FN Thomson Reuters Web of Science™ VR 1.0 PT J AU BAX, A DELAGLIO, F GRZESIEK, S VUISTER, GW AF BAX, A DELAGLIO, F GRZESIEK, S VUISTER, GW TI RESONANCE ASSIGNMENT OF METHIONINE METHYL-GROUPS AND CHI(3) ANGULAR INFORMATION FROM LONG-RANGE PROTON-CARBON AND CARBON-CARBON J-CORRELATION IN A CALMODULIN PEPTIDE COMPLEX SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE CALMODULIN; CARBON-CARBON J COUPLING; CARBON PROTON J COUPLING; HMBC; METHIONINE; PROTEIN NMR; 3D NMR; ISOTOPE LABELING ID MULTIDIMENSIONAL NMR; C-13-ENRICHED PROTEINS; COUPLING-CONSTANTS; C-13; 2D; SPECTRA; RECOGNITION; MAGNETIZATION; 2-BOND; PHASE AB Several simple 3D experiments are used to provide J correlations between methionine C-epsilon methyl carbons and either the (CH2)-H-gamma protons or C-beta and C-gamma. The intensity of the J correlations provides information on the size of the three-bond J couplings and thereby on the chi(3) torsion angle. In addition, a simple 3D version of the HMBC experiment provides a sensitive link between the (CH3)-H-epsilon methyl protons and C-gamma. The methods are demonstrated for a 20 kDa complex between calmodulin and a 26-residue peptide fragment of skeletal muscle myosin light chain kinase. RP BAX, A (reprint author), NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892, USA. NR 25 TC 47 Z9 47 U1 0 U2 3 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 NOV PY 1994 VL 4 IS 6 BP 787 EP 797 DI 10.1007/BF00398409 PG 11 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA PQ823 UT WOS:A1994PQ82300004 PM 7812153 ER PT J AU KUBONIWA, H GRZESIEK, S DELAGLIO, F BAX, A AF KUBONIWA, H GRZESIEK, S DELAGLIO, F BAX, A TI MEASUREMENT OF H-N-H-ALPHA J-COUPLINGS IN CALCIUM-FREE CALMODULIN USING NEW 2D AND 3D WATER-FLIP-BACK METHODS SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE 3-BOND J COUPLING; 3D NMR; QUANTITATIVE J CORRELATION; CALMODULIN ID NMR-SPECTROSCOPY; ACCURATE MEASUREMENTS; CONSTANTS 3JHN-ALPHA; RESONANCE EXPERIMENT; PROTEINS; SPECTRA; POLYPEPTIDES; RELAXATION; ANGLES; PHASE AB Two new methods are described for the measurement of three-bond J(HNH alpha) couplings in proteins isotopically enriched with N-15. Both methods leave the water magnetization in an unsaturated state, parallel to the z-axis, and therefore offer significant enhancements in sensitivity for rapidly exchanging backbone amide protons. The J couplings can be measured either from a set of constant-time 2D H-1-N-15 HMQC spectra, which are modulated in intensity by J(HNH alpha) or from a water-flip-back version of the 3D HNHA experiment. The method is demonstrated for a sample of calcium-free calmodulin. Residues Lys(75)-Asp(80) have J(HNH alpha) values in the 6-7 Hz range, suggesting that a break in the 'central helix' occurs at the same position as previously observed in solution NMR studies of Ca2+-ligated calmodulin. RP KUBONIWA, H (reprint author), NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892, USA. NR 25 TC 318 Z9 319 U1 1 U2 4 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 NOV PY 1994 VL 4 IS 6 BP 871 EP 878 DI 10.1007/BF00398416 PG 8 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA PQ823 UT WOS:A1994PQ82300011 PM 7812158 ER PT J AU YANG, YM SPITZER, E KENNEY, N ZSCHIESCHE, W LI, ML KROMMINGA, A MULLER, T SPENER, F LEZIUS, A VEERKAMP, JH SMITH, GH SALOMON, DS GROSSE, R AF YANG, YM SPITZER, E KENNEY, N ZSCHIESCHE, W LI, ML KROMMINGA, A MULLER, T SPENER, F LEZIUS, A VEERKAMP, JH SMITH, GH SALOMON, DS GROSSE, R TI MEMBERS OF THE FATTY-ACID-BINDING PROTEIN FAMILY ARE DIFFERENTIATION FACTORS FOR THE MAMMARY-GLAND SO JOURNAL OF CELL BIOLOGY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; CASEIN GENE-EXPRESSION; EPITHELIAL-CELLS; INHIBITOR MDGI; RAT-LIVER; DUCTAL MORPHOGENESIS; EXTRACELLULAR-MATRIX; ARACHIDONIC-ACID; TRANSGENIC MICE; MESSENGER-RNA AB Mammary gland development is controlled by systemic hormones and by growth factors that might complement or mediate hormonal action. Peptides that locally signal growth cessation and stimulate differentiation of the developing epithelium have not been described. Here, we report that recombinant and wild-type forms of mammary-derived growth inhibitor (MDGI) and heart-fatty acid binding protein (FABP), which belong to the FABP family, specifically inhibit growth of normal mouse mammary epithelial cells (MEC), while growth of stromal cells is not suppressed. In mammary gland organ culture, inhibition of ductal growth is associated with the appearance of bulbous alveolar end buds and formation of fully developed lobuloalveolar structures. In parallel, MDGI stimulates its own expression and promotes milk protein synthesis. Selective inhibition of endogenous MDGI expression in MEC by antisense phosphorothioate oligonucleotides suppresses appearance of alveolar end buds and lowers the beta-casein level in organ cultures. Furthermore, MDGI suppresses the mitogenic effects of epidermal growth factor, and epidermal growth factor antagonizes the activities of MDGI. Finally, the regulatory properties of MDGI can be fully mimicked by an 11-amino acid sequence, represented in the COOH terminus of MDGI and a subfamily of structurally related FABPs. This peptide does not bind fatty acids. To our knowledge, this is the first report about a growth inhibitor promoting mammary gland differentiation. C1 MAX DELBRUCK CTR MOLEC MED,D-13122 BERLIN,GERMANY. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. UNIV MUNSTER,INST BIOCHEM,D-48149 MUNSTER,GERMANY. UNIV NIJMEGEN,DEPT BIOCHEM,NIJMEGEN,NETHERLANDS. NIH,FOGARTY INT CTR,BETHESDA,MD 20892. NR 74 TC 96 Z9 98 U1 0 U2 1 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 NOV PY 1994 VL 127 IS 4 BP 1097 EP 1109 DI 10.1083/jcb.127.4.1097 PG 13 WC Cell Biology SC Cell Biology GA PT483 UT WOS:A1994PT48300017 PM 7962070 ER PT J AU ZIMMER, A ZIMMER, AM REYNOLDS, K AF ZIMMER, A ZIMMER, AM REYNOLDS, K TI TISSUE-SPECIFIC EXPRESSION OF THE RETINOIC ACID RECEPTOR-BETA-2 - REGULATION BY SHORT OPEN READING FRAMES IN THE 5'-NONCODING REGION SO JOURNAL OF CELL BIOLOGY LA English DT Article ID DEPENDENT PROTEIN-KINASE; 5' UNTRANSLATED REGION; TRANSLATIONAL CONTROL; MESSENGER-RNA; INITIATION FACTOR-2-ALPHA; MALIGNANT TRANSFORMATION; TRANSGENIC MICE; CELLS; GCN4; GENE AB The 40-S subunit of eukaryotic ribosomes binds to the capped 5'end of mRNA and scans for the first AUG in a favorable sequence context to initiate translation. Most eukaryotic mRNAs therefore have a short 5'untranslated region (5'-UTR) and no AUGs upstream of the translational start site; features that seem to assure efficient translation. However, similar to 5-10% of all eukaryotic mRNAs, particularly those encoding for regulatory proteins, have complex leader sequences that seem to compromise translational initiation. The retinoic-acid-receptor-beta 2 (RAR beta 2) mRNA is such a transcript with a long (461 nucleotides) 5'-UTR that contains five, partially overlapping, upstream open reading frames (uORFs) that precede the major ORE We have begun to investigate the function of this complex 5'-UTR in transgenic mice, by introducing mutations in the start/stop codons of the uORFs in RAR beta 2-lacZ reporter constructs. When we compared the expression patterns of mutant and wild-type constructs we found that these mutations affected expression of the downstream RAR beta 2-ORF, resulting in an altered regulation of RAR beta 2-lacZ expression in heart and brain. Other tissues were unaffected. RNA analysis of adult tissues demonstrated that the uORFs act at the level of translation; adult brains and hearts of transgenic mice carrying a construct with either the wild-type or a mutant UTR, had the same levels of mRNA, but only the mutant produced protein. Our study outlines an unexpected role for uORFs: control of tissue-specific and developmentally regulated gene expression. RP ZIMMER, A (reprint author), NIMH,CELL BIOL LAB,DEV BIOL UNIT,BLDG 36-3A17,BETHESDA,MD 20892, USA. RI Zimmer, Andreas/B-8357-2009 NR 40 TC 72 Z9 72 U1 0 U2 0 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 NOV PY 1994 VL 127 IS 4 BP 1111 EP 1119 DI 10.1083/jcb.127.4.1111 PG 9 WC Cell Biology SC Cell Biology GA PT483 UT WOS:A1994PT48300018 PM 7962071 ER PT J AU MAUPIN, P PHILLIPS, CL ADELSTEIN, RS POLLARD, TD AF MAUPIN, P PHILLIPS, CL ADELSTEIN, RS POLLARD, TD TI DIFFERENTIAL LOCALIZATION OF MYOSIN-II ISOZYMES IN HUMAN CULTURED-CELLS AND BLOOD-CELLS SO JOURNAL OF CELL SCIENCE LA English DT Article DE CLEAVAGE FURROW; CYTOKINESIS; FLUORESCENCE MICROSCOPY; MYOSIN-II ID HEAVY-CHAIN GENE; NONMUSCLE MYOSIN; ACTIN-FILAMENTS; CONTRACTILE RING; CLEAVAGE FURROW; MITOTIC SPINDLE; CELLULAR MYOSIN; MESSENGER-RNAS; STRESS FIBERS; GROWTH AB We used purified polyclonal antibodies to human cytoplasmic myosin-IIA and myosin-IIB directly labeled with fluorescent dyes to localize these myosin-II isozymes in HeLa cells, melanoma cells and blood cells, Both antibodies react strongly with myosin-II isozymes in HeLa cells, melanoma cells and blood eosinophils, but only anti-myosin-IIA antibodies stain platelets, lymphocytes, neutrophils and monocytes in smears of human blood, Both antibodies stain small spots along the stress fibers of interphase HeLa cells and melanoma cells, but double staining revealed that the detailed distributions of myosin-IIA and myosin-IIB differ, A low concentration of diffuse myosin-IIB is present in the cortex, both in lamellar regions around the periphery of the cell and over the free surface, Myosin-IIB is also concentrated in spots along perinuclear stress fibers, Myosin-IIA is absent from the cortex but is concentrated in spots along stress fibers located near the basal surface of cultured cells, This population of peripheral stress fibers is highly enriched in myosin-IIA relative to myosin-IIB, but both are found together in centrally located stress fibers, In prophase and metaphase both isozymes are concentrated in the cortex in small spots less than 04 mu m in size, similar to those in stress fibers, As the chromosomes begin the separate at anaphase, most of the myosin-II spots become concentrated in the outer 0.7 mu m of the equatorial cortex in 100% of cells, This concentration of myosin-II isozymes in the cleavage furrow is maintained until the daughter cells separate, The superimposition of these small spots concentrated in the cleavage furrow produces the intense, uniform staining observed in conventional micrographs of whole cells, C1 JOHNS HOPKINS UNIV,SCH MED,DEPT CELL BIOL & ANAT,BALTIMORE,MD 21205. NHLBI,MOLEC CARDIOL LAB,BETHESDA,MD 20892. OI Phillips, Carrie/0000-0002-0256-0736; Adelstein, Robert/0000-0002-8683-2144; Aljarah, Ali/0000-0003-0535-090X FU NIGMS NIH HHS [GM-26132] NR 34 TC 178 Z9 180 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD NOV PY 1994 VL 107 BP 3077 EP 3090 PN 11 PG 14 WC Cell Biology SC Cell Biology GA PV959 UT WOS:A1994PV95900011 PM 7699007 ER PT J AU TOZEREN, A KLEINMAN, HK WU, S MERCURIO, AM BYERS, SW AF TOZEREN, A KLEINMAN, HK WU, S MERCURIO, AM BYERS, SW TI INTEGRIN ALPHA(6)BETA(4) MEDIATES DYNAMIC INTERACTIONS WITH LAMININ SO JOURNAL OF CELL SCIENCE LA English DT Article DE LAMININ; INTEGRIN; ALPHA(6)BETA(4); DYNAMICS; ADHESION ID COLON-CARCINOMA CELLS; MONOCLONAL-ANTIBODIES; FIBRONECTIN RECEPTOR; EXTRACELLULAR-MATRIX; BASEMENT-MEMBRANES; ADHESION; ALPHA-6-BETA-4; MIGRATION; SUBUNIT; LINES AB We present here a novel form of dynamic adhesion in which both the integrin receptor and the ligand supporting dynamic adhesion have been identified. Laminar flow assays showed that laminin supported attachment of alpha(6) beta(4)-positive cells in the presence of fluid shear stress (tau less than or equal to 2 dyn/cm(2)), indicating that these cells adhered to laminin within a fraction of a second. Further increases in flow rate (3.5 dyn/cm(2) less than or equal to tau less than or equal to 100 dyn/cm(2)) dyn/cm(2)) initiated rolling of attached cells in the direction of how, suggesting that rapidly formed adhesion is reversible and repeatable. Laminin fragment E8, which interacts with alpha(6) integrins, supported dynamic attachment and rolling but extracellular matrix glycoprotein fibronectin did not. In cell lines that express alpha(6) beta(4) but not alpha(6) beta(1) an anti-alpha(6) monoclonal antibody inhibited attachment to laminin in the presence of flow and following 5 minutes of static incubation. Infusion of this antibody onto cells adherent to laminin-coated slides led to rapid detachment of cells from the substratum. An anti-beta(1) monoclonal antibody diminished adhesion strength following static incubation but did not inhibit rapid attachment and flow-initiated rolling. These results indicate that in some alpha(6) beta(4)-expressing epithelial and carcinoma cell lines, integrin alpha(6) beta(4) mediates rapidly formed dynamic interactions with laminin. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. HARVARD UNIV,DEACONESS HOSP,SCH MED,CANC BIOL LAB,BOSTON,MA 02115. GEORGETOWN UNIV,DEPT CELL BIOL,WASHINGTON,DC 20007. GEORGETOWN UNIV,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. RP TOZEREN, A (reprint author), CATHOLIC UNIV AMER,DEPT MECH ENGN,WASHINGTON,DC 20064, USA. NR 46 TC 54 Z9 54 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD NOV PY 1994 VL 107 BP 3153 EP 3163 PN 11 PG 11 WC Cell Biology SC Cell Biology GA PV959 UT WOS:A1994PV95900019 PM 7699012 ER PT J AU WU, AJ KURRASCH, RH KATZ, J FOX, PC BAUM, BJ ATKINSON, JC AF WU, AJ KURRASCH, RH KATZ, J FOX, PC BAUM, BJ ATKINSON, JC TI EFFECT OF TUMOR-NECROSIS-FACTOR-ALPHA AND INTERFERON-GAMMA ON THE GROWTH OF A HUMAN SALIVARY-GLAND CELL-LINE SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID HLA-DR EXPRESSION; SJOGRENS-SYNDROME; CLASS-II; RECURRENT PAROTITIS; ADHESION MOLECULES; FACTOR RECEPTORS; IFN-GAMMA; INDUCTION; ANTIGENS; CLONING AB Interferon-gamma (IFN-gamma) is a product of activated T-lymphocytes, and tumor necrosis factor-alpha (TNF-alpha) is a product of both lymphocytes and macrophages. These cell types are often present at sites of tissue damage secondary to chronic infection or autoimmune disease. The purpose of this study was to characterize the effects of TNF-alpha and IFN-gamma on a human submandibular gland epithelial cell line (HSG). IFN-gamma caused a concentration-dependent decrease in HSG cell growth (similar to-70% in 6 days). Conversely, TNF-alpha alone had little effect on the growth of these cells. When these cytokines were added in combination (20 units/ml TNF-alpha and 1,000 units/ml of IFN-gamma), there was a synergistic antiproliferative effect; no apparent cell growth was observed. The cytokine-induced antiproliferative effect was reversible. After the apparent cessation of cell growth for 3-6 days, removal of the cytokines permitted complete growth recovery. Further, cells that recovered and exhibited growth patterns that were similar to control cells remained susceptible to the antiproliferative effects of the cytokines. Flow cytometry revealed that the percentage of cells in G0/G1 with the combination of cytokines was significantly increased by 24 h. The antiproliferative effect of IFN-gamma alone and that of IFN-gamma and TNF-alpha in combination were blocked completely using an antibody to the IFN-gamma receptor. A hypothesized mechanism of tissue damage in autoimmune inflammatory disorders is via up-regulation of cell surface markers such as intercellular adhesion molecule type I (ICAM-1) and histocompatibility antigen HLA-DR which can exacerbate the inflammatory process. Treatment of HSG cells with IFN-gamma, with or without TNF-alpha, resulted in increased levels of ICAM-1 and the acquisition of HLA-DR expression. These aggregate data suggest that IFN-gamma alone can regulate the expression of cell surface markers involved in the inflammatory process as well as cause a potent yet reversible inhibition of HSG cell growth that is modulated by the presence of TNF-alpha. (C) 1994 Wiley-Liss, Inc. RP WU, AJ (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892, USA. NR 49 TC 46 Z9 46 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 NOV PY 1994 VL 161 IS 2 BP 217 EP 226 DI 10.1002/jcp.1041610205 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA QF854 UT WOS:A1994QF85400004 PM 7962105 ER PT J AU KUZUYA, M KINSELLA, JL AF KUZUYA, M KINSELLA, JL TI REORGANIZATION OF ENDOTHELIAL CORD-LIKE STRUCTURES ON BASEMENT-MEMBRANE COMPLEX (MATRIGEL) - INVOLVEMENT OF TRANSFORMING GROWTH-FACTOR-BETA-1 SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID CAPILLARY-LIKE STRUCTURES; DEPENDENT PROTEIN-KINASE; SMOOTH-MUSCLE CELLS; EXTRACELLULAR-MATRIX; PHENOTYPIC MODULATION; ANGIOGENESIS INVITRO; SELECTIVE INHIBITOR; BIOLOGICAL-ACTIVITY; GENE-EXPRESSION; VASCULAR CELLS AB The formation of capillary-like network structures by cultured vascular endothelial cells on reconstituted basement membrane matrix, Matrigel, models endothelial cell differentiation, the final step of angiogenesis (Kubota et al., 1988; Grant et al., 1989). When endothelial cells derived from bovine aorta and brain capillaries were plated on Matrigel, DNA synthesis was suppressed and a network oi capillary-like structures rapidly formed in 8-12 h. With time, the network broke down, resulting in dense cellular cords radiating from multiple cellular clusters in 16-24 h. Finally, multicellular aggregates of cells were formed as the network underwent further retraction. Network regression was prevented when either dithiothreitol (DTT) or anti-TGF-beta 1 antibodies were added during the assay. The addition of exogenous TCF-beta 1 promoted the regression of endothelial cells into the clusters. This response to TGF-beta 1 was blocked by potent serine threonine protein kinase inhibitors, H-7 and HA100. TGF-beta 1 was released from polymerized Matrigel by incubation with Dulbecco's modified eagle's medium (DMEM) in the absence of cells. The Matrigel-conditioned DMEM inhibited endothelial DNA synthesis even in the presence of anti-TCF-beta 1 antibodies. These results suggest that TGF-beta 1 and possibly other soluble factors from Matrigel may be important for differentiation and remodeling of endothelial cells in a capillary network with possible implications for wound healing and development. (C) 1994 Wiley-Liss, Inc. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. RI Kuzuya, Masafumi/I-1583-2012 NR 68 TC 33 Z9 33 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD NOV PY 1994 VL 161 IS 2 BP 267 EP 276 DI 10.1002/jcp.1041610211 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA QF854 UT WOS:A1994QF85400010 PM 7962111 ER PT J AU NAVERI, L STROMBERG, C SAAVEDRA, JM AF NAVERI, L STROMBERG, C SAAVEDRA, JM TI ANGIOTENSIN-IV REVERSES THE ACUTE CEREBRAL BLOOD-FLOW REDUCTION AFTER EXPERIMENTAL SUBARACHNOID HEMORRHAGE IN THE RAT SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE ANGIOTENSIN IV; CEREBRAL BLOOD FLOW; SUBARACHNOID HEMORRHAGE; NITRIC OXIDE SYNTHASE; CEREBRAL ARTERIES ID RELAXING FACTOR; METABOLISM; BINDING; BRAIN; AUTOREGULATION; IMPAIRMENT; VASOSPASM; ARTERIES; RECEPTOR; RELEASE AB The effect of angiotensin (ANG) IV on CBF after experimental subarachnoid hemorrhage (SAH) was studied in rats using laser-Doppler flowmetry. ANG IV (1 mu g/kg/min i.v.) or saline treatments were started 20 min after SAH. ANG IV increased CBF (from 45 to 84% of baseline) by 60 min. In the saline group, CBF remained low (51%). Pretreatment with the specific ANG II antagonist Sar(1), Ile(8)-ANG II did not antagonize ANG IV. Determination of nitric oxide synthase (NOS) activity in vitro or inhibition of NOS in vivo did not support a role for NO in the action of ANG IV. C1 NIMH,CLIN SCI LAB,PHARMACOL SECT,BETHESDA,MD 20892. NR 22 TC 42 Z9 43 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD NOV PY 1994 VL 14 IS 6 BP 1096 EP 1099 PG 4 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA PM721 UT WOS:A1994PM72100025 PM 7523429 ER PT J AU LUNN, G SANSONE, EB AF LUNN, G SANSONE, EB TI SAFE DISPOSAL OF HIGHLY REACTIVE CHEMICALS SO JOURNAL OF CHEMICAL EDUCATION LA English DT Article C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,ENVIRONM CONTROL & RES PROGRAM,FREDERICK,MD 21702. NR 17 TC 6 Z9 6 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0021-9584 J9 J CHEM EDUC JI J. Chem. Educ. PD NOV PY 1994 VL 71 IS 11 BP 972 EP 976 PG 5 WC Chemistry, Multidisciplinary; Education, Scientific Disciplines SC Chemistry; Education & Educational Research GA PQ937 UT WOS:A1994PQ93700032 ER PT J AU WANG, SM MILNE, GWA KLOPMAN, G AF WANG, SM MILNE, GWA KLOPMAN, G TI GRAPH-THEORY AND GROUP CONTRIBUTIONS IN THE ESTIMATION OF BOILING POINTS SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Article ID PARTITION-COEFFICIENTS; MOLECULAR GRAPHS; AQUEOUS SOLUBILITY; ORGANIC-MOLECULES; HYDROCARBONS; CONNECTIVITY; SERIES; SYSTEM; STATE AB Estimation of normal boiling points of organic compounds using a group contribution method is known to be unsatisfactory and an attempt has been made to improve the accuracy of the estimations by including chemical graph information in the regressions. This leads to a measurable improvement in the results obtained for both a set of 63 alcohols and also a set of 541 structurally diverse organic compounds. This new approach was found to have better predictive ability than the group contribution approach both in the cross-validation tests and in predicting the normal boiling points for 32 new compounds. C1 NCI,DIV CANC TREATMENT,MED CHEM LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. CASE WESTERN RESERVE UNIV,DEPT CHEM,CLEVELAND,OH 44106. NR 31 TC 15 Z9 16 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD NOV-DEC PY 1994 VL 34 IS 6 BP 1242 EP 1250 DI 10.1021/ci00022a004 PG 9 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA PT759 UT WOS:A1994PT75900004 PM 7989396 ER PT J AU SCHMIDT, PJ PURDY, RH MOORE, PH PAUL, SM RUBINOW, DR AF SCHMIDT, PJ PURDY, RH MOORE, PH PAUL, SM RUBINOW, DR TI CIRCULATING LEVELS OF ANXIOLYTIC STEROIDS IN THE LUTEAL-PHASE IN WOMEN WITH PREMENSTRUAL-SYNDROME AND IN CONTROL SUBJECTS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MENSTRUAL-CYCLE; LACTATE INFUSION; PANIC ATTACKS; DOUBLE-BLIND; MOOD; ALPRAZOLAM; DISORDER; PROVOCATION; DYSPHORIA; HORMONES AB The levels of 3 alpha-hydroxy-5 alpha-pregnan-20-one(allopregnanolone) and the epimeric 3 alpha-hydroxy-5 beta-pregnan-20-one(pregnanolone) were studied in women with prospectively confirmed premenstrual syndrome (n = 15) and in a group of asymptomatic control women (n = 12) during the luteal phase of the menstrual cycle. Single late luteal phase plasma samples were selected to make comparisons of plasma hormone levels between patients and controls in the following measures: allopregnanolone, pregnanolone, the ratio of allopregnanolone to pregnanolone, the ratio for each of these anxiolytic steroids to the parent compound progesterone, and the ratio of the sum of allopregnanolone and pregnanolone to progesterone. Differences in these measures were compared by analysis of variance. Additionally, correlations were performed among the various hormone measures and between the hormone measures and the symptom self-ratings. Analysis of variance showed no significant between group differences in the plasma levels of allopregnanolone, pregnanolone, and progesterone. Plasma levels of both allopregnanolone and pregnanolone were correlated with plasma progesterone levels. However, there were no significant correlations between the severity of mood and behavioral symptoms and plasma levels of progesterone, allopregnanolone, and pregnanolone. These data suggest that symptoms of premenstrual syndrome are not associated with a simple deficiency state of either progesterone or its anxiolytic steroid metabolites. C1 NIMH, BEHAV ENDOCRINOL SECT, BETHESDA, MD 20892 USA. NR 20 TC 129 Z9 131 U1 2 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1994 VL 79 IS 5 BP 1256 EP 1260 DI 10.1210/jc.79.5.1256 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PT844 UT WOS:A1994PT84400006 PM 7962316 ER PT J AU WATANABE, RM AZEN, CG ROY, S PERLMAN, JA BERGMAN, RN AF WATANABE, RM AZEN, CG ROY, S PERLMAN, JA BERGMAN, RN TI DEFECTS IN CARBOHYDRATE-METABOLISM IN ORAL-CONTRACEPTIVE USERS WITHOUT APPARENT METABOLIC RISK-FACTORS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; INSULIN SENSITIVITY; MINIMAL-MODEL; QUANTITATIVE ESTIMATION; INTRAVENOUS GLUCOSE; NORMAL WOMEN; SECRETION; AGENTS AB We performed oral glucose tolerance tests and frequently sampled iv glucose tolerance tests in a cross-sectional sample of women taking monophasic norgestrel containing oral contraceptives (OC). The goal of the study was to quantify the individual factors that determine glucose tolerance to assess responsibility for the reduced glucose tolerance associated with the use of OCs. Subjects were selected using stringent criteria to exclude confounding effects of ethnicity, adiposity, or conditions that may predispose subjects to metabolic disorders. Users of the low dose OC (Lo/Ovral and Nordette) and high dose OC (Ovral) were compared to controls, who were required to never have used OCs or to have discontinued OC use for at least 24 months. Oral glucose tolerance tests results confirmed the development of impaired glucose tolerance in both pill groups. Frequently sampled iv glucose tolerance test data were analyzed using the minimal model method to estimate parameters of insulin sensitivity, glucose effectiveness (S-G), and beta-cell function. Lo/Ovral users had lower insulin sensitivity and S-G compared to controls and inappropriately low beta-cell function in relation to the insulin resistance. Ovral users had metabolic parameters that were not different from controls. Based upon comparisons between normal and impaired glucose tolerant subjects combined with stepwise regression analysis, we conclude that Lo/Ovral use results in insulin and glucose resistance, which is not compensated by increased beta-cell function. The reduced glucose tolerance is due primarily to the defect in S-G, and these OC users may place themselves at higher risk for the development of diabetes or cardiovascular disease. The reduced tolerance in Ovral users cannot be explained by the parameters measured in this study. We speculate that these latter subjects represent a special self-selected population in which tolerance is regulated by other factors. Ovral appears to be well tolerated by these women. C1 UNIV SO CALIF, SCH MED, DEPT PHYSIOL & BIOPHYS, METAB RES UNIT, LOS ANGELES, CA 90033 USA. UNIV SO CALIF, SCH MED, DEPT EXERCISE SCI, METAB RES UNIT, LOS ANGELES, CA 90033 USA. UNIV SO CALIF, SCH MED, DEPT OBSTET & GYNECOL, LOS ANGELES, CA 90033 USA. NICHHD, POPULAT RES CTR, CONTRACEPT EVALUAT BRANCH, BETHESDA, MD 20892 USA. FU NIA NIH HHS [2 T32-AG-00093]; NICHD NIH HHS [N01-HD-52906]; NIDDK NIH HHS [DK-29867] NR 20 TC 45 Z9 46 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1994 VL 79 IS 5 BP 1277 EP 1283 DI 10.1210/jc.79.5.1277 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PT844 UT WOS:A1994PT84400010 PM 7962320 ER PT J AU NELSON, LM ANASTI, JN KIMZEY, LM DEFENSOR, RA LIPETZ, KJ WHITE, BJ SHAWKER, TH MERINO, MJ AF NELSON, LM ANASTI, JN KIMZEY, LM DEFENSOR, RA LIPETZ, KJ WHITE, BJ SHAWKER, TH MERINO, MJ TI DEVELOPMENT OF LUTEINIZED GRAAFIAN-FOLLICLES IN PATIENTS WITH KARYOTYPICALLY NORMAL SPONTANEOUS PREMATURE OVARIAN FAILURE SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MENSTRUAL-CYCLE; PREGNANCY AB Despite having amenorrhea and markedly elevated serum gonadotropin levels, some women with karyotypically normal spontaneous premature ovarian failure, nevertheless, have ovarian follicles that function intermittently. Graafian follicles capable of responding to these high FSH levels are faced with high serum LH levels as well, which might induce inappropriate luteinization and prevent normal follicle function. We examined this possibility using weekly blood sampling and sonography in 65 patients. Nearly 50% of our patients demonstrated ovarian follicle function [serum estradiol, >183 pmol/L (50 pg/mL)] during a median of 4 months of observation (range, 2-6 months). However, during this observation, only 16% achieved an ovulatory serum progesterone level [>9.5 nmol/L (3.0 ng/mL)]. We imaged an antral follicle by sonography in over 40% of patients (27 of 65), and serum estradiol was significantly greater when an antral follicle was present. The follicles in these patients were not functioning normally, however. In contrast to normal women, patients with ovarian failure had poor correlation between follicle diameter and serum estradiol. We biopsied these antral follicles in 6 patients and found luteinized Graafian follicles in all cases. Therefore, luteinized Graafian follicles account for at least 60% of the antral structures imaged (95% confidence limit). Thus, inappropriate luteinization of Graafian follicles appears to be a major pathophysiological mechanism in patients with karyotypically normal spontaneous premature ovarian failure. C1 NIH, CTR CLIN, DEPT NURSING, BETHESDA, MD 20892 USA. NIDDK, BIOL CHEM LAB, BETHESDA, MD 20892 USA. NIH, CTR CLIN, DEPT DIAGNOST RADIOL, BETHESDA, MD 20892 USA. NCI, PATHOL LAB, BETHESDA, MD 20892 USA. RP NELSON, LM (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, GYNECOL RES SECT, BLDG 10, ROOM 10N262, BETHESDA, MD 20892 USA. NR 25 TC 96 Z9 100 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1994 VL 79 IS 5 BP 1470 EP 1475 DI 10.1210/jc.79.5.1470 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PT844 UT WOS:A1994PT84400042 PM 7962345 ER PT J AU CARRINGTON, M KRUEGER, LJ HOLSCLAW, DS IANNUZZI, MC DEAN, M MANN, D AF CARRINGTON, M KRUEGER, LJ HOLSCLAW, DS IANNUZZI, MC DEAN, M MANN, D TI CYSTIC FIBROSIS-RELATED DIABETES IS ASSOCIATED WITH HLA DQB1 ALLELES ENCODING ASP-57(-) MOLECULES SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE MAJOR HISTOCOMPATIBILITY COMPLEX; INSULIN DEPENDENT DIABETES MELLITUS; CYSTIC FIBROSIS; PANCREATIC INSUFFICIENCY ID CONFERS SUSCEPTIBILITY; MELLITUS; GENE; MUTATIONS; DISEASE; IDENTIFICATION; ANTIGENS AB The incidence of insulin-dependent diabetes in individuals with cystic fibrosis is nearly 100 times greater than in the general population. In the latter group, strong associations with specific HLA DQA1 and DQB1 alleles have been observed. To determine if a similar distribution of alleles occurs in cystic fibrosis patients with diabetes, a cohort of these individuals was typed for DQA1 and DQB1 alleles. HLA DQB1*0201 (Asp57(-)) was more frequent in diabetics compared to controls (40.4 vs 28%), while the frequency of alleles encoding Asp57(+) molecules was lower in diabetics relative to both the cystic fibrosis-only controls (P = 0.025) and the general population (P = 0.008). The presence of at least one protective DQA1-DQB1 heterodimer (i.e., Arg52(-) and Asp57(+), respectively) in cis or trans was significantly lower in the diabetics than in either of the control groups. Thus, the HLA alleles known to be associated with insulin-dependent diabetes mellitus in the general population are also found in diabetics with cystic fibrosis. C1 HAHNEMANN UNIV,DEPT PEDIAT,PHILADELPHIA,PA 19102. HENRY FORD HOSP,DETROIT,MI 48202. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. RP CARRINGTON, M (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,POB B,FREDERICK,MD 21702, USA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 36 TC 11 Z9 11 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD NOV PY 1994 VL 14 IS 6 BP 353 EP 358 DI 10.1007/BF01546319 PG 6 WC Immunology SC Immunology GA PW795 UT WOS:A1994PW79500003 PM 7883862 ER PT J AU SNELLER, MC EISENSTEIN, EM BASELER, M LANE, HC DONOGHUE, ET FALLOON, J AF SNELLER, MC EISENSTEIN, EM BASELER, M LANE, HC DONOGHUE, ET FALLOON, J TI A UNIQUE SYNDROME OF IMMUNODEFICIENCY AND AUTOIMMUNITY ASSOCIATED WITH ABSENT T-CELL CD2 EXPRESSION SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE CD2; IMMUNODEFICIENCY; AUTOIMMUNITY; T CELLS; ANTIGEN PRESENTING CELLS; T CELL RECEPTOR ID HUMAN PERIPHERAL-BLOOD; MONOCLONAL-ANTIBODIES; FAS ANTIGEN; FUNCTIONAL-CHARACTERIZATION; HUMAN-LYMPHOCYTES; SURFACE-ANTIGENS; TRANSGENIC MICE; LFA-3 ANTIGENS; RECEPTOR; PROTEIN AB CD2 is a glycoprotein expressed on the surface of human T cells that mediates adhesion between T cells and antigen presenting cells. CD2 also functions in concert with the T cell receptor to transduce signals that lead to T cell activation. The CD8 and CD4 molecules are transmembrane glycoproteins that art expressed on mutually exclusive populations of mature T cells and bind to determinants on major histocompatibility complex class I and class II molecules respectively. Like CD2, CD4 and CD8 function to promote adhesion between T cells and antigen presenting cells and potentiate signaling via the T cell receptor. We studied a patient with idiopathic lymphopenia and disseminated infection with Mycobacterium avium. The patient also suffered from recurrent deep venous thrombosis in association with anticardiolipin and anti-DNA antibodies. Peripheral blood T cells from this patient were polyclonal and expressed no detectable CD2 RNA or protein as determined by northern blotting, immunofluorescent staining with anti-CD2 antibodies, and failure to form rosettes with sheep red blood cells. In addition, the majority (85%) of this patient's T cells did not express either CD4 or CD8 but did express the alpha/beta T cell receptor. T cells from this patient failed to respond to stimulation with alloantigen or specific antigen. In contrast, there was a normal response to stimulation with immobilized anti-CD3 antibody. The clinical and immunologic findings in this patient provide in vivo evidence that the accessory molecules CD2, CD4, and CD8 play important roles in the regulation of normal human T cell activation. C1 NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,CLIN IMMUNOL SERV,FREDERICK,MD 21702. RP SNELLER, MC (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 11B-13,BETHESDA,MD 20892, USA. NR 40 TC 4 Z9 4 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD NOV PY 1994 VL 14 IS 6 BP 359 EP 367 DI 10.1007/BF01546320 PG 9 WC Immunology SC Immunology GA PW795 UT WOS:A1994PW79500004 PM 7883863 ER PT J AU DIAMONDSTONE, LS TOLLERUD, DJ FUCHS, D WACHTER, H BROWN, LM MALONEY, E KURMAN, CC NELSON, DL BLATTNER, WA AF DIAMONDSTONE, LS TOLLERUD, DJ FUCHS, D WACHTER, H BROWN, LM MALONEY, E KURMAN, CC NELSON, DL BLATTNER, WA TI FACTORS INFLUENCING SERUM NEOPTERIN AND BETA(2)-MICROGLOBULIN LEVELS IN A HEALTHY DIVERSE POPULATION SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE NEOPTERIN; BETA(2)-MICROGLOBULIN; IMMUNOLOGY; BIOLOGICAL MARKERS ID SOLUBLE INTERLEUKIN-2 RECEPTORS; T-CELL SUBSETS; HIV-1 INFECTION; BETA-2 MICROGLOBULIN; FOLLOW-UP; BETA-2-MICROGLOBULIN; REJECTION; MARKERS; BETA2-MICROGLOBULIN; BIOSYNTHESIS AB Sera and questionnaire data from a population-based random sample of healthy adults was used to evaluate factors influencing neopterin and beta 2-microglobulin (beta 2m) values. Both neopterin and beta 2m levels increased with age and were higher among white than blacks (mean values for whites and blacks: neopterin, 5.06 vs 4.49 nmol/L; beta 2m, 1.36 vs 1.28 mg/L). Gender differences were noted for beta 2m but not neopterin values (beta 2m males vs females: 1.37 vs 1.29 mg/L). Neopterin values were lower among current smokers than among nonsmokers (4.32 vs 5.16 nmol/L) and were higher among users of antihistamines (5.46 among users vs 4.65 nmol/L among nonusers). Neopterin and beta 2m were correlated in this healthy adult population (adjusted r = 0.53, P = 0.001), yet no other interrelationships with numerous biologic markers except between beta 2m and serum-soluble interleukin-2 receptor levels (adjusted r = .41, P = 0.05) were observed. These findings provide important baseline information to consider before planning or evaluating studies utilizing neopterin or beta 2m levels. C1 UNIV PITTSBURGH, GRAD SCH PUBL HLTH, DEPT ENVIRONM & OCCUPAT HLTH, PITTSBURGH, PA 15261 USA. NCI, VIRAL EPIDEMIOL BRANCH, BETHESDA, MD 20852 USA. UNIV INNSBRUCK, INST MED CHEM & BIOCHEM, A-6020 INNSBRUCK, AUSTRIA. NCI, EPIDEMIOL & BIOSTAT PROGRAM, BETHESDA, MD 20852 USA. NCI, METAB BRANCH, BETHESDA, MD 20852 USA. NR 39 TC 55 Z9 56 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD NOV PY 1994 VL 14 IS 6 BP 368 EP 374 DI 10.1007/BF01546321 PG 7 WC Immunology SC Immunology GA PW795 UT WOS:A1994PW79500005 PM 7883864 ER PT J AU SIGOUNAS, G KOLAITIS, N MONELLTORRENS, E NOTKINS, AL AF SIGOUNAS, G KOLAITIS, N MONELLTORRENS, E NOTKINS, AL TI POLYREACTIVE IGM ANTIBODIES IN THE CIRCULATION ARE MASKED BY ANTIGEN-BINDING SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE POLYREACTIVE ANTIBODIES; IGM; ANTIGEN BINDING ID SYSTEMIC LUPUS-ERYTHEMATOSUS; MONOREACTIVE HIGH-AFFINITY; B-CELL REPERTOIRE; MONOCLONAL AUTOANTIBODIES; NATURAL AUTOANTIBODIES; RHEUMATOID-ARTHRITIS; CLONAL ANALYSIS; SELF ANTIGENS; RABIES VIRUS; HUMAN-SERA AB Human plasma containing IgM showed only minimal, if any, reactivity with a panel of antigens as measured by ELISA. In contrast, affinity-purified IgM showed many times more reactivity with the same panel of antigens. When plasma was added back to the affinity-purified IgM, the reactivity of the IgM with antigens was completely inhibited by undiluted plasma and by as much as 40% with as little as a 1:100 dilution of plasma. When the affinity-purified IgM was affinity-purified a second time by passage through antigen-specific columns (e.g., insulin or Fc or beta-galactosidase), the eluted antibodies bound not only to the antigen used for purification, but also to a panel of unrelated antigens, indicating that the antibodies were polyreactive. It is concluded that polyreactive IgM antibodies are present in the circulation but are masked by binding to circulating antigens. RP SIGOUNAS, G (reprint author), NIDR,ORAL MED LAB,BLDG 30,ROOM 227,BETHESDA,MD 20892, USA. NR 27 TC 33 Z9 33 U1 0 U2 5 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD NOV PY 1994 VL 14 IS 6 BP 375 EP 381 DI 10.1007/BF01546322 PG 7 WC Immunology SC Immunology GA PW795 UT WOS:A1994PW79500006 PM 7883865 ER PT J AU BASTA, M DALAKAS, MC AF BASTA, M DALAKAS, MC TI HIGH-DOSE INTRAVENOUS IMMUNOGLOBULIN EXERTS ITS BENEFICIAL EFFECT IN PATIENTS WITH DERMATOMYOSITIS BY BLOCKING ENDOMYSIAL DEPOSITION OF ACTIVATED COMPLEMENT FRAGMENTS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE COMPLEMENT MEMBRANE ATTACK COMPLEX; COMPLEMENT C3B; IMMUNOMODULATION; IMMUNOGLOBULIN THERAPY; AUTOIMMUNE DISEASES ID GAMMA-GLOBULIN THERAPY; MONOCLONAL-ANTIBODIES; IMMUNE-COMPLEXES; POLYMYOSITIS; MYOPATHIES; RECEPTORS; CLEARANCE; DISEASE; INVITRO; DAMAGE AB In patients with dermatomyositis (DM) the earliest lesion is microvasculopathy mediated by deposition of C5b-C9 membranolytic attack complex (MAC) on intramuscular capillaries. This leads sequentially to muscle ischemia, necrosis of muscle fibers, and muscle weakness. High-dose intravenous immunoglobulin (IVIG), which can modulate complement-dependent tissue damage in animal models, has been shown to be effective in the treatment of patients with DM. We used an in vitro C3 uptake assay to examine 55 coded sera from 13 patients with DM and 5 patients with other non-complement-mediated neuromuscular diseases, before and after treatment with IVIG or placebo. Patients with active DM had a significantly higher baseline C3 uptake compared with the others (geometric mean 12,190 vs 3,090 cpm). Post-IVIG but not post-placebo sera inhibited the C3 uptake, without depleting the complement components, by 70.6-93.4%. The maximum inhibition of C3 uptake occurred within hours after IVIG infusion, started to rebound 2 d later, and reached pretreatment levels after 30 d. The serum levels of SC5b-9 complex production were high at baseline but normalized after IVIG therapy. Repeat biopsies from muscles of improved patients showed disappearance of C3b NEO and MAC deposits from the endomysial capillaries and restoration of the capillary network. We conclude that IVIG exerts its beneficial clinical effect by intercepting the assembly and deposition of MAC on the endomysial capillaries through the formation of complexes between the infused immunoglobulins and C3b, thereby preventing the incorporation of activated C3 molecules into C5 convertase. These findings provide the first serological and in situ evidence that IVIG modulates complement attack in a human disease. C1 NINCDS,MED NEUROL BRANCH,BETHESDA,MD 20892. RP BASTA, M (reprint author), NIAID,CLIN INVEST LAB,BLDG 10, RM 11N238,BETHESDA,MD 20892, USA. OI Basta, Milan/0000-0001-5958-9241 NR 34 TC 252 Z9 257 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 NOV PY 1994 VL 94 IS 5 BP 1729 EP 1735 DI 10.1172/JCI117520 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PQ941 UT WOS:A1994PQ94100005 PM 7962520 ER PT J AU ENSOLI, B MARKHAM, P KAO, V BARILLARI, G FIORELLI, V GENDELMAN, R RAFFELD, M ZON, G GALLO, RC AF ENSOLI, B MARKHAM, P KAO, V BARILLARI, G FIORELLI, V GENDELMAN, R RAFFELD, M ZON, G GALLO, RC TI BLOCK OF AIDS-KAPOSIS SARCOMA (KS) CELL-GROWTH, ANGIOGENESIS, AND LESION FORMATION IN NUDE-MICE BY ANTISENSE OLIGONUCLEOTIDE TARGETING BASIC FIBROBLAST GROWTH-FACTOR - A NOVEL STRATEGY FOR THE THERAPY OF KS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE ENDOTHELIAL CELLS; CELL INVASION; CELL CYCLE ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; ENDOTHELIAL-CELLS; GENE-EXPRESSION; TAT PROTEIN; OLIGODEOXYNUCLEOTIDES; INTERFERON; CYTOKINES; INVITRO AB Kaposi's sarcoma (KS) is the most frequent tumor of HIV-infected individuals (AIDS-KS). Typical features of KS are proliferating spindle-shaped cells, considered to be the tumor cells of KS, and endothelial cells forming blood vessels. Basic fibroblast growth factor (bFGF), a potent angiogenic factor, is highly expressed by KS spindle cells in vivo and after injection in nude mice it induces vascular lesions closely resembling early KS in humans. Similar lesions are induced by inoculating nude mice with cultured spindle cells from AIDS-KS lesions (AIDS-KS cells) which produce and release bFGF. Here we show that phosphorothioate antisense (AS) oligonucleotides directed against bFGF mRNA (ASbFGF) inhibit both the growth of AIDS-KS cells derived from different patients and the angiogenic activity associated with these cells, including the induction of KS-like lesions in nude mice. These effects are due to the block of the production of bFGF which is required by AIDS-KS cells to enter the cell cycle and which, after release, mediates angiogenesis. The effects of ASbFGF are specific, dose dependent, achieved at low (0.1-1 mu M), nontoxic, oligomer concentrations, and are reversed by the addition of bFGF to the cells, suggesting that ASbFGF oligomers are promising drug candidates for KS therapy. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. ADV BIOSCI LABS INC,KENSINGTON,MD 20895. LYNX THERAPEUT INC,HAYWARD,CA 94545. RP ENSOLI, B (reprint author), NCI,TUMOR CELL BIOL LAB,BLDG 37,RM 6A09,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 40 TC 120 Z9 121 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 NOV PY 1994 VL 94 IS 5 BP 1736 EP 1746 DI 10.1172/JCI117521 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PQ941 UT WOS:A1994PQ94100006 PM 7525646 ER PT J AU GRESSENS, P HILL, JM PAINDAVEINE, B GOZES, I FRIDKIN, M BRENNEMAN, DE AF GRESSENS, P HILL, JM PAINDAVEINE, B GOZES, I FRIDKIN, M BRENNEMAN, DE TI SEVERE MICROCEPHALY INDUCED BY BLOCKADE OF VASOACTIVE-INTESTINAL-PEPTIDE FUNCTION IN THE PRIMITIVE NEUROEPITHELIUM OF THE MOUSE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE MITOSIS; GROWTH RETARDATION; EMBRYO GROWTH FACTOR; VASOACTIVE INTESTINAL PEPTIDE ANTAGONIST ID CYCLASE-ACTIVATING POLYPEPTIDE; CENTRAL-NERVOUS-SYSTEM; RECEPTOR; ANTAGONIST; RAT; EXPRESSION; GROWTH; MICE; METHYLAZOXYMETHANOL; SURVIVAL AB Vasoactive intestinal peptide (VIP) has potent growth-related actions that influence cell mitosis, neuronal survival, and neurodifferentiation in cell culture. VIP can also produce dramatic growth in postimplantation mouse embryos in vitro, characterized by large increases in cell number. The goal of the present study was to assess the role of VIP on early nervous system development in vivo. Pregnant mice were treated with a specific antagonist to VIP. Prenatal administration of the antagonist early in development (E9-E11) produced severe microcephaly characterized by decreased embryonic brain weight with reduced DNA and protein content. The retardation of growth was disproportionally manifested in the brain compared with the body and was prevented by co-treatment with VIP. Identical treatment with the antagonist later in gestation had no detectable effect on embryonic growth. VIP receptors, which were restricted to the central nervous system during this stage of embryonic development, were increased in the neuroepithelium of antagonist-treated embryos while the number of cells in S-phase was significantly decreased. Thus, VIP regulates brain growth in vivo and inhibition of its action provides new insight into a molecular mechanism for microcephaly. C1 NICHHD,DEV & MOLEC PHARMACOL SECT,DEV NEUROBIOL LAB,BETHESDA,MD 20892. NINCDS,EXPTL NEUROPATHOL LAB,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. UNIV CATHOLIQUE LOUVAIN,SCH MED,SERV PEDIAT,BRUSSELS,BELGIUM. TEL AVIV UNIV,DEPT CHEM PATHOL,IL-69978 TEL AVIV,ISRAEL. WEIZMANN INST SCI,DEPT ORGAN CHEM,IL-76100 REHOVOT,ISRAEL. NR 39 TC 104 Z9 105 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 1994 VL 94 IS 5 BP 2020 EP 2027 DI 10.1172/JCI117555 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PQ941 UT WOS:A1994PQ94100040 PM 7962548 ER PT J AU XIAO, RP SPURGEON, HA OCONNOR, F LAKATTA, EG AF XIAO, RP SPURGEON, HA OCONNOR, F LAKATTA, EG TI AGE-ASSOCIATED CHANGES IN BETA-ADRENERGIC MODULATION ON RAT CARDIAC EXCITATION-CONTRACTION COUPLING SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE AGING; BETA-ADRENERGIC RECEPTOR; CALCIUM CURRENT; CYTOSOLIC CALCIUM; CONTRACTION ID SARCOPLASMIC-RETICULUM; VENTRICULAR MYOCYTES; CALCIUM CHANNELS; PURKINJE-CELL; HEART-MUSCLE; STIMULATION; MYOCARDIUM; SENESCENCE; RELEASE; CA2+ AB Previous studies have demonstrated that the ability of beta-adrenergic receptor (beta AR) stimulation to increase cardiac contractility declines with aging. In the present study, the control mechanisms of excitation-contraction (EC) coupling, including calcium current (I-Ca), cytosolic Ca2+ (Ca-i(2+)) transient and contraction in response to beta AR stimulation were investigated in ventricular myocytes isolated from rat hearts of a broad age range (2, 6-8, and 24 mo). While the baseline contractile performance and the Ca-i(2+) transient did not differ markedly among cells from hearts of all age groups, the responses of the Ca-i(2+) transient and contraction to beta-adrenergic stimulation by norepinephrine (NE) diminished with aging: the threshold concentration and the ED(50) increased in rank order with aging; the maximum responses of contraction and Ca-i(2+) transient decreased with aging. Furthermore, the efficacy of beta AR stimulation to increase I-Ca, was significantly reduced with aging, and the diminished responses of the contraction and Ca-i(2+) transient amplitudes to NE were proportional to the reductions in the I-Ca, response. These findings suggest that the observed age-associated reduction in beta AR modulation of the cardiac contraction is, in part at least, due to a deficit in modulation of Ca-i(2+), particularly the activity of L-type calcium channels. C1 NIA, GERONTOL RES CTR, CARDIOVASC SCI LAB, BALTIMORE, MD 21224 USA. NR 34 TC 77 Z9 80 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 1994 VL 94 IS 5 BP 2051 EP 2059 DI 10.1172/JCI117559 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PQ941 UT WOS:A1994PQ94100044 PM 7962551 ER PT J AU KELLEY, MJ MULSHINE, JL AF KELLEY, MJ MULSHINE, JL TI ANTICANCER ANTIBODIES FOR LUNG-CANCER SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter RP KELLEY, MJ (reprint author), NCI,BETHESDA,MD 20892, USA. OI Kelley, Michael/0000-0001-9523-6080 NR 3 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1994 VL 12 IS 11 BP 2519 EP 2520 PG 2 WC Oncology SC Oncology GA PP880 UT WOS:A1994PP88000045 PM 7818695 ER PT J AU PETRALIA, RS WANG, YX WENTHOLD, RJ AF PETRALIA, RS WANG, YX WENTHOLD, RJ TI HISTOLOGICAL AND ULTRASTRUCTURAL-LOCALIZATION OF THE KAINATE RECEPTOR SUBUNITS, KA2 AND GLUR6/7, IN THE RAT NERVOUS-SYSTEM USING SELECTIVE ANTIPEPTIDE ANTIBODIES SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE EXCITATORY AMINO ACIDS; ULTRASTRUCTURE; IMMUNOCYTOCHEMISTRY; AMPA; NMDA; GLUR7 ID ACID BINDING-SITES; HIGH-AFFINITY KAINATE; CULTURED HIPPOCAMPAL-NEURONS; DEPENDENT PROTEIN-KINASE; D-ASPARTATE RECEPTORS; GLUTAMATE-RECEPTOR; AUTORADIOGRAPHIC LOCALIZATION; MESSENGER-RNAS; SPINAL-CORD; IMMUNOCYTOCHEMICAL LOCALIZATION AB Kainate receptors are found throughout many regions of the brain and presumably contribute to responses of neurons to glutamate and other excitatory amino acids. Two affinity-purified polyclonal antibodies that recognize the kainate binding subunits, KA2 and GluR6, were made using C-terminus peptides. A previous study demonstrated that each antibody is specific for its subunit, although antibody to GluR6 recognizes GluR7 to some extent (hence the designation GluR6/7). Vibratome sections immunostained with either antibody showed light to moderate staining in many structures in the brain as well as in cervical spinal cord, dorsal root and vestibular ganglia, and pineal and pituitary glands. Moderate levels were seen in the olfactory bulb, cerebral cortex, caudate/putamen, and hypothalamus, whereas much of the thalamus was stained lightly. In the hippocampus, CA3 pyramidal cells were stained more densely than CAI pyramidal cells-the difference more evident with antibody to GluR6/7. In addition, neuropilar staining was densest in the stratum lucidum of the CA3 region. In the brainstem, staining was moderate to moderately dense in a number of sensory, motor, and reticular nuclei. The moderately dense staining in the reticulothalamic nucleus and pontine nuclei with antibody to GluR6/7 may represent its recognition of GluR7. In the cerebellum, staining was moderate in granular and molecular layers with antibody to KA2 and in the molecular layer with antibody to GluR6/7, whereas it was moderately dense to dense in the granular layer with the GluR6/7 antibody. Outside of the brain, densest staining nas seen with antibody to KA2 in the intermediate lobe of the pituitary gland. Ultrastructural localization of immunostaining was examined in the hippocampus, cerebral cortex, and cerebellar cortex. Typically, major staining was in postsynaptic densities apposed by unstained presynaptic terminals with round or mainly round vesicles and in associated dendrites. The light microscope pattern of staining was fairly similar to that of previous [H-3]kainate binding and in situ hybridization studies. In addition, comparison with previous studies on distribution of other types of glutamate receptors indicates that KA2 and GluR6/7 are found with various other subunits in many of the same cell populations throughout the nervous system. (C) 1994 Wiley-liss, Inc. RP PETRALIA, RS (reprint author), NIDCD,NEUROCHEM LAB,BLDG 36,ROOM 5D-08,BETHESDA,MD 20892, USA. NR 88 TC 256 Z9 257 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 NOV 1 PY 1994 VL 349 IS 1 BP 85 EP 110 DI 10.1002/cne.903490107 PG 26 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA PM876 UT WOS:A1994PM87600006 PM 7852627 ER PT J AU BERNSTEIN, EF HARISIADIS, L SALOMON, GD HARRINGTON, F MITCHELL, JB UITTO, J GLATSTEIN, E RUSSO, A AF BERNSTEIN, EF HARISIADIS, L SALOMON, GD HARRINGTON, F MITCHELL, JB UITTO, J GLATSTEIN, E RUSSO, A TI HEALING IMPAIRMENT OF OPEN WOUNDS BY SKIN IRRADIATION SO JOURNAL OF DERMATOLOGIC SURGERY AND ONCOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; GENE-EXPRESSION; MOUSE SKIN; FACTOR-BB; MODEL; ADRIAMYCIN; REVERSAL; COLLAGEN; CONTRACTION; STRENGTH AB BACKGROUND. Ionizing radiation is frequently used for the treatment of malignancy. Sequelae of therapeutic radiation frequently present clinical problems in the form of poor wound healing and easy injury of treated tissue in response to mild trauma. OBJECTIVE. We describe a radiation-impaired wound healing model in guinea pigs, developed to determine the effect of cutaneous irradiation on wound contraction. METHODS. Guinea pigs were anesthetized and a flap of skin was isolated and treated with x-rays to 18 Gy. Circular wounds of identical size were made in irradiated and control skin, and average wound size was recorded. Results. Our results demonstrate that a statistically significant wound healing deficit is produced in open wounds by surface irradiation of skin. CONCLUSION. Radiation of skin results in slower healing of open wounds, and provides an in vivo system for evaluation of topical dressings and growth factors in radiation-impaired wounds. C1 UNIV TEXAS,SW MED SCH,DEPT RADIAT ONCOL,DALLAS,TX 75230. NIH,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,MED CTR,RADIAT THERAPY SECT,WASHINGTON,DC 20037. RP BERNSTEIN, EF (reprint author), THOMAS JEFFERSON UNIV,DEPT DERMATOL,233 S 10TH ST,SUITE 450,PHILADELPHIA,PA 19107, USA. NR 32 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0148-0812 J9 J DERMATOL SURG ONC PD NOV PY 1994 VL 20 IS 11 BP 757 EP 760 PG 4 WC Oncology; Dermatology; Surgery SC Oncology; Dermatology; Surgery GA PT234 UT WOS:A1994PT23400011 PM 7962938 ER PT J AU PIMENTA, PF TOURAY, M MILLER, L AF PIMENTA, PF TOURAY, M MILLER, L TI THE JOURNEY OF MALARIA SPOROZOITES IN THE MOSQUITO SALIVARY-GLAND SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article DE AEDES AEGYPTI; INVASION; PLASMODIUM GALLINACEUM; ULTRASTRUCTURE ID PLASMODIUM-FALCIPARUM SPOROZOITES; ANOPHELES-STEPHENSI; CIRCUMSPOROZOITE PROTEIN; TOXOPLASMA-GONDII; AEDES-AEGYPTI; ELECTRON-MICROSCOPE; HOST-CELLS; MEMBRANE; INVASION; MITOCHONDRIA AB The Life cycle of malaria parasites in the mosquito vector is completed when the sporozoites infect the salivary gland and are ready to be injected into the vertebrate host. This paper describes the fine structure of the invasive process of mosquito salivary glands by malaria parasites. Plasmodium gallinaceum sporozoites start the invasion process by attaching to and crossing the basal lamina and then penetrating the host plasma membrane of the salivary cells. The penetration process appears to involve the formation of membrane junctions. Once inside the host cells, the sporozoites are seen within vacuoles attached by their anterior end to the vacuolar membrane. Mitochondria surround, and are closely associated with, the invading sporozoites. After the disruption of the membrane vacuole, the parasites traverse the cytoplasm, attach to, and invade the secretory cavity through the apical plasma membrane of the cells. Inside the secretory cavity, sporozoites are seen again inside vacuoles. Upon escaping from these vacuoles, sporozoites are positioned in parallel arrays forming large bundles attached by multilammelar membrane junctions. Several sporozoites are seen around and inside the secretory duct. Except for the penetration of the chitinous salivary duct, our observations have morphologically characterized the entire process of sporozoite passage through the salivary gland. C1 NIAID,MALARIA RES LAB,BETHESDA,MD 20892. RP PIMENTA, PF (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. NR 27 TC 74 Z9 76 U1 1 U2 9 PU SOC PROTOZOOLOGISTS PI POTOMAC PA 12263 GREENLEAF AVE, POTOMAC, MD 20854 SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD NOV-DEC PY 1994 VL 41 IS 6 BP 608 EP 624 DI 10.1111/j.1550-7408.1994.tb01523.x PG 17 WC Microbiology SC Microbiology GA QD425 UT WOS:A1994QD42500012 PM 7866385 ER PT J AU UHL, GR JOHNSON, PS AF UHL, GR JOHNSON, PS TI NEUROTRANSMITTER TRANSPORTERS - 3 IMPORTANT GENE FAMILIES FOR NEURONAL FUNCTION SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE COCAINE; PARKINSONS DISEASE; SYMPORTERS; ANTIPORTERS ID MONOAMINE TRANSPORTER; GLUTAMATE TRANSPORTER; TAQI RFLPS; RAT-BRAIN; EXPRESSION; COCAINE; CLONING; NEUROTOXIN; BINDING AB Three distinct gene families encode transporter proteins that aid in temporal and spatial buffering of neurotransmitter and neurotransmitter metabolite concentrations and allow neurons to cycle and recycle transmitter molecules. Analyses of these gene families and their products are likely to enhance understanding of the molecular neurobiology of neuronal function and may elucidate contributors to the genetic etiologies of neurological and psychiatric disease. C1 NIDA,INTRAMURAL RES PROGRAM,OFF DIRECTOR,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. RP UHL, GR (reprint author), NIDA,ADDICT RES CTR,INTRAMURAL RES PROGRAM,MOLEC NEUROBIOL BRANCH,BOX 5180,BALTIMORE,MD 21224, USA. NR 32 TC 109 Z9 109 U1 2 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD NOV PY 1994 VL 196 BP 229 EP 236 PG 8 WC Biology SC Life Sciences & Biomedicine - Other Topics GA PW454 UT WOS:A1994PW45400018 PM 7823024 ER PT J AU WAHL, SM AF WAHL, SM TI TRANSFORMING GROWTH-FACTOR-BETA - THE GOOD, THE BAD, AND THE UGLY SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Editorial Material ID NITRIC-OXIDE SYNTHASE; TGF-BETA; SYNOVIAL INFLAMMATION; EXPRESSION; SUPPRESSION; MECHANISMS; MONOCYTES; ARTHRITIS; DISEASE; CELLS RP WAHL, SM (reprint author), NIDR,IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 35 TC 390 Z9 402 U1 0 U2 2 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 NOV 1 PY 1994 VL 180 IS 5 BP 1587 EP 1590 DI 10.1084/jem.180.5.1587 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PP543 UT WOS:A1994PP54300002 PM 7964446 ER PT J AU CASSELL, DJ SCHWARTZ, RH AF CASSELL, DJ SCHWARTZ, RH TI A QUANTITATIVE-ANALYSIS OF ANTIGEN-PRESENTING CELL-FUNCTION - ACTIVATED B-CELLS STIMULATE NAIVE CD4 T-CELLS BUT ARE INFERIOR TO DENDRITIC CELLS IN PROVIDING COSTIMULATION SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MIXED LEUKOCYTE REACTION; TOXIC LYMPHOCYTES-T; DEFICIENT MICE; IMMUNE-RESPONSES; PRIMING INVIVO; LYMPH-NODES; EXPRESSION; INDUCTION; RECEPTOR; INTERLEUKIN-2 AB Ligation of CD28 on CD4 Th1 clones and freshly isolated mixtures of naive and memory CD4 T cells triggered their T cell receptors (TCR) is sufficient to induce the costimulatory signals necessary for interleukin 2 (IL-2) production by these cells. CTLA-4-reactive ligands expressed on antigen-presenting cells (APC) are critical in providing costimulatory signals to these T cell populations. We demonstrate that these activation characteristics apply equally to purified naive CD4 T cells. Because B cell blasts express CTLA-4-reactive ligands and high levels of adhesion and major histocompatibility complex class II molecules, they would be expected to engage both the TCR and CD28 and consequently stimulate IL-2 production by naive CD4 T cells. Using purified populations of cells in limiting dilution cultures, we have carried out a quantitative analysis of the interaction between naive CD4 T cells and either activated B or dendritic cells. We demonstrate that B cell blasts stimulate a high frequency of naive CD4 T cells. Slight differences in TCR signaling efficiency between the two APC types were observed. Even at optimal peptide concentrations, however, the amount of IL-2 made by individual T cells was fourfold lower in response to B cell blasts than to dendritic cells. This relative deficiency of activated B cells was due to their inability to optimally costimulate naive CD4 T cells. C1 NIAID,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 67 TC 126 Z9 126 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 NOV 1 PY 1994 VL 180 IS 5 BP 1829 EP 1840 DI 10.1084/jem.180.5.1829 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PP543 UT WOS:A1994PP54300025 PM 7525839 ER PT J AU INABA, K WITMERPACK, M INABA, M HATHCOCK, KS SAKUTA, H AZUMA, M YAGITA, H OKUMURA, K LINSLEY, PS IKEHARA, S MURAMATSU, S HODES, RJ STEINMAN, RM AF INABA, K WITMERPACK, M INABA, M HATHCOCK, KS SAKUTA, H AZUMA, M YAGITA, H OKUMURA, K LINSLEY, PS IKEHARA, S MURAMATSU, S HODES, RJ STEINMAN, RM TI THE TISSUE DISTRIBUTION OF THE B7-2 COSTIMULATOR IN MICE - ABUNDANT EXPRESSION ON DENDRITIC CELLS IN-SITU AND DURING MATURATION IN-VITRO SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID EPIDERMAL LANGERHANS CELLS; COLONY-STIMULATING FACTOR; CTLA-4 COUNTER-RECEPTOR; LYMPHOCYTES-T; MOUSE SPLEEN; INTERLEUKIN-2 PRODUCTION; ACTIVATION ANTIGEN-B7; MONOCLONAL-ANTIBODY; SURFACE-MOLECULE; 9.3 ANTIGEN AB B7-2 isa recently discovered, second ligand for the CTLA-4/CD28, T cell signaling system. Using the GL-1 rat monoclonal antibody (mAb), we monitored expression of B7-2 on mouse leukocytes with an emphasis on dendritic cells. By cytofluorography, little or no B7-2 was detected on most cell types isolated from spleen, thymus, peritoneal cavity, skin, marrow, and blood. However, expression of B7-2 could be upregulated in culture. In the case of epidermal and spleen dendritic cells, which become highly immunostimulatory for T cells during a short period of culture, the upregulation of B7-2 was dramatic and did not require added stimuli. Lipopolysaccharide did not upregulate B7-2 levels on dendritic cells, in contrast to macrophages and B cells. By indirect immunolabeling, the level of staining with GL-1 mAb exceeded that seen with rat mAbs to several other surface molecules including intercellular adhesion molecule 1, B7-1, CD44, and CD45, as well-as new hamster mAbs to CD40, CD48, and B7-1/CD80. Of these accessory molecules, B7-21 was a major species that increased in culture, implying a key role for B7-2 in the functional maturation of dendritic cells. B7-2 was the main (>90%) CTLA-4 ligand on mouse dendritic cells. When we applied GL-1 to tissue sections of a dozen different organs, clear-cut staining with B7-2 antigen was found in many. B7-2 staining was noted on liver Kupffer cells, interstitial cells of heart and lung, and profiles in the submucosa of the esophagus. B7-2 staining was minimal in the kidney and in the nonlymphoid regions of the gut, and was not observed at all in the brain. In the tongue, only rare dendritic cells in the oral epithelium were B7-2(+), but reactive cells were scattered about the interstitial spaces of the muscle. In all lymphoid tissues, Gl-1 strongly stained certain distinct regions that are occupied by dendritic cells and by macrophages. For dendritic cells, these include the thymic medulla, splenic periarterial sheaths, and lymph node deep cortex; for macrophages, the B7-2-rich regions included the splenic marginal zone and lymph node subcapsular cortex. Splenic B7-2(+) cells were accessible to labeling with GL-1 mAb given intravenously. Dendritic cell stimulation of T cells (DNA synthesis) during the mixed leukocyte reaction was significantly (35-65%) blocked by GL-1. The block could be enhanced by adding 1G10 anti-B7-1 or by using CTLA-4 Ig, a ligand for both B7-1 and B7-2. We conclude that B7-2, like other accessory molecules, is expressed by many types of antigen-presenting cells. However, the regulation and extent of B7-2 expression seems to differ among cell types. Dendritic cells express very high levels, in several sites in vivo and after maturation into strong accessory cells in culture. C1 KYOTO UNIV,FAC SCI,DEPT ZOOL,SAKYO KU,KYOTO 606,JAPAN. ROCKEFELLER UNIV,CELLULAR PHYSIOL & IMMUNOL LAB,NEW YORK,NY 10021. KANSAI MED UNIV,DEPT PATHOL 1,MORIGUCHI,OSAKA 570,JAPAN. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NIA,BETHESDA,MD 20892. JUNTENDO UNIV,SCH MED,DEPT IMMUNOL,BUNKYO KU,TOKYO 113,JAPAN. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,DIV ONCOGEN,SEATTLE,WA 98121. RI Steinman, Ralph/F-7729-2012 FU NIAID NIH HHS [AI-13013] NR 56 TC 518 Z9 524 U1 1 U2 18 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 NOV 1 PY 1994 VL 180 IS 5 BP 1849 EP 1860 DI 10.1084/jem.180.5.1849 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PP543 UT WOS:A1994PP54300027 PM 7525841 ER PT J AU BROWNING, PJ ROBERTS, DD ZABRENETZKY, V BRYANT, J KAPLAN, M WASHINGTON, RH PANET, A GALLO, RC VOGEL, T AF BROWNING, PJ ROBERTS, DD ZABRENETZKY, V BRYANT, J KAPLAN, M WASHINGTON, RH PANET, A GALLO, RC VOGEL, T TI APOLIPOPROTEIN-E (APOE), A NOVEL HEPARIN-BINDING PROTEIN INHIBITS THE DEVELOPMENT OF KAPOSIS SARCOMA-LIKE LESIONS IN BALB/C NU/NU MICE SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; LONG-TERM CULTURE; ONCOSTATIN-M; ENDOTHELIAL-CELLS; GROWTH-FACTOR; VIRUS INFECTION; ANGIOGENESIS; ATHEROSCLEROSIS; POLYSACCHARIDE; THROMBOSPONDIN AB Recombinant apolipoprotein E-3 (ApoE-3), expressed in Escherichia coli, was purified and used in an in vitro and an in vivo model system for acquired immunodeficiency syndrome-associated Kaposi's sarcoma (AIDS-KS). This protein blocked cell proliferation and chemotaxis of AIDS-KS cells in response to activated lymphocyte conditioned medium (AL-CM) and oncostatin M (OSM). ApoE-3 also inhibited the formation of neoangiogenic lesions induced in BALB/c nu/nu mice by AIDS-KS cells. These findings represent a novel and potentially less toxic therapeutic approach for the treatment of AIDS-KS. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NIDR,INTRAMURAL RES PROGRAM,BETHESDA,MD 20892. N SHORE UNIV HOSP,DEPT INTERNAL MED,DIV INFECT DIS & IMMUNOL,MANHASSET,NY 11030. BIOTECHNOL GEN LTD,DEPT BIOL MOLEC,IL-76326 REHOVOT,ISRAEL. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 43 TC 29 Z9 29 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 1 PY 1994 VL 180 IS 5 BP 1949 EP 1954 DI 10.1084/jem.180.5.1949 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PP543 UT WOS:A1994PP54300037 PM 7525844 ER PT J AU RACKE, MK BONOMO, A SCOTT, DE CANNELLA, B LEVINE, A RAINE, CS SHEVACH, EM ROCKEN, M AF RACKE, MK BONOMO, A SCOTT, DE CANNELLA, B LEVINE, A RAINE, CS SHEVACH, EM ROCKEN, M TI CYTOKINE-INDUCED IMMUNE DEVIATION AS A THERAPY FOR INFLAMMATORY AUTOIMMUNE-DISEASE SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; TUMOR-NECROSIS-FACTOR; MYELIN BASIC-PROTEIN; GROWTH-FACTOR-BETA; T-CELL CLONES; LEISHMANIA-MAJOR; GENE-EXPRESSION; IFN-GAMMA; IL-4; MICE AB The properties and outcome of an immune response are best predicted by the lymphokine phenotype of the responding T cells. Cytokines produced by CD4(+) T helper type 1 (Th1) T cells mediate delayed type hypersensitivity (DTH) and inflammatory responses, whereas cytokines produced by Th2 T cells mediate helper T cell functions for antibody production. To determine whether induction of Th2-like cells would modulate an inflammatory response, interleukin 4 (IL-4) was administered to animals with experimental allergic encephalomyelitis (EAE), a prototypic autoimmune disease produced by Th1-like T cells specific for myelin basic protein (MBP). IL-4 treatment resulted in amelioration of clinical disease, the induction of MBP-specific Th2 cells, diminished demyelination, and inhibition of the synthesis of inflammatory cytokines in the central nervous system (CNS). Modulation of an immune response from one dominated by excessive activity of Th1-like T cells to one dominated by the protective cytokines produced by Th2-like T cells may have applicability to the therapy of certain human autoimmune diseases. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. US FDA,CTR BIOL,BETHESDA,MD 20892. ALBERT EINSTEIN COLL MED,DIV NEUROPATHOL,BRONX,NY 10461. SEARLE MONSANTO CO,DEPT IMMUNOL,ST LOUIS,MO 63198. NR 36 TC 506 Z9 515 U1 0 U2 4 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 NOV 1 PY 1994 VL 180 IS 5 BP 1961 EP 1966 DI 10.1084/jem.180.5.1961 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PP543 UT WOS:A1994PP54300039 PM 7525845 ER PT J AU GUEGUEN, M BIDDISON, WE LONG, EO AF GUEGUEN, M BIDDISON, WE LONG, EO TI T-CELL RECOGNITION OF AN HLA-A2-RESTRICTED EPITOPE DERIVED FROM A CLEAVED SIGNAL SEQUENCE SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID CLASS-I; ANTIGEN PRESENTATION; LYMPHOCYTES-T; ENDOPLASMIC-RETICULUM; PRESENTATION PATHWAY; ENDOGENOUS PEPTIDES; MUTANT-CELLS; EXPRESSION; IDENTIFICATION; TRANSLOCATION AB An alternative pathway for class I-restricted antigen presentation has been suggested on the basis of peptides bound to HLA-A2 molecules in cells lacking the transporter for antigen presentation (TAP). Most of these peptides were derived from signal sequences for translocation into the endoplasmic reticulum (ER). However, it is not known whether these peptides can be presented to T cells. The hydrophobic nature of an HLA-A2-restricted T cell epitope (M1 58-66) was exploited to test whether it could be presented to T cells when derived from a signal sequence. Replacing the signal sequence of the influenza virus hemagglutinin molecule H3 with an artificial sequence containing that HLA-A2-restricted T cell epitope resulted in efficient translocation of H3 molecules into the ER and transport to the cell surface. This signal sequence-derived epitope was presented to HLA-A2-restricted T cells. Involvement of cytosolic processing for this presentation is very unlikely, because (a) presentation occurred in cells lacking TAP; (b) expression of H3 molecules with the artificial signal sequence did not produce a detectable cytosolic form of H3; and (c) presentation of the same epitope expressed in cytosolic forms of antigen required TAP. Thus, a peptide derived from a signal sequence cleaved in the ER can provide an epitope for HLA-A2-restricted T cell recognition. C1 NIAID,IMMUNOGENET LAB,ROCKVILLE,MD 20852. NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 31 TC 30 Z9 32 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 NOV 1 PY 1994 VL 180 IS 5 BP 1989 EP 1994 DI 10.1084/jem.180.5.1989 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PP543 UT WOS:A1994PP54300044 PM 7525846 ER PT J AU COHEN, JI SEIDEL, KE AF COHEN, JI SEIDEL, KE TI ABSENCE OF VARICELLA-ZOSTER VIRUS (VZV) GLYCOPROTEIN-V DOES NOT ALTER GROWTH OF VZV IN-VITRO OR SENSITIVITY TO HEPARIN SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID HERPES-SIMPLEX VIRUS; COMPLETE DNA-SEQUENCE; PSEUDORABIES VIRUS; GENE 14; TYPE-1; ADSORPTION; CELLS; GIII; NEUTRALIZATION; COMPONENT AB Varicella-zoster virus (VZV) encodes at least five glycoproteins, gpI to gpV. VZV gpV, M(r) 100K to 110K, is the product of VZV open reading frame (ORF) 14. VZV gpV is homologous to herpes simplex virus gC and pseudorabies virus gIII. To determine whether gpV is required for viral replication, we inserted a stop codon after the fifteenth codon of the ORF14 gene in a cosmid containing the gene. Transfection of human melanoma cells with the cosmid containing the mutant ORF14 gene and three other cosmids resulted in the production of infectious VZV. Immunoprecipitation indicated that the mutant virus did not express gpV. VZV that did not express gpV grew at the same rate as parental virus and was inhibited by heparin to a similar extent. The pattern of inhibition by heparin of the gpV mutant was similar to that reported for a herpes simplex virus mutant that does not contain gC, but different from that described for a pseudorabies virus mutant devoid of gIII. These results indicate that VZV gpV is not required for viral replication in vitro. RP COHEN, JI (reprint author), NIAID, CLIN INVEST LAB, BLDG 10, BETHESDA, MD 20892 USA. NR 27 TC 28 Z9 29 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD NOV PY 1994 VL 75 BP 3087 EP 3093 DI 10.1099/0022-1317-75-11-3087 PN 11 PG 7 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA PQ028 UT WOS:A1994PQ02800023 PM 7964618 ER PT J AU SEUANEZ, HN ALVES, G OBRIEN, SJ AF SEUANEZ, HN ALVES, G OBRIEN, SJ TI GENE-MAPPING IN THE SPIDER MONKEY (ATELES PANISCUS CHAMEK) SO JOURNAL OF HEREDITY LA English DT Article ID CEBUS-CAPUCINUS; DOMESTIC CAT; PAPIO-PAPIO; ASSIGNMENTS; PRIMATES; COMMITTEE; BABOON; RABBIT; GIBBON; MOUSE AB Sixteen isozyme markers have been assigned to the chromosome complement of the neotropical primate species Ateles paniscus chamek using three somatic cell hybrid panels. Several genetic associations were found to be common between humans and this species, despite the fact that Ateles is a karyologically rearranged taxon. Conversely, several human gene clusters were disrupted, resulting in gene associations not previously found in other primates. A comparison with other primates and mammalian orders, for which gene maps are available, was carried out for a comprehensive evaluation of genome evolution in these disparate taxa. C1 FED UNIV RIO DE JANEIRO,DEPT GENET,BR-21945 RIO JANEIRO,BRAZIL. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. RP SEUANEZ, HN (reprint author), INST NACL CANC,CTR PESQUISA BASICA,GENET SECT,PRACA CRUZ VERMELHA 23,6 ANDAR,BR-20230100 RIO JANEIRO,BRAZIL. NR 40 TC 10 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0022-1503 J9 J HERED JI J. Hered. PD NOV-DEC PY 1994 VL 85 IS 6 BP 466 EP 473 PG 8 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA PW576 UT WOS:A1994PW57600008 PM 7995927 ER PT J AU WESTERGAARD, GC SUOMI, SJ AF WESTERGAARD, GC SUOMI, SJ TI A SIMPLE STONE-TOOL TECHNOLOGY IN MONKEYS SO JOURNAL OF HUMAN EVOLUTION LA English DT Article DE CAPUCHIN; CEBUS-APELLA; HOMINID; LITHIC TECHNOLOGY; MONKEYS; TOOL-USE; TOOL, MANUFACTURE ID CEBUS-APELLA; SENSORIMOTOR INTELLIGENCE; OBJECT MANIPULATION; OLDUVAI GORGE; MANUFACTURE; HAMMERS; APES AB The purpose of this research was to examine the use and modification of stone tools by tufted capuchin monkeys (Cebus apella). Two experiments were conducted. In Experiment 1, six of 11 monkeys produced stone-flakes, by striking stones against hard surfaces. In Experiment 2, three of 15 monkeys used stones as cutting tools. Two of these monkeys combined tools and one of them modified stones prior to using them as tools. The results of this study demonstrate a simple stone-tool technology in monkeys. These data provide further evidence for cross-species continuity in the tool-using and tool-making abilities of primates and indicate that stone-tool technology may have evolved in the hominid lineage earlier than has been confirmed by the existing archaeological record. RP WESTERGAARD, GC (reprint author), NICHHD,COMPARAT ETHOL LAB,POB 529,POOLESVILLE,MD 20837, USA. NR 19 TC 22 Z9 22 U1 1 U2 4 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0047-2484 J9 J HUM EVOL JI J. Hum. Evol. PD NOV PY 1994 VL 27 IS 5 BP 399 EP 404 DI 10.1006/jhev.1994.1055 PG 6 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA PQ957 UT WOS:A1994PQ95700001 ER PT J AU KUMAR, AG DAI, XY KOZAK, CA MIMS, MP GOTTO, AM BALLANTYNE, CM AF KUMAR, AG DAI, XY KOZAK, CA MIMS, MP GOTTO, AM BALLANTYNE, CM TI MURINE VCAM-1 - MOLECULAR-CLONING, MAPPING, AND ANALYSIS OF A TRUNCATED FORM SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL-ADHESION MOLECULE-1; ANCHORED MEMBRANE-PROTEINS; MESSENGER-RNA DEGRADATION; NF-KAPPA-B; ENDOTHELIAL-CELLS; MOUSE; EXPRESSION; GENE; LYMPHOCYTES; BINDING AB Vascular cell adhesion molecule-1 (VCAM-1) is a member of the Ig superfamily that shows increased expression in a number of pathologic conditions. The role of VCAM-1 in human disease remains undefined and murine models are being extensively studied to help define the importance of VCAM-1 in inflammatory disorders. We have cloned and characterized the murine Vcam1 gene including 3 kb of 5'-flanking sequences and mapped the gene to chromosome 3 near Amy1. cDNA clones isolated from a stimulated hepatic library were found to encode a truncated form of VCAM-1 (T-VCAM-1) which contains Ig domains 1 through 3 and has a unique alternative carboxyl terminus. This form arises by alternative splicing. High level expression of T-VCAM-1 in transfected L cells was sufficient to support adhesion of lymphocytes, and this adhesion was blocked by Abs to VCAM-1. Treatment of transfected COS cells with phospholipase C led to reduced levels of T-VCAM-1 on the cell surface consistent with glycosylphosphatidylinositol linkage. Northern blot analysis showed that mRNA for T-VCAM-1 is inducible in multiple tissues after stimulation with endotoxin. Both forms of VCAM-1 were expressed in cultured endothelial, fibroblast, and aortic smooth muscle cells, whereas neither form was observed in monocyte- and lymphocyte-derived lines. Differential regulation of both forms of VCAM-1 was observed in the three different cell types that are present in the vessel wall. Thus, expression of VCAM-1 is restricted and controlled at the level of transcription and by alternative splicing. C1 BAYLOR COLL MED,DEPT INTERNAL MED,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. NIAID,BETHESDA,MD 20892. RI Ballantyne, Christie/A-6599-2008 FU NHLBI NIH HHS [HL-02537, HL-42550] NR 50 TC 28 Z9 29 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1994 VL 153 IS 9 BP 4088 EP 4098 PG 11 WC Immunology SC Immunology GA PN071 UT WOS:A1994PN07100025 PM 7523515 ER PT J AU WILLIAMS, MS HENKART, PA AF WILLIAMS, MS HENKART, PA TI APOPTOTIC CELL-DEATH INDUCED BY INTRACELLULAR PROTEOLYSIS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOTOXIC LYMPHOCYTES-T; DNA FRAGMENTATION; PROTEASE INHIBITORS; SERINE PROTEASES; MAMMALIAN-CELLS; CYTO-TOXICITY; GENE CED-3; ACTIVATION; ENDONUCLEASE; MEMBRANE AB To mimic the injection of granzymes into target cells by cytotoxic lymphocytes or the activation of endogenous proteases in programmed cell death, the proteases chymotrypsin, proteinase K, or trypsin were loaded into the cytoplasm of several different cell types using the osmotic lysis of pinosomes technique. internalization of these proteases caused cell lysis within several hours, accompanied by extensive nuclear damage in most but not all combinations of target cells and proteases. This nuclear damage, quantitated by DNA release from nuclei, was associated with apoptotic features including DNA fragmentation into nucleosomal ladders, chromatin condensation, nuclear fragmentation, and membrane blebbing. Agents reported to block programmed cell death, including aurintricarboxylic acid, inhibitors of energy metabolism, and protein or RNA synthesis, failed to block this protease-induced death, although some inhibited nuclear damage. In separate experiments, introduction of staphylococcal nuclease into cells led to near complete (at least 75% of total) nucleosomal DNA fragmentation within 6 to 8 h. Condensation of chromatin did not accompany this fragmentation to the same extent, and there was approximately a 10-h lag between half-maximal DNA fragmentation and 50% loss of membrane integrity. The results suggest that activation of intracellular proteases during cell death by any molecular pathway could give rise to apoptotic morphology and DNA fragmentation. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NR 42 TC 121 Z9 122 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1994 VL 153 IS 9 BP 4247 EP 4255 PG 9 WC Immunology SC Immunology GA PN071 UT WOS:A1994PN07100041 PM 7930626 ER PT J AU MACIEJEWSKI, JP WEICHOLD, FF YOUNG, NS AF MACIEJEWSKI, JP WEICHOLD, FF YOUNG, NS TI HIV-1 SUPPRESSION OF HEMATOPOIESIS IN-VITRO MEDIATED BY ENVELOPE GLYCOPROTEIN AND TNF-ALPHA SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; HUMAN-BONE-MARROW; IMMUNE-DEFICIENCY-SYNDROME; AIDS-RELATED COMPLEX; T-CELL CLONES; PROGENITOR CELLS; MONONUCLEAR PHAGOCYTES; PERIPHERAL-BLOOD; HIV-1-INFECTED SUBJECTS AB Dysmorphic marrow morphology and bone marrow failure are common in AIDS patients, but the mechanism of HIV-1 effects on blood cell production is unclear. Experiments to test the susceptibility of hematopoietic progenitor cells to HIV-1 infection have led to conflicting results. We found that hematopoietic colony formation by burst-forming units-erythroid and CFU-GM was equivalently inhibited by both active and heat-inactivated, noninfectious virus. Inhibition was dependent on the presence of macrophages and was not observed in cultures derived from highly enriched CD34(+) cells. We hypothesized that TNF-alpha, produced by mononuclear phagocytes after contact with HIV-1 or gp120 and itself a potent suppressor of hematopoiesis, might mediate this effect. The addition of anti-TNF-alpha neutralizing Abs to marrow cultures abrogated inhibition by gp120 or virus. In contrast, neutralizing Abs to IL-4, IFN-alpha, and TGF-beta failed to improve colony formation. TNF-alpha was released from blood monocytes and marrow mononuclear cells stimulated by gp120. TNF-alpha is increased in the blood of patients with late stage AIDS and may mediate many of the symptoms of the disease. Our data do not support a requirement of direct infection of hematopoietic progenitor cells by HIV-1 for the inhibition of hematopoiesis in vitro. We propose instead an indirect mechanism of viral suppression of hematopoiesis as a result of TNF-alpha induction by virus or viral envelope glycoprotein. The importance of local TNF-alpha production in patients' marrow is amenable to clinical testing. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RP MACIEJEWSKI, JP (reprint author), NHLBI,HEMATOL BRANCH,BLDG 10,ROOM 7C112,BETHESDA,MD 20892, USA. NR 45 TC 58 Z9 58 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1994 VL 153 IS 9 BP 4303 EP 4310 PG 8 WC Immunology SC Immunology GA PN071 UT WOS:A1994PN07100046 PM 7523521 ER PT J AU TINUBU, SA HAKIMI, J KONDAS, JA BAILON, P FAMILLETTI, PC SPENCE, C CRITTENDEN, MD PARENTEAU, GL DIRBAS, FM TSUDO, M BACHER, JD KASTENSPORTES, C MARTINUCCI, JL GOLDMAN, CK CLARK, RE WALDMANN, TA AF TINUBU, SA HAKIMI, J KONDAS, JA BAILON, P FAMILLETTI, PC SPENCE, C CRITTENDEN, MD PARENTEAU, GL DIRBAS, FM TSUDO, M BACHER, JD KASTENSPORTES, C MARTINUCCI, JL GOLDMAN, CK CLARK, RE WALDMANN, TA TI HUMANIZED ANTIBODY-DIRECTED TO THE IL-2 RECEPTOR BETA-CHAIN PROLONGS PRIMATE CARDIAC ALLOGRAFT SURVIVAL SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERLEUKIN-2 RECEPTOR; MONOCLONAL-ANTIBODY; RENAL-TRANSPLANTATION; TAC ANTIBODY; SUBUNIT; COMPLEX; BINDING; CELLS; P75; IL-2-RECEPTOR AB IL-2Rs are expressed by T cells activated in response to foreign histocompatibility Ags but not by normal cells. This difference in IL-2R expression is exploited by blockade of IL-2Rs to achieve immunosuppression. High affinity IL-2Rs involve three subunits, IL-2R alpha, IL-2R beta, and IL-2R gamma. Murine Mik beta 1, a mAb that blocks IL-2 binding to IL-2R beta, was developed as an immunosuppressive agent. There was modest prolongation of cynomolgus cardiac allograft survival in animals treated with murine Mik beta 1 (mean survival 11.8 +/- 1.6 days compared with 8.2 +/- 0.4 days in untreated animals; p = 0.06). However, murine Mik beta 1 is ineffective in recruiting primate effector cells and is neutralized by monkey Abs directed toward the infused Ab. To circumvent these limitations, a humanized form of Mik beta 1, which is a largely human IgG1k Ab, except that murine hypervariable regions are retained, was developed. In vivo plasma survival of humanized Mik beta 1 was threefold longer than simultaneously administered murine Mik beta 1 (terminal 4(1/2), 104 +/- 10 h vs 37 +/- 2 h). Furthermore, humanized Mik beta 1 manifests Ab-dependent cellular cytotoxicity, an activity that is absent with the parental murine Mik beta 1. Graft survival was significantly prolonged by humanized Mik beta 1 treatment with survivals of 22, 22, 24, 27, 44, and >300 days (p vs control <0.01; p vs murine Mik beta 1 <0.01). Survival was not prolonged further (p > 0.3) by the addition of humanized anti-Tac, which blocks interaction of IL-2 with IL-2R alpha subunits. There was no toxicity attributable to the use of Mik beta 1 Abs. Thus, humanized Mik beta 1 prolonged cardiac allograft survival in primates without toxicity and may be effective as an adjunct to standard immunosuppressive therapy. C1 NCI,METAB BRANCH,BETHESDA,MD 20892. HOFFMANN LA ROCHE INC,ROCHE RES CTR BIOTECHNOL,NUTLEY,NJ 07110. HOWARD UNIV,MED CTR,WASHINGTON,DC 20059. NHLBI,SURG BRANCH,BETHESDA,MD 20892. KYOTO KATSUARA HOSP,KYOTO,JAPAN. NIH,NATL CTR RES RESOURCES,VET RES PROGRAM,BETHESDA,MD 20892. ALLEGHENY SINGER RES INST,PITTSBURGH,PA 15212. HOFFMANN LA ROCHE INC,ROCHE RES CTR,INFLAMMAT & AUTOIMMUNE DIS,NUTLEY,NJ 07110. NR 39 TC 37 Z9 40 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 NOV 1 PY 1994 VL 153 IS 9 BP 4330 EP 4338 PG 9 WC Immunology SC Immunology GA PN071 UT WOS:A1994PN07100049 PM 7930631 ER PT J AU YAMAUE, H KASHMIRI, SVS DEFILIPPI, R NIERODA, C YANNELLI, JR TSANG, KY SCHLOM, J AF YAMAUE, H KASHMIRI, SVS DEFILIPPI, R NIERODA, C YANNELLI, JR TSANG, KY SCHLOM, J TI ENHANCED INTERLEUKIN-2 PRODUCTION IN HUMAN TUMOR-INFILTRATING LYMPHOCYTES ENGINEERED BY 3'-TRUNCATED INTERLEUKIN-2 GENE SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE TUMOR-INFILTRATING LYMPHOCYTE; HUMAN INTERLEUKIN-2 GENE; RETROVIRAL VECTOR ID RETROVIRAL VECTORS; NECROSIS-FACTOR; CELL-LINES; IL-2 GENE; METASTATIC MELANOMA; HIGHLY EFFICIENT; T-CELLS; EXPRESSION; CDNA; TUMORIGENICITY AB Tumor-infiltrating lymphocytes (TILs), T lymphocytes associated with solid tumors that can be grown with interleukin (IL)-2 in vitro, preferentially accumulate at tumor sites after adoptive transfer. Therefore, TILs can be considered for use as cellular vehicles in gene therapy. We transduced melanoma TILs with the IL-2 gene and clarified functional characteristics of the TIL transductants. TILs transduced with 3'-end-truncated IL-2 gene (480 bp) produced high amounts of IL-2 detected in supernatants when compared to TILs transduced with the native IL-2 gene containing 3'-end adenine-thymidine (AT)-rich sequences (650 bp). The level of IL-2 in supernatants was higher with the addition of anti-Tac antibody (Ab) to block the consumption of IL-2 by the TILs. These TILs could proliferate autonomously in the absence of exogenous IL-2, and the proliferation of TILs could be completely blocked by anti-IL-2 Ab or anti-IL-2 receptor Ab. Thus TILs transduced with IL-2 gene can proliferate through the autocrine loop. However, the expression of IL-2 from TILs transduced with the IL-2 gene was downregulated after 2 to 3 weeks of G418 selection. Our study indicates the feasibility of transduction and expression of a truncated 480-bp IL-2 gene into TILs and the possibility of employing adoptive immunotherapy protocols using TILs modified with this IL-2 gene. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. NR 47 TC 9 Z9 10 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV PY 1994 VL 16 IS 4 BP 262 EP 274 DI 10.1097/00002371-199411000-00002 PG 13 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA PX986 UT WOS:A1994PX98600002 PM 7881635 ER PT J AU BEI, R KANTOR, J KASHMIRI, SVS ABRAMS, S SCHLOM, J AF BEI, R KANTOR, J KASHMIRI, SVS ABRAMS, S SCHLOM, J TI ENHANCED IMMUNE-RESPONSES AND ANTITUMOR-ACTIVITY BY BACULOVIRUS RECOMBINANT CARCINOEMBRYONIC ANTIGEN (CEA) IN MICE PRIMED WITH THE RECOMBINANT VACCINIA CEA SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE RECOMBINANT HUMAN CEA; BACULOVIRUS; VACCINIA VIRUS; IMMUNOGENICITY; BOOST ID VIRUS-VACCINE; GENE; SAFETY; IMMUNOGENICITY; GLYCOPROTEIN AB Carcinoembryonic antigen (CEA), a glycosylated protein of Mr 180, is one of the most widely studied oncofetal antigens. A majority of gastrointestinal cancers as well as breast and non-small-cell lung carcinomas express CEA. CEA thus represents a potential target for immunotherapy of several carcinoma types. A recombinant vaccinia-CEA virus (rV-CEA) was previously shown to induce anti-tumor activity in an experimental murine model after three rV-CEA inoculations. However, because the majority of cancer patients have received a previous smallpox vaccination, a long-lasting immune memory and/or induced anamnestic responses against vaccinia proteins may prevent repetitive boosting with the recombinant vaccinia virus expressing CEA. Therefore, other types of vaccines may be required to boost the anti-CEA immune response; one such schema would be the use of purified CEA as a boost in hosts given one administration of rV-CEA. Commercially available sources of CEA are usually derived from liver metastases extracts and are sometimes contaminated with nonspecific cross-reactive antigen. We have previously generated a recombinant source of full-length human CEA using a baculovirus expression system (bV-CEA). bV-CEA was shown to be glycosylated differently than native CEA, but it contains at least 10 epitopes found on native CEA (nCEA). Moreover, bV-CEA was able to induce a humoral response against CEA present on human colorectal cancer cell lines. We have investigated here the effectiveness of bV-CEA and nCEA to boost both humoral and T-cell responses after a primary vaccination with the recombinant CEA vaccinia vaccine. The results indicate that the combination immunization regimen based on priming with rV-CEA followed by a bV-CEA boost is superior in the induction of immune responses and anti-tumor activity than using bV-CEA alone or one inoculation of rV-CEA as vaccine. The studies reported here thus provide evidence for the use of bV-CEA as a boost following primary immunization with rV-CEA. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NR 23 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 NOV PY 1994 VL 16 IS 4 BP 275 EP 282 DI 10.1097/00002371-199411000-00003 PG 8 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA PX986 UT WOS:A1994PX98600003 PM 7881636 ER PT J AU LAM, KS GUSTAVSON, DR VEITCH, JM FORENZA, S ROSS, J MILLER, D ROACH, J LEBHERZ, WB POOLE, K AF LAM, KS GUSTAVSON, DR VEITCH, JM FORENZA, S ROSS, J MILLER, D ROACH, J LEBHERZ, WB POOLE, K TI LARGE-SCALE PRODUCTION AND SEMI-PURIFICATION OF KEDARCIDIN IN A 1000-L FERMENTER SO JOURNAL OF INDUSTRIAL MICROBIOLOGY LA English DT Article DE KEDARCIDIN; ANTITUMOR ANTIBIOTIC; CHROMOPROTEIN ID PHYSICOCHEMICAL PROPERTIES; BIOLOGICAL-ACTIVITY; SP-NOV; ANTITUMOR; SACCHAROTHRIX; CHROMOPHORE; TAXONOMY; ORGANISM; PROTEIN; C-1027 AB Actinomycete strain ATCC 53650 was grown in a 1000-L fermentor containing 680 L of medium and the production of kedarcidin was monitored by HPLC. The titers of kedarcidin in the fermentor cultures were 0.49-0.53 mg ml-1. A quick and efficient purification method involving the use of anion exchange resin DE23 (batch adsorption-desorption) and ultrafiltration system yielded high recovery (65% yield) of kedarcidin from the fermentor culture. Over 200 grams of lyophilized kedarcidin of 70% purity was recovered from each of two 1000-L fermentor cultures using this process. C1 FREDERICK CANC RES & DEV CTR,FREDERICK,MD. RP LAM, KS (reprint author), BRISTOL MYERS SQUIBB CO,PHARMACEUT RES INST,DEPT 114,POB 5100,WALLINGFORD,CT 06492, USA. NR 17 TC 4 Z9 4 U1 1 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0169-4146 J9 J IND MICROBIOL JI J. Indust. Microbiol. PD NOV PY 1994 VL 13 IS 6 BP 356 EP 360 DI 10.1007/BF01577219 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA PY266 UT WOS:A1994PY26600004 PM 7765667 ER PT J AU MANOS, MM WALDMAN, J ZHANG, TY GREER, CE EICHINGER, G SCHIFFMAN, MH WHEELER, CM AF MANOS, MM WALDMAN, J ZHANG, TY GREER, CE EICHINGER, G SCHIFFMAN, MH WHEELER, CM TI EPIDEMIOLOGY AND PARTIAL NUCLEOTIDE-SEQUENCE OF 4 NOVEL GENITAL HUMAN PAPILLOMAVIRUSES SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID INFECTION; DETERMINANTS; WOMEN; PCR AB Polymerase chain reaction (PCR)-based genital human papillomavirus (HPV) detection methods that use consensus primers have enabled the broad-spectrum detection of most characterized HPV types. In addition, these techniques have allowed the identification of potentially novel viral sequences in clinical specimens. These methods were used to determine the partial L1 nucleotide sequence (the region generated by L1 consensus primers MY09 and MY11) of four novel viruses. The prevalence of these viruses in cytologically normal and dysplastic cervical specimens and in invasive cervical cancer was also determined. The partial DNA sequences of W13B (MM4), PAP291 (MM7), PAP155 (MM8), and PAP238a (MM9) are most similar to HPV-51, -61, -61, and -34, respectively. Prevalence studies suggest that W13B and PAP238a are cancer-associated, while PAP155 and PAP291 appear to be lower-risk viruses. C1 CETUS CORP,DEPT INFECT DIS,EMERYVILLE,CA 94608. PLANNED PARENTHOOD,LAFAYETTE,CA. SHASTA DIABLO PLANNED PARENTHOOD,CONCORD,CA. NCI,BETHESDA,MD. UNIV NEW MEXICO,TUMOR REGISTRY,ALBUQUERQUE,NM. RP MANOS, MM (reprint author), JOHNS HOPKINS UNIV,SCH PUBL HLTH,DEPT MOLEC MICROBIOL & IMMUNOL,615 N WOLFE ST,BALTIMORE,MD 21205, USA. FU NIAID NIH HHS [AI-32917]; PHS HHS [MA-5623-20, MA-5623-41] NR 16 TC 58 Z9 64 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 NOV PY 1994 VL 170 IS 5 BP 1096 EP 1099 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PN668 UT WOS:A1994PN66800008 PM 7963700 ER PT J AU DEWAR, RL HIGHBARGER, HC SARMIENTO, MD TODD, JA VASUDEVACHARI, MB DAVEY, RT KOVACS, JA SALZMAN, NP LANE, HC URDEA, MS AF DEWAR, RL HIGHBARGER, HC SARMIENTO, MD TODD, JA VASUDEVACHARI, MB DAVEY, RT KOVACS, JA SALZMAN, NP LANE, HC URDEA, MS TI APPLICATION OF BRANCHED DNA SIGNAL AMPLIFICATION TO MONITOR HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 BURDEN IN HUMAN PLASMA SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID POLYMERASE CHAIN-REACTION; HIV P24 ANTIGEN; PERIPHERAL-BLOOD; INFECTED INDIVIDUALS; HEPATITIS-C; AIDS; VIREMIA; QUANTITATION; CELLS; RNA AB A branched DNA (bDNA)-based quantitation of plasma human immunodeficiency virus type 1 (HIV-1) RNA was used to monitor the virologic status of 102 patients (29-906 CD4 cells/ mm(3)) enrolled in clinical trials of antiretroviral and immune-based therapies. Virion-associated RNA was measurable in plasma of 74% of patients tested (10,000-10,000,000 RNA equivalents/mL). Virus levels measured by the bDNA assay exceeded titers obtained by quantitative plasma culture and were inversely correlated (r = -.378; P < .05) with total CD4 cell counts. The assay was used to demonstrate a significant decline (mean, 5-fold; range, 0- to 30-fold), relative to pretreatment, in virus load after beginning antiviral therapy and a transient increase (mean, 15-fold; range, 2- to 50-fold) after treatment with interleukin-2. The decrease in RNA was more dramatic than changes in serum p24 antigen. The bDNA assay yields reproducible results, is relatively easy, and should be useful in measuring HIV-1 RNA in patients in clinical trials. C1 GEORGETOWN UNIV,MED CTR,DEPT MICROBIOL,MOLEC RETROVIROL LAB,WASHINGTON,DC 20007. CHIRON CORP,EMERYVILLE,CA. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-05058] NR 43 TC 163 Z9 164 U1 0 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV PY 1994 VL 170 IS 5 BP 1172 EP 1179 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PN668 UT WOS:A1994PN66800018 PM 7963710 ER PT J AU DAVEY, RT BOENNING, CM HERPIN, BR BATTS, DH METCALF, JA WATHEN, L COX, SR POLIS, MA KOVACS, JA FALLOON, J WALKER, RE SALZMAN, N MASUR, H LANE, HC AF DAVEY, RT BOENNING, CM HERPIN, BR BATTS, DH METCALF, JA WATHEN, L COX, SR POLIS, MA KOVACS, JA FALLOON, J WALKER, RE SALZMAN, N MASUR, H LANE, HC TI USE OF RECOMBINANT SOLUBLE CD4 PSEUDOMONAS EXOTOXIN, A NOVEL IMMUNOTOXIN, FOR TREATMENT OF PERSONS INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ANTI-HIV ACTIVITY; CD4-PSEUDOMONAS EXOTOXIN; HYBRID PROTEIN; ENVELOPE GLYCOPROTEINS; CELLS; CYTOTOXICITY; LYMPHOCYTES; INVITRO AB Single and multiple doses of sCD4-PE40, a soluble recombinant fusion toxin selectively toxic to gp120-expressing cells, were evaluated in persons infected with human immunodeficiency virus type 1 (HIV-1). Seventeen of 24 patients who completed a single-dose safety trial were given either 1, 5, 10, or 15 mu g/kg of sCD4-PE40 by intravenous bolus once a month for 2 months, then weekly for 6 weeks. The weekly maximally tolerated dose was 10 mu g/kg. The major toxicity was a transient dose-dependent elevation in hepatic aminotransferases peaking 48 h after infusion. Anti-Pseudomonas exotoxin antibody developed in 58% of recipients, and sera from 13 of 17 showed neutralizing activity against sCD4-PE40. No consistent changes in immunologic or virologic markers were observed. Weekly infusions of less than or equal to 10 mu g/kg of sCD4-PE40 are generally well tolerated, but additional studies correlating optimal dosing and frequency of administration with efficacy will be needed to define the role of this novel agent in the management of HIV-1-infected patients. C1 NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892. UPJOHN CO,KALAMAZOO,MI. GEORGETOWN UNIV,MED CTR,DIV MOLEC VIROL & IMMUNOL,WASHINGTON,DC 20007. RP DAVEY, RT (reprint author), NIAID,BLDG 10,ROOM 11C103,BETHESDA,MD 20892, USA. OI Polis, Michael/0000-0002-9151-2268 NR 18 TC 43 Z9 46 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV PY 1994 VL 170 IS 5 BP 1180 EP 1188 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PN668 UT WOS:A1994PN66800019 PM 7963711 ER PT J AU BACELLAR, H MUNOZ, A HOOVER, DR PHAIR, JP BESLEY, DR KINGSLEY, LA VERMUND, SH AF BACELLAR, H MUNOZ, A HOOVER, DR PHAIR, JP BESLEY, DR KINGSLEY, LA VERMUND, SH TI INCIDENCE OF CLINICAL AIDS CONDITIONS IN A COHORT OF HOMOSEXUAL MEN WITH CD4(+) CELL COUNTS LESS-THAN-100/MM(3) SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID IMMUNODEFICIENCY-SYNDROME AIDS; VIRUS HIV INFECTION; LYMPHOCYTE COUNTS; PROPHYLAXIS; THERAPY AB Incidence rates of AIDS illnesses are described among patients with less than or equal to 100 CD4 cells/mm(3) grouped by use of antiretrovirals and chemoprophylaxis. Data were obtained from 2646 homosexual men infected with human immunodeficiency virus type 1. Participants were in the Multicenter AIDS Cohort Study during 1985-1993. The incidence rates per 100 person-years for Pneumocystis carinii pneumonia were 47.4 without treatment, 21.5 with antiretrovirals alone, and 12.8 with antiretrovirals combined with chemoprophylaxis. For Kaposi's sarcoma these rates were 23.2, 11.3, and 15.1, respectively. The incidence of some opportunistic infections, including Mycobacterium avium complex, nonretinitis cytomegalovirus disease, and cytomegalovirus retinitis, increased among persons receiving P. carinii pneumonia prophylaxis, because of reduction of this pneumonia and extension of life span. The incidence pattern of AIDS-defining illnesses in patients receiving treatment points to the changing AIDS epidemic and the need for new therapies. The data are particularly relevant to the development and planning of clinical trials and to health care providers. C1 JOHNS HOPKINS UNIV,SCH PUBL HLTH,BALTIMORE,MD 21205. NIAID,BETHESDA,MD 20892. NORTHWESTERN UNIV,SCH MED,EVANSTON,IL. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,LOS ANGELES,CA. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,PITTSBURGH,PA. FU NIAID NIH HHS [AI-35043, AI-35039, AI-35042] NR 12 TC 36 Z9 36 U1 1 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV PY 1994 VL 170 IS 5 BP 1284 EP 1287 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PN668 UT WOS:A1994PN66800036 PM 7963728 ER PT J AU CHERNESKY, MA LEE, H SCHACHTER, J BURCZAK, JD STAMM, WE MCCORMACK, WM QUINN, TC AF CHERNESKY, MA LEE, H SCHACHTER, J BURCZAK, JD STAMM, WE MCCORMACK, WM QUINN, TC TI DIAGNOSIS OF CHLAMYDIA-TRACHOMATIS URETHRAL INFECTION IN SYMPTOMATIC AND ASYMPTOMATIC MEN BY TESTING FIRST-VOID URINE IN A LIGASE CHAIN-REACTION ASSAY SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID 1ST-VOID URINE; IMMUNOASSAY; SAMPLES; SPECIMENS; ANTIGENS; CULTURES; SWABS AB A multicenter study compared ligase chain reaction (LCR) of Chlamydia trachomatis plasmid DNA with culture of urethral swab specimens from 542 men (study A); a second study (B) compared LCR offirst-void urine (FVU) with urethral swab cultures from 1043 men. Discordant results were resolved with direct fluorescent antibody staining of sediments from the FVU or urethral culture specimen and with a second LCR directed against a fragment of the major outer membrane protein gene. Test performance was calculated on the basis of an expanded reference standard. The LCR plasmid assay had a sensitivity of 98.0% in study A and 93.5% in study B; specificity was 99.8%-100%. The sensitivity of culturing urethral swabs from all study sites was 68.2% (range by sites, 40.0%-84.6%). The presence or absence of urethral symptoms did not alter the results. Use of this LCR test should allow more meaningful investigation and treatment of C. trachomatis infections in men. C1 ABBOTT LABS,PROBE DIAGNOST BUSINESS UNIT,ABBOTT PK,IL 60064. UNIV CALIF SAN FRANCISCO,SCH MED,SAN FRANCISCO,CA. UNIV WASHINGTON,HARBORVIEW MED CTR,SEATTLE,WA 98104. UNIV WASHINGTON,SCH MED,SEATTLE,WA. SUNY HLTH SCI CTR,BROOKLYN,NY 11203. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. NIAID,BETHESDA,MD 20892. RP CHERNESKY, MA (reprint author), MCMASTER UNIV,ST JOSEPHS HOSP,REG VIROL & CHLAMYDIOL LAB,50 CHARLTON AVE E,HAMILTON L8N 4A6,ON,CANADA. RI Quinn, Thomas/A-2494-2010 NR 15 TC 125 Z9 128 U1 1 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV PY 1994 VL 170 IS 5 BP 1308 EP 1311 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PN668 UT WOS:A1994PN66800042 PM 7963734 ER PT J AU MAHANTY, S DAY, KP ALPERS, MP KAZURA, JW AF MAHANTY, S DAY, KP ALPERS, MP KAZURA, JW TI ANTIFILARIAL IGG4 ANTIBODIES IN CHILDREN FROM FILARIA-ENDEMIC AREAS CORRELATE WITH DURATION OF INFECTION AND ARE DISSOCIATED FROM ANTIFILARIAL IGE ANTIBODIES SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID HAITIAN PEDIATRIC POPULATION; PAPUA-NEW-GUINEA; BANCROFTIAN FILARIASIS; IMMUNE RESPONSIVENESS; SUBCLASS ANTIBODIES; RESPONSES; ANTIGEN; QUANTITATION AB To investigate the relationship of antifilarial IgG4 and IgE to the intensity of transmission and duration of filarial infections in endemic populations, antifilarial antibody levels in children residing in a village in Papua New Guinea where transmission of Wuchereria ia bancrofti was reduced by repeated insecticide spraying were compared with levels in residents of three nearby villages where no control measures had been used. Antifilarial IgG4 levels were significantly lower in children from the sprayed village than in children or adults in nonsprayed villages (P < .01) and correlated with age (P < .05) and intensity of microfilaremia (P < .01). In contrast, antifilarial IgE was elevated to similar levels in children and adults from both villages. Antifilarial IgG4 (and not IgE) levels in endemic populations appear to be directly related to the duration of infection or to the cumulative exposure to infective vectors. C1 UNIV OXFORD,DEPT ZOOL,OXFORD,ENGLAND. PAPUA NEW GUINEA INST MED RES,GOROKA,PAPUA N GUINEA. CASE WESTERN RESERVE UNIV,DEPT MED,DIV GEOG MED,CLEVELAND,OH. RP MAHANTY, S (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. RI Day, Karen/F-3697-2015; OI Day, Karen/0000-0002-6115-6135; Mahanty, Siddhartha/0000-0003-1068-0524 FU NIAID NIH HHS [AI-15351] NR 15 TC 24 Z9 24 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV PY 1994 VL 170 IS 5 BP 1339 EP 1343 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PN668 UT WOS:A1994PN66800050 PM 7963742 ER PT J AU ADA, G ALBRECHT, P BEALE, J BELLINI, WJ BLOOM, B CHOPPIN, PW CHU, CM CLEMENTS, CJ CUTTS, F DEQUADROS, C GELLIN, BG GRIFFIN, DE HALSTEAD, SB HENDERSON, DA HILL, T JOHN, TJ KATZ, SL KUNOSAKAI, H LAMBERT, PH LUCAS, A MARKOWITZ, LE MARTINEZ, LJ MEEGAN, J MIMS, C MINOR, P NATHANSON, N NORRBY, E OLDSTONE, MBA OSTERHAUS, ADME PERVIKOV, Y RUSSELL, PK SCOTT, RM SHEPARD, D TERMEULEN, V AF ADA, G ALBRECHT, P BEALE, J BELLINI, WJ BLOOM, B CHOPPIN, PW CHU, CM CLEMENTS, CJ CUTTS, F DEQUADROS, C GELLIN, BG GRIFFIN, DE HALSTEAD, SB HENDERSON, DA HILL, T JOHN, TJ KATZ, SL KUNOSAKAI, H LAMBERT, PH LUCAS, A MARKOWITZ, LE MARTINEZ, LJ MEEGAN, J MIMS, C MINOR, P NATHANSON, N NORRBY, E OLDSTONE, MBA OSTERHAUS, ADME PERVIKOV, Y RUSSELL, PK SCOTT, RM SHEPARD, D TERMEULEN, V TI A BELLAGIO CONSENSUS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article C1 AUSTRALIAN NATL UNIV, JOHN CURTIN SCH MED RES, DIV CELL BIOL, CANBERRA, ACT 2601, AUSTRALIA. US FDA, CTR BIOL EVALUAT & RES, DIV VIROL, BETHESDA, MD USA. PRIESTS HOUSE, CRANBROOK, KENT, ENGLAND. CTR DIS CONTROL & PREVENT, NATL CTR INFECT DIS, MEASLES VIRUS SECT, ATLANTA, GA USA. ALBERT EINSTEIN COLL MED, DEPT MICROBIOL & IMMUNOL, BRONX, NY 10467 USA. HOWARD HUGHES MED INST, BETHESDA, MD 20817 USA. INST VIROL, BEIJING, PEOPLES R CHINA. WHO, EXPANDED PROGRAMME IMMUNIZAT, CH-1211 GENEVA, SWITZERLAND. LONDON SCH HYG & TROP MED, COMMUNICABLE DIS EPIDEMIOL UNIT, LONDON WC1, ENGLAND. PAN AMER HLTH ORG, EXPANDED PROGRAMME IMMUNIZAT, WASHINGTON, DC USA. JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, DEPT INT HLTH, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT MED, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROBIOL, BALTIMORE, MD USA. ROCKEFELLER FDN, DIV HLTH SCI, NEW YORK, NY USA. US PHS, WASHINGTON, DC USA. UNICEF, CHILD SURVIVAL UNIT, NEW YORK, NY USA. CHRISTIAN MED COLL & HOSP, DEPT VIROL & IMMUNOL, VELLORE 632004, TAMIL NADU, INDIA. DUKE UNIV, MED CTR, DEPT PEDIAT PEDIAT HLTH POLICY & INFECT DIS, DURHAM, NC USA. TOKAI UNIV, SCH MED, DEPT PEDIAT, ISEHARA, KANAGAWA, JAPAN. WHO, DIV MICROBIOL & IMMUNOL COMMUNICABLE DIS, CH-1211 GENEVA, SWITZERLAND. HARVARD UNIV, SCH MED, DEPT POPULAT & INT HLTH, BOSTON, MA USA. CTR DIS CONTROL & PREVENT, CTR PREVENT SERV, DIV IMMUNIZAT, ATLANTA, GA USA. WHO, CHILDRENS VACCINE INITIAT EXECUT SECRETARIAT, GENEVA, SWITZERLAND. NIAID, DIV MICROBIOL & INFECT DIS, BETHESDA, MD 20892 USA. SHERIFF HOUSE, ARDINGLY, W SUSSEX, ENGLAND. NATL INST BIOL STAND & CONTROLS, DIV VIROL, POTTERS BAR, HERTS, ENGLAND. UNIV PENN, SCH MED, DEPT MICROBIOL, PHILADELPHIA, PA 19104 USA. KAROLINSKA INST, DEPT VIROL, STOCKHOLM, SWEDEN. Scripps Res Inst, DEPT NEUROPHARMACOL RES, LA JOLLA, CA USA. NATL INST PUBL HLTH & ENVIRONM PROTECT, IMMUNOBIOL LAB, 3720 BA BILTHOVEN, NETHERLANDS. WHO, EXPANDED PROGRAMME IMMUNIZAT, CH-1211 GENEVA, SWITZERLAND. BRANDEIS UNIV, INST HLTH POLICY, WALTHAM, MA 02254 USA. UNIV WURZBURG, INST VIROL & IMMUNOBIOL, W-8700 WURZBURG, GERMANY. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV PY 1994 VL 170 SU 1 BP S63 EP S66 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PP335 UT WOS:A1994PP33500008 ER PT J AU SHI, XL ROJANASAKUL, Y GANNETT, P LIU, KJ MAO, Y DANIEL, LN AHMED, N SAFFIOTTI, U AF SHI, XL ROJANASAKUL, Y GANNETT, P LIU, KJ MAO, Y DANIEL, LN AHMED, N SAFFIOTTI, U TI GENERATION OF THIYL AND ASCORBYL RADICALS IN THE REACTION OF PEROXYNITRITE WITH THIOLS AND ASCORBATE AT PHYSIOLOGICAL PH SO JOURNAL OF INORGANIC BIOCHEMISTRY LA English DT Article ID ELECTRON-SPIN-RESONANCE; NITRIC-OXIDE; HYDROPEROXIDE-HEMATIN; LIPID-PEROXIDATION; SUPEROXIDE; OXIDATION; GLUTATHIONE; INTERMEDIATE; REDUCTION; ATTACK AB Electron spin resonance (ESR) spin trapping was utilized to investigate the reaction of peroxynitrite with thiols and ascorbate at physiological pH. The spin trap used was 5,5-dimethyl-1-pyrroline N-oxide (DMPO). The reaction of peroxynitrite with DMPO generated 5,5-dimethylpyrrolidone-(2)-oxy-(1) (DMPOX). Formate enhanced the peroxynitrite decomposition but did not generate any detectable amount of formate-derived free radicals. Thus, the spin trapping measurements provided no evidence for hydroxyl ((OH)-O-.) radical generation in peroxynitrite decomposition at physiological pH. Thiols (glutathione, cysteine, and penicillamine) and ascorbate reacted with peroxynitrite to generate the corresponding thiyl and ascorbyl radicals. The one-electron oxidation of thiols by peroxynitrite may be one of the important mechanisms for peroxynitrite-induced toxicity and ascorbate may provide a detoxification pathway. C1 W VIRGINIA UNIV,DEPT PHARMACEUT SCI,MORGANTOWN,WV. DARTMOUTH COLL,DEPT RADIOL,HANOVER,NH. RP SHI, XL (reprint author), NCI,EXPTL PATHOL LAB,BLDG 41,ROOM C301,BETHESDA,MD 20892, USA. RI Shi, Xianglin/B-8588-2012; Gannett, Peter/J-3347-2015; OI Gannett, Peter/0000-0002-7859-5468; Rojanasakul, Yon/0000-0002-8839-6462 NR 42 TC 29 Z9 30 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0162-0134 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD NOV 1 PY 1994 VL 56 IS 2 BP 77 EP 86 DI 10.1016/0162-0134(94)85039-9 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA PN850 UT WOS:A1994PN85000002 PM 7798895 ER PT J AU RICHARD, G WRIGHT, AR HARRIS, S DOYLE, SZ KORGE, B MAZZANTI, C TANAKA, T HARTH, W MCBRIDE, OW COMPTON, JG BALE, SJ DIGIOVANNA, JJ AF RICHARD, G WRIGHT, AR HARRIS, S DOYLE, SZ KORGE, B MAZZANTI, C TANAKA, T HARTH, W MCBRIDE, OW COMPTON, JG BALE, SJ DIGIOVANNA, JJ TI FINE MAPPING OF THE DARIERS-DISEASE LOCUS ON CHROMOSOME 12Q SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE GENODERMATOSIS; KERATOSIS FOLLICULARIS; EPIDERMIS; LINKAGE ID REPEAT POLYMORPHISM; CELL-ADHESION; GENE; LOCALIZATION AB Darier's disease (DD) is an autosomal dominant genodermatosis characterized by epidermal acantholysis and dyskeratosis. We have performed genetic linkage studies in 10 families with DD (34 affected) by analyzing 14 polymorphic microsatellite markers. Our results confirm recent reports mapping the DD gene to chromosome 12q23-q24.1. Haplotype analysis of recombinant chromosomes in our families, along with previously, reported data, narrow the location of the DD gene to a 5 cM interval flanked by the loci D12S354 and D12S84/D12S105. This localization allowed exclusion of;two known genes, PLA2A and PAH, as candidate loci for DD. Three other gene loci (PPP1C, PMCH, PMCA1), mapping in 12q21-q24, remain potential candidates. C1 NIAMS,SKIN BIOL LAB,GENET STUDIES SECT,BETHESDA,MD. IST DERMOPATICO IMMACOLATA,ROME,ITALY. KYOTO UNIV,DEPT DERMATOL,KYOTO,JAPAN. HAUTKLIN,ERFURT,GERMANY. DCBDC,BIOCHEM LAB,BETHESDA,MD. NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NR 25 TC 10 Z9 10 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 1994 VL 103 IS 5 BP 665 EP 668 DI 10.1111/1523-1747.ep12398429 PG 4 WC Dermatology SC Dermatology GA PT439 UT WOS:A1994PT43900009 PM 7963653 ER PT J AU RUHL, KK POMIDOR, MM RHIM, JS TUAN, RS HICKOK, NJ AF RUHL, KK POMIDOR, MM RHIM, JS TUAN, RS HICKOK, NJ TI POSTTRANSCRIPTIONAL SUPPRESSION OF HUMAN ORNITHINE DECARBOXYLASE GENE-EXPRESSION BY PHORBOL ESTERS IN HUMAN KERATINOCYTES SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE TPA ID EPIDERMAL-CELL CULTURES; DNA-SYNTHESIS; 12-O-TETRADECANOYLPHORBOL 13-ACETATE; MOUSE EPIDERMIS; ENZYME PROTEIN; MESSENGER-RNA; RETINOIC ACID; INDUCTION; SKIN; GROWTH AB The induction of ornithine decarboxylase levels by the phorbol ester 12-0-tetradecanoyl-phorbol-13-acetate (TPA) in mouse skin has been shown to be integral to tumor promotion by TPA, and changes in ornithine decarboxylase activity indicate the proliferative state of many different cell types. However, in cultured human epidermal cells, TPA has been reported to be antiproliferative. Therefore, to elucidate pathways that TPA activates in cultured human skin cells, we have examined the levels at which TPA regulates ornithine decarboxylase gene expression in two immortalized human epidermal keratinocyte cell lines, and in normal neonatal keratinocytes. We have found that in cultured human keratinocytes, TPA causes a marked decrease in ornithine decarboxylase enzyme activity (50-90%), with no detectable effect on ornithine decarboxylase mRNA levels. TPA decreased steady-state levels of ornithine decarboxylase immunoreactive protein (similar to 50-67%), accounting for the 50-90% suppression of ornithine decarboxylase activity levels, as well as decreasing new synthesis of ornithine decarboxylase protein (48-50%). However, measurement of ornithine decarboxylase protein half-life showed no significant effect of TPA. Also, prolonged treatment of keratinocytes with phorbol esters abolished the suppression of ornithine decarboxylase activity by TPA. Our data, therefore, suggest that phorbol esters suppress ornithine decarboxylase gene expression predominantly by decreasing ornithine decarboxylase mRNA translatability. C1 THOMAS JEFFERSON UNIV,JEFFERSON INST MOLEC MED,DEPT DERMATOL,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON INST MOLEC MED,DEPT BIOCHEM & MOLEC BIOL,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON INST MOLEC MED,DEPT ORTHOPAED SURG,PHILADELPHIA,PA 19107. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. FU NIAMS NIH HHS [AR-41757, AR-40022] NR 36 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 1994 VL 103 IS 5 BP 687 EP 692 DI 10.1111/1523-1747.ep12398542 PG 6 WC Dermatology SC Dermatology GA PT439 UT WOS:A1994PT43900014 PM 7963658 ER PT J AU KRAEMER, KH LEVY, DD PARRIS, CN GOZUKARA, EM MORIWAKI, S ADELBERG, S SEIDMAN, MM AF KRAEMER, KH LEVY, DD PARRIS, CN GOZUKARA, EM MORIWAKI, S ADELBERG, S SEIDMAN, MM TI XERODERMA-PIGMENTOSUM AND RELATED DISORDERS - EXAMINING THE LINKAGE BETWEEN DEFECTIVE-DNA REPAIR AND CANCER SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE COCKAYNE SYNDROME; TRICHOTHIODYSTROPHY; DYSPLASTIC NEVUS SYNDROME; COMPLEMENTATION GROUPS ID NUCLEOTIDE EXCISION REPAIR; DYSPLASTIC NEVUS SYNDROME; ULTRAVIOLET MUTATIONAL SPECTRUM; CUTANEOUS MALIGNANT-MELANOMA; COCKAYNE-SYNDROME; ESCHERICHIA-COLI; PRONE DISORDER; HUMAN-CELLS; GENE ERCC6; GROUP-C AB Xeroderma pigmentosum, Cockayne syndrome, the xeroderma pigmentosum-Cockayne syndrome complex, and trichothiodystrophy cells have defects in DNA repair and are associated with clinical and cellular hypersensitivity to ultraviolet radiation (UV). Familial dysplastic nevus syndrome cells have UV hypermutability. Although xeroderma pigmentosum and dysplastic nevus syndrome have markedly increased cancer risk, Cockayne syndrome and trichothiodystrophy do not. At the molecular level, these disorders are associated with several different genetic defects as evidenced by the existence of multiple overlapping complementation groups. Recent progress has been made in identifying the chromosomal location and cloning the defective genes in these disorders. Using plasmid shuttle vectors we have shown abnormal repair and mutagenesis of DNA damaged by 254-nm (UVC) or 295-nm (UVB) radiation or the chemical carcinogen aflatoxin in cells from patients with xeroderma pigmentosum. Although xeroderma pigmentosum cells are defective in repair of all photoproducts, Cockayne syndrome cells appear to be defective in repair of cyclobutane dimers and have normal repair of nondimer photoproducts. DNS cells have post UV plasmid hypermutability. These diseases may serve as models for examining molecular mechanisms of carcinogenesis in humans. C1 OTSU PHARMACEUT, ROCKVILLE, MD USA. RP KRAEMER, KH (reprint author), NCI, MOLEC CARCINOGENESIS LAB, BLDG 37, ROOM 3E24, BETHESDA, MD 20892 USA. FU Intramural NIH HHS [Z01 BC004517-31] NR 58 TC 37 Z9 38 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 1994 VL 103 IS 5 SU S BP S96 EP S101 DI 10.1111/1523-1747.ep12399329 PG 6 WC Dermatology SC Dermatology GA PU666 UT WOS:A1994PU66600017 PM 7963692 ER PT J AU STEINERT, PM NORTH, ACT PARRY, DAD AF STEINERT, PM NORTH, ACT PARRY, DAD TI STRUCTURAL FEATURES OF KERATIN INTERMEDIATE FILAMENTS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article; Proceedings Paper CT 42nd Annual Symposium on the Biology of Skin - The Genetics of Skin Disease CY JUL 24-28, 1993 CL SNOWMASS VILLAGE, CO ID EPIDERMOLYSIS-BULLOSA SIMPLEX; COILED-COIL; ROD DOMAIN; MUTATION; INVITRO; MOLECULES; HYPERKERATOSIS; GENE; DIFFERENTIATION; HETERODIMER AB The first step in the assembly of a keratin intermediate filament (KIF) is the formation of a type I/type II heterodimer molecule in which two chains become aligned in parallel and close axial registration to form a flexible segmented alpha-helical coiled-coil rope 46 nm long. The segments of coiled-coil are interspersed by sequences that introduce irregularities of unknown structure. Here we have modeled two of these, the link L2 and the heptad discontinuity located near the middle of segment 2B. In a model for L2, the orientation of the coiled-coil structure is turned through about 180 degrees over the eight residue stretch constituting this link segment. In contrast, the heptad discontinuity in segment 2B would seem to result in only minimal distortion of the coiled-coil rope, contrary to previous expectations. Little is known about how the neighboring molecules are aligned and packed within the assembled KIF. Crosslinking experiments with KIF have determined that two neighboring molecules are aligned antiparallel and axially in three ways, and predict that similarly-directed molecules could be overlapped by about 1 nm. The two-dimensional surface lattice resulting from these data predicts an axial periodicity of 22.6 nm, which in fact is visible by electron microscopy of shadowed KIF. Interestingly, most of the amino acid substitutions resulting from mutations in the keratin genes found in genodermatoses are clustered in this molecular overlap region. Although we do not yet know how the rows of antiparallel molecules fold in three dimensions to form an intact KIF, certain of the observed crosslinks could also occur between nearest neighbor parallel molecules across a four-molecule strand; that is, KIF may be built from bundles or protofibrils. These insights on molecular structure and molecular packing provide new constraints on models for KIF structure. C1 NIAMSD,SKIN BIOL BRANCH,BETHESDA,MD 20892. UNIV LEEDS,DEPT BIOCHEM & MOLEC BIOL,LEEDS LS2 9JT,W YORKSHIRE,ENGLAND. MASSEY UNIV,DEPT PHYS & BIOPHYS,PALMERSTON NORTH,NEW ZEALAND. NR 45 TC 51 Z9 51 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 1994 VL 103 IS 5 SU S BP S19 EP S24 DI 10.1111/1523-1747.ep12398900 PG 6 WC Dermatology SC Dermatology GA PU666 UT WOS:A1994PU66600005 PM 7525737 ER PT J AU YUSPA, SH DLUGOSZ, AA CHENG, CK DENNING, MF TENNENBAUM, T GLICK, AB WEINBERG, WC AF YUSPA, SH DLUGOSZ, AA CHENG, CK DENNING, MF TENNENBAUM, T GLICK, AB WEINBERG, WC TI ROLE OF ONCOGENES AND TUMOR-SUPPRESSOR GENES IN MULTISTAGE CARCINOGENESIS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article; Proceedings Paper CT 42nd Annual Symposium on the Biology of Skin - The Genetics of Skin Disease CY JUL 24-28, 1993 CL SNOWMASS VILLAGE, CO ID MOUSE SKIN CARCINOGENESIS; PROTEIN-KINASE-C; TRANSFORMING GROWTH-FACTOR; HARVEY-RAS GENE; HUMAN PAPILLOMAVIRUS TYPE-16; CULTURED EPIDERMAL-CELLS; V-HA-RAS; TERMINAL DIFFERENTIATION; MALIGNANT CONVERSION; MURINE KERATINOCYTES AB The introduction of the techniques of molecular biology as tools to study skin carcinogenesis has provided more precise localization of biochemical pathways that regulate the tumor phenotype. This approach has identified genetic changes that are characteristic of each of the specific stages of squamous cancer pathogenesis: initiation, exogenous promotion, premalignant progression, and malignant conversion. Initiation can result from mutations in a single gene, and the Harvey allele of the ras gene family has been identified as a frequent site for initiating mutations. Heterozygous activating mutations in c-ras(Ha) are dominant, and affected keratinocytes hyperproliferate and are resistant to signals for terminal differentiation. An important pathway impacted by c-ras(Ha) activation is the protein kinase C (PKC) pathway, a major regulator of keratinocyte differentiation. Increased activity of PKC alpha and suppression of PKC delta by tyrosine phosphorylation contribute to the phenotypic consequences of ras(Ha) gene activation in keratinocytes. Tumor promoters disturb epidermal homeostasis and cause selective clonal expansion of initiated cells to produce multiple benign squamous papillomas. Resistance to differentiation and enhanced growth rate of initiated cells impart a growth advantage when the epidermis is exposed to promoters. The frequency of premalignant progression varies among papillomas, and subpopulations at high risk for progression have been identified. These high-risk papillomas overexpress the alpha 6 beta 4 integrin and are deficient in transforming growth factor beta 1 and beta 2 peptides, two changes associated with a very high proliferation rate in this subset of tumors. The introduction of an oncogenic ras(Ha) gene into epidermal cells derived from transgenic mice with a null mutation in the TGF beta 1 gene have an accelerated rate of malignant progression when examined in vivo. Thus members of the TGF beta gene family contribute a tumor-suppressor function in carcinogenesis. Accelerated malignant progression is also found with v-ras(Ha) transduced keratinocytes from skin of mice with a null mutation in the p53 gene. The similarities in risk for malignant conversion by initiated keratinocytes from TG beta 1 and p53 null geneotypes suggest that a common, growth-related pathway may underly the tumor-suppressive functions of these proteins in the skin carcinogenesis model RP YUSPA, SH (reprint author), NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BLDG 37,ROOM 3B25,BETHESDA,MD 20892, USA. RI Weinberg, Wendy/A-8920-2009 NR 90 TC 54 Z9 54 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 1994 VL 103 IS 5 SU S BP S90 EP S95 DI 10.1111/1523-1747.ep12399255 PG 6 WC Dermatology SC Dermatology GA PU666 UT WOS:A1994PU66600016 PM 7963691 ER PT J AU LEWIN, AH LAMB, PB POPIK, P SKOLNICK, P AF LEWIN, AH LAMB, PB POPIK, P SKOLNICK, P TI ONE-STEP PREPARATION OF [2,3-H-3]1-AMINOCYCLOPROPANECARBOXYLIC ACID - A USEFUL LIGAND FOR STRYCHNINE-INSENSITIVE GLYCINE RECEPTORS SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE 1-AMINOCYCLOPROPANECARBOXYLIC ACID; GLYCINE; STRYCHNINE-INSENSITIVE; RADIOLIGAND; TRITIATED; H-3 NMR ID XENOPUS OOCYTES; CARBOXYLIC-ACID; SITE; ACTIVATION; ACC AB Catalytic hydrogenation of 1-aminocyclopropenecarboxylic acid under tritium gas afforded [2,3-H-3]1-aminocyclopropanecarboxylic acid with specific activity 26 Ci/mmol, determined by a combination of H-1 and H-3 NMR. Pilot radioligand binding assays indicate this compound will be a useful probe for the NMDA receptor-associated strychnine-insensitive glycine receptor. C1 NIDDK,NEUROSCI LAB,BETHESDA,MD 20892. RP LEWIN, AH (reprint author), RES TRIANGLE INST,POB 12194,RES TRIANGLE PK,NC 27709, USA. RI Popik, Piotr/R-5383-2016 OI Popik, Piotr/0000-0003-0722-1263 NR 8 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD NOV PY 1994 VL 34 IS 11 BP 1063 EP 1068 DI 10.1002/jlcr.2580341109 PG 6 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA PQ124 UT WOS:A1994PQ12400008 ER PT J AU PAWLOSKY, R BARNES, A SALEM, N AF PAWLOSKY, R BARNES, A SALEM, N TI ESSENTIAL FATTY-ACID METABOLISM IN THE FELINE - RELATIONSHIP BETWEEN LIVER AND BRAIN PRODUCTION OF LONG-CHAIN POLYUNSATURATED FATTY-ACIDS SO JOURNAL OF LIPID RESEARCH LA English DT Article DE DOMESTIC FELINES; DOCOSAHEXAENOIC ACID; ARACHIDONIC ACID; DEUTERIUM-LABELED LINOLEIC AND LINOLENIC ACIDS; GC-MS; DESATURATION ID DOCOSAHEXAENOIC ACID; RAT RETINAS; CAT; DEFICIENCY AB A comparison was made between the liver and brain conversion of linoleic acid, 18:2n-6, and linolenic acid, 18:3n-3, to long chain polyunsaturated fatty acids in domestic felines. This report demonstrates that 6-desaturase activity does exist in the feline. The liver produced deuterium-labeled polyunsaturated fatty acids up to 22:4n-6 and 22:5n-3. The brain was found to accumulate the deuterium-labeled polyunsaturated fatty acids, 22:5n-6, 22:6n-3, 24:4n-6, 24:5n-6, 24:5n-3, and 24:6n-3. Adult felines were provided a diet consisting of either 10% fat (hydrogenated coconut oil-corn oil 9:1) containing no 20- or 22-carbon n-6 or n-3 fatty acids or a chow diet with meat and meat by-products that contained these long chain polyunsaturated fatty acids for a 6-month period. During this time, the in vivo production of long chain polyunsaturated fatty acids was evaluated in these animals. The cats were given oral doses of both [17,17,18,18,18-H-2]18:3n-3 and [9,10,12,13-H-2]18:2n-6 and the deuterium-labeled fatty acid metabolites were measured in the blood, liver, and brain using a highly sensitive and specific gas chromatography-mass spectrometry technique. Contrary to previous claims, 6-desaturase activity was shown to exist in the feline. The evidence for this was the detection of [9,10,12,13-H-2] 18:3n-6 which was converted from [9,10,12,13-H-2]18:2n-6 and observed in the plasma. For the first time, direct evidence for the metabolism of n-3 fatty acids in cats was obtained by the detection of deuterium-labeled metabolites including the polyunsaturated fatty acid, 22:5n-3, in the plasma, following an oral dose of deuterium-labeled 18:3n-3. The more highly unsaturated deuterium-labeled 22- and 24-carbon fatty acids including: 22:6n-3, 24:5n-3, 24:6n-3, 22:5n-6, 24:4n-6, and 24:5n-6 accumulated in the nervous system. These deuterium-labeled fatty acids were not detected in either the liver or plasma. As the liver was found to produce and export into the blood the deuterium-labeled 22:5n-3 and 22:4n-6, it is suggested that these intermediates are then transported to the brain and retina where they are converted to 22:6n-3 and 22:5n-6, respectively. This route for the accretion of 22:6n-3 in the nervous system has not been previously proposed. In the feline, it appears that both the liver and the brain are involved in biosynthesizing long-chain polyunsaturated fatty acids when no preformed 20- and 22-carbon essential fatty acids are present in the diet. C1 NIAAA,DIV INTRAMURAL CLIN & BIOL RES,MEMBRANE BIOCHEM & BIOPHYS LAB,ROCKVILLE,MD 20852. NR 18 TC 83 Z9 84 U1 1 U2 2 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD NOV PY 1994 VL 35 IS 11 BP 2032 EP 2040 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PR230 UT WOS:A1994PR23000013 PM 7868981 ER PT J AU CECKLER, TL BALABAN, RS AF CECKLER, TL BALABAN, RS TI FIELD DISPERSION IN WATER-MACROMOLECULAR PROTON MAGNETIZATION-TRANSFER SO JOURNAL OF MAGNETIC RESONANCE SERIES B LA English DT Note ID PROTEIN SOLUTIONS; CROSS-RELAXATION; TISSUES RP CECKLER, TL (reprint author), NHLBI,BLDG 1,ROOM B3-07,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 29 TC 19 Z9 19 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 1064-1866 J9 J MAGN RESON SER B JI J. Magn. Reson. Ser. B PD NOV PY 1994 VL 105 IS 3 BP 242 EP 248 DI 10.1006/jmrb.1994.1131 PG 7 WC Physics, Atomic, Molecular & Chemical SC Physics GA QB822 UT WOS:A1994QB82200006 PM 7850170 ER PT J AU DAI, JR DECOSTERD, LA GUSTAFSON, KR CARDELLINA, JH GRAY, GN BOYD, MR AF DAI, JR DECOSTERD, LA GUSTAFSON, KR CARDELLINA, JH GRAY, GN BOYD, MR TI NOVEL NAPHTHOQUINONES FROM CONOSPERMUM-INCURVUM SO JOURNAL OF NATURAL PRODUCTS-LLOYDIA LA English DT Article ID HIV AB During the reisolation of the trimeric naphthoquinone derivative conocurvone [1] from an extract of the Australian shrub Conospermum incurvum, six monomeric naphthoquinones were isolated. These include three novel 1,4-naphthoquinone derivatives: 3-methyl-14,15-dihydro-15-hydroxyteretifolione B [3], 3-methyl-14,15-dihydro-15-hydroxyteretifolione B methyl ether [4], and 2,3-dimethyl-6-hydroxy-7-methoxy-1,4-naphthoquinone C51. In addition, the previously reported compounds 3-methylteretifolione B [6], 3-methylteretifolione B methyl ether [7], and 8-geranyl-2,7-dihydroxy-3-methyl-1,4-naphthoquinone [8] were isolated and identified. The structures of the novel 1,4-naphthoquinones were elucidated by spectral methods. While conocurvone [1] is a potent inhibitor of HIV-1-induced cell killing, all of the monomeric naphthoquinone derivatives were inactive against HIV-1. C1 NCI,DIV CANC TREATMENT,DRUG DISCOVERY RES & DEV LAB,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. NR 6 TC 12 Z9 13 U1 0 U2 3 PU AMER SOC PHARMACOGNOSY PI CINCINNATI PA LLOYD LIBRARY & MUSEUM 917 PLUM ST, CINCINNATI, OH 45202 SN 0163-3864 J9 J NAT PRODUCTS JI J. Nat. Prod. PD NOV PY 1994 VL 57 IS 11 BP 1511 EP 1516 DI 10.1021/np50113a006 PG 6 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA PZ035 UT WOS:A1994PZ03500006 PM 7853001 ER PT J AU KAPLAN, DR STEPHENS, RM AF KAPLAN, DR STEPHENS, RM TI NEUROTROPHIN SIGNAL-TRANSDUCTION BY THE TRK RECEPTOR SO JOURNAL OF NEUROBIOLOGY LA English DT Review DE TRK; NERVE GROWTH FACTOR; NEUROTROPHIN; SIGNAL TRANSDUCTION ID NERVE GROWTH-FACTOR; PC12 PHEOCHROMOCYTOMA CELLS; INDUCED TYROSINE PHOSPHORYLATION; MICROTUBULE-ASSOCIATED PROTEIN-2; FACTOR-INDUCED DIFFERENTIATION; AFFINITY NGF BINDING; PHOSPHATIDYLINOSITOL 3-KINASE; PROTOONCOGENE PRODUCT; KINASE-ACTIVITY; MAP KINASE AB The initial event in the neuronal differentiation of PC12 cells is the binding of the neurotrophin nerve growth factor (NGF) to the Trk receptor. This interaction stimulates the intrinsic tyrosine kinase activity of Trk, initiating a signalling cascade involving the phosphorylation of intracellular proteins on tyrosine, serine, and threonine residues. These signals are then in turn propagated to other messengers, ultimately leading to differentiation, neurotrophin-dependent-survival, and the loss of proliferative capacity. To transmit NGF signals, NGF-activated Trk rapidly associates with the cytoplasmic proteins, SHC, PI-3 kinase, and PLC-gamma 1. These proteins are involved in stimulating the formation of various second messenger molecules and activating the Ras signal transduction pathway. Studies with Trk mutants indicate that the activation of the Ras pathway is necessary for complete differentiation of PC12-derived cells and for the maintenance of the differentiated phenotype. Trk also induces the tyrosine phosphorylation of SNT, a specific target of neurotrophic factor activity in neuronal cells. This review will discuss the potential roles of Trk and the proteins of the Trk signalling pathways in NGF function, and summarize our attempts to understand the mechanisms used by Trk to generate the many phenotypic responses of PC12 cells to NGF. (C) 1994 John Wiley & Sons, Inc. RP KAPLAN, DR (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MMCL,EUKARYOT SIGNAL TRANSDUCT SECT,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101] NR 98 TC 454 Z9 458 U1 1 U2 10 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD NOV PY 1994 VL 25 IS 11 BP 1404 EP 1417 DI 10.1002/neu.480251108 PG 14 WC Neurosciences SC Neurosciences & Neurology GA PL684 UT WOS:A1994PL68400007 PM 7852994 ER PT J AU SAVION, S ODDO, S GROVER, S CASPI, RR AF SAVION, S ODDO, S GROVER, S CASPI, RR TI UVEITOGENIC T-LYMPHOCYTES IN THE RAT - PATHOGENICITY VS LYMPHOKINE PRODUCTION, ADHESION MOLECULES AND SURFACE-ANTIGEN EXPRESSION SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE UVEORETINITIS; EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; PATHOGENICITY; LYMPHOKINES; ADHESION MOLECULES; SURFACE ANTIGENS ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; TUMOR-NECROSIS-FACTOR; DIFFERENT RETINAL ANTIGENS; MYELIN BASIC-PROTEIN; GROWTH-FACTOR-BETA; CELL CLONES; HELPER LYMPHOCYTES; ADOPTIVE TRANSFER; BINDING PROTEIN AB A possible correlation between the pathogenicity of autoimmune T cells and their lymphokine production, expression of functional adhesion molecules and expression of some surface antigens was examined. We used four retinal antigen-specific Lewis rat T cell lines and sublines: one specific to the major pathogenic epitope of the human retinal soluble antigen (S-Ag; residues 337-356), and three specific to the major pathogenic epitope of the bovine interphotoreceptor retinoid binding protein (IRBP; residues 1177-1191). The lines have different degrees of uveitogenicity, from highly pathogenic to nonpathogenic. All four T cell lines produced roughly equivalent amounts of interferon-gamma, lymphotoxin/tumor necrosis factor (TNF alpha/beta>), interleukin-3, interleukin-6 and transforming growth factor-beta. Interleukin-4 activity could not be detected. The lines also expressed similar levels of functional adhesion molecules, as measured by binding to cultured rat aorta endothelial cells. The nonpathogenic subline, however, was the lowest responder to antigenic stimulation with respect to proliferation and interleukin-2 production. Examination of eel surface antigens showed that in contrast to the other lines, the majority of cells in the nonpathogenic subline lacked detectable expression of CD4. No difference was found in the level of expression of the IL-2 receptor and T cell antigen receptor among the four lines. Because CD4 is the restricting element in these lines, reduced CD4 expression in the nonpathogenic subline may at least partially explain its poor response in vitro to antigenic stimulation. All three attributes could be connected to lack of pathogenicity of this line in vivo. These results support the contention that class II-restricted recognition of autoantigen within the neuroretina by uveitogenic T lymphocytes must occur as an initial step in the pathogenesis of EAU. A defect in this step will preclude pathogenesis regardless of some other functional attributes possessed by effector T cells, such as production of inflammatory lymphokines and expression of adhesion molecules. C1 NEI,IMMUNOL LAB,BETHESDA,MD 20892. NR 46 TC 24 Z9 24 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD NOV PY 1994 VL 55 IS 1 BP 35 EP 44 DI 10.1016/0165-5728(94)90144-9 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA PV319 UT WOS:A1994PV31900004 PM 7525641 ER PT J AU HAXBY, JV HORWITZ, B UNGERLEIDER, LG MAISOG, JM PIETRINI, P GRADY, CL AF HAXBY, JV HORWITZ, B UNGERLEIDER, LG MAISOG, JM PIETRINI, P GRADY, CL TI THE FUNCTIONAL-ORGANIZATION OF HUMAN EXTRASTRIATE CORTEX - A PET-RCBF STUDY OF SELECTIVE ATTENTION TO FACES AND LOCATIONS SO JOURNAL OF NEUROSCIENCE LA English DT Article DE EXTRASTRIATE CORTEX; HUMAN; OBJECT VISION; SPATIAL VISION; NEUROIMAGING; CEREBRAL BLOOD FLOW ID POSITRON-EMISSION TOMOGRAPHY; HUMAN VISUAL-CORTEX; POSTERIOR PARIETAL CORTEX; RHESUS-MONKEY; EVOKED-POTENTIALS; BRAIN; IMAGES; CONNECTIONS; OBJECT; AREAS AB The functional dissociation of human extrastriate cortical processing streams for the perception of face identity and location was investigated in healthy men by measuring visual task-related changes in regional cerebral blood flow (rCBF) with positron emission tomography (PET) and H-2 O-15. Separate scans were obtained while subjects performed face matching, location matching, or sensorimotor control tasks. The matching tasks used identical stimuli for some scans and stimuli of equivalent visual complexity for others. Face matching was associated with selective rCBF increases in the fusiform gyrus in occipital and occipitotemporal cortex bilaterally and in a right prefrontal area in the inferior frontal gyrus. Location matching was associated with selective rCBF increases in dorsal occipital, superior parietal, and intraparietal sulcus cortex bilaterally and in dorsal right premotor cortex. Decreases in rCBF, relative to the sensorimotor control task, were observed for both matching tasks in auditory, auditory association, somatosensory, and midcingulate cortex. These results suggest that, within a sensory modality, selective attention is associated with increased activity in those cortical areas that process the attended information but is not associated with decreased activity in areas that process unattended visual information. Selective attention to one sensory modality, on the other hand, is associated with decreased activity in cortical areas dedicated to processing input from other sensory modalities. Direct comparison of our results with those from other PET-rCBF studies of extrastriate cortex demonstrates agreement in the localization of cortical areas mediating face and location perception and dissociations between these areas and those mediating the perception of color and motion. C1 NIA, NEUROSCI LAB, BETHESDA, MD USA. NIMH, NEUROPSYCHOL LAB, BETHESDA, MD 20892 USA. RP HAXBY, JV (reprint author), NIMH, PSYCHOL & PSYCHOPATHOL LAB, FUNCT BRAIN IMAGING SECT,BLDG 10, ROOM 4C110, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 42 TC 829 Z9 836 U1 1 U2 28 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV PY 1994 VL 14 IS 11 BP 6336 EP 6353 PN 1 PG 18 WC Neurosciences SC Neurosciences & Neurology GA PQ381 UT WOS:A1994PQ38100004 PM 7965040 ER PT J AU EVERSON, CA SMITH, CB SOKOLOFF, L AF EVERSON, CA SMITH, CB SOKOLOFF, L TI EFFECTS OF PROLONGED SLEEP-DEPRIVATION ON LOCAL-RATES OF CEREBRAL ENERGY-METABOLISM IN FREELY MOVING RATS SO JOURNAL OF NEUROSCIENCE LA English DT Article DE SLEEP DEPRIVATION; BRAIN; GLUCOSE UTILIZATION; WHOLE-BODY METABOLISM; AUTORADIOGRAPHY; DEOXYGLUCOSE; BRAIN TEMPERATURE ID CENTRAL NERVOUS-SYSTEM; GLUCOSE-UTILIZATION; CYTOKINES; BRAIN; TEMPERATURE; RECOVERY AB Although sleep deprivation interferes with biological processes essential for performance, health, and longevity, previous studies have failed to reveal any structural or functional changes in brain. We have therefore measured local rates of cerebral glucose utilization (ICMR(glc)) with the quantitative autoradiographic 2-C-14-deoxyglucose method in an effort to determine if and, if so, where sleep deprivation might affect function in sleep-deprived rats. Sleep deprivation was maintained for 11-12 d, long enough to increase whole body energy metabolism, thus confirming that pathophysiological processes that might involve brain functions were evolving. Deep brain temperature was also measured in similarly treated rats and found to be mildly elevated relative to core body temperature. Despite the increased deep brain temperature, systemic hypermetabolism, and sympathetic activation, ICMR(glc) was not elevated in any of the 60 brain structures examined. Average glucose utilization in the brain as a whole was unchanged in the sleep-deprived rats, but regional decreases were found. The most marked decreases in ICMR(glc) were in regions of the hypothalamus, thalamus, and limbic system. Mesencephalic and pontine regions were relatively unaffected except for the central gray area. The medulla was entirely normal. The effects of sleep deprivation on brain tended, therefore, to be unidirectional toward decreased energy metabolism, primarily in regions associated with mechanisms of thermoregulation, endocrine regulation, and sleep. Correspondence was found between the hypometabolic brain regions and some aspects of peripheral symptoms. C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. RP EVERSON, CA (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,BLDG 10,ROOM 4S-239,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 54 TC 56 Z9 57 U1 3 U2 4 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 NOV PY 1994 VL 14 IS 11 BP 6769 EP 6778 PN 2 PG 10 WC Neurosciences SC Neurosciences & Neurology GA PQ382 UT WOS:A1994PQ38200001 PM 7965078 ER PT J AU KOLACHANA, BS SAUNDERS, RC WEINBERGER, DR AF KOLACHANA, BS SAUNDERS, RC WEINBERGER, DR TI AN IMPROVED METHODOLOGY FOR ROUTINE IN-VIVO MICRODIALYSIS IN NONHUMAN-PRIMATES SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE DIALYSIS; MAGNETIC RESONANCE IMAGING; STEREOTAXY; DOPAMINE; GUIDE HOLDER ID MONKEYS; BRAIN AB A new method was developed to carry out in vivo microdialysis experiments repetitively and routinely within an individual monkey. We designed and built a dialysis probe guide and holding device ('guide holder') which permits accurate placement of dialysis probes into cortical (e.g., prefrontal, hippocampus, and parietal cortices) and subcortical target areas (e.g., caudate nucleus, amygdala, and nucleus accumbens) of the rhesus monkey brain without extensive and repetitive surgery needed to expose a desired brain region. The guide holder is positioned, using MRI-guided coordinates, and fixed to the skull over an intended targeted region. This design provides an opportunity to conduct several experiments in a single monkey over an extended period and permits placement of several probes accurately into 'fresh' or 'experienced' tissue during repeated microdialysis experiments. In addition, during repeated dialysis experiments tissue trauma is minimized because no surgical procedure is necessary on the day of dialysate collection. This procedure can be readily adapted for use with an awake monkey. C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,IRP,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NR 14 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD NOV PY 1994 VL 55 IS 1 BP 1 EP 6 DI 10.1016/0165-0270(94)90033-7 PG 6 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA PU635 UT WOS:A1994PU63500001 PM 7891457 ER PT J AU OLAH, Z LEHEL, C ANDERSON, WB BRENNEMAN, DE VONAGOSTON, D AF OLAH, Z LEHEL, C ANDERSON, WB BRENNEMAN, DE VONAGOSTON, D TI SUBNANOMOLAR CONCENTRATION OF VIP INDUCES THE NUCLEAR TRANSLOCATION OF PROTEIN-KINASE-C IN NEONATAL RAT CORTICAL ASTROCYTES SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE VIP; PROTEIN KINASE C; ISOZYMES; NUCLEAR; TRANSLOCATION ID VASOACTIVE-INTESTINAL-PEPTIDE; SWISS 3T3 CELLS; IMMUNOCHEMICAL CHARACTERIZATION; HEMATOPOIETIC-CELLS; NEURONAL SURVIVAL; CEREBRAL-ISCHEMIA; NIH-3T3 CELLS; GROWTH-FACTOR; LIVER NUCLEI; EXPRESSION AB At subnanomolar concentrations, vasoactive intestinal peptide (VIP) can act as an astroglial mitogen and as a secretagogue for neurotrophic substances released from glia (Brenneman et al.: J Neurosci Res 25:386-394, 1990), Here we report that treatment with subnanomolar (0.1 nM) VIP, that does not produce an increase in intracellular cAMP levels, induced the translocation of protein kinase C (PKC) from the cytoplasm to the nucleus in neonatal cortical astrocytes, as revealed by immunohistochemistry, Western blot analysis, and measurements of the enzyme activity, Western blot analysis of subcellular fractions, using PKC isotype-specific antisera, showed PKC alpha as well as the two novel PKC isotypes, delta and zeta immunoreactivities, whereas PKC beta or gamma immunoreactivities were not detected, PKC alpha was associated predominantly with the cytosolic compartment, while PKC delta was found in the plasma membrane and in nuclear fractions. In contrast, PKC zeta was distributed ubiquitously within the major subcellular fractions. Treatment of the cells with 0.1 nM VIP caused a marked increase in nuclear PKC alpha and, to a lesser extent, PKC delta and PKC zeta immunoreactivities. Western blot analysis showed that a low (1 nM) concentration of phorbol, 12-myristate, 13 acetate also caused the subcellular redistribution of PKC immunoreactivities from the cytoplasm to the nuclear fraction, similar to VIP treatment. Exposure of astrocytes to high concentrations (1 mu M) of phorbol, 12-myristate, 13 acetate resulted in the down-regulation of PKC alpha and PKC delta, while distribution of PKC zeta immunoreactivities were only slightly altered. Measurements of Ca2+ - and phospholipid-dependent PKC activities also showed a VIP-induced redistribution of PKC activity from the cytoplasmic to the nuclear fractions. These results suggest that PKC may be involved in the signal transduction process elicited by VIP binding to the high affinity VIP receptors present on cortical astrocytes. The observed changes in the nuclear localization of PKC alpha and PRC delta in response to subnanomolar VIP may play a role in mediating the cellular response(s) to this peptide during neurodevelopment. (C) 1994 Wiley-Liss, Inc.* C1 NICHHD,MOLEC & DEV PHARMACOL SECT,BETHESDA,MD. NICHHD,MOLEC CONTROL NEURODIFFERENTIAT SECT,DEV NEUROBIOL LAB,BETHESDA,MD. RP OLAH, Z (reprint author), NCI,CELLULAR ONCOL LAB,BLDG 37,ROOM 1E14,BETHESDA,MD 20892, USA. NR 43 TC 46 Z9 47 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD NOV 1 PY 1994 VL 39 IS 4 BP 355 EP 363 DI 10.1002/jnr.490390402 PG 9 WC Neurosciences SC Neurosciences & Neurology GA QM215 UT WOS:A1994QM21500001 PM 7884816 ER PT J AU RUFER, M FLANDERS, K UNSICKER, K AF RUFER, M FLANDERS, K UNSICKER, K TI PRESENCE AND REGULATION OF TRANSFORMING GROWTH-FACTOR-BETA MESSENGER-RNA AND PROTEIN IN THE NORMAL AND LESIONED RAT SCIATIC-NERVE SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE TGF-BETA REGULATION; PERIPHERAL NERVE LESION; SCHWANN CELL; NERVE REGENERATION ID CULTURED SCHWANN-CELLS; WALLERIAN DEGENERATION; EXPRESSION; LOCALIZATION; SYSTEM; FACTOR-BETA-1; FIBRONECTIN; TGF-BETA-1; INJURY; PARTICIPATION AB The transforming growth factors beta (TGF-beta), a family of regulatory polypeptides, are involved in numerous vital processes including inflammation and wound healing. Since repair of a peripheral nerve lesion includes a series of well-defined steps of cellular actions possibly controlled by TGF-beta s, and since TGF-beta mRNA and immunoreactivity have been found in the normal peripheral nerve, we have examined TGF-beta mRNA regulation and protein expression in the lesioned peripheral nerve. Sciatic nerves of adult rats were either crushed (allowing axonal regeneration) or transected (to prevent axonal regeneration and to induce Wallerian degeneration in the distal stump). After intervals of 6 hours, 2 and 6 days post-lesion, the rats were sacrificed and each nerve was cut into four segments, two proximal and two distal to the lesion site. TGF-beta 1-3 mRNA were determined for each segment. We demonstrate that TGF-beta 1 mRNA levels are higher than those of TGF-beta 3; the amplitude of mRNA regulation depends on time, type of lesion and localization relative to the lesion site. TGF-beta 2 mRNA could not be detected. For TGF-beta 1-3 immunocytochemistry, animals were sacrificed 12, 24, 48, 72 hours and 7 and 14 days after surgery. TGF-beta immunoreactivity (IR) was observed for all isoforms in lesioned and unlesioned nerves. In the segment directly adjacent to the lesion at its proximal side, an increase of TGF-beta-IR became apparent as soon as 12 hours after surgery; it remained elevated during the whole period observed in both models. In the segment adjoining the distal side of the lesion, an increase of TGF-beta-IR was observed after 48 hours, which was still present after 14 days. At day 7 after crush or transection, an increase of TGF-beta-IR was detected in the most distal segments, which reached its highest levels at the end of our observation period. Our results suggest that the presence of axonal contact might induce an enhancement of TGF-beta expression by Schwann cells in the distal stump of a lesioned and regenerating peripheral nerve. Since we demonstrate an increase of TGF-beta mRNA and protein expression also in the distal stump of transected nerves where Schwann cells are not able to contact sprouting axons from the proximal part, other regulatory pathways must exist. The acquisition of a ''reactive'' Schwann cell phenotype after peripheral nerve lesion might involve an upregulation of TGF-beta expression. (C) 1994 Wiley-Liss, Inc. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. RP RUFER, M (reprint author), UNIV HEIDELBERG,DEPT ANAT & CELL BIOL 3,NEUENHEIMER FELD 307,D-69120 HEIDELBERG,GERMANY. NR 54 TC 50 Z9 53 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD NOV 1 PY 1994 VL 39 IS 4 BP 412 EP 423 DI 10.1002/jnr.490390408 PG 12 WC Neurosciences SC Neurosciences & Neurology GA QM215 UT WOS:A1994QM21500007 PM 7884820 ER PT J AU OLDFIELD, EH AF OLDFIELD, EH TI CHIARI-I AND SYRINGOMYELIA - RESPONSE SO JOURNAL OF NEUROSURGERY LA English DT Letter RP OLDFIELD, EH (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD NOV PY 1994 VL 81 IS 5 BP 812 EP 813 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA PN296 UT WOS:A1994PN29600041 ER PT J AU MAZZOTTA, G PACE, L BONOW, RO AF MAZZOTTA, G PACE, L BONOW, RO TI RISK STRATIFICATION OF PATIENTS WITH CORONARY-ARTERY DISEASE AND LEFT-VENTRICULAR DYSFUNCTION BY EXERCISE RADIONUCLIDE ANGIOGRAPHY AND EXERCISE ELECTROCARDIOGRAPHY SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE CORONARY ARTERY DISEASE; LEFT VENTRICULAR DYSFUNCTION; EXERCISE-INDUCED ISCHEMIA ID MILDLY SYMPTOMATIC PATIENTS; MEDICALLY TREATED PATIENTS; EJECTION FRACTION; NONINVASIVE IDENTIFICATION; BYPASS-SURGERY; SURVIVAL; REST; ARRHYTHMIAS; PROGNOSIS; ISCHEMIA AB Background. The results of multicenter trials indicate that patients with left ventricular dysfunction and either three-vessel or left main coronary artery disease have improved prognosis when treated surgically. Objective. As part of a larger evaluation and follow-up study of coronary artery disease, the objective of this investigation was to determine whether exercise radionuclide angiography can be used, in patients with mild symptoms of coronary artery disease and left ventricular dysfunction at rest, to identify patients with three-vessel or left main coronary artery disease. Methods and Results. Eighty-four consecutive patients were studied with angiographically defined coronary artery disease in whom left ventricular ejection fraction at rest ranged from 20% to 40%. Patients underwent exercise electrocardiography, rest and exercise radionuclide angiography, and 24-hour electrocardiographic monitoring. There were 22 patients with one-vessel, 31 with two-vessel, 27 with three-vessel, and four with left main coronary artery disease. All but four patients had a documented history of myocardial infarction. By univariate analysis, the following parameters were related to the anatomic severity of coronary artery disease: magnitude of ST segment depression with exercise (p < 0.001), magnitude of change in ejection fraction with exercise (p < 0.005), and occurrence of angina during exercise (p < 0.005). However, because of the extensive overlap among anatomic subgroups, no single factor had both a satisfactory sensitivity and a satisfactory specificity in identifying patients with three-vessel and left main coronary artery disease. Multivariate stepwise regression analysis also failed to predict three-vessel or left main coronary artery disease satisfactorily (sensitivity 73% and specificity 73%; positive predictive accuracy 59% and negative predictive accuracy 83%). Nonetheless, this multivariate analysis provided important prognostic information. During medical therapy (mean follow-up 56 months), the patients with a high likelihood of three-vessel or left main coronary artery disease had a greater risk of death or reinfarction than had patients with a low likelihood (p < 0.05). These functional data were better than coronary anatomy alone in providing risk stratification. Four of six patients with two-vessel disease who died were classified incorrectly by the multivariate analysis in the high-likelihood group for three-vessel or left main coronary artery disease, but classified correctly as being at high risk; whereas none of the patients with three-vessel disease who were misclassified in the low-likelihood group died during medical therapy. Conclusion. Although exercise radionuclide angiography in patients with minimal symptoms of coronary artery disease and left ventricular dysfunction is not precise in predicting three-vessel or left main coronary artery disease, it provides important functional information regarding subsequent prognosis during medical therapy. C1 NHLBI, CARDIOL BRANCH, BETHESDA, MD 20892 USA. OI Pace, Leonardo/0000-0002-5741-543X NR 37 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 EI 1532-6551 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD NOV-DEC PY 1994 VL 1 IS 6 BP 529 EP 536 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA PX353 UT WOS:A1994PX35300006 PM 9420747 ER PT J AU KINUYA, S JEONG, JM GARMESTANI, K SAGA, T CAMERA, L BRECHBIEL, MW GANSOW, OA CARRASQUILLO, JA NEUMANN, RD PAIK, CH AF KINUYA, S JEONG, JM GARMESTANI, K SAGA, T CAMERA, L BRECHBIEL, MW GANSOW, OA CARRASQUILLO, JA NEUMANN, RD PAIK, CH TI EFFECT OF METABOLISM ON RETENTION OF INDIUM-111-LABELED MONOCLONAL-ANTIBODY IN LIVER AND BLOOD SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE IN-111-MAB DTPA CONJUGATES; METABOLISM ID EPIDERMOID CARCINOMA XENOGRAFTS; T-CELL LYMPHOMA; COMPARATIVE BIODISTRIBUTION; ATHYMIC MOUSE; NORMAL TISSUE; NUDE-MICE; IN-111; TUMOR; DTPA; DERIVATIVES AB The effect of a chelator structure on the metabolic fate of the In-111-labeled monoclonal antibody (Mab) T101 was investigated in normal Balb/c mice to assess the importance of this chemical parameter in the reduction of the background radioactivity in blood and liver. Methods: Mab T101 was conjugated with either 2-(p-isothiocyanatobenzyl)-6-methyl-diethylaminetriaminepentaacetic acid (DTPA) (1B4M), 2-(p-isothiocyanatobenzyl) cyclohexyl-DTPA (CHX-B) or cyclic DTPA dianhydride (cDTPA) and then radiolabeled with In-111. Normal mice were injected intravenously with these In-111-labeled T101 conjugates and sacrificed in groups of five up to 5 days postinjection for comparative biodistribution studies and analyses of liver, blood and urine samples for radioindium products. Results: The biodistribution of In-111-1 B4M-T101 and In-111-CHX-B-T101 were similar to each other but significantly different from that of In-111-cDTPA-T101, particularly in the blood and liver. Size-exclusion high-performance liquid chromatography indicated that the concentration of the intact In-111-immunoglobulin (Ig)G in liver decreased with similar rates for the three conjugates. Meanwhile, the concentration of a small DTPA-like metabolite in liver increased to a different peak value (4.6% ID/g for the cDTPA conjugate and 1.6% ID/g for the 1B4M and CHX-B conjugates) approximately at 24 hr and maintained a steady-state concentration up to 5 days. Conclusion: The thiourea linkage between T101 and the In-111-labeled chelates and a higher complex stability and higher lipophilicity of In-111-1B4M and In-111-CHX-B appear to be responsible for lower liver and higher blood radioactivity for the 1B4M and CHX-B conjugates. C1 NCI,DEPT NUCL MED,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892. NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. RI Carrasquillo, Jorge/E-7120-2010; Jeong, Jae Min/E-2102-2012; OI Jeong, Jae Min/0000-0003-2611-6020; Carrasquillo, Jorge/0000-0002-8513-5734 NR 31 TC 19 Z9 19 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD NOV PY 1994 VL 35 IS 11 BP 1851 EP 1857 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PT868 UT WOS:A1994PT86800027 PM 7965168 ER PT J AU THOMPSON, FE BYERS, T AF THOMPSON, FE BYERS, T TI DIETARY ASSESSMENT RESOURCE MANUAL SO JOURNAL OF NUTRITION LA English DT Review ID FOOD FREQUENCY QUESTIONNAIRE; NHANES-II SURVEY; POSTMENOPAUSAL BREAST-CANCER; NUTRIENT DATA-BASE; HISTORY METHOD; MEASUREMENT ERROR; AMERICAN DIET; FAT INTAKE; NUTRITIONAL EPIDEMIOLOGY; CONFIDENCE-INTERVALS C1 CTR DIS CONTROL & PREVENT,NATL CTR CHRON DIS PREVENT & HLTH PROMOT,DIV NUTR,ATLANTA,GA 30341. RP THOMPSON, FE (reprint author), NCI,DIV CANC PREVENT & CONTROL,APPL RES BRANCH,EPN ROOM 313,6130 EXECUT BLVD MSC 7344,BETHESDA,MD 20892, USA. NR 233 TC 567 Z9 596 U1 10 U2 45 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 1994 VL 124 IS 11 SU S BP S2245 EP S2317 PG 73 WC Nutrition & Dietetics SC Nutrition & Dietetics GA PT280 UT WOS:A1994PT28000002 PM 7965210 ER PT J AU BALLARDBARBASH, R THOMPSON, FE GRAUBARD, BI KREBSSMITH, SM AF BALLARDBARBASH, R THOMPSON, FE GRAUBARD, BI KREBSSMITH, SM TI VARIABILITY IN PERCENT ENERGY FROM FAT THROUGHOUT THE DAY - IMPLICATIONS FOR APPLICATION OF TOTAL DIET GOALS SO JOURNAL OF NUTRITION EDUCATION LA English DT Article AB In spite of the general agreement that dietary recommendations apply to the diet over time, the quantitative levels for total and saturated fat have been used in establishing federal policy related to intakes for a single day, meal, and even an individual food. Application of these recommendations uniformly to meals across a day implies that fat intake is uniform throughout the day. This analysis of the 1985 Continuing Survey of Food Intakes by Individuals demonstrates that percent energy intake from fat across eating occasions within a day is not uniform. Percent energy intake from total and saturated fat is lower at the morning meal and at snacks among women at all levels of fat consumption, suggesting that fat is restricted more often at these two eating occasions. Intake of total and saturated fat was also more variable at these two eating occasions. These findings suggest that restricting fat intake at these eating occasions and liberalizing fat intake at midday and evening meals occurs commonly and may be an effective fat-reduction strategy. Daily variability in percent energy from fat should be considered in designing dietary fat reduction interventions and in applying quantitative recommendations for percent energy from total and saturated fat in nutrition guidance directed to individual meals. RP BALLARDBARBASH, R (reprint author), NCI,DIV CANC PREVENT & CONTROL,APPL RES BRANCH,EXECUT PLAZA N,BETHESDA,MD 20892, USA. NR 0 TC 6 Z9 6 U1 0 U2 1 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON ON L8N 3K7, CANADA SN 0022-3182 J9 J NUTR EDUC JI J. Nutr. Educ. PD NOV-DEC PY 1994 VL 26 IS 6 BP 278 EP 283 PG 6 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA PR313 UT WOS:A1994PR31300006 ER PT J AU LINET, MS MCLAUGHLIN, JK MALKER, HSR CHOW, WH WEINER, JA STONE, BJ ERICSSON, JLE FRAUMENI, JF AF LINET, MS MCLAUGHLIN, JK MALKER, HSR CHOW, WH WEINER, JA STONE, BJ ERICSSON, JLE FRAUMENI, JF TI OCCUPATION AND HEMATOPOIETIC AND LYMPHOPROLIFERATIVE MALIGNANCIES AMONG WOMEN - A LINKED REGISTRY STUDY SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID NON-HODGKINS-LYMPHOMA; RETROSPECTIVE COHORT MORTALITY; AGRICULTURAL RISK-FACTORS; SOFT-TISSUE SARCOMA; MULTIPLE-MYELOMA; CANCER MORTALITY; LEUKEMIA; WORKERS; DEATH; EXPOSURE AB Using a nationwide linked registry, we evaluated the incidence of several hematopoietic and lymphoproliferative (HLP) malignancies among Swedish women from 1961 to 1979 by industry and occupation. The risks of one or more types of HLP cancers (including the leukemias, non-Hodgkin's lymphoma, multiple myeloma, and mycosis fungoides) were significantly increased among women working in the agriculture and textile industries, housekeepers, and post office employees. Limitations of these linked-registry data include lack of detailed information on specific exposures and duration of employment, and the relatively small sizes of specific occupational cohorts. Nevertheless, as the proportion of women entering the workforce continues to increase, this data resource may provide additional clues to occupational determinants of HLP and other malignancies. C1 NATL BOARD OCCUPAT SAFETY & HLTH,S-17184 SOLNA,SWEDEN. NATL BOARD HLTH & WELF,STOCKHOLM,SWEDEN. RP LINET, MS (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 69 TC 26 Z9 27 U1 1 U2 1 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 NOV PY 1994 VL 36 IS 11 BP 1187 EP 1198 DI 10.1097/00043764-199411000-00004 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PV016 UT WOS:A1994PV01600004 PM 7861262 ER PT J AU BURNETT, CA DOSEMECI, M AF BURNETT, CA DOSEMECI, M TI USING OCCUPATIONAL MORTALITY DATA FOR SURVEILLANCE OF WORK-RELATED DISEASES OF WOMEN SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID DEATH CERTIFICATE; CANCER MORTALITY; ACCURACY; STATES; EXPOSURE; INDUSTRY; SMOKING; BREAST; MEN AB A recently developed source of occupational mortality data from 28 states for the years 1979 through 1990 can be used to meet goals for the surveillance of women's work-related diseases. A proportionate cancer mortality ratio analysis is used to illustrate use of the data to address the goals of identifying previously unrecognized work-related disease and targeting consultation or health promotion programs to appropriate occupations. Strengths of the data include broad geographical coverage and coverage of all causes of death and numerous industries and occupations. The data set is current and very large, with annual additions. The data have certain limitations. Death certificate information collected regarding occupation and cause of death may not be accurate; furthermore, death certificates have little information on potential confounding factors, such as smoking. C1 NCI,DIV CANC ETIOL,BETHESDA,MD 20892. RP BURNETT, CA (reprint author), NIOSH,DIV SURVEILLANCE HAZARD EVALUAT & FIELD STUDIES,4676 COLUMBIA PKWY,CINCINNATI,OH 45226, USA. NR 33 TC 20 Z9 20 U1 0 U2 0 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 NOV PY 1994 VL 36 IS 11 BP 1199 EP 1203 DI 10.1097/00043764-199411000-00005 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PV016 UT WOS:A1994PV01600005 PM 7861263 ER PT J AU DOSEMECI, M BLAIR, A AF DOSEMECI, M BLAIR, A TI OCCUPATIONAL-CANCER MORTALITY AMONG WOMEN EMPLOYED IN THE TELEPHONE INDUSTRY SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID DEATH CERTIFICATE OCCUPATION; ACCURACY; RATIO; COHORT; SURVEILLANCE; INFORMATION; INTERVIEW; EXPOSURE; SMOKING AB We conducted a mortality odds ratio (MOR) analysis among women employed in the telephone industry, using death certificates from 24 reporting states for 1984 through 1989. Usual occupation and industry from the death certificates were coded using the 1980 Bureau of the Census occupational and industrial classification system. There were 2444 cancer deaths among women in the telephone industry (code 441). Among younger (age <49) white women, significant excess risks were observed from cancers of the rectum (MOR = 3.3; 95% confidence interval [CI] = 1.2 to 8.7), connective tissue (MOR = 4.4; 95% CI = 2.2 to 8.8), breast (MOR = 1.6; 95% CI = 1.3 to 2.1), corpus uteri (MOR = 3.3; 95% CI = 1.5 to 7.5), ovary (MOR = 2.1; 95% CI = 1.3 to 3.5), and brain (MOR = 2.1; 95% CI = 1.2 to 3.7). Cancer of the connective tissue showed an almost sixfold risk (MOR = 5.5; 95% CI = 2.0 to 14.8) for the age group of 30 to 39 years. Excess risks of cancer of the connective tissue were observed among engineers and technicians, office workers, telephone operators, and mechanics and repairers (MOR = 8.5, 4.9, 1.7, and 4.4, respectively), suggesting a possible relationship with modern technological exposures in the telephone industry. Risks for cancers of the breast, corpus uteri, ovary, and brain were also elevated among these jobs. We did not have information on other risk factors for these cancer sites; therefore, socioeconomic status or lifestyle may explain these observed associations, particularly for the cancers of the reproductive system. Possible exposure to new instruments, machinery, or production procedures introduced in the modern telephone industry also may account for excess risks observed, particularly among younger women. RP DOSEMECI, M (reprint author), NCI,OCCUPAT STUDIES SECT,6130 EXECUT BLVD,MSC 7364,EPN,ROOM 418,BETHESDA,MD 20892, USA. NR 50 TC 25 Z9 25 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 NOV PY 1994 VL 36 IS 11 BP 1204 EP 1209 DI 10.1097/00043764-199411000-00006 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PV016 UT WOS:A1994PV01600006 PM 7861264 ER PT J AU FIGGS, LW DOSEMECI, M BLAIR, A AF FIGGS, LW DOSEMECI, M BLAIR, A TI RISK OF MULTIPLE-MYELOMA BY OCCUPATION AND INDUSTRY AMONG MEN AND WOMEN - A 24-STATE DEATH CERTIFICATE STUDY SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID PROPORTIONATE MORTALITY RATIO; NON-HODGKINS-LYMPHOMA; CANCER MORTALITY; MAGNETIC-FIELDS; WORKERS; LEUKEMIA; ACCURACY; HAZARDS; EPIDEMIOLOGY; DISCORDANCE AB This cancer surveillance investigation uses death certificates from 24 states for the period 1984-1989 to identify multiple myeloma and occupation associations and to stimulate hypotheses. A case-control study of multiple myeloma was created from 3,159,417 certificates in which 12,148 male and female cases were frequency matched by age, race, and gender with five controls per case. We screened 231 industries and 509 occupations. Women demonstrated significant excess risk among managers and administrators, post-secondary teachers, elementary teachers, social workers, other sales workers, waitresses, and hospital maids. Men showed significant risks among computer system scientists, veterinarians, elementary teachers, authors, engineering technicians, general office supervisors, insurance adjusters, barbers, electronic repairers, supervisors of extracting industries, production supervisors, photoengravers, and grader/dozer operators. Men and women elementary school teachers demonstrated the most consistent, statistically significant increased risk of multiple myeloma. RP FIGGS, LW (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,OCCUPAT STUDIES SECT,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 65 TC 24 Z9 24 U1 2 U2 3 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 NOV PY 1994 VL 36 IS 11 BP 1210 EP 1221 DI 10.1097/00043764-199411000-00007 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PV016 UT WOS:A1994PV01600007 PM 7861265 ER PT J AU WARD, MH DOSEMECI, M COCCO, P AF WARD, MH DOSEMECI, M COCCO, P TI MORTALITY FROM GASTRIC CARDIA AND LOWER ESOPHAGUS CANCER AND OCCUPATION SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID ADENOCARCINOMA; ACCURACY; STOMACH AB The incidence of adenocarcinoma of the gastric cardia and esophagus is increasing steadily in the United States. Little is known about the etiology of these cancers. We used occupation and industry information on the death certificates from 24 states (1984 to 1989) to conduct a case-control analysis of gastric cardia and gastric cardia/lower esophagus cancer. Risks were also calculated for other gastric cancers combined. Controls were deaths from other causes except cancer and gastrointestinal disorders. Increased risks of gastric cardia and cardia/lower esophagus among white women were found for administrative jobs (cardia odds ratio (OR) = 3.9; 95% confidence interval (CI), 1.5-9.8) and health professionals (cardia OR = 1.8; 95% CI, 0.6-5.3). Occupations associated with a lower socioeconomic status showed no significant excess risks. A similar pattern in risks was seen for men. RP WARD, MH (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,OCCUPAT STUDIES SECT,6130 EXECUT BLVD,MSC 7364,EPN,ROOM 418,BETHESDA,MD 20892, USA. NR 15 TC 10 Z9 10 U1 1 U2 1 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 NOV PY 1994 VL 36 IS 11 BP 1222 EP 1227 DI 10.1097/00043764-199411000-00008 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PV016 UT WOS:A1994PV01600008 PM 7861266 ER PT J AU ALAVANJA, MCR AKLAND, G BAIRD, D BLAIR, A BOND, A DOSEMECI, M KAMEL, F LEWIS, R LUBIN, J LYNCH, C MCMASTER, SB MOORE, M PENNYBACKER, M RITZ, L ROTHMAN, N ROWLAND, A SANDLER, DP SINHA, R SWANSON, C TARONE, R WEINBERG, C ZAHM, SH AF ALAVANJA, MCR AKLAND, G BAIRD, D BLAIR, A BOND, A DOSEMECI, M KAMEL, F LEWIS, R LUBIN, J LYNCH, C MCMASTER, SB MOORE, M PENNYBACKER, M RITZ, L ROTHMAN, N ROWLAND, A SANDLER, DP SINHA, R SWANSON, C TARONE, R WEINBERG, C ZAHM, SH TI CANCER AND NONCANCER RISK TO WOMEN IN AGRICULTURE AND PEST-CONTROL - THE AGRICULTURAL HEALTH STUDY SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID NON-HODGKINS-LYMPHOMA; BREAST-CANCER; HERBICIDES; MORTALITY; RESIDUES; FARMERS AB The Argicultural Health Study is a collaborative effort involving the National Cancer Institute, the US Environmental Protection Agency, and the National Institute of Environmental Health Sciences. A goal of this investigation is to establish a large cohort of men and women that can be followed prospectively for 10 years or more to evaluate the role of agricultural exposures in the development of cancer, neurologic disease, reproductive difficulties, childhood developmental problems, and other chronic diseases. The study also will provide an opportunity to assess the role that diet, cooking methods, and other lifestyle factors have on the cause of cancer and other diseases. The cohort will be composed of approximately 112,000 adult study subjects, including 42,000 women, making this one of the largest cohorts of women ever assembled for an epidemiologic investigation of environmental and occupational exposures. Children of farm families also will be enrolled. The study will be conducted in Iowa and North Carolina. Enrollment will begin in December 1993 and continue for 3 years. C1 US EPA,RES TRIANGLE PK,NC 27711. NIEHS,RES TRIANGLE PK,NC 27709. UNIV IOWA,IOWA CITY,IA 52242. SURVEY RES ASSOCIATES,RES TRIANGLE PK,NC. SRA TECHNOL INC,ARLINGTON,VA. RP ALAVANJA, MCR (reprint author), NATL CANC INST,6130 EXECUT BLVD,ROOM 543,ROCKVILLE,MD 20852, USA. RI Zahm, Shelia/B-5025-2015; Sinha, Rashmi/G-7446-2015; OI Sinha, Rashmi/0000-0002-2466-7462; Kamel, Freya/0000-0001-5052-6615; Baird, Donna/0000-0002-5544-2653 NR 17 TC 27 Z9 27 U1 0 U2 1 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 NOV PY 1994 VL 36 IS 11 BP 1247 EP 1250 DI 10.1097/00043764-199411000-00013 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PV016 UT WOS:A1994PV01600013 PM 7532217 ER PT J AU DIX, K DETERDING, LJ BURKA, LT TOMER, KB AF DIX, K DETERDING, LJ BURKA, LT TOMER, KB TI TRIS(2-CHLOROETHYL) PHOSPHATE PHARMACOKINETICS IN THE FISCHER-344 RAT - A COMPARISON OF CONVENTIONAL METHODS AND IN-VIVO MICRODIALYSIS COUPLED WITH TANDEM MASS-SPECTROMETRY SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID PROTEIN-BINDING; PROBES AB The pharmacokinetics of tris(2-chloroethyl) phosphate (TRCP, 20 mg/kg, iv) were investigated in awake male and female and anesthetized male Fischer 344 (F344) rats by conventional (CONV) sampling/detection methods (blood withdrawal with sample workup and analysis for TRCP). TRCP pharmacokinetics were also investigated in anesthetized male F344 rats using a new sampling/detection technique, in vivo microdialysis coupled with tandem mass spectrometry(1) (MD/MS/MS). The concentration of free TRCP in plasma versus time profiles were analyzed using noncompartmental methods to estimate pharmacokinetic parameters. Comparisons of mean parameter estimates were made for (1) awake males versus females in CONV studies (t test, no significant differences, p less than or equal to 0.05) and (2) awake and anesthetized males in CONV studies and anesthetized males in MD/MS/MS studies. There were significant differences (Scheffe's test) for the three groups of male rats, most notably the free TRCP concentration in plasma at early time points in CONV versus MD/MS/MS studies. The contributions of an indwelling jugular cannula, the blood sampling regimen, and the in vitro MD/MS/MS standard calibration curve were investigated. It appears that quantitation of TRCP by mass spectrometry using an in vitro standard calibration is responsible for the difference. C1 NIEHS,CHEM BRANCH,RES TRIANGLE PK,NC 27709. NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. RI Tomer, Kenneth/E-8018-2013 NR 21 TC 14 Z9 14 U1 0 U2 5 PU AMER PHARMACEUTICAL ASSN PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD NOV PY 1994 VL 83 IS 11 BP 1622 EP 1629 DI 10.1002/jps.2600831119 PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA PQ661 UT WOS:A1994PQ66100018 PM 7891285 ER PT J AU BUNGAY, PM DEDRICK, RL FENSTERMACHER, JD PATLAK, CS KRINDEL, P AF BUNGAY, PM DEDRICK, RL FENSTERMACHER, JD PATLAK, CS KRINDEL, P TI ESTIMATION OF BLOOD-SAMPLING ERRORS RESULTING FROM METABOLISM AND SOLUTE EXCHANGE BETWEEN PLASMA AND FORMED ELEMENTS SO JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS LA English DT Article DE SAMPLING; CONTINUOUS PLASMA, CONTINUOUS BLOOD, AND SERIAL BLOOD; AREA-UNDER-THE-CURVE DETERMINATION; ERROR IN; EXCHANGE BETWEEN PLASMA AND FORMED ELEMENTS; METABOLISM; PHARMACOKINETICS; SAMPLE STORAGE ARTIFACT ID PHARMACOKINETICS; DRUGS AB The origin and magnitude of potential errors in whole-blood sampling are predicted on the basis of a mathematical model. The model describes the kinetics of solute metabolism, breakdown, and interphase distribution (i.e., partitioning and exchange between formed elements and plasma) within a blood sample during sample withdrawal and storage. The model is applied to the determination of the integral over time of solute concentration in the plasma (area-under-the-curve, or AUC) from a sample withdrawn through an arterial or venous catheter. Errors in AUC determination can be substantial and are strongly dependent on the duration of sampling (T), the rate constants for solute degradation processes, the rate constant for solute exchange between the formed elements and the plasma (k(e)), and the equilibrium ratio for distribution of the solute between formed elements and plasma (R). When the value of the dimensionless group k(e)T/R is small, little solute exchanges between plasma water and formed elements before the two phases of the blood are separated. When k(e)T/R is large, the solute distribution is close to equilibrium at all times. In these two k(e)T/R limits, the contribution of solute redistribution to sampling error is small. Sizable errors resulting from redistribution are associated with intermediate values of k(e)T/R, even in the absence of metabolism and despite rapid separation of the phases at the end of the withdrawal period. Chemical conversion within either of the blood phases introduces additional sampling error under most circumstances. C1 HENRY FORD HOSP,DEPT ANESTHESIOL,DETROIT,MI 48202. SUNY STONY BROOK,DEPT SURG,STONY BROOK,NY 11794. RP BUNGAY, PM (reprint author), NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 13,ROOM 3N-17,BETHESDA,MD 20892, USA. NR 10 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1056-8719 J9 J PHARMACOL TOXICOL JI J. Pharmacol. Toxicol. Methods PD NOV PY 1994 VL 32 IS 3 BP 169 EP 175 DI 10.1016/1056-8719(94)90071-X PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA PT821 UT WOS:A1994PT82100007 PM 7858311 ER PT J AU BUNGAY, PM FENSTERMACHER, JD KRINDEL, P DEDRICK, RL PATLAK, CS AF BUNGAY, PM FENSTERMACHER, JD KRINDEL, P DEDRICK, RL PATLAK, CS TI CROSS-FLOW MEMBRANE PLASMAPHERESIS TECHNIQUE FOR CONTINUOUS EX-VIVO PLASMA SAMPLING SO JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS LA English DT Article DE PLASMAPHERESIS; CROSS-FLOW MEMBRANE; SAMPLING; CONTINUOUS PLASMA; CONTINUOUS BLOOD, AND SERIAL BLOOD; AREA-UNDER-THE-CURVE DETERMINATION; EXCHANGE BETWEEN PLASMA AND FORMED ELEMENTS; METABOLISM; PHARMACOKINETICS ID DRUG CONCENTRATION; MARKED DEPENDENCE; PHARMACOKINETICS; PHARMACODYNAMICS; THERAPEUTICS; TOXICOLOGY; RATIONALE; CURVE; SITE; AREA AB A technique is described for plasma sampling by continuous membrane plasmapheresis performed on blood flowing through an extracorporeal arteriovenous shunt. The plasmapheresis sampler in the shunt employs replaceable commercial planar membranes 2.5 cm in diameter. Validation tests were conducted for 0.6-mu m pore diameter microporous membranes with several low-molecular-weight, nonmetabolized solutes that either rapidly equilibrate between plasma and formed elements or remain extracellular. Ex vivo tests were performed for bolus intravenous administration to rabbits. The technique yielded values for time-averaged plasma concentrations comparable to those obtained with serial blood and continuous blood withdrawal methods. The new technique should be particularly advantageous when the distribution of the solute of interest between plasma and formed elements of the blood undergoes significant changes during the sampling interval as a result of binding, exchange, or metabolism in the formed element phase. C1 HENRY FORD HOSP,DEPT ANESTHESIOL,DETROIT,MI 48202. SUNY STONY BROOK,DEPT SURG,STONY BROOK,NY 11794. RP BUNGAY, PM (reprint author), NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 13,ROOM 3N-17,BETHESDA,MD 20892, USA. NR 15 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1056-8719 J9 J PHARMACOL TOXICOL JI J. Pharmacol. Toxicol. Methods PD NOV PY 1994 VL 32 IS 3 BP 177 EP 185 DI 10.1016/1056-8719(94)90072-8 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA PT821 UT WOS:A1994PT82100008 PM 7858312 ER PT J AU IRWIN, RP LIN, SZ ROGAWSKI, MA PURDY, RH PAUL, SM AF IRWIN, RP LIN, SZ ROGAWSKI, MA PURDY, RH PAUL, SM TI STEROID POTENTIATION AND INHIBITION OF N-METHYL-D-ASPARTATE RECEPTOR-MEDIATED INTRACELLULAR CA++ RESPONSES - STRUCTURE-ACTIVITY STUDIES SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID RAT HIPPOCAMPAL-NEURONS; PREGNENOLONE-SULFATE; HORMONE METABOLITES; GABA RECEPTOR; NEUROSTEROIDS; BRAIN; INCREASES; CHANNELS; POTENCY; MICE AB Pregnenolone sulfate and 15 related steroids were investigated for their effects on N-methyl-D-aspartate (NMDA)-induced elevations in intracellular Ca++ ([Ca++](i)) in cultured rat hippocampal neurons by microspectrofluorimetry with the Ca++-sensitive indicator fura-2. Several pregn-5-ene steroids markedly potentiated NMDA-mediated [Ca++](i) responses. Pregnenolone sulfate and its 21-acetoxy derivative and pregnenolone hemisuccinate were the most active. At a concentration of 50 mu M, each produced approximately 300% potentiation of 5 mu M NMDA responses. In addition, several steroids were identified that inhibited NMDA-induced elevations in [Ca++](i), the most potent of which was 3 alpha-hydroxy-5 beta-pregnan-20-one sulfate (IC50, 37 mu M). Concentration-response curves for NMDA in the presence of active steroids revealed noncompetitive interaction(s) of these steroids with the NMDA receptor. Although the mechanism(s) responsible for either steroid-induced augmentation or inhibition of NMDA-receptor responses is unknown, these data suggest the presence of one or more steroid recognition sites with a high degree of structural specificity associated with NMDA receptors. These results further raise the possibility that pregn-5-ene 3-sulfates and pregnane 3-sulfates could be endogenous modulators of NMDA receptor-mediated synaptic events. C1 NIMH,MOLEC PHARMACOL SECT,CLIN NEUROSCI BRANCH,BETHESDA,MD. NINCDS,NEURONAL EXCITABIL SECT,EPILEPSY RES BRANCH,BETHESDA,MD. VET AFFAIRS MED CTR,RES SERV,SAN DIEGO,CA. ELI LILLY & CO,LILLY RES LABS,INDIANAPOLIS,IN 46285. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 23 TC 140 Z9 146 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 1994 VL 271 IS 2 BP 677 EP 682 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PU300 UT WOS:A1994PU30000012 PM 7965782 ER PT J AU BALOW, JE AUSTIN, HA BOUMPAS, DT AF BALOW, JE AUSTIN, HA BOUMPAS, DT TI TREATMENT AND PROGNOSIS OF LUPUS NEPHRITIS SO JOURNAL OF RHEUMATOLOGY LA English DT Editorial Material ID INTRAVENOUS CYCLOPHOSPHAMIDE; CONTROLLED TRIAL; THERAPY; PREDNISONE RP BALOW, JE (reprint author), NIDDKD,KIDNEY DIS SECT,BLDG 10,ROOM 9N-222,BETHESDA,MD 20892, USA. NR 13 TC 6 Z9 6 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD NOV PY 1994 VL 21 IS 11 BP 1985 EP 1986 PG 2 WC Rheumatology SC Rheumatology GA PR235 UT WOS:A1994PR23500001 PM 7869297 ER PT J AU STAFFORD, FJ FLEISHER, TA LEE, G BROWN, M STRAND, V AUSTIN, HA BALOW, JE KLIPPEL, JH AF STAFFORD, FJ FLEISHER, TA LEE, G BROWN, M STRAND, V AUSTIN, HA BALOW, JE KLIPPEL, JH TI A PILOT-STUDY OF ANTI-CDS RICIN-A CHAIN IMMUNOCONJUGATE IN SYSTEMIC LUPUS-ERYTHEMATOSUS SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE SYSTEMIC LUPUS ERYTHEMATOSUS; MONOCLONAL ANTIBODY; IMMUNOTHERAPY; IMMUNOTOXIN ID A-CHAIN; MONOCLONAL-ANTIBODY; MURINE LUPUS; PLUS AB Objective. To determine the safety and clinical and biological effects of a murine monoclonal anti-CD5 ricin A chain immunoconjugate (CD5 Plus) in patients with systemic lupus erythematosus (SLE). Methods. An open label phase I study of CD5 Plus. A dose of 0.1 mg/kg was administered intravenously on 5 consecutive days. A second course of immunoconjugate was given to patients who failed to show any clinical response one to 2 months later. Results. Six patients (4 with glomerulonephritis and 2 with thrombocytopenia) were studied. Improvement was documented in 2 patients with nephritis; no effect on thrombocytopenia was observed. Adverse effects were mild and transient. Relative to pretreatment lymphocyte counts, the mean reduction in CD3+ T cell count was 69% at 2 weeks, 32% at one month, and 34% at 6 months following initial treatment. A comparable decrease in all subpopulations of mature T cells was noted, using a variety of surface markers, including CD4 and CD8. The mean percentage of T cells expressing the activation markers HLA-DR and interleukin 2R (IL-2R) was high before treatment, and remained so. There was a transient decrease in CD5+ B cells, but no persistent depletion of total B cell numbers. There was no consistent change in natural killer cell populations. Conclusion. Anti-CDS ricin A chain immunoconjugate is well tolerated in patients with SLE, causes modest T cell depletion which may persist for months, and may have some clinical efficacy in lupus nephritis. C1 NIDDKD,KIDNEY DIS SECT,BETHESDA,MD 20892. NIH,CTR CLIN,BETHESDA,MD 20892. RP STAFFORD, FJ (reprint author), NIAMS,ARTHRITIS & RHEUMATISM BRANCH,BLDG 10,ROOM 9S 205,BETHESDA,MD 20892, USA. NR 9 TC 23 Z9 23 U1 0 U2 2 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD NOV PY 1994 VL 21 IS 11 BP 2068 EP 2070 PG 3 WC Rheumatology SC Rheumatology GA PR235 UT WOS:A1994PR23500017 PM 7532717 ER PT J AU BRAY, VJ WEST, SG SCHULTZ, KT BOUMPAS, DT RUBIN, RL AF BRAY, VJ WEST, SG SCHULTZ, KT BOUMPAS, DT RUBIN, RL TI ANTIHISTONE ANTIBODY PROFILE IN SULFASALAZINE INDUCED LUPUS SO JOURNAL OF RHEUMATOLOGY LA English DT Note DE DRUG INDUCED LUPUS; ANTIHISTONE ANTIBODIES; SULFASALAZINE; OLSALAZINE ID AUTOANTIBODIES; CHROMATIN AB Two patients developed drug induced lupus secondary to sulfasalazine (SSZ). One patient was receiving SSZ for Crohn's disease and was subsequently treated with olsalazine, which lacks the sulfapyridine component of SSZ. Her inflammatory bowel disease (IBD) remained controlled and she did not develop a recurrence of lupus, suggesting that olsalazine is safe in patients with IBD and a history of SSZ induced lupus. The SSZ induced antibodies were predominantly IgG against the (H2A-H2B)-DNA complex. Since lupus induced by 7 other drugs was associated with a similar antibody response, our findings support the existence of a common pathway for autoantibody induction. C1 MED GRP 28, DEPT MED, ELLSWORTH AFB, SD USA. NIH, BETHESDA, MD 20892 USA. SCRIPPS RES INST, LA JOLLA, CA USA. RP BRAY, VJ (reprint author), FITZSIMONS ARMY MED CTR, DEPT MED, RHEUMATOL SERV, HSHG MDR, AURORA, CO 80045 USA. NR 9 TC 20 Z9 20 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD NOV PY 1994 VL 21 IS 11 BP 2157 EP 2158 PG 2 WC Rheumatology SC Rheumatology GA PR235 UT WOS:A1994PR23500033 PM 7869327 ER PT J AU WU, MC AF WU, MC TI DESIGN ASPECTS FOR CLINICAL-TRIALS WITH REPEATED-MEASURES IN THE PRESENCE OF INFORMATIVE CENSORING SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE INFORMATIVE CENSORING; LONGITUDINAL APPROACH; MARGINAL APPROACH ID MODELS; TESTS AB Likelihood-based procedures derived under the linear random effects model and distribution-free tests obtained by combining marginal U statistics as well as by ranking the individual effects are reviewed for clinical trials with repeated measures. Simulation studies are illustrated to evaluate the effects of informative censoring and model misspecifications on statistical power and sample size. The results indicate that in some situations with information censoring the combined marginal U statistic could suffer severe loss of power. Furthermore, in the presence of informative censoring with some model misspecifications all other procedures could also suffer some power losses, although not as severe. Therefore, in planning clinical trials in which informative censoring is likely to occur, it is important to conduct some simulation studies based on realistic parameter estimates such that a proper method of analysis could be selected and appropriate sample size adjustments could be made. RP WU, MC (reprint author), NHLBI,BIOSTAT RES BRANCH,BETHESDA,MD 20892, USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD NOV PY 1994 VL 42 IS 1-2 BP 109 EP 122 DI 10.1016/0378-3758(94)90192-9 PG 14 WC Statistics & Probability SC Mathematics GA PQ720 UT WOS:A1994PQ72000008 ER PT J AU ELLENBERG, SS DIXON, DO AF ELLENBERG, SS DIXON, DO TI STATISTICAL ISSUES IN DESIGNING CLINICAL-TRIALS OF AIDS TREATMENTS AND VACCINES SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE SIMULTANEOUS STUDY ENROLLMENT; FACTORIAL DESIGN; DRUG INTERACTIONS; SELECTION BIAS; LARGE SIMPLE TRIAL; SURROGATE END-POINT; EQUIVALENCE TRIAL; NONPROPORTIONAL HAZARDS ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; UNITED-STATES PHYSICIANS; FACTORIAL-DESIGNS; SURROGATE MARKERS; HIV-INFECTION; ZIDOVUDINE; PREVENTION; EFFICIENCY; SAFETY; COST AB The acquired immunodeficiency syndrome (AIDS) was identified somewhat more than a decade ago; in this brief interval, medical and statistical researchers have faced many new problems (and some old ones that now seem worse) as they have attempted to develop effective and efficient research programs. In addition to the scientific issues that must be confronted in studying a new disease, researchers have had to incorporate in their design considerations the concerns of a highly involved patient and at-risk community. Some of the research approaches being suggested have important implications for statistical aspects of design, analysis and interpretation. In the therapeutic area, policies encouraging the participation of individuals in multiple trials that may overlap chronologically solves certain types of problems but generates others. The use of large, simple trials to obtain useful information on infrequently occurring but important adverse events is unorthodox during the relatively early stages of drug development, but may be an attractive mechanism for providing wider access to drug in 'parallel track' programs. The planning of large efficacy trials for the first generation of AIDS vaccine candidates has also uncovered a variety of problematic issues that will require the attention of statiticians. C1 NIAID,DIV AIDS,BETHESDA,MD 20892. NR 35 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD NOV PY 1994 VL 42 IS 1-2 BP 123 EP 135 DI 10.1016/0378-3758(94)90193-7 PG 13 WC Statistics & Probability SC Mathematics GA PQ720 UT WOS:A1994PQ72000009 ER PT J AU SIMON, R AF SIMON, R TI PROBLEMS OF MULTIPLICITY IN CLINICAL-TRIALS SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE CLINICAL TRIALS; MULTIPLE COMPARISONS; MULTIVARIATE; SEQUENTIAL ANALYSIS; METAANALYSIS; BAYESIAN METHODS ID QUALITATIVE INTERACTIONS; ACCUMULATING DATA; PLACEBO CONTROLS; PATIENT SUBSETS; COMPETING RISK; TESTS; ENDPOINTS AB Most of the uncertainties in the conclusions of randomized clinical trials result either from inadequate sample size or from problems of multiplicity. Problems of multiplicity result from the testing of multiple hypotheses or the testing of a hypothesis at multiple points in time or in multiple ways. I review several common problems of this type: multiple analyses of accumulating data, analyses of multiple endpoints, multiple subsets of patients, multiple treatment group contrasts and interpreting the results of multiple clinical trials. Multiplicity issues are of importance both within the frequentist and Bayesian frameworks of inference. Within the Neyman-Pearson theory hypotheses must be pre-specified. With Bayesian methods the prior distributions must be pre-specified. I review some recently developed methods for dealing with difficult problems of multiplicity in the above mentioned categories. Multiplicity problems sometimes reflect inadequately specified objectives of the clinical trial and proper solutions involve clarification at the design stage of hypotheses to be tested and analysis strategies to be used. C1 NCI,BIOMETR RES BRANCH,BETHESDA,MD 20892. NR 52 TC 7 Z9 7 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD NOV PY 1994 VL 42 IS 1-2 BP 209 EP 221 DI 10.1016/0378-3758(94)90197-X PG 13 WC Statistics & Probability SC Mathematics GA PQ720 UT WOS:A1994PQ72000013 ER PT J AU SZAPARY, D BARBER, T DWYER, NK BLANCHETTEMACKIE, EJ SIMONS, SS AF SZAPARY, D BARBER, T DWYER, NK BLANCHETTEMACKIE, EJ SIMONS, SS TI MICROTUBULES ARE NOT REQUIRED FOR GLUCOCORTICOID RECEPTOR-MEDIATED GENE INDUCTION SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article ID HUMAN GINGIVAL FIBROBLASTS; NUCLEAR-LOCALIZATION; HEAT-SHOCK; CYTOPLASMIC MICROTUBULES; PROGESTERONE-RECEPTOR; PROTEIN; BINDING; TRANSLOCATION; MECHANISM; TUBULIN AB Steroid-free glucocorticoid receptors are generally considered to reside in the cytoplasm of cells. After the binding of steroids, the receptors translocate into the nucleus in a manner that has been proposed to involve microtubules. However, some results with inhibitors of microtubule assembly argue to the contrary. In all of these studies, only the whole cell localization of receptors has been examined; the biological activity of these receptors has not been determined. We now report that steroid-induced gene expression is maintained in the absence of intact microtubules. This argues that microtubules are not required for either the nuclear translocation or biological activity of glucocorticoid receptors. C1 NIDDK,CELLULAR & MOLEC BIOL LAB,STEROID HORMONES SECT,BETHESDA,MD 20892. NIDDK,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. NR 32 TC 17 Z9 19 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD NOV PY 1994 VL 51 IS 3-4 BP 143 EP 148 DI 10.1016/0960-0760(94)90087-6 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA PW164 UT WOS:A1994PW16400004 PM 7981123 ER PT J AU LESHNER, AI AF LESHNER, AI TI A COMPREHENSIVE STRATEGY FOR IMPROVING DRUG-ABUSE TREATMENT SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Editorial Material RP LESHNER, AI (reprint author), NIDA,5600 FISHERS LANE,ROOM 10-05,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD NOV-DEC PY 1994 VL 11 IS 6 BP 583 EP 586 DI 10.1016/0740-5472(94)90010-8 PG 4 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA PZ700 UT WOS:A1994PZ70000010 PM 7884842 ER PT J AU SHAPIRO, BA NAVETTA, J AF SHAPIRO, BA NAVETTA, J TI A MASSIVELY-PARALLEL GENETIC ALGORITHM FOR RNA SECONDARY STRUCTURE PREDICTION SO JOURNAL OF SUPERCOMPUTING LA English DT Article DE GENETIC ALGORITHMS; RNA STRUCTURE PREDICTION; MASSIVELY PARALLEL; DYNAMIC PROGRAMMING; OPTIMIZATION AB We present a new method for predicting RNA secondary structure based on a genetic algorithm. The algorithm is designed to run on a massively parallel SIMD computer. Statistical analysis shows that the program performs well when compared to a dynamic programming algorithm used to solve the same problem. The program has also pointed out a long-standing simplification in the implementation of the original dynamic programming algorithm that sometimes causes it not to find the optimal secondary structure. RP SHAPIRO, BA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC BIOL DIAG & CTR,MATH BIOL LAB,IMAGE PROC SECT,FREDERICK,MD 21702, USA. NR 16 TC 53 Z9 58 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0920-8542 J9 J SUPERCOMPUT JI J. Supercomput. PD NOV PY 1994 VL 8 IS 3 BP 195 EP 207 DI 10.1007/BF01204728 PG 13 WC Computer Science, Hardware & Architecture; Computer Science, Theory & Methods; Engineering, Electrical & Electronic SC Computer Science; Engineering GA QA350 UT WOS:A1994QA35000001 ER PT J AU CALDWELL, JB YANCEY, KB ENGLER, RJM JAMES, WD AF CALDWELL, JB YANCEY, KB ENGLER, RJM JAMES, WD TI EPIDERMOLYSIS-BULLOSA ACQUISITA - EFFICACY OF HIGH-DOSE INTRAVENOUS IMMUNOGLOBULINS SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter ID GLOBULIN C1 NATL INST HLTH,DERMATOL BRANCH,BETHESDA,MD. WALTER REED ARMY MED CTR,DEPT ALLERGY & IMMUNOL,WASHINGTON,DC. RP CALDWELL, JB (reprint author), WALTER REED ARMY MED CTR,DEPT DERMATOL,WASHINGTON,DC 20307, USA. NR 3 TC 34 Z9 34 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 NOV PY 1994 VL 31 IS 5 BP 827 EP 828 PN 1 PG 2 WC Dermatology SC Dermatology GA PN838 UT WOS:A1994PN83800035 PM 7929940 ER PT J AU PANZA, JA LAURIENZO, JM CURIEL, RV QUYYUMI, AA CANNON, RO AF PANZA, JA LAURIENZO, JM CURIEL, RV QUYYUMI, AA CANNON, RO TI TRANSESOPHAGEAL DOBUTAMINE STRESS ECHOCARDIOGRAPHY FOR EVALUATION OF PATIENTS WITH CORONARY-ARTERY DISEASE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; LOW-DOSE DOBUTAMINE; ANATOMIC CORRELATIONS; CLINICAL-APPLICATIONS; IMAGE ORIENTATION; 2-DIMENSIONAL ECHOCARDIOGRAPHY; DIPYRIDAMOLE ECHOCARDIOGRAPHY; THROMBOLYTIC THERAPY; CARDIAC RISK; INFUSION AB Objectives. The present study was undertaken to determine the safety, feasibility and diagnostic accuracy of transesophageal dobutamine stress echocardiography for the evaluation of patients with known or suspected coronary artery disease. Background. Dobutamine stress echocardiography has proved to be a valuable method for detecting and prognosticating ischemic heart disease. In addition, it may provide accurate information about myocardial viability in patients with systolic dysfunction. However, in some patients the technique may be limited by poor myocardial imaging with the conventional transthoracic approach. Methods. Seventy-six patients (62 men, 14 women; mean age +/- SD 60 +/- 10 years) who underwent coronary angiography were included in the study. Transesophageal stress echocardiograms were performed after withdrawal of antianginal medications for 48 h. Dobutamine was infused at a starting dose of 2.5 mu g/kg body weight per min and was increased by 5-mu g/kg per min increments every 5 min to a maximum of 40 mu g/kg per min. Two-dimensional views were acquired at each stage and digitized for subsequent analysis. The left ventricle was divided into 16 segments, and each segment was assigned to a major coronary artery with the use of a model of regional distribution of coronary perfusion. Results. Sixty two of the 76 patients had angiographic evidence of coronary artery disease. New or worsening regional wall motion abnormalities developed during dobutamine infusion in 55 of these 62 patients and in none of the 14 patients with normal coronary arteries (sensitivity 89%, specificity 100%, overall accuracy 91%). Regional wall motion abnormalities in the distribution of more than one major coronary artery were seen in 3 of the 25 patients with single-vessel coronary artery disease and in 30 of the 37 patients with multivessel disease (p < 0.0001). The test was successfully completed in 73 (96%) of the 76 patients; it was discontinued in the remaining 3 patients because of intolerance to the probe. No major complications occurred in any patient. Minor complications developed in seven patients but did not affect the diagnostic accuracy of the test. Conclusions. Transesophageal dobutamine stress echocardiography is a safe, feasible and accurate method for assessing coronary artery disease. Its use should be considered in patients who have a suboptimal ultrasound window, and it provides an excellent tool for clinical investigations based on ultrasound imaging of the myocardium. RP PANZA, JA (reprint author), NHLBI,ECHOCARDIOG LAB,CARDIOL BRANCH,BLDG 10,ROOM 7B-15,BETHESDA,MD 20892, USA. NR 36 TC 57 Z9 58 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 1 PY 1994 VL 24 IS 5 BP 1260 EP 1267 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PN650 UT WOS:A1994PN65000012 PM 7930248 ER PT J AU SUTHERLAND, CM CHMIEL, JS HENSON, DE WINCHESTER, DP AF SUTHERLAND, CM CHMIEL, JS HENSON, DE WINCHESTER, DP TI PATIENT CHARACTERISTICS, METHODS OF DIAGNOSIS, AND TREATMENT OF MUCOUS-MEMBRANE MELANOMA IN THE UNITED-STATES-OF-AMERICA SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID MUCOSAL MELANOMAS AB BACKGROUND: There is limited information regarding mucous membrane malignant melanoma. STUDY DESIGN: The American College of Surgeons performed a patient care and evaluation study of malignant melanoma for 1981 and 1987 to determine the presenting symptoms, methods of evaluation, clinical management, and disease outcome. Previous reports on malignant melanoma of the skin and ocular melanoma have been prepared. This report details the findings for 60 patients with mucous membrane melanoma diagnosed in 1981 and 97 patients diagnosed in 1987. RESULTS: The patients with mucous membrane melanoma were generally older than patients with either skin or ocular melanoma. Significantly more females than males were reported, with no significant change between study years. Proportionally, more blacks: were diagnosed with this condition than in the previous studies of skin and ocular melanoma. The patients with melanoma in this study had a poor prognosis based on characteristics known to be important for skin melanoma. As for patients with skin melanoma, most patients with mucous membrane melanoma were treated with operation alone, but good results were infrequent in patients with mucous membrane melanoma. Local, regional, and systemic recurrences were significant problems and overall survival was poor. CONCLUSIONS: We need new methods of treating these patients to control the disease and improve survival rates. C1 NORTHWESTERN UNIV,SCH MED,DEPT PREVENT MED,CHICAGO,IL. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. AMER COLL SURG,CHICAGO,IL. RP SUTHERLAND, CM (reprint author), TULANE UNIV,SCH MED,DEPT SURG,1430 TULANE AVE,NEW ORLEANS,LA 70112, USA. NR 9 TC 23 Z9 23 U1 0 U2 0 PU AMER COLL SURGEONS PI CHICAGO PA 54 EAST ERIE ST, CHICAGO, IL 60611 SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD NOV PY 1994 VL 179 IS 5 BP 561 EP 566 PG 6 WC Surgery SC Surgery GA PQ169 UT WOS:A1994PQ16900009 PM 7952459 ER PT J AU MECKLENBURG, R AF MECKLENBURG, R TI ORAL-CANCER SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Letter RP MECKLENBURG, R (reprint author), NCI,SMOKING & TOBACCO CONTROL PROG EPN 241,POTOMAC,MD, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD NOV PY 1994 VL 125 IS 11 BP 1421 EP 1424 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA PQ507 UT WOS:A1994PQ50700003 PM 7832881 ER PT J AU BROWN, LJ DEPAOLA, DP DUGONI, AA NIESSEN, LC PRIDE, JR AF BROWN, LJ DEPAOLA, DP DUGONI, AA NIESSEN, LC PRIDE, JR TI SPOTLIGHT ON TODAYS MAJOR ISSUES SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Discussion C1 BAYLOR COLL DENT,DALLAS,TX 75246. UNIV SAN FRANCISCO,PACIFIC SCH DENT,SAN FRANCISCO,CA 94117. RP BROWN, LJ (reprint author), NIDR,ORAL DIS PREVENT PROGRAM,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD NOV PY 1994 VL 125 IS 11 BP 1459 EP 1465 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA PQ507 UT WOS:A1994PQ50700012 PM 7963097 ER PT J AU BRESLOW, RA BERGSTROM, N AF BRESLOW, RA BERGSTROM, N TI NUTRITIONAL PREDICTION OF PRESSURE ULCERS SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID ELDERLY PATIENTS; SORE RISK; FRACTURE AB This article focuses on nutritional risk factors that predict the development of pressure ulcers in hospital and nursing home patients. Cross-sectional studies associate inadequate energy and protein intake; underweight; low triceps skinfold measurement; and low serum albumin, low serum cholesterol, and low hemoglobin levels with pressure ulcers. Prospective studies identify inadequate energy and protein intake, a poor score on the Braden scale (a risk assessment instrument that includes a nutrition component), and possibly low serum albumin level as risk factors for developing a pressure ulcer. Nutritionists should provide a high-energy, high-protein diet for patients at risk of development of pressure ulcers to improve their dietary intake and nutritional status. C1 UNIV NEBRASKA,MED CTR,COLL NURSING,DEPT NURSING EDUC ADM & SCI,OMAHA,NE. RP BRESLOW, RA (reprint author), NCI,CANC PREVENT FELLOWSHIP OFF,EXECUT PLAZA S,SUITE T41,ROCKVILLE,MD 20892, USA. NR 33 TC 25 Z9 26 U1 0 U2 2 PU AMER DIETETIC ASSN 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 NOV PY 1994 VL 94 IS 11 BP 1301 EP 1304 DI 10.1016/0002-8223(94)92464-3 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA PQ974 UT WOS:A1994PQ97400019 PM 7963176 ER PT J AU HODES, RJ AF HODES, RJ TI FRAILTY AND DISABILITY - CAN GROWTH-HORMONE OR OTHER TROPHIC AGENTS MAKE A DIFFERENCE SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Note RP HODES, RJ (reprint author), NIA, OFF DIRECTOR, BLDG 31, RM 5C35, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 11 TC 11 Z9 11 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 1994 VL 42 IS 11 BP 1208 EP 1211 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA PQ005 UT WOS:A1994PQ00500013 PM 7963210 ER PT J AU HUMPHREYS, BL AF HUMPHREYS, BL TI TOWARD DATA STANDARDS FOR CLINICAL NURSING INFORMATION - COMMENT SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Letter RP HUMPHREYS, BL (reprint author), NATL LIB MED,BETHESDA,MD, USA. NR 3 TC 3 Z9 3 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD NOV-DEC PY 1994 VL 1 IS 6 BP 472 EP 474 PG 3 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA QE642 UT WOS:A1994QE64200009 ER PT J AU WAALKES, MP REHM, S AF WAALKES, MP REHM, S TI CADMIUM AND PROSTATE-CANCER SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Review ID WISTAR CRL-(WI)BR RATS; DOSE-RESPONSE ANALYSIS; TESTOSTERONE PROPIONATE; SEPARATED EPITHELIUM; CYPROTERONE-ACETATE; PRODUCTION WORKERS; SPECIAL EMPHASIS; EXPOSED WORKERS; TUMOR-INDUCTION; INJECTION SITE AB Prostatic cancer is a common and frequently lethal malignant disease. In the United States and other countries the incidence and mortality rate of prostate cancer continue to rise. Cancer of the prostate has an extremely complex etiology and appears dependent on a variety of factors, making linkage to a single factor very difficult to detect. Cadmium is a metallic toxin of great environmental and occupational concern. Cadmium exposure has been associated with human prostatic cancer in some, but not all, epidemiologic studies. Some studies indicate that tissue levels of cadmium in the human prostate correlate with malignant disease. Any association between cadmium and prostatic cancer has been controversial, in large part because of a previous lack of relevant animal models. However, several chronic studies in rats revealing a correlation between cadmium exposure and prostatic tumors have been published over the last several years. These include a study of oral cadmium exposure, a route extremely relevant to human exposure. Several of these chronic studies indicate a hormonal dependence of cadmium-induced prostate cancer. Other supportive work continues to accumulate, such as studies showing in vitro malignant transformation of prostatic epithelial cells with cadmium exposure. In addition, there are indications that the primary biologic tolerance system for cadmium (i.e., the metallothionein gene) may be only poorly active in the specific lobes oi the rat prostate in which cadmium induces tumors. The induction in rats of prostate cancer by cadmium treatment clearly supports, but does not definitively establish, a possible role for cadmium as an etiological agent in human prostate cancer. Further research, however, will be required to establish the precise role of cadmium in this important human malignancy. RP WAALKES, MP (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC ETIOL,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. NR 106 TC 85 Z9 90 U1 3 U2 7 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 NOV PY 1994 VL 43 IS 3 BP 251 EP 269 PG 19 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA PR013 UT WOS:A1994PR01300001 PM 7966437 ER PT J AU SIMMONS, JE YANG, RSH SVENDSGAARD, DJ THOMPSON, MB SEELY, JC MCDONALD, A AF SIMMONS, JE YANG, RSH SVENDSGAARD, DJ THOMPSON, MB SEELY, JC MCDONALD, A TI TOXICOLOGY STUDIES OF A CHEMICAL-MIXTURE OF 25 GROUNDWATER CONTAMINANTS - HEPATIC AND RENAL ASSESSMENT, RESPONSE TO CARBON-TETRACHLORIDE CHALLENGE, AND INFLUENCE OF TREATMENT-INDUCED WATER RESTRICTION SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Article ID CHLOROFORM-INDUCED HEPATOTOXICITY; COMPLEX WASTE MIXTURES; LIVER-INJURY; B6C3F1 MICE; RAT-LIVER; POTENTIATION; TOXICITY; TRICHLOROETHYLENE; LETHALITY; ACETONE AB Because groundwater contamination is an important environmental concern, we examined the hepatic and renal effects of repeated exposure to a mixture of 25 chemicals frequently found in groundwater near hazardous-waste disposal sites and the effect of such exposure on carbon tetrachloride (CCl4) toxicity. Adult male F-344 rats received ad libitum deionized water and feed (Ad Lib Water) or ad libitum 10% MIX (referring to 10% of a technically achievable stock mixture) and feed for 14 d. Because exposure to the 25-chemical mixture via the drinking water resulted in decreased water and feed consumption, restricted deionized water and feed controls (Restricted Water) were included. On d 14, rats were gavaged with 0, 0.0375, 0.05, 0.075 or 0.15 ml CCl4/kg, and hepatic and renal toxicity assessed 24 h later. Little or no hepatic and renal toxicity was observed in rats exposed to 10% MIX alone. No hepatic or renal lesions occurred that could be attributed to 10% MIX alone. Slight but statistically significant alterations, of uncertain biological significance, resulted from the water treatments: 10% MIX increased alanine aminotransferase, urea nitrogen (BUN), and BUN/creatinine ratio; Restricted Water increased 5'-nucleotidase and decreased alkaline phosphatase. Relative kidney weight was increased by both 10% MIX and Restricted Water. CCl4 resulted in significant dosage-dependent hepatotoxicity in all three water treatment groups but had little or no effect on renal indicators of toxicity. Relative to Ad Lib Water, significantly greater hepatotoxicity occurred in both 10% MIX and Restricted Water rats. The response to CCl4 in the Restricted Water rats was similar to that of 10% MIX rats, indicating that a substantial portion of the effect of 10% MIX on CCl4 hepatotoxicity is due to decreased water and feed intake. C1 COLORADO STATE UNIV,DEPT ENVIRONM HLTH,FT COLLINS,CO 80523. NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. PATHCO INC,RES TRIANGLE PK,NC. RP SIMMONS, JE (reprint author), US EPA,HLTH EFFECTS RES LAB,MD-74,RES TRIANGLE PK,NC 27711, USA. NR 61 TC 21 Z9 21 U1 2 U2 5 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 NOV PY 1994 VL 43 IS 3 BP 305 EP 325 PG 21 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA PR013 UT WOS:A1994PR01300004 PM 7966440 ER PT J AU WALTHER, MM TRAHAN, EE COOPER, M VENZON, D LINEHAN, WM AF WALTHER, MM TRAHAN, EE COOPER, M VENZON, D LINEHAN, WM TI SURAMIN INHIBITS PROLIFERATION AND DNA-SYNTHESIS IN TRANSITIONAL CARCINOMA CELL-LINES SO JOURNAL OF UROLOGY LA English DT Article DE CARCINOMA, TRANSITIONAL CELL; SURAMIN; DNA ID GROWTH-FACTOR RECEPTOR; HUMAN PROSTATE CARCINOMA; URINARY-BLADDER; CYTOTOXICITY INVITRO; CANCER; BINDING; DRUG; EXPRESSION AB Suramin is polysulfonated napthylurea which has a broad range of antitumor activity. The mechanism of action of suramin is not completely understood, although it is known to inhibit enzymes in all cellular compartments, inhibit steroidogenesis and interfere with ligand-receptor binding. Suramin's large molecular size and negative charge should make it poorly absorbed through the bladder mucosa, a desired characteristic for an intravesical chemotherapeutic agent. We examined the ability of suramin to inhibit thymidine uptake and decrease cellular proliferation in 4 transitional cell carcinoma cell lines grown in vitro to determine if suramin might be a new candidate drug of treatment for patients with superficial bladder cancer. Suramin inhibited cellular proliferation of all cell lines tested (MBT2, T24, RT4 and TCCSUP) in a dose-dependent fashion. Fifty per cent inhibition of cellular proliferation compared with controls was seen with suramin concentrations of 250 to 400 mu g./ml. by, at most, 5 to 9 days of exposure. The cell Line RT4 was the cell Line most sensitive to the growth inhibitory effect of suramin, with 50% growth inhibition compared with controls achieved after 3 days' exposure to a suramin concentration of 100 mu g./ml. Suramin inhibited DNA synthesis in a dose-dependent fashion, as measured by thymidine uptake, in 3 of the 4 cell lines tested (MBT2, T24, and RT4). Suramin inhibited thymidine uptake by TCCSUP in a dose-dependent fashion, but did not achieve statistical significance. C1 NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. RP WALTHER, MM (reprint author), NCI,BIOSTAT & DATA MANAGEMENT SECT,SURG BRANCH,UROL ONCOL SECT,BLDG 10,ROOM 2B43,BETHESDA,MD 20892, USA. RI Venzon, David/B-3078-2008 NR 28 TC 9 Z9 9 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 1994 VL 152 IS 5 BP 1599 EP 1602 PN 1 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA PL685 UT WOS:A1994PL68500079 PM 7933214 ER PT J AU CHODAK, GW SCARDINO, PT MILLER, GJ BRENDLER, CB OESTERLING, JW WHITMORE, WF CATALONA, WJ ANDRIOLE, GL FEIGHTNER, JW PEARSON, JD AF CHODAK, GW SCARDINO, PT MILLER, GJ BRENDLER, CB OESTERLING, JW WHITMORE, WF CATALONA, WJ ANDRIOLE, GL FEIGHTNER, JW PEARSON, JD TI DISCUSSION SO JOURNAL OF UROLOGY LA English DT Discussion C1 UNIV CHICAGO,PRITZKER SCH MED,CHICAGO,IL 60637. UNIV COLORADO,HLTH SCI CTR,DEPT PHYSIOL,DENVER,CO 80262. JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT UROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV HOSP,JAMES BUCHANAN BRADY UROL INST,BALTIMORE,MD 21205. MAYO CLIN & MAYO FDN,DEPT UROL,ROCHESTER,MN 55905. MAYO CLIN & MAYO FDN,BIOSTAT SECT,ROCHESTER,MN 55905. MEM SLOAN KETTERING CANC CTR,DEPT SURG,UROL SERV,NEW YORK,NY 10021. WASHINGTON UNIV,SCH MED,DIV UROL SURG,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DIV LAB MED,ST LOUIS,MO 63110. MCMASTER UNIV,DEPT FAMILY MED,HAMILTON L8S 4L8,ON,CANADA. NIA,GERONTOL RES CTR,LONGITUDINAL STUDIES BRANCH,BALTIMORE,MD. RP CHODAK, GW (reprint author), WEISS MEM HOSP,CTR PROSTATE & UROL,4646 N MARINE DR,CHICAGO,IL 60604, 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 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 1994 VL 152 IS 5 BP 1730 EP 1731 PN 2 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA PL686 UT WOS:A1994PL68600015 ER PT J AU PEARSON, JD CARTER, HB AF PEARSON, JD CARTER, HB TI NATURAL-HISTORY OF CHANGES IN PROSTATE-SPECIFIC ANTIGEN IN EARLY-STAGE PROSTATE-CANCER SO JOURNAL OF UROLOGY LA English DT Article; Proceedings Paper CT Conference on Detection and Treatment of Early Stage Prostate Cancer CY DEC 03-05, 1993 CL CRYSTAL CITY, VA SP AMER UROL ASSOC, AMER CANC SOC, NCI, AMER COLL SURGEONS COMMISS CANC DE PROSTATIC NEOPLASMS; NEOPLASM INVASIVENESS; NEOPLASM METASTASIS ID TUMOR VOLUME; UNTREATED PATIENTS; ADENOCARCINOMA; SERUM; HYPERPLASIA; MEN; DIFFERENTIATION; PROGRESSION; DISEASE AB Until recently, the only information on the growth rate of prostate tumors has been derived from cross-sectional histological labeling studies, autopsy data and clinical studies of patients managed expectantly. However, serial measurements of prostate specific antigen (PSA) may now allow studies of the natural history of the earliest stages of prostate cancer. Frozen sera samples from the Baltimore Longitudinal Study of Aging have been used to compare the patterns of change in PSA levels in men with and without prostate cancer up to 25 years before the diagnosis of cancer. Men with no prostatic disease exhibited a slow linear increase in PSA levels, whereas benign prostatic hyperplasia cases showed a gradual acceleration in the rate of change in PSA. In contrast, cancer cases exhibited an early linear phase followed by an exponential phase of increase in PSA levels before diagnosis. On average, the exponential phase of PSA increases began 7 to 9 years before the tumors were detected clinically. Thus, there is a significant window of opportunity for early detection of prostate cancer. The changes in PSA observed in men with and without prostate cancer are consistent with available information on prostatic growth and the long natural history of prostate cancer. A better understanding of the various factors that affect serum PSA levels may allow more effective use of PSA measurements to detect early stage tumors and predict the biological potential of a tumor. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT UROL,BALTIMORE,MD. JOHNS HOPKINS UNIV HOSP,JAMES BUCHANAN BRADY UROL INST,BALTIMORE,MD 21205. RP PEARSON, JD (reprint author), NIA,CTR GERONTOL RES,LONGITUDINAL STUDIES BRANCH,BALTIMORE,MD, USA. NR 31 TC 60 Z9 61 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 1994 VL 152 IS 5 BP 1743 EP 1748 PN 2 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA PL686 UT WOS:A1994PL68600019 PM 7523722 ER PT J AU HANKS, GE PEARSON, JD CATALONA, WJ LINEHAN, WM BAGSHAW, MA TRIBUKAIT, B LANGE, PH ADOLFSSON, J PAULSON, DF AF HANKS, GE PEARSON, JD CATALONA, WJ LINEHAN, WM BAGSHAW, MA TRIBUKAIT, B LANGE, PH ADOLFSSON, J PAULSON, DF TI DISCUSSION SO JOURNAL OF UROLOGY LA English DT Discussion C1 AMER COLL RADIOL,PHILADELPHIA,PA. MASSACHUSETTS GEN HOSP,BOSTON,MA. NIA,CTR GERONTOL RES,LONGITUDINAL STUDIES BRANCH,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,DEPT UROL,BALTIMORE,MD. JOHNS HOPKINS UNIV HOSP,JAMES BUCHANAN BRADY UROL INST,BALTIMORE,MD 21205. WASHINGTON UNIV,SCH MED,DIV UROL SURG,ST LOUIS,MO. STANFORD UNIV,SCH MED,DEPT RADIAT ONCOL,STANFORD,CA. UNIV WASHINGTON,SCH MED,DEPT UROL,SEATTLE,WA. KAROLINSKA HOSP,DEPT UROL,STOCKHOLM,SWEDEN. KAROLINSKA HOSP,DEPT PATHOL,CYTOL SECT,STOCKHOLM,SWEDEN. LINKOPING UNIV,DEPT HLTH & SOC,LINKOPING,SWEDEN. DUKE UNIV,MED CTR,DIV UROL SURG,DURHAM,NC. RP HANKS, GE (reprint author), FOX CHASE CANC CTR,DEPT RADIAT ONCOL,7701 BURHOLME AVE,PHILADELPHIA,PA 19111, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 1994 VL 152 IS 5 BP 1749 EP 1750 PN 2 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA PL686 UT WOS:A1994PL68600020 ER PT J AU SCARDINO, PT LITWIN, MS ANDRIOLE, GL MILES, BJ MENON, M AUSTENFELD, MS CATALONA, WJ GROSSMAN, HB BECK, JR WILT, TJ GOHAGAN, JK OLSSON, CA AF SCARDINO, PT LITWIN, MS ANDRIOLE, GL MILES, BJ MENON, M AUSTENFELD, MS CATALONA, WJ GROSSMAN, HB BECK, JR WILT, TJ GOHAGAN, JK OLSSON, CA TI DISCUSSION SO JOURNAL OF UROLOGY LA English DT Discussion ID PROSTATE-CANCER C1 UNIV CALIF LOS ANGELES, DEPT SURG, DIV UROL, LOS ANGELES, CA 90024 USA. WASHINGTON UNIV, SCH MED, DIV UROL SURG, ST LOUIS, MO 63110 USA. WASHINGTON UNIV, SCH MED, DIV LAB MED, ST LOUIS, MO 63110 USA. BAYLOR COLL MED, DEPT PATHOL, INFORMAT TECHNOL PROGRAM, HOUSTON, TX 77030 USA. UNIV KANSAS, MED CTR, UROL SECT, KANSAS CITY, KS 66103 USA. BROOKE ARMY MED CTR, DEPT SURG, UROL SERV, FT SAM HOUSTON, TX 78234 USA. UNIV UTAH, MED CTR, DIV UROL, SALT LAKE CITY, UT USA. WASHINGTON UNIV, SCH MED, DIV UROL SURG, ST LOUIS, MO 63110 USA. VET ADM MED CTR, DEPT MED, GEN INTERNAL MED SECT, MINNEAPOLIS, MN USA. UNIV MINNESOTA, MINNEAPOLIS, MN 55455 USA. VET ADM MED CTR, DEPT UROL, SEATTLE, WA 98108 USA. UNIV WASHINGTON, SEATTLE, WA 98195 USA. NCI, DIV CANC PREVENT & CONTROL, BETHESDA, MD 20892 USA. COLUMBIA UNIV, COLL PHYS & SURG,COLUMBIA PRESBYTERIAN MED CTR, SQUIER UROL CLIN,DEPT UROL, NEW YORK, NY 10032 USA. RP SCARDINO, PT (reprint author), BAYLOR COLL MED, DEPT UROL, INFORMAT TECHNOL PROGRAM, HOUSTON, TX 77030 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD NOV PY 1994 VL 152 IS 5 BP 1900 EP 1902 PN 2 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA PL686 UT WOS:A1994PL68600054 ER PT J AU GOHAGAN, JK PROROK, PC KRAMER, BS CORNETT, JE AF GOHAGAN, JK PROROK, PC KRAMER, BS CORNETT, JE TI PROSTATE-CANCER SCREENING IN THE PROSTATE, LUNG, COLORECTAL AND OVARIAN-CANCER SCREENING TRIAL OF THE NATIONAL-CANCER-INSTITUTE SO JOURNAL OF UROLOGY LA English DT Article; Proceedings Paper CT Conference on Detection and Treatment of Early Stage Prostate Cancer CY DEC 03-05, 1993 CL CRYSTAL CITY, VA SP AMER UROL ASSOC, AMER CANC SOC, NCI, AMER COLL SURGEONS COMMISS CANC DE PROSTATIC NEOPLASMS; ANTIGENS, NEOPLASM; CARCINOMA; DIAGNOSTIC TESTS, ROUTINE ID DIGITAL RECTAL EXAMINATION; RADICAL PROSTATECTOMY; ANTIGEN; ULTRASONOGRAPHY; SERUM; ADENOCARCINOMA; POPULATION; CARCINOMA; DISEASE AB Screening for prostate cancer and subsequent treatment is of unknown benefit but carries known treatment related morbidity and mortality risks. The recent enthusiasm for screening in. the United States contrasts sharply with the more cautious attitudes of the European and Canadian medical communities. Current data from screening series without randomization and controls are inadequate to determine screening benefit. The prostate, lung, colorectal and ovarian cancer (randomized, controlled) screening trial of the National Cancer Institute, to include 74,000 men (and 74,000 women) 60 to 74 years old, has a design power of 90% to determine a 20% reduction of prostate cancer mortality from a baseline and 3 subsequent annual screens using prostate specific antigen and digital rectal examination. Randomization of participants into this trial began on November 16, 1993. Ten screening centers nationwide, a coordinating center, a laboratory and a biorepository are participating under contract. RP GOHAGAN, JK (reprint author), NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892, USA. NR 38 TC 150 Z9 150 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 1994 VL 152 IS 5 BP 1905 EP 1909 PN 2 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA PL686 UT WOS:A1994PL68600056 PM 7523735 ER PT J AU CATALONA, WJ COCKETT, ATK GOHAGAN, JK WILT, TJ LANGE, PH CHODAK, GW OLSSON, CA MCCULLOUGH, DL PROROCK, PC BAGSHAW, MA SCARDINO, PT ANDRIOLE, GL RAMSEY, E KLEIN, EA BARRY, MJ MENON, M SMITH, AY CORREA, RJ SIMPSON, KN GRAYHACK, JT DEKERNION, JB KOONTZ, WW FEIGHTNER, JW HEMSTREET, GP AF CATALONA, WJ COCKETT, ATK GOHAGAN, JK WILT, TJ LANGE, PH CHODAK, GW OLSSON, CA MCCULLOUGH, DL PROROCK, PC BAGSHAW, MA SCARDINO, PT ANDRIOLE, GL RAMSEY, E KLEIN, EA BARRY, MJ MENON, M SMITH, AY CORREA, RJ SIMPSON, KN GRAYHACK, JT DEKERNION, JB KOONTZ, WW FEIGHTNER, JW HEMSTREET, GP TI DISCUSSION SO JOURNAL OF UROLOGY LA English DT Discussion ID LOCALIZED PROSTATE-CANCER C1 KAMAN SCI CORP, COLORADO SPRINGS, CO USA. NCI, DIV CANC PREVENT & CONTROL, BETHESDA, MD 20892 USA. VET ADM MED CTR, DEPT MED, GEN INTERNAL MED SECT, MINNEAPOLIS, MN USA. UNIV MINNESOTA, MINNEAPOLIS, MN 55455 USA. VET ADM MED CTR, DEPT UROL, SEATTLE, WA 98108 USA. UNIV WASHINGTON, DEPT UROL, SEATTLE, WA 98195 USA. COLUMBIA UNIV, COLL PHYS & SURG,COLUMBIA PRESBYTERIAN MED CTR, SQUIER UROL CLIN,DEPT UROL, NEW YORK, NY USA. STANFORD UNIV, SCH MED, DEPT RADIAT ONCOL, STANFORD, CA 94305 USA. BAYLOR COLL MED, DEPT UROL, HOUSTON, TX 77030 USA. WASHINGTON UNIV, SCH MED, DIV UROL SURG, ST LOUIS, MO 63110 USA. WASHINGTON UNIV, SCH MED, DEPT LAB MED, ST LOUIS, MO 63110 USA. MASSACHUSETTS GEN HOSP, CTR MED PRACTICE EVALUAT, BOSTON, MA 02114 USA. UNIV N CAROLINA, SCH PUBL HLTH, DEPT HLTH POLICY & ADM, CHAPEL HILL, NC USA. UNIV CALIF LOS ANGELES, DEPT SURG, DIV UROL, LOS ANGELES, CA 90024 USA. MCMASTER UNIV, DEPT FAMILY MED, HAMILTON L8S 4L8, ON, CANADA. STANFORD UNIV, SCH MED, DEPT RADIAT ONCOL, STANFORD, CA 94305 USA. RP CATALONA, WJ (reprint author), WASHINGTON UNIV, SCH MED, DIV UROL SURG, 4960 CHILDRENS PL, ST LOUIS, MO 63110 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD NOV PY 1994 VL 152 IS 5 BP 1915 EP 1921 PN 2 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA PL686 UT WOS:A1994PL68600058 ER PT J AU MOORE, JP WILLEY, RL LEWIS, GK ROBINSON, J SODROSKI, J AF MOORE, JP WILLEY, RL LEWIS, GK ROBINSON, J SODROSKI, J TI IMMUNOLOGICAL EVIDENCE FOR INTERACTIONS BETWEEN THE FIRST, 2ND, AND 5TH CONSERVED DOMAINS OF THE GP120 SURFACE GLYCOPROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO JOURNAL OF VIROLOGY LA English DT Article ID ENVELOPE GLYCOPROTEIN; MONOCLONAL-ANTIBODIES; VARIABLE REGIONS; PROTEIN SEQUENCES; SOLUBLE CD4; BINDING; HIV-1; GENE; ASSOCIATION; EPITOPES AB We have used a combination of genetic and immunological techniques to explore how amino acid substitutions in the second conserved (C2) domain of gp120 from human immunodeficiency virus type 1 (HIV-1) affect the conformation of the protein. It was reported previously (R. L. Willey, E. M. Ross, A. J. Buckler-White, T. S. Theodore, and M. A. Martin. J. Virol. 63:3595-3600, 1989) that an asparagine-glutamine (N/Q) substitution at C2 residue 267 of HIV-1 NL4/3 reduced virus infectivity, but that infectivity was restored by a compensatory amino acid change (serine-glutamine; S/N) at residue 128 in the C1 domain. Here we show that the 267 N/Q substitution causes the abnormal exposure of a segment of C1 spanning residues 80 to 120, which compromises the integrity of the CD4-binding site. The reversion substitution at residue 128 restores the normal conformation of the C1 domain and recreates a high-affinity CD4-binding site. The gp120 structural perturbation caused by changes in C2 extends also to the C5 domain, and we show by immunological analysis that there is a close association between areas of the C1 and C5 domains. This association might be important for forming a complex binding site for gp41 (E. Helseth, U. Olshevsky, C. Furman, and J. Sodroski. J. Virol. 65:2119-2123, 1991). Segments of the C1 and C2 domains are predicted to form amphipathic alpha helices. We suggest that these helices might be packed together in the core of the folded gp120 molecule, that the 267 N/Q substitution disrupts this interdomain association, and that the 128 S/N reversion substitution restores it. C1 NIAID,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,DEPT MICROBIOL & IMMUNOL,BALTIMORE,MD 21201. UNIV CONNECTICUT,DEPT PAEDIAT,STORRS,CT 06030. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. RP MOORE, JP (reprint author), NYU,SCH MED,AARON DIAMOND AIDS RES CTR,455 1ST AVE,NEW YORK,NY 10016, USA. FU NIAID NIH HHS [AI25862, AI30358, AI36082] NR 46 TC 77 Z9 77 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 NOV PY 1994 VL 68 IS 11 BP 6836 EP 6847 PG 12 WC Virology SC Virology GA PL736 UT WOS:A1994PL73600002 PM 7933065 ER PT J AU CHANG, YN KENAN, DJ KEENE, JD GATIGNOL, A JEANG, KT AF CHANG, YN KENAN, DJ KEENE, JD GATIGNOL, A JEANG, KT TI DIRECT INTERACTIONS BETWEEN AUTOANTIGEN LA AND HUMAN-IMMUNODEFICIENCY-VIRUS LEADER RNA SO JOURNAL OF VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; EPSTEIN-BARR VIRUS; SYSTEMIC LUPUS-ERYTHEMATOSUS; VESICULAR STOMATITIS-VIRUS; CELL NUCLEAR-PROTEIN; HIV-1 TAR RNA; 2 SMALL RNAS; BINDING PROTEIN; TRANS-ACTIVATION; POLYMERASE-III AB We have characterized the in vivo and in vitro binding of human La protein to the human immunodeficiency virus type 1 (HIV-1) leader RNA, the trans-activation response element (TAR). In immunoprecipitation studies using anti-La serum, La-TAR ribonucleoprotein; were recovered from HIV-1-infected lymphocytes. Further characterization of this interation revealed that La has preference for the TAR stem. However, TAR RNA recognition tolerated changes in the primary sequence of the stem as long as the secondary; structure was conserved. This structural aspect-of La-TAR recognition was confirmed in competition studies in which certain homopolymers influenced complex formation while other single-stranded and double-stranded RNAs had no effect. Deletion mutants of recombinant La protein were used to demonstrate that the residues responsible for binding to polymerase III precursor transcripts overlapped the binding domain for the TAR leader RNA. This finding;ling of a direct interaction between La and TAR has functional implications for translational regulation of HIV-1 mRNAs as demonstrate in the accompanying report (Y. V. Svitkin, A. Pause, and N. Sonenberg, J. Virol. 68:7001-7007, 1994). C1 NIAID, MOLEC MICROBIOL LAB, MOLEC VIROL SECT, BETHESDA, MD 20892 USA. DUKE UNIV, MED CTR, DEPT MICROBIOL, DURHAM, NC 27710 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 91 TC 101 Z9 102 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD NOV PY 1994 VL 68 IS 11 BP 7008 EP 7020 PG 13 WC Virology SC Virology GA PL736 UT WOS:A1994PL73600021 PM 7933083 ER PT J AU CHEN, DY ZENG, CQY WENTZ, MJ GORZIGLIA, M ESTES, MK RAMIG, RF AF CHEN, DY ZENG, CQY WENTZ, MJ GORZIGLIA, M ESTES, MK RAMIG, RF TI TEMPLATE-DEPENDENT, IN-VITRO REPLICATION OF ROTAVIRUS RNA SO JOURNAL OF VIROLOGY LA English DT Article ID DOUBLE-STRANDED-RNA; TEMPERATURE-SENSITIVE MUTANTS; SINGLE-SHELLED PARTICLES; L-A-VIRUS; INVITRO TRANSCAPSIDATION; NUCLEOTIDE-SEQUENCE; SA11; EXPRESSION; PROTEINS; GENOME AB A template-dependent, in vitro rotavirus RNA replication system was established. The system initiated and synthesized full-length double-stranded RNAs on rotavirus positive-sense template RNAs. Native rotavirus mRNAs or in vitro transcripts, with bona fide 3' and 5' termini, derived from rotavirus cDNAs functioned as templates. Replicase activity was associated with a subviral particle containing VP1, VP2, and VP3 and was derived from native virions or baculovirus coexpression of rotavirus genes. A cis-acting signal involved in replication was localized within the 26 3'-terminal nucleotides of a reporter template RNA. Various biochemical and biophysical parameters affecting the efficiency of replication were examined to optimize the replication system. A replication system capable of in vitro initiation has not been previously described for Reoviridae. C1 BAYLOR COLL MED,DIV MOLEC VIROL,HOUSTON,TX 77030. NIH,INFECT DIS LAB,BETHESDA,MD 20892. FU NIAID NIH HHS [AI 16687]; NIDDK NIH HHS [DK 30144] NR 38 TC 75 Z9 81 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 NOV PY 1994 VL 68 IS 11 BP 7030 EP 7039 PG 10 WC Virology SC Virology GA PL736 UT WOS:A1994PL73600023 PM 7933085 ER PT J AU CHERNOMORDIK, L CHANTURIYA, AN SUSSTOBY, E NORA, E ZIMMERBERG, J AF CHERNOMORDIK, L CHANTURIYA, AN SUSSTOBY, E NORA, E ZIMMERBERG, J TI AN AMPHIPATHIC PEPTIDE FROM THE C-TERMINAL REGION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS ENVELOPE GLYCOPROTEIN CAUSES PORE FORMATION IN MEMBRANES SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 TRANSMEMBRANE PROTEIN; LIPID BILAYERS; CELL-MEMBRANE; ION CHANNELS; TYPE-1; CYTOPATHOGENICITY; MONOLAYERS; EXPRESSION; MECHANISM; SEGMENTS AB The peptide fragment of the carboxy-terminal region of the human immunodeficiency virus (HIV) transmembrane protein (gp41) has been implicated in T-cell death. This positively charged, amphipathic helix (amino acids 828 to 848) of the envelope protein is located within virions or cytoplasm. We studied the interaction of the isolated, synthetic amphipathic helix of gp41 with planar phospholipid bilayer membranes and with Sf9 cells using voltage clamp, potentiodynamic, and single-cell recording techniques. We found that the peptide binds strongly to planar membranes, especially to the negatively charged phosphatidylserine bilayer. In the presence of micromolar concentrations of peptide sufficient to make its surface densities comparable,vith those of envelope glycoprotein molecules in HIV virions, an increase in bilayer conductance and a decrease in bilayer stability were observed, showing pore formation in the planar lipid bilayers. These pores were permeable to both monovalent and divalent cations, as well as to chloride. The exposure of the inner leaflet of cell membranes to even 25 nM peptide increased membrane conductance. We suggest that the carboxy terminal fragment of the HIV type 1 envelope protein may interact,vith the cell membrane of infected T cells to create lipidic pores which increase membrane permeability, leading to sodium and calcium flux into cells, osmotic swelling, and T-cell necrosis or apoptosis. C1 NICHHD, THEORET & PHYS BIOL LAB, BETHESDA, MD 20892 USA. NR 47 TC 89 Z9 90 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1994 VL 68 IS 11 BP 7115 EP 7123 PG 9 WC Virology SC Virology GA PL736 UT WOS:A1994PL73600033 PM 7933093 ER PT J AU MOMOEDA, M KAWASE, M JANE, SM MIYAMURA, K YOUNG, NS KAJIGAYA, S AF MOMOEDA, M KAWASE, M JANE, SM MIYAMURA, K YOUNG, NS KAJIGAYA, S TI THE TRANSCRIPTIONAL REGULATOR YY1 BINDS TO THE 5'-TERMINAL REGION OF B19 PARVOVIRUS AND REGULATES P6 PROMOTER ACTIVITY SO JOURNAL OF VIROLOGY LA English DT Article ID SERUM RESPONSE FACTOR; COLI RNA-POLYMERASE; NF-E1 YY-1; C-MYC; PROTEIN; SEQUENCE; DNA; GENOME; INVITRO; IDENTIFICATION AB We performed a systematic study to identify cellular factors that bound to the terminal repeat region of B19 parvovirus. Using electrophoretic mobility shift assays; we detected one cellular factor which prominently bound to the repeat region. The factor was purified from K562 nuclear extract by specific DNA affinity column chromatography and identified as YY1, a multifunctional transcription factor. Of multiple possible YY1 binding sites in the upstream region of the P6 promotes, three showed specific strong binding. Transcription enhancement by YY1 was demonstrated in vitro by transient transfection assays. In studies using truncated and mutated versions of this region, YY1 activity was diminished by the alteration of any two of these three sites and abolished by the alteration of all three sites. Our results suggest that YY1 is a positive regulator of B19 parvovirus transcription. C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. RI Jane, Stephen/D-6659-2011 NR 46 TC 30 Z9 30 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 NOV PY 1994 VL 68 IS 11 BP 7159 EP 7168 PG 10 WC Virology SC Virology GA PL736 UT WOS:A1994PL73600038 PM 7933098 ER PT J AU RODEN, RBS KIRNBAUER, R JENSON, AB LOWY, DR SCHILLER, JT AF RODEN, RBS KIRNBAUER, R JENSON, AB LOWY, DR SCHILLER, JT TI INTERACTION OF PAPILLOMAVIRUSES WITH THE CELL-SURFACE SO JOURNAL OF VIROLOGY LA English DT Article ID VIRUS-LIKE PARTICLES; CERVICAL INTRAEPITHELIAL NEOPLASIA; ANTIBODY-MEDIATED NEUTRALIZATION; COTTONTAIL RABBIT PAPILLOMAVIRUS; HEPARAN-SULFATE; L1 PROTEIN; INFECTION; BOVINE; INVITRO; TYPE-11 AB To initiate an investigation of the initial step in papillomavirus infection, we have examined the interaction of bovine papillomavirus type 1 (BPV) virions with C127 cells by two assays, binding of radioiodinated BPV virions to cell monolayers and BPV-induced focal transformation. Under physiological conditions, the labeled virions bound to the cell surface in a dose-dependent manner within 1 h. Antibody studies indicated that the interaction was specific and related to infectivity: polyclonal sera raised to BPV virions or to baculovirus-expressed BPV L1 virus-like particles (VLPs) inhibited BPV binding and focal transformation, while sera to denatured BPV virions, to denatured BPV L1, or to human papillomavirus type 16 (HPV-16) VLPs were not inhibitory. An exception was that antisera to BPV L2 were neutralizing but did not inhibit binding. Unlabeled BPV virions and BPV VLPs competed with binding to the cell surface in a concentration-dependent manner. Binding to the cell surface appeared to depend primarily on L1, since BPV VLPs composed of L1 alone or of L1/L2 were equally effective in inhibiting binding and focal transformation. VLPs of HPV-16 also inhibited BPV binding and BPV transformation of C127 cells, suggesting that they interact with the same cell surface molecule(s) as BPV virions. Radiolabeled BPV bound specifically to several mammalian cell lines of fibroblastic and epithelial origin, as well as to a human schwannoma and melanoma lines, although some lines bound up to 10 times as many counts as others. Radiolabeled HPV-16 VLPs bound to both human keratinocytes and mouse C127 cells. The results suggest that papillomaviruses bind a widely expressed and evolutionarily conserved cell surface receptor. C1 GEORGETOWN UNIV,SCH MED,DEPT PATHOL,WASHINGTON,DC 20007. RP RODEN, RBS (reprint author), NCI,CELLULAR ONCOL LAB,BLDG 36,ROOM 1D-19,BETHESDA,MD 20892, USA. NR 41 TC 123 Z9 129 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 NOV PY 1994 VL 68 IS 11 BP 7260 EP 7266 PG 7 WC Virology SC Virology GA PL736 UT WOS:A1994PL73600049 PM 7933109 ER PT J AU GAO, F YUE, L ROBERTSON, DL HILL, SC HUI, HX BIGGAR, RJ NEEQUAYE, AE WHELAN, TM HO, DD SHAW, GM SHARP, PM HAHN, BH AF GAO, F YUE, L ROBERTSON, DL HILL, SC HUI, HX BIGGAR, RJ NEEQUAYE, AE WHELAN, TM HO, DD SHAW, GM SHARP, PM HAHN, BH TI GENETIC DIVERSITY OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-2 - EVIDENCE FOR DISTINCT SEQUENCE SUBTYPES WITH DIFFERENCES IN VIRUS BIOLOGY SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; INFECTIOUS MOLECULAR CLONE; T-LYMPHOTROPIC RETROVIRUS; HIGHLY DIVERGENT; GUINEA-BISSAU; WEST-AFRICA; NUCLEOTIDE-SEQUENCE; HOSPITALIZED-PATIENTS; GENOME ORGANIZATION; PRIMATE LENTIVIRUS AB The virulence properties of human immunodeficiency virus type 2 (HIV-2) are known to vary significantly and to range from relative attenuation in certain individuals to high level pathogenicity in others. These differences in clinical manifestations may, at least in part, be determined by genetic differences among infecting virus strains. Evaluation of the full spectrum of HIV-2 genetic diversity is thus a necessary first step towards understanding its molecular epidemiology, natural history of infection, and biological diversity. In this study, we have used nested PCR techniques to amplify viral sequences from the DNA of uncultured peripheral blood mononuclear cells from 12 patients with HIV-2 seroreactivity. Sequence analysis of four nonoverlapping genomic regions allowed a comprehensive analysis of HIV-2 phylogeny. The results revealed (i) the existence of five distinct and roughly equidistant evolutionary lineages of HIV-2 which, by analogy with HIV-1, have been termed sequence subtypes A to E; (ii) evidence for a mosaic HIV-2 genome, indicating that coinfection with genetically divergent strains and recombination can occur in HIV-2-infected individuals; and (iii) evidence supporting the conclusion that some of the HIV-2 subtypes may have arisen from independent introductions of genetically diverse sooty mangabey viruses into the human population. Importantly, only a subset of HIV-2 strains replicated in culture: all subtype A viruses grew to high titers, but attempts to isolate representatives of subtypes C, D, and E, as well as the majority of subtype B viruses, remained unsuccessful. Infection with all five viral subtypes was detectable by commercially available serological (Western immunoblot) assays, despite intersubtype sequence differences of up to 25% in the gag, pol, and env regions. These results indicate that the genetic and biological diversity of HIV-2 is far greater than previously appreciated and suggest that there may be subtype-specific differences in virus biology. Systematic natural history studies are needed to determine whether this heterogeneity has clinical relevance and whether the various HIV-2 subtypes differ in their in vivo pathogenicity. C1 UNIV ALABAMA, DEPT MED, BIRMINGHAM, AL 35294 USA. UNIV ALABAMA, DEPT MICROBIOL, BIRMINGHAM, AL 35294 USA. UNIV NOTTINGHAM, QUEENS MED CTR, DEPT GENET, NOTTINGHAM NG7 2UH, ENGLAND. NCI, VIRAL EPIDEMIOL BRANCH, BETHESDA, MD USA. UNIV GHANA, SCH MED, DEPT MED, ACCRA, GHANA. SEROL INC, ATLANTA, GA USA. NYU, SCH MED, AARON DIAMOND AIDS RES CTR, NEW YORK, NY USA. RI Sharp, Paul/F-5783-2010 OI Sharp, Paul/0000-0001-9771-543X FU NIAID NIH HHS [P30 AI 27767, R01 AI 25219] NR 97 TC 268 Z9 273 U1 0 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD NOV PY 1994 VL 68 IS 11 BP 7433 EP 7447 PG 15 WC Virology SC Virology GA PL736 UT WOS:A1994PL73600069 PM 7933127 ER PT J AU CHIORINI, JA WIENER, SM OWENS, RA KYOSTIO, SRM KOTIN, RM SAFER, B AF CHIORINI, JA WIENER, SM OWENS, RA KYOSTIO, SRM KOTIN, RM SAFER, B TI SEQUENCE REQUIREMENTS FOR STABLE BINDING AND FUNCTION OF REP68 ON THE ADENOASSOCIATED VIRUS TYPE-2 INVERTED TERMINAL REPEATS SO JOURNAL OF VIROLOGY LA English DT Article ID INHIBITS CELLULAR-TRANSFORMATION; DOMINANT-NEGATIVE MUTANT; ADENOASSOCIATED VIRUS; DNA-REPLICATION; WILD-TYPE; BOVINE PAPILLOMAVIRUS; GEL-ELECTROPHORESIS; VIRAL REPLICATION; ESCHERICHIA-COLI; GENE-EXPRESSION AB Replication of the palindromic inverted terminal repeats (ITRs) of adeno-associated virus type 2 requires several functions of the viral nonstructural Rep proteins. These include binding to the ITR, nicking of the double-stranded replication intermediate at the terminal resolution site (trs), and then strand displacement and synthesis from the nick. This report demonstrates the ability of both recombinant fusion maltose-binding protein (MBP)-Rep68 Delta produced in Escherichia coli and wild-type (wt) Rep68 to bind to a linear truncated form of the ITR, Delta 57 ITR, with similar affinity as to the wt hairpin ITR. A dissociation constant for MBP-Rep68 Delta of approximately 8 x 10(-10) M was determined for the wt ITR and Delta 57 ITR probes. Truncation of Delta 57 ITR to generate Delta 28 ITR, which retains the GCTC repeat motif but not the trs, bound at least 10 times less efficiently than Delta 57 ITR. Extension of Delta 28 ITR with nonspecific sequence restored the ability of MBP-Rep68 Delta to bind to Delta 28 ITR. Thus, high-affinity binding would appear to require stabilization by banking sequence as well as the intact GCTC repeat motif. Cleavage of the Delta 57 ITR probe with DdeI, which truncates the flanking sequence and was previously shown to inhibit binding by Rep68, also inhibited the binding of MBP Rep68 Delta. The requirements for stable binding were further defined with a series of oligonucleotide probes which spanned the region protected by MBP-Rep78 in DNase I footprinting. The binding activity of either MBP-Rep68 Delta or wt Rep68 to hairpin ITR or Delta 57 ITR was indistinguishable. However, the binding activity of MBP-Rep68 Delta to DNA does not appear to correlate with trs endonuclease activity. The nicking and covalent linkage of MBP-Rep68 Delta to the nonhairpin Delta 57 ITR was approximately 100-fold less efficient than its linkage to a hairpin-containing ITR. Therefore, although the hairpin portion of the ITR does not appear to play a role in recognition and stabilization of MBP-Rep68 Delta binding, its presence does affect the trs cleavage activity of the protein. C1 NIDDK,MOLEC & CELLULAR BIOL LAB,BETHESDA,MD 20892. GENET THERAPY INC,GAITHERSBURG,MD. RP CHIORINI, JA (reprint author), NHLBI,MOLEC HEMATOL BRANCH,BLDG 10 7D18,10 CTR DR,MSC 1654,BETHESDA,MD 20892, USA. RI kotin, robert/B-8954-2008 NR 49 TC 85 Z9 86 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 NOV PY 1994 VL 68 IS 11 BP 7448 EP 7457 PG 10 WC Virology SC Virology GA PL736 UT WOS:A1994PL73600070 PM 7933128 ER PT J AU KOHNO, S FUJIMURA, T SHEN, RL KWONCHUNG, KJ AF KOHNO, S FUJIMURA, T SHEN, RL KWONCHUNG, KJ TI DOUBLE-STRANDED-RNA VIRUS IN THE HUMAN PATHOGENIC FUNGUS BLASTOMYCES-DERMATITIDIS SO JOURNAL OF VIROLOGY LA English DT Note ID SACCHAROMYCES-CEREVISIAE; YEAST; PARTICLES; ORIGIN; SYSTEM AB Double-stranded RNA viruses were detected in a strain of Blastomyces dermatitidis isolated from a patient in Uganda. The viral particles are spherical (mostly 44 to 50 nm in diameter) and consist of about 25% double-stranded RNA (5 kb) and 75% protein (90 kDa). The virus contains transcriptional RNA polymerase activity; it synthesized single-stranded RNA in vitro in a conservative manner. The newly synthesized single-stranded RNA was a full-length strand, and the rate of chain elongation was approximately 170 nucleotides per min. The virus-containing strain shows no morphological difference from virus-free strains in the mycelial phase. Although the association with the presence of the virus is unclear, the virus-infected strain converts to the yeast form at 37 degrees C, but the yeast cells fail to multiply at that temperature. C1 NIDDK,BIOCHEM PHARMACOL LAB,GENET SIMPLE EUKARYOTES SECT,BETHESDA,MD. NCI,FREDERICK CANC RES & DEV CTR,MATH BIOL LAB,MEMBRANE BIOL SECT,FREDERICK,MD 21701. RP KOHNO, S (reprint author), NIAID,CLIN INVEST LAB,CLIN MYCOL SECT,11C 304,BLDG 10,BETHESDA,MD 20892, USA. RI Shen, Rulong/E-4079-2011; Fujimura, Tsutomu/K-5807-2014 OI Fujimura, Tsutomu/0000-0002-9457-6769 NR 36 TC 4 Z9 4 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 NOV PY 1994 VL 68 IS 11 BP 7554 EP 7558 PG 5 WC Virology SC Virology GA PL736 UT WOS:A1994PL73600084 PM 7933142 ER PT J AU RODEN, RBS WEISSINGER, EM HENDERSON, DW BOOY, F KIRNBAUER, R MUSHINSKI, JF LOWY, DR SCHILLER, JT AF RODEN, RBS WEISSINGER, EM HENDERSON, DW BOOY, F KIRNBAUER, R MUSHINSKI, JF LOWY, DR SCHILLER, JT TI NEUTRALIZATION OF BOVINE PAPILLOMAVIRUS BY ANTIBODIES TO L1 AND L2 CAPSID PROTEINS SO JOURNAL OF VIROLOGY LA English DT Note ID COTTONTAIL RABBIT PAPILLOMAVIRUS; VIRUS-LIKE PARTICLES; MONOCLONAL-ANTIBODIES; MEDIATED NEUTRALIZATION; IDENTIFICATION; EPITOPES; BPV-1; CELLS AB We have generated four mouse monoclonal antibodies (MAbs) to bovine papillomavirus virions that bound type-specific, adjacent, and conformationally dependent epitopes on the L1 major capsid protein. All four MAbs were neutralizing at ratios of 1 MAb molecule per 5 to 25 L1 molecules, but only three effectively blocked binding of the virus to the cell surface. Therefore, antibodies can prevent papillomavirus infection by at least two mechanisms: inhibition of cell surface receptor binding and a subsequent step in the infectious pathway. The neutralizing epitopes of the bovine papillomavirus L2 minor capsid protein were mapped to the N-terminal half of L2 by blocking the neutralizing activity of full-length L2 antiserum with bacterially expressed peptides of L2. In addition, rabbit antiserum raised against amino acids 45 to 173 of L2 had a neutralizing titer of 1,000, confirming that at least part of the N terminus of L2 is exposed on the virion surface. C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. NCI,GENET LAB,BETHESDA,MD 20892. NIAMS,STRUCT BIOL LAB,BETHESDA,MD 20892. NR 20 TC 132 Z9 136 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 NOV PY 1994 VL 68 IS 11 BP 7570 EP 7574 PG 5 WC Virology SC Virology GA PL736 UT WOS:A1994PL73600087 PM 7523700 ER PT J AU HOSHINO, Y KAPIKIAN, AZ CHANOCK, RM AF HOSHINO, Y KAPIKIAN, AZ CHANOCK, RM TI SELECTION OF COLD-ADAPTED MUTANTS OF HUMAN ROTAVIRUSES THAT EXHIBIT VARIOUS DEGREES OF GROWTH RESTRICTION IN-VITRO SO JOURNAL OF VIROLOGY LA English DT Note ID REASSORTANT ROTAVIRUSES; MONOCLONAL-ANTIBODIES; VACCINE CANDIDATES; RHESUS ROTAVIRUS; VIRUS-VACCINES; INFANTS; NEUTRALIZATION; VP7; SPECIFICITIES; SEROTYPE-1 AB Group A human rotavirus strains D, Wa, DS-1, and P were originally recovered from children with diarrhea. In an attempt to attenuate virulent, wild-type human rotaviruses of major epidemiological importance for use in a live oral vaccine, two reference rotavirus strains, D and DS-1, and two laboratory-generated reassortants, Wa x DS-1 and Wa x P, were subjected to cold adaptation. Collectively, these viruses provide antigenic coverage for both of the clinically important rotavirus VP4 antigens and three of the four important rotavirus VP7 antigens. Mutants of each of these rotaviruses were selected during successive serial passage in primary African green monkey kidney cells at progressively lower suboptimal temperatures (30, 28; and 26 degrees C). The genotype of each mutant appeared to be indistinguishable from that of its wild-type, parental virus. The mutants recovered after 10 serial passages at 30 degrees C exhibited both temperature sensitivity of plaque formation (i.e., a ts phenotype)and the ability to form plaques efficiently at suboptimal temperature (i.e., a cold adaptation [ca] phenotype), in contrast to parental wild-type rotavirus. The succeeding set of 10 serial passages at 28 degrees C selected mutants that exhibited an increased degree of cold adaptation, and three of the mutants exhibited an associated increase in temperature sensitivity. Finally, in the case of three of the strains, the third successive serial passage series, which was performed at 26 degrees C, selected for mutants with an even greater degree of cold adaptation than the previous series and was associated with greater temperature sensitivity in one instance. It appeared that each of the viruses sustained a minimum of four to five mutations during the total selection procedure. The ultimate identification of candidate vaccine viruses that exhibit the desired level of attenuation, immunogenicity, and protective efficacy needed for immunoprophylaxis will require clinical evaluation of these mutants in susceptible humans. RP HOSHINO, Y (reprint author), NIAID,INFECT DIS LAB,EPIDEMIOL SECT,9000 ROCKVILLE PIKE,BLDG 7,ROOM 105,BETHESDA,MD 20892, USA. NR 26 TC 10 Z9 11 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 NOV PY 1994 VL 68 IS 11 BP 7598 EP 7602 PG 5 WC Virology SC Virology GA PL736 UT WOS:A1994PL73600092 PM 7933149 ER PT J AU TOBIN, GJ SOWDER, RC FABRIS, D HU, MY BATTLES, JK FENSELAU, C HENDERSON, LE GONDA, MA AF TOBIN, GJ SOWDER, RC FABRIS, D HU, MY BATTLES, JK FENSELAU, C HENDERSON, LE GONDA, MA TI AMINO-ACID-SEQUENCE ANALYSIS OF THE PROTEOLYTIC CLEAVAGE PRODUCTS OF THE BOVINE IMMUNODEFICIENCY VIRUS GAG PRECURSOR POLYPEPTIDE SO JOURNAL OF VIROLOGY LA English DT Note ID MURINE LEUKEMIA-VIRUS; BIOLOGICALLY-ACTIVE PROVIRUSES; GENE-PRODUCTS; POSTTRANSLATIONAL MODIFICATIONS; NUCLEOTIDE-SEQUENCE; MOLECULAR-CLONING; PROTEINS; TYPE-1; IDENTIFICATION; MORPHOGENESIS AB Bovine immunodeficiency virus Gag proteins were purified from virions, and their amino acid sequences and molecular masses were determined. The matrix, capsid, and nucleocapsid (MA, CA, and NC, respectively) and three smaller proteins (p2L, p3, and p2) were found to have molecular masses of 14.6, 24.6, and 7.3 and 2.5, 2.7, and 1.9 kDa, respectively. The order of these six proteins in the Gag precursor, Pr53(gag), is NH2-MA-p2L-CA-p3-NC-p2-COOH. In contrast to other retroviral MA proteins, the bovine immunodeficiency virus MA retains its N-terminal methionine and is not modified by fatty acids. In addition, the bovine immunodeficiency virus NC migrates as a 13-kDa protein in denaturing gel electrophoresis; however, its molecular mass was determined to be 7.3 kDa. C1 NCI,FREDERICK CANC RES & DEV CTR,CELL & MOLEC STRUCT LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,AIDS VACCINE PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702. UNIV MARYLAND,DEPT CHEM & BIOCHEM,BALTIMORE,MD 21218. NR 44 TC 23 Z9 24 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 NOV PY 1994 VL 68 IS 11 BP 7620 EP 7627 PG 8 WC Virology SC Virology GA PL736 UT WOS:A1994PL73600096 PM 7933153 ER PT J AU XU, LC YOUNG, HA BLANCO, M KESSLER, S ROBERTS, AB KARLSSON, S AF XU, LC YOUNG, HA BLANCO, M KESSLER, S ROBERTS, AB KARLSSON, S TI POOR TRANSDUCTION EFFICIENCY OF HUMAN HEMATOPOIETIC PROGENITOR CELLS BY A HIGH-TITER AMPHOTROPIC RETROVIRUS PRODUCER CELL CLONE SO JOURNAL OF VIROLOGY LA English DT Note ID TRANSFORMING GROWTH-FACTOR; HUMAN GENE-THERAPY; HUMAN-BONE MARROW; FACTOR-BETA; HUMAN GLUCOCEREBROSIDASE; MACROPHAGES; EXPRESSION; INFECTION; SAFE; LINE AB The transduction efficiency of human bone marrow CD34(+) cells with supernatants from the retrovirus producer cell clone PA317/LGSN 16 was only one fifth of that with supernatants from GP+envAm12/LGSN 15, even though both producers had similar infection titers on 3T3 cells. PA317/LGSN 16-conditioned medium inhibited the proliferation of the bone marrow CD34(+) cells, and this inhibitory effect was partially blocked by anti-transforming growth factor beta antibodies. These studies suggest that cytokine secretion plays a role in the suppression of retrovirus transduction of human CD34(+) cells. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. SYSTEMIX,PALO ALTO,CA 94304. RP XU, LC (reprint author), NINCDS,DEV & METAB NEUROL BRANCH,MED & MOLEC GENET SECT,BLDG 10,ROOM 3D04,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 17 TC 18 Z9 18 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 NOV PY 1994 VL 68 IS 11 BP 7634 EP 7636 PG 3 WC Virology SC Virology GA PL736 UT WOS:A1994PL73600098 PM 7523701 ER PT J AU AFSHARI, CA BIVINS, HM BARRETT, JC AF AFSHARI, CA BIVINS, HM BARRETT, JC TI UTILIZATION OF A FOS-LACZ PLASMID TO INVESTIGATE THE ACTIVATION OF C-FOS DURING CELLULAR SENESCENCE AND OKADAIC ACID-INDUCED APOPTOSIS SO JOURNALS OF GERONTOLOGY LA English DT Article ID TRANSCRIPTION FACTOR AP-1; GROWTH-FACTORS; HUMAN-FIBROBLASTS; PROTO-ONCOGENE; DNA-SYNTHESIS; PREMATURE MITOSIS; GENE-EXPRESSION; TUMOR PROMOTER; HAMSTER-CELLS; 3T3 CELLS AB C-fos is an immediate-early gene that is induced by external stimuli and is possibly involved in initiation of DNA synthesis by such stimuli. In these studies, we used the murine c-fos promoter coupled to a lacZ reporter gene to study fos induction in senescent and quiescent cells. In transfected, quiescent, immortal Syrian hamster embryo (SHE) cells (10W), serum stimulation induced the expression of the fos construct to the same extent that DNA synthesis was stimulated. In contrast, in transfected normal cells that have a finite life span, we observed that the cells failed to display upregulation of fos lacz in response to serum in individual cells as they senesced. High doses of the phosphatase inhibitor okadaic acid (160-1000 nM) also induced fos-lacZ expression in quiescent immortal cells; however, induction of DNA synthesis and expression of fos-lacZ were not coordinately induced as a function of okadaic acid concentration. Low concentrations of okadaic acid (0.16 nM) induced DNA synthesis but not fos-lacZ expression, indicating that induction of DNA synthesis by phosphatase inhibitors may bypass, at least quantitatively, the requirement for c-fos induction. At the levels of okadaic acid that induced fos-lacZ expression, cell death, rather than DNA synthesis, was observed. The cells died by apoptosis, thereby implicating a signaling pathway that includes c-fos induction in this process. C1 NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,CURRICULUM TOXICOL,CHAPEL HILL,NC. NR 49 TC 18 Z9 18 U1 1 U2 4 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD NOV PY 1994 VL 49 IS 6 BP B263 EP B269 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA PR342 UT WOS:A1994PR34200014 PM 7525690 ER PT J AU WILSON, PWF ANDERSON, KM HARRIS, T KANNEL, WB CASTELLI, WP AF WILSON, PWF ANDERSON, KM HARRIS, T KANNEL, WB CASTELLI, WP TI DETERMINANTS OF CHANGE IN TOTAL CHOLESTEROL AND HDL-C WITH AGE - THE FRAMINGHAM-STUDY SO JOURNALS OF GERONTOLOGY LA English DT Article ID CORONARY HEART-DISEASE; LEAN BODY-MASS; LIPOPROTEIN CHOLESTEROL; SERUM-CHOLESTEROL; WEIGHT-LOSS; OVERWEIGHT MEN; RISK FACTOR; PEOPLE; WOMEN; EXERCISE AB Objective: The purpose of the study was to assess the determinants of change of total cholesterol and high density lipoprotein cholesterol (HDL-C) change in an adult population. Methods. The prospective cohort was examined at baseline and eight. years later. A total of 2,222 men and 2,677 women age 20-79 years at baseline were included. Analyses were performed in 15-year age groups, and persons with cardiovascular disease or cancer during the observation period were excluded. Results. In longitudinal analyses, body mass index (BMI) and plasma total cholesterol levels of each rose in concert among younger age groups, whereas levels declined in older individuals. Mean levels of BMI and total cholesterol peaked at a later age in women than in men. The corresponding changes in HDL-C were negative at all ages, and greater declines were seen in the elderly. A decrease in plasma total cholesterol was highly associated with greater age and a decrease in body mass index over the study interval, whereas the decline in HDL-C was proportional to change in body mass index. These changes remained significant after adjustment for baseline age and change in alcohol intake, cigarette consumption, diuretic use, and oral estrogen use. Conclusions. The rise in plasma total cholesterol among apparently healthy young men and women and its fall in the elderly are significantly associated with similar trends for obesity. The key determinants of a decline in HDL-C are an increase in obesity and advancing age itself. A decline in total cholesterol and in HDL-C is particularly common among the elderly, and it can be expected to occur without specific dietary or pharmacologic intervention. C1 CENTOCOR INC,MALVERN,PA 19355. NIA,BETHESDA,MD 20892. RP WILSON, PWF (reprint author), FRAMINGHAM HEART DIS EPIDEMIOL STUDY,5 THURBER ST,FRAMINGHAM,MA 01701, USA. NR 37 TC 100 Z9 105 U1 1 U2 6 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD NOV PY 1994 VL 49 IS 6 BP M252 EP M257 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA PR342 UT WOS:A1994PR34200019 PM 7963277 ER PT J AU SEMINOMORA, MC LEONMONZON, ME DALAKAS, MC AF SEMINOMORA, MC LEONMONZON, ME DALAKAS, MC TI THE EFFECT OF L-CARNITINE ON THE AZT-INDUCED DESTRUCTION OF HUMAN MYOTUBES .2. TREATMENT WITH L-CARNITINE IMPROVES THE AZT-INDUCED CHANGES AND PREVENTS FURTHER DESTRUCTION SO LABORATORY INVESTIGATION LA English DT Article DE ZIDOVUDINE; MUSCLE MITOCHONDRIA; LIPID DROPLETS ID HUMAN-IMMUNODEFICIENCY-VIRUS; MITOCHONDRIAL-DNA; MUSCLE MITOCHONDRIA; ZIDOVUDINE THERAPY; MYOPATHY; SKELETAL; INHIBITION; ANALOGS; CELLS; AIDS AB BACKGROUND: Zidovudine (AZT) as used in the treatment of AIDS causes a mitochondrial myopathy characterized by enzymatic defects in the respiratory chain system, accumulation of lipid droplets, and carnitine deficiency. Human myotubes treated with AZT demonstrate abnormal mitochondria, accumulation of lipid, and increased lysosomes. Because L-carnitine plays a major role in the transport of long chain fatty acids across the inner mitochondrial membrane and facilitates the beta-oxidation of fatty acids, we examined whether L-carnitine can enhance the recovery of the affected myotubes after withdrawal of AZT and can improve the structural changes of the myotubes while AZT treatment continues. EXPERIMENTAL DESIGN: Myotubes, prepared from human muscle biopsies, were exposed to 250 mu M of AZT for 3 to 6 weeks. After 3 weeks of AZT treatment, the cultures were treated with L-carnitine or medium for 3 weeks, while AZT treatment was either withdrawn or continued for 3 more weeks. The cultures were evaluated with: (a) light microscopy; (b) immunocytochemistry, to count the number of myotubes stained with antibodies to Leu-le; (c) oil red O stain, to assess the lipid droplet accumulation; and (d) electron microscopy, to count all the organelles within representative sections of the myotubes, at x24,000, and to calculate the volumetric density (Vvi) of each organelle per unit volume of tissue. RESULTS: In the post-AZT-treated cultures, L-carnitine increased the number of Leu-19-positive myotubes from 3.83 +/- 1.23 to 23 +/- 1.5 per field, normalized their mitochondria, decreased the lipid droplets, and increased the Vvi of the myofibrils. In the cultures treated with 3 weeks of L-carnitine while AZT treatment continued for 3 more weeks, the number of myotubes increased from 3.3 +/- 0.74 to 6.87 +/- 1.35; the absolute number of the mitochondria increased from 1.65 +/- 0.35 to 9.02 +/- 1.11 and their Vvi from 3.67 +/- 0.83 to 6.57 +/- 0.78 (p < 0.05); the Vvi of the myofibrils increased from 2.50 +/- 0.52 to 5.37 +/- 0.76 (p < 0.05); and the Vvi of the lipid droplets decreased from 5.06 +/- 1.44 to 2.72 +/- 0.72 (p < 0.05). In the AZT-treated cultures that did not receive L-carnitine, the mitochondria demonstrated extensive vacuolation, abnormal cristae, and paracrystalline inclusions; in contrast, in the L-carnitine-treated cultures, the mitochondria had substantially improved in spite of continuation of AZT. CONCLUSIONS: L-carnitine enhances the pace and degree of recovery of the AZT-associated destruction of human myotubes, restores and preserves the structure of mitochondria, mobilizes the endomyotubular fat, and allows the regeneration of myofibrils, even if AZT treatment continues. The findings may have potential clinical implications in improving the myotoxicity of AZT in patients with AIDS when the administration of AZT treatment must continue. C1 NINCDS,MED NEUROL BRANCH,NEUROMUSCULAR DIS SECT,BETHESDA,MD 20892. NR 31 TC 45 Z9 47 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD NOV PY 1994 VL 71 IS 5 BP 773 EP 781 PG 9 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA PV926 UT WOS:A1994PV92600018 PM 7967528 ER PT J AU SARIG, S WEISS, TA KATZ, I KAHANA, F AZOURY, R OKON, E KRUTH, HS AF SARIG, S WEISS, TA KATZ, I KAHANA, F AZOURY, R OKON, E KRUTH, HS TI DETECTION OF CHOLESTEROL ASSOCIATED WITH CALCIUM MINERAL USING CONFOCAL FLUORESCENCE MICROSCOPY SO LABORATORY INVESTIGATION LA English DT Article DE ATHEROSCLEROSIS; CALCIFICATION; FILIPIN ID HUMAN ATHEROSCLEROTIC LESIONS; PREVENTION; DEPOSITS; PLAQUES; APATITE; AORTA AB BACKGROUND: Cholesterol and calcium are prominant components within human atherosclerotic lesions. Both accumulate predominantly within the central core region of lesions. Because of similarities in some crystallographic faces of cholesterol monohydrate and calcium apatite, it has been previously proposed that deposition of one may nucleate the deposition of the other. EXPERIMENTAL DESIGN: In this study, we have used the technique of confocal fluorescence microscopy to assess the spatial orientation of cholesterol in association with calcium mineral. Localization of cholesterol within mineral was carried out by staining cholesterol with the fluorescent probe, filipin. RESULTS: With this technique, it was possible to localize cholesterol associated with the surface of hydroxyapatite seeds, cholesterol incorporated within calcium phosphate-cholesterol agglomerates produced irt vitro, and cholesterol within apatite isolated from human atherosclerotic lesions. CONCLUSIONS: The presence of cholesterol within the center of calcified granules from atherosclerotic plaque suggests that cholesterol or associated lipids may act to nucleate the deposition of apatite. Confocal fluorescence microscopy should be a useful technique by which to study the relationship of cholesterol associated with calcium minerals that occur not only in atherosclerotic blood vessels, but also in gallstones, and calcified cardiac valves. C1 NHLBI,EXPTL ATHEROSCLEROSIS SECT,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,GRAD SCH APPL SCI & TECHNOL,CASALI INST APPL CHEM,IL-91904 JERUSALEM,ISRAEL. SOREQ NUCL RES CTR,DEPT RADIOPHARMACEUT,YAVNE,ISRAEL. HADASSAH HEBREW UNIV HOSP,DEPT PATHOL,JERUSALEM,ISRAEL. HADASSAH HEBREW UNIV HOSP,DEPT CARDIOL,JERUSALEM,ISRAEL. NR 17 TC 49 Z9 49 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD NOV PY 1994 VL 71 IS 5 BP 782 EP 787 PG 6 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA PV926 UT WOS:A1994PV92600019 PM 7967529 ER PT J AU ADAMSON, PC AF ADAMSON, PC TI CLINICAL AND PHARMACOKINETIC STUDIES OF ALL-TRANS-RETINOIC ACID IN PEDIATRIC-PATIENTS WITH CANCER SO LEUKEMIA LA English DT Article ID HUMAN NEURO-BLASTOMA; ACUTE PROMYELOCYTIC LEUKEMIA; 13-CIS-RETINOIC ACID; HUMAN NEUROBLASTOMA; CELL-LINES; PHASE-I; DIFFERENTIATION; EXPRESSION; INVITRO; PHARMACOLOGY AB This review will summarize the rationale for pursuing investigations into the use of retinoids for pediatric patients with cancer, describe the phase I results of all-trans-retinoic acid (ATRA) in children, and discuss the results of a series of preclinical and clinical pharmacokinetic studies of ATRA. The prognosis for children with advanced stage neuroblastoma, the most common extracranial solid tumor of childhood, has remained poor despite significant increases in the intensity of multi-modality therapy. Observations that neuroblastoma has the potential in vivo to differentiate into the more mature neuronal phenotype of a ganglioneuroma or to spontaneously regress, combined with the ability of ATRA to induce differentiation of neuroblastoma cell lines in vitro, suggests that neuroblastoma may be a prime candidate for a retinoid-based approach to differentiation therapy. We previously performed a standard pediatric phase I trial of ATRA and defined the maximum tolerated dose (MTD) in children to be 60 mg/m(2)/day, significantly lower than the MTD in adult patients. Pharmacokinetic results revealed that the plasma half-life of ATRA was short (45 min) relative to 13-cis-RA (12-24 h), and that plasma drug exposure decreased significantly by day 28 of daily drug administration. Preclinical studies using an i.v. formulation of ATRA in a Rhesus monkey pharmacokinetic model then demonstrated that ATRA is eliminated by a capacity-limited (saturable) process. This elimination process was rapidly induced within the first week of daily i.v. ATRA administration, and suggested that an intermittent schedule of drug administration might allow for down-regulation of the elimination process. These pre-clinical studies formed the basis for investigating whether an intermittent schedule of ATRA administration would allow for repeated periods of relatively higher plasma drug concentrations. Preliminary results of two clinical trials using intermittent schedules of administration suggest that this approach may result in significantly higher plasma drug exposure over time. Plans to study the role of intermittent schedules of ATRA administration in pediatric phase II trials in patients with neuroblastoma are underway. RP ADAMSON, PC (reprint author), NCI,PEDIAT BRANCH,PHARMACOL EXPTL THERAPEUT SECT,BLDG 10,ROOM 13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 28 TC 10 Z9 10 U1 1 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD NOV PY 1994 VL 8 IS 11 BP 1813 EP 1816 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA PV836 UT WOS:A1994PV83600003 PM 7967727 ER PT J AU ADAMSON, PC POPLACK, DG BALIS, FM AF ADAMSON, PC POPLACK, DG BALIS, FM TI THE CYTOTOXICITY OF THIOGUANINE VS MERCAPTOPURINE IN ACUTE LYMPHOBLASTIC-LEUKEMIA SO LEUKEMIA RESEARCH LA English DT Article DE THIOPURINES; CHILDHOOD LEUKEMIA; SCHEDULE DEPENDENCE ID HAMSTER OVARY CELLS; CYTO-TOXICITY; THIOPURINE METHYLTRANSFERASE; DRUG SENSITIVITY; 6-MERCAPTOPURINE; 6-THIOGUANINE; CHILDHOOD; ASSAY; METABOLISM; PHARMACOLOGY AB The use of mercaptopurine (MP) rather than thioguanine (TG) in the treatment of childhood acute lymphoblastic leukemia (ALL) has occurred for historical reasons, but does not have a pharmacologic basis. The purpose of this study was to begin to address whether TG would be more efficacious than MP in the treatment of childhood ALL, Pre-clinical cytotoxicity studies were performed using human leukemic cell lines and leukemic cells from patients with ALL. First, the concentration-survival curves for MP and TG in three human leukemic cell lines (MOLT-4, CCRF-CEM and Wilson) were determined. The second group of experiments determined the concentration-time dependence for cytotoxicity of MP and TG. The final group of experiments compared the in vitro cytotoxicity of MP to TG in leukemic cells from patients with ALL. The thiopurines displayed classical anti-metabolite cytotoxicity profiles, exhibiting a cytotoxicity threshold concentration and demonstrating an increase in cell kill with prolongation of exposure to the drug. For MP, the cytotoxicity threshold was approximately 1 mu M, with maximum cytotoxicity occurring with 10 mu M concentrations. For TG, the threshold was only 0.05 mu M with maximum cytotoxicity occurring at 0.5 mu M. Exposure to MP for more than 8 h was necessary to produce cytotoxicity, whereas exposures as short as 4 h were required for TG. Leukemic cells from children with ALL were also more sensitive to TG than to MP. The median IC50 for TG (20 mu M) was significantly lower than that for MP (greater than or equal to 206 mu M). The data presented here provide a strong rationale for evaluating TG in place of MP in the treatment of childhood ALL. The more direct intracellular activation pathway, higher potency, and shorter duration of drug exposure necessary for cytotoxicity all suggest that TG may have an advantage over MP. RP ADAMSON, PC (reprint author), NCI,PEDIAT BRANCH,PHARMACOL & EXPTL THERAPEUT SECT,BLDG 10,ROOM 13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 46 TC 45 Z9 45 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD NOV PY 1994 VL 18 IS 11 BP 805 EP 810 DI 10.1016/0145-2126(94)90159-7 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA PR903 UT WOS:A1994PR90300002 PM 7967706 ER PT J AU IHDE, D BALL, D ARRIAGADA, R BARTHELEMY, N BENNER, S BONNER, J BUREAU, G CRINO, L DENEFFE, G EMAMI, B FELD, R JOSEPH, D PACCAGNELLA, A ROCMANS, P VANHOUTTE, P AF IHDE, D BALL, D ARRIAGADA, R BARTHELEMY, N BENNER, S BONNER, J BUREAU, G CRINO, L DENEFFE, G EMAMI, B FELD, R JOSEPH, D PACCAGNELLA, A ROCMANS, P VANHOUTTE, P TI POSTOPERATIVE ADJUVANT THERAPY FOR NONSMALL CELL LUNG-CANCER - A CONSENSUS REPORT SO LUNG CANCER LA English DT Article; Proceedings Paper CT 3rd IASLC Workshop on Therapy of Non-Small Cell Lung Cancer - Controversies in Staging and Treatment of Locally Advanced Non-Small Cell Lung Cancers CY AUG 29-SEP 02, 1993 CL BRUGGE, BELGIUM SP INT ASSOC STUDY LUNG CANC C1 PETER MACCALLUM CANC INST,MELBOURNE,VIC,AUSTRALIA. INST GUSTAVE ROUSSY,VILLEJUIF,FRANCE. UNIV LIEGE,LIEGE,BELGIUM. MD ANDERSON CANC CTR,HOUSTON,TX. MAYO CLIN & MAYO FDN,ROCHESTER,MN. GRP MED ST REMY,REIMS,FRANCE. OSPED POLICLIN,PERUGIA,ITALY. UNIV ZIEKENHUIS PELLENBERG,LUBBEEK,BELGIUM. WASHINGTON UNIV,ST LOUIS,MO. MT SINAI HOSP,TORONTO,ON,CANADA. GEELONG HOSP,GEELONG,VIC,AUSTRALIA. OSPED CIVILE,PADUA,ITALY. HOSP ERASME,BRUSSELS,BELGIUM. INST JULES BORDET,BRUSSELS,BELGIUM. RP IHDE, D (reprint author), NCI,BETHESDA,MD, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD NOV PY 1994 VL 11 SU 3 BP S15 EP S17 DI 10.1016/0169-5002(94)91860-0 PG 3 WC Oncology; Respiratory System SC Oncology; Respiratory System GA QE251 UT WOS:A1994QE25100005 PM 7704507 ER PT J AU IHDE, DC AF IHDE, DC TI IS THERE A PLACE FOR CLASSICAL ADJUVANT TREATMENT SO LUNG CANCER LA English DT Article; Proceedings Paper CT 3rd IASLC Workshop on Therapy of Non-Small Cell Lung Cancer - Controversies in Staging and Treatment of Locally Advanced Non-Small Cell Lung Cancers CY AUG 29-SEP 02, 1993 CL BRUGGE, BELGIUM SP INT ASSOC STUDY LUNG CANC ID CELL LUNG-CANCER; BRONCHOGENIC-CARCINOMA; RADIATION-THERAPY; STAGE-II; CHEMOTHERAPY; RESECTION; SURVIVAL; IRRADIATION; TRIAL RP IHDE, DC (reprint author), NCI,BLDG 31,ROOM 11A48,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 23 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD NOV PY 1994 VL 11 SU 3 BP S111 EP S116 DI 10.1016/0169-5002(94)91871-6 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA QE251 UT WOS:A1994QE25100016 PM 7704503 ER PT J AU VADASZ, C SZIRAKI, I MURTHY, LR SASVARISZEKELY, M KABAI, P LASZLOVSZKY, I FLEISCHER, A JUHASZ, B ZAHORCHAK, R AF VADASZ, C SZIRAKI, I MURTHY, LR SASVARISZEKELY, M KABAI, P LASZLOVSZKY, I FLEISCHER, A JUHASZ, B ZAHORCHAK, R TI TRANSFER OF BRAIN DOPAMINE SYSTEM-SPECIFIC QUANTITATIVE TRAIT LOCI ONTO A C57BL/6BYJ BACKGROUND SO MAMMALIAN GENOME LA English DT Note ID GENETIC-ANALYSIS; MOTOR-ACTIVITY; MOUSE; STRIATUM; NEURONS; STRAINS; NUMBER; MICE; MAP C1 NYU,MED CTR,DEPT PSYCHIAT,NEW YORK,NY 10016. RES GENET INC,HUNTSVILLE,AL 35801. NIMH,CLIN SCI LAB,NEUROTOXICOL & NEUROPROTECT UNIT,BETHESDA,MD 20892. CUNY MT SINAI SCH MED,DEPT PSYCHIAT,NEW YORK,NY 10029. SEMMELWEIS UNIV MED,SCH MED,INST BIOCHEM 1,H-1088 BUDAPEST,HUNGARY. MENNINGER CLIN,RES DEPT,TOPEKA,KS 66601. GEDEON RICHTER CHEM WORKS LTD,CHEM WORKS,PHARMACOL RES CTR,H-1475 BUDAPEST,HUNGARY. ENERGOTECHNO,H-1024 BUDAPEST,HUNGARY. RP VADASZ, C (reprint author), NATHAN S KLINE INST PSYCHIAT RES,NEUROBEHAV GENET LAB,140 OLD ORANGEBURG RD,ORANGEBURG,NY 10962, USA. FU NCRR NIH HHS [1 P41 RR03655]; NINDS NIH HHS [NS 19788] NR 14 TC 14 Z9 14 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD NOV PY 1994 VL 5 IS 11 BP 735 EP 737 DI 10.1007/BF00426084 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA PP615 UT WOS:A1994PP61500014 PM 7873887 ER PT J AU LEE, CGL GILBERT, DJ OBRIEN, WE JENKINS, NA COPELAND, NG AF LEE, CGL GILBERT, DJ OBRIEN, WE JENKINS, NA COPELAND, NG TI LOCALIZATION OF A NOVEL, LPS-INDUCIBLE MEMBER OF THE THYMIDYLATE KINASE FAMILY TO MOUSE CHROMOSOME-12 SO MAMMALIAN GENOME LA English DT Note ID MACROPHAGES; EXPRESSION C1 BAYLOR COLL MED,DEPT MOLEC & HUMAN GENET,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT BIOCHEM,HOUSTON,TX 77030. NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. NR 8 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD NOV PY 1994 VL 5 IS 11 BP 742 EP 743 DI 10.1007/BF00426089 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA PP615 UT WOS:A1994PP61500019 PM 7873892 ER PT J AU BROSSI, A AF BROSSI, A TI CHIRAL DRUGS - SYNOPSIS SO MEDICINAL RESEARCH REVIEWS LA English DT Article ID ASYMMETRIC-SYNTHESIS; ABSOLUTE-CONFIGURATION; EXPEDIENT SYNTHESIS; AMINES; ALCOHOLS; DERIVATIVES; BINDING; TUBULIN; POTENT; PURITY C1 NIH,BETHESDA,MD 20892. RP BROSSI, A (reprint author), GEORGETOWN UNIV,DEPT CHEM,WASHINGTON,DC 20057, USA. NR 48 TC 14 Z9 15 U1 1 U2 3 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0198-6325 J9 MED RES REV JI Med. Res. Rev. PD NOV PY 1994 VL 14 IS 6 BP 665 EP 691 DI 10.1002/med.2610140604 PG 27 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QF981 UT WOS:A1994QF98100003 PM 7830418 ER PT J AU DENGEL, DR HAGBERG, JM COON, PJ DRINKWATER, DT GOLDBERG, AP AF DENGEL, DR HAGBERG, JM COON, PJ DRINKWATER, DT GOLDBERG, AP TI COMPARABLE EFFECTS OF DIET AND EXERCISE ON BODY-COMPOSITION AND LIPOPROTEINS IN OLDER MEN SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE BODY FAT DISTRIBUTION; CIRCUMFERENCES; SKINFOLDS; WEIGHT LOSS ID HIGH-DENSITY LIPOPROTEINS; PLASMA-LIPOPROTEINS; FAT DISTRIBUTION; PRECIPITATION PROCEDURE; CARDIOVASCULAR-DISEASE; COMPUTED-TOMOGRAPHY; WEIGHT-LOSS; QUANTITATION; OVERWEIGHT; WOMEN AB Changes in body composition, fat distribution and lipoprotein lipids in response to weight loss elicited by a 10-month program of hypocaloric diet (HD) therapy alone or combined with aerobic exercise training (AEX+HD) were examined in sedentary obese older males. Body composition was assessed by hydrodensitometry and fat distribution was evaluated with skinfold thickness and circumference measures. The HD group underwent a dietary/behavioral modification program to reduce caloric intake. The AEX+HD group underwent a similar dietary modification program combined with aerobic exercise training. Following completion of the study, 15 subjects from each group were individually pair matched based on age (57.1 +/- 1.7 vs 61.3 +/- 2.4 yrs) and their reduction in body mass (-7.6 +/- 1.3 vs -8.0 +/- 1.1 kg). Reductions in fat and fat-free mass and skinfold thickness and circumferences were similar in both groups. In both the AEX+HD and HD groups there were significant reductions in the ratio of low-density lipoproteins to high-density lipoproteins (HDL-C) and triglycerides and a significant increase in HDL(2)-C. There were no differences in final values or absolute and relative changes in the various lipoprotein Values between the two groups. These results suggest weight loss induced by diet alone or combined with aerobic exercise cause similar changes in body composition and lipoprotein lipids. C1 UNIV MARYLAND,SCH MED,DIV GERONTOL,BALTIMORE,MD 21201. UNIV MARYLAND,CTR AGING,COLLEGE PK,MD 20742. NIA,GERONTOL RES CTR,CLIN PHYSIOL LAB,METAB SECT,BALTIMORE,MD 21224. RP DENGEL, DR (reprint author), VET ADM MED CTR,GERIATR SERV,10 N GREENE ST,BALTIMORE,MD 21201, USA. FU NCRR NIH HHS [MO1 RR02719]; NIA NIH HHS [F32 AG-05555, P01 AG-04402] NR 35 TC 24 Z9 24 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD NOV PY 1994 VL 26 IS 11 BP 1307 EP 1315 PG 9 WC Sport Sciences SC Sport Sciences GA PQ033 UT WOS:A1994PQ03300003 PM 7837950 ER PT J AU VADHEIM, KL SINGH, Y KEITH, JM AF VADHEIM, KL SINGH, Y KEITH, JM TI EXPRESSION AND MUTAGENESIS OF RECOMBINANT CHOLERA-TOXIN-A SUBUNIT SO MICROBIAL PATHOGENESIS LA English DT Article DE CHOLERA TOXIN; PCR MUTAGENESIS; ADP-RIBOSYLATION; KDEL; RECOMBINANT CT-A ID ADP-RIBOSYLTRANSFERASE ACTIVITY; PERTUSSIS TOXIN; NUCLEOTIDE-SEQUENCE; PSEUDOMONAS EXOTOXIN; ENZYME-ACTIVITY; S-1 SUBUNIT; A-SUBUNIT; GENES; ENTEROTOXIN; S1-SUBUNIT AB ADP-ribosylating protein exotoxins from Vibrio cholerae (CT) and Escherichia coli (LT-I) share two short regions of sequence similarity with Bordetella pertussis toxin (PT). Previous studies have indicated that substitution of arginine for lysine 7 within the first region of CT drastically decreases ADP ribosyltransferase activity. We have more closely defined the role of other amino acids in this region by generating modified proteins in which arginine 7 was replaced with lysine (R7K), aspartate 9 was replaced with arginine (D9R), glycine was substituted for proline 12 (P12G), amino acids 6 to 13 were deleted (Delta 613) or the C-terminal KDEL sequence was changed to NEDL. The modified proteins R7K, D9R and Delta 613 exhibited undetectable ADP ribosyltransferase activity. Comparison of the tryptic digest of R7K with native CT suggested that changes in protein conformation may be responsible for the loss of ADP-ribosylation activity. C1 NIDR, MICROBIAL ECOL LAB, BETHESDA, MD 20892 USA. NR 23 TC 6 Z9 6 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0882-4010 J9 MICROB PATHOGENESIS JI Microb. Pathog. PD NOV PY 1994 VL 17 IS 5 BP 339 EP 346 DI 10.1006/mpat.1994.1079 PG 8 WC Immunology; Microbiology SC Immunology; Microbiology GA QE202 UT WOS:A1994QE20200006 PM 7723660 ER PT J AU POLICASTRO, PF HACKSTADT, T AF POLICASTRO, PF HACKSTADT, T TI DIFFERENTIAL ACTIVITY OF RICKETTSIA-RICKETTSII OMPA AND OMPS PROMOTER REGIONS IN A HETEROLOGOUS REPORTER GENE SYSTEM SO MICROBIOLOGY-SGM LA English DT Article DE RICKETTSIA RIKETTSII; ALPHA-PROTEOBACTERIA; OUTER MEMBRANE PROTEINS; PROMOTER; TRANSCRIPTION ID OUTER-MEMBRANE PROTEIN; MESSENGER-RNA STABILIZER; ESCHERICHIA-COLI; PROWAZEKII; EXPRESSION; ANTIGEN; SURFACE; IDENTIFICATION; SEQUENCES; CLEAVAGE AB The outer membrane of the Gram-negative obligate intracellular parasite Rickettsia rickettsii contains two large surface protein antigens with approximate molecular masses of 200 and 135 kDa termed rOmpA and rOmpB, respectively. rOmpB is the most abundant protein in the outer membrane, while rOmpA is a relatively minor constituent. Densitometry of intrinsically radiolabelled protein profiles from R. rickettsii-infected Veto cells indicated a molar ratio of approximately 1:9 between rOmpA and rOmpB. The putative promoter-5' untranslated regions (5' UTR) from their recently characterized genes (rompA and rompB) were placed in the promoter assay vector pKK232-8 to test whether these elements conserve aspects of differential expression in a heterologous host-reporter system. Primer extension analysis of RNA from Escherichia coli clones containing the constructs indicated that E. coli RNA polymerase faithfully utilizes rompA and rompB transcription start sites identified previously in R. rickettsii. The rompB insert directs 28-fold higher levels of chloramphenicol acetyl transferase activity than the rompA insert. RP POLICASTRO, PF (reprint author), NIAID, ROCKY MT LABS, INTRACELLULAR PARASITES LAB, HAMILTON, MT 59840 USA. NR 39 TC 11 Z9 11 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD NOV PY 1994 VL 140 BP 2941 EP 2949 PN 11 PG 9 WC Microbiology SC Microbiology GA PU228 UT WOS:A1994PU22800003 PM 7812435 ER PT J AU HAYES, HM TARONE, RE CASEY, HW JENNINGS, PB HILDEBRANDT, PK REARDON, MJ AF HAYES, HM TARONE, RE CASEY, HW JENNINGS, PB HILDEBRANDT, PK REARDON, MJ TI US MILITARY WORKING DOGS WITH VIETNAM SERVICE - DEFINITION AND CHARACTERISTICS OF THE COHORT SO MILITARY MEDICINE LA English DT Article AB We verified and corrected inaccuracies in descriptive profile information on military working dogs (MWDs) that died from 1965 to 1980 and were reported in the Armed Forces Institute of Pathology Registry of Veterinary Pathology. Using other available military records, we determined which dogs served in Vietnam, Identified were 3,895 MWDs with a unique identity tattoo that served in Vietnam, of which 2,389 served exclusively with U.S. military forces and died in Vietnam, Another 479 Vietnam veteran MWDs completed their service elsewhere, This overall effort resulted in signalment corrections, generally age at death, in 21% of the Registry MWD accessions during the study period, The improved definition and characterization of the Vietnam cohort will lead to greater precision in epidemiologic investigations of the health effects from the Vietnam experience in U.S. military working dogs. RP HAYES, HM (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 1 U2 4 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0026-4075 J9 MIL MED JI Milit. Med. PD NOV PY 1994 VL 159 IS 11 BP 669 EP 675 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA QD553 UT WOS:A1994QD55300004 PM 7885593 ER PT J AU VANDIJK, MR MCCONKEY, GA VINKENOOG, R WATERS, AP JANSE, CJ AF VANDIJK, MR MCCONKEY, GA VINKENOOG, R WATERS, AP JANSE, CJ TI MECHANISMS OF PYRIMETHAMINE RESISTANCE IN 2 DIFFERENT STRAINS OF PLASMODIUM-BERGHEI SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Note DE PLASMODIUM BERGHEI; MALARIA; DIHYDROFOLATE REDUCTASE THYMIDYLATE SYNTHASE; ANTIFOLATE; DRUG RESISTANCE; TRANSFECTION ID DIHYDROFOLATE-REDUCTASE; FALCIPARUM; MALARIA; GENE; CYCLOGUANIL; MUTATIONS; SELECTION; CHABAUDI C1 NIAID,MALARIA RES LAB,BETHESDA,MD 20892. RP VANDIJK, MR (reprint author), LEIDEN UNIV,PARASITOL LAB,WASSENAARSEWEG 62,POB 9605,2300 RC LEIDEN,NETHERLANDS. RI Waters, Andy/C-9377-2009 OI Waters, Andy/0000-0001-8900-2982 NR 18 TC 29 Z9 30 U1 0 U2 3 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 NOV PY 1994 VL 68 IS 1 BP 167 EP 171 DI 10.1016/0166-6851(94)00163-4 PG 5 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA PT678 UT WOS:A1994PT67800017 PM 7891743 ER PT J AU KIM, YW OTTERSON, GA KRATZKE, RA COXON, AB KAYE, FJ AF KIM, YW OTTERSON, GA KRATZKE, RA COXON, AB KAYE, FJ TI DIFFERENTIAL SPECIFICITY FOR BINDING OF RETINOBLASTOMA BINDING-PROTEIN-2 TO RB, P107, AND TATA-BINDING PROTEIN SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID LARGE T-ANTIGEN; VIRUS-40 LARGE-T; GENE-PRODUCT; TRANSCRIPTION FACTOR; ADENOVIRUS E1A; SUSCEPTIBILITY GENE; CELLULAR PROTEINS; CYCLIN-A; VIRAL ONCOPROTEINS; C-MYC AB The growth suppressor activities of the RB and p107 products are believed to be mediated by the reversible binding of a heterogeneous family of cellular proteins to a conserved T/E1A pocket domain that is present within both proteins. To study the functional role of these interactions, we examined the properties of cellular retinoblastoma binding protein 2 (RBP2) binding to RB, p107, and the related TATA-binding protein (TBP) product. We observed that although RBP2 bound exclusively to the T/E1A pocket of p107, it could interact with RB through independent T/E1A and non-T/E1A domains and with TBP only through the non-T/E1A domain. Consistent with this observation, we found that a mutation within the Leu-X-Cys-X-Glu motif of RBP2 resulted in loss of ability to precipitate p107, while RB- and TBP-binding activities were retained. We located the non-T/E1A binding site of RBP2 on a 15-kDa fragment that is independent from the Leu-X-Cys-X-Glu motif and encodes binding activity for RB and TBP but does not interact with p107. Despite the presence of a non-T/E1A binding site, however, recombinant RBP2 retained the ability to preferentially precipitate active hypophosphorylated RB from whole-cell lysates. In addition, we found that cotransfection of RBP2, can reverse in vivo RB-mediated suppression of E2F activity. These findings confirm the differential binding specificities of the related RB, p107, and TBP proteins and support the presence of multifunctional domains on the nuclear RBP2 product which may allow complex interactions with the cellular transcription machinery. C1 USN HOSP,NCI NAVY MED ONCOL BRANCH,BETHESDA,MD 20889. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20889. RI kaye, frederic/E-2437-2011 NR 59 TC 39 Z9 42 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 NOV PY 1994 VL 14 IS 11 BP 7256 EP 7264 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PM684 UT WOS:A1994PM68400024 PM 7935440 ER PT J AU CVEKL, A SAX, CM BRESNICK, EH PIATIGORSKY, J AF CVEKL, A SAX, CM BRESNICK, EH PIATIGORSKY, J TI A COMPLEX ARRAY OF POSITIVE AND NEGATIVE ELEMENTS REGULATES THE CHICKEN ALPHA-A-CRYSTALLIN GENE - INVOLVEMENT OF PAX-6, USF, CREB AND/OR CREM, AND AP-1 PROTEINS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TISSUE-SPECIFIC EXPRESSION; TRANSCRIPTION FACTOR USF; HOMEOBOX-CONTAINING GENE; LENS EPITHELIAL-CELLS; RESPONSE ELEMENT; ENHANCER ELEMENT; BINDING-PROTEINS; TRANSGENIC MICE; TATA BOX; MOUSE AB The abundance of crystallins (>80% of the soluble protein) in the ocular lens provides advantageous markers for selective gene expression during cellular differentiation. Here we shown by functional and protein-DNA binding experiments that the chicken alpha A-crystallin gene is regulated by at least five control elements located at sites A (-148 to -139), B (-138 to -132), C (-128 to -101), D (-102 to -93), and E (-56 to -41). Factors interacting with these sites were characterized immunologically and by gel mobility shift experiments. The results are interpreted with the following model. Site A binds USF and is part of a composite element with site B. Site B binds CREB and/or CREM to enhance expression in the lens and binds an AP-1 complex including CREB, Fra2 and/or JunD which interacts with USF on site A to repress expression in fibroblasts. Sites C and E (which is conserved across species) bind Pax-6 in the lens to stimulate alpha A-crystallin promoter activity. These experiments provide the first direct data that Pax-6 contributes to the lens-specific expression of a crystallin gene. Site D (-104 to -93) binds USF and is a negative element. Thus, the data indicate that USF, CREB and/or CREM (or AP-1 factors), and Pax-6 bind a complex array of positive and negative cis-acting elements of the chicken alpha A-crystallin gene to control high expression in the lens and repression in fibroblasts. C1 NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892. NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. RI Cvekl, Ales/B-2427-2013 NR 73 TC 116 Z9 116 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1994 VL 14 IS 11 BP 7363 EP 7376 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PM684 UT WOS:A1994PM68400035 PM 7935450 ER PT J AU VANDERGON, TL REITMAN, M AF VANDERGON, TL REITMAN, M TI EVOLUTION OF CHICKEN REPEAT-1 (CR-1) ELEMENTS - EVIDENCE FOR ANCIENT SUBFAMILIES AND MULTIPLE PROGENITORS SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE NON-LTR RETROTRANSPOSITION; EVOLUTION; REPETITIVE DNA; PHYLOGENETIC ANALYSIS; CHICKEN (GALLUS GALLUS); CR-1 ID REPETITIVE DNA-SEQUENCE; INTERSPERSED REPEATS; HUMAN GENOME; L1 FAMILY; CR-1; ALU; ORGANIZATION; AMPLIFICATION; RETROPOSONS; CONFIDENCE AB Chicken repeat 1 (CR1) is an interspersed repetitive element that is a member of the non-long terminal repeat class of retrotransposons. A data set of chicken 95 CR1 elements was compiled and the phylogeny of the 52 elements with the most complete 3' ends was examined. We interpret the branching pattern as clustering into at least six subfamilies, designated A-F. The presence of highly similar elements within the B, C, D, and F subfamilies is evidence that a distinct progenitor has spawned each of these subfamilies. The nucleotide divergence between members of subfamily C was 5%-8%, suggesting that this subfamily has undergone a relatively recent burst of retrotransposition. The A and E subfamilies may have been spawned from ancestors of these four progenitors or from other, distinct progenitors. The consensus sequences for the six subfamilies showed considerable divergence, implying that the CR1 subfamilies are ancient. The CR1 elements in each subfamily have truncated 5' ends and a 3' end consisting of greater than or equal to 2 repeats of an 8-bp sequence. We estimate that there are approximately 100,000 CR1 elements in the chicken genome. Twelve CR1 sequences from avian species other than chicken were identified. Some of these sequences grouped into different subfamilies, demonstrating that multiple subfamilies existed early in avian evolution. Reptilian CR1 sequences were also identified. demonstrating that the CR1 element arose before the divergence of birds and reptiles. C1 NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. RI Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 NR 48 TC 57 Z9 59 U1 0 U2 0 PU SOC MOLECULAR BIOLOGY EVOLUTION PI LAWRENCE PA PO BOX 1897, LAWRENCE, KS 66044-8897 SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD NOV PY 1994 VL 11 IS 6 BP 886 EP 898 PG 13 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA PQ035 UT WOS:A1994PQ03500007 PM 7815928 ER PT J AU ROSEN, JB KIM, SY POST, RM AF ROSEN, JB KIM, SY POST, RM TI DIFFERENTIAL REGIONAL AND TIME-COURSE INCREASES IN THYROTROPIN-RELEASING-HORMONE, NEUROPEPTIDE-Y AND ENKEPHALIN MESSENGER-RNAS FOLLOWING AN AMYGDALA-KINDLED SEIZURE SO MOLECULAR BRAIN RESEARCH LA English DT Article DE KINDLING; THYROTROPIN-RELEASING HORMONE; ENKEPHALIN; NEUROPEPTIDE Y; IN SITU HYBRIDIZATION; MESSENGER-RNA; NEUROPEPTIDE; AMYGDALA; HIPPOCAMPUS; ENTORHINAL CORTEX; PYRIFORM CORTEX; PERIRHINAL CORTEX ID FOS MESSENGER-RNA; C-FOS; RAT-BRAIN; ENTORHINAL CORTEX; GENE-EXPRESSION; BETA-ENDORPHIN; DENTATE GYRUS; PROENKEPHALIN; HIPPOCAMPUS; IMMUNOREACTIVITY AB Previous studies have shown that neuropeptide mRNA expression is altered in the dentate gyrus, and pyriform, entorhinal and perirhinal cortices following amygdala kindling. However, because rats were kindled every day and some mRNA alterations last longer than 24 h, a true measure of the alterations induced by a single seizure was confounded by the previous day's seizure. To circumvent this problem, rats were fully kindled, had six days without stimulation, and then were given one more seizure. Rats were sacrificed either 4 h, 24 h or 4 days after this last seizure. The levels of mRNAs for TRH, NPY and ENK were measured in the dentate gyrus and limbic cortices. Four hours after a seizure, TRH and NPY mRNAs were maximally increased in the dentate gyrus granule layer, but returned to baseline levels by 24 h. In contrast, 4 h after a seizure, TRH and NPY mRNAs were not, or only slightly, increased in the pyriform, entorhinal and perirhinal cortices, but significantly elevated 24 h after a seizure. ENK mRNA was increased both 4 and 24 h after a seizure in the pyriform, entorhinal and perirhinal cortices but showed no increases in the dentate gyrus at any time. By 4 days, peptide mRNA levels returned to baseline, except for ENK mRNA in the pyriform cortex. These results demonstrate a non-uniform and complex pattern of peptide mRNA expression following an amygdala kindled seizure. They further suggest that regional and time course differences in gene transcription and expression may be important factors in understanding both the transient, adaptive anticonvulsant and longer lasting proconvulsant effects of these neuropeptides. RP ROSEN, JB (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,BETHESDA,MD 20892, USA. NR 52 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD NOV PY 1994 VL 27 IS 1 BP 71 EP 80 DI 10.1016/0169-328X(94)90186-4 PG 10 WC Neurosciences SC Neurosciences & Neurology GA PP143 UT WOS:A1994PP14300009 ER PT J AU KAVETY, B JENKINS, NA FLETCHER, CF COPELAND, NG MORGAN, JI AF KAVETY, B JENKINS, NA FLETCHER, CF COPELAND, NG MORGAN, JI TI GENOMIC STRUCTURE AND MAPPING OF PRECEREBELLIN AND A PRECEREBELLIN-RELATED GENE SO MOLECULAR BRAIN RESEARCH LA English DT Note DE CEREBELLUM; CEREBELLIN; GENE STRUCTURE; NEUROLOGICAL MUTANT; CHROMOSOMAL LOCATION ID LINKAGE MAP; CEREBELLIN; NEUROPEPTIDE; PEPTIDES; PROTEIN; MARKER; BRAIN; CHAIN AB The cerebellum-specific hexadecapeptide, cerebellin, is derived from a larger precursor, precerebellin, that has sequence homology to the complement component C1qB. We report the cloning of the murine homolog of precerebellin, Cbln1, and a closely related gene, Cbln2. Amino acid comparison of Cbln1 with Cbln2 revealed that Cbln2 is 88% identical to the carboxy terminal region of Cbln1. That these are independent genes was confirmed by Southern analysis and genomic mapping. Cbln1 was positioned to the central region of mouse chromosome 8, 2.3 cM distal of JunB and 6.0 cM proximal of Mt1, while Cbln2 mapped to the distal end of mouse chromosome 18, 1.7 cM telomeric of Mbp. C1 ROCHE INST MOLEC BIOL,ROCHE RES CTR,NUTLEY,NJ 07110. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. NR 17 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD NOV PY 1994 VL 27 IS 1 BP 152 EP 156 DI 10.1016/0169-328X(94)90196-1 PG 5 WC Neurosciences SC Neurosciences & Neurology GA PP143 UT WOS:A1994PP14300019 ER PT J AU GOODNIGHT, J MISCHAK, H MUSHINSKI, JF AF GOODNIGHT, J MISCHAK, H MUSHINSKI, JF TI ASSOCIATION OF ELEVATED LEVELS OF PROTEIN-KINASE C-ZETA MESSENGER-RNA AND PROTEIN WITH MURINE B-LYMPHOCYTIC NEOPLASIA SO MOLECULAR CARCINOGENESIS LA English DT Article DE HEMATOPOIETIC; NEOPLASMS; PKC ISOZYMES; PLASMA CELL TUMORS; NORTHERN BLOT; WESTERN BLOT ID EXPRESSION PATTERN; RAT FIBROBLASTS; PHORBOL ESTERS; SIGNAL-TRANSDUCTION; HEMATOPOIETIC-CELLS; GROWTH-CONTROL; FAMILY; ACTIVATION; ISOFORM; NPKC AB Expression of mRNA for protein kinase C (PKC)-alpha, -beta, -gamma, -delta, -epsilon, -zeta, and -eta has been shown, by polymerase chain reaction-generated isozyme-specific probes, to be cell-type- and differentiation-stage-specific in mouse hemopoietic cells. Recently, we cloned a 2.2-kb mouse PKC-zeta cDNA. In this study, we used the nearly full-length cDNA PKC-zeta probe to demonstrate that expression of PKC-zeta was significantly elevated in lymphocytic neoplasms at both the mRNA and protein levels. Normal brain, kidney, and liver contain 2.4- and 4.4-kb mRNAs, whereas normal lymphoid organs (spleen, thymus, and lymph nodes) express barely detectable amounts of PKC-zeta. These vanishingly small levels of PKC-zeta mRNA did not increase when polyclonal spleen B-cell proliferation and differentiation were induced in vivo,with anti-immunoglobulin D antiserum or in vitro with lipopolysaccharide. In contrast, 2.4-kb transcripts of PKC-zeta are abundant in virtually all neoplastic B-lymphocytic cell lines. Furthermore, additional transcripts of a novel size, about 7 and 8 kb, were found in several mature B-cell lymphomas and plasma cell tumors. Western blot analysis of protein extracts from normal B cells and hemopoietic tumors confirmed that these quantitative differences in PKC-zeta mRNA also exist at the protein level. That is, only trace amounts of PKC-zeta protein were detectable in pro-B cells and pre-B cells, but abundant amounts of this isoform were found in protein extracts from most B-cell lymphomas and plasma cell tumors. These findings suggest that this atypical member of the PKC multigene family participates in the multistep process of malignant transformation of lymphocytes. (C) 1994 Wiley-Liss, Inc. C1 NCI, GENET LAB, MOLEC GENET SECT, BETHESDA, MD 20892 USA. RI Mischak, Harald/E-8685-2011 NR 38 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0899-1987 EI 1098-2744 J9 MOL CARCINOGEN JI Mol. Carcinog. PD NOV PY 1994 VL 11 IS 3 BP 131 EP 137 DI 10.1002/mc.2940110303 PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA QG456 UT WOS:A1994QG45600002 PM 7945801 ER PT J AU BROWER, RC ENGLAND, R TAKESHITA, T KOZLOWSKI, S MARGULIES, DH BERZOFSKY, JA DELISI, C AF BROWER, RC ENGLAND, R TAKESHITA, T KOZLOWSKI, S MARGULIES, DH BERZOFSKY, JA DELISI, C TI MINIMAL REQUIREMENTS FOR PEPTIDE MEDIATED ACTIVATION OF CD8(+) CTL SO MOLECULAR IMMUNOLOGY LA English DT Article DE MHC MOLECULES; CLASS I; MATH MODEL; T CELLS ID CLASS-I MHC; T-CELL RECEPTOR; MOLECULES; BINDING; ASSOCIATION; MEMBRANES; COMPLEXES; ANTIGEN AB A physical chemical model of T cell stimulation by class I-peptide complexes was developed and used to analyse in vitro studies of gamma-interferon release as a function of the number of peptide and MHC molecules. The analysis provided reasonable estimates of well identified parameters, including equilibrium constants and the minimum number of T cell receptor-class I-peptide ternary complexes on a presenting cell required to activate T cells. The latter number was estimated as 3-5 per T cell. This is in distinct contrast to estimates in the literature of the number of peptide-MHC complexes required for activity, which is necessarily larger. The analysis also predicted that activity is potentiated by interaction between class I molecules, even if one member of the pair is not bound by antigen. The analytical approach used in this paper may be applicable to other activation systems. C1 BOSTON UNIV,DEPT PHYS,BOSTON,MA 02215. NCI,MOLEC IMMUNOGENET & VACCINE RES SECT,BETHESDA,MD 20892. NIAID,MOLEC BIOL SECT,IMMUNOL LAB,BETHESDA,MD 20892. BOSTON UNIV,DEPT BIOMED ENGN,BOSTON,MA 02215. RP BROWER, RC (reprint author), BOSTON UNIV,DEPT ELECT COMP & SYST ENGN,44 CUMMINGTON ST,BOSTON,MA 02215, USA. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 FU NIAID NIH HHS [AI30535] NR 24 TC 62 Z9 62 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD NOV PY 1994 VL 31 IS 16 BP 1285 EP 1293 DI 10.1016/0161-5890(94)90079-5 PG 9 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA PU071 UT WOS:A1994PU07100009 PM 7969189 ER PT J AU PETEN, EP STRIKER, LJ FOGO, A ICHIKAWA, I PATEL, A STRIKER, GE AF PETEN, EP STRIKER, LJ FOGO, A ICHIKAWA, I PATEL, A STRIKER, GE TI THE MOLECULAR-BASIS OF INCREASED GLOMERULOCLEROSIS AFTER BLOCKADE OF THE RENIN-ANGIOTENSIN SYSTEM IN GROWTH-HORMONE TRANSGENIC MICE SO MOLECULAR MEDICINE LA English DT Article ID NEPHROTIC SYNDROME; GLOMERULAR INJURY; GLOMERULOSCLEROSIS; HYPERTENSION; COLLAGEN; KIDNEY; CELLS; INHIBITION; CAPTOPRIL; FAILURE AB Background: Angiotensin converting enzyme inhibitor (ACEi) therapy delays the onset of renal failure in diabetic nephropathy and inhibits or delays the onset of proteinuria in several animal models. Materials and Methods: We examined this question using a transgenic model of chronic glomerulosclerosis caused by an excess production of growth hormone (GH) in which there is progressive glomerular scarring leading to uremia. In addition, since GH mice do not have systemic hypertension or an elevated glomerular filtration rate, we could address the question of whether ACEi or angiotensin II receptor antagonists (AII RA) had an effect on the development of glomerulosclerosis under these conditions. Since excess matrix accumulates in glomerulosclerosis because of alterations in the balance between its synthesis and degradation, we examined the effect of ACEi and AII RA on these parameters. Results: Systemic blood pressure was unaffected by ACEi treatment, but the glomerular filtration rate decreased 85%. ACEi-treated mice had increased mesangial deposition of type I collagen and decreased 105 kD complex collagenase activity. In addition, ACEi-treated GH mice had increased glomerular alpha 1 type I collagen, alpha 1 type IV collagen, and alpha-smooth muscle cell actin mRNAs. No changes were noted in beta actin, or 72 kD metalloproteinase mRNAs. The result of these changes was a net increase in sclerosis. Surprisingly, GH mice treated with ACEi or AngII RA developed marked renal arteriolar lesions. Conclusions: In some forms of glomerulosclerosis, the lesions develop independently of angiotensin II. Pharmacological inhibition of angiotensin II, in this circumstance, may aggravate the lesions through disregulation of the levels and the balance between glomerular matrix synthesis and degradation. C1 NIDDKD,RENAL CELL BIOL SECT,METAB DIS BRANCH,BETHESDA,MD 20892. VANDERBILT UNIV,SCH MED,DEPT PEDIAT & PATHOL,NASHVILLE,TN. FU NIDDK NIH HHS [DK 44757, DK 37868, DK42131] NR 36 TC 11 Z9 11 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 1076-1551 J9 MOL MED JI Mol. Med. PD NOV PY 1994 VL 1 IS 1 BP 104 EP 115 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA QX598 UT WOS:A1994QX59800012 PM 8790606 ER PT J AU SZALLASI, Z DENNING, MF SMITH, CB DLUGOSZ, AA YUSPA, SH PETTIT, GR BLUMBERG, PM AF SZALLASI, Z DENNING, MF SMITH, CB DLUGOSZ, AA YUSPA, SH PETTIT, GR BLUMBERG, PM TI BRYOSTATIN 1 PROTECTS PROTEIN KINASE-C-DELTA FROM DOWN-REGULATION IN MOUSE KERATINOCYTES IN PARALLEL WITH ITS INHIBITION OF PHORBOL ESTER-INDUCED DIFFERENTIATION SO MOLECULAR PHARMACOLOGY LA English DT Article ID LEUKEMIA-CELLS; 12-MYRISTATE 13-ACETATE; EPIDERMAL-CELLS; RBL-2H3 CELLS; PHASE-I; MODULATION; EXPRESSION; EPSILON; ISOZYMES; ERYTHROLEUKEMIA AB Bryostatin 1 and phorbol-12-myristate-13-acetate (PMA) are both potent activators of protein kinase C (PKC), although in primary mouse keratinocytes bryostatin 1 does not induce differentiation and blocks PMA-induced differentiation. We report here that in primary mouse keratinocytes PMA caused translocation of PKC-epsilon to the Triton X-100-soluble fraction with an approximately 2-order of magnitude higher potency, compared with translocation of PKC-alpha and PKC-delta. The kinetics of translocation were fastest for PKC-epsilon, slower for PKC-alpha, and slowest for PKC-delta. At 5-20 min bryostatin 1 showed potency similar to that of PMA for translocating PKC-alpha, higher potency for translocating PKC-delta, and lower potency for translocating PKC-epsilon. At a later time (6 hr), bryostatin 1 was 1-2 orders magnitude more potent than PMA for causing loss of PKC-alpha, -delta, and -epsilon from the soluble fraction. Bryostatin 1 was 40-fold more potent than PMA for down-regulating PKC-alpha and showed a biphasic dose-response curve for down-regulating PKC-delta. Bryostatin 1 at 0.1-1 nM down-regulated PKC-delta to a similar extent as did PMA. Bryostatin 1 at 100 nM to 1 mu M, on the other hand, failed to induce down-regulation, and these high (100 nM to 1 mu M) doses of bryostatin 1 showed noncompetitive inhibition of PKC-delta down-regulation by 1 mu M PMA after coapplication. This protected portion of PKC-delta retained kinase activity. The dose-response curve for bryostatin 1 protection of PKC-delta from down-regulation by PMA correlated with bryostatin 1 inhibition of the effects of PMA on cornified envelope formation (a marker of differentiation) and epidermal growth factor binding. Although PKC-epsilon was readily translocated by both PMA and bryostatin 1, the PKC-epsilon originally associated with the particulate fraction showed no down-regulation by either of these agents. We hypothesize that differential regulation of PKC isozymes by PMA and bryostatin 1 may contribute to the different patterns of biological responses that they induce. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. ARIZONA STATE UNIV,CANC RES INST,TEMPE,AZ 85287. ARIZONA STATE UNIV,DEPT CHEM,TEMPE,AZ 85287. NR 43 TC 113 Z9 113 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 NOV PY 1994 VL 46 IS 5 BP 840 EP 850 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PV326 UT WOS:A1994PV32600007 PM 7969070 ER PT J AU AHLUWALIA, GS COONEY, DA SHIRASAKA, T MITSUYA, H DRISCOLL, JS JOHNS, DG AF AHLUWALIA, GS COONEY, DA SHIRASAKA, T MITSUYA, H DRISCOLL, JS JOHNS, DG TI ENHANCEMENT BY 2'-DEOXYCOFORMYCIN OF THE 5'-PHOSPHORYLATION AND ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS ACTIVITY OF 2',3'-DIDEOXYADENOSINE AND 2'-BETA-FLUORO-2',3'-DIDEOXYADENOSINE SO MOLECULAR PHARMACOLOGY LA English DT Article ID ANTIRETROVIRAL AGENT 2',3'-DIDEOXYADENOSINE; IMP DEHYDROGENASE STIMULATE; HUMAN LYMPHOID-CELLS; CELLULAR PHARMACOLOGY; 2',3'-DIDEOXYINOSINE; PHOSPHORYLATION; INFECTIVITY; RIBAVIRIN; HIV; 2',3'-DIDEOXYNUCLEOSIDES AB The anti-human immunodeficiency virus agents 2',3'-dideoxyadenosine (ddAdo) and 2'-beta-fluoro-2',3'-dideoxyadenosine (2'-beta-F-ddAdo) are rapidly converted, both in vitro and in vivo, to the corresponding inosine analogs by the widely distributed enzyme adenosine deaminase (EC 3.5.4.4). We have determined the effects of the potent adenosine deaminase inhibitor 2'-deoxy-coformycin (2'-dCF) on ddAdo and 2'-beta-F-ddAdo metabolism in MOLT-4 cells and on ddAdo antiviral activity in the ATH8 test system. At levers as low as 5 nM in the incubation medium, 2'-dCF effectively blocks the extracellular deamination of both agents, thus permitting their rapid cellular uptake as the unchanged parent compounds, rather than as the less lipid-soluble 2',3'-dideoxyinosine or 2'-beta-fluoro-2',3'-dideoxyinosine. The result is a significant increase in intracellular levels of the pharmacologically active forms 2',3' -dideoxyadenosine-5'-triphosphate and 2'-beta-fluoro-2',3'-dideoxyadenosine-5'-triphosphate. The effect becomes maximal over the range of 50-250 nM 2'-dCF and declines to control levels when extracellular 2'-dCF revels exceed 1 mu M. This decrease in ddAdo and 2'-beta-F-ddAdo phosphorylation with higher levels of the inhibitor appears to result from intracellular penetration of 2'-dCF and consequent inhibition of intracellular deamination, a critical step in the activation of both agents through the 5'-nucleotidase pathway. In anti-human immunodeficiency virus assays, a 2.2-fold increase in ddAdo antiviral potency was seen at 2'-dCF levels of 20 and 50 nM. C1 NCI,MED CHEM LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NCI,MED BRANCH,EXPTL RETROVIROL SECT,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,BETHESDA,MD 20892. NR 22 TC 5 Z9 5 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 1994 VL 46 IS 5 BP 1002 EP 1008 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PV326 UT WOS:A1994PV32600029 PM 7969062 ER PT J AU RALL, DP AF RALL, DP TI SHOE-LEATHER EPIDEMIOLOGY - THE FOOTPADS OF MICE AND RATS - ANIMAL TESTS IN ASSESSMENT OF OCCUPATIONAL RISKS SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Article ID CARCINOGENICITY; TOXICITY RP RALL, DP (reprint author), NATL INST ENVIRONM HLTH SCI,5302 RENO RD NW,WASHINGTON,DC 20015, USA. NR 20 TC 5 Z9 5 U1 0 U2 0 PU MOUNT SINAI HOSPITAL PI NEW YORK PA BOX 1094 ONE GUSTAVE L LEVY PLACE ATTN: CIRCULATION ASST, NEW YORK, NY 10029-6574 SN 0027-2507 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD NOV PY 1994 VL 61 IS 6 BP 504 EP 508 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA PZ229 UT WOS:A1994PZ22900009 PM 7838166 ER PT J AU DEUSCHL, G TORO, C HALLETT, M AF DEUSCHL, G TORO, C HALLETT, M TI SYMPTOMATIC AND ESSENTIAL PALATAL TREMOR .2. DIFFERENCES OF PALATAL MOVEMENTS SO MOVEMENT DISORDERS LA English DT Note DE PALATAL TREMOR; PALATAL MOVEMENTS ID MYOCLONUS AB Palatal tremor, a rhythmic movement disorder of the soft palate, may be described as two separate entities: symptomatic palatal tremor (SPT) and essential palatal tremor (EPT). The symptomatic form is associated with brain stem or cerebellar disease, whereas the essential form has no known etiology. A cardinal symptom of EPT is the presence of ear clicks, which do not occur in SPT. Visual observation of the movements in the two disorders suggests that the difference in symptoms is due to the activation of different palatal muscles, the levator veli palatini in SPT and the tenser veli palatini in EPT. Electromyographic recording from the levator veli palatini muscle showed abnormal bursting activity time locked to the palatal movements in patients with SPT, but not in those with EPT. Because the two palatal muscles are innervated by different cranial nerves, SPT and EPT are likely to have separate origins. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BETHESDA,MD 20892. RI Deuschl, Gunther/A-7986-2010 NR 10 TC 34 Z9 34 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD NOV PY 1994 VL 9 IS 6 BP 676 EP 678 DI 10.1002/mds.870090615 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA PP781 UT WOS:A1994PP78100014 PM 7845410 ER PT J AU KAPLAN, NL LEWIS, PO WEIR, BS AF KAPLAN, NL LEWIS, PO WEIR, BS TI AGE OF THE DELTA-F508 CYSTIC-FIBROSIS MUTATION SO NATURE GENETICS LA English DT Letter C1 N CAROLINA STATE UNIV,DEPT STAT,PROGRAM STAT GENET,RALEIGH,NC 27695. RP KAPLAN, NL (reprint author), NIEHS,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 20 Z9 22 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 NOV PY 1994 VL 8 IS 3 BP 216 EP 216 DI 10.1038/ng1194-216a PG 1 WC Genetics & Heredity SC Genetics & Heredity GA PP765 UT WOS:A1994PP76500006 PM 7533028 ER PT J AU HOCHGESCHWENDER, U BRENNAN, MB AF HOCHGESCHWENDER, U BRENNAN, MB TI REDUNDANT GENES SO NATURE GENETICS LA English DT Letter RP HOCHGESCHWENDER, U (reprint author), NIMH,49-B1EE16,BETHESDA,MD 20892, USA. NR 8 TC 3 Z9 3 U1 0 U2 0 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 NOV PY 1994 VL 8 IS 3 BP 219 EP 220 DI 10.1038/ng1194-219 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA PP765 UT WOS:A1994PP76500009 PM 7874162 ER PT J AU STEINGRIMSSON, E MOORE, KJ LAMOREUX, ML FERREDAMARE, AR BURLEY, SK ZIMRING, DCS SKOW, LC HODGKINSON, CA ARNHEITER, H COPELAND, NG JENKINS, NA AF STEINGRIMSSON, E MOORE, KJ LAMOREUX, ML FERREDAMARE, AR BURLEY, SK ZIMRING, DCS SKOW, LC HODGKINSON, CA ARNHEITER, H COPELAND, NG JENKINS, NA TI MOLECULAR-BASIS OF MOUSE MICROPHTHALMIA (MI) MUTATIONS HELPS EXPLAIN THEIR DEVELOPMENTAL AND PHENOTYPIC CONSEQUENCES SO NATURE GENETICS LA English DT Article ID LOOP-HELIX PROTEIN; DNA-BINDING; INSERTIONAL MUTATION; ZIPPER PROTEIN; TRANSCRIPTION; CELLS; LOCUS; GENE; MYC; MAX AB Mutations in the mouse microphthalmia (mi) gene affect the development of a number of cell types including melanocytes, osteoclasts and mast cells. Recently, mutations in the human mi gene (MITF) were found in patients with Waardenburg Syndrome type 2 (WS2), a dominantly inherited syndrome associated with hearing loss and pigmentary disturbances. We have characterized the molecular defects associated with eight murine mi mutations, which vary in both their mode of inheritance and in the cell types they affect. These molecular data, combined with the extensive body of genetic data accumulated for murine mi, shed light on the phenotypic and developmental consequences of mi mutations and offer a mouse model for WS2. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. TEXAS A&M UNIV,COLL VET MED,DEPT VET PATHOBIOL,COLLEGE STN,TX 77843. ROCKEFELLER UNIV,HOWARD HUGHES MED INST,MOLEC BIOPHYS LABS,NEW YORK,NY 10021. TEXAS A&M UNIV,COLL VET MED,DEPT VET ANAT & PUBL HLTH,COLLEGE STN,TX 77843. NINCDS,VIRAL & MOLEC PATHOGENESIS LAB,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CM-37536, N01-CO-4600] NR 57 TC 369 Z9 376 U1 1 U2 13 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 NOV PY 1994 VL 8 IS 3 BP 256 EP 263 DI 10.1038/ng1194-256 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA PP765 UT WOS:A1994PP76500015 PM 7874168 ER PT J AU JOHNSON, GS BASARICKEYS, J GHANBARI, HA LEBOVICS, RS LESCH, KP MERRIL, CR SUNDERLAND, T WOLOZIN, B AF JOHNSON, GS BASARICKEYS, J GHANBARI, HA LEBOVICS, RS LESCH, KP MERRIL, CR SUNDERLAND, T WOLOZIN, B TI PROTEIN ALTERATIONS IN OLFACTORY NEUROBLASTS FROM ALZHEIMER DONORS SO NEUROBIOLOGY OF AGING LA English DT Article DE ALZHEIMERS DISEASE; OLFACTORY NEUROBLAST; DIAGNOSTIC; PROTEIN; 2D ELECTROPHORESIS ID AMYLOID PRECURSOR PROTEIN; DISEASE; PHOSPHORYLATION; EPITHELIUM; BINDING; STATE; TAU AB Definitive diagnosis of Alzheimer's disease (AD) is made by pathologic examination of postmortem brain tissue in conjunction with a clinical history of dementia. To date, there are no good biological markers for a positive diagnosis of AD in the living patient. In an effort to identify biological markers useful both in the clinical and pathologic diagnosis of AD, we have investigated disease specific protein alterations in cultured olfactory neurons. Olfactory neurons are readily accessible by biopsy, can be propagated in primary cell culture as olfactory neuroblasts (ONs), and exhibit several elements of AD brain pathophysiology making them powerful tools for the study of AD. Two-dimensional gel analysis of ON proteins from neuropsychologically evaluated AD donors revealed a set of five proteins (Mr 17-50 kD, pi 4.8-6.7) that were significantly altered in concentration when compared to cells from age-matched controls. Further characterization and microsequence analysis could lead to the identification of proteins that may have important diagnostic or therapeutic value in the treatment of AD. C1 ST ELIZABETH HOSP,NIMH,BIOCHEM GENET LAB,WASHINGTON,DC 20032. NIMH,GERIATR PSYCHIAT SECT,BETHESDA,MD 20892. UNIV WURZBURG,DEPT PSYCHIAT,W-8700 WURZBURG,GERMANY. RP JOHNSON, GS (reprint author), MOLEC GERIATR CORP,101 WAUKEGAN RD,SUITE 970,LAKE BLUFF,IL 60044, USA. RI Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 22 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD NOV-DEC PY 1994 VL 15 IS 6 BP 675 EP 680 DI 10.1016/0197-4580(94)90048-5 PG 6 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA PR280 UT WOS:A1994PR28000002 PM 7891821 ER PT J AU RAPOPORT, SI AF RAPOPORT, SI TI AGING AND THE BLOOD-BRAIN-BARRIER SO NEUROBIOLOGY OF AGING LA English DT Editorial Material ID GLUCOSE TRANSPORTER; PERMEABILITY; RATS RP RAPOPORT, SI (reprint author), NIA,NEUROSCI LAB,BLDG 10,BETHESDA,MD 20892, USA. NR 23 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD NOV-DEC PY 1994 VL 15 IS 6 BP 759 EP 760 DI 10.1016/0197-4580(94)90060-4 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA PR280 UT WOS:A1994PR28000014 PM 7891833 ER PT J AU BERNARDINI, R CHIARENZA, A KAMILARIS, TC RENAUD, N LEMPEREUR, L DEMITRACK, M GOLD, PW CHROUSOS, GP AF BERNARDINI, R CHIARENZA, A KAMILARIS, TC RENAUD, N LEMPEREUR, L DEMITRACK, M GOLD, PW CHROUSOS, GP TI IN-VIVO AND IN-VITRO EFFECTS OF ARGININE-VASOPRESSIN RECEPTOR ANTAGONISTS ON THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS IN THE RAT SO NEUROENDOCRINOLOGY LA English DT Article DE CRH SECRETION; ACTH RELEASE; AVP RECEPTOR ANTAGONISTS; HPA AXIS; VASOPRESSIN ANTAGONISTS; CORTICOTROPIN-RELEASING HORMONE ID CORTICOTROPIN-RELEASING HORMONE; HYPOPHYSIAL-PORTAL CIRCULATION; SECRETION INVITRO; ADRENOCORTICOTROPIN SECRETION; ACTIVATION; AGONISTS; FEEDBACK; NEURONS AB Arginine-vasopressin (AVP) is regarded as a potent stimulator of pituitary adrenocorticotropin (ACTH) secretion and participates therefore in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis function in concert with the physiological activator of the axis, hypothalamic corticotropin-releasing hormone (CRH). We examined the effects of AVP and/or three synthetic V-1b receptor antagonists on the activity of the HPA axis in vivo and in vitro in the rat. AVP was injected intravenously to Sprague-Dawley rats (1 mu g/rat) through an indwelling jugular catheter. AVP stimulated ACTH release, with maximal effect 10 min after injection. Intravenous injection of three V-1b antagonists, [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),2-O-ethyltryrosine,4-valine] arginine vasopressin (d(CH2)(5)[Tyr(Et(2))]VAVP (WK 1- 1), 9-desglycine[1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid),2-O-ethyltyrosine,4-valine] arginine vasopressin desGly(9)d(CH2)(5)[Tyr(Et(2))]-VAVP (WK 3-6), and 9-desglycine[1-(beta-mercapto-beta,beta-cyclopentamethylenpropionic acid),2-D-(O-ethyl)tyrosine,4-valine] arginine vasopressin des Gly(9)d(CH2)(5)[D-Tyr(Et(2))]VAVP (AO 3-21), prevented AVP-stimulated ACTH secretion. Explanted rat hypothalami incubated in vitro with graded concentrations of AVP (10(-14)-10(-5) M) secreted immunoreactive CRH (iCRH) in a concentration-dependent fashion. Maximal stimulatory effect occurred at the concentration of 10(-6) M. Incubation of hypothalami with WK 1- 1, WK 3-6, or AO 3-21 (10(-6) M) prevented AVP-stimulated iCRH secretion. Results suggest that AVP plays a relevant, multiple role in the activation of the HPA axis in the rat. In fact, interactions between AVP and the pituitary corticotroph may not be solely due to a direct effect of AVP on ACTH secretion, but also to activation of the hypothalamic CRH neuron. These effects of AVP appear to be mediated by the V-1b receptor subtype. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD USA. NIMH, CLIN NEUROENDOCRINOL BRANCH, BETHESDA, MD USA. RI Demitrack, Mark/I-7697-2013 OI bernardini, renato/0000-0002-4765-0663; NR 30 TC 22 Z9 22 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD NOV PY 1994 VL 60 IS 5 BP 503 EP 508 DI 10.1159/000126787 PG 6 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA PP398 UT WOS:A1994PP39800006 PM 7845540 ER PT J AU HOPE, BT NYE, HE KELZ, MB SELF, DW IADAROLA, MJ NAKABEPPU, Y DUMAN, RS NESTLER, EJ AF HOPE, BT NYE, HE KELZ, MB SELF, DW IADAROLA, MJ NAKABEPPU, Y DUMAN, RS NESTLER, EJ TI INDUCTION OF A LONG-LASTING AP-1 COMPLEX COMPOSED OF ALTERED FOS-LIKE PROTEINS IN BRAIN BY CHRONIC COCAINE AND OTHER CHRONIC TREATMENTS SO NEURON LA English DT Article ID IMMEDIATE-EARLY GENE; TRANSCRIPTION; SYSTEM; PHOSPHORYLATION; ACTIVATOR; MORPHINE; ANTIGEN; FORM; JUN AB Following chronic cocaine treatment, we have found a long lasting increase in AP-1 binding in the rat nucleus accumbens and striatum, two important targets of the behavioral effects of cocaine. This increase develops gradually over several days and remains at 50% of maximal levels 7 days after the last cocaine exposure. Supershift experiments, along with one and two-dimensional Western blots, indicate that this chronic AP-1 complex contains at least four Fos-related antigens (FRAs), some of which display Delta FosB-like immunoreactivity, that are induced selectively by chronic, but not acute, cocaine treatment. The same chronic FRAs were also induced by several different types of chronic treatments in a region-specific manner in the brain. Thus, the chronic FRAs and associated chronic AP-1 complex could mediate some of the long-term changes in gene expression unique to the chronic-treated state as opposed to the acute-treated and normal states. C1 YALE UNIV,SCH MED,DEPT PHARMACOL,NEW HAVEN,CT 06508. CONNECTICUT MENTAL HLTH CTR,NEW HAVEN,CT 06508. NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. KYUSHU UNIV,MED INST BIOREGULAT,DEPT BIOCHEM,FUKUOKA 812,JAPAN. RP HOPE, BT (reprint author), YALE UNIV,SCH MED,DEPT PSYCHIAT,MOLEC PSYCHIAT LAB,NEW HAVEN,CT 06508, USA. RI Kelz, Max/E-4054-2010; Hope, Bruce/A-9223-2010; Nakabeppu, Yusaku/A-8902-2011 OI Kelz, Max/0000-0002-2803-6078; Hope, Bruce/0000-0001-5804-7061; FU NIDA NIH HHS [DA00203, DA07359]; NIMH NIH HHS [MH45481] NR 20 TC 423 Z9 431 U1 1 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD NOV PY 1994 VL 13 IS 5 BP 1235 EP 1244 DI 10.1016/0896-6273(94)90061-2 PG 10 WC Neurosciences SC Neurosciences & Neurology GA PU763 UT WOS:A1994PU76300019 PM 7946359 ER PT J AU MURPHY, DGM ALLEN, G HAXBY, JV LARGAY, KA DALY, E WHITE, BJ POWELL, CM SCHAPIRO, MB AF MURPHY, DGM ALLEN, G HAXBY, JV LARGAY, KA DALY, E WHITE, BJ POWELL, CM SCHAPIRO, MB TI THE EFFECTS OF SEX STEROIDS, AND THE X-CHROMOSOME, ON FEMALE BRAIN-FUNCTION - A STUDY OF THE NEUROPSYCHOLOGY OF ADULT TURNER SYNDROME SO NEUROPSYCHOLOGIA LA English DT Review DE TURNER SYNDROME; SEX STEROIDS; COGNITIVE ABILITIES; X CHROMOSOME; VERBAL LANGUAGE; VISUOSPATIAL ABILITY; PERFORMANCE; FEMALE BRAIN FUNCTION ID CEREBRAL LATERALIZATION; GLUCOCORTICOID TOXICITY; POSTNATAL-DEVELOPMENT; COGNITIVE-DEVELOPMENT; 49,XXXXY SYNDROME; MENTAL ROTATION; MEMORY; HIPPOCAMPUS; SCHIZOPHRENIA; ASYMMETRIES AB Sex steroids and the X chromosome can independently affect cognitive abilities. Because subjects with Turner syndrome (TS) have gonadal aplasia, and Various alterations in X chromosome structure and number, they provide a model to study the effects of sex steroids and of the X chromosome on human brain function. We used neuropsychological tests to study the cognitive abilities of 18 TS adults and 19 age/sex matched healthy controls. Nine TS subjects were mosaic for the 45,X karyotype, and 9 were non-mosaic 45,X (full TS). The TS group as a whole, compared to controls, had (i) significantly lower scores in tests of language and visual-spatial function, attention and memory, and (ii) a significantly greater discrepancy between verbal and performance scores. Mosaic TS subjects were intermediate between full TS and controls in some tests of verbal ability, but did not differ significantly from controls in others. Visuospatial ability was significantly lower than controls in both mosaic and full TS. Within the mosaic TS group, there was a significant negative correlation between visuospatial ability and % lymphocytes having a 45,X karyotype. Memory test scores were reduced independently of ''X chromosome dosage'' in all TS subjects. We conclude that in humans, the X chromosome is involved in development of both cerebral hemispheres, but moreso of the association neocortices. Also, sex steroids may modulate this effect-particularly in hippocampus. C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892. NIDDK,BIOL CHEM LAB,CYTOGENET UNIT,BETHESDA,MD. NIH,MED GENET PROGRAM,BETHESDA,MD 20892. RI daly, eileen/B-6716-2011; OI Daly, Eileen/0000-0003-3625-3467 NR 108 TC 54 Z9 54 U1 2 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD NOV PY 1994 VL 32 IS 11 BP 1309 EP 1323 DI 10.1016/0028-3932(94)00065-4 PG 15 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA PT184 UT WOS:A1994PT18400001 PM 7877742 ER PT J AU HURD, YL PRISTUPA, ZB HERMAN, MM NIZNIK, HB KLEINMAN, JE AF HURD, YL PRISTUPA, ZB HERMAN, MM NIZNIK, HB KLEINMAN, JE TI THE DOPAMINE TRANSPORTER AND DOPAMINE-D-2 RECEPTOR MESSENGER-RNAS ARE DIFFERENTIALLY EXPRESSED IN LIMBIC-RELATED AND MOTOR-RELATED SUBPOPULATIONS OF HUMAN MESENCEPHALIC NEURONS SO NEUROSCIENCE LA English DT Article ID PARKINSONS-DISEASE; GENE-EXPRESSION; RAT STRIATUM; UPTAKE SITES; CLONING; AUTORECEPTORS; COCAINE; DRUGS; BRAIN; CHOLECYSTOKININ AB Dysfunction of dopamine neural systems is hypothesized to underlie neuropsychiatric disorders and psychostimulant drug abuse. At least three dopamine systems have been characterized in the brain-nigrostriatal, mesolimbic, and mesocortical, Abnormalities of nigrostriatal dopamine neurons cause motor impairment leading to Parkinson's disease, whereas dysfunction of mesolimbic and mesocortical dopamine neurons are most implicated in psychotic disorders such as schizophrenia and in drug addiction. One of the primary neural sites of action of potent antipsychotic agents and psychostimulant drugs of abuse are dopamine receptors and dopamine transporters which, respectively, mediate the induction and termination of dopamine's actions. Very limited information is, however, available about which particular set of dopaminergic cells in the human brain actually express the genes for these dopamine-specific proteins. In this study, we observed that the dopamine transporter and D-2 receptor messenger RNAs are differentially expressed within the human mesencephalon: highest expression in ventral subpopulations of the substantia nigra pars compacta neurons with lowest expression in the mesolimbic/mesocortical ventral tegmental area and retrorubral cell groups. These findings suggest that motor- and limbic-related mesencephalic neurons in the human brain differ in the degree of dopamine transporter and D-2 receptor gene expression. C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. UNIV TORONTO,DEPT PSYCHIAT,CLARKE INST PSYCHIAT,MOLEC NEUROBIOL LAB,TORONTO,ON,CANADA. FU NIDA NIH HHS [DA-07223-029] NR 35 TC 60 Z9 60 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD NOV PY 1994 VL 63 IS 2 BP 357 EP 362 DI 10.1016/0306-4522(94)90535-5 PG 6 WC Neurosciences SC Neurosciences & Neurology GA PV683 UT WOS:A1994PV68300002 PM 7891851 ER PT J AU NISENBAUM, LK KITAI, ST GERFEN, CR AF NISENBAUM, LK KITAI, ST GERFEN, CR TI DOPAMINERGIC AND MUSCARINIC REGULATION OF STRIATAL ENKEPHALIN AND SUBSTANCE-P MESSENGER-RNAS FOLLOWING STRIATAL DOPAMINE DENERVATION - EFFECTS OF SYSTEMIC AND CENTRAL ADMINISTRATION OF QUINPIROLE AND SCOPOLAMINE SO NEUROSCIENCE LA English DT Article ID CHOLINERGIC INTERNEURONS; ACETYLCHOLINE-RELEASE; GENE-EXPRESSION; RAT STRIATUM; PHENOTYPICAL CHARACTERIZATION; STRIATONIGRAL NEURONS; BRAIN MICRODIALYSIS; GLOBUS PALLIDUS; EFFERENT AXONS; RECEPTOR GENE AB Striatal dopamine depletion produces an increase in enkephalin and a decrease in substance P messenger RNAs. Subsequent systemic administration of either the D-2 dopamine agonist, quinpirole, or the muscarinic antagonist, scopolamine, results in the reduction of the lesion-induced elevation in striatal enkephalin messenger RNA. These changes in enkephalin messenger RNA levels may be mediated solely within the striatum or through trans-synaptic circuits involving the striatum. To dissociate these possibilities, we have compared the effects of systemic and central administration of quinpirole and scopolamine on striatal enkephalin and substance P messenger RNAs using in situ hybridization histochemistry. Systemic administration of both quinpirole and scopolamine blocked the elevation of striatal enkephalin messenger RNA normally observed in 6-hydroxydopamine-lesioned rats. In addition, high doses of systemic scopolamine (25 and 50 mg/kg per day) prevented the lesion-induced decrease in striatal substance P messenger RNA levels. In order to determine whether the effects of these drugs are mediated directly within the striatum, central administration of quinpirole and scopolamine were compared. In contrast to systemic administration, intraventricular and intrastriatal infusion of quinpirole but not scopolamine prevented the lesion-induced change in striatal enkephalin messenger RNA. However, neither quinpirole nor scopolamine administered centrally affected the level of substance P messenger RNA in the striatum of 6-hydroxydopamine-induced lesioned animals. Together, these data suggest that changes in D-2 receptor activation directly in the striatum are responsible for the effects of quinpirole on enkephalin messenger RNA. In contrast, the effect of systemic scopolamine on striatal enkephalin and substance P messenger RNAs may not be mediated within the striatum. C1 NIMH,NEUROANAT SECT,BETHESDA,MD 20892. RP NISENBAUM, LK (reprint author), UNIV TENNESSEE,COLL MED,DEPT ANAT & NEUROBIOL,MEMPHIS,TN 38163, USA. FU NINDS NIH HHS [NS20702] NR 45 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 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD NOV PY 1994 VL 63 IS 2 BP 435 EP 449 DI 10.1016/0306-4522(94)90541-X PG 15 WC Neurosciences SC Neurosciences & Neurology GA PV683 UT WOS:A1994PV68300008 PM 7534387 ER PT J AU HUBBARD, VS AF HUBBARD, VS TI JOINT COLLABORATION FOR WORKSHOP SO NUTRITION LA English DT Letter RP HUBBARD, VS (reprint author), NIDDK,NUTR SCI BRANCH,BETHESDA,MD, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU NUTRITION PI SYRACUSE PA PO BOX 920, SYRACUSE, NY 13210-0920 SN 0899-9007 J9 NUTRITION JI Nutrition PD NOV-DEC PY 1994 VL 10 IS 6 BP 571 EP 571 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA PY507 UT WOS:A1994PY50700016 PM 7703611 ER PT J AU HARTGE, P WHITTEMORE, AS ITNYRE, J MCGOWAN, L CRAMER, D CASAGRANDE, JT KELSEY, JL LEE, M LEE, NC LYON, JL MARSHALL, JR NASCA, PC PAFFENBARGER, RS ROSENBERG, L WEISS, NS AF HARTGE, P WHITTEMORE, AS ITNYRE, J MCGOWAN, L CRAMER, D CASAGRANDE, JT KELSEY, JL LEE, M LEE, NC LYON, JL MARSHALL, JR NASCA, PC PAFFENBARGER, RS ROSENBERG, L WEISS, NS TI RATES AND RISKS OF OVARIAN-CANCER IN SUBGROUPS OF WHITE WOMEN IN THE UNITED-STATES SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID COLLABORATIVE ANALYSIS AB Objective: To provide estimates of the age-adjusted incidence and lifetime risk of ovarian cancer in subgroups of women defined by key risk factors. Methods: We combined data from seven case-control studies (1122 cases and 5359 controls) with Surveillance, Epidemiology, and End Results incidence data to estimate the incidence rate and probability of developing ovarian cancer within subgroups of women defined according to the three major known risk factors: a history of ovarian cancer in the mother or sister, years of oral contraceptive (OC) use, and number of term pregnancies. Results: Among women with no family history of ovarian cancer, the risk at age 65 varied from 0.3% among those who had had three or more term pregnancies and 4 or more years of OC use, to 1.6% among nulliparous women with no OC use. Among women with a positive family history, the risk of developing ovarian cancer by age 65 was estimated as 4.4% and the lifetime risk as 9.4%. The data were too sparse to estimate the risks associated with OC use and pregnancy among women with a positive family history. Conclusions: The risk of developing ovarian cancer within the total population of white women can be divided informatively into component risks within subpopulations. At birth, the estimated risk of developing ovarian cancer before age 65 for the total population is 0.8%, but the component risks vary 15-fold, from 0.3 to 4.4%. C1 NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. STANFORD UNIV,SCH MED,DEPT HLTH RES & POLICY,DIV EPIDEMIOL,STANFORD,CA. GEORGE WASHINGTON UNIV,MED CTR,DEPT OBSTET & GYNECOL,DIV GYNECOL ONCOL,WASHINGTON,DC. BRIGHAM & WOMENS HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02115. NR 19 TC 57 Z9 58 U1 1 U2 2 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 NOV PY 1994 VL 84 IS 5 BP 760 EP 764 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA PN551 UT WOS:A1994PN55100005 PM 7936508 ER PT J AU TORTORA, G PEPE, S BIANCO, C BALDASSARRE, G BUDILLON, A CLAIR, T CHOCHUNG, YS BIANCO, AR CIARDIELLO, F AF TORTORA, G PEPE, S BIANCO, C BALDASSARRE, G BUDILLON, A CLAIR, T CHOCHUNG, YS BIANCO, AR CIARDIELLO, F TI THE RI-ALPHA-SUBUNIT OF PROTEIN-KINASE-A CONTROLS SERUM DEPENDENCY AND ENTRY INTO CELL-CYCLE OF HUMAN MAMMARY EPITHELIAL-CELLS SO ONCOGENE LA English DT Article ID TISSUE-SPECIFIC EXTINGUISHER; AMP BINDING-PROTEINS; I REGULATORY SUBUNIT; AMINO-ACID SEQUENCE; C-HA-RAS; GROWTH-INHIBITION; MOLECULAR-CLONING; MAMMALIAN-CELLS; DOWN-REGULATION; HL-60 LEUKEMIA AB MCP-10A, a nontransformed mammary epithelial cell line, requires a mixture of hormones and growth factors for optimal cell proliferation. In this report we show that when MCF-10A cells are cultured in serum free medium they become quiescent and accumulate in G(0)/G(1) phases of the cell cycle. Following addition of complete medium to quiescent cells, MCF-10A cells enter into the S phase within 15-18h and resume the cell cycle distribution of proliferating cells within 24 h. Measurement of RI alpha subunit of the cAMP-dependent protein kinase (PKA) shows a 10- to 15-fold increase in protein levels at 6 h following complete medium addition, thus preceding cell entry into the S phase. Retroviral vector-mediated overexpression of RI alpha, but not of RII beta or C alpha subunits of PKA, enables MCF-10A cells to grow in serum-free medium. In addition, RI alpha downregulation by specific antisense oligodeoxynucleotide treatment or following infection with a retroviral vector containing the RI alpha cDNA in antisense orientation determines growth arrest of proliferating MCF-10A cells and is able to partially block S phase entry of quiescent MCF-10A cells following complete medium addition. These results suggest that RI alpha/PKAI is involved in the control of cell cycle progression of mammary epithelial cells at a G(1) to S transition border, and that its overexpression is able to overcome serum and growth factors requirement for cell proliferation. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. RP TORTORA, G (reprint author), UNIV NAPLES FEDERICO II,FAC MED & CHIRURG,CATTEDRA ONCOL MED,I-80131 NAPLES,ITALY. RI Baldassarre, Gustavo/K-1350-2016; OI Baldassarre, Gustavo/0000-0002-9750-8825; Ciardiello, Fortunato/0000-0002-3369-4841; Budillon, Alfredo/0000-0002-6330-6053 NR 39 TC 69 Z9 69 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV PY 1994 VL 9 IS 11 BP 3233 EP 3240 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA PM658 UT WOS:A1994PM65800016 PM 7936647 ER PT J AU FISCELLA, M ZAMBRANO, N ULLRICH, SJ UNGER, T LIN, D CHO, B MERCER, WE ANDERSON, CW APPELLA, E AF FISCELLA, M ZAMBRANO, N ULLRICH, SJ UNGER, T LIN, D CHO, B MERCER, WE ANDERSON, CW APPELLA, E TI THE CARBOXY-TERMINAL SERINE-392 PHOSPHORYLATION SITE OF HUMAN P53 IS NOT REQUIRED FOR WILD-TYPE ACTIVITIES SO ONCOGENE LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; CASEIN KINASE-II; CELL-CYCLE CONTROL; MUTANT P53; GENE AMPLIFICATION; GROWTH ARREST; BINDING-SITE; DNA; TRANSCRIPTION; EXPRESSION AB Wild-type p53 functions in the G1 DNA damage checkpoint pathway by activating gene transcription and preventing cell cycle progression. Others reported that mutation of the serine 386 codon in mouse p53 abolished its ability to suppress growth. Serine 386 of murine p53 and the homologous residue of human p53, serine 392, are phosphorylated in vivo and can be phosphorylated in vitro by casein kinase II (CKII). We constructed mutants that changed serine 392 of human p53 to alanine (p53-S392A) or aspartic acid (p53S392D); cotransfection of both these mutants with a reporter gene carrying a p53-responsive element into the p53-null Saos-2 cell line activated transcription as well as did wild-type p53. Furthermore, both mutants blocked cell cycle progression after transient transfection in these cells. A stable derivative of the T98G human glioblastoma cell line was established that expressed p53-S392A in response to dexamethasone. Overexpression of this mutant activated transcription of the endogenous waf1 (also called cip1) and mdm2 genes to the same extent as wild-type p53 and also produced growth arrest. Finally, p53-S392A and p53-S392D suppressed foci formation by activated ras and adenovirus EIA oncogenes as efficiently as did wild-type p53. Thus, unlike mutants that altered the serine 15 phosphorylation site, elimination of the serine 392 phosphorylation site had no discernible effect on p53 function. We conclude that neither phosphorylation nor RNA attachment to serine 392 are required for human p53's ability to suppress cell growth or to activate transcription in vivo. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892. AMER RED CROSS,JEROME H HOLLAND LAB,ROCKVILLE,MD 20855. THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,PHILADELPHIA,PA 19107. BROOKHAVEN NATL LAB,DEPT BIOL,UPTON,NY 11973. RI Zambrano, Nicola/B-9352-2014 OI Zambrano, Nicola/0000-0001-9395-3481 FU NCI NIH HHS [CA55541, CA54140] NR 67 TC 67 Z9 67 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV PY 1994 VL 9 IS 11 BP 3249 EP 3257 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA PM658 UT WOS:A1994PM65800018 PM 7936649 ER PT J AU OTTERSON, GA KRATZKE, RA COXON, A KIM, YW KAYE, FJ AF OTTERSON, GA KRATZKE, RA COXON, A KIM, YW KAYE, FJ TI ABSENCE OF P16(INK4) PROTEIN IS RESTRICTED TO THE SUBSET OF LUNG-CANCER LINES THAT RETAINS WILDTYPE RB SO ONCOGENE LA English DT Note ID RETINOBLASTOMA GENE-PRODUCT; CELL-CYCLE; SUSCEPTIBILITY GENE; PHOSPHORYLATION; EXPRESSION; INACTIVATION; SUPPRESSION; CARCINOMA; BINDING; GROWTH AB Cell cycle dependent phosphorylation of the RB tumor suppressor protein is mediated by a family of G1 cyclin dependent kinases (cdks) and cyclins including the activated cdk4:cyclin D complex. The identification of a cdk4 inhibitor, p16(INK4), as a target for mutations in cultured tumor lines and primary tumors suggested that RB activity may be affected in these cells. We have examined 88 lung cancer lines for p16(INK4) protein expression and have observed a striking inverse correlation between the presence of p16(INK4) and wildtype RB. We demonstrated that only 6/55 (11%) of small cell lung cancer (SCLC) samples had absent p16(INK4) protein, and all 6 belonged to the rare subset of SCLC with wildtype RB expression. Conversely of 48 SCLC samples with absent or mutant RB, all showed detectable levels of p16(INK4) protein. In contrast, we observed that 23/33 (70%) of non-SCLC samples had loss of p16(INK4). Twenty-two of 26 non-SCLC lines with wildtype RB had absent p16(INK4) while 6 of 7 non-SCLC lines with absent or mutant RB had detectable p16(INK4). The inverse correlation of RB and p16(INK4) expression and the absence of p16(INK4) inactivation in RB (-/-) SCLC lines (0/48) confirms a common p16(INK4)/RB growth suppressor pathway in human cancers and provides evidence that p16(INK4), and not an adjacent gene on chromosome 9p, is a specific target for mutational events. C1 NCI,NAVY ONCOL BRANCH,BETHESDA,MD 20889. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20889. RI kaye, frederic/E-2437-2011 NR 31 TC 356 Z9 360 U1 0 U2 6 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV PY 1994 VL 9 IS 11 BP 3375 EP 3378 PG 4 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA PM658 UT WOS:A1994PM65800034 PM 7936665 ER PT J AU DAY, GL BLOT, WJ SHORE, RE SCHOENBERG, JB KOHLER, BA GREENBERG, RS LIFF, JM PRESTONMARTIN, S AUSTIN, DF MCLAUGHLIN, JK FRAUMENI, JF AF DAY, GL BLOT, WJ SHORE, RE SCHOENBERG, JB KOHLER, BA GREENBERG, RS LIFF, JM PRESTONMARTIN, S AUSTIN, DF MCLAUGHLIN, JK FRAUMENI, JF TI 2ND CANCERS FOLLOWING ORAL AND PHARYNGEAL CANCER - PATIENTS CHARACTERISTICS AND SURVIVAL PATTERNS SO ORAL ONCOLOGY-EUROPEAN JOURNAL OF CANCER PART B LA English DT Article DE 2ND PRIMARY TUMORS; ORAL CANCER; PHARYNGEAL CANCER; POPULATION-BASED; DEMOGRAPHICS; SURVIVAL ID 2ND PRIMARY TUMORS; NECK-CANCER; HEAD; TRACT AB A survey was made of second primary cancers among patients who were enrolled in a large case-control investigation of oral and pharyngeal cancer, hereafter called oral cancer, during 1984-1985 in four areas of the United States. Among the original 1090 patients with oral cancer (nearly all squamous cell carcinomas), 107 developed a second cancer (one-half of them squamous cell) by the end of follow-up in June 1989 (average follow-up 2.6 years), with 69% occurring in the oral cavity, pharynx, oesophagus, larynx or lung. Rates of second tumours varied by age and socioeconomic status, but not sex or race, and were higher among those whose initial cancer was localised, even after adjusting for their longer survival. Long-term survival was lower among those with second cancers. Conditional on surviving for 2 years, the survival at 5 years was under 50% and nearly 70%, respectively, for those with versus those without a second cancer in the first 2 years. These findings confirm the exceptionally high rate of second cancers (especially of the aerodigestive tract) following oral cancer, describe the clinical and pathological features of patients with multiple cancers and indicate the importance of preventive measures. C1 NYU,MED CTR,NEW YORK,NY 10016. NEW JERSEY DEPT HLTH,TRENTON,NJ 08625. EMORY UNIV,SCH PUBL HLTH,ATLANTA,GA 30329. UNIV SO CALIF,LOS ANGELES,CA 90033. CALIF DEPT HLTH SERV,EMERYVILLE,CA 94608. RP DAY, GL (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892, USA. NR 21 TC 15 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0964-1955 J9 ORAL ONCOL JI Oral Oncol.-Eur. J. Cancer Pt. B PD NOV PY 1994 VL 30B IS 6 BP 381 EP 386 PG 6 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA QC885 UT WOS:A1994QC88500005 ER PT J AU MEEHAN, S DAVIS, V BRAHIM, JS AF MEEHAN, S DAVIS, V BRAHIM, JS TI EMBRYONAL RHABDOMYOSARCOMA OF THE FLOOR OF THE MOUTH - A CASE-REPORT SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Note ID INTERGROUP RHABDOMYOSARCOMA; CHILDHOOD RHABDOMYOSARCOMA; CHILDREN; CHEMOTHERAPY; HEAD; NECK AB Rhabdomyosarcoma is a neoplasm composed of striated muscle. One of the most common types of soft tissue mesenchymal tumors in infants, children, and adolescents, rhabdomyosarcoma was considered an almost uniformly fatal cancer as recently as 30 years ago. Presently a multimodal approach consisting of surgery, radiation, and chemotherapy has significantly improved the outlook for the patient with rhabdomyosarcoma. This article presents a case of intraoral rhabdomyosarcoma that was initially poorly controlled because of a lack of patient compliance. After proper treatment, the cancer went into remission. The patient remained cancer-free for 7 years, albeit with significant morbidity. This case demonstrates the significantly improved prognosis achieved with multimodal therapy. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,ROOM 1N113,BETHESDA,MD 20892. NR 19 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD NOV PY 1994 VL 78 IS 5 BP 603 EP 606 DI 10.1016/0030-4220(94)90172-4 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA PR455 UT WOS:A1994PR45500013 PM 7838467 ER PT J AU REN, K AF REN, K TI WIND-UP AND THE NMDA RECEPTOR - FROM ANIMAL STUDIES TO HUMANS SO PAIN LA English DT Editorial Material ID ANTAGONIST MEMANTINE; DORSAL HORN; RAT MODEL; PAIN; NEURONS; DEXTRORPHAN; SUMMATION RP REN, K (reprint author), NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BLDG 49,ROOM 1A11,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 20 TC 58 Z9 61 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD NOV PY 1994 VL 59 IS 2 BP 157 EP 158 DI 10.1016/0304-3959(94)90067-1 PG 2 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA PR729 UT WOS:A1994PR72900001 PM 7892012 ER PT J AU REN, K WILLIAMS, GM RUDA, MA DUBNER, R AF REN, K WILLIAMS, GM RUDA, MA DUBNER, R TI INFLAMMATION AND HYPERALGESIA IN RATS NEONATALLY TREATED WITH CAPSAICIN - EFFECTS ON 2 CLASSES OF NOCICEPTIVE NEURONS IN THE SUPERFICIAL DORSAL HORN SO PAIN LA English DT Article DE NEONATAL CAPSAICIN; COMPLETE FREUNDS ADJUVANT; THERMAL HYPERALGESIA; MECHANICAL HYPERALGESIA; NOCICEPTIVE-SPECIFIC NEURON; WIDE-DYNAMIC-RANGE NEURON ID PRIMARY SENSORY NEURONS; GENE-RELATED PEPTIDE; ADJUVANT-INDUCED INFLAMMATION; TONIC DESCENDING INHIBITION; RECEPTIVE-FIELD PROPERTIES; SPINAL-CORD; SUBSTANCE-P; ADULT-RATS; UNILATERAL INFLAMMATION; NOXIOUS-STIMULATION AB To address the mechanisms of hyperalgesia and dorsal horn plasticity following peripheral tissue inflammation, the effects of adjuvant-induced inflammation of the rat hindpaw on behavioral nociception and nociceptive neuronal activity in the superficial dorsal horn were examined in neonatally capsaicin-treated rats 6-8 weeks of age. Capsaicin treatment resulted in an 82% loss of unmyelinated fibers in L5 dorsal roots, a dramatic reduction of substance P-like immunoreactivity in the spinal cord, and a significant decrease in the percentage of dorsal horn nociceptive neurons that reponded to C-fiber stimulation and noxious heating of the skin. The thermal nociceptive threshold was significantly increased in capsaicin-treated rats, but behavioral hyperalgesia to thermal stimuli still developed in response to inflammation. Following inflammation, there was a significant decrease in mechanical threshold and an increase in response duration to mechanical stimuli in both vehicle- and capsaicin-treated rats, suggesting that a state of mechanical hyperalgesia was also induced. The capsaicin treatment appears to have differential effects on nociceptive specific (NS) and wide-dynamic-range (WDR) neurons in inflamed rats. Expansion of the receptive fields of nociceptive neurons, a measure of the effect of inflammation-induced CNS plasticity, was less extensive for NS than for WDR neurons in capsaicin-treated rats. Compared to vehicle-treated rats, a smaller population of NS neurons, but a similar percentage of WDR neurons, had background activity in inflamed capsaicin-treated rats. C-fiber strength electrical stimulation of the sciatic nerve produced expansion of the receptive fields in a greater portion of NS neurons (53%, P < 0.05) in capsaicin- than in vehicle-treated rats (32%). There was no difference in stimulation-induced expansion of the receptive fields for WDR neurons between vehicle- or capsaicin-treated rats. An N-methyl-D-aspartate receptor antagonist, MK-801, attenuated the behavioral hyperalgesia and reduced the receptive field size of dorsal horn neurons in inflamed capsaicin- and vehicle-treated rats. The data suggest that while capsaicin-sensitive primary afferents may be involved in neuronal plasticity induced by peripheral tissue inflammation, changes in the capsaicin-insensitive WDR and NS populations are sufficient to produce thermal and mechanical hyperalgesia after the loss of capsaicin-sensitive primary afferents. RP REN, K (reprint author), NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BLDG 49,ROOM 1A11,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 73 TC 35 Z9 38 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD NOV PY 1994 VL 59 IS 2 BP 287 EP 300 DI 10.1016/0304-3959(94)90082-5 PG 14 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA PR729 UT WOS:A1994PR72900016 PM 7892027 ER PT J AU KRESINA, TF AF KRESINA, TF TI THE EXTRAMURAL EXOCRINE PANCREAS PROGRAM OF THE US NATIONAL-INSTITUTES-OF-HEALTH SO PANCREAS LA English DT Article DE DIGESTIVE DISEASE RESEARCH; NIH INSTITUTES AND CENTERS AB The National Institutes of Health (NIH) is the major agency in the federal government that supports both biomedical research and training in the digestive diseases as it relates to health maintenance, human development throughout life, disease prevent:ion, and disease treatment. The present article summarizes the exocrine pancreas program in the context of digestive diseases expenditures of the NIH. This article is a follow-up review of the Pancreas Program as originally described by Roussos (Pancreas 1986;1:74-79). The period covered in this review is fiscal year (FY) 1987 to present. Data presented for FY 1987 to 1992 were provided by the NIH Data Book (U.S. Public Hearth Service, 1993). Fiscal data for FY 1993-FY 1994 are compiled from institutional databases. FY 1995 figures are presented from the President's budget request submitted to the Congress of the United States. RP KRESINA, TF (reprint author), NIDDK,DDDN,PANCREAS DIS PROGRAM,WESTWOOD BLDG 3A17,45 CTR DR,MSC 6600,BETHESDA,MD 20892, USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 1994 VL 9 IS 6 BP 773 EP 780 DI 10.1097/00006676-199411000-00017 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM164 UT WOS:A1994PM16400017 PM 7846021 ER PT J AU GRACZYK, TK CRANFIELD, MR MCCUTCHAN, TF BICKNESE, EJ AF GRACZYK, TK CRANFIELD, MR MCCUTCHAN, TF BICKNESE, EJ TI CHARACTERISTICS OF NATURALLY ACQUIRED AVIAN MALARIA INFECTIONS IN NAIVE JUVENILE AFRICAN BLACK-FOOTED PENGUINS (SPHENISCUS-DEMERSUS) SO PARASITOLOGY RESEARCH LA English DT Article ID FALCIPARUM AB Antibody responses to naturally acquired Plasmodium relictum and P. elongatum infections, blood parasitemia, and disease signs were investigated in 23 naive juvenile African black-footed penguins (Spheniscus demersus). Anti-Plasmodium spp. immunoglobulins were detected by enzyme-linked immunosorbent assay (ELISA) using P. falciparum antigens. Ah birds rapidly developed antibody to P. relictum and P. elongatum. Five penguins showed detectable parasitemia and signs of the disease. Parasitemia was not related to the timing of the maximal antibody response or to the antibody titer. Two of the five parasitemic birds died and gross examination revealed splenomegaly, hepatomegaly, and congested, edematous lungs. Although the other 17 birds were clearly exposed to the disease, none showed signs of infection. No subsequent episode of parasitemia was observed in individual penguins. A comparison of the fate of 1993 penguins with those from other years showed a great variability in the proportion of birds exhibiting signs of malaria. C1 BALTIMORE ZOO,BALTIMORE,MD 21217. NIH,MALARIA RES LAB,BETHESDA,MD 20892. RP GRACZYK, TK (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT IMMUNOL & INFECT DIS,615 N WOLFE ST,BALTIMORE,MD 21205, USA. NR 16 TC 31 Z9 32 U1 0 U2 9 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0044-3255 J9 PARASITOL RES JI Parasitol. Res. PD NOV PY 1994 VL 80 IS 8 BP 634 EP 637 DI 10.1007/BF00932944 PG 4 WC Parasitology SC Parasitology GA PR728 UT WOS:A1994PR72800002 PM 7886030 ER PT J AU NACHMAN, SA MUELLER, BU MIROCHNICK, M PIZZO, PA AF NACHMAN, SA MUELLER, BU MIROCHNICK, M PIZZO, PA TI HIGH FAILURE RATE OF DAPSONE AND PENTAMIDINE AS PNEUMOCYSTIS-CARINII PNEUMONIA PROPHYLAXIS IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED CHILDREN SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Note DE DAPSONE; PNEUMOCYSTIS CARINII; PNEUMONIA PROPHYLAXIS ID TRIMETHOPRIM-SULFAMETHOXAZOLE; AEROSOLIZED PENTAMIDINE; SECONDARY PROPHYLAXIS; HIV-INFECTION; EFFICACY; MONOACETYLDAPSONE; PHARMACOKINETICS; PREVENTION; SAFETY; TRIAL C1 NCI,BETHESDA,MD 20892. BOSTON CITY HOSP,DEPT PEDIAT,BOSTON,MA 02118. RP NACHMAN, SA (reprint author), SUNY STONY BROOK,DEPT PEDIAT,STONY BROOK,NY 11794, USA. NR 31 TC 9 Z9 9 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD NOV PY 1994 VL 13 IS 11 BP 1004 EP 1006 PG 3 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA PT216 UT WOS:A1994PT21600014 PM 7845719 ER PT J AU MERICQ, V CASSORLA, F GARCIA, H AVILA, A BOWERS, C MERRIAM, G AF MERICQ, V CASSORLA, F GARCIA, H AVILA, A BOWERS, C MERRIAM, G TI GROWTH-HORMONE RESPONSES TO GROWTH-HORMONE RELEASING PEPTIDE (GRP) AND TO GROWTH-HORMONE RELEASING HORMONE (GRF) IN GROWTH-HORMONE DEFICIENT CHILDREN (GND) SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 UNIV CHILE, INST INVEST MATERNO INFANTIL, SANTIAGO, 98195, CHILE. NICHHD, DEB, BETHESDA, MD 70118 USA. UNIV WASHINGTON, SEATTLE, WA USA. TULANE UNIV, NEW ORLEANS, LA USA. RI Mericq, Veronica/F-3927-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD NOV PY 1994 VL 36 IS 5 BP 672 EP 672 DI 10.1203/00006450-199411000-00025 PG 1 WC Pediatrics SC Pediatrics GA PP801 UT WOS:A1994PP80100022 ER PT J AU DOMENE, HM YU, YM MARIN, G SZTEIN, J CASSORLA, F AF DOMENE, HM YU, YM MARIN, G SZTEIN, J CASSORLA, F TI DIFFERENTIAL REGULATION OF GROWTH-HORMONE RECEPTOR EXPRESSION BY ESTRADIOL AND TESTOSTERONE SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD. RI Sztein, Jorge/B-7165-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD NOV PY 1994 VL 36 IS 5 BP 677 EP 677 DI 10.1203/00006450-199411000-00058 PG 1 WC Pediatrics SC Pediatrics GA PP801 UT WOS:A1994PP80100055 ER PT J AU SALAZAR, T DOMENE, H YU, Y SZTEIN, J HUMPHREYS, S CASSORLA, F AF SALAZAR, T DOMENE, H YU, Y SZTEIN, J HUMPHREYS, S CASSORLA, F TI EFFECTS OF THYROID-HORMONE ON GROWTH-HORMONE RECEPTOR (GHR) AND IGF-I EXPRESSION SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,DEB,BETHESDA,MD. RI Sztein, Jorge/B-7165-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD NOV PY 1994 VL 36 IS 5 BP 680 EP 680 DI 10.1203/00006450-199411000-00069 PG 1 WC Pediatrics SC Pediatrics GA PP801 UT WOS:A1994PP80100066 ER PT J AU MERICQ, V CASSORLA, F GARCIA, H AVILA, A BORIC, A MERRIAM, G AF MERICQ, V CASSORLA, F GARCIA, H AVILA, A BORIC, A MERRIAM, G TI CHRONIC BETA-ADRENERGIC-BLOCKADE ENHANCES GROWTH VELOCITY TO GROWTH-HORMONE RELEASING HORMONE IN GROWTH-HORMONE DEFICIENT CHILDREN (GHD) SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,BETHESDA,MD. UNIV CHILE,DEB,IDIMI,SANTIAGO,CHILE. RI Mericq, Veronica/F-3927-2010 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD NOV PY 1994 VL 36 IS 5 BP 682 EP 682 DI 10.1203/00006450-199411000-00081 PG 1 WC Pediatrics SC Pediatrics GA PP801 UT WOS:A1994PP80100078 ER PT J AU MUELLER, BU BUTLER, KM STOCKER, VL BALIS, FM BROUWERS, P JAROSINSKI, P HUSSON, RN LEWIS, LL VENZON, D PIZZO, PA AF MUELLER, BU BUTLER, KM STOCKER, VL BALIS, FM BROUWERS, P JAROSINSKI, P HUSSON, RN LEWIS, LL VENZON, D PIZZO, PA TI CLINICAL AND PHARMACOKINETIC EVALUATION OF LONG-TERM THERAPY WITH DIDANOSINE IN CHILDREN WITH HIV-INFECTION SO PEDIATRICS LA English DT Article DE HIV; DIDANOSINE; SURVIVAL; TOXICITIES; CD4 COUNTS; PHARMACOKINETICS; CHILD ID AIDS-RELATED COMPLEX; IMMUNODEFICIENCY-VIRUS INFECTION; PHASE-I TRIAL; ZIDOVUDINE THERAPY; 2',3'-DIDEOXYINOSINE DDI; DIDEOXYINOSINE; TOXICITY; COMBINATION; CD4 AB Background. Didanosine has demonstrated promising antiviral activity and a tolerable toxicity profile in short term studies. We describe a cohort of HIV-infected children who were treated for a prolonged period of time with didanosine. Methods. Children(6 months to 18 years of age) with symptomatic HIV infection or an absolute CD4 count < 0.5 x 10(9) cells/L, received oral didanosine at doses between 20 mg/m(2) to 180 mg/m(2) every 8 hours. Clinical, immunological, and virological parameters were assessed at least every 2 months. The pharmacokinetics of didanosine were evaluated in 85 patients. Results. Previously untreated children (n = 51) and children who had received prior antiretroviral therapy (n = 52) were enrolled in the study (median time on study 22.6 months; range 2 to 48). The long-term administration of didanosine was well tolerated and no new toxicities were observed. The absolute CD4 count increased by greater than or equal to .05 x 10(9) cells/L in 28 of 87 (32%) of patients after 6 months of therapy. Responses were also sustained in 41% of these children after 3 years of therapy. Children entering the study with a CD4 count > 0.1 x 10(9) cells/L (n = 51) had a marked survival advantage (P = .00002) with an estimated survival probability after 3 years of 80% compared to 39% for children with lower CD4 counts. Although the area under the curve of didanosine increased proportionally with the dose, there was considerable interpatient variability at each dose level. There was no apparent relationship between surrogate markers of clinical outcome and plasma drug concentration. Conclusions. Didanosine was well tolerated with chronic administration, and toxicities were uncommon and usually reversible. In 41% of patients, the CD4 count increased and was maintained at the higher level even after years of treatment. C1 NCI,PEDIAT BRANCH,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. NCI,WARREN GRANT MAGNUSON CLIN CTR,DEPT PHARM,BETHESDA,MD 20892. NCI,CLIN ONCOL PROGRAM,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 26 TC 31 Z9 31 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 1994 VL 94 IS 5 BP 724 EP 731 PG 8 WC Pediatrics SC Pediatrics GA PN912 UT WOS:A1994PN91200013 PM 7936903 ER PT J AU HALL, CB CHESNEY, PJ GROMISCH, DS HALSEY, NA KOHL, S MARCY, SM MARKS, MI NANKERVIS, GA OVERALL, JC PICKERING, LK STEELE, RW YOGEV, R AF HALL, CB CHESNEY, PJ GROMISCH, DS HALSEY, NA KOHL, S MARCY, SM MARKS, MI NANKERVIS, GA OVERALL, JC PICKERING, LK STEELE, RW YOGEV, R TI ADMINISTRATION OF THE 3RD DOSE OF ORAL POLIOMYELITIS VACCINE AT 6 TO 18 MONTHS OF AGE SO PEDIATRICS LA English DT Article ID TRIVALENT POLIOVIRUS VACCINES; IMMUNIZATION C1 CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. US FDA,WASHINGTON,DC 20204. AMER THORAC SOC,NEW YORK,NY. CANADIAN PAEDIAT SOC,OTTAWA,ON,CANADA. NIH,BETHESDA,MD 20892. NATL VACCINE PROGRAM,ROCKVILLE,MD. NR 13 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 1994 VL 94 IS 5 BP 774 EP 775 PG 2 WC Pediatrics SC Pediatrics GA PN912 UT WOS:A1994PN91200028 ER PT J AU ROTHMAN, RB GORELICK, DA BAUMANN, MH GUO, XY HERNING, RI PICKWORTH, WB GENDRON, TM KOEPPL, B THOMSON, LE HENNINGFIELD, JE AF ROTHMAN, RB GORELICK, DA BAUMANN, MH GUO, XY HERNING, RI PICKWORTH, WB GENDRON, TM KOEPPL, B THOMSON, LE HENNINGFIELD, JE TI LACK OF EVIDENCE FOR CONTEXT-DEPENDENT COCAINE-INDUCED SENSITIZATION IN HUMANS - PRELIMINARY STUDIES SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE COCAINE; BEHAVIORAL SENSITIZATION; CLASSICAL CONDITIONING; PROLACTIN; CORTISOL; ENDOCRINE EFFECTS ID BEHAVIORAL SENSITIZATION; NEUROENDOCRINE RESPONSES; DOPAMINE; EXTINCTION; INJECTIONS; PROLACTIN; RELEASE AB Cocaine-induced behavioral sensitization is the well-documented phenomenon where repeated doses of cocaine elicit increasingly greater effects on motoric activity in rats. Some observations suggest that behavioral sensitization may provide a model for understanding the mechanisms of drug-craving elicited by environmental triggers or cues. The process of fully validating such an animal model for its ability to detect effective anticraving medicines is a difficult and long-term undertaking. As a first step in that direction, we decided to determine if cocaine can produce conditioned behavioral sensitization in humans using a paradigm fairly similar to that used for rodents. Because humans do not react to cocaine with the pronounced motor activation observed in rodents, we measured a variety of end points, including blood pressure (BP), heart rate (HR), respiratory rate, pupil diameter, hormones (prolactin and cortisol), and subjective responses using the questionnaire for drug-related feelings (QDRF) and the EEG. To mimic the home and test cages used in rodent studies, two rooms were used: a small test chamber and a regular room with a window and furnishings. On day 1 each subject received a drug infusion (either saline or 40 mg cocaine IV) in both locations. On day 2, all subjects received an infusion (saline or 25 mg cocaine IV) in the test chamber. All drug infusions were conducted double blind. The paired group received cocaine on both days in the test chamber. The unpaired group received cocaine in regular room on day 1, and cocaine in the test chamber on day 2. A control-1 group received saline at both locations on day 1, and cocaine on day 2 in the test chamber. A control-2 group [4] received cocaine in the test chamber on day 1 and saline in the test chamber on day 2. Conditioned-sensitization was not observed. However, conditioned tolerance was observed for cocaine-induced changes in plasma prolactin levels and diastolic blood pressure. Because rodent studies use cocaine-naive subjects and this study used cocaine-experienced subjects, these data suggest that prior experience with cocaine may alter it ability to produce sensitization. Viewed collectively, the present investigation suggests caution in the design of both human and animal studies. RP ROTHMAN, RB (reprint author), NIDA,ADDICT RES CTR,CLIN PHARMACOL SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 36 TC 33 Z9 33 U1 0 U2 4 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 NOV PY 1994 VL 49 IS 3 BP 583 EP 588 DI 10.1016/0091-3057(94)90073-6 PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA PN294 UT WOS:A1994PN29400021 PM 7862712 ER PT J AU GEWISS, MV MARLEY, RJ THORNDIKE, EB GOLDBERG, SR SCHINDLER, CW AF GEWISS, MV MARLEY, RJ THORNDIKE, EB GOLDBERG, SR SCHINDLER, CW TI GABA RECEPTOR-LINKED CHLORIDE CHANNELS AND THE BEHAVIORAL-EFFECTS OF NALTREXONE IN RATS SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE NALTREXONE; GABA AGONISTS; GABA ANTAGONISTS; PENTOBARBITAL; PICROTOXIN; SCHEDULE-CONTROLLED BEHAVIOR; RATS ID ENHANCED SENSITIVITY; NALOXONE; ANTAGONIST; RESPONSES AB The present study was conducted to determine whether the effects of naltrexone on schedule-controlled behavior in rats were mediated, at least in part, by the GABAergic system. Because the enhanced sensitivity that has been shown to occur following naltrexone treatment might alter the effects of the treatment compounds, a variety of compounds interacting with the GABA system were tested in both sensitized and nonsensitized animals. Of all the compounds tested in this manner, only the dose-effect function for the GABAA agonist muscimol was altered by the naltrexone treatment, with the higher doses of muscimol producing response-rate decreasing effects only in naltrexone-sensitized rats. In the naltrexone-treated animals, these same GABA agonists and antagonists were used as pretreatments prior to the determination of the naltrexone dose-effect function. Although shifts in the naltrexone dose-effect function were observed, the effects were not consistent either within or across receptor class. In contrast, the chloride-channel antagonist picrotoxin clearly shifted the naltrexone dose-effect function in sensitized animals to the left, while the chloride-channel facilitator pentobarbital shifted the function to the right. These results indicate that the effects of naltrexone are at least partially mediated by an action at the GABA-linked chloride channel, rather than directly at the GABA receptor. C1 NIDA,ADDICT RES CTR,BEHAV PHARMACOL & GENET SECT,PRECLIN PHARMACOL LAB,BALTIMORE,MD 21224. NIDA,ADDICT RES CTR,MOLEC NEUROBIOL BRANCH,BALTIMORE,MD 21224. NR 25 TC 12 Z9 12 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD NOV PY 1994 VL 49 IS 3 BP 589 EP 597 DI 10.1016/0091-3057(94)90074-4 PG 9 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA PN294 UT WOS:A1994PN29400022 PM 7862713 ER PT J AU AULAKH, CS TOLLIVER, T WOZNIAK, KM HILL, JL MURPHY, DL AF AULAKH, CS TOLLIVER, T WOZNIAK, KM HILL, JL MURPHY, DL TI FUNCTIONAL AND BIOCHEMICAL-EVIDENCE FOR ALTERED SEROTONERGIC FUNCTION IN THE FAWN-HOODED RAT STRAIN SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE M-CPP; DOI; IPSAPIRONE; RECTAL TEMPERATURE; GROWTH HORMONE; GENETIC MODEL; DEPRESSION; SUBSENSITIVE ID GROWTH-HORMONE RELEASE; SPRAGUE-DAWLEY RATS; DEPRESSED-PATIENTS; META-CHLOROPHENYLPIPERAZINE; 5-HT1C RECEPTORS; HEALTHY-SUBJECTS; BINDING-SITES; BRAIN; RESPONSES; 8-OH-DPAT AB Administration of various doses of DOI (a 5-HT2A/5-HT2C agonist) produced hyperthermia that was significantly less in the FH rat strain relative to the Wistar rat strain. Similarly, administration of various doses of ipsapirone (a 5-HT1A agonist) produced hypothermia that was significantly less in the FH rat strain relative to the Wistar rat strain. Furthermore, m-CPP (a 5-HT agonist)-induced increases in growth hormone levels were also significantly less in the FH rat strain relative to the Wistar rat strain. There was no significant difference in the levels of either 5-HT or 5-HIAA between the two rat strains in the frontal cortex, hippocampus, hypothalamus, and striatum. In the brain stem, however, both 5-HT and 5-HIAA levels were significantly lower in the FH rat strain relative to the Wistar rat strain. On the other hand, 5-HT turnover rate was significantly higher in the hypothalamus and striatum and significantly lower in the hippocampus in the FH rat strain relative to the Wistar rat strain. These findings provide further evidence for altered serotonergic function in the FH rat strain and, in addition, suggest that the FH rat strain may prove to be a useful genetic model for some neuropsychiatric disorders with possible abnormalities in serotonergic function such as depression, obsessive-compulsive disorder, and the eating disorders. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PHYSIOL & PHARMACOL,WINSTON SALEM,NC 27157. RP AULAKH, CS (reprint author), NIMH,CTR CLIN,CLIN SCI LAB,BLDG 10,RM 3D41,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 37 TC 35 Z9 37 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD NOV PY 1994 VL 49 IS 3 BP 615 EP 620 DI 10.1016/0091-3057(94)90077-9 PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA PN294 UT WOS:A1994PN29400025 PM 7532310 ER PT J AU FINKELSTEIN, JE HENGEMIHLE, JM INGRAM, DK PETRI, HL AF FINKELSTEIN, JE HENGEMIHLE, JM INGRAM, DK PETRI, HL TI MILACEMIDE TREATMENT IN MICE ENHANCES ACQUISITION OF A MORRIS-TYPE WATER MAZE TASK SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE GLYCINE RECEPTOR; NMDA RECEPTOR; MEMORY; LONG-TERM POTENTIATION; SPATIAL LEARNING ID D-ASPARTATE RECEPTOR; LONG-TERM POTENTIATION; NMDA RECEPTORS; GLYCINE PRODRUG; MODULATORY SITE; LEARNING-TASKS; D-CYCLOSERINE; MEMORY; HIPPOCAMPUS; PERFORMANCE AB The N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor appears to be involved with processes of learning and memory. A neutral amino acid binding site is known to exist on the NMDA complex. Glycine binds with high affinity to this site and has been found to potentiate NMDA activity. 2-N-Pentylaminoacetamide HCl (milacemide) is a glycine agonist that has been found to enhance performance of rodents in passive and active avoidance tasks and has improved the performance of humans in several word retrieval tasks. We evaluated the effects of milacemide on the performance of male C57BL/6J mice in a complex spatial task, the Morris water maze. Because NMDA receptor activation appears involved in induction Of long-term potentiation, if was hypothesized that milacemide administration would be involved in task acquisition. Therefore, mice were treated with either milacemide (10 mg/kg) or vehicle 1 h prior to training on each of 4 consecutive days. Results indicated that mice treated with milacemide learned the task significantly faster than controls over 4 days of training, as measured by mean distance (cm) to reach the goal platform. Therefore, agonism of the glycine site on the NMDA receptor appears to facilitate performance of learning in a spatial memory task. C1 NIA,GERONTOL RES CTR,NATHAN W SHOCK LABS,MOLEC PHYSIOL & GENET SECT,BALTIMORE,MD 21224. TOWSON STATE UNIV,DEPT PSYCHOL,BALTIMORE,MD 21204. NR 26 TC 20 Z9 20 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD NOV PY 1994 VL 49 IS 3 BP 707 EP 710 DI 10.1016/0091-3057(94)90091-4 PG 4 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA PN294 UT WOS:A1994PN29400039 PM 7862727 ER PT J AU AULAKH, CS HILL, JL MURPHY, DL AF AULAKH, CS HILL, JL MURPHY, DL TI ENHANCED ANOREXIC RESPONSES TO M-CHLOROPHENYLPIPERAZINE DURING LITHIUM ADMINISTRATION TO FAWN-HOODED RATS SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Note DE M-CPP; FOOD INTAKE; FAWN-HOODED RAT; SEROTONIN; DEPRESSION ID NEURO-ENDOCRINE RESPONSES; SPRAGUE-DAWLEY RATS; SEROTONIN UPTAKE; HORMONE-RELEASE; DEPRESSION; BRAIN; DECREASES; RECEPTORS; WISTAR; TERM AB In the present study, we investigated whether functional adaptational changes in the serotonergic neurotransmitter mechanisms regulating food intake following long-term lithium treatment in Fawn-Hooded rats (a rat strain suggested to represent a genetic model of depression) were different or similar to those previously observed in Wistar rats. Long-term (21-25 days) lithium treatment accentuated m-chlorophenylpiperazine (m-CPP, a 5-HT agonist) induced decreases in food intake. There was no significant difference in either brain m-CPP concentrations or hypothalamic norepinephrine, dopamine and 5-hydroxyindoleacetic acid concentrations between control and long-term lithium-treated rats following m-CPP. However, hypothalamic serotonin concentrations were significantly higher in long-term lithium-treated compared to saline-treated animals. This finding contrasts with our previous report demonstrating attenuation of m-CPP-induced anorexia in Wistar rats following similar long-term lithium treatment, and therefore suggests a differential adaptation in the serotonergic neurotransmitter mechanisms regulating food intake in a genetic animal model of depression. RP AULAKH, CS (reprint author), NIMH,CTR CLIN,CLIN SCI LAB,BLDG 10,RM 3D41,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 20 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 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD NOV PY 1994 VL 49 IS 3 BP 759 EP 762 DI 10.1016/0091-3057(94)90098-1 PG 4 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA PN294 UT WOS:A1994PN29400046 PM 7862734 ER PT J AU MYERS, CE ZELLMER, WA FRIEDMAN, MK CULHANE, MB VALENTINO, JG ALBERS, ES BARBACCIA, JG DECHRISTOFORO, R FORTNER, CL AF MYERS, CE ZELLMER, WA FRIEDMAN, MK CULHANE, MB VALENTINO, JG ALBERS, ES BARBACCIA, JG DECHRISTOFORO, R FORTNER, CL TI DEVELOPMENT OF A SYMBOL FOR HAZARDOUS DRUG PRODUCTS SO PHARMACOPEIAL FORUM LA English DT Article C1 NATL WHOLESALE DRUGGISTS ASSOC,DIV DISTRIBUT LOGIST,ALEXANDRIA,VA 22314. ONCOL NURSING SOC,PITTSBURGH,PA. US PHARMACOPEIAL CONVENT INC,ROCKVILLE,MD. ALBERS INC,KNOXVILLE,TN. WASHINGTON HOSP CTR,DEPT PHARM,WASHINGTON,DC. NIH,CTR CLIN,DEPT PHARM,CLIN PHARM SERV,BETHESDA,MD. RP MYERS, CE (reprint author), AMER SOC HOSP PHARMACISTS,DIV PROFESS PRACTICE & SCI AFFAIRS,7272 WISCONSIN AVE,BETHESDA,MD 20814, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU US PHARMACOPEIAL CONVENTION PI ROCKVILLE PA 12601 TWINBROOK PKWY, ROCKVILLE, MD 20852 SN 0363-4655 J9 PHARMACOPEIAL FORUM JI Pharmacop. Forum PD NOV-DEC PY 1994 VL 20 IS 6 BP 8575 EP 8578 PG 4 WC Medicine, Legal; Pharmacology & Pharmacy SC Legal Medicine; Pharmacology & Pharmacy GA PT403 UT WOS:A1994PT40300005 ER PT J AU WLODAWER, A AF WLODAWER, A TI RATIONAL DRUG DESIGN - THE PROTEINASE-INHIBITORS SO PHARMACOTHERAPY LA English DT Article AB Human immunodeficiency virus (HIV) proteinase is a promising target for the rational development of drugs against the acquired immunodeficiency syndrome (AIDS), since this enzyme is necessary for viral maturation, and its inhibition could lead to cessation of viral replication. Rational drug design combines chemical synthesis of compounds with structure determination methods, including protein crystallography. When the crystal structure of the HIV proteinase was determined, many research laboratories began designing drugs that would be effective inhibitors of the enzyme, and many such inhibitors were produced. Once that work was initiated, refined, and completed in the laboratory, other issues, such as specificity and bioavailability, became important. The clinical utility of such compounds is the final and most important consideration. Analysis of many agents for which structural formulas have been determined, and comparison of such formulas, provide valuable lessons for the continuing work on this enzyme and for future programs of rational drug design. RP WLODAWER, A (reprint author), NCI,FCRDC,MACROMOLEC STRUCT LAB,BLDG 539,POB B,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101] NR 1 TC 14 Z9 14 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD NOV-DEC PY 1994 VL 14 IS 6 BP S9 EP S20 PN 2 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PU654 UT WOS:A1994PU65400003 PM 7885983 ER PT J AU RESZKA, KJ CHIGNELL, CF AF RESZKA, KJ CHIGNELL, CF TI PHOTOCHEMISTRY OF 2-MERCAPTOPYRIDINES .1. AN EPR AND SPIN-TRAPPING INVESTIGATION USING 5,5-DIMETHYL-1-PYRROLINE N-OXIDE IN AQUEOUS AND TOLUENE SOLUTIONS SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID FLASH-PHOTOLYSIS; IRON CHELATORS; CELL-LINES; RADICALS; N-HYDROXY-2-THIOPYRIDONE; DERIVATIVES; TAUTOMERISM; GENERATION; SYSTEMS; OXYGEN AB We have employed EPR and the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) to investigate the photochemistry of pyridine-2-thione (2-S-PyrH), N-hydroxypyridine-2-thione (2-S-PyrNOH), and its sodium salt, (2-S-PyrNONa), and disulfides, 2,2'-dithiobis (pyridine N-oxide) [(2-S-PyrN-->O)(2)] and 2,2'-dithiodipyridine [(2-S-Pyr)(2)]. We have found that upon UV irradiation they generate aromatic thiyl radicals, 2-S-.-Pyr and 2-S-.-PyrN-->O, detected as DMPO adducts, DMPO/2-S-.-Pyr (1) and DMPO/2-S-.-PyrN-->O (2). In aqueous solution (pH 7) hyperfine splitting constants (hfsc) were determined to be for 1: a(N) = 14.92 G, a(H)(beta) = 16.57 G, and for 2: a(N) = 14.78 G, a(H)(beta) = 16.05 G. In toluene hfsc were 13.09 G, 13.93 G for 1, and 13.25 G, 12.04 G for 2. Irradiation of 2-S-PyrH and DMPO in aerated pH 7 buffer generated the DMPO/O-.(2)- radical (3a, a(N) = 14.10 G, a(H)(beta) = 11.40 G, a(H)(gamma) = 1.18 G), while in aerated toluene DMPO/(O2H)-O-. was formed (adduct 3b, a(N) = 12.74 G, a(H)(beta) = 10.41 G, a(H)(gamma) = 1.295 G). In both systems adduct 1 was also observed. Because compounds possessing the pyridine-2-thione moiety show antifungal, antibacterial and anticancer properties, it is likely that the ability to photogenerate free radicals may be pertinent to their biological activity. RP RESZKA, KJ (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 47 TC 14 Z9 14 U1 0 U2 6 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 NOV PY 1994 VL 60 IS 5 BP 442 EP 449 DI 10.1111/j.1751-1097.1994.tb05131.x PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PR258 UT WOS:A1994PR25800009 ER PT J AU RESZKA, KJ CHIGNELL, CF AF RESZKA, KJ CHIGNELL, CF TI PHOTOCHEMISTRY OF 2-MERCAPTOPYRIDINES .2. AN EPR AND SPIN-TRAPPING INVESTIGATION USING 2-METHYL-2-NITROSOPIROPANE AND ACI-NITROMETHANE AS SPIN TRAPS IN AQUEOUS-SOLUTIONS SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID HYDROXYL RADICALS; IRON CHELATORS; CELL-LINES; PHOTOLYSIS; DERIVATIVES; GENERATION; RESONANCE AB Compounds possessing a pyridine-2-thione moiety show antimicrobial, antifungal and anticancer activities. Some of them are also photochemically active and upon UV irradiation generate free radicals. In this work, employing EPR and the spin traps 2-methyl-2-nitrosopropane (MNP) and aci-nitromethane (NM), we investigated the photochemistry in aqueous solutions of N-hydroxypyridine-2-thione (used here as a sodium salt, 2-S-PyrNONa), and pyridine-2-thione (2-S-PryH), as well as photochemistry of the respective disulfides, 2,2'-dithiobis(pyridine N-oxide) [(2-S-PyrN-->O)(2)] and 2,2'-dithiodipyridine [(2-S-Pyr)(2)]. We found that UV irradiation of 2-S-PyrNONa and of 2-S-PyrH in the presence of MNP and NM generates EPR signals of reduced spin traps in addition to signals of MNP and NM adducts with aryl-thiyl radicals, 2-S-.-PyrN-->O and 2-S-.-Pyr. The identification of the aromatic thiyl radicals was based on comparison of EPR spectra of spin adducts generated by irradiation of 2-S-PyrNONa and 2-S-PyrH with those produced by UV photolysis of the respective disulfides (2-S-PyrN-->O)(2) and (2-S-Pyr)(2). It is concluded that pyridine-2-thione and N-hydroxypyridine-2-thione possess a photoreducing capacity and generate aromatic thiyl radicals upon UV activation. This property may be relevant to biological action of agents containing the pyridine-2-thione moiety. RP RESZKA, KJ (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 33 TC 13 Z9 13 U1 0 U2 1 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 NOV PY 1994 VL 60 IS 5 BP 450 EP 454 DI 10.1111/j.1751-1097.1994.tb05132.x PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PR258 UT WOS:A1994PR25800010 PM 7800716 ER PT J AU SHIMAKAWA, T SORLIE, P CARPENTER, MA DENNIS, B TELL, GS WATSON, R WILLIAMS, OD AF SHIMAKAWA, T SORLIE, P CARPENTER, MA DENNIS, B TELL, GS WATSON, R WILLIAMS, OD TI DIETARY-INTAKE PATTERNS AND SOCIODEMOGRAPHIC FACTORS IN THE ATHEROSCLEROSIS RISK IN COMMUNITIES STUDY SO PREVENTIVE MEDICINE LA English DT Article ID UNITED-STATES POPULATION; NATIONAL-HEALTH; YOUNG-ADULTS; CHOLESTEROL; MORTALITY; CARDIA; EDUCATION; BLACK; FIBER; RACE AB Background. Comprehensive and up-to-date data on differences in dietary intake according to various sociodemographic factors are needed to understand the potential impact of dietary factors on disease risks in the United States. Methods. Usual dietary intake assessed by a food frequency questionnaire was examined in relation to race, sex, and educational attainment using baseline data obtained from randomly selected samples of 15,800 middle-aged black and white men and women who participated in the Atherosclerosis Risk in Communities Study. Results. In almost all comparisons, higher educational attainment was associated with recommended dietary intake patterns-lower per energy intakes of meats, eggs, chicken with skin, and whole milk and higher intakes of fruits, vegetables, fish, chicken without skin, and low-fat milk. As expected from these food intake patterns, higher educational attainment was associated with lower intakes of saturated fatty acid and cholesterol and with higher intakes of dietary fiber and various micronutrients. Compared with women's diets, men's diets were slightly more atherogenic (in whites only) based upon Keys score and had lower micronutrient levels. Although there were large differences in the food intakes between blacks and whites, the differences in nutrient intakes were generally smaller. However, intakes of cholesterol and vitamin A were somewhat higher and intakes of saturated fatty acid, calcium, and potassium were lower among blacks than in whites. Conclusions. This community-based study clearly demonstrated that regardless of race and sex, high educational attainment is associated with recommended dietary intake patterns. Continuing efforts to improve general educational level and to promote healthy dietary habits among those with low socioeconomic status are warranted. (C) 1994 Academic Press, Inc. C1 UNIV N CAROLINA,CTR COLLABORAT STUDIES COORDINATING,DEPT BIOSTAT,CHAPEL HILL,NC. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. UNIV MISSISSIPPI,MED CTR,DIV EPIDEMIOL,JACKSON,MS 39216. UNIV ALABAMA,SCH PUBL HLTH,BIRMINGHAM,AL 35294. RP SHIMAKAWA, T (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,FED BLDG,ROOM 2C03,7550 WISCONSIN AVE,BETHESDA,MD 20892, USA. RI Tell, Grethe/G-5639-2015 OI Tell, Grethe/0000-0003-1386-1638 FU NHLBI NIH HHS [N01-HC-55018, N01-HC-55019, N01-HC-55020] NR 41 TC 97 Z9 98 U1 0 U2 6 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD NOV PY 1994 VL 23 IS 6 BP 769 EP 780 DI 10.1006/pmed.1994.1133 PG 12 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA PU102 UT WOS:A1994PU10200001 PM 7855109 ER PT J AU SANKARAPANDI, S RIFKIND, JM MANOHARAN, PT AF SANKARAPANDI, S RIFKIND, JM MANOHARAN, PT TI THERMODYNAMICS OF SOME LONG-CHAIN BIRADICALS STUDIED BY EPR SPECTROSCOPY SO PROCEEDINGS OF THE INDIAN ACADEMY OF SCIENCES-CHEMICAL SCIENCES LA English DT Article DE BIRADICALS; EPR SPECTROSCOPY; SIMULATION; THERMODYNAMIC PARAMETERS; CONFORMATIONAL CHANGES; FAST AND SLOW EXCHANGES ID SPECTRA AB Four biradicals of differing chain lengths have been prepared by spin-labelling the sulphhydryl groups of dithiothreitol. Temperature-dependent EPR spectra of these biradicals indicate that the dynamics of biradicals is associated with both fast and slow exchanges of conformations. The three-conformational model incorporating cage configuration is found to be more appropriate. Certain thermodynamic parameters of conformational changes have been calculated from the experimental EPR parameters, obtained by the use of simulation procedures developed recently. C1 INDIAN INST TECHNOL,DEPT CHEM,MADRAS 600036,TAMIL NADU,INDIA. NIA,GERONTOL RES CTR,MOLEC & CELLULAR BIOL LAB,BALTIMORE,MD 21224. NR 21 TC 10 Z9 10 U1 1 U2 2 PU INDIAN ACADEMY SCIENCES PI BANGALORE PA P B 8005 C V RAMAN AVENUE, BANGALORE 560 080, INDIA SN 0253-4134 J9 P INDIAN AS-CHEM SCI JI Proc. Indian Acad. Sci.-Chem. Sci. PD NOV PY 1994 VL 106 IS 6 BP 1329 EP 1340 PG 12 WC Chemistry, Multidisciplinary SC Chemistry GA QN586 UT WOS:A1994QN58600010 ER PT J AU GRACE, WC AF GRACE, WC TI HIV COUNSELING RESEARCH NEEDS SUGGESTED BY PSYCHOTHERAPY PROCESS AND OUTCOME STUDIES SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article ID LIMITED DYNAMIC PSYCHOTHERAPY; RISK-REDUCTION; BEHAVIORAL-RESEARCH; SOCIAL-INFLUENCE; AIDS PREVENTION; ADOLESCENTS; THERAPY; HYPOTHESIS; ADHERENCE; PROGRAM AB HIV risk reduction counseling is commonly used to prevent the spread of HIV. Such counseling is an interpersonal process that shares many characteristics with psychotherapy. Research on HIV counseling can benefit from methods and findings from psychotherapy research, and scientist-practitioners are well qualified to design or collaborate in studies that incorporate their expertise in psychotherapeutic process and in research. Studies of the relationship between the counselor and client, the structure of the counseling sessions, client experiences, and specific intervention techniques are suggested on the basis of consistent findings and important themes in psychotherapy literature. Research findings from studies adapting techniques and results from psychotherapy studies could significantly improve the effectiveness of current risk reduction counseling. C1 NIDA,LEXINGTON,KY 40583. NR 73 TC 3 Z9 3 U1 5 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0735-7028 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD NOV PY 1994 VL 25 IS 4 BP 403 EP 409 DI 10.1037//0735-7028.25.4.403 PG 7 WC Psychology, Multidisciplinary SC Psychology GA PT422 UT WOS:A1994PT42200016 ER PT J AU MYERS, RB OELSCHLAGER, D SRIVASTAVA, S GRIZZLE, WE AF MYERS, RB OELSCHLAGER, D SRIVASTAVA, S GRIZZLE, WE TI ACCUMULATION OF THE P53 PROTEIN OCCURS MORE FREQUENTLY IN METASTATIC THAN IN LOCALIZED PROSTATIC ADENOCARCINOMAS SO PROSTATE LA English DT Article DE PIN; IMMUNOHISTOCHEMISTRY; ANTIGEN RETRIEVAL SOLUTION ID CELLULAR TUMOR-ANTIGEN; PREMALIGNANT LESION; GENE-MUTATIONS; TRANSFORMATION; CARCINOMAS; CANCER; DELETIONS; NEOPLASIA; TARGET; MUTANT AB Mutations of the p53 gene result in increased stability and accumulation of the p53 protein, permitting p53 protein detection by immunohistochemical techniques. We have utilized immunohistochemistry to examine accumulation of the p53 protein at various stages of progression in prostatic adenocarcinomas. p53 protein accumulation was detected using the monoclonal antibody BP53-12-1 in 3 of 28 (11%) localized prostatic adenocarcinomas, and in prostatic intraepithelial neoplasia (PIN) in 1 of 16 (6%) specimens. In contrast, p53 protein was detected in 9 of 16 (56%) primary prostatic adenocarcinomas that were metastatic (stage D), and in 10 of 18 (56%) matching metastases to lymph nodes from these same patients. Thus, we observed a higher incidence of p53 protein accumulation in matching primary and metastatic lesions of patients with stage D adenocarcinoma than in localized (nonmetastatic) adenocarcinomas. We also found that an antigen retrieval solution (ARS) aided in the detection of p53 protein accumulation in prostatic adenocarcinomas. The results indicate that accumulation of p53 protein occurs prior to metastasis, and identifies a subclass of prostatic adenocarcinomas that express a high potential for metastasis. (C) 1994 Wiley-Liss, Inc. C1 UNIV ALABAMA,DEPT PATHOL,BIRMINGHAM,AL 35294. VET ADM MED CTR,DEPT PATHOL,BIRMINGHAM,AL. NCI,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CN-15340-02] NR 21 TC 43 Z9 43 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 0270-4137 J9 PROSTATE JI Prostate PD NOV PY 1994 VL 25 IS 5 BP 243 EP 248 DI 10.1002/pros.2990250504 PG 6 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA QH322 UT WOS:A1994QH32200003 PM 7971515 ER PT J AU SAWYER, JR SCHLOM, J KASHMIRI, SVS AF SAWYER, JR SCHLOM, J KASHMIRI, SVS TI THE EFFECTS OF INDUCTION CONDITIONS ON PRODUCTION OF A SOLUBLE ANTITUMOR SFV IN ESCHERICHIA-COLI SO PROTEIN ENGINEERING LA English DT Article DE BACTERIAL EXPRESSION; PERIPLASMIC LOCALIZATION; PROTEIN AGGREGATION; SINGLE-CHAIN ANTIBODIES ID SINGLE-CHAIN FV; ANTIGEN-BINDING; BETA-LACTAMASE; PROTEIN; FRAGMENTS; SECRETION; PERIPLASM; GENES AB CC49 is a second generation monoclonal antibody (mAb) with high affinity to a pancarcinoma antigen, TAG-72. A single-chain Fv (sFv) of CC49 may have a role in managing human carcinomas. Most reported sFvs have been expressed as insoluble products that must be solubilized and renatured. Soluble sFv expression is advantageous as activity can be assayed directly from the periplasmic fraction. Also, gene-level immunoconjugates may not be amenable to refolding protocols. Using a vector that carries the tac promoter and omp A signal, we have examined the effects of four variables on the expression and accumulation of soluble CC49 sFv: (i) linker sequence joining V-L and V-H, (ii) isopropylthio-beta-D-galactoside concentration for induction, (iii) temperature, and (iv) the addition of nonmetabolizable sugars to the medium. We have been able to demonstrate, using rapidly prepared periplasmic extracts, that the yield of soluble sFv improves by the addition of 0.4 M sucrose to the medium and by inducing expression with a very low concentration of IPTG (0.02-0.03 mM). Under these induction conditions periplasmic extracts demonstrate increased,expression of the sFv, as shown by the larger amount of a 27 kDa band on SDS-polyacrylamide gel, and an increased ability to inhibit binding of the mAb CC49 to immobilized tumor extracts. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NR 19 TC 30 Z9 33 U1 1 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD NOV PY 1994 VL 7 IS 11 BP 1401 EP 1406 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA PT100 UT WOS:A1994PT10000015 PM 7700873 ER PT J AU KUSZEWSKI, J CLORE, GM GRONENBORN, AM AF KUSZEWSKI, J CLORE, GM GRONENBORN, AM TI FAST FOLDING OF A PROTOTYPIC POLYPEPTIDE - THE IMMUNOGLOBULIN BINDING DOMAIN OF STREPTOCOCCAL PROTEIN-G SO PROTEIN SCIENCE LA English DT Article DE FOLDING INTERMEDIATES; PROTEIN FOLDING; QUENCHED-FLOW DEUTERIUM HYDROGEN EXCHANGE ID GROUP HYDROGEN-EXCHANGE; 2-DIMENSIONAL NMR; PATHWAYS; EVENTS; B2; B1 AB The folding of the small (56 residues) highly stable B1 immunoglobulin binding domain (GB1) of streptococcal protein G has been investigated by quenched-flow deuterium-hydrogen exchange. This system represents a paradigm for the study of protein folding because it exhibits no complicating features superimposed upon the intrinsic properties of the polypeptide chain. Collapse to a semicompact state exhibiting partial order, reflected in protection factors for ND-NH exchange up to 10-fold higher than that expected for a random coil, occurs within the dead time (less than or equal to 1 ms) of the quenched flow apparatus. This is followed by the formation of the fully native state, as monitored by the fractional proton occupancy of 26 backbone amide groups spread throughout the protein, in a single rapid concerted step with a half-life of 5.2 ms at 5 degrees C. C1 NIDDKD,PHYS CHEM LAB,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 45 TC 118 Z9 119 U1 0 U2 8 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 NOV PY 1994 VL 3 IS 11 BP 1945 EP 1952 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PZ824 UT WOS:A1994PZ82400006 PM 7703841 ER PT J AU KOONIN, EV MUSHEGIAN, AR TATUSOV, RL ALTSCHUL, SF BRYANT, SH BORK, P VALENCIA, A AF KOONIN, EV MUSHEGIAN, AR TATUSOV, RL ALTSCHUL, SF BRYANT, SH BORK, P VALENCIA, A TI EUKARYOTIC TRANSLATION ELONGATION-FACTOR 1-GAMMA CONTAINS A GLUTATHIONE TRANSFERASE DOMAIN - STUDY OF A DIVERSE, ANCIENT PROTEIN SUPERFAMILY USING MOTIF SEARCH AND STRUCTURAL MODELING SO PROTEIN SCIENCE LA English DT Article DE CONSERVED SEQUENCE MOTIFS; GLUTATHIONE S-TRANSFERASE DOMAIN; MOTIF SEARCH; STRUCTURE MODELING; TRANSLATION ELONGATION FACTOR 1-GAMMA ID TRANSFER-RNA-SYNTHETASE; SITE-DIRECTED MUTAGENESIS; STRINGENT STARVATION PROTEIN; DISULFIDE BOND FORMATION; MOLECULAR-MASS COMPLEX; AMINO-ACID-SEQUENCES; S-TRANSFERASE; 3-DIMENSIONAL STRUCTURE; FACTOR-I; ESCHERICHIA-COLI AB Using computer methods for multiple alignment, sequence motif search, and tertiary structure modeling, we show that eukaryotic translation elongation factor 1 gamma (EF1 gamma) contains an N-terminal domain related to class theta glutathione S-transferases (GST). GST-Iike proteins related to class theta comprise a large group including, in addition to typical GSTs and EF1 gamma, stress-induced proteins from bacteria and plants, bacterial reductive dehalogenases and beta-etherases, and several uncharacterized proteins. These proteins share 2 conserved sequence motifs with GSTs of other classes (alpha, mu, and pi). Tertiary structure modeling showed that in spite of the relatively low sequence similarity, the GST-related domain of EF1 gamma is likely to form a fold very similar to that in the known structures of class alpha, mu, and pi GSTs. One of the conserved motifs is implicated in glutathione binding, whereas the other motif probably is involved in maintaining the proper conformation of the GST domain. We predict that the GST-like domain in EF1 gamma is enzymatically active and that to exhibit GST activity, EF1 gamma has to form homodimers. The GST activity may be involved in the regulation of the assembly of multisubunit complexes containing EF1 and aminoacyl-tRNA synthetases by shifting the balance between glutathione, disulfide glutathione, thiol groups of cysteines, and protein disulfide bonds. The GST domain is a widespread, conserved enzymatic module that may be covalently or noncovalently complexed with other proteins. Regulation of protein assembly and folding may be 1 of the functions of GST. C1 UNIV KENTUCKY, DEPT PLANT PATHOL, LEXINGTON, KY 40546 USA. EUROPEAN MOLEC BIOL LAB, W-6900 HEIDELBERG, GERMANY. RP NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20894 USA. RI Bork, Peer/F-1813-2013 OI Bork, Peer/0000-0002-2627-833X NR 74 TC 104 Z9 105 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0961-8368 EI 1469-896X J9 PROTEIN SCI JI Protein Sci. PD NOV PY 1994 VL 3 IS 11 BP 2045 EP 2054 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PZ824 UT WOS:A1994PZ82400017 PM 7703850 ER PT J AU COVELL, DG SMYTHERS, GW GRONENBORN, AM CLORE, GM AF COVELL, DG SMYTHERS, GW GRONENBORN, AM CLORE, GM TI ANALYSIS OF HYDROPHOBICITY IN THE ALPHA-CHEMOKINE AND BETA-CHEMOKINE FAMILIES AND ITS RELEVANCE TO DIMERIZATION SO PROTEIN SCIENCE LA English DT Article DE ALPHA AND BETA CHEMOKINES; CHEMOTACTIC CYTOKINES; DIMERIC STRUCTURE; HMIP-1-BETA; HYDROPHOBICITY; INTERLEUKIN-8; TERTIARY STRUCTURE ID 3-DIMENSIONAL STRUCTURE; CRYSTAL-STRUCTURES; PLATELET FACTOR-4; CYTOKINE FAMILY; PROTEIN; INTERLEUKIN-8; CONFORMATIONS; BINDING AB The chemokine family of chemotactic cytokines plays a key role in orchestrating the immune response. The family has been divided into 2 subfamilies, alpha and beta, based on the spacing of the first 2 cysteine residues, function, and chromosomal location. Members within each subfamily have 25-70% sequence identity, whereas the amino acid identity between members of the 2 subfamilies ranges from 20 to 40%. A quantitative analysis of the hydrophobic properties of 11 alpha and 9 beta chemokine sequences, based on the coordinates of the prototypic alpha and beta chemokines, interleukin-8 (IL-8), and human macrophage inflammatory protein-1 beta (hMIP-1 beta), respectively, is presented. The monomers of the alpha and beta chemokines have their strongest core hydrophobic cluster at equivalent positions, consistent with their similar tertiary structures. In contrast, the pattern of monomer surface hydrophobicity between the alpha and beta chemokines differs in a manner that is fully consistent with the observed differences in quaternary structure. The most hydrophobic surface clusters on the monomer subunits are located in very different regions of the alpha and beta chemokines and comprise in each case the amino acids that are buried at the interface of their respective dimers. The theoretical analysis of hydrophobicity strongly supports the hypothesis that the distinct dimers observed for IL-8 and hMIP-1 beta are preserved for all the alpha and beta chemokines, respectively. This provides a rational explanation for the lack of receptor crossbinding and reactivity between the alpha and beta chemokine subfamilies. C1 NIDDKD,PHYS CHEM LAB,BETHESDA,MD 20892. RP COVELL, DG (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOMED SUPERCOMP LAB,FREDERICK,MD 21702, USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 27 TC 26 Z9 26 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 NOV PY 1994 VL 3 IS 11 BP 2064 EP 2072 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PZ824 UT WOS:A1994PZ82400019 PM 7703852 ER PT J AU ZHU, PP REIZER, J PETERKOFSKY, A AF ZHU, PP REIZER, J PETERKOFSKY, A TI UNIQUE DICISTRONIC OPERON (PTSI-CRR) IN MYCOPLASMA CAPRICOLUM ENCODING ENZYME-I AND THE GLUCOSE-SPECIFIC ENZYME-IIA OF THE PHOSPHOENOLPYRUVATE, SUGAR PHOSPHOTRANSFERASE SYSTEM - CLONING, SEQUENCING, PROMOTER ANALYSIS, AND PROTEIN CHARACTERIZATION SO PROTEIN SCIENCE LA English DT Article DE ENZYME I; GLUCOSE-SPECIFIC ENZYME IIA; MYCOPLASMA; OPERON STRUCTURE; PHOSPHOENOLPYRUVATE, SUGAR PHOSPHOTRANSFERASE SYSTEM ID ESCHERICHIA-COLI K-12; NUCLEOTIDE-SEQUENCE; BACILLUS-SUBTILIS; RECEPTOR PROTEIN; BGL OPERON; GENE; BINDING; ACETYLGLUCOSAMINE; IDENTIFICATION; TRANSCRIPTION AB The region of the genome of Mycoplasma capricolum encompassing the genes for Enzymes I and IIA(glc) of the phosphoenolpyruvate:sugar phosphototransferase system (PTS) was cloned and sequenced. Examination of the sequence revealed a unique arrangement of the pts operon. In all other bacterial species characterized thus far, the gene encoding Enzyme I (ptsI) in the pts operon is locate immediately downstream of the gene (ptsH) encoding HPr, a general energy coupling protein of the PTS. In M. capricolum, ptsH and ptsI reside on 2 distinct operons at separate loci on the chromosome (Zhu PP, Reizer J, Reizer A, Peterkofsky A, 1993, J Biol Chem 268:26531-26540). In the present work, it is shown that the Mycoplasma Enzyme I gene is preceded by an open reading frame homologous to the product of the Escherichia coli kdtB gene and is followed by the gene (crr) encoding Enzyme IIA(glc). Northern blot analysis indicated that ptsI and crr constitute a dicistronic operon that includes an independent promoter for the crr gene. Primer extension studies established the transcription start sites for the ptsI and crr genes. The products of the ptsI and crr genes are homologous to previously sequences Enzymes I and IIA(glc) proteins but are more similar to the counterpart proteins from gram-positive than those from gram-negative organisms. The deduced amino acid sequence of the Mycoplasma Enzyme I shows that it differs from other Enzymes I by having fewer acidic amino acids and more basic, amidated, and aromatic amino acids. The deduced amino acid sequence of the Mycoplasma Enzyme IIA(glc) indicates that it is the shortest (154 residues) of the proteins in this class and its is the only Enzyme IIA(glc) with a tryptophan and a cysteine residue. In vitro sugar phosphorylation studies with extracts from E. coli and Bacillus subtilis and purified proteins indicated that the Mycoplasma HPr is not a phosphoacceptor from the E. coli Enzyme I, whereas the Mycoplasma Enzyme IIA(glc) accepts and transfers phosphate from both E. coli and B. subtilis PTS components. C1 NHLBI, BIOCHEM GENET LAB, BETHESDA, MD 20892 USA. UNIV CALIF SAN DIEGO, DEPT BIOL, LA JOLLA, CA 92093 USA. FU NIAID NIH HHS [2RO1AI4176, 5RO1AI21702] NR 51 TC 19 Z9 25 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0961-8368 EI 1469-896X J9 PROTEIN SCI JI Protein Sci. PD NOV PY 1994 VL 3 IS 11 BP 2115 EP 2128 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PZ824 UT WOS:A1994PZ82400025 PM 7703858 ER PT J AU SCHMIDT, ME KRUESI, MJP ELIA, J BORCHERDING, BG ELIN, RJ HOSSEINI, JM MCFARLIN, KE HAMBURGER, S AF SCHMIDT, ME KRUESI, MJP ELIA, J BORCHERDING, BG ELIN, RJ HOSSEINI, JM MCFARLIN, KE HAMBURGER, S TI EFFECT OF DEXTROAMPHETAMINE AND METHYLPHENIDATE ON CALCIUM AND MAGNESIUM CONCENTRATION IN HYPERACTIVE BOYS SO PSYCHIATRY RESEARCH LA English DT Article DE ATTENTION DEFICIT DISORDER; AMPHETAMINE; PLASMA; ERYTHROCYTES ID MONONUCLEAR BLOOD-CELLS; DIVALENT-CATIONS; RAT-BRAIN; INHIBITION; BINDING; SYNAPTOSOMES; BEHAVIORS; RECEPTORS; CHANNELS; LITHIUM AB Levels of calcium in plasma, red blood cells, and mononuclear blood cells, levels of calcium in plasma, and the plasma calcium-to-magnesium ratio were measured at baseline and after 3 weeks of each drug phase of a double-blind, placebo-controlled study of methylphenidate and dextroamphetamine in hyperactive boys. Levels of magnesium in plasma were significantly higher after 3 weeks of dextroamphetamine treatment, and the calcium-to-magnesium ratio was significantly lower after 3 weeks of either drug compared with the baseline or placebo condition. There was no change in magnesium levels in red blood cells or mononuclear blood cells. These measures were obtained 30 minutes before the morning dose and at 9 a.m., 9:30 a.m., 10:30 a.m., 11:00 a.m., and noon on the last day of each 3-week phase. Analysis of variance revealed a drug effect on plasma magnesium and on the calcium-to-magnesium ratio but no drug X time interaction. Although these changes were not correlated with the time course of acute symptomatic response to stimulant therapy, the decrease in the ratio may be relevant to side effects and treatment resistance associated with stimulant use. C1 UNIV ILLINOIS,INST JUVENILE RES,CHICAGO,IL. EASTERN PENN PSYCHIAT INST,PHILADELPHIA,PA. NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. FREDERICK MED CTR,FREDERICK,MD. UNIV MARYLAND,COLLEGE PK,MD 20742. NIH,CTR CLIN,BETHESDA,MD 20892. RP SCHMIDT, ME (reprint author), NIMH,EXPTL THERAPEUT BRANCH,CLIN PHARMACOL SECT,BLDG 10,RM 2D46,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Schmidt, Mark/I-5052-2016 OI Schmidt, Mark/0000-0003-3417-8977 NR 54 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCI PUBL 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 NOV PY 1994 VL 54 IS 2 BP 199 EP 210 DI 10.1016/0165-1781(94)90007-8 PG 12 WC Psychiatry SC Psychiatry GA QH915 UT WOS:A1994QH91500007 PM 7761553 ER PT J AU GEORGE, MS LYDIARD, RB AF GEORGE, MS LYDIARD, RB TI SOCIAL PHOBIA SECONDARY TO PHYSICAL-DISABILITY - A REVIEW OF BENIGN ESSENTIAL TREMOR (BET) AND STUTTERING SO PSYCHOSOMATICS LA English DT Review ID ANXIETY; NONSTUTTERERS; STRESS; SPEECH AB Persons with physical disabilities cannot be diagnosed as having social phobia under current DSM-III-R criteria. The DSM-III-R social phobia diagnosis excludes persons where a physical disorder causes the distress and phobic avoidance. However, the authors have noted in clinical practice that social phobia and physical disabilities sometimes coexist. A review of the published literature reveals that stutterers and BET patients frequently have social phobia-like symptoms. No prevalence data on comorbid DSM-III-R-defined social phobia were found in these groups (i.e., social phobia occurring in areas where the disability does not cause the distress and avoidance). Further research is warranted to determine the prevalence of social phobic behaviors occurring in conjunction with certain physical disabilities. C1 MED UNIV S CAROLINA,DEPT PSYCHIAT & BEHAV SCI,CHARLESTON,SC 29425. RP GEORGE, MS (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,RM 3N212,BETHESDA,MD 20892, USA. NR 49 TC 26 Z9 27 U1 3 U2 5 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD NOV-DEC PY 1994 VL 35 IS 6 BP 520 EP 523 PG 4 WC Psychiatry; Psychology SC Psychiatry; Psychology GA PN752 UT WOS:A1994PN75200002 PM 7809354 ER PT J AU GREBERMAN, SB WADA, K AF GREBERMAN, SB WADA, K TI SOCIAL AND LEGAL FACTORS RELATED TO DRUG-ABUSE IN THE UNITED-STATES AND JAPAN SO PUBLIC HEALTH REPORTS LA English DT Article ID PREVALENCE; ASIA AB This article is an overview of social and legal differences in the United States and in Japan that are related to patterns of current drug abuse epidemics in these countries. These two nations have drug abuse problems with different histories and take different approaches currently to handling illicit drug marketing and use. Histories of opiate and cocaine abuse in the United States and of stimulant and inhalant abuse in Japan are discussed. The United States has experienced three heroin epidemics in the last three decades; cocaine addiction began to merit national concern by the end of the 1980s. In Japan, the first methamphetamine epidemic began after World War II; it was controlled in the 1950s. The current inhalant epidemic began in the late 1960s and was followed by the second methamphetamine epidemic that began in 1970; both are continuing to the present. The criminal justice system is always given first consideration when assessing societal measures employed to reduce drug use. Legal penalties for illicit drug offenses reflect the societal differences of these two nations with respect to the seriousness of particular types of crimes. Characteristics of the health care system of a nation may also influence patterns of drug abuse, particularly where functions of criminal justice and health care systems overlap. Health care systems in the United States and in Japan are based on different treatment philosophies and patients' expectations; these differences are discussed along with explanations of their potential influence on the epidemiology of drug abuse. RP GREBERMAN, SB (reprint author), NIDA,ADDICT RES CTR,TREATMENT BRANCH,POB 5180,BALTIMORE,MD 21224, USA. NR 42 TC 32 Z9 32 U1 0 U2 4 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD NOV-DEC PY 1994 VL 109 IS 6 BP 731 EP 737 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PY035 UT WOS:A1994PY03500004 PM 7800780 ER PT J AU LILLQUIST, PP ALCIATI, MH BAPTISTE, M NASCA, PC KERNER, JF METTLIN, C AF LILLQUIST, PP ALCIATI, MH BAPTISTE, M NASCA, PC KERNER, JF METTLIN, C TI CANCER CONTROL PLANNING AND ESTABLISHMENT OF PRIORITIES FOR INTERVENTION BY A STATE HEALTH DEPARTMENT SO PUBLIC HEALTH REPORTS LA English DT Article ID BREAST-CANCER; MORTALITY AB A number of data sources routinely available to State health departments were analyzed as part of a State health department cancer control planning effort. This planning effort consisted of seven steps; the most challenging one was the establishment of priorities for cancer control interventions. Using data from available sources, however, a framework for prioritizing potential cancer control interventions as well as choosing a geographic area in which to implement selected interventions was developed. Factors considered in this framework for setting intervention priorities included the magnitude of the problem; the existence of scientific consensus regarding the efficacy of intervention techniques; the availability of data needed to plan, implement, and evaluate an intervention; the availability of resources within communities to implement an intervention; and the existence of public demand for the intervention. The development and use of this cancer control planning model and framework for setting cancer control intervention priorities in New York State are described in this paper. In using this planning model and framework for setting priorities, quantitative elements were found to be most necessary to define problems, but qualitative elements were most crucial for decision making. C1 NCI,PUBL HLTH SERV,PUBL HLTH AGCY SECT,BETHESDA,MD 20892. UNIV MASSACHUSETTS,DEPT EPIDEMIOL BIOSTAT & EPIDEMIOL,AMHERST,MA 01003. GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. ROSWELL PK CANC INST,BUFFFALO,NY. RP LILLQUIST, PP (reprint author), NEW YORK STATE DEPT HLTH,BUR CANC EPIDEMIOL,CORNING TOWER,RM 536,EMPIRE STATE PLAZA,ALBANY,NY 12237, USA. OI Alciati, Marianne/0000-0001-6294-1090 FU NCI NIH HHS [1 RO1 CA 4658601] NR 13 TC 1 Z9 1 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD NOV-DEC PY 1994 VL 109 IS 6 BP 791 EP 803 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PY035 UT WOS:A1994PY03500013 PM 7800789 ER PT J AU BUFFALO, B GAFFAN, D MURRAY, EA AF BUFFALO, B GAFFAN, D MURRAY, EA TI A PRIMACY EFFECT IN MONKEYS WHEN LIST POSITION IS RELEVANT SO QUARTERLY JOURNAL OF EXPERIMENTAL PSYCHOLOGY SECTION B-COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY LA English DT Article ID FORNIX TRANSECTION; RHESUS-MONKEYS; MEMORY; RECENCY; HIPPOCAMPUS; VARIABILITY; AMNESIA AB In Experiment 1 (1a and 1b), Rhesus monkeys (Macaca mulatta) learned lists of two-choice visual discriminations in which list position was relevant to discrimination performance. For example, Stimulus A was the rewarded stimulus if it was presented at List Position 1, but was not rewarded if it was presented at any other position in the list; similarly, Stimulus B was rewarded only at List Position 2, and so on. In learning these lists, all animals showed a marked primacy effect. In Experiment 2 (2a and 2b), Rhesus monkeys and Cynomolgus monkeys (M. fascicularis) learned lists of visual discriminations in which each visual stimulus occupied a fixed position in a list, but list position was not relevant to discrimination performance. For example, Stimulus E was always rewarded, and was always presented at List Position 1. To increase the salience of list beginning as a distinctive event, successive presentations of the list were separated by 24-hr intervals. In Experiment 2 there was no primacy effect, however. These results show for the first time that a primacy effect can be obtained in visual discrimination learning by monkeys. Furthermore, they suggest that it is obtained only when list position is relevant to the discrimination learning task. C1 UNIV OXFORD,DEPT EXPTL PSYCHOL,OXFORD OX1 3UD,ENGLAND. NIMH,BETHESDA,MD 20892. OI Murray, Elisabeth/0000-0003-1450-1642 NR 20 TC 6 Z9 6 U1 1 U2 4 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0272-4995 J9 Q J EXP PSYCHOL-B JI Q. J. Exp. Psychol. Sect. B-Comp. Physiol. Psychol. PD NOV PY 1994 VL 47 IS 4 BP 353 EP 369 PG 17 WC Psychology, Biological; Physiology; Psychology; Psychology, Experimental SC Psychology; Physiology GA PT055 UT WOS:A1994PT05500001 PM 7809402 ER PT J AU HUANG, SZ REN, ZR CHEN, MJ XU, HP ZENG, YT RODGERS, GP ZENG, FY SCHECHTER, AN AF HUANG, SZ REN, ZR CHEN, MJ XU, HP ZENG, YT RODGERS, GP ZENG, FY SCHECHTER, AN TI TREATMENT OF BETA-THALASSEMIA WITH HYDROXYUREA (HU) - EFFECTS OF HU ON GLOBIN GENE EXPRESSION SO SCIENCE IN CHINA SERIES B-CHEMISTRY LIFE SCIENCES & EARTH SCIENCES LA English DT Article DE BETA-THALASSEMIA; GLOBIN GENE; EXPRESSION; HYDROXYUREA ID SICKLE-CELL-ANEMIA AB A newly developed method of RT-PCR/competitive PCR for measuring the relative and absolute content of globin mRNAs as well as micro-globin chain biosynthetic assay have been used to study the alterations of globin gene expressions in the patients with beta-thalassemia pre- and post-hydroxyurea (HU) treatment. It was found for the first time that HU had the effect of enhancing beta-globin gene expression in some patients. Two cases with beta-thalassemia who were subjected to HU treatment for over two years showed a marked increase in beta-globin mRNA lever and beta-globin chain synthesis, resulting in more effective erythropoiesis and the alleviation of clinical symptoms. C1 SHANGHAI CHILDRENS HOSP,SHANGHAI INST MED GENET,SHANGHAI 200040,PEOPLES R CHINA. NIDDKD,BIOL CHEM LAB,BETHESDA,MD 20892. OI Schechter, Alan N/0000-0002-5235-9408 FU NHLBI NIH HHS [HLB-29623] NR 14 TC 14 Z9 14 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 1001-652X J9 SCI CHINA SER B JI Sci. China Ser. B-Chem. Life Sci. Earth Sci. PD NOV PY 1994 VL 37 IS 11 BP 1350 EP 1359 PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA QB495 UT WOS:A1994QB49500009 PM 7865126 ER PT J AU SHERMAN, A MASCAGNI, M AF SHERMAN, A MASCAGNI, M TI A GRADIENT RANDOM-WALK METHOD FOR 2-DIMENSIONAL REACTION-DIFFUSION EQUATIONS SO SIAM JOURNAL ON SCIENTIFIC COMPUTING LA English DT Article DE MONTE-CARLO METHOD; REACTION-DIFFUSION EQUATION; GRADIENT TRANSPORT; GRID-FREE; ADAPTIVE; N-BODY PROBLEM ID PARTICLE-METHOD; VORTEX METHODS; APPROXIMATION; CONVERGENCE; SIMULATION; ALGORITHM AB An extension to two space dimensions of the gradient random walk algorithm for reaction-diffusion equations is presented. This family of algorithms is related closely to the random vortex method of computational fluid dynamics. Although the computational cost is high, the method has the desirable features of being grid free and of automatically adapting to the solution by concentrating elements where the gradient is large. In addition, the method can be extended easily to more than two space dimensions. A key feature of the method is discretization in terms of the dependent, rather than independent, variable, giving it features in common with Lagrangian particle methods. The method is derived here and its application to some simple reaction-diffusion wave propagation problems is illustrated. C1 INST DEF ANAL,SUPERCOMP RES CTR,BOWIE,MD 20715. RP SHERMAN, A (reprint author), NIDDKD,MATH RES BRANCH,BETHESDA,MD 20892, USA. NR 27 TC 6 Z9 6 U1 0 U2 0 PU SIAM PUBLICATIONS PI PHILADELPHIA PA 3600 UNIV CITY SCIENCE CENTER, PHILADELPHIA, PA 19104-2688 SN 1064-8275 J9 SIAM J SCI COMPUT JI SIAM J. Sci. Comput. PD NOV PY 1994 VL 15 IS 6 BP 1280 EP 1293 DI 10.1137/0915078 PG 14 WC Mathematics, Applied SC Mathematics GA PP626 UT WOS:A1994PP62600002 ER PT J AU WILLIAMS, KS TEMECK, BK PASS, HI AF WILLIAMS, KS TEMECK, BK PASS, HI TI INTRAPERICARDIAL PHEOCHROMOCYTOMA COMPLICATED BY MASSIVE INTRAOPERATIVE HEMORRHAGE SO SOUTHERN MEDICAL JOURNAL LA English DT Note ID INTRAVENOUS CALCIUM-CHLORIDE; CARDIAC PHEOCHROMOCYTOMAS; SURGICAL-TREATMENT; LOCATION; PATIENT AB Middle mediastinal pheochromocytomas are exceedingly rare. Because so few cases have been reported, consensus has not been reached regarding the anesthetic management of patients with these tumors. The use of cardiopulmonary bypass (CPB) for the resection of intrapericardial pheochromocytomas has met with varied success. We report the first documented case of successful anesthetic and surgical management of an acute, massive hemorrhage during the dissection of an intrapericardial pheochromocytoma, which was managed without cardiopulmonary bypass. Perioperative anesthetic considerations, including the risks and benefits of CPB, are discussed. C1 NCI,DIV CANC TREATMENT,SURG BRANCH,BETHESDA,MD 20892. RP WILLIAMS, KS (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT ANESTHESIOL,ANESTHESIA SECT,BLDG 10,ROOM 2C624,BETHESDA,MD 20892, USA. NR 27 TC 2 Z9 3 U1 0 U2 0 PU SOUTHERN MEDICAL ASSN PI BIRMINGHAM PA 35 LAKESHORE DR PO BOX 190088, BIRMINGHAM, AL 35219 SN 0038-4348 J9 SOUTHERN MED J JI South.Med.J. PD NOV PY 1994 VL 87 IS 11 BP 1164 EP 1167 DI 10.1097/00007611-199411000-00024 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA PR087 UT WOS:A1994PR08700024 PM 7973908 ER PT J AU DUNBAR, CE EMMONS, RVB AF DUNBAR, CE EMMONS, RVB TI GENE-TRANSFER INTO HEMATOPOIETIC PROGENITOR AND STEM-CELLS - PROGRESS AND PROBLEMS SO STEM CELLS LA English DT Review DE RETROVIRUS; ADENOASSOCIATED VIRUS; PARVOVIRIDAE; GENE THERAPY; GENETIC DISEASE; REVIEW STEM CELL; HEMATOPOIESIS ID HUMAN ADENOSINE-DEAMINASE; LONG-TERM EXPRESSION; BONE-MARROW CELLS; MURINE LEUKEMIA-VIRUS; HUMAN GAMMA-GLOBIN; ADENOASSOCIATED VIRUS; RETROVIRAL VECTOR; HUMAN GLUCOCEREBROSIDASE; RECONSTITUTED MICE; TRANSDUCTION AB Gene transfer to hematopoietic cells for the purpose of (''gene therapy'' is a new and rapidly developing field with clinical trials in progress. A fundamental goal of research in this field is the incorporation of exogenous genes into the chromosomes of the most primitive hematopoietic progenitor cells-stem cells. Recombinantly engineered retroviral vectors are the best characterized and are currently the only vector type in clinical trials directed at the hematopoietic system. High efficiency gene transfer and expression in murine stem cells and their progeny is now routine, but in larger ani mal models such as dogs or primates and preliminary clinical trials, gene transfer has been less successful. Problems such as retroviral efficiency, gene expression, insertional mutagenesis and helper virus contamination are being addressed. A promising new vector, the adeno-associated virus (AAV), has shown promise and may allow production of high titer, stable, recombinant virions without helper contamination and with potentially better safety parameters. However, the technology for AAV gene transfer is currently underdeveloped, and issues related to the reproducible production of vectors must be addressed. Other non-viral vector systems are being explored, but little data are available on applications to hematopoietic cells. Better preclinical models are needed to study gene targeting and expression in human cells. An overview of recombinant retroviral and adeno-associated viral vector production, preclinical data and preliminary clinical data will be given, and problems needing to be addressed at all stages of development before broad clinical utility can be achieved will be discussed. RP DUNBAR, CE (reprint author), NHLBI,HEMATOL BRANCH,9000 ROCKVILLE PIKE,BLDG 10,7C103,BETHESDA,MD 20892, USA. NR 98 TC 65 Z9 65 U1 3 U2 4 PU ALPHAMED PRESS PI DAYTON PA 4100 S KETTERING BLVD, DAYTON, OH 45439-2092 SN 1066-5099 J9 STEM CELLS JI Stem Cells PD NOV PY 1994 VL 12 IS 6 BP 563 EP 576 PG 14 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA PU149 UT WOS:A1994PU14900004 PM 7881358 ER PT J AU RAO, PN CESSAC, JW KIM, HK AF RAO, PN CESSAC, JW KIM, HK TI PREPARATIVE CHEMICAL METHODS FOR AROMATIZATION OF 19-NOR-DELTA(4)-3-OXOSTEROIDS SO STEROIDS LA English DT Article DE COPPER(II) BROMIDE; CERIC AMMONIUM NITRATE; IODINE; AROMATIZATION; 19-NOR-DELTA(4)-3-OXOSTEROIDS AB Two preparative chemical methods for aromatization of 19-nor-Delta(4)-3-oxosteroids are described. The first method consists of an oxidative aromatization of 19-nor-Delta(4)-3-oxosteroids with iodine-eerie ammonium nitrate in methanol to give a mixture of 3-methoxy ring-A aromatized derivatives consisting of the desired product, the Delta(9,11) derivative, the 6-oxo derivative as well as some ring-A iodinated material. Conversion of this material to a mixture of the 3-methoxy ring-A aromatized derivative and its 6-oxo derivative was achieved by catalytic hydrogenation. Finally, reduction of the 6-oxo function with triethylsilane in trifluoroacetic acid gave the 3-methoxy-17-trifluoroacetate ring-A aromatized derivative as a single product. In the second method, reaction of 19-nor-Delta(4)-3-oxosteroids with copper(II) bromide in acetonitrile at room temperature resulted in aromatic steroids in a single step in excellent yields. The second method was used in the first practical chemical synthesis of a 6-dehydroestrogen from a 19-nor-Delta(4,6)-3-oxosteroid. C1 NICHHD,BETHESDA,MD. RP RAO, PN (reprint author), SW FDN BIOMED RES,DEPT ORGAN CHEM,POB 28147,SAN ANTONIO,TX 78228, USA. FU NICHD NIH HHS [N01-HD-1-3137] NR 22 TC 28 Z9 28 U1 0 U2 2 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0039-128X J9 STEROIDS JI Steroids PD NOV PY 1994 VL 59 IS 11 BP 621 EP 627 DI 10.1016/0039-128X(94)90017-5 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA PR333 UT WOS:A1994PR33300002 PM 7701537 ER PT J AU HOWARD, G ANDERSON, R SORLIE, P ANDREWS, V BACKLUND, E BURKE, GL AF HOWARD, G ANDERSON, R SORLIE, P ANDREWS, V BACKLUND, E BURKE, GL TI ETHNIC-DIFFERENCES IN STROKE MORTALITY BETWEEN NON-HISPANIC WHITES, HISPANIC WHITES, AND BLACKS - THE NATIONAL LONGITUDINAL MORTALITY STUDY SO STROKE LA English DT Article DE CEREBROVASCULAR DISORDERS; MORTALITY; RACIAL DIFFERENCES ID UNITED-STATES; AMERICANS; DISEASE; DECLINE; TRENDS AB Background and Purpose Although US blacks are known to have an excess stroke mortality compared with US whites, little is known about the stroke burden of the Hispanic white population. This report will provide estimates of the relative burden of stroke mortality in the US black and Hispanic population relative to the white population and examine the consistency of this relation across age. Methods Data were from participants aged >45 years from the National Longitudinal Mortality Study. There were 1844 stroke deaths among 239 734 non-Hispanic whites, 46 deaths among 12 527 Hispanic whites, and 234 deaths among 23 468 black participants. Standard statistical methods were used to examine the ethnic differences in stroke mortality. Results The hazard ratios for black men and women (relative to non-Hispanic whites) were nearly identical, at >4.0 at age 45 but marginally <1.0 by age 85. For both Hispanic men and women, the hazard ratios (relative to non-Hispanic whites) were approximately 1.0 at age 45 but were marginally significantly <1.0 at older ages. The ethnic differences in stroke death rates reveal differences in age distributions of age at fatal stroke between these groups. Approximately 6% of fatal strokes for non-Hispanic whites occurred before age 60, whereas >15% occurred in both Hispanic whites and blacks. Conclusions These results suggest that (1) for Hispanics, stroke risk is similar to that for non-Hispanic whites at young ages but is marginally lower at older ages, (2) the excess stroke mortality in blacks mainly occurs at younger ages (between 45 and 55 years), and (3) the relation between stroke risk for blacks and Hispanics relative to whites is similar by sex. The impact of age on relative stroke mortality would argue against simple age adjustment for describing ethnic differences in stroke mortality. Finally, proportionally, more strokes occur at older ages in non-Hispanic whites than in either US blacks or Hispanic whites. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT NEUROL,WINSTON SALEM,NC 27157. NHLBI,BETHESDA,MD. US BUR CENSUS,SUITLAND,MD. RP HOWARD, G (reprint author), WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,MED CTR BLVD,WINSTON SALEM,NC 27157, USA. NR 33 TC 112 Z9 112 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 1994 VL 25 IS 11 BP 2120 EP 2125 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA PN942 UT WOS:A1994PN94200002 PM 7974531 ER PT J AU WALMSLEY, E METZGER, C DELANEY, JK FLETCHER, C AF WALMSLEY, E METZGER, C DELANEY, JK FLETCHER, C TI IMPROVED VISUALIZATION OF UNDERDRAWINGS WITH SOLID-STATE DETECTORS OPERATING IN THE INFRARED SO STUDIES IN CONSERVATION LA English DT Article C1 UNIV ARIZONA, DEPT CHEM & OPT SCI CTR, ATKINSON LAB, TUCSON, AZ 85721 USA. NCI, MAMMALIAN GENET LAB, FREDERICK, MD 21702 USA. RP NATL GALLERY ART, DEPT PAINTING CONSERVAT, WASHINGTON, DC 20565 USA. NR 24 TC 38 Z9 38 U1 0 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0039-3630 EI 2047-0584 J9 STUD CONSERV JI Stud. Conserv. PD NOV PY 1994 VL 39 IS 4 BP 217 EP 231 DI 10.2307/1506581 PG 15 WC Archaeology; Art; Chemistry, Applied; Chemistry, Analytical; Spectroscopy SC Archaeology; Art; Chemistry; Spectroscopy GA QD599 UT WOS:A1994QD59900001 ER PT J AU EGAN, MF HURD, Y HYDE, TM WEINBERGER, DR WYATT, RJ KLEINMAN, JE AF EGAN, MF HURD, Y HYDE, TM WEINBERGER, DR WYATT, RJ KLEINMAN, JE TI ALTERATIONS IN MESSENGER-RNA LEVELS OF D2 RECEPTORS AND NEUROPEPTIDES IN STRIATONIGRAL AND STRIATOPALLIDAL NEURONS OF RATS WITH NEUROLEPTIC-INDUCED DYSKINESIAS SO SYNAPSE LA English DT Article DE ENKEPHALIN; DYNORPHIN; SUBSTANCE P; HALOPERIDOL; STRIATUM; TARDIVE DYSKINESIA ID GLUTAMIC-ACID DECARBOXYLASE; PROENKEPHALIN MESSENGER-RNA; INSITU HYBRIDIZATION HISTOCHEMISTRY; SUBSTANTIA NIGRA LESIONS; VACUOUS JAW MOVEMENTS; BASAL GANGLIA; DOPAMINERGIC REGULATION; TARDIVE-DYSKINESIA; NUCLEUS-ACCUMBENS; GENE-EXPRESSION AB Chronic neuroleptic treatment in rat produces vacuous chewing movements (VCMs), analogous to TD in humans. We hypothesized that these hyperkinetic movements were due to alterations in striatonigral and striatopallidal GABAergic spiny II neurons. Rats were treated for 36 weeks with haloperidol decanoate and withdrawn for 28 weeks. Striatonigral and striatopallidal neurons were assessed using in situ hybridization histochemistry for mRNA levels of D1 and D2 dopamine receptors, preproenkephalin (ENK), prodynorphin (DYN), protachykinin (substance P), and glutamate decarboxylase (GAD67) in the dorsolateral and ventromedial striatum as well as the nucleus accumbens. Rats that did not develop VCMs (-VCM) had increased D2 receptor and DYN mRNA, and reduced substance P mRNA in the dorsolateral striatum. Rats with persistent VCMs (+VCM) had increased D2 receptor, ENK, and DYN mRNA in both striatal regions, and increased ENK and DYN mRNA in the nucleus accumbens, compared with controls. Relative to -VCM rats, however, +VCM rats only had increased ENK mRNA in the nucleus accumbens. Considering the overall pattern of mRNA changes, the data suggest that alterations in both the D1-mediated striatonigral and the D2-mediated striatopallidal pathways play a role in the expression of the VCM syndrome. To the extent that gene expression parallels changes in neuronal activity, this implies that the VCM syndrome is associated with increased activity in both pathways. (C) 1994 Wiley-Liss, Inc. C1 ST ELIZABETH HOSP,NIMH,CTR RES NEUROSCI,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. RP EGAN, MF (reprint author), ST ELIZABETH HOSP,NIMH,CTR RES NEUROSCI,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032, USA. NR 88 TC 78 Z9 79 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 0887-4476 J9 SYNAPSE JI Synapse PD NOV PY 1994 VL 18 IS 3 BP 178 EP 189 DI 10.1002/syn.890180303 PG 12 WC Neurosciences SC Neurosciences & Neurology GA QH209 UT WOS:A1994QH20900002 PM 7531873 ER PT J AU EDWARDS, MW GARRAFFO, HM DALY, JW AF EDWARDS, MW GARRAFFO, HM DALY, JW TI FACILE SYNTHESIS OF 4-PIPERIDONES BY CONDENSATION OF AN ALPHA,BETA-UNSATURATED KETONE, AN ALDEHYDE AND AMMONIA - SYNTHESIS OF THE DENDROBATID FROG ALKALOID 241D SO SYNTHESIS-STUTTGART LA English DT Article ID ION CHANNEL; ACETYLCHOLINE-RECEPTOR; PIPERIDINE-DERIVATIVES; HISTRIONICOTOXINS; PERHYDROHISTRIONICOTOXIN; COMPLEX; VENOM AB A one-step reaction of an alpha,beta-unsaturated ketone (3-penten-2-one, 1), an aldehyde (decanal, 2) and an amine (ammonia) afforded mainly the cis-isomer of(+/-)-2-methyl-6-nonyl-4-piperidone (3). Sodium borohydride reduction afforded as the major product (+/-)-cis,cis-4-hydroxy-2-methyl-6-nonylpiperidine (4), identical in NMR and IR spectra to the (+)-piperidine 241D isolated from skin extracts of a dendrobatid frog. The reaction was shown to be generally applicable for the synthesis of 2,6-disubstituted 4-piperidones. RP EDWARDS, MW (reprint author), NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892, USA. NR 25 TC 23 Z9 23 U1 0 U2 4 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0039-7881 J9 SYNTHESIS-STUTTGART JI Synthesis PD NOV PY 1994 IS 11 BP 1167 EP 1170 PG 4 WC Chemistry, Organic SC Chemistry GA PT608 UT WOS:A1994PT60800019 ER PT J AU TANNENBAUM, SH CHAO, ES GRALNICK, HR AF TANNENBAUM, SH CHAO, ES GRALNICK, HR TI HEPARIN ENHANCES ENDOTHELIAL-CELL VON-WILLEBRAND-FACTOR CONTENT BY GROWTH-FACTOR DEPENDENT MECHANISMS SO THROMBOSIS AND HAEMOSTASIS LA English DT Article ID WEIBEL-PALADE BODIES; VONWILLEBRAND-FACTOR; FACTOR-VIII; PROTEOLYTIC DEGRADATION; GAMMA-INTERFERON; MOLECULAR-WEIGHT; SECRETION; PROTEIN; BIOSYNTHESIS; DISEASE AB Von Willebrand factor (vWf), a multimeric adhesive glycoprotein synthesized, stored, and secreted in megakaryocytes and endothelial cells, is normally found in plasma, platelets and subendothelium. While many substances mediate the release of vWf from endothelial cells, factors that enhance vWf synthesis and partitioning to its regulated pathway are currently unknown. We studied the effect of pharmacologic doses of heparin on the vWf content of endothelial cells. After a lag of 8 h and in the presence of crude or purified growth factor, heparin al doses between 0.25 and 2 U (1.4-11 mu g)/ml, increased the content of high moleculr weight vWf. The increased amounts of vWf were localized to Weibel-Palade bodies and extracellular matrix. Lower molecular weight highly sulfated heparin or heparin-like compounds were most active in growth factor dependent endothelial cell vWf expression. There was no clear importance of polysaccharide sequence or protein core. RP TANNENBAUM, SH (reprint author), NIH,CTR CLIN,SERV HEMATOL,BLDG 10,ROOM 2C390,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 53 TC 4 Z9 4 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD NOV PY 1994 VL 72 IS 5 BP 770 EP 776 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA PR345 UT WOS:A1994PR34500021 PM 7900084 ER PT J AU HOLLADAY, SD COMMENT, CE KWON, J LUSTER, MI AF HOLLADAY, SD COMMENT, CE KWON, J LUSTER, MI TI FETAL HEMATOPOIETIC ALTERATIONS AFTER MATERNAL EXPOSURE TO ETHYLENE-GLYCOL MONOMETHYL ETHER - PROLYMPHOID CELL TARGETING SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID THYMIC ATROPHY; DIOXIN TCDD; TOXICITY; MOUSE; MICE; 2-METHOXYETHANOL; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; MATURATION; EXPRESSION; METABOLITE AB Ethylene glycol monomethyl ether (EGME), which is extensively used in the chemical industries, has been associated with hematologic disorders in both humans and experimental animals. EGME is metabolized to the active compound methoxyacetic acid (MAA), which readily crosses the placenta and impairs fetal development. However, little is known about the effect of maternal EGME exposure on the development of fetal immunity. In the present report, in utero treatment with EGME was found to alter expression of murine thymocyte and liver fetal cell-surface markers. Pregnant mice were exposed to 100, 150, or 200 mg/kg EGME from gestational days (gd) 10 to 17 and offspring examined on gd 18. Significant thymic atrophy and cellular depletion were found in EGME-exposed fetal mice. Flow cytometric analysis indicated that EGME treatment resulted in decreased percentages of CD4(+)8(+) thymocytes and increased percentages of CD4(-)8(-) thymocytes. In vitro exposure to MAA did not result in decreased thymocyte viability or proliferation. These data suggest that EGME, in addition to producing thymic hypocellularity, may inhibit thymocyte maturation. EGME also reduced the percentage of CD45(+) leukocytic cells present in fetal liver, an alteration that appeared to be largely manifested by decreased numbers of CD45R(+) and CD44(dim) prolymphoid cells. In vitro MAA exposure of fetal liver cells enriched for lymphoid precursors resulted in significant inhibition of proliferation. Reconstitution of irradiated hosts with gd 18 fetal liver cells from vehicle and EGME-exposed syngeneic donors demonstrated impaired ability of the EGME-treated fetal liver to repopulate the host spleen with B or T lymphocytes. These data suggest that EGME-induced immunosuppression may result from targeting of multiple hematopoietic compartments. Further, the present data indicate that fetal liver prolymphocytes may represent sensitive targets of EGME exposure. (C) 1994 Academic Press, Inc. C1 NIEHS,ENVIRONM IMMUNOL & NEUROBIOL SECT,RES TRIANGLE PK,NC 27709. RP HOLLADAY, SD (reprint author), VIRGINIA POLYTECH INST & STATE UNIV,VIRGINIA MARYLAND REG COLL VET MED,DEPT BIOMED SCI,BLACKSBURG,VA 24061, USA. NR 45 TC 14 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV PY 1994 VL 129 IS 1 BP 53 EP 60 DI 10.1006/taap.1994.1228 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA PQ822 UT WOS:A1994PQ82200007 PM 7974496 ER PT J AU CORLEY, RA BORMETT, GA GHANAYEM, BI AF CORLEY, RA BORMETT, GA GHANAYEM, BI TI PHYSIOLOGICALLY-BASED PHARMACOKINETICS OF 2-BUTOXYETHANOL AND ITS MAJOR METABOLITE, 2-BUTOXYACETIC ACID, IN RATS AND HUMANS SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID GLYCOL MONOBUTYL ETHER; PERCUTANEOUS-ABSORPTION; BUTOXYACETIC ACID; INHALED 2-BUTOXYETHANOL; HEMOLYTIC-ACTIVITY; DERMAL ABSORPTION; CHEMICAL VAPORS; F344 RATS; DISPOSITION; MODEL AB A physiologically based pharmacokinetic model was developed to describe the disposition of 2-butoxyethanol (CAS 111-76-2) and its major metabolite, 2-butoxyacetic acid, in rats and humans. A previous human inhalation model by Johanson (Toxicol. Lett. 34, 23 (1986)) was expanded to include additional routes of exposure, physiological descriptions for rats, competing pathways for metabolism of 2-butoxyethanol, and measured partition coefficients for 2-butoxyethanol and 2-butoxyacetic acid. Simulations were compared to data gathered from rats following either intravenous infusion or oral or inhalation exposure and from humans following either inhalation or dermal exposure to 2-butoxyethanol. It was necessary to add equations for both protein binding of 2-butoxyacetic acid in blood and saturable elimination of 2-butoxyacetic acid by the kidneys to consistently describe the data. While the model predicted that rats metabolize 2-butoxyethanol and eliminate the acid metabolite faster per kilogram body weight than humans, the balance of these two processes in addition to physiological differences between species resulted in higher predicted peak blood concentrations as well as total areas under the blood concentration time curves for 2-butoxyacetic acid for rats versus humans. These species differences in kinetics coupled with the fact that human blood is significantly less susceptible than rat blood to the hemolytic effects of 2-butoxyacetic acid indicate that there is considerably less risk for hemolysis in humans as a result of exposure to 2-butoxyethanol than would have been predicted solely from standard toxicity studies with rats. (C) 1994 Academic Press, Inc. C1 NIEHS,BIOCHEM RISK ANAL LAB,RES TRIANGLE PK,NC 27709. RP CORLEY, RA (reprint author), DOW CHEM CO USA,TOXICOL RES LAB,1803 BLDG,MIDLAND,MI 48674, USA. NR 59 TC 52 Z9 54 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV PY 1994 VL 129 IS 1 BP 61 EP 79 DI 10.1006/taap.1994.1229 PG 19 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA PQ822 UT WOS:A1994PQ82200008 PM 7974497 ER PT J AU LENFANT, C AF LENFANT, C TI NHLBI RESEARCH TRAINING AND CAREER-DEVELOPMENT PROGRAMS SO TRANSFUSION LA English DT Editorial Material RP LENFANT, C (reprint author), NHLBI,BLDG 31,ROOM 5A52,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD NOV-DEC PY 1994 VL 34 IS 11 BP 999 EP 1001 DI 10.1046/j.1537-2995.1994.341195065040.x PG 3 WC Hematology SC Hematology GA PU136 UT WOS:A1994PU13600012 PM 7974710 ER PT J AU PALEYANDA, RK ZHANG, DW HENNIGHAUSEN, L MCKNIGHT, RA LUBON, H AF PALEYANDA, RK ZHANG, DW HENNIGHAUSEN, L MCKNIGHT, RA LUBON, H TI REGULATION OF HUMAN PROTEIN-C GENE-EXPRESSION BY THE MOUSE WAP PROMOTER SO TRANSGENIC RESEARCH LA English DT Article DE WHEY ACIDIC PROTEIN GENE PROMOTER; RECOMBINANT HUMAN PROTEIN C; MOUSE MAMMARY GLAND; ALVEOLAR CELL MORPHOLOGY ID WHEY ACIDIC PROTEIN; HIGH-LEVEL EXPRESSION; TRANSGENIC MICE; NUCLEOTIDE-SEQUENCE; MAMMARY DEVELOPMENT; BETA-LACTOGLOBULIN; MILK; RAT; DIRECTS; REGION AB A 4.1 kb mouse whey acidic protein (mWAP) promoter was cloned from a C57BL/6 cosmid library. The tissue-specific and developmental pattern of expression of a hybrid gene comprised of the mWAP promoter fragment and the human protein C (HPC) gene was analysed in transgenic mice. The corresponding RNA was detected mainly in the mammary gland, with 'leakage' of expression in the salivary gland and kidney. The developmental pattern of transgene expression differed from that of the endogenous WAP gene. In particular, recombinant HPC (rHPC) transcripts were detected earlier in pregnancy than WAP RNA, with no significant increase during lactation. This indicates that regulatory elements responsible for developmental regulation are located outside the 4.1 kb mWAP gene promoter fragment, or if present, may be subject to position effects. Precocious expression of the transgene did not compromise the health or nursing abilities of transgenic females. Expression of rHPC affected the appearance of the mammary alveoli and alveolar epithelial cells in lactating transgenic mice. The alveoli were less distended and alveolar epithelial cells appeared cuboidal with centrally positioned nuclei. We suggest that the inefficient intracellular processing of rHPC can alter the histological appearance of alveolar epithelial cells in the transgenic mammary gland. C1 AMER RED CROSS,JEROME H HOLLAND LAB,ROCKVILLE,MD 20855. NIH,BIOCHEM & METAB LAB,BETHESDA,MD 20892. NR 34 TC 28 Z9 29 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0962-8819 J9 TRANSGENIC RES JI Transgenic Res. PD NOV PY 1994 VL 3 IS 6 BP 335 EP 343 DI 10.1007/BF01976765 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA PT052 UT WOS:A1994PT05200001 PM 8000430 ER PT J AU PINKERT, CA GALBREATH, EJ YANG, CW STRIKER, LJ AF PINKERT, CA GALBREATH, EJ YANG, CW STRIKER, LJ TI LIVER, RENAL AND SUBCUTANEOUS HISTOPATHOLOGY IN PEPCK-BGH TRANSGENIC PIGS SO TRANSGENIC RESEARCH LA English DT Note DE GENE TRANSFER; TRANSGENIC; SWINE; GROWTH HORMONE; PEPCK-BGH ID BOVINE GROWTH-HORMONE; DIETARY-REGULATION; GROWING PIGS; FUSION GENES; FACTOR-I; MICE; EXPRESSION; SOMATOTROPIN; LIVESTOCK; DEVELOP AB Transgenic pigs were created that harboured a phospho enolpyruvate carboxykinase-bovine growth hormone construct (PEPCK-bGH). Four founder animals and two transgenic offspring from one line were evaluated between 61/2 and 12 months of age. There was no evidence of severe hepatic or renal lesions in these pigs, which characterised transgenic PEPCK-bGH mice previously described. While glomerular and tubular lesions in kidney sections were not identified in the transgenic pigs, mesangial cell proliferation was observed in two transgenic offspring from a single line. Additionally, glomerular size was significantly increased in four of four puberal transgenic swine when compared to age- and sex-matched controls (28.30 +/- 4.1 vs. 14.2 +/- 2.7 X 10(5) mu m(3); representing 3 transgenic lines, p < 0.05). Surprisingly, no mature adipocytes were observed in subcutaneous sections obtained in transgenic GH pigs. Histological evaluation of these transgenic pigs further illustrates the requirement for precise control of growth-related genes and their protein products. C1 UNIV WISCONSIN,SCH VET MED,MADISON,WI 53706. NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. RP PINKERT, CA (reprint author), UNIV ALABAMA,DEPT COMPARAT MED,BIRMINGHAM,AL 35294, USA. OI Pinkert, Carl/0000-0001-7460-3881 NR 21 TC 13 Z9 13 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0962-8819 J9 TRANSGENIC RES JI Transgenic Res. PD NOV PY 1994 VL 3 IS 6 BP 401 EP 405 DI 10.1007/BF01976771 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA PT052 UT WOS:A1994PT05200007 PM 8000435 ER PT J AU QUON, MJ BUTTE, AJ TAYLOR, SI AF QUON, MJ BUTTE, AJ TAYLOR, SI TI INSULIN SIGNAL-TRANSDUCTION PATHWAYS SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID GUANINE-NUCLEOTIDE EXCHANGE; GTPASE-ACTIVATING PROTEIN; RECEPTOR TYROSINE KINASES; SH3 DOMAINS; PHOSPHATIDYLINOSITOL 3-KINASE; DEPENDENT ACTIVATION; ADAPTER PROTEIN; RAS; GRB2; PHOSPHORYLATION AB Insulin initiates its pleiotropic effects by activating the insulin receptor tyrosine kinase to phosphorylate several intracellular proteins. Recent studies have demonstrated that phosphotyrosine residues bind specifically to proteins that contain src homology 2 (SH2) domains, and that this interaction mediates the regulation of multiple intracellular signaling pathways. This article reviews recent progress in elucidating the detailed pathways that lead from the insulin receptor to the ultimate biologic actions of insulin. RP QUON, MJ (reprint author), NIDDK,DIABET BRANCH,BETHESDA,MD 20892, USA. RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 67 TC 45 Z9 45 U1 1 U2 2 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD NOV PY 1994 VL 5 IS 9 BP 369 EP 376 DI 10.1016/1043-2760(94)90104-X PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PX534 UT WOS:A1994PX53400003 PM 18407232 ER PT J AU KLAR, AJS AF KLAR, AJS TI A MODEL FOR SPECIFICATION OF THE LEFT-RIGHT AXIS IN VERTEBRATES SO TRENDS IN GENETICS LA English DT Article ID LEFT-RIGHT ASYMMETRY; FISSION YEAST; DNA STRANDS; CELLS; HANDEDNESS; REVERSAL; MOUSE; ELEGANS; GENES AB The mechanisms that underlie the formation of the left-right embryonic axis in vertebrates are not known, The programmed pattern of cell-type change in fission yeast results from the inheritance of specific chromatids of the parental chromosome. Here, I address how such a model may explain left-right specification of the viscera in mice. The model proposes that DNA replication produces different chromatids, and that these specific chromatins of both homologs are nonrandomly segregated to daughter cells to specify the left-right axis of the embryo. Such a model presents a simple explanation of the interesting phenotype of the newly discovered insertional mutation inv in mice, which causes reversal of the left-right axis, proposing that it is caused by a chromosomal inversion. RP KLAR, AJS (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BASIC RES PROGRAM,EUKARYOT GENE EXPRESS LAB,DEV GENET SECT,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101] NR 23 TC 51 Z9 51 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD NOV PY 1994 VL 10 IS 11 BP 392 EP 396 DI 10.1016/0168-9525(94)90055-8 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA PP492 UT WOS:A1994PP49200006 PM 7809944 ER PT J AU COX, JH BULLER, RML BENNINK, JR YEWDELL, JW KARUPIAH, G AF COX, JH BULLER, RML BENNINK, JR YEWDELL, JW KARUPIAH, G TI EXPRESSION OF ADENOVIRUS E3/19K PROTEIN DOES NOT ALTER MOUSE MHC CLASS I-RESTRICTED RESPONSES TO VACCINIA VIRUS SO VIROLOGY LA English DT Article ID CELL-SURFACE EXPRESSION; ENDOPLASMIC-RETICULUM; ANTIGEN PRESENTATION; IMMUNE DEFENSES; LYMPHOCYTES-T; GLYCOPROTEIN; LYSIS; PATHOGENESIS; RECOGNITION; SPECIFICITY AB The adenovirus E3/19K glycoprotein forms a tight complex with most human and certain mouse MHC class I allomorphs, retaining them in the endoplasmic reticulum by virtue of its cytosolic carboxyl terminal amino acids. This prevents the presentation of viral antigens at the cell surface to class I-restricted cytotoxic T lymphocytes (CTL). In adenovirus infection of cotton rats, E3/19K appears to act as an anti-inflammatory and/or immunosuppressive factor. Further studies of the role of E3/19K in adenovirus pathogenesis have been hampered by the lack of sufficient knowledge concerning the immune system of the cotton rat and by the poor correlation between adenovirus infection in mice and humans. We therefore addressed the function of this adenovirus glycoprotein in virus pathogenesis by infecting B10.HTG (H-2K(d)D(b)) mice with a vaccinia virus (W) recombinant encoding E3/19K. The K-d and D-b allomorphs normally present W antigens to CTL and have high affinity for E3/19K. Infected mice were examined for the kinetics of virus replication in various tissues a nd the generation of natural killer (NK) cell and CTL responses. It was found that expression of E3/19K by vaccinia virus had no detectable effect on CTL responses, NK responses, or viral replication. These findings suggest that immune modulating proteins evolve to exploit unique circumstances of the host immune response to a given virus. (C) 1994 Academic Press, Inc. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. RI yewdell, jyewdell@nih.gov/A-1702-2012; Karupiah, Gunasegaran/J-4707-2013 NR 23 TC 15 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 1 PY 1994 VL 204 IS 2 BP 558 EP 562 DI 10.1006/viro.1994.1569 PG 5 WC Virology SC Virology GA PM741 UT WOS:A1994PM74100007 PM 7941322 ER PT J AU SARID, R CHAJUT, A GAK, E KIM, Y HIXSON, CV OROSZLAN, S TRONICK, SR GAZIT, A YANIV, A AF SARID, R CHAJUT, A GAK, E KIM, Y HIXSON, CV OROSZLAN, S TRONICK, SR GAZIT, A YANIV, A TI GENOME ORGANIZATION OF A BIOLOGICALLY-ACTIVE MOLECULAR CLONE OF THE LYMPHOPROLIFERATIVE DISEASE VIRUS OF TURKEYS SO VIROLOGY LA English DT Article ID ROUS-SARCOMA VIRUS; CELL LEUKEMIA-VIRUS; COMPLETE NUCLEOTIDE-SEQUENCE; PFIZER MONKEY VIRUS; AUG INITIATOR CODON; POINT MUTATIONS; GENE-EXPRESSION; C RETROVIRUS; DEOXYURIDINE TRIPHOSPHATASE; TRANSLATIONAL SUPPRESSION AB The lymphoproliferative disease retrovirus (LPDV) induces an acute, horizontally transmitted disease of turkeys that is often fatal. Although LPDV cannot be grown in cultured cells, it was possible to isolate molecular clones of biologically active integrated proviral genomes from spleens of infected turkeys. Based upon molecular hybridization and nucleotide sequence comparisons of its pol gene, LPDV was shown to represent a distinct group of avian retroviruses most closely related to avian sarcoma-leukemia viruses. Here we report the complete nucleotide sequence of the LPDV genome as well as amino acid sequence analysis of its gag gene products. The genetic organization of LPDV is characteristic of members of the oncovirus subfamily. Further sequence comparisons of the gag gene confirmed that LPDV is most closely related to Rous sarcoma virus (RSV). However, the gag, pro, and pol open reading frames (ORFs) were in different translational phases so that the expression of their mature gene products would require the double frame-shifting mechanism utilized by simian retroviruses, mouse mammary tumor virus, and human T-cell leukemia virus. In contrast, the RSV proteinase is synthesized as part of the gag precursor. The LPDV gag gene differs from that of RSV as well as from all other retroviruses in that it encodes a unique 31,000-Da (p31) protein, located between the MA and the CA coding sequences. Four short ORFs of unknown function were present. Whether the putative products of these ORFs account for the acute nature of LPDV-induced disease remains to be determined. C1 NCI, MOLEC & CELLULAR BIOL LAB, BETHESDA, MD 20892 USA. TEL AVIV UNIV, SACKLER SCH MED, DEPT HUMAN MICROBIOL, IL-69978 TEL AVIV, ISRAEL. NCI, FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM, MOLEC VIROL & CARCINOGENESIS LA, FREDERICK, MD 21702 USA. FU NCI NIH HHS [N01-CO-7410] NR 73 TC 5 Z9 5 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 1 PY 1994 VL 204 IS 2 BP 680 EP 691 DI 10.1006/viro.1994.1584 PG 12 WC Virology SC Virology GA PM741 UT WOS:A1994PM74100022 PM 7941337 ER PT J AU KALINSKI, H MASHIAH, P ROTEM, D ORZECH, Y SHERMAN, L MIKI, T YANIV, A GAZIT, A TRONICK, SR AF KALINSKI, H MASHIAH, P ROTEM, D ORZECH, Y SHERMAN, L MIKI, T YANIV, A GAZIT, A TRONICK, SR TI CHARACTERIZATION OF CDNAS SPECIES ENCODING THE TAT PROTEIN OF CAPRINE ARTHRITIS-ENCEPHALITIS VIRUS SO VIROLOGY LA English DT Note ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTIOUS-ANEMIA VIRUS; LONG TERMINAL REPEAT; NUCLEOTIDE-SEQUENCE ANALYSIS; REV-LIKE TRANSCRIPTS; VISNA VIRUS; HIV-1 TAT; GENE-EXPRESSION; MUTATIONAL ANALYSIS; INDEPENDENT ACTIVATION AB Two distinct species of caprine arthritis encephalitis virus (CAEV) tat cDNAs were isolated early after infection of a Himalayan tahr cell line. Sequence analyses predicted that one cDNA (pCEV/el) represented a polycistronic transcript that encodes Tat and Rev as well as an N-terminally truncated transmembrane protein and a protein, designated X, whose function is unknown; whereas the other cDNA (pCEV/f1) encodes Tat and the env gene products, pCEV/el trans-activated a CAEV LTR-chloramphenicol acetyltransferase reporter gene in goat synovial membrane cells. This activity was shown to be encoded by the Tat open reading frame by analysis of a deletion mutant. Because the pCAEV/f1 insert was unstable in plasmid form, its Tat activity could not be convincingly demonstrated. The target sequences for Tat within the CAEV LTR were localized to the Us region which, when placed in either orientation upstream of heterologous promoters, was able to confer responsiveness to Tat. (C) 1994 Academic Press, Inc. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. TEL AVIV UNIV,SACKLER SCH MED,DEPT HUMAN MICROBIOL,IL-69978 TEL AVIV,ISRAEL. NR 66 TC 15 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 1 PY 1994 VL 204 IS 2 BP 828 EP 834 DI 10.1006/viro.1994.1602 PG 7 WC Virology SC Virology GA PM741 UT WOS:A1994PM74100040 PM 7941354 ER PT J AU LYU, MS KOZAK, CA AF LYU, MS KOZAK, CA TI GENETIC-MAPPING OF THE AMPHOTROPIC MURINE LEUKEMIA-VIRUS RECEPTOR ON MOUSE CHROMOSOME-8 SO VIROLOGY LA English DT Note ID SUSCEPTIBILITY; CELLS; REPLICATION; INFECTION; LOCUS AB Southern blotting with a molecular clone of the amphotropic murine leukemia virus receptor identified restriction enzyme length polymorphisms among different taxonomic groups of mice. Analysis of the progeny of two interspecies genetic crosses was used to establish the genetic map location of the mouse gene encoding this receptor, Ram1, within the proximal region of chromosome 8. (C) 1994 Academic Press, Inc. C1 NIAID,BETHESDA,MD 20892. NR 18 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 1 PY 1994 VL 204 IS 2 BP 868 EP 869 DI 10.1006/viro.1994.1610 PG 2 WC Virology SC Virology GA PM741 UT WOS:A1994PM74100048 PM 7941361 ER PT J AU VERMUT, M WIDNER, WR DINMAN, JD WICKNER, RB AF VERMUT, M WIDNER, WR DINMAN, JD WICKNER, RB TI SEQUENCE OF MKT1, NEEDED FOR PROPAGATION OF M(2) SATELLITE DSRNA OF THE L-A VIRUS OF SACCHAROMYCES-CEREVISIAE SO YEAST LA English DT Note DE SACCHAROMYCES CEREVISIAE; MKT1; KILLER MAINTENANCE ID DOUBLE-STRANDED-RNA; YEAST; PROTEINS AB MKT1 is required for maintenance of K-2 above 30 degrees C in strains with the L-A-HN variant of the L-A double-stranded RNA virus of Saccharomyces cerevisiae. We report that MKT1 encodes a 92 979 Da protein with serine-rich regions and the retroviral protease signature, DTG, but with no substantial homology to proteins presently in the databases. This sequence is available from GenBank under Accession Number U09129. C1 NIDDKD,BIOCHEM PHARMACOL LAB,GENET SIMPLE EUKARYOTES SECT,BETHESDA,MD 20892. OI Dinman, Jonathan/0000-0002-2402-9698 NR 10 TC 4 Z9 5 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0749-503X J9 YEAST JI Yeast PD NOV PY 1994 VL 10 IS 11 BP 1477 EP 1479 DI 10.1002/yea.320101111 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA PT042 UT WOS:A1994PT04200009 PM 7532890 ER PT J AU KODAVANTI, PRS SHAFER, TJ WARD, TR MUNDY, WR FREUDENRICH, T HARRY, GJ TILSON, HA AF KODAVANTI, PRS SHAFER, TJ WARD, TR MUNDY, WR FREUDENRICH, T HARRY, GJ TILSON, HA TI DIFFERENTIAL-EFFECTS OF POLYCHLORINATED BIPHENYL CONGENERS ON PHOSPHOINOSITIDE HYDROLYSIS AND PROTEIN-KINASE-C TRANSLOCATION IN RAT CEREBELLAR GRANULE CELLS SO BRAIN RESEARCH LA English DT Article DE POLYCHLORINATED BIPHENYL CONGENER; PHOSPHOINOSITIDE HYDROLYSIS; [H-3] PHORBOL ESTER BINDING; CEREBELLAR GRANULE CELL ID INTRACELLULAR CALCIUM; MUSCARINIC RECEPTORS; GLUTAMATE RECEPTOR; PRIMARY CULTURES; NERVOUS-SYSTEM; AMINO-ACIDS; EXPOSURE; BINDING; NEURONS; BRAIN AB Previous reports from our laboratory have suggested that the neuroactivity of some polychlorinated biphenyl (PCB) congeners is associated with perturbations in cellular Ca2+-homeostasis. We have characterized further the neurochemical effects of PCBs on signal transduction in primary cultures of cerebellar granule cells. The present experiments found that neither 2,2'-dichlorobiphenyl (DCBP), an ortho-substituted congener, nor 3,3',4,4',5-pentachlorobiphenyl (PCBP), a non-ortho-substituted congener, affected basal phosphoinositide (PI) hydrolysis in cerebellar granule cells. However, at concentrations up to 50 mu M, DCBP potentiated carbachol-stimulated PI hydrolysis, while decreasing it at 100 mu M. PCBP, on the other hand, had no effect on carbachol-stimulated PI hydrolysis in concentrations up to 100 mu M. [H-3]Phorbol ester ([H-3]PDBu) binding was used to determine protein kinase C (PKC) translocation. DCBP increased [H-3]PDBu binding in a concentration-dependent manner and a twofold increase was observed at 100 mu M in cerebellar granule cells. PCBP had no effect on [H-3]PDBu binding at concentrations up to 100 mu M. The effect of DCBP on [H-3]PDBu binding was time-dependent and was also dependent on the presence of external Ca2+ in the medium. To test the hypothesis that DCBP increases [H-3]PDBu binding by acting on receptor-activated calcium channels, the effects of DCBP were compared to those of L-glutamate. The effects of DCBP (50 mu M) and glutamate (20 mu M) were additive. MK-801, a non-competitive NMDA antagonist, blocked the effects of glutamate, but had no effect on the DCBP-induced increase in [H-3]PDBu binding. Other pharmacological pretreatments such as incubations with 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; competitive NMDA antagonist), 6-cyano-7-nitro quinoxaline-2,3-dione (CNQX; AMPA antagonist), verapamil (Ca2+-channel antagonist) or tetrodotoxin (Na+ channel antagonist) also had no effect on DCBP-induced increases in [H-3]PDBu binding. These studies indicate that DCBP, a putative neuroactive PCB congener, has a biphasic effect on receptor-mediated PI hydrolysis and causes translocation of PKC in cerebellar granule cells. C1 MANTECH ENVIRONM TECHNOL INC,RES TRIANGLE PK,NC 27709. NIEHS,DIV INTRAMURAL RES,RES TRIANGLE PK,NC 27709. RP KODAVANTI, PRS (reprint author), US EPA,DIV NEUROTOXICOL,CELLULAR & MOLEC TOXICOL BRANCH,HLTH EFFECTS RES LAB,MD 74B,RES TRIANGLE PK,NC 27711, USA. RI Shafer, Timothy/D-6243-2013 NR 56 TC 85 Z9 86 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 31 PY 1994 VL 662 IS 1-2 BP 75 EP 82 DI 10.1016/0006-8993(94)90797-8 PG 8 WC Neurosciences SC Neurosciences & Neurology GA PP066 UT WOS:A1994PP06600008 PM 7859093 ER PT J AU WOLFE, MS ZATZ, M AF WOLFE, MS ZATZ, M TI SYNTHESIS OF HEAT-SHOCK PROTEINS IN CULTURED CHICK PINEAL CELLS SO BRAIN RESEARCH LA English DT Note DE CIRCADIAN RHYTHM; MELATONIN; PHOTOENTRAINMENT ID N-ACETYLTRANSFERASE ACTIVITY; INVITRO; STRESS; GLAND; LIGHT AB Chick pineal cells in static culture display a persistent, photosensitive, circadian rhythm of melatonin synthesis and release. Melatonin synthesis and its rhythm are also sensitive to temperature changes. By SDS-PAGE autoradiography, we found that several heat shock proteins (HSPs 25, 70, and 90) are synthesized under temperature conditions which also cause changes in melatonin production and rhythms. We did not see substantial phase-dependent differences in the induction of HSP synthesis, nor did we detect any clear effect of light on the synthesis of these proteins. C1 NIMH,CELL BIOL LAB,BIOCHEM PHARMACOL SECT,BETHESDA,MD 20892. NR 18 TC 4 Z9 4 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 31 PY 1994 VL 662 IS 1-2 BP 273 EP 277 DI 10.1016/0006-8993(94)90825-7 PG 5 WC Neurosciences SC Neurosciences & Neurology GA PP066 UT WOS:A1994PP06600036 PM 7859084 ER PT J AU ULANE, MM BUTLER, JD PERI, A MIELE, L ULANE, RE HUBBARD, VS AF ULANE, MM BUTLER, JD PERI, A MIELE, L ULANE, RE HUBBARD, VS TI CYSTIC-FIBROSIS AND PHOSPHATIDYLCHOLINE BIOSYNTHESIS SO CLINICA CHIMICA ACTA LA English DT Article DE CYSTIC FIBROSIS; PHOSPHATIDYLCHOLINE; CHOLINE; FATTY ACIDS; MEMBRANES ID GENE; IDENTIFICATION; PHOSPHOLIPIDS; TRANSPORT; CFTR; EXPRESSION; EPITHELIUM; MEMBRANES AB The cystic fibrosis (CF) gene defect may be associated with a defect in membrane recycling. We have investigated the metabolism of the main constituent of plasma membrane, phosphatidylcholine (PC). In this study of platelets and fibroblasts, we show an increased uptake of choline into PC of CF cells as compared with normal cells, No accumulation of PC was seen. Other patients with respiratory disease (not CF) showed normal rates of incorporation of choline into platelet PC. Platelets from heterozygote individuals showed intermediate turnover rates of choline incorporation into PC. The increase in choline incorporation into PC in CF platelets was not due to modified or increased sensitivity to either cAMP or prostaglandin E(2). The total amount and the proportions of the major phospholipids in platelets of control and CF individuals were identical. These findings indicate an increased turnover rate of this phospholipid in CF cells rather than an increased net synthesis. C1 NIDDKD,PEDIAT METAB BRANCH,BETHESDA,MD 20892. NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. NR 28 TC 24 Z9 24 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD OCT 31 PY 1994 VL 230 IS 2 BP 109 EP 116 DI 10.1016/0009-8981(94)90263-1 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA QA754 UT WOS:A1994QA75400001 PM 7834862 ER PT J AU UREN, A YU, JC GHOLAMI, NS PIERCE, JH HEIDARAN, MA AF UREN, A YU, JC GHOLAMI, NS PIERCE, JH HEIDARAN, MA TI THE ALPHA-PDGFR TYROSINE KINASE MEDIATES LOCOMOTION OF 2 DIFFERENT CELL-TYPES THROUGH CHEMOTAXIS AND CHEMOKINESIS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID GROWTH-FACTOR RECEPTORS; SIGNAL TRANSDUCTION; PATHWAYS; ESTABLISHES; EXPRESSION; ACTIVATION AB To determine the capability of alpha PDGFR to couple with chemotactic signaling, we established 32D cells expressing wild type alpha PDGFR (alpha RWT), a kinase-defective mutant of alpha PDGFR (alpha R627R), or wild type beta PDGFR (beta RWT). Using a modified Boyden chamber, we showed that PDGF induced significant cell migration of 32D cells expressing alpha RWT or beta RWT, but not of those expressing alpha R627R. Furthermore, the cell migration was largely reduced in each case when the same concentration of PDGF was present in both chambers, suggesting that cell migration observed in 32D expressing alpha RWT is mainly due to alpha PDGFR-mediated chemotaxis. Consistent with these results, PDGF-AA induced significant cell migration of NTH3T3 fibroblasts, which was markedly blocked by the presence of excess neutralizing polyclonal antibody to PDGF-AA. These results provide evidence that alpha PDGFR kinase activity is essential for mediating ligand-induced chemotactic and chemokinetic responses in two different cell types. (C) 1994 Academic Press, Inc. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 19 TC 22 Z9 22 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 OCT 28 PY 1994 VL 204 IS 2 BP 628 EP 634 DI 10.1006/bbrc.1994.2505 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PN634 UT WOS:A1994PN63400027 PM 7980524 ER PT J AU BIANCHI, S FABIANI, S MURATORI, M ARNOLD, A SAKAGUCHI, K MIKI, T BRANDI, ML AF BIANCHI, S FABIANI, S MURATORI, M ARNOLD, A SAKAGUCHI, K MIKI, T BRANDI, ML TI CALCIUM MODULATES THE CYCLIN D1 EXPRESSION IN A RAT PARATHYROID CELL-LINE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID RETINOBLASTOMA PROTEIN; GENE-EXPRESSION; G1; PHASE; FIBROBLASTS; CLONING; KINASE; G(1); ACTIVATION; INHIBITION AB We have used a rat epithelial parathyroid cell line (PT-r) to study the expression and regulation of D-type cyclins, In PT-r cells the cyclin D1 gene is the most abundantly expressed, being transcribed in at least two mRNAs whose levels oscillate during the cell cycle. We also screened a cDNA library prepared from PT-r cells with the human cyclin D1 probe and isolated its rat homologue. Cyclin D2 and D3 mRNAs are both represented in PT-r cells but the former one is only barely detectable. Moreover, the oscillation of cyclin D3 transcript is slightly delayed when compared to cyclin D1 and D2. Since extracellular calcium inhibits parathyroid cell proliferation, we looked for the effect of the ion on the expression of cyclin D genes in PT-r cells. Increasing amounts of calcium in the incubation medium reduced the expression of rat cyclin D1 and D2. The effect appears to be cell-specific and probably mediated through the inhibition of mitogenic signalling pathways. (C) 1994 Academic Press, Inc. C1 UNIV FLORENCE,DEPT CLIN PHYSIOPATHOL,ENDOCRINE UNIT,I-50139 FLORENCE,ITALY. MASSACHUSETTS GEN HOSP,ENDOCRINE ONCOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA55909]; NIDDK NIH HHS [DK11794] NR 34 TC 23 Z9 24 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 28 PY 1994 VL 204 IS 2 BP 691 EP 700 DI 10.1006/bbrc.1994.2515 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PN634 UT WOS:A1994PN63400037 PM 7980531 ER PT J AU RENGARAJAN, K DESMET, MD CHADER, GJ WIGGERT, B AF RENGARAJAN, K DESMET, MD CHADER, GJ WIGGERT, B TI CHARACTERIZATION OF HUMAN B-CELL PROTEINS BINDING SPECIFICALLY TO UVEITOPATHOGENIC PEPTIDE-1169-1191 OF BOVINE IRBP SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HEAT-SHOCK PROTEINS; NUCLEOTIDE-SEQUENCE; ACTIN; HSP70; IDENTIFICATION; PURIFICATION; EXPRESSION; FAMILY; COMMON; CDNA AB Peptide 1169-1191 is a major uveitopathogenic determinant of bovine Interphotoreceptor Retinoid Binding Protein (IRBP) in Lewis rats. Previously, we identified two proteins with approximate molecular masses of 72 and 74 kDa and one with a molecular mass of 40 kDa from B cells of naive Lewis rats and EBV-transformed B cells from a human patient with ocular Behcet's disease that bind to bovine IRBP peptide 1169-1191. In this study, we have partially characterized these proteins. The two proteins with molecular masses 72 and 74 kDa belong to the HSP 70 family of proteins and the 40-kDa protein is actin. (C) 1994 Academic Press, Inc. C1 NEI,IMMUNOL LAB,BETHESDA,MD 20892. RP RENGARAJAN, K (reprint author), NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892, USA. OI de Smet, Marc/0000-0002-9217-5603 NR 31 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 28 PY 1994 VL 204 IS 2 BP 799 EP 806 DI 10.1006/bbrc.1994.2530 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PN634 UT WOS:A1994PN63400052 PM 7980545 ER PT J AU LU, J NOTKINS, AL LAN, MS AF LU, J NOTKINS, AL LAN, MS TI ISOLATION, SEQUENCE AND EXPRESSION OF A NOVEL MOUSE-BRAIN CDNA, MIA-2, AND ITS RELATEDNESS TO MEMBERS OF THE PROTEIN-TYROSINE-PHOSPHATASE FAMILY SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CD45 PHOSPHOTYROSINE PHOSPHATASE; CATALYTIC DOMAINS; DROSOPHILA; KINASE; AXONS; LCA; LAR AB This study describes the isolation of a putative transmembrane protein tyrosine phosphatase (PTP), mIA-2, from a mouse brain cDNA library, The cDNA encodes 979 amino acids containing a unique extracellular domain and a single intracellular catalytic domain. Expression of mIA-2 was found primarily in the central nervous system and in neuroendocrine cells. The sequence shares a high degree of homology with its human counterpart (92% identity), especially in the intracellular domain, which shows 99.3% identity between the two species. In both human and mouse IA-2, several substitutions were found in the highly conserved regions including an Ala to Asp substitution in the core sequence. Bacterial expression of a glutathione S-transferase fusion protein showed that mIA-2 had no enzyme activity with conventional substrates such as Raytide, myelin basic protein, angiotensin, RR-src and pNpp. When tested with the total tyrosine-phosphorylated cellular proteins isolated on an anti-phosphotyrosine antibody column, it also showed little, if any, enzyme activity. These findings suggest that mIA-2 is a new member of the transmembrane PTP family that either has very narrow substrate specificity perhaps requiring post-translational modification for enzyme activity or has a still unknown biological function. RP LU, J (reprint author), NIDR,ORAL MED LAB,BETHESDA,MD 20892, USA. NR 21 TC 69 Z9 71 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 28 PY 1994 VL 204 IS 2 BP 930 EP 936 DI 10.1006/bbrc.1994.2549 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PN634 UT WOS:A1994PN63400071 PM 7980563 ER PT J AU BATCHU, RB KOTIN, RM HERMONAT, PL AF BATCHU, RB KOTIN, RM HERMONAT, PL TI THE REGULATORY REP PROTEIN OF ADENOASSOCIATED VIRUS BINDS TO SEQUENCES WITHIN THE C-H-RAS PROMOTER SO CANCER LETTERS LA English DT Article DE ADENOASSOCIATED VIRUS; REP; TRANSCRIPTION FACTOR; C-H-RAS; ANTIONCOGENE; DNA BINDING ID INHIBITS CELLULAR-TRANSFORMATION; HERPES-SIMPLEX VIRUS; ADENOASSOCIATED VIRUS; DNA-REPLICATION; GENE-EXPRESSION; BOVINE PAPILLOMAVIRUS; SATELLITE VIRUS; HAMSTER-CELLS; TYPE-2; INTEGRATION AB The large rep gene products (rep68 and rep78) of adeno-associated virus (AAV) are pleiotropic effector proteins which not only play a critical role in AAV DNA replication and in the trans-regulation of AAV promotor elements, but are also known for their once-suppressive functions. We have previously demonstrated that the large AAV rep protein will strongly inhibit expression from the c-H-ras promoter, but not the murine osteosarcoma virus long terminal repeat (MSV-LTR) promoter. To investigate the possibility that rep may physically bind to these promoter sequences, specifically to GCTC motifs, we conducted electrophoretic mobility shift assays (EMSA) with a maltose binding protein-rep chimeric protein, MBP-rep68 Delta, and synthetic double stranded DNA substrates of sequences selected from the c-H-ras and MSV-LTR promoters, as well as with the AAV TR. We find that MPB-rep68 Delta bound the AAV TR DNA sequence (three motifs) most strongly, followed by the selected c-H-ras DNA sequence (two noninterfering motifs), and most poorly to the MSV-LTR DNA (one motif). These data are consistent with our previous study and suggest a direct mechanism of action for AAV rep inhibition of the c-H-ras promoter. Furthermore, the re suits suggest that the number of GCTC motifs, when closely associated, affect the affinity of rep binding. Finally, we find that MBP-rep68 Delta also binds to the c-H-ras oligomer substrates which have secondary hairpin structures. C1 UNIV ARKANSAS MED SCI HOSP,DEPT OBSTET & GYNECOL,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT MICROBIOL & IMMUNOL,LITTLE ROCK,AR 72205. GENET THERAPY INC,GAITHERSBURG,MD 20878. NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892. RI kotin, robert/B-8954-2008 FU NCI NIH HHS [CA55051] NR 45 TC 27 Z9 27 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD OCT 28 PY 1994 VL 86 IS 1 BP 23 EP 31 DI 10.1016/0304-3835(94)90176-7 PG 9 WC Oncology SC Oncology GA PQ845 UT WOS:A1994PQ84500004 PM 7954351 ER PT J AU SCHLICHTING, I YANG, XJ MILES, EW KIM, AY ANDERSON, KS AF SCHLICHTING, I YANG, XJ MILES, EW KIM, AY ANDERSON, KS TI STRUCTURAL AND KINETIC-ANALYSIS OF A CHANNEL-IMPAIRED MUTANT OF TRYPTOPHAN SYNTHASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID SALMONELLA-TYPHIMURIUM; MECHANISM AB Substrate channeling is a process by which two sequential enzymes interact to transfer a metabolite (or intermediate) from one enzyme active site to the next without allowing free diffusion of the metabolite. Channeling is thought to play an important role in metabolic regulation and cellular modulation of enzymatic activities. Although there are numerous examples of sequential enzyme pairs in glycolysis and other biosynthetic pathways that are thought to exhibit channeling, this is as yet controversial. Tryptophan synthase is considered the best example for an enzyme displaying channeling behavior between subunits. Tryptophan synthase is an alpha(2) beta(2) tetrameric enzyme complex, which catalyzes the last two steps in the biosynthesis of L-tryptophan. The alpha subunit catalyzes the cleavage of indole-3-glycerol phosphate to indole and glyceraldehyde-3-phosphate; the beta subunit catalyzes the condensation of indole with serine to form tryptophan, in a reaction mediated by pyridoxal phosphate. The inability to trap free indole in the steady-state reaction and analysis of the kinetics of single turnover reactions have led to the postulate that indole may pass directly from the alpha to the beta site without diffusion through solution (Demoss, J. A. (1962) Biochim. Biophys. Acta 62, 279-293; Matchett, W. M. (1974) J. Biol. Chem. 249, 4041-4049). The crystal structure of tryptophan synthase from Salmonella typhimurium has provided additional support for substrate channeling by elucidating a 25-Angstrom hydrophobic tunnel connecting the two catalytic sites (Hyde, C. C., Ahmed, S. A., Padlan, E. A., Miles, E. W., and Davies, D. R. (1988) J. Biol. Chem. 263, 17857-17871). The structure suggests that mutation of a residue lining the tunnel to a more bulky residue might impede or block the passage of indole during catalysis thus enabling detection of indole during a single enzyme turnover. A mutant of tryptophan synthase has been prepared in which one of the residues lining the tunnel, beta Cys-170, has been replaced with a bulkier tryptophan residue. Kinetic and structural analyses of the beta C170W mutant by rapid chemical quench methods and x-ray crystallographic analysis show both the transient formation of indole and the obstruction of the tunnel, thus providing direct evidence for the substrate channeling mechanism. C1 YALE UNIV,SCH MED,DEPT PHARMACOL,NEW HAVEN,CT 06510. MAX PLANCK INST MED RES,BIOPHYS ABT,D-69120 HEIDELBERG,GERMANY. NIH,BETHESDA,MD 20892. RI Schlichting, Ilme/I-1339-2013 FU NIGMS NIH HHS [GM45343] NR 11 TC 23 Z9 23 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 28 PY 1994 VL 269 IS 43 BP 26591 EP 26593 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ931 UT WOS:A1994PQ93100001 PM 7929385 ER PT J AU WOODFORD, KJ HOWELL, RM USDIN, K AF WOODFORD, KJ HOWELL, RM USDIN, K TI A NOVEL K+-DEPENDENT DNA-SYNTHESIS ARREST SITE IN A COMMONLY OCCURRING SEQUENCE MOTIF IN EUKARYOTES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-GLOBIN GENE; REVERSE-TRANSCRIPTASE; REPLICATION INVITRO; INTERNAL REGIONS; POLYMERASE-ALPHA; STRAND TRANSFER; INSULIN GENE; AMPLIFICATION; COMPONENTS; TEMPLATES AB We have found that a strong DNA synthesis arrest site forms in the chicken beta-globin promoter in vitro under physiological conditions. The arrest site is located in a G + C-rich region in which the guanines are located predominately on the top strand and the pyrimidines on the bottom strand. This region is non-palindromic and has no mirror symmetry. Arrest of DNA synthesis is only observed when the G-rich strand of the promoter is used as the template, and shows an absolute requirement for K+. The sequence G(16)CG(GGT)(3) is necessary and sufficient to arrest DNA synthesis. This arrest is template concentration independent and is eliminated by blocking the N7 positions of the last 4 guanine residues in the arrest site. These observations suggest that the basis of the block to chain extension is the formation of an unusual tetraplex-like structure by the template strand. Sequences able to form intrastrand tetraplexes are ubiquitous in eukaryotes. We show that known intrastrand tetraplex-forming sequences arrest DNA synthesis in vitro, suggesting that this may be a general property of DNA tetraplexes. We suggest that the arrest of DNA synthesis by some of these structures may account for some of the high frequency of recombination associated with these loci, perhaps by promoting strand slippage or providing an opportunity for strand exchange. C1 NIDDKD,GENOM STRUCT & FUNCT SECT,BETHESDA,MD 20892. NR 39 TC 70 Z9 71 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 28 PY 1994 VL 269 IS 43 BP 27029 EP 27035 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ931 UT WOS:A1994PQ93100067 PM 7929444 ER PT J AU SCHMIDT, BF HERNANDEZ, L ROUZER, C CZERWINSKI, G CHMURNY, G MICHEJDA, CJ AF SCHMIDT, BF HERNANDEZ, L ROUZER, C CZERWINSKI, G CHMURNY, G MICHEJDA, CJ TI PEPTIDE-LINKED 1,3-DIALKYL-3-ACYLTRIAZENES - GASTRIN RECEPTOR DIRECTED ANTINEOPLASTIC ALKYLATING-AGENTS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HUMAN-COLON CARCINOMA; CYTO-TOXIC AGENTS; CANCER-CELLS; GASTROINTESTINAL HORMONES; ENDOGENOUS GASTRIN; INVITRO GROWTH; BREAST-CANCER; LINES; TRIALKYLTRIAZENES; CHOLECYSTOKININ AB The gastrin receptor is expressed in various human cancers, such as the adenocarcinoma of the colon. The peptide hormone gastrin and the C-terminal peptides derived from it act as growth factors for these cancers. The hypothesis for the present work was to use the gastrin receptor as a target for appropriately constructed cytotoxic agents. We developed methods to link tetragastrin and pentagastrin by their N-termini to cytotoxic 1-(2-chloroethyl)-3-benzyl-3-succinoyltriazene. These compounds, CBS-4 and CBS-5, respectively, whose complete structures were determined by multinuclear NMR and mass spectrometry, competed effectively with gastrin in an assay using either guinea pig stomach fundus or the rat acinar tumor cell line AR42J as the source of the receptor. CBS-5 was cytotoxic to AR42J cells but was not toxic to A549 human lung cancer cells, which do not express the receptor. C1 NCI,FREDERICK CANC RES & DEV CTR,MOLEC ASPECTS DRUG DESIGN SECT,MSL,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 50 TC 14 Z9 14 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 OCT 28 PY 1994 VL 37 IS 22 BP 3812 EP 3818 DI 10.1021/jm00048a016 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA PP889 UT WOS:A1994PP88900016 PM 7966139 ER PT J AU TANTILLO, C DING, JP JACOBOMOLINA, A NANNI, RG BOYER, PL HUGHES, SH PAUWELS, R ANDRIES, K JANSSEN, PAJ ARNOLD, E AF TANTILLO, C DING, JP JACOBOMOLINA, A NANNI, RG BOYER, PL HUGHES, SH PAUWELS, R ANDRIES, K JANSSEN, PAJ ARNOLD, E TI LOCATIONS OF ANTI-AIDS DRUG-BINDING SITES AND RESISTANCE MUTATIONS IN THE 3-DIMENSIONAL STRUCTURE OF HIV-1 REVERSE-TRANSCRIPTASE - IMPLICATIONS FOR MECHANISMS OF DRUG-INHIBITION AND RESISTANCE SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Review DE REVERSE TRANSCRIPTASE; NONNUCLEOSIDE INHIBITOR; DRUG RESISTANCE; STRUCTURE-BASED DRUG DESIGN; NUCLEOSIDE ANALOG INHIBITOR ID HUMAN-IMMUNODEFICIENCY-VIRUS; AMINO-ACID SUBSTITUTIONS; HIGH-LEVEL RESISTANCE; NONNUCLEOSIDE INHIBITORS; TYPE-1 HIV-1; PYRIDINONE DERIVATIVES; ANGSTROM RESOLUTION; REDUCED SENSITIVITY; CRYSTAL-STRUCTURE; TIBO DERIVATIVES AB The locations of HIV-1 RT nucleoside and non-nucleoside inhibitor-binding sites and inhibitor-resistance mutations are analyzed in the context of the three-dimensional structure of the enzyme and implications for mechanisms of drug inhibition and resistance are discussed. In order to help identify residues that may play a role in inhibitor binding, solvent accessibilities of amino acids that comprise the inhibitor-binding sites in the structure of HIV-1 RT complexed with a dsDNA template-primer are analyzed. While some mutations that cause resistance to nucleoside analogs, such as AZT, ddI, and ddC, are located near enough to the dNTP-binding site to directly interfere with binding of nucleoside analogs, many are located away from the dNTP-binding site and more likely confer resistance by other mechanisms. Many of the latter mutations are located on the surface of the DNA-binding cleft and may lead to altered template-primer positioning or conformation, causing a distortion of the geometry of the polymerase active site and consequent discrimination between normal and altered dNTP substrates. Other nucleoside analog-resistance mutations located on the periphery of the dNTP-binding site may exert their effects via altered interactions with dNTP-binding site residues. The structure of the hydrophobic region in HIV-1 RT that binds non-nucleoside inhibitors, for example, nevirapine and TIBO, has been analyzed in the absence of bound ligand. The pocket that is present when non-nucleoside inhibitors are bound is not observed in the inhibitor-free structure of HIV-1 RT with dsDNA. In particular it is filled by Tyr181 and Tyr188, suggesting that the pocket is formed primarily by rotation of these large aromatic side-chains. Existing biochemical data, taken together with the three-dimensional structure of HIV-1 RT, makes it possible to propose potential mechanisms of inhibition by non-nucleoside inhibitors. One such mechanism is local distortion of HIV-1 RT structural elements thought to participate in catalysis: the beta 9-beta 10 hairpin (which contains polymerase active site residues) and the beta 12-beta 13 hairpin (''primer grip''). An alternative possibility is restricted mobility of the p66 thumb subdomain, which is supported by the observation that structural elements of the non-nucleoside inhibitor-binding pocket may act as a ''hinge'' for the thumb. Mutations that have been shown to confer resistance to non-nucleoside inhibitors are observed to cluster around the pocket, suggesting that most of these resistance mutations lead to direct alteration of inhibitor binding. A comparison of residues in the non-nucleoside inhibitor-binding pocket of HIV-1 RT and the corresponding residues in HIV-2 RT can explain the low activity of non-nucleoside compounds against HIV-2 RT. C1 RUTGERS STATE UNIV,DEPT CHEM,PISCATAWAY,NJ 08854. RUTGERS STATE UNIV,CTR ADV BIOTECHNOL & MED,PISCATAWAY,NJ 08854. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. CATHOLIC UNIV LEUVEN,REGA INST MED RES,B-3000 LOUVAIN,BELGIUM. JANSSEN RES FDN,B-2340 BEERSE,BELGIUM. FU NCI NIH HHS [N01 CO-74101]; NIAID NIH HHS [AI 27690] NR 92 TC 438 Z9 449 U1 1 U2 23 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 OCT 28 PY 1994 VL 243 IS 3 BP 369 EP 387 DI 10.1006/jmbi.1994.1665 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PN802 UT WOS:A1994PN80200001 PM 7525966 ER PT J AU BOYER, PL FERRIS, AL CLARK, P WHITMER, J FRANK, P TANTILLO, C ARNOLD, E HUGHES, SH AF BOYER, PL FERRIS, AL CLARK, P WHITMER, J FRANK, P TANTILLO, C ARNOLD, E HUGHES, SH TI MUTATIONAL ANALYSIS OF THE FINGERS AND PALM SUBDOMAINS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) REVERSE-TRANSCRIPTASE SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE REVERSE TRANSCRIPTASE; HIV-1; MUTAGENESIS ID ESCHERICHIA-COLI; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; RNASE-H; DNA; MUTAGENESIS; IDENTIFICATION; DIMERIZATION; EXPRESSION; INHIBITOR AB We have analyzed the human immunodeficiency virus type-1 reverse transcriptase (HIV-1 RT) polymerase domain between amino acids 91 and 157 by site-directed mutagenesis. We have constructed a series of amino acid substitutions using BspMI cassettes, and have assayed the RNA-dependent DNA polymerase, DNA-dependent DNA polymerase, and RNase H activities of the mutant HIV-1 RTs. The regions of HIV-1 RT between amino acids 91 and 119 and between amino acids 151 and 157 lie within the palm subdomain and include part of the polymerase active site. A number of amino acids within these regions have been identified as being directly or indirectly involved with polymerization, since amino acid substitutions at these residues decrease the polymerase activity without affecting RNase H activity. The region of HIV-1 RT between amino acids 120 and 150 lies within the fingers subdomain of the HIV-1 polymerase. We believe that the fingers subdomain plays a role in positioning the template. Many amino acid substitutions in this region decrease or abolish both the polymerase and the RNase H functions. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21702. RUTGERS STATE UNIV,CTR ADV BIOTECHNOL & MED,PISCATAWAY,NJ 08854. FU NCI NIH HHS [N01-CO-74101] NR 33 TC 79 Z9 80 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD OCT 28 PY 1994 VL 243 IS 3 BP 472 EP 483 DI 10.1006/jmbi.1994.1673 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PN802 UT WOS:A1994PN80200009 PM 7525967 ER PT J AU CLAVERIE, JM MAKALOWSKI, W AF CLAVERIE, JM MAKALOWSKI, W TI ALU ALERT SO NATURE LA English DT Letter RP CLAVERIE, JM (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894, USA. RI Makalowski, Wojciech/I-2843-2016 NR 8 TC 35 Z9 37 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 OCT 27 PY 1994 VL 371 IS 6500 BP 752 EP 752 DI 10.1038/371752a0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PP018 UT WOS:A1994PP01800039 PM 7935834 ER PT J AU LAI, J MA, SW ZHU, RH ROTHMAN, RB LENTES, KU PORRECA, F AF LAI, J MA, SW ZHU, RH ROTHMAN, RB LENTES, KU PORRECA, F TI PHARMACOLOGICAL CHARACTERIZATION OF THE CLONED KAPPA-OPIOID RECEPTOR AS A KAPPA(1B) SUBTYPE SO NEUROREPORT LA English DT Article DE RECEPTORS; OPIOID; KAPPA SUBTYPES; CLONED KAPPA RECEPTOR; MOUSE BRAIN; RADIOLIGAND BINDING ID GUINEA-PIG BRAIN; BINDING-SITES; NALOXONE BENZOYLHYDRAZONE; DIFFERENTIAL ANTAGONISM; OPIATE RECEPTOR; MULTIPLICITY; DRUGS; ANTINOCICEPTION; FEDOTOZINE; PEPTIDES AB SUBSTANTIAL pharmacological evidence in vitro and in vivo has suggested the existence of subtypes of the kappa opioid receptor. Quantitative radioligand binding techniques resolved the presence of two high affinity binding sites for the kappa(1) ligand [H-3]U69,593 in mouse brain membranes, termed kappa(1a) and kappa(1b), respectively. Whereas the kappa(1a) site has high affinity for fedotozine and oxymorphindole and low affinity for bremazocine and alpha-neoendorphin, site kappa(1b) has high affinity for bremazocine and alpha-neoendorphin and low affinity for fedotozine and oxymorphindole. CI-977 and U69,593 bind equally well at both sites. To determine the relationship between these kappa(1) receptor subtypes and the recently cloned mouse kappa(1) receptor (KOR), we examined [H-3]U69,593 binding to the KOR in stably transfected cells (KORCHN-8). Competition of [H-3]U69,593 binding to the KOR by bremazocine, alpha-neoendorphin, fedotozine and oxymorphindole resolved a single class of binding sites at which these agents had binding affinities similar to that of the kappa(1b) site present in mouse brain. These results suggest that the cloned KOR corresponds to the kappa(1) site in mouse brain defined as kappa(1b). C1 UNIV ARIZONA,ARIZONA HLTH SCI CTR,DEPT PHARMACOL,TUCSON,AZ 85724. NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. MAX PLANCK INST BIOPHYS CHEM,GOTTINGEN,GERMANY. NR 21 TC 24 Z9 24 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD OCT 27 PY 1994 VL 5 IS 16 BP 2161 EP 2164 DI 10.1097/00001756-199410270-00043 PG 4 WC Neurosciences SC Neurosciences & Neurology GA PP741 UT WOS:A1994PP74100043 PM 7865767 ER PT J AU LEVETOWN, M POLLACK, MM CUERDON, TT RUTTIMANN, UE GLOVER, JJ AF LEVETOWN, M POLLACK, MM CUERDON, TT RUTTIMANN, UE GLOVER, JJ TI LIMITATIONS AND WITHDRAWALS OF MEDICAL INTERVENTION IN PEDIATRIC CRITICAL CARE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID NOT-RESUSCITATE ORDERS; INTENSIVE-CARE; ILL PATIENTS; ETHICS AB Objective.-To investigate the use and implementation in pediatric intensive care units (PICUs) of three levels of restriction of medical intervention: do not resuscitate (DNR), additional limitations of medical interventions beyond DNR, and withdrawal of care. Design.-Consecutive patients admitted between December 1989 and January 1992. Setting.-A total of 16 PICUs randomly selected to represent variability in size, teaching status, and presence or absence of a pediatric intensivist and unit coordination. Main Outcome Measures.-Profiles of children undergoing restrictions of medical interventions including the influence of chronic disease, the justifications for restrictions, and description of implementation practices. Patients.-All pediatric admissions undergoing restrictions (n = 119) drawn from 5415 consecutive PICU admissions. Results.-A total of 94 (79%) of the restriction patients died during the PICU course, representing 38% of all deaths. A total of 73 restrictions (61%) resulted from acute disease, most involving the central nervous system or respiratory system. Restrictions were evenly divided between DNR (39%), additional limitations of medical intervention beyond DNR (27%), and withdrawals of medical intervention (34%). Survival decreased with increasing levels of restriction from 35% of DNR patients to 9% of patients with additional limitations and 2% of withdrawal patients. Imminent death was cited as the justification for restrictions in 70% of cases, no relational potential was cited in 22%, and excessive burden was cited in 8%. Conclusions.-Restrictions of medical intervention were used in all PICUs surveyed. Although severe chronic disease was common among restriction patients, acute disease was the predominant event precipitating placement of restrictions. Imminent death, not quality of life or excessive burden, was the most common justification. C1 CHILDRENS NATL MED CTR,DEPT CRIT CARE MED,WASHINGTON,DC 20010. CHILDRENS NATL MED CTR,CTR HLTH SERV & CLIN RES,CHILDRENS RES INST,WASHINGTON,DC. CHILDRENS NATL MED CTR,DEPT PEDIAT,WASHINGTON,DC. GEORGE WASHINGTON UNIV,SCH MED,DEPT PEDIAT,WASHINGTON,DC 20052. GEORGE WASHINGTON UNIV,SCH MED,DEPT ANESTHESIOL,WASHINGTON,DC. GEORGE WASHINGTON UNIV,SCH MED,DEPT HLTH CARE SCI,WASHINGTON,DC. NIAAA,BETHESDA,MD. FU PHS HHS [MCH-110584] NR 28 TC 43 Z9 47 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 OCT 26 PY 1994 VL 272 IS 16 BP 1271 EP 1275 DI 10.1001/jama.272.16.1271 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA PN068 UT WOS:A1994PN06800033 PM 7933372 ER PT J AU ZENG, J GORSKI, RA HAMER, D AF ZENG, J GORSKI, RA HAMER, D TI DIFFERENTIAL CDNA CLONING BY ENZYMATIC DEGRADING SUBTRACTION (EDS) SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HYBRIDIZATION; PCR; FIBROBLASTS; EXPRESSION; EXTRACTION; GENES AB We describe a new method, called enzymatic degrading subtraction (EDS), for the construction of subtractive libraries from PCR amplified cDNA. The novel features of this method are that i) the tester DNA is blocked by thionucleotide incorporation; ii) the rate of hybridization is accelerated by phenol-emulsion reassociation; and iii) the driver cDNA and hybrid molecules are enzymatically removed by digestion with exonucleases III and VII rather than by physical partitioning. We demonstrate the utility of EDS by constructing a subtractive library enriched for cDNAs expressed in adult but not in embryonic rat brains. C1 UNIV CALIF LOS ANGELES,CTR HLTH SCI,SCH MED,DEPT ANAT & CELL BIOL,LOS ANGELES,CA 90024. RP ZENG, J (reprint author), NCI,BIOCHEM LAB,BLDG 37,ROOM 4A13,BETHESDA,MD 20892, USA. NR 20 TC 38 Z9 42 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 OCT 25 PY 1994 VL 22 IS 21 BP 4381 EP 4385 DI 10.1093/nar/22.21.4381 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PR180 UT WOS:A1994PR18000004 PM 7971268 ER PT J AU MAZUMDER, A GUPTA, M POMMIER, Y AF MAZUMDER, A GUPTA, M POMMIER, Y TI METHYLPHOSPHONODIESTER SUBSTITUTION NEAR THE CONSERVED CA DINUCLEOTIDE IN THE HIV LTR ALTERS BOTH EXTENT OF 3'-PROCESSING AND CHOICE OF NUCLEOPHILE BY HIV-1 INTEGRASE SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; RETROVIRAL DNA INTEGRATION; SITE-SPECIFIC HYDROLYSIS; VIRAL-DNA; PROTEIN INVITRO; POL GENE; SEQUENCE; CLEAVAGE; TERMINI AB We present evidence suggesting that the 3'-processing activity of HIV-1 integrase is dramatically affected by electrostatic and/or steric perturbations 3' to the conserved CA dinucleotide. When the phosphodiester bond 3' to the scissile phosphodiester is replaced by a methylphosphonodiester linkage, 3'-processing decreases by two orders of magnitude. This block of cleavage can be somewhat overcome by increasing the pH of the reaction. Labeling of the substrates at the 3'-end revealed blockage of water and glycerol, but stimulation of the viral DNA 3'-hydroxyl, acting as the nucleophile with the methylphosphonodiester substrate, Interestingly, a circular trinucleotide was formed using the phosphodiester and methylphosphonodiester substrates when the terminal nucleotide was 3'-deoxyadenosine but not 2'-deoxyadenosine. Mutagenesis of the enzyme active site has previously been shown to alter the choice of nucleophile in the 3'-processing reaction. Taken together, the results in this study suggest that 'mutagenesis' of the DNA backbone can also alter the choice of nucleophile. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NR 42 TC 17 Z9 17 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT 25 PY 1994 VL 22 IS 21 BP 4441 EP 4448 DI 10.1093/nar/22.21.4441 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PR180 UT WOS:A1994PR18000011 PM 7971274 ER PT J AU KOBAYASHI, N ROSENTHAL, ER YOSHIMURA, K CRYSTAL, RG AF KOBAYASHI, N ROSENTHAL, ER YOSHIMURA, K CRYSTAL, RG TI TRANSFER OF A CONSTITUTIVE VIRAL PROMOTER CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR CDNA TO HUMAN EPITHELIAL-CELLS CONVEYS RESISTANCE TO DOWN-REGULATION OF CAMP-REGULATED CL- SECRETION IN THE PRESENCE OF INFLAMMATORY STIMULI SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MEDIATED GENE-TRANSFER; DEPENDENT PROTEIN-KINASE; CHLORIDE CHANNELS; NEUTROPHIL ELASTASE; AIRWAY EPITHELIUM; TRANSPORT DEFECT; TRANSGENIC MICE; PHORBOL ESTERS; CFTR; EXPRESSION AB The expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene can be downregulated by inflammatory stimuli such as phorbol myristate acetate (PMA). Since the respiratory manifestations of cystic fibrosis (CF) are characterized by intense chronic airway inflammation very early in life, successful gene therapy far CF will require that expression of the transferred normal CFTR gene be resistant to down-regulation by inflammatory mediators. To evaluate the concept that a viral promoter - human CFTR cDNA unit would be resistant to this form of down-regulation, a retrovirus promoter (5' long terminal repeat of the Moloney murine leukemia virus)- human CFTR cDNA unit was transferred to T84 human colon carcinoma cell line using a retrovirus vector. Exposure of the retrovirus-modified T84 cells to PMA resulted in down-regulation of the endogenous CFTR mRNA transcripts (6.5 kb), but did not affect the level of exogenous CFTR transcripts (8.0 kb). Importantly, in parallel with the persistence of the exogenous CFTR transcripts, the modified cells still maintained cAMP-regulated Cl- secretion in the presence of PMA. These in vitro data suggest that a constitutive viral promoter- CFTR cDNA unit should be resistant to modulation by inflammatory stimuli, a likely requirement for successful gene therapy for CF. C1 NHLBI,PULM BRANCH,BETHESDA,MD 20892. CORNELL UNIV,COLL MED,DIV PULM & CRIT CARE MED,NEW YORK,NY. NR 47 TC 2 Z9 2 U1 0 U2 2 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 OCT 25 PY 1994 VL 22 IS 21 BP 4470 EP 4476 DI 10.1093/nar/22.21.4470 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PR180 UT WOS:A1994PR18000015 PM 7526342 ER PT J AU POSTNIKOV, YV LEHN, DA ROBINSON, RC FRIEDMAN, FK SHILOACH, J BUSTIN, M AF POSTNIKOV, YV LEHN, DA ROBINSON, RC FRIEDMAN, FK SHILOACH, J BUSTIN, M TI THE COOPERATIVE BINDING OF CHROMOSOMAL PROTEIN HMG-14 TO NUCLEOSOME CORES IS REDUCED BY SINGLE-POINT MUTATIONS IN THE NUCLEOSOMAL BINDING DOMAIN SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MOBILITY GROUP PROTEIN-14; DNA; CHROMATIN; LOCALIZATION; PARTICLES; SITES; HMG1; GENE AB Mutants of human chromosomal protein HMG-14 were generated by site directed mutagenesis and used to study functional domains in this protein. A replacement of serine by cysteine at position 7 did not affect the binding of the protein to nucleosome cores. The sulfhydryl group in the nucleosome-bound protein is accessible to modifying agents suggesting that position 7 in the protein is not in close contact with either the DNA or the histones in the core particles. Under cooperative binding conditions, replacements of alanine by proline at position 21, or of lysine by cysteine at position 26, decreased the affinity of the protein for nucleosome cores 6.7- and 3-fold respectively. In contrast, the non-cooperative mode of binding was only minimally affected. A replacement of glutamic acid by glutamine at position 76 caused only minor changes in the binding of the protein to the cores. The results indicate that single point mutations, which change either the conformation or charge in the nucleosomal binding domain of the protein, significantly reduce the ability of the HMG-14 protein to bind to nucleosome cores. We suggest that in chromatin the protein binds to nucleosomes in a cooperative manner and that upon binding to nucleosomes the protein acquires a distinct conformation. C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NIDDK,BETHESDA,MD 20892. RI Friedman, Fred/D-4208-2016; Bustin, Michael/G-6155-2015 NR 25 TC 22 Z9 22 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT 25 PY 1994 VL 22 IS 21 BP 4520 EP 4526 DI 10.1093/nar/22.21.4520 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PR180 UT WOS:A1994PR18000022 PM 7971283 ER PT J AU MAENO, M ONG, RC SUZUKI, A UENO, N KUNG, HF AF MAENO, M ONG, RC SUZUKI, A UENO, N KUNG, HF TI A TRUNCATED BONE MORPHOGENETIC PROTEIN-4 RECEPTOR ALTERS THE FATE OF VENTRAL MESODERM TO DORSAL MESODERM - ROLES OF ANIMAL POLE TISSUE IN THE DEVELOPMENT OF VENTRAL MESODERM SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EARLY AMPHIBIAN EMBRYOS; XENOPUS EMBRYOS; SPEMANN ORGANIZER; CELL LINEAGE; INDUCTION; LAEVIS; DIFFERENTIATION; IDENTIFICATION; EXPRESSION; PATTERN AB The biological effects of endogenous bone morphogenetic protein 4 (BMP-4), a member of the transforming growth factor beta family, on embryonic development of Xenopus laevis were investigated by using a functionally defective mutant of the BMP-4 receptor (Delta mTFR11), which blocks the BMP signaling pathway. Injection of Delta mTFR11 RNA into either the animal pale area or ventral marginal cells at the two-cell stage induced a dorsal phenotype in the explant of ventral mesoderm with animal pole tissue from stage 10+ embryo, even though the normal fate of this explant is a ''mesenchymal ball'' containing blood cells. These explants with the dorsal phenotype contained muscle, neural tissue, eye capsule, and cement gland. Northern blot analysis showed an increase of cardiac alpha-actin mRNA and a decrease of T alpha-globin mRNA expression, providing further evidence of a conversion from ventral to dorsal phenotype. Although injection of Delta mTFR11 RNA did not induce mesoderm in an animal cap culture, the same tissue injected with Delta mTFR11 RNA can alter the differentiation fate of uninjected ventral mesodermal explant from ventral to dorsal type, suggesting specific interaction of animal pole tissue and prospective ventral mesoderm in vivo. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,BIOCHEM PHYSIOL LAB,FREDERICK,MD 21702. HOKKAIDO UNIV,FAC PHARMACEUT SCI,SAPPORO,HOKKAIDO 060,JAPAN. NR 31 TC 141 Z9 143 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 25 PY 1994 VL 91 IS 22 BP 10260 EP 10264 DI 10.1073/pnas.91.22.10260 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PP698 UT WOS:A1994PP69800005 PM 7937937 ER PT J AU LIU, Y FIELDS, RD FESTOFF, BW NELSON, PG AF LIU, Y FIELDS, RD FESTOFF, BW NELSON, PG TI PROTEOLYTIC ACTION OF THROMBIN IS REQUIRED FOR ELECTRICAL ACTIVITY-DEPENDENT SYNAPSE REDUCTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HIRUDIN; PROTEASE NEXIN I; NEUROMUSCULAR JUNCTION; IN VITRO ID RAT SOLEUS MUSCLE; NEURO-BLASTOMA CELLS; PROTEASE NEXIN-I; NEUROMUSCULAR-JUNCTION; ELIMINATION; INHIBITORS; INNERVATION; ACTIVATION; OUTGROWTH; EXTENSION AB Molecular mechanisms of activity-dependent synapse reduction were studied in an in vitro mammalian neuromuscular preparation. Synapse reduction in this model is activity-dependent and is substantially reduced by the broad-spectrum protease inhibitor, leupeptin, suggesting the role of activity dependent proteolytic action in the process. Our present experiments show that a potent and specific thrombin inhibitor, hirudin, at nanomolar concentration completely blocked the activity-dependent synapse reduction. Furthermore, a naturally occurring serine protease inhibitor, protease nexin I (PNI), which closely colocalizes with acetylcholine receptors at the neuromuscular junction, inhibited the synapse reduction at the same low concentration. In contrast, neither cystatin, a cysteine protease inhibitor, nor aprotinin, a serine protease inhibitor that does not inhibit thrombin, blocked the synapse reduction. Similarly, neither of the inhibitors of the calcium-activated proteases calpain I and II prevented the reduction of synapses. These results strongly suggest that serine proteolytic action by thrombin or thrombin-like molecules is required for synapse reduction in our in vitro model of the mammalian neuromuscular junction. C1 NICHHD, DEV NEUROBIOL LAB, BETHESDA, MD 20892 USA. VET AFFAIRS MED CTR, NEUROBIOL RES LAB, KANSAS CITY, MO 64128 USA. UNIV KANSAS, MED CTR, DEPT NEUROBIOL, KANSAS CITY, KS 66160 USA. NR 32 TC 133 Z9 134 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 OCT 25 PY 1994 VL 91 IS 22 BP 10300 EP 10304 DI 10.1073/pnas.91.22.10300 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PP698 UT WOS:A1994PP69800013 PM 7524091 ER PT J AU COLOMBO, MF RAU, DC PARSEGIAN, VA AF COLOMBO, MF RAU, DC PARSEGIAN, VA TI REEVALUATION OF CHLORIDES REGULATION OF HEMOGLOBIN OXYGEN-UPTAKE - THE NEGLECTED CONTRIBUTION OF PROTEIN HYDRATION IN ALLOSTERISM SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BINDING; WATER; DEOXYHEMOGLOBIN; LINKAGE AB We have measured hemoglobin oxygen uptake vs. the partial pressure of oxygen, with independently controlled activities of chloride and water. This control is effected by combining different concentrations of NaCl and sucrose in the bathing solution to achieve: (i) water activities were varied and CI- activity was fixed, (ii) both water and CI- activities were varied with a traditional NaCI titration, or (iii) CI- activities were varied and water activity was fixed by adding compensating sucrose. Within this analysis, the CI--regulated loading of four oxygens can be described by the reaction Hb.CI- + 4 O-2 + 65 H2O reversible arrow Hb.4O(2).65H(2)O + CI-. The dissociation of a neatly integral chloride, rather than the nonintegral 1.6 chlorides inferred earlier from simple salt titration, demonstrates the need to recognize the potentially large contribution from changes in water activity when titrating weakly binding solutes. The single-chloride result might simplify structural considerations of the action of CI- in hemoglobin regulation. C1 NIH,DIV COMP RES & TECHNOL,STRUCT BIOL LAB,BETHESDA,MD 20892. UNIV ESTADUAL PAULISTA JULIO MESQUITA FILHO,INST BIOCIENCIAS LETRAS & CIENCIAS EXACTAS,DEPT FIS,BR-15054000 S JOSE RIO PR,SP,BRAZIL. RP COLOMBO, MF (reprint author), NIDDKD,DIV INTRAMURAL RES,BETHESDA,MD 20892, USA. RI Colombo, Marcio/K-5229-2013 OI Colombo, Marcio/0000-0003-3035-3926 NR 14 TC 35 Z9 35 U1 2 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 25 PY 1994 VL 91 IS 22 BP 10517 EP 10520 DI 10.1073/pnas.91.22.10517 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PP698 UT WOS:A1994PP69800058 PM 7937985 ER PT J AU MANN, SKO RICHARDSON, DL LEE, S KIMMEL, AR FIRTEL, RA AF MANN, SKO RICHARDSON, DL LEE, S KIMMEL, AR FIRTEL, RA TI EXPRESSION OF CAMP-DEPENDENT PROTEIN-KINASE IN PRESPORE CELLS IS SUFFICIENT TO INDUCE SPORE CELL-DIFFERENTIATION IN DICTYOSTELIUM SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SIGNAL TRANSDUCTION PATHWAYS; CYCLIC-AMP; MULTICELLULAR DEVELOPMENT; EXTRACELLULAR CAMP; GENE-EXPRESSION; DISCOIDEUM; SUBUNIT; CULMINATION; ROLES AB The activity of cAMP-dependent protein ki nase (PKA) is required for proper development at several stages during the Dictyostelium life cycle. We present evidence that activation of PKA is rate-limiting for the differentiation of prespore cells to spores and that PKA activation may be the developmental trigger for sporulation. Strains that overexpress the gene encoding the catalytic subunit of PKA (PKAcat) of lack a functional regulatory subunit (rdeC strains) undergo rapid, heterochronic development. We show that overexpression of PKAcat in prespore cells is sufficient to directly induce expression of the spore maturation marker spiA and differentiation to spores, in a cell-autonomous manner. Moreover, overexpression of PKAcat in prespore cells can bypass a mutation that blocks an earlier developmental step to induce spiA expression. Our results suggest that the regulatory pathway in prespore cells between the activation of PKA and spiA induction/spore maturation is quite short and that PKAcat expression in prespore cells may mediate spore differentiation at the level of transcription. This induction of sporulation requires the prior activation of the prespore cell pathway. In addition, we show that B-galactosidase activity expressed from a PKAcat promoter/lacZ reporter construct is highly enriched in the anterior prestalk A region during the tipped aggregate, slug, acid early culminant stages and that this pattern switches abruptly to a prespore pattern at the time of spore maturation, supporting the proposed role of PKA in this process. C1 UNIV CALIF SAN DIEGO, CTR MOLEC GENET, DEPT BIOL, LA JOLLA, CA 92093 USA. NIDDKD, CELLULAR & DEV BIOL LAB, BETHESDA, MD 20892 USA. NR 35 TC 59 Z9 61 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 OCT 25 PY 1994 VL 91 IS 22 BP 10561 EP 10565 DI 10.1073/pnas.91.22.10561 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PP698 UT WOS:A1994PP69800067 PM 7937993 ER PT J AU LETO, TL ADAMS, AG DEMENDEZ, I AF LETO, TL ADAMS, AG DEMENDEZ, I TI ASSEMBLY OF THE PHAGOCYTE NADPH OXIDASE - BINDING OF SRC HOMOLOGY-3 DOMAINS TO PROLINE-RICH TARGETS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CHRONIC GRANULOMATOUS DISEASE; CYTOCHROME B(558); P47-PHOX; P67-PHOX ID CHRONIC GRANULOMATOUS-DISEASE; RESPIRATORY BURST OXIDASE; SH3 DOMAINS; CYTOPLASMIC DOMAIN; CYTOCHROME-B; NEUTROPHIL; PROTEIN; ACTIVATION; CLONING; TRANSLOCATION AB NADPH oxidase responsible for generation of superoxide anion and related microbicidal oxidants by phagocytes is assembled from at least five distinct proteins. Two are cytosolic components (p47-phox and p67-phox) that contain Src homology 3 (SH3) domains and associate with a transmembrane cytochrome b(558) upon activation. We show here that the SH3 domains of p47-phox bind to proline-rich sequences in p47-phox itself and the p22-phox subunit of cytochrome b(558). Binding of the p47-phox SH3 domains to p22-phox was abolished by a mutation in one proline-rich sequence (pro(156) --> Gln) noted in a distinct form of chronic granulomatous disease and was inhibited by a short proline-rich synthetic peptide corresponding to residues 149-162 of p22-phox. Expression of mutated p22-phox did not restore oxidase activity to p22-phox-deficient B cells and did not enable p22-phox-dependent translocation of p47-phox to membranes in phorbol ester-stimulated cells. We also show that the cytosolic oxidase components associate with one another through the C-terminal SH3 domain of p67-phox and a proline-rich C-terminal sequence in p47-phox. These SH3 target sites conform to consensus features deduced from SH3 binding sites in other systems. We propose a model in which the oxidase complex assembles through a mechanism involving SH3 domains of both cytosolic proteins and cognate proline-rich targets in other oxidase components. RP LETO, TL (reprint author), NIAID,HOST DEF LAB,9000 ROCKVILLE PIKE,BLDG 10,ROOM 11N106,BETHESDA,MD 20892, USA. NR 32 TC 222 Z9 224 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 25 PY 1994 VL 91 IS 22 BP 10650 EP 10654 DI 10.1073/pnas.91.22.10650 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PP698 UT WOS:A1994PP69800085 PM 7938008 ER PT J AU MANDON, EC MILLA, ME KEMPNER, E HIRSCHBERG, CB AF MANDON, EC MILLA, ME KEMPNER, E HIRSCHBERG, CB TI PURIFICATION OF THE GOLGI ADENOSINE 3'-PHOSPHATE 5'-PHOSPHOSULFATE TRANSPORTER, A HOMODIMER WITHIN THE MEMBRANE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SULFATION; PROTEOGLYCANS; GLYCOPROTEINS; GLYCOLIPIDS ID RAT-LIVER GOLGI; SACCHAROMYCES-CEREVISIAE; GUANOSINE DIPHOSPHATASE; NUCLEOTIDE SULFATE; VESICLES; SIALYLTRANSFERASE; SULFOTRANSFERASE; RECONSTITUTION; TRANSLOCATION; GLYCOSYLATION AB Sulfation of proteoglycans, secretory and membrane proteins, and glycolipids occurs in the lumen of the Golgi apparatus. Adenosine 3'-phosphate 5'-phosphosulfate (PAPS), the sulfate donor in these reactions, must be transported from the cytosol, its site of synthesis, into the lumen of the Golgi apparatus. We have identified and purified to apparent homogeneity the rat liver Golgi membrane PAPS transporter by a combination of conventional and affinity chromatography as well as photoaffinity radiolabeling with adenosine 3',5'-bisphosphate, a competitive inhibitor of PAPS transport. The transporter, a 75-kDa protein, was purified 70,000-fold over homogenate (6% yield) and transported PAPS into phosphatidylcholine liposomes selectively and in a saturable manner (apparent K-m of 1.7 mu M). Radiation target inactivation analyses of the transport activity in rat liver Golgi vesicles, together with the above described biochemical apl preaches, demonstrate that the PAPS transporter within the Golgi membrane is a homodimer. C1 NIAMS,PHYS BIOL LAB,BETHESDA,MD 20892. RP MANDON, EC (reprint author), UNIV MASSACHUSETTS,MED CTR,DEPT BIOCHEM & MOLEC BIOL,WORCESTER,MA 01655, USA. FU NIGMS NIH HHS [GM34396] NR 30 TC 60 Z9 60 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 25 PY 1994 VL 91 IS 22 BP 10707 EP 10711 DI 10.1073/pnas.91.22.10707 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PP698 UT WOS:A1994PP69800097 PM 7938015 ER PT J AU GUZMAN, RJ HIRSCHOWITZ, EA BRODY, SL CRYSTAL, RG EPSTEIN, SE FINKEL, T AF GUZMAN, RJ HIRSCHOWITZ, EA BRODY, SL CRYSTAL, RG EPSTEIN, SE FINKEL, T TI IN-VIVO SUPPRESSION OF INJURY-INDUCED VASCULAR SMOOTH-MUSCLE CELL ACCUMULATION USING ADENOVIRUS-MEDIATED TRANSFER OF THE HERPES-SIMPLEX VIRUS THYMIDINE KINASE GENE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GENE THERAPY; RESTENOSIS ID RECOMBINANT ADENOVIRUS; CORONARY ANGIOPLASTY; RETROVIRAL VECTOR; BRAIN-TUMORS; IN-VIVO; INVIVO; PROLIFERATION; EXPRESSION; INHIBITION; ARTERIES AB Restenosis, a process characterized in part by excessive smooth muscle cell (SMC) proliferation in areas of vascular injury, occurs in up to 50% of patients undergoing balloon angioplasty. In an effort to develop a treatment strategy for restenosis, we constructed a replication-deficient recombinant adenovirus (AdMLP.HSTK) containing the herpes simplex virus thymidine kinase gene (HSV tk). This viral gene product phosphorylates the prodrug ganciclovir tb form a nucleoside analog that inhibits DNA synthesis. Cultured primary rat SMCs infected with AdMLP.HSTK were completely growth-inhibited by incubation in ganciclovir-containing medium. In addition, when only a portion of the SMC population received the HSV tk transgene, an inhibitory effect on neighboring SMCs was evident. evaluation of this strategy in vivo using a rat carotid balloon injury model demonstrated that local infection of injured arteries with AdMLP.HSTK followed by 2 weeks of systemic ganciclovir treatment significantly (P < 0.01) reduced injury-induced SMC accumulation. In contrast, there was no suppression of injury-induced SMC accumulation in animals infected with AdMLP.HSTK but not receiving ganciclovir or in those animals infected with a control adenovirus and either treated or not treated with ganciclovir. These results demonstrate the potential utility of adenovirus-mediated gene transfer for treatment of restenosis after balloon injury. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. CORNELL UNIV,MED CTR,NEW YORK HOSP,DIV PULM & CRIT CARE MED,NEW YORK,NY 10021. NR 37 TC 172 Z9 173 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 25 PY 1994 VL 91 IS 22 BP 10732 EP 10736 DI 10.1073/pnas.91.22.10732 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PP698 UT WOS:A1994PP69800102 PM 7938020 ER PT J AU NEEL, JV BIGGAR, RJ SUKERNIK, RI AF NEEL, JV BIGGAR, RJ SUKERNIK, RI TI VIROLOGICAL AND GENETIC-STUDIES RELATE AMERIND ORIGINS TO THE INDIGENOUS PEOPLE OF THE MONGOLIA MANCHURIA SOUTHEASTERN SIBERIA REGION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HUMAN T-CELL LYMPHOTROPHIC VIRUS TYPE II IN SIBERIA; AMERINDIAN ORIGINS; MTDNA IN SIBERIA ID HTLV-II INFECTION; CELL LYMPHOTROPIC VIRUS; MITOCHONDRIAL-DNA POLYMORPHISM; MONGOLIAN POPULATION; ENDEMIC POPULATION; ASIAN POPULATIONS; NATIVE-AMERICANS; GUAYMI INDIANS; LEUKEMIA; MTDNA AB A commonly held theory is that the first wave of migrants into the New World was derivative from the ethnic groups then inhabiting eastern Siberia. However, these ethnic groups jack a mtDNA haplogroup (B) that is well represented in Amerindian tribes. Also, the time depth of the other three mtDNA haplogroups found in Amerindians (A, C, and D) appears to be greater in the Amerindians than in the eastern Siberian ethnic groups. In this communication we demonstrate that the human T-cell lymphotrophic virus type II, present in 11 of the 38 Amerindian tribes thus far examined, is not present in any of the 10 ethnic groups of eastern Siberia that we have studied. However, the virus has just been reported in the indigenous population of Mongolia, and mtDNA haplogroup B is also represented in this region. On the basis of these facts, we propose that the ancestors of the first migrants to the New World were not derived from north and central Siberia but from populations to the south, inhabiting the regions of Mongolia, Manchuria, and/or the extreme southeastern tip of Siberia. C1 NCI,DIV CANC ETIOL,VIRAL EPIDEMIOL SECT,ROCKVILLE,MD 20852. RUSSIAN ACAD SCI,INST CYTOL & GENET,NOVOSIBIRSK 630090,RUSSIA. RP NEEL, JV (reprint author), UNIV MICHIGAN,SCH MED,DEPT HUMAN GENET,ANN ARBOR,MI 48109, USA. RI Sukernik, Rem/N-6990-2015 NR 50 TC 86 Z9 86 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 25 PY 1994 VL 91 IS 22 BP 10737 EP 10741 DI 10.1073/pnas.91.22.10737 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PP698 UT WOS:A1994PP69800103 PM 7938021 ER PT J AU FERRARIS, JD WILLIAMS, CK MARTIN, BM BURG, MB GARCIAPEREZ, A AF FERRARIS, JD WILLIAMS, CK MARTIN, BM BURG, MB GARCIAPEREZ, A TI CLONING, GENOMIC ORGANIZATION, AND OSMOTIC RESPONSE OF THE ALDOSE REDUCTASE GENE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE OSMOREGULATION; OSMOTIC STRESS; ORGANIC OSMOLYTES; GENE REGULATION; GENE EXPRESSION ID RENAL MEDULLARY CELLS; EXTRACELLULAR NACL; PROTEIN; INDUCTION; PROMOTER; STRESS; DNA; RAT AB Diverse organisms accumulate organic osmolytes to adapt to hyperosmotic stress. The molecular basis of eukaryotic gene osmoregulation remains obscure. Aldose reductase [AR; alditol:NAD(P)(+) 1-oxidoreductase, EC 1.1.1.21], which catalyzes the conversion of glucose to sorbitol (an organic osmolyte), is induced in renal medullary tells under hyperosmotic conditions. Elevated extracellular NaCl increases AR mRNA transcription in PAP-HT25 cells, a cell line derived from the rabbit renal papilla. We have cloned and characterized the rabbit AR gene to determine how it is regulated by hyperosmolality. The length of the gene, not including 5' or 3' flanking regions, is approximately 14.7 kilobases (kb) organized into 10 exons and 9 introns. The transcription start site is 36 base pairs upstream of the initiator methionine codon. A 5-kb fragment containing approximately 3.5 kb of 5' flanking region was isolated. The 3.5-kb sequence was examined for basal promoter activity and hyperosmotic response in luciferase reporter gene constructs. A 235-base-pair fragment (base pairs -208 to +27) was able to drive the downstream reporter gene in transfected PAP-HT25 cells under isoosmotic conditions (300 mosmol/kg of H2O). When this fragment plus the remaining upstream sequence (from approximately base pair -3429 to base pair +27) was used, cells in hyperosmotic medium (500 mosmol/kg of H2O) showed about 40-fold induction of luciferase expression compared with cells in isoosmotic medium. The upstream fragment (from approximately base pair -3429 to base pair -192) also conferred osmotic response to a heterologous promoter (B19). This finding evidences putative osmotic response element(s) (OREs) within a specific DNA fragment in a eukaryotic genome. Identification and characterization of OREs within this fragment and their associated trans-acting factors should reveal the molecular mechanisms of gene regulation in osmotic stress. C1 NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. NR 24 TC 68 Z9 69 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 25 PY 1994 VL 91 IS 22 BP 10742 EP 10746 DI 10.1073/pnas.91.22.10742 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PP698 UT WOS:A1994PP69800104 PM 7938022 ER PT J AU MUTOH, T TOKUDA, A MARINI, AM FUJIKI, N AF MUTOH, T TOKUDA, A MARINI, AM FUJIKI, N TI 1-METHYL-4-PHENYLPYRIDINUM KILLS DIFFERENTIATED PC12 CELLS WITH A CONCOMITANT CHANGE IN PROTEIN-PHOSPHORYLATION SO BRAIN RESEARCH LA English DT Article DE 1-METHYL-4-PHENYLPYRIDINUM; PC12 CELL; NERVE GROWTH FACTOR; S6 PROTEIN; APOPTOSIS ID NERVE GROWTH-FACTOR; RIBOSOMAL PROTEIN-S6; FACTOR DEPRIVATION; SUBSTANTIA NIGRA; DEATH; ION; PC12-CELLS; APOPTOSIS; TOXICITY; NEURONS AB 1-Methyl-4-phenylpyridinum (MPP(+)), a selective neurotoxin, destroys the dopaminergic nigrostriatal pathway and results in a parkinsonian syndrome. Exposure of differentiated PC12 cells with nerve growth factor for 5 days to MPP(+) (100 mu M) for 4 h induced DNA fragmentation which is typical for the programmed cell death. MPP(+) treatment (100 mu M) concomitantly stimulates S6 kinase activity and resultant phosphorylation of S6 protein of 40S ribosomal subunits in the cells. Cycloheximide treatment prevents the MPP(+)-induced DNA fragmentation and enhancement of the phosphorylation of S6 protein. The present data demonstrate that neurotoxin, MPP(+), kills differentiated PC12 cells by the apparent involvement of apoptotic process. Furthermore, the data strongly suggest that a change in protein phosphorylation might be involved in the signal transduction of MPP(+) neurotoxicity and/or the protection from its toxicity. C1 NIMH,CLIN NEUROSCI BRANCH,MOLEC PHARMACOL SECT,BETHESDA,MD 20892. RP MUTOH, T (reprint author), FUKUI MED SCH,DEPT INTERNAL MED 2,DIV NEUROL,23 SHIMOAIZUKI,MATSUOKA,FUKUI 91011,JAPAN. NR 20 TC 33 Z9 33 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 OCT 24 PY 1994 VL 661 IS 1-2 BP 51 EP 55 DI 10.1016/0006-8993(94)91179-7 PG 5 WC Neurosciences SC Neurosciences & Neurology GA PM463 UT WOS:A1994PM46300007 PM 7834384 ER PT J AU DRUGAN, RC BASILE, AS HA, JH FERLAND, RJ AF DRUGAN, RC BASILE, AS HA, JH FERLAND, RJ TI THE PROTECTIVE EFFECTS OF STRESS-CONTROL MAY BE MEDIATED BY INCREASED BRAIN LEVELS OF BENZODIAZEPINE RECEPTOR AGONISTS SO BRAIN RESEARCH LA English DT Review DE STRESS CONTROL; COPING; PICROTOXININ; STRYCHNINE; SEIZURE; CHLORIDE CHANNEL; TBPS; RECEPTOR BINDING; GABA SHIFT; ANTICONVULSANT; ENDOGENOUS BENZODIAZEPINE ID SINGLE UNIT-ACTIVITY; KILLER-CELL ACTIVITY; RAT CEREBRAL-CORTEX; INESCAPABLE SHOCK; LOCUS COERULEUS; LEARNED HELPLESSNESS; HEPATIC-ENCEPHALOPATHY; BEHAVIORAL DEPRESSION; ANIMAL-MODEL; ANTICONVULSANT PROFILE AB Control over stress protects against many of the deleterious effects of stress exposure, but the endogenous mediators responsible for these prophylactic effects have remained elusive. Using behavioral pharmacology, in vitro radioligand binding and neurochemical analyses, we demonstrate that exposure to escapable stress results in brain and behavior changes reminiscent of benzodiazepine administration. The stress control group shows significant protection against picrotoxinin-induced seizures, reductions in [S-35]t-butylbicyclophosphorothionate (TBPS) binding and a 3-fold increase of benzodiazepine-like substances in brain in comparison to both yoked-inescapable shock and non-shock controls. These observations suggest that coping behavior leads to the release of endogenous benzodiazepine-like compounds in brain which protect the organism from stress pathology. C1 NIDDK,NEUROSCI LAB,BETHESDA,MD 20892. RP DRUGAN, RC (reprint author), BROWN UNIV,DEPT PSYCHOL,SCHRIER RES LAB,BOX 1853,89 WATERMAN ST,PROVIDENCE,RI 02912, USA. RI Ferland, Russell/E-3500-2010; OI Ferland, Russell/0000-0002-8044-2479 FU NIMH NIH HHS [MH 45475] NR 107 TC 37 Z9 37 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 OCT 24 PY 1994 VL 661 IS 1-2 BP 127 EP 136 DI 10.1016/0006-8993(94)91189-4 PG 10 WC Neurosciences SC Neurosciences & Neurology GA PM463 UT WOS:A1994PM46300017 PM 7834364 ER PT J AU SZALLASI, A BLUMBERG, PM NILSSON, S HOKFELT, T LUNDBERG, JM AF SZALLASI, A BLUMBERG, PM NILSSON, S HOKFELT, T LUNDBERG, JM TI VISUALIZATION BY [H-3] RESINIFERATOXIN AUTORADIOGRAPHY OF CAPSAICIN-SENSITIVE NEURONS IN THE RAT, PIG AND MAN SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Note DE [H-3] RESINIFERATOXIN; AUTORADIOGRAPHY; VANILLOID RECEPTOR; CAPSAICIN-SENSITIVE NEURON; DORSAL ROOT GANGLIA; SPINAL ID SENSORY NEURONS; ADULT-RAT; RESINIFERATOXIN; BINDING; RECEPTOR AB [H-3]Resiniferatoxin autoradiography revealed high densities of binding sites in rat dorsal root ganglia as well as in the superficial dorsal horn of the spinal cord, known to contain the cell bodies and central terminals, respectively, of capsaicin-sensitive, sensory neurons. This binding was fully displaced by non-radioactive resiniferatoxin and was absent following administration of high, neurotoxic doses of capsaicin. The binding thus has the characteristics expected for the vanilloid (capsaicin) receptor. High density, specific resiniferatoxin binding was also observed in pig spinal cord and dorsal root ganglia. Finally, similar high density binding was detected in the dorsal horn of human spinal cord obtained post-mortem. We conclude that [H-3]resiniferatoxin autoradiography may afford a novel neurochemical tool to identify capsaicin-sensitive neurons in the central as well as in the peripheral nervous system, to explore the ontogeny of these neurons, and to detect changes in vanilloid (capsaicin) receptor expression under pathophysiological conditions. C1 NCI,BETHESDA,MD 20892. KAROLINSKA INST,DEPT NEUROSCI,S-17177 STOCKHOLM,SWEDEN. RP SZALLASI, A (reprint author), KAROLINSKA INST,DEPT PHYSIOL & PHARMACOL,DIV PHARMACOL,S-17177 STOCKHOLM,SWEDEN. NR 13 TC 28 Z9 29 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD OCT 24 PY 1994 VL 264 IS 2 BP 217 EP 221 DI 10.1016/0014-2999(94)00526-5 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PN917 UT WOS:A1994PN91700015 PM 7851486 ER PT J AU SIDRANSKY, E DIETRICH, KM GINNS, EI AF SIDRANSKY, E DIETRICH, KM GINNS, EI TI FALSE-POSITIVE PREGNANCY TESTS IN GAUCHERS-DISEASE SO LANCET LA English DT Letter C1 NIH,DEPT NURSING,CTR CLIN,BETHESDA,MD 20892. RP SIDRANSKY, E (reprint author), NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD OCT 22 PY 1994 VL 344 IS 8930 BP 1156 EP 1156 DI 10.1016/S0140-6736(94)90662-9 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PN066 UT WOS:A1994PN06600042 PM 7934511 ER PT J AU WANG, JB JOHNSON, PS WU, JM WANG, WF UHL, GR AF WANG, JB JOHNSON, PS WU, JM WANG, WF UHL, GR TI HUMAN KAPPA-OPIATE RECEPTOR 2ND EXTRACELLULAR LOOP ELEVATES DYNORPHINS AFFINITY FOR HUMAN MU/KAPPA CHIMERAS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID DELTA-OPIOID RECEPTOR; FORMYL PEPTIDE RECEPTOR; LIGAND-BINDING; EXPRESSION; CLONING; DOMAINS; ANTAGONIST; AGONISTS; CDNA AB To investigate roles of second extracellular loop sequences in peptide and nonpeptide ligand recognition by human opiate receptors, we have constructed a chimeric receptor in which this domain of the human mu opiate receptor has been replaced with that of the human kappa opiate receptor. The chimeric opiate receptor displays dramatically increased affinity for dynorphin peptides. Affinities for dynorphin A-(1-17), dynorphin A-(1-13), and alpha-neoendorphin increase by up to 250-fold when compared with the wild-type human mu opiate receptor. The chimera maintains recognition of the mu-selective ligands morphine and [D-Ala(2),MePhe(4),Gly-ol(5)] enkephalin and displays no significant changes in affinity for the kappa-selective small molecule ligand U50,488. The chimeric opiate receptor displays evidence for effective G-protein coupling; 100 nM dynorphin A-(1-17) is as effective as 100 nM morphine at inhibiting forskolin-stimulated adenyl cyclase activity through actions at the chimeric receptor. These data suggest that the putative second extracellular loop contributes substantially to the kappa receptor's selectivity in dynorphin ligand recognition. C1 NIDA,MOLEC NEUROBIOL BRANCH,BALTIMORE,MD 21224. NIDA,INTRAMURAL RES PROGRAM,OFF DIRECTOR,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. NR 21 TC 111 Z9 113 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 OCT 21 PY 1994 VL 269 IS 42 BP 25966 EP 25969 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ930 UT WOS:A1994PQ93000007 PM 7929306 ER PT J AU HUANG, S FORTUNE, KP WANK, SA KOPIN, AS GARDNER, JD AF HUANG, S FORTUNE, KP WANK, SA KOPIN, AS GARDNER, JD TI MULTIPLE AFFINITY STATES OF DIFFERENT CHOLECYSTOKININ RECEPTORS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PANCREATIC ACINAR-CELLS; FUNCTIONAL EXPRESSION; GASTRIN RECEPTOR; ANTAGONIST RADIOLIGAND; MOLECULAR-CLONING; PARIETAL-CELLS; CCK; BINDING; BRAIN; L365,260 AB We transfected COS cells with cDNA for rat cholecystokinin-A (CCK-A) and different CCK-B receptors and measured binding of I-125-CCK-8, [H-3]L-364,718 and [H-3]L-365,260 to characterize the different affinity states for each type of CCH receptor. Rat CCK-A and CCK-B receptors, canine CCK-B receptors and canine mutant CCK-B (M-CCK-B) receptors in which the leucine in position 355 was replaced by valine each existed in three differ ent affinity states for CCK-8, high affinity, low affinity, and very ion: affinity. In rat CCK-A and probably CCK-B receptors, most were in the very low affinity state, whereas with canine CCK-B and M-CCK-B receptors, most were in the low affinity state. Studies with CCK receptor agonists, CCK-8, gastrin, and CCK-JMV-180, in conjunction with CCK receptor antagonists, L-364,718 and L-365,260, showed a different pattern of affinities for these ligands at the different CCK receptors. Thus, each transfected CCK receptor can exist in three different affinity states for CCK-8 and has a characteristic pattern of interaction with different ligands. This ability to exist in multiple affinity states is an intrinsic property of the CCK receptor molecule itself. C1 ST LOUIS UNIV,HLTH SCI CTR,DEPT INTERNAL MED,ST LOUIS,MO 63104. NIDDK,DIGEST DIS BRANCH,BETHESDA,MD 20892. TUFTS UNIV,NEW ENGLAND MED CTR,SCH MED,DIV GASTROENTEROL,BOSTON,MA 02111. TUFTS UNIV,NEW ENGLAND MED CTR,SCH MED,CTR GASTROENTEROL RES ABSORPY,BOSTON,MA 02111. TUFTS UNIV,NEW ENGLAND MED CTR,SCH MED,CTR SECRETORY PROC DIGEST DIS,BOSTON,MA 02111. FU NHLBI NIH HHS [HL23632]; NIEHS NIH HHS [ES00210] NR 19 TC 60 Z9 61 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 OCT 21 PY 1994 VL 269 IS 42 BP 26121 EP 26126 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ930 UT WOS:A1994PQ93000030 PM 7929324 ER PT J AU ARORA, N WILLIAMSON, LC LEPPLA, SH HALPERN, JL AF ARORA, N WILLIAMSON, LC LEPPLA, SH HALPERN, JL TI CYTOTOXIC EFFECTS OF A CHIMERIC PROTEIN CONSISTING OF TETANUS TOXIN LIGHT-CHAIN AND ANTHRAX TOXIN LETHAL FACTOR IN NONNEURONAL CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INTEGRAL MEMBRANE-PROTEIN; PROTECTIVE ANTIGEN; NEUROTRANSMITTER RELEASE; ESCHERICHIA-COLI; SPINAL-CORD; INHIBITS EXOCYTOSIS; BOTULINUM TOXINS; HEAVY-CHAIN; CYCLIC-AMP; FUSION AB The light chain of tetanus toxin is a zinc endoprotease that inhibits neurotransmitter release by selective proteolysis of the synaptic vesicle-associated protein synaptobrevin/vesicle-associated membrane protein. Cellubrevin is a homologue of synaptobrevin that is found in most cell types and is also a substrate for tetanus toxin. The lack of receptors for tetanus toxin on most cell types has made studies of tetanus toxin action in non-neuronal cells difficult. To characterize tetanus toxin effects in non-neuronal cells, a fusion protein consisting of the 254 amino-terminal amino acids of lethal factor (LF) of anthrax toxin and tetanus toxin light chain (LC) was prepared. This protein (LF-LC) inhibited evoked glycine release from primary spinal cord neurons at concentrations between 1.0 and 100 ng/ml. LF-LC was cytotoxic to RAW 264.7, ANA-1 cells (mouse macrophage cell lines), and Chinese hamster ovary cells in a dose-dependent manner. These effects required the presence of protective antigen, the receptor binding component of anthrax toxin. In contrast, LF-LC was not cytotoxic to RBL-2H3, Vero, or mouse hybridoma cell lines. Mutagenesis of conserved amino acids (His(237) and Glu(234)) in the zinc-binding motif of LC resulted in fusion proteins having no biological activity. LF LC did not inhibit regulated secretion of serotonin in RBL-2H3 cells or constitutive secretion in any non-neuronal cell lines as measured in several different assays. We suggest that the cytotoxic effects of LF-LC result from inhibition of a specific intracellular membrane fusion event mediated by cellubrevin. C1 US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,BETHESDA,MD 20892. NIDR,MICROBIAL ECOL LAB,BETHESDA,MD 20892. NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD 20892. NR 58 TC 44 Z9 44 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 OCT 21 PY 1994 VL 269 IS 42 BP 26165 EP 26171 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ930 UT WOS:A1994PQ93000036 PM 7929330 ER PT J AU WINDSOR, LJ BODDEN, MK BIRKEDALHANSEN, B ENGLER, JA BIRKEDALHANSEN, H AF WINDSOR, LJ BODDEN, MK BIRKEDALHANSEN, B ENGLER, JA BIRKEDALHANSEN, H TI MUTATIONAL ANALYSIS OF RESIDUES IN AND AROUND THE ACTIVE-SITE OF HUMAN FIBROBLAST-TYPE COLLAGENASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MATRIX METALLOPROTEINASES; CYSTEINE SWITCH; ACTIVATION; PROCOLLAGENASE; THERMOLYSIN; FAMILY; IDENTIFICATION; INHIBITORS; PRINCIPLE; PROTEINS AB Mutants in and around the catalytic zinc-binding site of human fibroblast-type collagenase have been expressed in Escherichia coli. Replacement of each of the three zinc ligands, His-199, His-203, and His-209, in the active site sequence: VAAHEXGHXXGXXH, not only destroyed catalytic activity but also led to improper folding of the polypeptide, suggesting that this sequence also serves as a structural zinc-binding site. By comparison, mutation of His-194 immediately preceding this sequence had no measurable effect on catalytic activity or on folding. Replacement of Glu-200 in the active site yielded enzymes that either were completely inactive (E200Q) or had greatly diminished (E200D) catalytic activity. Both Glu-200 mutants, however, were fully capable of forming complexes with tissue inhibitor of metalloproteinases-1 (TIMP-1) after reaction with organomercurials. Formation of complexes with TIMP-1 appear to require a properly folded, but not necessarily catalytically competent, active site. By contrast, complexes with alpha(2)-macroglobulin form only with mutants with a catalytically competent active site. Two mutants identified in this study (E200Q and D212E) appeared to be properly folded but unable to generate any catalytic activity when exposed to either p-aminophenylmercuric acetate, trypsin, or SDS. C1 UNIV ALABAMA,SCH DENT,DEPT ORAL BIOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,SCH DENT,ORAL BIOL RES CTR,BIRMINGHAM,AL 35294. UNIV ALABAMA,SCH DENT,DEPT DIAGNOST SCI,BIRMINGHAM,AL 35294. UNIV ALABAMA,SCH DENT,DEPT RESTORAT DENT,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT PATHOL,BIRMINGHAM,AL 35294. NIDR,BETHESDA,MD 20892. RP WINDSOR, LJ (reprint author), UNIV ALABAMA,DEPT MOLEC GENET & BIOCHEM,BIRMINGHAM,AL 35294, USA. FU NIDCR NIH HHS [DE08228, DE09122, DE06028] NR 33 TC 52 Z9 52 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 OCT 21 PY 1994 VL 269 IS 42 BP 26201 EP 26207 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ930 UT WOS:A1994PQ93000042 PM 7929334 ER PT J AU JOST, CR KURUCZ, I JACOBUS, CM TITUS, JA GEORGE, AJT SEGAL, DM AF JOST, CR KURUCZ, I JACOBUS, CM TITUS, JA GEORGE, AJT SEGAL, DM TI MAMMALIAN EXPRESSION AND SECRETION OF FUNCTIONAL SINGLE-CHAIN FV MOLECULES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID T-CELL RECEPTORS; ENDOPLASMIC-RETICULUM; MONOCLONAL-ANTIBODY; ESCHERICHIA-COLI; LIGHT-CHAINS; GLYCOSYLATION SITES; VARIABLE PORTIONS; DISULFIDE BOND; PROTEIN; IMMUNOGLOBULIN AB Single chain Fv (sFv) proteins are genetically engineered molecules that consist of the two variable domains of an antibody connected by a polypeptide linker; they contain the antigen binding function of the parental protein in a single 30-kDa polypeptide chain. sFvs are usually produced in bacteria where they are insoluble and therefore require extensive refolding in vitro. In this report we followed the processing of three antibody sFvs (145-2C11 directed against murine CD3 epsilon chain, OKT9 against the human transferrin receptor, and U7.6 against dinitrophenyl groups) by transfected mammalian (COS-7) cells to determine whether the mammalian protein folding machinery can produce and secrete active sFv with high efficiency. The sFvs contained an immunoglobulin light chain leader sequence, which directed them to the endoplasmic reticulum and allowed secretion into the medium. We found that the sFvs were secreted at different rates, with the rate-limiting step of secretion being their exit from the endoplasmic reticulum. We increased the secretion rate of one of the sFvs by introducing an asparagine-linked glycosylation site in FR1 of the heavy chain, and by using tunicamycin (an inhibitor of glycosylation) we found that glycosylated antibody sFvs were secreted faster than their nonglycosylated counterparts. All secreted sFvs specifically bound their antigens; where tested, at least 90% of the secreted sFv was functional. Therefore, mammalian cells can effectively fold and secrete sFv antibody and can provide a convenient system for testing and producing sFv proteins. C1 NCI, EXPTL IMMUNOL BRANCH, BETHESDA, MD 20892 USA. OI George, Andrew/0000-0002-2866-0241 NR 42 TC 52 Z9 52 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 21 PY 1994 VL 269 IS 42 BP 26267 EP 26273 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ930 UT WOS:A1994PQ93000052 PM 7929344 ER PT J AU HAFT, CR KLAUSNER, RD TAYLOR, SI AF HAFT, CR KLAUSNER, RD TAYLOR, SI TI INVOLVEMENT OF DILEUCINE MOTIFS IN THE INTERNALIZATION AND DEGRADATION OF THE INSULIN-RECEPTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LYSOSOMAL MEMBRANE GLYCOPROTEIN; MANNOSE 6-PHOSPHATE RECEPTOR; TYROSINE KINASE-ACTIVITY; FACTOR-II RECEPTOR; CYTOPLASMIC DOMAIN; JUXTAMEMBRANE REGION; TRANSFERRIN RECEPTOR; BETA-HEXOSAMINIDASE; AMINO-ACIDS; ENDOCYTOSIS AB Dileucine motifs have been shown to be involved in trans Golgi sorting, lysosomal targeting, and internalization of a number of proteins. The insulin receptor contains four dileucine pairs in its cytoplasmic domain. To determine if these insulin receptor sequences can serve as lysosomal sorting sequences, chimeric molecules expressing the Tac antigen fused to each isolated insulin receptor motif were constructed. A chimera con taining the juxtamembrane dileucine motif (EKITLL), which closely resembles the sequences originally identified in the gamma- and delta-chains of the T cell receptor (DKQTLL and EVQALL), was shown to sort to lysosomes by immunofluorescence microscopy, as did a chimera expressing the dileucine motif (GGKGLL) found in the tyrosine kinase domain. Chimeras expressing either a second tyrosine kinase domain sequence (HVVRLL) or the carboxyl-terminal sequence (EIVNLL) localized to both lysosomes and the plasma membrane. In contrast, chimeras expressing two other potential sorting signals found in the cytoplasmic tail of the insulin receptor (NARDII and KNGRIL) localized predominantly to the plasma membrane. Exclusively cell surface staining was also seen for a chimera expressing a mutant motif (EKITAA), where the leucine residues were mutated to alanines. When the alanine pair was introduced into the juxtamembrane domain of the intact insulin receptor and the mutant receptor expressed in NM-3T3 cells, we found that the mutation did not impair insulin binding or receptor tyrosine kinase activity. However, the Ala-Ala mutant internalized insulin 5-fold slower than the wild-type receptor. Taken together, these findings suggest that the dileucine motif found in the juxtamembrane domain of the insulin receptor is involved in receptor internalization and that other insulin receptor sequences may mask the potential lysosomal targeting signals in the intact molecule. C1 NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. NR 59 TC 70 Z9 70 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 OCT 21 PY 1994 VL 269 IS 42 BP 26286 EP 26294 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ930 UT WOS:A1994PQ93000055 PM 7929346 ER PT J AU AHUJA, SK SHETTY, A TIFFANY, HL MURPHY, PM AF AHUJA, SK SHETTY, A TIFFANY, HL MURPHY, PM TI COMPARISON OF THE GENOMIC ORGANIZATION AND PROMOTER FUNCTION FOR HUMAN INTERLEUKIN-8 RECEPTOR-A AND RECEPTOR-B SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMINO TERMINUS; HUMAN DNA; GENE; EXPRESSION; SEQUENCE; NEUTROPHIL; CLONING; PROTEIN; CLUSTER; CELLS AB Human neutrophils are highly responsive to the chemokine interleukin-8 (IL-8) owing to high levels of expression of two related receptors encoded by the single copy genes il8ra and il8rb located on chromosome 2q34-q35. To identify nuclear factors that regulate the expression of IL-8 receptors, we have first defined the organization of both genes and characterized their functional promoters. il8ra and il8rb span similar to 4 and 12 kilobase pairs of genomic DNA, respectively. In both cases, the open reading frame resides on a single exon. In contrast, the 5'-untranslated regions are more complex. For il8ra, it is formed from two exons, whereas for il8rb, seven distinct neutrophil mRNAs are formed by alternative splicing of 11 exons. One of the splice variants, designated IL8RB3, is the predominant form for il8rb. Two equally abundant mRNAs for il8ra, 2.0 and 2.4 kilobases in length, are expressed in neutrophils and arise from usage of two alternative polyadenylation signals. Primer extension analysis identified two major transcription start points for il8ra and 11 for il8rb. Regions extending 300 base pairs (bp) upstream from exon 1 of il8ra and 81 bp upstream from exon 3 of il8rb have limited sequence similarity but had strong constitutive promoter activity when cloned upstream from a chloramphenicol acetyltransferase-encoding reporter gene and transiently transfected into surrogate myeloid (HL-60, and U-937) and lymphoid (Jurkat) cell lines. Neither of these regions has sequences corresponding to classic promoter elements. In contrast, a region 643 base pairs upstream from exon 1 of il8rb had relatively low levels of constitutive promoter activity in all three cell environments, and a conserved TATA element is located 47 bp upstream of the 5'-end of exon 1. Thus, despite marked differences in the complexity of their genomic organization, il8ra and il8rb encode products that are similar in structure, function, and the major cell type of expression. RP AHUJA, SK (reprint author), NIAID,HOST DEF LAB,BLDG 10,RM 11N113,BETHESDA,MD 20892, USA. NR 27 TC 62 Z9 64 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 21 PY 1994 VL 269 IS 42 BP 26381 EP 26389 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ930 UT WOS:A1994PQ93000068 PM 7929358 ER PT J AU VERONESE, FDM WILLIS, AE BOYERTHOMPSON, C APPELLA, E PERHAM, RN AF VERONESE, FDM WILLIS, AE BOYERTHOMPSON, C APPELLA, E PERHAM, RN TI STRUCTURAL MIMICRY AND ENHANCED IMMUNOGENICITY OF PEPTIDE EPITOPES DISPLAYED ON FILAMENTOUS BACTERIOPHAGE - THE V3 LOOP OF HIV-1 GP120 SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE FILAMENTOUS BACTERIOPHAGE; PEPTIDE EPITOPES; STRUCTURAL MIMICRY; HIV GP120; VACCINE DESIGN ID IMMUNODEFICIENCY-VIRUS TYPE-1; PRINCIPAL NEUTRALIZING DETERMINANT; ENVELOPE PROTEIN; MULTIPLE DISPLAY; FOREIGN PEPTIDES; VACCINE DESIGN; ANTIBODIES; PHAGE; SEQUENCE; DNA AB The principal neutralizing determinant of the human immunodeficiency virus type 1 (HIV-1) is an intra-chain disulphide-bridged loop, designated V3, in the third hypervariable region of the surface glycoprotein gp 120. Peptide sequences from the V3 loop of gp 120 from HIV-1 strain MN (HIV-1(MX)) were engineered into the N-terminal region of the major coat protein of filamentous bacteriophage fd, leading to their display in multiple copies on the surface of the bacteriophage virion. Peptides displayed in this way were shown to be remarkably effective structural mimics of the natural epitope. They were recognised by human HIV antisera and evoked high titres of antibodies in mice, which cross-reacted with other strains of HIV and were capable of neutralizing the virus. In addition, antibody production could be stimulated by simultaneous inoculation with T-cell epitopes similarly displayed on filamentous bacteriophage. The bacteriophage display system offers a powerful means of studying the immunological recognition of proteins and is a promising vaccine model. C1 UNIV CAMBRIDGE,DEPT BIOCHEM,CAMBRIDGE CTR MOLEC RECOGNIT,CAMBRIDGE CB2 1QW,ENGLAND. ADV BIOSCI LABS INC,KENSINGTON,MD 20895. NCI,CELL BIOL LAB,BETHESDA,MD 20892. NR 34 TC 55 Z9 57 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 OCT 21 PY 1994 VL 243 IS 2 BP 167 EP 172 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PM988 UT WOS:A1994PM98800004 ER PT J AU HAYES, F AUSTIN, S AF HAYES, F AUSTIN, S TI TOPOLOGICAL SCANNING OF THE P1 PLASMID PARTITION SITE SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE PLASMID; PARTITION; PARS; IHF; TOPOLOGY ID INTEGRATION HOST FACTOR; FINE-STRUCTURE ANALYSIS; ESCHERICHIA-COLI; BACTERIOPHAGE-LAMBDA; BINDING ACTIVITY; PARB PROTEIN; IHF PROTEIN; DNA; RECOMBINATION; SPECIFICITY AB The parS site of the P1 plasmid promotes active partition of P1 to daughter cells when the P1 ParA and ParB proteins are provided. The structure of parS was modified by substituting portions of the sequence with synthetic oligonucleotides and testing partition activity of the resulting mutants in an in vivo assay The boundaries of the site were defined. They enclose a 74 bp region with a central integration host factor (IHF) binding region flanked by two arms containing heptamer and hexamer ParB binding motifs. The IHF binding region was shown to be important for partition activity but could be replaced by sequences containing A tracts that induce static bends in the DNA. The properties of sites with spacer sequences of different lengths inserted at one of five different locations led to the following conclusions. (1) The spacing between the heptamer and hexamer ParB binding motifs in both arms is critical for function. (2) Optimum partition activity requires that the parS site arms are bent toward each other with specific faces of the two helices facing each other. (3) Both arms show torsional rigidity in the active complex. (4) The left arm is laterally inflexible and activity is lost when it is extended unless the right arm is similarly extended. (5) The right arm is laterally flexible so that, when it is extended by an integral number of turns of the helix, it can still align properly with a left arm of wild-type length. The results suggest that right-arm flexibility is promoted by an A + T-rich region that is essential for II-IF binding and lies adjacent to the IHF binding consensus motif. Inherent flexibility of this A + T-rich region also appears to account for the residual activity of parS sites in which the IHF binding consensus has been destroyed by multiple point mutations. The results are consistent with a proposed structure in which specific alignment of the parS site arms by an IHF-promoted bend allows them to be linked by bifunctional ParB protein binding. We suggest that such a structure might be involved in the specific pairing and unpairing of daughter plasmids during partition by an isomerization reaction. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 33 TC 36 Z9 36 U1 1 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD OCT 21 PY 1994 VL 243 IS 2 BP 190 EP 198 DI 10.1006/jmbi.1994.1646 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PM988 UT WOS:A1994PM98800007 PM 7932749 ER PT J AU HALLOCK, YF MANFREDI, KP BLUNT, JW CARDELLINA, JH SCHAFFER, M GULDEN, KP BRINGMANN, G LEE, AY CLARDY, J FRANCOIS, G BOYD, MR AF HALLOCK, YF MANFREDI, KP BLUNT, JW CARDELLINA, JH SCHAFFER, M GULDEN, KP BRINGMANN, G LEE, AY CLARDY, J FRANCOIS, G BOYD, MR TI KORUPENSAMINES-A-D, NOVEL ANTIMALARIAL ALKALOIDS FROM ANCISTROCLADUS-KORUPENSIS SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID ACETOGENIC ISOQUINOLINE ALKALOIDS; ABSOLUTE-CONFIGURATION; ABBREVIATUS AB Four novel C5/C8'-linked naphthyltetrahydroisoquinolines 1-4, named korupensamines A-D, along with the tetrahydroisoquinoline 5, were isolated from extracts of the tropical liana Ancistrocladus korupensis. The structures of these alkaloids were solved by extensive spectroscopic analyses, particularly HMQC, HMBC, and difference NOE NMR experiments. The absolute configuration of korupensamine A was initially deduced from X-ray crystallographic analysis of the p-bromobenzenesulfonate derivative 6 and later confirmed by chemical degradation of 1 to known amino acids. Chemical degradation also established the absolute configuration of the whole series 1-5. The related dimeric compounds, michellamines A, B, and C, previously reported from the same plant, are active against HIV-1 and HIV-2; however, the ''monomeric'' compounds reported herein are essentially inactive against HIV. In contrast, the ''monomers'' 1 and 2 are active in vitro against malaria parasites Plasmodium falciparum and P. berghei, whereas the michellamines exhibit only very weak antimalarial activity. C1 UNIV WURZBURG,INST ORGAN CHEM,D-97074 WURZBURG,GERMANY. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21072. CORNELL UNIV,BAKER LAB,DEPT CHEM,ITHACA,NY 14853. INST TROP GENEESKUNDE,PROTOZOOL LAB,B-2000 ANTWERP,BELGIUM. OI Blunt, John/0000-0003-4053-4376 NR 15 TC 126 Z9 126 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 OCT 21 PY 1994 VL 59 IS 21 BP 6349 EP 6355 DI 10.1021/jo00100a042 PG 7 WC Chemistry, Organic SC Chemistry GA PN674 UT WOS:A1994PN67400042 ER PT J AU BAI, X MASCARELLA, SW BOWEN, WD CARROLL, FI AF BAI, X MASCARELLA, SW BOWEN, WD CARROLL, FI TI A NOVEL ASYMMETRIC-SYNTHESIS OF 3-BENZYL-1,2,3,4,5,6-HEXAHYDRO-11-ALKYL-2,6-METHANO-3-BENZAZOCINES SO JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS LA English DT Article ID RECEPTORS; SIGMA; NAPHTHALENES; ADDITIONS AB 9-Alkyl 6,7-benzomorphans (1,2,3,4,5,6-hexahydro-11-alkyl-2,6-methano-3-benzazocines) are important selective ligands of sigma receptor sites; their asymmetric synthesis starting with (1R,2R)- or (1S,2S)-1-hydroxymethyl-2-alkyl-1,2-dihydronaphthalene is described. C1 RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NIDDK,MED CHEM LAB,BETHESDA,MD 20892. NR 11 TC 3 Z9 3 U1 0 U2 0 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK MILTON ROAD, CAMBRIDGE, CAMBS, ENGLAND CB4 4WF SN 0022-4936 J9 J CHEM SOC CHEM COMM JI J. Chem. Soc.-Chem. Commun. PD OCT 21 PY 1994 IS 20 BP 2401 EP 2402 DI 10.1039/c39940002401 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA PN869 UT WOS:A1994PN86900043 ER PT J AU TALKAD, VD PATTO, RJ METZ, DC TURNER, RJ FORTUNE, KP BHAT, ST GARDNER, JD AF TALKAD, VD PATTO, RJ METZ, DC TURNER, RJ FORTUNE, KP BHAT, ST GARDNER, JD TI CHARACTERIZATION OF THE 3 DIFFERENT STATES OF THE CHOLECYSTOKININ (CCK) RECEPTOR IN PANCREATIC ACINI SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE CHOLECYSTOKININ; RECEPTOR; KINETICS; (PANCREAS) ID GUINEA-PIG PANCREAS; DISPERSED ACINI; AMYLASE RELEASE; CELLS; SECRETION; PEPTIDE; RAT AB By measuring binding of [I-125]CCK-8 and [H-3]L-364,718 to rat pancreatic acini we demonstrated directly that the pancreatic CCK receptor can exist in three different affinity states with respect to CCK - high affinity, low affinity and very low affinity. Binding of [I-125]CCK-8 reflects interaction of the tracer with the high and low affinity states, whereas binding of [H-3]L-364,718 reflects interaction of the tracer with the low and very low affinity states. Treating acini with carbachol abolished the high affinity state of the CCK receptor and converted approximately 25% of the low affinity receptors to the very low affinity state. Carbachol treatment was particularly useful in establishing the values of K-d for the high and low affinity states for different CCK receptor agonists and antagonists. Of the various CCK receptor agonists tested, CCK-8 had the highest affinity for the high affinity state (K-d similar to 1 nM), whereas CCK-JMV-180 had the highest affinity for the low (K-d 7 nM) and very low affinity (K-d 200 nM) states. Gastrin and de(SO4)CCK-8 had affinities for the high and low affinity states of the receptor that were 100- to 400-fold less than those of CCK-8 but had affinities for the very low affinity state that were only 3- to 10-fold less than that of CCK-8. CCK receptor antagonists showed several patterns in interacting with the different states of the CCK receptor. L-364,718 had the same affinity for each state of the CCK receptor. CR1409 and Bt(2)cGMP each had similar affinities for the high and low affinity states and lower affinity for the very low affinity state. L-365,260 and CCK-JMV-179 had the highest affinity for the low affinity state and lower affinities for the high and very low affinity states. Different CCK receptor agonists caused the same maximal stimulation of amylase secretion but showed different degrees of amplification in terms of the relationship between their abilities to stimulate amylase secretion and their abilities to occupy the low affinity state of the CCK receptor. When amplification was expressed quantitatively as the value of K-d for the low affinity state divided by the corresponding EC(50) for stimulating amylase secretion the values were CCK-8 (1000), de(SO4)CCK-8 (1500), gastrin (100) and CCK-JMV-180 (Menozzi, D., Vinayek, R., Jensen, R.T. and Gardner, J.D. (1991) J. Biol. Chem. 266, 10385-1091). Studies using carbachol-treated acini, CCK-8 and CCK-JMV-180 indicated that occupation of the low affinity state of the CCK receptor by CCK-8 or CCK-JMV-180 produces oscillations of [Ca2+](i) whereas occupation of the very low affinity state by CCK-8 causes a large, transient increase in [Ca2+](i) and this increase can be prevented by CCK-JMV-180. Thus, our results indicate that the pancreatic CCK receptor exists in three different, interconvertible affinity states for CCK-8, that each state recognizes unique structural features of various CCK receptor agonists and antagonists and that each state activates characteristic signal transduction mechanisms that, in turn, produce state-specific changes in pancreatic acinar cell function. C1 ST LOUIS UNIV,HLTH SCI CTR,DEPT INTERNAL MED,ST LOUIS,MO 63104. NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. NR 26 TC 22 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD OCT 20 PY 1994 VL 1224 IS 1 BP 103 EP 116 DI 10.1016/0167-4889(94)90118-X PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PP071 UT WOS:A1994PP07100014 PM 7524683 ER PT J AU PANDYA, PK HUANG, SC TALKAD, VD WANK, SA GARDNER, JD AF PANDYA, PK HUANG, SC TALKAD, VD WANK, SA GARDNER, JD TI BIOCHEMICAL REGULATION OF THE 3 DIFFERENT STATES OF THE CHOLECYSTOKININ (CCK) RECEPTOR IN PANCREATIC ACINI SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE CHOLECYSTOKININ; RECEPTOR; KINETICS; (PANCREAS) ID ANTAGONIST RADIOLIGAND; FUNCTIONAL EXPRESSION; RAT PANCREAS; G-PROTEINS; BINDING; CELLS; MASTOPARAN; CARBACHOL; GTP; OSCILLATIONS AB We used rat pancreatic acini and measured binding of [I-125]CCK-8 and [H-3]L-364,718 to the three different states of the CCK receptor to examine potential biochemical regulation of ligand binding for each receptor state. Binding of [I-125]CCK-8 to the high affinity state of the receptor was measured as carbachol-inhibitable binding of [I-125]CCK-8, whereas binding of [I-125]CCK-8 to the low affinity state was measured as carbachol-resistant binding of [I-125]CCK-8. Interaction of CCK-8 with the very low affinity state of the CCK receptor was measured as CCK-8-inhibitable binding of [H-3]L-364,718. [I-125]CCK-8 that was bound to the high affinity state dissociated slowly at a rate of 0.20%/min and this dissociation was not altered by 30 mM NaF. Dissociation of [I-125]CCK-8 bound to the low affinity state was biphasic - 22% of the bound radioactivity dissociated completely within 3 min and the remaining 78% dissociated slowly at a rate of 0.19%/min. Dissociation of [I-125]CCK-8 from the low affinity state was not altered by 30 mM NaF. The pattern of dissociation of bound [I-125]CCK-8 from the pancreatic CCK receptor expressed in COS cells was also biphasic and closely resembled that observed in pancreatic acini. CCK-8 that was bound to the very low affinity state dissociated completely during a 20-min period of washing and resuspension of acini that had been first incubated with CCK-8. We found extensive biochemical regulation of the different states of the CCK receptor in pancreatic acini. Bombesin, TPA, NaF, CCCP and trifluoperazine each altered binding of [I-125]CCK-8 to the high affinity state and to the low affinity state, and except for bombesin each agent was more potent in affecting the high affinity state than the low affinity state. No agent tested affected the low affinity state but not the high affinity state. In contrast, a number of agents affected the high affinity state but not the low affinity state. These included receptor-mediated agonists (carbachol, secretin, VIP), 8Br-cAMP, NEM, agents that affect microtubules or microfilaments (cytochalasin B, vinblastine), calmodulin inhibitors (W-7, chlorpromazine) and genistein. Experiments with EGTA, A23187 and thapsigargin indicated that none of the three receptor states was influenced by intracellular or extracellular calcium. No agent tested altered the interaction of CCK-8 with the very low affinity state of the CCK receptor. The effects on binding of [I-125]CCK-8 by NaF, TPA, secretin, bombesin and carbachol were enhanced by okadaic acid, indicating that the abilities of these agents to influence CCK receptor binding involves phosphorylation. The effects of TPA, but not those of NaF, secretin, bombesin or carbachol, were prevented by staurosporine and H-7 (inhibitors of protein kinase C and other kinases). Genistein (inhibitor of protein tyrosine kinase), W-7 and trifluoperazine (calmodulin antagonists) did not alter the effects of TPA, secretin, bombesin or carbachol on binding of [I-125]CCK-8. C1 ST LOUIS UNIV,HLTH SCI CTR,DEPT INTERNAL MED,ST LOUIS,MO 63104. NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. NR 36 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD OCT 20 PY 1994 VL 1224 IS 1 BP 117 EP 126 DI 10.1016/0167-4889(94)90119-8 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PP071 UT WOS:A1994PP07100015 PM 7948036 ER PT J AU POLLO, DA BALDASSARE, JJ HONDA, T HENDERSON, PA TALKAD, VD GARDNER, JD AF POLLO, DA BALDASSARE, JJ HONDA, T HENDERSON, PA TALKAD, VD GARDNER, JD TI EFFECTS OF CHOLECYSTOKININ (CCK) AND OTHER SECRETAGOGUES ON ISOFORMS OF PROTEIN-KINASE-C (PKC) IN PANCREATIC ACINI SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE CHOLECYSTOKININ; ISOZYME; PROTEIN KINASE C; ENZYME KINETICS; (PANCREAS) ID THYROTROPIN-RELEASING-HORMONE; EPIDERMAL-GROWTH-FACTOR; STIMULATES AMYLASE SECRETION; MOLECULAR-SPECIES ANALYSIS; ENZYME-SECRETION; PHORBOL ESTER; ALPHA-THROMBIN; PHOSPHATIDYLCHOLINE HYDROLYSIS; INTRACELLULAR-DISTRIBUTION; CULTURED FIBROBLASTS AB We used rat pancreatic acini and measured the effects of various agents on digestive enzyme secretion, diacylglycerol (DAG) and the cellular distribution of protein kinase C (PKC) enzyme activity as well as isoforms of PKC determined by quantitative immunoblot analysis. TPA, but not CCK-8, caused translocation of PKC enzyme activity from the cytosol fraction to the membrane fraction. Immunoblot analysis detected PKC-alpha, PKC-delta, PKC-epsilon and PKC-zeta. PKC-beta, PKC-gamma and PKC-eta were not detected. TPA caused translocation of all isoforms from cytosol to membrane, whereas CCK-8 caused translocation of PKC-delta and PKC-epsilon, carbachol caused translocation of PKC-epsilon, and bombesin and secretin caused no detectable translocation of any isoform. Specific receptor antagonists could prevent, as well as reverse completely, the translocation of PKC isoforms caused by CCK-8 or carbachol. Agonists added in sequence with an interposed addition of a specific receptor antagonist caused cycling of PKC-epsilon between cytosol and membrane fractions. Each receptor-mediated agonist that caused translocation of PKC also increased DAG, and with CCK-8 and carbachol cycling of PKC-epsilon between cytosol and membrane was accompanied by corresponding cyclic changes in cellular DAG. CCK-JMV-180, bombesin and secretin increased DAG but did not cause translocation of any PKC isoform. Translocation of a PKC isoform could be accounted for by whether the increased DAG originated from PIP2 (accompanied by translocation) or from phosphatidylcholine (no accompanying translocation). Thus it appeared that DAG, in pancreatic acini, is functionally compartmentalized depending on the source of the lipid. Studies using CCK-8 and CCK-JMV-180 indicated that occupation of the low affinity state of the CCK receptor by either peptide increased DAG from phosphatidylcholine, whereas occupation of the very low affinity state by CCK-8 increased DAG from PIP2 and caused translocation of PKC-delta and PKC-epsilon. TPA stimulated amylase secretion, indicating that activation of PKC can stimulate enzyme secretion; however, with the various receptor-mediated secretagogues there was no consistent, unequivocal correlation between translocation of an isoform of PKC and accompanying changes in enzyme secretion. C1 NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. RP POLLO, DA (reprint author), ST LOUIS UNIV,HLTH SCI CTR,DEPT INTERNAL MED,1402 S GRAND BLVD,ST LOUIS,MO 63104, USA. NR 65 TC 45 Z9 46 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD OCT 20 PY 1994 VL 1224 IS 1 BP 127 EP 138 DI 10.1016/0167-4889(94)90120-1 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PP071 UT WOS:A1994PP07100016 PM 7524684 ER PT J AU LEE, JW LEWIN, NE BLUMBERG, PM MARQUEZ, VE AF LEE, JW LEWIN, NE BLUMBERG, PM MARQUEZ, VE TI CONFORMATIONALLY CONSTRAINED ANALOGS OF DIACYLGLYCEROL .9. THE EFFECT OF SIDE-CHAIN ORIENTATION ON THE PROTEIN-KINASE-C (PK-C) BINDING-AFFINITY OF DELTA-LACTONES SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID GAMMA-LACTONES; ISOENZYMES; FAMILY; DAG AB The construction of conformationally constrained diacylglycerol analogues on an alpha-alkylidene-delta-lactone template was achieved stereospecifically from L-xylose. The increased PK-C binding affinity of the E-isomer (6) over the Z-isomer (5) contrasts with the more modest difference observed for the same geometrical isomers built on an alpha-alkylidene-gamma-lactone template. The more effective discrimination between isomeric alpha-alkylidene-delta-lactones by PK-C forcefully argues that orientation of the side-chain is a key determinant for a strong interaction with the enzyme. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,MOLEC TUMOR PROMOT SECT,BETHESDA,MD 20892. NR 15 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 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD OCT 20 PY 1994 VL 4 IS 20 BP 2405 EP 2410 DI 10.1016/S0960-894X(01)80399-1 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA PQ057 UT WOS:A1994PQ05700007 ER PT J AU ENSOLI, B GENDELMAN, R MARKHAM, P FIORELLI, V COLOMBINI, S RAFFELD, M CAFARO, A CHANG, HK BRADY, JN GALLO, RC AF ENSOLI, B GENDELMAN, R MARKHAM, P FIORELLI, V COLOMBINI, S RAFFELD, M CAFARO, A CHANG, HK BRADY, JN GALLO, RC TI SYNERGY BETWEEN BASIC FIBROBLAST GROWTH-FACTOR AND HIV-I TAT PROTEIN IN INDUCTION OF KAPOSIS-SARCOMA SO NATURE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; MELANOMA CELL INVASION; LONG-TERM CULTURE; GENE-EXPRESSION; ENDOTHELIAL-CELLS; BASEMENT-MEMBRANE; HTLV-III; AIDS; ANGIOGENESIS; COLLAGENASE AB Basic fibroblast growth factor (bFGF) and human immunodeficiency virus type 1 (HIV-1) Tat protein synergize in inducing angiogenic Kaposi's sarcoma-like lesions in mice. Synergy is due to Tat, which enhances endothelial cell growth and type-IV collagenase expression in response to bFGF mimicking extracellular matrix proteins. The bFGF, extracellular Tat and Tat receptors are present in HIV-1-associated KS, which may explain the higher frequency and aggressiveness of this form compared to classical Kaposi's sarcoma where only bFGF is present. C1 NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. ADV BIOSCI LABS INC,KENSINGTON,MD 20895. HENRY M JACKSON FDN,ROCKVILLE,MD 20850. RP ENSOLI, B (reprint author), NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892, USA. RI Ensoli, Barbara/J-9169-2016; Cafaro, Aurelio/K-5314-2016 OI Ensoli, Barbara/0000-0002-0545-8737; NR 43 TC 480 Z9 483 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 OCT 20 PY 1994 VL 371 IS 6499 BP 674 EP 680 DI 10.1038/371674a0 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PM773 UT WOS:A1994PM77300047 PM 7935812 ER PT J AU VAJANAPHANICH, M SCHULTZ, C RUDOLF, MT WASSERMAN, M ENYEDI, P CRAXTON, A SHEARS, SB TSIEN, RY BARRETT, KE TRAYNORKAPLAN, A AF VAJANAPHANICH, M SCHULTZ, C RUDOLF, MT WASSERMAN, M ENYEDI, P CRAXTON, A SHEARS, SB TSIEN, RY BARRETT, KE TRAYNORKAPLAN, A TI LONG-TERM UNCOUPLING OF CHLORIDE SECRETION FROM INTRACELLULAR CALCIUM LEVELS BY INS(3,4,5,6)P-4 SO NATURE LA English DT Article ID EPITHELIAL-CELL LINE; INOSITOL TETRAKISPHOSPHATE; RAT-LIVER; PURIFICATION; PHOSPHATES; TRANSPORT AB OSMOREGULATION, inhibitory neurotransmission and pH balance depend on chloride ion (Cl-) flux. In intestinal epithelial cells, apical Cl- channels control salt and fluid secretion and are, in turn, regulated by agonists acting through cyclic nucleotides and internal calcium ion concentration ([Ca2+](i))(1-3). Recently, we found that muscarinic pretreatment prevents [Ca2+](i) increases from eliciting Cl- secretion in T-84 colonic epithelial cells(4). By studying concomitant inositol phosphate metabolism, ae have now identified D-myo-inositol 3,4,5,6-tetrakisphosphate (Ins(3,4,5,6)P-4), as the inositol phosphate most likely to mediate this uncoupling. A novel, membrane-permeant ester prepared by total synthesis delivers Ins(3,4,5,6)P-4 intracellularly and confirms that this emerging messenger(5) does inhibit Cl- flux resulting from thapsigargin- or histamine-induced [Ca2+](i) elevations. C1 UNIV CALIF SAN DIEGO,SCH MED,DEPT MED 8414,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,SCH MED,DEPT PHARMACOL,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,SCH MED,HOWARD HUGHES MED INST,LA JOLLA,CA 92093. UNIV BREMEN,INST ORGAN CHEM,W-2800 BREMEN,GERMANY. NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709. OI Schultz, Carsten/0000-0002-5824-2171 NR 20 TC 154 Z9 153 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 OCT 20 PY 1994 VL 371 IS 6499 BP 711 EP 714 DI 10.1038/371711a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PM773 UT WOS:A1994PM77300059 PM 7935818 ER PT J AU SMITH, EP BOYD, J FRANK, GR TAKAHASHI, H COHEN, RM SPECKER, B WILLIAMS, TC LUBAHN, DB KORACH, KS AF SMITH, EP BOYD, J FRANK, GR TAKAHASHI, H COHEN, RM SPECKER, B WILLIAMS, TC LUBAHN, DB KORACH, KS TI ESTROGEN RESISTANCE CAUSED BY A MUTATION IN THE ESTROGEN-RECEPTOR GENE IN A MAN SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ANDROGEN INSENSITIVITY; AROMATASE DEFICIENCY; MEN; OSTEOPOROSIS; HYPOGONADISM; CONSEQUENCES; PUBERTY; FEMALE; MICE AB Background and Methods. Mutations in the estrogen-receptor gene have been thought to be lethal. A 28-year-old man whose estrogen resistance was caused by a disruptive mutation in the estrogen-receptor gene underwent studies of pituitary-gonadal function and bone density and received transdermal estrogen for six months. Estrogen-receptor DNA, extracted from lymphocytes, was evaluated by analysis of single-strand-conformation polymorphisms and by direct sequencing. Results. The patient was tall (204 cm [80.3 in.]) and had incomplete epiphyseal closure, with a history of continued linear growth into adulthood despite otherwise normal pubertal development. He was normally masculinized and had bilateral axillary acanthosis nigricans. Serum estradiol and estrone concentrations were elevated, and serum testosterone concentrations were normal. Serum follicle-stimulating hormone and luteinizing hormone concentrations were increased. Glucose tolerance was impaired, and hyperinsulinemia was present. The bone mineral density of the lumbar spine was 0.745 g per square centimeter, 3.1 SD below the mean for age-matched normal women; there was biochemical evidence of increased bone turnover. The patient had no detectable response to estrogen administration, despite a 10-fold increase in the serum free estradiol concentration. Conformation analysis of his estrogen-receptor gene revealed a variant banding pattern in exon 2. Direct sequencing of exon 2 revealed a cytosine-to-thymine transition at codon 157 of both alleles, resulting in a premature stop codon. The patient's parents were heterozygous carriers of this mutation, and pedigree analysis revealed consanguinity. Conclusions. Disruption of the estrogen receptor in humans need not be lethal. Estrogen is important for bone maturation and mineralization in men as well as women. C1 UNIV CINCINNATI,CHILDRENS HOSP,COLL MED,MED CTR,DIV NEONATOL,CINCINNATI,OH. UNIV CINCINNATI,COLL MED,DEPT INTERNAL MED,DIV ENDOCRINOL,CINCINNATI,OH. UNIV N CAROLINA,SCH MED,DEPT PEDIAT,CHAPEL HILL,NC. UNIV N CAROLINA,SCH MED,DEPT PATHOL,CHAPEL HILL,NC. NIEHS,RECEPTOR BIOL SECT,RES TRIANGLE PK,NC. RP SMITH, EP (reprint author), UNIV CINCINNATI,CHILDRENS HOSP,COLL MED,MED CTR,DEPT PEDIAT,DIV ENDOCRINOL,3333 BURNETT AVE,CINCINNATI,OH 45229, USA. OI Korach, Kenneth/0000-0002-7765-418X; Specker, Bonny/0000-0003-4759-9957 FU NCRR NIH HHS [MO1 RR 08084] NR 31 TC 1581 Z9 1622 U1 5 U2 29 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 OCT 20 PY 1994 VL 331 IS 16 BP 1056 EP 1061 DI 10.1056/NEJM199410203311604 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA PL560 UT WOS:A1994PL56000004 PM 8090165 ER PT J AU SILBERMAN, G CROSSE, MG PETERSON, EA WESTON, RC HOROWITZ, MM APPELBAUM, FR CHESON, BD AF SILBERMAN, G CROSSE, MG PETERSON, EA WESTON, RC HOROWITZ, MM APPELBAUM, FR CHESON, BD TI AVAILABILITY AND APPROPRIATENESS OF ALLOGENEIC BONE-MARROW TRANSPLANTATION FOR CHRONIC MYELOID-LEUKEMIA IN 10 COUNTRIES SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; T-CELL DEPLETION; INCREASING UTILIZATION; CHRONIC PHASE; DONORS AB Background. Allogeneic bone marrow transplantation, a sophisticated and expensive procedure, is the only curative therapy for chronic myeloid leukemia (CML). We examined the availability and appropriateness of allogeneic bone marrow transplantation for CML in 10 economically advanced countries with diverse health care systems. For each country we obtained data on the likelihood of transplantation to treat CML in patients under the age of 55 years, the length of time from diagnosis to transplantation, and the stage of disease at the time of transplantation. Methods. Data were collected on 9873 allogeneic bone marrow transplantations performed at 208 centers in 10 countries from 1989 th rough 1991. Data were acquired from transplantation registries and by means of a mailed survey of all centers and teams that did not contribute data to registries. Data on the incidence of disease were drawn from national and regional cancer registries. Results. Among the 10 countries there was a twofold difference between the lowest and highest rates of transplantation to treat CML (0.26 to 0.54 per 100,000 population per year); Swedish patients were the most likely to receive a transplant, and German patients the least likely. The median length of time from diagnosis to transplantation ranged from 6.8 to 15.4 months. In all countries, most transplantations were performed in the chronic phase of the disease, but as many as a third of patients received transplants in the less favorable accelerated or blast phase. The values for the United States fell near the middle of those for the 10 countries on all measures. Conclusions. Our findings challenge the assumption that the United States is unique in providing broad access to high-technology treatments. On no measure of the availability or appropriateness of transplantation for CML did it surpass the other nine countries studied. C1 MED COLL WISCONSIN,INST HLTH POLICY,INT BONE MARROW TRANSPLANT REGISTRY,MILWAUKEE,WI. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA. NCI,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD. RP SILBERMAN, G (reprint author), US GEN ACCOUNTING OFF,DIV PROGRAM EVALUAT & METHODOL,WASHINGTON,DC 20548, USA. FU NCI NIH HHS [P01-CA-40053] NR 20 TC 45 Z9 45 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 OCT 20 PY 1994 VL 331 IS 16 BP 1063 EP 1067 DI 10.1056/NEJM199410203311606 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA PL560 UT WOS:A1994PL56000006 PM 8090167 ER PT J AU ATKINSON, RL DIETZ, WH FOREYT, JP GOODWIN, NJ HILL, JO HIRSCH, J PISUNYER, FX WEINSIER, RL WING, R HOOFNAGLE, JH EVERHART, J HUBBARD, VS YANOVSKI, SZ AF ATKINSON, RL DIETZ, WH FOREYT, JP GOODWIN, NJ HILL, JO HIRSCH, J PISUNYER, FX WEINSIER, RL WING, R HOOFNAGLE, JH EVERHART, J HUBBARD, VS YANOVSKI, SZ TI WEIGHT CYCLING SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID RESTING METABOLIC-RATE; BODY-WEIGHT; VISCERAL FAT; OBESE WOMEN; RISK FACTOR; CARDIOVASCULAR-DISEASE; ANTHROPOMETRIC CHANGES; FOOD RESTRICTION; FOLLOW-UP; REGAIN AB Objective.-To address concerns about the effects of weight cycling and to provide guidance on the risk-to-benefit ratio of attempts at weight loss, given current scientific knowledge. Data Sources.-Original reports obtained through MEDLINE and psychological abstracts searches for 1966 through 1994 on weight cycling, ''yo-yo dieting,'' and weight fluctuation,supplemented by a manual search of bibliographies. Study Selection.-English-language articles that evaluated the effects of weight change or weight cycling on humans or animals. Data Extraction.-Studies were reviewed by experts in the fields of nutrition, obesity, and epidemiology to evaluate study design and the-validity of the authors' conclusions based on published data. Data Synthesis.-The majority of studies do not support an adverse effect of weight cycling on metabolism. Many observational studies have shown an association between variation in body weight and increased morbidity and mortality. However, most of these studies did not examine intentional vs unintentional weight loss, nor were they designed to determine the effects of weight cycling in obese, as opposed to normal-weight, individuals. Conclusions.-The currently available evidence is not sufficiently compelling to override the potential benefits of moderate weight loss in significantly obese patients. Therefore, obese individuals should not allow concerns about hazards of weight cycling to deter them from efforts to control their body weight. Although conclusive data regarding long-term health effects of weight cycling are lacking, nonobese individuals should attempt to maintain a stable weight. Obese individuals who undertake weight loss efforts should be ready to commit to lifelong changes in their behavioral patterns, diet, and physical activity. C1 NIDDK,DIV DIGEST DIS & NUTR,BETHESDA,MD 20892. UNIV WISCONSIN,MADISON,WI. TUFTS UNIV,SCH MED,BOSTON,MA 02111. BAYLOR COLL MED,HOUSTON,TX 77030. HLTH WATCH,INFORMAT & PROMOT SERV,NEW YORK,NY. UNIV COLORADO,DENVER,CO 80202. ROCKEFELLER UNIV,NEW YORK,NY 10021. COLUMBIA UNIV,ST LUKES ROOSEVELT HOSP CTR,NEW YORK,NY. UNIV ALABAMA,BIRMINGHAM,AL. UNIV PITTSBURGH,SCH MED,PITTSBURGH,PA. OI Atkinson, Richard L./0000-0003-1745-5645 NR 75 TC 117 Z9 119 U1 0 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 19 PY 1994 VL 272 IS 15 BP 1196 EP 1202 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA PL212 UT WOS:A1994PL21200034 ER PT J AU AARON, AD AF AARON, AD TI THE MANAGEMENT OF CANCER METASTATIC TO BONE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID BREAST-CANCER; CARCINOMA; ETIDRONATE; PALLIATION; INVASION; PROSTATE; GROWTH C1 NIAMS,BETHESDA,MD. RP AARON, AD (reprint author), GEORGETOWN UNIV HOSP,DEPT ORTHOPED SURG,3800 RESERVOIR RD NW,PHC-G,WASHINGTON,DC 20007, USA. NR 29 TC 68 Z9 71 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 OCT 19 PY 1994 VL 272 IS 15 BP 1206 EP 1209 DI 10.1001/jama.272.15.1206 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA PL212 UT WOS:A1994PL21200036 PM 7933350 ER PT J AU NIGHTINGALE, TE GRUBER, J AF NIGHTINGALE, TE GRUBER, J TI HELICOBACTER AND HUMAN CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CELL GASTRIC LYMPHOMA; ANIMAL-MODEL; PYLORI; CARCINOMA; ERADICATION; INFECTION; MUSTELAE; FERRET; TISSUE; IMMUNIZATION C1 NCI,DIV CANC ETIOL,BIOL CARCINOGENESIS BRANCH,BETHESDA,MD 20892. NR 37 TC 13 Z9 13 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 OCT 19 PY 1994 VL 86 IS 20 BP 1505 EP 1509 DI 10.1093/jnci/86.20.1505 PG 5 WC Oncology SC Oncology GA PL354 UT WOS:A1994PL35400007 PM 7932804 ER PT J AU SILVERMAN, DT DUNN, JA HOOVER, RN SCHIFFMAN, M LILLEMOE, KD SCHOENBERG, JB BROWN, LM GREENBERG, RS HAYES, RB SWANSON, GM WACHOLDER, S SCHWARTZ, AG LIFF, JM POTTERN, LM AF SILVERMAN, DT DUNN, JA HOOVER, RN SCHIFFMAN, M LILLEMOE, KD SCHOENBERG, JB BROWN, LM GREENBERG, RS HAYES, RB SWANSON, GM WACHOLDER, S SCHWARTZ, AG LIFF, JM POTTERN, LM TI CIGARETTE-SMOKING AND PANCREAS CANCER - A CASE-CONTROL STUDY BASED ON DIRECT INTERVIEWS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PAST MEDICAL HISTORY; RISK-FACTORS; BEVERAGE CONSUMPTION; COFFEE CONSUMPTION; ALCOHOL; TOBACCO; DIET; MORTALITY; CARCINOMA; INDUCTION AB Background: Cigarette smoking is the most consistently reported risk factor for pancreas cancer, yet the dose-response relationship in many pancreas cancer studies is weak. Because of the poor prognosis for pancreas cancer, many case-control studies have been based largely on interviews with proxy respondents, who are known to report less reliable information on detailed smoking habits than original subjects. Purpose: Our purpose was to evaluate cigarette smoking as a risk factor for pancreas cancer based on data obtained only from direct interviews and to estimate the effects of quitting smoking and of switching from nonfiltered to filtered cigarettes on risk. Our objective also was to estimate the contribution of cigarette smoking toward explaining the higher pancreas cancer incidence experienced by black Americans compared with white Americans. Methods: A population-based, case-control study of pancreas cancer was conducted during 1986-1989 in Atlanta, Ga., Detroit, Mich., and 10 counties in New Jersey. Direct interviews were successfully completed with 526 case patients and 2153 control subjects aged 30-79 years, making this the largest population-based, case-control study of pancreas cancer to date based only on direct interviews. Results: Cigarette smokers had a significant, 70% increased risk of pancreas cancer compared with the risk in nonsmokers. A significant, positive trend in risk with increasing duration smoked was apparent (P<.0001), with long-term (greater than or equal to 40 years) smokers experiencing a modest 2.1-fold risk. We also observed a negative trend in risk with increasing years quit smoking. Smokers who quit for more than 10 years experienced about a 30% reduction in risk relative to current smokers; quitters of 10 years or less experienced no risk reduction. Switching from nonfiltered to filtered cigarettes did not appear to decrease risk. Compared with nonsmokers, subjects who smoked only filtered cigarettes had a 50% elevated risk and those who smoked only nonfiltered cigarettes had a 40% elevated risk. The proportion of pancreas cancer attributable to cigarette smoking was 29% in blacks and 26% in whites. Conclusions: The relationship between cigarette smoking and pancreas cancer risk is likely to be causal, despite the weakness of the dose-response data. Long-term smoking cessation clearly reduces risk, whereas switching from nonfiltered to filtered cigarettes may not be beneficial. Cigarette smoking appears to explain little of the excess pancreas cancer risk experienced by blacks. Implications: Elimination of cigarette smoking would eventually prevent approximately 27% of pancreas cancer, saving 6750 lives in the United States annually. C1 UNIV BIRMINGHAM,CANC RES CAMPAIGN,TRIALS UNIT,BIRMINGHAM,W MIDLANDS,ENGLAND. JOHNS HOPKINS UNIV,SCH MED,DEPT SURG,BALTIMORE,MD 21205. NEW JERSEY STATE DEPT HLTH,SPECIAL EPIDEMIOL PROGRAM,TRENTON,NJ. EMORY UNIV,SCH PUBL HLTH,DIV EPIDEMIOL,ATLANTA,GA. MICHIGAN STATE UNIV,COLL HUMAN MED,E LANSING,MI 48824. UNIV PITTSBURGH,SCH MED,DEPT CLIN EPIDEMIOL & FAMILY MED,PITTSBURGH,PA. RP SILVERMAN, DT (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,RM 415,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01CP51092, N01CP51089, N01CP51090] NR 36 TC 195 Z9 199 U1 1 U2 4 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 19 PY 1994 VL 86 IS 20 BP 1510 EP 1516 DI 10.1093/jnci/86.20.1510 PG 7 WC Oncology SC Oncology GA PL354 UT WOS:A1994PL35400008 PM 7932805 ER PT J AU CHU, KC TARONE, RE AF CHU, KC TARONE, RE TI TEMPORAL PATTERNS IN COLORECTAL-CANCER INCIDENCE, SURVIVAL, AND MORTALITY FROM 1950 THROUGH 1990 - REPLY SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; UNITED-STATES; DIETARY-FAT; TRENDS; CONSUMPTION C1 NCI,DIV CANC ETIOL,BIOSTAT BRANCH,BETHESDA,MD 20892. RP CHU, KC (reprint author), NCI,DIV CANC PREVENT & CONTROL,SPECIAL POPULAT STUDIES BRANCH,6130 EXECUT BLVD,EXECUT PLAZA N,BETHESDA,MD 20892, USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 19 PY 1994 VL 86 IS 20 BP 1555 EP 1556 DI 10.1093/jnci/86.20.1555 PG 2 WC Oncology SC Oncology GA PL354 UT WOS:A1994PL35400017 ER PT J AU BLAIR, A STEWART, PA AF BLAIR, A STEWART, PA TI MISCLASSIFICATION OF NASOPHARYNGEAL CANCER - REPLY SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI,DIV CANC ETIOL,ENVIRONM & BIOSTAT PROGRAM,ENVIRONM EPIDEMIOL BRANCH,OCCUPAT STUDIES SECT,BETHESDA,MD 20892. NR 2 TC 1 Z9 1 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 19 PY 1994 VL 86 IS 20 BP 1557 EP 1558 DI 10.1093/jnci/86.20.1557-a PG 2 WC Oncology SC Oncology GA PL354 UT WOS:A1994PL35400019 ER PT J AU UCHIDA, K TOYOKUNI, S NISHIKAWA, K KAWAKISHI, S ODA, H HIAI, H STADTMAN, ER AF UCHIDA, K TOYOKUNI, S NISHIKAWA, K KAWAKISHI, S ODA, H HIAI, H STADTMAN, ER TI MICHAEL ADDITION-TYPE 4-HYDROXY-2-NONENAL ADDUCTS IN MODIFIED LOW-DENSITY LIPOPROTEINS - MARKERS FOR ATHEROSCLEROSIS SO BIOCHEMISTRY LA English DT Article ID ENHANCED MACROPHAGE DEGRADATION; METAL-CATALYZED OXIDATION; MIXED-FUNCTION OXIDATION; SMOOTH-MUSCLE CELLS; LIPID-PEROXIDATION; GLUTAMINE-SYNTHETASE; POSSIBLE INVOLVEMENT; ENDOTHELIAL-CELLS; PROTEIN ADDUCTS; INACTIVATION AB It has been proposed that plasma low-density lipoprotein (LDL) undergoes oxidative modification before it can give rise to foam cells in atherosclerosis. Oxidation of LDL generates a variety of reactive aldehyde products including 4-hydroxy-2-nonenal (HNE), which may covalently attach to the LDL apolipoproteins. We here present direct evidence that HNE derivatization of LDL forms Michael addition-type adducts of HNE with histidine and lysine residues of apolipoprotein B-100 (apo B) and also demonstrate the utility of an antibody specific to the HNE adducts generated in the LDL treated with HNE or oxidatively modified by CU2+ Or cultured endothelial cells. HNE adducts present in the LDL that had been treated with HNE were attested to be Michael addition-type adducts on the basis of the fact that incubation of LDL with 1 mM HNE (2 h, 37 degrees C) resulted primarily in the formation of Michael addition-type HNE-histidine (39.9 mol/mol of LDL) and HNE-lysine (19.3 mol/mol of LDL) adducts. An enzyme-linked immunosorbent assay (ELISA) and an SDS-polyacrylamide gel electrophoresis (SDS-PAGE)/immunoblot analysis of HNE-modified LDL demonstrated that these HNE adducts were detectable with the HNE-specific antibody affinity-purified with the Michael adduct (HNE-histidine) as a ligand. The following lines of evidence indicated the presence of Michael addition-type HNE adducts in the oxidatively modified LDL in vitro: (i) Amino acid analysis of LDL that had been treated with CU2+ (24 h, 37 degrees C) demonstrated the presence of a Michael addition-type HNE-histidine adduct (7-9 mol/mol of LDL). (ii) Competitive ELISA demonstrated the inhibition of antibody binding to HNE-modified LDL by the addition of Cu2+ oxidized LDL. (iii) SDS-PAGE/immunoblot analysis of the Cu2+-oxidized LDL demonstrated the appearance of HNE adducts, which were abolished by the addition of a HNE-modified histidyl peptide. Furthermore, HNE adducts were detected in the LDL that had been treated with cultured bovine aortic endothelial cells (24 h, 37 degrees C), Taken together, this evidence suggests that the Michael addition-type HNE adducts may be reliable markers for atherosclerosis. C1 KYOTO UNIV,FAC MED,DEPT PATHOL,SAKYO KU,KYOTO 606,JAPAN. NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NAGOYA UNIV,SCH AGR,NUTR BIOCHEM LAB,NAGOYA,AICHI 46401,JAPAN. RP UCHIDA, K (reprint author), NAGOYA UNIV,SCH AGR,FOOD & BIODYNAM LAB,NAGOYA,AICHI 46401,JAPAN. RI Toyokuni, Shinya/C-1358-2010 OI Toyokuni, Shinya/0000-0002-5757-1109 NR 51 TC 200 Z9 201 U1 0 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 18 PY 1994 VL 33 IS 41 BP 12487 EP 12494 DI 10.1021/bi00207a016 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PM582 UT WOS:A1994PM58200016 PM 7918471 ER PT J AU MURPHY, LD ZIMMERMAN, SB AF MURPHY, LD ZIMMERMAN, SB TI MACROMOLECULAR CROWDING EFFECTS ON THE INTERACTION OF DNA WITH ESCHERICHIA-COLI DNA-BINDING PROTEINS - A MODEL FOR BACTERIAL NUCLEOID STABILIZATION SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE DNA; DNA-BINDING PROTEIN; HU; MACROMOLECULAR CROWDING; NUCLEOID; (ESCHERICHIA-COLI) ID HISTONE-LIKE PROTEINS; HU-PROTEIN; YEAST MITOCHONDRIA; PROKARYOTIC DNA; INVIVO; RENATURATION; RECOGNITION; POLYMERASE; CYTOPLASM; INVITRO AB DNA-binding protein fractions from exponential and stationary phase cell extracts of E. coli were isolated by affinity chromatography on native DNA-cellulose. The ability of these fractions to convert DNA into a readily-sedimented form was compared in the absence or presence of added polymers. In the absence of polymers, large amounts of the proteins were required. In the presence of polyethylene glycol or polyvinylpyrrolidone, much smaller amounts of the DNA-binding proteins were required, indicating a macromolecular crowding effect from these polymers. The enhanced binding under crowded conditions appears to resolve a paradox between the cellular abundance of the DNA-binding proteins and the amounts required in earlier in vitro studies. The 'histone-like' protein HU from the DNA-binding protein fraction was preferentially incorporated into the pelleted DNA in the presence of polymers. Purified HU at roughly similar amounts caused a similar conversion of DNA to a readily-sedimentable ('condensed') form. Crowding-enhancement of DNA condensation by promoting the binding of proteins to the DNA provides a model for the stabilization of systems such as the bacterial nucleoid or kinetoplast DNA. C1 NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 53 TC 56 Z9 57 U1 3 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD OCT 18 PY 1994 VL 1219 IS 2 BP 277 EP 284 DI 10.1016/0167-4781(94)90049-3 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PN104 UT WOS:A1994PN10400004 PM 7918622 ER PT J AU STRAUSS, KI ISAACS, KR HA, QN JACOBOWITZ, DM AF STRAUSS, KI ISAACS, KR HA, QN JACOBOWITZ, DM TI CALRETININ IS EXPRESSED IN THE LEYDIG-CELLS OF RAT TESTIS SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE CALRETININ; IMMUNOCYTOCHEMISTRY; RNASE PROTECTION ASSAY; WESTERN BLOT; IN SITU HYBRIDIZATION; (RAT TESTIS); (LEYDIG CELL) ID CALCIUM-BINDING PROTEIN; IMMUNOHISTOCHEMICAL LOCALIZATION; GUINEA-PIG; BRAIN; NEURONS; IMMUNOREACTIVITY; STEROIDOGENESIS; IDENTIFICATION; CALMODULIN; SEQUENCE AB Calretinin, a highly evolutionarily conserved E-F hand calcium binding protein, is expressed predominantly in neurons, with a few exceptions. The function of calretinin is not known. We demonstrate the expression of calretinin mRNA and protein in rat testes. Immunocytochemistry and in situ hybridization reveal that calretinin expression in testis is localized to the interstitial Leydig cells. Western blot and ribonuclease protection analyses show that calretinin protein and mRNA in testis is the same as that expressed in brain. It is suggested that calretinin may play a role in the production of testosterone. RP STRAUSS, KI (reprint author), NIMH,CLIN SCI LAB,BLDG 10,RM 3D-48,BETHESDA,MD 20892, USA. NR 22 TC 40 Z9 41 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD OCT 18 PY 1994 VL 1219 IS 2 BP 435 EP 440 DI 10.1016/0167-4781(94)90069-8 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PN104 UT WOS:A1994PN10400024 PM 7918640 ER PT J AU HADLEY, EC AF HADLEY, EC TI THE NATIONAL-INSTITUTE-ON-AGINGS SUPPORT FOR DEVELOPMENT OF ACADEMIC GERIATRICS SO AMERICAN JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT Geriatrics Curriculum Development Conference and Initiative CY SEP 17-19, 1993 CL LEESBURG, VA RP HADLEY, EC (reprint author), NIA,GERIATR PROGRAM,GATEWAY BLDG,SUITE 3E327,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT 17 PY 1994 VL 97 SU 4A BP 34 EP 35 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA PM323 UT WOS:A1994PM32300016 ER PT J AU CUMMINGS, S HINDS, D YOUNG, WS AF CUMMINGS, S HINDS, D YOUNG, WS TI CORTICOTROPIN-RELEASING FACTOR MESSENGER-RNA INCREASES IN THE INFERIOR OLIVARY COMPLEX DURING HARMALINE-INDUCED TREMOR SO BRAIN RESEARCH LA English DT Article DE CORTICOTROPIN-RELEASING FACTOR; HARMALINE; INFERIOR OLIVE; IN SITU HYBRIDIZATION HISTOCHEMISTRY ID FACTOR MESSENGER-RNA; INSITU HYBRIDIZATION HISTOCHEMISTRY; CENTRAL NERVOUS-SYSTEM; PRECEREBELLAR NUCLEI; IONIC CONDUCTANCES; BETA-CARBOLINES; NEURONS INVITRO; RAT; CEREBELLAR; ADRENALECTOMY AB This study reports that corticotropin-releasing factor (CRF) expression within the inferior olivary complex (IOC) of the cat is increased 8 h after administration of the tremor-inducing beta-carboline harmaline. Following harmaline treatment, hybridization of an oligodeoxynucleotide complementary to CRF mRNA increased significantly in the dorsal accessory olive, subnuclei A and C of the medial accessory olive and the dorsal cap of Kooy, a subnucleus thought previously to be unresponsive physiologically to harmaline. At this early time point, greater increases in CRF mRNA hybridization were present in the caudal than the rostral IOC. These results support published reports that harmaline-mediated effects are more profound within the caudal than the rostral IOC, but also suggest that harmaline mediates cellular responses in inferior olivary neurons which are not related to activation of rhythmic firing. C1 NIMH, CELL BIOL LAB, BETHESDA, MD 20892 USA. RP UNIV CALIF DAVIS, DEPT ANAT PHYSIOL & CELL BIOL, 1321 HARING HALL, DAVIS, CA 95616 USA. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 FU NCRR NIH HHS [RR-05457] NR 66 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD OCT 17 PY 1994 VL 660 IS 2 BP 199 EP 208 DI 10.1016/0006-8993(94)91290-4 PG 10 WC Neurosciences SC Neurosciences & Neurology GA PK661 UT WOS:A1994PK66100003 PM 7820688 ER PT J AU HORII, Y BEELER, JF SAKAGUCHI, K TACHIBANA, M MIKI, T AF HORII, Y BEELER, JF SAKAGUCHI, K TACHIBANA, M MIKI, T TI A NOVEL ONCOGENE, OST, ENCODES A GUANINE-NUCLEOTIDE EXCHANGE FACTOR THAT POTENTIALLY LINKS RHO AND RAC SIGNALING PATHWAYS SO EMBO JOURNAL LA English DT Article DE ASSOCIATION; EFFECTOR; GUANINE NUCLEOTIDE EXCHANGE FACTOR; ONCOGENE; SMALL GTP-BINDING PROTEIN ID GTP-BINDING-PROTEIN; EXPRESSION CDNA CLONING; SACCHAROMYCES-CEREVISIAE; TRANSFORMING ACTIVITY; MOLECULAR-CLONING; ADP-RIBOSYLATION; DBL; GENE; PRODUCT; DOMAIN AB Transfection of NIH3T3 cells with an osteosarcoma expression cDNA library led to the appearance of foci of morphologically transformed cells which were found to harbor a novel oncogene, ost. The ost product was activated by truncation of the N-terminal domain of the ost proto-oncogene and was highly tumorigenic in nude mouse assays. The proto-ost cDNA, isolated subsequently, encodes a predicted protein of 100 kDa containing DH (Dbl homology) and PH (pleckstrin homology) domains. Ost is mainly phosphorylated on serine and localized in the cytoplasm. Purified Ost protein catalyzed guanine nucleotide exchange on RhoA and Cdc42 among the Rho and Ras family members tested, indicating that Ost can activate these small GTP-binding proteins. Ost did not detectably associate with RhoA or Cdc42, but interacted specifically with the GTP-bound form of Rac1, suggesting that Ost can function as an effector of Rac1. These results suggest that Ost is a critical regulatory component which links pathways that signal through Rac1, RhoA and Cdc42. Of the tissues examined, expression of osf was the highest in brain and could be localized to neurons and alpha-tanycytes, suggesting that Ost may participate in axonal transport in these specialized cells. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NIDR,BONE RES BRANCH,BETHESDA,MD 20892. NIDOCD,MOLEC GENET LAB,BETHESDA,MD 20892. NR 51 TC 191 Z9 192 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD OCT 17 PY 1994 VL 13 IS 20 BP 4776 EP 4786 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PN994 UT WOS:A1994PN99400007 PM 7957046 ER PT J AU BORNER, MM SCHNEIDER, E PIRNIA, F SARTOR, O TREPEL, JB MYERS, CE AF BORNER, MM SCHNEIDER, E PIRNIA, F SARTOR, O TREPEL, JB MYERS, CE TI THE DETERGENT TRITON X-100 INDUCES A DEATH PATTERN IN HUMAN CARCINOMA CELL-LINES THAT RESEMBLES CYTOTOXIC LYMPHOCYTE-INDUCED APOPTOSIS SO FEBS LETTERS LA English DT Article DE APOPTOSIS; HUMAN CANCER CELL LINE; TRITON X-100; CYTOTOXIC LYMPHOCYTE ID DNA FRAGMENTATION; DEGRADATION; LYSIS AB The detergent Triton X-100 (TX100) was used with the intention to establish a model for necrotic cell death. However, TX100 was found to induce apoptotic and necrotic death in prostate and colon cancer cell lines. Apoptosis was characterized by the typical morphologicaI features and internucleosomal DNA fragmentation. The rapid onset within 60 min and the lack of inhibition by cycloheximide indicated that apoptosis induced by TX100 was not dependent on protein synthesis. Removal of extracellular calcium blocked internucleosomal DNA fragmentation. This pattern of cell death shows a striking similarity to the effect of cytotoxic lymphocytes on their target cells. C1 NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. RI Borner, Markus/B-7583-2011 NR 23 TC 24 Z9 25 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD OCT 17 PY 1994 VL 353 IS 2 BP 129 EP 132 DI 10.1016/0014-5793(94)01023-4 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA PM917 UT WOS:A1994PM91700003 PM 7926036 ER PT J AU STAMPER, H AF STAMPER, H TI NIH TRIAGE SO SCIENTIST LA English DT Letter RP STAMPER, H (reprint author), NIMH,DIV EXTRAMURAL ACT,PARKLAWN BLDG,ROOM 9-105,ROCKVILLE,MD 20857, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 SN 0890-3670 J9 SCIENTIST JI Scientist PD OCT 17 PY 1994 VL 8 IS 20 BP 13 EP 13 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA PL332 UT WOS:A1994PL33200009 ER PT J AU SPIRITO, P PELLICCIA, A PROSCHAN, MA GRANATA, M SPATARO, A BELLONE, P CASELLI, G BIFFI, A VECCHIO, C MARON, BJ AF SPIRITO, P PELLICCIA, A PROSCHAN, MA GRANATA, M SPATARO, A BELLONE, P CASELLI, G BIFFI, A VECCHIO, C MARON, BJ TI MORPHOLOGY OF THE ATHLETES HEART ASSESSED BY ECHOCARDIOGRAPHY IN 947 ELITE ATHLETES REPRESENTING 27 SPORTS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR DIMENSIONS; CARDIOVASCULAR-DISEASE; NONINVASIVE EVALUATION; CARDIAC-HYPERTROPHY; DIASTOLIC FUNCTION; DISTANCE RUNNERS; DYNAMIC EXERCISE; WEIGHT LIFTERS; POPULATION; VOLUME AB In the present study, we used echocardiography to investigate the morphologic adaptations of the heart to athletic training in 947 elite athletes representing 27 sports who achieved national or international levels of competition. Cardiac morphology was compared for these sports, using multivariate statistical models. Left ventricular (LV) diastolic cavity dimension above normal (> 54 mm, ranging up to 66 mm) was identified in 362 (38%) of the 947 athletes. LV wall thickness above normal (> 12 mm, ranging up to 16 mm) was identified in only 16 (1.7%) of the athletes. Athletes training in the sports examined showed considerable differences with regard to cardiac dimensions. Endurance cyclists, rowers, and swimmers had the largest LV diastolic cavity dimensions and wall thickness. Athletes training in sports such as track sprinting, field weight events, and diving were at the lower end of the spectrum of cardiac adaptations to athletic training. Athletes training in sports associated with larger LV diastolic cavity dimensions also had higher values for wall thickness. Athletes training in isometric sports, such as weightlifting and wrestling, had high values for wall thickness relative to cavity dimension, but their absolute wall thickness remained within normal limits. Analysis of gender-related differences in cardiac dimensions showed that female athletes had smaller LV diastolic cavity dimension (average 2 mm) and smaller wall thickness (average 0.9 mm) than males of the same age and body size who were training in the same sport. Our results demonstrate that sports differ greatly with regard to their impact on LV dimensions and that, in general, athletes training in sports associated with large diastolic cavity dimension also have relatively high values for wall thickness. Our findings also show that gender has an influence on the morphology of the ''athlete's heart'' independent of type of sport, age, and body size. C1 IST SCI SPORT,REPARTO MED,ROME,ITALY. NIH,BIOSTAT RES BRANCH,BETHESDA,MD. MINNEAPOLIS HEART INST FDN,DIV CARDIOVASC RES,MINNEAPOLIS,MN. RP SPIRITO, P (reprint author), ENTE OSPEDALIERO OSPED GALLIERA,DIV CARDIOL,VIA VOLTA 8,I-16128 GENOA,ITALY. NR 30 TC 226 Z9 227 U1 1 U2 16 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 OCT 15 PY 1994 VL 74 IS 8 BP 802 EP 806 DI 10.1016/0002-9149(94)90439-1 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PK388 UT WOS:A1994PK38800014 PM 7942554 ER PT J AU FABSITZ, RR SHOLINSKY, P CARMELLI, D AF FABSITZ, RR SHOLINSKY, P CARMELLI, D TI GENETIC INFLUENCES ON ADULT WEIGHT-GAIN AND MAXIMUM BODY-MASS INDEX IN MALE TWINS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE ADULTS; BODY MASS INDEX; BODY WEIGHT; GENETICS; LONGITUDINAL STUDIES; MEN; TWINS; WEIGHT GAIN ID DISEASE RISK-FACTORS; CARDIOVASCULAR-DISEASE; IDENTICAL-TWINS; ENVIRONMENTAL-INFLUENCES; HEART-DISEASE; UNITED-STATES; HUMAN OBESITY; REARED APART; NHLBI TWIN; HERITABILITY AB The National Heart, Lung, and Blood Institute Twin Study is a multicenter, longitudinal study of 514 white, male twin pairs examined during military induction at the mean age of 20 years (1943) and by the National Heart, Lung, and Blood Institute Twin Study at mean ages 48 (1971), 58 (1981), and 63 years (1986). Of these, 121 of 254 monozygotic pairs and 113 of 260 dizygotic pairs had complete data for all examinations. Using these data, genetic influences on maximum body mass index (BMI) and changes in BMI during this 43-year interval were estimated. BMI (kg/m(2)) was calculated for each examination and for the maximum weight as recalled by the participant at the last examination. Regression equations were fitted to each person's four-examination measurements to estimate the trend in weight change over adulthood. Twins gained an average of 0.11 kg/m(2) per year from mean ages 20-63 years. Maximum BMI averaged 28.4 kg/m(2) for monzygotic twins acid 28.3 kg/m(2) for dizygotic twins. The distribution of the ages at maximum BMI appeared to be bimodal for each zygosity, with modes around ages 20 and 60 years. Heritability (variation attributable to genetic factors) was estimated to be 0.71 (95% confidence interval 0.55-0.87) for maximum BMI and 0.70 (95% confidence interval 0.55-0.84) for trend in adult weight gain. In contrast, variability of BMI around the trend line showed no evidence of significant genetic determination. C1 NHLBI,CLIN & GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. SRI INT,MENLO PK,CA 94025. NR 32 TC 67 Z9 67 U1 0 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 15 PY 1994 VL 140 IS 8 BP 711 EP 720 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PM453 UT WOS:A1994PM45300005 PM 7942773 ER PT J AU READ, JS CLEMENS, JD KLEBANOFF, MA AF READ, JS CLEMENS, JD KLEBANOFF, MA TI MODERATE LOW-BIRTH-WEIGHT AND INFECTIOUS-DISEASE MORTALITY DURING INFANCY AND CHILDHOOD SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE COMMUNICABLE DISEASES; INFANT, LOW BIRTH WEIGHT; INFANT MORTALITY ID GROWTH-RETARDATION AB The purpose of this study was to determine whether moderately low birth weight, singleton babies without congenital anomalies are at increased risk for postperinatal infectious disease mortality. The study cohort consisted of 54,795 live births assembled at 12 medical school-affiliated hospitals in different regions of the United States between 1959 and 1966 and followed prospectively. After exclusions of multiple gestation births, very low birth weight (less than 1,500 g) births, births with major congenital anomalies, and first-week deaths, 51,931 children remained for analysis. Postperinatal infectious disease mortality was assessed through age 7 years. Causes of death were classified independently by two pediatricians, blinded to birth weight status, according to an algorithm developed for the study. Moderately low birth weight infants and children were at increased risk of infectious disease mortality (relative risk (RR) = 2.49, 95% confidence interval (Cl) 1.74-3.55). The risk persisted among those whose deaths met our strictest criteria for infectious etiology and was sustained beyond infancy throughout the age interval under analysis. Among those with moderate low birth weight, there was an increased risk among those with preterm birth (RR = 2.77, 95% CI 1.19-6.46) but not among those who were born small-for-gestational age (RR = 1.19, 95% CI 0.37-3.83). The data suggest that moderate low birth weight renders individuals vulnerable to infectious disease mortality during both infancy and childhood. Among moderately low birth weight infants and children, this vulnerability appeared to be attributable primarily to preterm birth rather than to intrauterine growth retardation. RP READ, JS (reprint author), NICHHD,DESPR,6100 EXECUT BLVD,ROOM 7B03,BETHESDA,MD 20892, USA. NR 26 TC 28 Z9 28 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 OCT 15 PY 1994 VL 140 IS 8 BP 721 EP 733 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PM453 UT WOS:A1994PM45300006 PM 7942774 ER PT J AU STRATAKIS, CA CHROUSOS, GP AF STRATAKIS, CA CHROUSOS, GP TI CAPILLARITIS (PURPURA SIMPLEX) ASSOCIATED WITH USE OF AMINOGLUTETHIMIDE IN CUSHINGS-SYNDROME SO AMERICAN JOURNAL OF HOSPITAL PHARMACY LA English DT Article ID BREAST-CANCER AB Straightforward reports of unusual drug experiences are included in this section. While selected references may be cited, the purpose of a Drug Experience report is not to present an extensive review of the literature. A related section, Grand Rounds, includes papers that are well-documented patient case reports with a thorough review of the important literature to help put the case in perspective. Authors should report serious adverse drug reactions to the FDA medical products reporting program (MedWatch). A MedWatch form appears in the January 1 and July 1 issues of AJHP. Such reporting will not jeopardize the chances that AJHP will publish manuscripts on the same drug reactions. C1 NICHHD,PEDIAT ENDOCRINOL SECT,DEV ENDOCRINOL BRANCH,BETHESDA,MD. NICHHD,PEDIAT ENDOCRINOL TRAINING PROGRAM,BETHESDA,MD. GEORGETOWN UNIV,WASHINGTON,DC. RP STRATAKIS, CA (reprint author), NICHHD,PEDIAT ENDOCRINOL SECT,GEORGETOWN UNIV FELLOWSHIP PROGRAM,9000 ROCKVILLE PIKE,BLDG 10,BETHESDA,MD 20892, USA. NR 10 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 0002-9289 J9 AM J HOSP PHARM JI Am. J. Hosp. Pharm. PD OCT 15 PY 1994 VL 51 IS 20 BP 2589 EP 2591 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PN192 UT WOS:A1994PN19200006 PM 7847422 ER PT J AU BELSHE, RB CLEMENTS, ML KEEFER, MC GRAHAM, BS COREY, L SPOSTO, R WESCOTT, S LAWRENCE, D GORSE, GJ KENNEDY, D FREY, S LAMBERT, J SCHWARTZ, D DOLIN, R ROBERTS, N MCELRATH, J COOMBS, J WRIGHT, P KARZON, D FAST, P WALKER, MC MESTECKY, J JACKSON, S STABLEIN, D WOLFF, M AF BELSHE, RB CLEMENTS, ML KEEFER, MC GRAHAM, BS COREY, L SPOSTO, R WESCOTT, S LAWRENCE, D GORSE, GJ KENNEDY, D FREY, S LAMBERT, J SCHWARTZ, D DOLIN, R ROBERTS, N MCELRATH, J COOMBS, J WRIGHT, P KARZON, D FAST, P WALKER, MC MESTECKY, J JACKSON, S STABLEIN, D WOLFF, M TI INTERPRETING HIV SERODIAGNOSTIC TEST-RESULTS IN THE 1990S - SOCIAL RISKS OF HIV VACCINE STUDIES IN UNINFECTED VOLUNTEERS SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE HUMAN IMMUNODEFICIENCY VIRUS; SERODIAGNOSIS; AIDS VACCINES; HIV SEROPOSITIVITY; PREJUDICE ID GP160 RECOMBINANT VACCINIA; WESTERN-BLOT TESTS; NAIVE ADULTS; VIRUS; INFECTION; IMMUNOGENICITY; ANTIBODY; SAFETY AB Objective: To evaluate the influence of a human immunodeficiency virus (HIV) vaccine given to uninfected volunteers on the interpretation of serodiagnostic HIV test results. Design: Retrospective cohort study. Setting: 5 AIDS Vaccine Evaluation Units funded by the National Institute of Allergy and Infectious Diseases. Participants: The first 266 healthy adult volunteers (aged 18 to 60 years) who did not have HIV infection and whose history suggested that they were at low risk for acquiring HIV infection. Measurements: HIV antibody was measured by enzyme-linked immunosorbent assay (ELISA) and Western blot test, the results of which were interpreted on the basis of four different published criteria. Results: At some time during the first 12 months of the vaccine studies, 68% of volunteers were positive for HIV antibodies by ELISA. Depending on criteria used to interpret Western blot test results, 0% to 44% of volunteers had positive results that might have caused them to be incorrectly labeled as HIV infected. Conclusions: Significant social risks to volunteers participating in HIV vaccine studies were identified. Persons interpreting HIV serodiagnostic test results must consider that an HIV vaccine can cause a positive result in persons who are not infected. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT INT HLTH,BALTIMORE,MD 21205. UNIV ROCHESTER,SCH MED & DENT,DEPT MED,ROCHESTER,NY 14642. VANDERBILT UNIV,SCH MED,MED CTR N,DEPT MED,NASHVILLE,TN 37232. UNIV WASHINGTON,SCH MED,PACIFIC MED CTR AVEU,DEPT LAB MED,SEATTLE,WA 98144. EMMES CORP,POTOMAC,MD 20854. NIAID,DIV AIDS,BETHESDA,MD 20892. UNIV ALABAMA,BIRMINGHAM,AL. RP BELSHE, RB (reprint author), ST LOUIS UNIV,SCH MED,DIV INFECT DIS,3635 VISTA AVE,FDT-8N,ST LOUIS,MO 63110, USA. FU NIAID NIH HHS [N01-AI-05064, N01-AI-05061, N01-AI-05063] NR 13 TC 30 Z9 31 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 15 PY 1994 VL 121 IS 8 BP 584 EP & PG 0 WC Medicine, General & Internal SC General & Internal Medicine GA PL486 UT WOS:A1994PL48600005 PM 8085690 ER PT J AU DEMAZANCOURT, P GOLDSMITH, PK WEINSTEIN, LS AF DEMAZANCOURT, P GOLDSMITH, PK WEINSTEIN, LS TI INHIBITION OF ADENYLATE-CYCLASE ACTIVITY BY GALANIN IN RAT INSULINOMA CELLS IS MEDIATED BY THE G-PROTEIN G(I3) SO BIOCHEMICAL JOURNAL LA English DT Article ID GTP-BINDING-PROTEIN; ALPHA-SUBUNIT; SIGNAL TRANSDUCTION; REGULATORY PROTEIN; SECRETING CELLS; GAMMA-SUBUNITS; BETA-SUBUNITS; K+ CHANNELS; CYCLIC-AMP; RECEPTOR AB Galanin inhibits adenylate cyclase activity and insulin secretion and modulates ion channels in pancreatic beta-cells through pertussis-toxin-sensitive G-protein(s). Antibodies directed against the C-terminal region of specific G-protein alpha-subunits were used to determine which G-protein(s) couple galanin receptors to inhibition of adenylate cyclase in the rat insulinoma cell line RINm5F. Preincubation of membranes with EC antibody (anti-alpha(i3)) decreased the inhibition of forskolin-stimulated adenylate cyclase activity by galanin (100 nM) by 45% compared with control IgG (P < 0.05) whereas preincubation with AS (anti-alpha(i1), alpha(i2)) or GO (anti-alpha(o)) antibodies had no significant effect. To confirm these results, RINm5F cells were exposed intermittently over a 4-day period to phosphorothioate oligodeoxynucleotides that were either sense or antisense to alpha(i1), alpha(i2), alpha(i3) or alpha(o). Oligodeoxynucleotides antisense to alpha i2, alpha i3 and alpha(o) specifically decreased the levels of the targeted alpha-subunit in membranes. alpha(i1) was undetectable in these cells. Inhibition of adenylate cyclase activity by galanin was largely abolished in membranes from cells exposed to the oligodeoxynucleotide antisense to alpha(i3), whereas all other oligodeoxynucleotides had no significant effect on this pathway. Indirect immunofluorescence and immunoblotting of specific membrane fractions with EC antibody show significant localization of alpha(i3) to intracellular membrane compartments. These results suggest that G(i3) is the G protein that couples galanin receptors to inhibition of adenylate cyclase activity in RINm5F cells. C1 NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. RI Weinstein, Lee/I-5575-2015; OI Weinstein, Lee/0000-0002-1899-5152 NR 56 TC 24 Z9 24 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 OCT 15 PY 1994 VL 303 BP 369 EP 375 PN 2 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PN102 UT WOS:A1994PN10200007 PM 7526840 ER PT J AU LI, CCH KORNER, M FERRIS, DK CHEN, EY DAI, RM LONGO, DL AF LI, CCH KORNER, M FERRIS, DK CHEN, EY DAI, RM LONGO, DL TI NF-KAPPA-B/REL FAMILY MEMBERS ARE PHYSICALLY ASSOCIATED PHOSPHOPROTEINS SO BIOCHEMICAL JOURNAL LA English DT Article ID B TRANSCRIPTION FACTOR; TRANSFORMED LYMPHOID-CELLS; REL ONCOGENE PRODUCT; C-REL; PROTOONCOGENE PRODUCT; DNA-BINDING; V-REL; RETICULOENDOTHELIOSIS VIRUS; CELLULAR PROTEINS; INHIBITOR AB We performed radioimmunoprecipitation followed by serial immunoblots to show that, in the unstimulated Jurkat T cell line, the NF-kappa B/Rel family proteins, p80-c-Rel, p105-NF-kappa B, p65-NF-kappa B, p50-NF-kappa B and p36-I kappa B alpha, can be detected as complexes using antisera against c-Rel, p105-NF-kappa B or p65-NF-kappa B. p36-I kappa B alpha and p105, both known inhibitors of NF-kappa B function, can physically associate with NF-kappa B/Rel family members, but not with each other. In vivo and in vitro phosphorylation experiments demonstrated that NF-kappa B/Rel family members, including p105, c-Rel, p50, p65 (for the first time for p50 and p65) and p36-I kappa B alpha are also phosphoproteins: Phosphoserine and phosphothreonine residues were identified in these proteins isolated from unstimulated Jurkat cells. Both unphosphorylated and hyperphosphorylated forms of p36-I kappa B alpha were found in the complexes, suggesting that hyperphosphorylated I kappa B alpha is still capable of associating with the NF-kappa B/Rel family members. After stimulation with phorbol 12-myristate 13-acetate and phytohaemagglutinin for 10 min, p105-NF-kappa B and p50-NF-kappa B, but not p36-I kappa B, were highly phosphorylated. Phosphopeptide mapping of p105 showed that phorbol ester/phytohaemagglutinin stimulation may change p105 phosphorylation qualitatively. C1 HOP LA PITIE SALPETRIERE,IMMUNOL CELLULAIRE & TISSULAIRE LAB,CNRS,URA 625,F-75013 PARIS,FRANCE. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. RP LI, CCH (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702, USA. NR 37 TC 43 Z9 43 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 OCT 15 PY 1994 VL 303 BP 499 EP 506 PN 2 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PN102 UT WOS:A1994PN10200025 PM 7980409 ER PT J AU ROTTEM, M OKADA, T GOFF, JP METCALFE, DD AF ROTTEM, M OKADA, T GOFF, JP METCALFE, DD TI MAST-CELLS CULTURED FROM THE PERIPHERAL-BLOOD OF NORMAL DONORS AND PATIENTS WITH MASTOCYTOSIS ORIGINATE FROM A CD34+ FC(EPSILON)RI(-) CELL-POPULATION SO BLOOD LA English DT Article ID UMBILICAL-CORD BLOOD; C-KIT LIGAND; BONE-MARROW; RECOMBINANT HUMAN; PROGENITOR CELLS; HISTAMINE; DIFFERENTIATION; APPEARANCE; LEUKEMIA; INVITRO AB Mast cells may be cultured from human peripheral blood in the presence of recombinant human stem cell factor (rhSCF). The characteristics of the cells in peripheral blood that give rise to mast cells are unknown. Because mast cell precursors in human marrow are CD34(+), human peripheral blood mononuclear cells from patients with mastocytosis and normal controls were sorted on the basis of CD34 expression and the positive and negative cell populations were cultured in rhSCF, recombinant human interleukin-3 (rhIL-3), or both for 6 weeks. Cell cultures were examined every 2 weeks for total and mast cell number and cell differential using Wright Giemsa and acid toluidine blue stains and antibodies to mast cell tryptase and chymase, cell-associated histamine, and expression of CD34, c-kit, Fc(epsilon)RI, and Fc(gamma)RII using flow cytometric analysis. The ultrastructural anatomy of mast cells was examined by electron microscopy. Peripheral blood CD34(+) cells cultured in rhSCF with or without rhIL-3 gave rise to cell cultures consisting of greater than 80% mast cells by 6 weeks. CD34(+) cells cultured in rhIL-3 alone did not give rise to mast cells, whereas rhIL-3 plus rhSCF increased the final mast cell number eightfold when compared with cells cultured in rhSCF alone. Mast cells increased concomitantly with a decrease in large undifferentiated mononuclear cells. CD34(-) cells did not give rise to mast cells. Histamine content per cell at 6 weeks was approximately 5 pg. Electron microscopy of 4-week cultures showed immature mast cells containing predominantly tryptase-positive granules that were either homogeneous or contained lattice structures, partial scroll patterns, or central dense cores and mixtures of vesicles, fine granular material, and particles. The CD34(+) population at day 0 expressed Kit (65%) and Fc(gamma)RII (95%), but not Fc(epsilon)RI, by fluorescence-activated cell sorter analysis. At 6 weeks, CD34(+)-derived mast cells exhibited Fc(epsilon)RI in addition to Kit and Fc(gamma)RII, and were negative for CD34 antigen. Patients with mastocytosis showed a higher number of mast cells per CD34(+) cell cultured compared with normal controls. Thus, the mast cell precursor in human peripheral blood is CD34(+)/Fc(epsilon)RI(-) and gives rise to mast cells in the presence of rhSCF with or without rhIL-3, and the number of mast cells arising per CD34(+) cell in culture is greater when the CD34(+) cells are obtained from patients with mastocytosis compared with normal subjects. This is a US government work. There are no restrictions on its use. C1 NIAID,CLIN INVEST LAB,ALLERG DIS SECT,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DIV MOLEC VIROL & IMMUNOL,ROCKVILLE,MD. NR 24 TC 159 Z9 161 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 OCT 15 PY 1994 VL 84 IS 8 BP 2489 EP 2496 PG 8 WC Hematology SC Hematology GA PL359 UT WOS:A1994PL35900012 PM 7522630 ER PT J AU COCKAYNE, DA BODINE, DM CLINE, A NIENHUIS, AW DUNBAR, CE AF COCKAYNE, DA BODINE, DM CLINE, A NIENHUIS, AW DUNBAR, CE TI TRANSGENIC MICE EXPRESSING ANTISENSE INTERLEUKIN-3 RNA DEVELOP A B-CELL LYMPHOPROLIFERATIVE SYNDROME OR NEUROLOGIC DYSFUNCTION SO BLOOD LA English DT Article ID MOUSE BONE-MARROW; HUMAN RECOMBINANT IL-3; PRO-LYMPHOCYTE-T; MULTI-CSF IL-3; GROWTH-FACTOR; MONOCLONAL-ANTIBODIES; HEMATOPOIETIC-CELLS; STIMULATING FACTOR; PRECURSOR CELLS; GENE-EXPRESSION AB Transgenic mice that expressed antisense interleukin-3 (AS-IL-3) RNA were generated and exhibited either a B-cell lymphoproliferative syndrome or progressive neurologic dysfunction. Each syndrome occurred in the founder or progeny mice of three separate transgenic lines. The lymphoproliferative process involved the accumulation, within peripheral lymphoid organs, of B220(+)/slgM(-) pre-B cells that had immunoglobulin (Ig) genes predominantly in germline configuration and expressed lambda 5 and Rag-1 transcripts. Transgenic animals that developed neurologic dysfunction exhibited circling behavior that progressed to ataxia and terminal inanition. AS-IL-3 transcripts were detected in matore CD3(+) T cells of asymptomatic transgenic animals, as well as in B220(+)/slgM(-) pre-B cells, and CD3(+) T cells from animals with the lymphoproliferative syndrome. AS-IL-3 transcripts were also detected in the brains of both young asymptomatic transgenic animals and older transgenic animals with neurologic dysfunction. Decreased IL-3 production from ConA-stimulated splenocytes was observed in asymptomatic transgenic animals. These observations suggest that this cytokine may have important roles in B lymphopoiesis and neurologic function. (C) 1994 by The American Society of Hematology. C1 NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. RP COCKAYNE, DA (reprint author), DNAX RES INST MOLEC & CELLULAR BIOL INC,DEPT IMMUNOL,901 CALIF AVE,PALO ALTO,CA 94131, USA. NR 64 TC 32 Z9 32 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 OCT 15 PY 1994 VL 84 IS 8 BP 2699 EP 2710 PG 12 WC Hematology SC Hematology GA PL359 UT WOS:A1994PL35900035 PM 7919383 ER PT J AU BROWNING, PJ SECHLER, JMG KAPLAN, M WASHINGTON, RH GENDELMAN, R YARCHOAN, R ENSOLI, B GALLO, RC AF BROWNING, PJ SECHLER, JMG KAPLAN, M WASHINGTON, RH GENDELMAN, R YARCHOAN, R ENSOLI, B GALLO, RC TI IDENTIFICATION AND CULTURE OF KAPOSIS SARCOMA-LIKE SPINDLE CELLS FROM THE PERIPHERAL-BLOOD OF HUMAN IMMUNODEFICIENCY VIRUS-1-INFECTED INDIVIDUALS AND NORMAL CONTROLS SO BLOOD LA English DT Article ID HUMAN-ENDOTHELIAL CELLS; LONG-TERM CULTURE; MONOCLONAL-ANTIBODIES; DIFFERENTIATION ANTIGENS; INFLAMMATORY TISSUES; GENE-EXPRESSION; MYELOID CELLS; TAT PROTEIN; T-CELLS; B-CELLS AB We examined 26 patients with human immunodeficiency virus-1 (HIV-1)-associated Kaposi's sarcoma (KS), and 76 HIV-1-infected (HIV-1(+)) people without KS or uninfected (HIV-1(-)) controls for the presence of circulating KS-like spindle cells. Adherent cells that had spindle morphology and several characteristics of spindle cells of KS lesions (KS cells) were identified in the peripheral blood mononuclear cell fraction only after culture in the presence of conditioned medium (CM) from activated lymphocytes. The peripheral blood-derived spindle cells (PBsc) expressed a variety of endothelial cell markers, such as Ulex europaeus I lectin, EN4, EN2/3, EN7/44, CD13, CD34, CD36, CD54, ELAM-1, and HLA-DR. However, they were negative for CD2, CD19, PaIE, and factor VIII-related antigen. The PBsc produced angiogenic factors as evidenced by the ability of CM from these cells to promote growth of normal vascular endothelial cells. In addition, subcutaneously injected PBsc stimulated angiogenesis in vivo in athymic nude mice. We determined that the number of PBsc grown from the peripheral blood of HIV-1(+) patients with KS or at high risk to develop KS were increased by 78-fold (P = .0001) and 18-fold (P = .005), respectively, when compared with HIV-1(-) controls. The number of spindle cells cultured from the HIV-1(+) patients at low risk for developing KS, eg, HIV-1(+) injection drug users, showed no statistical increase when compared with HIV-1(-) controls. The presence of increased PBsc with characteristics of KS cells in HIV-1(+) KS patients or patients at high risk for developing KS gives insights into the origin of KS cells and may explain the multifocal nature of the disease. In addition, this may be useful in predicting the risk of KS development. (C) 1994 by The American Society of Hematology. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892. N SHORE UNIV HOSP,DEPT INTERNAL MED,DIV INFECT DIS & IMMUNOL,MANHASSET,NY. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 61 TC 89 Z9 90 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 OCT 15 PY 1994 VL 84 IS 8 BP 2711 EP 2720 PG 10 WC Hematology SC Hematology GA PL359 UT WOS:A1994PL35900036 PM 7522639 ER PT J AU BOSCH, F JARES, P CAMPO, E LOPEZGUILLERMO, A PIRIS, MA VILLAMOR, N TASSIES, D JAFFE, ES MONTSERRAT, E ROZMAN, C CARDESA, A AF BOSCH, F JARES, P CAMPO, E LOPEZGUILLERMO, A PIRIS, MA VILLAMOR, N TASSIES, D JAFFE, ES MONTSERRAT, E ROZMAN, C CARDESA, A TI PRAD-1 CYCLIN D1 GENE OVEREXPRESSION IN CHRONIC LYMPHOPROLIFERATIVE DISORDERS - A HIGHLY SPECIFIC MARKER OF MANTLE CELL LYMPHOMA SO BLOOD LA English DT Article ID T(11-14) CHROMOSOME-TRANSLOCATION; CHRONIC LYMPHOCYTIC-LEUKEMIA; BCL-1 GENE; T(11-14)(Q13-Q32) TRANSLOCATION; INTERMEDIATE DIFFERENTIATION; CENTROCYTIC LYMPHOMA; CANDIDATE ONCOGENE; REARRANGEMENT; BREAKPOINT; CLONING AB The t(11;14)(q13;q32) translocation and its molecular counterpart bcl-1 rearrangement are frequently associated with mantle cell lymphomas (MCLs) and only occasionally with other variants of B-cell lymphoid malignancies. This translocation seems to activate the expression of PRAD-1/cyclin D1 gene located downstream from the major breakpoint cluster region of this rearrangement. However, the possible overexpression of this gene in other lymphoproliferative disorders independently of bcl-1 rearrangement is unknown. We have examined the overexpression of PRAD-1 gene in a large series of 142 lymphoproliferative disorders including 20 MCLs by Northern blot analysis. Cytogenetic and/or bcl-1 rearrangement analysis with 2 probes (MTC, p94PS) were performed in 28 cases. Strong PRAD-1 overexpression was observed in 19 of the 20 MCLs including 3 gastrointestinal forms and 4 blastic variants. t(11;14) and/or bcl-1 rearrangement was detected in 6 of the 12 MCLs examined. No correlation was found between the different levels of mRNA expression and the pathologic characteristics of the lymphoma. Among chronic lymphoproliferative disorders other than MCL, only 1 atypical chronic lymphocytic leukemia (CLL) with a t(11;14) translocation and bcl-1 rearrangement and the 2 hairy cell leukemias (HCLs) analyzed showed upregulation of PRAD-1 gene. The expression in the 2 HCLs was lower than in MCL, and no bcl-1 rearrangement was observed. These findings indicate that PRAD-1 overexpression is a highly sensitive and specific molecular marker of MCL but it may also be upregulated in some B-CLLs and in HCL. (C) 1994 by The American Society of Hematology. C1 UNIV BARCELONA,HOSP CLIN BARCELONA,DEPT ANAT PATHOL,E-08036 BARCELONA,SPAIN. UNIV BARCELONA,HOSP CLIN BARCELONA,POSTGRAD SCH HEMATOL FARRERAS VALENTI,E-08036 BARCELONA,SPAIN. UNIV LLEIDA,DEPT BASIC MED SCI,LLEIDA,SPAIN. HOSP VIRGEN SALUD,DEPT ANAT PATHOL,TOLEDO,SPAIN. NCI,PATHOL LAB,HEMATOPATHOL SECT,BETHESDA,MD 20892. OI Bosch, Francesc/0000-0001-9241-2886; Piris, Miguel A/0000-0001-5839-3634; Campo, elias/0000-0001-9850-9793 NR 43 TC 283 Z9 285 U1 1 U2 12 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 OCT 15 PY 1994 VL 84 IS 8 BP 2726 EP 2732 PG 7 WC Hematology SC Hematology GA PL359 UT WOS:A1994PL35900038 PM 7919385 ER PT J AU COLE, DJ WEIL, DP SHAMAMIAN, P RIVOLTINI, L KAWAKAMI, Y TOPALIAN, S JENNINGS, C ELIYAHU, S ROSENBERG, SA NISHIMURA, MI AF COLE, DJ WEIL, DP SHAMAMIAN, P RIVOLTINI, L KAWAKAMI, Y TOPALIAN, S JENNINGS, C ELIYAHU, S ROSENBERG, SA NISHIMURA, MI TI IDENTIFICATION OF MART-1-SPECIFIC T-CELL RECEPTORS - T-CELLS UTILIZING DISTINCT T-CELL RECEPTOR VARIABLE AND JOINING REGIONS RECOGNIZE THE SAME TUMOR EPITOPE SO CANCER RESEARCH LA English DT Note ID CYTOLYTIC LYMPHOCYTES-T; INFILTRATING LYMPHOCYTES; AUTOLOGOUS MELANOMA; ANTIGEN; CLONES; CHAIN; IMMUNOTHERAPY; SPECIFICITY; NONAPEPTIDE; MOLECULE AB Tumor-specific cytotoxic T lymphocytes (CTLs) can mediate tumor regression in patients with metastatic melanoma and play a central role in the immune response to cancer. The recent identification of shared melanoma antigens has raised the possibility of a limited melanoma-specific T-cell receptor (TCR) repertoire, but subsequent studies have been controversial and difficult to interpret without knowing which tumor-associated antigens (TAAs) are being recognized by specific TCRs. However, the recent cloning of several melanoma TAAs now allows for the identification of the specifically recognized TAA and its epitope. We evaluated the TCR of two clonal CD8(+) CTL lines, A42 and 1E2, from two HLA-A2(+) patients with metastatic melanoma. Both CTL lines were MART-1 specific, and both demonstrate reactivity to the same epitope when presented in an HLA-A2.1 context. The TCR genes of the two clones were sequenced. All of the productively rearranged A42 TCR beta chain genes were V beta 7/D beta 2.1/J beta 2.7/C beta 2; the TCR alpha chain genes were V alpha 21/J alpha 42/C alpha. The 1E2 TCR beta chain genes were V beta 3/D beta 1.1/J beta 1.1/C beta 1, and TCR alpha chains were V alpha 25/J alpha 54/C alpha: This study is the first report of TCR sequences specific for a melanoma epitope. These TCR clones may be useful for the development of more effective immunotherapies and in studies of the mechanism of T cell recognition of tumor antigen. They also provide direct evidence that the immune system can provide more than one TCR capable of recognizing a TAA epitope. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. RI Kawakami, Yutaka /E-7429-2013; OI Kawakami, Yutaka /0000-0003-4836-2855; Rivoltini, Licia/0000-0002-2409-6225 NR 38 TC 58 Z9 58 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 OCT 15 PY 1994 VL 54 IS 20 BP 5265 EP 5268 PG 4 WC Oncology SC Oncology GA PL558 UT WOS:A1994PL55800005 PM 7522957 ER PT J AU MELNICK, RL SILLS, RC ROYCROFT, JH CHOU, BJ RAGAN, HA MILLER, RA AF MELNICK, RL SILLS, RC ROYCROFT, JH CHOU, BJ RAGAN, HA MILLER, RA TI ISOPRENE, AN ENDOGENOUS HYDROCARBON AND INDUSTRIAL-CHEMICAL, INDUCES MULTIPLE ORGAN NEOPLASIA IN RODENTS AFTER 26 WEEKS OF INHALATION EXPOSURE SO CANCER RESEARCH LA English DT Article ID HEPATIC-MICROSOMAL METABOLISM; NATIONAL TOXICOLOGY PROGRAM; B6C3F1 MICE; SPECIES-DIFFERENCES; 1,3-BUTADIENE; CARCINOGENICITY; BUTADIENE; RATS; PHARMACOKINETICS; MORTALITY AB Isoprene, the 2-methyl analogue of 1,3-butadiene, is a high production chemical used largely in the manufacture of synthetic rubber and is the major endogenous hydrocarbon exhaled in human breath. Thirteen-week inhalation toxicology studies of isoprene were conducted in male and female F344 rats and B6C3F(1) mice at exposure concentrations of 0, 70, 220, 700, 2200, and 7000 ppm (6 h/day; 5 days/week). In addition, 26-week inhalation studies at the same exposure levels, followed by a 26-week recovery period, were conducted in male rats and mice. The 13-week exposures produced no discernible exposure-related toxic effects in rats. Interstitial cell hyperplasia of the testis was observed in all male rats in the 7000 ppm group after 26 weeks of exposure; following the 26-week recovery period the only effect in rats was a marginal increase in benign testicular interstitial cell tumors. In mice, isoprene induced toxic and carcinogenic effects at multiple organ sites. Following the 26-week exposure and 26-week recovery periods, incidences of neoplastic lesions in the liver, lung, forestomach, and harderian gland were significantly increased. Neoplastic effects were observed at 700 ppm and higher exposures. Nonneoplastic lesions in mice exposed to isoprene included spinal cord degeneration, testicular atrophy, degeneration of the olfactory epithelium, and epithelial hyperplasia of the forestomach. A partial hindlimb paralysis and a nonresponsive macrocytic anemia were also seen in mice. Most of the toxic and carcinogenic effects caused by isoprene, as well as the species' difference in response, had been observed after inhalation exposures to 1,3-butadiene. C1 PACIFIC NW LAB, RICHLAND, WA 99352 USA. RP MELNICK, RL (reprint author), NIEHS, ENVIRONM CARCINOGENESIS PROGRAM, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 47 TC 44 Z9 44 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 1994 VL 54 IS 20 BP 5333 EP 5339 PG 7 WC Oncology SC Oncology GA PL558 UT WOS:A1994PL55800015 PM 7923161 ER PT J AU POTISCHMAN, N FALK, RT LAIMING, VA SIITERI, PK HOOVER, RN AF POTISCHMAN, N FALK, RT LAIMING, VA SIITERI, PK HOOVER, RN TI REPRODUCIBILITY OF LABORATORY ASSAYS FOR STEROID-HORMONES AND SEX HORMONE-BINDING GLOBULIN SO CANCER RESEARCH LA English DT Article ID POST-MENOPAUSAL WOMEN; BREAST-CANCER RISK; ENDOMETRIAL CANCER; POSTMENOPAUSAL WOMEN; JAPANESE WOMEN; ESTRADIOL; SERUM; ESTROGENS; PERCENTAGE; OBESITY AB The relationship of serum hormones to cancer risk has recently been pursued in epidemiological studies, but few have reported on the reproducibility of laboratory findings. Prior to conducting a study of endogenous hormones and endometrial cancer, we evaluated the reproducibility of measurements for several hormones (estrone, estradiol, free estradiol, albumin-bound estradiol, and androstenedione) and sex hormone-binding globulin. We obtained a single unit of blood from each of six women and prepared aliquots of serum for repeated testing. Three laboratories analyzed multiple samples on consecutive working days from which estimates of intraassay and interassay measurement variability were obtained. For estrone and estradiol, a log transformation of the data produced distributions which were nearly normal and permitted the use of parametric statistical tests. In general, we found measurements for most hormones varied considerably between assays. Moreover, differences were observed in the absolute values of sex hormone-binding globulin and of the hormones, particularly for estrone and estradiol, from one laboratory to the next. Our findings suggest that variability of current laboratory procedures may hamper efforts to study the association between disease and endogenous hormones in epidemiological studies. In addition, validation of hormone assays is essential in order to assure standardized results and enable comparisons of data across studies. C1 MICROBIOL ASSOCIATES INC,ROCKVILLE,MD 20850. RP POTISCHMAN, N (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EXECUT PLAZA N,SUITE 443,BETHESDA,MD 20892, USA. NR 23 TC 46 Z9 46 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 1994 VL 54 IS 20 BP 5363 EP 5367 PG 5 WC Oncology SC Oncology GA PL558 UT WOS:A1994PL55800020 PM 7923166 ER PT J AU MARION, S BRAUN, JM ROPARS, A KOHN, LD CHARREIRE, J AF MARION, S BRAUN, JM ROPARS, A KOHN, LD CHARREIRE, J TI INDUCTION OF AUTOIMMUNITY BY IMMUNIZATION OF MICE WITH HUMAN THYROTROPIN RECEPTOR SO CELLULAR IMMUNOLOGY LA English DT Article ID BINDING INHIBITOR IMMUNOGLOBULINS; THYROID-STIMULATING ACTIVITY; GRAVES-DISEASE; GONADOTROPIN RECEPTORS; IMMUNE-MECHANISMS; MOLECULAR-CLONING; RABBIT ANTIBODIES; HORMONE-BINDING; TSH RECEPTOR; EXPRESSION AB The development of autoimmunity was investigated after repeated immunizations with human thyrotropin receptor (hTSH-R) of five congenic strains of female and male mice. After each immunization, free T3 levels and antibodies to hTSH-R and to six peptides of the hTSH-R were assayed. Our results showed that H-2s and H-2q female mice developed features of autoimmunity such as antibody responses to hTSH-R and to hTSH-R peptides, transient variations in the levels of free T3 thyroid hormone, and lymphocytic infiltrations in their thyroid glands. Concerning the antibody responses to hTSH-R peptides, we found that peptide P1 (352-366) contained a major B cell epitope. Furthermore, strain-specific B cell epitope was exemplified by peptide 92 (12-30) and two male- and female-specific B cell epitopes were located in peptides 91 (32-46) and 93 (316-330), respectively. These features appeared rather related to hyperthyroidism. (C) 1994 Academic Press, Inc. C1 NIDDK,BETHESDA,MD 20892. RP MARION, S (reprint author), HOP COCHIN,INSERM,U283,F-75674 PARIS 14,FRANCE. NR 36 TC 27 Z9 27 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD OCT 15 PY 1994 VL 158 IS 2 BP 329 EP 341 DI 10.1006/cimm.1994.1280 PG 13 WC Cell Biology; Immunology SC Cell Biology; Immunology GA PP138 UT WOS:A1994PP13800006 PM 7923386 ER PT J AU KHOCHBIN, S WOLFFE, AP AF KHOCHBIN, S WOLFFE, AP TI DEVELOPMENTALLY-REGULATED EXPRESSION OF LINKER-HISTONE VARIANTS IN VERTEBRATES SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Review ID MURINE ERYTHROLEUKEMIA-CELLS; BASAL LEVEL TRANSCRIPTION; EARLY XENOPUS-EMBRYOS; H1(0) MESSENGER-RNA; S-PHASE; PROMOTER REGION; H1T GENE; H-5 GENE; CYCLE REGULATION; BINDING-PROTEIN AB The identification of histone H1 variants in vertebrates suggests that these proteins may have specialized functions. During embryonic development, a correspondence between the expression of each of the linker-histone variants and the proliferative and transcriptional activity of embryonic cells can be observed. Analysis of the developmentally regulated expression of these variants leads to the subdivision of these variants into distinct classes. This subdivision may also provide insight into the significance of the differential expression of variants and the roles individual linker histones have in chromatin structure and function. C1 NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. RP KHOCHBIN, S (reprint author), CEN GRENOBLE,CEA,DBMS,INSERM,U309,MOLEC CYCLE CELLULAIRE LAB,17 RUE MARTYRS,F-38054 GRENOBLE 9,FRANCE. RI Khochbin, Saadi/M-8090-2013 NR 92 TC 87 Z9 87 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD OCT 15 PY 1994 VL 225 IS 2 BP 501 EP 510 DI 10.1111/j.1432-1033.1994.00501.x PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PN689 UT WOS:A1994PN68900001 PM 7957165 ER PT J AU GLICK, AB LEE, MM DARWICHE, N KULKARNI, AB KARLSSON, S YUSPA, SH AF GLICK, AB LEE, MM DARWICHE, N KULKARNI, AB KARLSSON, S YUSPA, SH TI TARGETED DELETION OF THE TGF-BETA-1 GENE CAUSES RAPID PROGRESSION TO SQUAMOUS-CELL CARCINOMA SO GENES & DEVELOPMENT LA English DT Article DE TGF-BETA-1 GENE; TARGETED DELETION; KERATINOCYTES; FIBROBLASTS; SQUAMOUS CELL CARCINOMA; TUMOR CELL PROLIFERATION ID TRANSFORMING GROWTH FACTOR-BETA-1; MOUSE SKIN CARCINOGENESIS; V-HA-RAS; FACTOR-BETA; TGF-BETA; MALIGNANT CONVERSION; TUMOR PROGRESSION; MESSENGER-RNA; IMMUNOHISTOCHEMICAL LOCALIZATION; CHEMICAL CARCINOGENESIS AB To study the contribution of autocrine and paracrine TGE-beta 1 to tumor progression in a well-defined system of multistage carcinogenesis, keratinocytes with a targeted deletion of the TGF-beta 1 gene were initiated in vitro with the v-ras(Ha) oncogene and their in vivo tumorigenic properties were determined by skin grafting initiated cells onto athymic mice in combination with either wild-type or null dermal fibroblasts. Grafts of v-ras(Ha)-initiated null keratinocytes progressed rapidly to multifocal squamous cell carcinomas within dysplastic papillomas irrespective of the fibroblast genotype, whereas the initiated control genotypes formed well-differentiated papillomas. Malignant progression was not associated with mutations in the c-ras(Ha) gene, alterations in p53 protein, or loss of responsiveness to TGF-beta 1. The tumor cell labeling index was elevated in grafts of initiated null keratinocytes with wild-type fibroblasts compared to tumors of other genotypes. However, labeling index in all tumors was reduced when TGF-beta 1 null fibroblasts formed the stroma. The null tumor cells could not accumulate TGE-beta 1 from the host, but grafts of uninitiated null keratinocytes, which formed a normal epidermis, became TGE-beta 1 positive even though they did not express TGF-beta 1 mRNA. These results demonstrate that autocrine TGF-beta 1 suppresses the frequency and rate of malignant progression, and that autocrine and paracrine TGF-beta 1 can have opposing effects on tumor cell proliferation. The lack of paracrine inhibition of tumor tell progression appears to result from the inability of tumor cells to localize host-derived TGF-beta 1 by a mechanism that operates in normal cells. C1 NINCDS,DEV & METAB NEUROL BRANCH,MOLEC MED GENET SECT,BETHESDA,MD 20892. RP GLICK, AB (reprint author), NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD, USA. OI Darwiche, Nadine/0000-0002-1862-5426 NR 77 TC 130 Z9 134 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD OCT 15 PY 1994 VL 8 IS 20 BP 2429 EP 2440 DI 10.1101/gad.8.20.2429 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA PN451 UT WOS:A1994PN45100004 PM 7958907 ER PT J AU ZABRENETZKY, V HARRIS, CC STEEG, PS ROBERTS, DD AF ZABRENETZKY, V HARRIS, CC STEEG, PS ROBERTS, DD TI EXPRESSION OF THE EXTRACELLULAR-MATRIX MOLECULE THROMBOSPONDIN INVERSELY CORRELATES WITH MALIGNANT PROGRESSION IN MELANOMA, LUNG AND BREAST-CARCINOMA CELL-LINES SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID TUMOR; METASTASIS; ADHESION; PROTEINS; BIOLOGY; DISEASE; BINDING; CANCER AB Thrombospondin (TSP) is a member of a family of extracellular matrix glycoproteins that may participate in multiple aspects of the metastatic cascade. We report an inverse correlation of steady-state Thbs-1 mRNA and protein expression with malignant progression among murine melanoma and human lung and breast carcinoma cell lines. Murine K-1735 melanoma cell lines of low metastatic potential, including K-1735 lines transfected with the murine nm23-1 cDNA, expressed higher TSP levels than related highly metastatic lines. In a model system of lung carcinoma malignant progression, immortalized human branchial epithelial cells expressed higher TSP levels than v-Ki-ras, v-Ha-ras or n-ras transfectants, which in turn expressed higher TSP levels than tumor-derived, more aggressive variants. Among 3 unrelated breast carcinoma cell lines, Thbs-1 steady-state mRNA levels were greater in the 2 nonmetastatic lines than the metastatic line. Our data show that malignant progression in some cell lines is associated with reduced TSP expression. The suppressive effects of nm23-1 transfection an metastatic potential are also associated with increased TSP expression; ras transfection, which results in increased tumorigenesis, is associated with decreased TSP expression. (C) 1994 Wiley-Liss, Inc.* C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 22 TC 185 Z9 192 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 OCT 15 PY 1994 VL 59 IS 2 BP 191 EP 195 DI 10.1002/ijc.2910590209 PG 5 WC Oncology SC Oncology GA PM265 UT WOS:A1994PM26500008 PM 7927918 ER PT J AU SULLIVAN, FJ HERSCHER, LL COOK, JA SMITH, J STEINBERG, SM EPSTEIN, AH OLDFIELD, EH GOFFMAN, TE KINSELLA, TJ MITCHELL, JB GLATSTEIN, E AF SULLIVAN, FJ HERSCHER, LL COOK, JA SMITH, J STEINBERG, SM EPSTEIN, AH OLDFIELD, EH GOFFMAN, TE KINSELLA, TJ MITCHELL, JB GLATSTEIN, E TI NATIONAL-CANCER-INSTITUTE (PHASE-II) STUDY OF HIGH-GRADE GLIOMA TREATED WITH ACCELERATED HYPERFRACTIONATED RADIATION AND IODODEOXYURIDINE - RESULTS IN ANAPLASTIC ASTROCYTOMA SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 11-15, 1993 CL NEW ORLEANS, LA SP AMER SOC THERAPEUT RADIOL & ONCOL DE HIGH-GRADE GLIOMA; RADIATION THERAPY; IODODEOXYURIDINE; RADIATION SENSITIZERS ID THERAPY-ONCOLOGY-GROUP; CONTINUOUS INTRAVENOUS INFUSIONS; HYPOXIC CELL RADIOSENSITIZERS; BONE-MARROW TRANSPLANTATION; CENTRAL NERVOUS-SYSTEM; GLIOBLASTOMA-MULTIFORME; MALIGNANT GLIOMAS; BRAIN-TUMORS; CLINICAL RADIOSENSITIZER; HALOGENATED PYRIMIDINES AB Purpose: We report the outcome of a Phase II study of a cohort of patients with high-grade glioma treated with accelerated hyperfractionated radiation and the radiation sensitizer, iododeoxyuridine (IdUrd). Methods and Materials: Between January 1988 and December 1990, 39 consecutive patients with high-grade glioma were enrolled and treated on a Phase II protocol including hyperfractionated radiation and IdUrd. Thirty-two patients were male and seven were female. Age range was 19 to 71 years with a median age of 38 years. IdUrd (1000 mg/m(2) per day) was administered in two separate 14-day courses, the first during the initial radiation field and the second during the final cone-dean field. All patients were treated consistently with partial brain technique and received 1.5 Gy/fraction twice daily to a mean total dose of 71.25 Gy (range 66-72 Gy excluding one patient who did not complete treatment). The initial field was treated to 45 Gy followed by a cone-down field covering the tumor volume plus a 1-cm margin to the final dose. Patients were assessed for acute and long-term morbidity and followed for outcome. Two patients had biopsies during the course of treatment. Flow cytometry and high performance liquid chromatography was used to evaluate the labeling index and the percent replacement of IdUrd in the biopsy specimen. Results: Thirty-eight of 39 patients completed therapy. One patient died on treatment at 48 Gy and is included in the survival analysis. No patient was lost to follow-up. Twenty-one patients had Grade 3 (anaplastic astrocytoma) tumors and 18 patients had Grade 4 (glioblastoma multiforme). Median survival for the entire cohort was 23 months. For the glioblastoma multiforme patients, median survival was 15 months. The median survival of the anaplastic astrocytoma patients has not yet been reached. In the patients assessed, the range of IdUrd tumor cell incorporation was only 0-2.4%. Conclusion: Accelerated hyperfractionated radiation therapy with IdUrd was administered with acceptable acute toxicity. The major acute side effects of mucositis and thrombocytopenia were related to IdUrd infusion and were dose-dependent. There were no unacceptable acute toxicities referable to the radiation as delivered. With a median potential follow-up of 51 months, the actuarial median survival of the glioblastoma multiforme patients is comparable with the best previously published reports. The outcome of patients with anaplastic astrocytoma compares very favorably with even the most aggressive multi-modality approaches in the recent literature with a minimum of acute morbidity. C1 NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NIH,DEPT NEUROL SURG,BETHESDA,MD 20892. UNIV WISCONSIN,SCH MED,DEPT HUMAN ONCOL,MADISON,WI. SIMMONS CANC CTR,DALLAS,TX. RP SULLIVAN, FJ (reprint author), NCI,RADIAT ONCOL BRANCH,BLDG 10,ROOM B3B69,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 64 TC 55 Z9 56 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 15 PY 1994 VL 30 IS 3 BP 583 EP 590 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA PK604 UT WOS:A1994PK60400008 PM 7928489 ER PT J AU YOUNG, HA GHOSH, P YE, JP LEDERER, J LICHTMAN, A GERARD, JR PENIX, L WILSON, CB MELVIN, AJ MCGURN, ME LEWIS, DB TAUB, DD AF YOUNG, HA GHOSH, P YE, JP LEDERER, J LICHTMAN, A GERARD, JR PENIX, L WILSON, CB MELVIN, AJ MCGURN, ME LEWIS, DB TAUB, DD TI DIFFERENTIATION OF THE T-HELPER PHENOTYPES BY ANALYSIS OF THE METHYLATION STATE OF THE IFN-GAMMA GENE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LARGE GRANULAR LYMPHOCYTES; IMMUNE INTERFERON GENE; DNA METHYLTRANSFERASE; CELL LINES; EXPRESSION; INTERLEUKIN-2; ACTIVATION; INDUCTION; PROTEIN; SEQUENCE AB Th1 and Th2 CD4(+) T cell clones have been defined by their ability to produce different lymphokines. However, the processes by which CD4(+) T cells differentially regulate lymphokine gene expression have not been well defined. In this report, we demonstrate that the methylation status of a CpG dinucleotide contained within a TATA proximal regulatory element of the IFN-gamma promoter correlates with the transcription of the gene. In murine Th1 clones and two human CD4(+) Th0 clones, this site is either completely or partially hypomethylated, whereas in murine Th2 clones this site is >98% methylated. Treatment of murine Th2 clones with 5-azacytidine, an agent that inhibits methylation of the DNA, converts these cells to IFN-gamma producers. Additional targets for methylation outside the transcriptional control regions of the IFN-gamma genetic locus were found to be hypomethylated in Th2 cells but not in Th1 cells. Electrophoretic mobility shift assays (EMSA) revealed at least five distinct protein-DNA complexes that are formed with an oligonucleotide containing the IFN-gamma promoter TATA proximal regulatory element, and in vitro methylation of this site results in a loss of these three complexes. Furthermore, a comparison of nuclear extracts prepared from Th1 and Th2 clones revealed that the EMSA patterns were qualitatively similar but differed quantitatively. In addition, transient transfection of a murine IFN-gamma promoter-chloramphenicol acetyl transferase (CAT) gene construct into both Th1 and Th2 clones produced CAT activity that was not inducible by anti-CD3, indicating that hypomethylation per se of the promoter alone is not sufficient for inducible gene expression. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. UNIV WASHINGTON,DEPT PEDIAT,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT IMMUNOL,SEATTLE,WA 98195. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. RP YOUNG, HA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,BLDG 560,FREDERICK,MD 21702, USA. NR 32 TC 152 Z9 154 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 1994 VL 153 IS 8 BP 3603 EP 3610 PG 8 WC Immunology SC Immunology GA PM581 UT WOS:A1994PM58100026 PM 7523497 ER PT J AU ROSENBERG, PS AF ROSENBERG, PS TI BACKCALCULATION MODELS OF AGE-SPECIFIC HIV INCIDENCE RATES SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT 13th Research Application Conference on Quantitative Methods for Studying AIDS CY JUN 14-18, 1993 CL UNIV TUBINGEN, CONF CTR SOCIAL SCI, BLAUBEUREN, GERMANY SP SOCIETAL INST MATH SCI HO UNIV TUBINGEN, CONF CTR SOCIAL SCI ID UNITED-STATES; INCUBATION PERIOD; HOMOSEXUAL MEN; AIDS INCIDENCE; INFECTION; PREVALENCE; EPIDEMIC; THERAPY; TRENDS; COHORT AB This paper extends the use of backcalculation to estimate past incidence of HIV infection in different age groups from age-specific counts of AIDS incidence. The approach is flexible and allows the distribution of age at HIV infection to change over time. In this new approach, the incubation distributions used to backcalculate HIV infection rates depend on the age at HIV infection, because younger age is associated with slower progression. The effect of age on progression is estimated from a joint analysis of natural history data from several cohort studies of gay and bisexual men. As in previous applications, the incubation distributions also change over time to accommodate treatment effects and the 1987 revision of the surveillance definition. The method is applied to AIDS incidence data for the United States population. Estimated infection incidence for the entire population declined from peak levels seen in the mid-1980s. However, persons under age 25 years have accounted for an increasing proportion of new HIV infections as the epidemic has progressed. Quantitative estimates were sensitive to the assumed incubation distribution, but the trend toward younger age at HIV infection was apparent using several models of the incubation distribution. Although the models are computationally intensive, they provide useful information about seroincidence trends in different age groups. RP ROSENBERG, PS (reprint author), NCI,EPIDEMIOL METHODS SECT,6130 EXECUT BLVD,EPN-403,ROCKVILLE,MD 20892, USA. NR 31 TC 30 Z9 30 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD OCT 15 PY 1994 VL 13 IS 19-20 BP 1975 EP 1990 DI 10.1002/sim.4780131909 PG 16 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA PQ293 UT WOS:A1994PQ29300008 PM 7846404 ER PT J AU NEATON, JD WENTWORTH, DN RHAME, F HOGAN, C ABRAMS, DI DEYTON, L AF NEATON, JD WENTWORTH, DN RHAME, F HOGAN, C ABRAMS, DI DEYTON, L TI CONSIDERATIONS IN CHOICE OF A CLINICAL END-POINT FOR AIDS CLINICAL-TRIALS SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT 13th Research Application Conference on Quantitative Methods for Studying AIDS CY JUN 14-18, 1993 CL UNIV TUBINGEN, CONF CTR SOCIAL SCI, BLAUBEUREN, GERMANY SP SOCIETAL INST MATH SCI HO UNIV TUBINGEN, CONF CTR SOCIAL SCI ID IMMUNODEFICIENCY-VIRUS INFECTION; ASYMPTOMATIC HIV-INFECTION; PLACEBO-CONTROLLED TRIAL; FAILURE TIME DATA; REGRESSION-ANALYSIS; MULTIPLE ENDPOINTS; CUBIC MILLIMETER; INOSINE PRANOBEX; ZIDOVUDINE AZT; DOUBLE-BLIND AB In most clinical trials of antiretroviral therapy for patients infected with HIV, the major outcome variable has been the combined clinical endpoint of any new or recurrent AIDS defining event. We review features of combined endpoints and use data from the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) to evaluate this outcome measure in terms of relevance, diagnostic certainty and sensitivity. We conclude that this endpoint is not relevant because: (i) the 19 different events constituting the combined endpoint are equally weighted in analyses even though they vary considerably in terms of risk of death; and (ii) events after the first are ignored, thus the event profile of patients is not taken into account in making treatment comparisons. We also conclude that power may be low with use of this endpoint if treatments under study do not have an immediate impact on disease progression, if some events which occur soon after randomization represent a disease process that has already begun to incubate, or if treatment differences for the various events constituting the combined endpoint are differentially effected by treatment. Since the ease and certainty of diagnosis of each of the 19 events also vary, we recommend that survival be the primary endpoint of antiretroviral trials, and that all opportunistic events experienced by patients, not just the first, be collected and summarized. Trial reports should include comparisons of incidence of each event by treatment group so that readers can rank events as they please. A single summary measure which considers severity and the entire event profile, as described here, would also be useful for assessing the impact of treatments on quality of life. Further research on approaches for weighting and combining multiple outcome measures is needed. C1 UNIV MINNESOTA,DEPT MED,DIV INFECT DIS,MINNEAPOLIS,MN. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO COMMUNITY CONSORTIUM AIDS,SAN FRANCISCO,CA. NIAID,DIV AIDS,BETHESDA,MD 20892. RP NEATON, JD (reprint author), UNIV MINNESOTA,SCH PUBL HLTH,DIV BIOSTAT,2221 UNIV AVE SE,ROOM 200,MINNEAPOLIS,MN 55414, USA. NR 49 TC 61 Z9 62 U1 1 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD OCT 15 PY 1994 VL 13 IS 19-20 BP 2107 EP 2125 DI 10.1002/sim.4780131919 PG 19 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA PQ293 UT WOS:A1994PQ29300018 PM 7846414 ER PT J AU RIDA, WN LAWRENCE, DN AF RIDA, WN LAWRENCE, DN TI SOME STATISTICAL ISSUES IN HIV VACCINE TRIALS SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT 13th Research Application Conference on Quantitative Methods for Studying AIDS CY JUN 14-18, 1993 CL UNIV TUBINGEN, CONF CTR SOCIAL SCI, BLAUBEUREN, GERMANY SP SOCIETAL INST MATH SCI HO UNIV TUBINGEN, CONF CTR SOCIAL SCI ID IMMUNODEFICIENCY-VIRUS TYPE-1; ANTIBODY-DEPENDENT ENHANCEMENT; PROTECTIVE EFFICACY; SUBUNIT VACCINES; RISK POPULATIONS; CLINICAL-TRIALS; INFECTION; AIDS; MACAQUES; PREVENTION AB Efficacy trials of prophylactic HIV vaccines will be among the most difficult clinical trials ever attempted. Not only will there be challenges with the recruitment and retention of high-risk uninfected individuals, there will be many statistical challenges to the design, conduct, analysis, and interpretation of these trials. General features of an efficacy trial are described, including choice for the primary endpoint and testing for and estimating vaccine efficacy. Secondary objectives of trials are also discussed. These include determining the correlates of protective immunity, assessing the impact of HIV genetic variation on vaccine efficacy, and using biological markers such as viral load and CD4(+) lymphocyte cell count to gain insight on a vaccine's ability to prevent or delay disease. The use of biological markers as surrogates for disease outcome is discussed. Last, trial designs for studying several candidate vaccines or other HIV prevention strategies in a single trial are examined. C1 NIAID,DIV AIDS,VACCINE TRIALS & EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP RIDA, WN (reprint author), NIAID,DIV AIDS,BIOSTAT RES BRANCH,6003 EXEC BLVD,BETHESDA,MD 20892, USA. NR 70 TC 15 Z9 15 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD OCT 15 PY 1994 VL 13 IS 19-20 BP 2155 EP 2177 DI 10.1002/sim.4780131922 PG 23 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA PQ293 UT WOS:A1994PQ29300021 PM 7846417 ER PT J AU YOSHIMURA, K CHU, CS CRYSTAL, RG AF YOSHIMURA, K CHU, CS CRYSTAL, RG TI ENHANCER FUNCTION OF A 53-BP REPETITIVE ELEMENT IN THE 5' FLANKING REGION OF THE HUMAN NEUTROPHIL ELASTASE GENE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MAMMALIAN-CELLS; DNA-BINDING; EXPRESSION; SEQUENCE; EFFICIENT; PROTEINS; MYC AB Expression of the human neutrophil elastase (NE) gene is limited to the early stage of myeloid cell differentiation in bone marrow cells. While NE gene expression is controlled mainly at the transcriptional level during bone marrow cell differentiation, the mechanism of transcriptional control is not fully understood. One motif of interest in the 5' flanking region of the gene is the six tandem repeats of a 53-bp nucleotide sequence (REP53) containing a potential binding site for a basic helix-loop-helix protein located at -1032 to -716. The REP53 sequence can function as a non-cell specific transcriptional enhancer which is capable of augmenting heterologous promoter activity. When the single REP53 element was inserted into the pAZ1037 chloramphenicol acetyltransferase (CAT) expression vector immediately upstream of the chicken p-actin promoter in either normal or inverted orientation and used to transfect K-562 erythroleukemia or HeLa cervical carcinoma cells, these modified vectors achieved 2 to 3-fold higher CAT activity than the parental pAZ1037 vector irrespective of orientation of the REP53. C1 NHLBI,PULM BRANCH,BETHESDA,MD 20892. NEW YORK HOSP,CORNELL MED CTR,DIV PULM & CRIT CARE MED,NEW YORK,NY 10021. NR 24 TC 7 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 14 PY 1994 VL 204 IS 1 BP 38 EP 42 DI 10.1006/bbrc.1994.2422 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PM044 UT WOS:A1994PM04400006 PM 7945385 ER PT J AU BURKE, TR KOLE, HK ROLLER, PP AF BURKE, TR KOLE, HK ROLLER, PP TI POTENT INHIBITION OF INSULIN-RECEPTOR DEPHOSPHORYLATION BY A HEXAMER PEPTIDE-CONTAINING THE PHOSPHOTYROSYL MIMETIC F(2)PMP SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; SOLID-PHASE SYNTHESIS; SIGNAL TRANSDUCTION; IN-VITRO; ACTIVATION; ANALOGS; DRUG; PHOSPHORYLATION; CLEAVAGE; TARGETS AB Phosphonomethyl phenylalanine (Pmp) is a non-hydrolyzable phosphotyrosyl (pTyr) mimetic, which has been incorporated into eleven-mer Pmp-containing peptides that have previously been reported to competitively inhibit the protein-tyrosine phosphatases PTP1 and PTP 1B. We have recently shown that phosphonodifluoromethyl phenylalanine (F(2)Pmp) is superior to Pmp as a pTyr mimetic in SH2 domain-binding peptides. Herein we find using the hexameric peptide sequence Ac-D-A-D-E-X-L-amide, where X = (D/L)-Pmp or L-F(2)Pmp, that the half maximal inhibition values of these two peptides against PTP 1B-mediated dephosphorylation of autophosphorylated insulin receptor to be 200 mu M and 100 nM, respectively. These data indicate that F(2)Pmp induces a three orders of magnitude enhancement in affinity relative to Pmp, resulting in an exceptionally potent peptide-based PTP inhibitor. We conclude that F(2)Pmp may be a generally useful tool in the preparation of selective, high affinity PTP inhibitors. (C) 1994 Academic Inc. C1 NIA,GERONTOL RES CTR,CLIN PHYSIOL LAB,DIABET UNIT,BALTIMORE,MD 21224. RP BURKE, TR (reprint author), NCI,DCT,MED CHEM LAB,DEV THERAPEUT PROGRAM,BLDG 37,RM 5C06,BETHESDA,MD 20892, USA. RI Burke, Terrence/N-2601-2014 NR 38 TC 207 Z9 210 U1 2 U2 12 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 OCT 14 PY 1994 VL 204 IS 1 BP 129 EP 134 DI 10.1006/bbrc.1994.2435 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PM044 UT WOS:A1994PM04400019 PM 7524496 ER PT J AU LIN, JJ NEWTON, DL MIKULSKI, SM KUNG, HF YOULE, RJ RYBAK, SM AF LIN, JJ NEWTON, DL MIKULSKI, SM KUNG, HF YOULE, RJ RYBAK, SM TI CHARACTERIZATION OF THE MECHANISM OF CELLULAR AND CELL-FREE PROTEIN-SYNTHESIS INHIBITION BY AN ANTITUMOR RIBONUCLEASE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID XENOPUS OOCYTES; P-30 PROTEIN; RNA; ANGIOGENIN AB Onconase, a protein with anti-tumor activity, causes potent inhibition of protein synthesis in the rabbit reticulocyte lysate (IC(50)10(-11)M) and when microinjected into Xenopus oocytes (IC(50)10(-10)M). Onconase is a member of the RNase A superfamily; however, unlike RNase A, the mechanism of protein synthesis inhibition does not involve apparent degradation of lysate or cellular ribosomal RNAs. Rather, reticulocyte and oocyte tRNA is hydrolyzed after Onconase treatment. Furthermore, re-addition of tRNA to Onconase pretreated lysates or oocytes restores the translational capacity of the system. Taken together these results suggest that Onconase causes potent protein synthesis inhibition by a mechanism involving inactivation Of cellular tRNA. (C) 1994 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BCDP,FREDERICK,MD 21702. ALFACELL CORP,BLOOMFIELD,NJ 07003. NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. RP LIN, JJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,DCT,BIOCHEM PHYSIOL LAB,FREDERICK,MD 21702, USA. NR 11 TC 47 Z9 49 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 OCT 14 PY 1994 VL 204 IS 1 BP 156 EP 162 DI 10.1006/bbrc.1994.2439 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PM044 UT WOS:A1994PM04400023 PM 7945354 ER PT J AU LIN, KH LIN, YW PARKISON, C CHENG, SY AF LIN, KH LIN, YW PARKISON, C CHENG, SY TI STIMULATION OF PROLIFERATION BY 3,3',5-TRIIODO-L-THYRONINE IN POORLY DIFFERENTIATED HUMAN HEPATOCARCINOMA CELLS OVEREXPRESSING BETA-1 THYROID-HORMONE RECEPTOR SO CANCER LETTERS LA English DT Article DE THYROID HORMONE; T-3 RECEPTOR; CARCINOGENESIS; HEPATOCARCINOMA; GROWTH AND DIFFERENTIATION ID INDUCTION; GROWTH; RAT AB To understand the role of thyroid hormone nuclear receptors (TRs) in hepatocarcinogenesis, we characterized the TRs in nine human hepatocarcinoma cell lines. The expression of TR proteins is receptor subtype- and cell type dependent. TR alpha 1 protein expresses similarly at a low level in each of the nine cell lines. In contrast, TR beta 1 is overexpressed in hepatocarcinoma cells which are poorly differentiated. Furthermore, thyroid hormone was found to stimulate the proliferation of cells in which TR beta 1 is overexpressed. These results suggest that TR beta 1 is most likely involved in the differentiation and proliferation of hepatocarcinoma cells. Our studies have shed new light in the understanding of the role of TRs in liver carcinogenesis. C1 NCI,DCBDC,MOLEC BIOL LAB,BETHESDA,MD 20892. RP LIN, KH (reprint author), CHANG GUNG COLL MED & TECHNOL,GRAD INST CLIN MED,259 WEN HWA 1ST RD,TAYUAN,TAIWAN. NR 12 TC 25 Z9 26 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD OCT 14 PY 1994 VL 85 IS 2 BP 189 EP 194 DI 10.1016/0304-3835(94)90274-7 PG 6 WC Oncology SC Oncology GA PT739 UT WOS:A1994PT73900008 PM 7954336 ER PT J AU SPREAFICO, R FRASSONI, C ARCELLI, P BATTAGLIA, G WENTHOLD, RJ DEBIASI, S AF SPREAFICO, R FRASSONI, C ARCELLI, P BATTAGLIA, G WENTHOLD, RJ DEBIASI, S TI DISTRIBUTION OF AMPA SELECTIVE GLUTAMATE RECEPTORS IN THE THALAMUS OF ADULT-RATS AND DURING POSTNATAL-DEVELOPMENT - A LIGHT AND ULTRASTRUCTURAL IMMUNOCYTOCHEMICAL STUDY SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE RECEPTOR; GLUTAMATE; NON-NMDA; ONTOGENY; THALAMUS; ELECTRON MICROSCOPY ID AMINO-ACID RECEPTORS; CENTRAL-NERVOUS-SYSTEM; METHYL-D-ASPARTATE; NON-NMDA RECEPTORS; SUBCELLULAR-LOCALIZATION; DIFFERENTIAL EXPRESSION; SYNAPTIC TRANSMISSION; INSITU HYBRIDIZATION; VENTROBASAL THALAMUS; MONOCLONAL-ANTIBODY AB The regional, cellular and subcellular distribution of AMPA receptors was demonstrated immunocytochemically within the thalamus of adult and young (from 1 to 20 days postnatal, P-1-P-20) rats. The antipeptide antibodies used(37) recognize individual subunit proteins of the AMPA-preferring glutamate receptor, i.e., GluR1, GluR2-3 and GluR4. Our results demonstrate that these AMPA receptor subunits are generally not highly expressed in the thalamus, as compared to other brain:areas and that they are enriched differentially within different thalamic nuclei. GluR1 is mostly found in intralaminar and midline nuclei throughout life, whereas GluR2-3 is moderately expressed in the thalamus, with no;major developmental changes. GluR4 is the predominant subunit expressed in the reticular nucleus in adult rats, but not in young animals, where until P-9 it is instead present in the ventrobasal complex. Samples of paraventricular and lateral geniculate nuclei stained with GluR1 and of reticular nucleus as well as ventrobasal complex stained with GluR4 were used for the ultrastructural study; In all the samples, labelling was in the somatic and dendritic cytoplasm, with dense patches of reaction product apposing post-synaptic densities of terminals with round clear vesicles and asymmetric specializations. Glial staining was observed only with the GluR1 antiserum and there was no evidence of labelled synaptic terminals. The differential distribution of GluR subunits in the thalamus suggests that certain subunits may participate more than others in mediating post-synaptic responses in distinct neuronal populations and also that other GluR types may be involved in the thalamic networks. C1 UNIV MILAN,SEZ ISTOL & ANAT UMANA,DIPARTIMENTO FISIOL & BIOCHIM GEN,MILAN,ITALY. NIDOCD,NEUROCHEM LAB,BETHESDA,MD 20892. RP SPREAFICO, R (reprint author), IST NAZL NEUROL C BESTA,DIPARTIMENTO NEUROFISIOL,VIA CELORIA 11,I-20133 MILAN,ITALY. RI Spreafico, Roberto/K-2301-2016 OI Frassoni, Carolina/0000-0002-9300-5139; Spreafico, Roberto/0000-0002-6528-1240 NR 59 TC 45 Z9 45 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD OCT 14 PY 1994 VL 82 IS 1-2 BP 231 EP 244 DI 10.1016/0165-3806(94)90166-X PG 14 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA PM494 UT WOS:A1994PM49400025 ER PT J AU PATTERTON, D SHI, YB AF PATTERTON, D SHI, YB TI THYROID HORMONE-DEPENDENT DIFFERENTIAL REGULATION OF MULTIPLE ARGINASE GENES DURING AMPHIBIAN METAMORPHOSIS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID XENOPUS-LAEVIS; NUCLEOTIDE-SEQUENCE; LIVER ARGINASE; MAMMARY-GLAND; RECEPTOR; TISSUES; EXPRESSION; LARVAL; CDNA AB We have cloned three nonhepatic arginase genes in Xenopus laevis. The deduced amino acid sequences of the three arginases are almost identical and share about 60% identity with mammalian as well as Xenopus liver arginase, Both the liver and nonhepatic arginase genes are activated early during embryogenesis. The liver arginase gene is strongly expressed in tadpole liver, but weakly in other tissues. In contrast, the nonhepatic arginase genes have the strongest expression in the tadpole tail. During metamorphosis, the liver and nonhepatic arginase genes show distinct regulation patterns. In the intestine, both types of arginase genes are activated during the remodeling period. In the tail, the liver arginase gene is activated during tail resorption, whereas the nonhepatic ones are highly expressed throughout all stages examined. Finally, in the hindlimb, the liver arginase is up-regulated slightly during development, whereas the nonhepatic ones have low levels of expression until the end of metamorphosis. During 3,5,3'-L-triiodothyronine (T-3)-induced metamorphosis, the nonhepatic arginase genes are activated very quickly, whereas the liver arginase gene is a late T-3 response gene. These differential regulation patterns during normal and T-3-induced metamorphosis suggest potential functions for the arginases during tissue remodeling. C1 NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. NR 38 TC 39 Z9 43 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 14 PY 1994 VL 269 IS 41 BP 25328 EP 25334 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ491 UT WOS:A1994PQ49100017 PM 7929226 ER PT J AU LEE, CW LEE, KH LEE, SB PARK, D RHEE, SG AF LEE, CW LEE, KH LEE, SB PARK, D RHEE, SG TI REGULATION OF PHOSPHOLIPASE C-BETA-4 BY RIBONUCLEOTIDES AND THE ALPHA-SUBUNIT OF G(Q) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-GAMMA-SUBUNITS; LIGHT-MEDIATED BREAKDOWN; RECOMBINANT-GQ-ALPHA; ROD OUTER SEGMENTS; G-PROTEIN; C ISOZYMES; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; LIMULUS PHOTORECEPTORS; NORPA GENE; SF9 CELLS AB The fourth member of mammalian beta-type phospholipase C isozymes, PLC-beta 4, was recently purified from bovine retina, and the corresponding cDNA was cloned from rat brain and sequenced. PLC-beta 4 has now been shown to differ from the other three mammalian beta-type isozymes (PLC-beta 1, -beta 2, and -beta 3) in that it is selectively inhibited by ribonucleotides. The inhibition requires the 5'-phosphate and 2'-hydroxyl groups of ribose as well as the base moiety. Thus, deoxyribonucleotides and ribose B-phosphate were not inhibitory. The monophosphate, diphosphate, and triphosphate nucleoside derivatives were all inhibitory, whereas cyclic nucleotides were ineffective. Purine nucleotides were more potent inhibitors than pyrimidine nucleotides; the 50% inhibitory concentrations were 20-30 mu M for AMP and GMP, and 100-200 mu M for UMP and CMP. Unlike the other beta-type isozymes, PLC-beta 4 contains the GX(4)GKS consensus sequence for the recognition of the phosphoryl group of nucleotides. In the absence of ribonucleotides, the specific activity of PLC-beta 4 toward phosphatidylinositol 4,5-bisphosphate was four to five times the average specific activity of PLC-beta 1 and PLC-beta 3. Thus, nucleotide-dependent inhibition may serve to reduce the activity of PLC-beta 4 in the absence of a hormonal signal. The regulation of PLC-beta 4 by G-proteins was also studied. Similar to the other three PLC-beta isozymes, PLC-beta 4 was activated by the alpha subunit of G(q) but not by the transducin alpha subunit. However, unlike other PLC-beta isozymes, PLC-beta 4 was not responsive to activation by G beta gamma subunits. C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NR 49 TC 81 Z9 83 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 14 PY 1994 VL 269 IS 41 BP 25335 EP 25338 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ491 UT WOS:A1994PQ49100018 PM 7929227 ER PT J AU OLAH, Z LEHEL, C ANDERSON, WB EIDEN, MV WILSON, CA AF OLAH, Z LEHEL, C ANDERSON, WB EIDEN, MV WILSON, CA TI THE CELLULAR RECEPTOR FOR GIBBON APE LEUKEMIA-VIRUS IS A NOVEL HIGH-AFFINITY SODIUM-DEPENDENT PHOSPHATE TRANSPORTER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ECOTROPIC RETROVIRUS RECEPTOR; AMINO-ACID TRANSPORTER; MURINE RETROVIRUSES; NUCLEOTIDE-SEQUENCE; NEUROSPORA-CRASSA; SURFACE RECEPTOR; GENE ENCODES; CELLS; INFECTION; SYSTEM AB The primate type C retrovirus gibbon ape leukemia virus (GaLV) has been shown to use a widely expressed, multiple membrane-spanning protein of unknown function as its cell surface receptor on human cells (GLVR1) (Johann, S. V., Gibbons, J. J., and O'Hara, B. (1992) J. Virol. 66, 1635-1640; O'Hara, B., Johann, S. V., Klinger, H. P., Blair, D. G., Rubinson, H., Dunni, K. J., Sass, P., Vitek, S. M., and Robins, T. (1990) Cell Growth Diff. 1, 119-127). Here we present evidence that the receptor for GaLV (GLVR1) functions as a sodium dependent transporter of inorganic phosphate. GLVR1 is shown to have approximately 3-4-fold higher affinity for phosphate than other mammalian phosphate transporters described to date. Productive infection of GLVR1-expressing cells by GaLV, but not other retroviruses, results in the complete blockade of GLVR1-specific uptake of inorganic phosphate. Since productive infection of cells with GaLV is generally not cytotoxic, it is likely that more than one phosphate transporter exists on the cell surface. Our data suggest that GLVR1 represents a sodium-dependent phosphate transporter that differs from other mammalian phosphate transporters in structure, affinity for phosphate, and function. C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NR 32 TC 140 Z9 143 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 OCT 14 PY 1994 VL 269 IS 41 BP 25426 EP 25431 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ491 UT WOS:A1994PQ49100033 PM 7929240 ER PT J AU KASHIWAYA, Y SATO, K TSUCHIYA, N THOMAS, S FELL, DA VEECH, RL PASSONNEAU, JV AF KASHIWAYA, Y SATO, K TSUCHIYA, N THOMAS, S FELL, DA VEECH, RL PASSONNEAU, JV TI CONTROL OF GLUCOSE-UTILIZATION IN WORKING PERFUSED RAT-HEART SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FLUX CONTROL COEFFICIENTS; SKELETAL-MUSCLE HEXOKINASE; METABOLIC CONTROL ANALYSIS; TRICARBOXYLIC-ACID CYCLE; FRUCTOSE 2,6-BISPHOSPHATE; DICTYOSTELIUM-DISCOIDEUM; TRANSPORTER GLUT4; LIVER CELLS; GLYCOLYSIS; KINETICS AB Metabolic control analyses of glucose utilization were performed for four groups of working rat hearts perfused with Krebs-Henseleit buffer containing 10 mu M glucose only, or with the addition of 4 mM D-beta-hydroxybutyrate/1 mM acetoacetate, 100 ana insulin (0.05 unit/ml), or both. Net glycogen breakdown occurred in the glucose group only and was converted to net glycogen synthesis in the presence of all additions. The flux of [2-H-3]glucose through P-glucoisomerase (EC 5.3.1.9) was reduced with ketones, elevated with insulin, and unchanged with the combination. Net glycolytic flux was reduced in the presence of ketones and the combination. The flux control coefficients were determined for the portion of the pathway involving glucose transport to the branches of glycogen synthesis and glycolysis. Major control was divided between the glucose transporter and hexokinase (EC 2.7.1.1) in the glucose group. The distribution of the control was slightly shifted to hexokinase with ketones, and control at the glucose transport step was abolished in the presence of insulin. Analysis of the pathway from 3-P-glycerate to pyruvate determined that the major control was shared by enolase (EC 4.2.1.1) and pyruvate kinase (EC 2.7.1.40) in the glucose group. Addition of ketones, insulin, or the combination shifted the control to P-glycerate mutase (EC 5.4.2.1) and pyruvate kinase. These results illustrate that the control of the metabolic flux in glucose metabolism of rat heart is not exerted by a single enzyme but variably distributed among enzymes depending upon substrate availability, hormonal stimulation, or other changes of conditions. C1 NIAAA,ROCKVILLE,MD 20852. OXFORD BROOKES UNIV,SCH BIOL & MOLEC SCI,OXFORD OX3 0BP,ENGLAND. RI Fell, David/B-2109-2009 OI Fell, David/0000-0001-6669-2247 NR 82 TC 215 Z9 217 U1 1 U2 8 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 OCT 14 PY 1994 VL 269 IS 41 BP 25502 EP 25514 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ491 UT WOS:A1994PQ49100044 PM 7929251 ER PT J AU CHIAVAROLI, C BIRD, GS PUTNEY, JW AF CHIAVAROLI, C BIRD, GS PUTNEY, JW TI DELAYED ALL-OR-NONE ACTIVATION OF INOSITOL 1,4,5-TRISPHOSPHATE-DEPENDENT CALCIUM SIGNALING IN SINGLE-RAT HEPATOCYTES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LACRIMAL ACINAR-CELLS; PERMEABILIZED HEPATOCYTES; STIMULATED HEPATOCYTES; CA2+ MOBILIZATION; OSCILLATIONS; VASOPRESSIN; RELEASE; FURA-2; SEQUESTRATION; SECRETION AB When single rat hepatocytes were stimulated with the phospholipase C-activating hormone, vasopressin (from 300 pM to 1 mu M), the [Ca2+](i) signals were always ''all-or-none'' responses. At low concentrations of vasopressin, Ca2+ release was maximal because liberation of additional inositol 1,4,5-trisphosphate (IP3) by photolysis of its caged precursor at the top of the [Ca2+](i) spike failed to increase [Ca2+](i) further. However, if IP3 was generated by photolysis of caged IP3 in previously unstimulated cells, [Ca2+](i) increased immediately, and the magnitude of the response was a graded function of the quantity of IP3 released. We also analyzed the kinetics of activation of intracellular IP3 receptor/Ca2+ channels by monitoring the quench of sequestered dye by the entry of cytoplasmic Mn2+ into fura-2-loaded intracellular IP3-sensitive organelles. This Mn2+-induced quench was precipitous and always preceded by a delay inversely related to the vasopressin concentration. In hepatocytes stimulated with 10 nM vasopressin, IP3 increased slowly, and the half-time of the IP3 rise was comparable with the latency for the release of intracellular calcium. The slow rise in IP3 would be predicted to produce accelerating Ca2+ release. This is consistent with the results of the Mn2+ quench experiments, which revealed accelerating activation of intracellular IP3-regulated calcium channels. We conclude that this accelerating release of Ca2+, which does not occur with instantaneous increases in IP3 due to flash photolysis, is likely to be important for generating the all-or-none Ca2+ mobilization that initiates the processes of intracellular [Ca2+](i) oscillations. RP CHIAVAROLI, C (reprint author), NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709, USA. NR 25 TC 39 Z9 40 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 OCT 14 PY 1994 VL 269 IS 41 BP 25570 EP 25575 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ491 UT WOS:A1994PQ49100053 PM 7523388 ER PT J AU BUBB, MR LEWIS, MS KORN, ED AF BUBB, MR LEWIS, MS KORN, ED TI ACTOBINDIN BINDS WITH HIGH-AFFINITY TO A COVALENTLY CROSS-LINKED ACTIN DIMER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACANTHAMOEBA-CASTELLANII; POLYMERIZATION; PURIFICATION; GELSOLIN; PROTEIN; MOTIF AB Actobindin, a 9.8-kDa protein purified from Acanthamoeba castellanii, contains two actin-binding sites that can simultaneously bind two actin monomers. However, actobindin inhibits actin polymerization to a greater extent than can be explained by its affinity for actin monomers (site specific K-D = 3.3 mu M). This paradox would be resolved if actobindin could interfere with the nucleation phase of polymerization by using both binding sites to bind simultaneously to an actin oligomer because the interaction with oligomer would be thermodynamically favored over that with actin monomer. We now show that a covalently cross-linked actin dimer prepared from cross linked F-actin binds to actobindin with high affinity (apparent K-D = 11 nM) in accordance with theoretical predictions for simultaneous binding of two actin subunits per single actobindin and consistent with the hypothesis that actobindin might bind to native actin oligomers and prevent them from nucleating polymerization. Furthermore, the interaction with cross-linked dimer exhibits specificity in that an isomeric cross-linked actin dimer with more rapid electrophoretic mobility binds weakly to actobindin. However, only this isomeric dimer is produced when cross-linking reagents are added to actin undergoing polymerization in the presence of actobindin. Therefore, if actobindin inhibits polymerization by interacting with a native dimer whose conformation is similar to that of the cross-linked dimer with slower electrophoretic mobility, then actobindin must either block the cross linking sites or convert the dimer to a different conformation. C1 NHLBI, CELL BIOL LAB, BETHESDA, MD 20892 USA. NIH, NATL CTR RES RESOURCES, BIOMED ENGN & INSTRUMENTAT PROGRAM, BETHESDA, MD 20892 USA. RI Korn, Edward/F-9929-2012 NR 16 TC 15 Z9 15 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 14 PY 1994 VL 269 IS 41 BP 25587 EP 25591 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ491 UT WOS:A1994PQ49100056 PM 7929261 ER PT J AU BUBB, MR KNUTSON, JR PORTER, DK KORN, ED AF BUBB, MR KNUTSON, JR PORTER, DK KORN, ED TI ACTOBINDIN INDUCES THE ACCUMULATION OF ACTIN DIMERS THAT NEITHER NUCLEATE POLYMERIZATION NOR SELF-ASSOCIATE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACANTHAMOEBA-CASTELLANII; MONOMERIC ACTIN; FLUORESCENCE; BINDING; DIFFUSION; SPECTROSCOPY; INHIBITION AB Actobindin purified from Acanthamoeba castellanii inhibits the nucleation, but not the elongation, phase of actin polymerization. Previously, we had speculated that actobindin, which can simultaneously bind two actin monomers (Bubb, M. R., Lewis, M. S., and Kern, E. D. (1991) J. Biol. Chem. 266, 3820-3826), might preferentially interact with small oligomers and inhibit their ability to elongate (Lambooy, P. K., and Kern, E. D. (1988) J. Biol. Chem. 263, 12836-12843). In the accompanying paper (Bubb, M. R., Lewis, M. S., and Kern, E. D. (1994) J. Biol. Chen. 269, 25587-25591), we show that under non-polymerizing conditions, actobindin binds to covalently cross-linked actin dimers with higher affinity than to two actin monomers, The sedimentation velocity and fluorescence anisotropy experiments described in this paper show that actobindin prevents the formation of actin oligomers larger than an actin dimer under conditions in which, in the absence of actobindin, actin rapidly polymerizes to F-actin with no detectable small oligomers. Moreover, the molar concentration of actin dimer formed in the presence of actobindin can exceed the total actobindin concentration. These results indicate that actobindin does not form a stable complex with native actin dimer but, rather, causes the accumulation of dimers that are unable to nucleate polymerization or self-associate. C1 NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. RI Korn, Edward/F-9929-2012 NR 28 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 14 PY 1994 VL 269 IS 41 BP 25592 EP 25597 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ491 UT WOS:A1994PQ49100057 PM 7929262 ER PT J AU MODARRESS, KJ CAVANAUGH, AH CHAKRABORTI, PK SIMONS, SS AF MODARRESS, KJ CAVANAUGH, AH CHAKRABORTI, PK SIMONS, SS TI METAL OXYANION STABILIZATION OF THE RAT GLUCOCORTICOID RECEPTOR IS INDEPENDENT OF THIOLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEAT-SHOCK PROTEIN; DNA-BINDING DOMAIN; CALF THYMUS DNA; STEROID-BINDING; PROGESTERONE-RECEPTOR; SULFHYDRYL-GROUPS; 59-KILODALTON PROTEIN; MONOCLONAL-ANTIBODY; COMPLEX; MOLYBDATE AB The ability of sodium molybdate, both to stabilize the steroid binding activity of glucocorticoid receptors and to prevent the activation of receptor-steroid complexes to a DNA binding species, has long been thought to involve thiols. Two receptor thiols in particular, Cys-656 and Cys-661 of rat receptors, have been suspected. The requirements for the action of molybdate, as well as two other metal oxyanions (tungstate and vanadate) known to exert the same effects as molybdate, have now been examined with receptors in which these thiols, or a third cysteine in the steroid binding cavity (Cys-640), have been mutated to serine. No mutation prevented any metal oxyanion from either stabilizing steroid-free receptors or blocking the activation of complexes for binding to nonspecific or specific DNA sequences. Thus, Cys-640, Cys-656, and Cys-661 are not required for any of the effects of molybdate, tungstate, or vanadate with rat glucocorticoid receptors. Studies with hybrid receptors, and with a 16-kDa steroid binding core fragment containing only 3 cysteines at positions 640, 656, and 661, indicated that no cysteine of the rat receptor was needed to maintain responsiveness to molybdate. Even when all of the thiol groups in crude cytosol were blocked by reaction with excess methyl methanethiol-sulfonate, each metal oxyanion was still able to stabilize the steroid binding of receptors. These results argue that molybdate, tungstate, and vanadate each interact with the receptor or an associated nonreceptor protein(s) in a manner that does not require thiols. An indirect mechanism of molybdate action was evaluated in light of the recent report that the whole cell actions are mediated by increased levels of intracellular cGMP. Under cell-free conditions, however, the effects of molybdate could not be reproduced by cGMP derivatives. Evidence consistent with a direct effect was that molybdate, tungstate, or vanadate each modified the kinetics of proteolysis of wild type receptors at 0 degrees C by trypsin, presumably due to induced conformational changes of the receptor. This alteration of trypsin digestion constitutes yet another effect of metal oxyanions on the glucocorticoid receptor. C1 NIDDK,LMCB,STEROID HORMONE SECT,BETHESDA,MD 20892. NR 76 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 14 PY 1994 VL 269 IS 41 BP 25621 EP 25628 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ491 UT WOS:A1994PQ49100061 PM 7929266 ER PT J AU DANCIS, A HAILE, D YUAN, DS KLAUSNER, RD AF DANCIS, A HAILE, D YUAN, DS KLAUSNER, RD TI THE SACCHAROMYCES-CEREVISIAE COPPER TRANSPORT PROTEIN (CTR1P) - BIOCHEMICAL, CHARACTERIZATION, REGULATION BY COPPER, AND PHYSIOLOGICAL-ROLE IN COPPER UPTAKE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CU,ZN SUPEROXIDE-DISMUTASE; WILSON DISEASE GENE; IRON UPTAKE; METALLOTHIONEIN GENE; FERRIC REDUCTASE; YEAST; EXPRESSION; METABOLISM; MUTANTS; ENCODES AB The CTR1 gene of Saccharomyces cerevisiae encodes a protein required for high affinity copper uptake. The protein is expressed on the plasma membrane, is heavily glycosylated with O-linkages, and exists as an oligomer in vivo. The transcript abundance is strongly regulated by copper availability, being induced by copper deprivation and repressed by copper excess. Regulation occurs at very low, nontoxic levels of available copper and is independent of ACE1, the trans-inducer of yeast metallothionein. Expression of Ctr1p is limiting for copper uptake, since overexpression from a 2 mu high copy number plasmid increases copper uptake. Mutations in CTR1 result in altered cellular responses to extracellular copper, demonstrating a physiologic role for CTR1 in the delivery of copper to the cytosol. A copper dependent reporter gene construct, CUP1-lacZ, is not expressed in CTR1 mutants to the same level as in wild-type strains, and Cu,Zn superoxide dismutase activity is deficient in these mutants. The growth arrest that occurs in CTR1 mutants grown aerobically in copper-deficient media is attributable to the defect in Cu,Zn superoxide dismutase activity. C1 NICHHD, CELL BIOL & METAB BRANCH, BETHESDA, MD 20892 USA. NR 44 TC 310 Z9 316 U1 1 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 14 PY 1994 VL 269 IS 41 BP 25660 EP 25667 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ491 UT WOS:A1994PQ49100066 PM 7929270 ER PT J AU YE, JP GHOSH, P CIPPITELLI, M SUBLESKI, J HARDY, KJ ORTALDO, JR YOUNG, HA AF YE, JP GHOSH, P CIPPITELLI, M SUBLESKI, J HARDY, KJ ORTALDO, JR YOUNG, HA TI CHARACTERIZATION OF A SILENCER REGULATORY ELEMENT IN THE HUMAN INTERFERON-GAMMA PROMOTER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MURINE LEUKEMIA-VIRUS; TRANSCRIPTION FACTOR; NEGATIVE CONTROL; DNA ELEMENT; C-MYC; ENHANCER; BINDS; EXPRESSION; PROTEIN; SITE AB Previous analysis of the human interferon-gamma (IFN-gamma promoter indicated that the region of DNA from -251 to -215 (designated here as BE (binding element)) possessed silencer activity, as deletion of this region caused an increase in promoter activity. Based on this finding, we have conducted a series of experiments to characterize BE function and analyze the binding proteins which interact with this region. Transient transfection assays in the Jurkat T cell line revealed that the BE region possesses silencer activity, which is orientation-dependent when reinserted 5' to the IFN-gamma core promoter. However, when the BE region was inserted in front of a heterologous promoter (thymidine kinase (TK)), a mild enhancer activity was observed. Utilizing the electrophoretic mobility shift assay, we have identified two major DNA-protein complexes (designated as S and E complexes) which interact with this region. Mutational analysis indicated that the silencer activity observed with the IFN-gamma promoter correlated with the S complex and the enhancer activity correlated with the E complex. Preliminary characterization of these two DNA-protein complexes has demonstrated the presence of multiple proteins in each complex. We have found that the S protein complex has a recognition sequence similar to the nuclear factor AP2, and we have identified the nuclear factor Yin-Yang 1 (YY1) as one of the proteins in the E complex. C1 NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. UNIV MISSISSIPPI,MED CTR,DEPT MED,JACKSON,MS 39216. NR 36 TC 65 Z9 66 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 OCT 14 PY 1994 VL 269 IS 41 BP 25728 EP 25734 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ491 UT WOS:A1994PQ49100074 PM 7929277 ER PT J AU JOE, YA PARK, MH AF JOE, YA PARK, MH TI STRUCTURAL FEATURES OF THE EIF-5A PRECURSOR REQUIRED FOR POSTTRANSLATIONAL SYNTHESIS OF DEOXYHYPUSINE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSLATION INITIATION-FACTOR; HYPUSINE-CONTAINING PROTEIN; SACCHAROMYCES-CEREVISIAE; SEQUENCE DETERMINATION; FACTOR 4D; SPERMIDINE; CDNA; IDENTIFICATION; PURIFICATION; CLEAVAGE AB Eukaryotic translation initiation factor 5A (eIF-5A, older nomenclature, eIF-4D) is a highly conserved protein that contains the unusual amino acid hypusine ((epsilon)-(4-amino-2-hydroxybutyl)lysine). The biosynthesis of hypusine occurs posttranslationally in only this protein by modification of a single lysine residue (Lys(50) in the human eIF-5A precursor). The basis for the specificity of this modification with respect to the substrate protein was investigated using fragments of eIF-5A precursor protein, each containing this lysine residue, as substrates for deoxyhypusine synthase, the first enzyme in hypusine synthesis. Proteolytic fragments (5-6 kDa) of ec-eIF-5A (the precursor form of eIF-5A produced in Escherichia coli by expression of the human eIF-5A cDNA) generated by specific cleavage by endoproteinases Arg-C, Asp-N, or Glu-C, did not act as substrates for deoxyhypusine synthesis. A series of truncated forms of the eIF-5A precursor protein generated by expression in E. coli of recombinant deletion constructs from the human eIF-5A cDNA were tested. Truncation of up to 9 amino acid residues (Met(1)-Thr(9)) from the NH, terminus or 64 amino acid residues (Leu(91)-Lys(154)) from the COOH terminus did not significantly decrease the substrate reactivity, but removal of an additional 10 amino acids from either side did, Deletion of 34 amino acid residues (Met(1)-Lys(34)) from the NH2 terminus or of 84 amino acid residues (Asp(71)-Lys(154)) from the carboxyl terminus caused complete loss of substrate property. The results obtained thus far define the minimum domain of the eIF-5A precursor protein required for enzymatic deoxyhypusine synthesis as Phe(30)-Asp(80), which corresponds to a region of high amino acid conservation in this protein throughout the eukaryotic kingdom. C1 NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. NR 24 TC 36 Z9 37 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 14 PY 1994 VL 269 IS 41 BP 25916 EP 25921 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ491 UT WOS:A1994PQ49100099 PM 7929297 ER PT J AU WANG, WL DARWIN, WD CONE, EJ AF WANG, WL DARWIN, WD CONE, EJ TI SIMULTANEOUS ASSAY OF COCAINE, HEROIN AND METABOLITES IN HAIR, PLASMA, SALIVA AND URINE BY GAS-CHROMATOGRAPHY MASS-SPECTROMETRY SO JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS LA English DT Article ID TESTING HUMAN-HAIR; DRUGS; ABUSE; IDENTIFICATION; MORPHINE AB As part of an ongoing research program on the development of drug detection methodology, we developed an assay for the simultaneous measurement of cocaine, heroin and metabolites in plasma, saliva, urine and hair by solid-phase extraction (SPE) and gas chromatography-mass spectrometry (GC-MS). The analytes that could be measured by this assay were the following: anhydroecgonine methyl ester; ecgonine methyl ester; ecgonine ethyl ester; cocaine; cocaethylene; benzoylecgonine; cocaethylene; norcocaethylene; benzoylnorecgonine; codeine; morphine; norcodeine; 6-acetylmorphine; normorphine; and heroin. Liquid specimens were diluted, filtered and then extracted by SPE. Additional handling steps were necessary for the analysis of hair samples. An initial wash procedure was utilized to remove surface contaminants. Washed hair samples were extracted with methanol overnight at 40 degrees C. Both wash and extract fractions were collected, evaporated and purified by SPE. All extracts were evaporated, derivatized with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) with 1% trimethylchlorosilane (TMCS) and analyzed by GC-MS. The limit of detection (LOD) for cocaine, heroin and metabolites in biological specimens was approximately 1 ng/ml with the exception of norcodeine, normorphine and benzoylnorecgonine (LOD = 5 ng/ml). The LOD for cocaine, heroin and metabolites in hair was approximately 0.1 ng/mg of hair with the exception of norcodeine (LOD = 0.3 ng/mg) and normorphine and benzoylnorecgonine (LOD = 0.5 ng/mg). Coefficients of variation ranged from 3 to 26.5% in the hair assay. This assay has been successfully utilized in research on the disposition of cocaine, heroin and metabolites in hair, plasma, saliva and urine and in treatment studies. C1 NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. NR 12 TC 89 Z9 93 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B-Biomed. Appl. PD OCT 14 PY 1994 VL 660 IS 2 BP 279 EP 290 DI 10.1016/0378-4347(94)00309-2 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PN823 UT WOS:A1994PN82300008 PM 7866518 ER PT J AU FERRALA, NF GHANAYEM, BI NOMEIR, AA AF FERRALA, NF GHANAYEM, BI NOMEIR, AA TI DETERMINATION OF 1-METHOXY-2-PROPANOL AND ITS METABOLITE 1,2-PROPANEDIOL IN RAT AND MOUSE PLASMA BY GAS-CHROMATOGRAPHY SO JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS LA English DT Article ID GLYCOL MONOMETHYL ETHER; INHALATION; MICE AB A method utilizing capillary GC and flame ionization detection was developed for the simultaneous determination of 1-methoxy-2-propanol (propylene glycol monomethyl ether; PGME) and its metabolite 1,2-propanediol (propylene glycol; PG) in rat and mouse plasma. The calibration graphs for rat and mouse plasma were linear with correlation coefficients at >0.997 over the range 2-700 mu g/ml. The limit of quantification was ca. 2 mu g/ml (2 ng on-column) for both compounds in plasma of each species. The ranges of the precision and accuracy for PGME were 2.8-8.8% and 3.2-13%, respectively, and for PG were 11-26% and 10-25%, respectively. The recovery of PGME from rat and mouse plasma was ca. 73% and for PG it was ca. 65 and 31% from rat and mouse plasma, respectively. The method was used to study the oral absorption and metabolism of PGME in mice. PGME was readily absorbed and metabolized to PG following oral gavage administration at 90 mg/kg. The maximum concentrations of PGME and PG in plasma were attained at 20 and 30 min following dosing, respectively. C1 ARTHUR D LITTLE INC,CAMBRIDGE,MA 02142. NIEHS,RES TRIANGLE PK,NC 27709. FU NIEHS NIH HHS [N01-ES-65138] NR 6 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B-Biomed. Appl. PD OCT 14 PY 1994 VL 660 IS 2 BP 291 EP 296 DI 10.1016/0378-4347(94)00286-X PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PN823 UT WOS:A1994PN82300009 PM 7866519 ER PT J AU KIM, HO JI, XD SIDDIQI, SM OLAH, ME STILES, GL JACOBSON, KA AF KIM, HO JI, XD SIDDIQI, SM OLAH, ME STILES, GL JACOBSON, KA TI 2-SUBSTITUTION OF N-6-BENZYLADENOSINE-5'-URONAMIDES ENHANCES SELECTIVITY FOR A-3 ADENOSINE RECEPTORS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MOLECULAR-CLONING; ADENYLATE-CYCLASE; RAT-BRAIN; ACTIVATION; BINDING; CELLS AB Adenosine derivatives bearing an N-6-(3-iodobenzyl) group, reported to enhance the affinity of adenosine-5'-uronamide analogues as agonists at A(3) adenosine receptors (J. Med. Chem. 1994, 37, 636-646), were synthesized starting from methyl beta-D-ribofuranoside in 10 steps. Binding affinities at A(1) and A(2a) receptors in rat brain membranes and at cloned rat A(3) receptors from stably transfected CHO cells were compared. N-6-(3-Iodobenzyl)adenosine was 2-fold selective for A(3) vs A(1) or A(2a) receptors; thus it is the first monosubstituted adenosine analogue having any A(3) selectivity. The effects of 8-substitution in combination with modifications at the N-6- and 5'-positions were explored. 2-Chloro-N-6-(3-iodobenzyl)adenosine had a K-i value of 1.4 nM and moderate selectivity for A(3) receptors. 2-Chloro-N-6-( 3-iodobenzyl)adenosine-5'-N-methyluronamide, which displayed a K-i value of 0.33 nM, was selective for A(3) vs A(1) and A(2a) receptors by 2500- and 1400-fold, respectively. It was 46,000-fold selective for A(3) receptors vs the Na+-independent adenosine transporter, as indicated in displacement of [H-3]N-6-(4-nitrobenzyl)-thioinosine binding in rat brain membranes. In a functional assay in CHO cells, it inhibited adenylate cyclase via rat A(3) receptors with an IC50 Of 67 nM. 2-(Methylthio)-N-6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide and 2-(methylamino)-N-6-(3-iodobenzyl)-adenosine thyluronamide were less potent, but nearly as selective for A(3) receptors. Thus, 2-substitution (both small and sterically bulky) is well-tolerated at A(3) receptors, and its A(3) affinity-enhancing effects are additive with effects of uronamides at the 5'-position and a 3-iodobenzyl group at the NG-position. C1 NIDDK,BIOORGAN CHEM LAB,MOLEC RECOGNIT SECT,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT PHARMACOL,DURHAM,NC 27710. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z99 DK999999, Z01 DK031117-20] NR 28 TC 173 Z9 173 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 OCT 14 PY 1994 VL 37 IS 21 BP 3614 EP 3621 DI 10.1021/jm00047a018 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA PM606 UT WOS:A1994PM60600018 PM 7932588 ER PT J AU JONES, LS GROOMS, SY SALVADORI, S LAZARUS, LH AF JONES, LS GROOMS, SY SALVADORI, S LAZARUS, LH TI DERMORPHIN-INDUCED HYPEREXCITABILITY IN HIPPOCAMPAL CA3 AND CA1 IN-VITRO SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE MU-OPIOID RECEPTOR; HIPPOCAMPAL SLICE; NALOXONE; PROCONVULSANT; BURSTING ID LONG-TERM POTENTIATION; MU-OPIOID RECEPTOR; AMPHIBIAN SKIN; BIOLOGICAL-ACTIVITIES; NALOXONE BLOCKS; RAT HIPPOCAMPUS; LOCUS-CERULEUS; BRAIN-SLICES; FROG-SKIN; PEPTIDES AB Dermorphin, a specific mu(1)-opioid receptor agonist, has been studied for its effects on the physiology of the rat hippocampal slice. Population responses in CA3 to threshold levels of stimulation from both the Schaffer collaterals and messy fibers were markedly enhanced in the presence of 50-100 nM dermorphin, while CA1 responses to threshold Schaffer collateral stimulation were less effected. Responses at higher stimulus levels than threshold were negligibly responsive to dermorphin, although at 500 nM dermorphin all responses became epileptiform and in some slices spontaneous bursting erupted. [L-Ala(2)]Dermorphin, a biologically inactive dermorphin analogue, did not increase response amplitudes nor evoke epilepsy in the slice. 5 mu M naloxone blocked the effect of dermorphin on Schaffer collateral and messy fiber-evoked responses, though less effectively in the latter case. These data provide in vitro evidence to support in vivo observations that excessive mu-opioid receptor activation can be proconvulsant in the hippocampus, but that normally the receptors may function as facilitatory modulators of responses in the threshold range. C1 UNIV FERRARA,DEPT PHARMACEUT SCI,I-44100 FERRARA,ITALY. NIEHS,PEPTIDE NEUROCHEM SECT,RES TRIANGLE PK,NC 27709. RP JONES, LS (reprint author), UNIV S CAROLINA,SCH MED,DEPT ANAT & DEV BIOL,COLUMBIA,SC 29208, USA. OI SALVADORI, Severo/0000-0002-8224-2358 FU NINDS NIH HHS [NS27903] NR 56 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD OCT 13 PY 1994 VL 264 IS 1 BP 39 EP 48 DI 10.1016/0014-2999(94)90633-5 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PM470 UT WOS:A1994PM47000006 PM 7828641 ER PT J AU RODGERS, GP WALKER, EC PODGOR, MJ AF RODGERS, GP WALKER, EC PODGOR, MJ TI MORTALITY IN SICKLE-CELL DISEASE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID HYPERTENSION RP RODGERS, GP (reprint author), NIH,BETHESDA,MD 20892, USA. NR 6 TC 3 Z9 3 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 13 PY 1994 VL 331 IS 15 BP 1022 EP 1022 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PK504 UT WOS:A1994PK50400021 PM 8084346 ER PT J AU BIESECKER, LG WILFOND, BS AF BIESECKER, LG WILFOND, BS TI GENERIC CONSENT FOR GENETIC SCREENING SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 UNIV ARIZONA,HLTH SCI CTR,TUCSON,AZ 85721. RP BIESECKER, LG (reprint author), NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892, USA. NR 3 TC 2 Z9 2 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 13 PY 1994 VL 331 IS 15 BP 1024 EP 1024 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PK504 UT WOS:A1994PK50400029 PM 8084349 ER PT J AU GRANOFF, DM HOLMES, SJ BEISHE, RB OSTERHOLM, MT MCHUGH, JE ANDERSON, EL AF GRANOFF, DM HOLMES, SJ BEISHE, RB OSTERHOLM, MT MCHUGH, JE ANDERSON, EL TI EFFECT OF CARRIER PROTEIN PRIMING ON ANTIBODY-RESPONSES TO HAEMOPHILUS-INFLUENZAE TYPE-B CONJUGATE VACCINES IN INFANTS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID INDUCED EPITOPIC SUPPRESSION; CAPSULAR POLYSACCHARIDE; IMMUNOGENICITY; IMMUNIZATION; DIPHTHERIA; IGG; INDUCTION; DISEASE AB Objective.-To assess the effect of priming with diphtheria and tetanus toroid vaccine (DT) at 1 month of age on the anticapsular polyribosylribitol phosphate (PRP) antibody responses of infants vaccinated with Haemophilus influenzae type b polysaccharide-tetanus toroid conjugate (PRP-T) or PRP oligosaccharide-cross-reactive mutant diphtheria toxin conjugate (HbOC). Design.-Randomized controlled trial with serum samples assayed blindly. Participants and Setting.-Healthy infants enrolled in private pediatric practices; 94 (91%) of 103 infants had prevaccination and postvaccination serum samples available for analysis. Interventions.-Two groups received DT vaccination at 1 month of age and subsequent injections of PRP-T or HbOC conjugate vaccines at 2, 4, and 6 months of age. The control groups were not vaccinated with DT but received PRP-T or HbOC at the same ages as the carrier-primed groups. Infants in all groups were given a booster injection of unconjugated PRP at 12 months of age to assess induction of immunologic memory. Main Outcome Measure.-Concentrations of serum antibody to PRP. Main Results.-The DT-primed infants given PRP-T had twofold to threefold higher geometric mean anti-PRP antibody responses after one (P less than or equal to.01), two (P less than or equal to.01), or three (P=.06) doses of conjugate vaccine than the infants of the unprimed group. The primed infants also had threefold higher memory antibody responses to the booster PRP injection given at 12 months of age (concentration of 24.4 vs 8.4 mu g/mL in infants not primed with DT; P<.01). The DT-primed infants given HbOC had twofold to threefold higher antibody responses after one (P=.07) or two (P<.01) doses of conjugate vaccine than the unprimed HbOC group, but there were no significant differences after the third dose of conjugate vaccine or after the PRP booster injection. Conclusions.-Vaccination with DT at 1 month of age increases the magnitude of the anti-PRP antibody responses to conjugate vaccination. With HbOC, the effect of carrier priming was present for up to 6 months of age, whereas in infants vaccinated with PRP-T, enhanced immunity was present for at least 12 months. C1 WASHINGTON UNIV,SCH MED,EDWARD MALLINCKRODT DEPT PEDIAT,DIV INFECT DIS,ST LOUIS,MO 63110. CTR DIS CONTROL & PREVENT,NATL IMMUNIZATION PROGRAM,ATLANTA,GA 30333. ST LOUIS UNIV,SCH MED,DEPT PEDIAT,NIAID,VACCINE EVALUAT UNIT,ST LOUIS,MO 63104. ST LOUIS UNIV,SCH MED,DEPT MED,ST LOUIS,MO 63104. MINNESOTA DEPT HLTH,ACUTE DIS EPIDEMIOL SECT,MINNEAPOLIS,MN. CHILDRENS CLIN,WAYATA,MN. CHIRON CORP,BIOCENE CLIN RES,EMERYVILLE,CA 94608. RP GRANOFF, DM (reprint author), CHILDRENS HOSP OAKLAND,RES INST,747 52ND ST,OAKLAND,CA 94609, USA. FU NIAID NIH HHS [AI 17962, F33 AI 08851, AI 21842] NR 35 TC 52 Z9 54 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 12 PY 1994 VL 272 IS 14 BP 1116 EP 1121 DI 10.1001/jama.272.14.1116 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA PK124 UT WOS:A1994PK12400031 PM 7933324 ER PT J AU QIAN, SW BURMESTER, JK SUN, PD HUANG, A OHLSEN, DJ SUARDET, L FLANDERS, KC DAVIES, D ROBERTS, AB SPORN, MB AF QIAN, SW BURMESTER, JK SUN, PD HUANG, A OHLSEN, DJ SUARDET, L FLANDERS, KC DAVIES, D ROBERTS, AB SPORN, MB TI CHARACTERIZATION OF MUTATED TRANSFORMING GROWTH FACTOR-BETA-S WHICH POSSESS UNIQUE BIOLOGICAL PROPERTIES SO BIOCHEMISTRY LA English DT Article ID TGF-BETA RECEPTOR; II RECEPTOR; CELL-LINES; MEMBRANE PROTEOGLYCAN; ENDOTHELIAL-CELLS; CRYSTAL-STRUCTURE; FACTOR-BETA-1; PROTEIN; CLONING; GROWTH-FACTOR-BETA-2 AB Transforming growth factor-beta (TGF-beta) is a potent regulator of cell growth and differentiation. On the basis of the crystal structure df TGF-beta 2, we have designed and synthesized two mutant TGF-beta s, TGF-beta 1(71 Trp) and TGF-beta 1(Delta 69-73). Although both of these molecules inhibited the growth of Mv1Lu mink lung epithelial cells and LS1034 colorectal cancer cells, which are affected equally by TGF-beta 1 and TGF-beta 2, TGF-beta 1(Delta 69-73) was much less potent than TGF-beta 1 or TGF-beta 1(71 Trp) at inhibiting the growth of LS513 colorectal cancer cells which are growth-inhibited by TGF-beta 1 but not TGF-beta 2. Both TGF-beta 1 (71 Trp) and TGF-beta 1(Delta 69-73) increased levels of mRNAs for fibronectin and plasminogen activator inhibitor with Mv1Lu cells, whereas only TGF-beta 1(71 Trp) and not TGF-beta 1(Delta 69-73) up-regulated the mRNA level of carcinoembryonic antigen in LS513 cells. The expression level of carcinoembryonic antigen mRNA in LS1034 cells was not altered by either wild-type or mutant TGF-Ps. Receptor labeling experiments demonstrated that TGF-beta 1(71 Trp) bound with high affinity to the cell-surface receptors of Mv1Lu, LS1034, and LS513 cells while TGF-beta 1(Delta 69-73) bound effectively to the receptors of Mv1Lu and LS1034 cells but much less to the receptors on LS513 cells. In contrast, binding of TGF-beta 1(71 Trp) and TGF-beta 1(Delta 69-73) to endoglin and the type II receptor of human umbilical vein endothelial cells (HUVECs) was similar to TGF-beta 1, not TGF-beta 2. These results demonstrate the feasibility of synthesizing TGF-beta mutants with unique biological properties. C1 MARSHFIELD MED RES & EDUC FDN,MARSHFIELD,WI 54449. NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. HARVARD UNIV,SCH PUBL HLTH,RADIOBIOL LAB,BOSTON,MA 02115. RP QIAN, SW (reprint author), NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892, USA. NR 42 TC 19 Z9 19 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 OCT 11 PY 1994 VL 33 IS 40 BP 12298 EP 12304 DI 10.1021/bi00206a037 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PL358 UT WOS:A1994PL35800037 PM 7918451 ER PT J AU LARIONOV, V KOUPRINA, N NIKOLAISHVILI, N RESNICK, MA AF LARIONOV, V KOUPRINA, N NIKOLAISHVILI, N RESNICK, MA TI RECOMBINATION DURING TRANSFORMATION AS A SOURCE OF CHIMERIC MAMMALIAN ARTIFICIAL CHROMOSOMES IN YEAST (YACS) SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CARRYING HUMAN DNA; SACCHAROMYCES-CEREVISIAE; HUMAN GENOME; MITOTIC RECOMBINATION; GENETIC-CONTROL; CONSTRUCTION; LIBRARY; CLONES; CLONING; SEQUENCES AB Mammalian DNAs cloned as artificial chromosomes in yeast (YACs) frequently are chimeras formed between noncontiguous DNAs. Using pairs of human and mouse YACs we examined the contribution of recombination during transformation or subsequent mitotic growth to chimeric YAC formation. The DNA from pairs of yeast strains containing homologous or heterologous YACs was transformed into a third strain under conditions typical for the development of YAC libraries. One YAC was selected and the presence of the second was then determined. Co-penetration of large molecules, as deduced from co-transformation of markers identifying the different YACs, was > 50%. In approximately half the cells receiving two homologous YACs, the YACs had undergone recombination. Co-transformation depends on recombination since it was reduced nearly 10-fold when the YACs were heterologous. While mitotic recombination between homologous YACs is nearly 100-fold higher than for yeast chromosomes, the level is still much lower than observed during transformation. To investigate the role of commonly occurring Alu repeats in chimera formation, spheroplasts were transformed with various human YACs and an unselected DNA fragment containing an Alu at one end and a telomere at the other. When unbroken YACs were used, between 1 and 6% of the selected YACs could incorporate the fragment as compared to 49% when the YACs were broken. We propose that Alu's or other commonly occurring repeats could be an important source of chimeric YACs. Since the frequency of chimeras formed between YACs or a YAC and an Alu-containing fragment was reduced when a rad52 mutant was the recipient and since intra-YAC deletions are reduced, rad52 and possibly other recombination-deficient mutants are expected to be useful for YAC library development. C1 RUSSIAN ACAD SCI, INST CYTOL, ST PETERSBURG, RUSSIA. RP NIEHS, MOLEC GENET LAB, BOX 12233, RES TRIANGLE PK, NC 27709 USA. FU NHGRI NIH HHS [1-YO2-HG-60021-01] NR 66 TC 35 Z9 36 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT 11 PY 1994 VL 22 IS 20 BP 4154 EP 4162 DI 10.1093/nar/22.20.4154 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ220 UT WOS:A1994PQ22000019 PM 7937141 ER PT J AU MUSHEGIAN, AR EDSKES, HK KOONIN, EV AF MUSHEGIAN, AR EDSKES, HK KOONIN, EV TI EUKARYOTIC RNASE-H SHARES A CONSERVED DOMAIN WITH CAULIMOVIRUS PROTEINS THAT FACILITATE TRANSLATION OF POLYCISTRONIC RNA SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CAULIFLOWER MOSAIC-VIRUS; RIBONUCLEASE-H; MESSENGER-RNA; SEQUENCES; TRANSACTIVATOR; RETROVIRUSES; EVOLUTION; GENES AB RNAse H (RNH1 protein) from the trypanosomatid Crithidia fasciculata has a functionally uncharacterized N-terminal domain dispensable for the RNAse H activity. Using computer methods for database search and multiple alignment, we show that the N-terminal domains of RNH1 and its homologue encoded by a cDNA from chicken lens are related to the conserved domain in caulimovirus ORF VI product that facilitates translation of polycistronic virus RNA in plant cells. We hypothesize that the N-terminal domain of eukaryotic RNAse H performs an as yet uncharacterized regulatory function, possibly in mRNA translation or turnover. C1 UNIV KENTUCKY,DEPT PLANT PATHOL,LEXINGTON,KY 40546. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. OI Mushegian, Arcady/0000-0002-6809-9225 NR 30 TC 18 Z9 18 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 OCT 11 PY 1994 VL 22 IS 20 BP 4163 EP 4166 DI 10.1093/nar/22.20.4163 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ220 UT WOS:A1994PQ22000020 PM 7937142 ER PT J AU LARIONOV, V GRAVES, J KOUPRINA, N RESNICK, MA AF LARIONOV, V GRAVES, J KOUPRINA, N RESNICK, MA TI THE ROLE OF RECOMBINATION AND RAD52 IN MUTATION OF CHROMOSOMAL DNA TRANSFORMED INTO YEAST SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ARTIFICIAL-CHROMOSOME; SACCHAROMYCES-CEREVISIAE; ECTOPIC RECOMBINATION; GENETIC-DIFFERENCES; MAMMALIAN-CELLS; S-CEREVISIAE; MOUSE CELLS; CONSTRUCTION; SEQUENCES; LIBRARY AB While transformation is a prominent tool for genetic analysis and genome manipulation in many organisms, transforming DNA has often been found to be unstable relative to established molecules. We determined the potential for transformation-associated mutations in a 360 kb yeast chromosome III composed primarily of unique DNA. Wild-type and rad52 Saccharomyces cerevisiae strains were transformed with either a homologous chromosome III or a diverged chromosome III from S.carlsbergensis. The host strain chromosome III had a conditional centromere allowing it to be lost on galactose medium so that recessive mutations in the transformed chromosome could be identified. Following transformation of a RAD(+) strain with the homologous chromosome, there were frequent changes in the incoming chromosome, including large deletions and mutations that do not lead to detectable changes in chromosome size. Based on results with the diverged chromosome, interchromosomal recombinational interactions were the source of many of the changes. Even though rad52 exhibits elevated mitotic mutation rates, the percentage of transformed diverged chromosomes incapable of substituting for the resident chromosome was not increased in rad52 compared to the wild-type strain, indicating that the mutator phenotype does not extend to transforming chromosomal DNA. Based on these results and our previous observation that the incidence of large mutations is reduced during the cloning of mammalian DNA into a rad52 as compared to a RAD(+) strain, a rad52 host is well-suited for cloning DNA segments in which gene function must be maintained. RP LARIONOV, V (reprint author), NIEHS,MOLEC GENET LAB,BOX 12233,RES TRIANGLE PK,NC 27709, USA. FU NHGRI NIH HHS [1-YO2-HG-60021-01] NR 61 TC 6 Z9 6 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT 11 PY 1994 VL 22 IS 20 BP 4234 EP 4241 DI 10.1093/nar/22.20.4234 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ220 UT WOS:A1994PQ22000031 PM 7937151 ER PT J AU CALLOW, MJ FERRIN, LJ RUBIN, EM AF CALLOW, MJ FERRIN, LJ RUBIN, EM TI SINGLE-BASE, SITE-DIRECTED MUTAGENESIS OF A 90-KILOBASE-PAIR P1-CLONE SO NUCLEIC ACIDS RESEARCH LA English DT Note ID PHENOTYPIC SELECTION; DNA C1 NIDDKD,GENET & BIOCHEM BRANCH,BETHESDA,MD 20892. RP CALLOW, MJ (reprint author), UNIV CALIF BERKELEY,LAWRENCE BERKELEY LAB,DIV LIFE SCI,BERKELEY,CA 94720, USA. FU NHLBI NIH HHS [HL-20985, HL-5P60, HL 18574] NR 5 TC 8 Z9 8 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 OCT 11 PY 1994 VL 22 IS 20 BP 4348 EP 4349 DI 10.1093/nar/22.20.4348 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ220 UT WOS:A1994PQ22000048 PM 7937166 ER PT J AU HERMAN, JG LATIF, F WENG, YK LERMAN, MI ZBAR, B LIU, S SAMID, D DUAN, DSR GNARRA, JR LINEHAN, WM BAYLIN, SB AF HERMAN, JG LATIF, F WENG, YK LERMAN, MI ZBAR, B LIU, S SAMID, D DUAN, DSR GNARRA, JR LINEHAN, WM BAYLIN, SB TI SILENCING OF THE VHL TUMOR-SUPPRESSOR GENE BY DNA METHYLATION IN RENAL-CARCINOMA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CELL CARCINOMA; ALLELIC LOSS; SHORT ARM; DENOVO METHYLATION; HUMAN NEOPLASIA; COLON-CANCER; CPG ISLANDS; HYPERMETHYLATION; PROGRESSION; LINES AB Mutational inactivation and allelic loss of the von Hippel-Lindan (VHL) gene appear to be causal events for the majority of spontaneous clear-cell renal carcinomas. We now show that hypermethylation of a normally unmethylated CPG island in the 5' region provides another potentially important mechanism for inactivation of the VHL gene in a significant portion of these cancers. This hypermethylation was found in 5 of 26 (19%) tumors examined. Four of these had lost one copy of VHL while one retained two heavily methylated alleles. Four of the tumors with VHL hypermethylation had no detectable mutations, whereas one had a missense mutation in addition to hypermethylation of the single retained allele. As would be predicted for the consequence of methylation in this 5' CpG island, none of the 5 tumors expressed the VHL gene. In contrast, normal kidney and all tumors examined with inactivating VHL gene mutations but no CpG island methylation had expression. In a renal cell culture line, treatment with 5-aza-2'-deoxycytidine resulted in reexpression of the VHL gene. These findings suggest that aberrant methylation of CpG islands may participate in the tumor-suppressor gene inactivations which initiate or cause progression of common human cancers. C1 JOHNS HOPKINS MED INST,DEPT MED,BALTIMORE,MD 21231. NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21702. NCI,SURG BRANCH,UROL ONCOL SECT,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. RP HERMAN, JG (reprint author), JOHNS HOPKINS MED INST,CTR ONCOL,BALTIMORE,MD 21231, USA. FU NCI NIH HHS [CA 43318] NR 36 TC 1161 Z9 1203 U1 3 U2 25 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 11 PY 1994 VL 91 IS 21 BP 9700 EP 9704 DI 10.1073/pnas.91.21.9700 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PM138 UT WOS:A1994PM13800008 PM 7937876 ER PT J AU LEE, MS CRAIGIE, R AF LEE, MS CRAIGIE, R TI PROTECTION OF RETROVIRAL DNA FROM AUTOINTEGRATION - INVOLVEMENT OF A CELLULAR FACTOR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MURINE LEUKEMIA-VIRUS; INTEGRATION INVITRO; POL GENE; PROTEIN; INFECTION; CLEAVAGE; PRODUCT; TYPE-1 AB An essential step in the retrovirus life cycle is integration of a DNA copy of the viral genome into a host chromosome. After reverse transcription, there can be a delay of many hours before the viral DNA is integrated. It is important for the retrovirus to ensure that the viral DNA does not integrate into itself during this period; such autointegration is a suicidal process that would result in destruction of the viral genome. Understanding of the mechanism that blocks autointegration of the viral DNA may lead to insights into how to inhibit viral replication by inducing the viral DNA to autointegrate. Evidence is presented in this report that viral nucleoprotein complexes isolated from cells infected with Moloney murine leukemia virus exhibit a barrier to autointegration. The barrier can be disrupted by high salt treatment and, subsequently, restored by addition of factors provided by a host cell extract. Our data indicate an involvement of host machinery in protecting retroviral DNA from autointegration. RP LEE, MS (reprint author), NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 21 TC 107 Z9 112 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 11 PY 1994 VL 91 IS 21 BP 9823 EP 9827 DI 10.1073/pnas.91.21.9823 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PM138 UT WOS:A1994PM13800033 PM 7937898 ER PT J AU YAMANAKA, S JOHNSON, MD GRINBERG, A WESTPHAL, H CRAWLEY, JN TANIIKE, M SUZUKI, K PROIA, RL AF YAMANAKA, S JOHNSON, MD GRINBERG, A WESTPHAL, H CRAWLEY, JN TANIIKE, M SUZUKI, K PROIA, RL TI TARGETED DISRUPTION OF THE HEXA GENE RESULTS IN MICE WITH BIOCHEMICAL AND PATHOLOGICAL FEATURES OF TAY-SACHS-DISEASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ANIMAL MODEL; G(M2) GANGLIOSIDOSIS; HOMOLOGOUS RECOMBINATION; LYSOSOMAL STORAGE DISEASE ID HEXOSAMINIDASE-A; CATS AB Tay-Sachs disease, the prototype of the G(M2) gangliosidoses, is a catastrophic neurodegenerative disorder of infancy. The disease is caused by mutations in the HEXA gene resulting in an absence of the lysosomal enzyme, beta-hexosaminidase A. As a consequence of the enzyme deficiency, G(M2) ganglioside accumulates progressively, beginning early in fetal life, to excessive amounts in the central nervous system. Rapid mental and motor deterioration starting in the first year of life leads to death by 2-4 years of age. Through the targeted disruption of the mouse Hexa gene in embryonic stem cells, we have produced mice with biochemical and neuropathologic features of Tay-Sachs disease. The mutant mice displayed <1% of normal beta-hexosaminidase A activity and accumulated G(M2) ganglioside in their central nervous system in an age-dependent manner. The accumulated ganglioside was stored in neurons as membranous cytoplasmic bodies characteristically found in the neurons of Tay-Sachs disease patients. At 3-5 months of age, the mutant mice showed no apparent defects in motor or memory function. These beta-hexosaminidase A deficient mice should be useful for devising strategies to introduce functional enzyme and genes into the central nervous system. This model may also be valuable for studying the biochemical and pathologic changes occurring during the course of the disease. C1 NIDDKD,GENET & BIOCHEM BRANCH,BIOCHEM GENET SECT,BETHESDA,MD 20892. NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892. NIMH,EXPTL THERAPEUT BRANCH,BEHAV NEUROPHARMACOL SECT,BETHESDA,MD 20892. UNIV N CAROLINA,DEPT PATHOL,CHAPEL HILL,NC 27599. RI Proia, Richard/A-7908-2012 FU NICHD NIH HHS [HD03110]; NINDS NIH HHS [NS-24453] NR 22 TC 128 Z9 132 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 11 PY 1994 VL 91 IS 21 BP 9975 EP 9979 DI 10.1073/pnas.91.21.9975 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PM138 UT WOS:A1994PM13800064 PM 7937929 ER PT J AU LIN, D FISCELLA, M OCONNOR, PM JACKMAN, J CHEN, M LUO, LL SALA, A TRAVALI, S APPELLA, E MERCER, WE AF LIN, D FISCELLA, M OCONNOR, PM JACKMAN, J CHEN, M LUO, LL SALA, A TRAVALI, S APPELLA, E MERCER, WE TI CONSTITUTIVE EXPRESSION OF B-MYB CAN BYPASS P53-INDUCED WAF1/CIP1-MEDIATED G(1) ARREST SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ONCOGENE; SUPPRESSOR GENE; CELL CYCLE ID TUMOR SUPPRESSOR PROTEIN; CELL-CYCLE CHECKPOINT; WILD-TYPE P53; C-MYB; HEMATOPOIETIC-CELLS; GENE; PROLIFERATION; FIBROBLASTS; ACTIVATION; KINASES AB Overexpression of wild-type p53 protein has been shown to induce arrest ih the G(1) stage of the cell cycle and to transactivate expression of the gene that encodes the 21-kDa Waf1/Cip1 protein, a potent inhibitor of cyclin-dependent kinase activity, p53-dependent G(1) arrest is accompanied by decreased expression of the B-myb gene, a relative of the c-myb cellular oncogene. In this study we show that B-myb expression is required for cells to progress from G(1) into S phase and that high levels of ectopic B-myb expression uncoupled from cell cycle regulation rescues cells from p53-induced G(1) arrest even in the presence of Waf1/Cip1 transactivation and inhibition of cyclin E/Cdk2 kinase activity. Cotransfection experiments with p53 expression plasmids and expression plasmids encoding in-frame deletion mutations in B-myb coding sequences indicate that the DNA-binding domain of the B-myb protein is required for this activity. These results provide evidence of a bypass of p53-induced Waf1/Cip1-mediated cell cycle regulatory pathways by a member of the myb oncogene family. C1 THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19170. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT BIOCHEM & MOLEC BIOL,PHILADELPHIA,PA 19170. NCI,CELL BIOL LAB,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RI sala, arturo/C-4959-2008 FU NCI NIH HHS [CA54140, CA55541] NR 40 TC 112 Z9 112 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 11 PY 1994 VL 91 IS 21 BP 10079 EP 10083 DI 10.1073/pnas.91.21.10079 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PM138 UT WOS:A1994PM13800085 PM 7937841 ER PT J AU MILLER, JL DONAHUE, RE SELLERS, SE SAMULSKI, RJ YOUNG, NS NIENHUIS, AW AF MILLER, JL DONAHUE, RE SELLERS, SE SAMULSKI, RJ YOUNG, NS NIENHUIS, AW TI RECOMBINANT ADENOASSOCIATED VIRUS (RAAV)-MEDIATED EXPRESSION OF A HUMAN GAMMA-GLOBIN GENE IN HUMAN PROGENITOR-DERIVED ERYTHROID-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HEMATOPOIETIC STEM-CELLS; TRANSMEMBRANE CONDUCTANCE REGULATOR; MURINE ERYTHROLEUKEMIA-CELLS; RETROVIRAL-MEDIATED TRANSFER; IN-VIVO EXPRESSION; ADENOASSOCIATED VIRUS; PERIPHERAL-BLOOD; MAMMALIAN-CELLS; CONTROL REGION; VECTOR AB Effective gene therapy for the severe hemoglobin (Hb) disorders, sickle-cell anemia and thalassemia, will require an efficient method to transfer, integrate, and express a globin gene in primary erythroid cells. To evaluate recombinant adeno-associated virus (rAAV) for this purpose, we constructed a rAAV vector encoding a human gamma-globin gene (pJM24/vHS432(A) gamma*). Its 4725-nucleotide genome consists of two 180-bp AAV inverted terminal repeats flanking the core elements of hypersensitive sites 2, 3, and 4 from the locus control region of the beta-globin gene cluster, linked to a mutationally marked (A) gamma-globin gene ((A) gamma*) containing native promoter and RNA processing signals. CD34(+) human hematopoietic cells were exposed to rAAV particles at a multiplicity of infection of 500-1000 and cultured in semisolid medium containing several cytokines. A reverse transcriptase polymerase chain reaction assay distinguished mRNA signals derived from transduced and endogenous human gamma-globin genes. Twenty to 40% of human erythroid burst-forming unit-derived colonies expressed the rAAV-transduced (A) gamma*-globin gene at levels 4-71% that of the endogenous gamma-globin genes. The HbF content of pooled control colonies was 26%, whereas HbF was 40% of the total in pooled colonies derived from rAAV transduced progenitors. These data establish that rAAV containing elements from the locus control region linked to a gamma-globin gene are capable of transferring and expressing that gene in primary human hematopoietic cells resulting in a substantial increase in HbF content. C1 ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38101 USA. NHLBI, BETHESDA, MD 20892 USA. UNIV N CAROLINA, CHAPEL HILL, NC 27599 USA. FU NHLBI NIH HHS [HL 48347-03] NR 38 TC 95 Z9 98 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 OCT 11 PY 1994 VL 91 IS 21 BP 10183 EP 10187 DI 10.1073/pnas.91.21.10183 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PM138 UT WOS:A1994PM13800106 PM 7524085 ER PT J AU TSAREV, SA TSAREVA, TS EMERSON, SU GOVINDARAJAN, S SHAPIRO, M GERIN, JL PURCELL, RH AF TSAREV, SA TSAREVA, TS EMERSON, SU GOVINDARAJAN, S SHAPIRO, M GERIN, JL PURCELL, RH TI SUCCESSFUL PASSIVE AND ACTIVE IMMUNIZATION OF CYNOMOLGUS MONKEYS AGAINST HEPATITIS-E SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NON-B HEPATITIS; E VIRUS HEV; NON-A; EPIDEMIC; IMMUNOPROPHYLAXIS; ANTIBODY; VACCINE AB Virtually full protection against hepatitis E and partial or complete protection against infection with hepatitis E virus (HEV) were achieved in passively or actively immunized cynomolgus monkeys. Hepatitis, viremia, and shedding of the virus in feces were detected in all nonimmunized animals that were challenged with HEV. HEV titers detected by reverse transcriptase PCR were higher in feces than in serum of nonimmunized animals. Anti-HEV antibody titers at the time of challenge ranged between 1:40 acid 1:200 in animals passively immunized with convalescent plasma from a cynomolgus monkey previously infected with HEV and between 1:100 and 1:10,000 in animals actively immunized with a recombinant 55-kDa open reading frame 2 protein. The estimated 50% protective titer of passively acquired anti-HEV antibodies was 1:40. Although only one of four passively immunized animals showed histopathologic evidence of hepatitis, all four were infected after challenge; however, the titers of HEV in serum and feces were lower in the passively immunized animals than in the nonimmunized group. The actively immunized animals developed neither hepatitis nor viremia when challenged with HEV and virus was either not detected or was present in low titer in feces. The protective response was a function of the ELISA anti-HEV antibody titer at the time of challenge and the immunization schedule. C1 UNIV SO CALIF,RANCHO LOS AMIGOS HOSP,PATHOL & CLIN LABS,DOWNEY,CA 90242. BIOQUAL INC,ROCKVILLE,MD 20850. GEORGETOWN UNIV,SCH MED,DIV MOLEC VIROL & IMMUNOL,ROCKVILLE,MD 20852. RP TSAREV, SA (reprint author), NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BLDG 7,ROOM 200,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [N01-AI-05069, N01-AO-45180] NR 21 TC 129 Z9 143 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 11 PY 1994 VL 91 IS 21 BP 10198 EP 10202 DI 10.1073/pnas.91.21.10198 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PM138 UT WOS:A1994PM13800109 PM 7937861 ER PT J AU APPLEGATE, WB PRESSEL, S WITTES, J LUHR, J SHEKELLE, RB CAMEL, GH GREENLICK, MR HADLEY, E MOYE, L PERRY, HM SCHRON, E WEGENER, V AF APPLEGATE, WB PRESSEL, S WITTES, J LUHR, J SHEKELLE, RB CAMEL, GH GREENLICK, MR HADLEY, E MOYE, L PERRY, HM SCHRON, E WEGENER, V TI IMPACT OF THE TREATMENT OF ISOLATED SYSTOLIC HYPERTENSION ON BEHAVIORAL VARIABLES - RESULTS FROM THE SYSTOLIC HYPERTENSION IN THE ELDERLY PROGRAM SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID BLOOD-PRESSURE; CLINICAL-TRIALS; BETA-BLOCKERS; QUALITY; LIFE AB Background: Little information has been published on the impact of antihypertensive medications on quality of life in older persons. Particular concern has existed that lowering systolic blood pressure in older persons might have adverse consequences on cognition, mood, or leisure activities. Methods: A multicenter double-blind randomized controlled trial was conducted over an average of 5 years' followup involving 16 academic clinical trial clinics. Participants consisted of 4736 persons (1.06%) selected from 447 921 screenees aged 60 years and older. Systolic blood pressure at baseline ranged from 160 to 219 mm Hg, while diastolic blood pressure was less than 90 mm Hg. Participants were randomized to active antihypertensive drug therapy or matching placebo. Active treatment consisted of 12.5 to 25 mg of chlorthalidone for step 1, while step 2 consisted of 25 to 50 mg of atenolol. If atenolol was contraindicated, 0.05 to 0.10 mg of reserpine could be used for the second-step drug. The impact of drug treatment on measures of cognitive, emotional, and physical function and leisure activities was assessed. Results: Our analyses demonstrate that active treatment of isolated systolic hypertension in the Systolic Hypertension in the Elderly Program cohort had no measured negative effects and, for some measures, a slight positive effect on cognitive, physical, and leisure function. The positive findings in favor of the treatment group were small. There was no effect on measures related to emotional state. Measures of cognitive and emotional function were stable in both groups for the duration of the study. Both treatment groups showed a modest trend toward deterioration of some measures of physical and leisure function over the study period. Conclusions: The overall study cohort exhibited decline over time in activities of daily living, particularly the more strenuous ones, and some decline in certain leisure activities. However, mood, cognitive function, basic self-care, and moderate leisure activity were remarkably stable for both the active and the placebo groups throughout the entire study. Results of this study support the inference that medical treatment of isolated systolic hypertension does not cause deterioration in measures of cognition, emotional state, physical function, or leisure activities. C1 UNIV TENNESSEE,MEMPHIS,TN. UNIV TEXAS,HLTH SCI CTR,SCH PUBL HLTH,HOUSTON,TX. STAT COLLABORAT,WASHINGTON,DC. HOLLISWOOD HOSP,HOLLISWOOD,NY. WASHINGTON UNIV,SCH MED,ST LOUIS,MO. KAISER PERMANENTE CTR HLTH RES,PORTLAND,OR. NIA,BETHESDA,MD. NHLBI,BETHESDA,MD. NR 30 TC 168 Z9 169 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT 10 PY 1994 VL 154 IS 19 BP 2154 EP 2160 DI 10.1001/archinte.154.19.2154 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA PK696 UT WOS:A1994PK69600004 PM 7944835 ER PT J AU KUO, H GRANT, S MUTH, N HENGEMIHLE, J INGRAM, DK AF KUO, H GRANT, S MUTH, N HENGEMIHLE, J INGRAM, DK TI THE CORRELATION BETWEEN NEURON COUNTS AND OPTICAL-DENSITY OF NADPH-DIAPHORASE HISTOCHEMISTRY IN THE RAT STRIATUM - A QUANTITATIVE STUDY SO BRAIN RESEARCH LA English DT Article DE NADPH-DIAPHORASE; NITRIC OXIDE SYNTHASE; ENZYME HISTOCHEMISTRY ID NITRIC-OXIDE SYNTHASE; POLYPEPTIDE (APP)-LIKE IMMUNOREACTIVITIES; HUNTINGTONS-DISEASE; ALZHEIMERS-DISEASE; NEUROPEPTIDE-Y; SOMATOSTATIN; MARKER; BRAIN AB NADPH diaphorase (NADPH-d) histochemistry is a useful technique for examining select neuronal populations in both experimental studies and human neuropathology and also provides a simple method to localize nitric oxide synthase in the central nervous system. However, no established method exists for detecting quantitative changes of NADPH-d histochemistry under different experimental conditions. To develop a quantitative procedure, we systematically examined the properties of NADPH-d histochemistry and then investigated the correlation between the number of NADPH-d positive cells and the optical density of NADPH-d histochemistry in the rat striatum. NADPH-d activity was sensitive to specific experimental conditions, such as incubation time, fixation, and high temperature. In the striatum NADPH-d activity of neuropil was more sensitive to these conditions than were the somata. The different staining patterns of NADPH-d between the neuropil of the striatum and white matter, such as the optic tract suggest neuropil staining in the striatum is not just unspecific background staining. Increasing incubation time only increased the optical density of NADPH-d staining, in contrast, the number of NADPH-d positive cells counted was relatively consistent across incubation times. Therefore, little correlation existed between the optical density and cell number. These results indicate that when using NADPH-d histochemistry, the number of NADPH-d positive neurons is independent of the optical density of the staining, and these two parameters should be considered and treated separately when conducting quantitative analysis related to an experimental treatment. C1 NIA,GERONTOL RES CTR,NATHAN W SHOCK LABS,MOLEC PHYSIOL & GENET SECT,BALTIMORE,MD 21224. NIH,ARC,NEUROIMAGING & DRUG ACT SECT,BALTIMORE,MD 21224. NR 22 TC 20 Z9 20 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 OCT 10 PY 1994 VL 660 IS 1 BP 57 EP 65 DI 10.1016/0006-8993(94)90838-9 PG 9 WC Neurosciences SC Neurosciences & Neurology GA PJ969 UT WOS:A1994PJ96900007 PM 7530153 ER PT J AU MORITA, A NOMIZU, M OKITSU, M HORIE, K YOKOGOSHI, H ROLLER, PP AF MORITA, A NOMIZU, M OKITSU, M HORIE, K YOKOGOSHI, H ROLLER, PP TI D-VAL(22) CONTAINING HUMAN BIG ENDOTHELIN-1 ANALOG, [D-VAL(22)]BIG ET-1[16-38], INHIBITS THE ENDOTHELIN-CONVERTING ENZYME SO FEBS LETTERS LA English DT Article DE ENDOTHELIN-1; ENDOTHELIN CONVERTING ENZYME; D-AMINO ACID; BIG ENDOTHELIN-1 ANALOG; PROTEASE INHIBITOR; DOPAMINE ID SPLEEN FIBRINOLYTIC PROTEINASE; PHASE PEPTIDE-SYNTHESIS; CELLS; CONVERSION; ACID; PHOSPHORAMIDON; SECRETION; PLASMA; INVIVO AB Endothelin converting enzyme (ECE) is essential for generation of the biological effects of endothelin-1 (ET-1) from a precursor, big endothelin-1 (Big ET-1). We synthesized four analogs of human Big ET-1[16-38], substituted with single D-amino acids at P1, P2, P1' and P2' positions. ECE activity was determined using an ET-1 specific radioimmunoassay system. None of the D-amino acid containing Big ET-1 analogs were apparently cleaved by ECE, however, one of the synthetic peptides, [D-Val(22)]Big ET-1[16-38], strongly inhibited the ECE activity. Furthermore, when this D-Val(22) containing peptide was preadministrated to rat striatum, it was found to inhibit the dopamine release induced by Big ET-1. This result suggests that the D-Val(22) containing peptide inhibits the ECE activity in vivo. The D-Val(22) containing inhibitor offers hope of developing more potent and highly specific ECE inhibitors of therapeutic significance. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. RP MORITA, A (reprint author), UNIV SHIZUOKA,SCH FOOD & NUTR SCI,NUTR BIOCHEM LAB,52-1 YADA,SHIZUOKA 422,JAPAN. NR 29 TC 19 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD OCT 10 PY 1994 VL 353 IS 1 BP 84 EP 88 DI 10.1016/0014-5793(94)01012-9 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA PL674 UT WOS:A1994PL67400020 PM 7926029 ER PT J AU LENZ, FA GRACELY, RH ROWLAND, LH DOUGHERTY, PM AF LENZ, FA GRACELY, RH ROWLAND, LH DOUGHERTY, PM TI A POPULATION OF CELLS IN THE HUMAN THALAMIC PRINCIPAL SENSORY NUCLEUS RESPOND TO PAINFUL MECHANICAL STIMULI SO NEUROSCIENCE LETTERS LA English DT Article DE NEUROPHYSIOLOGY, NOCICEPTION; PAIN MEASUREMENT; VENTRAL POSTERIOR THALAMIC NUCLEUS; HUMAN ID SPINOTHALAMIC TRACT NEURONS; POSTERIOR LATERAL NUCLEUS; EXCITATORY AMINO-ACIDS; SOMATOSENSORY RESPONSES; AWAKE MONKEY; MICROSTIMULATION; AREA; SKIN AB A population of neurons located in the cutaneous core of the principal sensory nucleus of human thalamus (ventralis caudalis, Vc) has been identified that had their maximal response to mechanical stimuli which were perceived as painful by the patients involved. None of these cells responded to painful thermal stimuli. The graded responses of these cells to mechanical stimuli extending into the painful range suggest they both mediate acute pain in response to mechanical stimuli and participate in mechanical hyperalgesia. C1 JOHNS HOPKINS UNIV,DEPT NEUROSCI,BALTIMORE,MD. NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. RP LENZ, FA (reprint author), JOHNS HOPKINS UNIV HOSP,DEPT NEUROSURG,MEYER BLDG 7-113,600 N WOLFE ST,BALTIMORE,MD 21287, USA. OI Dougherty, Patrick/0000-0002-2177-2734 FU NINDS NIH HHS [K08-NS1384, NS28598, P01-NS32386-01] NR 26 TC 46 Z9 47 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 OCT 10 PY 1994 VL 180 IS 1 BP 46 EP 50 DI 10.1016/0304-3940(94)90910-5 PG 5 WC Neurosciences SC Neurosciences & Neurology GA PP954 UT WOS:A1994PP95400012 PM 7877759 ER PT J AU JEONG, LS NICKLAUS, MC GEORGE, C MARQUEZ, VE AF JEONG, LS NICKLAUS, MC GEORGE, C MARQUEZ, VE TI UNANTICIPATED RETENTION OF CONFIGURATION IN THE DAST FLUORINATION OF DEOXY-4'-THIOPYRIMIDINE NUCLEOSIDES WITH UP HYDROXYL-GROUPS SO TETRAHEDRON LETTERS LA English DT Article ID ANALOGS; HIV AB Fluorination of 1-(5-O-trityl-3-deoxy-4-thio-beta-D-threo-pentofuranosyl)uracil (17) and 1-(5-O-trityl-2-deoxy-4-thio-beta-D-threo-pentofuranosyl)uracil (20) with DAST proceeded with exclusive retention of configuration. The structures of the products were confirmed by X-ray analysis. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. USN,RES LAB,STRUCT MATTER LAB,WASHINGTON,DC 20375. RI Nicklaus, Marc/N-4183-2014 NR 14 TC 34 Z9 34 U1 0 U2 7 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 OCT 10 PY 1994 VL 35 IS 41 BP 7569 EP 7572 DI 10.1016/S0040-4039(00)78345-6 PG 4 WC Chemistry, Organic SC Chemistry GA PL496 UT WOS:A1994PL49600021 ER PT J AU JEONG, LS NICKLAUS, MC GEORGE, C MARQUEZ, VE AF JEONG, LS NICKLAUS, MC GEORGE, C MARQUEZ, VE TI FACILE FLUORINATION OF DEOXY-4'-THIOPYRIMIDINE NUCLEOSIDES WITH DOWN HYDROXYL-GROUPS - RETENTION OF CONFIGURATION AFTER FLUORIDE OPENING OF THE QUATERNIZED N-3-MEM ANHYDRONUCLEOSIDES SO TETRAHEDRON LETTERS LA English DT Article AB Attempted fluorination of 1-(5-O-trityl-3-deoxy-4-thio-beta-D-erythro-pentofuranosyl)-3-(2-methoxyethoxymethyl)uracil (12) and 1-(5-O-trityl-2-deoxy-4-thio-beta-D-erythro-pentofuranosyl)-3-(2-methoxyethoxymethyl) uracil (14) with diethylaminosulfur trifluoride (DAST) produced very reactive N-3-MEM-O-2,2- and N-3-MEM-O-2,3-anhydronucleoside intermediates (16) that reacted with KF to give the desired fluorinated nucleosides with retention of configuration. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. USN,RES LAB,STRUCT MATTER LAB,WASHINGTON,DC 20375. RI Nicklaus, Marc/N-4183-2014 NR 8 TC 21 Z9 21 U1 0 U2 5 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 OCT 10 PY 1994 VL 35 IS 41 BP 7573 EP 7576 DI 10.1016/S0040-4039(00)78346-8 PG 4 WC Chemistry, Organic SC Chemistry GA PL496 UT WOS:A1994PL49600022 ER PT J AU KELLY, TR GARCIA, A LANG, FR WALSH, JJ BHASKAR, KV BOYD, MR GOTZ, R KELLER, PA WALTER, R BRINGMANN, G AF KELLY, TR GARCIA, A LANG, FR WALSH, JJ BHASKAR, KV BOYD, MR GOTZ, R KELLER, PA WALTER, R BRINGMANN, G TI CONVERGENT TOTAL SYNTHESIS OF THE MICHELLAMINES SO TETRAHEDRON LETTERS LA English DT Article ID CROSS-COUPLING REACTION AB The total synthesis of both michellamine A (1a) and B (1b), by consecutive construction first of the inner (non-stereogenic) axis and subsequently the two outer (stereogenic) axes in a highly convergent manner, is described. The michellamines are of considerable interest due to their pronounced anti-HIV activity. C1 NCI,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702. UNIV WURZBURG,INST ORGAN CHEM,D-97074 WURZBURG,GERMANY. RP KELLY, TR (reprint author), BOSTON COLL,EUGENE F MERKERT CHEM CTR,DEPT CHEM,CHESTNUT HILL,MA 02167, USA. NR 19 TC 56 Z9 56 U1 1 U2 5 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 OCT 10 PY 1994 VL 35 IS 41 BP 7621 EP 7624 DI 10.1016/S0040-4039(00)78358-4 PG 4 WC Chemistry, Organic SC Chemistry GA PL496 UT WOS:A1994PL49600034 ER PT J AU GHAREHBAGHI, K SREENATH, A HAO, Z PAULL, KD SZEKERES, T COONEY, DA KROHN, K JAYARAM, HN AF GHAREHBAGHI, K SREENATH, A HAO, Z PAULL, KD SZEKERES, T COONEY, DA KROHN, K JAYARAM, HN TI COMPARISON OF BIOCHEMICAL PARAMETERS OF BENZAMIDE RIBOSIDE, A NEW INHIBITOR OF IMP DEHYDROGENASE, WITH TIAZOFURIN AND SELENAZOFURIN SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE BENZAMIDE RIBOSIDE; IMP DEHYDROGENASE INHIBITOR; SELENAZOFURIN; TIAZOFURIN; MALATE DEHYDROGENASE INHIBITOR; NAD ANALOGS ID TUMOR-CELL-LINES; K562 CELLS; 2-BETA-D-RIBOFURANOSYLSELENAZOLE-4-CARBOXAMIDE; 2-BETA-D-RIBOFURANOSYLTHIAZOLE-4-CARBOXAMIDE; CONVERSION; LEUKEMIA; ANALOGS; NAD AB The biochemical and cytotoxic activities of the IMP dehydrogenase (IMPDH) inhibitors benzamide riboside, tiazofurin, and selenazofurin were compared. These three C-nucleosides exert their cytotoxicity by forming an analogue of NAD, wherein nicotinamide is replaced by the C-nucleoside base. The antiproliferative activities of these three agents were compared in a panel of 60 human cancer cell lines. To examine the relationship of benzamide riboside and selenazofurin to tiazofurin, COMPARE computer analysis was performed, and correlation coefficients of 0.761 and 0.815 were obtained for benzamide riboside and selenazofurin, respectively. The biochemical activities of these agents were examined in human myelogenous leukemia K562 cells. Incubation of K562 cells for 4 hr with 10 mu M each of benzamide riboside. selenazofurin and tiazofurin resulted in a 49, 71, and 26% decrease in IMPDH activity with a concurrent increase in intracellular IMP pools. As a consequence of IMPDH inhibition, GTP and dGTP concentrations were curtailed. These studies demonstrated that selenazofurin was the most potent of the three agents. To compare the cellular synthesis of NAD analogues of these agents, Kj62 cells were incubated with 10 mu M each of benzamide riboside, tiazofurin and selenazofurin after prelabeling the cells with [2, 8-H-3]adenosine. The results demonstrated that benzamide riboside produced 2- and 3-fold more of NAD analogue (BAD) than tiazofurin and selenazofurin did. To elucidate the effects of the three compounds on other NAD-utilizing enzymes, the inhibitory activities of purified benzamide adenine dinucleotide (BAD), thiazole-4-carboxamide adenine dinucleotide (TAD) and selenazole-4-carboxamide adenine dinucleotide (SAD) were studied in commercially available purified preparations of lactate dehydrogenase, glutamate dehydrogenase and malate dehydrogenase. TAD and SAD did not inhibit these three dehydrogenases. Although BAD did not influence lactate and glutamate dehydrogenases, it selectively inhibited 50% of malate dehydrogenase activity at a 3.2 mu M concentration. These studies demonstrate similarities and differences in the biochemical actions of the three C-nucleosides, even though they share similar mechanisms of action. C1 INDIANA UNIV,SCH MED,EXPTL ONCOL LAB,INDIANAPOLIS,IN 46202. NCI,MED CHEM LAB,BETHESDA,MD 20892. NCI,INFORMAT TECHNOL BRANCH,BETHESDA,MD 20892. UNIV GESAMTHSCH PADERBORN,DIV ORGAN CHEM,PADERBORN,GERMANY. FU NCI NIH HHS [CA 51770] NR 23 TC 43 Z9 45 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD OCT 7 PY 1994 VL 48 IS 7 BP 1413 EP 1419 DI 10.1016/0006-2952(94)90565-7 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PM802 UT WOS:A1994PM80200014 PM 7945441 ER PT J AU DEGRAFF, W HAHN, SM MITCHELL, JB KRISHNA, MC AF DEGRAFF, W HAHN, SM MITCHELL, JB KRISHNA, MC TI FREE-RADICAL MODES OF CYTOTOXICITY OF ADRIAMYCIN(R) AND STREPTONIGRIN SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE NITROXIDES; ADRIAMYCIN; STREPTONIGRIN; EPR; SEMIQUINONE; FREE RADICALS; DNA STRAND BREAKS ID FIELD GEL-ELECTROPHORESIS; BREAST TUMOR-CELLS; DOUBLE-STRAND BREAKS; ANTI-CANCER AGENTS; HYDROGEN-PEROXIDE; LIPID-PEROXIDATION; SUPEROXIDE-DISMUTASE; TOPOISOMERASE-II; IRON-CHELATORS; FILTER ELUTION AB Free radical modes of cytotoxicity of streptonigrin (STN) and Adriamycin(R) (ADR) in Chinese hamster V79 cells under aerobic conditions were evaluated using 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TP), a low molecular weight stable nitroxide free radical with antioxidant properties and desferrioxamine (DF), a transition metal chelator. In addition, exogenous superoxide dismutase (SOD, EC 1.15.1.1) and catalase (CAT, EC 1.11.1.6), were tested for cytoprotective effects. EPR studies showed that TP reacts with the semiquinones of both ADR and STN and also with O-2(-) radicals generated during aerobic redox cycling of the respective semiquinone radicals. Pulsed field gel electrophoresis studies confirmed that DNA double-strand breaks (dsb) induced by STN in V79 cells were inhibited completely by TP, whereas ADR-induced DNA dsb were not affected by TP. Clonogenic cell survival studies showed that STN-induced cytotoxicity could be inhibited completely by DF or TP. Both agents were ineffective in inhibiting ADR-induced cytotoxicity. SOD and CAT were ineffective in protecting against both STN and ADR cytotoxicity. Our results are consistent with a mechanism requiring the semiquinone radical intermediate of STN for cytotoxicity and minimal free radical involvement in ADR-induced V79 cell cytotoxicity. C1 NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,RADIAT BIOL BRANCH,BETHESDA,MD 20892. NR 49 TC 38 Z9 40 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD OCT 7 PY 1994 VL 48 IS 7 BP 1427 EP 1435 DI 10.1016/0006-2952(94)90567-3 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PM802 UT WOS:A1994PM80200016 PM 7945443 ER PT J AU CRITCHFIELD, JW WELSH, CJ PHANG, JM YEH, GC AF CRITCHFIELD, JW WELSH, CJ PHANG, JM YEH, GC TI MODULATION OF ADRIAMYCIN(R) ACCUMULATION AND EFFLUX BY FLAVONOIDS IN HCT-15 COLON CELLS - ACTIVATION OF P-GLYCOPROTEIN AS A PUTATIVE MECHANISM SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE P-GLYCOPROTEIN; FLAVONOIDS; QUERCETIN; ADRIAMYCIN; HCT-15 CELLS ID RESISTANCE GENE MDR1; HUMAN-LEUKEMIC CELLS; MULTIDRUG-RESISTANCE; HEAT-SHOCK; QUERCETIN; AGENTS; EXPRESSION; INHIBITION; ENHANCEMENT; TRANSPORT AB Since P-glycoprotein (P-gp) in normal tissues may serve as a cellular defense mechanism against naturally occurring xenobiotics, we considered whether physiologically active components of commonly ingested plant foods could influence P-gp function. To examine this possibility, a series of flavonoids commonly found in plant foods was tested for their ability to modulate [C-14]Adriamycin(R) ([C-14]ADR) accumulation and efflux in P-gp-expressing HCT-15 colon cells. Many flavonoids, in the micromolar range, inhibited the accumulation of [C-14]ADR. Detailed experiments utilizing flavonoids with the greatest activity in reducing [C-14]ADR accumulation, i.e. galangin, kaempferol, and quercetin, revealed that the efflux of [C-14]ADR is increased markedly in the presence of these compounds. Flavonoid-induced stimulation of efflux was rapid and was blocked by the multidrug-resistant (MDR) reversal agents verapamil, vinblastine, and quinidine. The magnitude of flavonoid-stimulated efflux in sodium butyrate-treated cells with a 4-fold induction of P-gp protein was similar to that in uninduced cells. [H-3]Azidopine photoaffinity labeling of P-gp in crude membrane preparations revealed mild to no competition for binding by flavonoids possessing either activity or inactivity in reducing ADR accumulation. Although flavonoid hydrophobicity was found to be unrelated to flavonoid activity in altering [C-14]ADR accumulation, certain structural features were associated with enhancement or diminution of activity. Finally, the significance of flavonoid-related reduction of [C-14]ADR accumulation was underscored in cell growth studies, showing partial protection by quercetin against ADR-induced growth inhibition. It is concluded that certain naturally occurring plant flavonoids may acutely upregulate the apparent activity of P-gp. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC PREVENT & CONTROL,NUTR & MOLEC REGULAT LAB,FREDERICK,MD 21702. NR 32 TC 148 Z9 149 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD OCT 7 PY 1994 VL 48 IS 7 BP 1437 EP 1445 DI 10.1016/0006-2952(94)90568-1 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PM802 UT WOS:A1994PM80200017 PM 7945444 ER PT J AU TSAI, CH DOONG, SL JOHNS, DG DRISCOLL, JS CHENG, YC AF TSAI, CH DOONG, SL JOHNS, DG DRISCOLL, JS CHENG, YC TI EFFECT OF ANTI-HIV 2'-BETA-FLUORO-2',3'-DIDEOXYNUCLEOSIDE ANALOGS ON THE CELLULAR CONTENT OF MITOCHONDRIAL-DNA AND ON LACTATE PRODUCTION SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE ANTI HIV NUCLEOSIDE; MITOCHONDRIA DNA; LACTATE ID HUMAN-IMMUNODEFICIENCY-VIRUS; REPLICATION; ZIDOVUDINE; TOXICITY; AIDS AB Many dideoxynucleosides that are effective against human immunodeficiency virus (HIV) also are potent inhibitors of mitochondrial DNA (mtDNA) synthesis, and the resulting mtDNA decrease could be responsible for the delayed clinical toxicity sometimes observed with these drugs. The following compounds have been examined for their toxicity to human lymphoid CEM cells, and their ability to suppress mtDNA content: 2',3'-dideoxycytidine (ddC), 2',3'-dideoxyadenosine (ddA), 2',3'-dideoxyinosine (ddI) and 2',3'-dideoxyguanosine (ddG); and their 2'-beta-fluoro analogs; beta-F-ddC, beta-F-ddA, beta-F-ddI and beta-F-ddG. Two other fluoro analogs, 5-F-ddC and 2'-beta,5-di-F-ddC were also examined. The ratio of C-IC50 (concentration that inhibited cell growth by 50%) to mt-IC50 (concentration that inhibited mtDNA synthesis by 50%) was determined for each compound. The rank-order of this ratio was ddC > 5-F-ddC much greater than ddA > ddI > ddG > beta-F-ddC > beta-F-ddA > beta-F-ddG with the highest ratios indicating the greatest potential for delayed toxicity. In comparison with ddC, beta-F-ddC and beta-F-ddA were 5,000 and 22,000 times less potent, respectively, in suppressing cellular mtDNA content, while their anti-HIV potencies were decreased only modestly relative to their unfluorinated parent compounds. beta F-ddI and 2'-beta,5-di-F-ddC produced neither cellular toxicity nor mtDNA suppression at concentrations of 500 and 1000 mu M, respectively. Lactic acid, the product of compensatory glycolysis that results from the inhibition of mitochondrial oxidative phosphorylation, was measured after cells were treated with these compounds. There appears to be a concentration-related correlation between the increase of lactic acid and the extent of mtDNA inhibition for the compounds examined. C1 YALE UNIV,SCH MED,DEPT PHARMACOL,NEW HAVEN,CT 06510. NCI,MED CHEM LAB,BETHESDA,MD 20892. OI DOONG, SHIN-LIAN/0000-0002-0936-3858 FU NCI NIH HHS [CA44358] NR 29 TC 35 Z9 35 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD OCT 7 PY 1994 VL 48 IS 7 BP 1477 EP 1481 DI 10.1016/0006-2952(94)90573-8 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PM802 UT WOS:A1994PM80200022 PM 7945448 ER PT J AU CHANOCK, SJ ELBENNA, J SMITH, RM BABIOR, BM AF CHANOCK, SJ ELBENNA, J SMITH, RM BABIOR, BM TI THE RESPIRATORY BURST OXIDASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID CHRONIC GRANULOMATOUS-DISEASE; CELL-FREE SYSTEM; NEUTROPHIL NADPH OXIDASE; CYTOCHROME-B; BINDING SITE; CYTOSOLIC COMPONENTS; GUANINE-NUCLEOTIDES; PHAGOCYTE OXIDASE; HYDROGEN-PEROXIDE; INTERFERON-GAMMA C1 SCRIPPS RES INST, DEPT MOLEC & EXPTL MED, LA JOLLA, CA 92037 USA. UNIV CALIF SAN DIEGO, SCH MED, DEPT MED, LA JOLLA, CA 92093 USA. RP CHANOCK, SJ (reprint author), NCI, PEDIAT BRANCH, BETHESDA, MD 20892 USA. FU NIAID NIH HHS [AI-24227, AI-24838, AI-28479] NR 75 TC 445 Z9 454 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 7 PY 1994 VL 269 IS 40 BP 24519 EP 24522 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ490 UT WOS:A1994PQ49000001 PM 7929117 ER PT J AU BAUKAL, AJ HUNYADY, L CATT, KJ BALLA, T AF BAUKAL, AJ HUNYADY, L CATT, KJ BALLA, T TI EVIDENCE FOR PARTICIPATION OF CALCINEURIN IN POTENTIATION OF AGONIST-STIMULATED CYCLIC-AMP FORMATION BY THE CALCIUM-MOBILIZING HORMONE, ANGIOTENSIN-II SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID ADRENAL GLOMERULOSA CELLS; PROTEIN-KINASE-C; PHORBOL ESTER TREATMENT; ADENYLATE-CYCLASE; SIGNALING PATHWAYS; EXPRESSION; RECEPTOR; CLONING; GS; METABOLISM AB Angiotensin II (AII) receptors are known to interact with two distinct guanine nucleotide binding proteins, G(q/11) and G(i), in rat adrenal glomerulosa cells to activate phospholipase C and to inhibit adenylate cyclase, respectively. However, in cultured bovine glomerulosa cells AII potentiates rather than inhibits the stimulatory effect of adrenocorticotropin (ACTH) on cAMP levels. This effect of AII was partially mimicked by phorbol 12-myristate 13-acetate (PMA) and was partially inhibited by staurosporine or depletion of protein kinase C but was unaffected by pertussis toxin treatment. No potentiation was detectable in disrupted cells or in membrane preparations. In intact glomerulosa cells, treatment with cyclosporin A or FK506 completely inhibited AII- or PMA-induced potentiation of cAMP production without affecting the response to ACTH. In COS-7 cells transfected with the rat AT(1) receptor, AII caused 2-3-fold enhancement of the ACTH-induced cAMP response, an effect that was partially reproduced by PMA. These potentiating actions of AII and PMA were prevented by preincubation with cyclosporin A or FK506, and the latter effect was abolished by rapamycin. These results implicate the Ca2+- and calmodulin-dependent protein phosphatase, calcineurin, in AII-induced enhancement of adenylate cyclase activity in both adrenal glomerulosa and transfected COS-7 cells. The finding that AII enhances ACTH stimulated production of cAMP by a second messenger-mediated mechanism that involves the participation of calcineurin reveals an additional mode of cross-talk between pathways activated by Ca2+-mobilizing and cAMP-generating receptors. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. OI Balla, Tamas/0000-0002-9077-3335 NR 28 TC 47 Z9 47 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 OCT 7 PY 1994 VL 269 IS 40 BP 24546 EP 24549 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ490 UT WOS:A1994PQ49000008 PM 7929124 ER PT J AU OLAH, ME JACOBSON, KA STILES, GL AF OLAH, ME JACOBSON, KA STILES, GL TI ROLE OF THE 2ND EXTRACELLULAR LOOP OF ADENOSINE RECEPTORS IN AGONIST AND ANTAGONIST BINDING - ANALYSIS OF CHIMERIC A(1)/A(3)-ADENOSINE RECEPTORS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; MOLECULAR-CLONING; LIGAND-BINDING; HUMAN BRAIN; ADENOSINE-A1-RECEPTOR CDNA; NEUROKININ-1 RECEPTOR; HIGH-AFFINITY; RAT-BRAIN; EXPRESSION; A1 AB Adenosine receptor (AR) agonists and antagonists are similar to 100-fold and 100,000-fold, respectively, more potent at the bovine A(1)AR as compared to the rat A(3)AR. To determine regions of ARs involved in ligand recognition, chimeric receptors composed of bovine A(1)AR and rat A(3)AR sequence were constructed and their ligand binding properties examined following expression in COS-7 cells. Substitutions of the second extracellular loop or a region encompassing transmembrane domains 6 and 7 of the A(1)AR into the A(3)AR resulted in enhanced affinities of both agonists and antagonists compared to wild-type A(3)AR. The region of the second extracellular loop of the A(1)AR responsible for this effect was identified as the distal eleven amino acids of the loop. Replacement of this segment of the A(3)AR with that of the A(1)AR in combination with the regions encompassing transmembrane domains 6 and 7 resulted in a 50,000-fold increase in the K-d for antagonist radioligand, [H-3]1,3-dipropyl-8-cyclopentylxanthine. Agonist affinity at this chimeric was over 100-fold greater than that displayed by wild-type A(3)AR. Thus, multiple regions of ARs including a segment of the second extracellular loop are involved in ligand recognition, and considerable overlap exists in structural features required for agonist and antagonist binding. C1 DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT PHARMACOL,DURHAM,NC 27710. NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999]; NHLBI NIH HHS [NHLBI P50HL17670, NHLBI RO1HL35134] NR 46 TC 85 Z9 86 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 OCT 7 PY 1994 VL 269 IS 40 BP 24692 EP 24698 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ490 UT WOS:A1994PQ49000029 PM 7929142 ER PT J AU RANJAN, M WONG, JM SHI, YB AF RANJAN, M WONG, JM SHI, YB TI TRANSCRIPTIONAL REPRESSION OF XENOPUS TR-BETA GENE IS MEDIATED BY A THYROID-HORMONE RESPONSE ELEMENT LOCATED NEAR THE START SITE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RETINOIC-ACID RECEPTOR; HUMAN GLUCOCORTICOID RECEPTOR; X-RECEPTOR; AMPHIBIAN METAMORPHOSIS; PREINITIATION COMPLEX; GENOMIC STRUCTURE; ONCOGENE PRODUCT; MESSENGER-RNA; EXPRESSION; PROTEIN AB We report here the detailed analysis of the promoter of a thyroid hormone receptor (TR) gene that is regulated by the hormone itself. The receptor gene, TR beta A, is one of the two TR beta genes in Xenopus laevis. It has two transcription start sites. The mRNAs derived from one of them are up-regulated by thyroid hormone, whereas those derived from the other are independent of the hormone. We have characterized the hormone inducible promoter using a transient transfection assay in a Xenopus tissue culture cell line (A6). Deletion and mutational analysis identifies the first amphibian thyroid hormone response element (TRE). This TRE consists of near perfect direct repeats of AGGTCA with a 4-base pair spacing similar to mammalian TREs. The TRE forms specific complexes with extracts of A6 cells that have similar sequence specificities as those found for the complexes between mammalian TRs and TREs. However, unlike TREs found in other thyroid hormone-inducible promoters, this TRE is located at the putative transcription start site and mediates transcriptional repression by unliganded TRs. The addition of thyroid hormone at physiological concentrations overcomes the repression and induces further transcriptional activation at higher concentrations. These results suggest a potential mechanism for the regulation of amphibian metamorphosis, a process that is entirely controlled by thyroid hormone. C1 NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. NR 56 TC 139 Z9 140 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 7 PY 1994 VL 269 IS 40 BP 24699 EP 24705 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ490 UT WOS:A1994PQ49000030 PM 7929143 ER PT J AU AOTA, S NOMIZU, M YAMADA, KM AF AOTA, S NOMIZU, M YAMADA, KM TI THE SHORT AMINO-ACID-SEQUENCE PRO-HIS-SER-ARG-ASN IN HUMAN FIBRONECTIN ENHANCES CELL-ADHESIVE FUNCTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; BINDING DOMAIN; III MODULE; POLYMERASE; REGIONS; PROTEIN; RGD AB Synergistic sites in the central cell-adhesive domain of fibronectin (FN) substantially enhance cell adhesion mediated by the alpha(5) beta(1) integrin receptor for fibronectin. We characterized a critical minimal sequence needed for synergistic activity using site directed mutagenesis and homology scanning using intramolecular chimeras. The minimal cell-binding domain of FN consisting of the 9th and 10th type III FN repeat was expressed in an Escherichia coli expression system. This protein retained high biological activity when assayed using a competitive inhibition assay for FN-mediated adhesion of baby hamster kidney or HT-1080 cells. In contrast, a construct consisting of the 8th and 10th repeat displayed very low biological activity. By replacing various portions of the 8th repeat with homologous 9th repeat segments, we mapped the synergistic region to the center of the 9th repeat. When a very short peptide sequence, Pro-His-Ser-Arg-Asn (PHSRN), from the 9th repeat was substituted for the homologous pentapeptide site in the 8th repeat sequence, the recombinant protein showed markedly enhanced activity. Further mutagenesis analysis suggested that the arginine residue of this pentapeptide sequence is important for function. We also identified a weaker adjacent synergy region other than the PHSRN region, Epitope mapping of an anti-FN monoclonal antibody that inhibits FN-mediated adhesion identified the same critical regions. A synthetic peptide containing the PHSRN sequence showed neither competitive inhibitory activity in solution nor synergy with a soluble RGD-containing peptide. However, when the same synthetic peptide was positioned via a covalent bond at the corresponding site of the normally inactive 8th repeat, it mediated an enhancement of adhesive activity. These results identify a pentapeptide site that synergistically enhances the cell-adhesive activity of the FN RGD sequence. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. OI Yamada, Kenneth/0000-0003-1512-6805 NR 22 TC 445 Z9 447 U1 2 U2 30 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 OCT 7 PY 1994 VL 269 IS 40 BP 24756 EP 24761 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ490 UT WOS:A1994PQ49000039 PM 7929152 ER PT J AU HUNYADY, L BAUKAL, AJ BALLA, T CATT, KJ AF HUNYADY, L BAUKAL, AJ BALLA, T CATT, KJ TI INDEPENDENCE OF TYPE-I ANGIOTENSIN-II RECEPTOR ENDOCYTOSIS FROM G-PROTEIN COUPLING AND SIGNAL-TRANSDUCTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-ADRENERGIC-RECEPTOR; ADRENAL GLOMERULOSA CELLS; SMOOTH-MUSCLE CELLS; MEDIATED ENDOCYTOSIS; POTENTIAL MECHANISM; CARBOXYL-TERMINUS; INTERNALIZATION; SEQUESTRATION; MUTAGENESIS; GENERATION AB The relationship between angiotensin II-induced activation of G proteins and receptor internalization was analyzed by transiently expressing mutant and wild type cDNAs for the rat AT(1a) receptor in COS-7 cells. Pertussis toxin-sensitive G proteins did not appear to play a role in endocytosis since the receptor showed normal internalization kinetics in pertussis toxin-treated cells. Three deletion mutants of the third cytoplasmic loop revealed that the N-terminal part of this region is important for both receptor endocytosis and intracellular signaling. Three point mutations of Asp(74), which has been implicated in signal transduction by the AT(1a) receptor, caused impaired G protein coupling and inositol phosphate responses. However, each of these mutants (D74N, D74H, and D74Y) showed markedly different internalization kinetics. The D74Y mutant showed the greatest impairment of internalization but retained the highest degree of inositol phosphate stimulation. In contrast, the D74N mutant, which showed the most impaired G protein coupling and inositol phosphate responses, had similar internalization kinetics to the wild type receptor. The combined mutant receptor containing the D74N substitution and deletion of residues 221-226 from the third cytoplasmic loop showed no G protein coupling or inositol phosphate response but was internalized about 60% as rapidly as the wild type receptor. These data demonstrate that endocytosis of the AT(1) receptor is independent of agonist-activated signal transduction and indicate that receptor internalization and activation of phospholipase C have different structural requirements. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. OI Balla, Tamas/0000-0002-9077-3335 NR 35 TC 125 Z9 125 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 OCT 7 PY 1994 VL 269 IS 40 BP 24798 EP 24804 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ490 UT WOS:A1994PQ49000045 PM 7929158 ER PT J AU ABUGO, OO RIFKIND, JM AF ABUGO, OO RIFKIND, JM TI OXIDATION OF HEMOGLOBIN AND THE ENHANCEMENT PRODUCED BY NITROBLUE TETRAZOLIUM SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DISTAL HISTIDINE; NUCLEOPHILIC DISPLACEMENT; COLORIMETRIC ASSAY; AUTOXIDATION; SUPEROXIDE; MECHANISM; OXYHEMOGLOBIN; OXYMYOGLOBIN; MYOGLOBIN; AUTOOXIDATION AB The autoxidation of hemoglobin as a function of oxygen pressure and the effect of added nitroblue tetrazolium have been studied. It has been shown that the enhanced autoxidation at intermediate oxygen pressures can only be partially explained by the outer-sphere reaction of oxygen with deoxygenated chains. An additional enhancement associated with the properties of partially oxygenated hemoglobins has been attributed to the mobility on the distal side of the heme which facilitates the nucleophilic displacement of bound oxygen by the distal histidine. Nitroblue tetrazolium, in addition to reacting with the superoxide formed during autoxidation, is shown to oxidize directly both deoxygenated and oxygenated hemoglobin in two steps, proceeding through the one electron reduced intermediate, a tetrazolinyl radical. Even though the oxygenated chains are oxidized by nitroblue tetrazolium, much less overall reduction of nitroblue tetrazolium is observed at high oxygen pressures. This phenomenon is attributed to the reoxidation by oxygen of both the tetrazolinyl radical and the formazan. The reaction with nitroblue tetrazolium is also found to con tribute to enhanced oxidation at intermediate oxygen pressures. This behavior is explained by the two-electron reaction with nitroblue tetrazolium and the oxygen dependence of the various processes involved in the reaction of nitroblue tetrazolium. C1 NIA,GERONTOL RES CTR,CELLULAR & MOLEC BIOL LAB,MOLEC DYNAM SECT,BALTIMORE,MD 21224. 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 OCT 7 PY 1994 VL 269 IS 40 BP 24845 EP 24853 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ490 UT WOS:A1994PQ49000051 PM 7929164 ER PT J AU PRUSS, D REEVES, R BUSHMAN, FD WOLFFE, AP AF PRUSS, D REEVES, R BUSHMAN, FD WOLFFE, AP TI THE INFLUENCE OF DNA AND NUCLEOSOME STRUCTURE ON INTEGRATION EVENTS DIRECTED BY HIV INTEGRASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID I-HYPERSENSITIVE SITES; TRANSFER-RNA GENE; RETROVIRAL INTEGRATION; ESCHERICHIA-COLI; B-DNA; TRANSCRIPTION COMPLEXES; PREFERRED TARGETS; KINETOPLAST DNA; SEQUENCE; CHROMATIN AB DNA copies of the human immunodeficiency virus (HIV) genome integrate nonrandomly into the chromosomal DNA of the host cell. In this report, we investigate the molecular basis of this selectivity using the virus-encoded HIV integrase to direct integration of a synthetic HIV long terminal repeat substrate into either DNA molecules of known structure or previously defined nucleosomal complexes. We find that the structure of the target greatly influences the site of integration, and, moreover, DNA curvature, flexibility, and rigidity in solution all influence the frequency of integration. Importantly, for DNA with all of these properties, the distortion of the double helix directed by association with the histone proteins promotes the integration reaction and alters the distribution of sites that are selected for integration. We suggest that both intrinsic DNA structure and the folding of DNA into chromosomal structures will exert a major influence on target site selection for integration of the viral genome. C1 SALK INST BIOL STUDIES,INFECT DIS LAB,LA JOLLA,CA 92014. RP PRUSS, D (reprint author), NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892, USA. NR 65 TC 135 Z9 135 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 OCT 7 PY 1994 VL 269 IS 40 BP 25031 EP 25041 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ490 UT WOS:A1994PQ49000077 PM 7929189 ER PT J AU WEINMANN, W PARKER, CE DETERDING, LJ PAPAC, DI HOYES, J PRZYBYLSKI, M TOMER, KB AF WEINMANN, W PARKER, CE DETERDING, LJ PAPAC, DI HOYES, J PRZYBYLSKI, M TOMER, KB TI CAPILLARY ELECTROPHORESIS-MATRIX-ASSISTED LASER-DESORPTION IONIZATION MASS-SPECTROMETRY OF PROTEINS SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 6th International Symposium on High Performance Capillary Electrophoresis (HPCE 94) CY JAN 31-FEB 03, 1994 CL SAN DIEGO, CA ID ZONE ELECTROPHORESIS; PEPTIDES AB An ''off-line'' combination of capillary electrophoresis (CE) with matrix-assisted laser-desorption mass spectrometry (MALDI-MS) has been developed for the structural characterization of CE-separated peptides and proteins. Using a sheath flow interface, similar to that developed for ''on-line'' CE-fast atom bombardment MS and CE-electrospray MS, an efficient sample isolation procedure has been developed which is applicable to bioorganic compounds in aqueous buffer solutions. This isolation procedure, with subsequent transfer to the MALDI-MS sample target, has been successfully used for the direct analysis of CE-separated proteins of M(r) up to 67 000, and a mixture of apolipoprotein AII monomer and homodimer, using sample amounts of less than 1 pmol. C1 NIEHS, MOLEC BIOPHYS LAB, RES TRIANGLE PK, NC 27709 USA. UNIV KONSTANZ, FAC CHEM, D-78434 CONSTANCE, GERMANY. VG ANALYT, MANCHESTER M23 9LE, LANCS, ENGLAND. RI Tomer, Kenneth/E-8018-2013 NR 19 TC 47 Z9 48 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD OCT 7 PY 1994 VL 680 IS 2 BP 353 EP 361 DI 10.1016/0021-9673(94)85131-X PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PM250 UT WOS:A1994PM25000001 ER PT J AU FARNSWORTH, DW WINK, DA ROSCHER, NM MICHEJDA, CJ SMITH, RH AF FARNSWORTH, DW WINK, DA ROSCHER, NM MICHEJDA, CJ SMITH, RH TI DECOMPOSITION OF PYRIDINYLTRIAZENES IN AQUEOUS BUFFER - A KINETIC AND MECHANISTIC INVESTIGATION SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID ACID-CATALYZED DECOMPOSITION; 1,3-DIALKYLTRIAZENES; ALKYLARYLTRIAZENES; TRIALKYLTRIAZENES; IONS AB 1-(X-pyridinyl)-3-butyltriazenes (X-PBT), where X = 2, 3, or 4, were prepared as prototypes of new chemotherapeutic agents. The acid-catalyzed decomposition of the 1-(X-pyridinyl)-3-butyltriazenes leads to the formation ofthe corresponding aminopyridines and butyl alcohols. pH-rate profiles, determined over a pH range of 3.5-12.00, show sigmoidal curves with slopes asymptotically approaching 0 at the extremes. The transitions have slopes where rate is inversely proportional to pH, indicating regions of acid catalysis. The solvent kinetic isotope effect, k(H2O)/k(D2O), for each reaction is <1.0. The determination ofthe kinetics ofthe decomposition in amino buffers, ranging in pK(a) from 8.95 to 10.4 and concentrations from 0.03 to 0.15 M, indicates negligible variation in the rate constant. These data strongly support the conclusion that the decomposition is specific acid catalyzed (A1) for each X-PBT isomer. This implies that the reactions involve fast, reversible protonation followed by the rate-determining heterolysis of the protonated species to the n-butyldiazonium ion and X-aminopyridine. Near neutral pH, the half-lives ofthe 2- and 4-isomers are similar to 100-fold shorter than that of the 3-isomer. This difference can be explained by protonation of the pyridinyl N, which leads to direct dissociation only for the 2- and 4-isomers. Experimental pK(a')'s were obtained for each isomer: 2-PBT, 5.19 +/- 0.19; 3-PBT, 4.89 +/- 0.12; 4-PBT, 7.77 +/- 0.16. These values are lower than, but follow the same order as, the pK(a) values for the analogous isomers of aminopyridine. C1 WESTERN MARYLAND COLL,DEPT CHEM,WESTMINSTER,MD 21157. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,CHEM SECT,FREDERICK,MD 21702. AMERICAN UNIV,DEPT CHEM,WASHINGTON,DC 20016. RP FARNSWORTH, DW (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC ASPECTS DRUG DESIGN SECT,FREDERICK,MD 21702, USA. NR 42 TC 7 Z9 7 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD OCT 7 PY 1994 VL 59 IS 20 BP 5942 EP 5950 DI 10.1021/jo00099a024 PG 9 WC Chemistry, Organic SC Chemistry GA PK513 UT WOS:A1994PK51300024 ER PT J AU MORRISON, D AF MORRISON, D TI 14-3-3 - MODULATORS OF SIGNALING PROTEINS SO SCIENCE LA English DT Editorial Material ID AERUGINOSA EXOENZYME-S; PSEUDOMONAS-AERUGINOSA; FAMILY; RAS RP MORRISON, D (reprint author), NCI,FREDERICK CANC RES & DEV CTR,MOLEC MECHANISMS CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. NR 26 TC 182 Z9 184 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 OCT 7 PY 1994 VL 266 IS 5182 BP 56 EP 57 DI 10.1126/science.7939645 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PK582 UT WOS:A1994PK58200024 PM 7939645 ER PT J AU MIKI, Y SWENSEN, J SHATTUCKEIDENS, D FUTREAL, PA HARSHMAN, K TAVTIGIAN, S LIU, QY COCHRAN, C BENNETT, LM DING, W BELL, R ROSENTHAL, J HUSSEY, C TRAN, T MCCLURE, M FRYE, C HATTIER, T PHELPS, R HAUGENSTRANO, A KATCHER, H YAKUMO, K GHOLAMI, Z SHAFFER, D STONE, S BAYER, S WRAY, C BOGDEN, R DAYANANTH, P WARD, J TONIN, P NAROD, S BRISTOW, PK NORRIS, FH HELVERING, L MORRISON, P ROSTECK, P LAI, M BARRETT, JC LEWIS, C NEUHAUSEN, S CANNONALBRIGHT, L GOLDGAR, D WISEMAN, R KAMB, A SKOLNICK, MH AF MIKI, Y SWENSEN, J SHATTUCKEIDENS, D FUTREAL, PA HARSHMAN, K TAVTIGIAN, S LIU, QY COCHRAN, C BENNETT, LM DING, W BELL, R ROSENTHAL, J HUSSEY, C TRAN, T MCCLURE, M FRYE, C HATTIER, T PHELPS, R HAUGENSTRANO, A KATCHER, H YAKUMO, K GHOLAMI, Z SHAFFER, D STONE, S BAYER, S WRAY, C BOGDEN, R DAYANANTH, P WARD, J TONIN, P NAROD, S BRISTOW, PK NORRIS, FH HELVERING, L MORRISON, P ROSTECK, P LAI, M BARRETT, JC LEWIS, C NEUHAUSEN, S CANNONALBRIGHT, L GOLDGAR, D WISEMAN, R KAMB, A SKOLNICK, MH TI A STRONG CANDIDATE FOR THE BREAST AND OVARIAN-CANCER SUSCEPTIBILITY GENE BRCA1 SO SCIENCE LA English DT Article ID FAMILIAL BREAST; ZINC FINGER; WILMS-TUMOR; ATAXIA-TELANGIECTASIA; DNA-BINDING; WT1 GENE; CHROMOSOME-17Q21; IDENTIFICATION; MUTATIONS; P53 AB A strong candidate for the 17q-linked BRCA1 gene, which influences susceptibility to breast and ovarian cancer, has been identified by positional cloning methods. Probable predisposing mutations have been detected in five of eight kindreds presumed to segregate BRCA1 susceptibility alleles. The mutations include an 11-base pair deletion, a 1-base pair insertion, a stop codon, a missense substitution, and an inferred regulatory mutation. The BRCA1 gene is expressed in numerous tissues, including breast and ovary, and encodes a predicted protein of 1863 amino acids. This protein contains a zinc finger domain in its amino-terminal region, but is otherwise unrelated to previously described proteins, identification of BRCA1 should facilitate early diagnosis of breast and ovarian cancer susceptibility in some individuals as well as a better understanding of breast cancer biology. C1 UNIV UTAH,MED CTR,DEPT MED INFORMAT,SALT LAKE CITY,UT 84132. MYRIAD GENET,SALT LAKE CITY,UT 84108. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. UNIV UTAH,MED CTR,DEPT INTERNAL MED,SALT LAKE CITY,UT 84132. MCGILL UNIV,DEPT MED GENET,MONTREAL H3G 1A4,PQ,CANADA. ELI LILLY & CO,LILLY RES LABS,INDIANAPOLIS,IN 46285. UNIV UTAH,MED CTR,DEPT MED INFORMAT,SALT LAKE CITY,UT 84108. RI Lewis, Cathryn/A-5225-2010; OI Lewis, Cathryn/0000-0002-8249-8476; albright, lisa/0000-0003-2602-3668 FU NCI NIH HHS [CA-48711, CA-54936, CA-55914] NR 44 TC 3972 Z9 4092 U1 32 U2 288 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 7 PY 1994 VL 266 IS 5182 BP 66 EP 71 DI 10.1126/science.7545954 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PK582 UT WOS:A1994PK58200026 PM 7545954 ER PT J AU WANG, MH RONSIN, C GESNEL, MC COUPEY, L SKEEL, A LEONARD, EJ BREATHNACH, R AF WANG, MH RONSIN, C GESNEL, MC COUPEY, L SKEEL, A LEONARD, EJ BREATHNACH, R TI IDENTIFICATION OF THE RON GENE-PRODUCT AS THE RECEPTOR FOR THE HUMAN MACROPHAGE STIMULATING PROTEIN SO SCIENCE LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; TYROSINE KINASE; SCATTER FACTOR; MET PROTOONCOGENE; CELL CARCINOMA; SHORT ARM; C-MET; CHROMOSOME-3; EXPRESSION; HOMOLOGY AB Macrophage-stimulating protein (MSP) is a member of the hepatocyte growth factor-scatter factor (HGF-SF) family. Labeled MSP bound to Madin-Darby canine kidney (MDCK) cells transfected with complementary DNA encoding Ron, a cell membrane protein tyrosine kinase. Cross-lin king of I-125-labeled MSP to transfected cells (MDCK-RE7 cells) and immunoprecipitation by antibodies to Ron revealed a 220-kilodalton complex, a size consistent with that of MSP (80 kilodaltons) cross-linked to the beta chain of Ron (150 kilodaltons). The binding of I-125-labeled MSP to MDCK-RE7 cells was inhibited by unlabeled MSP, but not by HGF-SF. MSP caused phosphorylation of the beta chain of Ron and induced migration of MDCK-RE7 cells. These results establish the ron gene product as a specific cell-surface receptor tor MSP. C1 CHR NANTES,INST BIOL,INSERM,U211,F-44035 NANTES 01,FRANCE. FAC MED LIMOGES,HEMATOL EXPTL LAB,F-87025 LIMOGES,FRANCE. RP WANG, MH (reprint author), NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,IMMUNOPATHOL SECT,FREDERICK,MD 21702, USA. RI Breathnach, Richard/K-7599-2015 NR 25 TC 216 Z9 224 U1 0 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 7 PY 1994 VL 266 IS 5182 BP 117 EP 119 DI 10.1126/science.7939629 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PK582 UT WOS:A1994PK58200037 PM 7939629 ER PT J AU FUTREAL, PA LIU, QY SHATTUCKEIDENS, D COCHRAN, C HARSHMAN, K TAVTIGIAN, S BENNETT, LM HAUGENSTRANO, A SWENSEN, J MIKI, Y EDDINGTON, K MCCLURE, M FRYE, C WEAVERFELDHAUS, J DING, W GHOLAMI, Z SODERKVIST, P TERRY, L JHANWAR, S BERCHUCK, A IGLEHART, JD MARKS, J BALLINGER, DG BARRETT, JC SKOLNICK, MH KAMB, A WISEMAN, R AF FUTREAL, PA LIU, QY SHATTUCKEIDENS, D COCHRAN, C HARSHMAN, K TAVTIGIAN, S BENNETT, LM HAUGENSTRANO, A SWENSEN, J MIKI, Y EDDINGTON, K MCCLURE, M FRYE, C WEAVERFELDHAUS, J DING, W GHOLAMI, Z SODERKVIST, P TERRY, L JHANWAR, S BERCHUCK, A IGLEHART, JD MARKS, J BALLINGER, DG BARRETT, JC SKOLNICK, MH KAMB, A WISEMAN, R TI BRCA1 MUTATIONS IN PRIMARY BREAST AND OVARIAN CARCINOMAS SO SCIENCE LA English DT Article ID FAMILIAL BREAST; ALLELE LOSSES; CANCER; REGION; CHROMOSOME-17Q; TUMORS; PROGRESSION; LINKAGE AB Loss of heterozygosity data from familial tumors suggest that BRCA1, a gene that confers susceptibility to ovarian and early-onset breast cancer, encodes a tumor suppressor. The BRCA1 region is also subject to allelic loss in sporadic breast and ovarian cancers, an indication that BRCA1 mutations may occur somatically in these tumors. The BRCA1 coding region was examined for mutations in primary breast and ovarian tumors that show allele loss at the BRCA1 locus. Mutations were detected in 3 of 32 breast and 1 of 12 ovarian carcinomas; all four mutations were germline alterations and occurred in early-onset cancers. These results suggest that mutation of BRCA1 may not be critical in the development of the majority of breast and ovarian cancers that arise in the absence of a mutant germline allele. C1 MYRIAD GENET,SALT LAKE CITY,UT 84108. UNIV UTAH,MED CTR,DEPT MED INFORMAT,SALT LAKE CITY,UT 84123. FAC HLTH SCI LINKOPING,DEPT OCCUPAT MED,S-58185 LINKOPING,SWEDEN. MEM SLOAN KETTERING CANC CTR,DEPT HUMAN GENET,NEW YORK,NY 10021. DUKE UNIV,MED CTR,DEPT GYNECOL ONCOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT SURG,DURHAM,NC 27710. RP FUTREAL, PA (reprint author), NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709, USA. FU NCI NIH HHS [CA48711, CA55914, CA56749] NR 23 TC 977 Z9 991 U1 4 U2 33 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 7 PY 1994 VL 266 IS 5182 BP 120 EP 122 DI 10.1126/science.7939630 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PK582 UT WOS:A1994PK58200038 PM 7939630 ER PT J AU RANDAD, RS NAIK, RH GULNIK, SV YU, B ERICKSON, JW AF RANDAD, RS NAIK, RH GULNIK, SV YU, B ERICKSON, JW TI SYMMETRY-BASED HIV PROTEASE INHIBITORS CONTAINING A HYDROXY BIS-UREA ISOSTERE SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID RETROVIRAL PROTEASES; CRYSTAL-STRUCTURE; IMMUNODEFICIENCY RP RANDAD, RS (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702, USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD OCT 6 PY 1994 VL 4 IS 19 BP 2343 EP 2346 DI 10.1016/0960-894X(94)85037-2 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA PK888 UT WOS:A1994PK88800016 ER PT J AU PANZA, JA AF PANZA, JA TI ENDOTHELIUM-DEPENDENT VASODILATATION AND ESSENTIAL-HYPERTENSION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP PANZA, JA (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 4 TC 4 Z9 4 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 OCT 6 PY 1994 VL 331 IS 14 BP 951 EP 951 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PJ419 UT WOS:A1994PJ41900026 PM 8078567 ER PT J AU CORTI, MC GURALNIK, JM SALIVE, ME SORKIN, JD AF CORTI, MC GURALNIK, JM SALIVE, ME SORKIN, JD TI SERUM-ALBUMIN LEVEL AND PHYSICAL-DISABILITY AS PREDICTORS OF MORTALITY IN OLDER PERSONS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORONARY HEART-DISEASE; HOSPITAL STAY; COMPLICATIONS; AGE AB Objectives.-To study the relationship between serum albumin level and all-cause mortality in an elderly population and to evaluate the role of albumin level in combination with physical disability status in predicting mortality. Design.-Cohort study with a mean follow-up of 3.7 years. Setting.-Three communities: East Boston, Mass, New Haven, Conn, and Iowa and Washington counties, Iowa. Subjects.-A total of 1486 men and 2630 women aged 71 years and older who consented to have blood drawn. Results.-During follow-up, 447 men and 488 women died. In both sexes, there was a graded increase in mortality rate with decreasing albumin level. After adjusting for age, race, education, chronic conditions, and disability status, hypoalbuminemia (<35 g/L) was associated with a significantly increased risk of mortality in comparison with the reference group tie, those with albumin levels greater than 43 g/L) (men: relative risk [RR], 1.9; 95% confidence interval [Cl], 1.1 to 3.1; women: RR, 3.7; 95% Cl, 2.5 to 5.5). Among those with albumin levels in the range usually considered normal (35 g/L to 50 g/L), there was a graded increase in mortality risk from the highest normal to the lowest normal groups. For women, results were similar in separate analyses that considered deaths occurring during the first year end 1 year or more after baseline, while for men the relationship decreased after 1 year. Lower albumin level was associated with an elevated risk of mortality for all categories of causes of death. A 15-lever measure that characterized participants according to albumin level and disability status demonstrated that mortality increased with decreasing albumin level and increasing disability lever. Conclusions.-Serum albumin level is an independent risk factor for all-cause mortality in older persons. A combined measure of albumin and disability reveals a strong gradient in mortality risk and may serve as a simple but useful index of frailty that can identify a high-risk group of older men and women who could be targeted for preventive and treatment efforts. RP CORTI, MC (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,7201 WISCONSIN AVE,ROOM 3C-309,BETHESDA,MD 20892, USA. FU NIA NIH HHS [N01-AG-0-2107, N01-AG-0-2105, N01-AG-0-2106] NR 38 TC 362 Z9 364 U1 0 U2 12 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 OCT 5 PY 1994 VL 272 IS 13 BP 1036 EP 1042 DI 10.1001/jama.272.13.1036 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA PH775 UT WOS:A1994PH77500029 PM 8089886 ER PT J AU TRAVIS, LB CURTIS, RE STOVALL, M HOLOWATY, EJ VANLEEUWEN, FE GLIMELIUS, B LYNCH, CF HAGENBEEK, A LI, CY BANKS, PM GOSPODAROWICZ, MK ADAMI, J WACHOLDER, S INSKIP, PD TUCKER, M BOICE, JD AF TRAVIS, LB CURTIS, RE STOVALL, M HOLOWATY, EJ VANLEEUWEN, FE GLIMELIUS, B LYNCH, CF HAGENBEEK, A LI, CY BANKS, PM GOSPODAROWICZ, MK ADAMI, J WACHOLDER, S INSKIP, PD TUCKER, M BOICE, JD TI RISK OF LEUKEMIA FOLLOWING TREATMENT FOR NON-HODGKINS-LYMPHOMA SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ACUTE NONLYMPHOCYTIC LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; ADVANCED BREAST-CANCER; THERAPY-RELATED LEUKEMIA; 2ND MALIGNANT NEOPLASMS; COMBINATION CHEMOTHERAPY; ALKYLATING-AGENTS; MYELODYSPLASTIC SYNDROMES; OVARIAN-CANCER; PHASE-II AB Background: There have been few evaluations of the risk of acute nonlymphocytic leukemia (ANLL) following therapy for non-Hodgkin's lymphoma (NHL). Further, the relationship between cumulative dose of cytotoxic drug, radiation dose to active bone marrow, and the risk of ANLL following NHL have not been well described. Purpose: Our purpose was to examine the risk of ANLL in relationship to all prior treatment for NHL. Methods: Within a cohort study of 11 386 2-year survivors of NHL, 35 case patients with secondary ANLL were identified and matched to 140 controls with NHL who did not develop ANLL. The primary eligibility criteria for the cohort included a diagnosis of NHL as a first primary cancer from January 1, 1965, through December 31, 1989; age 18 through 70 years at the time of initial diagnosis; and survival for 2 or more years without the development of a second invasive primary malignancy. Detailed information on chemotherapeutic drugs and radiotherapy was collected for all patients. Standard conditional logistic regression programs were used to estimate the relative risk (RR) of ANLL associated with specific therapies by comparing the exposure histories of case patients with individually matched controls. Results: Significant excesses of ANLL followed therapy with either prednimustine (RR = 13.4; 95% confidence interval [CI] = 1.1-156; P trend for dose <.05) or regimens containing mechlorethamine and procarbazine (RR = 12.6; 95% CI = 2.0-79; P<.05). Elevated risks of leukemia following therapy with chlorambucil were restricted to patients given cumulative doses of 1300 mg or more (RR = 6.5; 95% CI = 1.6-26; P<.05), Cyclophosphamide regimens were associated with a small, nonsignificant increased risk of ANLL (RR = 1.8; 95% CI = 0.7-4.9), with most patients receiving relatively low cumulative doses (<20 000 mg). Radiotherapy given at higher doses without alkylating agents was linked to a nonsignificant threefold risk of ANLL compared with lower dose radiation or no radiotherapy. Conclusions: Our results suggest that prednimustine may be a human carcinogen, with a positive dose-response gradient evident for ANLL risk. The low, nonsignificant risk of leukemia associated with cyclophosphamide was reassuring because this drug is commonly used today. Despite the excesses of ANLL associated with specific therapies, secondary leukemia remains a rare occurrence following NHL. Of 10 000 NHL patients treated for 6 months with selected regimens including low cumulative doses of cyclophosphamide and followed for 10 years, an excess of four leukemias might be expected. C1 UNIV TEXAS, MD ANDERSON CANC CTR, HOUSTON, TX USA. ONTARIO CANC TREATMENT & RES FDN, TORONTO, ON, CANADA. NETHERLANDS CANC INST, AMSTERDAM, NETHERLANDS. UNIV UPPSALA HOSP, UPPSALA, SWEDEN. UNIV IOWA, IOWA CITY, IA USA. DR DANIEL DEN HOED CANC CTR, 3008 AE ROTTERDAM, NETHERLANDS. MAYO CLIN & MAYO FDN, ROCHESTER, MN 55905 USA. UNIV TEXAS, HLTH SCI CTR, SAN ANTONIO, TX USA. PRINCESS MARGARET HOSP, TORONTO M4X 1K9, ON, CANADA. RP TRAVIS, LB (reprint author), NCI, DIV CANC ETIOL, EPIDEMIOL & BIOSTAT PROGRAM, EXECUT PLAZA N, SUITE 408, BETHESDA, MD 20892 USA. RI Tucker, Margaret/B-4297-2015 NR 56 TC 78 Z9 79 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD OCT 5 PY 1994 VL 86 IS 19 BP 1450 EP 1457 DI 10.1093/jnci/86.19.1450 PG 8 WC Oncology SC Oncology GA PJ101 UT WOS:A1994PJ10100008 PM 8089863 ER PT J AU VUISTER, GW KIM, SJ WU, C BAX, A AF VUISTER, GW KIM, SJ WU, C BAX, A TI 2D AND 3D NMR-STUDY OF PHENYLALANINE RESIDUES IN PROTEINS BY REVERSE ISOTOPIC LABELING SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID J-COUPLINGS; STAPHYLOCOCCAL NUCLEASE; SECONDARY STRUCTURE; PEPTIDE COMPLEX; SPECTROSCOPY; SPECTRA; ASSIGNMENTS; RESONANCES; H-1-NMR; C-13 AB A protein isotopic labeling strategy is presented which offers improved NMR sensitivity and resolution relative to the commonly used uniform C-13 labeling approach. Incorporation of specific residues at natural abundance into an otherwise fully C-13-enriched protein yields H-1 line widths for the unlabeled residues which are not adversely affected by C-13 and makes it possible to selectively focus on interactions between the unlabeled residues and the remainder of the protein. Modifications of C-13 editing and C-12 filtering procedures are described which optimize their sensitivity and resolution. The experiments are used to obtain complete assignments for all 10 phenylalanine aromatic spin systems in the DNA-binding domain of Drosophila heat shock factor and to obtain a large number of structurally important long-range NOE constraints. A novel J correlation experiment is also described which makes it possible to measure H-alpha-H-beta J couplings in larger proteins and yields quantitative values for all 10 phenylalanines in the DNA-binding domain of Drosophila heat shock factor. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 35 TC 86 Z9 89 U1 2 U2 14 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 OCT 5 PY 1994 VL 116 IS 20 BP 9206 EP 9210 DI 10.1021/ja00099a041 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA PK979 UT WOS:A1994PK97900041 ER PT J AU GUSTAFSON, KR SOWDER, RC HENDERSON, LE PARSONS, IC KASHMAN, Y CARDELLINA, JH MCMAHON, JB BUCKHEIT, RW PANNELL, LK BOYD, MR AF GUSTAFSON, KR SOWDER, RC HENDERSON, LE PARSONS, IC KASHMAN, Y CARDELLINA, JH MCMAHON, JB BUCKHEIT, RW PANNELL, LK BOYD, MR TI CIRCULIN-A AND CIRCULIN-B - NOVEL HIV-INHIBITORY MACROCYCLIC PEPTIDES FROM THE TROPICAL TREE CHASSALIA-PARVIFOLIA SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Note ID DEFENSINS; ANALOGS; VIRUS; CELL C1 NCI,FREDERICK CANC RES & DEV CTR,DEV THERAPEUT PROGRAM,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702. NR 21 TC 209 Z9 214 U1 0 U2 9 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 OCT 5 PY 1994 VL 116 IS 20 BP 9337 EP 9338 DI 10.1021/ja00099a064 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA PK979 UT WOS:A1994PK97900064 ER PT J AU HORN, EP HARTGE, P SHIELDS, JA TUCKER, MA AF HORN, EP HARTGE, P SHIELDS, JA TUCKER, MA TI SUNLIGHT AND RISK OF UVEAL MELANOMA SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Note ID HOST FACTORS; EXPOSURE C1 HOWARD HUGHES MED INST,BETHESDA,MD 20817. NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. WILLS EYE HOSP & RES INST,ONCOL SERV,PHILADELPHIA,PA 19107. RI Tucker, Margaret/B-4297-2015 NR 11 TC 18 Z9 18 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 OCT 5 PY 1994 VL 86 IS 19 BP 1476 EP 1478 DI 10.1093/jnci/86.19.1476 PG 3 WC Oncology SC Oncology GA PJ101 UT WOS:A1994PJ10100013 PM 8089868 ER PT J AU EDWARDS, BK HANKEY, BF AF EDWARDS, BK HANKEY, BF TI AMENDED LONG-TERM TRENDS IN CANCER INCIDENCE RATES IN CHILDREN - REPLY SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI,DIV CANC PREVENT & CONTROL,SURVEILLANCE PROGRAM,BETHESDA,MD 20892. NR 1 TC 1 Z9 1 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 5 PY 1994 VL 86 IS 19 BP 1482 EP 1482 DI 10.1093/jnci/86.19.1482 PG 1 WC Oncology SC Oncology GA PJ101 UT WOS:A1994PJ10100015 ER PT J AU KEARSE, KP ROBERTS, JL MUNITZ, TI WIEST, DL NAKAYAMA, T SINGER, A AF KEARSE, KP ROBERTS, JL MUNITZ, TI WIEST, DL NAKAYAMA, T SINGER, A TI DEVELOPMENTAL REGULATION OF ALPHA-BETA-T-CELL ANTIGEN RECEPTOR EXPRESSION RESULTS FROM DIFFERENTIAL STABILITY OF NASCENT TCR-ALPHA PROTEINS WITHIN THE ENDOPLASMIC-RETICULUM OF IMMATURE AND MATURE T-CELLS SO EMBO JOURNAL LA English DT Article DE ALLELIC EXCLUSION; T CELL DIFFERENTIATION; T CELL RECEPTOR ID PRE-GOLGI DEGRADATION; CD4+CD8+ THYMOCYTES; MONOCLONAL-ANTIBODY; NEGATIVE SELECTION; SURFACE EXPRESSION; RAPID DEGRADATION; CHAINS; COMPLEX; PURIFICATION; EVENTS AB The alpha beta T cell antigen receptor (TCR) that is expressed on most T lymphocytes is a multisubunit transmembrane complex composed of at least six different proteins (alpha, beta, gamma, delta, epsilon and zeta) that are assembled in the endoplasmic reticulum (ER) and then transported to the plasma membrane. Expression of the TCR complex is quantitatively regulated during T cell development, with immature CD4(+) CD8(+) thymocytes expressing only 10% of the number of surface alpha beta TCR complexes that are expressed on mature T cells. However, the molecular basis for low TCR expression in developing alpha beta T cells is unknown. In the present study we report the unexpected finding that assembly of nascent component chains into complete TCR alpha beta complexes is severely impaired in immature CD4(+) CD8(+) thymocytes relative to their mature T cell progeny. In particular, the initial association of TCR alpha with TCR beta proteins, which occurs relatively efficiently in mature T cells, is markedly inefficient in immature CD4(+) CD8(+) thymocytes, even for a matched pair of transgenic TCR alpha and TCR beta proteins. Inefficient formation of TCR alpha beta heterodimers in immature CD4(+)CD8(+) thymocytes was found to result from the unique instability of nascent TCR alpha proteins within the ER of immature CD4(+) CD8(+) thymocytes, with nascent TCR alpha proteins having a median survival time of only 15 min in CD4(+) CD8(+) thymocytes, but >75 min in mature T cells. Thus, these data demonstrate that stability of TCR alpha proteins within the ER is developmentally regulated and provide a molecular basis for quantitative differences in alpha beta TCR expression on immature and mature T cells. In addition, these results provide the first example of a receptor complex whose expression is quantitatively regulated during development by post-translational limitations on receptor assembly. RP KEARSE, KP (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,BETHESDA,MD 20892, USA. RI Nakayama, Toshinori/E-1067-2017; OI Wiest, David/0000-0002-0792-3188 NR 44 TC 68 Z9 69 U1 0 U2 1 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 OCT 3 PY 1994 VL 13 IS 19 BP 4504 EP 4514 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PL720 UT WOS:A1994PL72000008 PM 7925292 ER PT J AU SEGALL, AM GOODMAN, SD NASH, HA AF SEGALL, AM GOODMAN, SD NASH, HA TI ARCHITECTURAL ELEMENTS IN NUCLEOPROTEIN COMPLEXES - INTERCHANGEABILITY OF SPECIFIC AND NONSPECIFIC DNA-BINDING PROTEINS SO EMBO JOURNAL LA English DT Article DE HISTONES; HMG BOX; HU; IHF; PHAGE LAMBDA SITE-SPECIFIC RECOMBINATION ID SITE-SPECIFIC RECOMBINATION; INTEGRATION HOST FACTOR; HISTONE-LIKE PROTEIN; COLI IHF PROTEIN; ESCHERICHIA-COLI; BACTERIOPHAGE-LAMBDA; HU PROTEIN; GEL-ELECTROPHORESIS; ATTACHMENT SITES; PHAGE LAMBDA AB Integration host factor (IHF) is required in lambda site-specific recombination to deform the DNA substrates into conformations active for recombination. HU, a homolog of IHF, can also deform DNA but binds without any apparent sequence specificity. We demonstrate that HU can replace IHF by cooperating with the recombinase protein, integrase, to generate a stable and specific complex with electrophoretic mobility and biochemical activity very close to the complex formed by IHF and integrase. The eukaryotic HMG1 and HMG2 proteins differ entirely in structure from HU but they also bind DNA non-specifically and induce or stabilize deformed DNA. We show that the eukaryotic HMG1 and HMG2 proteins cooperate with integrase at least as well as does HU to make a defined structure. We also find that the eukaryotic core histone dimer H2A-H2B can replace IHF, suggesting that the histone dimer is functional outside the context of a nucleosome. HU and the HMG proteins not only contribute to the formation of stable complexes, but they can at least partially replace IHF for the integrative and excisive recombination reactions. These results, together with our analysis of nucleoprotein complexes made with damaged recombination sites, lead us to conclude that the cooperation between HU and integrase does not depend on protein-protein contacts. Rather, cooperation is manifested through building of higher order structures and depends on the capacity of the non-specific DNA binding proteins to bend DNA. While all these non-specific binding proteins appear to fulfil the same bending function, they do so with different efficiencies. This probably reflects subtle structural differences between the assembled complexes. C1 NIMH,MOLEC BIOL LAB,BETHESDA,MD 20892. RP SEGALL, AM (reprint author), SAN DIEGO STATE UNIV,DEPT BIOL,SAN DIEGO,CA 92182, USA. RI Goodman, Steven/C-5732-2013 NR 72 TC 122 Z9 122 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 OCT 3 PY 1994 VL 13 IS 19 BP 4536 EP 4548 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PL720 UT WOS:A1994PL72000011 PM 7925295 ER PT J AU KIEHNTOPF, M BRACH, MA LICHT, T PETSCHAUER, S KARAWAJEW, L KIRSCHNING, C HERRMANN, F AF KIEHNTOPF, M BRACH, MA LICHT, T PETSCHAUER, S KARAWAJEW, L KIRSCHNING, C HERRMANN, F TI RIBOZYME-MEDIATED CLEAVAGE OF THE MDR-1 TRANSCRIPT RESTORES CHEMOSENSITIVITY IN PREVIOUSLY RESISTANT CANCER-CELLS SO EMBO JOURNAL LA English DT Article DE CHEMOSENSITIVITY; MDR-1; RIBOZYME ID OVERCOMING MULTIDRUG RESISTANCE; MULTIPLE-DRUG RESISTANCE; MESSENGER-RNA; P-GLYCOPROTEIN; MONOCLONAL-ANTIBODY; GENE-EXPRESSION; ENZYMES; INVITRO; ALPHA; DNA AB How cancer cells become resistant to chemotherapy is not completely understood, but it is believed that resistance is usually associated with overexpression of drug resistance genes. Drug resistance mediated by the MDR-1 gene is the first well characterized form of drug resistance in human cancer. MDR-1 encodes a phosphoglycoprotein, P-GP, that serves as an energy-dependent drug efflux pump, reducing intracellular drug accumulation and thereby cytotoxicity. We have used ribozymes to reverse the multiple drug resistance phenotype. A hammerhead ribozyme recognizing the GUC sequence at position -6 to -4 close to the translation start site of the 4.5 kb MDR-1 mRNA was prepared by in vitro transcription (MDR-1-RZiv) or chemical synthesis (MDR-1-RZs). Both MDR-1-RZiv and MDR-1-RZs specifically cleaved the MDR-1 mRNA into two parts of the expected size under physiological conditions in an extracellular system with MDR-1-RZiv being more effective. Site-specific cleavage was dependent on time, temperature and [MgCl2]. To examine the in vivo potential of MDR-1-RZ, MDR-1-RZiv and MDR-1-RZs were transfected into a human pleural mesothelioma cell line and into one adriamycin-resistant and one vindesine-resistant subline thereof by liposome-mediated transfer. Incorporation of ribozymes resulted in significantly reduced expression of the MDR-1 gene, with MDR-1-RZs being more potent than MDR-1-RZiv in vitro. MDR-1-RZ reduces P-GP overexpression at the protein level. Liposome-mediated transfer of MDR-1-RZiv or MDR-1-RZs reversed the multiple drug resistance phenotype and restored sensitivity towards chemotherapeutic drugs. C1 FREE UNIV BERLIN,KLINIKUM RUDOLF VIRCHOW,ROBERT ROSSLE CANC CTR,DEPT MED ONCOL & APPL MOLEC BIOL,W-1000 BERLIN,GERMANY. MAX DELBRUCK CTR MOLEC MED,BERLIN,GERMANY. NCI,DCBDC,MOLEC BIOL LAB,BETHESDA,MD. NR 42 TC 65 Z9 66 U1 1 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD OCT 3 PY 1994 VL 13 IS 19 BP 4645 EP 4652 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PL720 UT WOS:A1994PL72000023 PM 7925305 ER PT J AU IZENWASSER, S TERRY, P HELLER, B WITKIN, JM KATZ, JL AF IZENWASSER, S TERRY, P HELLER, B WITKIN, JM KATZ, JL TI DIFFERENTIAL RELATIONSHIPS AMONG DOPAMINE TRANSPORTER AFFINITIES AND STIMULANT POTENCIES OF VARIOUS UPTAKE INHIBITORS SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE DOPAMINE UPTAKE; COCAINE; DOPAMINE TRANSPORTER ID NONHUMAN-PRIMATES; NUCLEUS-ACCUMBENS; COCAINE RECEPTORS; RAT STRIATUM; INVIVO; BINDING; LOCOMOTOR; BEHAVIOR; GBR-12909; COMPLEX AB Binding to the dopamine transporter and inhibiting dopamine reuptake are considered important factors in regulating behavioral effects of cocaine. One prominent behavioral effect of cocaine and other dopamine uptake inhibitors is the stimulation of locomotor activity. To examine the relationship between action at the dopamine transporter and behavior, the displacement of [H-3]WIN 35,428 (CFT naphthalene sulfate; 2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane-1,5-naphthalene disulfonate) binding in rat caudate putamen by cocaine and other uptake inhibitors was compared with stimulation of mouse locomotor activity. There was a significant correlation among affinities for binding and potencies for stimulating activity for cocaine and structurally similar compounds. For structurally dissimilar uptake inhibitors, however, there was no significant correlation among potencies for stimulation of activity and affinity for displacement of [H-3]WIN 35,428 binding. These findings provide evidence that cocaine analogs may bind to the dopamine transporter in a manner that is fundamentally different from that for structurally dissimilar uptake inhibitors. C1 UNIV BIRMINGHAM,SCH PSYCHOL,BIRMINGHAM B15 2TT,W MIDLANDS,ENGLAND. RP IZENWASSER, S (reprint author), NATL INST DRUG ABUSE,INTRAMURAL RES PROGRAM,PSYCHOL SECT,POB 5180,BALTIMORE,MD 21224, USA. RI Izenwasser, Sari/G-9193-2012; OI Katz, Jonathan/0000-0002-1068-1159 NR 33 TC 64 Z9 64 U1 2 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 OCT 3 PY 1994 VL 263 IS 3 BP 277 EP 283 DI 10.1016/0014-2999(94)90723-4 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PK726 UT WOS:A1994PK72600007 PM 7843265 ER PT J AU SHIMADA, A SPANGLER, EL LONDON, ED INGRAM, DK AF SHIMADA, A SPANGLER, EL LONDON, ED INGRAM, DK TI SPERMIDINE POTENTIATES DIZOCILPINE-INDUCED IMPAIRMENT OF LEARNING-PERFORMANCE BY RATS IN A 14-UNIT T-MAZE SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE GLUTAMATE RECEPTOR; POLYAMINE; MEMORY; ION CHANNEL ID METHYL-D-ASPARTATE; LONG-TERM POTENTIATION; ANTICONVULSANT MK-801; HIPPOCAMPAL-NEURONS; REGIONAL DISTRIBUTION; ENHANCES PERFORMANCE; CHANNEL COMPLEX; D-CYCLOSERINE; CELL-DEATH; RECEPTOR AB The NMDA receptor, a ligand-gated ion channel complex, has been reported to be involved in memory processes. Learning is impaired following administration of dizocilpine, a non-competitive antagonist of the NMDA receptor. Polyamines, such as spermine and spermidine, interact with the NMDA receptor to enhance binding of dizocilpine, which blocks the ion channel. The present study assessed action of polyamines as modulators of learning via NMDA receptor activation. Dizocilpine (0.05 mg/kg) was given i.p. before maze learning, at a dose that produced a slight, nonsignificant impairment of maze learning. Pretreatment with 80 mg/kg but not 15 or 40 mg/kg spermidine (i.p.) before dizocilpine impaired maze learning compared to saline controls. Administration of 80 mg/kg spermidine without dizocilpine did not impair maze learning. The results are consistent with the view that systemic injection of a polyamine can modulate learning processes involving the NMDA receptor. C1 NIA, GERONTOL RES CTR, MOLEC PHYSIOL & GENET SECT, NATHAN W SHOCK LABS, BALTIMORE, MD 21224 USA. NIDA, ADDICT RES CTR, PSYCHOBIOL LAB, NEUROIMAGING & DRUG ACT SECT, BALTIMORE, MD 21224 USA. NR 44 TC 21 Z9 21 U1 3 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 EI 1879-0712 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD OCT 3 PY 1994 VL 263 IS 3 BP 293 EP 300 DI 10.1016/0014-2999(94)90725-0 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PK726 UT WOS:A1994PK72600009 PM 7843267 ER PT J AU DAWSON, DA AF DAWSON, DA TI HEAVY DRINKING AND THE RISK OF OCCUPATIONAL INJURY SO ACCIDENT ANALYSIS AND PREVENTION LA English DT Article DE ALCOHOL CONSUMPTION; WORK INJURY ID ACCIDENTAL FALLS; ALCOHOL; SMOKING; DEATH; PREVENTION; STATES AB This study evaluated the association between the frequency of heavy drinking and the risk of occupational injury, using nationally representative data from the 1988 National Health Interview Survey (NHIS). The sample consisted of 29,192 adults who were employed at some time during the year preceding the NHIS interview. Overall, 7.2% reported an on-the-job injury during the preceding year, but the rates were higher-about 13%-for those employed as skilled or unskilled laborers or who reported engaging in repeated strenuous physical activity at work. Slightly more than one-fourth of the employed adults reported at least one occasion of drinking five or more drinks during the preceding year. After adjusting for the effects of age, gender, education, occupation, and strenuous job activity, the odds of occupational injury increased with frequency of heavy drinking, with odds ratios varying from 1.08 (one occasion of heavy drinking) to 1.74 (daily heavy drinking). Odds ratios were decreased slightly by the inclusion of smoking as a control variable, indicating that some of the excess risk of injury among heavy drinkers may reflect their greater propensity to take health-related risks rather than direct effects of ethanol, The odds ratios also were slightly lower when the analysis was restricted to current drinkers, suggesting that the risk of work injury was increased by light or moderate as well as heavy drinking. RP DAWSON, DA (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,6000 EXECUT BLVD,SUITE 514,ROCKVILLE,MD 20892, USA. NR 28 TC 43 Z9 43 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0001-4575 J9 ACCIDENT ANAL PREV JI Accid. Anal. Prev. PD OCT PY 1994 VL 26 IS 5 BP 655 EP 665 DI 10.1016/0001-4575(94)90027-2 PG 11 WC Ergonomics; Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary; Transportation SC Engineering; Public, Environmental & Occupational Health; Social Sciences - Other Topics; Transportation GA PF001 UT WOS:A1994PF00100011 PM 7999210 ER PT J AU GURALNIK, JM WINOGRAD, CH AF GURALNIK, JM WINOGRAD, CH TI PHYSICAL PERFORMANCE-MEASURES IN THE ASSESSMENT OF OLDER PERSONS SO AGING-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Editorial Material RP GURALNIK, JM (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,7201 WINSCONSIN AVE,GATEWAY BLDG,ROOM 3C-309,BETHESDA,MD 20892, USA. NR 0 TC 30 Z9 32 U1 0 U2 8 PU EDITRICE KURTIS S R L PI MILANO PA VIA LUIGI ZOJA, 30-20153 MILANO, ITALY SN 0394-9532 J9 AGING-CLIN EXP RES JI Aging-Clin. Exp. Res. PD OCT PY 1994 VL 6 IS 5 BP 303 EP 305 PG 3 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA PQ103 UT WOS:A1994PQ10300001 PM 7893776 ER PT J AU CLERICI, M CLARK, EA POLACINO, P AXBERG, I KULLER, L CASEY, NI MORTON, WR SHEARER, GM BENVENISTE, RE AF CLERICI, M CLARK, EA POLACINO, P AXBERG, I KULLER, L CASEY, NI MORTON, WR SHEARER, GM BENVENISTE, RE TI T-CELL PROLIFERATION TO SUBINFECTIOUS SIV CORRELATES WITH LACK OF INFECTION AFTER CHALLENGE OF MACAQUES SO AIDS LA English DT Article DE SIV; CELL-MEDIATED IMMUNE RESPONSE; AIDS VACCINES; INTRARECTAL VIRUS INOCULATION; MUCOSAL INFECTION; T LYMPHOCYTES; SYNTHETIC PEPTIDES ID SIMIAN IMMUNODEFICIENCY VIRUS; ENVELOPE GLYCOPROTEIN; MACACA-FASCICULARIS; HIV; MONKEYS; VACCINES; DISEASE; TRANSMISSION; PATHOGENESIS; INDIVIDUALS AB Objectives: To analyze correlates of protection in macaques exposed to SIV. Methods: Peripheral blood mononuclear cells (PBMC) from macaques inoculated intrarectally with various dilutions of SIV were examined for their in vitro proliferative response to SIV envelope peptides and generation of SIV-specific antibodies. Some macaques previously exposed intravenously to subinfectious doses of SIV were subsequently challenged 16 months later with an infectious intrarectal dose of SIV. Results: The viral-specific immune responses of macaques exposed to infectious doses of SIV were characterized by generation of antibodies and weak or undetectable T-cell-mediated responses. In contrast, macaques inoculated with doses of SIV below the threshold required for seroconversion and recovery of virus exhibited T-cell proliferation in response to SIV envelope synthetic peptides. The macaques that had previously been exposed to SIV resisted the subsequent virus challenge, whereas the naive macaques (never exposed to SIV) all became infected. Conclusions: The inability to productively infect macaques previously exposed to subinfectious doses of SIV suggests that a T-cell-mediated response may confer long-term protection against infection, and that AIDS vaccines should be designed to optimize the cellular arm of the immune response. C1 NCI,EXPTL IMMUNOL BRANCH,FREDERICK,MD 21702. UNIV WASHINGTON,REG PRIMATE RES CTR,SEATTLE,WA. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD. RI Clark, Edward/K-3462-2012 FU NCRR NIH HHS [RR00166] NR 28 TC 103 Z9 103 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD OCT PY 1994 VL 8 IS 10 BP 1391 EP 1395 DI 10.1097/00002030-199410000-00004 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PH418 UT WOS:A1994PH41800004 PM 7818809 ER PT J AU WEISSMAN, D POLI, G FAUCI, AS AF WEISSMAN, D POLI, G FAUCI, AS TI INTERLEUKIN-10 BLOCKS HIV REPLICATION IN MACROPHAGES BY INHIBITING THE AUTOCRINE LOOP OF TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-6 INDUCTION OF VIRUS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; GROWTH-FACTOR-BETA; T-CELL CLONES; PRIMARY MONONUCLEAR PHAGOCYTES; KERATINOCYTE-DERIVED IL-10; DIFFERENTIATION FACTOR; CYTOKINE PRODUCTION; INFECTED MONOCYTES; PROMONOCYTIC CELLS; IFN-ALPHA AB Human interleukin 10 is a pleiotropic cytokine capable of suppressing cytokine production from macrophages and T cells; in addition, it exerts complex regulatory effects on CD8(+) T cells, natural killer cells, vascular endothelial cells, and B lymphocytes. Levels of IL-10 are elevated in HIV-infected individuals, suggesting that this cytokine may play a role in the suppression of T cell and monocyte/macrophage function typical of HIV disease. In this article, IL-10 blocked HIV-induced tumor necrosis factor alpha and interleukin 6 secretion and inhibited HIV replication in monocyte-derived macrophages (MDMs). The inhibition by IL-10 was correlated with a block in endogenous TNF-alpha and IL-6 secretion from HIV-infected MDMs. RP WEISSMAN, D (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 6A02,BETHESDA,MD 20892, USA. NR 47 TC 127 Z9 128 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 OCT PY 1994 VL 10 IS 10 BP 1199 EP 1206 DI 10.1089/aid.1994.10.1199 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PP910 UT WOS:A1994PP91000002 PM 7848677 ER PT J AU ATWOOD, WJ TORNATORE, CS TRAUB, R CONANT, K DREW, PD MAJOR, EO AF ATWOOD, WJ TORNATORE, CS TRAUB, R CONANT, K DREW, PD MAJOR, EO TI STIMULATION OF HIV TYPE-1 GENE-EXPRESSION AND INDUCTION OF NF-KAPPA-B (P50/P65)-BINDING ACTIVITY IN TUMOR NECROSIS FACTOR-ALPHA-TREATED HUMAN FETAL GLIAL-CELLS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS DEMENTIA COMPLEX; T-CELLS; HUMAN POLYOMAVIRUS; MICROGLIAL CELLS; BINDING-PROTEINS; NERVOUS-SYSTEM; III INFECTION; BRAIN-TISSUE; ENCEPHALOPATHY AB In vitro, HIV-1 infection of human fetal glial cells initiates a noncytopathic, productive infection that results in a long-term persistence during which the viral genome remains latent. The cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) reactivate HIV-1 gene expression in these cells, leading to production of infectious virus. Here we show that treatment of human fetal glial cells with TNF-alpha and IL-1 beta increase expression of the reporter gene chloramphenicol acetyltransferase (CAT) when placed under the control of the HIV-1 5' LTR. We also show that treatment of human fetal glial cells with TNF-alpha leads to increased binding of the nuclear transcription factor NF-kappa B (p50/p65) to a consensus kappa B-binding site present in the HIV-1 5' LTR. Our results suggest that TNF-alpha stimulation of HIV-1 gene expression in primary cultures of human fetal glial cells is mediated by an increase in binding of NF-kappa B (p50/p65) to the HIV-1 LTR. This is the first report documenting NF-kappa B-binding activity in primary cultures of human fetal glial cells. C1 NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. RP ATWOOD, WJ (reprint author), NINCDS,MOLEC MED & NEUROSCI LAB,BLDG 36-5D04,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 42 TC 33 Z9 34 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 OCT PY 1994 VL 10 IS 10 BP 1207 EP 1211 DI 10.1089/aid.1994.10.1207 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PP910 UT WOS:A1994PP91000003 PM 7848678 ER PT J AU VASLIN, B CLAVERIE, JM BENVENISTE, O BARRESINOUSSI, FC DORMONT, D AF VASLIN, B CLAVERIE, JM BENVENISTE, O BARRESINOUSSI, FC DORMONT, D TI NEF AND GAG SYNTHETIC PEPTIDE PRIMING OF ANTIBODY-RESPONSES TO HIV TYPE-1 ANTIGENS IN MICE AND PRIMATES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RECOMBINANT VACCINIA VIRUS; CYTOTOXIC LYMPHOCYTE-T; SEROPOSITIVE INDIVIDUALS; ENVELOPE GLYCOPROTEIN; CONFERS PROTECTION; IMMUNE-RESPONSE; VIRAL ENVELOPE; CELL EPITOPES; PROTEIN AB T epitope mapping in human immunodeficiency virus proteins provides a useful tool for AIDS vaccine design. We have previously shown that four peptides selected from the Gag polyprotein of HIV-1 were able to prime mice for in vitro lymphoproliferative responses. These responses were shown to be MHC restricted, and a pool of these peptides was able to prime mice for a subsequent humoral response to HIV-1 Gag proteins. Here we show that two of these Gag peptides are able to prime the anti-HIV-1 IgG response to heat-inactivated HIV-1 in B10Sc.Cr mice. Furthermore, we extended this study in the nonhuman primate model, and show efficient priming of the IgG response to heat-inactivated HIV-1 using the pool of four Gag peptides in baboons. Further mapping of ''nonself' peptides is extended to the HIV-1 Nef protein. Three potential Nef T epitopes located at positions 137-145, 98-107, and 81-95 are also shown to prime the IgG response to HIV-1 in the mouse model, although T cell proliferation to recall peptides' in vitro was not detectable. Although they have not yet been defined as major helper T epitopes in humans, using classic in vitro stimulation assays, the fact that most of them are able to prime IgG responses in animals without detectable in vitro proliferative responses does not rule out their functional helper capacity in humans. C1 CEA,DAV,DPTE,NEUROPATHOL EXPTL & NEUROVIROL LAB,SERV SANTE ARMEES,CTR RECH,F-92265 FONTENAY ROSES,FRANCE. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. INST PASTEUR,UNITE BIOL RETROVIRUS,F-75015 PARIS,FRANCE. RI Barre-Sinoussi, Francoise/G-8355-2011 NR 45 TC 5 Z9 5 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 OCT PY 1994 VL 10 IS 10 BP 1241 EP 1250 DI 10.1089/aid.1994.10.1241 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PP910 UT WOS:A1994PP91000007 PM 7531460 ER PT J AU MILMAN, G SHARMA, O AF MILMAN, G SHARMA, O TI MECHANISMS OF HIV/SIV MUCOSAL TRANSMISSION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; PRIMARY HIV-1 INFECTION; SEXUAL TRANSMISSION; LYMPHOCYTE SUBSETS; LANGERHANS CELLS; RHESUS MACAQUES; DISEASE STAGE; GENITAL-TRACT; TYPE-1 AB The Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases (NIAID), organized a Workshop on HIV/SIV Pathogenesis and Mucosal Transmission on March 14-17, 1994, attended by over 300 participants. The purpose of the workshop was to foster research in the areas of HIV pathogenesis, mucosal transmission, and host factors modulating HIV infection and disease. This article summarizes workshop presentations that focused on mechanisms of HIV or SIV mucosal transmission. The following are highlights from the workshop. The epidemiological data indicating a low probability of infection from a single sexual exposure are consistent with observations that infectious cell-free or cell-associated HIV could be isolated from only 10-57 % of semen samples, and that high levels of SIV are required for infection by a mucosal route. Several lines of circumstantial evidence suggest that an important property of a transmitted HIV or SIV is the ability to infect macrophages. A potential mechanism for cell-associated mucosal transmission is provided by the observations that CD4-negative epithelial cells in culture are efficiently infected by direct contact with HIV-infected T cells, and that HIV-infected epithelial cells are observed in vivo. Cell-free HIV virions contain partial reverse transcripts of viral RNA into DNA, and conditions that promote DNA reverse transcripts, such as incubation in seminal fluid, increase viral infectivity. Finally, evidence is accumulating that transient or abortive infection with short-term recovery of infectious virus in blood can occur in the absence of seroconversion. RP MILMAN, G (reprint author), NIAID,DIV AIDS,BETHESDA,MD 20892, USA. NR 52 TC 89 Z9 90 U1 1 U2 4 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 OCT PY 1994 VL 10 IS 10 BP 1305 EP 1312 DI 10.1089/aid.1994.10.1305 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PP910 UT WOS:A1994PP91000014 PM 7848686 ER PT J AU ZAKHARI, S ALTURA, BM AF ZAKHARI, S ALTURA, BM TI ALCOHOL AND MAGNESIUM - INTRODUCTION TO THE SYMPOSIUM SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Editorial Material ID HYPERTENSION; EXCRETION; RAT C1 SUNY HLTH SCI CTR,DEPT MED,BROOKLYN,NY 11203. SUNY HLTH SCI CTR,DEPT PHYSIOL,BROOKLYN,NY 11203. RP ZAKHARI, S (reprint author), NIAAA,DIV BASIC RES,BIOMED RES BRANCH,WILLCO BLDG,6000 EXECUT BLVD,ROCKVILLE,MD 20892, USA. NR 33 TC 0 Z9 0 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD OCT PY 1994 VL 18 IS 5 BP 1037 EP 1039 DI 10.1111/j.1530-0277.1994.tb00080.x PG 3 WC Substance Abuse SC Substance Abuse GA PP457 UT WOS:A1994PP45700002 PM 7847585 ER PT J AU VEECH, RL GATES, DN CRUTCHFIELD, C GITOMER, WL KASHIWAYA, Y KING, MT WONDERGEM, R AF VEECH, RL GATES, DN CRUTCHFIELD, C GITOMER, WL KASHIWAYA, Y KING, MT WONDERGEM, R TI METABOLIC HYPERPOLARIZATION OF LIVER BY ETHANOL - THE IMPORTANCE OF MG2+ AND H+ IN DETERMINING IMPERMEANT INTRACELLULAR ANIONIC CHARGE AND ENERGY OF METABOLIC REACTIONS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article ID FREE MAGNESIUM; RAT-LIVER; P-31 NMR; SKELETAL-MUSCLE; ION CONCENTRATION; HEART; SPECTROSCOPY; HEPATOCYTES; PH; THERMODYNAMICS C1 E TENNESSEE STATE UNIV,QUILLEN DISHNER COLL MED,DEPT PHYSIOL,JOHNSON CITY,TN 37614. RP VEECH, RL (reprint author), NIAAA,METAB & MOLEC BIOL LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. FU NIAAA NIH HHS [AA-08867] NR 68 TC 15 Z9 15 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD OCT PY 1994 VL 18 IS 5 BP 1040 EP 1056 DI 10.1111/j.1530-0277.1994.tb00081.x PG 17 WC Substance Abuse SC Substance Abuse GA PP457 UT WOS:A1994PP45700003 PM 7531402 ER PT J AU DOMANSKI, MJ TOPOL, EJ AF DOMANSKI, MJ TOPOL, EJ TI CARDIOGENIC-SHOCK - CURRENT UNDERSTANDINGS AND FUTURE-RESEARCH DIRECTIONS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material ID ACUTE MYOCARDIAL-INFARCTION; AORTIC BALLOON COUNTERPULSATION; TISSUE PLASMINOGEN-ACTIVATOR; CARDIOPULMONARY BYPASS SUPPORT; LUMINAL CORONARY ANGIOPLASTY; LEFT-VENTRICULAR FUNCTION; THROMBOLYTIC THERAPY; IMPROVES SURVIVAL; REPERFUSION; MORTALITY C1 CLEVELAND CLIN FDN,DEPT CARDIOL,CLEVELAND,OH 44195. CLEVELAND CLIN FDN,CTR THROMBOSIS & VASC BIOL,CLEVELAND,OH. RP DOMANSKI, MJ (reprint author), NHLBI,CLIN TRIALS BRANCH,BLDG 10,BETHESDA,MD 20892, USA. OI Topol, Eric/0000-0002-1478-4729 NR 56 TC 14 Z9 18 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 OCT 1 PY 1994 VL 74 IS 7 BP 724 EP 726 DI 10.1016/0002-9149(94)90318-2 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PH142 UT WOS:A1994PH14200017 PM 7942534 ER PT J AU GUINEE, DG FISHBACK, NF KOSS, MN ABBONDANZO, SL TRAVIS, WD AF GUINEE, DG FISHBACK, NF KOSS, MN ABBONDANZO, SL TRAVIS, WD TI THE SPECTRUM OF IMMUNOHISTOCHEMICAL STAINING OF SMALL-CELL LUNG-CARCINOMA IN SPECIMENS FROM TRANSBRONCHIAL AND OPEN-LUNG BIOPSIES SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE BER-EP4; BOMBESIN; CARCINOEMBRYONIC ANTIGEN; CHROMOGRANIN A; IMMUNOHISTOCHEMISTRY; KERATIN; NEURON-SPECIFIC ENOLASE; LEU-7; SMALL-CELL LUNG CARCINOMA ID NEURON-SPECIFIC ENOLASE; MONOCLONAL-ANTIBODY HNK-1; NATURAL-KILLER CELLS; NEUROENDOCRINE TUMORS; SOMATOSTATIN ANALOG; ANTIGENIC DETERMINANT; SURFACE GLYCOPROTEIN; ENDOCRINE NEOPLASMS; MR 34,000; CANCER AB Immunohistochemistry is increasingly used as an aid in the diagnosis of small-cell lung carcinoma (SCLC). Previous studies have investigated immunohistochemical staining of SCLC with small numbers of antibodies, but few have examined large series with a broad panel of antibodies. For this reason, the authors examined the distribution and intensity of staining of 20 open-lung biopsy (OLB) and 21 transbronchial biopsy (TBB) specimens of SCLC with a panel of epithelial, neuroendocrine, and hormonal markers. Small-cell lung carcinoma stained most frequently with epithelial markers, followed by neuroendocrine and hormonal markers. Similar percentages of OLB and TBB specimens stained for keratin (100% each) and epithelial membrane antigen (100% and 95%, respectively). Unexpectedly, BER-EP4 stained 100% of OLB specimens. Chromogranin A was the most frequent neuroendocrine marker in OLB and TBB specimens (60% and 47%, respectively) followed by neuron-specific enolase (60% and 33%), Leu-7 (40% and 24%), and synaptophysin (5% and 19%). No neuroendocrine immunohistochemical reactivity was found in 24% of TBB specimens and 20% of OLB specimens. Bombesin was the most sensitive hormonal marker (45% of OLB specimens). These results show that keratin, epithelial membrane antigen, and BER-EP4 are reliable epithelial markers for SCLC in both TBB and OLB specimens. In addition, negative staining for neuroendocrine markers, because it can occur in as many as 25% of cases, should not deter the diagnosis of SCLC. C1 ARMED FORCES INST PATHOL,DEPT PULM & MEDIASTINAL PATHOL,WASHINGTON,DC 20306. ARMED FORCES INST PATHOL,DIV IMMUNOPATHOL,WASHINGTON,DC 20306. RP GUINEE, DG (reprint author), NCI,PATHOL LAB,BLDG 10,ROOM 2N212,BETHESDA,MD 20892, USA. NR 63 TC 82 Z9 83 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD OCT PY 1994 VL 102 IS 4 BP 406 EP 414 PG 9 WC Pathology SC Pathology GA PL836 UT WOS:A1994PL83600005 PM 7524299 ER PT J AU ZARATEOSORNO, A RAFFELD, M BERMAN, EL FERGUSON, MM ANDRADE, R JAFFE, ES AF ZARATEOSORNO, A RAFFELD, M BERMAN, EL FERGUSON, MM ANDRADE, R JAFFE, ES TI S-100-POSITIVE T-CELL LYMPHOPROLIFERATIVE DISORDER - A CASE-REPORT AND REVIEW OF THE LITERATURE SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Note DE T-CELL, LEUKEMIA; S-100 PROTEIN; T-CELL LYMPHOMA ID HUMAN LYMPHOCYTES-T; S-100 PROTEIN; LEUKEMIA; LYMPHOMA; FEATURES; TISSUES; DISEASE; SUBSET AB The authors describe a patient with a S-100-positive T-cell lymphoproliferative disorder, characterized by clinically aggressive behavior, with leukemic dissemination and death within 1 year of the onset of symptoms. The neoplastic cells had abundant amphophilic cytoplasm, suggestive of plasmacytoid differentiation, but demonstrated a mature T-cell immunophenotype characteristic of the suppressor-cytotoxic subset. In addition, the cells expressed the S-100 protein within the cytoplasm. Genotypic studies were performed by Southern blot analysis, which demonstrated beta-chain T-cell receptor gene rearrangement, further confirming the T-cell nature of this disorder. This case had features very similar to those of the seven cases previously reported. It has been proposed that the S-100-positive T-cell lymphoproliferative disorder is a distinctive clinicopathologic entity. C1 NCI,PATHOL LAB,HEMATOPATHOL SECT,BETHESDA,MD 20892. ST BARNABAS HOSP,DEPT PATHOL,LIVINGSTON,NJ. NR 24 TC 13 Z9 13 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD OCT PY 1994 VL 102 IS 4 BP 478 EP 482 PG 5 WC Pathology SC Pathology GA PL836 UT WOS:A1994PL83600017 PM 7942605 ER PT J AU HATCH, EE BRACKEN, MB AF HATCH, EE BRACKEN, MB TI ASSOCIATION OF DELAYED CONCEPTION WITH CAFFEINE CONSUMPTION - REPLY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter ID PREGNANCY C1 YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06520. RP HATCH, EE (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,ROCKVILLE,MD 20852, USA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 1994 VL 140 IS 7 BP 664 EP 665 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PK213 UT WOS:A1994PK21300015 ER PT J AU LEWIS, CE FUNKHOUSER, E HILNER, JE BRAGG, C RACZYNSKI, JM CAAN, B ARMSTRONG, MA FRIEDMAN, GD DYER, A SAVAGE, PJ AF LEWIS, CE FUNKHOUSER, E HILNER, JE BRAGG, C RACZYNSKI, JM CAAN, B ARMSTRONG, MA FRIEDMAN, GD DYER, A SAVAGE, PJ TI INCONSISTENT ASSOCIATIONS OF CAFFEINE-CONTAINING BEVERAGES WITH BLOOD-PRESSURE AND WITH LIPOPROTEINS - THE CARDIA STUDY - REPLY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 KAISER PERMANENTE MED CARE PROGRAM,DIV RES,OAKLAND,CA 94611. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL 60611. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. RP LEWIS, CE (reprint author), UNIV ALABAMA,DEPT MED,DIV PREVENT MED,BIRMINGHAM,AL 35294, USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 1994 VL 140 IS 7 BP 666 EP 667 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PK213 UT WOS:A1994PK21300017 ER PT J AU BRIGGS, MD CHOI, HC WARMAN, ML LOUGHLIN, JA WORDSWORTH, P SYKES, BC IRVEN, CMM SMITH, M WYNNEDAVIES, R LIPSON, MH BIESECKER, LG GARBER, AP LACHMAN, R OLSEN, BR RIMOIN, DL COHN, DH AF BRIGGS, MD CHOI, HC WARMAN, ML LOUGHLIN, JA WORDSWORTH, P SYKES, BC IRVEN, CMM SMITH, M WYNNEDAVIES, R LIPSON, MH BIESECKER, LG GARBER, AP LACHMAN, R OLSEN, BR RIMOIN, DL COHN, DH TI GENETIC-MAPPING OF A LOCUS FOR MULTIPLE EPIPHYSEAL DYSPLASIA (EDM2) TO A REGION OF CHROMOSOME-I CONTAINING A TYPE IX COLLAGEN GENE SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID LINKAGE MAP; L-MYC; CARTILAGE; PSEUDOACHONDROPLASIA; RECOMBINATION; LOCALIZATION; PROTEOGLYCAN; AGGRECAN; CLONING AB Multiple epiphyseal dysplasia (MED) is a dominantly inherited chondrodysplasia characterized by mild short stature and early-onset osteoarthrosis. Some forms of MED clinically resemble another chondrodysplasia phenotype, the mild form of pseudoachondroplasia (PSACH). On the basis of their clinical similarities as well as similar ultrastructural and biochemical features in cartilage from some patients, it has been proposed that MED and PSACH belong to a single bone-dysplasia family. Recently, both mild and severe PSACH as well as a form of MED have been linked to the same interval on chromosome 19, suggesting that they may be allelic disorders. Linkage studies with the chromosome 19 markers were carried out in a large family with MED and excluded the previously identified interval. Using this family, we have identified an MED locus on the short arm of chromosome 1, in a region containing the gene (COL9A2) that encodes the alpha 2 chain of type IX collagen, a structural component of the cartilage extracellular matrix. C1 CEDARS SINAI MED CTR,DEPT OBSTET & GYNECOL,LOS ANGELES,CA 90048. STEVEN SPIELBERG PEDIAT RES CTR,AHMANSON DEPT PEDIAT,LOS ANGELES,CA 90048. UNIV CALIF LOS ANGELES,SCH MED,DEPT RADIOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PEDIAT,LOS ANGELES,CA 90024. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. UNIV OXFORD,INST MOLEC MED,OXFORD,ENGLAND. JOHN RADCLIFFE HOSP,NUFFIELD DEPT CLIN MED,OXFORD OX3 9DU,ENGLAND. ST THOMAS HOSP,DEPT ORTHOPAED SURG,LONDON,ENGLAND. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. PERMANENTE MED GRP INC,SACRAMENTO,CA. FU NIAMS NIH HHS [AR36820, AR36819]; NICHD NIH HHS [HD22657] NR 39 TC 70 Z9 70 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 OCT PY 1994 VL 55 IS 4 BP 678 EP 684 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA PJ027 UT WOS:A1994PJ02700010 PM 7942845 ER PT J AU LALWANI, AK BRISTER, JR FEX, J GRUNDFAST, KM PIKUS, AT PLOPLIS, B SANAGUSTIN, T SKARKA, H WILCOX, ER AF LALWANI, AK BRISTER, JR FEX, J GRUNDFAST, KM PIKUS, AT PLOPLIS, B SANAGUSTIN, T SKARKA, H WILCOX, ER TI NEW NONSYNDROMIC X-LINKED SENSORINEURAL HEARING IMPAIRMENT LINKED TO XP21.2 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DUCHENNE MUSCULAR-DYSTROPHY; CONGENITAL ADRENAL HYPOPLASIA; MENTAL-RETARDATION; DMD GENE; INTRAGENIC RECOMBINATION; LINKAGE ANALYSIS; HIGH-FREQUENCY; DEAFNESS; DEFICIENCY; DELETIONS AB X-linked deafness is a rare cause of hereditary hearing impairment. We have identified a family with X-linked dominant sensorineural hearing impairment, characterized by incomplete penetrance and variable expressivity in carrier females, that is linked to the Xp21.2, which contains the Duchenne muscular dystrophy (DMD) locus. The auditory impairment in affected males was congenital, bilateral, profound, sensorineural, affecting all frequencies, and without evidence of radiographic abnormality of the temporal bone. Adult carrier females manifested bilateral, mild-to-moderate high-frequency sensorineural hearing impairment of delayed onset during adulthood. Eighteen commercially available polymorphic markers from the X chromosome, generating a 10-15-cM map, were initially used for identification of a candidate region. DXS997, located within the DMD gene, generated a two-point LOD score of 2.91 at theta = 0, with every carrier mother heterozygous at this locus. Recombination events at DXS332 (located within the DMD locus, 3' to exon 50 of the dystrophin gene) and at DXS1068 (5' to the brain promoter of the dystrophin gene) were observed. No recombination events were noted with the following markers within the DMD locus: 5'DYS II, intron 44, DXS997, and intron 50. There was no clinical evidence of Duchenne or Becker muscular dystrophy in any family member. It is likely that this family represents a new locus on the X chromosome, which when mutated results in nonsyndromic sensorineural hearing loss and is distinct from the heterogeneous group of X-linked hearing losses that have been previously described. C1 NIDCD,PUBL HLTH SERV,GENET MOLEC LAB,BETHESDA,MD 20892. NR 57 TC 39 Z9 43 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 OCT PY 1994 VL 55 IS 4 BP 685 EP 694 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA PJ027 UT WOS:A1994PJ02700011 PM 7942846 ER PT J AU FARRER, LA ARNOS, KS ASHER, JH BALDWIN, CT DIEHL, SR FRIEDMAN, TB GREENBERG, J GRUNDFAST, KM HOTH, C LALWANI, AK LANDA, B LEVERTON, K MILUNSKY, A MORELL, R NANCE, WE NEWTON, V RAMESAR, R RAO, VS REYNOLDS, JE SANAGUSTIN, TB WILCOX, ER WINSHIP, I READ, AP AF FARRER, LA ARNOS, KS ASHER, JH BALDWIN, CT DIEHL, SR FRIEDMAN, TB GREENBERG, J GRUNDFAST, KM HOTH, C LALWANI, AK LANDA, B LEVERTON, K MILUNSKY, A MORELL, R NANCE, WE NEWTON, V RAMESAR, R RAO, VS REYNOLDS, JE SANAGUSTIN, TB WILCOX, ER WINSHIP, I READ, AP TI LOCUS HETEROGENEITY FOR WAARDENBURG SYNDROME IS PREDICTIVE OF CLINICAL SUBTYPES SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SYNDROME TYPE-I; FAMILIAL ALZHEIMERS-DISEASE; PLACENTAL ALKALINE-PHOSPHATASE; HUP2 PAIRED DOMAIN; PAX3 GENE; DINUCLEOTIDE REPEAT; FRAMESHIFT MUTATION; HUMAN HOMOLOG; MOUSE; SPLOTCH AB Waardenburg syndrome (WS) is a dominantly inherited and clinically variable syndrome of deafness, pigmentary changes, and distinctive facial features. Clinically, WS type I(WS1) is differentiated from WS type II (WS2) by the high frequency of dystopia canthorum in the family. In some families, WS is caused by mutations in the PAX3 gene on chromosome 2q. We have typed microsatellite markers within and flanking PAX3 in 41 WS1 kindreds and 26 WS2 kindreds in order to estimate the proportion of families with probable mutations in PAX3 and to study the relationship between phenotypic and genotypic heterogeneity. Evaluation of heterogeneity in location scores obtained by multilocus analysis indicated that WS is linked to PAX3 in 60% of all WS families and in 100% of WS1 families. None of the WS2 families were linked. In those families in which equivocal lod scores (between -2 and +1) were found, PAX3 mutations have been identified in 5 of the 15 WS1 families but in none of the 4 WS2 families. Although preliminary studies do not suggest any association between the phenotype and the molecular pathology in 20 families with known PAX3 mutations and in four patients with chromosomal abnormalities in the vicinity of PAX3, the presence of dystopia in multiple family members is a reliable indicator for identifying families likely to have a defect in PAX3. C1 BOSTON UNIV,SCH MED,DEPT BIOSTAT & EPIDEMIOL,BOSTON,MA 02118. BOSTON UNIV,SCH MED,CTR HUMAN GENET,BOSTON,MA 02118. GALLAUDET UNIV,WASHINGTON,DC 20002. MICHIGAN STATE UNIV,DEPT ZOOL,E LANSING,MI 48824. MICHIGAN STATE UNIV,GRAD PROGRAM GENET,E LANSING,MI 48824. NIDR,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,MOLEC EPIDEMIOL & DIS INDICATORS BRANCH,BETHESDA,MD 20892. NIDOCD,MOLEC OTOL LAB,BETHESDA,MD. UNIV CAPE TOWN,DEPT HUMAN GENET,CAPE TOWN 7925,SOUTH AFRICA. VIRGINIA COMMONWEALTH UNIV,DEPT HUMAN GENET,RICHMOND,VA. UNIV MANCHESTER,DEPT MED GENET,MANCHESTER,LANCS,ENGLAND. UNIV MANCHESTER,CTR AUDIOL,MANCHESTER,LANCS,ENGLAND. RP FARRER, LA (reprint author), BOSTON UNIV,SCH MED,DEPT NEUROL,80 E CONCORD ST,BOSTON,MA 02118, USA. RI Ramesar, Raj/I-6941-2015; OI Ramesar, Raj/0000-0001-5688-1634; Morell, Robert/0000-0003-1537-7356; Farrer, Lindsay/0000-0001-5533-4225; Winship, Ingrid/0000-0001-8535-6003 FU NIDCD NIH HHS [DC-00038, DC-01160, DC-01848]; Wellcome Trust NR 59 TC 52 Z9 56 U1 0 U2 3 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 OCT PY 1994 VL 55 IS 4 BP 728 EP 737 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA PJ027 UT WOS:A1994PJ02700016 PM 7942851 ER PT J AU DEAN, M STEPHENS, JC WINKLER, C LOMB, DA RAMSBURG, M BOAZE, R STEWART, C CHARBONNEAU, L GOLDMAN, D ALBAUGH, BJ GOEDERT, JJ BEASLEY, RP HWANG, LY BUCHBINDER, S WEEDON, M JOHNSON, PA EICHELBERGER, M OBRIEN, SJ AF DEAN, M STEPHENS, JC WINKLER, C LOMB, DA RAMSBURG, M BOAZE, R STEWART, C CHARBONNEAU, L GOLDMAN, D ALBAUGH, BJ GOEDERT, JJ BEASLEY, RP HWANG, LY BUCHBINDER, S WEEDON, M JOHNSON, PA EICHELBERGER, M OBRIEN, SJ TI POLYMORPHIC ADMIXTURE TYPING IN HUMAN ETHNIC POPULATIONS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID AMERINDIAN MITOCHONDRIAL DNAS; HUMAN GENOME PROJECT; HUMAN-EVOLUTION; LINKAGE MAP; VIRUS; AIDS; RECOMBINATION; SEQUENCES; DIVERSITY; REPEAT AB A panel of 257 RFLP loci was selected on the basis of high heterozygosity in Caucasian DNA surveys and equivalent spacing throughout the human genome. Probes from each locus were used in a Southern blot survey of allele frequency distribution for four human ethnic groups: Caucasian, African American, Asian (Chinese), and American Indian (Cheyenne). Nearly all RFLP loci were polymorphic in each group, albeit with a broad range of differing allele frequencies (delta). The distribution of frequency differences (delta values) was used for three purposes: (1) to provide estimates for genetic distance (differentiation) among these ethnic groups, (2) to revisit with a large data set the proportion of human genetic variation attributable to differentiation within ethnic groups, and (3) to identify loci with high delta values between recently admired populations of use in mapping by admixture linkage disequilibrium (MALD). Although most markers display significant allele frequency differences between ethnic groups, the overall genetic distances between ethnic groups were small(.066-.098), and <10% of the measured overall molecular genetic diversity in these human samples can be attributed to ''racial'' differentiation. The median 6 values for pairwise comparisons between groups fell between .15 and .20, permitting identification of highly informative RFLP loci for MALD disease association studies. C1 NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. NIAAA,CLIN STUDIES LAB,BETHESDA,MD 20892. INST BEHAV RES,CLINTON,OK. UNIV TEXAS,HLTH SCI CTR,SCH PUBL HLTH,HOUSTON,TX. DEPT PUBL HLTH,SAN FRANCISCO CITY CLIN,SAN FRANCISCO,CA. RI Dean, Michael/G-8172-2012; Goldman, David/F-9772-2010 OI Dean, Michael/0000-0003-2234-0631; Goldman, David/0000-0002-1724-5405 NR 43 TC 74 Z9 75 U1 1 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1994 VL 55 IS 4 BP 788 EP 808 PG 21 WC Genetics & Heredity SC Genetics & Heredity GA PJ027 UT WOS:A1994PJ02700022 PM 7942857 ER PT J AU STEPHENS, JC BRISCOE, D OBRIEN, SJ AF STEPHENS, JC BRISCOE, D OBRIEN, SJ TI MAPPING BY ADMIXTURE LINKAGE DISEQUILIBRIUM IN HUMAN-POPULATIONS - LIMITS AND GUIDELINES SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENE; POLYMORPHISMS; LOCI AB Certain human hereditary conditions, notably those with low penetrance and those which require an environmental event such as infectious disease exposure, are difficult to localize in pedigree analysis, because of uncertainty in the phenotype of an affected patient's relatives. An approach to locating these genes in human cohort studies would be to use association analysis, which depends on linkage disequilibrium of flanking polymorphic DNA markers. In theory, a high degree of linkage disequilibrium between genes separated by 10-20 cM will be generated and persist in populations that have a history of recent (3-20 generations ago) admixture between genetically differentiated racial groups, such as has occurred in African Americans and Hispanic populations. We have conducted analytic and computer simulations to quantify the effect of genetic, genomic, and population parameters that affect the amount and ascertainment of linkage disequilibrium in populations with a history of genetic admixture. Our goal is to thoroughly explore the ranges of all relevant parameters or factors (e.g., sample size and degree of genetic differentiation between populations) that may be involved in gene localization studies, in hopes of prescribing guidelines for an efficient mapping strategy. The results provide reasonable limits on sample size (200-300 patients), marker number (200-300 in 20-cM intervals), and allele differentiation (loci with allele frequency difference of greater than or equal to .3 between admired parent populations) to produce an efficient approach (>95% ascertainment) for locating genes not easily tracked in human pedigrees. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 32 TC 166 Z9 171 U1 1 U2 4 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 OCT PY 1994 VL 55 IS 4 BP 809 EP 824 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA PJ027 UT WOS:A1994PJ02700023 PM 7942858 ER PT J AU DEMENT, JM BROWN, DP OKUN, A AF DEMENT, JM BROWN, DP OKUN, A TI FOLLOW-UP-STUDY OF CHRYSOTILE ASBESTOS TEXTILE WORKERS - COHORT MORTALITY AND CASE-CONTROL ANALYSES SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article ID OCCUPATIONAL EPIDEMIOLOGY; DUST EXPOSURE; CONDUCT; DESIGN AB Previous studies of mortality among white males employed in a Charleston, South Carolina asbestos textile plant using chrysotile demonstrated significant excess mortality due to asbestos-related disease and a steep exposure-response relationship for lung cancer. This cohort was further studied by adding 15 years of follow-up and including mortality among white female and black male workers. Nested case-control analyses were undertaken to further explore possible differences in lung cancer risk by textile operation as well as possible confounding by mineral oil exposures. Preliminary data for white males have been previously published. White males experienced statistically significant excess mortality due to lung cancer (standardized mortality ratio [SMR] = 2.30; confidence interval [CI] = 1.88-2.79), all causes (SMR = 1.48; CI = 1.38-1.58), all cancers (SMR = 1.50; CI = 1.29-1.72), diabetes mellitus (SMR = 2.05; CI = 1.18-3.33), heart disease (SMR = 1.41; CI = 1.26-1.58), cerebrovascular disease (SMR = 1.50; CI = 1.08-2.02), pneumoconiosis and other respiratory diseases (SMR = 4.10; CI = 3.10-5.31), and accidents (SMR = 1.49; CI = 1.15-1.91). Among white females, statistically significant excesses occurred for lung cancer (SMR = 2.75; CI = 2.06-3.61), all causes (SMR = 1.21; CI = 1.11-1.32), pneumoconiosis and other respiratory diseases (SMR = 2.40; CI = 1.53-3.60), and other respiratory cancers (SMR = 14.98; CI = 4.08-38.7). Among the total cohort of black males, the only statistically significant excess observed was for pneumoconiosis (SMR = 2.19; CI = 1.23-3.62). Based on historical exposure measurements at the plant, there was a postive exposure-response relationship for both lung cancer and pneumoconiosis. Data for the entire cohort demonstrate an increase in the lung cancer relative risk of 2-3% for each fiber/cc-year of cumulative chrysotile exposure. This relationship was more consistent for the white male workers. The excess risk for lung cancer among white males and females appeared to occur at cumulative exposures lower than those for black males. Possible reasons for the lesser lung cancer risk among black male include less smoking and differences in airborne fiber characteristics experienced by black males as a result of plant job placement patterns. The case-control analysis found employment in preparation and carding operations (where most of the black males worked) to be associated with a slightly reduced lung cancer risk, although not statistically significant, whereas spinning and twisting employment was associated with a statistically significant increased lung cancer risk compared to other plant operations. Airborne fiber size data, determined by transmission electron microscopy, demonstrated slightly longer fibers in spinning and twisting compared to other textile operations. Case-control analyses demonstrated little effect of mineral oil exposures on the lung cancer exposure-response estimates. Two deaths due to mesothelioma were observed among this cohort. (C) 1994 Wiley-Liss, Inc.* C1 NIEHS,OFF DIS PREVENT,RES TRIANGLE PK,NC 27709. RP DEMENT, JM (reprint author), DUKE UNIV,MED CTR,DIV OCCUPAT & ENVIRONM MED,BOX 2914,2200 W MAIN ST,SUITE 700,DURHAM,NC 27710, USA. NR 34 TC 92 Z9 96 U1 2 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD OCT PY 1994 VL 26 IS 4 BP 431 EP 447 DI 10.1002/ajim.4700260402 PG 17 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PH354 UT WOS:A1994PH35400001 PM 7810543 ER PT J AU CHOW, WH MCLAUGHLIN, JK MALKER, HSR WEINER, JA ERICSSON, JLE STONE, BJ BLOT, WJ AF CHOW, WH MCLAUGHLIN, JK MALKER, HSR WEINER, JA ERICSSON, JLE STONE, BJ BLOT, WJ TI OCCUPATION AND STOMACH-CANCER IN A COHORT OF SWEDISH MEN SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE OCCUPATION; STOMACH CANCER; SWEDEN; CANCER REGISTRY DATA ID GASTRIC-CANCER; JEWELRY WORKERS; MORTALITY; ETIOLOGY; MINERS; DEATH; RISKS; ADENOCARCINOMA; MESOTHELIOMA; ASSOCIATIONS AB Using the Cancer-Environment Registry of Sweden, which links the 1960 census information on employment with cancer incidence data from 1961-1979, we conducted a systematic, population-based assessment of stomach cancer incidence by industry and occupation for men in Sweden. Nearly 17,000 stomach cancer cases were diagnosed during the 19 years of follow-up. Stomach cancer incidence was elevated among miners and quarrymen, farmers and fishermen, and craftsmen and production workers. Men who held white collar jobs, including professional and technical, administrative and management, clerical, and sales jobs, had a reduction in stomach cancer incidence. Examination of specific jobs revealed generally elevated rates of stomach cancer among men who may be exposed to dusty work environments, such as quarry workers, stone cutters, circular and plane operators, construction workers, crane operators, heavy laborers, and shop and construction metal workers. These occupational associations mostly were observed for stomach cancers of noncardia origin, and no significant associations were found with cardia cancers. We had no information on dietary or other potential confounding factors and cannot make inferences about the role of occupation per se, but the current findings support those of earlier investigations and add to the evidence of a small but significant occupational role in stomach carcinogenesis. (C) 1994 Wiley-Liss, Inc. C1 NATL BOARD OCCUPAT SAFETY & HLTH,S-17184 SOLNA,SWEDEN. NATL BOARD HLTH & WELF,STOCKHOLM,SWEDEN. RP CHOW, WH (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 43 TC 25 Z9 25 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 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD OCT PY 1994 VL 26 IS 4 BP 511 EP 520 DI 10.1002/ajim.4700260408 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PH354 UT WOS:A1994PH35400007 PM 7810549 ER PT J AU INFANTE, PF SCHUMAN, LD DEMENT, J HUFF, J AF INFANTE, PF SCHUMAN, LD DEMENT, J HUFF, J TI FIBROUS GLASS AND CANCER SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Note DE FIBROUS GLASS; GLASS FIBERS; CARCINOGENICITY; OCCUPATIONAL STUDIES; NATIONAL-TECHNOLOGY-PROGRAM; EXPERIMENTAL EXPOSURES; ANNUAL REPORT ON CARCINOGENS; IARC DEFINITIONS ID MINERAL FIBER WORKERS; MADE VITREOUS FIBERS; FOLLOW-UP; LUNG-CANCER; CARCINOGENICITY; RATS; MORTALITY; INHALATION; DIMENSION; ASBESTOS AB Some argue that fibrous glass (glass wool) should not be considered as a likely human carcinogen and hence should not be listed in the Seventh Annual Report on Carcinogens (ARC) prepared by the National Toxicology Program (NTP) and mandated by the U.S. Congress. In examining this issue, data from both laboratory experiments (animal studies) and epidemiologic studies (human data) are reviewed with the results evaluated according to the criteria established by the International Agency for Research on Cancer (IARC) and adopted in slightly modified form by the NTP for classifying substances as human carcinogens or likely human carcinogens. From our comprehensive review of the available information, we conclude that fibrous glass materials are carcinogenic, and in view of the NTP and IARC definitions should be listed in the ARC. Our review then examines the carcinogenic potency of glass fibers to humans in comparison with asbestos fibers and concludes that on a fiber-per-fiber basis, glass fibers may be as potent or even more potent than asbestos. The implications of these findings are then presented for regulatory purposes in the occupational setting. (C) 1994 Wiley-Liss, Inc.* C1 NIEHS,ENVIRONM CARCINOGENESIS PROGRAM,RES TRIANGLE PK,NC 27709. DUKE UNIV,MED CTR,DIV OCCUPAT & ENVIRONM MED,DURHAM,NC 27710. RP INFANTE, PF (reprint author), US OCCUPAT SAFETY & HLTH ADM,HLTH STAND PROGRAM,WASHINGTON,DC 20210, USA. NR 47 TC 41 Z9 41 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD OCT PY 1994 VL 26 IS 4 BP 559 EP 584 DI 10.1002/ajim.4700260413 PG 26 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PH354 UT WOS:A1994PH35400012 PM 7810554 ER PT J AU PARRY, DM ELDRIDGE, R KAISERKUPFER, MI BOUZAS, EA PIKUS, A PATRONAS, N AF PARRY, DM ELDRIDGE, R KAISERKUPFER, MI BOUZAS, EA PIKUS, A PATRONAS, N TI NEUROFIBROMATOSIS 2 (NF2) - CLINICAL CHARACTERISTICS OF 63 AFFECTED INDIVIDUALS AND CLINICAL-EVIDENCE FOR HETEROGENEITY SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE NEUROFIBROMATOSIS 2; VESTIBULAR SCHWANNOMAS; MENINGIOMAS; CATARACTS; RETINAL HAMARTOMAS; MAGNETIC RESONANCE IMAGING; GADOLINIUM; HETEROGENEITY ID BILATERAL ACOUSTIC NEUROFIBROMATOSIS; LENS OPACITIES; VONRECKLINGHAUSEN NEUROFIBROMATOSIS; TYPE-2 NEUROFIBROMATOSIS; RETINAL HAMARTOMAS; TUMOR-SUPPRESSOR; FOLLOW-UP; GENE; CHROMOSOME-22; ASSOCIATION AB To determine the spectrum of manifestations in neurofibromatosis 2 (NF2) and to assess possible heterogeneity, we evaluated 63 affected individuals from 32 families. Work-up included skin and neurologic examinations, audiometry, a complete ophthalmology examination with slit-lamp biomicroscopy of the lens and fundus, and gadolinium-enhanced MRI of the brain and, in some, of the spine. Mean age-at-onset in 58 individuals was 20.3 years; initial symptoms resulted from vestibular schwannomas (44.4%), other CNS tumors (22.2%), skin tumors (12.7%), and ocular manifestations including cataracts and retinal hamartomas (12.7%). Five asymptomatic individuals were diagnosed through screening. Vestibular schwannomas were documented in 62 individuals (98.4%); other findings included cataracts (81.0%), skin tumors (67.7%), spinal tumors (67.4%), and meningiomas (49.2%). Usually, clinical manifestations and course were similar within families but differed among families. To assess possible heterogeneity, we assigned affected individuals to three proposed subtypes (representing mild, intermediate, and severe NF2) based on age at-onset, presence or absence of CNS tumors other than vestibular schwannomas, and presence or absence of retinal hamartomas. Comparisons among the three subtypes for many clinical parameters demonstrated that patients in the mild subtype differed from those in the other two subtypes for most parameters, but that none of the parameters distinguished patients in the intermediate subtype from those in the severe subtype. Thus, there are likely two rather than three subtypes of NF2. Classification of patients to subtype may aid in counseling about long-term prognosis and in formulating individualized guidelines for medical surveillance. (C) 1994 Wiley-Liss, Inc. C1 NEI, OPHTHALM GENET & CLIN SERV BRANCH, BETHESDA, MD 20892 USA. NIDOCD, NEUROOTOL BRANCH, CLIN OTOL UNIT, BETHESDA, MD USA. NIH, CTR CLIN, DEPT DIAGNOST RADIOL, BETHESDA, MD 20892 USA. US PHS, BETHESDA, MD USA. RP PARRY, DM (reprint author), NCI, CLIN EPIDEMIOL BRANCH, EXECUT PLAZA N, ROOM 400, BETHESDA, MD 20892 USA. FU NCI NIH HHS [N01-CP-15602, N01-CP-61012] NR 49 TC 234 Z9 239 U1 2 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-7299 EI 1096-8628 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 1 PY 1994 VL 52 IS 4 BP 450 EP 461 DI 10.1002/ajmg.1320520411 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA PH660 UT WOS:A1994PH66000010 PM 7747758 ER PT J AU BRYAN, RN MANOLIO, TA SCHERTZ, LD JUNGREIS, C POIRIER, VC ELSTER, AD KRONMAL, RA AF BRYAN, RN MANOLIO, TA SCHERTZ, LD JUNGREIS, C POIRIER, VC ELSTER, AD KRONMAL, RA TI A METHOD FOR USING MR TO EVALUATE THE EFFECTS OF CARDIOVASCULAR-DISEASE ON THE BRAIN - THE CARDIOVASCULAR HEALTH STUDY SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article DE HEART; BRAIN DISEASES; BRAIN, INFARCTION; BRAIN, MAGNETIC RESONANCE; MAGNETIC RESONANCE, COMPARATIVE STUDIES ID WHITE-MATTER LESIONS; MAGNETIC-RESONANCE; ALZHEIMERS-DISEASE; ELDERLY SUBJECTS; AGING BRAIN; CT; TOMOGRAPHY; DEMENTIA; FOCI AB PURPOSE: To do a pilot study for the Cardiovascular Health Study (a population-based, longitudinal study of coronary heart disease and stroke in adults 65 years of age and older designed to identify risk factors related to cerebrovascular disease, particularly stroke): (a) to determine the feasibility of adding brain MR to the full-scale study; (b) to evaluate the reliability of standardized MR image interpretation in a multicenter study; and (c) to compare the prevalence of stroke determined by MR with that by clinical history. METHODS: Protocol-defined MR studies were performed in 100 subjects with clinical histories of stroke and 203 subjects without reported histories of stroke. MR scans were independently evaluated by two trained neuroradiologists for the presence of small (less than or equal to 3 mm) and large (>3 mm) ''infarctlike'' lesions. The sizes of the cerebral sulci and lateral ventricles and the extent of white matter disease were graded on a scale of 0 to 9. RESULTS: Eighty percent of the Cardiovascular Health Study participants who were invited to undergo MR studies agreed to do so; 95% of those agreeing to the procedure successfully completed the exams. Intrareader and interreader reliability of infarctlike lesion identification was high for large lesions (kappa, 0.71 and 0.78, respectively) but not for small lesions (kappa, 0.71 and 0.32, respectively). Relaxed intrareader and interreader kappa scores for sulcal and ventricular sizes and extent of white matter disease were greater than 0.8. MR evidence of infarctlike lesions was present in 77% of the participants with histories of stroke but was also present in 23% of the participants without clinical histories of stroke. Seventy-nine percent of the infarctlike lesions were larger than 3 mm. CONCLUSIONS: This preliminary study indicates that a large, prospective, epidemiologic study of elderly subjects using MR scans of the brain for identification of cerebrovascular disease is feasible and that the interpretative results are reproducible, and suggests that MR evidence of stroke is more prevalent than reported clinical history of stroke. C1 NHLBI,BETHESDA,MD. PRESBYTERIAN UNIV HOSP,PITTSBURGH,PA. UNIV CALIF DAVIS,SACRAMENTO,CA. BOWMAN GRAY SCH MED,WINSTON SALEM,NC. CARDIOVASC HLTH STUDY COORDINATING CTR,SEATTLE,WA. RP BRYAN, RN (reprint author), JOHNS HOPKINS MED INST,600 N WOLFE ST,BALTIMORE,MD 21287, USA. RI Bryan, R. Nick/P-1661-2014 FU NHLBI NIH HHS [N01-HC-15103] NR 22 TC 168 Z9 169 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD OCT PY 1994 VL 15 IS 9 BP 1625 EP 1633 PG 9 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA PL564 UT WOS:A1994PL56400006 PM 7847205 ER PT J AU COULTRIP, LL LIEN, JM GOMEZ, R KAPERNICK, P KHOURY, A GROSSMAN, JH AF COULTRIP, LL LIEN, JM GOMEZ, R KAPERNICK, P KHOURY, A GROSSMAN, JH TI THE VALUE OF AMNIOTIC-FLUID INTERLEUKIN-6 DETERMINATION IN PATIENTS WITH PRETERM LABOR AND INTACT MEMBRANES IN THE DETECTION OF MICROBIAL INVASION OF THE AMNIOTIC CAVITY SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 14th Annual Meeting of the Society-of-Perinatal-Obstetricians CY JAN 24-29, 1994 CL LAS VEGAS, NV SP SOC PERINATAL OBSTETRICIANS DE INTERLEUKIN-6; CHORIOAMNIONITIS; GLUCOSE; GRAM STAIN; LEUKOCYTE ESTERASE; LIMULUS AMEBOCYTE LYSATE ASSAY ID INTRAAMNIOTIC INFECTION; HISTOLOGIC CHORIOAMNIONITIS; GRAM STAIN; CYTOKINES; GLUCOSE; BIOSYNTHESIS; INTRAPARTUM; DIAGNOSIS; ESTERASE; CELLS AB OBJECTIVES: Our purpose was to (1) determine the value of amniotic fluid interleukin-6 determination in the detection of microbial invasion of the amniotic cavity and (2) compare interleukin-6 to other rapid tests in the evaluation of preterm labor. STUDY DESIGN: Amniotic fluid interleukin-6 was determined quantitatively by enzyme-linked immunosorbent assay in 91 amniotic fluid specimens obtained by amniocentesis in 89 patients with preterm labor. Amniotic fluid cultures for aerobes, anaerobes, and mycoplasma species were performed. Receiver-operator characteristic curve analysis, logistic regression analysis, and Cox's proportional-hazards model were used to explore the relationship between several explanatory and outcome variables. Diagnostic index values of interleukin-6, glucose level, Gram stain, leukocyte esterase, and limulus amebocyte lysate assay for prediction of a positive amniotic fluid culture, preterm delivery, clinical infection, and neonatal sepsis were calculated. RESULTS: The prevalence of positive amniotic fluid cultures was 13% (12/89). The median interleukin-6 concentration in patients with positive cultures was 241.8 ng/ml, in contrast to 0.291 ng/ml in patients with negative cultures (p. < 0.005). Sensitivity and specificity of an interleukin-6 level greater than or equal to 6.17 ng/ml was 75% and 79%, in contrast to that of glucose, less than or equal to 12 mg/dl (83% and 86%) for a positive amniotic fluid culture and sensitivity (p = 0.26, z test). All patients with an interleukin-6 level > 6.17 ng/ml were delivered preterm, in contrast to 85.2% of patients with a glucose level less than or equal to 12 mg/dl. When all rapid tests and clinical parameters were considered simultaneously in the logistic model, only interleukin-6 maintained a significant relationship to preterm birth (odds ratio 35, p = 0.003). Cox's proportional analysis demonstrated a strong relationship between interleukin-6 and the amniocentesis-to-delivery interval after clinical variables were controlled for (hazard ratio 3.01, p < 0.00001). CONCLUSION: Amniotic fluid interleukin-6 determination may be a useful adjunct to our armamentarium of rapid tests to exclude infection and predict delivery in patients with preterm labor and intact membranes. C1 GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. NIH,PERINATOL BRANCH,BETHESDA,MD 20892. HENNEPIN CTY MED CTR,MINNEAPOLIS,MN. RP COULTRIP, LL (reprint author), FAIRFAX HOSP,FALLS CHURCH,VA 22046, USA. NR 25 TC 76 Z9 77 U1 0 U2 1 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 OCT PY 1994 VL 171 IS 4 BP 901 EP 911 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA PN360 UT WOS:A1994PN36000004 PM 7943100 ER PT J AU ROMERO, R GOMEZ, R GALASSO, M MAZOR, M BERRY, SM QUINTERO, RA COTTON, DB AF ROMERO, R GOMEZ, R GALASSO, M MAZOR, M BERRY, SM QUINTERO, RA COTTON, DB TI THE NATURAL INTERLEUKIN-1 RECEPTOR ANTAGONIST IN THE FETAL, MATERNAL, AND AMNIOTIC-FLUID COMPARTMENTS - THE EFFECT OF GESTATIONAL-AGE, FETAL GENDER, AND INTRAUTERINE INFECTION SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 14th Annual Meeting of the Society-of-Perinatal-Obstetricians CY JAN 24-29, 1994 CL LAS VEGAS, NV SP SOC PERINATAL OBSTETRICIANS DE INTERLEUKIN-1 RECEPTOR ANTAGONIST; INTRAAMNIOTIC INFECTION; PARTURITION; FETAL GENDER ID TUMOR-NECROSIS-FACTOR; PRETERM PARTURITION; PROSTAGLANDIN BIOSYNTHESIS; FACTOR-ALPHA; LABOR; TERM; CELLS; EXPRESSION; DELIVERY; RABBIT AB OBJECTIVES: The interleukin-1 receptor antagonist is a newly discovered cytokine that blocks the biologic effects of interleukin-1 in vitro and in vivo. This cytokine is a physiologic component of amniotic fluid and is considered to be of critical importance in the homeostasis of the cytokine network. This study was undertaken to systematically examine the bioavailability of interleukin-1 receptor antagonist in the maternal, fetal, and amniotic fluid compartments during term and preterm parturition in women with and without microbial invasion of the amniotic cavity. STUDY DESIGN: The patient population consisted of (1) pregnant women in the midtrimester (n = 42), (2) patients who underwent cordocentesis for diagnostic purposes (n = 39), (3) patients with preterm labor (n = 126), (4) women with term gestation (n = 102), and (5) healthy nonpregnant women (n = 8). Amniotic fluid was cultured for aerobic and anaerobic bacteria, as well as Mycoplasma sp. Interleukin-1 receptor antagonist concentrations were determined by enzyme-linked immunoassay in maternal and fetal plasma, amniotic fluid, and neonatal urine. Microbial invasion of the amniotic cavity was defined as the presence of a positive amniotic fluid culture for microorganisms. RESULTS: (1) Interleukin-1 receptor antagonist was normally present in fetal plasma samples obtained by cordocentesis, and its concentration increased with advancing gestational age (n = 39; r = 0.61, p < 0.001). (2) Patients at term not in labor had higher amniotic fluid interleukin-1 receptor antagonist concentrations than patients in the midtrimester (median 40.1 ng/ml, range 5.7 to 213.1 vs median 16.2 ng/ml, range 3.2 to 62.2, respectively, p < 0.001). (3) Amniotic fluid and cord plasma interleukin-1 receptor antagonist concentrations were significantly higher in patients with preterm labor and microbial invasion of the amniotic cavity than in those without microbial invasion of the amniotic cavity (amniotic fluid: median 219.9 ng/ml, range 35.4 to 504 vs median 80.6 ng/ml, range 24.3 to 399, respectively, p < 0.001; umbilical cord plasma: median 4.8 ng/ml, range 0.3 to 167.0 vs median 1.0 ng/ml, range 0 to 276.0, respectively, p < 0.05). In contrast, these differences were not found in patients with term labor either with or without microbial invasion of the amniotic cavity. (4) In both term and preterm patients the amniotic fluid and neonatal urine concentrations of interleukin-1 receptor antagonist were significantly higher in female fetuses than in male fetuses (amniotic fluid, preterm: median 191.9 ng/ml, range 51.6 to 504.0 vs median 61.1 ng/ml, range 11.5 to 284.9, respectively, p < 0.001; amniotic fluid, term: median 58.7 ng/ml, range 25.5 to 264.0 vs median 33.9 ng/ml, range 3.4 to 132.4, respectively, p < 0.001; neonatal urine: median 317 ng/ml, range 59.0 to 440.8 vs median 12.2 ng/ml, range 2.5 to 61.6, respectively, p < 0.005). CONCLUSIONS: (1) Interleukin-1 receptor antagonist is physiologically present in the fetal, maternal, and amniotic fluid compartments; (2) microbial invasion of the amniotic cavity in the preterm gestation is associated with a significant increase in the concentrations of this cytokine in the fetal and amniotic fluid compartments but not in maternal plasma; (3) fetal urine is a source of amniotic fluid interleukin-1 receptor antagonist; (4) fetal plasma interleukin-1 receptor antagonist concentrations increase with gestational age; (5) there is a significant effect of fetal gender in amniotic fluid and neonatal urine concentrations of interleukin-1 receptor antagonist. C1 NICHHD,PERINATOL RES BRANCH,BETHESDA,MD 20892. BEN GURION UNIV NEGEV,SOROKA MED CTR,IL-84105 BEER SHEVA,ISRAEL. RP ROMERO, R (reprint author), WAYNE STATE UNIV,HUTZEL HOSP,DEPT OBSTET & GYNECOL,4707 ST ANTOINE BLVD,DETROIT,MI 48201, USA. NR 25 TC 78 Z9 79 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 1994 VL 171 IS 4 BP 912 EP 921 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA PN360 UT WOS:A1994PN36000005 PM 7943101 ER PT J AU GOMEZ, R GALASSO, M ROMERO, R MAZOR, M SOROKIN, Y GONCALVES, L TREADWELL, M AF GOMEZ, R GALASSO, M ROMERO, R MAZOR, M SOROKIN, Y GONCALVES, L TREADWELL, M TI ULTRASONOGRAPHIC EXAMINATION OF THE UTERINE CERVIX IS BETTER THAN CERVICAL DIGITAL EXAMINATION AS A PREDICTOR OF THE LIKELIHOOD OF PREMATURE DELIVERY IN PATIENTS WITH PRETERM LABOR AND INTACT MEMBRANES SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 14th Annual Meeting of the Society-of-Perinatal-Obstetricians CY JAN 24-29, 1994 CL LAS VEGAS, NV SP SOC PERINATAL OBSTETRICIANS DE PRETERM LABOR; UTERINE CERVIX; ULTRASONOGRAPHY; PELVIC EXAMINATION ID LENGTH; RISK; BIRTH; EFFACEMENT; PROGRAM AB OBJECTIVE: The purpose of this study was to compare the diagnostic performance of ultrasonographic and digital examination of the cervix in the prediction of preterm delivery in patients presenting with preterm labor and intact membranes. STUDY DESIGN: Endovaginal ultrasonography was performed in 59 patients admitted with preterm labor (20 to 35 weeks) and cervical dilatation of < 3 cm. Cervical parameters evaluated included endocervical length, the presence of funneling, funnel length, funnel width, cervical index ([Funnel length + 1]/Endocervical length), and cervical dilatation and effacement as determined by digital examination. Outcome variables were the occurrence of preterm delivery (< 36 weeks) and the admission-to-delivery interval. RESULTS: The prevalence of preterm delivery was 37.3% (22/59). Receiver-operator characteristic curve and logistic regression analyses indicated a significant relationship between the occurrence of preterm delivery and ultrasonographic cervical parameters (p < 0.005 for each) but not with the results of digital examination of the cervix. Survival analysis demonstrated a shorter admission-to-deliver interval for patients with an abnormal cervical index or endocervical length (p < 0.005 for each). CONCLUSIONS: Endovaginal ultrasonographic examination of the uterine cervix is more accurate than digital examination of the cervix in the assessment of the risk for preterm delivery in patients with preterm labor and intact membranes. C1 WAYNE STATE UNIV,HUTZEL HOSP,DEPT OBSTET & GYNECOL,DETROIT,MI 48201. NICHHD,PERINATOL RES BRANCH,BETHESDA,MD 20892. NR 25 TC 172 Z9 181 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 1994 VL 171 IS 4 BP 956 EP 964 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA PN360 UT WOS:A1994PN36000014 PM 7943109 ER PT J AU SHERER, DM ABULAFIA, O AF SHERER, DM ABULAFIA, O TI DOPPLER AUDITORY-GUIDED SUBCLAVIAN VEIN CATHETERIZATION - AN ALTERNATIVE TO REAL-TIME ULTRASONOGRAPHICALLY GUIDED SUBCLAVIAN VEIN CATHETERIZATION - REPLY SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Letter C1 MARSHALL UNIV,SCH MED,DEPT OBSTET & GYNECOL,DIV GYNECOL ONCOL,HUNTINGTON,WV 25703. RP SHERER, DM (reprint author), GEORGETOWN UNIV,MED CTR,DEPT OBSTET & GYNECOL,NICHHD,DIV INTRAMURAL,PERINATOL RES BRANCH,3PHC,WASHINGTON,DC 20007, USA. NR 0 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 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 1994 VL 171 IS 4 BP 1164 EP 1165 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA PN360 UT WOS:A1994PN36000067 ER PT J AU CHEUNG, MK MARTIN, DF CHAN, CC CALLANAN, DG COWAN, CL NUSSENBLATT, RB AF CHEUNG, MK MARTIN, DF CHAN, CC CALLANAN, DG COWAN, CL NUSSENBLATT, RB TI DIAGNOSIS OF REACTIVE LYMPHOID HYPERPLASIA BY CHORIORETINAL BIOPSY SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID NEEDLE ASPIRATION BIOPSY AB We treated a patient with reactive lymphoid hyperplasia in whom the diagnosis was made by chorioretinal biopsy. Histopathologic examination and culture of the biopsied specimen allowed us to rule out a neoplastic or infectious process. The biopsy result allowed us to treat him with systemic corticosteroid alone, thus avoiding the potential harmful side effects of other medications, including antituberculous drugs. There were no surgical or postoperative complications. This study confirms the usefulness of chorioretinal biopsy for establishing a diagnosis and formulating a rational treatment plan. C1 GEORGETOWN UNIV,DEPT OPHTHALMOL,WASHINGTON,DC. RP CHEUNG, MK (reprint author), NEI,IMMUNOL LAB,BLDG 10,RM 10N202,9000 ROCKVILLE PIKE,MSC 1858,BETHESDA,MD 20892, USA. NR 15 TC 18 Z9 18 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD OCT PY 1994 VL 118 IS 4 BP 457 EP 462 PG 6 WC Ophthalmology SC Ophthalmology GA PK509 UT WOS:A1994PK50900006 PM 7943123 ER PT J AU SHIMAZAKI, J TSUBOTA, K FUKUSHIMA, Y HONDA, M AF SHIMAZAKI, J TSUBOTA, K FUKUSHIMA, Y HONDA, M TI DETECTION OF HEPATITIS-C VIRUS-RNA IN TEARS AND AQUEOUS-HUMOR SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Letter C1 NIH,AIDS RES CTR,IMMUNOL LAB,BETHESDA,MD. RP SHIMAZAKI, J (reprint author), TOKYO DENT COLL,DEPT OPHTHALMOL,5-11-13 SUGANO,ICHIKAWA,CHIBA 272,JAPAN. NR 5 TC 15 Z9 15 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD OCT PY 1994 VL 118 IS 4 BP 524 EP 525 PG 2 WC Ophthalmology SC Ophthalmology GA PK509 UT WOS:A1994PK50900017 PM 7943134 ER PT J AU DONOVAN, MJ HEMPSTEAD, B HUBER, LJ KAPLAN, D TSOULFAS, P CHAO, M PARADA, L SCHOFIELD, D AF DONOVAN, MJ HEMPSTEAD, B HUBER, LJ KAPLAN, D TSOULFAS, P CHAO, M PARADA, L SCHOFIELD, D TI IDENTIFICATION OF THE NEUROTROPHIN RECEPTORS P75 AND TRK IN A SERIES OF WILMS-TUMORS SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID AFFINITY NGF RECEPTOR; NERVE GROWTH-FACTOR; GENE-PRODUCT; FACTOR-II; NONNEURONAL TISSUES; EXPRESSION; COEXPRESSION; PROTEIN; CELLS; LOCALIZATION AB The molecular mechanisms underlying the pathogenesis of Wilms' tumor (WT) are poorly understood, although a variety of growth factors including platelet-derived growth factor and insulin like growth factor are expressed and are thought to contribute to tumor development. In earlier studies, WT cells in culture were found to express the low affinity nerve growth factor receptor, p75. These WT cells were capable of responding to the neurotrophin (NT) NGF, suggesting that NT may be involved in WT pathogenesis. We have examined a group of WT immunohistochemically with antibodies recognizing known trk receptor proteins, the p75 receptor, and the NTs, NGF and NT-3. Confirmatory immunoprecipitation and Western blots were then performed on representative WT samples from the study group. The p75 receptor was found predominantly in the epithelial and blastemal components where high levels of NT were also identified. The trk, A and B receptors were primarily within stromal components, whereas the trk C and C' receptors were present within epithelial structures. Western blot analyses confirmed the presence of the respective receptor proteins with variations correlating in some cases with histological type. The selective presence of NT receptors and growth factors in this series of WT implies autocrine/paracrine mechanisms for tumor development. C1 CORNELL UNIV,MED CTR,DEPT HEMATOL ONCOL,NEW YORK,NY 10021. CORNELL UNIV,MED CTR,DEPT CELL BIOL,NEW YORK,NY 10021. NCI,FREDERICK CANC RES & DEV CTR,MOLEC EMBRYOL SECT,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD. RP DONOVAN, MJ (reprint author), CHILDRENS HOSP,DEPT PATHOL,300 LONGWOOD AVE,BOSTON,MA 02115, USA. OI Tsoulfas, Pantelis/0000-0003-1974-6366 NR 38 TC 39 Z9 39 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 1994 VL 145 IS 4 BP 792 EP 801 PG 10 WC Pathology SC Pathology GA PL843 UT WOS:A1994PL84300007 PM 7943171 ER PT J AU YAMASHIRO, S TAKEYA, M NISHI, T KURATSU, J YOSHIMURA, T USHIO, Y TAKAHASHI, K AF YAMASHIRO, S TAKEYA, M NISHI, T KURATSU, J YOSHIMURA, T USHIO, Y TAKAHASHI, K TI TUMOR-DERIVED MONOCYTE CHEMOATTRACTANT PROTEIN-1 INDUCES INTRATUMORAL INFILTRATION OF MONOCYTE-DERIVED MACROPHAGE SUBPOPULATION IN TRANSPLANTED RAT-TUMORS SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ANTIGEN-INDUCED ARTHRITIS; COLONY-STIMULATING FACTOR; WHOLE KNEE-JOINT; MONOCLONAL-ANTIBODIES; IMMUNOHISTOCHEMICAL ANALYSIS; CHEMOTACTIC ACTIVITY; CRYOSTAT SECTIONS; DENDRITIC CELLS; EXPRESSION; GLIOMA AB By immunohistochemistry using anti-rat macrophage monoclonal antibodies RM-1, ED1, ED2, ED3, TRPM-3, and Ki-M2R, we studied transplanted rat tumors of 9L (rat gliosarcoma), Ad-2 (rat mammary carcinoma), and MT-P (rat malignant fibrous histiocytoma) cell lines to examine the distribution pattern of macrophages within and around the tumors. Most tumor-associated macrophages expressed RM-I, EDI, and In antigens, indicating activated macrophages. Based on differences in their immunophenotypical expression, these macrophages were distinguished into two mafor subpopulations. One expressed TRPM-3 and/or ED3, and the other was positive for ED2 and Ki-M2R The former was considered to be monocyte-derived macrophages, whereas the latter showed the immunophenotype of tissue-fixed, resident macrophages. Infiltration and distribution patterns in the two macrophage subpopulations differed in the three different tumors. Monocyte-derived, activated macrophages infiltrated into 9L- and Ad-2-transplanted tumors, which markedly produced monocyte chemoattractant protein-1 (MCP-1). Additionally, numerous ED2- and Ki-M2R-positive macrophages were observed within the Ad-2-transplanted tumors, and some of them expressed TRPM-3. However, there were few macrophages in the MT-P-transplanted tumors that showed no MCP-1 production In transplanted tumors of four MT-P/MCP-1 cell lines established by transfecting a mt MCP-I gene expression vector (pCEP4/MCP-1) into the MT-P cell line, different levels of MCP-1 production were detected which correlated well with the numbers of intratumorally infiltrated TRPM-3-positive macrophages. In contrast, ED2- and Ki-M2R-positive macrophages were not detected in any MT-P/MCP-1-transplanted tumors. MT-P/ MCP-1-transplanted tumors exhibited lower growth rate than parental MT-P-transplanted tumors. These results indicate that tumor-derived MCP-1 induces intratumoral infiltration of monocyte-derived macrophages, but not macrophages with the immunophenotype of tissue-fixed, resident type. The former poplantion of macrophages seems to have a suppuessive effect on the growth of tumors.x C1 KUMAMOTO UNIV,SCH MED,DEPT PATHOL 2,KUMAMOTO 860,JAPAN. KUMAMOTO UNIV,SCH MED,DEPT NEUROSURG,KUMAMOTO 860,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,IMMUNOPATHOL SECT,FREDERICK,MD 21701. NR 39 TC 103 Z9 106 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 1994 VL 145 IS 4 BP 856 EP 867 PG 12 WC Pathology SC Pathology GA PL843 UT WOS:A1994PL84300013 PM 7943176 ER PT J AU WARD, JM ANVER, MR HAINES, DC BENVENISTE, RE AF WARD, JM ANVER, MR HAINES, DC BENVENISTE, RE TI CHRONIC ACTIVE HEPATITIS IN MICE CAUSED BY HELICOBACTER-HEPATICUS SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CELL NUCLEAR ANTIGEN; SP-NOV; CAMPYLOBACTER-JEJUNI; GASTRIC-MUCOSA; PYLORI; INFECTION; EPITHELIUM; MOUSE; LIVER; HEPATOCARCINOGENESIS AB Helicobacter infections cause chronic gastroenteritis in humans and several animal species. We recently discovered a new Helicobacter (H. hepaticus) that is the etiological agent of a unique chronic active hepatitis in mice. Natural infection appeared to be acquired early in life in enzootically infected colonies. Liver lesions arose as focal necrosis and focal nonsuppurative inflammation by 1 to 4 months of age in susceptible mouse strains. By 6 to 8 months, extensive liver involvement included hepatocytomegaly, bile ductular (oval cell) hyperplasia, and cholangitis. Were was an age-related increase in proliferating cell nuclear antigen hepatocyte nuclear labeling index. The bacteria were usually found within bile canaliculi as determined by ultrastructural evaluation of liver lesions, the Steiner modification of the Warthin-Starry stain and immunohistochemistry with a rabbit antibody to Helicobacter pylori. Naturally infected mice showed an age related increase in serum IgG antibodies to Helicobacter hepaticus proteins. We disease was experimentally reproduced by intraperitoneal injection of litter suspensions from affected livers or bacteria cultivated in vitro We earliest lesions of the experimental disease appeared 4 weeks after injection The course of spontaneous and experimental infection was slow and insidious and resulted in high titers of antibodies to bacterial proteins. This chronic bacterial infection represents a new model of chronic liver disease C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,PATHOL HISTOTECHNOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. RP WARD, JM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,OFF LAB ANIM SCI,VET & TUMOR PATHOL SECT,FAIRVIEW 201,FREDERICK,MD 21702, USA. NR 53 TC 156 Z9 161 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 1994 VL 145 IS 4 BP 959 EP 968 PG 10 WC Pathology SC Pathology GA PL843 UT WOS:A1994PL84300024 PM 7943185 ER PT J AU VANNUCCI, SJ MAHER, F KOEHLER, E SIMPSON, IA AF VANNUCCI, SJ MAHER, F KOEHLER, E SIMPSON, IA TI ALTERED EXPRESSION OF GLUT-1 AND GLUT-3 GLUCOSE TRANSPORTERS IN NEUROHYPOPHYSIS OF WATER-DEPRIVED OR DIABETIC RATS SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE GLUCOSE UTILIZATION; STREPTOZOTOCIN-INDUCED DIABETES; DEHYDRATION ID BLOOD-BRAIN-BARRIER; INSITU HYBRIDIZATION; PLASMA VASOPRESSIN; SYSTEM AB Progressive dehydration due to water deprivation and streptozotocin diabetes both produce increased activity of the hypothalamoneurohypaphysial system and enhanced vasopressin secretion. To determine whether enhanced metabolic acitivity affects glucose transporter protein expression, this study examined the effect of these conditions on 45-kDa GLUT-1 and the neuronal glucose transporter, GLUT-3, which mediate glucose transport in the rat neurohypophysis. Progressive water deprivation increased hematocrit, plasma electrolytes Na+ and Cl-, and vasopressin over 3 days, relative to the severity of dehydration. Plasma vasopressin increased threefold by 24 h, reaching 4.5-fold by 72 h. These changes were reflected in a 56 and 75% decrease in neurohypophysial vasopressin content by 48 and 72 h, respectively. Significant changes in glucose transporters were also observed at 48 and 72 h, with GLUT-1 increasing by 18 and 44% and GLUT-3 increasing by 42 and 55%, respectively. Streptozotocin-induced diabetes produced increases in hematocrit, plasma Cl-, and vasopressin, although the magnitude of these changes was less than with dehydration. There was a twofold increase in plasma vasopressin by 3 days, commensurate with the onset of overt diabetes, and a threefold increase by 2 wk. These changes were reflected in a 30 and 40% decline in neural lobe vasopressin content, respectively. Despite the difference in the magnitude of hormone response, GLUT-3 increased by the same amount (53%) as in dehydration. GLUT-1, however, was decreased 16% by 3 days and 25% by 1 and 2 wk of diabetes. Although the opposite effects on GLUT-1 may relate to differences in circulating insulin or glucose, this study is the first demonstration of increased expression of GLUT-3 in response to a common hypothalamic signal in these two conditions. C1 PENN STATE UNIV, MILTON S HERSHEY MED CTR, DEPT PHARMACOL, HERSHEY, PA 17033 USA. NIDDKD, EXPTL DIABET METAB & NUTR SECT, DIABET BRANCH, BETHESDA, MD 20892 USA. RP VANNUCCI, SJ (reprint author), PENN STATE UNIV, MILTON S HERSHEY MED CTR, DEPT PEDIAT, HERSHEY, PA 17033 USA. FU NICHD NIH HHS [HD-25498] NR 30 TC 36 Z9 36 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD OCT PY 1994 VL 267 IS 4 BP E605 EP E611 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA PW562 UT WOS:A1994PW56200019 PM 7943311 ER PT J AU BREMER, C BRADFORD, BU HUNT, KJ KNECHT, KT CONNOR, HD MASON, RP THURMAN, RG AF BREMER, C BRADFORD, BU HUNT, KJ KNECHT, KT CONNOR, HD MASON, RP THURMAN, RG TI ROLE OF KUPFFER CELLS IN THE PATHOGENESIS OF HEPATIC REPERFUSION INJURY SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE LIVER; ELECTRON PARAMAGNETIC RESONANCE SPECTROSCOPY; FREE RADICAL ADDUCTS ID ORTHOTOPIC LIVER-TRANSPLANTATION; PERFUSED-RAT-LIVER; COLD ISCHEMIC STORAGE; PARTICLE PHAGOCYTOSIS; HYPOXIA; ACTIVATION; ENDOTOXIN; INCREASE; SURVIVAL; DEATH AB The purpose of this study was to evaluate the role of Kupffer cell activation in the pathogenesis of reperfusion injury. In a blood-free liver perfusion model, pericentral hypoxia and reperfusion injury occurred. Lactate dehydrogenase (LDH) and malondialdehyde (MDA) release, oxygen uptake, and trypan blue staining were assessed. Within the first 10 min of reflow, LDH and MDA release reached maximal values of 44 U.g(-1).h(-1) and 115 nmol.g(-1).h(-1), respectively. Trypan blue cell staining was confined to pericentral regions of the liver lobule. When Kupffer cells were inactivated with GdCl3, release of enzymes and MDA was reduced significantly by >50%, and hepatic cell death was almost completely absent. Since increases in MDA suggested involvement of free radicals, livers were perfused with phenyl N-t-butylnitrone (5 mM), a spin-trapping agent. Analysis of liver tissue by electron paramagnetic resonance spectroscopy revealed a typical six-line spectrum, providing direct evidence that carbon-centered radicals were generated on reflow. GdCl3 treatment decreased radical adduct formation by similar to 50%. Collectively, these results strongly support the hypothesis that activation of Kupffer cells plays an important role in the pathogenesis of hepatic reperfusion injury. C1 UNIV N CAROLINA, FAC LAB, DEPT PHARMACOL, HEPATOBIOL & TOXICOL LAB, CHAPEL HILL, NC 27599 USA. NIEHS, MOLEC BIOPHYS LAB, RES TRIANGLE PK, NC 27709 USA. FU NIAAA NIH HHS [AA-09156] NR 33 TC 84 Z9 85 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD OCT PY 1994 VL 267 IS 4 BP G630 EP G636 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA PW598 UT WOS:A1994PW59800018 PM 7943328 ER PT J AU VALDEZ, IH PAULAIS, M FOX, PC TURNER, RJ AF VALDEZ, IH PAULAIS, M FOX, PC TURNER, RJ TI MICROFLUOROMETRIC STUDIES OF INTRACELLULAR CA2+ AND NA+ CONCENTRATIONS IN NORMAL HUMAN LABIAL GLAND ACINI SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE SALIVARY GLANDS; FLUID SECRETION; STIMULUS-SECRETION COUPLING; FLUORESCENT DYES ID CYTOSOLIC FREE CALCIUM; MINOR SALIVARY-GLANDS; RAT PAROTID ACINI; CYCLIC ADP-RIBOSE; SJOGRENS SYNDROME; INOSITOL PHOSPHATE; TUMOR PROMOTER; SUBSTANCE-P; CELLS; CA-2+ AB The responses of human labial salivary acini to muscarinic, adrenergic, and substance P peptidergic stimulation were studied using the fluorescent indicators fura 2 for intracellular Ca2+ concentration ([Ca2+](i)) and sodium-binding benzofuran isophthalate for intracellular Naf concentration ([Na+](i)). Of the agents tested (carbachol, epinephrine, isoproterenol, and substance P) only the muscarinic agonist carbachol increased [Ca2+](i) substantially above basal levels (three to fourfold; half-maximal effect similar to 1 mu M). Experiments with the Ca2+-adenosinetriphosphatase inhibitor thapsigargin indicated the presence of both thapsigargin-sensitive and thapsigargin-insensitive intracellular Ca2+ stores, both of which were mobilized by carbachol. [Na+](i) in resting labial acini was similar to 20 mM. On stimulation with carbachol, [Na+](i) rose transiently to more than three times this value and then partially recovered. This carbachol-induced rise in [Na+](i) was largely blocked by bumetanide, a specific inhibitor of the Na+-K+-2Cl(-) cotransporter. These results are consistent with an intact muscarinic fluid secretory response in human labial acini with transepithelial Cl- secretion driven via Na+-K+-2Cl(-) cotransport and the secretion of fluid presumably following Cl- loss via an apical Ca2+-dependent anion channel, as observed in salivary acini from other species. C1 NIDR, CLIN INVEST & PATIENT CARE BRANCH, BETHESDA, MD 20892 USA. RI Paulais, Marc/E-5623-2017 NR 38 TC 11 Z9 11 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD OCT PY 1994 VL 267 IS 4 BP G601 EP G607 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA PW598 UT WOS:A1994PW59800014 PM 7943325 ER PT J AU GOLOMB, E ABASSI, ZA CUDA, G STYLIANOU, M PANCHAL, VR TRACHEWSKY, D KEISER, HR AF GOLOMB, E ABASSI, ZA CUDA, G STYLIANOU, M PANCHAL, VR TRACHEWSKY, D KEISER, HR TI ANGIOTENSIN-II MAINTAINS, BUT DOES NOT MEDIATE, ISOPROTERENOL-INDUCED CARDIAC-HYPERTROPHY IN RATS SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE C-FOS; LOSARTAN; POLYMERASE CHAIN REACTION ID LEFT-VENTRICULAR HYPERTROPHY; GENE-EXPRESSION; C-FOS; ESSENTIAL-HYPERTENSION; MYOCARDIAL GROWTH; PROTO-ONCOGENE; HEART; CAPTOPRIL; MASS AB The role of angiotensin II (ANG II) in the development of isoproterenol (Iso)-induced cardiac hypertrophy was examined in rats. Iso increased cardiac mass, left ventricular RNA-to-DNA ratio, and the cardiac content of both myosin heavy chain and hydroxyproline in a dose-dependent manner, indicating that Iso-induced cardiac hypertrophy involves growth of both muscle and connective tissue. Cardiac hypertrophy reverted within 11-14 days after cessation of Iso. Propranolol prevented development of Iso-induced cardiac hypertrophy but did not affect the rate of its reversal. The ANG IT receptor blocker losartan (Los) did not significantly decrease the hypertrophic response to Iso. Los injected after cessation of Iso dramatically enhanced the reversal of cardiac hypertrophy, even in rats that received Los with Iso during the induction of Iso-induced cardiac hypertrophy. ANG II, injected continuously at a subpressor dose that did not affect heart weight when given alone, inhibited reversal of cardiac hypertrophy when given after cessation of Iso. Los did not significantly affect the induction of the protooncogene c-fos by Iso. We conclude that endogenous ANG II has a major function in maintaining Iso-induced cardiac hypertrophy but does not mediate its induction. This suggests that different interactive stimuli may be required for development of cardiac hypertrophy, i.e., for initiation and for maintenance. C1 NHLBI, MOLEC CARDIOL BRANCH, BETHESDA, MD 20892 USA. NHLBI, BIOSTAT RES BRANCH, BETHESDA, MD 20892 USA. RP GOLOMB, E (reprint author), NHLBI, HYPERTENS ENDOCRINE BRANCH, BLDG 10, RM 8C103, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. RI Cuda, Giovanni/F-5359-2012 OI Cuda, Giovanni/0000-0001-6313-1866 NR 33 TC 27 Z9 31 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD OCT PY 1994 VL 267 IS 4 BP H1496 EP H1506 PG 11 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA PW587 UT WOS:A1994PW58700033 ER PT J AU SOLLOTT, SJ LAKATTA, EG AF SOLLOTT, SJ LAKATTA, EG TI NOVEL METHOD TO ALTER LENGTH AND LOAD IN ISOLATED MAMMALIAN CARDIAC MYOCYTES SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE CARDIAC MYOCYTES; STRETCH; AUXOTONIC CONTRACTION; LENGTH-DEPENDENT CALCIUM MYOFILAMENT ACTIVATION; LOAD-DEPENDENT RELAXATION ID PIG VENTRICULAR MYOCYTES; SINGLE HEART-CELLS; CONTRACTILE-FORCE; TENSION DEVELOPMENT; PAPILLARY-MUSCLE; SARCOMERE-LENGTH; CALCIUM; RELAXATION; INTACT; ACTIVATION AB We have devised a novel technique enabling reversible gradations in the resting and contraction length of intact mammalian ventricular myocytes of up to 15-18% over slack length. Enzymatically isolated single cells are embedded in a transparent, elastic, cross-linked fibrin matrix, contained within a narrow elastic tube. Reversible gradations in cell length are produced via fibrin matrix stretch, produced by stretching the tube. Simultaneous measurement of cell length, edge motion, and indo 1 fluorescence during auxotonic contractions permits characterization of cell contractile function. Although force cannot be directly measured, the time integral of contractile force (i.e., relative contractile impulse, a contractile index that is independent of shortening constraints) is derived combining myocyte shortening and matrix loading. Relatively small degrees of myocyte stretch produce a lightly afterloaded model dominated by variations in preload in which there is parallel augmentation of shortening and contractile impulse (force) development. At higher degrees of stretch, significant afterloading is introduced, resulting in the development of an inverse relationship between shortening and impulse (approaching isometric conditions). Length-dependent Ca2+ myofilament activation and load-dependent relaxation are readily demonstrated in intact isolated mammalian ventricular myocytes. RP SOLLOTT, SJ (reprint author), NIA, CTR GERONTOL RES, CARDIOVASC SCI LAB, 4940 EASTERN AVE, BALTIMORE, MD 21224 USA. NR 49 TC 7 Z9 8 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD OCT PY 1994 VL 267 IS 4 BP H1619 EP H1629 PG 11 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA PW587 UT WOS:A1994PW58700048 ER PT J AU MEHLMAN, PT HIGLEY, JD FAUCHER, I LILLY, AA TAUB, DM VICKERS, J SUOMI, SJ LINNOILA, M AF MEHLMAN, PT HIGLEY, JD FAUCHER, I LILLY, AA TAUB, DM VICKERS, J SUOMI, SJ LINNOILA, M TI LOW CSF 5-HIAA CONCENTRATIONS AND SEVERE AGGRESSION AND IMPAIRED IMPULSE CONTROL IN NONHUMAN-PRIMATES SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CEREBROSPINAL-FLUID MONOAMINE; DISRUPTIVE BEHAVIOR DISORDERS; DNA HYBRIDIZATION EVIDENCE; BIOGENIC-AMINE METABOLISM; 5-HYDROXYINDOLEACETIC ACID; RHESUS-MONKEYS; HOMOVANILLIC-ACID; SEROTONIN METABOLISM; VIOLENT OFFENDERS; PLASMA-CORTISOL AB Objective: The purpose of this study was to examine the relationship between behavior and serotonin by using a nonhuman primate model of aggression and impulse control. Method: During a routine capture and medical examination, 26 adolescent male rhesus macaques (Macaca mulatta) were selected as subjects from a free-ranging population of 4,500 rhesus monkeys inhabiting a 475-acre sea island. Physiological data were obtained front 22-23 of the subjects. Blood and CSF samples were obtained, and each subject was fitted with a radio transmitter collar for rapid location. The subjects were released into their social groups, and quantitative behavioral observations were made over a 3-month period. Results: CSF 5-hydroxyindoleacetic acid (5-HIAA) concentrations were inversely correlated with ''escalated'' aggression, i.e., a measure of more intense or severe aggression as defined by the ratio of chases and Physical assaults to all aggressive acts. CSF 5-HIAA concentrations were significantly lower in those subjects who showed evidence of physical wounding than in subjects with no wounds. Low CSF 5-HIAA concentrations were also correlated with greater risk-taking as determined by an analysis of leaping behaviors in the forest canopy. The ratio of long leaps (leaps that traversed the longest distances at dangerous heights) to all leaps was negatively correlated with CSF 5-HIAA concentrations. Conclusions: Adolescent male rhesus macaques with low CSF 5-HIAA concentrations are at risk for 1) exhibiting more violent forms of aggressive behavior and 2) loss of impulse control as evidenced by greater risk tracking during movement through the forest canopy. C1 US FDA,ROCKVILLE,MD 20857. NICHHD,CTR ANIM,COMPARAT ETHOL LAB,POOLESVILLE,MD. NIAAA,DIV INTRAMURAL CLIN & BIOL RES,CLIN STUDIES LAB,BETHESDA,MD 20892. RP MEHLMAN, PT (reprint author), LAB ANIM BREEDERS & SERV,DIV PRIMATE BREEDING BEHAV,POB 557,YEMASSEE,SC 29945, USA. NR 80 TC 281 Z9 283 U1 2 U2 16 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 OCT PY 1994 VL 151 IS 10 BP 1485 EP 1491 PG 7 WC Psychiatry SC Psychiatry GA PJ937 UT WOS:A1994PJ93700014 PM 7522411 ER PT J AU TOBIN, MB SCHMIDT, PJ RUBINOW, DR AF TOBIN, MB SCHMIDT, PJ RUBINOW, DR TI REPORTED ALCOHOL-USE IN WOMEN WITH PREMENSTRUAL-SYNDROME SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Note ID SOCIAL DRINKERS AB Women with prospectively confirmed premenstrual syndrome (N=21) reported greater alcohol use than comparison subjects (N=16) in a longitudinal study. The difference in reported alcohol use was not confined to the premenstruum, nor did it correlate with dysphoric symptoms or cravings for food premenstrually. RP TOBIN, MB (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BEHAV ENDOCRINOL SECT,BLDG 10,RM 3N238,BETHESDA,MD 20892, USA. NR 9 TC 27 Z9 27 U1 0 U2 0 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 OCT PY 1994 VL 151 IS 10 BP 1503 EP 1504 PG 2 WC Psychiatry SC Psychiatry GA PJ937 UT WOS:A1994PJ93700019 PM 8092343 ER PT J AU RILEY, GF POTOSKY, AL LUBITZ, JD BROWN, ML AF RILEY, GF POTOSKY, AL LUBITZ, JD BROWN, ML TI STAGE OF CANCER AT DIAGNOSIS FOR MEDICARE HMO AND FEE-FOR-SERVICE ENROLLEES SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID HEALTH MAINTENANCE ORGANIZATION; BREAST-CANCER; COLORECTAL-CANCER; INTERVIEW SURVEY; PROSTATE-CANCER; MAMMOGRAPHY; MORTALITY; BLACK; WOMEN; CARE AB Objectives. Health maintenance organizations (HMOs) with Medicare contracts often provide cancer screening and preventive services not covered under fee-for-service. This study compared cancer patients in HMOs and fee-for-service on stage at diagnosis. Methods. The study examined stage at diagnosis for aged Medicare enrollees in HMOs and fee-for-service, using information from the Surveillance, Epidemiology, and End Results program, linked with Medicare enrollment files. Twelve cancer sites were investigated, and demographics, area of residence, year of diagnosis (1985 to 1989), and education at the census tract level were controlled. Results. HMO enrollees were diagnosed at earlier stages for cancers of the female breast, cervix, colon, and melanomas and at later stages for stomach cancer. There were no differences for cancers of the prostate, rectum, buccal cavity and pharynx, bladder, uterus, kidney, and ovary. HMO effects were strongest in areas with large, mature HMOs. Conclusions. Compared with fee-for-service enrollees, HMO enrollees were diagnosed at earlier stages for cancer sites for which effective screening services are available. The earlier detection of certain cancers among HMO enrollees may result from coverage of screening services and, perhaps, promotion by HMOs of such services. C1 NCI,BETHESDA,MD 20892. RP RILEY, GF (reprint author), US HLTH CARE FINANCING ADM,RM 2504,OAK MEADOWS BLDG,6325 SECUR BLVD,BALTIMORE,MD 21207, USA. NR 33 TC 125 Z9 126 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD OCT PY 1994 VL 84 IS 10 BP 1598 EP 1604 DI 10.2105/AJPH.84.10.1598 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PM435 UT WOS:A1994PM43500009 PM 7943477 ER PT J AU GOMEZ, R ROMERO, R GALASSO, M BEHNKE, E INSUNZA, A COTTON, DB AF GOMEZ, R ROMERO, R GALASSO, M BEHNKE, E INSUNZA, A COTTON, DB TI THE VALUE OF AMNIOTIC-FLUID INTERLEUKIN-6, WHITE BLOOD-CELL COUNT, AND GRAM STAIN IN THE DIAGNOSIS OF MICROBIAL INVASION OF THE AMNIOTIC CAVITY IN PATIENTS AT TERM SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 22-26, 1994 CL CHICAGO, IL SP SOC GYNECOL INVESTIGAT DE PREMATURE RUPTURE OF MEMBRANES; TERM PARTURITION; INTRAUTERINE INFECTION; AMNIOCENTESIS; CHORIOAMNIONITIS ID PRETERM PREMATURE RUPTURE; INTRAAMNIOTIC INFECTION; GLUCOSE-CONCENTRATION; LEUKOCYTE ESTERASE; MEMBRANES; LABOR; WOMEN; PARTURITION AB PROBLEM: Subclinical microbial invasion of the amniotic cavity occurs in 18.8% of women with term labor and intact membranes and in 34% of patients with term PROM and is a risk factor for the development of puerperal infection related morbidity. Although amniotic fluid white blood cell count, interleukin-6 determination, and Gram stain examination have been used for the diagnosis of intrauterine infection in patients with preterm labor and preterm premature rupture of membranes, no information is available about the accuracy and specific cut-off values for these tests in patients at term. The purpose of this study was to compare the performance of the amniotic fluid Gram stain examination, white blood cell count, and interleukin-6 determination in the identification of microbial invasion of the amniotic cavity in patients at term with and without PROM. METHOD: Amniotic fluid was retrieved from 148 patients with term gestations (90 patients with spontaneous labor and intact membranes and 58 patients with PROM). Samples were cultured for bacteria and Mycoplasma species. Amniotic fluid Gram stain, white blood cell count, and interleukin-6 determinations (ELISA, sensitivity: 43 pg/ml) were performed Bethesda, Maryland in all samples. Microbial invasion of the amniotic cavity was defined as a positive amniotic fluid culture for microorganisms. Analysis was conducted using Mann-Whitney U test, Fisher's exact test, receiver operating characteristic curves and logistic regression. RESULTS: Patients with spontaneous labor and intact membranes: The prevalence of microbial invasion of amniotic cavity in this group was 15.6% (14/90). The most sensitive test for the detection of microbial invasion of the amniotic cavity was amniotic fluid interleukin-6 determination (sensitivity for: interleukin-6 greater than or equal to 5.7 ng/ml = 86%, white blood cell count greater than or equal to 20 cells/mm(3) = 64%, Gram stain = 28%). The most specific test was the Gram stain of the amniotic fluid (specificity for: Gram stain = 84%, interleukin-6 = 79% and white blood cell count = 63%). Multiple logistic regression demonstrated that amniotic fluid interleukin-6 concentration was the only covariate that retained statistical significance when intrauterine infection was used as outcome variable. Patients with PROM: The prevalence of a positive amniotic fluid culture in this group was 39.7% (23/58). Logistic regression demonstrated that only interleukin-6 retained a significant relationship with the results of amniotic culture when all variables were entered simultaneously into a model to predict amniotic fluid culture results. The most sensitive tests for the detection of intrauterine infection were interleukin-6 determination and white blood cell count (sensitivity for interleukin-6 greater than or equal to 3.4 ng/ml and white blood cell count greater than or equal to 20 cells/mm(3) = 69.6% for both). The most specific test was Gram stain (97.1%). CONCLUSIONS: Amniotic fluid interleukin-6 determination is the best rapid test for the detection of microbial invasion of the amniotic cavity in patients at term with and without PROM, When this test is not available, amniotic fluid Gram stain and white blood cell count represent valid diagnostic tools to assess the microbial state of amniotic cavity. C1 NICHHD,PERINATOL RES BRANCH,BETHESDA,MD. SOTERO DEL RIO HOSP,SANTIAGO,CHILE. RP GOMEZ, R (reprint author), WAYNE STATE UNIV,HUTZEL HOSP,DEPT OBSTET & GYNECOL,4707 ST ANTOINE BLVD,DETROIT,MI 48201, USA. NR 20 TC 50 Z9 51 U1 0 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 8755-8920 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD OCT PY 1994 VL 32 IS 3 BP 200 EP 210 PG 11 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA PX424 UT WOS:A1994PX42400013 PM 7533501 ER PT J AU SHAHAR, E FOLSOM, AR MELNICK, SL TOCKMAN, MS COMSTOCK, GW SHIMAKAWA, T HIGGINS, MW SORLIE, PD SZKLO, M AF SHAHAR, E FOLSOM, AR MELNICK, SL TOCKMAN, MS COMSTOCK, GW SHIMAKAWA, T HIGGINS, MW SORLIE, PD SZKLO, M TI DOES DIETARY VITAMIN-A PROTECT AGAINST AIRWAY-OBSTRUCTION SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRES; SERUM RETINOL; BETA-CAROTENE; LIMITATIONS; CANCER AB A recent report based on data from the first National Health and Nutrition Examination Survey suggested that tow intake of vitamin A may be associated with a greater risk of airway obstruction. We attempted to replicate these findings in a population-based sample of middle-aged adults (n = 15,743) who participated in the baseline examination of the Atherosclerosis Risk in Communities (ARIC) Study. Vitamin A intake was estimated from a 66-item food frequency questionnaire, and the presence of airway obstruction was determined by spirometry. Although airway obstruction was associated in ARIC with well-established risk factors such as age, sex, and smoking, there was little evidence for a role of vitamin A. With only one exception, vitamin A intake was unrelated to airway obstruction in all smoking categories using either categorical or continuous measures of lung function (FEV(1), FVC, FEV(1)/FVC). Only among current smokers in the upper tertile of lifetime cigarette smoking (> 41 pack-years) was the odds ratio of having airway obstruction for the lowest quartile of vitamin A intake compared with the highest quartile elevated (1.7 [95% confidence interval 1.1 to 2.7]). Despite some biological plausibility that vitamin A intake may prevent obstructive lung disease, the inability to demonstrate association in a larger population study, with better estimation of usual dietary intake, casts doubt on the existence of causal relationship C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD. RP SHAHAR, E (reprint author), UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,1300 S 2ND ST,SUITE 300,MINNEAPOLIS,MN 55454, USA. FU NHLBI NIH HHS [N01-HC-55018, N01-HC-55016, N01-HC-55015] NR 23 TC 32 Z9 34 U1 0 U2 4 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT PY 1994 VL 150 IS 4 BP 978 EP 982 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA PM789 UT WOS:A1994PM78900017 PM 7921473 ER PT J AU SHARP, DS RODRIGUEZ, BL SHAHAR, E HWANG, LJ BURCHFIEL, CM AF SHARP, DS RODRIGUEZ, BL SHAHAR, E HWANG, LJ BURCHFIEL, CM TI FISH CONSUMPTION MAY LIMIT THE DAMAGE OF SMOKING ON THE LUNG SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; UNSATURATED FATTY-ACIDS; DIETARY SUPPLEMENTATION; PULMONARY-FUNCTION; CIGARETTE-SMOKING; OIL; GENERATION; PSORIASIS; SMOKERS; INVITRO AB High fish consumption is characteristic of Japanese-American men of the Honolulu Heart Program (HHP). Analyses of data from the Atherosclerosis Risk in Communities (ARIC) study suggest high fish intake protects the lu ng against smoking damage. Measurements of forced expiratory volume in 1 s (FEV(1)) and smoking status in the HHP cohort were done at the first examination in 1965-68. Among 8,006 men, 45 to 68 yr, 6,346 had acceptable spirograms. Within current smokers, 1,545 men consumed fish less than twice a week, and 1,264 ate fish twice a week or more. Controlling for cigarettes/d, age, height, and daily calories, separate regression models indicated an average decrease of -10.1 ml for each additional yr of smoking (95% Confidence Interval [Cl]: -13.6, -6.5) at low levels of fish intake, and a decrease of -4.4 ml (95% Cl: -8.2, -0.6) at high levels. The coefficients were significantly different (p = 0.03). These differences reflect a predicted FEV(1) 144 ml (95% Cl: 62, 227) higher in the high fish group at greater than or equal to 40 yr of smoking, but no difference at less than or equal to 35 yr. Similar analyses were conducted for cigarettes/d. On average, the FEV(1) decline for each additional cigarette/d was not significantly different among subjects with low versus high fish intake. However, the predicted FEV(1) at less than or equal to 30 cigarettes/d was 52 ml (95% Cl: 17, 87) higher in the high fish consumption group No significant difference in FEV(1) was noted between groups at > 30 cigarettes/d. These findings suggest that the protective role of fish is ''saturated'' at higher ''doses'' of cigarette smoking. C1 NHLBI,HONOLULU HEART PROGRAM,BETHESDA,MD. UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,MINNEAPOLIS,MN. RP SHARP, DS (reprint author), KUAKINI MED CTR,HONOLULU HEART PROGRAM,347 N KUAKINI ST,HONOLULU,HI 96817, USA. FU NHLBI NIH HHS [N01-HC-02901] NR 28 TC 47 Z9 49 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT PY 1994 VL 150 IS 4 BP 983 EP 987 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA PM789 UT WOS:A1994PM78900018 PM 7921474 ER PT J AU KONG, LY LUSTER, MI DIXON, D OGRADY, J ROSENTHAL, GJ AF KONG, LY LUSTER, MI DIXON, D OGRADY, J ROSENTHAL, GJ TI INHIBITION OF LUNG IMMUNITY AFTER INTRATRACHEAL INSTILLATION OF BENZO(A)PYRENE SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID TUMOR-NECROSIS-FACTOR; MACROPHAGE CYTO-TOXICITY; NITRIC-OXIDE; PULMONARY CARCINOGENICITY; GAMMA-INTERFERON; F344 RATS; CELLS; MICE; BENZOPYRENE; EXPOSURE AB Benzo(a)pyrene (B(a)P) has been shown to suppress systemic immunity in experimental animals, which may contribute to the growth of the chemical-induced tumors. However, its effects on lung immunity after inhalation, a common route for human exposure in urban areas, has not been determined. These studies examine intratracheal B(a)P instillation on lung natural killer (NK) cell activity, alveolar macrophage (AM) functions, and susceptibility to tumor cell challenge in Fischer 344 (F-344) rats. Adult female F-344 rats were given a single intratracheal instillation of 0, 10, 20, or 40 mg B(a)P/kg body weight as a suspension, and lung NK cell activity and AM functions were examined 7, 21, or 100 d later. Although exposure to B(a)P did not alter cell recovery after lavage, histologic changes were observed as evidenced by granulomatous inflammation and squamous metaplasia. There was a slight but significant suppression of H2O2 and nitric oxide (NO) release from alveolar macrophages of treated animals as well as NK cell activity from the lung digest. A marked suppression of tumor necrosis factor alpha (TNF alpha) and interleukin (IL-1) secretion in LPS-and/or cytokine-activated alveolar macrophages occurred. The suppressive effects were generally more severe on Day 7 after exposure than on Days 21 or 100, although IL-1 remained depressed through Day 100 after exposure. B(a)P exposure allowed for the increased growth of MADB106 metastatic tumor cells in the lung. These tumor cells were shown to be highly sensitive to lysis by immune-mediators, including TNF alpha. Taken together, these results indicated that NK cell activity and particularly secretory products produced by AM are sensitive targets for instilled B(a)P, and altered lung immunity may play a role in allowing for the growth of lung tumors. C1 NIEHS,INTEGRAT BIOL LAB,ENVIRONM IMMUNOL & NEUROBIOL SECT,RES TRIANGLE PK,NC 27709. NIEHS,EXPTL PATHOL LAB,RES TRIANGLE PK,NC 27709. UNIV STRATHCLYDE,DEPT IMMUNOL,STRATHCLYDE,SCOTLAND. NR 39 TC 19 Z9 20 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT PY 1994 VL 150 IS 4 BP 1123 EP 1129 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA PM789 UT WOS:A1994PM78900039 PM 7921446 ER PT J AU CHERNIACK, RM ABRAMS, J KALICA, AR AF CHERNIACK, RM ABRAMS, J KALICA, AR TI PULMONARY-DISEASE ASSOCIATED WITH BREAST-CANCER THERAPY SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material C1 NHLBI,DIV LUNG DIS,BETHESDA,MD 20892. NATL JEWISH CTR IMMUNOL & RESP MED,DEPT MED,DENVER,CO 80206. NCI,DIV CANC TREATMENT,ROCKVILLE,MD. NR 0 TC 25 Z9 26 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT PY 1994 VL 150 IS 4 BP 1169 EP 1173 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA PM789 UT WOS:A1994PM78900047 PM 7921454 ER PT J AU BROWN, ML HOUN, F AF BROWN, ML HOUN, F TI QUALITY ASSURANCE AUDITS OF COMMUNITY SCREENING MAMMOGRAPHY PRACTICES - AVAILABILITY OF ACTIVE FOLLOW-UP FOR DATA-COLLECTION AND OUTCOME ASSESSMENT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID BREAST-CANCER AB OBJECTIVE. Routine and periodic mammography audit studies, the systematic evaluation of clinical follow-up procedures and outcomes subsequent to screening mammography reports of abnormal findings, have been advocated as an important component of quality assurance in screening mammography. This study assessed the degree to which mammography facilities in community practice maintain reporting and record-keeping systems and ascertain sufficient clinical follow-up data to facilitate the practice of mammography audit studies. MATERIALS AND METHODS. As part of a national survey of 1057 mammography facilities, data were collected from a stratified subsample of 50 facilities on facility information systems, and facility records were systematically abstracted to determine the degree of completeness of clinical follow-up data to screening mammography examinations with abnormal findings. Facilities were assisted in obtaining additional information through active data follow-up, and this information also was entered into the study's database. RESULTS. The nature of mammography information systems and the degree of data completeness varied widely. Computerized systems were used at relatively few facilities (12%). The organization of records and data varied widely and was generally not designed to accommodate routine systematic analysis. Screening examinations could be identified without reading the actual text of the mammography report at 94% of the facilities, but reports had to be read at the majority of facilities to identify examinations with abnormal findings (70%). Before active data follow-up, records were incomplete in about 40% of all cases. After active data follow-up, this decreased to 16%. Forty-two facilities achieved an average completeness of more than 90%, whereas the remaining eight lagged significantly behind this level. CONCLUSION, At the time of this study (late 1992 to early 1993), only about 20% of the facilities surveyed had informational systems and sufficient ascertainment of data to support the practice of mammography audit studies. After active data follow up, more than 80% of the facilities were willing and able to achieve a high degree of data completeness with the assistance of our data abstracters. The results of this study suggest that, with the advent of standardized mammography data collection and analysis systems and increased emphasis on clinical outcomes assessment as a standard of care, the practice of performing mammography audits, although not currently widespread, is feasible for most facilities. C1 US FDA,CTR DEVICES & RADIOL HLTH,OFF HLTH & IND PROG,DIV MAMMOG QUAL & RADIAT PROG,ROCKVILLE,MD 20857. RP BROWN, ML (reprint author), NCI,DIV CANC PREVENT & CONTROL,SURVEILLANCE PROG,APPL RES BRANCH,EXECUT PLAZA N,RM 313,BETHESDA,MD 20855, USA. NR 12 TC 11 Z9 11 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 OCT PY 1994 VL 163 IS 4 BP 825 EP 829 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PH683 UT WOS:A1994PH68300011 PM 8092017 ER PT J AU DOPPMAN, JL SHAWKER, TH FRAKER, DL ALEXANDER, HR SKARULIS, MC LACK, EE SPIEGEL, AM AF DOPPMAN, JL SHAWKER, TH FRAKER, DL ALEXANDER, HR SKARULIS, MC LACK, EE SPIEGEL, AM TI PARATHYROID ADENOMA WITHIN THE VAGUE NERVE SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Note C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. GEORGETOWN UNIV,SCH MED,DEPT PATHOL,WASHINGTON,DC 20007. NIDDKD,OFF DIRECTOR,BETHESDA,MD 20892. RP DOPPMAN, JL (reprint author), NIH,HENRY M JACKSON FDN,WARREN G MAGNUSON CLIN CTR,DEPT RADIOL,BETHESDA,MD 20892, USA. NR 8 TC 9 Z9 9 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 OCT PY 1994 VL 163 IS 4 BP 943 EP 945 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PH683 UT WOS:A1994PH68300036 PM 8092040 ER PT J AU KROGSTAD, DJ SUZUKI, M LONG, CA AOKI, Y ISHII, A JAMES, SL AF KROGSTAD, DJ SUZUKI, M LONG, CA AOKI, Y ISHII, A JAMES, SL TI DRUG DISCOVERY, DEVELOPMENT AND DEPLOYMENT - A REPORT FROM THE 28TH JOINT CONFERENCE OF THE US-JAPAN PARASITIC DISEASES PANELS, BALTIMORE, MARYLAND, JULY 1993 SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID KINETOPLAST DNA MINICIRCLES; PLASMODIUM-FALCIPARUM; ARTEMISININ QINGHAOSU; MALARIA PARASITE; HEMOGLOBIN DEGRADATION; ONCHOCERCA-VOLVULUS; IVERMECTIN; PROTEASE; CLEAVAGE; INVITRO AB The 28th Joint Conference of the Parasitic Diseases Panels of the U.S.-Japan Cooperative Medical Sciences Program held in Baltimore, Maryland focused on current research within both countries on antiparasitic chemotherapy. This meeting report summarizes presentations of work in progress on antiparasitic drugs currently in use and drugs under development or in clinical trials, as well as reports on potentially unique parasite characteristics that may provide targets for development of future therapeutics. C1 HAHNEMANN UNIV,PHILADELPHIA,PA 19102. GUNMA UNIV,SCH MED,MAEBASHI,GUMMA 371,JAPAN. NAGASAKI UNIV,NAGASAKI 852,JAPAN. NATL INST HLTH,TOKYO 162,JAPAN. NIAID,BETHESDA,MD 20892. RP KROGSTAD, DJ (reprint author), TULANE UNIV,SCH PUBL HLTH & TROP MED,NEW ORLEANS,LA 70112, USA. FU NIAID NIH HHS [R22 AI-26848, AI-29971, P01 AI-15351] NR 22 TC 0 Z9 0 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 OCT PY 1994 VL 51 IS 4 BP 384 EP 388 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA PN553 UT WOS:A1994PN55300002 PM 7943561 ER PT J AU AVSICZUPANC, T POLJAK, M FURLAN, P KAPS, R XIAO, SY LEDUC, JW AF AVSICZUPANC, T POLJAK, M FURLAN, P KAPS, R XIAO, SY LEDUC, JW TI ISOLATION OF A STRAIN OF A HANTAAN VIRUS FROM A FATAL CASE OF HEMORRHAGIC-FEVER WITH RENAL SYNDROME IN SLOVENIA SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID POLYMERASE CHAIN-REACTION; NEPHROPATHIA-EPIDEMICA VIRUS; SEQUENCE-ANALYSIS; UNITED-STATES; DOBRAVA VIRUS; CELL-CULTURE; HANTAVIRUS; RNA; YUGOSLAVIA; DISEASE AB Hemorrhagic fever with renal syndrome (HFRS) has been serologically confirmed in Slovenia during the last seven years. There is evidence that three hantaviruses (Hantaan, Puumala, and a newly described form termed Dobrava) circulate simultaneously in this area. Recently, a hantavirus was isolated from the urine and brain tissue of a fatal case of HFRS. Positive immunofluorescent reactions with reference human sera and monoclonal antibodies were first recognized after the second cell culture passage. Extensive cross-reactivity between our isolate and prototype Hantaan virus, strain 76-118, and Hantaan-like isolates from the former Yugoslavia, Fojnica and Plitvice, was revealed by enzyme-linked immunosorbent assay with specific rat antisera. The reaction pattern of the isolate was similar to the prototype Hantaan virus by indirect immunofluorescent assay with a panel of monoclonal antibodies. Furthermore, the specificity of the isolates was confirmed by analysis of polymerase chain reaction products of this virus with five restriction endonucleases. This appears to be the first isolation of a strain of prototype Hantaan virus from a fatal case of HFRS in Europe. C1 REG HOSP NOVO MESTO,NOVO MESTO,SLOVENIA. NIAID,BETHESDA,MD 20892. USA,MED RES INST INFECT DIS,FREDERICK,MD. RP AVSICZUPANC, T (reprint author), UNIV LJUBLJANA FAC MED,INST MICROBIOL,ZALOSKA 4,LJUBLJANA 61105,SLOVENIA. RI Xiao, Shu-Yuan/E-2215-2012 NR 28 TC 15 Z9 16 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 OCT PY 1994 VL 51 IS 4 BP 393 EP 400 PG 8 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA PN553 UT WOS:A1994PN55300004 PM 7943563 ER PT J AU FEIR, D SANTANELLO, CR LI, BW XIE, CS MASTERS, E MARCONI, R WEIL, G AF FEIR, D SANTANELLO, CR LI, BW XIE, CS MASTERS, E MARCONI, R WEIL, G TI EVIDENCE SUPPORTING THE PRESENCE OF BORRELIA-BURGDORFERI IN MISSOURI SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID POLYMERASE CHAIN-REACTION; LYME-DISEASE SPIROCHETE; IXODES-DAMMINI ACARI; AMBLYOMMA-AMERICANUM; DERMACENTOR-VARIABILIS; IXODIDAE; SCAPULARIS; SPIROCHAETACEAE; TRANSMISSION; OKLAHOMA AB Although Lyme disease is commonly seen in the southcentral United States, the epidemiology of the disease is poorly defined there. The purpose of this study was to document the presence of Borrelia burgdorferi in ticks collected in southeastern Missouri and around the city of St. Louis. Spirochetes were detected and identified as B. burgdorferi by immunofluorescent antibody (IFA) tests using the monoclonal antibody H5332 in 1.9% of Amblyomma americanum and 2.0% of Dermacentor variabilis ticks collected. The identity of IFA-positive organisms was verified by polymerase chain reactions (PCRs) with two different sets of B. burgdorferi-specific primers followed by Southern blotting. The DNA sequences of amplified 371-basepair PCR products from two positive Missouri ticks showed 97-98% identity with that obtained by the same method for the B31 strain of B. burgdorferi. These results confirm that B. burgdorferi is present in questing D. variabilis and A. americanum ticks in areas of Missouri where Lyme disease occurs. Additional studies are needed to determine the role of these ticks in the epidemiology of Lyme disease in Missouri and neighboring states. C1 FAMILY PHYS GRP,CAPE GIRARDEAU,MO 63701. US PHS,ROCKY MT LAB,HAMILTON,MT 59840. JEWISH HOSP ST LOUIS,DEPT INFECT DIS,DIV INFECT DIS,ST LOUIS,MO 63110. RP FEIR, D (reprint author), ST LOUIS UNIV,DEPT BIOL,ST LOUIS,MO 63101, USA. NR 19 TC 34 Z9 34 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 OCT PY 1994 VL 51 IS 4 BP 475 EP 482 PG 8 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA PN553 UT WOS:A1994PN55300016 PM 7943575 ER PT J AU BERGER, SL AF BERGER, SL TI EXPANDING THE POTENTIAL OF RESTRICTION ENDONUCLEASES - USE OF HAPAXOTERMINISTIC ENZYMES SO ANALYTICAL BIOCHEMISTRY LA English DT Article AB A new class of restriction endonucleases called hapaxoterministic enzymes, hapaxomers for short, has been defined. A hapaxomer cleaves DNA outside the recognition site or within an interrupted ''palindrome'' at bases which are not specified producing fragments with asymmetric, staggered ends. Such termini are unique; in the general case, the protrusions of a fragment obtained with the aid of a hapaxomer cannot self-hybridize, nor can the fragment be ligated to the vast majority of other fragments produced by the same enzyme. When the fragments generated by a hapaxoterministic enzyme are mixed, they can reassemble in only one configuration-that of the original structure from which they were derived. Hapaxomers, then, are characterized not by their recognition sites, which may be symmetric or asymmetric, but by their cleavage sites. The ability to reunite once-contiguous fragments efficiently means that hapaxomers cleaving DNA at many locations are virtually equivalent to restriction enzymes cutting at unique sites. These properties can be exploited for applications such as site-specific mutagenesis or the isolation of large intact DNA fragments. (C) 1994 Academic Press, Inc. RP BERGER, SL (reprint author), NCI,BIOCHEM LAB,GENES & GENE PROD SECT,BETHESDA,MD 20892, USA. NR 5 TC 11 Z9 11 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD OCT PY 1994 VL 222 IS 1 BP 1 EP 8 DI 10.1006/abio.1994.1445 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PM439 UT WOS:A1994PM43900001 PM 7856834 ER PT J AU GAO, WY JOHNS, DG MITSUYA, H AF GAO, WY JOHNS, DG MITSUYA, H TI ENZYMATIC ASSAY FOR QUANTIFICATION OF DEOXYNUCLEOSIDE TRIPHOSPHATES IN HUMAN-CELLS EXPOSED TO ANTIRETROVIRAL 2',3'-DIDEOXYNUCLEOSIDES SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID DNA-POLYMERASE; AZIDOTHYMIDINE AB Quantification of intracellular 2'-deoxynucleoside- 5'-triphosphates (dNTPs) is of importance in studies of antiretroviral 2',3'-dideoxynucleoside analogs (ddNs) and a highly sensitive enzymatic assay for dNTPs has frequently been used for this purpose. However, the susceptibility of the assay to interference from the corresponding substrate analogs, ddNTPs, is still undefined. Ideally, DNA polymerases used in the assay should meet at least two criteria: (i) high fidelity to the template even in the presence of ddNTPs and (ii) low affinity for ddNTPs. None of the currently used exonuclease-free Klenow and Sequenase enzymes met both criteria. However, Sequenase had higher fidelity to the template than did the Klenow enzyme in the presence of pyrimidine-ddNTPs, and its reaction followed first order kinetics. We have, therefore relying primarily on Sequenase, designed a dNTP proportional reduction assay to correct the ddN-induced deviation in the enzymatic assay. With the use of high-fidelity exonuelease-free DNA polymerase and the application of correction factors, we now can accurately quantify dNTPs with a minimum detection limit as low as 0.1 pmol, using as few as 1 X 10(4) peripheral blood mononuclear cells. The method described should be useful in the study and development of antiretroviral ddNs. (C) 1994 Academic Press, Inc. C1 NCI,MED CHEM LAB,BETHESDA,MD 20892. RP GAO, WY (reprint author), NCI,MED BRANCH,EXPTL RETROVIROL SECT,BLDG 10,ROOM 5A24,BETHESDA,MD 20892, USA. NR 12 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD OCT PY 1994 VL 222 IS 1 BP 116 EP 122 DI 10.1006/abio.1994.1462 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PM439 UT WOS:A1994PM43900018 PM 7856836 ER PT J AU SHENG, HZ LIN, PX NELSON, PG AF SHENG, HZ LIN, PX NELSON, PG TI ANALYSIS OF MULTIPLE HETEROGENEOUS MESSENGER-RNAS IN SINGLE CELLS SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID SERUM GROWTH-FACTORS; GENE-EXPRESSION; NERVOUS-SYSTEM; MESSENGER-RNA; C-FOS; TRANSCRIPTION FACTOR; FACTORS ENCODES; ALPHA-SUBUNIT; RAT-BRAIN; JUN AB We describe a two-stage amplification procedure designed to analyze multiple heterogeneous mRNA from single cells. Using an oligo(dT) primer with an attached phage promoter, the whole mRNA pool from a single cell was first transcriptionally amplified. This step brings the weak signal from one cell to a range in which it can be reliably picked up by the polymerase chain reaction (PCR) procedure. The cDNA was then divided for separate PCR amplification to obtain an unambiguous signal for each gene product. The linear amplification of phage transcription increased the convenience and reliability of detecting multiple messengers in the second stage, The procedure is extremely sensitive because it combines the amplification generated by both phage transcription and PCR. Using a pAW109 artificial RNA, we demonstrated that this procedure detects 10 copies of pAW109 RNA per original sample with 90% confidence and 50 copies per sample with >95% confidence. This procedure of multiple mRNA analysis allows ''phenotyping'' of any cell for its mRNA composition. Examples involving several immediate early genes and subunits of the gamma-aminobutyric acid, receptor genes are given. The method should greatly facilitate the analysis of combinatorial expression of various regulatory or channel molecules in their native environments. The procedure should also provide a direct and efficient way of decoding the developmental instruction coded through combinatorial transcriptional regulation. (C) 1994 Academic Press, Inc. RP SHENG, HZ (reprint author), NICHHD,DEV NEUROBIOL LAB,BLDG 6B,ROOM 2B-211,BETHESDA,MD 20892, USA. NR 29 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD OCT PY 1994 VL 222 IS 1 BP 123 EP 130 DI 10.1006/abio.1994.1463 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PM439 UT WOS:A1994PM43900019 PM 7856837 ER PT J AU BERGER, SL AF BERGER, SL TI RESCUE OF A FAILED POLYMERASE CHAIN-REACTION CATALYZED BY VENT OR DEEP VENT DNA-POLYMERASE WITH 10-PERCENT DIMETHYL-SULFOXIDE SO ANALYTICAL BIOCHEMISTRY LA English DT Note ID PROTHYMOSIN-ALPHA GENE; PCR AMPLIFICATION; SPECIFICITY; FIDELITY; DMSO RP BERGER, SL (reprint author), NCI,GENES & GENE PROD SECT,BETHESDA,MD 20892, USA. NR 18 TC 3 Z9 3 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD OCT PY 1994 VL 222 IS 1 BP 290 EP 293 DI 10.1006/abio.1994.1490 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PM439 UT WOS:A1994PM43900046 PM 7856867 ER PT J AU LUBARSKY, DA HAHN, C BENNETT, DH SMITH, LR BREDEHOEFT, SJ KLEIN, HG REVES, JG AF LUBARSKY, DA HAHN, C BENNETT, DH SMITH, LR BREDEHOEFT, SJ KLEIN, HG REVES, JG TI THE HOSPITAL COST (FISCAL YEAR 1991/1992) OF A SIMPLE PERIOPERATIVE ALLOGENEIC RED-BLOOD-CELL TRANSFUSION DURING ELECTIVE SURGERY AT DUKE-UNIVERSITY SO ANESTHESIA AND ANALGESIA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-C VIRUS; SCREENED BLOOD; INFECTION; RISK; HIV AB We sought to determine the actual cost to Duke University Medical Center of a perioperative red blood cell transfusion. A recent audit at Duke University Medical Center determined the base average direct and indirect hospital costs for providing a unit of red blood cells. The Transfusion Service's base cost for providing an allogeneic unit of red blood cells was $113.58. To obtain the actual hospital cost of transfusing a unit of red blood cells in the perioperative period, associated costs were calculated and added to the Transfusion Service's base cost. These associated costs included compatibility tests on multiple units per each unit transfused in the perioperative period, performing ABO and Rh typing and antibody screening on samples from patients who were not subsequently transfused, compatibility tests on units not issued, handling costs of units issued but not used, physically administering the blood, and the cost of the recipient contracting an infectious disease or developing a transfusion reaction. These associated costs increased the cost of transfusing an allogeneic unit of red blood cells in the perioperative period to $151.20. Perhaps the techniques described in the study can be used to quantify cost/benefit ratios associated with future changes in transfusion practice. C1 DUKE UNIV,MED CTR,DEPT COMMUNITY & FAMILY MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT PATHOL,DURHAM,NC 27710. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. RP LUBARSKY, DA (reprint author), DUKE UNIV,MED CTR,DEPT ANESTHESIOL,VASCULAR & THORAC ANESTHESIA SECT,BOX 3094 DUMC,DURHAM,NC 27710, USA. NR 19 TC 39 Z9 38 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD OCT PY 1994 VL 79 IS 4 BP 629 EP 637 PG 9 WC Anesthesiology SC Anesthesiology GA PJ932 UT WOS:A1994PJ93200003 PM 7943767 ER PT J AU KOLOBOW, T TSUNO, K ROSSI, N APRIGLIANO, M AF KOLOBOW, T TSUNO, K ROSSI, N APRIGLIANO, M TI DESIGN AND DEVELOPMENT OF ULTRATHIN-WALLED, NONKINKING ENDOTRACHEAL-TUBES OF A NEW NO-PRESSURE LARYNGEAL SEAL DESIGN - A PRELIMINARY-REPORT SO ANESTHESIOLOGY LA English DT Article DE EQUIPMENT, CUFFS ENDOTRACHEAL TUBES AB Background: Endotracheal tubes (ETTs) of conventional design and manufacture greatly increase the air-flow resistance of the upper airways. This increase in upper-airway resistance can lead to a significant increase in the work of breathing and may necessitate the use of assisted mechanical ventilation. Current ETTs are relatively stiff and contribute greatly to patient discomfort. The inflatable cuffs now mounted onto the ETTs function well in short-term use but impart significant morbidity when used over longer periods. These issues were addressed by the designing of a low-resistance ETT. Methods: Using new techniques, we developed ultrathin-walled, wire reinforced ETTs of conventional configuration and ETTs the oropharyngeal-section diameter of which was a few millimeters larger than the diameter of the tracheal section. The wall thickness was a constant 0.20 mm. The wire reinforcement was stainless steel flat wire or superelastic nickel-titanium alloy. The superelastic nickel-titanium alloy reinforcement made those ETTs crush-proof; after forceful manual compression, recovery was complete. To obtain a seal with the upper airways, we first shaped a short section of the oropharyngeal section of the ETT from round to oval (or egg-shaped) to conform better to the larynx. We then attached to this segment numerous soft, pliable, 0.025-0.075-mm-thick rings of polyurethane to occlude voids for potential air leaks from within the larynx. Results: In vitro pressure-flow studies showed a decrease by as much as four- or fivefold in air-flow resistance in the adult ETT range, effectively increasing the internal diameter by 2.3-3.7 mm, compared with conventional ETTs of the same outside diameter. In vivo studies for 24 h in sheep showed no air leaks at airway pressures to 30 cmH(2)O and minimal leak at greater pressures. The gross appearance of the trachea was normal. Conclusions: Although the new tubes appear to offer advantages to those currently used, testing in humans is required to assess the clinical utility of the tube-cuff design. RP KOLOBOW, T (reprint author), NHLBI,CELL BIOL LAB,9000 ROCKVILLE PIKE,BLDG 10,ROOM 5D17,BETHESDA,MD 20892, USA. NR 10 TC 13 Z9 13 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD OCT PY 1994 VL 81 IS 4 BP 1061 EP 1067 DI 10.1097/00000542-199410000-00031 PG 7 WC Anesthesiology SC Anesthesiology GA PK614 UT WOS:A1994PK61400032 PM 7943817 ER PT J AU EISENSTEIN, EM SNELLER, MC AF EISENSTEIN, EM SNELLER, MC TI COMMON VARIABLE IMMUNODEFICIENCY - DIAGNOSIS AND MANAGEMENT SO ANNALS OF ALLERGY LA English DT Review ID X-LINKED AGAMMAGLOBULINEMIA; T-CELL; HYPOGAMMAGLOBULINEMIC PATIENTS; VARIED IMMUNODEFICIENCY; VIRUS-INFECTION; GAMMA-GLOBULIN; IMMUNOGLOBULIN; INTERLEUKIN-2; DEFICIENCY; LYMPHOCYTES AB Objective. Common variable immunodeficiency is a heterogeneous syndrome characterized by humoral immunodeficiency, recurrent bacterial infections, and a variety of immunologic abnormalities. The goal of this article is to review the pathogenesis, clinical manifestations, diagnosis, and management of common variable immunodeficiency. Data Sources. References are limited to the English language literature. Sources include computerized databases and bibliographies of recent articles and books. Study Selection. References that made important contributions to our understanding of the pathogenesis, clinical manifestations, diagnosis, and treatment of this disease were selected for inclusion in this review. Results and Conclusion. Common variable immunodeficiency is an idiopathic state of immune dysregulation that results in impaired antibody synthesis and the development of recurrent bacterial infections. This syndrome is also associated with a variety of autoimmune and neoplastic disorders. Effective management of these patients includes intravenous immuno-globulin replacement, vigorous treatment of infections, and readiness to promptly evaluate and treat unusual autoimmune and neoplastic complications should they appear. C1 NIAID,IMMUNOREGULAT LAB,IMMUNOL DIS SECT,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BETHESDA,MD 20892. NR 62 TC 34 Z9 35 U1 0 U2 0 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 SN 0003-4738 J9 ANN ALLERGY JI Ann. Allergy PD OCT PY 1994 VL 73 IS 4 BP 285 EP 292 PG 8 WC Allergy SC Allergy GA PN194 UT WOS:A1994PN19400003 PM 7943995 ER PT J AU LICHT, T PASTAN, I GOTTESMAN, M HERRMANN, F AF LICHT, T PASTAN, I GOTTESMAN, M HERRMANN, F TI P-GLYCOPROTEIN-MEDIATED MULTIDRUG-RESISTANCE IN NORMAL AND NEOPLASTIC HEMATOPOIETIC-CELLS SO ANNALS OF HEMATOLOGY LA English DT Review DE CHEMORESISTANCE; CHEMOSENSITIZING AGENTS; GENE THERAPY; MULTIDRUG RESISTANCE; P-GLYCOPROTEIN ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MDR1 GENE-EXPRESSION; MULTIPLE-DRUG RESISTANCE; ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; BONE-MARROW CELLS; BACTERIAL TRANSPORT PROTEINS; ACUTE MYELOBLASTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMA; MONOCLONAL-ANTIBODIES AB The multidrug transporter, P-glycoprotein (P-gp), is expressed by CD34-positive bone marrow cells, which include hematopoietic stem cells, and in other cells in the bone marrow and peripheral blood, including some lymphoid cells. Multidrug resistance mediated by P-gp appears to be a major impediment to successful treatment of acute myeloid leukemias and multiple myelomas. However, the impact of P-gp expression on prognosis has to be confirmed in several other hematopoietic neoplasms. The role of P-gp in normal and malignant hematopoiesis and clinical attempts to circumvent multidrug resistance in hematopoietic malignancies are reviewed. The recent transduction of the MDR1 gene into murine hematopoietic cells, which protects them from toxic effects of chemotherapy, suggests that MDR1 gene therapy may help prevent myelosuppression following chemotherapy. C1 FREE UNIV BERLIN,KLINIKUM RUDOLF VIRCHOW,ROBERT ROSSLE CANC CTR,DEPT MED ONCOL & APPL MOLEC BIOL,D-13122 BERLIN,GERMANY. MAX DELBRUCK CTR MOLEC MED,D-13122 BERLIN,GERMANY. NCI,DCBC,CELL BIOL LAB,BETHESDA,MD 20892. NCI,DCBC,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 173 TC 49 Z9 50 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0939-5555 J9 ANN HEMATOL JI Ann. Hematol. PD OCT PY 1994 VL 69 IS 4 BP 159 EP 171 DI 10.1007/BF02215949 PG 13 WC Hematology SC Hematology GA PL609 UT WOS:A1994PL60900001 PM 7948302 ER PT J AU TROENDLE, JF YU, KF AF TROENDLE, JF YU, KF TI A NOTE ON TESTING THE HARDY-WEINBERG LAW ACROSS STRATA SO ANNALS OF HUMAN GENETICS LA English DT Note AB The problem of testing the Hardy-Weinberg law when the data are stratified in K strata is considered. Previous methods lose power when the departure from the law is irregular from stratum to stratum. Two methods based on the squared distance are proposed to overcome this problem. Simulations show that the new methods can have a dramatic improvement over the previous methods. The methods are applied to red cell glyoxalase genotype data from populations in India. RP TROENDLE, JF (reprint author), NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,BLDG 6100,ROOM 7B13,BETHESDA,MD 20892, USA. NR 8 TC 14 Z9 14 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD OCT PY 1994 VL 58 BP 397 EP 402 DI 10.1111/j.1469-1809.1994.tb00735.x PN 4 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA PT708 UT WOS:A1994PT70800008 PM 7864594 ER PT J AU SKARULIS, M BONDY, C AF SKARULIS, M BONDY, C TI RISKS AND BENEFITS OF INSULIN-LIKE GROWTH-FACTOR - REPLY SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 NICHHD,BETHESDA,MD 20892. RP SKARULIS, M (reprint author), NIDDK,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 1 PY 1994 VL 121 IS 7 BP 550 EP 550 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PJ102 UT WOS:A1994PJ10200023 ER PT J AU RICHFIELD, EK HERKENHAM, M AF RICHFIELD, EK HERKENHAM, M TI SELECTIVE VULNERABILITY IN HUNTINGTONS-DISEASE - PREFERENTIAL LOSS OF CANNABINOID RECEPTORS IN LATERAL GLOBUS-PALLIDUS SO ANNALS OF NEUROLOGY LA English DT Article ID STRIATAL PROJECTION NEURONS; BASAL GANGLIA; RAT-BRAIN; LOCALIZATION; CHOREA AB Selective neuronal vulnerability is a key feature of the neuropathology of Huntington's disease. We used [H-3]CP-55,940, a synthetic cannabinoid, to label cannabinoid receptors in tissue sections from individuals dying with Huntington's disease and from normal control subjects. The density of cannabinoid receptors in striatum and pallidum was measured using quantitative autoradiography. There was a greater loss of cannabinoid receptors on striatal nerve terminals in the lateral pallidum compared to the medial pallidum, in Huntington's disease of all neuropathological grades. The disparity in binding density between the lateral and medial pallidum increased with higher grades of disease. There was also a greater loss of receptors in the lateral pallidum than in the putamen. The disproportionate loss of receptors in the lateral pallidum compared to the putamen increased in magnitude with severity of neuropathological grade. These data support the relative preferential loss or dysfunction of striatal neurons projecting to the lateral pallidum compared to neurons projecting to the medial pallidum. Terminals in the lateral pallidum containing cannabinoid receptors may be affected earlier or more severely than terminals in the medial pallidum, and both pallidal segments may be affected before or more severely than cell bodies or dendrites in the striatum. Terminal loss of markers may represent a response to perikaryal injury or dysfunction, or less likely, may indicate the primary site of neuronal damage in Huntington's disease. C1 UNIV ROCHESTER,SCH MED & DENT,DEPT NEUROL,ROCHESTER,NY 14642. UNIV ROCHESTER,SCH MED & DENT,DEPT PHARMACOL,ROCHESTER,NY 14642. NIMH,FUNCT NEUROANAT SECT,BETHESDA,MD 20892. OI Herkenham, Miles/0000-0003-2228-4238 FU NIA NIH HHS [AGO 9016-01]; NIMH NIH HHS [MH 40381] NR 40 TC 107 Z9 109 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 OCT PY 1994 VL 36 IS 4 BP 577 EP 584 DI 10.1002/ana.410360406 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA PM607 UT WOS:A1994PM60700005 PM 7944290 ER PT J AU KRUSE, B BARKER, PB VANZIJL, PCM DUYN, JH MOONEN, CTW MOSER, HW AF KRUSE, B BARKER, PB VANZIJL, PCM DUYN, JH MOONEN, CTW MOSER, HW TI MULTISLICE PROTON MAGNETIC-RESONANCE SPECTROSCOPIC IMAGING IN X-LINKED ADRENOLEUKODYSTROPHY SO ANNALS OF NEUROLOGY LA English DT Article ID CHAIN FATTY-ACIDS; HUMAN BRAIN INVIVO; CHILDHOOD ADRENOLEUKODYSTROPHY; MR SPECTROSCOPY; ADRENOMYELONEUROPATHY; CELLS; ABNORMALITY; INVOLVEMENT; SPECTRA; DISEASE AB Multislice proton magnetic resonance spectroscopic imaging permits metabolic analysis of brain tissue in vivo by data acquisition in four oblique axial slices, each 15-mm thick and divided into 0.8-ml single-volume elements. We applied this technique to the systematic study of 25 patients with adrenoleukodystrophy: 3 with the severe childhood or adult cerebral form of the disease, 5 with adrenomyeloneuropathy, 12 with no demonstrable neurological involvement, and 5 women heterozygous for adrenoleukodystrophy who had some degree of neurological disability. Abnormalities on magnetic resonance spectroscopic imaging included a reduction in N-acetyl aspartate, an increase in choline-containing compounds, and at times, an increase in lactate. Five patients showed abnormalities in the presence of normal-appearing magnetic resonance images, and in 8 other patients the alterations on spectroscopic images were more severe than those demonstrable by magnetic resonance imaging. Correlation with clinical course suggests that an increase in the choline-containing compounds is associated with an active demyelinative process, whereas such compounds are not elevated in lesions that are stable. We conclude that magnetic resonance spectroscopic imaging is a more sensitive indicator of early neurological involvement than is magnetic resonance imaging, and that the character of abnormalities detected by the former technique may serve as a gauge of the degree of activity of the demyelinating process and as a guide to the selection,and evaluation of therapeutic approaches. C1 KENNEDY KRIEGER INST,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT RADIOL,BALTIMORE,MD 21205. NIH,DIAGNOST RADIOL RES LAB,BETHESDA,MD 20892. RI van Zijl, Peter/B-8680-2008; Duyn, Jozef/F-2483-2010; Moonen, Chrit/K-4434-2016 OI Moonen, Chrit/0000-0001-5593-3121 FU NCRR NIH HHS [RR 00035, RR 00052]; NICHD NIH HHS [HD 10981] NR 43 TC 103 Z9 103 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 OCT PY 1994 VL 36 IS 4 BP 595 EP 608 DI 10.1002/ana.410360408 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA PM607 UT WOS:A1994PM60700007 PM 7944292 ER PT J AU LEONMONZON, M ILLA, I DALAKAS, MC AF LEONMONZON, M ILLA, I DALAKAS, MC TI POLYMYOSITIS IN PATIENTS INFECTED WITH HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I - THE ROLE OF THE VIRUS IN THE CAUSE OF THE DISEASE SO ANNALS OF NEUROLOGY LA English DT Article ID TROPICAL SPASTIC PARAPARESIS; INCLUSION-BODY MYOSITIS; MEDIATED CYTO-TOXICITY; INFLAMMATORY MYOPATHIES; MUSCLE; ANTIBODIES; MYELOPATHY; PATHOGENESIS; RETROVIRUS; ACTIVATION AB To investigate the mechanism of polymyositis in human T-cell leukemia virus type I (HTLV-I) infection, we studied 6 HTLV-I-positive patients, 3 with polymyositis and 3 with adult T-cell leukemia but without clinical signs of muscle disease, by (a) quantitative single or double immunocytochemistry on serial 4-mu m-thick muscle biopsy sections using antibodies to lymphocyte subsets, major histocompatibility complex (MHC) antigens, and HTLV-I proteins; (b) polymerase chain reaction using HTLV-I primers in the RNA and DNA extracted from 50 mu g of muscle tissue or from serial 5-mu m-thick fresh-frozen tissue sections; and (c) cocultures of the patients' HTLV-I-positive peripheral blood lymphocytes with their homologous muscles searching for replication of HTLV-I within the myotubes. In the muscle of patients with HTLV-I-associated myopathy, the predominant endomysial cells surrounding healthy muscle fibers were CD8(+) cells followed by CD4+ cells and macrophages. MHC-I antigens were ubiquitous in the muscles of all 6 patients, even in those without endomysial inflammation. HTLV-I sequences were amplified from the whole muscle biopsy specimens but the cells harboring viral antigens were rare endomysial macrophages and not muscle fibers. Although HTLV-I sequences were amplified from all the patients' peripheral blood lymphocytes, these cells did not exert myotoxicity or resulted in viral replication in cocultures with their homologous myotubes. We conclude that in HTLV-I polymyositis (a) the HTLV-I sequences amplified from the whole muscle biopsy specimens are related to scattered HTLV-I-positive endomysial macrophages; (b) HTLV-I and HTLV-I-positive lymphocytes do not infect the muscle in vivo or in vitro; and (c) the virus, which persists in tissues other than muscle, triggers the activation of autoaggressive T cells that cause a T-cell-mediated and MHC-I-restricted myocytotoxicity. C1 NINCDS,MED NEUROL BRANCH,NEUROMUSCULAR DIS SECT,BETHESDA,MD 20892. NR 35 TC 58 Z9 58 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 OCT PY 1994 VL 36 IS 4 BP 643 EP 649 DI 10.1002/ana.410360414 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA PM607 UT WOS:A1994PM60700013 PM 7944297 ER PT J AU GALE, RP WALDMANN, TA ARMITAGE, JO CAVALLI, F AF GALE, RP WALDMANN, TA ARMITAGE, JO CAVALLI, F TI RECENT PROGRESS IN B-CELL AND T-CELL LYMPHOMAS SO ANNALS OF ONCOLOGY LA English DT Note DE B-CELLS; T-CELL; LYMPHOMA; LEUKEMIA; BIOLOGY; TREATMENT C1 OSPED SAN GIOVANNI BELLINZONA,BELLINZONA,SWITZERLAND. NCI,BETHESDA,MD 20892. UNIV NEBRASKA,OMAHA,NE 68182. RP GALE, RP (reprint author), SALICK HLTH CANC INC,8201 BEVERLY BLVD,LOS ANGELES,CA 90048, USA. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 5 IS 8 BP 689 EP 696 PG 8 WC Oncology SC Oncology GA PM786 UT WOS:A1994PM78600007 PM 7826900 ER PT J AU OSHAUGHNESSY, JA DENICOFF, AM VENZON, DJ DANFORTH, D PIERCE, LJ FRAME, JN BASTIAN, A GHOSH, B GOLDSPIEL, B MILLER, L DORR, FA KEEGAN, P BENBARUCH, N MROSE, H NOONE, M COWAN, KH AF OSHAUGHNESSY, JA DENICOFF, AM VENZON, DJ DANFORTH, D PIERCE, LJ FRAME, JN BASTIAN, A GHOSH, B GOLDSPIEL, B MILLER, L DORR, FA KEEGAN, P BENBARUCH, N MROSE, H NOONE, M COWAN, KH TI A DOSE INTENSITY STUDY OF FLAC (5-FLUOROURACIL, LEUCOVORIN, DOXORUBICIN, CYCLOPHOSPHAMIDE) CHEMOTHERAPY AND ESCHERICHIA-COLI-DERIVED GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (GM-CSF) IN ADVANCED BREAST-CANCER PATIENTS SO ANNALS OF ONCOLOGY LA English DT Article DE GM-CSF; BREAST CANCER; DOSE INTENSITY ID TUMOR-NECROSIS-FACTOR; PHASE I-II; ADJUVANT CHEMOTHERAPY; ENDOTHELIAL-CELLS; STAGE-II; MACROPHAGE; CARCINOMA; INVIVO; THERAPY; MYELOSUPPRESSION AB Background: It has been demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) can ameliorate chemotherapy-induced neutropenia. The extent to which GM-CSF can increase the actual delivered dose intensity of combination chemotherapy over multiple cycles of therapy to patients with advanced breast cancer has not been well defined. We conducted a phase I/II study of dose-intensive FLAC chemotherapy (5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide) in combination with GM-CSF in patients with locally advanced and metastatic breast cancer to study the acute and cumulative toxicities, anti-tumor activity and dose-intensity achievable with this regimen. Methods: Eighty-one patients with newly diagnosed stages IIB, III and IV breast cancer who were previously untreated with chemotherapy and who had measurable disease received multiple cycles of FLAC chemotherapy plus E. coli-derived GM-CSF administered every three weeks. Results: FLAC plus GM-CSF as associated with significant cumulative hematologic toxicity. Ninety-eight percent of patients developed grade 4 neutropenia; 29% of all cycles administered required hospitalization for fever and neutropenia; 41% and 22% of cycles required red blood cell and platelet transfusions, respectively. Other significant toxicities with E. coli-derived GM-CSF included mild to moderate first dose effects (hypotension, dyspnea, abdominal cramping) in 30% of patients; late occurring anaphylactoid reactions in 11% of patients; and vascular thromboses. The average delivered dose intensities over all cycles were cyclophosphamide, 210 mg/m2/week; doxorubicin, 14.8 mg/m2/week and 5-fluorouracil, 342 mg/m2/week. The overall clinical response rates were 100% and 83% for LABC and metastatic patients, respectively. There were 23% (6/26) pathologic CR's in the LABC patients given neoadjuvant FLAC and 22% (12/54) clinical CR's in the stage IV patients. The median survival of the LABC patients has not been reached (> 26 months) and is 30 months for the stage IV patients. Conclusions: The administration of multiple cycles of FLAC plus E. coli-derived GM-CSF therapy is associated with cumulative, dose-limiting myelosuppression, especially thrombocytopenia, as well as significant clinical toxicity. A modest increase in FLAC dose intensity over the starting doses was achievable with the addition of GM-CSF. FLAC chemotherapy has substantial antitumor activity in the treatment of advanced breast cancer. The potential usefulness of FLAC plus GM-CSF must be balanced by its considerable cost and alteration in patients' quality of life due to toxicity. Combination hematopoietic growth factor strategies may be able to reduce the toxicity of FLAC and to allow further increase dose intensity. C1 NCI, BIOSTAT SECT, BETHESDA, MD 20892 USA. NCI, RADIAT ONCOL BRANCH, BETHESDA, MD 20892 USA. NATL NAVAL MED CTR, BETHESDA, MD 20814 USA. NIH, CTR CLIN, BETHESDA, MD 20892 USA. NCI, CANC THERAPY EVALUAT PROGRAM, BETHESDA, MD 20892 USA. US FDA, ROCKVILLE, MD 20857 USA. RP OSHAUGHNESSY, JA (reprint author), NCI, MED BRANCH, BETHESDA, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 54 TC 24 Z9 24 U1 0 U2 1 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 OCT PY 1994 VL 5 IS 8 BP 709 EP 716 PG 8 WC Oncology SC Oncology GA PM786 UT WOS:A1994PM78600011 PM 7826903 ER PT J AU KALVAKOLANU, DV MANNINO, SB THORNTON, A OZATO, K BORDEN, EC AF KALVAKOLANU, DV MANNINO, SB THORNTON, A OZATO, K BORDEN, EC TI TRANSCRIPTIONAL INDUCTION OF GENES BY IFN-BETA IN MOUSE CELLS IS REGULATED BY A TRANSCRIPTION FACTOR SIMILAR TO HUMAN ISGF-3 SO ANTIVIRAL RESEARCH LA English DT Article DE IFN-BETA; MURINE L929 CELL; GENE INDUCTION; TYROSINE PHOSPHORYLATION ID SYNTHETASE ME-12 GENE; PROTEIN-TYROSINE KINASE; DNA-BINDING PROTEINS; INTERFERON-ALPHA; SIGNAL-TRANSDUCTION; MOLECULAR-CLONING; GAMMA; ACTIVATION; ELEMENT; 91-KDA AB Previous studies of IFN-stimulated transcription factors in murine cells have identified a variety of trans-acting factors that bind to the IFN-stimulated response element (ISRE) whose role in gene expression remain unclear. The present investigation was undertaken to delineate the signal transduction pathway as well as to identify the transcription factors regulated by murine IFN-beta in L929 cells. Tyrosine kinase inhibitor, Genistein, abrogated gene induction and activation of transcription factors by IFN-beta. As early as 5 min after IFN-beta treatment, a transcription factor was activated in the cytoplasm which subsequently migrated into the nucleus. Anti-phosphotyrosine antibodies detected a specific transcription factor induced by mIFN-beta. Antibodies raised against human ISGF-3 subunit proteins p48, p84, p91 and p113 recognized this factor in the cytoplasm as well as in the nucleus of IFN-beta-treated L929 cells. An antibody raised against an oligopeptide of human p113 (residues 435-450) recognized the ISGF-3 complexes both in human and murine cells. However, a different antibody against the C-terminus of human p113 (residues 671-806) did not recognize the ISGF-3 like complex in mouse cells, indicating differences in the primary sequence of these proteins. C1 MED COLL WISCONSIN,CTR CANC,MILWAUKEE,WI 53226. MED COLL WISCONSIN,DEPT MICROBIOL,MILWAUKEE,WI 53226. NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892. MED COLL WISCONSIN,DEPT PEDIAT,MILWAUKEE,WI 53226. MED COLL WISCONSIN,DEPT MED,MILWAUKEE,WI 53226. NR 38 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD OCT PY 1994 VL 25 IS 2 BP 91 EP 103 DI 10.1016/0166-3542(94)90099-X PG 13 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA PK666 UT WOS:A1994PK66600002 PM 7847880 ER PT J AU TAKAHASHI, N BREITMAN, TR AF TAKAHASHI, N BREITMAN, TR TI INDUCTION OF DIFFERENTIATION AND COVALENT BINDING TO PROTEINS BY THE SYNTHETIC RETINOIDS CH55 AND AM80 SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID ACID RECEPTOR-ALPHA; ACUTE PROMYELOCYTIC LEUKEMIA; CELL-LINE HL-60; MESSENGER-RNA; HUMAN-PLASMA; GRANULOCYTIC DIFFERENTIATION; 13-CIS-4-OXORETINOIC ACID; BIOLOGICAL-ACTIVITY; ESCHERICHIA-COLI; RAR-ALPHA AB all-trans-Retinoic acid (RA) is a potent inducer in vitro of the differentiation of the human acute myeloid leukemia cell line HL60. A mechanism for RA-induced differentiation of HL60 cells may involve retinoylation (RA acylation) which is a post-translational modification of proteins occurring in many eukaryotic cell lines. Here, we found that differentiation by the synthetic retinoid (E)4-[3-(3,5-di-tert-butylphenyl)-3-oxo-1-propenyl]-benzoic acid (Ch55) was dose-dependent in serum-free medium. The synthetic retinoid 4(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenylcarbamoyl) benzoic acid (Am80) did not induce differentiation. Ch55 bound covalently to proteins of HL60 cells. In contrast, covalent binding of Am80 to HL60 proteins was much lower. Two-dimensional gel electrophoresis patterns of proteins labeled covalently by RA and Ch55 were different with few proteins labeled by both retinoids. The level of retinoylation was increased by Am80 and combinations of RA with either Ch55 or Am80 synergistically induced differentiation of HL60 cells. These results suggest that covalent modification of proteins by a retinoid may play a role in inducing differentiation of HL60 cells. In addition, the synergy seen with combinations of RA and either Ch55 or Am80 suggests that some synthetic retinoids may be active because they displace RA from intracellular sites or because they inhibit RA catabolism. (C) 1994 Academic Press, Inc. RP TAKAHASHI, N (reprint author), NCI,DIV CANC TREATMENT,BIOL CHEM LAB,DEV THERAPEUT PROGRAM,BLDG 37,ROOM 5D-02,BETHESDA,MD 20892, USA. NR 62 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD OCT PY 1994 VL 314 IS 1 BP 82 EP 89 DI 10.1006/abbi.1994.1414 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PM604 UT WOS:A1994PM60400010 PM 7944409 ER PT J AU RACCHI, M BERGAMASCHI, S GOVONI, S WETSEL, WC BIANCHETTI, A BINETTI, G BATTAINI, F TRABUCCHI, M AF RACCHI, M BERGAMASCHI, S GOVONI, S WETSEL, WC BIANCHETTI, A BINETTI, G BATTAINI, F TRABUCCHI, M TI CHARACTERIZATION AND DISTRIBUTION OF PROTEIN-KINASE-C ISOFORMS IN HUMAN SKIN FIBROBLASTS SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE PROTEIN KINASE C ISOFORMS; SIGNAL TRANSDUCTION; HUMAN SKIN FIBROBLASTS; SUBCELLULAR FRACTIONATION; PHORBOL ESTERS ID ALZHEIMERS-DISEASE FIBROBLASTS; RAT-BRAIN; EXPRESSION; HETEROGENEITY; ISOENZYMES; ISOZYMES; CALCIUM; LIGAND AB In the present study we have examined the distribution of several isoforms of protein kinase C, a lipid-regulated serine/threonine kinase essential for signal transduction and cell regulation, in cultured human skin fibroblasts. By Western blot analysis we have detected the presence of at least three of the known protein kinase C isoforms. The calcium-dependent protein kinase C alpha was primarily associated with the cytosolic fraction. Three non-calcium-dependent isoforms, protein kinases C epsilon, C delta, and C zeta, were also detected. Protein kinases C zeta and C delta were present primarily in the cytosol, while protein kinase CE was associated primarily with the membrane fraction. Binding and activity studies were consistent with the pattern of expression and distribution defined by Western blot analysis. These results provide a useful frame of reference for the study of isoform-specific effects of protein kinase C in the regulation of cell growth and metabolism. (C) 1994 Academic Press, Inc. C1 NATL INST ENVIRONM HLTH SCI,RES TRIANGLE PK,NC. SACRED HEART HOSP,ALZHEIMERS DEPT,BRESCIA,ITALY. UNIV ROMA TOR VERGATA,DEPT EXPTL MED & BIOCHEM SCI,I-00173 ROME,ITALY. RP RACCHI, M (reprint author), UNIV MILAN,IST SCI FARMACOL,VIA BALZARETTI 9,I-20133 MILAN,ITALY. RI Battaini , Fiorenzo/H-2617-2012; Govoni, Stefano/K-2965-2015; Binetti, Giuliano/K-4519-2016; OI Govoni, Stefano/0000-0002-7243-6837; Binetti, Giuliano/0000-0003-2759-5844; Racchi, Marco/0000-0002-7185-7808 NR 19 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 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD OCT PY 1994 VL 314 IS 1 BP 107 EP 111 DI 10.1006/abbi.1994.1417 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PM604 UT WOS:A1994PM60400013 PM 7944381 ER PT J AU LEIBENLUFT, E FIERO, PL RUBINOW, DR AF LEIBENLUFT, E FIERO, PL RUBINOW, DR TI EFFECTS OF THE MENSTRUAL-CYCLE ON DEPENDENT-VARIABLES IN MOOD DISORDER RESEARCH SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Review ID PLASMA BETA-ENDORPHIN; THYROTROPIN-RELEASING-HORMONE; PREOVULATORY FOLLICULAR-FLUID; NOCTURNAL MELATONIN SECRETION; FEMALE SEX-HORMONES; RAT PROLACTIN GENE; GROWTH-HORMONE; PREMENSTRUAL-SYNDROME; LUTEINIZING-HORMONE; OVULATORY CYCLE AB The purpose of this article is to review the literature on the effects of the menstrual cycle on dependent variables in mood disorder research to inform investigators which physiological measures are likely to be significantly affected by menstrual cycle fluctuations and precisely how they might be affected. The following variables are discussed: prolactin; growth hormone; the hypothalamic-pituitary-thyroid axis (including thyrotropin, triiodothyronine, and thyroxine); the hypothalamic-pituitary-adrenal axis (cortisol; corticotropin, and beta-endorphin); melatonin; sleep; body temperature; and neurotransmitter activity (serotonergic and adrenergic systems). Body temperature and plasma and urinary norepinephrine vary predictably over the menstrual cycle. Prolactin and beta-endorphin may have peaks in the periovulatory phase, whereas serotonin levels in platelet-poor plasma may reach a nadir at that time. Triiodothyronine, thyroxine, cortisol, and melatonin do not appear to vary systematically over the course of the menstrual cycle, whereas the data for growth hormone, thyrotropin, corticotropin, and sleep are inconclusive. RP LEIBENLUFT, E (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,BEHAV ENDOCRINOL SECT,BLDG 10,ROOM 4S-239,10 CTR DR MSC 1390,BETHESDA,MD 20892, USA. NR 195 TC 88 Z9 89 U1 3 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 OCT PY 1994 VL 51 IS 10 BP 761 EP 781 PG 21 WC Psychiatry SC Psychiatry GA PL044 UT WOS:A1994PL04400001 PM 7944869 ER PT J AU ALTEMUS, M SWEDO, SE LEONARD, HL RICHTER, D RUBINOW, DR POTTER, WZ RAPOPORT, JL AF ALTEMUS, M SWEDO, SE LEONARD, HL RICHTER, D RUBINOW, DR POTTER, WZ RAPOPORT, JL TI CHANGES IN CEREBROSPINAL-FLUID NEUROCHEMISTRY DURING TREATMENT OF OBSESSIVE-COMPULSIVE DISORDER WITH CLOMIPRAMINE SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; MONOAMINE METABOLITES; 5-HYDROXYINDOLEACETIC ACID; FLUOXETINE TREATMENT; DEPRESSED-PATIENTS; MAJOR DEPRESSION; ELECTROCONVULSIVE-THERAPY; TYROSINE-HYDROXYLASE; SECRETION INVITRO AB Background: This study examined the effect of longterm (mean, 19 months) treatment with clomipramine hydrochloride on cerebrospinal fluid (CSF) levels of several neuropeptides and monoamine metabolites in children and adolescents with obsessive-compulsive disorder. Methods: The CSF levels of corticotropin-releasing hormone, vasopressin, somatostatin, and oxytocin and of the monoamine metabolites 5-hydroxyindolacetic acid, homovanillic acid, and 3-methoxy-4-hydroxyphenylglycol were measured in 17 children and adolescents with obsessive-compulsive disorder before and after longterm treatment with clomipramine. Results: Treatment resulted in significant decreases in CSF levels of corticotropin-releasing hormone (mean+/-SD, 175+/-32 vs 152+/-25 pmol/L, P<.03) and vasopressin (mean+/-SD, 1.30+/-0.57 vs 0.86+/-0.54 pmol/L, P<.02) and a trend toward a decrease in somatostatin levels (mean+/-SD, 21.3+/-8.5 vs 15.3+/-9.8 pmol/L, P<.06). Treatment also significantly increased CSF oxytocin levels (mean+/-SD, 6.05+/-1.60 vs 6.70+/-1.44 pmol/L, P<.01). Significant changes in CSF monoamine metabolite levels with treatment included significant decreases in CSF levels of 5-hydroxyindolacetic acid (mean+/-SD, 109+/-31 vs 77+/-23 pmol/mL, P<.001), CSF homovanillic acid (mean+/-SD, 273+/-111 vs 237+/-101 pmol/mL, P<.04), and 3-methoxy-4-hydroxyphenylglycol (mean+/-SD, 42.4+/-10.2 vs 36.1+/-4.8 pmol/L, P<.02) and a significant increase in the homovanillic acid-5-hydroxyindolacetic acid ratio (mean+/-SD, 2.44+/-0.46 vs 3.42+/-0.84, P<.0001). Conclusions: These neuropeptide results coupled with evidence that central administration of corticotropin-releasing hormone, vasopressin, and somatostatin to laboratory animals increases arousal and acquisition of conditioned behaviors whereas central administration of oxytocin has opposite behavioral effects are consistent with a role for these neuropeptides in the pathophysiologic processes and pharmacologic treatment of obsessive-compulsive disorder. C1 NIMH,CLIN SCI LAB,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NIMH,DIV INTRAMURAL RES PROGRAMS,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. RP ALTEMUS, M (reprint author), NIMH,CLIN SCI LAB,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 3D-41,10 CTR DR,MSC 1256,BETHESDA,MD 20892, USA. NR 66 TC 68 Z9 68 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD OCT PY 1994 VL 51 IS 10 BP 794 EP 803 PG 10 WC Psychiatry SC Psychiatry GA PL044 UT WOS:A1994PL04400003 PM 7524463 ER PT J AU BUCHANAN, RW STRAUSS, ME KIRKPATRICK, B HOLSTEIN, C BREIER, A CARPENTER, WT AF BUCHANAN, RW STRAUSS, ME KIRKPATRICK, B HOLSTEIN, C BREIER, A CARPENTER, WT TI NEUROPSYCHOLOGICAL IMPAIRMENTS IN DEFICIT VS NONDEFICIT FORMS OF SCHIZOPHRENIA SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID POSTERIOR PARIETAL CORTEX; FRONTAL-LOBE; NEGATIVE SYMPTOMS; AUDITORY HALLUCINATIONS; TWINS DISCORDANT; TEST-PERFORMANCE; RHESUS-MONKEY; BASAL GANGLIA; MEMORY; HYPOFRONTALITY AB Background: Previous studies have suggested that functional impairments of the frontal and parietal lobes are related to the deficit symptoms of schizophrenia. The purpose of the current study was to examine whether neuropsychological measures of frontal and parietal lobe function differentiated deficit from nondeficit patients. Neuropsychological measures of temporal lobe function were used as contrast measures. Methods: The performance of 18 deficit and 21 nondeficit schizophrenic patients was examined on neuropsychological measures of executive, visuospatial, and memory functions, selected on the basis of their association with lesions of either the frontal, parietal, or temporal lobes. The results from the schizophrenic subgroups were compared with the results on the same measures obtained from 30 normal controls. Results: Deficit patients performed more poorly than nondeficit patients on two frontal lobe measures, the Stroop Color-Word Interference and Trails Making B tests, and one parietal lobe measure, the Mooney Faces Closure Test. There were no differences in performance on the temporal lobe measures between the two groups. Both groups performed more poorly on the tests than the normal controls. Conclusion: The results suggest that deficit patients may have greater performance impairments on neuropsychological measures associated with frontal and parietal neuropsychological abnormalities. C1 CASE WESTERN RESERVE UNIV,DEPT PSYCHOL,CLEVELAND,OH 44106. NIMH,EXPTL THERAPEUT BRANCH,ROCKVILLE,MD 20857. RP BUCHANAN, RW (reprint author), UNIV MARYLAND,SCH MED,MARYLAND PSYCHIAT RES CTR,DEPT PSYCHIAT,POB 21247,BALTIMORE,MD 21228, USA. FU NIMH NIH HHS [MH40279, MH45074, MH48225] NR 69 TC 201 Z9 204 U1 5 U2 9 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 OCT PY 1994 VL 51 IS 10 BP 804 EP 811 PG 8 WC Psychiatry SC Psychiatry GA PL044 UT WOS:A1994PL04400004 PM 7944870 ER PT J AU CHEW, E REMALEY, NA TAMBOLI, A ZHAO, JL PODGOR, MJ KLEBANOFF, M AF CHEW, E REMALEY, NA TAMBOLI, A ZHAO, JL PODGOR, MJ KLEBANOFF, M TI RISK-FACTORS FOR ESOTROPIA AND EXOTROPIA SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID STRABISMUS; AMBLYOPIA AB Objective: To identify risk factors associated with the two major types of strabismus-esotropia and exotropia-in a cohort of children followed up from gestation to age 7 years. Design: Pregnant women were enrolled in the Collaborative Project of the National Institute of Neurological Disorders and Stroke, Bethesda, Md, from 1959 to 1965 at 12 university centers. This large multidisciplinary study was designed to evaluate the developmental consequences of complications during pregnancy and the perinatal period. Data on maternal, socioeconomic, perinatal, and neonatal characteristics were collected from 39 227 children and their mothers by medical examination and interview. Examinations of the children were performed at birth, 4 months, 8 months, 1 year, and 7 years. Outcome Measures: The evaluation of the presence of strabismus was performed during follow-up examinations and confirmed at the 7-year follow-up visit. Potential risk factors for strabismus were evaluated from the maternal, socioeconomic, perinatal, and neonatal characteristics. Results: Esotropia developed in 1187 children (3.0%), and exotropia developed in 490 children (1.2%). Esotropia was more common in whites (3.9% in whites vs 2.2% in blacks, P<.0001). The occurrence of exotropia was similar in the two races (1.2% in whites and 1.3% in blacks). Results of multivariable logistic regression models showed that the risk of strabismus increased with low birth weight (P<.0001). For infants weighing 1500 g at birth compared with those weighing 4000 g at birth, the odds ratios were 3.26 (95% confidence interval, 2.50 to 4.25) for esotropia and 4.01 (95% confidence interval, 2.77 to 5.80) for exotropia. Maternal cigarette smoking during pregnancy also increased the risk of each type of strabismus (P<.0001). For offspring of mothers who smoked more than two packs of cigarettes per day compared with those whose mothers did not smoke, the odds ratios were 1.83 (95% confidence interval, 1.51 to 2.22) for esotropia and 2.32 (95% confidence interval, 1.72 to 3.13) for exotropia. Maternal age was also a significant risk factor for esotropia (P=.0005). The risk of esotropia increased with increasing age until age 34 years. In particular, the odds ratio for mothers aged 30 to 34 years relative to that for mothers aged 20 to 24 years was 1.43 (95% confidence interval, 1.19 to 1.70). Conclusions: Esotropia was more common in whites than in blacks. The occurrence of exotropia was similar in the two races. Maternal cigarette smoking during pregnancy and low birth weight were independent and important risk factors for both esotropia and exotropia. There was an increased risk of esotropia with increasing maternal age. C1 NICHHD,BETHESDA,MD 20892. RP CHEW, E (reprint author), NEI,DIV BIOMETRY & EPIDEMIOL,BLDG 31,ROOM 6A52,BETHESDA,MD 20892, USA. FU Intramural NIH HHS [Z99 EY999999] NR 24 TC 95 Z9 100 U1 0 U2 3 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 OCT PY 1994 VL 112 IS 10 BP 1349 EP 1355 PG 7 WC Ophthalmology SC Ophthalmology GA PL495 UT WOS:A1994PL49500025 PM 7945039 ER PT J AU BURKA, LT SANCHEZ, IM AHMED, AE GHANAYEM, BI AF BURKA, LT SANCHEZ, IM AHMED, AE GHANAYEM, BI TI COMPARATIVE METABOLISM AND DISPOSITION OF ACRYLONITRILE AND METHACRYLONITRILE IN RATS SO ARCHIVES OF TOXICOLOGY LA English DT Article DE METABOLISM; DISPOSITION; RATS; ACRYLONITRILE; METHACRYLONITRILE ID 2-CYANOETHYLENE OXIDE; INVITRO; TOXICITY; CYANIDE; INVIVO; MICE; IDENTIFICATION; GLUTATHIONE; MECHANISM; EXCRETION AB Aliphatic nitriles are a class of chemicals used in high volumes in the production of plastics and elastomers, in organic synthesis, and in production of a number of food packaging containers. Toxicity and metabolism of acrylonitrile (AN) are well characterized. On the other hand, minimal information is available on the toxicity or fate of structurally related, methacrylonitrile (MAN). In an attempt to predict the toxicity of MAN, the present studies were designed to compare the disposition of both nitriles in rats. After gavage administration of equimolar doses (0.87 mmol/kg) of 2-C-14-MAN or 2-C-14-AN to male F344 rats, both chemicals were well absorbed from the GI tract and distributed to all major tissues. However, major differences in the disposition of the two nitriles were observed. While approximately 39% of the administered MAN dose was eliminated as CO2 in 24 h after dosing, only 11% of an equimolar dose of AN was eliminated as such. In addition, 31% of the MAN dose was exhaled as organic volatiles in 24 h compared to less than 2% of an equivalent AN dose. MAN and acetone were identified by HPLC analysis of expired organic volatiles from MAN-treated rats. HPLC analysis showed that AN is the only organic volatile exhaled by AN-treated rats. Urinary excretion of MAN was 22% compared to 67% of an equivalent dose of AN. The major urinary metabolite from AN results from direct conjugation with GSH, whereas the major urinary metabolite from MAN results from conjugation of the epoxide with GSH. Pretreatment with phenobarbital (PB) or SKF 525A (SKF) resulted in quantitative changes in the disposition of bath nitriles. The most striking effect of these pretreatments was the increase in AN-derived radioactivity in tissues following SKF pretreatment. PB pretreatment resulted in decreased amounts of unchanged MAN elimination in expired air. In summary, the results of current work indicate that there are major quantitative differences in the metabolism and disposition of MAN and AN; however, it remains to be established if these differences reflect a different spectrum of toxicity. C1 NIEHS,BIOCHEM RISK ANAL LAB,RES TRIANGLE PK,NC 27709. UNIV TEXAS,MED BRANCH,GALVESTON,TX 77550. RP BURKA, LT (reprint author), NIEHS,EXPTL TOXICOL BRANCH,RES TRIANGLE PK,NC 27709, USA. NR 27 TC 18 Z9 18 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-5761 J9 ARCH TOXICOL JI Arch. Toxicol. PD OCT PY 1994 VL 68 IS 10 BP 611 EP 618 DI 10.1007/BF03208340 PG 8 WC Toxicology SC Toxicology GA PM787 UT WOS:A1994PM78700002 PM 7857200 ER PT J AU DUVERGER, N RADER, D BREWER, HB AF DUVERGER, N RADER, D BREWER, HB TI DISTRIBUTION OF SUBCLASSES OF HDL CONTAINING APOA-I WITHOUT APOA-II (LPA-I) IN NORMOLIPIDEMIC MEN AND WOMEN SO ARTERIOSCLEROSIS AND THROMBOSIS LA English DT Article DE IMMUNOAFFINITY CHROMATOGRAPHY; GEL FILTRATION CHROMATOGRAPHY; APOLIPOPROTEIN A-I; CHOLESTERYL ESTER TRANSFER PROTEIN; LECITHIN-CHOLESTEROL ACYLTRANSFERASE ID HIGH-DENSITY-LIPOPROTEIN; APOLIPOPROTEIN-A-I; LECITHIN-CHOLESTEROL ACYLTRANSFERASE; IMMUNOSORBENT-ASSAY ELISA; HEPATIC LIPASE; HUMAN-PLASMA; MONOCLONAL-ANTIBODY; POSTHEPARIN PLASMA; TRANSGENIC MICE; HEART-DISEASE AB Women have significantly higher plasma concentrations of high-density lipoprotein (HDL) and apolipoprotein (ape) A-I than men. Human HDL consists of two major species of apoA-I-containing lipoproteins: LpA-I (lipoprotein containing apoA-I but not apoA-II) and LpA-I:A-II (lipoprotein containing both apoA-I and apoA-II). LpA-I is itself heterogeneous and contains several subclasses of different size and composition. We analyzed LpA-I subclasses in 12 male and 12 female healthy normolipidemic adults. LpA-I concentrations were significantly higher in women (72.4 +/- 5.6 mg/dL) than in men (50.2 +/- 2.2 mg/dL) (P < .05). LpA-I was preparatively isolated from fasting plasma by immunoaffinity chromatography. Gel filtration chromatography was then used to isolate LpA-I subclasses based on size. Three major subclasses were eluted: large, medium, and small LpA-I. No differences between men and women in the size or composition of individual LpA-I subclasses were observed. In contrast, the distribution and plasma concentration of LpA-I subclasses were significantly different between men and women. As a fraction of total LpA-I, the large LpA-I was significantly higher (68.0% to 48.4%) and the medium LpA-I was significantly lower (26.4% to 44.9%) in women than in men. The fraction of small LpA-I was not significantly different. Plasma concentrations of large LpA-I in women (49.2 mg/dL) were twice that in men (24.3 mg/dL), whereas plasma concentrations of medium LpA-I (19.1 mg/dL versus 22.5 mg/dL) and small LpA-I (4.0 mg/dL versus 3.0 mg/dL) were similar in women and men. The activities and distribution of lecithin: cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) were similar between women and men. The majority of plasma LCAT and CETP were associated with large LpA-I. In conclusion, the higher HDL cholesterol and apoA-I levels in normolipidemic women compared with men are primarily associated with elevation in a specific subclass, the large LpA-I particles. This suggests that large LpA-I may be a more specific marker for risk of premature coronary heart disease. C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. NR 45 TC 24 Z9 24 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1049-8834 J9 ARTERIOSCLER THROMB JI Arterioscler. Thromb. PD OCT PY 1994 VL 14 IS 10 BP 1594 EP 1599 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PL394 UT WOS:A1994PL39400011 PM 7918309 ER PT J AU JACOBSSON, LTH KNOWLER, WC PILLEMER, S HANSON, RL PETTITT, DJ MCCANCE, DR BENNETT, PH AF JACOBSSON, LTH KNOWLER, WC PILLEMER, S HANSON, RL PETTITT, DJ MCCANCE, DR BENNETT, PH TI A CROSS-SECTIONAL AND LONGITUDINAL COMPARISON OF THE ROME CRITERIA FOR ACTIVE RHEUMATOID-ARTHRITIS (EQUIVALENT TO THE AMERICAN-COLLEGE-OF-RHEUMATOLOGY 1958 CRITERIA) AND THE AMERICAN-COLLEGE-OF-RHEUMATOLOGY 1987 CRITERIA FOR RHEUMATOID-ARTHRITIS SO ARTHRITIS AND RHEUMATISM LA English DT Article ID REVISED CRITERIA; CLASSIFICATION AB Objective. To compare the diagnostic properties of the Rome 1961 criteria for active rheumatoid arthritis (RA) and the American College of Rheumatology (ACR; formerly, the American Rheumatism Association) 1987 criteria for RA with regard to their ability to classify, diagnose, and predict outcome in RA. Methods. Analysis of cross-sectional and longitudinal data from repeated health examinations and review of clinical records of 3,509 Pima Indians followed up from January 1966 to December 1990. Results. The ACR 1987 criteria identified similar to 50% of the cases identified by the Rome 1961 criteria, in both cross-sectional and longitudinal analyses. The ACR 1987 criteria were better predictors of subsequent development of a clinically supported diagnosis and treatment with slow-acting antirheumatic drugs (both P < 0.001), but were less sensitive than the Rome 1961 criteria for detecting cases for which there already was a clinically supported diagnosis (P < 0.001). Conclusion. In a population-based analysis, the ACR 1987 criteria are less sensitive for detecting clinical disease, but predict a clinically more severe prognosis, compared with the Rome 1961 criteria. The sensitivity of both sets of criteria to identify clinical disease is improved if multiple examinations or inactive disease are taken into account. C1 NIAMSD,PHOENIX,AZ. NIDDKD,PHOENIX,AZ. NIAMSD,BETHESDA,MD. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 14 TC 27 Z9 27 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD OCT PY 1994 VL 37 IS 10 BP 1479 EP 1486 DI 10.1002/art.1780371011 PG 8 WC Rheumatology SC Rheumatology GA PM444 UT WOS:A1994PM44400010 PM 7945473 ER PT J AU RIDER, LG MILLER, FW TARGOFF, IN SHERRY, DD SAMAYOA, E LINDAHL, M WENER, MH PACHMAN, LM PLOTZ, PH AF RIDER, LG MILLER, FW TARGOFF, IN SHERRY, DD SAMAYOA, E LINDAHL, M WENER, MH PACHMAN, LM PLOTZ, PH TI A BROADENED SPECTRUM OF JUVENILE MYOSITIS - MYOSITIS-SPECIFIC AUTOANTIBODIES IN CHILDREN SO ARTHRITIS AND RHEUMATISM LA English DT Article ID IDIOPATHIC INFLAMMATORY MYOPATHY; SIGNAL RECOGNITION PARTICLE; TRANSFER RNA-SYNTHETASE; FOCAL MYOSITIS; PM-SCL; CHILDHOOD; POLYMYOSITIS; ONSET; DERMATOMYOSITIS; ANTIBODY AB Objective. Myositis-specific autoantibodies (MSA) define relatively homogenous clinical and immunogenetic patient groups in adults with idiopathic inflammatory myopathies (IIM). This study explores the usefulness of MSA in defining groups of children with myositis. Methods. Sera from 77 children with myositis and other connective tissue diseases were tested for MSA by immunoprecipitation and immunodiffusion. Clinical data were collected and analyzed. Results. The MSA anti-PL-12 (alanyl-transfer RNA synthetase), anti-Jo-1 (histidyl-tRNA synthetase), anti-signal recognition particle, and anti-Mi-2 were each identified in the sera of 12 children with IIM. In these patients, the clinical manifestations, disease courses, and responses to therapy closely resembled those in adults with the same autoantibodies. Conclusion. These observations suggest that the clinical syndromes defined by particular MSA are similar in children and adults with IIM. By defining similar clinical syndromes in children who have MSA, this study provides a basis for future studies of MSA in the idiopathic inflammatory myopathies of childhood, which may be useful in predicting the clinical courses of a subset of these patients and improving their therapy. C1 UNIV OKLAHOMA,HLTH SCI CTR,OKLAHOMA CITY,OK. UNIV WASHINGTON,SEATTLE,WA. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. CHILDRENS MEM HOSP,CHICAGO,IL. NIAMSD,BETHESDA,MD. RP RIDER, LG (reprint author), US FDA,CTR BIOL EVALUAT & RES,BLDG 29,ROOM 507,HFM-521,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 FU NIAID NIH HHS [AI-27181] NR 28 TC 49 Z9 49 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 OCT PY 1994 VL 37 IS 10 BP 1534 EP 1538 DI 10.1002/art.1780371019 PG 5 WC Rheumatology SC Rheumatology GA PM444 UT WOS:A1994PM44400018 PM 7945480 ER PT J AU WOOD, GM DAWISHA, S GOURLEY, M AF WOOD, GM DAWISHA, S GOURLEY, M TI CHARACTERISTICS OF HPRT-MUTANT T-CELL LINES IN A LUPUS PATIENT TREATED WITH CYCLOPHOSPHAMIDE SO ARTHRITIS AND RHEUMATISM LA English DT Note ID HUMAN PERIPHERAL-BLOOD; LYMPHOCYTES-T; 6-THIOGUANINE-RESISTANT LYMPHOCYTES; GENE-EXPRESSION; RECEPTOR; ERYTHEMATOSUS; FREQUENCY; CLONING; CHAIN AB This report describes T cell lines derived from a patient with subacute cutaneous lupus after treatment with intravenous pulse cyclophosphamide. We selected for mitotically active, hypoxanthine-guanine phosphoribosyltransferase-deficient (HPRT-)T cells, by culture in a selective medium containing 6-thioguanine. When HPRT- cell lines were derived 6 days after pulse cyclophosphamide (CYC) treatment, they were predominantly CD8+ and T cell receptor (TCR) gamma/delta+, producing interferon-gamma (IFN gamma). Cell lines derived 21 days after CYC treatment were CD4+, TCR alpha/beta+ and produced both IFN gamma and interleukin-4. These results support a possible role for gamma/delta+ T cells in subacute cutaneous lupus and suggest a mechanism for the therapeutic effect of CYC. C1 NIAMSD,BETHESDA,MD. US FDA,ROCKVILLE,MD. NR 19 TC 2 Z9 2 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 OCT PY 1994 VL 37 IS 10 BP 1548 EP 1552 DI 10.1002/art.1780371021 PG 5 WC Rheumatology SC Rheumatology GA PM444 UT WOS:A1994PM44400020 PM 7945481 ER PT J AU POHL, LR MARTIN, JL HARGUS, SJ AF POHL, LR MARTIN, JL HARGUS, SJ TI IMMUNOCHEMICAL METHODS OF STUDYING THE MECHANISM OF DICLOFENAC-INDUCED HEPATITIS (VOL 37, PG 1112, 1994) SO ARTHRITIS AND RHEUMATISM LA English DT Correction, Addition ID NONCOVALENT INTERACTIONS; HEPATOTOXICITY; COVALENT RP POHL, LR (reprint author), NHLBI,BETHESDA,MD, USA. NR 17 TC 0 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 OCT PY 1994 VL 37 IS 10 BP 1557 EP 1557 DI 10.1002/art.1780371024 PG 1 WC Rheumatology SC Rheumatology GA PM444 UT WOS:A1994PM44400023 PM 7945484 ER PT J AU ROBINSON, JK CRAWLEY, JN AF ROBINSON, JK CRAWLEY, JN TI ANALYSIS OF ANATOMICAL SITES AT WHICH GALANIN IMPAIRS DELAYED-NONMATCHING-TO-SAMPLE IN RATS SO BEHAVIORAL NEUROSCIENCE LA English DT Article ID CENTRAL NERVOUS-SYSTEM; MEDIAL PREFRONTAL CORTEX; VENTRAL HIPPOCAMPUS; PHOSPHOINOSITIDE TURNOVER; NUCLEUS BASALIS; WORKING MEMORY; SPATIAL MEMORY; LESIONS; NEURONS; PERFORMANCE AB Galanin, a neuropeptide that coexists with acetylcholine in the septohippocampal pathway of the rat, impairs operant delayed nonmatching to sample (DNMTS) when administered intracerebroventricularly. Microinjection experiments were conducted to determine the anatomical site or sites at which galanin acts to disrupt DNMTS. Galanin (0.1, 0.4, or 1.6 nmol) was microinjected into the ventral hippocampus, amygdala, nucleus basalis magnocellularis, prefrontal cortex, or entorhinal cortex. Galanin disrupted DNMTS in a dose-dependent manner when microinjected into the ventral hippocampus but not at the other sites tested. These findings are consistent with the ability of galanin to inhibit physiological and biochemical actions of acetylcholine in the ventral hippocampus. C1 NIMH,EXPTL THERAPEUT BRANCH,BEHAV NEUROPHARMACOL SECT,BETHESDA,MD 20892. NR 65 TC 44 Z9 45 U1 1 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD OCT PY 1994 VL 108 IS 5 BP 941 EP 950 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA PM048 UT WOS:A1994PM04800010 PM 7530011 ER PT J AU DENT, P CHOW, YH WU, J MORRISON, DK JOVE, R STURGILL, TW AF DENT, P CHOW, YH WU, J MORRISON, DK JOVE, R STURGILL, TW TI EXPRESSION, PURIFICATION AND CHARACTERIZATION OF RECOMBINANT MITOGEN-ACTIVATED PROTEIN-KINASE KINASES SO BIOCHEMICAL JOURNAL LA English DT Article ID MAP KINASE; SIGNAL-TRANSDUCTION; RAF-1 KINASE; PHOSPHORYLATION; IDENTIFICATION; P42(MAPK); PROLIFERATION; TRANSLOCATION; P44(MAPK); P21(RAS) AB Mitogen-activated protein (MAP) kinase kinases (MKKs) are dual-specificity protein kinases which activate p42(mapk) and p44(mapk) by phosphorylation of regulatory tyrosine and threonine residues. cDNAs for two isotypes of MKK, MKK1 and MKK2, have been isolated from several species. Here we describe construction of recombinant baculoviruses for high-level expression of histidine-tagged rat MKK1 and MKK2, and procedures for production of nearly homogeneous MKK1 and MKK2 fusion proteins, in both inactive and active forms. Coinfection of Sf9 cells with either MKK1 or MKK2 virus together with recombinant viruses for Raf-1, pp60(src) (Y527F) and c-Ha-Ras resulted in activations of 250-fold and 150-fold for MKK1 and MKK2 respectively. Specific activities towards kinase-defective p42(mapk) were of the order of several hundred nanomoles of phosphate transferred/min per mg of MKK protein. The Michaelis constants for both enzymes were approx. 1 mu M. Preparations of activated MKK were apparently free of Raf-1 as assessed by Western blotting. Raf-1 phosphorylated MKK1 on one major tryptic phosphopeptide, the phosphorylation of which increased with time. This phosphopeptide contained only phosphoserine and possessed neutral overall charge at pH 1.9 on two-dimensional peptide mapping. Phosphorylation of MKK1 by Raf-1 correlated with activation and reached a plateau of similar to 2 mol/mol. C1 UNIV VIRGINIA,HLTH SCI CTR,HOWARD HUGHES MED INST,DEPT MED & PHARMACOL,CHARLOTTESVILLE,VA 22908. UNIV MICHIGAN,SCH MED,DEPT MICROBIOL & IMMUNOL,ANN ARBOR,MI 48109. NCI,FREDERICK CANC RES & DEV CTR,MOLEC MECHANISMS CARCINOGENESIS LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [CA55652]; NIDDK NIH HHS [DK41077] NR 30 TC 29 Z9 30 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 OCT 1 PY 1994 VL 303 BP 105 EP 112 PN 1 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PL764 UT WOS:A1994PL76400016 PM 7945229 ER PT J AU PERRY, WL COPELAND, NG JENKINS, NA AF PERRY, WL COPELAND, NG JENKINS, NA TI THE MOLECULAR-BASIS FOR DOMINANT YELLOW AGOUTI COAT COLOR MUTATIONS SO BIOESSAYS LA English DT Article ID GENE; FAMILY; LOCUS; MICE AB Agouti expression during the middle portion of the mouse hair growth cycle induces melanocytes to synthesize yellow instead of black pigment, generating black hairs with a yellow band. Dominant agouti alleles increase the amount of yellow pigment in the coat and are associated with pleiotropic effects including obesity, diabetes and increased tumor susceptibility. Four dominant agouti alleles (A(iapy), A(iy), A(sy) and A(vy)) were recently shown to result from insertions that cause ubiquitous expression of chimeric transcripts encoding a wild-type agouti protein((1,2)). Three insertions were identified as intracisternal A-particles, which helps explain the variable coat colors and parental imprinting effects associated with some dominant agouti alleles. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 38 TC 32 Z9 32 U1 1 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0265-9247 J9 BIOESSAYS JI Bioessays PD OCT PY 1994 VL 16 IS 10 BP 705 EP 707 DI 10.1002/bies.950161002 PG 3 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA PP094 UT WOS:A1994PP09400001 PM 7980472 ER PT J AU HOLMAN, GD CUSHMAN, SW AF HOLMAN, GD CUSHMAN, SW TI SUBCELLULAR-LOCALIZATION AND TRAFFICKING OF THE GLUT4 GLUCOSE-TRANSPORTER ISOFORM IN INSULIN-RESPONSIVE CELLS SO BIOESSAYS LA English DT Review ID RAT ADIPOSE-CELLS; PLASMA-MEMBRANE; 3T3-L1 CELLS; INTRACELLULAR SEQUESTRATION; PHOSPHORYLATION STATE; RECEPTOR SUBSTRATE-1; BINDING PROTEINS; SKELETAL-MUSCLE; PHORBOL ESTER; NH2 TERMINUS AB The rate-limiting step in the uptake and metabolism of D-glucose by insulin target cells is thought to be glucose transport mediated by glucose transporters (primarily the GLUT4 isoform) localized to the plasma membrane. However, subcellular fractionation, photolabelling and immunocytochemical studies have shown that the pool of GLUT4 present in the plasma membrane is only one of many subcellular pools of this protein. GLUT4 has been found in occluded vesicles at the plasma membrane, clathrin-coated pits and vesicles, early endosomes, and tubulo-vesicular structures; the latter are analogous to known specialized secretory compartments. Tracking the movement of GLUT4 through these compartments, and defining the mechanism and site of action of insulin in stimulating this subcellular trafficking, are major topics of current investigation. Recent evidence focuses attention on the exocytosis of GLUT4 as the major site of insulin action. Increased exocytosis may be due to decreased retention of glucose transporters in an intracellular pool, or possibly to increased assembly of a vesicle docking and fusion complex. Although details are unknown, the presence in GLUT4 vesicles of a synapto-brevin homologue leads us to propose that a process analogous to that occurring in synaptic vesicle trafficking is involved in the assembly of GLUT4 vesicles into a form suitable for fusion with the plasma membrane. Evidence that the pathways of signalling from the insulin receptor and of GLUT4 vesicle exocytosis may converge at the level of the key signalling enzyme, phosphatidylinositol 3-kinase, is discussed. C1 NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. RP HOLMAN, GD (reprint author), UNIV BATH,DEPT BIOCHEM,CLAVERTON DOWN,BATH BA2 7AY,AVON,ENGLAND. NR 59 TC 119 Z9 120 U1 0 U2 7 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0265-9247 J9 BIOESSAYS JI Bioessays PD OCT PY 1994 VL 16 IS 10 BP 753 EP 759 DI 10.1002/bies.950161010 PG 7 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA PP094 UT WOS:A1994PP09400009 PM 7980479 ER PT J AU CHIN, GJ PAYZA, K PRICE, DA GREENBERG, MJ DOBLE, KE AF CHIN, GJ PAYZA, K PRICE, DA GREENBERG, MJ DOBLE, KE TI CHARACTERIZATION AND SOLUBILIZATION OF THE FMRFAMIDE RECEPTOR OF SQUID SO BIOLOGICAL BULLETIN LA English DT Article ID NEUROPEPTIDE-FF RECEPTORS; SOMATOSTATIN RECEPTORS; PHE-MET-ARG-PHE-NH2 FMRFAMIDE; GUANINE-NUCLEOTIDES; MORPHINE-TOLERANCE; SPINAL-CORD; RAT-BRAIN; PEPTIDES; BINDING; GENE AB The optic lobe of squid (Loligo pealei) contains FMRFamide receptors that can bind an iodinated FMRFamide analog: [I-125]-desaminoTyr-Phe-norLeu-Arg-Phe-amide ([I-125]-daYFnLRFa). Radioligand binding assays revealed that squid FMRFamide receptors are specific, saturable, high affinity sites (K-d = 0.15 nM) densely concentrated in optic lobe membranes (B-max = 237 fmole/mg protein). The receptors appeared to be coupled to G(s) because guanine nucleotides inhibit receptor binding and the stimulation of adenylate cyclase by FMRFamide is GTP-dependent. Both the binding and cyclase data showed that FMRFamide, but not FMRF-OH, interacts at FMRFamide receptors; thus the C-terminal Arg-Phe-amide is critical for binding. The high binding affinity of FMRFamide (0.4 nM IC50) was specific for FMRFamide-like peptides. The structure-activity relations of many FMRFamide analogs were defined in detail and were nearly identical for both the membrane-bound and detergent-solubilized receptors. We also found that squid optic lobe contains FMRFamide-like reactivity as measured with both a radioimmunoassay and a radioreceptor assay. Moreover, we have sequenced a fragment of genomic DNA that encodes a FMRFamide precursor. Our findings in sum suggest that FMRFamide is a neurotransmitter in squid optic lobe, and that this tissue is a good source from which to purify FMRFamide receptors. C1 NICHHD,CELLULAR & MOLEC NEUROPHYSIOL LAB,BETHESDA,MD 20892. UNIV FLORIDA,WHITNEY LAB,ST AUGUSTINE,FL 32086. FU NHLBI NIH HHS [HL28440] NR 43 TC 29 Z9 33 U1 0 U2 1 PU MARINE BIOLOGICAL LABORATORY PI WOODS HOLE PA BIOLOGICAL BULL MBL STREET, WOODS HOLE, MA 02543 SN 0006-3185 J9 BIOL BULL JI Biol. Bull. PD OCT PY 1994 VL 187 IS 2 BP 185 EP 199 DI 10.2307/1542241 PG 15 WC Biology; Marine & Freshwater Biology SC Life Sciences & Biomedicine - Other Topics; Marine & Freshwater Biology GA PR255 UT WOS:A1994PR25500008 PM 7811788 ER PT J AU OZAKI, N ROSENTHAL, NE MAZZOLA, P CHIUEH, CC HARDIN, T GARCIABORREGUERO, D SCHWARTZ, PJ TURNER, E OREN, DA MURPHY, DL AF OZAKI, N ROSENTHAL, NE MAZZOLA, P CHIUEH, CC HARDIN, T GARCIABORREGUERO, D SCHWARTZ, PJ TURNER, E OREN, DA MURPHY, DL TI PLATELET [H-3] PAROXETINE BINDING, 5-HT-STIMULATED CA2+ RESPONSE, AND 5-HT CONTENT IN WINTER SEASONAL AFFECTIVE-DISORDER SO BIOLOGICAL PSYCHIATRY LA English DT Article DE SEASONAL AFFECTIVE DISORDER; LIGHT THERAPY; SEROTONIN; PLATELET; CALCIUM; [H-3] PAROXETINE BINDING ID H-3 PAROXETINE BINDING; HUMAN-BLOOD PLATELETS; RECEPTOR-BINDING; SEROTONIN UPTAKE; DEPRESSED-PATIENTS; ANTIDEPRESSANT TREATMENT; H-3-IMIPRAMINE BINDING; BIPOLAR DEPRESSION; SUICIDE VICTIMS; FRONTAL-CORTEX AB The present study was designed to evaluate cellular serotonergic functions in winter seasonal affective disorder (SAD) using serotonin (5-HT)-stimulated Ca2+ response as an integrated measure of 5-HT2 receptor function in platelets, [H-3]paroxetine binding to characterize the platelet 5-HT transporter and 5-HT content as an index of the platelet storage capacity for this neurotransmitter amine. Purified density-dependent subpopulations of platelets in untreated and light-treated SAD patients and matched controls were investigated in order to control for possible variations in platelet turnover We found no differences between SAD patients and controls on any of the measures, nor between light therapy conditions in SAD patients, although We found a higher B-max of [H-3]paroxetine binding and 5-HT content in heavy platelets compared to light platelets. Although the validity of platelet serotonergic measures as a model for brain serotonergic systems still remains to be elucidated, we found no evidence of platelet serotonergic abnormalities in our sample of SAD patients. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RP OZAKI, N (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,BLDG 10,ROOM 4S-239,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Ozaki, Norio/M-8908-2014 OI Ozaki, Norio/0000-0002-7360-4898 NR 57 TC 32 Z9 32 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 1 PY 1994 VL 36 IS 7 BP 458 EP 466 DI 10.1016/0006-3223(94)90641-6 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA PJ339 UT WOS:A1994PJ33900005 PM 7811842 ER PT J AU KOZLOV, MM LEIKIN, S RAND, RP AF KOZLOV, MM LEIKIN, S RAND, RP TI BENDING, HYDRATION AND INTERSTITIAL ENERGIES QUANTITATIVELY ACCOUNT FOR THE HEXAGONAL-LAMELLAR-HEXAGONAL REENTRANT PHASE-TRANSITION IN DIOLEOYLPHOSPHATIDYLETHANOLAMINE SO BIOPHYSICAL JOURNAL LA English DT Article ID STRONGLY CURVED MONOLAYERS; HII PHASE; NEUTRAL SURFACE; ELASTIC-MODULI; DIFFRACTION; ENERGETICS; MEMBRANES; CURVATURE; SYSTEMS AB We have accounted for the unusual structural change wherein dioleoylphosphatidylethanolamine undergoes a hexagonal-lamellar-hexagonal transition sequence as the water content is reduced systematically. We describe the role played by the energies of bending, hydration, voids in hexagonal interstices, and van der Waals interaction in this transition sequence. We have used the x-ray diffraction and osmotic stress experiments on the two phases to derive the structural parameters and all of the force constants defining the energetics of the hexagonal and lamellar phases. We have calculated the chemical potentials of lipid and water in both phases and derived the phase diagram of the lipid with no free, adjustable parameters. The calculated temperature/osmotic stress and temperature/composition diagrams quantitatively agree with experiment. The reentrant transition appears to be driven by a delicate balance between the hydration energy in the lamellar phase and bending energy in the hexagonal phase, whereas the energy of voids in hexagonal interstices defines its energy scale and temperature range. Van der Waals attraction between the bilayers in the lamellar phase does not appear to be important in this transition. C1 NIDDKD,DIV COMP RES & TECHNOL,STRUCT BIOL LAB,BETHESDA,MD 20892. NIDDKD,DIV INTRAMURAL RES,BETHESDA,MD 20892. BROCK UNIV,DEPT SCI BIOL,ST CATHARINES,ON,CANADA. RP KOZLOV, MM (reprint author), FREE UNIV BERLIN,FB PHYS,WE2,ARNIMALLEE 14,D-14195 BERLIN,GERMANY. RI Leikin, Sergey/A-5518-2008 OI Leikin, Sergey/0000-0001-7095-0739 NR 20 TC 120 Z9 122 U1 3 U2 11 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD OCT PY 1994 VL 67 IS 4 BP 1603 EP 1611 PG 9 WC Biophysics SC Biophysics GA PJ131 UT WOS:A1994PJ13100024 PM 7819492 ER PT J AU ELLISON, J SQUIRES, G CRUTCHFIELD, C GOLDMAN, D AF ELLISON, J SQUIRES, G CRUTCHFIELD, C GOLDMAN, D TI DETECTION OF MUTATIONS AND POLYMORPHISMS USING FLUORESCENCE-BASED DIDEOXY FINGERPRINTING (F-DDF) SO BIOTECHNIQUES LA English DT Article ID POINT MUTATIONS; PCR-SSCP; DNA; SUBSTITUTIONS AB We have adapted the dideoxy fingerprinting (ddF) technique for detecting DNA sequence variants to fluorescence detection (F-ddF) using an Applied Biosystems Model 373A DNA Sequencer equipped with GENESCAN(TM) 672 software and an external temperature control device. The fingerprints can be precisely aligned using an internal standard run in the same lanes. This facilitates location and characterization of mobility changes resulting from sequence variants. As compared to fluorescence detected single-strand conformation polymorphism analysis (F-SSCP), F-ddF is equally efficient for detection of sequence variants, and it offers additional advantages. These include information regarding location of the sequence variation, greater reliability for distinguishing one sequence variant from another and the capacity to generate large PCR fragments and analyze them in smaller subsegments. Read length and overall quality of data from F-ddF are sequence-dependent when Taq DNA polymerase is used, but reducing terminator concentration can extend read length. The strengths and weakness of F-ddF and F-SSCP are different. Thus F-ddF may work better in a given situation than F-SSCP and vice versa. A strategy for using F-ddF to circumvent limitations of F-SSCP is described C1 NIAAA,BETHESDA,MD. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 13 TC 11 Z9 11 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 OCT PY 1994 VL 17 IS 4 BP 742 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PK379 UT WOS:A1994PK37900037 PM 7833039 ER PT J AU KELLER, JR BARTELMEZ, SH SITNICKA, E RUSCETTI, FW ORTIZ, M GOOYA, JM JACOBSEN, SEW AF KELLER, JR BARTELMEZ, SH SITNICKA, E RUSCETTI, FW ORTIZ, M GOOYA, JM JACOBSEN, SEW TI DISTINCT AND OVERLAPPING DIRECT EFFECTS OF MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA AND TRANSFORMING GROWTH-FACTOR-BETA ON HEMATOPOIETIC PROGENITOR STEM-CELL GROWTH SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; BONE-MARROW; FORMATION INVITRO; STEM-CELLS; MURINE; INVIVO; MOUSE; PROLIFERATION AB Both transforming growth factor P (TGF beta) and macrophage inflammatory protein 1 alpha (MIP-1 alpha) have been shown to be multifunctional regulators of hematopoiesis that can either inhibit or enhance the growth of hematopoietic progenitor cells (HPC). We report here the spectrum of activities of these two cytokines on different hematopoietic progenitor and stem cell populations, and whether these effects are direct or indirect. MIP-1 alpha enhances interleukin-3 (IL-3)/ and granulocyte-macrophage colony-stimulating factor (GM-CSF)/induced colony formation of normal bone marrow progenitor cells (BMC) and lineage-negative (Lin(-)) progenitors, but has no effect on G-CSF or CSF-1/induced colony formation. Similarly, TGF beta enhances GM-CSF/induced colony formation of normal BMC and Lin(-) progenitors. In contrast; TGF beta inhibits IL-3/ and CSF-1/induced colony formation of Lin(-) progenitors. The effects of MIP-1 alpha and TGF beta on the growth of Lin(-) progenitors were direct and correlate with colony formation in soft agar. Separation of the Lin(-) cells into Thy-1 and Thy-1(lo) subsets showed that the growth of Thy-1(lo) Lin(-) cells is directly inhibited by MIP-1 alpha and TGF beta regardless of the cytokine used to stimulate growth (IL-3, GM-CSF, or CSF-1). In contrast, two other stem cell populations (0% to 15% Hoechst 33342/Rhodamine 123 [Ho/Rh123] and Lin(-)Sca-1(+) cells) were markedly inhibited by TGF beta and unaffected by MIP-1 alpha. Furthermore, MIP-1 alpha has no effect on high proliferative potential colony-forming cells 1 or 2 (HPP-CFC/1 or /2) colony formation in vitro, whereas TGF beta inhibits both HPP-CFC/1 and HPP-CFC/2. Thus, MIP-1 alpha and TGF beta are direct bidirectional regulators of HPC growth, whose effects are dependent on other growth factors present as well as the maturational state of the HPC assayed. The spectrum of their inhibitory and enhancing activities shows overlapping yet distinct effects. (C) 1994 by The American Society of Hematology. C1 UNIV WASHINGTON,DEPT PATHOL,SEATTLE,WA 98195. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,LEUKOCYTE BIOL LAB,FREDERICK,MD 21702. NORWEGIAN RADIUM HOSP,INST CANC RES,DEPT IMMUNOL,OSLO,NORWAY. RP KELLER, JR (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,POB B,FREDERICK,MD 21702, USA. NR 22 TC 82 Z9 83 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 OCT 1 PY 1994 VL 84 IS 7 BP 2175 EP 2181 PG 7 WC Hematology SC Hematology GA PK125 UT WOS:A1994PK12500014 PM 7919333 ER PT J AU MACKALL, CL FLEISHER, TA BROWN, MR MAGRATH, IT SHAD, AT HOROWITZ, ME WEXLER, LH ADDE, MA MCCLURE, LL GRESS, RE AF MACKALL, CL FLEISHER, TA BROWN, MR MAGRATH, IT SHAD, AT HOROWITZ, ME WEXLER, LH ADDE, MA MCCLURE, LL GRESS, RE TI LYMPHOCYTE DEPLETION DURING TREATMENT WITH INTENSIVE CHEMOTHERAPY FOR CANCER SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; PNEUMOCYSTIS-CARINII PNEUMONIA; BONE-MARROW TRANSPLANTATION; ADJUVANT CHEMOTHERAPY; BREAST-CANCER; BLOOD; NEUTROPENIA; INFECTION; THERAPY; REGENERATION AB Recently we have observed an increased incidence of opportunistic infections in patients treated with intensive chemotherapy for cancer. Because T-cell depletion is associated with similar clinical events in human immunodeficiency virus infection and after bone marrow transplantation, we have analyzed peripheral blood lymphocyte populations in a series of patients during treatment with intensive chemotherapy for cancer. Although neutrophil, monocyte, and platelet numbers consistently recovered to greater than 50% of pretreatment values after each sequential cycle of therapy, lymphocyte numbers did not recover within the same time period. B cells decreased rapidly from a mean value of 149 +/- 46/mm(3) before chemotherapy to 4 +/- 1/mm(3) during chemotherapy (P =.01). CD4(+) T cells decreased from a mean of 588 +/- 76/mm(3) before chemotherapy to 105 +/- 28/mm(3) during chemotherapy (P =.0002) and CD8(+) T cells decreased from a mean of 382 +/- 41/mm(3) before chemotherapy to 150 +/- 46/mm(3) during chemotherapy (P =.0009). Natural killer cell numbers did not show significant declines (171 +/- 30/ mm(3) before, 114 +/- 24/mm(3) during, P =.19). Based on the history of opportunistic complications in patients with other disorders who display similar degrees of CD4(+) T-cell lymphopenia and preliminary observations in this population, immune incompetence could surface as a dose-limiting toxicity for highly dose-intensive chemotherapy regimens. C1 NCI,DIV CANC TREATMENT,PEDIAT BRANCH,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT CLIN PATHOL,BETHESDA,MD 20892. RP MACKALL, CL (reprint author), NCI,DIV CANC BIOL DIAG & CTR,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B14,BETHESDA,MD 20892, USA. NR 33 TC 247 Z9 251 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 OCT 1 PY 1994 VL 84 IS 7 BP 2221 EP 2228 PG 8 WC Hematology SC Hematology GA PK125 UT WOS:A1994PK12500021 PM 7919339 ER PT J AU DATTA, AR BARRETT, AJ JIANG, YZ GUIMARAES, A MAVROUDIS, DA VANRHEE, F GORDON, AA MADRIGAL, A AF DATTA, AR BARRETT, AJ JIANG, YZ GUIMARAES, A MAVROUDIS, DA VANRHEE, F GORDON, AA MADRIGAL, A TI DISTINCT T-CELL POPULATIONS DISTINGUISH CHRONIC MYELOID-LEUKEMIA CELLS FROM LYMPHOCYTES IN THE SAME INDIVIDUAL - A MODEL FOR SEPARATING GVHD FROM GVL REACTIONS SO BONE MARROW TRANSPLANTATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; GRAFT-VERSUS-LEUKEMIA; MINOR HISTOCOMPATIBILITY ANTIGENS; CHRONIC MYELOGENOUS LEUKEMIA; DONOR LEUKOCYTE INFUSIONS; HOST DISEASE; FREQUENCY; RELAPSE; ELIMINATION; PRECURSORS AB Donor lymphocyte responses to minor histocompatibility antigen (mHA) differences are involved in alloresponses between HLA matched pairs causing GVHD and graft-versus-leukaemia (GVL). Since some mHA are tissue-restricted, GVHD and GM, responses may be separable. We studied donor lymphocyte responses to patients with CML in a series of 10 HLA-matched sibling and 10 unrelated donor-recipient pairs comparing proliferation to recipient PHA blasts and CML cells and attempting to selectively deplete responses to PHA blasts in vitro. Responses in counts per min (c.p.m) to CML cells and PHA blasts were, respectively, 2809 +/- 2205 (SD) and 7376 +/- 1877 in related and 12107 +/- 7191 and 26136 +/- 22479 in unrelated pairs. Autologous responses to PHA blasts were significantly lower (mean 779 +/- 735) (p < 0.001). Results correlated with clinical outcome: higher responses to recipient cells correlated with transplant-related death (p = 0.02 for CR(IL and p = 0.06 for PHA blasts). Higher responses to CML correlated with GVHD grade greater than or equal to II (p = 0.025). Donor lymphocytes exposed to recipient PHA blasts for 5 days and treated with a ricin-conjugated anti-CD25 antibody retained over 75% of their response to CML but < 10% to PHA blasts. Similarly, depletion of response to CML but not to PHA blasts occurred when CML was the primary challenge. These results indicate that distinct populations of donor T cells respond to recipient leukaemic and non-leukaemic cells, and provide the basis for a clinically applicable technique to selectively deplete donor GVHD reacting cells while conserving GVL. C1 NHLBI,HEMATOL BRANCH,BONE MARROW TRANSPLANT UNIT,BETHESDA,MD 20892. ROYAL POSTGRAD MED SCH,DEPT HAEMATOL,LONDON W12 0HS,ENGLAND. ROYAL FREE HOSP,ANTHONY NOLAN RES LABS,LONDON NW3 2QG,ENGLAND. NR 30 TC 60 Z9 61 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD OCT PY 1994 VL 14 IS 4 BP 517 EP 524 PG 8 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA PP757 UT WOS:A1994PP75700004 PM 7858526 ER PT J AU KATSANIS, E XU, Z ANDERSON, PM DANCISAK, BB BAUSERO, MA WEISDORF, DJ BLAZAR, BR OCHOA, AC AF KATSANIS, E XU, Z ANDERSON, PM DANCISAK, BB BAUSERO, MA WEISDORF, DJ BLAZAR, BR OCHOA, AC TI SHORT-TERM EX-VIVO ACTIVATION OF SPLENOCYTES WITH ANTI-CD3 PLUS IL-2 AND INFUSION POST-BMT INTO MICE RESULTS IN IN-VIVO EXPANSION OF EFFECTOR-CELLS WITH POTENT ANTI-LYMPHOMA ACTIVITY SO BONE MARROW TRANSPLANTATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; VERSUS-HOST DISEASE; ACUTE LYMPHOBLASTIC-LEUKEMIA; KILLER-CELLS; RECOMBINANT INTERLEUKIN-2; T-CELLS; MYELOGENOUS LEUKEMIA; LIPOSOMES; PHASE; MODEL AB We investigated the proliferation and therapeutic utility of anti-CD3 activated splenocytes infused into mice following BMT. Using congenic mouse strains we demonstrated that splenocytes activated briefly ex vivo with anti-CD3 plus IL-2 (T-activated killer cells or T-AK) and infused intravenously following BMT had a greater expansion in blood, spleen and BM compared with splenocytes stimulated with IL-2 alone. T-AK cells recovered from blood, spleen and BM consisted predominantly of CD8(+) T cells. A single infusion of T-AK cells given on day +1 post-syngeneic BMT and sustained in vivo with liposomal encapsulated IL-2, significantly increased survival of mice with BDL-2 lymphoma when compared with mice receiving saline and those treated with IL-2 liposomes alone. The anti-tumor effect of T-AK cells was significantly enhanced when IL-2 was given by continuous infusion compared with bolus injections. Depletion studies confirmed that the CD8(+) T-AK cells were mainly responsible for the anti-tumor effect against BDL-2 lymphoma. Our findings demonstrate that brief ex vivo activation of splenocytes with anti-CD3 plus IL-2 results in in vivo proliferation of effector cells with potent anti-tumor activity following BMT. C1 UNIV MINNESOTA,DEPT MED,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,BONE MARROW TRANSPLANT PROGRAM,MINNEAPOLIS,MN 55455. INC DYN CORP,NATL CANC INST,PROGRAM RESOURCES,FREDERICK,MD. RP KATSANIS, E (reprint author), UNIV MINNESOTA,DEPT PEDIAT,BOX 484,420 DELAWARE ST SE,MINNEAPOLIS,MN 55455, USA. FU NCI NIH HHS [P01-CA-21737]; NIAID NIH HHS [N01-AI-85002] NR 32 TC 11 Z9 13 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD OCT PY 1994 VL 14 IS 4 BP 563 EP 572 PG 10 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA PP757 UT WOS:A1994PP75700009 PM 7858530 ER PT J AU KUIJPERS, GAJ VERGARA, LA CALVO, S YADID, G AF KUIJPERS, GAJ VERGARA, LA CALVO, S YADID, G TI INHIBITORY EFFECT OF STRYCHNINE ON ACETYLCHOLINE-RECEPTOR ACTIVATION IN BOVINE ADRENAL-MEDULLARY CHROMAFFIN CELLS SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE STRYCHNINE; ACETYLCHOLINE; GLYCINE; NICOTINE; GLYCINE RECEPTOR; CHROMAFFIN, SECRETION; NICOTINIC ACH RECEPTOR ID RAT SPINAL-CORD; GLYCINE RECEPTOR; FUNCTIONAL EXPRESSION; SODIUM CONDUCTANCE; FROG NODE; BINDING; NEURONS; SECRETION; RESPONSES; MEMBRANES AB 1 Strychnine, which is known as a potent and selective antagonist of the inhibitory glycine receptor in the central nervous system, inhibits the nicotinic stimulation of catecholamine release from bovine cultured adrenal chromaffin cells in a concentration-dependent (1-100 mu M) manner. At 10 mu M nicotine, the IC50 value for strychnine is approximately 30 mu M. Strychnine also inhibits the nicotine-induced membrane depolarization and increase in intracellular Ca2+ concentration. 2 The inhibitory action of strychnine is reversible and is selective for nicotinic stimulation, with no effect observed on secretion elicited by a high external K+ concentration, histamine or angiotensin II. 3 Strychnine competes with nicotine in its effect, but does not modify the apparent positive cooperativity of the nicotine binding sites. In the absence of nicotine, strychnine has no effect on catecholamine release. Glycine does not affect catecholamine release nor the inhibitory action of strychnine on this release, 4 These results suggest that strychnine interacts with the agonist binding site of the nicotinic acetylcholine receptor in chromaffin cells, thus exerting a pharmacological effect independently of the glycine receptor. C1 BAR ILAN UNIV,DEPT LIFE SCI,IL-55900 RAMAT GAN,ISRAEL. NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892. NR 51 TC 8 Z9 8 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD OCT PY 1994 VL 113 IS 2 BP 471 EP 478 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PH434 UT WOS:A1994PH43400026 PM 7834198 ER PT J AU PEOPLES, RW WEIGHT, FF AF PEOPLES, RW WEIGHT, FF TI TRICHLOROETHANOL POTENTIATION OF GAMMA-AMINOBUTYRIC ACID-ACTIVATED CHLORIDE CURRENT IN MOUSE HIPPOCAMPAL-NEURONS SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE GABA(A) RECEPTOR; TRICHLOROETHANOL; ANESTHETIC; HIPPOCAMPAL NEURONS; CHLORIDE CURRENT; MEMBRANE ION CURRENT; ALCOHOL; RECEPTOR MODULATION; NEUROTRANSMITTER RECEPTOR ID SPINAL-CORD NEURONS; GABA-A RECEPTORS; SENSORY NEURONS; POSTSYNAPTIC CURRENTS; SUBUNIT COMPOSITION; INVERSE AGONISTS; GANGLION NEURONS; CEREBRAL-CORTEX; CHANNEL COMPLEX; TISSUE-CULTURE AB 1 The action of 2,2,2-trichloroethanol on gamma-aminobutyric acid (GABA)-activated Cl- current was studied in mouse hippocampal neurones in tissue culture by use of whole-cell patch-clamp recording. 2 Trichloroethanol increased the amplitude of currents activated by 1 mu M GABA or 0.1 mu M muscimol. Trichloroethanol, 1-25 mM, potentiated current activated by 1 mu M GABA in a concentration-dependent manner with an EC(50) of 3.0 +/- 1.4 mM and a maximal response (E(max)) of 576+/-72% of control. 3 Trichloroethanol potentiated currents activated by GABA concentrations <1O mu M, but did not increase the amplitude of currents activated by concentrations of GABA greater than or equal to 10 mu M. Despite marked potentiation of currents activated by low concentrations of GABA, trichloroethanol did not significantly alter the EC(50), slope, or E(max) of the GABA concentration-response curve. 4 Trichloroethanol, 5 mM, potentiated GABA-activated current in neurones in which ethanol, 10-500 mM, did not. The effect of trichloroethanol was not altered by the putative ethanol antagonist, Ro 15-4513. Trichloroethanol did not potentiate currents activated by pentobarbitone. 5 In the absence of exogenous GABA, trichloroethanol at concentrations greater than or equal to 2.5mM activated a current that appeared to be carried by Cl- as its reversal potential changed with changes in the Cl- gradient and as it was inhibited by the GABA(A) antagonists, bicuculline methiodide and picrotoxin. 6 Since trichloroethanol is thought to be the active metabolite of chloral hydrate and other chloral derivative anaesthetics, potentiation of the GABA-activated current in central nervous system neurones by trichloroethanol may contribute to the sedative/hypnotic effects of these agents. C1 NIAAA, MOLEC & CELLULAR NEUROBIOL LAB, BETHESDA, MD 20892 USA. NR 66 TC 41 Z9 41 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD OCT PY 1994 VL 113 IS 2 BP 555 EP 563 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PH434 UT WOS:A1994PH43400038 PM 7834208 ER PT J AU BOYER, JL ZOHN, IE JACOBSON, KA HARDEN, TK AF BOYER, JL ZOHN, IE JACOBSON, KA HARDEN, TK TI DIFFERENTIAL-EFFECTS OF P-2-PURINOCEPTOR ANTAGONISTS ON PHOSPHOLIPASE C-COUPLED AND ADENYLYL CYCLASE-COUPLED P-2Y-PURINOCEPTORS SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE REACTIVE BLUE 2; SURAMIN; PPADS; PHOSPHOLIPASE C; INOSITOL PHOSPHATES; P-2Y-PURINOCEPTORS; CYCLIC AMP ACCUMULATION; ADENYLYL CYCLASE INHIBITION; C6 RAT GLIOMA CELLS ID TURKEY ERYTHROCYTE-MEMBRANES; SIGNAL TRANSDUCTION SYSTEMS; AORTIC ENDOTHELIAL-CELLS; G-PROTEIN; P2-PURINERGIC RECEPTORS; EXTRACELLULAR ATP; REACTIVE BLUE-2; GUINEA-PIG; MEDIATED ACTIVATION; MOLECULAR-CLONING AB 1 Stimulation of P-2Y-purinoceptors on turkey erythrocytes and many other cell types results in activation of phospholipase C. In contrast, we have observed recently that P-2Y-purinoceptors on C6 rat glioma cells are not coupled to phospholipase C, but rather, inhibit adenylyl cyclase. 2 In this study we investigated the pharmacological selectivity of the P-2-purinoceptor antagonists, suramin, reactive blue 2, and pyridoxal phosphate 6-azophenyl 2',4'-disulphonic acid (PPADS) for phospholipase C- and adenylyl cyclase-coupled P-2Y-purinoceptors. 3 In C6 glioma cells, suramin and reactive blue 2 competitively antagonized the inhibitory effect of 2MeSATP on adenylyl cyclase (pK(B) = 5.4 +/- 0.2 and 7.6 +/- 0.1, respectively), whereas PPADS at concentrations up to 100 mu M had no effect. 4 In contrast, in the turkey erythrocyte preparation, PPADS at concentrations up to 30 mu M was a competitive antagonist of P-2Y-purinoceptor-stimulated phospholipase C activity (pK(B) = 5.9 +/- 0.1). Suramin and reactive blue 2 produced both a shift to the right of the concentration-effect of 2MeSATP for the activation of phospholipase C and a significant decrease in the maximal inositol phosphate response. 5 Turkey erythrocytes also express a phospholipase C-coupled beta-adrenoceptor. Concentrations of PPADS that competitively inhibited the P-2Y-purinoceptor-mediated response had only minimal effects on the activation of phospholipase C by beta-adrenoceptors. In contrast, suramin and reactive blue 2 produced a non-competitive inhibition, characterized by decreases in the maximal response to isoprenaline with no change in the potency of this beta-adrenoceptor agonist. 6 The differential effect of PPADS on P-2Y-purinoceptors of C6 glioma cells and turkey erythrocytes adds further support to the idea that different P-2Y-purinoceptor subtypes mediate coupling to adenylyl cyclic and phospholipase C. C1 UNIV N CAROLINA,SCH MED,DEPT PHARMACOL,CHAPEL HILL,NC 27599. NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031116-20, Z99 DK999999]; NHLBI NIH HHS [HL 32322]; NIGMS NIH HHS [GM 29563, GM 38213] NR 50 TC 116 Z9 119 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD OCT PY 1994 VL 113 IS 2 BP 614 EP 620 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PH434 UT WOS:A1994PH43400047 PM 7834215 ER PT J AU AZNAVOORIAN, SA LIOTTA, LA AF AZNAVOORIAN, SA LIOTTA, LA TI MOLECULAR-BASIS OF CANCER INVASION SO BULLETIN DE L INSTITUT PASTEUR LA English DT Article ID EXTRACELLULAR-MATRIX; TUMOR-METASTASIS; TISSUE INHIBITOR; BREAST-CANCER; GROWTH CONES; CELLS; PROGRESSION; EXPRESSION; PROTEIN; METALLOPROTEINASE C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NR 59 TC 1 Z9 1 U1 1 U2 1 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0020-2452 J9 B I PASTEUR JI Bull. Inst. Pasteur PD OCT-DEC PY 1994 VL 92 IS 4 BP 234 EP 241 PG 8 WC Immunology; Microbiology; Virology SC Immunology; Microbiology; Virology GA QB727 UT WOS:A1994QB72700004 ER PT J AU SAVAGE, SA KOHN, EC AF SAVAGE, SA KOHN, EC TI CALCIUM SIGNAL-TRANSDUCTION TARGETS IN INVASION AND METASTASIS SO BULLETIN DE L INSTITUT PASTEUR LA English DT Article ID CELL LUNG-CANCER; INOSITOL PHOSPHATES; CA2+ INFLUX; TUMOR-CELLS; EXPRESSION; ACTIVATION; GELSOLIN; MECHANISM; MOTILITY; CHANNELS C1 NIH,PATHOL LAB,SIGNAL TRANSDUCT & PREVENT UNIT,BETHESDA,MD 20892. RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 NR 63 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0020-2452 J9 B I PASTEUR JI Bull. Inst. Pasteur PD OCT-DEC PY 1994 VL 92 IS 4 BP 259 EP 269 PG 11 WC Immunology; Microbiology; Virology SC Immunology; Microbiology; Virology GA QB727 UT WOS:A1994QB72700008 ER PT J AU ISRAEL, L LIOTTA, L RUOSLAHTI ALBINO, AP SCHWARTZ, GK REED, JA SASTREGARAU GARBISA, S YOKOTA KERBEL SAVAGE KOHN, EC BARLATI, S ZUCKER, S AF ISRAEL, L LIOTTA, L RUOSLAHTI ALBINO, AP SCHWARTZ, GK REED, JA SASTREGARAU GARBISA, S YOKOTA KERBEL SAVAGE KOHN, EC BARLATI, S ZUCKER, S TI METASTASES - 1ST FORUM IN THE BULLETIN DE LINSTITUT PASTEUR - DISCUSSION SO BULLETIN DE L INSTITUT PASTEUR LA English DT Discussion DE METASTASIS; FORUM C1 NCI,PATHOL LAB,BETHESDA,MD 20892. LA JOLLA CANC RES FDN,LA JOLLA,CA 92037. MEM SLOAN KETTERING CANC CTR,MAMMALIAN CELL TRANSFORMAT LAB,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,DIV SOLID TUMOR ONCOL,GASTROINTESTINAL ONCOL SECT,NEW YORK,NY 10021. NEW YORK HOSP,CORNELL MED CTR,DEPT PATHOL,DIV DERMATOPATHOL,NEW YORK,NY. NEW YORK HOSP,CORNELL MED CTR,DEPT DERMATOL,DIV DERMATOPATHOL,NEW YORK,NY. INST CURIE,PATHOL LAB,F-75231 PARIS 05,FRANCE. UNIV PADUA,INST HISTOL & GEN EMBRYOL,I-35121 PADUA,ITALY. NATL CANC CTR,RES INST,CHUO KU,TOKYO 104,JAPAN. SUNNYBROOK HLTH SCI CTR,DIV CANC RES,TORONTO,ON M4N 3M5,CANADA. UNIV TORONTO,DEPT MED BIOPHYS,TORONTO,ON,CANADA. NIH,PATHOL LAB,SIGNAL TRANSDUCT & PREVENT UNIT,BETHESDA,MD 20892. DEPT BIOMED SCI & BIOTECHNOL,DIV BIOL & GENET,I-25123 BRESCIA,ITALY. DEPT VET AFFAIRS MED CTR,DEPT MED,NORTHPORT,NY 11768. DEPT VET AFFAIRS MED CTR,DEPT RES,NORTHPORT,NY 11768. SUNY STONY BROOK,STONY BROOK,NY 11794. TUFTS UNIV,SCH MED,DEPT ANAT & CELL BIOL,BOSTON,MA 02111. RP ISRAEL, L (reprint author), UNIV PARIS 13,CHU AVICENNE,CANCEROL CLIN,BOBIGNY 93,FRANCE. RI Barlati, Sergio/A-2666-2010 NR 3 TC 0 Z9 0 U1 0 U2 2 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0020-2452 J9 B I PASTEUR JI Bull. Inst. Pasteur PD OCT-DEC PY 1994 VL 92 IS 4 BP 299 EP 312 PG 14 WC Immunology; Microbiology; Virology SC Immunology; Microbiology; Virology GA QB727 UT WOS:A1994QB72700014 ER PT J AU LACROIX, EM AF LACROIX, EM TI INTERLIBRARY LOAN IN UNITED-STATES HEALTH-SCIENCES LIBRARIES - JOURNAL ARTICLE USE SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article ID NATIONAL-LIBRARY; MEDICINE; SERVICE AB Health sciences libraries in the United States use the National Library of Medicine (NLM) DOCLINE(R) system to request more than two million items annually through interlibrary loan (ILL). Ninety-seven percent of all ILL requests are for journal articles. In this study, NLM analyzed four million ILL requests entered into the DOCLINE system during two twelve-month periods ending September 30, 1992. The requests were analyzed at both the journal title level and article level. Data for the two years were found to be remarkably similar. Results showed that a large number of journals are required to fill ILL requests and that there is a relatively low number of repeat requests for most journal articles. Seventy-six percent of journal articles analyzed were requested only once, and fewer than 1% were requested more than ten times. About 39% of journals used to fill ILL requests were indexed in MEDLINE(R) at some time, while 84% of the articles supplied were indexed in MEDLINE. Ninety-two percent of articles supplied were from English-language journals. Sixty-seven percent of articles were published in the most recent five years, and 85% in the most recent ten years. The 100 most frequently requested articles for each of the two years were examined to determine characteristics such as language, where they were indexed, and the subject matter. This study has provided valuable information for planning of NLM's interlibrary document delivery services and also should have significance for libraries and other organizations involved in document delivery. RP LACROIX, EM (reprint author), NATL LIB MED,8600 ROCKVILLE PIKE,BETHESDA,MD 20209, USA. NR 9 TC 10 Z9 11 U1 0 U2 1 PU MED LIBRARY ASSN PI CHICAGO PA SUITE 300 6 N MICHIGAN AVE, CHICAGO, IL 60602 SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD OCT PY 1994 VL 82 IS 4 BP 363 EP 368 PG 6 WC Information Science & Library Science SC Information Science & Library Science GA PN105 UT WOS:A1994PN10500002 PM 7841903 ER PT J AU CORN, M JOHNSON, FE AF CORN, M JOHNSON, FE TI CONNECTING THE HEALTH-SCIENCES COMMUNITY TO THE INTERNET - THE NLM/NSF GRANT PROGRAM SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article AB In 1992, as part of its high-performance computing and communications initiative, the National Library of Medicine decided to provide health sciences institutions with Internet connection grants similar to those offered to universities by the National Science Foundation. Although library involvement is not required, librarian and library uses have been the most common category in the applications received. RP CORN, M (reprint author), NATL LIB MED,EXTRAMURAL PROGRAMS,BETHESDA,MD 20209, USA. NR 1 TC 8 Z9 8 U1 0 U2 0 PU MED LIBRARY ASSN PI CHICAGO PA SUITE 300 6 N MICHIGAN AVE, CHICAGO, IL 60602 SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD OCT PY 1994 VL 82 IS 4 BP 392 EP 395 PG 4 WC Information Science & Library Science SC Information Science & Library Science GA PN105 UT WOS:A1994PN10500008 PM 7841908 ER PT J AU LACROIX, EM BACKUS, JEB LYON, BJ AF LACROIX, EM BACKUS, JEB LYON, BJ TI SERVICE PROVIDERS AND USERS DISCOVER THE INTERNET SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article AB Although the Internet has evolved over more than twenty years, resources useful to health information professionals have become available on the Internet only recently. A survey conducted by the Regional Medical Libraries of the National Network of Libraries of Medicine in the fall of 1993 indicates that libraries at academic institutions are much more likely to have access to the Internet (72%) than are libraries in hospital environments (24%). Health information professionals who take on the challenge and exploit the Internet's resources find rewards for themselves and their clients. The basic electronic mail capability of the Internet allows colleagues to collaborate, communicate, and participate in daily continuing education. Internet terminal and file-transfer capabilities provide improved access to traditional resources and first-time access to new electronic resources. Through the Internet, online catalogs are available worldwide, and document delivery is faster, cheaper, and more reliable than ever before. Institutions can make organizational, full-text, online, and publication information available through Internet tools such as direct file-transfer protocol (FTP), menu-based Gopher, and hypertext-based Mosaic. The National Library of Medicine (NLM) is among organizations finding new ways to provide service through the Internet. NLM now uses electronic mail to communicate with users, FTP service to distribute publications, and tools such as Gopher and Mosaic to distribute publications and graphics and connect users to online services. The Internet allows service providers and health sciences information professionals to work in a rich, new medium whose potential is just beginning to be explored. At the same time, its characteristics-including lack of formal organization, standards, quality control, and permanence-pose a challenge. C1 NATL LIB MED,DIV PUBL SERV,BETHESDA,MD 20894. RP LACROIX, EM (reprint author), NATL LIB MED,DIV PUBL SERV,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 14 TC 22 Z9 22 U1 0 U2 2 PU MED LIBRARY ASSN PI CHICAGO PA SUITE 300 6 N MICHIGAN AVE, CHICAGO, IL 60602 SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD OCT PY 1994 VL 82 IS 4 BP 412 EP 418 PG 7 WC Information Science & Library Science SC Information Science & Library Science GA PN105 UT WOS:A1994PN10500012 PM 7841912 ER PT J AU HENSON, DE MENCK, HR AF HENSON, DE MENCK, HR TI THE NATIONAL CANCER DATA-BASE REPORT ON TRENDS IN CANCER-PATIENT STAGING SO CANCER LA English DT Article DE CANCER; STAGING; NATIONAL CANCER DATA BASE; QUALITY OF CARE; HOSPITAL PRACTICES ID FUTURE-DIRECTIONS; SOLID TUMORS; CLASSIFICATION; PROGNOSIS; MYC AB Background. Previous Commission on Cancer studies have examined trends in the staging of cancer patients. Reported herein are the most current National Cancer Data Base (NCDB) data on staging. Methods. Two ''calls for data'' have yielded a total of 770,100 reports of patients with cancer eligible for staging. Results. For all stageable sites combined, the percentage of cases with documentation of staging increased from 1985 through 1990 (53% in 1985 vs. 77% in 1990). Cancers of the colon and breast were staged most frequently. Of the 837 NCDB-participating hospitals, 557 (67%) staged 80% or more of the patients with cancer. Conclusions. These results suggest that the frequency of staging is a function of hospitals rather than physicians or types of patients. Many interrelated factors contributed to the increase in the frequency of staging. C1 AMER COLL SURG,DEPT CANC,COMMISS CANC,CHICAGO,IL 60611. NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT BRANCH,BETHESDA,MD 20892. NR 19 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD OCT 1 PY 1994 VL 74 IS 7 BP 1974 EP 1978 DI 10.1002/1097-0142(19941001)74:7<1974::AID-CNCR2820740724>3.0.CO;2-0 PG 5 WC Oncology SC Oncology GA PH625 UT WOS:A1994PH62500023 PM 8082104 ER PT J AU YANCIK, R RIES, LA AF YANCIK, R RIES, LA TI CANCER IN OLDER PERSONS - MAGNITUDE OF THE PROBLEM - HOW DO WE APPLY WHAT WE KNOW SO CANCER LA English DT Article; Proceedings Paper CT National Conference on Cancer and the Older Person CY FEB 10-12, 1994 CL ATLANTA, GA DE CANCER; ELDERLY; AGING; INCIDENCE; MORTALITY AB The elderly experience the major impact of cancer. The incidence rate for those aged 65 and older is 2085.3 per 100,000 as compared with 193.9 per 100,000 for those younger than 65. Overall, 58% of all cancer incidence is in the older segment of the population. Cancer mortality in the elderly now accounts for 67% of all cancer deaths. Data from the National Cancer Institute Surveillance, Epidemiology, and End Results program for 1985-1989 reveal many salient facts, Older persons have a risk of developing cancer 10 times greater than that for individuals younger than 65. This paper outlines the magnitude of the major cancers that affect the elderly. Incidence and mortality data are presented according to individual tumors (colon, rectum, lung/bronchus, pancreas, stomach, urinary bladder, breast, ovary, and prostate). Demographic data from the U.S. Bureau of the Census focus on the expanding elderly population in the United States and projections for the future. Needs for cancer care and treatment for the elderly, already great, are likely to increase. It is imperative that older persons receive special attention for cancer prevention, early diagnosis, and treatment efforts, especially because there is almost always an overlay of other chronic diseases and age-associated declines concurrent with the diagnosis of cancer in the elderly. This paper highlights issues unique to older persons as individuals at high risk for cancer and suggests research strategies that should be made in anticipation of the even greater cancer burden for the elderly as this subset of the population expands. C1 NCI,DIV CANC PREVENT & CONTROL,CANC STAT BRANCH,SURVEILLANCE PROGRAM,BETHESDA,MD 20892. RP YANCIK, R (reprint author), NIA,OFF DIRECTOR,BLDG 31,ROOM 5C05,31 CTR DR MSC 2292,BETHESDA,MD 20892, USA. NR 22 TC 126 Z9 129 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD OCT 1 PY 1994 VL 74 IS 7 SU S BP 1995 EP 2003 DI 10.1002/1097-0142(19941001)74:7+<1995::AID-CNCR2820741702>3.0.CO;2-Y PG 9 WC Oncology SC Oncology GA PJ094 UT WOS:A1994PJ09400001 PM 8087762 ER PT J AU HAVLIK, RJ YANCIK, R LONG, S RIES, L EDWARDS, B AF HAVLIK, RJ YANCIK, R LONG, S RIES, L EDWARDS, B TI THE NATIONAL-INSTITUTE-ON-AGING AND THE NATIONAL-CANCER-INSTITUTE SEER COLLABORATIVE STUDY ON COMORBIDITY AND EARLY DIAGNOSIS OF CANCER IN THE ELDERLY SO CANCER LA English DT Article; Proceedings Paper CT National Conference on Cancer and the Older Person CY FEB 10-12, 1994 CL ATLANTA, GA DE MEDICAL ONCOLOGY; AGING; CANCER STAGE; CHRONIC DISEASE ID OLDER PERSON; DISEASE; BREAST; AGE AB Background. An effect of comorbidity, or the coexistence of other diseases, on the stage of cancer at diagnosis and the appropriateness of therapy in older patients with cancer is hypothesized. The effect of comorbidity differs by cancer site and by type of comorbidity. Such variation could be due to the use of different populations or methods, or the natural history of the tumor being studied. Methods. The National Institute on Aging (NIA) and the National Cancer Institute (NCI) have initiated a study using cancer patient populations in the NCI's SEER (Surveillance, Epidemiology and End Results) program. Five geographic locations participated in the NIA/NCI pilot study of comorbidity associated with seven cancer sites. Approximately 250 patients with each type of cancer, stratified by age (either 65-74 years of age or 75 years and older) had hospital records abstracted for comorbidity using a form derived from previously reported methods. Results. After analyzing preliminary results for 1712 patients, it was ascertained that more and different chronic disease categories would be necessary, that it was not feasible to collect data on ability to perform certain physical functions from the medical records, and that the collection of data on current medications was possible. With these limitations, relationships of comorbid conditions with stage of cancer were analyzed. Conclusion. With the success of the pilot study, the full study is underway. In addition to the planned abstracting of approximately 7800 records, interviews assessing the behavior of illness in a sample of 1000 cancer patients will provide valuable information on the influence of comorbidity and age on stage at initial diagnosis and the treatment of older persons afflicted with cancer. C1 NCI,BETHESDA,MD. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. RP HAVLIK, RJ (reprint author), NIA,GATEWAY BLDG 3C309,BETHESDA,MD 20892, USA. NR 17 TC 143 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 0008-543X J9 CANCER JI Cancer PD OCT 1 PY 1994 VL 74 IS 7 SU S BP 2101 EP 2106 DI 10.1002/1097-0142(19941001)74:7+<2101::AID-CNCR2820741718>3.0.CO;2-M PG 6 WC Oncology SC Oncology GA PJ094 UT WOS:A1994PJ09400017 PM 8087777 ER PT J AU SUTTON, SM EISNER, EJ BURKLOW, J AF SUTTON, SM EISNER, EJ BURKLOW, J TI HEALTH COMMUNICATIONS TO OLDER AMERICANS AS A SPECIAL POPULATION - THE NATIONAL-CANCER-INSTITUTE CONSUMER-BASED APPROACH SO CANCER LA English DT Article; Proceedings Paper CT National Conference on Cancer and the Older Person CY FEB 10-12, 1994 CL ATLANTA, GA DE OLDER AMERICANS; ELDERLY; CANCER SCREENING; EARLY DETECTION; FEAR; BARRIERS; BENEFITS; HEALTH COMMUNICATIONS AB Background. Focus groups conducted by the National Cancer Institute in 1990 revealed that a multitude of fears, anxieties, and negative perceptions underlie the attitudes and behaviors of older Americans with respect to cancer. This central finding suggested that a communications approach aimed at encouraging cancer screening and early detection behavior among older Americans would need to consider the pervasiveness of these fears and not focus on health benefits alone. Methods. To explore consumer reactions to a new fear acknowledgment/self-empowerment communications strategy, three alternative positioning ads (or concepts) reflecting the strategy were prepared and evaluated through 29 in-depth interviews with members of the target audience. Results. Results confirmed the underlying fear of cancer found in earlier focus groups, a step which was critical for assessing the general strategic approach embodied in the ads. The idea that older people operate from a base of widespread fear and need to be empowered to take charge of their health resonates with and makes sense to the intended audience. A single ad concept was developed from the original three that reflects the feedback of the interviewees. Conclusions. Using the approach of fear acknowledgment/self-empowerment with older Americans is likely to affect the target audience positively. As a whole, respondents in the study considered the ads that embodied this strategy to be empathetic, helpful, and easy to relate to. C1 NCI,OFF CANC COMMUN,BETHESDA,MD 20892. NR 9 TC 2 Z9 2 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 OCT 1 PY 1994 VL 74 IS 7 SU S BP 2194 EP 2199 DI 10.1002/1097-0142(19941001)74:7+<2194::AID-CNCR2820741734>3.0.CO;2-E PG 6 WC Oncology SC Oncology GA PJ094 UT WOS:A1994PJ09400033 PM 8087791 ER PT J AU TRIMBLE, EL CARTER, CL CAIN, D FREIDLIN, B UNGERLEIDER, RS FRIEDMAN, MA AF TRIMBLE, EL CARTER, CL CAIN, D FREIDLIN, B UNGERLEIDER, RS FRIEDMAN, MA TI REPRESENTATION OF OLDER PATIENTS IN CANCER-TREATMENT TRIALS SO CANCER LA English DT Article; Proceedings Paper CT National Conference on Cancer and the Older Person CY FEB 10-12, 1994 CL ATLANTA, GA DE NEOPLASMS; CANCER; ELDERLY; CLINICAL TRIALS; INCIDENCE RATES ID OVARIAN-CANCER; CHEMOTHERAPY; EXPERIENCE AB In 1990, the five leading causes of cancer death in men aged 65 and older were carcinomas of the lung, prostate, colon and rectum, and pancreas, and leukemia. For women in this age group, the five leading causes of cancer death were carcinomas of the lung, breast, colon and rectum, pancreas, and ovary. To determine the representation of the elderly in clinical trials, the 1992 accrual of the National Cancer Institute (NCI)-sponsored Clinical Cooperative Group treatment trials (which included more than 8000 elderly patients) for the aforementioned sites was compared with the 1990 incidence data from the NCI's Surveillance, Epidemiology, and End Results program. Of the male patients enrolled in the trials, an average of 39% were older than 65 (47.3% lung, 79.5% prostate, 47.5% colorectal, 45.6% pancreas, and 9.6% leukemia); whereas 25.9% of all women enrolled in trials were 65 or older (43.6% lung, 17.3% breast, 46.2% colorectal, 59.6% pancreas, and 35.4% ovary). With respect to incidence, older patients generally are underrepresented in cancer treatment trials. With the exception of the data on prostate cancer, each of the comparisons using the Z statistic gave probability values of less than 0.01. The most significant discrepancies between incidence and participation in cancer treatment protocols were noted for leukemia in males and breast cancer in females. Possible explanations for these findings include (1) a research focus on aggressive therapy, which may be unacceptably toxic to the elderly; (2) presence of comorbidity in the elderly; (3) fewer trials available specifically aimed at older patients; (4) limited expectations for long term benefits on the part of physicians, relatives, and the patients themselves; and (5) a lack of financial, logistic, and social support for the participation of elderly patients in clinical trials. Recognizing this situation, NCI recently sponsored a number of trials that specifically target the elderly. This paper describes the status of all major Phase II and III clinical trials that recently were closed, still are active, or now are in review that address the clinical care of this important segment of the U.S. population. C1 EMMES CORP,POTOMAC,MD. RP TRIMBLE, EL (reprint author), NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,6130 EXECUT BLVD,SUITE 741,ROCKVILLE,MD 20852, USA. NR 7 TC 242 Z9 242 U1 1 U2 7 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 OCT 1 PY 1994 VL 74 IS 7 SU S BP 2208 EP 2214 DI 10.1002/1097-0142(19941001)74:7+<2208::AID-CNCR2820741737>3.0.CO;2-# PG 7 WC Oncology SC Oncology GA PJ094 UT WOS:A1994PJ09400036 PM 8087794 ER PT J AU HSING, AW DEVESA, SS AF HSING, AW DEVESA, SS TI PROSTATE-CANCER MORTALITY IN THE UNITED-STATES BY COHORT YEAR OF BIRTH, 1865-1940 SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article AB Prostate cancer is the second leading cause of cancer death among United States men, with rates among blacks twice those among whites. Over time, mortality has increased among nonwhites but has changed little among whites. Earlier reports have predicted that the rise among nonwhites would diminish because it appeared that those born in the late 1800s were at highest risk. Eased on 1950-1989 United States mortality data and populations at risk estimated using census data, we assessed prostate cancer mortality trends over time in white, nonwhite, and black men. From 1950-1954 to 1985-1989, age-adjusted prostate cancer mortality rates increased slightly for whites (9%) but substantially for nonwhites (67%). Among whites, rates increased over time in men over age 80 years but remained constant for younger men. Among nonwhites, rates increased steeply in those above age 74 years and slightly in the age group 65-74 years but declined in those under age 65 years, with the rate of decrease much more rapid in those under 55. The predicted reduction in risk among nonwhite men born since 1900, reported in an earlier study based on the mortality pattern through 1970, has not occurred because rates continued to increase among older nonwhites. In summary, prostate cancer mortality rates are rising among older men and decreasing in nonwhite young men. While improved detection of the cancer may partly account for the trend, analytical studies are needed to investigate the reasons for the increase in prostate cancer mortality in older men, the decrease in nonwhite young men, and the increasing excess risk among blacks. RP HSING, AW (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EPN 415,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 15 TC 11 Z9 11 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT-NOV PY 1994 VL 3 IS 7 BP 527 EP 530 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA PM725 UT WOS:A1994PM72500001 PM 7827581 ER PT J AU SWANSON, CA POTISCHMAN, N BARRETT, RJ BERMAN, ML MORTEL, R TWIGGS, LB WILBANKS, GD HOOVER, RN BRINTON, LA AF SWANSON, CA POTISCHMAN, N BARRETT, RJ BERMAN, ML MORTEL, R TWIGGS, LB WILBANKS, GD HOOVER, RN BRINTON, LA TI ENDOMETRIAL CANCER RISK IN RELATION TO SERUM-LIPIDS AND LIPOPROTEIN LEVELS SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CHOLESTEROL; DIET; HYPOCHOLESTEROLEMIA; CONSUMPTION; MORTALITY; NUTRITION; PLASMA; WOMEN; MEN; FAT AB Blood lipids are useful biochemical indicators for assessing the risk of a number of chronic diseases, particularly those associated with obesity. In a multicenter case-control study that included 256 cases and 185 controls less than 75 years old, we studied the risk of endometrial cancer in relation to serum cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and triglycerides. Contrary to expectation, blood lipids were, in general, lower among cases compared with controls. The effects of low blood lipids, specifically cholesterol and low density lipoprotein cholesterol, were limited to older women (greater than or equal to 55 years). Risk of the disease in this subgroup of 177 cases and 110 controls was increased 3-4-fold among those with the lowest cholesterol or low density lipoprotein cholesterol values. For example, after adjustment for age, education, smoking status, obesity, and body fat distribution, the relative risks of endometrial cancer across decreasing quartiles of serum cholesterol were 1.0, 2.5, 2.4, and 4.2 (P for trend < 0.01). We examined blood lipid levels by disease stage. The low lipid values of older cases did not appear to be a consequence of the disease. While we cannot rule out the possibility that hypocholesterolemia is a predisposing factor for endometrial cancer, there is no obvious biological explanation for the inverse association. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT OBSTET & GYNECOL,WINSTON SALEM,NC 27103. UNIV CALIF IRVINE,MED CTR,DEPT OBSTET & GYNECOL,IRVINE,CA 92668. PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT OBSTET & GYNECOL,HERSHEY,PA 17033. UNIV MINNESOTA,SCH MED,DEPT OBSTET & GYNECOL,MINNEAPOLIS,MN 55455. RUSH MED COLL,DEPT OBSTET & GYNECOL,CHICAGO,IL 60612. RP SWANSON, CA (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EPN SUITE 430,6130 EXECUT BLVD MSC 7366,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 42 TC 19 Z9 19 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 OCT-NOV PY 1994 VL 3 IS 7 BP 575 EP 581 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA PM725 UT WOS:A1994PM72500008 PM 7827588 ER PT J AU UEMURA, Y TOKUNAGA, M ARIKAWA, J YAMAMOTO, N HAMASAKI, Y TANAKA, S SATO, E LAND, CE AF UEMURA, Y TOKUNAGA, M ARIKAWA, J YAMAMOTO, N HAMASAKI, Y TANAKA, S SATO, E LAND, CE TI A UNIQUE MORPHOLOGY OF EPSTEIN-BARR VIRUS-RELATED EARLY GASTRIC-CARCINOMA SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article AB Epstein-Barr virus (EBV) involvement in gastric cancer is demonstrated by uniform presence of viral RNA in carcinoma cells as detected by EBV-encoded small RNA in situ hybridization, monoclonal proliferation of EBV-infected carcinoma cells, and elevated antibodies. Our review of selected early gastric cancers found that 46 of 49 EBV-positive lesions (94%) but only four of 97 EBV-negative lesions (4%) conformed to a unique morphology, in which carcinoma cells formed lace patterns of branching and/or anastomosing structures with lymphocytic infiltration in and around the carcinoma nests in the mucosa. We conclude that EBV-related gastric carcinoma has a distinct and characteristic morphology in the early stage of development, and this lace pattern is a biomarker of EBV involvement in early gastric cancer. C1 KAGOSHIMA CITY HOSP,DEPT PATHOL,KAGOSHIMA 892,JAPAN. KAGOSHIMA CITY MED ASSOC HOSP,DEPT PATHOL,KAGOSHIMA 892,JAPAN. KAGOSHIMA UNIV,FAC MED,DEPT PATHOL 2,KAGOSHIMA 890,JAPAN. NCI,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892. NR 8 TC 39 Z9 40 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT-NOV PY 1994 VL 3 IS 7 BP 607 EP 611 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA PM725 UT WOS:A1994PM72500012 PM 7827592 ER PT J AU WHANGPENG, J KNUTSEN, T JAFFE, E RAFFELD, M ZHAO, WP DUFFEY, P LONGO, DL AF WHANGPENG, J KNUTSEN, T JAFFE, E RAFFELD, M ZHAO, WP DUFFEY, P LONGO, DL TI CYTOGENETIC STUDY OF 2 CASES WITH LYMPHOMA OF MUCOSA-ASSOCIATED LYMPHOID-TISSUE SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID B-CELL LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; MYOEPITHELIAL SIALADENITIS; MALIGNANT-LYMPHOMAS; TRANSLOCATION; T(14-18); DISEASE; MALT AB Cytogenetic studies have been reported in fewer than 20 patients with lymphoma of mucosa associated lymphoid tissue (MALT). Two patients with this disease at the Clinical Center, National Institutes of Health had numerical and structural chromosome abnormalities, including +12 in both cases. The clonal karyotypes observed were 48-49,XX,t(2;8)(q33;p23),+3,-10,del(10)(q23),+12,+18 [cp] and 47,X,-X,i(6p),+7,+inv(12)(p13q13). Review of cytogenetic studies from published data showed that all cases of MALT lymphoma reported to date also have both numerical and structural chromosome abnormalities, the most frequent being numerical involvement of chromosomes 3, 7, and 12. Identification of a clonal abnormality can help establish the diagnosis when differential diagnosis includes atypical hyperplasia. Although trisomy 12 has been associated with a poor prognosis in B-cell chronic lymphocytic lymphoma (B-CLL), both these patients with MALT lymphoma have had long survival: 8 and 11 years, respectively. C1 NCI,MED BRANCH,BETHESDA,MD 20892. NCI,DEPT PATHOL,BETHESDA,MD 20892. NCI,BIOL RESPONSE MODIFIERS PROGRAM,BETHESDA,MD 20892. NR 28 TC 32 Z9 32 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD OCT 1 PY 1994 VL 77 IS 1 BP 74 EP 80 DI 10.1016/0165-4608(94)90153-8 PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA PP589 UT WOS:A1994PP58900013 PM 7923088 ER PT J AU CANMAN, CE WOLFF, AC CHEN, CY FORNACE, AJ KASTAN, MB AF CANMAN, CE WOLFF, AC CHEN, CY FORNACE, AJ KASTAN, MB TI THE P53-DEPENDENT G(1) CELL-CYCLE CHECKPOINT PATHWAY AND ATAXIA-TELANGIECTASIA SO CANCER RESEARCH LA English DT Note ID FLOW CYTOMETRIC ANALYSIS; IONIZING-RADIATION; P53 PROTEIN; DNA-DAMAGE; INDUCTION; IRRADIATION; PERTURBATIONS; SENSITIVITY; PROGRESSION; INHIBITION AB The p53 protein is a critical participant in a signal transduction pathway which mediates a G, cell cycle arrest and apoptotic cell death in mammalian cells after ionizing irradiation. Cells from patients with the cancer-prone, radiation-sensitive disorder, ataxia-telangiectasia (AT), exhibit suboptimal (delayed and/or defective) induction of p53 protein after ionizing radiation with some dependence on dose. Other protein products which participate in this signal transduction pathway, including p21(WAF1/CIP1), Gadd45, and Mdm2, are also suboptimally induced in AT cells after ionizing radiation. Induction of p53 is also abnormal in AT cells following treatment with methylmethanesulfonate and bleomycin but appears relatively normal following treatment with W-C irradiation or the topoisomerase inhibitors, etoposide and camptothecin. These results demonstrate a specific defect in this p53-dependent signal transduction pathway in AT cells. Potential models for this observed specificity of the AT defect as measured by p53 induction include problems with responses to: (a) single-strand, but not double-strand, DNA breaks; or (b) chemically, but not enzymatically, generated DNA ends. C1 JOHNS HOPKINS UNIV HOSP,JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD 21287. NCI,DIV CANC THERAPEUT,BETHESDA,MD 20892. RI Fornace, Albert/A-7407-2008; OI Fornace, Albert/0000-0001-9695-085X; Wolff, Antonio/0000-0003-3734-1063 FU NCI NIH HHS [T32CA60441]; NIEHS NIH HHS [ES05777] NR 34 TC 229 Z9 230 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1994 VL 54 IS 19 BP 5054 EP 5058 PG 5 WC Oncology SC Oncology GA PH774 UT WOS:A1994PH77400007 PM 7923116 ER PT J AU SUNG, C BLANEY, SM COLE, DE BALIS, FM DEDRICK, RL AF SUNG, C BLANEY, SM COLE, DE BALIS, FM DEDRICK, RL TI A PHARMACOKINETIC MODEL OF TOPOTECAN CLEARANCE FROM PLASMA AND CEREBROSPINAL-FLUID SO CANCER RESEARCH LA English DT Article ID TOPOISOMERASE-I INHIBITOR; PHASE-I; CONTINUOUS INFUSION; CAMPTOTHECIN; REPLICATION AB We present a physiological pharmacokinetic model that describes the plasma and cerebrospinal fluid (CSF) concentrations of topotecan [(S)-9-dimethylaminomethyl-10-hydroxycamptothecin hydrochloride, SKandF 104863-A, NSC 609699] following i.v. and intraventricular administrations in monkeys. The model consists of three physical spaces: the CSF, the plasma, and a body compartment. The model incorporates such processes as reversible conversion of topotecan lactone to an inactive hydroxy acid form, microvascular exchange between CSF and plasma, bulk CSF flow, exchange between plasma and body compartments, and elimination of drug from the plasma compartment. Several parameters in the model mere obtained from published literature on the physiology of the monkey. The model mas then fit to the plasma and CSF data to deduce the other parameters. Calculated clearances of topotecan lactone and total drug from the CSF after intraventricular injection mere 3.9 and 2.2 ml/h, respectively. Clearances of topotecan lactone and total drug from the plasma following a 10-min infusion were 26.3 liters/h/m(2) and 17.8 liters/h/m(2), respectively. The calculated ratios of the area under the concentration curve in the CSP following i.v. infusion to the area under the concentration curve in plasma mere 0.11 and 0.19 for topotecan and total drug, respectively, indicating significant CSF penetration. The volume of distribution was 0.77 liters/kg, which represents distribution in a volume approximating total body mater. The forward and reverse rate constants for the lactone-to-hydroxy acid conversion mere 1.0 and 0.29 h(-1), respectively. Comparison of the clearances (normalized to body surface area) with values reported for mice and humans shows reasonable similarity across species. This pharmacokinetic model may help guide future development and refinement of clinical protocols, especially in the treatment of diseases of the central nervous system. C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. WALTER REED ARMY MED CTR,DEPT PEDIAT,WASHINGTON,DC. RP SUNG, C (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 13,ROOM 3N17,BETHESDA,MD 20892, USA. NR 17 TC 45 Z9 45 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 OCT 1 PY 1994 VL 54 IS 19 BP 5118 EP 5122 PG 5 WC Oncology SC Oncology GA PH774 UT WOS:A1994PH77400019 PM 7923128 ER PT J AU DOLAN, ME CHAE, MY PEGG, AE MULLEN, JH FRIEDMAN, HS MOSCHEL, RC AF DOLAN, ME CHAE, MY PEGG, AE MULLEN, JH FRIEDMAN, HS MOSCHEL, RC TI METABOLISM OF O-6-BENZYLGUANINE, AN INACTIVATOR OF O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE SO CANCER RESEARCH LA English DT Article ID TUMOR XENOGRAFTS; ALKYLATING-AGENTS; CROSS-LINKING; CELL-LINES; SENSITIVITY; 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA; DNA; O6-BENZYLGUANINE; CHLOROETHYLNITROSOUREA; DEPLETION AB O-6-Benzylguanine effectively inactivates the DNA repair protein, O(-)alkylguanine-DNA alkyltransferase, leading to an increase in the therapeutic index of 1,3-bis(2-chloroethyl)-1-nitrosourea in nude mouse xenograft studies. To investigate the fate of this inactivator in mammalian systems, we examined it biodistribution and metabolism following i.p. administration of 8-[H-3]-O-6-benzylguanine to male Sprague-Dawley rats and BALB/c mice. Following administration to rats, there were significantly higher levels of radioactivity in liver than in lung, spleen, kidney, small intestine, and esophagus for us to 24 h. Major urinary metabolites were identified as O-6-benzyl-7,8-dihydro-8-oxoguanine, N-2-acetyl-O-6-benzylguanine, and N-2-acetyl-O-6-benzyl-7,8-dihydro-8-oxoguanine. Debenzylated metabolites included guanine, 7,8-dihydro-8-oxoguanine, and N-2- acetylguanine. In contrast to rat metabolism, acetylated derivatives were not found in mouse urine. However, O-6-benzyl-7,8-dihydro-8-oxoguanine was a major metabolite in the mouse. O-6-Benzyl-7,8-dihydro-8-oxoguanine was a very effective O-6-alkylguanine-DNA alkyl-transferase inactivator and exhibited a 50% effective dose in HT29 cell extracts of 0.3. mu M compared to 0.2. mu M for O-6-benzylguanine. The O-6-alkylguanine-DNA alkyltransferase depleting activity of N-2-acetyl-O-6-benzylguanine and N-2-acetyl-O-6-benzyl-7,8-dihydro-8-oxoganine were, respectively, 120- and 325-fold lower than O-6-benzylguanine in HT29 cell-free extracts. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. PENN STATE UNIV,COLL MED,MILTON S HERSHEY MED CTR,DEPT CELLULAR & MOLEC PHYSIOL,HERSHEY,PA 17033. PENN STATE UNIV,COLL MED,MILTON S HERSHEY MED CTR,DEPT PHARMACOL,HERSHEY,PA 17033. DUKE UNIV,MED CTR,DEPT PEDIAT,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT PATHOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,PREUSS LAB BRAIN TUMOR RES,DURHAM,NC 27710. RP DOLAN, ME (reprint author), UNIV CHICAGO,DIV HEMATOL ONCOL,CHICAGO,IL 60637, USA. FU NCI NIH HHS [CA57725, CA47228, CA-18137] NR 28 TC 59 Z9 61 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1994 VL 54 IS 19 BP 5123 EP 5130 PG 8 WC Oncology SC Oncology GA PH774 UT WOS:A1994PH77400020 PM 7923129 ER PT J AU KIHARA, A PASTAN, I AF KIHARA, A PASTAN, I TI SMALL CHIMERIC TOXINS CONTAINING ONLY TRANSFORMING GROWTH-FACTOR-ALPHA AND DOMAIN-III OF PSEUDOMONAS EXOTOXIN WITH GOOD ANTITUMOR-ACTIVITY IN MICE SO CANCER RESEARCH LA English DT Article ID FUSION PROTEIN; RECOMBINANT FORM; FACTOR RECEPTORS; IMMUNOTOXINS; BLADDER; CANCER; CELLS AB Chimeric toxins composed of transforming growth factor alpha (TGF alpha) fused to mutant forms of Pseudomonas exotoxin (PE) bind to the epidermal growth factor receptor and kill cells bearing epidermal growth factor receptors. Initially, the binding domain (Is; amino acids 1-252) of PE was deleted and replaced with TGF alpha to make TGF alpha-PE40 in which TGF alpha is fused to domains II, Ib, and III of PE (amino acids 253-613). That drug is currently undergoing clinical study for the intravesical therapy of bladder cancer. To generate smaller molecules that mould have increased tumor penetration, several deletion mutants were constructed. In one of these, TGF alpha was inserted near the carboxyl terminus of PE, and residues in domains II and Ib of PE (amino acids 253-279 and 365-380) were deleted so that the chimeric toxin did not need to be cleaved by an intracellular protease to be activated (Theuer ct al., J. Biol. Chem., 267: 16872-16877, 1992). We have now constructed chimeric toxins which contain only domain III, yet still exhibit high cytotoxic activity on epidermal growth factor receptor-containing cells and produce substantial tumor regressions in mice bearing a human xenograft. The high cytotoxic activity of these severely truncated toxins provides nem insights on the proposed functions of domains II and III of PE. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 31 TC 13 Z9 13 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1994 VL 54 IS 19 BP 5154 EP 5159 PG 6 WC Oncology SC Oncology GA PH774 UT WOS:A1994PH77400025 PM 7923133 ER PT J AU SLOANE, BF HERMAN, CJ PADARATHSINGH, M AF SLOANE, BF HERMAN, CJ PADARATHSINGH, M TI MOLECULAR MECHANISMS OF PROGRESSION AND METASTASIS OF HUMAN TUMORS - A PATHOLOGY-B STUDY SECTION WORKSHOP SO CANCER RESEARCH LA English DT Editorial Material C1 NIH,DIV RES GRANTS,PATHOL B STUDY SECT,BETHESDA,MD 20892. WAYNE STATE UNIV,DEPT PHARMACOL,DETROIT,MI 48201. GRADY MEM HOSP,DEPT PATHOL ANAT,ATLANTA,GA 30335. RI Sloane, Bonnie/A-1050-2009 NR 0 TC 2 Z9 2 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 OCT 1 PY 1994 VL 54 IS 19 BP 5241 EP 5245 PG 5 WC Oncology SC Oncology GA PH774 UT WOS:A1994PH77400039 PM 7923147 ER PT J AU TAKESHIMA, Y INAI, K BENNETT, WP METCALF, RA WELSH, JA YONEHARA, S HAYASHI, Y FUJIHARA, M YAMAKIDO, M AKIYAMA, M TOKUOKA, S LAND, CE HARRIS, CC AF TAKESHIMA, Y INAI, K BENNETT, WP METCALF, RA WELSH, JA YONEHARA, S HAYASHI, Y FUJIHARA, M YAMAKIDO, M AKIYAMA, M TOKUOKA, S LAND, CE HARRIS, CC TI P53 MUTATIONS IN LUNG CANCERS FROM JAPANESE MUSTARD GAS WORKERS SO CARCINOGENESIS LA English DT Article ID TUMOR-SUPPRESSOR GENE; CELL CARCINOMAS; HEPATOCELLULAR CARCINOMAS; ENZYMATIC AMPLIFICATION; ESOPHAGEAL CANCER; DNA-POLYMERASE; SULFUR MUSTARD; LESIONS; REPAIR; ABERRATIONS AB Mustard gas (MG) is a mutagenic and carcinogenic alkylating agent, and is a known risk factor for occupational lung cancer. Our hypothesis is that lung cancers from MG workers contain mutations (G:C to A:T transitions)as the result of MG-produced DNA promutagenic adducts in the p53 tumor suppressor gene, We analyzed 12 primary lung cancers from Japanese MG factory workers and 12 lung cancers from non-exposed individuals. Genomic DNA was isolated from archival paraffin-embedded tissues. Exons 5-8 were amplified by polymerase chain reaction using p53-specific primers, and sequenced by dideoxy. termination methods. Six out of 12 lung cancers from MG workers contained a total of eight somatic point mutations: two cases had double G:C to A:T transitions; one had a G:C to T:A transversion; one case had an A:T to G:C transition; and two cases had single base deletions. Four of the six mutated purines occurred on the non-transcribed, DNA-coding strand. Out of 12 unexposed cases, there were six single base mutations in six cancers, and no double mutations. The p53 mutational frequency in the MG-exposed cases is similar to the non-exposed controls and the usual smoking-related lung cancers reported previously. However, the distinctive double mutations (G:C to A:T transition) observed in two cases are unusual and may be related to MG exposure. C1 NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892. HIROSHIMA UNIV,SCH MED,DEPT PATHOL,HIROSHIMA 734,JAPAN. HIROSHIMA UNIV,SCH MED,DEPT INTERNAL MED,HIROSHIMA 734,JAPAN. RADIAT EFFECTS RES FDN,DEPT EPIDEMIOL PATHOL,HIROSHIMA 732,JAPAN. RADIAT EFFECTS RES FDN,DEPT RADIOBIOL,HIROSHIMA 732,JAPAN. HIROSHIMA CITY ASA HOSP,DEPT PATHOL,HIROSHIMA 73102,JAPAN. HIROSHIMA RED CROSS,DEPT PATHOL,HIROSHIMA 730,JAPAN. ATOM BOMB SURVIVORS HOSP,HIROSHIMA 730,JAPAN. FU PHS HHS [NEC-4893-8-001] NR 54 TC 48 Z9 48 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 1994 VL 15 IS 10 BP 2075 EP 2079 DI 10.1093/carcin/15.10.2075 PG 5 WC Oncology SC Oncology GA PM733 UT WOS:A1994PM73300001 PM 7955036 ER PT J AU YAGER, JD ZURLO, J SEWALL, CH LUCIER, GW HE, HC AF YAGER, JD ZURLO, J SEWALL, CH LUCIER, GW HE, HC TI GROWTH-STIMULATION FOLLOWED BY GROWTH-INHIBITION IN LIVERS OF FEMALE RATS TREATED WITH ETHINYL ESTRADIOL SO CARCINOGENESIS LA English DT Article ID HEPATIC TUMOR PROMOTERS; INDUCED DNA-SYNTHESIS; CHOLINE-DEVOID DIET; FACTOR RECEPTOR; PEROXISOME PROLIFERATION; CELL-PROLIFERATION; ESTROGEN-RECEPTOR; CLOFIBRIC ACID; POSITIVE FOCI; OROTIC-ACID AB Ethinyl estradiol (EE) is a strong promoter of hepatocarcinogenesis in female rats. A common effect shared by many non-genotoxic hepatic promoters is the stimulation of hyperplastic growth. However, studies by others with several hepatic promoters have shown that following an initial, transient increase in liver growth, continued exposure causes an inhibition in basal and/or induced growth. We have shown that EE also causes an initial, transient increase in hepatocyte proliferation (Carcinogenesis, 7, 2007-20014, 1986). The objective of the investigation reported here was to determine whether chronic EE treatment also becomes inhibitory to basal and/or induced liver growth. Female Lewis rats were treated with EE at 2.5 and 5.0 mu g/rat/day using time-release tablets. Seven days prior to sacrifice, the rats were implanted with osmotic minipumps containing bromodeoxyuridine (BrdU) to allow the cumulative labeling of replicating hepatocytes, At sacrifice, liver tissue was fixed, sectioned and the percent labeled hepatocyte nuclei determined by immunohistochemistry. The results of these experiments revealed that, as expected, during the first 7 days of treatment, EE increased hepatocyte proliferation. However, after 28 and 42 days of EE treatment, the basal level of liver growth was dramatically inhibited. Thus, hepatocyte nuclear labeling indices, compared to controls, were reduced by 72 and 88% after 28 and 42 days of treatment respectively. An analysis of I-125-labeled EGF binding to isolated liver membranes revealed that EGF receptor levels decreased during the initial period of growth, but had returned to control levels by day 21 when replication had ceased. In another experiment, rats were treated with EE at 5.0 mu g/rat/day for 21 days; control rats received placebo time-release tablets. At the end of that time, the rats were surgically partially hepatectomized and the level of subsequent regenerative DNA synthesis was determined using [H-3]thymidine administered 2 h prior to sacrifice 24, 48, 72 and 96 h later. The results showed that EE caused an inhibition of regenerative growth. While at each time point the level of DNA synthesis in EE-treated rats was not significantly less than in corresponding controls, statistical analysis indicated that overall, EE caused a significant reduction in liver growth. The results of these studies demonstrate that chronic EE treatment leads to the appearance of a mitosuppressed state in the liver which is characterized by reduced cell turnover and decreased growth responsiveness. These results indicate that ethinyl estradiol should be added to the list of promoters of hepatocarcinogenesis which, upon continued treatment, subsequently cause mitosuppressive effects, Furthermore, together with the findings of others with other hepatic promoters, our results illustrate that initial proliferative effects may have little bearing on promoting potential. It now becomes important to determine whether promotion by EE actually involves differential mitoinhibitory effects in non-initiated versus initiated hepatocytes. C1 NIEHS, RES TRIANGLE PK, NC 27709 USA. RP YAGER, JD (reprint author), JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, DEPT ENVIRONM HLTH SCI, DIV TOXICOL SCI, 615 N WOLFE ST, BALTIMORE, MD 21205 USA. FU NCI NIH HHS [CA 36701]; NIEHS NIH HHS [ES 03819] NR 45 TC 46 Z9 46 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 1994 VL 15 IS 10 BP 2117 EP 2123 DI 10.1093/carcin/15.10.2117 PG 7 WC Oncology SC Oncology GA PM733 UT WOS:A1994PM73300008 PM 7955042 ER PT J AU WINK, DA LAVAL, J AF WINK, DA LAVAL, J TI THE FPG PROTEIN, A DNA-REPAIR ENZYME, IS INHIBITED BY THE BIOMEDIATOR NITRIC-OXIDE IN-VITRO AND IN-VIVO SO CARCINOGENESIS LA English DT Article ID APURINIC APYRIMIDINIC SITES; WOODCHUCK HEPATITIS-VIRUS; ESCHERICHIA-COLI; ALPHA-1-PROTEINASE INHIBITOR; NITROGEN-DIOXIDE; MARMOTA-MONAX; GLYCOSYLASE; COMPLEXES; ABILITY; NITRATE AB Nitric oxide has been shown to be a mediator molecule in the regulation of many physiological functions. However, this small diatomic molecule in the presence of O-2 generates reactive intermediates which modify DNA bases and inactive enzymes at high concentrations (100 mu M). We report that NO generated by 1,1-diethyl-2-hydroxy-2-nitrosohydrazine (DEA/NO, Et(2)NN(O)NO-Na+), a compound known to release NO in a predictable manner, caused irreversible damage at physiological concentrations to the zinc finger-containing DNA repair enzyme formamidopyrimidine-DNA glycolyase (Fpg protein). The inhibition of the enzyme activity was DEA/NO dose and time dependent with IC(50)s with respect to total NO released from this compound of approximate to 110 and approximate to 120 mu mol/l respectively. This inhibitory effect by NO was not reversible over time in the presence of reducing agents and/or Zn2+. Nitrite and diethylamine, the nitrogenous products of the decomposition of DEA/NO, did not inhibit the enzyme. The presence of 500 mu g/ml bovine serum albumin did not protect the protein from the inhibitory effects of DEA/NO, however, the presence of 10 mM cysteine did dramatically abate the inhibition of the Fpg protein by DEA/NO. Other DNA glycosylases tested were not inhibited by exposure to these concentrations of NO. These results, together with reports of site-directed mutagenesis of this protein, suggest that the cysteine residues contained within the zinc finger motif of the Fpg protein are the primary sites of NO interaction. Our studies were then extended to intact cells. The Fpg protein activity was decreased following treatment in vivo when Escherichia coli MH321 (acr A(-)) cells were treated with DEA/NO. Furthermore, the Fapy-DNA glycosylase activity in H4 cells, a rat hepatoma line, was decreased when intact cells were incubated with DEA/NO. C1 INST GUSTAVE ROUSSY PR2, REPARAT LES RADIO & CHIM IND GRP, CNRS, URA 147, F-94805 VILLEJUIF, FRANCE. RP WINK, DA (reprint author), NCI, FREDERICK CANC RES & DEV CTR, COMPARAT CARCINOGENESIS LAB, CHEM SECT, FREDERICK, MD 21702 USA. NR 35 TC 131 Z9 132 U1 3 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 1994 VL 15 IS 10 BP 2125 EP 2129 DI 10.1093/carcin/15.10.2125 PG 5 WC Oncology SC Oncology GA PM733 UT WOS:A1994PM73300009 PM 7955043 ER EF