSON, RG HOWARD, BV BOGARDUS, C BENNETT, PH AF KNOWLER, WC PETTITT, DJ SAAD, MF CHARLES, MA NELSON, RG HOWARD, BV BOGARDUS, C BENNETT, PH TI OBESITY IN THE PIMA-INDIANS - ITS MAGNITUDE AND RELATIONSHIP WITH DIABETES SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT CONF ON OBESITY AND CARDIOVASCULAR DISEASE IN MINORITY POPULATIONS CY AUG 28-29, 1990 CL BETHESDA, MD SP NHLBI DE OBESITY; PIMA INDIANS; BODY MASS INDEX; DIABETES ID MELLITUS; WEIGHT; HEIGHT; ADIPOSITY; PREGNANCY; INDEXES; WOMEN AB Members of the Pima Indian population are obese, on average, as estimated by the body mass index (BMI). Young adults have had the highest BMIs and there have been modest increases in age- and sex-specific mean BMIs for the past 25 y. These observations suggest that the older adults have had less exposure to factors leading to obesity than have the younger adults. Compared with children studied early in this century, present-day Pima children are much heavier for height, suggesting that the degree of obesity has increased since that time. Obesity in the Pimas is familial and has complex relationships with non-insulin-dependent diabetes mellitus, a common disease in this population. Obesity predicts the development of diabetes; once people have diabetes, however, they tend to lose weight. Thus, obesity should not be studied in this population without also considering diabetes, which tends to limit the degree of obesity. C1 MEDLANT RES FDN,WASHINGTON,DC. CLEVELAND CLIN FDN,PHOENIX,AZ. NIDDKS,CLIN DIABET & NUTR SECT,PHOENIX,AZ. RP KNOWLER, WC (reprint author), NIDDKS,DIABET & ARTHRITIS EPIDEMIOL SECT,PHOENIX,AZ, USA. RI Nelson, Robert/B-1470-2012 NR 36 TC 221 Z9 225 U1 0 U2 2 PU AMER SOC CLIN NUTRITION INC 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 JUN PY 1991 VL 53 IS 6 SU S BP S1543 EP S1551 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA FP059 UT WOS:A1991FP05900008 PM 2031485 ER PT J AU KUMANYAKA, SK OBARZANEK, E STEVENS, VJ HEBERT, PR WHELTON, PK AF KUMANYAKA, SK OBARZANEK, E STEVENS, VJ HEBERT, PR WHELTON, PK TI WEIGHT-LOSS EXPERIENCE OF BLACK-AND-WHITE PARTICIPANTS IN NHLBI-SPONSORED CLINICAL-TRIALS SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT CONF ON OBESITY AND CARDIOVASCULAR DISEASE IN MINORITY POPULATIONS CY AUG 28-29, 1990 CL BETHESDA, MD SP NHLBI DE BODY WEIGHT; OBESITY; WEIGHT REDUCTION; CLINICAL TRIALS; BLACKS; WHITES; HYPERTENSION; RACIAL DIFFERENCES ID IRON-DEFICIENCY ANEMIA; UNITED-STATES ADULTS; INTERVENTION PROGRAM; BLOOD-PRESSURE; FINAL REPORT; BODY-WEIGHT; OBESITY; HYPERTENSION; WOMEN; DIET AB We examined race-specific weight-loss results from two randomized, multicenter trials: the Hypertension Prevention Trial (HPT) and the Trials of Hypertension Prevention (TOHP). Mean weight change from baseline averaged 2.2 kg less in black women than in white women during 18 mo of follow-up in TOHP and 2.7 kg less during 36 mo of follow-up in HPT. Mean weight loss averaged 2.0 kg less in black than in white men in TOHP and 1.4 kg less in HPT. Because of greater weight gain in black control subjects, a comparison of net weight loss (change in intervention minus change in control participants, within-race) showed a less marked difference than did black-white differences in weight loss within the actively treated group. Thus, relative to weight that would have been gained without the intervention, the experience of blacks and whites was more similar. Racial differences in weight loss may result from a combination of behavioral, sociocultural, biological, and programmatic factors. C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. KAISER PERMANENTE CTR HLTH RES,PORTLAND,OR. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,CHANNING LAB,BOSTON,MA 02115. JOHNS HOPKINS UNIV,DEPT EPIDEMIOL,BALTIMORE,MD 21218. RP KUMANYAKA, SK (reprint author), PENN STATE UNIV,DEPT NUTR,S-126 HENDERSON,UNIVERSITY PK,PA 16802, USA. FU NHLBI NIH HHS [R01 HL 25192, R01 HL 25194, R01 HL 25202] NR 50 TC 171 Z9 172 U1 0 U2 0 PU AMER SOC CLIN NUTRITION INC 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 JUN PY 1991 VL 53 IS 6 SU S BP S1631 EP S1638 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA FP059 UT WOS:A1991FP05900022 PM 2031498 ER PT J AU DEVANEY, K JAFFE, ES AF DEVANEY, K JAFFE, ES TI THE SURGICAL PATHOLOGY OF GASTROINTESTINAL HODGKINS-DISEASE SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article ID TUMOR-ASSOCIATED EOSINOPHILIA; REED-STERNBERG CELLS; MONOCLONAL-ANTIBODIES; MALIGNANT-LYMPHOMA; LEU-M1; TRACT; DIAGNOSIS; AUTOPSY; TISSUES AB The files of the National Cancer Institute were searched for all surgical specimens from the gastrointestinal (GI) tract with the diagnosis of Hodgkin's disease (HD) that were accessioned during the years 1953-1990; six patients with a histologically reconfirmed diagnosis were identified. Of these patients, four presented with GI HD and two had recurrent HD. Primary HD appeared in the stomach (three patients) and the duodenum (one patient); recurrent HD after diagnosis in a conventional nodal site appeared in the stomach (one patient) and the colon (one patient). One of the cases of primary gastric disease was a composite lymphoma consisting of HD and diffuse large cell lymphoma. In view of the rarity of GI tract involvement by HD, a diagnosis of primary GI HD should be viewed with skepticisms; support for such a diagnosis may be provided by both classic histopathologic features of HD and immunostaining, but no single feature can be regarded as pathognomonic. C1 NCI,PATHOL LAB,BLDG 10,ROOM 2N202,BETHESDA,MD 20892. USN HOSP,DEPT PATHOL,BETHESDA,MD 20814. NR 31 TC 32 Z9 34 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JUN PY 1991 VL 95 IS 6 BP 794 EP 801 PG 8 WC Pathology SC Pathology GA FP776 UT WOS:A1991FP77600009 PM 2042588 ER PT J AU MURPHY, EL FIGUEROA, JP GIBBS, WN HOLDINGCOBHAM, M CRANSTON, B MALLEY, K BODNER, AJ ALEXANDER, SS BLATTNER, WA AF MURPHY, EL FIGUEROA, JP GIBBS, WN HOLDINGCOBHAM, M CRANSTON, B MALLEY, K BODNER, AJ ALEXANDER, SS BLATTNER, WA TI HUMAN T-LYMPHOTROPIC VIRUS TYPE-I (HTLV-I) SEROPREVALENCE IN JAMAICA .1. DEMOGRAPHIC DETERMINANTS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE AGE FACTORS; HTLV-I; HTLV-I ANTIBODIES; PARITY; SEX FACTORS; SOCIOECONOMIC FACTORS ID CELL LEUKEMIA-LYMPHOMA; TROPICAL SPASTIC PARAPARESIS; UNITED-STATES; C RETROVIRUS; NATION-WIDE; ANTIBODIES; TRANSMISSION; INFECTION; JAPAN; PREVALENCE AB During 1985 and 1986, the authors measured antibodies to human T-lymphotropic virus type I (HTLV-I) in a cohort of 13,260 Jamaicans from all parts of the island who applied for food-handling licenses. HTLV-I seroprevalence was strongly age and sex dependent, rising from 1.7% (10-19 years) to 9.1% (greater-than-or-equal-to 70 years) in men and from 1.9% (10-19 years) to 17.4% (greater-than-or-equal-to 70 years) in women. In a logistic regression analysis, women were more likely to be seropositive than were men, and farmers, laborers, and the unemployed were more likely to be HTLV-I seropositive than were those reporting student or professional occupations. In men, African ethnicity was associated with HTLV-L seropositivity in the univariate analysis but was not a risk factor after adjustment for age and sex. There was a trend toward higher age-stratified HTLV-I seroprevalence among younger women who reported more pregnancies, but older multigravidas had lower rates of HTLV-I seropositivity. Persons born outside Jamaica had significantly lower seroprevalence than did those born in Jamaica, but they were of slightly different ethnic and occupational compositions than those born in Jamaica. C1 NCI,VIRAL EPIDEMIOL SECT,BETHESDA,MD 20892. MINIST HLTH,KINGSTON,JAMAICA. CORNWALL REG HLTH DEPT,MONTEGO BAY,JAMAICA. ATLANTIC RES CO,BETHESDA,MD. BIOTECH RES LABS INC,ROCKVILLE,MD. FU NCI NIH HHS [N01-CP-31006] NR 30 TC 139 Z9 142 U1 0 U2 2 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1991 VL 133 IS 11 BP 1114 EP 1124 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA FP762 UT WOS:A1991FP76200005 PM 2035515 ER PT J AU MALONEY, EM MURPHY, EL FIGUEROA, JP GIBBS, WN CRANSTON, B HANCHARD, B HOLDINGCOBHAM, M MALLEY, K BLATTNER, WA AF MALONEY, EM MURPHY, EL FIGUEROA, JP GIBBS, WN CRANSTON, B HANCHARD, B HOLDINGCOBHAM, M MALLEY, K BLATTNER, WA TI HUMAN T-LYMPHOTROPIC VIRUS TYPE-I (HTLV-I) SEROPREVALENCE IN JAMAICA .2. GEOGRAPHIC AND ECOLOGIC DETERMINANTS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE ALTITUDE; ECOLOGY; HTLV-I; HTLV-I ANTIBODIES; HTLV-I INFECTIONS; SOCIOECONOMIC FACTORS ID TROPICAL SPASTIC PARAPARESIS; LEUKEMIA-LYMPHOMA VIRUS; INFECTION; TRANSMISSION; ANTIBODIES; COLOMBIA AB An island-wide cohort of 13,260 Jamaicans who applied for food-handling licenses during 1985 and 1986 were tested for antibodies to human T-cell lymphotropic virus type I (HTLV-I). Demographic and residence history data were linked to geographic and ecologic measures of elevation, rainfall, crop-growing areas, population density, and additional measures of urbanization and correlated with HTLV-I antibody status. By logistic regression analysis (performed separately for men and women), men and women who currently resided at low elevation (less-than-or-equal-to 1,000 ft (305 m)) were more likely to be HTLV-I infected than were those residing at high elevation. Men, but not women, who were born in citrus-growing areas were more likely to be HTLV-I infected than were men who were born in other areas. By univariate analysis, there was a significant positive trend of increasing HTLV-I seroprevalence with increasing amount of annual rainfall associated with birthplace and primary residence areas. However, these associations did not remain significant after adjusting for age and sex. These environmental associations raise the possibility of new modes of viral transmission or host response to infection, although they may simply be surrogates for socioeconomic status, breastfeeding habits, or sexual behavior, which are known determinants of HTLV-I zero prevalence. C1 MINIST HLTH,KINGSTON,JAMAICA. UNIV W INDIES,DEPT PATHOL,KINGSTON 7,JAMAICA. CORNWALL REG HLTH DEPT,MONTEGO BAY,JAMAICA. ATLANTIC RES CO,ROCKVILLE,MD. RP MALONEY, EM (reprint author), NCI,VIRAL EPIDEMIOL SECT,EXECUT PLAZA N,ROOM 434,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CP-31006] NR 28 TC 21 Z9 22 U1 0 U2 1 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1991 VL 133 IS 11 BP 1125 EP 1134 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA FP762 UT WOS:A1991FP76200006 PM 2035516 ER PT J AU BAKER, WJ HARGIS, JB DANESI, R LAROCCA, RV AF BAKER, WJ HARGIS, JB DANESI, R LAROCCA, RV TI THE EFFECT OF RHGM-CSF ON THE PROLIFERATION OF OSTEOGENIC-SARCOMA CELLS SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE GM-CSF; OSTEOSARCOMA; CELL GROWTH ID COLONY-STIMULATING FACTOR; HEMATOPOIETIC GROWTH-FACTORS; TUMOR-CELLS; GM-CSF; CARCINOMA; LEUKEMIA; LINES AB Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) promotes the growth of a variety of hematopoietic and nonhematopoietic cells, both benign and malignant. There is now evidence that osteoblast-like cells produce GM-CSF and their growth is stimulated by this cytokine in vitro. We have studied the effect of rhGM-CSF on DNA synthesis and cell proliferation in the human osteogenic sarcoma cell lines U-20S, G-292, MG-63, and HOS. RhGM-CSF stimulated a dose-dependent increase in radioactive thymidine incorporation in each of the four cell lines in the presence of serum-free media, and in two cell lines (HOS and U-20S) in the presence of fetal bovine serum (FBS). In addition, rhGM-CSF produced significant increases in cell proliferation in two cell lines (MG-63 and U-20S) in the presence of 2% FBS. These results suggest that GM-CSF may have an important role in the biology of human osteogenic sarcoma cells. The clinical implications of these findings merit further investigation. C1 WALTER REED ARMY MED CTR,DEPT MED,DIV HEMATOL ONCOL,WASHINGTON,DC 20307. NCI,CLIN ONCOL PROGRAM,MED BRANCH,BETHESDA,MD 20892. NR 17 TC 6 Z9 6 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 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 1991 VL 37 IS 2 BP 84 EP 87 DI 10.1002/ajh.2830370205 PG 4 WC Hematology SC Hematology GA FM888 UT WOS:A1991FM88800004 PM 2069168 ER PT J AU MINOR, JR AF MINOR, JR TI 10 YEARS EXPERIENCE WITH AIDS - CURRENT STATUS AND FUTURE-PROSPECTS SO AMERICAN JOURNAL OF HOSPITAL PHARMACY LA English DT Editorial Material RP MINOR, JR (reprint author), NIH,CTR CLIN,DEPT PHARM,BLDG 10,ROOM N-257,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 0002-9289 J9 AM J HOSP PHARM JI Am. J. Hosp. Pharm. PD JUN PY 1991 VL 48 IS 6 BP 1296 EP 1297 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FN806 UT WOS:A1991FN80600032 PM 1858816 ER PT J AU AMANTEA, MA AF AMANTEA, MA TI ROLE OF CD4 IN HIV-INFECTION AND THERAPY SO AMERICAN JOURNAL OF HOSPITAL PHARMACY LA English DT Letter ID RECOMBINANT SOLUBLE CD4; HTLV-III/LAV; T4 MOLECULE; AIDS; RETROVIRUS; ANTIGEN; PROTEIN; RECEPTOR; COMPLEX; FORM RP AMANTEA, MA (reprint author), NIH,CTR CLIN,BETHESDA,MD 20892, USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 0002-9289 J9 AM J HOSP PHARM JI Am. J. Hosp. Pharm. PD JUN PY 1991 VL 48 IS 6 BP 1300 EP 1300 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FN806 UT WOS:A1991FN80600035 PM 1677530 ER PT J AU OKAYAMA, H BRANTLY, M HOLMES, M CRYSTAL, RG AF OKAYAMA, H BRANTLY, M HOLMES, M CRYSTAL, RG TI CHARACTERIZATION OF THE MOLECULAR-BASIS OF THE ALPHA-1-ANTITRYPSIN F-ALLELE SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID ALPHA-1-ANTITRYPSIN DEFICIENCY; ENZYMATIC AMPLIFICATION; EMPHYSEMA; INHIBITOR; DISEASE; GENE; DNA; POLYMERASE; PHENOTYPES; VARIANTS AB Alpha-1-antitrypsin (alpha-1-AT), the major serum inhibitor of neutrophil elastase, is a highly polymorphic serum protein associated with characteristic isoelectric-focusing (IEF) patterns for most variants. To characterize the molecular basis of the anodal F variant, the DNA sequence of the coding exons of an FZ individual was determined. The F allele differed from the normal M1(Val213) alpha-1-AT allele by a single nucleotide transversion of cytosine to thymidine, which results in the amino acid substitution Arg223 CGT --> Cys TGT. Inheritance of the F mutation was confirmed by family analysis using allele-specific amplification. In the context that the normal alpha-1-AT molecule has only one cysteine residue, a mutation resulting in the addition of a second cysteine may influence the three-dimensional form of the protein and/or permit interaction with other plasma proteins with free-SH groups and may be responsible for the observation that the major F alpha-1-AT bands often migrate as doublets in IEF gels. C1 NHLBI,PULM BRANCH,BLDG 10,ROOM 6D03,BETHESDA,MD 20892. NR 29 TC 16 Z9 17 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUN PY 1991 VL 48 IS 6 BP 1154 EP 1158 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA FP092 UT WOS:A1991FP09200018 PM 2035534 ER PT J AU AMOS, CI MARTINEZ, M BALE, SJ AF AMOS, CI MARTINEZ, M BALE, SJ TI CAN A SUSCEPTIBILITY LOCUS FOR SCHIZOPHRENIA BE EXCLUDED FROM CHROMOSOME 5Q11-13 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter ID LOD SCORE; LINKAGE; MODELS C1 NIMH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. RP AMOS, CI (reprint author), NCI,FAMILY STUDIES SECT,BETHESDA,MD 20892, USA. RI Martinez, Maria/B-3111-2013 OI Martinez, Maria/0000-0003-2180-4537 NR 14 TC 5 Z9 5 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUN PY 1991 VL 48 IS 6 BP 1206 EP 1208 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA FP092 UT WOS:A1991FP09200031 PM 2035539 ER PT J AU JABLONSKI, S AF JABLONSKI, S TI SYNDROME - LE-MOT-DE-JOUR SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE SYNDROME; HISTORY; TERMINOLOGY AB Syndrome is one of the oldest terms in the medical vocabulary. It has been used as a designation for those disorders that were marked by etiologically nonspecific similar groups of manifestations up to the time of Sydenham. His contention that the terms syndrome and disease were in fact synonymous explains in part infrequent use of syndrome in the literature until the latter part of the 19th century. Redefinition of syndrome early in the 20th century as a disorder characterized by the concurrence of symptoms which are causally related, and further refinement of the definition as a condition marked by a cluster of symptoms occurring together coincidentally, gradually restored the popularity of the term to where syndrome is now one of the most frequently used designations of morbid states in the literature. There are numerous definitions of syndrome currently in use. One which is accepted by most dysmorphologists, geneticists, and some clinicians states that syndrome is an etiologically defined entity of unknown pathogenesis. However, most writers use the term randomly to denote any abnormal condition, whether medical,social, or behavioral, when a more satisfactory designation cannot be found or created, or to emphasize special complexity (syndromic qualities?) of already named diseases, or merely to be amusing. The post-Sydenham custom of naming of syndromes after physicians gave way in the mid-20th century to methods wherein syndrome names incorporate clinical, etiological, genetic, and other significant characteristics. Other methods used in designating syndromes include using the names of the first patient known to be affected, acronyms and abbreviations, personal names of all kinds, and the like. Syndrome, once a unique and valuable term in the arsenal of medical vocabulary, has lost much of its usefulness through misuse. C1 NATL LIB MED,BETHESDA,MD 20209. NR 38 TC 8 Z9 9 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JUN 1 PY 1991 VL 39 IS 3 BP 342 EP 346 DI 10.1002/ajmg.1320390319 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA FK915 UT WOS:A1991FK91500018 PM 1867288 ER PT J AU BERNARDINI, I EVANS, MI NICOLAIDES, KH ECONOMIDES, DL GAHL, WA AF BERNARDINI, I EVANS, MI NICOLAIDES, KH ECONOMIDES, DL GAHL, WA TI THE FETAL CONCENTRATING INDEX AS A GESTATIONAL AGE-INDEPENDENT MEASURE OF PLACENTAL DYSFUNCTION IN INTRAUTERINE GROWTH-RETARDATION SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 58TH ANNUAL MEETING OF THE CENTRAL ASSOC OBSTETRICIANS AND GYNECOLOGISTS CY OCT 11-13, 1990 CL LOUISVILLE, KY SP CENT ASSOC OBSTETRICIANS & GYNECOLOGISTS DE FETAL CONCENTRATING INDEX; INTRAUTERINE GROWTH RETARDATION; AMINO ACIDS; CARNITINE ID PLASMA AMINO-ACIDS; CARNITINE; FETUSES; CORDOCENTESIS; STARVATION; DIAGNOSIS; PREGNANCY AB In previous work we have shown, using cordocentesis to obtain fetal blood, that fetuses with intrauterine growth retardation are hypoxic and suffer from in utero starvation of nutrients. In this study we have developed gestational age curves for fetal blood amino acids and carnitine that now allow the development of a new parameter, the fetal concentration index, which is the numeric mean of the fetal/maternal ratio of six essential and nonessential concentrated amino acids. Our data shown that this index does not vary with gestation in either normal pregnancies (1.83 +/- 0.42, mean +/- SD) or pregnancies with intrauterine growth retardation (1.46 +/- 0.38), but the index is markedly reduced in intrauterine growth retardation (p < 0.001). These results suggest that, because cordocentesis has become very safe in experienced hands, cordocentesis to obtain the fetal concentrating index might ethically be obtained in cases of fetuses at risk for intrauterine growth retardation, to devise strategies for intervention before the onset of severe hypoxia and morphometric changes. C1 NICHHD,HUMAN GENET BRANCH,HUMAN BIOCHEM GENET SECT,BLDG 10,ROOM 95242,900 ROCKVILLE PIKE,BETHESDA,MD 20892. WAYNE STATE UNIV,HUTZEL HOSP,DEPT OBSTET GYNECOL,DIV REPROD GENET,DETROIT,MI 48202. WAYNE STATE UNIV,HUTZEL HOSP,DEPT MOLEC BIOL,DETROIT,MI 48202. WAYNE STATE UNIV,HUTZEL HOSP,DEPT GENET,DETROIT,MI 48202. WAYNE STATE UNIV,HUTZEL HOSP,CTR MOLEC BIOL,DETROIT,MI 48202. UNIV LONDON KINGS COLL,SCH MED,HARRIS BIRTHRIGHT CTR,DEPT OBSTET & GYNECOL,LONDON WC2R 2LS,ENGLAND. NR 24 TC 22 Z9 22 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUN PY 1991 VL 164 IS 6 BP 1481 EP 1490 PN 1 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA FR470 UT WOS:A1991FR47000011 PM 2048594 ER PT J AU CATES, W WASSERHEIT, JN AF CATES, W WASSERHEIT, JN TI GENITAL CHLAMYDIAL INFECTIONS - EPIDEMIOLOGY AND REPRODUCTIVE SEQUELAE SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT SYMP AT THE 1990 ANNUAL MEETING OF THE AMERICAN COLLEGE OF OBSTETRICIANS AND GYNECOLOGISTS - OB-GYN CARE IN THE 1990S : THE CHLAMYDIA CHALLENGE CY MAY 06, 1990 CL SAN FRANCISCO, CA SP AMER COLL OBSTETRICIANS & GYNECOLOGISTS, PFIZER LAB DE PELVIC INFLAMMATORY DISEASE; ENDOMETRITIS; SALPINGITIS; ECTOPIC PREGNANCY; NONSPECIFIC URETHRITIS ID PELVIC INFLAMMATORY DISEASE; SEXUALLY-TRANSMITTED DISEASES; TUBAL FACTOR INFERTILITY; ORAL-CONTRACEPTIVE USE; FAMILY-PLANNING CLINICS; NEISSERIA-GONORRHOEAE; ACUTE SALPINGITIS; TRACHOMATIS INFECTION; ECTOPIC PREGNANCY; MYCOPLASMA-HOMINIS AB Genital chlamydial infection is increasing and is now more common than gonorrhea. A sizable percentage of chlamydial infections of the lower genital tract in women progress to endometritis and salpingitis. Tubal infertility and ectopic pregnancy are important sequelae. Failure to control chlamydial infections reflects the following four factors: (1) Many cases are mild or asymptomatic; (2) diagnostic tests are expensive and technically demanding; (3) at least 7 days of multiple-dose therapy are currently required; and (4) partner notification is not routinely performed. Thus early identification of infected persons and compliance with curative therapy are less likely than with other sexually transmitted bacterial diseases. C1 NIAID, MICROBIOL & INFECT DIS PROGRAM, STD BRANCH, BETHESDA, MD 20892 USA. RP CATES, W (reprint author), CTR DIS CONTROL, CTR PREVENT SERV, DIV STD HIV PREVENT, TECH INFORMAT SERV E06, ATLANTA, GA 30333 USA. NR 124 TC 376 Z9 384 U1 0 U2 9 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 JUN PY 1991 VL 164 IS 6 SU S BP 1771 EP 1781 PN 2 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA FR817 UT WOS:A1991FR81700002 PM 2039031 ER PT J AU MAGRATH, IT AF MAGRATH, IT TI AFRICAN BURKITTS-LYMPHOMA - HISTORY, BIOLOGY, CLINICAL-FEATURES, AND TREATMENT SO AMERICAN JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE BURKITTS LYMPHOMA; AFRICA; JAW; EPSTEIN-BARR VIRUS ID EPSTEIN-BARR VIRUS; C-MYC ONCOGENE; ACQUIRED IMMUNODEFICIENCY SYNDROME; BONE-MARROW INVOLVEMENT; CELL-LINES; LYMPHOPROLIFERATIVE DISORDERS; UNDIFFERENTIATED LYMPHOMAS; COMBINATION CHEMOTHERAPY; HOMOSEXUAL MEN; B-CELLS AB Dennis Burkitt's first description of the African tumor that is now known by his name appeared in 1958. In the brief intervening span of 32 years, this lymphoma has provided an extraordinarily valuable paradigm that has afforded insights into topics that encompass the entire discipline of oncology. These include the origins of lymphoid neoplasms at epidemiological, cellular, and molecular levels, and the efficacy of chemotherapy in rapidly progressive, widely disseminated lymphomas. In addition, epidemiological considerations led to the discovery of a new virus, the Epstein-Barr virus, which has proved to be an important human pathogen. This virus probably plays a pathogenetic role in several neoplastic diseases, including the lymphoproliferative syndromes associated with inherited and acquired immunodeficiency. Small, noncleaved cell lymphoma is the latest histological designation of the category of lymphomas that includes Burkitt's lymphoma. This tumor, which is biologically heterogeneous, has become notorious because of its high incidence in individuals infected with the human immunodeficiency virus, which is providing a second, potentially fertile model for the exploration of the pathogenesis of lymphoid neoplasms. Already, enough is known of the pathogenesis of Burkitt's lymphoma to permit the first tentative steps toward the development of novel therapeutic approaches directed toward the molecular genetic abnormalities associated with the neoplasm. In this article, the history, biology, clinical features, and treatment of African Burkitt's lymphoma are reviewed. RP MAGRATH, IT (reprint author), NCI,PEDIAT BRANCH,LYMPHOMA BIOL SECT,BLDG 10,ROOM 13N240,BETHESDA,MD 20892, USA. NR 131 TC 91 Z9 92 U1 2 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-8562 J9 AM J PEDIAT HEMATOL PD SUM PY 1991 VL 13 IS 2 BP 222 EP 246 PG 25 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA FL396 UT WOS:A1991FL39600019 PM 2069232 ER PT J AU CULP, DJ GRAHAM, LA LATCHNEY, LR HAND, AR AF CULP, DJ GRAHAM, LA LATCHNEY, LR HAND, AR TI RAT SUBLINGUAL GLAND AS A MODEL TO STUDY GLANDULAR MUCOUS CELL SECRETION SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE SUBLINGUAL SALIVARY GLAND; MUCIN GLYCOPROTEINS; MUSCARINIC CHOLINERGIC RECEPTORS ID SALIVARY-GLANDS; SUBSTANCE-P; CHROMATOGRAPHY; MUCIN; OLIGOSACCHARIDES; GLYCOPROTEINS; SENSITIVITY; PEPTIDE; PROTEIN; CHAINS AB To study the regulation of mucous cell secretion, we have developed an in vitro cell model consisting of enzymatically dispersed mucous acinar structures (cell aggregates) from rat sublingual glands. Histological and ultrastructural evidence demonstrates that the cell aggregates are highly enriched in mucous cells, retain the morphological and ultrastructural features observed in intact glands, and undergo transition to an extensive secretory state when stimulated by 10-mu-M carbachol. The secretory responsiveness of the cell aggregates was verified in pharmacological studies. Carbachol stimulated secretion in a dose-dependent manner with high affinity (concentration causing half-maximal response = 0.3-mu-M) and was completely inhibited by atropine. Secretion was also stimulated by vasoactive intestinal peptide and substance P but not by alpha- or beta-adrenergic agonists. Biochemical characterization of secretion during nonstimulated and carbachol-stimulated conditions (after preincubation in [H-3]glucosamine) demonstrated that, in response to carbachol, cell aggregates synthesized and secreted mucins which were similar to mucin glycoproteins isolated from whole glands. Collectively, our results establish that the rat sublingual cell aggregate model is a viable and pharmacologically responsive cell system to study the regulation of mucous cell secretion. C1 NIDR, CLIN INVEST & PATIENT CARE BRANCH, BETHESDA, MD 20892 USA. RP CULP, DJ (reprint author), UNIV ROCHESTER, DEPT DENT RES, 601 ELMWOOD AVE, ROCHESTER, NY 14642 USA. NR 32 TC 20 Z9 21 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUN PY 1991 VL 260 IS 6 BP C1233 EP C1244 PN 1 PG 12 WC Physiology SC Physiology GA FU841 UT WOS:A1991FU84100013 ER PT J AU KIM, DK HEINEMAN, FW BALABAN, RS AF KIM, DK HEINEMAN, FW BALABAN, RS TI EFFECTS OF BETA-HYDROXYBUTYRATE ON OXIDATIVE-METABOLISM AND PHOSPHORYLATION POTENTIAL IN CANINE HEART INVIVO SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE OXIDATIVE PHOSPHORYLATION; OXYGEN CONSUMPTION; P-31 NUCLEAR MAGNETIC RESONANCE; CORONARY BLOOD FLOW; CREATINE PHOSPHATE; ADENOSINE TRIPHOSPHATE; ADENOSINE DIPHOSPHATE; EPINEPHRINE; LACTATE; GLUCOSE; PYRUVATE; ALANINE ID PERFUSED RAT-HEART; KETONE-BODIES; PYRUVATE-DEHYDROGENASE; OXYGEN-CONSUMPTION; LIPID-METABOLISM; FATTY-ACIDS; INTACT DOG; P-31-NMR; MYOCARDIUM; SPECTROSCOPY AB Beta-Hydroxybutyrate (HBA) is an effective substrate for mitochondrial respiration (MVo2) in the heart. Myocardial HBA oxidation is associated with high mitochondrial NADH and an inhibition of glycolytic flux. The purpose of this study was to investigate if the infusion of HBA in vivo could modify the coupling mechanisms between myocardial MVo2 and work in the presence and absence of epinephrine. The extraction of several oxidized metabolites, O2, and HBA was measured during the infusion of HBA as well as the high-energy phosphate metabolites using P-31-nuclear magnetic resonance spectroscopy. HBA infusion did not affect the MVo2 or function of the heart with or without epinephrine infusion. However, HBA increased the phosphorylation potential by decreasing inorganic phosphate and the calculated free ADP concentration under both conditions. This is consistent with HBA increasing the mitochondrial NADH, which results in an increase in the phosphorylation potential without modifying function. These data demonstrate that substrates, specifically HBA, can modulate the cardiac phosphorylation potential in vivo. The most likely mechanism for this effect is through the mitochondrial NADH concentration. C1 NIH,CARDIAC ENERGET LAB,BLDG 1,RM B3-07,BETHESDA,MD 20892. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 34 TC 39 Z9 39 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUN PY 1991 VL 260 IS 6 BP H1767 EP H1773 PN 2 PG 7 WC Physiology SC Physiology GA FU845 UT WOS:A1991FU84500006 ER PT J AU JETTEN, AM AF JETTEN, AM TI GROWTH AND DIFFERENTIATION FACTORS IN TRACHEOBRONCHIAL EPITHELIUM SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Review DE STEM CELLS; TRANSFORMING GROWTH FACTOR-ALPHA; TRANSFORMING GROWTH FACTOR-BETA; INSULIN-LIKE GROWTH FACTOR; RETINOIC ACID; RETINOIDS; RECEPTORS; KERATINOCYTE GROWTH FACTOR; SQUAMOUS DIFFERENTIATION ID RETINOIC ACID RECEPTOR; HAMSTER TRACHEAL EPITHELIUM; INVITRO SQUAMOUS DIFFERENTIATION; PLASMINOGEN-ACTIVATOR INHIBITOR; FETAL LUNG FIBROBLASTS; VITAMIN-A-DEFICIENCY; CARCINOMA CELL-LINE; SERUM-FREE MEDIUM; FACTOR-BETA; FACTOR-I AB The normal tracheobronchial epithelium is continuously renewing itself: cells are lost and replaced by the proliferation and differentiation of stem cells. The proliferation and differentiation of these cells have to be tightly controlled in order to maintain the normal structure of the epithelium. A variety of biological and biochemical processes are involved in controlling the proliferation and differentiation of the tracheobronchial epithelium. Since the trachea and bronchus are comprised of a heterogeneous cell population, interactions between the different cell types are of crucial importance not only in controlling the normal maintenance of this tissue but also in the regulation of repair processes following injury and morphogenesis during lung development. A variety of factors, including several polypeptide growth factors and cytokines, have been identified that regulate positively or negatively the growth and differentiation of tracheobronchial epithelial cells by autocrine or paracrine mechanisms. Retinoids are another group of regulatory factors that appear to play a crucial role in controlling cell proliferation and differentiation in the tracheobronchial epithelium. Recently, many advances have been made in understanding the action of these agents in these cells. Alterations in the balance between growth and differentiation regulatory factors appear to play an important role in several pathophysiological changes such as hyperplasia, fibrosis, and neoplasia. RP JETTEN, AM (reprint author), NIEHS,PULM PATHOBIOL SECT,CELL BIOL SECT,RES TRIANGLE PK,NC 27709, USA. NR 152 TC 71 Z9 73 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUN PY 1991 VL 260 IS 6 BP L361 EP L373 PN 1 PG 13 WC Physiology SC Physiology GA FU841 UT WOS:A1991FU84100072 PM 2058682 ER PT J AU WOLKOWITZ, OM PICKAR, D AF WOLKOWITZ, OM PICKAR, D TI BENZODIAZEPINES IN THE TREATMENT OF SCHIZOPHRENIA - A REVIEW AND REAPPRAISAL SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Review ID PLASMA HOMOVANILLIC-ACID; GAMMA-AMINOBUTYRIC ACID; CENTRAL NERVOUS-SYSTEM; DOUBLE-BLIND; NEUROLEPTIC TREATMENT; PSYCHOTIC DISORDERS; AUDITORY HALLUCINATIONS; ADJUNCTIVE ALPRAZOLAM; DIAZEPAM; GABA AB Objective: Benzodiazepines, either alone or added to neuroleptics, have been studied extensively as treatments for schizophrenia, but no consensus regarding their efficacy has been reached. The authors review the double-blind trails in the literature and relate the findings to the neurobiology of benzodiazepine actions. Method: The clinical review included all double-blind studies through 1989 that could be identified by means of Index Medicus and computer-assisted searches and by the cross-referencing of articles. The findings from the 14 studies of benzodiazepines used alone and the 16 studies of adjunctive therapy are presented separately. Results: The studies reviewed suggest that 1) response is highly variable, and about one-third to one-half of patients improve; 2) benzodiazepines are potentially most useful as adjuncts to neuroleptics in the acute management of psychotic agitation, although actual antipsychotic effects have also been observed in some patients; 3) relatively higher doses of benzodiazepines may be associated with better response; and 4) therapeutic effects, when seen, develop rapidly but diminish after several weeks in some patients. The authors explore the neurobiological bases of benzodiazepine action, which presumably underlie their efficacy in schizophrenia and may help explain the variability of response. Conclusions: Future research on benzodiazepines in the treatment of schizophrenia should focus on features that predict response, the relation of dopamine or other neurotransmitter systems to therapeutic effects, the schizophrenic symptoms most amenable to benzodiazepine treatment, changes in neuroleptic dose during benzodiazepine augmentation, the role of benzodiazepines in maintenance therapy, and the optical characteristics of benzodiazepine treatment. C1 UNIV CALIF SAN FRANCISCO,SCH MED,DEPT PSYCHIAT,SAN FRANCISCO,CA 94143. NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. RI Wolkowitz, Owen/J-6649-2013 OI Wolkowitz, Owen/0000-0003-0655-5042 FU NIMH NIH HHS [MH-43612] NR 103 TC 155 Z9 157 U1 3 U2 4 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 JUN PY 1991 VL 148 IS 6 BP 714 EP 726 PG 13 WC Psychiatry SC Psychiatry GA FN639 UT WOS:A1991FN63900003 PM 1674645 ER PT J AU RANDELL, SH COMMENT, CE RAMAEKERS, FCS NETTESHEIM, P AF RANDELL, SH COMMENT, CE RAMAEKERS, FCS NETTESHEIM, P TI PROPERTIES OF RAT TRACHEAL EPITHELIAL-CELLS SEPARATED BASED ON EXPRESSION OF CELL-SURFACE ALPHA-GALACTOSYL END GROUPS SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID BASAL CELLS; BASEMENT-MEMBRANE; COLUMNAR CELLS; FLOW-CYTOMETRY; DIFFERENTIATION; BINDING; PROLIFERATION; ISOLECTINS; ANTIBODIES; EPIDERMIS AB We used Griffonia (bandeiraea) simplicifolia I (GS I) lectin and flow cytometry to isolate subsets of rat tracheal epithelial cells based on the presence or absence of cell surface alpha-galactosyl end groups. These fractions were designated GS I-positive and -negative, respectively. Ninety-eight percent of the cells in the GS I-positive fraction expressed cell surface alpha-galactosyl end groups; 95% had immunocytochemically detectable keratin 14-related protein (a basal cell marker) and 98% lacked alcian blue-periodic acid-Schiff (AB-PAS)-stained cytoplasmic granules. More than 90% of the GS I-positive cells had a high nuclear-to-cytoplasm ratio, had tonofilaments, and lacked organelles characteristic of other differentiated cell types; they were thus classified as basal cells. In bioassays, the GS I-positive fraction had a colony-forming efficiency greater than or equal to that of native tracheal cell suspensions, and the cells were able to repopulate denuded tracheal grafts with ciliated, secretory, and basal cells. More than 99% of the cells in the GS 1-negative fraction lacked cell surface alpha-galactosyl end groups, 98% did not stain for keratin 14-related protein, 54% had significant numbers of AB-PAS-stained cytoplasmic granules, and 16% were identified as ciliated cells. The GS I-negative fraction had a lower colony-forming efficiency than the GS I-positive fraction but, it too, was able to repopulate denuded tracheal grafts with a complete mucociliary epithelium. These results show that both GS I-positive and -negative cells had the potential to proliferate and differentiate into the major tracheal cell types. C1 STATE UNIV LIMBURG,DEPT MOLEC CELL BIOL,6200 MD MAASTRICHT,NETHERLANDS. RP RANDELL, SH (reprint author), NIEHS,PULM PATHOBIOL & IMMUNOTOXICOL LABS,LPP MD D2-01,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 37 TC 75 Z9 76 U1 0 U2 2 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JUN PY 1991 VL 4 IS 6 BP 544 EP 554 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA FQ017 UT WOS:A1991FQ01700010 PM 1711352 ER PT J AU TRAVIS, WD LINNOILA, RI TSOKOS, MG HITCHCOCK, CL CUTLER, GB NIEMAN, L CHROUSOS, G PASS, H DOPPMAN, J AF TRAVIS, WD LINNOILA, RI TSOKOS, MG HITCHCOCK, CL CUTLER, GB NIEMAN, L CHROUSOS, G PASS, H DOPPMAN, J TI NEUROENDOCRINE TUMORS OF THE LUNG WITH PROPOSED CRITERIA FOR LARGE-CELL NEUROENDOCRINE CARCINOMA - AN ULTRASTRUCTURAL, IMMUNOHISTOCHEMICAL, AND FLOW CYTOMETRIC STUDY OF 35 CASES SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE CARCINOID; ATYPICAL CARCINOID; SMALL-CELL CARCINOMA; NEUROENDOCRINE CARCINOMA; LARGE-CELL NEUROENDOCRINE CARCINOMA; KULCHITSKY CELL CARCINOMA; CUSHINGS SYNDROME; MULTIPLE ENDOCRINE NEOPLASIA ID NEURO-ENDOCRINE NEOPLASMS; HUMAN CHORIONIC-GONADOTROPIN; GASTRIN-RELEASING PEPTIDE; BRONCHIAL CARCINOIDS; CARCINOEMBRYONIC ANTIGEN; INTERMEDIATE FILAMENTS; EXPRESSION; CANCER; ACTH; DIFFERENTIATION AB Based on our review of 35 cases and the literature, we found the spectrum of pulmonary neuroendocrine (NE) tumors to be too broad to fit into the traditional three-category classification scheme of typical carcinoid (TC), atypical carcinoid (AC), and small-cell lung carcinoma (SCLC). We found that a spectrum of high- and low-grade tumors exist between TC and SCLC and that in the past many of these tumors have been called AC. We chose to adhere to Arrigoni's definition of AC, as his original criteria characterized a low-grade tumor. For the higher grade non-small-cell tumors (NSCLC), we propose a fourth category of large-cell neuroendocrine carcinoma (LCNEC), which is characterized by: (a) light microscopic NE appearance; (b) cells of large size, polygonal shape, low nuclear-cytoplasmic ratio (N:C), coarse nuclear chromatin, and frequent nucleoli; (c) high mitotic rate [> 10/10 high-power fields (HPF)] and frequent necrosis; and (d) NE features by immunohistochemistry (IHC) or electron microscopy (EM). Thus, after deciding that a pulmonary NE tumor is high grade, the major diagnostic issue is separation of LCNEC from SCLC. This distinction is based not only on cell size, but on a variety of morphologic features. We studied 20 TC, six AC, five LCNEC, and four SCLC and characterized the clinical, light microscopic, EM, IHC, and flow cytometric features of each type of tumor. We did not find any advantage to IHC, EM, or flow cytometry over light microscopy in the subclassification or prediction of prognosis; however, these methods were useful in characterizing these four types of pulmonary NE tumors and in demonstrating their NE properties. LCNEC must be distinguished from a fifth category pulmonary NE tumor: NSCLC with NE features in which NE differentiation is not evident by light microscopy and must be demonstrated by EM or IHC. Although the prognosis of LCNEC appears to be intermediate between AC and SCLC, larger numbers of patients will be needed to demonstrate significant differences in survival. C1 NICHHD, SURG BRANCH, BETHESDA, MD 20892 USA. NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NIH, WARREN G MAGNUSON CLIN CTR, DEPT DIAGNOST RADIOL, BETHESDA, MD 20892 USA. ARMED FORCES INST PATHOL, DEPT CELLULAR PATHOL, WASHINGTON, DC 20306 USA. USN HOSP, PATHOL LAB, BETHESDA, MD 20814 USA. USN HOSP, NCI, NAVY MED ONCOL BRANCH, BETHESDA, MD 20814 USA. NR 91 TC 502 Z9 526 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUN PY 1991 VL 15 IS 6 BP 529 EP 553 DI 10.1097/00000478-199106000-00003 PG 25 WC Pathology; Surgery SC Pathology; Surgery GA FM530 UT WOS:A1991FM53000003 PM 1709558 ER PT J AU HORAN, MJ AF HORAN, MJ TI ANTIHYPERTENSIVE THERAPY AND ATHEROSCLEROSIS SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE HYPERTENSION; ATHEROSCLEROSIS; ANTIHYPERTENSIVE DRUGS; ATHEROGENESIS ID HYPERTENSIVE PATIENTS; MILD HYPERTENSION; LIPOPROTEINS; CHLORTHALIDONE; CHOLESTEROL; PROPRANOLOL; INDAPAMIDE; EFFICACY; DRUGS; TRIAL AB Hypertension and atherosclerosis make indpendent contributions to the pathogenesis of cardiovascular disease. Diuretics and beta adrenergic blockers, effective antihypertensive medications, exhibit some untoward effects on lipid metabolism, while most other antihypertensive medications tend not to exhibit such effects. In animal models, beta adrenergic blockers, angiotensin converting enzyme (ACE) inhibitors, and calcium antagonists have antiatherogenic effects. A vascular biological approach to therapy for the patient with both hypertension and atherosclerosis is recommended. This includes effective reduction of blood pressure-preferably with agents that do not adversely affect lipid metabolism-and treatment of lipid metabolism disorders. RP HORAN, MJ (reprint author), NHLBI,DIV HEART & VASC DIS,FED BLDG,ROOM 320,7550 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 30 TC 4 Z9 4 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD JUN PY 1991 VL 301 IS 6 BP 402 EP 405 DI 10.1097/00000441-199106000-00010 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA FQ686 UT WOS:A1991FQ68600010 PM 2039028 ER PT J AU FOO, A CARTER, R LAMBROS, C GRAVES, P QUAKYI, I TARGETT, GAT PONNUDURAI, T LEWIS, GE AF FOO, A CARTER, R LAMBROS, C GRAVES, P QUAKYI, I TARGETT, GAT PONNUDURAI, T LEWIS, GE TI CONSERVED AND VARIANT EPITOPES OF TARGET ANTIGENS OF TRANSMISSION-BLOCKING ANTIBODIES AMONG ISOLATES OF PLASMODIUM-FALCIPARUM FROM MALAYSIA SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID MONOCLONAL-ANTIBODIES; SEXUAL STAGE; VACCINE CANDIDATE; IMMUNITY; MALARIA; PROTEIN; BIOSYNTHESIS; PARASITES; MOSQUITO AB Monoclonal antibodies (MAbs) directed against different epitope regions on three sexual stage-specific gamete surface proteins of Plasmodium falciparum, Pfs 25, Pfs 230, and Pfs 48/45, were used to study the genetic diversity of these epitopes among fresh isolates of P. falciparum from Malaysia, using immunofluorescence microscopy (IFA). Among 45 Malaysian isolates, one epitope of Pfs 25, designated region I, showed evidence of variable reactivity with MAbs among different isolates; the Pfs 25 epitope, region II, was universally recognized by MAbs in all isolates. Two apparently distinct epitope regions of Pfs 230 were defined by MAbs, one of which was universally recognized by MAbs among the 45 isolates; the other was conserved in all but three isolates. The epitope regions of gamete-surface protein Pfs 48/45, designated regions I, IIa, IIb, IIc, III, and IV, were examined for reactivity by IFA in 33 isolates. Epitope regions I, IIb, III, and IV were conserved in all isolates; regions IIa and IIc existed in variant forms. C1 UNIV EDINBURGH,ICAPB,DIV BIOL SCI,W MAINS RD,EDINBURGH EH9 3JN,MIDLOTHIAN,SCOTLAND. USA,MED RES UNIT,INST MED RES,KUALA LUMPUR,MALAYSIA. QUEENSLAND INST MED RES,HERSTON,QLD 4006,AUSTRALIA. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. UNIV LONDON LONDON SCH HYG & TROP MED,DEPT PARASITOL,LONDON WC1E 7HT,ENGLAND. CATHOLIC UNIV NIJMEGEN,FAC MED,DEPT MED,NIJMEGEN,NETHERLANDS. OI Graves, Patricia/0000-0002-5215-3901 FU Wellcome Trust NR 24 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JUN PY 1991 VL 44 IS 6 BP 623 EP 631 PG 9 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA GA229 UT WOS:A1991GA22900009 PM 1713424 ER PT J AU GONGGUY, E CRAVENS, RB PATTERSON, TE AF GONGGUY, E CRAVENS, RB PATTERSON, TE TI CLINICAL ISSUES IN MENTAL-HEALTH-SERVICE DELIVERY TO REFUGEES SO AMERICAN PSYCHOLOGIST LA English DT Article ID SOUTHEAST ASIAN REFUGEES; CARE; CHILDREN; ILLNESS C1 US DEPT HHS,OFF REFUGEE HLTH,ROCKVILLE,MD 20852. NIMH,REFUGEE MENTAL HLTH PROGRAM,ROCKVILLE,MD 20857. RP GONGGUY, E (reprint author), UNIV CALIF LOS ANGELES,CTR HLTH SCI,STUDENT PSYCHOL SERV,A3-062,LOS ANGELES,CA 90024, USA. NR 55 TC 57 Z9 57 U1 1 U2 7 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 JUN PY 1991 VL 46 IS 6 BP 642 EP 648 DI 10.1037//0003-066X.46.6.642 PG 7 WC Psychology, Multidisciplinary SC Psychology GA FP693 UT WOS:A1991FP69300008 PM 1952423 ER PT J AU HURD, SS AF HURD, SS TI LUNG HEALTH STUDY - PULMONARY-FUNCTION TESTING SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Editorial Material RP HURD, SS (reprint author), NHLBI,DIV LUNG DIS,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD JUN PY 1991 VL 143 IS 6 BP 1211 EP 1211 PG 1 WC Respiratory System SC Respiratory System GA FP897 UT WOS:A1991FP89700002 PM 2048801 ER PT J AU DOBSON, GP VEECH, RL HOEGER, U PASSONNEAU, JV AF DOBSON, GP VEECH, RL HOEGER, U PASSONNEAU, JV TI ENZYMATIC DETERMINATION OF TOTAL CO2 IN FREEZE-CLAMPED ANIMAL-TISSUES AND PLASMA SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID BRAIN RP DOBSON, GP (reprint author), NIAAA,METAB & MOLEC BIOL LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 25 TC 6 Z9 6 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JUN PY 1991 VL 195 IS 2 BP 232 EP 237 DI 10.1016/0003-2697(91)90322-K PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA FP885 UT WOS:A1991FP88500007 PM 1750672 ER PT J AU HEEGAARD, NHH BJERRUM, OJ AF HEEGAARD, NHH BJERRUM, OJ TI AFFINITY ELECTROPHORESIS USED FOR DETERMINATION OF BINDING CONSTANTS FOR ANTIBODY ANTIGEN REACTIONS SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID MONOCLONAL-ANTIBODIES; DEXTRAN C1 NIMH,NEUROSCI CTR ST ELIZABETHS,BIOCHEM GENET LAB,WASHINGTON,DC 20032. NOVO NORDISK,DK-2880 BAGSVAERD,DENMARK. UNIV COPENHAGEN,PROT LAB,DK-2200 COPENHAGEN,DENMARK. NR 28 TC 15 Z9 15 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JUN PY 1991 VL 195 IS 2 BP 319 EP 326 DI 10.1016/0003-2697(91)90337-S PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA FP885 UT WOS:A1991FP88500022 PM 1750687 ER PT J AU BRYANT, DK ORLANDO, RC FENSELAU, C SOWDER, RC HENDERSON, LE AF BRYANT, DK ORLANDO, RC FENSELAU, C SOWDER, RC HENDERSON, LE TI 4-SECTOR TANDEM MASS-SPECTROMETRIC ANALYSIS OF COMPLEX-MIXTURES OF PHOSPHATIDYLCHOLINES PRESENT IN A HUMAN-IMMUNODEFICIENCY-VIRUS PREPARATION SO ANALYTICAL CHEMISTRY LA English DT Article ID FAST-ATOM-BOMBARDMENT; PHOSPHOLIPIDS; DESORPTION; IONIZATION; LIPIDS AB A number of phosphatidylcholines have been isolated from an HIV-1/MN preparation by reversed-phase high-performance liquid chromatography (HPLC) and analyzed by fast atom bombardment mass spectrometry (FABMS), FABMS/MS, and FABMS/MS/MS in both positive- and negative-ion modes. Negative-ion FABMS/MS with high-energy collisions was used to identify the length of the acyl groups and the degree of saturation, as well as their position on the glyceride group. FABMS/MS in the positive-ion mode was used to identify the polar head group. Negative-ion FABMS/MS/MS was used to locate positions of double bonds in acyl groups. We find that four-sector tandem mass spectrometry with high-energy collisional activation provides qualitative analysis of viral phosphatidyl lipids in considerable detail, as well as semi-quantitative information. Approximate quantitation of the phosphatidylcholine content of the HIV-1/MN preparation by measuring relative peak heights of molecular ions in FABMS reveals an array of phosphatidylcholines consistent with that found in human erythrocytes, indicating the likely source of lipids in the viral membrane to be the host cell membrane. C1 PRI DYN CORP,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. RP BRYANT, DK (reprint author), UNIV MARYLAND,DEPT CHEM & BIOCHEM,CATONSVILLE,MD 21228, USA. NR 33 TC 44 Z9 44 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JUN 1 PY 1991 VL 63 IS 11 BP 1110 EP 1114 DI 10.1021/ac00011a010 PG 5 WC Chemistry, Analytical SC Chemistry GA FN812 UT WOS:A1991FN81200012 PM 1883068 ER PT J AU PROSCHAN, M AF PROSCHAN, M TI A NOTE ON BLACKWELL AND HODGES (1957) AND DIACONIS AND GRAHAM (1981) SO ANNALS OF STATISTICS LA English DT Note DE RANDOM ALLOCATION; RETURNS TO THE ORIGIN OF A RANDOM WALK; SELECTION BIAS ID SEQUENTIAL EXPERIMENTS AB The papers of Blackwell and Hodges (1957) and Diaconis and Graham (1981) contain an error concerning the asymptotic distribution of the number of returns to the origin of a constrained random walk. The correct distribution is given. C1 NHLBI,BETHESDA,MD 20892. NR 4 TC 1 Z9 1 U1 1 U2 1 PU INST MATHEMATICAL STATISTICS PI HAYWARD PA IMS BUSINESS OFFICE-SUITE 6 3401 INVESTMENT BLVD, HAYWARD, CA 94545 SN 0090-5364 J9 ANN STAT JI Ann. Stat. PD JUN PY 1991 VL 19 IS 2 BP 1106 EP 1108 DI 10.1214/aos/1176348144 PG 3 WC Statistics & Probability SC Mathematics GA FU114 UT WOS:A1991FU11400036 ER PT J AU CRITTENDEN, MD ROBERTS, CS ROSA, L VATSIA, SK KATZ, D CLARK, RE SWAIN, JA AF CRITTENDEN, MD ROBERTS, CS ROSA, L VATSIA, SK KATZ, D CLARK, RE SWAIN, JA TI BRAIN PROTECTION DURING CIRCULATORY ARREST SO ANNALS OF THORACIC SURGERY LA English DT Article ID HYPOTHERMIA; PERFUSION; SURGERY; DAMAGE AB Previous nuclear magnetic resonance studies in this laboratory have shown a beneficial biochemical effect of antegrade cerebroplegia (CP-A) during hypothermic circulatory arrest. This study compared CP-A with other methods of cerebral protection during hypothermic circulatory arrest to assess the clinical utility of this technique. Twenty-three sheep were divided into four groups: systemic hypothermia alone (SYST) and systemic hypothermia combined with external cranial cooling (EXTNL), retrograde cerebroplegia (CP-R), or CP-A. Cardiopulmonary bypass was started, and the sheep were cooled to 15-degrees-C and subjected to 2 hours of circulatory arrest. Cardiopulmonary bypass was restarted, and the animals were rewarmed and weaned from cardiopulmonary bypass. Serial neurological examinations were performed and hourly scores assigned until the animals were extubated. Postanesthetic neurological scores improved in all groups throughout the 6-hour recovery period except the CP-R group. The improvement over time for these scores was similar for the EXTNL and CP-A groups and significantly better than for the SYST or CP-R groups (p = 0.004). The CP-A group had 5 of 7 animals with deficit-free survival despite the similarity in recovery of baseline brainstem function. We conclude that both antegrade infusion of cerebroplegia and external cranial cooling confer distinct cerebroprotective effects after a protracted period of hypothermic circulatory arrest when compared with the other methods studied. C1 NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. NHLBI,SURG BRANCH,BETHESDA,MD 20892. NR 20 TC 48 Z9 50 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUN PY 1991 VL 51 IS 6 BP 942 EP 947 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA FQ352 UT WOS:A1991FQ35200014 PM 2039323 ER PT J AU PATEL, SS SZEBENI, J WAHL, LM WEINSTEIN, JN AF PATEL, SS SZEBENI, J WAHL, LM WEINSTEIN, JN TI DIFFERENTIAL INHIBITION OF 2'-DEOXYCYTIDINE SALVAGE AS A POSSIBLE MECHANISM FOR POTENTIATION OF THE ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS ACTIVITY OF 2',3'-DIDEOXYCYTIDINE BY DIPYRIDAMOLE SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Note ID CENTRIFUGAL ELUTRIATION CCE; MONOCYTE-ENRICHED FRACTIONS; MONONUCLEAR CELL SUBSETS; 3'-AZIDO-3'-DEOXYTHYMIDINE; MACROPHAGES; PERMEATION; INVITRO; 2',3'-DIDEOXYNUCLEOSIDES; INFECTIVITY; NUCLEOSIDES AB Dipyridamole, a commonly used coronary vasodilator and antithrombotic drug, was recently shown to potentiate the activity of 3'-azido-3'-deoxythymidine and 2',3'-dideoxycytidine against the human immunodeficiency virus type 1 (HIV-1) in human monocyte-macrophages in vitro. We report in the present paper that in uninfected monocyte-macrophages dipyridamole significantly inhibits cellular salvage of [H-3]deoxycytidine, whereas it does not affect the salvage of [H-3]dideoxycytidine. Similar differential inhibition by dipyridamole of the salvage of thymidine, as opposed to 3'-azido-3'-deoxythymidine, was reported previously (G. V. Betageri, J. Szebeni, K. Hung, S. S. Patel, L. M. Wahl, M. Corcoran, and J. N. Weinstein, Biochem. Pharmacol. 40:867-870, 1990). Taken together, these observations suggest that inhibition of the salvage of competing physiological nucleosides may explain or contribute to the potentiating effect of dipyridamole on these antiviral dideoxynucleoside drugs. C1 NCI, BETHESDA, MD 20892 USA. NIDR, BETHESDA, MD 20892 USA. NR 24 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 1991 VL 35 IS 6 BP 1250 EP 1253 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA FP916 UT WOS:A1991FP91600047 PM 1656858 ER PT J AU MANJI, HK HSIAO, JK RISBY, ED RUDORFER, MV POTTER, WZ OLIVER, J AF MANJI, HK HSIAO, JK RISBY, ED RUDORFER, MV POTTER, WZ OLIVER, J TI THE MECHANISMS OF ACTION OF LITHIUM .1. EFFECTS ON SEROTONINERGIC AND NORADRENERGIC SYSTEMS IN NORMAL SUBJECTS SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Review ID LONG-TERM LITHIUM; PERFORMANCE LIQUID-CHROMATOGRAPHY; NEURO-ENDOCRINE RESPONSES; MAJOR AFFECTIVE-DISORDERS; MANIC-DEPRESSIVE PATIENTS; PLATELET 5-HT RECEPTORS; RAT-BRAIN; CEREBROSPINAL-FLUID; ELECTROCHEMICAL DETECTION; CATECHOLAMINE METABOLISM AB The effects of 2 weeks of lithium carbonate administration at therapeutic plasma levels were examined in 11 normal volunteers. Serotoninergic function before and after lithium administration was assessed using low-dose intravenous clomipramine hydrochloride challenge, while urinary and plasma metabolites of norepinephrine (NE) were used to assess noradrenergic systems. Long-term lithium administration in normal subjects did not significantly or consistently enhance serotonin-mediated neuroendocrine responses but did increase measures related to neuronal release of NE. No statistically significant effects of lithium on prolactin, corticotropin, or cortisol responses to serotoninergic challenge could be detected. The probability of a type II error was assessed, and a doubling of prolactin level was unlikely to have been missed, although more modest increases (< 75%) could have been overlooked. After 2 weeks of lithium administration, there were significant increase in 24-hours urinary excretion of NE, normetanephrine, and fractional NE release, compatible with increased neuronal release of NE and a lithium-induced subsensitivity in alpha-2-adrenergic receptor function. These changes were not statistically significant after 1 week of administration, suggesting that increased NE release is characteristic of long-rather than short-term lithium administration. Since previous reports have demonstrated enhanced prolactin responses after short-but not long-term lithium use, the present study points to temporal specificity in lithium's effects on both serotoninergic and noradrenergic function. Lithium's effects on NE release were consistent but small (a 16% increase), while its effects on serotoninergic responses were larger (a 50% increase in prolactin responses) but quite inconsistent, suggesting that neither of these systems is the primary site of action of lithium. C1 NIMH,EXPTL THERAPEUT BRANCH,CLIN PHARMACOL SECT,ROOM 2D46,BLDG 10,BETHESDA,MD 20892. EMORY UNIV,SCH MED,DEPT PSYCHIAT,ATLANTA,GA 30322. NR 111 TC 57 Z9 57 U1 2 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 JUN PY 1991 VL 48 IS 6 BP 505 EP 512 PG 8 WC Psychiatry SC Psychiatry GA FQ353 UT WOS:A1991FQ35300001 PM 1645513 ER PT J AU RISBY, ED HSIAO, JK MANJI, HK BITRAN, J MOSES, F ZHOU, DF POTTER, WZ AF RISBY, ED HSIAO, JK MANJI, HK BITRAN, J MOSES, F ZHOU, DF POTTER, WZ TI THE MECHANISMS OF ACTION OF LITHIUM .2. EFFECTS ON ADENYLATE-CYCLASE ACTIVITY AND BETA-ADRENERGIC-RECEPTOR BINDING IN NORMAL SUBJECTS SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Review ID RAT CEREBRAL-CORTEX; INOSITOL PHOSPHOLIPID HYDROLYSIS; CYCLIC-AMP ACCUMULATION; PROTEIN KINASE-C; MESSENGER SIGNAL AMPLIFICATION; AFFECTIVE-DISORDERS; SEROTONIN RELEASE; ANTIDEPRESSANT RESPONSE; TRYPTOPHAN TRANSPORT; DEPRESSED-PATIENTS AB As part of a study of the effects of lithium carbonate on neurochemical function in man, platelet and lymphocyte adenylate cyclase activity and lymphocyte beta-adrenergic receptor binding characteristics were determined before and after 2 weeks of lithium treatment in 10 normal volunteers. Lithium had differential effects on platelet and lymphocyte adenylate cyclase activity. In platelets, basal and stimulated (guanyl imidodiphosphate [Gpp[NH]p] or cesium fluoride) adenylate cyclase activity was significantly augmented by lithium treatment. By contrast, in lymphocytes, Gpp(NH)p- and cesium fluoride-stimulated adenylate cyclase activity was unaffected, while basal activity was decreased modestly after lithium. These results are consistent with preclinical studies that suggest that lithium's effects on adenylate cyclase activity are specific with respect to tissue and brain region and that lithium may interfere with guanine nucleotide binding (G) protein function. Lithium treatment significantly increased the ratio of low- to high-affinity dissociation constants for agonist displacement of antagonist binding to lymphocyte beta-adrenergic receptors (thought to reflect coupling between the beta-adrenergic adrenergic receptor and stimulatory G protein). Lithium had significant effects on measures associated with signal transduction that might be contrasted to its more subtle effects on neuronal function (norepinephrine release) and neuroendocrine systems (responses to serotoninergic challenge) in these same subjects (reported in a companion article). Lithium's primary site of action may be on signal transduction mechanisms. These effects subsequently may be manifested in changes in neurotransmitter fuction that may be important to lithium's mood-stabilizing actions. C1 NIMH,EXPTL THERAPEUT BRANCH,CLIN PHARMACOL SECT,ROOM 2D46,BLDG 10,BETHESDA,MD 20892. BEIJING MED UNIV,INST MENTAL HLTH,BEIJING,PEOPLES R CHINA. NIAA,BETHESDA,MD. EMORY UNIV,SCH MED,DEPT PSYCHIAT,ATLANTA,GA 30322. NR 109 TC 93 Z9 93 U1 2 U2 3 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 JUN PY 1991 VL 48 IS 6 BP 513 EP 524 PG 12 WC Psychiatry SC Psychiatry GA FQ353 UT WOS:A1991FQ35300002 PM 1645514 ER PT J AU LESCH, KP HOH, A DISSELKAMPTIETZE, J WIESMANN, M OSTERHEIDER, M SCHULTE, HM AF LESCH, KP HOH, A DISSELKAMPTIETZE, J WIESMANN, M OSTERHEIDER, M SCHULTE, HM TI 5-HYDROXYTRYPTAMINE-1A RECEPTOR RESPONSIVITY IN OBSESSIVE-COMPULSIVE DISORDER - COMPARISON OF PATIENTS AND CONTROLS SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; 5-HT1A RECEPTOR; CLOMIPRAMINE TREATMENT; HYPOTHERMIC RESPONSE; SEROTONIN FUNCTION; ANTIDEPRESSANT TREATMENTS; CORTICOSTERONE SECRETION; PARAVENTRICULAR NUCLEUS; ELECTROCONVULSIVE SHOCK; ADENYLATE-CYCLASE AB To evaluate 5-hydroxytryptamine1A receptor responsivity in obsessive-compulsive disorder, we examined hypothermic, neuroendocrine, and behavioral responses to the selective 5-hydroxytryptamine1A receptor ligand ipsapirone in patients with primary obsessive-compulsive disorder and healthy controls. Twelve patients and 22 controls received a single dose of ipsapirone, 0.3 mg/kg, or placebo under double-blind, random assignment conditions. Ipsapirone induced hypothermia and release of corticotropin and cortisol but had no effect on behavior, including obsessive or compulsive symptoms. Thermoregulatory and neuroendocrine responses to ipsapirone were not consistently different between healthy controls and patients with obsessive-compulsive disorder. These results provide no direct support for the hypothesis that a serotonergic dysfunction related to 5-hydroxytryptamine1A receptors may be linked to the pathophysiologic characteristics of obsessive-compulsive disorder and point to the need for the evaluation of other 5-hydroxytryptamine receptor subtypes. Future studies of the responsivity of 5-hydroxytryptamine1A receptors to direct-acting ligands, such as ipsapirone, should facilitate assessment of the integrity of the 5-hydroxytryptamine system and its involvement in antiobsessional drug effects. C1 UNIV WURZBURG,DEPT PSYCHIAT,W-8700 WURZBURG,GERMANY. UNIV KIEL,DEPT MED 1,W-2300 KIEL 1,GERMANY. RP LESCH, KP (reprint author), NIMH,CTR CLIN,CLIN SCI LAB,10-3D41,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 79 TC 68 Z9 68 U1 4 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 JUN PY 1991 VL 48 IS 6 BP 540 EP 547 PG 8 WC Psychiatry SC Psychiatry GA FQ353 UT WOS:A1991FQ35300005 PM 1674853 ER PT J AU KAYE, WH GWIRTSMAN, HE GEORGE, DT EBERT, MH AF KAYE, WH GWIRTSMAN, HE GEORGE, DT EBERT, MH TI ALTERED SEROTONIN ACTIVITY IN ANOREXIA-NERVOSA AFTER LONG-TERM WEIGHT RESTORATION - DOES ELEVATED CEREBROSPINAL-FLUID 5-HYDROXYINDOLEACETIC ACID LEVEL CORRELATE WITH RIGID AND OBSESSIVE BEHAVIOR SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID COMPULSIVE DISORDER; MONOAMINE METABOLITES; CLOMIPRAMINE TREATMENT; EATING DISORDERS; AMINE METABOLITES; CSF 5-HIAA; BRAIN; BULIMIA; WOMEN; PERSONALITY AB To avoid the confounding influences of mainutrition or weight loss, we studied patients with anorexia nervosa at normal weight and stable dietary intake. Compared with 15 controls, 17 long-term weight-restored anorectic subjects had elevated concentrations of cerebrospinal fluid 5-hydroxyindoleacetic acid, the major serotonin metabolite, whereas levels of cerebrospinal fluid homovanillic acid, the major dopamine metabolite, were normal. Elevated levels of cerebrospinal fluid 5-hydroxyindoleacetic acid may indicate increased serotonin activity. Such activity could contribute to pathological feeding behavior. Most importantly, this study raises the question as to whether increased cerebrospinal fluid 5-hydroxyindoleacetic acid levels are associated with overly inhibited, anxious, or obsessive traits. C1 NIAAA,BETHESDA,MD. VANDERBILT UNIV,MED CTR,SCH MED,DEPT PSYCHIAT,NASHVILLE,TN 37232. NIMH,PSYCHOL LAB,BETHESDA,MD 20892. NIMH,PSYCHOPATHOL LAB,BETHESDA,MD 20892. NR 82 TC 210 Z9 213 U1 3 U2 6 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 JUN PY 1991 VL 48 IS 6 BP 556 EP 562 PG 7 WC Psychiatry SC Psychiatry GA FQ353 UT WOS:A1991FQ35300007 PM 1710099 ER PT J AU FOX, PC ATKINSON, JC MACYNSKI, AA WOLFF, A KUNG, DS VALDEZ, IH JACKSON, W DELAPENHA, RA SHIROKY, J BAUM, BJ AF FOX, PC ATKINSON, JC MACYNSKI, AA WOLFF, A KUNG, DS VALDEZ, IH JACKSON, W DELAPENHA, RA SHIROKY, J BAUM, BJ TI PILOCARPINE TREATMENT OF SALIVARY-GLAND HYPOFUNCTION AND DRY MOUTH (XEROSTOMIA) SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID FLOW-RATE AB We studied the effects of pilocarpine hydrochloride, a parasympathomimetic agent, on major salivary gland output and subjective responses in 31 patients with salivary hypofunction. Pilocarpine hydrochloride (5-mg capsules, three times daily) was given for 5 months and a placebo was randomly assigned for 1 month in a double-blind fashion. Objective measurements of major salivary gland output, subjective impressions of oral moisture, treatment-related side effects, and a number of physiologic measures were assessed monthly. Pilocarpine significantly increased salivary output in 21 of the 31 patients. Subjective improvement in the feeling of oral dryness, speaking, chewing, and swallowing were reported by 27 individuals. Side effects, while common, generally were mild and tolerable. There were no significant alterations in cardiovascular or other physiologic measures. We conclude that pilocarpine is an effetive and safe treatment for salivary gland hypofunction and xerostomia in selected patients. The increase in major gland output provides beneficial natural secretions and relief of oral dryness. C1 COLUMBIA UNIV,SCH DENT & ORAL SURG,NEW YORK,NY 10027. RP FOX, PC (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,ROOM 1N-113,BETHESDA,MD 20892, USA. NR 12 TC 123 Z9 124 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN PY 1991 VL 151 IS 6 BP 1149 EP 1152 DI 10.1001/archinte.151.6.1149 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA FQ681 UT WOS:A1991FQ68100014 PM 2043017 ER PT J AU LEVIN, HS SAYDJARI, C EISENBERG, HM FOULKES, M MARSHALL, LF RUFF, RM JANE, JA MARMAROU, A AF LEVIN, HS SAYDJARI, C EISENBERG, HM FOULKES, M MARSHALL, LF RUFF, RM JANE, JA MARMAROU, A TI VEGETATIVE STATE AFTER CLOSED-HEAD INJURY - A TRAUMATIC COMA DATA-BANK REPORT SO ARCHIVES OF NEUROLOGY LA English DT Article ID IMPAIRED CONSCIOUSNESS; PROGNOSIS AB To elucidate the clinical course of the vegetative state after severe closed-head injury, the Traumatic Coma Data Bank was analyzed for outcome at the time of discharge from the hospital and after follow-up intervals ranging up to 3 years after injury. Of 650 patients with closed-head injury available for analysis, 93 (14%) were discharged in a vegetative state. In comparison with conscious survivors, patients in a vegetative state sustained more severe closed-head injury as reflected by the Glasgow Coma Scale scores and pupillary findings and more frequently had diffuse injury complicated by swelling or shift in midline structures. Of 84 patients in a vegetative state who provided follow-up data, 41% became conscious by 6 months, 52% regained consciousness by 1 year, and 58% recovered consciousness within the 3-year follow-up interval. A logistic regression failed to identify predictors of recovery from the vegetative state. C1 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT NEUROSURG,RICHMOND,VA 23298. UNIV CALIF SAN DIEGO,DIV NEUROSURG,LA JOLLA,CA 92093. UNIV TEXAS,MED BRANCH,DIV NEUROSURG,GALVESTON,TX 77550. NIH,OFF BIOMETRY,BETHESDA,MD 20892. UNIV VIRGINIA,DEPT NEUROSURG,CHARLOTTESVILLE,VA 22903. FU NINDS NIH HHS [N01-NS-3-2339, N01-NS-3-2340, N01-NS-3-2341] NR 14 TC 97 Z9 101 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUN PY 1991 VL 48 IS 6 BP 580 EP 585 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA FP881 UT WOS:A1991FP88100006 PM 2039378 ER PT J AU LEVY, SM HERBERMAN, RB LIPPMAN, M DANGELO, T LEE, J AF LEVY, SM HERBERMAN, RB LIPPMAN, M DANGELO, T LEE, J TI IMMUNOLOGICAL AND PSYCHOSOCIAL PREDICTORS OF DISEASE RECURRENCE IN PATIENTS WITH EARLY-STAGE BREAST-CANCER SO BEHAVIORAL MEDICINE LA English DT Article DE BREAST CANCER; MOOD; NATURAL KILLER CELLS; SOCIAL SUPPORT ID KILLER-CELL-ACTIVITY; RECEPTOR STATUS; PROGNOSTIC-SIGNIFICANCE; ESTROGEN-RECEPTOR; CYTO-TOXICITY; TUMOR; SURVIVAL; STRESS AB Ninety women with recently diagnosed stage I or stage II breast cancer who had been admitted to the NIH Clinical Center and were participating in a randomized trial were entered onto this behavioral immunology protocol. Patients were immunologically and psychosocially assessed at baseline (approximately 5 days after surgery) and again at 3 and 15 months post surgery. All of the patients were followed up for a minimum of 5 years, and 60% of the patients were followed for 7 years or longer. Twenty-nine women in the study group reported disease recurrences over the entire follow-up period. Causal path modeling statistical techniques showed that natural killer (NK) cell activity was a strong predictor of disease outcome when the outcome variable was defined as recurrence v nonrecurrence of disease (chi-2 =6.9, p < .001). Higher NK cell activity at follow-up predicted disease-free survival over the follow-up period. When the disease outcome variable was operationally defined as time to recurrent disease, the psychosocial factors were more strongly predictive of the rate of disease progression for those who had a recurrence (chi-2 = - 4.1, p < .01), but NK cell activity was seemingly less relevant in this latter case. Overall, these findings suggest that including mood and potentially relevant immunological variables, along with important biological prognostic variables, in multivariate and prospective models such as those examined in this study, potentially contributes more to the explanation of greater outcome variance of early-stage breast cancer than has been believed in the past. C1 PITTSBURGH CANC INST,PITTSBURGH,PA. GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. RP LEVY, SM (reprint author), UNIV PITTSBURGH,PSYCHIAT,200 MEYRAN AVE,2ND FLOOR,PITTSBURGH,PA 15213, USA. NR 39 TC 112 Z9 113 U1 1 U2 7 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 SN 0896-4289 J9 BEHAV MED JI Behav. Med. PD SUM PY 1991 VL 17 IS 2 BP 67 EP 75 PG 9 WC Behavioral Sciences; Psychiatry SC Behavioral Sciences; Psychiatry GA FQ995 UT WOS:A1991FQ99500004 PM 1878611 ER PT J AU IWAHASHI, H PARKER, CE MASON, RP TOMER, KB AF IWAHASHI, H PARKER, CE MASON, RP TOMER, KB TI RADICAL ADDUCTS OF NITROSOBENZENE AND 2-METHYL-2-NITROSOPROPANE WITH 12,13-EPOXYLINOLEIC ACID RADICAL, 12,13-EPOXYLINOLENIC ACID RADICAL AND 14,15-EPOXYARACHIDONIC ACID RADICAL - IDENTIFICATION BY HPLC EPR AND LIQUID-CHROMATOGRAPHY THERMOSPRAY MS SO BIOCHEMICAL JOURNAL LA English DT Article ID ELECTRON-SPIN-RESONANCE; CENTERED FREE-RADICALS; LINOLEIC-ACID; FATTY-ACIDS; SOYBEAN LIPOXYGENASE-1; CARBON-TETRACHLORIDE; ANAEROBIC REACTION; TRAPPED RADICALS; HYDROPEROXIDE; HEMATIN AB Linoleic acid-derived radicals, which are formed in the reaction of linoleic acid with soybean lipoxygenase, were trapped with nitrosobenzene and the resulting radical adducts were analysed by h.p.l.c.-e.p.r. and liquid chromatography-thermospray-m.s. Three nitrosobenzene radical adducts (peaks I, II and III) were detected; these gave the following parent ion masses: 402 for peak I, 402 for peak II, and 386 for peak III. The masses of peaks I and II correspond to the linoleic acid radicals with one more oxygen atom [L(O).]. The radicals are probably carbon-centered, because the use of O-17(2) did not result in an additional hyperfine splitting. Computer simulation of the peak I radical adduct e.p.r. spectrum also suggested that the radical is carbon-centred. The peak I radical was also detected in the reaction of 13-hydroperoxylinoleic acid with FeSO4. From the above results, peak I is probably the 12,13-epoxylinoleic acid radical. An h.p.l.c.-e.p.r. experiment using [9,10,12,13-H-2(4)]linoleic acid suggested that the 12,13-epoxylinoleic acid radical is a C-9-centred radical. Peak II is possibly an isomer of peak I. Peak III, which was observed in the reaction mixture without soybean lipoxygenase, corresponds to a linoleic acid radical (L.). The 12,13-epoxylinoleic acid radical, 12,13-epoxylinolenic acid radical and 14,15-epoxyarachidonic acid radical were also detected in the reactions of linoleic acid, linolenic acid and arachidonic acid respectively, with soybean lipoxygenase using nitrosobenzene and 2-methyl-2-nitrosopropane as spin-trapping agents. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. RI Tomer, Kenneth/E-8018-2013 NR 37 TC 41 Z9 42 U1 0 U2 2 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUN 1 PY 1991 VL 276 BP 447 EP 453 PN 2 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FR342 UT WOS:A1991FR34200025 PM 1646600 ER PT J AU KISS, Z RAPP, UR PETTIT, GR ANDERSON, WB AF KISS, Z RAPP, UR PETTIT, GR ANDERSON, WB TI PHORBOL ESTER AND BRYOSTATIN DIFFERENTIALLY REGULATE THE HYDROLYSIS OF PHOSPHATIDYLETHANOLAMINE IN HA-RAS-ONCOGENE AND RAF-ONCOGENE-TRANSFORMED NIH 3T3 CELLS SO BIOCHEMICAL JOURNAL LA English DT Article ID PROTEIN-KINASE-C; SUB-CELLULAR DISTRIBUTION; PHOSPHATIDYLCHOLINE BREAKDOWN; CARRYING RETROVIRUS; PHOSPHOLIPASE-D; KIDNEY CELLS; FIBROBLASTS; ACTIVATION; HL-60; HEART AB Previously it was reported that transformation of NIH 3T3 fibroblast by the Ha-ras, v-src, v-fms, and A-raf oncogenes decreased the stimulatory effects of phorbol 12-myristate 13-acetate (PMA; 'TPA'), an activator of protein kinase C (PKC), on the phosphorylation of an endogenous 80 kDa substrate and on Rb-86 uptake [Wolfman, Wingrove, Blackshear & Macara (1987) J. Biol. Chem. 262, 16546-16552], as well as on sphingomyelin synthesis [Kiss, Rapp & Anderson (1988) FEBS Lett. 240, 221-226]. Here, we investigated how transformation affects the PMA-stimulated hydrolysis of phosphatidylethanolamine (PtdEtn), a recently characterized mechanism which may contribute to the generation of the second messengers phosphatidic acid and 1,2-diacylglycerol. The effects of PMA were compared with those of bryostatin, a non-tumour-promoter activator of PKC. Transformation of NIH 3T3 cells with Ha-ras, v-raf, or A-raf enhanced the stimulatory effect of PMA on the phospholipase D-mediated hydrolysis of PtdEtn. On the other hand, the effects of bryostatin on PtdEtn hydrolysis were only slightly increased, if at all, in cells transformed with these oncogenes. In crude membrane preparations isolated from these transformed cells, PMA, but not bryostatin, enhanced the combined stimulatory effects of ATP and the GTP analogue guanosine 5'-[gamma-thio]triphosphate on phospholipase D-mediated PtdEtn hydrolysis. The PKC inhibitor 1-(5-isoquinolinesulphonyl)-2-methylpiperazine inhibited the stimulatory effect of PMA only in intact cells. These results indicate that transformation of cells by certain oncogenes differentially affects phospholipase D-mediated hydrolysis of PtdEtn induced by PMA and bryostatin, suggesting that the action of PMA might involve two different mechanisms. C1 UNIV MINNESOTA,HORMEL INST,AUSTIN,MN 55912. NCI,FREDERICK CANC RES FACIL,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. ARIZONA STATE UNIV,CANC RES INST,TEMPE,AZ 85287. ARIZONA STATE UNIV,DEPT CHEM,TEMPE,AZ 85287. RP KISS, Z (reprint author), NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892, USA. NR 39 TC 26 Z9 26 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUN 1 PY 1991 VL 276 BP 505 EP 509 PN 2 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FR342 UT WOS:A1991FR34200033 PM 2049075 ER PT J AU MOLCHAN, SE LAWLOR, BA HILL, JL MARTINEZ, RA DAVIS, CL MELLOW, AM RUBINOW, DR SUNDERLAND, T AF MOLCHAN, SE LAWLOR, BA HILL, JL MARTINEZ, RA DAVIS, CL MELLOW, AM RUBINOW, DR SUNDERLAND, T TI CSF MONOAMINE METABOLITES AND SOMATOSTATIN IN ALZHEIMERS-DISEASE AND MAJOR DEPRESSION SO BIOLOGICAL PSYCHIATRY LA English DT Article ID CEREBROSPINAL-FLUID; SENILE DEMENTIA; CEREBRAL-CORTEX; 5-HYDROXYINDOLEACETIC ACID; HOMOVANILLIC-ACID; RECEPTOR CHANGES; NEURONS; SCALE; IMMUNOREACTIVITY; MELANCHOLIA AB Decreased cerebrospinal fluid (CSF), somatostatinlike immunoreactivity (SLI) and alterations in the CSF monamine metabolites 3-methoxy-4-hydroxyphenylethylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) have been reported in patients with probable Alzheimer's disease (AD) and in patients with major depression. In this study, we found CSF SLI to be significantly lower in a large group of AD patients (n = 60) and in a group of age-matched patients with major depression (n = 18) as compared with normal controls (n = 12). Mean CSF, MHPG, 5-HIAA, and HVA levels were not significantly different among diagnostic groups. Within a group of "depressed" AD patients, CSF levels of 5-HIAA showed a significant positive correlation (p = 0.03) with CSF SLI; a similar relationship was found within the group of patients with major depression. Further exploration of the relationship between the somatostatin and serotonin systems may provide clues as to how neuropeptides interact with monoamine neurotransmitters and what role they have in depression. C1 CUNY MT SINAI SCH MED,DEPT PSYCHIAT,DIV GEROPSYCHIAT,NEW YORK,NY 10029. UNIV MICHIGAN,MED CTR,DEPT PSYCHIAT,ANN ARBOR,MI 48109. NIMH,BIOL PSYCHIAT BRANCH,BEHAV ENDOCRINOL SECT,BETHESDA,MD 20892. RP MOLCHAN, SE (reprint author), NIMH,CTR CLIN,CLIN SCI LAB,GERIATR PSYCHOPHARMACOL UNIT,10-3D41,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 43 TC 37 Z9 37 U1 0 U2 1 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 JUN 1 PY 1991 VL 29 IS 11 BP 1110 EP 1118 DI 10.1016/0006-3223(91)90253-I PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA FT221 UT WOS:A1991FT22100008 PM 1714776 ER PT J AU ADINOFF, B MARTIN, PR ECKARDT, MJ BONE, GHA GOLD, PW LINNOILA, M AF ADINOFF, B MARTIN, PR ECKARDT, MJ BONE, GHA GOLD, PW LINNOILA, M TI PITUITARY-ADRENAL RESPONSES TO OCRH AND CENTRAL NEUROPEPTIDE LEVELS IN ALCOHOL AMNESTIC DISORDER SO BIOLOGICAL PSYCHIATRY LA English DT Note ID CORTICOTROPIN-RELEASING HORMONE C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NIAAA,DICBR,CLIN STUDIES LAB,BETHESDA,MD 20892. RI Martin, Peter/A-7738-2008 NR 8 TC 4 Z9 4 U1 0 U2 0 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 JUN 1 PY 1991 VL 29 IS 11 BP 1153 EP 1155 DI 10.1016/0006-3223(91)90257-M PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA FT221 UT WOS:A1991FT22100012 PM 1651774 ER PT J AU DINSE, GE AF DINSE, GE TI CONSTANT RISK DIFFERENCES IN THE ANALYSIS OF ANIMAL TUMORIGENICITY DATA SO BIOMETRICS LA English DT Article DE ANIMAL EXPERIMENT; CARCINOGENICITY BIOASSAY; ED01 STUDY; INCIDENCE; LETHALITY; OCCULT TUMOR; RISK DIFFERENCE; RISK RATIO; SURVIVAL SACRIFICE EXPERIMENT; TUMORIGENICITY STUDY ID SURVIVAL SACRIFICE EXPERIMENTS; NONPARAMETRIC-ESTIMATION; EM ALGORITHM; CARCINOGENESIS EXPERIMENTS; DEATH; ONSET; PREVALENCE; RATES; ED01 AB In a typical tumorigenicity study, most tumors are not observable in live animals and only a single (terminal) sacrifice is performed. This paper proposes a nonparametric, survival-adjusted analysis for these data that focuses on tumor incidence and yet does not require data on cause of death or assumptions about the tumor's lethality. The tumor onset/death process is most naturally characterized in terms of the tumor incidence rate and the death rates for tumor-free and tumor-bearing animals. The proposed approach, however, reparameterizes the problem in terms of the incidence rate, the death rate for tumor-free animals, and the difference between the death rates for tumor-free and tumor-bearing animals (i.e., the risk difference). The advantage of this alternative formulation is that a full likelihood analysis is possible with as few as one sacrifice time if the risk difference is assumed to be constant with respect to time. Data from the large ED01 study suggest that reasonable results can be obtained under the assumption of constant risk differences. RP DINSE, GE (reprint author), NIEHS,DIV BIOMETRY & RISK ASSESSMENT,B3-02,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 35 TC 25 Z9 25 U1 0 U2 0 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1991 VL 47 IS 2 BP 681 EP 700 DI 10.2307/2532155 PG 20 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA FV774 UT WOS:A1991FV77400025 PM 1912267 ER PT J AU LI, ZH GELLER, NL AF LI, ZH GELLER, NL TI ON THE CHOICE OF TIMES FOR DATA-ANALYSIS IN GROUP SEQUENTIAL CLINICAL-TRIALS SO BIOMETRICS LA English DT Note DE CLINICAL TRIAL DESIGN; INTERIM ANALYSIS; REPEATED SIGNIFICANCE TESTING; USE FUNCTION FOR GROUP SEQUENTIAL TRIALS ID INTERIM ANALYSES; DESIGN; TESTS AB Planned interim analysis of randomized clinical trials has been implemented for over a decade. While the initial proposal advocated analyzing after equal numbers of patients were evaluated, a later modification by Lan and DeMets (1983, Biometrika 70, 659-663) allowed for more flexible boundaries. Rather than fixing the times of analysis at equal numbers of patients, they fixed the rate at which overall alpha was used up according to a use function alpha*(t) on t in [0, 1] with alpha*(0) = 0 and alpha*(1) = alpha. Here we consider how flexible Lan and DeMets' procedure is. We show that the choice of alpha*(t) for a particular trial affects the permissible analysis times if other desirable properties of the sequence of nominal significance levels are to hold. To overcome the difficulties posed by patterns of late analysis, piecewise linear convex use functions are proposed. C1 NHLBI,BIOSTAT RES BRANCH,FED BLDG,ROOM 2A11,7550 WISCONSIN AVE,BETHESDA,MD 20892. MEM SLOAN KETTERING CANC CTR,DIV BIOSTAT,NEW YORK,NY 10021. FU NCI NIH HHS [R01-CA43074] NR 9 TC 7 Z9 7 U1 0 U2 0 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1991 VL 47 IS 2 BP 745 EP 750 DI 10.2307/2532161 PG 6 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA FV774 UT WOS:A1991FV77400031 PM 1912268 ER PT J AU FOLLMANN, DA AF FOLLMANN, DA TI THE EFFECT OF SCREENING ON SOME PRETEST POSTTEST TEST VARIANCES SO BIOMETRICS LA English DT Article DE ANALYSIS OF COVARIANCE; CLINICAL TRIAL; RANGE RESTRICTION; SAMPLE SIZE; T-TEST AB The clinical trial design in which the endpoint is measured both at baseline and at the end of the study is used in a variety of situations. For two-group designs, tests such as the t test or analysis of covariance are commonly used to evaluate treatment efficacy. Often such pretest-posttest trials restrict participation to subjects with a baseline measurement of the endpoint in a certain range. A range may define a disease, or it may be thought that subjects with extreme measurements are more responsive to treatment. This paper examines the effect of screening on the analysis of covariance and t-test variances relative to the population (i.e., unscreened) variances. Bivariate normal and bivariate gamma distributions are assumed for the (pretest, posttest) measurements. Because the sample size required to detect a specified difference between treatment and control is proportional to the variance, the results have direct application to setting sample size. RP FOLLMANN, DA (reprint author), NHLBI,BIOSTAT RES BRANCH,7550 WISCONSIN AVE,ROOM 2A11,BETHESDA,MD 20892, USA. NR 9 TC 10 Z9 10 U1 0 U2 0 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1991 VL 47 IS 2 BP 763 EP 771 DI 10.2307/2532164 PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA FV774 UT WOS:A1991FV77400034 PM 1912270 ER PT J AU SEIGEL, DG PODGOR, MJ AF SEIGEL, DG PODGOR, MJ TI COMPLIANCE, BIAS, AND POWER IN CLINICAL-TRIALS SO BIOMETRICS LA English DT Letter RP SEIGEL, DG (reprint author), NEI,BIOMETRY & EPIDEMIOL PROGRAM,BETHESDA,MD 20892, USA. NR 2 TC 3 Z9 3 U1 1 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1991 VL 47 IS 2 BP 777 EP 778 PG 2 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA FV774 UT WOS:A1991FV77400037 PM 1912272 ER PT J AU GRAUBARD, BI GAIL, MH FEARS, TR AF GRAUBARD, BI GAIL, MH FEARS, TR TI CASE-CONTROL STUDIES WITH CLUSTER SAMPLING SO BIOMETRICS LA English DT Letter RP GRAUBARD, BI (reprint author), NCI,EXECUT PLAZA N,SUITE 344,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1991 VL 47 IS 2 BP 779 EP 780 PG 2 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA FV774 UT WOS:A1991FV77400039 PM 1912273 ER PT J AU LAUTENBERGER, JA AF LAUTENBERGER, JA TI A COMPUTER-PROGRAM TO ASSIST IN THE PREPARATION OF OLIGONUCLEOTIDE SOLUTIONS SO BIOTECHNIQUES LA English DT Article RP LAUTENBERGER, JA (reprint author), NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702, USA. NR 4 TC 3 Z9 3 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JUN PY 1991 VL 10 IS 6 BP 778 EP 780 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FQ809 UT WOS:A1991FQ80900019 PM 1878214 ER PT J AU ROSENFELD, SJ YOUNG, NS AF ROSENFELD, SJ YOUNG, NS TI VIRUSES AND BONE-MARROW FAILURE SO BLOOD REVIEWS LA English DT Review ID NON-B-HEPATITIS; HUMAN-IMMUNODEFICIENCY-VIRUS; EPSTEIN-BARR VIRUS; B19 PARVOVIRUS INFECTION; SICKLE-CELL-ANEMIA; NON-A-HEPATITIS; APLASTIC-ANEMIA; CYTOMEGALO-VIRUS; C VIRUS; VIRAL-HEPATITIS AB Many agents are associated with bone marrow failure, including toxins, inherited metabolic defects, ionizing radiation, and viral infection. In most cases, the etiologic agent is unknown. Many of these unclassified cases have symptomatic, immunologic, or epidemiologic similarities to viral infections. Viruses from different taxonomic families have been implicated in bone marrow failure syndromes, and they appear to cause hematosuppression by a variety of mechanisms. Some of the viruses involved in relatively well characterized suppressive interactions will be reviewed, including parvovirus B19, dengue, hepatitis viruses, Epstein-Barr virus, cytomegalovirus and the human immunodeficiency virus. RP ROSENFELD, SJ (reprint author), NHLBI,CLIN HEMATOL BRANCH,CELL BIOL SECT,10-7C103,BETHESDA,MD 20892, USA. NR 79 TC 42 Z9 42 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0268-960X J9 BLOOD REV JI Blood Rev. PD JUN PY 1991 VL 5 IS 2 BP 71 EP 77 DI 10.1016/0268-960X(91)90037-D PG 7 WC Hematology SC Hematology GA FT209 UT WOS:A1991FT20900001 PM 1655129 ER PT J AU ROBBINS, JH BRUMBACK, RA MENDIONES, M BARRETT, SF CARL, JR CHO, SC DENCKLA, MB GANGES, MB GERBER, LH GUTHRIE, RA MEER, J MOSHELL, AN POLINSKY, RJ RAVIN, PD SONIES, BC TARONE, RE AF ROBBINS, JH BRUMBACK, RA MENDIONES, M BARRETT, SF CARL, JR CHO, SC DENCKLA, MB GANGES, MB GERBER, LH GUTHRIE, RA MEER, J MOSHELL, AN POLINSKY, RJ RAVIN, PD SONIES, BC TARONE, RE TI NEUROLOGICAL DISEASE IN XERODERMA-PIGMENTOSUM - DOCUMENTATION OF A LATE ONSET TYPE OF THE JUVENILE ONSET FORM SO BRAIN LA English DT Article ID DNA-REPAIR CHARACTERISTICS; SANCTIS-CACCHIONE SYNDROME; COMPLEMENTATION GROUP-G; GROUP-F; SENSORINEURAL DEAFNESS; GENETIC-HETEROGENEITY; ULTRAVIOLET-LIGHT; CLINICAL SYMPTOMS; SKIN CANCERS; GROUP-C AB Xeroderma pigmentosum (XP) is an autosomal recessive, neurocutaneous disorder characterized by sunlight-induced skin cancers and defective DNA repair. Many XP children develop a primary neuronal degeneration. We describe 2 unusual XP patients who had a delayed onset of XP neurological disease. Somatic cell genetic studies indicated that they have the same defective DNA repair gene and are both in XP complementation group A. These 2 patients, together with a group A patient previously reported from London, establish as a distinct clinical entity the late onset type of the juvenile onset form of XP neurological disease. The functional capacity of these patients' cultured fibroblast strains to survive after treatment with ultraviolet radiation indicates that their DNA repair defect is less severe than that of typical group A patients who have a more severe neurodegeneration with an earlier symptomatic onset. The premature death of nerve cells in XP patients (which is presumably due to their inherited defects in DNA repair mechanisms) suggests that normal repair of damaged DNA in neurons is required to maintain integrity of the human nervous system. C1 NEI,SENSORIMOTOR RES LAB,BETHESDA,MD 20892. NINCDS,CLIN NEUROSCI PROGRAM,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT REHABIL MED,BETHESDA,MD 20892. UNIV OKLAHOMA,COLL MED,DEPT PATHOL NEUROPATHOL,OKLAHOMA CITY,OK 73104. VET AFFAIRS MED CTR,OKLAHOMA CITY,OK. UNIV KANSAS,SCH MED,DEPT INTERNAL MED,WICHITA,KS. NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. UNIV KANSAS,SCH MED,DEPT PEDIAT,WICHITA,KS. RP ROBBINS, JH (reprint author), NCI,DEPT DERMATOL,BLDG 10,ROOM 12N238,BETHESDA,MD 20892, USA. RI Brumback, Roger/A-2404-2008 NR 87 TC 73 Z9 74 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0006-8950 J9 BRAIN JI Brain PD JUN PY 1991 VL 114 BP 1335 EP 1361 DI 10.1093/brain/114.3.1335 PN 3 PG 27 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA GQ807 UT WOS:A1991GQ80700013 PM 2065254 ER PT J AU MANDERINO, GL LEICHT, JC MULSHINE, JL GOOCH, GT AF MANDERINO, GL LEICHT, JC MULSHINE, JL GOOCH, GT TI CROSS VALIDATION OF CLUSTER-ANALYSIS USING IMMUNOSTAINED MULTI-TISSUE TUMOR BLOCK SLIDES SO BRITISH JOURNAL OF CANCER LA English DT Article; Proceedings Paper CT 2ND INTERNATIONAL WORKSHOP ON SMALL CELL LUNG CANCER ANTIGENS CY APR, 1990 CL ROYAL SOC MED, LONDON, ENGLAND SP UK COORDINATING COMM CANC RES, ABBOTT LABS, CENTOCOR, DAKO LABS, BOEHRINGER MANNHEIM HO ROYAL SOC MED ID MUCIN-TYPE GLYCOPROTEIN; MAB A-80; EXPRESSION; CANCER AB We assayed the panel of SCLC MAbs using multi-tissue tumour block (MTTB) slides obtained from Dr Hector Battifora (City of Hope Hospital, Duarte CA). MTTB slides contain up to 100 different formalin-fixed tumour tissue specimens and can be immunostained with as little as 50-mu-l of antibody solution. In this study, the MAbs in the SCLC panel were used to stain slides from a MTTB comprised of eight normal, ten SCLC, ten squamous cell, ten adenocarcinoma and five undifferentiated lung cancer tissues. Many MAbs in the SCLC panel failed to immunostain the lung MTTB whereas many others showed significant immunoreactivity. Of those MAbs that stained SCLC tissue, none was found to be specific; these MAbs also stained NSCLC tissues or normal lung tissues. Some MAbs in the panel immunostained SCLC and NSCLC tissues, but were also reactive to normal lung tissue as well as other normal tissue specimens. A major advantage of immunostaining MTTBs with a panel of MAbs is that we were able to compare the immunoreactivity of the MAbs on a total of 128 different tissues requiring only 100-mu-l of antibody solution using only two MTTB slides per MAb. Although this study was preliminary and certain technical problems in assembling the MTTB as well as optimising the immunostaining procedure for handling 98 or more MAbs simultaneously remain, the MTTB technique remains promising. C1 USN,MED CTR,NCI,MED ONCOL BRANCH,BETHESDA,MD 20814. RP MANDERINO, GL (reprint author), ABBOTT LABS,DEPT CANC RES & IMMUNOL,D-90C,N CHICAGO,IL 60064, USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUN PY 1991 VL 63 SU 14 BP 60 EP 63 PG 4 WC Oncology SC Oncology GA FP061 UT WOS:A1991FP06100017 ER PT J AU ANDERSON, LM JONES, AB RICE, JM AF ANDERSON, LM JONES, AB RICE, JM TI PERINATAL CARCINOGENESIS - CURRENT DIRECTIONS SO BRITISH JOURNAL OF CANCER LA English DT Editorial Material RP ANDERSON, LM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,PERINATAL CARCINOGENESIS SECT,FREDERICK,MD 21702, USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUN PY 1991 VL 63 IS 6 BP 1025 EP 1028 DI 10.1038/bjc.1991.224 PG 4 WC Oncology SC Oncology GA FU823 UT WOS:A1991FU82300039 PM 2069840 ER PT J AU SCHWAN, TG KARSTENS, RH SCHRUMPF, ME SIMPSON, WJ AF SCHWAN, TG KARSTENS, RH SCHRUMPF, ME SIMPSON, WJ TI CHANGES IN ANTIGENIC REACTIVITY OF BORRELIA-BURGDORFERI, THE LYME-DISEASE SPIROCHETE, DURING PERSISTENT INFECTION IN MICE SO CANADIAN JOURNAL OF MICROBIOLOGY LA English DT Article DE BORRELIA-BURGDORFERI; LYME DISEASE; ANTIGENIC CHANGES ID INVITRO CULTIVATION; PEROMYSCUS-LEUCOPUS; SURFACE PROTEIN; STRAINS AB Adult laboratory mice, Mus musculus, were shown to be suitable experimental animals for studying infectivity, persistent infection, and in vivo antigenic changes of Borrelia burgdorferi. Sixteen mice were inoculated intraperitoneally with a low-passage culture of an uncloned strain of B. burgdorferi and 16 months later spirochetes were reisolated from the urinary bladder of 15 (94%) of the mice. Spirochetes recovered from the urinary bladder of one persistently infected mouse were tested for infectivity and found to be infectious when passaged into four laboratory mice. Western blot analysis of immune serum from each of the persistently infected mice demonstrated that spirochetes used to infect the mice reacted differently when compared with the spirochetes subsequently reisolated from the mice, demonstrating for the first time that changes in antigenic reactivity had occurred in the spirochete populations during persistent infection. RP SCHWAN, TG (reprint author), NIAID,ARTHROPOD BORNE DIS SECT,VECTORS & PATHOGENS LAB,ROCKY MT LABS,HAMILTON,MT 59840, USA. NR 18 TC 37 Z9 37 U1 1 U2 1 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0008-4166 J9 CAN J MICROBIOL JI Can. J. Microbiol. PD JUN PY 1991 VL 37 IS 6 BP 450 EP 454 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology GA FX183 UT WOS:A1991FX18300008 PM 1913349 ER PT J AU SAFTLAS, AF HOOVER, RN BRINTON, LA SZKLO, M OLSON, DR SALANE, M WOLFE, JN AF SAFTLAS, AF HOOVER, RN BRINTON, LA SZKLO, M OLSON, DR SALANE, M WOLFE, JN TI MAMMOGRAPHIC DENSITIES AND RISK OF BREAST-CANCER SO CANCER LA English DT Article ID PARENCHYMAL PATTERNS; FEATURES; TISSUE; HEIGHT; WEIGHT AB To determine the relation of mammographic densities to subsequent breast cancer risk, a case-control study was undertaken using prediagnostic mammograms of screening program participants. Mammograms of cases (n = 266) and controls (n = 301) were blindly assessed for mammographic densities, which were measured by planimetry. The odds of breast cancer increased steadily with increasing breast density (test for trend, P < 0.0001). Breast cancer odds was 1.7 for densities between 5% and 24.9%, 2.5 for 25% through 44.9%, 3.8 for 45% through 64%, and 4.3 for densities of 65% and greater (referent = < 5% densities). Odds ratios also increased with increasing densities among women with the P2 and DY mammographic patterns. These findings suggest that the percentage of mammographic densities in the breast can predict breast cancer risk more accurately than a qualitative assessment of mammographic patterns. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21218. HUTZEL HOSP,DEPT RADIOL,DETROIT,MI 48201. CTR DIS CONTROL,CTR CHRON DIS PREVENT & HLTH PROMOT,DIV DIABET CONTROL,ATLANTA,GA 30333. NCI,DIV CANC ETIOL,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP SAFTLAS, AF (reprint author), CTR DIS CONTROL,CTR CHRON DIS PREVENT & HLTH PROMOT,DIV REPROD HLTH,ATLANTA,GA 30333, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU NCI NIH HHS [T 32 CA09314-07] NR 20 TC 180 Z9 181 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 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 1991 VL 67 IS 11 BP 2833 EP 2838 DI 10.1002/1097-0142(19910601)67:11<2833::AID-CNCR2820671121>3.0.CO;2-U PG 6 WC Oncology SC Oncology GA FM140 UT WOS:A1991FM14000020 PM 2025849 ER PT J AU CRAGG, GM SNADER, KM AF CRAGG, GM SNADER, KM TI TAXOL - THE SUPPLY ISSUE SO CANCER CELLS-A MONTHLY REVIEW LA English DT Editorial Material ID AGENT RP CRAGG, GM (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,NAT PROD BRANCH,BETHESDA,MD 20892, USA. NR 6 TC 45 Z9 45 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1042-2196 J9 CANCER CELL-MON REV PD JUN PY 1991 VL 3 IS 6 BP 233 EP 235 PG 3 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA FU015 UT WOS:A1991FU01500004 PM 1680362 ER PT J AU CASSIDY, J MACFARLANE, DK AF CASSIDY, J MACFARLANE, DK TI THE ROLE OF THE NURSE IN CLINICAL CANCER-RESEARCH SO CANCER NURSING LA English DT Article DE DATA MANAGEMENT; CLINICAL TRIALS; RESEARCH NURSE; CLINICAL RESEARCH AB Although advances have been made in the treatment of a number of cancers, no standard effective treatment exists for many forms of the disease. To answer remaining questions about cancer therapy, patients are encouraged to enter clinical trials that test new therapies or combinations of therapies. These trials take place not only in cancer centers and large university hospitals, but also in community hospitals and private offices throughout the country. The nurse can be an active participant in these trials as both the patient advocate and the liaison between the patient and the physician or the nurse researcher responsible for conducting the clinical investigation. Each protocol contains specific guidelines that include eligibility requirements, detailed treatment regimens, patient evaluations, and data collection schedules. The regulatory issues or Institutional Review Board (IRB) approval, informed consent, toxicity reporting, and maintenance of accurate records for investigational drug accountability are also part of the research process. A nurse who is well informed on these issues is an asset to the successful completion of any clinical study. RP CASSIDY, J (reprint author), NCI,CLIN ONCOL PROGRAM,BLDG 10,ROOM 12N-214,BETHESDA,MD 20892, USA. NR 0 TC 9 Z9 10 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD JUN PY 1991 VL 14 IS 3 BP 124 EP 131 DI 10.1097/00002820-199114030-00002 PG 8 WC Oncology; Nursing SC Oncology; Nursing GA FM139 UT WOS:A1991FM13900002 PM 2059955 ER PT J AU PAI, LH GALLO, MG FITZGERALD, DJ PASTAN, I AF PAI, LH GALLO, MG FITZGERALD, DJ PASTAN, I TI ANTITUMOR-ACTIVITY OF A TRANSFORMING GROWTH-FACTOR ALPHA-PSEUDOMONAS EXOTOXIN FUSION PROTEIN (TGF-ALPHA-PE40) SO CANCER RESEARCH LA English DT Article ID NUDE-MOUSE MODEL; RICIN-A-CHAIN; FACTOR RECEPTOR; ANTIBODY; MICE; IMMUNOTOXINS; CELLS; CANCER; TUMORS AB TGF-alpha-PE40 is a chimeric protein composed of transforming growth factor-alpha (TGF-alpha) linked to a modified Pseudomonas toxin from which the cell recognition domain has been deleted (PE40). TGF-alpha-PE40 has been shown to have cytotoxic effects on human cancer cell lines that express the epidermal growth factor (EGF) receptor on their surface, and when given i.p., it prolongs the survival of nude mice bearing i.p. tumors. Because several normal tissues, including liver, express EGF receptors on their surfaces, it has not been clear that this agent can be used systemically to treat EGF receptor-bearing tumors. In this study, we have delivered TGF-alpha-PE40 for 7 days by continuous infusion through a miniosmotic pump placed in the peritoneal cavity of nude immunodeficient mice. Two different human cancer cell lines that express EGF receptors on their surface were implanted s.c. One was A431, an epidermoid carcinoma; the other was DU-145, a prostate carcinoma. By using this mode of continuous i.p. delivery, we were able to achieve a constant serum level of TGF-alpha-PE40 that was nontoxic to the mice and yet delayed the growth of both tumors implanted s.c. and caused partial regression of one. We conclude that it is possible to deliver TGF-alpha-PE40 systemically and achieve a therapeutic serum level in mice without major toxicity. Although side effects may be expected, this study establishes that there is a therapeutic window for this agent in the therapy of cancers with high numbers of EGF receptors. C1 NCI,DIV CANC BIOL DIAG & CENTERS,MOLEC BIOL LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 27 TC 72 Z9 72 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1991 VL 51 IS 11 BP 2808 EP 2812 PG 5 WC Oncology SC Oncology GA FM978 UT WOS:A1991FM97800009 PM 2032221 ER PT J AU SIEGALL, CB KREITMAN, RJ FITZGERALD, DJ PASTAN, I AF SIEGALL, CB KREITMAN, RJ FITZGERALD, DJ PASTAN, I TI ANTITUMOR EFFECTS OF INTERLEUKIN-6-PSEUDOMONAS EXOTOXIN CHIMERIC MOLECULES AGAINST THE HUMAN HEPATOCELLULAR-CARCINOMA, PLC/PRF/5 IN MICE SO CANCER RESEARCH LA English DT Article ID PSEUDOMONAS EXOTOXIN; DOMAIN-II; EXPRESSION; RECEPTOR; CELLS; GENE; GENERATION; TOXICITY; LEUKEMIA; LIVER AB IL6-PE40 and IL6-PE66(4Glu) are chimeric molecules composed of interleukin 6 (IL6) fused to a truncated form (PE40) or a full-length mutated form (PE66(4Glu)) of Pseudomonas exotoxin. Both forms of IL6-Pseudomonas exotoxin are cytotoxic to IL6 receptor-bearing tumor cell types in culture. In this report, we show that both IL6-PE40 and IL6-PE66(4Glu) have antitumor activity against the hepatocellular carcinoma PLC/PRF/5 implanted s.c. in nude mice. The PLC/PRF/5 tumor contains about 2300 IL6 receptors per cell. IL6-PE66(4Glu) showed improved therapeutic efficacy when released continuously for 7 days by an osmotic pump planted i.p. than when administered by multiple daily i.p. injections. Both forms of IL6 toxin exhibited a schedule-dependent antitumor effect. These results demonstrate that IL6-Pseudomonas exotoxin can suppress the growth of cancer which overexpresses cell surface IL6 receptors. C1 NCI,DIV CANC BIOL DIAG & CENTERS,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 29 TC 41 Z9 41 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 JUN 1 PY 1991 VL 51 IS 11 BP 2831 EP 2836 PG 6 WC Oncology SC Oncology GA FM978 UT WOS:A1991FM97800013 PM 1851660 ER PT J AU SHOEMAKER, RH DYKES, DJ PLOWMAN, J HARRISON, SD GRISWOLD, DP ABBOTT, BJ MAYO, JG FODSTAD, O BOYD, MR AF SHOEMAKER, RH DYKES, DJ PLOWMAN, J HARRISON, SD GRISWOLD, DP ABBOTT, BJ MAYO, JG FODSTAD, O BOYD, MR TI PRACTICAL SPONTANEOUS METASTASIS MODEL FOR INVIVO THERAPEUTIC STUDIES USING A HUMAN-MELANOMA SO CANCER RESEARCH LA English DT Article ID ATHYMIC NUDE-MICE; HUMAN CANCER METASTASIS; CARCINOMA CELL-LINE; TUMOR-CELLS; LUNG; MOUSE; ESTABLISHMENT; BEHAVIOR; BIOLOGY; VARIANT AB In vivo studies aimed at therapy of spontaneous human tumor metastases have been hampered by the lack of practical experimental models. The LOX amelanotic melanoma model described here represents a transplantation model which rapidly and reproducibly results in spontaneous pulmonary metastasis following s.c. inoculation into athymic mice. Pulmonary lesions can be detected using a simple bioassay procedure which is useful for estimation of metastatic cell killing. Using this model we demonstrate that systemic therapy with cyclophosphamide or dacarbazine can produce metastatic cell killing consistent with complete eradication of established pulmonary metastases. This model may also prove useful for future experimental therapeutic studies aimed at prevention of metastases by manipulating tumor staging interval and treatment schedule. C1 SO RES INST,BIRMINGHAM,AL 35255. NORWEGIAN RADIUM HOSP,INST CANC RES,OSLO 3,NORWAY. RP SHOEMAKER, RH (reprint author), NCI,THERAPEUT PROGRAM,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CM-67911, N01-CM-47581] NR 34 TC 17 Z9 17 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1991 VL 51 IS 11 BP 2837 EP 2841 PG 5 WC Oncology SC Oncology GA FM978 UT WOS:A1991FM97800014 PM 2032224 ER PT J AU TUCKER, MA JONES, PHM BOICE, JD ROBISON, LL STONE, BJ STOVALL, M JENKIN, RDT LUBIN, JH BAUM, ES SIEGEL, SE MEADOWS, AT HOOVER, RN FRAUMENI, JF AF TUCKER, MA JONES, PHM BOICE, JD ROBISON, LL STONE, BJ STOVALL, M JENKIN, RDT LUBIN, JH BAUM, ES SIEGEL, SE MEADOWS, AT HOOVER, RN FRAUMENI, JF TI THERAPEUTIC RADIATION AT A YOUNG AGE IS LINKED TO SECONDARY THYROID-CANCER SO CANCER RESEARCH LA English DT Article ID CHILDHOOD IRRADIATION; HODGKINS-DISEASE; RADIOTHERAPY; TUMORS; MORTALITY; SURVIVORS; NEOPLASMS; RISK AB We estimated the risk of thyroid cancer among 9170 patients who had survived 2 or more years after the diagnosis of a cancer in childhood. As compared with the general populations, patients had a 53-fold increased risk (95% confidence interval, 34-80). Risk increased significantly with time since treatment for the initial cancer (P = 0.03). Detailed treatment data were obtained for 23 cases and 89 matched controls from the childhood cancer cohort. Sixty-eight % of the thyroid cancers arose within the field of radiation. Radiation doses to the thyroid of > 200 cGy were associated with a 13-fold increased risk (95% confidence interval, 1.7-104). The risk of thyroid cancer rose with increasing dose (P < 0.001), but this was derived almost entirely from the increase from < 200 to > 200 cGy. The risk of thyroid cancer did not decrease, however, at radiation doses as high as 6000 cGy. C1 NCI, DIV CANC ETIOL, EPIDEMIOL & BIOSTAT PROGRAM, BETHESDA, MD 20892 USA. ROYAL MANCHESTER CHILDRENS HOSP, PENDLEBURY M27 1HA, ENGLAND. UNIV MINNESOTA HOSP, MINNEAPOLIS, MN 55404 USA. UNIV TEXAS, MD ANDERSON CANC CTR, HOUSTON, TX 77030 USA. SUNNYBROOK MED CTR, TORONTO M4N 3M5, ONTARIO, CANADA. CHILDRENS MEM HOSP, CHICAGO, IL 60614 USA. CHILDRENS HOSP LOS ANGELES, LOS ANGELES, CA 90027 USA. CHILDRENS HOSP PHILADELPHIA, PHILADELPHIA, PA 19104 USA. RI Tucker, Margaret/B-4297-2015 FU NCI NIH HHS [N01CP-91049] NR 29 TC 220 Z9 224 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1991 VL 51 IS 11 BP 2885 EP 2888 PG 4 WC Oncology SC Oncology GA FM978 UT WOS:A1991FM97800022 PM 1851664 ER PT J AU SCHLOM, J SILER, K MILENIC, DE EGGENSPERGER, D COLCHER, D MILLER, LS HOUCHENS, D CHENG, R KAPLAN, D GOECKELER, W AF SCHLOM, J SILER, K MILENIC, DE EGGENSPERGER, D COLCHER, D MILLER, LS HOUCHENS, D CHENG, R KAPLAN, D GOECKELER, W TI MONOCLONAL ANTIBODY-BASED THERAPY OF A HUMAN TUMOR XENOGRAFT WITH A LUTETIUM-177-LABELED IMMUNOCONJUGATE SO CANCER RESEARCH LA English DT Article ID CARCINOMA XENOGRAFTS; COLON CANCER; B72.3; ANTIGEN; RADIOIMMUNOTHERAPY; CELLS; GENERATION; PROTEINS; BINDING; Y-90 AB Lutetium-177(Lu-177) is a member of the family of elements known as lanthanides or rare earths. Monoclonal antibody (MAb) CC49, a murine IgG1, which is reactive with the tumor-associated antigen, TAG-72, has been shown previously to react with a wide range of human carcinomas; CC49 reacts to a different epitope on the TAG-72 molecule than MAb B72.3 and has a higher binding affinity. We report here the first use of a Lu-177-labeled immunoconjugate, Lu-177-CC49, in experimental therapy model for human carcinoma. Lu-177-CC49 was shown to delay the growth of established LS-174T human colon carcinomas in athymic mice at a single dose of 50-mu-Ci. Overt toxicity was observed with the administration of approximately 500-mu-Ci of Lu-177-CC49 in which 5 of 9 mice died of apparent marrow toxicity. A single administration of 200 or 350-mu-Ci of Lu-177-CC49, however, was shown to eliminate established tumors through the 77-day observation period after MAb administration. Dose fractionation experiments revealed that at least 750-mu-Ci of Lu-177-CC49 (250-mu-Ci/week for 3 consecutive weeks) was well tolerated in that 9 of 10 mice survived. Moreover, this dose schedule was able to eliminate the growth of relatively large (300 mm3) human colon tumor xenografts in 90% of the animals treated. Single-dose and dose fractionation studies were also carried out with an isotype-matched control MAb, Lu-177-MOPC-21. In all dose schedules, a large differential was seen between the therapeutic effects of the Lu-177-CC49 versus that of the Lu-177-control MAb. The merits and limitations of the use of Lu-177-labeled immunoconjugates (in particular, Lu-177-CC49) are discussed in terms of potential novel therapeutics for human carcinoma. C1 BATTELLE MEM INST,COLUMBUS,OH 43201. DOW CHEM CO USA,MIDLAND,MI 48674. RP SCHLOM, J (reprint author), NCI,TUMOR IMMUNOL & BIOL LAB,BLDG 10,ROOM 8B07,BETHESDA,MD 20892, USA. NR 37 TC 110 Z9 110 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1991 VL 51 IS 11 BP 2889 EP 2896 PG 8 WC Oncology SC Oncology GA FM978 UT WOS:A1991FM97800023 PM 1851665 ER PT J AU PURI, RK OGATA, M LELAND, P FELDMAN, GM FITZGERALD, D PASTAN, I AF PURI, RK OGATA, M LELAND, P FELDMAN, GM FITZGERALD, D PASTAN, I TI EXPRESSION OF HIGH-AFFINITY INTERLEUKIN-4 RECEPTORS ON MURINE SARCOMA-CELLS AND RECEPTOR-MEDIATED CYTOTOXICITY OF TUMOR-CELLS TO CHIMERIC PROTEIN BETWEEN INTERLEUKIN-4 AND PSEUDOMONAS EXOTOXIN SO CANCER RESEARCH LA English DT Article ID FACTOR-I; LYMPHOID-CELLS; IL-4 RECEPTOR; UP-REGULATION; LYMPHOCYTES; ANTIBODIES; BINDING; INVITRO AB The presence of interleukin 4 receptor (IL-4R) on methylcholanthrene (MCA-106, MCA-102, and MC-38)- and viral DNA (G-2TS and 14-2TS)-induced murine sarcoma cells was demonstrated. MCA-106 tumor cells express about 500 to 1348 (median, 800) interleukin 4 (IL-4) binding sites/cell with a dissociation constant (K(d)) of 115 +/- 26 pM (mean +/- SD, n = 4). By Northern blot analysis, tumor cells exhibited a single mRNA species of 3.9 kilobases. Other murine sarcoma (MCA-102), colon adenocarcinoma (MC-38), G-2TS, and 14-2TS tumor cells express low numbers of IL-4R. By immunoperoxidase staining, 81 to 92% of the cells from fresh MCA-106 tumors were positive for IL-4 receptors, while only 7 to 10% of tumor-infiltrating cells were Thy 1.2 and < 1% Mac-1 positive. Using a chimeric protein composed of IL-4 and Pseudomonas exotoxin (IL-4-PE40), we observed that IL-4-PE40 was cytotoxic (determined by inhibition of protein synthesis by [H-3]leucine uptake) to MCA-106 tumor cells in a dose-dependent manner. A nonchimeric protein (PE40) that cannot bind to the IL-4R did not inhibit protein synthesis in tumor cells. A chimeric mutant protein (IL4-PE40 asp553) that can bind to IL-4 receptors but does not have the capability to inhibit protein synthesis was not cytotoxic to tumor cells. These studies strongly suggest that IL-4R on murine MCA-106 sarcoma cells is internalized when occupied by IL-4-PE40. Furthermore, a neutralizing antibody (11B11) to IL-4 completely abolished the protein synthesis-inhibitory activity of IL-4-PE40. G-2TS tumor cells which expressed low numbers of IL-4 receptors were not vulnerable to cytotoxicity by IL-4-PE40. Taken together, these data suggest that IL-4 receptor may be a target for IL-4-toxin therapy. C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. RP PURI, RK (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,CELLULAR IMMUNOL LAB,BLDG 29A,ROOM 2B20,BETHESDA,MD 20892, USA. NR 22 TC 54 Z9 55 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 JUN 1 PY 1991 VL 51 IS 11 BP 3011 EP 3017 PG 7 WC Oncology SC Oncology GA FM978 UT WOS:A1991FM97800042 PM 2032239 ER PT J AU PANELLA, TJ LIU, YH HUANG, AT TENG, CT AF PANELLA, TJ LIU, YH HUANG, AT TENG, CT TI POLYMORPHISM AND ALTERED METHYLATION OF THE LACTOFERRIN GENE IN NORMAL LEUKOCYTES, LEUKEMIC-CELLS, AND BREAST-CANCER SO CANCER RESEARCH LA English DT Article ID LACTOTRANSFERRIN GENE; NUCLEOTIDE-SEQUENCE; MAMMARY-GLAND; TRANSFERRIN; EXPRESSION; BINDING; FORMS; MYELOPOIESIS; CARCINOMAS; MEMBRANE AB Human lactoferrin has been found to be decreased or absent in most breast cancer and leukemia cells. In order to examine the lactoferrin gene for both structural alterations and the degree of methylation, we isolated a 2117-kilobase complementary DNA from human breast tissue. This complementary DNA was used to probe DNA extracted from normal peripheral blood, leukemia cells from patients, leukemia cell lines, and breast cancer cell lines. Immunocytochemical staining of these cells confirmed the decreased production of lactoferrin in malignancy. MspI restriction enzyme fragment patterns demonstrated genetic polymorphism which occurred in DNA from both normal and malignant cells. Polymorphism was also noted with XbaI. In this case, there were two fragment patterns that were only found in DNA from malignant cells. The degree of DNA methylation was also evaluated. The methylation pattern of DNA extracted from malignant cells was highly variable and generally less methylated than DNA extracted from normal WBCs. It is possible that the decrease in lactoferrin associated with cancer is multifactorial and includes gene structural changes as well as altered regulation. Further study is needed to determine whether the changes found in this study are the result of the malignancy or contribute to its onset or maintenance. C1 NIEHS,REPROD & DEV TOXICOL LAB,BOX 12233,MD 1301,RES TRIANGLE PK,NC 27709. DEPT MED,DIV HEMATOL ONCOL,DURHAM,NC 27710. NR 38 TC 45 Z9 46 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1991 VL 51 IS 11 BP 3037 EP 3043 PG 7 WC Oncology SC Oncology GA FM978 UT WOS:A1991FM97800046 PM 1674448 ER PT J AU WINN, DM BLOT, WJ MCLAUGHLIN, JK AUSTIN, DF GREENBERG, RS PRESTONMARTIN, S SCHOENBERG, JB FRAUMENI, JF AF WINN, DM BLOT, WJ MCLAUGHLIN, JK AUSTIN, DF GREENBERG, RS PRESTONMARTIN, S SCHOENBERG, JB FRAUMENI, JF TI MOUTHWASH USE AND ORAL CONDITIONS IN THE RISK OF ORAL AND PHARYNGEAL CANCER SO CANCER RESEARCH LA English DT Article ID SMOKING; INFECTION; ALCOHOL AB Interviews with 866 patients with cancer of the oral cavity and pharynx and 1249 controls of similar age and sex from the general population in four areas of the United States revealed increased risks associated with the regular use of mouthwash. Risks of oral cancer were elevated by 40% among male and 60% among female mouthwash users, after adjusting for tobacco and alcohol consumption. Risks among both sexes generally increased in proportion to duration and frequency of mouthwash use. The increased risks were confined to users of mouthwash high in alcohol content, consistent with the elevated risks associated with drinking alcoholic beverages. Except for a higher prevalence of leukoplakia among cases, little relationship was found with oral or dental conditions, although denture wearing was reported more often by patients with cancer of the gums. These findings, together with other studies, provide further incentive for clarifying the association between mouthwash use and oral cancer. C1 NCI,EPN 431,BETHESDA,MD 20892. NATL CTR HLTH STAT,HYATTSVILLE,MD 20782. CALIF DEPT HLTH SERV,EMERYVILLE,CA 94608. EMORY UNIV,ATLANTA,GA 30322. UNIV SO CALIF,LOS ANGELES,CA 90033. NEW JERSEY DEPT HLTH,TRENTON,NJ 08625. NR 25 TC 114 Z9 120 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1991 VL 51 IS 11 BP 3044 EP 3047 PG 4 WC Oncology SC Oncology GA FM978 UT WOS:A1991FM97800047 PM 2032242 ER PT J AU HSING, AW MCLAUGHLIN, JK BLOT, WJ AF HSING, AW MCLAUGHLIN, JK BLOT, WJ TI DIET, TOBACCO USE, AND FATAL PROSTATE-CANCER - RESULTS FROM THE LUTHERAN BROTHERHOOD COHORT STUDY - REPLY SO CANCER RESEARCH LA English DT Letter RP HSING, AW (reprint author), NCI,BETHESDA,MD 20892, USA. NR 4 TC 1 Z9 1 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 JUN 1 PY 1991 VL 51 IS 11 BP 3068 EP 3068 PG 1 WC Oncology SC Oncology GA FM978 UT WOS:A1991FM97800054 ER PT J AU LIPKIN, M NEWMARK, H BOONE, CW KELLOFF, GJ AF LIPKIN, M NEWMARK, H BOONE, CW KELLOFF, GJ TI CALCIUM, VITAMIN-D, AND COLON CANCER SO CANCER RESEARCH LA English DT Editorial Material C1 NCI,CHEMOPREVENT BRANCH,BETHESDA,MD 20852. RP LIPKIN, M (reprint author), MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021, USA. NR 0 TC 27 Z9 27 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1991 VL 51 IS 11 BP 3069 EP 3070 PG 2 WC Oncology SC Oncology GA FM978 UT WOS:A1991FM97800055 PM 2032249 ER PT J AU RAO, CV TOKOMO, K KELLOFF, G REDDY, BS AF RAO, CV TOKOMO, K KELLOFF, G REDDY, BS TI INHIBITION BY DIETARY OLTIPRAZ OF EXPERIMENTAL INTESTINAL CARCINOGENESIS INDUCED BY AZOXYMETHANE IN MALE F344 RATS SO CARCINOGENESIS LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUG; COLON CARCINOGENESIS; 5-(2-PYRAZINYL)-4-METHYL-1,2-DITHIOL-3-THIONE OLTIPRAZ; CANCER; METHYLAZOXYMETHANOL; CHEMOPREVENTION; DITHIOLTHIONES; TUMORIGENESIS; METHYLATION; PROTECTION AB Epidemiological studies suggest that consumption of cruciferous vegetables rich in dithiolethiones is associated with a reduction in the incidence of cancer in man. The effect of two dose levels of dietary oltipraz [5-(2-pyrazinyl)-4-methyl-1, 2-dithiole-3-thione], a substituted dithiolethione, on azoxymethane (AOM)-induced intestinal carcinogenesis and on serum levels was studied in male F344 rats. The maximum tolerated dose (MTD) of oltipraz was determined in male F344 rats and found to be 500 p.p.m. Oltipraz at levels of 200 p.p.m. (40% MTD) and 400 p.p.m. (80% MTD) diet was tested as inhibitor of intestinal carcinogenesis. At 5 weeks of age, animals were fed the modified AIN-76A (control) diet and experimental diets containing oltipraz. At 7 weeks of age, all animals except the vehicle-treated animals were administered s.c. injection of AOM (15 mg/kg body wt/week for 2 weeks). Animals intended for vehicle treatment were administered s.c. with an equal volume of normal saline. Fifty-two weeks later, all animals were killed and colon and small intestinal tumor incidences and multiplicity were compared among the dietary groups. The results indicate that feeding of 200 and 400 p.p.m. of oltipraz significantly inhibited the incidence of adenocarcinomas in colon and small intestine and multiplicity of colon adenomas and small intestinal adenocarcinomas. Animals fed 400 p.p.m. oltipraz showed increased levels of oltipraz in the serum as compared to those fed 200 p.p.m. oltipraz. The results of this study indicate that dietary oltipraz inhibits intestinal carcinogenesis. C1 AMER HLTH FDN,DIV NUTR CARCINOGENESIS,ONE DANA RD,VALHALLA,NY 10595. NCI,CHEMOPREVENT BRANCH,DIV CANC CONTROL & PREVENT,BETHESDA,MD 20892. RI Chinthalapally, Rao/B-3633-2010 FU NCI NIH HHS [N0I-CN-85095-01, CA-17613] NR 33 TC 76 Z9 76 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 1991 VL 12 IS 6 BP 1051 EP 1055 DI 10.1093/carcin/12.6.1051 PG 5 WC Oncology SC Oncology GA FQ426 UT WOS:A1991FQ42600017 PM 2044183 ER PT J AU CANELLA, K PELTONEN, K DIPPLE, A AF CANELLA, K PELTONEN, K DIPPLE, A TI IDENTIFICATION OF (+) AND (-) ANTI-BENZO[A]PYRENE DIHYDRODIOL EPOXIDE NUCLEIC-ACID ADDUCTS BY THE P-32 POSTLABELING ASSAY SO CARCINOGENESIS LA English DT Article ID DNA ADDUCTS; MAMMALIAN-CELLS; METABOLIC ACTIVATION; DIOL-EPOXIDE; BENZO(A)PYRENE; 7,12-DIMETHYLBENZANTHRACENE; CARCINOGENESIS; 1,2-EPOXIDES; ADENINE AB Purine deoxyribonucleoside 3'-phosphates were reacted with the (+)- and (-)-enantiomers of the anti dihydrodiol epoxide of benzo[a]pyrene. Products from cis and trans opening of the epoxide ring were separated by HPLC and they were identified by comparison of their CD spectra with those known for the corresponding nucleoside adducts. Thereafter, the eight known benzo[a]pyrene-purine deoxyribonucleoside-3'-phosphate adducts were postlabeled with [P-32]ATP and T4 kinase and the positions of these individual bisphosphates were mapped by TLC. Though all eight adducts migrated to the same general region of the thin layer plates, the four possible adducts from each enantiomeric dihydrodiol epoxide were resolved. RP CANELLA, K (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHEM CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101] NR 25 TC 45 Z9 45 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 1991 VL 12 IS 6 BP 1109 EP 1114 DI 10.1093/carcin/12.6.1109 PG 6 WC Oncology SC Oncology GA FQ426 UT WOS:A1991FQ42600027 PM 1904321 ER PT J AU WEINBERG, WC MORGAN, DL GEORGE, C YUSPA, SH AF WEINBERG, WC MORGAN, DL GEORGE, C YUSPA, SH TI A COMPARISON OF INTERFOLLICULAR AND HAIR FOLLICLE DERIVED CELLS AS TARGETS FOR THE V-RASHA ONCOGENE IN MOUSE SKIN CARCINOGENESIS SO CARCINOGENESIS LA English DT Note ID MURINE SARCOMA-VIRUSES; ROOT SHEATH-CELLS; CHEMICAL CARCINOGENESIS; MALIGNANT CONVERSION; GAMMA-GLUTAMYLTRANSFERASE; TERMINAL DIFFERENTIATION; EPIDERMAL HYPERPLASIA; ACTIVATED ONCOGENES; TUMOR PROMOTION; MICE AB Methods to isolate and culture intact mouse hair follicles and interfollicular epidermal cells provide a model to test the potential of each to form tumors as a consequence of ras(Ha) gene activation and to determine the risk for progression in the resultant tumors. The v-ras(Ha) oncogene was introduced into intact or dissociated hair follicle cells or interfollicular epidermal cells from newborn mouse skin via a defective retroviral vector. Either immediately after infection or after an additional 6 days of culture, the v-ras(Ha) cells were transferred to nude mice as a skin graft. Both cell populations formed squamous papillomas which were indistinguishable based on morphology and immunocytochemistry. All papillomas expressed epidermal specific markers whether derived from hair follicle or interfollicular cells, and many regressed. After 16 weeks in vivo, 20-30% of the benign skin tumors in all groups converted to malignancy. In addition to papillomas, hair follicle derived populations produced hemangiomas in many animals. None of the groups formed basal cell carcinomas, keratoacanthomas or tumors with characteristics of differentiating hair follicle cells. These studies indicate that ras gene activation can contribute to benign squamous neoplasia originating from several skin-derived cell types. The underlying factors which determine the variable risk for neoplastic progression of skin papillomas after ras gene activation is not simply the origin of the tumor cell from hair follicle or interfollicular epidermis. The activated ras oncogene can also transform skin endothelial cells but does not appear to directly contribute to transformation of the more differentiated cells of the hair follicle. C1 BIOCON INC,ROCKVILLE,MD. RP WEINBERG, WC (reprint author), NCI,DIV CANC ETIOL,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892, USA. RI Weinberg, Wendy/A-8920-2009 NR 49 TC 14 Z9 15 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 1991 VL 12 IS 6 BP 1119 EP 1124 DI 10.1093/carcin/12.6.1119 PG 6 WC Oncology SC Oncology GA FQ426 UT WOS:A1991FQ42600029 PM 2044193 ER PT J AU MUNAUT, C NOEL, A SOBEL, M FOIDART, JM AF MUNAUT, C NOEL, A SOBEL, M FOIDART, JM TI EXPRESSION OF LAMININ BY HUMAN FIBROBLASTS, HT-1080 FIBROSARCOMA CELLS AND MCF-7 BREAST ADENOCARCINOMA CELLS - LACK OF REGULATION BY THE CELL-DENSITY AND EXTRACELLULAR-MATRIX SO CELL BIOLOGY INTERNATIONAL REPORTS LA English DT Article ID BASEMENT-MEMBRANE; SKIN FIBROBLASTS; MESSENGER-RNA; CARCINOMA-CELLS; IV PROCOLLAGEN; COLLAGEN; ATTACHMENT; RECEPTOR; ADHESION; CLONING C1 STATE UNIV LIEGE,BIOL LAB,B-4000 LIEGE,BELGIUM. NIH,PATHOL LAB,BETHESDA,MD 20892. OI Noel, Agnes/0000-0002-7670-6179 NR 37 TC 5 Z9 5 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0309-1651 J9 CELL BIOL INT REP PD JUN PY 1991 VL 15 IS 6 BP 499 EP 509 PG 11 WC Cell Biology SC Cell Biology GA FV201 UT WOS:A1991FV20100007 PM 1742797 ER PT J AU WANG, Y BOGUSKI, M RIGGS, M RODGERS, L WIGLER, M AF WANG, Y BOGUSKI, M RIGGS, M RODGERS, L WIGLER, M TI SAR1, A GENE FROM SCHIZOSACCHAROMYCES POMBE ENCODING A PROTEIN THAT REGULATES RAS1 SO CELL REGULATION LA English DT Article ID GTPASE-ACTIVATING PROTEIN; NEUROFIBROMATOSIS TYPE-1 GENE; CYCLIC-AMP PATHWAY; SACCHAROMYCES-CEREVISIAE; YEAST; GAP; CLONING; DOMAIN; TRANSFORMATION; INTERACTS AB Proper ras1 function is required for normal sexual function in the yeast Schizosaccharomyces pombe. We have found a gene in S. pombe, sar1, that encodes a product capable of regulating ras1 function. sar1 is a member of an expanding family of RAS GTPase-activating proteins (GAPs) that includes mammalian GAP, the yeast Saccharomyces cerevisiae IRA proteins, and the product of the human neurofibromatosis locus, NF1 sar1, like these other proteins, can complement the loss of IRA function in S. cerevisiae. Computer analysis shows that the highest degree of sequence conservation is restricted to a very small number of diagnostic residues represented by the motif Phe-Leu-Arg-X-X-X-Pro-Ala-X-X-X-Pro. We find no evidence that sar1 is required for the effector function of ras1. C1 NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20209 USA. RP COLD SPRING HARBOR LAB, COLD SPRING HARBOR, NY 11724 USA. OI Wigler, Michael/0000-0003-4396-1971 NR 37 TC 70 Z9 73 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1044-2030 J9 CELL REGUL PD JUN PY 1991 VL 2 IS 6 BP 453 EP 465 PG 13 WC Cell Biology SC Cell Biology GA FV215 UT WOS:A1991FV21500004 PM 1883874 ER PT J AU HEINE, UI BURMESTER, JK FLANDERS, KC DANIELPOUR, D MUNOZ, EF ROBERTS, AB SPORN, MB AF HEINE, UI BURMESTER, JK FLANDERS, KC DANIELPOUR, D MUNOZ, EF ROBERTS, AB SPORN, MB TI LOCALIZATION OF TRANSFORMING GROWTH FACTOR-BETA-1 IN MITOCHONDRIA OF MURINE HEART AND LIVER SO CELL REGULATION LA English DT Article ID FACTOR-BETA; PROTEIN; TGF-BETA-1; EXPRESSION; ANTIBODIES; SEQUENCES; COMPLEX; CELLS AB Using both electron microscopic immunohistochemistry and cell fractionation techniques, we show that transforming growth factor-beta-1 (TGF-beta-1) is found in mitochondria of rat and mouse cardiac myocytes and rat hepatocytes. Four different polyclonal antibodies, raised against various epitopes encompassing the mature portion of the TGF-beta-1 molecule as well as the pro-region of its precursor, were used for the electron microscopy studies. The localization of TGF-beta-1 in mitochondria was confirmed by detection of the native peptide in mitochondria isolated from rat heart and liver; the majority of native TGF-beta-1 found in liver homogenates was recovered in highly pure mitochondrial fractions. The functional role of TGF-beta in the mitochondrion is unknown at present. C1 PROGRAM RESOURCES INC DYNCORP,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. RP HEINE, UI (reprint author), NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892, USA. NR 33 TC 72 Z9 74 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1044-2030 J9 CELL REGUL PD JUN PY 1991 VL 2 IS 6 BP 467 EP 477 PG 11 WC Cell Biology SC Cell Biology GA FV215 UT WOS:A1991FV21500005 PM 1883875 ER PT J AU PAYZA, K RUSSELL, JT AF PAYZA, K RUSSELL, JT TI SODIUM INHIBITS HORMONE-RELEASE AND STIMULATES CALCIUM EFFLUX FROM ISOLATED NERVE-ENDINGS OF THE RAT NEUROHYPOPHYSIS SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE SECRETION; OXYTOCIN; VASOPRESSIN; NEUROSECRETOSOMES; IONOMYCIN ID DIALYZED SQUID AXONS; TRANSMITTER RELEASE; IONS; TERMINALS; CA; SECRETION; EXCHANGE; ABSENCE AB 1. We studied the effects of extracellular sodium on the secretion of vasopressin (VP) and oxytocin (OT) and the efflux of Ca-45 from isolated, perfused nerve endings of the rat neurohypophysis (neurosecretosomes). 2. Upon removal of sodium from the perfusing medium, basal release of VP and OT increased by 3.95 +/- 0.23- and 3.71 +/- 0.22-fold, respectively, followed by a decline to about double the levels in normal (150 mM) sodium (P less-than-or-equal-to 0.1). 3. Compared to neurosecretosomes perfused in normal (150 mM) sodium, omission of sodium from the medium augmented ionomycin-induced VP and OT secretion by 66 +/- 5- and 20 +/- 3-fold, respectively, and A23187-induced secretion was increased 1.3 +/- 0.4- and 1.3 +/- 0.1-fold (P less-than-or-equal-to 0.01 for both ionophores). 4. The inhibition of ionomycin-induced secretion by sodium was concentration dependent (P less-than-or-equal-to 0.01 for sodium greater-than-or-equal-to 5 mM); the IC50 was about 10 mM sodium for both hormones, and the Hill slope was close to -1. 5. The rate of Ca-45 efflux from neurosecretosomes showed 2.7 +/- 0.1-fold stimulation upon increasing sodium from 4.5 to 150 mM (P less-than-or-equal-to 0.01). 6. Our results suggest that sodium inhibits basal and stimulated secretion at the nerve terminal, possibly by reducing intraterminal calcium through sodium/calcium exchange. C1 NICHHD,DEV NEUROBIOL LAB,NEURONAL SECRETORY SYST UNIT,BLDG 36,ROOM B-316,BALTIMORE,MD 21224. NR 24 TC 5 Z9 5 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD JUN PY 1991 VL 11 IS 3 BP 321 EP 331 DI 10.1007/BF00713276 PG 11 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA FV206 UT WOS:A1991FV20600002 PM 1868507 ER PT J AU WINKLERPICKETT, RT YOUNG, HA KUTA, A ORTALDO, JR AF WINKLERPICKETT, RT YOUNG, HA KUTA, A ORTALDO, JR TI ANALYSIS OF RAT NATURAL-KILLER CYTOTOXIC FACTOR (NKCF) - MECHANISM OF ACTION AND RELATIONSHIP TO OTHER CYTOTOXIC CYTOSTATIC FACTORS SO CELLULAR IMMUNOLOGY LA English DT Article ID CYTO-TOXIC FACTORS; SENSITIVE TARGET-CELLS; TUMOR NECROSIS FACTOR; CYTOPLASMIC GRANULES; DNA FRAGMENTATION; CO-CULTURE; RELEASE; LYMPHOTOXIN; INHIBITION; RESISTANT C1 NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. NIH,DCBD,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NR 25 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JUN PY 1991 VL 135 IS 1 BP 42 EP 54 DI 10.1016/0008-8749(91)90252-7 PG 13 WC Cell Biology; Immunology SC Cell Biology; Immunology GA FK345 UT WOS:A1991FK34500004 PM 2018982 ER PT J AU KOBAYASHI, Y OPPENHEIM, JJ MATSUSHIMA, K AF KOBAYASHI, Y OPPENHEIM, JJ MATSUSHIMA, K TI HUMAN PRE-INTERLEUKIN-1-ALPHA AND PRE-INTERLEUKIN-1-BETA - STRUCTURAL FEATURES REVEALED BY LIMITED PROTEOLYSIS SO CHEMICAL & PHARMACEUTICAL BULLETIN LA English DT Article DE PRO-IL-1-ALPHA; PRE-IL-1-BETA; LIMITED PROTEOLYSIS; IMMUNOPRECIPITATION; PROTEOLYTIC PROCESSING; STRUCTURAL STABILIZATION ID HUMAN INTERLEUKIN-1-ALPHA; PRECURSOR; BINDING; IL-1 AB Both pre-interleukin 1-alpha and beta (pre IL 1-alpha and beta) are proteolytically processed into extracellular mature forms of IL 1-alpha and beta. Since pre IL 1-alpha is shown to be biologically active, there may be other reasons for the proteolytic processing of IL 1-alpha and presumably, for IL 1-beta also. In order to examine the possibility that structural stabilization may be associated with the proteolytic processing of pre IL 1-alpha and beta, we investigated the structural features of pre IL 1-alpha and beta by the combination of limited proteolysis and immunoprecipitation with antibodies to the NH2-terminal halves or COOH-terminal halves of pre IL 1-alpha or beta. Both trypsin and V8 protease digested the NH2-terminal halves of pre IL 1-alpha and beta more easily than the COOH-terminal halves of pre IL 1-alpha and beta, yielding structurally stabilized ''mature'' forms of IL 1. Both trypsin and V8 protease yielded a fragment similar in size to mature IL 1-alpha from pre IL 1-alpha. In contrast, trypsin digested pre IL 1-beta into fragments smaller in size than mature IL 1-beta, while V8 protease yielded a fragment similar in size to mature IL 1-beta. Furthermore, mature IL 1-beta, once processed and released from cells, was resistant to trypsin. Since the COOH-terminal half of pre IL 1-beta is more susceptible to protease digestion than the extracellular mature form of IL 1-beta, which consists of the same COOH-half, the proteolytic processing of pre IL 1-beta appears to yield mature IL 1-beta with a more protease-resistant stable tertiary structure. C1 NCI, FREDERICK CANC RES FACIL, DIV CANC TREATMENT, BIOL RESPONSE MODIFIERS PROGRAM, FREDERICK, MD 21701 USA. NR 10 TC 17 Z9 17 U1 0 U2 0 PU PHARMACEUTICAL SOC JAPAN PI TOKYO PA 2-12-15 SHIBUYA, SHIBUYA-KU, TOKYO, 150-0002, JAPAN SN 0009-2363 J9 CHEM PHARM BULL JI Chem. Pharm. Bull. PD JUN PY 1991 VL 39 IS 6 BP 1513 EP 1517 PG 5 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA FV218 UT WOS:A1991FV21800031 PM 1934172 ER PT J AU JOHNSTON, PG LEE, J DOMANSKI, M DRESSLER, F TUCKER, E ROTHENBERG, M CUNNION, RE PIZZO, PA WALSH, TJ AF JOHNSTON, PG LEE, J DOMANSKI, M DRESSLER, F TUCKER, E ROTHENBERG, M CUNNION, RE PIZZO, PA WALSH, TJ TI LATE RECURRENT CANDIDA ENDOCARDITIS SO CHEST LA English DT Note ID INFECTIVE ENDOCARDITIS; CLINICAL-EVALUATION; ECHOCARDIOGRAPHY; DIAGNOSIS AB Late recurrent Candida endocarditis (LRCE) developed on a prosthetic mitral valve 22 months after treatment for primary native mitral valve endocarditis. The LRCE was difficult to diagnose; results of two dimensional echocardiography and repeated blood cultures were negative. Only transesophageal echocardiography revealed a vegetation and only lysis centrifugation blood cultures demonstrated candidemia. Postmortem examination revealed a large Candida vegetation on the prosthetic valve and Candida in the mitral valve ring. This case and a review of the literature indicate that Candida endocarditis treated with amphotericin B and prosthetic valve replacement may recur months after treatment, and that LRCE, which is difficult to diagnose and treat, may be best prevented by lifelong antifungal suppressive therapy. C1 NIH,CTR CLIN,DEPT CLIN CARE MED,BLDG 10,RM 13N240,BETHESDA,MD 20892. NCI,DEPT CARDIOL,MED BRANCH,BETHESDA,MD 20892. NCI,DEPT CARDIOL,PATHOL BRANCH,BETHESDA,MD 20892. NCI,DEPT CARDIOL,PEDIAT BRANCH,BETHESDA,MD 20892. NR 17 TC 43 Z9 43 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JUN PY 1991 VL 99 IS 6 BP 1531 EP 1533 DI 10.1378/chest.99.6.1531 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA FP997 UT WOS:A1991FP99700045 PM 2036848 ER PT J AU MATURI, MF MARTIN, SE MARKLE, D MAXWELL, M BURRUSS, CR SPEIR, E GREENE, R RO, YM VITALE, D GREEN, MV GOLDSTEIN, SR BACHARACH, SL PATTERSON, RE AF MATURI, MF MARTIN, SE MARKLE, D MAXWELL, M BURRUSS, CR SPEIR, E GREENE, R RO, YM VITALE, D GREEN, MV GOLDSTEIN, SR BACHARACH, SL PATTERSON, RE TI CORONARY VASOCONSTRICTION INDUCED BY VASOPRESSIN - PRODUCTION OF MYOCARDIAL-ISCHEMIA IN DOGS BY CONSTRICTION OF NONDISEASED SMALL VESSELS SO CIRCULATION LA English DT Article DE VASOCONSTRICTION; VASOPRESSIN; CORONARY ARTERIES; INTRAMYOCARDIAL PH; MYOCARDIAL ISCHEMIA; LEFT VENTRICULAR EJECTION FRACTION; RADIONUCLIDE ANGIOGRAPHY; IBUPROFEN; PROSTAGLANDINS; CYCLOOXYGENASE BLOCKADE ID PHYSIOLOGICAL USE; CARDIAC-FUNCTION; NEUROPEPTIDE-Y; BLOOD-FLOW; CIRCULATION; ARTERIES; PH; CONSEQUENCES; ANGIOTENSIN; MECHANISM AB Background. We studied the effect of intracoronary administration of arginine-8-vasopressin on blood flow in nondiseased coronary arteries and determined whether this vasoconstriction was severe enough to produce ischemia in 30 dogs. Methods and Results. In group 1 (n = 6), after vasopressin administration coronary blood flow was decreased by 41% (p < 0.002) without changes in heart rate or aortic pressure, and left ventricular ejection fraction measured by radionuclide angiocardiography was decreased by 18% (p < 0.0005). In group 2 (n = 6), ischemia was confirmed by measurement of transmural pH changes. Administration of vasopressin decreased subendocardial pH of the infused zone from 7.40 +/- 0.03 to 7.31 +/- 0.07 (p < 0.01). The subendocardial pH of the zone not infused with vasopressin did not change. To overcome the intrinsic regulation of blood flow, operating primarily in small coronary arteries, we hypothesized that vasopressin must increase resistance primarily in large rather than small coronary arteries. After intracoronary infusion in group 3 (n = 6), however, most (94%) of the increase in resistance during vasopressin administration was explained by an increase of resistance in small coronary arteries. In group 4 (n = 9), vasopressin decreased coronary blood flow by 50% and decreased local shortening by 90% at a time when systemic hemodynamics were unchanged. Coronary constriction induced by vasopressin, or the recovery from it, also was not altered by cyclooxygenase blockade. Conclusions. Thus, vasopressin produces myocardial ischemia by constricting small, nondiseased coronary arteries severly enough to overcome the competition from normal coronary regulation, and this ischemic event is not mediated by prostaglandin products. C1 EMORY UNIV,CRAWFORD LONG HOSP,CARLYLE FRASER HEART CTR,SCH MED,DIV CARDIOL,550 PEACHTREE ST,ATLANTA,GA 30365. NHLBI,CARDIOL BRANCH,EXPTL PHYSIOL & PHARMACOL SECT,BETHESDA,MD 20892. NIH,CTR CLIN,BETHESDA,MD 20892. NIH,DEPT NUCL MED,BETHESDA,MD 20892. NIH,DIV RES SERV,BETHESDA,MD 20892. NIH,BIOMED ENGN & INSTRUMENTAT BRANCH,BETHESDA,MD 20892. FU NHLBI NIH HHS [HL-34558] NR 40 TC 56 Z9 60 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN PY 1991 VL 83 IS 6 BP 2111 EP 2121 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA FP800 UT WOS:A1991FP80000030 PM 1904014 ER PT J AU DANZIGER, RS SAKAI, M CAPOGROSSI, MC SPURGEON, HA HANSFORD, RG LAKATTA, EG AF DANZIGER, RS SAKAI, M CAPOGROSSI, MC SPURGEON, HA HANSFORD, RG LAKATTA, EG TI ETHANOL ACUTELY AND REVERSIBLY SUPPRESSES EXCITATION CONTRACTION COUPLING IN CARDIAC MYOCYTES SO CIRCULATION RESEARCH LA English DT Article DE ETHANOL; SINGLE ISOLATED CARDIAC MYOCYTES; CONTRACTILITY; CYTOSOLIC CALCIUM; FLUORESCENT CA2+ PROBES; INDO-1; QUIN-2 ID ISOLATED RAT-HEART; SARCOPLASMIC-RETICULUM; PROTEIN-KINASE; CALCIUM-UPTAKE; CA-2+ RELEASE; MUSCLE; CELLS; ACETALDEHYDE; MECHANISM; MEMBRANES AB We used adult rat cardiac myocytes to examine the acute effects of 0.1-5.0% (vol/vol) ethanol (ETOH) on 1) the cytosolic [Ca2+] (Ca(i)) transient measured as the change in indo 1 fluorescence at 410/490 nm and contraction elicited by electrical stimulation of single cells and 2) the sarcoplasmic reticulum (SR) Ca2+ content in cell suspensions. During stimulation at 1 Hz, clinically relevant ETOH correlations (0.1-0.15% [vol/vol]) caused a 10-15% decrease in the contraction amplitude, measured by myocyte edge tracking, without decreasing the Ca(i) transient that initiates contraction. At higher ETOH concentrations (1-5% [vol/vol]), ETOH caused profound contractile depression and also reduced the magnitude of the Ca(i) transient. These effects were reversed within minutes of ETOH washout. Addition of norepinephrine (10-mu-M) to the bathing solution or an increase in bathing [Ca2+] in the continued presence of ETOH could also reverse its effects. The relation of the amplitude of the Ca(i) transient to the contraction amplitude measured across a range of bathing [Ca2+] was shifted by ETOH, such that for a given Ca(i) transient a marked reduction in contraction amplitude occurred. In unstimulated myocyte suspensions, ETOH (1-5% [vol/vol]) caused a concentration-dependent depletion of SR Ca2+ content, manifested as a diminution in the Ca(i) increase elicited by caffeine in the presence of extracellular EGTA and no added Ca2+. Thus, in rat cardiac myocytes a reduction in the myofilament Ca2+ response, possibly due to a decrease in myofilament Ca2+ sensitivity, is a mechanism for contractile depression due to clinically relevant ETOH concentrations. Higher concentrations of ETOH cause further contractile depression, in part, by inducing SR Ca2+ release and depleting the SR of Ca2+, leading to an attenuation of the Ca(i) transient elicited by electrical stimulation, and by further depressing the myofilament length-Ca2+ relation. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224. NR 41 TC 75 Z9 78 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUN PY 1991 VL 68 IS 6 BP 1660 EP 1668 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA FP119 UT WOS:A1991FP11900017 PM 2036717 ER PT J AU MARAIA, R SAAL, HM WANGSA, D AF MARAIA, R SAAL, HM WANGSA, D TI A CHROMOSOME-17Q DENOVO PARACENTRIC INVERSION IN A PATIENT WITH CAMPOMELIC DYSPLASIA - CASE-REPORT AND ETIOLOGIC HYPOTHESIS SO CLINICAL GENETICS LA English DT Article DE CAMPOMELIC DYSPLASIA; CHROMOSOME-17Q; COL1A1; HOMEOBOX GENE; HOX-2, SKELETAL DYSPLASIA; TYPE-I COLLAGEN GENE ID H-Y-ANTIGEN; SYNDROME TYPE-VII; HOMEO BOX GENE; CAMPTOMELIC DWARFISM; SEX REVERSAL; COLLAGEN ALLELE; EXPRESSION; MURINE; FEMALE; HETEROGENEITY AB The campomelic syndrome is a skeletal dysplasia with a characteristic pattern of deformity involving the proximal and distal extremities, pelvic and shoulder girdles, thoracic cage and palate. Respiratory compromise often leads to death in early infancy. Etiology has not been determined although evidence suggests genetic heterogeneity in patients with campomelia. Cytogenetic analyses in the past have revealed an unexpectedly high incidence of a 46,XY karyotype in phenotypic females. We report here on a patient with a typical case of campomelic dysplasia in whom a de novo paracentric inversion of chromosome 17q was identified. Review of the genetic map of the inverted region identified potential "structural" genes including the Hox-2-homeobox gene and the collagen gene, COLlAl, which may be involved in the pathogenesis genesis of campomelic syndrome. C1 CHILDRENS HOSP,NATL MED CTR,DEPT MED GENET,WASHINGTON,DC 20010. RP MARAIA, R (reprint author), NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892, USA. NR 44 TC 34 Z9 34 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD JUN PY 1991 VL 39 IS 6 BP 401 EP 408 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA FT399 UT WOS:A1991FT39900001 PM 1677832 ER PT J AU KLEINMAN, DV SWANGO, PA NIESSEN, LC AF KLEINMAN, DV SWANGO, PA NIESSEN, LC TI EPIDEMIOLOGIC STUDIES OF ORAL MUCOSAL CONDITIONS - METHODOLOGIC ISSUES SO COMMUNITY DENTISTRY AND ORAL EPIDEMIOLOGY LA English DT Review DE EPIDEMIOLOGY, ORAL; INCIDENCE; METHODOLOGY; ORAL MUCOSAL LESIONS; PREVALENCE ID PRE-CANCEROUS LESIONS; LICHEN PLANUS; INDIAN VILLAGERS; CANDIDA-ALBICANS; NATURAL-HISTORY; APHTHOUS ULCERS; TOBACCO HABITS; FOLLOW-UP; PREVALENCE; LEUKOPLAKIA AB The methods used in the international English-language literature of epidemiologic investigations of oral mucosal conditions were reviewed. Methods used to study leukoplakia, lichen planus, recurrent herpes labialis, recurrent aphthous ulcers, geographic tongue and candidiasis are highlighted. In addition, studies of the full range of pathologies documented in a population were reviewed. The methodologic issues raised by the epidemiologic literature as well as those to be considered for future studies of oral mucosal conditions are presented. Emphasis is placed on study population selection, diagnostic criteria development, type and training of examiners, risk factor assessment and issues related to data collection, analysis and reporting. C1 VET ADM MED CTR,GERIATR DENT PROGRAM,PERRY POINT,MD 21902. RP KLEINMAN, DV (reprint author), NIDR,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,WESTWOOD BLDG,ROOM 549,BETHESDA,MD 20892, USA. NR 119 TC 49 Z9 49 U1 1 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0301-5661 J9 COMMUNITY DENT ORAL JI Community Dentist. Oral Epidemiol. PD JUN PY 1991 VL 19 IS 3 BP 129 EP 140 DI 10.1111/j.1600-0528.1991.tb00128.x PG 12 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA FT689 UT WOS:A1991FT68900001 PM 1864064 ER PT J AU BRINTON, LA AF BRINTON, LA TI ORAL-CONTRACEPTIVES AND CERVICAL NEOPLASIA SO CONTRACEPTION LA English DT Article ID HUMAN PAPILLOMAVIRUS INFECTION; LOS-ANGELES-COUNTY; LONG-TERM USE; UTERINE CERVIX; RISK-FACTORS; CARCINOMA-INSITU; YOUNG-WOMEN; MICROGLANDULAR HYPERPLASIA; SEXUAL-ACTIVITY; GENITAL-TRACT AB Although initial studies examining the relationship of oral contraceptives to risk of cervical neoplasia were reassuring, more recent studies provide some evidence of a positive relationship, particularly for long-term usage. Results, however, are difficult to interpret, because of a variety of methodologic complexities, including potential sources of confounding and bias. Sexual behavior and Pap smear screening have been identified as important confounders, but in several well-controlled studies residual excess risks of nearly 2-fold persist for users of 5 or more years. A possible promotional effect of oral contraceptives is suggested by higher risks associated with recent usage. There also is some suggestion of a stronger effect for adenocarcinomas than for squamous cell tumors. A relationship is biologically possible, given findings of hormone receptors in cervical tissue and the fact that oral contraceptives have been found to induce cervical hyperplasia. In addition, oral contraceptives may induce proliferation of the human papillomaviruses, the leading suspect agent for cervical cancer. Although a number of lines of evidence support a relationship of oral contraceptives to cervical cancer risk, firm conclusions await the results of additional studies that specifically address some of the methodologic shortcomings of previous investigations. In particular, additional follow-up studies are needed to define the effect of oral contraceptives on the natural history of cervical lesions. RP BRINTON, LA (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EXECUT PLAZA N,RM 443,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 66 TC 64 Z9 66 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0010-7824 J9 CONTRACEPTION JI Contraception PD JUN PY 1991 VL 43 IS 6 BP 581 EP 595 DI 10.1016/0010-7824(91)90005-Z PG 15 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA FP962 UT WOS:A1991FP96200005 PM 1868734 ER PT J AU AZEN, SP BOONE, DC BARLOW, W MCCUEN, BW WALONKER, AF ANDERSON, MM LEAN, JS MOWERY, RL RYAN, SJ STERN, W AF AZEN, SP BOONE, DC BARLOW, W MCCUEN, BW WALONKER, AF ANDERSON, MM LEAN, JS MOWERY, RL RYAN, SJ STERN, W TI METHODS, STATISTICAL FEATURES, AND BASE-LINE RESULTS OF A STANDARDIZED, MULTICENTERED OPHTHALMOLOGIC SURGICAL TRIAL - THE SILICONE STUDY SO CONTROLLED CLINICAL TRIALS LA English DT Article DE CLINICAL TRIAL; SURGICAL TRIAL; OPHTHALMOLOGY; CROSSOVER DESIGN ID ADVANCED PROLIFERATIVE VITREORETINOPATHY; SULFUR-HEXAFLUORIDE GAS; RETINAL-DETACHMENT; VITREOUS SURGERY; PERFLUOROCARBON GASES; OIL; VITRECTOMY; MANAGEMENT; COMPLICATIONS; RETRACTION AB This article describes the trial design and baseline results for the Silicone Study, a multicenter, randomized surgical trial designed to compare the effectiveness of silicone fluid versus long-acting gas in the treatment of proliferative vitreoretinopathy (PVR). Design features include (1) standardization of the surgical protocol to reduce intersurgeon variability, (2) formulation of a PVR clinical classification system relevant to modern vitreoretinal surgery, and (3) creation of a photographic protocol to document PVR pathology. Statistical issues affecting the analysis of the outcome data include (1) the addition of a second group of patients with more severely diseased eyes after the trial began, (2) the change of a different long-acting gas during the course of the trial, and (3) recurrent retinal detachments that require reoperations with the randomized treatment, and, in some instances, a crossover from the randomized to the alternate treatment. Demographic and baseline ocular characteristics are presented for the two groups under study. C1 DUKE UNIV,NEI,DURHAM,NC 27706. UNIV SO CALIF,DEPT OPHTHALMOL,LOS ANGELES,CA 90089. UNIV CALIF SAN FRANCISCO,DEPT OPHTHALMOL,SAN FRANCISCO,CA 94143. GRP HLTH COOPERAT PUGET SOUND,CTR HLTH STUDIES,SEATTLE,WA. GRP HLTH COOPERAT PUGET SOUND,DEPT PREVENT MED,SEATTLE,WA. GRP HLTH COOPERAT PUGET SOUND,DEPT OPHTHALMOL,SEATTLE,WA. FU NEI NIH HHS [EY05571] NR 44 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD JUN PY 1991 VL 12 IS 3 BP 438 EP 455 DI 10.1016/0197-2456(91)90022-E PG 18 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA FN559 UT WOS:A1991FN55900008 PM 1651213 ER PT J AU Wolffe, AP AF Wolffe, Alan P. TI RNA polymerase III transcription SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article AB Remarkable progress has been made in defining the functional significance of the protein-DNA interactions involved in transcription complex formation on yeast tRNA and 55 RNA genes. This new information leads to a re-evaluation of how the class III gene transcription machinery operates. C1 [Wolffe, Alan P.] NIH, Bethesda, MD 20892 USA. RP Wolffe, AP (reprint author), NICHD, Mol Embryol Lab, NIH, Bldg 6,Room 131, Bethesda, MD 20891 USA. NR 36 TC 14 Z9 14 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 EI 1879-0410 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD JUN PY 1991 VL 3 IS 3 BP 461 EP 466 DI 10.1016/0955-0674(91)90074-9 PG 6 WC Cell Biology SC Cell Biology GA V39FY UT WOS:000209398100009 PM 1892658 ER PT J AU VANSEVENTER, GA SHIMIZU, Y SHAW, S AF VANSEVENTER, GA SHIMIZU, Y SHAW, S TI ROLES OF MULTIPLE ACCESSORY MOLECULES IN T-CELL ACTIVATION SO CURRENT OPINION IN IMMUNOLOGY LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-1; RESTING B-CELLS; ADHESION MOLECULE-1; COGNATE INTERACTIONS; LYMPHOCYTES-T; CD4 CELLS; IFN-GAMMA; RECEPTOR; FIBRONECTIN; HELPER AB Accessory molecules expressed on T cells can mediate adhesion between T cells and other cells, or the extracellular matrix. The same T-cell accessory molecules participate in a dialogue with their ligands (counter-receptors) on the antigen-presenting cells, and elicit signals that determine the specifics of activation and subsequent differentiation of the T cells and antigen-presenting cells. C1 UNIV MICHIGAN,DEPT MICROBIOL & IMMUNOL,ANN ARBOR,MI 48109. RP VANSEVENTER, GA (reprint author), NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892, USA. OI Shimizu, Yoji/0000-0001-9760-0288 NR 63 TC 185 Z9 186 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 1991 VL 3 IS 3 BP 294 EP 303 DI 10.1016/0952-7915(91)90027-X PG 10 WC Immunology SC Immunology GA FV446 UT WOS:A1991FV44600003 PM 1910606 ER PT J AU POLTE, T NEWMAN, W RAGHUNATHAN, G GOPAL, TV AF POLTE, T NEWMAN, W RAGHUNATHAN, G GOPAL, TV TI STRUCTURAL AND FUNCTIONAL-STUDIES OF FULL-LENGTH VASCULAR CELL-ADHESION MOLECULE-1 - INTERNAL DUPLICATION AND HOMOLOGY TO SEVERAL ADHESION PROTEINS SO DNA AND CELL BIOLOGY LA English DT Article ID DIRECT EXPRESSION CLONING; TUMOR NECROSIS FACTOR; ENDOTHELIAL-CELLS; MAMMALIAN-CELLS; DNA; INTERLEUKIN-1; NEUTROPHILS; STIMULATION; LYMPHOCYTES; SIMILARITY AB Full-length vascular cell adhesion molecule-1 (VCAM-1) cDNA cloned by polymerase chain reaction (PCR) of poly(A)+RNA from interleukin-1 (IL-1)-activated human umbilical vein endothelial cells (HUVEC) contained an insert of 276 nucleotides after position 1,034 of the previously published sequence. Synthetic oligomer probes, specific for each of the two possible species of VCAM-1 mRNA, detected only the longer form of VCAM-1 by Northern analysis of activated endothelial cell mRNA. This full-length VCAM-1 contains two internally repeated domains of approximately 273 amino acids with a high degree of homology. This new sequence information reveals homologies with additional members of the immunoglobulin superfamily and improves ALIGN scores for previously cited adhesion proteins. Removal of the transmembrane domain and the carboxy-terminal end of the full-length VCAM-1 molecule allows the molecule to be secreted into the culture medium from cells transfected with an expression vector containing the corresponding VCAM-1 cDNA. C1 OTSUKA AMER PHARMACEUT INC,MARYLAND RES LABS,9900 MED CTR DR,ROCKVILLE,MD 20850. NCI,MATH BIOL LAB,BETHESDA,MD 20892. NR 34 TC 44 Z9 45 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD JUN PY 1991 VL 10 IS 5 BP 349 EP 357 DI 10.1089/dna.1991.10.349 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA FT220 UT WOS:A1991FT22000004 PM 1713772 ER PT J AU ORBAN, L CHRAMBACH, A ZWIEB, C ADHYA, SL AF ORBAN, L CHRAMBACH, A ZWIEB, C ADHYA, SL TI DETECTION OF CONFORMATIONAL AND NET CHARGE DIFFERENCES IN DNA-PROTEIN COMPLEXES BY QUANTITATIVE ELECTROPHORESIS ON POLYACRYLAMIDE-AGAROSE COPOLYMER GELS SO ELECTROPHORESIS LA English DT Article ID SITE-SPECIFIC RECOMBINATION; INTEGRATION HOST FACTOR; ESCHERICHIA-COLI; REGULATORY PROTEINS; REPLICATION ORIGIN; GAL; APPARATUS; PARTICLES; BINDING; VECTOR AB The Galactosidase repressor (GalR) of Escherichia coli modulates the expression of the gal operon by binding to two DNA operators, O(E) and O(I). The O(E) and O(I) elements are 16 bp pallindromic DNA sequences, differing in four of the base pairs (Fig. 1). 0(E) and O(I) DNA fragments, both free and complexed with repressor, were analyzed by "quantitative gel electrophoresis". By the criteria of that method, applied to the linear Ferguson plots of both DNA fragments and the linear ranges of those of the DNA-GalR complexes, it was shown that the apparent size of DNA increases upon repressor binding. Moreover, this size increase is greater for the complex with the O(I) operator than for the complex with the O(E) operator in the case that GalR is located in the center of a 155 bp DNA fragment. This is not the case when GalR is located in a peripheral position. By contrast with their size differences, the centrally located GalR-O(I) and GalR-O(E) complexes appear to possess indistinguishable net surface charge densities as judged from the intercepts with the mobility axis. The larger size of the complex with centrally located O(I) fragment, as compared with that bearing the O(E) fragment, is interpreted as being due to bending of the DNA-protein complex, since an authentically bent fragment of a plasmid with bent upstream activator sequence also exhibits a larger slope of the Ferguson plot, and thus the larger size, than predicted on the basis of its DNA chain length (bp). Thus, the apparently larger size of the GalR-O(I) complex at the center of DNA, compared to that of the GalR-O(E) complex, supports the previous conclusion that the Gal repressor induces a larger degree of bending in O(I) DNA than in O(E) DNA. DNA fragments bearing O(E) and O(I) when complexed with the Gal repressor show convex Ferguson plots at polyacrylamide concentrations below that of gelation and in the presence of 0.5 % agarose, while the plots of the corresponding free 155 bp DNA fragments are linear in that range. The curvature presumably reflects the size increase concomitant with complex formation, since DNA larger than 155 bp also exhibits that curvature on polyacrylamide stabilized by nonrestrictive agarose gels. C1 NICHHD,THEORET & PHYS BIOL LAB,MACROMOLEC ANAL SECT,BLDG 10,RM 6C101,BETHESDA,MD 20892. AGR BIOTECHNOL CTR,INST MOLEC GENET,GODOLLO,HUNGARY. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. OI Orban, Laszlo/0000-0001-5435-5948 NR 39 TC 2 Z9 2 U1 0 U2 2 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 JUN PY 1991 VL 12 IS 6 BP 391 EP 396 DI 10.1002/elps.1150120602 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA FW847 UT WOS:A1991FW84700001 PM 1889387 ER PT J AU GERSTEN, DM RODRIGUEZ, LV GEORGE, DG JOHNSTON, DA ZAPOLSKI, EJ AF GERSTEN, DM RODRIGUEZ, LV GEORGE, DG JOHNSTON, DA ZAPOLSKI, EJ TI ON THE RELATIONSHIP OF AMINO-ACID-COMPOSITION TO SILVER STAINING OF PROTEINS IN ELECTROPHORESIS GELS .2. PEPTIDE SEQUENCE-ANALYSIS SO ELECTROPHORESIS LA English DT Article ID COOMASSIE BRILLIANT BLUE; POLYACRYLAMIDE GELS; ENHANCEMENT; MECHANISM AB The quantification of proteins in silver-stained electrophoresis gels has been limited by the differences in "stainability" of different proteins. Despite efforts by many researchers, the precise basis of the reaction between silver reagents and polypeptides is still unclear, and, depending on the formulation, may even differ. We have tested the hypothesis that differences in stainability among proteins can be attributed to differences in di- or tripeptide composition. The results indicate that some order of protein structure other than short peptides accounts for the staining differences observed. C1 UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT MOLEC PATHOL,HOUSTON,TX 77030. GEORGETOWN UNIV,MED CTR,NATL BIOMED RES FDN,WASHINGTON,DC 20007. UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT BIOMATH,HOUSTON,TX 77030. NIH,DIV RES GRANTS,BETHESDA,MD 20892. RP GERSTEN, DM (reprint author), GEORGETOWN UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20007, USA. NR 22 TC 11 Z9 11 U1 0 U2 2 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 JUN PY 1991 VL 12 IS 6 BP 409 EP 414 DI 10.1002/elps.1150120605 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA FW847 UT WOS:A1991FW84700004 PM 1716197 ER PT J AU CHU, CS TRAPNELL, BC MURTAGH, JJ MOSS, J DALEMANS, W JALLAT, S MERCENIER, A PAVIRANI, A LECOCQ, JP CUTTING, GR GUGGINO, WB CRYSTAL, RG AF CHU, CS TRAPNELL, BC MURTAGH, JJ MOSS, J DALEMANS, W JALLAT, S MERCENIER, A PAVIRANI, A LECOCQ, JP CUTTING, GR GUGGINO, WB CRYSTAL, RG TI VARIABLE DELETION OF EXON-9 CODING SEQUENCES IN CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR GENE MESSENGER-RNA TRANSCRIPTS IN NORMAL BRONCHIAL EPITHELIUM SO EMBO JOURNAL LA English DT Article DE CYSTIC FIBROSIS; EPITHELIUM; HUMAN; LUNG; MESSENGER RNA SPLICING ID NUCLEOTIDE-BINDING FOLD; PROTEIN KINASE-C; CHLORIDE CHANNELS; IDENTIFICATION; MUTATIONS; DNA; TRANSPORT AB The predicted protein domains coded by exons 9-12 and 19-23 of the 27 exon cystic fibrosis transmembrane conductance regulator (CFTR) gene contain two putative nucleotide-binding fold regions. Analysis of CFTR and mRNA transcripts in freshly isolated bronchial epithelium from 12 normal adult individuals demonstrated that all had some CFTR mRNA transcripts with exon 9 completely deleted (exon 9- mRNA transcripts). In most (9 of 12), the exon 9- transcripts represented less-than-or-equal-to 25% of the total CFTR transcripts. However, in three individuals, the exon 9- transcripts were more abundant, comprising 39, 62 and 66% of all CFTR transcripts. Re-evaluation of the same individuals 2-4 months later showed the same proportions of exon 9- transcripts. Of the 24 CFTR alleles in the 12 individuals, the sequences of the exon-intron junctions relevant to exon 9 deletion (exon 8-intron 8, intron 8-exon 9, exon 9-intron 9, and intron 9-exon 10) were identical except for the intron 8-exon 9 region sequences. Several individuals had varying lengths of a TG repeat in the region between splice branch and splice acceptor consensus sites. Interestingly, one allele in each of the two individuals with 62 and 66% exon 9- transcripts had a TT deletion in the splice acceptor site for exon 9. These observations suggest either the unlikely possibility that sequences in exon 9 are not critical for the functioning of the CFTR or that only a minority of the CFTR mRNA transcripts need to contain exon 9 sequences to produce sufficient amounts of a normal CFTR to maintain a normal clinical phenotype. C1 NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892. TRANSGENE SA,STRASBOURG,FRANCE. JOHNS HOPKINS UNIV HOSP,DEPT PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV HOSP,CTR MED GENET,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21205. RP CHU, CS (reprint author), NHLBI,PULM BRANCH,BLDG 10,ROOM 6D03,BETHESDA,MD 20892, USA. NR 33 TC 131 Z9 134 U1 1 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JUN PY 1991 VL 10 IS 6 BP 1355 EP 1363 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FL651 UT WOS:A1991FL65100009 PM 1709095 ER PT J AU BAGNATO, A MORETTI, C FRAJESE, G CATT, KJ AF BAGNATO, A MORETTI, C FRAJESE, G CATT, KJ TI GONADOTROPIN-INDUCED EXPRESSION OF RECEPTORS FOR GROWTH-HORMONE RELEASING-FACTOR IN CULTURED GRANULOSA-CELLS SO ENDOCRINOLOGY LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; VASOACTIVE INTESTINAL PEPTIDE; ADENYLATE-CYCLASE; VIP RECEPTORS; RAT PLACENTA; CYCLIC-AMP; DIFFERENTIATION; ADENOSINE-3',5'-MONOPHOSPHATE; STEROIDOGENESIS; INDUCTION AB The hypothalamic neuropeptide, GRF, is formed in the ovary and acts via specific receptors in granulosa cells to enhance cAMP production and steroidogenic responses to the pituitary gonadotropin, FSH. Granulosa cells cultured without hormonal treatment displayed low levels of binding sites for GRF and the related neuropeptide, vasoactive intestinal peptide. However, treatment with increasing concentrations (50-500 ng/ml) of FSH caused dose-dependent increases in cAMP production and expression of binding sites measured with radioiodinated [His1, Nle27] human GRF(1-32)NH2, with no change in binding affinity. The maximum increase in GRF binding sites (2.2-fold) was elicited by 250 ng/ml FSH after 72 h incubation. GRF binding sites were also increased by agents that elevate intracellular cAMP, including choleragen, vasoactive intestinal peptide, dibutyryl cAMP, and forskolin. Low doses of forskolin that did not alone increase [I-125][His1,Nle27] human GRF(1-32)NH2 binding potentiated the action of FSH on GRF binding sites, but the effects of maximal stimulatory doses of both agents were not additive. These findings demonstrate that FSH promotes the expression of GRF receptors in maturing granulosa cells through cAMP-dependent mechanisms. Since GRF enhances the actions of FSH on cAMP production and granulosa cell differentiation, and GRF receptors are increased by the cAMP-mediated actions of FSH, locally produced GRF could exert a positive autoregulatory action to accelerate follicular maturation by amplifying the granulosa cell response to FSH. C1 NICHHD, ENDOCRINOL & REPROD RES BRANCH, BLDG 10, ROOM B1-L400, BETHESDA, MD 20892 USA. UNIV ROME LA SAPIENZA, MED CLIN 5, I-00161 ROME, ITALY. RI Bagnato, Anna/G-9747-2016; OI Bagnato, Anna/0000-0002-7269-9522; MORETTI, COSTANZO/0000-0003-4006-2575 NR 35 TC 29 Z9 29 U1 0 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1991 VL 128 IS 6 BP 2889 EP 2894 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FN112 UT WOS:A1991FN11200029 PM 1674686 ER PT J AU ERICKSON, JD MASSERANO, JM ZOELLER, RT ESKAY, RL WEINER, N AF ERICKSON, JD MASSERANO, JM ZOELLER, RT ESKAY, RL WEINER, N TI DIFFERENTIAL RESPONSIVENESS OF THE PITUITARY-THYROID AXIS TO THYROTROPIN-RELEASING-HORMONE IN MOUSE LINES SELECTED TO DIFFER IN CENTRAL-NERVOUS-SYSTEM SENSITIVITY TO ETHANOL SO ENDOCRINOLOGY LA English DT Article ID RAT-BRAIN; SS MICE; SYMPATHETIC NEUROTRANSMISSION; PARAVENTRICULAR NUCLEUS; GENE-EXPRESSION; LONG-SLEEP; TRH; LS; MATURATION; HYPOTHALAMUS AB Long-sleep (LS) and short sleep (SS) mice are genetic lines that differ in central nervous system sensitivity to ethanol. The possible role of TRH in mediating the difference in the thyroid status between these two lines was investigated. An increase in TRH gene expression in the paraventricular nucleus and TRH peptide levels in the hypothalamus between postnatal days 8-14 in both SS and LS mice coincided with increased circulating levels of thyroxine during this critical period of central nervous system development. No significant differences in TRH biosynthesis were observed between LS and SS mice during this time. Exogenous administration of TRH to LS and SS mice on day 8, when endogenous serum thyroxine levels were equivalent, resulted in a greater increase in serum thyroxine in SS mice (150%) than LS mice (51%). The differential response to the TRH stimulation test was also present on day 14 (SS, 43%; LS, 18%). The differential responsiveness of the pituitary-thyroid axis to exogenous TRH paralleled the differential increase in endogenous serum thyroxine observed between day 8 and 14 in these mice. Administration of TRH to day 20 and adult (60 days) LS and SS mice resulted in nearly equivalent (approximately 75%) increases in free thyroxine serum levels, yet the magnitude of thyroxine release was 50% greater in SS mice, due perhaps to between-line differences within the thyroid glands. It is unlikely that dissimilar endogenous levels of TRH account for the intrinsic difference in the thyroid status in LS and SS mice. Instead, the increased pituitary-thyroid responsiveness to TRH in SS mice during the second postnatal week may translate into increased functional capacity of the thyroid gland in adult SS relative to LS mice. C1 UNIV COLORADO, SCH MED, DEPT PHARMACOL, DENVER, CO 80202 USA. UNIV MISSOURI, MED CTR, SCH MED, DEPT ANAT, COLUMBIA, MO 65201 USA. NIAAA, CLIN STUDIES LAB, BETHESDA, MD USA. RP NIMH, ALCOHOL DRUG ABUSE & MENTAL HLTH ADM, CELL BIOL LAB, BETHESDA, MD 20892 USA. FU NIAAA NIH HHS [AA-03527] NR 59 TC 2 Z9 2 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1991 VL 128 IS 6 BP 3013 EP 3020 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FN112 UT WOS:A1991FN11200045 PM 1903698 ER PT J AU ISOZAKI, O TSUSHIMA, T EMOTO, N SAJI, M TSUCHIYA, Y DEMURA, H SATO, Y SHIZUME, K KIMURA, S KOHN, LD AF ISOZAKI, O TSUSHIMA, T EMOTO, N SAJI, M TSUCHIYA, Y DEMURA, H SATO, Y SHIZUME, K KIMURA, S KOHN, LD TI METHIMAZOLE REGULATION OF THYROGLOBULIN BIOSYNTHESIS AND GENE-TRANSCRIPTION IN RAT FRTL-5 THYROID-CELLS SO ENDOCRINOLOGY LA English DT Article ID GROWTH FACTOR-I; THYROTROPIN REGULATION; PROTEIN-SYNTHESIS; RIBONUCLEIC-ACID; CYCLIC-AMP; IODINE; EXPRESSION; PROMOTER; HORMONE; ADENOSINE-3',5'-MONOPHOSPHATE AB Methimazole (MMI) increases thyroglobulin (Tg) mRNA levels in FRTL-5 rat thyroid cells. The increase reflects a transcriptional action of the antithyroid agent and is inhibited by cycloheximide, as is the transcriptional action of TSH. It takes several hours to be apparent, is maximal between 24-48 h, and is specific, in that thyroid peroxidase and beta-actin mRNA levels are not increased simultaneously. The increased mRNA levels are associated with increased recovery of immunoprecipitable Tg in the medium of cells exposed to [S-35]methionine. The MMI effect appears to be independent of the action of TSH or its cAMP signal, since the MMI-induced increase in Tg mRNA levels is evident in cells treated with TSH or maintained in its absence and is associated not with increases in cAMP levels but, rather, under some circumstances with a decrease. The effect is evident under conditions in which the ability of insulin or insulin-like growth factor-I to increase Tg mRNA levels is already maximal. The MMI-induced increase is inhibited by concentration of iodide associated with autoregulation of FRTL-5 rat thyroid cells, is inhibited but not mimicked by propylthiouracil, and is not altered by T3. The increase in Tg mRNA levels does not correlate with increased DNA synthesis as a function of MMI concentration either in cells treated with TSH or in those maintained in its absence. A concentration of MMI (5 mM) that increases Tg mRNA levels can also inhibit 8-bromo-cAMP- or phorbol ester-induced increases in [H-3]thymidine incorporation into DNA. C1 INST GROWTH SCI,SHINJUKU KU,TOKYO 162,JAPAN. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892. RP ISOZAKI, O (reprint author), TOKYO WOMENS MED COLL,INST CLIN ENDOCRINOL,DEPT MED,8-1 KAWADACHO,SHINJUKU KU,TOKYO 162,JAPAN. RI Saji, Motoyasu/E-4007-2011 NR 45 TC 18 Z9 18 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1991 VL 128 IS 6 BP 3113 EP 3121 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FN112 UT WOS:A1991FN11200057 PM 1645261 ER PT J AU BEGEOT, M LANGLOIS, D SPIEGEL, AM SAEZ, JM AF BEGEOT, M LANGLOIS, D SPIEGEL, AM SAEZ, JM TI REGULATION OF GUANINE-NUCLEOTIDE BINDING REGULATORY PROTEINS IN CULTURED ADRENAL-CELLS BY ADRENOCORTICOTROPIN AND ANGIOTENSIN-II SO ENDOCRINOLOGY LA English DT Article ID INDUCED CAMP PRODUCTION; GROWTH FACTOR-I; ADENYLATE-CYCLASE; ALPHA-SUBUNIT; PHORBOL ESTER; BETA-SUBUNIT; HORMONAL-REGULATION; MESSENGER-RNA; GS-ALPHA; RAT AB In addition to their steroidogenic effect on cultured bovine adrenal fasciculata cells ACTH and angiotensin-II (A-II) have a long term effect on the ability of these cells to respond to subsequent hormonal stimulation. The present work explores the effects of a 72-h pretreatment of adrenal cells with both hormones on the first steps of the mechanism of action of ACTH and A-II and on the amounts of the alpha-subunits of guanine nucleotide binding proteins Gs and Gi. ACTH but not A-II increased acute ACTH or cholera toxin-induced cAMP production. Moreover, ACTH but not A-II enhanced the amount of alpha-s protein evaluated by cholera toxin ADP ribosylation, whereas both hormones elevated immunoblotted alpha-s. Both hormones increased A-II-induced phosphoinositide breakdown and Ca2+ uptake without modification of the A-II-potentiating effect on ACTH-induced cAMP production. Treatment of cells with pertussis toxin (PT, 0.5-mu-g/ml) for the last 24 h reduced by 27% the A-II-induced phosphoinositide breakdown in A-II-pretreated cells but had no significant effect in ACTH-pretreated cells. No effect of PT was observed on A-II-induced Ca2+ uptake or on its potentiating action on ACTH-induced cAMP production in ACTH as well as A-II-pretreated cells. Moreover, both hormones increased Gi proteins (40-41 kDa) evaluated by PT ADP ribosylation. Immunoblot analysis revealed that ACTH preferentially enhanced alpha-i3, whereas the stimulatory effect of A-II was more marked on alpha-i1 and alpha-i2. These results indicate that in bovine adrenal fasciculata cells, peptide hormones settle target cell responsiveness not only by regulating the membrane-bound receptors, but also by modulating the level of G proteins coupling these receptors to the intracellular signals. C1 HOP DEBROUSSE,INSERM,U307,29 RUE SOEUR BOUVIER,F-69322 LYONS 05,FRANCE. NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BETHESDA,MD 20892. NR 47 TC 25 Z9 25 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1991 VL 128 IS 6 BP 3162 EP 3168 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FN112 UT WOS:A1991FN11200063 PM 1645263 ER PT J AU APPEL, NM OWENS, MJ CULP, S ZACZEK, R CONTRERA, JF BISSETTE, G NEMEROFF, CB DESOUZA, EB AF APPEL, NM OWENS, MJ CULP, S ZACZEK, R CONTRERA, JF BISSETTE, G NEMEROFF, CB DESOUZA, EB TI ROLE FOR BRAIN CORTICOTROPIN-RELEASING FACTOR IN THE WEIGHT-REDUCING EFFECTS OF CHRONIC FENFLURAMINE TREATMENT IN RATS SO ENDOCRINOLOGY LA English DT Article ID BROWN ADIPOSE-TISSUE; SYMPATHETIC FIRING RATE; CENTRAL NERVOUS-SYSTEM; HYPOTHALAMOPITUITARY-ADRENAL AXIS; FA FA RATS; FACTOR CRF; PARAVENTRICULAR NUCLEUS; BODY-WEIGHT; FOOD-INTAKE; ZUCKER RAT AB Fenfluramine is an amphetamine derivative which is used as a weight-reducing agent in the treatment of obesity. It has been postulated that fenfluramine affects brain serotonin (5HT) neurons resulting in decreased food intake and altered autonomic outflow which, in turn, increases metabolism. CRF decreases food intake and, in addition, has been demonstrated to reduce body weight in genetically obese rats through selective activation of sympathetic and inhibition of parasympathetic outflows. Because 5HT is a potent CRF secretagogue, we tested the hypothesis that the weight-reducing effects of fenfluramine administration may be mediated, in part, through altered CRF secretion. Chronic fenfluramine treatment (1-24 mg/kg sc, twice daily, 4 days) resulted in a dose-dependent decrease in hypothalamic CRF concentration at 30 min after the final drug injection and was accompanied by a significant reciprocal increase in plasma corticosterone concentration. These data suggest that the decrease in hypothalamic CRF was a consequence of increased CRF secretion. These changes in hypothalamic CRF and plasma corticosterone correlated with brain fenfluramine levels. In contrast, high dose fenfluramine treatment significantly increased hippocampus, midbrain, and spinal cord CRF concentrations whereas levels in cerebral cortex, caudate putamen, thalamus, pons/medulla, and cerebellum were unaffected. There was no effect of this fenfluramine treatment protocol on regional brain TRH or neurotensin concentrations. In keeping with the well known development of tolerance to the weight-reducing effects of fenfluramine, chronic fenfluramine treatment resulted in lesser increases in corticosterone secretion than after acute treatment. Whereas weight loss observed after chronic fenfluramine treatment was associated with stimulation of hypothalamic-pituitary-adrenocortical hormone secretion, the weight-recovery phase after cessation of drug treatment was associated with decreased levels of plasma corticosterone. These data, demonstrating fenfluramine-induced alterations in brain CRF and plasma corticosterone, suggest that CRF may represent an important endogenous transmitter which mediates the weight-reducing effects of the drug. C1 DUKE UNIV,MED CTR,DEPT PSYCHIAT,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT PHARMACOL,DURHAM,NC 27710. US FDA,DIV NEUROPHARMACOL DRUG PROD,ROCKVILLE,MD 20857. RP APPEL, NM (reprint author), NIDA,ADDICT RES CTR,NEUROBIOL LAB,BLDG 10,ROOM 6C-103,BETHESDA,MD 20892, USA. RI Owens, Michael/G-5191-2012 FU NIMH NIH HHS [MH-39415, MH-42088] NR 59 TC 40 Z9 41 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1991 VL 128 IS 6 BP 3237 EP 3246 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FN112 UT WOS:A1991FN11200073 PM 1645265 ER PT J AU WITT, DM INSEL, TR AF WITT, DM INSEL, TR TI A SELECTIVE OXYTOCIN ANTAGONIST ATTENUATES PROGESTERONE FACILITATION OF FEMALE SEXUAL-BEHAVIOR SO ENDOCRINOLOGY LA English DT Article ID MATERNAL-BEHAVIOR; PROCEPTIVE BEHAVIOR; LORDOSIS BEHAVIOR; BINDING-SITES; RAT-BRAIN; NUCLEUS; RECEPTORS; ESTROGEN; LOCALIZATION; HYPOTHALAMUS AB Although previous studies have demonstrated that exogenous administration of oxytocin (OT) enhances sexual receptivity in female rats, there is no compelling evidence that endogenous OT has a physiological role in the regulation of female sexual behavior. In the current studies we centrally administered d(CH2)5[Tyr(Me)2Thr4,Tyr-NH2(9)]ornithine vasotocin (or OTA), a selective OT receptor antagonist, to block endogenous OT in ovariectomized females primed with different levels of gonadal steroids. After OTA administration (100-1000 ng), females primed with estradiol benzoate (EB; 1-mu-g) and progesterone (P; 250-mu-g) showed reductions in both receptive and proceptive behaviors. These effects of OTA were also evident, though less striking, in females primed with higher doses of EB (10-mu-g) and P (250-mu-g), but significant OTA effects were absent in females primed with EB (10-mu-g) alone. Thus, OTA appeared to attenuate P's facilitation of sexual behavior. Surprisingly, these behavioral effects of OTA administration were not apparent immediately, but emerged only when OTA was given with P 4-6 h before behavioral testing. To determine if these delayed, but lasting, behavioral effects were associated with OTA occupancy of the OT receptor, we measured OT receptor binding ex vivo using receptor autoradiography. Six hours after intracerebroventricular administration of OTA (1000 ng), OT receptor binding was reduced at least 75% in the ventromedial nucleus of the hypothalamus relative to control levels of binding. Thus, those OT receptors previously implicated in the regulation of sexual receptivity appear to be significantly blocked throughout the period of OTA's behavioral effects. Together, these studies lend support to the hypothesis that endogenous OT has a physiological role in the regulation of female sexual behavior. RP WITT, DM (reprint author), NIMH,CLIN SCI LAB,POB 289,POOLESVILLE,MD 20837, USA. NR 32 TC 100 Z9 100 U1 0 U2 3 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1991 VL 128 IS 6 BP 3269 EP 3276 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FN112 UT WOS:A1991FN11200077 PM 1645266 ER PT J AU YUSPA, SH KILKENNY, A CHENG, C ROOP, D HENNINGS, H KRUSZEWSKI, F LEE, E STRICKLAND, J GREENHALGH, DA AF YUSPA, SH KILKENNY, A CHENG, C ROOP, D HENNINGS, H KRUSZEWSKI, F LEE, E STRICKLAND, J GREENHALGH, DA TI ALTERATIONS IN EPIDERMAL BIOCHEMISTRY AS A CONSEQUENCE OF STAGE-SPECIFIC GENETIC CHANGES IN SKIN CARCINOGENESIS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID PROTEIN-KINASE-C; MOUSE SKIN; TERMINAL DIFFERENTIATION; CELL-LINES; PHOSPHOLIPID-METABOLISM; MALIGNANT PROGRESSION; MONOCLONAL-ANTIBODIES; TUMOR PROMOTERS; BENIGN-TUMORS; FOS ONCOGENE AB The induction of cancer on mouse skin by initiation-promotion protocols occurs through stages in which a benign squamous papilloma is an obligate precursor of squamous cell carcinoma. Activation of the Ha-ras gene is sufficient to produce the papilloma phenotype, while additional genetic changes are required for malignant conversion. The introduction of Ha-ras into normal keratinocytes suppresses the expression of differentiation markers, keratin K1 and K10, and loricrin (a cornified envelope precursor) and, to a lesser extent, filaggrin, at the level of transcription. However, cells initiated by Ha-ras express a nonepidermal keratin, K8. The transcription of KS in these cells is sensitive to the level of medium Ca2+ being abundant in 0.5 mM Ca2+ and not detected in 0.05 mM Ca2+. Epidermal differentiation is regulated by signalling, which involves changes in phosphatidylinositol turnover and intracellular Ca2+. Cells initiated by Ha-ras do not differ from normal keratinocytes in their intracellular Ca2+ response patterns, at least in response to changes in extracellular Ca2+ and serum factors. However, c-Ha-ra keratinocytes have a high basal level of phosphatidylinositol (PI) turnover, which is additive with several other inducers of this pathway, including Ca2+ and aluminum fluoride. Additional studies suggest that high turnover of the PI pathway is incompatible with differentiation-specific gene expression in keratinocytes. We suggest this negative relationship is mediated through elevated diacylglycerol production and chronic down-modulation of protein kinase C. Protein kinase C is known to be essential for expression of differentiation-related genes in keratinocytes. Several approaches have been taken to evaluate genes involved in malignant conversion. Stable papilloma cell lines, which express a codon 61 A to T transversion mutation in the Ha-ras gene, were used as recipients of exogenous cloned oncogenes. The EIA and myc genes did not alter the tumor phenotype when transfected cells were tested in vivo. In contrast, two transforming constructs of v-fos caused malignant conversion, while c-fos was ineffective in this regard. He-ras and v-fos were also introduced into normal keratinocytes using defective retroviruses and the recipient cells tested in vivo for tissue phenotype. Co-infected cells produced carcinomas, v-Ha-ras alone produced papillomas, and v-fos alone produced normal skin. The capacity of transforming fos constructs to cause malignant progression in benign cells with a Ha-ras mutation suggests an indirect mechanism through activation of transcription of cellular genes. Among the fos-regulated gene family are secreted proteases, and several of these enzymes are elevated in tumors converted by the combined action of fos and ras oncogenes. These results suggest the possibility that activation of the protease cascade could occur early in malignant progression. The disruptive consequences of active protease secretion on extracellular regulatory processes could account for the disordered expression of keratinocyte-specific genes in carcinomas. RP YUSPA, SH (reprint author), NCI,DIV CANC ETIOL,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892, USA. NR 61 TC 18 Z9 18 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 1991 VL 93 BP 3 EP 10 DI 10.2307/3431160 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA GC052 UT WOS:A1991GC05200001 PM 1773799 ER PT J AU WISEMAN, RW MONTGOMERY, JC HOSOI, J HOU, EW COCHRAN, CJ LAMB, PW BARRETT, JC AF WISEMAN, RW MONTGOMERY, JC HOSOI, J HOU, EW COCHRAN, CJ LAMB, PW BARRETT, JC TI IDENTIFICATION OF GENES ASSOCIATED WITH TUMOR SUPPRESSION IN SYRIAN-HAMSTER EMBRYO CELLS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID NEOPLASTIC TRANSFORMATION; H19 GENE; EXPRESSION; RETINOBLASTOMA; TROPOMYOSIN; ONCOGENES; CANCER; CDNA; ANTIONCOGENES; MUTATIONS AB Loss of a tumor-suppressor gene function appears to play a critical role in the multistep process of neoplastic transformation of Syrian hamster embryo (SHE) cells in vitro. Clonal variants of two independent, preneoplastic cell lines have been isolated that have either retained (termed supB+) or lost (termed supB-) the ability to suppress the tumorigenicity of a highly malignant benzo[a]pyrene-transformed SHE cell line (BP6T) in cell hybrids. We have pursued several approaches in an attempt to identify genes that are responsible for tumor suppression in these cells. The only consistent differences detected in two-dimensional gel analyses of supB+ and supB- cellular proteins were decreases in the levels of two high molecular weight isoforms of tropomyosin in supB- cells. Differential screening of a supB+ cDNA library for genes that are preferentially expressed in supB+ cells yielded cDNA clones for four genes, i.e., collagen type 11, collagen type IX, H19, and a previously unidentified gene (clone 5). Nuclear run-on assays suggested that higher transcription rates were responsible for the increased steady-state levels of some of these transcripts in supB+ cells. DNA sequence comparisons showed that two copies of a 9 bp element, previously identified in each of the mouse H19 enhancers, were also present in the 5' flanking region of the rat type 11 collagen gene. A transcription factor that controls expression of the collagen and H19 genes through binding to this conserved motif would be an attractive candidate for the supB+ gene or at least a mediator of the supB+ phenotype. RP WISEMAN, RW (reprint author), NIEHS,MOLEC CARCINOGENESIS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 45 TC 19 Z9 19 U1 0 U2 1 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 1991 VL 93 BP 105 EP 109 DI 10.2307/3431177 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA GC052 UT WOS:A1991GC05200018 PM 1773782 ER PT J AU BERNSTEIN, LR BENARI, ET SIMEK, SL COLBURN, NH AF BERNSTEIN, LR BENARI, ET SIMEK, SL COLBURN, NH TI GENE-REGULATION AND GENETIC SUSCEPTIBILITY TO NEOPLASTIC TRANSFORMATION - AP-1 AND P80 EXPRESSION IN JB6 CELLS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID PROTEIN KINASE-C; MOUSE EPIDERMAL-CELLS; TRANSCRIPTION FACTOR AP-1; PROMOTER-RESISTANT CELLS; SWISS 3T3 CELLS; PHORBOL ESTERS; ANCHORAGE INDEPENDENCE; PROCOLLAGEN SYNTHESIS; TUMOR PROMOTERS; AUTO-REGULATION AB The mouse epidermal JB6 cell system consists of clonal genetic variants that are sensitive (P+) or resistant (P-) to the promotion of neoplastic transformation by phorbol esters and other tumor-promoting agents. P+ cells display AP-1-dependent phorbol-ester-inducible transactivation of gene expression, whereas P- cells have a defect in transactivation. Transfection of promotion sensitivity gene pro-1 into P- cells reconstituted both P+ phenotype and AP-1-dependent phorbol-ester-inducible transactivation. P- and P+ cells exhibited induction of c-jun and c-fos messenger RNA levels by phorbol ester, but P- cells had significantly lower basal and induced levels of jun mRNA than P+ cells. Basal and induced levels of c-jun protein were significantly lower in P- cells as well. Differences in levels the 80-kDa pI 4.5 protein p80 were also observed in JB6 cells as a function of preneoplastic progression; high levels of p80 protein and mRNA were observed in P- cells, intermediate levels in P+ cells, and negligible levels were observed in transformed derivatives of JB6 cells. Phorbol ester treatment induced phosphorylation but not synthesis of p80. These data are consistent with the hypotheses that AP-1 is required in the signal transduction pathway for promotion of neoplastic transformation by tumor promoter, that pro genes may control AP-1 activity, that threshold levels of Jun mRNA and protein may play a role in transactivation and promotion sensitivity, and that the p80 protein in JB6 cells may behave in vivo as a suppressor of cellular transformation. RP BERNSTEIN, LR (reprint author), NCI,FREDERICK CANC RES FACIL,VIRAL CARCINOGENESIS LAB,CELL BIOL SECT,FREDERICK,MD 21702, USA. NR 62 TC 22 Z9 22 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 1991 VL 93 BP 111 EP 119 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA GC052 UT WOS:A1991GC05200019 PM 1773784 ER PT J AU LEHMAN, TA REDDEL, R PFEIFER, AMA SPILLARE, E KAIGHN, ME WESTON, A GERWIN, BI HARRIS, CC AF LEHMAN, TA REDDEL, R PFEIFER, AMA SPILLARE, E KAIGHN, ME WESTON, A GERWIN, BI HARRIS, CC TI ONCOGENES AND TUMOR-SUPPRESSOR GENES SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID CELL LUNG-CANCER; RETINOBLASTOMA SUSCEPTIBILITY GENE; BRONCHIAL EPITHELIAL-CELLS; K-RAS ONCOGENE; NORMAL HUMAN CHROMOSOME-11; NEOPLASTIC TRANSFORMATION; WILMS TUMOR; T-ANTIGEN; CARCINOMA-CELLS; OSTEO-SARCOMA AB The functional role of oncogenes in human lung carcinogenesis has been investigated by transfer of activated oncogenes into normal cells or an immortalized bronchial epithelial cell line, BEAS-2B. Transfection of v-Ha-ras, Ki-ras, or the combination of myc and raf into BEAS-2B cells produced tumorigenic cell lines, while transfection of raf or myc alone produced nontumorigenic cell lines. In addition to studying the pathogenic role of oncogenes, we are attempting to define negative growth-regulating genes that have tumor-suppressive effects for human lung carcinomas. Our strategy to identify tumor-suppressor genes involves loss of heterozygosity studies, monochromosome-cell fusion, and cell-cell fusion studies. Loss of heterozygosity studies have revealed consistent allelic DNA sequence deletions on chromosome 17p in squamous cell carcinomas, while large cell carcinomas and adenocarcinomas retained this locus. Mutations in p53, a tumor-suppressor gene located on chromosome 17p, have been observed. Cell-cell hybrid clones produced from fusion of nontumorigenic BEAS-2B cells with tumorigenic HuT292DM cells generally are nontumorigenic. The mechanistic role of the known tumor-suppressor genes Rb-1 and p53 in the development of human lung carcinomas is being investigated in this epithelial cell model of human bronchogenic carcinogenesis. C1 NCI,HUMAN CARCINOGENESIS LAB,BLDG 37,ROOM 2C01,BETHESDA,MD 20892. RI Reddel, Roger/A-6635-2014 OI Reddel, Roger/0000-0002-6302-6107 NR 115 TC 13 Z9 13 U1 0 U2 1 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 1991 VL 93 BP 133 EP 144 DI 10.2307/3431181 PG 12 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA GC052 UT WOS:A1991GC05200022 PM 1685442 ER PT J AU REYNOLDS, SH ANDERSON, MW AF REYNOLDS, SH ANDERSON, MW TI ACTIVATION OF PROTOONCOGENES IN HUMAN AND MOUSE LUNG-TUMORS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID K-RAS PROTOONCOGENE; ADENOCARCINOMA; MUTATIONS; SMOKING; CANCER; RATS AB Lung cancer is a leading cause of cancer-related deaths in several nations. Epidemiological studies have indicated that 85% of all lung cancer deaths and 30% of all cancer deaths in the U.S. are associated with tobacco smoking. Various chemicals in tobacco smoke are thought to react with DNA and to ultimately yield heritable mutations. In an effort to understand the molecular mechanisms involved in lung tumorigenesis, we have analyzed proto-oncogene activation in a series of human lung tumors from smokers and spontaneously occurring and chemically induced lung tumors in mice. Approximately 86% of the human lung tumors and > 90% of the mouse lung tumors were found to contain activated oncogenes. ras Oncogenes activated by point mutations were detected in many of the human lung adenocarcinomas and virtually all of the mouse lung adenomas and adenocarcinomas. The mutation profiles of the activated K-ras genes detected in the chemically induced mouse lung tumors suggest that the observed mutations result from genotoxic effects of the chemicals. Comparison of the K-ras mutations observed in the human lung adenocarcinomas with mutation profiles observed in the mouse lung tumors suggest that bulky hydrophobic DNA adducts may be responsible for the majority of the mutations observed in the activated, human K-ras genes. Other data indicate that approximately 20% of human lung tumors contain potentially novel transforming genes that may also be targets for mutagens in cigarette smoke. RP REYNOLDS, SH (reprint author), NIEHS,MOLEC TOXICOL LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 24 TC 16 Z9 16 U1 1 U2 1 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 1991 VL 93 BP 145 EP 148 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA GC052 UT WOS:A1991GC05200023 PM 1773785 ER PT J AU PATTON, SE GUPTA, RP NISHIO, S EDDY, EM JETTEN, AM PLOPPER, CG NETTESHEIM, P HOOK, GER AF PATTON, SE GUPTA, RP NISHIO, S EDDY, EM JETTEN, AM PLOPPER, CG NETTESHEIM, P HOOK, GER TI ULTRASTRUCTURAL IMMUNOHISTOCHEMICAL LOCALIZATION OF CLARA CELL SECRETORY PROTEIN IN PULMONARY EPITHELIUM OF RABBITS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID LUNG SURFACTANT; GLYCOPROTEIN-A; HUMAN AIRWAYS; RAT LUNG; IDENTIFICATION; UTEROGLOBIN; PRODUCTS AB Highly purified Clara cells (93 +/- 3%) isolated from the lungs of rabbits were used to produce an antiserum against Clara cell secretory proteins. This antiserum was used to identify and study the biosynthesis and secretion of [S-35]methionine-labeled proteins from isolated Clara cells. The antiserum recognized one major secretory protein with apparent molecular weight of 6 kDa and reacted weakly with a higher molecular weight protein of about 180 kDa. Biosynthesis and secretion of these proteins was not detected in preparations of isolated alveolar type II cells or alveolar macrophages. Immunocytochemical localization of the antigen with colloidal gold indicated a dual localization in bronchiolar Clara cells. Gold labeling was found over the osmiophilic secretory granules of Clara cells and smooth endoplasmic reticulum. In tracheal Clara cells, labeling was found mostly in association with secretory granules and relatively little in association with the smooth endoplasmic reticulum. Labeling was also found over the lamellar bodies of type II cells, although the reaction was weak. Labeling of ciliated cells, alveolar type I cells, capillary endothelial cells, and alveolar macrophages was not distinguishable from background. These data indicate that Clara cells of both the bronchioles and trachea of rabbits synthesize and secrete the low molecular weight protein previously called Clara cell secretory protein (CCSP). This antigen does not belong to that group of surfactant proteins whose molecular weights range from 26 to 40 kDa. C1 NIEHS,PULM PATHOBIOL LAB,POB 12233,RES TRIANGLE PK,NC 27709. UNIV CALIF DAVIS,SCH VET MED,DEPT ANAT,DAVIS,CA 95616. OI Jetten, Anton/0000-0003-0954-4445 NR 28 TC 20 Z9 20 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 1991 VL 93 BP 225 EP 232 DI 10.2307/3431193 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA GC052 UT WOS:A1991GC05200034 PM 1773794 ER PT J AU HUFF, J CIRVELLO, J HASEMAN, J BUCHER, J AF HUFF, J CIRVELLO, J HASEMAN, J BUCHER, J TI CHEMICALS ASSOCIATED WITH SITE-SPECIFIC NEOPLASIA IN 1394 LONG-TERM CARCINOGENESIS EXPERIMENTS IN LABORATORY RODENTS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID NATIONAL TOXICOLOGY PROGRAM; F344/N RATS; TOXICITY; REFINEMENT; CANCER; MICE AB The carcinogenicity data base used for this paper originated in the late 1960s by the National Cancer Institute and since 1978 has been continued and made more comprehensive by the National Toxicology Program. The extensive files contain among other sets of information detailed pathology data on more than 400 long-term (most often 24 month) chemical carcinogenesis studies, comprised of nearly 1600 individual experiments having at least 10 million tissue sections that have been evaluated for toxicity and carcinogenicity. Using the current data set of 379 studies made up of 1394 experiments, we have compiled listings of chemicals having like carcinogenic target sites for each of the 34 organs or systems for which histopathology diagnoses have been recorded routinely. The most common tumor site is the liver (15% of all experiments), followed in rank order by: lung, hematopoietic system and kidneys, mammary glands, forestomach, thyroid glands, Zymbal glands, urinary bladder, skin and uterus/cervix, and circulatory system and adrenal glands. These compilations are most useful for maintaining a historic perspective when evaluating the carcinogenicity of contemporary experiments. Equally important, the chemical-tumor-organ connection permits an evaluation of how well chemically induced cancers in a particular organ in one sex or species will predict or correlate with the other sex or species. Using liver cancers as an example, the overall interspecies concordance is 80%. Likewise target site predictions can be made for chemicals selected for study that may be similar to those already evaluated; thereby experimental protocols could be adjusted to allow, for example, more extensive pathology on preselected target organs (i.e., serial sections of the kidney). Further from these observations, one could decide to use two strains of mice to evaluate a short-chain chlorinated aliphatic compound or to study a human carcinogen in a sex-species known to develop chemically induced tumors in the same site observed in humans. Structural classes of chemicals having a propensity for certain organs can be easily identified from these data. Sex-species responders to particular induced cancers become clearly evident, such as in the ovary of female mice or in the kidney of male rats. RP HUFF, J (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 59 TC 124 Z9 125 U1 0 U2 1 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 1991 VL 93 BP 247 EP 270 DI 10.2307/3431195 PG 24 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA GC052 UT WOS:A1991GC05200036 PM 1773796 ER PT J AU WAALKES, MP REHM, S SASS, B KONISHI, N WARD, JM AF WAALKES, MP REHM, S SASS, B KONISHI, N WARD, JM TI CHRONIC CARCINOGENIC AND TOXIC EFFECTS OF A SINGLE SUBCUTANEOUS DOSE OF CADMIUM IN THE MALE FISCHER RAT SO ENVIRONMENTAL RESEARCH LA English DT Article ID WISTAR CRL-(WI)BR RATS; RESPONSE ANALYSIS; TUMOR-INDUCTION; INJECTION SITE; INBRED MICE; CANCER; TESTES; METALLOTHIONEIN; PROSTATE; CHLORIDE C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC ETIOL,COMPARAT CARCINOGENESIS LAB,TUMOR PATHOL SECT,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC ETIOL,COMPARAT CARCINOGENESIS LAB,PATHOGENESIS SECT,FREDERICK,MD 21702. RP WAALKES, MP (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC ETIOL,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 43 TC 17 Z9 17 U1 2 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD JUN PY 1991 VL 55 IS 1 BP 40 EP 50 DI 10.1016/S0013-9351(05)80139-2 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA FY231 UT WOS:A1991FY23100004 PM 1855489 ER PT J AU CLERICI, M TACKET, CO VIA, CS LUCEY, DR MULUK, SC ZAJAC, RA BOSWELL, RN BERZOFSKY, JA SHEARER, GM AF CLERICI, M TACKET, CO VIA, CS LUCEY, DR MULUK, SC ZAJAC, RA BOSWELL, RN BERZOFSKY, JA SHEARER, GM TI IMMUNIZATION WITH SUBUNIT HUMAN-IMMUNODEFICIENCY-VIRUS VACCINE GENERATES STRONGER T-HELPER CELL-IMMUNITY THAN NATURAL INFECTION SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTIGENIC SITES; HIV; RECOGNITION; LYMPHOCYTES; INDIVIDUALS; INDUCTION; SEQUENCE; PEPTIDES AB Healthy, human immunodeficiency virus seronegative (HIV-) volunteers were multiply immunized with a recombinant gp 160 (rgp160) candidate acquired immunodeficiency syndrome (AIDS) vaccine. Peripheral blood lymphocytes from volunteers immunized with 40-mu-g or with 80-mu-g (two volunteers per group) of rgp160, as well as from control donors, were tested for T helper (T(h)) cell function either prior to immunization, 8 to 12 months after the third immunization, or 2 to 5 months after the fourth immunization. The T(h) cell functional tests included antigen-induced in vitro interleukin 2 (IL2) production and proliferation in response to influenza A virus (FLU) and to four synthetic peptides of HIV gp120 and gp160, previously demonstrated to be recognized by T cells from HIV naturally infected patients. Our results demonstrate the following: (a) immunization of HIV- individuals with rgp160 results in IL2 production and T cell proliferation in response to HIV determinants; (b) boosting with rgp160 enhances T(h) function; (c) HIV-specific T(h) function is up to 100-fold greater in the multiply immunized volunteers than that observed in asymptomatic, HIV-infected individuals; and (d) multiple immunization with rgp160 does not impair T(h) function to a non-HIV antigen such as influenza A virus. These results indicate that immunization of uninfected individuals with an HIV subunit vaccine results in much stronger T(h) cell immunity than does natural infection and suggests that vaccination against HIV may be possible. C1 NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B17,BETHESDA,MD 20892. WILFORD HALL USAF MED CTR,HIV UNIT,LACKLAND AFB,TX 78236. UNIV MARYLAND,SCH MED,CTR VACCINE DEV,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DIV RHEUMATOL & CLIN IMMUNOL,BALTIMORE,MD 21201. NCI,METAB BRANCH,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,DEPT MED,BALTIMORE,MD 21201. NR 24 TC 45 Z9 45 U1 0 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUN PY 1991 VL 21 IS 6 BP 1345 EP 1349 DI 10.1002/eji.1830210603 PG 5 WC Immunology SC Immunology GA FT005 UT WOS:A1991FT00500002 PM 1845391 ER PT J AU TAKASHI, T GAUSE, WC WILKINSON, M MACLEOD, CL STEINBERG, AD AF TAKASHI, T GAUSE, WC WILKINSON, M MACLEOD, CL STEINBERG, AD TI INTERLEUKIN 1-INDUCED MATURATION OF PROGENITOR THYMOCYTES SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL ANTIGEN RECEPTOR; GENE-EXPRESSION; GENOMIC ORGANIZATION; MOLECULAR-CLONING; MESSENGER-RNA; ALPHA; COMPLEX; ACTIVATION; MOUSE; CHAIN AB Regulation of thymocyte development was assesed by culturing purified CD4-CD8- thymocytes with cytokines. Sorted CD3-CD4-CD8- adult thymocytes responded to the combination of interleukin (IL) 1 plus IL2 without additional mitogens or co-mitogens with both cellular proliferation and cell surface expression of the T cell receptor (TcR)/CD3 complex. IL 2 alone induced neither proliferation nor cell surface TcR/CD3 expression. IL 1 alone was sufficient to induce cell surface TcR/CD3 without proliferation. Prior to stimulation with cytokines, the progenitor CD4-CD8- thymocytes accumulated TcR-beta and CD3-gamma, delta, epsilon and zeta-mRNA but TcR-alpha-mRNA was not detectable. Stimulation with IL 1 led to a dramatic induction of TcR-alpha-mRNA without an increase in the other transcripts. These studies suggest that IL 1 regulates the differentiation status of immature adult thymocytes. Nuclear run-on studies suggested that the increase in TcR-alpha-mRNA accumulation induced by cytokines might result from post-transcriptional accumulation. C1 NIAMS,ARB,CELLULAR IMMUNOL SECT,BLDG 10,ROOM 9N-218,BETHESDA,MD 20892. UNIV CALIF SAN DIEGO,CTR CANC,LA JOLLA,CA 92093. OREGON HLTH SCI UNIV,DEPT MICROBIOL & IMMUNOL,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,VOLLUM INST,PORTLAND,OR 97201. NR 39 TC 5 Z9 5 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUN PY 1991 VL 21 IS 6 BP 1385 EP 1390 DI 10.1002/eji.1830210609 PG 6 WC Immunology SC Immunology GA FT005 UT WOS:A1991FT00500008 PM 1828425 ER PT J AU REISS, D OLIVERI, ME AF REISS, D OLIVERI, ME TI THE FAMILYS CONCEPTION OF ACCOUNTABILITY AND COMPETENCE - A NEW APPROACH TO THE CONCEPTUALIZATION AND ASSESSMENT OF FAMILY STRESS SO FAMILY PROCESS LA English DT Article C1 NIMH,PERSONALITY & SOCIAL PROC RES BRANCH,BETHESDA,MD 20892. RP REISS, D (reprint author), GEORGE WASHINGTON UNIV,MED CTR,DEPT PSYCHIAT & BEHAV SCI,DIV RES,ROSS 613,2300 EYE ST NW,WASHINGTON,DC 20037, USA. FU NIMH NIH HHS [R01-MH26711] NR 30 TC 13 Z9 13 U1 0 U2 0 PU FAMILY PROCESS INC PI VERNON PA PO BOX 460, VERNON, NJ 07462 SN 0014-7370 J9 FAM PROCESS JI Fam. Process PD JUN PY 1991 VL 30 IS 2 BP 193 EP 214 DI 10.1111/j.1545-5300.1991.00193.x PG 22 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA FT283 UT WOS:A1991FT28300004 PM 1860484 ER PT J AU RUSCONI, L DECASTIGLIONE, R GOZZINI, L CIOMEI, M MOLINARI, I BASILICO, L RUBINO, T VINAYEK, R GARDNER, JD AF RUSCONI, L DECASTIGLIONE, R GOZZINI, L CIOMEI, M MOLINARI, I BASILICO, L RUBINO, T VINAYEK, R GARDNER, JD TI BOMBESIN RECEPTOR ANTAGONISTS .2. ANALOGS BASED ON SUBSTANCE-P ANTAGONISTS SO FARMACO LA English DT Article ID SWISS 3T3 CELLS; GASTRIN-RELEASING PEPTIDE; LUNG-CANCER; GROWTH; STIMULATION; VASOPRESSIN; INVITRO; MURINE AB Although bombesin (BN) and substance P share only the C-terminal dipeptide amide, some substance P receptor antagonists are also weak bombesin receptor antagonists. In order to increase the selectivity of the antagonism for the BN receptor, a series of hybrid peptides were synthesized by the solid-phase methodology, and screened on 3T3 fibroblasts for binding and mitogenic activity. The analogues inhibiting BN-induced thymidine incorporation were further tested for peripheral (amylase release and urinary bladder contraction) and central activity (grooming behaviour). C1 FARMITALIA CARLO ERBA SRL,ERBAMONT GRP,VIA DEI GRACCHI 35,I-20146 MILAN,ITALY. FAC SCI MILAN,IST FARMACOL,I-20129 MILAN,ITALY. NIH,DIGEST DIS BRANCH,BETHESDA,MD 20892. NR 30 TC 5 Z9 5 U1 0 U2 0 PU SOC CHIMICA ITALIANA PI ROME PA VIALE LIEGI 48, I-00198 ROME, ITALY SN 0014-827X J9 FARMACO JI Farmaco PD JUN PY 1991 VL 46 IS 6 BP 725 EP 742 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GB046 UT WOS:A1991GB04600001 PM 1722978 ER PT J AU SHIMIZU, Y SHAW, S AF SHIMIZU, Y SHAW, S TI LYMPHOCYTE INTERACTIONS WITH EXTRACELLULAR-MATRIX SO FASEB JOURNAL LA English DT Review DE LYMPHOCYTE; EXTRACELLULAR MATRIX; INTEGRIN; MIGRATION ID T-CELL ACTIVATION; CHICKEN GIZZARD 5'-NUCLEOTIDASE; FIBRONECTIN RECEPTOR COMPLEX; ADHESION MOLECULES; FUNCTIONAL INVOLVEMENT; MONOCLONAL-ANTIBODIES; COLLAGEN RECEPTOR; INTEGRIN FAMILY; LAMININ; RECOGNITION AB To mediate an immune response, lymphocytes must be able to interact with and respond to the surrounding extracellular environment. In addition to cell surface molecules that facilitate adhesion of lymphocytes to other cells, recent studies have demonstrated that lymphocytes interact with glycoproteins and glycosaminoglycans that are major components of the extracellular matrix (ECM). Although many receptors mediating the effects of ECM components on lymphocyte function remain poorly defined, a number of lymphocyte ECM receptors have recently been identified; these include members of the integrin family of adhesion molecules as receptors have recently been identified; these include members of the integrin family of adhesion molecules as well as structurally unrelated molecules such as CD44 and CD26. Furthermore, as lymphocytes must be able to move and analyze various modes of regulation of cell-ECM interactions. As with other cell types, the ECM has been shown to have multiple effect of lymphocytes; functional analysis reveals effects of the ECM on lymphocyte migration, recognition/activation, and differentiation. These studies emphasize: 1) the importance of lymphocytes as a model system for identifying and analyzing ECM receptor expression and function, and 2) the multiple roles that the ECM plays in the function of the immune system in vivo. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. OI Shimizu, Yoji/0000-0001-9760-0288 NR 66 TC 349 Z9 349 U1 1 U2 3 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 JUN PY 1991 VL 5 IS 9 BP 2292 EP 2299 PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA FP872 UT WOS:A1991FP87200011 PM 1860621 ER PT J AU NELSON, LM KIMZEY, LM MERRIAM, GR FLEISHER, TA AF NELSON, LM KIMZEY, LM MERRIAM, GR FLEISHER, TA TI INCREASED PERIPHERAL LYMPHOCYTE-T ACTIVATION IN PATIENTS WITH KARYOTYPICALLY NORMAL SPONTANEOUS PREMATURE OVARIAN FAILURE SO FERTILITY AND STERILITY LA English DT Article ID SOLUBLE INTERLEUKIN-2 RECEPTOR; RHEUMATOID-ARTHRITIS; ADDISONS-DISEASE; SERUM LEVELS; CELLS; AUTOANTIBODIES; MENOPAUSE; INVITRO AB Objective: To determine if soluble interleukin 2 (IL-2) receptor measured in serum by an enzyme-linked immunosorbent assay (ELISA) might be useful in managing patients with karyotypically normal spontaneous premature ovarian failure. Design: Prospective, controlled observation. Setting: Tertiary care research institution. Interventions: None. Patients, Participants: Twenty-four patients with karyotypically normal spontaneous premature ovarian failure comprised the study group. Forty-two healthy men and women comprised the normal reference group. Main Outcome Measures: We measured peripheral T lymphocyte human leukocyte antigen locus DR (HLA-DR) expression and IL-2 receptor expression using monoclonal antibodies and flow cytometry. We measured soluble IL-2 receptor levels in serum using an ELISA. Results: Consistent with previous findings, our patients had significantly higher HLA-DR expression on peripheral T lymphocytes (5.3 +/- 0.46) as compared with controls (3.5 +/- 0.34) (mean +/- SEM, P < 0.01). Seven patients also had elevated IL-2 receptor expression on peripheral T lymphocytes (P < 0.05). However, soluble IL-2 receptor levels in the serum did not differ significantly from normals. Conclusions: Patients with karyotypically normal spontaneous premature ovarian failure have a modest increase in peripheral T lymphocyte activation measured by flow cytometry. This degree of activation does not result in increased soluble IL-2 receptor release measured by ELISA. C1 NIH,CLIN CTR,DEPT NURSING,BETHESDA,MD 20892. NIH,CLIN CTR,IMMUNOL SERV,BETHESDA,MD 20892. RP NELSON, LM (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N262,BETHESDA,MD 20892, USA. NR 25 TC 21 Z9 21 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 JUN PY 1991 VL 55 IS 6 BP 1082 EP 1087 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA FQ074 UT WOS:A1991FQ07400010 PM 2037104 ER PT J AU WATSON, JD AF WATSON, JD TI TECHNOLOGY DEVELOPMENT IN KEY AREAS CAN HELP HUMAN GENOME PROJECT REACH ITS GOALS SO GENETIC ENGINEERING NEWS LA English DT Editorial Material C1 NATL CTR HUMAN GENOME RES,BETHESDA,MD. COLD SPRING HARBOR LAB,COLD SPRING HARBOR,NY 11724. NR 0 TC 1 Z9 1 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0270-6377 J9 GENET ENG NEWS JI Genet. Eng. News PD JUN PY 1991 VL 11 IS 6 BP 4 EP & PG 0 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA GA762 UT WOS:A1991GA76200005 ER PT J AU SIRACUSA, LD ROSNER, MH VIGANO, MA GILBERT, DJ STAUDT, LM COPELAND, NG JENKINS, NA AF SIRACUSA, LD ROSNER, MH VIGANO, MA GILBERT, DJ STAUDT, LM COPELAND, NG JENKINS, NA TI CHROMOSOMAL LOCATION OF THE OCTAMER TRANSCRIPTION FACTORS, OTF-1, OTF-2, AND OTF-3, DEFINES MULTIPLE OTF-3-RELATED SEQUENCES DISPERSED IN THE MOUSE GENOME SO GENOMICS LA English DT Article ID TUMOR NECROSIS FACTOR; MAJOR HISTOCOMPATIBILITY COMPLEX; INTERSPECIFIC BACKCROSS ANALYSIS; RETINOIC ACID RECEPTOR; BINDING PROTEIN OCT-1; POU-DOMAIN PROTEIN; HISTONE H2B GENE; HOMEO BOX; CAENORHABDITIS-ELEGANS; LINKAGE MAP C1 NCI,METAB BRANCH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL-BRP,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 70 TC 68 Z9 68 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 JUN PY 1991 VL 10 IS 2 BP 313 EP 326 DI 10.1016/0888-7543(91)90314-5 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA FL240 UT WOS:A1991FL24000003 PM 1676977 ER PT J AU COX, RD COPELAND, NG JENKINS, NA LEHRACH, H AF COX, RD COPELAND, NG JENKINS, NA LEHRACH, H TI INTERSPERSED REPETITIVE ELEMENT POLYMERASE CHAIN-REACTION PRODUCT MAPPING USING A MOUSE INTERSPECIFIC BACKCROSS SO GENOMICS LA English DT Article ID YEAST ARTIFICIAL CHROMOSOMES; GENETIC-LINKAGE MAP; COMPLEX GENOMES; RAPID ISOLATION; GROWTH-FACTOR; HOMEO BOX; DNA; LOCALIZATION; SEQUENCE; CLONING C1 NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RP COX, RD (reprint author), IMPERIAL CANC RES FUND,GENOME ANAL LAB,POB 123,LINCOLNS INN FIELDS,LONDON WC2A 3PX,ENGLAND. FU PHS HHS [N01-C0-74101] NR 41 TC 59 Z9 59 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 JUN PY 1991 VL 10 IS 2 BP 375 EP 384 DI 10.1016/0888-7543(91)90322-6 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA FL240 UT WOS:A1991FL24000011 PM 2071145 ER PT J AU ALEMANY, J SOLER, AP SMITH, RM ROTH, J JARETT, L DEPABLO, F AF ALEMANY, J SOLER, AP SMITH, RM ROTH, J JARETT, L DEPABLO, F TI EMBRYONIC CHICKEN LENS CELLS CULTURED IN RECONSTITUTED BASEMENT-MEMBRANE - AN EXPERIMENTAL-MODEL TO MAINTAIN THE EPITHELIAL PHENOTYPE IN CULTURE SO GROWTH REGULATION LA English DT Note ID GROWTH; EXPRESSION; LAMININ; DIFFERENTIATION; PROTEINS; DOMAINS; GENE AB The action of a reconstituted basement membrane has been studied on primary cultures of embryonic lens cells. When a solution of this matrix (Matrigel) was included in the culture medium, a high percentage of cells maintained the epithelial phenotype, judged by electron microscopy criteria, in contrast to the differentiated state induced by serum. Complete matrix stimulated by 6-fold the incorporation of H-3-thymidine into the cells, while one of its defined components, laminin, only had a 2-fold stimulatory effect. Thus, the basement membrane may stimulate mitogenesis and play a role complementary to that of growth factors in development. C1 NIDDK,DIABET BRANCH,BLDG 10,ROOM 8-S-243,BETHESDA,MD 20892. UNIV PENN,SCH MED,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. RP DEPABLO, F (reprint author), NIDDK,DIABET BRANCH,BLDG 10,ROOM 8-S-243,BETHESDA,MD 20892, USA. FU NIDDK NIH HHS [DK 28143, DK 19525] NR 13 TC 1 Z9 1 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0956-523X J9 GROWTH REGULAT JI Growth Regul. PD JUN PY 1991 VL 1 IS 2 BP 62 EP 64 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GU439 UT WOS:A1991GU43900004 PM 1842562 ER PT J AU BECK, HL BOUVILLE, A AF BECK, HL BOUVILLE, A TI USE OF GUMMED-FILM FALLOUT DATA - REPLY SO HEALTH PHYSICS LA English DT Letter C1 NCI, RADIAT EFFECTS BRANCH, BETHESDA, MD 20892 USA. RP BECK, HL (reprint author), US DOE, ENVIRONM MEASUREMENTS LAB, 376 HUDSON ST, NEW YORK, NY 10014 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD JUN PY 1991 VL 60 IS 6 BP 863 EP 864 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA FN604 UT WOS:A1991FN60400014 ER PT J AU YARBROUGH, J CUNNINGHAM, M YAMANAKA, H THURMAN, R BADR, M AF YARBROUGH, J CUNNINGHAM, M YAMANAKA, H THURMAN, R BADR, M TI CARBOHYDRATE AND OXYGEN-METABOLISM DURING HEPATOCELLULAR PROLIFERATION - A STUDY IN PERFUSED LIVERS FROM MIREX-TREATED RATS SO HEPATOLOGY LA English DT Article ID PARTIAL-HEPATECTOMY; GROWTH; LOBULE AB Liver regeneration after partial hepatectomy is accompanied by altered hepatic intermediary metabolism. Because the organochlorine compound mirex also causes liver cell growth, the purpose of this study was to investigate hepatic carbohydrate and oxygen metabolism in perfused livers from mirex-treated rats and to localize cell proliferation in this model. Pretreatment with mirex (100 mg/kg, intragastrically) increased liver/body weight ratios and DNA synthesis in livers of fed rats, effects that were markedly diminished in livers of fasted rats. This finding shows that liver growth caused by mirex, as is the case after partial hepatectomy, is hindered when animals are deprived of food. Furthermore, perfused livers from mirex-treated rats had depleted glycogen stores but significantly elevated oxygen uptake compared with livers from control rats. Increases in oxygen uptake and hepatocellular proliferation were observed mostly in periportal regions of the liver lobule. In regenerating livers, most DNA synthesis was reported to also occur in these regions of the liver lobule. Taken together, these data show that liver cell growth caused by mirex is accompanied by changes in hepatic intermediary metabolism and sublobular proliferation similar to those observed after partial hepatectomy. C1 UNIV MISSOURI,MED SCH BLDG,2411 HOLMES ST,M3-115,KANSAS CITY,MO 64108. UNIV N CAROLINA,DEPT PHARMACOL,HEPATOBIOL & TOXICOL LAB,CHAPEL HILL,NC 27599. NIEHS,EXPTL TOXICOL BRANCH,RES TRIANGLE PK,NC 27709. FU NIEHS NIH HHS [ES-04778, ES-04771] NR 28 TC 15 Z9 15 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 JUN PY 1991 VL 13 IS 6 BP 1229 EP 1234 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA FT650 UT WOS:A1991FT65000031 PM 2050337 ER PT J AU BURRIS, AS GRACELY, RH CARTER, CS SHERINS, RJ DAVIDSON, JM AF BURRIS, AS GRACELY, RH CARTER, CS SHERINS, RJ DAVIDSON, JM TI TESTOSTERONE THERAPY IS ASSOCIATED WITH REDUCED TACTILE SENSITIVITY IN HUMAN MALES SO HORMONES AND BEHAVIOR LA English DT Article ID SEXUAL-BEHAVIOR; MEN; DYSFUNCTION; PENILE C1 UNIV MARYLAND,DEPT ZOOL,COLLEGE PK,MD 20742. STANFORD UNIV,DEPT CELLULAR & MOLEC PHYSIOL,STANFORD,CA 94305. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NIDR,NEUROBIOL & ANESTHESIOL BRANCH,CLIN PAIN SECT,BETHESDA,MD 20892. NR 17 TC 19 Z9 19 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0018-506X J9 HORM BEHAV JI Horm. Behav. PD JUN PY 1991 VL 25 IS 2 BP 195 EP 205 DI 10.1016/0018-506X(91)90050-R PG 11 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA FP176 UT WOS:A1991FP17600006 PM 2066080 ER PT J AU ANDERSON, WF AF ANDERSON, WF TI STEADY PROGRESS SO HUMAN GENE THERAPY LA English DT Editorial Material RP ANDERSON, WF (reprint author), NHLBI,MOLEC HEMATOL BRANCH,BLDG 10,7D-18,BETHESDA,MD 20892, USA. NR 0 TC 8 Z9 8 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 SUM PY 1991 VL 2 IS 2 BP 99 EP 100 DI 10.1089/hum.1991.2.2-99 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA FY105 UT WOS:A1991FY10500001 ER PT J AU CULVER, KW ANDERSON, WF BLAESE, RM AF CULVER, KW ANDERSON, WF BLAESE, RM TI LYMPHOCYTE GENE-THERAPY SO HUMAN GENE THERAPY LA English DT Article; Proceedings Paper CT CONF ON GENE THERAPY CY APR 24-26, 1991 CL BOSTON, MA ID ADENOSINE-DEAMINASE DEFICIENCY AB Genetically corrected T cells are currently under investigation as a treatment for severe combined immunodeficiency disease resulting from a lack of adenosine deaminase (ADA). Monthly injections of these ADA-corrected T cells have resulted in measurable ADA activity in the peripheral blood and the in vivo production of antibody to blood group antigen. Genetically corrected T cells appear to be clinically valuable vehicles for gene therapy. C1 NIH,METAB BRANCH,BLDG 10,ROOM 6B05,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 13 TC 115 Z9 116 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 SUM PY 1991 VL 2 IS 2 BP 107 EP 109 DI 10.1089/hum.1991.2.2-107 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA FY105 UT WOS:A1991FY10500003 PM 1911929 ER PT J AU FONG, D SMITH, DI HSIEH, WT AF FONG, D SMITH, DI HSIEH, WT TI THE HUMAN KININOGEN GENE (KNG) MAPPED TO CHROMOSOME 3Q26-QTER BY ANALYSIS OF SOMATIC-CELL HYBRIDS USING THE POLYMERASE CHAIN-REACTION SO HUMAN GENETICS LA English DT Article ID CATHEPSIN-B; PROTEINASE-INHIBITOR; MOLECULAR-WEIGHT; MAPPING PANEL; LOCALIZATION; EXPRESSION; EVOLUTION; CST3; CDNA AB Kinins, peptide products of kininogens, may be involved in hypertensive and diabetic diseases, and inflammatory disorders. The human kininogen gene (KNG) has been mapped to chromosome 3, using a panel of human-hamster somatic cell hybrids by polymerase chain reaction of hybrid DNA with gene-specific primers. KNG was further assigned to 3q26-3qter, using DNA from a second panel of chromosome 3 deletion mapping cell hybrids. C1 RUTGERS STATE UNIV, BUR BIOL RES, PISCATAWAY, NJ 08855 USA. WAYNE STATE UNIV, SCH MED, DEPT MOLEC BIOL & GENET, DETROIT, MI 48201 USA. NIMH, CLIN NEUROGENET BRANCH, BETHESDA, MD 20892 USA. RP FONG, D (reprint author), RUTGERS STATE UNIV, DEPT BIOL SCI, C226 NELSON BIOL LABS, PISCATAWAY, NJ 08855 USA. FU NCI NIH HHS [CA48031, CA49359] NR 26 TC 21 Z9 21 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JUN PY 1991 VL 87 IS 2 BP 189 EP 192 DI 10.1007/BF00204179 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA FT647 UT WOS:A1991FT64700018 PM 2066106 ER PT J AU GLENN, GM DANIEL, LN CHOYKE, P LINEHAN, WM OLDFIELD, E GORIN, MB HOSOE, S LATIF, F WEISS, G WALTHER, M LERMAN, MI ZBAR, B AF GLENN, GM DANIEL, LN CHOYKE, P LINEHAN, WM OLDFIELD, E GORIN, MB HOSOE, S LATIF, F WEISS, G WALTHER, M LERMAN, MI ZBAR, B TI VONHIPPEL-LINDAU (VHL) DISEASE - DISTINCT PHENOTYPES SUGGEST MORE THAN ONE MUTANT ALLELE AT THE VHL LOCUS SO HUMAN GENETICS LA English DT Article ID FAMILIAL PHEOCHROMOCYTOMA; MANIFESTATIONS; CARCINOMA; MEMBERS; LINKAGE; REGION AB As part of an attempt to locate the von Hippel-Lindau locus (VHL) on chromosome 3, we evaluated 41 families with von Hippel-Lindau disease from the United States and Canada. One large family was identified whose disease phenotype was distinct from typical VHL. The most common disease manifestation was pheochromocytoma occuring in 57% (27/47) of affected family members. Few (4/47) affected family members had symptomatic spinal or cerebellar hemangioblastomas; no affected family member had renal cell carcinoma (0/47) or pancreatic cysts (0/24). Previously, genetic analysis demonstrated that the disease manifestations in this family were linked to RAF1 and D3S18, markers shown to be linked to typical VHL. These results suggest that there are mutant alleles at the VHL locus associated with distinct tissue specificities. C1 NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,BLDG 560,ROOM 12-71,FREDERICK,MD 21701. NIH,CTR CLIN,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. UNIV PITTSBURGH,SCH MED,EYE & EAR INST PITTSBURGH,DEPT OPHTHALMOL,PITTSBURGH,PA 15261. NR 24 TC 61 Z9 61 U1 0 U2 6 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JUN PY 1991 VL 87 IS 2 BP 207 EP 210 DI 10.1007/BF00204184 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA FT647 UT WOS:A1991FT64700023 PM 2066108 ER PT J AU GROSSMAN, E GOLDSTEIN, DS HOFFMAN, A KEISER, HR AF GROSSMAN, E GOLDSTEIN, DS HOFFMAN, A KEISER, HR TI GLUCAGON AND CLONIDINE TESTING IN THE DIAGNOSIS OF PHEOCHROMOCYTOMA SO HYPERTENSION LA English DT Article DE PHEOCHROMOCYTOMA; GLUCAGON; CLONIDINE; NOREPINEPHRINE; EPINEPHRINE; DIHYDROXYPHENYLGLYCOL ID SUPPRESSION TEST; HYPERTENSIVE PATIENTS; BIOCHEMICAL TESTS; PLASMA-LEVELS; NOREPINEPHRINE; CATECHOLAMINES; RESPONSES; EXCLUSION; RECEPTOR; URINARY AB We assessed the sensitivity and specificity of glucagon stimulation and clonidine suppression tests in the diagnosis of pheochromocytoma in 113 hypertensive patients, 39 with and 74 without the tumor. In the glucagon stimulation test, blood was sampled 2 minutes after intravenous injection of 0.28-mu-mol (1 mg) glucagon, and in the clonidine suppression test, blood was sampled 3 hours after administration of oral clonidine, 1.30-mu-mol (0.3 mg)/70 kg body wt. Baseline levels of catechols in antecubital venous blood were abnormal, with norepinephrine greater than 7.10 nmol/l (1,200 pg/m), epinephrine greater than 1.51 nmol/l (276 pg/ml), norepinephrine/dihydroxyphenylglycol (DHPG) ratio greater than 1.09, or dopa greater than 35.53 nmol/l (7,000 pg/ml), in 30 of 39 patients with pheochromocytoma (sensitivity 77%) and 1 of 74 patients without pheochromocytoma (specificity 99%). Results of the glucagon test were abnormal (norepinephrine greater than 11.83 nmol/l [2,000 pg/ml] or more than threefold increase from baseline) in 25 of 31 patients with pheochromocytoma (sensitivity 81%) and 0 of 72 patients without pheochromocytoma (specificity 100%). Results of the clonidine test were abnormal (after clonidine norepinephrine greater than 2.96 nmol/l [500 pg/ml] or less than 50% decrease from baseline) in 29 of 30 patients with pheochromocytoma (sensitivity 97%) and in 7 of 30 patients without pheochromocytoma (specificity 67%). Very high baseline levels of catechols therefore indicated the presence of pheochromocytoma, but there were several false-negative results when normal levels were obtained. The glucagon test alone was highly specific but not sensitive, and the clonidine test was highly sensitive but less specific. Of 50 patients undergoing both glucagon stimulation and clonidine suppression tests, the results of at least one test were abnormal in 22 of 22 patients with pheochromocytoma (sensitivity 100%) and in 6 of 28 patients without pheochromocytoma (specificity 79%). When both tests were negative, the diagnosis could be excluded, and the results were conclusive in 80% of the patients. Combined glucagon stimulation and clonidine suppression testing is worthwhile in the diagnosis of pheochromocytoma by blood tests. C1 NHLBI,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. NR 30 TC 70 Z9 72 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUN PY 1991 VL 17 IS 6 BP 733 EP 741 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA FR324 UT WOS:A1991FR32400002 PM 2045133 ER PT J AU WINKLER, DF MYERS, KR HOCHSTEIN, HD ULRICH, JT WUNDERLICH, JR AF WINKLER, DF MYERS, KR HOCHSTEIN, HD ULRICH, JT WUNDERLICH, JR TI BACTERIAL LIPOPOLYSACCHARIDE ACTS SYNERGISTICALLY WITH SELECTED MACROMOLECULAR POLYANIONS TO INDUCE MHC-NONRESTRICTED CYTOTOXIC-CELLS SO IMMUNOBIOLOGY LA English DT Article ID ACTIVATED KILLER CELLS; DEXTRAN SULFATE; B-CELLS; LIPID-A; RECOMBINANT INTERLEUKIN-2; POLYCLONAL ACTIVATORS; ESCHERICHIA-COLI; LYMPHOCYTES-B; DNA-SYNTHESIS; LAK CELLS AB We examined whether bacterial lipopolysaccharide, at a dose range extending to less than 1.0 ng/ml, would work with cofactors to induce MHC-nonrestricted cytotoxic cells. To this end, normal mouse splenocytes were cultured for 5 days with LPS and potential cofactors, after which the cells were tested for cytotoxic activity in short-term Cr-51-release assays. We found that LPS can act synergistically with the macromolecular polyanions, dextran sulfate and polyinosinic acid. The effector cells induced by LPS and polyanions showed characteristics of activated NK cells in that they were (1) cytotoxic for widely differing sources of tumor cells, (2) not inhibited by an anti-T cell receptor antibody, and (3) not removed by depletion of CD4+ or CD8+ cells. LPS was active at picogram concentrations when dextran sulfate was included. Exposure of splenocytes to LPS was necessary during the early phase of the 5-day culture, but as little as 1 h of exposure was required, whereas exposure to the macromolecular polyanions during either the first or the last 2 days of a 5-day culture with LPS was effective. As expected with LPS activity, the cytotoxic cell response was prevented by polymyxin B or by the use of splenocytes from LPS non-responder C3H/HeJ mice. Screening of the S. minnesota R mutants and other partial LPS structures revealed that lipid A was closely associated with LPS activity in this assay system and that at least one partially detoxified structure, a deacylated LPS, could substitute for native LPS. C1 RIBI IMMUNOCHEM RES INC,HAMILTON,MT. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20014. RP WINKLER, DF (reprint author), NCI,DCBDC,EXPTL IMMUNOL BRANCH,BLD 10,RM 4B-17,BETHESDA,MD 20892, USA. NR 56 TC 1 Z9 1 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI STUTTGART PA WOLLGRASWEG 49, D-70599 STUTTGART, GERMANY SN 0171-2985 J9 IMMUNOBIOLOGY JI Immunobiology PD JUN PY 1991 VL 182 IS 3-4 BP 216 EP 233 PG 18 WC Immunology SC Immunology GA FP854 UT WOS:A1991FP85400002 PM 1916877 ER PT J AU SCHMITZ, JL SCHELL, RF LOVRICH, SD CALLISTER, SM COE, JE AF SCHMITZ, JL SCHELL, RF LOVRICH, SD CALLISTER, SM COE, JE TI CHARACTERIZATION OF THE PROTECTIVE ANTIBODY-RESPONSE TO BORRELIA-BURGDORFERI IN EXPERIMENTALLY INFECTED LSH HAMSTERS SO INFECTION AND IMMUNITY LA English DT Article ID LYME-DISEASE SPIROCHETE; PASSIVE-IMMUNIZATION; INVITRO CULTIVATION; ARTHRITIS; PROTEINS; MICE; OSPA; HISTOPATHOLOGY; INDUCTION; AGENT AB We show that serum obtained from normal hamsters infected with Borrelia burgdorferi can confer complete protection on irradiated recipients challenged with the Lyme spirochete. Borreliacidal activity was detected 7 days after infection, peaked at weeks 3 to 5, and thereafter decreased. Relatively high borreliacidal activity was detected in immune serum at weeks 3 and 5 of infection. The borreliacidal activity did not correlate with antibody used for the serodiagnosis of Lyme disease, which remained elevated throughout experimental infection. Our results also demonstrated that blocking antibody and antigenic variation in B. burgdorferi did not account for the decreasing titer of protective antibody. These findings indicate that protection against reinfection gradually wanes. C1 WISCONSIN STATE LAB HYG,MADISON,WI 53706. GUNDERSON MED FDN,LA CROSSE,WI 54601. UNIV WISCONSIN,DEPT BACTERIOL,MADISON,WI 53706. UNIV WISCONSIN,DEPT MED MICROBIOL & IMMUNOL,MADISON,WI 53706. NIH,ROCKY MT LABS,HAMILTON,MT 59840. FU NIAID NIH HHS [AI-22199] NR 36 TC 58 Z9 58 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 JUN PY 1991 VL 59 IS 6 BP 1916 EP 1921 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA FN775 UT WOS:A1991FN77500008 PM 2037352 ER PT J AU EKWUNIFE, FS TAYLOR, CE FAUNTLEROY, MB STASHAK, PW BAKER, PJ AF EKWUNIFE, FS TAYLOR, CE FAUNTLEROY, MB STASHAK, PW BAKER, PJ TI DIFFERENTIAL-EFFECTS OF MONOPHOSPHORYL LIPID A ON EXPRESSION OF SUPPRESSOR T-CELL ACTIVITY IN LIPOPOLYSACCHARIDE-RESPONSIVE AND LIPOPOLYSACCHARIDE-DEFECTIVE STRAINS OF C3H MICE SO INFECTION AND IMMUNITY LA English DT Note ID III PNEUMOCOCCAL POLYSACCHARIDE; ANTIBODY-PRODUCING CELLS; ENDOTOXIN; PROLIFERATION; INACTIVATION; LYMPHOCYTES; MAGNITUDE; BINDING; LEVEL AB Lipopolysaccharide (LPS)-responsive and LPS-defective strains of C3H mice did not differ in the capacity to make an antibody response to type III pneumococcal polysaccharide or in the degree of thymus-derived suppressor cell (Ts) activity generated following exposure to type III pneumococcal polysaccharide. However, treatment with monophosphoryl lipid A (MPL) abolished the expression of Ts function in LPS-responsive but not LPS-defective mice. Since this effect was elicited by different preparations of MPL, it appears to be a general property of MPL mediated by direct action of MPL on activated Ts. C1 NIAID,IMMUNOGENET LAB,TWINBROOK II RES FACIL,12441 PARKLAWN DR,ROCKVILLE,MD 20852. UNIV MARYLAND,DEPT NAT SCI,PRINCESS ANNE,MD 21853. NR 21 TC 9 Z9 9 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 JUN PY 1991 VL 59 IS 6 BP 2192 EP 2194 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA FN775 UT WOS:A1991FN77500052 PM 1828058 ER PT J AU KLEIN, HG AF KLEIN, HG TI FUTURE TECHNOLOGIES IN TRANSFUSION MEDICINE SO INFUSIONSTHERAPIE UND TRANSFUSIONSMEDIZIN LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; AUTOLOGOUS BLOOD; THERAPY; IMMUNOTHERAPY RP KLEIN, HG (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892, USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1019-8466 J9 INFUSIONSTHERAPIE JI Infusionsther. Transfusionsmed. PD JUN PY 1991 VL 18 SU 1 BP 31 EP 34 PG 4 WC Hematology; Immunology SC Hematology; Immunology GA FX091 UT WOS:A1991FX09100007 PM 1917063 ER PT J AU BORNSTEIN, MH GAUGHRAN, JM SEGUI, I AF BORNSTEIN, MH GAUGHRAN, JM SEGUI, I TI MULTIMETHOD ASSESSMENT OF INFANT TEMPERAMENT - MOTHER QUESTIONNAIRE AND MOTHER AND OBSERVER REPORTS EVALUATED AND COMPARED AT 5 MONTHS USING THE INFANT TEMPERAMENT MEASURE SO INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT LA English DT Article ID INTRACLASS CORRELATIONS; STABILITY; BEHAVIOR; DIFFICULTNESS; CRITIQUE; TWINS C1 NYU,NEW YORK,NY 10003. CUNY,GRAD CTR,NEW YORK,NY 10021. RP BORNSTEIN, MH (reprint author), NATL INST CHILD HLTH & HUMAN DEV,CHILD & FAMILY RES SECT,BLDG 31,ROOM B2B15,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 64 TC 22 Z9 22 U1 17 U2 18 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0165-0254 J9 INT J BEHAV DEV JI Int. J. Behav. Dev. PD JUN PY 1991 VL 14 IS 2 BP 131 EP 151 PG 21 WC Psychology, Developmental SC Psychology GA FP643 UT WOS:A1991FP64300001 ER PT J AU STEINERT, PM MACK, JW KORGE, BP GAN, SQ HAYNES, SR STEVEN, AC AF STEINERT, PM MACK, JW KORGE, BP GAN, SQ HAYNES, SR STEVEN, AC TI GLYCINE LOOPS IN PROTEINS - THEIR OCCURRENCE IN CERTAIN INTERMEDIATE FILAMENT CHAINS, LORICRINS AND SINGLE-STRANDED RNA-BINDING PROTEINS SO INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES LA English DT Article; Proceedings Paper CT 1990 SATELLITE CONGRESS OF THE INTERNATIONAL UNION OF PURE AND APPL BIOPHYSICS CY AUG 07-10, 1990 CL PALMERSTON NORTH, NEW ZEALAND SP INT UNION PURE & APPL BIOPHYS DE GLYCINE LOOPS; RNA BINDING PROTEINS; KERATIN; LORICRINS; NUCLEAR MAGNETIC RESONANCE ID HELIX-DESTABILIZING PROTEIN; EPIDERMAL KERATIN FILAMENTS; AMINO-ACID-SEQUENCE; SECONDARY STRUCTURE; GLOBULAR-PROTEINS; ASSEMBLED INVITRO; XENOPUS-LAEVIS; CDNA CLONING; II KERATINS; HUMAN GENE AB Quasi-repetitive, glycine-rich peptide sequences are widespread in at least three distinct families of proteins: the keratins and other intermediate filament proteins, including nuclear lamins; loricrins, which are major envelope components of terminally differentiated epithelial cells; and single-stranded RNA binding proteins. We propose that such sequences comprise a new structural motif termed the 'glycine loop'. The defining characteristics of glycine loop sequences are: (1) they have the form x(y)n, where x is usually an aromatic or occasionally a long-chain aliphatic residue; y is usually glycine but may include polar residues such as serine, asparagine, arginine, cysteine, and rarely other residues; and the value of n is highly variable, ranging from 1 to 35 in examples identified to date. (2) Glycine-loop-containing domains are though to form when at least two and to date, as many as 18, such quasi-repeats are configured in tandem, so that the entire domain in a protein may be 50-150 residues long. (3) The average value of n, the pattern of residues found in the x position and the non-glycine substitutions in the y position appear to be characteristic of a given glycine loop containing domain, whereas the actual number of repeats is less constrained. (4) Glycine loop sequences display a high degree of evolutionary sequence variability and even allelic variations among different individuals of the same vertebrate species. (5) Glycine loop sequences are expected to be highly flexible, but possess little other regular secondary structure. It is hypothesized that glycine loop motifs in a given domain may organize into higher-order structures anchored on packing of the x residues, and that multiple interactions between configurations of the neighbouring glycine loops on the same or adjacent different protein molecules may form the basis for adaptable intra-cytoskeletal and envelope-cytoskeletal interactions in the epidermis. In view of the few residues that are involved in glycine loops, their high abundance when they do occur, and the likelihood that individual glycine loops do not have uniquely defined conformation, n.m.r. spectroscopy appears to offer the best prospects to investigate the implications of these proposals. C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. NIAMSD,STRUCT BIOL RES LAB,BETHESDA,MD 20892. RP STEINERT, PM (reprint author), NIAMD,SKIN BIOL LAB,BETHESDA,MD 20892, USA. NR 77 TC 155 Z9 159 U1 0 U2 10 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0141-8130 J9 INT J BIOL MACROMOL JI Int. J. Biol. Macromol. PD JUN PY 1991 VL 13 IS 3 BP 130 EP 139 DI 10.1016/0141-8130(91)90037-U PG 10 WC Biochemistry & Molecular Biology; Chemistry, Applied; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA FT321 UT WOS:A1991FT32100002 PM 1716976 ER PT J AU STEVEN, AC KOCSIS, E UNSER, M TRUS, BL AF STEVEN, AC KOCSIS, E UNSER, M TRUS, BL TI SPATIAL DISORDERS AND COMPUTATIONAL CURES SO INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES LA English DT Article; Proceedings Paper CT 1990 SATELLITE CONGRESS OF THE INTERNATIONAL UNION OF PURE AND APPL BIOPHYSICS CY AUG 07-10, 1990 CL PALMERSTON NORTH, NEW ZEALAND SP INT UNION PURE & APPL BIOPHYS DE DIGITAL IMAGE PROCESSING; BIOLOGICAL ELECTRON MICROSCOPY; SPATIAL DISORDER; PROTEIN CRYSTALS; CURVILINEAR COORDINATES; CORRELATION AVERAGING; MULTIVARIATE STATISTICS ID CRYO-ELECTRON MICROSCOPY; MICROGRAPHS; IMAGES; FILAMENTS; PROTEIN; RESOLUTION; FIELD; RECONSTRUCTION; POLYHEADS; SUBUNITS AB Image averaging provides a powerful method for enhancing the yield of interpretable information from electron micrographs of biological macromolecules. However, as originally conceived, the full benefit of averaging is achieved only with perfectly ordered two-dimensional crystals. More recent developments, reviewed here, allow one to rectify disordered lattices, straighten randomly bent filaments, and combine multiple images of free-standing particles, thus extending the advantages of image averaging to virtually every class of macromolecular specimen. C1 NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,COMP SYST LAB,BETHESDA,MD 20892. RP STEVEN, AC (reprint author), NIAMSD,STRUCT BIOL RES LAB,BETHESDA,MD 20892, USA. RI Unser, Michael/A-1550-2008 NR 40 TC 5 Z9 5 U1 0 U2 1 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0141-8130 J9 INT J BIOL MACROMOL JI Int. J. Biol. Macromol. PD JUN PY 1991 VL 13 IS 3 BP 174 EP 180 DI 10.1016/0141-8130(91)90044-U PG 7 WC Biochemistry & Molecular Biology; Chemistry, Applied; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA FT321 UT WOS:A1991FT32100009 PM 1911559 ER PT J AU DAMIBA, AE KELLEY, KF VERMUND, SH AF DAMIBA, AE KELLEY, KF VERMUND, SH TI RISING TREND OF REPORTED PRIMARY GENITAL SYPHILIS AND GENITAL ULCER DISEASE IN BURKINA-FASO SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article ID SEXUALLY-TRANSMITTED DISEASES; HUMAN IMMUNODEFICIENCY VIRUS; CONGENITAL-SYPHILIS; INFECTION; AFRICA; EPIDEMIOLOGY; PROSTITUTES; GONORRHEA; NAIROBI; LUSAKA AB Recent trends in reported primary genital syphilis and genital ulcer disease (GUD) were assessed in Burkina Faso using incidence data reported to the Ministry of Health. From 1978 to 1983 the yearly reports of genital syphilis and GUD rose by 42%. A single period moving average was calculated for each consecutive 13-week period from 1978 to 1983, documenting an average 7% rise per year. Severe limitations in the Ministry of Health of personnel and other resources for surveillance were noted and no improvements in surveillance methods were evident during this study. The rising trend suggests a growing problem of ulcerative sexually transmitted diseases, which may, in turn, facilitate infection with sexually acquired human immunodeficiency virus, coincident with the expansion of this epidemic in Africa. Syphilis complications are also almost certain to include adverse pregnancy outcome due to maternal syphilis. The rising trend in genital syphilis and GUD, and the probable increase in associated adverse sequellae, require that prevention and control of sexually transmitted diseases should be made a high priority. C1 NIAID,DIV AIDS,6003 EXECUT BLVD,RM 240P,BETHESDA,MD 20892. YALGADO OUEDRAOGO HOSP,OUAGADOUGOU,BURKINA FASO. COLUMBIA UNIV,SCH PUBL HLTH,DIV EPIDEMIOL,NEW YORK,NY 10027. MONTEFIORE MED CTR,ALBERT EINSTEIN COLL,DEPT EPIDEMIOL & SOCIAL MED,BRONX,NY. MONTEFIORE ME CTR,ALBERT EINSTEIN COLL,DEPT PEDIAT,BRONX,NY. OI Vermund, Sten/0000-0001-7289-8698 NR 49 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD JUN PY 1991 VL 20 IS 2 BP 490 EP 494 DI 10.1093/ije/20.2.490 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA FX110 UT WOS:A1991FX11000026 PM 1917254 ER PT J AU HERMAN, AA SOSKOLNE, CL MALCOE, L LILIENFELD, DE AF HERMAN, AA SOSKOLNE, CL MALCOE, L LILIENFELD, DE TI GUIDELINES ON ETHICS FOR EPIDEMIOLOGISTS SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Letter RP HERMAN, AA (reprint author), NICHHD,DIV PREVENT RES,EXEC PLAZA N BLDG,ROOM 640,BETHESDA,MD 20892, USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD JUN PY 1991 VL 20 IS 2 BP 571 EP 572 DI 10.1093/ije/20.2.571 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA FX110 UT WOS:A1991FX11000039 PM 1917267 ER PT J AU JOYCE, EM AF JOYCE, EM TI CEREBRAL BLOOD-FLOW AND METABOLISM IN AFFECTIVE-DISORDERS SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE CEREBRAL BLOOD FLOW; CEREBRAL METABOLISM; AFFECTIVE DISORDERS ID POSITRON EMISSION TOMOGRAPHY; GLUCOSE-UTILIZATION; DEPRESSED-PATIENTS; MOOD DISORDERS; OXYGEN-CONSUMPTION; STROKE PATIENTS; BRAIN-FUNCTION; SCHIZOPHRENIA; CORTEX; COMMON RP JOYCE, EM (reprint author), NIAAA,CLIN STUDIES LAB,NIH BLDG 10,BETHESDA,MD 20892, USA. NR 53 TC 4 Z9 4 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD JUN PY 1991 VL 6 IS 6 BP 423 EP 430 DI 10.1002/gps.930060615 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA FV500 UT WOS:A1991FV50000014 ER PT J AU KOTAKE, S REDMOND, TM WIGGERT, B VISTICA, B SANUI, H CHADER, GJ GERY, I AF KOTAKE, S REDMOND, TM WIGGERT, B VISTICA, B SANUI, H CHADER, GJ GERY, I TI UNUSUAL IMMUNOLOGICAL PROPERTIES OF THE UVEITOGENIC INTERPHOTORECEPTOR RETINOID-BINDING PROTEIN-DERIVED PEPTIDE R23 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE INTERPHOTORECEPTOR RETINOID-BINDING PROTEIN (IRBP); EXPERIMENTAL AUTOIMMUNE UVEORETINITIS (EAU); EXPERIMENTAL AUTOIMMUNE PINEALITIS (EAP); IRBP-DERIVED PEPTIDES; IMMUNOLOGICAL PROPERTIES OF PEPTIDES ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; LEWIS RATS; S-ANTIGEN; IRBP; IMMUNODOMINANT; DETERMINANT; UVEITIS; IDENTIFICATION; IMMUNIZATION; DISSOCIATION AB Peptide R23, consisting of residues 1091-1115 of bovine interphotoreceptor retinoid-binding protein (IRBP), had some unusual immunologic properties in Lewis rats. The peptide induced experimental autoimmune uveoretinitis and pinealitis in these rats, but only at high doses. The minimal immunopathogenic dose was found to be 100 nmol/rat. On the other hand, R23 was highly immunogenic in Lewis rats, producing cellular immunity, as measured by the lymphocyte proliferation assay, with a minimal dose of 1 nmol/rat. This unusual dissociation between the uveitogenic and immunogenic activities of R23 was attributed to different sites on the peptide, stimulating either the lymphocytes which induce disease or those which vigorously proliferate in culture. The potent immunogenicity of R23 was consistent with the peptide being immunodominant, as demonstrated by its capacity to be recognized by lymphocytes sensitized against whole IRBP and to stimulate these cells in culture to proliferate and acquire uveitogenic capacity. Likewise, lymphocytes sensitized against R23 are stimulated in culture by whole IRBP. Unexpectedly, peptide R23 was inferior to whole IRBP in its capacity to stimulate uveitogenicity in R23-sensitized lymphocytes. This finding also was attributed to the preferential stimulation by R23 of the lymphocytes specific for the putative "nonuveitogenic" site on the peptide. Peptide R23 also differs from the other tested bovine IRBP-derived peptides in the specificity of its antibodies. Unlike antibodies to the other peptides, those to R23 showed a strong cross reactivity toward whole IRBP. C1 NEI,IMMUNOL LAB,BLDG 10,ROOM 10N210,BETHESDA,MD 20892. NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. OI Redmond, T. Michael/0000-0002-1813-5291 NR 28 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 1991 VL 32 IS 7 BP 2058 EP 2064 PG 7 WC Ophthalmology SC Ophthalmology GA FT923 UT WOS:A1991FT92300015 PM 2055698 ER PT J AU ROBINSON, DM AF ROBINSON, DM TI SCIENTISTS AS LEADERS SO ISSUES IN SCIENCE AND TECHNOLOGY LA English DT Editorial Material RP ROBINSON, DM (reprint author), NIH,SCI PROGRAM,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0748-5492 J9 ISSUES SCI TECHNOL JI Issues Sci. Technol. PD SUM PY 1991 VL 7 IS 4 BP 31 EP 31 PG 1 WC Engineering, Multidisciplinary; Engineering, Industrial; Multidisciplinary Sciences; Social Issues SC Engineering; Science & Technology - Other Topics; Social Issues GA FW308 UT WOS:A1991FW30800040 ER PT J AU PAUL, W AF PAUL, W TI IL-6 - A MULTIFUNCTIONAL REGULATOR OF IMMUNITY AND INFLAMMATION SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Editorial Material RP PAUL, W (reprint author), NIAID,IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE CANCER ASSOCIATION PI TOKYO PA EDITORIAL OFFICE 7TH FLOOR, JOHKOH BLDG 2-23-11, KOISHIKAWA, TOKYO 112, JAPAN SN 0910-5050 J9 JPN J CANCER RES JI Jpn. J. Cancer Res. PD JUN PY 1991 VL 82 IS 6 BP UR1 EP UR1 PG 1 WC Oncology SC Oncology GA FR934 UT WOS:A1991FR93400001 ER PT J AU AMBRUS, JL HANEIWICH, S CHESKY, L MCFARLAND, P PETERS, MG ENGLER, RJ AF AMBRUS, JL HANEIWICH, S CHESKY, L MCFARLAND, P PETERS, MG ENGLER, RJ TI ABNORMAL RESPONSE TO A HUMAN B-CELL GROWTH-FACTOR IN PATIENTS WITH COMMON VARIABLE IMMUNODEFICIENCY (CVI) SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article ID NECROSIS FACTOR-ALPHA; T-T HYBRIDOMA; LYMPHOCYTES-B; INOSITOL 1,4,5-TRISPHOSPHATE; HUMORAL IMMUNODEFICIENCY; VARIED IMMUNODEFICIENCY; INTERLEUKIN-2 RECEPTORS; FACTOR BCGF; DIFFERENTIATION; HYPOGAMMAGLOBULINEMIA AB Patients with common variable immunodeficiency (CVI) generally fail to produce antigen-specific IgG. We have identified a lymphokine called high molecular weight B cell growth factor (HMW BCGF) that expands an IgG-producing subpopulation of B cells. The B cells from 15 of 16 patients with CVI evaluated in this study failed to proliferate to HMW BCGF, although they proliferated normally to another BCGF, low molecular weight BCGF (LMW BCGF). Nevertheless, 11 patients had more than normal numbers of B cells expressing HMW BCGF receptors. The HMW BCGF receptors on the B cells of three patients with CVI studied were the same molecular weight as the normal HMW BCGF receptor. Examination of B cells from four patients with CVI for intracellular signals produced in normal B cells after stimulation with HMW BCGF revealed that B cells from patients with CVI failed to developed significant increases in cyclic adenosine monophosphate or phosphoinositides after HMW BCGF stimulation. However, cytoplasmic phosphoinositides in the B cells from all four patients with CVI were already increased above what is observed in normal B cells before stimulation with HMW BCGF (either freshly isolated or Staphylococcus aureus Cowan I-activated B cell). Thus, the failure of B cells from patients with CVI to respond to HMW BCGF may be related to their abnormal activation in vivo. Since HMW BCGF expands a subpopulation of memory B cells, the inability of CVI B cells to respond to HMW BCGF may contribute to their abnormal secondary responses to antigens. C1 NIAID,BETHESDA,MD 20892. MED UNIV S CAROLINA,CHARLESTON,SC 29425. WASHINGTON UNIV,SCH MED,DEPT INTERNAL MED,DIV GASTROENTEROL,ST LOUIS,MO 63110. WALTER REED ARMY MED CTR,DIV ALLERGY & IMMUNIZAT,WASHINGTON,DC 20307. RP AMBRUS, JL (reprint author), WASHINGTON UNIV,JEWISH HOSP ST LOUIS,SCH MED,DEPT MED,DIV RHEUMATOL,660 S EUCLID,CAMPUS BOX 8045,ST LOUIS,MO 63110, USA. NR 54 TC 4 Z9 4 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 1991 VL 87 IS 6 BP 1138 EP 1149 DI 10.1016/0091-6749(91)92160-3 PG 12 WC Allergy; Immunology SC Allergy; Immunology GA FR066 UT WOS:A1991FR06600014 PM 1646248 ER PT J AU THURAU, SR CHAN, CC SUH, E NUSSENBLATT, RB AF THURAU, SR CHAN, CC SUH, E NUSSENBLATT, RB TI INDUCTION OF ORAL TOLERANCE TO S-ANTIGEN INDUCED EXPERIMENTAL AUTOIMMUNE UVEITIS BY A UVEITOGENIC 20MER PEPTIDE SO JOURNAL OF AUTOIMMUNITY LA English DT Article ID MYELIN BASIC-PROTEIN; LEWIS RATS; UVEORETINITIS; ENCEPHALOMYELITIS; IDENTIFICATION; SUPPRESSION; INHIBITION; SITE C1 NEI,IMMUNOL LAB,BETHESDA,MD 20892. NR 29 TC 42 Z9 43 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD JUN PY 1991 VL 4 IS 3 BP 507 EP 516 DI 10.1016/0896-8411(91)90162-6 PG 10 WC Immunology SC Immunology GA FU366 UT WOS:A1991FU36600009 PM 1910426 ER PT J AU MARTIN, KA DAVIS, MA AUSTIN, S AF MARTIN, KA DAVIS, MA AUSTIN, S TI FINE-STRUCTURE ANALYSIS OF THE P1-PLASMID PARTITION SITE SO JOURNAL OF BACTERIOLOGY LA English DT Article ID UNIT-COPY MINIPLASMIDS; CENTROMERE-LIKE SITE; P1 PLASMID; DAUGHTER CELLS; HOST FACTOR; PROTEIN; REGION; SYSTEM AB P1 plasmid partition requires two plasmid-encoded Par proteins and a cis-acting site. The site, parS, lies in a region consisting of a 13-bp palindrome and an adjacent AT-rich sequence. A series of point mutations were analyzed for their effects on partition site activity. The results indicated that only the left arm of the palindrome and some adjacent bases were needed. The limits of the functional site were further refined to a maximum of 22 bp, which includes binding sites for the P1 ParB protein. Mutations in the 22-bp site cause concomitant defects in partition and the ability to exert partition-mediated incompatibility. Like the region immediately to the left of the 22-bp region, the right arm of the palindrome is not essential for partition but does contain information that affects the specificity of incompatibility. C1 NCI,FREDERICK CANC RES & DEV CTR,CHROMOSOME BIOL LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 13 TC 31 Z9 31 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 JUN PY 1991 VL 173 IS 12 BP 3630 EP 3634 PG 5 WC Microbiology SC Microbiology GA FT129 UT WOS:A1991FT12900004 PM 2050624 ER PT J AU GENTRY, D XIAO, H BURGESS, R CASHEL, M AF GENTRY, D XIAO, H BURGESS, R CASHEL, M TI THE OMEGA SUBUNIT OF ESCHERICHIA-COLI K-12 RNA-POLYMERASE IS NOT REQUIRED FOR STRINGENT RNA CONTROL INVIVO SO JOURNAL OF BACTERIOLOGY LA English DT Note ID PROMOTER SELECTIVITY; PPGPP; GENE; SPOT AB Igarashi et al. (K. Igarashi, N. Fujita, and A. Ishihama, Nucleic Acids Res. 17:8755-8765, 1989) reported that the omega (omega) subunit of Escherichia coli RNA polymerase was required for stringent control as judged by in vitro transcription assays in the presence and absence of guanosine 3',5'-bispyrophosphate (ppGpp). This conclusion predicts that a deletion of the omega gene (designated rpoZ or spoS) should show a relaxed RNA control phenotype in vivo. However, we find that wild-type stringent control of stable RNA accumulation is unaffected by a spoS null allele that abolishes cellular production of the omega protein. We conclude that omega protein is not necessary for the operation of the stringent RNA control response. C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. UNIV WISCONSIN,MCARDLE LAB CANC RES,MADISON,WI 53706. NR 14 TC 52 Z9 52 U1 0 U2 2 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 JUN PY 1991 VL 173 IS 12 BP 3901 EP 3903 PG 3 WC Microbiology SC Microbiology GA FT129 UT WOS:A1991FT12900038 PM 1711031 ER PT J AU ZATZ, M AF ZATZ, M TI LIGHT AND NOREPINEPHRINE SIMILARLY PREVENT DAMPING OF THE MELATONIN RHYTHM IN CULTURED CHICK PINEAL CELLS - REGULATION OF COUPLING BETWEEN THE PACEMAKER AND OVERT RHYTHMS SO JOURNAL OF BIOLOGICAL RHYTHMS LA English DT Article ID N-ACETYLTRANSFERASE ACTIVITY; PHOTOENDOCRINE TRANSDUCTION; CIRCADIAN OSCILLATOR; ADENYLATE-CYCLASE; PERTUSSIS TOXIN; G-PROTEINS; GLAND; FORSKOLIN; AMP; INVITRO AB The circadian rhythm of melatonin output displayed by chick pineal cells in static culture damps rapidly in constant red light (RR). This can be seen in the first cycle following a switch from a cycle of 12 hr white light (L) and 12 hr red light (R) to RR. Melatonin output is higher during the "day" in R than it is in L, but higher that next night (in R) after daytime L than after daytime R. This effect might be due entirely to the entraining effect of L. Alternatively, the higher nocturnal output after daytime L could be related to the acute suppression caused by L; it might be a "rebound" phenomenon. These alternative hypotheses differ in their predictions for the effects of norepinephrine (NE) and pertussis toxin (PT). Previous results dissociated the acute and entraining effects of L: PT blocks the acute effect but not the entraining effect of L. NE mimics the acute effect of L (and is blocked by PT), but not the entraining effect. If L prevents damping entirely by entrainment, then NE should not mimic and PT should not block this same-cycle effect of daytime L on nocturnal melatonin output. However, the present research found that NE did mimic and PT did block this effect, indicating that the ability of L to prevent damping is mediated by a same-cycle "rebound" following L's acute inhibition of melatonin production. Furthermore, NE enhanced the "rebound" effect of daytime L, and cycles substituting NE for L were effective in driving the melatonin rhythm. Lowering extracellular potassium did not induce a "rebound," and adding exogenous melatonin did not prevent one. The difference between nocturnal melatonin synthesis after daytime R and that after daytime L or NE implies regulation of coupling between the output of the circadian pacemaker and melatonin production. These results also suggest a role for NE in regulating and maintaining the expression of the melatonin rhythm. C1 NIMH,CELL BIOL LAB,BIOCHEM PHARMACOL SECT,BETHESDA,MD 20892. NR 23 TC 19 Z9 19 U1 0 U2 0 PU SAGE SCIENCE PRESS PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0748-7304 J9 J BIOL RHYTHM JI J. Biol. Rhythms PD SUM PY 1991 VL 6 IS 2 BP 137 EP 147 DI 10.1177/074873049100600204 PG 11 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA FQ233 UT WOS:A1991FQ23300004 PM 1773087 ER PT J AU NATHAN, C SPORN, M AF NATHAN, C SPORN, M TI CYTOKINES IN CONTEXT SO JOURNAL OF CELL BIOLOGY LA English DT Review ID TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR-BETA; CELL-ADHESION RECEPTORS; COLONY-STIMULATING FACTOR; EXTRACELLULAR-MATRIX; HUMAN-NEUTROPHILS; ENDOTHELIAL-CELLS; T-CELLS; INTERFERON-GAMMA; HUMAN-MONOCYTES C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. RP NATHAN, C (reprint author), CORNELL UNIV,MED CTR,COLL MED,DEPT MED,DIV HEMATOL ONCOL,BEATRICE & SAMUEL A SEAVER LAB,NEW YORK,NY 10021, USA. FU NCI NIH HHS [CA-43610, CA-45218] NR 84 TC 745 Z9 747 U1 0 U2 13 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUN PY 1991 VL 113 IS 5 BP 981 EP 986 DI 10.1083/jcb.113.5.981 PG 6 WC Cell Biology SC Cell Biology GA FN341 UT WOS:A1991FN34100001 PM 2040651 ER PT J AU SHIMIZU, Y NEWMAN, W GOPAL, TV HORGAN, KJ GRABER, N BEALL, LD VANSEVENTER, GA SHAW, S AF SHIMIZU, Y NEWMAN, W GOPAL, TV HORGAN, KJ GRABER, N BEALL, LD VANSEVENTER, GA SHAW, S TI 4 MOLECULAR PATHWAYS OF T-CELL ADHESION TO ENDOTHELIAL-CELLS - ROLES OF LFA-1, VCAM-1, AND ELAM-1 AND CHANGES IN PATHWAY HIERARCHY UNDER DIFFERENT ACTIVATION CONDITIONS SO JOURNAL OF CELL BIOLOGY LA English DT Article ID NODE HOMING RECEPTOR; LEUKOCYTE ADHESION; HELPER-INDUCER; LYMPHOCYTES-T; ANTIGEN-1 LFA-1; FIBRONECTIN; ICAM-1; LIGAND; IDENTIFICATION; EXPRESSION AB T cell adhesion to endothelium is critical to lymphocyte recirculation and influx into sites of inflammation. We have systematically analyzed the role of four receptor/ligand interactions that mediate adhesion of peripheral human CD4+ T cells to cultured human umbilical vein endothelial cells (HUVEC): T cell LFA-1 binding to ICAM-1 and an alternative ligand ("ICAM-X"), T cell VLA-4 binding to VCAM-1, and T cell binding to ELAM-1. Contributions of these four pathways depend on the activation state of both the T cell and HUVEC, and the differentiation state of the T cell. ELAM-1 plays a significant role in mediating adhesion of resting CD4+ T cells to activated HUVEC. LFA-1 adhesion dominates with PMA-activated T cells but the strength and the pre-dominant LFA-1 ligand is determined by the activation state of the HUVEC; while ICAM-1 is the dominant ligand on IL-1-induced HUVEC, "ICAM-X" dominates binding to uninduced HUVEC. Adhesion via VLA-4 depends on induction of its ligand VCAM-1 on activated HUVEC; PMA activation of T cells augments VLA-4-mediated adhesion, both in the model of T/HUVEC binding and in a simplified model of T cell adhesion to VCAM-1-transfected L cells. Unlike LFA-1 and VLA-4, ELAM-1-mediated adhesion is not increased by T cell activation. Differential expression of adhesion molecules on CD4+ T cell subsets understood to be naive and memory cells also regulates T/HUVEC adhesion. Naive T cell adhesion to HUVEC is mediated predominantly by LFA-1 with little or no involvement of the VLA-4 and ELAM-1 pathways. In contrast, memory T cells bind better to HUVEC and utilize all four pathways. These studies demonstrate that there are at least four molecular pathways mediating T/HUVEC adhesion and that the dominance/hierarchy of these pathways varies dramatically with the activation state of the interacting cells and the differentiation state of the T cell. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. OTSUKA AMER PHARMACEUT INC,DEPT IMMUNOL,ROCKVILLE,MD 20850. OTSUKA AMER PHARMACEUT INC,DEPT MOLEC BIOL,ROCKVILLE,MD 20850. OI Shimizu, Yoji/0000-0001-9760-0288 NR 57 TC 374 Z9 376 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUN PY 1991 VL 113 IS 5 BP 1203 EP 1212 DI 10.1083/jcb.113.5.1203 PG 10 WC Cell Biology SC Cell Biology GA FN341 UT WOS:A1991FN34100020 PM 1710227 ER PT J AU MAUVIEL, A REDINI, F HARTMANN, DJ PUJOL, JP EVANS, CH AF MAUVIEL, A REDINI, F HARTMANN, DJ PUJOL, JP EVANS, CH TI MODULATION OF HUMAN DERMAL FIBROBLAST EXTRACELLULAR-MATRIX METABOLISM BY THE LYMPHOKINE LEUKOREGULIN SO JOURNAL OF CELL BIOLOGY LA English DT Article ID GROWTH FACTOR-BETA; COLLAGEN GENE-EXPRESSION; NECROSIS-FACTOR-ALPHA; SYNOVIAL FIBROBLASTS; INTERLEUKIN-1; CELLS; FIBRONECTIN; PROLIFERATION; PURIFICATION; INHIBITION AB The effect of leukoregulin, a 50-kD lymphokine with unique antitumor properties, was studied in vitro on several fibroblast functions. Leukoregulin did not inhibit fibroblast proliferation, as measured by cell enumeration and [H-3]thymidine incorporation, and had no cytotoxic effect in terms of increased membrane permeability detected by trypan blue exclusion, two of the major leukoregulin actions on tumor cells. Leukoregulin induced a dose-dependent decrease in collagen synthesis, demonstrated by decreased [H-3]proline incorporation into collagenase-digestible protein, as early as 6 h after the addition of the lymphokine to human fibroblasts. Leukoregulin inhibited the synthesis of both type I and type III collagen, as measured by SDS-PAGE and by specific radioimmunoassay. Neutralizing antibodies to interleukin-1-alpha, interleukin-1-beta, tumor necrosis factor-alpha, and interferon-gamma failed to alter the effect of leukoregulin on collagen synthesis, attesting that leukoregulin action was not due to contamination by these cytokines. Inhibition of collagen synthesis occurred concomitantly with increased secretion of prostaglandin E2 and a transient rise in intracellular cyclic AMP content, peaking at 6 h. However, blocking prostaglandin synthesis with indomethacin did not counteract inhibition of collagen synthesis by leukoregulin, demonstrating independence of this action of leukoregulin from cyclooxygenase metabolites. Leukoregulin also stimulated glycosaminoglycan production in a dose-dependent manner, affecting the synthesis of hyaluronic acid as the major fibroblast-derived extracellular glycosaminoglycan. In addition, secretion of neutral proteases (collagenase, elastase, caseinase) was increased. These observations indicate that leukoregulin is able to regulate synthesis of molecules critical to the deposition of the extracellular matrix by nontransformed nonmalignant fibroblasts. C1 CHU COTE NACRE,BIOCHIM TISSU CONJONCTIF LAB,F-4040 CAEN,FRANCE. NCI,DIV CANC ETIOL,BIOL LAB,TUMOR BIOL SECT,BETHESDA,MD 20892. RI MAUVIEL, Alain/F-6251-2013; REDINI, Francoise/K-7981-2015 NR 33 TC 15 Z9 15 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUN PY 1991 VL 113 IS 6 BP 1455 EP 1462 DI 10.1083/jcb.113.6.1455 PG 8 WC Cell Biology SC Cell Biology GA FQ772 UT WOS:A1991FQ77200019 PM 1646205 ER PT J AU WOLFFE, AP AF WOLFFE, AP TI IMPLICATIONS OF DNA-REPLICATION FOR EUKARYOTIC GENE-EXPRESSION SO JOURNAL OF CELL SCIENCE LA English DT Editorial Material DE REPLICATION; CHROMATIN; TRANSCRIPTION ID NEWLY SYNTHESIZED HISTONES; EARLY DROSOPHILA DEVELOPMENT; RIBOSOMAL-RNA GENES; TRANSCRIPTION COMPLEX; POSITIONED NUCLEOSOMES; CELL-DIFFERENTIATION; TEMPORAL-ORDER; XENOPUS EGGS; INVITRO; CHROMATIN AB DNA replication has a key role in many developmental processes. Recent progress in understanding events at the replication fork suggests mechanisms for both establishing and maintaining programs of eukaryotic gene activity. In this review, I discuss the consequences of replication fork passage for pre-existing chromatin structures and describe how the mechanism of nucleosome assembly at the replication fork may facilitate the formation of either transcriptionally active or repressed chromatin. RP WOLFFE, AP (reprint author), NIDDK,MOLEC BIOL LAB,BLDG 6,RM 131,BETHESDA,MD 20892, USA. NR 74 TC 96 Z9 96 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 JUN PY 1991 VL 99 BP 201 EP 206 PN 2 PG 6 WC Cell Biology SC Cell Biology GA FT526 UT WOS:A1991FT52600001 PM 1885667 ER PT J AU MILLER, DS SYKES, DB AF MILLER, DS SYKES, DB TI STIMULATION OF PROTEIN-SYNTHESIS BY INTERNALIZED INSULIN SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID RECEPTOR-MEDIATED ENDOCYTOSIS; XENOPUS OOCYTES; POLYPEPTIDE HORMONES; INTRACELLULAR ROLE; GROWTH-FACTORS; TARGET-CELLS; MICROINJECTION; VITELLOGENIN; ASSOCIATION; MECHANISMS AB Previous studies showed that microinjected insulin stimulates transcription and translation in Stage IV Xenopus oocytes by acting at nuclear and cytoplasmic sites (Miller, D.S., 1988, 1989). The present report is concerned with the question of whether hormone, internalized from an external medium, can act on those sites to alter cell function. Both intracellular accumulation of undegraded I-125-insulin and insulin-stimulated S-35-methionine incorporation into oocyte protein were measured. Anti-insulin antiserum and purified anti-insulin antibody were microinjected into the cytoplasm of insulin-exposed cells to determine if insulin derived from the medium acted through internal sites. In cells exposed for 2 h to 7 or 70 nM external insulin, methionine incorporation was stimulated, but intracellular hormone accumulation was minimal and microinjected antibody was without effect. In cells exposed for 24 h, methionine incorporation again increased, but now accumulation of undegraded, intracellular hormone was substantial (2.6 and 25.3 fmol with 7 and 70 nM, respectively), and microinjected anti-insulin antibody significantly reduced the insulin-stimulated component of incorporation; basal incorporation was not affected. For cells exposed to 70 nM insulin for 24 h, inhibition of the insulin-stimulated component was maximal at 39%. Thus under those conditions, about 40% of insulin's effects were mediated by the internal sites. Together, the data show that inhibition of insulin-stimulated protein synthesis by microinjected antibody was associated with the intracellular accumulation of insulin. They indicate that when oocytes are exposed to external insulin, hormone eventually gains access to intracellular sites of action and through these stimulates translation. Control of translation appears to be shared between the internal sites and the surface receptor. RP MILLER, DS (reprint author), NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709, USA. NR 21 TC 11 Z9 11 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUN PY 1991 VL 147 IS 3 BP 487 EP 494 DI 10.1002/jcp.1041470315 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA FX308 UT WOS:A1991FX30800014 PM 2066368 ER PT J AU NYOMBA, BL SWINBURN, BA OSSOWSKI, VM BOYCE, VL BOGARDUS, C MOTT, DM AF NYOMBA, BL SWINBURN, BA OSSOWSKI, VM BOYCE, VL BOGARDUS, C MOTT, DM TI INSULIN-SENSITIVE TYROSINE KINASE-ACTIVITY CHANGES IN PARALLEL WITH PLASMA-INSULIN AND GLUCOSE-CONCENTRATIONS IN HUMANS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DEPENDENT DIABETES-MELLITUS; RECEPTOR KINASE; SKELETAL-MUSCLE; RAT-LIVER; INVIVO; BINDING; HEPATOCYTES; RESISTANCE; ADIPOCYTES; ACTIVATION AB Insulin receptor tyrosine kinase is an important step in insulin action. We examined the relationship between diet-induced changes in glucose metabolism and changes in skeletal muscle insulin-sensitive tyrosine kinase activity in 12 nondiabetic subjects. Subjects were fed a traditional, high carbohydrate Pima Indian diet and a modern, high fat western diet for 2 weeks in a randomized cross-over design. At the end of each dietary period, glucose tolerance was assessed, insulin sensitivity (S(I)) was estimated by Bergman's minimal model method, and insulin receptor concentration and tyrosine kinase activity were determined on lectin-purified extracts from quadriceps femoris muscle. Compared to the traditional diet, the modern diet was associated with a deterioration of glucose tolerance and an increase in glucose-induced plasma insulin levels. As expected, S(I) changes were associated with opposite changes in plasma insulin levels. However, the changes in maximal tyrosine kinase activity were negatively correlated with changes in S(I) (r = -0.69; P < 0.01) and positively correlated with changes in plasma glucose (r = 0.70; P < 0.01) and insulin response to glucose (r = 0.57; P < 0.025). These results suggest that the site of diet-induced changes in insulin action is beyond the insulin-sensitive tyrosine kinase. The results further suggest that the kinase activity is modulated by prevailing plasma insulin levels. RP NYOMBA, BL (reprint author), NIDDKD, CLIN DIABET & NUTR SECT, 4212 N 16TH ST, ROOM 541, PHOENIX, AZ 85016 USA. NR 31 TC 5 Z9 5 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 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 1991 VL 72 IS 6 BP 1212 EP 1219 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FM319 UT WOS:A1991FM31900008 PM 2026743 ER PT J AU JOSEPHVANDERPOOL, JR ROSENTHAL, NE CHROUSOS, GP WEHR, TA SKWERER, R KASPER, S GOLD, PW AF JOSEPHVANDERPOOL, JR ROSENTHAL, NE CHROUSOS, GP WEHR, TA SKWERER, R KASPER, S GOLD, PW TI ABNORMAL PITUITARY-ADRENAL RESPONSES TO CORTICOTROPIN-RELEASING HORMONE IN PATIENTS WITH SEASONAL AFFECTIVE-DISORDER - CLINICAL AND PATHOPHYSIOLOGICAL IMPLICATIONS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID CORTISOL AB CRH has been shown to produce increased locomotion, arousal, and anorexia in experimental animals. A deficiency of CRH in patients with seasonal affective disorder could contribute to the characteristic lethargy, hypersomnia, and hyperphagia characteristic of this illness. To test this hypothesis, we studied basal plasma ACTH and cortisol levels and their responses to ovine CRH in controls and depressed patients with seasonal affective disorder before and after light treatment. Untreated seasonal affective disorder patients showed normal basal plasma cortisol and ACTH levels, but their responses to CRH tended to be delayed and were significantly reduced. When patients were studied after 9 days of light treatment, a significant increase in plasma ACTH and cortisol responses to CRH was observed. Our findings in untreated patients with seasonal affective disorder are similar to those in patients with Cushing's disease 2 weeks after transsphenoidal hypophysectomy, who uniformly show sustained suppression of their CRH neuron because of long-standing hypercortisolism. This findings suggest that the CRH neuron of patients with seasonal affective disorder is hypofunctional. We postulate that the clinical symptomatology in patients with seasonal affective disorder could reflect deficient activity of this important arousal-producing system. RP JOSEPHVANDERPOOL, JR (reprint author), NIMH, CLIN PSYCHOBIOL BRANCH, BLDG 10-4S239, 9000 ROCKVILLE PIKE, BETHESDA, MD 20009 USA. NR 22 TC 74 Z9 75 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 1991 VL 72 IS 6 BP 1382 EP 1387 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FM319 UT WOS:A1991FM31900036 PM 1851185 ER PT J AU ABE, T KOBAYASHI, N YOSHIMURA, K TRAPNELL, BC KIM, H HUBBARD, RC BREWER, MT THOMPSON, RC CRYSTAL, RG AF ABE, T KOBAYASHI, N YOSHIMURA, K TRAPNELL, BC KIM, H HUBBARD, RC BREWER, MT THOMPSON, RC CRYSTAL, RG TI EXPRESSION OF THE SECRETORY LEUKOPROTEASE INHIBITOR GENE IN EPITHELIAL-CELLS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE POLYMORPHISM; TRANSCRIPTION; MESSENGER RNA TRANSCRIPT STABILITY; DNASE-I HYPERSENSITIVITY SITE; 5' FLANKING REGION ID BRONCHIAL PROTEASE INHIBITOR; STABLE PROTEINASE-INHIBITOR; AMINO-ACID SEQUENCE; ALPHA-1-ANTITRYPSIN GENE; HUMAN-LUNG; TRANSCRIPTIONAL REGULATION; MONONUCLEAR PHAGOCYTES; LEUKOCYTE ELASTASE; RESPIRATORY-TRACT; POTENT INHIBITOR AB The secretory leukoprotease inhibitor (SLPI) gene codes for a 12-kD protein that within the lung protects the airway epithelium from neutrophil elastase. Screening of 228 alleles in 114 individuals for sequence differences by RNase protection of genomic DNA revealed no detectable polymorphisms in SLPI gene exons II-IV. SLPI gene expression in the lung was demonstrated by identifying SLPI mRNA transcripts in bronchial epithelial cells freshly isolated from normals. Cell lines derived from mucosal surfaces (HS-24 bronchial squamous cell carcinoma, HeLa cervical carcinoma) actively transcribe the SLPI gene and contain SLPI mRNA transcripts, while lung fibroblasts demonstrate no evidence of SLPI gene expression. SLPI mRNA transcripts appear to be relatively stable, with mRNA levels only mildly affected by inhibition of RNA synthesis. Chromatin DNA of HS-24 cells demonstrates two DNase I hypersensitivity sites within the 5' flanking region of exon I of the SLPI gene, whereas fibroblast chromatin has no DNase I accessible sites in the same region. Further analysis of the 5' flanking region demonstrated two contiguous transcription start sites, CAAT and TATA boxes, and several potential regions of known DNA binding proteins. Overall, the SLPI gene appears to be a relatively nonpolymorphic, stable gene that is constitutively expressed at specific tissue sites, but has the potential to be modulated at both the transcriptional and posttranscriptional levels. C1 NHLBI,PULM BRANCH,BLDG 10,ROOM 6D03,BETHESDA,MD 20892. SYNERGEN,BOULDER,CO 80301. NR 51 TC 120 Z9 122 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 1991 VL 87 IS 6 BP 2207 EP 2215 DI 10.1172/JCI115255 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA FP851 UT WOS:A1991FP85100045 PM 1674946 ER PT J AU DORWARD, DW SCHWAN, TG GARON, CF AF DORWARD, DW SCHWAN, TG GARON, CF TI IMMUNE CAPTURE AND DETECTION OF BORRELIA-BURGDORFERI ANTIGENS IN URINE, BLOOD, OR TISSUES FROM INFECTED TICKS, MICE, DOGS, AND HUMANS SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID LYME-DISEASE SPIROCHETE; NEISSERIA-GONORRHOEAE; PEROMYSCUS-LEUCOPUS; INVITRO CULTIVATION; MOLECULAR ANALYSIS; PROTEINS; ANTIBODY; RESPONSES; DIAGNOSIS; BLADDER AB Current biological and serological techniques for demonstrating infections by Borrelia burgdorferi can be inconclusive. In order to monitor Lyme borreliosis, we developed a rapid and sensitive assay for B. burgdorferi antigens in infected hosts. Polyclonal rabbit antisera were raised against membrane vesicles and an 83-kDa vesicle-associated protein band that was purified from in vitro B. burgdorferi cultures. Immunoglobulin G (IgG) antibodies were recovered from these sera and tested for a species-specific reaction with several geographically diverse Borrelia isolates by immunoblot analysis. Parlodion-coated electron microscope grids were activated with anti-vesicle F(ab')2 fragments and then incubated with confirmed or experimental sources of spirochetal antigens. Such sources included cultured spirochetes; spirochete culture supernatants; samples of urine, blood, or serum from mice, dogs, and humans; triturates of Ixodes ticks; and bladder, spleen, liver, kidney, heart, or brain tissues from infected or control mice. Captured antigens were assayed by immune electron microscopy by using anti-83-kDa IgG antibodies and protein A-colloidal gold conjugates. The results indicated that B. burgdorferi appears to shed surface antigens which are readily detectable in urine, blood, and several organs from infected hosts. Such antigens were detectable in mouse urine at dilutions exceeding 10(-6). Intact spirochetes were frequently observed on grids incubated with blood, spleen, or bladder preparations, and B. burgdorferi was reisolated from the urinary bladders of all experimentally infected mice. These results indicated that B. burgdorferi antigens arise in a variety of host materials. Such antigens can be captured and identified with specific polyclonal antibodies, providing a sensitive assay for monitoring and studying Lyme borreliosis. RP DORWARD, DW (reprint author), NIAID,ROCKY MT LABS,VECTORS & PATHOGENS LAB,HAMILTON,MT 59840, USA. NR 36 TC 80 Z9 80 U1 0 U2 4 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 JUN PY 1991 VL 29 IS 6 BP 1162 EP 1170 PG 9 WC Microbiology SC Microbiology GA FM520 UT WOS:A1991FM52000014 PM 1864935 ER PT J AU CLEMENTS, ML BELSHE, RB KING, J NEWMAN, F WESTBLOM, TU TIERNEY, EL LONDON, WT MURPHY, BR AF CLEMENTS, ML BELSHE, RB KING, J NEWMAN, F WESTBLOM, TU TIERNEY, EL LONDON, WT MURPHY, BR TI EVALUATION OF BOVINE, COLD-ADAPTED HUMAN, AND WILD-TYPE HUMAN PARAINFLUENZA TYPE-3 VIRUSES IN ADULT VOLUNTEERS AND IN CHIMPANZEES SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID INFLUENZA-A-VIRUS; TEMPERATURE-SENSITIVE PHENOTYPE; LINKED IMMUNOSORBENT-ASSAY; RESPIRATORY-TRACT DISEASE; IMMUNOLOGICAL RESPONSE; INACTIVATED VACCINE; RECOMBINANT VIRUSES; WEANLING HAMSTERS; REASSORTANT VIRUS; YOUNG-CHILDREN AB In an attempt to evaluate the level of attenuation of live parainfluenza type 3 virus (PIV3) vaccine candidates, we compared the responses of partially immune adult volunteers inoculated intranasally with 10(6) to 10(7) 50% tissue culture infective dose (TCID50) of bovine PIV3 (n = 18) or cold-adapted (ca) PIV3 (n = 37) with those of 28 adults administered 10(6) to 10(7) TCID50 of wild-type PIV3. The candidate vaccine viruses and the wild-type virus were avirulent and poorly infectious for these adults even though all of them had a low level of nasal antibodies to PIV3. To determine whether the ca PIV3 was attenuated, we then administered 10(4) TCID50 of ca PIV3 (cold-passage 12) or wild-type PIV3 intranasally and intratracheally to two fully susceptible chimpanzees, respectively, and challenged the four primates with wild-type virus 1 month later. Compared with wild-type virus, which caused upper respiratory tract illness, the ca PIV3 was highly attenuated and manifested a 500-fold reduction in virus replication in both the upper and lower respiratory tracts of the two immunized animals. Despite restriction of virus replication, infection with ca PIV3 conferred a high level of protective immunity against challenge with wild-type virus. The ca PIV3 which had been passaged 12 times at 20-degrees-C did not retain its ts phenotype. These findings indicate that ca PIV3 may be a promising vaccine candidate for human beings if a passage level can be identified that is genetically stable, satisfactorily attenuated, and immunogenic. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV INFECT DIS,BALTIMORE,MD 21208. ST LOUIS UNIV,SCH MED,DEPT INTERNAL MED,DIV INFECT DIS,ST LOUIS,MO 63104. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,DEPT MICROBIOL,DIV MOLEC VIROL & IMMUNOL,ROCKVILLE,MD 20852. RP CLEMENTS, ML (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT INT HLTH,CTR IMMUNIZAT RES,BALTIMORE,MD 21208, USA. FU NIAID NIH HHS [N01 AI 52575, N01 AI 162515, N01 AI 05051] NR 48 TC 60 Z9 60 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 JUN PY 1991 VL 29 IS 6 BP 1175 EP 1182 PG 8 WC Microbiology SC Microbiology GA FM520 UT WOS:A1991FM52000016 PM 1650789 ER PT J AU LONGO, DL GLATSTEIN, E DUFFEY, PL YOUNG, RC HUBBARD, SM URBA, WJ WESLEY, MN RAUBITSCHEK, A JAFFE, ES WIERNIK, PH DEVITA, VT AF LONGO, DL GLATSTEIN, E DUFFEY, PL YOUNG, RC HUBBARD, SM URBA, WJ WESLEY, MN RAUBITSCHEK, A JAFFE, ES WIERNIK, PH DEVITA, VT TI RADIATION-THERAPY VERSUS COMBINATION CHEMOTHERAPY IN THE TREATMENT OF EARLY-STAGE HODGKINS-DISEASE - 7-YEAR RESULTS OF A PROSPECTIVE RANDOMIZED TRIAL SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FOLLOW-UP; SPLENECTOMY; RADIOTHERAPY; INFECTION; IIA; LEUKEMIA; RISK; MOPP; MANAGEMENT; PREVENTION C1 NCI,DIV CANC BIOL DIAG & CTR,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CO-74102] NR 40 TC 132 Z9 134 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 JUN PY 1991 VL 9 IS 6 BP 906 EP 917 PG 12 WC Oncology SC Oncology GA FP238 UT WOS:A1991FP23800004 PM 2033427 ER PT J AU MOORE, TD PHILLIPS, PH NERENSTONE, SR CHESON, BD AF MOORE, TD PHILLIPS, PH NERENSTONE, SR CHESON, BD TI SYSTEMIC TREATMENT OF ADVANCED AND RECURRENT ENDOMETRIAL CARCINOMA - CURRENT STATUS AND FUTURE-DIRECTIONS SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID GYNECOLOGIC-ONCOLOGY-GROUP; PHASE-II TRIAL; EPIDERMAL GROWTH-FACTOR; PROGESTERONE-RECEPTOR DISTRIBUTION; STEIN-LEVENTHAL SYNDROME; NUDE-MOUSE MODEL; MEDROXYPROGESTERONE ACETATE; HORMONAL-THERAPY; COMBINATION CHEMOTHERAPY; PERITONEAL CYTOLOGY C1 NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892. EMMES CORP,POTOMAC,MD. ONCOL ASSOCIATES PC,HARTFORD,CT. NR 161 TC 88 Z9 88 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 JUN PY 1991 VL 9 IS 6 BP 1071 EP 1088 PG 18 WC Oncology SC Oncology GA FP238 UT WOS:A1991FP23800024 PM 2033421 ER PT J AU KECK, PE CARTER, WP NIERENBERG, AA COOPER, TB POTTER, WZ ROTHSCHILD, AJ AF KECK, PE CARTER, WP NIERENBERG, AA COOPER, TB POTTER, WZ ROTHSCHILD, AJ TI ACUTE CARDIOVASCULAR EFFECTS OF TRANYLCYPROMINE - CORRELATION WITH PLASMA DRUG, METABOLITE, NOREPINEPHRINE, AND MHPG LEVELS SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID MONOAMINE-OXIDASE INHIBITORS; MAOI HYPERTENSIVE EPISODES; CEREBROSPINAL-FLUID; PHARMACOKINETICS; AMPHETAMINE; TRICYCLICS; URINE AB Background: Recent case reports, small series, and uncontrolled, unblinded studies have suggested that tranylcypromine may produce pressor reactions in some patients. However, the physiologic mechanism underlying this cardiovascular change is unknown. Method: The authors studied the acute cardiovascular effects of tranylcypromine in 13 patients and attempted to correlate these changes with plasma measures of parent drug, possible pressor metabolites, norepinephrine, and 3-methoxy-4-hydroxyphenylglycol. Results: Significant elevations in supine blood pressure occurred after administration of tranylcypromine and correlated with tranylcypromine dose. Similar changes were not observed in standing blood pressure measurements. In fact, an orthostatic decrease in blood pressure and increase in heart rate were observed. Amphetamine-like metabolites were not found. Conclusions: The authors speculate on possible mechanisms underlying these opposite cardiovascular effects. C1 MCLEAN HOSP,AFFECT DIS PROGRAM,BELMONT,MA 02178. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. NATHAN KUNE INST PSYCHIAT RES,ORANGEBURG,NY. COLUMBIA UNIV BARNARD COLL,NEW YORK PSYCHIAT INST,DEPT PSYCHIAT,NEW YORK,NY 10027. NIMH,CLIN PHARMACOL SECT,BETHESDA,MD 20892. NR 36 TC 17 Z9 17 U1 1 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUN PY 1991 VL 52 IS 6 BP 250 EP 254 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA FV580 UT WOS:A1991FV58000001 PM 2055897 ER PT J AU KETTER, TA POST, RM WORTHINGTON, K AF KETTER, TA POST, RM WORTHINGTON, K TI PRINCIPLES OF CLINICALLY IMPORTANT DRUG-INTERACTIONS WITH CARBAMAZEPINE .1. SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article C1 NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 0 TC 49 Z9 49 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD JUN PY 1991 VL 11 IS 3 BP 198 EP 203 PG 6 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA FN817 UT WOS:A1991FN81700009 PM 2066459 ER PT J AU PATO, MT MURPHY, DL DEVANE, CL AF PATO, MT MURPHY, DL DEVANE, CL TI SUSTAINED PLASMA-CONCENTRATIONS OF FLUOXETINE AND OR NORFLUOXETINE 4 AND 8 WEEKS AFTER FLUOXETINE DISCONTINUATION SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Letter ID CLINICAL-PHARMACOLOGY C1 UNIV FLORIDA,GAINESVILLE,FL 32611. RP PATO, MT (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 6 TC 95 Z9 95 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD JUN PY 1991 VL 11 IS 3 BP 224 EP 225 DI 10.1097/00004714-199106000-00024 PG 2 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA FN817 UT WOS:A1991FN81700016 PM 1741813 ER PT J AU KRIEGER, D SCLABASSI, RJ COPPOLA, R NAKAMURA, R AF KRIEGER, D SCLABASSI, RJ COPPOLA, R NAKAMURA, R TI SPATIOTEMPORAL CORTICAL PATTERNS EVOKED IN MONKEYS BY A DISCRIMINATION TASK SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID ASSOCIATION CORTEX; REACTION-TIME; HABITUATION; POTENTIALS AB The primary experimental objective of this work was to demonstrate localization and temporal sequencing of the functional steps carried out by nonhuman primate subjects during performance of a sensory discrimination task, i.e., to identify the locale and sequence of activation of regions that participate in sensory discrimination, stimulus classification, and response preparation. Multivariate statistical procedures were applied to evoked transcortical recordings to identify the location and order of occurrence of signals that are effective in discriminating task conditions and parameters. (1) Sensory discrimination, (2) stimulus classification, and (3) response preparation occurred in the expected sequence. Information that enabled discrimination using these procedures was distributed widely across the cortex; however, the maximum information content was localized to striate and prestriate cortex, anterior inferior parietal cortex, and temporal and premotor cortex, respectively. This work provides a perspective on brain mechanisms responsible for cognition and demonstrates a set of powerful multivariate analytic tools for functional mapping, i.e., identifying the location and sequencing of cognitive functions. C1 NIMH,BETHESDA,MD 20892. RP KRIEGER, D (reprint author), UNIV PITTSBURGH,CHILDRENS HOSP 3470,DEPT NEUROL SURG,3705 5TH AVE,PITTSBURGH,PA 15213, USA. NR 21 TC 3 Z9 3 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD ST JOURNALS DEPT, CAMBRIDGE, MA 02142 SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD SUM PY 1991 VL 3 IS 3 BP 242 EP 251 DI 10.1162/jocn.1991.3.3.242 PG 10 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA GB024 UT WOS:A1991GB02400004 PM 23964839 ER PT J AU INOUE, K NISHINO, T CREVELING, CR AF INOUE, K NISHINO, T CREVELING, CR TI IMMUNOCYTOCHEMICAL EVIDENCE FOR THE SITE OF O-METHYLATION IN RAT DENTAL-PULP SO JOURNAL OF DENTAL RESEARCH LA English DT Article ID INDIA INK PARTICLES; DEFENSE REACTION; LATEX BEADS; METHYLTRANSFERASE; FIBROBLASTS; LOCALIZATION; MICE AB Immunocytochemical observations by light and electron microscopy of catechol-O-methyltransferase (COMT) were conducted in dental pulp by use of a specific antibody to soluble rat-liver COMT and the peroxidase-antiperoxidase technique. Immunoreactive deposits were found in macrophages. The pattern of localization suggests that COMT may function in extraneuronal inactivation of catecholamines in dental pulp. C1 NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. RP INOUE, K (reprint author), OKAYAMA UNIV,SCH DENT,DEPT ORAL ANAT,OKAYAMA 700,JAPAN. NR 20 TC 4 Z9 4 U1 1 U2 1 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JUN PY 1991 VL 70 IS 6 BP 966 EP 969 DI 10.1177/00220345910700061101 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA FR234 UT WOS:A1991FR23400006 PM 2045576 ER PT J AU DELIBERO, G CASORATI, G GIACHINO, C CARBONARA, C MIGONE, N MATZINGER, P LANZAVECCHIA, A AF DELIBERO, G CASORATI, G GIACHINO, C CARBONARA, C MIGONE, N MATZINGER, P LANZAVECCHIA, A TI SELECTION BY 2 POWERFUL ANTIGENS MAY ACCOUNT FOR THE PRESENCE OF THE MAJOR POPULATION OF HUMAN PERIPHERAL GAMMA DELTA T-CELLS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CYTOLYTIC LYMPHOCYTES-T; HEAT-SHOCK PROTEIN; MYCOBACTERIUM-TUBERCULOSIS; RECEPTOR REPERTOIRE; NATURAL-KILLER; GENE ENCODES; RECOGNITION; CLONES; FORMS; BLOOD AB V-gamma-9/V-delta-2 cells represent a fraction of human-gamma/delta-cells that is expanded after birth in the periphery, carries markers of activated cells, and becomes a major population in peripheral blood. We found that these cells do not comprise a single population but actually represent two nested sets, the smaller of which, specific for Mycobacterium tuberculosis-pulsed antigen-presenting cells (APC), is contained in a larger set specific for an antigen found on the Molt-4 lymphoma. The larger set, representing 40-80% of all blood-gamma/delta-cells, is comprised of cells bearing the V-gamma-9/C-gamma-1 chain. Cells in the smaller, included set have an additional requirement for V-delta-2(and probably for certain permissive junctional regions, since a very small percentage of V-gamma-9/V-delta-2 cells do not react against mycobacteria-pulsed APC). Optimal stimulation by mycobacteria is dependent on the presence of APC, and is not restricted by classical major histocompatibility complex molecules. Some of the V-gamma-9/V-delta-2 mycobacteria-specific clones are also stimulated by APC pulsed with different bacteria, such as Listeria monocytogenes and Escherichia coli, indicatingthat the population includes several different patterns of reactivity. These data establish a relationship in humans between specificity and V-gamma/V-delta-gene usage, and offer an explanation for the peripheral expansion of these gamma/delta-cells. C1 CNR,I-10126 TURIN,ITALY. UNIV TURIN,DIPARTIMENTO GENET BIOL & CHIM MED,I-10126 TURIN,ITALY. UNIV HOSP BASEL,DEPT RES,CH-4031 BASEL,SWITZERLAND. NIH,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892. RP DELIBERO, G (reprint author), UNIV HOSP BASEL,BASEL INST IMMUNOL,CH-4031 BASEL,SWITZERLAND. NR 46 TC 209 Z9 209 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 1 PY 1991 VL 173 IS 6 BP 1311 EP 1322 DI 10.1084/jem.173.6.1311 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA FN859 UT WOS:A1991FN85900003 PM 1827824 ER PT J AU ROSENBERG, AS MUNITZ, TI MANIERO, TG SINGER, A AF ROSENBERG, AS MUNITZ, TI MANIERO, TG SINGER, A TI CELLULAR BASIS OF SKIN ALLOGRAFT-REJECTION ACROSS A CLASS-I MAJOR HISTOCOMPATIBILITY BARRIER IN MICE DEPLETED OF CD8+ T-CELLS INVIVO SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID EPIDERMAL LANGERHANS CELLS; MULTIVALENT CROSS-LINKING; LYMPHOCYTES-T; DENDRITIC CELLS; PRECURSOR CELLS; SUBSETS; EXPRESSION; RESPONSES; MOLECULES; ANTIGENS AB The present study was undertaken to define the cellular mechanisms involved in the rejection of major histocompatibility complex (MHC) class I disparate skin grafts by mice depleted of CD8+ T cells in vivo. Mice were effectively depleted of CD8+ T cells by adult thymectomy followed by in vivo administration of anti-CD8 monoclonal antibody (mAb) and then engrafted with allogeneic skin. We found that CD8 depleted mice did reject MHC class I disparate skin grafts, but only when the grafts also expressed additional alloantigens. Despite the marked depletion of CD8+ T cells in these mice, we found that their rejection of MHC class I disparate grafts was mediated by CD8+ cytolytic T lymphocyte (CTL) effectors that had escaped depletion. These CD8+ CTL effectors were unique in that: (a) their generation was dependent upon the injected anti-CD8 mAb and upon exposure to class I MHC alloantigens expressed on the engrafted skin, and (b) their effector function was resistant to blockade by anti-CD8 mAb. We observed that the additional alloantigens coexpressed on MHC class I disparate grafts that triggered graft rejection in CD8-depleted mice could be MHC-linked or not and that they functioned in these rejection responses to activate third party specific CD4+ T helper (Th) cells to provide helper signals for the generation of CD8+ anti-CD8 resistant CTL effector cells. Thus, mice depleted of CD8+ T cells by thymectomy and in vivo administration of anti-CD8 mAb harbor a unique population of anti-CD8 resistant, CD8+ effector cells that mediate anti-MHC class I responses in vivo and in vitro, but require help from third party specific Th cells to do so. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RP ROSENBERG, AS (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892, USA. NR 30 TC 75 Z9 75 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 1 PY 1991 VL 173 IS 6 BP 1463 EP 1471 DI 10.1084/jem.173.6.1463 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA FN859 UT WOS:A1991FN85900017 PM 1674524 ER PT J AU INOUE, K CREVELING, CR AF INOUE, K CREVELING, CR TI INDUCTION OF CATECHOL-O-METHYLTRANSFERASE IN THE LUMINAL EPITHELIUM OF RAT UTERUS BY PROGESTERONE SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE PROGESTERONE; RAT; UTERUS; LUMINAL EPITHELIUM; PSEUDOPREGNANCY; IMMUNOCYTOCHEMISTRY; PEROXIDASE; DIAMINOBENZIDINE; CATECHOL-O-METHYLTRANSFERASE; STREPTAVIDIN ID METABOLISM; ESTRADIOL AB We performed light microscopic immunocytochemical observations of the localization of catechol-O-methyltransferase (COMT) in rat uterus, using a rabbit anti-rat serum specific for the soluble form of rat liver COMT, biotinylated goat anti-rabbit immunoglobulin, and peroxidase conjugated with streptavidin. In the non-pregnant rat, COMT was minimal but detectable in the uterine luminal and glandular epithelium, with greater amounts present in uteri from rats in estrus than those in diestrus. In early pregnancy a robust accumulation of COMT was observed in the luminal epithelium. To more precisely define both the timing and the factors contributing to the appearance of COMT, uteri were examined on Days 1-5 in pregnant and pseudopregnant rats. Accumulation of COMT in the luminal epithelium was observed by Day 3 in uteri from pregnant and pseudopregnant rats and by Day 4 in lactating post-partum rats. No immunostaining of COMT was observed in uteri from non-lactating post-partum rats. Ovariectomy on Day 0 or 1 but not on Day 2 of pregnancy prevented the appearance of COMT on Day 4. Progesterone treatment immediately after ovariectomy on Day 0 or 1 of pregnancy restored the COMT. C1 NIDDK,BIOORGAN CHEM LAB,BLDG 8A,ROOM 1A-27,BETHESDA,MD 20892. OKAYAMA UNIV,SCH DENT,DEPT ORAL ANAT,OKAYAMA 700,JAPAN. NR 34 TC 10 Z9 10 U1 0 U2 2 PU HISTOCHEMICAL SOC INC PI NEW YORK PA MT SINAI MEDICAL CENTER 19 EAST 98TH ST SUTIE 9G, NEW YORK, NY 10029 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD JUN PY 1991 VL 39 IS 6 BP 823 EP 828 PG 6 WC Cell Biology SC Cell Biology GA FM061 UT WOS:A1991FM06100010 PM 2033240 ER PT J AU COOPER, HL FULDNER, R MCDUFFIE, E BRAVERMAN, R AF COOPER, HL FULDNER, R MCDUFFIE, E BRAVERMAN, R TI T-CELL RECEPTOR ACTIVATION INDUCES RAPID PHOSPHORYLATION OF PROSOLIN, WHICH MEDIATES DOWN-REGULATION OF DNA-SYNTHESIS IN PROLIFERATING PERIPHERAL LYMPHOCYTES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DEPENDENT PROTEIN-KINASE; PROMYELOCYTIC LEUKEMIA-CELLS; PHORBOL ESTERS; ANTIGEN RECEPTOR; C ACTIVATION; CALCIUM; INDUCTION; CLONES; DIFFERENTIATION; FRAGMENTATION AB Prosolin is a major cytosolic phosphoprotein expressed prominently in rapidly proliferating human peripheral lymphocytes but produced at very low levels in resting (G(O)) PBL. It undergoes rapid phosphorylation upon treatment of growing cells with tumor-producing phorbol esters (TPA) and this phosphorylation event is correlated with a rapid down-regulation of DNA synthesis. In the present report we have studied various agents that, like TPA, act as partial or complete mitogens for G(O) PBL and have determined their effect on phosphorylation of prosolin and on DNA synthesis in rapidly proliferating (IL-2-dependent) human PBL. Agents that activate the TCR (OKT3 and PHA), as well as agents that by-pass the receptor but activate biochemical pathways associated with TCR activation (TPA and Ca2+-ionophore), all produced rapid phosphorylation of prosolin and prompt down-regulation of DNA synthesis. Four phosphorylated forms of prosolin were produced, indicating activation of a complex phosphorylation pathway. Down-regulation of DNA synthesis did not lead to cell death or to permanent arrest, but was reversed after 24 to 48 h, and was not associated with any reduction in overall protein synthesis. Agents that bind to determinants closely connected to the TCR but without activating it (OKT4 and OKT8) had no effect on either prosolin phosphorylation or DNA synthesis. The results indicate that prosolin is an early target of the protein kinase activities induced by activation of the TCR in proliferating PBL, and suggest that its phosphorylation mediates the TCR signal, transmitting it into a biochemical pathway leading specifically to down-regulation of DNA synthesis. In G(O) PBL, in which the negligible expression of prosolin precludes significant production of phosphorylated species, this inhibitory pathway is effectively blocked. RP COOPER, HL (reprint author), NCI,TUMOR IMMUNOL & BIOL LAB,CELL & MOLEC PHYSIOL SECT,BETHESDA,MD 20892, USA. NR 46 TC 42 Z9 42 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 JUN 1 PY 1991 VL 146 IS 11 BP 3689 EP 3696 PG 8 WC Immunology SC Immunology GA FN054 UT WOS:A1991FN05400001 PM 1903411 ER PT J AU OHNO, H USHIYAMA, C TANIGUCHI, M GERMAIN, RN SAITO, T AF OHNO, H USHIYAMA, C TANIGUCHI, M GERMAIN, RN SAITO, T TI CD2 CAN MEDIATE TCR/CD3-INDEPENDENT T-CELL ACTIVATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN LYMPHOCYTES-T; ANTIGEN RECEPTOR; MONOCLONAL-ANTIBODIES; CO-EXPRESSION; COMPLEX; MOLECULES; SURFACE; T11; REQUIRES; PATHWAYS AB T lymphocytes can be activated clonotypically through TCR/CD3 complex or polyclonally via the CD2 molecule. Whether CD2-mediated activation is dependent on TCR/CD3 expression or signaling is controversial. We have re-explored this issue by using a series of CD2-transfected, TCR/CD3 surface membrane-negative human and mouse T cells. Our results clearly show that such T cells can be triggered for IL-2 secretion and increases in intracellular Ca2+ through the CD2 molecule in the absence of surface expression of TCR/CD3 complexes. These responses are only observed when cells express high levels of CD2 and there is a critical threshold of CD2 expression necessary for such activation in the absence of CD3. Concomitant expression of TCR/CD3 complex markedly lowers the level of CD2 required for activation via the latter pathway. These results provide a clear resolution of the controversy concerning the requirement for surface CD3 expression in T cell activation through CD2 and further suggest a possible role for CD2 in activation of TCR/CD3-negative cells. C1 CHIBA UNIV,SCH MED,CTR NEUROBIOL & IMMUNOL,DIV MOLEC GENET,1-8-1 INOHANA,CHIBA 280,JAPAN. NIAID,IMMUNOL LAB,BETHESDA,MD 20982. RI Saito, Takashi/C-9684-2009; Ohno, Hiroshi/L-7899-2014; Taniguchi, Masaru/N-7932-2015 OI Saito, Takashi/0000-0001-9495-3547; Ohno, Hiroshi/0000-0001-8776-9661; Taniguchi, Masaru/0000-0001-7821-7179 NR 24 TC 46 Z9 46 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 JUN 1 PY 1991 VL 146 IS 11 BP 3742 EP 3746 PG 5 WC Immunology SC Immunology GA FN054 UT WOS:A1991FN05400009 PM 1674520 ER PT J AU LIPHAM, WJ REDMOND, TM TAKAHASHI, H BERZOFSKY, JA WIGGERT, B CHADER, GJ GERY, I AF LIPHAM, WJ REDMOND, TM TAKAHASHI, H BERZOFSKY, JA WIGGERT, B CHADER, GJ GERY, I TI RECOGNITION OF PEPTIDES THAT ARE IMMUNOPATHOGENIC BUT CRYPTIC - MECHANISMS THAT ALLOW LYMPHOCYTES SENSITIZED AGAINST CRYPTIC PEPTIDES TO INITIATE PATHOGENIC AUTOIMMUNE PROCESSES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RETINOID-BINDING-PROTEIN; ANTIGEN PRESENTATION; S-ANTIGEN; IRBP; DETERMINANT; IMMUNODOMINANT; UVEORETINITIS; PINEALITIS; REQUIREMENTS; INDUCTION AB Interphotoreceptor retinoid binding protein (IRBP) is a glycoprotein that localizes in the retina and induces inflammatory changes in this tissue in immunized animals. Certain IRBP-derived peptide determinants are also immunopathogenic, and we have previously shown that these determinants could be either immunodominant or cryptic. Lymphocytes sensitized against the cryptic peptides do not recognize whole IRBP in vitro, and yet these lymphocytes must recognize the protein in vivo to initiate the autoimmune pathogenic process. We have examined here two hypothetical explanations for this dissociation: 1) It is possible that when IRBP is processed in vitro, immunodominant peptide determinants compete with the cryptic ones and inhibit their interaction with the MHC molecules on the APC. This explanation was ruled out here by the finding that the immunodominant peptide 1179-1191 ("W10") did not inhibit the response to a cryptic one, 1158-1180 ("R4"), when added at equivalent and even moderately higher concentrations. 2) The second hypothesis proposes that the cryptic antigenic sites are not generated from IRBP by the APC in vitro, whereas enzymes in the retina digest the protein to yield fragments that generate these antigenic sites upon processing by the APC. In line with this hypothesis, we have found that cleavage of IRBP by certain endoproteinases (Asp-N, Glu-C, or V-8) produced molecules that were recognized in culture by lymphocytes sensitized to the immunopathogenic but cryptic peptide R4. This study, therefore, describes a putative Ag processing mechanism that results in IRBP recognition and, consequently, the initiation of an autoimmune process by lymphocytes sensitized against a cryptic peptide. Furthermore, experiments with R4 and other cryptic peptides have shown that cleavage fragments of up to 38 residues in length can be presented by APC, to stimulate lymphocytes sensitized against these peptides. No responses were stimulated, however, by fragments of 75 or more residues. The data thus provide new insights into the processing and presentation of cryptic peptide determinants by APC. C1 NEI,IMMUNOL LAB,BLDG 10,ROOM 10N208,BETHESDA,MD 20892. NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,METAB BRANCH,BETHESDA,MD 20892. NIH,HOWARD HUGHES MED INST,RES SCHOLARS PROGRAM,BETHESDA,MD 20892. OI Redmond, T. Michael/0000-0002-1813-5291 NR 30 TC 75 Z9 75 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 JUN 1 PY 1991 VL 146 IS 11 BP 3757 EP 3762 PG 6 WC Immunology SC Immunology GA FN054 UT WOS:A1991FN05400012 PM 1709661 ER PT J AU ORTALDO, JR MASON, AT OSHEA, JJ SMYTH, MJ FALK, LA KENNEDY, ICS LONGO, DL RUSCETTI, FW AF ORTALDO, JR MASON, AT OSHEA, JJ SMYTH, MJ FALK, LA KENNEDY, ICS LONGO, DL RUSCETTI, FW TI MECHANISTIC STUDIES OF TRANSFORMING GROWTH-FACTOR-BETA INHIBITION OF IL-2-DEPENDENT ACTIVATION OF CD3- LARGE ANTIGRANULOCYTES LYMPHOCYTE FUNCTIONS - REGULATION OF IL-2R-BETA (P75) SIGNAL TRANSDUCTION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER CELLS; TYROSINE KINASE-ACTIVITY; NECROSIS FACTOR-ALPHA; INTERLEUKIN-2 RECEPTOR; IL-2 RECEPTOR; RECOMBINANT INTERLEUKIN-2; GAMMA PRODUCTION; GENE-EXPRESSION; T-CELLS; INDUCTION AB CD3- large granular lymphocyte (LGL) express constitutive levels of functional IL-2R-beta. TGF-beta inhibited several IL-2R-beta-mediated events in LGL, including IL-2-induced NK and lymphokine-activating factor activities, IFN-gamma gene expression and secretion, and IL-2R-alpha expression. TGF-beta inhibited these IL-2-induced LGL functions in a dose-dependent and reversible manner. By contrast, TGF-beta had little effect on LGL IL-2R-beta expression and TGF-beta receptors were not induced by IL-2. Studies were performed to examine binding and internalization of radiolabeled IL-2. These experiments demonstrated that the rapid binding and internalization of [I-125]IL-2 was not altered in CD3-LGL pretreated with TGF-beta. These internalization studies indicated that the TGF-beta inhibition represented postreceptor-binding events in NK cells. Further studies were initiated to examine signaling events in CD3-LGL. When IL-2-induced tyrosine phosphorylation events were examined, significant inhibition was seen of selected phosphoproteins in TGF-beta-pretreated cells. In addition, the ability of TGF-beta to also inhibit IL-2 induction of LGL IL-2R-alpha and IFN-gamma mRNA expression was consistent with the hypothesis that posttranscriptional mechanisms were unlikely to be affected by TGF-beta. Collectively, these data indicated that TGF-beta inhibited IL-2-induced CD3- LGL functions and suggested that TGF-beta inhibition occurs either at the level of specific tyrosine phosphorylation and/or IL-2-induced transcriptional control factors. C1 NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,OFF ASSOCIATE DIRECTOR,FREDERICK,MD 21702. RP ORTALDO, JR (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,BLDG 560,FREDERICK,MD 21702, USA. RI Smyth, Mark/H-8709-2014 OI Smyth, Mark/0000-0001-7098-7240 NR 34 TC 81 Z9 84 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 JUN 1 PY 1991 VL 146 IS 11 BP 3791 EP 3798 PG 8 WC Immunology SC Immunology GA FN054 UT WOS:A1991FN05400017 PM 1851793 ER PT J AU SMYTH, MJ ZACHARIAE, COC NORIHISA, Y ORTALDO, JR HISHINUMA, A MATSUSHIMA, K AF SMYTH, MJ ZACHARIAE, COC NORIHISA, Y ORTALDO, JR HISHINUMA, A MATSUSHIMA, K TI IL-8 GENE-EXPRESSION AND PRODUCTION IN HUMAN PERIPHERAL-BLOOD LYMPHOCYTE SUBSETS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER CELLS; NEUTROPHIL CHEMOTACTIC FACTOR; LARGE GRANULAR LYMPHOCYTES; TUMOR NECROSIS FACTOR; INTERLEUKIN-2 RECEPTOR; MOLECULAR-CLONING; COMPLEMENTARY-DNA; GAMMA PRODUCTION; MESSENGER-RNA; GROWTH-FACTOR AB We have investigated IL-8 mRNA expression and IL-8 production in highly purified subsets of peripheral blood lymphocytes. T cells stimulated with PHA, ionomycin, or PMA alone failed to express IL-8 mRNA. However T cells stimulated with a combination of PMA and ionomycin or PMA and PHA expressed IL-8 mRNA in a PMA dose-dependent manner and maximally after 3 to 6 h of culture. Induction of IL-8 mRNA appeared to be specifically in the CD4+ T cell subset. Surprisingly, however, T cells were not induced to secrete significant levels of IL-8 polypeptide, even in the presence of accessory monocytes. In addition, immunoprecipitation analysis of PMA/ionomycin-treated T cell lysates detected only minor levels of cellular IL-8 Ag thereby suggesting that in T cells, the production of IL-8 was inhibited at the posttranscriptional level. By contrast, CD3- large granular lymphocytes (LGL) were both induced to express IL-8 mRNA and secrete biologically active IL-8 upon specific stimulation with IL-2 and ligand (anti-CD16 mAb) for the NK cell receptor for IgG-Fc (CD16), or upon nonspecific stimulation with PMA. IL-2 and anti-CD16 mAb synergistically induced IL-8 expression in LGL. Other nonactivating LGL-specific mAb did not induce LGL IL-8 secretion. The amount of IL-8 produced by activated LGL was donor variable, but generally 5 to 10 times less than that secreted by monocytes. The ability of LGL to release IL-8 and a large number of other cytokines further supports the hypothesis that LGL may contribute to both inflammatory and immunologic responses. C1 NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. RP SMYTH, MJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,BLDG 560,RM 31-16,FREDERICK,MD 21702, USA. RI Smyth, Mark/H-8709-2014 OI Smyth, Mark/0000-0001-7098-7240 NR 51 TC 91 Z9 91 U1 1 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 JUN 1 PY 1991 VL 146 IS 11 BP 3815 EP 3823 PG 9 WC Immunology SC Immunology GA FN054 UT WOS:A1991FN05400020 PM 1827816 ER PT J AU TANAKA, T BENSASSON, SZ PAUL, WE AF TANAKA, T BENSASSON, SZ PAUL, WE TI IL-4 INCREASES IL-2 PRODUCTION BY T-CELLS IN RESPONSE TO ACCESSORY CELL-INDEPENDENT STIMULI SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RESTING LYMPHOCYTES-T; FACTOR-I; MESSENGER-RNA; MONOCLONAL-ANTIBODIES; INTERLEUKIN-4; ACTIVATION; PROLIFERATION; INVITRO; CULTURE; ABSENCE AB Freshly prepared, highly purified T cells from naive mice failed to produce IL-2 in response to soluble anti-CD3 antibody or to Con A and produced only small amounts of IL-2 in response to anti-CD3 coated on the surface of microwells. IL-2 production in response to soluble anti-CD3 or to Con A required the addition of accessory cells. By contrast, the addition of IL-4 strikingly enhanced the production of IL-2 by plate-bound anti-CD3-stimulated T cells in the absence or the presence of added accessory cells. Furthermore, anti-IL-4 mAb inhibited IL-2 production by anti-CD3-stimulated T cells, which indicates that endogenously produced IL-4 was important in IL-2 production by T cells to plate-bound anti-CD3. The capacity of IL-4 to enhance and of anti-IL-4 to inhibit IL-2 production in response to plate-bound anti-CD3 was also observed with both unstimulated T cells and with T cells that had been previously stimulated with anti-CD3 antibody. When activated T cells were restimulated with anti-CD3, the effect of IL-4 in enhancing IL-2 production was detectable within 6 to 8 h after restimulation. The effect of IL-4 on IL-2 production was not due to prolongation of survival or to enhanced proliferation of T cells. Northern blot analysis showed that T cells treated with anti-CD3 plus IL-4 had more than 10-fold more IL-2 mRNA than did T cells treated with anti-CD3 plus anti-IL-4; this was observed within 6 h of stimulation under certain circumstances. The increased level of IL-2 mRNA by IL-4 was achieved without any change in message half-life, suggesting that IL-4 enhances transcriptional activation of the IL-2 gene in such cells. These results lead to the conclusion that IL-4 has a critical role in IL-2 production in response to accessory cell-independent stimuli (plate-bound anti-CD3 anti-body), although it is not essential to IL-2 production in response to accessory cell-dependent stimuli (soluble anti-CD3 and Con A). C1 NIAID,IMMUNOL LAB,BLDG 10,RM 11N311,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,HADASSAH MED CTR,LAUTENBERG CTR TUMOR IMMUNOL,JERUSALEM,ISRAEL. NR 36 TC 20 Z9 20 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 JUN 1 PY 1991 VL 146 IS 11 BP 3831 EP 3839 PG 9 WC Immunology SC Immunology GA FN054 UT WOS:A1991FN05400022 PM 1827817 ER PT J AU ISHIHARA, C MIYAZAWA, M NISHIO, J CHESEBRO, B AF ISHIHARA, C MIYAZAWA, M NISHIO, J CHESEBRO, B TI INDUCTION OF PROTECTIVE IMMUNITY TO FRIEND MURINE LEUKEMIA-VIRUS IN GENETIC NONRESPONDERS TO VIRUS ENVELOPE PROTEIN SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOXIC LYMPHOCYTES-T; CIRCUMSPOROZOITE PROTEIN; PLASMODIUM-FALCIPARUM; INFLUENZA-VIRUS; RETROVIRUS; ANTIBODIES; RECOVERY; EPITOPE; ANTIGENS; MICE AB (B10.A x A/WySn)F1, H-2a/a, mice are genetic nonresponders to the envelope protein of Friend murine leukemia helper virus (F-MuLV) when immunized with a recombinant vaccinia virus expressing F-MuLV env gene. In contrast these mice can be protectively immunized against leukemogenic Friend virus complex using formalin-fixed F-MuLV virions in CFA. To determine which viral proteins were responsible for this immune protection, virion proteins prepared by SDS-PAGE and electroelution were used to immunize mice. Purified gp70 envelope protein in CFA was capable of inducing strong immune protection against the challenge with Friend virus complex in H-2a/a mice. Immunologic studies demonstrated that immunized mice developed a virus-specific T cell proliferative response and showed IgM to IgG Ig class switching of virus-neutralizing antibodies. These results indicated that genetically controlled immune nonresponsiveness to F-MuLV envelope Ag in H-2a/a mice could be overcome using denatured viral envelope protein together with a strong adjuvant. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. NR 34 TC 18 Z9 18 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 JUN 1 PY 1991 VL 146 IS 11 BP 3958 EP 3963 PG 6 WC Immunology SC Immunology GA FN054 UT WOS:A1991FN05400039 PM 2033265 ER PT J AU KEHRL, JH THEVENIN, C RIECKMANN, P FAUCI, AS AF KEHRL, JH THEVENIN, C RIECKMANN, P FAUCI, AS TI TRANSFORMING GROWTH-FACTOR-BETA SUPPRESSES HUMAN LYMPHOCYTE-B IG PRODUCTION BY INHIBITING SYNTHESIS AND THE SWITCH FROM THE MEMBRANE FORM TO THE SECRETED FORM OF IG MESSENGER-RNA SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR NECROSIS FACTOR; NF-KAPPA-B; CELL-SPECIFIC ENHANCER; OCTAMER DNA MOTIF; FACTOR-ALPHA; NUCLEAR FACTOR; IMMUNOGLOBULIN GENES; CONSERVED SEQUENCE; 3' ENDS; C-FOS AB Transforming growth factor-beta (TGF-beta) inhibits B cell Ig secretion and reduces B cell membrane Ig expression. The addition of TGF-beta to human B lymphocyte cultures stimulated with Staphylococcus aureus Cowan strain I and IL-2 completely inhibited B cell Ig secretion (> 90%) and decreased B cell surface IgM, IgD, kappa-L chain, and lambda-L chain expression. In contrast, TGF-beta had only minimal effects on two other B cell membrane proteins, HLA-DR and CD20. Internal labeling with [S-35]methionine and immunoprecipitation with anti-IgM, anti-kappa, and anti-lambda antibodies revealed a striking reduction in kappa-L chain in the presence of TGF-beta. A less pronounced reduction in lambda-L chain and mu-H chain was also noted. Northern blot analysis of RNA purified from B cells treated with TGF-beta for varying time intervals revealed a significant decrease in steady state-kappa and lambda-L chain mRNA levels. Furthermore, a significant decrease in the switch from the membrane forms of mu and gamma to their respective secreted forms was noted in the presence of TGF-beta. Nuclear run-on experiments demonstrated decreased transcription of kappa-L chain. The effects of TGF-beta on two transcriptional regulatory factors, Oct-2 and nuclear factor (NF) kappa-B, known to be important in Ig gene transcription were examined. Oct-2 mRNA levels and both Oct-2 and NF-kappa-B proteins in nuclear extracts were not altered by treatment with TGF-beta. In contrast, levels of the transcriptional factor AP-1, which is not known to be important in B cell Ig production, were reduced by TGF-beta. These findings demonstrate that TGF-beta decreases B lymphocyte Ig secretion by inhibiting the synthesis of Ig mRNA and inhibiting the switch from the membrane form to the secreted forms of mu and gamma-mRNA. The mechanism by which TGF-beta inhibits Ig chain synthesis is unclear although it does not involve inhibition of the binding of NF-kappa-B or Oct-2 to their respective target sequences. RP KEHRL, JH (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 11B-13,BETHESDA,MD 20892, USA. OI Kehrl, John/0000-0002-6526-159X NR 53 TC 102 Z9 105 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 JUN 1 PY 1991 VL 146 IS 11 BP 4016 EP 4023 PG 8 WC Immunology SC Immunology GA FN054 UT WOS:A1991FN05400047 PM 1903417 ER PT J AU INVERARDI, L WITSON, JC FUAD, SA WINKLERPICKETT, RT ORTALDO, JR BACH, FH AF INVERARDI, L WITSON, JC FUAD, SA WINKLERPICKETT, RT ORTALDO, JR BACH, FH TI CD3 NEGATIVE SMALL AGRANULAR LYMPHOCYTES ARE NATURAL-KILLER-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LEUCINE-METHYL-ESTER; LARGE GRANULAR LYMPHOCYTES; LYSOSOMOTROPIC AGENT; MONOCLONAL-ANTIBODIES; T-CELL; GENERATION; ANTIGENS; CULTURE AB We describe here that CD3-, CD16+ and/or CD56+ small lymphocytes, in a highly reproducible fashion, mediate a significant level of K562 killing that is, on a "per cell" basis, comparable to the cytolytic activity of CD3- LGL. The CD3- small lymphocytes appeared to have no granules based on light and electron microscopy and lack of right-angle scatter on the FACS; we thus refer to them as small "agranular" lymphocytes (SAL). The lytic activity against K562 is inhibited by treatment with either L-leucine methyl ester or EGTA, which are reported to effect granule-dependent killing. We suggest that the SAL have lytic molecules in their cytoplasm (which are sensitive to these treatments) but that these molecules are not organized into discrete granules as found in LGL. The CD3- SAL are phenotypically very similar to LGL and both SAL and LGL mediated equal and reproducible antibody-dependent cell-mediated cytotoxicity. These observations force redefinition of the concept of NK cells to include both CD3- LGL and CD3- SAL. C1 UNIV MINNESOTA,IMMUNOBIOL RES CTR,DEPT LAB MED PATHOL,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,DEPT SURG,MINNEAPOLIS,MN 55455. NCI,FREDERICK CANC RES FDN,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. FU NIADDK NIH HHS [AM 13083]; NIAID NIH HHS [AI 17687, AI 19007] NR 17 TC 21 Z9 21 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 JUN 1 PY 1991 VL 146 IS 11 BP 4048 EP 4052 PG 5 WC Immunology SC Immunology GA FN054 UT WOS:A1991FN05400051 PM 1827820 ER PT J AU HOM, SS TOPALIAN, SL SIMONIS, T MANCINI, M ROSENBERG, SA AF HOM, SS TOPALIAN, SL SIMONIS, T MANCINI, M ROSENBERG, SA TI COMMON EXPRESSION OF MELANOMA TUMOR-ASSOCIATED ANTIGENS RECOGNIZED BY HUMAN TUMOR INFILTRATING LYMPHOCYTES - ANALYSIS BY HUMAN LYMPHOCYTE ANTIGEN RESTRICTION SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE IMMUNOTHERAPY; MELANOMA; MAJOR HISTOCOMPATIBILITY COMPLEX RESTRICTION; TUMOR ANTIGEN; TUMOR INFILTRATING LYMPHOCYTES ID CLASS-I ANTIGENS; T-CELL CLONES; HLA-A; HISTOCOMPATIBILITY ANTIGENS; ALIEN ANTIGENS; MESSENGER-RNA; CANCER; IMMUNOTHERAPY; LINES AB Major histocompatibility complex (MHC) class I antigens (Ag), particularly human lymphocyte antigen (HLA)-A2, have been shown to function as restriction elements in human cytotoxic T lymphocyte recognition of tumor. This study was undertaken to determine the function of non-A2 MHC class I Ag in tumor recognition by tumor-infiltrating lymphocytes (TILs) cultured from six melanomas, and to find evidence for shared or unique tumor-associated Ag. Four predominantly CD8+ and two mixed CD4+, CD8+ population TIL cultures were tested for lysis in short-term Cr-51-release assays against a panel of targets including 29 fresh melanomas, 2 fresh sarcomas, 11 cultured melanoma lines, and 14 nonmelanoma cell lines derived from HLA-typed patients. All six melanoma TILs lysed the autologous melanoma. Two of three TILs from HLA-A2+ patients lysed allogeneic melanomas matched for HLA-A2, giving evidence for shared tumor Ag; one of these TILs also used HLA-B44 as a restriction element. The third HLA-A2+ TIL lysed autologous melanoma but not autologous Epstein-Barr virus-transformed B cells nor 14 HLA-A2 matched allogeneic melanomas, suggesting the possibility of a unique tumor Ag in this system. The three HLA-A2- TILs each lysed multiple HLA-matched melanomas, using HLA-A24, HLA-A31, and HLA-Cw7 as restriction elements. Blocking of autologous and allogeneic melanoma lysis by TILs with mAb w6/32 (anti-MHC class I) and anti-CD3, as well as cold target inhibition assays, confirmed that specific interaction of the T-cell receptor with MHC class I Ag and the relevant tumor Ag on the target cell surface is required for tumor lysis. These data provide evidence for specific recognition of shared melanoma Ag by human TILs. C1 NIH,CTR CLIN,DEPT TRANSFUS MED,HUMAN LYMPHOCYTE ANTIGEN LAB,BETHESDA,MD 20892. RP HOM, SS (reprint author), NCI,SURG BRANCH,DIV CANC TREATMENT,BLDG 10,ROOM 2B42,BETHESDA,MD 20892, USA. NR 20 TC 96 Z9 96 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 JUN PY 1991 VL 10 IS 3 BP 153 EP 164 PG 12 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA FM895 UT WOS:A1991FM89500001 PM 1868040 ER PT J AU FRUEHAUF, JP MIMNAUGH, EG SINHA, BK AF FRUEHAUF, JP MIMNAUGH, EG SINHA, BK TI DOXORUBICIN-INDUCED CROSS-RESISTANCE TO TUMOR-NECROSIS-FACTOR (TNF) RELATED TO DIFFERENTIAL TNF PROCESSING SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE TUMOR NECROSIS FACTOR; DRUG RESISTANCE; RECEPTOR PROCESSING ID INVITRO CYTO-TOXICITY; DNA TOPOISOMERASE-II; BREAST-CANCER-CELLS; GROWTH-FACTOR-BETA; FACTOR-ALPHA; FACTOR RECEPTOR; PHASE-I; MOLECULAR-CLONING; GAMMA-INTERFERON; BINDING AB To evaluate whether cells selected for doxorubicin resistance were cross-resistant to tumor necrosis factor, the effects of doxorubicin and recombinant human tumor necrosis factor-alpha (TNF) on doxorubicin-sensitive (WT) and 40-fold doxorubicin-resistant (40F) MCF-7 cell proliferation were assessed. The median dose (MD) for doxorubicin was 14.5 nM for WT cells and 474 nM for 40F cells. The MD for TNF was 0.18 nM for WT cells, while 40F cells were highly resistant to TNF concentrations up to 60 nM. Doxorubicin and TNF in combination were synergistic against WT cells, but not 40F cells. Glutathione depletion by buthionine sulfoxamine sensitized WT cells threefold to TNF, with no change in their response to doxorubicin, while 40F cells showed a twofold increase in doxorubicin sensitivity, with no apparent change in their resistance to TNF. No significant differences in TNF receptor number, K(d), or capacity for TNF internalization were noted between the two cell types. WT cells produced a single 15 kDa TNF degradation product, while the 40F cells produced three lower molecular weight degradation products. We conclude that cross-resistance to TNF in doxorubicin-resistant MCF-7 cells may be explained in part by altered TNF degradation. RP FRUEHAUF, JP (reprint author), NCI,CLIN PHARMACOL BRANCH,BIOCHEM & MOLEC PHARMACOL SECT,BLDG 10,ROOM 6N-113,BETHESDA,MD 20892, USA. NR 56 TC 16 Z9 16 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 JUN PY 1991 VL 10 IS 3 BP 165 EP 173 DI 10.1097/00002371-199106000-00002 PG 9 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA FM895 UT WOS:A1991FM89500002 PM 1651105 ER PT J AU MARGOLIN, KA ARONSON, FR SZNOL, M ATKINS, MB CIOBANU, N FISHER, RI WEISS, GR DOROSHOW, JH BAR, MH HAWKINS, MJ MIER, JW PAIETTA, E GAYNOR, EP BOLDT, DH AF MARGOLIN, KA ARONSON, FR SZNOL, M ATKINS, MB CIOBANU, N FISHER, RI WEISS, GR DOROSHOW, JH BAR, MH HAWKINS, MJ MIER, JW PAIETTA, E GAYNOR, EP BOLDT, DH TI PHASE-II TRIAL OF HIGH-DOSE INTERLEUKIN-2 AND LYMPHOKINE-ACTIVATED KILLER-CELLS IN HODGKINS-DISEASE AND NON-HODGKINS-LYMPHOMA SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE INTERLEUKIN-2; LYMPHOKINE-ACTIVATED KILLER CELLS; HODGKINS DISEASE; NON-HODGKINS LYMPHOMA ID INFUSION RECOMBINANT INTERLEUKIN-2; ADOPTIVE IMMUNOTHERAPY; LEUKOCYTE INTERFERON; MALIGNANT-LYMPHOMA; ALPHA-INTERFERON; PERIPHERAL-BLOOD; ADVANCED CANCER; ACUTE-LEUKEMIA; SOLID TUMORS; LYMPHOCYTES AB Interleukin-2 (IL-2) plus lymphokine-activated killer (LAK) cell therapy has antineoplastic activity in renal cancer and malignant melanoma. In order to explore the activity of this therapy in Hodgkin's disease and non-Hodgkin's lymphoma, the Extramural IL-2/LAK Working Group (ILWG) treated 27 patients on two protocols using high-dose IL-2 and autologous LAK cells. Two of 12 patients with Hodgkin's disease experienced partial responses lasting 6 and 12 weeks. No patient with non-Hodgkin's lymphoma responded (p = NS). The toxicities of therapy were similar to those reported by the ILWG from trials of IL-2/LAK in solid tumors, consisting of transient hemodynamic, cardiopulmonary, renal and hepatic dysfunction, skin rash, fever, and flu-like symptoms. In view of the low response rate and the brief duration of these responses, we do not recommend the regimens reported here for further investigation in Hodgkin's disease or non-Hodgkin's lymphomas. C1 CITY HOPE CANC RES CTR,EXTRAMURAL LYMPHOKINE ACTIVATED KILLER WORKING GRP IL2,DUARTE,CA. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. NEW ENGLAND MED CTR HOSP,BOSTON,MA 02111. ALBERT EINSTEIN CANC CTR,NEW YORK,NY. LOYOLA UNIV,MED CTR,MAYWOOD,IL 60153. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. NCI,DIV CANC THERAPY,INVEST DRUG BRANCH,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CM73702, N01-CM73703, N01-CM73704] NR 29 TC 21 Z9 21 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 JUN PY 1991 VL 10 IS 3 BP 214 EP 220 DI 10.1097/00002371-199106000-00008 PG 7 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA FM895 UT WOS:A1991FM89500008 PM 1868045 ER PT J AU JACOBSON, MA VANDERHORST, C CAUSEY, DM DEHLINGER, M HAFNER, R MILLS, J AF JACOBSON, MA VANDERHORST, C CAUSEY, DM DEHLINGER, M HAFNER, R MILLS, J TI INVIVO ADDITIVE ANTIRETROVIRAL EFFECT OF COMBINED ZIDOVUDINE AND FOSCARNET THERAPY FOR HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION (ACTG PROTOCOL 053) SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID AIDS-RELATED COMPLEX; PLACEBO-CONTROLLED TRIAL; AZIDOTHYMIDINE AZT; ANTIGEN LEVELS; DOUBLE-BLIND; P24 ANTIGEN; PHASE-I; SERUM; HIV; 3'-AZIDO-3'-DEOXYTHYMIDINE AB Zidovudine and foscarnet each have antiretroviral activity against human immunodeficiency virus (HIV) and, when combined in vitro, inhibit HIV replication in an additive or synergistic fashion. To determine if an in vivo additive or synergistic antiretroviral effect might result from combined therapy, six symptomatic HIV-infected patients were studied who had persistently quantifiable serum HIV p24 antigen despite 9-27 weeks of full-dose oral zidovudine therapy (1200 mg/day). These patients were given intravenous foscarnet (30 mg/kg every 8 h) for 2 weeks with continued oral zidovudine for 14 days, followed by zidovudine alone for 6 months. Serum p24 antigen concentrations decreased in all six patients during the period of combined therapy by a mean 53% (P = .005). Subsequently, serum p24 antigen levels rose to the baseline value in four patients after 4-14 weeks. As predicted from in vitro studies, combined treatment with zidovudine and foscarnet resulted in an additive in vivo effect, but the effect was transient. C1 UNIV CALIF SAN FRANCISCO, DEPT MED, SAN FRANCISCO, CA 94143 USA. UNIV N CAROLINA, DEPT MED, CHAPEL HILL, NC 27514 USA. UNIV SO CALIF, LOS ANGELES CTY HOSP, DEPT MED, LOS ANGELES, CA 90033 USA. NIAID, DIV AIDS, BETHESDA, MD 20892 USA. RP JACOBSON, MA (reprint author), SAN FRANCISCO GEN HOSP, MED SERV, WARD 84, BLDG 80, 995 POTRERO, SAN FRANCISCO, CA 94110 USA. FU NCRR NIH HHS [RR-00083]; NIAID NIH HHS [AI-27663] NR 18 TC 52 Z9 52 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 1991 VL 163 IS 6 BP 1219 EP 1222 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA FP534 UT WOS:A1991FP53400007 PM 1828075 ER PT J AU CLEMENS, JD VANLOON, F SACK, DA CHAKRABORTY, J RAO, MR AHMED, F HARRIS, JR KHAN, MR YUNUS, M HUDA, S KAY, BA SVENNERHOLM, AM HOLMGREN, J AF CLEMENS, JD VANLOON, F SACK, DA CHAKRABORTY, J RAO, MR AHMED, F HARRIS, JR KHAN, MR YUNUS, M HUDA, S KAY, BA SVENNERHOLM, AM HOLMGREN, J TI FIELD TRIAL OF ORAL CHOLERA VACCINES IN BANGLADESH - SERUM VIBRIOCIDAL AND ANTITOXIC ANTIBODIES AS MARKERS OF THE RISK OF CHOLERA SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID RURAL BANGLADESH; ESCHERICHIA-COLI; BREAST-MILK; IMMUNIZATION; VACCINATION; PROTECTION; RESPONSES; IMMUNITY; MUCOSAL; DISEASE AB The relationship of serum vibriocidal (VC) and IgG anti-cholera toxin (CT) antibodies to the risk of cholera was evaluated during the first year of follow-up of recipients of three oral doses of B subunit (BS)-whole-cell vaccine, whole-cell vaccine, or Escherichia coli K12 strain placebo in Bangladesh. Acute sera from 121 cholera patients were compared with sera from 2592 contemporaneous community controls. Each doubling of VC titer was associated, on average, with a 22%-47% reduction of cholera risk in the three groups. In contrast, in the two groups that did not receive BS, anti-CT titers were directly associated with cholera and thus served as markers of higher cholera risk. Each vaccine conferred approximately 65% protective efficacy against cholera, but antibody titers did not correlate with vaccine efficacy, indicating that serum VC and anti-CT antibodies are poor markers of the longitudinal pattern of vaccine efficacy. C1 INT CTR DIARRHOEL DIS RES,DHAKA,BANGLADESH. UNIV MARYLAND,SCH MED,CTR VACCINE DEV,BALTIMORE,MD 21201. JOHNS HOPKINS UNIV,SCH PUBL HLTH,DIV GEOG MED,BALTIMORE,MD 21218. CTR DIS CONTROL,DIV ENTER INFECT,ATLANTA,GA 30333. GOTHENBURG UNIV,SCH MED,DEPT MED MICROBIOL,S-41124 GOTHENBURG,SWEDEN. RP CLEMENS, JD (reprint author), NICHHD,DIV PREVENT RES,PREVENT RES PROGRAM,ROOM 640,EXECUT PL N,BETHESDA,MD 20892, USA. OI Harris, Jeffrey/0000-0001-8728-7195 NR 23 TC 65 Z9 69 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 1991 VL 163 IS 6 BP 1235 EP 1242 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA FP534 UT WOS:A1991FP53400010 PM 2037789 ER PT J AU VANLOON, FPL CLEMENS, JD SACK, DA RAO, MR AHMED, F CHOWDHURY, S HARRIS, JR ALI, M CHAKRABORTY, J KHAN, MR NEOGY, PK SVENNERHOLM, AM HOLMGREN, J AF VANLOON, FPL CLEMENS, JD SACK, DA RAO, MR AHMED, F CHOWDHURY, S HARRIS, JR ALI, M CHAKRABORTY, J KHAN, MR NEOGY, PK SVENNERHOLM, AM HOLMGREN, J TI ABO BLOOD-GROUPS AND THE RISK OF DIARRHEA DUE TO ENTEROTOXIGENIC ESCHERICHIA-COLI SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID FIELD TRIAL; CHOLERA; VACCINE; BANGLADESH; SEVERITY AB To determine whether blood group O persons are at higher risk for enterotoxigenic Escherichia coli (ETEC) diarrhea, a case-control study was done for 17 months among rural Bangladeshis who were under systematic surveillance for diarrhea. Cases were children < 3 years old who presented between 1 January 1985 and 1 June 1986 for care of heat labile (LT) or heat stabile toxin-producing ETEC diarrhea. Controls were of similar ages and were randomly selected from three community-based serosurveys between July 1985 and May 1986. No association between blood group O and ETEC diarrhea was found for the 510 cases and 641 controls, nor was an association evident for cases of each toxin phenotype. Further refinement of the case definition to include only patients with LT-ETEC diarrhea, without enteric copathogens, also failed to reveal a substantial association with blood group O. These data suggest that a strong association with ABO groups, analogous to that for cholera, does not exist for ETEC diarrhea. C1 INT CTR DIARRHOEL DIS RES,DHAKA,BANGLADESH. GOTHENBURG UNIV,S-41124 GOTHENBURG,SWEDEN. UNIV MARYLAND,CTR VACCINE DEV,BALTIMORE,MD 21201. NICHHD,PREVENT RES PROGRAM,BETHESDA,MD. CTR DIS CONTROL,CTR INFECT DIS,DIV BACTERIAL DIS,ENTER DIS BRANCH,ATLANTA,GA 30333. RP VANLOON, FPL (reprint author), JOHNS HOPKINS UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,POB 278,615 N WOLFE ST,BALTIMORE,MD 21205, USA. RI Ali, Mohammad/E-2365-2017; OI Ali, Mohammad/0000-0003-1410-388X; Harris, Jeffrey/0000-0001-8728-7195 NR 14 TC 15 Z9 15 U1 0 U2 3 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 JUN PY 1991 VL 163 IS 6 BP 1243 EP 1246 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA FP534 UT WOS:A1991FP53400011 PM 2037790 ER PT J AU KLION, AD MASSOUGBODJI, A SADELER, BC OTTESEN, EA NUTMAN, TB AF KLION, AD MASSOUGBODJI, A SADELER, BC OTTESEN, EA NUTMAN, TB TI LOIASIS IN ENDEMIC AND NONENDEMIC POPULATIONS - IMMUNOLOGICALLY MEDIATED DIFFERENCES IN CLINICAL PRESENTATION SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN LYMPHATIC FILARIASIS; LOA-LOA; PARASITE ANTIGEN; HYPERRESPONSIVE SYNDROME; ANTIBODY-RESPONSES; IGE RESPONSES; BRUGIA-MALAYI; LYMPHOCYTE-T; INFECTIONS; MANIFESTATIONS AB To define the clinical spectrum of loiasis more precisely and to begin to assess the immunologic basis for the difference in clinical manifestations between visitors to endemic areas and natives of these areas, 51 West African patients with loiasis were evaluated and compared with 42 infected expatriates. Microfilaremia was present in 90% and Calabar swellings in only 16% of the endemic patients. Conversely, only 10% of the expatriates were microfilaremic while 95% complained of Calabar swellings. The endemic population showed significantly decreased levels of peripheral blood eosinophils, parasite-specific IgG, and lymphocyte proliferation to parasite antigens compared with the nonendemic population. These findings support the hypothesis that differences in the modulation of the immune response to parasite antigen are responsible for the observed differences in clinical presentation between expatriate and endemic populations with loiasis. C1 CTR NATL HOSP COTONOU,SERV PARASITOL,COTONOU,BENIN. UNIV COTONOU,COTONOU,BENIN. RP KLION, AD (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. OI Klion, Amy/0000-0002-4986-5326 NR 51 TC 91 Z9 91 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 1991 VL 163 IS 6 BP 1318 EP 1325 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA FP534 UT WOS:A1991FP53400022 PM 2037798 ER PT J AU JACOBSON, MA DREW, WL FEINBERG, J ODONNELL, JJ WHITMORE, PV MINER, RD PARENTI, D AF JACOBSON, MA DREW, WL FEINBERG, J ODONNELL, JJ WHITMORE, PV MINER, RD PARENTI, D TI FOSCARNET THERAPY FOR GANCICLOVIR-RESISTANT CYTOMEGALOVIRUS RETINITIS IN PATIENTS WITH AIDS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID IMMUNOCOMPROMISED PATIENTS; VIRUS; ACYCLOVIR; INVITRO; 9-<2-HYDROXY-1-(HYDROXYMETHYL)ETHOXYMETHYL>GUANINE; 9-(1,3-DIHYDROXY-2-PROPOXYMETHYL)GUANINE; DISEASE AB Infections caused by cytomegalovirus (CMV) resistant in vitro to ganciclovir, defined as requiring > 6-mu-mol of ganciclovir for ED50 have developed in some AIDS patients with progressive CMV retinitis despite chronic ganciclovir therapy. Two such patients (CMV isolates ED50, 9.5-14.5-mu-mol) were treated with foscarnet, an antiviral pyrophosphate analogue to which both patients' isolates demonstrated in vitro susceptibility (ED50, less-than-or-equal-to 300-mu-mol). Each patient had documented retinitis progression, at 2- and 1- to 5-week intervals, respectively, despite high-dose intravenous ganciclovir therapy. Both patients responded to foscarnet therapy with cessation of viral shedding in urine and blood. After foscarnet therapy was started, retinitis stabilized in the two patients for 12 and 25 weeks, respectively, before progression recurred. Therefore, foscarnet may be effective in immunocompromised patients with rapidly progressive CMV retinitis whose CMV isolates have developed in vitro resistance to ganciclovir. C1 UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT LAB MED,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT OPHTHALMOL,SAN FRANCISCO,CA 94143. SAN FRANCISCO GEN HOSP,OPHTHALMOL SERV,SAN FRANCISCO,CA 94110. MT ZION HOSP & MED CTR,DEPT LAB MED,SAN FRANCISCO,CA 94120. NIAID,DIV AIDS,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,MED CTR,DEPT OPHTHALMOL,WASHINGTON,DC 20037. GEORGE WASHINGTON UNIV,MED CTR,DEPT MED,WASHINGTON,DC 20037. RP JACOBSON, MA (reprint author), SAN FRANCISCO GEN HOSP,MED SERV,WARD 84,BLDG 80,995 POTRERO,SAN FRANCISCO,CA 94110, USA. FU NIAID NIH HHS [AI-27663] NR 15 TC 109 Z9 111 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 JUN PY 1991 VL 163 IS 6 BP 1348 EP 1351 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA FP534 UT WOS:A1991FP53400027 PM 1645385 ER PT J AU FLANIGAN, TP SCHWAN, TG ARMSTRONG, C VANVORIS, LP SALATA, RA AF FLANIGAN, TP SCHWAN, TG ARMSTRONG, C VANVORIS, LP SALATA, RA TI RELAPSING FEVER IN THE UNITED-STATES VIRGIN-ISLANDS - A PREVIOUSLY UNRECOGNIZED FOCUS OF INFECTION SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter C1 CASE WESTERN RESERVE UNIV HOSP,DEPT MED,CLEVELAND,OH 44106. NIAID,ROCKY MT LAB,HAMILTON,MT 59840. HAMOT MED CTR,ERIE,PA. NR 7 TC 7 Z9 7 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 1991 VL 163 IS 6 BP 1391 EP 1392 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA FP534 UT WOS:A1991FP53400043 PM 2037807 ER PT J AU LARSEN, CG KRISTENSEN, M PALUDAN, K DELEURAN, B THOMSEN, MK ZACHARIAE, COC KRAGBALLE, K MATSUSHIMA, K THESTRUPPEDERSEN, K AF LARSEN, CG KRISTENSEN, M PALUDAN, K DELEURAN, B THOMSEN, MK ZACHARIAE, COC KRAGBALLE, K MATSUSHIMA, K THESTRUPPEDERSEN, K TI THE ENDOGENOUS MEDIATOR 1,25(OH)2-D3 IS A POTENT REGULATOR OF INTERLEUKIN-1 INDUCED INTERLEUKIN-8 EXPRESSION AND PRODUCTION SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 MARSELISBORG UNIV HOSP,DEPT DERMATOL,AARHUS,DENMARK. LEO PHARMACEUT PROD,BALLERUP,DENMARK. NCI,LMI,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUN PY 1991 VL 96 IS 6 BP 1008 EP 1008 PG 1 WC Dermatology SC Dermatology GA FR857 UT WOS:A1991FR85700095 ER PT J AU ZACHARIAE, COC THESTRUPPEDERSEN, K MATSUSHIMA, K AF ZACHARIAE, COC THESTRUPPEDERSEN, K MATSUSHIMA, K TI EXPRESSION AND SECRETION OF LEUKOCYTE CHEMOTACTIC CYTOKINES BY NORMAL HUMAN MELANOCYTES AND MELANOMA-CELLS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 MARSELIBORG HOSP,DEPT DERMATOL,DK-8000 AARHUS C,DENMARK. NCI,BRMP,LMI,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUN PY 1991 VL 96 IS 6 BP 1011 EP 1011 PG 1 WC Dermatology SC Dermatology GA FR857 UT WOS:A1991FR85700113 ER PT J AU HAUSER, C SAURAT, JH WALDVOGEL, FA IZUI, S MORSE, HC ADORINI, L CERNY, A AF HAUSER, C SAURAT, JH WALDVOGEL, FA IZUI, S MORSE, HC ADORINI, L CERNY, A TI LANGERHANS CELL (LC) FUNCTION IN MURINE AIDS (MAIDS) SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 HOP CANTONAL GENEVA,DEPT DERMATOL,CH-1211 GENEVA 4,SWITZERLAND. HOP CANTONAL GENEVA,DEPT MED,CH-1211 GENEVA 4,SWITZERLAND. HOP CANTONAL GENEVA,DEPT PATHOL,CH-1211 GENEVA 4,SWITZERLAND. SANDOZ LTD,CH-4002 BASEL,SWITZERLAND. NIH,IMMUNOPATHOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUN PY 1991 VL 96 IS 6 BP 1014 EP 1014 PG 1 WC Dermatology SC Dermatology GA FR857 UT WOS:A1991FR85700135 ER PT J AU RAPPERSBERGER, K ROOS, N STANLEY, JR AF RAPPERSBERGER, K ROOS, N STANLEY, JR TI PEMPHIGUS FOLIACEUS (PF) AUTOANTIBODIES BIND TO AN EXTRACELLULAR DESMOSOMAL DOMAIN SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. UNIV OSLO,DEPT BIOL,ELECTRONMICROSCOP LABS,OSLO 3,NORWAY. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUN PY 1991 VL 96 IS 6 BP 1031 EP 1031 PG 1 WC Dermatology SC Dermatology GA FR857 UT WOS:A1991FR85700231 ER PT J AU SZEBENI, J WEINSTEIN, JN AF SZEBENI, J WEINSTEIN, JN TI DIPYRIDAMOLE BINDING TO PROTEINS IN HUMAN PLASMA AND TISSUE-CULTURE MEDIA SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID COLON CANCER-CELLS; CYTO-TOXICITY; METHOTREXATE TOXICITY; ORAL DIPYRIDAMOLE; POTENTIATION; TRIAL; ACIVICIN; INVITRO; PHARMACOKINETICS; 5-FLUOROURACIL AB Dipyridamole (Persantin), a commonly used coronary vasodilator and antithrombotic drug, has been intensively studied for its potential use in combination chemotherapy for cancer, and, recently, for acquired immunodeficiency syndrome. However, the strong binding of dipyridamole to proteins in human plasma complicates quantitative extrapolations from in vitro data to the clinic. To aid in such extrapolations, we incubated dipyridamole in human plasma and in tissue culture media containing 10% fetal calf serum (FCS), and determined the equilibrium levels of free drug. In human plasma, after addition of 2 to 10-mu-mol/L dipyridomole (i.e., in the therapeutically relevant concentration range), the fraction of free drug averaged between 1.9% and 3.5%. In 10% FCS, after addition of 0.08 to 5-mu-mol/L dipyridamole (i.e., the experimentally relevant concentration range), mean free fractions were in the 75% to 100% range. Relating various total dipyridamole levels in the therapeutically relevant range in human plasma to those in 10% FCS that provided identical fractions of free drug gave ratios in the 24 to 55 range. Thus, a multiplication factor in the above range is suggested for the interconversion of in vitro and in vivo dipyridamole concentrations that provide equivalent levels of free drug. RP SZEBENI, J (reprint author), NCI,MATH BIOL LAB,THEORET IMMUNOL SECT,BLDG 10,ROOM 4B-56,BETHESDA,MD 20892, USA. NR 38 TC 9 Z9 10 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD JUN PY 1991 VL 117 IS 6 BP 485 EP 492 PG 8 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA FQ781 UT WOS:A1991FQ78100009 PM 2045716 ER PT J AU KHAN, AS GALVIN, TA JENNINGS, MB GARDNER, MB LOWENSTINE, LJ AF KHAN, AS GALVIN, TA JENNINGS, MB GARDNER, MB LOWENSTINE, LJ TI SIV OF STUMP-TAILED MACAQUE (SIVSTM) IS A DIVERGENT ASIAN ISOLATE SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article; Proceedings Paper CT MEETING ON NONHUMAN PRIMATE MODELS FOR AIDS CY 1990 CL DELTA PRIMATE RES CTR, COVINGTON, LA HO DELTA PRIMATE RES CTR DE LENTIVIRUS; AIDS; LONG TERMINAL REPEAT; MACAQUE ID SIMIAN IMMUNODEFICIENCY VIRUS; T-LYMPHOTROPIC RETROVIRUS; AFRICAN-GREEN MONKEYS; HTLV-III; SEROEPIDEMIOLOGIC SURVEY; CERCOCEBUS-ATYS; CELL-LINES; LENTIVIRUS; ANTIBODIES; AIDS AB Analysis of molecularly cloned DNAs of SIVs isolated from Asian rhesus macaque (Macaca mulatta; SIV(mac)) and pig-tailed macaque (Macaca nemestrina; SIV(mne)) has indicated a high degree of sequence homology between these viruses. Thus SIV(mac) and SIV(mne) might have originated from the same or very closely related viruses. We have cloned and sequenced a PCR-amplified segment containing the LTR sequences of SIV originating from a stump-tailed macaque (Macaca arctoides; SIV(stm)). Comparative sequence analysis indicates that SIV(stm) belongs to the SIV/HIV-2 group, however, it is genetically distinct from the other members. C1 UNIV CALIF DAVIS,SCH MED,DEPT MED PATHOL,DAVIS,CA 95616. UNIV CALIF DAVIS,SCH VET MED,DEPT PATHOL,DAVIS,CA 95616. UNIV CALIF DAVIS,CALIF PRIMATE RES CTR,DAVIS,CA 95616. RP KHAN, AS (reprint author), NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892, USA. NR 24 TC 6 Z9 6 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD JUN PY 1991 VL 20 IS 4 BP 167 EP 171 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA GK919 UT WOS:A1991GK91900006 PM 1719204 ER PT J AU NOVEMBRE, FJ HIRSCH, VM MCCLURE, HM JOHNSON, PR AF NOVEMBRE, FJ HIRSCH, VM MCCLURE, HM JOHNSON, PR TI MOLECULAR DIVERSITY OF SIVSMM PBJ AND A COGNATE VARIANT, SIVSMM PGG SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article; Proceedings Paper CT MEETING ON NONHUMAN PRIMATE MODELS FOR AIDS CY 1990 CL DELTA PRIMATE RES CTR, COVINGTON, LA HO DELTA PRIMATE RES CTR ID SIMIAN IMMUNODEFICIENCY VIRUSES; SIV/SMM AB The molecular diversity of SIV(smm)/PBj proviral genomes in tissues of an infected macaque was analyzed. Molecular clones derived directly from intestinal tissue DNA were heterogenous, and contained LTRs with one or two NF-kB binding sites. LTRs with one NF-kB site predominated (approximately 75%). Virions derived from biologically active chimeric DNA clones with one or two NF-kB sites did not induce the acute death syndrome characteristic of PBj infection. These results suggest that either the duplicated NF-kB site acts in concert with other important viral determinants, or plays no role in producing the PBj syndrome. C1 NIAID,INFECT DIS LAB,TWINBROOK 2,12441 PARKLAWN DR,ROCKVILLE,MD 20852. GEORGETOWN UNIV,DEPT MICROBIOL,ROCKVILLE,MD. YERKES REG PRIMATE RES CTR,DIV PATHOBIOL & IMMUNOL,ATLANTA,GA. EMORY UNIV,DEPT PATHOL,ATLANTA,GA 30322. RI Johnson, Philip/A-6892-2009 FU NCRR NIH HHS [RR-00165]; NIAID NIH HHS [N01-AI-72623] NR 11 TC 17 Z9 17 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD JUN PY 1991 VL 20 IS 4 BP 188 EP 192 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA GK919 UT WOS:A1991GK91900010 PM 1942009 ER PT J AU OCHS, HD MORTON, WR TSAI, CC THOULESS, ME ZHU, Q KULLER, LD WU, YP BENVENISTE, RE AF OCHS, HD MORTON, WR TSAI, CC THOULESS, ME ZHU, Q KULLER, LD WU, YP BENVENISTE, RE TI MATERNAL FETAL TRANSMISSION OF SIV IN MACAQUES - DISSEMINATED ADENOVIRUS INFECTION IN AN OFFSPRING WITH CONGENITAL SIV INFECTION SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article; Proceedings Paper CT MEETING ON NONHUMAN PRIMATE MODELS FOR AIDS CY 1990 CL DELTA PRIMATE RES CTR, COVINGTON, LA HO DELTA PRIMATE RES CTR DE CONGENITAL SIV INFECTION; SAIDS IN INFANT MACAQUES; IMMUNOHISTOCHEMICAL ASSESSMENT; ADENOVIRUS IN IMMUNE-COMPROMISED HOSTS ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE-DEFICIENCY; HEPATIC-NECROSIS; LENTIVIRUS; ANTIBODIES; CHILDREN; MOTHERS; BORN AB To develop a nonhuman primate model for maternal-fetal transmission of HIV infection, we have inoculated pregnant Macaca nemestrina with uncloned SIV(Mne). Three animals inoculated during the third trimester delivered healthy infants. One of the three infants, a male born 31 days after the mother was inoculated with SIV, became virus-positive but failed to produce SIV-specific antibody and died with overt simian immunodeficiency and disseminated adenovirus (SV20) infection at age six and one-half months. SIV and adenovirus antigen could be demonstrated by immunohistochemical methods in multiple organ systems. C1 NCI,FREDERICK,MD 21701. UNIV WASHINGTON,REG PRIMATE RES CTR,SEATTLE,WA 98195. RP OCHS, HD (reprint author), UNIV WASHINGTON,SCH MED,DEPT PEDIAT,RD-20,SEATTLE,WA 98195, USA. NR 18 TC 32 Z9 32 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD JUN PY 1991 VL 20 IS 4 BP 193 EP 200 PG 8 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA GK919 UT WOS:A1991GK91900011 PM 1658326 ER PT J AU WHITE, L GARCIA, D BOHER, Y BLANCO, M PEREZ, M ROMER, H FLORES, J PEREZSCHAEL, I AF WHITE, L GARCIA, D BOHER, Y BLANCO, M PEREZ, M ROMER, H FLORES, J PEREZSCHAEL, I TI TEMPORAL DISTRIBUTION OF HUMAN ROTAVIRUS SEROTYPE-1, SEROTYPE-2, SEROTYPE-3, AND SEROTYPE-4 IN VENEZUELAN CHILDREN WITH GASTROENTERITIS DURING 1979-1989 SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE ROTAVIRUS; DIARRHEA; DISEASE ID LINKED IMMUNOSORBENT-ASSAY; MONOCLONAL-ANTIBODIES; ENZYME-IMMUNOASSAY; INFANTS; CONSERVATION; INFECTION; DIARRHEA AB The temporal distribution and clinical severity of rotavirus VP7 serotypes 1, 2, 3, and 4 recovered from 427 Venezuelan children with acute gastroenteritis over a period of 11 years were studied. Rotavirus VP7 serotype was established by ELISA serotyping in 298 (69.78%) of the specimens while the serotype of the remaining 129 (30.21%) samples could not be determined. Of the specimens typed, 85 (19.90% of the total) were serotype 1, 43 (10.07%) were serotype 2, 105 (24.59%) were serotype 3, and 65 (15.22%) were serotype 4. Yearly changes in the frequency of individual serotypes were observed. The predominance of a single serotype with minor contribution from others was noted every year. In this study, serotype 1 appears to induce a less severe illness in comparison with serotypes 2,3, and 4. No apparent association between the proportion of each serotype and the children's age were found. C1 UNIV CENT VENEZUELA,MINIST SANIDAD & ASISTENCIA SOCIAL,INST BIOMED,AP 4043,CARACAS 1010A,VENEZUELA. HOSP NINOS JM DE LOS RIOS,CARACAS,VENEZUELA. NIH,INFECT DIS LAB,BETHESDA,MD 20892. NR 23 TC 24 Z9 27 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 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD JUN PY 1991 VL 34 IS 2 BP 79 EP 84 DI 10.1002/jmv.1890340202 PG 6 WC Virology SC Virology GA FU971 UT WOS:A1991FU97100001 PM 1653820 ER PT J AU DALE, JK DIBISCEGLIE, AM HOOFNAGLE, JH STRAUS, SE AF DALE, JK DIBISCEGLIE, AM HOOFNAGLE, JH STRAUS, SE TI CHRONIC FATIGUE SYNDROME - LACK OF ASSOCIATION WITH HEPATITIS-C VIRUS-INFECTION SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE HCV; CHRONIC FATIGUE SYNDROME; SEROPREVALENCE STUDY; CHRONIC NON-A-HEPATITIS, NON-B-HEPATITIS ID NON-B-HEPATITIS; NON-A-HEPATITIS; CONTROLLED TRIAL; ACYCLOVIR AB Chronic fatigue syndrome (CFS) is a debilitating heterogeneous disorder lacking consistent, objective physical or laboratory abnormalities. Among the hypothetical etiologies for CFS are chronic viral infections. The present controlled seroprevalence study found that, among typical CFS patients, evidence of hepatitis C virus (HCV) infection is uncommon. Only one of 36 patients and none of 14 controls were anti-HCV positive. The positive patient had persistent aminotransferase elevations and prior posttransfusion hepatitis. Thus HCV infection is not a common feature of CFS and should not be routinely sought. C1 NIAID,CLIN INVEST LAB,MED VIROL SECT,BLDG 10,ROOM 11N113,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NIDDKD,LIVER DIS SECT,BETHESDA,MD. NR 17 TC 21 Z9 21 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 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD JUN PY 1991 VL 34 IS 2 BP 119 EP 121 DI 10.1002/jmv.1890340209 PG 3 WC Virology SC Virology GA FU971 UT WOS:A1991FU97100008 PM 1653818 ER PT J AU LOPEZ, S SIMONS, SS AF LOPEZ, S SIMONS, SS TI DEXAMETHASONE 21-(BETA-ISOTHIOCYANATOETHYL) THIOETHER - A NEW AFFINITY LABEL FOR GLUCOCORTICOID RECEPTORS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID STEROID-BINDING DOMAIN; ESTROGEN-RECEPTOR; FUNCTIONAL-GROUP; AMINO-ACID; 21-MESYLATE; COVALENT; IDENTIFICATION; AZIRIDINE; BIOACTIVITY; COMPLEXES AB The C-21 methanesulfonate ester of the synthetic glucocorticoid dexamethasone (Dex) is an efficient electrophilic affinity label of glucocorticoid receptors and exhibits irreversible antiglucocorticoid activity. In an effort to obtain other affinity labeling steroids with differing biological activities, several new derivatives of Dex were prepared which contained a reactive electrophilic substituent at various distances from the C-21 position. All compounds displayed relatively low affinity for rat glucocorticoid receptors (less-than-or-equal-to 8% of that of Dex) in a cell-free competition assay. Nevertheless, one compound, dexamethasone 21-(beta-isothiocyanatoethyl) thioether (Dex-NCS), appeared to be an affinity label by virtue of its ability to block the cell-free exchange binding of [H-3]Dex. [H-3]Dex-NCS was thus synthesized and reacted with cell-free receptors to give, after analysis on denaturing SDS-polyacrylamide gels, only one specifically labeled species at 98 kDa, which is the molecular weight of authentic rat glucocorticoid receptor. These data directly establish Dex-NCS as a new affinity label for glucocorticoid receptors. Data on the reactivity of Dex-NCS and the stability of [H-3]Dex-NCS-labeled receptors suggest that a cysteine SH group has been labeled. C1 NIDDK,LMCB,STEROID HORMONES SECT,BLDG 8,ROOM B2A-07,BETHESDA,MD 20892. NR 38 TC 9 Z9 9 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN PY 1991 VL 34 IS 6 BP 1762 EP 1767 DI 10.1021/jm00110a002 PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA FR690 UT WOS:A1991FR69000002 PM 2061919 ER PT J AU SPIVAK, CE WATERS, JA YADAV, JS SHANG, WC HERMSMEIER, M LIANG, RF GUND, TM AF SPIVAK, CE WATERS, JA YADAV, JS SHANG, WC HERMSMEIER, M LIANG, RF GUND, TM TI (-/+)-OCTAHYDRO-2-METHYL-TRANS-5 (1H)-ISOQUINOLONE METHIODIDE - A PROBE THAT REVEALS A PARTIAL MAP OF THE NICOTINIC RECEPTORS RECOGNITION SITE SO JOURNAL OF MOLECULAR GRAPHICS LA English DT Article DE NICOTINIC RECEPTOR; RECEPTOR MAP; NICOTINIC AGONIST; MOLECULAR MODELING ID AGONISTS; ACETYLCHOLINE; PHARMACOLOGY; ANALOGS AB A new, semirigid, nicotinic agonist (+/-)-octahydro-2-methyl-trans-5 (H-1)-isoquinolone methiodide was synthesized. The disposition of this agonist's nitrogen and carbonyl group conforms well to the prevailing notion of a pharmacophore for the nicotinic receptor. Comparing its structure and electrostatic potential surfaces, we predicted that its activity would be similar to that of carbamylcholine at the frog neuromuscular junction. Instead, the potency of the isoquinolone was only 0.015 times as potent as (+)-carbamylcholine. We conclude, after eliminating other possibilities, that the vicinity of the carbonyl group of an agonist must be planar to fit a confined space within the receptor's recognition site. The isoquinolone is a weak agonist because its methylene group beta-to the carbonyl intrudes on this space. C1 NIDDKD,BIO-ORGAN CHEM,BETHESDA,MD. NEW JERSEY INST TECHNOL,DEPT CHEM & CHEM ENGN,NEWARK,NJ 07102. RP SPIVAK, CE (reprint author), NIDA,ADDICT RES CTR,BALTIMORE,MD, USA. NR 30 TC 1 Z9 1 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0263-7855 J9 J MOL GRAPHICS JI J. Mol. Graph. PD JUN PY 1991 VL 9 IS 2 BP 105 EP & DI 10.1016/0263-7855(91)85006-K PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Computer Science, Interdisciplinary Applications; Crystallography; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Crystallography; Mathematical & Computational Biology GA FR838 UT WOS:A1991FR83800005 PM 1768639 ER PT J AU FUKUI, S SCHWARCZ, R RAPOPORT, SI TAKADA, Y SMITH, QR AF FUKUI, S SCHWARCZ, R RAPOPORT, SI TAKADA, Y SMITH, QR TI BLOOD-BRAIN-BARRIER TRANSPORT OF KYNURENINES - IMPLICATIONS FOR BRAIN SYNTHESIS AND METABOLISM SO JOURNAL OF NEUROCHEMISTRY LA English DT Article ID EXCITOTOXIN QUINOLINIC ACID; RAT-BRAIN; CEREBROSPINAL-FLUID; AMINO-ACIDS; 3-HYDROXYANTHRANILIC ACID; CEREBROVASCULAR TRANSPORT; PERFUSION TECHNIQUE; CONTENT INCREASES; MAMMALIAN BRAIN; L-TRYPTOPHAN AB To evaluate the potential contribution of circulating kynurenines to brain kynurenine pools, the rates of cerebral uptake and mechanisms of blood-brain barrier transport were determined for several kynurenine metabolites of tryptophan, including L-kynurenine (L-KYN), 3-hydroxykynurenine (3-HKYN), 3-hydroxyanthranilic acid (3-HANA), anthranilic acid (ANA), kynurenic acid (KYNA), and quinolinic acid (QUIN), in pentobarbital-anesthetized rats using an in situ brain perfusion technique. L-KYN was found to be taken up into brain at a significant rate [permeability-surface area product (PA) = 2-3 x 10(-3) ml/s/g] by the large neutral amino acid carrier (L-system) of the blood-brain barrier. Best-fit estimates of the V(max) and K(m) of saturable L-KYN transfer equalled 4.5 x 10(-4)-mu-mol/s/g and 0.16-mu-mol/ml, respectively. The same carrier may also mediate the brain uptake of 3-HKYN as D,L-3-HKYN competitively inhibited the brain transfer of the large neutral amonio acid L-leucine. For the other metabolites, uptake appeared mediated by passive diffusion. This occurred at a significant rate for ANA (PA, 0.7-1.6 x 10(-3) ml/s/g), and at far lower rates (PA, 2-7 x 10(-5) ml/s/g) for 3-HANA, KYNA, and QUIN. Transfer for KYNA, 3-HANA, and ANA also appeared to be limited by plasma protein binding. The results demonstrate the saturable transfer of L-KYN across the blood-brain barrier and suggest that circulating L-KYN, 3-HKYN, and ANA may each contribute significantly to respective cerebral pools. In contrast, QUIN, KYNA, and 3-HANA cross the blood-brain barrier poorly, and therefore are not expected to contribute significantly to brain pools under normal conditions. C1 NIA,NEUROSCI LAB,BLDG 10,ROOM 6C-103,BETHESDA,MD 20892. MARYLAND PSYCHIAT RES CTR,BALTIMORE,MD 21228. NR 56 TC 323 Z9 327 U1 2 U2 16 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 1991 VL 56 IS 6 BP 2007 EP 2017 DI 10.1111/j.1471-4159.1991.tb03460.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA FT883 UT WOS:A1991FT88300024 PM 1827495 ER PT J AU GRILLI, M WRIGHT, AG HANBAUER, I AF GRILLI, M WRIGHT, AG HANBAUER, I TI CHARACTERIZATION OF [H-3] DOPAMINE UPTAKE SITES AND [H-3] COCAINE RECOGNITION SITES IN PRIMARY CULTURES OF MESENCEPHALIC NEURONS DURING INVITRO DEVELOPMENT SO JOURNAL OF NEUROCHEMISTRY LA English DT Article ID NOREPINEPHRINE UPTAKE SITES; RAT SUBSTANTIA-NIGRA; -LABELED DESIPRAMINE; DOPAMINERGIC-NEURONS; COCAINE BINDING; BRAIN; MEMBRANES; COMPLEX; CELLS; MPTP AB [H-3]Dopamine uptake and [H-3]cocaine binding sites were studied in primary cultures of ventral mesencephalon from 14-day-old rat embryos. Specific binding sites for [H-3]cocaine and [H-3]mazindol were detected only in intact cell cultures of ventral mesencephalon, and were absent in sonicated, washed membranes prepared from these cell cultures. [H-3]Cocaine was not taken up by the cells through an active transport process because [H-3]cocaine binding occurred also at 4-degrees-C. Moreover, the possibility of [H-3]cocaine entering the cells by passive diffusion and ion trapping was also excluded because extensive washing failed to remove [H-3]cocaine from the cells. [H-3]Cocaine binding was reduced to 6% of control when cells were permeabilized with streptolysin O (0.2 U/ml, 5 min). Taken together, these results suggest that in cultured mesencephalic neurons, [H-3]cocaine may enter the cell by passive diffusion and then be sequestered by a cytosolic compartment that is lost in the process of permeabilization or sonication and washing of membrane preparations. Permeabilization of cultured neurons failed to alter the storage of [H-3]dopamine. When cells were permeabilized with streptolysin O (0.2 U/ml; 5 min) after [H-3]dopamine was taken up, [H-3]dopamine was retained by the cells and did not leak into the incubation medium, indicating that [H-3]dopamine was stored in sites that could not pass through the perforated membranes. In contrast, [H-3]dopamine uptake into already permeabilized cells was reduced by 33%, suggesting that a cytosolic protein that had leaked out may play a functional role in the uptake process. In contrast to striatal membrane preparations of adult rats, [H-3]cocaine binding in intact mesencephalic cell cultures was Na+ independent. The expression of [H-3]dopamine uptake and [H-3]cocaine binding sites appeared to be developmentally linked to neuritic outgrowth, supporting the view that cocaine binding sites may be closely associated with the dopamine transporter. C1 NHLBI,CHEM PHARMACOL LAB,BLDG 10,RM 8N-102,BETHESDA,MD 20892. NR 24 TC 16 Z9 17 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 JUN PY 1991 VL 56 IS 6 BP 2108 EP 2115 DI 10.1111/j.1471-4159.1991.tb03473.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA FT883 UT WOS:A1991FT88300037 PM 2027018 ER PT J AU ROSE, JW LORBERBOUMGALSKI, H FITZGERALD, D MCCARRON, R HILL, KE TOWNSEND, JJ PASTAN, I AF ROSE, JW LORBERBOUMGALSKI, H FITZGERALD, D MCCARRON, R HILL, KE TOWNSEND, JJ PASTAN, I TI CHIMERIC CYTOTOXIN IL2-PE40 INHIBITS RELAPSING EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE CHIMERIC CYTOTOXIN; PSEUDOMONAS EXOTOXIN; INTERLEUKIN-2; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS ID MYELIN BASIC-PROTEIN; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; ANTI-IL-2 RECEPTOR ANTIBODY; CARDIAC ALLOGRAFT SURVIVAL; ADOPTIVE TRANSFER; INDUCED ARTHRITIS; LYMPHOCYTES-T; MICE; CELLS; INTERLEUKIN-2 AB IL2-PE40 is a chimeric protein composed of human interleukin-2 (IL2) genetically fused to a modified form of Pseudomonas exotoxin lacking the cell recognition domain. IL2-PE40 is cytotoxic for IL2 receptor-bearing lymphocytes in culture and can inhibit activation of T cells in vivo. IL2-PE40 can significantly diminish antigen-stimulated proliferation of lymphocytes sensitized to myelin basic protein. Intraperitoneal administration of IL2-PE40 not only markedly inhibits the clinical manifestations of adoptively transferred relapsing experimental allergic encephalomyelitis but also dramatically reduces both inflammation and demyelination characteristic of the disease. C1 UNIV UTAH,DEPT NEUROL,SALT LAKE CITY,UT 84112. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NINCDS,NEUROPATHOL & NEUROANAT SCI LAB,BETHESDA,MD 20892. UNIV UTAH,DEPT PATHOL,SALT LAKE CITY,UT 84112. VET ADM MED CTR,DEPT PATHOL,SALT LAKE CITY,UT 84148. RP ROSE, JW (reprint author), VET ADM MED CTR,NEUROVIROL RES LAB 151B,500 FOOTHILL DR,SALT LAKE CITY,UT 84148, USA. NR 22 TC 26 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JUN PY 1991 VL 32 IS 3 BP 209 EP 217 DI 10.1016/0165-5728(91)90190-I PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA FP394 UT WOS:A1991FP39400003 PM 1709644 ER PT J AU DUFFY, CJ WURTZ, RH AF DUFFY, CJ WURTZ, RH TI SENSITIVITY OF MST NEURONS TO OPTIC FLOW STIMULI .1. A CONTINUUM OF RESPONSE SELECTIVITY TO LARGE-FIELD STIMULI SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID CORTICAL AREAS MT; OCULAR FOLLOWING RESPONSES; SUPERIOR TEMPORAL SULCUS; PURSUIT EYE-MOVEMENTS; POSTERIOR PARIETAL CORTEX; MACAQUE MONKEY; FUNCTIONAL-PROPERTIES; VISUAL AREA; EXPANSION CONTRACTION; ROTATION CELLS AB 1. Neurons in the dorsomedial region of the medial superior temporal area (MSTd) have large receptive fields that include the fovea, are directionally selective for moving visual stimuli, prefer the motion of large fields to small spots, and respond to rotating and expanding patterns of motion as well as frontal parallel planar motion. These characteristics suggested that these neurons might contribute to the analysis of the large-field optic flow stimulation generated as an observer moves through the visual environment. 2. We tested the response of MSTd neurons in two awake monkeys by systematically presenting a set of translational and rotational stimuli to each neuron. These 100 x 100-degrees stimuli were the motion components from which all optic flow fields are derived. 3. In 220 single neurons we found 23% that responded primarily to one component of motion (planar, circular, or radial), 34% that responded to two components (planocircular or planoradial, but never circuloradial), and 29% that responded to all three components. 4. The number of stimulus components to which a neuron responded was unrelated to the size or eccentricity of its receptive field. 5. Triple-, double-, and single-component neurons varied widely in the strength of their responses to the preferred components. Grouping these neurons together revealed that they did not form discrete classes but rather a continuum of response selectivity. 6. This continuum was apparent in other response characteristics. Direction selectivity was weakest in triple-component neurons, strongest in single-component neurons. Significant inhibitory responses were less frequent in triple-component neurons than in single-component neurons. 7. There was some indication that the neurons of similar component classes occupied adjacent regions within MSTd, but all combinations of component and direction selectivity were occasionally found in immediate juxtaposition. 8. Experiments on a subset of neurons showed that the speed of motion, the dot density, and the number of different speed planes in the display had little influence on these responses. 9. We conclude that the selective responses of many MSTd neurons to the rotational and translational components of optic flow make these neurons reasonable candidates for contributing to the analysis of optic flow fields. RP DUFFY, CJ (reprint author), NEI,SENSORIMOTOR RES LAB,BLDG 10,ROOM 10C101,BETHESDA,MD 20892, USA. NR 55 TC 629 Z9 633 U1 3 U2 13 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUN PY 1991 VL 65 IS 6 BP 1329 EP 1345 PG 17 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA FQ590 UT WOS:A1991FQ59000007 PM 1875243 ER PT J AU DUFFY, CJ WURTZ, RH AF DUFFY, CJ WURTZ, RH TI SENSITIVITY OF MST NEURONS TO OPTIC FLOW STIMULI .2. MECHANISMS OF RESPONSE SELECTIVITY REVEALED BY SMALL-FIELD STIMULI SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article AB 1. In these experiments we examined the receptive field mechanisms that support the optic flow field selective responses of neurons in the dorsomedial region of the medial superior temporal area (MSTd). Our experiments tested the predictions of two hypotheses of optic flow field selectivity. The direction mosaic hypothesis states that these receptive fields contain a set of planar direction-selective subfields that match the local directions of motion within optic flow fields. The vector field hypothesis states that these receptive fields are uniquely sensitive to distributed properties of planar, circular, or radial optic flow fields. 2. Experiments using large-field stimuli revealed that some neurons showed changes in optic flow field selectivity depending on the position of the stimulus in the receptive field; these are position-dependent responses. However, other neurons maintained the same optic flow field selectivities in spite of changes in stimulus position; these are position-invariant responses. We have used the position dependence or invariance of optic flow field selectivity as a way of testing the direction mosaic and vector field hypotheses. Position dependence is more consistent with the direction mosaic hypothesis, whereas position invariance is more consistent with the vector field hypothesis. 3. To test for position effects, we examined the optic flow field selectivity of small subfields within the large receptive fields of 160 MSTd neurons. First, we centered small-field optic flow stimuli of various sizes over the same position in the receptive field. Most MSTd neurons showed decreasing response amplitude with decreasing stimulus size but maintained optic flow field selectivity. 4. We then placed small-field stimuli at various positions within the large receptive field of these MSTd neurons. Position-invariant response selectivity was most prominent in single-component neurons, suggesting that they were more consistent with the vector field hypothesis. Position-dependent response selectivity was most prominent in triple-component neurons, suggesting that they were more consistent with the direction mosaic hypothesis. However, the variations in planar direction preference throughout the receptive field of these triple-component neurons were not consistent with a direction mosaic explanation of the large-field circular or radial selectivity observed. 5. Small-field position studies also demonstrated the existence of zones within the receptive field in which either direction-selective inhibitory or direction-selective excitatory responses predominated. The degree of overlap between these zones increased from nonselective to triple- to double- and finally to single-component neurons. 6. We suggest that the overlap of gradients of excitation and inhibition within the receptive field of these neurons might help to explain their responses to complex stimuli. Our hypothesis relies on quantitative variations in the relative strength, overlap, directions, and positions of excitatory and inhibitory planar response gradients. Changes in these parameters might account for the continuum of response types rather than discrete categories that characterize the responses of MSTd neurons to optic flow field stimuli. RP DUFFY, CJ (reprint author), NEI,SENSORIMOTOR RES LAB,BLDG 10,RM 10C101,BETHESDA,MD 20892, USA. NR 7 TC 275 Z9 277 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUN PY 1991 VL 65 IS 6 BP 1346 EP 1359 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA FQ590 UT WOS:A1991FQ59000008 PM 1875244 ER PT J AU HYDE, TM HOTSON, JR KLEINMAN, JE AF HYDE, TM HOTSON, JR KLEINMAN, JE TI DIFFERENTIAL-DIAGNOSIS OF CHOREIFORM TARDIVE-DYSKINESIA SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Review ID CREUTZFELDT-JAKOB DISEASE; PAROXYSMAL KINESIGENIC CHOREOATHETOSIS; ADULT METACHROMATIC LEUKODYSTROPHY; NEURONAL CEROID-LIPOFUSCINOSIS; BASAL GANGLIA CALCIFICATIONS; DYSTONIC CHOREOATHETOSIS; HUNTINGTONS-DISEASE; PARKINSONS-DISEASE; CLINICAL FEATURES; MOVEMENT DISORDER AB Orofacial dyskinesias and choreiform movements of limbs occur with moderate frequency among psychiatric patients. Abnormal involuntary movements are symptoms of a wide variety of neurological and medical disorders. For both therapeutic and medicolegal reasons, psychiatric patients should be thoroughly evaluated before being given the diagnosis of tardive dyskinesia. This review presents the differential diagnosis of disorders associated with orofacial and appendicular choreiform involuntary movements. In addition, this paper provides a guide to the clinical and laboratory evaluation of patients with these symptoms. C1 NIMH,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. SANTA CLARA VALLEY MED CTR,DEPT NEUROL,SAN JOSE,CA 95128. STANFORD UNIV,MED CTR,DEPT NEUROL,STANFORD,CA 94305. NR 184 TC 10 Z9 11 U1 0 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SUM PY 1991 VL 3 IS 3 BP 255 EP 268 PG 14 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA GC876 UT WOS:A1991GC87600003 PM 1821242 ER PT J AU MITZ, AR GODSCHALK, M WISE, SP AF MITZ, AR GODSCHALK, M WISE, SP TI LEARNING-DEPENDENT NEURONAL-ACTIVITY IN THE PREMOTOR CORTEX - ACTIVITY DURING THE ACQUISITION OF CONDITIONAL MOTOR ASSOCIATIONS SO JOURNAL OF NEUROSCIENCE LA English DT Article ID INITIATED HAND MOVEMENTS; RHESUS-MONKEYS; MACAQUE MONKEYS; FUNCTIONAL-ORGANIZATION; PERIARCUATE NEURONS; AFFERENT PROPERTIES; VISUAL RESPONSES; FIELD POTENTIALS; INFERIOR AREA-6; CEREBRAL-CORTEX AB It has been proposed that the premotor cortex plays a role in the selection of motor programs based on environmental context. To test this hypothesis, we recorded the activity of single neurons as monkeys learned visuomotor associations. The hypothesis predicts that task-related premotor cortical activity before learning should differ from that afterward. We found that a substantial population of premotor cortex neurons, over half of those adequately tested, showed the predicted learning-dependent changes in activity. The present findings support a role for premotor cortex in motor preparation, generally, and suggest a specific role in the selection of movements on the basis of arbitrary associations. C1 NIMH,NEUROPHYSIOL LAB,POB 289,POOLESVILLE,MD 20837. NR 85 TC 237 Z9 239 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN PY 1991 VL 11 IS 6 BP 1855 EP 1872 PG 18 WC Neurosciences SC Neurosciences & Neurology GA FR284 UT WOS:A1991FR28400034 PM 2045890 ER PT J AU HIRSCHFELD, RMA SHEA, MT WEISE, R AF HIRSCHFELD, RMA SHEA, MT WEISE, R TI DEPENDENT PERSONALITY-DISORDER - PERSPECTIVES FOR DSM-IV SO JOURNAL OF PERSONALITY DISORDERS LA English DT Article ID AXIS-II; DIAGNOSTIC-CRITERIA; PANIC DISORDER; OUTPATIENT POPULATION; INTERNAL CONSISTENCY; SEX DISTRIBUTION; CO-MORBIDITY; DEPRESSION; PREVALENCE; MCMI C1 NIMH,MOOD ANXIETY & PERSONAL DISORDERS RES BRANCH,WASHINGTON,DC 20032. BROWN UNIV,DEPT PSYCHIAT & BEHAV SCI,PROVIDENCE,RI 02912. RP HIRSCHFELD, RMA (reprint author), UNIV TEXAS,MED BRANCH,DEPT PSYCHIAT & BEHAV SCI,GALVESTON,TX 77550, USA. NR 59 TC 19 Z9 19 U1 1 U2 2 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 SN 0885-579X J9 J PERS DISORD JI J. Pers. Disord. PD SUM PY 1991 VL 5 IS 2 BP 135 EP 149 PG 15 WC Psychiatry SC Psychiatry GA FU937 UT WOS:A1991FU93700005 ER PT J AU SCHEFFEL, U POGUN, S STATHIS, M BOJA, JW KUHAR, MJ AF SCHEFFEL, U POGUN, S STATHIS, M BOJA, JW KUHAR, MJ TI INVIVO LABELING OF COCAINE BINDING-SITES ON DOPAMINE TRANSPORTERS WITH [H-3] WIN-35,428 SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID RAT STRIATUM; H-3 COCAINE; SQUIRREL-MONKEYS; LIGAND-BINDING; BRAIN; BEHAVIOR; INHIBITION; RECEPTORS; ANALOGS; NOREPINEPHRINE AB After in vivo administration, [H-3]WIN 35,428 accumulated in mouse brain regions containing dopaminergic nerve terminals. The highest accumulation was in the striatum and it peaked between 30 and 60 min. The accumulation was saturable with increasing doses of WIN 35,428, and was blocked by compounds that bind to the dopamine transporter. Paroxetine, a drug that blocks serotonin transporters, had no effect. Moreover, the in vivo potency of cocaine analogs correlated with their in vitro potency. Thus, [H-3]WIN 35,428 is a suitable ligand for labeling cocaine receptors associated with dopamine transporters in vivo. C1 NIDA,ADDICT RES CTR,NEUROSCI BRANCH,POB 5180,BETHESDA,MD 21224. JOHNS HOPKINS MED INST,DEPT RADIOL,DIV NUCL MED,BALTIMORE,MD 21205. EGE UNIV,TIP FAK,FIZYOLOJ ANABILIM BALI,IZMIR 35100,TURKEY. RI Pogun, Sakire/A-5816-2010 FU NINDS NIH HHS [NS15080] NR 36 TC 58 Z9 58 U1 2 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUN PY 1991 VL 257 IS 3 BP 954 EP 958 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FQ593 UT WOS:A1991FQ59300005 PM 2046028 ER PT J AU GOZES, I MCCUNE, SK JACOBSON, L WARREN, D MOODY, TW FRIDKIN, M BRENNEMAN, DE AF GOZES, I MCCUNE, SK JACOBSON, L WARREN, D MOODY, TW FRIDKIN, M BRENNEMAN, DE TI AN ANTAGONIST TO VASOACTIVE-INTESTINAL-PEPTIDE AFFECTS CELLULAR FUNCTIONS IN THE CENTRAL-NERVOUS-SYSTEM SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CYCLASE-ACTIVATING POLYPEPTIDE; SPINAL-CORD CULTURES; ADENYLATE-CYCLASE; BINDING-SITES; STRUCTURAL REQUIREMENTS; NEUROTROPHIC ACTION; NEURONAL CULTURES; BRAIN MEMBRANES; CYCLIC-AMP; RAT-BRAIN AB A vasoactive intestinal peptide (VIP) antagonist was synthesized and used to investigate the interactions of VIP with its receptors present in the central nervous system (CNS). The VIP antagonist is a hybrid peptide consisting of a portion of VIP and a portion of neurotensin, designed to change the membrane permeability of the VIP portion. The hybrid antagonist displaced 80 to 90% of [I-125]VIP binding to cell cultures from cerebral cortex, hippocampus or spinal cord. The displacement curve was biphasic, suggesting two binding sites. In the case of cortical astrocytes, the antagonist had a K(i) of 45 pM at one site and a K(i) of 74 nM at the other. At the lower affinity binding site, the antagonist was about 10-fold more potent than VIP in displacing radiolabeled VIP. The accumulation of cyclic AMP (cAMP) in VIP-stimulated cortical glia cultures was decreased by the new antagonist (EC50, 59 nM). This decrease in cAMP was greater than that achieved in the presence of other putative VIP antagonists. Finally, the addition of 1 nM hybrid antagonist to dissociated spinal cord cultures resulted in a 42% reduction in neuronal cell counts as compared with controls, and the EC50 of this effect was about 30 pM, which corresponded closely to the K(i) of antagonist displacement of [I-125]VIP binding at the high-affinity site. The antagonist appears to be a competitive blocker for both VIP-mediated increases in cAMP formation or VIP-associated maintenance of neuronal survival in spinal cord cultures. Thus, we describe a potent VIP antagonist which interacts with two functionally distinct VIP receptors in the CNS. C1 NICHHD, DEV NEUROBIOL LAB,NEUROCHEM UNIT,BLD 36,ROOM 2A21, BETHESDA, MD 20892 USA. GEORGE WASHINGTON UNIV, SCH MED & HLTH SCI, DEPT BIOCHEM, WASHINGTON, DC 20052 USA. WEIZMANN INST SCI, DEPT ORGAN CHEM, IL-76100 REHOVOT, ISRAEL. NR 52 TC 147 Z9 149 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 EI 1521-0103 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUN PY 1991 VL 257 IS 3 BP 959 EP 966 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FQ593 UT WOS:A1991FQ59300006 PM 1646331 ER PT J AU FELDER, CC MA, AL LIOTTA, LA KOHN, EC AF FELDER, CC MA, AL LIOTTA, LA KOHN, EC TI THE ANTIPROLIFERATIVE AND ANTIMETASTATIC COMPOUND L651582 INHIBITS MUSCARINIC ACETYLCHOLINE RECEPTOR-STIMULATED CALCIUM INFLUX AND ARACHIDONIC-ACID RELEASE SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID AUTOCRINE MOTILITY FACTOR; SIGNAL TRANSDUCTION; L-CELLS; TRANSFORMATION; EXPRESSION; RESPONSES; TURNOVER; CYCLASE; MATRIX; CANCER AB L651582, a carboxyamide-amino-imidazole, was shown previously to have antiproliferative and antimetastatic properties at low micromolar concentrations; yet little is known about its cellular mechanism(s) of action. L651582 was tested for its ability to block receptor-stimulated calcium influx, arachidonic acid release, inositol phosphate and cyclic AMP (cAMP) generation. These signal transduction pathways are activated by muscarinic receptors transfected and expressed in Chinese hamster ovary cells. L651582 blocked muscarinic m5 receptor-stimulated Ca-45++ influx and release of arachidonic acid at low micromolar concentrations. Muscarinic receptor-stimulated release of arachidonic acid was shown previously to be dependent on calcium influx and not intracellular calcium release suggesting L651582 may be useful as calcium channel blocker. At low micromolar concentrations, L651582 had little effect on muscarinic m5 receptor-stimulated release of inositol phosphates or cAMP accumulation. Moreover, L651582 had little effect on muscarinic m2 receptor-mediated inhibition of forskolin-stimulated cAMP accumulation. Above 10-mu-M, L651582 inhibited all second messenger pathways tested and inhibited cell growth, suggesting its action may be less specific and toxic at these concentrations. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892. RP FELDER, CC (reprint author), NIMH,CELL BIOL LAB,BLDG 36,RM 3A-15,BETHESDA,MD 20892, USA. NR 25 TC 94 Z9 94 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 JUN PY 1991 VL 257 IS 3 BP 967 EP 971 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FQ593 UT WOS:A1991FQ59300007 PM 1646332 ER PT J AU LIN, WW LEE, CY CHUANG, DM AF LIN, WW LEE, CY CHUANG, DM TI ENDOTHELIN-INDUCED AND SARAFOTOXIN-INDUCED PHOSPHOINOSITIDE HYDROLYSIS IN CULTURED CEREBELLAR GRANULE CELLS - BIOCHEMICAL AND PHARMACOLOGICAL CHARACTERIZATION SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SMOOTH-MUSCLE CELLS; INOSITOL PHOSPHOLIPID HYDROLYSIS; BINDING-SITES; VASOCONSTRICTOR PEPTIDE; PHOSPHATE FORMATION; RECEPTOR AGONISTS; RABBIT AORTA; SPINAL-CORD; RAT ATRIA; BRAIN AB Endothelin (ET)-1,-2,-3, big ET-1 and sarafotoxin S6b (S6b) dose-dependently increased phosphoinositide (Pl) hydrolysis of 6- to 10-fold in cultured cerebellar granule cells prelabeled with [H-3] myoinositol. The Pl response elicited by ET-1 was dependent on the presence of extracellular Ca++, but was not reduced by organic (nisoldipine, nimodipine) or inorganic (Co++, Mn++) calcium channel blockers. Pretreatment of granule cells with tetrodotoxin or amiloride failed to affect the response to ET-1. Extracellular sodium depletion resulted in a marked increase in basal Pl turnover; however, the net increase of Pl turnover induced by ET-1 was unchanged. ET-induced Pl breakdown could be partially inhibited by short or long term treatment with phorbol dibutyrate but was unaffected by pertussis toxin. ET- and S6b-induced Pl turnover were dependent on the culturing time of granule cells, with the maximal response in a 4-day culture. The ET- and S6b-induced Pl turnover appeared to be additive to that induced by carbachol, histamine, norepinephrine, serotonin, glutamate and maitotoxin. However, the responses induced by ET and S6b were nonadditive. Prestimulation of cells with ET or S6b for 30 sec to 24 hr resulted in dramatic loss of the ability of ET and S6b to stimulate Pl hydrolysis, without affecting subsequent responsiveness induced by other stimuli, indicating homologous desensitization for ET- and S6b-induced responses. Moreover, our results further support the notion that ET and Sb6b act on the same population of receptors in cerebellar granule cells. C1 NIMH,BIOL PSYCHIAT BRANCH,MOLEC NEUROBIOL UNIT,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NATL TAIWAN UNIV,COLL MED,DEPT PHARMACOL,TAIPEI,TAIWAN. OI Lin, Wan Wan/0000-0002-3207-734X NR 60 TC 33 Z9 34 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 JUN PY 1991 VL 257 IS 3 BP 1053 EP 1061 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FQ593 UT WOS:A1991FQ59300020 PM 1646318 ER PT J AU CRAWLEY, JN FISKE, SM DURIEUX, C DERRIEN, M ROQUES, BP AF CRAWLEY, JN FISKE, SM DURIEUX, C DERRIEN, M ROQUES, BP TI CENTRALLY ADMINISTERED CHOLECYSTOKININ SUPPRESSES FEEDING THROUGH A PERIPHERAL-TYPE RECEPTOR MECHANISM SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID NUCLEUS TRACTUS SOLITARIUS; CCK-B-RECEPTORS; FOOD-INTAKE; BRAIN CHOLECYSTOKININ; RAT-BRAIN; HIGHLY POTENT; ENDOGENOUS CHOLECYSTOKININ; ANTAGONIST RADIOLIGAND; BINDING-SITES; A RECEPTORS AB Agonists and antagonists selective for the brain-type [cholecystokinin (CCK)-B] and the peripheral-type (CCK-A) CCK receptor were used to localize the site(s) of action at which CCK inhibits food consumption. BC 264, a highly selective CCK-B receptor agonist, did not decrease consumption of a palatable meal when administered either i.p. or into the lateral ventricles of the brain, whereas CCK decreased feeding when administered i.p. at the same doses. CCK decreased feeding when administered i.v.t. at a high dose, 5-mu-g. L-364,718, an antagonist selective for the CCK-A receptor, blocked completely the action of centrally administered CCK, whereas L-365,260, a selective CCK-B receptor antagonist, had no effect on the ability of centrally administered CCK to inhibit feeding. To estimate the quantity of i.v.t. administered CCK which reached the periphery, a tracer of radiolabeled [H-3]p-CCK8 ([H-3]CCK octapeptide sulfate), combined with unlabeled pCCK8 (5-mu-g) was administered i.c.t. Thirty minutes after administration, intact radiolabeled pCCK8 was extracted from the plasma and measured in the blood in nanomolar concentrations, exceeding the amounts of CCK octapeptide sulfate reported previously to be present in the plasma after a meal. Intraventricularly administered CCK thus appears to reduce feeding in the rat through a mechanism involving a CCK-A receptor subtype in the periphery. C1 UNIV PARIS 05,FAC PHARM,CNRS,UA 498,INSERM,U266,F-75270 PARIS 06,FRANCE. RP CRAWLEY, JN (reprint author), NIMH,EXPTL THERAPEUT BRANCH,BEHAV NEUROPHARMACOL UNIT,BLDG 10,ROOM 4N214,BETHESDA,MD 20892, USA. NR 62 TC 65 Z9 65 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 JUN PY 1991 VL 257 IS 3 BP 1076 EP 1080 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FQ593 UT WOS:A1991FQ59300023 PM 2046021 ER PT J AU HORAN, P DECOSTA, BR RICE, KC PORRECA, F AF HORAN, P DECOSTA, BR RICE, KC PORRECA, F TI DIFFERENTIAL ANTAGONISM OF U69,593- AND BREMAZOCINE-INDUCED ANTINOCICEPTION BY (-)-UPHIT - EVIDENCE OF KAPPA-OPIOID RECEPTOR MULTIPLICITY IN MICE SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID MOUSE VAS-DEFERENS; RAT-BRAIN MEMBRANES; GUINEA-PIG BRAIN; BINDING-SITES; OPIATE RECEPTOR; SELECTIVE LIGAND; DELTA-RECEPTORS; MU-RECEPTORS; MORPHINE; AGONISTS AB The effect of pretreatment with the kappa receptor nonequilibrium antagonist, (-)-UPHIT {1S, 2S-trans-2-isothiocyanato-4,5-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide}, on U69,593 {(5-alpha,7-alpha,8-beta)-(-)-N-methyl-N-(7-(1-pyrrolidinyl)-1-oxaspiro(4,5)dec-8-yl)benzeneacetamide}- and bremazocine-induced antinociception was examined in mice. Both U69,593 and bremazocine produced antinociception in the warm water tail-flick test after i.c.v. administration. Pretreatment with the kappa antagonist, nor-binaltorphimine, at doses shown not to affect [D-Ala2, NMePhe4, Gly-ol]enkephalin- (mu-agonist) or [D-Pen2, D-Pen5]enkephalin (delta-agonist)-induced antinociception, significantly attenuated the effects of U69,593 and bremazocine, suggesting actions of these agonists at kappa receptors. Furthermore, beta-funaltrxamine (mu antagonist) and ICI 174,864 {N,N,-diallyl-Tyr-(alpha-aminoisobutyric acid)2-Phe-Leu-OH} (delta antagonist), had no effect on U69,593 or bremazocine in this test providing further evidence of kappa receptor-mediated activity. Pretreatment with (-)-UPHIT produced no effect alone and a long-lasting (up to 48 hr) antagonism of U69,593, but not bremazocine, antinociception. The antagonist actions of (-)-UPHIT did not alter the antinociceptive effects of [D-Ala2, NMePhe4, Glyol]enkephalin or [D-Pen2, D-Pen5]enkephalin. These data suggest that (-)-UPHIT is a selective, long-lasting kappa antagonist which can differentially antagonize the antinocicieption produced by these two kappa agonists. These data provide evidence in vivo supportive of kappa receptor subtypes in the mouse, and suggest that (-)-UPHIT may be a useful probe for the exploration of kappa receptor heterogeneity. C1 UNIV ARIZONA,ARIZONA HLTH SCI CTR,DEPT PHARMACOL,TUCSON,AZ 85724. NIDDK,MED CHEM LAB,BETHESDA,MD. FU NIDA NIH HHS [DA 04248, DA 06284, DA 04285] NR 48 TC 65 Z9 65 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 JUN PY 1991 VL 257 IS 3 BP 1154 EP 1161 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FQ593 UT WOS:A1991FQ59300033 PM 1646325 ER PT J AU WHEELER, JJ SELTMANN, H MOTTEN, AG AF WHEELER, JJ SELTMANN, H MOTTEN, AG TI THE MODE OF ACTION OF FATTY ALCOHOLS ON LEAF TISSUE SO JOURNAL OF PLANT GROWTH REGULATION LA English DT Article AB The mode of action of a mixture of C-8 and C-10 fatty alcohols, formulated in polyoxyethylene (20) sorbitan mono-oleate (SMO) and used as an emulsion (FAE) to inhibit axillary bud (sucker) growth in tobacco production, was studied using infrared spectroscopy (NIR), photoacoustic spectroscopy (PAS), electrical resistance, and the ability of treated cells to reverse plasmolysis on leaf tissues from Nicotiana tabacum L. and other dicotyledonous species. NIR spectra showed that isolated cuticles were affected optically when treated with FAE, but did not dissolve. PAS absorbances in the UV of isolated cuticles and of epidermal peels were similar and showed that cuticles were homogeneous, unilamellar structures. In intact leaf segments, it was possible, over time using PAS absorbances in the visible region, to separate absorbance of the surface components (cuticle) from the absorption of chlorophyll and other subsurface components and to monitor the penetration by FAE into the leaf. Penetration of the FAE to the subcuticular cells took approximately 2 h. Electrical resistance measurements of FAE-treated isolated midveins of tobacco leaves decreased with time, indicating that the plasma membranes of the cells became leaky. The effect of FAE on plasma membranes of cells was confirmed with Elodea sp. where leaf cells after treatment with 1 and 5% FAE lost the ability with time to plasmolyze upon exposure to a 10% solution of Ca(NO3)2. The results of the various studies were interpreted to mean that at the labeled concentration (4-5%) for use in the control of axillary bud growth on decapitated tobacco, FAE passed through the cuticle without disrupting it. However, the plasma membranes of the subtending cells were altered so that, in time, bud tissues desiccated (appeared burned) and growth of the sucker was controlled. C1 USDA ARS,CROP RES LAB,OXFORD,NC 27565. NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. N CAROLINA STATE UNIV,DEPT BOT,RALEIGH,NC 27695. NR 9 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0721-7595 J9 J PLANT GROWTH REGUL JI J. Plant Growth Regul. PD SUM PY 1991 VL 10 IS 3 BP 129 EP 137 DI 10.1007/BF02279324 PG 9 WC Plant Sciences SC Plant Sciences GA GA086 UT WOS:A1991GA08600002 ER PT J AU HERTZMAN, PA FALK, H KILBOURNE, EM PAGE, S SHULMAN, LE AF HERTZMAN, PA FALK, H KILBOURNE, EM PAGE, S SHULMAN, LE TI THE EOSINOPHILIA-MYALGIA-SYNDROME - THE LOS-ALAMOS CONFERENCE SO JOURNAL OF RHEUMATOLOGY LA English DT Review DE EOSINOPHILIA; EOSINOPHILIA-MYALGIA SYNDROME; EOSINOPHILIC FASCIITIS ID L-TRYPTOPHAN INGESTION; ASSOCIATION; FASCIITIS; FEATURES; DISEASE; ILLNESS AB On June 12 and 13, 1990 the Los Alamos National Laboratory in cooperation with the New Mexico Department of Health and Environment, the Centers for Disease Control (CDC), the Food and Drug Administration (FDA), and the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH) hosted a conference on the eosinophilia-myalgia syndrome. Fifty presentations covered a variety of important issues which are summarized herein. C1 CTR DIS CONTROL,ATLANTA,GA 30333. US FDA,WASHINGTON,DC 20204. NIAMSD,BETHESDA,MD. RP HERTZMAN, PA (reprint author), LOS ALAMOS MED CTR,LOS ALAMOS,NM 87544, USA. NR 33 TC 47 Z9 47 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 JUN PY 1991 VL 18 IS 6 BP 867 EP 873 PG 7 WC Rheumatology SC Rheumatology GA FU454 UT WOS:A1991FU45400016 PM 1680191 ER PT J AU WEISS, GH HAVLIN, S AF WEISS, GH HAVLIN, S TI SOME PROPERTIES OF A FRACTAL-TIME CONTINUOUS-TIME RANDOM-WALK IN THE PRESENCE OF TRAPS SO JOURNAL OF STATISTICAL PHYSICS LA English DT Article DE RANDOM WALK; SURFACE TRAPPING; LASER RADIATION ID NEAREST-NEIGHBOR DISTANCES; PHOTON MIGRATION; SINGLE TRAP; DIFFUSION; DENSITY; TISSUE; MEDIA; MODEL AB The CTRW has often been applied to problems related to transport in a statistically homogeneous disordered medium, which means that there are no traps or reflecting boundaries to be found in the medium. Two physical applications, one to the migration of photons in a turbid medium and the second to the theory of diffusion-controlled reactions in a random medium, suggest that it might be useful to study properties of the CTRW, particularly as they refer to survival probability in the presence of a trap or a trapping surface. We calculate a number of these properties when the pausing-time density is asymptotically proportional to a stable law, i.e., psi(t) approximately T-alpha/t-alpha + 1 as (t/T) --> infinity, where 0 < alpha < 1. A forthcoming paper will establish the correspondence between properties of the CTRW and properties of random walkers on a fractal with trapping boundaries. C1 BAR ILAN UNIV, DEPT PHYS, IL-52100 RAMAT GAN, ISRAEL. RP NIH, BETHESDA, MD 20892 USA. NR 25 TC 8 Z9 8 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-4715 EI 1572-9613 J9 J STAT PHYS JI J. Stat. Phys. PD JUN PY 1991 VL 63 IS 5-6 BP 1005 EP 1018 DI 10.1007/BF01029995 PG 14 WC Physics, Mathematical SC Physics GA FV049 UT WOS:A1991FV04900013 ER PT J AU STEVEN, AC BAUER, AC BISHER, ME ROBEY, FA BLACK, LW AF STEVEN, AC BAUER, AC BISHER, ME ROBEY, FA BLACK, LW TI THE MATURATION-DEPENDENT CONFORMATIONAL CHANGE OF PHAGE-T4 CAPSID INVOLVES THE TRANSLOCATION OF SPECIFIC EPITOPES BETWEEN THE INNER AND THE OUTER CAPSID SURFACES SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article ID BACTERIOPHAGE-T4 PREHEAD PROTEINASE; MAJOR HEAD PROTEIN; ELECTRON-MICROGRAPHS; NUCLEOTIDE-SEQUENCE; POLYHEADS; TRANSFORMATION; FRAGMENT; CLEAVAGE; MUTANTS; LOCALIZATION C1 NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,DEPT BIOL CHEM,BALTIMORE,MD 21201. RP STEVEN, AC (reprint author), NIAMSD,STRUCT BIOL RES LAB,BLDG 6,ROOM 114,BETHESDA,MD 20892, USA. NR 39 TC 33 Z9 33 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD JUN PY 1991 VL 106 IS 3 BP 221 EP 236 DI 10.1016/1047-8477(91)90072-5 PG 16 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA FR232 UT WOS:A1991FR23200006 PM 1725126 ER PT J AU LEWIS, JF MARON, BJ CASTRO, O MOOSA, YA AF LEWIS, JF MARON, BJ CASTRO, O MOOSA, YA TI LEFT-VENTRICULAR DIASTOLIC FILLING ABNORMALITIES IDENTIFIED BY DOPPLER ECHOCARDIOGRAPHY IN ASYMPTOMATIC PATIENTS WITH SICKLE-CELL-ANEMIA SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID HYPERTROPHIC CARDIOMYOPATHY; MYOCARDIAL-INFARCTION; CARDIAC DYSFUNCTION; DISEASE; HEART; CHILDREN; RADIONUCLIDE; PERFORMANCE; PHYSIOLOGY; INDEXES AB To determine whether left ventricular diastolic abnormalities are an early feature of sickle cell anemia, indexes of diastolic filling were obtained with pulsed Doppler echocardiography in 30 consecutive patients with this disease (mean age 29 years; range 19 to 39) who had not experienced symptoms of heart failure and had normal left ventricular systolic function. Data were compared with those in 30 normal control subjects of similar ages. Seventeen (57%) of the 30 patients with sickle cell anemia had evidence of abnormal left ventricular diastolic filling. Six of these 17 patients had a Doppler pattern consistent with "restrictive" filling, characterized by reduced early diastolic deceleration time (< 110 ms) or an increased rate of decline of early flow velocity (EF slope > 7.4 m/s2), or both, as well as decreased late diastolic velocity-time integral (2.6 +/- 0.7 vs. 3.4 +/- 0.8 cm in normal subjects; p < 0.05). Another 11 patients showed a Doppler waveform consistent with impaired relaxation, characterized by prolonged deceleration time (> 166 ms) or reduced EF slope (< 3.8 m/s2), as well as increased late diastolic velocity-time integral (4.0 +/- 0.5 vs. 3.4 +/- 0.8 cm in normal subjects; p = 0.03). This Doppler echocardiographic analysis demonstrates that left ventricular diastolic filling patterns are altered in patients with sickle cell anemia and that these diastolic abnormalities may be present in the absence of symptoms of heart failure. These abnormal patterns suggest an intrinsic myocardial abnormality in patients with sickle anemia and may prove to be early markers of cardiac disease. C1 HOWARD UNIV,COLL MED,DEPT MED,DIV CARDIOVASC DIS,WASHINGTON,DC 20001. HOWARD UNIV,COLL MED,DEPT MED,CTR SICKLE CELL,WASHINGTON,DC 20001. NHLBI,BETHESDA,MD 20892. FU NHLBI NIH HHS [HL01984] NR 39 TC 35 Z9 35 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUN PY 1991 VL 17 IS 7 BP 1473 EP 1478 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA FQ229 UT WOS:A1991FQ22900005 PM 2033179 ER PT J AU TYLENDA, CA ROBERTS, MW ELIN, RJ LI, SH ALTEMUS, M AF TYLENDA, CA ROBERTS, MW ELIN, RJ LI, SH ALTEMUS, M TI BULIMIA-NERVOSA - ITS EFFECT ON SALIVARY CHEMISTRY SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID DIFFERENT AGE-GROUPS; EATING DISORDERS; ANOREXIA-NERVOSA; FLOW-RATE; HYPERAMYLASEMIA AB Erosion of the dental hard tissues and enlarged parotid and submandibular saliva glands are commonly associated with bulimia nervosa. In 15 patients and controls, no significant difference was detected in the concentrations of potassium, chloride, calcium, urea nitrogen or albumin. There was also no evidence of olfactory dysfunction. C1 UNIV N CAROLINA,SCH DENT,DEPT PEDIAT DENT,CHAPEL HILL,NC 27514. NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,BETHESDA,MD 20892. NIMH,MED STAFF,BETHESDA,MD 20892. NIDR,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,BETHESDA,MD 20892. RP TYLENDA, CA (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,1390 PILLARD DR,ROOM 240B,ROCKVILLE,MD 20850, USA. NR 17 TC 19 Z9 19 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 JUN PY 1991 VL 122 IS 7 BP 37 EP 41 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA FQ068 UT WOS:A1991FQ06800010 PM 2066518 ER PT J AU OLIVER, RC BROWN, LJ LOE, H AF OLIVER, RC BROWN, LJ LOE, H TI VARIATIONS IN THE PREVALENCE AND EXTENT OF PERIODONTITIS SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article AB A national survey of employed adults showed a decrease in the extent and severity of periodontal disease in comparison with findings from earlier studies. Using data from that survey, this report evaluates the association of socioeconomic factors-race, education, income and dental insurance, as well as most recent dental visit-with the prevalence and extent of periodontal disease. Periodontitis was more prevalent and usually more extensive in persons who are black, have less education or had not seen a dentist in three or more years. Having dental insurance was not associated with better periodontal health. C1 NIDR,ANALYT STUDIES BRANCH,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,BETHESDA,MD 20892. RP OLIVER, RC (reprint author), UNIV MINNESOTA,SCH DENT,SERV PERIODONTOL & HLTH RES,17-164 MOOS TOWER 515 DELAWARE ST SE,MINNEAPOLIS,MN 55455, USA. NR 12 TC 72 Z9 73 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 JUN PY 1991 VL 122 IS 7 BP 43 EP 48 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA FQ068 UT WOS:A1991FQ06800011 PM 2066519 ER PT J AU GOLDSTEIN, DS CANNON, RO QUYYUMI, A CHANG, P DUNCAN, M BRUSH, JE EISENHOFER, G AF GOLDSTEIN, DS CANNON, RO QUYYUMI, A CHANG, P DUNCAN, M BRUSH, JE EISENHOFER, G TI REGIONAL EXTRACTION OF CIRCULATING NOREPINEPHRINE, DOPA, AND DIHYDROXYPHENYLGLYCOL IN HUMANS SO JOURNAL OF THE AUTONOMIC NERVOUS SYSTEM LA English DT Article DE DIHYDROXYPHENYLGLYCOL; DOPA; SYMPATHETIC NERVOUS SYSTEM; NOREPINEPHRINE; EPINEPHRINE; KINETICS ID NERVOUS-SYSTEM ACTIVITY; PLASMA DIHYDROXYPHENYLALANINE; PHYSIOLOGICAL SIGNIFICANCE; ESSENTIAL-HYPERTENSION; NEURONAL REMOVAL; TOTAL-BODY; CATECHOLAMINES; NORADRENALINE; KINETICS; RAT AB Dihydroxyphenylglycol (DHPG) is the main intraneuronal metabolite of the sympathetic neurotransmitter, norepinephrine (NE), and dihydroxyphenylalanine (DOPA) the immediate product of the rate-limiting step in catecholamine biosynthesis. Simultaneous measurements of regional rates of appearance (spillovers) of NE, DOPA, and DHPG in plasma have the potential to provide unique information about aspects of sympathoneural function but have not actually been measured in humans. In the present study, spillovers of DHPG, DOPA, and NE in the heart, head, leg, and lungs, were estimated from regional extraction fractions of infused [H-3]-l-NE, DHPG, and [(C6)-C-13]DOPA or unlabelled DOPA in humans during cardiac catheterization. There was little cardiac extraction of DHPG (7 +/- SEM 2%) or DOPA (8 +/- 4%) but substantial extraction of NE (69 +/- 4%). Values for cardiac spillover of DHPG and DOPA therefore were similar to values for the arteriovenous increment times plasma flow (arteriovenous production rate). whereas the cardiac spillover of NE averaged about 7-times the NE arteriovenous production rate. Cardiac DHPG spillover (28 +/- 3 ng/min) exceeded the spillovers of NE (9 +/- 2 ng/min) and DOPA (15 +/- 4 ng/min). In contrast, cranial DOPA spillover (159 ng/min) exceeded those of NE and DHPG by 8- and 2-fold and accounted for about 1/10 of the total spillover of DOPA into arterial plasma. In the femoral vascular bed, arteriovenous production rates of NE and DHPG were unrelated to femoral spillovers of NE and DHPG. Arterial and regional clearances of [(C6)-C-13]DOPA were similar to those of unlabelled DOPA. The results suggest that (1) endogenous NE, DOPA, and DHPG all are released into the bloodstream by the heart, head, and limbs of humans; (2) DHPG and DOPA are not co-released with NE; (3) cardiac arteriovenous production rates of DOPA and DHPG can be used to indicate cardiac spillover of these catechols, whereas the cardiac NE arteriovenous production rate substantially underestimates cardiac NE spillover; and (4) estimates of limb spillover of NE and DHPG require concurrent measurements of the corresponding regional clearances. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. LEIDEN UNIV,DEPT MED,2300 RA LEIDEN,NETHERLANDS. BOSTON UNIV HOSP,CARDIOL SECT,BOSTON,MA 02218. BAKER MED RES INST,PRAHRAN,VIC 3181,AUSTRALIA. RP GOLDSTEIN, DS (reprint author), NINCDS,CLIN NEUROSCI BRANCH,BLDG 10,ROOM 7N238,BETHESDA,MD 20892, USA. NR 38 TC 49 Z9 49 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-1838 J9 J AUTONOM NERV SYST JI J. Auton. Nerv. Syst. PD JUN PY 1991 VL 34 IS 1 BP 17 EP 35 DI 10.1016/0165-1838(91)90005-N PG 19 WC Neurosciences SC Neurosciences & Neurology GA FT468 UT WOS:A1991FT46800004 PM 1940014 ER PT J AU REED, E JACOB, J BRAWLEY, O AF REED, E JACOB, J BRAWLEY, O TI MEASURES OF RENAL-FUNCTION IN PATIENTS WITH CISPLATIN-RELATED CHRONIC RENAL-DISEASE SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE CISPLATIN; RENAL FUNCTION; CHEMOTHERAPY; IMMUNOTHERAPY AB Twenty-seven patients with advanced stage refractory ovarian cancer were studied to determine if chronic stable cisplatin-related renal dysfunction was present. Medical histories were examined to determine the types of therapy previously received as well as the total previous platinum doses received that ranged from 200 to 2 100 mg/m2. Standard assessments of renal function were made prior to administering current chemotherapy or immunotherapy to the patient, which included 24-hour creatinine clearance, serum creatinine, and blood urea nitrogen (BUN). For patients with a 24-hour creatinine clearance of less than 60 mL/minute, serum creatinine was highly variable (range: 0.9 to 2.0 mg/dL) and was not related to the degree of diminution in the 24-hour creatinine clearance value. Conversely, for patients with a serum creatinine of less than 1.5, the 24-hour creatinine clearance values varied by almost three-fold, ranging between 46 and 120 mL/minute. Two patients with serum creatinines of less than 1 had creatinine clearances of less than 50 mL per minute. Similarly, BUN measurements did not correlate with 24-hour creatinine clearance values, and the 24-hour creatinine clearance value was not related to the total cumulative platinum dose. We conclude that patients who receive substantive doses of cisplatin may experience chronic stable cisplatin-related renal dysfunction and that serum creatinine cannot be relied on the assess the degree of renal compromise. In such patients, we recommend that the 24-hour creatinine clearance value should be used when medical management is influenced by renal function. RP REED, E (reprint author), NCI,MED BRANCH,BLDG 10,RM 12N226,BETHESDA,MD 20892, USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD JUN PY 1991 VL 83 IS 6 BP 522 EP 526 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA FR073 UT WOS:A1991FR07300011 PM 1865503 ER PT J AU MCCUTCHEN, CW AF MCCUTCHEN, CW TI CONVOLUTION RELATION WITHIN THE 3-DIMENSIONAL DIFFRACTION IMAGE SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Article AB The amplitude in the image of a point source is (a constant times) the three-dimensional Fourier transform of the lens pupil, i.e., of the amplitude distribution of the converging waves in angle space. If the three-dimensional pupil has axial symmetry, it can be factored into a spherical shell and a one-dimensional function of distance along the axis. The amplitude in the image is given by the convolution of the Fourier transforms of the factors. On the axis, the amplitude is the Fourier transform of the one-dimensional function. Therefore the amplitude anywhere in the image is the convolution of the amplitude on the axis and the Fourier transform of the spherical shell. RP MCCUTCHEN, CW (reprint author), NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892, USA. NR 12 TC 8 Z9 8 U1 0 U2 2 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 SN 0740-3232 J9 J OPT SOC AM A JI J. Opt. Soc. Am. A-Opt. Image Sci. Vis. PD JUN PY 1991 VL 8 IS 6 BP 868 EP 870 DI 10.1364/JOSAA.8.000868 PG 3 WC Optics SC Optics GA FN002 UT WOS:A1991FN00200005 PM 2061727 ER PT J AU GULAKOWSKI, RJ MCMAHON, JB STALEY, PG MORAN, RA BOYD, MR AF GULAKOWSKI, RJ MCMAHON, JB STALEY, PG MORAN, RA BOYD, MR TI A SEMIAUTOMATED MULTIPARAMETER APPROACH FOR ANTI-HIV DRUG SCREENING SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE ANTI-HIV ASSAY; FLUORESCENCE; DRUG SCREENING ID ASSAY AB We are implementing a series of complementary assays for initial follow-up confirmation and prioritization of new active anti-HIV compounds identified by the U.S. National Cancer Institute's large-scale in vitro primary anti-HIV screen. Two different kinds of cellular viability assays, in addition to specific assays for total cellular DNA content, supernatant reverse transcriptase activity, p24 core antigen production and the synthesis of infectious HIV virions are all performed from a single well of a 96-well microtiter plate containing human host cells infected with HIV. Antiviral activities of several known prototype HIV inhibitors including 3'-azido,3'-deoxythymidine, 2',3'-dideoxycytidine, dextran sulfate and phorbol myristate acetate were compared in these multiparameter assays as a means of validation. Procedures to automate the method optimally, as well as to maximize the safety of the technicians working with HIV and HIV-infected cells have been emphasized. The resulting semiautomated, highly reproducible battery of assays yields a maximum amount of antiviral and cytotoxicity information from a minimum amount of sample. This is especially crucial when analyzing new synthetic compounds and natural product extracts or fractions where the available amounts of sample may be very limited. C1 NCI,FREDERICK CANC RES & DEV CTR,DRUG DISCOVERY RES & DEV LAB,BLDG 1052,ROOM 121,FREDERICK,MD 21702. PROGRAM RESOURCES INC,FREDERICK,MD. NR 13 TC 116 Z9 117 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD JUN PY 1991 VL 33 IS 1-2 BP 87 EP 100 DI 10.1016/0166-0934(91)90010-W PG 14 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA FZ629 UT WOS:A1991FZ62900009 PM 1719015 ER PT J AU HORVAT, RT WOOD, C JOSEPHS, SF BALACHANDRAN, N AF HORVAT, RT WOOD, C JOSEPHS, SF BALACHANDRAN, N TI TRANSACTIVATION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS PROMOTER BY HUMAN HERPESVIRUS-6 (HHV-6) STRAIN-GS AND STRAIN-Z-29 IN PRIMARY HUMAN LYMPHOCYTES-T AND IDENTIFICATION OF TRANSACTIVATING HHV-6(GS) GENE FRAGMENTS SO JOURNAL OF VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; CHLORAMPHENICOL ACETYLTRANSFERASE; TYPE-1 REPLICATION; TRANS-ACTIVATION; HTLV-III; CELLS; AIDS; EXPRESSION; INFECTION; HIV-1 AB Human herpesvirus 6 (HHV-6) can activate the human immunodeficiency virus (HIV) promoter and accelerate cytopathic effects in HIV-infected human T cells. This study examines the regions of the HIV promoter required for HHV-6 transactivation in a heterogeneous population of primary human T lymphocytes with or without antigenic stimulation. Two different strains of HHV-6, GS and Z29, transactivated the HIV promoter. The GS strain transactivated the promoter in both stimulated and resting T cells, while the Z29 strain increased HIV promoter activity only in stimulated T cells. Three DNA clones containing HHV-6(GS) genomic fragments transactivated the HIV promoter in cotransfected T cells. A 21.4-kb DNA clone, pZVB70, showed the highest transactivating ability, while two other DNA fragments, pZVB10 (6.2 kb) and pZVH14 (8.7 kb), showed lower activity. One of these clones, pZVH14, activated the HIV promoter construct containing a mutation in the NFkB site. However, this mutated NFkB promoter was not transactivated during HHV-6(GS) infection or after cotransfection with pZVB70 or pZVB10. These data indicate that the NFkB sites of the HIV promoter are essential for its transactivation during HHV-6(GS) infection. By increasing HIV promoter activity in primary T lymphocytes, HHV-6 may consequently increase HIV replication, leading to an increase in the cytopathic effect on coinfected human T cells. C1 UNIV KANSAS,MED CTR,DEPT MICROBIOL MOLEC GENET & IMMUNOL,KANSAS CITY,KS 66103. UNIV KANSAS,DEPT MICROBIOL,LAWRENCE,KS 66045. NCI,BETHESDA,MD 20892. FU NIAID NIH HHS [AI 24224, AI30355, AI 24115] NR 42 TC 48 Z9 50 U1 0 U2 1 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 JUN PY 1991 VL 65 IS 6 BP 2895 EP 2902 PG 8 WC Virology SC Virology GA FM165 UT WOS:A1991FM16500016 PM 1851861 ER PT J AU DRYSDALE, CM PAVLAKIS, GN AF DRYSDALE, CM PAVLAKIS, GN TI RAPID ACTIVATION AND SUBSEQUENT DOWN-REGULATION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 PROMOTER IN THE PRESENCE OF TAT - POSSIBLE MECHANISMS CONTRIBUTING TO LATENCY SO JOURNAL OF VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; MESSENGER-RNA; TRANS-ACTIVATION; GENE-EXPRESSION; TRANSCRIPTIONAL ACTIVATION; HTLV-III; EUKARYOTIC CELLS; T-CELLS; HIV-1; PROTEIN AB The mechanism of induction of gene expression of the human immunodeficiency virus type 1 long terminal repeat (LTR) by the Tat transactivator protein was studied in a cell fusion assay. Tat causes a rapid activation of both transcription from the LTR and accumulation of hybrid LTR-chloramphenicol acetyltransferase mRNAs. Approximately 4 h after induction by Tat, expression from the LTR promoter is down-regulated, resulting in a decrease in the accumulation of LTR mRNA. This down-regulation of expression occurs in the continued presence of Tat. Protein synthesis inhibitors can block this down-regulation; therefore, the postinduction repression of expression is dependent upon de novo protein synthesis. We propose that a labile cellular protein(s) is responsible for the low levels of human immunodeficiency virus type 1 expression, possibly contributing to the establishment of a latent state of viral expression. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 64 TC 31 Z9 31 U1 0 U2 1 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 JUN PY 1991 VL 65 IS 6 BP 3044 EP 3051 PG 8 WC Virology SC Virology GA FM165 UT WOS:A1991FM16500034 PM 2033665 ER PT J AU LARRALDE, G LI, BG KAPIKIAN, AZ GORZIGLIA, M AF LARRALDE, G LI, BG KAPIKIAN, AZ GORZIGLIA, M TI SEROTYPE-SPECIFIC EPITOPE(S) PRESENT ON THE VP8-SUBUNIT OF ROTAVIRUS VP4-PROTEIN SO JOURNAL OF VIROLOGY LA English DT Article ID NEUTRALIZATION EPITOPES; MONOCLONAL-ANTIBODIES; CLEAVAGE REGION; VP3; IDENTIFICATION; PROTEIN; SA11; INFECTIVITY; GENES AB cDNA clones representing the VP8 and VP5 subunits of VP4 of symptomatic human rotavirus strain KU (VP7 serotype 1 and VP4 serotype 1A) or DS-1 (VP7 serotype 2 and VP4 serotype 1B) or asymptomatic human rotavirus strain 1076 (VP7 serotype 2 and VP4 serotype 2) were constructed and inserted into the pGEMEX-1 plasmid and expressed in Escherichia coli. Immunization of guinea pigs with the VP8 or VP5 protein of each strain induced antibodies that neutralized the rotavirus from which the VP4 subunits were derived. In a previous study (M. Gorziglia, G. Larralde, A. Z. Kapikian, and R. M. Chanock, Proc. Natl. Acad. Sci. USA 87:7155-7159, 1990), three distinct serotypes and one subtype of VP4 outer capsid protein were identified among 17 human rotavirus strains that had previously been assigned to five distinct VP7 serotypes. The results obtained by cross-immunoprecipitation and by neutralization assay with antisera to the VP8- and VP5-expressed proteins suggest that the VP8 subunit of VP4 contains the major antigenic site(s) responsible for serotype-specific neutralization of rotavirus via VP4, whereas the VP5 subunit of VP4 is responsible for much of the cross-reactivity observed among strains that belong to different VP4 serotypes. RP LARRALDE, G (reprint author), NIAID,INFECT DIS LAB,BETHESDA,MD 20892, USA. NR 22 TC 59 Z9 63 U1 1 U2 1 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 JUN PY 1991 VL 65 IS 6 BP 3213 EP 3218 PG 6 WC Virology SC Virology GA FM165 UT WOS:A1991FM16500053 PM 1709699 ER PT J AU LAYNE, SP MERGES, MJ SPOUGE, JL DEMBO, M NARA, PL AF LAYNE, SP MERGES, MJ SPOUGE, JL DEMBO, M NARA, PL TI BLOCKING OF HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION DEPENDS ON CELL-DENSITY AND VIRAL STOCK AGE SO JOURNAL OF VIROLOGY LA English DT Article ID RECOMBINANT SOLUBLE CD4; NEUTRALIZING MONOCLONAL-ANTIBODY; AIDS-RELATED COMPLEX; ENVELOPE GLYCOPROTEIN; SYNCYTIUM FORMATION; HIV INFECTIVITY; HTLV-III/LAV; T4 ANTIGEN; GP120; TYPE-1 AB Quantitative infectivity assays were used to study how the blocking activity of soluble CD4 (sCD4) is affected by sCD4 concentration, target cell density, and viral stock age. During incubation with 20 nM sCD4, human immunodeficiency virus type 1 (HIV-1) stocks underwent irreversible inactivation. In contrast, inactivation with 2 nM sCD4 was almost entirely reversible. At lower sCD4 concentrations (less-than-or-equal-to 2 nM) and target cell densities of 6.25 x 10(4) ml-1, sCD4 blocking activity for HIV-1 gave a gp120-sCD4 association constant (K(assoc)) of 1.7 x 10(9) M-1, which agrees with chemical measurements. At the higher density of 1.6 x 10(7) cells ml-1, however, the blocking activity was 20-fold less. During incubation of HIV-1 stock optimized for infectivity by rapid harvest, sCD4 blocking activity increased 20-fold during a 3-h window. These results show that competitive blocking activity depends strongly on target cell density and virion age. Thus, unappreciated variations in HIV stocks and assay conditions may hinder comparisons of blockers from laboratory to laboratory, and the age of HIV challenge stocks may influence studies of drug and vaccine efficacy. The results also suggest that blocking of viral particles in lymphoid compartments will require very high competitive blocker concentrations, which may explain the refractory outcomes from sCD4-based drug trials in humans. C1 NCI,FREDERICK CANC RES & DEV CTR,TUMOR CELL BIOL SECT,VIRUS BIOL SECT,FREDERICK,MD 21701. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. RP LAYNE, SP (reprint author), UNIV CALIF LOS ALAMOS SCI LAB,DIV THEORET,THEORET BIOL & BIOPHYS GRP,LOS ALAMOS,NM 87544, USA. RI Dembo, Micah/C-2755-2013 NR 64 TC 56 Z9 56 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 JUN PY 1991 VL 65 IS 6 BP 3293 EP 3300 PG 8 WC Virology SC Virology GA FM165 UT WOS:A1991FM16500062 PM 1674549 ER PT J AU LODMELL, DL SUMNER, JW ESPOSITO, JJ BELLINI, WJ EWALT, LC AF LODMELL, DL SUMNER, JW ESPOSITO, JJ BELLINI, WJ EWALT, LC TI RACCOON POXVIRUS RECOMBINANTS EXPRESSING THE RABIES VIRUS NUCLEOPROTEIN PROTECT MICE AGAINST LETHAL RABIES VIRUS-INFECTION SO JOURNAL OF VIROLOGY LA English DT Note ID MONOCLONAL-ANTIBODIES; VACCINIA VIRUS; GLYCOPROTEIN; CELLS; RIBONUCLEOPROTEIN; HEMAGGLUTININ; VACCINATION; MECHANISMS; ANTIGENS; IMMUNITY AB Raccoon poxvirus (RCN) recombinants expressing the rabies virus internal structural nucleoprotein (RCN-N) protected A/WySnJ mice against a lethal challenge with street rabies virus (SRV). Maximum survival was achieved following vaccination by tail scratch and footpad (FP) SRV challenge. RCN-N-vaccinated mice inoculated in the FP with SRV were resistant to infection for at least 54 weeks postvaccination. Protection was also elicited by RCN recombinants expressing the rabies virus glycoprotein (RCN-G). Vaccination with RCN-G evoked rabies virus neutralizing antibody. Rabies virus neutralizing antibody was not detected in RCN-N-vaccinated mice prior to or following SRV infection. Radioimmunoprecipitation assays showed that sera from RCN-N-vaccinated mice which survived SRV infection did not contain antibody to SRV structural protein G, M, or NS. The mechanism(s) of N-induced resistance appears to correlate with the failure of peripherally inoculated SRV to enter the central nervous system (CNS). Support for this correlation with resistance was documented by the observations that SRV-inoculated RCN-N-vaccinated mice did not develop clinical signs of CNS rabies virus infection, infectious SRV was not detected in the spinal cord or brain following FP challenge, and all RCN-N-vaccinated mice died following direct intracranial infection of the CNS with SRV. These results suggest that factors other than anti-G neutralizing antibody are important in resistance to rabies virus and that the N protein should be considered for incorporation with the G protein in recombinant vaccines. C1 CTR DIS CONTROL,CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,ATLANTA,GA 30333. RP LODMELL, DL (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840, USA. NR 37 TC 33 Z9 33 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 JUN PY 1991 VL 65 IS 6 BP 3400 EP 3405 PG 6 WC Virology SC Virology GA FM165 UT WOS:A1991FM16500080 PM 2033678 ER PT J AU BATTLES, AH KNAPKA, JT LEWIS, L LANG, MT GRUENDEL, DJ AF BATTLES, AH KNAPKA, JT LEWIS, L LANG, MT GRUENDEL, DJ TI HIGH-MOISTURE DIET FOR LABORATORY RATS - NUTRIENT ANALYSIS, GROWTH, AND ORGAN WEIGHTS SO LABORATORY ANIMAL SCIENCE LA English DT Article AB A diet (KSC-25) to be sterilized by irradiation was formulated to contain 66% moisture and to provide the required nutrients for growing rats. Analyses of the irradiated dry diet provided data to evaluate its nutrient content. The diet was evaluated for its ability to supply all nutrients, including water, required by immature rats. Sixteen Sprague-Dawley rats were fed the high-moisture diet with or without access to a water bottle. Rats (n = 16) fed an irradiated purified diet in a meal form with access to a water bottle were the control animals. Feed efficiency, food and water consumption, and growth rate data were collected during the 28-day study. Organ weights were collected on day 28. The test diet met or exceeded the National Research Council (NRC) estimated nutritional requirements for immature laboratory rats. The 66% moisture KSC-25 diet provided all nutrients, including water, required by weanling male Sprague-Dawley rats for growth equivalent to the established purified diet. C1 NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BETHESDA,MD 20892. RP BATTLES, AH (reprint author), BIONET CORP,NASA,BIOMED OPERAT & RES OFF,KENNEDY SPACE CTR,FL 32899, USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD JUN PY 1991 VL 41 IS 3 BP 237 EP 241 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA GF778 UT WOS:A1991GF77800004 PM 1658461 ER PT J AU BATTLES, AH KNAPKA, JT STEVENS, BR LEWIS, L LANG, MT GRUENDEL, DJ AF BATTLES, AH KNAPKA, JT STEVENS, BR LEWIS, L LANG, MT GRUENDEL, DJ TI HIGH-MOISTURE DIET FOR LABORATORY RATS - COMPLETE BLOOD COUNTS, SERUM BIOCHEMICAL VALUES, AND INTESTINAL ENZYME-ACTIVITY SO LABORATORY ANIMAL SCIENCE LA English DT Article ID SUCRASE; LIVER AB Rats were fed an irradiated high-moisture diet (KSC-25) with or without access to a water bottle. Physiologic values were compared between these two groups and a group of rats fed a purified diet. Hematologic and serum biochemical values, urine specific gravity, and intestinal enzyme activities were determined from samples collected from the three groups of rats. Sprague Dawley rats (n = 32) fed the irradiated high-moisture diet with or without a water bottle were the test animals. Rats (n = 16) fed an irradiated purified diet and water provided via a water bottle were the control group. The purified diet formulation, modified AIN-76A, is a commonly used purified diet for laboratory rodents. All rats remained alert and healthy throughout the study. A comparison of the physiologic values of rats in this study with reported normal values indicated that all of the rats in the study were in good health. Significant differences (P < 0.05) of the physiologic values from each rat group are reported. C1 NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BETHESDA,MD 20892. UNIV FLORIDA,COLL MED,DEPT PHYSIOL,GAINESVILLE,FL 32610. RP BATTLES, AH (reprint author), BIONET CORP,NASA,BIOMED OPERAT & RES OFF,KENNEDY SPACE CTR,FL 32899, USA. NR 18 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD JUN PY 1991 VL 41 IS 3 BP 242 EP 245 PG 4 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA GF778 UT WOS:A1991GF77800005 PM 1658462 ER PT J AU MITCHELL, SW MBOUP, S MINGLE, J SAMBE, D TUKEI, P MILENGE, K NYAMONGO, J MUBARAK, OK SANKALE, JL HANSON, DS QUINN, TC AF MITCHELL, SW MBOUP, S MINGLE, J SAMBE, D TUKEI, P MILENGE, K NYAMONGO, J MUBARAK, OK SANKALE, JL HANSON, DS QUINN, TC TI FIELD-EVALUATION OF ALTERNATIVE HIV TESTING STRATEGY WITH A RAPID IMMUNOBINDING ASSAY AND AN AGGLUTINATION ASSAY SO LANCET LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; LATEX AGGLUTINATION; SCREENING ASSAYS; ANTIBODY AB A rapid immunobinding assay ('HIVCHEK', Ortho) and an agglutination assay ('Serodia-HIV', Fujirebio) were evaluated as an alternative to enzyme-linked immunosorbent assay (ELISA) and western blot under field conditions in Africa for detection of antibody to human immunodeficiency virus (HIV). 7106 specimens were tested at 25 laboratories in Kenya, Ghana, Senegal, and Zaire. HIVCHEK was used as a screening test, and serodia-HIV as a supplemental test to evaluate these assays in an alternative testing strategy to the standard ELISA/western blot testing procedure. In each country, HIVCHEK was more sensitive and specific than ELISA when compared with western blot. The sensitivity of HIVCHEK ranged from 87.0 to 96.3% and the specificity from 99.0 to 100%. The sensitivity and specificity of serodia-HIV ranged from 85 to 98% and from 88 to 98%, respectively. The sensitivity and specificity were affected by the presence of HIV-2 in Ghana and Senegal. Overall, with an HIV-1 prevalence of 14.8% in Kenya and 22.5% in Zaire, the sensitivities of the alternative strategy were 96.4% and 91.4%, the specificities 99.6% and 100%, the positive predictive values 97.6% and 100%, and the negative predictive values 99.3% and 97.9% for Kenya and Zaire, respectively. With this testing format there was an estimated average cost saving of up to 82% over the conventional strategy with ELISA/western blot. This procedure constitutes a reasonable alternative to the standard ELISA/western blot combination. C1 UNIV DAKAR,DAKAR,SENEGAMBIA. UNIV GHANA,SCH MED,ACCRA,GHANA. SOINS SANTE PRIMAIRES MILIEU RURALE,KINSHASA,ZAIRE. KENYA GOVT MED RES CTR,VIRUS RES CTR,NAIROBI,KENYA. NATL PUBL,HLTH LAB SERV,NAIROBI,KENYA. NOGUCHI MEM INST MED RES,ACCRA,GHANA. HOP LE DANTEC,DAKAR,SENEGAMBIA. NIAID,BETHESDA,MD 20892. RP MITCHELL, SW (reprint author), FAMILY HLTH INT,POB 13950,RES TRIANGLE PK BRANCH,DURHAM,NC 27709, USA. NR 9 TC 36 Z9 36 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 JUN 1 PY 1991 VL 337 IS 8753 BP 1328 EP 1331 DI 10.1016/0140-6736(91)92991-A PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA FP084 UT WOS:A1991FP08400014 PM 1674306 ER PT J AU JOSEPHS, SF HENRY, B BALACHANDRAN, N STRAYER, D PETERSON, D KOMAROFF, AL ABLASHI, DV AF JOSEPHS, SF HENRY, B BALACHANDRAN, N STRAYER, D PETERSON, D KOMAROFF, AL ABLASHI, DV TI HHV-6 REACTIVATION IN CHRONIC FATIGUE SYNDROME SO LANCET LA English DT Letter ID HBLV; VIRUS C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. UNIV NEVADA,DEPT MICROBIOL,RENO,NV 89557. UNIV KANSAS,SCH MED,DEPT MICROBIOL & IMMUNOL,LAWRENCE,KS 66045. HAHNEMANN UNIV,DEPT NEOPLAST DIS,PHILADELPHIA,PA 19102. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV GEN MED,BOSTON,MA 02115. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 9 TC 50 Z9 50 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 JUN 1 PY 1991 VL 337 IS 8753 BP 1346 EP 1347 DI 10.1016/0140-6736(91)93018-5 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA FP084 UT WOS:A1991FP08400034 PM 1674318 ER PT J AU PARSEGIAN, VA RAND, RP AF PARSEGIAN, VA RAND, RP TI ON MOLECULAR PROTRUSION AS THE SOURCE OF HYDRATION FORCES SO LANGMUIR LA English DT Note ID DNA DOUBLE HELICES; PHOSPHOLIPID-BILAYERS; MEMBRANES; SURFACES; WATER; CHOLESTEROL; SYSTEMS C1 BROCK UNIV,ST CATHARINES L2S 3A1,ONTARIO,CANADA. RP PARSEGIAN, VA (reprint author), NIH,BETHESDA,MD 20892, USA. NR 26 TC 47 Z9 47 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0743-7463 J9 LANGMUIR JI Langmuir PD JUN PY 1991 VL 7 IS 6 BP 1299 EP 1301 DI 10.1021/la00054a047 PG 3 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA FT336 UT WOS:A1991FT33600047 ER PT J AU SANTINI, G CONGIU, AM COSER, P CHISESI, T PORCELLINI, A SERTOLI, R CONTU, A VINANTE, O PIERLUIGI, D VITALE, V RUBAGOTTI, A ORCAMO, P RIZZOLI, V AF SANTINI, G CONGIU, AM COSER, P CHISESI, T PORCELLINI, A SERTOLI, R CONTU, A VINANTE, O PIERLUIGI, D VITALE, V RUBAGOTTI, A ORCAMO, P RIZZOLI, V TI AUTOLOGOUS BONE-MARROW TRANSPLANTATION FOR ADULT ADVANCED STAGE LYMPHOBLASTIC LYMPHOMA IN 1ST CR - A STUDY OF THE NHLCSG SO LEUKEMIA LA English DT Article; Proceedings Paper CT 2ND VICENZA INTERNATIONAL WORKSHOP OF HEMATOLOGY : NEW INSIGHTS IN LYMPHOMAS CY MAY 29-31, 1991 CL VICENZE, ITALY SP ITALIAN SOC HEMATOL ID NON-HODGKINS LYMPHOMA; TOTAL-BODY IRRADIATION; COMPLETE REMISSION; MALIGNANT-LYMPHOMA; THERAPY; LEUKEMIA AB Fourty successive adult patients with lymphoblastic lymphoma entered a study of sequential chemotherapy consisting of an intensive LSA-L2-type protocol to induce first complete remission. Twenty-one patients in first CR (median age 24 years, range 15-43), after receiving a conditioning regimen consisting of cyclophosphamide and total body irradiation, underwent autologous bone marrow transplantation. At this time fourtheen patients are alive and well 5-72 months post-transplant (median follow-up 58 months) with an actuarial disease free survival of 66%. These early results suggest that high-dose chemoradiotherapy followed by autologous bone marrow transplantation may improve long-term disease free survival in advanced stage adult lymphoblastic lymphoma. C1 OSPED CIVILE,DIV HEMATOL,VICENZA,ITALY. OSPED CIVILE,DIV ONCOL,SASSARI,ITALY. OSPED SAN MARTINO GENOVA,DIV HEMATOL,GENOA,ITALY. OSPED CIVILE,DIV HEMATOL,BOLZANO,ITALY. NATL CANC INST,GENOA,ITALY. OSPED CIVILE,DIV HEMATOL,CREMONA,ITALY. OSPED CIVILE,DIV ONCOL,NOALE,ITALY. INST HEMATOL,PARMA,ITALY. NR 21 TC 8 Z9 9 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUN PY 1991 VL 5 SU 1 BP 42 EP 45 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA GH798 UT WOS:A1991GH79800010 PM 1890865 ER PT J AU CHISESI, T SANTINI, G CAPNIST, G COSER, P CONTU, A PORCELLINI, A RIZZOLI, V SERTOLI, M RANCAN, L SALVAGNO, L VINANTE, O TEDESCHI, L AF CHISESI, T SANTINI, G CAPNIST, G COSER, P CONTU, A PORCELLINI, A RIZZOLI, V SERTOLI, M RANCAN, L SALVAGNO, L VINANTE, O TEDESCHI, L TI PROMACE-MOPP VS MACOP-B IN HIGH-GRADE NON-HODGKINS-LYMPHOMAS - A RANDOMIZED STUDY IN A MULTICENTER COOPERATIVE STUDY-GROUP (NHLCSG) SO LEUKEMIA LA English DT Article; Proceedings Paper CT 2ND VICENZA INTERNATIONAL WORKSHOP OF HEMATOLOGY : NEW INSIGHTS IN LYMPHOMAS CY MAY 29-31, 1991 CL VICENZE, ITALY SP ITALIAN SOC HEMATOL ID LARGE-CELL LYMPHOMA; COMBINATION CHEMOTHERAPY REGIMEN; BONE-MARROW TRANSPLANTATION; M-BACOD; CLINICAL-TRIALS; UNFAVORABLE HISTOLOGY; POOR-PROGNOSIS; SURVIVAL; THERAPY; UPDATE AB From January '85 to April '87, 81 patients (pts) with diffuse intermediate and high-grade non-Hodgkin's lymphomas were treated with the ProMace/MOPP protocol in a large Italian Cooperative Study Group (NHLCSG). Criteria for entry into the study included: no prior therapy, stage III-IV or stage II with bulky disease and/or B-symptoms, age below 65. 79 pts were evaluable for response. Almost all pts received six courses of chemotherapy, plus radiotherapy on bulky disease. 53 pts (67%) achieved complete remission (CR), 7 (9%) partial remission (PR), 4 (5%) were considered stable disease (SD) and 15 (19%) progression disease (PD) with 5 of them died early during treatment. The actuarial overall survival (OS) and disease free survival (DFS) are respectively 54% at 61 mos and 62% at 41 mos. The median follow-up from the end of therapy is 56 mos (range 40-68). Until now 20 pts (38%) relapsed on a median time of 8 mos (range 2-21) from CR. These data allowed to us to consider this regimen as effective as the third generation protocols also taking into account the multicenter basis of this study. With the aim to evaluate the impact of the third generation regimen on the outcome of these pts, a randomized study has been performed comparing ProMACE-MOPP with the third generation regimens MACOP-B. Therefore, from 1988 up to now, 206 pts with similar clinical and histological characteristics, have been enrolled in the two arms. No differences in terms of CR and DFS have been registered between the two treatments, with roughly the same toxicity. An analysis of prognostic factors in the larger series of pts treated with ProMACE-MOPP in the first and in the second study (167 pts) was performed. On these basis it seems reasonable that our next step would be to candidate these poor prognosis pts to a new therapeutic strategy which included the use of ABMT and/or PBSC transplantation as first line. C1 DEPT HEMATOL,VICENZA,ITALY. DIV HEMATOL,GENOA,ITALY. DIV HEMATOL,BOLZANO,ITALY. DIV ONCOL,SASSARI,ITALY. DIV HEMATOL,CREMONA,ITALY. INST HEMATOL,PARMA,ITALY. NATL CANC INST,GENOA,ITALY. INST ONCOL,PADUA,ITALY. DIV ONCOL,NOALE,ITALY. DIV MED ONCOL,MILAN,ITALY. NR 36 TC 8 Z9 8 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUN PY 1991 VL 5 SU 1 BP 107 EP 111 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA GH798 UT WOS:A1991GH79800024 PM 1716334 ER PT J AU LEBIHAN, D AF LEBIHAN, D TI FUTURE-DIRECTIONS IN MRI OF DIFFUSION AND MICROCIRCULATION SO MAGNETIC RESONANCE IN MEDICINE LA English DT Editorial Material RP LEBIHAN, D (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD JUN PY 1991 VL 19 IS 2 BP 209 EP 209 DI 10.1002/mrm.1910190202 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA FQ243 UT WOS:A1991FQ24300001 ER PT J AU LEBIHAN, D TURNER, R AF LEBIHAN, D TURNER, R TI INTRAVOXEL INCOHERENT MOTION IMAGING USING SPIN ECHOES SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article; Proceedings Paper CT MEETING/WORKSHOP ON FUTURE DIRECTIONS IN MRI OF DIFFUSION AND MICROCIRCULATION CY JUN 07-08, 1990 CL BETHESDA, MD SP SOC MAGNET RESONANCE MED, BERLEX, BRUKER, GE, MED SYST, PICKER INT, SALUTAR, SQUIBB DIAGNOST, TOSHIBA INT ID DIFFUSION-COEFFICIENTS; PERFUSION C1 NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RP LEBIHAN, D (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892, USA. RI Turner, Robert/C-1820-2008 NR 18 TC 41 Z9 41 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD JUN PY 1991 VL 19 IS 2 BP 221 EP 227 DI 10.1002/mrm.1910190206 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA FQ243 UT WOS:A1991FQ24300005 PM 1881307 ER PT J AU TURNER, R LEBIHAN, D CHESNICK, AS AF TURNER, R LEBIHAN, D CHESNICK, AS TI ECHO-PLANAR IMAGING OF DIFFUSION AND PERFUSION SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article; Proceedings Paper CT MEETING/WORKSHOP ON FUTURE DIRECTIONS IN MRI OF DIFFUSION AND MICROCIRCULATION CY JUN 07-08, 1990 CL BETHESDA, MD SP SOC MAGNET RESONANCE MED, BERLEX, BRUKER, GE, MED SYST, PICKER INT, SALUTAR, SQUIBB DIAGNOST, TOSHIBA INT ID INTRAVOXEL INCOHERENT MOTION C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NHLBI,BETHESDA,MD 20892. RP TURNER, R (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892, USA. RI Turner, Robert/C-1820-2008 NR 22 TC 89 Z9 93 U1 1 U2 10 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD JUN PY 1991 VL 19 IS 2 BP 247 EP 253 DI 10.1002/mrm.1910190210 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA FQ243 UT WOS:A1991FQ24300009 PM 1881311 ER PT J AU MOONEN, CTW PEKAR, J DEVLEESCHOUWER, MHM VANGELDEREN, P VANZIJL, PCM DESPRES, D AF MOONEN, CTW PEKAR, J DEVLEESCHOUWER, MHM VANGELDEREN, P VANZIJL, PCM DESPRES, D TI RESTRICTED AND ANISOTROPIC DISPLACEMENT OF WATER IN HEALTHY CAT BRAIN AND IN STROKE STUDIED BY NMR DIFFUSION IMAGING SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article; Proceedings Paper CT MEETING/WORKSHOP ON FUTURE DIRECTIONS IN MRI OF DIFFUSION AND MICROCIRCULATION CY JUN 07-08, 1990 CL BETHESDA, MD SP SOC MAGNET RESONANCE MED, BERLEX, BRUKER, GE, MED SYST, PICKER INT, SALUTAR, SQUIBB DIAGNOST, TOSHIBA INT ID MR C1 DELFT UNIV TECHNOL,DEPT APPL PHYS,DELFT,NETHERLANDS. GEORGETOWN UNIV,SCH MED,DEPT PHARMACOL,ROCKVILLE,MD 20850. RP MOONEN, CTW (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892, USA. RI van Zijl, Peter/B-8680-2008; Moonen, Chrit/K-4434-2016 OI Moonen, Chrit/0000-0001-5593-3121 NR 14 TC 94 Z9 95 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD JUN PY 1991 VL 19 IS 2 BP 327 EP 332 DI 10.1002/mrm.1910190223 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA FQ243 UT WOS:A1991FQ24300022 PM 1881322 ER PT J AU DELANNOY, J CHEN, CN TURNER, R LEVIN, RL LEBIHAN, D AF DELANNOY, J CHEN, CN TURNER, R LEVIN, RL LEBIHAN, D TI NONINVASIVE TEMPERATURE IMAGING USING DIFFUSION MRI SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article; Proceedings Paper CT MEETING/WORKSHOP ON FUTURE DIRECTIONS IN MRI OF DIFFUSION AND MICROCIRCULATION CY JUN 07-08, 1990 CL BETHESDA, MD SP SOC MAGNET RESONANCE MED, BERLEX, BRUKER, GE, MED SYST, PICKER INT, SALUTAR, SQUIBB DIAGNOST, TOSHIBA INT ID INTRAVOXEL INCOHERENT MOTION; NUCLEAR MAGNETIC-RESONANCE; HYPERTHERMIA; PERFUSION C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NIH,DIV RES SERV,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NIH,RADIAT ONCOL BRANCH,COP,DCT,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. RI Turner, Robert/C-1820-2008 NR 15 TC 71 Z9 73 U1 0 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD JUN PY 1991 VL 19 IS 2 BP 333 EP 339 DI 10.1002/mrm.1910190224 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA FQ243 UT WOS:A1991FQ24300023 PM 1881323 ER PT J AU GRALNICK, HR WILLIAMS, SB MCKEOWN, LP MAGRUDER, L HANSMANN, K VAIL, M PARKER, RI AF GRALNICK, HR WILLIAMS, SB MCKEOWN, LP MAGRUDER, L HANSMANN, K VAIL, M PARKER, RI TI PLATELET VONWILLEBRAND-FACTOR SO MAYO CLINIC PROCEEDINGS LA English DT Article ID VIII-RELATED ANTIGEN; VON WILLEBRAND FACTOR; BLEEDING-TIME; STIMULATED PLATELETS; MULTIMERIC STRUCTURE; BLOOD-PLATELETS; DISEASE; PLASMA; THROMBIN; COLLAGEN AB Von Willebrand factor (vWF) circulates in the blood in two distinct compartments. One, plasma vWF, is synthesized and released from endothelial cells; the second, synthesized by megakaryocytes, circulates in platelets primarily stored in the alpha-granules. Recent experimental and clinical studies of von Willebrand's disease (vWD) indicate that platelet vWF plays an important role in the bleeding time determination and the degree of clinical bleeding in vWD. Platelet vWF is released from the platelet alpha-granules by various agonists and then rebinds to the glycoprotein IIb/IIIa complex. Fibrinogen or monoclonal antibodies against this complex inhibit 60 to 70% of the expression of platelet vWF. Aspirin inhibits 80% of the adenosine diphosphate-induced platelet vWF surface expression, and the platelet vWF surface expression that is not inhibited by aspirin can be almost totally inhibited by disruption of the platelet cytoskeleton. Platelet vWF may, in part, be expressed in the open canalicular system prebound to a receptor. Transfusion studies have shown that correction of the bleeding time in severe vWD requires both plasma and platelet vWF. On the basis of numerous studies, we hypothesize that platelet vWF plays an important role in platelet interaction with the subendothelial surfaces under conditions of high shear stress. After platelet contact, platelet vWF is released, binds to the glycoprotein IIb/IIIa complex, and forms a bridge between the subendothelial surface and the platelet, which initiates and supports platelet spreading. Platelet vWF also acts as an intercellular bridge between platelets and thereby promotes platelet aggregation. This process is important not only in the initial steps of hemostasis but also in the process of thrombosis. RP GRALNICK, HR (reprint author), NIH,CTR CLIN,HEMATOL SERV,BETHESDA,MD 20892, USA. NR 37 TC 22 Z9 23 U1 0 U2 0 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JUN PY 1991 VL 66 IS 6 BP 634 EP 640 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA FR878 UT WOS:A1991FR87800011 PM 2046403 ER PT J AU LANGE, WR SCHWAN, TG FRAME, JD AF LANGE, WR SCHWAN, TG FRAME, JD TI CAN PROTRACTED RELAPSING FEVER RESEMBLE LYME-DISEASE SO MEDICAL HYPOTHESES LA English DT Article ID DIAGNOSIS AB We report the case of a Protestant missionary who contracted tick-borne relapsing fever in 1979 while serving in the Sudan. Despite tetracycline treatment, his acute illness ran a protracted course, with migratory polyarthralgias lasting approximately 10 months. Symptoms recurred in 1984 and have persisted. At regular intervals, the patient has experienced recurrent episodes of fever, generalized fatigue, bilateral upper and lower extremity muscle weakness, and asymetric large joint polyarthralgia. Indirect fluorescent antibody testing of sera demonstrated titers of 1:16 for B. burgdorferi and 1:64 for B. hermsii, and immunoblotting confirmed past exposure to relapsing fever, but not Lyme disease. It is hypothesized that this individual's chronic symptoms have been related to relapsing fever, and that in certain situations or in selected individuals, relapsing fever can be capable of producing a chronic clinical picture analogous to Lyme disease. C1 JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NIAID,ROCKY MT LABS,PATHOBIOL LAB,HAMILTON,MT 59840. COLUMBIA UNIV COLL PHYS & SURG,DIV TROP MED,NEW YORK,NY 10032. NR 16 TC 10 Z9 10 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD JUN PY 1991 VL 35 IS 2 BP 77 EP 79 DI 10.1016/0306-9877(91)90026-U PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA FT512 UT WOS:A1991FT51200003 PM 1890979 ER PT J AU ALI, PO SIMPSON, AJG ALLEN, R WATERS, AP HUMPHRIES, CJ JOHNSTON, DA ROLLINSON, D AF ALI, PO SIMPSON, AJG ALLEN, R WATERS, AP HUMPHRIES, CJ JOHNSTON, DA ROLLINSON, D TI SEQUENCE OF A SMALL SUBUNIT RIBOSOMAL-RNA GENE OF SCHISTOSOMA-MANSONI AND ITS USE IN PHYLOGENETIC ANALYSIS SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE SCHISTOSOMA-MANSONI; SMALL SUBUNIT RIBOSOMAL-RNA; PHYLOGENY; 18S RIBOSOMAL-RNA ID RIBOSOMAL-RNA GENES; IDENTIFICATION; COMPILATION; DNA AB The complete sequence of a small ribosomal RNA gene of Schistosoma mansoni contained within plasmids pSM389 and pSM889 is presented. It was found to be 1992 bp in length, larger than that of most eukaryotes. Extra nucleotides occur in regions known to be variable (V4 and V7). The predicted secondary structure of the nucleotides 660-853 revealed additional helices which have been designated E21-1A and E21-1B. The other region to differ from higher eukaryotes lies between nucleotides 1457 and 1569. Secondary structure prediction demonstrated that a single extended helix may be formed from this part of the schistosome small subunit rRNA sequence. Nucleotides that could be unambiguously aligned with those of 12 other eukaryotes were used to estimate phylogenetic relationships. The consensus tree obtained by Maximum Parsimony analysis showed the schistosome as a sister taxon to the flatworm Dugesia tigrina. C1 NAT HIST MUSEUM, DEPT ZOOL, CROMWELL RD, LONDON SW7 5BD, ENGLAND. NATL INST MED RES, DIV PARASITOL, LONDON NW7 1AA, ENGLAND. NIAID, PARASIT DIS LAB, MALARIA SECT, BETHESDA, MD 20892 USA. RI Waters, Andy/C-9377-2009; Rollinson, David/C-7406-2009 OI Waters, Andy/0000-0001-8900-2982; FU Wellcome Trust NR 22 TC 36 Z9 37 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD JUN PY 1991 VL 46 IS 2 BP 201 EP 208 DI 10.1016/0166-6851(91)90044-7 PG 8 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA FM833 UT WOS:A1991FM83300002 PM 1922195 ER PT J AU MOELANS, IIMD KLAASSEN, CHW KASLOW, DC KONINGS, RNH SCHOENMAKERS, JGG AF MOELANS, IIMD KLAASSEN, CHW KASLOW, DC KONINGS, RNH SCHOENMAKERS, JGG TI MINIMAL VARIATION IN PFS16, A NOVEL PROTEIN LOCATED IN THE MEMBRANE OF GAMETES AND SPOROZOITES OF PLASMODIUM-FALCIPARUM SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Note DE PLASMODIUM-FALCIPARUM; MALARIA; VACCINE CANDIDATE ID SEXUAL STAGE C1 CATHOLIC UNIV NIJMEGEN,FAC SCI,DEPT MOLEC BIOL,6525 ED NIJMEGEN,NETHERLANDS. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. NR 11 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD JUN PY 1991 VL 46 IS 2 BP 311 EP 313 DI 10.1016/0166-6851(91)90056-C PG 3 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA FM833 UT WOS:A1991FM83300014 PM 1922202 ER PT J AU GOODWIN, RG ANDERSON, D JERZY, R DAVIS, T BRANNAN, CI COPELAND, NG JENKINS, NA SMITH, CA AF GOODWIN, RG ANDERSON, D JERZY, R DAVIS, T BRANNAN, CI COPELAND, NG JENKINS, NA SMITH, CA TI MOLECULAR-CLONING AND EXPRESSION OF THE TYPE-1 AND TYPE-2 MURINE RECEPTORS FOR TUMOR-NECROSIS-FACTOR SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN KINASE-C; MONOCLONAL-ANTIBODIES; CELL-SURFACE; SOLUBLE FORM; SEQUENCE; LOCALIZATION; HOMOLOGY; BINDING; IDENTIFICATION; PURIFICATION AB Clones encoding the type 1 (p80) and type 2 (p60) forms of the murine receptors for tumor necrosis factor (TNF) were isolated by cross-hybridization using probes derived from the cloned human TNF receptors. Each of the murine receptors shows strong sequence homology to the corresponding human receptor (approximately 65% amino acid identity) throughout the molecule but only modest homology, limited to ligand-binding domains, between themselves. The ligand-binding characteristics of the recombinant murine receptors mirror those of the human homologs: both receptor types bind TNF-alpha and -beta with multiple affinity classes, and the ligands cross-compete. Analysis of the murine transcripts encoding these receptors revealed the presence of RNAs for one or both forms of the receptors in all cells examined. It was also demonstrated that for both types of human TNF receptor, variably sized transcripts are observed in different cells. The murine cDNAs were further used to determine the chromosomal locations of the TNF receptor genes. They are not linked, in contrast to the ligands, and map to chromosomes 4 (type 1) and 6 (type 2). C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RP GOODWIN, RG (reprint author), IMMUNEX CORP,51 UNIV ST,SEATTLE,WA 98101, USA. FU NCI NIH HHS [N01-CO-74101] NR 36 TC 178 Z9 180 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1991 VL 11 IS 6 BP 3020 EP 3026 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FM852 UT WOS:A1991FM85200012 PM 1645445 ER PT J AU RAMIREZ, M WEK, RC HINNEBUSCH, AG AF RAMIREZ, M WEK, RC HINNEBUSCH, AG TI RIBOSOME ASSOCIATION OF GCN2 PROTEIN-KINASE, A TRANSLATIONAL ACTIVATOR OF THE GCN4 GENE OF SACCHAROMYCES-CEREVISIAE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSFER RNA-SYNTHETASES; AMINO-ACID AVAILABILITY; INITIATION FACTOR-II; DOUBLE-STRANDED-RNA; MESSENGER-RNA; YEAST; EXPRESSION; SUBUNIT; PHOSPHORYLATION; DISSOCIATION AB The GCN4 gene of the yeast Saccharomyces cerevisiae encodes a transcriptional activator of amino acid biosynthetic genes that is regulated at the translational level according to the availability of amino acids. GCN2 is a protein kinase required for increased translation of GCN4 mRNA in amino acid-starved cells. Centrifugation of cell extracts in sucrose gradients indicated that GCN2 comigrates with ribosomal subunits and polysomes. The fraction of GCN2 cosedimenting with polysomes was reduced under conditions in which polysomes were dissociated, suggesting that GCN2 is physically bound to these structures. When the association of 40S and 60S subunits was prevented by omitting Mg2+ from the gradient, almost all of the GCN2 comigrated with 60S ribosomal subunits, and it remained bound to these particles during gel electrophoresis under nondenaturing conditions. GCN2 could be dissociated from 60S subunits by 0.5 M KCl, suggesting that it is loosely associated with ribosomes rather than being an integral ribosomal protein. Accumulation of GCN2 on free 43S-48S particles and 60S subunits occurred during polysome runoff in vitro and under conditions of reduced growth rate in vivo. These observations, plus the fact that GCN2 shows preferential association with free ribosomal subunits during exponential growth, suggest that GCN2 interacts with ribosomes during the translation initiation cycle. The extreme carboxyl-terminal segment of GCN2 is essential for its interaction with ribosomes. These sequences are also required for the ability of GCN2 to stimulate GCN4 translation in vivo, leading us to propose that ribosome association by GCN2 is important for its access to substrates in the translational machinery or for the detecting uncharged tRNA in amino acid-starved cells. C1 NICHHD,MOLEC GENET LAB,MOLEC GENET LOWER EUKARYOTES SECT,BETHESDA,MD 20892. NR 35 TC 104 Z9 105 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1991 VL 11 IS 6 BP 3027 EP 3036 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FM852 UT WOS:A1991FM85200013 PM 2038314 ER PT J AU BEECHAM, EJ MUSHINSKI, JF SHACTER, E POTTER, M BOHR, VA AF BEECHAM, EJ MUSHINSKI, JF SHACTER, E POTTER, M BOHR, VA TI DNA-REPAIR IN THE C-MYC PROTOONCOGENE LOCUS - POSSIBLE INVOLVEMENT IN SUSCEPTIBILITY OR RESISTANCE TO PLASMACYTOMA INDUCTION IN BALB/C MICE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DIHYDROFOLATE-REDUCTASE GENE; HAMSTER OVARY CELLS; DIFFERENTIAL REPAIR; DHFR GENE; TRANSCRIPTION; DAMAGE; INCREASES; REMOVAL; REGION; FAMILY AB This report describes an unexpected difference in the efficiency of removal of UV-induced DNA damage in the c-myc locus in splenic B lymphoblasts from two inbred strains of mice. In cells from plasmacytoma-resistant DBA/2N mice, 35% of UV-induced damage in the regulatory and 5' flank of c-myc is removed by 12 h. However, in cells from plasmacytoma-susceptible BALB/cAn mice, damage is not removed from this region. In the protein-encoding region and 3' flank of c-myc as well as in two dihydrofolate reductase gene fragments, UV damage is repaired with similar efficiency in B lymphoblasts from both strains of mice. Furthermore, in the protein-encoding portion and 3' flank of c-myc, damage is selectively removed from only the transcribed strand. No repair is detected in the nontranscribed strand. In contrast, DNA repair in the 5' flank of c-myc is not strand specific; in DNA from DBA/2N cells, UV damage is rapidly removed from both the transcribed and nontranscribed strands. In BALB/cAn cells no repair was detected in either strand in the 5' flank, consistent with the results with double-stranded, nick-translated probes to this region of c-myc. In addition to the repair studies, we have detected post-UV-damage formation: in most of the genes studied, we find that additional T4 endonuclease-sensitive sites are formed in the DNA 2 h after irradiation. Our findings provide new insights into the details of gene-specific and strand-specific DNA repair and suggest that there may be close links between DNA repair and B-cell neoplastic development. C1 NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NCI,GENET LAB,BETHESDA,MD 20892. NR 32 TC 48 Z9 48 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1991 VL 11 IS 6 BP 3095 EP 3104 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FM852 UT WOS:A1991FM85200021 PM 1710024 ER PT J AU DECLUE, JE STONE, JC BLANCHARD, RA PAPAGEORGE, AG MARTIN, P ZHANG, K LOWY, DR AF DECLUE, JE STONE, JC BLANCHARD, RA PAPAGEORGE, AG MARTIN, P ZHANG, K LOWY, DR TI A RAS EFFECTOR DOMAIN MUTANT WHICH IS TEMPERATURE SENSITIVE FOR CELLULAR-TRANSFORMATION - INTERACTIONS WITH GTPASE-ACTIVATING PROTEIN AND NF-1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MURINE SARCOMA-VIRUS; GENE-PRODUCT; ENCODED P21; GAP; IDENTIFICATION; CONSTRUCTION; MUTAGENESIS; SEQUENCES; RAS-P21; FAMILY AB A series of v-ras(H) effector domain mutants were analyzed for their ability to transform rat 2 cells at either low or high temperatures. Three mutants were found to be significantly temperature sensitive: Ile-36 changed to Leu, Ser-39 changed to Cys (S39C), and Arg-41 changed to Leu. Of these, the codon 39 mutant (S39C) showed the greatest degree of temperature sensitivity. When the same mutation was analyzed in the proto-oncogene form of ras (c-ras(H)), this gene was also found to be temperature sensitive for transformation. Biochemical analysis of the proteins encoded by v-ras(H)(S39C) and c-ras(H)(S39C) demonstrated that the encoded p21ras proteins were stable and bound guanine nucleotides in vivo at permissive and nonpermissive temperatures. On the basis of these findings, it is likely that the temperature-sensitive phenotype results from an inability of the mutant (S39C) p21ras to interact properly with the ras target effector molecule(s) at the nonpermissive temperature. We therefore analyzed the interaction between the c-ras(H)(S39C) protein and the potential target molecules GTPase-activating protein (GAP) and the GAP-related domain of NF-1, on the basis of stimulation of the mutant p21ras GTPase activity by these molecules in vitro. Assays conducted across a range of temperatures revealed no temperature sensitivity for stimulation of the mutant protein, compared with that of authentic c-ras(H) protein. We conclude that for this mutant, there is a dissociation between the stimulation of p21ras GTPase activity by GAP and the GAP-related domain NF-1 and their potential target function. Our results are also consistent with the existence of a distinct, as-yet-unidentified effector for mammalian ras proteins. C1 NCI,CELLULAR ONCOL LAB,BLDG 37,ROOM 1B-26,BETHESDA,MD 20892. UNIV ALBERTA,DEPT BIOCHEM,EDMONTON T6G 2H7,ALBERTA,CANADA. NR 37 TC 34 Z9 34 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1991 VL 11 IS 6 BP 3132 EP 3138 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FM852 UT WOS:A1991FM85200025 PM 2038322 ER PT J AU SEGATTO, O LONARDO, F WEXLER, D FAZIOLI, F PIERCE, JH BOTTARO, DP WHITE, MF DIFIORE, PP AF SEGATTO, O LONARDO, F WEXLER, D FAZIOLI, F PIERCE, JH BOTTARO, DP WHITE, MF DIFIORE, PP TI THE JUXTAMEMBRANE REGIONS OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR AND GP185ERBB-2 DETERMINE THE SPECIFICITY OF SIGNAL TRANSDUCTION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID STIMULATES TYROSINE PHOSPHORYLATION; PHOSPHOLIPASE-C-GAMMA; PDGF BETA-RECEPTOR; PROTEIN KINASE-C; EGF RECEPTOR; MITOGENIC RESPONSE; INSULIN-RECEPTOR; 3T3 CELLS; THREONINE; ERBB-2 AB The epidermal growth factor receptor (EGFR) and gp185erbB-2 are closely related tyrosine kinases. Despite extensive sequence and structural homology, these two receptors display quantitative and qualitative differences in their ability to couple with mitogenic signalling pathways. By using chimeric molecules between EGFR and erbB-2, we found that the determinants responsible for the specificity of mitogenic signal transduction are located in the amino-terminal half of the tyrosine kinase domain of either receptor. In the EGFR, mutational analysis within this subdomain revealed that deletion of residues 660 to 667 impaired receptor mitogenic activity without affecting its tyrosine kinase properties. This sequence is therefore likely to contribute to the specificity of substrate recognition by the EGFR kinase. C1 NCI,MOLEC & CELLULAR BIOL LAB,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02115. RI Bottaro, Donald/F-8550-2010; Di Fiore, Pier Paolo/K-2130-2012 OI Bottaro, Donald/0000-0002-5057-5334; Di Fiore, Pier Paolo/0000-0002-2252-0950 FU NIDDK NIH HHS [DK38712] NR 46 TC 51 Z9 51 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1991 VL 11 IS 6 BP 3191 EP 3202 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FM852 UT WOS:A1991FM85200032 PM 1674818 ER PT J AU FOIANI, M CIGAN, AM PADDON, CJ HARASHIMA, S HINNEBUSCH, AG AF FOIANI, M CIGAN, AM PADDON, CJ HARASHIMA, S HINNEBUSCH, AG TI GCD2, A TRANSLATIONAL REPRESSOR OF THE GCN4 GENE, HAS A GENERAL FUNCTION IN THE INITIATION OF PROTEIN-SYNTHESIS IN SACCHAROMYCES-CEREVISIAE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID POLYPEPTIDE-CHAIN INITIATION; RABBIT RETICULOCYTE LYSATE; AMINO-ACID BIOSYNTHESIS; 60S RIBOSOMAL-SUBUNITS; MESSENGER-RNA; CELL-CYCLE; YEAST; PHOSPHORYLATION; INHIBITION; COMPLEXES AB The GCD2 protein is a translational repressor of GCN4, the transcriptional activator of multiple amino acid biosynthetic genes in Saccharomyces cerevisiae. We present evidence that GCD2 has a general function in the initiation of protein synthesis in addition to its gene-specific role in translational control of GCN4 expression. Two temperature-sensitive lethal gcd2 mutations result in sensitivity to inhibitors of protein synthesis at the permissive temperature, and the gcd2-503 mutation leads to reduced incorporation of labeled leucine into total protein following a shift to the restrictive temperature of 36-degrees-C. The gcd2-503 mutation also results in polysome runoff, accumulation of inactive 80S ribosomal couples, and accumulation of at least one of the subunits of the general translation initiation factor 2 (eIF-2-alpha) in 43S-48S particles following a shift to the restrictive temperature. The gcd2-502 mutation causes accumulation of 40S subunits in polysomes, known as halfmers, that are indicative of reduced 40S-60S subunit joining at the initiation codon. These phenotypes suggest that GCD2 functions in the translation initiation pathway at a step following the binding of eIF-2 . GTP . Met-tRNA(i)Met to 40S ribosomal subunits. Consistent with this hypothesis, we found that inhibiting 40S-60S subunit joining by deleting one copy (RPL16B) of the duplicated gene encoding the 60S ribosomal protein L16 qualitatively mimics the phenotype of gcd2 mutations in causing derepression of GCN4 expression under nonstarvation conditions. However, deletion of RPL16B also prevents efficient derepression of GCN4 under starvation conditions, indicating that lowering the concentration of 60S subunits and reducing GCD2 function affect translation initiation at GCN4 in different ways. This distinction is in accord with a recently proposed model for GCN4 translational control in which ribosomal reinitiation at short upstream open reading frames in the leader of GCN4 mRNA is suppressed under amino acid starvation conditions to allow for increased reinitiation at the GCN4 start codon. C1 NICHHD,MOLEC GENET LOWER EUKARYOTES SECT,BETHESDA,MD 20892. RI Foiani, Marco/M-8234-2014 OI Foiani, Marco/0000-0003-4795-834X NR 56 TC 141 Z9 142 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1991 VL 11 IS 6 BP 3203 EP 3216 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FM852 UT WOS:A1991FM85200033 PM 2038326 ER PT J AU CIGAN, AM FOIANI, M HANNIG, EM HINNEBUSCH, AG AF CIGAN, AM FOIANI, M HANNIG, EM HINNEBUSCH, AG TI COMPLEX-FORMATION BY POSITIVE AND NEGATIVE TRANSLATIONAL REGULATORS OF GCN4 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INITIATION FACTOR-II; AMINO-ACID BIOSYNTHESIS; POLYPEPTIDE-CHAIN INITIATION; RABBIT RETICULOCYTE LYSATE; NUCLEOTIDE-EXCHANGE FACTOR; SACCHAROMYCES-CEREVISIAE; PROTEIN-SYNTHESIS; MESSENGER-RNA; REVERSING FACTOR; ALPHA-SUBUNIT AB GCN4 is a transcriptional activator of amino acid biosynthetic genes in Saccharomyces cerevisiae whose expression is regulated by amino acid availability at the translational level. GCD1 and GCD2 are negative regulators required for the repression of GCN4 translation under nonstarvation conditions that is mediated by upstream open reading frames (uORFs) in the leader of GCN4 mRNA. GCD factors are thought to be antagonized by the positive regulators GCN1, GCN2, and GCN3 in amino acid-starved cells to allow for increased GCN4 protein synthesis. Previous genetic studies suggested that GCD1, GCD2, and GCN3 have closely related functions in the regulation of GCN4 expression that involve translation initiation factor 2 (eIF-2). In agreement with these predictions, we show that GCD1, GCD2, and GCN3 are integral components of a high-molecular-weight complex of approximately 600,000 Da. The three proteins copurified through several biochemical fractionation steps and could be coimmunoprecipitated by using antibodies against GCD1 or GCD2. Interestingly, a portion of the eIF-2 present in cell extracts also cofractionated and coimmunoprecipitated with these regulatory proteins but was dissociated from the GCD1/GCD2/GCN3 complex by 0.5 M KCl. Incubation of a temperature-sensitive gcd1-101 mutant at the restrictive temperature led to a rapid reduction in the average size and quantity of polysomes, plus an accumulation of inactive 80S ribosomal couples; in addition, excess amounts of eIF-2-alpha, GCD1, GCD2, and GCN3 were found comigrating with free 40S ribosomal subunits. These results suggest that GCD1 is required for an essential function involving eIF-2 at a late step in the translation initiation cycle. We propose that lowering the function of this high-molecular-weight complex, or of eIF-2 itself, in amino acid-starved cells leads to reduced ribosomal recognition of the uORFs and increased translation initiation at the GCN4 start codon. Our results provide new insights into how general initiation factors can be regulated to affect gene-specific translational control. C1 NICHHD,MOLEC GENET LAB,MOLEC GENET LOWER EUKARYOTES SECT,BETHESDA,MD 20892. RI Foiani, Marco/M-8234-2014 OI Foiani, Marco/0000-0003-4795-834X NR 56 TC 103 Z9 103 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1991 VL 11 IS 6 BP 3217 EP 3228 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FM852 UT WOS:A1991FM85200034 PM 2038327 ER PT J AU ADAM, RD NASH, TE WELLEMS, TE AF ADAM, RD NASH, TE WELLEMS, TE TI TELOMERIC LOCATION OF GIARDIA RDNA GENES SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID UNUSUAL RIBOSOMAL-RNA; FALCIPARUM CHROMOSOMES; PLASMODIUM-FALCIPARUM; GEL-ELECTROPHORESIS; RICH PROTEIN; DNA-SEQUENCE; LAMBLIA; IDENTIFICATION; SEPARATION; REPEAT AB Giardia lamblia telomeres have been isolated from a library enriched for repaired chromosome ends by (i) screening with a Plasmodium falciparum telomere and (ii) differential hybridization with Bal 31-digested and total G. lamblia DNA. Analysis of three clones isolated by this strategy has identified multiple tandem repeats of the 5-mer TAGGG. An oligonucleotide containing these repeats recognizes Bal 31-sensitive bands in Southern hybridizations and detects all G. lamblia chromosomes in pulsed-field gel electrophoresis separations. An abrupt transition from the G. lamblia rDNA sequence to telomeric repeats has been found in all three clones. In two of the clones the transition occurs at the same site, near the beginning of the large subunit rDNA sequence. In the third clone the transition occurs at a site in the intergenic spacer sequence between the rDNA genes. Hybridization of an rDNA probe to a pulsed-field separation of G. lamblia chromosomes indicates that rDNA genes are present on several chromosomes but vary in location from isolate to isolate. These results suggest that rRNA genes are clustered at telomeric locations in G. lamblia and that these clusters are mobile. C1 UNIV ARIZONA,DEPT MICROBIOL IMMUNOL,TUCSON,AZ 85724. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. RP ADAM, RD (reprint author), UNIV ARIZONA,DEPT INTERNAL MED,INFECT DIS SECT,TUCSON,AZ 85724, USA. NR 30 TC 61 Z9 63 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1991 VL 11 IS 6 BP 3326 EP 3330 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FM852 UT WOS:A1991FM85200045 PM 2038335 ER PT J AU SETHUMADHAVAN, K BELLINO, FL THOTAKURA, NR AF SETHUMADHAVAN, K BELLINO, FL THOTAKURA, NR TI ESTROGEN SYNTHETASE (AROMATASE) - THE CYTOCHROME-P-450 COMPONENT OF THE HUMAN PLACENTAL ENZYME IS A GLYCOPROTEIN SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE ESTROGEN SYNTHETASE; AROMATASE; CYTOCHROME-P-450; NADPH CYTOCHROME-P-450 REDUCTASE; GLYCOPROTEIN; RECONSTITUTION ACTIVITY; (HUMAN PLACENTA) ID N-ACETYLGLUCOSAMINIDASE-F; ENCODING HUMAN AROMATASE; MICROSOMAL CYTOCHROME-P-450; GLYCOSIDASE-F; C REDUCTASE; PURIFICATION; SYSTEM; DEGLYCOSYLATION; CHROMATOGRAPHY; ANTIBODY AB Estrogen synthetase (aromatase) is a cytochrome P-450 enzyme system which converts androgens to estrogens. Although this enzyme has been purified and the cDNA-derived amino acid sequence elucidated, very little is known regarding post-translational modifications of this physiologically crucial enzyme. We show here that the cytochrome P-450 component, P-450ES, purified from human term placental microsomes, is a glycoprotein based on the following evidence: its molecular weight is decreased following treatment with endoglycosidase F, concanavalin A-biotin specifically binds to this protein immobilized on nitrocellulose, and its oligosaccharide composition is consistent with a single N-linked fucosylated complex type carbohydrate chain. In a reconstitution system, the aromatase activity using the endoglycosidase F-treated P-450ES was reduced by about 35-40% relative to the native form, regardless of whether androstenedione or testosterone was used as substrate. C1 SUNY BUFFALO,DEPT BIOL SCI,BUFFALO,NY 14260. NIDDKD,MOLEC CELLULAR & NUTR ENDOCRINOL BRANCH,BETHESDA,MD 20892. FU NICHD NIH HHS [HD16593] NR 37 TC 37 Z9 37 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JUN PY 1991 VL 78 IS 1-2 BP 25 EP 32 DI 10.1016/0303-7207(91)90182-R PG 8 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA FR119 UT WOS:A1991FR11900010 PM 1936523 ER PT J AU JANSEN, E STEENBERGH, PH LEROITH, D ROBERTS, CT SUSSENBACH, JS AF JANSEN, E STEENBERGH, PH LEROITH, D ROBERTS, CT SUSSENBACH, JS TI IDENTIFICATION OF MULTIPLE TRANSCRIPTION START SITES IN THE HUMAN INSULIN-LIKE GROWTH FACTOR-I GENE SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE INSULIN-LIKE GROWTH FACTOR-I; TRANSCRIPTION START SITES; LEADER EXON; POLYMERASE CHAIN REACTION; RNASE PROTECTION ID MESSENGER RIBONUCLEIC-ACID; 5' UNTRANSLATED REGION; SMOOTH-MUSCLE TUMORS; IGF-I; 5'-UNTRANSLATED REGIONS; NUCLEOTIDE-SEQUENCE; MOLECULAR-CLONING; RAT; RNA; TRANSLATION AB We have localized four transcription initiation sites in the human insulin-like growth factor-I (IGF-I) gene. Two transcription start sites were identified which result in a longer and shorter version of the leader derived from the known exon 1 of the IGF-I gene. Transcription starting at the upstream transcription initiation site results in a leader exon 1 of about 1155 nucleotides (nt), whereas transcription starting at the downstream initiation site results in a leader of about 240 nt. The majority of the transcripts initiate at the latter site. We further identified a region in the human IGF-I gene between exons 1 and 2, which shows a high degree of homology with the rat IGF-I leader exon 1B. By means of the polymerase chain reaction (PCR) we detected human IGF-I mRNAs containing this novel leader. The corresponding exon was designated exon IB according to the rat IGF-I gene terminology. PCR and RNase protection analyses identified two transcription start sites within this alternative leader exon IB. Transcription initiated at the most upstream start site results in a leader of about 750 nt, whereas transcription starting at the downstream site is heterogeneous, resulting in leaders of 65-75 nt long. No consensus TATA-box or AT-rich regions are present immediately upstream of all four transcription start sites identified, nor are these regions particularly GC-rich. The IGF-I gene is known to be expressed differentially in a tissue- and development-specific fashion. Differential activation of multiple promoters could very well play a crucial role in IGF-I gene regulation. C1 NIDDK,DIABET BRANCH,MOLEC & CELLULAR PHYSIOL,BETHESDA,MD. RP JANSEN, E (reprint author), STATE UNIV UTRECHT,PHYSIOL CHEM LAB,VONDELLAAN 24A,3521 GG UTRECHT,NETHERLANDS. OI Roberts, Charles/0000-0003-1756-5772 NR 30 TC 77 Z9 80 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JUN PY 1991 VL 78 IS 1-2 BP 115 EP 125 DI 10.1016/0303-7207(91)90192-U PG 11 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA FR119 UT WOS:A1991FR11900020 PM 1936520 ER PT J AU NOGUCHI, K KOWALSKI, K TRAUB, R SOLODKIN, A IADAROLA, MJ RUDA, MA AF NOGUCHI, K KOWALSKI, K TRAUB, R SOLODKIN, A IADAROLA, MJ RUDA, MA TI DYNORPHIN EXPRESSION AND FOS-LIKE IMMUNOREACTIVITY FOLLOWING INFLAMMATION INDUCED HYPERALGESIA ARE COLOCALIZED IN SPINAL-CORD NEURONS SO MOLECULAR BRAIN RESEARCH LA English DT Article DE INSITU HYBRIDIZATION HISTOCHEMISTRY; IMMUNOCYTOCHEMISTRY; DORSAL HORN; PAIN; NOCICEPTION; MESSENGER RNA; PROTOONCOGENE ID IMMEDIATE-EARLY GENES; DNA-BINDING ACTIVITY; C-FOS; OPIOID RECEPTOR; MESSENGER-RNAS; NERVOUS-SYSTEM; RAT; PROTEIN; STIMULATION; INDUCTION AB Fos and Fos-related proteins are increased in spinal dorsal horn neurons following noxious stimulation. The laminar location of neurons that exhibit this increase is coincident with those that exhibit an increase in dynorphin in a rat model of peripheral inflammation and hyperalgesia. In order to determine whether the increase in Fos or related proteins and dynorphin occurs in the same dorsal horn neurons, two kinds of double-labeling methods were used: in situ hybridization histochemistry to label dynorphin mRNA autoradiographically, and immunocytochemistry to label Fos and Fos-related proteins, or a double immunocytochemical method that labeled Fos and Fos-related proteins and dynorphin peptide with distinct chromogens. With both methods more than 80% of the neurons in laminae I, II, V and VI exhibiting an increase in either dynorphin mRNA or peptide following peripheral inflammation also colocalized increased nuclear Fos-like immunoreactivity. However, the number of neurons displaying increased Fos-like immunoreactivity was substantially greater than the number of neurons colocalizing increased dynorphin. These data suggest that the activation of nuclear Fos and Fos-related proteins may be related to the induction of dynorphin gene expression in a subpopulation of spinal cord neurons following peripheral inflammation and hyperalgesia. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BLDG 30,ROOM B-20,BETHESDA,MD 20892. OI Traub, Richard/0000-0001-8633-6311 NR 37 TC 198 Z9 199 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD JUN PY 1991 VL 10 IS 3 BP 227 EP 233 DI 10.1016/0169-328X(91)90065-6 PG 7 WC Neurosciences SC Neurosciences & Neurology GA FR990 UT WOS:A1991FR99000005 ER PT J AU AGOSTON, DV EIDEN, LE BRENNEMAN, DE GOZES, I AF AGOSTON, DV EIDEN, LE BRENNEMAN, DE GOZES, I TI SPONTANEOUS ELECTRICAL-ACTIVITY REGULATES VASOACTIVE-INTESTINAL-PEPTIDE EXPRESSION IN DISSOCIATED SPINAL-CORD CELL-CULTURES SO MOLECULAR BRAIN RESEARCH LA English DT Article DE VASOACTIVE INTESTINAL POLYPEPTIDE; PHENOTYPE; ELECTRICAL ACTIVITY; DEVELOPMENT; CENTRAL NERVOUS SYSTEM ID MESSENGER-RNA; SYMPATHETIC NEURONS; GENE-EXPRESSION; VIP-GENE; RAT; SEQUENCE; DEPOLARIZATION; ENKEPHALIN; SURVIVAL; BLOCKADE AB Activity-dependent expression of vasoactive intestinal peptide (VIP) was investigated in spinal cord/dorsal root ganglia cultures derived from embryonic mice. Since all spinal cord neurons appear to exhibit spontaneous action potentials after one week in vitro, activity-dependent regulation of VIP-transcripts (mRNA(VIP)) could be studied with or without electrical blockade induced by tetrodotoxin (TTX). In 10-day-old cultures, a 50% decrease in mRNA(VIP) was observed after 3 days of treatment with TTX. The decrease in mRNA(VIP) was reversed upon removal of the TTX and was dependent on the age of the cultures: no decreases from control were observed in 5-day-old cultures and much smaller decrements were produced in one month old cultures treated with TTX. A variety of neuroactive substances were tested for effects on mRNA(VIP) in electrically active and electrically blocked cultures. Application of 8-bromo-cAMP (cAMP), N-methyl-D-aspartate (NMDA), substance P, muscimol, A23187 and VIP to electrically active cultures resulted in a 2- to 3-fold increase in mRNA(VIP), while phorbol myristate 13-acetate (PMA) and 8-bromo-cGMP (cGMP) had no effect. In contrast, electrically inactive cultures exhibited a 3 to 4-fold increase in mRNA(VIP) after treatment with PMA, cAMP and VIP, while NMDA, substance P, muscimol, A23187 and cGMP produced no increases. In the regulation of VIP gene expression in embryonic spinal cord neurons shows a temporal sensitivity to TTX-induced electrical blockade and may be mediated by multiple neurotransmitter inputs which converge on cAMP- and calcium-related processes in an activity-dependent manner. C1 NICHHD,DEV NEUROBIOL LAB,NEUROCHEM UNIT,BLDG 36,ROOM 2A21,BETHESDA,MD 20892. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. TEL AVIV UNIV,SACKLER SCH MED,DEPT CHEM PATHOL,TEL AVIV,ISRAEL. OI Eiden, Lee/0000-0001-7524-944X NR 38 TC 42 Z9 43 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD JUN PY 1991 VL 10 IS 3 BP 235 EP 240 DI 10.1016/0169-328X(91)90066-7 PG 6 WC Neurosciences SC Neurosciences & Neurology GA FR990 UT WOS:A1991FR99000006 ER PT J AU BONEWALD, LF WAKEFIELD, L OREFFO, ROC ESCOBEDO, A TWARDZIK, DR MUNDY, GR AF BONEWALD, LF WAKEFIELD, L OREFFO, ROC ESCOBEDO, A TWARDZIK, DR MUNDY, GR TI LATENT FORMS OF TRANSFORMING GROWTH-FACTOR-BETA (TGF-BETA) DERIVED FROM BONE CULTURES - IDENTIFICATION OF A NATURALLY-OCCURRING 100-KDA COMPLEX WITH SIMILARITY TO RECOMBINANT LATENT TGF-BETA SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID MOLECULAR-WEIGHT COMPLEX; HAMSTER OVARY CELLS; OSTEO-SARCOMA CELLS; FACTOR-BETA-1 PRECURSOR; ALKALINE-PHOSPHATASE; ISOLATED OSTEOCLASTS; MANNOSE 6-PHOSPHATE; EMBRYO FIBROBLASTS; HUMAN-PLATELETS; EXPRESSION AB Transforming growth factor-beta (TGF-beta) is produced by most tissues, including bone, as a complex that is biologically inert. Release of TGF-beta homodimer from this latent complex is necessary for TGF-beta to exert effects on target cells. Thus, the nature of the latent complex and the mechanisms responsible for TGF-beta release are the key to understanding TGF-beta actions. We have found that murine calvarial bone cultures secrete multiple latent forms of TGF-beta. Using analytical chromatography and Western blot analysis, we have compared bone latent TGF-beta with the previously characterized latent complex present in platelets and with simian TGF-beta precursor, which is stably expressed in a latent form by Chinese hamster ovarian (CHO) cells. A major component of the bone material appears to be a latent complex of 100 kDa, consisting of mature TGF-beta (25-kDa homodimer) noncovalently associated with the remainder of the TGF-beta precursor proregion (75-kDa homodimer). Like the recombinant TGF-beta precursor, it elutes from a Mono-Q fast pressure liquid chromatography anion exchange column at 0.2 M NaCl and shows a very similar banding pattern on Western blots. Thus, this bone complex closely resembles recombinant TGF-beta precursor expressed in a latent form by CHO cells and differs from the naturally occurring platelet complex, which has an additional 135-kDa binding protein that is bound through disulfide bonds to the precursor proregion. Western blot analysis also indicates that, like CHO cells, which express recombinant TGF-beta precursor, but unlike other cell types, the bone cultures secrete detectable amounts of uncleaved TGF-beta precursor. The bone calvarial culture is the first example of a naturally occurring system that expresses the 100-kDa latent TGF-beta complex. C1 NCI,BETHESDA,MD 20892. BRISTOL MEYERS SQUIBB,SEATTLE,WA 98121. RP BONEWALD, LF (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV ENDOCRINOL & METAB,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. RI Oreffo, Richard/A-4615-2011 OI Oreffo, Richard/0000-0001-5995-6726 FU NIAMS NIH HHS [AR-39529, AR-39357]; NIDCR NIH HHS [DE-08569] NR 43 TC 109 Z9 111 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUN PY 1991 VL 5 IS 6 BP 741 EP 751 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FU005 UT WOS:A1991FU00500001 PM 1922093 ER PT J AU SMITH, CL HAGER, GL PIKE, JW MARX, SJ AF SMITH, CL HAGER, GL PIKE, JW MARX, SJ TI OVEREXPRESSION OF THE HUMAN VITAMIN-D3 RECEPTOR IN MAMMALIAN-CELLS USING RECOMBINANT ADENOVIRUS VECTORS SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID RAT OSTEOCALCIN GENE; THYROID-HORMONE RECEPTOR; HUMAN ESTROGEN-RECEPTOR; HIGH-LEVEL EXPRESSION; MAMMARY-TUMOR VIRUS; HUMAN GLUCOCORTICOID RECEPTOR; 1,25-DIHYDROXYVITAMIN-D3 RECEPTOR; SACCHAROMYCES-CEREVISIAE; DNA-BINDING; INVITRO TRANSCRIPTION AB The human vitamin D3 receptor (hVDR) cDNA was cloned into the E1 region of the adenovirus genome to generate recombinant viruses which were used to infect 293 (adenovirus-transformed human fetal kidney) cells. High salt extracts from cells infected with the recombinant viruses were subjected to immunoblot analysis using a monoclonal antibody to chicken VDR and were shown to contain large quantities of a protein of approximately 50 kDa with a migration identical to that of the hVDR in T47D (human mammary adenocarcinoma) cells. Scatchard analysis showed that the infected cells express approximately 100-fold more receptor than T47D cells and that this receptor binds 1,25-dihydroxyvitamin D3 with high affinity. The overexpressed hVDR also binds to DNA-cellulose and is eluted with a KCI concentration similar to that determined for fully active endogenous VDR. Nuclear extracts from cells infected with the hVDR-expressing adenoviruses contain an activity that specifically binds an oligonucleotide with sequences from the rat osteocalcin vitamin D3 response element, as determined by gel mobility shift. This interaction can be inhibited by the presence of an anti-VDR antibody, but not by nonspecific immunoglobulins. We conclude, therefore, that the overexpressed receptor has the ligand- and DNA-binding characteristics defined for endogenous VDR and that adenoviruses can be used to efficiently express large quantities of functional hVDR in a human cell line. Finally, a second binding activity, specific for the vitamin D response element, but distinct from the VDR, has been identified in extracts from uninfected cells. C1 NCI,EXPTL CARCINOGENESIS LAB,HORMONE ACT & ONCOGENESIS SECT,BETHESDA,MD 20892. BAYLOR UNIV,DEPT PEDIAT,HOUSTON,TX 77030. BAYLOR UNIV,DEPT CELL BIOL,HOUSTON,TX 77030. RP SMITH, CL (reprint author), NIDDKD,MINERAL METAB SECT,METAB DIS BRANCH,BLDG 10,ROOM 9C101,9000 ROCKVILLE PK,BETHESDA,MD 20892, USA. NR 62 TC 22 Z9 22 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUN PY 1991 VL 5 IS 6 BP 867 EP 878 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FU005 UT WOS:A1991FU00500016 PM 1656244 ER PT J AU HOOK, WA ZINSSER, FU BERENSTEIN, EH SIRAGANIAN, RP AF HOOK, WA ZINSSER, FU BERENSTEIN, EH SIRAGANIAN, RP TI MONOCLONAL-ANTIBODIES DEFINING EPITOPES ON HUMAN IGE SO MOLECULAR IMMUNOLOGY LA English DT Article ID EPSILON-CHAIN FRAGMENT; BOUND IMMUNOGLOBULIN-E; BASOPHILIC LEUKEMIA-CELLS; ANTIGEN-SPECIFIC HYBRIDOMAS; RAT MAST-CELLS; ESCHERICHIA-COLI; BINDING-SITE; RECEPTOR COMPLEXES; FC-RECEPTOR; SOLUBLE IGE AB Twelve monoclonal antibodies (mAb) were isolated that bound to six clusters of epitopes on the constant region of the epsilon chain of human IgE. Four of the mAb bound to the C-epsilon-1 or early C-epsilon-2 regions; three of these bound to the IgE myeloma protein PS and to serum IgE but not to the IgE myeloma protein ND. These mAb probably recognize an allotypic marker. Another mAb reacted with heat-denatured, but not native IgE. Four of the mAb failed to release histamine; the epitopes recognized by these mAb are in the C-epsilon-1, C-epsilon-2 and C-epsilon-3-4 regions of IgE. Three of these non-histamine releasing mAb did not bind to IgE on the basophil surface. These mAb recognize epitopes in C-epsilon-2 and C-epsilon-3-4 that are not accessible when IgE is bound to its receptor. Four mAb inhibited IgE binding to basophils; two of these did not release histamine, and two others that bind to epitopes in the C-epsilon-2-4 domain, released histamine and therefore blocked IgE binding by steric hindrance. Inhibition of IgE binding by different mAb suggest that the Fc-epsilon-RI and Fc-epsilon-RII bind to partly overlapping regions of the IgE molecule although the sites do not appear to be identical. A number of sites on C-epsilon-1 and C-epsilon-3-4 were accessible when IgE is bound to its basophil receptor. The data support the concept that only part of the Fc portion of IgE is hidden in the receptor and that portions of C-epsilon-1-4 are accessible on the cell surface. These mAb should be useful in determining the domains of IgE that are critical for its biological activity. RP HOOK, WA (reprint author), NIDR,IMMUNOL LAB,CLIN IMMUNOL SECT,BETHESDA,MD 20892, USA. NR 41 TC 17 Z9 19 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JUN PY 1991 VL 28 IS 6 BP 631 EP 639 DI 10.1016/0161-5890(91)90132-4 PG 9 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA FY069 UT WOS:A1991FY06900008 PM 1713647 ER PT J AU STOJILKOVIC, SS IIDA, T MERELLI, F CATT, KJ AF STOJILKOVIC, SS IIDA, T MERELLI, F CATT, KJ TI CALCIUM SIGNALING AND SECRETORY RESPONSES IN ENDOTHELIN-STIMULATED ANTERIOR-PITUITARY-CELLS SO MOLECULAR PHARMACOLOGY LA English DT Article ID VASCULAR SMOOTH-MUSCLE; GROWTH-HORMONE SECRETION; INTRACELLULAR CALCIUM; VASOCONSTRICTOR PEPTIDE; CYTOSOLIC CALCIUM; RAT HYPOTHALAMUS; RELEASE; MOBILIZATION; OSCILLATIONS; RECEPTORS AB Endothelin (ET) receptors are present in pituitary cells and stimulate hormone release through the phosphoinositide/Ca2+ signaling system. In pituitary cell suspensions, ET caused [Ca2+]i elevations of much higher amplitudes than those induced by other vasoactive hormones, including angiotensin II, vasopressin, and noradrenalin. The action of ET was coupled to rapid and transient activation of exocytosis in gonadotrophs, thyrotrophs, somatotrophs, and lactotrophs. In contrast, angiotensin II did not stimulate luteinzing hormone release, and luteinizing hormone responses to vasopressin and noradrenalin were very small. Single gonadotrophs exhibited three types of [Ca2+]i responses to increasing doses of ET, (a) subthreshold responses, with amplitude modulation; (b) threshold-oscillatory responses, with frequency modulation; and (c) threshold-biphasic responses, as the summation of single Ca2+ spikes. The same [Ca2+]i patterns were also seen in gonadotropin-releasing hormone (GnRH)-stimulated cells. In the presence of [Ca2+]e, the amplitudes of the Ca2+ spikes progressively decreased during continuous stimulation with ET or GnRH, reaching the nonoscillatory plateau level after 200-400 sec of stimulation. In cells stimulated with GnRH, subsequent exposure to ET, GnRH, or ionomycin during the plateau phase did not elicit further increases in [Ca2+]i, whereas cells stimulated with ET responded partially to all three agents. In addition, cells exposed to ET or GnRH for 30 min, followed by a 30-min recovery period, were able to mount a full [Ca2+]i response to GnRH, but not to ET-1. Similarly, both peptides elicited rapid increases in LH release, with comparable potencies, but the response to ET decreased much more rapidly during sustained stimulation and gonadotrophs became refractory to further ET stimulation. This is in part attributable to rapid endocytosis of ET receptors during continuous agonist stimulation. These data indicate that ET exerts potent but transient secretory actions in several pituitary cell types and is a potential regulator of gonadotropin release. The initial receptor-coupling events in both ET- and GnRH-stimulated cells are similar, but the differences observed during continuous or repetitive stimulation indicate that the ET receptor pathway undergoes rapid desensitization that is critical in determining the distinct cellular responses to the two peptides. RP STOJILKOVIC, SS (reprint author), NICHHD,ENDOCRINOL & REPROD RES BRANCH,BLDG 10,ROOM B1-L400,BETHESDA,MD 20892, USA. NR 25 TC 56 Z9 56 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUN PY 1991 VL 39 IS 6 BP 762 EP 770 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FQ961 UT WOS:A1991FQ96100011 PM 1646950 ER PT J AU NAIR, PP SHAMI, S SAINZ, E JUDD, JT TAYLOR, PR SCHATZKIN, A AF NAIR, PP SHAMI, S SAINZ, E JUDD, JT TAYLOR, PR SCHATZKIN, A TI QUANTITATIVE ASSESSMENT OF THE GENOTOXICITY OF FECAPENTAENES SO MUTATION RESEARCH LA English DT Article DE FECAPENTAENE; MUTAGENS; SOS CHROMOTEST ID COLORIMETRIC BACTERIAL ASSAY; SOS CHROMOTEST; HUMAN FECES; ESCHERICHIA-COLI; POTENT MUTAGEN; DNA AB Fecapentaenes are a group of fecal mutagens of microbial origin isolated from human stools. Fecapentaene-12 (F-12) and fecapentaene-14 (F-14), differing only in two carbon atoms in the side chain, are glyceryl ethers with a highly reactive chromophoric aliphatic side chain incorporating a conjugated pentaene moiety. Although these compounds are known for their genotoxicity, no test systems have been developed to precisely assess their relative genotoxicity. In this study F-12 and F-14 were assayed for their genotoxicity using the SOS Chromotest in which the induction of beta-galactosidase in E. coli PQ37 was used as a quantitative measure of biological activity. The activity obtained with F-12 and F-14 was compared with that of 4-nitroquinoline oxide (4-NQO) as the reference standard of a direct acting mutagen. While F-14 was almost as active as 4-NQO, F-12 was only about 25% as active as F-14, the higher analog. C1 NCI,DIV CANC PREVENT & CONTROL,CANC PREVENT STUDIES BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT BIOCHEM,BALTIMORE,MD 21205. RP NAIR, PP (reprint author), USDA ARS,BELTSVILLE AGR RES CTR,BELTSVILLE HUMAN NUTR RES CTR,LIPID NUTR LAB,BLDG 308,BELTSVILLE,MD 20705, USA. NR 22 TC 13 Z9 13 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD JUN PY 1991 VL 260 IS 2 BP 153 EP 157 DI 10.1016/0165-1218(91)90003-5 PG 5 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA FR982 UT WOS:A1991FR98200003 PM 1904547 ER PT J AU RAY, PE RULEY, EJ BERNARDINI, R SAAVEDRA, JM AF RAY, PE RULEY, EJ BERNARDINI, R SAAVEDRA, JM TI CHRONIC SODIUM OR CHLORIDE DEPLETION UP-REGULATES ANGIOTENSIN-II RECEPTORS IN THE ANTERIOR-PITUITARY LOBE OF YOUNG-RATS SO NEUROENDOCRINOLOGY LA English DT Article DE RENIN ANGIOTENSIN SYSTEM; PROLACTIN; CORTICOSTERONE; EXTRACELLULAR FLUID VOLUME ID PROLACTIN-RELEASE; SUBFORNICAL ORGAN; GROWTH-HORMONE; BRAIN PASTE; ALDOSTERONE; PLASMA; RENIN; RADIOIMMUNOASSAY; AUTORADIOGRAPHY; DEPRIVATION AB The effect of chronic (35 days) and selective sodium or chloride depletion on the regulation of angiotensin II receptors in the anterior pituitary gland of young male rats was studied by quantitative autoradiography. Both chronic sodium or chloride depletion produced significant extracellular fluid volume contraction, stimulation of the circulating renin-angiotensin system and increased the number of angiotensin II receptors in the anterior pituitary gland. Changes in angiotensin II receptors in both sodium- and chloride-depleted animals were associated with increased plasma prolactin levels. Our results suggest a participation of the pituitary renin-angiotensin system in the physiological response and/or possible adaptation to chronic sodium or chloride depletion. Extracellular fluid volume contraction and profound chronic stimulation of the circulating renin-angiotensin system may contribute to regulate anterior pituitary angiotensin II receptors and may influence prolactin release. C1 NIMH,CLIN SCI LAB,PHARMACOL SECT,BLDG 10,ROOM 2D-45,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,DEPT NEPHROL,WASHINGTON,DC. OI bernardini, renato/0000-0002-4765-0663 NR 34 TC 5 Z9 5 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD JUN PY 1991 VL 53 IS 6 BP 556 EP 561 DI 10.1159/000125774 PG 6 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA FR642 UT WOS:A1991FR64200004 PM 1876234 ER PT J AU BAGDY, G CHROUSOS, GP CALOGERO, AE AF BAGDY, G CHROUSOS, GP CALOGERO, AE TI CIRCADIAN PATTERNS OF PLASMA-IMMUNOREACTIVE CORTICOTROPIN, BETA-ENDORPHIN, CORTICOSTERONE AND PROLACTIN AFTER IMMUNONEUTRALIZATION OF CORTICOTROPIN-RELEASING HORMONE SO NEUROENDOCRINOLOGY LA English DT Article DE CORTICOTROPIN-RELEASING HORMONE IMMUNONEUTRALIZATION; CIRCADIAN RHYTHM; ADRENOCORTICOTROPIN; BETA-ENDORPHIN; CORTICOSTERONE; PROLACTIN; DEXAMETHASONE ID DEXAMETHASONE SUPPRESSION TEST; PITUITARY-ADRENAL AXIS; CONSCIOUS RATS; CORTISOL TREATMENT; ACTH-SECRETION; INHIBITION; STRESS; ADRENOCORTICOTROPIN; MECHANISMS; ACTIVATION AB To study the role of corticotropin-releasing hormone (CRH) in the circadian rhythm of circulating corticotropin (ACTH), beta-endorphin (beta-END), corticosterone, and prolactin (PRL), we measured the effects of CRH immunoneutralization over a 24-hour period in chronically cannulated, conscious, freely moving, male Sprague-Dawley rats, maintained at a constant light-dark cycle. Blood samples were collected in the morning (08.00 h), at noon (12.00 h), and in the evening (18.00 h) on the day of treatment, and in the morning (08.00 h) of the next day. Hyperimmune rabbit serum raised against rat CRH (1.0 ml/rat, i.v.) or normal rabbit serum (NRS, 1.0 ml/rat, i.v.) was administered at 08.00 h, immediately after the first blood sample had been collected. CRH immunoneutralization caused no significant decreases in circulating immunoreactive ACTH, beta-END and corticosterone plasma levels at noon, but abolished the evening rises of these hormones. PRL levels were not significantly different between the groups at any time point measured. To compare the effects of CRH immunoneutralization to those of glucocorticoid negative feedback, we measured the effects of dexamethasone (0.5 mg/kg, i.v. at 08.00 h) on the above parameters. ACTH and beta-END concentrations were significantly decreased, and corticosterone and PRL levels were markedly suppressed after glucocorticoid administration both at 12.00 and 18.00 h. However, 24 h after the administration of dexamethasone, PRL concentrations were elevated despite persistently low corticosterone levels. These data suggest that evening elevations of ACTH, beta-END, and corticosterone depend on release of endogenous CRH, while CRH does not appear to play a significant role in maintaining baseline ACTH and beta-END levels in the morning, and resting PRL levels throughout the day. C1 NICHHD,DEV ENDOCRINOL BRANCH,10-10N262,BETHESDA,MD 20892. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. OI Bagdy, Gyorgy/0000-0001-8141-3410 NR 43 TC 22 Z9 22 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD JUN PY 1991 VL 53 IS 6 BP 573 EP 578 DI 10.1159/000125776 PG 6 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA FR642 UT WOS:A1991FR64200006 PM 1652109 ER PT J AU SILBERSTEIN, SD MERRIAM, GR AF SILBERSTEIN, SD MERRIAM, GR TI ESTROGENS, PROGESTINS, AND HEADACHE SO NEUROLOGY LA English DT Review ID MENSTRUAL MIGRAINE; PREMENSTRUAL-SYNDROME; ORAL-CONTRACEPTIVES; DOUBLE-BLIND; PERCUTANEOUS ESTRADIOL; ATTEMPTED PROPHYLAXIS; WITHDRAWAL MIGRAINE; BETA-ENDORPHIN; DURA MATER; PROLACTIN C1 TEMPLE UNIV,HLTH SCI CTR,SCH MED,PHILADELPHIA,PA 19140. NICHHD,BETHESDA,MD 20892. RP SILBERSTEIN, SD (reprint author), GERMANTOWN HOSP & MED CTR,CTR COMPREHENS HEADACHE,1 PENN BLVD,PHILADELPHIA,PA 19144, USA. NR 132 TC 109 Z9 109 U1 0 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 1991 VL 41 IS 6 BP 786 EP 793 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA FR075 UT WOS:A1991FR07500010 PM 2046918 ER PT J AU FRANCAVILLA, TL MILETICH, RS DEMICHELE, D PATRONAS, NJ OLDFIELD, EH WEINTRAUB, BD DICHIRO, G AF FRANCAVILLA, TL MILETICH, RS DEMICHELE, D PATRONAS, NJ OLDFIELD, EH WEINTRAUB, BD DICHIRO, G TI POSITRON EMISSION TOMOGRAPHY OF PITUITARY MACROADENOMAS - HORMONE PRODUCTION AND EFFECTS OF THERAPIES SO NEUROSURGERY LA English DT Article DE HORMONE SECRETION; PITUITARY MACROADENOMA; PHARMACOLOGICAL THERAPY; POSITRON EMISSION TOMOGRAPHY; RADIATION THERAPY ID CEREBRAL GLUCOSE-UTILIZATION; ACTING SOMATOSTATIN ANALOG; F-18 FLUORODEOXYGLUCOSE; BROMOCRIPTINE THERAPY; FOLLOW-UP; ADENOMAS; TUMORS; PET; SMS-201-995; METABOLISM AB Positron emission tomography with [F-18]fluorodeoxyglucose (FDG) was carried out in 24 patients with pituitary macro-adenomas (32 studies) to assess the glucose utilization of these tumors in vivo. The adenoma metabolic index, which is the ratio of FDG uptake of tumor to a whole brain slice, was calculated. Comparisons were made between tumor uptake of FDG and hormone secretion and response to therapies. In each positron emission tomography study, the macroadenoma could be easily identified visually as an area of increased FDG uptake near the region of the sella. FDG uptakes were highest for nonfunctional adenomas, and the prolactin, growth hormone, and thyroid-stimulating hormone-producing groups displayed similar levels of glucose metabolism. The adenoma metabolic index for all tumors averaged 1.3, ranging from 0.3 for a thyroid-stimulating hormone adenoma to 3.5 for a nonfunctional tumor. Tumors did not exhibit metabolic rates that could characterize the type of hormone produced. Recurrent macroadenomas displayed metabolism similar to tumors not operated on, whereas irradiated adenomas showed lower glucose uptake than nonirradiated tumors. Drug therapy with bromocriptine or the long-acting somatostatin analogue octreotide also decreased the glucose utilization of the tumor. There was no correlation between the amount of hormone produced and the adenoma metabolic index when a group of tumors was analyzed. Patients scanned more than once, however, demonstrated changes in hormone levels that changed or did not change in parallel with tumor metabolism. Thus, positron emission tomography offers the potential capability for predicting and defining the growth of pituitary adenomas. This may be of particular value when plasma hormone assays and conventional imaging techniques prove inadequate for monitoring patient response to therapy. C1 NINCDS,NEUROIMAGING SECT,9000 ROCKVILLE PIKE,BLDG 10-1C 451,BETHESDA,MD 20892. NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,DEPT NEUROSURG,WASHINGTON,DC 20052. NIDDKD,CTR CLIN,DEPT DIAGNOST RADIOL,BETHESDA,MD. NR 43 TC 35 Z9 38 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUN PY 1991 VL 28 IS 6 BP 826 EP 833 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA FM733 UT WOS:A1991FM73300007 PM 2067604 ER PT J AU MURPHY, VA ROSENBERG, JM SMITH, QR RAPOPORT, SI AF MURPHY, VA ROSENBERG, JM SMITH, QR RAPOPORT, SI TI ELEVATION OF BRAIN MANGANESE IN CALCIUM-DEFICIENT RATS SO NEUROTOXICOLOGY LA English DT Article DE MANGANESE; CALCIUM DEFICIENCY; BRAIN; FEMUR; LIVER; SERUM; RAT ID AMYOTROPHIC LATERAL SCLEROSIS; CEREBROSPINAL-FLUID CALCIUM; CHRONIC HYPOCALCEMIA; METABOLISM; ALUMINUM; HYPERCALCEMIA; DOPAMINE; DEMENTIA; MONKEYS; BARRIER AB Rats, 3 weeks of age, consumed diets low or normal in calcium (Ca) with or without supplemental manganese (Mn) as Mn (II) acetate in drinking water. After 6 weeks, the animals were killed and [Mn] was determined in 8 brain regions, spinal cord, liver, serum, kidney, femur, and skeletal muscle. Serum [Mn] increased 1.5-, 4-, and 40-fold respectively, in normal Ca-supplemented Mn rats, low Ca rats, and low Ca-supplemented Mn rats. Elevation of tissue [Mn] occurred in all experimental groups with the greatest changes in the low Ca-extra Mn group: 6-12 fold in brain and spinal cord, and 2.5-140 fold in muscle, liver, kidney, and femur. Ratios of serum [Mn]/tissue [Mn] decreased as serum [Mn] increased suggesting saturable distribution. The findings suggest that Ca deficiency may cause Mn neurotoxicity by increasing dietary Mn absorption and brain [Mn]. RP MURPHY, VA (reprint author), NIA,NEUROSCI LAB,BLDG 10,ROOM 6C103,BETHESDA,MD 20892, USA. NR 39 TC 24 Z9 24 U1 0 U2 0 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SUM PY 1991 VL 12 IS 2 BP 255 EP 264 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA FP812 UT WOS:A1991FP81200009 PM 1956585 ER PT J AU SMITH, MR JARAMILLO, M TUAZON, PT TRAUGH, JA LIU, YL SONENBERG, N KUNG, HF AF SMITH, MR JARAMILLO, M TUAZON, PT TRAUGH, JA LIU, YL SONENBERG, N KUNG, HF TI MODULATION OF THE MITOGENIC ACTIVITY OF EUKARYOTIC TRANSLATION INITIATION FACTOR-4E BY PROTEIN-KINASE-C SO NEW BIOLOGIST LA English DT Article DE PROTEIN KINASE-C; TRANSLATIONAL INITIATION FACTORS; DNA SYNTHESIS; MICROINJECTION ID CAP-BINDING-PROTEIN; MESSENGER-RNA TRANSLATION; DIFFERENTIAL STIMULATION; PHOSPHORYLATION SITE; 5'-TERMINAL CAP; PHORBOL ESTERS; HELA-CELLS; TRANSFORMATION; MICROINJECTION; ONCOGENE C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. UNIV CALIF RIVERSIDE,DEPT BIOCHEM,RIVERSIDE,CA 92521. MCGILL UNIV,MCGILL CANC CTR,MONTREAL H3G 1Y6,QUEBEC,CANADA. MCGILL UNIV,DEPT BIOCHEM,MONTREAL H3G 1Y6,QUEBEC,CANADA. FU NCI NIH HHS [N01-CO-74102]; NIGMS NIH HHS [GM21424] NR 38 TC 27 Z9 27 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4674 J9 NEW BIOL PD JUN PY 1991 VL 3 IS 6 BP 601 EP 607 PG 7 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA GK721 UT WOS:A1991GK72100011 PM 1911648 ER PT J AU KUO, SS MELLENTIN, JD COPELAND, NG GILBERT, DJ JENKINS, NA CLEARY, ML AF KUO, SS MELLENTIN, JD COPELAND, NG GILBERT, DJ JENKINS, NA CLEARY, ML TI STRUCTURE, CHROMOSOME MAPPING, AND EXPRESSION OF THE MOUSE LYL-1 GENE SO ONCOGENE LA English DT Article ID T-CELL LEUKEMIA; DNA-BINDING DOMAIN; HEMATOPOIETIC-CELLS; PROTO-ONCOGENE; C-JUN; PRE-B; TRANSLOCATION; DIFFERENTIATION; PROTEINS; CLONING AB The mouse Lyl-1 gene was cloned and shown to consist of four exons with extensive nucleotide and structural homology to the human LYL1 gene. The Lyl-1 gene was localized to the central region of mouse chromosome 8 which defines a new region of synteny with human chromosome 19p. The predicted mouse Lyl-1 protein is 78% identical to human LYL1. The region of highest similarity occurs in the basic DNA binding and helix-loop-helix dimerization motifs which are nearly identical in mouse and man differing by only one conservative amino acid substitution. Expression of the Lyl-1 gene was found to be low in murine spleen and undetectable in other tissues by Northern blot analysis. In lymphoid cell lines, Lyl-1 was expressed in most B lineage cells but downregulated during terminal differentiation and was not expressed in most T lineage cells. In a human T ALL cell line carrying a translocation that juxtaposed LYL1 with the beta TCR gene, the translocated LYL1 gene was transcriptionally active whereas the nontranslocated gene was transcriptionally silent. We conclude that LYL1 has the properties of a lineage- and differentiation-specific HLH protein that contributes to T-cell neoplasia through its deregulated expression following chromosomal translocation. C1 NCI,FREDERICK CANC RES FACIL & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RP KUO, SS (reprint author), STANFORD UNIV,MED CTR,SCH MED,DEPT PATHOL,EXPTL ONCOL LAB,STANFORD,CA 94305, USA. FU NCI NIH HHS [N01-CO-74101, CA42971, 5T32 CA09302] NR 42 TC 46 Z9 49 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN PY 1991 VL 6 IS 6 BP 961 EP 968 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA GU622 UT WOS:A1991GU62200010 PM 2067848 ER PT J AU LUDLOW, CL NAUNTON, RF TERADA, S ANDERSON, BJ AF LUDLOW, CL NAUNTON, RF TERADA, S ANDERSON, BJ TI SUCCESSFUL TREATMENT OF SELECTED CASES OF ABDUCTOR SPASMODIC DYSPHONIA USING BOTULINUM TOXIN INJECTION SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID SPASTIC DYSPHONIA; MUSCLE AB Ten patients with abductor spasmodic dysphonia, who exhibited spasmodic bursts and heightened activity of the cricothyroid muscle during speech, were selected for participation. Between 5 and 20 U of botulinum toxin type A were injected into both right and left cricothyroid muscles. Six patients benefited substantially, whereas four did not. Acoustic analyses of voice patterns showed similar changes to the clinical impressions. Significant group improvements were found in sentence duration while selected patients improved in the proportion of their speech that was voiced and the duration of their voiceless consonants. Those patients with abductor spasmodic dysphonia and other muscle abnormalities in addition to the cricothyroid and with constant breathiness did not benefit. RP LUDLOW, CL (reprint author), NIDCD,SPEECH & VOICE UNIT,BLDG 10,ROOM 5D38,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Ludlow, Christy/0000-0002-2015-6171 NR 14 TC 38 Z9 38 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JUN PY 1991 VL 104 IS 6 BP 849 EP 855 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA FQ301 UT WOS:A1991FQ30100014 PM 1908979 ER PT J AU BENNETT, GJ AF BENNETT, GJ TI THE ROLE OF THE SYMPATHETIC NERVOUS-SYSTEM IN PAINFUL PERIPHERAL NEUROPATHY SO PAIN LA English DT Editorial Material ID DISORDERS; NEUROMA; RAT RP BENNETT, GJ (reprint author), NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892, USA. NR 13 TC 38 Z9 40 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JUN PY 1991 VL 45 IS 3 BP 221 EP 223 DI 10.1016/0304-3959(91)90045-Y PG 3 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA FT962 UT WOS:A1991FT96200001 PM 1652117 ER PT J AU BENNETT, GJ MAX, MB AF BENNETT, GJ MAX, MB TI TISSUE DONORS - PAINFUL NERVE LESIONS AND REFLEX SYMPATHETIC DYSTROPHY SO PAIN LA English DT Letter RP BENNETT, GJ (reprint author), NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JUN PY 1991 VL 45 IS 3 BP 331 EP 331 DI 10.1016/0304-3959(91)90058-6 PG 1 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA FT962 UT WOS:A1991FT96200014 PM 1876442 ER PT J AU MOFENSON, LM BURNS, DN AF MOFENSON, LM BURNS, DN TI PASSIVE-IMMUNIZATION TO PREVENT MOTHER-INFANT TRANSMISSION OF HUMAN-IMMUNODEFICIENCY-VIRUS - CURRENT ISSUES AND FUTURE-DIRECTIONS SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE PEDIATRIC ACQUIRED IMMUNODEFICIENCY SYNDROME; MOTHER-INFANT TRANSMISSION; HUMAN IMMUNODEFICIENCY VIRUS; PASSIVE IMMUNOTHERAPY ID ENVELOPE GLYCOPROTEIN GP120; AIDS-RELATED COMPLEX; NEUTRALIZING ANTIBODIES; CHILDREN BORN; CELLULAR CYTOTOXICITY; MATERNAL ANTIBODIES; MONOCLONAL-ANTIBODY; SYNTHETIC PEPTIDES; INFECTED MOTHERS; HIV-1 INFECTION RP MOFENSON, LM (reprint author), NATL INST CHILD HLTH & HUMAN DEV,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,BETHESDA,MD, USA. OI Mofenson, Lynne/0000-0002-2818-9808 NR 48 TC 19 Z9 19 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JUN PY 1991 VL 10 IS 6 BP 456 EP 462 DI 10.1097/00006454-199106000-00009 PG 7 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA FQ026 UT WOS:A1991FQ02600009 PM 1712936 ER PT J AU ABRAMS, SA ESTEBAN, NV VIEIRA, NE YERGEY, AL AF ABRAMS, SA ESTEBAN, NV VIEIRA, NE YERGEY, AL TI DUAL TRACER STABLE ISOTOPIC ASSESSMENT OF CALCIUM-ABSORPTION AND ENDOGENOUS FECAL EXCRETION IN LOW-BIRTH-WEIGHT INFANTS SO PEDIATRIC RESEARCH LA English DT Article ID HUMAN-MILK; VITAMIN-D; FORMULA; PHOSPHORUS; METABOLISM; RETENTION; NUTRIENT; BALANCE AB Using a dual tracer (Ca-44 orally and Ca-46 i.v.) stable isotope technique, true dietary Ca absorption, endogenous fecal Ca excretion, and net Ca retention were measured in 12 low birth weight (1426 +/- 260 g) infants fed a high Ca-containing formula. Endogenous fecal Ca excretion averaged 7.2 +/- 4.1% of intake, and exceeded 10% of intake in three infants. Net Ca retention, 103 +/- 38 mg/kg/d, was consistent with previous studies of Ca retention obtained using mass balance techniques and correlated closely (r = 0.98, p < 0.001) with true Ca absorption but not with endogenous fecal excretion (r = -0.40, p = 0.19). Although endogenous fecal excretion may represent a significant source of Ca loss for some low birth weight infants, these data suggest that net Ca retention in low birth weight infants fed a high Ca-containing formula is primarily determined by the total dietary Ca absorbed. C1 HOLY CROSS HOSP,SILVER SPRING,MD 20510. CHILDRENS NATL MED CTR,WASHINGTON,DC 20010. RP ABRAMS, SA (reprint author), NICHHD,THEORET & PHYS BIOL LAB,BLDG 10,RM 6C-101,BETHESDA,MD 20892, USA. OI Abrams, Steven/0000-0003-4972-9233 NR 28 TC 51 Z9 51 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD JUN PY 1991 VL 29 IS 6 BP 615 EP 618 DI 10.1203/00006450-199106010-00018 PG 4 WC Pediatrics SC Pediatrics GA FN055 UT WOS:A1991FN05500018 PM 1866219 ER PT J AU SCHEIDT, PC GRAUBARD, BI NELSON, KB HIRTZ, DG HOFFMAN, HJ GARTNER, LM BRYLA, DA AF SCHEIDT, PC GRAUBARD, BI NELSON, KB HIRTZ, DG HOFFMAN, HJ GARTNER, LM BRYLA, DA TI INTELLIGENCE AT 6 YEARS IN RELATION TO NEONATAL BILIRUBIN LEVEL - FOLLOW-UP OF THE NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN-DEVELOPMENT CLINICAL-TRIAL OF PHOTOTHERAPY SO PEDIATRICS LA English DT Article DE PHOTOTHERAPY; IQ; NEONATAL HYPOBILIRUBINEMIA ID PREMATURE INFANTS; PRETERM INFANTS; HYPERBILIRUBINEMIA; KERNICTERUS; AGE AB Results of the National Institute of Child Health and Human Development Randomized Controlled Trial of Phototherapy were examined for the relationship of neonatal bilirubin level to neurological and developmental outcome at 6-year follow-up. This analysis focused on 224 control children with birth weight of less than 2000 g. Bilirubin levels were maintained below previously specified levels by the use of exchange transfusion only (24%). Rates of cerebral palsy were not significantly higher for children with elevated maximum bilirubin level than for those whose level remained low. No association was evident between maximum bilirubin level and IQ (Full Scale, Verbal, or Performance) by simple correlation analysis (r = -.087, P = .2 for Full Scale) or by multiple linear regression adjusting for factors that covary with IQ (beta = -.15, P = .58). IQ was not associated with mean bilirubin level, time and duration of exposure to bilirubin, or measures of bilirubin-albumin binding. Thus, over the range of bilirubin levels permitted in this clinical trial, there was no evidence of bilirubin toxicity to the central nervous system. Measures used to control the level of bilirubin in low birth weight neonates appear to prevent effectively the risk of bilirubin-induced neurotoxicity. C1 NINCDS,DEV NEUROL BRANCH,BETHESDA,MD 20892. NINCDS,NEUROEPIDEMIOL BRANCH,BETHESDA,MD 20892. NICHHD,CTR RES MOTHERS & CHILDREN,HUMAN LEARNING & BEHAV BRANCH,BETHESDA,MD 20892. NICHHD,PREVENT RES PROGRAM,BIOMETRY BRANCH,BETHESDA,MD 20892. UNIV CHICAGO,DEPT PEDIAT,CHICAGO,IL 60637. NR 35 TC 45 Z9 46 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUN PY 1991 VL 87 IS 6 BP 797 EP 805 PG 9 WC Pediatrics SC Pediatrics GA FP364 UT WOS:A1991FP36400001 PM 2034482 ER PT J AU MALLOY, MH GRAUBARD, B MOSS, H MCCARTHY, M GWYN, S VIETZE, P WILLOUGHBY, A RHOADS, GG BERENDES, H AF MALLOY, MH GRAUBARD, B MOSS, H MCCARTHY, M GWYN, S VIETZE, P WILLOUGHBY, A RHOADS, GG BERENDES, H TI HYPOCHLOREMIC METABOLIC ALKALOSIS FROM INGESTION OF A CHLORIDE-DEFICIENT INFANT FORMULA - OUTCOME 9 AND 10 YEARS LATER SO PEDIATRICS LA English DT Article DE HYPOCHLOREMIC METABOLIC ALKALOSIS; SOY-BASED FORMULAS; CHLORIDE-DEFICIENT FORMULAS; INFANT NUTRITION; CHILD DEVELOPMENT; LANGUAGE DEVELOPMENT ID NEO-MULL-SOY; CHILDREN AB In 1978 and 1979 two infant formulas, Neo-Mull-Soy and Cho-Free, were found to be deficient in chloride. The Centers for Disease Control received reports that hypochloremic metabolic alkalosis (HMA) had developed in 141 children as a result of exposure to these formulas. Thirty-five of these children were examined at 9 and 10 years of age and compared with a group of 32 children who were exposed to the chloride-deficient formulas but were not reported to experience HMA and a group of 61 children who received chloride-sufficient soy formulas in infancy. The control children were matched to the HMA children on sex, race, age, and maternal education. Growth characteristics, performance on the Wechsler Intelligence Scale for Children-Revised (WISC-R), the Boston Naming Test, the Rey-Osterrieth Test, the Clinical Evaluation of Language Fundamentals-Revised (CELF-R), and subtests from several other speech and language tests were compared across the groups. After adjustment for family income and the level of the father's education, significantly lower scores were observed in the HMA children on the WISC-R Arithmetic subtest (mean = 10.5) compared with the soy control children (mean = 12.0, P < .05) and on the WISC-R Coding subtest (mean = 9.0) compared with the soy control children (mean = 10.8, P < .01). All the WISC-R subtest scores were, however, within the normal range. Although no significant differences occurred on the CELF-R between groups, the risk of an HMA child falling below the range expected for a standard population was increased on the CELF-R Composite Total, Receptive, and Expressive Language scores: risk ratios = 2.14, 2.14, and 3.03 respectively. Significant differences were observed between the children exposed, both HMA and non-HMA children, and the soy control children for behavioral problems as determined by the Achenbach Childhood Behavioral Checklist. It is concluded that as a group, children with documented HMA appear to have recovered from their growth failure and have normal cognitive development. They may, however, be at risk for deficits in language skills that require expressive language abilities. C1 ROBERT WOOD JOHNSON MED SCH,DEPT ENVIRONM & COMMUNITY HLTH,PISCATAWAY,NJ. NCI,BETHESDA,MD 20892. RP MALLOY, MH (reprint author), NICHHD,EPIDEMIOL BRANCH,PRP,EXECUT PLAZA N,ROOM 640,BETHESDA,MD 20892, USA. NR 32 TC 10 Z9 10 U1 2 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUN PY 1991 VL 87 IS 6 BP 811 EP 822 PG 12 WC Pediatrics SC Pediatrics GA FP364 UT WOS:A1991FP36400003 PM 2034484 ER PT J AU WITKIN, JM WITKIN, KM AF WITKIN, JM WITKIN, KM TI EFFECTS OF SOME ANTIMUSCARINICS ALONE AND IN COMBINATION WITH CHLORDIAZEPOXIDE ON PUNISHED AND NONPUNISHED BEHAVIOR OF RATS SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE ATROPINE; BENACTYZINE; APROPHEN; PUNISHED BEHAVIOR; BEHAVIORAL EFFECTS; RATS ID CONFLICT AB Since both diphenyl-substituted antimuscarinics and benzodiazepine anxiolytic drugs have been reported to increase responding under fixed-ratio schedules of food presentation, these antimuscarinics may also have anxiolytic activity. The effects of aprophen and benactyzine on punished responding of rats, a preclinical anxiolytic durg screen, were compared with those of atropine and chlordiazepoxide. None of the antimuscarinics produced consistent overall increases in behavior suppressed by punishment, in contrast to the dose-dependent increases obtained with chlordiazepoxide. Aprophen did not potentiate the anxiolytic activity of chlordiazepoxide. However, a high dose of atropine potentiated the effects of chlordiazepoxide on punished responding. Thus the diphenyl-substituted antimuscarinics, aprophen and benactyzine, do not possess consistent or robust anxiolytic activity in this preclinical screen. The previously reported behavioral excitatory effects of these compounds may therefore be unrelated to this pharmacological action. C1 WEINBERG CONSULTING GRP INC,WASHINGTON,DC. RP WITKIN, JM (reprint author), NIDA,ADDICT RES CTR,PSYCHOBIOL LAB,DRUG DEV GRP,POB 5180,BALTIMORE,MD 21224, USA. NR 15 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 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JUN PY 1991 VL 39 IS 2 BP 453 EP 456 DI 10.1016/0091-3057(91)90207-I PG 4 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA FZ846 UT WOS:A1991FZ84600033 PM 1946585 ER PT J AU WEISS, GH MASOLIVER, J AF WEISS, GH MASOLIVER, J TI NEAREST TRAP PARTICLE DISTANCES IN A ONE-DIMENSIONAL CTRW MODEL WITH A MOBILE TRAP SO PHYSICA A-STATISTICAL MECHANICS AND ITS APPLICATIONS LA English DT Article ID STOCHASTIC TRANSPORT; NEIGHBOR DISTANCES; DENSITY AB We consider a one-dimensional system consisting of a single mobile trap and initially randomly distributed immobile particles and calculate the asymptotic behavior of the closest distance between the trap and an untrapped particle. The motion of the trap is modelled in terms of a CTRW with a fractal time pausing-time density with exponent-alpha, where 0 < alpha-less-than-or-equal-to 1. The average value of this distance is found to go like tau-alpha/2 at long times. C1 UNIV BARCELONA, DEPT FIS FONAMENTAL, E-08028 BARCELONA, SPAIN. RP NIH, BETHESDA, MD 20892 USA. RI Masoliver, Jaume/F-7198-2016 OI Masoliver, Jaume/0000-0002-5810-879X NR 15 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 EI 1873-2119 J9 PHYSICA A JI Physica A PD JUN 1 PY 1991 VL 174 IS 2-3 BP 209 EP 213 DI 10.1016/0378-4371(91)90329-B PG 5 WC Physics, Multidisciplinary SC Physics GA FU466 UT WOS:A1991FU46600001 ER PT J AU EASTLACK, ME ARVIDSON, J SNYDERMACKLER, L DANOFF, JV MCGARVEY, CL AF EASTLACK, ME ARVIDSON, J SNYDERMACKLER, L DANOFF, JV MCGARVEY, CL TI INTERRATER RELIABILITY OF VIDEOTAPED OBSERVATIONAL GAIT-ANALYSIS ASSESSMENTS SO PHYSICAL THERAPY LA English DT Article DE EDUCATION PHYSICAL THERAPIST, CLINICAL EDUCATION; GAIT; KINESIOLOGY BIOMECHANICS, GAIT ANALYSIS AB The purpose of this study was to determine the interrater reliability of videotaped observational gait-analysis (VOGA) assessments. Fifty-four licensed physical therapists with varying amounts of clinical experience served as raters. Three patients with rheumatoid arthritis who demonstrated an abnormal gait pattern served as subjects for the videotape. The raters analyzed each patient's most severely involved knee during the four subphases of stance for the kinematic variables of knee flexion and genu valgum. Raters were asked to determine whether these variables were inadequate, normal, or excessive. The temporospatial variables analyzed throughout the entire gait cycle were cadence, step length, stride length, stance time, and step width. Generalized kappa coefficients ranged from .11 to .52. Intraclass correlation coefficients (2,1) and (3,1) were slightly higher. Our results indicate that physical therapists' VOGA assessments are only slightly to moderately reliable and that improved interrater reliability of the assessments of physical therapists utilizing this technique is needed. Our data suggest that there is a need for greater standardization of gait-analysis training. C1 UNIV DELAWARE,MCKINLY LAB 309,NEWARK,DE 19716. NATL REHABILITAT HOSP,102 IRVING ST NW,WASHINGTON,DC 20010. CTR HLTH PROMOT,PORTLAND,ME 04101. HOWARD UNIV,WASHINGTON,DC 20059. NIH,WARREN G MAGNUSEN CLIN CTR,DEPT REHABILITAT MED,BETHESDA,MD 20892. BOSTON UNIV,SARGENT COLL ALLIED HLTH PROFESS,PHYS THERAPY PROGRAM,BOSTON,MA 02215. NR 19 TC 96 Z9 97 U1 0 U2 8 PU AMER PHYS THER ASSN PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 SN 0031-9023 J9 PHYS THER JI Phys. Ther. PD JUN PY 1991 VL 71 IS 6 BP 465 EP 472 PG 8 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA FP577 UT WOS:A1991FP57700009 PM 2034709 ER PT J AU ARAKI, H HAMATAKE, RK JOHNSTON, LH SUGINO, A AF ARAKI, H HAMATAKE, RK JOHNSTON, LH SUGINO, A TI DPB2, THE GENE ENCODING DNA POLYMERASE-II SUBUNIT-B, IS REQUIRED FOR CHROMOSOME-REPLICATION IN SACCHAROMYCES-CEREVISIAE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ESCHERICHIA-COLI; CELL-CYCLE; CDC2 GENE; YEAST; PURIFICATION; EXPRESSION; TRANSFORMATION; ENZYME; ALPHA; ACID AB The Saccharomyces cerevisiae DNA polymerase II holoenzyme consists of five polypeptides. The largest is the catalytic subunit, whose gene (POL2) has been cloned and sequenced. Herein we describe the cloning and sequencing of DPB2, the gene for the second largest subunit of DNA polymerase II, and the isolation of temperature-sensitive dpb2 mutations. The DNA sequence revealed an open reading frame encoding a protein of M(r) 79,461 and lacking significant sequence similarity to any protein in data bases. Disruption of DPB2 was lethal for the cell and the temperature-sensitive dpb2-1 mutant was partially defective in DNA synthesis at the restrictive temperature, indicating that the DPB2 protein is required for normal yeast chromosomal replication. Furthermore, the DNA polymerase II complex was difficult to obtain from dpb2-1 mutant cells, suggesting that a stable DNA polymerase II complex requires DPB2 and is essential for chromosomal replication. The DPB2 transcript periodically fluctuated during the cell cycle and, like those of other genes encoding DNA replication proteins, peaked at the G1/S phase boundary. C1 NIEHS,MOLEC GENET LAB,POB 12233,RES TRIANGLE PK,NC 27709. NATL INST MED RES,CELL PROPAGAT LAB,LONDON NW7 1AA,ENGLAND. NR 30 TC 85 Z9 87 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 JUN PY 1991 VL 88 IS 11 BP 4601 EP 4605 DI 10.1073/pnas.88.11.4601 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FP087 UT WOS:A1991FP08700009 PM 2052544 ER PT J AU KAJIGAYA, S FUJII, H FIELD, A ANDERSON, S ROSENFELD, S ANDERSON, LJ SHIMADA, T YOUNG, NS AF KAJIGAYA, S FUJII, H FIELD, A ANDERSON, S ROSENFELD, S ANDERSON, LJ SHIMADA, T YOUNG, NS TI SELF-ASSEMBLED B19 PARVOVIRUS CAPSIDS, PRODUCED IN A BACULOVIRUS SYSTEM, ARE ANTIGENICALLY AND IMMUNOGENICALLY SIMILAR TO NATIVE VIRIONS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE 5TH DISEASE; TRANSIENT APLASTIC CRISIS; VACCINE; ENZYME IMMUNOASSAY ID HUMAN-BONE MARROW; STRUCTURAL PROTEINS; CELLS-INVITRO; MINUTE VIRUS; REPLICATION; EXPRESSION; ANTIBODIES; INFECTION; MICE AB B19 parvovirus is pathogenic in humans, causing fifth disease, transient aplastic crisis, some cases of hydrops fetalis, and acquired pure red cell aplasia. Efforts to develop serologic assays and vaccine development have been hampered by the virus's extreme tropism for human bone marrow and the absence of a convenient culture system. We constructed recombinants containing either the major (VP2) or minor (VP1) structural proteins of B19 in a baculovirus-based plasmid, from which the polyhedrin gene had been deleted; these recombinant plasmids were used to generate recombinant infectious baculovirus. Subsequent infection of insect cells in vitro resulted in high-level expression of either B19 VP1 or VP2. Parvovirus capsids were obtained by self-assembly in cell cultures coinfected with either VP1- and VP2-containing baculoviruses or, surprisingly, VP2-containing baculoviruses alone. Empty B19 capsids composed of VP1 and VP2 could replace serum virus as a source of antigen in a conventional immunoassay for detection of either IgG or IgM antiparvovirus antibodies in human serum. Immunization of rabbits with capsids composed of VP1 and VP2 resulted in production of antisera that recognized serum parvovirus on immunoblot and neutralized parvovirus infectivity for human erythroid progenitor cells. Baculovirus-derived parvovirus antigen can substitute for scarce viral antigen in immunoassays and should be suitable as a human vaccine. C1 CENT PUBL HLTH LAB,VIRUS REFERENCE LAB,LONDON NW9 5HT,ENGLAND. CTR DIS CONTROL,RESP & ENTEROVIRUS DIS BRANCH,ATLANTA,GA 30333. RP KAJIGAYA, S (reprint author), NHLBI,CLIN HEMATOL BRANCH,CELL BIOL SECT,BETHESDA,MD 20892, USA. NR 27 TC 170 Z9 176 U1 0 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 JUN PY 1991 VL 88 IS 11 BP 4646 EP 4650 DI 10.1073/pnas.88.11.4646 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FP087 UT WOS:A1991FP08700018 PM 1711206 ER PT J AU BRANNAN, CI LYMAN, SD WILLIAMS, DE EISENMAN, J ANDERSON, DM COSMAN, D BEDELL, MA JENKINS, NA COPELAND, NG AF BRANNAN, CI LYMAN, SD WILLIAMS, DE EISENMAN, J ANDERSON, DM COSMAN, D BEDELL, MA JENKINS, NA COPELAND, NG TI STEEL-DICKIE MUTATION ENCODES A C-KIT LIGAND LACKING TRANSMEMBRANE AND CYTOPLASMIC DOMAINS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EPIDERMAL GROWTH-FACTOR; SPOTTING W LOCUS; CELL FACTOR; PROTO-ONCOGENE; MOUSE ENCODES; FACTOR-ALPHA; MAST-CELLS; SI-LOCUS; RAT; IDENTIFICATION AB Mice homozygous for the viable Sl allele steel-Dickie (Sl(d)) are sterile, severely anemic, and black-eyed white. The nature of the Sl(d) mutation was investigated at the molecular level and was found to be due to a 4.0-kilobase intragenic deletion in mast cell growth factor (MGF) genomic sequences, providing conclusive evidence that Sl encodes MGF. As a consequence of this deletion, Sl(d) is only capable of encoding a soluble truncated growth factor that lacks both transmembrane and cytoplasmic domains. Northern analysis indicates that Sl(d) mRNA is expressed at approximately wild-type levels in adult tissues, and yeast expression studies suggest that the Sl(d) protein is as biologically active as wild-type soluble MGF. These studies provide a molecular basis for explaining the Sl(d) phenotype, a description of a germ-line mutation in the transmembrane and cytoplasmic domains of a membrane-bound growth factor, and in vivo evidence for the importance of membrane-bound forms of growth factors in mammalian development. C1 IMMUNEX CORP,DEPT MOLEC BIOL,SEATTLE,WA 98101. IMMUNEX CORP,DEPT EXPTL HEMATOL,SEATTLE,WA 98101. RP BRANNAN, CI (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21701, USA. RI Norman, Robert/A-1155-2007 OI Norman, Robert/0000-0002-3118-3896 FU NCI NIH HHS [N01-CO-74101] NR 27 TC 271 Z9 273 U1 1 U2 4 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 JUN PY 1991 VL 88 IS 11 BP 4671 EP 4674 DI 10.1073/pnas.88.11.4671 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FP087 UT WOS:A1991FP08700023 PM 1711207 ER PT J AU KATZMAN, M MACK, JPG SKALKA, AM LEIS, J AF KATZMAN, M MACK, JPG SKALKA, AM LEIS, J TI A COVALENT COMPLEX BETWEEN RETROVIRAL INTEGRASE AND NICKED SUBSTRATE DNA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE COVALENT LINKAGE; RETROVIRAL DNA INTEGRATION ID ESCHERICHIA-COLI; VIRAL-DNA; PROTEIN; RECOMBINATION; INVITRO; TOPOISOMERASE; SEQUENCES; TYROSINE AB Purified retroviral integrase (IN) from avian sarcoma-leukosis viruses can appropriately process the termini of linear viral DNA, cleave host DNA in a sequence-independent manner, and catalyze integrative recombination; an exogenous source of energy is not required for these reactions. Using DNA substrates containing radioactive phosphate groups, we demonstrate that IN becomes covalently joined to the new 5' phosphate ends of DNA produced at sites of cleavage. Most of the phosphodiester linkages between IN and DNA involve serine, but some involve threonine. Computer-assisted alignment of 80 retroviral and retrotransposon IN sequences identified one serine that is conserved in all of these proteins and three less-conserved threonine residues. These results identify candidate active-site residues and provide support for the participation of a covalent IN-DNA intermediate in retroviral integration. C1 PENN STATE UNIV, MILTON S HERSHEY MED CTR, COLL MED, DEPT MED, HERSHEY, PA 17033 USA. NCI, FREDERICK CANC RES & DEV CTR, CRYSTALLOG LAB, FREDERICK, MD 21701 USA. FOX CHASE CANC INST, INST CANC RES, PHILADELPHIA, PA 19111 USA. PENN STATE UNIV, MILTON S HERSHEY MED CTR, COLL MED, DEPT MICROBIOL & IMMUNOL, HERSHEY, PA 17033 USA. CASE WESTERN RESERVE UNIV, SCH MED, DEPT BIOCHEM, CLEVELAND, OH 44106 USA. FU NCI NIH HHS [CA 06927, CA 38046, CA 49042] NR 27 TC 44 Z9 44 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN PY 1991 VL 88 IS 11 BP 4695 EP 4699 DI 10.1073/pnas.88.11.4695 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FP087 UT WOS:A1991FP08700028 PM 1647013 ER PT J AU GUTKIND, JS NOVOTNY, EA BRANN, MR ROBBINS, KC AF GUTKIND, JS NOVOTNY, EA BRANN, MR ROBBINS, KC TI MUSCARINIC ACETYLCHOLINE-RECEPTOR SUBTYPES AS AGONIST-DEPENDENT ONCOGENES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MALIGNANT; TRANSFORMATION; 2ND MESSENGERS; G-PROTEINS; NEUROTRANSMITTER ID STIMULATES DNA-SYNTHESIS; GROWTH-FACTOR RECEPTORS; A9 L-CELLS; PHOSPHOINOSITIDE HYDROLYSIS; TYROSINE PHOSPHORYLATION; SIGNALING PATHWAYS; BINDING-PROPERTIES; ADENYLYL CYCLASE; ARACHIDONIC-ACID; PERTUSSIS TOXIN AB We have evaluated the muscarinic acetylcholine family of G protein-coupled receptors (mAChRs) for their oncogenic potential. These receptors are preferentially expressed in postmitotic cells, transducing signals specified by their endogenous agonist, the neurotransmitter acetylcholine. Cells transfected with individual human mAChR genes were morphologically indistinguishable from parental NIH 3T3 cells in the absence of agonist. In contrast, when cultures were supplemented with carbachol, a stable analog of acetylcholine, foci of transformation readily appeared in m1, m3, or m5 but not in m2 or m4 mAChRs transfectants. Receptor expression was verified by ligand binding and was similar for each transfected culture. Transformation was dose-dependent and required only low levels of receptor expression. In transformation-competent cells, agonist induced phosphatidylinositol hydrolysis, whereas in m2 or m4 transfectants, receptors were coupled to the inhibition of adenylyl cyclase. These findings demonstrate that mAChRs linked to phosphatidylinositol hydrolysis can act as conditional oncogenes when expressed in cells capable of proliferation. C1 NINCDS,MOLEC BIOL LAB,BETHESDA,MD 20892. RP GUTKIND, JS (reprint author), NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892, USA. RI Gutkind, J. Silvio/A-1053-2009 NR 39 TC 268 Z9 273 U1 0 U2 3 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 JUN PY 1991 VL 88 IS 11 BP 4703 EP 4707 DI 10.1073/pnas.88.11.4703 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FP087 UT WOS:A1991FP08700030 PM 1905013 ER PT J AU ACCILI, D TAYLOR, SI AF ACCILI, D TAYLOR, SI TI TARGETED INACTIVATION OF THE INSULIN-RECEPTOR GENE IN MOUSE 3T3-L1 FIBROBLASTS VIA HOMOLOGOUS RECOMBINATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TRANSFECTION; ADIPOCYTE DIFFERENTIATION; THYMIDINE KINASE; NEOMYCIN RESISTANCE ID GROWTH FACTOR-I; GERM-LINE TRANSMISSION; EMBRYONIC STEM-CELLS; CHROMOSOMAL LOCALIZATION; RESPONSIVENESS INVITRO; INT-1 PROTOONCOGENE; HORMONE RECEPTORS; TRANSPORTER GENE; ES CELLS; ADIPOCYTES AB To study the role of the insulin receptor in determining adipocyte differentiation of the mouse cell line 3T3-L1, we have introduced a mutation that inactivates the insulin receptor gene by homologous recombination. In two independent clones, inactivation of one allele of the insulin receptor gene was associated with a 50-70% reduction in the number of insulin receptors. In addition, both clones were markedly impaired in their ability to differentiate into adipocytes. The defect in adipocyte-specific differentiation was corrected by expression of transfected human insulin receptor cDNA. These data suggest that the insulin receptor may play an important role in promoting differentiation of 3T3-L1 cells into adipocytes in vitro. C1 NIDDKD,DIABETES BRANCH,BETHESDA,MD 20892. NR 34 TC 57 Z9 57 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 JUN PY 1991 VL 88 IS 11 BP 4708 EP 4712 DI 10.1073/pnas.88.11.4708 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FP087 UT WOS:A1991FP08700031 PM 2052553 ER PT J AU SMITH, EA SELDIN, MF MARTINEZ, L WATSON, ML CHOUDHURY, GG LALLEY, PA PIERCE, J AARONSON, S BARKER, J NAYLOR, SL SAKAGUCHI, AY AF SMITH, EA SELDIN, MF MARTINEZ, L WATSON, ML CHOUDHURY, GG LALLEY, PA PIERCE, J AARONSON, S BARKER, J NAYLOR, SL SAKAGUCHI, AY TI MOUSE PLATELET-DERIVED GROWTH-FACTOR RECEPTOR-ALPHA GENE IS DELETED IN W19H AND PATCH MUTATIONS ON CHROMOSOME-5 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TYROSINE KINASE RECEPTOR; SPOTTING W LOCUS; ONCOGENE C-KIT; PROTO-ONCOGENE; PDGF RECEPTOR; MUTANT MICE; EXPRESSION; LINKAGE; LIGAND; DIFFERENTIATION AB The mouse W19H mutation is an x-ray-induced deletion of more than 2 centimorgans on chromosome 5 encompassing the white spotting mutation W (encoded by the Kit protooncogene), patch (Ph), and recessive lethal (l) loci. The platelet-derived growth factor receptor alpha-gene (PDGFRA) like Kit encodes a transmembrane receptor tyrosine kinase. By using mouse-Chinese hamster somatic cell hybrids and haplotype analysis in interspecific backcross mice, mouse Pdgfra was mapped to chromosome 5 in tight linkage with Kit. Hybridization of a PDGFRA probe to DNAs from W19H/+ heterozygous mice and patch heterozygous mice, and their wild-type littermates, demonstrated deletion of Pdgfra. Pulsed-field gel electrophoresis indicated that Kit and Pdgfra are linked on a 630-kilobase Mlu I DNA fragment. Thus the W19H deletion removes at least two receptor tyrosine kinases and the results suggest Pdgfra as a candidate for the Ph locus. C1 UNIV TEXAS,HLTH SCI CTR,DEPT CELLULAR & STRUCT BIOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284. WAYNE STATE UNIV,CTR MOLEC GENET,DETROIT,MI 48202. NCI,BETHESDA,MD 20892. JACKSON LAB,BAR HARBOR,ME 04609. DUKE UNIV,MED CTR,DURHAM,NC 27710. FU NHGRI NIH HHS [HG00101]; NIA NIH HHS [P01-AG06872]; NIDDK NIH HHS [DK27726] NR 40 TC 91 Z9 91 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 JUN PY 1991 VL 88 IS 11 BP 4811 EP 4815 DI 10.1073/pnas.88.11.4811 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FP087 UT WOS:A1991FP08700052 PM 1647018 ER PT J AU FROLOVA, EI DOLGANOV, GM MAZO, IA SMIRNOV, DV COPELAND, P STEWART, C OBRIEN, SJ DEAN, M AF FROLOVA, EI DOLGANOV, GM MAZO, IA SMIRNOV, DV COPELAND, P STEWART, C OBRIEN, SJ DEAN, M TI LINKAGE MAPPING OF THE HUMAN CSF2 AND IL3 GENES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GM-CSF; MOLECULAR-CLONING; MYELOID DISORDERS; REGULATING HEMATOPOIESIS; MURINE INTERLEUKIN-3; HUMAN CHROMOSOME-5; CYSTIC-FIBROSIS; DELETION 5Q; MULTI-CSF; INVOLVEMENT AB Interleukin 3 (encoded by the IL3 gene) and granulocyte - macrophage colony-stimulating factor (encoded by the CSF2 gene) are small secreted polypeptides that bind to specific cell surface receptors and regulate the growth, gene expression, and differentiation of many of the hematopoietic cell lineages, particularly nonlymphoid cells. The IL3 and CSF2 genes have been cloned and mapped to human chromosome bands 5q23-31. Only 10 kilobases of DNA separates the two genes, suggesting that they have a common origin and/or regulation. We have cloned 70 kilobases of genomic DNA that includes the IL3 and CSF2 genes, as well as flanking sequences, and report a physical map of this region. Several uniquesequence DNA segments have been identified in this region, and one of these fragments detects two restriction fragment length polymorphisms in DNA from unrelated Caucasians. Segregation of these DNA polymorphisms was followed in the Centre Etude' du Polymorphisme Humaine (CEPH) panel of 40 large three-generation pedigrees, and linkage was detected with 17 genetic markers previously typed in these families. Multipoint linkage analysis permits the placement of the region containing the IL3 and CSF2 structural genes on the recombination-genetic linkage map of chromosome 5q and thereby allows the role of these genes in leukemogenesis to be more critically examined. C1 DYNCORP,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. MM SHEMYAKIN BIOORGAN CHEM INST,MOSCOW 117312,USSR. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. RI Dean, Michael/G-8172-2012; Mazo, Ilya/G-6549-2014 OI Dean, Michael/0000-0003-2234-0631; Mazo, Ilya/0000-0002-8587-4895 NR 38 TC 16 Z9 16 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN PY 1991 VL 88 IS 11 BP 4821 EP 4824 DI 10.1073/pnas.88.11.4821 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FP087 UT WOS:A1991FP08700054 PM 1675789 ER PT J AU SHIRVAN, MH POLLARD, HB HELDMAN, E AF SHIRVAN, MH POLLARD, HB HELDMAN, E TI MIXED NICOTINIC AND MUSCARINIC FEATURES OF CHOLINERGIC RECEPTOR COUPLED TO SECRETION IN BOVINE CHROMAFFIN CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CATECHOLAMINE SECRETION; ADRENAL-MEDULLA; ACID RELEASE; AGONISTS; CALCIUM; BINDING AB Acetylcholine evokes release from cultured bovine chromaffin cells by a mechanism that is believed to be classically nicotinic. However, we found that the full muscarinic agonist oxotremorine-M (Oxo-M) induced a robust catecholamine (CA) secretion. By contrast, muscarine, pilocarpine, bethanechol, and McN-A-343 did not elicit any secretory response. Desensitization of the response to nicotine by Oxo-M and desensitization of the response to Oxo-M by nicotine suggest that both nicotine and Oxo-M were acting at the same receptor. Additional experiments supporting this conclusion show that nicotine-induced secretion and Oxo-M-induced secretion were similarly blocked by various muscarinic and nicotinic antagonists. Moreover, secretion induced by nicotine and Oxo-M were Ca2+ dependent, and both agonists induced Ca-45(2+) uptake. Equilibrium binding studies showed that [H-3]Oxo-M bound to chromaffin cell membranes with a K(d) value of 3.08 x 10(-8) M and a Hill coefficient of 1.00, suggesting one binding site for this ligand. Nicotine inhibited Oxo-M binding in a noncompetitive manner, suggesting that both ligands bind at two different sites on the same receptor. We propose that the receptor on bovine chromaffin cells that is coupled to secretion represents an unusual cholinergic receptor that has both nicotinic and muscarinic features. RP SHIRVAN, MH (reprint author), NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892, USA. NR 20 TC 23 Z9 23 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 JUN PY 1991 VL 88 IS 11 BP 4860 EP 4864 DI 10.1073/pnas.88.11.4860 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FP087 UT WOS:A1991FP08700062 PM 2052567 ER PT J AU MARGOSSIAN, SS KRUEGER, JW SELLERS, JR CUDA, G CAULFIELD, JB NORTON, P SLAYTER, HS AF MARGOSSIAN, SS KRUEGER, JW SELLERS, JR CUDA, G CAULFIELD, JB NORTON, P SLAYTER, HS TI INFLUENCE OF THE CARDIAC MYOSIN HINGE REGION ON CONTRACTILE ACTIVITY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SUBFRAGMENT-2; MOTILITY; SARCOMERE SHORTENING; MYOCYTES ID MUSCLE; FORCE; SUBFRAGMENT-2; ACTIN; INVITRO; ALPHA; THROMBOSPONDIN; MYOFIBRILS; ANTIBODIES; FILAMENTS AB The participation of cardiac myosin hinge in contractility was investigated by in vitro motility and ATPase assays and by measurements of sarcomere shortening. The effect on contractile activity was analyzed using an antibody directed against a 20-amino acid peptide within the hinge region of myosin. This antibody bound specifically at the hinge at a distance of 55 nm from the S1/S2 junction, was specific to human, dog, and rat cardiac myosins, did not crossreact with gizzard or skeletal myosin, and had no effect on ATPase activity of purified S1 and myofibrils. However, it completely suppressed the movement of actin filaments in in vitro motility assays and reduced active shortening of sarcomeres of skinned cardiac myocytes by half. Suppression of motion by the antihinge antibody may reflect a mechanical constraint imposed by the antibody upon the mobility of the S2 region of myosin. The results suggest that the steps in the mechanochemical energy transduction can be separately influenced through S2. C1 YESHIVA UNIV ALBERT EINSTEIN COLL MED,BRONX,NY 10461. NHLBI,MOLEC CARDIOL LAB,BETHESDA,MD 20892. UNIV ALABAMA,DEPT PATHOL,BIRMINGHAM,AL 35294. HARVARD UNIV,SCH MED,DEPT CELLULAR & MOLEC PHYSIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. MONTEFIORE MED CTR,DEPT MED & PHYSIOL BIOPHYS,BRONX,NY 10467. RP MARGOSSIAN, SS (reprint author), MONTEFIORE MED CTR,DEPT BIOCHEM & ORTHOPED RES,ORTHOPED RES LABS,111 E 210TH ST,BRONX,NY 10467, USA. RI Cuda, Giovanni/F-5359-2012 OI Cuda, Giovanni/0000-0001-6313-1866 FU NHLBI NIH HHS [HL-26569, HL23125, HL37412] NR 33 TC 26 Z9 26 U1 0 U2 3 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 JUN PY 1991 VL 88 IS 11 BP 4941 EP 4945 DI 10.1073/pnas.88.11.4941 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FP087 UT WOS:A1991FP08700079 PM 1828886 ER PT J AU BALZARINI, J HOLY, A JINDRICH, J DVORAKOVA, H HAO, Z SNOECK, R HERDEWIJN, P JOHNS, DG DECLERCQ, E AF BALZARINI, J HOLY, A JINDRICH, J DVORAKOVA, H HAO, Z SNOECK, R HERDEWIJN, P JOHNS, DG DECLERCQ, E TI 9-[(2RS)-3-FLUORO-2-PHOSPHONYLMETHOXYPROPYL] DERIVATIVES OF PURINES - A CLASS OF HIGHLY SELECTIVE ANTIRETROVIRAL AGENTS INVITRO AND INVIVO SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE 9-[(2RS)-3-FLUORO-2-PHOSPHONYLMETHOXYPROPYL]ADENINE; 9-[(2RS)-3-FLUORO-2-PHOSPHONYLMETHOXYPROPYL]-2,6-DIAMINOPURINE; HUMAN IMMUNODEFICIENCY VIRUS; REVERSE TRANSCRIPTASE; 5-PHOSPHORIBOSYL-1-PYROPHOSPHATE SYNTHETASE ID ACYCLIC NUCLEOTIDE ANALOGS; HERPES-SIMPLEX VIRUS; ANTIVIRAL ACTIVITY; SARCOMA-VIRUS; HTLV-III; 9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE; REPLICATION; INHIBITION; DIPHOSPHATES; RETROVIRUS AB A new class of compounds, 9-[(2RS)-3-fluoro-2-phosphonylmethoxypropyl] [(RS)-FPMP] derivatives of purines, is described that has selective activity against a broad spectrum of retroviruses [including human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2)] but not other RNA or DNA viruses. This activity spectrum is completely different from that of the parental compounds, 9-[(2S)-3-hydroxy-2-phosphonylmethoxypropyl] [(S)-HPMP] derivatives of purines, which are active against a broad range of DNA viruses. The racemic (RS)-FPMP derivatives of adenine and 2,6-diaminopurine, termed (RS)-FPMPA and (RS)-FPMPDAP, respectively, are markedly more selective as in vitro antiretroviral agents than their 9-(2-phosphonylmethoxyethyl) (PME) counterparts, PMEA and PMEDAP. Also, (RS)-FPMPA and (RS)-FPMPDAP have a substantially higher therapeutic index in mice in inhibiting Moloney murine sarcoma virus-induced tumor formation and associated death and are markedly less inhibitory to human bone marrow cells than PMEA and PMEDAP. The diphosphate derivative of (RS)-FPMPA [(RS)-FPMPApp] is a potent and selective inhibitor of HIV-1 reverse transcriptase but not of HSV-1 DNA polymerase or DNA polymerase-alpha. (RS)-FPMPApp, akin to PMEA diphosphate (PMEApp), acts as a DNA chain terminator. The DNA chain-terminating properties of PMEApp and (RS)-FPMPApp seem to be a prerequisite for acyclic nucleoside phosphonates to exhibit antiretrovirus (i.e., anti-HIV) activity. C1 CZECHOSLOVAK ACAD SCI, INST ORGAN CHEM & BIOCHEM, CS-11142 PRAGUE 1, CZECHOSLOVAKIA. NCI, BETHESDA, MD 20892 USA. RP BALZARINI, J (reprint author), CATHOLIC UNIV LEUVEN, REGA INST MED RES, MINDERBROEDERSSTR 10, B-3000 LOUVAIN, BELGIUM. RI Jindrich, Jindrich/A-3527-2008 OI Jindrich, Jindrich/0000-0003-3770-0214 NR 30 TC 101 Z9 101 U1 4 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN PY 1991 VL 88 IS 11 BP 4961 EP 4965 DI 10.1073/pnas.88.11.4961 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FP087 UT WOS:A1991FP08700083 PM 1711214 ER PT J AU KLOTMAN, ME KIM, S BUCHBINDER, A DEROSSI, A BALTIMORE, D WONGSTAAL, F AF KLOTMAN, ME KIM, S BUCHBINDER, A DEROSSI, A BALTIMORE, D WONGSTAAL, F TI KINETICS OF EXPRESSION OF MULTIPLY SPLICED RNA IN EARLY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION OF LYMPHOCYTES AND MONOCYTES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ALTERNATIVE SPLICING; REVERSE TRANSCRIPTASE-PCR; REGULATORY GENES; HUMAN RETROVIRUS ID HTLV-III; REGULATORY GENES; VIRAL-RNA; TAT; REPLICATION; PROTEIN; HIV-1; NEF; MUTATIONS; ACCEPTOR AB The genome of human immunodeficiency virus type 1 (HIV-1) encodes at least six proteins involved in regulation as well as the structural proteins Gag, Pol, and Env. The interplay of the various regulators generates early and late transcriptional phases in the HIV-1 life cycle; the earliest RNA is enriched in subgenomic species, and the genomic transcript appears at the later stage of infection. We investigated the nature of the mRNAs expressed in the early stages of infection when the 2 kilobase subgenomic species predominate. RNA was analyzed in the early phase of a one-step growth cycle of HIV-1 infection in T-lymphoid and monocytic cell lines by using PCR amplification of in vitro-synthesized viral cDNAs. In both cell lines, expression of Tat-, Rev-, and Nef-specific messages appeared simultaneously and could be detected within 8-12 hr of infection but in different amounts with a predominance of Nef-specific message. The Env-specific message could be detected as early as the Rev-specific message, indicating that expression of at least small amounts of the singly spliced message could occur before the accumulation of Rev. C1 NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. ROCKEFELLER UNIV,NEW YORK,NY 10021. RP KLOTMAN, ME (reprint author), NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20815, USA. RI De Rossi, Anita/L-3128-2015; klotman, mary/A-1921-2016 OI De Rossi, Anita/0000-0001-6435-7509; FU NHLBI NIH HHS [HL43510]; NIAID NIH HHS [AI30897] NR 25 TC 150 Z9 150 U1 1 U2 3 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 JUN PY 1991 VL 88 IS 11 BP 5011 EP 5015 DI 10.1073/pnas.88.11.5011 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FP087 UT WOS:A1991FP08700093 PM 1711215 ER PT J AU LAFORGIA, S MORSE, B LEVY, J BARNEA, G CANNIZZARO, LA LI, F NOWELL, PC BOGHOSIANSELL, L GLICK, J WESTON, A HARRIS, CC DRABKIN, H PATTERSON, D CROCE, CM SCHLESSINGER, J HUEBNER, K AF LAFORGIA, S MORSE, B LEVY, J BARNEA, G CANNIZZARO, LA LI, F NOWELL, PC BOGHOSIANSELL, L GLICK, J WESTON, A HARRIS, CC DRABKIN, H PATTERSON, D CROCE, CM SCHLESSINGER, J HUEBNER, K TI RECEPTOR PROTEIN-TYROSINE PHOSPHATASE-GAMMA IS A CANDIDATE TUMOR SUPPRESSOR GENE AT HUMAN-CHROMOSOME REGION 3P21 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CHROMOSOME DELETIONS TRANSLOCATIONS; LOSS OF HETEROZYGOSITY; TYROSINE PHOSPHORYLATION DEPHOSPHORYLATION; SOMATIC CELL HYBRIDS ID RENAL-CELL CARCINOMA; LUNG-CANCER; HOMOZYGOUS DELETION; DNA-SEQUENCE; SHORT ARM; FAMILY; CLONING; LOCUS; D3S3 AB PTPG, the gene for protein-tyrosine phosphatase-gamma (PTP-gamma), maps to a region of human chromosome 3, 3p21, that is frequently deleted in renal cell carcinoma and lung carcinoma. One of the functions of protein-tyrosine phosphatases is to reverse the effect of protein-tyrosine kinases, many of which are oncogenes, suggesting that some protein-tyrosine phosphatase genes may act as tumor suppressor genes. A hallmark of tumor suppressor genes is that they are deleted in tumors in which their inactivation contributes to the malignant phenotype. In this study, one PTP-gamma allele was lost in 3 of 5 renal carcinoma cell lines and 5 of 10 lung carcinoma tumor samples tested. Importantly, one PTP-gamma allele was lost in three lung tumors that had not lost flanking loci. PTP-gamma mRNA was expressed in kidney cell lines and lung cell lines but not expressed in several hematopoietic cell lines tested. Thus, the PTP-gamma gene has characteristics that suggest it as a candidate tumor suppressor gene at 3p21. C1 RHONE POULENC RORER CENT RES,KING OF PRUSSIA,PA 19406. NYU MED CTR,DEPT PHARMACOL,NEW YORK,NY 10016. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV PENN,SCH MED,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT MED,PHILADELPHIA,PA 19104. NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. UNIV COLORADO,HLTH SCI CTR,DEPT MED,DENVER,CO 80262. ELEANOR ROOSEVELT INST,DENVER,CO 80206. RP LAFORGIA, S (reprint author), TEMPLE UNIV,HLTH SCI CTR,SCH MED,FELS INST CANC RES & MOLEC BIOL,PHILADELPHIA,PA 19140, USA. FU NCI NIH HHS [CA39860, CA21124, CA42232] NR 26 TC 232 Z9 233 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 JUN PY 1991 VL 88 IS 11 BP 5036 EP 5040 DI 10.1073/pnas.88.11.5036 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FP087 UT WOS:A1991FP08700098 PM 1711217 ER PT J AU LAI, CJ ZHAO, B HORI, H BRAY, M AF LAI, CJ ZHAO, B HORI, H BRAY, M TI INFECTIOUS RNA TRANSCRIBED FROM STABLY CLONED FULL-LENGTH CDNA OF DENGUE TYPE-4 VIRUS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DENGUE VIRUS; INFECTIOUS TRANSCRIPTS; VIRUS GENETICS ID RECOMBINANT VACCINIA VIRUS; YELLOW-FEVER VIRUS; STRUCTURAL PROTEINS; NONSTRUCTURAL PROTEIN-NS1; VIRAL-DNA; INVITRO; SEQUENCE; POLYPROTEIN; EXPRESSION; CLEAVAGE AB Dengue virus is an enveloped positive-strand RNA virus with a genome almost-equal-to 11 kilobases in length. The four serotypes of dengue virus are currently the most important members of the flavivirus family in terms of geographical distribution and the incidence of infection in humans. In this communication we describe successful cloning of a stable full-length cDNA copy of dengue type 4 virus that can be used as the template for in vitro transcription of infectious RNA. Evidence is presented that dengue virus recovered from permissive cells transfected with the in vitro RNA transcripts retained a mutation that was engineered into full-length cDNA. The properties of the virus produced by cells transfected with infectious RNA transcripts of dengue cDNA resembled those of the virus from which the cDNA clone was derived. The dengue virus recombinant DNA system should prove helpful in gaining a better understanding of the molecular biology of dengue viruses and should facilitate the development of a safe and effective live vaccine for use in humans. RP LAI, CJ (reprint author), NIAID,INFECT DIS LAB,MOLEC VIRAL BIOL SECT,BETHESDA,MD 20892, USA. NR 27 TC 174 Z9 195 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN PY 1991 VL 88 IS 12 BP 5139 EP 5143 DI 10.1073/pnas.88.12.5139 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FR448 UT WOS:A1991FR44800016 PM 2052593 ER PT J AU LEE, B AF LEE, B TI ISOENTHALPIC AND ISOENTROPIC TEMPERATURES AND THE THERMODYNAMICS OF PROTEIN DENATURATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HYDROPHOBICITY; PROTEIN STABILITY ID CAVITY SURFACE-AREA; AMINO-ACID-RESIDUES; HYDROPHOBIC INTERACTION; HEAT-CAPACITY; GLOBULAR-PROTEINS; WATER; STABILITY; HYDROCARBONS; DEPENDENCE; SOLUBILITY AB The standard enthalpy or entropy change upon transfer of a small nonpolar molecule from a nonaqueous phase into water at a given temperature is generally different for different solute species. However, if the heat capacity change is independent of temperature, there exists a temperature at which the enthalpy or the entropy change becomes the same for all solute species within a given class. Similarly, the enthalpy or the entropy change of protein denaturation, when extrapolated to high temperature assuming a temperature-independent heat capacity change, shows a temperature at which its value becomes the same for many different globular proteins on a per weight basis. It is shown that the existence of these temperatures can be explained from a common formalism based on a linear relationship between the thermodynamic quantity and a temperature-independent molecular property that characterizes the solute or the protein. For the small nonpolar molecule transfer processes, this property is the surface area or the number of groups that are brought in contact with water. For protein denaturation, it is suggested that this property measures the polar/nonpolar mix of the internal interaction within the protein interior. Under a certain set of assumptions, this model leads to the conclusion that the nonpolar and the polar groups of the protein contribute roughly equally to the stability of the folded state of the molecule and that the solvent-accessible surface area of the denatured form of a protein is no more than about two-thirds that of the fully extended form. RP LEE, B (reprint author), NIH,BLDG 12A,ROOM 2007,BETHESDA,MD 20892, USA. RI Lee, Byungkook/E-4564-2011 OI Lee, Byungkook/0000-0002-3339-4582 NR 34 TC 108 Z9 108 U1 2 U2 8 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 JUN PY 1991 VL 88 IS 12 BP 5154 EP 5158 DI 10.1073/pnas.88.12.5154 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FR448 UT WOS:A1991FR44800019 PM 2052594 ER PT J AU MIKI, T FLEMING, TP CRESCENZI, M MOLLOY, CJ BLAM, SB REYNOLDS, SH AARONSON, SA AF MIKI, T FLEMING, TP CRESCENZI, M MOLLOY, CJ BLAM, SB REYNOLDS, SH AARONSON, SA TI DEVELOPMENT OF A HIGHLY EFFICIENT EXPRESSION CDNA CLONING SYSTEM - APPLICATION TO ONCOGENE ISOLATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MOUSE HEPATOMA; STABLE EXPRESSION; PLASMID RESCUE; B-RAF GENE; INVIVO ACTIVATION ID RECEPTOR CDNA; RAF; SEQUENCES; GENES; CELLS; DNA; ACTIVATION; INSERTS; GROWTH; MEMBER AB We developed an expression cDNA cloning system capable of generating high-complexity libraries with unidirectionally inserted cDNA fragments and allowing efficient plasmid rescue. As an application of this system, a cDNA library was constructed from an NIH 3T3 transformant induced by mouse hepatocellular carcinoma DNA. Transfection of NIH 3T3 cells by the library DNA led to the detection of several transformed foci from which identical plasmids with transforming ability could be rescued. Structure and sequence analysis of the cDNA clones revealed that the oncogene was created by recombinational events involving an unknown gene and the mouse homologue of the B-raf protooncogene. Detection of the same genetic rearrangement in independent primary transformants implied that generation of the oncogene occurred within the tumor rather than during DNA transfection or cDNA library construction. The high frequency at which clones were identified and the large sizes of some of the transforming cDNA inserts isolated suggest wide applicability of this mammalian expression cloning system for isolating cDNAs of biologic interest. C1 NCI,CELLULAR & MOLEC BIOL LAB,BLDG 37,ROOM 1E24,BETHESDA,MD 20892. NIEHS,BIOL RISK ASSESSMENT PROGRAM,RES TRIANGLE PK,NC 27709. RI Molloy, Christopher/A-6821-2013 OI Molloy, Christopher/0000-0003-2964-6166 NR 28 TC 176 Z9 177 U1 0 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 JUN PY 1991 VL 88 IS 12 BP 5167 EP 5171 DI 10.1073/pnas.88.12.5167 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FR448 UT WOS:A1991FR44800022 PM 2052597 ER PT J AU MUSTER, T SUBBARAO, EK ENAMI, M MURPHY, BR PALESE, P AF MUSTER, T SUBBARAO, EK ENAMI, M MURPHY, BR PALESE, P TI AN INFLUENZA-A VIRUS CONTAINING INFLUENZA-B VIRUS 5' AND 3' NONCODING REGIONS ON THE NEURAMINIDASE GENE IS ATTENUATED IN MICE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GENOME; CELLS; INFECTION; RNAS; RECOMBINANTS; POLYMERASE; POLIOVIRUS; MUTATIONS; VIRULENCE; SEQUENCE AB Influenza A and B viruses have not been shown to form reassortants. It had been assumed that the lack of genotypic mixing between influenza virus types reflected differences in polymerase and packaging specificity. In this study, we show that an influenza A virus polymerase transcribes and replicates a chloramphenicol acetyltransferase (CAT) gene flanked by the nontranslated sequences of an influenza B virus gene. Although the transcription level of this CAT gene was several times lower than that of a CAT gene flanked by the homologous nontranslated sequences of an influenza A virus, we proceeded to construct a chimeric type A/B influenza virus. Using recombinant DNA techniques, a chimeric neuraminidase gene was introduced into the genome of influenza A/WSN/33 virus. The hybrid influenza A/B virus gene contained the coding region of the A/WSN neuraminidase and the 3'and 5' nontranslated sequences of the nonstructural gene of influenza B/Lee virus. The resulting chimeric virus formed plaques in Madin-Darby bovine kidney cells but replicated more slowly and achieved lower titers than wild-type influenza A/WSN/33 virus. The chimeric virus was attenuated for mice as indicated by a 400-fold increase in its LD50. Interestingly, the virus was greatly restricted in replication in the upper respiratory tract and partially restricted in the lungs. Animals infected with the transfectant virus were highly resistant to influenza virus challenge. It appears that this chimeric virus has many of the properties desirable for a live attenuated virus vaccine. C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. RP MUSTER, T (reprint author), CUNY MT SINAI SCH MED,DEPT MICROBIOL,1 GUSTAVE L LEVY PL,NEW YORK,NY 10029, USA. OI Palese, Peter/0000-0002-0337-5823 FU NIAID NIH HHS [AI-18998, AI-11823, AI-24460] NR 25 TC 84 Z9 87 U1 0 U2 4 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 JUN PY 1991 VL 88 IS 12 BP 5177 EP 5181 DI 10.1073/pnas.88.12.5177 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FR448 UT WOS:A1991FR44800024 PM 2052599 ER PT J AU YLAHERTTUALA, S LIPTON, BA ROSENFELD, ME SARKIOJA, T YOSHIMURA, T LEONARD, EJ WITZTUM, JL STEINBERG, D AF YLAHERTTUALA, S LIPTON, BA ROSENFELD, ME SARKIOJA, T YOSHIMURA, T LEONARD, EJ WITZTUM, JL STEINBERG, D TI EXPRESSION OF MONOCYTE CHEMOATTRACTANT PROTEIN-1 IN MACROPHAGE-RICH AREAS OF HUMAN AND RABBIT ATHEROSCLEROTIC LESIONS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE INSITU HYBRIDIZATION; IMMUNOCYTOCHEMISTRY; RNA PROBES; MESSENGER RNA; FOAM CELLS ID LOW-DENSITY-LIPOPROTEIN; SMOOTH-MUSCLE CELLS; HUMAN ENDOTHELIAL-CELLS; IMMUNOCYTOCHEMICAL ANALYSIS; OXIDATIVE MODIFICATION; MONOCLONAL-ANTIBODIES; HUMAN-FIBROBLASTS; NONHUMAN PRIMATE; BLOOD MONOCYTES; GENE-JE AB The recruitment of monocyte-macrophages into the artery wall is one of the earliest events in the pathogenesis of atherosclerosis. Monocyte chemoattractant protein 1 (MCP-1) is a potent monocyte chemoattractant secreted by many cells in vitro, including vascular smooth muscle and endothelial cells. To test whether it is expressed in the artery in vivo, we used Northern blot analysis, in situ hybridization, and immunocytochemistry to study the expression of MCP-1 in normal and atherosclerotic human and rabbit arteries. Northern blot analysis showed that MCP-1 mRNA could be isolated from rabbit atherosclerotic lesions but not from the intima media of normal animals. Furthermore, MCP-1 mRNA was extracted from macrophage-derived foam cells isolated from arterial lesions of ballooned cholesterol-fed rabbits, whereas alveolar macrophages isolated simultaneously from the same rabbits did not express MCP-1 mRNA. MCP-1 mRNA was detected by in situ hybridization in macrophage-rich regions of both human and rabbit atherosclerotic lesions. No MCP-1 mRNA was found in sublesional medial smooth muscle cells or in normal arteries. By using immunocytochemistry, MCP-1 protein was demonstrated in human lesions, again only in macrophage-rich regions. Immunostaining of the serial sections with an antiserum against malondialdehyde-modified low density lipoprotein indicated the presence of oxidized low density lipoprotein and/or other oxidation-specific lipid-protein adducts in the same areas that contained macrophages and MCP-1. We conclude that (i) MCP-1 is strongly expressed in a small subset of cells in macrophage-rich regions of human and rabbit atherosclerotic lesions and (ii) MCP-1 may, therefore, play an important role in the ongoing recruitment of monocyte-macrophages into developing lesions in vivo. C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. UNIV OULU,DEPT FORENS MED,SF-90100 OULU 10,FINLAND. RP YLAHERTTUALA, S (reprint author), UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093, USA. NR 39 TC 725 Z9 742 U1 1 U2 14 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 JUN PY 1991 VL 88 IS 12 BP 5252 EP 5256 DI 10.1073/pnas.88.12.5252 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FR448 UT WOS:A1991FR44800039 PM 2052604 ER PT J AU TAKAHASHI, R HASHIMOTO, T XU, HJ HU, SX MATSUI, T MIKI, T BIGOMARSHALL, H AARONSON, SA BENEDICT, WF AF TAKAHASHI, R HASHIMOTO, T XU, HJ HU, SX MATSUI, T MIKI, T BIGOMARSHALL, H AARONSON, SA BENEDICT, WF TI THE RETINOBLASTOMA GENE FUNCTIONS AS A GROWTH AND TUMOR SUPPRESSOR IN HUMAN BLADDER-CARCINOMA CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ANTIONCOGENE; GENE TRANSFECTION; TUMORIGENICITY; GROWTH REGULATION ID SUSCEPTIBILITY GENE; RB GENE; HUMAN CANCER; PRODUCT; DNA; EXPRESSION; CYCLE; PHOSPHORYLATION; TUMORIGENICITY; INACTIVATION AB The product of the human retinoblastoma gene (RB) is a nuclear phosphoprotein that is thought to function as a tumor suppressor. Mutations of RB frequently occur in human bladder carcinoma. To investigate the significance of the functional loss of this gene in bladder cancer, an RB expression plasmid (pBARB) under control of the human beta-actin promoter was transfected into the bladder carcinoma cell line HTB9, which lacks RB expression. Marker-selected transfectants that expressed RB protein were identified by immunoblotting and immunohistochemical staining. In selected clones, stable RB expression has persisted over 1 yr under standard culture conditions with 10% serum. However, RB expression caused major alterations of HTB9 growth properties both in vitro and in vivo. RB+ transfectants lacked the ability to form colonies in semi-solid medium, and their growth rate was significantly decreased in 3% serum. In addition, the tumorigenicity of these transfectants was markedly decreased. Tumors that formed in nude mice were much smaller and had a longer latency period but were indistinguishable microscopically from those produced by parental cells. Slower growing tumors were RB+, as measured by nuclear staining of their RB protein and by a normal RB protein pattern on immunoblots. These findings support the concept that the RB gene acts as both a growth and tumor suppressor in bladder cancer cells. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. KOBE UNIV,SCH MED,DEPT MED,CHUO KU,KOBE 650,JAPAN. RP TAKAHASHI, R (reprint author), CTR BIOTECHNOL,4000 RES FOREST DR,THE WOODLANDS,TX 77381, USA. RI Matsui, Toshimitsu/E-8065-2010 FU NEI NIH HHS [EY06195, EY02715] NR 23 TC 187 Z9 187 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 JUN PY 1991 VL 88 IS 12 BP 5257 EP 5261 DI 10.1073/pnas.88.12.5257 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FR448 UT WOS:A1991FR44800040 PM 2052605 ER PT J AU GAIDANO, G BALLERINI, P GONG, JZ INGHIRAMI, G NERI, A NEWCOMB, EW MAGRATH, IT KNOWLES, DM DALLAFAVERA, R AF GAIDANO, G BALLERINI, P GONG, JZ INGHIRAMI, G NERI, A NEWCOMB, EW MAGRATH, IT KNOWLES, DM DALLAFAVERA, R TI P53 MUTATIONS IN HUMAN LYMPHOID MALIGNANCIES - ASSOCIATION WITH BURKITT-LYMPHOMA AND CHRONIC LYMPHOCYTIC-LEUKEMIA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TUMOR SUPPRESSOR GENES ID POINT MUTATIONS; LUNG-CANCER; CELL-LINES; GENE; ONCOGENE; ABNORMALITIES; INACTIVATION; SUPPRESSOR; EXPRESSION; DELETIONS AB We have investigated the frequency of p53 mutations in B- and T-cell human lymphoid malignancies, including acute lymphoblastic leukemia, the major subtypes of non-Hodgkin lymphoma, and chronic lymphocytic leukemia. p53 exons 5-9 were studied by using genomic DNA from 197 primary tumors and 27 cell lines by single-strand conformation polymorphism analysis and by direct sequencing of PCR-amplified fragments. Mutations were found associated with (i) Burkitt lymphoma (9/27 biopsies; 17/27 cell lines) and its leukemic counterpart L3-type B-cell acute lymphoblastic leukemia (5/9), both of which also carry activated c-myc oncogenes, and (ii) B-cell chronic lymphocytic leukemia (6/40) and, in particular, its stage of progression known as Richter's transformation (3/7). Mutations were not found at any significant frequency in other types of non-Hodgkin lymphoma or acute lymphoblastic leukemia. In many cases, only the mutated allele was detectable, implying loss of the normal allele. These results suggest that (i) significant differences in the frequency of p53 mutations are present among subtypes of neoplasms derived from the same tissue; (ii) p53 may play a role in tumor progression in B-cell chronic lymphocytic leukemia; (iii) the presence of both p53 loss/inactivation and c-myc oncogene activation may be important in the pathogenesis of Burkitt lymphoma and its leukemic form L3-type B-cell acute lymphoblastic leukemia. C1 COLUMBIA UNIV COLL PHYS & SURG,CTR CANC,NEW YORK,NY 10032. NYU,SCH MED,DEPT PATHOL,NEW YORK,NY 10032. NYU,SCH MED,CTR CANC,NEW YORK,NY 10032. OSPED MAGGIORE,CTR MALATTIE SANGUE G MARCORA,I-20122 MILANI,ITALY. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. RP GAIDANO, G (reprint author), COLUMBIA UNIV COLL PHYS & SURG,DEPT PATHOL,NEW YORK,NY 10032, USA. OI neri, antonino/0000-0001-9047-5912 FU NCI NIH HHS [CA40236, CA44029]; NEI NIH HHS [EY06337] NR 33 TC 819 Z9 828 U1 0 U2 9 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 JUN PY 1991 VL 88 IS 12 BP 5413 EP 5417 DI 10.1073/pnas.88.12.5413 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FR448 UT WOS:A1991FR44800072 PM 2052620 ER PT J AU PARK, DJ RHO, HW RHEE, SG AF PARK, DJ RHO, HW RHEE, SG TI CD3 STIMULATION CAUSES PHOSPHORYLATION OF PHOSPHOLIPASE C-GAMMA-1 ON SERINE AND TYROSINE RESIDUES IN A HUMAN T-CELL LINE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE INOSITOL PHOSPHATE; TYROSINE KINASE ID T3-ANTIGEN RECEPTOR COMPLEX; ANTIGEN RECEPTOR; C-GAMMA; SIGNAL TRANSDUCTION; PROTEIN-KINASE; BOVINE BRAIN; ACTIVATION; ASSOCIATION; CALCIUM AB The human T-cell line Jurkat was found to contain at least two immunologically distinct isoforms of inositol phospholipid-specific phospholipase C (PLC), PLC-beta-1 and PLC-gamma-1. Treatment of Jurkat cells with antibody to CD3 led to phosphorylation of PLC-gamma-1 but not of PLC-beta-1. The phosphorylation of PLC-gamma-1 occurred rapidly and transiently on both serine and tyrosine residues; tyrosine phosphorylation reached a maximum level less than 1 min after stimulation and decreased rapidly, both in the presence and in the absence of orthovanadate. Two-dimensional phosphopeptide map analysis revealed that the major sites of tyrosine and serine phosphorylation in PLC-gamma-1 from activated Jurkat cells are the same as those in PLC-gamma-1 from cells treated with peptide growth factors such as epidermal growth factor and platelet-derived growth factor. Previously, it has been shown that multiple phosphorylation of PLC-gamma-1 by the growth factor receptor tyrosine kinases leads to activation of PLC-gamma-1. Thus, the current data suggest that inositol phospholipid hydrolysis triggered by the T-cell antigen receptor-CD3 complex is due, at least in part, to activation of PLC-gamma-1 and that the mechanism by which this activation is achieved involves phosphorylation of multiple tyrosine residues on PLC-gamma-1 by a nonreceptor tyrosine kinase coupled to the T-cell antigen receptor-CD3 complex. C1 NHLBI, BIOCHEM LAB,SIGNAL TRANSDUCT SECT,BLDG 3,ROOM 122, BETHESDA, MD 20892 USA. RI Park, Do-Joon/J-2736-2012 NR 31 TC 292 Z9 293 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN PY 1991 VL 88 IS 12 BP 5453 EP 5456 DI 10.1073/pnas.88.12.5453 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FR448 UT WOS:A1991FR44800080 PM 1828897 ER PT J AU BENKELFAT, C MEFFORD, IN MASTERS, CF NORDAHL, TE KING, AC COHEN, RM MURPHY, DL AF BENKELFAT, C MEFFORD, IN MASTERS, CF NORDAHL, TE KING, AC COHEN, RM MURPHY, DL TI PLASMA-CATECHOLAMINES AND THEIR METABOLITES IN OBSESSIVE-COMPULSIVE DISORDER SO PSYCHIATRY RESEARCH LA English DT Article DE EPINEPHRINE; NOREPINEPHRINE; HOMOVANILLIC ACID; 3-METHOXY-4-HYDROXYPHENYLGLYCOL; CORTISOL; SYMPATHOADRENAL ACTIVITY ID PERFORMANCE LIQUID-CHROMATOGRAPHY; CLOMIPRAMINE TREATMENT; ELECTROCHEMICAL DETECTION; M-CHLOROPHENYLPIPERAZINE; HOMOVANILLIC-ACID; NOREPINEPHRINE; RESPONSIVITY; DEPRESSION; DOPAMINE; KINETICS AB Plasma catecholamines and their metabolites were sampled in 13 medication-free patients with obsessive-compulsive disorder (OCD) and 29 normal controls. In addition to severe OCD symptoms, the patients had significantly higher anxiety, tension, and resting pulse rates than the controls. Nonetheless, mean plasma concentrations of norepinephrine (NE) and epinephrine (E), the catecholamine metabolites 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA), and the stress-related hormone cortisol did not differ between OCD patients and normal controls. When the patients and control populations were combined and average plasma NE and E levels calculated over 35 min, subjects with a higher mean NE output (> 1.1 pm/ml) had higher Profile of Mood States depression scores than subjects with a low NE output (< 1.1 pm/ml). Altogether, these results indicate that elevated plasma catecholamine measures are not likely to be associated with the pathophysiology of OCD. C1 NIMH,EXPTL THERAPEUT BRANCH,CLIN NEUROCHEM UNIT,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. UNIV CALIF DAVIS,DEPT PSYCHIAT,DAVIS,CA 95616. NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. NIMH,CEREBRAL METAB LAB,CLIN BRAIN IMAGING SECT,BETHESDA,MD 20892. RP BENKELFAT, C (reprint author), MCGILL UNIV,DEPT PSYCHIAT,NEUROBIOL PSYCHIAT UNIT,RES & TRAINING BLDG,RM 208,1033 PINE AVE,MONTREAL H3A 1A1,QUEBEC,CANADA. RI Nordahl, Thomas/J-7643-2013 OI Nordahl, Thomas/0000-0002-8627-0356 NR 38 TC 26 Z9 26 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD JUN PY 1991 VL 37 IS 3 BP 321 EP 331 DI 10.1016/0165-1781(91)90067-Y PG 11 WC Psychiatry SC Psychiatry GA FX278 UT WOS:A1991FX27800010 PM 1891512 ER PT J AU PARASURAMAN, R GIAMBRA, L AF PARASURAMAN, R GIAMBRA, L TI SKILL DEVELOPMENT IN VIGILANCE - EFFECTS OF EVENT RATE AND AGE SO PSYCHOLOGY AND AGING LA English DT Article ID SUSTAINED-ATTENTION; SIGNAL-DETECTION; PERFORMANCE; TIME; DECREMENT; TASK C1 NIA,GERONTOL RES CTR,PERSONAL & COGNIT LAB,BALTIMORE,MD 21224. RP PARASURAMAN, R (reprint author), CATHOLIC UNIV AMER,DEPT PSYCHOL,WASHINGTON,DC 20064, USA. FU NIMHD NIH HHS [263-MD-712174] NR 49 TC 63 Z9 64 U1 1 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0882-7974 J9 PSYCHOL AGING JI Psychol. Aging PD JUN PY 1991 VL 6 IS 2 BP 155 EP 169 PG 15 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA FQ045 UT WOS:A1991FQ04500001 PM 1863385 ER PT J AU WOLFF, SD CHESNICK, S FRANK, JA LIM, KO BALABAN, RS AF WOLFF, SD CHESNICK, S FRANK, JA LIM, KO BALABAN, RS TI MAGNETIZATION TRANSFER CONTRAST - MR-IMAGING OF THE KNEE SO RADIOLOGY LA English DT Article DE KNEE, MR STUDIES; MAGNETIC RESONANCE (MR), CONTRAST ENHANCEMENT; MAGNETIC RESONANCE (MR), MAGNETIZATION TRANSFER CONTRAST; MAGNETIC RESONANCE (MR), TECHNOLOGY; MAGNETIC RESONANCE (MR), TISSUE CHARACTERIZATION ID MENISCI AB The use of magnetization transfer contrast (MTC) in magnetic resonance imaging of the human knee was evaluated in this study. MTC is generated by irradiating the macromolecular protons in tissue with a low power off-resonance radio-frequency field. This results in a decrease in water proton signal intensity where a tight magnetic coupling between water and macromolecules exists. With this approach, the authors have demonstrated that MTC can improve contrast in standard single-section, gradient-recalled-echo images of the knee with regard to fat-muscle and cartilage-synovial fluid comparisons. The effect of changes in repetition time, echo time, and flip angle were also quantitatively evaluated. More important, MTC was shown to generate useful cartilage-synovial fluid contrast on high-resolution three-dimensional images, in which contrast is difficult to generate. This approach may not only provide better structural information about the knee, but may also provide noninvasive insight into the structure and biochemical composition of cartilage in vivo. C1 NHLBI,CARDIAC ENERGET LAB,BLDG 1,RM B3-07,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,DEPT RADIOL,BALTIMORE,MD 21218. NIH,CTR HLTH CLIN,DEPT RADIOL,BETHESDA,MD 20892. STANFORD UNIV,DEPT PSYCHIAT & BEHAV SCI,STANFORD,CA 94305. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 20 TC 144 Z9 146 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 1991 VL 179 IS 3 BP 623 EP 628 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA FM910 UT WOS:A1991FM91000008 PM 2027963 ER PT J AU HRICAK, H RUBINSTEIN, LV GHERMAN, GM KARSTAEDT, N AF HRICAK, H RUBINSTEIN, LV GHERMAN, GM KARSTAEDT, N TI MR-IMAGING EVALUATION OF ENDOMETRIAL CARCINOMA - RESULTS OF AN NCI COOPERATIVE STUDY SO RADIOLOGY LA English DT Article DE UTERINE NEOPLASMS, MR-STUDIES; UTERINE NEOPLASMS, STAGING ID MYOMETRIAL INVASION AB A prospective study to assess the usefulness of magnetic resonance (MR) imaging in the evaluation of endometrial carcinoma was undertaken by five institutions under the auspices of the National Cancer Institute. Six different MR imagers were used, ranging in magnetic field strength from 0.15 T to 1.5 T. For each unit, appropriate T1- and T2-weighted sequences in the transverse plane and T2-weighted sequences in the sagittal plane were used. Initially, 107 patients were entered in the study, but only 88 fulfilled all the criteria and provide the basis for this study. The abnormality within the endometrical cavity was demonstrated with MR imaging in 81% of the patients. The overall accuracy with MR imaging for staging endometrial carcinoma was 85%. In the evaluation of depth of myometrial invasion for stage I disease, overall accuracy with MR imaging was 74%. The accuracy of MR imaging in assessing tumors confined to endometrium or tumor with superficial myometrial invasion was 89% and decreased to 54% in assessing deep myometrial invasion. The results of this prospective study performed by multiple examiners with vastly different equipment demonstrate the inherent value of MR imaging in the evaluation of this neoplasm. C1 NCI,DEPT HLTH & HUMAN SERV,BETHESDA,MD 20892. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT RADIOL,WINSTON SALEM,NC 27103. RP HRICAK, H (reprint author), UNIV CALIF SAN FRANCISCO,DEPT RADIOL,505 PARNASSUS,SAN FRANCISCO,CA 94143, USA. FU NCI NIH HHS [N0I-CM-42684] NR 12 TC 157 Z9 159 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 1991 VL 179 IS 3 BP 829 EP 832 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA FM910 UT WOS:A1991FM91000048 PM 2028000 ER PT J AU MILLER, DL CHOYKE, PL WALTHER, MM DOPPMAN, JL KRAGEL, PJ WEISS, GH LINEHAN, WM AF MILLER, DL CHOYKE, PL WALTHER, MM DOPPMAN, JL KRAGEL, PJ WEISS, GH LINEHAN, WM TI VONHIPPEL-LINDAU DISEASE - INADEQUACY OF ANGIOGRAPHY FOR IDENTIFICATION OF RENAL CANCERS SO RADIOLOGY LA English DT Article DE ANGIOGRAPHY; KIDNEY, CYSTS; KIDNEY, MR-STUDIES; KIDNEY, US-STUDIES; KIDNEY NEOPLASMS, ANGIOGRAPHY; VONHIPPEL-LINDAU DISEASE ID CELL CARCINOMA; MANAGEMENT; MANIFESTATIONS; ARTERIOGRAPHY; CYSTS AB Selective renal angiograms were retrospectively evaluated for the identification of renal cell cancers in patients with von Hippel-Lindau disease (VHL). Seven patients underwent angiography and surgery because of solid or complex renal masses identified at cross-sectional imaging. Nine kidneys underwent detailed examination by the surgeon and by a pathologist. There were 31 renal cancers. Angiography had enabled identification of only five cancers (16%), and six others (19%) had been suspected. Cancers detected angiographically were larger than those not detected (P < .05). Solid tumors tended to appear less hypervascular than expected and occasionally had the angiographic appearance of atypical cysts. There were no false-positive angiograms. Angiography revealed only one cancer not previously suspected and changed the surgeon's approach for only one kidney (11%). The sensitivity and specificity of angiography were 35% and 100%, respectively. In these patients, selective renal angiography is not helpful for the detection or exclusion of cancer in a kidney. It does have a limited role for vascular mapping prior to partial nephrectomy or tumor enucleation. C1 NCI,DIV CANC TREATMENT,SURG BRANCH,UROL ONCOL SECT,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT RADIOL,WASHINGTON,DC 20007. RP MILLER, DL (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BLDG 10,BETHESDA,MD 20892, USA. NR 25 TC 15 Z9 17 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 1991 VL 179 IS 3 BP 833 EP 836 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA FM910 UT WOS:A1991FM91000049 PM 2028001 ER PT J AU ROGAN, WJ BLANTON, PJ PORTIER, CJ STALLARD, E AF ROGAN, WJ BLANTON, PJ PORTIER, CJ STALLARD, E TI SHOULD THE PRESENCE OF CARCINOGENS IN BREAST-MILK DISCOURAGE BREAST-FEEDING SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article ID DICHLORODIPHENYL DICHLOROETHENE DDE; POLYCHLORINATED-BIPHENYLS PCBS; N-NITROSODIMETHYLAMINE; LIVER-TUMORS; RISK; LACTATION; DEATH; INFANTS; MODELS; CANCER C1 COMP SCI CORP,RES TRIANGLE PK,NC 27709. NIEHS,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709. DUKE UNIV,CTR DEMOG STUDIES,DURHAM,NC 27706. RP ROGAN, WJ (reprint author), NIEHS,EPIDEMIOL BRANCH,MAIL DROP A3-05,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Portier, Christopher/A-3160-2010; Rogan, Walter/I-6034-2012 OI Portier, Christopher/0000-0002-0954-0279; Rogan, Walter/0000-0002-9302-0160 FU NIA NIH HHS [5-RO1-AG-01159] NR 36 TC 32 Z9 34 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 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD JUN PY 1991 VL 13 IS 3 BP 228 EP 240 DI 10.1016/0273-2300(91)90065-4 PG 13 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA FR383 UT WOS:A1991FR38300002 PM 1947235 ER PT J AU MANOLIOS, N GECZY, C SCHRIEBER, L AF MANOLIOS, N GECZY, C SCHRIEBER, L TI LYMPHOCYTE MIGRATION IN HEALTH AND INFLAMMATORY RHEUMATIC DISEASE SO SEMINARS IN ARTHRITIS AND RHEUMATISM LA English DT Article DE LYMPHOCYTE MIGRATION; RECIRCULATION; HOMING; HIGH ENDOTHELIAL; VENULES; INFLAMMATORY RHEUMATIC DISEASE ID SYSTEMIC LUPUS-ERYTHEMATOSUS; ENDOTHELIAL-CELL RECOGNITION; HUMAN GAMMA-INTERFERON; TUMOR NECROSIS FACTOR; NODE HOMING RECEPTOR; ACTIVATED T-CELLS; JAPAN 305 H2N2; VASCULAR ENDOTHELIUM; SYNOVIAL-MEMBRANE; NZB MICE C1 SYDNEY UNIV,ROYAL N SHORE HOSP,DEPT RHEUMATOL,ST LEONARDS,NSW 2065,AUSTRALIA. NATL INST CHILD HLTH & DEV,CELL BIOL & CELL METAB BRANCH,BETHESDA,MD. HEART RES INST,CAMPERDOWN,AUSTRALIA. NR 98 TC 14 Z9 14 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0049-0172 J9 SEMIN ARTHRITIS RHEU JI Semin. Arthritis Rheum. PD JUN PY 1991 VL 20 IS 6 BP 339 EP 352 DI 10.1016/0049-0172(91)90010-W PG 14 WC Rheumatology SC Rheumatology GA FR689 UT WOS:A1991FR68900001 ER PT J AU BOYKIN, FF AF BOYKIN, FF TI THE AIDS CRISIS AND GAY MALE SURVIVOR GUILT SO SMITH COLLEGE STUDIES IN SOCIAL WORK LA English DT Article ID UNITED-STATES; GRIEF AB Since 1981, Acquired Immunodeficiency Syndrome (AIDS) has affected the lives of many Americans, particularly the lives of gay males. There is little research on the effects of grief and bereavement this community continues to experience. Therefore, an investigation was undertaken to find whether survivor guilt was evident in gay males in a large metropolitan community. Fifteen gay men were interviewed on their experiences of grief and survivor guilt and 77 questionnaires containing a subset of interview questions were completed. Results indicate that a modest amount of survivor guilt is experienced in the gay community; those with more experience of HIV or AIDS related illnesses and deaths had less survivor guilt than those who had experienced fewer illnesses and deaths. Gay men who are involved with gay/AIDS organizations have a significant reduction in survivor guilt feelings. The majority of gay men think about persons suffering or dying from AIDS a great deal of the time; thus therapists should explore the history of AIDS loss in gay male clients. The denial that some gay men use in relation to their feelings about those who have died from AIDS should be examined carefully. Furthermore, the need for gay bereavement groups and resocialization groups will continue to expand. RP BOYKIN, FF (reprint author), NIH,INFECT DIS UNIT,BETHESDA,MD 20892, USA. NR 28 TC 4 Z9 4 U1 1 U2 2 PU SMITH COLLEGE SCH SOC WORK PI NORTHAMPTON PA LILLY HALL, NORTHAMPTON, MA 01063 SN 0037-7317 J9 SMITH COLL STUD SOC JI Smith Coll. Stud. Soc. Work PD JUN PY 1991 VL 61 IS 3 BP 247 EP 259 PG 13 WC Social Work SC Social Work GA GZ761 UT WOS:A1991GZ76100004 ER PT J AU SHEPPARD, BC NORTON, JA AF SHEPPARD, BC NORTON, JA TI TUMOR-NECROSIS-FACTOR AND INTERLEUKIN-1 PROTECTION AGAINST THE LETHAL EFFECTS OF TUMOR-NECROSIS-FACTOR SO SURGERY LA English DT Article ID LISTERIA-MONOCYTOGENES INFECTION; MANGANOUS SUPEROXIDE-DISMUTASE; FACTOR-ALPHA; BACTERIAL-INFECTION; RECOMBINANT INTERLEUKIN-1-ALPHA; ANTIBACTERIAL RESISTANCE; ENDOTOXIN TOLERANCE; HOST-RESISTANCE; FACTOR TNF; MICE AB Based on the hypothesis that tumor necrosis factor (TNF) causes the lethality of gram-negative sepsis and previous work of tolerance to the lethal effects of TNF induced by repetitive exposure to sublethal intraperitoneal doses of human recombinant (r) TNF, we studied the protective role of a single sublethal intravenous dose of either rTNF (100-mu-g/kg) or recombinant interleukin-1 (rIL-1; 10(5) units/kg) or both before a subsequent lethal intravenous dose of rTNF (800 to 1000-mu-g/kg) in C3H/HEN mice. Mice were treated with a single intravenous dose of saline, rTNF, rIL-1 or both cytokines and challenged within 2 hours to 10 days with a lethal dose of rTNF. Mice treated with rTNF showed significant protection against the lethal effects of TNF when the treatment dose was given only 2 hours before the lethal dose, but maximal protection required a 24-hour interval and lasted as long as 8 days. The treatment dose of rTNF was toxic, and it resulted in occasional treatment deaths. Mice treated with rIL-1 showed maximal protection when treatment was given only 2 hours before challenge and protection lasted for 8 days. No toxicity was apparent secondary to IL-1 treatment. The combination of rIL-1 and rTNF was not as effective as either cytokine alone. The results suggest that rTNF or rIL-1 may be clinically useful in the prevention and treatment of sepsis lethality by the induction of tolerance to the lethal effects of TNF. The more promising cytokine appears to be rIL-1 because it has less toxicity and more rapid induction of full therapeutic effectiveness. C1 NCI,SURG BRANCH,SURG METAB SECT,BLDG 10,ROOM 2B07,BETHESDA,MD 20892. NR 43 TC 22 Z9 22 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD JUN PY 1991 VL 109 IS 6 BP 698 EP 705 PG 8 WC Surgery SC Surgery GA FQ372 UT WOS:A1991FQ37200003 PM 2042087 ER PT J AU CHURCHILL, L BOURDELAIS, A AUSTIN, MC LOLAIT, SJ MAHAN, LC OCARROLL, AM KALIVAS, PW AF CHURCHILL, L BOURDELAIS, A AUSTIN, MC LOLAIT, SJ MAHAN, LC OCARROLL, AM KALIVAS, PW TI GABA-A RECEPTORS CONTAINING ALPHA-1 AND BETA-2 SUBUNITS ARE MAINLY LOCALIZED ON NEURONS IN THE VENTRAL PALLIDUM SO SYNAPSE LA English DT Article DE GABA; RECEPTOR AUTORADIOGRAPHY; INSITU HYBRIDIZATION; GLUTAMIC ACID DECARBOXYLASE; NUCLEUS ACCUMBENS; VENTRAL PALLIDUM ID GAMMA-AMINOBUTYRIC-ACID; MESENCEPHALIC LOCOMOTOR REGION; MESOLIMBIC DOPAMINE SYSTEM; RAT SUBSTANTIA NIGRA; NUCLEUS ACCUMBENS; QUINOLINIC ACID; GLOBUS PALLIDUS; BASAL GANGLIA; GLUTAMATE-DECARBOXYLASE; NEUROTENSIN RECEPTORS AB The gamma-aminobutyric acid (GABA) projection from the nucleus accumbens to the ventral pallidum (VP) is important in the regulation of locomotion. Thus, stimulation and inhibition of GABA(A) receptors in the VP can alter locomotor activity. To determine whether the GABA(A) receptors are located presynaptically on accumbens efferents to the VP or postsynaptically on neurons intrinsic to the VP two experiments were performed. In the first, quinolinic acid lesions of the nucleus accumbens did not alter [H-3]muscimol binding in the VP, while lesions in the VP significantly reduced (60-80%) binding as measured by light microscopic receptor autoradiography. In the second experiment, in situ hybridization with oligonucleotide probes for mRNAs of the alpha-1 and beta-2 subunits of the GABA(A) receptor was examined in the nucleus accumbens and VP. No mRNA for either subunit was observed in the nucleus accumbens, although many positively labeled neurons were present within the VP. By contrast, a moderate to high density of cells in both the nucleus accumbens and VP contained mRNA for glutamic acid decarboxylse. These data argue that the majority of GABA(A) receptors in the VP are not located presynaptically on axonal terminals originating from neurons in the nucleus accumbens. C1 NIMH, BETHESDA, MD 20892 USA. RP WASHINGTON STATE UNIV, DEPT VET & COMPARAT ANAT PHARMACOL & PHYSIOL, PULLMAN, WA 99164 USA. FU NIDA NIH HHS [DA-03906]; NIMH NIH HHS [MH-40817] NR 72 TC 27 Z9 27 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0887-4476 EI 1098-2396 J9 SYNAPSE JI Synapse PD JUN PY 1991 VL 8 IS 2 BP 75 EP 85 DI 10.1002/syn.890080202 PG 11 WC Neurosciences SC Neurosciences & Neurology GA FN214 UT WOS:A1991FN21400001 PM 1652796 ER PT J AU ROTHMAN, RB BYKOV, V MAHBOUBI, A LONG, JB JIANG, Q PORRECA, F DECOSTA, BR JACOBSON, AE RICE, KC HOLADAY, JW AF ROTHMAN, RB BYKOV, V MAHBOUBI, A LONG, JB JIANG, Q PORRECA, F DECOSTA, BR JACOBSON, AE RICE, KC HOLADAY, JW TI INTERACTION OF BETA-FUNALTREXAMINE WITH [H-3] CYCLOFOXY BINDING IN RAT-BRAIN - FURTHER EVIDENCE THAT BETA-FNA ALKYLATES THE OPIOID RECEPTOR COMPLEX SO SYNAPSE LA English DT Article DE BETA-FNA; OPIOID RECEPTORS; ALKYLATING AGENTS; [H-3][D-ALA2,D-LEU5] ENKEPHALIN; CYCLOFOXY ID POSITRON EMISSION TOMOGRAPHY; SITE INTERACTIONS INVITRO; 2-SITE ALLOSTERIC MODEL; KAPPA-OPIATE RECEPTOR; MU-RECOGNITION SITE; GUINEA-PIG BRAIN; DELTA-RECEPTOR; ENANTIOSPECIFIC ACYLATION; FENTANYL ISOTHIOCYANATE; LEUCINE-H-3 ENKEPHALIN AB beta-Funaltrexamine (beta-FNA) is an alkylating derivative of naltrexone. In addition to acting as an irreversible inhibitor of mu-receptor-mediated physiological effects, intracerebroventricular (i.c.v.) administration of beta-FNA to rat attenuates the ability of selective delta receptor antagonists and naloxone to reverse delta receptor-mediated effects. Moreover, recent work demonstrated that i.c.v. administration of beta-FNA alters the conformation of the opioid receptor complex, as inferred by a decrease in the Bmax of the lower affinity [H-3][D-ala2,D-leu5]enkephalin binding site. Consistent with the decreased potency of naloxone as an inhibitor of delta receptor mediated effects, beta-FNA doubled the naloxone IC50 for displacing [H-3][D-ala2,D-leu5]enkephalin from its lower affinity binding site. These data collectively support the hypothesis that the opioid receptor complex postulated to mediate mu-delta interactions in vivo is identical to the opioid receptor complex as defined by vitro ligand binding studies. A direct prediction of this hypothesis is that beta-FNA should increase the Kd of antagonists for the mu binding site (mu-cx) of the receptor complex. The data reported in this paper demonstrate that beta-FNA doubled the IC50 of the potent narcotic antagonist, 6-desoxy-6-beta-fluoronaltrexone (cycloFOXY) for displacing [H-3][D-ala2,D-leu5]enkephalin from its lower affinity binding site, and doubled the Kd of [H-3]cycloFOXY for its mu binding site, providing additional data that the mu binding site labeled by [H-3]cycloFOXY is the mu binding site of the opioid receptor complex. beta-FNA also altered the kappa binding site labeled by [H-3]cycloFOXY, and when administered intrathecally to mice, beta-FNA produced a longlasting antinociception in the acetic acid writhing test. C1 WALTER REED ARMY MED CTR,DIV MED NEUROSCI,NEUROPHARMACOL BRANCH,WASHINGTON,DC 20307. UNIV ARIZONA,COLL MED,DEPT PHARMACOL,TUCSON,AZ 85724. NIDDK,MED CHEM LAB,DRUG DESIGN & SYNTHESIS SECT,BETHESDA,MD 20892. MEDICIS CORP,NEW YORK,NY 10017. RP ROTHMAN, RB (reprint author), NIDDK,MED CHEM LAB,RECEPTOR STUDIES UNIT,BETHESDA,MD 20892, USA. NR 62 TC 26 Z9 26 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 0887-4476 J9 SYNAPSE JI Synapse PD JUN PY 1991 VL 8 IS 2 BP 86 EP 99 DI 10.1002/syn.890080203 PG 14 WC Neurosciences SC Neurosciences & Neurology GA FN214 UT WOS:A1991FN21400002 PM 1652797 ER PT J AU LEW, R VAUGHAN, R SIMANTOV, R WILSON, A KUHAR, MJ AF LEW, R VAUGHAN, R SIMANTOV, R WILSON, A KUHAR, MJ TI DOPAMINE TRANSPORTERS IN THE NUCLEUS-ACCUMBENS AND THE STRIATUM HAVE DIFFERENT APPARENT MOLECULAR-WEIGHTS SO SYNAPSE LA English DT Note ID RAT STRIATUM; COCAINE C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. RP LEW, R (reprint author), NIDA,ADDICT RES CTR,NEUROSCI BRANCH,BALTIMORE,MD 21224, USA. RI Wilson, Alan/A-1788-2011 NR 8 TC 46 Z9 46 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 0887-4476 J9 SYNAPSE JI Synapse PD JUN PY 1991 VL 8 IS 2 BP 152 EP 153 DI 10.1002/syn.890080209 PG 2 WC Neurosciences SC Neurosciences & Neurology GA FN214 UT WOS:A1991FN21400008 PM 1882335 ER PT J AU HONG, HL YANG, RSH BOORMAN, GA AF HONG, HL YANG, RSH BOORMAN, GA TI RESIDUAL DAMAGE TO HEMATOPOIETIC SYSTEM IN MICE EXPOSED TO A MIXTURE OF GROUNDWATER CONTAMINANTS SO TOXICOLOGY LETTERS LA English DT Article DE RESIDUAL MARROW EFFECT; GROUNDWATER CONTAMINANTS; MICE; HEMATOPOIESIS; IRRADIATION ID BONE-MARROW; CHEMICAL-MIXTURE; B6C3F1 MICE; INHALED BENZENE; CFU-C; TOXICOLOGY; CELLS; ERYTHROPOIESIS; INHIBITION; LEUKEMIA AB To assess the potential health effects of chemically contaminated groundwater, we initiated a toxicological program on a mixture of 25 frequently-detected groundwater contaminants derived from hazardous waste disposal sites. As part of this program, myelotoxicity studies were conducted. Bone marrow parameters were examined in mice exposed to 0, 1, 5 or 10% of a simulated chemical mixture stock solution of groundwater contaminants in drinking water for 108 days. Mice treated with 5 or 10% of chemical mixture stock solution for 108 days showed suppressed marrow granulocyte macrophage progenitors (CFU-GM); however, this suppression disappeared in 10 weeks following the cessation of treatment. The possible toxicological interaction of groundwater contaminants and radiation on hematopoiesis was investigated by using the number of bone marrow CFU-GM as an index. When mice were exposed to 200 rads whole body irradiation at 2 and 9 weeks during this 10-week recovery period, the combined treatment (i.e., chemical mixture followed by irradiation) group showed a significantly slower recovery of bone marrow progenitors as compared with the control group (i.e., radiation but without prior chemical mixture treatment). This study showed that even 10 weeks after the cessation of chemical mixture treatment when all hematological parameters were normal, a residual effect of the chemical mixture may still be demonstrated as lower progenitor cell numbers following irradiation. Thus, residual damage of hematopoiesis in mice exposed to groundwater contaminants for 108 days renders the mice more sensitive to subsequent irradiation-induced injury. RP HONG, HL (reprint author), NIEHS,NATL TOXICOL PROGRAM,MD C202,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 53 TC 18 Z9 18 U1 1 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD JUN PY 1991 VL 57 IS 1 BP 101 EP 111 DI 10.1016/0378-4274(91)90124-O PG 11 WC Toxicology SC Toxicology GA FT633 UT WOS:A1991FT63300012 PM 2048155 ER PT J AU HEINEMANN, JA AF HEINEMANN, JA TI GENETICS OF GENE-TRANSFER BETWEEN SPECIES SO TRENDS IN GENETICS LA English DT Review ID AGROBACTERIUM TI-PLASMID; ESCHERICHIA-COLI; BACTERIAL CONJUGATION; DNA; REPLICATION; PLANTS; EVOLUTION; PROMOTE; ORIGIN; CELL AB Bacteria transfer genetic information to members of at least three of the five biological kingdoms. Gene transfer between species may play the same role as sex between members of a single species, providing genetic diversity and material for repair of genomic damage. RP HEINEMANN, JA (reprint author), NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840, USA. NR 32 TC 61 Z9 62 U1 0 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD JUN PY 1991 VL 7 IS 6 BP 181 EP 185 DI 10.1016/0168-9525(91)90433-Q PG 5 WC Genetics & Heredity SC Genetics & Heredity GA FM185 UT WOS:A1991FM18500004 PM 2068792 ER PT J AU ASANUMA, C AF ASANUMA, C TI MAPPING MOVEMENTS WITHIN A MOVING MOTOR MAP SO TRENDS IN NEUROSCIENCES LA English DT Editorial Material ID CORTEX; REORGANIZATION RP ASANUMA, C (reprint author), NIMH,CTR ANIM,NEUROPHYSIOL LAB,POOLESVILLE,MD 20837, USA. NR 13 TC 18 Z9 18 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD JUN PY 1991 VL 14 IS 6 BP 217 EP 218 DI 10.1016/0166-2236(91)90115-B PG 2 WC Neurosciences SC Neurosciences & Neurology GA FP801 UT WOS:A1991FP80100001 PM 1716010 ER PT J AU CRAWLEY, JN AF CRAWLEY, JN TI CHOLECYSTOKININ-DOPAMINE INTERACTIONS SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID POTENT ANXIOLYTIC ACTIVITY; B RECEPTOR ANTAGONISTS; VENTRAL TEGMENTAL AREA; NUCLEUS-ACCUMBENS; SUBSTANTIA NIGRA; HALOPERIDOL TREATMENT; FRONTAL-CORTEX; CCK RECEPTOR; RAT; BRAIN AB Cholecystokinin (CCK) coexists with dopamine in a large proportion of the ventral tegmental and substantia nigra neurons in rodents and primates. In this review Jacki Crawley integrates the neurophysiological, behavioral, and release studies which demonstrate both excitatory effects of CCK, and facilitatory modulating effects of CCK on the inhibitory actions of dopamine, in the mesolimbic pathway. Nonpeptide antagonists selective for the CCK(A) and CCK(B) receptors have recently been developed, and provide long-awaited tools to test hypotheses about the role of endogenous CCK as a modulator of dopaminergic function, and the potential of CCK-based drugs as treatments for neuropsychiatric disorders. RP CRAWLEY, JN (reprint author), NIMH,EXPTL THERAPEUT BRANCH,BEHAV NEUROPHARMACOL UNIT,BLDG 10,ROOM 4N214,BETHESDA,MD 20892, USA. NR 50 TC 242 Z9 245 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD JUN PY 1991 VL 12 IS 6 BP 232 EP 236 DI 10.1016/0165-6147(91)90558-A PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FP525 UT WOS:A1991FP52500008 PM 2048219 ER PT J AU MAITRA, RK AHMAD, N HOLLAND, SM VENKATESAN, S AF MAITRA, RK AHMAD, N HOLLAND, SM VENKATESAN, S TI HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) PROVIRUS EXPRESSION AND LTR TRANSCRIPTION ARE REPRESSED IN NEF-EXPRESSING CELL-LINES SO VIROLOGY LA English DT Article ID TRANS-ACTIVATOR GENE; NORMAL HUMAN-LYMPHOCYTES; VIRAL MESSENGER-RNA; III HTLV-III/LAV; REV PROTEIN; TARGET SEQUENCE; FUNCTIONAL-ANALYSIS; MUTATIONAL ANALYSIS; SECONDARY STRUCTURE; REPLICATION C1 NIH,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NIAID,BETHESDA,MD 20892. NR 53 TC 39 Z9 39 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 JUN PY 1991 VL 182 IS 2 BP 522 EP 533 DI 10.1016/0042-6822(91)90593-Z PG 12 WC Virology SC Virology GA FM141 UT WOS:A1991FM14100011 PM 2024488 ER PT J AU QIAN, Y JIANG, BM SAIF, LJ KANG, SY ISHIMARU, Y YAMASHITA, Y OSETO, M GREEN, KY AF QIAN, Y JIANG, BM SAIF, LJ KANG, SY ISHIMARU, Y YAMASHITA, Y OSETO, M GREEN, KY TI SEQUENCE CONSERVATION OF GENE-8 BETWEEN HUMAN AND PORCINE GROUP-C ROTAVIRUSES AND ITS RELATIONSHIP TO THE VP7 GENE OF GROUP-A ROTAVIRUSES SO VIROLOGY LA English DT Article ID ANTIGENICALLY DISTINCT ROTAVIRUSES; SEROTYPE-SPECIFIC GLYCOPROTEIN; CAPSID PROTEIN; OUTBREAK; DIARRHEA; PIGS; NEUTRALIZATION; POLYPEPTIDES; INFECTION; CLEAVAGE C1 NIAID, INFECT DIS LAB, BETHESDA, MD 20892 USA. OHIO STATE UNIV, OHIO AGR RES & DEV CTR, WOOSTER, OH 44691 USA. ISHIMARU CHILDRENS HOSP, MATSUYAMA, EHIME 790, JAPAN. EHIME PREFECTURAL INST PUBLIC HLTH, MATSUYAMA, EHIME 790, JAPAN. MATSUYAMA PREFECTURAL INST PUBLIC HLTH, MATSUYAMA, EHIME 790, JAPAN. NR 39 TC 34 Z9 36 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 0042-6822 J9 VIROLOGY JI Virology PD JUN PY 1991 VL 182 IS 2 BP 562 EP 569 DI 10.1016/0042-6822(91)90597-5 PG 8 WC Virology SC Virology GA FM141 UT WOS:A1991FM14100015 PM 1850919 ER PT J AU NICHOLAS, JA RUBINO, KL LEVELY, ME MEYER, AL COLLINS, PL AF NICHOLAS, JA RUBINO, KL LEVELY, ME MEYER, AL COLLINS, PL TI CYTOTOXIC T-CELL ACTIVITY AGAINST THE 22-KDA PROTEIN OF HUMAN RESPIRATORY SYNCYTIAL VIRUS (RSV) IS ASSOCIATED WITH A SIGNIFICANT REDUCTION IN PULMONARY RSV REPLICATION SO VIROLOGY LA English DT Article ID RECOMBINANT VACCINIA VIRUS; CHIMERIC FG GLYCOPROTEIN; COTTON RATS; MEDIATED-IMMUNITY; BACULOVIRUS VECTOR; LYMPHOCYTES-T; BALB/C MICE; INFECTION; EXPRESSION; IMMUNIZATION C1 UPJOHN LABS,DEPT MOLEC BIOL,KALAMAZOO,MI 49007. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. RP NICHOLAS, JA (reprint author), UPJOHN LABS,DEPT INFECT DIS,KALAMAZOO,MI 49007, USA. NR 39 TC 17 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JUN PY 1991 VL 182 IS 2 BP 664 EP 672 DI 10.1016/0042-6822(91)90607-D PG 9 WC Virology SC Virology GA FM141 UT WOS:A1991FM14100025 PM 2024493 ER PT J AU MULHERKAR, R COULIER, F AF MULHERKAR, R COULIER, F TI OVEREXPRESSION OF HUMAN TRK PROTOONCOGENE INTO MOUSE CELLS USING AN INDUCIBLE VECTOR SYSTEM SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID BIOCHEMICAL-CHARACTERIZATION; PRODUCT RP MULHERKAR, R (reprint author), NCI,FREDERICK CANC RES FACIL,BASIC RES PROGRAM,DEV ONCOL SECT,FREDERICK,MD 21701, USA. RI Coulier, Francois/G-6098-2015 OI Coulier, Francois/0000-0002-6288-7773 NR 11 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 31 PY 1991 VL 177 IS 1 BP 90 EP 96 DI 10.1016/0006-291X(91)91952-9 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FP415 UT WOS:A1991FP41500014 PM 1645965 ER PT J AU CASTRONOVO, V CLAYSMITH, AP BARKER, KT CIOCE, V KRUTZSCH, HC SOBEL, ME AF CASTRONOVO, V CLAYSMITH, AP BARKER, KT CIOCE, V KRUTZSCH, HC SOBEL, ME TI BIOSYNTHESIS OF THE 67 KDA HIGH-AFFINITY LAMININ RECEPTOR SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID EXPRESSION; CELLS RP CASTRONOVO, V (reprint author), NCI,PATHOL LAB,TUMOR INVAS & METASTASIS SECT,BETHESDA,MD 20892, USA. NR 11 TC 84 Z9 84 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 31 PY 1991 VL 177 IS 1 BP 177 EP 183 DI 10.1016/0006-291X(91)91965-F PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FP415 UT WOS:A1991FP41500027 PM 1828340 ER PT J AU YU, YM BECVAR, R YAMADA, Y REDDI, AH AF YU, YM BECVAR, R YAMADA, Y REDDI, AH TI CHANGES IN THE GENE-EXPRESSION OF COLLAGENS, FIBRONECTIN, INTEGRIN AND PROTEOGLYCANS DURING MATRIX-INDUCED BONE MORPHOGENESIS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID AMINO-ACID SEQUENCE; CARTILAGE; CDNA; RAT; DIFFERENTIATION; CLONES; MARROW; RNA C1 NIDR,BONE CELL BIOL SECT,BETHESDA,MD 20892. NIDR,MOLEC BIOL SECT,BETHESDA,MD 20892. NR 18 TC 30 Z9 30 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 31 PY 1991 VL 177 IS 1 BP 427 EP 432 DI 10.1016/0006-291X(91)92001-Z PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FP415 UT WOS:A1991FP41500063 PM 2043127 ER PT J AU JASKIW, GE TIZABI, Y LIPSKA, BK KOLACHANA, BS WYATT, RJ GILAD, GM AF JASKIW, GE TIZABI, Y LIPSKA, BK KOLACHANA, BS WYATT, RJ GILAD, GM TI EVIDENCE FOR A FRONTOCORTICAL SEPTAL GLUTAMATERGIC PATHWAY AND COMPENSATORY CHANGES IN SEPTAL GLUTAMATE UPTAKE AFTER CORTICAL AND FORNIX LESIONS IN THE RAT SO BRAIN RESEARCH LA English DT Article DE FRONTAL CORTEX; FORNIX; SEPTUM; NUCLEUS ACCUMBENS SEPTI; GLUTAMATE UPTAKE ID MEDIAL PREFRONTAL CORTEX; NUCLEUS ACCUMBENS; HIPPOCAMPAL EFFERENTS; BIOCHEMICAL-EVIDENCE; BASAL FOREBRAIN; PROJECTION; ANTEROGRADE; BRAIN; HYPOTHALAMUS; INNERVATION AB To determine the source of glutamatergic input to the septum and to the nucleus accumbens septi, glutamate uptake was assessed after transections of the frontal cortex and/or fornix. Uptake in the septum and accumbens was reduced by 25 and 30% respectively, 6 days after bilateral frontal cortex transections. Both indices returned to control levels 30 days postoperatively. In contrast, while unilateral fornix transection did not affect uptake in the accumbens at either day 6 or 30, uptake in the septum was significantly reduced (25-35%) at both times. When a unilateral transection of the fornix was performed in rats with a pre-existing bilateral ablation of the frontal cortex, a further reduction in uptake was observed in the septum (50-60% at both 6 and 30 days after the fornix transection). The data implicate glutamate as a neurotransmitter in frontocortico-septal projections and suggest that the contribution of the hippocampo-septal system to total glutamate uptake in the septum is increased following ablation of the frontocortico-septal system. C1 ST ELIZABETH HOSP,CTR NEUROSCI,WAW BLDG ROOM 435,WASHINGTON,DC 20032. ST ELIZABETH HOSP,NIMH,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. ST ELIZABETH HOSP,NIMH,INTRAMURAL RES PROGRAM,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. HOWARD UNIV,COLL MED,DEPT PHARMACOL,WASHINGTON,DC 20059. NR 27 TC 30 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 31 PY 1991 VL 550 IS 1 BP 7 EP 10 DI 10.1016/0006-8993(91)90398-F PG 4 WC Neurosciences SC Neurosciences & Neurology GA FR348 UT WOS:A1991FR34800002 PM 1889003 ER PT J AU BAKER, ME FANESTIL, DD AF BAKER, ME FANESTIL, DD TI MAMMALIAN PERIPHERAL-TYPE BENZODIAZEPINE RECEPTOR IS HOMOLOGOUS TO CRTK PROTEIN OF RHODOBACTER-CAPSULATUS, A PHOTOSYNTHETIC BACTERIUM SO CELL LA English DT Letter ID CHOLESTEROL; MEMBRANES; OUTER C1 UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. RP BAKER, ME (reprint author), NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892, USA. OI Baker, Michael/0000-0003-4387-3269 NR 16 TC 32 Z9 33 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD MAY 31 PY 1991 VL 65 IS 5 BP 721 EP 722 DI 10.1016/0092-8674(91)90379-D PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FP516 UT WOS:A1991FP51600003 PM 1645618 ER PT J AU SOPPET, D ESCANDON, E MARAGOS, J MIDDLEMAS, DS REID, SW BLAIR, J BURTON, LE STANTON, BR KAPLAN, DR HUNTER, T NIKOLICS, K PARADA, LF AF SOPPET, D ESCANDON, E MARAGOS, J MIDDLEMAS, DS REID, SW BLAIR, J BURTON, LE STANTON, BR KAPLAN, DR HUNTER, T NIKOLICS, K PARADA, LF TI THE NEUROTROPHIC FACTORS BRAIN-DERIVED NEUROTROPHIC FACTOR AND NEUROTROPHIN-3 ARE LIGANDS FOR THE TRKB TYROSINE KINASE RECEPTOR SO CELL LA English DT Article ID NERVE GROWTH-FACTOR; PDGF BETA-RECEPTOR; MOLECULAR-CLONING; FACTOR FAMILY; SIGNALING COMPLEX; MESSENGER-RNA; GENE-TRANSFER; EXPRESSION; ONCOGENE; CELLS AB Neurotrophic factors are essential for neuronal survival and function. Recent data have demonstrated that the product of the tyrosine kinase trk protooncogene binds NGF and is a component of the high affinity NGF receptor. Analysis of the trkB gene product, gp145trkB, in NIH 3T3 cells indicates that this tyrosine kinase receptor is rapidly phosphorylated on tyrosine residues upon exposure to the NGF-related neurotrophic factors BDNF and NT-3. Furthermore, gp145trkB specifically binds BDNF and NT-3 in NIH 3T3 cells and in hippocampal cells,but does not bind NGF. Thus, the trk family of receptors are likely to be important signal transducers of NGF-related trophic signals in the formation and maintenance of neuronal circuits. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,EUKARYOT SIGNAL TRANSDUCT GRP,FREDERICK,MD 21702. GENENTECH INC,DEPT DEV BIOL,S SAN FRANCISCO,CA 94080. SALK INST BIOL STUDIES,SAN DIEGO,CA 92186. RP SOPPET, D (reprint author), NCI,FREDERICK CANC RES & DEV CTR,MOLEC EMBRYOL SECT,FREDERICK,MD 21702, USA. RI Parada, luis/B-9400-2014 FU NCI NIH HHS [N01-CO-74101] NR 56 TC 641 Z9 648 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD MAY 31 PY 1991 VL 65 IS 5 BP 895 EP 903 DI 10.1016/0092-8674(91)90396-G PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FP516 UT WOS:A1991FP51600019 PM 1645620 ER EF