FN Thomson Reuters Web of Science™ VR 1.0 PT J AU GLOTH, FM TOBIN, JD HOLLIS, BW GUNDBERG, CM AF GLOTH, FM TOBIN, JD HOLLIS, BW GUNDBERG, CM TI LACK OF RELATIONSHIP BETWEEN SERUM LEVELS OF OSTEOCALCIN AND VITAMIN-D STATUS IN THE ELDERLY SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. NIA,BALTIMORE,MD 21224. MED UNIV S CAROLINA,CHARLESTON,SC 29425. YALE UNIV,SCH MED,NEW HAVEN,CT 06510. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1992 VL 7 SU 1 BP S167 EP S167 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JL595 UT WOS:A1992JL59500300 ER PT J AU GRZESIK, WJ ROBEY, PG AF GRZESIK, WJ ROBEY, PG TI THE EFFECT OF EXTRACELLULAR-MATRIX GLYCOPROTEINS ON PROTEOGLYCAN SYNTHESIS AND SECRETION BY HUMAN BONE-CELLS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1992 VL 7 SU 1 BP S221 EP S221 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JL595 UT WOS:A1992JL59500513 ER PT J AU HEEGAARD, AM ROBEY, PG VOGEL, W VETTER, U YOUNG, MF AF HEEGAARD, AM ROBEY, PG VOGEL, W VETTER, U YOUNG, MF TI THE BIGLYCAN PROMOTER IS DIFFERENTIALLY REGULATED IN TURNERS SYNDROME AND IN TRIPLE-X FEMALES SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV ULM,KLIN GENET ABT,W-7900 ULM,GERMANY. NIDR,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1992 VL 7 SU 1 BP S106 EP S106 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JL595 UT WOS:A1992JL59500056 ER PT J AU KERR, JM FISHER, LW TERMINE, JD WANG, MG MCBRIDE, OW YOUNG, MF AF KERR, JM FISHER, LW TERMINE, JD WANG, MG MCBRIDE, OW YOUNG, MF TI CHARACTERIZATION OF THE HUMAN BONE SIALOPROTEIN GENE SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. ELI LILLY & CO,INDIANAPOLIS,IN 46285. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1992 VL 7 SU 1 BP S134 EP S134 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JL595 UT WOS:A1992JL59500167 ER PT J AU NOLAN, EM HELMAN, LJ DEFTOS, LJ AF NOLAN, EM HELMAN, LJ DEFTOS, LJ TI A HUMAN CHROMOGRANIN-A (CGA) FUSION PROMOTER IS EXPRESSED IN CALCITONIN-POSITIVE NEUROENDOCRINE CELLS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. VET AFFAIRS MED CTR,LA JOLLA,CA. NCI,PEDIAT BRANCH,MOLEC GENET SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1992 VL 7 SU 1 BP S236 EP S236 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JL595 UT WOS:A1992JL59500575 ER PT J AU PANICCIA, R GRANO, M GEHRONROBEY, P ZALLONE, AZ TETI, A AF PANICCIA, R GRANO, M GEHRONROBEY, P ZALLONE, AZ TETI, A TI RECOGNITION OF BSPII AND OSTEOPONTIN RGD-CONTAINING PEPTIDES REGULATES [CA2+]I IN HUMAN OSTEOCLAST-LIKE CELLS - REGULATION BY PHORBOL ESTERS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV BARI,INST HUMAN ANAT,I-70124 BARI,ITALY. NIDR,BONE RES BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1992 VL 7 SU 1 BP S251 EP S251 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JL595 UT WOS:A1992JL59500632 ER PT J AU SHENKER, A SWEET, DE SPIEGEL, AM WEINSTEIN, LS AF SHENKER, A SWEET, DE SPIEGEL, AM WEINSTEIN, LS TI AN ACTIVATING GS-ALPHA MUTATION IS PRESENT IN FIBROUS DYSPLASIA OF BONE IN THE MCCUNE-ALBRIGHT SYNDROME SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDDK,MOLEC PATHOPHYSIOL BRANCH,BETHESDA,MD 20892. ARMED FORCES INST PATHOL,WASHINGTON,DC 20306. NR 0 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1992 VL 7 SU 1 BP S115 EP S115 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JL595 UT WOS:A1992JL59500089 ER PT J AU SOARES, JH SHELLEM, TA WOODS, LC KERR, JM AF SOARES, JH SHELLEM, TA WOODS, LC KERR, JM TI EVIDENCE OF THE VITAMIN-N-D ENDOCRINE SYSTEM IN THE GILL OF STRIPED BASS (MORONE-SAXATILIS) SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV MARYLAND,MAES,COLL PK,MD 20742. UNIV MARYLAND,COLL AGR,COLL PK,MD 20742. NIDR,BONE RES BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1992 VL 7 SU 1 BP S166 EP S166 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JL595 UT WOS:A1992JL59500293 ER PT J AU SPECKER, B VIEIRA, N OBRIEN, K HO, M HEUBI, J ABRAMS, S YERGEY, A AF SPECKER, B VIEIRA, N OBRIEN, K HO, M HEUBI, J ABRAMS, S YERGEY, A TI EFFECT OF LACTATION AND DIETARY CALCIUM ON CALCIUM KINETICS USING DUAL-TRACER STABLE ISOTOPES SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV CINCINNATI,MED CTR,CINCINNATI,OH 45267. NICHHD,BETHESDA,MD. CHILDRENS NUTR RES CTR,HOUSTON,TX 77030. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1992 VL 7 SU 1 BP S295 EP S295 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JL595 UT WOS:A1992JL59500807 ER PT J AU TOBIN, J SHERMAN, S PLATO, C GUNDBERG, C NIELSEN, L KUNG, V SEYEDIN, S AF TOBIN, J SHERMAN, S PLATO, C GUNDBERG, C NIELSEN, L KUNG, V SEYEDIN, S TI URINE PYRIDINOLINE (PYD) IS RELATED TO SERUM OSTEOCALCIN (OC) IN NORMAL MEN AND WOMEN - AGE AND SEX CONTRASTS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIA,BALTIMORE,MD 21224. YALE UNIV,NEW HAVEN,CT 06520. METRA BIOSYST,PALO ALTO,CA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1992 VL 7 SU 1 BP S178 EP S178 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JL595 UT WOS:A1992JL59500343 ER PT J AU VANDERPLUIJM, G BAAS, C PAPAPOULOS, S ROBEY, PG LOWIK, C AF VANDERPLUIJM, G BAAS, C PAPAPOULOS, S ROBEY, PG LOWIK, C TI INTEGRIN-MEDIATED ATTACHMENT OF BREAST-CANCER CELLS (MCF-7) TO EXTRACELLULAR BONE-MATRIX SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 LEIDEN UNIV HOSP,DEPT ENDOCRINOL,2333 AA LEIDEN,NETHERLANDS. NIDR,BRB,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1992 VL 7 SU 1 BP S133 EP S133 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JL595 UT WOS:A1992JL59500164 ER PT J AU VUKICEVIC, S CHEN, P REDDI, AH SAMPATH, TK AF VUKICEVIC, S CHEN, P REDDI, AH SAMPATH, TK TI LOCALIZATION OF THE OSTEOGENIC PROTEIN-1 (BONE MORPHOGENETIC PROTEIN-7) DURING EARLY HUMAN EMBRYONIC-DEVELOPMENT SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. CREAT BIOMOLEC,HOPKINKTON,MA 01748. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1992 VL 7 SU 1 BP S256 EP S256 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JL595 UT WOS:A1992JL59500654 ER PT J AU YU, XP RICE, N MANOLAGAS, SC AF YU, XP RICE, N MANOLAGAS, SC TI REGULATION OF NF-KB AND OTHER REL-RELATED PROTEINS IN ACTIVATED NORMAL HUMAN-LYMPHOCYTES BY 1,25(OH)2D3 SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 RICHARD L ROUDEBUSH VET ADM MED CTR,ENDOCRINOL & METAB SECT,INDIANAPOLIS,IN 46202. INDIANA UNIV,DEPT MED,INDIANAPOLIS,IN 46204. NCI,BASIC RES PROGRAM,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1992 VL 7 SU 1 BP S159 EP S159 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JL595 UT WOS:A1992JL59500268 ER PT J AU JOHNSON, GR SAEKI, T GORDON, AW SHOYAB, M SALOMON, DS STROMBERG, K AF JOHNSON, GR SAEKI, T GORDON, AW SHOYAB, M SALOMON, DS STROMBERG, K TI AUTOCRINE ACTION OF AMPHIREGULIN IN A COLON-CARCINOMA CELL-LINE AND IMMUNOCYTOCHEMICAL LOCALIZATION OF AMPHIREGULIN IN HUMAN COLON SO JOURNAL OF CELL BIOLOGY LA English DT Article ID GROWTH FACTOR-ALPHA; MESSENGER-RNA; EPITHELIAL-CELLS; FACTOR-RECEPTOR; TGF-ALPHA; EXPRESSION; EGF; TRANSFORMATION; FAMILY; GENE AB Amphiregulin (AR) is a newly discovered glycosylated, 84-amino acid residue polypeptide growth regulator which has sequence homology to the EGF family of proteins. To obtain immunological reagents to study the biological role of AR, two synthetic peptides containing sequences corresponding to distinct regions of AR were used to generate polyclonal antibodies in rabbits. One preparation of antipeptide antibodies directed against residues 26-44 of AR (AR-Ab2) was most effective in the detection of native AR, whereas another preparation of antibodies against residues 8-26 (AR-Ab1) was found to be most efficacious in the detection of AR in formalin-fixed and paraffin-embedded tissues. The growth of a colon carcinoma cell line, Geo, which proliferates autonomously under serum-free conditions, was stimulated by the exogenous addition of AR or EGF. Half-maximal stimulation of this growth was observed at 40 and 200 pM of EGF and AR, respectively. A mAb to the extracellular domain of the EGF receptor blocked the stimulation of cell proliferation induced by the exogenous addition of AR, suggesting that this stimulation was mediated via the EGF receptor. Geo cells were found to constitutively express significant levels of the AR mRNA transcript as determined by analysis of the polymerase chain reaction-amplified cDNA product and AR protein was detected immunocytochemically using the AR-Ab1 antibodies in these cells. AR was immunoprecipitated specifically using the AR-Ab2 antibodies from the conditioned medium of Geo cells, which had been metabolically labeled with [S-35]cysteine. The secreted AR migrated as a broad band (18.5-22.5 kD) with a median molecular weight of approximately 20.7 kD in SDS-PAGE. Immunospecific removal of AR from serum-free medium conditioned by the Geo cells and readdition of the AR-depleted medium to Geo cells resulted in an approximately 40% inhibition of cell growth relative to controls. Furthermore, the growth of the Geo cells was also inhibited by approximately 50% by the addition of the anti-EGF receptor mAb alone. These results indicate that AR and the EGF receptor are involved in the autocrine growth of these cells and suggests that AR may act through the EGF receptor via an extracellular autocrine loop. To study the expression of AR in human colon in vivo, AR was localized immunocytochemically in formalin-fixed, paraffin-embedded sections from normal and malignant human colon using the AR-Abl antibodies. In all normal colon specimens, AR was localized to the cytoplasm and nucleus of the terminally differentiated, non-proliferative surface columnar and secretory epithelial cells of the mucosa, but was not detectable in the proliferative epithelial cells of the crypts. In four out of five colonic carcinomas, AR was localized to the cytoplasm and/or nucleus of the cells. In conclusion, AR can act as an autocrine growth stimulator for colonic carcinoma cells in vitro and may perform a growth regulatory function in normal and malignant colon in vivo. C1 BRISTOL MYERS SQUIBB PHARMACEUT RES INST,SEATTLE,WA 98121. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. RP JOHNSON, GR (reprint author), US FDA,DIV CYTOKINE BIOL,CELL BIOL LAB,HFB-830,BLDG 29A,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 45 TC 138 Z9 141 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD AUG PY 1992 VL 118 IS 3 BP 741 EP 751 DI 10.1083/jcb.118.3.741 PG 11 WC Cell Biology SC Cell Biology GA JF804 UT WOS:A1992JF80400023 PM 1639855 ER PT J AU HENNIGHAUSEN, L AF HENNIGHAUSEN, L TI THE PROSPECTS FOR DOMESTICATING MILK PROTEIN GENES SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE MAMMARY GLAND; MILK PROTEIN GENES; BIOREACTOR; BIOTECHNOLOGY; GENE REGULATION ID WHEY ACIDIC PROTEIN; BETA-CASEIN GENE; HIGH-LEVEL EXPRESSION; ALPHA-LACTALBUMIN GENE; TISSUE PLASMINOGEN-ACTIVATOR; PROMOTER DIRECTS EXPRESSION; TRANSGENIC MICE; MAMMARY-GLAND; HORMONAL-REGULATION; UPSTREAM SEQUENCES AB It is possible to convert milk glands of transgenic animals into bioreactors producing heterologous proteins such as scarce human pharmaceuticals. To predictably and successfully engineer the milk gland, we will need a thorough understanding of its physiology. Expression studies in transgenic animals have located mammary specific and hormone inducible transcription elements in the promoter/upstream regions of milk protein genes, and transfection studies in cell lines or primary cells have identified constitutive and hormone inducible elements. Most importantly, it appears that in addition to individual promoter based transcription elements structural features of milk protein chromosomal loci may contribute to the tight developmental and hormonal regulation. I will discuss milk protein gene regulation with emphasis on regulatory differences between genes and species, and the possibility that transcription elements function only properly within genetically defined chromatin domains. Novel strategies to build mammary expression vectors and to test their functionality without pursuing the standard transgenic route will be presented. Finally, I will discuss homologous recombination with the goal to target milk protein genes. Only through the domestication of milk protein genes will we be able to use their full potential in the mammary bioreactor. RP HENNIGHAUSEN, L (reprint author), NIDDK,BIOCHEM & METAB LAB,BIOCHEM & METAB LAB,BLDG 10,RM 9N113,BETHESDA,MD 20982, USA. NR 70 TC 29 Z9 34 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD AUG PY 1992 VL 49 IS 4 BP 325 EP 332 DI 10.1002/jcb.240490402 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JG892 UT WOS:A1992JG89200001 PM 1429860 ER PT J AU RUNDHAUG, JE GRAY, T STEIGERWALT, RW NETTESHEIM, P AF RUNDHAUG, JE GRAY, T STEIGERWALT, RW NETTESHEIM, P TI CHANGES IN RESPONSIVENESS OF RAT TRACHEAL EPITHELIAL-CELLS TO TRANSFORMING GROWTH FACTOR-BETA-1 WITH TIME IN CULTURE SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID FACTOR TYPE-BETA; MESSENGER-RNAS; TGF-BETA; TERMINAL DIFFERENTIATION; SQUAMOUS DIFFERENTIATION; NEOPLASTIC PROGRESSION; NEGATIVE REGULATION; GENE-EXPRESSION; CARCINOMA-CELLS; PROLIFERATION AB Primary rat tracheal, epithelial (RTE) cell cultures have previously been shown to be highly sensitive to growth inhibition by transforming growth factor-beta-1 (TGF-beta-1) when treated within 1-2 days after plating. The purpose of the present studies was to examine the effects of TGF-beta-1 on the growth of RTE cells as a function of time in culture. We found that the sensitivity of RTE cells to growth inhibition by TGF-beta-1 decreased dramatically as the cultures aged. The IC50 for inhibition of colony forming efficiency was 0.18 pM when TGF-beta-1 was added 24 h after cell plating. When TGF-beta-1 treatment was begun on day 5 of culture, the IC50 was 3-4 pM as measured by inhibition of growth (cell number) and DNA synthesis. However, when TGF-beta-1 was begun on day 19, the IC50 was 65 pM, depending on whether inhibition of growth or DNA synthesis, respectively, was measured. TGF-beta-1 accelerated cell death, as measured by exfoliation of cells, and inhibited cell proliferation. The decrease in responsiveness to TGF-beta-1 in late cultures was shown to be dependent on culture age as well as on cell density. No evidence was found for inactivation or degradation of the added TGF-beta-1 by the late stage cultures. Cells subcultured from late stage primary cultures remained less responsive to TGF-beta-1 than subcultured cells from early cultures. Similar to its effect on proliferation, TGF-beta-1 down-regulated the expression of two proliferation-related genes, c-myc and transforming growth factor-alpha, in early but not late RTE cell cultures. On the other hand, fibronectin expression was increased by TGF-beta-1 by about twofold at both early and late times in culture. This indicates that the changes in TGF-beta-1 responsiveness with time in culture are selective, apparently affecting primarily proliferation-related events. C1 NIEHS,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC 27709. NR 46 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD AUG PY 1992 VL 152 IS 2 BP 281 EP 291 DI 10.1002/jcp.1041520209 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA JF663 UT WOS:A1992JF66300008 PM 1639863 ER PT J AU FERRIOLA, PC ROBERTSON, AT RUSNAK, DW DIAUGUSTINE, R NETTESHEIM, P AF FERRIOLA, PC ROBERTSON, AT RUSNAK, DW DIAUGUSTINE, R NETTESHEIM, P TI EPIDERMAL GROWTH-FACTOR DEPENDENCE AND TGF-ALPHA AUTOCRINE GROWTH-REGULATION IN PRIMARY RAT TRACHEAL EPITHELIAL-CELLS SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID ANTERIOR-PITUITARY GLAND; MESSENGER-RNA; PHORBOL ESTER; GENE-EXPRESSION; DISPERSED CELLS; FACTOR RECEPTOR; EGF RECEPTOR; MIGRATION; PROLIFERATION; LOCALIZATION AB We have examined dependence of primary rat tracheal epithelial (RTE) on exogenous epidermal growth factor (EGF) and determined whether a TGF-alpha autocrine pathway is operating in these cells. Primary RTE cells plated in serum free media (SFM) without EGF and bovine pituitary factor (BPE) show little proliferation compared to cultures propagated in media containing EGF/BPE (CSFM). Removal of EGF/BPE shortly after plating, however, results in significant proliferation, although plateau cell densities are reduced and cell morphology is significantly altered compared to cells propagated in CSFM. Addition of EGF and/or BPE to cultures propagated in SFM minus EGF/BPE restores maximum cell density. The concentration of TGF-alpha peptide in media conditioned by cells propagated without EGF/BPE is lower than the concentration in the media of CSFM cultures. TGF-alpha mRNA and protein levels are also significantly lower in cells late in culture compared to logarithmically growing cells regardless of the presence or absence of EGF/BPE. The proliferation of primary RTE cells propagated without EGF/BPE is inhibited by neutralizing TGF-alpha antiserum and by a tyrphostin compound that blocks TGF-alpha/EGF receptor tyrosine kinase activity. These results indicate that primary RTE cells utilize TGF-alpha as an autocrine growth factor and that the autocrine pathway is regulated as a function of growth state of the cells. However, this pathway does not provide growth autonomy to primary RTE cells, since cultures remain dependent on exogenous EGF/BPE for sustained proliferation. C1 NIEHS,BIOCHEM RISK ANAL LABS,RES TRIANGLE PK,NC 27709. RP FERRIOLA, PC (reprint author), NIEHS,PULM PATHOBIOL LABS,EPITHELIAL CARCINOGENESIS GRP,RES TRIANGLE PK,NC 27709, USA. NR 33 TC 25 Z9 25 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD AUG PY 1992 VL 152 IS 2 BP 302 EP 309 DI 10.1002/jcp.1041520211 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA JF663 UT WOS:A1992JF66300010 PM 1639864 ER PT J AU STREETEN, EA WEINSTEIN, LS NORTON, JA MULVIHILL, JJ WHITE, BJ FRIEDMAN, E JAFFE, G BRANDI, ML STEWART, K ZIMERING, MB SPIEGEL, AM AURBACH, GD MARX, SJ AF STREETEN, EA WEINSTEIN, LS NORTON, JA MULVIHILL, JJ WHITE, BJ FRIEDMAN, E JAFFE, G BRANDI, ML STEWART, K ZIMERING, MB SPIEGEL, AM AURBACH, GD MARX, SJ TI STUDIES IN A KINDRED WITH PARATHYROID CARCINOMA SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FAMILIAL HYPERPARATHYROIDISM; NEOPLASIA; DIAGNOSIS; CANCER; ADENOMAS; GLAND AB We report a family with primary hyperparathyroidism in four patients in two generations with apparent autosomal dominant transmission. A fifth member was probably affected. Two cases had definite parathyroid carcinoma (PC), and two had parathyroid adenoma with atypical features that could represent an early stage of cancer. In each of our patients, one parathyroid gland was abnormal. Five other parathyroid glands (in two patients) were normal in histology and size. There was no evidence of neoplasia in other tissues. Constitutional karyotypes were normal in all four patients. We identified three chromosomal abnormalities (a reciprocal translocation between chromosomes 3 and 4, trisomy 7, and a pericentric inversion in chromosome 9) in cultured PC tissue from one patient. These chromosomal changes are of unclear significance. Analyses on tumor DNA from one case of PC and one of atypical adenoma showed no evidence of ras gene mutations, PTH gene rearrangement, or allelic loss from chromosome 11q13 (locus of the gene for multiple endocrine neoplasia type 1). This family shows susceptibility to cancer without antecedent hyperplasia in all parathyroids. It could help identify a novel tumor susceptibility gene. C1 NIADDKD, METAB DIS BRANCH, BETHESDA, MD 20892 USA. NIADDKD, CHEM BIOL LAB, CYTOGENET UNIT, BETHESDA, MD 20892 USA. NCI, SURG BRANCH, BETHESDA, MD 20892 USA. OI Weinstein, Lee/0000-0002-1899-5152 NR 36 TC 36 Z9 37 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 1992 VL 75 IS 2 BP 362 EP 366 DI 10.1210/jc.75.2.362 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JG867 UT WOS:A1992JG86700006 PM 1639936 ER PT J AU CORPAS, E HARMAN, SM PINEYRO, MA ROBERSON, R BLACKMAN, MR AF CORPAS, E HARMAN, SM PINEYRO, MA ROBERSON, R BLACKMAN, MR TI GROWTH-HORMONE (GH)-RELEASING HORMONE-(1-29) TWICE DAILY REVERSES THE DECREASED GH AND INSULIN-LIKE GROWTH FACTOR-I LEVELS IN OLD MEN SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SOMATOMEDIN-C LEVELS; AGE-RELATED-CHANGES; CONTINUOUS INFUSION; BODY-COMPOSITION; SECRETION; DEFICIENCY; YOUNG; SERUM; WOMEN; RADIOIMMUNOASSAY AB Aging is associated with decreased GH and insulin-like growth factor-I (IGF-I) levels and lean body mass, and increased body fat. Recombinant human GH treatment of old men partially reverses body composition changes. Administration of GH-releasing hormone (GHRH) to GH-deficient children and young adults increases GH and IGF-I levels while preserving physiological GH release. We investigated whether GHRH injections restore GH and IGF-I levels in old men to the levels in young men. Healthy young (n = 9; 26.2 +/- 4.1 yr; mean +/- SD) and old (n = 10; 68.0 +/- 6.2 yr) nonobese men underwent baseline blood sampling for measurements of IGF-I and 24-h profiles of GH release, followed by iv bolus GHRH stimulation tests. Old men then took, randomly, both low (0.5 mg) and high (1 mg) dose GHRH-(1-29) sc injections twice daily for 14 days, with an intervening 14-day nontreatment period. The study protocol was repeated on day 14 of each treatment. At baseline, the mean peak duration of spontaneous GH release (P < 0.005) and IGF-I levels (P < 0.0001) were lower in the old men. GHRH treatment evoked dose-related increases in all parameters, with significant differences (vs. old basal values) in mean 24-h GH (P < 0.001), area under peaks (P < 0.001), peak amplitude (P < 0.05), and IGF-I (P < 0.005) only at the high dose. After high dose treatment, there were no significant differences in these parameters between age groups. Peak and integrated responses to iv GHRH stimulation tests did not differ between young and old men either before or during GHRH treatment. Baseline serum levels of both testosterone (P < 0.01) and phosphate (P < 0.05) were lower in the older men. Phosphate levels increased (P < 0.05) during GHRH treatment. GHRH treatment did not affect fasting glucose, urinary C-peptide, blood pressure, or chemistry and hematology profiles. Thus, short term sc administration of GHRH to healthy old men reverses age-related decreases in GH and IGF-I, suggesting that prolonged treatment could improve age-related alterations in body composition. C1 JOHNS HOPKINS UNIV, SCH MED, DEPT MED, BALTIMORE, MD 21224 USA. FRANCIS SCOTT KEY MED CTR, DEPT MED, BALTIMORE, MD 21224 USA. RP CORPAS, E (reprint author), NIA, GERONTOL RES CTR,CLIN PHYSIOL LAB,ENDOCRINOL SECT, ROOM 2B19, 4940 EASTERN AVE, BALTIMORE, MD 21224 USA. FU NCRR NIH HHS [MO1-RR-02719] NR 48 TC 144 Z9 145 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 1992 VL 75 IS 2 BP 530 EP 535 DI 10.1210/jc.75.2.530 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JG867 UT WOS:A1992JG86700037 PM 1379256 ER PT J AU LENFANT, C WILLIAMS, TF AF LENFANT, C WILLIAMS, TF TI PRUDENCE AND EVIDENCE IN DISEASE PREVENTION SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Letter C1 UNIV ROCHESTER,ROCHESTER,NY 14627. NIA,BETHESDA,MD 20892. RP LENFANT, C (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 8 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 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD AUG PY 1992 VL 45 IS 8 BP 925 EP 926 DI 10.1016/0895-4356(92)90077-Z PG 2 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA JE250 UT WOS:A1992JE25000016 PM 1624976 ER PT J AU SNELLER, MC STRAUS, SE JAFFE, ES JAFFE, JS FLEISHER, TA STETLERSTEVENSON, M STROBER, W AF SNELLER, MC STRAUS, SE JAFFE, ES JAFFE, JS FLEISHER, TA STETLERSTEVENSON, M STROBER, W TI A NOVEL LYMPHOPROLIFERATIVE AUTOIMMUNE SYNDROME RESEMBLING MURINE LPR/GLD DISEASE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE AUTOIMMUNITY; DOUBLE-NEGATIVE; HUMAN; T-CELL RECEPTOR ALPHA/BETA CHAINS ID T-CELL RECEPTOR; HUMAN LYMPHOCYTES-T; MRL-LPR/LPR MICE; MONOCLONAL-ANTIBODY; AUTOANTIBODY PRODUCTION; CYTOLYTIC ACTIVITY; GENE-EXPRESSION; LPR MICE; PROLIFERATION; VIRUS AB In mice, the two distinct autosomal recessive genes lpr and gld can induce a syndrome characterized by autoantibody formation and the progressive accumulation of an unusual CD4-CD8- T cell population in peripheral lymphoid tissue. This phenotype does not precisely mirror any human disease. In this report we describe two patients with a progressive lymphoproliferative disorder associated with autoimmunity. The peripheral blood and lymph nodes of these patients contained large numbers of an unusual CD4-CD8- T cell population. These CD4 -CD8- T cells express surface markers characteristic of mature peripheral blood T cells (CD3, CD2, CD5), express the alpha/beta-form of the T cell receptor, and do not express surface markers characteristic of immature thymocytes (CD1) or NK cells (CD16, CD56). Functionally, these cells exhibited deficient proliferation and lymphokine production upon stimulation with mitogenic antibodies to CD3 or CD2. Both proliferation and lymphokine production could be augmented by co-stimulation with an antibody directed at the CD28 determinant. The clinical and immunological features of this syndrome resemble the lymphoproliferative/autoimmune disease seen in lpr and gld mice. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NIH,CTR CLIN,IMMUNOL SERV,BETHESDA,MD 20892. RP SNELLER, MC (reprint author), NIAID,CLIN INVEST LAB,BLDG 10,ROOM 11N 250,BETHESDA,MD 20892, USA. NR 35 TC 215 Z9 220 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 1992 VL 90 IS 2 BP 334 EP 341 DI 10.1172/JCI115867 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JH801 UT WOS:A1992JH80100006 PM 1386609 ER PT J AU DEBINSKI, W KARLSSON, B LINDHOLM, L SIEGALL, CB WILLINGHAM, MC FITZGERALD, D PASTAN, I AF DEBINSKI, W KARLSSON, B LINDHOLM, L SIEGALL, CB WILLINGHAM, MC FITZGERALD, D PASTAN, I TI MONOCLONAL-ANTIBODY C242-PSEUDOMONAS EXOTOXIN-A - A SPECIFIC AND POTENT IMMUNOTOXIN WITH ANTITUMOR-ACTIVITY ON A HUMAN COLON CANCER XENOGRAFT IN NUDE-MICE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE COLON CANCER; IMMUNOTOXINS; PSEUDOMONAS EXOTOXIN-A; SOLID TUMOR THERAPY ID PSEUDOMONAS EXOTOXIN; ESCHERICHIA-COLI; DOMAIN-II; RAT AB Two immunotoxins were constructed by chemically coupling the monoclonal antibody C242 to Pseudomonas exotoxin A (PE) or a modified form, NlysPE40, that lacks the cell binding domain of PE. Monoclonal antibody C242 recognizes a specific sialylated carbohydrate epitope on a high molecular weight membrane glycoprotein present on cells of human colon, pancreatic, and cervical cancers. C242-PE and C242-NlysPE40 were very cytotoxic for cells expressing this antigen with 50% inhibition of protein synthesis occurring on Colo205 cells at 0.2 ng/ml (0.9 pM) for C242-PE and 6.0 ng/ml (31 pM) for C242-NlysPE40. The two immunotoxins also exhibited a strong antitumor effect on a human colon cancer xenograft grown in nude mice. The specificity and potency of these two C242 immunotoxins warrant their further development for the treatment of cancer. C1 PHARM CANAG,S-40242 GOTHENBURG,SWEDEN. RP PASTAN, I (reprint author), NCI,DIV CANC BIOL DIAGNOSIS & CTR,MOLEC BIOL LAB,BLDG 37,ROOM 4E16,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA-12197]; NCRR NIH HHS [RR-04869] NR 21 TC 36 Z9 36 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 1992 VL 90 IS 2 BP 405 EP 411 DI 10.1172/JCI115875 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JH801 UT WOS:A1992JH80100014 PM 1644913 ER PT J AU FELIX, CA DAMICO, D MITSUDOMI, T NAU, MM LI, FP FRAUMENI, JF COLE, DE MCCALLA, J REAMAN, GH WHANGPENG, J KNUTSEN, T MINNA, JD POPLACK, DG AF FELIX, CA DAMICO, D MITSUDOMI, T NAU, MM LI, FP FRAUMENI, JF COLE, DE MCCALLA, J REAMAN, GH WHANGPENG, J KNUTSEN, T MINNA, JD POPLACK, DG TI ABSENCE OF HEREDITARY P53 MUTATIONS IN 10 FAMILIAL LEUKEMIA PEDIGREES SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Note DE ACUTE LYMPHOBLASTIC LEUKEMIA; GERMLINE MUTATION; SOMATIC MUTATION; TUMOR SUPPRESSOR GENE ID ACUTE LYMPHOBLASTIC-LEUKEMIA; TUMOR SUPPRESSOR GENE; CELL LUNG-CANCER; T-CELL; CHROMOSOME-CHANGES; MUTANT P53; SARCOMAS; NEOPLASMS; CHILDHOOD; ONCOGENE AB Germline p53 mutations have been identified in the Li-Fraumeni syndrome but the role of such mutations in familial leukemia is not established. The p53 gene was examined by single-strand conformation polymorphism analysis of exons 4-8 in 10 families with multiple members affected with leukemia. The diagnoses included acute and chronic leukemias and Hodgkin's disease. Identified in two families were p53 mutations that were nonhereditary. These included a 2-bp deletion in exon 6 found in the lymphoblast DNA of one child whose sibling, cousin, and several adult relatives had acute leukemia. The other nonhereditary p53 mutation was a transition at codon 248 (CGG to CAG, arginine to glutamine) found in the lymphoblasts of a patient with a preleukemic syndrome and acute lymphoblastic leukemia (ALL) whose brother is a long-term survivor of ALL. Thus, p53 mutations were found to occur in two families but both were nonhereditary. Moreover, in the remaining eight families no p53 mutation was identified in the regions of p53 where most mutations have been found in other cancers. Although p53 mutations sometimes may be present, they do not appear to be a primary event responsible for hereditary susceptibility to familial leukemia. This study suggests involvement of other genes or mechanisms. C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20892. NCI,EPIDEMIOL BRANCH,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,NATL CANC INST,BOSTON,MA 02115. GEORGE WASHINGTON UNIV,CHILDRENS NATL MED CTR,DIV HEMATOL ONCOL,WASHINGTON,DC 20010. UNIV TEXAS,SW MED CTR,SIMMONS CANC RES CTR,DALLAS,TX 75235. RP FELIX, CA (reprint author), CHILDRENS HOSP PHILADELPHIA,DEPT PEDIAT,DIV ONCOL,ROOM 9093,34TH ST & CIV CTR BLVD,PHILADELPHIA,PA 19104, USA. OI Mitsudomi, Tetsuya/0000-0001-9860-8505 NR 31 TC 42 Z9 42 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 1992 VL 90 IS 2 BP 653 EP 658 DI 10.1172/JCI115907 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JH801 UT WOS:A1992JH80100046 PM 1644930 ER PT J AU BELSHE, RB KARRON, RA NEWMAN, FK ANDERSON, EL NUGENT, SL STEINHOFF, M CLEMENTS, ML WILSON, MH HALL, SL TIERNEY, EL MURPHY, BR AF BELSHE, RB KARRON, RA NEWMAN, FK ANDERSON, EL NUGENT, SL STEINHOFF, M CLEMENTS, ML WILSON, MH HALL, SL TIERNEY, EL MURPHY, BR TI EVALUATION OF A LIVE ATTENUATED, COLD-ADAPTED PARAINFLUENZA VIRUS TYPE-3 VACCINE IN CHILDREN SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID TEMPERATURE-SENSITIVE PHENOTYPE; WEANLING HAMSTERS; REASSORTANT VIRUS; INFLUENZA; EPITOPES; SEQUENCE; MUTANTS; INFANTS AB Cold passage 18 (CP18) parainfluenza virus type 3 (PIV-3) vaccine was evaluated in a double-blind, randomized, placebo-controlled study of 95 infants and young children. None of 19 seropositive older children 41 to 124 months old became infected when 10(6) 50% tissue culture infective doses (TCID50) of vaccine virus was administered intranasally. Two of nine and seven of twenty-four young seropositive children given 10(5) or 10(6) TCID50 of CP18 PIV-3, respectively, became infected. Each of four seronegative young children became infected, as indicated by virus shedding and antibody response, when given 10(6) TCID50 of CP18 PIV-3 intranasally. Illness was not observed in seropositive children. Two of the four seronegative children developed a mild illness characterized by rhinorrhea and wheezing on auscultation; none had fever. In one case, vaccine virus spread from a vaccinee to a sibling control but did not cause illness. The vaccine is attenuated relative to wild-type PIV-3, but additional attenuation will be required to achieve a satisfactory PIV-3 vaccine. C1 ST LOUIS UNIV,SCH MED,DEPT PEDIAT,ST LOUIS,MO 63104. ST LOUIS VET ADM MED CTR,ST LOUIS,MO 63104. JOHNS HOPKINS UNIV,CTR IMMUNIZAT RES,BALTIMORE,MD 21205. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. RP BELSHE, RB (reprint author), ST LOUIS UNIV,SCH MED,DEPT INTERNAL MED,DIV INFECT DIS,CTR VACCINE DEV,ST LOUIS,MO 63104, USA. FU NIAID NIH HHS [N01-AI-05051, N01-AI-15095] NR 24 TC 37 Z9 37 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 AUG PY 1992 VL 30 IS 8 BP 2064 EP 2070 PG 7 WC Microbiology SC Microbiology GA JD594 UT WOS:A1992JD59400030 PM 1323576 ER PT J AU LI, FP FRAUMENI, JF AF LI, FP FRAUMENI, JF TI PREDICTIVE TESTING FOR INHERITED MUTATIONS IN CANCER-SUSCEPTIBILITY GENES SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID HUMAN GENOME PROJECT; LI-FRAUMENI SYNDROME C1 HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. NCI,BETHESDA,MD 20892. RP LI, FP (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 13 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG PY 1992 VL 10 IS 8 BP 1203 EP 1204 PG 2 WC Oncology SC Oncology GA JF661 UT WOS:A1992JF66100001 PM 1634911 ER PT J AU ODWYER, PJ LACRETA, FP SCHILDER, R NASH, S MCALEER, C MILLER, LL HUDES, GR OZOLS, RF AF ODWYER, PJ LACRETA, FP SCHILDER, R NASH, S MCALEER, C MILLER, LL HUDES, GR OZOLS, RF TI PHASE-I TRIAL OF THIOTEPA IN COMBINATION WITH RECOMBINANT HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TUMOR NECROSIS FACTOR; MOLECULAR-CLONING; ADVANCED BREAST; CANCER-PATIENTS; OVARIAN-CANCER; GM-CSF; CHEMOTHERAPY; MYELOSUPPRESSION; METABOLISM; TOXICITY C1 NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,INVEST DRUG BRANCH,BETHESDA,MD 20892. RP ODWYER, PJ (reprint author), FOX CHASE CANC INST,7701 BURHOLME AVE,PHILADELPHIA,PA 19111, USA. FU NCI NIH HHS [CA 06927] NR 40 TC 27 Z9 27 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 AUG PY 1992 VL 10 IS 8 BP 1352 EP 1358 PG 7 WC Oncology SC Oncology GA JF661 UT WOS:A1992JF66100022 PM 1634926 ER PT J AU ADAMSON, PC BALIS, FM MCCULLY, CL GODWIN, KS POPLACK, DG AF ADAMSON, PC BALIS, FM MCCULLY, CL GODWIN, KS POPLACK, DG TI METHOTREXATE PHARMACOKINETICS FOLLOWING ADMINISTRATION OF RECOMBINANT CARBOXYPEPTIDASE-G(2) IN RHESUS-MONKEYS SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HIGH-DOSE METHOTREXATE; LEUCOVORIN RESCUE; CLINICAL-TRIAL; CANCER RP ADAMSON, PC (reprint author), NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 29 TC 32 Z9 33 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG PY 1992 VL 10 IS 8 BP 1359 EP 1364 PG 6 WC Oncology SC Oncology GA JF661 UT WOS:A1992JF66100023 PM 1634927 ER PT J AU WEBER, J ROSENBERG, SA AF WEBER, J ROSENBERG, SA TI INTERLEUKIN-2 THERAPY WITH OR WITHOUT LYMPHOKINE-ACTIVATED KILLER-CELL INFUSIONS FOR LOW-GRADE NON-HODGKINS-LYMPHOMAS - REPLY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter RP WEBER, J (reprint author), NCI,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG PY 1992 VL 10 IS 8 BP 1366 EP 1366 PG 1 WC Oncology SC Oncology GA JF661 UT WOS:A1992JF66100027 ER PT J AU LONGO, DL DUFFEY, PL HUBBARD, SM YOUNG, RC DEVITA, VT AF LONGO, DL DUFFEY, PL HUBBARD, SM YOUNG, RC DEVITA, VT TI RADIATION-THERAPY IS BETTER THAN CHEMOTHERAPY IN EARLY-STAGE HODGKINS-DISEASE - NOT SO FAST SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 FOX CHASE CANC INST,PHILADELPHIA,PA 19111. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. RP LONGO, DL (reprint author), NCI,FREDERICK,MD 21701, USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG PY 1992 VL 10 IS 8 BP 1367 EP 1369 PG 3 WC Oncology SC Oncology GA JF661 UT WOS:A1992JF66100030 PM 1634930 ER PT J AU KORN, EL SIMON, R FRIEDMAN, MA MOORE, TD AF KORN, EL SIMON, R FRIEDMAN, MA MOORE, TD TI PHASE-II TRIALS OF SMALL-CELL LUNG-CANCER SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 MED ONCOL ASSOCIATES,PITTSBURGH,PA. RP KORN, EL (reprint author), NCI,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG PY 1992 VL 10 IS 8 BP 1369 EP 1370 PG 2 WC Oncology SC Oncology GA JF661 UT WOS:A1992JF66100032 PM 1321895 ER PT J AU HAIGLER, HJ KOSLOW, SH AF HAIGLER, HJ KOSLOW, SH TI NATIONAL-INSTITUTE-OF-MENTAL-HEALTH - PSYCHOTHERAPEUTIC MEDICATIONS DEVELOPMENT PROGRAM SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Editorial Material RP HAIGLER, HJ (reprint author), NIMH,ALCOHOL DRUG ABUSE & MENTAL HLTH ADM,DIV BASIC BRAIN & BEHAV SCI,ROCKVILLE,MD 20857, USA. NR 11 TC 2 Z9 2 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 AUG PY 1992 VL 12 IS 4 BP 231 EP 233 PG 3 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA JF318 UT WOS:A1992JF31800001 PM 1527224 ER PT J AU KETTER, TA PAZZAGLIA, PJ POST, RM AF KETTER, TA PAZZAGLIA, PJ POST, RM TI SYNERGY OF CARBAMAZEPINE AND VALPROIC ACID IN AFFECTIVE-ILLNESS - CASE-REPORT AND REVIEW OF THE LITERATURE SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Note ID CEREBRAL GLUCOSE-METABOLISM; COMPLEX PARTIAL SEIZURES; SODIUM VALPROATE; SERUM CONCENTRATIONS; THERAPY; EPOXIDE AB Carbamazepine and valproic acid are anticonvulsants with mood-stabilizing properties. Basic and clinical research suggest that these medications used together may have synergistic anticonvulsant effects. Psychotropic synergy of the combination has yet to be explored systematically. We present the case of a patient with rapid-cycling bipolar disorder studied under double-blind conditions whose hypomanias and depressions were refractory to either carbamazepine or valproic acid alone, but responded dramatically to the combination. The superior response to the combination appeared to be due to pharmacodynamic rather than pharmacokinetic effects. The clinical and theoretical aspects of the use of carbamazepine and valproic acid in combination are discussed. C1 NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 42 TC 62 Z9 62 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 AUG PY 1992 VL 12 IS 4 BP 276 EP 281 PG 6 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA JF318 UT WOS:A1992JF31800010 PM 1527232 ER PT J AU BLACK, B UHDE, TW TANCER, ME AF BLACK, B UHDE, TW TANCER, ME TI FLUOXETINE FOR THE TREATMENT OF SOCIAL PHOBIA SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Letter C1 UNIV N CAROLINA,DEPT PSYCHIAT,CHAPEL HILL,NC 27514. RP BLACK, B (reprint author), NIMH,BIOL PSYCHIAT BRANCH,ANXIETY & AFFECT DISORDERS SECT,BETHESDA,MD 20892, USA. NR 6 TC 109 Z9 109 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 AUG PY 1992 VL 12 IS 4 BP 293 EP 295 PG 3 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA JF318 UT WOS:A1992JF31800013 PM 1527235 ER PT J AU GORDON, CT AF GORDON, CT TI FUNDAMENTALS OF CHILD AND ADOLESCENT PSYCHOPATHOLOGY - HUSAIN,S, CANTWELL,D SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Book Review RP GORDON, CT (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD AUG PY 1992 VL 13 IS 4 BP 312 EP 312 PG 1 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA JH137 UT WOS:A1992JH13700040 ER PT J AU ABE, R ISHIDA, Y YUI, K KATSUMATA, M CHUSED, TM AF ABE, R ISHIDA, Y YUI, K KATSUMATA, M CHUSED, TM TI T-CELL RECEPTOR MEDIATED RECOGNITION OF SELF-LIGAND INDUCES SIGNALING IN IMMATURE THYMOCYTES BEFORE NEGATIVE SELECTION SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ANTIGEN RECEPTOR; MONOCLONAL-ANTIBODIES; MLS DETERMINANTS; LYMPHOCYTES-T; TOLERANCE; GENE; EXPRESSION; ACTIVATION; MOLECULES; PRODUCTS AB Shaping of the T cell repertoire by selection during intrathymic maturation involves T cell receptor (TCR) recognition of major histocompatibility complex/self-antigen complexes. In this communication, we studied the ability of minor lymphocyte stimulating (Mls) determinants to act as self-tolerogens in the selection of the T cell repertoire. We demonstrate that unprimed T cells from normal as well as TCR transgenic mice form Mls-specific conjugates with antigen-presenting cells, and that this TCR-ligand interaction leads to elevation of intercellular Ca2+ ([Ca2+]i). Peripheral T cells from TCR transgenic mice expressing receptors specific for self-Mls antigen show no reactivities to Mls(a). However, a proportion of immature thymocytes from these mice show specific binding and strong [Ca2+]i elevation in response to self-antigen-presenting cells, although these thymocytes do not proliferate. This self-reactivity of thymocytes is inhibited by antibodies specific for TCR, CD4, CD8, class II molecules, lymphocyte function-associated antigen 1, and intercellular adhesion molecule 1. These results demonstrate for the first time that before thymic negative selection, immature T cells can specifically interact with cells bearing self-antigen, and suggest that the resulting TCR-dependent signal transduction events provide a basis for negative selection of self-reactive T cells. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NIAID,IMMUNOL LAB,ROCKVILLE,MD 20852. UNIV PENN,DEPT PATHOL,PHILADELPHIA,PA 19104. UNIV PENN,MED LAB,PHILADELPHIA,PA 19104. RP ABE, R (reprint author), USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,MAIL STOP 44,BETHESDA,MD 20899, USA. NR 34 TC 16 Z9 16 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 1 PY 1992 VL 176 IS 2 BP 459 EP 468 DI 10.1084/jem.176.2.459 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA JF803 UT WOS:A1992JF80300015 PM 1500856 ER PT J AU TAKIZAWA, F ADAMCZEWSKI, M KINET, JP AF TAKIZAWA, F ADAMCZEWSKI, M KINET, JP TI IDENTIFICATION OF THE LOW AFFINITY RECEPTOR FOR IMMUNOGLOBULIN-E ON MOUSE MAST-CELLS AND MACROPHAGES AS FC-GAMMA-RII AND FC-GAMMA-RIII SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; IGE; BINDING; EXPRESSION; ANTIBODY; ANTIGEN; HETEROGENEITY; LYMPHOCYTES; SPECIFICITY; MAC-2 AB In addition to their well characterized high affinity immunoglobulin E (IgE) receptors (Fc-epsilon-RI) mast cells have long been suspected to express undefined Fc receptors capable of binding IgE with low affinity. In this paper, we show that Fc-gamma-RII and Fc-gamma-RIII, but not Mac-2, on mouse mast cells and macrophages bind IgE-immune complexes. This binding is efficiently competed by 2.4G2, a monoclonal antibody against the extracellular homologous region of both Fc-gamma-RII and Fc-gamma-RIII. Furthermore, IgE-immune complexes bind specifically to Fc-gamma-RII or Fc-gamma-RIII transfected into COS-7 cells. The association constants of IgE binding estimated from competition experiments are about 3.1 x 10(5) M-1 for Fc-gamma-RII, and 4.8 x 10(5) M-1 for Fc-gamma-RIII. Engagement of Fc-gamma-RII and Fc-gamma-RIII with IgE-immune complexes (after blocking access to Fc-epsilon-RI) or with IgG-immune complexes triggers C57.1 mouse mast cells to release serotonin. This release is inhibited by 2.4G2, and at maximum, reaches 30-40% of the intracellular content, about half of the maximal release (60-80%) obtained after Fc-epsilon-RI engagement. These data demonstrate that mouse Fc-gamma-RII and Fc-gamma-RIII are not isotype specific, and that the binding of IgE-immune complexes to these receptors induces cell activation. RP TAKIZAWA, F (reprint author), NIAID,MOLEC ALLERGY & IMMUNOL SECT,TWINBROOK II,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. NR 40 TC 120 Z9 121 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 1 PY 1992 VL 176 IS 2 BP 469 EP 476 DI 10.1084/jem.176.2.469 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA JF803 UT WOS:A1992JF80300016 PM 1386873 ER PT J AU ROZANOV, MN KOONIN, EV GORBALENYA, AE AF ROZANOV, MN KOONIN, EV GORBALENYA, AE TI CONSERVATION OF THE PUTATIVE METHYLTRANSFERASE DOMAIN - A HALLMARK OF THE SINDBIS-LIKE SUPERGROUP OF POSITIVE-STRAND RNA VIRUSES SO JOURNAL OF GENERAL VIROLOGY LA English DT Note ID NUCLEOTIDE-SEQUENCE; NONSTRUCTURAL PROTEINS; PLANT-VIRUSES; GENOMIC RNA; NSP1; EXPRESSION; REPLICATION; ACID AB Computer-assisted comparisons of the large proteins involved in the replication of viral RNA have revealed a novel domain located near the N termini of these proteins and conserved throughout the so-called 'Sindbis-like' supergroup of positive-strand RNA viruses. This domain encompasses four distinct conserved motifs, with motifs I, II and IV containing an invariant His residue, the AspXXArg signature and an invariant Tyr residue, respectively. Each of the two large groups of viruses within this supergroup, the 'altovirus' group (alphaviruses, tobamoviruses, tobraviruses, hordeiviruses, tricornaviruses, furoviruses, hepatitis E virus and probably rubiviruses), and the 'typovirus' group (tymoviruses, potexviruses, carlaviruses and apple chlorotic leaf spot virus), can be characterized by additional conserved sequence motifs. Based on the available results of biochemical studies and site-directed mutagenesis of the alphavirus proteins, it is hypothesized that this domain may be involved in methylation of the cap during viral RNA maturation. Unlike the other conserved domains, the RNA-dependent RNA polymerase and the RNA helicase, the motifs typical of the putative methyltransferase domain are universal within the Sindbis-like supergroup but are not found in the proteins of any other viruses, constituting a distinctive hallmark of this supergroup. C1 NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. RUSSIAN ACAD MED SCI,INST POLIOMYELITIS & VIRAL ENCEPHALITIDES,MOSCOW,USSR. INST JAQUES MONOD,2 PLACE JUSSIEU,F-75251 PARIS 05,FRANCE. RP ROZANOV, MN (reprint author), RUSSIAN ACAD SCI,INST MOLEC BIOL,MOSCOW,USSR. RI Gorbalenya, Alexander/J-4818-2012 OI Gorbalenya, Alexander/0000-0002-4967-7341 NR 26 TC 279 Z9 284 U1 3 U2 12 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD AUG PY 1992 VL 73 BP 2129 EP 2134 DI 10.1099/0022-1317-73-8-2129 PN 8 PG 6 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA JG774 UT WOS:A1992JG77400031 PM 1645151 ER PT J AU CEMAN, S RUDERSDORF, R LONG, EO DEMARS, R AF CEMAN, S RUDERSDORF, R LONG, EO DEMARS, R TI MHC CLASS-II DELETION MUTANT EXPRESSES NORMAL LEVELS OF TRANSGENE ENCODED CLASS-II MOLECULES THAT HAVE ABNORMAL CONFORMATION AND IMPAIRED ANTIGEN PRESENTATION ABILITY SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; LYMPHOBLASTOID CELL-LINE; GENE-TRANSFER; HLA-DR; RAPID METHOD; REGION; PATHWAY; DETERMINANT; TRANSPORTER; MUTATIONS AB Successive transfers of HLA-DR alpha and beta genes restored expression of HLA-DR antigens to human B-lymphoblastoid cell line, LCL .174, from which all known expressible class II genes are deleted. While transferent cells displayed large amounts of DR on their surfaces, transgene-encoded DR3 molecules lacked a conformation-dependent epitope. DR1-restricted CTL lysis of DR1-expressing transferents pulsed with native influenza virus proteins was greatly reduced; the same cells were efficiently lysed in the presence of CTL-recognized influenza peptides. The properties of DR-expressing transferents of .174 suggest they are defective in producing peptides from exogenous proteins or in forming DR/peptide complexes. Comparison with other DR-expressing deletion mutants indicates that at least one gene in an approximately 230 kb DNA segment between the DQ1 and Ring 7 loci is needed for normal DR-mediated processing and presentation. Production of DR3 molecules having the conformation-dependent 16.23 epitope and efficient DR1-restricted presentation of influenza viral epitopes occurred in a B cell line that has a mutation specifically eliminating expression of the TAP1 transporter gene, which is in the approximately 230 kb interval and is needed for production of HLA class I/peptide complexes. C1 UNIV WISCONSIN,DEPT GENET,MADISON,WI 53706. NIAID,MOLEC IMMUNOL SECT,IMMUNOGENET LAB,ROCKVILLE,MD 20852. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 FU NIGMS NIH HHS [GM0713317]; PHS HHS [A115486] NR 57 TC 72 Z9 72 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 AUG 1 PY 1992 VL 149 IS 3 BP 754 EP 761 PG 8 WC Immunology SC Immunology GA JF474 UT WOS:A1992JF47400002 PM 1634767 ER PT J AU HIRSCH, F GERMANA, S GUSTAFSSON, K PRATT, K SACHS, DH LEGUERN, C AF HIRSCH, F GERMANA, S GUSTAFSSON, K PRATT, K SACHS, DH LEGUERN, C TI STRUCTURE AND EXPRESSION OF CLASS-II ALPHA-GENES IN MINIATURE SWINE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; HLA-DR; HEAVY-CHAIN; CDNA; ANTIGENS; POLYMORPHISM; HAPLOTYPE; SEQUENCE; CLONING; CELLS AB Two overlapping genomic clones corresponding to the swine DRA class II gene were isolated and characterized. Restriction mapping and partial sequence data of the exon-containing fragments allowed identification and orientation of the five exons encoding the alpha-chain. Two full length cDNA clones corresponding to the transcribed DRA gene from two different haplotypes of the swine MHC were sequenced. Nucleotide sequence alignments revealed that the two swine DRA cDNA were very similar and closely related to the human DRA equivalent. An additional glycosylation site, compared with those of human DRA, was found in the second external domain of the protein. Northern analyses showed that porcine DRA and DQA genes were the only two class II alpha-genes expressed in the spleen, despite the presence of DPA and DZA genes in the genome. In addition to transfected cells expressing homologous pairs of alpha and beta-chains from SLA-DR, stable transfectants expressing nonhomologous pairs of alpha and beta-chains from DR and DQ loci were obtained, suggesting that such associations may contribute to the functional heterogeneity of class II products. C1 MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,MGH-E,BLDG 149,13TH ST,BOSTON,MA 02129. NCI,IMMUNOL BRANCH,BETHESDA,MD 20892. NR 36 TC 46 Z9 52 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 AUG 1 PY 1992 VL 149 IS 3 BP 841 EP 846 PG 6 WC Immunology SC Immunology GA JF474 UT WOS:A1992JF47400014 PM 1634772 ER PT J AU NISHIKATA, H OLIVER, C MERGENHAGEN, SE SIRAGANIAN, RP AF NISHIKATA, H OLIVER, C MERGENHAGEN, SE SIRAGANIAN, RP TI THE RAT MAST-CELL ANTIGEN AD1 (HOMOLOG TO HUMAN CD63 OR MELANOMA ANTIGEN ME491) IS EXPRESSED IN OTHER CELLS IN CULTURE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; TUMOR-ASSOCIATED ANTIGEN; AFFINITY IGE RECEPTOR; MONOCLONAL-ANTIBODY; MOLECULAR-CLONING; TRANSFECTED CELLS; IMMUNOGLOBULIN-E; SURFACE EXPRESSION; PLATELET P24/CD9; FIXED TISSUE AB Previously we reported that the mAb AD1 recognized a heavily glycosylated 50- to 60-kDa protein (AD1 Ag) sterically close to the high-affinity IgE receptor on rat basophilic leukemia (RBL-2H3) cells. The N-terminal amino acid sequence of the AD1 Ag was nearly identical to that of human CD63 (melanoma-associated Ag ME491). In this study we cloned the cDNA of AD1 Ag from a rat basophilic leukemia 2H3 cDNA library. An open reading frame of 238 amino acids was identified that contained the N-terminal 43 amino acid sequence. No evidence of a signal peptide was found. However, four predominantly hydrophobic stretches of sequence were predicted to form membrane-spanning helices, and three putative N-glycosylation sites were identified. The AD1 Ag and CD63 were highly conserved between rat and human, suggesting that the sequence of this protein is important for its function. By immunostaining various rat tissues, the AD1 Ag was found localized to mast cells. However, it was located to lysosomes, secretory granules and the plasma membrane of RBL-2H3 cells and to lysosomes and plasma membrane of many other cultured cell lines. The AD1 Ag could be induced by placing cells in culture. Fibroblasts and hepatocytes freshly isolated from rat embryos stained very weakly for AD1 Ag; however, after 24 to 48 h in culture they were strongly positive. This increase in the expression of the AD1 Ag was accompanied by an increase in detectable RNA message. Therefore, AD1/ME491/CD63 Ag is a mast cell marker in tissue, but is also associated with other cells in culture. C1 NIDR,IMMUNOL LAB,BLDG 10 1N-106,BETHESDA,MD 20892. RI Wan, Daniel/F-4689-2010 NR 53 TC 48 Z9 49 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 1992 VL 149 IS 3 BP 862 EP 870 PG 9 WC Immunology SC Immunology GA JF474 UT WOS:A1992JF47400017 PM 1634775 ER PT J AU YE, ZS KINET, JP PAUL, WE AF YE, ZS KINET, JP PAUL, WE TI STRUCTURE OF THE GENE FOR THE ALPHA-CHAIN OF THE MOUSE HIGH-AFFINITY RECEPTOR FOR IGE (FC-EPSILON-RI) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNOGLOBULIN-E; MAST-CELLS; TRANSFECTED CELLS; EXPRESSION; SUBUNIT; PRODUCTS AB Full-length genomic clones for the alpha-chain of mouse Fc-epsilon-RI were isolated and the exon/intron structure of the gene determined. The gene consisted of 5 exons, of which the first and second comprised the 5' untranslated region and the leader sequence; the third and fourth, the extracellular domain; and the fifth, the transmembrane and cytosolic domains, plus the 3' untranslated region. The upstream region was highly homologous to that of the rat counterpart. Primer extension and RNase protection analyses revealed multiple transcription initiation sites, between 30 and 120 nucleotides 3' of the putative TATA box. Comparison with other Fc receptor genes (rat Fc-epsilon-RI, mouse Fc-gamma-RIII-alpha, human Fc-gamma-RIIIB and human Fc-gamma-RIIIA-alpha) revealed a high degree of gene organization conservation. C1 NIAID,IMMUNOL LAB,BLDG 10,ROOM 11N311,BETHESDA,MD 20892. NIAID,MOLEC ALLERGY & IMMUNOL SECT,BETHESDA,MD 20892. NR 25 TC 17 Z9 17 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 AUG 1 PY 1992 VL 149 IS 3 BP 897 EP 900 PG 4 WC Immunology SC Immunology GA JF474 UT WOS:A1992JF47400021 PM 1386095 ER PT J AU CHIODETTI, L SCHWARTZ, RH AF CHIODETTI, L SCHWARTZ, RH TI INDUCTION OF COMPETENCE TO RESPOND TO IL-4 BY CD4+ T-HELPER TYPE-1 CELLS REQUIRES COSTIMULATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID STIMULATORY FACTOR-I; KINASE-C ACTIVATION; MONOCLONAL-ANTIBODY; LYMPHOCYTES-T; CYTOCHROME-C; AUTOCRINE GROWTH; B-CELLS; ANTIGEN; CLONES; INTERLEUKIN-4 AB Rested murine CD4+ Th1 clones do not produce IL-4, but have previously been shown to be capable of responding to IL-4 if they are first activated with Ag and APC. In this study, we have examined the activation requirements for induction of competence to respond to IL-4 in these clones. TCR occupancy alone (given either as chemically fixed APC and Ag, anti-CD3, Con A, or ionomycin and PMA) was inadequate, but the addition of a source of costimulation to any of these stimuli resulted in complete induction of competence to respond to IL-4. Pretreatment of the Th1 clones with TCR occupancy alone induced an anergic state from which subsequent full stimulation with Ag and APC failed to give IL-4 responsiveness. Pretreatment of the cells with IL-2 alone was an inadequate signal to induce IL-4 responsiveness and only a partial response was obtained when TCR occupancy was combined with IL-2. Addition of anti-IL-2 and anti-IL-2R antibodies during full activation with APC and Ag gave a 50% inhibition of competence induction. These results demonstrate that costimulation, in addition to its role in IL-2 production, is an important second signal for inducing T cells to become competent to respond to IL-4. RP CHIODETTI, L (reprint author), NIAID,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 51 TC 28 Z9 28 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 AUG 1 PY 1992 VL 149 IS 3 BP 901 EP 910 PG 10 WC Immunology SC Immunology GA JF474 UT WOS:A1992JF47400022 PM 1353098 ER PT J AU LOEFFLER, CM SMYTH, MJ LONGO, DL KOPP, WC HARVEY, LK TRIBBLE, HR TASE, JE URBA, WJ LEONARD, AS YOUNG, HA OCHOA, AC AF LOEFFLER, CM SMYTH, MJ LONGO, DL KOPP, WC HARVEY, LK TRIBBLE, HR TASE, JE URBA, WJ LEONARD, AS YOUNG, HA OCHOA, AC TI IMMUNOREGULATION IN CANCER-BEARING HOSTS - DOWN-REGULATION OF GENE-EXPRESSION AND CYTOTOXIC FUNCTION IN CD8+ T-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; ACTIVATED KILLER-CELLS; RECOMBINANT INTERLEUKIN-2; IMMUNE-RESPONSE; CYTO-TOXICITY; CYCLOPHOSPHAMIDE; IMMUNOTHERAPY; MELANOMA; ANTIGENS; MICE AB The causes of the decreased immune responsiveness in tumor-bearing hosts are incompletely understood. The impact of a decreased immune response in cancer patients on the clinical response in immunotherapy trials has not been evaluated. The present report demonstrates a marked decrease in the therapeutic efficacy of adoptively transferred T lymphocytes obtained from murine hosts bearing tumor for >30 days [late tumor-bearing mice (TBM)] as compared with normal mice and mice bearing tumor for <21 days (early TBM). In vitro analysis of the functions of the T lymphocytes from late TBM showed an apparently normal proliferative response to anti-CD3 and IL-2 with adequate lymphokine production from CD4+ cells, but a significant decrease in the cytotoxic function of CD8+ cells. The decreased cytotoxicity was not because of cell-mediated suppression. The expression of granzyme B mRNA was significantly delayed and decreased in magnitude in CD8+ cells from late TBM. Culture supernatants from two unrelated tumor cell lines were able to inhibit the cytotoxic activity of normal CD8+ cells in vitro. The tumor-derived suppressive factor is not transforming growth factor-beta (TGF-beta), but it has not been further characterized. The data suggest that one potential mechanism responsible for immunologic defects in patients with large tumor burdens is a tumor-induced defect that compromises the function of CD8+ effector T cells. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,POB B,FREDERICK,MD 21702. PROGRAM RESOURCES INC DYNCORP,IMMUNOTHERAPY LAB,CLIN SERV PROGRAM,FREDERICK,MD 21702. UNIV MINNESOTA,DEPT SURG,MINNEAPOLIS,MN 55455. RI Smyth, Mark/H-8709-2014 OI Smyth, Mark/0000-0001-7098-7240 FU NCI NIH HHS [N01-CO-74102] NR 37 TC 113 Z9 114 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 AUG 1 PY 1992 VL 149 IS 3 BP 949 EP 956 PG 8 WC Immunology SC Immunology GA JF474 UT WOS:A1992JF47400028 PM 1353099 ER PT J AU SEDEGAH, M SIM, BKL MASON, C NUTMAN, T MALIK, A ROBERTS, C JOHNSON, A OCHOLA, J KOECH, D WERE, B HOFFMAN, SL AF SEDEGAH, M SIM, BKL MASON, C NUTMAN, T MALIK, A ROBERTS, C JOHNSON, A OCHOLA, J KOECH, D WERE, B HOFFMAN, SL TI NATURALLY ACQUIRED CD8+ CYTOTOXIC LYMPHOCYTES-T AGAINST THE PLASMODIUM-FALCIPARUM CIRCUMSPOROZOITE PROTEIN SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MALARIA SPOROZOITES; CS PROTEIN; CELLS; EPITOPE; ANTIBODIES; PROTECTION; RECOGNIZE; GAMMA; CD4+ AB In rodent malaria model systems, protective immunity induced by immunization with irradiated sporozoites is eliminated by in vivo depletion of CD8+ T cells, and adoptive transfer of CTL clones against the circumsporozoite protein protects against malaria. We recently demonstrated that volunteers immunized with irradiated Plasmodium falciparum sporozoites produce CTL against peptide 368-390 of the P.falciparum circumsporozoite protein. To determine whether natural exposure to malaria induced similar CTL, we studied 11 adult, male, life-long residents of a highly malarious area of Kenya, who were selected because their lymphocytes had been shown to proliferate after stimulation with peptides 361-380, 371-390, or 368-390 and because nine had been resistant to malaria in previous studies. In four of the 11 individuals there was peptide-specific, genetically restricted, CTL activity. In all four individuals, this activity was unaffected by depletion of CD4+ T cells. In three volunteers the activity was eliminated or reduced by depletion of CD8+ T cells; in the fourth volunteer the CD8+ T cell depletion was uninterpretable. This first demonstration of CD8+ T cell, genetically restricted, Ag-specific CTL against a malaria protein among individuals exposed to endemic malaria provides a foundation for studying the relationship between circulating CTL and resistance to malaria infection. C1 USN,MED RES INST,DEPT DEF,MALARIA VACCINE PROGRAM,BETHESDA,MD 20889. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. PAN AMER HLTH ORG,WASHINGTON,DC 20037. USA,MED RES UNIT KENYA,NEW YORK,NY 09675. GEORGETOWN UNIV,DEPT PEDIAT,WASHINGTON,DC 20007. KENYA GOVT MED RES CTR,NAIROBI,KENYA. NIH,PARASIT DIS LAB,BETHESDA,MD 20892. OI MASON, CARL/0000-0002-3676-2811 NR 23 TC 61 Z9 61 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 AUG 1 PY 1992 VL 149 IS 3 BP 966 EP 971 PG 6 WC Immunology SC Immunology GA JF474 UT WOS:A1992JF47400030 PM 1634778 ER PT J AU YAMADA, K JELSEMA, CL BEAVEN, MA AF YAMADA, K JELSEMA, CL BEAVEN, MA TI CERTAIN INHIBITORS OF PROTEIN SERINE THREONINE KINASES ALSO INHIBIT TYROSINE PHOSPHORYLATION OF PHOSPHOLIPASE-C-GAMMA-1 AND OTHER PROTEINS AND REVEAL DISTINCT ROLES FOR TYROSINE KINASE(S) AND PROTEIN-KINASE-C IN STIMULATED, RAT BASOPHILIC RBL-2H3 CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SIGNAL TRANSDUCTION; SELECTIVE INHIBITOR; HISTAMINE-RELEASE; MAST-CELLS; RECEPTOR; POTENT; ACTIVATION; ALPHA; DEXAMETHASONE; STAUROSPORINE AB Various inhibitors of phospholipases and serine/threonine kinases were used to determine whether activation of these enzymes was necessary for Ag-induced exocytosis in rat basophilic RBL-2H3 cells. Several inhibitors, however, inhibited events other than those intended in stimulated RBL-2H3 cells. Staurosporine and KT5926, inhibitors of protein kinase C and myosin L chain kinase, respectively, suppressed, in a dose-dependent manner, hydrolysis of inositol phospholipids, release of arachidonic acid, and exocytosis in cells stimulated with Ag or Ca2+-ionophore, A23187. Such generalized inhibition could also be induced in permeabilized cells with several peptide inhibitors of tyrosine kinases. All the above inhibitors suppressed Ag-induced tyrosine phosphorylation of several proteins, including phospholipase C-gamma-1, and this suppression correlated with the inhibition of hydrolysis of inositol phospholipids and exocytosis. Three inhibitors of protein kinase C, Ro31-7549, calphostin C, and a peptide inhibitor, did not inhibit the tyrosine phosphorylation of proteins but selectively blocked exocytosis, presumably, by inhibiting protein kinase C. Thus, both tyrosine phosphorylation of proteins and the activation of protein kinase C were necessary events for hydrolysis of inositol phospholipids and exocytosis. C1 NHLBI,CHEM PHARMACOL LAB,BLDG 10,ROOM 8N114,BETHESDA,MD 20892. NIAMSD,ARTHRIT BRANCH,BETHESDA,MD 20892. EISAI & CO LTD,DEPT BIOCHEM,TSUKUBA RES LABS,TSUKUBA,IBARAKI 30026,JAPAN. NR 33 TC 57 Z9 57 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 AUG 1 PY 1992 VL 149 IS 3 BP 1031 EP 1037 PG 7 WC Immunology SC Immunology GA JF474 UT WOS:A1992JF47400039 PM 1378861 ER PT J AU ROSENGARD, BR OJIKUTU, CA FISHBEIN, J KORTZ, EO SACHS, DH AF ROSENGARD, BR OJIKUTU, CA FISHBEIN, J KORTZ, EO SACHS, DH TI SELECTIVE BREEDING OF MINIATURE SWINE LEADS TO AN INCREASED RATE OF ACCEPTANCE OF MHC-IDENTICAL, BUT NOT OF CLASS-I-DISPARATE, RENAL-ALLOGRAFTS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; TRANSPLANTATION; ANTIGEN; RECOGNIZE; SURVIVAL AB Previous work from this laboratory demonstrated that tolerance to MHC-identical or class I-disparate renal allografts develops in approximately one third of miniature swine without exogenous immunosuppression. A back-cross study indicated that rejection of MHC-identical transplants due to minor Ag was controlled by one or possibly two non-MHC-linked, autosomal dominant Ir genes. According to this hypothesis, and assuming complete penetrance, graft acceptors would be homozygous recessive at the relevant Ir loci, as would their offspring. Alternatively, if the gene(s) were incompletely penetrant, then two acceptors could give rise to a rejector. However, a high rate of MHC-identical graft acceptance would still be expected in the offspring of acceptors even if the Ir gene(s) were incompletely penetrant. To test this hypothesis and to obtain a higher frequency of acceptor animals for studies of tolerance, a program of selective breeding of renal allograft acceptors was begun. In the present paper, we assess the effect of selective breeding on renal graft acceptance. The analysis indicates a marked increase in the rate of MHC-identical graft acceptance, from 27.3% (n = 24) for the earliest of the four chronologic subgroups assessed to 64.5% (n = 33) for the most recent subgroup (p < 0.0001). Calculations of kinship revealed that the increased acceptance of MHC-identical grafts was not the result of differences between acceptors and rejectors in donor/recipient consanguinity. Class I-disparate grafts (n = 128) were similarly stratified chronologically and compared. Unlike MHC-identical grafts, the rate of acceptance of class I-disparate grafts has not changed over time. We conclude that rejector/acceptor status with respect to class I MHC incompatibility is determined by genetic factors in addition to those that control responses to minor antigen incompatibilities only. C1 MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,BLDG 149,13TH ST,BOSTON,MA 02129. NCI,IMMUNOL BRANCH,TRANSPLANTAT BIOL SECT,BETHESDA,MD 20892. FU NIAID NIH HHS [1 R01 AI 31046-01] NR 16 TC 19 Z9 19 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 AUG 1 PY 1992 VL 149 IS 3 BP 1099 EP 1103 PG 5 WC Immunology SC Immunology GA JF474 UT WOS:A1992JF47400048 PM 1634765 ER PT J AU SANDA, MG BOLTON, E MULE, JJ ROSENBERG, SA AF SANDA, MG BOLTON, E MULE, JJ ROSENBERG, SA TI INVIVO ADMINISTRATION OF RECOMBINANT MACROPHAGE COLONY-STIMULATING FACTOR INDUCES MACROPHAGE-MEDIATED ANTIBODY-DEPENDENT CYTOTOXICITY OF TUMOR-CELLS SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE MACROPHAGE COLONY-STIMULATING FACTOR; ANTIBODY-DEPENDENT CYTOTOXICITY; ANTIBODY-CONJUGATED TUMOR CELLS ID MURINE MACROPHAGES; MOLECULAR-CLONING; HUMAN-MONOCYTES; GROWTH-FACTOR; FACTOR CSF-1; INDUCTION; MICE AB Macrophage colony-stimulating factor (M-CSF) has been previously shown to facilitate the in vitro survival and differentiation of mononuclear phagocytes. We assessed whether M-CSF administration in vivo could induce macrophages capable of killing tumor via an antibody-dependent mechanism. C57BL/6 mice were given intraperitoneal M-CSF, and peritoneal macrophages were assayed for their ability to kill fluorochrome-labeled R1.1 thymoma cells in vitro in the presence or absence of target-specific antibody. Two-color flow cytometry was used in measuring tumor ingestion by macrophages; macrophages from M-CSF-treated mice eliminated >90% of R1.1 thymoma target within 24 hours, while macrophages from saline-treated controls were ineffective. R1.1 tumor elimination by macrophages depended on the presence of target-specific antibody. These are the first studies that demonstrate the in vivo induction, by M-CSF, of macrophages directly capable of ingesting antibody-conjugated tumor cells. C1 NCI,SURG BRANCH,DIV CANC TREATMENT,BETHESDA,MD 20892. RI Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015 NR 15 TC 23 Z9 23 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 AUG PY 1992 VL 12 IS 2 BP 132 EP 137 DI 10.1097/00002371-199208000-00008 PG 6 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA JE836 UT WOS:A1992JE83600008 PM 1504054 ER PT J AU MADORE, HP CHRISTY, C PICHICHERO, M LONG, C PINCUS, P VOSEFSKY, D KAPIKIAN, AZ DOLIN, R AF MADORE, HP CHRISTY, C PICHICHERO, M LONG, C PINCUS, P VOSEFSKY, D KAPIKIAN, AZ DOLIN, R TI FIELD TRIAL OF RHESUS ROTAVIRUS OR HUMAN-RHESUS ROTAVIRUS REASSORTANT VACCINE OF VP7 SEROTYPE-3 OR SEROTYPE-1 SPECIFICITY IN INFANTS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PLAQUE-REDUCTION NEUTRALIZATION; YOUNG-CHILDREN; VENEZUELAN INFANTS; MONOCLONAL-ANTIBODIES; IMMUNOGENICITY; MMU-18006; EFFICACY; REACTOGENICITY; ANTIGENICITY; PROTECTION AB Orally administered live rhesus monkey rotavirus vaccine (RRV, VP7 serotype 3) and human-rhesus reassortant rotavirus vaccine (DxRRV, VP7 serotype 1) were evaluated in a placebo-controlled field trial of 223 infants 2-4 months old. Both vaccines were mildly reactogenic but were generally well tolerated in the 10 days after vaccination. RRV and DxRRV were immunogenic, inducing serum antibody responses in 78% and 71% of the vaccinees, respectively. Efficacy of RRV vaccine was 66% (P = .01) and of DxRRV vaccine 77% (P = .002) against rotavirus-associated illness in the first season after vaccination. Efficacy of RRV vaccine against rotavirus-associated illness over three rotavirus seasons was 51.2% (P = .045) and of DxRRV vaccine was 67.3% (P = .006). RRV vaccine provided heterotypic protection of 58.5% (P = .041) and DxRRV vaccine provided homotypic protection of 72.8% (P = .005) over three seasons against the predominant serotype 1 rotavirus. C1 NIAID,BETHESDA,MD 20892. UNIV ROCHESTER,SCH MED & DENT,DEPT PEDIAT INFECT DIS,ROCHESTER,NY 14642. RP MADORE, HP (reprint author), UNIV ROCHESTER,SCH MED & DENT,DEPT ADULT INFECT DIS,BOX 689,601 ELMWOOD AVE,ROCHESTER,NY 14642, USA. FU NCRR NIH HHS [RR-00044]; NIAID NIH HHS [AI-52577] NR 49 TC 51 Z9 51 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG PY 1992 VL 166 IS 2 BP 235 EP 243 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JE578 UT WOS:A1992JE57800002 PM 1321858 ER PT J AU GRAHAM, BS BELSHE, RB CLEMENTS, ML DOLIN, R COREY, L WRIGHT, PF GORSE, GJ MIDTHUN, K KEEFER, MC ROBERTS, NJ SCHWARTZ, DH AGOSTI, JM FERNIE, BF STABLEIN, DM MONTEFIORI, DC LAMBERT, JS HU, SL ESTERLITZ, JR LAWRENCE, DN KOFF, WC AF GRAHAM, BS BELSHE, RB CLEMENTS, ML DOLIN, R COREY, L WRIGHT, PF GORSE, GJ MIDTHUN, K KEEFER, MC ROBERTS, NJ SCHWARTZ, DH AGOSTI, JM FERNIE, BF STABLEIN, DM MONTEFIORI, DC LAMBERT, JS HU, SL ESTERLITZ, JR LAWRENCE, DN KOFF, WC TI VACCINATION OF VACCINIA-NAIVE ADULTS WITH HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GP160 RECOMBINANT VACCINIA VIRUS IN A BLINDED, CONTROLLED, RANDOMIZED CLINICAL-TRIAL SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HERPES-SIMPLEX VIRUS; TOXIC T-CELLS; ENVELOPE GLYCOPROTEINS; HEPATITIS-B; GENE; AIDS; EXPRESSION; CONSTRUCTION; IMMUNIZATION; CHIMPANZEES AB The safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) gp160 recombinant vaccinia virus (HIVAC-1e) vaccine was evaluated in vaccinia-naive, healthy adults at low risk for acquiring HIV-1 infection. Volunteers (n = 36) were randomized to receive HIVAC-1e or control vaccinia virus at two dosages by bifurcated needle puncture at 0 and 2 months; 12 HIVAC-1e and 6 control vaccinia virus recipients received either 10(6) or 10(7) pfu/mL at each inoculation. There was no significant difference in lesion size, level of viral replication, or systemic symptoms after vaccination with HIVAC-1e or control vaccinia virus. Of 22 HIVAC-1e recipients with lesion formation, 16 developed low-titer gp160-specific antibody responses detectable by Western blot. The peak response occurred between days 70 and 120 and was still detectable at day 365 in 9 of 18 vaccinees. gp 160-specific lymphoproliferative responses were detected in 5 of 10 vaccinees. Vaccination with HIVAC-1e was safe in vaccinia-naive, healthy adults and could induce both humoral and cell-mediated gp160 specific immune responses. C1 ST LOUIS UNIV,SCH MED,ST LOUIS,MO 63104. UNIV ROCHESTER,SCH MED & DENT,ROCHESTER,NY 14642. BRISTOL MYERS SQUIBB,PHARMACEUT RES INST,SEATTLE,WA. UNIV WASHINGTON,SCH MED,SEATTLE,WA 98195. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD 21218. GEORGETOWN UNIV,ROCKVILLE,MD. EMMES CORP,POTOMAC,MD. NIH,BETHESDA,MD 20892. RP GRAHAM, BS (reprint author), VANDERBILT UNIV,MED CTR,SCH MED,DEPT MED,DIV INFECT DIS,A-3310 MCN,NASHVILLE,TN 37232, USA. RI Hu, Shiu-Lok/A-3196-2008 OI Hu, Shiu-Lok/0000-0003-4336-7964 FU NIAID NIH HHS [AI-05062, AI-05061, AI-82500] NR 36 TC 120 Z9 121 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 AUG PY 1992 VL 166 IS 2 BP 244 EP 252 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JE578 UT WOS:A1992JE57800003 PM 1353102 ER PT J AU CERNY, A MERINO, R FOSSATI, L DEKOSSODO, S HEUSSER, C WALDVOGEL, FA MORSE, HC IZUI, S AF CERNY, A MERINO, R FOSSATI, L DEKOSSODO, S HEUSSER, C WALDVOGEL, FA MORSE, HC IZUI, S TI EFFECT OF CYCLOSPORINE-A AND ZIDOVUDINE ON IMMUNE ABNORMALITIES OBSERVED IN THE MURINE ACQUIRED-IMMUNODEFICIENCY-SYNDROME SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID T-CELL SUBSETS; INDUCTION; MICE; VIRUS; DISEASE; MAIDS; MODEL; EXPRESSION; ACTIVATION; PATHWAYS AB Two therapeutic modalities, zidovudine (targeting retroviral replication) and cyclosporin A (targeting immunopathologic consequences of retroviral expression) were evaluated in a murine model of AIDS. In previous studies, cyclosporin A treatment (40 or 60 mg/kg/day) before and after infection with LP-BM5 murine leukemia viruses protected against the development of immunodeficiency disease. The present study extends these findings. First, a low dose of cyclosporin A (20 mg/kg/day) was ineffective, and treatment initiated 5 days after infection did not protect against virus-induced lymphoproliferation and hypergammaglobulinemia. Second, zidovudine added to drinking water (0.1 mg initiated 5 days after infection and continued for 8 weeks) was more effective than 0.2 mg/mL given day 5-12 after infection. This treatment reduced lymph node size, disease severity as determined histologically, retrovirus-induced gp70 expression, and IgE (but not IgM and IgG) levels. Third, combined treatment had an additive, protective effect on lymphocyte proliferative capacity. This successful dual therapeutic strategy in a mouse model has potential applicability for similar approaches in treating human immunodeficiency virus infection. C1 UNIV GENEVA,HOP CANTONAL,DEPT MED,CH-1211 GENEVA 4,SWITZERLAND. UNIV GENEVA,HOP CANTONAL,DEPT PATHOL,CH-1211 GENEVA 4,SWITZERLAND. CIBA GEIGY AG,PRECLIN RES,CH-4002 BASEL,SWITZERLAND. NIAID,IMMUNOPATHOL LAB,BETHESDA,MD 20892. RI Merino, Ramon/L-1310-2014 OI Merino, Ramon/0000-0002-5306-0635 FU NIAID NIH HHS [AI-72622] NR 33 TC 11 Z9 11 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 AUG PY 1992 VL 166 IS 2 BP 285 EP 290 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JE578 UT WOS:A1992JE57800009 PM 1634800 ER PT J AU LEVINE, PH JAHAN, N MURARI, P MANAK, M JAFFE, ES AF LEVINE, PH JAHAN, N MURARI, P MANAK, M JAFFE, ES TI DETECTION OF HUMAN HERPESVIRUS-6 IN TISSUES INVOLVED BY SINUS HISTIOCYTOSIS WITH MASSIVE LYMPHADENOPATHY (ROSAI-DORFMAN DISEASE) SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID EPSTEIN-BARR-VIRUS; CELL LEUKEMIA LYMPHOMA; REED-STERNBERG CELLS; HODGKINS-DISEASE; LYMPHOPROLIFERATIVE DISORDERS; EXANTHEM SUBITUM; VIRAL GENOMES; INFECTION; HHV-6; IDENTIFICATION AB After preliminary serologic data demonstrated elevated antibody titers to human herpesvirus (HHV) 6 in patients with sinus histiocytosis with massive lymphadenopathy (SHML) or Rosai-Dorfman disease, tissues were examined from 9 patients with classical SHML to search for evidence of HHV-6 infection. Involved tissues from 7 of the 9 patients had detectable HHV-6 by in situ hybridization: Tissue from 1 had detectable Epstein-Barr virus genome but no HHV-6 and tissue from another had no detectable HHV-6 or Epstein-Barr virus. These studies suggest that HHV-6 and, to a lesser extent, Epstein-Barr virus may be involved in the etiology of SHML. C1 BIOTECH RES LABS INC,ROCKVILLE,MD. USAF,INST PATHOL,WASHINGTON,DC 20330. RP LEVINE, PH (reprint author), NCI,BLDG EPN,RM 434,BETHESDA,MD 20892, USA. OI Manak, Mark /0000-0002-9217-9129 FU NIAID NIH HHS [AI-82502] NR 41 TC 151 Z9 160 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG PY 1992 VL 166 IS 2 BP 291 EP 295 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JE578 UT WOS:A1992JE57800010 PM 1321861 ER PT J AU KONKEL, ME MEAD, DJ HAYES, SF CIEPLAK, W AF KONKEL, ME MEAD, DJ HAYES, SF CIEPLAK, W TI TRANSLOCATION OF CAMPYLOBACTER-JEJUNI ACROSS HUMAN POLARIZED EPITHELIAL-CELL MONOLAYER-CULTURES SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ESCHERICHIA-COLI; HEP-2 CELLS; INFECTION; SALMONELLA; MICE; COLONIZATION; ENTERITIS; CACO-2; IDENTIFICATION; ASSOCIATION AB The ability of Campylobacter jejuni isolates to translocate across an epithelial cell barrier was investigated by using polarized Caco-2 cell monolayers grown on microporous membrane filters. The 4 C.jejuni isolates tested all traversed the Caco-2 cell monolayers and displayed similar translocation kinetics. The number of bacteria crossing the polarized cell monolayers continued to increase with time until 4 h after inoculation, at which time a maximum rate of translocation was observed. Transmission electron microscopy revealed that C.jejuni translocated across polarized Caco-2 cell monolayers by passing both through and between cells. Chloramphenicol, an inhibitor of bacterial protein synthesis, reduced the translocation of C.jejuni. Bacterial attachment, internalization, and translocation were inhibited at low temperature. These data indicate that adherence, penetration, and translocation of C.jejuni require active bacterial and target cell processes and further suggest a role for cellular translocation in the pathogenesis of C.jejuni-mediated enteritis. C1 NIAID,HAMILTON,MT 59840. RP KONKEL, ME (reprint author), ROCKY MT LABS,VECTORS & PATHOGENS LAB,HAMILTON,MT 59840, USA. NR 49 TC 63 Z9 63 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG PY 1992 VL 166 IS 2 BP 308 EP 315 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JE578 UT WOS:A1992JE57800012 PM 1634802 ER PT J AU BOULOS, R RUFF, AJ NAHMIAS, A HOLT, E HARRISON, L MAGDER, L WIKTOR, SZ QUINN, TC MARGOLIS, H HALSEY, NA AF BOULOS, R RUFF, AJ NAHMIAS, A HOLT, E HARRISON, L MAGDER, L WIKTOR, SZ QUINN, TC MARGOLIS, H HALSEY, NA TI HERPES-SIMPLEX VIRUS TYPE-2 INFECTION, SYPHILIS, AND HEPATITIS-B VIRUS-INFECTION IN HAITIAN WOMEN WITH HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 AND HUMAN T-LYMPHOTROPIC VIRUS TYPE-I INFECTIONS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID SURFACE-ANTIGEN; TRANSMISSION; ANTIBODY; HIV-1; AIDS AB Antibodies to herpes simplex virus type 2 (HSV-2), antibodies to hepatitis B virus (HBV) core antigen (anti-HBc), and VDRL antibodies (serologic evidence of syphilis) were evaluated in women known to be infected with human immunodeficiency virus type 1 (HIV-1) (n = 95) or human T lymphotropic virus type I (HTLV-I)(n = 45) and controls (n = 89). HIV-1-seropositive women were more likely than controls to have antibodies to HSV-2 (88% vs. 54%; P < .001), anti-HBc (67% vs. 43%; P = .008), and VDRL antibodies (21% vs. 8%; P = .02). Similarly, HTLV-I-seropositive women were more likely than controls to have antibodies to HSV-2 (82% vs. 54%; P = .003) and anti-HBc (67% vs. 43%; P = .008). There was no evidence that HIV-1 or HTLV-I predisposed to chronic hepatitis B virus infection. The stronger associations between HIV-1 and HTLV-I with HSV-2 than the associations with syphilis or HBV are consistent with the hypothesis that recurrent disruptions of mucous membranes caused by HSV-2 infections predispose to sexual transmission of HIV-1 and HTLV-I. C1 JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, DEPT INT HLTH, 615 N WOLFE ST, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT MED, BALTIMORE, MD 21205 USA. NIAID, IMMUNOREGULAT LAB, BETHESDA, MD 20892 USA. NCI, BETHESDA, MD 20892 USA. EMORY UNIV, DEPT PEDIAT, ATLANTA, GA 30322 USA. CTR DIS CONTROL, CTR INFECT DIS, HEPATITIS BRANCH, ATLANTA, GA 30333 USA. FU NIAID NIH HHS [AI-26521] NR 15 TC 42 Z9 42 U1 0 U2 0 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 AUG PY 1992 VL 166 IS 2 BP 418 EP 420 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JE578 UT WOS:A1992JE57800027 PM 1321862 ER PT J AU SHINDO, M DIBISCEGLIE, AM BISWAS, R MIHALIK, K FEINSTONE, SM AF SHINDO, M DIBISCEGLIE, AM BISWAS, R MIHALIK, K FEINSTONE, SM TI HEPATITIS-C VIRUS-REPLICATION DURING ACUTE INFECTION IN THE CHIMPANZEE SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID NON-A AB The events following experimental infection of 2 chimpanzees with the H strain of hepatitis C virus (HCV) were studied by quantitating the levels of HCV RNA in liver and serum. Serum and liver samples were tested every 1-3 weeks for up to 32 weeks. The genomic and antigenomic strands of HCV RNA were individually detected in liver and serum by strand-specific reverse transcription followed by polymerase chain reaction (PCR) using nested primers specific for the 5' noncoding region of the HCV genome and were quantitated by end-point dilution of the nucleic acid extract. Both genomic and antigenomic strands were detected in liver and serum within 1 week after inoculation and approximately 1 week before the development of elevated levels of alanine aminotransferase (ALT) activity. Changes in levels of antigenomic strand paralleled those of the genomic strand in both serum and liver. Titers of HCV RNA in serum and liver generally correlated with changes in ALT levels. C1 US FDA,DIV TRANSFUS SCI,BETHESDA,MD 20014. US FDA,DIV VIROL,BETHESDA,MD 20014. US FDA,CTR BIOL EVOLUT & RES,BETHESDA,MD 20014. US FDA,HEPATITIS RES LAB,BETHESDA,MD 20014. RP SHINDO, M (reprint author), NIDDK,LIVER DIS SECT,BLDG 10,ROOM 4D52,BETHESDA,MD 20892, USA. NR 15 TC 61 Z9 62 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 AUG PY 1992 VL 166 IS 2 BP 424 EP 427 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JE578 UT WOS:A1992JE57800029 PM 1321863 ER PT J AU MEIER, JL STRAUS, SE AF MEIER, JL STRAUS, SE TI COMPARATIVE BIOLOGY OF LATENT VARICELLA-ZOSTER VIRUS AND HERPES-SIMPLEX VIRUS-INFECTIONS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Review ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; HUMAN TRIGEMINAL GANGLIA; CENTRAL NERVOUS-SYSTEM; IMMEDIATE-EARLY GENE; GENITAL HERPES; ELECTRON-MICROSCOPY; ACYCLOVIR THERAPY; TYPE-2 INFECTION; THORACIC GANGLIA; IMMUNE-RESPONSE AB The clinicoepidemiologic features of varicella-zoster virus and herpes simplex virus latency are clearly distinctive. These differences indicate that each virus has evolved a unique strategy to ensure the establishment and maintenance of latency and to reactivate therefrom. Indeed, current data reveal divergent pathogenetic and molecular biologic properties that may account for the clinicoepidemiologic characteristics that distinguish recurrent infections with these herpesviruses. C1 NIAID,CLIN INVEST LAB,MED VIROL SECT,BLDG 10,RM 11N228,BETHESDA,MD 20892. NR 105 TC 66 Z9 68 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG PY 1992 VL 166 SU 1 BP S13 EP S23 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JF561 UT WOS:A1992JF56100003 PM 1320646 ER PT J AU PUNNONEN, K YUSPA, SH AF PUNNONEN, K YUSPA, SH TI ULTRAVIOLET-LIGHT IRRADIATION INCREASES CELLULAR DIACYLGLYCEROL AND INDUCES TRANSLOCATION OF DIACYLGLYCEROL KINASE IN MURINE KERATINOCYTES SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID ORNITHINE DECARBOXYLASE ACTIVITY; HUMAN EPIDERMAL-KERATINOCYTES; INOSITOL LIPID-METABOLISM; RAS-TRANSFORMED CELLS; ARACHIDONIC-ACID; PHOSPHOLIPID-METABOLISM; TUMOR PROMOTION; DNA-SYNTHESIS; CD-1 MICE; PROTEIN AB Cellular lipid metabolism can provide a variety of mediators of signal transduction, including diacylglycerols and inositol phosphates. These factors may be involved in the control of epidermal differentiation and proliferation because they are modulated by extracellular calcium, which also regulates the maturation phenotype of cultured keratinocytes. The effect of non-cytotoxic exposures to ultraviolet light on lipid metabolism was studied in cultured murine keratinocytes. Ultraviolet treatment of cultured murine keratinocytes growing in 0.05 mM Ca++ did not significantly change the total amount o f [H-3]inositol phosphates at 0.5, 8, or 24 h post-irradiation. irradiated cells responded to an increase from 0.05 mM Ca++ to 1.4 mM Ca++ medium with increased formation of inositol phosphates suggesting irradiation did not alter the normal inositol lipid turnover in response to the Ca++ signal for terminal differentiation. Irradiation (20 - 120 J/m2 of UVB) induced a dose-dependent increase in the cellular level of diacylglycerols as measured at 24 h post-irradiation, without changing the turnover of other phospholipids including phosphatidylcholine and phosphatidylethanolamine. The increased cellular levels of diacylglycerols folloWing ultraviolet exposure were accompanied by changes in the activity of diacylglycerol kinase (DAG-kinase). The cytosolic DAG-kinase activity was decreased whereas the DAG-kinase activity in the membrane fraction was increased. These results suggest that ultraviolet irradiation increases the level of diacylglycerols via changes in de novo metabolism through a DAG-kinase pathway. Elevated diacylglycerol may influence signal-transduction pathways mediated by cellular lipids and contribute to some keratinocyte responses to ultraviolet light. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BLDG 37,ROOM 3B25,BETHESDA,MD 20892. NR 48 TC 45 Z9 46 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 1992 VL 99 IS 2 BP 221 EP 226 DI 10.1111/1523-1747.ep12650445 PG 6 WC Dermatology SC Dermatology GA JE699 UT WOS:A1992JE69900018 PM 1321202 ER PT J AU DHAWAN, S TORO, LA JONES, BE MELTZER, MS AF DHAWAN, S TORO, LA JONES, BE MELTZER, MS TI INTERACTIONS BETWEEN HIV-INFECTED MONOCYTES AND THE EXTRACELLULAR-MATRIX - HIV-INFECTED MONOCYTES SECRETE NEUTRAL METALLOPROTEASES THAT DEGRADE BASEMENT-MEMBRANE PROTEIN MATRICES SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Note DE BASEMENT MEMBRANE; EXTRACELLULAR MATRIX; METALLOPROTEASE; HIV-1 ID HUMAN MONONUCLEAR PHAGOCYTES; CELL TROPISM; AIDS VIRUS; MACROPHAGES; EXPRESSION; IDENTIFICATION; TISSUE AB The frequency of human immunodeficiency virus (HIV)-infected monocytes that spread on a model basement membrane was about twofold greater than that of an equal number of uninfected control cells through the initial 12 to 18 h of culture. By 24 h, virtually all HIV-infected and uninfected control cells spread on the basement membrane gel. The frequency of spread cells in the uninfected control population was < 10% of total cells by 12 days. In contrast, 30 to 40% of HIV-infected monocytes remained spread through this time interval and formed a dense interdigitated network of cell processes on and into the gel matrix. Invasion of the basement membrane matrix by HIV-infected monocytes suggested increased secretion of proteases able to digest the gel. Indeed, levels of neutral protease activity in culture fluids from HIV-infected monocytes were significantly higher than those from equal numbers of uninfected control cells. High levels of protease activity in culture fluids of HIV-infected monocytes required productive virus infection and were not observed with cells exposed to T cell-tropic HIV isolates. The predominant protease activity in these cultures was a 92-kd neutral metallogelatinase. HIV-induced changes in monocyte metalloprotease activity may be important for extravasation of infected cells to tissue or for the development of AIDS-associated neuropathology, carcinogenesis, and opportunistic infection. C1 WALTER REED ARMY MED CTR,DEPT CELLULAR IMMUNOL,DIV COMMUNICABLE DIS & IMMUNOL,WASHINGTON,DC 20307. NEI,BETHESDA,MD 20892. NR 23 TC 26 Z9 26 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD AUG PY 1992 VL 52 IS 2 BP 244 EP 248 PG 5 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA JQ370 UT WOS:A1992JQ37000017 PM 1506780 ER PT J AU GRZESIEK, S BAX, A AF GRZESIEK, S BAX, A TI AN EFFICIENT EXPERIMENT FOR SEQUENTIAL BACKBONE ASSIGNMENT OF MEDIUM-SIZED ISOTOPICALLY ENRICHED PROTEINS SO JOURNAL OF MAGNETIC RESONANCE LA English DT Note ID N-15 CHEMICAL-SHIFTS; TRIPLE-RESONANCE NMR; C-13; SPECTROSCOPY; CALMODULIN; H-1 RP GRZESIEK, S (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. NR 22 TC 365 Z9 368 U1 4 U2 23 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0022-2364 J9 J MAGN RESON JI J. Magn. Reson. PD AUG PY 1992 VL 99 IS 1 BP 201 EP 207 DI 10.1016/0022-2364(92)90169-8 PG 7 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA JH478 UT WOS:A1992JH47800019 ER PT J AU KULLER, L BENVENISTE, RE WATANABE, R TSAI, CC MORTON, WR AF KULLER, L BENVENISTE, RE WATANABE, R TSAI, CC MORTON, WR TI TRANSMISSION OF SIVMNE FROM FEMALE TO MALE MACACA-NEMESTRINA SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article DE MACAQUE; SIVMNE; HETEROSEXUAL; NATURAL TRANSMISSION; AIDS ID SIMIAN IMMUNODEFICIENCY VIRUS; HETEROSEXUAL TRANSMISSION; MOLECULAR CHARACTERIZATION; MACAQUES; INFECTION; PROTEINS; MEN; HIV; SEROCONVERSION; INOCULATION AB Three SIV(Mne)-infected female pigtailed macaques (Macaca nemestrina) were mated with two SIV-negative males. The females exhibited signs of SAIDS and SIV(Mne) was readily isolated from peripheral blood mononuclear cells (PBMC). Both males became infected with SIV(Mne), developed SAIDS, and died. This is the first documented case of the transmission of SIV(Mne) between adult macaques housed together. Although transmission through scratching or biting cannot be ruled out, heterosexual transmission appears the most likely mode of SIV(Mne) transmission in this study. C1 NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. RP KULLER, L (reprint author), UNIV WASHINGTON,REG PRIMATE RES CTR,1321 HSB,SJ-50,SEATTLE,WA 98195, USA. NR 31 TC 13 Z9 13 U1 1 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 AUG PY 1992 VL 21 IS 6 BP 299 EP 307 PG 9 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA KT162 UT WOS:A1992KT16200002 PM 1297851 ER PT J AU CHANDRAN, B TIRAWATNAPONG, S PFEIFFER, B ABLASHI, DV AF CHANDRAN, B TIRAWATNAPONG, S PFEIFFER, B ABLASHI, DV TI ANTIGENIC RELATIONSHIPS AMONG HUMAN HERPESVIRUS-6 ISOLATES SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE ANTIGENIC VARIATIONS; REACTIVITY OF HUMAN SERA; HHV-6 ID VIRUS HUMAN HERPESVIRUS-6; EXANTHEM SUBITUM; GROWTH-PROPERTIES; HHV-6; IDENTIFICATION; INFECTION; SALIVA; POLYMORPHISM; STRAINS; TROPISM AB Human herpesvirus 6 (HHV-6) prototype isolate GS is a newly identified lymphotropic herpesvirus and several subsequent herpes isolates were recognized as HHV-6 by their hybridization to a HHV-6(GS) DNA probe pZVH14. DNA restriction analysis and in vitro tropism studies show that HHV-6 isolates can be divided into two groups, designated group A and group B. Antigenic relationships among 15 HHV-6 isolates belonging to these two groups were examined using rabbit antibodies against HHV-6(GS) infected cells, 11 monoclonal antibodies against three glycoproteins and four non-glycoproteins of HHV-6(GS), and sera from 136 healthy adults. More than 20 polypeptides from all these isolates were immunoprecipitated by rabbit polyclonal antibodies against HHV-6(GS) infected cells. Reactivities monoclonal antibodies segregated these isolates into the same two groups. Group A contains HHV-6(GS), HHV-6(U1102) from a Ugandan acquired immunodeficiency syndrome (AIDS) patient, and nine other HHV-6 isolates from various disorders. HHV-6(Z-29) from a Zairian AIDS patient, HHV-6(SF) isolated from the saliva of a human immunodeficiency virus (HIV)-infected individual, HHV-6(OK) from a child with exanthem subitum, and HHV-6(DC) from a leukopenia patient are in group B. Eighty-one percent of the sera showed similar antibody titer in immunofluorescence assay with group A HHV-6(GS) and group B HHV-6(Z-29) infected cells and 19% of the sera showed two- to four-fold antibody titer differences. The mobilities of many of the polypeptides immunoprecipitated from group A HHV-6(GS) and group B HHV-6(Z-29) infected cells were different and sera showed differences in the quantities and nature of polypeptides immunoprecipitated. Together, our data show that HHV-6 related isolates segregate into two antigenically closely related yet distinct groups, exhibiting group common and group specific antigenic epitopes. The complex patterns of reactivities of human sera suggest that individuals may be infected with viruses from one group or both groups. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP CHANDRAN, B (reprint author), UNIV KANSAS,MED CTR,DEPT MICROBIOL MOLEC GENET & IMMUNOL,KANSAS CITY,KS 66103, USA. FU NIAID NIH HHS [AI 30355, AI 24224, AI 322109] NR 34 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 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD AUG PY 1992 VL 37 IS 4 BP 247 EP 254 DI 10.1002/jmv.1890370403 PG 8 WC Virology SC Virology GA JG922 UT WOS:A1992JG92200002 PM 1328500 ER PT J AU TABOR, E FARSHID, M DIBISCEGLIE, A HSIA, CC AF TABOR, E FARSHID, M DIBISCEGLIE, A HSIA, CC TI INCREASED EXPRESSION OF TRANSFORMING GROWTH FACTOR-ALPHA AFTER TRANSFECTION OF A HUMAN HEPATOBLASTOMA CELL-LINE WITH THE HEPATITIS-B VIRUS SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE GROWTH FACTOR; HEPATOCARCINOGENESIS; HEPATOCELLULAR CARCINOMA AB The expression of transforming growth factor-alpha (TGF-alpha) was examined in a human hepatoblastoma cell line, Hep G2, which does not contain hepatitis B virus (HBV) DNA, and in the cell line 2.2.15, which was formed by the transfection of Hep G2 cells with the complete HBV DNA, to study the possibility that HBV and TGF-alpha could function as co-factors in hepatocarcinogenesis. Northern blot hybridization of RNA extracted from these cell lines, with densitometric analysis, revealed expression of the TGF-alpha gene in the transfected cells at a level three times higher than in the nontransfected cells. Staining of the cells using a monoclonal antibody to TGF-alpha and the avidin-biotin-peroxidase immunohistochemical method revealed a much higher intensity of TGF-alpha staining in the transfected cell line. These findings show that the presence of HBV DNA appears to cause a significant up-regulation of the TGF-alpha gene. This effect on the TGF-alpha gene may be a mechanism by which HBV contributes to the etiology of hepatocellular carcinoma in some patients. C1 NIDDKD, BETHESDA, MD USA. RP TABOR, E (reprint author), NCI, BETHESDA, MD 20892 USA. NR 6 TC 17 Z9 17 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD AUG PY 1992 VL 37 IS 4 BP 271 EP 273 DI 10.1002/jmv.1890370406 PG 3 WC Virology SC Virology GA JG922 UT WOS:A1992JG92200005 PM 1328501 ER PT J AU IWAMOTO, H PODOLSKY, RJ AF IWAMOTO, H PODOLSKY, RJ TI LIGAND-DEPENDENT ROTATION OF MYOSIN HEAD CROSS-LINKED TO ACTIN WITH EDC IN SKINNED RABBIT SKELETAL-MUSCLE FIBERS SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Meeting Abstract C1 NIAMS,PHYS BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PD AUG PY 1992 VL 13 IS 4 BP 476 EP 477 PG 2 WC Cell Biology SC Cell Biology GA JG764 UT WOS:A1992JG76400015 ER PT J AU HILTON, BD CHMURNY, GN MUSCHIK, GM AF HILTON, BD CHMURNY, GN MUSCHIK, GM TI TAXOL - QUANTITATIVE INTERNUCLEAR PROTON-PROTON DISTANCES IN CDCL3 SOLUTION FROM NOE DATA - 2D NMR ROESY BUILDUP RATES AT 500 MHZ SO JOURNAL OF NATURAL PRODUCTS LA English DT Note ID TWO-DIMENSIONAL NMR; CROSS-RELAXATION; SPECTROSCOPY AB Quantitative nmr internuclear proton-proton distance measurements obtained by observation of the initial buildup rates of nOe's in 2D ROESY spectra of taxol [1) in CDCl3 are reported. A comparison to the X-ray crystal structure of taxotere [2] is made, and the results are discussed in terms of previous studies of structure-activity relationships. RP HILTON, BD (reprint author), NCI,FREEDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,DYNCORP,POB B,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 15 TC 35 Z9 35 U1 1 U2 3 PU AMER SOC PHARMACOGNOSY PI CINCINNATI PA LLOYD LIBRARY & MUSEUM 917 PLUM ST, CINCINNATI, OH 45202 SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD AUG PY 1992 VL 55 IS 8 BP 1157 EP 1161 DI 10.1021/np50086a023 PG 5 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA JJ008 UT WOS:A1992JJ00800023 PM 1359020 ER PT J AU KNUSEL, B KAPLAN, DR WINSLOW, JW ROSENTHAL, A BURTON, LE BECK, KD RABIN, S NIKOLICS, K HEFTI, F AF KNUSEL, B KAPLAN, DR WINSLOW, JW ROSENTHAL, A BURTON, LE BECK, KD RABIN, S NIKOLICS, K HEFTI, F TI K-252B SELECTIVELY POTENTIATES CELLULAR ACTIONS AND TRK TYROSINE PHOSPHORYLATION MEDIATED BY NEUROTROPHIN-3 SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE ALZHEIMERS DISEASE; BRAIN-DERIVED NEUROTROPHIC FACTOR; NERVE GROWTH FACTOR RECEPTOR; NEUROTROPHIN-3; PROTEIN KINASE INHIBITORS; PARKINSONS DISEASE ID NERVE GROWTH-FACTOR; SEPTAL CHOLINERGIC NEURONS; PROTEIN-KINASE INHIBITOR; MOLECULAR-CLONING; PC12 CELLS; FACTOR FAMILY; FACTOR RECEPTOR; GENE-TRANSFER; BRAIN; SURVIVAL AB K-252b, a protein kinase inhibitor, has been shown earlier to inhibit nerve growth factor actions on cholinergic neurons of the basal forebrain. In the present study, K-252b was found to prevent trophic actions of two other neurotrophins, brain-derived neurotrophic factor, and neurotrophin-3, on central cholinergic and dopaminergic neurons, peripheral sensory neurons, and PC12 pheochromocytoma cells, when used at >2-mu-M concentration. Comparable actions of nonneurotrophin growth factors were not affected. Surprisingly, at 0.1-100 nM, K-252b selectively enhanced the trophic action of neurotrophin-3 on central cholinergic neurons, peripheral sensory neurons, and PC12 cells. In PC12 cells, K-252b potentiated the neurotrophin-3-induced tyrosine phosphorylation of trk, a protein kinase responsible for transmitting neurotrophin signals. Of the three structurally related nerve growth factor inhibitors, K-252a, K-252b, and staurosporine, only the first two also mediated neurotrophin-3 potentiation. These findings indicate that K-252b generally and selectively potentiates the neurotrophic action of neurotrophin-3 and suggest that this action involves trk-type neurotrophin receptors. C1 UNIV SO CALIF,DEPT BIOL SCI,LOS ANGELES,CA 90089. NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,FREDERICK,MD 21701. GENENTECH INC,S SAN FRANCISCO,CA. RP KNUSEL, B (reprint author), UNIV SO CALIF,ETHEL PERCY ANDRUS GERONTOL CTR,UNIV PK,MC-0191,LOS ANGELES,CA 90089, USA. FU NCI NIH HHS [N01-CO-74101]; NIA NIH HHS [AG09793]; NINDS NIH HHS [NS22933] NR 49 TC 58 Z9 58 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 1992 VL 59 IS 2 BP 715 EP 722 DI 10.1111/j.1471-4159.1992.tb09427.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA JD599 UT WOS:A1992JD59900044 PM 1629741 ER PT J AU DRESCHER, DG UPADHYAY, S WILCOX, E FEX, J AF DRESCHER, DG UPADHYAY, S WILCOX, E FEX, J TI ANALYSIS OF MUSCARINIC RECEPTOR SUBTYPES IN THE MOUSE COCHLEA BY MEANS OF THE POLYMERASE CHAIN-REACTION SO JOURNAL OF NEUROCHEMISTRY LA English DT Note DE MUSCARINIC RECEPTORS; ACETYLCHOLINE; POLYMERASE CHAIN REACTION; COCHLEA ID OUTER HAIR-CELLS; GUINEA-PIG COCHLEA; ACETYLCHOLINE-RECEPTOR; RAT COCHLEA; EXPRESSION; BINDING; GENES; CLONING; NUCLEUS AB Total RNA was extracted with guanidine thiocyanate from the cochleas of 16-day-old CBA(J) mice. The mRNA was purified from the total RNA using oligo-dT cellulose, and the mRNA was treated with DNase to degrade genomic DNA. After reverse transcription, resulting cDNA was amplified by polymerase chain reaction (PCR), using primers specific for the nucleotide sequences m1-m5, representing subtypes of muscarinic acetylcholine receptors. PCR products corresponding to subtypes m1, m3, and m5, but not to m2 and m4, were amplified. These results suggest that muscarinic acetylcholine receptors of these odd-numbered subtypes are expressed in the mammalian cochlea. C1 NIDOCD,MOLEC BIOL LAB,BETHESDA,MD. WAYNE STATE UNIV,SCH MED,DEPT BIOCHEM,DETROIT,MI 48201. RP DRESCHER, DG (reprint author), WAYNE STATE UNIV,SCH MED,DEPT OTOLARYNGOL,BIOOTOL LAB,540 E CANFIELD AVE,DETROIT,MI 48201, USA. FU NIDCD NIH HHS [R01 DC 00156] NR 31 TC 44 Z9 46 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 1992 VL 59 IS 2 BP 765 EP 767 DI 10.1111/j.1471-4159.1992.tb09436.x PG 3 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA JD599 UT WOS:A1992JD59900053 PM 1629746 ER PT J AU CAUGHEY, B RACE, RE AF CAUGHEY, B RACE, RE TI POTENT INHIBITION OF SCRAPIE-ASSOCIATED PRP ACCUMULATION BY CONGO RED SO JOURNAL OF NEUROCHEMISTRY LA English DT Note DE CONGO RED; AMYLOID; PRP; SCRAPIE-PRION; THERAPY ID PRION PROTEIN-BIOSYNTHESIS; CREUTZFELDT-JAKOB DISEASE; IDENTIFICATION; MICE; INFECTIVITY; FIBRILS; LINKAGE; CELLS; BRAIN; GENE AB Transmissible spongiform encephalopathies (prion diseases), Alzheimer's disease, and other amyloidoses result in the accumulation of certain abnormally stable Proteins that are thought by many to play central roles in disease pathogenesis. Using scrapie-infected neuroblastoma cells as a model system, we found that Congo red, an amyloid-binding dye, potently inhibits the accumulation of the scrapie-associated, protease-resistant isoform of protein PrP without affecting the metabolism of the normal isoform. Growth of the cells with submicromolar concentrations of Congo red for 5 days reduced the amount of protease-resistant PrP detected in the cultures by >90%. This activity of Congo red suggests that it selectively disrupts the conversion of PrP to the protease-resistant isoform or destabilizes this isoform once it is made. Potential therapeutic applications of Congo red are discussed. RP CAUGHEY, B (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,903 S 4TH ST,HAMILTON,MT 59840, USA. NR 27 TC 196 Z9 206 U1 2 U2 7 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 1992 VL 59 IS 2 BP 768 EP 771 DI 10.1111/j.1471-4159.1992.tb09437.x PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA JD599 UT WOS:A1992JD59900054 PM 1352803 ER PT J AU FISCHERCOLBRIE, R ESKAY, RL EIDEN, LE MAAS, D AF FISCHERCOLBRIE, R ESKAY, RL EIDEN, LE MAAS, D TI TRANSSYNAPTIC REGULATION OF GALANIN, NEUROTENSIN, AND SUBSTANCE-P IN THE ADRENAL-MEDULLA - COMBINATORIAL CONTROL BY 2ND-MESSENGER SIGNALING PATHWAYS SO JOURNAL OF NEUROCHEMISTRY LA English DT Note DE ADRENAL MEDULLA; NEUROTENSIN; SUBSTANCE-P; GALANIN; 2ND-MESSENGERS; PROTEIN KINASE-A PATHWAY; PROTEIN KINASE-C PATHWAY; CALCIUM PATHWAY; HYPOGLYCEMIC SHOCK ID BOVINE CHROMAFFIN CELLS; PROENKEPHALIN GENE-EXPRESSION; MESSENGER-RNA LEVELS; PROTEIN KINASE-C; NEUROPEPTIDE-Y; CHROMOGRANIN-A; ENKEPHALIN; BIOSYNTHESIS; PEPTIDES; CALCIUM AB The adrenomedullary content of neurotensin and substance P was examined 1, 6, and 12 days after hypoglycemic shock. The neurotensin content was increased 60-fold within 24 h and remained elevated for up to 12 days, whereas the substance P content was increased approximately sevenfold within 24 h of insulin treatment and returned to control levels by 12 days poststimulation. Because protein kinase A, protein kinase C, and calcium influx in the rat adrenal medulla are all stimulated following splanchnic nerve stimulation, the differential regulation of neurotensin and substance P biosynthesis following stimulation of these three pathways was examined in bovine chromaffin cells in vitro. Neurotensin levels were up-regulated by elevated potassium, forskolin, and phorbol ester in bovine chromaffin cells. Substance P levels were up-regulated by elevated potassium and forskolin but not by phorbol ester treatment. When chromaffin cells were treated with phorbol ester in combination with forskolin, neurotensin levels were increased in a synergistic fashion, whereas phorbol ester antagonized the forskolin-induced elevation of substance P levels. Earlier, it was reported that galanin biosynthesis, like neurotensin biosynthesis, is upregulated by depolarization, phorbol ester stimulation, and forskolin treatment in chromaffin cells in vitro. Here we report that galanin is also, like neurotensin, increased >60-fold after stimulation of the rat adrenal medulla in vivo. Neuropeptide-specific combinatorial effects of stimulating the calcium, protein kinase A, and protein kinase C signaling pathways may underlie the quantitative differences between galanin and neurotensin compared with substance P up-regulation in rat adrenal medulla after splanchnic nerve stimulation in vivo. C1 NIMH,CELL BIOL LAB,MOLEC & CELLULAR NEUROBIOL UNIT,BLDG 36,ROOM 3A-17,BETHESDA,MD 20892. UNIV INNSBRUCK,DEPT PHARMACOL,A-6020 INNSBRUCK,AUSTRIA. NIAAA,CLIN STUDIES LAB,BETHESDA,MD. NR 22 TC 43 Z9 43 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 1992 VL 59 IS 2 BP 780 EP 783 DI 10.1111/j.1471-4159.1992.tb09440.x PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA JD599 UT WOS:A1992JD59900057 PM 1378491 ER PT J AU CHIAVAROLI, C COOPER, DMF BOYAJIAN, CL MURRAYWHELAN, R DEMAUREX, N SPIEGEL, AM SCHLEGEL, W AF CHIAVAROLI, C COOPER, DMF BOYAJIAN, CL MURRAYWHELAN, R DEMAUREX, N SPIEGEL, AM SCHLEGEL, W TI SPONTANEOUS INTRACELLULAR CALCIUM OSCILLATIONS AND GS-ALPHA SUBUNIT EXPRESSION ARE INVERSELY CORRELATED WITH SECRETORY GRANULE CONTENT IN PITUITARY-CELLS SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE GH4C1 CELLS; G-PROTEINS; [CA-2+]I OSCILLATIONS; SECRETORY GRANULES ID NUCLEOTIDE-BINDING-PROTEIN; THYROTROPIN-RELEASING-HORMONE; GH3 CELLS; ACTION-POTENTIALS; PROLACTIN SECRETION; CYTOSOLIC CALCIUM; ADENYLYL CYCLASE; GROWTH-HORMONE; CLONAL STRAIN; GH4C1 CELLS AB Cells of the pituitary tumour cell line GH4C1 were exposed to epidermal growth factor, estradiol and insulin for 5 days, a treatment which resulted in 1) increased prolactin storage in secretory granules, 2) the loss of spontaneous [Ca2+]i oscillations, and 3) a selective reduction of the protein G(s)alpha, seen in immunoblots, cholera toxin labelling, and vasoactive intestinal peptide stimulation of adenylyl cyclase. In contrast, the glucocorticoid dexamethasone, which increases the expression of G(s)alpha, partially restored spontaneous [Ca2+]i oscillations and decreased prolactin storage. It is concluded that G(s)alpha-levels in tumoral cells result in spontaneous electrical activity which may empty prolactin stores by the continuous activation of exocytosis. C1 UNIV GENEVA,DEPT MED,FDN RECH MED,64 AVE ROSERAIE,CH-1211 GENEVA,SWITZERLAND. NIDDKD,PATHOPHYSIOL BRANCH,BETHESDA,MD 20892. UNIV COLORADO,HLTH SCI CTR,DEPT PHARMACOL,DENVER,CO 80262. NR 55 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD AUG PY 1992 VL 4 IS 4 BP 473 EP 481 DI 10.1111/j.1365-2826.1992.tb00195.x PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA JG677 UT WOS:A1992JG67700013 PM 21554632 ER PT J AU PONS, TP GARRAGHTY, PE MISHKIN, M AF PONS, TP GARRAGHTY, PE MISHKIN, M TI SERIAL AND PARALLEL PROCESSING OF TACTUAL INFORMATION IN SOMATOSENSORY CORTEX OF RHESUS-MONKEYS SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID MACAQUE MONKEYS; LATERAL SULCUS; CORTICAL AREA; SOMATOTOPIC ORGANIZATION; SAIMIRI-SCIUREUS; PARIETAL CORTEX; SQUIRREL-MONKEY; BODY-SURFACE; 2ND; CONNECTIONS AB 1. Selective ablations of the hand representations in postcentral cortical areas 3a, 3b, 1, and 2 were made in different combinations to determine each area's contribution to the responsivity and modality properties of neurons in the hand representation in SII. 2. Ablations that left intact only the postcentral areas that process predominantly cutaneous inputs (i.e., areas 3b and 1) yielded SII recording sites responsive to cutaneous stimulation and none driven exclusively by high-intensity or "deep" stimulation. Conversely, ablations that left intact only the postcentral areas that process predominantly deep receptor inputs (i.e., areas 3a and 2) yielded mostly SII recording sites that responded exclusively to deep stimulation. 3. Ablations that left intact only area 3a or only area 2 yielded substantial and roughly equal reductions in the number of deep receptive fields in SII. By contrast, ablations that left intact only area 3b or only area 1 yielded unequal reductions in the number of cutaneous receptive fields in SII: a small reduction when area 3b alone was intact but a somewhat larger one when only area 1 was intact. 4. Finally, when the hand representation in area 3b was ablated, leaving areas 3a, 1, and 2 fully intact, there was again a substantial reduction in the encounter rate of cutaneous receptive fields. 5. The partial ablations often led to unresponsive sites in the SII hand representation. In SII representations other than of the hand no such unresponsive sites were found and there were no substantial changes in the ratio of cutaneous to deep receptive fields, indicating that the foregoing results were not due to long-lasting postsurgical depression or effects of anesthesia. 6. The findings indicate that modality-specific information is relayed from postcentral cortical areas to SII along parallel channels, with cutaneous inputs transmitted via areas 3b and 1, and deep inputs via areas 3a and 2. Further, area 3b provides the major source of cutaneous input to SII, directly and perhaps also via area 1. 7. The results are in line with accumulating anatomic and electrophysiological evidence pointing to an evolutionary shift in the organization of the somatosensory system from the general mammalian plan, in which tactile information is processed in parallel in SI and SII, to a new organization in higher primates in which the processing of tactile information proceeds serially from SI to SII. The presumed functional advantages of this evolutionary shift are unknown. RP PONS, TP (reprint author), NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892, USA. NR 46 TC 122 Z9 123 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD AUG PY 1992 VL 68 IS 2 BP 518 EP 527 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA JJ412 UT WOS:A1992JJ41200016 PM 1527572 ER PT J AU POULTER, MO BARKER, JL OCARROLL, AM LOLAIT, SJ MAHAN, LC AF POULTER, MO BARKER, JL OCARROLL, AM LOLAIT, SJ MAHAN, LC TI DIFFERENTIAL AND TRANSIENT EXPRESSION OF GABA-A RECEPTOR ALPHA-SUBUNIT MESSENGER-RNAS IN THE DEVELOPING RAT CNS SO JOURNAL OF NEUROSCIENCE LA English DT Article ID CEREBELLAR GRANULE CELLS; A RECEPTOR; BENZODIAZEPINE RECEPTORS; FUNCTIONAL EXPRESSION; MOLECULAR-BIOLOGY; GABAERGIC SYSTEM; XENOPUS OOCYTES; SPINAL-CORD; BRAIN; PHARMACOLOGY AB The expression of mRNAs coding for alpha-1, alpha-2, alpha-3, alpha-5, and alpha-6 subunits of the GABA(A) neurotransmitter receptor was followed during the development of the rat CNS by in situ hybridization histochemistry. Expression of these subunit mRNAs in tissue sections of embryonic day 15 and 17 (E15, E17) whole rat and in brain at ages >E17 to adult were varied, transient, and region specific. Subunit mRNAs first detected at E15 were those coding for the alpha-2 and alpha-3 subunits. At E17, alpha-2, alpha-3, and alpha-5, mRNAs were present in abundance in numerous are as in the CNS, with lower but significant amounts of alpha-6 being present in the cortical neuroepithelial layers. However, alpha-6 subunit mRNA expression in the cortex declined until little or no alpha-6 mRNA was detected at E19. Alpha-1 subunit mRNA first appeared at E19 in the cortex, followed by expression in the hippocampus by postnatal 5 (PN5). Particularly high expression of alpha-2 and alpha-5 subunit mRNAs was detected throughout the developing CNS, but they were most abundant in the olfactory bulb neurons. The high levels of alpha-2 and alpha-5 subunit mRNAs began to decline around PN5 to the amounts observed in adult. These results demonstrate that numerous GABA(A) receptor alpha-subunits are expressed before birth in a region- and age-specific manner. This complex and varied expression supports the hypothesis that GABA may play a role in cellular and synaptic differentiation. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RP POULTER, MO (reprint author), NINCDS,NEUROPHYSIOL LAB,BLDG 36,ROOM 2C02,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Poulter, Michael/K-3909-2013 OI Poulter, Michael/0000-0001-7469-8462 NR 50 TC 213 Z9 215 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG PY 1992 VL 12 IS 8 BP 2888 EP 2900 PG 13 WC Neurosciences SC Neurosciences & Neurology GA JH370 UT WOS:A1992JH37000002 PM 1322978 ER PT J AU CHARNAS, LR SZARO, BG GAINER, H AF CHARNAS, LR SZARO, BG GAINER, H TI IDENTIFICATION AND DEVELOPMENTAL EXPRESSION OF A NOVEL LOW-MOLECULAR-WEIGHT NEURONAL INTERMEDIATE FILAMENT PROTEIN EXPRESSED IN XENOPUS-LAEVIS SO JOURNAL OF NEUROSCIENCE LA English DT Article ID NERVOUS-SYSTEM; NEUROFILAMENT PROTEINS; ALPHA-INTERNEXIN; GENE-EXPRESSION; RAT-BRAIN; VIMENTIN; PERIPHERIN; ANTIBODIES; NOTOCHORD; EVOLUTION AB Xenopus laevis is a valuable model system for the study of vertebrate neuroembryogenesis. However, very few well-characterized nervous system-specific molecular markers are available for studies in this organism. We screened a X. laevis adult brain cDNA library using a cDNA probe for mouse low molecular weight neurofilament protein (NF-L) in order to identify neuron-specific intermediate filament proteins. Clones for two distinct neuron-specific intermediate filament proteins were isolated and sequenced. One of these encoded for a Xenopus NF-L (XNF-L) and the other for a novel neuron-specific Xenopus intermediate filament protein (XNIF) that was present earlier and more abundantly than XNF-L during development. XNIF contained a central rod domain with multiple sequence features characteristic of IF proteins. The XNF-L was very similar to mouse NF-L, with a 77% sequence identity in the rod domain and the presence of a polyglutamic acid region in the tail domain, characteristic of type IV neurofilament proteins. In contrast, XNIF showed only 60% identity to mouse NF-L in the rod domain and lacked the glutamic acid-rich sequence in the tail domain. XNIF also had a very low (approximately 38%) sequence identity in the head and tail domains as compared to NF-L and other neurofilament proteins (45% identity to the head domain of alpha-internexin). In the adult frog, XNIF mRNA is detected by Northern blots only within the nervous system and by in situ hybridization histochemistry exclusively in neurons, particularly in the medullary reticular system and spinal cord. Antisera raised against the unique tail region of XNIF detected a single distinct 60 kDa band in Western blots of nervous system cytoskeletal preparations, and this XNIF immunoreactivity was concentrated in axons in the PNS and in small perikarya in the dorsal root ganglion. in contrast, NF-L immunoreactivity was principally in the large perikarya in the dorsal root ganglion. In development, XNIF mRNA appears more abundant than XNF-L mRNA in all premetamorphic stages examined. XNIF mRNA is first detectable at stage 24 (26 hr), whereas stable expression of XNF-L is at stage 35/36 (50 hr). XNIF immunoreactivity is detectable within the cement gland, within many neuronal cell bodies and axon tracts within the developing nervous system, and within all cellular layers of the developing retina. The availability of these two distinct neuron-specific intermediate filament proteins, with different temporal and spatial expression patterns, should provide new markers as well as targets for functional perturbation in the developing X. laevis nervous system. C1 NICHHD,HUMAN GENET BRANCH,NEUROGENET UNIT,BETHESDA,MD 20892. NINCDS,NEUROCHEM LAB,BETHESDA,MD 20892. NR 55 TC 48 Z9 50 U1 1 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG PY 1992 VL 12 IS 8 BP 3010 EP 3024 PG 15 WC Neurosciences SC Neurosciences & Neurology GA JH370 UT WOS:A1992JH37000011 PM 1494944 ER PT J AU LELONG, IH PETEGNIEF, V REBEL, G AF LELONG, IH PETEGNIEF, V REBEL, G TI NEURONAL CELLS MATURE FASTER ON POLYETHYLENEIMINE COATED PLATES THAN ON POLYLYSINE COATED PLATES SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE NEURONS; CULTURES; MATURATION ID EMBRYO CEREBRAL HEMISPHERES; FIBROBLAST GROWTH-FACTOR; GLIAL-CELLS; EXTRACELLULAR-MATRIX; CULTURED NEURONS; DEVELOPMENTAL-CHANGES; GANGLIOSIDE PATTERNS; TISSUE-CULTURE; TAURINE UPTAKE; FETAL-RAT AB Cell morphology, protein/DNA ratio, ganglioside analysis, taurine uptake, and the activity of neurone specific enolase showed that neuronal cells mature faster when grown on polyethyleneimine coated plates compared to cells grown on polylysine coated plates. Our results also show higher protein/DNA ratio and total and neuron specific enolase activities in cells grown in serum supplemented medium, when compared to their counterparts grown in synthetic medium. Moreover, our results show that only some specific markers can be used to determine the early and late events of cell maturation, whereas other markers continuously vary with time. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. RP LELONG, IH (reprint author), CTR NEUROCHIM,5 RUE BLAISE PASCAL,F-67084 STRASBOURG,FRANCE. OI Petegnief, Valerie/0000-0002-2782-1891 NR 47 TC 34 Z9 34 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD AUG PY 1992 VL 32 IS 4 BP 562 EP 568 DI 10.1002/jnr.490320411 PG 7 WC Neurosciences SC Neurosciences & Neurology GA JE851 UT WOS:A1992JE85100010 PM 1527802 ER PT J AU BERLIN, E BHATHENA, SJ JUDD, JT NAIR, PP PETERS, RC BHAGAVAN, HN BALLARDBARBASH, R TAYLOR, PR AF BERLIN, E BHATHENA, SJ JUDD, JT NAIR, PP PETERS, RC BHAGAVAN, HN BALLARDBARBASH, R TAYLOR, PR TI EFFECTS OF OMEGA-3-FATTY-ACID AND VITAMIN-E SUPPLEMENTATION ON ERYTHROCYTE-MEMBRANE FLUIDITY, TOCOPHEROLS, INSULIN BINDING, AND LIPID-COMPOSITION IN ADULT MEN SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE ALPHA-TOCOPHEROL; INSULIN RECEPTOR; N-3 FATTY ACID; N-6 FATTY ACID; FISH OIL; MEMBRANE FLUIDITY ID FISH OIL SUPPLEMENTATION; CHOLESTEROL-FED RABBITS; ALPHA-TOCOPHEROL; PLATELET-AGGREGATION; DIETARY LIPIDS; CARDIOVASCULAR-DISEASE; HEALTHY-VOLUNTEERS; LIVER; N-3; PLASMA AB Dietary supplementation with an omega-3 fatty acid preparation (fish oil) together with pharmacologic doses of vitamin E increased both insulin binding and membrane fluidity in erythrocytes from human adult males. Supplementation with fish oil alone induced significant increases in the alpha- and gamma-tocopherol contents of the red blood cell membranes. Forty healthy men were given controlled diets and supplements, which together provided 40% of energy from fat (polyunsaturated:monosaturated:saturated ratio of 0.8:1:1), 360 mg cholesterol/day, and a minimum of 22 mg alpha-tocopherol (alpha-T)/day for three successive experimental periods of 10, 10, and 8 weeks, during which they were given capsules containing 15 g of a placebo oil/day, 15 g fish oil concentrate (FOC)/day, and 15 g fish oil + 200 IU alpha-T (FOC + alpha-T)/day, respectively. Erythrocyte ghost insulin binding (IB) and 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence-determined fluidity were significantly increased following the FOC + alpha-T period, however FOC alone had no effect. At the end of each experimental period, IB values, as percentage bound/100-mu-g ghost protein at 4-degrees-C, were 0.96, 0.91, and 1.35, and DPH steady state fluorescence anisotropies were 0.311, 0.303, and 0.296, at 4-degrees-C, respectively. Small but statistically significant decreases in fluorescence lifetimes further indicated increased fluidity. FOC supplementation resulted in significantly lower membrane cholesterol:phospholipid ratios and increased membrane tocopherols despite daily vitamin E consumption of only 22 mg as in the placebo period. Membrane incorporation of n-3 fatty acids was, however, limited. Thus, dietary polyunsaturated fatty acids exerted substantial effects on erythrocyte membranes by affecting membrane contents of lipid molecules other than the fatty acids. C1 HOFFMANN LA ROCHE INC,DEPT CLIN NUTR,NUTLEY,NJ 07110. NCI,DIV CANC PREVENT & CONTROL,CANC PREVENT STUDIES BRANCH,BETHESDA,MD 20892. RP BERLIN, E (reprint author), USDA ARS,BELTSVILLE AGR RES CTR,BELTSVILLE HUMAN NUTR RES CTR,LIPID & CARBOHYDRATE NUTR LABS,BELTSVILLE,MD 20705, USA. NR 71 TC 35 Z9 36 U1 0 U2 2 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD AUG PY 1992 VL 3 IS 8 BP 392 EP 400 DI 10.1016/0955-2863(92)90013-9 PG 9 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA JH764 UT WOS:A1992JH76400003 ER PT J AU ROSCOE, RJ STEENLAND, K MCCAMMON, CS SCHOBER, SE ROBINSON, CF HALPERIN, WE FINGERHUT, MA AF ROSCOE, RJ STEENLAND, K MCCAMMON, CS SCHOBER, SE ROBINSON, CF HALPERIN, WE FINGERHUT, MA TI COLON AND STOMACH-CANCER MORTALITY AMONG AUTOMOTIVE WOOD MODEL MAKERS SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID TABLE ANALYSIS SYSTEM; COLORECTAL-CANCER; RISK; PATTERN; WOODWORKERS; STATISTICS; WORKERS; POLYPS; COHORT AB Automotive wood model makers have been reported to be at excess risk for colon and other cancers in recent epidemiologic studies. To further explore these risks, we conducted a retrospective cohort mortality study, with follow-up from 1940 through 1984, of 2294 white male wood model makers employed at any time until 1980 by three US auto makers. Using US mortality rates for comparison, we found elevated standardized mortality ratios of 1.2 (95% CI, 0.8-1.9) for colon cancer and 1.6 (95% CI, 0.9-2.6) for stomach cancer. We also conducted nested case-control studies for 20 colon and 17 stomach cancer cases and 543 age-matched controls. We found no trend of increased risk for colon or stomach cancer mortality with increased exposure to wood dust or to duration employed in wood model making. C1 CTR DIS CONTROL,NIOSH,DENVER,CO. NIDA,ROCKVILLE,MD. RP ROSCOE, RJ (reprint author), CTR DIS CONTROL,NIOSH,R-15,4676 COLUMBIA PKWY,CINCINNATI,OH 45226, USA. NR 38 TC 20 Z9 21 U1 2 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD AUG PY 1992 VL 34 IS 8 BP 759 EP 768 DI 10.1097/00043764-199208000-00007 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA JJ219 UT WOS:A1992JJ21900003 ER PT J AU LAKSHMAN, MK SAYER, JM YAGI, H JERINA, DM AF LAKSHMAN, MK SAYER, JM YAGI, H JERINA, DM TI SYNTHESIS AND DUPLEX-FORMING PROPERTIES OF A NONANUCLEOTIDE CONTAINING AN N-6-DEOXYADENOSINE ADDUCT OF A BAY-REGION DIOL EPOXIDE SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; COVALENT NUCLEOSIDE ADDUCTS; DNA; ADENOSINE; BENZOPYRENE; 1,2-EPOXIDES; CARCINOGEN; ADENINE; GUANINE AB A protected derivative, corresponding to the adduct derived from trans opening of (+/-)-1-alpha,2-beta-dihydroxy-3-beta,4-beta-epoxy-1,2,3,4-tetrahydrophenanth rene (in which the benzylic hydroxyl and epoxide groups are trans, Phenanthrene diol epoxide-2) by the exocyclic amino group of 2-deoxyadenosine (dA), has been synthesized by couPling (+/-)-1-alpha,2-beta,3-beta-trihydroxy-4-alpha-amino-1,2,3,4-tetrahydrophenan threne with a disilyl derivative of 6-fluoro dA. The resulting pair of diastereomeric adducts was easily separated by HPLC, and the absolute configuration of each diastereomer was assigned from its CD spectrum by analogy to known tetrahydrophenanthrene analogs. The structures of these adducts were confirmed by comparison of the NMR spectra of the derived pentaacetates with those obtained for the corresponding compounds prepared from dAMP and phenanthrene diol epoxide-2. Acetylation of the free hydroxyl groups, desilylation of the sugar, 5'-O-(4,4'-dimethoxytrityl) protection, and generation of a 3'-O-[(NN-diisopropylamino)(beta-cyanoethoxy)phosphine] provided an intermediate that was incorporated, using modified solid-phase DNA synthesizer methodology, into the oligonucleotide d(GGT CA*C GAG) comprising codons 60-62 of the human K-ras b proto-oncogene sequence. The effect of an adduct on the T(m) values for duplexes formed by this nonamer with complementary strands in which the residue opposite the modified dA is T or either of the "mismatched" purine nucleosides dA or dG was determined. Replacement of T with dG opposite the modified dA has little or no effect on T(m), whereas replacement of T with dA decreases the T(m) of the modified duplex by 9-degrees-C. C1 NIDDK,BIOORGAN CHEM LAB,OXIDAT MECH SECT,BETHESDA,MD 20892. NR 24 TC 54 Z9 54 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD AUG PY 1992 VL 57 IS 17 BP 4585 EP 4590 DI 10.1021/jo00043a012 PG 6 WC Chemistry, Organic SC Chemistry GA JJ668 UT WOS:A1992JJ66800012 ER PT J AU GRANOFF, DM ANDERSON, EL OSTERHOLM, MT HOLMES, SJ MCHUGH, JE BELSHE, RB MEDLEY, F MURPHY, TV AF GRANOFF, DM ANDERSON, EL OSTERHOLM, MT HOLMES, SJ MCHUGH, JE BELSHE, RB MEDLEY, F MURPHY, TV TI DIFFERENCES IN THE IMMUNOGENICITY OF 3 HAEMOPHILUS-INFLUENZAE TYPE-B CONJUGATE VACCINES IN INFANTS SO JOURNAL OF PEDIATRICS LA English DT Article ID OUTER-MEMBRANE PROTEIN; HEMOPHILUS-INFLUENZAE; CAPSULAR POLYSACCHARIDE; ANTIBODY-RESPONSES; 6-MONTH-OLD INFANTS; RHESUS-MONKEYS; CHILDREN; DISEASE; IMMUNIZATION; POPULATION AB Objective: To compare the immunogenicity of three Haemophilus influenzae type b (Hib) conjugate vaccines in infants residing in different geographic areas. Design: A multicenter, randomized immunogenicity trial with sera assayed in one laboratory without knowledge of vaccine brand status. In Minneapolis and Dallas, infants were vaccinated at 2, 4, and 6 months of age; in St. Louis, infants were vaccinated at 2 and 4 months of age. Subjects: A convenience sample of 458 infants recruited largely from private pediatric practices. Measurements and results: At each of the study sites, the respective trends between the anticapsular antibody responses of the infants assigned to the different conjugate vaccine groups were similar. After one or two doses, Hib polysaccharide conjugated to outer membrane protein complex of Neisseria meningitidis (PRP-OMP) was more immunogenic than Hib polysaccharide-tetanus toxoid conjugate (PRP-T), or Hib oligomers conjugated to the mutant diphtheria toxin CRM197 (HbOC) (p<0.001). After two doses, PRP-T was more immunogenic than HbOC (p less-than-or-equal-to 0.001). After three doses there was no significant difference in the geometric mean antibody concentrations of the three groups, and 88% to 97% of the infants had >1.0-mu-g/ml of antibody. The HbOC vaccine elicited a 10-fold lower antibody response after two doses (0.45-mu-g/ml vs 5.9-mu-g/ml) and a threefold lower antibody response after three doses (6.3-mu-g/ml vs 22.9-mu-g/ml) than observed by us previously with a prelicensure lot of this vaccine (p <0.001). Because of these low responses, the infants in St. Louis who received two doses of HbOC were revaccinated with unconjugated PRP at a mean age of 8.9 months. This group was immunologically primed, as evidenced by a 10-fold increase in geometric mean antibody concentration after vaccination at an age when unprimed infants do not normally respond to this vaccine. Conclusions: In infants in three geographic regions, PRP-OMP elicited earlier acquisition of serum antibody than the other two conjugate vaccines; however, after three doses the antibody concentrations of the three groups were not significantly different. The reason for the markedly lower immunogenicity of HbOC vaccine than reported previously is unknown. C1 WASHINGTON UNIV, SCH MED, EDWARD MALLINCKRODT DEPT PEDIAT, ST LOUIS, MO 63110 USA. ST LOUIS UNIV, SCH MED, NIAID, VACCINE EVALUAT UNIT, ST LOUIS, MO 63104 USA. ST LOUIS UNIV, SCH MED, DEPT PEDIAT, ST LOUIS, MO 63104 USA. ST LOUIS UNIV, SCH MED, DEPT MED, ST LOUIS, MO 63104 USA. WAYZATA CHILDRENS CLIN, MINNEAPOLIS, MN USA. MINNESOTA DEPT HLTH, MINNEAPOLIS, MN USA. UNIV TEXAS, SW MED CTR, DEPT PEDIAT, DALLAS, TX 75230 USA. FU NIAID NIH HHS [AI 17962, AI 05064, AI 21842] NR 28 TC 108 Z9 110 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD AUG PY 1992 VL 121 IS 2 BP 187 EP 194 DI 10.1016/S0022-3476(05)81186-2 PG 8 WC Pediatrics SC Pediatrics GA JH129 UT WOS:A1992JH12900003 PM 1640282 ER PT J AU MUNICCHI, G MALOZOWSKI, S NISULA, BC CRISTIANO, A ROSE, SR AF MUNICCHI, G MALOZOWSKI, S NISULA, BC CRISTIANO, A ROSE, SR TI NOCTURNAL THYROTROPIN SURGE IN GROWTH HORMONE-DEFICIENT CHILDREN SO JOURNAL OF PEDIATRICS LA English DT Article ID REVERSE T3; THYROXINE; HYPOTHYROIDISM; TSH; T4; TRIIODOTHYRONINE; SOMATOSTATIN; CONVERSION; CHILDHOOD; SECRETION AB Because some patients with growth hormone (GH) deficiency are found to be hypothyroid after initiation of treatment with GH, we assessed the predictive value of the nocturnal thyrotropin surge (a sensitive test for central hypothyroidism) in 56 untreated GH-deficient children and adolescents. Eighteen patients had a subnormal thyrotropin surge (mean 18% (range -30% to +46%)), significantly less than that of 96 normal control subjects (mean 124%; 95% confidence limits, 47% to 300%; p <0.01); 13 of the 18 had a subnormal total thyroxine (T4) level or a subnormal free T4 level, or both. These 18 patients were given thyroid hormone replacement therapy; GH deficiency was confirmed during treatment with thyroxine. Of the remaining 38 patients, who had no initial evidence of dysfunction of the hypothalamic-pituitary-thyroid axis, 23 were reexamined while they were receiving GH treatment. Hypothyroidism developed in none of those 23 children during GH therapy. The nocturnal thyrotropin surge test and determination of iodothyronine levels were repeated in 14 of these euthyroid patients. There was no significant change in mean thyrotropin surge (129% (range +49% to +300%) vs 125% (range +51% to +222%)), mean serum level of total T4 (111 +/- 4 vs 103 +/- 3 nmol/L), mean serum level of free T4 (19 +/- 0.7 vs 18 +/- 0.8 pmol/L), mean serum level of triiodothyronine (2.5 +/- 0.1 vs 2.5 +/- 0.1 nmol/L), or mean serum level of thyrotropin (2.9 +/- 0.3 vs 2.9 + 0.5 mU/L (mean +/- SEM)). We conclude that GH treatment does not appreciably alter thyroid function in GH-deficient patients who have no evidence of thyroid axis dysfunction before GH treatment. C1 UNIV NEW MEXICO, MED CTR, DEPT PEDIAT, ALBUQUERQUE, NM 87131 USA. RP MUNICCHI, G (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N262, BETHESDA, MD 20892 USA. NR 26 TC 24 Z9 26 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD AUG PY 1992 VL 121 IS 2 BP 214 EP 220 DI 10.1016/S0022-3476(05)81191-6 PG 7 WC Pediatrics SC Pediatrics GA JH129 UT WOS:A1992JH12900008 PM 1640286 ER PT J AU REVENIS, ME KALINER, MA AF REVENIS, ME KALINER, MA TI LACTOFERRIN AND LYSOZYME DEFICIENCY IN AIRWAY SECRETIONS - ASSOCIATION WITH THE DEVELOPMENT OF BRONCHOPULMONARY DYSPLASIA SO JOURNAL OF PEDIATRICS LA English DT Article ID INDUCED NASAL SECRETIONS; LINKED IMMUNOSORBENT-ASSAY; PATHO-PHYSIOLOGY; GLANDULAR SECRETION; RHINITIS; NEUTROPHILS; PROTEIN; PLASMA; IMMUNOASSAY; ANTIOXIDANT AB To test whether the Presence of airway inflammatory markers differentiated babies with hyaline membrane disease (HMD) who recovered (n = 18) from those in whom bronchopulmonary dysplasia (BPD) developed (n = 18), tracheal aspirate samples from 36 newborn infants with HMD who underwent intubation were collected during days 1 to 28 of life and analyzed for the mucosal antimicrobial proteins lactoferrin and lysozyme. For babies with HMD in whom BPD developed, lactoferrin concentrations were decreased during the first 4 days of life (7 +/- 3, 14 +/- 3, 18 +/- 3, and 18 +/- 3-mu-g/ml, respectively) in comparison with those in babies with HMD who recovered (23 +/- 8, 29 +/- 6, 41 +/- 9, and 81 +/- 19-mu-g/ml); group differences reached statistical significance on days 3 and 4 (p <0.05). Lysozyme levels in the secretions of babies with BPD were also lower on day 3 (31 +/- 5-mu-g/ml) than in those of babies who recovered (54 +/- 7.5-mu-g/ml). For babies with BPD whose endotracheal tube remained in place beyond day 4, lysozyme levels on days 5 to 12 were significantly lower for those classified as having severe BPD than for those with mild to moderate BPD. Because lysozyme and lactoferrin are products of serous cells found in submucous glands, it seems possible that the relative immaturity of submucous glands may influence the development of BPD. C1 NIH, CLIN INVEST LAB, ALLERG DIS SECT, BETHESDA, MD 20892 USA. RP REVENIS, ME (reprint author), GEORGE WASHINGTON UNIV, CHILDRENS NATL MED CTR, SCH MED & HLTH SCI, DEPT NEONATOL, WASHINGTON, DC 20010 USA. NR 28 TC 23 Z9 24 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD AUG PY 1992 VL 121 IS 2 BP 262 EP 270 DI 10.1016/S0022-3476(05)81201-6 PG 9 WC Pediatrics SC Pediatrics GA JH129 UT WOS:A1992JH12900017 PM 1640295 ER PT J AU TELLA, SR SCHINDLER, CW GOLDBERG, SR AF TELLA, SR SCHINDLER, CW GOLDBERG, SR TI CARDIOVASCULAR EFFECTS OF COCAINE IN CONSCIOUS RATS - RELATIVE SIGNIFICANCE OF CENTRAL SYMPATHETIC-STIMULATION AND PERIPHERAL NEURONAL MONOAMINE UPTAKE AND RELEASE MECHANISMS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; CARDIAC RESPONSES; GENERAL-ANESTHETICS; SQUIRREL-MONKEYS; DOGS; NOREPINEPHRINE; HUMANS; PHARMACOKINETICS; DISPOSITION; HEART AB Cocaine (0.03-3 mg/kg, i.v.) produced a dose-dependent increase in mean arterial blood pressure and heart rate in conscious Sprague-Dawley rats. Pretreatment with the competitive ganglionic blockers pentolinium or hexamethonium attenuated cocaine's pressor effect, whereas noncompetitive (chlorisondamine) or mixed (mecamylamine) type blockers not only abolished, but also reversed it to a depressor effect. Cocaine's tachycardiac effect was attenuated by all four ganglionic blockers. The relative effectiveness of the four ganglionic blockers in antagonizing cocaine-induced cardiovascular effects was similar to that of antagonism of phenylephrine-induced, centrally mediated reflex bradycardia. All four ganglionic blockers at all the doses tested produced similar reductions in base-line BP, thereby suggesting that these agents produced similar degrees of maximal reduction of basal sympathetic tone. The pressor responses to norepinephrine (0.2-mu-g/kg) were potentiated, whereas those to tyramine (0.3 mg/kg) were inhibited by cocaine (0.3-3 mg/kg); the former effect was not dose dependent (bell-shaped dose-response curve), whereas the latter effect was dose-dependent. The amine uptake inhibitory potency (ED50, 0.85 mg/kg) of cocaine is about 10 times less than its potency to produce pressor (ED50, 0.075 mg/kg) and tachycardiac (ED50, 0.083 mg/kg) effects. Chlorisondamine did not antagonize the pressor effects of the indirect sympathomimetic agent, tyramine. These results suggest that the blockade of cocaine's pressor and tachycardiac effects by ganglionic blockers is not related to their ability to eliminate basal sympathetic tone and, thereby, indirectly blunt cocaine's inhibitory effect on sympathetic neuronal uptake of norepinephrine. Rather, the results indicate that these effects are mainly due to their antagonistic actions on cocaine-induced central stimulation of sympathetic activity. Thus, the cardiovascular effects of cocaine in conscious rats are mainly of central nervous system origin. Cocaine's peripheral actions, namely, release of norepinephrine from sympathetic nerve terminals and inhibition of sympathetic neuronal uptake of norepinephrine, are not critical for triggering its peak cardiovascular effects, C1 GEORGETOWN UNIV,SCH MED,DEPT PHARMACOL,WASHINGTON,DC. RP TELLA, SR (reprint author), NIDA,ADDICT RES CTR,PRECLIN PHARMACOL LAB,BEHAV PHARMACOL & GENET SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 73 TC 55 Z9 55 U1 3 U2 3 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 AUG PY 1992 VL 262 IS 2 BP 602 EP 610 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JH661 UT WOS:A1992JH66100022 PM 1501115 ER PT J AU MCCABE, RT NEWMAN, AH SKOLNICK, P AF MCCABE, RT NEWMAN, AH SKOLNICK, P TI AHN-683 - A FLUORESCENT LIGAND FOR PERIPHERAL-TYPE BENZODIAZEPINE RECEPTORS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DOPAMINE-RECEPTORS; PARTIAL-PURIFICATION; BINDING; VISUALIZATION; PHARMACOLOGY; SELECTIVITY; AFFINITY; SITE; D1 AB AHN 683 [1-(2-fluoro-5-N[1,3-dihydrol-1,1-bis(4-hydroxyphenyl)-3-oxo-5-isobenzofurancarboxamide]-phenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide] is a fluorescein-derived ligand at peripheral-type benzodiazepine receptors structurally related to the isoquinoline carboxamide, PK 14105. The binding of AHN 683 to rat renal membranes measured by fluorescence techniques was saturable with a maximum number of binding sites of 2.3 +/- 0.3 pmol/mg of protein. The K(D) (40.4 +/-2.2 nM) estimated by fluorescence was in good agreement with the K(i) (77.4 +/- 13.5 nM) obtained in competition studies with [H-3] Ro 5-4864. AHN 683 exhibited rapid and reversible binding which was significantly reduced by the histidine modifying reagent, diethylpyrocarbonate. The potencies of a pair of isoquinoline carboxamide enantiomers as well as other structurally diverse peripheral-type benzodiazepine receptor ligands estimated by inhibition of AHN 683 binding were in good agreement with values obtained using radioligand binding techniques. AHN 683 binding was unaffected by compounds that do not recognize peripheral-type benzodiazepine receptors. Moreover, a significant increase in the maximum number of binding sites of AHN 683 to rat renal membranes after chronic furosemide treatment (29.2%, P < .02) was comparable to the increase measured using [H-3]PK 11195 (35.6%, P < .001). These findings demonstrate the feasibility of using fluorescent ligand binding techniques to quantitatively characterize peripheral-type benzodiazepine receptors. C1 NIDDKD,NEUROSCI LAB,BETHESDA,MD. WALTER REED ARMY MED CTR,DEPT APPL BIOCHEM,WASHINGTON,DC 20307. NR 18 TC 5 Z9 5 U1 0 U2 1 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 AUG PY 1992 VL 262 IS 2 BP 734 EP 740 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JH661 UT WOS:A1992JH66100039 PM 1323661 ER PT J AU PITT, CG WANG, J CHIGNELL, CF SIK, R AF PITT, CG WANG, J CHIGNELL, CF SIK, R TI ESR SPECTROSCOPY AS A PROBE OF THE MORPHOLOGY OF HYDROGELS SO JOURNAL OF POLYMER SCIENCE PART B-POLYMER PHYSICS LA English DT Note DE ESR; HYDROGELS; MORPHOLOGY; WATER; PHEMA ID LIQUID-CHROMATOGRAPHY; COEFFICIENTS; PARTITION; WATER C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. RP PITT, CG (reprint author), AMGEN INC,THOUSAND OAKS,CA 91320, USA. NR 12 TC 8 Z9 8 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-6266 J9 J POLYM SCI POL PHYS JI J. Polym. Sci. Pt. B-Polym. Phys. PD AUG PY 1992 VL 30 IS 9 BP 1069 EP 1071 DI 10.1002/polb.1992.090300914 PG 3 WC Polymer Science SC Polymer Science GA JD982 UT WOS:A1992JD98200014 ER PT J AU WADE, TP KASID, A STEIN, CA LAROCCA, RV SARGENT, ER GOMELLA, LG MYERS, CE LINEHAN, WM AF WADE, TP KASID, A STEIN, CA LAROCCA, RV SARGENT, ER GOMELLA, LG MYERS, CE LINEHAN, WM TI SURAMIN INTERFERENCE WITH TRANSFORMING GROWTH-FACTOR-BETA INHIBITION OF HUMAN RENAL-CELL CARCINOMA IN CULTURE SO JOURNAL OF SURGICAL RESEARCH LA English DT Article ID FACTOR RECEPTOR; DIFFERENTIATION; BINDING; RNA C1 NCI,MED BRANCH,BETHESDA,MD 20892. RP WADE, TP (reprint author), NCI,SURG BRANCH,ROOM 2B42,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 17 TC 31 Z9 31 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 0022-4804 J9 J SURG RES JI J. Surg. Res. PD AUG PY 1992 VL 53 IS 2 BP 195 EP 198 PG 4 WC Surgery SC Surgery GA JN949 UT WOS:A1992JN94900014 PM 1405609 ER PT J AU KARPATI, S AF KARPATI, S TI INSITU LOCALIZATION OF IGG IN EPIDERMOLYSIS-BULLOSA ACQUISITA BY IMMUNOGOLD TECHNIQUE SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter RP KARPATI, S (reprint author), NCI,DERMATOL BRANCH,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD AUG PY 1992 VL 27 IS 2 BP 280 EP 280 DI 10.1016/S0190-9622(08)80753-0 PN 1 PG 1 WC Dermatology SC Dermatology GA JG537 UT WOS:A1992JG53700038 PM 1290534 ER PT J AU COTUGNA, N SUBAR, AF HEIMENDINGER, J KAHLE, L AF COTUGNA, N SUBAR, AF HEIMENDINGER, J KAHLE, L TI NUTRITION AND CANCER PREVENTION KNOWLEDGE, BELIEFS, ATTITUDES, AND PRACTICES - THE 1987 NATIONAL-HEALTH INTERVIEW SURVEY SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID GUIDELINES AB This article examines the nutrition and cancer prevention knowledge, beliefs, attitudes, and self-reported dietary changes of a US national probability sample. The data were drawn from the Cancer Control Supplement of the 1987 National Health Interview Survey, which was answered by 22,043 adults. Thirty-five percent of the sample reported that they had made dietary changes in the past 1 to 5 years for health reasons. Respondents reported eating more vegetables, fruit, lower-fat meats, and whole grains/fiber and less high-fat meats, fats, sweets/snacks, salty foods, refined grain products, alcohol, and dairy products. Those who did not make any dietary changes most, often said the reason,was that they enjoyed the food they were presently eating and did not want to make any changes. More than 90% of the sample agreed that diet and disease were related and 73% knew that diet and cancer were related, yet 44% believed there was nothing a person could do to reduce the risk of getting cancer or didn't know what could be done. In response to open-ended questions about foods that either increase or decrease cancer risk, vegetables, whole grains/fiber, fruit, and lower-fat meats were thought to decrease risk, and high-fat meats, fats, alcohol, sweets/snacks, and additives were thought to increase cancer risk. We found education and income levels to be the major demographic variables that have an impact on cancer prevention knowledge, attitudes, and beliefs. People with lower incomes and at lower educational levels should be targeted for education about cancer risk reduction. C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD 20904. RP COTUGNA, N (reprint author), UNIV DELAWARE,DEPT NUTR & DIETET,NEWARK,DE 19716, USA. NR 17 TC 90 Z9 91 U1 0 U2 3 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD AUG PY 1992 VL 92 IS 8 BP 963 EP 968 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA JG898 UT WOS:A1992JG89800012 PM 1640040 ER PT J AU BLOCK, G SUBAR, AF AF BLOCK, G SUBAR, AF TI ESTIMATES OF NUTRIENT INTAKE FROM A FOOD FREQUENCY QUESTIONNAIRE - THE 1987 NATIONAL-HEALTH INTERVIEW SURVEY SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID UNITED-STATES POPULATION; DIET; VALIDATION AB Nutrient intake data are reported from a 60-item food frequency questionnaire administered in the 1987 National Health Interview Survey to a representative sample of US adults 18 to 99 years of age (n=22,080). These data provide for the first time an estimate of the distribution of usual nutrient intakes in a national probability sample. For several nutrients, 10% to 25% of respondents may habitually consume substantially less than the Recommended Dietary Allowance, despite apparently adequate group means. Hispanics reported higher energy and carbohydrate intakes and a lower percentage of energy from fat than blacks or whites (35.6%, 38.4%, and 38.7% of energy from fat for Hispanics, blacks, and whites, respectively.) Whites had lower cholesterol intake than the other two groups, and blacks had a higher intake of sweets. Alcohol intake was lower among women and persons older than 65 years, but no other differences in alcohol intake emerged. Use of adjustment factors improved nutrient intake estimates from this shortened questionnaire to levels similar to those obtained from other national dietary surveys. The nutrient intake data from this research can be used to compare demographic subgroups and to describe the mean and distribution of nutrient intake. Furthermore, this research provides national reference data to investigators who use this or related questionnaires in nutrition research. C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. RP BLOCK, G (reprint author), UNIV CALIF BERKELEY,PUBL HLTH NUTR,BERKELEY,CA 94720, USA. RI Block, Gladys/E-3304-2010 NR 18 TC 186 Z9 186 U1 3 U2 6 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD AUG PY 1992 VL 92 IS 8 BP 969 EP 977 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA JG898 UT WOS:A1992JG89800013 PM 1640041 ER PT J AU BURTON, LC GERMAN, PS ROVNER, BW BRANT, LJ AF BURTON, LC GERMAN, PS ROVNER, BW BRANT, LJ TI PHYSICAL RESTRAINT USE AND COGNITIVE DECLINE AMONG NURSING-HOME RESIDENTS SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID ALZHEIMERS-DISEASE; EFFECTS MODELS; MORTALITY AB Objective: This study investigated the association between physical restraint use and decline in cognition. Design: Cohort analytic study describing changes in resident characteristics. Setting: Eight nursing homes, both urban and suburban, operated by a proprietary corporation in a large metropolitan area. Participants: 437 nursing home admissions, with 201 remaining at 1 year. Main Outcome Measures: Cognitive status was measured by geropsychiatrists, using the Folstein Mini-Mental State Exam, during a psychiatric evaluation of the resident. Daily restraint use was documented from nursing orders. Observations were made at 2 weeks, 10 weeks, and 1 year. Results: Restraint use alone and in combination with neuroleptic use was associated with poor cognition. Other variables associated with poor cognitive scores were: ADL impairment, poor adaptive behavior, and longer time in the nursing home. The use of neuroleptics alone was not significant. Variables which were associated with good cognitive status were: being non-ambulatory but without dementia and having strong social support. Conclusions: These findings raise the possibility that restraint use may contribute to cognitive impairment, specifically among residents who have moderate to no cognitive impairment at admission; however, the findings do not exclude an alternative explanation that residents undergoing cognitive decline are more likely to be put in restraints. Further research is needed to understand whether factors which can be manipulated contribute to cognitive decline. C1 THOMAS JEFFERSON UNIV,SCH MED,DEPT PSYCHIAT & HUMAN BEHAV,PHILADELPHIA,PA 19107. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP BURTON, LC (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,CTR HLTH SERV RES & DEV,624 N BROADWAY,BALTIMORE,MD 21205, USA. FU NIA NIH HHS [AG06765] NR 35 TC 47 Z9 47 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 1992 VL 40 IS 8 BP 811 EP 816 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA JH344 UT WOS:A1992JH34400010 PM 1353084 ER PT J AU BURG, MB GARCIAPEREZ, A AF BURG, MB GARCIAPEREZ, A TI HOW TONICITY REGULATES GENE-EXPRESSION SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE HYPERTONICITY; ALDOSE REDUCTASE; BETAINE; INOSITOL; TAURINE; HEAT SHOCK ID HEAT-SHOCK FACTOR; RENAL MEDULLARY CELLS; ALPHA-B-CRYSTALLIN; MESSENGER-RNA; MOLECULAR-CLONING; ALDOSE REDUCTASE; XENOPUS-OOCYTES; OSMOTIC-STRESS; INDUCTION; NACL AB The expression of a number of different mammalian genes is directly affected by hypertonicity. At present, the list of their products includes aldose reductase, heat shock proteins, early response factors, and transporters for betaine, inositol, and taurine. Hypertonicity increases the abundance of the mRNAs for all of them. Aldose reductase mRNA levels increase because of increased transcription with little change in the stability of its mRNA. Transcription of the betaine transporter also increases. The mechanisms by which hypertonicity increases the transcription of these mammalian genes remain speculative. However, the consideration of transcriptional control of betaine transport in bacteria and of heat shock proteins in many organisms provides interesting insight into this question. RP BURG, MB (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BLDG 10,ROOM GN307,BETHESDA,MD 20892, USA. NR 37 TC 47 Z9 47 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD AUG PY 1992 VL 3 IS 2 BP 121 EP 127 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA JK694 UT WOS:A1992JK69400001 PM 1391714 ER PT J AU SCHMIDT, K PESCE, C LIU, QZ NELSON, RG BENNETT, PH KARNITSCHNIG, H STRIKER, LJ STRIKER, GE AF SCHMIDT, K PESCE, C LIU, QZ NELSON, RG BENNETT, PH KARNITSCHNIG, H STRIKER, LJ STRIKER, GE TI LARGE GLOMERULAR SIZE IN PIMA-INDIANS - LACK OF CHANGE WITH DIABETIC NEPHROPATHY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE MORPHOMETRY; KIDNEY DISEASE OF DIABETES-MELLITUS; NATIVE AMERICANS; GLOMERULOSCLEROSIS; NON-INSULIN-DEPENDENT DIABETES-MELLITUS ID LONG-TERM; MELLITUS; KIDNEY; VOLUME; HYPERTROPHY; DISEASE; LESIONS; RAT; HYPERTENSION; PROGRESSION AB The mean glomerular volume, glomerular fraction of cortical volume, and percentage of obsolescent glomeruli were calculated in kidney specimens from autopsies on 34 Pima Indians, of whom 15 had noninsulin dependent diabetes mellitus and kidney disease of diabetes mellitus. These values were compared with those of black, white, and non-Pima native American individuals without diabetes mellitus. Glomerular volume in the Pima Indians was similar in the diabetic and nondiabetic subjects and significantly greater than in the white subjects. Black and non-Pima native American individuals had glomerular volumes intermediate between white individuals and Pima Indians. The mean glomerular volume was not affected by the number of obsolescent glomeruli in diabetic Pima Indians. The glomerular volume fraction was greater in the Pimas than in the other groups. These data showed that glomerular volume in the Pima Indians was significantly greater than that in white subjects. There was no difference between diabetic and nondiabetics Pimas, and glomerular size was not correlated with the presence or degree of glomerulosclerosis in this population. C1 NIDDKD,RENAL CELL BIOL SECT,BLDG 10,ROOM 3N110,BETHESDA,MD 20892. NIH,INTERINST GENET PROGRAM,BETHESDA,MD 20892. NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,PHOENIX,AZ. CLEVELAND CLIN FDN,DEPT BIOSTAT & EPIDEMIOL,PHOENIX,AZ. MARICOPA CTY MED EXAMINERS OFF,PHOENIX,AZ. RI Nelson, Robert/B-1470-2012 NR 31 TC 85 Z9 86 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD AUG PY 1992 VL 3 IS 2 BP 229 EP 235 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA JK694 UT WOS:A1992JK69400012 PM 1391722 ER PT J AU DIETER, MP BOORMAN, GA JAMESON, CW EUSTIS, SL URAIH, LC AF DIETER, MP BOORMAN, GA JAMESON, CW EUSTIS, SL URAIH, LC TI DEVELOPMENT OF RENAL TOXICITY IN F344 RATS GAVAGED WITH MERCURIC-CHLORIDE FOR 2 WEEKS, OR 2, 4, 6, 15, AND 24 MONTHS SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Article ID ZERO DOSE CONTROL; BROWN-NORWAY RAT; URINARY ENZYMES; LABORATORY RATS; MUTAGENICITY; EXCRETION; DAMAGE; ALPHA-2U-GLOBULIN; NEPHROTOXICITY; DERIVATIVES AB Both sexes of F344 rats were gavaged with maximal tolerated doses of mercuric chloride for periods from 2 wk to up to 2 yr to investigate chronic nephrotoxicity and potential carcinogenicity. The toxicity of mercuric chloride was excessive after 2 wk of exposure to doses ranging from 1.25 to 20 mg/kg, compromising renal function by selectively destroying cells of the proximal tubules, and eliciting marked elevations in urinary biomarker enzymes diagnostic for acute renal tubule necrosis. In the 2-wk studies, urinary alkaline phosphatase and aspartate aminotransferase were most sensitive to renal mercury toxicity among a panel of six enzymes, exhibiting twofold increases above controls at the 5.0 mg/kg dose, before changes in the other enzymes occurred. Urinary lactate dehydrogenase was the most responsive enzyme, with up to 11-fold increases in activity above controls. In response to mercuric chloride exposure of 5.0 mg/kg for 2-6 mo, the greatest and most persistent increases in elevation of urinary enzyme activities were exhibited by alkaline phosphatase and gamma-glutamyl transferase, which increased two- to threefold above controls. At this interval, the maximal severity of the renal lesions in both sexes of rats was graded as minimal to mild. Beyond 6 mo none of the urinary enzymes measured in this study was adequate as biomarkers of nephrotoxicity, although the severity of the renal lesions had progressed. Mercury accumulated in a dose-related fashion primarily in the kidney, and to a lesser extent in the liver The severity of the renal lesions was increased by continued exposure to mercuric chloride, as tissue concentrations of mercury rose in proportion to dose. Mercuric chloride treatment for 2 yr clearly exacerbated the severity of the spontaneous nephrotoxicity prevalent in aging F344 rats. The excessive mortality that occurred in the male rats was probably due to a combination of these factors. No renal tumors were detected in rats, possibly because the potential for their development was reduced; however direct tissue contact with mercury induced squamous-cell papillomas of the forestomach in both sexes. C1 PFIZER INC,GROTON,CT 06340. RP DIETER, MP (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 64 TC 20 Z9 20 U1 0 U2 2 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0098-4108 J9 J TOXICOL ENV HEALTH JI J. Toxicol. Environ. Health PD AUG PY 1992 VL 36 IS 4 BP 319 EP 340 PG 22 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA JJ880 UT WOS:A1992JJ88000004 PM 1354752 ER PT J AU OTT, D REIN, A AF OTT, D REIN, A TI BASIS FOR RECEPTOR SPECIFICITY OF NONECOTROPIC MURINE LEUKEMIA-VIRUS SURFACE GLYCOPROTEIN GP70SU SO JOURNAL OF VIROLOGY LA English DT Article ID NUCLEOTIDE-SEQUENCE; ENVELOPE GENE; AVIAN RETROVIRUSES; DETERMINANTS; INTERFERENCE; INFECTIVITY; DNA AB Murine leukemia viruses (MuLVs) initiate infection of NIH 3T3 cells by binding of the viral envelope (Env) protein to a cell surface receptor. Interference assays have shown that MuLVs can be divided into four groups, each using a distinct receptor: ecotropic, polytropic, amphotropic, and 10A1. In this study, we have attempted to map the determinants within viral Env proteins by constructing chimeric env genes. Chimeras were made in all six pairwise combinations between Moloney MCF (a polytropic MuLV), amphotropic MuLV, and 10A1, using a conserved EcoRI site in the middle of the Env coding region. The receptor specificity of each chimera was determined by using an interference assay. We found that amphotropic receptor specificity seems to map to the N-terminal portion of surface glycoprotein gp70su. The difference between amphotropic and 10A1 receptor specificity can be attributed to one or more of only six amino acid differences in this region. Nearly all other cases showed evidence of interaction between Env domains in the generation of receptor specificity. Thus, a chimera composed exclusively of MCF and amphotropic sequences was found to exhibit 10A1 receptor specificity. None of the chimeras were able to infect cells by using the MCF receptor; however, two chimeras containing the C-terminal portion of MCF gp70su could bind to this receptor, while they were able to infect cells via the amphotropic receptor. This result raises the possibility that receptor binding maps to the C-terminal portion of MCF gp70su but requires MCF N-terminal sequences for a functional interaction with the MCF receptor. RP OTT, D (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC VIROL & CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101] NR 22 TC 106 Z9 106 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 AUG PY 1992 VL 66 IS 8 BP 4632 EP 4638 PG 7 WC Virology SC Virology GA JF098 UT WOS:A1992JF09800002 PM 1321266 ER PT J AU LIU, JM GREEN, SW SHIMADA, T YOUNG, NS AF LIU, JM GREEN, SW SHIMADA, T YOUNG, NS TI A BLOCK IN FULL-LENGTH TRANSCRIPT MATURATION IN CELLS NONPERMISSIVE FOR B19 PARVOVIRUS SO JOURNAL OF VIROLOGY LA English DT Article ID 2 MESSENGER-RNAS; GENE-EXPRESSION; MINUTE VIRUS; NONSTRUCTURAL PROTEIN; P6 PROMOTER; 3' ENDS; INVITRO; MARROW; INFECTION; MICE AB Vertebrate parvoviruses share a similar genomic organization, with the capsid proteins encoded by genes on the right side and nonstructural proteins encoded by genes on the left side. The temporal and cell-specific appearances of these two types of gene products are regulated by a variety of genetic mechanisms. Rodent parvovirus structural proteins, for example, are encoded by a separate promoter which is positively regulated by nonstructural-gene products. In contrast, for the human B19 parvovirus, the analogous structural-gene promoter is nonfunctional, and both left- and right-side transcripts originate from a single promoter and are highly processed. Using a combination of sensitive RNA analyses of wild-type and mutant templates, we have found that the relative abundance of these alternatively processed transcripts appears to be governed by unique postinitiation events. In permissive cells, the steady-state level of right-side structural-gene transcripts predominates over that of left-side nonstructural-gene transcripts. In nonpermissive cells transfected with the B19 virus genome, nonstructural-gene transcripts predominate. Removal of 3' processing signals located in the middle of the viral genome increases transcription of the far right side. Disruption of a polyadenylation signal in this region makes readthrough of full-length right-side transcripts possible. These results suggest that the abundance of B19 virus RNAs is determined by active 3' processing and is coupled to DNA template replication. C1 NHLBI,CLIN HEMATOL BRANCH,BLDG 10,ROOM 7C103,BETHESDA,MD 20892. NR 34 TC 91 Z9 93 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 AUG PY 1992 VL 66 IS 8 BP 4686 EP 4692 PG 7 WC Virology SC Virology GA JF098 UT WOS:A1992JF09800009 PM 1385833 ER PT J AU BALDICK, CJ KECK, JG MOSS, B AF BALDICK, CJ KECK, JG MOSS, B TI MUTATIONAL ANALYSIS OF THE CORE, SPACER, AND INITIATOR REGIONS OF VACCINIA VIRUS INTERMEDIATE-CLASS PROMOTERS SO JOURNAL OF VIROLOGY LA English DT Article ID LATE MESSENGER-RNAS; LATE GENE-CLUSTER; TRANSCRIPTION FACTOR; FUNCTIONAL-ANALYSIS; EXPRESSION SYSTEM; POLY(A) SEQUENCES; DNA-REPLICATION; POLYMERASE; IDENTIFICATION; FRAGMENT AB Activation of vaccinia virus late gene transcription is dependent on DNA replication and the expression of three genes: A1L, A2L, and G8R (J. G. Keck, C. J. Baldick, Jr., and B. Moss, Cell 61:801-809,1990). To fully characterize the promoter elements of these trans-activator genes, we prepared more than 140 plasmid vectors containing natural and mutated DNA segments ligated to the Escherichia coli lacZ or chloramphenicol acetyltransferase reporter gene. Expression of the reporter genes occurred when the plasmids were transfected into vaccinia virus-infected cells and was enhanced when DNA replication was prevented, indicating that the AIL, A2L, and G8R promoters belong to the intermediate regulatory class. Deletional mutagenesis demonstrated that the regulatory elements of all three promoters extended between 20 and 30 nucleotides upstream of their RNA start sites. Single-base substitutions of the G8R promoter revealed two critical elements located from -26 to -13 (the core element) and -1 to +3 (the initiator element). Mutations in these regions drastically affected expression, as determined by beta-galactosidase and mRNA analyses. Additional mutations defined the TAAA sequence as the critical initiator element. The length, but not the nucleotide sequence, of the segment between the core and initiator regions was crucial. The requirement for the spacer to be 10 or 11 nucleotides was consistent with a single turn of a double helix. The AIL and A2L promoters resembled the G8R promoter, and mutations in the conserved bases had the predicted effects on expression. We concluded that the three intermediate promoters are composed of a 14-bp A+T-rich core sequence separated by one turn of the double helix from the TAAA initiator element. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 37 TC 65 Z9 65 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 AUG PY 1992 VL 66 IS 8 BP 4710 EP 4719 PG 10 WC Virology SC Virology GA JF098 UT WOS:A1992JF09800013 PM 1629951 ER PT J AU SHERMAN, G GOTTLIEB, J CHALLBERG, MD AF SHERMAN, G GOTTLIEB, J CHALLBERG, MD TI THE UL8 SUBUNIT OF THE HERPES-SIMPLEX VIRUS HELICASE-PRIMASE COMPLEX IS REQUIRED FOR EFFICIENT PRIMER UTILIZATION SO JOURNAL OF VIROLOGY LA English DT Article ID DNA-BINDING PROTEIN; TEMPERATURE-SENSITIVE MUTANTS; ESCHERICHIA-COLI; GENETIC-ANALYSIS; REPLICATION SYSTEM; POLYMERASE LOCUS; TYPE-1; RNA; IDENTIFICATION; PURIFICATION AB The herpes simplex virus (HSV) type 1 helicase-primase is a three-protein complex, consisting of a 1:1:l association of UL5, UL8, and UL52 gene products (J. J. Crute, T. Tsurumi, L. Zhu, S. K. Weller, P. D. Olivo, M. D. Challberg, E. S. Mocarski, and 1. R. Lehman, Proc. Natl. Acad. Sci. USA 86:2186-2189, 1989). We have purified this complex, as well as a subcomplex consisting of UL5 and UL52 proteins, from insect cells infected with baculovirus recombinants expressing the appropriate gene products. In confirmation of previous reports, we find that whereas UL5 alone has greatly reduced DNA-dependent ATPase activity, the UL5/UL52 subcomplex retains the activities characteristic of the heterotrimer. DNA-dependent ATPase activity, DNA helicase activity, and the ability to prime DNA synthesis on a poly(dT) template. We also found that the primers made by the subcomplex are equal in length to those synthesized by the UL5/UL8/UL52 complex. In an effort to uncover a role for UL8 in HSV DNA replication, we have developed a model system for lagging-strand synthesis in which the primase activity of the helicase-primase complex is coupled to the activity of the HSV DNA polymerase on ICP8-coated single-stranded M13 DNA. Using this assay, we found that the UL8 subunit of the helicase-primase is critical for the efficient utilization of primers; in the absence of UL8, we detected essentially no elongation of primers despite the fact that the rate of primer synthesis on the same template is undiminished. Reconstitution of lagging-strand synthesis in the presence of UL5/UL52 was achieved by the addition of partially purified UL8. Essentially identical results were obtained when Escherichia coli DNA polymerase I was substituted for the HSV polymerase/ULA2 complex. On the basis of these findings, we propose that UL8 acts to increase the efficiency of primer utilization by stabilizing the association between nascent oligoribonucleotide primers and template DNA. C1 NIAID,VIRAL DIS LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 46 TC 67 Z9 67 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 AUG PY 1992 VL 66 IS 8 BP 4884 EP 4892 PG 9 WC Virology SC Virology GA JF098 UT WOS:A1992JF09800033 PM 1321275 ER PT J AU LORI, F VERONESE, FD DEVICO, AL LUSSO, P REITZ, MS GALLO, RC AF LORI, F VERONESE, FD DEVICO, AL LUSSO, P REITZ, MS GALLO, RC TI VIRAL-DNA CARRIED BY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VIRIONS SO JOURNAL OF VIROLOGY LA English DT Article ID REVERSE-TRANSCRIPTASE; HTLV-III; SARCOMA VIRUS; CELL-LINES; T-CELLS; LYMPHOCYTES; RNA; REPLICATION; POLYMERASE; INFECTION AB A fundamental step in the replication of retroviruses is the reverse transcription of the viral RNA genome into a double-stranded DNA provirus. Retroviruses are believed to carry genomic information only as RNA, and synthesis of DNA is thought to start only after virus entry into the infected cell. We report here that infectious mature human immunodeficiency virus type 1 virions contain viral DNA of heterogeneous size. This heterogeneity seems to result from random stops of reverse transcription during minus- and plus-strand synthesis. The DNA carried by human immunodeficiency virus type 1 virions presumably originates from reverse transcription which takes place prior to or during formation of the mature virus particle. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. ADV BIOSCI LABS INC,KENSINGTON,MD 20895. NR 33 TC 177 Z9 179 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 AUG PY 1992 VL 66 IS 8 BP 5067 EP 5074 PG 8 WC Virology SC Virology GA JF098 UT WOS:A1992JF09800053 PM 1378514 ER PT J AU SCHEFFNER, M TAKAHASHI, T HUIBREGTSE, JM MINNA, JD HOWLEY, PM AF SCHEFFNER, M TAKAHASHI, T HUIBREGTSE, JM MINNA, JD HOWLEY, PM TI INTERACTION OF THE HUMAN PAPILLOMAVIRUS TYPE-16 E6 ONCOPROTEIN WITH WILD-TYPE AND MUTANT HUMAN P53 PROTEINS SO JOURNAL OF VIROLOGY LA English DT Note ID CARCINOMA CELL-LINES; RETINOBLASTOMA GENE-PRODUCT; TUMOR SUPPRESSOR GENE; SV40-TRANSFORMED CELLS; TRANSFORMED-CELLS; ANTIGEN; E7; DEGRADATION; ASSOCIATION; IDENTIFICATION AB The E6 oncoproteins encoded by the cancer-associated human papillomaviruses (HPVs) can associate with and promote the degradation of wild-type p53 in vitro. To gain further insight into this process, the ability of HPV-16 E6 to complex with and promote the degradation of mutant forms of p53 was studied. A correlation between binding and the targeted degradation of p53 was established. Mutant p53 proteins that bound HPV-16 E6 were targeted for degradation, whereas those that did not complex HPV-16 E6 were not degraded. Since the HPV-16 E6-promoted degradation involves the ubiquitin-dependent proteolysis pathway, specific mutations were made in the amino terminus of p53 to examine whether the E6 targeted degradation involved the N-end rule pathway. No requirement for destabilizing amino acids at the N terminus of p53 was found, nor was evidence found that HPV-16 E6 could provide this determinant in trans, indicating that the N-terminal rule pathway is not involved in the E6-promoted degradation of p53. C1 NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20892. UNIV TEXAS,SW MED CTR,SIMMONS CANC CTR,DALLAS,TX 75235. RP SCHEFFNER, M (reprint author), NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892, USA. RI Scheffner, Martin/K-2940-2012; Takahashi, Takashi/I-7262-2014 OI Scheffner, Martin/0000-0003-2229-0128; NR 48 TC 131 Z9 132 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 AUG PY 1992 VL 66 IS 8 BP 5100 EP 5105 PG 6 WC Virology SC Virology GA JF098 UT WOS:A1992JF09800058 PM 1321290 ER PT J AU FENG, YX YUAN, H REIN, A LEVIN, JG AF FENG, YX YUAN, H REIN, A LEVIN, JG TI BIPARTITE SIGNAL FOR READ-THROUGH SUPPRESSION IN MURINE LEUKEMIA-VIRUS MESSENGER-RNA - AN 8-NUCLEOTIDE PURINE-RICH SEQUENCE IMMEDIATELY DOWNSTREAM OF THE GAG TERMINATION CODON FOLLOWED BY AN RNA PSEUDOKNOT SO JOURNAL OF VIROLOGY LA English DT Note ID RIBOSOMAL FRAMESHIFTING SIGNAL; GENE AMBER CODON; NUCLEOTIDE-SEQUENCE; POL GENE; STOP CODON; TRANSLATION; READTHROUGH; UGA; POLYPEPTIDE; COMPONENT AB The pol gene of murine leukemia virus and other mammalian type C retroviruses is expressed by read-through suppression of an in-frame UAG codon which separates the gag and pol coding regions. In this study, we have analyzed the sequence requirements for read-through suppression by placing different portions of wild-type and mutant viral sequences from the gag-pol junction between reporter genes and testing transcripts of these constructs for suppression in reticulocyte lysates. We find that the read-through signal is contained within the first 57 nucleotides on the 3' side of the UAG codon. Our results indicate that the identities of six conserved bases in the eight-nucleotide, purine-rich sequence immediately downstream of the UAG codon are critical for suppression, as is the existence of a pseudoknot structure spanning the next 49 nucleotides. Thus, read-through suppression depends on a complex, bipartite signal in the mRNA. C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC VIROL & CARCINOGENESIS LAB,FREDERICK,MD 21702. RI Yuan, Hang/E-8670-2010 FU NCI NIH HHS [N01-CO-74101] NR 34 TC 68 Z9 68 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1992 VL 66 IS 8 BP 5127 EP 5132 PG 6 WC Virology SC Virology GA JF098 UT WOS:A1992JF09800063 PM 1629968 ER PT J AU WAGGIE, KS WUOWENS, J HOLLIFIELD, V HANSEN, CT AF WAGGIE, KS WUOWENS, J HOLLIFIELD, V HANSEN, CT TI LYMPHOBLASTIC LYMPHOMA IN A COLONY OF N-NIH(S)-BG-NU-XID MICE SO LABORATORY ANIMAL SCIENCE LA English DT Article AB During a 1-year period, 28 animals from a breeding colony of N:NIH(S)-bg-nu-xid mice were discovered to have rapidly enlarging subcutaneous swellings in the ventral, cervical, and axillary regions. Five of the mice also had hind limb paresis. Twenty-two of the mice were heterozygous nude females, five were homozygous nude males, and one was a homozygous nude female. All of the above mice were homo- or hemizygous for the beige and X-linked immunodeficiency mutations. The average age of the mice was 8.3 months. Generalized enlargement of the peripheral and internal lymph nodes was present at the time of necropsy examination. Other lesions commonly noted at necropsy included splenomegaly (15 mice), pale and thickened ventral lumbar spinal musculature (11 mice), and opaque, thickened meninges of the brain (10 mice). Histologic examination consistently disclosed infiltrates of neoplastic lymphoblasts in multiple tissues including lymph nodes, spleen, bone marrow, and meninges of the brain and spinal cord. The cells were positive for IgG on immunofluorescent staining, suggesting that the tumors were of B cell origin. The neoplasms observed in these mice have several similarities to tumors found in immunodeficient humans, suggesting that these mice may serve as useful animal models of lymphoma. C1 NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BETHESDA,MD 20892. NR 7 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 AUG PY 1992 VL 42 IS 4 BP 375 EP 377 PG 3 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA JL777 UT WOS:A1992JL77700009 PM 1434498 ER PT J AU GINSBERG, AM RAFFELD, M COSSMAN, J AF GINSBERG, AM RAFFELD, M COSSMAN, J TI MUTATIONS OF THE RETINOBLASTOMA GENE IN HUMAN LYMPHOID NEOPLASMS SO LEUKEMIA & LYMPHOMA LA English DT Article DE ANTIONCOGENE; LYMPHOMA; LEUKEMIA AB The inactivation or loss of tumor suppressor genes (anti-oncogenes) has been implicated as a mechanism central to the pathogenesis of many solid tumors. More recently, we and others have identified a role of one rumor suppressor gene, the retinoblastoma gene, in the development of human lymphoid lymphoma and leukemia. Here we review the involvement of the retinoblastoma gene in the control of normal lymphocyte cell division and the consequences of inactivation of the retinoblastoma gene for the development of lymphoid neoplasia. Our survey has disclosed a broad involvement of retinoblastoma gene inactivation in a wide variety of non-Hodgkin's lymphomas and lymphocytic leukemia. Based on these early findings, it appears likely that tumor suppressor genes may well be involved in many hematopoietic neoplasma. RP GINSBERG, AM (reprint author), NATL INST DIABET & DIGEST & KIDNEY DIS,CELLULAR & DEV BIOL LAB,BETHESDA,MD, USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD AUG PY 1992 VL 7 IS 5-6 BP 359 EP 362 DI 10.3109/10428199209049791 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA JV438 UT WOS:A1992JV43800003 PM 1493437 ER PT J AU MARTI, GE ZENGER, V BROWN, M MARTI, DM MELO, JV CRESCENZI, M DADEY, B HAN, T BERTIN, P CAPORASO, NE NOGUCHI, P AF MARTI, GE ZENGER, V BROWN, M MARTI, DM MELO, JV CRESCENZI, M DADEY, B HAN, T BERTIN, P CAPORASO, NE NOGUCHI, P TI ANTIGENIC EXPRESSION OF B-CELL CHRONIC LYMPHOCYTIC LEUKEMIC-CELL LINES SO LEUKEMIA & LYMPHOMA LA English DT Article DE B-CLL LEUKEMIC CELL LINES ANTIGENIC EXPRESSION AB A flow cytometric analysis of five B cell chronic lymphocytic leukemic (B-CLL) cell lines was undertaken using 129 unknown reagents from the blind panel (BP) and 72 reagents from the known CD panel obtained from the Fourth International Leucocyte Differentiation Conference and Workshop, B cell section (Vienna, 1989). The five cell lines examined were: SeD (PNAS 75, 5706, 1978), B-CLL-LCL (BLOOD 71, 9, 1988), JVM-HH and JVM-2(INT J CAN 38, 531, 1986), and WR # 1 (TH and BD). The reagents were # 1-129 (blinded panel) and reagents 1-44 and 53-84 (CD panel with CD23 reagents missing). Positivity was defined as greater than 30% of the cells having a three fold increase or more in mean channel fluorescence. Fourty-three reagents of the blinded panel were negative by these criteria while all remaining reagents were positive on all five lines. SeD showed the lowest reactivity; B-CLL-LCL and JVM-2 showed the most reactivity; JVM-HH and WR # 1 were intermediate. The known CD panel confirmed the reactivity of the blinded panel. An average immunophenotype was constructed and compared to published normal EBV lymphoblastoid cell lines and several differences were noted. There was an absence or significant decrease in the expression of CD19, CD21, CD22 and CD37 while there was an increased expression of CD38, CD54, CD74 and CD76. The heterogeneity observed between the B-CLL lines may in part be due to polymorphisms but is more likely to represent the underlying heterogeneity seen in common and familial B-CLL. In addition the variation in CD expression may be related to the effects of EBV transformation. RP MARTI, GE (reprint author), NIH,CELLULAR & MOLEC BIOL LAB,DIV BIOCHEM & BIOPHYS,CBER,FDA,BLDG 29,BETHESDA,MD 20892, USA. NR 0 TC 6 Z9 6 U1 0 U2 1 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD AUG PY 1992 VL 7 IS 5-6 BP 497 EP 504 DI 10.3109/10428199209049807 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA JV438 UT WOS:A1992JV43800019 PM 1337293 ER PT J AU GAGE, DA HUANG, ZH BENNING, C AF GAGE, DA HUANG, ZH BENNING, C TI COMPARISON OF SULFOQUINOVOSYL DIACYLGLYCEROL FROM SPINACH AND THE PURPLE BACTERIUM RHODOBACTER-SPHAEROIDES BY FAST-ATOM-BOMBARDMENT TANDEM MASS-SPECTROMETRY SO LIPIDS LA English DT Article AB Isolated sulfoquinovosyl-diacylglycerol (SQD) from spinach and the purple bacterium Rhodobacter sphaeroides provide two sources of very different molecular species of SQD. We were able to demonstrate by fast atom bombardment-collisionally activated dissociation tandem mass spectrometry in the negative ion mode that the sulfoquinovosyl head group of the plant and bacterial lipids can be characterized by the common fragmentation pattern found in the spectra of both samples. Differences in the acyl functions from the two sources were also identified by this technique. SQD specific fragments are found at m/z 299, 283, 241, 225, 165 and 80 which indicate the presence of the sulfoquinovosyl moiety. The two predominant molecular species found in spinach contain palmitic and linolenic ([M-H]- at m/z 815) or two linolenic acids ([M-H]- at m/z 837) in the sn-1 and sn-2 positions, while the two major species, of the bacterial lipid contain palmitic and 18:1 (vaccenic) acids ([M-H]- at m/z 819) or stearic and 18:1 (vaccenic) acids, ([M-H]- at m/z 847), respectively. C1 MICHIGAN STATE UNIV,DOE,PLANT RES LAB,E LANSING,MI 48824. RP GAGE, DA (reprint author), MICHIGAN STATE UNIV,NIH,DEPT BIOCHEM,MASS SPECTROMETRY FACIL,E LANSING,MI 48824, USA. FU NCRR NIH HHS [RR-00480] NR 19 TC 43 Z9 46 U1 0 U2 5 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 SN 0024-4201 J9 LIPIDS JI Lipids PD AUG PY 1992 VL 27 IS 8 BP 632 EP 636 DI 10.1007/BF02536123 PG 5 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA JH539 UT WOS:A1992JH53900012 PM 1406075 ER PT J AU BERGASA, NV BORQUE, MJ WAHL, LM RABIN, L JONES, EA AF BERGASA, NV BORQUE, MJ WAHL, LM RABIN, L JONES, EA TI MODULATION OF THIOACETAMIDE-INDUCED HEPATOCELLULAR NECROSIS BY PROSTAGLANDINS IS ASSOCIATED WITH NOVEL HISTOLOGIC-CHANGES SO LIVER LA English DT Article DE AMINOTRANSFERASE; BALLOONING; CYTOPROTECTION; FULMINANT HEPATIC FAILURE; HEPATOCELLULAR NECROSIS; PROSTAGLANDINS; RAT; THIOACETAMIDE AB Cytoprotective effects of the prostaglandins 16,16-dimethyl PGE2 (dmPGE2) and PGF2 alpha tromethamine (PGF2 alpha) were evaluated in the rat model of acute hepatocellular necrosis induced by thioacetamide (TAA). dmPGE2 (100 mug/kg SC 8 hourly) did not induce a significant increase in survival when started after the onset of TAA-induced fulminant hepatic failure. However, priming with dmPGE2 (100 mug/kg SC 30 min before TAA) reduced TAA-induced elevations in serum ALT (684 +/- 68 (SEM) vs 274 +/- 135 IU/l, p < 0.01). This phenomenon did not occur if dmPGE2 was administered after TAA or by the IP route. Modulation of TAA-induced centrizonal hepatocellular necrosis by dmPGE2 was associated with a striking increase in centrizonal ballooning of hepatocytes (p < 0.01), and, as assessed by stereology, less hepatocellular necrosis and degenerative changes. PGF2 alpha which in contrast to dmPGE2 does not act via cAMP, had no effect on TAA-induced changes in serum ALT or hepatic histology. These findings suggest that dmPGE2 decreases hepatocellular necrosis by activating surface membrane adenylate cyclase and consequently stimulating cAMP. Ballooning of hepatocytes could occur secondary to these membrane events and appears to be a marker of dmPGE2-induced cytoprotection in this model. RP BERGASA, NV (reprint author), NIDDKD,DIGEST DIS BRANCH,LIVER DIS SECT,BLDG 10,4-D 52,BETHESDA,MD 20892, USA. NR 0 TC 16 Z9 16 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0106-9543 J9 LIVER JI Liver PD AUG PY 1992 VL 12 IS 4 BP 168 EP 174 PN 1 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JQ566 UT WOS:A1992JQ56600003 PM 1406079 ER PT J AU LEVY, LA MURPHY, E RAJU, B LONDON, RE AF LEVY, LA MURPHY, E RAJU, B LONDON, RE TI SYNTHESIS AND EVALUATION OF FLUORINATED CALCIUM CHELATORS WITH ENHANCED RELAXATION CHARACTERISTICS SO MAGNETIC RESONANCE IN CHEMISTRY LA English DT Article DE F-19 NMR; FLUORINATED CALCIUM CHELATORS; ENHANCED RELAXATION CHARACTERISTICS ID INTRACELLULAR FREE CALCIUM; RED BLOOD-CELLS; F-19 NMR; SELECTIVE INVERSION; FREE MAGNESIUM; INDICATORS; LEAD AB The fluorinated calcium ion chelator 5F BAPTA [1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetra- acetic acid] was used for the determination of cytosolic Ca2+ ion levels in cells and tissues by F-19 NMR. The possibility of enhancing the sensitivity of these measurements by modifying the relaxation behavior of the chelator was evaluated. These strategies involved the design of a chelator with reduced T1 value viz. 5F RBAPTA {1,2-bis[2-amino-4-(1-carboxy-2-methyl-2-propyl)-5-fluorophenoxy]ethane-N,N,N',N'-tetraacetic acid), and the evaluation of a chelator with slower exchange characteristics, viz. 5F BenzEGTA [1-(2-amino-5-fluorophenoxy)-2-(2-aminoethoxy)ethane-N,N,N',N'-tetraacetic acid]. Both analogs exhibit chemical shift differences on calcium complexation which are similar to those of the parent compound, 5F BAPTA. In the case of BenzEGTA, a considerably greater pH dependence of the apparent calcium dissociation constant, K(D), also results from the presence of a tertiary amine with a pK value above the physiological range. Additionally, the synthetic approach used for RBAPTA can lead to a wide variety of derivatives with variable chemical, biochemical and NMR properties. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. NR 22 TC 4 Z9 4 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0749-1581 J9 MAGN RESON CHEM JI Magn. Reson. Chem. PD AUG PY 1992 VL 30 IS 8 BP 723 EP 732 DI 10.1002/mrc.1260300807 PG 10 WC Chemistry, Multidisciplinary; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA JF975 UT WOS:A1992JF97500006 ER PT J AU DANNER, DB AF DANNER, DB TI THE PROLIFERATION THEORY OF REJUVENATION SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE AGING; SENESCENCE; DAMAGE; REPAIR; EVOLUTION; HAYFLICK LIMIT ID FIBROBLASTS INVITRO; LIFE-SPAN; S-PHASE; CELLS; REPAIR; GROWTH; SENESCENCE; EXPRESSION; EVOLUTION; LONGEVITY AB A theory concerning the molecular basis of rejuvenation is presented that postulates a central role for cell proliferation. This theory assumes that aging is due to the accumulation of multiple forms of molecular damage and that rejuvenation is due to repair. The advantages of proliferation as a means of repair are described and it is proposed that cell proliferation is required for full rejuvenation. This proliferation theory offers several advantages: a different perspective on the question of which organisms age; an explanation of aging-related phenomena that are not well handled by traditional aging theories; a novel approach to alterating the aging rate; and testable implications for the design of new experimental systems and therapeutic interventions. RP DANNER, DB (reprint author), NIA,MOLEC GENET LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 71 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing. Dev. PD AUG PY 1992 VL 65 IS 1 BP 85 EP 107 DI 10.1016/0047-6374(92)90127-Y PG 23 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA JM510 UT WOS:A1992JM51000007 PM 1405792 ER PT J AU ENGELMANN, GL BOEHM, KD BIRCHENALLROBERTS, MC RUSCETTI, FW AF ENGELMANN, GL BOEHM, KD BIRCHENALLROBERTS, MC RUSCETTI, FW TI TRANSFORMING GROWTH FACTOR-BETA1 IN HEART DEVELOPMENT SO MECHANISMS OF DEVELOPMENT LA English DT Article DE TRANSFORMING GROWTH FACTOR-BETA; GENE EXPRESSION; MYOCYTE ID SPONTANEOUSLY HYPERTENSIVE RATS; NEONATAL CARDIOMYOCYTE DEVELOPMENT; FACTOR-BETA; CARDIAC MYOCYTES; MESSENGER-RNA; TGF-BETA; GENE-EXPRESSION; MUSCLE-CELLS; RIBONUCLEIC-ACID; EMBRYONIC HEART AB Defined biochemical stimuli regulating neonatal ventricular myocyte (cardiomyocyte) development have not been established. Since cardiomyocytes stop proliferating during the first 3-5 days of age in the rodent, locally generated 'anti-proliferative' and/or differentiation signals can be hypothesized. The transforming growth factor-beta (TGF-beta) family of peptides are multifunctional regulators of proliferation and differentiation of many different cell types. We have determined in neonatal and maturing rat hearts that TGF-beta-1 gene expression occurs in pups of both normotensive (Wistar Kyoto, WKY) and hypertrophy-prone rats (spontaneously hypertensive, SHR). TGF-beta-1, transcript levels were readily apparent in total ventricular RNA from SHR pups within 1 day of age and elevated in 3-7 day old WKY and SHR hearts when cardiomyocyte proliferation indices are diminished. TGF-beta-1 transcript levels remain at a 'relatively' high level throughout maturation and into adulthood in both strains. Further, TGF-beta-1, transcripts were localized to cardiomyocytes of neonatal rat ventricular tissue sections by in situ hybridization. Immunoreactive TGF-beta was co-localized to the intracellular compartment of neonatal cardiomyocytes at the light and electron microscopic level. In vitro analysis using primary cultures of fetal and neonatal cardiomyocytes indicated that TGF-beta-s inhibit mitogen stimulated DNA synthesis and thymidine incorporation. From these data, we propose that locally generated TGF-beta-s may act as autocrine and/or paracrine regulators of cardiomyocyte proliferation and differentiation as intrinsic components of a multifaceted biochemical regulatory process governing heart development. C1 CLEVELAND CLIN EDUC FDN,RES INST,DEPT HEART & HYPERTENS,CLEVELAND,OH 44106. NCI,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. CASE WESTERN RESERVE UNIV,DEPT REPROD BIOL,CLEVELAND,OH 44106. RP ENGELMANN, GL (reprint author), LOYOLA UNIV,STRITCH SCH MED,DEPT MED,RM 0370,2160 S 1ST AVE,MAYWOOD,IL 60153, USA. FU NHLBI NIH HHS [HL 42218] NR 66 TC 38 Z9 39 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD AUG PY 1992 VL 38 IS 2 BP 85 EP 98 DI 10.1016/0925-4773(92)90001-Z PG 14 WC Developmental Biology SC Developmental Biology GA JN569 UT WOS:A1992JN56900001 PM 1419851 ER PT J AU CALOGERO, AE NORTON, JA SHEPPARD, BC LISTWAK, SJ CROMACK, DT WALL, R JENSEN, RT CHROUSOS, GP AF CALOGERO, AE NORTON, JA SHEPPARD, BC LISTWAK, SJ CROMACK, DT WALL, R JENSEN, RT CHROUSOS, GP TI PULSATILE ACTIVATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS DURING MAJOR SURGERY SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; ZOLLINGER-ELLISON SYNDROME; TUMOR NECROSIS FACTOR; CORTISOL SECRETION; STIMULATED ADRENOCORTICOTROPIN; PLASMA ADRENOCORTICOTROPIN; HORMONE; STRESS; RAT; INTERLEUKIN-1 C1 NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N262,BETHESDA,MD 20892. NIH,CTR CLIN,BETHESDA,MD 20892. NIADDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. NR 35 TC 44 Z9 46 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD AUG PY 1992 VL 41 IS 8 BP 839 EP 845 DI 10.1016/0026-0495(92)90164-6 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JF817 UT WOS:A1992JF81700006 PM 1640860 ER PT J AU WEISS, JB VANKEULEN, H NASH, TE AF WEISS, JB VANKEULEN, H NASH, TE TI CLASSIFICATION OF SUBGROUPS OF GIARDIA-LAMBLIA BASED UPON RIBOSOMAL-RNA GENE SEQUENCE USING THE POLYMERASE CHAIN-REACTION SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE GIARDIA-LAMBLIA; GIARDIA; RIBOSOMAL RNA; POLYMERASE CHAIN REACTION; POLYMORPHISM ID ANTIGENIC VARIATION; AXENIC CULTURE; DNA; POLYMORPHISM; CHROMOSOMES; VARIANT; REPEAT; ARDEAE; PCR AB A sensitive and specific polymerase chain reaction-based assay has been developed to detect and analyze polymorphism in the Giardia lamblia 18S ribosomal RNA gene. Efficient amplification required the inclusion of cosolvents (glycerol and dimethyl sulfoxide) in the reaction. Following the optimization of conditions for amplification and subsequent hybridization of amplified product with radiolabeled oligonucleotide probe, a detection limit of less than one organism's worth of DNA was achieved. Thirty-five different G. lamblia strains obtained from various human and animal host types and geographic locations were analyzed by this method. The strains could be divided into 3 groups on the basis of defined nucleotide substitutions within the 183-bp amplified DNA fragment of the 18S ribosomal RNA gene. The groupings based upon the 18S ribosomal RNA gene sequence correlated with groupings previously assigned based upon patterns of surface antigens and restriction enzyme analysis. Analysis of the G. lamblia 18S ribosomal RNA gene sequences present in fecal specimens obtained from giardiasis patients revealed the presence of the different sequence types in these specimens. Some specimens contained more than one sequence type. The identification of subgroups of G. lamblia may facilitate studies of virulence, infectivity, and the epidemiology of giardia infection. C1 CLEVELAND STATE UNIV,DEPT BIOL,CLEVELAND,OH 44115. NIH,PARASIT DIS LAB,BETHESDA,MD 20892. RP WEISS, JB (reprint author), ROCHE MOLEC SYST,DEPT INFECT DIS,1145 ATLANTIC AVE,ALAMEDA,CA 94501, USA. NR 33 TC 75 Z9 77 U1 0 U2 7 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 AUG PY 1992 VL 54 IS 1 BP 73 EP 86 DI 10.1016/0166-6851(92)90096-3 PG 14 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA JF978 UT WOS:A1992JF97800008 PM 1518534 ER PT J AU CREEDON, KA KASLOW, DC RATHOD, PK WELLEMS, TE AF CREEDON, KA KASLOW, DC RATHOD, PK WELLEMS, TE TI IDENTIFICATION OF A PLASMODIUM-FALCIPARUM HISTONE 2A GENE SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Note DE HISTONE RNA; CHROMOSOME STRUCTURE; MALARIA ID MESSENGER-RNA; SEQUENCE C1 NIAID,MALARIA RES LAB,BETHESDA,MD 20892. US FDA,ROCKVILLE,MD. CATHOLIC UNIV AMER,WASHINGTON,DC 20064. FU NIAID NIH HHS [AI 26912] NR 13 TC 27 Z9 28 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 AUG PY 1992 VL 54 IS 1 BP 113 EP 115 DI 10.1016/0166-6851(92)90102-P PG 3 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA JF978 UT WOS:A1992JF97800014 PM 1518525 ER PT J AU SMEAL, T BINETRUY, B MERCOLA, D GROVERBARDWICK, A HEIDECKER, G RAPP, UR KARIN, M AF SMEAL, T BINETRUY, B MERCOLA, D GROVERBARDWICK, A HEIDECKER, G RAPP, UR KARIN, M TI ONCOPROTEIN-MEDIATED SIGNALING CASCADE STIMULATES C-JUN ACTIVITY BY PHOSPHORYLATION OF SERINE-63 AND SERINE-73 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN-KINASE; ONCOGENES; TRANSCRIPTION; TRANSDUCTION; ACTIVATION; FIBROBLASTS; GENES; TRANSFORMATION; COOPERATION; EXPRESSION AB In resting cells, c-Jun is phosphorylated on five sites. Three of these sites reside next to its DNA binding domain and negatively regulate DNA binding. In response to expression of oncogenic Ha-Ras, phosphorylation of these sites decreases, while phosphorylation of two other sites within c-Jun's activation domain is greatly enhanced. Phosphorylation of these residues, serines 63 and 73, stimulates the transactivation function of c-Jun and is required for oncogenic cooperation with Ha-Ras. We now show that the same changes in c-Jun phosphorylation are elicited by a variety of transforming oncoproteins with distinct biochemical activities. These oncoproteins, v-Sis, v-Src, Ha-Ras, and Raf-1, participate in a signal transduction pathway that leads to increased phosphorylation of serines 63 and 73 on c-Jun. While oncogenic Ha-Ras is a constitutive stimulator of c-Jun activity and phosphorylation, the normal c-Ha-Ras protein is a serum-dependent modulator of c-Jun's activity. c-Jun is therefore a downstream target for a phosphorylation cascade involved in cell proliferation and transformation. C1 UNIV CALIF SAN DIEGO,SCH MED,DEPT PHARMACOL,LA JOLLA,CA 92093. NCI,FREDERICK CANC RES FACIL,VIRAL CARCINOGENESIS LAB,VIRAL PATHOL LAB,BETHESDA,MD 20892. UNIV CALIF SAN DIEGO,SCH MED,DEPT BIOL,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,SCH MED,DEPT PATHOL,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,SCH MED,CTR MOLEC GENET,LA JOLLA,CA 92093. RI Binetruy, Bernard/A-6465-2009 FU NCI NIH HHS [CA50528]; NIEHS NIH HHS [ES04151] NR 38 TC 338 Z9 340 U1 2 U2 3 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 AUG PY 1992 VL 12 IS 8 BP 3507 EP 3513 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JE748 UT WOS:A1992JE74800022 PM 1630458 ER PT J AU ZHOU, RP DAAR, I FERRIS, DK WHITE, G PAULES, RS WOUDE, GV AF ZHOU, RP DAAR, I FERRIS, DK WHITE, G PAULES, RS WOUDE, GV TI PP39(MOS) IS ASSOCIATED WITH P34(CDC2) KINASE IN C-MOS(XE)-TRANSFORMED NIH 3T3-CELLS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MOS PROTO-ONCOGENE; MATURATION-PROMOTING FACTOR; CELL-CYCLE; XENOPUS OOCYTES; PROTOONCOGENE PRODUCT; MEIOTIC MATURATION; CDC2 PROTEIN; MEIOSIS-II; EGGS; COMPONENT AB We investigated the possible interactions between pp39mos and p34cdc2 kinase in NIH 3T3 cells transformed by c-mos(xe). pp39mos is coprecipitated with p34cdc2 when using either anti-PSTAIR antibody or p13suc1-Sepharose beads. Likewise, p34cdc2 is coprecipitated with pp39mos when using anti-mos antibody. However, pp39mos was not present in histone H1 kinase-active p34cdc2 complexes precipitated with anti-p34cdc2 C-terminal peptide antibody even during metaphase of the cell cycle. The molar ratio of p34 to pp39mos in the p13suc1 complex is approximately 2:1. Consistent with the tight association between pp39mos and tubulin, tubulin was also present in equivalent amounts with pp39mos and p34 in the p13suc1 complex. This pp39mos-p34cdc2-tubulin complex may be important in transformation by the mos oncogene. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,POB B,FREDERICK,MD 21702. NIEHS,MAMMALIAN MOLEC GENET GRP,RES TRIANGLE PK,NC 27709. NCI,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. OI Daar, Ira/0000-0003-2657-526X FU NCI NIH HHS [N01-CO-74101, N01-CO-74102] NR 41 TC 26 Z9 26 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 AUG PY 1992 VL 12 IS 8 BP 3583 EP 3589 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JE748 UT WOS:A1992JE74800031 PM 1321340 ER PT J AU DEY, A THORNTON, AM LONERGAN, M WEISSMAN, SM CHAMBERLAIN, JW OZATO, K AF DEY, A THORNTON, AM LONERGAN, M WEISSMAN, SM CHAMBERLAIN, JW OZATO, K TI OCCUPANCY OF UPSTREAM REGULATORY SITES INVIVO COINCIDES WITH MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I GENE-EXPRESSION IN MOUSE-TISSUES SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INTERFERON CONSENSUS SEQUENCE; HORMONE RECEPTOR SUPERFAMILY; DNA-BINDING SUBUNIT; C-FOS GENE; NF-KAPPA-B; TRANSCRIPTION FACTOR; NEGATIVE REGULATION; TRANSGENIC MICE; NUCLEOTIDE-SEQUENCE; RESPONSE ELEMENT AB The major histocompatibility complex (MHC) class I HLA-B7 transgene carrying a 660-bp upstream sequence is expressed in the mouse with tissue specificity that parallels that of the expression of endogenous mouse MHC class I (H-2) genes. We have performed in vivo genomic footprinting for the HLA-B7 transgene and the endogenous H-2K(b) gene. We show that the upstream region of both the transgene and the endogenous gene was extensively occupied in spleen tissue, where these genes are expressed at high levels. In contrast, no occupancy was detected in brain tissue, where expression of these genes is virtually absent. Sites exhibiting in vivo protection correspond to cis elements previously shown to bind to nuclear factors in vitro, including the constitutive enhancer region I and the interferon response element. The strongest tissue-specific protection was detected at site alpha, located downstream from the interferon response element. Site alpha bound a constitutively expressed nuclear factor(s) in vitro that exhibited an overlapping specificity which may involve a nuclear hormone receptor, RXR, and an AP-1-related factor. Site alpha was functional in vivo, as it enhanced MHC class I transcription in lymphocytes. These results show that the tissue-specific occupancy of the MHC class I regulatory sequences in vivo correlates with their expression and suggest that in vivo occupancy is controlled by a mechanism other than the mere presence of factors capable of binding to these sites. Our results suggest that a sequence present in the 660-bp upstream region in a human leukocyte antigen gene directs tissue-specific occupancy of MHC class I genes in vivo, independently of their position and copy number, illustrating a potential advantage of using a transgene for delimitation of the sequence requirement for in vivo occupancy. C1 NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892. YALE UNIV,SCH MED,HOWARD HUGHES SCHOLARS PROGRAM,NEW HAVEN,CT 06510. UNIV TORONTO,HOSP SICK CHILDREN,RES INST,TORONTO M5G 1X8,ONTARIO,CANADA. YALE UNIV,SCH MED,DEPT HUMAN GENET,NEW HAVEN,CT 06510. UNIV TORONTO,DEPT IMMUNOL,TORONTO M5S 1A1,ONTARIO,CANADA. NR 82 TC 80 Z9 80 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 AUG PY 1992 VL 12 IS 8 BP 3590 EP 3599 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JE748 UT WOS:A1992JE74800032 PM 1630463 ER PT J AU KARLS, U MULLER, U GILBERT, DJ COPELAND, NG JENKINS, NA HARBERS, K AF KARLS, U MULLER, U GILBERT, DJ COPELAND, NG JENKINS, NA HARBERS, K TI STRUCTURE, EXPRESSION, AND CHROMOSOME LOCATION OF THE GENE FOR THE BETA-SUBUNIT OF BRAIN-SPECIFIC CA2+/CALMODULIN-DEPENDENT PROTEIN KINASE-II IDENTIFIED BY TRANSGENE INTEGRATION IN AN EMBRYONIC LETHAL MOUSE MUTANT SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TISSUE-SPECIFIC EXPRESSION; MOLECULAR-CLONING; MESSENGER-RNAS; RAT-BRAIN; PURIFICATION; SEQUENCES; DOMAIN; ALPHA; MICE; MAP AB The transgenic mouse strain CAT40 carries in its germ line one copy of a DNA construct consisting of the chloramphenicol acetyltransferase gene and the immunoglobulin heavy-chain enhancer. We show that transgene integration has resulted in a recessive lethal mutation that leads to death of homozygous CAT40 embryos shortly after implantation. The transgene has integrated adjacent to the 3' end of the gene coding for the beta subunit of the brain-specific Ca2+/calmodulin-dependent protein kinase II (Camk-2). The complete cDNA sequence of the Camk-2 gene and most of its exon/intron structure was determined. The deduced amino acid sequence is highly homologous to the previously described rat protein. The chromosomal location of the Camk-2 locus was mapped by interspecific backcross analysis to the proximal region of mouse chromosome 11. This region lacks previously identified recessive embryonic lethal mutations. During embryonic development, Camk-2-specific transcripts are first seen in the head section of 12.5-day-old embryos, and in adult mice the gene is expressed almost exclusively in the brain. Although transcription of the Camk-2 gene in heterozygous CAT40 mice is affected by transgene integration, it is unlikely that this gene is responsible for the mutant phenotype, since it is not expressed in blastocysts and the first transcripts during normal development are detected after the death of homozygous CAT40 embryos. Transgene integration is accompanied by a large deletion of cellular DNA; death is therefore most likely caused by the loss of a gene or genes that are important for early postimplantation development. C1 UNIV HAMBURG,HEINRICH PETTE INST EXPTL VIROL & IMMUNOL,MARTINISTR 52,W-2000 HAMBURG 20,GERMANY. NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,MAMMALIAN GEN LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-7401] NR 37 TC 53 Z9 55 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 1992 VL 12 IS 8 BP 3644 EP 3652 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JE748 UT WOS:A1992JE74800038 PM 1321343 ER PT J AU BONDY, CA LEE, WH ZHOU, J AF BONDY, CA LEE, WH ZHOU, J TI ONTOGENY AND CELLULAR-DISTRIBUTION OF BRAIN GLUCOSE TRANSPORTER GENE-EXPRESSION SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID CYTOCHALASIN-B BINDING; RAT-BRAIN; DEVELOPMENTAL REGULATION; KETONE BODIES; BARRIER; FAMILY; GLUT-1; LIVER; CELLS RP BONDY, CA (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892, USA. NR 27 TC 84 Z9 85 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell Neurosci. PD AUG PY 1992 VL 3 IS 4 BP 305 EP 314 PG 10 WC Neurosciences SC Neurosciences & Neurology GA JF242 UT WOS:A1992JF24200005 PM 19912873 ER PT J AU DEUTCH, AY LEE, MC IADAROLA, MJ AF DEUTCH, AY LEE, MC IADAROLA, MJ TI REGIONALLY SPECIFIC EFFECTS OF ATYPICAL ANTIPSYCHOTIC-DRUGS ON STRIATAL FOS EXPRESSION - THE NUCLEUS-ACCUMBENS SHELL AS A LOCUS OF ANTIPSYCHOTIC ACTION SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID DOUBLE-BLIND MULTICENTER; LONG-TERM TREATMENT; C-FOS; BASAL GANGLIA; PREFRONTAL CORTEX; RAT STRIATUM; NEUROLEPTIC DRUGS; VENTRAL STRIATUM; DNA ELEMENT; HUMAN-BRAIN C1 DEPT VET AFFAIRS MED CTR,W HAVEN,CT 06516. NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. RP DEUTCH, AY (reprint author), YALE UNIV,SCH MED,CONNECTICUT MENTAL HLTH CTR,DEPT PSYCHIAT,34 PK ST,NEW HAVEN,CT 06508, USA. NR 83 TC 202 Z9 203 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell Neurosci. PD AUG PY 1992 VL 3 IS 4 BP 332 EP 341 PG 10 WC Neurosciences SC Neurosciences & Neurology GA JF242 UT WOS:A1992JF24200008 PM 19912876 ER PT J AU GAGE, KL GILMORE, RD KARSTENS, RH SCHWAN, TG AF GAGE, KL GILMORE, RD KARSTENS, RH SCHWAN, TG TI DETECTION OF RICKETTSIA-RICKETTSII IN SALIVA, HEMOLYMPH AND TRITURATED TISSUES OF INFECTED DERMACENTOR-ANDERSONI TICKS BY POLYMERASE CHAIN-REACTION SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE PCR; RICKETTSIA; DERMACENTOR; TICK; ROCKY MOUNTAIN SPOTTED FEVER ID SPOTTED-FEVER GROUP; IXODES-DAMMINI TICKS; MONOCLONAL-ANTIBODIES; TYPHUS INFECTION; UNITED-STATES; DNA; IDENTIFICATION; SPECIMENS; VECTORS; FLEAS C1 NIAID,DEPT HLTH & HUMAN SERV,PUBL HLTH SERV,VECTORS & PATHOGENS LAB,HAMILTON,MT 59840. ROCKY MTN LABS,INTRACELLULAR PARASITES LAB,HAMILTON,MT 59840. NR 46 TC 22 Z9 23 U1 0 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD AUG PY 1992 VL 6 IS 4 BP 333 EP 341 DI 10.1016/0890-8508(92)90010-U PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA JK017 UT WOS:A1992JK01700010 PM 1528203 ER PT J AU Hoelzel, AR AF Hoelzel, A. R. TI Conservation genetics of whales and dolphins SO MOLECULAR ECOLOGY LA English DT Review DE cetaceans; conservation; molecular genetics; stock identity AB Whales and dolphins (cetaceans) are found in all the world's oceans and in some of the major rivers, yet little is known about the distribution and behaviour of many species. At the same time, cetaceans are under threat from a variety of pressures including direct and indirect takes, pollution, and competition for habitat and prey. To ensure their long-term survival it will be necessary to preserve genetic diversity through the identification and protection of differentiated populations, the assessment of variation within local populations, and through a better understanding of reproductive and dispersal behaviour. The application of molecular genetic techniques is helping to provide answers to some of these previously intractable questions. Early results suggest few consistent patterns. Obvious geographic boundaries correlate to genetic distance in some species, and not in others. Furthermore, morphological variation within species can be fairly extensive without correlating to genetic distance, or relatively minor between morphotypes that are as genetically distinct as some species. These examples emphasize the need for further study. C1 [Hoelzel, A. R.] Univ Cambridge, Dept Genet, Cambridge CB2 3EH, England. [Hoelzel, A. R.] Univ London Imperial Coll Sci Technol & Med, NERC, Ctr Populat Biol, Ascot SL5 7PY, Berks, England. RP Hoelzel, AR (reprint author), NCI, LVC, Ft Detrick, MD 21702 USA. NR 38 TC 9 Z9 10 U1 2 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0962-1083 EI 1365-294X J9 MOL ECOL JI Mol. Ecol. PD AUG PY 1992 VL 1 IS 2 BP 119 EP 125 DI 10.1111/j.1365-294X.1992.tb00163.x PG 7 WC Biochemistry & Molecular Biology; Ecology; Evolutionary Biology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology; Evolutionary Biology GA V00QK UT WOS:000206802300006 PM 1364271 ER PT J AU TSENG, LYH OOI, GT BROWN, AL STRAUS, DS RECHLER, MM AF TSENG, LYH OOI, GT BROWN, AL STRAUS, DS RECHLER, MM TI TRANSCRIPTION OF THE INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-2 GENE IS INCREASED IN NEONATAL AND FASTED ADULT-RAT LIVER SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID I IGF-I; MESSENGER-RNA; FETAL-RAT; TISSUE DISTRIBUTION; HEPATOMA-CELLS; CHOROID-PLEXUS; EXPRESSION; IDENTIFICATION; IGFBP-1; HORMONE AB The insulin-like growth factor-binding proteins (IGFBPs) are a family of proteins that specifically bind IGF-I and IGF-II, determine their bioavailability to tissues, and modulate their actions in target tissues. Levels of IGFBPs in plasma and IGFBP mRNAs in liver are highly regulated with developmental age and metabolic status. We now demonstrate that the increase in IGFBP-2 mRNA in fasted adult rat liver and in the liver of normal neonatal rats reflects an increased rate of transcription. When adult rats were fasted for 2-3 days, IGFBP-2 mRNA was increased in liver, but not in brain or kidney. The increase in hepatic IGFBP-2 mRNA was observed after only 1 day of fasting. Levels decreased by half after 6 h of refeeding and returned to their low starting values after 2 days of refeeding. Transcription-elongation experiments indicated that transcription of the IGFBP-2 gene was increased in fasted liver. The rate of transcription increased 9.2- +/- 3.5-fold for transcripts labeled in exon 1 and 6.6- +/- 2.4-fold for transcripts labeled in exons 2, 3, and 4, suggesting that fasting causes a uniform increase in the number of RNA polymerase II molecules along the length of the IGFBP-2 gene. We infer from these results that the regulation of IGFBP-2 gene transcription in fasting occurs at the level of initiation rather than elongation. IGFBP-2 gene transcription also was increased 3.8- +/- 1.2-fold (exon 1) and 2.9- +/- 0.9-fold (exons 2, 3, and 4) in nuclei from 2-day postnatal rat liver compared with adult rat liver, consistent with the greater abundance of IGFBP-2 mRNA in neonatal rat liver. C1 NIDDKD, MOLEC & CELLULAR ENDOCRINOL BRANCH, GROWTH & DEV SECT,BLDG 10,ROOM 8D-14, BETHESDA, MD 20892 USA. UNIV CALIF RIVERSIDE, DIV BIOMED SCI, RIVERSIDE, CA 92521 USA. UNIV CALIF RIVERSIDE, DEPT BIOL, RIVERSIDE, CA 92521 USA. FU NIDDK NIH HHS [DK-39739] NR 33 TC 40 Z9 40 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD AUG PY 1992 VL 6 IS 8 BP 1195 EP 1201 DI 10.1210/me.6.8.1195 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JL963 UT WOS:A1992JL96300003 PM 1383692 ER PT J AU OEDA, T LEE, YC DRISCOLL, WJ CHEN, HC STROTT, CA AF OEDA, T LEE, YC DRISCOLL, WJ CHEN, HC STROTT, CA TI MOLECULAR-CLONING AND EXPRESSION OF A FULL-LENGTH COMPLEMENTARY-DNA ENCODING THE GUINEA-PIG ADRENOCORTICAL ESTROGEN SULFOTRANSFERASE SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PREGNENOLONE-BINDING PROTEIN; ADRENAL-CORTEX; RAT-LIVER; SOLUBLE FRACTION; CDNA; AMPLIFICATION; PURIFICATION; LOCALIZATION; POLYMERASE; SEQUENCE AB Complementary DNA for the guinea pig adrenocortical estrogen sulfotransferase (EST) has been cloned and expressed. Oligonucleotides, based on amino acid sequences of the purified 34-kilodalton protein, were synthesized and used to generate a specific probe by polymerase chain reaction for screening a guinea pig adrenal cDNA library. The polymerase chain reaction rapid amplification of cDNA ends procedure was employed to obtain the 3' and 5' cDNA ends, and a full-length cDNA was constructed. The cloned cDNA consists of 1192 base pairs and encodes a protein of 296 amino acids with a calculated molecular mass of 35,161 daltons. A computer search of the protein data banks revealed significant homology with several sulfotransferases: 71% with bovine placental estrogen sulfotransferase, 52% with rat liver phenol sulfotransferase, 35% with rat liver hydroxysteroid sulfotransferase, and 36% with rat liver senescence marker protein 2. The EST cDNA was inserted into the pcDNA I eukaryotic expression vector and transfected into COS-7 cells. The successful expression of EST cDNA in COS-7 cells was ascertained by Western blot analysis using antibody generated against the protein used to obtain the original amino acid sequence. Additionally, the expressed protein was clearly functional. Only after transfection with EST cDNA was there detectable estradiol sulfotransferase activity in COS-7 cell cytosol. The expressed EST had a single pI of 6.4, whereas native guinea pig adrenocortical EST exhibits four primary charge isoforms. The majority of adrenocortical EST activity focuses as a broad bimodal band in the pH range of 6.6-6.2; additionally, three other discrete immunocross-reactive isoforms are present with pIs of 5.5, 5.4, and 5.2. Antibodies generated against each individual isoform cross-react with all the other isoforms and with the expressed protein. These isoforms were previously reported to be isomers of a pregnenolone-binding protein; however it is now evident that the isoforms and antibodies raised against them are EST specific. Under high stringency hybridization conditions, EST mRNA was only detected in the adrenal gland, where two mRNA species of 1.4 and 1.8 kilobases were evident; when low stringency conditions were used, a faint 1.4-kilobase band was also detected in the liver. Primer extension analysis revealed that the multiple mRNAs do not arise from differential transcription initiation sites, and genomic Southern blot analysis indicated that the multiple mRNAs arise from a single gene. C1 NICHHD, ENDOCRINOL & REPROD RES BRANCH, ADRENAL CELL BIOL SECT,BLDG 10,ROOM BI-L400, BETHESDA, MD 20892 USA. NICHHD, ENDOCRINOL & REPROD RES BRANCH, MOLEC STRUCT & PROT CHEM, BETHESDA, MD 20892 USA. NR 39 TC 67 Z9 69 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD AUG PY 1992 VL 6 IS 8 BP 1216 EP 1226 DI 10.1210/me.6.8.1216 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JL963 UT WOS:A1992JL96300006 PM 1406700 ER PT J AU JAKOWLEW, SB LECHLEIDER, R GEISER, AG KIM, SJ SANTACOLOMA, TA CUBERT, J SPORN, MB ROBERTS, AB AF JAKOWLEW, SB LECHLEIDER, R GEISER, AG KIM, SJ SANTACOLOMA, TA CUBERT, J SPORN, MB ROBERTS, AB TI IDENTIFICATION AND CHARACTERIZATION OF THE CHICKEN TRANSFORMING GROWTH FACTOR-BETA-3 PROMOTER SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID DEOXYRIBONUCLEIC-ACID CLONING; MESSENGER RIBONUCLEIC-ACID; TRANSCRIPTION FACTOR SP1; FACTOR-BETA; EMBRYO CHONDROCYTES; CHLORAMPHENICOL ACETYLTRANSFERASE; SYNERGISTIC ACTIVATION; EXPRESSION PATTERNS; GENE-EXPRESSION; MAMMALIAN-CELLS AB The promoter regions of the three mammalian transforming growth factor-beta genes (TGF-beta-s 1, 2, and 3) have been recently cloned and characterized. The sequences show little similarity, suggesting different mechanisms of transcriptional control of these genes. To study differences in transcriptional regulation of mammalian and avian TGF-beta, we have cloned and sequenced the 5'-flanking region of chicken TGF-beta-3. Characterization of this region showed a TATA box and cAMP-responsive element (CRE) and AP-2 binding site consensus sequences starting at 12 and 28 base pairs, respectively, upstream from the TATA box. Moreover, four additional AP-2-like sites, 10 binding sites for the transcription factor Sp1, as well as two AP-1-like sites were also identified. Except for 32 base pairs of identity centered around the TATA box and CRE site and four other relatively small regions of identity, the chicken TGF-beta-3 promoter was found to be structurally very different from the human TGF-beta-3 promoter. Promoter fragments were cloned into a chloramphenicol acetyltransferase reporter plasmid to study functional activity. Basal transcriptional activity of the promoter was regulated in quail fibrosarcoma QM7 cells and in human adenocarcinoma A375 cells by multiple upstream elements including the TATA, CRE, and AP-2 sites. As in the human TGF-beta-3 promoter, the CRE site showed activation by forskolin, an effect which could be shown by expression of TGF-beta-3 mRNA in cultured chicken and quail cells as well. Our results indicate a complex pattern of transcriptional regulation of the chicken TGF-beta-3 gene and suggest that differences in the regulation of expression of the genes for mammalian and avian TGF-beta-3 may result in part from the unique structure of their 5'-flanking regions. RP JAKOWLEW, SB (reprint author), NCI, CHEMOPREVENT LAB, BLDG 41, ROOM B902, BETHESDA, MD 20892 USA. NR 52 TC 12 Z9 13 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD AUG PY 1992 VL 6 IS 8 BP 1285 EP 1298 DI 10.1210/me.6.8.1285 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JL963 UT WOS:A1992JL96300014 PM 1406706 ER PT J AU WOODGATE, R SEDGWICK, SG AF WOODGATE, R SEDGWICK, SG TI MUTAGENESIS INDUCED BY BACTERIAL UMUDC PROTEINS AND THEIR PLASMID HOMOLOGS SO MOLECULAR MICROBIOLOGY LA English DT Review ID ESCHERICHIA-COLI K-12; DNA-REPAIR GENES; RECA PROTEIN; SALMONELLA-TYPHIMURIUM; SOS MUTAGENESIS; ULTRAVIOLET-LIGHT; UV MUTAGENESIS; CHEMICAL MUTAGENESIS; SEQUENCE-ANALYSIS; LEXA REPRESSOR AB The popular image of a world full of pollutants mutating DNA is only partly true since there are relatively few agents which can subtly and directly change base coding; for example, some alkylating agents alter guanine so that it pairs like adenine. Many more mutagens are less subtle and simply destroy coding altogether rather than changing it. Such mutagens include ultraviolet light, X-rays, DNA cross-linkers and other agents which make DNA breaks or large adducts. In Escherichia coli, mutagenesis by these agents occurs during a DNA repair process which increases cell survival but with an inherent possibility of changing the original sequence. Such mutagenic DNA repair is, in part, encoded by the E. coli umuDC operon. This article reviews the structure, function, regulation and evolution of the umuDC operon and similar genes found both in other species and on naturally occurring plasmids. C1 NATL INST MED RES, YEAST GENET LAB, MILL HILL, LONDON NW7 1AA, ENGLAND. NICHHD, VIRUSES & CELL BIOL SECT, BETHESDA, MD 20892 USA. NR 50 TC 86 Z9 86 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD AUG PY 1992 VL 6 IS 16 BP 2213 EP 2218 DI 10.1111/j.1365-2958.1992.tb01397.x PG 6 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA JJ447 UT WOS:A1992JJ44700001 PM 1406263 ER PT J AU CHUANG, DM GAO, XM PAUL, SM AF CHUANG, DM GAO, XM PAUL, SM TI N-METHYL-D-ASPARTATE EXPOSURE BLOCKS GLUTAMATE TOXICITY IN CULTURED CEREBELLAR GRANULE CELLS SO MOLECULAR PHARMACOLOGY LA English DT Article ID AMINO-ACID NEUROTOXICITY; PHARMACOLOGICAL CHARACTERIZATION; NMDA RECEPTOR; RAT-BRAIN; SURVIVAL; NEURONS; BINDING; DEPENDENCE; PROMOTES; CALCIUM AB Exposure of cultured cerebellar granule cells to glutamate results in a concentration-dependent (EC50 = 22.7 +/- 0.4-mu-M) and delayed (24-72 hr) neurotoxicity, which is blocked by the specific N-methyl-D-aspartate (NMDA) receptor antagonists 2-amino-5-phosphovalerate and MK-801 but is unaffected by the non-NMDA receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione and 6,7-dinitroquinoxaline-2,3-dione. Although glutamate toxicity in these cells is mediated by the NMDA subtype of glutamate receptor, pretreatment of cerebellar granule cells with subtoxic concentrations of NMDA markedly antagonizes the neurotoxic actions of glutamate, with an IC50 of 55 +/- 4-mu-M. The neuroprotective effect of NMDA requires a preincubation time of approximately 120 min to be fully manifested and does not require the presence of NMDA during glutamate exposure. These data demonstrate that NMDA receptors mediate both neurotoxicity and neuroprotection in cerebellar granule cells. Among four glutamate receptor agonists tested (NMDA, quisqualate, ibotenate, and kainate), only NMDA was able to provide a robust neuroprotection against glutamate toxicity. Quisqualate was neither neurotoxic nor neuroprotective, whereas ibotenate, which was nontoxic by itself, induced a small degree of neuroprotection. In contrast, kainate, which was neurotoxic to cerebellar granule cells, also provided considerable neuroprotection against glutamate toxicity. Because preincubation of cerebellar granule cells with NMDA fails to alter NMDA receptor-mediated phosphoinositide hydrolysis or the specific binding of [H-3]MK-801 to NMDA receptors, it appears that the neuroprotective effects of NMDA are not due to NMDA receptor desensitization. C1 NIMH,MOLEC PHARMACOL SECT,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. RP CHUANG, DM (reprint author), NIMH,MOLEC NEUROBIOL SECT,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,BETHESDA,MD 20892, USA. NR 23 TC 81 Z9 83 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 AUG PY 1992 VL 42 IS 2 BP 210 EP 216 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JJ616 UT WOS:A1992JJ61600007 PM 1355259 ER PT J AU LEONHARDT, S GOROSPE, E HOFFMAN, BJ TEITLER, M AF LEONHARDT, S GOROSPE, E HOFFMAN, BJ TEITLER, M TI MOLECULAR PHARMACOLOGICAL DIFFERENCES IN THE INTERACTION OF SEROTONIN WITH 5-HYDROXYTRYPTAMINE-1C AND 5-HYDROXYTRYPTAMINE-2 RECEPTORS SO MOLECULAR PHARMACOLOGY LA English DT Article ID PLEXUS EPITHELIAL-CELLS; 5-HT2 RECOGNITION SITES; CHOROID-PLEXUS; RADIOLIGAND BINDING; ACID DIETHYLAMIDE; H-3 KETANSERIN; RAT-BRAIN; PHOSPHATIDYLINOSITOL TURNOVER; ADRENERGIC-RECEPTOR; GUANYL NUCLEOTIDE AB 5-Hydroxytryptamine (5HT)1C and 5HT2 receptors appear to be closely related, from a molecular viewpoint, displaying similar second messenger systems and a high degree of sequence homology. However, there are striking differences in the interactions of 5HT with 5HT1C and 5HT2 receptors; 5HT is generally more potent in stimulating responses mediated through 5HT1C receptors than responses mediated through 5HT2 receptors. Also [H-3]5HT labels 5HT1C receptors and not 5HT2 receptors. In order to explore more fully the molecular rationale for these differences, radioligand binding studies were performed in rat, human, and porcine brain and choroid plexus tissues and in mammalian cells transfected with rat 5HT1C or 5HT2 receptors; second messenger studies (inositol phosphate accumulation) were performed in the transfected cells. The second messenger studies confirmed the approximately 10-fold higher potency of 5HT in stimulating intracellular responses through 5HT1C receptors (EC50 = 8.3 nM) than in stimulating intracellular responses through 5HT2 receptors (EC50 = 101 nM). An agonist radioligand selective for the 5HT1C and 5HT2 receptors, 2,5-dimethoxy-(4-[I-125]iodo)phenylisopropylamine, was used, as well as [H-2]5HT, [H-3]mesulergine (antagonist radioligand for 5HT1C receptors), and [H-3]ketanserin (antagonist radioligand for 5HT2 receptors). Computer-assisted analyses of the binding data revealed two agonist affinity states for the 5HT1C receptor. The agonist high affinity state of the receptor was modifiable by guanyl nucleotides. The proportion of agonist high affinity states, relative to the total receptor population, was approximately 10% for both receptors. The apparent higher affinity of 5HT for the radiolabeled 5HT1c receptors was due to the higher affinity 5HT displayed for the agonist low affinity state of the 5HT1C receptor, compared with the affinity of 5HT for the agonist low affinity state of the 5HT2 receptor. The correspondence between the higher affinity of 5HT for the agonist low affinity state of the 5HT1C receptor, relative to the 5HT2 receptor, and the higher potency of 5HT in stimulating 5HT1C responses indicates that 5HT interacts with the agonist low affinity state of the 5HT1C and 5HT2 receptors in initiating its biological effects. These observations indicate that guanine nucleotide-binding protein (G protein)-coupled receptors can exhibit high affinity for neurotransmitters in both the free receptor and the G protein-coupled states and that receptors exhibiting this property may represent a novel subfamily of G protein-coupled receptors. C1 UNION UNIV,DEPT PHARMACOL & TOXICOL,A136,47 NEW SCOTLAND AVE,ALBANY,NY 12208. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. FU NIMH NIH HHS [MH 40716] NR 36 TC 70 Z9 71 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 AUG PY 1992 VL 42 IS 2 BP 328 EP 335 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JJ616 UT WOS:A1992JJ61600023 PM 1355262 ER PT J AU LOCKHART, AMC PIEGORSCH, WW BISHOP, JB AF LOCKHART, AMC PIEGORSCH, WW BISHOP, JB TI ASSESSING OVERDISPERSION AND DOSE-RESPONSE IN THE MALE DOMINANT LETHAL ASSAY SO MUTATION RESEARCH LA English DT Article DE STATISTICAL METHODS; GERM-CELL MUTAGENESIS; HERITABLE DISEASE; LITTER EFFECT; MOUSE; EXTRA-BINOMIAL VARIABILITY; UNDER-DISPERSION; DOSE RESPONSE ANALYSIS ID BETA-BINOMIAL DISTRIBUTION; WEAK MUTAGENIC ACTIVITY; TOXICOLOGICAL EXPERIMENTS; LONGITUDINAL DATA; BINARY RESPONSE; LINEAR-MODELS; PROPORTIONS; MICE; REPRODUCTION; VARIABILITY AB In dominant lethal studies the primary variables of interest are typically expressed as discrete counts or proportions (e.g., live implants, resorptions, percent pregnant). Simple statistical sampling models for discrete data such as binomial or Poisson generally do not fit this type of data because of extra-binomial or extra-Poisson departures from variability predicted under these simple models. Extra-variability in the fetal response may originate from parental contributions. These can lead to over- or under-dispersion seen as, e.g., extra-binomial variability in the proportion response. Utilizing a large control database, we investigated the relative impact of extra-variability from male or female contributions on the endpoints of interest. Male-related effects did not seem to contribute to overdispersion in our database; female-related effects were, however, evidenced. Various statistical methods were considered to test for significant treatment differences under these forms of sampling variability. Computer simulations were used to evaluate these methods and to determine which are most appropriate for practical use in the evaluation of dominant lethal data. Our results suggest that distribution-free statistical methods such as a nonparametric permutation test or rank-based tests for trend can be recommended for use. C1 NIEHS,GBAT & BIOMATH BRANCH,POB 12233,RES TRIANGLE PK,NC 27709. COMP SCI CORP,RES TRIANGLE PK,NC. OI Piegorsch, Walter/0000-0003-2725-5604 NR 76 TC 21 Z9 21 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD AUG PY 1992 VL 272 IS 1 BP 35 EP 58 DI 10.1016/0165-1161(92)90007-9 PG 24 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA JJ791 UT WOS:A1992JJ79100005 PM 1380118 ER PT J AU LEHMANN, PF KHAZAN, U WU, LC WICKES, BL KWONCHUNG, KJ AF LEHMANN, PF KHAZAN, U WU, LC WICKES, BL KWONCHUNG, KJ TI KARYOTYPE AND ISOZYME PROFILES DO NOT CORRELATE IN KLUYVEROMYCES-MARXIANUS VAR MARXIANUS SO MYCOLOGICAL RESEARCH LA English DT Article ID CHROMOSOME LENGTH POLYMORPHISMS; YEAST GENUS KLUYVEROMYCES; CANDIDA-ALBICANS; ELECTROPHORETIC KARYOTYPES; COLLETOTRICHUM-GLOEOSPORIOIDES; CLASSIFICATION; REASSOCIATION; REVISION; PROTEIN AB Diverse karyotypes were found for Kluyveromyces marxianus var. marxianus (anamorph = Candida kefyr) when analysed by pulsed-field gel electrophoresis. Two classes were discernible. One class was represented by six or seven chromosome-sized bands ranging from 1000 to 2400 kbp, the other by 9-17 bands including both smaller and larger pieces of DNA. The isozyme and protein profiles of K. marxianus var. marxianus were distinct from those of K. lactis. Two strains, originally derived from the same isolate of K. marxianus var. marxianus, showed identical isozyme patterns but slightly differing karyotypes. For identification of K. marxianus var. marxianus, the isozyme profiles provide a more stable character than the electrophoretic karyotypes. C1 MED COLL OHIO,DEPT MED,TOLEDO,OH 43699. NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. RP LEHMANN, PF (reprint author), MED COLL OHIO,DEPT MICROBIOL,POB 10008,TOLEDO,OH 43699, USA. NR 33 TC 9 Z9 9 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0953-7562 J9 MYCOL RES JI Mycol. Res. PD AUG PY 1992 VL 96 BP 637 EP 642 PN 8 PG 6 WC Mycology SC Mycology GA JH972 UT WOS:A1992JH97200005 ER PT J AU DISTECHE, CM BRANNAN, CI LARSEN, A ADLER, DA SCHORDERET, DF GEARING, D COPELAND, NG JENKINS, NA PARK, LS AF DISTECHE, CM BRANNAN, CI LARSEN, A ADLER, DA SCHORDERET, DF GEARING, D COPELAND, NG JENKINS, NA PARK, LS TI THE HUMAN PSEUDOAUTOSOMAL GM-CSF RECEPTOR ALPHA-SUBUNIT GENE IS AUTOSOMAL IN MOUSE SO NATURE GENETICS LA English DT Article ID COLONY-STIMULATING FACTOR; HUMAN X-CHROMOSOME; AFFINITY INTERLEUKIN-5 RECEPTOR; Y-CHROMOSOME; EXPRESSION CLONING; 2ND SUBUNIT; INACTIVATION; REGION; PROTEIN; DNA AB The gene encoding the granulocyte macrophage colony stimulating factor receptor alpha-subunit (CSF2RA) has previously been mapped to the pseudoautosomal region of the human sex chromosomes. In contrast, we report that the murine locus, Csf2ra, maps to an autosome in the laboratory mouse. By in situ hybridization and genetic mapping, Csf2ra maps at telomeric band D2 of mouse chromosome 19. This first instance of a pseudoautosomal locus in human being autosomal in mouse, indicates incomplete conservation between the human and mouse X chromosomes and suggests that the genetic content of the pseudoautosomal region may differ between species of eutherian mammals due to chromosomal rearrangements. C1 UNIV WASHINGTON,DEPT GENET,SEATTLE,WA 98195. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. IMMUNEX CORP,SEATTLE,WA 98101. RP DISTECHE, CM (reprint author), UNIV WASHINGTON,DEPT PATHOL,SEATTLE,WA 98195, USA. NR 45 TC 66 Z9 66 U1 0 U2 1 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD AUG PY 1992 VL 1 IS 5 BP 333 EP 336 DI 10.1038/ng0892-333 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA JJ121 UT WOS:A1992JJ12100009 PM 1363815 ER PT J AU JAFFE, HA DANEL, C LONGENECKER, G METZGER, M SETOGUCHI, Y ROSENFELD, MA GANT, TW THORGEIRSSON, SS STRATFORDPERRICAUDET, LD PERRICAUDET, M PAVIRANI, A LECOCQ, JP CRYSTAL, RG AF JAFFE, HA DANEL, C LONGENECKER, G METZGER, M SETOGUCHI, Y ROSENFELD, MA GANT, TW THORGEIRSSON, SS STRATFORDPERRICAUDET, LD PERRICAUDET, M PAVIRANI, A LECOCQ, JP CRYSTAL, RG TI ADENOVIRUS-MEDIATED INVIVO GENE-TRANSFER AND EXPRESSION IN NORMAL RAT-LIVER SO NATURE GENETICS LA English DT Article ID ADULT-RAT; HUMAN ALPHA-1-ANTITRYPSIN; INSITU HYBRIDIZATION; DEFICIENT RABBITS; NUCLEAR-PROTEIN; THERAPY; TRANSPLANTATION; HEPATOCYTES; CELLS; DNA AB Replication deficient, recombinant adenovirus (Ad) vectors do not require target cell replication for transfer and expression of exogenous genes and thus may be useful for in vivo gene therapy in hepatocytes. In vitro, primary cultures of rat hepatocytes infected with a recombinant Ad containing a human alpha-1-antitrypsin cDNA (Ad-alpha-1AT) synthesized and secreted human alpha-1AT for 4 weeks. In rats, in vivo intraportal administration of a recombinant Ad containing the E coli lacZ gene, was followed by expression of beta-galactosidase in hepatocytes 3 days after infection. Intraportal infusion of Ad-alpha-1AT produced detectable serum levels of human alpha-1AT for 4 weeks. Thus, targeted gene expression has been achieved in the liver, albeit at low levels, suggesting that adenovirus vectors may be a useful means for in vivo gene therapy in liver disorders. C1 NHLBI,PULM BRANCH,BETHESDA,MD 20892. INST GUSTAVE ROUSSY,CNRS,UA 1301,F-94805 VILLEJUIF,FRANCE. NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. TRANSGENE SA,F-67082 STRASBOURG,FRANCE. NR 59 TC 416 Z9 418 U1 0 U2 5 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD AUG PY 1992 VL 1 IS 5 BP 372 EP 378 DI 10.1038/ng0892-372 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA JJ121 UT WOS:A1992JJ12100017 PM 1302034 ER PT J AU KISS, A AGUILERA, G AF KISS, A AGUILERA, G TI PARTICIPATION OF ALPHA-1-ADRENERGIC RECEPTORS IN THE SECRETION OF HYPOTHALAMIC CORTICOTROPIN-RELEASING HORMONE DURING STRESS SO NEUROENDOCRINOLOGY LA English DT Article DE CORTICOTROPIN-RELEASING HORMONE; CATECHOLAMINES; ALPHA-1-ADRENERGIC RECEPTOR; METHOXAMINE; PRAZOSIN; COLCHICINE; MEDIAN EMINENCE; IMMUNOHISTOCHEMISTRY ID ANGIOTENSIN-II RECEPTORS; PARAVENTRICULAR NUCLEUS; MEDIAN-EMINENCE; ADRENOCORTICOTROPIN SECRETION; IMMUNOCYTOCHEMICAL EVIDENCE; IMMUNOREACTIVE INNERVATION; IMMOBILIZATION STRESS; ADRENERGIC-MECHANISMS; SYNTHESIZING NEURONS; RAT HYPOTHALAMUS AB The role of alpha-1-adrenergic receptors in the secretion of corticotropin-releasing hormone (CRH) during stress was studied by immunohistochemical analysis of the CRH content of the median eminence (ME) after intracerebroventricular (icv) administration of the alpha-1-adrenergic agonist, methoxamine, or the antagonist, prazosin, in rats pretreated with colchicine. Immunohistochemical staining was performed by the peroxidase technique on 40-mu-m free-floating sections using a polyclonal antibody specific for CRH. In the first experimental model, rats were implanted with icv cannulae and adapted to the experimental conditions by daily handling and icv injection of artificial CSF. Colchicine (75-mu-g) was administered through the cannulae 6 h before the experiment, conditions in which axonal transport was blocked with little change in basal immunostaining. Two hours after immobilization stress or a single injection of methoxamine (100-mu-g, icv), there was a marked decrease in CRH immunoreactivity throughout the ME, reflecting release of the neuropeptide into the portal circulation. The decrease in CRH immunostaining following immobilization was largely prevented by icv injection of the alpha-1-adrenergic antagonist, prazosin. In the second experimental model, rats were sacrificed 48 h after icv colchicine injection, conditions in which colchicine acts as a stressor and causes marked depletion of irCRH from the ME. This chronic effect of colchicine was also partially prevented by administation of prazosin, 400-ng injection 5 min prior to colchicine, followed by a continuous icv minipump infusion of prazosin, indicating that alpha-1-adrenergic stimulation contributes to the action of colchicine. In addition, the increase in the number and immunodensity of CRH cell bodies in the paraventricular nucleus typically observed following 48 h colchicine treatment was markedly reduced by prazosin administration, suggesting that alpha-1-adrenergic stimulation causes an increase in peptide synthesis as well as release. These results indicate that central alpha-adrenergic mechanisms are an important component in the regulation of hypothalamic CRH secretion during stress. RP KISS, A (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, ENDOCRINE PHYSIOL SECT, BLDG 10, RM 10N262, BETHESDA, MD 20892 USA. NR 33 TC 78 Z9 78 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD AUG PY 1992 VL 56 IS 2 BP 153 EP 160 DI 10.1159/000126223 PG 8 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA JL107 UT WOS:A1992JL10700005 PM 1328915 ER PT J AU GRAFMAN, J LITVAN, I MASSAQUOI, S STEWART, M SIRIGU, A HALLETT, M AF GRAFMAN, J LITVAN, I MASSAQUOI, S STEWART, M SIRIGU, A HALLETT, M TI COGNITIVE PLANNING DEFICIT IN PATIENTS WITH CEREBELLAR ATROPHY SO NEUROLOGY LA English DT Article; Proceedings Paper CT 43RD ANNUAL MEETING OF THE AMERICAN ACADEMY OF NEUROLOGY CY APR, 1991 CL BOSTON, MA SP AMER ACAD NEUROL ID OLIVOPONTOCEREBELLAR ATROPHY; DYSFUNCTION; IMPAIRMENTS; DEMENTIA; SKILLS AB We compared the performance of 12 patients with cerebellar atrophy (CA) and 12 normal controls matched for age and education on the Tower of Hanoi, a nine-problem task that requires cognitive planning. CA patients performed significantly worse than controls on this task despite no difference in planning and between-move pause times. A reanalysis of the data using just the subgroup of patients with pure cerebellar cortical atrophy (CCA) (N = 9) replicated the above results and also showed that CCA patients had significantly increased planning times compared with controls. Neither age, sex, education level, severity of dementia, word fluency, response time, memory, nor visuomotor procedural learning predicted CA or CCA performance. This deficit in cognitive planning suggests a functional link between the cerebellum, basal ganglia, and the frontal lobe concerning specific cognitive processes. However, the exact role of the cerebellum in cognitive planning remains undetermined. C1 NINCDS,MED NEUROL BRANCH,MOTOR CONTROL SECT,BETHESDA,MD 20892. GEORGETOWN UNIV HOSP,DEPT NEUROL,WASHINGTON,DC 20007. RP GRAFMAN, J (reprint author), NINCDS,MED NEUROL BRANCH,COGNIT NEUROSCI SECT,BLDG 10,ROOM 5C422,BETHESDA,MD 20892, USA. OI Grafman, Jordan H./0000-0001-8645-4457; Litvan, Irene/0000-0002-3485-3445; Stewart, Mark/0000-0003-3785-1338 NR 30 TC 271 Z9 272 U1 1 U2 9 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG PY 1992 VL 42 IS 8 BP 1493 EP 1496 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA JH221 UT WOS:A1992JH22100010 PM 1641142 ER PT J AU MURPHY, D RAPOPORT, SI AF MURPHY, D RAPOPORT, SI TI PET SCANNING IN SCHIZOPHRENIA, A CRITICAL-EVALUATION - COMMENTARY ON THE CURRENT STATUS OF PET SCANNING WITH RESPECT TO SCHIZOPHRENIA SO NEUROPSYCHOPHARMACOLOGY LA English DT Note ID GLUCOSE-METABOLISM; BRAIN; DYSFUNCTION; DISORDER; DISEASE; RATES C1 NIA,NEUROSCI LAB,BLDG 10,ROOM 6C-103,BETHESDA,MD 20892. NR 32 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD AUG PY 1992 VL 7 IS 1 BP 59 EP 61 PG 3 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA JH063 UT WOS:A1992JH06300007 PM 1524656 ER PT J AU STROMBERG, C NAVERI, L SAAVEDRA, JM AF STROMBERG, C NAVERI, L SAAVEDRA, JM TI ANGIOTENSIN AT2 RECEPTORS REGULATE CEREBRAL BLOOD-FLOW IN RATS SO NEUROREPORT LA English DT Article DE ANGIOTENSIN-II RECEPTORS; CEREBRAL BLOOD FLOW; LASER-DOPPLER FLOWMETRY; PD 123319; RAT AB LARGE cerebral arteries have been reported to contain angiotensin receptors that are exclusively of the AT2 subtype. We measured the effect of the AT2 receptor selective ligand PD 123319 on cerebral blood flow (CBF) in rats, using laser-doppler flowmetry. PD 123319 (1-10 mg kg-1) dose-dependently inhibited the increase in CBF, when the blood pressure was increased by a norepinephrine infusion. However, PD 123319 did not alter baseline CBF at normal blood pressures. Therefore PD 123319 appears to interfere with the autoregulatory mechanisms of CBF. The participation of AT2 receptors in the regulation of CBF confirms a physiological role for this receptor subtype, and may give clues for future treatment of various cerebrovascular disorders. RP STROMBERG, C (reprint author), NIMH,CLIN SCI LAB,PHARMACOL SECT,BLDG 10,ROOM 2D-45,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 10 TC 34 Z9 34 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD AUG PY 1992 VL 3 IS 8 BP 703 EP 704 PG 2 WC Neurosciences SC Neurosciences & Neurology GA JL105 UT WOS:A1992JL10500013 PM 1520859 ER PT J AU CLIVER, SP GOLDENBERG, RL CUTTER, GR HOFFMAN, HJ COPPER, RL GOTLIEB, SJ DAVIS, RO AF CLIVER, SP GOLDENBERG, RL CUTTER, GR HOFFMAN, HJ COPPER, RL GOTLIEB, SJ DAVIS, RO TI THE RELATIONSHIPS AMONG PSYCHOSOCIAL PROFILE, MATERNAL SIZE, AND SMOKING IN PREDICTING FETAL GROWTH-RETARDATION SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID NORTH-AMERICAN WOMEN; LOW-BIRTH-WEIGHT; CIGARETTE-SMOKING; HEALTH BEHAVIORS; RISK-FACTORS; STRESS; PREGNANCY; DIET; GAIN AB Objective: We explored the relationships among measures of psychosocial well-being, maternal size, and smoking in predicting infant size at birth. Methods: Participants in this population-based cohort study were drawn from public health prenatal clinics in Jefferson County, Alabama during 1985-1988. Para 1 and 2 women were screened for 11 risk factors for low birth weight, including small stature, a previous low birth weight infant, and smoking. Results: Poor scores on five of six psychosocial scales, as well as on a combined profile, were associated with a significantly higher relative risk of fetal growth retardation (FGR) only in thinner women, defined as having a body mass index less than the median (relative risk [RR] 2.11, 95% confidence interval [CI] 1.47, 3.04). A significant association between the psychosocial profile and birth weight was demonstrated for thin women in a multivariate analysis adjusting for gestational age, race, infant sex, and smoking (P = .0003). The relationship remained significant when hypertension, alcohol and drug use, and weight gain were added to the model (P = .003). In women with a body mass index above the median, a poor psychosocial profile showed little association with FGR (RR 1.20, 95% CI 0.73, 1.98) and did not have a significant association with birth weight. A poor profile had a greater association with FGR in non-smokers (RR 2.04, 95% CI 1.29, 3.22) than in smokers (RR 1.4, 95% CI 0.95, 2.06). Conclusions: Greater pre-pregnancy weight for height appears to protect against the adverse effects of a poor psychosocial profile in a population of poor, primarily black women. In thinner women, both smoking and a poor psychosocial profile were associated with a substantially increased rate of FGR, indicating a subgroup of women who may receive greater benefits from intervention programs. C1 UNIV ALABAMA,DEPT OBSTET & GYNECOL,PERINATAL EPIDEMIOL UNIT,UNIV STN,BIRMINGHAM,AL 35233. UNIV ALABAMA,SCH PUBL HLTH,BIRMINGHAM,AL 35294. NICHHD,PREVENT RES PROGRAM,BETHESDA,MD 20892. FU NICHD NIH HHS [N01-HD-4-2811] NR 27 TC 69 Z9 70 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD AUG PY 1992 VL 80 IS 2 BP 262 EP 267 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA JE800 UT WOS:A1992JE80000021 PM 1635741 ER PT J AU KELLY, K DAVIS, P MITSUYA, H IRVING, S WRIGHT, J GRASSMANN, R FLECKENSTEIN, B WANO, Y GREENE, W SIEBENLIST, U AF KELLY, K DAVIS, P MITSUYA, H IRVING, S WRIGHT, J GRASSMANN, R FLECKENSTEIN, B WANO, Y GREENE, W SIEBENLIST, U TI A HIGH PROPORTION OF EARLY RESPONSE GENES ARE CONSTITUTIVELY ACTIVATED IN T-CELLS BY HTLV-I SO ONCOGENE LA English DT Article ID VIRUS TYPE-I; COLONY-STIMULATING FACTOR; LEUKEMIA-LYMPHOMA VIRUS; GROWTH-FACTORS ENCODES; DNA-BINDING PROTEINS; LONG TERMINAL REPEAT; ZINC FINGER PROTEIN; INTERLEUKIN-2 RECEPTOR; TRANS-ACTIVATION; TAX GENE AB Immortalization of T cells by HTLV-I is mediated by the X region of the virus and probably involves transactivation of cellular genes. We show that T cells transformed by HTLV-I constitutively express a high proportion of early response genes that are normally transiently induced following antigenic or mitogenic activation of T cells. Thus, HTLV-I-infected T cells display an `early activation' phenotype that is distinct from the gene expression pattern of continuously dividing T cells. Ten early response genes representing a diverse array of functional categories were assayed. Four DNA-binding proteins/transcription factors including the p50 subunit of NF-kappa-B were evaluated. A protein(s) encoded by the X region of HTLV-I appeared to contribute to up-regulated expression of most, if not all, of the early response genes. For those genes that could be assayed, increased transcriptional rates, but not substantial changes in mRNA half-life, were demonstrated in the presence of pX-encoded proteins, suggesting that the transcriptional transactivator, Tax, affects the induction or maintenance of transcription for these mitogen-inducible genes. Therefore, Tax may mimic or interact with a component(s) of the signal transduction pathway activated by antigen or mitogen treatment. These data demonstrate that early response genes, some of which probably play roles in initiating or maintaining cellular proliferation, are frequent targets of HTLV-I activation. C1 DUKE UNIV,MED CTR,HOWARD HUGHES MED INST,DURHAM,NC 27710. NCI,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. UNIV ERLANGEN NURNBERG,INST KLIN & MOLEK VIROL,W-8520 ERLANGEN,GERMANY. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT MICROBIOL & IMMUNOL,DURHAM,NC 27710. RP KELLY, K (reprint author), NCI,PATHOL LAB,BETHESDA,MD 20892, USA. NR 61 TC 43 Z9 43 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG PY 1992 VL 7 IS 8 BP 1463 EP 1470 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA JE813 UT WOS:A1992JE81300001 PM 1630809 ER PT J AU BRUGGEMAN, LA BURBELO, PD YAMADA, Y KLOTMAN, PE AF BRUGGEMAN, LA BURBELO, PD YAMADA, Y KLOTMAN, PE TI A NOVEL SEQUENCE IN THE TYPE-IV COLLAGEN PROMOTER BINDS NUCLEAR PROTEINS FROM ENGELBRETH-HOLM-SWARM TUMOR SO ONCOGENE LA English DT Article ID HEAD-TO-HEAD; BASEMENT-MEMBRANE; EXTRACELLULAR-MATRIX; TRANSCRIPTIONAL REGULATION; BIDIRECTIONAL PROMOTER; GENE-REGULATION; CHAIN; CELLS; IDENTIFICATION; ALPHA-1(IV) AB The production of extracellular matrix proteins is an important element of tumor formation, and alterations in matrix protein metabolism may be critical to the process of tumor metastasis. Abundant expression of type IV collagen, the major structural protein of the basement membrane, is characteristic of the Engelbreth-Holm-Swarm (EHS) mouse sarcoma. In the present study, we evaluated mechanisms of transcriptional regulation of type IV collagen genes by analysing nuclear factors that bind to the promoter region. Gel mobility-shift assays indicated that specific proteins from EHS tumor bound the promoter and generated several unique shift patterns. The specific sequences to which these proteins bound were determined using DNAase I protection assays. DNA-binding proteins protected two regions from DNAase I digestion. The first region was similar to a GC box, the binding site for the transcription factor Spl. The other footprint was a 30-bp region that contained the novel sequence motif, `CCCTCCC' present in several other extracellular matrix promoters. Nuclear extracts isolated from tissues that variably express type IV collagen bound to this protected sequence with distinctly different shift patterns. Furthermore, in highly expressing tissues, unlabeled oligonucleotides containing the `CCCTCCC' motif effectively inhibited nuclear protein binding with the entire promoter. Thus, it is likely that a novel protein or protein complex binds to these sequences. Furthermore, these sequences appear to be unique to the genes that encode basement membrane proteins, suggesting a specific role in their regulation. C1 NIH,DEV BIOL LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. RI Burbelo, Peter/B-1027-2009 NR 36 TC 24 Z9 24 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG PY 1992 VL 7 IS 8 BP 1497 EP 1502 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA JE813 UT WOS:A1992JE81300005 PM 1630813 ER PT J AU KIM, CM VOGEL, J JAY, G RHIM, JS AF KIM, CM VOGEL, J JAY, G RHIM, JS TI THE HIV TAT GENE TRANSFORMS HUMAN KERATINOCYTES SO ONCOGENE LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; EPIDERMAL LANGERHANS CELLS; NEOPLASTIC TRANSFORMATION; KAPOSIS-SARCOMA; VIRUS-INFECTION; AIDS; PSORIASIS; ONCOGENE; LESIONS; INVITRO AB Skin disorders are frequently seen in patients with the acquired immune deficiency syndrome (AIDS). Since many of these cutaneous manifestations are accompanied by an early onset of epidermal hyperplasia, the keratinocyte is a candidate for infection by the human immunodeficiency virus (HIV). We now report that the HIV tat gene, under the control of the viral long terminal repeat (LTR), can efficiently transform human keratinocytes in culture. Our finding suggests that this activity of the tat gene may be responsible for the epidermal hyperplasia that accompanies psoriasis and precedes the development of squamous cell and basal cell carcinomas in AIDS patients. C1 JEROME H HOLLAND LAB,VIROL,ROCKVILLE,MD 20855. NCI,CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. RI Jay, Gregory/C-6346-2013 FU NCI NIH HHS [CA53633] NR 33 TC 39 Z9 39 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG PY 1992 VL 7 IS 8 BP 1525 EP 1529 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA JE813 UT WOS:A1992JE81300008 PM 1630815 ER PT J AU ULLRICH, SJ MERCER, WE APPELLA, E AF ULLRICH, SJ MERCER, WE APPELLA, E TI HUMAN WILD-TYPE P53 ADOPTS A UNIQUE CONFORMATIONAL AND PHOSPHORYLATION STATE INVIVO DURING GROWTH ARREST OF GLIOBLASTOMA CELLS SO ONCOGENE LA English DT Article ID CELLULAR TUMOR-ANTIGEN; LARGE-T-ANTIGEN; MUTANT P53; SV40-TRANSFORMED CELLS; MONOCLONAL-ANTIBODIES; SUPPRESSOR PROTEIN; TRANSFORMED-CELLS; CYCLE CONTROL; EXPRESSION; GENE AB The wild-type (wt) human tumor-suppressor gene product, p53, and its mutant form have been analysed in an in vivo system in which the inducible expression of wt p53 results in growth arrest in the G1 phase of the cell cycle. Two major pools of p53 are detected after wt p53 expression by their differential reactivity with the p53 monoclonal antibodies PAb 421 and 1801 as well as the mutant and wt-specific monoclonal antibodies PAb 240 and 1620; one pool contains wt and mutant p53 and is characterized as having a mutant conformation, whereas the other pool contains only wt p53 with a wt conformation. As G1 arrest is entered, the amount of wt p53 associated with the mutant pool decreases, such that by 12 h free wt and mutant p53 are the - major pools. Two-dimensional gel analysis of the p53 pools revealed that free wt p53 is phosphorylated to a greater degree than mutant p53, which correlated with the loss of the PAb 421 epitope on wt p53. In summary, the ability of wt p53 to exert an antiproliferative effect correlates with the presence of a unique conformational state of wt p53 characterized by increased phosphorylation and the loss of both the PAb 421 epitope and association with mutant p53 pool, whereas mutant p53 is unable to assume this conformational state. C1 THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,PHILADELPHIA,PA 19107. RP ULLRICH, SJ (reprint author), NCI,CELL BIOL LAB,BLDG 37,RM 1B03,BETHESDA,MD 20892, USA. NR 52 TC 146 Z9 147 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG PY 1992 VL 7 IS 8 BP 1635 EP 1643 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA JE813 UT WOS:A1992JE81300021 PM 1630823 ER PT J AU SHAH, VP BEHL, CR FLYNN, GL HIGUCHI, WI SCHAEFER, H BARRY, BW CONNERS, DP EVANS, CC FRANZ, TJ GANS, EH KAIL, N KRUEGER, GG LEYDEN, J MAIBACH, HI MALICK, AW NACHT, S NG, S PECK, CC PERSHING, LK POTTS, RO POULSEN, BJ SCOTT, RC SEQEIRA, JA SHARMA, D SKELLY, JP WU, MS AF SHAH, VP BEHL, CR FLYNN, GL HIGUCHI, WI SCHAEFER, H BARRY, BW CONNERS, DP EVANS, CC FRANZ, TJ GANS, EH KAIL, N KRUEGER, GG LEYDEN, J MAIBACH, HI MALICK, AW NACHT, S NG, S PECK, CC PERSHING, LK POTTS, RO POULSEN, BJ SCOTT, RC SEQEIRA, JA SHARMA, D SKELLY, JP WU, MS TI PRINCIPLES AND CRITERIA IN THE DEVELOPMENT AND OPTIMIZATION OF TOPICAL THERAPEUTIC PRODUCTS SO PHARMACEUTICAL RESEARCH LA English DT Article C1 HOFFMANN LA ROCHE INC,PHARMACEUT RES & DEV,NUTLEY,NJ 07110. UNIV MICHIGAN,COLL PHARM,ANN ARBOR,MI 48109. UNIV UTAH,COLL PHARM,SALT LAKE CITY,UT 84112. CIRD GALDERMA,F-06565 VALBONNE,FRANCE. HASTINGS ASSOCIATE RES & DEV,WESTPORT,CT 06880. UNIV PENN,PHILADELPHIA,PA 19104. UNIV CALIF SAN FRANCISCO,DEPT DERMATOL,SAN FRANCISCO,CA 94143. ADV POLYMER SYST INC,DEPT RES & DEV,REDWOOD CITY,CA 94063. ORTHO PHARMACEUT CORP,RARITAN,NJ 08869. CYGNUS THERAPEUT SYST,REDWOOD CITY,CA 94063. SYNTEX RES,PALO ALTO,CA 94304. ICI PLC,CENT TOXIC LAB,ACUTE TOXIC SECT,MACCLESFIELD SK104TJ,CHESHIRE,ENGLAND. PHARMACEUT RES & DEV,KENILWORTH,NJ 07033. NICHHD,BETHESDA,MD 20892. UPJOHN CO,CONSUMER PROD DEV,KALAMAZOO,MI 49001. UNIFORMED SERV UNIV HLTH SCI,DIV CLIN PHARMACOL,BETHESDA,MD 20814. UNIV BRADFORD,SCH PHARM,BRADFORD BD7 1DP,W YORKSHIRE,ENGLAND. UNIV UTAH,HLTH SCI CTR,DEPT MED,DIV DERMATOL,SALT LAKE CITY,UT 84112. UNIV ARKANSAS MED SCI HOSP,DEPT DERMATOL,LITTLE ROCK,AR 72205. RP SHAH, VP (reprint author), US FDA,CTR DRUG EVALUAT & RES,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 0 TC 10 Z9 11 U1 0 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD AUG PY 1992 VL 9 IS 8 BP 1107 EP 1111 DI 10.1023/A:1015831201020 PG 5 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA JH555 UT WOS:A1992JH55500023 PM 1357648 ER PT J AU SUZUKI, T GEORGE, FR MEISCH, RA AF SUZUKI, T GEORGE, FR MEISCH, RA TI ETONITAZENE DELIVERED ORALLY SERVES AS A REINFORCER FOR LEWIS BUT NOT FISCHER 344 RATS SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE ETONITAZENE; ETONITAZENE REINFORCEMENT; OPIOID; ORAL ROUTE; DRUG CONCENTRATION; FIXED-RATIO SIZE; DRUG SELF-ADMINISTRATION; DRUG REINFORCEMENT; BEHAVIORAL GENETICS; GENETIC DIFFERENCES; LEWIS RATS; FISCHER 344 RATS ID FOOD-DEPRIVATION; RHESUS-MONKEYS; DRUG; BEHAVIOR; ETHANOL; ESTABLISHMENT; MAINTENANCE; DRINKING; STRAINS; WATER AB Oral etonitazene self-administration was systematically investigated in two inbred strains of rats, Lewis (LEW) and Fischer 344 (F344). For LEW rats, etonitazene maintained higher rates of lever pressing and was consumed in larger volumes than the water vehicle when the reinforcement schedule was fixed ratio (FR) 8. In contrast, with F344 rats responding did not systematically exceed water values at any etonitazene concentration. LEW rats also drank substantially more etonitazene than F344 rats, and at FR 8 only LEW rats showed the typical inverted U-shaped function between etonitazene concentration and number of responses. For the LEW strain, response rate increased as FR size increased from FR 1 to FR 2 and FR 4, but decreased at FR8. For the F344 strain, as FR size increased response rate showed small increases, but the response rates were far lower than those of the LEW strain. The results support the conclusion that etonitazene was an effective reinforcer for LEW but not F344 rats. These findings demonstrate genetic differences in opioid reinforcement of operant behavior and indicate that genotype can be an important determinant of whether etonitazene serves as a reinforcer. C1 UNIV TEXAS,HLTH SCI CTR,SCH MED,DEPT PSYCHIAT & BEHAV SCI,1300 MOURSUND,HOUSTON,TX 77030. HOSHI UNIV,SCH PHARM,DEPT PHARMACOL,SHINAGAWA KU,TOKYO 142,JAPAN. UNIV NEW MEXICO,CTR ALCOHOLISM SUBST ABUSE & ADDICT,DEPT PSYCHOL,ALBUQUERQUE,NM 87131. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. NIDA,ADDICT RES CTR,LEXINGTON,KY 40583. FU NIAAA NIH HHS [AA-07754, AA-06104, AA-06924] NR 43 TC 64 Z9 64 U1 2 U2 3 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 AUG PY 1992 VL 42 IS 4 BP 579 EP 586 DI 10.1016/0091-3057(92)90002-W PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA JF537 UT WOS:A1992JF53700002 PM 1355294 ER PT J AU SCHINDLER, CW ZHENG, JW TELLA, SR GOLDBERG, SR AF SCHINDLER, CW ZHENG, JW TELLA, SR GOLDBERG, SR TI PHARMACOLOGICAL MECHANISMS IN THE CARDIOVASCULAR EFFECTS OF METHAMPHETAMINE IN CONSCIOUS SQUIRREL-MONKEYS SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE METHAMPHETAMINE; CARDIOVASCULAR EFFECTS; ALPHA-ADRENOCEPTORS; BETA-ADRENOCEPTORS; DOPAMINE RECEPTORS; SQUIRREL MONKEYS ID COCAINE; AMPHETAMINE; HALOPERIDOL; SCH-23390 AB The effects of methamphetamine were studied on cardiovascular function in conscious squirrel monkeys. Methamphetamine (0.1-3.0 mg/kg,IV) produced a dose-dependent increase in blood pressure. Its effects on heart rate were more complex, with lower doses (0.1-0.3 mg/kg) producing increases in heart rate and higher doses (1.0-3.0 mg/kg) producing decreases. To determine the pharmacological mechanisms involved in methamphetamine's effects, a number of drugs were tested as pretreatments to an injection of 0.2 mg/kg methamphetamine. This dose produced the maximal heart rate increase. The alpha(1)-antagonist prazosin completely antagonized the effects of methamphetamine on blood pressure, while the nonselective beta-antagonist propranolol and beta(1)-selective antagonist atenolol completely antagonized the tachycardiac effect of methamphetamine. The dopaminergic antagonists SCH 23390 and haloperidol antagonized some of the cardiovascular effects of methamphetamine. These results indicate that the pressor and tachycardiac effects of methamphetamine are mediated via alpha(1)- and beta(1)-adrenoceptor mechanisms, respectively. Dopaminergic mechanisms are also involved in methamphetamine's cardiovascular effects. C1 UNIV MARYLAND,DEPT PHARMACOL & EXPTL THERAPEUT,BALTIMORE,MD 21201. GEORGETOWN UNIV,DEPT PHARMACOL,WASHINGTON,DC 20007. BEIJING MED UNIV,NATL INST DRUG DEPENDENCE,BEIJING,PEOPLES R CHINA. RP SCHINDLER, CW (reprint author), NIDA,ADDICT RES CTR,BEHAV PHARMACOL & GENET LAB,POB 5180,BALTIMORE,MD 21224, USA. NR 29 TC 24 Z9 25 U1 0 U2 2 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 AUG PY 1992 VL 42 IS 4 BP 791 EP 796 DI 10.1016/0091-3057(92)90031-A PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA JF537 UT WOS:A1992JF53700031 PM 1325059 ER PT J AU CROUCH, RK HAZARD, ES LIND, T WIGGERT, B CHADER, G CORSON, DW AF CROUCH, RK HAZARD, ES LIND, T WIGGERT, B CHADER, G CORSON, DW TI INTERPHOTORECEPTOR RETINOID-BINDING PROTEIN AND ALPHA-TOCOPHEROL PRESERVE THE ISOMERIC AND OXIDATION-STATE OF RETINOL SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID PIGMENT-EPITHELIUM; PHOTORECEPTORS; LIGHT; DARK AB Retinol decomposes rapidly into a number of products, including its aldehyde form, retinal, when introduced into buffer in phospholipid vesicles or ethanol. Interphotoreceptor retinoid-binding protein at low concentrations is found to protect retinol from isomerization and oxidation. The addition of alpha-tocopherol to either liposomes or an ethanolic-buffer solution also prevents decomposition. Neither of these agents interferes with the successful regeneration of pigment with 9-cis retinal in rod outer segment preparations or the restoration of sensitivity by retinoids in isolated rod photoreceptors. C1 NEI,VIS RES LAB,BETHESDA,MD 20892. MED UNIV S CAROLINA,DEPT PHARMACOL,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT PATHOL,CHARLESTON,SC 29425. RP CROUCH, RK (reprint author), MED UNIV S CAROLINA,DEPT OPHTHALMOL,CHARLESTON,SC 29425, USA. FU NEI NIH HHS [EY04939, EY07543] NR 22 TC 81 Z9 82 U1 0 U2 4 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 AUG PY 1992 VL 56 IS 2 BP 251 EP 255 DI 10.1111/j.1751-1097.1992.tb02154.x PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JC905 UT WOS:A1992JC90500015 PM 1502268 ER PT J AU KLEINSZANTO, AJP IIZASA, T MOMIKI, S GARCIAPALAZZO, I CAAMANO, J METCALF, R WELSH, J HARRIS, CC AF KLEINSZANTO, AJP IIZASA, T MOMIKI, S GARCIAPALAZZO, I CAAMANO, J METCALF, R WELSH, J HARRIS, CC TI A TOBACCO-SPECIFIC N-NITROSAMINE OR CIGARETTE-SMOKE CONDENSATE CAUSES NEOPLASTIC TRANSFORMATION OF XENOTRANSPLANTED HUMAN BRONCHIAL EPITHELIAL-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TOBACCO SMOKE; HUMAN CELLS; LUNG; BRONCHUS; CARCINOGENESIS ID GROWTH-FACTOR; HUMAN LUNG; P53 MUTATIONS; CARCINOGENESIS; FRACTIONS; 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE; 12-O-TETRADECANOYL-PHORBOL-13-ACETATE; ADENOCARCINOMA; METABOLISM; INVITRO AB Using a xenotransplantation system in which immortalized nontumorigenic human bronchial epithelial cells (BEAS-2B cells) are grown in deepithelialized rat tracheas that are subcutaneously transplanted into athymic nude mice, we exposed BEAS-2B cells either to cigarette smoke condensate or to the tobacco-specific N-nitrosamine 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone. After 6 mo the carcinogen-exposed BEAS-2B cells were neoplastically transformed to invasive adenocarcinomas. Cell lines obtained from xenografts exposed in vivo to chemicals exhibited several features typical of malignant lung cancer cells, such as increased in vivo invasiveness that correlated well with enhanced type IV collagenolytic activity, resistance to serum-induced growth inhibition, and increased expression of transforming growth factor a and its cellular-membrane receptor. Invasiveness, similar to that seen after exposure to phorbol esters, was also detected after in vitro exposure of BEAS-2B cells to cigarette smoke condensate. Collectively, these data indicate that cigarette smoke condensate and N-nitrosamine 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone induce in vivo phenotypic changes in BEAS-2B cells similar to the progressive changes that occur during human lung carcinogenesis. C1 NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. RP KLEINSZANTO, AJP (reprint author), FOX CHASE CANC INST,DEPT PATHOL,PHILADELPHIA,PA 19111, USA. RI Klein-Szanto, Andres/E-6218-2010; Caamano, Jorge/I-6778-2012 OI Caamano, Jorge/0000-0003-3530-7056 FU NCI NIH HHS [CA06927, CA44981]; NCRR NIH HHS [RR05895] NR 35 TC 99 Z9 99 U1 0 U2 0 PU NATL ACAD PRESS 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 AUG 1 PY 1992 VL 89 IS 15 BP 6693 EP 6697 DI 10.1073/pnas.89.15.6693 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JF856 UT WOS:A1992JF85600007 PM 1323115 ER PT J AU KATZ, RA MACK, JPG MERKEL, G KULKOSKY, J ZHENG, G LEIS, J SKALKA, AM AF KATZ, RA MACK, JPG MERKEL, G KULKOSKY, J ZHENG, G LEIS, J SKALKA, AM TI REQUIREMENT FOR A CONSERVED SERINE IN BOTH PROCESSING AND JOINING ACTIVITIES OF RETROVIRAL INTEGRASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE RETROVIRAL DNA INTEGRATION; INVITRO INTEGRATION; INTEGRASE MUTATIONS ID MURINE LEUKEMIA-VIRUS; DNA-BINDING; CRYSTAL-STRUCTURE; VIRAL-DNA; PROTEIN; SEQUENCES; POL; RECOGNITION; INVITRO AB Retroviruses encode a protein, the integrase (IN), that is required for insertion of the viral DNA into the host cell chromosome. IN alone can carry out the integration reaction in vitro. The reaction involves endonucleolytic cleavage near the 3' ends of both viral DNA strands (the processing step), followed by joining of these new viral DNA ends to host DNA (the joining step). Based on their evolutionary conservation, we have previously identified at least 11 amino acid residues of IN that may be essential for the reaction. Here we report that even conservative replacements of one of these residues, an invariant serine, produce severe reductions in both the processing and joining activities of Rous sarcoma virus IN in vitro. Replacement of the analogous serine of the type 1 human immunodeficiency virus IN had similar effects on processing activity. These results suggest that this single conserved serine is a component of the active site and that one active site is used for both processing and joining. Replacement of this serine with certain amino acids resulted in a loss or reduction in DNA binding activities, while other replacements at this position appeared to affect later steps in catalysis. All of the defective Rous sarcoma virus INs were able to compete with the wild-type protein, which supports a model in which IN functions in a multimeric complex. C1 FOX CHASE CANC INST, INST CANC RES, 7701 BURHOLME AVE, PHILADELPHIA, PA 19111 USA. NCI, FREDERICK CANC RES & DEV CTR, CRYSTALLOG LAB, FREDERICK, MD 21702 USA. CASE WESTERN RESERVE UNIV, SCH MED, DEPT BIOCHEM, CLEVELAND, OH 44106 USA. FU NCI NIH HHS [CA47486, CA-06927, CA38046] NR 23 TC 27 Z9 27 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 AUG 1 PY 1992 VL 89 IS 15 BP 6741 EP 6745 DI 10.1073/pnas.89.15.6741 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JF856 UT WOS:A1992JF85600017 PM 1323118 ER PT J AU VIA, DP KEMPNER, ES PONS, L FANSLOW, AE VIGNALE, S SMITH, LC GOTTO, AM DRESEL, HA AF VIA, DP KEMPNER, ES PONS, L FANSLOW, AE VIGNALE, S SMITH, LC GOTTO, AM DRESEL, HA TI MOUSE MACROPHAGE RECEPTOR FOR ACETYLATED LOW-DENSITY-LIPOPROTEIN - DEMONSTRATION OF A FULLY FUNCTIONAL SUBUNIT IN THE MEMBRANE AND WITH PURIFIED RECEPTOR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CYSTEINE-RICH PROTEIN; BOVINE SERUM-ALBUMIN; RADIATION INACTIVATION; SIZE DETERMINATION; TARGET ANALYSIS; LDL RECEPTOR; RAT-LIVER; CHOLESTEROL; BINDING; ENZYMES AB The functional molecular mass of the macrophage receptor for acetylated low density lipoprotein (Ac-LDL) was determined in membranes by radiation inactivation analysis. Membranes from tumors induced by the mouse macrophage cell line P388D1 were frozen and irradiated with high-energy electrons. Residual binding activity indicated a minimum functional molecular mass of 35,000 Da, considerably smaller than the active 260,000 M(r) protein seen on ligand blots under nonreducing conditions. Scatchard analysis of receptor binding gave no evidence of partially inactivated molecules. The receptor protein, purified by affinity chromatography and preparative gel electrophoresis, was incubated with dithiothreitol (0.1-100 mM) and retested for binding activity. Active subunits of 158,000 and 80,000 M(r) could be demonstrated by ligand blotting, with quantitative conversion of binding activity to the 80,000 M(r) species at 10 mM dithiothreitol. At 100 mM dithiothreitol, all binding activity was lost. Further size reduction was not detected by silver staining. These data suggest that the isolated mouse macrophage Ac-LDL receptor is a trimer with one class of SH groups involved in trimerization and another in the actual binding site. The monomeric species is fully active in vitro under mild reducing conditions. The radiation inactivation data also suggest that each monomeric unit is fully active and capable of functioning independently in the binding of ligands in the membrane. C1 METHODIST HOSP,HOUSTON,TX 77030. NIAMSD,PHYS BIOL LAB,BETHESDA,MD 20892. BOEHRINGER MANNHEIM GMBH,DEPT ATHEROSCLEROSIS RES,W-6800 MANNHEIM 31,GERMANY. RP VIA, DP (reprint author), BAYLOR COLL MED,DEPT MED,6565 FANNIN ST,MS A601,HOUSTON,TX 77030, USA. FU NHLBI NIH HHS [HL-15648, HL-27341, HL-34111] NR 36 TC 15 Z9 15 U1 0 U2 0 PU NATL ACAD PRESS 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 AUG 1 PY 1992 VL 89 IS 15 BP 6780 EP 6784 DI 10.1073/pnas.89.15.6780 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JF856 UT WOS:A1992JF85600025 PM 1323119 ER PT J AU STEPIEN, PP MARGOSSIAN, SP LANDSMAN, D BUTOW, RA AF STEPIEN, PP MARGOSSIAN, SP LANDSMAN, D BUTOW, RA TI THE YEAST NUCLEAR GENE SUV3 AFFECTING MITOCHONDRIAL POSTTRANSCRIPTIONAL PROCESSES ENCODES A PUTATIVE ATP-DEPENDENT RNA HELICASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CONSERVED DODECAMER SEQUENCE; MESSENGER-RNA; SACCHAROMYCES-CEREVISIAE; PROTEIN; MUTATION; VAR1; EXPRESSION; GENOMES; DNA AB Mitochondrial gene expression is controlled largely through the action of products of the nuclear genome. The yeast nuclear gene suv3 has been implicated in a variety of mitochondrial posttranscriptional processes and in translation and, thus, represents a key control element in nuclear-mitochondrial interactions. We have exploited a property of a mutant allele of suv3, SUV3-1, that causes, among other effects, a massive increase in the abundance of excised group I introns to clone the wild-type gene by a strategy of colony Northern hybridization. We have determined that the 84-kDa deduced protein product of the suv3 gene, which maps to chromosome XVI, has a typical mitochondrial targeting presequence and additional sequence motifs that suggest that it belongs to a family of ATP-dependent RNA helicases, enzymes whose importance in post-transcriptional and translational events has recently become apparent. We have identified the SUV3-1 mutation as a G --> T transversion that creates a Val --> Leu substitution in a 10-amino acid block that is highly conserved among ATP-dependent RNA helicases. We discuss some implications of this mutation on the effects of the SUV3-1 allele on mitochondrial RNA metabolism. C1 UNIV TEXAS,SW MED CTR,DEPT BIOCHEM,DALLAS,TX 75235. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. RI Landsman, David/C-5923-2009; OI Landsman, David/0000-0002-9819-6675 FU NIGMS NIH HHS [GM22525, GM08014] NR 33 TC 83 Z9 88 U1 0 U2 3 PU NATL ACAD PRESS 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 AUG 1 PY 1992 VL 89 IS 15 BP 6813 EP 6817 DI 10.1073/pnas.89.15.6813 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JF856 UT WOS:A1992JF85600032 PM 1379722 ER PT J AU EILAT, D KIKUCHI, GE COLIGAN, JE SHEVACH, EM AF EILAT, D KIKUCHI, GE COLIGAN, JE SHEVACH, EM TI SECRETION OF A SOLUBLE, CHIMERIC GAMMA-DELTA-T-CELL RECEPTOR IMMUNOGLOBULIN HETERODIMER SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE RECEPTOR ASSEMBLY; COS CELL TRANSFECTION; PROTEIN ENGINEERING ID ALPHA-BETA-HETERODIMERS; LYMPHOCYTES-T; ANTIGEN; REGION; RECOGNITION; SPECIFICITY; EXPRESSION; PROTEIN; IDENTIFICATION; CONSTANT AB Soluble derivatives of T-cell antigen receptors (TCRs) should prove invaluable for studying the interaction of these receptors with antigens and major histocompatibility complex molecules, for structural studies, and for the identification of unknown ligands. We have engineered chimeric proteins, containing the extracellular domains of the mouse V(gamma)1.1-C(gamma)4 and V(delta)6.2-C(delta) (V, variable; C, constant) TCR chains fused to the hinge region, CH2 (H, heavy), and CH3 domains of human IgG1 heavy chain, and expressed them by transient transfection in COS cells. We show here that TCR gamma-IgH and TCR delta-IgH chimeric chains are produced intracellularly in significant amounts, that the two chains can assemble correctly to form disulfide-linked, glycosylated heterodimers, and that a selective mechanism allows secretion of correctly paired receptor chains into the medium. Identity of the chimeric secreted TCR gamma-delta-IgH heterodimer was confirmed by immunoblot analysis using V(gamma)1-specific anti-peptide antiserum and immunoprecipitation analysis using the monoclonal antibody UC7, which is shown to be specific for the TCR delta-chain. In addition, the soluble TCR gamma-delta-IgH heterodimer can be immunoprecipitated with the anti-clonotypic monoclonal antibody F10/56, which suggests that the fusion protein likely has a structural conformation similar to that of the native TCR. The COS cell expression system may prove useful for the production of additional TCR-IgH fusion proteins. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. NIAID,BIOL RESOURCES BRANCH,BETHESDA,MD 20892. NR 36 TC 13 Z9 13 U1 0 U2 0 PU NATL ACAD PRESS 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 AUG 1 PY 1992 VL 89 IS 15 BP 6871 EP 6875 DI 10.1073/pnas.89.15.6871 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JF856 UT WOS:A1992JF85600044 PM 1495977 ER PT J AU BOYER, JC BEBENEK, K KUNKEL, TA AF BOYER, JC BEBENEK, K KUNKEL, TA TI UNEQUAL HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REVERSE-TRANSCRIPTASE ERROR RATES WITH RNA AND DNA TEMPLATES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE FIDELITY; MUTAGENESIS; REVERSE TRANSCRIPTION; RETROVIRUSES ID FIDELITY; REPLICATION; POLYMERASE; MECHANISM; ACCURACY; INVIVO; HIV-1 AB Sequence variation in the type 1 human immunodeficiency virus (HIV-1) results, in part, from inaccurate replication by reverse transcriptase. Although this enzyme is error-prone during synthesis in vitro with DNA templates, the fidelity of RNA-dependent DNA synthesis relevant to minus-strand replication in the virus life cycle has not been examined extensively. In the present study, we have developed a system to determine the fidelity of transcription and reverse transcription and have used it to compare the fidelity of DNA synthesis by the HIV-1 reverse transcriptase with RNA and DNA templates of the same sequence. Overall, fidelity was several-fold higher with RNA than with DNA. Sequence analysis of mutants generated with the two substrates revealed that differences in error rates were substantial for specific errors. Fidelity with RNA was >10-fold higher for substitution and minus-one nucleotide errors at five different homopolymeric positions. Because such errors likely result from template-primer slippage, this result suggest; that misaligned intermediates are formed and/or used less frequently with an RNA template-DNA primer than with a DNA template-DNA primer. The results also suggest that HIV-1 reverse transcriptase synthesis with an RNA template-DNA primer was error-prone during incorporation of the first two nucleotides, perhaps due to aberrant enzyme-substrate interactions as synthesis initiates. The unequal error rates with RNA and DNA templates suggest that mistakes during minus- and plus-strand DNA synthesis may not contribute equally to the mutation rate of HIV-1. The data also provide estimates of substitution and frameshift error rates during transcription by T7 RNA polymerase. C1 NIEHS, MOLEC GENET LAB, RES TRIANGLE PK, NC 27709 USA. NR 22 TC 118 Z9 118 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 AUG 1 PY 1992 VL 89 IS 15 BP 6919 EP 6923 DI 10.1073/pnas.89.15.6919 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JF856 UT WOS:A1992JF85600054 PM 1379727 ER PT J AU MCKNIGHT, RA SHAMAY, A SANKARAN, L WALL, RJ HENNINGHAUSEN, L AF MCKNIGHT, RA SHAMAY, A SANKARAN, L WALL, RJ HENNINGHAUSEN, L TI MATRIX-ATTACHMENT REGIONS CAN IMPART POSITION-INDEPENDENT REGULATION OF A TISSUE-SPECIFIC GENE IN TRANSGENIC MICE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE WHEY ACIDIC PROTEIN GENE; A-ELEMENTS; CHROMATIN; GENETIC DOMAINS; MAMMARY GLAND ID HIGH-LEVEL EXPRESSION; ACIDIC PROTEIN GENE; CHICKEN LYSOZYME; BITHORAX COMPLEX; IDENTIFICATION; BOUNDARIES; PROMOTER; DOMAINS; BINDING; CELLS AB Matrix-attachment regions (MARs) may function as domain boundaries and partition chromosomes into independently regulated units. We have tested whether MAR sequences from the chicken lysozyme locus, the so-called A-elements, can confer position-independent regulation to a whey acidic protein (WAP) transgene in mammary tissue of mice. In the absence of MARs, expression of WAP transgenes was observed in 50% of the lines, and regulation during pregnancy, during lactation, and upon hormonal induction did not mimic that of the endogenous WAP gene and varied with the integration site. In contrast, all 11 lines in which WAP transgenes were juxtaposed to MAR elements showed expression. Accurate position-independent hormonal and developmental regulation was seen in four out of the five lines analyzed. These results indicate that MARs can establish independent genetic domains in transgenic mice. C1 USDA ARS,BELTSVILLE,MD 20725. RP MCKNIGHT, RA (reprint author), NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20982, USA. NR 27 TC 242 Z9 243 U1 0 U2 1 PU NATL ACAD PRESS 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 AUG 1 PY 1992 VL 89 IS 15 BP 6943 EP 6947 DI 10.1073/pnas.89.15.6943 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JF856 UT WOS:A1992JF85600059 PM 1495984 ER PT J AU CHU, CC PAUL, WE MAX, EE AF CHU, CC PAUL, WE MAX, EE TI QUANTITATION OF IMMUNOGLOBULIN MU-GAMMA-1 HEAVY-CHAIN SWITCH REGION RECOMBINATION BY A DIGESTION CIRCULARIZATION POLYMERASE CHAIN-REACTION METHOD SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE IGG1; INTERLEUKIN-4; ISOTYPE ID B-CELLS; EXPRESSION; IGE; DNA; GENE AB B lymphocytes expressing surface IgM with or without IgD may switch to the expression of other isotypes (IgG, IgA, or IgE) in the course of immune responses. Analyses of genomic DNA from cloned myelomas and hybridomas have shown that the isotype switch is accompanied by a rearrangement characterized by deletion of DNA between the switch (S) region of the mu-gene and that associated with the new isotype, resulting in the formation of a composite S region. Measurement of this deletional rearrangement has been difficult in populations of normal B cells but would be useful for investigating the mechanism of the rearrangement and determining whether deletional rearrangement is responsible for all instances of class switching. We have developed a sensitive assay for deletional rearrangement that we designate the digestion-circularization polymerase chain reaction (PCR). In this assay, genomic DNA is digested with a restriction enzyme that recognizes sites that flank the recombined composite S region. The digested DNA is then ligated at low concentrations to favor the formation of circles. The ligation joins the 5' and 3' ends of each restriction fragment, making it possible to amplify by PCR across the ligated restriction site by using appropriate primers. From DNA that has undergone deletional rearrangement, a single-sized PCR product is produced and can be quantitated. We demonstrate here that the digestion-circularization PCR assay can detect S-mu-S-gamma-1 rearrangements in B cells cultured with lipopolysaccharide and interleukin 4. The assay is sensitive enough to quantitate switched cells constituting only 1-2% of the population. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NR 21 TC 81 Z9 81 U1 0 U2 1 PU NATL ACAD PRESS 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 AUG 1 PY 1992 VL 89 IS 15 BP 6978 EP 6982 DI 10.1073/pnas.89.15.6978 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JF856 UT WOS:A1992JF85600066 PM 1495989 ER PT J AU FOX, DK PRESPER, KA ADHYA, S ROSEMAN, S GARGES, S AF FOX, DK PRESPER, KA ADHYA, S ROSEMAN, S GARGES, S TI EVIDENCE FOR 2 PROMOTERS UPSTREAM OF THE PTS OPERON - REGULATION BY THE CAMP RECEPTOR PROTEIN REGULATORY COMPLEX SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PHOSPHOENOLPYRUVATE, GLYCOSE PHOSPHOTRANSFERASE SYSTEM; SUGAR TRANSPORT; BACTERIAL TRANSCRIPTION ID BACTERIAL PHOSPHOTRANSFERASE SYSTEM; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; SUGAR-TRANSPORT; CRR GENES; ENZYME-I AB Several potential target sites for multiple regulatory mechanisms were previously identified in the 5' flanking region of the pts operon. We have investigated the in vitro interactions of the cAMP receptor protein (CRP).cAMP regulatory complex with two DNA binding sites, by gel mobility-shift assays, and report the analysis of the functional role of each of the binding sites in vivo. Promoter-reporter gene fusion studies identified two CRP.cAMP-dependent promoters (the previously identified P1 and another promoter, P0) upstream of ptsH. The crr promoters (P2) within ptsI may be negatively regulated by CRP.cAMP. C1 JOHNS HOPKINS UNIV,MCCOLLUM PRATT INST,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,DEPT BIOL,BALTIMORE,MD 21218. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM38759] NR 15 TC 25 Z9 26 U1 0 U2 0 PU NATL ACAD PRESS 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 AUG 1 PY 1992 VL 89 IS 15 BP 7056 EP 7059 DI 10.1073/pnas.89.15.7056 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JF856 UT WOS:A1992JF85600082 PM 1323126 ER PT J AU AHN, BY MOSS, B AF AHN, BY MOSS, B TI GLUTAREDOXIN HOMOLOG ENCODED BY VACCINIA VIRUS IS A VIRION-ASSOCIATED ENZYME WITH THIOLTRANSFERASE AND DEHYDROASCORBATE REDUCTASE ACTIVITIES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DISULFIDE REDUCTION; GLUTATHIONE; TRANSHYDROGENASE ID GLUTATHIONE-DEPENDENT SYNTHESIS; PIG-LIVER THIOLTRANSFERASE; AMINO-ACID-SEQUENCE; ESCHERICHIA-COLI; RIBONUCLEOTIDE REDUCTASE; RNA-POLYMERASE; DNA-REPLICATION; PURIFICATION; THIOREDOXIN; EXPRESSION AB Glutaredoxins (GRXs), also known as thioltransferases, use glutathione as a cofactor for reduction of disulfides in prokaryotes and eukaryotes. We demonstrate that the vaccinia virus O2L open reading frame encodes a functional GRX, as predicted by Johnson et al. [Johnson, G. P., Goebel, S. J., Perkus, M. E., Davis, S. W., Winslow, J. P. & Paoletti, E. (1991) Virology 181, 378-3811 from sequence homology. The 12-kDa protein product of the O2L open reading frame was synthesized after viral DNA replication, coincident with a major increase in cytoplasmic glutathione-dependent thioltransferase activity. The protein was associated with purified vaccinia virions and was not released by treatment with a nonionic detergent unless dithiothreitol was added. The virion-derived protein, as well as a recombinant form expressed in Escherichia coli, exhibited thioltransferase and dehydroascorbate reductase activities indicative of a functional GRX. The postreplicative synthesis of vaccinia virus GRX and its association with virions suggest that the enzyme may have novel roles in the virus growth cycle. RP AHN, BY (reprint author), NIAID, VIRAL DIS LAB, BETHESDA, MD 20892 USA. NR 43 TC 67 Z9 70 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 AUG 1 PY 1992 VL 89 IS 15 BP 7060 EP 7064 DI 10.1073/pnas.89.15.7060 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JF856 UT WOS:A1992JF85600083 PM 1496000 ER PT J AU ADAMS, JH SIM, BKL DOLAN, SA FANG, XD KASLOW, DC MILLER, LH AF ADAMS, JH SIM, BKL DOLAN, SA FANG, XD KASLOW, DC MILLER, LH TI A FAMILY OF ERYTHROCYTE BINDING-PROTEINS OF MALARIA PARASITES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PLASMODIUM; INVASION; ADHESINS; DUFFY BLOOD GROUP ANTIGEN; SIALIC ACID ID RECOMBINANT VACCINIA VIRUS; PLASMODIUM-FALCIPARUM; CIRCUMSPOROZOITE PROTEIN; ANTIGEN; KNOWLESI; MEROZOITES; INVASION; SURFACE; IDENTIFICATION; GLYCOPROTEIN AB Malaria erythrocyte binding proteins use the Duffy blood group antigen (Plasmodium vivax and Plasmodium knowlesi) and sialic acid (Plasmodium falciparum) on the erythrocyte surface as receptors. We had previously cloned the one P. vivax gene, the one P. falciparum gene, and part of one of the three P. knowlesi genes encoding these erythrocyte binding proteins and described the homology between the P. knowlesi and P. vivax genes. We have completed the cloning and sequencing of the three P. knowlesi genes and identified introns in the P. vivax and P. falciparum genes that correct the previously published deduced amino acid sequences. All have similar structures, with one or two exons encoding the signal sequence and the erythrocyte binding domain, an exon encoding the transmembrane domain, and two exons encoding the cytoplasmic domain with the exception of the P. knowlesi beta-gene. The regions of amino acid sequence homology among all the genes are the 5' and 3' cysteine-rich regions of the erythrocyte binding domain. On the basis of gene structure and amino acid homology, we propose that the Duffy binding proteins and the sialic acid binding protein are members of a gene family. The level of conservation (almost-equal-to 70%) of the deduced amino acid sequences in the 5' cysteine-rich region between the P. vivax protein and the three P. knowlesi proteins is as great as between the three P. knowlesi proteins themselves; the P. knowlesi beta-protein just 3' to this cysteine-rich region is homologous to the P. vivax protein but not to the other P. knowlesi proteins. Conservation of amino acid sequences among these organisms, separated in evolution, may indicate the regions where the adhesin function resides. C1 UNIV NOTRE DAME,DEPT BIOL SCI,NOTRE DAME,IN 46556. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. JOHNS HOPKINS UNIV,BALTIMORE,MD 21205. RP ADAMS, JH (reprint author), NIAID,MALARIA RES LAB,BETHESDA,MD 20892, USA. RI Adams, John/G-1800-2015 OI Adams, John/0000-0003-3707-7979 NR 31 TC 340 Z9 351 U1 2 U2 8 PU NATL ACAD PRESS 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 AUG 1 PY 1992 VL 89 IS 15 BP 7085 EP 7089 DI 10.1073/pnas.89.15.7085 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JF856 UT WOS:A1992JF85600088 PM 1496004 ER PT J AU CASSCELLS, W LAPPI, DA OLWIN, BB WAI, C SIEGMAN, M SPEIR, EH SASSE, J BAIRD, A AF CASSCELLS, W LAPPI, DA OLWIN, BB WAI, C SIEGMAN, M SPEIR, EH SASSE, J BAIRD, A TI ELIMINATION OF SMOOTH-MUSCLE CELLS IN EXPERIMENTAL RESTENOSIS - TARGETING OF FIBROBLAST GROWTH-FACTOR RECEPTORS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BASIC FGF; SAPORIN MITOTOXIN; EXPRESSION; BRAIN; FORMS; PROLIFERATION; PURIFICATION; MECHANISMS; CLONING; CHICK AB Factors in plasma and platelets do not fully account for the proliferation of smooth muscle cells in vascular injury, implying that additional factors are involved. Recently, we and others have observed that vascular injury regulates basic fibroblast growth factor, suggesting a further role for this pleiotropic factor. We report here that injury of rat arteries leads to an increase in fibroblast growth factor receptors in vascular smooth muscle cells. This up-regulation makes smooth muscle cells susceptible, in vitro and in vivo, to the lethal effects of a conjugate of basic fibroblast growth factor with the ribosome inactivator saporin. Saporin alone has no effect, whereas the conjugate kills proliferating, but not quiescent, smooth muscle cells in vitro. In vivo, one to three doses inhibit neointimal proliferation but have no apparent effect on the uninjured artery. Thus, the up-regulation of fibroblast growth factor receptors in vascular injury suggests new therapeutic possibilities for such refractory conditions as restenosis following balloon angioplasty. C1 UNIV WISCONSIN,DEPT BIOCHEM,MADISON,WI 53706. NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. SHRINERS HOSP CRIPPLED CHILDREN,IMMUNOL SECT,TAMPA,FL 33612. RP CASSCELLS, W (reprint author), WHITTIER INST DIABET & ENDOCRINOL,DEPT MOLEC & CELLULAR GROWTH BIOL,9894 GENESEE AVE,LA JOLLA,CA 92037, USA. FU NIDDK NIH HHS [DK-18811] NR 37 TC 133 Z9 134 U1 0 U2 2 PU NATL ACAD PRESS 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 AUG 1 PY 1992 VL 89 IS 15 BP 7159 EP 7163 DI 10.1073/pnas.89.15.7159 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JF856 UT WOS:A1992JF85600103 PM 1323129 ER PT J AU WALSH, CE LIU, JM XIAO, X YOUNG, NS NIENHUIS, AW SAMULSKI, RJ AF WALSH, CE LIU, JM XIAO, X YOUNG, NS NIENHUIS, AW SAMULSKI, RJ TI REGULATED HIGH-LEVEL EXPRESSION OF A HUMAN GAMMA-GLOBIN GENE INTRODUCED INTO ERYTHROID-CELLS BY AN ADENOASSOCIATED VIRUS VECTOR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PARVOVIRUS; HEMOGLOBINOPATHY; TRANSFECTION; HYPERSENSITIVE SITE ID DOMINANT CONTROL REGION; HEMATOPOIETIC STEM-CELLS; ADENOASSOCIATED VIRUS; INTEGRATION; LOCUS; DNA; AAV; REPLICATION; ENHANCER; CULTURE AB Gene therapy of severe hemoglobinopathies will require high-level expression of a transferred globin gene in erythroid cells. Distant regulatory elements flanking the beta-globin gene cluster, the locus control region, are needed for appropriate expression. We have explored the use of a human parvovirus, the adeno-associated virus (AAV), for globin gene transfer. The human (A)gamma-globin gene, linked to hypersensitivity site 2 from the locus control region of the beta-globin gene cluster, was subcloned into a plasmid (psub201) containing the AAV inverted terminal repeats. This construct was cotransfected with a helper plasmid containing trans-acting AAV genes into human 293 cells that had been infected with adenovirus. The recombinant AAV vector containing hypersensitivity site 2 stably introduced on average one or two unrearranged proviral copies into human K562 erythroleukemia cells. The transferred globin gene exhibited normal regulation upon hemin induction of erythroid maturation and was expressed at a level equivalent to a native chromosomal (A)gamma-globin gene. C1 NHLBI,CLIN HEMATOL BRANCH,BLDG 10,ROOM 7C103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. UNIV PITTSBURGH,DEPT BIOL SCI,PITTSBURGH,PA 15260. FU NIAID NIH HHS [5R29 AI25530]; NIDDK NIH HHS [5R01 DK 42701] NR 43 TC 146 Z9 149 U1 0 U2 1 PU NATL ACAD PRESS 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 AUG 1 PY 1992 VL 89 IS 15 BP 7257 EP 7261 DI 10.1073/pnas.89.15.7257 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JF856 UT WOS:A1992JF85600123 PM 1323131 ER PT J AU YANG, XJ RUVINOV, SB MILES, EW AF YANG, XJ RUVINOV, SB MILES, EW TI OVEREXPRESSION AND PURIFICATION OF THE SEPARATE TRYPTOPHAN SYNTHASE ALPHA AND BETA SUBUNITS FROM SALMONELLA-TYPHIMURIUM SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID SITE-DIRECTED MUTAGENESIS; ESCHERICHIA-COLI; ALPHA-2-BETA-2-COMPLEX; IDENTIFICATION; POSITION-49; CLEAVAGE C1 NIDDKO,BIOCHEM PHARMACOL LAB,BLDG 8,ROOM 225,BETHESDA,MD 20892. NR 32 TC 25 Z9 25 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 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD AUG PY 1992 VL 3 IS 4 BP 347 EP 354 DI 10.1016/1046-5928(92)90011-K PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA JH102 UT WOS:A1992JH10200011 PM 1422228 ER PT J AU KOLBANOVSKAYA, EY SATHYANARAYANA, BK WLODAWER, A KARPEISKY, MY AF KOLBANOVSKAYA, EY SATHYANARAYANA, BK WLODAWER, A KARPEISKY, MY TI INTRAMOLECULAR INTERACTIONS IN PANCREATIC RIBONUCLEASES SO PROTEIN SCIENCE LA English DT Article DE HYDROPHOBIC NUCLEI; NONPOLAR CONTACTS; RIBONUCLEASE-A ID AMINO-ACID-SEQUENCE; PROTEIN STRUCTURES; FOLDING PATHWAY; ACTIVE-SITE; ACCESSIBILITY; HOMOLOGY; PACKING; RNASE; RECOGNITION; RESOLUTION AB A detailed analysis of the composition and properties of hydrophobic nuclei and microclusters in pancreatic ribonuclease A (RNase A) has been carried out. Distance calculations for all noncovalently bonded atoms revealed that the average number of nonpolar contacts between a side chain of an amino acid and its neighbors is substantially larger if it involves hydrophobic residues rather than nonhydrophobic ones. However, the difference decreased when the number of contacts per nonpolar group and/or atom were calculated. Three main nuclei and five microclusters were identified, and their quantitative parameters were calculated. These nuclei include hydrophobic residues with a substantial number of nonpolar contacts with the environment (Phe 8, Phe 120, Phe 46, Tyr 25, Tyr 97, Ile 107, Leu 35, Ile 81, Val 54, Val 108, Met 29, Met 30). Hydrophobic nuclei of RNase A differ in shape and in composition, in the number of intranuclear contacts and of associated residues, as well as in their internal mobility. All eight cysteine residues are involved in nonpolar interactions with amino acid residues of hydrophobic nuclei. Active site amino acid residues of RNase A form a noncovalent contact network comprised of themselves, as well as of many conserved residues from hydrophobic nuclei. Sequence alignment with some other members of the RNase A family of proteins shows remarkable similarity in positions and in conservation of the main nonpolar residues, comprising cores of two (out of three) hydrophobic nuclei. A correlation was shown to exist between the average density of contacts for side-chain atoms and the number of amino acids to be found in the appropriate positions in the sequences of related mammalian ribonucleases. However, there are certain amino acid positions in the third, smaller nucleus, which are highly variable within the family. Taking into account that this nucleus is composed of residues belonging to different elements of the secondary structure, it is likely that the mutual orientation of these elements can be somehow different for these proteins. C1 VA ENGELHARDT MOLEC BIOL INST,VAVILOVA STR 32,MOSCOW,USSR. NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,MACROMOLEC STRUCT LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 40 TC 8 Z9 8 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD AUG PY 1992 VL 1 IS 8 BP 1050 EP 1060 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JM678 UT WOS:A1992JM67800010 PM 1304382 ER PT J AU THANKI, N RAO, JKM FOUNDLING, SI HOWE, WJ MOON, JB HUI, JO TOMASSELLI, AG HEINRIKSON, RL THAISRIVONGS, S WLODAWER, A AF THANKI, N RAO, JKM FOUNDLING, SI HOWE, WJ MOON, JB HUI, JO TOMASSELLI, AG HEINRIKSON, RL THAISRIVONGS, S WLODAWER, A TI CRYSTAL-STRUCTURE OF A COMPLEX OF HIV-1 PROTEASE WITH A DIHYDROXYETHYLENE-CONTAINING INHIBITOR - COMPARISONS WITH MOLECULAR MODELING SO PROTEIN SCIENCE LA English DT Article DE HUMAN IMMUNODEFICIENCY VIRUS; INHIBITOR; MOLECULAR MODELING; PROTEASE ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEINASE-INHIBITORS; REFINEMENT; RESOLUTION; BINDING; DESIGN; ISOSTERE AB The structure of a crystal complex of recombinant human immunodeficiency virus type 1 (HIV-1) protease with a peptide-mimetic inhibitor containing a dihydroxyethylene isostere insert replacing the scissile bond has been determined. The inhibitor is Noa-His-Hch-PSI-[CH(OH)CH(OH)]Vam-Ile-Amp (U-75875), and its K(i) for inhibition of the HIV-1 protease is < 1.0 nM (Noa = 1-naphthoxyacetyl, Hch = a hydroxy-modified form of cyclohexylalanine, Vam = a hydroxy-modified form of valine, Amp = 2-pyridylmethylamine). The structure of the complex has been refined to a crystallographic R factor of 0. 169 at 2.0 angstrom resolution by using restrained least-squares procedures. Root mean square deviations from ideality are 0.02 angstrom and 2.4-degrees, for bond lengths and angles, respectively. The bound inhibitor diastereomer has the R configurations at both of the hydroxyl chiral carbon atoms. One of the diol hydroxyl groups is positioned such that it forms hydrogen bonds with both the active site aspartates, whereas the other interacts with only one of them. Comparison of this X-ray structure with a model-built structure of the inhibitor, published earlier, reveals similar positioning of the backbone atoms and of the side-chain atoms in the P2-P2' region, where the interaction with the protein is strongest. However, the X-ray structure and the model differ considerably in the location of the P3 and P3' end groups, and also in the positioning of the second of the two central hydroxyl groups. Reconstruction of the central portion of the model revealed the source of the hydroxyl discrepancy, which, when corrected, provided a P1-P1' geometry very close to that seen in the X-ray structure. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,MACROMOLEC STRUCT LAB,FREDERICK,MD 21702. UPJOHN CO,UPJOHN LABS,KALAMAZOO,MI 49001. FU NCI NIH HHS [N01-CO-74101] NR 30 TC 76 Z9 78 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD AUG PY 1992 VL 1 IS 8 BP 1061 EP 1072 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JM678 UT WOS:A1992JM67800011 PM 1304383 ER PT J AU DARKO, DF IRWIN, MR RISCH, SC GILLIN, JC AF DARKO, DF IRWIN, MR RISCH, SC GILLIN, JC TI PLASMA BETA-ENDORPHIN AND NATURAL-KILLER-CELL ACTIVITY IN MAJOR DEPRESSION - A PRELIMINARY-STUDY SO PSYCHIATRY RESEARCH LA English DT Article DE AFFECTIVE DISORDER; OPIATE PEPTIDES; CELLULAR IMMUNITY ID CORTICOTROPIN-RELEASING-FACTOR; HYPOTHALAMIC-PITUITARY AXIS; LYMPHOCYTE-PROLIFERATION; AFFECTIVE-DISORDERS; CYTO-TOXICITY; NK CELL; IMMUNE; STRESS; SCHIZOPHRENIA; DEXAMETHASONE AB Low concentrations of beta-endorphin have been found to enhance human natural killer (NK) cell activity in vitro. Both beta-endorphin and NK activity are changed by clinical depression. To evaluate whether circulating concentrations of beta-endorphin have a role in the in vivo modulation of cellular immunity in humans, we measured plasma beta-endorphin and NK cell activity in 14 depressed patients and 14 age-matched control subjects. In the depressed patients, both plasma beta-endorphin and NK cell activity were reduced to 76% and 57%, respectively, of the mean levels in the control subjects. In addition, beta-endorphin showed a significant positive correlation with lytic units of NK cell activity in the combined group of all subjects and in the patient group (p = 0.04). but not in the control group. The study supports the hypothesis that circulating endorphin is correlated with NK cell activity in vivo. This correlation may be higher in the depressed patient group. C1 UNIV CALIF SAN DIEGO,SCH MED,DEPT PSYCHIAT,LA JOLLA,CA 92093. US DEPT VET AFFAIRS MED CTR,ALCOHOL RES CTR,SAN DIEGO,CA. EMORY UNIV,SCH MED,DEPT PSYCHIAT,ATLANTA,GA 30322. UNIV CALIF SAN DIEGO,NIMH,MENTAL HLTH CLIN RES CTR,LA JOLLA,CA 92093. RP DARKO, DF (reprint author), US DEPT VET AFFAIRS MED CTR,MENTAL HLTH RES CLIN,3350 LA JOLLA VILLAGE DR,SAN DIEGO,CA 92161, USA. RI Irwin, Michael/H-4870-2013 OI Irwin, Michael/0000-0002-1502-8431 FU NIMH NIH HHS [MH-30914, MH-42762, MH-44275] NR 35 TC 23 Z9 23 U1 2 U2 2 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 AUG PY 1992 VL 43 IS 2 BP 111 EP 119 DI 10.1016/0165-1781(92)90125-M PG 9 WC Psychiatry SC Psychiatry GA JR078 UT WOS:A1992JR07800001 PM 1410068 ER PT J AU EGAN, MF ELMALLAKH, RS SUDDATH, RL LOHR, JB BRACHA, HS WYATT, RJ AF EGAN, MF ELMALLAKH, RS SUDDATH, RL LOHR, JB BRACHA, HS WYATT, RJ TI CEREBROSPINAL-FLUID AND SERUM LEVELS OF NEURON-SPECIFIC ENOLASE IN PATIENTS WITH SCHIZOPHRENIA SO PSYCHIATRY RESEARCH LA English DT Article DE NEURODEGENERATION; NEURODEVELOPMENT; GLYCOLYTIC ENZYME ID DISEASE; NEUROLEPTICS AB Some patients with schizophrenia appear to have brain abnormalities, including enlarged third and lateral ventricles and reduced volumes of temporal lobe structures, These abnormalities could be attributed to a developmental abnormality or a neurodegenerative process. Neuron-specific enolase (NSE), a protein that is found primarily in neurons and neuroendocrine cells, has been used as an index of neuronal damage or degeneration. Levels of NSE in cerebrospinal fluid (CSF) and serum from 50 patients with acute and chronic schizophrenia were compared with those in normal and neurological control subjects. A double-antibody, solid phase iodinated radioimmunoassay was used to determine NSE levels. There was no evidence of elevated levels in patients with schizophrenia, whereas control subjects with neurological illnesses had increased levels of NSE in CSF. Because NSE is rapidly cleared from CSF, however, elevated levels could have been missed. Unmedicated patients tended to have lower levels than medicated patients. RP EGAN, MF (reprint author), ST ELIZABETH HOSP,NIMH,HOSP NEUROPSYCHIAT RES,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032, USA. NR 30 TC 11 Z9 14 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 AUG PY 1992 VL 43 IS 2 BP 187 EP 195 DI 10.1016/0165-1781(92)90133-N PG 9 WC Psychiatry SC Psychiatry GA JR078 UT WOS:A1992JR07800009 PM 1357702 ER PT J AU NEWMAN, F STEIN, MB TRETTAU, JR COPPOLA, R UHDE, TW AF NEWMAN, F STEIN, MB TRETTAU, JR COPPOLA, R UHDE, TW TI QUANTITATIVE ELECTROENCEPHALOGRAPHIC EFFECTS OF CAFFEINE IN PANIC DISORDER SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE COMPUTERIZED ELECTROENCEPHALOGRAPHY; ANXIETY; ALPHA-ACTIVITY; BETA-ACTIVITY; THETA-ACTIVITY ID EEG; ANXIETY; SEIZURES; ATTACKS AB It has been demonstrated that patients with panic disorder are more sensitive than normal control subjects to the anxiogenic effects of caffeine. The underlying physiologic basis for this difference is unclear. We examined the electroencephalographic (EEG) activity of seven patients with panic disorder and seven normal control subjects during the randomized double-blind, placebo-controlled administration of oral caffeine (7 mg/kg). EEG data were collected on-line from 28 electrodes; artifact-free epochs were selected manually for off-line Fourier transformation. Caffeine was associated with a significant increase in peak occipital alpha frequency and significant decreases in occipital alpha amplitude, central beta amplitude, and central theta amplitude. Despite the observation that caffeine increased anxiety more in the patients with panic disorder than in the normal control subjects, the two groups did not differ in their EEG responses to caffeine. C1 NIMH,ST ELIZABETHS HOSP,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NIMH,BIOL PSYCHIAT BRANCH,ANXIETY & AFFECT DISORDERS SECT,BETHESDA,MD 20892. NR 19 TC 19 Z9 19 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD AUG PY 1992 VL 45 IS 2 BP 105 EP 113 DI 10.1016/0925-4927(92)90004-N PG 9 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA KA574 UT WOS:A1992KA57400004 PM 1488468 ER PT J AU HILAKIVICLARKE, L LISTER, RG AF HILAKIVICLARKE, L LISTER, RG TI SOCIAL-STATUS AND VOLUNTARY ALCOHOL-CONSUMPTION IN MICE - INTERACTION WITH STRESS SO PSYCHOPHARMACOLOGY LA English DT Article DE AGGRESSION; STRESS; SOCIAL STATUS; ALCOHOL; MICE ID BEHAVIORAL DESPAIR; ETHANOL; RATS; ANXIETY; BRAIN; TESTS AB Dominant rats are found to consume less alcohol than their subordinate cage-mates. It is unclear whether the difference is due to dominant, aggressive animals consuming low levels of alcohol or whether social stress increases alcohol intake in subordinate animals. The present study investigated alcohol drinking patterns in aggressive alpha mice, their fight-stressed submissive cage-mates and non-fighting control mice before and after the establishment of social hierarchies. The results revealed that both moderately and severely fight-stressed submissive mice showed increased consumption of 5 % alcohol, expressed as g/kg, but only severely wounded submissive mice showed increased alcohol preference over total fluid consumption, as compared with alpha mice. The difference in alcohol consumption was not seen prior to the establishment of submissive and alpha status, indicating that the submissive mice increased their alcohol consumption only after experiencing fight-stress. The amount of alcohol consumed did not differ between alpha and non-fighting control mice. To further investigate the possible connection between alcohol intake and aggressivity, the mice were studied in the resident-intruder test before group-housing. The results failed to show a consistent pattern of correlations between the time spent in aggression in this test and subsequent alcohol intake measures. The data indicate that severe fight-stress increases alcohol consumption in mice. Alcohol intake of aggressive, dominant alpha mice is not significantly altered, as compared with non-fighting animals. Furthermore, the level of aggressiveness prior to the establishment of social status does not directly affect alcohol consumption. These results suggest that aggression and dominance are not critical in determining alcohol intake patterns, whereas being a target of severe social and physical stress significantly elevates alcohol consumption in mice. RP HILAKIVICLARKE, L (reprint author), NIAAA,CLIN STUDIES LAB,BLDG 10,ROOM 3C102,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 20 TC 22 Z9 22 U1 0 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD AUG PY 1992 VL 108 IS 3 BP 276 EP 282 DI 10.1007/BF02245112 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA JH254 UT WOS:A1992JH25400006 PM 1523279 ER PT J AU HILL, SC DAMASKA, BM LING, A PATTERSON, K DIBISCEGLIE, AM BRADY, RO BARTON, NW AF HILL, SC DAMASKA, BM LING, A PATTERSON, K DIBISCEGLIE, AM BRADY, RO BARTON, NW TI GAUCHER DISEASE - ABDOMINAL MR IMAGING FINDINGS IN 46 PATIENTS SO RADIOLOGY LA English DT Article DE GAUCHER DISEASE; LIVER, DISEASES; LIVER, MR; SPLEEN, DISEASES; SPLEEN, MR ID APPEARANCE; SPLEEN; LIVER; CT AB Abdominal magnetic resonance imaging findings were reviewed in 46 patients with Gaucher disease. All patients had hepatosplenomegaly at the time of initial imaging. Splenic nodules were present in 14 patients (30%) and varied in signal intensity. These nodules were isointense on T1-weighted and hypointense on T2-weighted images. Splenic infarcts were seen in 15 patients (33%), and four of these patients (9%) also had subcapsular fluid collections. Both nodules and infracts were present in the spleen in four patients (9%). Pathologic correlation was performed with specimens from two patients who underwent partial splenectomy. Focal areas of abnormal signal intensity were noted in the liver in nine patients (20%). They were either stellate or segmental, and may represent fibrotic septa with ischemic changes associated with aggregates of Gaucher cells. No changes were noted in the kidneys or abdominal lymph nodes. C1 NIDDKD,CTR CLIN,LIVER DIS SECT,BETHESDA,MD 20892. NINCDS,CTR CLIN,DEV & METABOL NEUROL BRANCH,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT RADIOL,WASHINGTON,DC 20007. CHILDRENS HOSP,NATL MED CTR,DEPT PATHOL,WASHINGTON,DC 20010. RP HILL, SC (reprint author), NIDDKD,CTR CLIN,DEPT DIAGNOST RADIOL,BLDG 10,RM 1C-660,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 11 TC 45 Z9 46 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 1992 VL 184 IS 2 BP 561 EP 566 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JE075 UT WOS:A1992JE07500051 PM 1620865 ER PT J AU EHRENREICH, H LANGE, M NEAR, KA ANNESER, F SCHOELLER, LAC SCHMID, R WINKLER, PA KEHRL, JH SCHMIEDEK, P GOEBEL, FD AF EHRENREICH, H LANGE, M NEAR, KA ANNESER, F SCHOELLER, LAC SCHMID, R WINKLER, PA KEHRL, JH SCHMIEDEK, P GOEBEL, FD TI LONG-TERM MONITORING OF IMMUNOREACTIVE ENDOTHELIN-1 AND ENDOTHELIN-3 IN VENTRICULAR CEREBROSPINAL-FLUID, PLASMA, AND 24-H URINE OF PATIENTS WITH SUBARACHNOID HEMORRHAGE SO RESEARCH IN EXPERIMENTAL MEDICINE LA English DT Article ID HUMAN CEREBRAL-ARTERIES; ARGININE-VASOPRESSIN; VASOSPASM; CELLS; RATS; SECRETION; PEPTIDE; ULTRASOUND; PREVENTION; RECEPTORS AB Endothelins (ETs), peptides that were originally isolated from endothelial cells, have extremely potent and long-lasting vasoconstricting effects on cerebral vessels in vitro and in vivo. Observations that astrocytes produce these peptides and that their ET production can be stimulated, e.g. by thrombin, and potentiated via a self-enhancing autoregulatory mechanism may have shed new light upon the pathogenesis of cerebrovasospasm (CVS). ETs are present at low levels in normal human cerebrospinal fluid (CSF). Few and contradictory reports exist on ET levels in subarachnoid hemorrhage (SAH)-associated CVS. We monitored ventricular CSF, plasma, and 24-h urine levels of immunoreactive endothelin-1 (ET-1) and endothelin-3 (ET-3) in seven patients with SAH. who did (five) or did not (two) develop CVS in the course of their disease, as well as in two patients with different conditions (acoustic neuroma/postoperative meningitis; hydro-/hematocephalus) over 7-19 days. A distinct peak of both ET-1 and ET-3 in CSF of patients with SAH coincided with clinically documented signs of CVS and was absent in CSF of patients with SAH but no CVS. CSF levels of ET-1 and ET-3 displayed a striking parallelism in all subjects. Plasma ET-1 levels were essentially in the normal range. ET-3 was not detectable in plasma under our assay conditions. The excretion profiles of ET-1 and ET-3 in 24-h urine revealed again a predominantly parallel behavior of the two peptides. Interestingly, patients with high ET levels in CSF showed simultaneous peaks in urinary ET excretion, expressed as nanograms per gram of creatinine. Our findings support an association of ETs with the pathogenic events following SAH. The well-documented effects of these peptides on cerebral vessels suggest they are mediators rather than markers of disease. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. UNIV MUNICH,KLINIKUM GROSSHADERN,DEPT NEUROSURG,W-8000 MUNICH 70,GERMANY. UNIV MUNICH,MED POLIKLIN,W-8000 MUNICH 2,GERMANY. OI Kehrl, John/0000-0002-6526-159X NR 52 TC 104 Z9 104 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0300-9130 J9 RES EXP MED JI Res. Exp. Med. PD AUG PY 1992 VL 192 IS 4 BP 257 EP 268 DI 10.1007/BF02576282 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JH751 UT WOS:A1992JH75100005 PM 1410800 ER PT J AU DANIELS, TE FOX, PC AF DANIELS, TE FOX, PC TI SALIVARY AND ORAL COMPONENTS OF SJOGRENS-SYNDROME SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID EPSTEIN-BARR-VIRUS; POLYMERASE CHAIN-REACTION; GLAND BIOPSY SPECIMENS; HLA-DR EXPRESSION; INTERLEUKIN-2 RECEPTOR; MONOCLONAL-ANTIBODIES; LYMPHOCYTE SUBSETS; PAROTID-GLAND; CLASS-II; XEROSTOMIA C1 UNIV CALIF SAN FRANCISCO,SCH DENT,DIV ORAL PATHOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,SJORGRENS SYNDROME CLIN,SAN FRANCISCO,CA 94143. NIDR,CLIN INVEST & PATIENT CARE BRANCH,CLIN INVEST SECT,BETHESDA,MD 20892. NR 70 TC 125 Z9 131 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD AUG PY 1992 VL 18 IS 3 BP 571 EP 589 PG 19 WC Rheumatology SC Rheumatology GA LA278 UT WOS:A1992LA27800006 PM 1496162 ER PT J AU GUPTA, S SINGH, M AF GUPTA, S SINGH, M TI BEHAVIOR OF SOME TRANSFORMS OF CORRELATION-COEFFICIENT FROM A BIVARIATE NORMAL SAMPLE CONTAMINATED WITH BIVARIATE NORMAL OUTLIERS SO SANKHYA-THE INDIAN JOURNAL OF STATISTICS SERIES B LA English DT Article DE TRANSFORM OF CORRELATION COEFFICIENT; BIVARIATE NORMAL CONTAMINATED OUTLIERS AB Distributional behaviour of some commonly used transformations of correlation coefficient from bivariate normal sample when it is contaminated with outliers is studied. The outliers are assumed to come from a bivariate normal population also. Approximations to the bias and mean squared error of sample correlation coefficient and its five transformation are obtained. These approximations are seen to compare well with their simulated values for several sets of parameters. For sample size 50 and ten percent outliers, all the transformations are robust to a change in correlation by 0.1 or a scaled location difference of up to 0.2 or a change in scale ratio in the range 0.8 to 1.2. The transformations tend to be non-robust when the outlier part differs by some combination of orientation, scale and location. A large sample size with a proportional increase in the number of outliers or the addition of more outliers also makes the transformations non-robust. C1 NICHHD,BETHESDA,MD 20892. VIRGINIA POLYTECH INST & STATE UNIV,BLACKSBURG,VA 24061. NR 18 TC 0 Z9 0 U1 0 U2 1 PU INDIAN STATISTICAL INST PI CALCUTTA PA 204-1 BARRACKPORE TRUNK RD, CALCUTTA 700 035, INDIA SN 0581-5738 J9 SANKHYA SER B PD AUG PY 1992 VL 54 BP 184 EP 199 PN 2 PG 16 WC Statistics & Probability SC Mathematics GA LB913 UT WOS:A1992LB91300005 ER PT J AU GUPTA, S AF GUPTA, S TI EFFICIENCY BALANCE THROUGH BIB AND GD DESIGNS SO SANKHYA-THE INDIAN JOURNAL OF STATISTICS SERIES B LA English DT Article DE BALANCED INCOMPLETE BLOCK DESIGN; GROUP DIVISIBLE DESIGN; EFFICIENCY BALANCE; REINFORCEMENT ID BLOCK-DESIGNS; PATTERNS AB Efficiency balanced designs are obtained through some variations of the technique of reinforcement using balanced incomplete block and group divisible designs. The techniques of this paper provide designs with number of treatments greater than v + 1. C1 NICHHD,BETHESDA,MD 20892. NO ILLINOIS UNIV,DE KALB,IL 60115. NR 12 TC 1 Z9 1 U1 0 U2 0 PU INDIAN STATISTICAL INST PI CALCUTTA PA 204-1 BARRACKPORE TRUNK RD, CALCUTTA 700 035, INDIA SN 0581-5738 J9 SANKHYA SER B PD AUG PY 1992 VL 54 BP 220 EP 226 PN 2 PG 7 WC Statistics & Probability SC Mathematics GA LB913 UT WOS:A1992LB91300007 ER PT J AU BLAIR, A ZAHM, SH PEARCE, NE HEINEMAN, EF FRAUMENI, JF AF BLAIR, A ZAHM, SH PEARCE, NE HEINEMAN, EF FRAUMENI, JF TI CLUES TO CANCER ETIOLOGY FROM STUDIES OF FARMERS SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH LA English DT Review DE AGRICULTURE; IMMUNOLOGY; PESTICIDES; REVIEW ID SOFT-TISSUE SARCOMAS; NON-HODGKINS-LYMPHOMA; CASE-REFERENT; UNITED-STATES; TRANSPLANT RECIPIENTS; PHENOXYACETIC ACIDS; OCCUPATIONAL RISK; PHYSICAL-FITNESS; MULTIPLE-MYELOMA; GASTRIC CARDIA AB This article summarizes cancer risks among farmers to clarify the magnitude of the problem and to suggest directions for future research. Significant excesses occurred for Hodgkin's disease, multiple myeloma, leukemia, skin melanomas, and cancers of the lip, stomach, and prostate. Nonsignificant increases in risk were also noted for non-Hodgkin's lymphoma and cancers of connective tissue and brain. These excesses occurred against a background of substantial deficits among farmers for total mortality and mortality from many specific diseases. The tumors vary in frequency, histology, and prognosis and do not fall into any obvious grouping. Two commonalities may be important. Several of the tumors excessive among farmers appear to be rising in the general population and are excessive among patients with naturally occurring or medically induced immunodeficiencies. Therefore epidemiologic studies on specific exposures among farmers may help explain the rising trend of certain cancers in developed countries and provide clues to mechanisms of action for environmental carcinogens. C1 WELLINGTON SCH MED,WELLINGTON,NEW ZEALAND. RP BLAIR, A (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,ROOM 418,BETHESDA,MD 20892, USA. RI Zahm, Shelia/B-5025-2015 NR 80 TC 249 Z9 260 U1 2 U2 11 PU SCAND J WORK ENV HEALTH PI HELSINKI PA TOPELIUKSENKATU 41A, SF-00250 HELSINKI, FINLAND SN 0355-3140 J9 SCAND J WORK ENV HEA JI Scand. J. Work Environ. Health PD AUG PY 1992 VL 18 IS 4 BP 209 EP 215 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA JL692 UT WOS:A1992JL69200001 PM 1411362 ER PT J AU HARAF, DJ DEVINE, S IHDE, DC VOKES, EE AF HARAF, DJ DEVINE, S IHDE, DC VOKES, EE TI THE EVOLVING ROLE OF SYSTEMIC THERAPY IN CARCINOMA OF THE LUNG SO SEMINARS IN ONCOLOGY LA English DT Article ID CELL BRONCHOGENIC-CARCINOMA; THORACIC RADIATION-THERAPY; HIGH-DOSE RADIATION; PHASE-II TRIAL; TERM FOLLOW-UP; COMBINATION CHEMOTHERAPY; RANDOMIZED TRIAL; STAGE-III; ONCOLOGY-GROUP; BRONCHIAL-CARCINOMA C1 UNIV CHICAGO,DEPT MED,CHICAGO,IL 60637. NCI,DEPT HLTH & HUMAN SERV,BETHESDA,MD 20892. RP HARAF, DJ (reprint author), UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,HEMATOL ONCOL SECT,5841 S MARYLAND,CHICAGO,IL 60637, USA. NR 94 TC 19 Z9 19 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 1992 VL 19 IS 4 SU 11 BP 72 EP 87 PG 16 WC Oncology SC Oncology GA JK970 UT WOS:A1992JK97000011 PM 1324527 ER PT J AU ALDROUBI, A UNSER, M EDEN, M AF ALDROUBI, A UNSER, M EDEN, M TI CARDINAL SPLINE FILTERS - STABILITY AND CONVERGENCE TO THE IDEAL SINC INTERPOLATOR SO SIGNAL PROCESSING LA English DT Article DE SHANNON SAMPLING THEOREM; CARDINAL SPLINE FILTERS; SPLINE INTERPOLATION; BAND-LIMITED SIGNAL RECONSTRUCTION; CONVERGENCE RATES AB In this paper, we provide an interpretation of polynomial spline interpolation as a continuous filtering process. We prove that the frequency responses of the cardinal spline filters converge to the ideal lowpass filter in all L(p)-norms with 1 less-than-or-equal-to p < + infinity as the order of the spline tends to infinity. We provide estimate's for the resolution errors and the interpolation errors of the various filters. We also derive an upper bound for the error associated with the reconstruction of bandlimited signals using polynomial splines. RP ALDROUBI, A (reprint author), NIH,NATL CTR RES SOURCES,DEPT HLTH & HUMAN SERV,MATH & IMAGE PROC GRP,BETHESDA,MD 20892, USA. RI Unser, Michael/A-1550-2008; Aldroubi, Akram/J-7186-2012 NR 0 TC 89 Z9 90 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-1684 J9 SIGNAL PROCESS JI Signal Process. PD AUG PY 1992 VL 28 IS 2 BP 127 EP 138 DI 10.1016/0165-1684(92)90030-Z PG 12 WC Engineering, Electrical & Electronic SC Engineering GA JK647 UT WOS:A1992JK64700001 ER PT J AU LEBIHAN, D AF LEBIHAN, D TI NMR IMAGING OF DIFFUSION AND PERFUSION IN BRAIN ISCHEMIA SO STROKE LA English DT Meeting Abstract C1 NIH,CTR CLIN,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD AUG PY 1992 VL 23 IS 8 BP 1201 EP 1201 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA JG050 UT WOS:A1992JG05000053 ER PT J AU HALLETT, M AF HALLETT, M TI RECOVERY OF BRAIN-FUNCTION AFTER ACUTE STROKE SO STROKE LA English DT Meeting Abstract C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD AUG PY 1992 VL 23 IS 8 BP 1203 EP 1203 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA JG050 UT WOS:A1992JG05000058 ER PT J AU POGREBNIAK, HW MERINO, MJ HAHN, SM MITCHELL, JB PASS, HI AF POGREBNIAK, HW MERINO, MJ HAHN, SM MITCHELL, JB PASS, HI TI SPIN TRAP SALVAGE FROM ENDOTOXEMIA - THE ROLE OF CYTOKINE DOWN-REGULATION SO SURGERY LA English DT Article; Proceedings Paper CT 53RD ANNUAL MEETING OF THE SOC OF UNIV SURGEONS CY FEB 13-15, 1992 CL CINCINNATI, OH SP SOC UNIV SURGEONS ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; INDUCTION; CACHECTIN; INFUSION; ISCHEMIA; RELEASE; NITRONE; INJURY; SHOCK AB Background. The spin trap alpha-phenyl-N-tert-butyl-nitrone (PBN) affords protection from the lethality of septic (lipopolysaccharide) shock. We hypothesized that PBN may work through down-regulation of the sepsis-induced cytokine cascade. Methods. C3H/HEN mice received 30 mg/kg lipopolysaccharide 15 minutes after pretreatment with PBN or vehicle. Animals were monitored for differences in behavior, histopathologic studies, survival, and serum levels of tumor necrosis factor (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin-6 (IL-6) after lipopolysaccharide. Northern blot analyses of TNF, IFN-gamma, c-fos, and IL-6 transcripts were also performed. Results. Seventy-two-hour survival was significantly higher in the PBN-treated (59160) compared with the saline-treated animals (13/60; p2 < 0.005), and the PBN group exhibited a blunted endotoxemic response. TNF levels were significantly lower in the PBN-treated animals at 1 to 6 hours, whereas IFN-gamma levels were depressed at 8 hours. PBN down-regulated TNF transcription at 30 minutes, with maximum lowering of all cytokine transcripts at 6 hours. PBN depressed c-fos transcription within 15 minutes of lipopolysaccharide injection. Conclusions. Spin trap protection from endotoxemia may be related to interruption of the cytokine network, with profound effects on transcription and protein elaboration. Such compounds may prove useful in not only sepsis but also other cytokine-free radical-related pathophysiologic alterations. C1 NCI,SURG BRANCH,THORAC ONCOL SECT,BLDG 10,ROOM 2B07,BETHESDA,MD 20892. NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NR 25 TC 51 Z9 51 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 AUG PY 1992 VL 112 IS 2 BP 130 EP 139 PG 10 WC Surgery SC Surgery GA JG451 UT WOS:A1992JG45100002 PM 1641756 ER PT J AU ALEXANDER, HR DOHERTY, GM VENZON, DJ MERINO, MJ FRAKER, DL NORTON, JA AF ALEXANDER, HR DOHERTY, GM VENZON, DJ MERINO, MJ FRAKER, DL NORTON, JA TI RECOMBINANT INTERLEUKIN-1 RECEPTOR ANTAGONIST (IL-1RA) - EFFECTIVE THERAPY AGAINST GRAM-NEGATIVE SEPSIS IN RATS SO SURGERY LA English DT Article; Proceedings Paper CT 53RD ANNUAL MEETING OF THE SOC OF UNIV SURGEONS CY FEB 13-15, 1992 CL CINCINNATI, OH SP SOC UNIV SURGEONS ID TUMOR-NECROSIS-FACTOR; SEPTIC SHOCK; MONOCLONAL-ANTIBODY; FACTOR-ALPHA; ESCHERICHIA-COLI; CACHECTIN; LETHAL; BACTEREMIA; ENDOTOXIN; APPEARANCE AB Background. Morbidity and mortality from bacterial sepsis remain high despite aggressive diagnostic and therapeutic intervention. Interleukin-1 has been implicated as mediator of the lethal effects of endotoxemia or bacterial sepsis. The current experiments were designed to evaluate the therapeutic efficacy of a human recombinant interleukin-1 receptor antagonist (IL-1ra) against polymicrobial gram-negative septicemia in rats. Methods. Male rats underwent placement of indwelling carotid arterial and superior vena caval catheters followed by cecal ligation and puncture (CLP). After 3 hours rats received either IL-1ra (10 mg/kg intravenous bolus followed by 5 mg/kg/hr) or an equal volume of vehicle intravenously for 24 hours. Heart rate, respirations, mean arterial blood pressure, and temperature were recorded at frequent intervals, and survival was assessed for 30 hours after CLP. Results. There were no differences in vital signs between groups at baseline or before treatment, and all animals appeared ill with huddled posture, piloerection, and hyperventilation. Twenty-four hours after CLP, IL-1ra significantly ameliorated bradycardia (p = 0.01), hypothermia (p = 0.001), and hypotension (p = 0.05), and 30-hour survival was significantly improved (71% vs 20%, p < 0.05). Conclusions. IL-1ra lessens the acute hemodynamic, hypothermic, and mortal effects of gram-negative sepsis induced by CLP in rats. These data suggest that IL-1 receptor blockade may be an important new treatment strategy against overwhelming bacterial sepsis. C1 NCI,BIOSTAT & DATA MANAGEMENT BRANCH,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. RP ALEXANDER, HR (reprint author), NCI,SURG BRANCH,SURG METAB SECT,BLDG 10 ROOM 2B17,BETHESDA,MD 20892, USA. RI Venzon, David/B-3078-2008 NR 25 TC 89 Z9 89 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 AUG PY 1992 VL 112 IS 2 BP 188 EP 194 PG 7 WC Surgery SC Surgery GA JG451 UT WOS:A1992JG45100009 PM 1386478 ER PT J AU SUTHERLAND, CM CHMIEL, JS HENSON, DE CUNNINGHAM, MP PEACE, BB WINCHESTER, DP AF SUTHERLAND, CM CHMIEL, JS HENSON, DE CUNNINGHAM, MP PEACE, BB WINCHESTER, DP TI PATIENT CHARACTERISTICS, METHODS OF DIAGNOSIS AND TREATMENT OF MELANOMA IN THE UNITED-STATES SO SURGERY GYNECOLOGY & OBSTETRICS LA English DT Article ID CUTANEOUS MELANOMA AB The American College of Surgeons performed a patient care and evaluation study of melanoma for 1981 and 1987 to determine the presenting symptoms, methods of evaluation, clinical management and resulting outcome. Melanomas of the skin, eye, mucous membrane, metastases with unknown primary site and miscellaneous sites were included. Details concerning 5,004 patients from 681 hospitals in the study in 1981 and 6,900 patients from 844 hospitals in the study in 1987 were obtained-most melanomas were located in the skin; a decline in symptoms occurred at initial diagnosis, an increase in age at first diagnosis was reported, most melanomas were in Caucasian patients; slightly more melanomas occurred in men than women; more melanomas occurred in men on the head and neck and trunk, and more in the lower extremity in women; most tumors were not large in diameter; a significant shift was reported to lower levels of Clark's invasion, and a significant amount of unknowns existed in the Breslow's thickness of invasion. The large number of unknowns makes analysis difficult, but there seems to be some shift toward thinner levels of Breslow's in tumors in which it was known, from 1981 to 1987. Only a small proportion of patients in the current series was known to have node involvement or known distant metastases. An overall decline in diagnostic studies occurred between 1981 and 1987. C1 NORTHWESTERN UNIV,SCH MED,CTR CANC,BIOMETRY SECT,CHICAGO,IL 60611. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. ST FRANCIS HOSP,DEPT SURG,CHICAGO,IL. HCA COLISEUM MED CTR,MACON,IL. AMER COLL SURGEONS,CHICAGO,IL 60611. RP SUTHERLAND, CM (reprint author), TULANE UNIV,SCH MED,DEPT SURG,NEW ORLEANS,LA 70112, USA. NR 4 TC 13 Z9 13 U1 0 U2 0 PU FRANKLIN H MARTIN FOUNDATION PI CHICAGO PA 55 E ERIE ST, CHICAGO, IL 60611 SN 0039-6087 J9 SURG GYNECOL OBSTET JI Surg. Gynecol. Obstet. PD AUG PY 1992 VL 175 IS 2 BP 129 EP 134 PG 6 WC Obstetrics & Gynecology; Surgery SC Obstetrics & Gynecology; Surgery GA JG450 UT WOS:A1992JG45000008 PM 1636137 ER PT J AU CHIUEH, CC HUANG, SJ MURPHY, DL AF CHIUEH, CC HUANG, SJ MURPHY, DL TI ENHANCED HYDROXYL RADICAL GENERATION BY 2'-METHYL ANALOG OF MPTP - SUPPRESSION BY CLORGYLINE AND DEPRENYL SO SYNAPSE LA English DT Note DE HYDROXYL RADICAL; STRIATUM; MPTP; PARKINSONS DISEASE; CLORGYLINE; DEPRENYL; SODIUM SALICYLATE ID PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; LIPID-PEROXIDATION; IRON; MPP+; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; BIOACTIVATION; SALICYLATE; METABOLITE; ASSAY AB Sodium salicylate was infused through a microdialysis probe placed in the striatum of anesthetized rats in order to assay the formation of hydroxyl radical (. OH) in the extracellular fluid in vivo. In addition to causing sustained dopamine release, intrastriatal infusion of the 2'-methyl analog of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (2'CH3-MPTP) increased the formation of 2,3-dihydroxybenzoic acid (2,3-DHBA), the nonenzymatic . OH adduct of salicylate in the brain dialysate. Inhibition of monoamine oxidase (MAO) by clorgyline and deprenyl completely blocked the formation of 2,3-DHBA and the sustained dopamine overflow induced by 2'-CH3-MPTP. The results indicate that the enhanced formation of cytotoxic . OH by 2'-CH3-MPTP is suppressed by MAO inhibitors. These data support the hypothesis that the protective effect of MAO inhibitors on the neurotoxicity induced by MPTP analogues may be due not only to the inhibition of MPTP metabolism by MAO but also the blockade of the formation of . OH free radicals. An enhanced generation of cytotoxic . OH free radicals in the striatum which in turn leads to oxidant damage may be relevant to the development of parkinsonism-like changes in animals produced by MPTP analogues. RP CHIUEH, CC (reprint author), NIMH,CTR CLIN,CLIN SCI LAB,10-3D-41,BETHESDA,MD 20892, USA. NR 24 TC 74 Z9 74 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 AUG PY 1992 VL 11 IS 4 BP 346 EP 348 DI 10.1002/syn.890110410 PG 3 WC Neurosciences SC Neurosciences & Neurology GA JF141 UT WOS:A1992JF14100009 PM 1323883 ER PT J AU MURALIDHAR, S VOLL, MJ AF MURALIDHAR, S VOLL, MJ TI GENETIC-BASIS FOR VARIABILITY IN ARABINOSE FERMENTATION IN VIBRIO-PARAHAEMOLYTICUS SO SYSTEMATIC AND APPLIED MICROBIOLOGY LA English DT Article DE V-PARAHAEMOLYTICUS; ARABINOSE FERMENTATION; ARA GENES; VARIABLE CHARACTERISTIC; GENE CLONING; DNA DNA HYBRIDIZATION ID THERMOSTABLE DIRECT HEMOLYSIN; ESCHERICHIA-COLI; NUMERICAL TAXONOMY; BACILLUS-SUBTILIS; DNA; CLONING; SEQUENCES; STRAINS; CHOLERAE AB Ability to ferment arabinose is a variable characteristic in the species Vibrio parahaemolyticus. To study the genetic basis of this variability, the arabinose fermentation genes from an arabinose utilizing strain were cloned into the plasmid vector pBR322. Complementation studies employing plasmids deleted in segments of the cloned DNA established the presence of genes analogous to the araA, araB, araC, and araD genes of E. coli. The order of the ara genes in V. parahaemolyticus is different than that in Escherichia coli or Bacillus subtilis. Three radioactively labelled probes spanning the ara structural gene region were hybridized under stringent conditions with HindIII digested genomic DNA from arabinose positive and negative strains of V. parahaemolyticus and other Vibrio species. No DNA homologous to the probes was found in the arabinose negative V. parahaemolyticus strains indicating that absence rather than mutational inactivation of gene expression was responsible for the Ara- phenotype. Little or no hybridization of the ara probes to arabinose positive Vibrio fluvialis and Vibrio hollisae strains was detected. C1 UNIV MARYLAND,DEPT MICROBIOL,COLL PK,MD 20742. NIAID,VIRAL DIS LAB,ROCKVILLE,MD 20852. NR 29 TC 0 Z9 0 U1 0 U2 2 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0723-2020 J9 SYST APPL MICROBIOL JI Syst. Appl. Microbiol. PD AUG PY 1992 VL 15 IS 3 BP 420 EP 426 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA JM924 UT WOS:A1992JM92400014 ER PT J AU MARR, MC PRICE, CJ MYERS, CB MORRISSEY, RE AF MARR, MC PRICE, CJ MYERS, CB MORRISSEY, RE TI DEVELOPMENTAL STAGES OF THE CD(R) (SPRAGUE-DAWLEY) RAT SKELETON AFTER MATERNAL EXPOSURE TO ETHYLENE-GLYCOL SO TERATOLOGY LA English DT Article AB Ethylene glycol (EG), a chemical which causes skeletal malformations in rats, was administered by gavage to sperm positive CD(R) rats on gestational days (gd) 6 through 15 at doses of 0 or 2,500 mg/kg/day to assess its effects on the pre- and postnatal skeletal development. Dams and fetuses/pups were killed on gd 18, 20, postnatal day (pnd) 1, 4, 14, 21, or 63, and offspring were double-stained for examination of skeletal malformations and degree of ossification of rapidly developing skeletal districts. No difference in gestational day of delivery between controls and the EG-treated dams was seen. Fetal weights per litter were significantly decreased with EG treatment in both the gd 18 and 20 groups. Pup body weight on pnd 1 was significantly below controls; however, EG had no effect on pup body weight on pnd 4-63. The percentage of fetuses/pups with skeletal malformations per litter was significantly increased after EG exposure for all time points except at pnd 63, with a predominance of axial skeletal defects. The percentages of total ossification, of sternabrae ossified, and of vertabral centra ossified were significantly reduced in the EG groups on gd 20 and on pnd 1-21, but not on gd 18 or on pnd 63. When the ossification data were subjected to statistical analysis with fetal/pup weights as a covariate, the values for EG-exposed pups on gd 20 were not statistically significantly different from the control values. The reduced ossification values for EG-exposed pups on pnd 1-21 retained statistical significance even after covariate analysis. There was no effect of dose or body weight on ossification of fore- or hindlimb digits. In conclusion, the differences in incidence of skeletal alterations observed prenatally and through pnd 21 were not evident by pnd 63, suggesting that perinatal skeletal abnormalities may not always be permanent. C1 NIEHS,NATL TOXICOL PROGRAM,DEV & REPROD TOXICOL GRP,RES TRIANGLE PK,NC 27709. RP MARR, MC (reprint author), RES TRIANGLE INST,CTR LIFE SCI & TOXICOL,RES TRIANGLE PK,NC 27709, USA. FU NIEHS NIH HHS [N01-ES-55080] NR 12 TC 30 Z9 30 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 0040-3709 J9 TERATOLOGY JI Teratology PD AUG PY 1992 VL 46 IS 2 BP 169 EP 181 DI 10.1002/tera.1420460210 PG 13 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA JF754 UT WOS:A1992JF75400009 PM 1440420 ER PT J AU DALY, JW SECUNDA, SI GARRAFFO, HM SPANDE, TF WISNIESKI, A NISHIHIRA, C COVER, JF AF DALY, JW SECUNDA, SI GARRAFFO, HM SPANDE, TF WISNIESKI, A NISHIHIRA, C COVER, JF TI VARIABILITY IN ALKALOID PROFILES IN NEOTROPICAL POISON FROGS (DENDROBATIDAE) - GENETIC VERSUS ENVIRONMENTAL DETERMINANTS SO TOXICON LA English DT Article ID SKIN ALKALOIDS; MYOBATRACHIDAE; CLASSIFICATION AB Dendrobatid frogs produce a diverse set of alkaloids, whose profiles appear characteristic of frogs of each species or, in the case of variable species, of each population. In the case of one widespread species, Dendrobates auratus, alkaloid profiles in extracts of skin are markedly different in three populations, one from a Pacific island, Isla Taboga, Panama, one from central mountains in Panama, and the third from the Caribbean coast in Costa Rica. The first contains three major classes of dendrobatid alkaloids, the histrionicotoxins, the pumiliotoxin-A class and the decahydroquinolines. The second contains mainly histrionicotoxins, pumiliotoxin-A class alkaloids and one indolizidine. The third contains histrionicotoxins, a homopumiliotoxin, one decahydroquinoline, and a variety of indolizidines, quinolizidines and pyrrolizidines. Frogs from Isla Taboga or a nearby island were introduced into the Manoa Valley, Oahu, Hawaii, in 1932. Remarkably, although alkaloids of the pumiliotoxin-A class and one decahydroquinoline are still major constituents in skin extracts of Hawaiian frogs descended from the 1932 founding population, histrionicotoxins are absent and a novel tricyclic alkaloid is present. Offspring of wild-caught parents from Hawaii, Panama or Costa Rica raised in indoor terrariums on a diet of crickets and fruit flies do not contain detectable amounts of skin alkaloids. Offspring raised in large outside terrariums in Hawaii and fed mainly wild-caught termites and fruit flies do contain the same profile of alkaloids as their wild-caught parents in Hawaii, but at reduced levels. The genetic, environmental and dietary determinants of alkaloid profiles in dendrobatid frogs remain obscure, in particular the underlying cause for total absence in terrarium-reared frogs. C1 BALTIMORE ZOO,DEPT HERPETOL,BALTIMORE,MD 21217. NATL AQUARIUM,BALTIMORE,MD 21202. RP DALY, JW (reprint author), NIH,BIOORGAN CHEM LAB,BETHESDA,MD 20892, USA. NR 15 TC 48 Z9 51 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0041-0101 J9 TOXICON JI Toxicon PD AUG PY 1992 VL 30 IS 8 BP 887 EP 898 DI 10.1016/0041-0101(92)90387-K PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA JF908 UT WOS:A1992JF90800010 PM 1523680 ER PT J AU CONNOR, HD GAO, WS NUKINA, S LEMASTERS, JJ MASON, RP THURMAN, RG AF CONNOR, HD GAO, WS NUKINA, S LEMASTERS, JJ MASON, RP THURMAN, RG TI EVIDENCE THAT FREE-RADICALS ARE INVOLVED IN GRAFT FAILURE FOLLOWING ORTHOTOPIC LIVER-TRANSPLANTATION IN THE RAT - AN ELECTRON-PARAMAGNETIC RESONANCE SPIN TRAPPING STUDY SO TRANSPLANTATION LA English DT Article ID CAROLINA RINSE SOLUTION; COLD ISCHEMIC STORAGE; REPERFUSION INJURY; PRESERVATION; OXYGEN; MYOCARDIUM; CONTRIBUTE; NITRONE; KIDNEYS; INVIVO AB The purpose of these studies was to determine whether free radicals were formed as a consequence of reperfusion during orthotopic liver transplantation and whether their formation was related to graft failure. Grafts were stored for 18 hr in Euro-Collins solution or for 48 hr in University of Wisconsin solution (nonsurvival conditions) and reperfused with blood containing the spin trap alpha-phenyl N-tert-butylnitrone (PBN). Venous blood samples (4-5 ml) were collected, and serum was extracted with chloroform and methanol (2:1) and analyzed for radical adducts by electron paramagnetic resonance (EPR) spectroscopy. In samples from livers stored under nonsurvival conditions, EPR spectra were detected indicating the presence of PBN radical adducts. In contrast, radical adduct formation was 3- to 4-fold lower in similar experiments performed with untransplanted livers or with livers stored under survival conditions (1 hr in Ringer's solution or 24 hr in UW solution). Oxygen radicals are most likely involved in the production of radical adducts because formation was nearly completely prevented by superoxide dismutase plus catalase or Carolina rinse, which contains glutathione, desferrioxamine mesylate, and allopurinol. Radical adduct formation was much greater in a blood-free perfusion system where oxygen delivery was high, suggesting that blood elements are not necessary for radical adduct formation. An inverse correlation between survival of livers stored in UW solution and radical adduct signal was observed in this study. Thus, it is concluded that free radicals formed during reperfusion are involved in the mechanism of graft failure following liver transplantation in the rat. C1 UNIV N CAROLINA,DEPT PHARMACOL,HEPATOBIOL & TOXICOL LAB,CB 7365 FLOB,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT CELL BIOL & ANAT,CELL BIOL LABS,CHAPEL HILL,NC 27599. NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. FU NIAAA NIH HHS [AA-03624]; NIDDK NIH HHS [DK-37034] NR 27 TC 109 Z9 110 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 AUG PY 1992 VL 54 IS 2 BP 199 EP 204 DI 10.1097/00007890-199208000-00002 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA JJ753 UT WOS:A1992JJ75300002 PM 1323148 ER PT J AU LAYNE, SP MERGES, MJ DEMBO, M SPOUGE, JL CONLEY, SR MOORE, JP RAINA, JL RENZ, H GELDERBLOM, HR NARA, PL AF LAYNE, SP MERGES, MJ DEMBO, M SPOUGE, JL CONLEY, SR MOORE, JP RAINA, JL RENZ, H GELDERBLOM, HR NARA, PL TI FACTORS UNDERLYING SPONTANEOUS INACTIVATION AND SUSCEPTIBILITY TO NEUTRALIZATION OF HUMAN-IMMUNODEFICIENCY-VIRUS SO VIROLOGY LA English DT Article ID HTLV-III LAV; REVERSE-TRANSCRIPTASE; ENVELOPE GLYCOPROTEIN; OLIGOMERIC STRUCTURE; FINE-STRUCTURE; CELL-ADHESION; SOLUBLE CD4; TYPE-1; HIV-1; INFECTION C1 LOS ALAMOS NATL LAB,DIV THEORET,BIOL & BIOPHYS GRP,LOS ALAMOS,NM 87545. NCI,VIRUS BIOL SECT,TUMOR CELL BIOL LAB,FREDERICK,MD 21701. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. PROGRAM RESOURCES INC,FREDERICK,MD 21701. AARON DIAMOND AIDS RES CTR,NEW YORK,NY 10016. AMER BIOTECHNOL INC,CAMBRIDGE,MA 02139. FED HLTH OFF,ROBERT KOCH INST,W-1000 BERLIN 65,GERMANY. RI Dembo, Micah/C-2755-2013 NR 65 TC 285 Z9 286 U1 1 U2 5 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 AUG PY 1992 VL 189 IS 2 BP 695 EP 714 DI 10.1016/0042-6822(92)90593-E PG 20 WC Virology SC Virology GA JF684 UT WOS:A1992JF68400030 PM 1386485 ER PT J AU CHANG, DC HAYNES, JI BRADY, JN CONSIGLI, RA AF CHANG, DC HAYNES, JI BRADY, JN CONSIGLI, RA TI THE USE OF ADDITIVE AND SUBTRACTIVE APPROACHES TO EXAMINE THE NUCLEAR-LOCALIZATION SEQUENCE OF THE POLYOMAVIRUS MAJOR CAPSID PROTEIN-VP1 SO VIROLOGY LA English DT Note ID AMINO-ACID SEQUENCE; LARGE-T-ANTIGEN; TRANSPORT SIGNAL; LOCATION SIGNAL; STRUCTURAL PROTEINS; BINDING-PROTEINS; XENOPUS-LAEVIS; SV40; IDENTIFICATION; VP1 C1 KANSAS STATE UNIV AGR & APPL SCI,DIV BIOL,VIROL & ONCOL SECT,MANHATTAN,KS 66506. NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA09418, CA07319] NR 52 TC 41 Z9 43 U1 2 U2 5 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 AUG PY 1992 VL 189 IS 2 BP 821 EP 827 DI 10.1016/0042-6822(92)90615-V PG 7 WC Virology SC Virology GA JF684 UT WOS:A1992JF68400052 PM 1322607 ER PT J AU BILAN, PJ MITSUMOTO, Y MAHER, F SIMPSON, IA KLIP, A AF BILAN, PJ MITSUMOTO, Y MAHER, F SIMPSON, IA KLIP, A TI DETECTION OF THE GLUT3 FACILITATIVE GLUCOSE TRANSPORTER IN RAT L6 MUSCLE-CELLS - REGULATION BY CELLULAR-DIFFERENTIATION, INSULIN AND INSULIN-LIKE GROWTH FACTOR-I SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID SKELETAL-MUSCLE; EXPRESSION; RECRUITMENT; STIMULATION; PROTEIN; TISSUES; LIVER C1 HOSP SICK CHILDREN,DIV CELL BIOL,555 UNIV AVE,TORONTO M5G 1X8,ONTARIO,CANADA. NIDDK,DIABET BRANCH,EXPTL DIABET METAB & NUTR SECT,BETHESDA,MD 20892. NR 27 TC 61 Z9 62 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 JUL 31 PY 1992 VL 186 IS 2 BP 1129 EP 1137 DI 10.1016/0006-291X(92)90864-H PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JF844 UT WOS:A1992JF84400076 PM 1497646 ER PT J AU ZHANG, K PAPAGEORGE, AG LOWY, DR AF ZHANG, K PAPAGEORGE, AG LOWY, DR TI MECHANISTIC ASPECTS OF SIGNALING THROUGH RAS IN NIH-3T3 CELLS SO SCIENCE LA English DT Article ID GTPASE-ACTIVATING PROTEIN; SACCHAROMYCES-CEREVISIAE; TYROSINE PHOSPHORYLATION; NUCLEOTIDE BINDING; CYCLASE PATHWAY; GROWTH-FACTOR; KINASE-C; GENE; P21RAS; GAP AB Serum and growth factors can increase the proportion of Ras in the active guanosine triphosphate (GTP)-bound form. Growth factors might stimulate guanine nucleotide exchange or decrease the activity of the guanosine triphosphatase-activating proteins GAP and neurofibromin (NF1). In NIH 3T3 cells that overexpress the mutant Ras protein His116, which releases bound guanine nucleotide at a constitutively high rate and retains sensitivity to GAP and NF1, the proportion of GTP bound to the His116 protein was not altered by serum or platelet-derived growth factor. However, these mitogens increased the proportion of Ras in the GTP-bound form in cells that overexpressed control Ras proteins with a normal intrinsic rate of guanine nucleotide release. The amount of GTP-bound His116 or control Ras proteins was higher in cells at low density than in cells at high density, which have more GAP-like activity. The lower proportion of GTP-bound Ras in NIH 3T3 cells at high density may result from increased GAP-like activity. By contrast, serum and platelet-derived growth factors appear to stimulate guanine nucleotide exchange. RP ZHANG, K (reprint author), NCI,CELLULAR ONCOL LAB,BLDG 37,ROOM 1B-26,BETHESDA,MD 20892, USA. NR 34 TC 82 Z9 82 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 JUL 31 PY 1992 VL 257 IS 5070 BP 671 EP 674 DI 10.1126/science.1496380 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JF852 UT WOS:A1992JF85200037 PM 1496380 ER PT J AU MANNS, A WILKS, RJ MURPHY, EL HAYNES, G FIGUEROA, JP BARNETT, M HANCHARD, B BLATTNER, WA AF MANNS, A WILKS, RJ MURPHY, EL HAYNES, G FIGUEROA, JP BARNETT, M HANCHARD, B BLATTNER, WA TI A PROSPECTIVE-STUDY OF TRANSMISSION BY TRANSFUSION OF HTLV-I AND RISK-FACTORS ASSOCIATED WITH SEROCONVERSION SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID VIRUS TYPE-I; CELL LEUKEMIA-VIRUS; BLOOD-TRANSFUSION; INFECTION; DONORS; SEROPREVALENCE; MYELOPATHY; RECIPIENTS; DISEASE AB To evaluate the risk of transfusion-related transmission of HTLV-I in Jamaica, a prospective study was initiated, prior to availability of a licensed HTLV-I serological screening assay. This information would prove useful in formulating strategies for blood-donor screening. We followed 118 pre-transfusion HTLV-I-negative transfusion recipients at monthly intervals posttransfusion for 1 year. Laboratory and questionnaire data were obtained at each visit to evaluate the clinical and immunological status of recipients. Cumulative incidence of HTLV-I seroconversion was estimated and risk-factor data associated with seroconversion among 66 HTLV-I-exposed transfusion recipients were analyzed. Seroconversion occurred in 24/54 (44%) of recipients of HTLV-I-positive cellular blood components, 0/12 recipients of positive non-cellular donor units and 0/52 recipients of HTLV-I-negative donor units. Significant risk factors associated with recipient seroconversion were receipt of a seropositive cellular blood component stored for less than one week [odds ratio (OR) = 6.34,95% confidence interval (Cl) = 1.83 to 21.92], male sex (OR = 4.79, 95% Cl = 1.15 to 20.0) or use of immunosuppressive therapy at time of transfusion (OR = 12.20, 95% Cl = 0.95 to 156). Risk of blood-borne infection per person per year in Jamaica was estimated to be 0.009%. Our results confirm that blood transfusion carries a significant risk of HTLV-I transmission and that screening of donor blood effectively prevents HTLV-I seroconversion. Recipients at greatest risk for seroconversion were those who required multiple transfusions or who were receiving immunosuppressive therapy at the time of transfusion. These patients should be given priority in receiving selectively screened blood components, if universal blood-donor screening for HTLV-I is not possible. C1 UNIV W INDIES,DEPT PATHOL,KINGSTON 7,JAMAICA. UNIV W INDIES,TROP MED RES UNIT,KINGSTON 7,JAMAICA. UNIV CALIF SAN FRANCISCO,DEPT LAB MED,SAN FRANCISCO,CA 94143. NATL TRANSFUS SERV,KINGSTON,JAMAICA. MINIST HLTH,KINGSTON,JAMAICA. RES TRIANGLE INST,WASHINGTON,DC 20036. RP MANNS, A (reprint author), NCI,VIRAL EPIDEMIOL SECT,BETHESDA,MD 20892, USA. NR 26 TC 140 Z9 143 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 30 PY 1992 VL 51 IS 6 BP 886 EP 891 DI 10.1002/ijc.2910510609 PG 6 WC Oncology SC Oncology GA JG020 UT WOS:A1992JG02000008 PM 1639536 ER PT J AU ADAMI, HO HSING, AW MCLAUGHLIN, JK TRICHOPOULOS, D HACKER, D EKBOM, A PERSSON, I AF ADAMI, HO HSING, AW MCLAUGHLIN, JK TRICHOPOULOS, D HACKER, D EKBOM, A PERSSON, I TI ALCOHOLISM AND LIVER-CIRRHOSIS IN THE ETIOLOGY OF PRIMARY LIVER-CANCER SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID HEPATOCELLULAR-CARCINOMA; CIGARETTE-SMOKING; HEPATITIS-B; CONSUMPTION; RISK; MORTALITY; TOBACCO; SWEDEN AB The aim of this study was to determine the risk of developing primary liver cancer in patients with a diagnosis of alcoholism, liver cirrhosis, or both. Three population-based, mutually exclusive cohorts were defined on the basis of hospital discharge diagnoses between 1965 and 1983. Complete follow-up through 1984-excluding the first year of follow-up-showed that among 8,517 patients with a diagnosis of alcoholism, 13 cancers occurred, vs. 4.2 expected (standardized incidence ratio (SIR) = 3.1; 95% confidence interval (Cl) = 1.6 to 5.3); among 3,589 patients with liver cirrhosis, 59 cancers occurred, vs. 1.7 expected (SIR = 35.1; 95% Cl = 26.7 to 45.3), and among 836 patients with both diagnoses, 11 cancers occurred, vs. 0.3 expected (SIR = 34.3; 95% Cl = 17.1 to 61.3). Thus, alcoholism alone entailed a moderately increased risk and alcoholism with liver cirrhosis did not increase the high relative risk for liver cancer more than cirrhosis alone. We conclude that alcohol intake may be a liver carcinogen only by being causally involved in the development of cirrhosis; and further, that the risk of developing liver cancer following cirrhosis in this population is similar to or higher than that after chronic hepatitis-B-virus infection in other Western countries. C1 NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. UNIV HOSP UPPSALA,DEPT OBSTET & GYNAECOL,UPPSALA,SWEDEN. RP ADAMI, HO (reprint author), UNIV HOSP UPPSALA,CANC EPIDEMIOL UNIT,S-75185 UPPSALA,SWEDEN. RI Hacker, David/D-5134-2011; OI Hacker, David/0000-0002-0762-9667 NR 26 TC 81 Z9 82 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 JUL 30 PY 1992 VL 51 IS 6 BP 898 EP 902 DI 10.1002/ijc.2910510611 PG 5 WC Oncology SC Oncology GA JG020 UT WOS:A1992JG02000010 PM 1639537 ER PT J AU KYRIAKIS, JM APP, H ZHANG, XF BANERJEE, P BRAUTIGAN, DL RAPP, UR AVRUCH, J AF KYRIAKIS, JM APP, H ZHANG, XF BANERJEE, P BRAUTIGAN, DL RAPP, UR AVRUCH, J TI RAF-1 ACTIVATES MAP KINASE-KINASE SO NATURE LA English DT Article ID THREONINE PROTEIN-KINASE; EPIDERMAL GROWTH-FACTOR; T-CELL ACTIVATION; TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; INSULIN; PATHWAYS; CASCADE AB THE normal cellular homologue of the acutely transforming oncogene v-raf is c-raf-1, which encodes a serine/threonine protein kinase that is activated by many extracellular stimuli1. The physiological substrates of the protein c-Raf-1 are unknown. The mitogen-activated protein (MAP) kinases Erk1 and 2 are also activated by mitogens through phosphorylation of Erk tyrosine and threonine residues catalysed by a protein kinase of relative molecular mass 50,000, MAP kinase-kinase (MAPK-K)2-7. Here we report that MAPK-K as well as Erk1 and 2 are constitutively active in v-raf-transformed cells. MAPK-K partially purified from v-raf-transformed cells or from mitogen-treated cells3 can be deactivated by phosphatase 2A. c-Raf-1 purified after mitogen stimulation can reactivate the phosphatase 2A-inactivated MAPK-K over 30-fold in vitro. c-Raf-1 reactivation of MAPK-K coincides with the selective phosphorylation at serine/threonine residues of a polypeptide with M(r) 50,000 which coelutes precisely on cation-exchange chromatography with the MAPK-K activatable by c-Raf-1. These results indicate that c-Raf-1 is an immediate upstream activator of MAPK-K in vivo. To our knowledge, MAPK-K is the first physiological substrate of the c-raf-1 protooncogene product to be identified. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. BROWN UNIV,DIV BIOL & MED,PROVIDENCE,RI 02912. RP KYRIAKIS, JM (reprint author), MASSACHUSETTS GEN HOSP,MED SERV,DIABET UNIT,149 13TH ST,BOSTON,MA 02129, USA. NR 26 TC 1122 Z9 1131 U1 2 U2 30 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUL 30 PY 1992 VL 358 IS 6385 BP 417 EP 421 DI 10.1038/358417a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JF853 UT WOS:A1992JF85300057 PM 1322500 ER PT J AU GRZESIEK, S BAX, A AF GRZESIEK, S BAX, A TI CORRELATING BACKBONE AMIDE AND SIDE-CHAIN RESONANCES IN LARGER PROTEINS BY MULTIPLE RELAYED TRIPLE RESONANCE NMR SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID MAGNETIZATION TRANSFER; SPECTROSCOPY; GAMMA AB A new three-dimensional triple resonance NMR experiment is described that correlates the amide H-1 and N-15 resonances of one residue simultaneously with both the C-13-alpha and C-13-beta resonances of its preceding residue. Sensitivity of the new experiment is comparable with that of the HN(CO)CA experiment (Bax, A.; Ikura, M. J. Biomol. NMR 1991, 1, 99-105), but the additional correlation to the C(beta) resonance of the preceding residue provides invaluable assignment information, previously inaccessible. The technique is demonstrated for interferon-gamma, a homodimeric protein of 31.4 kDa, enriched uniformly with C-13 and N-15. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. NR 18 TC 804 Z9 810 U1 2 U2 28 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUL 29 PY 1992 VL 114 IS 16 BP 6291 EP 6293 DI 10.1021/ja00042a003 PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA JF871 UT WOS:A1992JF87100003 ER PT J AU JONES, CM ANSARI, A HENRY, ER CHRISTOPH, GW HOFRICHTER, J EATON, WA AF JONES, CM ANSARI, A HENRY, ER CHRISTOPH, GW HOFRICHTER, J EATON, WA TI SPEED OF INTERSUBUNIT COMMUNICATION IN PROTEINS SO BIOCHEMISTRY LA English DT Article ID CONFORMATIONAL-CHANGES; LASER PHOTOLYSIS; HUMAN-HEMOGLOBIN; CARBOXYHEMOGLOBIN; RECOMBINATION; COOPERATIVITY; DYNAMICS; SPECTRA AB To determine the speed of communication between protein subunits, time-resolved absorption spectra were measured following partial photodissociation of the carbon monoxide complex of hemoglobin. The experiments were carried out using linearly polarized, 10-ns laser pulses, with the polarization of the excitation pulse both parallel and perpendicular to the polarization of the probe pulse. The substantial contribution to the observed spectra from photoselection effects was eliminated by isotropically averaging the polarized spectra, allowing a detailed comparison of the kinetics as a function of the degree of photolysis. These results show that prior to 1-mu-s both geminate ligand rebinding and conformational relaxation are independent of the number of ligands dissociated from the hemoglobin tetramer, as expected for a two-state allosteric model. After this time the kinetics depend on the ligation state of the tetramer. The conformational relaxation at 10-mu-s can be interpreted in terms of the two-state allosteric model as arising from the R to T quaternary conformational change of both unliganded and singly liganded molecules. These results suggest that communication between subunits requires about 1-mu-s and that the mechanism of the communication which occurs after this time is via the R to T conformational change. The optical anisotropy provides a novel means of accurately determining the extinction coefficients of the transient photoproduct. The decay in the optical anisotropy, moreover, provides an accurate determination of the rotational correlation time of 36 +/- 3 ns. C1 NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892. RI Henry, Eric/J-3414-2013 OI Henry, Eric/0000-0002-5648-8696 NR 28 TC 68 Z9 68 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 JUL 28 PY 1992 VL 31 IS 29 BP 6692 EP 6702 DI 10.1021/bi00144a008 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JF654 UT WOS:A1992JF65400008 PM 1637808 ER PT J AU CENCIARELLI, C HOHMAN, RJ ATKINSON, TP GUSOVSKY, F WEISSMAN, AM AF CENCIARELLI, C HOHMAN, RJ ATKINSON, TP GUSOVSKY, F WEISSMAN, AM TI EVIDENCE FOR GTP-BINDING PROTEIN INVOLVEMENT IN THE TYROSINE PHOSPHORYLATION OF THE T-CELL RECEPTOR ZETA-CHAIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID CYTOPLASMIC FREE CALCIUM; ANTIGEN RECEPTOR; SIGNAL TRANSDUCTION; MONOCLONAL-ANTIBODIES; PHOSPHOLIPASE-C; ACTIVATION; COMPLEX; POLYPEPTIDE; KINASE AB The zeta-subunit of the T cell receptor (TCR) is a prominent substrate for a TCR-activated tyrosine kinase. Tyrosine phosphorylation of the zeta-subunit in response to antibody-mediated receptor cross-linking was synergized in permeabilized T cells by either of two nonhydrolyzable GTP analogues, guanosine 5'-[gamma-thio]triphosphate (GTP-gamma-S) or guanosine 5'-[beta, gamma-imido]triphosphate Gpp(NH)p. ATP analogues did not significantly affect antibody-induced tyrosine phosphorylation. Unlike the GTP analogues, the GDP analogue guanosine 5'-[beta-thio]diphosphate (GDP-beta-S) did not enhance phosphorylation of zeta. The effect induced by the GTP analogues required TCR occupancy and was independent of protein kinase C. Taken together these observations implicate a GTP-binding protein in the modulation of TCR-induced tyrosine phosphorylation. C1 NCI,EXPTL IMMUNOL BRANCH,BLDG 10,RM 4B17,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,ALLERG DIS SECT,BETHESDA,MD 20892. NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NR 41 TC 15 Z9 15 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 JUL 25 PY 1992 VL 267 IS 21 BP 14527 EP 14530 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JF088 UT WOS:A1992JF08800004 PM 1386076 ER PT J AU TAKEUCHI, Y YANAGISHITA, M HASCALL, VC AF TAKEUCHI, Y YANAGISHITA, M HASCALL, VC TI METABOLIC PATHWAYS OF HEPARAN-SULFATE PROTEOGLYCANS IN A RAT PARATHYROID CELL-LINE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR-MEDIATED ENDOCYTOSIS; CULTURE; TRANSPORT; CALCIUM AB The distribution of heparan sulfate (HS) proteoglycans in clonal rat parathyroid cells is regulated by the extracellular Ca2+ concentration, which is a principal factor for parathyroid cell function (Takeuchi, Y., Sakaguchi, K., Yanagishita, M., Aurbach, G. D., and Hascall, V. C. (1990) J. Biol. Chem. 265, 13661-13668). Increasing the concentration of extracellular Ca2+ in the physiological range redistributes HS proteoglycans from the cell surface to an intracellular compartment. We have now examined effects of the extracellular Ca2+ concentration on the metabolism of the HS proteoglycans in detail using [S-35]sulfate metabolic labeling-chase experiments. Two distinct metabolic pathways were demonstrated: (i) the intracellular generation of HS chains from HS proteoglycans in prelysosomal compartments followed by their release into the medium (pathway 1), and (ii) intracellular generation of HS oligosaccharides from HS chains in prelysosomal compartments, which are eventually degraded into free sulfate in lysosomes (pathway 2). The HS oligosaccharides were exclusively present within the cells, whereas HS chains were found primarily in the medium. The cells do not internalize either HS proteoglycans or HS chains from the medium. These observations indicate that these two degradation pathways are independent. In addition to these pathways, approximately 15% of the HS proteoglycans were released into the medium as a proteoglycan form. Treatment of cells with chloroquine, a lysosomotropic agent, did not affect generation of HS chains but inhibited conversion of HS chains to HS oligosaccharides or to free sulfate and resulted in the release of HS chains from the cells. The drug did not affect metabolic pathway 1. The extracellular Ca2+ concentration did not alter these intracellular degradation pathways for HS proteoglycans in the parathyroid cells. Thus, extracellular Ca2+ appears to regulate only the distribution of HS proteoglycans between the cell surface and intracellular compartments, and the process of cycling between these compartments when extracellular Ca2+ is low. C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. NR 22 TC 15 Z9 15 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 JUL 25 PY 1992 VL 267 IS 21 BP 14677 EP 14684 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JF088 UT WOS:A1992JF08800030 PM 1634513 ER PT J AU TAKEUCHI, Y YANAGISHITA, M HASCALL, VC AF TAKEUCHI, Y YANAGISHITA, M HASCALL, VC TI RECYCLING OF TRANSFERRIN RECEPTORS AND HEPARAN-SULFATE PROTEOGLYCANS IN A RAT PARATHYROID CELL-LINE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MEDIATED ENDOCYTOSIS; CALCIUM; SECRETION; TRANSPORT; PROTEINS; SURFACE; COMPARTMENTS; MICROTUBULES; MEMBRANE; PATHWAYS AB We examined recycling of heparan sulfate (HS) proteoglycans and transferrin receptor (Tf-R) in a rat parathyroid cell line. While extracellular Ca2+ concentration ([Ca2+]e) regulates the recycling of HS proteoglycans in parathyroid cells, such that HS proteoglycans only recycle when [Ca2+]e is lowered below physiological levels, recycling of Tf-R occurs equally well both in 0.05 mM (low) and 2 mM (high) [Ca2+]e. Inhibiting endocytosis chemically with phenylarsine oxide or at low temperature (4-degrees-C) did not abolish the effects of changing [Ca2+], on HS proteoglycans in the recycling compartment even though transport of HS proteoglycans from the Golgi complex to the cell surface was inhibited in low [Ca2+]e. Microtubules are not involved in the recycling of HS proteoglycans or of Tf-R since nocodazole did not affect these processes. Inhibiting the increase of intracellular Ca2+ by an intracellular Ca2+ chelator sustained recycling of HS proteoglycans even in the presence of high [Ca2+]e. These observations show that the exocytosis pathway of HS proteoglycans in the recycling compartment is specifically regulated by [Ca2+]e, whereas that for constitutive secretion is not. Therefore, the recycling of HS proteoglycans may be directly related to some functions of parathyroid cells regulated by [Ca2+]e. Although the mechanism by which [Ca2+], regulates the exocytosis and recycling of HS proteoglycans is uncertain, it is suggested that an increase of intracellular Ca2+ is necessary, but not necessarily sufficient, for inhibiting their exocytosis. C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. NR 19 TC 12 Z9 12 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 JUL 25 PY 1992 VL 267 IS 21 BP 14685 EP 14690 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JF088 UT WOS:A1992JF08800031 PM 1634514 ER PT J AU LEEBEEK, FWG KARIYA, K SCHWABE, M FOWLKES, DM AF LEEBEEK, FWG KARIYA, K SCHWABE, M FOWLKES, DM TI IDENTIFICATION OF A RECEPTOR-BINDING SITE IN THE CARBOXYL TERMINUS OF HUMAN INTERLEUKIN-6 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COLONY-STIMULATING FACTOR; GROWTH-FACTOR; MONOCLONAL-ANTIBODY; LYMPHOCYTES-T; AMINO-ACIDS; HUMAN IL-6; PROTEIN; INTERFERON-BETA-2; MUTAGENESIS; EXPRESSION AB To identify a receptor binding site of human interleukin-6 (IL-6), we created a library of IL-6 variants with single amino acid substitutions in the last 15 residues (171-185) in the COOH terminus of IL-6. Twenty-seven IL-6 variants were tested for biological activity on a human hepatoma and a mouse hybridoma cell line. Most variants were additionally tested in a receptor binding assay using a human myeloma cell line. Several single amino acid substitutions in the COOH terminus of IL-6 were found to decrease biological activity significantly. This is especially seen in variants with amino acid substitutions that alter the postulated amphipathical alpha-helix structure between residues 178 and 183. The two highly conserved Arg residues at positions 180 and 183 seem to play a very important role in biological activity. The loss of biological activity in all inactive variants is completely paralleled by a decrease of IL-6 receptor binding, as determined by competition binding experiments. One mutant (Leu171) displayed a higher activity on human cells and a higher binding affinity to the receptor and can be considered an IL-6 agonist. It is concluded that the amphipathical alpha-helix structure in the COOH terminus of IL-6 is critical for ligand receptor interaction. Furthermore, the region between residues Ser178 and Arg183 (Ser-Leu-Arg-Ala-X-Arg) is identified as a receptor binding site in the COOH terminus of human IL-6. C1 UNIV N CAROLINA,DEPT PATHOL,CHAPEL HILL,NC 27599. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. FU NHLBI NIH HHS [HL31012] NR 53 TC 63 Z9 63 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 JUL 25 PY 1992 VL 267 IS 21 BP 14832 EP 14838 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JF088 UT WOS:A1992JF08800051 PM 1321818 ER PT J AU KIM, SJ KIM, KY TAPSCOTT, SJ WINOKUR, TS PARK, K FUJIKI, H WEINTRAUB, H ROBERTS, AB AF KIM, SJ KIM, KY TAPSCOTT, SJ WINOKUR, TS PARK, K FUJIKI, H WEINTRAUB, H ROBERTS, AB TI INHIBITION OF PROTEIN PHOSPHATASES BLOCKS MYOGENESIS BY 1ST ALTERING MYOD BINDING-ACTIVITY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSFORMING GROWTH-FACTOR; OKADAIC ACID; TUMOR-PROMOTER; MUSCLE DIFFERENTIATION; NUCLEAR FACTOR; GENE FAMILY; PHOSPHORYLATION; CELLS; ACTIVATION; EXPRESSION AB To examine the role of protein phosphatases in skeletal muscle differentiation, C2C12 myoblasts were treated with okadaic acid, a potent in vitro inhibitor of protein phosphatases 1 and 2A which regulate various cellular events in intact cells. We now show that okadaic acid treatment of the mouse myoblast C2C12 cell line reversibly altered the morphology of the cells and blocked differentiation. At a molecular level, it extinguished expression of the myogenic determination genes, MyoD1 and myogenin, but induced the expression of an inhibitor of differentiation, Id. Analysis of the MyoD1 promoter showed that inhibition of MyoD1 expression by okadaic acid occurs at the transcriptional level. These changes occur 10-20 h after okadaic acid treatment. However, within 1 h of treatment the ability of muscle extracts to support a specific MyoD-dependent gel mobility shift using a MyoD DNA binding site is lost. These data suggest that protein phosphatases play an important role during myogenic differentiation. C1 FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. NATL CANC CTR,RES INST,TOKYO 104,JAPAN. RP KIM, SJ (reprint author), NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892, USA. NR 43 TC 46 Z9 46 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 JUL 25 PY 1992 VL 267 IS 21 BP 15140 EP 15145 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JF088 UT WOS:A1992JF08800093 PM 1321827 ER PT J AU GOTO, Y DESILVA, MG TOSCANI, A PRABHAKAR, BS NOTKINS, AL LAN, MS AF GOTO, Y DESILVA, MG TOSCANI, A PRABHAKAR, BS NOTKINS, AL LAN, MS TI A NOVEL HUMAN INSULINOMA-ASSOCIATED CDNA, IA-1, ENCODES A PROTEIN WITH ZINC-FINGER DNA-BINDING MOTIFS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR-IIIA; MOLECULAR-CLONING; NUCLEOTIDE-SEQUENCE; G0/G1 TRANSITION; C-FOS; GENE; POLYPEPTIDE; CELLS; CLONES; REGION AB A subtraction library was constructed from human insulinoma (beta-cell tumor) and glucagonoma (alpha-cell tumor) cDNA phagemid libraries. Differential screening of 153 clones with end-labeled mRNAs from insulinoma, glucagonoma, and HeLa cells resulted in the isolation of a novel cDNA clone designated IA-1. This cDNA clone has a 2838-base pair sequence consisting of an open reading frame of 1530 nucleotides, which translates into a protein of 510 amino acids with a pI value of 9.1 and a molecular mass of 52,923 daltons. At the 3'-untranslated region there are seven ATTTA sequences between two polyadenylation signals (AATAAA). The IA-1 protein can be divided into two domains based upon the features of its amino acid sequence. The NH2-terminal domain of the deduced protein sequence (amino acids 1-250) has four classical pro-hormone dibasic conversion sites and an amidation signal sequence, Pro-Gly-Lys-Arg. The COOH-terminal domain (amino acids 251-510) contains five putative "zinc-finger" DNA-binding motifs of the form X3-Cys-X2-4-Cys-X12-His-X3-4-His-X4 which has been described as a consensus sequence for members of the Cys2-His2 DNA-binding protein class. Northern blot analysis revealed IA-1 mRNA in five of five human insulinoma and three of three murine insulinoma cell lines. Expression of this gene was undetectable in normal tissues. Additional tissue studies revealed that the message is expressed in several tumor cell lines of neuroendocrine origin including pheochromocytoma, medullary thyroid carcinoma, insulinoma, pituitary tumor, and small cell lung carcinoma. The restricted tissue distribution and unique sequence motifs suggest that this novel cDNA clone may encode a protein associated with the transformation of neuroendocrine cells. C1 NIDR,ORAL MED LAB,BLDG 30,RM 121,BETHESDA,MD 20892. NR 33 TC 77 Z9 80 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 25 PY 1992 VL 267 IS 21 BP 15252 EP 15257 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JF088 UT WOS:A1992JF08800109 PM 1634555 ER PT J AU LIPSCHIK, GY GILL, VJ LUNDGREN, JD ANDRAWIS, VA NELSON, NA NIELSEN, JO OGNIBENE, FP KOVACS, JA AF LIPSCHIK, GY GILL, VJ LUNDGREN, JD ANDRAWIS, VA NELSON, NA NIELSEN, JO OGNIBENE, FP KOVACS, JA TI IMPROVED DIAGNOSIS OF PNEUMOCYSTIS-CARINII INFECTION BY POLYMERASE CHAIN-REACTION ON INDUCED SPUTUM AND BLOOD SO LANCET LA English DT Article ID AEROSOLIZED PENTAMIDINE; BRONCHOALVEOLAR LAVAGE; MONOCLONAL-ANTIBODIES; PNEUMONIA; DNA; STAIN AB Detection of Pneumocystis carinii by the polymerase chain reaction (PCR) may facilitate non-invasive diagnosis of P carinii pneumonia and study of its epidemiology. We have compared the sensitivity and specificity of two PCR methods with those of conventional staining for detection of P carinii in induced sputum, bronchoalveolar lavage fluid (BAL), and blood. Of 71 sputum samples, 17 were from patients with microbiologically confirmed P carinii pneumonia. A nested PCR method correctly identified the presence of P carinii in all 17 (100% sensitive, 95% confidence interval [CI] 81-100%) and found no organisms in 50 of 54 microbiologically negative samples (93% specific, 95% CI 82-98%). PCR with a single primer pair was 71 % sensitive (44-90%) and 94% specific (85-99%). The sensitivity of conventional staining methods (direct and indirect fluorescence antibody and toluidine-blue-O tests) was significantly less (38-53%) than that of nested PCR (p<0.05). In BAL, neither PCR method was significantly better than the conventional staining methods. P carinii was detected in BAL or sputum from 10 immunocompromised patients without microbiological evidence of P carinii pneumonia, which suggests that symptom-free carriers or subclinical infection can exist. P carinii was detected by nested PCR in blood from 2 of 3 patients with disseminated pneumocystosis but in only 1 of 11 patients with P carinii infection restricted to the lungs. Nested PCR on induced sputum is more sensitive than conventional staining methods for the diagnosis of P carinii pneumonia and provides a non-invasive method of detecting disseminated disease. C1 NIH,WARREN G MAGNUSON CLIN CTR,MICROBIOL LAB,BETHESDA,MD 20892. UNIV COPENHAGEN,HVIDOVRE HOSP,DEPT INFECT DIS,DK-2650 HVIDOVRE,DENMARK. RP LIPSCHIK, GY (reprint author), NIH,DEPT CRIT CARE MED,WARREN G MAGNUSON CLIN CTR,BLDG 10,ROOM 7D43,BETHESDA,MD 20892, USA. OI Lundgren, Jens/0000-0001-8901-7850 NR 23 TC 139 Z9 148 U1 1 U2 3 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUL 25 PY 1992 VL 340 IS 8813 BP 203 EP 206 DI 10.1016/0140-6736(92)90469-J PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA JE758 UT WOS:A1992JE75800004 PM 1353136 ER PT J AU FALZON, M KUFF, EL AF FALZON, M KUFF, EL TI THE NUCLEOTIDE-SEQUENCE OF A MOUSE CDNA-ENCODING THE 80 KDA SUBUNIT OF THE KU-(P70 P80) AUTOANTIGEN SO NUCLEIC ACIDS RESEARCH LA English DT Note ID AUTO-ANTIGEN; PROTEIN; AUTOANTIBODIES; OVERLAP; CLONING RP FALZON, M (reprint author), NCI,BIOCHEM LAB,BLDG 37,ROOM 4C03,BETHESDA,MD 20892, USA. NR 7 TC 16 Z9 17 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 JUL 25 PY 1992 VL 20 IS 14 BP 3784 EP 3784 DI 10.1093/nar/20.14.3784 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JG812 UT WOS:A1992JG81200037 PM 1641347 ER PT J AU FREO, U HOLLOWAY, HW KALOGERAS, K RAPOPORT, SI SONCRANT, TT AF FREO, U HOLLOWAY, HW KALOGERAS, K RAPOPORT, SI SONCRANT, TT TI ADRENALECTOMY OR METYRAPONE-PRETREATMENT ABOLISHES CEREBRAL METABOLIC RESPONSES TO THE SEROTONIN AGONIST 1-(2,5-DIMETHOXY-4-IODOPHENYL)-2-AMINOPROPANE (DOI) IN THE HIPPOCAMPUS SO BRAIN RESEARCH LA English DT Article DE ADRENALECTOMY; METYRAPONE; SEROTONIN; 1-(2,5-DIMETHOXY-4-IODOPHENYL)-2-AMINOPROPANE; HIPPOCAMPUS; CEREBRAL METABOLISM ID CORTICOTROPIN-RELEASING FACTOR; RAT-BRAIN; GLUCOSE-UTILIZATION; CORTICOSTERONE SYNTHESIS; RECEPTOR AGONIST; AWAKE RATS; STRESS; GLUCOCORTICOIDS; ADAPTATION; HYPOTHESIS AB 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a serotonin type 2 (5-HT2) agonist, elevates plasma corticosterone levels and reduces the cerebral metabolic rate for glucose (rCMRglc) in the hippocampus, a structure which possesses few 5-HT2 receptors but a large number of steroid receptors. To explore the hypothetical interaction between 5-HT and steroid mechanisms in the hippocampus, we measured rCMRglc in intact, adrenalectomized and metyrapone-pretreated rats after saline or DOI administration. Metyrapone pretreatment alone had no significant effect on rCMRglc, but adrenalectomy produced widespread rCMRglc increases in the cortex, hippocampus and monoaminergic brainstem nuclei. In intact rats, DOI 10 mg/kg reduced rCMRglc in limbic areas and increased it in the interanteromedial and paracentral thalamic nuclei. Metyrapone pretreatment and adrenalectomy abolished rCMRglc responses to DOI in hippocampal areas and enhanced those in thalamic nuclei. These results indicate that brain responses to DOI are dependent upon the functional state of the hypothalamus-pituitary-adrenal cortex axis. C1 NIA,NEUROSCI LAB,BLDG 10,ROOM 6C103,BETHESDA,MD 20892. NIMH,NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 62 TC 38 Z9 38 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 JUL 24 PY 1992 VL 586 IS 2 BP 256 EP 264 DI 10.1016/0006-8993(92)91634-Q PG 9 WC Neurosciences SC Neurosciences & Neurology GA JH781 UT WOS:A1992JH78100010 PM 1521159 ER PT J AU SHIMODA, K SAUVE, Y MARINI, A SCHWARTZ, JP COMMISSIONG, JW AF SHIMODA, K SAUVE, Y MARINI, A SCHWARTZ, JP COMMISSIONG, JW TI A HIGH PERCENTAGE YIELD OF TYROSINE HYDROXYLASE-POSITIVE CELLS FROM RAT E14-MESENCEPHALIC CELL-CULTURE SO BRAIN RESEARCH LA English DT Article DE ASTROCYTE; DOPAMINE; DOPAMINE UPTAKE; DOPAMINE RELEASE; GLIAL FIBRILLARY ACIDIC PROTEIN; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; IMMUNOHISTOCHEMISTRY; MESENCEPHALIC DOPAMINERGIC NEURON; NEUROTROPHIC FACTOR; TISSUE CULTURE; TYROSINE HYDROXYLASE ID MESENCEPHALIC DOPAMINERGIC-NEURONS; TRANSECTED SPINAL-CORD; NERVE GROWTH-FACTOR; ADULT-RAT; INVITRO MATURATION; STIMULATION; RELEASE; BRAIN; EXPRESSION; OUTGROWTH AB In the ventral mesencephalon of the E14 rat fetus, 90% of the dopaminergic, tyrosine hydroxylase positive (TH+) cells are localized in 1.0 mm3 of tissue. This same ventral mesencephalic region also contains 90% of the dopamine content of the E14 ventral brainstem (2.2+/-0.3 nmol/mg protein). When cells were prepared for culturing from this localized area, and plated at a density of 2.5 x 10(5) cells/cm2, 17-21% of the cells were TH+, at 4 and 12 h, and at 1, 5, 7 and 10 days after plating. The percentage of TH + cells was also 17-21% when examined at 4 h, 12 h or 5 days after plating at densities ranging from 7.8 x 10(3) to 2.5 x 10(5) cells/cm 2. However, cell survival at a density of < 6.2 x 10(4) cells/cm2 was poor after 5 days in culture. Based on the degree of neurite elongation and complexity, cell maturation appeared to be complete at 5 days in culture (DIV5), and appeared to be maintained at this level up to DIV10. By DIV14, neurite retraction was evident, and the cells were more rounded. These signs may indicate the inception of senescence in the cultures. A benztropine-sensitive, concentration-dependent dopamine uptake mechanism was demonstrated in the cultures at DIV7, and DA could be released from preloaded cells using 50 mM K+. Five morphological subtypes of TH+ cells were identified in the cultures. This primary culture of the ventral mesencephalic, dopaminergic area, with a high percentage of TH+ cells, is suitable for use in acute biochemical and cellular studies, between DIV5 and DIV10. C1 NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,BIOCHEM GENET LAB,WASHINGTON,DC 20032. MCGILL UNIV,DEPT PHYSIOL,MONTREAL H3A 2T5,QUEBEC,CANADA. NINCDS,CNB,BETHESDA,MD 20814. NINCDS,LMCN,BETHESDA,MD 20814. NR 36 TC 70 Z9 84 U1 1 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 JUL 24 PY 1992 VL 586 IS 2 BP 319 EP 331 DI 10.1016/0006-8993(92)91642-R PG 13 WC Neurosciences SC Neurosciences & Neurology GA JH781 UT WOS:A1992JH78100018 PM 1355697 ER PT J AU MIZUUCHI, M BAKER, TA MIZUUCHI, K AF MIZUUCHI, M BAKER, TA MIZUUCHI, K TI ASSEMBLY OF THE ACTIVE FORM OF THE TRANSPOSASE-MU DNA COMPLEX - A CRITICAL CONTROL POINT IN MU-TRANSPOSITION SO CELL LA English DT Article ID STRAND-TRANSFER-REACTION; INTEGRATION HOST FACTOR; BACTERIOPHAGE-MU; PHAGE-MU; B-PROTEIN; SITE; ENHANCER; ENDS; TRANSPOSOSOMES; RECOMBINATION AB Discovery and characterization of a new intermediate in Mu DNA transposition allowed assembly of the transposition machinery to be separated from the chemical steps of recombination. This stable intermediate, which accumulates in the presence of Ca2+, consists of the two ends of the Mu DNA synapsed by a tetramer of the Mu transposase. Within this stable synaptic complex (SSC), the recombination sites are engaged but not yet cleaved. Thus, the SSC is structurally related to both the cleaved donor and strand transfer complexes, but precedes them on the transposition pathway. Once the active protein-DNA complex is constructed, it is conserved throughout transposition. The participation of internal sequence elements and accessory factors exclusively during SSC assembly allows recombination to be controlled prior to the irreversible chemical steps. RP MIZUUCHI, M (reprint author), NIDDK,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 39 TC 144 Z9 145 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUL 24 PY 1992 VL 70 IS 2 BP 303 EP 311 DI 10.1016/0092-8674(92)90104-K PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JE757 UT WOS:A1992JE75700013 PM 1322248 ER PT J AU FIELD, MJ AF FIELD, MJ TI A MOLECULAR-DYNAMICS SIMULATION OF PHOTOINDUCED ELECTRON-TRANSFER IN AN ORGANIC DONOR-ACCEPTOR COMPOUND SO CHEMICAL PHYSICS LETTERS LA English DT Article ID POLAR-SOLVENTS; MODEL; PROTEINS AB The results of a molecular dynamics simulation are presented of the photo-induced excitation and accompanying electron transfer in a rigid organic bichromophoric compound in vacuum. A semi-classical algorithm is used in which the energies of the two lowest electronic states of the molecules are described with a semi-empirical quantum-mechanical method and the dynamics of the nuclei are treated classically. The model shows that the excited state can become significantly occupied on the experimentally observed timescale, although the populations of each state are sensitive to the parameters defining the radiation field and the coupling between the field and the molecule. RP FIELD, MJ (reprint author), NIH,DIV COMP RES & TECHNOL,BLDG 12A,ROOM 2007,BETHESDA,MD 20892, USA. NR 25 TC 1 Z9 1 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-2614 J9 CHEM PHYS LETT JI Chem. Phys. Lett. PD JUL 24 PY 1992 VL 195 IS 4 BP 388 EP 392 DI 10.1016/0009-2614(92)85622-H PG 5 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA JH380 UT WOS:A1992JH38000019 ER PT J AU QUACH, TT DUCHEMIN, AM OLIVER, AP SCHRIER, BK WYATT, RJ AF QUACH, TT DUCHEMIN, AM OLIVER, AP SCHRIER, BK WYATT, RJ TI HYDRA HEAD ACTIVATOR PEPTIDE HAS TROPHIC ACTIVITY FOR EUKARYOTIC NEURONS SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE HEAD ACTIVATOR PEPTIDE; NEUROTROPHIC FACTOR; SYMPATHETIC GANGLION CELL; DORSAL ROOT GANGLION CELL; NEUROBLASTOMA CELL ID VASOACTIVE-INTESTINAL-PEPTIDE; AMINO-ACID-SEQUENCE; MORPHOLOGICAL-DIFFERENTIATION; NEURITE EXTENSION; BLASTOMA CELLS; GROWTH-FACTOR; RAT-BRAIN; NEUROPEPTIDE; SURVIVAL; INVITRO AB The synthetic undecameric peptide, pGlu-Pro-Pro-Gly-Gly-Ser-Lys-Val-Ile-Leu-Phe, known as the hydra head activator peptide, present in high concentrations in mammalian hypothalamus and intestine, was tested for neurotrophic activity in a survival assay using cultured chick embryonic sympathetic and dorsal root ganglion cells, and for morphological differentiation activity on neuroblastoma cells. Hydra head activator peptide supported neuron survival. The optimal active concentration, 1 pM, was very similar to the concentration that causes bud and. head formation in hydra. Maximal neuron survival obtained with hydra head activator peptide was close to that obtained with nerve growth factor: both substances enhanced survival up to 3 times that of control cultures. Bradykinin, which has some amino acid sequence homology with hydra head activator, was inactive as a neurotrophic factor. Hydra head activator induced rapid morphological differentiation of the mouse neuroblastoma cell line Neuro-2A. Neuro-2A responded to the peptide by process extension, 4 h after its addition to the culture medium. Neurotrophic factors isolated to date have been characterized by their ability to maintain cell viability and enhance neurite outgrowth. Hydra head activator peptide met these two criteria when tested in 3 different neuron culture systems. Our results suggest that the head activator peptide may act as a neurotrophic factor for neurons in other species, including mammals. C1 NICHHD,DEV NEUROBIOL LAB,MOLEC NEUROBIOL UNIT,BETHESDA,MD 20892. NIMH,NEUROSCI CTR ST ELIZABETH,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. NR 27 TC 6 Z9 6 U1 0 U2 0 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 JUL 24 PY 1992 VL 68 IS 1 BP 97 EP 102 DI 10.1016/0165-3806(92)90251-Q PG 6 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA JK050 UT WOS:A1992JK05000011 ER PT J AU WELLER, JL KLEIN, DC AF WELLER, JL KLEIN, DC TI THE PINEAL ADRENERGIC -] CYCLIC-GMP RESPONSE DEVELOPS 2 WEEKS AFTER THE ADRENERGIC -] CYCLIC-AMP RESPONSE SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Note DE CYCLIC GMP; PINEAL; GUANYLATE CYCLASE; ADRENERGIC ID PROTEIN KINASE-C; SEROTONIN N-ACETYLTRANSFERASE; INTESTINAL PEPTIDE STIMULATION; RAT PINEALOCYTES; GUANOSINE 3',5'-MONOPHOSPHATE; CGMP ACCUMULATION; ALPHA-1-ADRENERGIC POTENTIATION; ADENOSINE-3',5'-MONOPHOSPHATE; ACTIVATION; CALCIUM AB Pineal metabolism is regulated primarily by noradrenergic innervation. Stimulation of the adult gland with norepinephrine elevates both cyclic AMP and cyclic GMP production, through remarkably similar mechanisms requiring activation of both beta- and alpha-1-adrenergic receptors. As described here, however, the adrenergic stimulation of cyclic GMP is first detectable about 2 weeks after the cyclic AMP response can be detected. This indicates there is a profound difference in when cyclic AMP-and cyclic GMP-regulated processes can be adrenergically regulated. C1 NICHHD,DEV NEUROBIOL LAB,NEUROENDOCRINOL SECT,BLDG 36,ROOM 4A07,BETHESDA,MD 20892. NR 32 TC 9 Z9 9 U1 0 U2 0 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 JUL 24 PY 1992 VL 68 IS 1 BP 144 EP 147 DI 10.1016/0165-3806(92)90258-X PG 4 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA JK050 UT WOS:A1992JK05000018 ER PT J AU KASHMAN, Y GUSTAFSON, KR FULLER, RW CARDELLINA, JH MCMAHON, JB CURRENS, MJ BUCKHEIT, RW HUGHES, SH CRAGG, GM BOYD, MR AF KASHMAN, Y GUSTAFSON, KR FULLER, RW CARDELLINA, JH MCMAHON, JB CURRENS, MJ BUCKHEIT, RW HUGHES, SH CRAGG, GM BOYD, MR TI HIV INHIBITORY NATURAL-PRODUCTS .7. THE CALANOLIDES, A NOVEL HIV-INHIBITORY CLASS OF COUMARIN DERIVATIVES FROM THE TROPICAL RAIN-FOREST TREE, CALOPHYLLUM-LANIGERUM SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID REVERSE-TRANSCRIPTASE INHIBITORS; ANTIVIRAL ACTIVITY; ESCHERICHIA-COLI; MOSHER METHOD; SRI-LANKA; DITERPENES; REPLICATION; CALABA; POTENT AB Eight new coumarin compounds (1-8) were isolated by anti-HIV bioassay-guided fractionation of an extract of Calophyllum lanigerum. The structures of calanolide A (1), 12-acetoxycalanolide A (2), 12-methyoxycalanolide A (3), calanolide B (4), 12-methoxycalanolide B (5), calanolide C (6) and related derivatives 7 and 8 were solved by extensive spectroscopic analyses, particularly HMQC, HMBC, and difference NOE NMR experiments. The absolute stereochemistry of calanolide A (1) and calanolide B (4) was established by a modified Mosher's method. Calanolides A (1) and B (4) were completely protective against HIV-1 replication and cytopathicity (EC50 values of 0.1-mu-M and 0.4-mu-M, respectively), but were inactive against HIV-2. Some of the related compounds also showed evidence of anti-HIV-1 activity. Studies with purified bacterial recombinant reverse transcriptases (RT) revealed that the calanolides are HIV-1 specific RT inhibitors. Moreover, calanolide A was active not only against the AZT-resistant G-9106 strain of HIV-1 but also against the pyridinone-resistant A17 strain. This was of particular interest since the A17 virus is highly resistant to previously known HIV-1 specific, non-nucleoside RT inhibitors (e.g., TIBO; BI-RG-587; L693,593) which comprise a structurally diverse but apparently common pharmacologic class. The calanolides represent a substantial departure from the known class and therefore provide a novel new anti-HIV chemotype for drug development. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. SO RES INST,BIRMINGHAM,AL 35255. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,NAT PROD BRANCH,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 39 TC 380 Z9 415 U1 3 U2 33 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 JUL 24 PY 1992 VL 35 IS 15 BP 2735 EP 2743 DI 10.1021/jm00093a004 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA JF496 UT WOS:A1992JF49600004 PM 1379639 ER PT J AU CARROLL, FI ABRAHAM, P PARHAM, K BAI, X ZHANG, X BRINE, GA MASCARELLA, SW MARTIN, BR MAY, EL SAUSS, C DIPAOLO, L WALLACE, P WALKER, JM BOWEN, WD AF CARROLL, FI ABRAHAM, P PARHAM, K BAI, X ZHANG, X BRINE, GA MASCARELLA, SW MARTIN, BR MAY, EL SAUSS, C DIPAOLO, L WALLACE, P WALKER, JM BOWEN, WD TI ENANTIOMERIC N-SUBSTITUTED N-NORMETAZOCINES - A COMPARATIVE-STUDY OF AFFINITIES AT SIGMA, PCP, AND MU OPIOID RECEPTORS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID GUINEA-PIG BRAIN; PHENCYCLIDINE-LIKE; SQUIRREL-MONKEYS; HIGHLY POTENT; BINDING; SITES; ALLYLNORMETAZOCINE; DRUGS; RAT; IDENTIFICATION AB The optical antipodes of N-allyl-N-normetazocine (2; SKF 10047, NANM) were the original compounds used for the classification of the sigma-receptor as distinct from other receptors such as the PCP (NMDA), opioid, and dopamine receptors. Later studies showed that (+)-N-(dimethylallyl)-N-normetazocine [(+)-4, (+)-pentazocine] was more potent and selective for the sigma-receptor. In order to gain additional structure-activity relationship information, several N-substituted N-normetazocine analogs were prepared and evaluated for their sigma-1 ([H-3]-(+)-3-PPP or [H-3]-(+)-pentazocine), PCP ([H-3]TCP), and mu-opioid ([H-3]DAMGO) receptor binding affinities. (+)-N-Benzyl-N-normetazocine [(+)-10)] possessed subnanomolar affinities for the sigma-site, K(i) = 0.67. The analog (+)-10 showed > 14000- and 2400-fold selectivity, respectively, for the sigma-receptor relative to the PCP and mu-opioid receptors. The N-substituted N-normetazocines were enantioselective for the sigma-site. The (+)-N-benzyl analog, (+)-10, showed a 55-fold selectivity relative to (-)-10. Analysis of the data also revealed that (+)-normetazocine [(+)-1] [K(i) = 30 nM] possessed the highest affinity for the PCP receptor. However, (+)-metazocine [(+)-5] (K(i) = 41 nM) was the most selective compound for the PCP receptor relative to the sigma (51-fold) and mu-opioid (> 200-fold) sites. C1 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PHARMACOL & TOXICOL,RICHMOND,VA 23298. NIDDK,MED CHEM LAB,BETHESDA,MD 20892. BROWN UNIV,DIV BIOL & MED,PROVIDENCE,RI 02912. BROWN UNIV,DEPT PSYCHOL,PROVIDENCE,RI 02912. RP CARROLL, FI (reprint author), RES TRIANGLE INST,RES TRIANGLE PK,NC 27709, USA. FU NIDA NIH HHS [DA05721, DA00490, DA02396] NR 35 TC 69 Z9 70 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUL 24 PY 1992 VL 35 IS 15 BP 2812 EP 2818 DI 10.1021/jm00093a014 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA JF496 UT WOS:A1992JF49600014 PM 1322987 ER PT J AU DECOSTA, BR IADAROLA, MJ ROTHMAN, RB BERMAN, KF GEORGE, C NEWMAN, AH MAHBOUBI, A JACOBSON, AE RICE, KC AF DECOSTA, BR IADAROLA, MJ ROTHMAN, RB BERMAN, KF GEORGE, C NEWMAN, AH MAHBOUBI, A JACOBSON, AE RICE, KC TI PROBES FOR NARCOTIC RECEPTOR MEDIATED PHENOMENA .18. EPIMERIC 6-ALPHA-IODO-3,14-DIHYDROXY-17-(CYCLOPROPYLMETHYL)-4,5-ALPHA-EPOXYMORPHI NANS AND 6-BETA-IODO-3,14-DIHYDROXY-17-(CYCLOPROPYLMETHYL)-4,5-ALPHA-EPOXYMORPHIN ANS AS POTENTIAL LIGANDS FOR OPIOID RECEPTOR SINGLE PHOTON-EMISSION COMPUTED-TOMOGRAPHY - SYNTHESIS, EVALUATION, AND RADIOCHEMISTRY OF [I-125] 6-BETA-IODO-3,14-DIHYDROXY-17-(CYCLOPROPYLMETHYL)-4,5-ALPHA-EPOXYMORPHIN AN SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID OPIATE ANTAGONIST CYCLOFOXY; C-11 CARFENTANIL BINDING; RAT-BRAIN; INACTIVE ENANTIOMERS; SUBTYPES INVITRO; SELECTIVE LIGAND; KINETIC-ANALYSIS; INVIVO; SITES; NORBINALTORPHIMINE AB The epimeric 6-beta- and 6-alpha-iodo-3,14-dihydroxy-17-(cyclopropylmethyl)-4,5-alpha-epoxymorphinans (1, ioxy) and (2, epioxy), respectively, were each synthesized in five steps starting with naltrexone. The configuration of the 6-iodo group of 1 was unequivocally determined to be beta-based on single crystal X-ray analysis of its precursor 3-acetoxy-6-beta-iodo-14-hydroxy-17-(cyclopropylmethyl)-4,5-alpha-epoxymorphinan (10). Both 1 and 2 as well as their corresponding 3-O-acetates 10 and 11 were found to readily cross the blood-brain barrier and completely reverse the analgesic effects of a 10 mg/kg intraperitoneal dose of morphine sulfate as determined by the paw withdrawal latency test. Compounds 1 and 2 were found to bind with high affinity to mu, delta, and kappa-receptors in vitro. In general, 1 and 2 exhibited higher affinity for mu and kappa-receptors than naltrexone while the 6-beta-iodo epimer 1 (ioxy) was more potent than its epimer 2. In a comparison of the 6-beta-halogen substituent on binding affinity across opioid receptor subtypes, it was generally found that I > Br > F. On the basis of the results of in vitro and in vivo testing, 1 was selected as a target for radioiodination and evaluation as a potential single photon emission computed tomography imaging agent for opioid receptors. Carrier-free [I-125]-1 was synthesized in near quantitative yield by the sequence of reaction of excess 3-acetoxy-6-alpha-[[(trifluoromethyl)sulfonyl]oxy]-14-hydroxy-17-(cyclopropylmethyl)-4,5-alpha-epoxymorphinan (8) with anhydrous (NaI)-I-125 in dry acetonitrile for 90 min at 76-degrees-C followed by deacetylation of the product with 1:1 aqueous ammonia/acetonitrile at 25-degrees-C. The potential of [I-125]-1 as an in vivo imaging agent for opioid receptors is evaluated and discussed. C1 NIDDKD,MED CHEM LAB,ROOM B1-23,BLDG 8,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NIDA,ADDICT RES CTR,PSYCHOBIOL LAB,BALTIMORE,MD 21224. NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. NIMH,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. USN,RES LAB,WASHINGTON,DC 20375. NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL LAB,BALTIMORE,MD 21224. NR 71 TC 30 Z9 30 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 JUL 24 PY 1992 VL 35 IS 15 BP 2826 EP 2835 DI 10.1021/jm00093a016 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA JF496 UT WOS:A1992JF49600016 PM 1322988 ER PT J AU WISE, SP AF WISE, SP TI MISTAKEN VIEW SO NATURE LA English DT Letter RP WISE, SP (reprint author), NIMH,NEUROPHYSIOL LAB,POOLESVILLE,MD 20837, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUL 23 PY 1992 VL 358 IS 6384 BP 272 EP 272 DI 10.1038/358272c0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JE684 UT WOS:A1992JE68400026 PM 1640992 ER PT J AU KIM, SJ WAGNER, S LIU, F OREILLY, MA ROBBINS, PD GREEN, MR AF KIM, SJ WAGNER, S LIU, F OREILLY, MA ROBBINS, PD GREEN, MR TI RETINOBLASTOMA GENE-PRODUCT ACTIVATES EXPRESSION OF THE HUMAN TGF-BETA-2 GENE THROUGH TRANSCRIPTION FACTOR ATF-2 SO NATURE LA English DT Article ID PROTEIN; BINDING; GROWTH; FAMILY; BETA AB THE retinoblastoma susceptibility gene product (pRb) plays an important role in constraining cellular proliferation and in regulating the cell cycle1,2. The pRb inhibits transcription of genes involved in growth control (reviewed in ref. 3) and can regulate transforming growth factor beta-1 (TGF-beta-1) gene expression4,5. TGF-beta isoforms also down-regulate cellular proliferation6,7. To determine whether pRb also regulates expression of other TGF-beta isoforms, we examined the effect of pRb on the expression of the human TGF-beta-2 gene. The human TGF-beta-2 promoter contains multiple elements including an ATF site, which is essential for basal promoter activity8. Here we report that pRb activates transcription of the human TGF-beta-2 gene. The promoter element responsible for pRb-mediated transcriptional regulation is a binding site for ATF proteins, an extensive transcription factor family9. We provide evidence that implicates ATF-2 in pRb-responsiveness. First, the ATF promoter element in the TGF-beta-2 gene is a high-affinity ATF-2-binding site. Second, a GAL4-ATF2 fusion protein can support pRb-mediated transcriptional activation of a promoter containing GAL4-binding sites. Third, ATF-2 in nuclear extracts can interact with pRb. Our results reveal a new mechanism by which pRb constrains cellular proliferation: by activating ex ression of the inhibitory growth factor, TGF-beta-2. C1 UNIV MASSACHUSETTS,MED CTR,PROGRAM MOLEC MED,WORCESTER,MA 01605. UNIV PITTSBURGH,SCH MED,DEPT MOLEC GENET & BIOCHEM,PITTSBURGH,PA 15261. RP KIM, SJ (reprint author), NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892, USA. NR 22 TC 248 Z9 251 U1 0 U2 3 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUL 23 PY 1992 VL 358 IS 6384 BP 331 EP 334 DI 10.1038/358331a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JE684 UT WOS:A1992JE68400064 PM 1641004 ER PT J AU ROGERS, WJ EPSTEIN, AE ARCINIEGAS, JG CROSSLEY, GH DAILEY, SM KAY, GN LITTLE, RE MACLEAN, WAH PAPAPIETRO, SE PLUMB, VJ SILBER, S BAKER, AR CARLISLE, K COHEN, N COX, M THOMAS, C LEVSON, L VONHAGEL, D WALTON, AE PRATT, CM MAHMARIAN, J MORRIS, G CAPONE, RJ BERGER, EE CHMIELEWSKI, C GORKIN, L KHAN, AH KORR, K HANDSHAW, K CONNOLLY, E FITZPATRICK, D CAMERON, T WYSE, DG DUFF, HJ MITCHELL, LB GILLIS, AM WARNICA, JW SHELDON, RS LESOWAY, NR KELLEN, J HALE, C INKSTER, M BRODSKY, M WOLFF, L ALLEN, B ZELMAN, R THOMAS, G CAUDILLO, G TAKEDA, D SHERWOOD, C RANAZZI, R RAPAPORT, E DOHRMANN, ML RASKIN, S DREW, DW SOMELOFSKI, CA DANFORTH, JW HUI, PY JOHNSON, MR LABARCA, JR WALDO, AL CARLSON, MD ADLER, DS HOLLAND, JB BUCHTER, CM BAHLER, RC PAMELIA, FX JOSEPHSON, RA HENTHORN, RW ZUELGARAY, JG WOOD, K REDMON, P VARGAS, MA VARGO, L SCHALLER, SE KOBUS, CE CHOBAN, NL BIGGER, JT GREENBERG, HM GREGORY, JJ HOCHMAN, JS RADOSLOVICH, G STEINBERG, JS ROTHBART, ST CASE, R DWYER, EM SQUATRITO, A KELLY, M CAMPION, JM TORMEY, D ANTHONY, R CALLAGHAN, E CHAPNICK, M RIPLEY, B FONTANA, C SCHLANT, RC ARENSBERG, D CORSO, JA HURST, JW MORRIS, DC SHERMAN, SW SILVERMAN, BD SILVERMAN, ME ROBERTS, JS BALLOU, SK JEFFRIES, VD BRACKNEY, BA SEALS, AA HARTLEY, J BAKER, RM GILMOUR, KE BAKER, SB HOWARD, J KATZ, RJ BESCH, GA BRILL, D DIBIANCO, R DONOHUE, D FISHER, G FRANCIS, C FRIEDMAN, D GOLDBERG, D GOLDBERG, S KOSS, G LARCA, L LEONARD, R LINDGREN, K RONAN, J ROSENBLATT, A ROSING, D ROSS, A ROTSZTAIN, A SHAWL, F SINDERSON, T STEVENSON, R TINKER, B VARGHESE, J YACKEE, J BIGHAM, H FRANKLIN, W GOLD, R GRAHAM, G GROSSBERG, D HOARE, R LEVY, W MAHMOOD, T TANNENBAUM, E TULLNER, W EISENHOWER, E GERACI, T WILHELMSEN, L BERGSTRAND, R FREDLUND, BO SIGURDSSON, A SIVERTSSON, R SWEDBERG, K HOULTZ, B WIKLUND, I SCHLYTER, G HEDELIN, G LEIJON, M MORGANROTH, J CARVER, J HOROWITZ, L KUTALEK, S PAPA, L SANDBERG, J VICTOR, M CESARE, S VRABEL, C TALARICO, K LUHMANN, S PALAZZO, D GOLDSTEIN, S GOLDBERG, AD FRUMIN, H WESTVEER, D DEBUTLIER, M SCHAIRER, J STOMEL, R FRANK, DM JARANDILLA, R DAVEY, D HASSE, C SHINNEY, S MORLEDGE, JH FARNHAM, DJ HINDERACKER, PH MUSSER, WE DEVRIES, K KUSHNER, JA RAO, R PETERSON, DT MCCAULEY, CS BERGEN, TS BOWMAN, KO GILLMAN, A FULLER, L OBRIEN, J MORLEDGE, J DEMARIA, AN KUO, CS KAMMERLING, JM CORUM, J THIEMANN, M SCHRODT, R PETERS, R SUTTON, F GOTTLIEB, S PAPUCHIS, G MATTIONI, T TODD, L CUSACK, C SCHECK, J HUANG, SKS ALPERT, JS GORE, JM RYAN, M COLLETTWILLEY, P CHAHINE, RA SEQUEIRA, RF LOWERY, MH DELGADO, LM CORREA, JL LASO, LJ HODGES, M SALERNO, D ANDERSON, B COLLINS, R DENES, P DUNBAR, D GRANRUD, G HAUGLAND, J HESSION, W MCBRIDE, J GORNICK, C SIMONSON, J TOLINS, M ETTINGER, A PETERSON, S SLIVKEN, R GRIMALDI, L ROY, D THEROUX, P LEMERY, R MORISSETTE, D BEAUDOIN, D GIRARD, L LAVALLEE, E MCANULTY, JH REINHART, SE MAURICE, G MURPHY, ES KRON, J MARCHANT, C BOXER, J PRINCEHOUSE, L SINNER, K BEANLANDS, D DAVIES, R GREEN, M WILLIAMS, W BAIRD, MJ GARRARD, L HEAL, S HASPECT, A BORTHWICK, J MAROIS, L WOODEND, K AKIYAMA, T HOOD, WB EASLEY, R RYAN, G KENIEN, G PATT, M KAZIERAD, D GOLDFARB, A BUTLER, LL KELLER, ML STANLEY, P PEEBLES, J SYROCKI, D LAVIN, D DENES, P SCHOENBERGER, JA LIEBSON, PR STAMATO, NJ PETROPULOS, AT BUCKINGHAM, TA REMIJAS, T KOCOUREK, J JANKO, K BARKER, AH ANDERSON, JL FOWLES, RE KEITH, TB WILLIAMS, CB MORENO, FL DORAN, EN FOWLER, B SUMMERS, K WHITE, C OHARA, G ROULEAU, JL PLANTE, S VINCENT, C BOUCHARD, D ZOBLE, RG OTERO, JE BUGNI, WJ SCHWARTZ, KM SHETTIGAR, UR BREWINGTON, JA UMBERGER, J COHEN, JD BJERREGAARD, P HAMILTON, WP GARNER, M ANDERSON, S ELSHERIF, N URSELL, SN GABOR, GE IBRAHIM, B ASSADI, M BREZSNYAK, ML PORTER, AV STANIORSKI, A WOOSLEY, RL RODEN, DM CAMPBELL, WB ECHT, DS LEE, JT MURRAY, KT SPELL, JD BONHOTAL, ST JARED, LL THOMAS, TI GOLDNER, F RICHARDSON, DW ROMHILT, DW ELLENBOGEN, KA BANE, BB FIELDS, J SHRADER, S POWELL, E CHAFFIN, CF WELLS, A CONWAY, KT PLATIA, EV ODONOGHUE, S TRACY, CM ALI, N BOWEN, P BROOKS, KM OETGEN, W WESTON, LT CARSON, P OBIASMANNO, D HARRISON, J SAYLOR, A POWELL, S HAAKENSON, CM SATHER, MR MALONE, LA HALLSTROM, AP MCBRIDE, R GREENE, HL BROOKS, MM LEDINGHAM, R REYNOLDSHAERTLE, RA HUTHER, M SCHOLZ, M MORRIS, M FRIEDMAN, LM SCHRON, E VERTER, J JENNINGS, C PROSCHAN, M BRISTOW, JD DEMETS, DL FISCH, C NIES, AS RUSKIN, J STRAUSS, H WALTERS, L AF ROGERS, WJ EPSTEIN, AE ARCINIEGAS, JG CROSSLEY, GH DAILEY, SM KAY, GN LITTLE, RE MACLEAN, WAH PAPAPIETRO, SE PLUMB, VJ SILBER, S BAKER, AR CARLISLE, K COHEN, N COX, M THOMAS, C LEVSON, L VONHAGEL, D WALTON, AE PRATT, CM MAHMARIAN, J MORRIS, G CAPONE, RJ BERGER, EE CHMIELEWSKI, C GORKIN, L KHAN, AH KORR, K HANDSHAW, K CONNOLLY, E FITZPATRICK, D CAMERON, T WYSE, DG DUFF, HJ MITCHELL, LB GILLIS, AM WARNICA, JW SHELDON, RS LESOWAY, NR KELLEN, J HALE, C INKSTER, M BRODSKY, M WOLFF, L ALLEN, B ZELMAN, R THOMAS, G CAUDILLO, G TAKEDA, D SHERWOOD, C RANAZZI, R RAPAPORT, E DOHRMANN, ML RASKIN, S DREW, DW SOMELOFSKI, CA DANFORTH, JW HUI, PY JOHNSON, MR LABARCA, JR WALDO, AL CARLSON, MD ADLER, DS HOLLAND, JB BUCHTER, CM BAHLER, RC PAMELIA, FX JOSEPHSON, RA HENTHORN, RW ZUELGARAY, JG WOOD, K REDMON, P VARGAS, MA VARGO, L SCHALLER, SE KOBUS, CE CHOBAN, NL BIGGER, JT GREENBERG, HM GREGORY, JJ HOCHMAN, JS RADOSLOVICH, G STEINBERG, JS ROTHBART, ST CASE, R DWYER, EM SQUATRITO, A KELLY, M CAMPION, JM TORMEY, D ANTHONY, R CALLAGHAN, E CHAPNICK, M RIPLEY, B FONTANA, C SCHLANT, RC ARENSBERG, D CORSO, JA HURST, JW MORRIS, DC SHERMAN, SW SILVERMAN, BD SILVERMAN, ME ROBERTS, JS BALLOU, SK JEFFRIES, VD BRACKNEY, BA SEALS, AA HARTLEY, J BAKER, RM GILMOUR, KE BAKER, SB HOWARD, J KATZ, RJ BESCH, GA BRILL, D DIBIANCO, R DONOHUE, D FISHER, G FRANCIS, C FRIEDMAN, D GOLDBERG, D GOLDBERG, S KOSS, G LARCA, L LEONARD, R LINDGREN, K RONAN, J ROSENBLATT, A ROSING, D ROSS, A ROTSZTAIN, A SHAWL, F SINDERSON, T STEVENSON, R TINKER, B VARGHESE, J YACKEE, J BIGHAM, H FRANKLIN, W GOLD, R GRAHAM, G GROSSBERG, D HOARE, R LEVY, W MAHMOOD, T TANNENBAUM, E TULLNER, W EISENHOWER, E GERACI, T WILHELMSEN, L BERGSTRAND, R FREDLUND, BO SIGURDSSON, A SIVERTSSON, R SWEDBERG, K HOULTZ, B WIKLUND, I SCHLYTER, G HEDELIN, G LEIJON, M MORGANROTH, J CARVER, J HOROWITZ, L KUTALEK, S PAPA, L SANDBERG, J VICTOR, M CESARE, S VRABEL, C TALARICO, K LUHMANN, S PALAZZO, D GOLDSTEIN, S GOLDBERG, AD FRUMIN, H WESTVEER, D DEBUTLIER, M SCHAIRER, J STOMEL, R FRANK, DM JARANDILLA, R DAVEY, D HASSE, C SHINNEY, S MORLEDGE, JH FARNHAM, DJ HINDERACKER, PH MUSSER, WE DEVRIES, K KUSHNER, JA RAO, R PETERSON, DT MCCAULEY, CS BERGEN, TS BOWMAN, KO GILLMAN, A FULLER, L OBRIEN, J MORLEDGE, J DEMARIA, AN KUO, CS KAMMERLING, JM CORUM, J THIEMANN, M SCHRODT, R PETERS, R SUTTON, F GOTTLIEB, S PAPUCHIS, G MATTIONI, T TODD, L CUSACK, C SCHECK, J HUANG, SKS ALPERT, JS GORE, JM RYAN, M COLLETTWILLEY, P CHAHINE, RA SEQUEIRA, RF LOWERY, MH DELGADO, LM CORREA, JL LASO, LJ HODGES, M SALERNO, D ANDERSON, B COLLINS, R DENES, P DUNBAR, D GRANRUD, G HAUGLAND, J HESSION, W MCBRIDE, J GORNICK, C SIMONSON, J TOLINS, M ETTINGER, A PETERSON, S SLIVKEN, R GRIMALDI, L ROY, D THEROUX, P LEMERY, R MORISSETTE, D BEAUDOIN, D GIRARD, L LAVALLEE, E MCANULTY, JH REINHART, SE MAURICE, G MURPHY, ES KRON, J MARCHANT, C BOXER, J PRINCEHOUSE, L SINNER, K BEANLANDS, D DAVIES, R GREEN, M WILLIAMS, W BAIRD, MJ GARRARD, L HEAL, S HASPECT, A BORTHWICK, J MAROIS, L WOODEND, K AKIYAMA, T HOOD, WB EASLEY, R RYAN, G KENIEN, G PATT, M KAZIERAD, D GOLDFARB, A BUTLER, LL KELLER, ML STANLEY, P PEEBLES, J SYROCKI, D LAVIN, D DENES, P SCHOENBERGER, JA LIEBSON, PR STAMATO, NJ PETROPULOS, AT BUCKINGHAM, TA REMIJAS, T KOCOUREK, J JANKO, K BARKER, AH ANDERSON, JL FOWLES, RE KEITH, TB WILLIAMS, CB MORENO, FL DORAN, EN FOWLER, B SUMMERS, K WHITE, C OHARA, G ROULEAU, JL PLANTE, S VINCENT, C BOUCHARD, D ZOBLE, RG OTERO, JE BUGNI, WJ SCHWARTZ, KM SHETTIGAR, UR BREWINGTON, JA UMBERGER, J COHEN, JD BJERREGAARD, P HAMILTON, WP GARNER, M ANDERSON, S ELSHERIF, N URSELL, SN GABOR, GE IBRAHIM, B ASSADI, M BREZSNYAK, ML PORTER, AV STANIORSKI, A WOOSLEY, RL RODEN, DM CAMPBELL, WB ECHT, DS LEE, JT MURRAY, KT SPELL, JD BONHOTAL, ST JARED, LL THOMAS, TI GOLDNER, F RICHARDSON, DW ROMHILT, DW ELLENBOGEN, KA BANE, BB FIELDS, J SHRADER, S POWELL, E CHAFFIN, CF WELLS, A CONWAY, KT PLATIA, EV ODONOGHUE, S TRACY, CM ALI, N BOWEN, P BROOKS, KM OETGEN, W WESTON, LT CARSON, P OBIASMANNO, D HARRISON, J SAYLOR, A POWELL, S HAAKENSON, CM SATHER, MR MALONE, LA HALLSTROM, AP MCBRIDE, R GREENE, HL BROOKS, MM LEDINGHAM, R REYNOLDSHAERTLE, RA HUTHER, M SCHOLZ, M MORRIS, M FRIEDMAN, LM SCHRON, E VERTER, J JENNINGS, C PROSCHAN, M BRISTOW, JD DEMETS, DL FISCH, C NIES, AS RUSKIN, J STRAUSS, H WALTERS, L TI EFFECT OF THE ANTIARRHYTHMIC AGENT MORICIZINE ON SURVIVAL AFTER MYOCARDIAL-INFARCTION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ARRHYTHMIA SUPPRESSION TRIAL; VENTRICULAR ARRHYTHMIAS; STIMULATION; MORTALITY AB Background. The Cardiac Arrhythmia Suppression Trial (CAST) tested the hypothesis that the suppression of asymptomatic or mildly symptomatic ventricular premature depolarizations in survivors of myocardial infarction would decrease the number of deaths from ventricular arrhythmias and improve overall survival. The second CAST study (CAST-II) tested this hypothesis with a comparison of moricizine and placebo. Methods. CAST-II was divided into two blinded, randomized phases: an early, 14-day exposure phase that evaluated the risk of starting treatment with moricizine after myocardial infarction (1325 patients), and a long-term phase that evaluated the effect of moricizine on survival after myocardial infarction in patients whose ventricular premature depolarizations were either adequately suppressed by moricizine (1155 patients) or only partially suppressed (219 patients). Results. CAST-II was stopped early because the first 14-day period of treatment with moricizine after a myocardial infarction was associated with excess mortality (17 of 665 patients died or had cardiac arrests), as compared with no treatment or placebo (3 of 660 patients died or had cardiac arrests); and estimates of conditional power indicated that it was highly unlikely (<8 percent chance) that a survival benefit from moricizine could be observed if the trial were completed. At the completion of the long-term phase, there were 49 deaths or cardiac arrests due to arrhythmias in patients assigned to moricizine, and 42 in patients assigned to placebo (adjusted P = 0.40). Conclusions. As with the antiarrhythmic agents used in CAST-I (flecainide and encainide), the use of moricizine in CAST-II to suppress asymptomatic or mildly symptomatic ventricular premature depolarizations to try to reduce mortality after myocardial infarction is not only ineffective but also harmful. C1 UNIV ALABAMA, BIRMINGHAM, AL 35294 USA. BAYLOR COLL MED, HOUSTON, TX 77030 USA. BROWN UNIV, CTR AFFILIATED HOSP, PROVIDENCE, RI 02912 USA. UNIV CALGARY, CALGARY T2N 1N4, ALBERTA, CANADA. UNIV CALIF IRVINE, IRVINE MED CTR, ORANGE, CA 92668 USA. UNIV CALIF SAN FRANCISCO, SAN FRANCISCO AFFILIATED HOSP, SAN FRANCISCO, CA 94143 USA. CASE WESTERN RESERVE UNIV, CLEVELAND, OH 44106 USA. UNIV MARYLAND, BALTIMORE, MD 21201 USA. UNIV MASSACHUSETTS, AMHERST, MA 01003 USA. UNIV MIAMI, CORAL GABLES, FL 33124 USA. UNIV MINNESOTA, MINNEAPOLIS, MN 55455 USA. MONTREAL HEART INST, MONTREAL H1T 1C8, QUEBEC, CANADA. OREGON HLTH SCI UNIV, PORTLAND, OR 97201 USA. UNIV OTTAWA, OTTAWA K1N 6N5, ONTARIO, CANADA. UNIV ROCHESTER, ROCHESTER, NY 14627 USA. RUSH PRESBYTERIAN ST LUKES MED CTR, CHICAGO, IL 60612 USA. SALT LAKE CLIN RES FDN, SALT LAKE CITY, UT USA. UNIV SHERBROOKE, CHU, SHERBROOKE J1K 2R1, QUEBEC, CANADA. UNIV S FLORIDA, TAMPA, FL 33620 USA. ST LOUIS UNIV, ST LOUIS, MO 63103 USA. SUNY HLTH SCI CTR BROOKLYN, BROOKLYN, NY USA. VANDERBILT UNIV, NASHVILLE, TN 37240 USA. VIRGINIA COMMONWEALTH UNIV, MED COLL VIRGINIA, RICHMOND, VA 23298 USA. WASHINGTON HOSP CTR, WASHINGTON, DC 20010 USA. UNIV WASHINGTON, CTR COORDINATING, SEATTLE, WA 98195 USA. NHLBI, DIV EPIDEMIOL & CLIN APPLICAT, CLIN TRIALS BRANCH, PROGRAM OFF, BETHESDA, MD 20892 USA. INDIANA UNIV, SCH MED, KRANNERT INST CARDIOL, INDIANAPOLIS, IN 46202 USA. COLUMBIA UNIV, AFFILIATED HOSP, NEW YORK, NY 10027 USA. EMORY UNIV, SCH MED, ATLANTA, GA 30322 USA. UNIV FLORIDA, JACKSONVILLE, FL USA. GEORGE WASHINGTON UNIV, MED CTR, WASHINGTON, DC 20037 USA. GOTHENBURG UNIV, S-41124 GOTHENBURG, SWEDEN. HAHNEMANN UNIV, PHILADELPHIA, PA 19102 USA. HENRY FORD HOSP, DETROIT, MI 48202 USA. JACKSON FDN MED EDUC & RES, MADISON, WI USA. UNIV KENTUCKY, LEXINGTON, KY 40506 USA. UNIV WISCONSIN, MADISON, WI 53706 USA. UNIV COLORADO, SCH MED, BOULDER, CO 80309 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. DUKE UNIV, MED CTR, DURHAM, NC 27710 USA. GEORGETOWN UNIV, KENNEDY INST ETH, WASHINGTON, DC 20057 USA. VET AFFAIRS MED CTR, COOPERAT STUDIES PROGRAM, CTR CLIN RES PHARM COORDINAT, CTR DRUG DISTRIBUT, ALBUQUERQUE, NM USA. RP ROGERS, WJ (reprint author), CARDIAC ARRHYTHMIA SUPRESS TRIAL, CTR COORDINATING CTR, 1107 NE 45TH ST, RM 505, SEATTLE, WA 98105 USA. NR 23 TC 595 Z9 605 U1 1 U2 9 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 23 PY 1992 VL 327 IS 4 BP 227 EP 233 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA JE381 UT WOS:A1992JE38100003 ER PT J AU BENYA, RV WANG, LH LIN, JT WADA, E BATTEY, JF JENSEN, RT AF BENYA, RV WANG, LH LIN, JT WADA, E BATTEY, JF JENSEN, RT TI NEUROMEDIN-B (NMB) RECEPTOR-PEPTIDE INTERACTION - BINDING, REGULATION AND CELL ACTIVATION SO REGULATORY PEPTIDES LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. 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 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD JUL 23 PY 1992 VL 40 IS 2 BP 111 EP 111 DI 10.1016/0167-0115(92)90139-L PG 1 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA JG987 UT WOS:A1992JG98700017 ER PT J AU DEWEERTH, A PISEGNA, JR WANK, SA AF DEWEERTH, A PISEGNA, JR WANK, SA TI THE CCKA RECEPTOR IN PANCREAS AND GALLBLADDER ARE IDENTICAL - MOLECULAR-CLONING AND FUNCTIONAL-STUDIES SO REGULATORY PEPTIDES LA English DT Meeting Abstract C1 NATL INST DIABETES DIGEST & KIDNEY,DIGEST DIS BRACH,BETHESDA,MD. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD JUL 23 PY 1992 VL 40 IS 2 BP 132 EP 132 PG 1 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA JG987 UT WOS:A1992JG98700059 ER PT J AU QIAN, JM JENSEN, RT AF QIAN, JM JENSEN, RT TI GASTRIN AND CHOLECYSTOKININ (CCK) ACTIVATE PHOSPHOLIPASE-C AND CAUSE PEPSINOGEN RELEASE IN GASTRIC CHIEF CELLS BY 2 DISTINCT RECEPTORS SO REGULATORY PEPTIDES LA English DT Meeting Abstract C1 NIH,DIGEST DIS BRANCH,BETHESDA,MD 20892. 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 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD JUL 23 PY 1992 VL 40 IS 2 BP 233 EP 233 DI 10.1016/0167-0115(92)90383-6 PG 1 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA JG987 UT WOS:A1992JG98700261 ER PT J AU WANG, TC BONNERWEIR, S OATES, PS CHULAK, M MERLINO, G SCHMIDT, EV BRAND, SJ AF WANG, TC BONNERWEIR, S OATES, PS CHULAK, M MERLINO, G SCHMIDT, EV BRAND, SJ TI GASTRIN PROMOTES ISLET CELL-GROWTH THROUGH INTERACTIONS WITH TRANSFORMING GROWTH FACTOR-ALPHA SO REGULATORY PEPTIDES LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02114. JOSLIN DIABET CTR,BOSTON,MA. NCI,BETHESDA,MD 20892. 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 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD JUL 23 PY 1992 VL 40 IS 2 BP 275 EP 275 PG 1 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA JG987 UT WOS:A1992JG98700344 ER PT J AU WANK, SA PISEGNA, JR DEWEERTH, A AF WANK, SA PISEGNA, JR DEWEERTH, A TI THE BRAIN AND GASTROINTESTINAL CHOLECYSTOKININ RECEPTOR FAMILY - STRUCTURE AND FUNCTIONAL EXPRESSION SO REGULATORY PEPTIDES LA English DT Meeting Abstract C1 NIDDK,DIGEST DIS BRANCH,BETHESDA,MD. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD JUL 23 PY 1992 VL 40 IS 2 BP 277 EP 277 DI 10.1016/0167-0115(92)90471-6 PG 1 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA JG987 UT WOS:A1992JG98700348 ER PT J AU MOFENSON, LM MOYE, J BETHEL, J HIRSCHHORN, R JORDAN, C NUGENT, R AF MOFENSON, LM MOYE, J BETHEL, J HIRSCHHORN, R JORDAN, C NUGENT, R TI PROPHYLACTIC INTRAVENOUS IMMUNOGLOBULIN IN HIV-INFECTED CHILDREN WITH CD4+ COUNTS OF 0.20X10(9)/L OR MORE - EFFECT ON VIRAL, OPPORTUNISTIC, AND BACTERIAL-INFECTIONS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNE-DEFICIENCY SYNDROME; VIRUS AB Objective.-To evaluate the efficacy of intravenous immunoglobulin (IVIG) for prevention of viral, opportunistic, and minor bacterial infections in children infected with human immunodeficiency virus (HIV). Design.-Randomized, double-blind, placebo-controlled, outpatient clinical trial comparing subjects treated with 400 mg of IVIG per kilogram of body weight every 28 days with those given albumin placebo. Setting.-Twenty-eight clinical centers in mainland United States and Puerto Rico. Patients.-Three hundred seventy-six children infected with human immunodeficiency virus with clinical or immunologic evidence of HIV disease, 313 of whom had entry CD4+ counts of at least 0.20 X 10(9)/L (greater-than-or-equal-to 200/mm3). Main Outcome Measures.-The incidence of laboratory-proven and clinically diagnosed viral, opportunistic, and bacterial infections. Main Results.-Viral infections and minor bacterial infections contributed more frequently to morbidity in children with entry CD4+ counts of at least 0.20 X 10(9)/L (together over five times as frequent) than did serious bacterial infection, the primary outcome measure of the trial. Opportunistic infections occurred at a similar rate as laboratory-proven serious bacterial infections. In this group of children, IVIG was significantly associated with a decrease in the rate of viral infections and minor bacterial infections per 100 patient-years (36.0 vs 54.0 episodes of viral infection per 100 patient-years, IVIG vs placebo, P=.01; and 115.1 vs 159.7 episodes of minor bacterial infection per 100 patient-years, IVIG vs placebo, P=.02), as well as a decrease in the rate of serious bacterial infections per 100 patient-years (26.4 vs 48.2 episodes per 100 patient-years; P=.002). There was no apparent difference in the rate of opportunistic infections between treatment arms. Conclusions.-Beneficial effect of IVIG was seen across multiple infectious outcome measures, with reductions in serious and minor viral and bacterial infections observed in children with entry CD4+ counts of at least 0.20 X 10(9)/L. C1 WESTAT CORP,ROCKVILLE,MD. RP MOFENSON, LM (reprint author), NICHHD,CTR RES MOTHERS & CHILDREN,6120 EXECUT BLVD,ROOM 450,BETHESDA,MD 20892, USA. NR 34 TC 80 Z9 80 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 JUL 22 PY 1992 VL 268 IS 4 BP 483 EP 488 DI 10.1001/jama.268.4.483 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA JD472 UT WOS:A1992JD47200022 PM 1352363 ER PT J AU ROSENBERG, PS LEVY, ME BRUNDAGE, JF PETERSEN, LR KARON, JM FEARS, TR GARDNER, LI GAIL, MH GOEDERT, JJ BLATTNER, WA RYAN, CC VERMUND, SH BIGGAR, RJ AF ROSENBERG, PS LEVY, ME BRUNDAGE, JF PETERSEN, LR KARON, JM FEARS, TR GARDNER, LI GAIL, MH GOEDERT, JJ BLATTNER, WA RYAN, CC VERMUND, SH BIGGAR, RJ TI POPULATION-BASED MONITORING OF AN URBAN HIV AIDS EPIDEMIC - MAGNITUDE AND TRENDS IN THE DISTRICT-OF-COLUMBIA SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SHORT-TERM PROJECTIONS; UNITED-STATES; SENTINEL HOSPITALS; INFECTION; PREVALENCE; SPREAD; SIZE AB Objective.-To assess the extent of the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemic in the District of Columbia and demonstrate an approach to monitoring HIV infection and projecting AIDS incidence at a community level. Design.-Backcalculation methods to reconstruct HIV incidence from AIDS incidence in subgroups. Results were compared with directly measured HIV seroprevalence in selected sentinel populations: childbearing women, civilian applicants for military service, and hospital patients admitted for conditions unrelated to HIV infection. Results.-Between the start of the epidemic in 1980 and January 1, 1991, one in 57 District of Columbia men aged 20 to 64 years was diagnosed with AIDS. Unlike the plateau projected for the nation, AIDS incidence for the District of Columbia was projected to increase by 34% between 1990 and 1994. Models of HIV infection incidence suggested two broad epidemic waves of approximately equal size. The first occurred in men who have sex with men and peaked during the period from 1982 through 1983. The second began in the mid-1980s in injecting drug users and heterosexuals. We estimated that among District of Columbia residents aged 20 to 64 years, 0.3% of white women, 2.9% of white men, 1.6% of black women, and 4.9% of black men were living with HIV infection as of January 1, 1991. These estimates are broadly consistent with survey data: among black childbearing women in their 20s, HIV prevalence doubled to 2% between the fall of 1989 and the spring of 1991; from military applicant data, we estimated that over 5% of black men born from 1951 through 1967 were HIV-positive; in the sentinel hospital, HIV prevalence rates among male patients aged 25 to 34 years were 11.3% in white men and 16.9% in black men. Conclusion.-Backcalculation and surveys yielded quantitatively consistent estimates of HIV prevalence. Many injecting drug users and heterosexuals in the District of Columbia were infected after January 1, 1986. Similar monitoring of the epidemic in other localities is needed to focus efforts to reduce the incidence of HIV transmission. C1 NCI,ENVIRONM EPIDEMIOL BRANCH,VIRAL EPIDEMIOL SECT,ROCKVILLE,MD 20892. WALTER REED ARMY MED CTR,DIV PREVENT MED,WASHINGTON,DC 20307. CTR DIS CONTROL,CTR INFECT DIS,DIV HIV AIDS,POPULAT STUDIES SECT,ATLANTA,GA 30333. CTR DIS CONTROL,CTR INFECT DIS,DIV HIV AIDS,STAT & DATA MANAGEMENT BRANCH,ATLANTA,GA 30333. DIST COLUMBIA COMMISS PUBL HLTH,AGCY HIV AIDS,WASHINGTON,DC. NIAID,DIV AIDS,VACCINE TRIALS EPIDEMIOL BRANCH,BETHESDA,MD 20892. DIST COLUMBIA COMMISS PUBL HLTH,PREVENT HLTH SERV ADM,WASHINGTON,DC. RP ROSENBERG, PS (reprint author), NCI,BIOSTAT BRANCH,EPIDEMIOL METHODS SECT,6130 EXECUT BLVD,EPN 403,ROCKVILLE,MD 20892, USA. OI Vermund, Sten/0000-0001-7289-8698 NR 45 TC 24 Z9 24 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 JUL 22 PY 1992 VL 268 IS 4 BP 495 EP 503 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA JD472 UT WOS:A1992JD47200024 PM 1619741 ER PT J AU BATES, SE CURRIER, SJ ALVAREZ, M FOJO, AT AF BATES, SE CURRIER, SJ ALVAREZ, M FOJO, AT TI MODULATION OF P-GLYCOPROTEIN PHOSPHORYLATION AND DRUG TRANSPORT BY SODIUM-BUTYRATE SO BIOCHEMISTRY LA English DT Article ID MULTIDRUG-RESISTANCE GENE; INDUCED DIFFERENTIATION; CROSS-RESISTANCE; CARCINOMA-CELLS; PROTEIN-KINASE; PHORBOL ESTERS; EXPRESSION; PROGESTERONE; LINES AB P-Glycoprotein (Pgp) expression in cell lines derived from tumors arising from cells which normally express Pgp can be increased by sodium butyrate and other differentiating agents. Although the Pgp level increased 25-fold after sodium butyrate treatment in SW620 human colon carcinoma cells, the intracellular accumulation of vinblastine, adriamycin, and actinomycin D increased rather than decreased. In contrast, colchicine showed the expected decrease in accumulation, as a result of increased efflux. Likewise, treatment of a Pgp-expressing multidrug-resistant SW620 subline with sodium butyrate resulted in active interference with Pgp function. This effect was partially reversed by phorbol esters with a resulting decrease in the accumulation of vinblastine, adriamycin, and actinomycin D. Sodium butyrate, while increasing Pgp levels, inhibited the phosphorylation of Pgp. Time course studies revealed a tight relationship between decreased Pgp phosphorylation and increased vinblastine accumulation after sodium butyrate treatment. Either treatment with phorbol esters or withdrawal of sodium butyrate increased Pgp phosphorylation while decreasing vinblastine accumulation. These studies suggest that the specificity of Pgp transport can be modulated by phosphorylation and that vinblastine, adriamycin, or actinomycin D transport, but not that of colchicine, is diminished after dephosphorylation by sodium butyrate. C1 NCI,DIV CANC BIOL DIAG & CTR,CELL BIOL LAB,BETHESDA,MD 20892. RP BATES, SE (reprint author), NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,MED BRANCH,BETHESDA,MD 20892, USA. NR 24 TC 83 Z9 85 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 JUL 21 PY 1992 VL 31 IS 28 BP 6366 EP 6372 DI 10.1021/bi00143a002 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JE536 UT WOS:A1992JE53600002 PM 1352990 ER PT J AU CASASFINET, JR HU, S HAMER, D KARPEL, RL AF CASASFINET, JR HU, S HAMER, D KARPEL, RL TI CHARACTERIZATION OF THE COPPER-THIOLATE AND SILVER-THIOLATE CLUSTERS IN N-TERMINAL FRAGMENTS OF THE YEAST ACE1 TRANSCRIPTION FACTOR CAPABLE OF BINDING TO ITS SPECIFIC DNA RECOGNITION SEQUENCE SO BIOCHEMISTRY LA English DT Article ID METALLOTHIONEIN GENE-TRANSCRIPTION; PROTEIN; ABSORPTION; PLASTOCYANIN; CONFORMATION; CRYSTAL; IONS; CU+ AB N-terminal fragments of ACE1 protein spanning residues 1-122 or 1-110, termed ACE1(122*) and ACE1(110*), respectively, were investigated in regard to their metal- and double-stranded DNA-binding properties. Band mobility shift assays showed that binding to a specific oligonucleotide (termed UASc), containing two ACE1(122*) binding sites, requires the presence of Cu(I) or Ag(I) but does not occur in the presence of divalent metal ions. Both the Ag(I) and the Cu(I) forms of ACE1(122*) were characterized spectroscopically. The Tyr and metal cluster luminescence emission of Cu-ACE1(122*) was specifically quenched by the oligonucleotide UAScL, but not by an oligonucleotide of the same length and base composition but scrambled sequence. The room-temperature luminescence of Cu(I)-ACE1(122*) was assigned to a phosphorescence emission, on the basis of its long-lived luminescence of approximately 3.5-mu-s. We report the first observation of a Ag(I) metal cluster in solution for Ag(I)-ACE1(122*), which was found to exhibit a quantum yield and average luminescence lifetime that are ca. 6% of that of Cu(I)-ACE1(122*). The three-dimensional structure brought about by the binding of either metal ion appears to be very similar, since dynamic tyrosine fluorescence lifetime measurements, as well as circular dichroism spectra, were nearly identical for Cu- and Ag-ACE1(122*). Based on these results, we present a hypothetical model for the structure of the metal cluster in this class of proteins. C1 UNIV MARYLAND,DEPT CHEM & BIOCHEM,CATONSVILLE,MD 21228. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 38 TC 32 Z9 32 U1 2 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 21 PY 1992 VL 31 IS 28 BP 6617 EP 6626 DI 10.1021/bi00143a036 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JE536 UT WOS:A1992JE53600036 PM 1633174 ER PT J AU ROSTENE, W BOJA, JW SCHERMAN, D CARROLL, FI KUHAR, MJ AF ROSTENE, W BOJA, JW SCHERMAN, D CARROLL, FI KUHAR, MJ TI DOPAMINE TRANSPORT - PHARMACOLOGICAL DISTINCTION BETWEEN THE SYNAPTIC MEMBRANE AND THE VESICULAR TRANSPORTER IN RAT STRIATUM SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Note DE DOPAMINE; DOPAMINE TRANSPORTERS; SYNAPTIC VESICLE; AMINE UPTAKE ID COCAINE RECEPTORS; CATECHOLAMINE AB The pharmacological properties of the monoamine transporters in the synaptic vesicles and of the dopamine transporters in the synaptic plasma membrane were compared. Tetrabenazine, an inhibitor of the vesicular transporter did not block ligand binding to the plasma membrane transporter. Various potent cocaine analogues and other compounds active at the plasma membrane transporter did not block ligand binding to the vesicular transporter. These data indicate pharmacological differences between the vesicular and synaptic membrane transporters. C1 NIDA,NEUROSCI BRANCH,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224. HOP ST ANTOINE,INSERM,U339,F-75571 PARIS 12,FRANCE. CNRS,RHONE POULENC RORER,F-94400 VITRY,FRANCE. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. RI Rostene, William/F-2754-2017 NR 11 TC 15 Z9 15 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 JUL 21 PY 1992 VL 218 IS 1 BP 175 EP 177 DI 10.1016/0014-2999(92)90162-W PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JG590 UT WOS:A1992JG59000023 PM 1397029 ER PT J AU HIRSCH, J PETRAKOVA, E FEATHER, MS AF HIRSCH, J PETRAKOVA, E FEATHER, MS TI THE REACTION OF SOME DICARBONYL SUGARS WITH AMINOGUANIDINE SO CARBOHYDRATE RESEARCH LA English DT Article ID CROSS-LINKING; MAILLARD REACTION; ASCORBIC-ACID; LENS PROTEINS; 3-DEOXYGLUCOSONE; GLUCOSE; GLYCOSYLATION AB The reactions of aminoguanidine (guanylhydrazine) with 3-deoxy-D-erythro-hexos-2-ulose (1a), 3-deoxy-D-glycero-pentose-2-ulose (1b), D-erythro-hexos-2-ulose (1c), and D-glycero-pentose-2-ulose (1d) were examined at 37-degrees at a solution pH of 7.0 (phosphate buffer). For 1a and 1b, two major products were observed and shown respectively to be the 5- and 6-substituted 3-amino-1,2,4-triazine derivatives. The ratios of the products were independent of the amount of aminoguanidine present or the order of mixing the reagents prior to the experiments. For 1c and 1d, only the 5-substituted triazine derivatives were formed, No evidence for hydrazone or bishydrazone formation was observed. C1 UNIV MISSOURI,DEPT BIOCHEM,COLUMBIA,MO 65211. NIDDK,BETHESDA,MD 20892. NR 20 TC 59 Z9 60 U1 3 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD JUL 20 PY 1992 VL 232 IS 1 BP 125 EP 130 DI 10.1016/S0008-6215(00)90999-6 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA JJ988 UT WOS:A1992JJ98800010 PM 1423344 ER PT J AU FARBER, R LAPEDES, A SIROTKIN, K AF FARBER, R LAPEDES, A SIROTKIN, K TI DETERMINATION OF EUKARYOTIC PROTEIN CODING REGIONS USING NEURAL NETWORKS AND INFORMATION-THEORY SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE CODING REGION; NEURAL NETS; INFORMATION THEORY; EXON; INTRON ID NUCLEIC-ACID SEQUENCES; DNA-SEQUENCES; CODON PREFERENCE C1 NIH,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20892. RP FARBER, R (reprint author), LOS ALAMOS NATL LAB,DIV THEORET,LOS ALAMOS,NM 87545, USA. FU NIGMS NIH HHS [GM 40789-03] NR 14 TC 70 Z9 74 U1 0 U2 3 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 JUL 20 PY 1992 VL 226 IS 2 BP 471 EP 479 DI 10.1016/0022-2836(92)90961-I PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JF966 UT WOS:A1992JF96600017 PM 1640461 ER PT J AU MCCANN, DJ SU, TP AF MCCANN, DJ SU, TP TI TRIS INHIBITS (+)-[3H]SKF-10,047 BINDING TO SIGMA-RECEPTORS SO NEUROSCIENCE LETTERS LA English DT Article DE BUFFER; HALOPERIDOL; SIGMA-RECEPTOR; (+)-SKF-10,047; TRIS ID RAT-BRAIN MEMBRANES; SITES; PHENCYCLIDINE; (+)-SKF-10,047; AFFINITY; STATES; LIGAND AB Tris-HCl is the most commonly used buffer in studies of radioligand binding to sigma-receptors, with concentrations as high as 50 or 100 mM often used. We report here that these concentrations of Tris substantially inhibit (+)-[H-3]SKF-10,047 binding to sigma-receptors. The well-established inhibitory effect of Tris-HCl on ligand binding to PCP receptors did not contribute to the presently reported inhibition of (+)-[H-3]SKF-10,047 binding. The IC50 of Tris, determined in the presence of 10 mM potassium phosphate buffer, was 15.4+/-1.2 mM (n=3, pH 8.0, 25-degrees-C, 1 nM radioligand). Equilibrium saturation studies revealed an apparent competitive inhibition of binding. RP MCCANN, DJ (reprint author), NIDA,ADDICT RES CTR,NEUROPHARMACOL LAB,NEUROCHEM UNIT,POB 5180,BALTIMORE,MD 21224, USA. NR 17 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUL 20 PY 1992 VL 141 IS 2 BP 239 EP 242 DI 10.1016/0304-3940(92)90903-K PG 4 WC Neurosciences SC Neurosciences & Neurology GA JH045 UT WOS:A1992JH04500026 PM 1436640 ER PT J AU SWAIN, MG HEYES, MP VERGALLA, J JONES, EA AF SWAIN, MG HEYES, MP VERGALLA, J JONES, EA TI METHIONINE ENKEPHALIN ACCUMULATES IN PLASMA BUT NOT IN BRAIN OR CEREBROSPINAL-FLUID OF RATS WITH ACUTE TOXIC HEPATITIS SO NEUROSCIENCE LETTERS LA English DT Article DE METHIONINE ENKEPHALIN; TOXIC HEPATITIS; BLOOD-TO-BRAIN TRANSFER ID RABBIT MODEL; LEUCINE-ENKEPHALIN; OPIOID-PEPTIDES; ENCEPHALOPATHY; BARRIER; TRANSPORT; ACID AB In order to determine whether acute toxic hepatitis in the rat is associated with an accumulation of methionine enkephalin in plasma and increased blood-to-brain transfer of methionine enkephalin, immunoreactive methionine enkephalin levels were determined by radioimmunoassay in plasma, cerebrospinal fluid and whole brain samples from rats with thioacetamide induced acute toxic hepatitis. Thioacetamide treatment was associated with an 8.7-fold increase in plasma immunoreactive methionine enkephalin levels (P less-than-or-equal-to 0.005) 24 h after treatment. However, this marked elevation in plasma immunoreactive methionine enkephalin levels was not associated with an increase in whole brain or cerebrospinal fluid immunoreactive methionine enkephalin levels. These data suggest that increased plasma-to-brain transfer of methionine enkephalin does not occur in this model of acute toxic hepatitis. C1 NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BETHESDA,MD 20892. RP SWAIN, MG (reprint author), NIDDK,LIVER DIS SECT,BLDG 10,RM 4D-52,BETHESDA,MD 20892, USA. NR 20 TC 5 Z9 5 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 JUL 20 PY 1992 VL 141 IS 2 BP 243 EP 246 DI 10.1016/0304-3940(92)90904-L PG 4 WC Neurosciences SC Neurosciences & Neurology GA JH045 UT WOS:A1992JH04500027 PM 1436641 ER PT J AU CRAWLEY, JN EVERS, JR PAUL, SM AF CRAWLEY, JN EVERS, JR PAUL, SM TI POLYAMINES INHIBIT N-METHYL-D-ASPARTATE ANTAGONIST-INDUCED DARTING BEHAVIOR IN THE RAT PREFRONTAL CORTEX SO BRAIN RESEARCH LA English DT Article DE POLYAMINE; NMDA RECEPTOR; PREFRONTAL CORTEX; ALLOSTERIC NEUROMODULATOR; DARTING BEHAVIOR; HYPERLOCOMOTION ID NMDA RECEPTOR COMPLEX; NUCLEUS-ACCUMBENS; RECOGNITION SITE; H-3 MK-801; IFENPRODIL; GLUTAMATE; BINDING; MODULATE; GLYCINE; SCHIZOPHRENIA AB The competitive NMDA (N-methyl-D-aspartate) receptor antagonist, CPP (3(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid), microinjected into the medial prefrontal cortex of rats, induces a unique behavioral syndrome termed 'darting', characterized by rapid leaping across an open field arena15. In addition, CPP induces generalized hyperactivity when microinjected into the medial prefrontal cortex, nucleus accumbens, and caudate nucleus. Polyamine modulation of the NMDA receptor was tested at the medial prefrontal cortex microinjection site in this bebavioral paradigm. The polyamine spermidine, and its diamine precursor, putrescine, blocked CPP-induced darting behavior, as well as CPP-induced hyperactivity, at doses which did not decrease locomotor activity when administered alone. The putative polyamine antagonists, ifenprodil and diethylenetriamine, did not prevent spermidine from inhibiting CPP-induced darting. These results suggest that polyamines, presumably by acting as positive allosteric modulators of the NMDA receptor, can inhibit the CPP-induced behavioral syndrome at the prefrontal cortex site. C1 NIMH,CLIN NEUROSCI BRANCH,MOLEC PHARMACOL SECT,BETHESDA,MD 20892. RP CRAWLEY, JN (reprint author), NIMH,EXPTL THERAPEUT BRANCH,BEHAV NEUROPHARMACOL UNIT,BLDG 10,ROOM 4N214,BETHESDA,MD 20892, USA. NR 31 TC 9 Z9 9 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 17 PY 1992 VL 586 IS 1 BP 6 EP 11 DI 10.1016/0006-8993(92)91364-K PG 6 WC Neurosciences SC Neurosciences & Neurology GA JH131 UT WOS:A1992JH13100002 PM 1511351 ER PT J AU WHITE, G LI, CY ISHAC, E AF WHITE, G LI, CY ISHAC, E TI 1,9-DIDEOXYFORSKOLIN DOES NOT MIMIC ALL CAMP AND PROTEIN KINASE-A INDEPENDENT EFFECTS OF FORSKOLIN ON GABA ACTIVATED ION CURRENTS IN ADULT-RAT SENSORY NEURONS SO BRAIN RESEARCH LA English DT Note DE INHIBITION; KINASE; NEUROTRANSMITTER; ION CHANNEL ID RECEPTOR DESENSITIZATION AB The effect of forskolin on GABA(A) receptor activated events has been the subject of recent investigations, the conclusions of which are conflicting. Forskolin can reduce current amplitude and increase the rate of decay of current activated by 100-mu-M GABA and these effects are not mimicked by 1,9-dideoxyforskolin (Tehrani et al., Synapse, 4 (1989) 126-131). On the other hand, both forskolin and 1,9-dideoxyforskolin inhibit Cl-36- flux induced by lower concentrations of muscimol (Heuschneider and Schwartz, Proc. Natl. Acad. Sci. USA, 86 (1989) 2938-2942). Using the whole-cell patch clamp technique to measure GABA activated current in dorsal root ganglion neurons that were freshly isolated from adult rats, we have confirmed the finding of Tehrani et al. (Synapse, 4 (1989) 126-131) using 100-mu-M. GABA; however, the effects of forskolin that were not mimicked by 1,9-dideoxyforskolin were not blocked by the kinase inhibitor H-7 (50-mu-M). In contrast, at lower concentrations of GABA (10-20-mu-M), both forskolin and 1,9-dideoxyforskolin increased the decay rate of GABA activated current, In addition, all effects of forskolin occurred within 200 ms of application of forskolin and the effects were not blocked or occluded by H-7, 10-mu-M cAMP, or the active subunit of protein kinase A. We conclude that: (1) 1,9-dideoxyforskolin is not a reliable indicator of forskolin specificity in this system because its effects are dependent upon GABA concentration; and (2) the most prominent effects of forskolin on amplitude and decay time course of GABA activated ion current are not mediated by cAMP or protein kinase A (PKA). C1 NIAAA,ELECTROPHYSIOL SECT,ROCKVILLE,MD 20852. NR 13 TC 14 Z9 14 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 JUL 17 PY 1992 VL 586 IS 1 BP 157 EP 161 DI 10.1016/0006-8993(92)91388-U PG 5 WC Neurosciences SC Neurosciences & Neurology GA JH131 UT WOS:A1992JH13100026 PM 1380877 ER PT J AU JUCKER, M BIALOBOK, P HAGG, T INGRAM, DK AF JUCKER, M BIALOBOK, P HAGG, T INGRAM, DK TI LAMININ IMMUNOHISTOCHEMISTRY IN BRAIN IS DEPENDENT ON METHOD OF TISSUE FIXATION SO BRAIN RESEARCH LA English DT Note DE BASEMENT MEMBRANE; NEOVASCULARIZATION; INTRANEURONAL LAMININ; ISCHEMIA; LESION; FORMALDEHYDE; CAPILLARIES; CENTRAL NERVOUS SYSTEM (CNS) ID BASEMENT-MEMBRANE GLYCOPROTEIN; CENTRAL NERVOUS-SYSTEM; ADULT; IMMUNOREACTIVITY; ANTIBODIES; PROTEIN; INJURY; ACID AB Normal adult and lesioned rat and mouse brains were fixed by formaldehyde perfusion by two methods that differ primarily in the length of the post-fixation period. Sections were subsequently immunostained using monoclonal and polyclonal antibodies to laminin. With relatively short post-fixation periods (up to 4 h), vascular basement membrane (BM)-laminin was immunostained, but intraneuronal laminin-like immunoreactivity was faint. With longer post-fixation periods (18-24 h), intraneuronal laminin-like immunoreactivity was distinct, while vascular BM-laminin immunoreactivity was reduced drastically. These findings are particularly relevant to studies examining laminin immunoreactive blood vessels in response to lesions, especially ischemic stroke. In fact, the present results suggest that the apparent neovascularization or up-regulation of vascular BM-laminin following CNS injury likely relates to differences in regional tissue fixation. C1 FISONS CORP,CNS RES LAB,ROCHESTER,NY 14624. UNIV CALIF SAN DIEGO,DEPT BIOL 0601,LA JOLLA,CA 92093. RP JUCKER, M (reprint author), NIA,GERONTOL RES CTR,CELLULAR & MOLEC BIOL LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 20 TC 40 Z9 40 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 JUL 17 PY 1992 VL 586 IS 1 BP 166 EP 170 DI 10.1016/0006-8993(92)91390-Z PG 5 WC Neurosciences SC Neurosciences & Neurology GA JH131 UT WOS:A1992JH13100028 PM 1380879 ER PT J AU HEALY, B AF HEALY, B TI IS THIS YOUR FATHERS NIH - AND OTHER STRATEGIC QUESTIONS SO SCIENCE LA English DT Article RP HEALY, B (reprint author), NIH,BETHESDA,MD 20892, USA. NR 7 TC 9 Z9 9 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 JUL 17 PY 1992 VL 257 IS 5068 BP 312 EP & DI 10.1126/science.1631548 PG 0 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JD674 UT WOS:A1992JD67400006 PM 1631548 ER PT J AU DAOPIN, S PIEZ, KA OGAWA, Y DAVIES, DR AF DAOPIN, S PIEZ, KA OGAWA, Y DAVIES, DR TI CRYSTAL-STRUCTURE OF TRANSFORMING GROWTH-FACTOR-BETA-2 - AN UNUSUAL FOLD FOR THE SUPERFAMILY SO SCIENCE LA English DT Article ID DEOXYRIBONUCLEIC-ACID CLONING; MESSENGER RIBONUCLEIC-ACID; X-RAY-DIFFRACTION; FACTOR-BETA; EMBRYO CHONDROCYTES; IDENTIFICATION; PURIFICATION AB The transforming growth factors-beta (TGF-beta-1 through -beta-5) are a family of homodimeric cytokines that regulate proliferation and function in many cell types. Family members have 66 to 80% sequence identity and nine strictly conserved cysteines. A crystal structure of a member of this family, TGF-beta-2, has been determined at 2.1 angstrom (angstrom) resolution and refined to an R factor of 0.172. The monomer lacks a well-defined hydrophobic core and displays an unusual elongated nonglobular fold with dimensions of approximately 60 angstrom by 20 angstrom by 15 angstrom. Eight cysteines form four intrachain disulfide bonds, which are clustered in a core region forming a network complementary to the network of hydrogen bonds. The dimer is stabilized by the ninth cysteine, which forms an interchain disulfide bond, and by two identical hydrophobic interfaces. Sequence profile analysis of other members of the TGF-beta superfamily, including the activins, inhibins, and several developmental factors, imply that they also adopt the TGF-beta fold. C1 NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. NIH,FOGARTY INT CTR,BETHESDA,MD 20892. CELTRIX PHARMACEUT INC,SANTA CLARA,CA 95052. NR 40 TC 361 Z9 373 U1 0 U2 6 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 17 PY 1992 VL 257 IS 5068 BP 369 EP 373 DI 10.1126/science.1631557 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JD674 UT WOS:A1992JD67400028 PM 1631557 ER PT J AU BODENTEICH, M MARQUEZ, VE AF BODENTEICH, M MARQUEZ, VE TI SYNTHESIS OF PROTECTED (+/-)-ALPHA-CARBA-PSICOFURANOSE AND BETA-CARBA-PSICOFURANOSE SO TETRAHEDRON LA English DT Article DE CARBA-PSICOFURANOSE; CARBOCYCLIC SUGAR; CARBOCYCLIC NUCLEOSIDE ANALOGS ID CARBOCYCLIC ANALOGS; D-FRUCTOFURANOSE; DERIVATIVES; TRANSFORMATION; PENTOFURANOSE AB Protected racemic alpha- and B-psicofuranose were synthesized from a non-carbohydrate precursor which is available in both enantiomeric forms. C1 NCI,DCT,DTP,MEDICINAL CHEM LAB,BETHESDA,MD 20892. NR 16 TC 2 Z9 2 U1 0 U2 0 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 JUL 17 PY 1992 VL 48 IS 29 BP 5961 EP 5968 DI 10.1016/S0040-4020(01)89845-8 PG 8 WC Chemistry, Organic SC Chemistry GA JF278 UT WOS:A1992JF27800003 ER PT J AU NAVASCASTILLO, J LAIGRET, F TULLY, JG BOVE, JM AF NAVASCASTILLO, J LAIGRET, F TULLY, JG BOVE, JM TI THE MOLLICUTE ACHOLEPLASMA-FLORUM POSSESSES A GENE OF THE PHOSPHOENOLPYRUVATE-SUGAR PHOSPHOTRANSFERASE SYSTEM AND UTILIZES UGA AS A TRYPTOPHAN CODON SO COMPTES RENDUS DE L ACADEMIE DES SCIENCES SERIE III-SCIENCES DE LA VIE-LIFE SCIENCES LA French DT Article ID METABOLISM; SEQUENCE; DNA AB Acholeplasmas are mollicutes which do not require sterol for growth and not possess a phosphoenolpyruvate-dependant sugar-phosphotransferase system. In contrast to spiroplasmas, mycoplasmas and ureaplasmas, they utilize UGA as a stop codon and not as a tryptophan codon. Acholeplasma florum, because of its metabolic properties and its close phylogenetic relationship to members of the genera Spiroplasma and Mycoplasma, does not seem to be an acholeplasma senso stricto. Here, we present molecular data to support this hypothesis. We have detected a gene coding for one of the components of the phosphotransferase system (PTS) in A. florum. In addition we demonstrate that the organism uses UGA as a tryptophan codon and not as a stop codon. These findings offer strong evidence, along with an earlier phylogenetic proposal, that A. florum is not a member of the genus Acholeplasma. C1 NIAID,MOLEC MICROBIOL LAB,FREDERICK CANC RES FACIL,FREDERICK,MD 21701. RP NAVASCASTILLO, J (reprint author), INRA,BIOL CELLULAIRE & MOLEC LAB,F-33883 VILLENAVE DORNON,FRANCE. RI Navas-Castillo, Jesus/G-3894-2011 OI Navas-Castillo, Jesus/0000-0002-8616-6241 NR 19 TC 10 Z9 10 U1 0 U2 1 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 0764-4469 J9 CR ACAD SCI III-VIE JI Comptes Rendus Acad. Sci. Ser. III-Sci. Vie-Life Sci. PD JUL 16 PY 1992 VL 315 IS 2 BP 43 EP 48 PG 6 WC Biology; Multidisciplinary Sciences SC Life Sciences & Biomedicine - Other Topics; Science & Technology - Other Topics GA JG207 UT WOS:A1992JG20700002 PM 1422919 ER PT J AU KATZ, SI AF KATZ, SI TI INHERITED AND ACQUIRED BLISTERING DISEASES SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID EPIDERMOLYSIS BULLOSA RP KATZ, SI (reprint author), NCI,BETHESDA,MD 20892, USA. NR 10 TC 3 Z9 3 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 JUL 16 PY 1992 VL 327 IS 3 BP 196 EP 197 DI 10.1056/NEJM199207163270312 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA JD319 UT WOS:A1992JD31900012 PM 1608411 ER PT J AU SUPERKO, HR GREENLAND, P MANCHESTER, RA ANDREADIS, NA SCHECTMAN, G WEST, NH HUNNINGHAKE, D HASKELL, WL PROBSTFIELD, JL AF SUPERKO, HR GREENLAND, P MANCHESTER, RA ANDREADIS, NA SCHECTMAN, G WEST, NH HUNNINGHAKE, D HASKELL, WL PROBSTFIELD, JL TI EFFECTIVENESS OF LOW-DOSE COLESTIPOL THERAPY IN PATIENTS WITH MODERATE HYPERCHOLESTEROLEMIA SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LOW-DENSITY; CORONARY ATHEROSCLEROSIS; II HYPERLIPOPROTEINEMIA; LIPOPROTEIN COMPOSITION; APOLIPOPROTEIN-B; CHOLESTYRAMINE; SEQUESTRANT; CHOLESTEROL; REGRESSION; DISEASE AB Recommended doses of bile-acid binding resins have an established hypocholesterolemic effect, but data on responses to low doses, especially in women and subjects with moderate hypercholesterolemia, are sparse. A double-blind, placebo-controlled, randomized trial of 3 low doses of colestipol hydrochloride was conducted in women and men with moderate hypercholesterolemia. Men and women with plasma low-density lipoprotein (LDL) cholesterol concentrations >4 mmol/liter (155 mg/dl) and triglyceride concentrations <2.82 mmol/liter (250 mg/dl) were recruited for the study. Eligible patients (54 women and 98 men) were placed on the American Heart Association step I diet 6 weeks before randomization. Participants were subsequently assigned to 1 of 4 drug treatment groups (placebo, and 5, 10 and 15 g/day of colestipol in 2 divided doses) for an additional 12 weeks. Of the 152 patients randomized, 141 completed all aspects of the study. For the treatment groups - placebo, and 5, 10 and 15 g of colestipol - LDL cholesterol reductions (mmol/liter) were observed respectively (n = 141): 0.10 +/- 0.49 (2.7%), 0.65 +/- 0.41 (16.3%), 0.98 +/- 0.36 (22.8%) and 1.17 +/- 0.47 (27.2%) (p <0.001). Similar changes were observed in total cholesterol and apolipoprotein B concentrations. The apolipoprotein B/LDL cholesterol ratio increased significantly with increasing colestipol dosage. Modest but insignificant changes in plasma triglyceride levels occurred, and high-density lipoprotein cholesterol levels remained unchanged. A dose of 5 g/day of colestipol achieved 51% of the LDL cholesterol reduction noted with 15 g/day. Low-dose colestipol therapy is effective in the treatment of patients with moderate hypercholesterolemia. The proportionally greater LDL cholesterol reduction in moderate compared with severe hypercholesterolemia was confirmed by examination of the Lipid Research Clinics' Coronary Primary Prevention Trial data set. C1 LAWRENCE BERKELEY LAB,CHOLESTEROL RES CTR,BERKELEY,CA 94720. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL 60611. UNIV ROCHESTER,MED CTR,GEN MED UNIT,ROCHESTER,NY 14642. MED COLL WISCONSIN,DIV FISIOL VEGETAL,MILWAUKEE,WI 53226. UPJOHN CO,KALAMAZOO,MI 49001. NIH,CLIN TRIALS BRANCH,BETHESDA,MD 20892. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. OI Superko, H. Robert/0000-0002-3542-0393 NR 25 TC 37 Z9 38 U1 0 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 JUL 15 PY 1992 VL 70 IS 2 BP 135 EP 140 DI 10.1016/0002-9149(92)91264-5 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JD355 UT WOS:A1992JD35500001 PM 1626496 ER PT J AU SCHERWITZ, LW PERKINS, LL CHESNEY, MA HUGHES, GH SIDNEY, S MANOLIO, TA AF SCHERWITZ, LW PERKINS, LL CHESNEY, MA HUGHES, GH SIDNEY, S MANOLIO, TA TI HOSTILITY AND HEALTH BEHAVIORS IN YOUNG-ADULTS - THE CARDIA STUDY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE ALCOHOL DRINKING; BODY MASS INDEX; CORONARY DISEASE; EXERCISE; HEALTH BEHAVIOR; HOSTILITY; MORTALITY; SMOKING ID CORONARY HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; FOLLOW-UP; CARDIOVASCULAR-DISEASE; TOTAL MORTALITY; MEN BORN; CYNICAL HOSTILITY; BLOOD-PRESSURE; ADIPOSE-TISSUE; CHD INCIDENCE AB Hostility has been associated with coronary heart disease mortality. To assess possible mechanisms linking hostility to coronary heart disease risk, the authors conducted analyses in a cross-sectional study from data collected in 1985 and 1986 on 5,115 young adults, aged 18-30 years, black and white, male and female, in four large urban areas of the United States. The results show that higher levels of hostility as determined by the Cook-Medley Hostility Scale were strongly associated with tobacco and marijuana smoking, increased alcohol consumption, and greater caloric intake in both blacks and whites and in both men and women. The increased caloric consumption was evident in the higher waist/hip ratios, particularly in men (p < 0.05). The associations were particularly strong (p < 0.001) for tobacco cigarette smoking and marijuana smoking, with roughly a 1.5 times higher prevalence in the top hostility quartile compared with the bottom quartile after adjusting for age and education. Hostility levels were not related to the percentage of calories from fat or from sucrose intake, to plasma cholesterol levels, or to physical fitness (except for a weak association in the latter in white women). The results describe relations between hostility and health behaviors that may be detrimental to health. The findings provide a possible explanation for the association between hostility and coronary heart disease mortality. C1 W ALABAMA HLTH SERV INC,EUTAW,AL. KAISER PERMANENTE,OAKLAND,CA. NHLBI,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. UNIV ALABAMA,BIRMINGHAM,AL 35294. FU NHLBI NIH HHS [N01-HC-48048, N01-HC-48049, N01-HC-48047] NR 43 TC 140 Z9 140 U1 0 U2 4 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUL 15 PY 1992 VL 136 IS 2 BP 136 EP 145 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA JN541 UT WOS:A1992JN54100002 PM 1415137 ER PT J AU ZHENG, W BLOT, WJ SHU, XO GAO, YT JI, BT ZIEGLER, RG FRAUMENI, JF AF ZHENG, W BLOT, WJ SHU, XO GAO, YT JI, BT ZIEGLER, RG FRAUMENI, JF TI DIET AND OTHER RISK-FACTORS FOR LARYNGEAL-CANCER IN SHANGHAI, CHINA SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE ALCOHOL DRINKING; ASCORBIC ACID; CAROTENE; CASE-CONTROL STUDIES; DIET; LARYNGEAL NEOPLASMS; OCCUPATIONS; TOBACCO ID NASOPHARYNGEAL CARCINOMA; SALTED FISH; STOMACH-CANCER; COASTAL TEXAS; ALCOHOL; TOBACCO; EPIDEMIOLOGY; CONSUMPTION; EXPOSURE; SMOKING AB A population-based, case-control study of laryngeal cancer was conducted in Shanghai, China, during 1988-1990, in which 201 incident cases (177 males, 24 females) and 414 controls (269 males, 145 females) were interviewed. Cigarette smoking was the major risk factor, accounting for 86% of the male and 54% of the female cases. After adjusting for smoking, there was little increase in risk associated with drinking alcoholic beverages. Among men, cases more often reported occupational exposures to asbestos and coal dust. A protective effect was associated with the intake of fruits (particularly oranges and tangerines), certain dark green/yellow vegetables, and garlic, but there was an increased risk with the intake of salt-preserved meat and fish. The findings suggest that risk factors for laryngeal cancer in Shanghai resemble those in Western countries, and they provide further evidence that dietary factors play an important etiologic role. C1 SHANGHAI CANC INST,DEPT EPIDEMIOL,SHANGHAI,PEOPLES R CHINA. RP ZHENG, W (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,ROOM 431,BETHESDA,MD 20892, USA. NR 45 TC 102 Z9 107 U1 1 U2 6 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUL 15 PY 1992 VL 136 IS 2 BP 178 EP 191 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA JN541 UT WOS:A1992JN54100006 PM 1415140 ER PT J AU BACH, LA THOTAKURA, NR RECHLER, MM AF BACH, LA THOTAKURA, NR RECHLER, MM TI HUMAN INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-6 IS O-GLYCOSYLATED SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID SERUM C1 NIDDKD,MOLEC & CELLULAR ENDOCRINOL BRANCH,MOLEC REGULAT & NEUROENDOCRINOL SECT,BETHESDA,MD 20892. RP BACH, LA (reprint author), NIDDKD,GROWTH & DEV SECT,BETHESDA,MD 20892, USA. OI Bach, Leon/0000-0002-9062-1518 NR 16 TC 60 Z9 61 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 15 PY 1992 VL 186 IS 1 BP 301 EP 307 DI 10.1016/S0006-291X(05)80807-1 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JE599 UT WOS:A1992JE59900041 PM 1378724 ER PT J AU SCANLON, MN LAZARWESLEY, E CSIKOS, T KUNOS, G AF SCANLON, MN LAZARWESLEY, E CSIKOS, T KUNOS, G TI RAT HYPOTHALAMIC PROOPIOMELANOCORTIN MESSENGER-RNA IS UNAFFECTED BY ADRENALECTOMY SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID OPIOMELANOCORTIN POMC GENE; RIBONUCLEIC-ACID; GLUCOCORTICOIDS; DEXAMETHASONE; EXPRESSION; SECRETION; PITUITARY; HORMONE; SYSTEM RP SCANLON, MN (reprint author), NIAAA,MOLEC & CELLULAR NEUROBIOL LAB,BETHESDA,MD 20892, USA. NR 17 TC 19 Z9 19 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 JUL 15 PY 1992 VL 186 IS 1 BP 418 EP 425 DI 10.1016/S0006-291X(05)80824-1 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JE599 UT WOS:A1992JE59900058 PM 1632781 ER PT J AU LOPEZAPARICIO, P RASCON, A MANGANIELLO, VC ANDERSSON, KE BELFRAGE, P DEGERMAN, E AF LOPEZAPARICIO, P RASCON, A MANGANIELLO, VC ANDERSSON, KE BELFRAGE, P DEGERMAN, E TI INSULIN INDUCED PHOSPHORYLATION AND ACTIVATION OF THE CGMP-INHIBITED CAMP PHOSPHODIESTERASE IN HUMAN PLATELETS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID DEPENDENT PROTEIN-KINASE; RAT ADIPOCYTES; FAT-CELLS; ADENYLATE-CYCLASE; RECEPTOR; STIMULATION; SUBSTRATE; MEMBRANE C1 UNIV LUND,DEPT CLIN PHARMACOL,S-22100 LUND,SWEDEN. NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892. RP LOPEZAPARICIO, P (reprint author), UNIV LUND,DEPT MED & PHYSIOL CHEM,POB 94,S-22100 LUND,SWEDEN. NR 26 TC 40 Z9 41 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 JUL 15 PY 1992 VL 186 IS 1 BP 517 EP 523 DI 10.1016/S0006-291X(05)80838-1 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JE599 UT WOS:A1992JE59900072 PM 1321613 ER PT J AU HIGLEY, JD SUOMI, SJ LINNOILA, M AF HIGLEY, JD SUOMI, SJ LINNOILA, M TI A LONGITUDINAL ASSESSMENT OF CSF MONOAMINE METABOLITE AND PLASMA-CORTISOL CONCENTRATIONS IN YOUNG RHESUS-MONKEYS SO BIOLOGICAL PSYCHIATRY LA English DT Article ID CEREBROSPINAL-FLUID MEASURES; BIOGENIC-AMINE METABOLISM; 5-HYDROXYINDOLEACETIC ACID; HOMOVANILLIC-ACID; MACACA-MULATTA; REARING CONDITIONS; SOCIAL SEPARATION; INFANTS; RESPONSES; CHILDREN AB Twenty-two rhesus macaques were studied longitudinally from infancy to early adolescence in order to assess the effects of developmental change, experimental history, gender, and individual variation on the response of the catecholaminergic, serotonergic, and adrenocortical systems to separation-induced stress. Experimental effects were assessed by comparing subjects reared for the first 6 months of life either with their mothers or in peer groups. Developmental changes in response to repeated separation stress were assessed by subjecting the monkeys to four sequential 4-day social separations when they were 6 and 18 months old. At both ages, prior to, and on the last day of the first and fourth separations, cerebrospinal fluid (CSF) was obtained from the cisterna magna to assess monoamine metabolite concentrations, and blood samples were collected to assess plasma cortisol concentrations. Blood samples were also obtained on the first day of each separation at each age. Age-related declines were found in both homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations for all subjects. Social separation consistently increased CSF 3-methoxy-4-hydroxyphenolglycol (MHPG) over baseline levels, but decreased HVA concentrations, whereas 5-HIAA levels increased following the first, but not the fourth separation. Plasma cortisol increased rapidly immediately after separation and remained higher than baseline on day 4 of both the first and fourth separation. Independent of age and experimental condition, peer-rearing increased CSF MHPG and plasma cortisol concentrations. During year 1, peer-rearing also produced diminished CSF 5-HIAA concentrations in female monkeys relative to female mother-reared monkeys, but increased male peer-reared monkeys' concentrations relative to mother-reared males. Interindividual differences were highly stable, with significant correlations both within and between years for each of the three metabolites and cortisol. C1 NIAAA,CLIN STUDIES LAB,ROCKVILLE,MD 20852. NICHHD,COMPARAT ETHOL LAB,BETHESDA,MD. NR 49 TC 173 Z9 173 U1 1 U2 5 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 JUL 15 PY 1992 VL 32 IS 2 BP 127 EP 145 DI 10.1016/0006-3223(92)90016-S PG 19 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA JU820 UT WOS:A1992JU82000002 PM 1384725 ER PT J AU LAL, RB RUDOLPH, DL COLIGAN, JE BRODINE, SK ROBERTS, CR AF LAL, RB RUDOLPH, DL COLIGAN, JE BRODINE, SK ROBERTS, CR TI FAILURE TO DETECT EVIDENCE OF HUMAN T-LYMPHOTROPIC VIRUS (HTLV) TYPE-I AND TYPE-II IN BLOOD-DONORS WITH ISOLATED GAG ANTIBODIES TO HTLV-I/II SO BLOOD LA English DT Article ID MONOCLONAL-ANTIBODY; INFECTION; SEQUENCE; ANTIGEN; PROTEINS; HOMOLOGY; DEFINES; REGION C1 NIAID,BIOL RESOURCE BRANCH,BETHESDA,MD 20892. USN HOSP,HLTH RES CTR,SAN DIEGO,CA 92134. WALTER REED ARMY MED CTR,DEPT DIAGNOST RETROVIROL,WASHINGTON,DC 20307. RP LAL, RB (reprint author), CTR DIS CONTROL,NATL CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,ATLANTA,GA 30333, USA. NR 35 TC 58 Z9 59 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 JUL 15 PY 1992 VL 80 IS 2 BP 544 EP 550 PG 7 WC Hematology SC Hematology GA JD588 UT WOS:A1992JD58800033 PM 1627806 ER PT J AU ALBORESSAAVEDRA, J HENSON, DE SOBIN, LH AF ALBORESSAAVEDRA, J HENSON, DE SOBIN, LH TI THE WHO HISTOLOGICAL CLASSIFICATION OF TUMORS OF THE GALLBLADDER AND EXTRAHEPATIC BILE-DUCTS - A COMMENTARY ON THE 2ND EDITION SO CANCER LA English DT Article ID BILIARY PAPILLOMATOSIS; CARCINOMA INSITU; ADENOCARCINOMA; CHOLECYSTITIS; HISTOGENESIS; HYPERPLASIA; PANCREAS; CELLS; TREE AB The second edition of the WHO Histological Classification of Tumors of the Gallbladder and Extrahepatic Bile Ducts is more comprehensive and detailed than the previous one. Advances in our understanding of dysplasia, carcinoma in situ, various lines of differentiation among the carcinomas, and the recognition of a variety of tumor-like lesions have resulted in more than three times as many entities in the current classification as in the previous one. The new edition should facilitate pathologic, epidemiologic, and therapeutic comparisons. C1 ARMED FORCES INST PATHOL,WHO,COLLABORATING CTR INT HISTOL CLASSIFICAT TUMORS,WASHINGTON,DC 20306. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. ARMED FORCES INST PATHOL,DIV GASTROINTESTINAL PATHOL,WASHINGTON,DC 20306. RP ALBORESSAAVEDRA, J (reprint author), UNIV TEXAS,SW MED CTR,DEPT PATHOL,5323 HARRY HINES BLVD,DALLAS,TX 75235, USA. NR 39 TC 65 Z9 72 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 0008-543X J9 CANCER JI Cancer PD JUL 15 PY 1992 VL 70 IS 2 BP 410 EP 414 DI 10.1002/1097-0142(19920715)70:2<410::AID-CNCR2820700207>3.0.CO;2-R PG 5 WC Oncology SC Oncology GA JC673 UT WOS:A1992JC67300006 PM 1617591 ER PT J AU SHU, XO BRINTON, LA ZHENG, W SWANSON, CA HATCH, MC GAO, YT FRAUMENI, JF AF SHU, XO BRINTON, LA ZHENG, W SWANSON, CA HATCH, MC GAO, YT FRAUMENI, JF TI RELATION OF OBESITY AND BODY-FAT DISTRIBUTION TO ENDOMETRIAL CANCER IN SHANGHAI, CHINA SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER; FOLLOW-UP; MEXICAN-AMERICANS; ADIPOSE-TISSUE; WOMEN; RISK; CARCINOMA; ESTROGENS; MASS AB In a case-control study involving 268 cases of endometrial cancer and an equal number of population controls, we assessed the relationship of risk to body weight and fat distribution, examining weight at various ages and current anthropometric measurements. Weight gain during later adulthood and resultant high body masses were important risk predictors, indicating that obesity is an important risk factor, even in an area where the prevalence of obesity and incidence of endometrial cancer are low. Certain fat distribution patterns were related to risk of endometrial cancer independent of general obesity. In particular, fat deposits on the trunk were associated with elevated risks, with the odds ratio for the highest versus lowest quartile of subscapular skinfolds remaining significant even after adjustment for body mass index (odds ratio = 2.9; 95% confidence interval, 1.1-7.3). Central versus peripheral obesity, as measured by the subscapular:triceps ratio, also was related to increased risk, although the association failed to remain significant after adjustment for body mass (highest to lowest quartile, odds ratio = 1.7). In contrast, upper body obesity, as assessed by the waist:thigh ratio, was unrelated to risk. These results support the need for future studies assessing the relationship of hormonal and other biological parameters of fat distribution to assist in identifying causal mechanisms for this tumor. C1 NCI,ENVIRONM EPIDEMIOL BRANCH,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,ROOM 443,BETHESDA,MD 20892. SHANGHAI CANC INST,DEPT EPIDEMIOL,SHANGHAI 20032,PEOPLES R CHINA. COLUMBIA UNIV,DIV EPIDEMIOL,NEW YORK,NY 10032. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 31 TC 49 Z9 53 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 JUL 15 PY 1992 VL 52 IS 14 BP 3865 EP 3870 PG 6 WC Oncology SC Oncology GA JC586 UT WOS:A1992JC58600006 PM 1617661 ER PT J AU PAULL, KD LIN, CM MALSPEIS, L HAMEL, E AF PAULL, KD LIN, CM MALSPEIS, L HAMEL, E TI IDENTIFICATION OF NOVEL ANTIMITOTIC AGENTS ACTING AT THE TUBULIN LEVEL BY COMPUTER-ASSISTED EVALUATION OF DIFFERENTIAL CYTOTOXICITY DATA SO CANCER RESEARCH LA English DT Article ID POLYMERIZATION; COLCHICINE; HYDROLYSIS; DERIVATIVES; INHIBITION; BINDING; DRUGS AB Data generated in the new National Cancer Institute drug evaluation program, which are based on inhibition of cell growth in 60 human tumor cell lines, were probed with nine known antimitotic agents using the COMPARE algorithm. Cytotoxicity data were available on approximately 7000 compounds at the time of the analysis, and, based on the criteria used, 82 compounds were selected as positive by the computer search. Nine were the probe compounds themselves, and 41 were analogues of known antimitotic agents. Among the remaining 32 compounds there were 19 distinct chemical species. Agents in ten of these groups (containing 20 compounds) were effective inhibitors of in vitro tubulin polymerization and caused the mitotic arrest of cells grown in culture. Two compounds were related natural products binding in the Vinca domain of tubulin, and the others were synthetic agents which interfered with colchicine binding. The remaining 12 agents (one natural product, the remainder synthetic) fell into several groups: two compounds were weak inhibitors of tubulin polymerization, inhibited colchicine binding, and caused mitotic arrest; one compound weakly inhibited tubulin polymerization but did not cause an increase in the number of cells arrested in mitosis; two compounds caused mitotic arrest at micromolar concentrations, but thus far no in vitro interaction with tubulin has been observed; the remainder neither inhibited tubulin polymerization nor caused a rise in the number of cultured cells arrested in mitosis. Tubulin-dependent GTP hydrolysis was stimulated or inhibited by all agents which inhibited tubulin polymerization with the exception of one compound. The analysis of differential cytotoxicity data thus appears to have great promise for the identification of new antimitotic agents with antineoplastic potential. C1 NCI,MOLEC PHARMACOL LAB,BLDG 37,ROOM 5C25,BETHESDA,MD 20892. NCI,INFORMAT TECHNOL BRANCH,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,FREDERICK,MD 21701. NR 26 TC 173 Z9 176 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 JUL 15 PY 1992 VL 52 IS 14 BP 3892 EP 3900 PG 9 WC Oncology SC Oncology GA JC586 UT WOS:A1992JC58600011 PM 1617665 ER PT J AU FONTANA, JA NERVI, C SHAO, ZM JETTEN, AM AF FONTANA, JA NERVI, C SHAO, ZM JETTEN, AM TI RETINOID ANTAGONISM OF ESTROGEN-RESPONSIVE TRANSFORMING GROWTH FACTOR-ALPHA AND PS2 GENE-EXPRESSION IN BREAST-CARCINOMA CELLS SO CANCER RESEARCH LA English DT Article ID MAMMARY EPITHELIAL-CELLS; BENZOIC-ACID DERIVATIVES; CANCER-CELLS; FACTOR RECEPTOR; PLASMINOGEN ACTIVATOR; BIOLOGICAL-ACTIVITIES; BINDING-PROTEIN; TGF-ALPHA; WILD-TYPE; MCF-7 AB Exposure of MCF-7 breast carcinoma cells to estradiol results in an increase in transforming growth factor-alpha (TGF-alpha) synthesis and secretion. Since TGF-alpha is a potent inducer of proliferation in MCF-7 cells, the increase in TGF-alpha production by estradiol is thought to play an important role in the estrogen stimulation of growth of these cells. Retinoic acid inhibits the proliferation of MCF-7 cells and antagonizes the estrogen stimulation of growth. Addition of retinoic acid resulted in a greater than 70% inhibition of estradiol-induced TGF-alpha synthesis and secretion in MCF-7 cells. The increase in TGF-alpha mRNA expression by estradiol was also inhibited by exposure of the cells to retinoic acid. Pretreatment of the cells with retinoic acid for 24 or 72 h caused more than 50 and 90% inhibition, respectively, of the estradiol-enhanced expression of TGF-alpha mRNA. Expression of pS2 mRNA in MCF-7 cells was stimulated approximately 8-fold by estradiol. Retinoic acid treatment suppressed by greater than 80% both the basal and estradiol-induced pS2 mRNA expression. Retinoic acid modulation of the estrogen receptor gene mRNA was not responsible for the retinoic acid inhibition of the stimulation of pS2 and TGF-alpha gene expression by estradiol, since estrogen receptor gene expression was increased rather than decreased in the presence of retinoic acid. The nuclear retinoic acid receptors-alpha and gamma mRNA were expressed in MCF-7 cells and its retinoic acid-resistant derivative RROI. Addition of estradiol to NICF-7 cells resulted in a decreased expression of retinoic acid receptor-gamma mRNA; this reduction is prevented by the presence of retinoic acid. These results indicate that retinoic acid can inhibit estradiol-induced TGF-alpha and pS2 mRNA expression in NICF-7 cells. The suppression of TGF-alpha expression may represent one possible mechanism by which retinoic acid antagonizes the stimulation of NICF-7 proliferation by estradiol. C1 VET ADM MED CTR,BALTIMORE,MD 21218. NIEHS,PULM PATHOBIOL LAB,CELL BIOL SECT,RES TRIANGLE PK,NC 27709. RP FONTANA, JA (reprint author), UNIV MARYLAND,CTR CANC,DEPT MED,ROOM 59D05,22 S GREENE ST,BALTIMORE,MD 21201, USA. OI Jetten, Anton/0000-0003-0954-4445; Fontana, Joseph/0000-0003-3829-3358 NR 68 TC 63 Z9 63 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 JUL 15 PY 1992 VL 52 IS 14 BP 3938 EP 3945 PG 8 WC Oncology SC Oncology GA JC586 UT WOS:A1992JC58600018 PM 1319834 ER PT J AU WETTERHAHN, KE DEMPLE, B KULESZMARTIN, M COPELAND, ES AF WETTERHAHN, KE DEMPLE, B KULESZMARTIN, M COPELAND, ES TI WORKSHOP REPORT FROM THE DIVISION OF RESEARCH GRANTS, NATIONAL-INSTITUTES-OF-HEALTH - METAL CARCINOGENESIS - A CHEMICAL PATHOLOGY STUDY SECTION WORKSHOP SO CANCER RESEARCH LA English DT Editorial Material ID DNA DAMAGE C1 HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. ROSWELL PK CANC INST,BUFFALO,NY 14263. NIH,DIV RES GRANTS,BETHESDA,MD 20892. RP WETTERHAHN, KE (reprint author), DARTMOUTH COLL,HANOVER,NH 03755, USA. NR 10 TC 14 Z9 14 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 JUL 15 PY 1992 VL 52 IS 14 BP 4058 EP 4063 PG 6 WC Oncology SC Oncology GA JC586 UT WOS:A1992JC58600038 PM 1617683 ER PT J AU PARK, JS LUETHY, JD WANG, MG FARGNOLI, J FORNACE, AJ MCBRIDE, OW HOLBROOK, NJ AF PARK, JS LUETHY, JD WANG, MG FARGNOLI, J FORNACE, AJ MCBRIDE, OW HOLBROOK, NJ TI ISOLATION, CHARACTERIZATION AND CHROMOSOMAL LOCALIZATION OF THE HUMAN GADD153 GENE SO GENE LA English DT Article DE DNA DAMAGE; METHYL METHANESULFONATE; 12-O-TETRADECANOYLPHORBOL-13-ACETATE; GENE REGULATION; TRANSCRIPTIONAL REGULATION ID INSITU HYBRIDIZATION; NUCLEOTIDE-SEQUENCE; ACTIVATION; DNA; VIRUS; IDENTIFICATION; PROMOTER; BINDING; COMPLEX; REGION AB We report the isolation and characterization of the growth arrest and DNA-damage-inducible gene, GADD153, from human cells and show that it is localized in the region 12q13.1-q13.2 on chromosome 12. Comparison of the human gene with the previously described hamster gene revealed a high level of conservation in both the structural and regulatory regions of the genes. Each is composed of four exons with intron/exon junctions maintained at the identical positions. The human Gadd153 protein shares 91% identity with the hamster protein in amino acid sequence, and 78% identity in nucleotide sequence. A 900-bp fragment of 5' flanking sequence from the human gene, when linked to the bacterial cat reporter gene, was found to exhibit promoter activity in HeLa cells which could be further activated by treatment with the DNA alkylating agent, methyl methanesulfonate. Sequence analysis indicated that the human promoter region is relatively G+C-rich and contains putative binding sites for multiple transcription factors, including recognition sites for TATA- and CAAT-binding proteins, six Sp1-binding sites, an activator protein-1 binding site, an E-26-specific sequence-binding protein-1 DNA-binding site, and four interleukin-6 response elements. Many of these sites are also present in an identical position in the hamster gene suggesting they may play an important role in regulating GADD153 expression. C1 NIA,GERONTOL RES CTR,MOLEC GENET LAB,4940 EASTERN AVE,BALTIMORE,MD 21224. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 26 TC 116 Z9 117 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUL 15 PY 1992 VL 116 IS 2 BP 259 EP 267 DI 10.1016/0378-1119(92)90523-R PG 9 WC Genetics & Heredity SC Genetics & Heredity GA JF008 UT WOS:A1992JF00800017 PM 1339368 ER PT J AU TRACER, HL LOH, YP BIRCH, NP AF TRACER, HL LOH, YP BIRCH, NP TI RAT MITOCHONDRIAL COUPLING FACTOR-6 - MOLECULAR-CLONING OF A CDNA-ENCODING THE IMPORTED PRECURSOR SO GENE LA English DT Note DE H+-TRANSPORTING ATPASE; RECOMBINANT DNA; NUCLEOTIDE AND AMINO ACID SEQUENCE ID OXIDATIVE-PHOSPHORYLATION; ATP SYNTHASE; SEQUENCE; PROTEIN AB A cDNA clone encoding the precursor to the rat mitochondrial protein coupling factor 6 (F6) has been isolated and sequenced. The deduced amino acid sequence of the rat precursor protein shows 78% and 74% identity with the human and bovine F6 pre-proteins, respectively. C1 NICHHD,DEV NEUROBIOL LAB,CELLULAR NEUROBIOL SECT,BLDG 36,RM 2A21,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. RI Birch, Nigel/H-2498-2011 OI Birch, Nigel/0000-0002-8417-3587 NR 10 TC 0 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUL 15 PY 1992 VL 116 IS 2 BP 291 EP 292 DI 10.1016/0378-1119(92)90528-W PG 2 WC Genetics & Heredity SC Genetics & Heredity GA JF008 UT WOS:A1992JF00800022 PM 1386054 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 BREAST-CANCER RP KARP, JE (reprint author), NCI,BETHESDA,MD 20892, USA. NR 17 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 JUL 15 PY 1992 VL 268 IS 3 BP 391 EP 393 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA JC352 UT WOS:A1992JC35200043 PM 1613930 ER PT J AU LOYA, S TAL, R HUGHES, SH HIZI, A AF LOYA, S TAL, R HUGHES, SH HIZI, A TI THE EFFECTS OF CYSTEINE MUTATIONS ON THE CATALYTIC ACTIVITIES OF THE REVERSE-TRANSCRIPTASE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT DNA-POLYMERASE; ESCHERICHIA-COLI; RETROVIRUS; AIDS AB The reverse transcriptase (RT) of the human immunodeficiency virus type 1 (HIV-1) has only 2 cysteine residues at positions 38 and 280. In order to investigate the role of these cysteines in the structure and function of the enzyme, we have previously modified each of the cysteines to serines employing site-directed mutagenesis. Two of the mutant forms of HIV-1 RT, the single mutant of cysteine 280 and a double mutant with both cysteines modified, were purified. In the present study we have compared the catalytic properties of the DNA-polymerizing and the ribonuclease H (RNase H) functions of the two mutant RTs to those of the native enzyme. The results indicate that the single mutant RT closely resembles the wild type enzyme in almost all the catalytic functions tested. The double cysteine mutant RT, on the other hand, exhibits several unique features. First, the specific activities of the RNA- and DNA-directed DNA synthesis are significantly lower than the corresponding activities of the other two enzymes. This probably results from the lower V(max) values exhibited by the double mutant RT, since the K(m) values calculated for all enzymes were similar. Second, the most outstanding differences are associated with the RNase H activity of the double mutant RT. The specific activity of RNase H is about 4-fold higher than the wild type and the single mutant RTs. Furthermore, the heat stability of the RNase H function of the double mutated RT is at least 15-fold higher than that of the other two RTs. The substantial resistance to heat denaturation is apparent only for the RNase H activity, since the DNA polymerizing function of the double mutant RT is as sensitive to heat denaturation as the other two proteins. C1 TEL AVIV UNIV,SACKLER SCH MED,DEPT CELL BIOL & HISTOL,IL-69978 TEL AVIV,ISRAEL. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21701. FU NCI NIH HHS [N01-CO-74101]; NIAID NIH HHS [R0I-AI 27035] NR 29 TC 15 Z9 15 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 JUL 15 PY 1992 VL 267 IS 20 BP 13879 EP 13883 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JD325 UT WOS:A1992JD32500017 PM 1378433 ER PT J AU TEAGUE, WE DOBSON, GP AF TEAGUE, WE DOBSON, GP TI EFFECT OF TEMPERATURE ON THE CREATINE-KINASE EQUILIBRIUM SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SATURATION-TRANSFER; SKELETAL-MUSCLE; ATP SYNTHESIS; RAT-HEART AB The effect of temperature on the apparent equilibrium constant of creatine kinase (ATP:creatine N-phosphotransferase (EC 2.7.3.2)) was determined. At equilibrium the apparent K' for the biochemical reaction was defined as K' = [SIGMA-ATP][Cr]/[SIGMA-ADP][SIGMA-PCr] The symbol SIGMA-denotes the sum of all the ionic and metal complex species of the reactant components in m. The K' at pH 7.0, 1.0 mM free Mg2+, and ionic strength of 0.25 M at experimental conditions was 177 +/- 7.0, 217 +/- 11, 255 +/- 10, and 307 +/- 13 (n = 8) at 38, 25, 15, and 5-degrees-C, respectively. The standard apparent enthalpy or heat of the reaction at the specified conditions (DELTA-H'degrees) was calculated from a van't Hoff plot of log10.K' versus 1/T, and found to be -11.93 kJ mol-1 (-2852 cal mol-1) in the direction of ATP formation. The corresponding standard apparent entropy of the reaction (DELTA-S'degrees) was +4.70 J K-1 mol-1. The linear function (r2 = 0.99) between log10 K' and 1/K demonstrates that both DELTA-H'degrees and DELTA-S'degrees are independent of temperature for the creatine kinase reaction, and that DELTA-C(p)'degrees, the standard apparent heat capacity of products minus reactants in their standard states, is negligible between 5 and 38-degrees-C. We further show from our data that the sign and magnitude of the standard apparent Gibbs energy (DELTA-G'degrees) of the creatine kinase reaction was comprised mostly of the enthalpy of the reaction, with 11% coming from the entropy T-DELTA-S'degrees term. The thermodynamic quantities for the following two reference reactions of creatine kinase were also determined. PCr2- + ADP3- + H+ = ATP4- + Cr (2) MgPCr + MgADP1- + H+ = MgATP2- + Cr + Mg2+ (3) The DELTA-H-degrees for Reaction 2 was -16.73 kJ mol-1 (-3998 cal mol-1) and for Reaction 3 was -23.23 kJ mol-1 (-5552 cal mol-1) over the temperature range 5-38-degrees-C. The corresponding DELTA-S-degrees values for the reactions were +110.43 and +83.49 J K-1 mol-1, respectively. Using the DELTA-H'degrees of -11.93 kJ mol-1, and one K' value at one temperature, a second K' at a second temperature can be calculated, thus permitting bioenergetic investigations of organs and tissues using the creatine kinase equilibria over the entire physiological temperature range. C1 NIAAA,12501 WASHINGTON AVE,ROCKVILLE,MD 20852. NR 30 TC 53 Z9 53 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 JUL 15 PY 1992 VL 267 IS 20 BP 14084 EP 14093 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JD325 UT WOS:A1992JD32500049 PM 1629208 ER PT J AU NOMIZU, M UTANI, A SHIRAISHI, N KIBBEY, MC YAMADA, Y ROLLER, PP AF NOMIZU, M UTANI, A SHIRAISHI, N KIBBEY, MC YAMADA, Y ROLLER, PP TI THE ALL-D-CONFIGURATION SEGMENT CONTAINING THE IKVAV SEQUENCE OF LAMININ A-CHAIN HAS SIMILAR ACTIVITIES TO THE ALL-L-PEPTIDE INVITRO AND INVIVO SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMINO-ACID-SEQUENCE; SYNTHETIC PEPTIDE; CELL-ADHESION; NEURITE OUTGROWTH; IDENTIFICATION; GLYCOPROTEIN; ATTACHMENT; RESISTANCE; SECONDARY; PROTEINS AB Laminin is a basement membrane glycoprotein that has diverse biological activities. A sequence on the A chain containing IKVAV (Ile-Lys-Val-Ala-Val) has been shown to promote neurite outgrowth, cell adhesion, and tumor growth and metastasis. Here we have determined the structural requirements of this synthetic peptide for biological activity. Twelve-amino acid-long all-L- (LAM-L) and all-D-peptide (LAM-D) segments as well as an alternating D- and L-amino acid-containing peptide (LAM-DL), which included the IKVAV sequence (residues 2097-2108), were synthesized. Circular dichroism spectral analysis revealed a mirror image conformation of LAM-D and LAM-L with mainly beta-sheet and to a minor extent alpha-helical structure. LAM-DL did not exhibit any significant ordered conformational features. LAM-D and LAM-L showed similar cell attachment activities for rat pheochromocytoma cells (PC12), whereas LAM-DL was inactive. A peptide analog with randomized IKVAV sequence (LAM-RM) was also inactive. A similar trend was observed in competition experiments of the four peptides with laminin in analogous cell attachment assays. In in vivo experiments, both LAM-D and LAM-L were capable of increasing tumor growth when subcutaneously injected into mice with murine melanoma cells B16F10. Results indicate that the conformational status of the IKVAV domain is a contributing factor in determining the biological activity but that there is no strict requirement for a specific chirality. There is a likely sequence specificity to the IKVAV region. C1 NCI,DIV CANC TREATMENT,MEDICINAL CHEM LAB,DEV THERAPEUT PROGRAM,BLDG 37,RM 5C02,BETHESDA,MD 20892. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NR 32 TC 40 Z9 40 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 15 PY 1992 VL 267 IS 20 BP 14118 EP 14121 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JD325 UT WOS:A1992JD32500053 PM 1629212 ER PT J AU KONG, SK CHOCK, PB AF KONG, SK CHOCK, PB TI PROTEIN UBIQUITINATION IS REGULATED BY PHOSPHORYLATION - AN INVITRO STUDY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE KINASE; HISTONES; IDENTIFICATION; DISAPPEARANCE; PURIFICATION; MECHANISM; ISOZYMES; SPLEEN; ENZYME; CELLS AB Protein ubiquitination has been implicated in ATP-dependent protein turnover and in a number of biological processes in eukaryotic cells. The ubiquitination activating enzyme, E1, and ubiquitin carrier protein, E2, are two essential enzymes in the protein ubiquitination machinery. Using purified E1 and E2 from rabbit reticulocytes and various protein kinases, which include cAMP-dependent protein kinase, protein kinase C, and protein tyrosine kinase, we demonstrated that E1 is phosphorylated by protein kinase C, with a stoichiometry of 0.65 mol of phosphate/mol of E1, and one of the E2 isoforms, E2(32kDa), is phosphorylated by protein tyrosine kinase to 2 eq of phosphate/mol of protein. Phosphorylation of E1 causes a 2- fold enhancement of its activity as monitored by ubiquitin-dependent ATP half arrow left over half arrow right PP(i) exchange. When 1 eq of phosphate was incorporated into E2(32kDa), a 2.4-fold activation was also observed for its activity to catalyze the ubiquitination of histone H2A. The regulatory significance of this finding is discussed. RP KONG, SK (reprint author), NHLBI,BIOCHEM LAB,BETHESDA,MD 20892, USA. NR 31 TC 41 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 JUL 15 PY 1992 VL 267 IS 20 BP 14189 EP 14192 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JD325 UT WOS:A1992JD32500063 PM 1321138 ER PT J AU IWATA, K KENSHALO, DR DUBNER, R NAHIN, RL AF IWATA, K KENSHALO, DR DUBNER, R NAHIN, RL TI DIENCEPHALIC PROJECTIONS FROM THE SUPERFICIAL AND DEEP LAMINAE OF THE MEDULLARY DORSAL HORN IN THE RAT SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE TRIGEMINAL; HYPOTHALAMUS; THALAMUS; PHA-L; PAIN ID LATERAL HYPOTHALAMIC NEURONS; THERMAL DISCRIMINATION TASK; SPINOTHALAMIC TRACT NEURONS; CAUDAL TRIGEMINAL NUCLEUS; LEUKOAGGLUTININ PHA-L; BRAIN-STEM NEURONS; SPINAL-CORD; HORSERADISH-PEROXIDASE; TOOTH-PULP; NOXIOUS STIMULI AB An important function of the medullary dorsal horn (MDH) is the relay of nociceptive information from the face and mouth to higher centers of the central nervous system. We studied the central projection pattern of axons arising from the MDH by examining the axonal transport of Phaseolus vulgaris-leucoagglutinin (PHA-L). Labeled axon and axon terminal distributions arising from the MDH were analyzed at the light microscopic level. After large injections of PHA-L into both superficial and deep laminae of the MDH in the rat, labeled axons were observed in the nucleus submedius of the thalamus (SUB), ventroposterior thalamic nucleus medialis (VPM), ventroposterior thalamic nucleus parvicellularis (VPPC), posterior thalamic nuclei (PO), zona incerta (ZI), lateral hypothalamic nucleus (LH), and posterior hypothalamic nucleus (PH). Restriction of PHA-L into only the superficial laminae resulted in heavy axon and varicosity labeling in the SUB, VPM, PO, and VPPC and light labeling in LH. In contrast, after injections into deep laminae, labeled axons were mainly distributed in ZI and PH; some were also in VPM and LH, and fewer still in PO and SUB. Varicosities in VPM, SUB, and PO were significantly larger than those in VPPC, ZI, LH, and PH. Varicosity density was highest in SUB and lowest in the VPPC. We concluded that there are two distinct nociceptive pathways, one originating from the superficial MDH and terminating primarily in the dorsal diencephalon and the second originating from deep laminae of the MDH and terminating primarily in the ventral diencephalon. We propose that in the rat, input from the deeper laminae is primarily involved in the motivational-affective component of pain, whereas input from the superficial MDH is related to both the sensory-discriminative and motivational-affective component of pain. RP IWATA, K (reprint author), NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892, USA. NR 96 TC 62 Z9 62 U1 0 U2 4 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 JUL 15 PY 1992 VL 321 IS 3 BP 404 EP 420 DI 10.1002/cne.903210308 PG 17 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA JC620 UT WOS:A1992JC62000007 PM 1506477 ER PT J AU BRISTOL, LA SAKAGUCHI, K APPELLA, E DOYLE, D TAKACS, L AF BRISTOL, LA SAKAGUCHI, K APPELLA, E DOYLE, D TAKACS, L TI THYMOCYTE COSTIMULATING ANTIGEN IS CD26 (DIPEPTIDYLPEPTIDASE-IV) - COSTIMULATION OF GRANULOCYTE, MACROPHAGE, AND T-LINEAGE CELL-PROLIFERATION VIA CD26 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOCYTES-T; ACTIVATION; EXPRESSION; RECEPTOR; CD3; IMMATURE; LEUKEMIA; SEQUENCE; MOLECULE; PROTEIN AB The rat thymocyte costimulating protein appears to be involved in the regulation of CD4-/CD8- thymocyte proliferation in vitro. We show that thymocyte costimulating protein is dipeptidyl peptidase IV (E.C.N.3.4.14.5) also known as CD26. Some bone marrow cells as well as CD4-/CD8- and, and to a lesser extent, more differentiated T cells respond by proliferating to a CD26 specific mAb-mediated costimulus that does not influence dipeptidyl dipeptidase IV enzyme activity. This suggests the existence of a CD26-linked regulatory mechanism of proliferation that is operational on granulocyte- and macrophage-lineage cells and throughout T cell development. C1 NIAAA,ALCOHOL DRUG ABUSE & MENTAL HLTH ADM,ROCKVILLE,MD 20852. SUNY BUFFALO,DEPT BIOL SCI,BUFFALO,NY 14260. NCI,CELL BIOL LAB,CHEM SECT,BETHESDA,MD 20892. NR 26 TC 31 Z9 31 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 1992 VL 149 IS 2 BP 367 EP 372 PG 6 WC Immunology SC Immunology GA JD122 UT WOS:A1992JD12200001 PM 1352525 ER PT J AU WADSWORTH, S HALVORSON, MJ COLIGAN, JE AF WADSWORTH, S HALVORSON, MJ COLIGAN, JE TI DEVELOPMENTALLY REGULATED EXPRESSION OF THE BETA-4 INTEGRIN ON IMMATURE MOUSE THYMOCYTES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID AMINO-ACID-SEQUENCE; EPITHELIAL-CELLS; MURINE THYMOCYTES; T-CELLS; RECEPTOR; SUBUNIT; ANTIGEN; THYMUS; BINDING; PROTEIN AB Integrins are a superfamily of alpha-beta heterodimers, most of which serve as cell surface receptors for extracellular matrix proteins. In this report, we demonstrate that the recently described alpha-6-beta-4 integrin, previously thought to be limited to epithelial cells and Schwann cells, is expressed on immature mouse thymocytes. The presence of alpha-6-beta-4 is controlled by regulation of beta-4 expression, because alpha-6 was expressed by virtually all cells examined, paired with the beta-1 integrin chain to form VLA-6. During fetal ontogeny, beta-4 was highly expressed by 35% of day-13 thymocytes, 75% of day-14 to -15 thymocytes, then rapidly declined to low levels by birth. In neonates and adults, beta-4 expression was highest on CD4- CD8- CD3- and TCR+-gamma-delta subsets. Correlation of IL-2R, CD44 and beta-4 on CD4- CD8- thymocytes revealed maximal levels on the intermediate CD44- IL-2R+ subset. Most CD4- CD8+ TCR- thymocytes and a significant fraction of CD4+ CD8+ thymocytes were beta-4lo, whereas the most mature J11d- single positive thymocytes were beta-4-. Overall, down-regulation Of beta-4 was associated with up-regulation of CD4, CD8, and CD3 in the thymus. alpha-6-beta-4 was undetectable on fetal liver or bone marrow cells, lymphocytes from lymph node, spleen, or blood, and mitogen-activated splenic T cells cultured up to 10 wk with IL-2. The data suggest that alpha-6-beta-4 is up-regulated after pro-T cells enter the thymus and may have a thymus-specific function for T cells. The developmentally regulated pattern of expression and the prominence Of alpha-6-beta-4 on day-13 to -16 fetal and adult CD4- CD8- CD3- thymocytes further suggest this unusual integrin may play a role in early T cell development, including stages before acquisition of the TCR. C1 NIAID,BIOL RESOURCES BRANCH,BLDG 4,ROOM 413,BETHESDA,MD 20892. NR 41 TC 61 Z9 61 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 JUL 15 PY 1992 VL 149 IS 2 BP 421 EP 428 PG 8 WC Immunology SC Immunology GA JD122 UT WOS:A1992JD12200008 PM 1385605 ER PT J AU HAMAWY, MM OLIVER, C MERGENHAGEN, SE SIRAGANIAN, RP AF HAMAWY, MM OLIVER, C MERGENHAGEN, SE SIRAGANIAN, RP TI ADHERENCE OF RAT BASOPHILIC LEUKEMIA (RBL-2H3) CELLS TO FIBRONECTIN-COATED SURFACES ENHANCES SECRETION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PERIPHERAL-BLOOD MONOCYTES; PROTEIN-KINASE-C; MAST-CELLS; 2H3 CELLS; HISTAMINE-RELEASE; SIGNAL TRANSDUCTION; ENDOTHELIAL-CELLS; MEDIATOR RELEASE; CALCIUM SIGNAL; IGE RECEPTORS AB Rat basophilic leukemia (RBL-2H3) cells are a useful in vitro model for studies of mast cells and basophils. We examined the adherence of RBL-2H3 cells to different extracellular matrix proteins and the effect of such attachment on secretion. The cells bound to fibronectin-coated surfaces with maximum binding by 1 h at 37-degrees-C. There was less attachment to laminin, collagen type I, and collagen type IV. There was no adherence to uncoated surfaces or in the absence of Ca2+. Binding to fibronectin was blocked by a synthetic peptide containing the sequence Arg-Gly-Asp. Therefore, the binding of RBL-2H3 cells to fibronectin may be mediated by surface molecules that belong to the integrin family. Adherence to fibronectin-coated surfaces resulted in cell spreading, a reorganization of the cytoskeletal elements, and a redistribution of the secretory granules. Attachment to fibronectin also dramatically enhanced high affinity IgE receptor-mediated histamine release. This enhancement was maximum by 1 h of adherence and lasted for at least 6 h. There was also enhanced secretion by the Ca2+ ionophore A23187. Thus, adherence to fibronectin can enhance both receptor and non-receptor-mediated release. Addition of soluble fibronectin to RBL-2H3 cells in suspension had no effect on secretion. Therefore, enhanced histamine release required cell attachment to immobilized fibronectin. These results suggest that secretion from mast cells/basophils may be modulated by their interaction with the extracellular matrix. C1 NIDR,IMMUNOL LAB,BLDG 10,ROOM 1N106,BETHESDA,MD 20892. RI Wan, Daniel/F-4689-2010 NR 50 TC 97 Z9 97 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 1992 VL 149 IS 2 BP 615 EP 621 PG 7 WC Immunology SC Immunology GA JD122 UT WOS:A1992JD12200035 PM 1378072 ER PT J AU CHAMAT, S NARA, P BERQUIST, L WHALLEY, A MORROW, WJW KOHLER, H KANG, CY AF CHAMAT, S NARA, P BERQUIST, L WHALLEY, A MORROW, WJW KOHLER, H KANG, CY TI 2 MAJOR GROUPS OF NEUTRALIZING ANTI-GP120 ANTIBODIES EXIST IN HIV-INFECTED INDIVIDUALS - EVIDENCE FOR EPITOPE DIVERSITY AROUND THE CD4 ATTACHMENT SITE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; MONOCLONAL-ANTIBODIES; GP120 BINDING; ENVELOPE GLYCOPROTEIN; RECEPTOR-BINDING; PROTEIN; ASSAY; ASSOCIATION; FRAGMENT; SERA AB The aim of this study was to dissect neutralizing anti-gp120 antibody populations in seropositive asymptomatic individuals. Murine anti-Id mAb were raised against polyclonal affinity-purified human anti-gp120 antibodies. These anti-Id mAb were used to fractionate anti-gp120 antibodies from a pool of HIV-positive sera into idiotypically distinct anti-gp120 antibody (Id+ Ab) preparations. Immunochemical and neutralization studies indicated that all Id+ Ab that neutralized HIV-I in vitro interacted with either the V3 loop or the CD4 attachment site of gp120. The V3-specific ld+ Ab neutralized HIV-1 in a strain-restricted manner. Id+ Ab specific for the CD4 attachment site exhibited different spectra of neutralizing activities against multiple strains of HIV-1. This finding indicates that multiple, antigenically diverse epitopes reside around the CD4 attachment site of gp120. Significantly, depletion of the Id+ Ab from affinity-purified total anti-gp120 antibodies abrogated most of the neutralizing activities of these antibodies, suggesting that neutralizing anti-gp120 antibodies consist of two major specificities, either to the V3 region or to the CD4 attachment site. The understanding of specificities and neutralizing activities of different anti-gp120 antibodies in seropositive healthy individuals will be helpful for designing effective vaccines and immunotherapeutic strategies for AIDS. C1 IDEC PHARMACEUT CORP,11099 N TORREY PINES RD,LA JOLLA,CA 92037. NCI,FREDERICK,MD 21701. FU NIAID NIH HHS [AI31310] NR 40 TC 48 Z9 48 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 JUL 15 PY 1992 VL 149 IS 2 BP 649 EP 654 PG 6 WC Immunology SC Immunology GA JD122 UT WOS:A1992JD12200040 PM 1378074 ER PT J AU STANLEY, SK KESSLER, SW JUSTEMENT, JS SCHNITTMAN, SM GREENHOUSE, JJ BROWN, CC MUSONGELA, L MUSEY, K KAPITA, B FAUCI, AS AF STANLEY, SK KESSLER, SW JUSTEMENT, JS SCHNITTMAN, SM GREENHOUSE, JJ BROWN, CC MUSONGELA, L MUSEY, K KAPITA, B FAUCI, AS TI CD34+ BONE-MARROW CELLS ARE INFECTED WITH HIV IN A SUBSET OF SEROPOSITIVE INDIVIDUALS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEMATOPOIETIC PROGENITOR CELLS; AIDS-RELATED COMPLEX; T-CELL; HOMOSEXUAL MEN; HEMATOLOGIC MANIFESTATIONS; HIV-1-INFECTED SUBJECTS; PERIPHERAL-BLOOD; INVITRO; ANTIGEN AB Individuals infected with HIV frequently develop cytopenias and suppressed hematopoiesis. The role of direct HIV infection of hematopoietic progenitor cells in this process has not been defined. In this study, purified CD34+ bone marrow progenitor cells from 74 Zairian and American patients were studied by both coculture viral isolation and polymerase chain reaction for evidence of HIV infection. A total of 36.5% of Zairian and 14% of American patients had HIV infection of the CD34+ cell subset, with as many as 1 in 500 CD34+ cells infected. Most of the Zairian patients in this study had advanced HIV infection and markedly decreased CD4/CD8 T lymphocyte ratios (mean 0.160 +/- 0.08), and no laboratory value predicted the presence of infection in the CD34+ subset of a given Zairian individual. In contrast, American patients with CD34+ cell infection had total CD4 cells <20/mm3 and a greater decrease of the CD4/CD8 T lymphocyte ratio compared to seropositive Americans without CD34+ cell infection (p = 0.003). Hematopoiesis, studied by methylcellulose colony assays, was depressed in all seropositive patients studied with no significant further suppression when CD34+ cells were infected. Thus, CD34+ bone marrow progenitor cells are infected in vivo in a subset of seropositive individuals and may serve as an additional reservoir of virus in HIV-infected individuals. C1 USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20889. MAMA YEMO HOSP,KINSHASA,ZAIRE. PROJECT SIDA,KINSHASA,ZAIRE. RP STANLEY, SK (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 31,ROOM 7A-03,BETHESDA,MD 20892, USA. NR 41 TC 141 Z9 142 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 JUL 15 PY 1992 VL 149 IS 2 BP 689 EP 697 PG 9 WC Immunology SC Immunology GA JD122 UT WOS:A1992JD12200046 PM 1378076 ER PT J AU KANTOR, J IRVINE, K ABRAMS, S KAUFMAN, H DIPIETRO, J SCHLOM, J AF KANTOR, J IRVINE, K ABRAMS, S KAUFMAN, H DIPIETRO, J SCHLOM, J TI ANTITUMOR-ACTIVITY AND IMMUNE-RESPONSES INDUCED BY A RECOMBINANT CARCINOEMBRYONIC ANTIGEN-VACCINIA VIRUS-VACCINE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID COLORECTAL-CANCER; IMMUNOTHERAPY; MELANOMA; ADJUVANT; TRIAL AB Background: Human carcinoembryonic antigen (CEA) is a 180-kd glycoprotein expressed in human colorectal, gastric, pancreatic, breast, and non-small-cell lung carcinomas. Previous studies have demonstrated enhanced immune responses to other antigens presented with vaccinia virus proteins via a recombinant vaccinia virus construct. In addition, we have developed a recombinant CEA-vaccinia virus construct, designated rV(WR)-CEA, and have demonstrated humoral anti-CEA responses in mice after immunization with that virus. Purpose: The goals of this study were (a) to construct a recombinant CEA-vaccinia vaccine in a less virulent vaccinia strain that is potentially safe and effective for treatment of patients whose tumors express CEA and (b) to evaluate the ability of the recombinant CEA-vaccinia vaccine to prevent and reverse tumor growth in mice and to elicit cell-mediated and humoral anti-CEA immune responses. Methods: Using. the New York City strain of vaccinia virus, which is.used in smallpox vaccination and is more attenuated for humans than rV(WR), we derived a recombinant CEA-vaccinia construct, designated rV(NYC)-CEA. The ability of this construct to induce antitumor immunity was evaluated in mice receiving subcutaneous injections of murine colon adenocarcinoma cells expressing the human CEA gene. Results: Administration of rV(NYC)-CEA in mice induced strong anti-CEA antibody responses, as well as CEA-specific cell-mediated responses, including delayed-type hypersensitivity, lympho-proliferative, and cytotoxic responses. Vaccination of mice with the rV(NYC)-CEA rendered them resistant to the growth of subsequently transplanted CEA-expressing tumors. Moreover, when mice were vaccinated 7 days after tumor cell injection, tumor growth was either greatly reduced or eliminated. No toxic effects were observed in any of the mice. Conclusion: These studies demonstrate that antitumor activity can be induced with the use of a recombinant CEA-vaccinia virus construct derived from an attenuated vaccinia strain, and they reveal the range of cell-mediated and humoral responses induced by this recombinant vaccine. C1 NCI,DIV CANC BIOL DIAG & CTR,BLDG 10,RM 8B07,BETHESDA,MD 20892. NR 25 TC 191 Z9 193 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 15 PY 1992 VL 84 IS 14 BP 1084 EP 1091 DI 10.1093/jnci/84.14.1084 PG 8 WC Oncology SC Oncology GA JC869 UT WOS:A1992JC86900013 PM 1619682 ER PT J AU HSING, AW MCLAUGHLIN, JK HOOVER, RN CHIEN, HTC BLOT, WJ FRAUMENI, JF AF HSING, AW MCLAUGHLIN, JK HOOVER, RN CHIEN, HTC BLOT, WJ FRAUMENI, JF TI PARITY AND PRIMARY LIVER-CANCER AMONG YOUNG-WOMEN SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Note ID ORAL-CONTRACEPTIVES; HEPATOCELLULAR-CARCINOMA RP HSING, AW (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,RM 415,BETHESDA,MD 20892, USA. NR 16 TC 11 Z9 11 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 JUL 15 PY 1992 VL 84 IS 14 BP 1118 EP 1119 DI 10.1093/jnci/84.14.1118 PG 2 WC Oncology SC Oncology GA JC869 UT WOS:A1992JC86900018 PM 1619686 ER PT J AU REVATHI, S VALSAKUMAR, MC BALAKRISHNAN, V WEISS, GH AF REVATHI, S VALSAKUMAR, MC BALAKRISHNAN, V WEISS, GH TI SIZE-DEPENDENT DIFFUSION-COEFFICIENT IN A MYOPIC RANDOM-WALK ON A STRIP SO PHYSICA A LA English DT Article ID PERCOLATION-THRESHOLD AB We consider a random walk in discrete time (n = 0, 1, 2, . . .) on a square lattice of finite width in the y-direction, i.e., {j, m\j is-an-element-of Z, m = 1, 2, 3,. . . ,N). A myopic walker at (j, 1) or (j, N) jumps with probability 1/3 to any of the available nearest-neighbor sites at the end of a time step. This couples the motions in the x- and y-directions, and leads to several interesting features, including a coefficient of diffusion in the x-direction that depends on the transverse size N of the strip. Explicit solutions for [x(n)2] (and the lateral variance [y(n)2]) are given for small values of N. A closed-form expression is obtained for the (discrete Laplace) transform of [x(n)2] for general N. The asymptotic behaviors of [x(n)2] and [y(n)2] are found, the corrections falling off exponentially with increasing n. The results obtained are generalized to a myopic random walk in d dimensions, and it is shown that the diffusion coefficient has an explicit geometry dependence involving the surface-to-volume ratio. This coefficient can therefore serve as a probe of the geometry of the structure on which diffusion takes place. C1 INDIRA GANDHI CTR ATOM RES,DIV MAT SCI,KALPAKKAM 603102,INDIA. NIH,PHYS SCI LAB,BETHESDA,MD 20892. RP REVATHI, S (reprint author), INDIAN INST TECHNOL,DEPT PHYS,MADRAS 600036,TAMIL NADU,INDIA. NR 11 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 J9 PHYSICA A JI Physica A PD JUL 15 PY 1992 VL 186 IS 1-2 BP 210 EP 219 DI 10.1016/0378-4371(92)90376-2 PG 10 WC Physics, Multidisciplinary SC Physics GA JH237 UT WOS:A1992JH23700016 ER PT J AU DAYAN, I GITTERMAN, M WEISS, GH AF DAYAN, I GITTERMAN, M WEISS, GH TI STOCHASTIC RESONANCE IN TRANSIENT DYNAMICS SO PHYSICAL REVIEW A LA English DT Article ID CLIMATIC TRANSITIONS; SYSTEM; NOISE AB Stochastic resonance has been examined in a number of systems that have steady states. We examine a dynamical system that allows for the escape of a particle from a potential well, and that is subjected to the combination of a periodic forcing term and noise. We show that in such a system the addition of a small amount of noise can actually increase the average time for the particle to escape from the well. This effect depends on the frequency of the external field and in this sense is a form of stochastic resonance. C1 NIH,BETHESDA,MD 20892. RP DAYAN, I (reprint author), BAR ILAN UNIV,DEPT PHYS,IL-52100 RAMAT GAN,ISRAEL. NR 17 TC 87 Z9 87 U1 2 U2 3 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 JUL 15 PY 1992 VL 46 IS 2 BP 757 EP 761 DI 10.1103/PhysRevA.46.757 PG 5 WC Optics; Physics, Atomic, Molecular & Chemical SC Optics; Physics GA JF183 UT WOS:A1992JF18300013 ER PT J AU LAKSO, M SAUER, B MOSINGER, B LEE, EJ MANNING, RW YU, SH MULDER, KL WESTPHAL, H AF LAKSO, M SAUER, B MOSINGER, B LEE, EJ MANNING, RW YU, SH MULDER, KL WESTPHAL, H TI TARGETED ONCOGENE ACTIVATION BY SITE-SPECIFIC RECOMBINATION IN TRANSGENIC MICE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CRE/LOX; LENS DEVELOPMENT; SIMIAN VIRUS-40 LARGE TUMOR ANTIGEN ID SACCHAROMYCES-CEREVISIAE; V(D)J RECOMBINATION; DNA RECOMBINATION; YEAST PLASMID; SYSTEM; GENE; BACTERIOPHAGE-P1; MECHANISM; SEQUENCES; GENOME AB An efficient and accurate method for controlled in vivo transgene modulation by site-directed recombination is described. Seven transgenic mouse founder lines were produced carrying the murine lens-specific alpha-A-crystallin promoter and the simian virus 40 large tumor-antigen gene sequence, separated by a 1.3-kilobase-pair Stop sequence that contains elements preventing expression of the large tumor-antigen gene and Cre recombinase recognition sites. Progeny from two of these lines were mated with transgenic mice expressing the Cre recombinase under control of either the murine alpha-A-crystallin promoter or the human cytomegalovirus promoter. All double-transgenic offspring developed lens tumors. Subsequent analysis confirmed that tumor formation resulted from large tumor-antigen activation via site-specific, Cre-mediated deletion of Stop sequences. C1 DUPONT MERCK PHARMACEUT INC,EXPTL STN E328,WILMINGTON,DE 19880. RP LAKSO, M (reprint author), NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892, USA. NR 32 TC 445 Z9 469 U1 0 U2 11 PU NATL ACAD PRESS 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 15 PY 1992 VL 89 IS 14 BP 6232 EP 6236 DI 10.1073/pnas.89.14.6232 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JD675 UT WOS:A1992JD67500002 PM 1631115 ER PT J AU LINNEKIN, D EVANS, GA DANDREA, A FARRAR, WL AF LINNEKIN, D EVANS, GA DANDREA, A FARRAR, WL TI ASSOCIATION OF THE ERYTHROPOIETIN RECEPTOR WITH PROTEIN TYROSINE KINASE-ACTIVITY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SIGNAL TRANSDUCTION; PROTEIN PHOSPHORYLATION ID COLONY-STIMULATING FACTOR; SIGNAL TRANSDUCTION; EXPRESSION CLONING; MOLECULAR-CLONING; CELL-LINES; PHOSPHORYLATION; INTERLEUKIN-3; GLYCOPROTEIN; GROWTH; SUPERFAMILY AB We have examined the signal transduction mechanism of the hematopoietic growth factor erythropoietin (Epo). Epo stimulation of Ba/F3 cells transfected with the Epo receptor resulted in increases in tyrosine phosphorylation of proteins of 97, 75, and 55 kDa. Epo-induced increases in tyrosine phosphorylation of a 97-kDa protein were also detected within the Epo receptor complex, suggesting that a protein tyrosine kinase is associated with the Epo receptor. Protein tyrosine kinase activity was found within the Epo receptor complex and modulation of this activity was observed after treatment of cells with Epo. Furthermore, constitutively high amounts of protein kinase activity were observed in Epo receptor complexes isolated from autonomously growing cells coexpressing the Epo receptor and the leukemogenic glycoprotein gp55. The dominant phosphotyrosylprotein found associated with the Epo receptor was 97 kDa. An Epo receptor-associated protein of identical molecular mass was also found to bind ATP, a characteristic critical for protein kinases. Collectively, these data demonstrate that the Epo receptor is associated with protein tyrosine kinase activity and further suggest that a 97-kDa phosphotyrosylprotein associated with the Epo receptor is a protein tyrosine kinase involved in Epo-mediated signal transduction. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,DYN CORP,PROGRAM RESOURCES INC,FREDERICK,MD 21701. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,DIV HEMATOL ONCOL,BOSTON,MA 02115. FU NCI NIH HHS [N01-CO-74102] NR 33 TC 61 Z9 61 U1 0 U2 0 PU NATL ACAD PRESS 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 15 PY 1992 VL 89 IS 14 BP 6237 EP 6241 DI 10.1073/pnas.89.14.6237 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JD675 UT WOS:A1992JD67500003 PM 1378622 ER PT J AU TAN, DP FERRANTE, J NAZARALI, A SHAO, XP KOZAK, CA GUO, V NIRENBERG, M AF TAN, DP FERRANTE, J NAZARALI, A SHAO, XP KOZAK, CA GUO, V NIRENBERG, M TI MURINE HOX-1.11 HOMEOBOX GENE STRUCTURE AND EXPRESSION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HOX-1.11 NUCLEOTIDE SEQUENCE; EMBRYONIC DEVELOPMENT ID DROSOPHILA; ORGANIZATION; SEGMENTATION; MUTATIONS; HINDBRAIN; PATTERNS; FAMILY; SITE AB The Hox-1.11 gene encodes a protein 372 amino acid residues long that contains a conserved pentapeptide, a homeodomain, and an acidic region. The amino acid sequence of the homeodomain of Hox-1.11 is identical to that of Hox-2.8, and the N-terminal and C-terminal regions of Hox-1.11 are similar to those of human HOX2H, which is the equivalent of murine Hox-2.8. The Hox-1.11 gene was shown to reside on murine chromosome 6, which contains the Hox-1 cluster of homeobox genes. One species of Hox-1.11 poly(A)+ RNA approximately 1.7 kb long was detected in mouse embryos, which is most abundant in 12-day-old embryos and progressively decreases during further embryonic development. The most anterior expression of Hox-1.11 poly(A)+ RNA in 12- to 14-day-old mouse embryos was shown by in situ hybridization to be in the mid and posterior hindbrain. Hox-1.11 poly(A)+ RNA also is expressed in the VII and VIII craniaL ganglia, spinal cord, spinal ganglia, larynx, lungs, vertebrae, sternum, and intestine. C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. RP TAN, DP (reprint author), NHLBI,BIOCHEM GENET LAB,BLDG 36,ROOM 1C06,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 27 TC 59 Z9 60 U1 0 U2 0 PU NATL ACAD PRESS 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 15 PY 1992 VL 89 IS 14 BP 6280 EP 6284 DI 10.1073/pnas.89.14.6280 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JD675 UT WOS:A1992JD67500012 PM 1352886 ER PT J AU QIAN, SW BURMESTER, JK MERWIN, JR MADRI, JA SPORN, MB ROBERTS, AB AF QIAN, SW BURMESTER, JK MERWIN, JR MADRI, JA SPORN, MB ROBERTS, AB TI IDENTIFICATION OF A STRUCTURAL DOMAIN THAT DISTINGUISHES THE ACTIONS OF THE TYPE-1 AND TYPE-2 ISOFORMS OF TRANSFORMING GROWTH-FACTOR-BETA ON ENDOTHELIAL-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GROWTH FACTORS; RECEPTORS; CHIMERAS ID TGF-BETA; 2 FORMS; RECEPTORS; BINDING; FACTOR-BETA-1; DETERMINANTS; PROTEINS; COMPLEX; CDNA AB A chimeric transforming growth factor-beta (TGF-beta) molecule has been synthesized to map the amino acids responsible for the substantially greater activity of TGF-beta-1 than TGF-beta-2 on growth and migration of endothelial cells. This chimera consists of a dimer of a monomeric unit composed of amino acids 1-39 of TGF-beta-2, 40-82 of TGF-beta-1, and 83-112 of TGF-beta-2. Structural identity of the purified recombinant protein has been confirmed by immunoblotting and NH2-terminal sequencing. The biological potency of the TGF-beta-2-1-2 chimera was equal to that of TGF-beta-1 in inhibition of growth of both fetal bovine heart endothelial cells and rat epididymal fat pad microvascular endothelial cells. Similarly, the TGF-beta-2-1-2 chimera was nearly equivalent to TGF-beta-1 and at least 10-fold more active than TGF-beta-2 in inhibiting migration of bovine aortic endothelial cells. These results identify the sequence between amino acids 40-82 as an important region within TGF-beta that functions to specify a TGF-beta-1- or TGF-beta-2-like activity. C1 NCI,CHEMOPREVENT LAB,BLDG 41,ROOM C629,BETHESDA,MD 20892. YALE UNIV,SCH MED,DEPT PATHOL,NEW HAVEN,CT 06510. FU NHLBI NIH HHS [R01-HL-28373] NR 35 TC 53 Z9 53 U1 0 U2 0 PU NATL ACAD PRESS 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 15 PY 1992 VL 89 IS 14 BP 6290 EP 6294 DI 10.1073/pnas.89.14.6290 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JD675 UT WOS:A1992JD67500014 PM 1631120 ER PT J AU SGANGA, MW AKSAMIT, RR CANTONI, GL BAUER, CE AF SGANGA, MW AKSAMIT, RR CANTONI, GL BAUER, CE TI MUTATIONAL AND NUCLEOTIDE-SEQUENCE ANALYSIS OF S-ADENOSYL-L-HOMOCYSTEINE HYDROLASE FROM RHODOBACTER-CAPSULATUS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE AHCY SEQUENCE; GENE EVOLUTION; BACTERIAL PHOTOSYNTHESIS ID AMINO-ACID SEQUENCE; ADENOSYLHOMOCYSTEINE HYDROLASE; RAT-LIVER; RHODOPSEUDOMONAS-CAPSULATA; ALCALIGENES-FAECALIS; ESCHERICHIA-COLI; CDNA SEQUENCE; BINDING; MUTAGENESIS; MECHANISM AB The genetic locus ahcY, encoding the enzyme S-adenosyl-L-homocysteine hydrolase (EC 3.3.1.1) from the bacterium Rhodobacter capsulatus, has been mapped by mutational analysis to within a cluster of genes involved in regulating the induction and maintenance of the bacterial photosynthetic apparatus. Sequence analysis demonstrates that ahcY encodes a 51-kDa polypeptide that displays 64% sequence identity to its human homolog. Insertion mutants in ahcY lack detectable S-adenosyl-L-homocysteine hydrolase activity and, as a consequence, S-adenosyl-L-homocysteine accumulates in the cells, resulting in a 16-fold decrease in the intracellular ratio of S-adenosyl-L-methionine to S-adenosyl-L-homocysteine as compared to wild-type cells. The ahcY disrupted strain fails to grow in minimal medium; however, growth is restored in minimal medium supplemented with methionine or homocysteine or in a complex medium, thereby indicating that the hydrolysis of S-adenosyl-L-homocysteine plays a key role in the metabolism of sulfur-containing amino acids. The ahcY mutant, when grown in supplemented medium, synthesizes significantly reduced levels of bacteriochlorophyll, indicating that modulation of the intracellular ratio of S-adenosyl-L-methionine to S-adenosyl-L-homocysteine may be an important factor in regulating bacteriochlorophyll biosynthesis. C1 INDIANA UNIV,DEPT BIOL,BLOOMINGTON,IN 47405. NIMH,GEN & COMPARAT BIOCHEM LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [R01 GM040941, GM40941-01] NR 46 TC 40 Z9 42 U1 0 U2 5 PU NATL ACAD PRESS 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 15 PY 1992 VL 89 IS 14 BP 6328 EP 6332 DI 10.1073/pnas.89.14.6328 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JD675 UT WOS:A1992JD67500022 PM 1631127 ER PT J AU WU, Y ZHOU, H DUESBERG, P AF WU, Y ZHOU, H DUESBERG, P TI UNMUTATED PROTO-SRC CODING REGION IS TUMORIGENIC IF EXPRESSED FROM THE PROMOTER OF ROUS-SARCOMA VIRUS - IMPLICATIONS FOR THE GENE-MUTATION HYPOTHESIS OF CANCER SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE RETROVIRAL ONCOGENICITY FROM TRANSCRIPTIONAL ACTIVATION; MUTATED GENES AND CANCER ID EMBRYO CELLS; RETROVIRAL PROMOTER; TRANSFORMING GENE; ONCOGENES; VARIANTS; INVITRO AB The transforming (onc) genes of oncogenic retroviruses share most or all of their coding sequences with normal cellular genes termed proto-onc genes. The viral genes differ from proto-onc genes in virus-specific promoters and in various point mutations and substitutions of cell-derived coding regions. In view of the structural similarities between viral oncogenes and cellular proto-onc genes, the hypothesis has been advanced that proto-onc genes become cellular cancer genes if they have suffered mutations. Indeed, point mutations and substitutions have been observed in the proto-onc genes of some cancers. However, the hypothesis has been difficult to prove because mutated proto-onc genes from tumors do not transform diploid cells. Moreover, owing to the popularity of this hypothesis, even viral oncogenes are thought to derive transforming function from mutations of this cell-derived coding region. A competing hypothesis proposes that enhanced expression from retroviral promoters is necessary and sufficient for oncogenic function of proto-onc genes. To distinguish between these hypotheses we have tested tumorigenicity of RpSV, a synthetic retrovirus with the normal proto-src coding region in a vector derived from Rous sarcoma virus (RSV). In addition, we have tested the role of RSV-specific src point mutations on the tumorigenicity of RpSV. It was found that RpSV with an unmutated proto-src coding region is tumorigenic in chickens and that tumorigenicity is enhanced by RSV-specific src point mutations. It is concluded that retroviral promoters are essential for the transforming function of viral oncogenes and that certain point mutations merely supplement their transforming function. Thus retroviral onc genes are not models for the hypothesis that mutated, but transcriptionally normal, proto-onc genes of certain tumors are cancer genes. C1 UNIV CALIF BERKELEY,DEPT MOLEC & CELL BIOL,BERKELEY,CA 94720. NCI,FREDERICK CANC RES FACIL,MOLEC ONCOL LAB,FREDERICK,MD 21701. FU NCI NIH HHS [5-R35-CA39915-07] NR 49 TC 10 Z9 10 U1 0 U2 0 PU NATL ACAD PRESS 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 15 PY 1992 VL 89 IS 14 BP 6393 EP 6397 DI 10.1073/pnas.89.14.6393 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JD675 UT WOS:A1992JD67500035 PM 1321438 ER PT J AU DONALDSON, JG CASSEL, D KAHN, RA KLAUSNER, RD AF DONALDSON, JG CASSEL, D KAHN, RA KLAUSNER, RD TI ADP-RIBOSYLATION FACTOR, A SMALL GTP-BINDING PROTEIN, IS REQUIRED FOR BINDING OF THE COATOMER PROTEIN BETA-COP TO GOLGI MEMBRANES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BREFELDIN-A; TRANSPORT; STACK; COFACTOR; PATHWAY; CELLS; TOXIN; ER AB The coatomer is a cytosolic protein complex that reversibly associates with Golgi membranes and is implicated in modulating Golgi membrane transport. The association of beta-COP, a component of coatomer, with Golgi membranes is enhanced by guanosine 5'-[gamma-thio]triphosphate (GTP[gamma-S]), a nonhydrolyzable analogue of GTP, and by a mixture of aluminum and fluoride ions (Al/F). Here we show that the ADP-ribosylation factor (ARF) is required for the binding of beta-COP. Thus, beta-COP contained in a coatomer fraction that has been resolved from ARF does not bind to Golgi membranes, whereas binding can be reconstituted by the addition of recombinant ARF. Furthermore, an N-terminal peptide of ARF, which blocks ARF binding to Golgi membranes, inhibits GTP[gamma-S]- as well as the Al/F-enhanced binding of beta-COP. We show that Golgi coat protein binding involves a sequential reaction where an initial interaction of ARF and GTP[gamma-S] with the membrane allows subsequent binding of beta-COP to take place in the absence of free ARF and GTP[gamma-S]. The fungal metabolite brefeldin A, which is known to prevent the association of coat proteins with Golgi membrane, is shown to exert this effect by interfering with the initial ARF-membrane interaction step. C1 NCI,DIV CANC TREATMENT,BIOL CHEM LAB,BETHESDA,MD 20892. RP DONALDSON, JG (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. NR 30 TC 404 Z9 408 U1 1 U2 3 PU NATL ACAD PRESS 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 15 PY 1992 VL 89 IS 14 BP 6408 EP 6412 DI 10.1073/pnas.89.14.6408 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JD675 UT WOS:A1992JD67500038 PM 1631136 ER PT J AU LEMARCHAND, P JAFFE, HA DANEL, C CID, MC KLEINMAN, HK STRATFORDPERRICAUDET, LD PERRICAUDET, M PAVIRANI, A LECOCQ, JP CRYSTAL, RG AF LEMARCHAND, P JAFFE, HA DANEL, C CID, MC KLEINMAN, HK STRATFORDPERRICAUDET, LD PERRICAUDET, M PAVIRANI, A LECOCQ, JP CRYSTAL, RG TI ADENOVIRUS-MEDIATED TRANSFER OF A RECOMBINANT HUMAN ALPHA-1-ANTITRYPSIN CDNA TO HUMAN ENDOTHELIAL-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GENE-EXPRESSION INVIVO; RETROVIRAL VECTORS; ARTERIAL-WALL; INFECTION; DEFICIENCY; INVITRO AB To evaluate the feasibility of using a replication-deficient recombinant adenovirus to transfer human genes to the human endothelium, human umbilical vein endothelial cells were infected in vitro with adenovirus vectors containing the lacZ gene or a human alpha-1-antitrypsin (alpha-1AT) cDNA. After in vitro infection with the lacZ adenovirus vector, cultured endothelial cells expressed beta-galactosidase. In parallel studies with the alpha-1AT adenovirus vector, infected cells expressed human alpha-1AT transcripts, as evidenced by in situ hybridization and Northern analysis, and de novo synthesized and secreted glycosylated, functional alpha-1AT within 6 hr of infection, as shown by [S-35]methionine labeling and immunoprecipitation. Quantification of the culture supernatants demonstrated 0.3-0.6-mu-g of human alpha-1AT secreted per 10(6) cells in 24 hr, for at least 14 days after adenovirus vector infection. To demonstrate the feasibility of direct transfer of genes into endothelial cells in human blood vessels, lacZ or alpha-1AT adenovirus vectors were placed in the lumen of intact human umbilical veins ex vivo. Histologic evaluation of the veins after 24 hr demonstrated transfer and expression of the lacZ gene specifically to the endothelium. Alpha-1AT adenovirus infection resulted both in expression of alpha-1AT transcripts in the endothelium and in de novo synthesis and secretion of alpha-1AT. Quantification of alpha-1AT in the vein perfusates showed average levels of 13-mu-g/ml after 24 hr. These observations strongly support the feasibility of in vivo human gene transfer to the endothelium mediated by replication-deficient adenovirus vectors. C1 NHLBI,PULM BRANCH,BETHESDA,MD 20892. TRANSGENE SA,STRASBOURG,FRANCE. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. INST GUSTAVE ROUSSY,CNRS,UA 1301,F-94805 VILLEJUIF,FRANCE. RI lemarchand, patricia/C-3247-2011; OI Cid Xutgla, Maria Cinta/0000-0002-4730-0938 NR 38 TC 180 Z9 182 U1 0 U2 2 PU NATL ACAD PRESS 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 15 PY 1992 VL 89 IS 14 BP 6482 EP 6486 DI 10.1073/pnas.89.14.6482 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JD675 UT WOS:A1992JD67500053 PM 1631146 ER PT J AU SUN, Y HEGAMYER, G CHENG, YJ HILDESHEIM, A CHEN, JY CHEN, IH CAO, Y YAO, KT COLBURN, NH AF SUN, Y HEGAMYER, G CHENG, YJ HILDESHEIM, A CHEN, JY CHEN, IH CAO, Y YAO, KT COLBURN, NH TI AN INFREQUENT POINT MUTATION OF THE P53 GENE IN HUMAN NASOPHARYNGEAL CARCINOMA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TUMOR-SUPPRESSOR GENE; NASOPHARYNGEAL CARCINOGENESIS; PCR ID EPSTEIN-BARR VIRUS; CELL LINES HNE-1; TUMOR-ANTIGEN; NEOPLASTIC TRANSFORMATION; MUTANT P53; FREQUENT; PROTEIN; CANCER; DNA; SUPPRESSOR AB Point mutations in the p53 gene have been detected in a variety of human cancers; the mutations are clustered in four "hot-spots" located in the coding region of exons 5, 7, and 8, which coincide with the four most highly conserved regions of the gene. We report the finding of a heterozygous G --> C mutation at codon 280 (exon 8), position 2, of the p53 gene in a nasopharyngeal carcinoma (NPC) cell line, originating from Guangdong, a province in the People's Republic of China that leads the world in NPC incidence. A survey of nasopharyngeal tissues and NPC biopsies revealed that 1 out of 12 NPC samples from Hunan, another province in the People's Republic of China with high NPC incidence, had the same heterozygous mutation at codon 280 of p53, and none of 10 biopsies from Taiwan showed a mutation within exons 5-8 of the p53 gene. No other alteration of gene structure, including gross rearrangement or loss of heterozygosity or abnormality of gene expression was detected in NPC cell lines or NPC biopsies. We conclude from this study that mutational or other alterations of the p53 gene are not common in nasopharyngeal carcinogenesis and that a codon-280 mutation of p53 may be involved in <10% of NPC cases. This result contrasts with the relatively high frequency of p53 mutations associated with several other human carcinomas and suggests the importance of other genes in NPC genesis. C1 NCI,FREDERICK CANC RES DEV CTR,VIRAL CARCINOGENESIS LAB,CELL BIOL SECT,BETHESDA,MD 20892. NATL TAIWAN UNIV,COLL MED,INST PUBL HLTH,TAIPEI,TAIWAN. NATL TAIWAN UNIV,COLL MED,INST MICROBIOL,TAIPEI,TAIWAN. NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. MACKAY HOSP,DEPT OTOLARYNGOL,TAIPEI,TAIWAN. HUNAN MED UNIV,HUNAN CANC INST,HUNAN,PEOPLES R CHINA. RP SUN, Y (reprint author), NCI,FREDERICK CANC RES DEV CTR,DYNCORP,PROGRAM RESOURCES INC,BETHESDA,MD 20892, USA. RI Chen, Jen-Yang/D-2085-2010 FU NCI NIH HHS [N01-CO-74102] NR 48 TC 133 Z9 144 U1 0 U2 2 PU NATL ACAD PRESS 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 15 PY 1992 VL 89 IS 14 BP 6516 EP 6520 DI 10.1073/pnas.89.14.6516 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JD675 UT WOS:A1992JD67500060 PM 1631151 ER PT J AU MARINI, AM PAUL, SM AF MARINI, AM PAUL, SM TI N-METHYL-D-ASPARTATE RECEPTOR-MEDIATED NEUROPROTECTION IN CEREBELLAR GRANULE CELLS REQUIRES NEW RNA AND PROTEIN-SYNTHESIS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE 1-METHYL-4-PHENYLPYRIDINIUM ION AND GLUTAMATE TOXICITY; NEUROPROTECTIVE PROTEIN(S) ID KAINIC ACID; NEUROTOXICITY; GLUTAMATE; CULTURE; EXCITOTOXICITY; LOCALIZATION; STIMULATION; DISEASE; RELEASE AB Cerebellar granule cells are susceptible to the excitotoxin glutamate, which acts at N-methyl-D-aspartate (NMDA) receptors, as well as the neurotoxin 1-methyl-4-phenylpyridinium ion (MPP+), the active cytotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Paradoxically, preincubation of cultured cerebellar granule cells with low concentrations of NMDA or glutamate markedly antagonizes the neurotoxicity resulting from subsequent exposure to toxic concentrations of either MPP+ or glutamate. The neuroprotective effects of NMDA and glutamate against MPP+ toxicity are observed at agonist concentrations as low as 1-mu-M, are blocked by specific NMDA receptor antagonists, and require at least 30 min to develop fully. Moreover, NMDA receptor-mediated neuroprotection is prevented by the RNA synthesis inhibitor actinomycin D or the protein synthesis inhibitor cycloheximide. Thus, in cerebellar granule cells activation of NMDA receptors by glutamate can result in either neurotoxicity or neuroprotection, depending on the apparent degree of receptor stimulation. NMDA receptor-mediated neuroprotection requires new RNA and protein synthesis and therefore appears to be mediated by the expression of a neuroprotective protein(s). These data demonstrate the presence of an active NMDA receptor-mediated and transcriptionally directed neuroprotective mechanism in cerebellar granule cells. C1 NIMH,CLIN NEUROSCI BRANCH,MOLEC PHARMACOL SECT,BETHESDA,MD 20892. NR 26 TC 159 Z9 159 U1 0 U2 0 PU NATL ACAD PRESS 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 15 PY 1992 VL 89 IS 14 BP 6555 EP 6559 DI 10.1073/pnas.89.14.6555 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JD675 UT WOS:A1992JD67500068 PM 1385875 ER PT J AU ZEUZEM, S FEICK, P ZIMMERMANN, P HAASE, W KAHN, RA SCHULZ, I AF ZEUZEM, S FEICK, P ZIMMERMANN, P HAASE, W KAHN, RA SCHULZ, I TI INTRAVESICULAR ACIDIFICATION CORRELATES WITH BINDING OF ADP-RIBOSYLATION FACTOR TO MICROSOMAL-MEMBRANES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE LOW MOLECULAR WEIGHT GTP-BINDING PROTEIN; VACUOLAR-TYPE H+-ATPASE; BAFILOMYCIN ID PANCREATIC ACINAR-CELLS; PROTEINS; SECRETION; YEAST; VESICLES; ATPASES AB The ADP-ribosylation factor (ARF), a highly conserved low molecular weight GTP-binding protein, has been implicated to function in intracellular protein transport to and within the Golgi complex. In pancreatic acinar cells the ARF is confined to the cytoplasmic faces of trans-Golgi stack membranes, a compartment known to maintain a low intravesicular pH, which is established by a chloride-dependent MgATP-driven proton pump. The present study shows that MgATP (2 mM), but neither adenosine 5'-[gamma-thio]triphosphate in the presence of Mg2+ nor ATP in the absence of Mg2+, increases transfer of ARF from the surrounding medium into the vesicle membranes. The specific vacuolar-type proton pump inhibitor bafilomycin B1 (10 nM), the protonophore carbonylcyanide m-chlorophenylhydrazone (10-mu-M), and replacement of chloride in the incubation buffer by acetate or nitrate resulted in an almost complete inhibition of the MgATP-dependent association of ARF to the vesicle membranes. The results demonstrate that redistribution of ARF to the vesicle membrane correlates with the intravesicular pH established by a vacuolar-type H+-ATPase. The intravesicular pH appears to be one mechanism by which certain low molecular weight GTP-binding proteins become relocated from the cytosol to their specific membrane vesicles. C1 MAX PLANCK INST BIOPHYS,W-6000 FRANKFURT,GERMANY. NCI,DIV CANC TREATMENT,BIOL CHEM LAB,BETHESDA,MD 20892. NR 19 TC 87 Z9 87 U1 1 U2 1 PU NATL ACAD PRESS 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 15 PY 1992 VL 89 IS 14 BP 6619 EP 6623 DI 10.1073/pnas.89.14.6619 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JD675 UT WOS:A1992JD67500081 PM 1385876 ER PT J AU SMYTH, MS FORD, H BURKE, TR AF SMYTH, MS FORD, H BURKE, TR TI A GENERAL-METHOD FOR THE PREPARATION OF BENZYLIC ALPHA,ALPHA-DIFLUOROPHOSPHONIC ACIDS - NONHYDROLYZABLE MIMETICS OF PHOSPHOTYROSINE SO TETRAHEDRON LETTERS LA English DT Article ID TYROSINE KINASE; ANALOGS AB Methodology is presented for the preparation of heretofore unreported benzylic alpha,alpha-difluorophosphonic acids. Oxidation of benzylic alpha-hydroxyphosphonates using MnO2 provided a new route for the synthesis of benzylic alpha-oxophosphonate, which were then fluorinated using DAST. Hydrolysis of ester protecting groups yielded alpha,alpha-difluorophosphonic acids. These represent non-hydrolyzable mimetics of arylphosphates which could be of value in the study of cellular phosphotyrosine-utilizing signal transduction pathways. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. RI Burke, Terrence/N-2601-2014 NR 19 TC 115 Z9 118 U1 0 U2 4 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 JUL 14 PY 1992 VL 33 IS 29 BP 4137 EP 4140 DI 10.1016/S0040-4039(00)74672-7 PG 4 WC Chemistry, Organic SC Chemistry GA JD930 UT WOS:A1992JD93000012 ER PT J AU ILYINA, TV KOONIN, EV AF ILYINA, TV KOONIN, EV TI CONSERVED SEQUENCE MOTIFS IN THE INITIATOR PROTEINS FOR ROLLING CIRCLE DNA-REPLICATION ENCODED BY DIVERSE REPLICONS FROM EUBACTERIA, EUKARYOTES AND ARCHAEBACTERIA SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SINGLE-STRANDED-DNA; PHAGE-PLASMID HYBRID; NUCLEOTIDE-SEQUENCE; ESCHERICHIA-COLI; VIRAL-DNA; REGIONS; ORGANIZATION; CLEAVAGE; GENOME; VIRUS AB An amino acid motif was identified that consists of the sequence HisHydrHisHydrHydrHydr (Hydr-bulky hydrophobic residue) and is conserved in two vast classes of proteins, one of which is involved in initiation and termination of rolling circle DNA replication, or RCR (Rep proteins), and the other in mobilization (conjugal transfer) of plasmid DNA (Mob proteins). Based on analogies with metalloenzymes, it is hypothesized that the two conserved His residues in this motif may be involved in metal ion coordination required for the activity of the Rep and Mob proteins. Rep proteins contained two additional conserved motifs, one of which was located upstream, and the other downstream from the 'two His' motif. The C-terminal motif encompassed the Tyr residue(s) forming the covalent link with nicked DNA. Mob proteins were characterized by the opposite orientation of the conserved motifs, with the (putative) DNA-linking Tyr being located near their N-termini. Both Rep and Mob protein classes further split into several distinct families. Although it was not possible to find a motif or pattern that would be unique for the entire Rep or Mob class, unique patterns were derived for large subsets of the proteins of each class. These observations allowed the prediction of the amino acid residues involved in DNA nicking, which is required for the initiation of RCR or conjugal transfer of single-stranded (ss) DNA, in Rep and Mob proteins encoded by a number of replicons of highly diverse size, structure and origin. It is conjectured that recombination has played a major part in the dissemination of genes encoding related Rep or Mob proteins among the replicons exploiting RCR. It is speculated that the eucaryotic small ssDNA replicons encoding proteins with the conserved RCR motifs and replicating via RCR-related mechanisms, such as geminiviruses and parvoviruses, may have evolved from eubacterial replicons. C1 NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,8600 ROCKVILLE PIKE,BETHESDA,MD 20894. ACAD SCI,INST MICROBIOL,MOSCOW 117811,USSR. NR 47 TC 428 Z9 438 U1 1 U2 20 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 JUL 11 PY 1992 VL 20 IS 13 BP 3279 EP 3285 DI 10.1093/nar/20.13.3279 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JE818 UT WOS:A1992JE81800001 PM 1630899 ER PT J AU RODRIGUEZ, IR CHADER, GJ AF RODRIGUEZ, IR CHADER, GJ TI A NOVEL METHOD FOR THE ISOLATION OF TISSUE-SPECIFIC GENES SO NUCLEIC ACIDS RESEARCH LA English DT Note ID CDNA RP RODRIGUEZ, IR (reprint author), NEI,BLDG 6,ROOM 307,BETHESDA,MD 20892, USA. NR 3 TC 35 Z9 37 U1 2 U2 5 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 JUL 11 PY 1992 VL 20 IS 13 BP 3528 EP 3528 DI 10.1093/nar/20.13.3528 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JE818 UT WOS:A1992JE81800051 PM 1630937 ER PT J AU LIPSKA, BK JASKIW, GE CHRAPUSTA, S KAROUM, F WEINBERGER, DR AF LIPSKA, BK JASKIW, GE CHRAPUSTA, S KAROUM, F WEINBERGER, DR TI IBOTENIC ACID LESION OF THE VENTRAL HIPPOCAMPUS DIFFERENTIALLY AFFECTS DOPAMINE AND ITS METABOLITES IN THE NUCLEUS-ACCUMBENS AND PREFRONTAL CORTEX IN THE RAT SO BRAIN RESEARCH LA English DT Article DE HIPPOCAMPUS; DOPAMINE; IBOTENIC ACID; AMPHETAMINE; LOCOMOTION; NUCLEUS ACCUMBENS; PREFRONTAL CORTEX ID BIOCHEMICAL-EVIDENCE; DIRECT PROJECTION; OPPOSITE CHANGES; BASAL GANGLIA; AMMONS HORN; KAINIC ACID; BRAIN; AMPHETAMINE; SCHIZOPHRENIA; NEURONS AB To determine the influence of neurons of the ventral hippocampus on dopamine (DA) turnover in other limbic areas, spontaneous and amphetamine-induced locomotion as well as DA and its metabolites were assayed in nucleus accumbens, medial prefrontal cortex and anteromedial striatum, 14 and 28 days after bilateral ibotenic acid (IA) or sham lesions of the ventral hippocampus in the rat. Spontaneous locomotion was increased 28 days postoperatively, while D-amphetamine induced locomotion was augmented both 14 and 28 days postoperatively in IA lesioned animals. DA levels in the nucleus accumbens were decreased on the 14th, but increased on the 28th day after the lesion. Dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and the DOPAC/DA ratio in the medial prefrontal cortex (MPFC) were reduced 28 days postoperatively. Moreover, there was a significant negative correlation between the DOPAC/DA ratio in the MPFC and DA levels in the nucleus accumbens at this time point. These data indicate that a lesion of the ventral hippocampus can produce differential changes in cortical and limbic DA activity. Implications for an animal model of schizophrenia are considered. C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,INTRAMURAL RES PROGRAM,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. RP LIPSKA, BK (reprint author), ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,RM 500,WASHINGTON,DC 20032, USA. RI Lipska, Barbara/E-4569-2017 NR 57 TC 153 Z9 153 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 JUL 10 PY 1992 VL 585 IS 1-2 BP 1 EP 6 DI 10.1016/0006-8993(92)91184-G PG 6 WC Neurosciences SC Neurosciences & Neurology GA JH130 UT WOS:A1992JH13000001 PM 1511295 ER PT J AU BABILA, T SCHAAD, NC SIMONDS, WF SHINOHARA, T KLEIN, DC AF BABILA, T SCHAAD, NC SIMONDS, WF SHINOHARA, T KLEIN, DC TI DEVELOPMENT OF MEKA (PHOSDUCIN), G-BETA, G-GAMMA AND S-ANTIGEN IN THE RAT PINEAL-GLAND AND RETINA SO BRAIN RESEARCH LA English DT Article DE PINEAL; RETINA; G-PROTEIN; MEKA; S-ANTIGEN; TRANSDUCIN ID GTP-BINDING PROTEINS; N-ACETYLTRANSFERASE; AMINO-ACID; PHOTORECEPTOR; CELLS; CDNA; TRANSDUCIN; SUBUNIT; BOVINE; PHOSPHORYLATION AB Pinealocytes and retinal photoreceptor cells contain an unusual cytoplasmic complex composed of the G-beta-gamma dimer of GTP-binding regulatory proteins (G-proteins) tightly bound to an acidic 33 kDa phosphoprotein termed MEKA or phosducin; MEKA is a substrate of cyclic AMP-dependent protein kinase. This study characterized the developmental appearance of these and two related proteins, G-gamma and S-antigen, in pineal and retinal tissue. MEKA was absent in the pineal gland prior to birth, at a time when it was possible to detect G-beta in pineal cytoplasm, indicating that the appearance of G-beta in the cytoplasm precedes that of MEKA and does not appear to require the presence of MEKA. The absence of MEKA at this time indicates that the cyclic AMP stimulation of pineal serotonin N-acetyltransferase activity is not mediated by MEKA, which has been considered as a possible role of MEKA. After postnatal day 7, pineal MEKA and cytoplasmic G-beta increased in a parallel manner, with peak values occurring at about postnatal day 21. Thereafter, both proteins in the pineal gland decreased in a parallel fashion to 10 and 35% of their peak values, respectively; in contrast, the cytoplasmic protein S-antigen and membrane associated G-beta remained at maximal levels after this time. Whereas both MEKA and G-beta decreased late in development in the pineal gland, these proteins either increased or remained constant in the retina. These tissue-specific patterns were found to differ from those of another cytosolic protein found exclusively in the pineal gland and retina, S-antigen, which remained constant after day 21 in the pineal gland but decreased in the retina late in life. C1 NICHHD,DEV NEUROBIOL LAB,NEUROENDOCRINOL SECT,BLDG 36,ROOM 4A07,BETHESDA,MD 20892. NIDDKD,METAB DIS BRANCH,MOLEC PATHOPHYSIOL SECT,BETHESDA,MD 20892. NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. OI Shinohara, Toshimichi/0000-0002-7197-9039 NR 38 TC 22 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 10 PY 1992 VL 585 IS 1-2 BP 141 EP 148 DI 10.1016/0006-8993(92)91199-O PG 8 WC Neurosciences SC Neurosciences & Neurology GA JH130 UT WOS:A1992JH13000016 PM 1511297 ER PT J AU THOMAS, DA WILLIAMS, GM IWATA, K KENSHALO, DR DUBNER, R AF THOMAS, DA WILLIAMS, GM IWATA, K KENSHALO, DR DUBNER, R TI EFFECTS OF CENTRAL ADMINISTRATION OF OPIOIDS ON FACIAL SCRATCHING IN MONKEYS SO BRAIN RESEARCH LA English DT Note DE OPIOID; PRURITUS; BRAIN-STEM; BEHAVIOR; ITCH; MONKEY ID MEDULLARY DORSAL HORN; OBSTETRIC ANALGESIA; PERCEIVED INTENSITY; OPIATE RECEPTORS; NOXIOUS HEAT; MORPHINE; AGONIST; RAT AB Epidural and intrathecal administration of opioids to humans can produce facial pruritus and scratching that is naloxone reversible. It has been proposed that opioids may act at the level of the medulla to produce facial pruritus and associated scratching behavior. We investigated the effects of mu, delta and kappa-opioid-receptor agonists microinjected unilaterally into the medullary dorsal horn (MDH) on facial scratching in cynomologus monkeys. The selective mu-opioid-receptor agonist, DAMGO (3.1-25.0 ng) produced large dose-dependent, naloxone-reversible increases in facial scratches. The selective delta-opioid-receptor agonist, DPDPE (1.0-5.0-mu-g) and the selective kappa-opioid-receptor agonist, U-50,488H (0.1-5.0-mu-g) did not produce significant increases in facial scratching behavior. We conclude that the MDH is a site where DAMGO, a mu-opioid-receptor agonist, can act to produce facial scratching in monkeys, and that the MDH is likely the site where centrally administered opioids act to produce facial pruritus in humans. RP THOMAS, DA (reprint author), NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BLDG 30,ROOM B20,BETHESDA,MD 20892, USA. NR 21 TC 60 Z9 61 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 JUL 10 PY 1992 VL 585 IS 1-2 BP 315 EP 317 DI 10.1016/0006-8993(92)91227-6 PG 3 WC Neurosciences SC Neurosciences & Neurology GA JH130 UT WOS:A1992JH13000044 PM 1511314 ER PT J AU TAYLOR, TC KAHN, RA MELANCON, P AF TAYLOR, TC KAHN, RA MELANCON, P TI 2 DISTINCT MEMBERS OF THE ADP-RIBOSYLATION FACTOR FAMILY OF GTP-BINDING PROTEINS REGULATE CELL-FREE INTRA-GOLGI TRANSPORT SO CELL LA English DT Article ID ADENYLATE-CYCLASE; VESICULAR TRANSPORT; MOLECULAR-WEIGHT; BOVINE BRAIN; YEAST; PURIFICATION; SECRETION; COMPARTMENTS; LOCALIZATION; EXPRESSION AB We have used an intra-Golgi transport assay to identify GTP-binding proteins involved in regulation of protein traffic. Two soluble proteins of 20 kd were purified by their ability to mediate GTP-gamma-S-dependent inhibition of transport. These GTP-dependent Golgi binding factors, or GGBFs, exhibit a 3-fold difference in activity and are differentiated by their hydrophobicity, isoelectric points, and apparent size. Removal of 80% of GGBFs from cytosol abolishes GTP-gamma-S sensitivity but does not affect inhibition by aluminum fluoride. We demonstrate that GGBFs are members of the ADP-ribosylation factor (ARF) family. Recombinant ARF1 exhibits GGBF activity and myristoylation is required. The distinct biochemical properties of GGBFs indicate that members of the ARF family may have related but distinct functions in intracellular transport. C1 NCI, DIV CANC TREATMENT, DEV THERAPEUT PROGRAM, BIOL CHEM LAB, BETHESDA, MD 20892 USA. RP UNIV COLORADO, DEPT CHEM & BIOCHEM, BOULDER, CO 80309 USA. FU NIGMS NIH HHS [GM43378] NR 54 TC 118 Z9 118 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD JUL 10 PY 1992 VL 70 IS 1 BP 69 EP 79 DI 10.1016/0092-8674(92)90534-J PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JC957 UT WOS:A1992JC95700009 PM 1623523 ER PT J AU ROSNER, MH VIGANO, MA RIGBY, PWJ ARNHEITER, H STAUDT, LM AF ROSNER, MH VIGANO, MA RIGBY, PWJ ARNHEITER, H STAUDT, LM TI OCT-3 AND MAMMALIAN DEVELOPMENT - CORRECTION OF DISCUSSION SO SCIENCE LA English DT Letter C1 UNIV MILAN,DEPT PHARMACOL CHEMOTHERAPY & MED TOXICOL,I-20122 MILAN,ITALY. NATL INST MED RES,EUKARYOT MOLEC GENET LAB,LONDON NW7 1AA,ENGLAND. NINCDS,VIRAL & MOLEC PATHOGENESIS LAB,BETHESDA,MD 20892. NCI,METAB BRANCH,BETHESDA,MD 20892. RP ROSNER, MH (reprint author), HARVARD UNIV,SCH MED,180 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 10 PY 1992 VL 257 IS 5067 BP 147 EP 147 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JC585 UT WOS:A1992JC58500008 PM 1631538 ER PT J AU SAFI, N KANTOR, RRS ATKINSON, B MORATZ, C WILT, AR PANCAKE, S REBA, R MATHIESON, BJ DESGREZ, A AF SAFI, N KANTOR, RRS ATKINSON, B MORATZ, C WILT, AR PANCAKE, S REBA, R MATHIESON, BJ DESGREZ, A TI 2 ANTIGENS DETECTED ON HUMAN OCULAR MELANOMAS WITH THE MOUSE MONOCLONAL-ANTIBODIES 2/10SN AND 10/12SN SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID TISSUE DISTRIBUTION; GLYCOPROTEIN; HETEROGENEITY; CELLS; P97 AB Seven human ocular melanoma cell lines were established in vitro and 3 of these, GU-4, LLN-40 and its subline C17-11, were characterized. Mice were immunized with these ocular melanoma cell lines, and 2 hybridomas producing monoclonal IgG1 antibodies (MAb) were produced. MAb 2/10SN recognizes a 44-kDa monomeric protein, whereas MAb 10/12SN reacts with an 83/65-kDa heterodimeric protein. These melanoma-associated antigens (MAA) are detected at high concentrations in the cytoplasm of ocular melanoma cells. However, cell-surface labelling techniques suggest that these MAA are also associated with the cell-surface membrane. These 2 ocular MAA are also expressed by several skin melanoma cell lines. Immunohistochemical studies have localized these antigens to ocular and skin melanomas, to sweat ducts and basal squamous cells in normal skin, with limited expression in several other normal tissues and some carcinomas. Biodistribution studies in nude mice with human ocular melanomas have demonstrated good localization of I-125-labeled MAb 2/10SN at the tumor sites. Therefore, these 2 MAbs, 2/10SN and 10/12SN, recognize MAA which appear to be unique and may prove useful for imaging purposes. C1 HOP BICETRE,DEPT MED NUCL,F-94000 LE KREMLIN BICETR,FRANCE. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,FREDERICK,MD 21701. HOSP UNIV PENN,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BRMP,FREDERICK,MD 21701. RP SAFI, N (reprint author), GEORGE WASHINGTON UNIV,MED CTR,DEPT RADIOL,DIV NUCL MED,WASHINGTON,DC 20037, USA. FU NCI NIH HHS [N01-CA-74102] NR 31 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 9 PY 1992 VL 51 IS 5 BP 718 EP 726 DI 10.1002/ijc.2910510510 PG 9 WC Oncology SC Oncology GA JD225 UT WOS:A1992JD22500009 PM 1612780 ER PT J AU FRIDMAN, R SWEENEY, TM ZAIN, M MARTIN, GR KLEINMAN, HK AF FRIDMAN, R SWEENEY, TM ZAIN, M MARTIN, GR KLEINMAN, HK TI MALIGNANT TRANSFORMATION OF NIH-3T3 CELLS AFTER SUBCUTANEOUS COINJECTION WITH A RECONSTITUTED BASEMENT-MEMBRANE (MATRIGEL) SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID CAPILLARY-LIKE STRUCTURES; HUMAN-ENDOTHELIAL CELLS; METASTATIC PHENOTYPE; LAMININ; ONCOGENE; INVITRO; DIFFERENTIATION; GROWTH AB NIH-3T3 cells are non-tumorigenic when injected into athymic mice. If these cells are mixed with an extract of basement-membrane proteins (matrigel) and injected s.c., they form locally invasive and highly vascularized tumors. Cells cultured from the NIH-3T3-matrigel-induced tumors showed a transformed phenotype and lacked contact inhibition. When cultured in a gel of matrigel, they proliferated and formed branched and invasive colonies. In contrast, the parental NIH-3T3 cells cultured on matrigel remained as cell aggregates and were not invasive. I.V. injections of the tumor-derived NIH-3T3 cells produced many colonies on the surface of the lungs, whereas the parental NIH-3T3 cells were not metastatic. Zymographic analysis of the conditioned media obtained from both the tumor-derived and parental NIH-3T3 cells demonstrated higher amounts of the 72-kDa gelatinase (type-IV collagenase) enzyme in the tumor-derived cells. Also, tumor-derived NIH-3T3 cells, but not parental NIH-3T3 cells, secreted the 92-kDa type-IV collagenase. These studies suggest that the interaction of pre-malignant NIH-3T3 cells with extracellular matrix components may contribute to the process of tumor progression. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NIA,BALTIMORE,MD 21224. RP FRIDMAN, R (reprint author), MOLEC ONCOL INC,19 FIRSTFIELD RD,GAITHERSBURG,MD 20878, USA. NR 25 TC 42 Z9 44 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 9 PY 1992 VL 51 IS 5 BP 740 EP 744 DI 10.1002/ijc.2910510513 PG 5 WC Oncology SC Oncology GA JD225 UT WOS:A1992JD22500012 PM 1319408 ER PT J AU SCHWARTZ, MS SMITH, GH MEDINA, D AF SCHWARTZ, MS SMITH, GH MEDINA, D TI THE EFFECT OF PARITY, TUMOR LATENCY AND TRANSPLANTATION ON THE ACTIVATION OF INT LOCI IN MMTV-INDUCED, TRANSPLANTED C3H MAMMARY PRE-NEOPLASIAS AND THEIR TUMORS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID NUCLEOTIDE-SEQUENCE; MOUSE; EXPRESSION; VIRUS; GENE; TUMORIGENESIS; ONCOGENES; INSERTION; MICE; P53 AB Mouse mammary tumor virus (MMTV) infection of mammary glands results in proviral insertion into host DNA and activation of cellular genes. Clonal expansion of cells bearing insertional mutations results in hyperplastic alveolar nodules (HAN) and tumors. HAN, transplanted into epithelium-cleared mammary fat pads, form hyperplastic alveolar outgrowths (HOGs). Previous work indicates the commonly MMTV-activated genes wnt-1 and int-2 are rarely affected in HOGs and HOG-derived tumors. To determine the basis of the dichotomy between the frequency of wnt/int gene activation in HOG-derived tumors and tumors from breeders of the identical inbred mouse strain, we compared the activation of wnt-1, int-2 and int-3 in tumors from virgin and breeding C3H mice, in consecutive primary tumors arising in individual C3H breeders and in C3H HOGs at early passages. Activation of wnt-1 or int-2 was rare in HOG-derived tumors (6% and 0%) compared with primary tumors in breeders (52% and 14%). int-3 was never found to be activated. wnt-1 was activated in the same percentage of primary tumors from virgins as from breeders. int-2 was activated only in tumors from breeders. wnt-1 activation also did not correlate with shorter tumor latency in multiple tumors from individual breeders. wnt-1 RNA was not detected in HOGs at early transplant generations, however, low levels of wnt-1 RNA were variably found in the epithelium of virgin mammary glands. We cannot explain why C3H HOGs and their derivative tumors develop without wnt-1 expression when the majority of C3H primary mammary tumors possess an MMTV-activated wnt-1 gene. C1 BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. NCI,DEPT TUMOR IMMUNOL & BIOL,BETHESDA,MD 20892. FU NCI NIH HHS [CA47112] NR 24 TC 12 Z9 12 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 9 PY 1992 VL 51 IS 5 BP 805 EP 811 DI 10.1002/ijc.2910510523 PG 7 WC Oncology SC Oncology GA JD225 UT WOS:A1992JD22500022 PM 1351886 ER PT J AU BOGUSKI, MS BAIROCH, A ATTWOOD, TK MICHAELS, GS AF BOGUSKI, MS BAIROCH, A ATTWOOD, TK MICHAELS, GS TI PROTO-VAV AND GENE-EXPRESSION SO NATURE LA English DT Letter C1 UNIV GENEVA,DEPT MED BIOCHEM,CH-1211 GENEVA 4,SWITZERLAND. UNIV LEEDS,DEPT BIOCHEM & MOLEC BIOL,LEEDS LS2 9JT,W YORKSHIRE,ENGLAND. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP BOGUSKI, MS (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL,BETHESDA,MD 20892, USA. NR 14 TC 35 Z9 35 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUL 9 PY 1992 VL 358 IS 6382 BP 113 EP 113 DI 10.1038/358113a0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JC583 UT WOS:A1992JC58300034 PM 1614545 ER PT J AU CUTLER, JA BORHANI, NO HENNEKENS, CH WHELTON, P AF CUTLER, JA BORHANI, NO HENNEKENS, CH WHELTON, P TI DISTRESS OVER THE NONEFFECT OF STRESS - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP CUTLER, JA (reprint author), NIH,TOHP COLLABORAT RES GRP,BETHESDA,MD 20892, USA. NR 6 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 JUL 8 PY 1992 VL 268 IS 2 BP 198 EP 199 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA JB279 UT WOS:A1992JB27900019 ER PT J AU YOO, SH AF YOO, SH TI IDENTIFICATION OF THE CA2+-DEPENDENT CALMODULIN-BINDING REGION OF CHROMOGRANIN-A SO BIOCHEMISTRY LA English DT Article ID AMINO-ACID-SEQUENCE; SKELETAL-MUSCLE CALSEQUESTRIN; SECRETORY PROTEINS COMMON; CENTRAL NERVOUS-SYSTEM; LIGHT CHAIN KINASE; SARCOPLASMIC-RETICULUM; MESSENGER-RNA; MOLECULAR-CLONING; CELLS; CHROMAFFIN AB Chromogranin A (CGA), the most abundant protein in bovine adrenal chromaffin granules, is a high-capacity, low-affinity Ca2+-binding protein found in most neuroendocrine cells, and binds calmodulin (CaM) in a Ca2+-dependent manner. The binding of chromogranin A to calmodulin was determined by measuring the intrinsic tryptophan fluorescence of chromogranin A in the presence and absence of Ca2+. Binding was specifically Ca2+-dependent; neither Mg2+ nor Mn2+ could substitute for Ca2+. Chelation of Ca2+ by EGTA completely eliminated the chromogranin A-calmodulin interaction. CaM binding was demonstrated by a synthetic CGA peptide representing residues 40-65. When the CGA peptide and CaM were mixed in the presence of 15 mM CaCl2, the intrinsic tryptophan fluorescence emission underwent a substantial blue-shift, shifting from 350 to 330 nm. Like the intact CGA, the peptide-CaM binding was specifically Ca2+-dependent, and neither Mg2+ nor Mn2+ could induce the binding. Calmodulin bound both to CGA and to the synthetic CGA peptide with a stoichiometry of one to one. The dissociation constants (K(d)) determined by fluorometric titration were 13 nM for the peptide-CaM binding and 17 nM for intact CGA-CaM binding. The K(d) values are comparable to those (approximately 10(-9) M) of other CaM-binding proteins and peptides, demonstrating a tight binding of CaM by CGA. The CaM-binding CGA residues 40-65 are 100% conserved among all the sequenced CGAs in contrast to 50-60% conservation found in the entire sequence, implying essential roles of this region. RP YOO, SH (reprint author), NIDOCD,CELLULAR BIOL LAB,BLDG 36,ROOM 5D-13,BETHESDA,MD 20892, USA. NR 58 TC 25 Z9 25 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 7 PY 1992 VL 31 IS 26 BP 6134 EP 6140 DI 10.1021/bi00141a025 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JC588 UT WOS:A1992JC58800025 PM 1627556 ER PT J AU HARRIS, B MOODY, E SKOLNICK, P AF HARRIS, B MOODY, E SKOLNICK, P TI ISOFLURANE ANESTHESIA IS STEREOSELECTIVE SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Note DE ISOFLURANE; ANESTHESIA; STEREOISOMERS ID HALOTHANE AB The anesthetic effects of the (+) and (-) isomers of isoflurane were determined in mice. Like the clinically important racemate, both isomers produced dose-dependent increases in anesthetic sleep time. A statistically significant (P < 0.005, ANOVA) difference in the potencies of these isomers ((+) > (-)) was observed. To our knowledge, this is the first demonstration of a stereospecific action of a volatile anesthetic in vivo. C1 JOHNS HOPKINS UNIV,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21205. RP HARRIS, B (reprint author), NIDDK,NEUROSCI LAB,BLDG 8,ROOM 111,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 8 TC 68 Z9 68 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JUL 7 PY 1992 VL 217 IS 2-3 BP 215 EP 216 DI 10.1016/0014-2999(92)90875-5 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JE778 UT WOS:A1992JE77800016 PM 1425941 ER PT J AU DECOSTA, B GEORGE, C DOMINGUEZ, C AF DECOSTA, B GEORGE, C DOMINGUEZ, C TI SYNTHESIS OF ISOTHIOCYANATO-1-[1-(2-BENZO[B]THIENYL)CYCLOHEXYL]PIPERIDINES, POTENTIAL IRREVERSIBLE LIGANDS AT THE DOPAMINE REUPTAKE SITE SO JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1 LA English DT Article ID RECEPTORS; COCAINE; COMPLEX; BINDING AB Isomeric isothiocyanate derivatives 2-7 of the potent dopamine re-uptake (DA) inhibitor 1-[1-(2-benzo-[b]thienyl)cyclohexyl]piperidine (BTCP 1) have been synthesized as potential irreversible ligands for this site. NaNO2-CF3CO2H provided a mild procedure for mononitration of the benzo[b]thienyl ring of 1 as a route to aryl isothiocyanates 5-7. Novel methodology, utilizing 3,3-ethylene-dioxypentane-1,5-diol dimethanesulfonate ester is described for the synthesis of piperidone 13, a precursor for 4-isothiocyanatopiperidine 2. NaBH4 or LiAlH4 reduction of 4-(2-benzo[b]thienyl)-4-hydroxycyclohexanone 18 and 4-(2-benzo[b]thienyl)-4-(piperidino)cyclohexanone oxime 35 gives the corresponding cis-diol 21 and cis-cyclohexane-1,4-diamine 36 as the major isomers which have been investigated as precursors to the cyclohexane ring isothiocyanates 3 and 4. Alternative routes to 3 and 4 are compared and their stereochemical outcome investigated. C1 USN,RES LAB,WASHINGTON,DC 20375. RP DECOSTA, B (reprint author), NIDDKD,MED CHEM LAB,BETHESDA,MD 20892, USA. NR 22 TC 5 Z9 5 U1 2 U2 2 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON ROAD, CAMBRIDGE, CAMBS, ENGLAND CB4 4WF SN 0300-922X J9 J CHEM SOC PERK T 1 JI J. Chem. Soc.-Perkin Trans. 1 PD JUL 7 PY 1992 IS 13 BP 1671 EP 1680 PG 10 WC Chemistry, Organic SC Chemistry GA JD469 UT WOS:A1992JD46900024 ER PT J AU HWU, P SCHWARZ, S CUSTER, M SMITH, CA MULE, JJ ROSENBERG, SA AF HWU, P SCHWARZ, S CUSTER, M SMITH, CA MULE, JJ ROSENBERG, SA TI USE OF SOLUBLE RECOMBINANT TNF RECEPTOR TO IMPROVE DETECTION OF TNF SECRETION IN CULTURES OF TUMOR INFILTRATING LYMPHOCYTES SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE TUMOR NECROSIS FACTOR; TUMOR NECROSIS FACTOR RECEPTOR; ELISA, TUMOR NECROSIS FACTOR; TUMOR INFILTRATING LYMPHOCYTE; GENE THERAPY; LYMPHOKINE SECRETION ID NECROSIS FACTOR-ALPHA; PHASE-I; CANCER-PATIENTS; MOLECULAR-CLONING; MURINE TUMORS; GENE-TRANSFER; SERUM FACTOR; IMMUNOTHERAPY; EXPRESSION; MELANOMA AB The accurate quantitation of picogram amounts of TNF is possible by ELISA and is useful in many areas of biomedical research, including studies of TNF release in vitro by stimulated lymphocytes and macrophages, and of serum levels in patients with cancer and sepsis. However, we show in this report that the detection of recombinant TNF standards by ELISA falls over time with incubation at 37-degrees-C, and is further decreased when incubated with tumor infiltrating lymphocytes (TIL), making accurate quantitation difficult. We demonstrate that the soluble dimeric form of the TNF receptor can prevent this decrease, both in the presence and absence of TIL. In contrast, the soluble monomeric TNF receptor was much less effective in preventing this decrease. In addition, the dimeric but not the monomeric TNF receptor was found to inhibit bioactivity of TNF as measured by L929 cytotoxicity. The dimeric TNF receptor does not interfere with the detection of recombinant TNF standards by ELISA, and entirely stabilizes TNF levels incubated over 48 h at 37-degrees-C in the presence and absence of TIL. This protection is specific, and the TNF receptor does not stabilize interferon-gamma. The dimeric form of the soluble TNF receptor has proven useful in detecting TNF released by TIL transduced with the TNF cDNA that are currently being used in studies of the gene therapy of cancer with TIL. The dimeric TNF receptor may also prove useful in the accurate quantitation of TNF released by stimulated lymphocytes and macrophages in vitro, and in the quantitation of serum TNF levels in patients. C1 IMMUNEX CORP,SEATTLE,WA 98101. RP HWU, P (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B46,BETHESDA,MD 20892, USA. NR 28 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JUL 6 PY 1992 VL 151 IS 1-2 BP 139 EP 147 DI 10.1016/0022-1759(92)90112-7 PG 9 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA JD604 UT WOS:A1992JD60400013 PM 1321199 ER PT J AU IRWIN, RP MARAGAKIS, NJ ROGAWSKI, MA PURDY, RH FARB, DH PAUL, SM AF IRWIN, RP MARAGAKIS, NJ ROGAWSKI, MA PURDY, RH FARB, DH PAUL, SM TI PREGNENOLONE SULFATE AUGMENTS NMDA RECEPTOR MEDIATED INCREASES IN INTRACELLULAR CA2+ IN CULTURED RAT HIPPOCAMPAL-NEURONS SO NEUROSCIENCE LETTERS LA English DT Article DE PREGNENOLONE SULFATE; NMDA RECEPTOR; INTRACELLULAR CA2+, NEUROACTIVE STEROID ID GABA-RECEPTOR; ANTAGONIST; DEHYDROEPIANDROSTERONE; STEROIDS; CURRENTS; COMPLEX AB The ability of the neuroactive steroid pregnenolone sulfate to alter N-methyl-D-aspartate (NMDA) receptor-mediated elevations in intracellular Ca2+ ([Ca2+]i) was studied in cultured fetal rat hippocampal neurons using microspectrofluorimetry and the Ca2+ sensitive indicator fura-2. Pregnenolone sulfate (5-250-mu-M) caused a concentration-dependent and reversible potentiation of the rise (up to approximately 800%) in [Ca2+]i induced by NMDA. In contrast, the steroid failed to alter basal (unstimulated) [Ca2+]i or to modify the rise in [Ca2+]i that occurs when hippocampal neurons are depolarized by high K+ in the presence of the NMDA receptor antagonist CPP. These data suggest that the previously reported excitatory properties of pregnenolone sulfate may be due, in part, to an augmentation of the action of glutamic acid at the NMDA receptor. C1 NIMH,CLIN NEUROSCI BRANCH,MOLEC PHARMACOL SECT,BLDG 10,ROOM 4N224,BETHESDA,MD 20892. NINCDS,EPILEPSY RES BRANCH,NEURONAL EXCITABIL SECT,BETHESDA,MD 20892. BOSTON UNIV,SCH MED,DEPT PHARMACOL & EXPTL THERAPEUT,BOSTON,MA 02118. SW FDN BIOMED RES,DEPT ORGAN CHEM,SAN ANTONIO,TX 78228. RI Rogawski, Michael/B-6353-2009; Farb, david/C-7089-2014 OI Rogawski, Michael/0000-0002-3296-8193; Farb, david/0000-0002-9050-6480 NR 21 TC 146 Z9 147 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUL 6 PY 1992 VL 141 IS 1 BP 30 EP 34 DI 10.1016/0304-3940(92)90327-4 PG 5 WC Neurosciences SC Neurosciences & Neurology GA JC930 UT WOS:A1992JC93000008 PM 1387199 ER PT J AU PACE, JR MARTIN, BM PAUL, SM ROGAWSKI, MA AF PACE, JR MARTIN, BM PAUL, SM ROGAWSKI, MA TI HIGH-CONCENTRATIONS OF NEUTRAL AMINO-ACIDS ACTIVATE NMDA RECEPTOR CURRENTS IN RAT HIPPOCAMPAL-NEURONS SO NEUROSCIENCE LETTERS LA English DT Article DE N-METHYL-D-ASPARTATE RECEPTOR; SERINE; CYSTEINE; ALANINE; GLYCINE; PROLINE; HIPPOCAMPAL NEURON ID BRAIN; GLYCINE; RESPONSES; CYSTEINE; AFFINITY; REGIONS; INVITRO; RELEASE; CULTURE AB High concentrations (30-mu-M-5 mM) of the neutral amino acids L-serine, L-cysteine, L-alanine, L-proline and glycine elicited inward current responses when applied to hippocampal neurons patch clamped at -60 mV in the presence of 1-10-mu-M glycine and 1-mu-M strychnine. The amplitude of the response to L-serine increased in a concentration-dependent fashion within the range 0.1-10 mM (EC50, 2.6 mM). L-Serine (1 mM) currents were attenuated by Mg2+ (100-mu-M) and completely blocked by the competitive N-methyl-D-aspartate (NMDA) antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) (30-mu-M). The CPP block could be overcome by raising the concentration of L-serine. We conclude that high concentrations of some neutral amino acids activate NMDA receptor-coupled ion channels by acting as agonists at the NMDA recognition site. C1 NINCDS, EPILEPSY RES BRANCH,NEURONAL EXCITABIL SECT, BLDG 10,ROOM 5C-205, BETHESDA, MD 20892 USA. NIMH, CLIN NEUROSCI BRANCH, MOLEC PHARMACOL SECT, BETHESDA, MD 20892 USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 21 TC 37 Z9 37 U1 0 U2 2 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 JUL 6 PY 1992 VL 141 IS 1 BP 97 EP 100 DI 10.1016/0304-3940(92)90343-6 PG 4 WC Neurosciences SC Neurosciences & Neurology GA JC930 UT WOS:A1992JC93000024 PM 1324446 ER PT J AU MEINKOTH, JL GOLDSMITH, PK SPIEGEL, AM FERAMISCO, JR BURROW, GN AF MEINKOTH, JL GOLDSMITH, PK SPIEGEL, AM FERAMISCO, JR BURROW, GN TI INHIBITION OF THYROTROPIN-INDUCED DNA-SYNTHESIS IN THYROID FOLLICULAR CELLS BY MICROINJECTION OF AN ANTIBODY TO THE STIMULATORY G-PROTEIN OF ADENYLATE-CYCLASE, G(S) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH FACTOR-I; DIBUTYRYL-CYCLIC-AMP; FOS MESSENGER-RNAS; C-FOS; FRTL5 CELLS; THYROGLOBULIN GENE; INCREASE LEVELS; INSULIN; EXPRESSION; CULTURE AB Thyrotropin (TSH) is an important regulator of thyroid follicular cells. While its-role in the maintenance of differentiated functions is undisputed, its role as a mitogen is less clear. TSH induces DNA synthesis and cell proliferation in some cells, while in others, TSH is mitogenic only in the presence of additional growth factors such as insulin-like growth factor-1. TSH causes elevations in intracellular cAMP and is thought to utilize this second messenger system in its mitogenic action. We studied TSH as a mitogen in Wistar rat thyroid cells (WRT) (Brandi, M. L., Rotella, C. M., Mavilia, C., Franceschelli, F., Tanini, A., and Toccafondi, R. (1987) Mol. Cell. Endocrinol. 54, 91-103) and examined the role of the guanine nucleotide binding protein, G(s), in its mitogenic action. WRT cells synthesized DNA in response to TSH and elevations in cAMP. In addition, TSH caused a rapid stimulation of an indicator gene whose expression is regulated by cAMP response elements. Following microinjection of an inhibitory polyclonal antibody raised against the G(s) protein, both TSH-induced changes in gene expression and DNA synthesis were significantly reduced. These results demonstrate that virtually all of the mitogenic action of TSH is transduced through the G(s) protein in WRT cells, presumably through the regulation of adenylate cyclase. Whether all or only part of TSH action is mediated by cAMP and the cAMP-dependent protein kinase remains to be determined. C1 UNIV CALIF SAN DIEGO,CTR CANC,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,DEPT PHARMACOL,LA JOLLA,CA 92093. NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BETHESDA,MD 20892. RP MEINKOTH, JL (reprint author), UNIV CALIF SAN DIEGO,DEPT MED 0613K,LA JOLLA,CA 92093, USA. NR 47 TC 38 Z9 38 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 JUL 5 PY 1992 VL 267 IS 19 BP 13239 EP 13245 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JB746 UT WOS:A1992JB74600025 PM 1377681 ER PT J AU KAISER, SM LANEUVILLE, P BERNIER, SM RHIM, JS KREMER, R GOLTZMAN, D AF KAISER, SM LANEUVILLE, P BERNIER, SM RHIM, JS KREMER, R GOLTZMAN, D TI ENHANCED GROWTH OF A HUMAN KERATINOCYTE CELL-LINE INDUCED BY ANTISENSE RNA FOR PARATHYROID HORMONE-RELATED PEPTIDE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SYNTHETIC PEPTIDE; ADENYLATE-CYCLASE; BONE-RESORPTION; GENE-EXPRESSION; PROTEIN; MALIGNANCY; INVITRO; INVIVO; DIFFERENTIATION; HYPERCALCEMIA AB We have used antisense RNA technology to inhibit endogenous parathyroid hormone-related peptide (PTHRP) production in the established human keratinocyte cell line, HPK1A, in order to assess the role of PTHRP as a potential modulator of cell growth. Rat PTHRP cDNA was cloned into the replication defective retroviral vector pYN in an antisense orientation and a stable cell line (HPK1A-AS) was generated after infection by amphotropic virus and selection by the neomycin derivative, G418. Expression of the transfected antisense sequence was confirmed with an RNA sense probe for PTHRP. The effect of the retrovirally mediated gene transfer on the endogenous PTHRP transcript was examined with an RNA antisense probe which demonstrated an absence of the endogenous transcript in HPK1A-AS cells. A 1.6-kilobase transcript was, however, present in equivalent quantities in both uninfected HPK1A and pYN-infected (HPK1A-pYN) cells. Immunocytochemistry and assessment of PTHRP secretion into the medium using an NH2-terminal radioimmunoassay and a UMR 106 adenylate cyclase bioassay confirmed the absence of PTHRP in HPK1A-AS cells. Examination of the inhibition of PTHRP production on cell growth demonstrated a reduction in doubling time and an increase in [H-3]thymidine incorporation. Cell cycle analysis showed an increase in the proportion of the cell population in the S phase (relative to G0/G1) in HPK1A-AS cells compared to HPK1A or HPK1A-pYN cells. These data, therefore, indicate that endogenous PTHRP acts as an effective inhibitor of cell growth in this keratinocyte model and that this action occurs, at least in part, by diminishing entry into the S phase of the cell cycle. Furthermore, the antisense RNA method is a potent one to evaluate the cellular actions of PTHRP. C1 ROYAL VICTORIA HOSP,CALCIUM RES LAB,RM H467,687 PINE AVE W,MONTREAL H3A 1A1,QUEBEC,CANADA. MCGILL UNIV,DEPT MED,MONTREAL H3A 1A1,QUEBEC,CANADA. MCGILL UNIV,DEPT ONCOL,MONTREAL H3A 1A1,QUEBEC,CANADA. MCGILL UNIV,DEPT PHYSIOL,MONTREAL H3A 1A1,QUEBEC,CANADA. NCI,BETHESDA,MD 20892. NR 51 TC 130 Z9 130 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 JUL 5 PY 1992 VL 267 IS 19 BP 13623 EP 13628 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JB746 UT WOS:A1992JB74600083 PM 1618864 ER PT J AU LOHSE, P RADER, DJ BREWER, HB AF LOHSE, P RADER, DJ BREWER, HB TI HETEROZYGOSITY FOR APOLIPOPROTEIN-E-4(PHILADELPHIA)(GLU(13)-]LYS, ARG(145)-]CYS) IS ASSOCIATED WITH INCOMPLETE DOMINANCE OF TYPE-III HYPERLIPOPROTEINEMIA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN APOLIPOPROTEIN-E; RECEPTOR-BINDING ACTIVITY; AMINO-ACID-SEQUENCE; HUMAN-E APOPROTEIN; FAMILIAL DYSBETALIPOPROTEINEMIA; VARIANT; HETEROGENEITY; PATIENT; GENE; E2(LYS146->GLN) AB Apolipoprotein (apo) E-4Philadelphia is a double mutant of apoE in which residue 13 of the mature protein, glutamic acid (GAG), is replaced by lysine (AAG) and amino acid 145, arginine (CGT), is converted to cysteine (TGT). These mutations result in two restriction fragment length polymorphisms for the enzymes AvaI and BbvI, a smaller apparent molecular weight of apoE-4Philadelphia on sodium dodecyl polyacrylamide gels, and severe type III hyperlipoproteinemia (HLP) in a 24-year-old homozygous female (Lohse, P., Mann, W. A., Stein, E. A., and Brewer, H. B., Jr. (1991) J. Biol. Chem. 266, 10479-10484). In the current study, we have extended our analysis to include nine additional family members of the Philadelphia kindred spanning four generations. DNA and protein analysis demonstrated that the originally described propositus is a true homozygote for the epsilon-4Philadelphia allele and that six of the nine family members are heterozygous for the mutated allele and the normal-epsilon-3 allele or, in one case, the epsilon-4 allele. Heterozygosity for apoE-4Philadelphia leads to the expression of a moderate form of type III HLP without clinical manifestations. These results are consistent with a dominant mode of inheritance of this dyslipoproteinemia. The simultaneous presence of unaffected individuals, heterozygotes, and a homozygote in the Philadelphia kindred makes it possible for the first time to demonstrate that the mutant apoE exhibits an incomplete or partial dominance of type III HLP. Heterozygosity for the normal epsilon-3 allele appears to have an influence on the expression of type III HLP, resulting in a phenotype intermediate between that of the two homozygous states. RP LOHSE, P (reprint author), NHLBI,MOLEC DIS BRANCH,9000 ROCKVILLE PIKE,BLDG 10,RM 7N117,BETHESDA,MD 20892, USA. NR 39 TC 25 Z9 25 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 JUL 5 PY 1992 VL 267 IS 19 BP 13642 EP 13646 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JB746 UT WOS:A1992JB74600086 PM 1352296 ER PT J AU FRANK, SJ CENCIARELLI, C NIKLINSKA, BB LETOURNEUR, F ASHWELL, JD WEISSMAN, AM AF FRANK, SJ CENCIARELLI, C NIKLINSKA, BB LETOURNEUR, F ASHWELL, JD WEISSMAN, AM TI MUTAGENESIS OF T-CELL ANTIGEN RECEPTOR-ZETA CHAIN TYROSINE RESIDUES EFFECTS ON TYROSINE PHOSPHORYLATION AND LYMPHOKINE PRODUCTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHOROTHIOATE-MODIFIED DNA; SIGNAL TRANSDUCTION; MOLECULAR-CLONING; ETA-CHAIN; ACTIVATION; PROTEIN; IDENTIFICATION; COMPLEX; POLYPEPTIDE; ANTIBODIES AB Occupancy of the T cell antigen receptor triggers a complex set of events that culminate in cellular activation. It is clear that tyrosine kinases play important roles in this process. The zeta-subunit of the T cell antigen receptor is a 16-kDa transmembrane structure that exists primarily as a disulfide-linked homodimer. On receptor activation, a subset of zeta-molecules undergo tyrosine phosphorylation. To evaluate this process and the role of zeta-phosphorylation in T cell activation, site-specific mutagenesis of the intracytoplasmic tyrosines of zeta has been carried out. Analysis of cells expressing these mutant zeta-subunits demonstrated that multiple tyrosines underwent phosphorylation in response to receptor engagement, and that the four most carboxyl tyrosines were most crucial to this process. Despite abnormalities in phosphorylation induced by the mutations, lymphokine production in these transfectants was unaffected. Hence, although zeta is a prominent substrate for a receptor-activated tyrosine kinase, neither the mutation of individual tyrosines nor the alteration of the phosphorylation state of the molecule substantively affected the coupling of T cell receptor activation to lymphokine production. These findings raise questions regarding the role of zeta-phosphorylation in T cell activation. C1 NCI,EXPTL IMMUNOL BRANCH,BLDG 10,RM 4B17,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. NCI,BIOL RESPONSE MODIFIERS PROGRAM,IMMUNE CELL BIOL SECT,BETHESDA,MD 20892. NR 41 TC 34 Z9 34 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 JUL 5 PY 1992 VL 267 IS 19 BP 13656 EP 13660 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JB746 UT WOS:A1992JB74600088 PM 1535630 ER PT J AU KIM, SJ PARK, K KOELLER, D KIM, KY WAKEFIELD, LM SPORN, MB ROBERTS, AB AF KIM, SJ PARK, K KOELLER, D KIM, KY WAKEFIELD, LM SPORN, MB ROBERTS, AB TI POSTTRANSCRIPTIONAL REGULATION OF THE HUMAN TRANSFORMING GROWTH FACTOR-BETA-1 GENE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACCOMPANIES VIRAL TRANSFORMATION; IRON-RESPONSIVE ELEMENT; FERRITIN MESSENGER-RNA; FACTOR-BETA; TRANSLATIONAL REGULATION; MOUSE EPIDERMIS; AP-1 COMPLEX; CELL-LINE; EXPRESSION; PROMOTER AB Since many lines of evidence suggest that expression of the transforming growth factor-beta-1 (TGF-beta-1) gene may be regulated post-transcriptionally, we examined the effect of the 5'-untranslated region (UTR) of this gene on TGF-beta-1 expression. For this purpose, fragments of the 840-nucleotide highly GC-rich TGF-beta-1 5'-UTR were inserted into the 5'-UTR of the structural gene for human growth hormone driven by the simian virus 40 early promoter. A portion of the 5'-UTR of TGF-beta-1 mRNA spanning the sequences from +11 to +147 was shown to inhibit growth hormone expression by as much as 22-fold. This effect was cell-specific; growth hormone production was inhibited in PC-3 human prostate adenocarcinoma and A-549 human lung adenocarcinoma cells, while no effect was seen in rat pheochromocytoma PC12 cells, which show efficient translation of endogenous TGF-beta-1 mRNA. Computer analysis showed that this region of the 5'-UTR contained a stable secondary stem-loop structure spanning sequences +49 to +76. This stem-loop region alone is sufficient to inhibit expression of the growth hormone gene, suggesting that it plays an important role in post-transcriptional regulation of TGF-beta-1 gene expression. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. RP KIM, SJ (reprint author), NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892, USA. NR 38 TC 172 Z9 174 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 5 PY 1992 VL 267 IS 19 BP 13702 EP 13707 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JB746 UT WOS:A1992JB74600095 PM 1618868 ER PT J AU WEICKERT, MJ ADHYA, S AF WEICKERT, MJ ADHYA, S TI ISOREPRESSOR OF THE GAL REGULON IN ESCHERICHIA-COLI SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE MGL OPERON; GAL OPERON; GENE REGULATION; CROSSTALK; GALS ID TRANSPORT-SYSTEM; REPRESSOR; SEQUENCE; OPERON; GENE; EXPRESSION; COMPLEXES; FUSIONS; PROTEIN; DNA C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 51 TC 39 Z9 41 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUL 5 PY 1992 VL 226 IS 1 BP 69 EP 83 DI 10.1016/0022-2836(92)90125-4 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JC809 UT WOS:A1992JC80900009 PM 1619663 ER PT J AU CHANDRASEKHAR, I CLORE, GM SZABO, A GRONENBORN, AM BROOKS, BR AF CHANDRASEKHAR, I CLORE, GM SZABO, A GRONENBORN, AM BROOKS, BR TI A 500-PS MOLECULAR-DYNAMICS SIMULATION STUDY OF INTERLEUKIN-1-BETA IN WATER - CORRELATION WITH NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY AND CRYSTALLOGRAPHY SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE INTERLEUKIN-1-BETA; MOLECULAR DYNAMICS SIMULATION; NMR RELAXATION; X-RAY B-FACTORS ID MODEL-FREE APPROACH; N-15-H-1 NMR-SPECTROSCOPY; ATOMIC FLUCTUATIONS; PROTEIN DYNAMICS; RELAXATION; LYSOZYME; MACROMOLECULES; DIFFRACTION; RESOLUTION; REFINEMENT C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. RP CHANDRASEKHAR, I (reprint author), NIDDKD,DIV COMP RES & TECHNOL,MOLEC GRAPH & SIMULAT LAB,BLDG 12A,BETHESDA,MD 20892, USA. RI Clore, G. Marius/A-3511-2008; Szabo, Attila/H-3867-2012 OI Clore, G. Marius/0000-0003-3809-1027; NR 42 TC 158 Z9 158 U1 0 U2 14 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 JUL 5 PY 1992 VL 226 IS 1 BP 239 EP 250 DI 10.1016/0022-2836(92)90136-8 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JC809 UT WOS:A1992JC80900020 PM 1619653 ER PT J AU HALL, P BOICE, JD BERG, G BJELKENGREN, G ERICSSON, UB HALLQUIST, A LIDBERG, M LUNDELL, G MATTSSON, A TENNVALL, J WIKLUND, K HOLM, LE AF HALL, P BOICE, JD BERG, G BJELKENGREN, G ERICSSON, UB HALLQUIST, A LIDBERG, M LUNDELL, G MATTSSON, A TENNVALL, J WIKLUND, K HOLM, LE TI LEUKEMIA INCIDENCE AFTER I-131 EXPOSURE SO LANCET LA English DT Article ID CANCER; MORTALITY; LEUKEMIA; RADIOTHERAPY; I-131; RISK AB Leukaemia is one of the most prominent late effects of exposure to ionising radiation. We have studied the incidence of leukaemia among 46 988 Swedish patients exposed to iodine-131 (I-131) for diagnostic reasons or to treat hyperthyroidism or thyroid cancer. The observed number of leukaemias was compared with that expected based on incidence data from the general population. The mean absorbed dose to the bone marrow was estimated as 14 mGy (range 0.01-2.226). 195 leukaemias occurred more than 2 years after exposure, and the standardised incidence ratio (SIR) was 1.09 (95% confidence interval 0.94-1.25). Similar, but again not significantly, increased risks were seen for chronic lymphocytic leukaemia (CLL) (SIR=1.08), a malignant condition not found to be increased after irradiation, and for non-CLL (SIR=1.09). The risk of leukaemia did not vary by sex, age, time, or radiation dose from I-131. One reason for the absence of a radiation effect, other than chance, includes the possible lowering of risk when exposure is protracted over time as occurs with I-131. Excess leukaemia risks of more than 25% could thus be excluded with high assurance in this population of mainly adults. These results should be reassuring to patients exposed to I-131 in medical practice and to most individuals exposed to the fall-out from the Chernobyl accident. C1 KAROLINSKA HOSP,RADIUM HEMMET,CTR ONCOL,S-10401 STOCKHOLM,SWEDEN. KAROLINSKA HOSP,RADIUM HEMMET,DEPT CANC EPIDEMIOL,S-10401 STOCKHOLM,SWEDEN. KAROLINSKA HOSP,RADIUM HEMMET,DEPT CANC PREVENT,S-10401 STOCKHOLM,SWEDEN. SODER SJUKHUSET,DEPT HOSP PHYS,STOCKHOLM,SWEDEN. NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. SAHLGRENS UNIV HOSP,DEPT GEN ONCOL,S-41345 GOTHENBURG,SWEDEN. MALMO GEN HOSP,DEPT GEN ONCOL,S-21401 MALMO,SWEDEN. MALMO GEN HOSP,DEPT INTERNAL MED,S-21401 MALMO,SWEDEN. UMEA UNIV HOSP,DEPT GEN ONCOL,S-90185 UMEA,SWEDEN. UNIV LUND HOSP,DEPT GEN ONCOL,S-22185 LUND,SWEDEN. RP HALL, P (reprint author), KAROLINSKA HOSP,RADIUM HEMMET,DEPT GEN ONCOL,S-10401 STOCKHOLM,SWEDEN. RI Tennvall, Jan/F-8760-2014; Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NCI NIH HHS [N01-CP-51034] NR 25 TC 90 Z9 92 U1 0 U2 2 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUL 4 PY 1992 VL 340 IS 8810 BP 1 EP 4 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA JC354 UT WOS:A1992JC35400001 PM 1351599 ER PT J AU LAIRD, JMA BENNETT, GJ AF LAIRD, JMA BENNETT, GJ TI DORSAL-ROOT POTENTIALS AND AFFERENT INPUT TO THE SPINAL-CORD IN RATS WITH AN EXPERIMENTAL PERIPHERAL NEUROPATHY SO BRAIN RESEARCH LA English DT Article DE NERVE INJURY; PRESYNAPTIC INHIBITION; DORSAL ROOT POTENTIAL; COMPOUND ACTION POTENTIAL; SPINAL CORD; PERIPHERAL NERVE ID SCIATIC-NERVE; TRANSSYNAPTIC DEGENERATION; MONONEUROPATHY; INJURY; CONSTRICTION; STRYCHNINE; CAPSAICIN; NEURONS; HORN AB Compound action potentials (CAPs), dorsal root potentials (DRPs) and cord dorsum potentials evoked by stimulating the sciatic nerves have been measured in 4 control rats and in 19 rats with a constriction injury of one sciatic nerve produced by loose ligation of the nerve at mid-thigh level 5 days (n = 8) or 10 days (n = 11) before the acute experiments. The contralateral nerve was exposed but not ligated in a sham procedure. In all cases, the nerve was stimulated proximal to the lesion. At 5 days post-operative (PO) the maximal A-fibre CAPs on the nerve-injured side were not significantly different from those on the sham-operated side. At 10 days PO all animals showed a decrease in the CAP on the nerve-injured side. The mean CAP area on the nerve-injured side was 74.0% +/- 4.2 of the sham-operated side, which was significantly different (P < 0.005). The sciatic nerves and L5 dorsal roots from 4 of the 10 day PO animals were examined histologically and showed no signs of demyelination or degeneration. The amplitude and area of the maximal DRPs were significantly smaller on the nerve-injured side than on the sham-operated side in all of the nerve-injured animals (P < 0.01 at 5 days PO; P < 0.05 at 10 days PO). The mean area of DRPs from the nerve-injured side was 61.7% +/- 10.1 and 46.8% +/- 7.5 of the DRPs from the sham-operated side in the 5 and 10 day PO animals, respectively. The DRPs evoked by sub-maximal afferent volleys were also measured. In all of the nerve-injured animals the CAP-DRP curve on the nerve-injured side was shifted to the right compared to that of the sham-operated side, such that a given size of CAP evoked a smaller DRP on the nerve-injured side than on the sham-operated side. We conclude that the constriction injury produces a decrease in the DRP generated by a volley in the injured nerve and that this change is independent of the decrease in the CAP seen in the injured nerve. We propose that the constriction injury affects the central mechanism responsible for generating primary afferent depolarization (PAD), and thus the pre-synaptic inhibitory control of the afferent input from the injured nerve is impaired. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. NR 29 TC 75 Z9 75 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 3 PY 1992 VL 584 IS 1-2 BP 181 EP 190 DI 10.1016/0006-8993(92)90893-E PG 10 WC Neurosciences SC Neurosciences & Neurology GA JG689 UT WOS:A1992JG68900023 PM 1515937 ER PT J AU ECKARDT, MJ CAMPBELL, GA MARIETTA, CA MAJCHROWICZ, E RAWLINGS, RR WEIGHT, FF AF ECKARDT, MJ CAMPBELL, GA MARIETTA, CA MAJCHROWICZ, E RAWLINGS, RR WEIGHT, FF TI ETHANOL DEPENDENCE AND WITHDRAWAL SELECTIVELY ALTER LOCALIZED CEREBRAL GLUCOSE-UTILIZATION SO BRAIN RESEARCH LA English DT Article DE ETHANOL DEPENDENCY; ETHANOL WITHDRAWAL; 2-DEOXYGLUCOSE ID RAT-BRAIN; BLOOD-FLOW; FUNCTIONAL-ACTIVITY; CONSUMPTION; AMPHETAMINE; METABOLISM; DIAZEPAM; SYSTEM AB The 2-deoxyglucose technique was used to determine local cerebral glucose utilization (LCGU) in over 50 brain regions of rats physically dependent upon ethanol and compared to those of acutely intoxicated and those undergoing an overt ethanol-withdrawal syndrome. Dependent-intoxicated rats (average blood ethanol concentration 64 mM) had decreased LCGU in 13/54 regions, including those associated with the limbic system, cerebellum, and motor system. The ethanol withdrawal syndrome was associated with 17/50 gray regions showing an increase, including regions involved with motor function, auditory system, and mammillary bodies-anterior thalamus-cingulate cortex pathway. The most pronounced differences between these groups occurred in regions associated with motor function, cerebellar function, anterior thalamus, and median raphe. Comparisons between dependent-intoxicated and acutely intoxicated rats (average blood ethanol concentration 66 MM) revealed that acute intoxication was associated with a relatively greater reduction in LCGU in regions involved with sensory-related functions, mammillary bodies, and median raphe. With the development of dependence, adaptation occurred in these regions except for inferior colliculus and median raphe. Dependence was also associated with a relative decrease in LCGU in white matter, limbic system, and extrapyramidal motor system. C1 NIAAA,DICBR,PHYSIOL & PHARMACOL STUDIES LAB,BETHESDA,MD 20892. RP ECKARDT, MJ (reprint author), NIAAA,CLIN STUDIES LAB,BLDG 10,ROOM 3B-19,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Campbell, Gerald/0000-0002-7123-6884 NR 31 TC 13 Z9 13 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 JUL 3 PY 1992 VL 584 IS 1-2 BP 244 EP 250 DI 10.1016/0006-8993(92)90901-K PG 7 WC Neurosciences SC Neurosciences & Neurology GA JG689 UT WOS:A1992JG68900031 PM 1515942 ER PT J AU LEW, R PATEL, A VAUGHAN, RA WILSON, A KUHAR, MJ AF LEW, R PATEL, A VAUGHAN, RA WILSON, A KUHAR, MJ TI MICROHETEROGENEITY OF DOPAMINE TRANSPORTERS IN RAT STRIATUM AND NUCLEUS-ACCUMBENS SO BRAIN RESEARCH LA English DT Article DE DOPAMINE TRANSPORTER; STRIATUM; NUCLEUS ACCUMBENS; [I-125]DEEP; TRANSPORTER HETEROGENEITY ID N-ACETYLGLUCOSAMINIDASE-F; COCAINE RECEPTORS; HIGH-MANNOSE; SIALIC-ACID; BRAIN; BINDING; CHAINS; DEGLYCOSYLATION; GLYCOPROTEINS; EXPRESSION AB Previously we have shown that the [I-125]DEEP-labeled dopamine transporter from the rat nucleus accumbens has a higher apparent molecular weight than that from striatum. The present study confirms and extends these observations24. Experiments with nucleus accumbens showed [I-125]-DEEP to specifically bind to a protein with an apparent molecular weight of 76 kDa and with the pharmacological properties of the dopamine transporter. In exoglycosidase studies, treatment with neuraminidase, but not alpha-mannosidase, reduced the apparent molecular weight of the dopamine transporter from both the striatum and nucleus accumbens; however, a difference in the apparent molecular weight was still observed. N-Glycanase treatment, on the other hand, did reduce the apparent molecular weight of the dopamine transporters from the two regions to a similar value, approximately 56 kDa. In radioligand binding studies examining the effect of partial deglycosylation on striatal dopamine transporters, neuraminidase did not affect specific [H-3]WIN 35,428 binding at 4 and 40 nM concentrations. In conclusion, the present study demonstrates that the difference in the apparent molecular weight of the dopamine transporter from these two regions is due to a difference in glycosylation and that the dopamine transporter from both regions contains similar amounts of sialic acid in their carbohydrate structure. Furthermore, the present data also indicate that the polypeptide portion of the dopamine transporter from both regions could be the same gene product. C1 NIDA,ADDICT RES CTR,NEUROSCI BRANCH,POB 5180,BALTIMORE,MD 21224. RI Wilson, Alan/A-1788-2011 NR 38 TC 54 Z9 54 U1 1 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 JUL 3 PY 1992 VL 584 IS 1-2 BP 266 EP 271 DI 10.1016/0006-8993(92)90905-O PG 6 WC Neurosciences SC Neurosciences & Neurology GA JG689 UT WOS:A1992JG68900035 PM 1515945 ER PT J AU GOURAS, GK RANCE, NE YOUNG, WS KOLIATSOS, VE AF GOURAS, GK RANCE, NE YOUNG, WS KOLIATSOS, VE TI TYROSINE-HYDROXYLASE-CONTAINING NEURONS IN THE PRIMATE BASAL FOREBRAIN MAGNOCELLULAR COMPLEX SO BRAIN RESEARCH LA English DT Note DE CATECHOLAMINERGIC; DIAGONAL BAND; HUMAN; MONKEY; NUCLEUS BASALIS; SEPTUM ID IMMUNOREACTIVE NEURONS; CHOLINE-ACETYLTRANSFERASE; CEREBRAL-CORTEX; RHESUS-MONKEY; SEPTAL AREA; RAT-BRAIN; SUBSTANTIA INNOMINATA; ACID DECARBOXYLASE; ALZHEIMERS-DISEASE; DIAGONAL BAND AB Immunocytochemistry and in situ hybridization for tyrosine hydroxylase (TH) were used to study the distribution of putative catecholaminergic neurons in the basal forebrain magnocellular complex (BFMC) of monkeys and humans. Magnocellular TH-expressing neurons in the primate BFMC are distributed along a rostrocaudal gradient, with the largest proportion of these cells located in the medial septal nucleus and nucleus of the diagonal band of Broca; smaller TH-containing neurons generally follow the same distribution. These findings suggest that, within rostromedial segments of the BFMC, there is a distinct subpopulation of neurons that express catecholamine-synthesizing enzymes. Further research is necessary to establish whether these neurons utilize one or more catecholamines as neurotransmitters. C1 JOHNS HOPKINS UNIV,SCH MED,NEUROPATHOL LAB,558 ROSS RES BLDG,720 RUTLAND AVE,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. UNIV ARIZONA,COLL MED,DEPT PATHOL,TUCSON,AZ 85721. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RI Young, W Scott/A-9333-2009; Gouras, Gunnar/B-3021-2010 OI Young, W Scott/0000-0001-6614-5112; Gouras, Gunnar/0000-0002-5500-6325 FU NIA NIH HHS [AG 05146]; NINDS NIH HHS [NS 20471, NS 07179] NR 44 TC 16 Z9 16 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 JUL 3 PY 1992 VL 584 IS 1-2 BP 287 EP 293 DI 10.1016/0006-8993(92)90907-Q PG 7 WC Neurosciences SC Neurosciences & Neurology GA JG689 UT WOS:A1992JG68900037 PM 1355392 ER PT J AU HIGHET, RJ JONES, TH AF HIGHET, RJ JONES, TH TI THE TAUTOMERISM OF A PHOSPHONO ENAMINE SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Note RP HIGHET, RJ (reprint author), NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892, USA. NR 15 TC 3 Z9 3 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 JUL 3 PY 1992 VL 57 IS 14 BP 4038 EP 4040 DI 10.1021/jo00040a062 PG 3 WC Chemistry, Organic SC Chemistry GA JC511 UT WOS:A1992JC51100062 ER PT J AU MILLER, LH AF MILLER, LH TI THE CHALLENGE OF MALARIA SO SCIENCE LA English DT Editorial Material RP MILLER, LH (reprint author), NIAID,MALARIA RES LAB,BETHESDA,MD 20892, USA. NR 12 TC 37 Z9 38 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 JUL 3 PY 1992 VL 257 IS 5066 BP 36 EP 37 DI 10.1126/science.1621092 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JC165 UT WOS:A1992JC16500022 PM 1621092 ER PT J AU NAKAYAMA, T UEDA, Y YAMADA, H SHORES, EW SINGER, A JUNE, CH AF NAKAYAMA, T UEDA, Y YAMADA, H SHORES, EW SINGER, A JUNE, CH TI INVIVO CALCIUM ELEVATIONS IN THYMOCYTES WITH T-CELL RECEPTORS THAT ARE SPECIFIC FOR SELF LIGANDS SO SCIENCE LA English DT Article ID TRANSGENIC MICE; CD4+8+ THYMOCYTES; ANTIGEN RECEPTOR; TOLERANCE; EXPRESSION; REACTIVITY; SELECTION; PRODUCTS; DELETION; IMMATURE AB Selection of the T cell receptor (TCR) repertoire in the thymus probably involves TCR-mediated signals transduced in developing thymocytes after interaction with thymic stromal cells bearing self ligands. TCR-transduced signals should have identifiable consequences that would distinguish thymocytes whose TCRs have been engaged by self ligands from those whose TCRs have not. Among thymocytes expressing a transgenic TCR of defined specificity, a large number had elevated intracellular calcium concentrations but only when resident in a negatively selecting thymus in which their self ligand was expressed. Thus, developing thymocytes are stimulated by endogenous ligands in vivo to mobilize intracellular calcium, and increased intracellular calcium concentrations may reflect the consequences of intrathymic signaling associated with thymic negative selection. C1 NCI,EXPTL IMMUNOL BRANCH,BLDG 10 ROOM 4B-17,BETHESDA,MD 20892. USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20814. RI Nakayama, Toshinori/E-1067-2017 NR 20 TC 65 Z9 66 U1 1 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 3 PY 1992 VL 257 IS 5066 BP 96 EP 99 DI 10.1126/science.1621102 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JC165 UT WOS:A1992JC16500039 PM 1621102 ER PT J AU SORRENTINO, BP BRANDT, SJ BODINE, D GOTTESMAN, M PASTAN, I CLINE, A NIENHUIS, AW AF SORRENTINO, BP BRANDT, SJ BODINE, D GOTTESMAN, M PASTAN, I CLINE, A NIENHUIS, AW TI SELECTION OF DRUG-RESISTANT BONE-MARROW CELLS INVIVO AFTER RETROVIRAL TRANSFER OF HUMAN MDR1 SO SCIENCE LA English DT Article ID HEMATOPOIETIC STEM-CELLS; GENE-TRANSFER; MULTIDRUG RESISTANCE; EXPRESSION; RECIPIENTS; LINE AB Experiments were performed to determine if retroviral-mediated transfer of the human multidrug resistance 1 gene (MDR1) into murine bone marrow cells would confer drug resistance to the cells and whether the MDR1 gene could be used as a dominant selectable marker in vivo. When mice transplanted with bone marrow cells containing a transferred MDR1 gene were treated with the cytotoxic drug taxol, a substantial enrichment for transduced bone marrow cells was observed. This demonstration of positive selection establishes the ability to amplify clones of transduced hematopoietic cells in vivo and suggests possible applications in human therapy. C1 VANDERBILT UNIV,DEPT MED,NASHVILLE,TN 37232. VANDERBILT UNIV,DEPT CELL BIOL,NASHVILLE,TN 37232. NCI,DIV CANC BIOL & DIAG,CELL BIOL LAB,BETHESDA,MD 20892. NCI,DIV CANC BIOL & DIAG,MOLEC BIOL LAB,BETHESDA,MD 20892. RP SORRENTINO, BP (reprint author), NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892, USA. NR 17 TC 472 Z9 477 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 3 PY 1992 VL 257 IS 5066 BP 99 EP 103 DI 10.1126/science.1352414 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JC165 UT WOS:A1992JC16500040 PM 1352414 ER PT J AU KARLHOFER, FM RIBAUDO, RK YOKOYAMA, WM AF KARLHOFER, FM RIBAUDO, RK YOKOYAMA, WM TI MHC CLASS-I ALLOANTIGEN SPECIFICITY OF LY-49+ IL-2-ACTIVATED NATURAL-KILLER-CELLS SO NATURE LA English DT Article ID MONOCLONAL-ANTIBODIES; EXPRESSION; ANTIGEN; IDENTIFICATION; RECEPTOR; GENE; MOLECULES; SUSCEPTIBILITY; RECOGNITION; RESISTANCE AB THE molecular basis of target cell recognition by CD3- natural killer (NK) cells is poorly understood, despite the ability of NK cells to lyse specific tumour cells 1,2. In general, target cell major histocompatibility complex (MHC) class I antigen expression correlates with resistance to NK cell-mediated lysis 3-9, possibly because NK cell-surface molecules engage MHC class I antigens and consequently deliver inhibitory signals 3,4. Natural killer cell allospecificity involves the MHC class I peptide-binding cleft 10, and further understanding of this allospecificity should provide insight into the molecular mechanisms of NK cell recognition. The Ly-49 cell surface molecule is expressed by 20% of CD3- NK cells 11 in C57BL/6 mice (H-2b). Here we show that C57BL/6-derived, interleukin-2-activated NK cells expressing Ly-49 do not lyse target cells displaying H-2d or H-2k despite efficient spontaneous lysis by Ly-49- effector cells. This preferential resistance correlates with expression of target cell MHC class I antigens. Transfection and expression of H-2D(d), but not H-2K(d) or H-2L(d), renders a susceptible target (H-2b) resistant to Ly-49+ effector cells. The transfected resistance is abrogated by monoclonal antibodies directed against Ly-49 or the alpha-1/alpha-2 domains of H-2D(d), suggesting that Ly-49 specifically interacts with the peptide-binding domains of the MHC class I alloantigen, H-2D(d) Inas-much as Ly49+ effector cells cannot be stimulated to lyse H-2D(d) targets, our results indicate that NK cells may possess inhibitory receptors that specifically recognize MHC class I antigens. C1 SAN FRANCISCO GEN HOSP,MED SERV,SAN FRANCISCO,CA 94110. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RP KARLHOFER, FM (reprint author), UNIV CALIF SAN FRANCISCO,DEPT MED,ROSALIND RUSSELL ARTHRITIS RES LAB,SAN FRANCISCO,CA 94143, USA. NR 34 TC 679 Z9 685 U1 1 U2 14 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUL 2 PY 1992 VL 358 IS 6381 BP 66 EP 70 DI 10.1038/358066a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JB341 UT WOS:A1992JB34100055 PM 1614533 ER PT J AU PARASCANDOLA, J AF PARASCANDOLA, J TI PARTNERS IN SCIENCE - FOUNDATIONS AND NATURAL SCIENTISTS, 1900-1945 - KOHLER,RE SO ACADEME-BULLETIN OF THE AAUP LA English DT Book Review RP PARASCANDOLA, J (reprint author), NATL LIB MED,DIV HIST MED,BETHESDA,MD 20209, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSN UNIV PROFESSORS PI WASHINGTON PA SUITE 500 1012 14TH ST, NW, WASHINGTON, DC 20005 SN 0190-2946 J9 ACADEME JI Academe-Bull. AAUP PD JUL-AUG PY 1992 VL 78 IS 4 BP 47 EP 48 PG 2 WC Education & Educational Research SC Education & Educational Research GA JH858 UT WOS:A1992JH85800019 ER PT J AU SHMUELI, U WEISS, GH AF SHMUELI, U WEISS, GH TI EXACT CONDITIONAL JOINT PROBABILITY-DISTRIBUTION OF A 3-PHASE INVARIANT IN SPACE GROUP P2 .1. DERIVATION OF THE FOURIER COEFFICIENTS SO ACTA CRYSTALLOGRAPHICA SECTION A LA English DT Article AB We extend our study of the conditional probability density function (c.p.d.f.) of the three-phase invariant for the space group PI [Shmueli, Rabinovich & Weiss (1989). Acta Cryst. A45, 361-367] to the monoclinic space group P2. A detailed derivation of the characteristic function (and hence Fourier coefficients) of the latter c.p.d.f. is presented in this paper, as well as some simplifications of the resulting expressions. C1 NIH,DIV COMP SCI & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892. RP SHMUELI, U (reprint author), TEL AVIV UNIV,SCH CHEM,IL-69978 TEL AVIV,ISRAEL. NR 8 TC 0 Z9 0 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0108-7673 J9 ACTA CRYSTALLOGR A JI Acta Crystallogr. Sect. A PD JUL 1 PY 1992 VL 48 BP 418 EP 423 DI 10.1107/S010876739101156X PN 4 PG 6 WC Chemistry, Multidisciplinary; Crystallography SC Chemistry; Crystallography GA JF299 UT WOS:A1992JF29900003 ER PT J AU ALLEN, JP FADEN, V RAWLINGS, R AF ALLEN, JP FADEN, V RAWLINGS, R TI RELATIONSHIP OF DIAGNOSTIC, DEMOGRAPHIC, AND PERSONALITY-VARIABLES TO SELF-REPORTED STIMULI FOR CHEMICAL USE SO ADDICTIVE BEHAVIORS LA English DT Article ID ALCOHOL; RELAPSE AB While extensive research has been conducted to determine internal and external stimuli for drinking by alcoholics, the topic of how demographic, diagnostic, and personality variables may relate to these precipitants is largely unexplored. This study suggests that stimuli to use alcohol or drugs differ partly as a function of diagnosis (alcohol dependence vs. concurrent alcohol and drug dependence). Age, education, and gender do not appear related to the stimuli in either diagnostic group. Personality characteristics of cognitive reflectiveness, impulse control, sociability, and intrapunitiveness, however, seem to be associated with certain classes of high risk stimuli. RP ALLEN, JP (reprint author), NIAAA,DIV CLIN & PREVENT RES,TREATMENT RES BRANCH,ROOM 14C-20,PARKLAWN BLDG,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 21 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD JUL-AUG PY 1992 VL 17 IS 4 BP 359 EP 366 DI 10.1016/0306-4603(92)90041-S PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA HZ905 UT WOS:A1992HZ90500006 PM 1502969 ER PT J AU MORSE, HC CHATTOPADHYAY, SK MAKINO, M FREDRICKSON, TN HUGIN, AW HARTLEY, JW AF MORSE, HC CHATTOPADHYAY, SK MAKINO, M FREDRICKSON, TN HUGIN, AW HARTLEY, JW TI RETROVIRUS-INDUCED IMMUNODEFICIENCY IN THE MOUSE - MAIDS AS A MODEL FOR AIDS SO AIDS LA English DT Editorial Material DE IMMUNODEFICIENCY; AIDS; MAIDS; MURINE LEUKEMIA VIRUS ID MURINE LEUKEMIA VIRUSES; LONG-TERM DEPLETION; T-CELL RESPONSES; C57BL/6 MICE; INTERFERON-GAMMA; LYMPHOCYTES-T; RADLV-RS; FELINE LEUKEMIA; INFECTION; INDUCTION C1 NIAID,IMMUNOPATHOL LAB,BETHESDA,MD 20892. OI Morse, Herbert/0000-0002-9331-3705 NR 80 TC 240 Z9 240 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD JUL PY 1992 VL 6 IS 7 BP 607 EP 621 DI 10.1097/00002030-199207000-00001 PG 15 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA JB689 UT WOS:A1992JB68900001 PM 1503680 ER PT J AU MOORE, RD KERULY, J RICHMAN, DD CREAGHKIRK, T CHAISSON, RE BARTLETT, J LINK, G MCAVINUE, S BRYSON, Y COHEN, H FISCHL, M BOLIN, T KESSLER, H BURROUGH, Y MILDVAN, D FOX, A RICHMAN, D FREEMAN, B SIMON, G GRABOWY, KW CHERNOFF, D DUFF, P THOMPSON, S BARRETT, K AWE, R CHAPMAN, R LEONARD, S TURNER, P HAWKINS, M MURRAY, H BOWERS, J TILSON, HH ANDREWS, E SMILEY, L LANE, C AF MOORE, RD KERULY, J RICHMAN, DD CREAGHKIRK, T CHAISSON, RE BARTLETT, J LINK, G MCAVINUE, S BRYSON, Y COHEN, H FISCHL, M BOLIN, T KESSLER, H BURROUGH, Y MILDVAN, D FOX, A RICHMAN, D FREEMAN, B SIMON, G GRABOWY, KW CHERNOFF, D DUFF, P THOMPSON, S BARRETT, K AWE, R CHAPMAN, R LEONARD, S TURNER, P HAWKINS, M MURRAY, H BOWERS, J TILSON, HH ANDREWS, E SMILEY, L LANE, C TI NATURAL-HISTORY OF ADVANCED HIV DISEASE IN PATIENTS TREATED WITH ZIDOVUDINE SO AIDS LA English DT Article DE NATURAL HISTORY; ZIDOVUDINE; OPPORTUNISTIC INFECTION; EPIDEMIOLOGY ID IMMUNODEFICIENCY VIRUS TYPE-1; SAN-FRANCISCO; AIDS; INFECTION; SURVIVAL; EXPERIENCE; FOLLOW; MEN AB Objective: To describe the natural history of advanced HIV disease in patients treated with zidovudine. Design: Longitudinal, observational study. Setting: Twelve academic and community-based sites. Patients, participants: Eight hundred and sixty-three patients with AIDS or AIDS-related complex (ARC) with a CD4+ lymphocyte count < 250 x 10(6)/l, who first received zidovudine between 15 April 1987 and 14 April 1988. Main outcome measures: Survival, progression to AIDS and first development of specific opportunistic illness. Results: Median survival after initiation of zidovudine therapy ranged from > 900 days in patients with a baseline CD4+ lymphocyte count greater-than-or-equal-to 150 x 10(6)/l to 560 days in patients with a CD4+ lymphocyte count < 50 x 10(6)/1. Other factors associated significantly with poorer survival were diagnosis of AIDS (versus ARC), baseline age greater-than-or-equal-to 40 years, hematocrit < 35%, and diminished functional status. In patients with ARC at enrollment, median time of progression to AIDS ranged from 810 days in patients with a CD4+ lymphocyte count greater-than-or-equal-to 150 x 10(6)/l to 310 days in patients with a CD4+ lymphocyte count < 50 x 10(6)/l. Rates of development of specific opportunistic infections or neoplasms and HIV encephalopathy were determined for different baseline CD4+ lymphocyte count ranges. Myelosuppression was significantly more common in patients with CD4+ lymphocyte counts greater-than-or-equal-to 100 x 10(6)/l. Sixty-five per cent of patients with a CD4 + lymphocyte count greater-than-or-equal-to 100 x 10(6)/l and 51% with a CD4+ lymphocyte count < 100 x 10(6)/l continued to receive zidovudine 2 years after starting therapy. Conclusions: We describe the natural history of a cohort of patients treated with zidovudine for advanced HIV disease. These CD4+ lymphocyte count-stratified estimates of disease progression should provide prognostic information useful in the clinical management of advanced disease and the design of future studies. C1 UNIV CALIF SAN DIEGO,DEPT PATHOL,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. BURROUGHS WELLCOME CO,RES TRIANGLE PK,NC 27709. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. UNIV MIAMI,MIAMI,FL 33152. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. BETH ISRAEL MED CTR,NEW YORK,NY 10003. VET AFFAIRS MED CTR,SAN DIEGO,CA. GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. UNIV CALIF SAN FRANCISCO,AIDS CLIN,SAN FRANCISCO,CA 94143. EMORY UNIV,ATLANTA,GA 30322. LYNDON BAINES JOHNSON GEN HOSP,HOUSTON,TX. KAISER PERMANENTE MED GRP,LOS ANGELES,CA. CORNELL UNIV,MED CTR,NEW YORK,NY 10021. BURROUGHS WELLCOME CO,RES TRIANGLE PK,NC 27709. NIAID,BETHESDA,MD 20892. RP MOORE, RD (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT MED,1830 E MONUMENT ST,ROOM 8059,BALTIMORE,MD 21205, USA. NR 21 TC 52 Z9 53 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD JUL PY 1992 VL 6 IS 7 BP 671 EP 677 DI 10.1097/00002030-199207000-00009 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA JB689 UT WOS:A1992JB68900009 PM 1503686 ER PT J AU DEKABAN, GA KING, EE WATERS, D RICE, GPA AF DEKABAN, GA KING, EE WATERS, D RICE, GPA TI NUCLEOTIDE-SEQUENCE ANALYSIS OF AN HTLV-I ISOLATE FROM A CHILEAN PATIENT WITH HAM TSP SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID VIRUS TYPE-I; T-CELL LEUKEMIA; TROPICAL SPASTIC PARAPARESIS; MULTIPLE-SCLEROSIS; GENE; PROVIRUS; DNA; AMPLIFICATION; RETROVIRUSES; VARIANTS AB Isolates of HTLV-1 have been characterized from a number of different regions of the world; however, there has not been a nucleotide sequence analysis of an HTLV-I isolate from a South American country. Reported here is an individual from Chile identified with the HTLV-I-associated neurologic-al disease HAM/TSP. The sera and the nucleic acid sequence of the HTLV-I present in peripheral blood lymphocytes from this Chilean HAM/TSP patient over a two year period are characterized. During this time, the patient's condition grew progressively worse. While the serological profile of this patient was unremarkable in comparison with other HAM/TSP patients previously described, nucleic acid sequence analysis identified two nucleotide positions which contained nucleotides unique to this Chilean isolate. The nucleotide sequence analysis also indicates that the Chilean HTLV-I isolate is more closely related to Caribbean and Japanese isolates of HTLV-I than to the African and U.S. isolates described so far. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYN CORP,FREDERICK,MD 21701. UNIV WESTERN ONTARIO,UNIV HOSP,DEPT CLIN NEUROL SCI,LONDON N6A 5A5,ONTARIO,CANADA. RP DEKABAN, GA (reprint author), JOHN P ROBARTS RES INST,IMMUNOL GRP,POB 5015,100 PERTH DR,LONDON N6A 5K8,ONTARIO,CANADA. RI Dekaban, Gregory/L-1987-2013 OI Dekaban, Gregory/0000-0002-3087-4660 FU NCI NIH HHS [N01-CO-74102] NR 25 TC 25 Z9 25 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 JUL PY 1992 VL 8 IS 7 BP 1201 EP 1207 DI 10.1089/aid.1992.8.1201 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA JL627 UT WOS:A1992JL62700002 PM 1520533 ER PT J AU AOKISEI, S YARCHOAN, R KAGEYAMA, S HOEKZEMA, DT PLUDA, JM WYVILL, KM BRODER, S MITSUYA, H AF AOKISEI, S YARCHOAN, R KAGEYAMA, S HOEKZEMA, DT PLUDA, JM WYVILL, KM BRODER, S MITSUYA, H TI PLASMA HIV-1 VIREMIA IN HIV-1 INFECTED INDIVIDUALS ASSESSED BY POLYMERASE CHAIN-REACTION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS-INFECTION; AIDS-RELATED COMPLEX; BLOOD MONONUCLEAR-CELLS; PHASE-I TRIAL; MESSENGER-RNA; 2',3'-DIDEOXYINOSINE DDI; PERIPHERAL-BLOOD; QUANTITATIVE-ANALYSIS; PROVIRAL DNA; REACTION PCR AB We established a method to estimate the amounts of HIV-1 particles in plasma from patients with HIV-1 infection by using polymerase chain reaction (PCR) following reverse transcription (RT) of viral RNA (RNA-PCR) and assessed the potential usefulness of this approach to monitor the changes of viral load in patients with AIDS or AIDS-related complex (ARC) receiving 2',3'-dideoxyinosine (ddl). Plasma samples were obtained from 77 patients with HIV-1 infection (49 AIDS/ARC and 28 asymptomatic seropositives). Following ultracentrifugation of plasma, RNA was extracted from the pelleted virus and subjected to RT and PCR. The number of HIV-1 virus particles in each sample was determined using known amounts of HIV-1 DNA as reference control for PCR. The current plasma RNA-PCR technique quantitatively detected HIV-1 particles in plasma from 76 of 77 (98.7%) HIV-1-infected individuals examined. The numbers of HIV-1 particles in plasma from patients with AIDS or ARC were markedly higher than those in plasma from asymptomatic seropositive individuals (p < 0.0001). Higher levels of plasma HIV-1 particle numbers were detected in individuals with lower CD4+ T cell counts. Patients (n = 10) who received oral ddl at doses greater-than-or-equal-to 6.4 mg/kg/day for 8 to 14 weeks had a profound decrease in plasma HIV-1 particle numbers (p = 0.0051). Patients (n = 7) receiving ddl for 45 to 71 weeks also had a decrease (p = 0.018). It should be noted, however, that more research is required to evaluate the usefulness of this technique in assessing the disease status and monitoring the activity of antiretroviral therapy. C1 NCI,MED BRANCH,EXPTL RETROVIROL SECT,BLDG 10,ROOM 13N248,BETHESDA,MD 20892. NCI,CC22J,RETROVIRAL DIS SECT,BETHESDA,MD 20892. NCI,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. NR 31 TC 75 Z9 75 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 JUL PY 1992 VL 8 IS 7 BP 1263 EP 1270 DI 10.1089/aid.1992.8.1263 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA JL627 UT WOS:A1992JL62700011 PM 1520538 ER PT J AU HUNT, WA LANDS, WEM AF HUNT, WA LANDS, WEM TI A ROLE FOR BEHAVIORAL SENSITIZATION IN UNCONTROLLED ETHANOL INTAKE SO ALCOHOL LA English DT Article DE ETHANOL; SENSITIZATION; ADDICTION; ENVIRONMENTAL CUES ID LOW-DOSE ETHANOL; ADMINISTERED ETHANOL; STIMULATION AB The processes that underlie the transition from controlled to uncontrolled consumption of ethanol are unknown. Behavioral sensitization is proposed as one of these processes and occurs with repeated administration of psychomotor stimulants whereby both behavioral and neurochemical responses to the drugs are progressively enhanced. Because ethanol shares some actions in common with these drugs, chronic exposure to ethanol may intensify its reinforcing properties. The effect of ethanol on several behavioral models suggests that behavioral sensitization may develop especially in the presence of environmental cues. Thus, a research opportunity exists to study factors that contribute to an increasing probability of progressively higher ethanol consumption. Knowledge of these factors will lead to a better understanding of why some people drink uncontrollably. RP HUNT, WA (reprint author), NIAAA,DIV BASIC RES,5600 FISHERS LANE,RM 16C-05,ROCKVILLE,MD 20857, USA. NR 14 TC 58 Z9 60 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0741-8329 J9 ALCOHOL JI Alcohol PD JUL-AUG PY 1992 VL 9 IS 4 BP 327 EP 328 DI 10.1016/0741-8329(92)90075-L PG 2 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA JD742 UT WOS:A1992JD74200009 PM 1637498 ER PT J AU PIROZHKOV, SV ESKELSON, CD WATSON, RR HUNTER, GC PIOTROWSKI, JJ BERNHARD, V AF PIROZHKOV, SV ESKELSON, CD WATSON, RR HUNTER, GC PIOTROWSKI, JJ BERNHARD, V TI EFFECT OF CHRONIC CONSUMPTION OF ETHANOL AND VITAMIN-E ON FATTY-ACID COMPOSITION AND LIPID-PEROXIDATION IN RAT-HEART TISSUE SO ALCOHOL LA English DT Article DE ETHANOL; VITAMIN-E; FATTY ACID COMPOSITION; LIPID PEROXIDATION; HEART ID CHRONIC ALCOHOL INGESTION; ALPHA-TOCOPHEROL; MEMBRANE; PHOSPHOLIPIDS; TOLERANCE; OIL AB Lipid peroxidation products and the fatty acid composition of phospholipids were studied in the hearts of rats chronically consuming ethanol supplemented with large amounts of vitamin E. Ethanol representing 36% of the total calories was ingested for 7 weeks in a modified Lieber-DeCarli liquid diet that contained vitamin E at 30 IU/L in the control or 172 IU/L in the supplemental dietary group. Ethanol and/or vitamin E did not change the absolute content (mu-g per mg of phospholipids) of the main fatty acids (C18:0, C18:2, and C20:4) of heart phospholipids but increased the amount of the minor C20-C22 fatty acids. Cardiac phospholipid levels increased in rats chronically consuming excess vitamin E and/or alcohol. Chronic ethanol consumption caused elevations of the relative content (percent of total fatty acids) of tri-, tetra-, and hexaenoic acids and peroxidizability index (PI) of the cardiac phospholipids. Supplementation with vitamin E blocked this ethanol-induced shift in the fatty acid profile toward unsaturation and decreased the PI. Ethanol enhanced accumulation of vitamin E in heart tissue by 30% irrespective of the vitamin E content in the diet. Enrichment of the diet with vitamin E coincided with the low levels of fluorescent products in heart lipids. A positive correlation (r = 0.36; p = 2%) was found between vitamin E and diene conjugates in the heart cells. Thus, vitamin E has a stabilizing effect on heart phospholipids by preventing changes in their fatty acid composition and peroxidative deterioration. C1 UNIV ARIZONA,HLTH SCI CTR,NIAAA,SPECIALIZED ALCOHOL RES CTR,DEPT SURG BIOL,TUCSON,AZ 85724. MOSCOW MEDICOBIL TECHNOL ADDICT RES INST,MOSCOW 121921,USSR. UNIV ARIZONA,HLTH SCI CTR,DEPT FAMILY & COMMUNITY MED,TUCSON,AZ 85724. UNIV ARIZONA,HLTH SCI CTR,DEPT SURG,TUCSON,AZ 85724. FU NIAAA NIH HHS [NIAAA 08034] NR 32 TC 15 Z9 17 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0741-8329 J9 ALCOHOL JI Alcohol PD JUL-AUG PY 1992 VL 9 IS 4 BP 329 EP 334 DI 10.1016/0741-8329(92)90076-M PG 6 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA JD742 UT WOS:A1992JD74200010 PM 1637499 ER PT J AU VIRMANI, M AHLUWALIA, B AF VIRMANI, M AHLUWALIA, B TI BIPHASIC PROTEIN-KINASE-C TRANSLOCATION IN PC12 CELLS IN RESPONSE TO SHORT-TERM AND LONG-TERM ETHANOL EXPOSURE SO ALCOHOL AND ALCOHOLISM LA English DT Article ID NERVE GROWTH-FACTOR; CALCIUM CHANNELS; REDISTRIBUTION; MOBILIZATION; MEMBRANE; SYSTEM; CA-2+ AB Short-term and long-term effects of ethanol on protein kinase C (PKC) activity and PKC translocation from cytosol to membrane were examined in PC12 cells, a clonal cell line of neural crest origin. Treatment of PC12 cells with ethanol (30-100 mM) for 2 hr had no effect on PKC activity and PKC translocation. When PC12 cells were treated with 100 mM ethanol for 18, 44 and 74 hr, there was a biphasic effect on PKC translocation. At 18 and 44 hr ethanol treatment, PKC translocation was significantly (P < 0.001) increased, at 74 hr ethanol treatment, there was a significant decrease (P < 0.05). Less than 100 mM of ethanol had no effect on PKC activity and PKC translocation. Cyclic AMP and cyclic GMP-dependent protein kinase had no effect on PKC translocation. These findings indicate that biphasic PKC translocation from cytosol to membrane forms the basis of acute and chronic effects of ethanol on neurotransmission. C1 HOWARD UNIV,COLL MED,DEPT OBSTET & GYNECOL,ENDOCRINE RES LAB,520 W ST NW,WASHINGTON,DC 20059. NIAA,MOLEC & CELLULAR NEUROBIOL LAB,ROCKVILLE,MD 20852. NR 40 TC 10 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0735-0414 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD JUL PY 1992 VL 27 IS 4 BP 393 EP 401 PG 9 WC Substance Abuse SC Substance Abuse GA JZ243 UT WOS:A1992JZ24300010 PM 1329786 ER PT J AU COHEN, SG AF COHEN, SG TI AVICENNA ON FOOD AVERSIONS AND DIETARY PRESCRIPTIONS SO ALLERGY PROCEEDINGS LA English DT Editorial Material RP COHEN, SG (reprint author), NIAID,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1046-9354 J9 ALLERGY PROC JI Allergy Proc. PD JUL-AUG PY 1992 VL 13 IS 4 BP 199 EP 203 DI 10.2500/108854192778817194 PG 5 WC Allergy SC Allergy GA JK726 UT WOS:A1992JK72600006 PM 1427069 ER PT J AU ROBERTS, WC SHIRANI, J AF ROBERTS, WC SHIRANI, J TI THE 4 SUBTYPES OF ANOMALOUS ORIGIN OF THE LEFT MAIN CORONARY-ARTERY FROM THE RIGHT AORTIC SINUS (OR FROM THE RIGHT CORONARY-ARTERY) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Note ID PULMONARY TRUNK RP ROBERTS, WC (reprint author), NHLBI,PATHOL BRANCH,BETHESDA,MD 20892, USA. NR 6 TC 59 Z9 61 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 JUL 1 PY 1992 VL 70 IS 1 BP 119 EP 121 DI 10.1016/0002-9149(92)91406-T PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JB216 UT WOS:A1992JB21600027 PM 1615856 ER PT J AU ROBERTS, WC GLICK, BN AF ROBERTS, WC GLICK, BN TI CONGENITAL HYPOPLASIA OF BOTH RIGHT AND LEFT CIRCUMFLEX CORONARY-ARTERIES SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Note C1 GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. RP ROBERTS, WC (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 3 TC 15 Z9 16 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 JUL 1 PY 1992 VL 70 IS 1 BP 121 EP 123 DI 10.1016/0002-9149(92)91407-U PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JB216 UT WOS:A1992JB21600028 PM 1615857 ER PT J AU MARON, BJ KLUES, HG MCINTOSH, C AF MARON, BJ KLUES, HG MCINTOSH, C TI INTRAVENTRICULAR MUSCLE BAND MIMICKING ASYMMETRIC VENTRICULAR SEPTAL HYPERTROPHY AND HYPERTROPHIC CARDIOMYOPATHY SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article RP MARON, BJ (reprint author), NHLBI,CARDIOL BRANCH,BLDG 10,ROOM 7B-15,BETHESDA,MD 20892, USA. NR 6 TC 2 Z9 2 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 JUL 1 PY 1992 VL 70 IS 1 BP 130 EP 131 DI 10.1016/0002-9149(92)91411-V PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JB216 UT WOS:A1992JB21600032 PM 1615861 ER PT J AU RABKIN, CS BIGGAR, RJ MELBYE, M CURTIS, RE AF RABKIN, CS BIGGAR, RJ MELBYE, M CURTIS, RE TI 2ND PRIMARY CANCERS FOLLOWING ANAL AND CERVICAL-CARCINOMA - EVIDENCE OF SHARED ETIOLOGIC FACTORS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Note DE ANUS NEOPLASMS; CERVIX NEOPLASMS; PAPILLOMAVIRUSES; REGISTRIES; SMOKING ID INTRAEPITHELIAL NEOPLASIA; PAPILLOMAVIRUS INFECTION; LATIN-AMERICA; EPIDEMIOLOGY; PARALLEL; SMOKING AB The authors examined the incidence of second primary cancers occurring after cervical and anal cancer. Data from the Connecticut Tumor Registry for 1935-1988 and eight other US tumor registries for 1973-1988 were used. Women with primary invasive cervical cancer had a relative risk of 4.6 (95% confidence interval (Cl) 2.4-8.1) for subsequent invasive anal cancer. Increased relative risks after cervical cancer were also found for cancers of the oral cavity (relative risk (RR) = 2.2), stomach (RR = 1.5), rectum (RR = 1.4), larynx (RR = 3.4), lung (RR = 3.0), vagina (RR = 5.6), bladder (RR = 2.7), and kidney (RR = 1.9); decreased relative risks were noted for melanoma (RR = 0.5) and breast cancer (RR = 0.8). Patients with a primary diagnosis of anal cancer had relative risks for subsequent invasive and in situ cervical cancer of 1.3 (95% Cl 0.2-4.5) and 3.4 (95% Cl 0.9-8.8), respectively. Anal cancer was also associated with increased relative risks of subsequent lung (RR = 2.5) and prostate (RR = 1.8) cancers, whereas the relative risk of uterine cancer was 0.2 (95% Cl 0.0-0.9). These findings support other evidence for common factors, such as human papillomavirus infection and cigarette smoking, in the etiology of cervical and anal cancer. C1 STATE SERUM INST,DEPT EPIDEMIOL,COPENHAGEN,DENMARK. NCI,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP RABKIN, CS (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,VIRAL EPIDEMIOL SECT,EXECUT PLAZA N,ROOM 434,6130 EXECUT BLVD,ROCKVILLE,MD 20852, USA. NR 17 TC 88 Z9 88 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUL 1 PY 1992 VL 136 IS 1 BP 54 EP 58 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA JN538 UT WOS:A1992JN53800006 PM 1329500 ER PT J AU KRAMER, A BIGGAR, RJ HAMPL, H FRIEDMAN, RM FUCHS, D WACHTER, H GOEDERT, JJ AF KRAMER, A BIGGAR, RJ HAMPL, H FRIEDMAN, RM FUCHS, D WACHTER, H GOEDERT, JJ TI IMMUNOLOGICAL MARKERS OF PROGRESSION TO ACQUIRED-IMMUNODEFICIENCY-SYNDROME ARE TIME-DEPENDENT AND ILLNESS-SPECIFIC SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE BETA-2-MICROGLOBULIN; HIV ANTIBODIES; HIV ANTIGENS; HIV-1; INTERFERONS; PROPORTIONAL HAZARDS MODELS; PTERIDINES; LYMPHOCYTES-T4 ID HIV-INFECTION; PROGNOSTIC VALUE; VIRUS-INFECTION; AIDS; NEOPTERIN; SERUM; HEMOPHILIA; INTERFERON; TYPE-1; COUNT AB Since prevalent cohorts may be biased by the duration of human immunodeficiency virus (HIV) infection (onset bias), it is useful to assess the potential predictive value of markers in incident cohorts of HIV-positive subjects for whom the date of seroconversion is known or can reliably be estimated. Of 131 homosexual men with HIV-1 seroconversion from New York City and Washington, DC, who were evaluated annually beginning in 1982, 60 developed acquired immunodeficiency syndrome (AIDS) by the end of 1989. The prognostic significance of immunologic markers (proportion of CD4+ T-lymphocytes, neopterin, beta-2-Microglobulin, serum interferon, and anti-p24 antibody) and of a virologic marker (HIV p24 antigen) was determined using measurements made at defined time intervals after the known or estimated date of HIV seroconversion. When measurements made 3 years after seroconversion were used, all markers except anti-p24 antibody were found to be significant estimators of AIDS risk in univariate analyses. In multivariate Cox regression modeling, the maximum information was obtained by including neopterin, interferon, and the CD4+ T-lymphocyte proportion. The predictive value of markers after HIV seroconversion could change considerably from one interval to another. Elevated levels Of beta-2-MiCroglobulin and neopterin significantly predicted the development of Kaposi's sarcoma. These two markers were highly correlated (r = 0.74). The authors conclude that immunologic markers can be important for an HIV staging system for estimating prognosis and facilitating early therapeutic intervention in HIV-positive patients. C1 NCI,VIRAL EPIDEMIOL SECT,BLDG EPN,ROOM 434,6130 EXECUT BLVD,ROCKVILLE,MD 20852. UNIV TUBINGEN,INST MED BIOMETRY,W-7400 TUBINGEN 1,GERMANY. ABBOTT DIAGNOST PROD GMBH,W-6200 WIESBADEN,GERMANY. UNIV INNSBRUCK,INST MED CHEM & BIOCHEM,A-6020 INNSBRUCK,AUSTRIA. UNIFORMED SERV UNIV HLTH SCI,DEPT PATHOL,BETHESDA,MD 20814. FU NCI NIH HHS [N01-CP-61013] NR 26 TC 56 Z9 56 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUL 1 PY 1992 VL 136 IS 1 BP 71 EP 80 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA JN538 UT WOS:A1992JN53800008 PM 1384311 ER PT J AU ROGOT, E SORLIE, PD BACKLUND, E AF ROGOT, E SORLIE, PD BACKLUND, E TI AIR-CONDITIONING AND MORTALITY IN HOT WEATHER SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE AIR-CONDITIONING; DEMOGRAPHY; MORTALITY ID NATIONAL-DEATH-INDEX; CENSUS SAMPLES AB A cohort of 72,740 persons for whom information on household air-conditioning was available was monitored for mortality via the National Death Index from April 1980 through December 1985. A total of 2,275 deaths occurred among the members of this cohort. The basic question addressed was whether persons in households with air-conditioning experienced lower death rates during hot weather than persons in households without air-conditioning. This question was examined for both central and room air-conditioning. The analysis was based on a state-by-state approach, that cross-tabulated deaths by air-conditioning status (yes or no) and average temperature during the month of death (<21.2-degrees-C (<70-degrees-F) or greater-than-or-equal-to 21.2-degrees-C (greater-than-or-equal-to 70-degrees-F)). The Mantel-Haenszel and sign tests were used to summarize the data. For central air-conditioning versus no air-conditioning, statistically significant benefits (p<0.05, Mantel-Haenszel test) were observed for the overall total, for females, for persons not in the labor force, and for persons living in fewer than six rooms. These groups had more exposure to air-conditioning. The relative risk for the total group was 0.58, implying that in hot weather, the death rate for persons who had central air-conditioning was 42 percent lower than the rate for persons who did not have air-conditioning, after confounding variables had been controlled for. For room air-conditioning versus no air-conditioning, the odds ratio for the total group was 0.96, which was not significantly different from 1.0, suggesting that no real benefit was derived from room air-conditioning. Some reasons for the lack of a demonstrable benefit for room air-conditioning are given. C1 BUR CENSUS,DIV STAT METHODS,SUITLAND,MD. RP ROGOT, E (reprint author), NHLBI,EPIDEMIOL PROGRAM,ROOM 2C08,7550 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 17 TC 62 Z9 66 U1 0 U2 2 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUL 1 PY 1992 VL 136 IS 1 BP 106 EP 116 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA JN538 UT WOS:A1992JN53800012 PM 1415127 ER PT J AU JORDAN, E AF JORDAN, E TI THE HUMAN-GENOME-PROJECT - WHERE DID IT COME FROM, WHERE IS IT GOING SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Editorial Material RP JORDAN, E (reprint author), NIH,NATL CTR HUMAN GENOME RES,BLDG 38A,ROOM 605,BETHESDA,MD 20892, USA. NR 5 TC 22 Z9 23 U1 0 U2 1 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 JUL PY 1992 VL 51 IS 1 BP 1 EP 6 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA JA467 UT WOS:A1992JA46700001 PM 1609788 ER PT J AU WILLIAMS, RC KNOWLER, WC PETTITT, DJ LONG, JC ROKALA, DA POLESKY, HF HACKENBERG, RA STEINBERG, AG BENNETT, PH AF WILLIAMS, RC KNOWLER, WC PETTITT, DJ LONG, JC ROKALA, DA POLESKY, HF HACKENBERG, RA STEINBERG, AG BENNETT, PH TI THE MAGNITUDE AND ORIGIN OF EUROPEAN-AMERICAN ADMIXTURE IN THE GILA RIVER INDIAN COMMUNITY OF ARIZONA - A UNION OF GENETICS AND DEMOGRAPHY SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DIABETES-MELLITUS; PIMA-INDIANS AB Complementary genetic and demographic analyses estimate the total proportion of European-American admixture in the Gila River Indian Community and trace its mode of entry. Among the 9,616 residents in the sample, 2,015 persons claim only partial Native American heritage. A procedure employing 23 alleles or haplotypes at eight loci was used to estimate the proportion of European-American admixture, m(a), for the entire sample and within six categories of Caucasian admixture calculated from demographic data, m(d). The genetic analysis gave an estimate of total European-American admixture in the community of 0.054 (95% confidence interval [CI] .044-.063), while an estimate from demographic records was similar, .059. Regression of m(a) on m(d) yielded a fitted line m(a) = .922m(d), r = .959 (P = .0001). When total European-American admixture is partitioned between the contributing populations, Mexican-Americans have provided .671, European-Americans .305, and African-Americans .023. These results are discussed within the context of the ethnic composition of the Gila River Indian Community, the assumptions underlying the methods, and the potential that demographic data have for enriching genetic measurements of human admixture. It is concluded that, despite the severe assumptions of the mathematical methods, accurate, reliable estimates of genetic admixture are possible from allele and haplotype frequencies, even when there is little demographic information for the population. C1 BLOOD SYST INC,HISTOCOMPATIBIL LAB,SCOTTSDALE,AZ. NIDDKD,DIABET & ARTHRIT EPEDIMIOL SECT,PHOENIX,AZ. UNIV NEW MEXICO,DEPT ANTHROPOL,ALBUQUERQUE,NM 87131. UNIV MANITOBA,DEPT ANTHROPOL,WINNIPEG R3T 2N2,MANITOBA,CANADA. MEM BLOOD CTR MINNEAPOLIS,MINNEAPOLIS,MN. UNIV COLORADO,DEPT ANTHROPOL,BOULDER,CO 80309. CASE WESTERN RESERVE UNIV,DEPT BIOL,CLEVELAND,OH 44106. RP WILLIAMS, RC (reprint author), ARIZONA STATE UNIV,DEPT ANTHROPOL,TEMPE,AZ 85287, USA. NR 29 TC 33 Z9 35 U1 0 U2 1 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 JUL PY 1992 VL 51 IS 1 BP 101 EP 110 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA JA467 UT WOS:A1992JA46700011 PM 1609790 ER PT J AU STRIKER, GE HIRSCHMAN, GH ANDERSON, A EDINGTON, B NORWOOD, E KLAHR, S LEVEY, AS STEINMAN, T ROSA, R JOHNSON, A UNDERHILL, M PEARLSTEIN, G CHOLAKOS, B BRENNER, BM MITCH, WE SEIFTER, J LAZARUS, JM HESTER, N WETSTEIN, L DESMOND, M KOPPLE, JD ADLER, S DICHIRO, J MCKAY, SM WALSER, M WALKER, WG WARD, L BARNES, C BLAHA, C DREW, H COGGINS, CH GRONICH, J CORNELL, B MENGERT, T HUGGINS, N LEVEY, AS DWYER, J PERRONE, RD SHAH, BV LAWLOR, M STOLLAR, C RAIZMAN, D MARTIN, A FURLONG, D HUNSICKER, LG FREEMAN, RM BERTOLATUS, JA SNETSELAAR, L BROOKS, L KURTZMAN, D EASTIN, S CAMPBELL, C MASSRY, SG FEINSTEIN, E KAPTEIN, EM MATSUMOTO, J KIEFER, S TESCHAN, PE DIRAIMONDO, C HAKIM, R POWERS, S JONES, H BUSH, A ROGERS, NL WILLIAMS, GW BECK, GJ GASSMAN, JJ BERG, RL LEATHERMAN, JR MCPHERSON, JA FATICA, KJ DRABIK, MJ SKIBINSKI, CI KOVACS, MM HOUSER, HB PETOT, GJ HULL, AL MATHEWS, R NELSON, S HALL, PM ROLIN, HA PEXA, DS NAITO, HK DAVID, JA ERDEI, LM SOUTH, CA PROUDFIT, WL UNDERWOOD, DA JONES, EH UNGAR, JA LAIDLAW, S BLAGG, CR DENNIS, V GRIZZLE, JE HAWKINS, CM HOLLIDAY, MA MYERS, BD RUDMAN, D YOUNG, DS YOUNG, V DIRKS, JH GRANTHAM, J HARPER, AE PETERS, K STEIN, JH PELLEGRINO, ED VANYPERSELE, C BAROFSKY, I HELD, PJ AF STRIKER, GE HIRSCHMAN, GH ANDERSON, A EDINGTON, B NORWOOD, E KLAHR, S LEVEY, AS STEINMAN, T ROSA, R JOHNSON, A UNDERHILL, M PEARLSTEIN, G CHOLAKOS, B BRENNER, BM MITCH, WE SEIFTER, J LAZARUS, JM HESTER, N WETSTEIN, L DESMOND, M KOPPLE, JD ADLER, S DICHIRO, J MCKAY, SM WALSER, M WALKER, WG WARD, L BARNES, C BLAHA, C DREW, H COGGINS, CH GRONICH, J CORNELL, B MENGERT, T HUGGINS, N LEVEY, AS DWYER, J PERRONE, RD SHAH, BV LAWLOR, M STOLLAR, C RAIZMAN, D MARTIN, A FURLONG, D HUNSICKER, LG FREEMAN, RM BERTOLATUS, JA SNETSELAAR, L BROOKS, L KURTZMAN, D EASTIN, S CAMPBELL, C MASSRY, SG FEINSTEIN, E KAPTEIN, EM MATSUMOTO, J KIEFER, S TESCHAN, PE DIRAIMONDO, C HAKIM, R POWERS, S JONES, H BUSH, A ROGERS, NL WILLIAMS, GW BECK, GJ GASSMAN, JJ BERG, RL LEATHERMAN, JR MCPHERSON, JA FATICA, KJ DRABIK, MJ SKIBINSKI, CI KOVACS, MM HOUSER, HB PETOT, GJ HULL, AL MATHEWS, R NELSON, S HALL, PM ROLIN, HA PEXA, DS NAITO, HK DAVID, JA ERDEI, LM SOUTH, CA PROUDFIT, WL UNDERWOOD, DA JONES, EH UNGAR, JA LAIDLAW, S BLAGG, CR DENNIS, V GRIZZLE, JE HAWKINS, CM HOLLIDAY, MA MYERS, BD RUDMAN, D YOUNG, DS YOUNG, V DIRKS, JH GRANTHAM, J HARPER, AE PETERS, K STEIN, JH PELLEGRINO, ED VANYPERSELE, C BAROFSKY, I HELD, PJ TI THE MODIFICATION OF DIET IN RENAL-DISEASE STUDY - DESIGN, METHODS, AND RESULTS FROM THE FEASIBILITY STUDY SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE CHRONIC RENAL DISEASE; PROGRESSION OF RENAL DISEASE; CONTROLLED CLINICAL TRIAL; RENAL FUNCTION; DIET; BLOOD PRESSURE ID GLOMERULAR-FILTRATION-RATE; AMINO-ACID SUPPLEMENT; LOW-PROTEIN-DIET; DIABETIC NEPHROPATHY; SUBCUTANEOUS INJECTION; NUTRITIONAL-STATUS; KIDNEY-DISEASE; KETO ACID; FAILURE; PROGRESSION C1 CLEVELAND CLIN EDUC FDN,CENT ELECTROCARDIOG LAB,CLEVELAND,OH 44106. CLEVELAND CLIN EDUC FDN,CTR DRUG DISTRIBUT,CLEVELAND,OH 44106. UNIV CALIF LOS ANGELES,LOS ANGELES CTY HARBOR MED CTR,CENT AMINO ACID LAB,TORRANCE,CA 90509. NEW ENGLAND MED CTR,CTR CLIN,BOSTON,MA 02111. UNIV IOWA HOSP & CLIN,CTR CLIN,IOWA CITY,IA 52242. UNIV SO CALIF,CTR CLIN,LOS ANGELES,CA 90089. NIDDKD,ADM HLTH CARE FINANCING,BETHESDA,MD. NIDDKD,COMM STEERING,BETHESDA,MD. UNIV CALIF LOS ANGELES,LOS ANGELES CTY HARBOR MED CTR,CTR CLIN,TORRANCE,CA 90509. JOHNS HOPKINS UNIV HOSP,CTR CLIN,BALTIMORE,MD 21205. BETH ISRAEL HOSP,CTR CLIN,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,CTR CLIN,BOSTON,MA 02115. VANDERBILT UNIV,MED CTR,CTR CLIN,NASHVILLE,TN 37240. MASSACHUSETTS GEN HOSP,CTR CLIN,BOSTON,MA 02114. CASE WESTERN RESERVE UNIV,CTR NUTR COORDINATING,CLEVELAND,OH 44106. RP STRIKER, GE (reprint author), CLEVELAND CLIN EDUC FDN,DEPT BIOSTAT & EPIDEMIOL,CTR STUDY DATA COORDINATING,9500 EUCLID AVE,CLEVELAND,OH 44106, USA. NR 59 TC 24 Z9 24 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUL PY 1992 VL 20 IS 1 BP 18 EP 33 PG 16 WC Urology & Nephrology SC Urology & Nephrology GA JD485 UT WOS:A1992JD48500002 ER PT J AU BATISTA, MC CARTLEDGE, TP ZELLMER, AW MERINO, MJ AXIOTIS, C LORIAUX, DL NIEMAN, LK AF BATISTA, MC CARTLEDGE, TP ZELLMER, AW MERINO, MJ AXIOTIS, C LORIAUX, DL NIEMAN, LK TI DELAYED ENDOMETRIAL MATURATION INDUCED BY DAILY ADMINISTRATION OF THE ANTIPROGESTIN RU-486 - A POTENTIAL NEW CONTRACEPTIVE STRATEGY SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE RU-486; ANTIPROGESTINS; CONTRACEPTION; ENDOMETRIUM ID PROGESTERONE ANTAGONIST RU-486; LUTEAL PHASE; PLACENTAL PROTEIN-14; PLASMA PROGESTERONE; RADIOIMMUNOASSAY; IDENTIFICATION; OVULATION; WOMEN AB OBJECTIVE: Our objective was to determine if a progesterone antagonist might interdict the development of a secretory endometrium. STUDY DESIGN: Eleven normally cycling women not at risk for pregnancy received RU 486 (1 mg/day orally) or placebo throughout one menstrual cycle in a randomized, double-blind, crossover fashion. Estradiol, progesterone, and placental protein 14 were measured every 3 days; luteinizing hormone was measured until the midcycle surge was detected. An endometrial biopsy was performed on luteal phase day 7 to 9 and interpreted with Noyes' criteria. Differences between treatment groups were analyzed by the Student t test. RESULTS: RU 486 delayed ovulation, retarded endometrial maturation, and reduced peak levels of placental protein 14 without affecting gonadal steroid production. The abnormalities in endometrial morphology and function are similar to those seen in infertile women with luteal phase defects. CONCLUSION: We hypothesize that this regimen of antiprogestin administration may prevent implantation and offer a novel strategy for fertility control. C1 NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N262,BETHESDA,MD 20892. NCI,PATHOL LAB,DIV CANC BIOL & DIAG,BETHESDA,MD 20892. NIH,DEPT NURSING,WARREN GRANT MAGNUSON CLIN CTR,BETHESDA,MD 20892. NR 24 TC 62 Z9 62 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 JUL PY 1992 VL 167 IS 1 BP 60 EP 65 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA JE313 UT WOS:A1992JE31300014 PM 1442957 ER PT J AU IGNARTROWBRIDGE, D RISINGER, JI DENT, GA KOHLER, M BERCHUCK, A MCLACHLAN, JA BOYD, J AF IGNARTROWBRIDGE, D RISINGER, JI DENT, GA KOHLER, M BERCHUCK, A MCLACHLAN, JA BOYD, J TI MUTATIONS OF THE KI-RAS ONCOGENE IN ENDOMETRIAL CARCINOMA SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE ENDOMETRIAL CARCINOMA; ONCOGENE; RAS; POLYMERASE CHAIN REACTION ID NONPOLYPOSIS COLORECTAL-CANCER; EXPRESSION; ACTIVATION AB OBJECTIVE: The purpose of this study was to assess the extent of involvement of the ras oncogene in endometrial carcinoma. STUDY DESIGN: Genomic deoxyribonucleic acid from 30 samples of endometrial carcinoma was examined for point mutations in codons 12, 13, and 61 from the Ha-ras, Ki-ras, and N-ras genes by means of the polymerase chain reaction, slot-blotting, and deoxyribonucleic acid sequencing procedures. RESULTS: An apparent somatic mutation of Ki-ras codon 12 in one of 10 paraffin-embedded tumors was confirmed by deoxyribonucleic acid sequence analysis. Two of 20 frozen endometrial carcinoma specimens were also shown to contain a point mutation in Ki-ras codon 12. No correlation between ras mutation and a number of histologic or clinical parameters was observed. CONCLUSIONS: These data suggest a potential role for Ki-ras codon 12 mutations in the development of some (10%) endometrial cancers. C1 NIEHS,REPROD & DEV TOXICOL LAB,POB 12233,RES TRIANGLE PK,NC 27709. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,SCH MED,DEPT PSYCHOL,CHAPEL HILL,NC 27514. DUKE UNIV,MED CTR,DEPT OBSTET & GYNECOL,DURHAM,NC 27710. NR 22 TC 70 Z9 71 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 JUL PY 1992 VL 167 IS 1 BP 227 EP 232 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA JE313 UT WOS:A1992JE31300050 PM 1442931 ER PT J AU FRALIX, TA STEENBERGEN, C LONDON, RE MURPHY, E AF FRALIX, TA STEENBERGEN, C LONDON, RE MURPHY, E TI METABOLIC SUBSTRATES CAN ALTER POSTISCHEMIC RECOVERY IN PRECONDITIONED ISCHEMIC HEART SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE REPERFUSION; SUBSTRATES; CALCIUM ID CYTOSOLIC FREE CALCIUM; CONTRACTILE FUNCTION; RAT-HEART; WORKING HEART; F-19 NMR; C-13 NMR; REPERFUSION; MYOCARDIUM; GLUCOSE; INJURY AB The mechanisms that contribute to myocardial cell injury are not well understood. Furthermore, the ability of reperfusion conditions to modify ischemic injury is unclear. Recent studies have indicated that glucose utilization may improve ionic homeostasis. Because considerable derangement of ion concentrations occurs during ischemia, glucose utilization may be beneficial when stimulated during the reperfusion period. The effects of glycolytic vs. mitochondrial substrates on postischemic contractile function, high-energy phosphates and ion balance (intracellular Ca2+ and pH) were determined. Reperfusion conditions were compared in the "preconditioned ischemic" heart where baseline contractile recovery during reperfusion with glucose as the sole exogenous substrate was 74 +/- 5% (n = 10). Contractile recovery was determined for reperfusion with pyruvate (14 +/- 2%, n = 10), pyruvate + glucose (23 +/- 4%, n = 10), deoxyglucose + acetate (25 +/- 4%, n = 10), and lactate + glucose (60 +/- 11%, n = 10). Contractile dysfunction could not be attributed to differences in high-energy phosphate contents. Elevated levels of intracellular Ca2+ during reperfusion were, however, correlated with poor contractile function. After 20 min of reperfusion, the mean time-averaged intracellular Ca2+ values, measured with F-19-nuclear magnetic resonance of 4-fluoro-1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-loaded hearts, were 994 +/- 110 nM (glucose, n = 5), 2,270 +/- 494 nM (pyruvate, n = 5), 2,671 +/- 419 nM (pyruvate + glucose, n = 5), 2,382 +/- 480 nM (deoxyglucose + acetate, n = 5), and 1,019 +/- 33 nM (lactate + glucose, n = 5). These results are consistent with a beneficial role for glucose utilization during reperfusion, where enhanced recovery of contractile function and ionic homeostasis were observed. C1 DUKE UNIV,DEPT PATHOL,DURHAM,NC 27710. RP FRALIX, TA (reprint author), NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709, USA. FU NHLBI NIH HHS [R01 HL039752] NR 40 TC 17 Z9 17 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 JUL PY 1992 VL 263 IS 1 BP C17 EP C23 PN 1 PG 7 WC Physiology SC Physiology GA JF319 UT WOS:A1992JF31900002 PM 1636676 ER PT J AU GARVIN, JL SPRING, KR AF GARVIN, JL SPRING, KR TI REGULATION OF APICAL MEMBRANE ION-TRANSPORT IN NECTURUS GALLBLADDER SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE CELL VOLUME; COTRANSPORT; PARALLEL EXCHANGE; ADENOSINE 3',5'-CYCLIC MONOPHOSPHATE; ADENOSINE 3',5'-CYCLIC MONOPHOSPHOROTHIOATE, RP ISOMER ID NA+-H+; CL--HCO3 EXCHANGE; VOLUME REGULATION; EPITHELIUM; MECHANISMS; CL; SODIUM; CELLS; ENTRY; PH AB Na and Cl movement through the apical membrane of Necturus gallbladder epithelium was investigated using electrophysiological and light microscopic measurements. Changes in membrane potential difference, fractional resistance of the apical membrane, and transepithelial resistance caused by changes in apical bath Cl concentration revealed the presence of a Cl conductance in the apical membrane of control tissues that was apparently not present in the preparations studied by other investigators. This Cl conductance was blocked by bumetanide (10(-5) M) or by the inhibitor of adenosine 3',5'-cyclic monophosphate (cAMP) action, the Rp isomer of adenosine 3',5'-cyclic monophosphorothioate (Rp-cAMPS; 0.5 mM). Treatment of the tissues with Rp-cAMPS also eliminated bumetanide-sensitive cell swelling in the presence of ouabain and activated an amiloride-sensitive swelling, changes consistent with inhibition of NaCl cotransport and the activation of Na-H and Cl-HCO3 exchange. We conclude that the mode of NaCl entry into Necturus gallbladder epithelial cells is determined by the level of cAMP. When cAMP levels are high, entry occurs by NaCl cotransport; when cAMP levels are low, parallel exchange of Na-H and Cl-HCO3 predominates. These observations explain the previous disagreements about the mode of NaCl entry into Necturus gallbladder epithelial cells. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BLDG 10,RM 6N309,BETHESDA,MD 20892. NR 34 TC 8 Z9 8 U1 0 U2 0 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 JUL PY 1992 VL 263 IS 1 BP C187 EP C193 PN 1 PG 7 WC Physiology SC Physiology GA JF319 UT WOS:A1992JF31900023 PM 1322040 ER PT J AU FLESSNER, MF DEDRICK, RL REYNOLDS, JC AF FLESSNER, MF DEDRICK, RL REYNOLDS, JC TI BIDIRECTIONAL PERITONEAL TRANSPORT OF IMMUNOGLOBULIN IN RATS - TISSUE CONCENTRATION PROFILES SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE MONOCLONAL ANTIBODY; INTERSTITIUM; DIFFUSION; CONVECTION; QUANTITATIVE AUTORADIOGRAPHY ID INTERSTITIAL SPACE; ABSORPTION; RABBIT; MUSCLE; SHEEP AB Protein transport occurs between the blood and the peritoneal cavity during clinical procedures, but events within the surrounding tissue space are poorly understood. We used quantitative autoradiography to examine the tissue concentration profiles of immunoglobulin G (IgG) in regions surrounding the peritoneal cavity. We have varied the route of administration (intravenous or intraperitoneal), the osmolality of the dialysis solution (isotonic or hypertonic), and the time of analysis (20 or 200 min). After intravenous injection, IgG profiles were relatively flat in most tissues and were not affected by time or osmolality. Concentrations corresponded to the capillary density in specific tissues. After intraperitoneal administration, the IgG tissue profiles were significantly steeper than after intravenous administration. The tissue concentrations increased with time but decreased when a hypertonic solution was substituted for an isotonic solution. Hypertonic dialysis causes a water flux into the cavity, which dilutes the contents but does not prevent penetration of protein into the surrounding tissue. Based on IgG movement in tissue during hypertonic dialysis, the peritoneum appears to function as a heterogeneous structure, which allows osmotically induced water transport into the cavity in some regions with simultaneous transport of hydrostatic pressure-driven water and solute flow from the cavity into the tissue in other regions. C1 NIH,DEPT NUCL MED,BETHESDA,MD 20892. RP FLESSNER, MF (reprint author), NHLBI,NATL CTR RES RESOURCES,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892, USA. NR 22 TC 25 Z9 25 U1 0 U2 0 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 JUL PY 1992 VL 263 IS 1 BP F15 EP F23 PN 2 PG 9 WC Physiology SC Physiology GA JF321 UT WOS:A1992JF32100076 PM 1636739 ER PT J AU BLANK, PS SILVERMAN, HS CHUNG, OY HOGUE, BA STERN, MD HANSFORD, RG LAKATTA, EG CAPOGROSSI, MC AF BLANK, PS SILVERMAN, HS CHUNG, OY HOGUE, BA STERN, MD HANSFORD, RG LAKATTA, EG CAPOGROSSI, MC TI CYTOSOLIC PH MEASUREMENTS IN SINGLE CARDIAC MYOCYTES USING CARBOXY-SEMINAPHTHORHODAFLUOR-1 SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Note DE HYDROGEN; FLUORESCENCE; MUSCLE ID INTRACELLULAR PH; BCECF FLUORESCENCE; HEART-MITOCHONDRIA; RAT-HEART; FURA-2; ADULT; CALIBRATION; CALCIUM; MUSCLE; CELLS AB This study examines the use of carboxy-seminaphthorhodafluor-1 (C-SNARF-1) as an indicator of cytosolic pH in isolated rat cardiac myocytes. The emission spectrum of C-SNARF-1 when excited at 530 nm contains two well-separated peaks at approximately 590 and 640 nm, corresponding to the acidic and basic forms of the indicator. This spectral feature allows the indicator to be used in the single excitation, dual emission ratio mode. When C-SNARF-1 is loaded into rat cardiac myocytes as the membrane permeant ester derivative, C-SNARF-1/AM, the indicator localizes within the cytosol with virtually no partitioning into the mitochondria. C-SNARF-1 does not load into isolated mitochondria in suspension. There was no evidence for the presence of nondeesterified C-SNARF-1 within the cells. C-SNARF-1 can be calibrated in situ using a technique that abolishes all transsarcolemmal pH gradients. A 0.7-unit shift in the apparent pK (pK(app) = pK - log10) between the in vitro calibration and the in situ calibration is consistent with a change in beta(I640 at pH 9/I640 at pH 5) in the cytosolic environment (beta(in situ)/beta(in vitro) = 0.21) and not a change in the true pK of the indicator. The contribution of cellular autofluorescence to the total signal can be made negligible. There is no effect of C-SNARF-1 on the contractile properties of rat cardiac myocytes. The resting cytosolic pH of myocytes maintained in a nonbicarbonate buffer of N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) showed a large alkalotic shift compared with cells maintained in a bicarbonate buffer [7.48 +/- 0.17 (n = 35) in HEPES vs. 7.14 +/- 0.12 (n = 54) in bicarbonate buffer systems (mean +/- SD)]. C-SNARF-1 is well retained, and steady-state pH and transient changes in pH are easily monitored using a time-resolved fluorescence microscope system. C1 JOHNS HOPKINS MED INST,DEPT MED,DIV CARDIOL,BALTIMORE,MD 21205. JOHNS HOPKINS MED INST,DEPT ANESTHESIOL,BALTIMORE,MD 21205. RP BLANK, PS (reprint author), NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 25 TC 58 Z9 58 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 JUL PY 1992 VL 263 IS 1 BP H276 EP H284 PN 2 PG 9 WC Physiology SC Physiology GA JF321 UT WOS:A1992JF32100039 PM 1636765 ER PT J AU LINDSBERG, PJ JACOBS, TP FRERICHS, KU HALLENBECK, JM FEUERSTEIN, GZ AF LINDSBERG, PJ JACOBS, TP FRERICHS, KU HALLENBECK, JM FEUERSTEIN, GZ TI LASER-DOPPLER FLOWMETRY IN MONITORING REGULATION OF RAPID MICROCIRCULATORY CHANGES IN SPINAL-CORD SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Note DE AUTOREGULATION; ISCHEMIA; RABBIT; BLOOD FLOW ID CEREBRAL BLOOD-FLOW; RAT ISOLATED AORTA; STROKE MODEL; ISCHEMIA; AUTOREGULATION; ANESTHESIA; PRESSURE; REMOVAL; RABBIT; DOGS AB We established a rabbit model for continuous on-line monitoring of spinal cord microcirculation using laser-Doppler flowmetry (LDF). We tested the suitability of this model for studying rapid, nonequilibrium microcirculatory blood flow (BF) states induced by pharmacological treatments, hemorrhage, and asphyxia. Effective BF regulation was observed at systemic arterial pressure levels of 50 mmHg. Autoregulatory vasodilation began 1 min after the onset of severe hypotension, whereas more immediate vasodilation took place after asphyxia (hypercarbia). Pathological situations were studied in a simple model of spinal cord (SC) ischemia-reperfusion after 10 (n = 7) and 25 min (n = 7) of ischemia and 2 h of reperfusion. After 25 min of ischemia, delayed hypoperfusion (BF -35 +/- 7%, P < 0.01) took place in association with tissue edema. LDF offered sensitive, stable, and reproducible estimates of microcirculation with high temporal resolution, thus permitting on-line evaluation of rapid, nonequilibrium BF responses and delayed states of spinal cord BF dysregulation. C1 SMITH KLINE BEECHAM,KING OF PRUSSIA,PA 19406. UNIFORMED SERV UNIV HLTH SCI,F EDWARD HEBERT SCH MED,DEPT NEUROL,BETHESDA,MD 20814. NIH,STROKE BRANCH,BETHESDA,MD 20892. UNIV HELSINKI,DEPT NEUROL,HAARTMANINKATU 4,SF-00290 HELSINKI 29,FINLAND. RI Lindsberg, Perttu/F-1271-2010 FU NIGMS NIH HHS [GM-9229] NR 33 TC 25 Z9 25 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 JUL PY 1992 VL 263 IS 1 BP H285 EP H292 PN 2 PG 8 WC Physiology SC Physiology GA JF321 UT WOS:A1992JF32100040 PM 1636766 ER PT J AU SALIVE, ME AF SALIVE, ME TI THE PRACTICE AND EARNINGS OF PREVENTIVE MEDICINE PHYSICIANS SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article AB A shortage of preventive medicine (PM) physicians exists in the United States. Researchers know little about these physicians' earnings and practice characteristics. The American College of Preventive Medicine (ACPM) mailed a survey to all self-identified PM physicians on the American Medical Association (AMA) Physician Masterfile. A total of 3,771 (54%) responded; respondents' sex and region of residence were typical for PM physicians in general, with a slight excess of older physicians and those reporting board certification. A total of 2 664 71%) were working full time, with median earnings of $85,000 (mean $90,000). Among full-time physicians, relatively higher earnings were associated with the following characteristics: male sex; age 45 to 64 years; major source of income from clinical, business, or industrial sources, rather than governmental or academic; and PM board certification. Full-time PM physicians earned much less than office-based private practitioners in several primary care specialties in 1989. The gap in earnings between PM specialists in government positions and those in the private sector is also substantial. Both disparities may require creative solutions. RP SALIVE, ME (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,7201 WISCONSIN AVE,SUITE 3C-309,BETHESDA,MD 20892, USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUL-AUG PY 1992 VL 8 IS 4 BP 257 EP 262 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA JJ970 UT WOS:A1992JJ97000009 PM 1524863 ER PT J AU WEINBERGER, DR BERMAN, KF SUDDATH, R TORREY, EF AF WEINBERGER, DR BERMAN, KF SUDDATH, R TORREY, EF TI EVIDENCE OF DYSFUNCTION OF A PREFRONTAL-LIMBIC NETWORK IN SCHIZOPHRENIA - A MAGNETIC-RESONANCE-IMAGING AND REGIONAL CEREBRAL BLOOD-FLOW STUDY OF DISCORDANT MONOZYGOTIC TWINS SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PHYSIOLOGIC DYSFUNCTION; VENTRICULAR SIZE; RHESUS-MONKEY; CORTEX; LOCALIZATION; SPECULATION; ATTENTION; PATHOLOGY; DISEASE; MEMORY AB Objective: The authors previously reported that in monozygotic twins discordant for schizophrenia the affected twin almost invariably bad a smaller anterior pes hippocampus, measured with magnetic resonance imaging (MRI), and invariably bad less regional cerebral blood flow (rCBF) in the dorsolateral prefrontal cortex during performance of the Wisconsin Card Sorting Test. The present study was an investigation of the relationship between hippocampal pathology and prefrontal hypofunction in the same twin pairs. Method: Nine pairs of monozygotic twins discordant for schizophrenia underwent MRI scanning for determination of anterior hippocampal volume and xenon-inhalation rCBF testing for determination of prefrontal physiological activation associated with the Wisconsin Card Sorting Test. Results: The differences within twin pairs on the MRI and rCBF measures were strongly and selectively correlated. Specifically, the more an affected twin differed from the unaffected twin in left hippocampal volume, the more they differed in prefrontal physiological activation during the Wisconsin Card Sorting Test. In the affected twins as a group, prefrontal activation was strongly related to both left and right hippocampal volume. These relationships were not found in the group of unaffected twins. Conclusions: This finding is consistent with the notion that schizophrenia involves pathology of and dysfunction within a widely distributed neocortical-limbic neural network that has been implicated in, among other activities, the performance of cognitive tasks requiring working memory. RP WEINBERGER, DR (reprint author), ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032, USA. FU NIMH NIH HHS [MH-41176] NR 47 TC 535 Z9 540 U1 2 U2 15 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 JUL PY 1992 VL 149 IS 7 BP 890 EP 897 PG 8 WC Psychiatry SC Psychiatry GA JB015 UT WOS:A1992JB01500006 PM 1609867 ER PT J AU GERACIOTI, TD LIDDLE, RA ALTEMUS, M DEMITRACK, MA GOLD, PW AF GERACIOTI, TD LIDDLE, RA ALTEMUS, M DEMITRACK, MA GOLD, PW TI REGULATION OF APPETITE AND CHOLECYSTOKININ SECRETION IN ANOREXIA-NERVOSA SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Note ID BULIMIA-NERVOSA; SATIETY; RECEPTORS; HUNGER AB Six patients with anorexia nervosa, the same patients after weight normalization, and six healthy control subjects had similar fasting and postprandial plasma cholecystokinin concentrations. These data do not support the hypothesis that low levels of hunger and food intake in anorexic patients reflect hypersecretion of this endogenous hormone, which is thought to inhibit hunger, promote satiety, and reduce feeding. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. RI Demitrack, Mark/I-7697-2013 FU NIDDK NIH HHS [DK-38626] NR 10 TC 28 Z9 28 U1 2 U2 2 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 JUL PY 1992 VL 149 IS 7 BP 958 EP 961 PG 4 WC Psychiatry SC Psychiatry GA JB015 UT WOS:A1992JB01500018 PM 1609878 ER PT J AU ZAHM, SH WEISENBURGER, DD BABBITT, PA SAAL, RC VAUGHT, JB BLAIR, A AF ZAHM, SH WEISENBURGER, DD BABBITT, PA SAAL, RC VAUGHT, JB BLAIR, A TI USE OF HAIR COLORING PRODUCTS AND THE RISK OF LYMPHOMA, MULTIPLE-MYELOMA, AND CHRONIC LYMPHOCYTIC-LEUKEMIA SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID PARAFFIN-EMBEDDED TISSUE; CANCER; EXPOSURE; DYES; CARCINOGENICITY; COSMETOLOGISTS; HAIRDRESSERS; BEAUTICIANS; MICE; BIAS AB Objectives. Hair coloring products are widely used and contain components that are mutagenic and carcinogenic. An association between occupational exposure to hair coloring products and hematopoietic cancers has been reported, but the risk for these cancers among users has not been carefully evaluated. Methods. We conducted a population-based, case-control study with telephone interviews from 385 non-Hodgkin's lymphoma cases, 70 Hodgkin's disease cases, 72 multiple myeloma cases, 56 chronic lymphocytic leukemia cases, and 1432 controls. Results. Among women, use was associated with odds ratios of 1.5 for non-Hodgkin's lymphoma, 1.7 for Hodgkin's disease, 1.8 for multiple myeloma, and 1.0 for chronic lymphocytic leukemia. Risk was higher for permanent hair coloring products than for semi- or nonpermanent products, particularly for dark colors. Long duration and early age of first use tended to increase risk, but the patterns were inconsistent. Use was much less common in men and did not significantly increase risk. Conclusions. The use of hair coloring products appears to increase the risk of non-Hodgkin's lymphoma. Multiple myeloma and Hodgkin's disease were also associated, although based on far fewer subjects. If these results represent a causal association, use of hair coloring products would account for 35% of non-Hodgkin's lymphoma cases in exposed women and 20% in all women. C1 UNIV NEBRASKA,MED CTR,EPPLEY INST RES CANC & ALLIED DIS,OMAHA,NE 68105. WESTAT CORP,ROCKVILLE,MD. UNIV NEBRASKA,MED CTR,DEPT PATHOL & MICROBIOL,OMAHA,NE 68105. RP ZAHM, SH (reprint author), NCI,OCCUPAT STUDIES SECT,EXECUT PLAZA N,ROOM 418,ROCKVILLE,MD 20892, USA. RI Zahm, Shelia/B-5025-2015 NR 48 TC 101 Z9 104 U1 2 U2 6 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 1992 VL 82 IS 7 BP 990 EP 997 DI 10.2105/AJPH.82.7.990 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA JB539 UT WOS:A1992JB53900010 PM 1609918 ER PT J AU BERNACKI, SH NERVI, C VOLLBERG, TM JETTEN, AM AF BERNACKI, SH NERVI, C VOLLBERG, TM JETTEN, AM TI HOMEOBOX 1.3 EXPRESSION - INDUCTION BY RETINOIC ACID IN HUMAN BRONCHIAL FIBROBLASTS SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID EMBRYONAL CARCINOMA-CELLS; CENTRAL-NERVOUS-SYSTEM; GROWTH FACTOR-I; EPITHELIAL-CELLS; DIFFERENTIAL EXPRESSION; BASEMENT-MEMBRANE; RECEPTOR; LUNG; PROTEIN; INSULIN AB Homeobox (Hox) genes code for transcriptional factors and are expressed during many developmental and differentiative processes. In this study, we describe the induction of Hox 1.3 expression by retinoic acid (RA) in human bronchial fibroblasts (HBF) derived from explants of bronchial tissue. Using Northern blot analysis, we show that RA induces Hox 1.3 mRNA 3- to 10-fold over steady-state levels within 2 h after addition of RA to HBF culture medium. The induction was dose dependent, reaching a half-maximal level at approximately 10(-8) M RA. This induction was not seen in human dermal fibroblasts. Immunofluorescent staining of HBF showed a corresponding increase in Hox 1.3 protein levels in the nuclei. The increase in Hox 1.3 transcript levels in HBF was not abolished by cycloheximide treatment, suggesting that synthesis of a protein intermediate is not required for the induction. RA did not significantly alter the rate of degradation of the Hox 1.3 mRNA as determined by actinomycin D treatment, suggesting that the increase in Hox 1.3 mRNA may be due to an increase in the rate of transcription. This study provides further evidence that bronchial fibroblasts are targets for RA. Although downstream target genes for Hox 1.3 have not yet been identified, it is likely that the induction of Hox 1.3 by RA is an early step in a cascade of RA-induced changes in gene expression in bronchial fibroblasts. C1 NIEHS,PULM PATHOBIOL LAB,CELL BIOL SECT,POB 12233,RES TRIANGLE PK,NC 27709. OI Jetten, Anton/0000-0003-0954-4445; NERVI, Clara/0000-0001-9341-0188 NR 41 TC 14 Z9 15 U1 0 U2 0 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 JUL PY 1992 VL 7 IS 1 BP 3 EP 9 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA JC659 UT WOS:A1992JC65900002 PM 1627335 ER PT J AU VOLLBERG, TM GEORGE, MD NERVI, C JETTEN, AM AF VOLLBERG, TM GEORGE, MD NERVI, C JETTEN, AM TI REGULATION OF TYPE-I AND TYPE-II TRANSGLUTAMINASE IN NORMAL HUMAN BRONCHIAL EPITHELIAL AND LUNG-CARCINOMA CELLS SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID HUMAN EPIDERMAL-KERATINOCYTES; TRANSFORMING GROWTH-FACTOR; SQUAMOUS DIFFERENTIATION; RETINOIC ACID; TISSUE TRANSGLUTAMINASE; INVITRO; BETA; SUBSTRATUM; ACTIVATION; INDUCTION AB In cultured, undifferentiated normal human bronchial epithelial (HBE) cells, transglutaminase activity was localized predominantly in the cytosolic fraction of cell lysates. Upon squamous differentiation, this cytosolic activity declined and was replaced by a 40-fold increase in the activity of particulate (membrane-associated) transglutaminase. Immunoblot analysis demonstrated that the cytosolic transglutaminase was Type II (tissue) transglutaminase and that squamous differentiation shifted gene expression to the Type I (epidermal) transglutaminase. Retinoic acid, an inhibitor of squamous cell differentiation, suppressed the increase in Type I transglutaminase. The decrease in Type II transglutaminase activity was unaffected by retinoic acid. Transforming growth factor-beta-1 (TGF-beta-1) enhanced Type II transglutaminase activity about 10-fold in the undifferentiated cells but did not increase Type I transglutaminase or cholesterol sulfate, two early markers of squamous differentiation. TGF-beta-2 was equivalent to TGF-beta-1 in inducing Type II transglutaminase and in inhibiting the growth of HBE cells. The differentiation-related and TGT-beta-induced changes in transglutaminase activity were reflected in the level of transglutaminase Type I and Type II protein and mRNA. Expression of transglutaminases in lung carcinoma cell lines was variable. No correlation was observed between the expression of Type I transglutaminase and the classification of the cells as squamous cell carcinoma. Several lung carcinoma cell lines exhibited high levels of Type II transglutaminase activity that were increased several-fold by TGF-beta-1 treatment. Retinoic acid was ineffective in altering transglutaminase expression in most cell lines but induced Type II transglutaminase in a time- and dose-dependent manner in NCI-HUT-460 cells. Our results demonstrate that expression of transglutaminases is differentially regulated during squamous differentiation of HBE cells and that TGF-beta and retinoic acid can affect the expression of transglutaminases in normal and neoplastic epithelial cells derived from the human airways. C1 NIEHS,PULM PATHOBIOL LAB,CELL BIOL SECT,POB 12233,RES TRIANGLE PK,NC 27709. OI Jetten, Anton/0000-0003-0954-4445; NERVI, Clara/0000-0001-9341-0188 NR 48 TC 29 Z9 29 U1 0 U2 0 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 JUL PY 1992 VL 7 IS 1 BP 10 EP 18 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA JC659 UT WOS:A1992JC65900003 PM 1352692 ER PT J AU SHIMIZU, T NETTESHEIM, P RAMAEKERS, FCS RANDELL, SH AF SHIMIZU, T NETTESHEIM, P RAMAEKERS, FCS RANDELL, SH TI EXPRESSION OF CELL-TYPE-SPECIFIC MARKERS DURING RAT TRACHEAL EPITHELIAL REGENERATION SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID BASAL CELLS; DIFFERENTIATION; REPOPULATION; RABBITS; GROWTH; LUNGS AB Previous studies showed that Griffonia simplicifolia I-isolectin B4 (GS I-B4) and monoclonal antibodies (mAbs) against keratin 14 labeled basal cells in the adult rat trachea while other mAbs specifically stained secretory and/or ciliated cells. We used these "cell-type-specific" markers to study cellular differentiation during tracheal epithelial regeneration. Denuded tracheal grafts were inoculated with rat tracheal epithelial cells and were implanted in syngeneic hosts. Marker expression was correlated with the appearance of morphologically defined cell.types. At 4 days, the epithelium was squamoid, one to three cell layers thick, and was apparently composed of a single morphologic cell type. Because this cell did not exhibit distinguishing features of any mature tracheal cell, we provisionally termed it the "poorly differentiated cell" (PD cell). PD cells expressed keratin 14 and GS I-B4 binding sites; they contained glycogen and had lipid droplets but did not react with secretory or ciliated cell-specific mAbs. At 7 days, areas of the epithelium were pseudostratified and secretory cell-specific markers were present at the apex of differentiating columnar cells; ultrastructurally, these cells resembled secretory cells in adult tracheas. Simultaneously, a few preciliated and ciliated cells appeared that expressed a ciliated cell-specific epitope. No cells were observed coexpressing secretory and ciliated cell markers. Basal cells also became recognizable on day 7. These expressed keratin 14 and GS I-B4 binding sites throughout the study. Newly appearing secretory and ciliated cells also expressed these two markers initially but lost them gradually as the mucociliary epithelium matured. In the tracheal graft model of epithelial regeneration, the PD cells were pivotal intermediates from which all differentiated cells developed. Basal cells continued to express the same markers as PD cells, which were gradually lost in secretory and ciliated cells as they acquired new sets of specific epitopes. C1 NIEHS,PULM PATHOBIOL LAB,POB 12233,MD D2-01,RES TRIANGLE PK,NC 27709. MIE UNIV,SCH MED,DEPT OTORHINOLARYNGOL,TSU,MIE 514,JAPAN. UNIV LIMBURG,DEPT MOLEC CELL BIOL,6200 MD MAASTRICHT,NETHERLANDS. NR 25 TC 33 Z9 33 U1 1 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JUL PY 1992 VL 7 IS 1 BP 30 EP 41 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA JC659 UT WOS:A1992JC65900005 PM 1378286 ER PT J AU BARANIUK, JN KALINER, MA BARNES, PJ AF BARANIUK, JN KALINER, MA BARNES, PJ TI LOCALIZATION OF M3-MUSCARINIC-RECEPTOR MESSENGER-RNA IN HUMAN NASAL-MUCOSA SO AMERICAN JOURNAL OF RHINOLOGY LA English DT Article ID SECRETIONS; RHINITIS; METHACHOLINE; PROTEIN; NERVE; NOSE; CAT AB Cholinergic nerves play an important part in the regulation of nasal secretions and nasal patency. In situ hybridization was used to identify the cells in human nasal mucosa that express the muscarinic m3 receptor mRNA, which codes for the M3 muscarinic receptor subtype protein. An m3 cDNA probe was biotin-labeled using terminal transferase and hybridized to tissue sections of formaldehyde- or formaldehyde/microwave irradiation-fixed human nasal mucosa. The biotinylated probe was detected using gold-labeled antibiotin antibodies with silver enhancement. Muscarinic m3 receptor mRNA was identified in all epithelial cells, both serous and mucous cells of submucosal glands, and endothelial cells of small muscular arteries, veins, and capillaries. This suggests that M3 receptors may mediate glandular secretion and vasomotor effects. M3-receptor antagonists active at these sites may reduce the glandular secretion and vasodilation that is produced by parasympathetic reflex activity in allergic and non-allergic rhinitis. C1 NIAID,ALLERG DIS SECT,BETHESDA,MD 20892. NATL HEART & LUNG INST,LONDON SW3 6LY,ENGLAND. RP BARANIUK, JN (reprint author), GEORGETOWN UNIV,LUNG BIOL LABS,3900 RESERVOIR RD,WASHINGTON,DC 20007, USA. NR 21 TC 18 Z9 18 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1050-6586 J9 AM J RHINOL JI Am. J. Rhinol. PD JUL-AUG PY 1992 VL 6 IS 4 BP 145 EP 148 DI 10.2500/105065892781874649 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA JP897 UT WOS:A1992JP89700006 ER PT J AU FEUERSTEIN, IM PLUDA, JM RAFFELD, M BARKSDALE, SK AF FEUERSTEIN, IM PLUDA, JM RAFFELD, M BARKSDALE, SK TI VISCERAL CALCIFICATIONS IN PATIENTS WITH AIDS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter ID INFECTION C1 NIH,BETHESDA,MD 20892. RP FEUERSTEIN, IM (reprint author), GEORGETOWN UNIV,WASHINGTON,DC 20007, USA. NR 3 TC 2 Z9 2 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 1992 VL 159 IS 1 BP 222 EP 223 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JA200 UT WOS:A1992JA20000056 PM 1472194 ER PT J AU COLEMAN, EA KESSLER, LG WUN, LM FEUER, EJ AF COLEMAN, EA KESSLER, LG WUN, LM FEUER, EJ TI TRENDS IN THE SURGICAL-TREATMENT OF DUCTAL CARCINOMA INSITU OF THE BREAST SO AMERICAN JOURNAL OF SURGERY LA English DT Note ID CANCER; DCIS RP COLEMAN, EA (reprint author), NCI,APPL RES BRANCH,EXECUT PLAZA N,343M,BETHESDA,MD 20892, USA. NR 9 TC 7 Z9 7 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD JUL PY 1992 VL 164 IS 1 BP 74 EP 76 DI 10.1016/S0002-9610(05)80652-X PG 3 WC Surgery SC Surgery GA JC211 UT WOS:A1992JC21100016 PM 1320805 ER PT J AU BANKS, PM CHAN, J CLEARY, ML DELSOL, G DEWOLFPEETERS, C GATTER, K GROGAN, TM HARRIS, NL ISAACSON, PG JAFFE, ES MASON, D PILERI, S RALFKIAER, E STEIN, H WARNKE, RA AF BANKS, PM CHAN, J CLEARY, ML DELSOL, G DEWOLFPEETERS, C GATTER, K GROGAN, TM HARRIS, NL ISAACSON, PG JAFFE, ES MASON, D PILERI, S RALFKIAER, E STEIN, H WARNKE, RA TI MANTLE CELL LYMPHOMA - A PROPOSAL FOR UNIFICATION OF MORPHOLOGICAL, IMMUNOLOGICAL, AND MOLECULAR-DATA SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article ID INTERMEDIATE LYMPHOCYTIC LYMPHOMA; MALIGNANT-LYMPHOMAS; ZONE LYMPHOMA; MONOCLONAL-ANTIBODIES; CENTROCYTIC LYMPHOMA; GERMINAL CENTER; B-CELLS; DIFFERENTIATION; LEUKEMIA; MARKERS C1 NCI,HEMAPATHOL SECT,PATHOL LAB,BLDG 10,ROOM 2N 202,BETHESDA,MD 20892. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. QUEEN ELIZABETH HOSP,INST PATHOL,KOWLOON,HONG KONG. STANFORD UNIV,MED CTR,SCH MED,DEPT PATHOL,EXPTL ONCOL LAB,STANFORD,CA 94305. CHU PURPAN,HOP TOULOUSE,CENT ANAT PATHOL,PURPAN,FRANCE. UNIV HOSP ST RAPHAEL,PATHOL ONTLEEDKUNDE 2,LOUVAIN,BELGIUM. UNIV OXFORD,JOHN RADCLIFFE HOSP,NUFFIELD DEPT PATHOL,OXFORD OX3 9DU,ENGLAND. UNIV ARIZONA,DEPT PATHOL,TUCSON,AZ 85721. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,JAMES HOMER WRIGHT PATHOL LAB,BOSTON,MA 02114. UNIV COLL & MIDDLESEX SCH MED,MIDDLESEX HOSP,DEPT HISTOPATHOL,LONDON,ENGLAND. UNIV OXFORD,JOHN RADCLIFFE HOSP,DEPT HISTOPATHOL,OXFORD OX3 9DU,ENGLAND. UNIV BOLOGNA,POLICLIN S ORSOLA,IST ANAT & ISTOL PATOL,I-40126 BOLOGNA,ITALY. UNIV HOSP HELLERUP,KAS GENTOFTE,INST PATHOL,HELLERUP,DENMARK. FREE UNIV BERLIN,KLINIKUM STEGLITZ,INST PATHOL,W-1000 BERLIN 45,GERMANY. STANFORD UNIV,MED CTR,SURG PATHOL LAB,STANFORD,CA 94305. NR 44 TC 395 Z9 401 U1 1 U2 12 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUL PY 1992 VL 16 IS 7 BP 637 EP 640 DI 10.1097/00000478-199207000-00001 PG 4 WC Pathology; Surgery SC Pathology; Surgery GA JA445 UT WOS:A1992JA44500001 PM 1530105 ER PT J AU OHORI, NP YOUSEM, SA GRIFFIN, J STANIS, K STETLERSTEVENSON, WG COLBY, TV SONMEZALPAN, E AF OHORI, NP YOUSEM, SA GRIFFIN, J STANIS, K STETLERSTEVENSON, WG COLBY, TV SONMEZALPAN, E TI COMPARISON OF EXTRACELLULAR-MATRIX ANTIGENS IN SUBTYPES OF BRONCHIOLOALVEOLAR CARCINOMA AND CONVENTIONAL PULMONARY ADENOCARCINOMA - AN IMMUNOHISTOCHEMICAL STUDY SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE EXTRACELLULAR MATRIX; BASEMENT MEMBRANE; BRONCHIOLOALVEOLAR CARCINOMA; PULMONARY ADENOCARCINOMA; LUNG ID BASEMENT-MEMBRANE COLLAGEN; LAMININ RECEPTOR; BREAST-CARCINOMA; IV COLLAGENASE; CELL-CARCINOMA; TUMOR; INVASION; ENZYME; LUNG AB In contrast to the conventional pulmonary adenocarcinomas (CPAs), bronchioloalveolar carcinoma (BAC) grows predominantly by spreading along the existing alveolar septal framework. Within the BAC category, three subtypes have been identified: mucinous, nonmucinous, and sclerosing BAC. Of these, mucinous and sclerosing BACs have worse prognoses compared with nonmucinous BAC. However, the manifestation of aggressive behavior is different between the mucinous and sclerosing types of BACs. Multifocality is often produced by aerogenous spread, especially in the case of mucinous BACs. To study the differences between the BAC subtypes and the conventional pulmonary adenocarcinomas, we employed a battery of immunohistochemical stains marking the extracellular matrix architecture (laminin, collagen IV, fibronectin, and collagen III), a degradative enzyme against a basement membrane component (anti-type IV collagenase) and cellular receptors for laminin and collagen IV (alpha-2 integrin) on 16 BACs (5 mucinous, 5 nonmucinous, and 6 sclerosing) and 30 CPAs. The mucinous and nonmucinous BACs demonstrated neoplastic epithelial cells growing along a continuous basement membrane. A similar growth pattern with intact basement membrane was noted in the pefiphery of sclerosing BACs. However, in contrast to mucinous and nonmucinous BACs, all cases of sclerosing BACs showed disruption or complete absence of basement membrane components (laminin and collagen IV) around the embedded glands located centrally in the sclerotic fibrous stroma, as was seen in the basement membrane analysis of conventional adenocarcinomas. Furthermore, increased type IV collagenase activity was seen in the small centrally located embedded glands in compafison to the peripheral glands. These architectural alterations of basement membrane disruption and phenotypic expression of degradative activity may be a reflection of the invasive behavior of the sclerosing BACs and their tendency to produce lymph node metastasis. Although the mucinous BACs did not show evidence of basement membrane disruption, there was a marked increase in their levels of type IV collagenase expression along with consistently low levels of alpha-2 integrin receptor (laminin and collagen IV receptor) expression. These findings may be related to the ability of the mucinous BACs to detach from the underlying basement membrane and spread aerogenously, and is to be contrasted with the stromal infiltration and desmoplasia of sclerosing BACs and CPAs. C1 NIH,PATHOL LAB,BETHESDA,MD 20892. MAYO CLIN & MAYO FDN,DEPT LAB MED & PATHOL,ROCHESTER,MN 55905. RP OHORI, NP (reprint author), PRESBYTERIAN UNIV HOSP,DEPT PATHOL,DESOTO & OHARA ST,PITTSBURGH,PA 15213, USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 29 TC 44 Z9 44 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUL PY 1992 VL 16 IS 7 BP 675 EP 686 PG 12 WC Pathology; Surgery SC Pathology; Surgery GA JA445 UT WOS:A1992JA44500006 PM 1326898 ER PT J AU THOMAS, RE SIMPSON, WJ PERRY, LL SCHWAN, TG AF THOMAS, RE SIMPSON, WJ PERRY, LL SCHWAN, TG TI FAILURE OF INTRAGASTRICALLY ADMINISTERED YERSINIA-PESTIS CAPSULAR ANTIGEN TO PROTECT MICE AGAINST CHALLENGE WITH VIRULENT PLAGUE - SUPPRESSION OF FRACTION 1-SPECIFIC ANTIBODY-RESPONSE SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID INFECTION AB We evaluated the Yersinia pestis capsular (fraction 1 [F1]) antigen as a potential oral immunogen in mice. We found that single doses of as much as 0.4 mg of F1, administered by (ig) intubation, were unprotective and did not stimulate production of detectable levels of specific antibody. Three weekly ig doses resulted in low serum antibody levels that also did not provide protection against challenge with virulent Y. pestis. Assays of type-specific antibody following intubation and subsequent challenge with a subcutaneous inoculation of F1 revealed that the quantity of antigen intubated and the secondary IgG2a antibody levels were inversely related, suggesting the induction of tolerance to intragastrically administered F1 antigen. Transfer of spleen cells from intubated mice to F1 immune recipients failed to demonstrate suppression of specific antibody, indicating that the immune tolerance observed in intubated mice was not due to a T suppressor cell-mediated effect. The results of this study indicate that Y. pestis F1 antigen is not likely to be an efficacious immunogen for oral vaccination of mice against plague. C1 NIAID,ROCKY MT LABS,VECTORS & PATHOGENS LAB,ARTHROPOD BORNE DIS SECT,HAMILTON,MT 59840. UNIV NOTRE DAME,DEPT BIOL SCI,NOTRE DAME,IN 46556. NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. NR 18 TC 6 Z9 6 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 JUL PY 1992 VL 47 IS 1 BP 92 EP 97 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA JF669 UT WOS:A1992JF66900015 PM 1386197 ER PT J AU ZEIGER, MA SWARTZ, SE MACGILLIVRAY, DC LINNOILA, I SHAKIR, M AF ZEIGER, MA SWARTZ, SE MACGILLIVRAY, DC LINNOILA, I SHAKIR, M TI THYMIC CARCINOID IN ASSOCIATION WITH MEN SYNDROMES SO AMERICAN SURGEON LA English DT Article ID MULTIPLE ENDOCRINE ADENOMATOSIS; TUMOR; NEOPLASM AB Although carcinoid tumors in association with multiple endocrine neoplasia syndrome (MEN) has been well described, thymic carcinoid in association with MEN is extremely rare (only 23 cases in the world literature). A patient with thymic carcinoid and MEN-I was treated with surgical resection and postoperative radiation therapy, which was later followed by subtotal parathyroidectomy for hyperparathyroidism. Four years later, a symptomatic recurrence of his thymic carcinoid was resected from below his right clavicle. Six years after his original operation, the patient came to the hospital with pancreatitis, and a 5 cm, distal, pancreatic metastasis was resected. He now has symptomatic paraspinal and pleural metastases and is receiving somatostatin. Review of the world's literature shows that the majority of patients with thymic carcinoid and MEN-I are men with an average age of 37 years. Their clinical course is indolent, and surgery represents the only means of cure. Adjuvant chemotherapy and radiation therapy confer no survival advantage. The surgical decision making involved in treating a patient with thymic carcinoid and hyperparathyroidism associated with MEN is also discussed. C1 USN,NCI,DEPT PATHOL,BETHESDA,MD 20814. NATL NAVY MED CTR,DEPT SURG,BETHESDA,MD. NATL NAVY MED CTR,DEPT ENDOCRINOL,BETHESDA,MD. UNIV CONNECTICUT,CTR HLTH,DEPT SURG,FARMINGTON,CT 06032. RP ZEIGER, MA (reprint author), USN,NCI,SURG BRANCH,BLDG 10,ROOM 2B01,BETHESDA,MD 20892, USA. NR 20 TC 35 Z9 36 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 1776 PEACHTREE RD, NW., SUITE 410N, ATLANTA, GA 30309-2352 SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD JUL PY 1992 VL 58 IS 7 BP 430 EP 434 PG 5 WC Surgery SC Surgery GA JB309 UT WOS:A1992JB30900010 PM 1352092 ER PT J AU WASHKO, PW WELCH, RW DHARIWAL, KR WANG, YH LEVINE, M AF WASHKO, PW WELCH, RW DHARIWAL, KR WANG, YH LEVINE, M TI ASCORBIC-ACID AND DEHYDROASCORBIC ACID ANALYSES IN BIOLOGICAL SAMPLES SO ANALYTICAL BIOCHEMISTRY LA English DT Review ID PERFORMANCE LIQUID-CHROMATOGRAPHY; COULOMETRIC ELECTROCHEMICAL DETECTION; COLUMN REDUCTION SYSTEM; VITAMIN-C; ISOASCORBIC ACID; EXCHANGE CHROMATOGRAPHY; SENSITIVE DETERMINATION; DIKETOGULONIC ACID; HUMAN-NEUTROPHILS; ERYTHORBIC ACID RP WASHKO, PW (reprint author), NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892, USA. NR 127 TC 213 Z9 215 U1 2 U2 31 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 JUL PY 1992 VL 204 IS 1 BP 1 EP 14 DI 10.1016/0003-2697(92)90131-P PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA JB524 UT WOS:A1992JB52400001 PM 1514674 ER PT J AU MATSUMOTO, J FUHR, P NIGRO, M HALLETT, M AF MATSUMOTO, J FUHR, P NIGRO, M HALLETT, M TI PHYSIOLOGICAL ABNORMALITIES IN HEREDITARY HYPEREKPLEXIA SO ANNALS OF NEUROLOGY LA English DT Article ID STARTLE DISEASE; ACOUSTIC STARTLE; REFLEX MYOCLONUS; NEURONS; HYPEREXPLEXIA; PATTERNS; CAT AB Five patients from a kindred with hereditary hyperekplexia had physiological testing. The surface-recorded electromyographic pattern of audiogenic muscle jerks was identical to that of the normal acoustic startle reflex. Testing at graded stimulus intensities indicated an increase in the gain of the acoustic startle reflex. Nose-tap stimuli resulted in short-latency generalized electromyographic bursts that were similar to the R1 component of the blink reflex. Electrical stimulation of peripheral nerves elicited a pattern of generalized muscle jerks that was similar to that of the acoustic startle reflex. Somatosensory evoked potentials, brainstem auditory evoked potentials, and cortical auditory evoked potentials were normal. The primary physiological abnormality in hereditary hyperekplexia is widespread elevated gain of vestigial withdrawal reflexes in the brainstem and possibly the spinal cord, most likely resulting from increased excitability of reticular neurons. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR SECT,BLDG 10,ROOM 5N226,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. WAYNE STATE UNIV,CHILDRENS HOSP MICHIGAN,DETROIT,MI 48202. NR 27 TC 65 Z9 67 U1 0 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUL PY 1992 VL 32 IS 1 BP 41 EP 50 DI 10.1002/ana.410320108 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA JK416 UT WOS:A1992JK41600006 PM 1642471 ER PT J AU KITAYAMA, S SHIMADA, S UHL, GR AF KITAYAMA, S SHIMADA, S UHL, GR TI PARKINSONISM-INDUCING NEUROTOXIN MPP+ - UPTAKE AND TOXICITY IN NONNEURONAL COS CELLS EXPRESSING DOPAMINE TRANSPORTER CDNA SO ANNALS OF NEUROLOGY LA English DT Note ID BINDING; DISEASE AB Expression of a cloned dopamine transporter complementary DNA in COS cells allows these primate kidney cells to accumulate the parkinsonism-inducing neurotoxin metabolite MPP+ (1-methyl-4-phenylpyridinium) avidly, and MPP+ toxicity results. By documenting that the dopamine transporter can confer MPP+ sensitivity to nonneural cells, these results highlight the key role that this transporter could play in mechanisms underlying parkinsonism. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. RP UHL, GR (reprint author), NIDA,ADDICT RES CTR,MOLEC NEUROBIOL LAB,POB 5180,BALTIMORE,MD 21224, USA. NR 14 TC 83 Z9 85 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUL PY 1992 VL 32 IS 1 BP 109 EP 111 DI 10.1002/ana.410320120 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA JK416 UT WOS:A1992JK41600018 PM 1642464 ER PT J AU LAROCCA, RV COOPER, MR STEIN, CA KOHLER, D UHRICH, M WEINBERGER, E MYERS, CE AF LAROCCA, RV COOPER, MR STEIN, CA KOHLER, D UHRICH, M WEINBERGER, E MYERS, CE TI A PILOT-STUDY OF SURAMIN IN THE TREATMENT OF PROGRESSIVE REFRACTORY FOLLICULAR LYMPHOMAS SO ANNALS OF ONCOLOGY LA English DT Note ID MECHANISM; THERAPY; CANCER AB Ten patients with progressive follicular lymphomas (seven with follicular mixed lymphomas, three with follicular, small cleaved cell lymphomas) with clinical indications for systemic therapy received parenteral suramin. Each had failed from one to six prior chemotherapeutic regimens and three had in addition received prior radiation therapy. All had measurable disease and nine of the ten had documented bone marrow involvement at the start of therapy. Suramin was administered at an initial infusion rate of 350 mg/m2/day, which was then modified on the basis of subsequent weekly plasma suramin concentrations in order to reach a final plasma concentrations of 250-350-mu-g/ml. Treatment cycles were repeated at eight week intervals. Nine of ten patients are evaluable for response. Five of nine evaluable patients achieved a partial remission as defined by a greater than 50% decrease in the sum of the product of all measurable lesions. Sites of response include: Peripheral (five patients) and central (four patients) adenopathy, disappearance of biopsy-proven skin involvement (one patient), malignant pleural effusions (one patient) and shrinkage of an enlarged spleen (two patients). Disappearance of B symptoms occurred in the one responder with these symptoms. Response duration varied from 3 to 9 months (mean 5.6 months) with time to subsequent systemic therapy varying from 5 to 12 months (mean 8 months). Drug related toxicity included the development of polyradiculopathy (one case), liver function abnormalities (three cases), thrombocytopenia (five cases), vortex keratopathy (two cases) and bacterial infection (two cases). We conclude that suramin has significant activity against follicular lymphomas refractory to standard chemotherapy and that its precise role in the treatment of lymphoproliferative neoplasms in general warrants further investigation. C1 NIH,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. NR 11 TC 24 Z9 24 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUL PY 1992 VL 3 IS 7 BP 571 EP 573 PG 3 WC Oncology SC Oncology GA JE854 UT WOS:A1992JE85400017 PM 1498080 ER PT J AU CORSO, DM PUCINO, F DELEO, JM CALIS, KA GALLELLI, JF AF CORSO, DM PUCINO, F DELEO, JM CALIS, KA GALLELLI, JF TI DEVELOPMENT OF A QUESTIONNAIRE FOR DETECTING POTENTIAL ADVERSE DRUG-REACTIONS SO ANNALS OF PHARMACOTHERAPY LA English DT Article AB OBJECTIVE: To develop a comprehensive list of symptoms categorized by body system as part of a questionnaire for detecting potential adverse drug reactions. DATA SOURCES: A preliminary list of symptoms in lay terminology was extracted from the "Side Effects" section of all drug monographs contained in the United States Pharmacopeia Dispensing Information (USP DI) computerized database (Volume II, Advice for the Patient) using natural language processing software. The list was sorted alphabetically and duplicate terms were eliminated. Symptoms were then categorized by body system or anatomic region. A preferred term for each symptom was selected when multiple synonyms and related words were listed. Finally, all of the symptom terms were incorporated into a thesaurus from which the questionaire was derived. RESULTS: The questionnaire will be used as part of a computer-assisted interview, developed to solicit information from patients regarding their medication regimens and to systematically query them regarding the presence of salient symptoms or complaints. The computer system will eventually interface with the USP DI database to identify drugs from a patient's regimen that may be associated with adverse symptoms. The symptom thesauras will provide the link to the USP DI database. Preliminary experience with the questionnaire in a limited number of patients has been encouraging. CONCLUSIONS: The questionnaire can assist clinicians in identifying drug-related symptoms including unreported adverse clinical effects of newly marketed or investigational therapeutic agents. When the questionnaire is computerized and linked to a comprehensive database, it can be more widely used to alert healthcare providers of potential adverse drug reactions that may otherwise go undetected. C1 NIH,DIV COMP RES & TECHNOL,BLDG 12A,RM 2013,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,DEPT PHARM,BETHESDA,MD 20892. NIH,DRUG INFORMAT SERV,BETHESDA,MD 20892. NR 8 TC 26 Z9 27 U1 0 U2 1 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD JUL-AUG PY 1992 VL 26 IS 7-8 BP 890 EP 896 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JD753 UT WOS:A1992JD75300004 PM 1504394 ER PT J AU POGREBNIAK, HW HAAS, G LINEHAN, WM ROSENBERG, SA PASS, HI PUTNAM, JB MANSOUR, KA COOK, WA AF POGREBNIAK, HW HAAS, G LINEHAN, WM ROSENBERG, SA PASS, HI PUTNAM, JB MANSOUR, KA COOK, WA TI RENAL-CELL CARCINOMA - RESECTION OF SOLITARY AND MULTIPLE METASTASES SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 38TH ANNUAL MEETING OF THE SOUTHERN THORACIC SURGICAL ASSOC CY NOV 07-09, 1991 CL ORLANDO, FL SP SOC THORAC SURGEONS ID PULMONARY METASTASES; PROGNOSTIC FACTORS; NATURAL-HISTORY; MANAGEMENT; EXPERIENCE; SARCOMA; SURGERY AB Between 1985 and 1991, 23 patients underwent resection of pulmonary metastases from renal cell carcinoma, of whom 18 had previously received interleukin-2 based immunotherapies. Mean survival from exploration in all patients was 43 months. Survival after resection did not correlate with the number of nodules on preoperative tomograms, the number of nodules resected, or the disease-free interval. Patients who underwent complete resection of metastatic disease (n = 15), however, had a significantly longer survival (mean, 49 months; median not yet achieved) compared with patients with incomplete resection (median, 16 months) (p2 = 0.02). Two of the 15 patients who underwent curative resections are presently free of disease greater than 45 months after exploration. These data support surgical resection of isolated pulmonary metastatic disease from renal cell cancer. C1 NCI,THORAC ONCOL SECT,SURG BRANCH,BLDG 10,ROOM 2B07,BETHESDA,MD 20892. NCI,UROL ONCOL SECT,BETHESDA,MD 20892. NR 22 TC 62 Z9 63 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 JUL PY 1992 VL 54 IS 1 BP 33 EP 38 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA JA809 UT WOS:A1992JA80900006 PM 1610251 ER PT J AU STINSON, SF ALLEY, MC KOPP, WC FIEBIG, HH MULLENDORE, LA PITTMAN, AF KENNEY, S KELLER, J BOYD, MR AF STINSON, SF ALLEY, MC KOPP, WC FIEBIG, HH MULLENDORE, LA PITTMAN, AF KENNEY, S KELLER, J BOYD, MR TI MORPHOLOGICAL AND IMMUNOCYTOCHEMICAL CHARACTERISTICS OF HUMAN TUMOR-CELL LINES FOR USE IN A DISEASE-ORIENTED ANTICANCER DRUG SCREEN SO ANTICANCER RESEARCH LA English DT Article DE HUMAN TUMOR CELL LINES; CHARACTERIZATION; IMMUNOCYTOCHEMISTRY; ELECTRON MICROSCOPY ID MOUSE MONOCLONAL-ANTIBODIES; SURFACE-ANTIGENS; GROWTH-CHARACTERISTICS; SPECIFICITY ANALYSIS; CANCER; MELANOCYTES; CARCINOMA; CLASSIFICATION; ESTABLISHMENT; GLYCOPROTEIN AB A panel of 60 human tumor cell lines is currently being used in the U.S. National Cancer Institute's in vitro anticancer drug screen. The panel is organized into 7 subpanels; 6 leukemia/lymphoma lines comprise one subpanel, and 54 other lines are organized into subpanels representing solid tumors of the central nervous system (CNS), colon, lung, ovaries, kidneys and melanomas. In the present study, the leukemia and lymphoma cell lines were analyzed by flow cytometry for appropriate CD antigens; all but 1 line showed patterns of expression consistent with their reported derivations. The solid tumor lines were characterized individually using morphological and immunocytochemical techniques to determine their relative degrees of representativity for the subpanels within which they are currently grouped. Histological, histochemical and ultrastructural examinations were performed on cell lines grown under identical conventional culture conditions and as xenografts in nude mice. Immunocytochemistry using panels of antibodies raised against 6 types of intermediate filaments, 7 adenocarcinoma-associated antigens, 7 melanoma/neuro-ectodermal-associated antigens, 3 neuroendocrine-associated antigens, 9 urinary tract associated antigens, and 4 markers of muscle differentiation was done on cells grown in monolayer culture. Central nervous system (CNS) cell lines lacked expression of glial fibrillary acidic protein, but all ha d other features consistent with derivation from glioblastoma. Lines derived from adenocarcinomas of the colon, lung and ovary, for the most part, expressed adenocarcinoma-associated antigens and showed histological and/or ultrastructural evidence of gland formation and other adenomatous features. Most of these lines were poorly differentiated. Lines derived from large-cell and squamous-cell cancers also showed some characteristics consistent with their reported origins, except for one line which showed immunocytochemical and morphologic characteristics consistent with rhabdomyosarcoma. The 2 lines derived from small cell lung cancer (SCLC) lacked neurosecretory granules and 3 other SCLC markers but showed morhologic features consistent with SCLC. Most melanoma cell lines strongly expressed melanoma-associated antigens and were morphologically similar to human melanoma. Five lines produced premelanosomes, melanosomes or melanin. Most of the renal cancer cell lines showed morphologic or immunocytochemical features consistent with renal clear cell carcinoma. Collectively, these morphological and immunocytochemical analyses provide information concerning tissue of origin, tumor type, degree of differentiation and other biologic features essential to the use of these lines in a disease-oriented in vitro antitumor drug screen and to the interpretation of data derived therefrom. C1 FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES DYNCORP,CLIM IMMUNOL SERV,FREDERICK,MD 21702. UNIV FREIBURG,W-7800 FREIBURG,GERMANY. RP STINSON, SF (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,DRUG DISCOVERY RES & DEV LAB,BLDG 1052,ROOM 121,FREDERICK,MD 21701, USA. FU NCI NIH HHS [N01-CO-74102] NR 40 TC 101 Z9 102 U1 0 U2 2 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JUL-AUG PY 1992 VL 12 IS 4 BP 1035 EP 1054 PG 20 WC Oncology SC Oncology GA JJ238 UT WOS:A1992JJ23800001 PM 1503399 ER PT J AU MOON, RC KELLOFF, GJ DETRISAC, CJ STEELE, VE THOMAS, CF SIGMAN, CC AF MOON, RC KELLOFF, GJ DETRISAC, CJ STEELE, VE THOMAS, CF SIGMAN, CC TI CHEMOPREVENTION OF MNU-INDUCED MAMMARY-TUMORS IN THE MATURE RAT BY 4-HPR AND TAMOXIFEN SO ANTICANCER RESEARCH LA English DT Article DE CHEMOPREVENTION; MAMMARY GLANDS; TAMOXIFEN; 4-HPR; RAT ID CANCER CHEMOPREVENTION; ICI 46,474; CARCINOGENESIS; INHIBITION; INITIATION; CARCINOMA; MODEL; CELL AB The chemopreventive efficacies of the retinoid all-trans-N-(4-hydroxyphenyl)-retinamide (4-HPR) and the antiestrogen tamoxifen citrate were evaluated against N-methyl-N'-nitrosourea (MNU) induced mammary cancer in 120-day old female Sprague-Dawley rats. The agents were tested alone and in combination. They were administered in a modified AIN-76A diet, beginning 60 days prior to a single i.v. dose of 50 mg MNU/kg-bw and continuing until the end of the study, 180 days post-carcinogen treatment. At 782 mg/kg diet, 4-HPR alone significantly inhibited the induction of mammary adenocarcinomas compared with carcinogen controls. At 0.250 mg/kg diet, tamoxifen alone reduced tumor incidence compared with carcinogen controls. At 0.125 mg/kg diet, tamoxifen was ineffective. Combinations of 782 mg 4-HPR/kg diet with either 0.250 or 0.125 mg tamoxifen/kg diet were effective in inhibiting MNU-induced adenocarcinomas. The reductions in tumor incidence were greater for these combinations than for either agent alone. 4-HPR and 0.250 mg tamoxifen/kg diet decreased tumor incidence 81% (p<0.005), whereas 4-HPR and 0.125 mg tamoxifen/kg diet decreased tumor incidence 72% (p<0.005) compared with carcinogen controls. The combination of 391 mg 4-HPR/kg diet and 0.500 mg tamoxifen/kg diet was also tested and was effective in reducing tumor incidence. C1 NCI,DIV CANC PREVENT & CONTROL,CHEMOPREVENT BRANCH,FREDERICK,MD 21701. CCS ASSOCIATES,PALO ALTO,CA 94301. RP MOON, RC (reprint author), IIT,RES INST,PATHOPHYSIOL LAB,10 W 35TH ST,CHICAGO,IL 60616, USA. FU NCI NIH HHS [N01-CN-85097-04] NR 26 TC 62 Z9 63 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JUL-AUG PY 1992 VL 12 IS 4 BP 1147 EP 1154 PG 8 WC Oncology SC Oncology GA JJ238 UT WOS:A1992JJ23800014 PM 1386970 ER PT J AU METTER, EJ JACKSON, CA KEMPLER, D HANSON, WR AF METTER, EJ JACKSON, CA KEMPLER, D HANSON, WR TI TEMPOROPARIETAL CORTEX AND THE RECOVERY OF LANGUAGE COMPREHENSION IN APHASIA SO APHASIOLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; COMPUTED-TOMOGRAPHY AB Recovering aphasic patients were studied to determine if changes in comprehension were linked to improvement in temporoparietal regional glucose metabolism. Eight aphasic patients were evaluated at two points in time, using (F-18)-fluorodeoxyglucose with positron emission tomography to determine resting cerebral glucose metabolism, and by the Western Aphasia Battery (WAB) to determine language function. Significant correlations were found between changes over time of left and right temporoparietal regions with the change in the comprehension score from the WAB. The high correlations between the left and right temporoparietal metabolic rates do not allow for a conclusion as to the extent of contribution of either region to the improvement in comprehension. A single-case analysis demonstrated that a true understanding of the role of functional improvement (as measured by glucose metabolism) requires a more complex model that considers interactions between structural damage and the consequence of that damage on other brain regions. C1 VET ADM MED CTR,SEPULVEDA,CA 91343. SCH GERONTOL,LOS ANGELES,CA. UNIV SO CALIF,SCH MED,LOS ANGELES,CA 90033. RP METTER, EJ (reprint author), NIA,GERONTOL RES CTR,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 13 TC 19 Z9 20 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PD JUL-AUG PY 1992 VL 6 IS 4 BP 349 EP 358 DI 10.1080/02687039208248606 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA JG673 UT WOS:A1992JG67300003 ER PT J AU NORENBERG, JP SIMPSON, NR DUNN, BB KIESEWETTER, DO AF NORENBERG, JP SIMPSON, NR DUNN, BB KIESEWETTER, DO TI REMOTE SYNTHESIS OF [C-11] ACETATE SO APPLIED RADIATION AND ISOTOPES LA English DT Note ID POSITRON EMISSION TOMOGRAPHY; MYOCARDIAL OXIDATIVE-METABOLISM; C-11 ACETATE; OXYGEN-CONSUMPTION; PATTERNS AB This remote synthesis greatly simplifies previously reported liquid-liquid extraction techniques for remote production of [C-11]acetate. The use of solid phase extraction has reduced the total volume of solvents employed while providing [C-11]acetate free of labeled by-products. Remotely actuated loop flow valves have been utilized to efficiently and quickly introduce reagents. [C-11]Acetate is obtained within 15 min from the end of bombardment in 43% (EOB) radiochemical yield and with radiochemical purity >98%. C1 UNIV NEW MEXICO,SCH MED,COLL PHARM,ALBUQUERQUE,NM 87131. NIH,WARREN G MAGNUSON CLIN CTR,DEPT POSITRON EMISS TOMOG,BETHESDA,MD 20892. NR 10 TC 16 Z9 16 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0969-8043 J9 APPL RADIAT ISOTOPES JI Appl. Radiat. Isot. PD JUL PY 1992 VL 43 IS 7 BP 943 EP 945 PG 3 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Chemistry; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA JB796 UT WOS:A1992JB79600021 ER PT J AU UENG, TH UENG, YF PARK, SS AF UENG, TH UENG, YF PARK, SS TI COMPARATIVE INDUCTION OF CYTOCHROME-P-450-DEPENDENT MONOOXYGENASES IN THE LIVERS AND GILLS OF TILAPIA AND CARP SO AQUATIC TOXICOLOGY LA English DT Article DE CYTOCHROME-P-450; MONOOXYGENASE; INDUCTION; GILL; TILAPIA; CARP ID FISH STENOTOMUS-CHRYSOPS; RAINBOW-TROUT; HEPATIC CYTOCHROME-P-450; OREOCHROMIS-MOSSAMBICUS; MARINE TELEOST; 3-METHYLCHOLANTHRENE; PROTEINS; ISOZYMES; SCUP; BIOTRANSFORMATION AB The induction properties of liver and gill microsomal monooxygenases were determined using freshwater fish tilapia (Oreochromis mossambicus) and carp (Cyprinus carpio), which are relatively pollution resistant and nonresistant, respectively. Pretreatments with 3-methylcholanthrene (3-MC) and polychlorinated biphenyls (PCBs) markedly increased microsomal cytochrome P-450 (P-450) contents and P-450-dependent monooxygenase activities toward benzo(a)pyrene, 7-ethoxyresorufin and 7-ethoxycoumarin, in the fish tissues. In the liver, the elevated levels of benzo(a)pyrene and 7-ethoxyresorufin oxidation activities in tilapia were higher than the corresponding levels in carp. Conversely, in the gill, the elevated levels in carp were higher than or similar to tilapia. Gel electrophoresis and immunoblotting analyses of liver and gill microsomes revealed that the xenobiotic pretreatments induced specific tilapia and carp proteins recognized by the monoclonal antibody (MAb) 1-12-3 to marine fish scup P-450E, a teleost orthologue of P-450 1A1. In contrast to 3-MC and PCBs, phenobarbital (PB) failed to induce monooxygenases in the fish tissues except in carp liver where PB increased 7-ethoxycoumarin O-deethylase activity and weakly induced a protein with which MAb 1-12-3 was cross-reactive. The results of field studies showed that the hepatic levels of P450 1A1 and associated monooxygenase activities were elevated in tilapia collected from a polluted river, relative to tilapia and carp collected from nonpolluted water. C1 NATL TAIWAN UNIV,COLL MED,DEPT BIOCHEM,TAIPEI,TAIWAN. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RP UENG, TH (reprint author), NATL TAIWAN UNIV,COLL MED,INST TOXICOL,1 JEN AI RD,SECT 1,TAIPEI,TAIWAN. NR 38 TC 26 Z9 26 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-445X J9 AQUAT TOXICOL JI Aquat. Toxicol. PD JUL PY 1992 VL 23 IS 1 BP 49 EP 64 PG 16 WC Marine & Freshwater Biology; Toxicology SC Marine & Freshwater Biology; Toxicology GA JB781 UT WOS:A1992JB78100004 ER PT J AU FISHER, A TANIUCHI, H AF FISHER, A TANIUCHI, H TI A STUDY OF CORE DOMAINS, AND THE CORE DOMAIN DOMAIN INTERACTION OF CYTOCHROME-C FRAGMENT-COMPLEX SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID FERRIC APLYSIA MYOGLOBIN; CONFORMATION CHANGE; FERRICYTOCHROME-C; FERROCYTOCHROME-C; HEME FRAGMENT; RESOLUTION; APOPROTEIN; PROTEIN; ISO-1-CYTOCHROME-C; COORDINATION C1 NIDDKD, CHEM BIOL LAB, BETHESDA, MD 20892 USA. NR 53 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUL PY 1992 VL 296 IS 1 BP 1 EP 16 DI 10.1016/0003-9861(92)90538-8 PG 16 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA HY138 UT WOS:A1992HY13800001 PM 1376596 ER PT J AU OLSEN, DB HEPBURN, TW LEE, SL MARTIN, BM MARIANO, PS DUNAWAYMARIANO, D AF OLSEN, DB HEPBURN, TW LEE, SL MARTIN, BM MARIANO, PS DUNAWAYMARIANO, D TI INVESTIGATION OF THE SUBSTRATE BINDING AND CATALYTIC GROUPS OF THE P-C BOND CLEAVING ENZYME, PHOSPHONOACETALDEHYDE HYDROLASE SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID CARBON-PHOSPHORUS BOND; ACETOACETATE DECARBOXYLASE; ACTIVE-SITE; AMINO GROUP; CLEAVAGE; MECHANISM; PRODUCTS C1 UNIV MARYLAND,DEPT CHEM & BIOCHEM,COLLEGE PK,MD 20742. NIMH,CLIN NEUROSCI BRANCH,MOLEC NEUROGENET UNIT,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM-27257, GM 28688] NR 31 TC 27 Z9 28 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUL PY 1992 VL 296 IS 1 BP 144 EP 151 DI 10.1016/0003-9861(92)90556-C PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA HY138 UT WOS:A1992HY13800019 PM 1605625 ER PT J AU TANGREA, JA KILCOYNE, RF TAYLOR, PR HELSEL, WE ADRIANZA, ME HARTMAN, AM EDWARDS, BK PECK, GL AF TANGREA, JA KILCOYNE, RF TAYLOR, PR HELSEL, WE ADRIANZA, ME HARTMAN, AM EDWARDS, BK PECK, GL TI SKELETAL HYPEROSTOSIS IN PATIENTS RECEIVING CHRONIC, VERY-LOW-DOSE ISOTRETINOIN SO ARCHIVES OF DERMATOLOGY LA English DT Article ID VITAMIN-A; ANKYLOSING HYPEROSTOSIS; 13-CIS-RETINOIC ACID; SPINAL HYPEROSTOSIS; FORESTIERS DISEASE; ETRETINATE TIGASON; ROTES-QUEROL; THERAPY; DISH; CALCIFICATION AB Background and Design.-We conducted a prospective roentgenographic survey of patients participating in a randomized, placebo-controlled, multicenter clinical trial that evaluated the effectiveness of chronic, very-low-dose (approximately 0.14 mg/kg per day for 3 years) isotretinoin in preventing the subsequent occurrences of new basal cell carcinoma in patients with previous basal cell carcinoma. To assess potential skeletal changes, a sample of 269 patients from among a total of 981 enrollees were randomly selected for comparative roentgenographic review. Baseline and 36-month roentgenograms of the cervical and thoracic spine of each patient were read side by side by a radiologist, masked to treatment group, who noted both the presence and extent of abnormalities at each vertebral level at baseline and the progression of existing or occurrence of new abnormalities at previously unaffected levels at 36 months. Results.-In comparison with the placebo group, significantly more patients in the isotretinoin group exhibited progression of existing hyperostotic abnormalities (40% vs 18%; P<.001) and new hyperostotic involvement at previously unaffected vertebral levels (8% vs 1%; P=.015). Conclusion.-Our findings indicate that chronic, very-low-dose isotretinoin can induce hyperostotic axial skeletal changes similar to those reported in patients taking higher doses. C1 NCI, DIV CANC PREVENT & CONTROL, BETHESDA, MD 20892 USA. INFORMAT MANAGEMENT SERV INC, SILVER SPRING, MD USA. UNIV MARYLAND, DEPT DERMATOL, COLLEGE PK, MD 20742 USA. UNIV COLORADO, DEPT RADIOL, DENVER, CO 80202 USA. NR 34 TC 8 Z9 9 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-987X EI 1538-3652 J9 ARCH DERMATOL JI Arch. Dermatol. PD JUL PY 1992 VL 128 IS 7 BP 921 EP 925 DI 10.1001/archderm.128.7.921 PG 5 WC Dermatology SC Dermatology GA JD499 UT WOS:A1992JD49900003 ER PT J AU RAPOPORT, JL RYLAND, DH KRIETE, M AF RAPOPORT, JL RYLAND, DH KRIETE, M TI DRUG-TREATMENT OF CANINE ACRAL LICK - AN ANIMAL-MODEL OF OBSESSIVE-COMPULSIVE DISORDER SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID FENFLURAMINE; BEHAVIOR; NORFENFLURAMINE; ADOLESCENTS; SYMPTOMS; CHILDREN AB Canine acral lick dermatitis is a naturally occurring disorder in which excessive licking of paws or flank can produce ulcers and infection that require medical treatment. Forty-two dogs with severe chronic canine acral lick dermatitis were treated in three double-blind crossover comparisons of clomipramine hydrochloride/desipramine hydrochloride, fluoxetine hydrochloride/fenfluramine hydrochloride, and sertraline hydrochloride/placebo. The serotonin uptake blocking drugs were clinically effective, while the other drugs were not. Based on phenomenology and pharmacological response, we propose canine acral lick dermatitis as an animal model of obsessive-compulsive disorder. C1 NIH,CTR ANIM,POOLESVILLE,MD. RP RAPOPORT, JL (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 47 TC 135 Z9 136 U1 2 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUL PY 1992 VL 49 IS 7 BP 517 EP 521 PG 5 WC Psychiatry SC Psychiatry GA JC527 UT WOS:A1992JC52700001 PM 1385694 ER PT J AU COHEN, RM GROSS, M NORDAHL, TE SEMPLE, WE OREN, DA ROSENTHAL, N AF COHEN, RM GROSS, M NORDAHL, TE SEMPLE, WE OREN, DA ROSENTHAL, N TI PRELIMINARY DATA ON THE METABOLIC BRAIN PATTERN OF PATIENTS WITH WINTER SEASONAL AFFECTIVE-DISORDER SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL GLUCOSE-METABOLISM; OBSESSIVE-COMPULSIVE DISORDER; SCHIZOPHRENIC-PATIENTS; AFFECTIVE-ILLNESS; PANIC DISORDER; LIGHT THERAPY; RATES; DEPRESSION; CORTEX AB The brain metabolic pattern of patients with winter seasonal affective disorder with and without light treatment was determined by positron emission tomography. Compared with controls, patients with seasonal affective disorder with and without light treatment had globally lower metabolic rates, relatively lower superior medial frontal cortex rates, and somewhat higher basal ganglia rates. Patients receiving light treatment had a relatively higher rate in an occipital region of interest containing the primary visual cortex. Patients without light treatment had relatively higher metabolic rates in right parietal and medial orbitofrontal cortex and lower rates in the left parietal cortex. Patients not receiving light treatment had a hemispheric metabolic asymmetry (left greater than right) for the mid-prefrontal cortex located 67 mm above the canthomeatal line. The right side of this region, previously found reduced in manic-depressive illness and schizophrenia, was decreased primarily in patients with seasonal affective disorder with fewer atypical depressive symptoms. These "abnormal" prefrontal and parietal cortex regions appeared highly "coupled" in the patients with seasonal affective disorder. C1 NIMH,CLIN PSYCHOBIOL BRANCH,ENVIRONM PSYCHIAT SECT,BETHESDA,MD 20892. RP COHEN, RM (reprint author), NIMH,INTRAMURAL RES PROGRAM,CEREBRAL METAB LAB,BETHESDA,MD 20892, USA. RI Nordahl, Thomas/J-7643-2013 OI Nordahl, Thomas/0000-0002-8627-0356 NR 46 TC 65 Z9 65 U1 1 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 JUL PY 1992 VL 49 IS 7 BP 545 EP 552 PG 8 WC Psychiatry SC Psychiatry GA JC527 UT WOS:A1992JC52700005 PM 1627045 ER PT J AU KITTUR, SD HOH, JH KAWAS, CH HAYWARD, GS ENDO, H ADLER, WH AF KITTUR, SD HOH, JH KAWAS, CH HAYWARD, GS ENDO, H ADLER, WH TI A MOLECULAR HYBRIDIZATION STUDY FOR THE PRESENCE OF HERPES-SIMPLEX, CYTOMEGALOVIRUS AND EPSTEIN-BARR-VIRUS IN BRAIN AND BLOOD OF ALZHEIMERS-DISEASE PATIENTS SO ARCHIVES OF GERONTOLOGY AND GERIATRICS LA English DT Article DE ALZHEIMERS DISEASE; VIRUSES; DNA; DEMENTIA ID DNA; PERSPECTIVES; ZIDOVUDINE; ETIOLOGY; GENOMES; SEARCH; AZT AB Among several hypothesis for the development of Alzheimer's disease is a viral hypothesis. The present study was designed to detect nucleic acid sequences for conventional viruses in peripheral blood cells and brain of Alzheimer's disease patients. DNA was isolated from peripheral blood cells and brain tissue from control individuals and Alzheimer's disease patients. Southern blot analysis was performed using radiolabeled probes for various conventional viruses. The results fail to detect the presence of Herpes simplex 1 (HSV-I), Herpes simplex II (HSV-II), Epstein-Barr virus (EBV) and cytomegalo virus (CMV) at a sensitivity level of detecting 1 genome/100 cells. We exclude conventional viruses as a cause of Alzheimer's disease at this level of detection. C1 NIA,GERONTOL RES CTR,IMMUNOL SECT,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL & MOLEC SCI,BALTIMORE,MD 21205. RP KITTUR, SD (reprint author), NIA,GERONTOL RES CTR,MOLEC NEUROBIOL UNIT,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 29 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0167-4943 J9 ARCH GERONTOL GERIAT JI Arch. Gerontol. Geriatr. PD JUL-AUG PY 1992 VL 15 IS 1 BP 35 EP 41 DI 10.1016/0167-4943(92)90038-6 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA JH356 UT WOS:A1992JH35600005 PM 15374379 ER PT J AU CASTELLI, WP AF CASTELLI, WP TI CONCERNING THE POSSIBILITY OF A NUT SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material RP CASTELLI, WP (reprint author), NATL HEART LUNG & BLOOD INST,5 THURBER ST,FRAMINGHAM,MA 01701, USA. NR 6 TC 9 Z9 10 U1 1 U2 6 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 JUL PY 1992 VL 152 IS 7 BP 1371 EP 1372 DI 10.1001/archinte.152.7.1371 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA JD357 UT WOS:A1992JD35700002 PM 1303626 ER PT J AU CLEGHORN, FR BLATTNER, WA AF CLEGHORN, FR BLATTNER, WA TI DOES HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I AND HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 COINFECTION ACCELERATE ACQUIRED-IMMUNODEFICIENCY-SYNDROME - THE JURY IS STILL OUT SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material ID HTLV-I; INFECTION; HIV-1; CARRIERS; LEUKEMIA; LYMPHOMA; AIDS; STIMULATION; SUPPRESSION; ACTIVATION RP CLEGHORN, FR (reprint author), NCI,DIV CANC ETIOL,VIRAL EPIDEMIOL SECT,6130 EXECUCT BLVD EPN 434,ROCKVILLE,MD 20852, USA. NR 29 TC 22 Z9 22 U1 0 U2 0 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 JUL PY 1992 VL 152 IS 7 BP 1372 EP 1373 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA JD357 UT WOS:A1992JD35700003 PM 1352674 ER PT J AU DREWSBANKIEWICZ, MA CARUSO, RC DATILES, MB KAISERKUPFER, MI AF DREWSBANKIEWICZ, MA CARUSO, RC DATILES, MB KAISERKUPFER, MI TI CONTRAST SENSITIVITY IN PATIENTS WITH NUCLEAR CATARACTS SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID VISUAL-ACUITY; INTERFERENCE-FRINGES; VISION; CHARTS; CAMERA AB Spatial contrast sensitivity and lens density were measured in 30 subjects (18 patients with pure nuclear cataracts and 12 age-matched controls). Contrast sensitivity was assessed using two techniques: a conventional monitor method in which gratings were viewed through the cataract (overall spatial contrast sensitivity) and a laser interferometer method in which gratings were formed directly on the retina (Interferometric spatial contrast sensitivity), thus reducing the effect of an opaque lens on grating contrast. The degree of lens nuclear opacity was measured by assessing the density of Zeiss Scheimpflug slit-lamp video camera images. A contrast sensitivity loss was found by using both methods; this reduction reached statistical significance only when monitor stimuli were used. There was a significant correlation between lens nuclear density and sensitivity loss at spatial frequencies from 4 to 16 cycles/degree (r=.56 to .79 and P<.05 to <.001). A correlation coefficient of .82 (P<.001) characterized the relationship between visual acuity (log of the minimal angle of resolution) and lens density. Nuclear lens opacity significantly affects contrast sensitivity; pure nuclear cataracts produce spatial visual losses at intermediate and high spatial frequencies. RP DREWSBANKIEWICZ, MA (reprint author), NEI,OPHTHALM GENET & CLIN SERV BRANCH,BLDG 10,RM 10N226,BETHESDA,MD 20892, USA. OI Datiles, Manuel III B./0000-0003-4660-1664 NR 27 TC 19 Z9 20 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUL PY 1992 VL 110 IS 7 BP 953 EP 959 PG 7 WC Ophthalmology SC Ophthalmology GA JD336 UT WOS:A1992JD33600015 PM 1637280 ER PT J AU DIWAN, BA NIMS, RW HENNEMAN, JR WARD, JM LUBET, RA RICE, JM AF DIWAN, BA NIMS, RW HENNEMAN, JR WARD, JM LUBET, RA RICE, JM TI EFFECTS OF THE OXAZOLIDINEDIONE ANTICONVULSANTS TRIMETHADIONE AND DIMETHADIONE AND THE BARBITURATE HOMOLOG 5,5-DIMETHYLBARBITURIC ACID ON N-NITROSODIETHYLAMINE-INITIATED RENAL AND HEPATIC CARCINOGENESIS IN THE F344/NCR RAT SO ARCHIVES OF TOXICOLOGY LA English DT Article DE RENAL TUMOR PROMOTION; LIVER TUMOR PROMOTION; OXAZOLIDINEDIONES; BARBITURATES; CYTOCHROME-P450 INDUCTION ID TUMOR-PROMOTING ACTIVITIES; POSITIVE FOCI; BENZODIAZEPINE TRANQUILIZERS; HEPATOCELLULAR NEOPLASMS; EPOXIDE HYDROLASE; BARBITAL SODIUM; DNA-SYNTHESIS; LIVER; INDUCTION; CYTOCHROME-P-450 AB The oxazolidinedione anticonvulsant trimethadione (3,5,5-trimethyl-2,4-oxazolidinedione, TMO) as well as its major metabolite, dimethadione (5,5-dimethyl-2,4-oxazolidinedione, DMO), and a structural analog from the barbiturate series, 5,5-dimethylbarbituric acid (DMB), were fed to F344/NCr male rats previously given a single initiating injection of N-nitrosodiethylamine (NDEA). The known promoter, phenobarbital (5-ethyl-5-phenylbarbituric acid, PB), was employed in this study as a positive control. At dosage levels equimolar to 500 ppm PB, none of the three compounds promoted development of hepatocellular adenomas or carcinomas, in contrast to PB. The two oxazolidinedione analogs and DMB caused minimal or no induction of cytochrome P450 isozyme 2B1 (CYP2B1)-mediated alkoxyresorufin O-dealkylase activities following short-term (2 weeks) feeding to separate groups of 6-week-old male F344/NCr rats, in contrast to the dramatic induction caused by PB. Promotion of neither thyroid nor renal neoplasia was observed following prolonged feeding of any of the tested compounds, although a significantly higher frequency of premalignant renal cortical tubular lesions (dysplasias) was seen in rats exposed to TMO following NDEA initiation than in those treated with NDEA alone. These studies provide important additional data on structure/liver tumor promoting activity relationships, and yield further evidence that within this group of structurally related anticonvulsants, it is possible to separate anticonvulsant activity from tumor promoting activity in the rat liver. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RP DIWAN, BA (reprint author), PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 45 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-5761 J9 ARCH TOXICOL JI Arch. Toxicol. PD JUL PY 1992 VL 66 IS 6 BP 413 EP 422 DI 10.1007/BF02035132 PG 10 WC Toxicology SC Toxicology GA JF110 UT WOS:A1992JF11000008 PM 1444806 ER PT J AU KATZEL, LI COON, PJ BUSBY, MJ GOTTLIEB, SO KRAUSS, RM GOLDBERG, AP AF KATZEL, LI COON, PJ BUSBY, MJ GOTTLIEB, SO KRAUSS, RM GOLDBERG, AP TI REDUCED HDL2 CHOLESTEROL SUBSPECIES AND ELEVATED POSTHEPARIN HEPATIC LIPASE ACTIVITY IN OLDER MEN WITH ABDOMINAL OBESITY AND ASYMPTOMATIC MYOCARDIAL-ISCHEMIA SO ARTERIOSCLEROSIS AND THROMBOSIS LA English DT Article DE OBESITY; SILENT MYOCARDIAL ISCHEMIA; HIGH DENSITY LIPOPROTEINS; HEPATIC LIPASE ID HIGH-DENSITY-LIPOPROTEIN; CORONARY-ARTERY DISEASE; PRECIPITATION PROCEDURE; CARDIOVASCULAR-DISEASE; SELECTIVE MEASUREMENT; RISK-FACTORS; PLASMA; PREVALENCE; HYPOALPHALIPOPROTEINEMIA; SCINTIGRAPHY AB Silent myocardial ischemia (SI), an asymptomatic manifestation of coronary artery disease (CAD), was identified in 10% of apparently healthy nonsmoking, nondiabetic older (60+/-years, mean+/-SD) men with normal plasma cholesterol levels. We hypothesized that in the absence of other major risk factors for CAD, the men with SI would have reduced plasma levels of high density lipoprotein (HDL) and HDL2 subspecies due to an upper-body fat distribution (waist-to-hip ratio [WHR]), hyperinsulinemia, and abnormal postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities. Compared with 47 normal control subjects of similar age, obesity, and maximal aerobic capacity, the 18 men with SI had higher plasma triglyceride (TG) (162+/-71 versus 102+/-39 mg/dl,p<0.001) and lower HDL-C (33+/-6 versus 37+/-7 mg/dl,p<0.02) levels with no difference in low density lipoprotein cholesterol level. The HDL2b and HDL2a subspecies measured by gradient gel electrophoresis were also lower in the men with SI (p<0.01). The plasma glucose and insulin responses during an oral glucose tolerance test were the same in both groups. Postheparin plasma HL activity was significantly higher in 12 men with SI than in 41 control subjects (34+/-8 versus 27+/-10-mu-mol/ml.hr-1, p<0.03) and was correlated with log insulin area (r=0.36, p<0.05) and WHR (r=0.32, p<0.05) in the control subjects but not in the men with SI. In the control group, the percent HDL2b subspecies was correlated inversely with postheparin plasma HL activity (r=-0.46, p<0.01, n=41) as well as WHR (r=-0.49, p<0.001, n=47) and log insulin area (r=-0.37, p<0.05, n=47) but not in the men with SI. Postheparin LPL activity was the same in both groups of men and did not correlate with HDL, WHR, insulin, or plasma TG levels. As the control subjects and men with SI had comparable degrees of abdominal obesity and hyperinsulinemia, these results suggest that the reduced HDL-C levels in men with SI may be related to elevations in HL activity. Thus, abdominal obesity, hyperinsulinemia, elevated TG levels, and low HDL-C and HDL, subspecies levels may predispose these older men to atherosclerosis. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV GERIATR,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DIV CARDIOL,BALTIMORE,MD 21205. FRANCIS SCOTT KEY MED CTR,BALTIMORE,MD. NIA,GERONTOL RES CTR,CLIN PHYSIOL LAB,BALTIMORE,MD 21224. LAWRENCE BERKELEY LAB,BERKELEY,CA 94720. FU NCRR NIH HHS [MO1 RR02719-03]; NIA NIH HHS [P01 AG04402-05, T32 AG00120-02] NR 58 TC 75 Z9 77 U1 1 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1049-8834 J9 ARTERIOSCLER THROMB JI Arterioscler. Thromb. PD JUL PY 1992 VL 12 IS 7 BP 814 EP 823 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JC629 UT WOS:A1992JC62900008 PM 1616906 ER PT J AU SCHAEFER, JR RADER, DJ IKEWAKI, K FAIRWELL, T ZECH, LA KINDT, MR DAVIGNON, J GREGG, RE BREWER, HB AF SCHAEFER, JR RADER, DJ IKEWAKI, K FAIRWELL, T ZECH, LA KINDT, MR DAVIGNON, J GREGG, RE BREWER, HB TI INVIVO METABOLISM OF APOLIPOPROTEIN-A-I IN A PATIENT WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA SO ARTERIOSCLEROSIS AND THROMBOSIS LA English DT Article DE FAMILIAL HYPERCHOLESTEROLEMIA; FRACTIONAL CATABOLIC RATE; APOLIPOPROTEIN-A-I; LOW DENSITY LIPOPROTEINS ID LOW-DENSITY-LIPOPROTEIN; IMMUNOSORBENT-ASSAY ELISA; DEUTERATED LEUCINE; CHOLESTEROL; RECEPTOR; KINETICS; GENE; HYPERLIPOPROTEINEMIA; QUANTITATION; APOPROTEINS AB Familial hypercholesterolemia (FH), caused by a defect in the low density lipoprotein (LDL) receptor, results in high plasma concentrations of LDL cholesterol due to both overproduction and delayed catabolism of LDL. FH is also associated with significantly lower levels of plasma high density lipoprotein cholesterol and apolipoprotein (apo) A-I in both heterozygous and homozygous patients. However, the metabolic basis of the hypoalphalipoproteinemia in FH has not been elucidated. We investigated the kinetics of apo A-I in a homozygous FH patient and two normal control subjects by using endogenous labeling with a stable isotopically labeled amino acid. Study subjects were administered a primed constant infusion of C-13(6)-phenylalanine for 12 hours. Apolipoproteins were isolated from plasma drawn at selected time points and analyzed for their isotopic enrichment by gas chromatography-mass spectrometry. The fractional catabolic rate of apo A-1 in the FH subject was found to be substantially increased (0.38 day-1) compared with that of the normal subjects (mean, 0.26 day-1). In addition, the apo A-I production rate was decreased in the FH subject (6.5 mg/kg.day-1) compared with the normal subjects (mean, 11.1 mg/kg.day-1). In conclusion, the low levels of high density lipoprotein cholesterol and apo A-I in this homozygous FH patient are due to the combined metabolic defects of increased apo A-I catabolism and decreased apo A-I production. C1 CLIN RES INST MONTREAL,MONTREAL H2W 1R7,QUEBEC,CANADA. RP SCHAEFER, JR (reprint author), NHLBI,MOLEC DIS BRANCH,BLDG 10,ROOM 7N117,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 48 TC 47 Z9 48 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1049-8834 J9 ARTERIOSCLER THROMB JI Arterioscler. Thromb. PD JUL PY 1992 VL 12 IS 7 BP 843 EP 848 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JC629 UT WOS:A1992JC62900012 PM 1616910 ER PT J AU TARGOFF, IN TRIEU, EP PLOTZ, PH MILLER, FW AF TARGOFF, IN TRIEU, EP PLOTZ, PH MILLER, FW TI ANTIBODIES TO GLYCYL-TRANSFER RNA-SYNTHETASE IN PATIENTS WITH MYOSITIS AND INTERSTITIAL LUNG-DISEASE SO ARTHRITIS AND RHEUMATISM LA English DT Article ID ANTI-JO-1 ANTIBODY; POLYMYOSITIS DERMATOMYOSITIS; PULMONARY FIBROSIS; AUTOANTIBODIES; JO-1; MARKER; AUTOIMMUNITY; ASSOCIATION; ANTIGEN; SERA AB Objective. We have previously described anti-EJ antibodies, and provided evidence that these antibodies react with glycyl-transfer RNA (gly-tRNA) synthetase. The aim of the present study was to identify patients with anti-EJ antibodies and describe the clinical associations of the antibody, in particular, whether it is associated with the syndrome of myositis and interstitial lung disease (ILD) that has been previously associated with autoantibodies to the aminoacyl-tRNA synthetases for histidine, threonine, and alanine. Methods. Sera from patients with suspected or proven polymyositis or dermatomyositis (DM), sera with anticytoplasmic patterns, and control sera were tested for anti-EJ antibodies by immunoprecipitation (IPP). Positive sera and controls were tested for the ability to inhibit gly-tRNA synthetase by preincubation of the enzyme source with the serum. Results. Anti-EJ antibodies were demonstrated in the sera of 5 patients, by IPP of characteristic tRNAs and protein. Original serum EJ and each of the new sera significantly inhibited the enzymatic activity of gly-tRNA synthetase but not histidyl-tRNA synthetase. All 5 of the new patients had inflammatory myopathy, a typical DM rash, and ILD. One, who had an overlap syndrome with systemic lupus erythematosus, had anti-EJ at least 4 months before the development of clinical myositis. Arthritis and Raynaud's phenomenon, other features associated with antisynthetases, were also seen. Conclusion. Anti-EJ is associated with the syndrome of myositis and lung disease that is seen in association with other antisynthetases. The finding of specific inhibition of gly-tRNA synthetase by all anti-EJ-positive sera strongly supports the identification of EJ antigen as gly-tRNA synthetase. C1 UNIV OKLAHOMA,HLTH SCI CTR,DEPT MED,OKLAHOMA CITY,OK 73190. VET AFFAIRS MED CTR,OKLAHOMA CITY,OK. NIAMSD,BETHESDA,MD. RP TARGOFF, IN (reprint author), OKLAHOMA MED RES FDN,ARTHRIT IMMUNOL SECT,825 NE 13TH ST,OKLAHOMA CITY,OK 73104, USA. OI Miller, Frederick/0000-0003-2831-9593 FU NIAID NIH HHS [AI-21568, AI-27181]; NIAMS NIH HHS [AR-32214] NR 36 TC 71 Z9 71 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUL PY 1992 VL 35 IS 7 BP 821 EP 830 DI 10.1002/art.1780350718 PG 10 WC Rheumatology SC Rheumatology GA JC545 UT WOS:A1992JC54500017 PM 1622421 ER PT J AU LOCKSHIN, MD AF LOCKSHIN, MD TI ENTRY CRITERIA INFLUENCE CONCLUSIONS ABOUT RATES OF FLARE IN LUPUS PREGNANCY - COMMENT SO ARTHRITIS AND RHEUMATISM LA English DT Letter RP LOCKSHIN, MD (reprint author), NIH,BETHESDA,MD 20892, USA. NR 3 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUL PY 1992 VL 35 IS 7 BP 846 EP 846 DI 10.1002/art.1780350734 PG 1 WC Rheumatology SC Rheumatology GA JC545 UT WOS:A1992JC54500033 PM 1622430 ER PT J AU RUSCETTI, FW DUBOIS, CM JACOBSEN, SEW KELLER, JR AF RUSCETTI, FW DUBOIS, CM JACOBSEN, SEW KELLER, JR TI TRANSFORMING GROWTH-FACTOR-BETA AND INTERLEUKIN-1 - A PARADIGM FOR OPPOSING REGULATION OF HEMATOPOIESIS SO BAILLIERES CLINICAL HAEMATOLOGY LA English DT Review ID COLONY-STIMULATING FACTOR; HEMATOPOIETIC STEM-CELLS; HUMAN MARROW CULTURES; NECROSIS FACTOR-ALPHA; RECEPTOR ANTAGONIST PROTEIN; ACUTE MYELOBLASTIC-LEUKEMIA; BONE-MARROW; FORMING CELLS; TGF-BETA; CYTOKINE PRODUCTION C1 FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21701. FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYN CORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21701. FU NCI NIH HHS [N01-CO-74102] NR 91 TC 27 Z9 27 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0950-3536 J9 BAILLIERE CLIN HAEM JI Baillieres Clin. Haematol. PD JUL PY 1992 VL 5 IS 3 BP 703 EP 721 DI 10.1016/S0950-3536(11)80013-2 PG 19 WC Hematology SC Hematology GA JQ853 UT WOS:A1992JQ85300011 PM 1333850 ER PT J AU MCQUILLAN, DJ MIDURA, RJ HASCALL, VC YANAGISHITA, M AF MCQUILLAN, DJ MIDURA, RJ HASCALL, VC YANAGISHITA, M TI PLASMA-MEMBRANE-INTERCALATED HEPARAN-SULFATE PROTEOGLYCANS IN AN OSTEOGENIC CELL-LINE (UMR 106-01 BSP) SO BIOCHEMICAL JOURNAL LA English DT Article ID MAMMARY EPITHELIAL-CELLS; OVARIAN GRANULOSA-CELLS; SULFATE PROTEOGLYCANS; GLYCOSYL-PHOSPHATIDYLINOSITOL; PROTEOHEPARAN SULFATE; PARATHYROID-HORMONE; GROWTH-FACTOR; CORE PROTEIN; SURFACE; METABOLISM AB The heparan sulphate (HS) proteoglycans associated with the cell layer of a rat osteosarcoma cell line [UMR 106-01 (BSP)] were compared with similar cell-associated proteoglycans from other cells, and their interaction with the plasma membrane was studied. HS proteoglycans were metabolically labelled by incubation of cell cultures with [H-3]glucosamine or [H-3]leucine and [S-35]sulphate. HS proteoglycan core protein preparation generated by heparitinase digestion of the major species from UMR 106-01 (BSP) cells co-migrated on PAGE with identical preparations from ovarian granulosa cells and parathyroid cells (at approximately 70 kDa). The hydrophobic nature of the major HS proteoglycans from these diverse cell lines, based on elution position from octyl-Sepharose, were also comparable. Linkages of the HS proteoglycan to the cell membrane were investigated by labelling plasma-membrane preparations with a lipid soluble photoactivatable reagent, 3-(trifluoromethyl)-3-(m-[I-125]iodophenyl)diazirine (TID), which selectively labels plasma-membrane-spanning peptide domains. Purified HS proteoglycan from UMR 106-01 (BSP) cells was shown to be accessible to the [I-125]TID, and the core protein portion of the molecule was labelled, confirming its close association with the plasma membrane. Approx. 36 % of S-35-labelled HS proteoglycans were released from the cell surface by phospholipase C (Bacillus thuringiensis), which specifically cleaves phosphatidylinositol-linked proteins. In the presence of insulin, the metabolism of the phospholipase C-sensitive population was unaltered; however, release of the phospholipase C-insensitive population into the medium was increased. These data indicate that a subpopulation of HS proteoglycans are covalently bound to the plasma membrane by a glycosylphosphatidylinositol structure, with the remainder representing those species directly inserted into the plasma membrane via a hydrophobic peptide domain. These observations are similar to those reported for ovarian granulosa cells [Yanagishita & McQuillan (1989) J. Biol. Chem. 264, 17551-17558], and thus may represent a general phenomenon for many cell types. C1 NIDR, BONE RES BRANCH, BETHESDA, MD 20892 USA. RP MCQUILLAN, DJ (reprint author), UNIV MELBOURNE, ROYAL CHILDRENS HOSP, DEPT PAEDIAT, PARKVILLE, VIC 3052, AUSTRALIA. NR 41 TC 15 Z9 15 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 JUL 1 PY 1992 VL 285 BP 25 EP 33 PN 1 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JC924 UT WOS:A1992JC92400006 PM 1637308 ER PT J AU GBENLE, GO DWYER, DM AF GBENLE, GO DWYER, DM TI PURIFICATION AND PROPERTIES OF 3'-NUCLEOTIDASE OF LEISHMANIA-DONOVANI SO BIOCHEMICAL JOURNAL LA English DT Article ID RAT-HEART; PYRAZOLOPYRIMIDINE METABOLISM; TRYPANOSOMA-BRUCEI; CRITHIDIA-LUCILIAE; PLASMA-MEMBRANE; 5'-NUCLEOTIDASE; NUCLEASE; PROMASTIGOTES; ENDORIBONUCLEASE; LOCALIZATION AB A surface membrane 3'-nucleotidase from Leishmania donovani promastigotes has been purified to SDS/PAGE homogeneity. The enzyme has apparent subunit molecular mass of 38 kDa, pl 5.8 and a broad pH optimum, 5.5-7.5. EDTA partially inhibited the enzyme activity, which was fully restored by Co2+; Mg2+, Ca2+ or Mn2+ had no effect on the activity. ZnCl2 or dithiothreitol at 1 mM was inhibitory at pH 7.5, but was without effect at pH 5.5, whereas at both pH values 5 mM of either compound inhibited the enzyme. The substrate-specificity of the purified enzyme is restricted to ribonucleoside 3'-phosphates. 3'-AMP and 3'-IMP are the best substrates, whereas ADP, ATP, 2'-deoxyadenosine 3'-phosphate and 5'-AMP are competitive inhibitors of the enzyme. The enzyme showed low latency in intact-cell preparations. The kinetic properties and the surface membrane localization of the enzyme suggest its implication in the formation of nucleosides from 3'-nucleotides of the parasite's host. C1 NIH,PARASIT DIS LAB,CELL BIOL & IMMUNOL SECT,BETHESDA,MD 20892. RP GBENLE, GO (reprint author), UNIV LAGOS,COLL MED,DEPT BIOCHEM,PMB 12003,LAGOS,NIGERIA. NR 34 TC 19 Z9 19 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 JUL 1 PY 1992 VL 285 BP 41 EP 46 PN 1 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JC924 UT WOS:A1992JC92400008 PM 1322126 ER PT J AU PIPPIN, CG PARKER, TA MCMURRY, TJ BRECHBIEL, MW AF PIPPIN, CG PARKER, TA MCMURRY, TJ BRECHBIEL, MW TI SPECTROPHOTOMETRIC METHOD FOR THE DETERMINATION OF A BIFUNCTIONAL DTPA LIGAND IN DTPA MONOCLONAL-ANTIBODY CONJUGATES SO BIOCONJUGATE CHEMISTRY LA English DT Note ID RADIOIMMUNOTHERAPY; AGENTS; IONS AB A simple spectrophotometric method was developed to quantitate micromolar concentrations of a bifunctional DTPA ligand in DTPA monoclonal antibody (mAb) conjugates. Titration of a brightly colored 1:2 yttrium(III) complex of arsenazo III with the ligand 1B4M-DTPA obeyed Beer's law over the concentration range 0-2.0-mu-M 1B4M-DTPA at 652 nm. From a calibration plot of absorbance versus 1B4M molarity, concentrations of 1B4M-DTPA conjugated to mAb were determined. Mole ratios of 1B4M-DTPA to mAb agreed satisfactorily with the ratios obtained by a radioanalytical technique using carbon-14-labeled 1B4M-DTPA and a binding assay using In-111. The spectrophotometric method was applied successfully to the preparation of 1B4M-DTPA mAb anti-TAC, a mAb conjugate used in clinical trials of Y-90 radioimmunotherapy. RP PIPPIN, CG (reprint author), NCI,CHEM SECT,RADIAT ONCOL BRANCH,BLDG 10,ROOM B3-B69,BETHESDA,MD 20892, USA. FU NIGMS NIH HHS [5T34-GM-08253] NR 17 TC 112 Z9 114 U1 1 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JUL-AUG PY 1992 VL 3 IS 4 BP 342 EP 345 DI 10.1021/bc00016a014 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA JG232 UT WOS:A1992JG23200014 PM 1390990 ER PT J AU IZARD, ME BONIFACE, GR HARDIMAN, KL BRECHBIEL, MW GANSOW, OA WALKERS, KZ AF IZARD, ME BONIFACE, GR HARDIMAN, KL BRECHBIEL, MW GANSOW, OA WALKERS, KZ TI AN IMPROVED METHOD FOR LABELING MONOCLONAL-ANTIBODIES WITH SM-153 - USE OF THE BIFUNCTIONAL CHELATE 2-(PARA-ISOTHIOCYANATOBENZYL)-6-METHYLDIETHYLENETRIAMINEPENTAACETIC ACID SO BIOCONJUGATE CHEMISTRY LA English DT Note ID AGENTS; RADIOIMMUNOTHERAPY; ANTIGEN; TUMOR; YTTRIUM(III); SM-153; CELLS; LIVER; DTPA AB Samarium-153 (Sm-153) radioimmunoconjugates of the monoclonal antibody K-1-21 were produced using the bifunctional chelate 2-(p-isothiocyanatobenzyl)-6-methyldiethylenetriaminepentaacetic acid (Mx-DTPA). The specific activity (up to 150 MBq mg-1) and percent retained immunoreactivity (>75%) were similar to that of Sm-153-K-1-21 conjugates formed with cyclic DTPA anhydride (cDTPAa). In vivo biodistribution studies showed specific localization of Sm-153-Mx-DTPA-K-1-21 to target antigen implants and higher blood pool and lower uptake in liver, spleen, kidney, and bone when compared to Sm-153-cDTPAa-K-1-21. The improved in vivo distribution of Sm-153-Mx-DTPA-K-1-21 should result in lower radiotoxicity to nontarget tissues when used for radioimmunotherapy purposes. C1 ANSTO, BIOMED & HLTH PROGRAM, SUTHERLAND, NSW, AUSTRALIA. CENTENARY INST CANC MED & CELL BIOL, SYDNEY, NSW, AUSTRALIA. NCI, CHEM SECT, BETHESDA, MD 20892 USA. NR 18 TC 17 Z9 17 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JUL-AUG PY 1992 VL 3 IS 4 BP 346 EP 350 DI 10.1021/bc00016a015 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA JG232 UT WOS:A1992JG23200015 PM 1390991 ER PT J AU KNOBLICH, G CURTIS, D FAUSTMAN, WO ZARCONE, V STEWART, S MEFFORD, I KING, R AF KNOBLICH, G CURTIS, D FAUSTMAN, WO ZARCONE, V STEWART, S MEFFORD, I KING, R TI INCREASED CSF HVA WITH CRAVING IN LONG-TERM ABSTINENT COCAINE ABUSERS SO BIOLOGICAL PSYCHIATRY LA English DT Note ID NUCLEUS-ACCUMBENS; DOPAMINE; ADDICTION; RECEPTORS C1 STANFORD UNIV,DEPT PSYCHIAT & BEHAV SCI,STANFORD,CA 94305. PALO ALTO DEPT VET AFFAIRS MED CTR,PALO ALTO,CA. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. FU NIDA NIH HHS [DA 04789]; NIMH NIH HHS [MH 30854] NR 27 TC 13 Z9 13 U1 2 U2 2 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 JUL 1 PY 1992 VL 32 IS 1 BP 96 EP 100 DI 10.1016/0006-3223(92)90146-Q PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA JR330 UT WOS:A1992JR33000010 PM 1391298 ER PT J AU LAWLOR, BA HILL, JL RADCLIFFE, JL MINICHIELLO, M MOLCHAN, SE SUNDERLAND, T AF LAWLOR, BA HILL, JL RADCLIFFE, JL MINICHIELLO, M MOLCHAN, SE SUNDERLAND, T TI A SINGLE ORAL DOSE CHALLENGE OF BUSPIRONE DOES NOT AFFECT MEMORY PROCESSES IN OLDER VOLUNTEERS SO BIOLOGICAL PSYCHIATRY LA English DT Note ID LORAZEPAM; PERFORMANCE; ALPRAZOLAM; DIAZEPAM; EFFICACY C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RP LAWLOR, BA (reprint author), UNIV DUBLIN,ST JAMES HOSP,PSYCHIAT OLD AGE SECT,DUBLIN 8,IRELAND. NR 11 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 JUL 1 PY 1992 VL 32 IS 1 BP 101 EP 103 DI 10.1016/0006-3223(92)90147-R PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA JR330 UT WOS:A1992JR33000011 PM 1391290 ER PT J AU VENABLE, RM WIDMALM, G BROOKS, BR EGAN, W PASTOR, RW AF VENABLE, RM WIDMALM, G BROOKS, BR EGAN, W PASTOR, RW TI CONFORMATIONAL STATES OF A TT MISMATCH FROM MOLECULAR-DYNAMICS SIMULATION OF DUPLEX D(CGCGATTCGCG) SO BIOPOLYMERS LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; BASE MISMATCHES; LONG-RANGE; DNA; THERMODYNAMICS; MINIMIZATION; ENERGY; HELIX; PAIRS AB The TT mismatch region in duplex d (CGCGATTCGCG) was studied using a 500-ps molecular dynamics (MD) simulation in water, and a series of 1-ps MD simulations and energy minimizations in vacuum. The DNA maintained its duplex structure, although the mismatch region showed significantly higher flexibility than the GC regions. The predominant conformation in the 500-ps MD simulation involved an average -42-degrees propeller twist between T6 and T'6 and a -22-degrees buckle between A5 and T'7. One hydrogen bond was formed between T6 and T'6 and another between T6 and the O2 of T'7, with both Watson-Crick hydrogen bonds between A5 and T'7 remaining intact. The minimizations resulted in conformations with the equivalent hydrogen-bonding pattern, as well as ones with "wobble pair" hydrogen bonds between T6 and T'6. However, the wobble pair conformation was found to be unstable in the water simulation. C1 NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP VENABLE, RM (reprint author), US FDA,CTR BIOL EVALUAT & RES,BIOPHYS LAB,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 36 TC 8 Z9 8 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD JUL PY 1992 VL 32 IS 7 BP 783 EP 794 DI 10.1002/bip.360320707 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA HZ941 UT WOS:A1992HZ94100006 PM 1391631 ER PT J AU CHIARELLI, P BASSER, PJ DEROSSI, D GOLDSTEIN, S AF CHIARELLI, P BASSER, PJ DEROSSI, D GOLDSTEIN, S TI THE DYNAMICS OF A HYDROGEL STRIP SO BIORHEOLOGY LA English DT Article DE CONTINUUM MODEL; POROELASTICITY; VISCOELASTICITY; MATERIAL PROPERTIES; HYDROGEL; ESTIMATION ID ARTICULAR-CARTILAGE; MODEL AB A hydrogel strip relaxes when it is stretched. The decay in tensile stress can be ascribed primarily to strain-induced swelling of the polymer network-a result that follows from a continuum model of the gel-solvent system. An equation of motion and a linear constitutive law of the polymer network, Darcy's law, and the conservation of mass of the network and interstitial fluid are solved with boundary and initial conditions appropriate for a stress-relaxation experiment. This model predicts that the time constant of decay depends inversely upon the square of the thickness of the sample. This result is confirmed by experiments. In addition, the network shear modulus, mu, bulk modulus, k, and hydraulic permeability, 1/f, which are estimated by non-linear regression, all agree with measurements obtained using other methods. C1 NIH,BEIP,BETHESDA,MD 20892. RP CHIARELLI, P (reprint author), UNIV PISA,CTR E PAGGIO,I-56100 PISA,ITALY. RI Basser, Peter/H-5477-2011 NR 24 TC 33 Z9 33 U1 2 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-355X J9 BIORHEOLOGY JI Biorheology PD JUL-AUG PY 1992 VL 29 IS 4 BP 383 EP 398 PG 16 WC Biophysics; Engineering, Biomedical; Hematology SC Biophysics; Engineering; Hematology GA KE830 UT WOS:A1992KE83000001 PM 1306365 ER PT J AU SLIGHTOM, JL SIEU, LC AF SLIGHTOM, JL SIEU, LC TI DIRECT SEQUENCING OF BACULOVIRUS GENOMIC DNA - SEQUENCE DETERMINATION OF THE ENGINEERED RESPIRATORY SYNCYTIAL VIRUS CHIMERIC FG GENE SO BIOTECHNIQUES LA English DT Article ID NUCLEOTIDE-SEQUENCE; GLYCOPROTEIN; CLONING; VECTORS; LIBRARY; SYSTEM; PAIRS; GELS AB Primer-directed enzymatic sequencing has proven to be an efficient and effective method for sequencing various size double-stranded DNA templates. We previously developed a primer-directed sequencing procedure for using double-stranded cosmid (50 kb) DNAs as template. We are interested in using this method to directly sequence larger DNA templates. Towards this goal we applied this method to directly sequence an engineered gene that had been transferred and integrated into the 130-kb baculovirus genome. Both crudely prepared and CsCl gradient-banded baculovirus DNAs were tested and reasonable sequencing ladders were obtained for both types of DNA templates. As little as 3-mu-g of gradient-banded baculovirus DNA were found to be sufficient to obtain film exposure times similar to those observed for cosmid size templates, 24 to 48 h. Effectiveness of the described method was demonstrated by obtaining the complete sequence of the engineered respiratory syncytial virus chimeric FG gene (2.5 kb in length) directly from the recombinant baculovirus "Baculo-FG" genome. Thus, our results demonstrate first, that double-stranded DNA templates as large as 130 kb can be sequenced directly and second, that the nucleotide sequence of engineered genes integrated within the baculovirus genome can be determined without the use of any intermediate steps or procedures. C1 NIH,CTR HUMAN GENOME,BETHESDA,MD 20892. RP SLIGHTOM, JL (reprint author), UPJOHN CO,MOLEC BIOL UNIT 7242,KALAMAZOO,MI 49007, USA. NR 23 TC 7 Z9 7 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 JUL PY 1992 VL 13 IS 1 BP 94 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JC227 UT WOS:A1992JC22700021 PM 1503779 ER PT J AU DYKSTRA, KH WANG, HY AF DYKSTRA, KH WANG, HY TI MONITORING INTRACELLULAR PROTEIN PROFILES WITH 2-DIMENSIONAL GEL-ELECTROPHORESIS SO BIOTECHNOLOGY PROGRESS LA English DT Note ID HIGH-PERFORMANCE ELECTROPHORESIS; TWO-DIMENSIONAL ELECTROPHORESIS; SODIUM DODECYL-SULFATE; CAPILLARY ELECTROPHORESIS; STREPTOMYCES-GRISEUS; POLYACRYLAMIDE GELS; ESCHERICHIA-COLI; URINARY PROTEINS; FERMENTATION; SEPARATION AB Two-dimensional polyacrylamide gel electrophoresis (2D PAGE) is a method of separating complex protein mixtures, such as whole cell extracts, on the basis of protein isoelectric point and molecular weight. In bioprocess engineering, conventional 2D PAGE has tremendous potential to yield detailed information on the intracellular effect of various process conditions. It has been used in our work to examine global intracellular changes occurring in a typical cycloheximide fermentation and to look at the feedback regulatory behavior of cycloheximide biosynthesis. Application of the technique for bioprocess monitoring will require that the time necessary for preparation of a 2D electropherogram be substantially shortened. This may be accomplished by performing the separation on a miniature scale or eventually by use of capillary electrophoresis for one or more of the separations. Advantages and disadvantages of these two approaches are discussed. C1 UNIV MICHIGAN,DEPT CHEM ENGN,ANN ARBOR,MI 48109. RP DYKSTRA, KH (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892, USA. NR 43 TC 3 Z9 3 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD JUL-AUG PY 1992 VL 8 IS 4 BP 369 EP 374 DI 10.1021/bp00016a015 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA JK018 UT WOS:A1992JK01800015 PM 1368457 ER PT J AU SMITH, OM DOLAN, SA DVORAK, JA WELLEMS, TE SIEBER, F AF SMITH, OM DOLAN, SA DVORAK, JA WELLEMS, TE SIEBER, F TI MEROCYANINE-540-SENSITIZED PHOTOINACTIVATION OF HUMAN ERYTHROCYTES PARASITIZED BY PLASMODIUM-FALCIPARUM SO BLOOD LA English DT Note ID CONTINUOUS CULTURE; MEMBRANE; MALARIA; CELLS; PHOTOSENSITIZATION; OXYGEN C1 NIAID,MALARIA RES LAB,BETHESDA,MD 20892. RP SMITH, OM (reprint author), MED COLL WISCONSIN,DEPT PEDIAT,MACC FUND RES CTR,8701 WATERTOWN PLANK RD,MILWAUKEE,WI 53226, USA. FU NCI NIH HHS [CA 42734] NR 23 TC 19 Z9 20 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 1992 VL 80 IS 1 BP 21 EP 24 PG 4 WC Hematology SC Hematology GA JB280 UT WOS:A1992JB28000004 PM 1611086 ER PT J AU HORNUNG, RL LONGO, DL AF HORNUNG, RL LONGO, DL TI HEMATOPOIETIC STEM-CELL DEPLETION BY RESTORATIVE GROWTH-FACTOR REGIMENS DURING REPEATED HIGH-DOSE CYCLOPHOSPHAMIDE THERAPY SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; MICE; INTERLEUKIN-1; RECOVERY C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,FREDERICK,MD 21701. RP HORNUNG, RL (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,POB B,BLDG 567,ROOM 205,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 28 TC 95 Z9 95 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 1992 VL 80 IS 1 BP 77 EP 83 PG 7 WC Hematology SC Hematology GA JB280 UT WOS:A1992JB28000012 PM 1377055 ER PT J AU MACIEJEWSKI, JP BRUENING, EE DONAHUE, RE MOCARSKI, ES YOUNG, NS STJEOR, SC AF MACIEJEWSKI, JP BRUENING, EE DONAHUE, RE MOCARSKI, ES YOUNG, NS STJEOR, SC TI INFECTION OF HEMATOPOIETIC PROGENITOR CELLS BY HUMAN CYTOMEGALOVIRUS SO BLOOD LA English DT Article ID BONE-MARROW-CELLS; VIRUS INFECTION; BLOOD PRODUCTS; TRANSPLANTATION; INVITRO; INTERLEUKIN-1; TRANSMISSION; DEATH C1 UNIV NEVADA,DEPT MICROBIOL,CELL & MOLEC BIOL PROGRAM,RENO,NV 89557. STANFORD UNIV,MED CTR,SCH MED,DEPT MED MICROBIOL,STANFORD,CA 94305. NHLBI,CELL BIOL SECT,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. FU NHLBI NIH HHS [R01HL48503] NR 44 TC 163 Z9 166 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 1992 VL 80 IS 1 BP 170 EP 178 PG 9 WC Hematology SC Hematology GA JB280 UT WOS:A1992JB28000024 PM 1377049 ER PT J AU SHACTER, E ARZADON, GK WILLIAMS, J AF SHACTER, E ARZADON, GK WILLIAMS, J TI ELEVATION OF INTERLEUKIN-6 IN RESPONSE TO A CHRONIC INFLAMMATORY STIMULUS IN MICE - INHIBITION BY INDOMETHACIN SO BLOOD LA English DT Article ID STIMULATORY FACTOR-II; HYBRIDOMA GROWTH-FACTOR; MYELOMA-CELL-GROWTH; CENTRAL NERVOUS-SYSTEM; B-CELLS; RHEUMATOID-ARTHRITIS; MINERAL-OIL; DNA DAMAGE; SERUM; PLASMACYTOMAS RP SHACTER, E (reprint author), NCI,GENET LAB,BLDG 37,ROOM 2B-03,BETHESDA,MD 20892, USA. NR 70 TC 68 Z9 68 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 1992 VL 80 IS 1 BP 194 EP 202 PG 9 WC Hematology SC Hematology GA JB280 UT WOS:A1992JB28000027 PM 1611085 ER PT J AU HYDE, TM MISELIS, RR AF HYDE, TM MISELIS, RR TI SUBNUCLEAR ORGANIZATION OF THE HUMAN CAUDAL NUCLEUS OF THE SOLITARY TRACT SO BRAIN RESEARCH BULLETIN LA English DT Note DE BRAIN-STEM; NUCLEUS OF THE SOLITARY TRACT; AREA POSTREMA; HUMAN; CYTOARCHITECTURE ID BRAIN-STEM PROJECTIONS; DORSAL VAGAL COMPLEX; HUMAN MEDULLA; CATECHOLAMINERGIC NEURONS; VENTROLATERAL MEDULLA; MOTOR COMPONENTS; VAGUS NERVE; RAT; CAT; CONNECTIONS AB The caudal human nucleus of the solitary tract (NTS) is composed of 10 subnuclei. The commissural subnucleus spans the midline below the obex, merging rostrally into the medial subnucleus. The other subnuclei of the NTS are best seen just above the obex. The ventrolateral subnucleus contains large, darkly staining neurons. The interstitial subnucleus consists of neurons lying in groups intermingled with the fibers of the tract. The lateral subnucleus is small at caudal levels, merging with the interstitial subnucleus more rostrally. The dorsal subnucleus contains large melanotic neurons and encircles the substantia gelatinosus, a round, cell-poor subnucleus. The ventromedial subnucleus curls around the medial and ventral edge of the tract. The intermediate subnucleus, laying ventrolateral to the dorsal motor nucleus of the vagus, also contains melanotic neurons. The subpostremal subnucleus separates the area postrema from the NTS proper. The medial subnucleus is the largest subnucleus in the caudal NTS, containing medium-sized fusiform neurons. Adoption of a uniform cytoarchitectural map of the caudal NTS will permit more accurate comparisons between human and nonhuman studies. C1 UNIV PENN,SCH VET MED,ANAT LABS,DEPT ANIM BIOL,PHILADELPHIA,PA 19104. RP HYDE, TM (reprint author), ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH,2700 ML KING JR BLVD,WASHINGTON,DC 20032, USA. NR 29 TC 12 Z9 12 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD JUL PY 1992 VL 29 IS 1 BP 95 EP 109 DI 10.1016/0361-9230(92)90013-N PG 15 WC Neurosciences SC Neurosciences & Neurology GA JD505 UT WOS:A1992JD50500012 PM 1504855 ER PT J AU KOPSTEIN, A AF KOPSTEIN, A TI DRUG-ABUSE RELATED EMERGENCY ROOM EPISODES IN THE UNITED-STATES SO BRITISH JOURNAL OF ADDICTION LA English DT Article AB Drug-related hospital emergency room cases provide one measure of the morbidity associated with drug abuse. Over time, they indicate if problems associated with particular drugs are increasing or decreasing. These trends may be influenced by a number of factors including increased prevalence of use, increased dosages, increased potency, increased frequency of use, the aging of drug addicts, the use of more dangerous routes of administration, and the combined use of two or more drugs. The primary source of this information in the United States is the Drug Abuse Warning Network (DAWN). This paper will present statistics on the drug-related emergencies reported to the DAWN system for 1989 and 1990. In addition to numbers of drug-related emergencies, this paper includes the population based rates for drug-related emergencies in 1990. RP KOPSTEIN, A (reprint author), NIDA,DIV EPIDEMIOL & PREVENT RES,ROCKWALL 2,5514 SECUR LANE,SUITE 615,ROCKVILLE,MD 20852, USA. NR 2 TC 18 Z9 18 U1 0 U2 0 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0952-0481 J9 BRIT J ADDICT PD JUL PY 1992 VL 87 IS 7 BP 1071 EP 1075 PG 5 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA JD863 UT WOS:A1992JD86300013 PM 1643400 ER PT J AU TAYLOR, PR LAWRENCE, CE AF TAYLOR, PR LAWRENCE, CE TI POLYCHLORINATED-BIPHENYLS - ESTIMATED SERUM HALF-LIVES SO BRITISH JOURNAL OF INDUSTRIAL MEDICINE LA English DT Letter ID WORKERS C1 NEW YORK STATE DEPT HLTH,ALBANY,NY 12201. RP TAYLOR, PR (reprint author), NCI,DEPT HLTH & HUMAN SERV,BETHESDA,MD 20892, USA. NR 5 TC 16 Z9 16 U1 0 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0007-1072 J9 BRIT J IND MED PD JUL PY 1992 VL 49 IS 7 BP 527 EP 528 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA JC842 UT WOS:A1992JC84200016 PM 1637716 ER PT J AU LINDBERG, DAB WEST, RT CORN, M AF LINDBERG, DAB WEST, RT CORN, M TI IAIMS - AN OVERVIEW FROM THE NATIONAL-LIBRARY-OF-MEDICINE SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article C1 NATL LIB MED,DIV EXTRAMURAL PROGRAM,BETHESDA,MD 20894. RP LINDBERG, DAB (reprint author), NATL LIB MED,OFF PROGRAM PLANNING & EVALUAT,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 0 TC 15 Z9 15 U1 0 U2 0 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA STE 300, 6 N MICHIGAN AVE, CHICAGO, IL 60602 SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD JUL PY 1992 VL 80 IS 3 BP 244 EP 246 PG 3 WC Information Science & Library Science SC Information Science & Library Science GA JC567 UT WOS:A1992JC56700005 PM 1326366 ER PT J AU HOWARD, FH AF HOWARD, FH TI BROERING,ARTHUR,J. 1932-1992 - OBITUARY SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Item About an Individual RP HOWARD, FH (reprint author), NATL LIB MED,BETHESDA,MD 20209, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA STE 300, 6 N MICHIGAN AVE, CHICAGO, IL 60602 SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD JUL PY 1992 VL 80 IS 3 BP 321 EP 322 PG 2 WC Information Science & Library Science SC Information Science & Library Science GA JC567 UT WOS:A1992JC56700028 ER PT J AU DAY, GL BLOT, WJ AF DAY, GL BLOT, WJ TI 2ND PRIMARY TUMORS IN PATIENTS WITH ORAL-CANCER SO CANCER LA English DT Article DE 2ND PRIMARY TUMORS; ORAL CANCER; PHARYNGEAL CANCER; RISK ID MULTIPLE PRIMARY CANCERS; SQUAMOUS-CELL CARCINOMA; ALCOHOL; TOBACCO; SMOKING; CAVITY; LARYNX AB Background. Patients with cancer of the oral cavity and pharynx have been described to be particularly susceptible to the development of new cancers. Methods. Using data collected during 1973-1987 by nine population-based cancer registries in the United States, the authors evaluated risks of second primary cancers among 21,371 patients in whom oral and pharyngeal cancers were diagnosed. Results. The rate of development of second tumors was 3.7% per year. The risk of a second primary cancer was 2.8 times greater than expected, with 20-fold excesses of second oral or esophageal cancers and 4-fold to 7-fold increases of respiratory cancers. Increased risks persisted unabated for cancers diagnosed 5 or more years after oral cancer, suggesting that the second cancers were new primary tumors and not misdiagnosed metastases. The increased risks of second primary tumors were found among both men and women and black and white patients; they were most prominent among patients who were 60 years or younger. Conclusions. The exceptionally high rate of cancer recurrence among patients with oral cancer (exceeding that for all other cancers) points to the need for close medical surveillance. Special emphasis should be placed on advising patients to avoid or limit consumption of tobacco and alcohol, the main risk factors for oral and most second cancers. C1 NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,ROOM 431,BETHESDA,MD 20892. NR 19 TC 146 Z9 149 U1 1 U2 4 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 JUL 1 PY 1992 VL 70 IS 1 BP 14 EP 19 DI 10.1002/1097-0142(19920701)70:1<14::AID-CNCR2820700103>3.0.CO;2-S PG 6 WC Oncology SC Oncology GA HZ758 UT WOS:A1992HZ75800002 PM 1606536 ER PT J AU BULBULYAN, M ZAHM, SH ZARIDZE, DG AF BULBULYAN, M ZAHM, SH ZARIDZE, DG TI OCCUPATIONAL-CANCER MORTALITY AMONG URBAN WOMEN IN THE FORMER USSR SO CANCER CAUSES & CONTROL LA English DT Article DE CANCER; EPIDEMIOLOGY; ETIOLOGY; MORTALITY; NEOPLASMS; OCCUPATION; USSR; WOMEN AB Occupational cancer mortality was evaluated among approximately three million female pensioners from urban areas of the former USSR. In 1970, these women experienced 14,918 cancer deaths. Occupational data were obtained from death certificates and the 1970 USSR National Population Census. Thirty-five occupational groups, including nine predominantly professional or office-work groups and 26 groups involving physical labor, were evaluated. The expected mortality rates were based on the urban female population of the USSR in 1970. Data for all cancer sites combined, and cancers of the esophagus, stomach, colon, rectum, lung, breast, cervix, and hematopoietic system are presented. Among all female pensioners, there were significant increases of all cancers combined (rate ratio [RR] = 1.05), and cancers of the breast (RR = 1.3), cervix (RR = 1.3), and the hematopoietic system (RR = 1.2), and a significant deficit of cancer of the esophagus (RR = 0.8). Many well-established associations between cancer and occupation among men were observed among the study group of female pensioners, such as stomach and lung cancer among miners, and hematopoietic malignancies among scientists and physicians. Other associations, to be investigated further, also were observed, such as excess lung cancer among waitresses. The peak employment period for this cohort of women was during World War II and the postwar period, when Soviet women outnumbered men almost two-to-one. Consequently, many of the women held jobs that are typically held by men. Thus, this study provides valuable information on occupational risks to women that may be relevant in other countries where women increasingly are being employed in jobs traditionally held by men. C1 NCI,ENVIRONM EPIDEMIOL BRANCH,OCCUPAT STUDIES SECT,EXECUT PLAZA N,ROOM 418,ROCKVILLE,MD 20892. RI Zahm, Shelia/B-5025-2015 NR 0 TC 31 Z9 31 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUL PY 1992 VL 3 IS 4 BP 299 EP 307 DI 10.1007/BF00146882 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA JC108 UT WOS:A1992JC10800001 PM 1617116 ER PT J AU ZAHM, SH HEINEMAN, EF VAUGHT, JB AF ZAHM, SH HEINEMAN, EF VAUGHT, JB TI SOFT-TISSUE SARCOMA AND TOBACCO USE - DATA FROM A PROSPECTIVE COHORT STUDY OF UNITED-STATES VETERANS SO CANCER CAUSES & CONTROL LA English DT Article DE CHEWING TOBACCO; CIGARETTES; EPIDEMIOLOGY; ETIOLOGY; MORTALITY; NEOPLASMS; SMOKELESS TOBACCO; SNUFF; SOFT TISSUE SARCOMA; UNITED-STATES; VETERANS AB A report of an increased risk of soft tissue sarcoma (STS) among users of smokeless tobacco led us to evaluate this association and the role of other types of tobacco in a prospective cohort mortality-study of United States veterans. A total of 248,046 veterans provided tobacco-use histories on a mail questionnaire in 1954 or 1957. Data on subsequent tobacco use were not collected. By 1980, 119 deaths from STS had occurred among the cohort members. Veterans who had ever chewed tobacco or used snuff had a nonsignificant 40 percent excess of STS (95 percent confidence interval [CI] = 0.8-2.6; 21 deaths) in comparison with veterans who had never used any tobacco products. Risk was limited to former users (relative risk [RR] = 1.5) with no excess seen among current users (RR = 0.9). Frequent former users had higher risk (RR = 1.9) than infrequent users (RR = 1.3). Risk was slightly higher in persons who started using smokeless tobacco at younger ages, but did not increase with duration of use or with late age at cessation of use. Most veterans who used chewing tobacco or snuff also used some other form of tobacco. No STS deaths occurred among the 2,308 veterans who used smokeless tobacco only. An unexpected finding of the study was the significant excess of STS deaths among cigarette smokers (RR = 1.8, CI = 1.1-2.9). Risk was higher among ex-smokers (RR = 2.2) than among current smokers (RR = 1.5) and was not related to number of cigarettes per day, age started smoking, duration, or pack-years. Pipe and cigar smokers also experienced a nonsignificant excess risk (RR = 1.6). The study findings may have been affected by limitations in the histories of tobacco use, the quality of death certificate data on STS, and the small number of STS deaths, particularly among users of smokeless tobacco. RP ZAHM, SH (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,ENVIRONM EPIDEMIOL BRANCH,OCCUPAT STUDIES SECT,EXECUT PLAZA N,ROCKVILLE,MD 20892, USA. NR 0 TC 25 Z9 25 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUL PY 1992 VL 3 IS 4 BP 371 EP 376 DI 10.1007/BF00146891 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA JC108 UT WOS:A1992JC10800010 PM 1617125 ER PT J AU FALK, RT PICKLE, LW FONTHAM, ETH GREENBERG, SD JACOBS, HL CORREA, P FRAUMENI, JF AF FALK, RT PICKLE, LW FONTHAM, ETH GREENBERG, SD JACOBS, HL CORREA, P FRAUMENI, JF TI EPIDEMIOLOGY OF BRONCHIOLOALVEOLAR CARCINOMA SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID LUNG-CANCER RISK; ALVEOLAR CELL-CARCINOMA; PASSIVE SMOKING; CHINESE-WOMEN; OCCUPATION; EMPLOYMENT AB Descriptive features of bronchioloalveolar carcinoma (BAC) are presented using Surveillance, Epidemiology and End Results Program population-based incidence data from 1973 through 1987, along with risk factors from histologically confirmed cases of BAC identified in a hospital-based case-control study conducted in Louisiana between 1979 and 1982. Compared to the rising incidence of lung cancer overall, BAC rates have remained relatively constant, accounting for less than 3% of all lung cancer. BAC incidence rates were higher in males, yet it explained proportionately more of the total lung cancer incidence in females. In the case-control study, 21 of the 33 cases originally ascertained from hospital pathology records were histologically confirmed as BAC. Most cases smoked cigarettes, with a 4-fold risk for ever smoking. Risks tended to increase with smoking intensity (reaching 10-fold for more than 1.5 packs/day) and duration (reaching 5-fold for more than 45 years of smoking). Following 10 or more years of employment, there was a 4-fold risk associated with motor freight occupations, along with nonsignificant excesses among construction workers, petroleum manufacturers, and sugar cane farmers. Cases were more likely than controls to have had emphysema or to have had a close family member with lung cancer. Although based on small numbers, this study suggests that BAC shares many of the epidemiological characteristics of lung adenocarcinoma. C1 BAYLOR COLL MED,DEPT PATHOL,HOUSTON,TX 77030. LOUISIANA STATE UNIV,MED CTR,DEPT PATHOL,NEW ORLEANS,LA 70112. RP FALK, RT (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PL N,ROOM 430C,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CP-91023] NR 44 TC 30 Z9 32 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL-AUG PY 1992 VL 1 IS 5 BP 339 EP 344 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA JH382 UT WOS:A1992JH38200001 PM 1339048 ER PT J AU SINGH, J KELLOFF, G REDDY, BS AF SINGH, J KELLOFF, G REDDY, BS TI EFFECT OF CHEMOPREVENTIVE AGENTS ON INTERMEDIATE BIOMARKERS DURING DIFFERENT STAGES OF AZOXYMETHANE-INDUCED COLON CARCINOGENESIS SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ORNITHINE DECARBOXYLASE ACTIVITY; TYROSINE KINASE-ACTIVITY; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; EPITHELIAL PROLIFERATION; CANCER CHEMOPREVENTION; NEOPLASTIC GROWTH; TUMOR DEVELOPMENT; RAT; INDOMETHACIN; INHIBITION AB Chemoprevention of colon cancer is emerging as an alternative to therapy with a broad potential for reducing cancer incidence in defined high-risk groups and the general population. Besides several chemopretentive agents in use and under investigation, D,L-alpha-difluoromethylornithine (DFMO) and piroxicam have been shown to effectively inhibit colon carcinogenesis in rodents. A variety of proliferation-related parameters have been suggested as potential intermediate markers of cancer risk that could be used to monitor the progress of chemoprevention in clinical trials. We have investigated the effect of chemopreventive agents, DFMO, and piroxicam on mucosal ornithine decarboxylase (ODC) and tyrosine-specific protein kinase (TPK) activities during different stages of azoxymethane (AOM)-induced colonic carcinogenesis in male F344 rats in order to examine the plausibility of using these enzymes as intermediate biochemical markers of colon cancer. Groups of male F344 rats were fed modified AIN-76A diets containing 0 or 150 ppm piroxicam or 4000 ppm DFMO and given s.c. injections of AOM dissolved in normal saline at a dose of 15 mg/kg body weight/week, once weekly, for 4 weeks. Vehicle control groups received s.c. equal volumes of normal saline. Groups of animals were then sacrificed at 0, 4, 16, 24, and 32 weeks after AOM or saline treatment, and their colonic mucosa was analyzed for ODC and TPK activities. AOM treatment significantly increased mucosal ODC as well as TPK activities. AOM-induced ODC and TPK activities were significantly suppressed by dietary DFMO progressively at all stages of colon carcinogenesis. Dietary piroxicam increased AOM-induced colonic mucosal ODC and TPK activities but significantly reduced tumor incidence as well as tumor multiplicity. DFMO exerted a more pronounced inhibitory effect on AOM-induced colon tumor development. These results emphasize the importance of development of agent-specific intermediate biomarkers to be used as effective predictors of colon carcinogenesis. C1 NCI,DIV CANC CONTROL & PREVENT,CHEMOPREVENT BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CN-85095-03, CA17613] NR 46 TC 20 Z9 20 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL-AUG PY 1992 VL 1 IS 5 BP 405 EP 411 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA JH382 UT WOS:A1992JH38200011 PM 1305473 ER PT J AU HAND, PH CALVO, B MILENIC, D YOKOTA, T FINCH, M SNOY, P GARMESTANI, K GANSOW, O SCHLOM, J KASHMIRI, SVS AF HAND, PH CALVO, B MILENIC, D YOKOTA, T FINCH, M SNOY, P GARMESTANI, K GANSOW, O SCHLOM, J KASHMIRI, SVS TI COMPARATIVE BIOLOGICAL PROPERTIES OF A RECOMBINANT CHIMERIC ANTICARCINOMA MAB AND A RECOMBINANT AGLYCOSYLATED VARIANT SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE CHIMERIC ANTI-CARCINOMA MAB; AGLYCOSYLATED MAB; BIOLOGIC PROPERTIES ID MURINE MONOCLONAL-ANTIBODIES; CARCINOEMBRYONIC ANTIGEN; EFFECTOR FUNCTIONS; COLORECTAL-CANCER; FC-RECEPTOR; B72.3; BINDING; CELLS; CARBOHYDRATE; COMPLEMENT AB It has been demonstrated previously that the degree of glycosylation of a molecule may alter its pharmacokinetic properties and, in the case of an antibody, its metabolism and other biological properties. Transfectomas producing aglycosylated chimeric B72.3(gamma-1) pancarcinoma monoclonal antibody (mAb) were developed by introduction of the eukaryotic expression construct pECMgpB72.3 HuG1-agly, into SP2/0 murine myeloma cells producing the chimeric kappa-chain of mAb B72.3. After cell cloning, one subclone with the highest binding to the TAG-72-positive human colon carcinoma was designated mAb aGcB72.3, and its biological and biochemical properties were compared with those of the chimeric B72.3(gamma-1), designated mAb CB72.3. Polyacrylamide gel electrophoresis showed that under non-reducing conditions, the molecular masses of the aGcB72.3 and cB72.3 mAbs were 162 kDa and 166 kDa respectively. The heavy chain of mAb aGcB72.3 had a slightly faster mobility than that of cB72.3, while the mobility of the light chains of the two chimeric mAbs was similar. No difference was observed in the isoelectric points of either chimeric mAb. Liquid competition radioimmunoassays demonstrated that the aGcB72.3 and cB72.3 mAbs have comparable binding properties to TAG-72. These studies demonstrate that aglycosylation of the chimeric IgG1 mAb B72.3 at the C(H)2 domain, as has been shown for other mAbs [Dorai H., Mueller B., Reisfeld R.A., Gillies S.D. (1991) Hybridoma 10:211; Morrison S. L., Oi V. T. (1989) Adv Immunol 44:65], eliminates antibody-dependent cell-mediated cytotoxicity activity, but does not substantially alter affinity or plasma clearance in mice. These studies also demonstrate for the first time (a) no difference in plasma clearance of an aglycosylated and a chimeric mAb in a primate after i.v. inoculation; (b) a difference (P less-than-or-equal-to 0.05) in mice in the more rapid peritoneal clearance of a chimeric mAb versus an aglycosylated chimeric mAb; (c) higher (0.05 less-than-or-equal-to P less-than-or-equal-to 0.1) tumor: liver ratios at 24, 72 and 168 h using In-111-labeled aglycosylated chimeric mAb versus chimeric mAb. Since the liver is the major site of metastatic spread for most carcinomas, slight differences in tumor to normal liver ratios may be important in diagnostic applications. These studies thus indicate that comparative analyses of a novel recombinant construct (i.e., aglycosylated) and its standard chimeric counterpart require documentation in more than one system and are necessary if one is ultimately to define optimal recombinant/chimeric constructs for diagnosis and therapy in humans. C1 US FDA,CTR BIOL EVALUAT & RES,DEV PROD QUAL CONTROL,BETHESDA,MD 20892. NCI,RADIAT ONCOL BRANCH,CHEM SECT,BETHESDA,MD 20892. RP HAND, PH (reprint author), NCI,TUMOR IMMUNOL & BIOL LAB,BLDG 10,ROOM 8B07,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 38 TC 26 Z9 26 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD JUL PY 1992 VL 35 IS 3 BP 165 EP 174 DI 10.1007/BF01756183 PG 10 WC Oncology; Immunology SC Oncology; Immunology GA JF450 UT WOS:A1992JF45000003 PM 1638552 ER PT J AU OHSAKI, Y GAZDAR, AF CHEN, HC JOHNSON, BE AF OHSAKI, Y GAZDAR, AF CHEN, HC JOHNSON, BE TI ANTITUMOR-ACTIVITY OF MAGAININ ANALOGS AGAINST HUMAN LUNG-CANCER CELL-LINES SO CANCER RESEARCH LA English DT Article ID ANTIMICROBIAL ACTIVITY; PEPTIDES; SURVIVAL; CARCINOMA; GROWTH; SKIN AB Magainin 1 and magainin 2, originally isolated from African clawed frog Xenopus laevis skin, inhibit the growth of bacteria and fungi. Synthetic magainin A (MAG A) and magainin G (MAG G) are more potent against bacteria and protozoa. In order to determine the antitumor activity of these analogues, we have tested these two analogues against six small cell lung cancer (SCLC) cell lines NCI-H82, NCI-H526, NCI-H678, NCI-H735, NCI-H841, and NCI-H889, which were known to differ by more than 10-fold in their sensitivity to different chemotherapeutic agents, and four normal human fibroblast cell lines. Semiautomated 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays of the six SCLC cell lines revealed average concentrations producing 50% inhibition (IC50) values of 2.6-mu-M (range, 0.49-9.30-mu-M) for cisplatin, 2.5-mu-M (range, 0.39-6.00-mu-M) for etoposide, and 138.8 nM (range, 55.0-450.0 nM) for doxorubicin. The average IC50 of MAG A was 8.64-mu-M (range, 6.23-11.7-mu-M) and that of MAG G was 8.82-mu-M (range, 4.44-12.5-mu-M) against the SCLC cell lines. Despite a 10-fold difference in sensitivity to standard chemotherapeutic agents, the IC50 of MAG A and MAG G differs by <3-fold. The average IC50 against four normal human fibroblast cell lines was 21.1-mu-M (range, 12.7-25.6-mu-M) for MAG A and 29.2-mu-M (range, 21.3-34.8-mu-M) for MAG G. Combined exposure to the IC50 concentration of MAG A or MAG G plus IC50 of etoposide or cisplatin decreased the percentage of surviving SCLC cells to 29.0% (range, 26.1-31.7%). MAG A or MAG G had an additive effect when used with standard chemotherapeutic agents. These data suggest that MAG A and MAG G have in vitro antitumor activity against SCLC cell lines. C1 NCI,NATL NAVAL MED CTR,USN,MED ONCOL BRANCH,BLDG 8,RM 5101,BETHESDA,MD 20889. NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. NR 22 TC 121 Z9 128 U1 0 U2 10 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 JUL 1 PY 1992 VL 52 IS 13 BP 3534 EP 3538 PG 5 WC Oncology SC Oncology GA JA764 UT WOS:A1992JA76400004 PM 1319823 ER PT J AU PERERA, FP MOTZER, RJ TANG, D REED, E PARKER, R WARBURTON, D ONEILL, P ALBERTINI, R BIGBEE, WL JENSEN, RH SANTELLA, R TSAI, WY SIMONCEREIJIDO, G RANDALL, C BOSL, G AF PERERA, FP MOTZER, RJ TANG, D REED, E PARKER, R WARBURTON, D ONEILL, P ALBERTINI, R BIGBEE, WL JENSEN, RH SANTELLA, R TSAI, WY SIMONCEREIJIDO, G RANDALL, C BOSL, G TI MULTIPLE BIOLOGICAL MARKERS IN GERM-CELL TUMOR PATIENTS TREATED WITH PLATINUM-BASED CHEMOTHERAPY SO CANCER RESEARCH LA English DT Article ID SISTER CHROMATID EXCHANGES; CANCER-PATIENTS; DNA ADDUCTS; RECEIVING CHEMOTHERAPY; HUMAN-LYMPHOCYTES; MUTANT FREQUENCY; CISPLATIN; CIS-DIAMMINEDICHLOROPLATINUM(II); ASSAY; QUANTITATION AB Blood samples from 36 germ cell tumor patients receiving chemotherapy with either cisplatin or carboplatin in combination with other drugs [etoposide or vinblastine, cyclophosphamide, dactinomycin, and bleomycin (VAB-6)] were analyzed for the presence of 7 different biological markers. The biomarkers included platinum-protein adducts, platinum-DNA adducts, sister chromatid exchange (SCE), micronuclei (MN), and somatic gene mutation at the hypoxanthine phosphoribosyl transferase (HPRT) locus and the glycophorin A (GPA) loci (NO and NN). Patients were asked to donate 9 serial blood samples: a pretreatment sample followed by another drawn 12-24 h after each of four cycles of treatment and a final sample provided 3-6 months after the last cycle. Most individuals gave 7-8 samples; 7 individuals donated all 9. Because of limited amounts of cells in some cases, it was not possible to carry out all 7 assays on every sample. Pt-protein adducts, Pt-DNA adducts, and SCE showed a direct and consistent effect of treatment and were very highly correlated. A significant correlation was also seen between both Pt-protein and Pt-DNA adducts and HPRT mutation. All of the post-treatment samples were significantly elevated compared to the baseline sample. These markers also remained elevated 3-6 months after the end of treatment. By contrast, MN, HPRT mutation, and GPA mutation (both NO and NN variants) showed varying patterns of dose response, probably reflective of the differing biology of these markers scored in lymphocytes (MN and HPRT) and erythrocytes (GPA). MN were significantly elevated in the posttreatment samples drawn at cycles 2 and 3. Although induction of HPRT mutation was only of marginal significance, results here are for the mutant frequency determination assay only. In progress is the potentially more informative analysis of the type of mutations by Southern blot and the sequencing of mutations to look for characteristic mutational spectra. The GPA assay showed a significant increase over baseline in samples drawn after cycles 3 and 4 (NO variants) and after cycles 2, 3, and 4 (NN variants). The level of GPA mutation (both NO and NN variants) was clearly elevated even 3-6 months after the last cycle of chemotherapy. Correlations were seen between HPRT and MN as well as between GPA NO and GPA NN variants. Analysis of biomarkers by treatment group does not reveal a consistent pattern or trend across all cycles. However, platinum combined with VAB-6 appears to have a greater effect than platinum plus etoposide on SCE, MN, and HPRT at several time points. This may be explained by a greater combined genotoxicity of VAB-6 compared to etoposide and platinum. There was also marked variation in response between individuals receiving the same chemotherapy dose and sampled at the same time point. C1 NCI,BETHESDA,MD 20892. UNIV VERMONT,COLL MED,VERMONT REG CANC CTR,BURLINGTON,VT 05405. LAWRENCE LIVERMORE NATL LAB,LIVERMORE,CA 94550. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. RP PERERA, FP (reprint author), COLUMBIA UNIV,SCH PUBL HLTH,60 HAVEN AVE,B-1,NEW YORK,NY 10032, USA. FU NCI NIH HHS [CA 13696, CA 47351, CA 48518] NR 38 TC 48 Z9 49 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1992 VL 52 IS 13 BP 3558 EP 3565 PG 8 WC Oncology SC Oncology GA JA764 UT WOS:A1992JA76400008 PM 1319825 ER PT J AU ZAHARKO, D PLOWMAN, J WAUD, W DYKES, D MALSPEIS, L AF ZAHARKO, D PLOWMAN, J WAUD, W DYKES, D MALSPEIS, L TI L-HISTIDINOL - PRECLINICAL THERAPEUTIC STUDIES IN COMBINATION WITH ANTITUMOR AGENTS AND PHARMACOKINETIC STUDIES IN MICE SO CANCER RESEARCH LA English DT Article ID INFUSED L-HISTIDINOL; ANTICANCER DRUGS; PROLIFERATION DEPENDENCE; 5-FLUOROURACIL; SPECIFICITY; CELLS; EFFICACY; SCHEDULE; SYSTEM AB Therapeutic studies were conducted with L-histidinol, in combination with cyclophosphamide, bischloroethylnitrosourea, 5-fluorouracil, phenylalanine mustard, or cis-platinum(II)diammine dichloride, in several transplantable tumors in mice. These tumor types included murine L1210 P388 leukemias, M5076 sarcoma, mammary 16/C adenocarcinoma, human LOX melanoma, and colon HT-29 adenocarcinoma. Therapeutic benefits of adding L-histidinol to a regimen, compared to the regimen alone, were marginal. Pharmacokinetic studies indicated a rapid clearance of L-histidinol following a bolus dose (250 mg/kg i.p.), peak plasma concentration of 200-mu-g/ml (1.4 mM), and beta-phase t1/2 of 12.6 min. Maximum tolerable plasma steady state concentrations with a 24-h infusion (2000 mg/kg/24 h) were no greater than 25-mu-g/ml (0.18 mM). C1 NCI,DIV CANC TREATMENT,PHARMACEUT CHEM LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. SO RES INST,BIRMINGHAM,AL 35205. RP ZAHARKO, D (reprint author), NCI,DIV CANC TREATMENT,PHARMACOL BRANCH,DEV THERAPEUT PROGRAM,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CM-73726, N01-CM-67903] NR 17 TC 4 Z9 4 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 JUL 1 PY 1992 VL 52 IS 13 BP 3604 EP 3609 PG 6 WC Oncology SC Oncology GA JA764 UT WOS:A1992JA76400016 PM 1617631 ER PT J AU NERVI, C POINDEXTER, EC GRIGNANI, F PANDOLFI, PP LOCOCO, F AVVISATI, G PELICCI, PG JETTEN, AM AF NERVI, C POINDEXTER, EC GRIGNANI, F PANDOLFI, PP LOCOCO, F AVVISATI, G PELICCI, PG JETTEN, AM TI CHARACTERIZATION OF THE PML-RAR-ALPHA CHIMERIC PRODUCT OF THE ACUTE PROMYELOCYTIC LEUKEMIA-SPECIFIC T(15,17) TRANSLOCATION SO CANCER RESEARCH LA English DT Article ID RETINOIC ACID RECEPTOR; DIFFERENTIATION; HL-60; IDENTIFICATION; CELLS; LOCALIZATION; PROTEINS; BINDING; GENE AB The acute promyelocytic leukemia 15;17 chromosomal translocation fuses the PML gene to the RAR-alpha locus. The resulting chimeric gene encodes for a putative PML-RAR-alpha fusion protein. PML is a putative transcriptional factor and RAR-alpha is one of the nuclear retinoic acid receptors through which retinoic acid regulates gene expression. In this study, we investigated the retinoid binding and biochemical properties of the PML-RAR-alpha protein by size exclusion high-performance liquid chromatography and immunoblot analysis and compared them with those of normal RAR-alpha. The introduction of the expression vector PSG5/PML-RAR-alpha into COS-1 cells led to high levels of expression of the PML-RAR-alpha fusion protein. This protein was primarily localized in the nucleus and bound retinoids with the same affinity and specificity as the wild type RAR-alpha receptor. The PML-RAR-alpha fusion protein, but not the RAR-alpha, was found in high molecular weight complexes with either itself or other nuclear factors. In the acute promyelocytic leukemia-derived cell line NB4, which contains the t(15;17) chromosomal marker, the PML-RAR-alpha product was also found as a high molecular complex. The interaction of the PML-RAR-alpha with itself or with other nuclear proteins may be important in understanding the role of the PML-RAR-alpha fusion protein in promyelocytic leukemogenesis. C1 NIEHS,CELL BIOL SECT,PULM PATHOBIOL LAB,POB 12233,RES TRIANGLE PK,NC 27709. UNIV PERUGIA,MONTELUCE POLICLIN,IST CLIN MED 1,I-06100 PERUGIA,ITALY. UNIV ROME 1,DIPARTIMENTO BIOPATOL,DIV EMATOL,I-00161 ROME,ITALY. OI Avvisati, Giuseppe/0000-0002-5027-5868; Jetten, Anton/0000-0003-0954-4445; NERVI, Clara/0000-0001-9341-0188 NR 35 TC 77 Z9 77 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 JUL 1 PY 1992 VL 52 IS 13 BP 3687 EP 3692 PG 6 WC Oncology SC Oncology GA JA764 UT WOS:A1992JA76400029 PM 1319828 ER PT J AU LEE, SA KARASZKIEWICZ, JW ANDERSON, WB AF LEE, SA KARASZKIEWICZ, JW ANDERSON, WB TI ELEVATED LEVEL OF NUCLEAR-PROTEIN KINASE-C IN MULTIDRUG-RESISTANT MCF-7 HUMAN BREAST-CARCINOMA CELLS SO CANCER RESEARCH LA English DT Article ID HL-60 LEUKEMIA-CELLS; RAT-LIVER NUCLEI; P-GLYCOPROTEIN; CANCER-CELLS; IMMUNOCHEMICAL CHARACTERIZATION; BUTHIONINE SULFOXIMINE; DRUG-RESISTANT; PHORBOL ESTERS; NIH-3T3 CELLS; TUMOR-CELLS AB Previous studies have demonstrated elevated levels of protein kinase C (PKC) activity in multidrug-resistant human breast carcinoma MCF-7/ADR cells compared to control drug-sensitive MCF-7/WT cells (R. L. Fine, J. Patel, and B. A. Chabner, Proc. Natl. Acad. Sci. USA, 85:582-586, 1988). In our present studies, immunohistochemical localization analysis using a polyclonal PKC antibody recognizing the alpha, beta, and gamma-subtypes of PKC demonstrates that immunoreactivity is enhanced in MCF-7/ADR cells, with pronounced staining noted in the nuclear region. Other studies with purified nuclei isolated from MCF-7/ADR cells also show a marked increase in the intensity of immunostaining for PKC when compared to nuclei prepared from control MCF-7/WT cells. Western blot analysis of proteins extracted from purified nuclear preparations further establishes an increase in PKC enzyme protein associated with the nuclear fraction of MCF-7/ADR cells. Subcellular fractionation studies also indicate that MCF-7/ADR cells have 4-8 times higher nuclear PKC activity compared to that of control MCF-7/WT cells. MCF-7/ADR cells also possess 3-5-fold elevated cytosolic PKC activity, while a <2-fold increase is found in PKC activity associated with the plasma membrane fraction of MCF-7/ADR cells. Examination of these extracts with PKC isotype-specific antisera, as well as by DEAE-cellulose chromatography, reveals that nuclei prepared from MCF-7/ADR cells contain markedly elevated amounts of a slightly altered form of PKC-alpha. These results suggest that elevated levels of a modified form of PKC-alpha at the nucleus may play a role in modulating nuclear events to promote the development of multidrug resistance in MCF-7 cells. C1 NCI,CELLULAR ONCOL LAB,BLDG 36,ROOM 1D22,BETHESDA,MD 20892. NR 43 TC 96 Z9 96 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 JUL 1 PY 1992 VL 52 IS 13 BP 3750 EP 3759 PG 10 WC Oncology SC Oncology GA JA764 UT WOS:A1992JA76400039 PM 1617646 ER PT J AU PURI, RK AGGARWAL, BB AF PURI, RK AGGARWAL, BB TI HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TAT GENE UP-REGULATES INTERLEUKIN-4 RECEPTORS ON A HUMAN B-LYMPHOBLASTOID CELL-LINE SO CANCER RESEARCH LA English DT Article ID NECROSIS FACTOR-ALPHA; PERIPHERAL-BLOOD; KAPOSIS-SARCOMA; EXPRESSION; HIV-1; IL-4; PROTEIN; RESPONSIVENESS; MECHANISMS; LESIONS AB The human immunodeficiency virus type I (HIV-1) regulatory gene, tat III is a powerful trans-activator of gene expression from the viral long terminal repeat and is essential for HIV replication. In addition, tat III protein has been shown to be immunosuppressive as indicated by the inhibition of antigen mediated T-cell proliferation. To further test whether tat III might play a direct role in the immunosuppressive effects of HIV-1 in addition to its role in virus replication, we examined the regulation of interleukin 4 (IL-4) receptors on a human B-lymphoblastoid cell line (Raji) transfected with HIV-1 tat gene (Raji-tat III). We used radioligand receptor binding analysis for cell surface expression and Northern blot analysis for the expression of human IL-4 receptor gene in Raji-tat III cells. Control Raji cells expressed 1383 +/- 361 (SE; n = 3) IL-4 binding sites/cell with a dissociation constant (K(d)) of 144 +/- 27 pm (n = 3). However, Raji-tat III cells expressed about three times higher IL-4 receptors (4000 +/- 633 IL-4 binding sites/cell; P < 0.03 compared to Raji cells) with a similar K(d) of 273 +/- 90 pm (n = 3; P > 0.05 compared to Raji cells). Whereas both Raji and Raji-tat III cells exhibited a single mRNA species (approximately 4 kilobases) of IL-4 receptors by Northern blot analysis, the mRNA level was about 3-fold higher in Raji-tat III cells compared to Raji cells. Cycloheximide inhibited the expression of IL-4 receptors by 50% in about 2 h in both cell types indicating both the half-life of IL-4 receptors and the requirement for protein synthesis for the tat III up-regulation of IL-4 receptors. Since IL-4 under certain circumstances has been shown to be immunosuppressant, our observation that the HIV-1 tat gene up-regulates IL-4 receptors suggests the possibility that the immunosuppressive effects of HIV-1 are mediated at least in part through IL-4 receptors. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT CLIN IMMUNOL & BIOL THERAPY,HOUSTON,TX 77030. RP PURI, RK (reprint author), US FDA,CTR BIOLOG EVALUAT & RES,DIV CYTOKINE BIOL,CELLULAR IMMUNOL LAB,NIH BLDG 29A,ROOM 2B20,BETHESDA,MD 20892, USA. RI Aggarwal, Bharat/G-3388-2013 NR 31 TC 53 Z9 53 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 JUL 1 PY 1992 VL 52 IS 13 BP 3787 EP 3790 PG 4 WC Oncology SC Oncology GA JA764 UT WOS:A1992JA76400044 PM 1617647 ER PT J AU LIJINSKY, W THOMAS, BJ KOVATCH, RM AF LIJINSKY, W THOMAS, BJ KOVATCH, RM TI SYSTEMIC AND LOCAL CARCINOGENESIS BY DIRECTLY ACTING N-NITROSO COMPOUNDS GIVEN TO RATS BY INTRAVESICULAR ADMINISTRATION SO CARCINOGENESIS LA English DT Article ID F344 RATS; BLADDER CANCER; MOUSE SKIN; INDUCTION; NITROSOALKYLUREAS; MUTAGENESIS; TUMORS; GAVAGE AB A number of directly acting carcinogenic N-nitroso compounds were administered to female F344 rats intravesically, to assess their ability to induce tumors locally in the urinary bladder and systemically following absorption through the bladder mucosa. The compounds were alkylnitosoureas and alkylnitrosocarbamates and could be formed by interaction of amides with bacterially produced nitrite in infected bladders. Methylnitrosourethane was very toxic: doses of 1 - 2 mg caused death of some rats. A total dose of 0.15 mmol of ethylnitrosourethane, which was much less toxic, was administered to each rat and almost all developed bladder tumors. Ethylnitrosourea also gave rise to bladder tumors following intravesical treatment, and induced some tumors systemically, whereas methylnitrosourea, 2-methoxyethylnitrosourea and 2-hydroxypropylnitrosourea induced bladder tumors in high incidence and few tumors systemically. Nitrosooxazolidone was quite toxic and induced few bladder tumors. The dialkylnitrosoureas were more stable and some induced more tumors systemically than the monoalkylnitrosoureas. 1,3-Dimethylnitrosourea induced no bladder tumors and 1,3-diethylnitrosourea very few, but both induced tumors systemically that were similar to those induced by gavage treatment of rats. 1-Ethyl-1-nitroso-3-hydroxyethylurea, 1-hydroxyethyl-1-nitroso-3-ethylurea and 1-(2-hydroxypropyl)-1-nitroso-3-(2-chloroethyl)-urea induced bladder tumors in a majority of rats treated intravesically; the first induced many tumors systemically. Most of the bladder tumors were transitional cell papillomas and carcinomas, but there were a few squamous cell tumors, smooth muscle tumors, sarcomas and carcinosarcomas. The effects of intravesical administration of the directly acting alkylating compounds are compared with the effects of similar doses given to rats by gavage. C1 NCI,FREDERICK CANC RES & DEV,ABL,BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 29 TC 11 Z9 11 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 JUL PY 1992 VL 13 IS 7 BP 1101 EP 1105 DI 10.1093/carcin/13.7.1101 PG 5 WC Oncology SC Oncology GA JF049 UT WOS:A1992JF04900006 PM 1638674 ER PT J AU SANFORD, KK PRICE, FM RHIM, JS STAMPFER, MR PARSHAD, R AF SANFORD, KK PRICE, FM RHIM, JS STAMPFER, MR PARSHAD, R TI ROLE OF DNA-REPAIR IN MALIGNANT NEOPLASTIC TRANSFORMATION OF HUMAN MAMMARY EPITHELIAL-CELLS IN CULTURE SO CARCINOGENESIS LA English DT Article ID HUMAN EPIDERMAL-KERATINOCYTES; FLUORESCENT LIGHT; CHROMATID DAMAGE; G2 PHASE; GROWTH; RADIOSENSITIVITY; STAGE AB Epithelial cells derived from normal human mammary tissue were examined for capacity to repair radiation-induced chromatin DNA damage. Repair capacity was estimated by quantifying chromatid aberrations in metaphase cells arrested 0.5-1.5 h after X-irradiation during G2. The parental cells at passage 12 had 19 chromatid breaks and 16 gaps per 100 metaphase cells, representing efficient repair. Of two continuous cell lines, derived after benzo[a]pyrene treatment, A1 maintained the efficient repair phenotype through passage 50, while a subline of Al developed the repair-deficient phenotype characterized by a 3- to 5-fold higher frequency of chromatid breaks or gaps. This line was transformed to tumorigenic cells by HaMSV and SV40 T antigen. The second continuous line B5 and derivatives had 102-165 chromatid breaks and 87-134 gaps per 100 metaphases (deficient repair phenotype). This line was transformed to tumorigenic cells by KiMSV. As reported previously for human epidermal keratinocytes, acquisition of this repair-deficient phenotype appears to be an early requisite step in the malignant neoplastic transformation of human cells in culture. C1 UNIV CALIF BERKELEY,BERKELEY,CA 94720. HOWARD UNIV,COLL MED,DEPT PATHOL,WASHINGTON,DC 20001. RP SANFORD, KK (reprint author), NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA-24844] NR 26 TC 14 Z9 14 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 JUL PY 1992 VL 13 IS 7 BP 1137 EP 1141 DI 10.1093/carcin/13.7.1137 PG 5 WC Oncology SC Oncology GA JF049 UT WOS:A1992JF04900011 PM 1638679 ER PT J AU LIJINSKY, W KOVATCH, RM THOMAS, BJ AF LIJINSKY, W KOVATCH, RM THOMAS, BJ TI THE CARCINOGENIC EFFECT OF METHAPYRILENE COMBINED WITH NITROSODIETHYLAMINE GIVEN TO RATS IN LOW-DOSES SO CARCINOGENESIS LA English DT Note ID ENZYME-ALTERED FOCI; HEPATOCARCINOGEN METHAPYRILENE; ANTIHISTAMINE METHAPYRILENE; LIVER CARCINOGENESIS; NATURAL-HISTORY; F344 RATS; DNA; HYDROCHLORIDE; TOXICITY; TUMORS AB The carcinogenic effects of combinations of methapyrilene hydrochloride (MP), nitrosodiethylamine (NDEA), and phenobarbital (PB) or partial hepatectomy (PH) were examined following sequential treatment of rats. MP is a generally non-genotoxic liver carcinogen of moderate potency, NDEA is a genotoxic liver carcinogen, PB is primarily a liver tumor promoter and PH induces cell proliferation. The dose of each carcinogen was chosen to be below that causing significant liver tumor incidence when given singly. There were 12 protocols involving groups of 28 female rats each. Short treatments with NDEA and MP were followed by 60 weeks of PB promotion or by partial hepatectomy. Each treatment was given separately or in double combination as controls. Several animals of each group were killed at intervals during the experiment for examination of toxic effects and the presence of altered hepatic foci. In only 3 of 12 groups was there a significant incidence of rats with liver neoplasms: the two groups given three treatments: NDEA, MP and PB (86% tumors) or NDEA, MP and PH (33%), and the group receiving NDEA and MP without promotion (46%). The results clearly indicated a co-carcinogenic effect between NDEA and MP. Continuous PB potentiated tumor development, while PH did not. There was no evidence of liver toxicity from any of the treatments, but clear cell foci observed in three groups at weeks 13 and 33 correlated with the later development of liver neoplasms. RP LIJINSKY, W (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101] NR 33 TC 7 Z9 7 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 JUL PY 1992 VL 13 IS 7 BP 1293 EP 1297 DI 10.1093/carcin/13.7.1293 PG 5 WC Oncology SC Oncology GA JF049 UT WOS:A1992JF04900037 PM 1638702 ER PT J AU KROEGERKOEPKE, MB MICHEJDA, CJ SMITH, RH AF KROEGERKOEPKE, MB MICHEJDA, CJ SMITH, RH TI ALKYLATION OF DNA BY 1,3-DIALKYL-3-ACYLTRIAZENES - CORRELATION OF BIOLOGICAL-ACTIVITY WITH CHEMICAL BEHAVIOR SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID CROSS-LINKING; DECOMPOSITION; TRIALKYLTRIAZENES; AGENTS; CHLOROETHYLNITROSOUREAS; 1,3-DIALKYLTRIAZENES; RATS AB The reactions of calf thymus DNA with four 1,3-dialkyl-3-acyltriazenes were studied alone or in the presence of pig liver esterase in pH 7.4 phosphate buffer for varying lengths of time. The best alkylating agent in the absence of esterase was determined to be 1,3-dimethyl-3-carbethoxytriazene (DMC), followed in order by 1-(2-hydroxyethyl)-3-methyl-3-carbethoxytriazene (HMC), 1-(2-hydroxyethyl)-3-methyl-3-acetyltriazene (HMA), and 1-(2-chloroethyl)-3-methyl-3-carbethoxytriazene (CMC). This order is the same as that for the rate of decomposition of the various acyltriazenes in pH 7.5 phosphate buffer. The extent of calf thymus DNA alkylation by CMC was found to be dependent on both the reaction buffer and the ionic strength of the medium. Alkylation by CMC alone in low ionic strength glycine buffer produced large quantities of 7-(2-chloroethyl)guanine and 7-(2-hydroxyethyl)guanine. The products of DNA alkylation observed at neutral pH are consistent with N(2)-N(3) heterolysis of the triazene, resulting in the N(1) alkyldiazonium ion as the sole alkylating species. In the presence of esterase, CMC showed an enhanced rate of product formation. Furthermore, the product distribution shifted dramatically from mainly hydroxyethylation to predominantly methylation. CMC is postulated to undergo initial enzymatic deacylation, leading to two different alkyldiazonium ions which competitively alkylate DNA. HMC, on the other hand, was little affected by the esterase. The enzyme-catalyzed reaction showed a small increase in methylation and a smaller decrease in hydroxyethylation. In agreement with these data, the Michaelis-Menten constants for the esterase-catalyzed reaction revealed that HMC was a poorer substrate for the enzyme than was CMC. RP KROEGERKOEPKE, MB (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC ASPECTS DRUG DESIGN SECT,FREDERICK,MD 21702, USA. FU PHS HHS [N01-74101] NR 22 TC 6 Z9 6 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JUL-AUG PY 1992 VL 5 IS 4 BP 541 EP 547 DI 10.1021/tx00028a013 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA JE609 UT WOS:A1992JE60900014 PM 1391620 ER PT J AU GROGAN, J DEVITO, SC PEARLMAN, RS KORZEKWA, KR AF GROGAN, J DEVITO, SC PEARLMAN, RS KORZEKWA, KR TI MODELING CYANIDE RELEASE FROM NITRILES - PREDICTION OF CYTOCHROME P450 MEDIATED ACUTE NITRILE TOXICITY SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID ALIPHATIC NITRILES; INVIVO; MICE AB A mechanism-based model for prediction of acute nitrile toxicity was developed using octanol-water partition coefficients (log P) and estimated rates of alpha-hydrogen atom abstraction as variables. Relative rates of hydrogen atom abstraction were derived from differences in heats of formation for ground-state and radical geometries and radical ionization potentials. Calculated energies of activation for all potential sites of oxidation for a given nitrile were used to estimate partitioning of metabolites among multiple oxidative pathways. log P and the resulting corrected rate constants for alpha-carbon oxidation were effective variables in an acute toxicity model of structurally diverse nitriles. The pharmacokinetics of substrate disposition is discussed in the context of multiple metabolic pathways. Structure-toxicity relationships are also discussed. C1 US EPA,OFF POLLUT PREVENT & TOX TS779,WASHINGTON,DC 20460. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. UNIV TEXAS,COLL PHARM,AUSTIN,TX 78712. NR 28 TC 33 Z9 36 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JUL-AUG PY 1992 VL 5 IS 4 BP 548 EP 552 DI 10.1021/tx00028a014 PG 5 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA JE609 UT WOS:A1992JE60900015 PM 1391621 ER PT J AU MATSUEDA, R YASUNAGA, T KODAMA, H KONDO, M COSTA, T SHIMOHIGASHI, Y AF MATSUEDA, R YASUNAGA, T KODAMA, H KONDO, M COSTA, T SHIMOHIGASHI, Y TI DESIGN AND SYNTHESIS OF HIGHLY SPECIFIC AND SELECTIVE ENKEPHALIN ANALOG CONTAINING S-NPYS-CYSTEINE FOR DELTA-OPIOID RECEPTORS SO CHEMISTRY LETTERS LA English DT Article ID OPIATE RECEPTORS; INACTIVATION AB Enkephalin analogs containing S-(3-nitro-2-pyridinesulfenyl)cysteine at positions of 1, 5, or 6 were synthesized for searching possible thiol groups in the opioid receptors. In the radio-ligand receptor assay and biological assays, [D-Ala2, Leu5]enkephalyl-Cys(Npys)6 exhibited a very high affinity and selectivity for delta over mu-receptors, and its covalent attachment to delta-receptors through the disulfide bonding was evidenced. C1 KYUSHU UNIV, FAC SCI, DEPT CHEM, BIOCHEM LAB, FUKUOKA 812, JAPAN. SANKYO CO LTD, NEW LEAD RES LABS, TOKYO 140, JAPAN. NICHHD, BETHESDA, MD USA. SAGA UNIV, FAC SCI & ENGN, DEPT CHEM, SAGA 840, JAPAN. NR 8 TC 10 Z9 10 U1 0 U2 0 PU CHEMICAL SOC JAPAN PI TOKYO PA 1-5 KANDA-SURUGADAI CHIYODA-KU, TOKYO, 101-8307, JAPAN SN 0366-7022 EI 1348-0715 J9 CHEM LETT JI Chem. Lett. PD JUL PY 1992 IS 7 BP 1259 EP 1262 DI 10.1246/cl.1992.1259 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA JF174 UT WOS:A1992JF17400041 ER PT J AU KEDDERIS, LB DILIBERTO, JJ JACKSON, JA LINKO, P GOLDSTEIN, JA BIRNBAUM, LS AF KEDDERIS, LB DILIBERTO, JJ JACKSON, JA LINKO, P GOLDSTEIN, JA BIRNBAUM, LS TI EFFECTS OF DOSE AND ROUTE OF EXPOSURE ON DIOXIN DISPOSITION SO CHEMOSPHERE LA English DT Article; Proceedings Paper CT 11TH INTERNATIONAL SYMP ON CHLORINATED DIOXINS AND RELATED COMPOUNDS CY SEP 23-27, 1991 CL RESEARCH TRIANGLE PK, NC ID ETHOXYRESORUFIN O-DEETHYLASE; HEPATIC-UPTAKE; AH RECEPTOR; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; METABOLISM; INDUCTION; AGONISTS; BINDING; RATS AB The absorption, distribution, metabolism and excretion of 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) was studied in male F344 rats. Oral absorption was dose-dependent. Absorption of 1 nmol/kg by both the oral and intratacheal (itr) routes was approximately 80%, whereas only approximately 12% was absorbed through the skin. Tissue distribution was dependent on dose, time, and route of exposure. Liver:fat ratios of 3.4, 2.9, 2.0, and 1.5 were observed 3 days after iv, oral itr, and dermal administration, respectively, of 1 nmol/kg. Liver:fat ratios were 0.2 and 2.6 by 56 days after 1 and 100 nmol/kg iv, respectively. Dose-depend-ent elimination in urine and feces was observed beginning 3 weeks after iv administration. However, auto-induction of dioxin metabolism did not occur in vivo when evaluated by bilary excretion of [H-3]TBDD or [H-3]TCDD in pretreated and naive rats. Dose-response profiles for TBDD induction of hepatic cytochromes CYP1A1 and CYP1A2 indicated the latter to be more sensitive response. Finally, comparison of the dose-response behavior for TBDD induction of hepatic CYP1A2 with hepatic concentrations of TBDD Suggests that induction of CYP1A2 alone does not account for nonlinearities in dioxin disposition exemplified by dose-related increase in the ratio of dioxin concentrations in liver and fat. C1 US EPA,RES TRIANGLE PK,NC 27711. NIEHS,RES TRIANGLE PK,NC 27709. METI,RES TRIANGLE PK,NC. RP KEDDERIS, LB (reprint author), UNIV N CAROLINA,CURRICULUM TOXICOL,CHAPEL HILL,NC 27514, USA. NR 15 TC 2 Z9 2 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD JUL PY 1992 VL 25 IS 1-2 BP 7 EP 10 DI 10.1016/0045-6535(92)90467-6 PG 4 WC Environmental Sciences SC Environmental Sciences & Ecology GA JN851 UT WOS:A1992JN85100002 ER PT J AU LUSTER, MI HOLLADAY, SD BLAYLOCK, BL GERMOLEC, DR CLARK, GC COMMENT, CE HEINDEL, JJ ROSENTHAL, GJ AF LUSTER, MI HOLLADAY, SD BLAYLOCK, BL GERMOLEC, DR CLARK, GC COMMENT, CE HEINDEL, JJ ROSENTHAL, GJ TI TCDD INHIBITS MURINE THYMOCYTE AND B-LYMPHOCYTE MATURATION SO CHEMOSPHERE LA English DT Article; Proceedings Paper CT 11TH INTERNATIONAL SYMP ON CHLORINATED DIOXINS AND RELATED COMPOUNDS CY SEP 23-27, 1991 CL RESEARCH TRIANGLE PK, NC ID 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN AB Immunotoxicity is a common occurrence in experimental animals following exposure to TCDD. In addition to thymic atrophy, immunotoxicity is characterized by suppression of antibody responses in adult mice and suppression of cell-mediated immunity following perinatal exposure. Studies in our laboratory have investigated the effects of prenatal TCDD exposure on thymocyte maturation and differentiation. In addition, we have examined TCDD-induced effects on B lymphocyte maturation and differentiation in vitro. RP LUSTER, MI (reprint author), NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709, USA. NR 6 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 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD JUL PY 1992 VL 25 IS 1-2 BP 115 EP 118 DI 10.1016/0045-6535(92)90493-B PG 4 WC Environmental Sciences SC Environmental Sciences & Ecology GA JN851 UT WOS:A1992JN85100028 ER PT J AU HUFF, J AF HUFF, J TI 2,3,7,8-TCDD - A POTENT AND COMPLETE CARCINOGEN IN EXPERIMENTAL-ANIMALS SO CHEMOSPHERE LA English DT Article; Proceedings Paper CT 11TH INTERNATIONAL SYMP ON CHLORINATED DIOXINS AND RELATED COMPOUNDS CY SEP 23-27, 1991 CL RESEARCH TRIANGLE PK, NC ID 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; TOXICITY; DIOXINS; CANCER; RATS AB Long-term carcinogenesis studies using laboratory animals exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have shown conclusively that this chemical is a complete carcinogen. In a series of independent studies from the first reported in 1977 to the latest in 1988, TCDD has consistently induced cancers in a variety of organs and systems. TCDD-induced neoplastic lesions occurred in each of 18 individual sex-species experiments. In rats, TCDD induced neoplasms in lung, oral/nasal cavities, thyroid and adrenal glands, and liver. In mice, TCDD caused neoplasms in the liver, subcutaneous tissue, thyroid gland, lung, and lympjopoietic system (lymphomas). In hamsters, TCDD produced squamous cell carcinomas of the facial skin. TCDD is a trans-species (rat, mouse, and hamster), trans-strain (Sprague-Dawley and Osborne-Mendel rats; B6C3F1, Swiss-Webster, and B6C mice), trans-sex, multi-site, complete carcinogen. The most potent of the identified chemical carcinogens, TCDD induced carcinogenic effects in laboratory animals with exposures as low as 0.001 ug/kg body weight/day. Proposed mechanism(s) of TCDD-induced carcinogenesis have yet to account for the many relatively rare types of tumors observed in exposed animals. In two-stage liver or skin models, TCDD exhibits considerable tumor promotion activity. With respect to carcinogenic hazards to humans, these experimental data alone indicate that TCDD should be considered for practical and public health purposes as being likely to be carcinogenic to humans; this species extrapolative conclusion gains growing support from epidemiological studies showing clear associations between exposure to dioxin and increases in cancers of the respiratory system (particularly lung), soft-tissue sarcomas, and total cancers. Other risks appear to be elevated for cancers of the testicle, thyroid gland, and other endocrine glands, largely in workers exposed to chlorophenoxy herbicides. Thus, using the collective experimental and epidemiological evidence, the prudent course of action would be to minimize to the greatest extent possible all potential exposures to this and other dioxins as well as to phenoxyacid herbicides, and where technologically and argiculturally feasible exposures should be eliminated. RP HUFF, J (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 30 TC 18 Z9 18 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD JUL PY 1992 VL 25 IS 1-2 BP 173 EP 176 DI 10.1016/0045-6535(92)90506-M PG 4 WC Environmental Sciences SC Environmental Sciences & Ecology GA JN851 UT WOS:A1992JN85100041 ER PT J AU LUCIER, GW CLARK, G TRITSCHER, A FOLEY, J MARONPOT, R AF LUCIER, GW CLARK, G TRITSCHER, A FOLEY, J MARONPOT, R TI MECHANISMS OF DIOXIN TUMOR PROMOTION - IMPLICATIONS FOR RISK ASSESSMENT SO CHEMOSPHERE LA English DT Article; Proceedings Paper CT 11TH INTERNATIONAL SYMP ON CHLORINATED DIOXINS AND RELATED COMPOUNDS CY SEP 23-27, 1991 CL RESEARCH TRIANGLE PK, NC ID 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; HEPATOCARCINOGENESIS; TOXICITY AB TCDD is a liver carcinogen in female rats but not male rats. In a two stage model for hepatocarcinogenesis, using a single initiating dose of diethylnitrosamine (DEN) and chronic exposure to TCDD (25 ng/kg/day for 30 weeks), ovariectomy prevented the tumor promoting actions of TCDD. This finding was consistent with data on cell proliferation which demonstrated that TCDD did not induce cell proliferation in the absence of the ovaries. Dose-response data were obtained for a number of responses to TCDD within the framework of a tumor promotion model. These included cell proliferation, number and size of hepatic preneoplastic foci, induction of cytochrome P-450 isozymes (CYP 1A1 and 1A2), TCDD liver and blood concentrations, epidermal growth factor (EGF) receptor, estrogen receptor, histological changes and clinical chemistries. Dose response relationships were markedly different for the different parameters. For example, CYP 1A1 and 1A2 induction occurred at lower doses than effects of cell proliferation and preneoplastic lesions. The relevance of these data to low dose human risks and rodent to human extrapolations of risks are discussed. RP LUCIER, GW (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 16 TC 5 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD JUL PY 1992 VL 25 IS 1-2 BP 177 EP 180 DI 10.1016/0045-6535(92)90507-N PG 4 WC Environmental Sciences SC Environmental Sciences & Ecology GA JN851 UT WOS:A1992JN85100042 ER PT J AU XU, YH DRAGAN, YP MARONPOT, RR GOLDSWORTHY, TL PITOT, HC AF XU, YH DRAGAN, YP MARONPOT, RR GOLDSWORTHY, TL PITOT, HC TI CRITERIA, MECHANISMS, AND POTENCY EVALUATION FOR TUMOR PROMOTERS - DIOXIN AS A MODEL SO CHEMOSPHERE LA English DT Article; Proceedings Paper CT 11TH INTERNATIONAL SYMP ON CHLORINATED DIOXINS AND RELATED COMPOUNDS CY SEP 23-27, 1991 CL RESEARCH TRIANGLE PK, NC ID ALTERED HEPATIC FOCI; FEMALE RATS; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; HEPATOCARCINOGENESIS; DIETHYLNITROSAMINE AB The promotion stage of cancer development involves the reversible clonal growth of initiated cells with an altered expression of several protein markers. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent promoting agent known with a Promotion Index in excess of 10(6). The time dependence (1-5 months) of promotion by biweekly injections of 0.14-mu-g TCDD/kg (equivalent to 0.01-mu-g TCDD/day) was determined in female rats treated with diethylnitrosamine (10 mg/kg) in an initiation-promotion paradigm. In addition, the reversibility of promotion by TCDD was assessed in rats maintained for 6 months without TCDD administration after 1 to 5 months of TCDD administration. Whereas the number of altered hepatic foci (AHF) observed was decreased in animals promoted with TCDD and subsequently withdrawn from further TCDD administration for 6 months prior to sacrifice, the volume percentage of the liver occupied by AHF was increased with this regimen, suggesting that sufficient TCDD may remain in the liver after 6 months to maintain promotion or, alternatively, that TCDD exhibits progressor as well as promoter activity. C1 NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. CHEM IND INST TOXICOL,RES TRIANGLE PK,NC 27709. RP XU, YH (reprint author), UNIV WISCONSIN,SCH MED,MCARDLE LAB CANC RES,MADISON,WI 53706, USA. NR 9 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 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD JUL PY 1992 VL 25 IS 1-2 BP 227 EP 230 DI 10.1016/0045-6535(92)90520-2 PG 4 WC Environmental Sciences SC Environmental Sciences & Ecology GA JN851 UT WOS:A1992JN85100055 ER PT J AU EDLER, L PORTIER, CJ AF EDLER, L PORTIER, CJ TI UNCERTAINTY IN PHYSIOLOGICAL PHARMACOKINETIC MODELING AND ITS IMPACT ON STATISTICAL RISK-ESTIMATION OF 2,3,7,8 TCDD SO CHEMOSPHERE LA English DT Article; Proceedings Paper CT 11TH INTERNATIONAL SYMP ON CHLORINATED DIOXINS AND RELATED COMPOUNDS CY SEP 23-27, 1991 CL RESEARCH TRIANGLE PK, NC ID 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN AB Uncertainty predictions resulting from Physiologically-based Pharmacokinetic Models (PPM) is discussed for human risk assessment. Approaches to assess statistical uncertainty are developed and applied to the study of dioxin (2,3,7,8 TCDD). RP EDLER, L (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 8 TC 4 Z9 4 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD JUL PY 1992 VL 25 IS 1-2 BP 239 EP 242 DI 10.1016/0045-6535(92)90523-T PG 4 WC Environmental Sciences SC Environmental Sciences & Ecology GA JN851 UT WOS:A1992JN85100058 ER PT J AU QUYYUMI, AA PANZA, JA DIODATI, JG LAKATOS, E EPSTEIN, SE AF QUYYUMI, AA PANZA, JA DIODATI, JG LAKATOS, E EPSTEIN, SE TI CIRCADIAN VARIATION IN ISCHEMIC THRESHOLD - A MECHANISM UNDERLYING THE CIRCADIAN VARIATION IN ISCHEMIC EVENTS SO CIRCULATION LA English DT Article DE CIRCADIAN RHYTHM; ISCHEMIA, MYOCARDIAL; TONE, VASCULAR ID CORONARY-ARTERY DISEASE; SUDDEN CARDIAC DEATH; MORNING INCREASE; ANGINA-PECTORIS; PLATELET AGGREGABILITY; MYOCARDIAL-INFARCTION; DIURNAL-VARIATION; STABLE ANGINA; EXERCISE; FREQUENCY AB Background. There is a circadian pattern in the occurrence of cardiac events in patients with coronary artery disease. Whether changes in coronary vascular tone contribute to these phenomena is unknown. We measured the ischemic threshold, defined as either the heart rate or rate-pressure product at 1-mm ST segment depression during treadmill exercise and used it as an index of the lowest coronary vascular resistance; the premise was that when ischemic threshold became lower, coronary vascular resistance was higher, and vice versa. Methods and Results. Fifteen patients (group A) with stable coronary artery disease underwent four identical treadmill exercise tests in 24 hours, and ischemic threshold was measured as the heart rate at the onset of 1-mm ST depression. Before each treadmill test, postischemic forearm vascular resistance was measured after 5 minutes of forearm occlusion, using strain-gauge plethysmography. Sixteen additional patients (group B) underwent two treadmill tests at 8 AM and 1 PM, and ischemic threshold was measured as the heart rate-blood pressure product at 1-mm ST depression. A circadian variation was noted: In group A, the heart rate-derived ischemic threshold was lower at 8 AM and 9 PM compared With noon and 5 PM (p<0.03). Also, in group B, the rate-pressure product-derived ischemic threshold was 8+/-2% lower at 8 AM compared with 1 PM (p=0.008). A circadian variation parallel to the observed variation in ischemic threshold was also noted in the postischemic forearm blood flow, which was lower in the morning and at night (p<0.004). There was a strong correlation between postischemic forearm blood flow and ischemic threshold (p<0.0001), such that ischemic threshold was lower at the time of day when postischemic forearm blood How was lower, and vice versa. Conclusions. A lower ischemic threshold in the morning suggests that the ischemia-induced coronary vascular resistance is increased at this time, a finding supported by a similar variation in postischemic forearm vascular resistance. Parallel changes in forearm and coronary resistance suggest that generalized (neural or humoral factors) rather than local factors are responsible for the observed circadian changes. Increased coronary tone in the mornings may not only contribute to the higher incidence of transient ischemia but may help trigger acute cardiac events at this time. RP QUYYUMI, AA (reprint author), NHLBI,CARDIOL BRANCH,BLDG 10,ROOM 7B15,BETHESDA,MD 20892, USA. NR 28 TC 93 Z9 93 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL PY 1992 VL 86 IS 1 BP 22 EP 28 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JC457 UT WOS:A1992JC45700003 PM 1617775 ER PT J AU DAVIDSON, CJ BASHORE, TM MICKEL, M DAVIS, K AF DAVIDSON, CJ BASHORE, TM MICKEL, M DAVIS, K TI BALLOON MITRAL COMMISSUROTOMY AFTER PREVIOUS SURGICAL COMMISSUROTOMY SO CIRCULATION LA English DT Article DE STENOSIS, MITRAL; VALVOTOMY, MITRAL; COMMISSUROTOMY, SURGICAL; BALLOON VALVULOPLASTY ID FOLLOW-UP; VALVULOPLASTY; RESTENOSIS; VALVOTOMY; VALVE; MECHANISM; STENOSIS AB Background. Mitral restenosis after surgical mitral commissurotomy often occurs within 5-15 years, necessitating a repeat procedure. Balloon mitral commissurotomy (BMC) has been advocated as an alternative to repeat surgery for mitral restenosis. Methods and Results. The purposes of this study are to determine the short- and intermediate-term outcomes of patients undergoing BMC after previous surgical commissurotomy, to compare these patients with those undergoing balloon mitral commissurotomy as an initial procedure, and to elucidate the multivariate determinants of acute procedural and clinical outcome. Of 738 patients undergoing BMC as part of the National Heart, Lung, and Blood Institute Balloon Valvuloplasty Registry, 133 underwent BMC after previous surgical mitral commissurotomy. Prospective data obtained included demographic, hemodynamic, echocardiographic, and clinical follow-up. BMC after previous surgical commissurotomy produced a significant reduction in transvalvular gradient from 13+/-5 to 6+/-3 mm Hg (p<0.0001) and an increase in mitral valve area from 1.0+/-03 to 1.8+/-0.8 cm2 (p<0.0001). BMC as an initial procedure increased valve area from 1.0+/-0.4 to 2.0+/-0.8 cm2 (p<0.0001) (p=0.03 versus prior surgery). Baseline characteristics including mitral valve echo score were similar for both groups. Comparing 6-month status in patients with prior surgery to those without, 80% versus 90% were New York Heart Association (NYHA) functional class I or II (p=0.004). Mortality was similar. In patients with previous mitral valve surgery, multivariate predictors of improvement in 6-month clinical status included the experience of the center (p=0.006), lower echocardiographic score (p=0.001), and lower left ventricular end-diastolic pressure (p=0.008). Multivariate determinants of a final mitral valve area greater-than-or-equal-to 1.5 cm2 were a lower baseline NYHA functional class (p=0.003) and lower mitral valve echocardiographic score (p=0.008). Conclusions. BMC after previous surgical mitral commissurotomy results in similar hemodynamic changes as in patients undergoing BMC as an initial procedure. Symptomatic improvement at 6 months is slightly less frequent in prior commissurotomy patients. Patients with favorable valvular morphology and preserved left ventricular function who undergo BMC in experienced centers are most likely to achieve symptomatic improvement after previous surgical commissurotomy. In general, BMC is an effective treatment for mitral restenosis after previous surgical commissurotomy. C1 NHLBI,BETHESDA,MD 20892. FU NHLBI NIH HHS [N01-HV-78100] NR 20 TC 35 Z9 37 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL PY 1992 VL 86 IS 1 BP 91 EP 99 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JC457 UT WOS:A1992JC45700011 PM 1617794 ER PT J AU FRASER, DD KONG, LI MILLER, FW AF FRASER, DD KONG, LI MILLER, FW TI MOLECULAR-DETECTION OF PERSISTENT BORRELIA-BURGDORFERI IN A MAN WITH DERMATOMYOSITIS SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article DE LYME DISEASE; DERMATOMYOSITIS; POLYMERASE CHAIN REACTION ID POLYMERASE CHAIN-REACTION; LYME-DISEASE; MYOSITIS; ARTHRITIS; INFECTION; RESPONSES; ASSAY; FLUID; BLOOD AB A 40-year-old white man with a several year history of various immunologic disorders, including anti-Jo-1 autoantibody positive dermatomyositis, developed clinical Lyme disease after being biten by a tick. The patient was treated with oral tetracycline and his initial symptoms resolved; however, he suffered an exacerbation of his muscle disease which was difficult to control despite cytotoxic therapy. Antibiotic therapy was reinstituted after Borrelia burgdorferi was detected in the patient's peripheral blood leukocytes by the polymerase chain reaction (PCR). All serologic, T-cell stimulation, and western blot analyses, however, were negative. The patient's disease responded to oral ampicillin, probenicid therapy and concurrent cytotoxic therapy. Subsequent leukocyte PCR testing has been negative for the causative agent of Lyme disease. This case may provide an example of the in vivo immuno-modulatory effects of spirochetes in human autoimmune disease. In addition, this case emphasizes the potential clinical utility of PCR technology in evaluating the persistant seronegative Lyme disease which may occur in immunocompromised individuals. C1 NIAMSD,8800 ROCKVILLE PIKE,HFB 700,BLDG 29,ROOM 516,BETHESDA,MD 20892. MICROBIOL REFERENCE LAB,CYPRESS,CA. OI Miller, Frederick/0000-0003-2831-9593 NR 26 TC 24 Z9 25 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD JUL-AUG PY 1992 VL 10 IS 4 BP 387 EP 390 PG 4 WC Rheumatology SC Rheumatology GA JF194 UT WOS:A1992JF19400011 PM 1395222 ER PT J AU GRADON, JD TIMPONE, JG SCHNITTMAN, SM AF GRADON, JD TIMPONE, JG SCHNITTMAN, SM TI EMERGENCE OF UNUSUAL OPPORTUNISTIC PATHOGENS IN AIDS - A REVIEW SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNE-DEFICIENCY SYNDROME; HYDROPHILA-ASSOCIATED COLITIS; CYTOMEGALO-VIRUS INFECTION; DISSEMINATED HISTOPLASMOSIS; ACALCULOUS CHOLECYSTITIS; VISCERAL LEISHMANIASIS; EPITHELIOID ANGIOMATOSIS; BACILLARY ANGIOMATOSIS; CAMPYLOBACTER-JEJUNI AB Opportunistic infections are a major cause of morbidity and death among patients infected with the human immunodeficiency virus (HIV), particularly late in the disease, when immunosuppression is severe. Some pathogens, such as Pneumocystis carinii and Toxoplasma gondii, are extremely common in this population and are readily recognized by clinicians caring for these patients. However, many other organisms occasionally cause conditions that clinically mimic the more commonly encountered pathogens. Clinicians must be alert to the threat posed by these less frequently occurring organisms and of the broader differential diagnosis that must be considered for infections in patients with HIV infection. RP GRADON, JD (reprint author), NIAID,DIV AIDS,MED BRANCH,6003 EXECUT BLVD,ROCKVILLE,MD 20892, USA. NR 161 TC 50 Z9 50 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL PY 1992 VL 15 IS 1 BP 134 EP 157 PG 24 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JA300 UT WOS:A1992JA30000020 PM 1617054 ER PT J AU COOPER, MR LIEBERMAN, R LAROCCA, RV GERNT, PR WEINBERGER, MS HEADLEE, DJ KOHLER, DR GOLDSPIEL, BR PECK, CC MYERS, CE AF COOPER, MR LIEBERMAN, R LAROCCA, RV GERNT, PR WEINBERGER, MS HEADLEE, DJ KOHLER, DR GOLDSPIEL, BR PECK, CC MYERS, CE TI ADAPTIVE-CONTROL WITH FEEDBACK-STRATEGIES FOR SURAMIN DOSING SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID GROWTH-FACTOR RECEPTOR; DOSAGE; TRANSFORMATION; INHIBITION; CELLS; PHARMACOKINETICS; PERFORMANCE; REVERSAL; BINDING; DRUG AB Suramin, a drug used in the treatment of parasitic diseases, is currently being evaluated in clinical trials as an antineoplastic agent. The use of therapeutic drug monitoring and adaptive control with feedback in clinical trials of suramin was initially motivated by an association between acute neurologic toxicity and plasma suramin concentrations in excess of 350-mu-g/ml. We have prospectively examined the performance of both two- and three-compartment population pharmacokinetic models in controlling plasma suramin concentrations and have found that a three-compartment model best describes this drug. No correlation was found between the clearance of suramin and creatinine clearance, as had been previously hypothesized. The low systemic clearance of suramin and the number of parameters required to describe the three-compartment model suggest the need for a bayesian approach to the estimation of individual pharmacokinetics. C1 US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. RP COOPER, MR (reprint author), NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,CLIN PHARMACOL BRANCH,BLDG 10,ROOM 12C103,BETHESDA,MD 20892, USA. NR 41 TC 42 Z9 42 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUL PY 1992 VL 52 IS 1 BP 11 EP 23 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JE053 UT WOS:A1992JE05300004 PM 1623689 ER PT J AU HUESTIS, MA SAMPSON, AH HOLICKY, BJ HENNINGFIELD, JE CONE, EJ AF HUESTIS, MA SAMPSON, AH HOLICKY, BJ HENNINGFIELD, JE CONE, EJ TI CHARACTERIZATION OF THE ABSORPTION PHASE OF MARIJUANA SMOKING SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID DELTA-9-TETRAHYDROCANNABINOL; PERFORMANCE; INTOXICATION AB Rapid blood collection, a paced smoking protocol and timely collection of physiologic and behavioral measures were used to characterize the absorption phase of marijuana smoking. Six healthy males smoked a single marijuana cigarette (placebo, 1.75%, or 3.55% DELTA-9-tetrahydrocannabinol) in a double-blind, randomized, Latin square study design. Rapid blood sampling with a continuous withdrawal pump allowed simultaneous collection with concurrent physiologic and behavioral measures. Mean plasma levels of 7.0 and 18.1 ng/nil DELTA-9-tetrahydrocannabinol were observed after the first inhalation of a 1.75% and 3.55% DELTA-9-tetrahydrocannabinol cigarette, respectively. Blood levels increased rapidly and peaked at 9 minutes, before initiation of the last puff sequence at 9.8 minutes. Three of six subjects reported increases in drug "liking" scores after the first puff, and all subjects responded by the second puff of a high dose cigarette. Significant increases in heart rate and diastolic blood pressure occurred shortly after peak blood levels. Previous studies have indicated that there is a substantial time delay between peak plasma levels of DELTA-9-tetrahydrocannabinol and drug-induced effects. This study showed that behavioral and physiologic effects appear concurrently or within minutes after the rapid appearance of DELTA-9-tetrahydrocannabinol in blood during marijuana smoking. C1 NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224. NR 21 TC 55 Z9 59 U1 1 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUL PY 1992 VL 52 IS 1 BP 31 EP 41 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JE053 UT WOS:A1992JE05300006 PM 1320536 ER PT J AU KOHLER, DR CALIS, KA CORSO, DM AF KOHLER, DR CALIS, KA CORSO, DM TI VALUE OF TRANSDERMAL FENTANYL - REPLY SO CLINICAL PHARMACY LA English DT Letter RP KOHLER, DR (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT PHARM,BLDG 10,ROOM IN-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 0278-2677 J9 CLIN PHARMACY PD JUL PY 1992 VL 11 IS 7 BP 584 EP 585 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HZ764 UT WOS:A1992HZ76400004 ER PT J AU GROSSMAN, E HOFFMAN, A ARMANDO, I ABASSI, Z KOPIN, IJ GOLDSTEIN, DS AF GROSSMAN, E HOFFMAN, A ARMANDO, I ABASSI, Z KOPIN, IJ GOLDSTEIN, DS TI SYMPATHOADRENAL CONTRIBUTION TO PLASMA DOPA (3,4-DIHYDROXYPHENYLALANINE) IN RATS SO CLINICAL SCIENCE LA English DT Article DE DOPA; 6-HYDROXYDOPAMINE; NORADRENALINE; SYMPATHETIC NERVOUS SYSTEM ID CARDIAC-OUTPUT; DIHYDROXYPHENYLALANINE; CATECHOLS; 6-HYDROXYDOPAMINE; HUMANS; SYMPATHECTOMY; EXCRETION; SYSTEM; KIDNEY; BLOOD AB 1. To determine the sources of dopa (3,4-dihydroxyphenylalanine) in plasma, we measured regional arteriovenous differences, tissue concentrations and urinary excretion of dopa during systemic intravenous infusions of l-[H-3]dopa into anaesthetized intact rats and rats pretreated with the sympathetic neurotoxin, 6-hydroxydopamine. 2. In intact rats, large arteriovenous increments in plasma dopa concentrations were noted in the femoral (47%) and adrenal (141%) beds, with a small arterial-portal venous increment (11%), whereas in the kidney there was a substantial (47%) arteriovenous decrement in plasma dopa levels. Skeletal muscle appeared to be a major source of dopa in arterial plasma. 3. Treatment with 6-hydroxydopamine abolished the afferent-efferent increment of plasma dopa concentrations in the femoral bed. The arteriovenous decrement of plasma dopa concentrations in the kidney was preserved, and the arteriovenous increment in the adrenal bed was decreased by about half. Arterial plasma dopa levels fell by 41%. 4. Regional extraction percentages of l-[H-3]dopa were used to estimate the clearances and rates of appearance (spillovers) of dopa in plasma. Dopa spillover was detected in the femoral, renal, splanchnic and adrenal beds, with skeletal muscle accounting for about 44% and the kidneys accounting for about 18% of dopa in arterial plasma. Whereas chemical sympathectomy decreased the femoral and renal spillover of dopa by 90% or more, arterial dopa levels and estimated dopa spillover into arterial plasma were decreased by only about 45%. 5. The kidneys accounted for 22% of dopa clearance from arterial plasma. From the renal extraction of l-[H-3]dopa and the urinary excretion of [H-3]dopamine, it was estimated that 77% of dopa removed in the kidneys was excreted as dopamine in intact animals and 69% was excreted as dopamine in sympathectomized animals. Conversely, about 80% of urinary endogenous dopamine was derived from plasma dopa, regardless of 6-hydroxydopamine treatment. 6. The results indicate that endogenous dopa in arterial plasma is derived susbstantially but not exclusively from sympathetic nerve endings that are destroyed by 6-hydroxydopamine, especially in skeletal muscle and the kidneys. Regional dopa spillover therefore probably reflects regional catecholamine biosynthesis. In rats, urinary dopamine is derived mainly from renal decarboxylation of circulating dopa. C1 NINCDS,CLIN NEUROSCI BRANCH,ROOM 5N262,BLDG 10,BETHESDA,MD 20892. NHLBI,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. NR 33 TC 27 Z9 27 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0143-5221 J9 CLIN SCI JI Clin. Sci. PD JUL PY 1992 VL 83 IS 1 BP 65 EP 74 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JD536 UT WOS:A1992JD53600010 PM 1325324 ER PT J AU KEENAN, TW HUANG, CM ZIERDT, CH AF KEENAN, TW HUANG, CM ZIERDT, CH TI COMPARATIVE-ANALYSIS OF LIPID-COMPOSITION IN AXENIC STRAINS OF BLASTOCYSTIS-HOMINIS SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article ID EPIDEMIOLOGY; INFECTION; PROTOZOAN AB 1. Six axenic strains of Blastocystis hominis varied in content of lipids from 12 to 43 pg total lipid/cell. With all strains, phospholipid content was about 39% of total lipids. 2. Neutral lipid fractions of B. hominis were resolved into nine constituents, of which seven were identified tentatively. Sterol esters, principally esters of cholesterol, were the major neutral lipid constituent, accounting for 49- 63% of the neutral lipids, and at least 30% of the total lipids. 3. Polar lipids were resolved into eleven constituents, of which nine were identified tentatively. Phosphatidylcholine was the major polar lipid constituent of all strains, accounting for 53-63% of the polar lipids, and about 22% of the total lipids. C1 THOMAS JEFFERSON UNIV,DEPT PATHOL,PHILADELPHIA,PA 19107. NIH,DEPT CLIN PATHOL,MICROBIOL SERV,BETHESDA,MD 20205. RP KEENAN, TW (reprint author), VIRGINIA POLYTECH INST & STATE UNIV,DEPT BIOCHEM,BLACKSBURG,VA 24061, USA. FU NIGMS NIH HHS [GM31244] NR 21 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0305-0491 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD JUL PY 1992 VL 102 IS 3 BP 611 EP 615 DI 10.1016/0305-0491(92)90055-V PG 5 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA JC948 UT WOS:A1992JC94800023 PM 1499298 ER PT J AU WEINBACH, EC LEVENBOOK, L ALLING, DW AF WEINBACH, EC LEVENBOOK, L ALLING, DW TI BINDING OF TRICYCLIC ANTIDEPRESSANT DRUGS TO TROPHOZOITES OF GIARDIA-LAMBLIA SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-PHARMACOLOGY TOXICOLOGY & ENDOCRINOLOGY LA English DT Article ID AFFINITY BINDING; RIBOSOMAL-RNA; IMIPRAMINE; GROWTH; IMIPRAMINE; PLATELETS; PROTEIN; INVITRO; AGENTS; SITES AB 1. Parameters affecting the binding of the tricyclic drugs imipramine and 3-chloroimipramine to Giardia lamblia trophozoites were studied. 2. Two to three times more chlorimipramine than imipramine was bound, consistent with a similar difference in suppressing parasite growth (Weinbach et al., 1985). 3. Kinetic analysis and the ease with which bound drugs can be washed out of the parasites indicate that noncovalent forces are involved in the drug-parasite interaction. 4. Evidence is presented that such drugs probably bind to parasite protein at common binding sites. 5. The data relate to our earlier observation that chlorimipramine is about ten times more effective than metronidazole (Crouch et al., 1986) in suppressing G. lamblia growth in vitro. Tricyclic drugs, therefore, merit serious consideration as novel therapeutic agents against giardiasis. RP WEINBACH, EC (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 25 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0742-8413 J9 COMP BIOCHEM PHYS C JI Comp. Biochem. Physiol. C-Pharmacol. Toxicol. Endocrinol. PD JUL PY 1992 VL 102 IS 3 BP 391 EP 396 DI 10.1016/0742-8413(92)90131-P PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Toxicology; Zoology SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Toxicology; Zoology GA JQ720 UT WOS:A1992JQ72000008 PM 1360349 ER PT J AU LYNE, A BOSTON, R PETTIGREW, K ZECH, L AF LYNE, A BOSTON, R PETTIGREW, K ZECH, L TI EMSA - A SAAM SERVICE FOR THE ESTIMATION OF POPULATION PARAMETERS BASED ON MODEL FITS TO IDENTICALLY REPLICATED EXPERIMENTS SO COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE LA English DT Article DE MULTIPLE STUDIES; MODELING; SAAM; KINETICS; MAXIMUM LIKELIHOOD; ESTIMATION AB This paper presents a new technique for the aggregation of models to produce population parameter estimates based on a set of identically replicated experiments. After describing the theoretical basis for the technique we discuss tactical and strategic issues associated with its implementation in the SAAM software. Finally, we demonstrate its utility in the aggregation of models fitted to four simulated experiments. C1 NIH,MATH BIOL LAB,BLDG 10,RM 6B13,BETHESDA,MD 20892. MURDOCH UNIV,COMP SERV UNIT,MURDOCH,WA 6150,AUSTRALIA. UNIV PENN,NEW BOLTON CTR,KENNETT SQ,PA 19348. NIMH,BETHESDA,MD 20892. NR 38 TC 27 Z9 27 U1 1 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-2607 J9 COMPUT METH PROG BIO JI Comput. Meth. Programs Biomed. PD JUL PY 1992 VL 38 IS 2-3 BP 117 EP 151 DI 10.1016/0169-2607(92)90082-I PG 35 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA JZ134 UT WOS:A1992JZ13400005 PM 1458864 ER PT J AU CANNON, RO AF CANNON, RO TI THE CORONARY MICROCIRCULATION IN HEART-DISEASE - HYPERTROPHIC CARDIOMYOPATHY, HYPERTENSION, AND MICROVASCULAR ANGINA SO CORONARY ARTERY DISEASE LA English DT Review DE ANGINA PECTORIS; CORONARY CIRCULATION; CARDIOMYOPATHY; HYPERTENSION; HYPERTROPHY ID MYOCARDIAL PERFUSION ABNORMALITIES; LEFT-VENTRICULAR HYPERTROPHY; VASODILATOR RESERVE; FLOW RESERVE; ARTERY DISEASE; CHEST PAIN; SYNDROME-X; PECTORIS; HEMODYNAMICS; METABOLISM RP CANNON, RO (reprint author), NHLBI,CARDIOL BRANCH,BLDG 10,ROOM 7B-15,BETHESDA,MD 20892, USA. NR 37 TC 3 Z9 3 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0954-6928 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD JUL PY 1992 VL 3 IS 7 BP 555 EP 563 DI 10.1097/00019501-199207000-00002 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JJ145 UT WOS:A1992JJ14500002 ER PT J AU HOLLENBERG, SM CUNNION, RE PARRILLO, JE AF HOLLENBERG, SM CUNNION, RE PARRILLO, JE TI EFFECT OF SEPTIC SERUM ON VASCULAR SMOOTH-MUSCLE - INVITRO STUDIES USING RAT AORTIC RINGS SO CRITICAL CARE MEDICINE LA English DT Article DE SHOCK, SEPTIC; AORTA, THORACIC; TUMOR NECROSIS FACTOR; VASODILATION; VASCULAR RESISTANCE; CATECHOLAMINES; NOREPINEPHRINE; ENDOTHELIUM; INFECTION ID TUMOR-NECROSIS-FACTOR; SHOCK; CONTRACTILITY; DYSFUNCTION; ENDOTHELIUM; ENDOTOXIN; SEPSIS; HUMANS AB Background and Methods. Septic shock in humans is characterized by hypotension, low systemic vascular resistance, and high cardiac output. We hypothesized that circulating vasodilatory substances are, in part, responsible for this low systemic vascular resistance. To investigate this possibility, we exposed isolated rat aortic rings to sera from patients with septic shock and to sera from dogs made septic by intraperitoneal implantation of infected clots. Isolated rings from rat thoracic aortas were mounted on hooks in chambers filled with modified Krebs' buffer and bubbled with 95% oxygen/5% CO2. After documentation of functional endothelium, the rings were precontracted with norepinephrine. Serum was then added and ring tension measured continuously over the next 20 mins. Results: Sera from normal humans increased ring tension by 6% (60 +/- 39 [SEM] mg tension/mg ring). Sera from nine patients with septic shock decreased tension by 30% (350 +/- 42 mg tension/mg ring; p < .001). In response to sera from control dogs, tension increased by 16% (122 +/- 37 mg tension/mg ring). In contrast, septic dog sera caused tension to decrease by 36% (278 +/- 38 mg tension/mg ring; p <.001).Vasodilation was unaffected when the septic patient and dog sera were dialyzed to remove molecules <10,000 molecular weight. Chemical deendothelialization with sodium deoxycholate also did not affect the vasodilatory response to septic patient or dog sera. Conclusions: Septic sera can relax rat aortic smooth muscle. Dialyzing to exclude the effects of small molecules and removing the endothelium did not eliminate this vasodilatory response. These data suggest the presence in septic serum of circulating substances capable of relaxing vascular smooth muscle that may play an important role in the pathogenesis of the cardiovascular abnormalities in septic shock. C1 NIH,CTR CLIN,DEPT CRIT CARE MED,BLDG 10,ROOM 7-D-43,BETHESDA,MD 20892. RUSH PRESBYTERIAN ST LUKES MED CTR,RUSH HEART INST,CHICAGO,IL 60612. NR 17 TC 15 Z9 15 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUL PY 1992 VL 20 IS 7 BP 993 EP 998 DI 10.1097/00003246-199207000-00016 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA JD804 UT WOS:A1992JD80400016 PM 1617994 ER PT J AU SILVERMAN, HJ VINICKY, JK GASNER, MR AF SILVERMAN, HJ VINICKY, JK GASNER, MR TI ADVANCE DIRECTIVES - IMPLICATIONS FOR CRITICAL CARE SO CRITICAL CARE MEDICINE LA English DT Article DE ADVANCE DIRECTIVES; LIVING WILLS; DURABLE POWER OF ATTORNEY; RIGHT TO DIE; ETHICS; LIFE-SUPPORT SYSTEMS; MECHANICAL VENTILATION; CARDIOPULMONARY RESUSCITATION; TERMINAL CARE ID CARDIOPULMONARY RESUSCITATION; FAMILY ATTITUDES; LIVING WILLS; LIFE; PHYSICIAN; PATIENT; OUTPATIENTS; CHOICES; ORDERS; NURSE AB Objective. To discuss the relative merits and limitations of living wills and the durable power of attorney for health care. Data Sources: Computerized search of MEDLINE. Study Selection: Studies involving treatment decisions at the end of life and descriptive articles on advance directives. Results: The recent Cruzan case and passage of the Patient Self-Determination Act have led to an ethical and legal recognition of advance directives, and therefore, critical care practitioners must be familiar with these documents. A living will is a mechanism by which patients can communicate their desires for medical treatment at the end of life. However, the condition that patients be in a "terminal condition," the inability to predict every possible clinical circumstance, and linguistic vagueness have limited the usefulness of living wills. The durable power of attorney for health care overcomes the inherent restrictive weaknesses of living wills, because informed decisions are made by people based on their knowledge of the patient's beliefs and the nuance of the clinical scenario. A concern with this advance directive is that some patients may not know a suitable person to appoint or that the chosen agent may not be available. Conclusions: We recommend the execution of both a living will and a durable power of attorney for health care to provide the best assurance that patients' desires concerning medical treatments will be respected. C1 UNIV MARYLAND,SCH MED,DIV PULM & CRIT CARE MED,BALTIMORE,MD 21201. NIH,BIOETH PROGRAM,BETHESDA,MD 20892. SOC RIGHT DIE,NEW YORK,NY. NR 28 TC 8 Z9 8 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUL PY 1992 VL 20 IS 7 BP 1027 EP 1031 DI 10.1097/00003246-199207000-00021 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA JD804 UT WOS:A1992JD80400021 PM 1617972 ER PT J AU DATILES, MB SCHUMER, DJ ZIGLER, JS RUSSELL, P ANDERSON, L GARLAND, D AF DATILES, MB SCHUMER, DJ ZIGLER, JS RUSSELL, P ANDERSON, L GARLAND, D TI 2-DIMENSIONAL GEL-ELECTROPHORETIC ANALYSIS OF HUMAN LENS PROTEINS SO CURRENT EYE RESEARCH LA English DT Article ID BETA-CRYSTALLINS; TISSUE PROTEINS; CELL FRACTIONS; GENE; SERUM AB Human lens proteins from clear lenses were separated and identified using two-dimensional polyacrylamide electrophoresis. Isoelectric focusing, both equilibrium and non-equilibrium, was performed in the first dimension and SDS electrophoresis in the second dimension. Proteins were identified by Western blotting and sequencing techniques and by comparison with patterns obtained with purified crystallin fractions. Analyses were performed on total urea soluble proteins of lenses varying,in age from fetal to 73 yr. Several hundred protein spots representing crystallins, cytoskeletal proteins and enzymes were resolved in the fetal lens. In the older lenses there was a dramatic increase in the number of protein species in the molecular weight range of the crystallins and a reduced number of discrete protein species visible at molecular weights greater than 50,000. Conversely, a number of proteins below approximately 15 kDa were visible even in the fetal lens. The number and amount of polypeptides in this molecular weight range were increased in the older lenses. Many of these low molecular weight species could be assigned to either the alpha-, beta- or gamma-crystallin fractions. An age dependent increase in the number of acidic species of both crystallins and other proteins, such as, glyceraldehyde 3-phosphate dehydrogenase was observed as well as the loss or mobility change of gamma-crystallin. Two-dimensional gel electrophoresis provides a sensitive and practical technique for characterizing all of the proteins of the human lens. C1 NEI,9000 ROCKVILLE PIKE,BLDG 6,ROOM 235,BETHESDA,MD 20892. HENRY FORD HOSP,DEPT OPHTHALMOL,DETROIT,MI 48202. LARGE SCALE BIOL CORP,ROCKVILLE,MD. NR 24 TC 28 Z9 33 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD JUL PY 1992 VL 11 IS 7 BP 669 EP 677 DI 10.3109/02713689209000740 PG 9 WC Ophthalmology SC Ophthalmology GA JG093 UT WOS:A1992JG09300008 PM 1521468 ER PT J AU SCHUMACHER, GE EICHMILLER, FC ANTONUCCI, JM AF SCHUMACHER, GE EICHMILLER, FC ANTONUCCI, JM TI EFFECTS OF SURFACE-ACTIVE RESINS ON DENTIN COMPOSITE BONDS SO DENTAL MATERIALS LA English DT Article ID HARD TOOTH TISSUES; N-PHENYLGLYCINE; ADHESIVE; STRENGTH; SYSTEM AB Effective dentin bonding systems based on para-PMDM diadduct of pyromellitic dianhydride and 2-hydroxyethyl methacrylate (HEMA) have been developed (Bowen et al, 1982). Para-PMDM, a solid of limited solubility, is usually applied from an acetone solution to dentin that has been preconditioned with acid and N-phenylglycine. The feasibility of using a liquid, surface-active bonding resin to substitute for or to supplement para-PMDM was explored. Mono(2-methacryloyloxy)ethyl phthalate (MMEP), a liquid, monofunctional homolog of para-PMDM (derived from the reaction of phthalic anhydride with HEMA) was used to formulate several bonding resin systems and solutions. Dentin surfaces were pretreated according to several variations of a three-step bonding protocol involving sequential application of 6.8 w/o ferric oxalate in 2.5 w/o HNO3, N-phenylglycine in acetone, and an experimental bonding resin before placement of a chemically cured composite restorative material. Tensile bond strengths were tested after 24 h storage in distilled water at 23-degrees-C. The results suggest that solutions based on MMEP and/or para-PMDM in acetone or in other monomers, especially those containing HEMA, can effectively promote bonding to dentin. A new mechanism for the observed self-polymerization of MMEP or para-PMDM with N-phenylglycine is proposed. C1 NATL INST STAND & TECHNOL,DIV POLYMERS,DENT & MED MAT GRP,GAITHERSBURG,MD 20899. NIH,COMMISSIONED OFFICERS DENT CLIN,CTR CLIN,BETHESDA,MD 20892. AMER DENT ASSOC,HLTH FDN,PAFFENBARGER RES CTR,CHICAGO,IL 60611. RI Rastelli, Marcio/B-8034-2011 FU NIDCR NIH HHS [Y01-DE30001] NR 22 TC 22 Z9 22 U1 0 U2 1 PU ACAD DENTAL MATERIALS PI DALLAS PA BAYLOR COLLEGE DENTISTRY, 3302 GASTON AVE, DALLAS, TX 75266-0677 SN 0109-5641 J9 DENT MATER JI Dent. Mater. PD JUL PY 1992 VL 8 IS 4 BP 278 EP 282 DI 10.1016/0109-5641(92)90100-Q PG 5 WC Dentistry, Oral Surgery & Medicine; Materials Science, Biomaterials SC Dentistry, Oral Surgery & Medicine; Materials Science GA JV634 UT WOS:A1992JV63400013 PM 1291398 ER PT J AU CLARKE, HJ OBLIN, C BUSTIN, M AF CLARKE, HJ OBLIN, C BUSTIN, M TI DEVELOPMENTAL REGULATION OF CHROMATIN COMPOSITION DURING MOUSE EMBRYOGENESIS - SOMATIC HISTONE H1 IS 1ST DETECTABLE AT THE 4-CELL STAGE SO DEVELOPMENT LA English DT Article DE HISTONE H1; MOUSE; OOCYTE; EMBRYOGENESIS; CHROMATIN ID MESSENGER-RNA DEGRADATION; PREIMPLANTATION DEVELOPMENT; NUCLEAR TRANSPLANTATION; MEIOTIC MATURATION; EMBRYONIC CONTROL; GENE-EXPRESSION; PROTEIN; INVITRO; DNA; TRANSITION AB We have examined the distribution of histone H1 in oocytes and preimplantation embryos of the mouse, using a polyclonal antibody raised against the histone H1 subtypes present in somatic cells. Immunofluorescence and immunoblotting analyses failed to detect somatic histone H1 in germinal vesicle (GV)-stage oocytes. In contrast, somatic histone H1 was detectable by immunofluorescence in the nuclei of GV oocytes previously injected with histone H1 as well as the nuclei of ovarian granulosa cells, and by immunoblotting in 8-cell embryos. 1- and 2-cell embryos examined by immuofluorescence did not contain detectable somatic histone H1. At the early 4-cell stage (54-56 hours post-hCG), 5 of 52 embryos contained somatic histone H1 in one or more nuclei. By the late 4-cell stage (66-68 hours post-hCG), however, 58 of 62 embryos contained somatic histone H1. In 8-cell embryos, morulae and blastocysts, all nuclei contained somatic histone H1 in every case. When embryos were exposed to the transcriptional inhibitor, alpha-amanitin, beginning at the late 2-cell stage, they cleaved to the 4-cell stage but fewer than 10% developed histone H1 immunoreactivity. When treatment began at the early 4-cell stage, the embryos that remained at the 4-cell stage in the presence of the drug developed histone H1 immunoreactivity in half of the cases. Embryos that reached the 5- to 8-cell stage in the presence of the drug developed histone H1 immunoreactivity in every case. The protein synthesis inhibitor, puromycin, prevented development of histone H1 immunoreactivity in most embryos when added either at the late 2-cell or early 4-cell stage. When embryos were exposed to the DNA replication inhibitor, aphidicolin, beginning at the late 2-cell stage, they cleaved to the 4-cell stage, but developed only a very weak histone H1 immunoreactivity. These results indicate that oocytes and 1- and 2-cell embryos contain little or no somatic histone H1, which may imply that these cells contain immunologically distinct histone H1 subtypes. The somatic subtypes first appear at the 4-cell stage, through a process requiring embryonic transcription and DNA replication during the third cell cycle. These results suggest that the deposition of somatic histone H1 on chromatin is developmentally regulated during mouse embryogenesis. C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. MCGILL UNIV,DEPT BIOL,MONTREAL H3A 2T5,QUEBEC,CANADA. MCGILL UNIV,DEPT OBSTET & GYNAECOL,MONTREAL H3A 2T5,QUEBEC,CANADA. RI Bustin, Michael/G-6155-2015 NR 42 TC 75 Z9 77 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD JUL PY 1992 VL 115 IS 3 BP 791 EP 799 PG 9 WC Developmental Biology SC Developmental Biology GA JG755 UT WOS:A1992JG75500015 PM 1425354 ER PT J AU HARRIS, LL TALIAN, JC ZELENKA, PS AF HARRIS, LL TALIAN, JC ZELENKA, PS TI CONTRASTING PATTERNS OF C-MYC AND N-MYC EXPRESSION IN PROLIFERATING, QUIESCENT, AND DIFFERENTIATING CELLS OF THE EMBRYONIC CHICKEN LENS SO DEVELOPMENT LA English DT Article DE PROTOONCOGENES; C-MYC; N-MYC; CHICK; LENS; MESSENGER RNA ID POLYMERASE CHAIN-REACTION; DNA-BINDING; MESSENGER-RNA; ONCOGENE; PROTEINS; SEQUENCE; PROTOONCOGENE; GENE; AMPLIFICATION; QUANTITATION AB The present study uses the polymerase chain reaction and in situ hybridization to examine c-myc and N-myc mRNA in the embryonic chicken lens at 6,10,14 and 19 days of development and compares the pattern of expression obtained with the developmental pattern of cell proliferation and differentiation. In the central epithelium, c-myc mRNA levels were proportional to the percentage of proliferating cells throughout development. N-myc mRNA expression in this region was relatively low and showed no correlation with cell proliferation. The ratio of N-myc to c-myc mRNA increased markedly with the onset of epithelial cell elongation and terminal fiber cell differentiation, although both c-myc and N-myc mRNAs continued to be expressed in postmitotic, elongating cells of the equatorial epithelium and in terminally differentiating lens fiber cells. Thus, increased expression of N-myc, a gene whose protein product may compete with c-myc protein for dimerization partners, accompanies the dissociation of c-myc expression and cell proliferation during terminal differentiation of lens fiber cells. C1 NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892. NIH,HOWARD HUGHES MED INST,RES SCHOLARS PROGRAM,BETHESDA,MD 20814. NR 40 TC 32 Z9 33 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 0950-1991 J9 DEVELOPMENT JI Development PD JUL PY 1992 VL 115 IS 3 BP 813 EP 820 PG 8 WC Developmental Biology SC Developmental Biology GA JG755 UT WOS:A1992JG75500017 PM 1339339 ER PT J AU NAKAGAWA, M TETI, DM LAMB, ME AF NAKAGAWA, M TETI, DM LAMB, ME TI AN ECOLOGICAL STUDY OF CHILD MOTHER ATTACHMENTS AMONG JAPANESE SOJOURNERS IN THE UNITED-STATES SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID SOCIAL SUPPORT; MARITAL QUALITY; STRESS; ADJUSTMENT; EXPERIENCE; MARRIAGE; FAMILY AB This study examined the effects of life stress and support on parenting and attachment security among 53 Japanese mothers and their preschoolers who were temporarily living in the U.S. Mothers who had been in the U.S. for 6 months or less reported more life stress and less social support than did mothers who had been in the U.S. for more than 6 months. Measures of life stress and support were differently related to measures of parenting stress and security of attachment. When life stress was high, mothers reported more parenting stress if support was not adequate and less parenting stress if support was adequate. High support, particularly high marital support, was associated with lower levels of attachment security. The findings call for further research on family dynamics-particularly on the interplay between the husband-wife and mother-child subsystems-to develop ecological models of Japanese parenting and child development. C1 UNIV MARYLAND,DEPT PSYCHOL,CATONSVILLE,MD 21228. NICHHD,BETHESDA,MD 20892. NR 54 TC 16 Z9 16 U1 0 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD JUL PY 1992 VL 28 IS 4 BP 584 EP 592 PG 9 WC Psychology, Developmental SC Psychology GA JC407 UT WOS:A1992JC40700007 ER PT J AU BORNSTEIN, MH TAL, J RAHN, C GALPERIN, CZ LAMOUR, M OGINO, M PECHEUX, MG TODA, S AZUMA, H TAMISLEMONDA, CS AF BORNSTEIN, MH TAL, J RAHN, C GALPERIN, CZ LAMOUR, M OGINO, M PECHEUX, MG TODA, S AZUMA, H TAMISLEMONDA, CS TI FUNCTIONAL-ANALYSIS OF THE CONTENTS OF MATERNAL SPEECH TO INFANTS OF 5 AND 13 MONTHS IN 4 CULTURES - ARGENTINA, FRANCE, JAPAN, AND THE UNITED-STATES SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID PRELINGUAL INFANTS; PRAGMATIC ANALYSIS; MOTHERS SPEECH; CONVERSATION; BEHAVIOR AB Maternal speech to infants of 2 ages in 4 cultures was examined to probe how infant age and cultural variation influence the contents of that speech. Argentine, French, Japanese, and U.S. American mothers were individually videotaped in naturalistic free-play interactions at home with their 5- and 13-month-old infants, maternal speech was transcribed, and the contents classified as affect salient or information salient. Mothers in the 4 cultures use all speech categories to young infants, speak to older infants more than to younger infants, but differ in the emphasis of their speech. Similarities speak to the universality of maternal speech to infants, provoked perhaps by infants' common psychological status; differences in the speech mothers choose to emphasize speak perhaps to the expression of cultural preferences. C1 UNIV BELGRANO,BUENOS AIRES,ARGENTINA. FDN ADOLPHE DE ROTHSCHILD,PARIS,FRANCE. SOPHIA UNIV,TOKYO 102,JAPAN. UNIV PARIS 07,F-75221 PARIS 05,FRANCE. SHIRAYURI COLL,TOKYO,JAPAN. CNRS,F-75005 PARIS,FRANCE. NYU,NEW YORK,NY 10003. RP BORNSTEIN, MH (reprint author), NICHHD,BLDG 31,ROOM B2B15,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 72 TC 71 Z9 73 U1 0 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD JUL PY 1992 VL 28 IS 4 BP 593 EP 603 DI 10.1037//0012-1649.28.4.593 PG 11 WC Psychology, Developmental SC Psychology GA JC407 UT WOS:A1992JC40700008 ER PT J AU EASTMAN, RC CARSON, RE JACOBSON, KA SHAI, Y CHANNING, MA DUNN, BB BACHER, JD BAAS, E JONES, E KIRK, KL LESNIAK, MA ROTH, J AF EASTMAN, RC CARSON, RE JACOBSON, KA SHAI, Y CHANNING, MA DUNN, BB BACHER, JD BAAS, E JONES, E KIRK, KL LESNIAK, MA ROTH, J TI INVIVO IMAGING OF INSULIN-RECEPTORS IN MONKEYS USING F-18 LABELED INSULIN AND POSITRON EMISSION TOMOGRAPHY SO DIABETES LA English DT Article ID DEGRADATION; I-125-INSULIN; METABOLISM; PROTEINS; BINDING; RATS; BILE AB We previously described a prosthetic group methodology for incorporating F-18 into peptides and showed that F-18-labeled insulin (F-18-insulin) binds to insulin receptors on human cells (IM-9 lymphoblastoid cells) with affinity equal to that of native insulin (1). We now report studies using F-18-insulin with positron emission tomography to study binding to insulin receptors in vivo. Positron emission tomography scans were performed in six rhesus monkeys injected with 0.3-1.4 mCi of F-18-insulin (approximately 0.1 nmol, SA 4-11 Ci/mu-mol). Integrity of the tracer in blood, determined by immunoprecipitation, was 94% of control for the first 5 min and decreased to 31% by 30 min. Specific, saturable uptake of F-18 was observed in the liver and kidney. Coinjection of unlabeled insulin (200 U, approximately 1 nmol) with the F-18-insulin reduced liver and increased kidney uptake of the labeled insulin. Liver radioactivity was decreased by administration of unlabeled insulin at 3 min, but not 5 min, after administration of the tracer, while some kidney radioactivity could be displaced 5 min after injection. Clearance of F-18 was predominantly in bile and urine. F-18-insulin is a suitable analogue for studying insulin receptor-ligand interactions in vivo, especially in the liver and kidney. C1 NIADDKD,BIOORGAN CHEM LAB,DIABET BRANCH,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BETHESDA,MD 20892. JOHNS HOPKINS ASTHMA & ALLERGY CTR,DIV GERIATR MED & GERONTOL,BALTIMORE,MD. WARREN GRANT MAGNUSON CLIN CTR,DEPT POSITRON EMISSION TOMOGRAPHY,BETHESDA,MD. WEIZMANN INST SCI,DEPT MEMBRANE RES,IL-76100 REHOVOT,ISRAEL. RI Carson, Richard/H-3250-2011; Jacobson, Kenneth/A-1530-2009 OI Carson, Richard/0000-0002-9338-7966; Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031115-24, Z99 DK999999] NR 17 TC 14 Z9 14 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 1992 VL 41 IS 7 BP 855 EP 860 DI 10.2337/diabetes.41.7.855 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HZ793 UT WOS:A1992HZ79300012 PM 1612200 ER PT J AU HARRIS, MI KLEIN, R WELBORN, TA KNUIMAN, MW AF HARRIS, MI KLEIN, R WELBORN, TA KNUIMAN, MW TI ONSET OF NIDDM OCCURS AT LEAST 4-7 YR BEFORE CLINICAL-DIAGNOSIS SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; NON-HISPANIC WHITES; UNITED-STATES POPULATION; DIABETIC-RETINOPATHY; PLASMA-GLUCOSE; BLOOD-PRESSURE; PIMA-INDIANS; RISK-FACTORS; MEXICAN-AMERICANS; PREVALENCE AB OBJECTIVE - To investigate duration of the period between diabetes onset and its clinical diagnosis. RESEARCH DESIGN AND METHODS - Two population-based groups of white patients with non-insulin-dependent diabetes (NIDDM) in the United States and Australia were studied. Prevalence of retinopathy and duration of diabetes subsequent to clinical diagnosis were determined for all subjects. Weighted linear regression was used to examine the relationship between diabetes duration and prevalence of retinopathy. RESULTS - Prevalence of retinopathy at clinical diagnosis of diabetes was estimated to be 20.8% in the U.S. and 9.9% in Australia and increased linearly with longer duration of diabetes. By extrapolating this linear relationship to the time when retinopathy prevalence was estimated to be zero, onset of detectable retinopathy was calculated to have occurred approximately 4-7 yr before diagnosis of NIDDM. Because other data indicate that diabetes may be present for 5 yr before retinopathy becomes evident, onset of NIDDM may occur 9-12 yr before its clinical diagnosis. CONCLUSIONS - These findings suggest that undiagnosed NIDDM is not a benign condition. Clinically significant morbidity is present at diagnosis and for years before diagnosis. During this preclinical period, treatment is not being offered for diabetes or its specific complication's, despite the fact that reduction in hyperglycemia, hypertension, and cardiovascular risk factors is believed to benefit patients. Imprecise dating of diabetes onset also obscures investigations of the etiology of NIDDM and studies of the nature and importance of risk factors for diabetes complications. C1 UNIV WISCONSIN, SCH MED, DEPT OPHTHALMOL, MADISON, WI 53706 USA. UNIV WESTERN AUSTRALIA, DEPT MED, PERTH, WA, AUSTRALIA. RP HARRIS, MI (reprint author), NIDDK, NATL DIABET DATA GRP, WESTWOOD BLDG, ROOM 620, BETHESDA, MD 20892 USA. RI Knuiman, Matthew/I-5549-2013 FU NEI NIH HHS [EY-03083] NR 40 TC 744 Z9 767 U1 3 U2 17 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 1992 VL 15 IS 7 BP 815 EP 819 DI 10.2337/diacare.15.7.815 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HZ646 UT WOS:A1992HZ64600001 PM 1516497 ER PT J AU CHANG, YJ MCCABE, RT RENNERT, H BUDARF, ML SAYEGH, R EMANUEL, BS SKOLNICK, P STRAUSS, JF AF CHANG, YJ MCCABE, RT RENNERT, H BUDARF, ML SAYEGH, R EMANUEL, BS SKOLNICK, P STRAUSS, JF TI THE HUMAN PERIPHERAL-TYPE BENZODIAZEPINE RECEPTOR - REGIONAL MAPPING OF THE GENE AND CHARACTERIZATION OF THE RECEPTOR EXPRESSED FROM CDNA SO DNA AND CELL BIOLOGY LA English DT Article ID BINDING-SITES; HUMAN CHROMOSOME-22; MOLECULAR-CLONING; PINEAL-GLAND; MEMBRANES; LOCALIZATION; CELLS; MAP; CHOLESTEROL; PROTEIN AB A cDNA for the human "peripheral-type" benzodiazepine receptor (PBR) was isolated from a liver cDNA library. The 851-nucleotide probe hybridized with a approximately 1 kb mRNA in Northern blots of RNA extracted from various human tissues and cell lines. The human PBR probe was hybridized to DNA from a somatic cell hybrid mapping panel to determine that the gene maps to chromosome 22. With a regional mapping panel for chromosome 22, we localized the gene within band 22q13.31. The ligand-binding properties of the receptor expressed from the cDNA were examined in transient expression experiments and compared to the endogenous human PBR. The PBR ligand [H-3]PK 11195 had high affinity for the expressed receptor in COS-1 cells, but the affinities of a pair of isoquinoline propanamide enantiomers differed remarkably in expressed and endogenous human PBR. These findings reveal that the host cell and/or post-translational modification may have an important influence on PBR function. C1 UNIV PENN,SCH MED,DEPT OBSTET & GYNECOL,771 CLIN RES BLDG,422 CURIE BLVD,PHILADELPHIA,PA 19104. NIDDK,NEUROSCI LAB,BETHESDA,MD 20892. CHILDRENS HOSP PHILADELPHIA,DIV HUMAN GENET & MOLEC BIOL,PHILADELPHIA,PA 19104. FU NCI NIH HHS [CA-39926]; NHGRI NIH HHS [HG-00425]; NICHD NIH HHS [HD-06274] NR 39 TC 25 Z9 25 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD JUL-AUG PY 1992 VL 11 IS 6 BP 471 EP 480 DI 10.1089/dna.1992.11.471 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA JE967 UT WOS:A1992JE96700006 PM 1326278 ER PT J AU SMITH, SJ KORZEKWA, KR AOYAMA, T GONZALEZ, FJ DARBYSHIRE, JF SUGIYAMA, K GILLETTE, JR AF SMITH, SJ KORZEKWA, KR AOYAMA, T GONZALEZ, FJ DARBYSHIRE, JF SUGIYAMA, K GILLETTE, JR TI 12-ALPHA-HYDROXYTESTOSTERONE - A HITHERTO UNIDENTIFIED TESTOSTERONE METABOLITE PRODUCED BY CYTOCHROME-P-450 2A2 SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID HEPATIC-MICROSOMAL CYTOCHROME-P-450; CDNA-DIRECTED EXPRESSION; RAT-LIVER MICROSOMES; AMINO-ACID SEQUENCE; CATALYTIC ACTIVITY; STEROID-HORMONES; PURIFICATION; 7-ALPHA-HYDROXYLASE; ISOZYMES; FORMS AB Several cytochrome P-450 enzymes are able to hydroxylate testosterone to many different metabolites, some of which remain to be identified. One hitherto unidentified metabolite represents a major metabolite of P-450 2A2, present in the liver of adult male rats, and a minor metabolite of several other cytochrome P-450 enzymes. Using the techniques of HPLC and GC/MS, we have obtained unequivocal evidence that this metabolite is 12-alpha-hydroxytestosterone. C1 NHLBI,CHEM PHARMACOL LAB,BETHESDA,MD 20892. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 34 TC 11 Z9 11 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD JUL-AUG PY 1992 VL 20 IS 4 BP 566 EP 571 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JE286 UT WOS:A1992JE28600017 PM 1356736 ER PT J AU LYMAN, CA WALSH, TJ AF LYMAN, CA WALSH, TJ TI SYSTEMICALLY ADMINISTERED ANTIFUNGAL AGENTS - A REVIEW OF THEIR CLINICAL-PHARMACOLOGY AND THERAPEUTIC APPLICATIONS SO DRUGS LA English DT Review ID AMPHOTERICIN-B NEPHROTOXICITY; ACQUIRED IMMUNODEFICIENCY SYNDROME; LIPOSOME-ENCAPSULATED NYSTATIN; HIGH-DOSE KETOCONAZOLE; FUNGAL-INFECTIONS; CANDIDA-ALBICANS; CEREBROSPINAL-FLUID; TISSUE PENETRATION; CANCER-PATIENTS; PHARMACOKINETIC PROPERTIES AB Systemic antifungal agents express great diversity in their pharmacokinetic profiles, mechanisms of action, and toxicities. Understanding the diverse pharmacokinetic properties of systemic antifungals is critical to their appropriate application. Amphotericin B, drug of choice for most invasive mycoses, has unique pharmacokinetic properties, binding initially to serum lipoproteins and redistributing from blood to tissues. Dosing recommendations are based on the specific infection and the status of the host. Lipid formulations of amphotericin B may be able to attenuate some of its toxicities. Flucytosine is a water-soluble, fluorinated pyrimidine that possesses excellent bioavailability. It is administered only in combination with amphotericin B because of frequent development of secondary drug resistance, and is associated with dose-dependent bone marrow suppression. The antifungal azoles are relatively well tolerated, have broad spectrum antifungal activity, and are fungistatic in vitro. Ketonconazole and itraconazole are highly bound to plasma proteins, are extensively metabolised by the liver, and are relatively insoluble in aqueous solution. By comparison, fluconazole is only weakly bound to serum proteins, is relatively stable to metabolic conversion, and is water soluble. Fluconazole penetrates the cerebrospinal fluid well and is approved for primary and suppressive therapy of cryptococcal meningitis in AIDS patients. The echinocandins have a narrow spectrum of antifungal activity, being effective only against Candida spp. C1 NCI,PEDIAT BRANCH,INFECT DIS SECT,BLDG 10,ROOM 13N240,BETHESDA,MD 20892. NR 238 TC 177 Z9 184 U1 1 U2 4 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PD JUL PY 1992 VL 44 IS 1 BP 9 EP 35 DI 10.2165/00003495-199244010-00002 PG 27 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA JD539 UT WOS:A1992JD53900003 PM 1379913 ER PT J AU WHEELER, D LIN, JH CHRAMBACH, A AF WHEELER, D LIN, JH CHRAMBACH, A TI DISTINCTION BETWEEN SUPERCOILED AND LINEAR DNA IN TRANSVERSE AGAROSE PORE GRADIENT GEL-ELECTROPHORESIS SO ELECTROPHORESIS LA English DT Article ID SIZE AB Four species of linear DNA and the first four members of a linking series, generated by treatment of plasmid DNA (PUC19, 2.7 kb) with mitochondrial topoisomerase I, were differentiated by transverse agarose pore gradient gel electrophoresis. The experimental curves of migration distance vs. agarose concentration (Ferguson curves) of supercoiled DNA exhibit a steeper trajectory than those of linear DNA of the same size range. As a consequence, the four supercoiled species exhibit an increase in apparent size (relative to linear DNA standards) with increasing agarose concentration. Both the crossing of the Ferguson curves with those of linear standards as well as the apparent size increase with agarose concentration can serve to detect supercoiled plasmid-sized DNA in mixtures with linear DNA. RP WHEELER, D (reprint author), NICHHD,THEORET & PHYS BIOL LAB,BLDG 10,ROOM 6C101,BETHESDA,MD 20892, USA. NR 17 TC 12 Z9 13 U1 0 U2 12 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 JUL PY 1992 VL 13 IS 7 BP 403 EP 406 DI 10.1002/elps.1150130185 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA JH810 UT WOS:A1992JH81000001 PM 1330534 ER PT J AU SCHEFFNER, M MUNGER, K HUIBREGTSE, JM HOWLEY, PM AF SCHEFFNER, M MUNGER, K HUIBREGTSE, JM HOWLEY, PM TI TARGETED DEGRADATION OF THE RETINOBLASTOMA PROTEIN BY HUMAN PAPILLOMAVIRUS-E7 - E6 FUSION PROTEINS SO EMBO JOURNAL LA English DT Article DE HUMAN PAPILLOMAVIRUSES; HPV E6; HPV E7; RETINOBLASTOMA PROTEIN; UBIQUITIN ID RABBIT SHOPE PAPILLOMAVIRUS; ADENOVIRUS E1A PROTEINS; CELLULAR TUMOR-ANTIGEN; LARGE-T; GENE-PRODUCT; CERVICAL-CARCINOMA; TYPE-16 DNA; SV40-TRANSFORMED CELLS; SUSCEPTIBILITY GENE; TRANSFORMED-CELLS AB The E6 and the E7 proteins of the oncogenic human papillomavirus types 16 and 18 can stably associate with p53 and the retinoblastoma protein, respectively. The E6-p53 interaction results in the accelerated degradation of p53 in vitro via the ubiquitin-dependent proteolysis system. In this study we demonstrate that a fusion protein consisting of the N-terminal half of the HPV-16 E7 protein and the full length HPV-16 E6 protein promotes the in vitro degradation of the retinoblastoma protein. This indicates that the property of the HPV-16 E6 protein to stimulate the degradation of p53 can be targeted to other proteins. Unlike the HPV-16 or HPV-18 E6 protein, the E6 proteins of HPV-6 and 11 do not bind to p53 and consequently do not target p53 for degradation. Analogous E7-E6 fusion proteins using the E6 proteins of HPV-6 and HPV-11, however, also have the ability to promote the degradation of the retinoblastoma protein, indicating that the property to target associated proteins for degradation is shared by the anogenital specific HPV E6 proteins. 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 101 Z9 103 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JUL PY 1992 VL 11 IS 7 BP 2425 EP 2431 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JB278 UT WOS:A1992JB27800008 PM 1321031 ER PT J AU THOTAKURA, NR DESAI, RK SZKUDLINSKI, MW WEINTRAUB, BD AF THOTAKURA, NR DESAI, RK SZKUDLINSKI, MW WEINTRAUB, BD TI THE ROLE OF THE OLIGOSACCHARIDE CHAINS OF THYROTROPIN ALPHA-SUBUNIT AND BETA-SUBUNIT IN HORMONE ACTION SO ENDOCRINOLOGY LA English DT Article ID HUMAN CHORIONIC-GONADOTROPIN; ADENYLATE-CYCLASE SYSTEM; LINKED OLIGOSACCHARIDES; CARBOHYDRATE MOIETY; BIOACTIVITY; DEGLYCOSYLATION; GLYCOSYLATION; TRANSDUCTION; SIGNAL AB TSH, a dimeric glycoprotein hormone, has two N-linked complex-type oligosaccharide chains on the alpha-subunit and one on the beta-subunit. The oligosaccharide chains of TSH are important for the expression of hormonal activity, but the contribution of those on each of the subunits to the activity is not clear. In the current study we have determined the relative importance of the oligosaccharide chains of TSH subunits using a recently reported method of enzymatic deglycosylation. The alpha- and beta-subunits of bovine TSH were deglycosylated with endoglycosidase-F and recombined to obtain differentially deglycosylated TSH. The derivatives showed no differences in their receptor-binding activities. The in vitro bioactivity of these derivatives was assessed by measuring adenylyl cyclase activity in bovine thyroid membranes and stimulation of cAMP production and growth in FRTL-5 cells. In the adenylyl cyclase assay, deglycosylation of the alpha-subunit alone had a more profound effect on the activity [maximal stimulatory activity (V(max)), 13% that of alpha,beta) than when the beta-subunit alone was deglycosylated (V(max), 50% that of alpha,beta). In the FRTL-5 assays, removal of carbohydrate from TSH-alpha, but not the beta-subunit, caused a 2- to 3-fold increase in the concentration required for half-maximal stimulation, with minimal change in the apparent V(max). The adenylyl cyclase assay in bovine membranes was more sensitive to carbohydrate removal than the assays of rat FRTL-5 cells, in which the derivatives with lower activity were able to stimulate cAMP and growth to near-maximal levels, albeit at 3-fold higher concentrations. These results indicate that the carbohydrate chains in both subunits of TSH, particularly those in the alpha-subunit, are important in hormone action. In contrast to previous reports, our study shows that the beta-subunit plays a role in signal transduction. RP THOTAKURA, NR (reprint author), NIDDKD, MOLEC CELLULAR & NUTR ENDOCRINOL BRANCH, BLDG 10, ROOM 8D14, BETHESDA, MD 20892 USA. NR 25 TC 30 Z9 30 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 1992 VL 131 IS 1 BP 82 EP 88 DI 10.1210/en.131.1.82 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JC258 UT WOS:A1992JC25800013 PM 1377127 ER PT J AU SHIVER, TM SACKETT, DL KNIPLING, L WOLFF, J AF SHIVER, TM SACKETT, DL KNIPLING, L WOLFF, J TI INTERMEDIATE FILAMENTS AND STEROIDOGENESIS IN ADRENAL Y-1 CELLS - ACRYLAMIDE STIMULATION OF STEROID-PRODUCTION SO ENDOCRINOLOGY LA English DT Article ID MICROTUBULE-ASSOCIATED PROTEINS; TUMOR-CELLS; PTK1 CELLS; ORGANIZATION; VIMENTIN; HORMONE; LIPIDS; CYTOSKELETON; PURIFICATION; CULTURE AB The possible role of intermediate filaments in steroidogenesis was investigated in Y-1 mouse adrenal tumor cells by treatment with acrylamide, which is thought to disrupt intermediate filaments without directly affecting microtubules or microfilaments. Treatment of cells with 5 mm acrylamide increases steroidogenesis after a lag period of 46 h and induces rounding of the cells at approximately the same time. The effect of acrylamide on steroidogenesis is not cAMP mediated and occurs before pregnenolone formation. DNA synthesis is inhibited, while protein synthesis is not. Acrylamide does not affect polymerization/depolymerization of microtubules in vitro. Acrylamide stimulation of steroidogenesis is additive with that produced by either colchicine or ACTH, implying that acrylamide, ACTH, and colchicine act at different rate-limiting steps in steroidogenesis. In addition, acrylamide stimulation is additive with that of forskolin. Pretreatment of cells with taxol, an agent that specifically promotes microtubule polymerization, decreases acrylamide-stimulated (as well as colchicine or ACTH-stimulated) steroidogenesis, implying that there must also be some shared elements in the stimulating pathways. We hypothesize that regulation of steroidogenesis in the Y-1 cell depends on 1) disruption of a vimentin or tubulin coat surrounding lipid droplets and 2) possible functional shortening of the distance between cholesterol droplets and the mitochondrion. However, because of interactions between cytoplasmic fibers, it is currently impossible to say whether interruption of any one of them is a direct or indirect stimulus of steroidogenesis. C1 NIDDKD, BETHESDA, MD 20892 USA. NR 40 TC 29 Z9 29 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 1992 VL 131 IS 1 BP 201 EP 207 DI 10.1210/en.131.1.201 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JC258 UT WOS:A1992JC25800030 PM 1319319 ER PT J AU AMBROZ, C CATT, KJ AF AMBROZ, C CATT, KJ TI ANGIOTENSIN-II RECEPTOR-MEDIATED CALCIUM INFLUX IN BOVINE ADRENAL GLOMERULOSA CELLS SO ENDOCRINOLOGY LA English DT Article ID ALDOSTERONE PRODUCTION; CYTOSOLIC CALCIUM; CHANNEL; POTASSIUM; RAT; CA-2+; ACTIVATION; SECRETION; RESPONSES; PATHWAYS AB The cytoplasmic calcium ([Ca2+]i) response to angiotensin II (AII) in bovine adrenal glomerulosa cells is characterized by an initial transient peak due to intracellular Ca2+ mobilization, followed by a sustained plateau phase that is dependent on Ca2+ entry from the extracellular fluid. In Fura-2 loaded cells, the calcium channel antagonists, nifedipine (1-mu-M) and verapamil (20-mu-M), only partially reduced the cytosolic calcium profile induced by All. The dihydropyridine agonist, Bay K 8644, caused a moderate increase in [Ca2+]i when added in concentrations of 50-100 nm, but did not enhance the AII-induced rise in [Ca2+]i. These results indicate that most of the AII-stimulated Ca2+ influx is through channels that are insensitive to dihydropyridines and verapamil. In contrast, the inorganic Ca2+ channel blocker, LaCl3 (10-mu-M), inhibited the AII-induced plateau phase by more than 50%. The All-induced Ca2+ signal was not affected by treatment with pertussis toxin (100-300 ng/ml for 12 h). The prior addition of specific AII-antagonists (DuP 753, a nonpeptide antagonist, and three peptide analogs, [Sar1,Thr8]AII, [Sar1,Ala8]AII, and [Sar1,Ile8]AII) completely inhibited the AII-induced Ca2+ signal. However, addition of up to 25,000 molar excess of these antagonists at intervals from 10 sec to 5 min after AII caused progressively less attenuation of the sustained Ca2+ signal. After 5 min, addition of antagonists did not inhibit the agonist-induced Ca2+ response for up to 20 min. The progressive loss of ability of the antagonists to inhibit the sustained elevation of [Ca2+]i could reflect prolonged activation of the receptor or of a subsequent process that maintains Ca2+ influx despite receptor blockade. It is possible that sequestration and/or endocytosis of the AII-receptor complex is accompanied by continued generation of intracellular signals that contribute to the maintenance of the [Ca2+]i response. C1 NICHHD, ENDOCRINOL & REPROD BRANCH, ROOM B1-L400, BLDG 10, BETHESDA, MD 20892 USA. FU NICHD NIH HHS [HD-07383-03] NR 43 TC 42 Z9 42 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 1992 VL 131 IS 1 BP 408 EP 414 DI 10.1210/en.131.1.408 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JC258 UT WOS:A1992JC25800061 PM 1377126 ER PT J AU OSTROWSKI, NL LOLAIT, SJ BRADLEY, DJ OCARROLL, AM BROWNSTEIN, MJ YOUNG, WS AF OSTROWSKI, NL LOLAIT, SJ BRADLEY, DJ OCARROLL, AM BROWNSTEIN, MJ YOUNG, WS TI DISTRIBUTION OF V1A-VASOPRESSIN AND V2-VASOPRESSIN RECEPTOR MESSENGER RIBONUCLEIC-ACIDS IN RAT-LIVER, KIDNEY, PITUITARY AND BRAIN SO ENDOCRINOLOGY LA English DT Note ID VASOPRESSIN BINDING-SITES; AUTORADIOGRAPHIC LOCALIZATION; ARGININE VASOPRESSIN; BLOOD-FLOW; ANTAGONIST; V1 AB The hepatic, vascular-type (V1aR) and the renal, antidiuretic-type (V2R) vasopressin receptor cDNAs were recently cloned from rat liver and kidney libraries, respectively. DNA fragments containing the region encoding the putative 5/6 transmembrane loops of these receptors were subcloned, separately, into RNA polymerase promoter-containing vectors from which S-35-labeled sense and antisense riboprobes were synthesized. In situ hybridization histochemistry showed high levels of V1aR transcripts in the liver and the renal medulla among the vascular bundles. Spars- labeling was found in the renal cortex, but there were no grains over the glomeruli. V1aR mRNA was detected in many brain areas, including the hippocampal formation, central amygdala, dorsolateral septum, lateral hypothalamus, suprachiasmatic, ventromedial, dorsomedial, and arcuate nuclei of the hypothalmus, nucleus of the solitary tract, cerebellum, spinal nucleus of the trigeminal tract, reticular formation, inferior olivary nucleus, and choroid plexus. Rare labeled cells were seen along the periphery of the posterior pituitary. V2R transcripts were not detected in the liver or brain, but were present in high amounts in the inner and outer renal medulla, primarily associated with collecting ducts. Sparser labeling was found in the renal cortex, and no grains were seen over the glomeruli. These data confirm the expression of the V1a vasopressin receptor in liver and brain and demonstrate that kidney expresses mRNAs encoding V1a and V2 vasopressin receptors. C1 NIMH, CELL BIOL LAB, BETHESDA, MD 20892 USA. RI Young, W Scott/A-9333-2009; Brownstein, Michael/B-8609-2009 OI Young, W Scott/0000-0001-6614-5112; NR 21 TC 166 Z9 169 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 1992 VL 131 IS 1 BP 533 EP 535 DI 10.1210/en.131.1.533 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JC258 UT WOS:A1992JC25800077 PM 1535312 ER PT J AU MUSHAK, EW PIVER, WT AF MUSHAK, EW PIVER, WT TI AGRICULTURAL CHEMICAL UTILIZATION AND HUMAN HEALTH SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material AB The public is justifiably concerned about the human health effects of agricultural chemicals. The many gaps in information about the mechanisms of toxic action, human exposures, and the nature and extent of human health effects are large. Very few older pesticides, in particular, have been tested for human health effects. Workers who produce, harvest, store, transport, process, and prepare food and fibers are exposed to many chemicals that are potentially hazardous and that are used in agriculture. The occupational health of these workers has not been adequately studied, and protective efforts have sometimes been minimal. Valid and accurate risk assessment is best based on sound information about how chemicals, in this case agricultural chemicals, are involved in toxic events-their mechanisms of action. These health effects include tumor promotion, chronic and acute neurotoxicity, immunotoxicity, and reproductive and developmental toxicity. Another key part of risk assessment is exposure assessment. Fundamental studies of the toxicology of target organisms and nontarget organisms exposed to agricultural chemicals are needed to discover and develop better solutions to the problems of agricultural pest control, including better formulations, optimal application rates and public education in safety and alternative agricultural practices. The large number of pesticides that have never been adequately tested for effects on human health is particularly worrisome in tight of emerging information about delayed nervous system effects. RP MUSHAK, EW (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 7 Z9 7 U1 0 U2 1 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 1992 VL 97 BP 269 EP 274 DI 10.2307/3431363 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA JL411 UT WOS:A1992JL41100040 PM 1396466 ER PT J AU SABLJIC, A PIVER, WT AF SABLJIC, A PIVER, WT TI QUANTITATIVE MODELING OF ENVIRONMENTAL FATE AND IMPACT OF COMMERCIAL CHEMICALS SO ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY LA English DT Article; Proceedings Paper CT SYMP ON STRUCTURE-ACTIVITY AND STRUCTURE-PROPERTY RELATIONSHIPS ( SARS ) IN ENVIRONMENTAL CHEMISTRY AND TOXICOLOGY, PACIFICHEM 89 CY DEC 17-22, 1989 CL HONOLULU, HI SP AMER CHEM SOC, CHEM SOC JAPAN, CANADIAN SOC CHEM DE ACUTE TOXICITY; BIOACCUMULATION; MICROBIAL BIODEGRADATION; QSAR MODELING; SOIL SORPTION ID WATER PARTITION-COEFFICIENTS; POLYCYCLIC AROMATIC-HYDROCARBONS; SOIL SORPTION COEFFICIENTS; MOLECULAR CONNECTIVITY INDEXES; BIOCONCENTRATION FACTORS; TOPOLOGICAL INDEXES; ORGANIC-CHEMICALS; PHYSICOCHEMICAL PROPERTIES; CHLORINATED BENZENES; XENOBIOTIC CHEMICALS AB Present laws in many countries require that all commercial chemicals be assessed for their environmental behavior and hazards. Because there are a large number of chemicals currently in common use (approximately 100,000) and new chemicals are being registered at a very high rate (1,000 per year), it is obvious that our human and material resources are insufficient to obtain experimentally even basic information about environmental fate and effects for all these chemicals. Thus, it is necessary to develop quantitative models that will accurately and rapidly predict environmental behavior for large sets of chemicals. During the last decade, a considerable effort has been made to develop methods that use molecular characteristics to describe environmental behavior of organic pollutants. Thus far, molecular connectivity indexes have been shown to be the most successful structural property for describing and predicting soil sorption coefficients, association coefficients with dissolved humic substances, Henry's law constants, bioconcentration factors in aquatic organisms and vegetation, biodegradation rates, and fish acute toxicity. The general quantitative model, based on the first-order molecular connectivity index (MCI), has been developed for the accurate estimation of soil sorption coefficients for predominantly hydrophobic chemicals: polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), halogenated hydrocarbons, and phenols. It is possible to extend this model for many classes of agricultural chemicals. A similar model, based on the second-order valence MCI, has been developed for fish bioconcentration factors of PCBs, chlorinated diphenyl oxides, halogenated hydrocarbons, PAHs, and phenols, plus substituted benzenes. Furthermore, a prototype expert system has been developed for classifying untested chemicals as readily or not readily biodegradable, based on their chemical structures. Finally, using a standardized data base for fish acute toxicity, we have obtained a simple linear correlation between the valence zero-order MCI and the 96-h LC50 data for a large group of 150 structurally diverse commercial chemicals. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP SABLJIC, A (reprint author), RUDJER BOSKOVIC INST,DEPT PHYS CHEM,POB 1016,YU-41001 ZAGREB,YUGOSLAVIA. RI Sabljic, Aleksandar/D-4146-2011 NR 55 TC 21 Z9 21 U1 0 U2 11 PU SETAC PRESS PI PENSACOLA PA 1010 NORTH 12TH AVE, PENSACOLA, FL 32501-3370 SN 0730-7268 J9 ENVIRON TOXICOL CHEM JI Environ. Toxicol. Chem. PD JUL PY 1992 VL 11 IS 7 BP 961 EP 972 DI 10.1897/1552-8618(1992)11[961:QMOEFA]2.0.CO;2 PG 12 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA JA713 UT WOS:A1992JA71300009 ER PT J AU ALBUS, M ZAHN, TP BREIER, A AF ALBUS, M ZAHN, TP BREIER, A TI ANXIOGENIC PROPERTIES OF YOHIMBINE .1. BEHAVIORAL, PHYSIOLOGICAL AND BIOCHEMICAL MEASURES SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE LA English DT Article DE CORTISOL; ELECTRODERMAL ACTIVITY; HEART RATE; NOREPINEPHRINE; PANIC DISORDER; YOHIMBINE ID PANIC DISORDER; NORADRENERGIC FUNCTION; HEALTHY-SUBJECTS; CARBON-DIOXIDE; ELECTROCHEMICAL DETECTION; ALPRAZOLAM TREATMENT; ANXIETY; ATTACKS; LACTATE; INHALATION AB The anxiogenic effects of yohimbine, a specific alpha-2-receptor antagonist were examined by administering 20 mg yohimbine orally to 8 panic patients on placebo treatment, 7 panic patients on alprazolam treatment and 12 controls using a double-blind randomized design, instructions that minimized the expectancy of experiencing a panic attack and two additional structured situations. Yohimbine induced more pronounced increases in anxiety and panicky ratings, norepinephrine secretion, maximum heart rate and high heart rate variability and decreases in skin temperature in panic patients compared with controls. However, possibly owing to an instructional set and experimental design that distracted patients from unpleasant bodily sensations no panic attacks were observed. C1 NIMH,PSYCHOL & PSYCHOPATHOL LAB,BETHESDA,MD 20892. MARYLAND PSYCHIAT RES CTR,BALTIMORE,MD 21228. RP ALBUS, M (reprint author), MENTAL STATE HOSP,VOCKESTR 72,W-8013 HAAR,GERMANY. NR 54 TC 40 Z9 40 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0940-1334 J9 EUR ARCH PSY CLIN N JI Eur. Arch. Psych. Clin. Neurosci. PD JUL PY 1992 VL 241 IS 6 BP 337 EP 344 DI 10.1007/BF02191958 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA JF215 UT WOS:A1992JF21500003 PM 1504110 ER PT J AU ALBUS, M ZAHN, TP BREIER, A AF ALBUS, M ZAHN, TP BREIER, A TI ANXIOGENIC PROPERTIES OF YOHIMBINE .2. INFLUENCE OF EXPERIMENTAL SET AND SETTING SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE LA English DT Article DE ELECTRODERMAL ACTIVITY; HEART RATE; PANIC DISORDER; STRESS EXPOSURE; YOHIMBINE ID PANIC ATTACKS; HEART-RATE; NORADRENERGIC FUNCTION; EXPERIMENTAL STRESS; BLOOD-PRESSURE; ANXIETY; RESPONSES; HYPERVENTILATION; AGORAPHOBIA; DISORDER AB To study the pharmacological induction of stress along with psychological stress and their possible interaction, 20 mg yohimbine and placebo orally were administered to 8 panic patients on placebo treatment, 7 panic patients on alprazolam treatment and 12 controls in a double-blind crossover design. Two structured situations which can be considered as 'neutral' stressors were included: a mental arithmetic task and a continuous performance task. Mental arithmetic induced robust increases in ratings of panicky, anxiety, nervousness, heart rate and electrodermal activity, while the continuous performance task induced increases exclusively in skin conductance reaction. Patients responded to these tasks less than controls with regard to subjective ratings and electrodermal activity. Yohimbine did not potentiate the response to the tasks in the patients. In controls, heart rate during the mental arithmetic task, but not during rest, was increased after yohimbine. In contrast to other yohimbine challenge studies no panic attacks were observed. It is hypothesized that the experimental design together with an instructional set that reduces expectancy factors and the inclusion of structured and time-limited tasks in a challenge paradigm is able to reduce the anxiogenic effects of yohimbine. C1 NIMH,PSYCHOL & PSYCHOPATHOL LAB,BETHESDA,MD 20892. MARYLAND PSYCHIAT RES CTR,BALTIMORE,MD 21228. RP ALBUS, M (reprint author), MENTAL STATE HOSP HAAR,VOCKESTR 72,W-8013 HAAR,GERMANY. NR 38 TC 14 Z9 14 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0940-1334 J9 EUR ARCH PSY CLIN N JI Eur. Arch. Psych. Clin. Neurosci. PD JUL PY 1992 VL 241 IS 6 BP 345 EP 351 DI 10.1007/BF02191959 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA JF215 UT WOS:A1992JF21500004 PM 1504111 ER PT J AU KROLL, MH CHESLER, R AF KROLL, MH CHESLER, R TI RATIONALE FOR USING MULTIPLE-REGRESSION ANALYSIS WITH COMPLEX INTERFERENCES SO EUROPEAN JOURNAL OF CLINICAL CHEMISTRY AND CLINICAL BIOCHEMISTRY LA English DT Article AB Non-specificities and interferences may become complex when they involve the analyte as well as other interfering substances. These non-specificities and interferences are known as analyte-dependent and multi-interferent interferences. Multiple regression analysis has proven valuable in analysing this type of interference, but the theoretical foundation for using multiple regression analysis to study the basic mechanisms of interference has not been explicitly demonstrated. Graph theory can depict and model the basic mechanisms of interferences and the possible interactions. The relationship between the analyte, the interferents, and the response of the instrument to these entities can be approximated by a polymial of order three, which includes partial derivatives and cross-terms. The partial derivatives relate to the different interactions found with the graph theory model. Further, the partial derivatives can be associated with the coefficients in the multiple regression analysis when the respective values of the three variables (analyte, interferent one, and interferent two) are multiplied by one another. One can decide to retain or discard the coefficient of a variable, based on the statistical significance of the coefficient. The respective interactions in the graphic model can then be assembled and the framework of the interference mechanism established. RP KROLL, MH (reprint author), NIH,CTR CLIN,DEPT CLIN PATHOL,BLDG 10,ROOM 2C-407,BETHESDA,MD 20892, USA. NR 13 TC 10 Z9 10 U1 0 U2 2 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0939-4974 J9 EUR J CLIN CHEM CLIN JI Eur. J. Clin. Chem. Clin. Biochem. PD JUL PY 1992 VL 30 IS 7 BP 415 EP 424 PG 10 WC Biochemistry & Molecular Biology; Medical Laboratory Technology SC Biochemistry & Molecular Biology; Medical Laboratory Technology GA JH812 UT WOS:A1992JH81200006 PM 1525264 ER PT J AU SONCRANT, TT HOLLOWAY, HW HORWITZ, B RAPOPORT, SI LAMOUR, YA AF SONCRANT, TT HOLLOWAY, HW HORWITZ, B RAPOPORT, SI LAMOUR, YA TI EFFECT OF NUCLEUS BASALIS MAGNOCELLULARIS ABLATION ON LOCAL BRAIN GLUCOSE-UTILIZATION IN THE RAT - FUNCTIONAL BRAIN REORGANIZATION SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE NUCLEUS BASALIS MAGNOCELLULARIS; CEREBRAL METABOLISM; CORRELATIONAL ANALYSIS; PLASTICITY; FUNCTIONAL INTERACTION ID ALZHEIMERS-DISEASE; CHOLINE-ACETYLTRANSFERASE; METABOLIC RATES; LESIONS; NEURONS; FOREBRAIN; PATTERN; INTERCORRELATIONS; HYPERTROPHY; DEMENTIA AB After unilateral destruction of the nucleus basalis magnocellularis (NBM) in 3-month-old rats, which reduces cholinergic inputs to the ipsilateral frontoparietal neocortex, regional cerebral metabolic rates for glucose (rCMRglc) of denervated cortex are initially reduced, but nearly normalize by 2 weeks. To examine functional reorganization of the brain after unilateral destruction of the NBM, a correlation analysis of rCMRglc was performed on two groups of 16 young rats 2 weeks after stereotaxic ablation of the right NBM with ibotenate or sham surgery. rCMRglc was measured in 117 brain regions of awake rats with the [C-14]deoxyglucose method. For each region pair, a partial correlation coefficient was calculated for rCMRgic across animals. Most correlations between cholinergic nuclei of both left and right forebrain (medial septum and diagonal band) and right (66/72, mean increase 0.44) but not left (39/72) frontoparietal cortical regions were larger (P < 0.001) in lesioned rats, as were those between most frontoparietal region pairs (516/630, P < 0.001). These results suggest that, after unilateral NBM ablation, (1) functional interactions are established between the remaining cholinergic forebrain and the deafferented cortex, (2) the neocortex becomes more integrated, and (3) functional reorganization involves both cortical hemispheres. These changes do not correspond to those reported to occur in Alzheimer's disease. C1 INSERM,U161,F-75014 PARIS,FRANCE. RP SONCRANT, TT (reprint author), NIA,NEUROSCI LAB,10-6C103,BETHESDA,MD 20892, USA. NR 35 TC 9 Z9 9 U1 2 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JUL 1 PY 1992 VL 4 IS 7 BP 653 EP 662 DI 10.1111/j.1460-9568.1992.tb00174.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA JE466 UT WOS:A1992JE46600007 ER PT J AU WILSON, CA BERKOWITZ, BA HATCHELL, DL AF WILSON, CA BERKOWITZ, BA HATCHELL, DL TI OXYGEN KINETICS IN PRERETINAL PERFLUOROTRIBUTYLAMINE SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE OXYGEN; F-19 NMR; PERFLUOROCARBON PERFLUOROTRIBUTYLAMINE; RETINA; VITREOUS; PRERETINAL SPACE; RABBIT EYE ID F-19 NMR; INVIVO; LIQUIDS; TENSION C1 DUKE UNIV,DEPT OPHTHALMOL,DURHAM,NC 27706. DUKE UNIV,DEPT CELL BIOL,DURHAM,NC 27706. NIEHS,RES TRIANGLE PK,NC 27709. VET ADM MED CTR,DURHAM,NC 27710. FU NEI NIH HHS [R01 EY02903] NR 14 TC 18 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD JUL PY 1992 VL 55 IS 1 BP 119 EP 126 DI 10.1016/0014-4835(92)90099-E PG 8 WC Ophthalmology SC Ophthalmology GA JJ582 UT WOS:A1992JJ58200015 PM 1397120 ER PT J AU KORTE, GE HAGEMAN, GS PRATT, DV GLUSMAN, S MARKO, M OPHIR, A AF KORTE, GE HAGEMAN, GS PRATT, DV GLUSMAN, S MARKO, M OPHIR, A TI CHANGES IN MULLER CELL PLASMA-MEMBRANE SPECIALIZATIONS DURING SUBRETINAL SCAR FORMATION IN THE RABBIT SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE GLIA; GLYCOCONJUGATE; MULLER CELL; PLASMA MEMBRANE; RABBIT; ULTRASTRUCTURE ID RETINAL-DETACHMENT C1 MONTEFIORE MED CTR,ALBERT EINSTEIN COLL MED,DEPT ANAT,BRONX,NY 10467. ST LOUIS UNIV,SCH MED,DEPT OPHTHALMOL,BETHESDA EYE INST,ST LOUIS,MO 63104. OREGON HLTH SCI UNIV,DEPT NEUROL,PORTLAND,OR 97201. NEW YORK STATE DEPT HLTH,WADSWORTH CTR LABS & RES,NIH,ALBANY,NY 12201. HADASSAH UNIV HOSP,DEPT OPHTHALMOL,JERUSALEM,ISRAEL. RP KORTE, GE (reprint author), MONTEFIORE MED CTR,ALBERT EINSTEIN COLL MED,DEPT OPHTHALMOL,111 E 210TH ST,BRONX,NY 10467, USA. FU NCRR NIH HHS [RR011219]; NEI NIH HHS [EY06463, EY08284] NR 18 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD JUL PY 1992 VL 55 IS 1 BP 155 EP 162 DI 10.1016/0014-4835(92)90103-Y PG 8 WC Ophthalmology SC Ophthalmology GA JJ582 UT WOS:A1992JJ58200019 PM 1397123 ER PT J AU MCCLUNG, JK KING, RL WALKER, LS DANNER, DB NUELL, MJ STEWART, CA DELLORCO, RT AF MCCLUNG, JK KING, RL WALKER, LS DANNER, DB NUELL, MJ STEWART, CA DELLORCO, RT TI EXPRESSION OF PROHIBITIN, AN ANTIPROLIFERATIVE PROTEIN SO EXPERIMENTAL GERONTOLOGY LA English DT Article; Proceedings Paper CT CONF ON HUMAN DIPLOID FIBROBLAST-LIKE CELLS AS A MODEL SYSTEM FOR THE STUDY OF SENESCENCE - CURRENT STATUS : 1991 CY DEC 15-18, 1991 CL SAMUEL ROBERTS NOBLE FDN, ARDMORE, OK HO SAMUEL ROBERTS NOBLE FDN DE PROHIBITIN; CELL CYCLE; ANTIPROLIFERATIVE; MESSENGER RNA; SENESCENCE ID HUMAN-DIPLOID FIBROBLASTS; TUMOR SUPPRESSOR GENES; RAT-LIVER; MICROINJECTION SYSTEM; CELLULAR SENESCENCE; MESSENGER-RNA; DNA-SYNTHESIS; CELLS; DIFFERENTIATION; PRODUCT C1 NIA,MOLEC GENET LAB,BALTIMORE,MD 21224. RP MCCLUNG, JK (reprint author), SAMUEL ROBERTS NOBLE FDN INC,DIV BIOMED,CELL BIOL SECT,POB 2180,2510 HIGHWAY 199 E,ARDMORE,OK 73402, USA. NR 26 TC 29 Z9 29 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD JUL-AUG PY 1992 VL 27 IS 4 BP 413 EP 417 DI 10.1016/0531-5565(92)90074-A PG 5 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA JF774 UT WOS:A1992JF77400011 PM 1459218 ER PT J AU THWEATT, R MURANO, S FLEISCHMANN, RD GOLDSTEIN, S AF THWEATT, R MURANO, S FLEISCHMANN, RD GOLDSTEIN, S TI ISOLATION AND CHARACTERIZATION OF GENE-SEQUENCES OVEREXPRESSED IN WERNER SYNDROME FIBROBLASTS DURING PREMATURE REPLICATIVE SENESCENCE SO EXPERIMENTAL GERONTOLOGY LA English DT Article; Proceedings Paper CT CONF ON HUMAN DIPLOID FIBROBLAST-LIKE CELLS AS A MODEL SYSTEM FOR THE STUDY OF SENESCENCE - CURRENT STATUS : 1991 CY DEC 15-18, 1991 CL SAMUEL ROBERTS NOBLE FDN, ARDMORE, OK HO SAMUEL ROBERTS NOBLE FDN DE WERNER SYNDROME; SENESCENT FIBROBLASTS; OVEREXPRESSED GENES ID FACTOR BINDING PROTEIN-3; CULTURED HUMAN-FIBROBLASTS; ALPHA-B-CRYSTALLIN; SKIN FIBROBLASTS; DNA-SYNTHESIS; PROMOTER; CELLS; EXPRESSION; MUSCLE C1 UNIV ARKANSAS MED SCI HOSP,DEPT MED,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT BIOCHEM & MOLEC BIOL,LITTLE ROCK,AR 72205. NCI,CELL BIOL LAB,BETHESDA,MD 20892. JOHN L MCCLELLAN MEM VET ADM MED CTR,GERIATR RES EDUC & CLIN CTR,LITTLE ROCK,AR 72205. FU NIA NIH HHS [AG-08708, AG-05554] NR 30 TC 13 Z9 13 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD JUL-AUG PY 1992 VL 27 IS 4 BP 433 EP 440 DI 10.1016/0531-5565(92)90078-E PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA JF774 UT WOS:A1992JF77400015 PM 1281115 ER PT J AU LOCASCIULLI, A PONTISSO, P RUVOLETTO, MG VANLINT, MT GUALANDI, F HIBBS, JR YOUNG, NS ALBERTI, A BACIGALUPO, A AF LOCASCIULLI, A PONTISSO, P RUVOLETTO, MG VANLINT, MT GUALANDI, F HIBBS, JR YOUNG, NS ALBERTI, A BACIGALUPO, A TI DETECTION OF HEPATITIS-C VIRUS(HCV)RNA IN PATIENTS WITH LIVER-DISEASE AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 OSP S GERARDO,DEPT PEDIAT HEMATOL,MONZA,ITALY. UNIV PADUA,I-35100 PADUA,ITALY. NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. OSP S MARTINO,HEMATOL 2,GENOA,ITALY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 1992 VL 20 IS 6 BP 716 EP 716 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA JA734 UT WOS:A1992JA73400047 ER PT J AU FALK, LA KESSLER, S RUSCETTI, FW LONGO, D KENNY, JJ AF FALK, LA KESSLER, S RUSCETTI, FW LONGO, D KENNY, JJ TI REGULATION OF HUMAN CD34 POSITIVE PROGENITOR-CELL GROWTH AND DIFFERENTIATION BY TRANSFORMING GROWTH FACTOR-B SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 BCDP,PRI,DYNCORP,FREDERICK,MD. NCI,FCRDC,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 1992 VL 20 IS 6 BP 738 EP 738 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA JA734 UT WOS:A1992JA73400134 ER PT J AU ORLIC, D BODINE, DM AF ORLIC, D BODINE, DM TI MURINE LONG-TERM REPOPULATING STEM-CELLS ARE PRESENT IN BOTH LOW-DENSITY AND HIGH-DENSITY ELUTRIATION FRACTIONS SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 1992 VL 20 IS 6 BP 750 EP 750 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA JA734 UT WOS:A1992JA73400177 ER PT J AU CARROLL, MP RAPP, UR MAY, WS AF CARROLL, MP RAPP, UR MAY, WS TI PKC CAN DIRECTLY ACTIVATE A NECESSARY ENZYMATIC COMPONENT OF HEMATOPOIETIC PROLIFERATION, RAF-1 SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV HOSP,CTR ONCOL,BALTIMORE,MD 21205. NCI,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 1992 VL 20 IS 6 BP 752 EP 752 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA JA734 UT WOS:A1992JA73400183 ER PT J AU DUBOIS, CM RUSCETTI, FW ORTIZ, M JACOBSEN, SE KELLER, JR AF DUBOIS, CM RUSCETTI, FW ORTIZ, M JACOBSEN, SE KELLER, JR TI TRANSFORMING GROWTH-FACTOR-BETA (TGF-BETA) IS A POTENT INHIBITOR OF CIS-KIT PROTOONCOGENE PRODUCT IN MURINE PROGENITOR CELLS SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 UNIV SHERBROOKE,FAC MED,SHERBROOKE J1H 5N4,QUEBEC,CANADA. NCI,FCRDC,BRMP,LMI,BETHESDA,MD 20892. NCI,FCRDC,BCDP,PRI,DYNCORP,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 1992 VL 20 IS 6 BP 754 EP 754 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA JA734 UT WOS:A1992JA73400191 ER PT J AU DOUKAS, M CHAVAN, A JACOBSON, S KELLER, J GASS, C BOONE, T HALEY, B AF DOUKAS, M CHAVAN, A JACOBSON, S KELLER, J GASS, C BOONE, T HALEY, B TI MODIFICATION OF THE NUCLEOTIDE BINDING-SITE OF GRANULOCYTE MACROPHAGE-COLONY STIMULATING FACTOR (GM-CSF) DECREASES BIOACTIVITY AND RECEPTOR INTERACTION SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 UNIV KENTUCKY,LUCILLE P MARKEY CANC CTR,LEXINGTON,KY 40506. VET ADM MED CTR,LEXINGTON,KY 40511. NCI,FREDERICK,MD 21701. AMGEN INC,THOUSAND OAKS,CA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 1992 VL 20 IS 6 BP 758 EP 758 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA JA734 UT WOS:A1992JA73400207 ER PT J AU KELLER, JR RUSCETTI, FW JACOBSEN, SEW AF KELLER, JR RUSCETTI, FW JACOBSEN, SEW TI TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) DIRECTLY INHIBITS AND INDIRECTLY ENHANCES HEMATOPOIETIC PROGENITOR-CELL PROLIFERATION - CORRELATION WITH COLONY STIMULATING FACTOR (CSE) RECEPTOR MODULATION SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 DYNCORP INC,PRI,BCDP,FREDERICK,MD 21702. LMI,BRMP,FREDERICK,MD 21702. NCI,FCRDC,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 1992 VL 20 IS 6 BP 760 EP 760 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA JA734 UT WOS:A1992JA73400214 ER PT J AU MACVITTIE, TJ WAISMAN, Y FARESE, AM NATANSON, C PATCHEN, ML SOUZA, LM EICHACKER, PQ AF MACVITTIE, TJ WAISMAN, Y FARESE, AM NATANSON, C PATCHEN, ML SOUZA, LM EICHACKER, PQ TI PROPHYLAXIS IN A CANINE MODEL OF GRAM-NEGATIVE SEPSIS (GNS) USING RECOMBINANT CANINE GRANULOCYTE COLONY-STIMULATING FACTOR (RCG-CSF) SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 AMGEN INC,THOUSAND OAKS,CA. NIH,AFRRI,BETHESDA,MD 20892. NIH,CCMD,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 1992 VL 20 IS 6 BP 771 EP 771 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA JA734 UT WOS:A1992JA73400255 ER PT J AU BROWN, MD VOLJAVEC, AS LOTT, MT MACDONALD, I WALLACE, DC AF BROWN, MD VOLJAVEC, AS LOTT, MT MACDONALD, I WALLACE, DC TI LEBER HEREDITARY OPTIC NEUROPATHY - A MODEL FOR MITOCHONDRIAL NEURODEGENERATIVE DISEASES SO FASEB JOURNAL LA English DT Review DE LEBER HEREDITARY OPTIC NEUROPATHY; MITOCHONDRIAL DNA MUTATIONS; OXIDATIVE PHOSPHORYLATION; GENOTYPE ID GENE ORGANIZATION; DNA MUTATION; NUCLEOTIDE-SEQUENCE; READING FRAMES; GENOME; CONTAINS AB A number of human diseases have been attributed to defects in oxidative pbosphorylation (OXPHOS) resulting from mutations in the mitochondrial DNA (mtDNA). One such disease is Leber's hereditary optic neuropathy (LHON), a neurodegenerative disease of young adults that results in blindness due to atrophy of the optic nerve. The etiology of LHON is genetically heterogeneous and in some cases multifactorial. Eleven mtDNA mutations have been associated with LHON, all of which are missense mutations in the subunit genes for the subunits of the electron transport chain complexes I, III, and IV. Molecular, biochemical, and population genetic studies have categorized these mutations as high risk (class I), low risk (class II), or intermediate risk (class I/II). Class I mutations appear to be primary genetic causes of LHON, while class II mutations are frequently found associated with class I genotypes and may serve as exacerbating genetic factors. Different LHON pedigrees can harbor different combinations of class I, II, or I/II mtDNA mutations, as shown by the complete sequence analysis of the mtDNAs of four LHON probands. The various mtDNA genotypes included an isolated class I mutation, combined class I + II mutations, and combined class I/II + II mutations. The occurrence of such genotypes supports the hypothesis that LHON may result from the additive effects of various genetic and environmental insults to OXPHOS, each of which increases the probability of blindness. C1 EMORY UNIV,SCH MED,DEPT GENET & MOLEC MED,1462 CLIFTON RD,ROOM 403,ATLANTA,GA 30322. NIH,BETHESDA,MD 20892. UNIV OTTAWA,FAC MED,OTTAWA K1H 8M5,ONTARIO,CANADA. FU NIGMS NIH HHS [GM46915]; NINDS NIH HHS [NS09042, NS21328] NR 43 TC 170 Z9 170 U1 1 U2 7 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 JUL PY 1992 VL 6 IS 10 BP 2791 EP 2799 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA JD954 UT WOS:A1992JD95400005 PM 1634041 ER PT J AU HENRICHSEN, J ROBBINS, JB AF HENRICHSEN, J ROBBINS, JB TI PRODUCTION OF MONOVALENT ANTISERA BY INDUCTION OF IMMUNOLOGICAL-TOLERANCE FOR CAPSULAR TYPING OF STREPTOCOCCUS-PNEUMONIAE SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE PNEUMOCOCCAL TYPING; EPITOPE-SPECIFIC IMMUNOLOGICAL TOLERANCE; STREPTOCOCCUS-PNEUMONIAE ID PNEUMOCOCCAL POLYSACCHARIDE; TYPE-6 AB Hyperimmune and high-titered polyclonal pneumococcal antisera, specific for cross-reactive types within groups, were produced in adult rabbits. Purified capsular polysaccharide was injected intravenously into adult rabbits. One week later, these rabbits were given multiple intravenous injections of formalin-inactivated pneumococci of the cross-reactive type by an established method. Each of the resultant antisera were specific for the cross-reactive type indicating that the previous injection of the polysaccharide had induced epitope-specific tolerance. This method was successful for production of antisera against pneumococcal types 6A, 6B, 9N, 9V, 19F and 19A. Polyclonal rabbit pneumococcal antisera have some advantages over murine monoclonal antibodies for serologic studies and this method should be applicable for producing type-specific antibodies to cross-reactive polysaccharides of clinical interest. Further, this method is simpler and generally produces higher titered monovalent (factor) reagents than absorbed antisera. C1 NICHHD,BETHESDA,MD 20892. RP HENRICHSEN, J (reprint author), STATENS SERUM INST,WHO COLLABORATING CTR REFERENCE & RES PNEUMOCOCCI,ARTILLERIVEJ 5,DK-2300 COPENHAGEN,DENMARK. NR 22 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD JUL 1 PY 1992 VL 94 IS 1-2 BP 89 EP 94 PG 6 WC Microbiology SC Microbiology GA JF913 UT WOS:A1992JF91300018 ER PT J AU NELSON, LM AF NELSON, LM TI OVARIAN FAILURE AND G-PROTEINS - DO WE REALLY NEED TO KNOW HOW THEY WORK - REPLY SO FERTILITY AND STERILITY LA English DT Letter RP NELSON, LM (reprint author), NIH,DEPT HLTH & HUMAN SERV,BETHESDA,MD 20892, USA. NR 5 TC 0 Z9 0 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 JUL PY 1992 VL 58 IS 1 BP 218 EP 219 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA JB470 UT WOS:A1992JB47000042 ER PT J AU GEORGE, JD PRICE, CJ MARR, MC KIMMEL, CA SCHWETZ, BA MORRISSEY, RE AF GEORGE, JD PRICE, CJ MARR, MC KIMMEL, CA SCHWETZ, BA MORRISSEY, RE TI THE DEVELOPMENTAL TOXICITY OF ETHYLENE-GLYCOL DIETHYL-ETHER IN MICE AND RABBITS SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID ZERO DOSE CONTROL; DIMETHYL ETHER; RATS; DISPOSITION C1 US EPA,OFF HLTH & ENVIRONM ASSESSMENT,REPROD & DEV TOXICOL BRANCH,WASHINGTON,DC 20460. NIEHS,NATL TOXICOL PROGRAM,DEV & REPROD TOXICOL GRP,RES TRIANGLE PK,NC 27709. RP GEORGE, JD (reprint author), RES TRIANGLE INST,CTR LIFE SCI & TOXICOL,POB 12194,RES TRIANGLE PK,NC 27709, USA. FU NIEHS NIH HHS [N01-ES-55080] NR 37 TC 9 Z9 9 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD JUL PY 1992 VL 19 IS 1 BP 15 EP 25 DI 10.1016/0272-0590(92)90023-B PG 11 WC Toxicology SC Toxicology GA JD216 UT WOS:A1992JD21600003 PM 1397797 ER PT J AU LINDAMOOD, C FARNELL, DR GILES, HD PREJEAN, JD COLLINS, JJ TAKAHASHI, K MARONPOT, RR AF LINDAMOOD, C FARNELL, DR GILES, HD PREJEAN, JD COLLINS, JJ TAKAHASHI, K MARONPOT, RR TI SUBCHRONIC TOXICITY STUDIES OF TERT-BUTYL ALCOHOL IN RATS AND MICE SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID METABOLISM; BUTANOL C1 NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. RP LINDAMOOD, C (reprint author), SO RES INST,KETTERING MEYER LAB,POB 55305,BIRMINGHAM,AL 35255, USA. FU NIEHS NIH HHS [N01-ES-55121] NR 26 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 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD JUL PY 1992 VL 19 IS 1 BP 91 EP 100 DI 10.1016/0272-0590(92)90032-D PG 10 WC Toxicology SC Toxicology GA JD216 UT WOS:A1992JD21600012 PM 1397807 ER PT J AU SABOURIN, PJ MEDINSKY, MA THURMOND, F BIRNBAUM, LS HENDERSON, RF AF SABOURIN, PJ MEDINSKY, MA THURMOND, F BIRNBAUM, LS HENDERSON, RF TI EFFECT OF DOSE ON THE DISPOSITION OF METHOXYETHANOL, ETHOXYETHANOL, AND BUTOXYETHANOL ADMINISTERED DERMALLY TO MALE F344/N RATS SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID ETHYLENE-GLYCOL MONOMETHYL; MONOBUTYL ETHER 2-BUTOXYETHANOL; TESTICULAR TOXICITY; MONOETHYL ETHERS; METABOLISM; ABSORPTION; EXCRETION; EXPOSURE; ALCOHOL; INVITRO C1 LOVELACE BIOMED & ENVIRONM RES INST,INHALAT TOXICOL RES INST,ALBUQUERQUE,NM 87185. NIEHS,RES TRIANGLE PK,NC 27709. FU NIEHS NIH HHS [222-ES-20092] NR 26 TC 27 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 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD JUL PY 1992 VL 19 IS 1 BP 124 EP 132 DI 10.1016/0272-0590(92)90036-H PG 9 WC Toxicology SC Toxicology GA JD216 UT WOS:A1992JD21600016 PM 1397793 ER PT J AU SMITH, GR AF SMITH, GR TI THE EPIDEMIOLOGY AND TREATMENT OF DEPRESSION WHEN IT COEXISTS WITH SOMATOFORM DISORDERS, SOMATIZATION, OR PAIN SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article ID DSM-III; BRIQUETS SYNDROME; ANTI-DEPRESSANTS; DOUBLE-BLIND; SYMPTOMS; ANTIDEPRESSANT; MANAGEMENT; INPATIENTS; ILLNESS; CARE AB This article reviews the relationship between depressive disorders and somatoform disorders, somatization, and pain. These disorders and symptoms are clinically interrelated, yet the nature of the interrelation is not well understood. This review of the literature from 1975 through mid-year 1990 addresses the epidemiology and treatment of these conditions and/or symptoms when they occur together. When robust criteria are used to determine which publications are included, only 14 are available that address depressive disorders, somatoform disorders, and somatization. Similarly, there are only 13 that address depressive disorders and pain. Taken together, these studies indicate that 1) in somatization disorder patients, there is a high prevalence of depression; 2) in patients with major depression, there are substantial levels of hypochondriacal and somatizing symptoms; 3) that depression in the face of coexisting somatization disorder can be successfully treated; 4) in chronic pain patients, there is a high prevalence of depressive disorders; 5) in patients with major depression, pain is a frequent complaint; 6) and finally, that pan improves with the treatment of depression. What is most striking from this review, however, is the very limited number of studies that address these important problems. This lack of research-based data calls for new aggressive research efforts in this area. C1 UNIV ARKANSAS MED SCI HOSP,DEPT PSYCHIAT,NIMH,CTR RURAL MENTAL HLTH CARE RES,LITTLE ROCK,AR 72205. RP SMITH, GR (reprint author), UNIV ARKANSAS MED SCI HOSP,DEPT PSYCHIAT,VA HSR & D FIELD PROGRAM MENTAL HLTH,SLOT 554,LITTLE ROCK,AR 72205, USA. NR 36 TC 87 Z9 98 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JUL PY 1992 VL 14 IS 4 BP 265 EP 272 DI 10.1016/0163-8343(92)90097-T PG 8 WC Psychiatry SC Psychiatry GA HY763 UT WOS:A1992HY76300007 PM 1505748 ER PT J AU MASTRANGELO, MF WEINSTOCK, KG SHAFER, BK HEDGE, AM GARFINKEL, DJ STRATHERN, JN AF MASTRANGELO, MF WEINSTOCK, KG SHAFER, BK HEDGE, AM GARFINKEL, DJ STRATHERN, JN TI DISRUPTION OF A SILENCER DOMAIN BY A RETROTRANSPOSON SO GENETICS LA English DT Article ID MATING-TYPE INFORMATION; SACCHAROMYCES-CEREVISIAE; CELL TYPE; YEAST; GENES; LOCUS; EXPRESSION; MUTANTS; IDENTIFICATION; TRANSCRIPTION AB A galactose-inducible Ty element carrying the HIS3 gene has been used as an insertional mutagen to generate alpha-factor resistant mutants. This collection of Ty-induced mutations includes insertions into the gene for the alpha-factor receptor (STE2), several nonspecific STE genes, and mutations that lead to the expression of the normally silent HML-alpha locus. The hml-alpha "on" mutations fall into two classes, those that disrupt trans-acting regulators involved in silencing HML-alpha and a novel class of mutations that activate HML-alpha by insertion at that locus. The hml-alpha::Ty "on" mutations illustrate the unusual ability of these retrotransposons to activate genes by overcoming gene silencing mechanisms. The hml-alpha::Ty "on" mutations include examples of multimeric Ty arrays. Single Ty and solo delta-insertion derivatives of these Ty multimers restore the ability of the silencing mechanism to repress HML-alpha. C1 NCI,FREDERICK CANC RES & DEV CTR,EUKARYOT GENE EXPRESS LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 47 TC 12 Z9 12 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD JUL PY 1992 VL 131 IS 3 BP 519 EP 529 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA HZ815 UT WOS:A1992HZ81500002 PM 1321064 ER PT J AU CLAUSTRES, M GERRARD, B WHITE, MB DESGEORGES, M KJELLBERG, P ROLLIN, B DEAN, M AF CLAUSTRES, M GERRARD, B WHITE, MB DESGEORGES, M KJELLBERG, P ROLLIN, B DEAN, M TI A NEW MUTATION (1078DELT) IN EXON-7 OF THE CFTR GENE IN A SOUTHERN FRENCH ADULT WITH CYSTIC-FIBROSIS SO GENOMICS LA English DT Note C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. DYN CORP,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RP CLAUSTRES, M (reprint author), CNRS,UPR 8402,INSERM,U249,INST BIOL,BLVD HENRI IV,F-34060 MONTPELLIER,FRANCE. RI LABO, U827/A-8632-2008; Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 8 TC 24 Z9 24 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUL PY 1992 VL 13 IS 3 BP 907 EP 908 DI 10.1016/0888-7543(92)90187-W PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA HY388 UT WOS:A1992HY38800072 PM 1379211 ER PT J AU BUTLER, RN FINKEL, SI LEWIS, MI SHERMAN, FT SUNDERLAND, T AF BUTLER, RN FINKEL, SI LEWIS, MI SHERMAN, FT SUNDERLAND, T TI AGING AND MENTAL-HEALTH - PREVENTION OF CAREGIVER OVERLOAD, ABUSE, AND NEGLECT - A ROUND-TABLE DISCUSSION .3. SO GERIATRICS LA English DT Discussion AB This final installment of a three-part panel discussion on aging and mental health reviews the role of the primary care physician in issues of caregiver burden, elder abuse, and nursing home placement. Federal regulations and reimbursement policies have some effect on how the physician manages these concerns. A teamwork approach to geriatric case management that includes other health professionals is also discussed. C1 NORTHWESTERN UNIV,SCH MED,CHICAGO,IL 60611. NW MEM HOSP,GEROPSYCHIAT SERV,CHICAGO,IL 60611. CUNY MT SINAI SCH MED,DEPT COMMUNITY MED,DIV SOCIAL WORK,NEW YORK,NY 10029. NIMH,GERIATR PSYCHOPHARMACOL UNIT,CHEVY CHASE,MD. RP BUTLER, RN (reprint author), CUNY MT SINAI SCH MED,DEPT GERIATR & ADULT DEV,NEW YORK,NY 10029, USA. NR 7 TC 0 Z9 0 U1 0 U2 1 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 SN 0016-867X J9 GERIATRICS JI Geriatrics PD JUL PY 1992 VL 47 IS 7 BP 53 EP 58 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA JD564 UT WOS:A1992JD56400005 PM 1427113 ER PT J AU MAYS, D GUILMETTE, RA AF MAYS, D GUILMETTE, RA TI TOTAL-BODY EVALUATION OF A THOROTRAST PATIENT - PREFACE SO HEALTH PHYSICS LA English DT Editorial Material C1 NCI, ROCKVILLE, MD 20852 USA. RP MAYS, D (reprint author), INHALAT TOXICOL RES INST, ALBUQUERQUE, NM 87185 USA. NR 1 TC 1 Z9 1 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 JUL PY 1992 VL 63 IS 1 BP 1 EP 2 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 HZ669 UT WOS:A1992HZ66900001 ER PT J AU TRAVIS, LB KATHREN, RL MAYS, D MAYS, CW AF TRAVIS, LB KATHREN, RL MAYS, D MAYS, CW TI COMPREHENSIVE EVALUATION OF A THOROTRAST PATIENT - AN OVERVIEW SO HEALTH PHYSICS LA English DT Article DE THOROTRAST; HUMAN ORGANS; RADIATION, MEDICAL; RADIATION EFFECTS AB For several decades, thousands of people received Thorotrast during the course of angiography and other radiologic procedures. Eventually, as the hazards of this radioactive, radiographic contrast agent became apparent, research was initiated to further evaluate its associated adverse effects. In 1988 and 1989, Charles W. Mays, together with colleagues at a variety of sites, developed a detailed protocol for the comprehensive postmortem evaluation of one subject who had been administered Thorotrast 36 y previously. This case represents the first holistic approach to the analysis of Thorotrast in a whole body, simultaneously assembling clinical and autopsy findings with dosimetric, radiochemical, autoradiographic, and molecular evaluations. C1 WASHINGTON STATE UNIV, CTR HLTH RES & EDUC, US TRANSURANIUM & URANIUM REGISTRIES, RICHLAND, WA 99352 USA. NCI, RADIAT EPIDEMIOL BRANCH, ROCKVILLE, MD 20852 USA. RP TRAVIS, LB (reprint author), NCI, EPIDEMIOL & BIOSTAT PROGRAM, EPN 408, 6130 EXECUT BLVD, ROCKVILLE, MD 20852 USA. RI WSU, USTUR/I-1056-2013 NR 7 TC 2 Z9 2 U1 0 U2 1 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 JUL PY 1992 VL 63 IS 1 BP 10 EP 12 DI 10.1097/00004032-199207000-00001 PG 3 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 HZ669 UT WOS:A1992HZ66900003 PM 1522002 ER PT J AU MAYS, CW AAMODT, RL INN, KGW BROWN, DR GREENBERG, RR IYENGAR, VG SCHIMA, FJ SLABACK, LS TRACY, JW LYNCH, TP MOSSMAN, KL AF MAYS, CW AAMODT, RL INN, KGW BROWN, DR GREENBERG, RR IYENGAR, VG SCHIMA, FJ SLABACK, LS TRACY, JW LYNCH, TP MOSSMAN, KL TI EXTERNAL GAMMA-RAY COUNTING OF SELECTED TISSUES FROM A THOROTRAST PATIENT SO HEALTH PHYSICS LA English DT Article DE THOROTRAST; TH-232; TISSUE SAMPLING; DOSE, INTERNAL AB Results of gamma-ray measurements of selected tissues from a patient who was injected with Thorotrast almost 36 y ago are reported. The purposes of this study were: 1) to determine the relative tissue distribution and activities of specific radionuclides in the Th-232 decay chain, specifically Ra-228 (as measured by Ac-228), Pb-212, and Ra-224 (measured directly and as measured by Pb-212), and 2) to evaluate the level of radioactive disequilibrium among the daughter products. The spleen and liver had the highest concentrations of radioactivity. Bone also appears to be a long-term sink for Th-232 daughter products based on estimates from a small portion of one rib. Larynx and esophagus contained measurable activity, which may have been due to their proximity to the "Thorotrastoma." Radioactivity in the remaining measured tissues were low, as expected. Secular equilibrium could be demonstrated in bone, pancreas, larynx, esophagus, and breast. Significant disequilibrium was observed for spleen, liver, kidney, and red blood cells. Radioactivity measurements reported here will be useful in estimating radiation doses to selected tissues. Such dose estimates are valuable in refining current risk estimates (e.g., liver) and in identifying tissues at risk for further epidemiologic studies. These results, while consistent with other published studies, should be interpreted with caution since measurements were made on only one patient. C1 NATL INST STAND & TECHNOL, GAITHERSBURG, MD 20899 USA. GEORGETOWN UNIV, DEPT RADIAT SCI, WASHINGTON, DC 20007 USA. PACIFIC NW LAB, RICHLAND, WA 99352 USA. RP MAYS, CW (reprint author), NCI, ROCKVILLE, MD 20892 USA. RI WSU, USTUR/I-1056-2013 NR 14 TC 9 Z9 9 U1 0 U2 1 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 JUL PY 1992 VL 63 IS 1 BP 33 EP 40 DI 10.1097/00004032-199207000-00005 PG 8 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 HZ669 UT WOS:A1992HZ66900007 PM 1522008 ER PT J AU PRIEST, ND HUMPHREYS, JAH KATHREN, RL MAYS, CW AF PRIEST, ND HUMPHREYS, JAH KATHREN, RL MAYS, CW TI THE DISTRIBUTION OF THOROTRAST IN HUMAN BONE-MARROW - A CASE-REPORT SO HEALTH PHYSICS LA English DT Article DE THOROTRAST; BONE MARROW; BONES, HUMAN; THORIUM AB Samples of bone containing cellular and fatty bone marrow were removed at autopsy from the body of a woman who, following an automobile accident, had been injected with approximately 25 mL of the radiographic contrast medium Thorotrast. The woman survived for 36 y after the accident and died at age 72 y following bone marrow failure. The samples were analyzed to determine their thorium content by x-ray fluorescence and by image analysis. In addition, Thorotrast was visualized in the different bones examined by light microscopy and by backscattered electron imaging with a scanning electron microscope. The results showed Thorotrast to be largely restricted to areas of cellular bone marrow. In such regions, Thorotrast was present throughout the marrow tissue and was also concentrated within cells that were commonly aggregated within focalized areas of the marrow. Overall the results suggest a rather uniform pattern of Thorotrast uptake by the red bone marrow at different skeletal sites. Significant deposits of Thorotrast were not found in fatty yellow marrow. We conclude that Thorotrast-derived risk estimates for human leukemia following high LET, alpha irradiation may be used for calculating the risks of alpha exposure, but with caution. C1 WASHINGTON STATE UNIV, CTR HLTH RES & EDUC, US TRANSURANIUM & URANIUM REGISTRIES, RICHLAND, WA 99352 USA. NCI, RADIAT EPIDEMIOL BRANCH, BETHESDA, MD 20892 USA. RP PRIEST, ND (reprint author), UKAEA, HARWELL BIOMED RES, BLDG 551, HARWELL LAB, HARWELL OX11 0RA, BERKS, ENGLAND. RI WSU, USTUR/I-1056-2013 NR 20 TC 7 Z9 7 U1 0 U2 2 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 JUL PY 1992 VL 63 IS 1 BP 46 EP 53 DI 10.1097/00004032-199207000-00007 PG 8 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 HZ669 UT WOS:A1992HZ66900009 PM 1522010 ER PT J AU TRAVIS, LB KATHREN, RL BOICE, JD AF TRAVIS, LB KATHREN, RL BOICE, JD TI CANCER RISK FOLLOWING EXPOSURE TO THOROTRAST - OVERVIEW IN RELATION TO A CASE-REPORT SO HEALTH PHYSICS LA English DT Article DE THOROTRAST; RADIATION, MEDICAL; HUMAN ORGANS; EPIDEMIOLOGY AB Radioactive measurements and histopathologic findings are described in a patient administered Thorotrast, a radiographic contrast agent, 36 y prior to death and compared with cancer risks noted in epidemiologic studies. This person [designated as U.S. Uranium Registry (USUR) Case 1001] had prearranged for donation of her body to the USUR and the National Cancer Institute for study. Elevated levels of radioactivity were noted in those organs in which excess cancers have been reported in epidemiologic surveys of Thorotrast-exposed subjects. Hepatic tissue in USUR Case 1001 was estimated to have received an average lifetime absorbed dose of 16.2 Gy, based on radiochemical analyses, consistent with the high risks for liver tumors reported in all studied populations. Thorotrast was present throughout the bone marrow of USUR Case 1001, who died secondary to complications of refractory anemia with excess blasts (RAEB). Elevated risks for acute myeloid leukemia have been noted in Thorotrast patients, and more recently, cases of RAEB and RAEB in transformation have been reported. The thorium decay series includes the bone-seeking radionuclides Ra-224 and Ra-228, which have been associated with high risks for osteosarcomas, although the association between Thorotrast and bone cancer is not as convincing. The skeleton of USUR Case 1001, however, contained significant levels of radioactivity. Other tissues evaluated in USUR Case 1001 included lung, eye, kidney, and breast, which did not contain elevated levels of radioactivity. C1 WASHINGTON STATE UNIV, CTR HLTH RES & EDUC, US TRANSURANIUM & URANIUM REGISTRIES, RICHLAND, WA 99352 USA. RP TRAVIS, LB (reprint author), NCI, RADIAT EPIDEMIOL BRANCH, EXECUT PLAZA N, ROOM 408, 6130 EXECUT BLVD, ROCKVILLE, MD 20852 USA. RI WSU, USTUR/I-1056-2013 NR 44 TC 6 Z9 6 U1 0 U2 2 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 JUL PY 1992 VL 63 IS 1 BP 89 EP 97 DI 10.1097/00004032-199207000-00010 PG 9 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 HZ669 UT WOS:A1992HZ66900012 PM 1522013 ER PT J AU BOICE, J TRAVIS, L SCHIMA, F MOSSMAN, K GOLDMAN, M MCINROY, J KATHREN, R HUBERMAN, E COTELINGAM, J TAUBER, W PRIEST, N PRICE, V GRAHAM, S AF BOICE, J TRAVIS, L SCHIMA, F MOSSMAN, K GOLDMAN, M MCINROY, J KATHREN, R HUBERMAN, E COTELINGAM, J TAUBER, W PRIEST, N PRICE, V GRAHAM, S TI TOTAL-BODY EVALUATION OF A THOROTRAST PATIENT - RECOMMENDATIONS FOR FURTHER-STUDIES SO HEALTH PHYSICS LA English DT Discussion ID CLASSIFICATION C1 LOS ALAMOS NATL LAB, LOS ALAMOS, NM 87544 USA. HARVARD UNIV, SCH PUBL HLTH, BOSTON, MA 02115 USA. GEORGETOWN UNIV, WASHINGTON, DC 20057 USA. ARGONNE NATL LAB, DIV BIOL, ARGONNE, IL 60439 USA. US TRANSURANIUM & URANIUM REGISTRIES, RICHLAND, WA USA. NATL INST STAND & TECHNOL, GAITHERSBURG, MD USA. UKAEA, HARWELL BIOMED RES, HARWELL LAB, HARWELL OX11 0RA, BERKS, ENGLAND. NATL NAVAL MED CTR, DEPT PATHOL, BETHESDA, MD USA. NATL NAVAL MED CTR, DEPT INFECT DIS, BETHESDA, MD USA. NATL NAVAL MED CTR, DEPT HEMATOPATHOL, BETHESDA, MD USA. RP BOICE, J (reprint author), NCI, RADIAT EPIDEMIOL BRANCH, BETHESDA, MD 20892 USA. RI WSU, USTUR/I-1056-2013 NR 2 TC 0 Z9 0 U1 0 U2 3 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 JUL PY 1992 VL 63 IS 1 BP 98 EP 100 PG 3 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 HZ669 UT WOS:A1992HZ66900013 ER PT J AU GIUSTINA, A GIRELLI, A LICINI, M SCHETTINO, M NEGROVILAR, A AF GIUSTINA, A GIRELLI, A LICINI, M SCHETTINO, M NEGROVILAR, A TI THYROTROPIN AND PROLACTIN SECRETION ARE NOT AFFECTED BY PORCINE AND RAT GALANIN IN NORMAL SUBJECTS SO HORMONE AND METABOLIC RESEARCH LA English DT Note ID MECHANISMS; RELEASE C1 UNIV BRESCIA,CATTEDRA CLIN MED,BRESCIA,ITALY. NIEH,RES TRIANGLE PK,NC. NR 10 TC 10 Z9 10 U1 0 U2 0 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD JUL PY 1992 VL 24 IS 7 BP 351 EP 352 DI 10.1055/s-2007-1003333 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JE231 UT WOS:A1992JE23100015 PM 1381331 ER PT J AU DAY, CE ZHAO, TM ROBINSON, MA AF DAY, CE ZHAO, TM ROBINSON, MA TI SILENT ALLELIC VARIANTS OF A T-CELL RECEPTOR V-BETA-12 GENE ARE PRESENT IN DIVERSE HUMAN-POPULATIONS SO HUMAN IMMUNOLOGY LA English DT Article ID VARIABLE REGION GENES; BETA-CHAIN; ANTIGEN RECEPTOR; HUMAN FAMILIES; DNA; POLYMORPHISMS; POLYMERASE; MUTATIONS; SEQUENCE; COMPLEX AB Amino acid substitutions in variable regions of the T-cell receptor (TCR) can alter T-cell reactivity; however, relatively little is known about the extent of allelic variation in human TCR coding sequences. In the present studies, coding region variation in the human TCR Vbeta12.2 gene was examined in detail. Virtually the entire Vbeta12.2 coding region was screened for nucleotide substitutions by single-stranded conformational polymorphism analysis. Four alleles were identified in a sample population of 90 unrelated people from diverse genetic backgrounds. Three of the alleles were common, with estimated frequencies of 0.32, 0.47, and 0.20. Sequence analyses revealed that variation between the alleles was confined to three single-base differences in codons 24, 31, and 45; none of these changes altered the amino acid sequence. No evidence for other coding region differences in this gene were found. This analysis suggests that coding region variation in Vbeta12.2 is limited, and amino acid sequence is highly conserved. RP DAY, CE (reprint author), NIAID,IMMUNOGENET LAB,TWINBROOK FACIL 2,12441 PKLAWN DR,BETHESDA,MD 20892, USA. NR 34 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD JUL PY 1992 VL 34 IS 3 BP 196 EP 202 DI 10.1016/0198-8859(92)90112-Z PG 7 WC Immunology SC Immunology GA JR689 UT WOS:A1992JR68900006 PM 1429043 ER PT J AU HENSON, DE AF HENSON, DE TI ON LUMPING AND SPLITTING SO HUMAN PATHOLOGY LA English DT Editorial Material RP HENSON, DE (reprint author), NCI,BETHESDA,MD 20892, USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD JUL PY 1992 VL 23 IS 7 BP 717 EP 718 DI 10.1016/0046-8177(92)90337-3 PG 2 WC Pathology SC Pathology GA JD203 UT WOS:A1992JD20300001 PM 1612571 ER PT J AU LUFF, RD AF LUFF, RD TI THE BETHESDA SYSTEM FOR REPORTING CERVICAL VAGINAL CYTOLOGIC DIAGNOSES - REPORT OF THE 1991 BETHESDA WORKSHOP SO HUMAN PATHOLOGY LA English DT Article DE BETHESDA SYSTEM; CERVICAL CYTOLOGY; VAGINAL CYTOLOGY; GYNECOLOGIC NOMENCLATURE; PAPANICOLAOU SMEAR RP LUFF, RD (reprint author), NCI,BLDG 10,ROOM 2A33,BETHESDA,MD 20892, USA. NR 5 TC 39 Z9 41 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD JUL PY 1992 VL 23 IS 7 BP 719 EP 721 DI 10.1016/0046-8177(92)90338-4 PG 3 WC Pathology SC Pathology GA JD203 UT WOS:A1992JD20300002 PM 1612572 ER PT J AU ABASSI, ZA TATE, JE GOLOMB, E KEISER, HR AF ABASSI, ZA TATE, JE GOLOMB, E KEISER, HR TI ROLE OF NEUTRAL ENDOPEPTIDASE IN THE METABOLISM OF ENDOTHELIN SO HYPERTENSION LA English DT Article DE ENDOTHELIN; METABOLISM; PEPTIDE PEPTIDOHYDROLASES; PROTEASE INHIBITORS ID BINDING-SITES; CELLS; ENKEPHALINASE; PEPTIDE AB Endothelin is a potent vasoconstrictor produced by endothelial cells. Although endothelin has been studied extensively, little is known about its metabolism in vivo. Neutral endopeptidase EC.3.4.24.11 is reported to degrade endothelin in vitro. Therefore, we studied the effect of neutral endopeptidase inhibition by SQ29,072 on plasma levels and urinary excretion of endogenous and exogenous endothelin. Injection of 30 or 60 mg/kg SQ29,072 into anesthetized rats increased the urinary excretion of endothelin nearly 14-fold. The response was maximal during the first 30 minutes of collection and lasted for 90 minutes. The larger dose of inhibitor caused a 37-43% increase (p less-than-or-equal-to 0.05) in the plasma concentration of endothelin. Only 0.20+/-0.04% of the total radioactivity injected as I-125-endothelin (1-mu-Ci; 1,308 pg) into normal rats was recovered in the urine within 30 minutes. Urinary radioactivity increased to 0.54-0.63% (p less-than-or-equal-to 0.05) of the total infused in rats pretreated with SQ29,072. Chromatographic analysis of radioactivity in the urine revealed that intact endothelin accounted for only 6-9% of the total counts in control rats but 50-56% in rats pretreated with the inhibitor. We also studied the effects of another inhibitor of neutral endopeptidase, SQ28,063, on the distribution of radioactivity in the urine, kidney, and lung of rats injected with I-125-endothelin. SQ28,063 increased urinary excretion of labeled endothelin and increased total radioactivity accumulated in the lung and kidney from 157 and 105 pg to 234 and 157 pg, respectively. Intact endothelin accounted for 90% or more of the accumulated counts in both tissues. These results indicate that 1) little circulating endothelin is cleared into the urine, 2) endothelin in the urine is likely of renal origin, and 3) neutral endopeptidase EC.3.4.24.11 plays a major role in the inactivation of endothelin. RP ABASSI, ZA (reprint author), NHLBI,HYPERTENS ENDOCRINE BRANCH,BLDG 10,ROOM 8C103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 22 TC 149 Z9 152 U1 1 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUL PY 1992 VL 20 IS 1 BP 89 EP 95 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JB928 UT WOS:A1992JB92800015 PM 1618556 ER PT J AU COSTA, JJ KEFFER, JM GOFF, JP METCALFE, DD AF COSTA, JJ KEFFER, JM GOFF, JP METCALFE, DD TI APHIDICOLIN-INDUCED PROLIFERATIVE ARREST OF MURINE MAST-CELLS - MORPHOLOGICAL AND BIOCHEMICAL-CHANGES ARE NOT ACCOMPANIED BY ALTERATIONS IN CYTOKINE GENE INDUCTION SO IMMUNOLOGY LA English DT Article ID DNA POLYMERASE-ALPHA; C-MYC; DIHYDROFOLATE-REDUCTASE; RIBONUCLEIC-ACID; EXPRESSION; FIBROBLASTS; GROWTH; CYCLE; DIFFERENTIATION; LYMPHOCYTES AB Investigations of mast cell biology have often used immortalized cultured cells which are continuously proliferating. In vivo, however, only 2% or fewer tissue mast cells are actively dividing. We used aphidicolin, an inhibitor of DNA polymerase to induce a proliferative arrest of murine mast cells characterized by an inhibition of cell division and thymidine incorporation, with accumulation of cells in G1 and early S phase of the cell cycle. Uridine incorporation and cell viability were not significantly impaired. DNA synthesis and cell division both resumed rapidly upon removal of the drug. Morphometric analysis demonstrated that cell size, granule size, and number of granules per cell were all increased in aphidicolin-treated cells. Proliferative arrest also produced a 14-fold increase in cellular histamine content, but did not alter the proteoglycans synthesized by the cell. The level of c-myc mRNA was reduced in aphidicolin-arrested cells, but returned to the level observed in untreated cells within 1 hr of removal of the drug. In contrast, the constitutive steady-state RNA levels of tumour necrosis factor-alpha (TNF-alpha), B2-microglobulin, actin, and the c-Ha-ras and c-fes proto-oncogenes were not altered. Aphidicolin-induced proliferative arrest did not prevent the induction of TNF-alpha, interleukin-6 (IL-6) and c-fos genes in reponse to calcium ionophore. Both the magnitude and induction kinetics of these messages were similar in aphidicolin-treated and untreated cells. We conclude that proliferative arrest results in morphological and biochemical changes suggestive of cellular maturation, but inhibition of cell division alone is not sufficient to alter mast cell phenotype. Although optimal c-myc expression appears to require active proliferation, cytokine gene induction can occur in non-dividing cells. These data suggest that the proliferative quiescence of in vivo mast cells should not preclude their involvement in biological events via elaboration of multi-functional cytokines. C1 NIAID,MAST CELL PHYSIOL SECT,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DIV MOLEC VIROL & IMMUNOL,ROCKVILLE,MD. NR 39 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD JUL PY 1992 VL 76 IS 3 BP 413 EP 421 PG 9 WC Immunology SC Immunology GA JD876 UT WOS:A1992JD87600012 PM 1382041 ER PT J AU SCHMITZ, JL SCHELL, RF CALLISTER, SM LOVRICH, SD DAY, SP COE, JE AF SCHMITZ, JL SCHELL, RF CALLISTER, SM LOVRICH, SD DAY, SP COE, JE TI IMMUNOGLOBULIN G2 CONFERS PROTECTION AGAINST BORRELIA-BURGDORFERI INFECTION IN LSH HAMSTERS SO INFECTION AND IMMUNITY LA English DT Article ID LYME-DISEASE SPIROCHETE; PASSIVE-IMMUNIZATION; ARTHRITIS; MICE; COMPLEMENT; INDUCTION; PROTEINS; OSPA AB We showed that immune serum and its immunoglobulin fractions, specifically immunoglobulin G2 (IgG2), could confer complete protection to irradiated hamsters challenged with the Lyme disease spirochete. Immune serum and its immunoglobulin fractions also killed Borrelia burgdorferi in vitro. Depletion of complement in vivo abrogated the ability of IgG2 to confer complete protection against B. burgdorferi. Furthermore, the majority of antibody reactivity directed against B. burgdorferi was found in the IgG2 fraction. These findings demonstrate that IgG2 plays an important role in acquired resistance against infection with B. burgdorferi. Additional studies are needed to determine the mechanism(s) by which B. burgdorferi evades host defenses despite the development of an effective borreliacidal antibody response. C1 UNIV WISCONSIN,WISCONSIN STATE LAB,MADISON,WI 53706. GUNDERSON MED FDN,LA CROSSE,WI 54601. NIH,ROCKY MT LABS,HAMILTON,MT 59840. UNIV WISCONSIN,DEPT MED MICROBIOL & IMMUNOL,MADISON,WI 53706. UNIV WISCONSIN,DEPT BACTERIOL,MADISON,WI 53706. UNIV WISCONSIN,DEPT PREVENT MED,MADISON,WI 53706. FU NIAID NIH HHS [AI-22199] NR 29 TC 14 Z9 14 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 JUL PY 1992 VL 60 IS 7 BP 2677 EP 2682 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA JB247 UT WOS:A1992JB24700018 PM 1612738 ER PT J AU BAKER, PJ HRABA, T TAYLOR, CE MYERS, KR TAKAYAMA, K QURESHI, N STUETZ, P KUSUMOTO, S HASEGAWA, A AF BAKER, PJ HRABA, T TAYLOR, CE MYERS, KR TAKAYAMA, K QURESHI, N STUETZ, P KUSUMOTO, S HASEGAWA, A TI STRUCTURAL FEATURES THAT INFLUENCE THE ABILITY OF LIPID-A AND ITS ANALOGS TO ABOLISH EXPRESSION OF SUPPRESSOR T-CELL ACTIVITY SO INFECTION AND IMMUNITY LA English DT Article ID III PNEUMOCOCCAL POLYSACCHARIDE; ANTIBODY-PRODUCING CELLS; RHODOPSEUDOMONAS-SPHAEROIDES; NONTOXIC LIPOPOLYSACCHARIDE; MICE; INACTIVATION; REQUIREMENTS; LYMPHOCYTES; MACROPHAGES; MAGNITUDE AB Lipid A preparations derived from the lipopolysaccharides of several gram-negative bacteria, as well as chemically defined synthetic lipid A's and their analogs (both glucosamine mono- and disaccharides), were used to establish the chemical structures required for (i) abolishing the expression of suppressor T cell (Ts) function and (ii) inducing polyclonal activation of B cells. Salmonella minnesota R595 lipid A (diphosphoryl lipid A) possesses both of these activities. Decreasing the number of phosphate groups in lipid A from two to one (monophosphoryl lipid A) as well as decreasing the fatty acyl content, primarily by removing the residue at the 3 position, resulted in a progressive reduction in toxicity; however, these structural modifications did not influence its ability to abolish the expression of Ts function. Reducing the fatty acyl content from five to four (lipid A precursor IV(A) or I(a)) eliminated the capacity to influence Ts function but not to induce polyclonal activation of B cells. None of the monosaccharide analogs of lipid A examined influenced the expression of Ts activity, although some were able to activate B cells polyclonally. Thus, in order to be able to abolish the expression of Ts function, lipid A (i) must be a glucosamine disaccharide, (ii) may have either one or two phosphate groups, and (iii) must have at least five fatty acyl groups. Also, the chain length of the nonhydroxylated fatty acid, as well as the location of acyloxyacyl groups (2' versus 3' position), may play an important role. These findings indicate that the chemical structures responsible for the toxicity of lipid A differ from those that influence its capacity to abolish the expression of Ts function and to induce polyclonal activation of B cells. C1 RIBI IMMUNOCHEM RES INC,HAMILTON,MT 59840. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MYCOBACTERIOL RES LAB,MADISON,WI 53705. GIFU UNIV,DEPT APPL BIOORGAN CHEM,GIFU 50111,JAPAN. SANDOZ GMBH,A-1235 VIENNA,AUSTRIA. OSAKA UNIV,FAC SCI,DEPT CHEM,TOYONAKA,OSAKA 560,JAPAN. RP BAKER, PJ (reprint author), NIAID,IMMUNOGENET LAB,TWINBROOK 2 RES FACILITY,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. NR 44 TC 22 Z9 22 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 JUL PY 1992 VL 60 IS 7 BP 2694 EP 2701 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA JB247 UT WOS:A1992JB24700021 PM 1535339 ER PT J AU WILBUR, WJ AF WILBUR, WJ TI AN INFORMATION MEASURE OF RETRIEVAL PERFORMANCE SO INFORMATION SYSTEMS LA English DT Article DE INFORMATION RETRIEVAL; INFORMATION THEORY; PERFORMANCE MEASURE; RECALL; PRECISION; RELEVANCE ID SYSTEM PERFORMANCE AB The classical measures of information retrieval quality, namely precision and recall, each have disadvantages depending on the circumstances. In judging the output of an automatic retrieval procedure it would be useful to have a single number which is practical to compute and summarizes the quality of the output. Such a measure could facilitate the study of retrieval methodology and clarify efforts to optimize retrieval. We show how such a measure may be defined for retrieval methods with ranked output. It is based on the change in the Shannon entropy of the distribution of relevant documents in the database that is produced by the act of retrieval. Properties of this new measure are derived and reveal that it conforms to intuitive expectations. RP WILBUR, WJ (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BLDG 38A,ROOM 8S806,BETHESDA,MD 20892, USA. NR 20 TC 16 Z9 16 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4379 J9 INFORM SYST JI Inf. Syst. PD JUL PY 1992 VL 17 IS 4 BP 283 EP 298 DI 10.1016/0306-4379(92)90019-J PG 16 WC Computer Science, Information Systems SC Computer Science GA JL916 UT WOS:A1992JL91600001 ER PT J AU NOMIZU, M UTANI, A SHIRAISHI, N YAMADA, Y ROLLER, PP AF NOMIZU, M UTANI, A SHIRAISHI, N YAMADA, Y ROLLER, PP TI SYNTHESIS AND CONFORMATION OF THE TRIMERIC COILED-COIL SEGMENT OF LAMININ SO INTERNATIONAL JOURNAL OF PEPTIDE AND PROTEIN RESEARCH LA English DT Article DE ALPHA-HELICAL PEPTIDE; CIRCULAR DICHROISM SPECTROSCOPY; COILED-COIL STRUCTURE; IKVAV SEGMENT; LAMININ; SILVER TRIFLUOROMETHANESULFONATE; SOLID-PHASE PEPTIDE SYNTHESIS; THALLIUM (III) TRIFLUORACETATE; 2-STEP HARD ACID DEPROTECTION CLEAVAGE PROCEDURE ID PHASE PEPTIDE-SYNTHESIS; CYSTINE-PEPTIDES; THALLIUM(III) TRIFLUOROACETATE; DEPROTECTING REAGENT; MULTIDOMAIN PROTEIN; CYSTEINE-PEPTIDES; GLOBULAR DOMAIN; LONG-ARM; A-CHAIN; GLYCOPROTEIN AB A disulfide linked 95-mer parallel hetero-trimeric active site segment of laminin was designed and synthesised. The three subunits, A (32-mer), B1 (30-mer) and B2 (33-mer), were prepared by Boc-based solid-phase peptide synthesis involving a two-step trimethylsilyl bromide-thioanisole and HF deprotection procedure. The interlinking of the three subunits was accomplished by the stepwise selective formation of two disulfide bridges using air-oxidation and thallium (III) trifluoroacetate oxidation. The conformations of the synthetic peptides were studied by circular dichroism (CD) spectroscopy, showing that the hetero-dimer, B1-B2, one of the homo-dimers, B1-B1, and the trimer are 30 to 40% in the (alpha-helical conformation in aqueous buffer. Variable temperature CD studies demonstrated that the trimer is considerably more stable (melting temperature (Tm) = 61-degrees) than the hetero-dimer, B1-B2 (Tm = 36-degrees). C1 NCI,MED CHEM LAB,DTP,DCT,BLDG 37,RM 5C02,BETHESDA,MD 20892. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NR 35 TC 13 Z9 13 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0367-8377 J9 INT J PEPT PROT RES JI Int. J. Pept. Protein Res. PD JUL PY 1992 VL 40 IS 1 BP 72 EP 79 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JP054 UT WOS:A1992JP05400011 PM 1428543 ER PT J AU LO, SC HAYES, MM TULLY, JG WANG, RY KOTANI, H PIERCE, PF ROSE, DL SHIH, JW AF LO, SC HAYES, MM TULLY, JG WANG, RY KOTANI, H PIERCE, PF ROSE, DL SHIH, JW TI MYCOPLASMA-PENETRANS SP-NOV, FROM THE UROGENITAL TRACT OF PATIENTS WITH AIDS SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID GENITAL MYCOPLASMAS; COLONIZATION; PNEUMONIAE; INCOGNITUS AB An unusual mycoplasma, which was isolated from the urine of a human immunodeficiency virus-positive male homosexual patient, has an elongated flask shape and two unique sharply divided internal compartments. The tiplike compartment is densely packed with fine granules, and the body compartment is loosely filled with coarse granules consistent with ribosomal structures. The organism has properties of adherence, hemadsorption, and cytadsorption and invades many different types of mammalian cells. Adhesion and penetration apparently involve the terminally located tiplike structure. Cholesterol is required for growth, and the mycoplasma ferments glucose and hydrolyzes arginine, but does not hydrolyze urea. The results of DNA homology studies revealed that this organism is not genetically related to previously described mycoplasma species that have the same biochemical properties. The results of serologic studies demonstrated that this organism is antigenically distinct from all previously described mycoplasmas. We propose that this new mollicute species should be named Mycoplasma penetrans sp. nov. The type strain is strain GTU-54-6A1 (= ATCC 55252). C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. NIAID,MOLEC MICROBIOL LAB,FREDERICK,MD 21710. GEORGETOWN UNIV HOSP,HIV CLIN PROGRAM,WASHINGTON,DC 20007. RP LO, SC (reprint author), ARMED FORCES INST PATHOL,DEPT INFECT & PARASIT DIS PATHOL,WASHINGTON,DC 20306, USA. FU NIAID NIH HHS [AI-31830] NR 40 TC 73 Z9 76 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD JUL PY 1992 VL 42 IS 3 BP 357 EP 364 PG 8 WC Microbiology SC Microbiology GA JE083 UT WOS:A1992JE08300003 PM 1503969 ER PT J AU LOUIE, KG HAMILTON, TC SHOEMAKER, RH YOUNG, RC OZOLS, RF AF LOUIE, KG HAMILTON, TC SHOEMAKER, RH YOUNG, RC OZOLS, RF TI EVALUATION OF INVITRO DRUG SCREENING LEADS USING EXPERIMENTAL-MODELS OF HUMAN OVARIAN-CANCER SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE DRUG SCREENING FOR OVARIAN CANCER ID COLONY-FORMING ASSAY; PROGRAM; CELLS AB Five compounds which were identified as potential new anticancer drugs in in vitro screening with the human tumor colony forming assay were selected for further evaluation using in vitro and in vivo models of human ovarian cancer. Three of five compounds were found to inhibit in vitro colony formation of ovarian cancer cell lines derived from both untreated and combination chemotherapy refractory patients. One compound was also found to prolong survival in a human ovarian carcinoma xenograft model system. This compound, chloroquinoxaline sulfonamide, was selected for development and has shown preliminary indication of activity in phase I clinical testing. C1 NCI,DIV CANC TREATMENT,SURG BRANCH,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,DEV THERAPEUT BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CM-07419, N01-CM-07327, N01-CM-07251] NR 14 TC 4 Z9 4 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD JUL PY 1992 VL 10 IS 2 BP 73 EP 78 DI 10.1007/BF00873120 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA JF515 UT WOS:A1992JF51500002 PM 1500268 ER PT J AU HEALY, B AF HEALY, B TI RESEARCH OFFERS NEW HOPE FOR YOUNG PERSONS WITH DIABETES SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP HEALY, B (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 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 JUL 1 PY 1992 VL 268 IS 1 BP 20 EP 20 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA JA165 UT WOS:A1992JA16500004 PM 1608101 ER PT J AU BURRIS, AS BANKS, SM CARTER, CS DAVIDSON, JM SHERINS, RJ AF BURRIS, AS BANKS, SM CARTER, CS DAVIDSON, JM SHERINS, RJ TI A LONG-TERM, PROSPECTIVE-STUDY OF THE PHYSIOLOGICAL AND BEHAVIORAL-EFFECTS OF HORMONE REPLACEMENT IN UNTREATED HYPOGONADAL MEN SO JOURNAL OF ANDROLOGY LA English DT Article DE SEXUAL BEHAVIOR; ANDROGENS; MOOD; ERECTION ID NOCTURNAL PENILE TUMESCENCE; SEXUAL-BEHAVIOR; ANDROGEN; THERAPY; RIGIDITY; MALES AB This study describes sexual activity, nocturnal penile erections, and mood states as a function of serum levels of androgens in previously untreated hypogonadal men before and during hormone replacement, selected infertile men (elevated serum follicle-stimulating hormone levels), and normal men. Nocturnal penile tumescence and rigidity were measured with a portable monitor, and sexual activity and mood were assessed by prospective, self-reported written forms. Nocturnal erections were absent or of very low amplitude and duration in the untreated hypogonadal men compared to the infertile and normal men. Nocturnal erections increased steadily during hormone replacement and were in the normal range within 6 to 12 months of treatment. In contrast, serum testosterone concentration rapidly reached the upper range of normal. During treatment, the hypogonadal men reported increases in several aspects of sexual activity, including sexual interest and the number of spontaneous erections. On mood inventories, the untreated hypogonadal men scored significantly higher in ratings of depression, anger, fatigue, and confusion than did infertile and normal men. During hormonal replacement therapy these scores decreased, although the hypogonadal men continued to score higher in "depression" than did infertile and normal men. In most instances, the men with infertility and the normal men were statistically indistinguishable in nocturnal penile tumescence and rigidity parameters, self-reported sexual activity, and mood state. These data support the hypothesis that androgen treatment increases nocturnal and spontaneous erections, and sexual interest, and has some capacity to improve mood. C1 UNIV MARYLAND,DEPT ZOOL,COLL PK,MD 20742. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NIAID,OFF SCI DIRECTOR,BETHESDA,MD 20892. STANFORD UNIV,DEPT PHYSIOL,STANFORD,CA 94305. NR 22 TC 174 Z9 176 U1 0 U2 0 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 SN 0196-3635 J9 J ANDROL JI J. Androl. PD JUL-AUG PY 1992 VL 13 IS 4 BP 297 EP 304 PG 8 WC Andrology SC Endocrinology & Metabolism GA JH789 UT WOS:A1992JH78900002 PM 1399830 ER PT J AU BIRRER, P MCELVANEY, NG GILLISSEN, A HOYT, RF BLOEDOW, DC HUBBARD, RC CRYSTAL, RG AF BIRRER, P MCELVANEY, NG GILLISSEN, A HOYT, RF BLOEDOW, DC HUBBARD, RC CRYSTAL, RG TI INTRAVENOUS RECOMBINANT SECRETORY LEUKOPROTEASE INHIBITOR AUGMENTS ANTINEUTROPHIL ELASTASE DEFENSE SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE NEUTROPHIL ELASTASE; BRONCHOSCOPY; ANIMAL ID LEUKOCYTE-PROTEASE INHIBITOR; INTERSTITIAL LUNG-DISEASES; LOWER RESPIRATORY-TRACT; NEUTROPHIL ELASTASE; PROTEINASE-INHIBITOR; CHRONIC INFLAMMATION; CYSTIC-FIBROSIS; UNKNOWN CAUSE; PSEUDOMONAS; EMPHYSEMA AB Secretory leukoprotease inhibitor (SLPI), a 12-kDa serine antiprotease, normally protects the upper airway epithelial surface from attack by neutrophil elastase (NE). In the context that a variety of inflammatory lung diseases are characterized by large neutrophil burdens with resultant high levels of NE in the lung, recombinant SLPI (rSLPI), a molecule identical to natural SLPI, may be an effective means to augment the anti-NE protective screen of the lung. To determine whether intravenous rSLPI will augment respiratory tract and epithelial surface levels of SLPI and anti-NE capacity, rSLPI was administered intravenously to sheep and SLPI levels were quantified in plasma, lung lymph (as a measure of lung interstitial levels), lung epithelial lining fluid (ELF), and urine. rSLPI (1 g) was administered over 10 min, and after 30 min plasma levels of SLPI were 8-mu-M and decreased with a half-life of 1.8 h. Lymph SLPI levels paralleled the plasma levels: 4 h after infusion the lymph-to-plasma ratio was 0.8. ELF SLPI levels paralleled the lymph levels: 4 h after infusion the ELF-to-lymph ratio was 0.3. Western analysis demonstrated intact SLPI in lymph and ELF, and functional analysis showed increases in lymph and ELF anti-NE capacity that paralleled the levels of SLPI. As might be expected from a protein with a molecular mass of 12 kDa, urine excretion was high, with 20% of the SLPI excreted over 5 h. However, if the rate of infusion was slowed, SLPI excretion decreased significantly, with a 3-h infusion associated with 9% excretion and a 12-h infusion associated with <0.2% excretion. Importantly, slowing the infusion rate was associated with only a mild decrease in lung delivery, with ELF levels 2 h after a 12-h infusion 65% of ELF levels 2 h after a 10-min infusion. Thus, intravenous rSLPI administration can markedly augment the anti-NE defenses of the lung, and by slowing the rate of rSLPI administration, urinary excretion of SLPI can be markedly curtailed without consequent loss of delivery of the molecule to the target organ. C1 NHLBI,PULM BRANCH,BLDG 10,RM 6D03,BETHESDA,MD 20892. NHLBI,LAB ANIM MED & SURG SECT,BETHESDA,MD 20892. SYNERGEN,BOULDER,CO 80301. RI McElvaney, Noel/A-6809-2010 NR 44 TC 25 Z9 26 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JUL PY 1992 VL 73 IS 1 BP 317 EP 323 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA JE703 UT WOS:A1992JE70300044 PM 1354669 ER PT J AU ANKENBAUER, RG AF ANKENBAUER, RG TI CLONING OF THE OUTER-MEMBRANE HIGH-AFFINITY FE(III)-PYOCHELIN RECEPTOR OF PSEUDOMONAS-AERUGINOSA SO JOURNAL OF BACTERIOLOGY LA English DT Article ID FERRIPYOCHELIN-BINDING PROTEIN; GRAM-NEGATIVE BACTERIA; ESCHERICHIA-COLI; SURFACE EXPRESSION; IRON TRANSPORT; DNA CLONING; SIDEROPHORE; PYOCHELIN; MUTANTS; VIRULENCE AB Pseudomonas aeruginosa produces the phenolic siderophore pyochelin under iron-limiting conditions. In this study, an Fe(III)-pyochelin transport-negative (Fpt-) strain, IA613, was isolated and characterized. Fe-55(III)-pyochelin transport assays determined that no Fe(III)-pyochelin associated with the Fpt- IA613 cells while a significant amount associated with KCN-poisoned Fpt+ cells. A P. aeruginosa genomic library was constructed in the IncP cosmid pLAFR1. The genomic library was mobilized into IA613, and a recombinant cosmid, pCC41, which complemented the Fpt- phenotype of IA613, was isolated. pCC41 contained a 28-kb insert of P. aeruginosa DNA, and the Fpt--complementing region was localized to a 3.6-kb BamHI-EcoRI fragment by deletion and subcloning of the insert. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of IA613 revealed that it lacked a 75-kDa outer membrane protein present in Fpt+ strains. IA613 strains bearing plasmid pRML303, which carries the 3.6-kb BamHI-EcoRI fragment of pCC41, expressed the 75-kDa outer membrane protein and demonstrated a Fe-55(III)-pyochelin transport phenotype identical to that of a wild-type Fpt+ strain. Minicell analysis demonstrated that the 3.6-kb BamHI-EcoRI fragment of pCC41 encoded a protein of approximately 75 kDa. The results presented here and in a previous report (D. E. Heinrichs, L. Young, and K. Poole, Infect. Immun. 59:3680-3684, 1991) lead to the conclusion that the 75-kDa outer membrane protein is the high-affinity receptor for Fe(III)-pyochelin in P. aeruginosa. RP ANKENBAUER, RG (reprint author), NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840, USA. FU NIAID NIH HHS [AI13120] NR 46 TC 29 Z9 29 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 JUL PY 1992 VL 174 IS 13 BP 4401 EP 4409 PG 9 WC Microbiology SC Microbiology GA JB456 UT WOS:A1992JB45600027 PM 1320609 ER PT J AU DIMRI, GP RUDD, KE MORGAN, MK BAYAT, H AMES, GFL AF DIMRI, GP RUDD, KE MORGAN, MK BAYAT, H AMES, GFL TI PHYSICAL MAPPING OF REPETITIVE EXTRAGENIC PALINDROMIC SEQUENCES IN ESCHERICHIA-COLI AND PHYLOGENETIC DISTRIBUTION AMONG ESCHERICHIA-COLI STRAINS AND OTHER ENTERIC BACTERIA SO JOURNAL OF BACTERIOLOGY LA English DT Article ID DNA-SEQUENCES; REP SEQUENCES; PROTEIN; MAP; RNA; BIOSYNTHESIS; ORGANIZATION; EXPRESSION; CHROMOSOME; ALIGNMENT AB Repetitive extragenic palindromic (REP) sequences are highly conserved inverted repeat sequences originally discovered in Escherichia coli and Salmonella typhimurium. We have physically mapped these sequences in the E. coli genome by using Southern hybridization of an ordered phage bank of E. coli (Y. Kohara, K. Akiyama, and K. Isono, Cell 50:495-508, 1987) with generic REP probes derived from the REP consensus sequence. The set of REP probe-hybridizing clones was correlated with a set of clones expected to contain REP sequences on the basis of computer searches. We also show that a generic REP probe can be used in Southern hybridization to analyze genomic DNA digested with restriction enzymes to determine genetic relatedness among natural isolates of E. coli. A search for these sequences in other members of the family Enterobacteriaceae shows a consistent correlation between both the number of occurrences and the hybridization strength and genealogical relationship. C1 UNIV CALIF BERKELEY,DEPT MOLEC & CELL BIOL,DIV BIOCHEM & MOLEC BIOL,401 BARKER HALL,BERKELEY,CA 94720. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. FU NIGMS NIH HHS [GM39415, 1-F32 GM12156] NR 44 TC 48 Z9 51 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUL PY 1992 VL 174 IS 14 BP 4583 EP 4593 PG 11 WC Microbiology SC Microbiology GA JE399 UT WOS:A1992JE39900007 PM 1624447 ER PT J AU VUISTER, GW BAX, A AF VUISTER, GW BAX, A TI MEASUREMENT OF 2-BOND JCOH ALPHA COUPLING-CONSTANTS IN PROTEINS UNIFORMLY ENRICHED WITH C-13 SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE 2-BOND J-COUPLING; C-13 ENRICHMENT; PSI ANGLE; PROTEIN BACKBONE; E-COSY ID 2D NMR-SPECTRA; 3-DIMENSIONAL NMR; SPECTROSCOPY; ASSIGNMENTS AB A simple E.COSY type technique is described for measurement of two-bond J(COH-alpha) coupling constants in proteins that are uniformly enriched with C-13. The method has been used to measure 2J(COH-alpha) for 132 residues in the proteins calmodulin and staphylococcal nuclease having non-overlapping H(alpha)-C(alpha) correlations. Measured 2J(COH-alpha) coupling constants fall in the 0 to -9.5 Hz range. A separate experiment, measuring the accuracy of these values, indicates a root-mean-square error of 1 Hz. Comparison of the J couplings with the dihedral backbone angles from crystallographic studies confirms a weak but statistically significant correlation between the dihedral angle-psi and the magnitude of 2J(COH-alpha), but also indicates that parameters other than psi have a significant effect on the value of the coupling. RP VUISTER, GW (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. NR 25 TC 50 Z9 50 U1 0 U2 2 PU ESCOM SCI PUBL BV PI LEIDEN PA PO BOX 214, 2300 AE LEIDEN, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD JUL PY 1992 VL 2 IS 4 BP 401 EP 405 DI 10.1007/BF01874818 PG 5 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA JF969 UT WOS:A1992JF96900009 PM 1511238 ER PT J AU IBARAKI, K TERMINE, JD WHITSON, SW YOUNG, MF AF IBARAKI, K TERMINE, JD WHITSON, SW YOUNG, MF TI BONE-MATRIX MESSENGER-RNA EXPRESSION IN DIFFERENTIATING FETAL BOVINE OSTEOBLASTS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID DEDUCED PROTEIN-SEQUENCE; NODULES FORMED INVITRO; SMALL PROTEOGLYCAN-I; ALKALINE-PHOSPHATASE; DEVELOPMENTAL EXPRESSION; INSITU HYBRIDIZATION; CELLS; RAT; OSTEONECTIN; OSTEOPONTIN AB In the accompanying study, we report an in vitro culture system from bovine bone cells that can be applied to investigate bone cell growth and differentiation. In this system, bovine bone cells placed in mineralization medium formed multilayers (days 2-3), began deposition of mineral (days 5-6), and eventually acquired a mineralized matrix sheet (days 14-20) through the stages of mineralizing nodules and trabecular-like structure. In the current study we used this system to investigate the relative expression of bone matrix genes that may play an important role in bone development and metabolism. alpha-1(I)-collagen, alkaline phosphatase, osteonectin, biglycan (PgI), decorin (PgII), osteopontin, and bone sialoprotein mRNA gene expression were measured on days 0, 2, 6, 10, and 20 (date when the cells were placed in mineralization medium as day 0). Total RNA was purified and analyzed by northern blot using radiolabeled cDNA encoding these genes. To comprehend the relationship between gene expression and mineralization, total calcium content in the cultures was also measured. During the culture period we observed several very different gene expression profiles. The expression of both alpha-1(I)-collagen and biglycan increased 3- to 4-fold by day 6 and then returned to basal levels by day 20. The osteonectin gene was highly expressed throughout the culture, with no significant increase in induction found during any time of culture. A significant induction of alkaline phosphatase (13.8-fold) gene expression was observed by day 6. Osteopontin showed a similar profile to that of alkaline phosphatase but had a much greater level of relative expression (26-fold) compared to day 0. Interestingly, downregulation during mineral accumulation seemed a common occurrence among many of the genes measured. In contrast, the bone sialoprotein gene showed a significant and distinct expression pattern, increasing rapidly after the onset of mineralization on day 6 and ultimately reaching 140-fold that of day 0. Decorin (Pg 11) showed an increasing pattern, with the final relative level of induction 5-fold on day 20. These data suggest that the development of the mature osteoblastic phenotype, complete with the ability to produce a thick mineralized matrix, requires the differential regulation of a series of genes and their gene products over the culture period. RP IBARAKI, K (reprint author), NIDR,BONE RES BRANCH,BLDG 30,ROOM 106,BETHESDA,MD 20892, USA. NR 47 TC 140 Z9 141 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUL PY 1992 VL 7 IS 7 BP 743 EP 754 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JD680 UT WOS:A1992JD68000003 PM 1642143 ER PT J AU HOLLEY, MC KALINEC, F KACHAR, B AF HOLLEY, MC KALINEC, F KACHAR, B TI STRUCTURE OF THE CORTICAL CYTOSKELETON IN MAMMALIAN OUTER HAIR-CELLS SO JOURNAL OF CELL SCIENCE LA English DT Article DE OUTER HAIR CELLS; CYTOSKELETON; CELL CORTEX; CELL SHAPE; CELL MOTILITY ID GUINEA-PIG COCHLEA; ELECTROKINETIC SHAPE CHANGES; ALPHA-ACTININ; ERYTHROCYTE-MEMBRANE; DEOXYRIBONUCLEASE-I; ORGAN; LENGTH; SKELETON; SPECTRIN; ULTRASTRUCTURE AB The cortical cytoskeletal lattice in outer hair cells is a two-dimensional actin-based structure, which can be labelled with rhodamine/phalloidin and disrupted by the enzyme deoxyribonuclease I. Structural information from thin sectioned, freeze-etched and negatively stained preparations shows that it is based upon two types of filament that form a cross-linked lattice of circumferential filaments. The cross-links are 70-80 nm long. Measurements of the spacing between circumferential filaments suggest that the lattice is stiffer circumferentially than it is longitudinally. Analysis of the orientation of circumferential filaments shows that it is composed of discrete domains of up to 10-mu-m2. Relative movements between domains could allow substantial changes of cell shape without disrupting the unit structure of the lattice, thus allowing the cell cortex to retain its elastic responses to high-frequency deformations. C1 NIDCD,CELL BIOL LAB,BLDG 10,ROOM 5D46,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. UNIV WALK,SCH MED SCI,DEPT PHYSIOL,BRISTOL BS8 1TD,ENGLAND. OI Holley, Matthew/0000-0001-9547-1953 FU Wellcome Trust NR 45 TC 103 Z9 105 U1 3 U2 4 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 JUL PY 1992 VL 102 BP 569 EP 580 PN 3 PG 12 WC Cell Biology SC Cell Biology GA JG803 UT WOS:A1992JG80300019 PM 1506434 ER PT J AU ISHAC, EJN LAZARWESLEY, E KUNOS, G AF ISHAC, EJN LAZARWESLEY, E KUNOS, G TI RAPID INVERSE CHANGES IN ALPHA-1B-ADRENERGIC AND BETA-2-ADRENERGIC RECEPTORS AND GENE TRANSCRIPTS IN ACUTELY ISOLATED RAT-LIVER CELLS SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID BETA-ADRENERGIC RECEPTORS; ALPHA-1-ADRENERGIC RECEPTOR; GLYCOGEN-PHOSPHORYLASE; PRIMARY CULTURE; ADENYLATE-CYCLASE; CYCLIC-AMP; ISOLATED HEPATOCYTES; MOLECULAR-CLONING; RESPONSIVENESS; ADRENOCEPTOR AB In vitro incubation of hepatocytes acutely isolated from adult male rats leads to a rapid conversion of the adrenergic activation of glycogenolysis from an alpha-1-receptor (alpha-1AR) to a beta-2-receptor (beta-2AR) mediated response within 4 h. In order to understand the underlying mechanism, we examined time-dependent changes in alpha-1,- and beta-2-adrenergic activation of glycogenolysis and second messenger systems, the cellular density and affinity of alpha-1AR and beta-2AR, and the steady state levels of alpha-(1B)AR and beta-2AR mRNAs. Incubation of hepatocytes for 4 h resulted in a decrease in phosphorylase activation and inositol 1,4,5 trisphosphate accumulation in response to phenylephrine, a 40% decrease in alpha-1AR density, and a 70% decrease in alpha(1B)AR mRNA levels. Incubation of hepatocytes for 4 h also resulted in the emergence of a phosphorylase response to isoproterenol, an increase in isoproterenol-induced but not in glucagon- or forskolin-induced cAMP accumulation, no significant change in beta-2AR density, and a twofold increase in beta-2AR mRNA levels. Exposure of cells to cycloheximide, 2-mu-M throughout the 4 h incubation, prevented the emergence of the phosphorylase response to isoproterenol and reduced beta-2AR densities, while the decrease in alpha-1AR density was not affected and the decrease in phosphorylase activation by phenylephrine was attenuated. The results indicate that dissociation of rat liver cells triggers a rapidly developing decrease in alpha(1B)AR mRNA and increase in beta-2AR mRNA levels and corresponding inverse changes in the synthesis of alpha(1B)AR and beta-2AR which account, at least in part, for the rapid conversion from alpha-1- to beta-2-adrenergic glycogenolysis. C1 NIAAA,PHYSIOL & PHARMACOL STUDIES LAB,BETHESDA,MD 20852. NR 41 TC 24 Z9 24 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUL PY 1992 VL 152 IS 1 BP 79 EP 86 DI 10.1002/jcp.1041520111 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA JC609 UT WOS:A1992JC60900010 PM 1320040 ER EF