FN Thomson Reuters Web of Science™ VR 1.0 PT J AU GOPALSRIVASTAVA, R PIATIGORSKY, J AF GOPALSRIVASTAVA, R PIATIGORSKY, J TI THE MURINE ALPHA-B-CRYSTALLIN SMALL HEAT-SHOCK PROTEIN ENHANCER - IDENTIFICATION OF ALPHA-BE-1, ALPHA-BE-2, ALPHA-BE-3, AND MRF CONTROL ELEMENTS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MUSCLE REGULATORY FACTORS; NON-LENTICULAR TISSUES; A-CRYSTALLIN; LENS CRYSTALLINS; TRANSGENIC MICE; HA-RAS; V-MOS; EXPRESSION; GENE; ACTIVATION AB The murine alphaB-crystallin gene (a member of the small heat shock protein family) is expressed constitutively at high levels in the lens and at lower levels in many other tissues, including skeletal muscle. We have previously used the herpes simplex virus thymidine kinase promoter fused to the human growth hormone gene to identify an alphaB-crystallin enhancer at positions -427 to -259 that has high activity in muscle and low activity in lens cell lines. In the study reported here, we performed DNase I footprinting, transfection, mutagenesis, and electrophoretic mobility shift experiments using the murine C2Cl2 muscle and alphaTN4-1 lens cell lines and the rabbit N/N1003A lens cell line to identify sequences responsible for activity of this enhancer. Enhancer activity in both the muscle and lens cells was dependent on novel elements called alphaBE-1 (-407 to -397), alphaBE-2 (-360 to -327), and alphaBE-3 (-317 to -306). These elements were also weakly occupied by nuclear proteins in L929 cells, which appear to express the alphaB-crystallin gene at a very low level (detectable only by the polymerase chain reaction). A fourth element containing a consensus muscle regulatory factor-binding site called MRF (-300 to -288) was occupied and used only by the C2C12 muscle cells. Cotransfection in NIH 3T3 cells and antibody-gel shift experiments using C2C12 nuclear extracts indicated that MyoD, myogenin, or a similar member of this family can activate the alphaB-crystallin enhancer by interaction with the MRF site. Taken together, we conclude that the alphaBE-1, alphaBE-2, and alphaBE-3 elements are shared by both lens and muscle cells, but the MRF element is used only in muscle cells, providing the first example of a muscle-specific control element in a crystallin gene. C1 NEI, MOLEC & DEV BIOL LAB, BETHESDA, MD 20892 USA. NR 51 TC 47 Z9 47 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1993 VL 13 IS 11 BP 7144 EP 7152 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MC844 UT WOS:A1993MC84400052 PM 8413303 ER PT J AU FABIAN, JR DAAR, IO MORRISON, DK AF FABIAN, JR DAAR, IO MORRISON, DK TI CRITICAL TYROSINE RESIDUES REGULATE THE ENZYMATIC AND BIOLOGICAL-ACTIVITY OF RAF-1 KINASE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SERINE-THREONINE KINASE; PROTEIN-KINASE; SIGNAL TRANSDUCTION; MAP KINASE; B-RAF; CELL-LINE; V-RAF; ACTIVATION; PHOSPHORYLATION; GROWTH AB The serine/threonine kinase activity of the Raf-1 proto-oncogene product is stimulated by the activation of many tyrosine kinases, including growth factor receptors and pp60v-src. Recent studies of growth factor signal transduction pathways demonstrate that Raf-1 functions downstream of activated tyrosine kinases and p21ras and upstream of mitogen-activated protein kinase. However, coexpression of both activated tyrosine kinases and p21ras is required for maximal activation of Raf-1 in the baculovirus-Sf9 expression system. In this study, we investigated the role of tyrosine kinases and tyrosine phosphorylation in the regulation of Raf-I activity. Using the baculovirus-Sf9 expression system, we identified Tyr-340 and Tyr-341 as the major tyrosine phosphorylation sites of Raf-1 when coexpressed with activated tyrosine kinases. Introduction of a negatively charged residue that may mimic the effect of phosphorylation at these sites activated the catalytic activity of Raf-1 and generated proteins that could transform BALB/3T3 cells and induce the meiotic maturation of Xenopus oocytes. In contrast, substitution of noncharged residues that were unable to be phosphorylated produced a protein that could not be enzymatically activated by tyrosine kinases and that could block the meiotic maturation of oocytes induced by components of the receptor tyrosine kinase pathway. These findings demonstrate that mutation of the tyrosine phosphorylation sites can dramatically alter the function of Raf-1. In addition, this is the first report that a transforming Raf-1 protein can be generated by a single amino acid substitution. C1 NCI, FREDERICK CANC RES & DEV CTR, MOLEC MECHAN CARCINOGENESIS LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, LEUKOCYTE BIOL LAB, BIOL RESPONSE MODIFIERS PROGRAM, FREDERICK, MD 21702 USA. OI Daar, Ira/0000-0003-2657-526X FU NCI NIH HHS [N01-CO-74101] NR 52 TC 298 Z9 302 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1993 VL 13 IS 11 BP 7170 EP 7179 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MC844 UT WOS:A1993MC84400055 PM 7692235 ER PT J AU HADARI, YR GEIGER, B NADIV, O SABANAY, I ROBERTS, CT LEROITH, D ZICK, Y AF HADARI, YR GEIGER, B NADIV, O SABANAY, I ROBERTS, CT LEROITH, D ZICK, Y TI HEPATIC TYROSINE-PHOSPHORYLATED PROTEINS IDENTIFIED AND LOCALIZED FOLLOWING IN-VIVO INHIBITION OF PROTEIN-TYROSINE PHOSPHATASES - EFFECTS OF H2O2 AND VANADATE ADMINISTRATION INTO RAT LIVERS SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE TYROSINE PHOSPHORYLATION (RAT LIVER); PROTEIN TYROSINE KINASE; H2O2-VANADATE ID INSULIN-RECEPTOR KINASE; PHOSPHOLIPASE-C-GAMMA; SIGNAL TRANSDUCTION; PHOSPHATIDYLINOSITOL 3-KINASE; GLYCOGEN-SYNTHASE; HYDROGEN-PEROXIDE; INTACT-CELLS; ADIPOCYTES; SUBSTRATE; STIMULATION AB Injection of a combination of H2O2 and vanadate (H/V) into the portal vein of rat livers resulted in inhibition of protein tyrosine phosphatase activity and led to a dramatic enhanced in vivo protein tyrosine phosphorylation. Some of the phosphorylated proteins were identified as the beta-subunit of the insulin receptor, the insulin receptor substrate 1 (pp185), PLC-gamma (pp145), and a 100 kDa PLC-gamma-associated protein. Immunofluorescense and immune electron microscopy of frozen liver sections with anti-P-Tyr antibodies revealed that most of the tyrosine-phosphorylated proteins are localized in close proximity to the plasma membrane in intercellular adherence junctions and tight junction regions. This close in vivo association between membranal protein tyrosine kinases, their target proteins, and cytoskeletal elements could enable formation of 'signaling complexes' which may play a role in transmembrane signal transduction. By affinity chromatography over immobilized anti-P-Tyr antibodies, a large number of these tyrosine-phosphorylated proteins were partially purified. C1 WEIZMANN INST SCI,DEPT CHEM IMMUNOL,IL-76100 REHOVOT,ISRAEL. NIH,DIABET BRANCH,BETHESDA,MD 20892. OI Roberts, Charles/0000-0003-1756-5772 NR 47 TC 40 Z9 41 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD NOV PY 1993 VL 97 IS 1-2 BP 9 EP 17 DI 10.1016/0303-7207(93)90206-Y PG 9 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA MU125 UT WOS:A1993MU12500003 PM 8143908 ER PT J AU YEN, PM SUGAWARA, A FORGIONE, M SPANJAARD, RA MACCHIA, E CHENG, SY CHIN, WW AF YEN, PM SUGAWARA, A FORGIONE, M SPANJAARD, RA MACCHIA, E CHENG, SY CHIN, WW TI REGION-SPECIFIC ANTITHYROID HORMONE-RECEPTOR (TR) ANTIBODIES DETECT CHANGES IN TR STRUCTURE DUE TO LIGAND-BINDING AND DIMERIZATION SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE THYROID HORMONE RECEPTOR; ANTI-TR ANTIBODY; MONOMER; HOMODIMER; HETERODIMER; TRANSCRIPTIONAL REGULATION ID RESPONSE ELEMENTS; RETINOIC ACID; DNA-BINDING; C-ERBA; GENERALIZED RESISTANCE; ENHANCES BINDING; TRANS-ACTIVATION; RXR-BETA; PROTEIN; COMPLEXES AB There are multiple factors that potentially can induce structural changes in DNA-bound thyroid hormone receptors (TRs) including protein-protein interactions, ligand-binding to TRs, and the thyroid hormone response element (TRE) sequence. We used a battery of anti-TR antibodies that recognize the amino-terminal, hinge, or carboxy-terminal regions of TRs to study changes in the epitope regions of in vitro translated TRs in electrophoretic mobility shift assays. We found that the carboxy-terminal and hinge region antibodies recognized TR homodimers but not TR/T-3-receptor auxiliary protein or TR/retinoid X receptor heterodimers. The amino-terminal antibodies detected conformational changes due to ligand binding. In contrast, each antibody recognized TR complexes bound to TREs containing half-sites arranged in three different orientations. These results suggest that dimerization with nuclear proteins and ligand-binding, rather than the orientation of TRE half-sites. cause changes in several TR subregions. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV PISA,IST ENDOCRINOL,PISA,ITALY. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. RP YEN, PM (reprint author), BRIGHAM & WOMENS HOSP,DEPT MED,DIV GENET,20 SHATTUCK ST,BOSTON,MA 02115, USA. NR 35 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD NOV PY 1993 VL 97 IS 1-2 BP 93 EP 99 DI 10.1016/0303-7207(93)90214-5 PG 7 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA MU125 UT WOS:A1993MU12500011 PM 7511545 ER PT J AU KOLBANOVSKAYA, EY MOROZOV, NY GAVRYUSHOV, SA ILIN, VA BEINTEMA, JJ WLODAWER, A KARPEISKY, MY AF KOLBANOVSKAYA, EY MOROZOV, NY GAVRYUSHOV, SA ILIN, VA BEINTEMA, JJ WLODAWER, A KARPEISKY, MY TI STRUCTURAL-FUNCTIONAL ANALYSIS OF RIBONUCLEASE-A AND RELATED PROTEINS SO MOLECULAR BIOLOGY LA English DT Article DE RNASE-A; PANCREATIC RNASES; ANGIOGENIN; HOMOLOGOUS PROTEIN FAMILIES; HYDROPHOBIC NUCLEI ID AMINO-ACID-SEQUENCE; TURTLE PANCREATIC RIBONUCLEASE; INTRAMOLECULAR INTERACTIONS; SECONDARY STRUCTURE; PACKING; RNASE; ANGIOGENIN; HOMOLOGY; ACCESSIBILITY; PREDICTIONS AB A detailed analysis of noncovalent interactions in RNase A is carried out with the use of contact maps generated on the basis of X-ray structural investigations. Three hydrophobic nuclei and five microclusters could be identified in the RNase A molecule and their quantitative characteristics were presented. Contacts between amino acid residues of the active center and hydrophobic nuclei were established. The distribution of charged groups over the surface of the RNase molecule was determined. The results obtained are discussed in the context of a family of mammalian pancreatic RNases and a superfamily of RNase A which includes the proteins possessing RNase and another biological activity. A mechanism was suggested by which the changes observed upon alignment of amino acid sequences in the proteins of the families can affect the spatial structure and mutual orientation of different sites of RNase A and, thereby, the biological activity of the proteins of the families. C1 BIOCHEM LAB,9747 AG GRONINGEN,NETHERLANDS. AV SHUBNIKOV INST CRYSTALLOG,MOSCOW 117333,RUSSIA. NCI,FREDERICK CANC RES & DEV CTR,MACROMOLEC STRUCT LAB,FREDERICK,MD 21702. RP KOLBANOVSKAYA, EY (reprint author), VA ENGELHARDT INST MOLEC BIOL,MOSCOW 117984,RUSSIA. NR 53 TC 7 Z9 7 U1 0 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA CONSULTANTS BUREAU 233 SPRING ST, NEW YORK, NY 10013 SN 0026-8933 J9 MOL BIOL+ JI Mol. Biol. PD NOV-DEC PY 1993 VL 27 IS 6 BP 821 EP 836 PN 2 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PC041 UT WOS:A1993PC04100001 ER PT J AU DING, DM TOTH, M ZHOU, YZ PARKS, C HOFFMAN, BJ SHENK, T AF DING, DM TOTH, M ZHOU, YZ PARKS, C HOFFMAN, BJ SHENK, T TI GLIAL CELL-SPECIFIC EXPRESSION OF THE SEROTONIN-2 RECEPTOR GENE - SELECTIVE REACTIVATION OF A REPRESSED PROMOTER SO MOLECULAR BRAIN RESEARCH LA English DT Article DE SEROTONIN 5-HT(2) RECEPTOR; GENE REGULATION; PROMOTER; REPRESSION; REACTIVATION; GLIAL CELL ID DNA-BINDING FACTOR; TRANSCRIPTION INVITRO; MAMMALIAN-CELLS; MESSENGER-RNA; REGULATORY ELEMENTS; SILENCER ELEMENT; 5-HT2 RECEPTOR; LESS PROMOTER; SCG10 GENE; ENHANCER AB The 5' flanking region of the 5-HT2 receptor gene has been cloned, sequenced and its transcriptional regulatory functions analyzed. The promoter lacks an identifiable TATA motif, and utilizes at least 11 clustered start sites. Promoter function was analyzed by transient assays in rat C6 glioma cells, which were shown to express the endogenous 5-HT2 receptor gene, as well as in rat CREF and human HeLa cells which do not express the endogenous gene. The basal promoter functioned equally well in all three cell lines; and a repression domain, located upstream of the basal promoter, inhibited activity of the promoter in all three cell lines. A far upstream cell specific activator domain restored promoter activity in C6 glioma cells, but did not reactivate the silenced promoter in CREF or HeLa cells. The upstream activator domain, repressor domain and basal promoter functioned in concert to achieve cell type specific expression. The activator domain did not direct C6 glioma cell specific expression in the absence of the repressor domain or in constructs carrying a heterologous basal promoter. These results indicate that glial cell expression of the 5-HT2 receptor gene is achieved through a cell type specific reactivation of a repressed promoter. C1 PRINCETON UNIV,HOWARD HUGHES MED INST,DEPT MOLEC BIOL,PRINCETON,NJ 08544. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NR 43 TC 40 Z9 40 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 1993 VL 20 IS 3 BP 181 EP 191 DI 10.1016/0169-328X(93)90040-V PG 11 WC Neurosciences SC Neurosciences & Neurology GA MF871 UT WOS:A1993MF87100001 PM 8302156 ER PT J AU STRAUSS, KI JACOBOWITZ, DM AF STRAUSS, KI JACOBOWITZ, DM TI QUANTITATIVE MEASUREMENT OF CALRETININ AND BETA-ACTIN MESSENGER RNAIN RAT-BRAIN MICROPUNCHES WITHOUT PRIOR ISOLATION OF RNA SO MOLECULAR BRAIN RESEARCH LA English DT Article DE MESSENGER RNA QUANTITATION; RIBONUCLEASE PROTECTION ASSAY; CALRETININ; BETA-ACTIN; RAT BRAIN; IN-SITU HYBRIDIZATION HISTOCHEMISTRY ID CALCIUM-BINDING PROTEIN; IMMUNOHISTOCHEMICAL LOCALIZATION; PROTECTION ASSAY; GENE; EXPRESSION; NEURONS; HYBRIDIZATION; FOREBRAIN; SEQUENCE AB A microdissection technique for quantitation of neurochemicals in discrete brain nuclei has been applied to quantitative measurement of mRNA. The method permits quantitation of low abundance mRNA from submilligram amounts of tissue (10-500 mug protein). Discrete nuclei and other regions of the brain are solubilized in concentrated guanidine thiocyanate solution, mRNA is directly hybridized with riboprobes, and detected with a ribonuclease protection assay. This method eliminates the necessity for RNA isolation from solid tissue. No assumptions regarding RNA recovery are necessary since tissue specimens are solubilized, hybridized and treated with ribonuclease in a single tube. We have determined the mRNA levels of calretinin, a predominantly neuron-specific calcium binding protein in microdissected nuclei and other regions of rat brain. For interassay comparison, measurement of sample protein and beta-actin mRNA permits normalization and quantitation in terms of these internal controls. The quantity of calretinin mRNA ranged from 281 +/- 35 fg/mug protein in the thalamic paraventricular nucleus to 2.3 +/- 0.5 fg/mug protein for the cerebral cortex. The calretinin/beta-actin ratios ranged from 79.9 +/- 9.3% to 1.3 +/- 0.1%, respectively. The combination of microdissection techniques with a lysate RNase protection assay: (1) establishes this technique as quantitative for detection of high and low abundance mRNAs from microdissected brain specimens; (2) bypasses the inefficiencies and uncertainties associated with isolating RNA; and (3) enables large numbers of determinations from discrete brain nuclei to be analyzed in 2 to 3 days. RP STRAUSS, KI (reprint author), NIMH,CLIN SCI LAB,BLDG 10,ROOM 3D-48,BETHESDA,MD 20892, USA. NR 26 TC 30 Z9 30 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 1993 VL 20 IS 3 BP 229 EP 239 DI 10.1016/0169-328X(93)90045-Q PG 11 WC Neurosciences SC Neurosciences & Neurology GA MF871 UT WOS:A1993MF87100006 PM 8302161 ER PT J AU NORDSTROM, K AUSTIN, SJ AF NORDSTROM, K AUSTIN, SJ TI CELL-CYCLE-SPECIFIC INITIATION OF REPLICATION SO MOLECULAR MICROBIOLOGY LA English DT Review ID ESCHERICHIA-COLI-CELLS; F-PLASMID REPLICATION; CHROMOSOMAL REPLICATION; DNA-REPLICATION; FLOW-CYTOMETRY; PROTEIN; K-12; RNA AB The following characteristics are relevant when replication of chromosomes and plasmids is discussed in relation to the cell cycle: the timing or replication, the selection of molecules for replication, and the coordination of multiple initiation events within a single cell cycle. Several fundamentally different methods have been used to study these processes: Meselson-Stahl density-shift experiments, experiments with the so-called 'baby machine', sorting of cells according to size, and flow cytometry. The evidence for precise timing and co-ordination of chromosome replication in Escherichia coli is overwhelming. Similarly, the high-copy-number plasmid ColE1 and the low-copy-number plasmids R1/R100 without any doubt replicate randomly throughout the cell cycle. Data about the low-copy-number plasmids F and P1 are conflicting. This calls for new types of experiments and for a better understanding of how these plasmids control their replication and partitioning. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHROMOSOME BIOL LAB,FREDERICK,MD 21702. RP NORDSTROM, K (reprint author), UNIV UPPSALA,CTR BIOMED,DEPT MICROBIOL,S-75123 UPPSALA,SWEDEN. FU NCI NIH HHS [N01-CO-74101] NR 43 TC 14 Z9 14 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD NOV PY 1993 VL 10 IS 3 BP 457 EP 463 DI 10.1111/j.1365-2958.1993.tb00918.x PG 7 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA MF565 UT WOS:A1993MF56500002 PM 7968524 ER PT J AU FUKAMAUCHI, F SAUNDERS, PA HOUGH, C CHUANG, DM AF FUKAMAUCHI, F SAUNDERS, PA HOUGH, C CHUANG, DM TI AGONIST-INDUCED DOWN-REGULATION AND ANTAGONIST-INDUCED UP-REGULATION OF M(2)-MUSCARINE AND M(3)-MUSCARINIC ACETYLCHOLINE-RECEPTOR MESSENGER-RNA AND PROTEIN IN CULTURED CEREBELLAR GRANULE CELLS SO MOLECULAR PHARMACOLOGY LA English DT Article ID MUSCARINIC CHOLINERGIC RECEPTORS; INOSITOL-PHOSPHOLIPID-METABOLISM; PHOSPHOINOSITIDE TURNOVER; DIFFERENTIAL REGULATION; ADENYLATE-CYCLASE; NG108-15 CELLS; ACID RELEASE; RAT-BRAIN; C-FOS; EXPRESSION AB Cerebellar granule cells express m2- and m3-muscarinic acetylcholine receptors (mAChRs) and their corresponding mRNA with M3-mAChR being the predominant receptor subtype. After stimulation with the mAChR agonist, carbachol, m2- and m3-mAChR mRNA levels were decreased in a time- and concentration-dependent manner with the maximal down-regulation at 2 and 8 hr, respectively. Immunoprecipitation studies revealed that amounts Of M2- and M3-mAChR protein also decreased at 8 and 24 hr, respectively. The carbachol-induced down-regulation of M3-mAChR mRNA was associated with a decrease in the transcription rate, but a substantial enhancement of the mRNA stability. Upon removal of carbachol after treatment for 8 hr, the levels Of M3-mAChR mRNA and mAChR binding sites returned to their original values with a t1/2 of approximately 80 min and 6 hr, respectively. The carbachol-elicited loss of m2- and m3-mAChR mRNA was blocked by their corresponding receptor subtype-specific antagonists, AF-DX 116 (M2-selective) and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) (m3-selective), and was concurrent with an increase in c-fos mRNA levels. Exposure of granule cells to the nonselective mAChR antagonist, atropine, caused a time- and concentration-dependent increase in the level of both M2- and M3-mAChR mRNA and mAChR binding sites. At 24 hr, immunoprecipitable M3-mAChR protein was predominantly increased. The atropine-induced up-regulation Of M3-mAChR mRNA was concurrent with a marked enhancement of the mRNA stability and its transcription rate. The elevated levels of m3-mAChR mRNA and binding sites declined to their untreated values after the removal of atropine. Treatment with AF-DX 116 and 4-DAMP also produced an increase in the level of M2- and m3-mAChR mRNA and their corresponding immunoprecipitable receptor protein. These results demonstrate that the mAChR agonist and antagonist induce a down- and up-regulation of mAChR expression, respectively, through receptor-mediated mechanisms in cerebellar granule cells. Moreover, at least for M3-mAChR mRNA, the agonist-and antagonist-induced effects are reversible and associated with corresponding changes in the transcription rate of this receptor mRNA species. C1 NIMH,BIOL PSYCHIAT BRANCH,MOLEC NEUROBIOL SECT,BLDG 10,RM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 40 TC 55 Z9 56 U1 0 U2 3 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 1993 VL 44 IS 5 BP 940 EP 949 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MH876 UT WOS:A1993MH87600006 PM 8246917 ER PT J AU MCKINNON, RA BURGESS, WM GONZALEZ, FJ MCMANUS, ME AF MCKINNON, RA BURGESS, WM GONZALEZ, FJ MCMANUS, ME TI METABOLIC DIFFERENCES IN COLON MUCOSAL CELLS SO MUTATION RESEARCH LA English DT Article DE COLON MUCOSAL CELLS; CYTOCHROMES P450; CYP GENES ID HUMAN-LIVER MICROSOMES; EXTRAHEPATIC TISSUES; CYTOCHROME-P-450; ACTIVATION; EXPRESSION; RABBIT; CDNA; LOCALIZATION; SEQUENCE; LUNG AB The colonic expression of cytochromes P450 from the CYP1A, CYP3A and CYP4B subfamilies has been characterized in rabbit and human tissues using RNA blotting, immunoblotting, immunohistochemistry and hybridization histochemistry. These studies demonstrate negligible expression of the CYP1A subfamily in either rabbit or human colon. The CYP3A6 gene is expressed in rabbit colon although at markedly reduced levels relative to liver and small intestine. Whilst at least two CYP3A genes are expressed at the mRNA level in human colon tissue from some individuals, no expression was demonstrated in others. Where expression was observed, this expression was continuous throughout the length of the colon. In rabbits, CYP4B1 represents a major colon P450 enzyme, expressed at levels in colon comparable to liver and small intestine. In contrast, the human CYP4B1 gene is expressed at low levels in some individuals. These studies highlight individual differences in the expression of cytochrome P450 enzymes of importance in procarcinogen metabolism. C1 UNIV QUEENSLAND,DEPT PHYSIOL & PHARMACOL,ST LUCIA,QLD 4067,AUSTRALIA. NIH,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. FLINDERS UNIV S AUSTRALIA,DEPT CLIN PHARMACOL,BEDFORD PK,SA 5042,AUSTRALIA. RI McKinnon, Ross /B-9340-2009 OI McKinnon, Ross /0000-0002-3725-793X NR 28 TC 17 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD NOV PY 1993 VL 290 IS 1 BP 27 EP 33 DI 10.1016/0027-5107(93)90029-F PG 7 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA ME719 UT WOS:A1993ME71900004 PM 7694095 ER PT J AU ZEIGER, E AF ZEIGER, E TI MUTAGENICITY OF CHEMICALS ADDED TO FOODS SO MUTATION RESEARCH LA English DT Article DE SALMONELLA; AMES TEST; FOOD ADDITIVES; US-FDA; ALDEHYDES; INORGANICS; FREE RADICALS ID NATIONAL-TOXICOLOGY-PROGRAM; RODENT CARCINOGENICITY; SALMONELLA; TESTS; CLASSIFICATION; LEVEL AB Much attention has recently been brought to the fact that many natural components of the diet are mutagenic and/or carcinogenic. Approximately 2700 distinct chemical entities, chemical mixtures, and plant extracts are allowed as direct food additives by the US F.D.A. These include chemicals found in the body, natural components of foods, and synthetic chemicals. In addition to the chemicals among these additives that are mutagenic, there are a number of mutagens that are normally present in the plant products that are consumed as part of the normal diets. The mutagenicity in Salmonella of these food additives was identified using the National Toxicology Program and US E.P.A. Gene-Tox databases. Relatively few of the chemicals deliberately added to foods have been tested for mutagenicity. Among the chemicals tested, approximately 15% were mutagenic in Salmonella. The mutagens include both organic and inorganic substances. Many of the natural plant components, such as flavonoids, hydrazides, and tannins also have been shown to be mutagenic. However, these natural components are not considered as food additives. A large proportion of the mutagenic food additives appear to act through the generation of oxygen- or free radicals. Although the relationships between mutagenicity and carcinogenicity of electrophilic chemicals has been well studied, the potential hazard of low-level increases in free-radical generating substances on tumor incidences is unknown. RP ZEIGER, E (reprint author), NIEHS A0-01,ENVIRONM TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 24 TC 19 Z9 20 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD NOV PY 1993 VL 290 IS 1 BP 53 EP 61 DI 10.1016/0027-5107(93)90032-B PG 9 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA ME719 UT WOS:A1993ME71900007 PM 7694099 ER PT J AU FRIEDMAN, E GEJMAN, PV MARTIN, GA MCCORMICK, F AF FRIEDMAN, E GEJMAN, PV MARTIN, GA MCCORMICK, F TI NONSENSE MUTATIONS IN THE C-TERMINAL SH2 REGION OF THE GTPASE-ACTIVATING PROTEIN (GAP) GENE IN HUMAN TUMORS SO NATURE GENETICS LA English DT Article ID GRADIENT GEL-ELECTROPHORESIS; POLYMERASE CHAIN-REACTION; CYTOPLASMIC SIGNALING PROTEINS; SINGLE-BASE CHANGES; SACCHAROMYCES-CEREVISIAE; TYROSINE KINASES; MAMMALIAN GAP; DNA FRAGMENTS; RAS PROTEINS; SKIN CANCERS AB GTPase Activating Protein (GAP) is involved in down-regulating normal ras proteins and in the signal transduction pathway of some growth factors. We have screened 188 human tumours for mutations in the catalytic domain and at the C terminal SH2 region GAP. Three nonsense mutations in basal cell carcinomas were detected in the SH2 region and no mutations could be demonstrated in the catalytic domain. We conclude that mutations in the SH2 region of GAP may play a role in tumorigenesis and that inactivating mutations of the GAP catalytic domain do not contribute to tumour development. C1 NIMH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. ONYX PHARMACEUT,RICHMOND,CA 94806. RP FRIEDMAN, E (reprint author), KAROLINSKA HOSP,DEPT CLIN GENET,POB 60500,S-10401 STOCKHOLM 60,SWEDEN. NR 52 TC 47 Z9 51 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 1993 VL 5 IS 3 BP 242 EP 247 DI 10.1038/ng1193-242 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA MF122 UT WOS:A1993MF12200013 PM 8275088 ER PT J AU STRONG, TV TAGLE, DA VALDES, JM ELMER, LW BOEHM, K SWAROOP, M KAATZ, KW COLLINS, FS ALBIN, RL AF STRONG, TV TAGLE, DA VALDES, JM ELMER, LW BOEHM, K SWAROOP, M KAATZ, KW COLLINS, FS ALBIN, RL TI WIDESPREAD EXPRESSION OF THE HUMAN AND RAT HUNTINGTONS-DISEASE GENE IN BRAIN AND NONNEURAL TISSUES SO NATURE GENETICS LA English DT Article ID STRIATAL PROJECTION NEURONS AB We have used RNA in situ hybridization to study the regional expression of the Huntington's disease gene (HD) and its rat homologue in brain and selected nonneural tissues. The HD transcript was expressed throughout the brain in both rat and human, especially in the neurons of the dentate gyrus and pyramidal neurons of the hippocampal formation, cerebellar granule cell layer, cerebellar Purkinje cells and pontine nuclei. Other brain areas expressed lower levels of the HD transcript without pronounced regional differences. Neuronal expression predominated over glial expression in all regions. HD mRNA was also expressed in colon, liver, pancreas and testes. The regional specificity of neuropathology in HD, which is most prominent in the basal ganglia, thus cannot be accounted for by the pattern of expression of HD. C1 UNIV MICHIGAN,DEPT INTERNAL MED,DIV MOLEC MED & GENET,4570 MSRB II,ANN ARBOR,MI 48109. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. UNIV MICHIGAN,DEPT NEUROL,ANN ARBOR,MI 48104. UNIV MICHIGAN,DEPT HUMAN GENET,ANN ARBOR,MI 48109. UNIV MICHIGAN,CELL & MOLEC BIOL PROGRAM,ANN ARBOR,MI 48109. OI Kaatz, Kevin/0000-0002-7890-4865 FU NHGRI NIH HHS [HG 00067-01]; NINDS NIH HHS [NS 01300, NS 19613] NR 23 TC 282 Z9 287 U1 0 U2 6 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 1993 VL 5 IS 3 BP 259 EP 265 DI 10.1038/ng1193-259 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA MF122 UT WOS:A1993MF12200016 PM 8275091 ER PT J AU KIESEWETTER, S MACEK, M DAVIS, C CURRISTIN, SM CHU, CS GRAHAM, C SHRIMPTON, AE CASHMAN, SM TSUI, LC MICKLE, J AMOS, J HIGHSMITH, WE SHUBER, A WITT, DR CRYSTAL, RG CUTTING, GR AF KIESEWETTER, S MACEK, M DAVIS, C CURRISTIN, SM CHU, CS GRAHAM, C SHRIMPTON, AE CASHMAN, SM TSUI, LC MICKLE, J AMOS, J HIGHSMITH, WE SHUBER, A WITT, DR CRYSTAL, RG CUTTING, GR TI A MUTATION IN CFTR PRODUCES DIFFERENT PHENOTYPES DEPENDING ON CHROMOSOMAL BACKGROUND SO NATURE GENETICS LA English DT Article ID CYSTIC-FIBROSIS GENE; CONDUCTANCE REGULATOR GENE; LINKAGE DISEQUILIBRIUM; DELTA-F508 MUTATION; IDENTIFICATION; MARKER AB Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene but the association between mutation (genotype) and disease presentation (phenotype) is not straightforward. We have been investigating whether variants in the CFTR gene that alter splicing efficiency of exon 9 can affect the phenotype produced by a mutation. A missense mutation, R117H, which has been observed in three phenotypes, was found to occur on two chromosome backgrounds with intron 8 variants that have profoundly different effects upon splicing efficiency. A close association is shown between chromosome background of the R117H mutation and phenotype. These findings demonstrate that the genetic context in which a mutation occurs can play a significant role in determining the type of illness produced. C1 JOHNS HOPKINS UNIV,SCH MED,CTR MED GENET,DEPT PEDIAT & MED,BALTIMORE,MD 21287. HOSP SICK CHILDREN,DEPT GENET,TORONTO M5G 1X8,ONTARIO,CANADA. NHLBI,PULM BRANCH,BETHESDA,MD 20892. UNIV EDINBURGH,HUMAN GENET UNIT,EDINBURGH EH8 9YL,MIDLOTHIAN,SCOTLAND. UNIV DUBLIN TRINITY COLL,DEPT GENET,DUBLIN 2,IRELAND. REG GENET CTR,BELFAST,NORTH IRELAND. BOSTON UNIV,SCH MED,CTR HUMAN GENET,BOSTON,MA 02118. UNIV N CAROLINA,DEPT PATHOL,CHAPEL HILL,NC 27599. INTEGRATED GENET INC,FRAMINGHAM,MA 01701. KAISER PERMANENTE,DEPT GENET,SAN JOSE,CA 95119. JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21287. RI Highsmith, William/B-6175-2008; Tsui, Lap-chee/A-1081-2010 NR 34 TC 322 Z9 324 U1 0 U2 7 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 1993 VL 5 IS 3 BP 274 EP 278 DI 10.1038/ng1193-274 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA MF122 UT WOS:A1993MF12200019 PM 7506096 ER PT J AU MISHKIN, M AF MISHKIN, M TI NEURAL CIRCUITRY UNDERLYING BEHAVIORAL DEFICITS IN AGING SO NEUROBIOLOGY OF AGING LA English DT Article RP MISHKIN, M (reprint author), NIMH,NEUROPSYCHOL LAB,BLDG 49,ROOM 1B80,BETHESDA,MD 20892, USA. NR 0 TC 5 Z9 5 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 1993 VL 14 IS 6 BP 615 EP 617 DI 10.1016/0197-4580(93)90047-F PG 3 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA MH158 UT WOS:A1993MH15800015 PM 8295664 ER PT J AU INGRAM, DK LANE, MA CUTLER, RG ROTH, GS AF INGRAM, DK LANE, MA CUTLER, RG ROTH, GS TI LONGITUDINAL-STUDY OF AGING IN MONKEYS - EFFECTS OF DIET RESTRICTION SO NEUROBIOLOGY OF AGING LA English DT Article RP INGRAM, DK (reprint author), NIA,GERONTOL RES CTR,MOLEC PHYSIOL & GENET SECT,BALTIMORE,MD 21224, USA. NR 0 TC 7 Z9 7 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 1993 VL 14 IS 6 BP 687 EP 688 DI 10.1016/0197-4580(93)90072-J PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA MH158 UT WOS:A1993MH15800040 PM 8295688 ER PT J AU MCARTHUR, JC HOOVER, DR BACELLAR, H MILLER, EN COHEN, BA BECKER, JT GRAHAM, NMH MCARTHUR, JH SELNES, OA JACOBSON, LP VISSCHER, BR CONCHA, M SAAH, A PALENICEK, J ARMENIAN, H FARZADEGAN, H MARGOLICK, J PHAIR, JP CHMIEL, JS BAUER, K VARIAKOJIS, D WESCH, J WOLINSKY, SM DETELS, R CHEN, I DUDLEY, J FAHEY, JL GIORGI, JV MARTINEZMAZA, O NISHANIAN, P TAYLOR, J ZACK, J RINALDO, CR KINGSLEY, L GUPTA, P HO, M MUNOZ, A BEATY, T GALAI, N MEINERT, C NELSON, K PIANTADOSI, S SEMINARA, D SU, S SCHRAGER, L VERMUND, SH KASLOW, RA VANRADEN, MJ OBRAMS, I AF MCARTHUR, JC HOOVER, DR BACELLAR, H MILLER, EN COHEN, BA BECKER, JT GRAHAM, NMH MCARTHUR, JH SELNES, OA JACOBSON, LP VISSCHER, BR CONCHA, M SAAH, A PALENICEK, J ARMENIAN, H FARZADEGAN, H MARGOLICK, J PHAIR, JP CHMIEL, JS BAUER, K VARIAKOJIS, D WESCH, J WOLINSKY, SM DETELS, R CHEN, I DUDLEY, J FAHEY, JL GIORGI, JV MARTINEZMAZA, O NISHANIAN, P TAYLOR, J ZACK, J RINALDO, CR KINGSLEY, L GUPTA, P HO, M MUNOZ, A BEATY, T GALAI, N MEINERT, C NELSON, K PIANTADOSI, S SEMINARA, D SU, S SCHRAGER, L VERMUND, SH KASLOW, RA VANRADEN, MJ OBRAMS, I TI DEMENTIA IN AIDS PATIENTS - INCIDENCE AND RISK-FACTORS SO NEUROLOGY LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; TUMOR-NECROSIS-FACTOR; HOMOSEXUAL MEN; VIRUS INFECTION; UNITED-STATES; HIV-INFECTION; SAN-FRANCISCO; FACTOR-ALPHA; COHORT; ZIDOVUDINE AB We determined incidence and future projections of dementia after AIDS onset in 492 homosexual men with AIDS in the Baltimore/Los Angeles sites of the Multicenter AIDS Cohort Study, 64 of whom developed dementia. We studied various risk factors for dementia, including demographic and clinical features, medical history, markers of immune status before AIDS, and zidovudine use. During the first 2 years after AIDS, HIV dementia developed at an annual rate of 7%. Overall, 15% of the cohort followed through death developed dementia. The median survival after dementia was 6.0 months. Using a proportional hazards model, risk factors for more rapid development of dementia were lower hemoglobin (relative hazard, 0.59 per additional 2 g/dl; p = 0.0005) and body mass index (relative hazard, 0.64 per additional 5 kg/M2; p = 0.05) 1 to 6 months before AIDS, more constitutional symptoms 7 to 12 months before AIDS (relative hazard, 1.68 per additional symptom, p = 0.005), and older age at AIDS onset (relative hazard, 1.60 per decade older; p = 0.009). In a multivariate model, pre-AIDS hemoglobin remained the most significant predictor of dementia. There were no significant risks defined from demographic characteristics, specific AIDS-defining illnesses, zidovudine use before AIDS, or CD4+ lymphocyte count before AIDS. We project that 12 months after the first AIDS diagnosis, 7.1% of survivors will have dementia. The observed association between anemia, low weight, constitutional symptoms, and dementia suggests a role for cytokines inducing both systemic and neurologic disease. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21218. UNIV CALIF LOS ANGELES,INST NEUROPSYCHIAT,LOS ANGELES,CA 90024. NORTHWESTERN UNIV,SCH MED,DEPT NEUROL,CHICAGO,IL 60611. UNIV PITTSBURGH,SCH MED,DEPT PSYCHIAT,PITTSBURGH,PA 15261. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,DEPT EPIDEMIOL,LOS ANGELES,CA 90024. NORTHWESTERN UNIV,SCH MED,HOWARD BROWN MEM CLIN,CHICAGO,IL 60611. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,PITTSBURGH,PA 15260. NIAID,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. RI Wolinsky, Steven/B-2893-2012 FU NIAID NIH HHS [AI-32535, AI-72634, AI-72676] NR 47 TC 494 Z9 509 U1 0 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 1993 VL 43 IS 11 BP 2245 EP 2252 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA MH652 UT WOS:A1993MH65200018 PM 8232937 ER PT J AU TORO, C PASCUALLEONE, A DEUSCHL, G TATE, E PRANZATELLI, MR HALLETT, M AF TORO, C PASCUALLEONE, A DEUSCHL, G TATE, E PRANZATELLI, MR HALLETT, M TI CORTICAL TREMOR - A COMMON MANIFESTATION OF CORTICAL MYOCLONUS SO NEUROLOGY LA English DT Article ID REFLEX MYOCLONUS; ORIGIN AB Ten patients, three with postural tremor and seven with action myoclonus, had stereotyped involuntary rhythmic movements when attempting to execute a sustained isometric muscle contraction. The movements were characterized by rhythmic EMG bursts lasting less than 50 msec and appearing synchronously in agonist and antagonist muscles at a rate of 9 to 18 Hz. Backaveraging of the EEG activity related to the onset of the rhythmic EMG bursts identified a cortical potential preceding the EMG bursts in all patients. These symptoms and signs fit the description of ''cortical tremor,'' a variant of cortical reflex myoclonus. Cortical tremor is common in patients with cortical myoclonus and may be a source of functional disability. In two patients in whom we studied the effects of graded levels of isometric force, force recruitment modulated the abnormal EMG bursting frequency, amplitude, and spatial distribution of the myoclonic jerks in the activated limb. Transcranial magnetic and electrical stimulation, but not peripheral nerve stimulation, influenced the abnormal EMG bursting pattern, implying a greater dependence of this rhythmic phenomenon on a central generator than on peripheral feedback loops. C1 NINCDS,HUMAN MOTOR CONTROL SECT,BLDG 10,ROOM 5N226,BETHESDA,MD 20892. NINCDS,MED NEUROL BRANCH,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,WASHINGTON,DC. RI Pascual-Leone, Alvaro/G-6566-2011; Deuschl, Gunther/A-7986-2010 NR 10 TC 69 Z9 71 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 1993 VL 43 IS 11 BP 2346 EP 2353 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA MH652 UT WOS:A1993MH65200037 PM 8232954 ER PT J AU LEHESJOKI, AE ELDRIDGE, R ELDRIDGE, J WILDER, BJ DELACHAPELLE, A AF LEHESJOKI, AE ELDRIDGE, R ELDRIDGE, J WILDER, BJ DELACHAPELLE, A TI PROGRESSIVE MYOCLONUS EPILEPSY OF UNVERRICHT-LUNDBORG TYPE - A CLINICAL AND MOLECULAR-GENETIC STUDY OF A FAMILY FROM THE UNITED-STATES WITH 4 AFFECTED SIBS SO NEUROLOGY LA English DT Note AB We describe clinical and molecular genetic data on a family from the United States in which four of five sibs are affected with progressive myoclonus epilepsy of Unverricht-Lundborg type. The gene for this disorder (EPM1) has previously been mapped to the distal region of chromosome 21. Molecular genetic results suggest that the disease gene in this family is linked to the same region of chromosome 21. Crossover events in the family help refine the gene localization by placing EPM1 between loci CBS and D21S112. C1 FOLKHALSAN INST GENET,HELSINKI,FINLAND. NCI,CLIN EPIDEMIOL BRANCH,CLIN GENET SECT,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. VET ADM HOSP MED CTR,GAINESVILLE,FL. UNIV FLORIDA,COLL MED,GAINESVILLE,FL 32611. RP LEHESJOKI, AE (reprint author), UNIV HELSINKI,DEPT MED GENET,POB 21,HAARTMANINKATU 3,SF-00014 HELSINKI,FINLAND. NR 10 TC 20 Z9 21 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 1993 VL 43 IS 11 BP 2384 EP 2386 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA MH652 UT WOS:A1993MH65200046 PM 8232963 ER PT J AU LI, SH SCHILLING, G YOUNG, WS LI, XJ MARGOLIS, RL STINE, OC WAGSTER, MV ABBOTT, MH FRANZ, ML RANEN, NG FOLSTEIN, SE HEDREEN, JC ROSS, CA AF LI, SH SCHILLING, G YOUNG, WS LI, XJ MARGOLIS, RL STINE, OC WAGSTER, MV ABBOTT, MH FRANZ, ML RANEN, NG FOLSTEIN, SE HEDREEN, JC ROSS, CA TI HUNTINGTONS-DISEASE GENE (IT-15) IS WIDELY EXPRESSED IN HUMAN AND RAT-TISSUES SO NEURON LA English DT Article ID BULBAR MUSCULAR-ATROPHY; STRIATAL NEURONS; REPEAT; PROTEIN; CORTEX AB Huntington's Disease (HD) is notable for selective neuronal vulnerability in the basal ganglia and cerebral cortex. We have investigated in human and rodent tissues the expression of the gene (IT15) whose mutation causes HD. IT15 is widely expressed, with highest levels of expression in brain, but also in lung, testis, ovary, and other tissues. Within the brain, expression is widespread with a neuronal pattern and is not enriched in the basal ganglia. Expression of IT15 is not reduced in the brain of HD patients when corrected for actin (though it is slightly decreased in the striatum when uncorrected, consistent with neuronal loss). Thus, the widespread distribution of IT15 expression does not correspond with the restricted distribution of neuropathologic changes in HD. We suggest that pathophysiology may relate to abnormal cell type-specific protein interactions of the HD protein. C1 JOHNS HOPKINS UNIV,SCH MED,MOLEC NEUROBIOL LAB,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,NEUROPATHOL LAB,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RI Young, W Scott/A-9333-2009; Ross, Christopher/H-8395-2013 OI Young, W Scott/0000-0001-6614-5112; FU NINDS NIH HHS [NS 16375] NR 38 TC 208 Z9 210 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD NOV PY 1993 VL 11 IS 5 BP 985 EP 993 DI 10.1016/0896-6273(93)90127-D PG 9 WC Neurosciences SC Neurosciences & Neurology GA MJ041 UT WOS:A1993MJ04100019 PM 8240819 ER PT J AU MCCUNE, SK VOIGT, MM HILL, JM AF MCCUNE, SK VOIGT, MM HILL, JM TI EXPRESSION OF MULTIPLE ALPHA-ADRENERGIC RECEPTOR SUBTYPE MESSENGER-RNAS IN THE ADULT-RAT BRAIN SO NEUROSCIENCE LA English DT Article ID ALPHA-2-ADRENERGIC RECEPTOR; MOLECULAR-CLONING; ALPHA-1-ADRENERGIC RECEPTOR; RIBONUCLEIC-ACID; CDNA; GENE; CLONIDINE; HETEROGENEITY; PHYSIOLOGY; MORPHINE AB Multiple subtypes of alpha adrenergic receptors with CNS expression (alpha(1A), alpha(1B), alpha(2A) and alpha(2C)) have been identified through pharmacological and molecular biological means. To characterize the localization of these subtypes and attempt to correlate subtype expression with physiological significance, the expression of the mRNAs encoding the alpha(1A), alpha(1B), alpha(2A) and alpha(2C) adrenergic receptor subtypes was examined in the adult rat brain by in situ hybridization histochemistry. Each subtype demonstrated a unique pattern of distribution, with the alpha(1) adrenergic receptors more restricted in their distribution and the alpha(2) receptor more widespread. The alpha(1A) was primarily localized in the olfactory bulb, intermediate layers of the cortex, the hippocampus and the reticular nucleus of the thalamus. The alpha(1B) was expressed in intermediate and deep layers of the cortex, thalamus, hippocampus, dorsal raphe and cerebellum. Although the alpha(2A) message was relatively low in abundance, it was identified in the olfactory bulb, cortex, hippocampus, locus coeruleus, pons and cerebellum. The alpha(2C) messenger RNA was localized in the cortex (particularly cingulate), hippocampus, caudoputamen, pons and cerebellum. Multiple alpha adrenergic receptor subtypes have significant sequence homology and similar pharmacologic properties; however, they each possess a unique pattern of messenger RNA distribution throughout the brain. The multiplicity of subtypes of alpha adrenergic receptors in specific brain regions may dictate the physiological and pharmacological responses to catecholamines. C1 NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD 20892. NATL UNIV IRELAND UNIV COLL DUBLIN,DEPT PHARMACOL,DUBLIN 4,IRELAND. RP MCCUNE, SK (reprint author), GEORGE WASHINGTON UNIV,CHILDRENS NATL MED CTR,DEPT NEONATOL,WASHINGTON,DC 20010, USA. NR 43 TC 116 Z9 118 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 1993 VL 57 IS 1 BP 143 EP 151 DI 10.1016/0306-4522(93)90116-W PG 9 WC Neurosciences SC Neurosciences & Neurology GA ME548 UT WOS:A1993ME54800010 PM 8278048 ER PT J AU CAMERA, L KINUYA, S GARMESTANI, K PAI, LH BRECHBIEL, MW GANSOW, OA PAIK, CH PASTAN, I CARRASQUILLO, JA AF CAMERA, L KINUYA, S GARMESTANI, K PAI, LH BRECHBIEL, MW GANSOW, OA PAIK, CH PASTAN, I CARRASQUILLO, JA TI EVALUATION OF A NEW DTPA-DERIVATIVE CHELATOR - COMPARATIVE BIODISTRIBUTION AND IMAGING STUDIES OF IN-111 LABELED B3 MONOCLONAL-ANTIBODY IN ATHYMIC MICE BEARING HUMAN EPIDERMOID CARCINOMA XENOGRAFTS SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article ID NUDE-MICE; HEPATIC-UPTAKE; NORMAL TISSUE; TUMOR; IN-111; ANTIGEN; PHARMACOKINETICS; METABOLISM; LIVER; LOCALIZATION AB Biodistribution and imaging characteristics of monoclonal antibody (MAb) B3 conjugated to either the 2-(p-isothiocyanatobenzyl)-cyclohexyl-DTPA (CHX-B) or 2-(p-isothiocyanatobenzyl)-6-methyl-DTPA (1B4M) and labeled with In-111, were evaluated in nude mice bearing A431 human epidermoid carcinoma xenografts. MAb B3, is a murine IgG1k reacting with a carbohydrate antigen abundantly expressed by most carcinomas. Both In-111-(CHX-B)-B3 and In-111-(1B4M)-B3 showed good tumor targeting with peak values observed at 72 h with 27.6 +/- 7.6 and 25.4 +/- 1.7% ID/g, respectively (P > 0.05). High tumor-to-organ ratios were also observed and, confirmed by the imaging results. In particular, tumor-to-liver ratios increased from 5.0 +/- 0.9 at 24 h to 9.2 +/- 2.0 at 168 h for In-111-(CHX-B)-B3 and from 4.5 +/- 0.6 to 8.9 +/- 3.5 for In-111-(1B4M)-B3. This was mainly the result of low liver accumulation of both In-111-(CHX-B)-B3 and In-111-(1B4M)-B3, with only 2.48 +/- 0.46 and 2.5 +/- 0.9% ID/g at 168 h, respectively (P > 0.05). Our findings indicate that either CHX-B or 1B4M can be successfully used for In-111-labeling of MAbs and that In-111-B3 may represent a promising radioimmunoimaging agent. C1 NCI,WARREN G MAGNUSON CLIN CTR,DEPT NUCL MED,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. RI Carrasquillo, Jorge/E-7120-2010 NR 41 TC 20 Z9 20 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0883-2897 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD NOV PY 1993 VL 20 IS 8 BP 955 EP 962 DI 10.1016/0969-8051(93)90096-D PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA MH355 UT WOS:A1993MH35500009 PM 8298575 ER PT J AU SORKIN, A DIFIORE, PP CARPENTER, G AF SORKIN, A DIFIORE, PP CARPENTER, G TI THE CARBOXYL-TERMINUS OF EPIDERMAL GROWTH-FACTOR RECEPTOR/ERBB-2 CHIMERAE IS INTERNALIZATION IMPAIRED SO ONCOGENE LA English DT Article ID TYROSINE KINASE-ACTIVITY; EGF RECEPTOR; DOWN-REGULATION; A431 CELLS; HUMAN-FIBROBLASTS; ENDOCYTIC SYSTEM; CARCINOMA-CELLS; NEU ONCOGENE; GENE; PROTEIN AB The endocytosis of gp185erbB-2 was studied using chimeric receptors in which the intracellular domain of erbB-2, or subdomains thereof, was substituted for the corresponding regions of the epidermal growth factor (EGF) receptor. Chimeric and wild-type EGF or erbB-2 receptors were expressed in mouse NIH3T3 or NR6 fibroblasts and in a human mammary adenocarcinoma cell line, MDAMB-134. The rate of EGF-induced internalization for the chimera consisting of the extracellular EGF receptor domain and intracellular erbB-2 domain was reduced three- to fourfold compared with the wild-type EGF receptor. The low rate of internalization of the chimeric receptor resulted in impaired down-regulation and degradation of the receptor. Substitution of the carboxyl terminus of erhB-2 for the corresponding region of the EGF receptor caused a similar decrease of receptor endocytosis, whereas substitution of the erhB-2 tyrosine kinase domain did not affect internalization and down-regulation. Since the tyrosine kinase of the internalization-defective chimeric receptors could be activated by EGF, kinase activity and autophosphorylation of erhB-2 do not appear to be sufficient for a maximum rapid internalization of the chimeric receptors. These results suggest that the carboxyl terminus of erhB-2 either does not possess all the signals required for the rapid internalization or contains an inhibitory signal for rapid internalization. C1 VANDERBILT UNIV, MED CTR, SCH MED, DEPT MED, NASHVILLE, TN 37232 USA. NCI, CELLULAR & MOLEC BIOL LAB, BETHESDA, MD 20892 USA. RP SORKIN, A (reprint author), VANDERBILT UNIV, MED CTR, SCH MED, DEPT BIOCHEM, NASHVILLE, TN 37232 USA. RI Di Fiore, Pier Paolo/K-2130-2012 OI Di Fiore, Pier Paolo/0000-0002-2252-0950 FU NCI NIH HHS [CA24071] NR 47 TC 88 Z9 88 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 1993 VL 8 IS 11 BP 3021 EP 3028 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA MC093 UT WOS:A1993MC09300016 PM 8105439 ER PT J AU REID, RL LINDHOLM, PF MIRESKANDARI, A DITTMER, J BRADY, JN AF REID, RL LINDHOLM, PF MIRESKANDARI, A DITTMER, J BRADY, JN TI STABILIZATION OF WILD-TYPE P53 IN HUMAN T-LYMPHOCYTES TRANSFORMED BY HTLV-I SO ONCOGENE LA English DT Article ID CELLULAR TUMOR-ANTIGEN; VIRUS TYPE-I; HUMAN PAPILLOMAVIRUS TYPE-16; CORD BLOOD-LYMPHOCYTES; MONOCLONAL-ANTIBODIES; LEUKEMIA LYMPHOMA; SV40-TRANSFORMED CELLS; ACTIVATING MUTATIONS; INCREASED EXPRESSION; MOLECULAR-CLONING AB Adult T-cell leukemia/lymphoma is an aggressive malignancy associated with infection by the human T-lymphotropic virus type-I (HTLV-1). We now demonstrate that p53 expression is elevated in the HTLV-1-transformed T-lymphocyte lines C81, MT-2, MT-4 and HUT 102. In pulse-chase experiments, the p53 protein demonstrated a prolonged half-life of 2 to 8 h in HTLV-1-transformed cells compared with 0.5 to 1.0 h for wild-type p53 in primary human and murine fibroblasts, or human peripheral blood lymphocytes. In cell lines C81 and HUT 102, which exhibited the longest p53 protein half-life, the wild-type-related PAb1620 epitope was detected at reduced levels. The PAb240 mutant-related p53 epitope was not detected in any of the transformed cell lines. By direct sequence analysis of RT-PCR products, the entire p53 cDNA coding sequence was determined to be wild-type in all four cell lines. Stabilization of wild-type p53 may represent its functional inactivation and contribute to lymphocyte transformation by HTLV-I. C1 NCI,MOLEC VIROL LAB,BLDG 41,ROOM B602,BETHESDA,MD 20892. RI Dittmer, Juergen/G-1160-2011 NR 73 TC 96 Z9 97 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV PY 1993 VL 8 IS 11 BP 3029 EP 3036 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA MC093 UT WOS:A1993MC09300017 PM 8414503 ER PT J AU SHAUGHNESSY, JD OWENS, JD WIENER, F HILBERT, DM HUPPI, K POTTER, M MUSHINSKI, JF AF SHAUGHNESSY, JD OWENS, JD WIENER, F HILBERT, DM HUPPI, K POTTER, M MUSHINSKI, JF TI RETROVIRAL ENHANCER INSERTION 5' OF C-MYC IN 2 TRANSLOCATION-NEGATIVE MOUSE PLASMACYTOMAS UP-REGULATES C-MYC EXPRESSION TO DIFFERENT EXTENTS SO ONCOGENE LA English DT Article ID MURINE LEUKEMIA-VIRUS; MESSENGER-RNA; DNA FRAGMENTS; TRANSCRIPTIONAL ACTIVATION; CHROMOSOME TRANSLOCATIONS; NUCLEOTIDE-SEQUENCE; AGAROSE GELS; T-LYMPHOMAS; ONC GENE; V-ABL AB Essentially all murine plasmacytomas have deregulated c-myc expression that is typically brought about by chromosomal translocations between the c-myc/Pvt-1 locus and one of the immunoglobulin loci. ABPC 22 and RFPC 2782 are BALB/c plasmacytomas that lack chromosomal translocations yet have Southern blot evidence of c-myc gene rearrangements. In this report we show that proviral integrations 5' of the c-myc gene can deregulate c-myc expression in mouse plasmacytomas. Analysis of DNA sequences 5' of the c-myc genes from both tumors demonstrated that rearrangements were caused by retroviral integrations 5' of c-myc exon 1. The proviral insertion in RFPC 2782 was associated with a high steady-state c-myc mRNA level comparable to that seen in plasmacytomas with typical translocations. An analogous proviral insertion in ABPC 22 was associated with a c-myc RNA level that was only 38% of that of RFPC 2782. Nuclear run-on studies of c-myc transcription showed that ABPC 22 has both a lower rate of transcription and a greater degree of transcriptional attenuation than RFPC 2782. DNA sequencing of the long terminal repeat of each tumor provirus showed that the ABPC 22 provirus harbors a deletion of one of the two direct repeats in the viral enhancer, whereas both repeats are present in the RFPC 2782 provirus. These data indicate that maximum LTR enhancer effectiveness in plasmacytomas in vivo requires the presence of both LTR direct repeats. The documentation of the low level of steady-state c-myc mRNA in ABPC 22 supports the notion that deregulated c-myc expression, even at low steady state levels, is effective in supporting the development of plasmacytomas. C1 NCI,GENET LAB,BETHESDA,MD 20892. UNIV MARYLAND,DEPT ZOOL,COLL PK,MD 20742. KAROLINSKA INST,DEPT TUMOR BIOL,S-10401 STOCKHOLM 60,SWEDEN. NR 53 TC 10 Z9 10 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV PY 1993 VL 8 IS 11 BP 3111 EP 3121 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA MC093 UT WOS:A1993MC09300028 PM 8414513 ER PT J AU TRAVERSE, S COHEN, P PATERSON, H MARSHALL, C RAPP, U GRAND, RJA AF TRAVERSE, S COHEN, P PATERSON, H MARSHALL, C RAPP, U GRAND, RJA TI SPECIFIC ASSOCIATION OF ACTIVATED MAP KINASE KINASE KINASE (RAF) WITH THE PLASMA-MEMBRANES OF RAS-TRANSFORMED RETINAL CELLS SO ONCOGENE LA English DT Article ID NERVE GROWTH-FACTOR; MURINE SARCOMA-VIRUS; PROTEIN-KINASE; MONOCLONAL-ANTIBODIES; PHOSPHORYLATION; LOCALIZATION; ONCOGENE; CASCADE; P21RAS; GENE AB Plasma membrane-enriched fractions were prepared from human embryonic retinal cells transformed with either adenovirus El A and oncogenic ras DNA, or E1A and E1B DNA. Ras comprised 5-10 % of the membrane protein from the E1A/ras transformed cells, whereas the membranes from EIA/E1B transformed cells did not overexpress Ras. The membranes from E1a/ras cells contained MAP kinase kinase kinase (MAPKKK) activity, even after washing in 0.5 M NaCl, whereas the membranes from E1A/EIB cells did not. Neither membrane fraction contained MAP kinase kinase or MAP kinase activity after washing with 0.5M NaCl. Immunoblotting experiments revealed about 10-fold more c-Raf in the membranes from EIA/ras cells than from E1A/E1B cells, and 50-60% of the MAPKKK activity in Triton X100-solubilised membranes from E1A/ras cells was immunoprecipitated with anti-Raf antibodies. A striking enrichment of c-Raf in the plasma membranes of E1A/ras cells was also demonstrated by immunocytochemistry, where it was co-localized with Ras. The MAPKKK activity in E1A/ras membranes was unaffected by incubation with protein phosphatases or by inclusion of protein phosphatase inhibitors during isolation, nor was it activated by GTP-Ras or inhibited by GDP-Ras. The results support the view that Ras and c-Raf interact with one another, but that neither c-Raf phosphorylation nor its interaction with GTP-Ras are alone sufficient for activation. The identification of MAPKKK activity in the membranes of ras-transformed cells may prove useful in elucidating the mechanism by which Raf is activated by Ras. C1 UNIV BIRMINGHAM,SCH MED,DEPT CANC STUDIES,CANC RES CAMPAIGN LABS,BIRMINGHAM B15 2TJ,W MIDLANDS,ENGLAND. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. INST CANC RES,CHESTER BEATTY LABS,LONDON SW3 6JB,ENGLAND. RP TRAVERSE, S (reprint author), UNIV DUNDEE,DEPT BIOCHEM,MRC,PROT PHOSPHORYLAT UNIT,DUNDEE DD1 4HN,SCOTLAND. NR 41 TC 105 Z9 105 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV PY 1993 VL 8 IS 11 BP 3175 EP 3181 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA MC093 UT WOS:A1993MC09300036 PM 8414521 ER PT J AU KASSOFF, A RAY, GS KREPOSTMAN, J CHANG, MM GARZA, D BUEHLER, J DYLONG, K BERGER, BB BRITT, M MURPHY, RP TURCOTTE, P ELMAN, M FERRIS, FL LERNER, BC SCHENNING, S SACKETT, C CHEW, EY OPTICAN, D SHARUK, G AIELLO, L SHAH, S RAND, L KORETZ, D RUDICH, R WEISS, J CONWAY, BP CAMPOCHAIRO, P CASADA, R JOHNSTON, R KAMINSKI, F ORTH, D FLOOD, TP PACKO, K ARREDONDO, L BRYANT, D SINGERMAN, LJ RICE, TA NOVAK, MA TEICHER, P PRESEREN, D SCHWARTZ, PL FASTENBURG, D ROSEN, D GRIFFITH, C DROUILHET, JH NOBLER, D GARCIA, CA BLOOME, MA RUIZ, RS RUIZ, NJ WEINGEIST, T SNEED, S FOUNTAIN, C CHANDRA, SR MYERS, FL BRESNICK, GH STEWART, L JABBOUR, N TAYLOR, N LIANG, JC BENNETT, TA ZIEBA, K SUMMERSON, L YANNUZZI, L DALY, J DEROSA, JT SISCO, L KINGSLEY, RM WILKINSON, CP CONNER, B ADAMS, C BRUCKER, J SANDBURG, E DOFT, BH LOBES, LA RINKOFF, J MELLINGER, K HOFFMAN, ME SORR, EM FELLER, A HANDELMAN, IL CHENOWETH, RG ROYCE, B MINCEY, GJ FLEMING, J SINGERMAN, LJ MOWERY, RP REMALEY, NA LERNER, B LUSTBADER, J KIVITZ, I FINKELSTEIN, D MAGUIRE, MG NUSSENBLATT, R PODGOR, M SEIGEL, D AF KASSOFF, A RAY, GS KREPOSTMAN, J CHANG, MM GARZA, D BUEHLER, J DYLONG, K BERGER, BB BRITT, M MURPHY, RP TURCOTTE, P ELMAN, M FERRIS, FL LERNER, BC SCHENNING, S SACKETT, C CHEW, EY OPTICAN, D SHARUK, G AIELLO, L SHAH, S RAND, L KORETZ, D RUDICH, R WEISS, J CONWAY, BP CAMPOCHAIRO, P CASADA, R JOHNSTON, R KAMINSKI, F ORTH, D FLOOD, TP PACKO, K ARREDONDO, L BRYANT, D SINGERMAN, LJ RICE, TA NOVAK, MA TEICHER, P PRESEREN, D SCHWARTZ, PL FASTENBURG, D ROSEN, D GRIFFITH, C DROUILHET, JH NOBLER, D GARCIA, CA BLOOME, MA RUIZ, RS RUIZ, NJ WEINGEIST, T SNEED, S FOUNTAIN, C CHANDRA, SR MYERS, FL BRESNICK, GH STEWART, L JABBOUR, N TAYLOR, N LIANG, JC BENNETT, TA ZIEBA, K SUMMERSON, L YANNUZZI, L DALY, J DEROSA, JT SISCO, L KINGSLEY, RM WILKINSON, CP CONNER, B ADAMS, C BRUCKER, J SANDBURG, E DOFT, BH LOBES, LA RINKOFF, J MELLINGER, K HOFFMAN, ME SORR, EM FELLER, A HANDELMAN, IL CHENOWETH, RG ROYCE, B MINCEY, GJ FLEMING, J SINGERMAN, LJ MOWERY, RP REMALEY, NA LERNER, B LUSTBADER, J KIVITZ, I FINKELSTEIN, D MAGUIRE, MG NUSSENBLATT, R PODGOR, M SEIGEL, D TI RANDOMIZED COMPARISON OF KRYPTON VERSUS ARGON SCATTER PHOTOCOAGULATION FOR DIABETIC DISC NEOVASCULARIZATION - THE KRYPTON ARGON REGRESSION NEOVASCULARIZATION STUDY REPORT NUMBER 1 SO OPHTHALMOLOGY LA English DT Article ID LASER; RETINOPATHY; FUNDUS AB Background: The Krypton Argon Regression of Neovascularization Study (KARNS) was designed to compare the efficacy of red krypton versus blue-green argon laser photocoagulation for the management of high-risk proliferative diabetic retinopathy. Methods: A prospective, randomized clinical trial was performed in 24 clinical centers. Patients (n = 696, 907 eyes) with diabetes and neovascularization of the disc (NVD) of one-third disc area or greater in extent were assigned at random to either argon or krypton laser scatter (panretinal) photocoagulation. The major endpoint of the regression of NVD to less than one-third disc area in extent at 3 months was evaluated by comparisons of gradings of the fundus photographs obtained at baseline and follow-up. Results: At 3 months' follow-up, the proportion of eyes with regression of NVD to less than or equal to one-third disc area in extent were 41.1% in the argon-treated group and 41.8% in the krypton-treated group (P = 0.92). The odds of regressing to this extent of NVD at 3 months for argon-treated eyes versus krypton-treated eyes was 0.98 (95% confidence interval, 0.74-1.31). Conclusion: Scatter laser photocoagulation with either krypton red or argon appears to be equally effective in the treatment of proliferative diabetic retinopathy with NVD. C1 NEI, BLDG 31, RM 6A52, BETHESDA, MD 20892 USA. ALBANY MED COLL, ALBANY, NY 12208 USA. JOHNS HOPKINS UNIV, BALTIMORE, MD 21218 USA. JOSLIN DIABET CTR, BOSTON, MA USA. UNIV VIRGINIA, MED CTR, CHARLOTTESVILLE, VA 22903 USA. JOHNSTON EYE CLIN, CHEYENNE, WY USA. INGALLS MEM HOSP, ILLINOIS RETINA ASSOCIATES, CHICAGO, IL USA. LONG ISL JENISH MED CTR, GREAT NECK, NY USA. HERMANN EYE CTR, HOUSTON, TX USA. UNIV IOWA, IOWA CITY, IA 52242 USA. UNIV WISCONSIN, MADISON, WI 53706 USA. W VIRGINIA UNIV, MED CTR, MORGANTOWN, WV 26506 USA. MANHATTAN EYE EAR & THROAT HOSP, NEW YORK, NY 10021 USA. DEAN MCGEE EYE INST, OKLAHOMA CITY, OK USA. UNIV PENN, SCHEIE EYE INST, PHILADELPHIA, PA 19104 USA. RETINA VITREOUS PA, PITTSBURGH, PA USA. EVERETT & HURITE, PITTSBURGH, PA USA. OREGON LIONS SIGHT & HEARING INST, PORTLAND, OR USA. CAROLINA EYE ASSOC, SOUTHERN PINES, NC USA. NR 25 TC 13 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD NOV PY 1993 VL 100 IS 11 BP 1655 EP 1664 PG 10 WC Ophthalmology SC Ophthalmology GA MF323 UT WOS:A1993MF32300029 ER PT J AU KORPARCOLIG, B POPOVIC, Z MATKOVICCALOGOVIC, D VIKICTOPIC, D AF KORPARCOLIG, B POPOVIC, Z MATKOVICCALOGOVIC, D VIKICTOPIC, D TI MERCURATION PRODUCTS OF SOME ALIPHATIC CARBOXYLIC-ACIDS - PREPARATION AND SPECTRAL PROPERTIES - CRYSTAL-STRUCTURE OF THE BIPYRIDYL COMPLEX OF THE NITRATE OF MONOMERCURATED PROPIONIC-ACID SO ORGANOMETALLICS LA English DT Note AB When propionic acid is heated with mercuric propionate the condensation polymer of the alpha-monomercurated propionic acid is obtained along with traces of the dimercurated acid. When n-butyric acid is heated with mercuric n-butyrate the condensation polymer of the alpha-monomercurated n-butyric acid is obtained together with about a 20% yield of the dimercurated one. In contrast, n-valeric and isovaleric acids are mainly dimercurated. The site of mercuration, established by H-1 and C-13 NMR spectroscopy, was confirmed by an X-ray crystal structure analysis of the 2,2-bipyridyl complex of 2-(nitratomercurio)propionic acid. The NMR spectra showed a number of long range Hg-199-H-1 (up to five bonds) and Hg-199-C-13 (up to four bonds) spin-spin couplings and the relation of three-bond Hg-199-C-13 couplings to molecular conformation. In the crystal structure of [CH3CH(Hg(C10H8N2))COOH]NO3 mercury is bonded to the alpha-carbon atom of the propionic acid at a distance of 2.11(1) angstrom and to the nitrogen atoms of the bipyridyl ligand at 2.226(9) and 2.423(7) angstrom. C1 NIDDK,ANALYT CHEM LAB,BETHESDA,MD 20892. RUDJER BOSKOVIC INST,ZAGREB 41000,CROATIA. RP KORPARCOLIG, B (reprint author), UNIV ZAGREB,FAC SCI,GEN & INORGAN CHEM LAB,ZVONIMIROVA 8,41000 ZAGREB,CROATIA. NR 19 TC 17 Z9 17 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0276-7333 J9 ORGANOMETALLICS JI Organometallics PD NOV PY 1993 VL 12 IS 11 BP 4708 EP 4713 DI 10.1021/om00035a072 PG 6 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA MH645 UT WOS:A1993MH64500072 ER PT J AU DESOUZA, CJ RUTLEDGE, PA MEIER, AH ATWATER, I AF DESOUZA, CJ RUTLEDGE, PA MEIER, AH ATWATER, I TI EFFECTS OF PULSATILE GLUCOSE STIMULI ON LONG-TERM INSULIN SECRETORY PATTERNS IN ISLETS OF LANGERHANS MICRODISSECTED FROM SYRIAN-HAMSTERS SO PANCREAS LA English DT Article ID GONADOTROPIN-RELEASING HORMONE; ULTRADIAN OSCILLATIONS; INVIVO HYPERGLYCEMIA; RAT ISLETS; INVITRO; DESENSITIZATION; CELLS; DIACYLGLYCEROL; INVOLVEMENT; MECHANISMS AB The long-term effects of continuous and pulsatile glucose stimulation of islets of Langerhans microdissected from Syrian hamsters were examined. In the presence of a continuous glucose stimulus insulin secretion peaked during the first 3 h of stimulation followed by a decrease. In the presence of 11.2 mM glucose a second smaller peak of insulin secretion was observed 14-16 h after the perifusion started. Irrespective of the glucose concentration, insulin secretion then steadily decreased and reached very low levels by the end of the 48-h perifusion. However, glucose stimulus provided in a pulsatile manner appeared to reduce this rate of decrease in insulin secretion. Thus, after 48 h, islets exposed to the pulsatile glucose stimulus showed greater insulin responsiveness to glucose than those exposed to a constant glucose stimulus. C1 LOUISIANA STATE UNIV,DEPT ZOOL & PHYSIOL,BATON ROUGE,LA 70803. NIDDK,CELL BIOL & GENET,BETHESDA,MD. NR 25 TC 2 Z9 2 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 1993 VL 8 IS 6 BP 726 EP 731 DI 10.1097/00006676-199311000-00009 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA MD188 UT WOS:A1993MD18800009 PM 8255887 ER PT J AU KRESINA, TF HE, Q ESPOSTI, SD ZERN, MA AF KRESINA, TF HE, Q ESPOSTI, SD ZERN, MA TI HEPATIC-FIBROSIS AND GENE-EXPRESSION CHANGES INDUCED BY PRAZIQUANTEL TREATMENT DURING IMMUNE MODULATION OF SCHISTOSOMA-JAPONICUM INFECTION SO PARASITOLOGY LA English DT Article DE SCHISTOSOMA JAPONICUM; FIBROGENIC GENE EXPRESSION; PRAZIQUANTEL; IMMUNE MODULATION ID GROWTH-FACTOR-BETA; GRANULOMA-FORMATION; MESSENGER-RNA; CELLS; RESPONSES; INVITRO; IDENTIFICATION; COMPLEMENTARY; DYNAMICS; ANTIGEN AB In the present study fibrogenic gene expression was determined in murine Schistosoma japonicum infection during the progression of immune modulation of infection and following chemotherapy during the course of immune modulation. Histomorphometric analysis of granuloma size and collagen deposition revealed peak granuloma size in acute infection (5 weeks) and peak hepatic collagen content at 16 weeks of infection. Peak Type I collagen gene expression was concomitant with TGF-beta 1 gene expression at 8-11 weeks. Chemotherapy during either acute (9 weeks) or chronic (24, 28 weeks) infection resulted in increased collagen deposition and increased gene expression of Type I collagen and TGF-beta 1. However, chemotherapy at 14-16 weeks resulted in decreased levels of TGF-beta 1 gene expression and essentially minimal change in Type I collagen deposition and gene expression. These data indicate that chemotherapy of schistosomiasis japonica does not reverse hepatic fibrogenesis when administered in acute infection - when granuloma size is maximal or in chronic infection. However, a beneficial effect on hepatic fibrogenesis is seen when chemotherapy is administered at 14-16 weeks post-infection, a time of decreasing granuloma size and maximal hepatic collagen content. Thus the ability to reverse schistosomal-induced hepatic fibrogenesis by chemotherapy may depend on disease stage. C1 BROWN UNIV,MIRIAM HOSP,INST INT HLTH,DEPT MED,PROVIDENCE,RI 02906. THOMAS JEFFERSON UNIV,DEPT MED,PHILADELPHIA,PA 19107. VET ADM MED CTR,DEPT MED,PROVIDENCE,RI 02906. ROGER WILLIAMS MED CTR,PROVIDENCE,RI 02906. RP KRESINA, TF (reprint author), NIDDK,DIGEST DIS & NUTR BRANCH,WESTWOOD BLDG,ROOM 3A17,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [AI29102] NR 39 TC 8 Z9 13 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0031-1820 J9 PARASITOLOGY JI Parasitology PD NOV PY 1993 VL 107 BP 397 EP 404 PN 4 PG 8 WC Parasitology SC Parasitology GA MJ755 UT WOS:A1993MJ75500006 PM 7506405 ER PT J AU MULLER, EE KOLOBOW, T MANDAVA, S JONES, M VITALE, G APRIGLIANO, M YAMADA, K AF MULLER, EE KOLOBOW, T MANDAVA, S JONES, M VITALE, G APRIGLIANO, M YAMADA, K TI HOW TO VENTILATE LUNGS AS SMALL AS 12.5-PERCENT OF NORMAL - THE NEW TECHNIQUE OF INTRATRACHEAL PULMONARY VENTILATION SO PEDIATRIC RESEARCH LA English DT Article ID CONGENITAL DIAPHRAGMATIC-HERNIA; ACUTE RESPIRATORY-FAILURE; FETAL CIRCULATION; PNEUMOTHORAX; MANAGEMENT; MORTALITY; PRESSURE; INFANTS; ADULT AB We wished to determine in a laboratory animal model how much residual lung was needed to sustain total gas exchange. In a series of young, healthy lambs weighing approximately 10 kg that were sedated and paralyzed, we progressively excluded from gas exchange all the left lung (a total of 43%), plus the right lower and cardiac lobes (81%), plus the right middle lobe (87.5%). In some studies, the respective lobes were surgically removed; in others, the bronchi and the pulmonary arteries to the respective lobes were ligated. We provided pulmonary ventilation using the pressure control mode (Servo 900 C) at a tidal volume of 20 mL/kg multiplied by the fraction of the remaining lungs, a respiratory rate up to 120/min, a peak inspiratory pressure of 12-15 cm H2O, and a positive end-expiratory pressure of 3 cm H2O. Those lambs with at least both the right upper lobe (RUL) and right middle lobe remaining (19% of total lungs) were weaned to room air on mechanical ventilation within 48 h. Ventilating RUL (12.5% of remaining lung) with the same ventilator required a substantially higher tidal volume and peak inspiratory pressure to result in adequate alveolar ventilation but led to respiratory failure and death within 8 h. We then applied a newly developed system of intratracheal pulmonary ventilation to ventilate the RUL (12.5% of remaining lung) alone. A continuous flow of humidified mixture of air and oxygen was directly passed into the trachea at the level of the carina through a diffuser at a tidal volume of 2.5 mL/kg. A single valve controlled expiration and respiratory rate. Lambs with only RUL remaining were weaned to room air within 2 h, at a respiratory rate of 60-120/min and peak inspiratory pressure of 14-9 cm H2O, inspiration to expiration ratio of 1:1, and positive end-expiratory pressure of 3 cm H2O. Initial mean pulmonary artery pressure progressively decreased from 40 +/- 5 to 25 +/- 7 mm Hg within 6 h after surgery. C1 NHLBI,LCB,PULM & CARDIAC ASSIST DEVICES SECT,BETHESDA,MD 20892. NR 26 TC 28 Z9 28 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD NOV PY 1993 VL 34 IS 5 BP 606 EP 610 PG 5 WC Pediatrics SC Pediatrics GA MD795 UT WOS:A1993MD79500010 PM 8284097 ER PT J AU NEWMAN, TB KLEBANOFF, MA AF NEWMAN, TB KLEBANOFF, MA TI NEONATAL HYPERBILIRUBINEMIA AND LONG-TERM OUTCOME - ANOTHER LOOK AT THE COLLABORATIVE PERINATAL PROJECT SO PEDIATRICS LA English DT Article DE NEONATAL JAUNDICE; BILIRUBIN; FOLLOW-UP STUDIES; INTELLIGENCE; PSYCHOMOTOR DISORDERS; SENSORINEURAL HEARING LOSS ID BILIRUBIN TOXICITY; CEREBRAL-PALSY; JAUNDICE; HEALTHY; PHOTOTHERAPY; ANTECEDENTS; NEWBORNS; INFANT AB Objective. To examine the association between neonatal bilirubin levels and subsequent neurodevelopmental outcome. Design. Prospective cohort study. Setting. 12 US medical centers from 1959 (first births) to 1974 (last follow-up). Participants. 41 324 singleton white or black infants with birth weight greater-than-or-equal-to 2500 g who had neonatal bilirubin measurements recorded and survived at least 1 year. Main outcome measures. Wechsler Intelligence Scale for Children Intelligence Quotient (IQ) at age 7 years, blinded neurologic examination at age 7 years, and sensorineural hearing loss at age 8 years. Results. There was no association between IQ and bilirubin. For example, comparing children who had maximum bilirubin levels greater-than-or-equal-to 342 mumol/L (20 mg/dL) with those who had lower bilirubin levels, adjusted mean IQs were 105.0 and 103.4 in whites (difference + 1.6; 95% confidence interval [CI]: - 0.4 to + 3.5) and 91.0 and 93.3 in blacks (difference - 2.3; 95% CI: -4.8 to + 0.2). Abnormal neurologic examination results were reported in 12 of 268 children (4.5%) with bilirubin greater-than-or-equal-to 342 mumol/L (20 mg/dL) compared with 1249 of 33 004 children (3.8%) with lower levels (relative risk [RR] = 1.2; 95% CI: 0.7 to 2.1). The frequency of abnormal or suspicious neurologic examination results increased in a stepwise fashion with increasing bilirubin level (P < .001), from 4346/29 258 (14.9%) of those with bilirubin levels <171 pmol/L (10 mg/dL) to 60/268 (22.4%) of those with bilirubin levels greater-than-or-equal-to 342 pmol/L (20 mg/dL), apparently due to increasing minor motor abnormalities at higher bilirubin levels. Sensorineural hearing loss was not associated with high bilirubin levels (RR = 1.0; 95% CI: 0.3 to 3.0). Conclusions. Neonatal bilirubin levels seem to have little effect on IQ, definite neurologic abnormalities, or hearing loss. Higher bilirubin levels are associated with minor motor abnormalities, but the clinical importance of this finding is limited by the weakness of the association, the mild nature of the abnormalities, and the lack of evidence that they are prevented by treatment. C1 UNIV CALIF SAN FRANCISCO,SCH MED,DEPT PEDIAT,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,SCH MED,DEPT EPIDEMIOL & BIOSTAT,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,SCH MED,ROBERT WOOD JOHNSON CLIN SCHOLARS PROGRAM,SAN FRANCISCO,CA 94143. NICHHD,BETHESDA,MD 20892. RP NEWMAN, TB (reprint author), UNIV CALIF SAN FRANCISCO,SCH MED,DEPT LAB MED,521 PARNASSUS AVE,RM C-259,SAN FRANCISCO,CA 94143, USA. FU PHS HHS [MCJ-060573] NR 30 TC 96 Z9 97 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 1993 VL 92 IS 5 BP 651 EP 657 PG 7 WC Pediatrics SC Pediatrics GA ME773 UT WOS:A1993ME77300002 PM 8414851 ER PT J AU CLEMENS, J RAO, M AHMED, F WARD, R HUDA, S CHAKRABORTY, J YUNUS, M KHAN, MR ALI, M KAY, B VANLOON, F SACK, D AF CLEMENS, J RAO, M AHMED, F WARD, R HUDA, S CHAKRABORTY, J YUNUS, M KHAN, MR ALI, M KAY, B VANLOON, F SACK, D TI BREAST-FEEDING AND THE RISK OF LIFE-THREATENING ROTAVIRUS DIARRHEA - PREVENTION OR POSTPONEMENT SO PEDIATRICS LA English DT Article DE BREAST-FEEDING; ROTAVIRUS; DIARRHEA ID ORAL CHOLERA VACCINES; YOUNG-CHILDREN; BANGLADESHI CHILDREN; RURAL BANGLADESH; FIELD TRIAL; GASTROENTERITIS; ANTIBODIES; DISEASES; IMMUNIZATION; COLOSTRUM AB Purpose. To assess the relationship between breast-feeding and the risk of life-threatening rotavirus diarrhea among Bangladeshi infants and children younger than 24 months of age. Design. Case-control study. Setting. A rural Bangladesh community. Participants. One hundred two cases with clinically severe rotavirus diarrhea detected in a treatment center-based surveillance system during 1985 and 1986, and 2587 controls selected in three surveys of the same community during the same calendar interval. Outcomes. Cases and controls were compared for the frequency of antecedent breast-feeding patterns. Results. Compared with other feeding modes, exclusive breast-feeding of infants was associated with significant protection against severe rotavirus diarrhea (relative risk (RR) = 0.10; 95% confidence interval [CI] = 0.03, 0.34). However, during the second year of life, the risk of this outcome was higher in breast-fed than in non-breast-fed children (RR = 2.85; 95% CI = 0.37, 21.71), and no overall protection was associated with breast-feeding during the first 2 years of life (RR = 2.61; 95% CI = 0.62, 11.02). Conclusions. Although exclusive breast-feeding appeared to protect infants against severe rotavirus diarrhea, breast-feeding per se conferred no overall protection during the first 2 years of life, suggesting that breast-feeding temporarily postponed rather than prevented this outcome. While not detracting from efforts to promote breast-feeding to alleviate the burden of diarrhea due to nonrotaviral enteropathogens, our findings cast doubt on whether such efforts will impact on the problem of severe rotavirus diarrhea. C1 INT CTR DIARRHOEAL DIS RES,BANGLADESH,BANGLADESH. JOHNS HOPKINS UNIV,SCH PUBL HLTH,BALTIMORE,MD 21218. JAMES GAMBLE INST MED RES,CINCINNATI,OH. CTR DIS CONTROL,ATLANTA,GA 30333. RP CLEMENS, J (reprint author), NICHHD,RM 7B03,6100 EXECUT BLVD,BETHESDA,MD 20892, USA. RI Ali, Mohammad/E-2365-2017 OI Ali, Mohammad/0000-0003-1410-388X NR 25 TC 70 Z9 70 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 1993 VL 92 IS 5 BP 680 EP 685 PG 6 WC Pediatrics SC Pediatrics GA ME773 UT WOS:A1993ME77300006 PM 8414854 ER PT J AU ROTHMAN, RB BRADY, LS XU, H LONG, JB AF ROTHMAN, RB BRADY, LS XU, H LONG, JB TI CHRONIC INTRACEREBROVENTRICULAR INFUSION OF THE ANTIOPIOID PEPTIDE, PHE-LEU-PHE-GLN-PRO-GLN-ARG-PHE-NH2 (NPFF), DOWN-REGULATES MU-OPIOID BINDING-SITES IN RAT-BRAIN SO PEPTIDES LA English DT Article DE OPIOID MU-RECEPTORS; MORPHINE; FRMF-NH2; PHE-LEU-PHE-GLN-PRO-GLN-ARG-PHE-NH2; TOLERANCE; DEPENDENCE ID CENTRAL-NERVOUS-SYSTEM; CHRONIC NALTREXONE TREATMENT; MORPHINE-MODULATING PEPTIDE; SPINAL-CORD; MESSENGER-RNA; UP-REGULATION; DEPENDENCE; FLFQPQRFAMIDE; NEUROPEPTIDE; EXPRESSION AB Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 (NPFF), an endogenous mammalian antiopioid peptide, has been shown by other laboratories to attenuate the acute antinociceptive effects of morphine, the development of morphine tolerance, and naloxone-induced withdrawal in morphine-dependent rats. The present study determined the effect of chronic NPFF on mu opioid receptors and mRNA for the endogenous opioids dynorphin and enkephalin. Rats received ICV infusions of either saline or NPFF (5 mug/h) for 13 days via Alzet 2002 osmotic minipumps. Homogenate binding studies, which used whole brain membranes, demonstrated that NPFF decreased the B(max) of mu binding sites (labeled by [H-3][D-Ala2-MePhe4 Gly-ol5]enkephalin) from 262 +/- 12 to 192 +/- 12 fmolmg protein, and increased the K(d) from 1. 1 to 2.3 nM. Quantitative receptor autoradiography and in situ hybridization experiments were conducted with sections collected at the level of the striatum. The density of mu opioid binding sites labeled by [H-3][D-Ala2-MePhe4,Gly-ol5]enkephalin was decreased in all brain areas measured except the corpus callosum, and there was no change in dynorphin mRNA or enkephalin mRNA in the caudate, the nucleus accumbens, or the ventral pallidum. Rats chronically administered ICV morphine sulfate (20 mug/h) for 14 days developed tolerance to morphine and a low degree of dependence, as measured by naloxone-precipitated withdrawal. Chronic administration of NPFF concurrently with morphine sulfate did not significantly alter naloxone-induced withdrawal signs or the development of morphine tolerance. Viewed collectively with previous findings that chronic ICV infusion of anti-NPFF IgG upregulates mu receptors, these data provide additional evidence that the density of CNS mu receptors is tonically regulated by NPFF in the extracellular fluid. The action of NPFF to decrease mu receptors is consistent with an antiopioid role for this peptide; however, the fact that NPFF (administered into the lateral ventricle) did not appreciably alter expression of morphine tolerance and dependence contrasts with previous findings and reinforces the view that this effect is most reliably seen after third ventricle administration. C1 NIMH,LNP,BETHESDA,MD 20892. WRAIR,DEPT MED NEUROSCI,WASHINGTON,DC 20307. RP ROTHMAN, RB (reprint author), NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224, USA. NR 36 TC 36 Z9 36 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0196-9781 J9 PEPTIDES JI Peptides PD NOV-DEC PY 1993 VL 14 IS 6 BP 1271 EP 1277 DI 10.1016/0196-9781(93)90187-L PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA MJ567 UT WOS:A1993MJ56700028 PM 8134310 ER PT J AU NI, Q XU, H PARTILLA, JS DECOSTA, BR RICE, KC ROTHMAN, RB AF NI, Q XU, H PARTILLA, JS DECOSTA, BR RICE, KC ROTHMAN, RB TI SELECTIVE LABELING OF KAPPA(2) OPIOID RECEPTORS IN RAT-BRAIN BY [I-125] IOXY - INTERACTION OF OPIOID-PEPTIDES AND OTHER DRUGS WITH MULTIPLE KAPPA(2A) BINDING-SITES SO PEPTIDES LA English DT Article DE OPIOID RECEPTORS; KAPPA-OPIOID RECEPTORS; DYNORPHIN; ENDORPHINS; IOXY ID BOVINE ADRENAL-MEDULLA; FREELY MOVING RATS; GUINEA-PIG BRAIN; OPIATE RECEPTORS; AFFINITY STATES; GUANINE-NUCLEOTIDES; MEDIATED PHENOMENA; H-3 NALOXONE; ANTAGONIST; BUPRENORPHINE AB Recent studies from our laboratory resolved two subtypes of the kappa2 binding site, termed kappa2a and kappa2b, using guinea pig, rat, and human brain membranes depleted of mu and delta receptors by pretreatment with the site-directed acylating agents BIT (mu-selective) and FIT (delta-selective). 6beta-Iodo-3,14-dihydroxy-17-cyclopropylmethyl-4,5alpha-epoxymorphinan (IOXY), an opioid antagonist that has high affinity for kappa2 Sites, was radioiodinated to maximum specific activity (2200 Ci/mmol) and purified by high pressure liquid chromotography and used to characterize multiple kappa2 binding sites. The results indicated that [I-125]IOXY, like [H-3]bremazocine, selectively labels kappa2 binding sites in rat brain membranes pretreated with BIT and FIT. Using 100 nM [D-ala2-MePhe4,Gly-ol5]enkephalin to block [I-125]IOXY binding to the kappa2b site, two subtypes of the kappa2a binding site were resolved, both in the absence and presence of 50 muM 5'-guanylyimidodiphosphate. Viewed collectively, these results provide further evidence for heterogeneity of the kappa opioid receptor, which may provide new targets for drug design, synthesis, and therapeutics. C1 NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,POB 5180,BALTIMORE,MD 21224. NIDDK,MED CHEM LAB,BETHESDA,MD 20892. NR 77 TC 24 Z9 24 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0196-9781 J9 PEPTIDES JI Peptides PD NOV-DEC PY 1993 VL 14 IS 6 BP 1279 EP 1293 DI 10.1016/0196-9781(93)90188-M PG 15 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA MJ567 UT WOS:A1993MJ56700029 PM 8134311 ER PT J AU THIBAULT, A FIGG, WD COOPER, MR PRINDIVILLE, SA SARTOR, AO HEADLEE, DJ MYERS, CE AF THIBAULT, A FIGG, WD COOPER, MR PRINDIVILLE, SA SARTOR, AO HEADLEE, DJ MYERS, CE TI ANAPHYLACTOID REACTION WITH SURAMIN SO PHARMACOTHERAPY LA English DT Note AB Suramin, a drug used to treat parasitic diseases, is currently being investigated as a treatment for metastatic prostate cancer. A 73-year-old man had an anaphylactoid reaction following the first dose of suramin. It was treated successfully with epinephrine, diphenhydramine, and hydrocortisone. Investigators should be aware of the possibility of such a reaction with parenteral administration of this drug. RP FIGG, WD (reprint author), NCI,CLIN PHARMACOL BRANCH,BLDG 10,ROOM 5A01,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Figg Sr, William/M-2411-2016 NR 11 TC 6 Z9 6 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 1993 VL 13 IS 6 BP 656 EP 657 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MJ916 UT WOS:A1993MJ91600017 PM 8302692 ER PT J AU DAWSON, TM STEINER, JP DAWSON, VL DINERMAN, JL UHL, GR SNYDER, SH AF DAWSON, TM STEINER, JP DAWSON, VL DINERMAN, JL UHL, GR SNYDER, SH TI IMMUNOSUPPRESSANT FK506 ENHANCES PHOSPHORYLATION OF NITRIC-OXIDE SYNTHASE AND PROTECTS AGAINST GLUTAMATE NEUROTOXICITY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE IMMUNOPHILINS; CALCINEURIN; PROTEIN PHOSPHATASE; EXCITOTOXICITY; CYCLOSPORINE-A ID CALCINEURIN PHOSPHATASE-ACTIVITY; RAPAMYCIN-BINDING-PROTEIN; AMINO-ACID RECEPTORS; CYCLOSPORINE-A; NMDA RECEPTORS; MOLECULAR-CLONING; NERVOUS-SYSTEM; KINASE-C; IMMUNOPHILIN; INHIBITION AB Immunosuppressants FK506 and cyclosporin A inhibit neurotoxicity of N-methyl-D-aspartate in primary cortical cultures, while having no effect on quisqualate- and kainate-mediated neurotoxicity. Rapamycin completely reverses the neuroprotective effect of FK506. Both FK506 and cyclosporin A inhibit NMDA-elicited/nitric oxide-mediated increases in cGMP levels in cortical cultures. FK506 has no effect on sodium nitroprusside-induced increases in cGMP. In a stably transfected human kidney 293 cell line overexpressing the gene encoding nitric oxide synthase [L-arginine, NADPH:oxygen oxidoreductase (nitric oxide-forming), EC 1.14.13.39], FK506 inhibits the calcium ionophore A23187, stimulated increases in nitrite (a breakdown product of nitric oxide), and potentiates phorbol ester-mediated inhibition of nitrite formation. FK506-mediated inhibition of nitric oxide formation is completely reversed by rapamycin. Calcineurin dephosphorylates protein kinase C-mediated phosphorylation of nitric oxide synthase. FK506 prevents the calcineurin-mediated dephosphorylation of nitric oxide synthase and thereby diminishes the enzyme's catalytic activity. These data establish nitric oxide synthase as a calcineurin substrate. Nitric oxide synthase catalytic activity is regulated by the phosphorylation state of the enzyme. Enhanced phosphorylation of nitric oxide synthase diminishes catalytic activity, and dephosphorylation (through activation of calcineurin) enhances catalytic activity. The neuroprotective effect of FK506 and cyclosporin A presumably involves the inhibition of calcineurin, preventing the dephosphorylation of nitric oxide synthase and its subsequent activation. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,725 N WOLFE ST,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL & MOLEC SCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV CARDIOL,BALTIMORE,MD 21205. NIDA,ADDICT RES CTR,MOLEC NEUROBIOL BRANCH,BALTIMORE,MD 21224. OI Dawson, Valina/0000-0002-2915-3970 FU NIDA NIH HHS [DA-00074, DA-00266]; NINDS NIH HHS [NS-01578] NR 42 TC 487 Z9 492 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 NOV 1 PY 1993 VL 90 IS 21 BP 9808 EP 9812 DI 10.1073/pnas.90.21.9808 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MF296 UT WOS:A1993MF29600014 PM 7694293 ER PT J AU WINK, DA HANBAUER, I KRISHNA, MC DEGRAFF, W GAMSON, J MITCHELL, JB AF WINK, DA HANBAUER, I KRISHNA, MC DEGRAFF, W GAMSON, J MITCHELL, JB TI NITRIC-OXIDE PROTECTS AGAINST CELLULAR-DAMAGE AND CYTOTOXICITY FROM REACTIVE OXYGEN SPECIES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ISCHEMIA-REPERFUSION INJURY; FOCAL CEREBRAL-ISCHEMIA; GUINEA-PIG HEART; MYOCARDIAL-ISCHEMIA; GLUTAMATE NEUROTOXICITY; SUPEROXIDE-DISMUTASE; HISTAMINE-RELEASE; FENTON REACTION; NEURONAL DEATH; NERVOUS-SYSTEM AB Nitric oxide, NO, which is generated by various components of the immune system, has been presumed to be cytotoxic. However, NO has been proposed to be protective against cellular damage resulting during ischemia reperfusion. Along with NO there is often concomitant formation of superoxide/hydrogen peroxide, and hence a synergistic relationship between the cytotoxic effects of nitric oxide and these active oxygen species is frequently assumed. To study more carefully the potential synergy between NO and active oxygen species in mammalian cell cytotoxicity, we utilized either hypoxanthine/xanthine oxidase (a system that generates superoxide/hydrogen peroxide) or hydrogen peroxide itself. NO generation was accomplished by the use of a class of compounds known as ''NONOates,'' which release NO at ambient temperatures without the requirement of enzyme activation or biotransformation. When Chinese hamster lung fibroblasts (V79 cells) were exposed to hypoxanthine/xanthine oxidase for various times or increasing amounts of hydrogen peroxide, there was a dose-dependent decrease in survival of V79 cells as measured by clonogenic assays. However, in the presence of NO released from (C2H5)2N[N(O)NO]-Na+ (DEA/NO), the cytotoxicity resulting from superoxide or hydrogen peroxide was markedly abrogated. Similarly, primary cultures of rat mesencephalic dopaminergic cells exposed either to hydrogen peroxide or to hypoxanthine/xanthine oxidase resulted in the degradation of the dopamine uptake and release mechanism. As was observed in the case of the V79 cells, the presence of NO essentially abrogated this peroxide-mediated cytotoxic effect on mesencephalic cells. C1 NCI,RADIAT ONCOL BRANCH,RADIOL SECT,BLDG 10,ROOM B3-B69,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,CHEM SECT,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NHLBI,CHEM PHARMACOL LAB,BETHESDA,MD 20892. NR 40 TC 662 Z9 680 U1 4 U2 21 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 1993 VL 90 IS 21 BP 9813 EP 9817 DI 10.1073/pnas.90.21.9813 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MF296 UT WOS:A1993MF29600015 PM 8234317 ER PT J AU SLOAN, SB WEISBERG, RA AF SLOAN, SB WEISBERG, RA TI USE OF A GENE ENCODING A SUPPRESSOR TRANSFER-RNA AS A REPORTER OF TRANSCRIPTION - ANALYZING THE ACTION OF THE NUN PROTEIN OF BACTERIOPHAGE-HK022 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TRANSCRIPTION TERMINATION; RNA PROCESSING; REPORTER GENES ID ESCHERICHIA-COLI; TERMINATION FACTOR; LAMBDA; TRANSLATION; ATTENUATION; EXPRESSION; POLYMERASE; MUTATIONS; SIGNALS; INVIVO AB The Nun protein of phage HK022 blocks the expression of genes that lie downstream of the nut sites of phage lambda. Nun is believed to act by promoting premature termination of transcription at or near these sites. To test this hypothesis and to facilitate mapping the sites of termination, we inserted a gene encoding a suppressor tRNA immediately downstream of the lambda nutL site and determined the effect of Nun on tRNA level. We found that Nun severely reduced the accumulation of mature, biologically active tRNA and promoted the accumulation of short, promoter-proximal transcripts whose 3' ends were dispersed over a 100-nucleotide region downstream of nutL. These results are consistent with the hypothesis that Nun terminates transcription within the region immediately down-stream of nutL and are inconsistent with the hypothesis that the only action of Nun is to prevent translation of genes located downstream of the nut site. The stability, small size, and easily assayable biological function of suppressor tRNA recommend it as a reporter of transcription in other systems. RP SLOAN, SB (reprint author), NICHHD,MOLEC GENET LAB,BLDG 6B,ROOM 448,BETHESDA,MD 20892, USA. NR 31 TC 28 Z9 28 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 NOV 1 PY 1993 VL 90 IS 21 BP 9842 EP 9846 DI 10.1073/pnas.90.21.9842 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MF296 UT WOS:A1993MF29600021 PM 8234323 ER PT J AU GEISER, AG LETTERIO, JJ KULKARNI, AB KARLSSON, S ROBERTS, AB SPORN, MB AF GEISER, AG LETTERIO, JJ KULKARNI, AB KARLSSON, S ROBERTS, AB SPORN, MB TI TRANSFORMING GROWTH FACTOR-BETA(1) (TGF-BETA(1) CONTROLS EXPRESSION OF MAJOR HISTOCOMPATIBILITY GENES IN THE POSTNATAL MOUSE - ABERRANT HISTOCOMPATIBILITY ANTIGEN EXPRESSION IN THE PATHOGENESIS OF THE TGF-BETA(1) NULL MOUSE PHENOTYPE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; TUMOR-NECROSIS-FACTOR; MHC CLASS-I; FACTOR-BETA; CD8 EXPRESSION; T-CELLS; INTERFERON; COMPLEX; DISEASE; IMMUNE AB The phenotype of the transforming growth factor beta1 (TGF-beta1) null mouse has been previously described and is characterized by inflammatory infiltrates in multiple organs leading to a wasting syndrome and death as early as 3 weeks after birth. Since this phenotype occurs in the absence of any detectable pathogen, potential autoimmune disease mechanisms were investigated. We examined major histocompatibility complex (MHC) mRNA expression in tissues of the TGF-beta1 null mouse and found levels of both the class I and class II MHC mRNA elevated compared to normal or TGF-beta1 heterozygous littermates. This elevated expression was seen prior to any evidence of inflammatory infiltrates, suggesting a causal relationship between increased MHC expression and activation of immune cell populations. Cell surface expression of MHC molecules was detected by immunohistochemistry and correlated well with mRNA levels. Expression of mRNA for interferon gamma and its receptor was unchanged at the ages when increased MHC expression became apparent. Down-regulation of class I MHC expression by TGF-beta1 was also demonstrated in vitro in fibroblasts isolated from TGF-beta1 null mice. These findings suggest that one natural function of TGF-beta1 is to control expression of both MHC classes. Altered regulation of MHC expression may be a critical step leading to the multifocal inflammation and wasting syndrome seen in the TGF-beta1 null mouse. These results suggest potential applications for TGF-beta in the management of autoimmune disease, allograft rejection, and other problems associated with altered MHC expression. C1 NINCDS,DEV & METAB NEUROL BRANCH,BETHESDA,MD 20892. RP GEISER, AG (reprint author), NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892, USA. NR 52 TC 144 Z9 150 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 NOV 1 PY 1993 VL 90 IS 21 BP 9944 EP 9948 DI 10.1073/pnas.90.21.9944 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MF296 UT WOS:A1993MF29600042 PM 8234339 ER PT J AU SMIT, LS WILKINSON, DJ MANSOURA, MK COLLINS, FS DAWSON, DC AF SMIT, LS WILKINSON, DJ MANSOURA, MK COLLINS, FS DAWSON, DC TI FUNCTIONAL ROLES OF THE NUCLEOTIDE-BINDING FOLDS IN THE ACTIVATION OF THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CHLORIDE CHANNEL; TRAFFIC ATPASES ID BACTERIAL TRANSPORT PROTEINS; CFTR CHLORIDE CHANNEL; MULTIDRUG RESISTANCE; PERIPLASMIC PERMEASES; STRUCTURAL MODEL; ADENYLATE KINASE; XENOPUS OOCYTES; CL CHANNEL; GENE; ATP AB The cystic fibrosis transmembrane conductance regulator (CFTR), a member of the traffic ATPase superfamily, possesses two putative nucleotide-binding folds (NBFs). The NBFs are sufficiently similar that sequence alignment of highly conserved regions can be used to identify analogous residues in the two domains. To determine whether this structural homology is paralleled in function, we compared the activation of chloride conductance by forskolin and 3-isobutyl-1-methylxanthine in Xenopus oocytes expressing CFTRs bearing mutations in NBF1 or NBF2. Mutation of a conserved glycine in the putative linker domain in either NBF produced virtually identical changes in the sensitivity of chloride conductance to activating conditions, and mutation of this site in both NBFs produced additive effects, suggesting that in the two NBFs this region plays a similar and critical role in the activation process. In contrast, amino acid substitutions in the Walker A and B motifs, thought to form an integral part of the nucleotide-binding pockets, produced strikingly different effects in NBF1 and NBF2. Substitutions for the conserved lysine (Walker A) or aspartate (Walker B) in NBF1 resulted in a marked decrease in sensitivity to activation, whereas the same changes in NBF2 produced an increase in sensitivity. These results are consistent with a model for the activation of CFTR in which both NBF1 and NBF2 are required for normal function but in which either the nature or the exact consequences of nucleotide binding differ for the two domains. C1 UNIV MICHIGAN, DEPT PHYSIOL, ANN ARBOR, MI 48109 USA. UNIV MICHIGAN, BIOENGN PROGRAM, ANN ARBOR, MI 48109 USA. UNIV MICHIGAN, DEPT INTERNAL MED, ANN ARBOR, MI 48109 USA. NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. RP SMIT, LS (reprint author), UNIV MICHIGAN, DEPT HUMAN GENET, ANN ARBOR, MI 48109 USA. FU NIDDK NIH HHS [DK29786, DK39690, DK45880] NR 42 TC 85 Z9 85 U1 1 U2 2 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 NOV 1 PY 1993 VL 90 IS 21 BP 9963 EP 9967 DI 10.1073/pnas.90.21.9963 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MF296 UT WOS:A1993MF29600046 PM 7694298 ER PT J AU TUGENDREICH, S BOGUSKI, MS SELDIN, MS HIETER, P AF TUGENDREICH, S BOGUSKI, MS SELDIN, MS HIETER, P TI LINKING YEAST GENETICS TO MAMMALIAN GENOMES - IDENTIFICATION AND MAPPING OF THE HUMAN HOMOLOG OF CDC27 VIA THE EXPRESSED SEQUENCE TAG (EST) DATA-BASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ACID SUBSTITUTION MATRICES; SACCHAROMYCES-CEREVISIAE; PROTEIN BLOCKS; MUTATION; ENCODES; MITOSIS; PRODUCT; FAMILY; MOTIF; MAP AB We describe a strategy for quickly identifying and positionally mapping human homologs of yeast genes to cross-reference the biological and genetic information known about yeast genes to mammalian chromosomal maps. Optimized computer search methods have been developed to scan the rapidly expanding expressed sequence tag (EST) data base to find human open reading frames related to yeast protein sequence queries. These methods take advantage of the newly developed BLOSUM scoring matrices and the query masking function SEG. The corresponding human cDNA is then used to obtain a high-resolution map position on human and mouse chromosomes, providing the links between yeast genetic analysis and mapped mammalian loci. By using these methods, a human homolog of Saccharomyces cerevisiae CDC27 has been identified and mapped to human chromosome 17 and mouse chromosome 11 between the Pkca and Erbb-2 genes. Human CDC27 encodes an 823-aa protein with global similarity to its fungal homologs CDC27, nuc2+, and BimA. Comprehensive cross-referencing of genes and mutant phenotypes described in humans, mice, and yeast should accelerate the study of normal eukaryotic biology and human disease states. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MOLEC BIOL & GENET,BALTIMORE,MD 21205. NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT MICROBIOL,DURHAM,NC 27710. FU NCI NIH HHS [5T32CA09139, CA16519]; NHGRI NIH HHS [HG-00101] NR 27 TC 54 Z9 55 U1 5 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 1993 VL 90 IS 21 BP 10031 EP 10035 DI 10.1073/pnas.90.21.10031 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MF296 UT WOS:A1993MF29600060 PM 8234252 ER PT J AU KIBBEY, MC JUCKER, M WEEKS, BS NEVE, RL VANNOSTRAND, WE KLEINMAN, HK AF KIBBEY, MC JUCKER, M WEEKS, BS NEVE, RL VANNOSTRAND, WE KLEINMAN, HK TI BETA-AMYLOID PRECURSOR PROTEIN BINDS TO THE NEURITE-PROMOTING IKVAV SITE OF LAMININ SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ALZHEIMERS-DISEASE; A-CHAIN; SYNTHETIC PEPTIDE; BASEMENT-MEMBRANE; IDENTIFICATION; EXPRESSION; OUTGROWTH; CELLS; LOCALIZATION; SEQUENCE AB We previously characterized a 110-kDa membrane-associated laminin-binding protein (LBP110) from brain which binds the laminin A chain -Ile-Lys-Val-Ala-Val-(IKVAV) site and increases in injury. Here we demonstrate that antisera directed against different epitopes of beta-amyloid precursor protein (APP) recognize LBP110 and that APP is recognized by LBP110 antiserum. APP specifically binds IKVAV and not another biologically active laminin-derived peptide containing the amino acid sequence -Tyr-Ile-Gly-Ser-Arg-. PC-12 cells transfected with antisense APP RNA produce less APP and LBP110, and they form fewer processes when cultured on either laminin or the IKVAV peptide. Thus, LBP110 is a member of the APP family and a function for APP in neurite outgrowth is now defined. C1 SWISS FED INST TECHNOL,DEPT NEUROBIOL,CH-8093 ZURICH,SWITZERLAND. MCLEAN HOSP,MOLEC NEUROGENET LAB,BELMONT,MA 02178. UNIV CALIF IRVINE,CALIF COLL MED,DEPT MICROBIOL & MOLEC GENET,IRVINE,CA 92717. RP KIBBEY, MC (reprint author), NIDR,DEV BIOL LAB,BLDG 30,ROOM 417,BETHESDA,MD 20892, USA. FU NIA NIH HHS [AG00538]; NIDCR NIH HHS [DE05599]; NINDS NIH HHS [NS28406] NR 42 TC 152 Z9 155 U1 1 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 NOV 1 PY 1993 VL 90 IS 21 BP 10150 EP 10153 DI 10.1073/pnas.90.21.10150 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MF296 UT WOS:A1993MF29600084 PM 8234269 ER PT J AU SEDER, RA GAZZINELLI, R SHER, A PAUL, WE AF SEDER, RA GAZZINELLI, R SHER, A PAUL, WE TI INTERLEUKIN-12 ACTS DIRECTLY ON CD4+ T-CELLS TO ENHANCE PRIMING FOR INTERFERON-GAMMA PRODUCTION AND DIMINISHES INTERLEUKIN-4 INHIBITION OF SUCH PRIMING SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MONOCLONAL-ANTIBODY; STIMULATORY FACTOR; IFN-GAMMA; IL-4; INVITRO; TH1; LEISHMANIASIS; EXPRESSION; CYTOKINE; CLONING AB Naive CD4+ T cells produce interleukin 2 (IL-2) but little IL-4 or interferon gamma (IFN-gamma). In vitro, they develop into IL-4 or IFN-gamma producers depending on the conditions of the priming culture. Using T-cell receptor transgenic CD4+ T cells, the role of IL-12 and IL-4 in antigen-specific printing was examined. IL-12 substantially enhanced the ability of naive CD4+ T cells to develop into cells that produced IFN-gamma upon restimulation. However, it was not essential since anti-IL-12 antibodies failed to block the priming for IFN-gamma observed in the absence of exogenous IL-12. When both IL-12 and IL-4 were present in the priming culture, IL-12 did not inhibit priming for IL-4 production. In contrast, IL-4 diminished but did not abolish priming for IFN-gamma production. In an accessory cell-independent priming system, IL-12 strikingly augmented priming for IFN-gamma production, indicating that it acts directly on T cells. IFN-gamma itself did not enhance priming for IFN-gamma production in either accessory cell-dependent or independent systems. In an accessory cell-dependent system, the IL-12-mediated enhancement was not blocked by adding neutralizing anti-IFN-gamma monoclonal antibody. However, in an accessory cell-independent system, anti-IFN-gamma antibody did inhibit priming for IFN-gamma production leaving open a role for IFN-gamma in the priming process. These data indicate that IL-12 has a major effect on the inductive phase of T-cell priming by enhancing commitment to IFN-gamma production and thus can profoundly influence the state of immunity that develops. C1 NIAID,IMMUNOL & CELL BIOL SECT,PARASIT DIS LAB,BETHESDA,MD 20892. RP SEDER, RA (reprint author), NIAID,IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 33 TC 919 Z9 927 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 1993 VL 90 IS 21 BP 10188 EP 10192 DI 10.1073/pnas.90.21.10188 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MF296 UT WOS:A1993MF29600092 PM 7901851 ER PT J AU KEW, MC MILLER, RH CHEN, HS TENNANT, BC PURCELL, RH AF KEW, MC MILLER, RH CHEN, HS TENNANT, BC PURCELL, RH TI MUTANT WOODCHUCK HEPATITIS-VIRUS GENOMES FROM VIRIONS RESEMBLE REARRANGED HEPADNAVIRAL INTEGRANTS IN HEPATOCELLULAR-CARCINOMA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TOPOISOMERASE-I; HEPATITIS-B VIRUS ID DNA TOPOISOMERASE-II; CELLS; CLONING; SITES; RECOMBINATION; REPLICATION; CHROMOSOME; SEQUENCES; EXCISION; FORMS AB Although hepadnaviruses are implicated in the etiology of hepatocellular carcinoma, the pathogenic mechanisms involved remain uncertain. Clonally propagated integrations of hepadnaviral DNA into cellular DNA can be demonstrated in most virally induced hepatocellular carcinomas. Integration occurs at random sites in cellular DNA, but the highly preferred sites in viral DNA are adjacent to the directly repeated sequence DR1, less often DR2, or in the cohesive overlap region. Integrants invariably contain simple deletions or complex rearrangements that have been thought to occur after integration. We report here the detection of mutant woodchuck hepatitis virus (WHV) genomes cloned from virions in serum that are strikingly similar to the rearranged hepadnaviral genomes found previously as integrated sequences in cellular DNA. Of 102 cloned genomes studied, 2 had large inverted duplications, 1 a 219-nucleotide direct duplication, and 1 a 219-nucleotide deletion. Virus-virus DNA junctions occurred either adjacent to DR1 or DR2 or in the cohesive overlap region at preferred topoisomerase I cleavage sites. Since these sites are located in the single-stranded regions of the genome, cleavage by topoisomerase I would produce linear molecules that would be expected to be highly recombinogenic since this enzyme, possessing nicking and ligating activities, would remain covalently attached. Sucrose density gradient centrifugation coupled with polymerase chain reaction studies confirmed that the mutant WHV DNA forms resided in virions and did not represent free viral DNA released from infected cells or were unlikely to be an artifact of the cloning process. Thus, the finding in virions of mutant WHV DNA similar to WHV DNA integrated into cellular DNA suggests that the processes of mutation and integration are linked in some instances. Furthermore, the mutant genomes that are preferentially integrated into cellular DNA may have an etiologic role in hepatocarcinogenesis. C1 NIAID,HEPATITIS VIRUSES SECT,INFECT DIS LAB,BETHESDA,MD 20892. CORNELL UNIV,COLL VET MED,ITHACA,NY 14853. FU NIAID NIH HHS [N01 AI82698] NR 28 TC 22 Z9 21 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 1993 VL 90 IS 21 BP 10211 EP 10215 DI 10.1073/pnas.90.21.10211 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MF296 UT WOS:A1993MF29600097 PM 8234278 ER PT J AU WANG, JB IMAI, YS EPPLER, CM GREGOR, P SPIVAK, CE UHL, GR AF WANG, JB IMAI, YS EPPLER, CM GREGOR, P SPIVAK, CE UHL, GR TI MU-OPIATE RECEPTOR - CDNA CLONING AND EXPRESSION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID KAPPA-OPIOID RECEPTORS; TRANSFECTED COS CELLS; BINDING-SITES; ADENYLATE-CYCLASE; BRAIN MEMBRANES; RAT-BRAIN; DELTA; DIFFERENTIATION; MORPHINE; LIGAND AB Mu opiate receptors recognize morphine with high affinity. A 2.1-kb rat brain cDNA whose predicted translation product displays 63% identity with recently described delta and kappa opiate receptor sequences was identified through polymerase chain reaction and cDNA homology approaches. This cDNA recognizes a 10.5-kb mRNA that is expressed in thalamic neurons. COS-cell expression confers naloxonazine-, Na+-, and GTP-sensitive binding of mu but not delta or kappa opioid ligands. Expressing cells bind morphine, [D-Ala2,N-methyl-Phe4,glyol5]enkephalin (DAMGO), and [D-Ala2,D-Leu5]enkephalin (DADLE) with nanomolar or sub-nanomolar affinities, defining a mu opiate receptor that avidly recognizes analgesic and euphoric opiate drugs and opioid peptides. C1 NIDA, ADDICT RES CTR, MOLEC NEUROBIOL BRANCH, BALTIMORE, MD 21224 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROL, BALTIMORE, MD 21224 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROSCI, BALTIMORE, MD 21224 USA. AMER CYANAMID CO, DIV AGR RES, PRINCETON, NJ 08543 USA. NR 65 TC 375 Z9 384 U1 1 U2 2 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 NOV 1 PY 1993 VL 90 IS 21 BP 10230 EP 10234 DI 10.1073/pnas.90.21.10230 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MF296 UT WOS:A1993MF29600101 PM 8234282 ER PT J AU HENDERSON, RA COX, AL SAKAGUCHI, K APPELLA, E SHABANOWITZ, J HUNT, DF ENGELHARD, VH AF HENDERSON, RA COX, AL SAKAGUCHI, K APPELLA, E SHABANOWITZ, J HUNT, DF ENGELHARD, VH TI DIRECT IDENTIFICATION OF AN ENDOGENOUS PEPTIDE RECOGNIZED BY MULTIPLE HLA-A2.1-SPECIFIC CYTOTOXIC T-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CLASS-I MAJOR HISTOCOMPATIBILITY MOLECULE; XENOREACTIVITY; ALLOREACTIVITY; MASS SPECTROMETRY; ANTIGEN PROCESSING ID MAJOR HISTOCOMPATIBILITY COMPLEX; TOXIC LYMPHOCYTES-T; CLASS-I MOLECULES; MURINE CELLS; ANTIGEN PRESENTATION; MASS-SPECTROMETRY; GENE-TRANSFER; MHC; HLA-A2; EXPRESSION AB An endogenous peptide recognized by a murine T-cell clone specific for the human class I major histocompatibility complex-encoded molecule HLA-A2.1 was identified through the use of microcapillary high-performance liquid chromatography coupled with electrospray-ionization tandem mass spectrometry. The peptide was associated with HLA-A2.1 on both normal cells and the antigen-processing-mutant cell line T2. This observation demonstrates that a processing mechanism other than that involving the transporter associated with antigen processing (TAP) proteins 1 and 2 can produce peptides that can be recognized by T cells. The peptide was also recognized by four other independently derived murine HLA-A2.1-specific murine T-cell clones. This suggests that xenogeneic responses are directed at a restricted subset of major histocompatibility complex product-associated peptides. Finally, quantitation of this peptide in cell extracts using mass spectrometry showed it to be among the most dominant HLA-A2.1 associated species on human lymphoid cells. The potential relevance of this observation to models of alloreactivity will be discussed. The methodology described should be generally useful for the identification of peptide epitopes recognized by alloreactive, tumor-specific, and autoimmune T cells. C1 UNIV VIRGINIA,SCH MED,BEIRN CARTER CTR IMMUNOL RES,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,DEPT CHEM,CHARLOTTESVILLE,VA 22903. NCI,CELL BIOL LAB,BETHESDA,MD 20892. RP HENDERSON, RA (reprint author), UNIV VIRGINIA,SCH MED,DEPT MICROBIOL,CHARLOTTESVILLE,VA 22908, USA. RI Hunt, Donald/I-6936-2012 OI Hunt, Donald/0000-0003-2815-6368 FU NIAID NIH HHS [AI20963]; NIGMS NIH HHS [GM37537] NR 38 TC 120 Z9 121 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 NOV 1 PY 1993 VL 90 IS 21 BP 10275 EP 10279 DI 10.1073/pnas.90.21.10275 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MF296 UT WOS:A1993MF29600110 PM 7694286 ER PT J AU CORDELLAMIELE, E MIELE, L MUKHERJEE, AB AF CORDELLAMIELE, E MIELE, L MUKHERJEE, AB TI IDENTIFICATION OF A SPECIFIC REGION OF LOW-MOLECULAR-WEIGHT PHOSPHOLIPASES-A(2) (RESIDUES-21-40) AS A POTENTIAL TARGET FOR STRUCTURE-BASED DESIGN OF INHIBITORS OF THESE ENZYMES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PANCREATIC PHOSPHOLIPASE-A2; GENE-EXPRESSION; PROTEIN; RESOLUTION; PEPTIDES; BIOLOGY; BINDING AB We have identified a specific region of porcine pancreatic phospholipase A2 (residues 21-40) which interacts with a neutralizing antibody causing a dramatic inhibition of its enzymatic activity (K(i) in the order of 10(-8)M). The binding equilibrium of the antibody-phospholipase A2 complex is reached in <3 min at 37-degrees-C. Fab fragments are equally effective phospholipase A2 inhibitors, as are intact IgG molecules. The inhibition is virtually complete and noncompetitive with respect to phosphatidylcholine substrate. The formation of precipitating immunocomplexes is not involved in the inhibition. The region of phospholipase A2 (residues 21-40) recognized by this antibody includes a highly conserved sequence which contains several functionally important residues of both group I and group II phospholipases A2. These data suggest that amino acid residues in this region of porcine pancreatic phospholipase A2 are accessible for interaction with inhibitors such as neutralizing antibodies and that agents specifically interacting with this region may have potent phospholipase A2 inhibitory activity. Thus, this conserved region of low molecular weight, extracellular phospholipases A2 is a potential target for structure-based design of specific noncompetitive inhibitors of these enzymes. Since these extracellular phospholipases A2 are suggested to play a pathogenic role in several important human diseases, the development of such pharmacologic inhibitors is of potential clinical importance. RP CORDELLAMIELE, E (reprint author), NICHHD,HUMAN GENET BRANCH,DEV GENET SECT,BETHESDA,MD 20892, USA. NR 30 TC 8 Z9 8 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 NOV 1 PY 1993 VL 90 IS 21 BP 10290 EP 10294 DI 10.1073/pnas.90.21.10290 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MF296 UT WOS:A1993MF29600113 PM 7694288 ER PT J AU JONES, BD PATERSON, HF HALL, A FALKOW, S AF JONES, BD PATERSON, HF HALL, A FALKOW, S TI SALMONELLA-TYPHIMURIUM INDUCES MEMBRANE RUFFLING BY A GROWTH FACTOR-RECEPTOR-INDEPENDENT MECHANISM SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GTPASES; INVASION ID CULTURED ANIMAL-CELLS; EPITHELIAL-CELLS; HELA-CELLS; SECRETORY PROTEINS; BREFELDIN-A; INVASION; BINDING; CYTOSKELETON AB Invasive Salmonella typhimurium induces dramatic actin rearrangements on the membrane surface of mammalian cells as part of its entry mechanism. These changes, which are best characterized as membranous ruffles, closely resemble the membrane changes that occur when a growth factor binds to its receptor. Recently, inhibition of the function of the small GTPases rac and rho in quiescent serum-starved fibroblasts was demonstrated to abolish growth factor-mediated ruffling and stress-fiber formation, respectively. In addition, actin changes induced by the oncogene ras were also shown to be regulated by rac and rho. Because Salmonella-induced actin rearrangements resemble those caused by growth factors, we investigated whether ras, rho, or rac regulates the membrane ruffling elicited by S. typhimurium. Surprisingly, inhibition of the functions of these GTPases had no effect on the ability of invasive S. typhimurium to induce membrane ruffles on a variety of tissue culture cells including Madin-Darby canine kidney cells, Swiss 3T3 fibroblasts, and Hep-2 cells. These results led us to examine the interactions of S. typhimurium with Henle-407 intestinal cells, which lack epidermal growth factor receptor on their membrane surface. We found no difference in the ability of invasive S. typhimurium to induce membrane ruffling and to enter Henle-407 cells with or without the epidermal growth factor receptor on the membrane surface. We, therefore, conclude that invasive S. typhimurium induces membrane ruffling and its own internalization by a rac-independent, growth factor-receptor-independent signaling pathway. C1 CHESTER BEATTY LABS,INST CANC RES,LONDON SW3 6JB,ENGLAND. NIAID,ROCKY MT LABS,HAMILTON,MT 59840. RP JONES, BD (reprint author), STANFORD UNIV,MED CTR,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305, USA. FU NIAID NIH HHS [AI26195, AI08404]; NIDDK NIH HHS [DK38707] NR 26 TC 92 Z9 93 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 NOV 1 PY 1993 VL 90 IS 21 BP 10390 EP 10394 DI 10.1073/pnas.90.21.10390 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MF296 UT WOS:A1993MF29600133 PM 8234304 ER PT J AU GALA, RR SHEVACH, EM AF GALA, RR SHEVACH, EM TI INFLUENCE OF PROLACTIN AND GROWTH-HORMONE ON THE ACTIVATION OF DWARF MOUSE LYMPHOCYTES IN-VIVO SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID NEUROENDOCRINE HORMONES; CONCANAVALIN-A; MICE; SNELL; PITUITARY; EXPRESSION; INDUCTION; RECEPTOR; INVIVO AB The influence of recombinant bovine prolactin (PRL) and recombinant bovine growth hormone (GH) was examined on the popliteal lymph node (PLN) expression of interleukin-2 receptors (IL-2R) in female Snell dwarf mice and normal litter mates after concanavalin A footpad injection. The absolute number of PLN CD4+, CD8+, or B+ cells of dwarf mice was less than that observed for normal litter mates, but when adjusted for the difference in body weight, only the absolute number of B cells was lower in dwarf animals when compared with normal litter mates. The injection of PRL or GH did not alter the observation. The administration of recombinant bovine PRL to normal animals, but not recombinant bovine GH, increased the expression of IL-2R on unstimulated PLN CD4+ and CD8+ subsets. Hormone administration to dwarf animals, however, did not alter the expression of IL-2R on unstimulated PLN T cell subsets. PLN cells from dwarf animals were poorly activated in vivo after injection of concanavalin A and the level of IL-2R expression induced was only 50% of that seen in the PLN of normal animals. The administration of PRL and GH completely corrected the defective induction of IL-2R expression on PLN from dwarf animals after concanavalin A stimulation. These findings strongly suggest that PRL and/or GH play an important role at some stage of the T cell activation process in vivo. Further studies are needed to precisely identify the defect in the dwarf mice. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RP GALA, RR (reprint author), WAYNE STATE UNIV,SCH MED,DEPT PHYSIOL,540 E CANFIELD,DETROIT,MI 48201, USA. FU NCI NIH HHS [IPA CAN 2-8325806] NR 29 TC 44 Z9 45 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD NOV PY 1993 VL 204 IS 2 BP 224 EP 230 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PC072 UT WOS:A1993PC07200014 PM 8415780 ER PT J AU STEIN, MB CLARK, M DELANEY, SM AF STEIN, MB CLARK, M DELANEY, SM TI CHRONIC CHANGES IN THYROID-HORMONES DO NOT AFFECT BRAIN ADENOSINE RECEPTORS SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE ADENOSINE RECEPTORS; GUANINE NUCLEOTIDE REGULATORY PROTEINS; HYPERTHYROIDISM; HYPOTHYROIDISM; THYROID HORMONES ID BETA-ADRENERGIC RECEPTORS; ADENYLATE-CYCLASE SYSTEM; RAT-BRAIN; G-PROTEINS; ADENOSINE-A1-RECEPTORS; BINDING; AGONIST; STATE AB 1. In this study, the authors examined the effects of chronic (14 days) changes in thyroid function on a major neuromodulatory receptor system in the brain - the adenosinergic system. While previous investigators have examined the effects of alteration in thyroid function on adenosine receptors in peripheral tissues (adipocytes), this is the first study to examine such effects in brain. 2. Three groups of male Sprague-Dawley rats were treated for 14 days with either a) oral PTU (0.00625%), iodine-free diet, and i.p. saline injections, b) i.p. saline injections, or c) i.p. triiodothyronine (25 mug/100 g) injections. 3. These manipulations reliably resulted in the production of hypothyroidism (TSH 30.2 +/- 8.6 ng/ml), euthyroidism (TSH 2.1 +/- 0.9), and hyperthyroidism (TSH <0.4). 4. Treatment had no significant effect on the B(max) or K(d) Of [H-3]DPCPX (A1-antagonist) binding to homogenates from cerebral cortex, cerebellum or hippocampus; similarly, no effect on [H-3]CGS-21680 (A2-agonist) binding to striatal homogenates was noted. 5. Similarly, quantitative autoradiographic studies failed to reveal consistent regional alterations unique to either hypo- or hyperthyroidism. 6. Incubation of sections with GppNHp resulted in the expected reduction (almost-equal-to 40%) in agonist binding, but there was no differential effect seen for either the hypo-or hyperthyrold tissues. 7. These preliminary findings suggest that alterations in brain adenosine receptors or G-protein-receptor coupling are unlikely to be requisite correlates of abnormal thyroid hormone levels. C1 UNIV MANITOBA,DEPT PSYCHIAT,WINNIPEG R3T 2N2,MANITOBA,CANADA. UNIV MANITOBA,DEPT PHARMACOL,WINNIPEG R3T 2N2,MANITOBA,CANADA. NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 19 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD NOV PY 1993 VL 17 IS 6 BP 1037 EP 1047 DI 10.1016/0278-5846(93)90029-R PG 11 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA MF006 UT WOS:A1993MF00600014 PM 8278597 ER PT J AU WHITLOW, M BELL, BA FENG, SL FILPULA, D HARDMAN, KD HUBERT, SL ROLLENCE, ML WOOD, JF SCHOTT, ME MILENIC, DE YOKOTA, T SCHLOM, J AF WHITLOW, M BELL, BA FENG, SL FILPULA, D HARDMAN, KD HUBERT, SL ROLLENCE, ML WOOD, JF SCHOTT, ME MILENIC, DE YOKOTA, T SCHLOM, J TI AN IMPROVED LINKER FOR SINGLE-CHAIN FV WITH REDUCED AGGREGATION AND ENHANCED PROTEOLYTIC STABILITY SO PROTEIN ENGINEERING LA English DT Article DE AGGREGATION; IN-VIVO TUMOR TARGETING; LINKER DESIGN; PROTEOLYTIC STABILITY; SINGLE-CHAIN FV ID ESCHERICHIA-COLI; MONOCLONAL-ANTIBODY; PROTEIN; ANTIGEN; CELLS; MOLECULES; AFFINITY; SEQUENCE; FRAGMENT AB The effects of linker length on binding affinity and degree of aggregation have been examined in the antifluorescein 4-4-20 and anticarcinoma CC49 single-chain Fvs. Longer linkers in the antifluorescein sFvs have higher affinities for fluorescein and aggregate less. A proteolytically susceptible site between Lys8 and Ser9, in the previously reported 212 linker has been identified. A new linker sequence, 218 (GSTSGSGKPGSGEGSTKG) was designed in which a proline was placed at the C-terminal side of the proteolytic clip site in the 212 linker. The CC49 sFv containing the 218 linker showed reduced aggregation and was found to be more stable to proteolysis in vitro, when compared to the CC49/212 sFv. The CC49 sFv with the longer 218 linker had higher affinity than CC49/212 sFv. An aggregated CC49/212 sFv sample had higher affinity than CC49/218 sFv. The CC49/218 and CC49/212 sFvs had similar blood clearances in mice, while the aggregated CC49/212 sFv remained in circulation significantly longer. In mice bearing LS-174T human colon carcinoma xenografts, the CC49/218 sFv showed higher tumor uptake than the CC49/212 sFv and lower tumor uptake than the aggregated CC49/212 sFv. The higher tumor uptake of the CC49/218 is most likely a result of its higher resistance to proteolysis. The higher affinity and higher tumor uptake of the aggregated CC49/212 sFv are most likely due to the repetitive nature of the TAG-72 antigen and the higher avidity of multivalent aggregates. When the sFvs were radiolabeled with a lutetium-chelate the CC49/218 sFv showed a lower accumulation in the liver and spleen compared to the aggregated CC49/212 sFv. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. RP WHITLOW, M (reprint author), ENZON INC,DEPT PROTEIN ENGN,40 KINGSBRIDGE RD,PISCATAWAY,NJ 08854, USA. NR 29 TC 186 Z9 191 U1 0 U2 12 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 1993 VL 6 IS 8 BP 989 EP 995 DI 10.1093/protein/6.8.989 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA MJ452 UT WOS:A1993MJ45200024 PM 8309948 ER PT J AU GUILLET, V LAPTHORN, A FOURNIAT, J BENOIT, JP HARTLEY, RW MAUGUEN, Y AF GUILLET, V LAPTHORN, A FOURNIAT, J BENOIT, JP HARTLEY, RW MAUGUEN, Y TI CRYSTALLIZATION AND PRELIMINARY-X-RAY INVESTIGATION OF BARSTAR, THE INTRACELLULAR INHIBITOR OF BARNASE SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE CRYSTALLIZATION; RIBONUCLEASE; INHIBITOR; AMYLOLIQUEFACIENS; PROTEIN PROTEIN COMPLEX ID RIBONUCLEASES; RESOLUTION; HOMOLOGY; PROTEINS; CRYSTAL; FAMILY AB Crystals of barstar, the intracellular inhibitor of the extracellular ribonuclease produced by Bacillus amyloliquefaciens (barnase), were obtained through vapor phase equilibration using the hanging drop technique. Three crystal forms have been characterized. Forms I and II, crystallized either in potassium phosphate or sodium citrate, are tetragonal; they exhibit a superstructure along the c-axis. Form III crystals, suitable for a high resolution structure determination, were grown from 55-65% ammonium sulfate. This crystal form is hexagonal and diffracts to at least 2 angstrom resolution at a synchrotron radiation source. It belongs to the hexagonal space group P6, with unit cell dimensions a = b = 143.6 angstrom, c = 35.6 angstrom. There are four molecules of barstar in the asymmetric unit. X-ray data have been collected to 2.2 angstrom Bragg spacing. The structure determination is underway in order to analyze conformational changes of barstar upon complexation with barnase. (C) 1993 Wiley-Liss, Inc. C1 CTR ETUD PHARMACEUT,PHYS LAB,CNRS,UPR 180,F-92296 CHATENAY MALABRY,FRANCE. CTR ETUD PHARMACEUT,MICROBIOL LAB,F-92296 CHATENAY MALABRY,FRANCE. NIDDKD,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20897. RI Guillet, Valerie/C-6058-2011; Benoit, Jean-Pierre/K-4387-2015 NR 14 TC 12 Z9 12 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-3585 J9 PROTEINS JI Proteins PD NOV PY 1993 VL 17 IS 3 BP 325 EP 328 DI 10.1002/prot.340170309 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ME996 UT WOS:A1993ME99600008 PM 8272429 ER PT J AU OZAKI, N ROSENTHAL, NE MOUL, DE SCHWARTZ, PJ OREN, DA AF OZAKI, N ROSENTHAL, NE MOUL, DE SCHWARTZ, PJ OREN, DA TI EFFECTS OF PHOTOTHERAPY WINTER SEASONAL AFFECTIVE-DISORDER ON ELECTROOCULOGRAPHIC RATIO IN WINTER SEASONAL AFFECTIVE-DISORDER SO PSYCHIATRY RESEARCH LA English DT Article DE LIGHT THERAPY; DEPRESSION; RETINA; DOPAMINE; SEROTONIN ID LIGHT-PEAK; EYE; DOPAMINE; ORIGIN; 5-HYDROXYTRYPTAMINE; SENSITIVITY; DEPRESSION AB Low electrooculographic (EGG) ratios have been reported in patients with seasonal affective disorder (SAD). This study was-undertaken to replicate these results and to consider the effects of light therapy on the EOG in SAD patients. Sixteen outpatients with SAD and 16 age-, sex-, and medication-matched control subjects had EOG testing before and after 1 week of light therapy during the winter. The EOG ratios in the SAD patients were only marginally lower than those in the normal control subjects. These differences persisted after light therapy. Although the slightly decreased EOG ratios in SAD patients might have resulted from an artifact of test variability, drowsiness, or other confounding factors, the difference between patients and control subjects raises the possibility of retinal abnormality in SAD. C1 NIMH,ENVIRONM PSYCHIAT SECT,BETHESDA,MD. RP OZAKI, N (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,BLDG 10,RM 4S-239,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Ozaki, Norio/M-8908-2014 OI Ozaki, Norio/0000-0002-7360-4898 NR 33 TC 21 Z9 21 U1 1 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD NOV PY 1993 VL 49 IS 2 BP 99 EP 107 DI 10.1016/0165-1781(93)90098-2 PG 9 WC Psychiatry SC Psychiatry GA MX090 UT WOS:A1993MX09000001 PM 8153191 ER PT J AU KATZ, JL WITKIN, JM AF KATZ, JL WITKIN, JM TI BEHAVIORAL-EFFECTS OF DOPAMINERGIC AGONISTS AND ANTAGONISTS ALONE AND IN COMBINATION IN THE SQUIRREL-MONKEY SO PSYCHOPHARMACOLOGY LA English DT Article DE QUINPIROLE; SKF 38393; SCH 23390; HALOPERIDOL; SPIPERONE; SCHEDULE-CONTROLLED RESPONDING; SQUIRREL MONKEYS ID DISCRIMINATIVE STIMULUS PROPERTIES; RECEPTOR MEDIATION; D-1 ANTAGONIST; SCH-23390; D1; QUINPIROLE; BRAIN; RATS; NEUROLEPTICS; COCAINE AB The effects on schedule-controlled operant behavior of the D-2 receptor agonist, quinpirole, and the D-1 agonist, SKF 38393, were assessed alone and in combination with selective dopamine-receptor antagonists. Squirrel monkeys (Saimiri sciureus) were trained to press a response key under fixed-interval and fixed-ratio schedules of food reinforcement. The fixed-interval schedule maintained relatively low rates of responding that increased up to food presentation. The fixed-ratio schedule maintained relatively constant high rates of responding. Quinpirole increased rates and disrupted the temporal pattern of responding under the fixed-interval schedule at doses (0.1-1.0 mg/kg) that decreased rates of responding under the fixed-ratio schedule. Under the fixed-interval schedule, the D-2 antagonists, spiperone (0.003-0.006 mg/ kg) and haloperidol (0.003-0.01 mg/kg), and the D-1 antagonist, SCH 23390 (0.03 mg/kg), shifted the quinpirole dose-effect curve to the right. The maximal effects of quinpirole were decreased at the highest doses of the antagonists. However, only spiperone antagonized effects of quinpirole on the rates of responding under the fixed-ratio schedule. The D-1 agonist, SKF 38393, dose-dependently (1.0-lO.0 mg/kg) decreased rates of responding under both schedules. Those effects were not antagonized by any doses studied of either spiperone (0.003 mg/kg) or SCH 23390 (0.003-0.3 mg/kg). Rather, both antagonists enhanced the effects of SKF 38393. The present study suggests significant differences between the effects of D-1 and D-2 agonists on schedule-controlled behavior, and differences in the antagonist actions of the D-2 antagonists haloperidol and spiperone. Further, the ''selective'' dopamine D-1 agonist, SKF 38393, has behavioral effects that cannot be antagonized by either a D-1 or D-2 antagonist, suggesting that some other mechanism has a significant role in mediating its behavioral effects. RP KATZ, JL (reprint author), NIDA,ADDICT RES CTR,PSYCHOBIOL SECT,POB 5180,BALTIMORE,MD 21224, USA. OI Katz, Jonathan/0000-0002-1068-1159 NR 35 TC 15 Z9 15 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 1993 VL 113 IS 1 BP 19 EP 25 DI 10.1007/BF02244328 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA MG372 UT WOS:A1993MG37200004 PM 7862823 ER PT J AU PIVIK, RT BROUGHTON, RJ COPPOLA, R DAVIDSON, RJ FOX, N NUWER, MR AF PIVIK, RT BROUGHTON, RJ COPPOLA, R DAVIDSON, RJ FOX, N NUWER, MR TI GUIDELINES FOR THE RECORDING AND QUANTITATIVE-ANALYSIS OF ELECTROENCEPHALOGRAPHIC ACTIVITY IN RESEARCH CONTEXTS SO PSYCHOPHYSIOLOGY LA English DT Article DE EEG RECORDINGS; ARTIFACTS; SLEEP; PEDIATRICS; QUANTIFIED EEG; STATISTICAL ANALYSES ID BRAIN ELECTRICAL-ACTIVITY; SCALP CURRENT-DENSITY; CEREBRAL ASYMMETRY; EEG; ISSUES; TOPOGRAPHY; COHERENCE; STABILITY AB Developments in technologic and analytical procedures applied to the study of brain electrical activity have intensified interest in this modality as a means of examining brain function. The impact of these new developments on traditional methods of acquiring and analyzing electroencephalographic activity requires evaluation. Ultimately, the integration of the old with the new must result in an accepted standardized methodology to be used in these investigations. In this paper, basic procedures and recent developments involved in the recording and analysis of brain electrical activity are discussed and recommendations are made, with emphasis on psychophysiological applications of these procedures. C1 UNIV OTTAWA,DEPT PSYCHIAT,OTTAWA K1N 6N5,ONTARIO,CANADA. UNIV OTTAWA,DEPT MED NEUROL,OTTAWA K1N 6N5,ONTARIO,CANADA. NIMH,WASHINGTON,DC 20032. UNIV WISCONSIN,DEPT PSYCHOL,MADISON,WI 53706. UNIV MARYLAND,DEPT HUMAN DEV,COLL PK,MD 20742. UNIV CALIF LOS ANGELES,DEPT NEUROL,LOS ANGELES,CA 90024. NR 73 TC 410 Z9 416 U1 18 U2 45 PU SOC PSYCHOPHYSIOL RES PI WASHINGTON PA 1010 VERMONT AVE NW SUITE 1100, WASHINGTON, DC 20005 SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD NOV PY 1993 VL 30 IS 6 BP 547 EP 558 DI 10.1111/j.1469-8986.1993.tb02081.x PG 12 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA MC114 UT WOS:A1993MC11400001 PM 8248447 ER PT J AU ZAHN, TP KRUESI, MJP AF ZAHN, TP KRUESI, MJP TI AUTONOMIC ACTIVITY IN BOYS WITH DISRUPTIVE BEHAVIOR DISORDERS SO PSYCHOPHYSIOLOGY LA English DT Article DE DISRUPTIVE BEHAVIOR DISORDERS; ELECTRODERMAL ACTIVITY; HEART RATE; ATTENTION-DEFICIT HYPERACTIVITY DISORDER; CONDUCT DISORDER; AGGRESSION ID ANTISOCIAL-BEHAVIOR; ELECTRODERMAL ACTIVITY; HYPERKINETIC CHILDREN; PSYCHIATRIC-PATIENTS; CONDUCT PROBLEMS; HEART-RATE; ADOLESCENTS; AGGRESSION; ATTENTION; PSYCHOPATHOLOGY AB Skin conductance (SC) and heart rate (HR) were measured during rest, a series of tones, and a reaction time task in 34 boys with disruptive behavior disorder to ascertain (a) if this broadly defined group differed from control boys (n = 33) and (b) if there were differences within the spectrum related to component diagnoses or to target behaviors. Disruptive boys had higher resting HR than controls, due largely to those without a subdiagnosis of conduct disorder. Disruptive boys showed a smaller increment in SC response frequency for task instructions. They did not show a general deficit in phasic SC reactivity but habituated to signal stimuli at a faster rate than did controls. However, their SC response latencies were shorter despite slower motor reaction time. Responsivity variables were similar in boys with and without a subdiagnosis of conduct disorder. The data are not compatible with the hypothesis of low autonomic nervous system (ANS) baselines in disruptive boys but partially suggest low ANS reactivity. They generally support the validity of the disruptive behavior disorder spectrum. Correlations with measures of aggression and impulsivity suggest that individual differences within the spectrum might be more fruitfully described by behavior dimensions than by conventional subdiagnoses. C1 NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. RP ZAHN, TP (reprint author), NIMH,PSYCHOL & PSYCHOPATHOL LAB,BLDG 10,ROOM 4C110,BETHESDA,MD 20892, USA. NR 53 TC 56 Z9 57 U1 1 U2 7 PU SOC PSYCHOPHYSIOL RES PI WASHINGTON PA 1010 VERMONT AVE NW SUITE 1100, WASHINGTON, DC 20005 SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD NOV PY 1993 VL 30 IS 6 BP 605 EP 614 DI 10.1111/j.1469-8986.1993.tb02086.x PG 10 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA MC114 UT WOS:A1993MC11400006 PM 8248452 ER PT J AU WHITE, BA WEINTRAUB, JA CAPLAN, DJ HOLLISTER, MC MCKAIG, RG WATKINS, CA DOUGLASS, CW DASILVA, J AF WHITE, BA WEINTRAUB, JA CAPLAN, DJ HOLLISTER, MC MCKAIG, RG WATKINS, CA DOUGLASS, CW DASILVA, J TI TOWARD IMPROVING THE ORAL HEALTH OF AMERICANS - AN OVERVIEW OF ORAL HEALTH-STATUS, RESOURCES, AND CARE DELIVERY SO PUBLIC HEALTH REPORTS LA English DT Article ID BOTTLE TOOTH-DECAY; CARIES PREVALENCE; SOCIAL IMPACT; FACIAL-PAIN; DECLINE; DISEASE; LESIONS AB Dental and oral diseases may well be the most prevalent and preventable conditions affecting Americans. More than 50 percent of U.S. children, 96 percent of employed U.S. adults, and 99.5 percent of Americans 65 years and older have experienced dental caries (also called cavities). Millions of Americans suffer from periodontal diseases and other oral conditions, and more than 17 million Americans, including 10 million Americans 65 years or older, have lost all of their teeth. Preventive dental services are known to be effective in preventing and controlling dental diseases. Unfortunately, groups at highest risk for disease-the poor and minorities-have lower rates of using dental care than the U.S. average. Cost is the principal barrier to dental care for many Americans. Of the $38.7 billion spent for dental services in 1992, public programs, including Medicaid, paid for less than 4 percent of dental expenditures. More than 90 percent of care was paid for either out-of-pocket by dental consumers or through private dental insurance. Americans are at risk for other oral health problems as well. Oropharyngeal cancer strikes approximately 30,000 Americans each year and results in an estimated 8,000 deaths annually. Underlying medical or handicapping conditions, ranging from rare genetic diseases to more common chronic diseases, affect millions of Americans and can lead to oral health problems. Among persons with compromised immune systems, oral diseases and conditions can have a significant impact on health. Oral diseases and conditions, though nearly universal, can be prevented easily and controlled at reasonable cost. Prevention and early, regular primary dental care are the best strategies to improve the oral health and quality of life of all Americans. C1 NIDR,BETHESDA,MD 20892. UNIV N CAROLINA,CHAPEL HILL,NC. NR 54 TC 11 Z9 11 U1 1 U2 2 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 1993 VL 108 IS 6 BP 657 EP 672 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA MQ012 UT WOS:A1993MQ01200001 ER PT J AU SIMON, JA SCHREIBER, GB CRAWFORD, PB FREDERICK, MM SABRY, ZI AF SIMON, JA SCHREIBER, GB CRAWFORD, PB FREDERICK, MM SABRY, ZI TI INCOME AND RACIAL PATTERNS OF DIETARY VITAMIN-C INTAKE AMONG BLACK-AND-WHITE GIRLS SO PUBLIC HEALTH REPORTS LA English DT Article ID POPULATION; MORTALITY; FOOD AB The authors examined the influence of income and race on mean dietary vitamin C intake and the risk of dietary vitamin C intake at levels below the recommended dietary allowance (RDA). They performed a cross-sectional analysis of 2,032 black and white 9- and 10-year-old females, from a wide range of income groups, who participated in the National Heart, Lung, and Blood Institute Growth and Health Study. Mean intake of vitamin C, exclusive of vitamin supplements and determined by 3-day diet records, exceeded the RDA of 45 milligrams per day for that age group in all racial and income categories. The investigators found that annual household income was directly associated with mean dietary vitamin C intake (P < 0.0001) and that blacks had higher mean dietary vitamin C intakes than whites (P < 0.01). Among both blacks and whites, household income and risk of below-RDA vitamin C intake were inversely correlated, but this trend was statistically significant for blacks only (P < 0.05). Except for the lowest level income group (less than $10,000 per year), black girls from households with incomes less than $30,000 per year were at increased risk for below-RDA vitamin C intake (relative risk = 1.93 in the $10,000-$19,999 per year group and 1.63 in the $20,000-29,999 per year group, P < 0.05), compared with black girls in the highest income category. One-quarter of white girls overall and more than 30 percent of white girls in the lowest two income groups had below-RDA vitamin C intakes. If the findings are generalizable, they underscore the importance of public health programs to address the adequacy of dietary vitamin C intake among preadolescent black and white females. C1 UNIV CALIF SAN FRANCISCO,SCH MED,DEPT EPIDEMIOL & BIOSTAT,SAN FRANCISCO,CA 94143. WESTAT CORP,ROCKVILLE,MD. MARYLAND MED RES INST,NGHS,COORDINATING CTR,BALTIMORE,MD. UNIV CALIF BERKELEY,SCH PUBL HLTH,BERKELEY,CA 94720. NHLBI,GROWTH & HLTH STUDY,CTR CLIN,BERKELEY,CA. RP SIMON, JA (reprint author), VET AFFAIRS MED CTR,DEPT MED,DIV GEN INTERNAL MED,111A1,4150 CLEMENT ST,SAN FRANCISCO,CA 94121, USA. FU NHLBI NIH HHS [N01-HC-55023-26] NR 20 TC 8 Z9 8 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 1993 VL 108 IS 6 BP 760 EP 764 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA MQ012 UT WOS:A1993MQ01200012 PM 8265761 ER PT J AU PARSHAD, R PRICE, FM PIROLLO, KF CHANG, EH SANFORD, KK AF PARSHAD, R PRICE, FM PIROLLO, KF CHANG, EH SANFORD, KK TI CYTOGENETIC RESPONSE TO G(2)-PHASE X-IRRADIATION IN RELATION TO DNA-REPAIR AND RADIOSENSITIVITY IN A CANCER-PRONE FAMILY WITH LI-FRAUMENI SYNDROME SO RADIATION RESEARCH LA English DT Article ID CHROMATID ABERRATIONS; DAMAGE; CELLS; FIBROBLASTS; TRANSFORMATION; TRANSMISSION; LYMPHOCYTES; DEFICIENCY; KINETICS; GENE C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT PATHOL,BETHESDA,MD 20814. RP PARSHAD, R (reprint author), HOWARD UNIV,COLL MED,DEPT PATHOL,WASHINGTON,DC 20059, USA. NR 25 TC 43 Z9 43 U1 0 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD NOV PY 1993 VL 136 IS 2 BP 236 EP 240 DI 10.2307/3578616 PG 5 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA MJ761 UT WOS:A1993MJ76100010 PM 8248481 ER PT J AU BOICE, JD AF BOICE, JD TI LEUKEMIA RISK IN THOROTRAST PATIENTS SO RADIATION RESEARCH LA English DT Letter RP BOICE, JD (reprint author), NCI,DIV CANC ETIOL,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892, USA. NR 9 TC 5 Z9 5 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD NOV PY 1993 VL 136 IS 2 BP 301 EP 302 DI 10.2307/3578628 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA MJ761 UT WOS:A1993MJ76100022 PM 8248491 ER PT J AU CHOYKE, PL HAYES, WS SESTERHENN, IA AF CHOYKE, PL HAYES, WS SESTERHENN, IA TI PRIMARY EXTRAGONADAL GERM-CELL TUMORS OF THE RETROPERITONEUM - DIFFERENTIATION OF PRIMARY AND SECONDARY TUMORS SO RADIOGRAPHICS LA English DT Article DE GERM CELL NEOPLASM; NEOPLASMS, METASTASES; RETROPERITONEAL SPACE, NEOPLASMS ID TESTICULAR SEMINOMA; DIAGNOSIS; CARCINOMA; TESTIS; MASS AB Primary extragonadal germ cell tumors (EGCTs) of the retroperitoneum are rarely encountered. In most cases, they arise from remnants of the genital ridge, whereas the majority of retroperitoneal germ cell tumors are metastases from primary testicular tumors. Differentiating between these primary and secondary tumors can be difficult because gonadal germ cell tumors can regress or develop slowly. Careful examination of the testes with ultrasound (US) is crucial for this determination, but asynchronous or metachronous lesions in both the testes and retroperitoneum can occur. Symptoms are often nonspecific, and diagnosis is frequently delayed. Serum markers such as beta-human chorionic gonadotropin and alpha-fetoprotein are often helpful in the diagnosis and follow-up of these tumors. Imaging techniques such as US and computed tomography play a major role in the localization and differentiation of primary and secondary retroperitoneal EGCTs. Treatment of EGCTs usually requires a combination of surgery, irradiation, and chemotherapy. C1 NIH,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892. HENRY M JACKSON FDN,ROCKVILLE,MD. ARMED FORCES INST PATHOL,DEPT RADIOL,WASHINGTON,DC 20306. ARMED FORCES INST PATHOL,DEPT PATHOL,WASHINGTON,DC 20306. RP CHOYKE, PL (reprint author), NIH,DEPT DIAGNOST RADIOL,BLDG 10,RM IC660,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 35 TC 15 Z9 16 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD NOV PY 1993 VL 13 IS 6 BP 1365 EP 1375 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA MG623 UT WOS:A1993MG62300024 PM 8290730 ER PT J AU SASTRY, SM SPERDUTO, RD WARING, GO REMALEY, NA LYNN, MJ BLANCO, E MILLER, DN AF SASTRY, SM SPERDUTO, RD WARING, GO REMALEY, NA LYNN, MJ BLANCO, E MILLER, DN TI RADIAL KERATOTOMY DOES NOT AFFECT INTRAOCULAR-PRESSURE SO REFRACTIVE AND CORNEAL SURGERY LA English DT Article AB BACKGROUND: Recent reports have suggested that a secondary effect of radial keratotomy may be a reduction in intraocular pressure (IOP) levels. METHODS: In an effort to study the relationship of radial keratotomy to IOP, we compared the mean IOP from the baseline and follow-up visits during year after surgery of operated versus nonoperated eyes of patients enrolled in the Prospective Evaluation of Radial Keratotomy (PERK) study. To investigate if radial keratotomy had more of an effect on eyes with higher baseline IOPs, the same analysis was performed on a subset (134 patients) who had a baseline IOP of 15 mm Hg or greater, RESULTS: The average baseline IOP for both operated eyes and nonoperated eyes was 14.6 mm Hg. There was no significant difference in mean IOP between operated and nonoperated eyes across all time points (p=.18). Although mean IOP changed over time, it did not clinically differ in operated versus nonoperated eyes at any time point. These findings were similar in the analysis of eyes with higher baseline IOP (15 mm Hg or greater). CONCLUSION: We conclude that the radial keratotomy performed in the PERK study had no effect on IOP within 1 year after surgery. RP SASTRY, SM (reprint author), NEI,BIOMETRY & EPIDEMIOL PROGRAM,ROOM 6A18,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0883-0444 J9 REFRACT CORNEAL SURG PD NOV-DEC PY 1993 VL 9 IS 6 BP 459 EP 464 PG 6 WC Ophthalmology SC Ophthalmology GA MQ737 UT WOS:A1993MQ73700008 PM 8117645 ER PT J AU KASSERRA, CE JONES, DR AF KASSERRA, CE JONES, DR TI HYPEROSMOLALITY ALTERS THE VENTILATORY RESPONSE TO ACUTE HYPERCAPNIA AND HYPOXIA SO RESPIRATION PHYSIOLOGY LA English DT Article DE ACID-BASE BALANCE; BIRDS, DUCK; CHEMORECEPTORS, SUPPRESSION; CONTROL OF BREATHING; HYPEROSMOLALITY, INTRACELLULAR; OSMOTIC PRESSURE ID CAROTID-BODY; DUCKS; CELLS; CO2; PH; H+ AB Acute hyperosmolality in the Pekin duck results in an extracellular acidosis and hypercarbia without any stimulation of ventilation. The development of the extracellular acidosis is accompanied by the concurrent development of an intracellular alkalosis systemically which has been hypothesized to depress ventilation (Kasserra et al., J. Appl. Physiol., 1993). In order to investigate this apparent suppression of ventilation, the ventilatory response to various respiratory challenges (CO2, O2, K+) was studied both before (normosmotic) and after (hyperosmotic) hypertonic sucrose infusion. Increased plasma osmolality caused a significant drop in arterial pH of 0.06 +/- 0.01 units and a 4 Torr increase in Pa(CO2), yet did not stimulate any significant increase in ventilation despite a significant increase in oxygen consumption. Acute hyperosmolality increased the Pa(CO2) associated with resting ventilation, and decreased the magnitude of the ventilatory response to a given increase in Pa(CO2), compared with the response to the same ventilatory challenge in normosmotic animals. Acute hyperosmolality increased the ventilatory response to hypoxia and K+ compared with normosmotic animals. The opposite effect of hyperosmolality on the ventilatory responses to hypercapnia compared with hypoxia suggests that the mechanisms of chemoreception for hypercapnia and hypoxia are different. The depressed ventilatory response curve to increased Pa(CO2) and decreased arterial pH during hyperosmolality, both alone and during the hypercapnic challenge, suggests that the peripheral chemoreceptor response to pH and CO2 is suppressed. It is hypothesized that the suppression results from the intracellular alkalosis occurring during acute hyperosmolality. C1 NHLBI,BLDG 1,RMB307,BETHESDA,MD 20892. NR 26 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0034-5687 J9 RESP PHYSIOL JI Respir. Physiol. PD NOV PY 1993 VL 94 IS 2 BP 189 EP 203 DI 10.1016/0034-5687(93)90047-E PG 15 WC Physiology; Respiratory System SC Physiology; Respiratory System GA ME325 UT WOS:A1993ME32500006 PM 8272590 ER PT J AU HERSCOVITCH, P AF HERSCOVITCH, P TI EVALUATION OF THE BRAIN BY POSITRON EMISSION TOMOGRAPHY SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Review ID CEREBRAL BLOOD-FLOW; SYSTEMIC LUPUS-ERYTHEMATOSUS; GLUCOSE METABOLIC-RATE; CENTRAL NERVOUS-SYSTEM; COMPUTED-TOMOGRAPHY; OXYGEN UTILIZATION; ENERGY-METABOLISM; O-15 RADIOTRACERS; LUMPED CONSTANT; STROKE PATIENTS RP HERSCOVITCH, P (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,PET IMAGING SECT,BLDG 10,BETHESDA,MD 20892, USA. NR 137 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD NOV PY 1993 VL 19 IS 4 BP 765 EP 794 PG 30 WC Rheumatology SC Rheumatology GA MF867 UT WOS:A1993MF86700002 PM 8265822 ER PT J AU BREY, RL GHARAVI, AE LOCKSHIN, MD AF BREY, RL GHARAVI, AE LOCKSHIN, MD TI NEUROLOGIC COMPLICATIONS OF ANTIPHOSPHOLIPID ANTIBODIES SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Review ID SYSTEMIC LUPUS-ERYTHEMATOSUS; ANTI-CARDIOLIPIN ANTIBODIES; HEALTHY ELDERLY POPULATION; TRANSIENT GLOBAL AMNESIA; OCULAR VASCULAR-DISEASE; GUILLAIN-BARRE-SYNDROME; ANTICARDIOLIPIN ANTIBODIES; PROTEIN-C; CEREBRAL-ISCHEMIA; ANTICOAGULANT ACTIVITY C1 LOUISIANA STATE UNIV,MED CTR,DEPT MED,DIV RHEUMATOL,1542 TULANE AVE,NEW ORLEANS,LA 70112. UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV NEUROL,SAN ANTONIO,TX 78284. NIAMSD,BETHESDA,MD. NR 131 TC 61 Z9 63 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD NOV PY 1993 VL 19 IS 4 BP 833 EP 850 PG 18 WC Rheumatology SC Rheumatology GA MF867 UT WOS:A1993MF86700005 PM 8265825 ER PT J AU BERGASA, NV JONES, EA AF BERGASA, NV JONES, EA TI THE PRURITUS OF CHOLESTASIS SO SEMINARS IN LIVER DISEASE LA English DT Review ID PRIMARY BILIARY-CIRRHOSIS; UNILATERAL NEUROGENIC PRURITUS; BILE-ACID METABOLISM; LIVER-DISEASE; INTRAHEPATIC CHOLESTASIS; EPIDURAL MORPHINE; OPIOID ANTAGONIST; RELIEVE PRURITUS; PLASMA PERFUSION; CONTROLLED TRIAL C1 NIDDKD,DIGEST DIS BRANCH,LIVER DIS SECT,BETHESDA,MD 20892. NR 98 TC 29 Z9 29 U1 1 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0272-8087 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PD NOV PY 1993 VL 13 IS 4 BP 319 EP 327 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA MM667 UT WOS:A1993MM66700002 PM 8303314 ER PT J AU SLOAND, E KUMAR, PN PIERCE, PF AF SLOAND, E KUMAR, PN PIERCE, PF TI CHEMOTHERAPY FOR PATIENTS WITH PULMONARY KAPOSIS-SARCOMA - BENEFIT OF FILGRASTIM (G-CSF) IN SUPPORTING DOSE ADMINISTRATION SO SOUTHERN MEDICAL JOURNAL LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; IMMUNE-DEFICIENCY SYNDROME; INTERFERON-ALPHA; SYNDROME AIDS; THERAPY; MANIFESTATIONS; ZIDOVUDINE; INFECTION; TRIAL; LUNG AB Kaposi's sarcoma (KS) is common in individuals infected with the human immunodeficiency virus (HIV-1). Although KS is frequently indolent, it can also be aggressive and life-threatening, especially in patients with pulmonary involvement (PKS), who have poor survival rates when untreated. In an effort to develop treatment regimens for PKS that would prolong life or reduce clinical symptoms, we used combination chemotherapy to treat 18 patients who had AIDS and PKS; 13 (72%) of them had a history of previous opportunistic infections. Doxorubicin, bleomycin, vinblastine, vincristine, actinomycin D, and dacarbazine were used in 3-week cycles with concomitant zidovudine, zalcitabine (dideoxycytidine), or didanocine (dideoxyinosine). Antiviral therapy was continued with chemotherapy. A partial or complete response to chemotherapy was obtained in 15 of the 18 patients (83%), as characterized by clearing of infiltrates on chest films and resolution of dyspnea and cough. Only 2 patients had opportunistic infections during treatment. Median survival was 9 months; patients who received dose reductions in less than three cycles of chemotherapy survived more than 1 year. Most deaths were related to unresponsive PKS. These results indicate that patients with symptomatic PKS can be safely and effectively treated with combination chemotherapy while receiving myelosuppressive drugs such as zidovudine. Such patients receive substantial relief from dyspnea and cough. Survival for treated patients exceeds survival for untreated historical controls. C1 GEORGETOWN UNIV,MED CTR,DEPT MED,WASHINGTON,DC 20007. RP SLOAND, E (reprint author), NHLBI,BLDG 31,ROOM 5A49,BETHESDA,MD 20892, USA. NR 25 TC 19 Z9 19 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 1993 VL 86 IS 11 BP 1219 EP 1224 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA MH676 UT WOS:A1993MH67600006 PM 7694375 ER PT J AU MALLEY, JD HORNSTEIN, J AF MALLEY, JD HORNSTEIN, J TI QUANTUM-STATISTICAL INFERENCE SO STATISTICAL SCIENCE LA English DT Article DE QUANTUM MECHANICS; HEISENBERG UNCERTAINTY; JOINT DISTRIBUTION; HILBERT SPACE; SELF-ADJOINT OPERATOR; SPECTRAL MEASURE; PROBABILITY-OPERATOR MEASURE; DECISION THEORY; BAYESIAN INFERENCE; DEFINETTI REPRESENTATION THEOREM; CRAMER-RAO INEQUALITY ID PHASE MEASUREMENT; COHERENT STATES; COMMUNICATION; INFORMATION AB The three main points of this article are: 1. Quantum mechanical data differ from conventional data: for example, joint distributions usually cannot be defined conventionally; 2. rigorous methods have been developed for analyzing such data; the methods often use quantum-consistent analogs of classical statistical procedures; 3. with these procedures, statisticians, both data-analytic and more theoretically oriented, can become active participants in many new and emerging areas of science and biotechnology. In the physical realm described by quantum mechanics, many conventional statistical and probabilistic assumptions no longer hold. Probabilistic ideas are central to quantum theory but the standard Kolmogorov axioms are not uniformly applicable. Studying such phenomena requires an altered model for sample spaces, for random variables and for inference and decision making. The appropriate decision theory has been in development since the mid-1960s. It is both mathematically and statistically rigorous and conforms to the requirements of the known physical results. This article provides a tour of the structure and current applications of quantum-consistent statistical inference and decision theory. It presents examples, outlines the theory and considers applications and open problems. Certain central concepts of quantum theory are more clearly apprehended in terms of the quantum-consistent statistical decision theory. For example, the Heisenberg uncertainty principle can be obtained as a consequence of the quantum version of the Cramer-Rao inequality. This places concepts of statistical estimation and decision theory, and thus the statistician, at the center of the quantum measurement process. Quantum statistical inference offers considerable scope for participation by the statistical community, in both applications and foundational questions. C1 USN, RES LAB, REMOTE SENSING PHYS BRANCH, WASHINGTON, DC 20375 USA. RP NIH, DIV COMP RES & TECHNOL, DISTRIBUTED SYST BRANCH, BLDG 12A, ROOM 3053, BETHESDA, MD 20892 USA. NR 75 TC 27 Z9 27 U1 1 U2 4 PU INST MATHEMATICAL STATISTICS PI CLEVELAND PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA SN 0883-4237 J9 STAT SCI JI Stat. Sci. PD NOV PY 1993 VL 8 IS 4 BP 433 EP 457 DI 10.1214/ss/1177010787 PG 25 WC Statistics & Probability SC Mathematics GA MM367 UT WOS:A1993MM36700015 ER PT J AU SUTHERLAND, CM CHMIEL, JS HAIK, BG HENSON, DE WINCHESTER, DP AF SUTHERLAND, CM CHMIEL, JS HAIK, BG HENSON, DE WINCHESTER, DP TI PATIENT CHARACTERISTICS, METHODS OF EVALUATION AND TREATMENT OF OCULAR MELANOMA IN THE UNITED-STATES FOR THE YEARS 1981 AND 1987 SO SURGERY GYNECOLOGY & OBSTETRICS LA English DT Article ID UVEAL MELANOMA AB 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 resulting outcome. A previous report on malignant melanoma of the skin has been published. This report details the findings of 245 ocular melanomas in 1981 and 275 ocular melanomas in 1987. Most of the ocular melanomas were uveal. The patients with ocular melanoma were older than the patients with skin melanoma. No significant difference was found in the number of ocular instances by gender and by study year. A high percentage of non-Hispanic Caucasians were documented with this disease, and a high percentage of ocular melanomas were not classified by the standard Callender classification. A significant number of melanomas had pigmentation, and a significant number of patients had imaging studies that, in the absence of an elevated alkaline phosphatase, usually yielded negative results. Most patients were treated with enucleation, with an increase in frequency of radiation therapy from 1981 to 1987. Local and regional recurrence was not a problem, but systemic metastases occurred frequently. Type of histologic factors by the Callender classification had an influence on survival. C1 TULANE UNIV,SCH MED,DEPT OPHTHALMOL,NEW ORLEANS,LA 70112. AMER COLL SURGEONS,CHICAGO,IL 60611. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. NORTHWESTERN UNIV,SCH MED,DEPT MED PHYSIOL,CHICAGO,IL 60611. RP SUTHERLAND, CM (reprint author), TULANE UNIV,SCH MED,DEPT SURG,1430 TULANE AVE,NEW ORLEANS,LA 70112, USA. NR 9 TC 11 Z9 11 U1 0 U2 0 PU FRANKLIN H MARTIN FOUNDATION PI CHICAGO PA 55 E ERIE ST, CHICAGO, IL 60611 SN 0039-6087 J9 SURG GYNECOL OBSTET JI Surg. Gynecol. Obstet. PD NOV PY 1993 VL 177 IS 5 BP 497 EP 503 PG 7 WC Obstetrics & Gynecology; Surgery SC Obstetrics & Gynecology; Surgery GA MF153 UT WOS:A1993MF15300010 PM 8211602 ER PT J AU DANIEL, LN MAO, Y VALLYATHAN, V SAFFIOTTI, U AF DANIEL, LN MAO, Y VALLYATHAN, V SAFFIOTTI, U TI BINDING OF THE CATIONIC DYE, JANUS GREEN B, AS A MEASURE OF THE SPECIFIC SURFACE-AREA OF CRYSTALLINE SILICA IN AQUEOUS SUSPENSION SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID INDUCED PULMONARY INFLAMMATION; POLYVINYLPYRIDINE-N-OXIDE; ALVEOLAR MACROPHAGES; LUNG; QUARTZ; DUST; EXPOSURE; FIBROSIS; MOUSE C1 NIOSH,DIV RESP DIS STUDIES,LAB INVEST BRANCH,MORGANTOWN,WV 26505. RP DANIEL, LN (reprint author), NCI,EXPTL PATHOL LAB,BETHESDA,MD 20892, USA. NR 33 TC 12 Z9 12 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV PY 1993 VL 123 IS 1 BP 62 EP 67 DI 10.1006/taap.1993.1221 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA MF919 UT WOS:A1993MF91900008 PM 8236262 ER PT J AU KODAVANTI, PRS SHIN, DS TILSON, HA HARRY, GJ AF KODAVANTI, PRS SHIN, DS TILSON, HA HARRY, GJ TI COMPARATIVE EFFECTS OF 2 POLYCHLORINATED BIPHENYL CONGENERS ON CALCIUM HOMEOSTASIS IN RAT CEREBELLAR GRANULE CELLS SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID NEUROTOXICITY; BRAIN; SYNAPTOSOMES; CULTURE; CA-2+; MICE; CA2+; HEPATOCYTES; CALMODULIN; INDICATORS C1 NIEHS,DIV INTRAMURAL RES,RES TRIANGLE PK,NC 27709. RP KODAVANTI, PRS (reprint author), US EPA,HLTH EFFECTS RES LAB,DIV NEUROTOXICOL,CELLULAR & MOLEC TOXICOL BRANCH,RES TRIANGLE PK,NC 27711, USA. NR 57 TC 141 Z9 143 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV PY 1993 VL 123 IS 1 BP 97 EP 106 DI 10.1006/taap.1993.1226 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA MF919 UT WOS:A1993MF91900013 PM 8236268 ER PT J AU FARIS, R RAMZY, RMR GAD, AM WEIL, GJ BUCK, AA AF FARIS, R RAMZY, RMR GAD, AM WEIL, GJ BUCK, AA TI COMMUNITY DIAGNOSIS OF BANCROFTIAN FILARIASIS SO TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID PARASITE ANTIGENEMIA AB The objective of this study was to find the best tests for efficiently estimating the true prevalence of Bancroftian filariasis in endemic areas. The study population comprised 427 people over 10 years of age in an endemic village in Egypt. Four tests were evaluated; a standardized clinical examination, night blood examinations for microfilariae (50 muL thick films and 1 mL membrane filtration), and a test for circulating filarial antigen. 191 subjects (44.75%) had at least one positive test and were considered to have filariasis. The sensitivities of clinical examination, thick films, membrane filtration and antigen testing for filariasis were 16%, 50%, 64%, and 88%, respectively. Relative to membrane filtration of night blood, the filarial antigen test had a sensitivity of 97.5%, a positive predictive power of 71%, and a negative predictive power of 99%. None of the blood tests was a sensitive indicator of clinical filariasis; 69% of clinical cases were negative in all 3 blood tests and would have been missed if clinical examinations had not been done. Therefore, we recommend a combination of clinical examination and the filarial antigen test (with optional examination for microfilariae of those with positive antigen tests) for community diagnosis of Bancroftian filariasis in endemic areas. C1 AIN SHAMS UNIV,CTR RES & TRAINING VECTORS DIS,CAIRO,EGYPT. NIAID,BETHESDA,MD 20892. FU NIAID NIH HHS [N0I-AI-22667, AI-22488] NR 9 TC 27 Z9 27 U1 0 U2 0 PU ROYAL SOC TROPICAL MEDICINE PI LONDON PA MANSON HOUSE 26 PORTLAND PLACE, LONDON, ENGLAND W1N 4EY SN 0035-9203 J9 T ROY SOC TROP MED H JI Trans. Roy. Soc. Trop. Med. Hyg. PD NOV-DEC PY 1993 VL 87 IS 6 BP 659 EP 661 DI 10.1016/0035-9203(93)90277-W PG 3 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA ML821 UT WOS:A1993ML82100018 PM 8296366 ER PT J AU HENGEN, PN AF HENGEN, PN TI METHODS AND REAGENTS SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article RP HENGEN, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD NOV PY 1993 VL 18 IS 11 BP 446 EP 448 DI 10.1016/0968-0004(93)90147-F PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MF826 UT WOS:A1993MF82600017 PM 8291092 ER PT J AU HUERTA, MF KOSLOW, SH LESHNER, AI AF HUERTA, MF KOSLOW, SH LESHNER, AI TI THE HUMAN BRAIN PROJECT - AN INTERNATIONAL RESOURCE SO TRENDS IN NEUROSCIENCES LA English DT Article AB As the amount of basic neuroscientific information increases dramatically, its day-to-day integration and application becomes an increasing difficulty. Technological advances, particularly in computer and information sciences, should allow this information 'explosion' to become more manageable. To this end, the Human Brain Project, an initiative of several NIH Institutes and other United States Government agencies, is being developed to provide a computer database that will allow neuroscientists access to information at all levels of integration, horn genes to behavior. In this article Michael Huerta, Stephen Koslow and Alan Leshner outline the genesis and ideas behind the initiative and discuss its future development. C1 NIMH,DIV NEUROSCI & BEHAV SCI,ROCKVILLE,MD 20857. RP HUERTA, MF (reprint author), NIMH,5600 FISHERS LANE,ROOM 11-103,ROCKVILLE,MD 20857, USA. NR 1 TC 49 Z9 52 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD NOV PY 1993 VL 16 IS 11 BP 436 EP 438 DI 10.1016/0166-2236(93)90069-X PG 3 WC Neurosciences SC Neurosciences & Neurology GA MF008 UT WOS:A1993MF00800004 PM 7507612 ER PT J AU LEAPMAN, RD BRINK, J CHIU, W AF LEAPMAN, RD BRINK, J CHIU, W TI LOW-DOSE THICKNESS MEASUREMENT OF GLUCOSE-EMBEDDED PROTEIN CRYSTALS BY ELECTRON-ENERGY-LOSS SPECTROSCOPY AND STEM DARK-FIELD IMAGING SO ULTRAMICROSCOPY LA English DT Article ID COMPLEX THIN CRYSTAL; MICROSCOPY; RESOLUTION; MODES AB Electron energy loss spectroscopy and dark-field imaging in a scanning transmission electron microscope were used to determine the thickness of glucose-embedded crotoxin complex crystals. The results demonstrate the feasibility of identifying protein crystals with a thickness of half a unit cell (12.8 nm) under low-dose and low-temperature conditions. The accuracy of this method is limited by the amount of surface coating of the crystal's embedding glucose used for preserving the high-resolution structure of the protein. The histogram of the crystal thickness distribution and the spread of the anticipated crystal thickness allow us to make an estimate of the uncertainty in the glucose layer thickness. This approach can be incorporated as part of the experimental procedure in the three-dimensional data collection for structure determination of protein crystals with variable thicknesses. The measurement can be done on areas approximately 200 nm in diameter so that crystals of suitable thickness can be pre-selected before the high-resolution data is recorded. Accurate determination of the crystal thickness will optimize the data collection efficiency by avoiding the collection and subsequent analysis of unmatchable data for the three-dimensional reconstruction. C1 BAYLOR COLL MED,VERNA & MARRS MCLEAN DEPT BIOCHEM,HOUSTON,TX 77030. BAYLOR COLL MED,WM KECK CTR COMPUTAT BIOL,HOUSTON,TX 77030. RP LEAPMAN, RD (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892, USA. FU NCRR NIH HHS [RR02250] NR 33 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3991 J9 ULTRAMICROSCOPY JI Ultramicroscopy PD NOV PY 1993 VL 52 IS 2 BP 157 EP 166 DI 10.1016/0304-3991(93)90186-2 PG 10 WC Microscopy SC Microscopy GA ML729 UT WOS:A1993ML72900002 PM 8291165 ER PT J AU CARTER, HB PEARSON, JD AF CARTER, HB PEARSON, JD TI PSA VELOCITY FOR THE DIAGNOSIS OF EARLY PROSTATE-CANCER - A NEW CONCEPT SO UROLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID ANTIGEN LEVELS; TUMOR VOLUME; SERUM; MEN; HYPERPLASIA; DISEASE C1 JAMES BUCHANAN BRADY UROL INST,DEPT UROL,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,DEPT UROL,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP CARTER, HB (reprint author), JOHNS HOPKINS UNIV HOSP,DEPT UROL,403 MARBURG,600 N WOLFE ST,BALTIMORE,MD 21287, USA. NR 13 TC 69 Z9 70 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0094-0143 J9 UROL CLIN N AM JI Urol. Clin. N. Am. PD NOV PY 1993 VL 20 IS 4 BP 665 EP 670 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA MF167 UT WOS:A1993MF16700012 PM 7505974 ER PT J AU CROWE, JE COLLINS, PL LONDON, WT CHANOCK, RM MURPHY, BR AF CROWE, JE COLLINS, PL LONDON, WT CHANOCK, RM MURPHY, BR TI A COMPARISON IN CHIMPANZEES OF THE IMMUNOGENICITY AND EFFICACY OF LIVE ATTENUATED RESPIRATORY SYNCYTIAL VIRUS (RSV) TEMPERATURE-SENSITIVE MUTANT VACCINES AND VACCINIA VIRUS RECOMBINANTS THAT EXPRESS THE SURFACE GLYCOPROTEINS OF RSV SO VACCINE LA English DT Article DE RESPIRATORY SYNCYTIAL VIRUS; TEMPERATURE-SENSITIVE MUTANT; CHIMPANZEE ID COTTON RATS; PULMONARY HISTOPATHOLOGY; F-GLYCOPROTEIN; IMMUNIZATION; CHILDREN; INFECTION; INFANTS; PURIFICATION; PHENOTYPE; IMMUNITY AB Respiratory syncytial virus (RSV) is the most common cause of viral bronchiolitis and pneumonia in children. The present study compares the level of attenuation, genetic stability and efficacy of three conditional-lethal temperature-sensitive (ts) mutants of the RSV A2 wild-type virus, designated is-1, ts-1-NG1, and ts-4, in seronegative chimpanzees and also compares their efficacy with that of vaccinia virus recombinants that express the surface glycoproteins of RSV. Each of the ts mutants was highly attenuated in the lower respiratory tract, but still retained the capacity to induce significant rhinorrhoea. Each of the three ts mutants underwent partial reversion to a non-ts (ts+) phenotype during replication in a minority of the chimpanzees. The ts+ virus present in the upper respiratory tract of the chimpanzees did not spread to the lower respiratory tract and represented only a minority fraction of the virus present in the nasopharyngeal swab specimens. The ts mutants were highly immunogenic and provided resistance that effectively restricted RSV replication following virus challenge. In contrast, the vaccinia-RSV recombinants were less immunogenic. They protected the lungs of two of four chimpanzees challenged with RSV, but failed to protect the upper respiratory tract. The chimpanzee can serve as a model for the rapid evaluation of further attenuated live RSV vaccines. RP CROWE, JE (reprint author), NIAID,INFECT DIS LAB,RESP VIRUSES SECT,BETHESDA,MD 20892, USA. RI Crowe, James/B-5549-2009 OI Crowe, James/0000-0002-0049-1079 NR 33 TC 75 Z9 75 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD NOV PY 1993 VL 11 IS 14 BP 1395 EP 1404 DI 10.1016/0264-410X(93)90168-W PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA MH268 UT WOS:A1993MH26800006 PM 8310760 ER PT J AU WARD, JM SHELDON, W AF WARD, JM SHELDON, W TI EXPRESSION OF MONONUCLEAR PHAGOCYTE ANTIGENS IN HISTIOCYTIC SARCOMA OF MICE SO VETERINARY PATHOLOGY LA English DT Article DE HISTIOCYTIC SARCOMA; MONONUCLEAR PHAGOCYTE SYSTEM; MICE; RETICULUM CELL SARCOMA; TYPE A ID MALIGNANT HISTIOCYTOSIS; CELL; ORIGIN; LYMPHOMAS; PATHOLOGY AB Twenty cases of histiocytic sarcoma in 15 female and five male (384 to 722 days of age) hybrid F-1 (C57BL/6 x BALB/c) or F-2 (F-1 x F-1) mice were studied for expression of mononuclear phagocyte and other antigens. Histiocytic sarcomas were found most often in liver, uterus, spleen, and lung. Tissues fixed in Bouin's fluid provided preservation of antigen immunoreactivity, using avidin biotin peroxidase complex immunohistochemistry, with monoclonal and polyclonal antibodies. The mononuclear phagocyte antigens, lysozyme and Mac-2 (a galactose-specific lectin that binds IgE), were found in 60-70% of the cases. The receptor for the macrophage colony-stimulating factor (CSF-1), c-fms, was expressed in 2/20 (10%) of the cases. Mouse immunoglobulins were not found in histiocytic sarcoma cells. In uterine histiocytic sarcomas, previously reported as Schwannomas because of their histologic appearance, S-100 protein was not expressed by tumor cells, although they usually expressed Mac-2 and lysozyme. Hyaline droplets were found in the renal tubules of only 2/19 cases. Our studies provide evidence that murine histiocytic sarcoma expresses antigens (Mac-2, lysozyme, c-fms) found in cells of the mononuclear phagocyte series, in contrast to the B-cen origin of many human histiocytic tumors. C1 NATL CTR TOXICOL RES,PATHOL ASSOCIATES INC,JEFFERSON,AR. RP WARD, JM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,OFF LAB ANIM SCI,VET & TUMOR PATHOL SECT,FAIRVIEW 201,FREDERICK,MD 21701, USA. FU NCI NIH HHS [N01-CO-74102] NR 30 TC 11 Z9 11 U1 0 U2 0 PU AMER COLL VET PATHOLOGIST PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 SN 0300-9858 J9 VET PATHOL JI Vet. Pathol. PD NOV PY 1993 VL 30 IS 6 BP 560 EP 565 PG 6 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA MN540 UT WOS:A1993MN54000010 PM 8116150 ER PT J AU SALTARELLI, MJ SCHOBORG, R GDOVIN, SL CLEMENTS, JE AF SALTARELLI, MJ SCHOBORG, R GDOVIN, SL CLEMENTS, JE TI THE CAEV TAT GENE TRANS-ACTIVATES THE VIRAL LTR AND IS NECESSARY FOR EFFICIENT VIRAL REPLICATION SO VIROLOGY LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; ARTHRITIS-ENCEPHALITIS-VIRUS; COMPLETE NUCLEOTIDE-SEQUENCE; LONG TERMINAL REPEAT; VISNA VIRUS; HTLV-III; TRANSCRIPTIONAL ACTIVITY; AIDS VIRUS; ENV-GENE; LENTIVIRUSES C1 JOHNS HOPKINS UNIV,SCH MED,DIV COMPARAT MED,720 RUTLAND AVE,TRAYLOR BLDG,ROOM G-60,BALTIMORE,MD 21205. FREDERICK CANC RES & DEV CTR,DEPT HUMAN RETROVIRUS,FREDERICK,MD 21702. JOHNS HOPKINS UNIV,SCH MED,DEPT MOLEC BIOL & GENET,BALTIMORE,MD 21205. NIAID,INFECT DIS LAB,HEPATITIS SECT,BETHESDA,MD 20892. RI Schoborg, Robert/A-2055-2010 FU NIAID NIH HHS [AI27297, AI28748]; NINDS NIH HHS [NS23039] NR 43 TC 25 Z9 25 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD NOV PY 1993 VL 197 IS 1 BP 35 EP 44 DI 10.1006/viro.1993.1564 PG 10 WC Virology SC Virology GA MB621 UT WOS:A1993MB62100004 PM 8212571 ER PT J AU DAS, BK GENTSCH, JR HOSHINO, Y ISHIDA, SI NAKAGOMI, O BHAN, MK KUMAR, R GLASS, RI AF DAS, BK GENTSCH, JR HOSHINO, Y ISHIDA, SI NAKAGOMI, O BHAN, MK KUMAR, R GLASS, RI TI CHARACTERIZATION OF THE G-SEROTYPE AND GENOGROUP OF NEW-DELHI NEWBORN ROTAVIRUS STRAIN-116E SO VIROLOGY LA English DT Article ID AMINO-ACID-SEQUENCE; POLYMERASE CHAIN-REACTION; OUTER CAPSID PROTEIN-VP4; SUBGROUP-I SPECIFICITY; RNA-RNA HYBRIDIZATION; NUCLEOTIDE-SEQUENCE; ANIMAL ROTAVIRUSES; GENOMIC CHARACTERIZATION; NEONATAL INFECTIONS; BOVINE ROTAVIRUSES C1 CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,ATLANTA,GA 30333. ALL INDIA INST MED SCI,DEPT PEDIAT,DIV GASTROENTEROL & ENTER INFECT,NEW DELHI 110029,INDIA. AKITA UNIV,SCH MED,DEPT MICROBIOL,AKITA 010,JAPAN. ALL INDIA INST MED SCI,DEPT MICROBIOL,NEW DELHI 110029,INDIA. AKITA UNIV,SCH MED,DEPT LAB MED,AKITA 010,JAPAN. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. RI Kumar, Rajeev/I-2338-2016 OI Kumar, Rajeev/0000-0002-0783-1101 NR 63 TC 92 Z9 94 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 0042-6822 J9 VIROLOGY JI Virology PD NOV PY 1993 VL 197 IS 1 BP 99 EP 107 DI 10.1006/viro.1993.1570 PG 9 WC Virology SC Virology GA MB621 UT WOS:A1993MB62100010 PM 8212599 ER PT J AU HIRSCH, VM MCGANN, C DAPOLITO, G GOLDSTEIN, S OGENODOI, A BIRYAWAHO, B LAKWO, T JOHNSON, PR AF HIRSCH, VM MCGANN, C DAPOLITO, G GOLDSTEIN, S OGENODOI, A BIRYAWAHO, B LAKWO, T JOHNSON, PR TI IDENTIFICATION OF A NEW SUBGROUP OF SIVAGM IN TANTALUS MONKEYS SO VIROLOGY LA English DT Note ID SIMIAN IMMUNODEFICIENCY VIRUS; AFRICAN-GREEN MONKEYS; HIGHLY DIVERGENT; ANTIBODIES; LENTIVIRUS; DIVERSITY; SEQUENCE C1 GEORGETOWN UNIV,DIV MOLEC VIROL & IMMUNOL,ROCKVILLE,MD 20852. OHIO STATE UNIV,CHILDRENS HOSP,DEPT PEDIAT,COLUMBUS,OH 43210. UGANDA VIRUS RES INST,ENTEBBE,UGANDA. RP HIRSCH, VM (reprint author), NIAID,LID,IMMUNODEFICIENCY VIRUSES SECT,TWINBROOK II,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. RI Johnson, Philip/A-6892-2009 NR 21 TC 49 Z9 49 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 PY 1993 VL 197 IS 1 BP 426 EP 430 DI 10.1006/viro.1993.1606 PG 5 WC Virology SC Virology GA MB621 UT WOS:A1993MB62100046 PM 8212578 ER PT J AU DICKIE, P RAMSDELL, F NOTKINS, AL VENKATESAN, S AF DICKIE, P RAMSDELL, F NOTKINS, AL VENKATESAN, S TI SPONTANEOUS AND INDICIBLE EPIDERMAL HYPERPLASIA IN TRANSGENIC MICE EXPRESSING HIV-1 NEF SO VIROLOGY LA English DT Note ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; MUTATIONAL ANALYSIS; T-CELLS; TYPE-1; GENE; PROTEIN; REPLICATION; AIDS; ONCOGENE C1 NIAID,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892. NIDR,ORAL MED LAB,BETHESDA,MD 20892. RP DICKIE, P (reprint author), NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892, USA. NR 36 TC 34 Z9 34 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD NOV PY 1993 VL 197 IS 1 BP 431 EP 438 DI 10.1006/viro.1993.1607 PG 8 WC Virology SC Virology GA MB621 UT WOS:A1993MB62100047 PM 8212579 ER PT J AU MIMMS, LT MOSLEY, JW HOLLINGER, FB AACH, RD STEVENS, CE CUNNINGHAM, M VALLARI, DV BARBOSA, LH NEMO, GJ AF MIMMS, LT MOSLEY, JW HOLLINGER, FB AACH, RD STEVENS, CE CUNNINGHAM, M VALLARI, DV BARBOSA, LH NEMO, GJ TI EFFECT OF CONCURRENT ACUTE INFECTION WITH HEPATITIS-C VIRUS ON ACUTE HEPATITIS-B VIRUS-INFECTION SO BRITISH MEDICAL JOURNAL LA English DT Article ID TRANSFUSION-TRANSMITTED VIRUSES; NON-A-HEPATITIS; POSTTRANSFUSION HEPATITIS; RECIPIENTS; TRANSMISSION; ANTIBODY; DONORS; BLOOD; RISK AB Objective-To investigate the possible interference with acute hepatitis B virus infection by coinfection with hepatitis C virus. Design-Analysis of stored sera collected for transfusion transmitted viruses study in 1970s. Setting-Four major medical centres in the United States. Patients-12 recipients of blood infected with hepatitis B virus. Main outcome measures-In 1970s, presence of antibodies in hepatitis B virus and raised serum alanine aminotransferase concentration; detection of antibodies to hepatitis C virus with new enzyme linked immunoassays. Results-Five of the 12 patients were coinfected with hepatitis C virus. Hepatitis B surface antigen was first detected at day 59 in patients infected with hepatitis B virus alone and at day 97 in those coinfected with hepatitis C virus (p=0.01); median durations of antigenaemia were 83 and 21 days respectively (p=0.05), and the antigen concentration was lower in the coinfected patients. Alanine aminotransferase patterns were uniphasic when hepatitis B virus infection occurred alone (range 479-2465 IU/l) and biphasic in patients with combined acute infection (no value >380 IU/l; p=0.0025). Four coinfected recipients developed chronic hepatitis C virus infection. The fifth patient was followed for only four months. Conclusions-Acute coinfection with hepatitis C virus and hepatitis B virus inhibits hepatitis B virus infection in humans, and onset of hepatitis B may reduce the severity of hepatitis C virus infection but not frequency of chronicity. Alanine aminotransferase concentration showed a biphasic pattern in dual infection. C1 UNIV SO CALIF,DEPT MED,LOS ANGELES,CA 90032. ABBOTT LABS,ABBOTT PK,IL. BAYLOR COLL MED,HOUSTON,TX 77030. MT SINAI MED CTR,CLEVELAND,OH 44106. NEW YORK BLOOD CTR,NEW YORK,NY 10021. NHLBI,TRANSFUS MED BRANCH,BETHESDA,MD 20892. FU NHLBI NIH HHS [N01-HB-42972] NR 15 TC 89 Z9 90 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD OCT 30 PY 1993 VL 307 IS 6912 BP 1095 EP 1097 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA ME918 UT WOS:A1993ME91800013 PM 8251805 ER PT J AU CHANOCK, SJ TOLTZIS, P WILSON, C AF CHANOCK, SJ TOLTZIS, P WILSON, C TI CROSS-REACTIVITY BETWEEN STOMATOCOCCUS-MUCILAGINOSUS AND LATEX AGGLUTINATION FOR CRYPTOCOCCAL ANTIGEN SO LANCET LA English DT Letter C1 RAINBOW BABIES & CHILDRENS HOSP,CLEVELAND,OH 44106. UNIV ALABAMA,BIRMINGHAM,AL 35294. RP CHANOCK, SJ (reprint author), NCI,PEDIAT BRANCH,BETHESDA,MD 20892, USA. NR 2 TC 22 Z9 23 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 30 PY 1993 VL 342 IS 8879 BP 1119 EP 1120 DI 10.1016/0140-6736(93)92106-4 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA ME822 UT WOS:A1993ME82200057 PM 8105345 ER PT J AU BACKLUND, PS AF BACKLUND, PS TI CARBOXYL METHYLATION OF THE LOW-MOLECULAR-WEIGHT GTP-BINDING PROTEIN G25K - REGULATION OF CARBOXYL METHYLATION BY RHOGDI SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID GDP-DISSOCIATION INHIBITOR; BOVINE BRAIN CYTOSOL; MEMBRANE-BINDING; HUMAN HOMOLOG; RHOB P20; PURIFICATION; IDENTIFICATION; CLONING; GENE; GP RP BACKLUND, PS (reprint author), NIMH,GEN & COMPARAT BIOCHEM LAB,BETHESDA,MD 20892, USA. NR 23 TC 18 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 29 PY 1993 VL 196 IS 2 BP 534 EP 542 DI 10.1006/bbrc.1993.2283 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MG114 UT WOS:A1993MG11400006 PM 8240325 ER PT J AU HOLLIDAY, LS BUBB, MR KORN, ED AF HOLLIDAY, LS BUBB, MR KORN, ED TI RABBIT SKELETAL-MUSCLE ACTIN BEHAVES DIFFERENTLY THAN ACANTHAMOEBA ACTIN WHEN ADDED TO SOLUBE EXTRACTS OF ACANTHAMOEBA-CASTELLANII SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID POLYMERIZATION; PROTEINS; MYOSIN RP HOLLIDAY, LS (reprint author), NHLBI,CELL BIOL LAB,BETHESDA,MD 20892, USA. RI Korn, Edward/F-9929-2012 NR 10 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 29 PY 1993 VL 196 IS 2 BP 569 EP 575 DI 10.1006/bbrc.1993.2287 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MG114 UT WOS:A1993MG11400010 PM 8240329 ER PT J AU SHAHARABANY, M RICE, NR HIZI, A AF SHAHARABANY, M RICE, NR HIZI, A TI EXPRESSION AND MUTATIONAL ANALYSIS OF THE REVERSE-TRANSCRIPTASE OF THE LENTIVIRUS EQUINE INFECTIOUS-ANEMIA VIRUS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID DNA-POLYMERASE; ESCHERICHIA-COLI; H ACTIVITIES; POL GENES; TYPE-2; RIBONUCLEASE; MUTANTS; DOMAIN C1 TEL AVIV UNIV,SACKLER SCH MED,DEPT CELL BIOL & HISTOL,IL-69978 TEL AVIV,ISRAEL. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC VIROL & CARCINOGENESIS LAB,FREDERICK,MD 21702. FU NIAID NIH HHS [AI 27035]; PHS HHS [N01-C0-74101] NR 25 TC 10 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 29 PY 1993 VL 196 IS 2 BP 914 EP 920 DI 10.1006/bbrc.1993.2336 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MG114 UT WOS:A1993MG11400059 PM 7694581 ER PT J AU MILETICH, RS COMI, G BANKIEWICZ, K PLUNKETT, R ADAMS, R DICHIRO, G KOPIN, IJ AF MILETICH, RS COMI, G BANKIEWICZ, K PLUNKETT, R ADAMS, R DICHIRO, G KOPIN, IJ TI 6-[F-18]FLUORO-L-DIHYDROXYPHENYLALANINE METABOLISM AND POSITRON EMISSION TOMOGRAPHY AFTER CATECHOL-O-METHYLTRANSFERASE INHIBITION IN NORMAL AND HEMIPARKINSONIAN MONKEYS SO BRAIN RESEARCH LA English DT Article DE FLUORODIHYDROXYPHENYLALANINE; POSITRON EMISSION TOMOGRAPHY; CATECHOLAMINE METABOLISM; CATECHOL-O-METHYLTRANSFERASE; NITECAPONE; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; HEMIPARKINSONISM ID BRAIN TRANSFER CONSTANTS; TIME UPTAKE DATA; PARKINSONS-DISEASE; L-DOPA; GRAPHICAL EVALUATION; CEREBRAL-CORTEX; HOODED RAT; 6-FLUORO-L-DOPA; OR-462; NITECAPONE AB Increased and sustained central delivery of L-dihydroxyphenylalanine (L-DOPA) is a desirable therapeutic strategy in Parkinson's disease. We investigated the effects of peripheral catechol-O-methyltransferase (COMT) inhibition, by the non-toxic drug nitecapone on the metabolism of 6-[F-18]fluoro-L-dihydroxyphenylalanine (6FD) and on its positron emission tomography (PET) imaging in non-human primates. Nitecapone produced a dose-dependent inhibition in the formation of 3-O-methyl-6-[F-18]fluorodihydroxyphenylalanine (OMFD). This inhibition of OMFD formation was attended by increased production of other metabolites, in particular 6-[F-18]fluorodopamine (6FDA), 6-[F-18]fluorodihydroxyphenylacetic acid (FDOPAC), 6-[F-18]fluorohomovanillic acid (FHVA) and [F-18]-sulfated conjugates (FSC). Although nitecapone had no effect on plasma 6FD pharmacokinetics, high-dose nitecapone increased contrast of cerebral F-18 uptake and retention between regions with high (striatum) versus sparse (parieto-occipital lobes) dopaminergic innervation. F-18 uptake contrast was also improved between structures known to possess an intermediate dopaminergic innervation, including the upper brainstem, frontal and temporal lobes, versus sparsely innervated regions. This increased contrast was secondary to decreased activity in sparsely innervated structures and not to increased activity in highly innervated structures. Contrast was correlated inversely with the plasma OMFD/6FD concentration ratio, OMFD being the main 6FD metabolite which can cross the blood brain barrier. We conclude that nitecapone is an effective inhibitor of COMT in non-human primates. This inhibition results in increased 6FD flux through other catabolic pathways. Because of decreased OMFD formation, however, COMT inhibition improves the specificity of 6FD-PET and facilitates in-vivo detection of a wide range of dopaminergic innervation densities in cerebral structures. C1 NINCDS,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NIH,DEPT POSITRON EMISS TOMOG,BETHESDA,MD 20892. RP MILETICH, RS (reprint author), NINCDS,NEUROIMAGING BRANCH,9000 ROCKVILLE PIKE,BLDG 10,ROOM IC451,BETHESDA,MD 20892, USA. NR 51 TC 21 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 29 PY 1993 VL 626 IS 1-2 BP 1 EP 13 DI 10.1016/0006-8993(93)90556-3 PG 13 WC Neurosciences SC Neurosciences & Neurology GA MC801 UT WOS:A1993MC80100001 PM 8281420 ER PT J AU CHAN, KC JANINI, GM MUSCHIK, GM ISSAQ, HJ AF CHAN, KC JANINI, GM MUSCHIK, GM ISSAQ, HJ TI LASER-INDUCED FLUORESCENCE DETECTION OF 9-FLUORENYLMETHYL CHLOROFORMATE DERIVATIZED AMINO-ACIDS IN CAPILLARY ELECTROPHORESIS SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; HYDROXYPROLINE; COLLAGEN; PROLINE; SENSITIVITY; REAGENT; ASSAY AB Laser-induced fluorescence (LIF) was applied to the detection of 9-fluorenylmethyl chloroformate (FMOC-Cl) derivatized amino acids separated by capillary electrophoresis. Fluorescence excitation was provided by a pulsed, KrF laser operating at 248 nm. A limit of detection of 5.10(-10) M was obtained for FMOC-alanine (S/N = 2). Separation of FMOC-derivatized proline, hydroxyproline, and sarcosine was achieved with a 20 mM berate buffer (pH 9.2), and the separation of FMOC-derivatized amino acid standard mixture was obtained using a 20 mM berate buffer (pH 9.2) containing 25 mM sodium dodecyl sulfate. RP CHAN, KC (reprint author), NCI,FREDERICK CANC RES FACIL,PROGRAM RESOURCES INC DYNCORP,POB B,FREDERICK,MD 21701, USA. NR 26 TC 61 Z9 67 U1 0 U2 5 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 29 PY 1993 VL 653 IS 1 BP 93 EP 97 DI 10.1016/0021-9673(93)80395-O PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA MW221 UT WOS:A1993MW22100011 PM 8269054 ER PT J AU MULLER, CE SHI, D MANNING, M DALY, JW AF MULLER, CE SHI, D MANNING, M DALY, JW TI SYNTHESIS OF PARAXANTHINE ANALOGS (1,7-DISUBSTITUTED XANTHINES) AND OTHER XANTHINES UNSUBSTITUTED AT THE 3-POSITION - STRUCTURE-ACTIVITY-RELATIONSHIPS AT ADENOSINE RECEPTORS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID A2-ADENOSINE RECEPTORS; SELECTIVE ANTAGONISTS; POTENT; A1-ADENOSINE; INHIBITION; AFFINITY; PURINES; SUBSTITUTION; MEMBRANES; CAFFEINE AB Synthetic procedures for the preparation of various 3-unsubstituted xanthines, including paraxanthine analogs (1,7-disubstituted xanthines) and 1,8-disubstituted xanthines, were developed. Silylation of 1-substituted xanthines followed by alkylation at the 7-position provides a facile route to paraxanthine analogs. Regioselective alkylation of tris(trimethylsilyl)-6-aminouracil provides 3-substituted 6-aminouracils, which are converted to 1,8-disubstituted xanthines by standard procedures. The ring closure of 3-substituted 5-cyclopentanecarboxamido- and 5-(benzoylamino)-6-aminouracils requires drastic reaction conditions. Affinity for brain Al and A2 adenosine receptors was determined in binding assays for these and other xanthines with substituents in 1-, 3-, 7-, 8-, and 9-positions. Substitution at the 1-position was necessary for high affinity at adenosine receptors. 1,3-Disubstituted xanthines generally had higher affinity than 1,7-disubstituted xanthines. 1,8-Disubstituted xanthines had high affinity for adenosine receptors; some were highly selective for Al receptors. C1 PHARMAZEUT INST,MORGENSTELLE 8,D-72076 TUBINGEN,GERMANY. NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. RI Muller, Christa/C-7748-2014 OI Muller, Christa/0000-0002-0013-6624 NR 51 TC 70 Z9 70 U1 0 U2 2 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 29 PY 1993 VL 36 IS 22 BP 3341 EP 3349 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA ME931 UT WOS:A1993ME93100015 PM 8230124 ER PT J AU MOORE, JP JAMESON, BA SATTENTAU, QJ WILLEY, R SODROSKI, J AF MOORE, JP JAMESON, BA SATTENTAU, QJ WILLEY, R SODROSKI, J TI TOWARDS A STRUCTURE OF THE HIV-1 ENVELOPE GLYCOPROTEIN GP120 - AN IMMUNOCHEMICAL APPROACH SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES LA English DT Article ID VIRUS TYPE-1 GP120; T4 MOLECULE; HUMAN CD4; RECEPTOR; BINDING; RETROVIRUS; COMPONENT; FRAGMENT; ANTIGEN; DOMAINS AB The HIV-1 surface glycoprotein gp120 binds CD4 in the initial state of virus-cell fusion. The extensive glycosylation of gp120 has thus far precluded definition of its structure by crystallographic methods. As an initial approach to a gp120 structure, the surface topology was mapped using antibodies. First, the regions of gp120 that are accessible on the surface of the native molecule, and those that are internal but exposed after denaturation, are identified. Second, epitopes for antibodies that recognize complex surface strutures comprising segments of different domains are identified. Third, we define how mutations in one domain of gp120 influence the binding of antibodies to defined epitopes on other domains. These latter approaches enable us to start to understand the inter-domain interactions that contribute to the overall structure of the gp 120 molecule. Information from these studies is being used to model the structures of individual gp120 domains, and the way in which these interact in the folded protein. C1 JEFFERSON CANC INST,PHILADELPHIA,PA 19107. CTR IMMUNOL MARSEILLE LUMINY,F-13288 MARSEILLE 9,FRANCE. NIAID,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. RP MOORE, JP (reprint author), NYU,SCH MED,AARON DIAMOND AIDS RES CTR,NEW YORK,NY 10016, USA. NR 21 TC 8 Z9 8 U1 1 U2 1 PU ROYAL SOC LONDON PI LONDON PA 6 CARLTON HOUSE TERRACE, LONDON, ENGLAND SW1Y 5AG SN 0962-8436 J9 PHILOS T ROY SOC B JI Philos. Trans. R. Soc. Lond. Ser. B-Biol. Sci. PD OCT 29 PY 1993 VL 342 IS 1299 BP 83 EP 88 DI 10.1098/rstb.1993.0139 PG 6 WC Biology SC Life Sciences & Biomedicine - Other Topics GA MH277 UT WOS:A1993MH27700012 PM 7904352 ER PT J AU VAITUKAITIS, JL AF VAITUKAITIS, JL TI NCRR FUNDING MECHANISMS SO SCIENCE LA English DT Letter RP VAITUKAITIS, JL (reprint author), NCI,NATL CTR RES RESOURCES,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 29 PY 1993 VL 262 IS 5134 BP 637 EP 637 DI 10.1126/science.8235576 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MD952 UT WOS:A1993MD95200003 PM 8235576 ER PT J AU PUTNEY, JW AF PUTNEY, JW TI EXCITEMENT ABOUT CALCIUM SIGNALING IN INEXCITABLE CELLS SO SCIENCE LA English DT Article ID PC12 CELLS; RELEASE; ENTRY; MECHANISMS; STORES; GENE RP PUTNEY, JW (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 35 TC 172 Z9 174 U1 0 U2 3 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 29 PY 1993 VL 262 IS 5134 BP 676 EP 678 DI 10.1126/science.8235587 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MD952 UT WOS:A1993MD95200028 PM 8235587 ER PT J AU OTAKA, A BURKE, TR SMYTH, MS NOMIZU, M ROLLER, PP AF OTAKA, A BURKE, TR SMYTH, MS NOMIZU, M ROLLER, PP TI DEPROTECTION AND CLEAVAGE METHODS FOR PROTECTED PEPTIDE RESINS CONTAINING 4-[(DIETHYLPHOSPHONO)DIFLUOROMETHYL]-D,L-PHENYLALANINE RESIDUES SO TETRAHEDRON LETTERS LA English DT Article ID SOLID-PHASE SYNTHESIS; RECEPTOR; REAGENT AB Ethyl groups on 4-[(diethylphosphono)difluoromethyl]-D,L-phenylalanine are efficiently removed using S(N)2-type acidic reagents. These methods were utilized for the solid-phase synthesis of SH2-binding peptides containing nonhydrolyzable phosphotyrosyl mimetics. RP OTAKA, A (reprint author), NCI,MED CHEM LAB,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BLDG 37,RM 5C02,BETHESDA,MD 20892, USA. RI Burke, Terrence/N-2601-2014 NR 16 TC 30 Z9 30 U1 0 U2 0 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 29 PY 1993 VL 34 IS 44 BP 7039 EP 7042 DI 10.1016/S0040-4039(00)61591-5 PG 4 WC Chemistry, Organic SC Chemistry GA ME803 UT WOS:A1993ME80300019 ER PT J AU DOBERSTEIN, SK BAINES, IC WIEGAND, G KORN, ED POLLARD, TD AF DOBERSTEIN, SK BAINES, IC WIEGAND, G KORN, ED POLLARD, TD TI INHIBITION OF CONTRACTILE VACUOLE FUNCTION IN-VIVO BY ANTIBODIES AGAINST MYOSIN-I SO NATURE LA English DT Article AB MYOSIN-I is thought to supply the force for movement of cell membranes relative to actin filaments (reviewed in refs 1, 2), but confirmation of this hypothesis has been difficult because of the presence of multiple isoforms of myosin-I and other unconventional myosins in most cells3. We report here the first evidence that a myosin-I isoform is essential for a specific class of intracellular membrane movements in vivo. In Acanthamoeba, the contractile vacuole is an autonomous structure which fuses with the plasma membrane to control the water content of the cell. Because myosin-IC is the only myosin-I isoform concentrated in the contractile vacuole complex4,5 and a protein antigenically related to myosin-IC is located on or near the Dictyostelium (slime mould) contractile vacuole6, we thought this organelle might provide the best opportunity to demonstrate a relationship between myosin-I and membrane motility. Antibodies that inhibit the activity of Acanthamoeba myosin-IC in vitro interfere with expulsion of excess water by the contractile vacuole in vivo, leading to overfilling of this organelle and cell lysis. Myosin-IC may generate the force required to contract the vacuole and may also be involved in transfer of water to the contractile vacuole during refilling. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21225. NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. RP DOBERSTEIN, SK (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT CELL BIOL & ANAT,BALTIMORE,MD 21225, USA. RI Korn, Edward/F-9929-2012 NR 27 TC 106 Z9 107 U1 0 U2 6 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 28 PY 1993 VL 365 IS 6449 BP 841 EP 843 DI 10.1038/365841a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MD951 UT WOS:A1993MD95100051 PM 8413668 ER PT J AU HARRIS, CC HOLLSTEIN, M AF HARRIS, CC HOLLSTEIN, M TI CLINICAL IMPLICATIONS OF THE P53 TUMOR-SUPPRESSOR GENE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID WILD-TYPE P53; BREAST-CANCER PATIENTS; CELL-CYCLE CHECKPOINT; POOR PROGNOSIS; LUNG-CANCER; PROTEIN P53; HEPATOCELLULAR-CARCINOMA; SV40-TRANSFORMED CELLS; MUTATIONAL SPECIFICITY; COLORECTAL-CARCINOMA C1 INT AGCY RES CANC,WHO,MECHANISMS CARCINOGENESIS UNIT,F-69372 LYON,FRANCE. RP HARRIS, CC (reprint author), NCI,HUMAN CARCINOGENESIS LAB,BLDG 37,RM 2C01,BETHESDA,MD 20892, USA. NR 138 TC 1271 Z9 1292 U1 2 U2 22 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 28 PY 1993 VL 329 IS 18 BP 1318 EP 1327 DI 10.1056/NEJM199310283291807 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA MD557 UT WOS:A1993MD55700007 PM 8413413 ER PT J AU BROWN, ML AF BROWN, ML TI SCREENING FOR COLORECTAL-CANCER SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP BROWN, ML (reprint author), NCI,BETHESDA,MD 20892, USA. NR 3 TC 26 Z9 26 U1 1 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 28 PY 1993 VL 329 IS 18 BP 1352 EP 1353 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA MD557 UT WOS:A1993MD55700019 PM 8292163 ER PT J AU WAYSBORT, D TARIEN, E EICHHORN, GL AF WAYSBORT, D TARIEN, E EICHHORN, GL TI NATURE OF THE SPECIFIC INTERACTION OF RHODIUM ACETATE DIMER WITH ADENOSINE SO INORGANIC CHEMISTRY LA English DT Article ID CRYSTAL-STRUCTURE; TRANSFER RNAS; CARBOXYLATES; NUCLEOSIDES; ANTICODON; CONFORMATION; COMPLEXES; ADJACENT; BINDING AB Rhodium acetate dimer [Rh2(Ac)4(H2O)2] reacts specifically with adenosine and not with guanosine, cytidine, or uridine. NMR studies have been conducted in DMSO solution to elucidate the structural basis for this specificity. By the use of various analogues, it was shown that neither N-7 nor N-1 binding can account for the formation of the complex between the rhodium atoms and adenosine in DMSO solution [although the former has been demonstrated in crystals of 1-methyl adenosine with the dimer (from water and methanol) ]. NMR line broadening of C-2, C-6, and C-8, but not of C-4 and C-5, is in line with pi-bonding, A Huckel calculation demonstrates that the former atoms exhibit electron density maxima. The effects of various analogues of adenosine are also in line with pi-bonding. Since guanosine is a poorer pi-acceptor, its inability to react in the manner of adenosine can be explained. The rhodium acetate dimer, unlike the previously studied copper acetate dimer, does not react with the ribose hydroxyl groups of nucleosides. It there fore does not differentiate between ribo- and deoxynucleosides, but is a potential probe of nucleic acid structure by virtue of its base specificity. C1 NIA,GERONTOL RES CTR,CELLULAR & MOLEC BIOL LAB,BALTIMORE,MD 21224. RP WAYSBORT, D (reprint author), ISRAEL INST BIOL RES,POB 19,IL-70450 NESS ZIONA,ISRAEL. NR 41 TC 9 Z9 9 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0020-1669 J9 INORG CHEM JI Inorg. Chem. PD OCT 27 PY 1993 VL 32 IS 22 BP 4774 EP 4779 DI 10.1021/ic00074a020 PG 6 WC Chemistry, Inorganic & Nuclear SC Chemistry GA ME779 UT WOS:A1993ME77900020 ER PT J AU HANCOCK, SL TUCKER, MA HOPPE, RT AF HANCOCK, SL TUCKER, MA HOPPE, RT TI FACTORS AFFECTING LATE MORTALITY FROM HEART-DISEASE AFTER TREATMENT OF HODGKINS-DISEASE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RADIATION-INDUCED PERICARDITIS; MEDIASTINAL IRRADIATION; BREAST-CANCER; CONSTRICTIVE PERICARDITIS; MYOCARDIAL-INFARCTION; CARDIAC DISEASE; RADIOTHERAPY; THERAPY; COMPLICATIONS; ADJUVANT AB Objective.-To assess the risk of death from heart disease after Hodgkin's disease therapy. Design.-Retrospective study comparing treated patients with a matched general population. Setting.-Referral center. Patients.-A total of 2232 consecutive Hodgkin's disease patients treated from 1960 through 1991. Follow-up averaged 9.5 years. Main Outcome Measures.-Relative risks (RRs), the ratio of the observed to the expected cases with 95% confidence intervals (CIs), chi tests for trends, and Kaplan-Meier actuarial risks. Results.-Of the 2232 patients, 88 (3.9%) died of heart disease, 55 from acute myocardial infarction and 33 from other cardiac diseases, including congestive heart failure, radiation pericarditis or pancarditis, cardiomyopathy, or valvular heart disease. The RR for cardiac death was 3.1 (CI, 2.4 to 3.7). Mediastinal radiation of 30 Gy or less (n=385 patients) did not increase risk; above 30 Gy (n=1830), RR was 3.5 (CI, 2.7 to 4.3). Blocking to limit cardiac exposure reduced the RR for other cardiac diseases from 5.3 (CI, 3.1 to 7.5) to 1.4 (CI, 0.6 to 2.9), but not acute myocardial infarction (RR, 3.7 vs 3.4). The RRs increased with duration after treatment (trend in acute myocardial infarction, P=.02; in other cardiac diseases, P=.004). The RR for acute myocardial infarction was highest after irradiation before 20 years of age and decreased with increasing age at treatment (P<.0001 for trend). Conclusions.-Mediastinal irradiation for Hodgkin's disease increases the risk of subsequent death from heart disease. Risk increased with high mediastinal doses, minimal protective cardiac blocking, young age at irradiation, and increasing duration of follow-up. C1 NCI,GENET EPIDEMIOL BRANCH,ROCKVILLE,MD. RP HANCOCK, SL (reprint author), STANFORD UNIV,MED CTR,SCH MED,DEPT RADIAT ONCOL,A089,STANFORD,CA 94305, USA. RI Tucker, Margaret/B-4297-2015 FU NCI NIH HHS [P0: CA-34233] NR 44 TC 437 Z9 449 U1 1 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 27 PY 1993 VL 270 IS 16 BP 1949 EP 1955 DI 10.1001/jama.270.16.1949 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA MC513 UT WOS:A1993MC51300026 PM 8411552 ER PT J AU NUGENT, M HUANG, SM SANDER, M AF NUGENT, M HUANG, SM SANDER, M TI CHARACTERIZATION OF THE APURINIC ENDONUCLEASE ACTIVITY OF DROSOPHILA RRP1 SO BIOCHEMISTRY LA English DT Article ID ENZYME APEX NUCLEASE; ESCHERICHIA-COLI; DNA-REPAIR; EXONUCLEASE-III; APYRIMIDINIC ENDONUCLEASE; DEOXYRIBONUCLEIC-ACID; STRAND TRANSFERASE; HOMOLOGY; PROTEIN; CDNA AB Drosophila Rrp1 (Recombination repair protein 1) belongs to a family of DNA repair nucleases that includes Escherichia coli exonuclease III, Streptococcus pneumoniae exonuclease A, bovine BAP, mouse APEX endonuclease, and human APE. Within a 252 amino acid region, collinear homology is shared between all members. Rrp1 is unique in that it includes a 427 amino acid N-terminal region not related to any known sequence. The protein copurifies with an apurinic endonuclease and a double-stranded DNA 3'-exonuclease. In this study, a 5'-end-labeled 37 base pair oligonucleotide substrate containing a single apurinic site was used to characterize the endonuclease activity of Rrp1. This substrate is utilized efficiently by Rrp1: the specific activity observed is 1 x 10(5) units/mg. The abasic double-stranded DNA oligonucleotide is cleaved only at the abasic site to create a single-strand break. Strand breaks are not detected in the complementary strand, in the single-stranded DNA oligonucleotide, or in the base-paired control substrate. After endonucleolytic cleavage at the abasic site, exonucleolytic processing at the nick is slow and requires a molar excess of Rrp1, while exonuclease III degrades the nicked substrate more efficiently. The Rrp1 cleavage product comigrates with a DNaseI cleavage product, and the newly formed terminus supports DNA synthesis by DNA polymerase. Therefore, Rrp1 cleaves the phosphodiester backbone at one position 5' to the apurinic site and leaves a 3'-hydroxyl terminus. Rrp1 is a class II apurinic endonuclease and is likely to be important in DNA repair in Drosophila. C1 NIEHS,GENET LAB,D3-04,RES TRIANGLE PK,NC 27709. NR 33 TC 12 Z9 12 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 26 PY 1993 VL 32 IS 42 BP 11445 EP 11452 DI 10.1021/bi00093a023 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MD710 UT WOS:A1993MD71000023 PM 7692963 ER PT J AU WU, RM CHIUEH, CC PERT, A MURPHY, DL AF WU, RM CHIUEH, CC PERT, A MURPHY, DL TI APPARENT ANTIOXIDANT EFFECT OF 1-DEPRENYL ON HYDROXYL RADICAL FORMATION AND NIGRAL INJURY ELICITED BY MPP+ IN-VIVO SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE 1-DEPRENYL (SELEGILINE); HYDROXYL RADICAL; DOPAMINE; MPTP NEUROTOXIN; MPP+ (1-METHYL-4-PHENYLPYRIDINIUM ION); SUBSTANTIA-NIGRA; PARKINSONS DISEASE ID PARKINSONS-DISEASE; SUPEROXIDE-DISMUTASE; DOPAMINERGIC SYSTEM; MONOAMINE-OXIDASE; L-DEPRENYL; MAO-B; MPTP; STRIATUM; SALICYLATE; SELEGILINE AB Using a modified microdialysis procedure, we confirmed that intrastriatal administration of 1-methyl-4-phenylpyridinium ion (MPP+) induced a sustained overflow of dopamine accompanied by increased formation of hydroxyl free radicals (.OH) as reflected by salicylate hydroxylation. Pretreatment with 1-deprenyl (selegiline 60 pmol, intrastriatal perfusion) significantly decreased the .OH formation elicited by MPP+ (75 nmol). There was a small decrease of dopamine efflux and an insignificant change of the ratio of 3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine following 1-deprenyl pretreatment. These in vivo findings support prior in vitro data that an unique antioxidant property of 1-deprenyl may be independent of its inhibition of type B monoamine oxidase. In addition, intranigral co-administration of 1-deprenyl (4.2 nmol) with MPP+ (4.2 nmol) completely protected nigral neurons from probable oxidative injuries induced by MPP+ (4.2 nmol), as reflected by a near 50% loss of striatal dopamine ipsilateral to the side of infusion of drug into the substantia nigra. This apparent neuroprotective effect of 1-deprenyl on midbrain nigral neurons was also confirmed by histological findings. The present in vivo data clearly demonstrate that 1-deprenyl can protect nigral neurons against dopamine neurotoxicity produced by MPP+, as suggested by an earlier in vitro study. Thus, 1-deprenyl can preserve the function of MPP+-damaged nigral neurons perhaps by its apparent antioxidant property in addition to its blockade of the bioactivation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to toxic pyridinium metabolites by type B monoamine oxidase. C1 NIMH,CLIN SCI LAB,BLDG 10,ROOM 3D-41,BETHESDA,MD 20892. NATL TAIWAN UNIV HOSP,DEPT NEUROL,TAIPEI 100,TAIWAN. NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 48 TC 150 Z9 154 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD OCT 26 PY 1993 VL 243 IS 3 BP 241 EP 247 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ME295 UT WOS:A1993ME29500005 PM 8276076 ER PT J AU WONDRAK, EM LOUIS, JM DEROCQUIGNY, H CHERMANN, JC ROQUES, BP AF WONDRAK, EM LOUIS, JM DEROCQUIGNY, H CHERMANN, JC ROQUES, BP TI THE GAG PRECURSOR CONTAINS A SPECIFIC HIV-1 PROTEASE CLEAVAGE SITE BETWEEN THE NC (P7) AND P1 PROTEINS SO FEBS LETTERS LA English DT Article DE HUMAN IMMUNODEFICIENCY VIRUS; HIV; NUCLEOCAPSID PROTEIN; NC; P7; PROTEASE ID HUMAN-IMMUNODEFICIENCY-VIRUS; POL POLYPROTEINS; TYPE-1; SALT AB The predicted protease cleavage site (p7/p1; [J. Virol. 66 (1992) 1856-1865]) within the nucleocapsid precursor protein (p15) of human immunodeficiency virus, type 1, was confirmed using an in vitro assay employing recombinant HIV-1 protease and a chemically synthesized 72 amino acid polypeptide containing the p7 and p1 protein domains of the native gag polyprotein. The cleavage occurred between amino acid 55 (N) and amino acid 56 (F) of the polypeptide, as determined by N-terminal sequencing. The hydrolysis was optimal at pH 6.0 and at high salt concentration. The kinetic parameters K(m), k(cat) and k(cat)/K(m) were 99 muM (+/- 8), 0.152 s-1 (+/- 0.002) and 1.56 mM-1 . s-1 (+/- 0.11), respectively. Reconstituted as well as denatured polypeptides were cleaved at approximately the same rate, demonstrating that the conformation of the p7 protein, as a result of the Zn2+-binding, had no significant effect on the rate of hydrolysis of the p7/p1 cleavage. C1 INSERM, U322, UNITE RECH RETROVIRUS & MALAD ASSOCIEES, MARSEILLE, FRANCE. UNIV PARIS 05, UFR SCI PHARMACEUT & BIOL, F-75270 PARIS 06, FRANCE. RP WONDRAK, EM (reprint author), NIDDKD, CELLULAR & DEV BIOL LAB, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 22 TC 35 Z9 35 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 EI 1873-3468 J9 FEBS LETT JI FEBS Lett. PD OCT 25 PY 1993 VL 333 IS 1-2 BP 21 EP 24 DI 10.1016/0014-5793(93)80367-4 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA MC881 UT WOS:A1993MC88100005 PM 8224164 ER PT J AU WISDEN, W PARKER, EM MAHLE, CD GRISEL, DA NOWAK, HP YOCCA, FD FELDER, CC SEEBURG, PH VOIGT, MM AF WISDEN, W PARKER, EM MAHLE, CD GRISEL, DA NOWAK, HP YOCCA, FD FELDER, CC SEEBURG, PH VOIGT, MM TI CLONING AND CHARACTERIZATION OF THE RAT 5-HT(5B)RECEPTOR - EVIDENCE THAT THE 5-HT(5B)RECEPTOR COUPLES TO A G-PROTEIN IN MAMMALIAN-CELL MEMBRANES SO FEBS LETTERS LA English DT Article DE SEROTONIN; 5-HYDROXYTRYPTAMINE; 5-CARBOXAMIDOTRYPTAMINE; G-PROTEIN-COUPLED RECEPTOR; HABENULA; CA1 PYRAMIDAL CELL ID HABENULA; LESION; BRAIN AB A gene encoding a novel G protein-coupled 5-hydroxytryptamine (5-HT) receptor, termed 5-HT5B, was cloned. The ligand binding profile of this receptor is distinct from that of other cloned 5-HT receptors. The 5-HT5B receptor couples to a G protein in COS1 cell membranes; however, activation of the 5-HT5B receptor does not appear to alter either cAMP accumulation or phosphoinositide turnover in a variety of fibroblast cell lines. In the rat brain, 5-HT5B gene expression occurs predominantly in the medial habenulae and hippocampal CA1 cells of the adult. Little expression is seen during embryonic development. C1 NATL UNIV IRELAND UNIV COLL DUBLIN,DEPT PHARMACOL,MERVILLE HOUSE,DUBLIN 4,IRELAND. NATL UNIV IRELAND UNIV COLL DUBLIN,CTR BIOTECHNOL,DUBLIN 4,IRELAND. UNIV HEIDELBERG,ZMBH,CTR MOLEC BIOL,W-6900 HEIDELBERG,GERMANY. BRISTOL MYERS SQUIBB CO,DEPT CNS BIOL,WALLINGFORD,CT 06492. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RI Wisden, William/A-4071-2011 OI Wisden, William/0000-0003-4743-0334 NR 11 TC 54 Z9 55 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD OCT 25 PY 1993 VL 333 IS 1-2 BP 25 EP 31 DI 10.1016/0014-5793(93)80368-5 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA MC881 UT WOS:A1993MC88100006 PM 8224165 ER PT J AU YANG, XJ MILES, EW AF YANG, XJ MILES, EW TI A NOVEL INTERSUBUNIT REPAIR MECHANISM IN THE TRYPTOPHAN SYNTHASE ALPHA(2)BETA(2)-COMPLEX - CRITICAL ROLE OF THE BETA-SUBUNIT LYSINE-167 IN INTERSUBUNIT COMMUNICATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID SITE-SPECIFIC MUTAGENESIS; ESCHERICHIA-COLI; ALPHA-SUBUNIT; BIENZYME COMPLEX; SALMONELLA-TYPHIMURIUM; ALLOSTERIC INTERACTIONS; CONFORMATIONAL-CHANGES; CATALYTIC ACTIVITY; BINDING; ALPHA-2-BETA-2-COMPLEX AB This study explores intersubunit communication in the tryptophan synthase alpha2beta2 complex from Salmonella typhimurium. We find that an engineered mutation in the contact region between the alpha and beta subunits remarkably alters the catalytic and spectroscopic properties of the beta subunit in the alpha2beta2 complex. Ligands that bind to the alpha subunit largely repair the deleterious effects of the beta subunit mutation in the alpha2beta2 complex. The conserved residue chosen for mutation, beta subunit lysine 167, appears to form an ion pair with alpha subunit aspartate 56 in the crystal structure of the wild type alpha2beta2 complex. Although replacement of beta subunit lysine 167 by threonine does not prevent formation of the alpha2beta2 complex, this mutation reduces the rate of synthesis of L-tryptophan from L-serine and indole (beta reaction) 25-fold. Ligands that bind to the alpha subunit (indole-3-glycerol phosphate, indole-3-propanol phosphate, alpha-glycerol 3-phosphate, or potassium phosphate) largely restore the activity of the mutant alpha2beta2 complex in the beta reaction. We conclude that beta subunit lysine 167 plays an important role in intersubunit communication in the alpha2beta2 complex. The striking allosteric effects of alpha subunit ligands on the mutant beta subunit in the alpha2beta2 complex may result from ligand-induced conformational changes in the alpha subunit that are transmitted to the beta subunit and repair the mutational defect in the beta subunit. C1 NIDDKD, BIOCHEM PHARMACOL LAB, BETHESDA, MD 20892 USA. NR 41 TC 25 Z9 25 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 25 PY 1993 VL 268 IS 30 BP 22269 EP 22272 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MD348 UT WOS:A1993MD34800015 PM 8226734 ER PT J AU GOTTESMAN, S CLARK, WP DECRECYLAGARD, V MAURIZI, MR AF GOTTESMAN, S CLARK, WP DECRECYLAGARD, V MAURIZI, MR TI CLPX, AN ALTERNATIVE SUBUNIT FOR THE ATP-DEPENDENT CLP PROTEASE OF ESCHERICHIA-COLI - SEQUENCE AND IN-VIVO ACTIVITIES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LAMBDA-O-PROTEIN; N-END RULE; REGULATORY SUBUNIT; ACTIVATED ATPASE; COLIPHAGE-LAMBDA; PHAGE-LAMBDA; CII PROTEIN; ION GENE; COMPONENT; PROTEOLYSIS AB The ATP-dependent Clp protease of Escherichia coli consists of two subunits, the ClpP subunit, which has the proteolytic active site, and ClpA, which possesses ATPase activity and activates the proteolytic activity of ClpP in vitro. Recently, Zylicz and co-workers (Wojtkowiak, D., Georgopoulos, C., and Zylicz, M. (1993) J. Biol. Chem. 268, 22609-22617) identified another E. coli protein that activated ATP-dependent degradation of lambdaO protein in the presence of ClpP. The amino-terminal sequence of this protein corresponds to the translated amino-terminal sequence of a gene that we have named clpX. clpX encodes a protein with M(r) 46,300, similar to that observed for the protein purified by Wojtkowiak et al. clpX is in an operon with clpP; both genes are cotranscribed in a single heat-inducible 2200-base mRNA, with clpP the promoter proximal gene. The sequence of ClpX includes a single consensus ATP-binding site motif and has limited homology to regions of ClpA and other members of the ClpA/B/C family. A third group of proteins, ClpY, closely related to ClpX, has been identified by sequence homology. Mutations in either clpX or clpP abolish degradation of the highly unstable lambdaO protein in vivo. clpX mutants are not defective in degradation of previously identified ClpA/ClpP substrates such as a ClpA-beta-galactosidase fusion protein. It appears that selectivity of degradation by ClpP in vivo is determined by interaction of ClpP with different regulatory ATPase subunits. RP GOTTESMAN, S (reprint author), NCI,MOLEC BIOL & CELL BIOL LABS,BLDG 37,RM 4B03,BETHESDA,MD 20892, USA. NR 54 TC 254 Z9 258 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 25 PY 1993 VL 268 IS 30 BP 22618 EP 22626 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MD348 UT WOS:A1993MD34800065 PM 8226770 ER PT J AU SANTINI, F BEAVEN, MA AF SANTINI, F BEAVEN, MA TI TYROSINE PHOSPHORYLATION OF A MITOGEN-ACTIVATED PROTEIN KINASE-LIKE PROTEIN OCCURS AT A LATE STEP IN EXOCYTOSIS - STUDIES WITH TYROSINE PHOSPHATASE INHIBITORS AND VARIOUS SECRETAGOGUES IN RAT RBL-2H3 CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; MAST-CELLS; GROWTH-FACTOR; SIGNAL TRANSDUCTION; MAP KINASE; PHOSPHOLIPASE C-GAMMA-1; HISTAMINE-RELEASE; 2H3 CELLS; RECEPTOR; SECRETION AB Several inhibitors of tyrosine phosphatases, which included vanadate/H2O2, phenylarsine oxide, and diamide, blocked exocytosis in basophilic RBL-2H3 cells that had been transfected with the gene for the muscarinic m1 receptor. Because this block was observed whether the secretagogue acted through receptors (i.e. antigen and the muscarinic agonist, carbachol) or by direct activation of intracellular mechanisms (i.e. A23187, A23187 in combination with phorbol 12-myristate 13-acetate, and thapsigargin), the inhibitors appeared to act at a step distal to the mobilization of Ca2+ and activation of protein kinase C. All secretagogues caused the tyrosine phosphorylation of a 40-kDa protein, whereas the inhibitors caused a hyperphosphorylation of this protein. Therefore, both tyrosine kinase and phosphatase activities appear to regulate this phosphorylation which may, in turn, regulate secretion. The 40-kDa protein was identified as a mitogen-activated protein kinase-like protein on the basis of its reactivity to anti-mitogen-activated protein kinase antibodies. In addition, when cells were stimulated the tyrosine phosphorylated and the immunoreactive protein comigrated as a doublet on one-dimensional and as multiple phosphorylated forms on two-dimensional gel-electrophoretic systems. C1 NHLBI,CHEM PHARMACOL LAB,RM 8N114,BLDG 10,BETHESDA,MD 20892. NR 47 TC 76 Z9 76 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 25 PY 1993 VL 268 IS 30 BP 22716 EP 22722 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MD348 UT WOS:A1993MD34800078 PM 7693676 ER PT J AU OTANI, H ERDOS, M LEONARD, WJ AF OTANI, H ERDOS, M LEONARD, WJ TI TYROSINE KINASE(S) REGULATE APOPTOSIS AND BCL-2 EXPRESSION IN A GROWTH FACTOR-DEPENDENT CELL-LINE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA FRAGMENTATION; C-MYC; CHROMOSOMAL BREAKPOINT; CLONAL DELETION; B-CELLS; DEATH; GENE; THYMOCYTES; ACTIVATION; SURVIVAL AB Apoptosis (programmed cell death) plays a critical role in many physiological processes, but the mechanism(s) which regulate apoptosis are poorly understood. We demonstrate that in a hematopoietic cell line, which can grow in either interleukin (IL)-2 or IL-3, both of these growth factors can increase bcl-2 mRNA levels and prevent apoptosis normally seen following growth factor withdrawal. Herbimycin A, a protein tyrosine kinase inhibitor, blocks the ability of IL-2 and IL-3 to up-regulate bcl-2 mRNA levels and induces apoptosis. Transfection of a bcl-2 expression vector not only prolongs survival following growth factor withdrawal but also confers resistance to the effect of herbimycin A. We conclude that herbimycin A-sensitive protein tyrosine kinases are involved in the regulation of apoptosis and bcl-2 expression, but these protein tyrosine kinases appear not to be required for the action of Bcl-2 since Bcl-2 can exert its growth survival effect even in the presence of herbimycin A. C1 NHLBI,OFF DIRECTOR,INTRAMURAL RES PROGRAM,PULM & MOLEC IMMUNOL SECT,BETHESDA,MD 20892. NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. SHIMANE MED UNIV,DEPT ANAT,IZUMO,SHIMANE 693,JAPAN. NR 38 TC 98 Z9 98 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 25 PY 1993 VL 268 IS 30 BP 22733 EP 22736 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MD348 UT WOS:A1993MD34800080 PM 8226783 ER PT J AU PRASAD, R KUMAR, A WIDEN, SG CASASFINET, JR WILSON, SH AF PRASAD, R KUMAR, A WIDEN, SG CASASFINET, JR WILSON, SH TI IDENTIFICATION OF RESIDUES IN THE SINGLE-STRANDED DNA-BINDING SITE OF THE 8-KDA DOMAIN OF RAT DNA POLYMERASE-BETA BY UV CROSS-LINKING SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN; VIRUS REVERSE-TRANSCRIPTASE; ESCHERICHIA-COLI; PRIMER BINDING; DIRECTED MUTAGENESIS; HUMAN-CELLS; PROTEIN; LOCALIZATION; ENZYME; REGION AB Rat DNA polymerase beta (beta-pol) is a 39-kDa monomeric protein, organized in two structurally and functionally distinct domains. The 8-kDa NH-2-terminal domain binds single-stranded (ss) DNA, whereas the 31-kDa COOH-terminal domain does not. To facilitate studies on ssDNA binding structure-function relationships of beta-pol, we overexpressed the 8-kDa domain in Escherichia coli, and purified the recombinant protein to homogeneity. Single-stranded nucleic acid binding of the recombinant 8-kDa domain was found to be similar to that previously reported for the 8-kDa fragment prepared by proteolysis of intact beta-pol (Kumar, A., Widen, S. G., Williams, K. R., Kedar, P., Karpel, R. L., and Wilson, S. H. (1990b) J. Biol. Chem. 265, 2124-2131; Casas-Finet, J. R., Kumar, A., Morris, G., Wilson, S. H., and Karpel, R. L. (1991) J. Biol. Chem. 266, 19618-19625). Residues in or near the DNA-binding pocket of the recombinant 8-kDa domain were examined by photochemical cross-linking to [P-32] p(dT)16. Cross-linking was localized to a tryptic fragment spanning residues 28 through 35 and a V8 protease fragment spanning residues 27 through 58. Sequence analysis of the various [P-32]p(dT)16-labeled proteins indicated that Ser30 and His34 were modified by cross-linking to p(dT)16. Therefore, these residues of the ssDNA-binding domain of beta-pol appear to be in close contact with this nucleic acid probe. C1 UNIV TEXAS,MED BRANCH,SEALY CTR MOLEC SCI,1023 PROFESSIONAL BLDG,H-51,GALVESTON,TX 77555. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,STRUCT BIOCHEM LAB,FREDERICK,MD 21702. NR 40 TC 44 Z9 44 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 25 PY 1993 VL 268 IS 30 BP 22746 EP 22755 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MD348 UT WOS:A1993MD34800082 PM 8226785 ER PT J AU KIRKEN, RA RUI, H EVANS, GA FARRAR, WL AF KIRKEN, RA RUI, H EVANS, GA FARRAR, WL TI CHARACTERIZATION OF AN INTERLEUKIN-2 (IL-2)-INDUCED TYROSINE-PHOSPHORYLATED 116-KDA PROTEIN ASSOCIATED WITH THE IL-2 RECEPTOR BETA-SUBUNIT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COLONY-STIMULATING FACTOR; SIGNAL TRANSDUCTION; ERYTHROPOIETIN RECEPTOR; EXPRESSION CLONING; KINASE ACTIVATION; GAMMA-CHAIN; CELL-LINE; PROLACTIN RECEPTOR; GENE FAMILY; T-CELLS AB In this paper we have extended previous results on interleukin-2 receptor (IL2-R) signal transduction and focused on the interleukin-2 (IL-2)-stimulated tyrosine phosphorylation of a 116-kDa protein (p116) observed in IL-2 responsive cells. This protein exhibited rapid and transient phosphorylation kinetics in both human T-lymphocytes and the YT cell line, attaining maximum tyrosine phosphorylation within 5 min of stimulation with IL-2. Tyrosine phosphorylated p116 co-purified with activated IL-2 receptor beta-chain (IL2-Rbeta) when IL2-R complexes were covalently stabilized with the membrane-permeable cleavable cross-linking agent dithiobis(succimidyl propionate) prior to detergent cell lysis and immunoprecipitation with monoclonal anti-IL2-Rbeta antibodies. Under these conditions comparable amounts of tyrosine-phosphorylated p116 were immuno-precipitated with either anti-IL2-Rbeta antibodies or antiphosphotyrosine antibodies, suggesting that a major portion of tyrosine phosphorylated p116 is associated with the IL2-Rbeta subunit. Furthermore, unphosphorylated p116 was also associated with unactivated IL2-Rbeta, based on the observation that p116 from unstimulated YT cells underwent tyrosine phosphorylation in IL2-Rbeta immune-complex tyrosine kinase assay as demonstrated by anti-phosphotyrosine immunoblotting. The presence of tyrosine kinase activity in affinity-purified IL2-Rbeta complexes supports the notion of a preformed receptor-kinase complex. The co-association of both p116 and tyrosine kinase activity with the IL2-Rbeta supports the critical role of the beta-chain in IL2-R signal transduction and suggests that p116 may have a role in the dynamics of IL2-R activation. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,CYTOKINE MECHANISM SECT,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NR 56 TC 17 Z9 17 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 25 PY 1993 VL 268 IS 30 BP 22765 EP 22770 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MD348 UT WOS:A1993MD34800084 PM 7693677 ER PT J AU STAGSTED, J OLSSON, L HOLMAN, GD CUSHMAN, SW SATOH, S AF STAGSTED, J OLSSON, L HOLMAN, GD CUSHMAN, SW SATOH, S TI INHIBITION OF INTERNALIZATION OF GLUCOSE TRANSPORTERS AND IGF-II RECEPTORS - MECHANISM OF ACTION OF MHC CLASS-I-DERIVED PEPTIDES WHICH AUGMENT THE INSULIN-RESPONSE IN RAT ADIPOSE-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PLASMA-MEMBRANE; HISTOCOMPATIBILITY ANTIGENS; STIMULATED TRANSLOCATION; POTENTIAL MECHANISM; INTRACELLULAR POOL; 3T3-L1 ADIPOCYTES; ASSOCIATION; BINDING; SURFACE; SYSTEMS AB Peptides from the alpha1 domain of the major histocompatibility complex class I antigen (MHC class I), e.g. D(k)-(61-85) and D(k)-(62-85), have been shown previously to augment glucose uptake in insulin-stimulated cells and to inhibit insulin receptor internalization (Stagsted, J., Reaven, G. M., Hansen, T., Goldstein, A., and Olsson, L. (1990) Cell 62, 297-307). We now report that these peptides inhibit by 80-100% the internalization of glucose transporters (GLUT4) and insulin-like growth factor II (IGF-II) receptors in insulin-stimulated cells and correspondingly double insulin-stimulated glucose transport activity and the number of GLUT4 and IGF-II receptors on the cell surface. In addition, the peptides enhance the apparent affinity about 3-fold of IGF-II binding to its receptor. It is concluded that the effects of the peptides on glucose transport and IGF-II binding are a consequence of the peptide-mediated inhibition of internalization of GLUT4 and IGF-II receptor. The active peptides are derived from the alpha1 domain of a MHC class I molecule, suggesting that the latter is involved in regulation of internalization of cell surface integral membrane proteins such as the GLUT4 and IGF-II and insulin receptors. C1 RECEPTRON INC,CONCORD,CA 94520. UNIV BATH,DEPT BIOCHEM,BATH BA2 7AY,AVON,ENGLAND. NIDDKD,DIABET BRANCH,EXPTL DIABET METAB & NUTR SECT,BETHESDA,MD 20892. NR 34 TC 30 Z9 30 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 25 PY 1993 VL 268 IS 30 BP 22809 EP 22813 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MD348 UT WOS:A1993MD34800091 PM 8226791 ER PT J AU BEITNERJOHNSON, D NESTLER, EJ AF BEITNERJOHNSON, D NESTLER, EJ TI CHRONIC MORPHINE IMPAIRS AXOPLASMIC-TRANSPORT IN THE RAT MESOLIMBIC DOPAMINE SYSTEM SO NEUROREPORT LA English DT Article DE VENTRAL TEGMENTAL AREA; NUCLEUS ACCUMBENS; TYROSINE HYDROXYLASE; NEUROFILAMENTS; OPIATE; ADDICTION ID VENTRAL TEGMENTAL AREA; NEUROFILAMENT TRANSPORT; PHOSPHORYLATION; PROTEINS; COCAINE; REGIONS; NERVE AB CHRONIC morphine has been shown to decrease levels of neurofilaments (NFs) in the ventral tegmental area (VTA), which plays a critical role in the rewarding properties of morphine and other drugs of abuse. Since decreased levels of NFs are closely associated with a decrease in slow axonal transport, we studied the effect of chronic morphine on axonal transport in the VTA-nucleus accumbens (NAc) pathway. Chronic morphine decreased axonal transport from the VTA to the NAc by 50%. Chronic morphine did not alter axonal transport from the locus coeruleus to several of its projection areas, consistent with the lack of effect of chronic morphine on NFs in this brain region. C1 NIDDK,DIABET BRANCH,BETHESDA,MD 20892. RP BEITNERJOHNSON, D (reprint author), YALE UNIV,SCH MED,MOLEC PSYCHIAT LAB,NEW HAVEN,CT, USA. NR 17 TC 46 Z9 47 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 25 PY 1993 VL 5 IS 1 BP 57 EP 60 DI 10.1097/00001756-199310000-00014 PG 4 WC Neurosciences SC Neurosciences & Neurology GA ME561 UT WOS:A1993ME56100014 PM 7506589 ER PT J AU ROTHENPIELER, UW DRESSLER, GR AF ROTHENPIELER, UW DRESSLER, GR TI DIFFERENTIAL DISTRIBUTION OF OLIGODEOXYNUCLEOTIDES IN DEVELOPING ORGANS WITH EPITHELIAL-MESENCHYMAL INTERACTIONS SO NUCLEIC ACIDS RESEARCH LA English DT Article ID BRANCHING MORPHOGENESIS; KIDNEY; INHIBITION; CELLS AB The use of antisense oligodeoxynucleotides (ODNs) to inhibit gene expression is a usefull method for determining protein function and has potential therapeutic applications. However, there is still great variability in the successfull application of antisense technology to individual systems. In order to assess the ability of different cell types to take up ODNs, developing embryonic tissues were cultured in vitro in the presence of fluoresceine labelled, phosphorothioate substituted ODNs. The distribution of ODNs in individual cell populations was assayed by fluorescent microscopy and the tissue sections were counterstained for epithelial basement membrane formation. High intracellular levels of ODNs were observed in all mesenchymal cells of the lung, salivary gland, kidney, ovary and testis. However, a significant decrease in ODN levels was observed with the formation of new epithelium in kidney and gonads, whereas mature epithelial cells in all tissues had no detecable levels of ODNs. The ability to inhibit gene expression in mesenchymal cells, but not in epithelial cells, was consistent with the distribution pattern of labeled ODNs. These results may indicate a general resistance of epithelial cells to take up ODNs in culture and bear directly on the ability of ODNs to affect gene expression in complex organs with epithelial components. C1 NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892. NR 22 TC 6 Z9 6 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 1993 VL 21 IS 21 BP 4961 EP 4966 DI 10.1093/nar/21.21.4961 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MF232 UT WOS:A1993MF23200018 PM 8177746 ER PT J AU PUTNEY, JW BIRD, GS AF PUTNEY, JW BIRD, GS TI THE SIGNAL FOR CAPACITATIVE CALCIUM-ENTRY SO CELL LA English DT Article ID INOSITOL 1,4,5-TRISPHOSPHATE; RECEPTOR; RELEASE; CELLS; LOCALIZATION; THAPSIGARGIN RP PUTNEY, JW (reprint author), NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709, USA. NR 17 TC 414 Z9 415 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD OCT 22 PY 1993 VL 75 IS 2 BP 199 EP 201 DI 10.1016/0092-8674(93)80061-I PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MD885 UT WOS:A1993MD88500001 PM 8402906 ER PT J AU STROBER, W EHRHARDT, RO AF STROBER, W EHRHARDT, RO TI CHRONIC INTESTINAL INFLAMMATION - AN UNEXPECTED OUTCOME IN CYTOKINE OR T-CELL RECEPTOR MUTANT MICE SO CELL LA English DT Article ID BOWEL-DISEASE; CROHNS-DISEASE; INTERLEUKIN-2; LYMPHOCYTES; MUCOSA RP STROBER, W (reprint author), NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BETHESDA,MD 20892, USA. NR 17 TC 163 Z9 165 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD OCT 22 PY 1993 VL 75 IS 2 BP 203 EP 205 DI 10.1016/0092-8674(93)80062-J PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MD885 UT WOS:A1993MD88500002 PM 8402907 ER PT J AU SCHECHTER, AN AF SCHECHTER, AN TI THE NIH INTRAMURAL PROGRAM SO SCIENCE LA English DT Letter C1 NIDDKD,BETHESDA,MD 20892. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 22 PY 1993 VL 262 IS 5133 BP 489 EP 489 DI 10.1126/science.8211166 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MC935 UT WOS:A1993MC93500002 PM 8211166 ER PT J AU WIVEL, NA WALTERS, L AF WIVEL, NA WALTERS, L TI GERM-LINE GENE MODIFICATION AND DISEASE PREVENTION - SOME MEDICAL AND ETHICAL PERSPECTIVES SO SCIENCE LA English DT Article ID TRANSGENIC MICE; MOUSE EMBRYOS; BETA-THALASSEMIA; CYSTIC-FIBROSIS; POINT MUTATION; ANIMAL-MODEL; THERAPY; RETINOBLASTOMA; EXPRESSION; DEFICIENCY AB There has been considerable debate about the ethics of human germ-line gene modification. As a result of recent advances in the micromanipulation of embryos and the laboratory development of transgenic mice, a lively discussion has begun concerning both the technical feasibility and the ethical acceptability of human germ-line modification for the prevention of serious disease. This article summarizes some of the recent research on germ-line gene modification in animal models. Certain monogenic deficiency diseases that ultimately might be candidates for correction by germ-line intervention are identified. Several of the most frequently considered ethical issues relative to human germ-line gene modification are considered in the context of professional ethics, parental responsibility, and public policy. Finally, it is suggested that there is merit in continuing the discussion about human germ-line intervention, so that this technique can be carefully compared with alternative strategies for preventing genetic disease. C1 GEORGETOWN UNIV,KENNEDY INST ETHICS,WASHINGTON,DC 20057. RP WIVEL, NA (reprint author), NIH,OFF RECOMBINANT DNA ACT,BETHESDA,MD 20892, USA. NR 90 TC 48 Z9 49 U1 6 U2 14 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 22 PY 1993 VL 262 IS 5133 BP 533 EP 538 DI 10.1126/science.8211180 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MC935 UT WOS:A1993MC93500030 PM 8211180 ER PT J AU LEI, KJ SHELLY, LL PAN, CJ SIDBURY, JB CHOU, JY AF LEI, KJ SHELLY, LL PAN, CJ SIDBURY, JB CHOU, JY TI MUTATIONS IN THE GLUCOSE-6-PHOSPHATASE GENE THAT CAUSE GLYCOGEN-STORAGE-DISEASE TYPE-1A SO SCIENCE LA English DT Article ID MICROSOMAL GLUCOSE-6-PHOSPHATASE; MULTIFUNCTIONAL GLUCOSE-6-PHOSPHATASE; ENDOPLASMIC-RETICULUM; SYSTEM; SPECIFICITY; PROTEINS AB Glycogen storage disease (GSD) type 1a is caused by the deficiency Of D-glucose-6-phosphatase (G6Pase), the key enzyme in glucose homeostasis. Despite both a high incidence and morbidity, the molecular mechanisms underlying this deficiency have eluded characterization. In the present study, the molecular and biochemical characterization of the human G6Pase complementary DNA, its gene, and the expressed protein, which is indistinguishable from human microsomal G6Pase, are reported. Several mutations in the G6Pase gene of affected individuals that completely inactivate the enzyme have been identified. These results establish the molecular basis of this disease and open the way for future gene therapy. C1 NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. NR 24 TC 263 Z9 273 U1 4 U2 14 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 22 PY 1993 VL 262 IS 5133 BP 580 EP 583 DI 10.1126/science.8211187 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MC935 UT WOS:A1993MC93500045 PM 8211187 ER PT J AU CHOW, WH MCLAUGHLIN, JK HRUBEC, Z NAM, JM BLOT, WJ AF CHOW, WH MCLAUGHLIN, JK HRUBEC, Z NAM, JM BLOT, WJ TI TOBACCO USE AND NASOPHARYNGEAL CARCINOMA IN A COHORT OF UNITED-STATES VETERANS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID ENVIRONMENTAL RISK-FACTORS; EPSTEIN-BARR-VIRUS; CIGARETTE-SMOKING; UNITED-STATES; SALTED FISH; HONG-KONG; CANCER; DEATH; CHINA AB The risk of nasopharyngeal carcinoma (NPC), a relatively rare neoplasm in the United States, was examined in relation to tobacco use in a cohort of nearly 250,000 US veterans whose mortality experience was followed for 26 years. A total of 48 NPC deaths were identified during the follow-up period. Current smokers had a nearly 4-fold increase in risk of NPC compared with non-users of any tobacco, with risk increasing to 6.4 among those smoking more than 2 packs daily. After adjustment for age and number of cigarettes smoked, risks were inversely associated with age at starting to smoke, with the highest risk observed among those who started smoking before age 15, although no clear trend associated with duration of smoking was observed. Former cigarette smokers had a small excess risk of NPC, but no association was detected for cigar/pipe users. This study adds strong evidence to the increasing literature linking cigarette smoking to NPC. (C) 1993 Wiley-Liss, Inc. RP CHOW, WH (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,6130 EXECUTIVE BLVD,BETHESDA,MD 20892, USA. NR 33 TC 51 Z9 51 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD OCT 21 PY 1993 VL 55 IS 4 BP 538 EP 540 DI 10.1002/ijc.2910550403 PG 3 WC Oncology SC Oncology GA ME125 UT WOS:A1993ME12500002 PM 8406978 ER PT J AU LIU, FS DAWSEY, SM WANG, GQ RAO, M LIPKIN, M LEWIN, KJ LI, JY LI, B TAYLOR, PR AF LIU, FS DAWSEY, SM WANG, GQ RAO, M LIPKIN, M LEWIN, KJ LI, JY LI, B TAYLOR, PR TI CORRELATION OF EPITHELIAL PROLIFERATION AND SQUAMOUS ESOPHAGEAL HISTOLOGY IN 1185 BIOPSIES FROM LINXIAN, CHINA SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID CANCER; RISK; POPULATIONS; LESIONS; CELLS; IRAN AB Epithelial proliferation is an active area of research in gastrointestinal cancer, but only a few studies have examined the relationship of esophageal epithelial proliferation and squamous histologic findings in populations with high rates of squamous esophageal cancer. In order to study this correlation, tritiated thymidine labeling was performed on 1185 esophageal biopsies from 745 residents of Linxian, China, a county with some of the highest esophageal-cancer rates in the world. Total labeling index (TLI = total labeled cells/total cells counted) was used to measure the amount of proliferation, and the proportion of labeled cells found in cell layers 4 to 10 (labeled cell fraction 4 plus, LF4+ = labeled cells in layers 4-10/total labeled cells) was used to measure the vertical distribution of proliferation. Of the biopsies, 979 were histologically normal, 51 showed acanthosis, 35 showed esophagitis, 116 showed squamous dysplasia, and 6 showed invasive squamous cancer. The mean values of both proliferation variables, stratified by histologic diagnosis, showed the following relationships: normal = acanthosis < esophagitis = dysplasia < cancer. The ranges of proliferation values overlapped extensively in all biopsy categories, so that measuring proliferation could not substitute for histologic diagnosis. It remains to be seen whether proliferation values, histologic diagnoses, or some combination of these methods is most predictive of subsequent esophageal cancer. (C) 1993 Wiley-Liss, Inc. C1 NCI, DIV CANC PREVENT & CONTROL, CANC PREVENT STUDIES BRANCH, BETHESDA, MD 20892 USA. CHINESE ACAD MED SCI, INST CANC, BEIJING, PEOPLES R CHINA. MEM SLOAN KETTERING CANC CTR, NEW YORK, NY 10021 USA. UNIV CALIF LOS ANGELES, CTR HLTH SCI, LOS ANGELES, CA USA. CHINA CANC RES FDN, BEIJING, PEOPLES R CHINA. NR 13 TC 4 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD OCT 21 PY 1993 VL 55 IS 4 BP 577 EP 579 DI 10.1002/ijc.2910550410 PG 3 WC Oncology SC Oncology GA ME125 UT WOS:A1993ME12500009 PM 8406984 ER PT J AU HAMER, D AF HAMER, D TI SEXUAL ORIENTATION SO NATURE LA English DT Letter RP HAMER, D (reprint author), NCI,BIOCHEM LAB,BETHESDA,MD 20892, USA. NR 2 TC 1 Z9 1 U1 0 U2 2 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 21 PY 1993 VL 365 IS 6448 BP 702 EP 702 DI 10.1038/365702b0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MC812 UT WOS:A1993MC81200044 PM 8280262 ER PT J AU PIZZO, PA AF PIZZO, PA TI FEVER IN PATIENTS WITH NEUTROPENIA - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP PIZZO, PA (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 21 PY 1993 VL 329 IS 17 BP 1280 EP 1280 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MB988 UT WOS:A1993MB98800031 ER PT J AU SCHMITT, JM KNUTTEL, A BONNER, RF AF SCHMITT, JM KNUTTEL, A BONNER, RF TI MEASUREMENT OF OPTICAL-PROPERTIES OF BIOLOGICAL TISSUES BY LOW-COHERENCE REFLECTOMETRY SO APPLIED OPTICS LA English DT Article DE INTERFEROMETRY; LOW COHERENCE; BIOMEDICAL OPTICS ID SCATTERING PHASE FUNCTIONS; MULTIPLE-SCATTERING; RESOLUTION; MEDIA; BACKSCATTERING; COEFFICIENTS; LIGHT AB We show that optical properties of dense biological tissues can be determined from backscattered power curves measured by a low-coherence reflectometer. Our measurement approach is based on a first-order scattering theory that relates the backscattered power to the total and backscattering cross sections of scatterers in a turbid medium. As a validation of the technique, measurements were made with a commercially available reflectometer on suspensions of polystyrene microspheres having known optical properties. With this reflectometer, which employs a 1300-nm LED source that emits less than 20 muW, we found that skin tissues could be probed to a depth of nearly 1 mm. Estimates of optical coefficients of human dermis and of a variety of excised animal tissues are given. C1 NHLBI, CARDIAC ENERGET LAB, BETHESDA, MD 20892 USA. RP SCHMITT, JM (reprint author), NIH, NATL CTR RES RESOURCES, BIOMED ENGN & INSTRUMENTAT PROGRAM, BETHESDA, MD 20892 USA. RI Bonner, Robert/C-6783-2015 NR 31 TC 239 Z9 252 U1 1 U2 26 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0003-6935 J9 APPL OPTICS JI Appl. Optics PD OCT 20 PY 1993 VL 32 IS 30 BP 6032 EP 6042 PG 11 WC Optics SC Optics GA MC053 UT WOS:A1993MC05300026 PM 20856430 ER PT J AU KOH, WJ KRALL, JM PETERS, LJ MAOR, MH LARAMORE, GE BURNISON, CM DAVIS, LW ZINK, S GRIFFIN, TW AF KOH, WJ KRALL, JM PETERS, LJ MAOR, MH LARAMORE, GE BURNISON, CM DAVIS, LW ZINK, S GRIFFIN, TW TI NEUTRON VS PHOTON RADIATION-THERAPY FOR INOPERABLE REGIONAL NONSMALL CELL LUNG-CANCER - RESULTS OF A MULTICENTER RANDOMIZED TRIAL SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE NONSMALL CELL LUNG CANCER; NEUTRON RADIOTHERAPY; PHOTON RADIOTHERAPY; MULTICENTER RANDOMIZED CLINICAL TRIAL ID ONCOLOGY-GROUP; CARCINOMA; RADIOTHERAPY AB Purpose: To determine, with a prospective, multicenter randomized study, whether fast neutron radiation therapy improves the outcome for patients with non-small cell lung cancer, as compared to conventional photon radiotherapy. Methods and Materials: From September 1986 to March 1991, a total of 200 patients with inoperable regional non-small cell lung cancer were randomized to 20.4 Gy in 12 fractions with neutrons versus 66 Gy in 33 fractions with photons. Inoperable patients with Radiation Therapy Oncology Group Stages I, II, III, or IV(MO) disease, Karnofsky Performance Score greater-than-or-equal-to 70, and who had received no previous therapy for their non-small cell lung cancer were eligible for the study. Of the 200 patients randomized, a total of 193 patients, 99 on the neutron arm and 94 on the photon arm, were eligible for analysis. The two treatment groups were balanced with regards to prognostic factors. At the time of this analysis, the median at-risk follow-up was 33 months, with a minimum follow-up of 16 months. Results: No difference in overall survival was observed; however, there was a statistically significant improvement in survival for patients with squamous cell histology (p = 0.02), and a trend toward improved survival for those with favorable prognostic factors (i.e., patients who were not T4, N3, and had no pleural effusion or weight loss > 5% from baseline) (p = 0.15), favoring the neutron-treated group. With the exception of skin and subcutaneous changes, acute and late toxicity was similar in both arms. Conclusion: In selected patients with inoperable regional non-small cell lung cancer (e.g., squamous cell histology, favorable prognostic factors), fast neutron irradiation provides a therapeutic benefit over conventional photon radiotherapy. C1 AMER COLL RADIOL, STAT UNIT, PHILADELPHIA, PA 19107 USA. UNIV TEXAS, MD ANDERSON CANC CTR, HOUSTON, TX 77030 USA. UNIV CALIF LOS ANGELES, DEPT RADIAT ONCOL, LOS ANGELES, CA 90024 USA. EMORY CLIN, DEPT RADIAT ONCOL, ATLANTA, GA 30322 USA. NCI, RADIAT RES PROGRAM, BETHESDA, MD 20892 USA. RP KOH, WJ (reprint author), UNIV WASHINGTON, MED CTR, DEPT RADIAT ONCOL, RC-08, 1959 NE PACIFIC ST, SEATTLE, WA 98195 USA. NR 20 TC 22 Z9 22 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 20 PY 1993 VL 27 IS 3 BP 499 EP 505 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA MF620 UT WOS:A1993MF62000002 PM 8226141 ER PT J AU JOHNSTONE, PAS PIERCE, LJ MERINO, MJ YANG, JC EPSTEIN, AH DELANEY, TF AF JOHNSTONE, PAS PIERCE, LJ MERINO, MJ YANG, JC EPSTEIN, AH DELANEY, TF TI PRIMARY SOFT-TISSUE SARCOMAS OF THE BREAST - LOCAL-REGIONAL CONTROL WITH POSTOPERATIVE RADIOTHERAPY SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Note DE ADJUVANT THERAPY; BREAST; MASTECTOMY; RADIOTHERAPY; SOFT TISSUE SARCOMAS ID ADJUVANT CHEMOTHERAPY; ANGIOSARCOMA AB Purpose: A retrospective analysis was undertaken to determine the efficacy of postoperative radiotherapy in patients with primary sarcoma of the breast. Methods and Materials: Ten patients with high-grade nonmetastatic primary sarcoma of the breast were treated at the National Cancer Institute, NIH, between 1979 and 1989 with mastectomy and adjuvant radiotherapy. Chemotherapy was given to three patients as part of a randomized trial. Results: With a median potential followup of '' months postoperatively, seven patients remain alive and without evidence of disease 142, 119, 82, 48, 45, 28, and 19 months postoperatively. Three patients died of metastatic disease 7, 25, and 29 months, postoperatively. There were no local or regional failures. Actuarial 5-year disease free and overall survival were 68% and 66%, respectively. Conclusion: Sarcomas of the breast have a prognosis similar to that of extremity sarcomas. When adjuvant radiotherapy is used, excellent local control may be achieved. C1 NCI,RADIAT ONCOL BRANCH,BLDG 10,RM B3B69,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. NR 18 TC 32 Z9 33 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 20 PY 1993 VL 27 IS 3 BP 671 EP 675 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA MF620 UT WOS:A1993MF62000025 PM 8226163 ER PT J AU PSATY, BM SAVAGE, PJ TELL, GS POLAK, JF HIRSCH, CH GARDIN, JM MCDONALD, RH AF PSATY, BM SAVAGE, PJ TELL, GS POLAK, JF HIRSCH, CH GARDIN, JM MCDONALD, RH TI TEMPORAL PATTERNS OF ANTIHYPERTENSIVE MEDICATION USE AMONG ELDERLY PATIENTS - THE CARDIOVASCULAR HEALTH STUDY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID BLOOD-PRESSURE; HYPERTENSION; EXPERIENCE; GLUCOSE; THERAPY; TRIAL AB Objectives.-To estimate the incidence of newly treated hypertension and to describe the patterns of antihypertensive medication use among those aged 65 years and older. Design.-Medicare eligibility lists from four US communities (Forsyth County, North Carolina; Washington County, Maryland; Sacramento County, California; and Pittsburgh, Pa) were used to obtain a representative sample of 5201 community-dwelling elderly for the Cardiovascular Health Study, a prospective cohort study of risk factors for coronary heart disease and stroke. Participants were examined at baseline and again 1 year later. The two examinations included standardized questionnaires, blood pressure measurements, and the assessment of medication use by medication inventory. In this cohort analysis, we excluded 231 subjects (4.4%) who did not return for follow-up, 69 (1.3%) who had missing data for medications, and another 495 (9.5%) who were taking ''antihypertensive'' medications for an indication other than high blood pressure. Interventions.-None. Results.-Among the 4406 participants, 1613 used antihypertensive medications at both visits. Between the two visits, 144 started and 115 stopped antihypertensive therapy. Among nonusers at baseline, the annual incidence of newly treated hypertension was 5.2% in women and 5.6% in men. Due to the number of participants who stopped therapy, the overall prevalence of antihypertensive treatment increased only slightly, from 40.7% to 41.1% in women and from 37.1% to 38.2% in men, during 1 year of follow-up. After adjustment for age, systolic blood pressure, number of antihypertensive drugs, diabetes, and cardiovascular disease, the newly treated hypertensives were about half as likely as the previously treated hypertensives to receive diuretics (odds ratio [OR], 0.59; P=.008) or beta-blockers (OR, 0.52; P=.01); and they were about twice as likely to receive calcium channel blockers (OR, 1.88; P<.004) or angiotensin converting enzyme inhibitors (OR, 2.40; P<.001). A similar pattern of within-person changes over time was apparent among the continuous users. Conclusions.-Between June 1990 and June 1991, physicians were increasingly prescribing angiotensin converting enzyme inhibitors and calcium channel blockers in place of diuretics and beta-blockers for the treatment of hypertension in elderly patients, especially for those just starting therapy. C1 UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT EPIDEMIOL,SEATTLE,WA 98195. UNIV PITTSBURGH,DEPT EPIDEMIOL,PITTSBURGH,PA 15260. UNIV WASHINGTON,DEPT HLTH SERV,SEATTLE,WA 98195. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,EPIDEMIOL & BIOMETRY PROGRAM,BETHESDA,MD 20892. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. BRIGHAM & WOMENS HOSP,DEPT RADIOL,BOSTON,MA 02115. UNIV CALIF DAVIS,SACRAMENTO MED CTR,DEPT MED,SACRAMENTO,CA 95817. UNIV CALIF IRVINE,DEPT MED,IRVINE,CA 92717. RP PSATY, BM (reprint author), CARDIOVASC HLTH STUDY,CTR COORDINATING,CENTURY SQ,SUITE 2025,1501 4TH AVE,SEATTLE,WA 98101, USA. RI Tell, Grethe/G-5639-2015 OI Tell, Grethe/0000-0003-1386-1638 FU NHLBI NIH HHS [HL-43201, N01-HC-85079, N01-HC-85086] NR 28 TC 61 Z9 61 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 20 PY 1993 VL 270 IS 15 BP 1837 EP 1841 DI 10.1001/jama.270.15.1837 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA MB464 UT WOS:A1993MB46400027 PM 8105112 ER PT J AU KLEINMAN, D ROBERTS, CT LEROITH, D SCHALLY, AV LEVY, J SHARONI, Y AF KLEINMAN, D ROBERTS, CT LEROITH, D SCHALLY, AV LEVY, J SHARONI, Y TI REGULATION OF ENDOMETRIAL CANCER CELL-GROWTH BY INSULIN-LIKE GROWTH-FACTORS AND THE LUTEINIZING-HORMONE-RELEASING HORMONE ANTAGONIST SB-75 SO REGULATORY PEPTIDES LA English DT Article DE LUTEINIZING HORMONE-RELEASING HORMONE; INSULIN-LIKE GROWTH FACTOR; ANTAGONIST; CANCER CELL GROWTH ID BREAST-CANCER; FACTOR-I; POTENT ANTAGONISTS; MAMMARY-TUMOR; IGF-II; INHIBITION; AGONISTS; RECEPTORS; SECRETION; ANALOG AB The involvement of IGFs in growth regulation of the Ishikawa endometrial tumor cell line and the possible interference of LH-RH analogues with a potential autocrine or paracrine loop involving IGFs was evaluated. The mitogenic effects of IGF-I, IGF-II, and insulin were compared. IGF-I was found to be 3-fold more potent than IGF-II and 30-fold more potent than insulin, suggesting that the effects of these growth factors are mediated by the IGF-I receptor. Ishikawa endometrial cancer cells secrete IGF-II, but not IGF-I, and insulin (1 muM) stimulates IGF-II release. The LH-RH antagonist [AC-D-Nal(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala10]-GnRH (SB-75, CETRORELIX) inhibited basal and IGF-induced growth. Moreover, this antagonist almost completely inhibited IGF-II release from Ishikawa cells, while having no significant effect on the number or affinity of IGF-I binding sites. Inhibition of IGF-II release occurred at a lower SB-75 concentration than that needed for a reduction in cell number. The ED50 of SB-75 for IGF-II release was 0.3 muM as compared to 1.5 mum concentration which is required for reduction in cell number, suggesting that inhibition of growth factor release precedes cell growth inhibition. We conclude that the LH-RH antagonist SB-75 can inhibit the growth of endometrial cancer cells by interfering with the autocrine action of IGF-II and also by directly inhibiting the growth-stimulatory effects of IGFs, probably through effects on a post-receptor mechanism. C1 BEN GURION UNIV NEGEV,SOROKA MED CTR KUPAT HOLIM,FAC HLTH SCI,DEPT CLIN BIOCHEM,IL-84105 BEER SHEVA,ISRAEL. NIDDK,DIABET BRANCH,BETHESDA,MD. TULANE UNIV,SCH MED,VET ADM MED CTR,INST ENDOCRINE POLYPEPTIDE & CANC,NEW ORLEANS,LA 70112. TULANE UNIV,SCH MED,DEPT MED,NEW ORLEANS,LA 70112. OI Roberts, Charles/0000-0003-1756-5772; Schally, Andrew/0000-0003-1273-6747 NR 34 TC 40 Z9 41 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD OCT 20 PY 1993 VL 48 IS 1-2 BP 91 EP 98 DI 10.1016/0167-0115(93)90338-9 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA MD637 UT WOS:A1993MD63700010 PM 8265821 ER PT J AU YANG, YWH BROWN, DR ROBCIS, HL RECHLER, MM DEPABLO, F AF YANG, YWH BROWN, DR ROBCIS, HL RECHLER, MM DEPABLO, F TI DEVELOPMENTAL REGULATION OF INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-2 IN CHICK-EMBRYO SERUM AND VITREOUS-HUMOR SO REGULATORY PEPTIDES LA English DT Article DE IGF BINDING PROTEIN-2; DEVELOPMENT; REGULATION; CHICK EMBRYO ID IGF-I GENE; DEVELOPING LENS; EXPRESSION; RECEPTORS; TISSUES; CLONING; IGFBP-2; EYE AB The chick embryo is a useful vertebrate model for studying developmental embryogenesis. Insulin-like growth factor I (IGF-I), a potent mitogen, is thought to contribute to the general growth of the embryo as an endocrine factor, and as a paracrine factor to the development of the early embryo and of specific organs such as the eye. Recent data suggest that a family of at least six IGF binding proteins (IGFBPs) complex IGF-I and modulate its biological actions. In the present study, we examine the expression of IGFBPs in chicken serum and vitreous humor at different stages of embryonic development, and compare it with that of IGF-I. As determined by ligand blotting, the predominant IGFBP in chick serum and vitreous humor between embryonic days 4 and 22 (E4-E22) is a 30 kDa IGFBP. This IGFBP was specifically immunoprecipitated by a polyclonal antiserum raised against rat IGFBP-2, the predominant IGFBP in fetal human and rat serum. Although IGFBP-2 is present in both chick fluids at all times examined, serum IGFBP-2 increased progressively between E10-E22, whereas vitreous IGFBP-2 was highest during eye organogenesis (E4-E8). This suggests that vitreous IGFBP-2 is synthesized locally. Like serum IGFBP-2, levels of immunoreactive IGF-I in serum are higher in the second week of embryogenesis than the first. Despite this correlation, changes in IGFBP-2 do not appear to be regulated by IGF-1: (a) serum IGF-I decreases after day 15, whereas IGFBP-2 levels remain stable until hatching; (b) vitreous IGF-1, like serum IGF-I, is higher in the second week of embryogenesis, whereas vitreous IGFBP-2 is highest in the first week; (c) embryos cultured ex ovo express IGFBP-2 at E15-E19, although they lack the normal mid-embryogenesis surge in IGF-I. We conclude that vitreous IGFBP-2 is synthesized locally in the eye, and that the expression of IGFBP-2 in chick embryos is not directly regulated by IGF-I. C1 NIH,NCRR,VET RESOURCES PROGRAM,BETHESDA,MD 20892. CSIC,CTR INVEST BIOL,MADRID 6,SPAIN. RP YANG, YWH (reprint author), NIDDK,MOLEC & CELLULAR ENDOCRINOL BRANCH,GROWTH & DEV SECT,BLDG 10,RM 8D-14,BETHESDA,MD 20892, USA. NR 40 TC 25 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD OCT 20 PY 1993 VL 48 IS 1-2 BP 145 EP 155 DI 10.1016/0167-0115(93)90343-7 PG 11 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA MD637 UT WOS:A1993MD63700015 PM 7505461 ER PT J AU LOPACZYNSKI, W HARRIS, S NISSLEY, P AF LOPACZYNSKI, W HARRIS, S NISSLEY, P TI INSULIN-LIKE GROWTH FACTOR-I (IGF-I) DEPENDENT PHOSPHORYLATION OF THE IGF-I RECEPTOR IN MG-63 CELLS SO REGULATORY PEPTIDES LA English DT Article DE IGF-I RECEPTOR; PURIFICATION; TYROSINE PHOSPHORYLATION; MONOCLONAL ANTIBODY ID TYROSINE KINASE-ACTIVITY; BETA-SUBUNIT; SIGNAL TRANSDUCTION; SOMATOMEDIN-C; SUBSTRATE; PROTEINS; COMMON; IRS-1; AUTOPHOSPHORYLATION; THYROTROPIN AB Insulin-like growth factor I (IGF-I) stimulates multiplication of the human osteosarcoma cell line, MG-63. by acting through the IGF-I receptor. We have characterized IGF-I stimulated phosphorylation of the IGF-I receptor in this cell line. Serum starved MG-63 cells were metabolically labeled with [P-32]orthophosphoric acid and the cells were treated with IGF-I. Phosphotyrosine containing proteins were immunoprecipitated from the cell lysates with antiphosphotyrosine-Agarose and eluted with phenyl phosphate. Further immmunoprecipitation with IGF-I receptor monoclonal antibodies (alphaIR-3, 18E9) and analysis by sodium dodecylsulfate polyacrylamide gel electrophoresis and autoradiography demonstrated IGF-I dependent autophosphorylation of the IGF-I receptor. Phosphoamino acid analysis of the IGF-I receptor beta subunit and the observation that antiphosphotyrosine-Agarose did not immunoprecipitate [S-35]methionine-labeled receptor from unstimulated cells, demonstrated that in the absence of IGF-I, the receptor was not phosphorylated on tyrosine residues. Western blotting of cell lysates with a monoclonal phosphotyrosine antibody did not identify the IGF-I receptor or pp185 but demonstrated IGF-I dependent phosphorylation on tyrosine residues in three other proteins, p110, p70 and p40. C1 NCI,ENDOCRINOL SECT,METAB BRANCH,BLDG 10,RM 4N115,9001 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 28 TC 15 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD OCT 20 PY 1993 VL 48 IS 1-2 BP 207 EP 216 DI 10.1016/0167-0115(93)90349-D PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA MD637 UT WOS:A1993MD63700021 PM 7505467 ER PT J AU GENTRY, DR BURGESS, RR AF GENTRY, DR BURGESS, RR TI CROSS-LINKING OF ESCHERICHIA-COLI RNA-POLYMERASE SUBUNITS - IDENTIFICATION OF BETA' AS THE BINDING-SITE OF OMEGA SO BIOCHEMISTRY LA English DT Article ID TRANSCRIPTION; SPOT; GENE; MUTANTS; OPERON; K-12; MUTATIONS; PROTEIN; RECG; DNA AB The omega protein is a peptide found in near-stoichiometric levels in highly purified Escherichia coli RNA polymerase. In order to determine the binding site of omega to RNA polymerase, we cross-linked omega to RNA polymerase with the hetero-bifunctional cross-linker N-hydroxysuccinimidyl 4-azidobenzoate and analyzed for cross-linked partners using antibodies raised against each of the subunits. Our analysis indicates that omega cross-links predominately with the beta' subunit, while a very low level of cross-linking was detected to the alpha subunit. We did not detect cross-linking to either the sigma70 or the beta subunits. This report demonstrates the utility of combining cross-linking and immunological techniques to determine interactions between RNA polymerase subunits. C1 UNIV WISCONSIN,MCARDLE LAB CANC RES,MADISON,WI 53706. RP GENTRY, DR (reprint author), NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA07175]; NIGMS NIH HHS [GM28575] NR 30 TC 31 Z9 31 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 19 PY 1993 VL 32 IS 41 BP 11224 EP 11227 DI 10.1021/bi00092a036 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MC569 UT WOS:A1993MC56900035 PM 8218187 ER PT J AU HEIDBREDER, C GOLDBERG, SR SHIPPENBERG, TS AF HEIDBREDER, C GOLDBERG, SR SHIPPENBERG, TS TI INHIBITION OF COCAINE-INDUCED SENSITIZATION BY THE DELTA-OPIOID RECEPTOR ANTAGONIST NALTRINDOLE SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE COCAINE; SENSITIZATION; NALTRINDOLE; LOCOMOTOR ACTIVITY; OPIOIDS ID NUCLEUS-ACCUMBENS; DOPAMINE RELEASE; MESSENGER-RNA; OPIATE; RAT; EXPRESSION AB The influence of the delta-opioid receptor antagonist naltrindole upon sensitization to the locomotor activating effects of cocaine was assessed. Activity in response to a challenge dose of cocaine (20 mg/kg, i.p.) was significantly increased in rats which had received cocaine (20 mg/kg, i.p.) once daily for 3 days as compared to those which had previously received saline. The repeated administration of naltrindole (0.3-3.0 mg/kg, s.c.) alone did not affect activity. However, in animals which had received both naltrindole and cocaine for 3 days, no sensitization to the locomotor activating effects of cocaine was observed. These data demonstrate that the selective blockade of delta-opioid receptors modifies the development of cocaine-induced sensitization and suggest an important role of delta-opioid receptor Systems in modulating the development of drug-induced sensitization. C1 NIDA,ADDICT RES CTR,PRECLIN PHARMACOL LAB,BEHAV PHARMACOL & GENET SECT,POB 5180,BALTIMORE,MD 21224. NR 20 TC 39 Z9 40 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD OCT 19 PY 1993 VL 243 IS 2 BP 123 EP 127 DI 10.1016/0014-2999(93)90370-W PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MD138 UT WOS:A1993MD13800003 PM 8276060 ER PT J AU IZENWASSER, S NEWMAN, AH KATZ, JL AF IZENWASSER, S NEWMAN, AH KATZ, JL TI COCAINE AND SEVERAL SIGMA-RECEPTOR LIGANDS INHIBIT DOPAMINE UPTAKE IN RAT CAUDATE-PUTAMEN SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Note DE DOPAMINE UPTAKE; COCAINE; CAUDATE-PUTAMEN; SIGMA-RECEPTORS; RIMCAZOLE; [3H]CFT ([3H]2-BETA-CARBOMETHOXY-3-BETA-(4-FLUORO-PHENYL)-TROPANE, [3H]WIN 35,428) ID BINDING-SITES; BRAIN AB Cocaine and several sigma receptor ligands inhibit dopamine uptake via a common site. This is evidenced by a concentration-dependent inhibition of dopamine uptake and displacement of the binding of [H-3]WIN 35,428 (also called CFT), a cocaine analog with high affinity for the dopamine transporter. Since several sigma receptor ligands have been shown to block the stimulant effects of cocaine, this site may serve as a target for future drug development to treat cocaine abuse. RP IZENWASSER, S (reprint author), NIDA,ADDICT RES CTR,PSYCHOBIOL SECT,POB 5180,BALTIMORE,MD 21224, USA. RI Izenwasser, Sari/G-9193-2012 NR 15 TC 41 Z9 43 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 19 PY 1993 VL 243 IS 2 BP 201 EP 205 DI 10.1016/0014-2999(93)90381-Q PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MD138 UT WOS:A1993MD13800014 PM 8276070 ER PT J AU CAWLEY, NX NOE, BD LOH, YP AF CAWLEY, NX NOE, BD LOH, YP TI PURIFIED YEAST ASPARTIC PROTEASE-3 CLEAVES ANGLERFISH PRO-SOMATOSTATIN-I AND PRO-SOMATOSTATIN-II AT DIBASIC AND MONOBASIC SITES TO GENERATE SOMATOSTATIN-14 AND SOMATOSTATIN-28 SO FEBS LETTERS LA English DT Article DE PRO-SOMATOSTATIN; YEAST; ASPARTIC PROTEASE; PROHORMONE PROCESSING; SOMATOSTATIN ID PROPEPTIDE CONVERTING ENZYME; PROHORMONE; IDENTIFICATION; ENDOPEPTIDASE; BIOSYNTHESIS; SEQUENCE; MEMBER; FAMILY AB Anglerfish somatostatin-14 (SS-14) and somatostatin-28 (aSS-28) are derived from pro-somatostatin I (aPSS-I) and pro-somatostatin II (PSS-II), respectively. Purified yeast aspartic protease 3 (YAP3), was shown to cleave aPSS-I at the Arg81-Lys82 to yield SS-14 and Lys-1SS-14. In contrast, YAP3 cleaved aPSS-II only at the monobasic residue, Arg73 to yield aSS-28. Since the paired basic and monobasic sites are present in both precursors, the results indicate that the structure and conformation of these substrates dictate where cleavage occurs. Furthermore, the data show that YAP3 has specificity for both monobasic and paired basic residues. C1 NICHHD,DEV NEUROBIOL LAB,CELLULAR NEUROBIOL SECT,BLDG 49,RM 5A38,BETHESDA,MD 20892. EMORY UNIV,SCH MED,DEPT ANAT & CELL BIOL,ATLANTA,GA 30322. UNIFORMED SERV UNIV HLTH SCI,DEPT BIOCHEM,BETHESDA,MD 20814. NR 23 TC 34 Z9 34 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 18 PY 1993 VL 332 IS 3 BP 273 EP 276 DI 10.1016/0014-5793(93)80648-E PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA MB755 UT WOS:A1993MB75500018 PM 8104828 ER PT J AU CHAMBLESS, LE MCMAHON, R FINCH, A SORLIE, P HEISS, G LYLES, R WU, KK AF CHAMBLESS, LE MCMAHON, R FINCH, A SORLIE, P HEISS, G LYLES, R WU, KK TI ARIC HEMOSTASIS STUDY .3. QUALITY-CONTROL SO THROMBOSIS AND HAEMOSTASIS LA English DT Article ID RISK FACTOR; LONG-TERM; VARIABILITY; FIBRINOGEN; CHOLESTEROL; DISEASE AB Methods and results from the quality assurance program of the Atherosclerosis Risk in Communities (ARIC) Study regarding hemostasis variables are presented, following up previous reports in this journal on standardized procedures for blood collection and processing (7) and-an organized plan for the performance of those procedures (8). Efforts were made to control for and assess all sources of variability, from venipuncture to laboratory analysis, including also local field center processing and sample shipping. The quality control program included (a) a standardized protocol for blood collection and processing; (b) training, certification, and annual recertification of field center personnel for blood collection and processing; (c) monitoring of fasting times, phlebotomy times, processing times, and shipping problems; (d) hemostatic laboratory internal quality control; (e) a replicate blood sample program; (f) an intraindividual variability study; and (g) continual monitoring of quality control and study participants' data. This paper focused on items (c), (d), and (e). Measures of variation, generally standard deviations and coefficients of variation, are estimated for replicate blood sampling and internal quality control data, for activated partial thromboplastin time, fibrinogen, factor VII and VIII activity, von Willebrand factor, antithrombin-III, and protein C. The results demonstrate that it is possible to reliably measure these hemostatic variables in a large multicenter study. C1 MARYLAND MED RES INST,BALTIMORE,MD. UNIV TEXAS,SCH MED,DIV HEMATOL ONCOL,HOUSTON,TX 77025. NHLBI,BETHESDA,MD 20892. UNIV N CAROLINA,SCH PUBL HLTH,DEPT EPIDEMIOL,CHAPEL HILL,NC 27514. RP CHAMBLESS, LE (reprint author), UNIV N CAROLINA,DEPT BIOSTAT,CHAPEL HILL,NC 27514, USA. RI Wu, Kenneth Kun-Yu/B-1070-2010 FU NHLBI NIH HHS [N01-HC-55018, N01-HC-55015, N01-HC-55016] NR 20 TC 19 Z9 19 U1 0 U2 1 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 OCT 18 PY 1993 VL 70 IS 4 BP 588 EP 594 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA MD218 UT WOS:A1993MD21800010 PM 8115984 ER PT J AU DIODATI, JG QUYYUMI, AA HUSSAIN, N KEEFER, LK AF DIODATI, JG QUYYUMI, AA HUSSAIN, N KEEFER, LK TI COMPLEXES OF NITRIC-OXIDE WITH NUCLEOPHILES AS AGENTS FOR THE CONTROLLED BIOLOGICAL RELEASE OF NITRIC-OXIDE - ANTIPLATELET EFFECT SO THROMBOSIS AND HAEMOSTASIS LA English DT Article ID RELAXING FACTOR; PLATELET-AGGREGATION; ENDOTHELIAL-CELLS; SMOOTH-MUSCLE; WHOLE-BLOOD; CYCLIC-GMP; SODIUM-NITROPRUSSIDE; INHIBITION; PROSTACYCLIN; ARTERY AB Nitric oxide (NO) inhibits platelet aggregation. Accordingly, we hypothesized that complexes of diethylamine and spermine with NO (DEA/NO and SPER/NO, respectively), two vasodilators previously shown to release NO spontaneously in aqueous solution, may also be useful antiplatelet agents. Platelet aggregation was measured in whole blood or platelet-rich plasma by impedance aggregometry after addition of collagen. In whole blood, the dose response curve for DEA/NO added 1 min before collagen was similar to that for aspirin (60% inhibition at 10(-4) M), while SPER/NO and sodium nitroprusside were less potent by an order of magnitude. In platelet-rich plasma, 10(-6) M DEA/NO caused 60% inhibition, while SPER/NO and sodium nitroprusside were as active only at 10(-5) M; aspirin's potency was unchanged from that in whole blood. In vivo, DEA/NO and sodium nitroprusside produced significant platelet inhibition 1 min after intravenous injection in the rabbit at 50 nmol/kg. Similar in vivo platelet inhibition was observed with SPER/NO and aspirin, but only at higher dose. The effects of DEA/NO and sodium nitroprusside were transient, lasting less than 30 min after treatment, while the activity of SPER/NO and aspirin was sustained throughout the 30 min experiment. The magnitude and duration of the antiplatelet effects of DEA/NO and SPER/NO correlate with the rates at which they release nitric oxide spontaneously in aqueous solution. Thus, NO/nucleophile complexes merit further exploration both as research tools and as potential antiplatelet agents. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,CHEM SECT,FREDERICK,MD 21701. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 49 TC 51 Z9 52 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 OCT 18 PY 1993 VL 70 IS 4 BP 654 EP 658 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA MD218 UT WOS:A1993MD21800021 PM 8115991 ER PT J AU LIU, SK ROBERTS, WC MARON, BJ AF LIU, SK ROBERTS, WC MARON, BJ TI COMPARISON OF MORPHOLOGIC FINDINGS IN SPONTANEOUSLY OCCURRING HYPERTROPHIC CARDIOMYOPATHY IN HUMANS, CATS AND DOGS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MUSCLE CELL DISORGANIZATION; LEFT-VENTRICULAR HYPERTROPHY; QUANTITATIVE-ANALYSIS; OBSTRUCTIVE CARDIOMYOPATHY; CLINICAL MANIFESTATIONS; PATHO-PHYSIOLOGY; DISEASE; INTERRELATIONS; FIBROSIS; THERAPY AB Morphologic features of spontaneously occurring hypertrophic cardiomyopathy (HC) were compared in 38 humans, 51 cats and 10 dogs. Asymmetric hypertrophy of the ventricular septum, marked disorganization ot cardiac muscle cells, abnormal intramural coronary arteries and myocardial fibrosis were each present in the ventricular septum of human, feline, and canine forms of HC; these abnormalities were generally more severe and most frequently identified in humans. Asymmetric left ventricular hypertrophy (based on the calculated septal-to-free wall thickness ratio) was most common in humans (31 of 38 [81%]) and dogs (8 of 10 [80%]), as compared with cats (16 of 51 [31%]; p <0.001) with HC; in all 3 species, hypertrophy was often diffuse, involving substantial portions of the anterolateral and posterior free walls, and the ventricular septum. Marked septal disorganization (greater-than-or-equal-to 5% of the tissue section) was present in 35 patients (92%), but on only 14 cats (27%) and 2 dogs (20%) (p <0.001). Abnormal intramural coronary arteries occurred with similar frequency in the ventricular septum of patients (n = 25; 66%), cats (n = 38; 74%) and dogs (n = 6; 60%) (p 9 muM had a significantly higher incidence of serious gastrointestinal and hematological toxicity. Compared to each patient's own baseline, a significant trend for decreasing ACTase activity with increasing PALA dose was evident using cytosol isolated from peripheral blood mononuclear cells 24 h after PALA treatment (P2 = 0.01). PALA less-than-or-equal-to 844 mg/m2 failed to appreciably inhibit ACTase activity at 24 h in most patients; furthermore, a decrease in ACTase activity by >50% from baseline was seen in only 29% of cycles. More consistent inhibition of ACTase activity was seen with PALA greater-than-or-equal-to 1266 mg/m2. Even with the highest PALA doses, however, ACTase activity returned to baseline by 96 h in most patients. In contrast, a modest decrease in plasma uridine levels was noted at all PALA doses, but the decrease was greater-than-or-equal-to 50% in only 21% of cycles at 24 h. PALA less-than-or-equal-to 1266 mg/m2 could be safely combined with a 72-h i.v. infusion of 5-FU 2000 mg/m2/day with LCV 500 mg/m2/day starting 24 h after PALA. Because the delivered 5-FU dose intensity for patients entered at or above 1750 mg/m2/day in this trial was similar at PALA doses less-than-or-equal-to 1266 mg/m2, we have selected 1266 mg/m2 for future studies. C1 NCI, CLIN ONCOL PROGRAM, BETHESDA, MD 20892 USA. NCI, DEV THERAPEUT PROGRAM, BETHESDA, MD 20892 USA. NCI, CANC THERAPY EVALUAT PROGRAM, BETHESDA, MD 20892 USA. NCI, DIV CANC TREATMENT, BETHESDA, MD 20892 USA. NIH, CTR CLIN, CANC NURSING SERV, BETHESDA, MD 20892 USA. NIH, CTR CLIN, DEPT PHARM, BETHESDA, MD 20892 USA. NR 52 TC 18 Z9 18 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 1993 VL 53 IS 20 BP 4828 EP 4836 PG 9 WC Oncology SC Oncology GA MB993 UT WOS:A1993MB99300020 PM 8402669 ER PT J AU SUPKO, JG BALCERZAK, SP KRAUT, EH AF SUPKO, JG BALCERZAK, SP KRAUT, EH TI PHASE-I EVALUATION AND PHARMACOKINETIC STUDY OF PYRAZINE-2-DIAZOHYDROXIDE ADMINISTERED AS A SINGLE BOLUS INTRAVENOUS-INJECTION IN PATIENTS WITH ADVANCED SOLID TUMORS SO CANCER RESEARCH LA English DT Article ID PYRAZINE DIAZOHYDROXIDE; CROSS-RESISTANCE; SODIUM-SALT; INVIVO; NSC-361456; STABILITY; TOXICITY; INVITRO; MODELS AB The sodium salt of pyrazine-2-diazohydroxide (PZDH; NSC 361456) was identified as an active congener of the antitumor lead pyridine-2-diazotate with enhanced chemical stability under physiological conditions. In a phase I trial of PZDH administered as a single i.v. bolus injection, 19 patients with refractory solid tumors received 44 courses of therapy at dose levels ranging from 50 to 350 mg/m2. No objective responses to PZDH were noted. Myelosuppression characterized by prolonged, delayed onset leukopenia and thrombocytopenia was the dose limiting toxicity. A maximum tolerated dose of 350 mg/m2 was identified for this treatment schedule. Nonhematological toxicity was limited to severe nausea and vomiting, experienced by all patients treated at the lower doses, although reasonably well controlled when antiemetics were given prior to chemotherapy. The plasma pharmacokinetics of PZDH was evaluated following a single course of therapy in 16 patients. Drug levels were monitored using a specific capillary gas chromatographic assay with a 1-ng/ml lower limit of quantitation. In patients treated with doses greater than 50 mg/m2, the concentration of PZDH in plasma declined in a distinctly triexponential manner and remained above 1.5 ng/ml for at least 8 h. However, the initial decay phase, characterized by a harmonic mean half-life of 3.9 +/- 3.5 (SD) min (range, 2.2-6.3 min), was the primary determinant of drug disposition, as indicated by its 85.5-93.1% contribution to the area under the plasma concentration-time profiles from time zero to infinity. The harmonic mean terminal half-life increased with escalations in dose from 2.7 +/- 0.8 h (n = 2) at 100 mg/m2 to 8.5 +/- 3.0 h at 350 mg/m2 (n = 6). Total plasma drug clearance was very similar in patients treated with doses of 50-250 mg/m2, exhibiting a mean value of 42.5 +/- 7.8 liters/h/m2 (n = 10); however, it was significantly lower at the 350 mg/m2 dose level, 27.2 +/- 6.6 liters/h/m2 (n = 6; P < 0.002), denoting a departure from linear pharmacokinetic behavior. The rather low steady state apparent volume of distribution, which ranged from 6.0 +/- 1.5 (50 mg/m2, n = 2) to 12.7 +/- 8.0 (350 mg/m2, n = 6) liters/m2, was indicative of limited distribution of the drug into body tissue. The absence of objective antitumor effects should not discourage continued evaluation of PZDH against solid tumors selected for probable sensitivity as indicated by preclinical testing. A dose of 250 mg/m2 on a single i.v. bolus schedule is recommended for these phase II trials. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. OHIO STATE UNIV,CTR COMPREHENS CANC,COLUMBUS,OH 43210. FU NCI NIH HHS [CA-09338, CA-16058, N01-CM-73701] NR 20 TC 5 Z9 5 U1 1 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 1993 VL 53 IS 20 BP 4843 EP 4849 PG 7 WC Oncology SC Oncology GA MB993 UT WOS:A1993MB99300022 PM 8402671 ER PT J AU BERLIN, O SAMID, D DONTHINENIRAO, R AKESON, W AMIEL, D WOODS, VL AF BERLIN, O SAMID, D DONTHINENIRAO, R AKESON, W AMIEL, D WOODS, VL TI DEVELOPMENT OF A NOVEL SPONTANEOUS METASTASIS MODEL OF HUMAN OSTEOSARCOMA TRANSPLANTED ORTHOTOPICALLY INTO BONE OF ATHYMIC MICE SO CANCER RESEARCH LA English DT Article ID HUMAN PROSTATIC-CARCINOMA; NUDE-MICE; DIFFERENT ORGANS; CELL-GROWTH; RAT; BEHAVIOR; THERAPY; INVIVO; TUMORS; SITES AB There is a pressing need for in vivo models in which potential antitumor agents can be tested for their ability to inhibit the growth and metastatic spread of human sarcomas. A recent advance in this regard has been the development of a v-Ki-ras-oncogene-transformed human osteosarcoma cell line (KRIB) that efficiently colonizes the lungs of athymic nude mice when cells (1 x 10(5)) are administered by i.v. injection. In the present study, we have utilized this cell line to develop a spontaneous metastasis model in which a small number of tumor cells are injected into the tibial bones of athymic mice. When as few as 1000 KRIB cells are orthotopically implanted into the tibial bones of nude mice, bone tumors, which are radio-graphically and histologically similar to primary human osteosarcoma, develop within 4 weeks. Furthermore, as in the human disease, cells from these primary tumors subsequently seed the animals' lungs, resulting in reproducible and quantifiable pulmonary metastasis evident both upon gross inspection of the lungs and histologically 6 weeks after tumor inoculation. Surgical amputation of the tumor inoculation site up to 2 weeks after tumor injection prevents pulmonary metastasis, indicating that substantial local (tibial) growth and invasion of the primary tumor for at least 2 weeks is required for subsequent metastasis. Implantation of s.c. 5000 KRIB cells fails to produce local or metastatic tumors. We anticipate that this model will prove to be a powerful tool with which to study the mechanisms of human osteosarcoma growth and pulmonary metastasis, and to assess the efficacy of promising therapeutic agents. C1 UNIV CALIF SAN DIEGO,MED CTR,DEPT ORTHOPAED,SAN DIEGO,CA 92103. UNIV CALIF SAN DIEGO,MED CTR,DEPT MED,SAN DIEGO,CA 92103. NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20829. FU NCI NIH HHS [CA 28896, CA 58527]; NHLBI NIH HHS [HL30480] NR 40 TC 88 Z9 93 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 1993 VL 53 IS 20 BP 4890 EP 4895 PG 6 WC Oncology SC Oncology GA MB993 UT WOS:A1993MB99300029 PM 8402677 ER PT J AU FURMANSKI, P HERMAN, CJ PADARATHSINGH, M AF FURMANSKI, P HERMAN, CJ PADARATHSINGH, M TI MOLECULAR MECHANISMS OF TUMOR-DEVELOPMENT AND PROGRESSION - NEW TARGETS FOR PREVENTION, DIAGNOSIS, AND THERAPY - A PATHOLOGY-B STUDY SECTION WORKSHOP - WORKING REPORT FROM THE DIVISION OF RESEARCH GRANTS, NATIONAL-INSTITUTES-OF-HEALTH SO CANCER RESEARCH LA English DT Editorial Material C1 NIH,DIV RES GRANTS,BETHESDA,MD 20892. NYU,DEPT BIOL,NEW YORK,NY 10003. GRADY MEM HOSP,DEPT ANAT PATHOL,ATLANTA,GA 30335. NR 0 TC 0 Z9 0 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 15 PY 1993 VL 53 IS 20 BP 5055 EP 5059 PG 5 WC Oncology SC Oncology GA MB993 UT WOS:A1993MB99300055 PM 8402698 ER PT J AU GOTLIEB, WH BRISTOL, LA WEISSMAN, AM DURUM, SK TAKACS, L AF GOTLIEB, WH BRISTOL, LA WEISSMAN, AM DURUM, SK TAKACS, L TI UP-REGULATION OF T-CELL RECEPTOR-GAMMA CHAIN TRANSCRIPTION BY INTERLEUKIN-2 SO CELLULAR IMMUNOLOGY LA English DT Article ID ANTIGEN RECEPTOR; FETAL THYMOCYTES; LYMPHOCYTES-T; RAT THYMOCYTES; IL-2 RECEPTORS; BEARING CELLS; DELTA-CHAIN; STEM-CELLS; ALPHA-BETA; GENE C1 NIAAA,PHYSIOL & PHARMACOL STUDIES,SPECIAL PROJECTS UNIT,ROCKVILLE,MD 20852. NCI,FREDERICK CANC RES FACIL,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS DEV PROGRAM,FREDERICK,MD 21701. NCI,BIOL RESPONSE MODIFIERS PROGRAM,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21701. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [N01 CO-74102] NR 60 TC 4 Z9 4 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD OCT 15 PY 1993 VL 151 IS 2 BP 345 EP 355 DI 10.1006/cimm.1993.1244 PG 11 WC Cell Biology; Immunology SC Cell Biology; Immunology GA MC136 UT WOS:A1993MC13600010 PM 8402941 ER PT J AU ABE, R KOZAK, CA FOOPHILLIPS, M ROBERTS, J PRINCIPATO, MAC AF ABE, R KOZAK, CA FOOPHILLIPS, M ROBERTS, J PRINCIPATO, MAC TI INVOLVEMENT OF MULTIPLE FACTORS IN THE CLONAL DELETION OF SELF-REACTIVE T-CELLS SO CELLULAR IMMUNOLOGY LA English DT Article ID MAMMARY-TUMOR VIRUS; MAJOR HISTOCOMPATIBILITY COMPLEX; LONG TERMINAL REPEAT; OPEN READING FRAME; MHC GENE-PRODUCTS; I-E; NEGATIVE SELECTION; IMPARTS REACTIVITY; MLS SYSTEM; MOUSE C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,NAVAL MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20814. UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814. US FDA,IMMUNOBIOL BRANCH,DIV VIRULENCE ASSESSMENT,LAUREL,MD 20708. RP ABE, R (reprint author), NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892, USA. NR 53 TC 0 Z9 0 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD OCT 15 PY 1993 VL 151 IS 2 BP 425 EP 436 DI 10.1006/cimm.1993.1251 PG 12 WC Cell Biology; Immunology SC Cell Biology; Immunology GA MC136 UT WOS:A1993MC13600017 PM 7691421 ER PT J AU LIPSKA, BK WEINBERGER, DR AF LIPSKA, BK WEINBERGER, DR TI DELAYED-EFFECTS OF NEONATAL HIPPOCAMPAL DAMAGE ON HALOPERIDOL-INDUCED CATALEPSY AND APOMORPHINE-INDUCED STEREOTYPIC BEHAVIORS IN THE RAT SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE NEONATAL LESION; HIPPOCAMPUS; IBOTENIC ACID; STEREOTYPY; CATALEPSY; APOMORPHINE; HALOPERIDOL; DOPAMINE ID MEDIAL PREFRONTAL CORTEX; IBOTENIC ACID LESIONS; NUCLEUS-ACCUMBENS-SEPTI; VENTRAL TEGMENTAL AREA; LOCOMOTOR-ACTIVITY; MESOLIMBIC DOPAMINE; FRONTAL-CORTEX; ANTEROGRADE TRANSPORT; DIRECT PROJECTION; AMMONS HORN AB The developmental effects of neonatal excitotoxic ventral hippocampal (VH) damage on behaviors related to dopaminergic (DA) transmission in the basal ganglia were investigated in the rat. Ibotenic acid (in Lesion) or artificial cerebrospinal fluid (in Sham) was infused into the VH of 7-day-old (PD7) rat pups. Haloperidol-induced (1 mg/kg, i.p.) catalepsy and apomorphine-induced (0.75 mg/kg, s.c.) stereotypic behaviors as well as locomotion were assessed in Sham and Lesion rats prior to (PD35) and after puberty (PD56). On PD35, Lesion and Sham animals did not differ in induced catalepsy or stereotypy. On PD56, however, Lesion animals were less cataleptic following haloperidol injection and manifested supersensitivity to apomorphine as compared to Sham rats. At both, PD35 and PD56, locomotor activity after apomorphine was significantly increased in Lesion animals as compared with controls. These results indicate that the neonatal excitotoxic VH lesion results in a unique time-dependent pattern of behavioral changes related to striatal DA transmission. Moreover, the response to apomorphine differs qualitatively from that previously reported after the analogous lesion induced in adult animals in which stereotypy was reduced. These findings suggest that early hippocampal deefferentation affects the development of other brain regions, such as the medial prefrontal cortex, that are also involved in the regulation of striatal DA function. C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH,INTRAMURAL RES PROGRAM,WASHINGTON,DC 20032. RI Lipska, Barbara/E-4569-2017 NR 88 TC 134 Z9 137 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD OCT 15 PY 1993 VL 75 IS 2 BP 213 EP 222 DI 10.1016/0165-3806(93)90026-7 PG 10 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA MB433 UT WOS:A1993MB43300008 PM 7903225 ER PT J AU TOMAREV, SI ZINOVIEVA, RD WEIS, VM CHEPELINSKY, AB PIATIGORSKY, J MCFALLNGAI, MJ AF TOMAREV, SI ZINOVIEVA, RD WEIS, VM CHEPELINSKY, AB PIATIGORSKY, J MCFALLNGAI, MJ TI ABUNDANT MESSENGER-RNAS IN THE SQUID LIGHT ORGAN ENCODE PROTEINS WITH A HIGH SIMILARITY TO MAMMALIAN PEROXIDASES SO GENE LA English DT Article DE MYELOPEROXIDASE; SYMBIOSIS; OXIDATIVE STRESS; LENS; EUPRYMNA SCOLOPES; CRYSTALLIN; ALDEHYDE DEHYDROGENASE ID HUMAN EOSINOPHIL PEROXIDASE; ANIMAL-BACTERIAL MUTUALISM; HUMAN MYELOPEROXIDASE; THYROID PEROXIDASE; EUPRYMNA-SCOLOPES; MOLECULAR-CLONING; LENS CRYSTALLINS; CHROMOSOMAL GENE; MESSENGER-RNAS; SEQUENCE AB A library derived from mRNA in the bacterial light organ of the squid, Euprymna scolopes, contained an unexpectedly high proportion of cDNAs that encode proteins with approximately 30% similarity to a family of mammalian peroxidases (PO) including myelo-PO, eosinophil PO, and thyroid PO (donor:hydrogen-peroxide oxidoreductase; EC 1.11.1.7). Two nearly fun-length cDNAs were determined to encode putative PO of nearly 93 kDa each that are 97% identical in amino acid sequence to each other. Each contains four potential glycosylation sites, and His(416), believed to be within the active site of the human PO, is conserved in the putative PO from the squid light organ. The mRNAs for the putative squid PO were approximately 250 times more abundant in the tissue housing the bacterial symbiont than in the ocular lens or mantle and were undetectable in the light organ lens. By analogy with the bacteriocidal function of PO in mammalian neutrophils, the putative squid PO may be important for modulating or limiting the population of bacteria within the light organ. The possibility that the squid light organ contains a high concentration of PO raises the possibility that the light organ lens is under oxidative stress, providing a possible rationale for the recruitment of its aldehyde dehydrogenase-like crystallin. C1 UNIV SO CALIF,DEPT BIOL SCI,LOS ANGELES,CA 90089. RP TOMAREV, SI (reprint author), NEI,MOLEC & DEV BIOL LAB,BLDG 6,ROOM 203,BETHESDA,MD 20892, USA. NR 33 TC 31 Z9 31 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD OCT 15 PY 1993 VL 132 IS 2 BP 219 EP 226 DI 10.1016/0378-1119(93)90199-D PG 8 WC Genetics & Heredity SC Genetics & Heredity GA MC879 UT WOS:A1993MC87900009 PM 8224867 ER PT J AU SHELLY, LL LEI, KJ PAN, CJ SAKATA, SF RUPPERT, S SCHUTZ, G CHOU, JY AF SHELLY, LL LEI, KJ PAN, CJ SAKATA, SF RUPPERT, S SCHUTZ, G CHOU, JY TI ISOLATION OF THE GENE FOR MURINE GLUCOSE-6-PHOSPHATASE, THE ENZYME-DEFICIENT IN GLYCOGEN-STORAGE-DISEASE TYPE-1A SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID HEPATIC-MICROSOMAL GLUCOSE-6-PHOSPHATASE; MULTIFUNCTIONAL GLUCOSE-6-PHOSPHATASE; SYSTEM; LIVER; IDENTIFICATION; PROTEINS AB Glycogen storage disease (GSD) type 1a (von Gierke disease) is caused by a deficiency in glucose-6-phosphatase, the key enzyme in glucose homeostasis catalyzing the terminal step in gluconeogenesis and glycogenolysis. Despite its clinical importance, this membrane-bound enzyme has eluded molecular characterization. Here we report the cloning and characterization of a murine glucose-6-phosphatase cDNA by screening a mouse liver cDNA library differentially with mRNA populations representing the normal and the albino deletion mouse known to express markedly reduced glucose-6-phosphatase activity. Additionally, we identified the gene that consists of 5 exons. Biochemical analyses indicate that the in vitro expressed enzyme is indistinguishable from mouse liver microsomal glucose-6-phosphatase exhibiting essentially identical kinetic constants, latency, thermal lability, and vanadate sensitivity. The characterization of the murine glucose-6-phosphatase gene opens the way for studying the molecular basis of GSD type 1a in humans and its etiology in an animal model. C1 NICHHD,HUMAN GENET BRANCH,BLDG 10,RM 95242,BETHESDA,MD 20892. GERMAN CANC RES CTR,INST CELL & TUMOR BIOL,W-6900 HEIDELBERG,GERMANY. NR 29 TC 129 Z9 133 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 15 PY 1993 VL 268 IS 29 BP 21482 EP 21485 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MC809 UT WOS:A1993MC80900008 PM 8407995 ER PT J AU BIRD, GS PUTNEY, JW AF BIRD, GS PUTNEY, JW TI INHIBITION OF THAPSIGARGIN-INDUCED CALCIUM-ENTRY BY MICROINJECTED GUANINE-NUCLEOTIDE ANALOGS - EVIDENCE FOR THE INVOLVEMENT OF A SMALL G-PROTEIN IN CAPACITATIVE CALCIUM-ENTRY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID LACRIMAL ACINAR-CELLS; RAT-LIVER MICROSOMES; CA-2+ RELEASE; INOSITOL TRISPHOSPHATE; INTRACELLULAR CALCIUM; GTP; POOLS; STIMULATION AB Injection of mouse lacrimal acinar cells with the non-hydrolyzable analogue of GTP, GTPgammaS (guanosine 5'-3-O-(thio)triphosphate), caused a rapid release of intracellular calcium but failed to activate calcium entry. Injection of GTPgammaS together with the inositol 1,4,5-trisphosphate receptor inhibitor, heparin, did not induce calcium release but blocked the activation of capacitative calcium entry by thapsigargin. Injection of GDPbetaS (guanosine 5'-O-(thio)diphosphate) produced similar effects. The inhibitory effects of GDPbetaS were prevented if an equal concentration of GTP was included in the injection pipette. These findings suggest that one of the steps linking the depletion of intracellular calcium pools to calcium entry across the plasma membrane requires the hydrolysis of GTP and may involve a small G-protein. RP BIRD, GS (reprint author), NIEHS,CELLULAR & MOLEC PHARMACOL LAB,CALCIUM REGULAT SECT,RES TRIANGLE PK,NC 27709, USA. NR 23 TC 182 Z9 183 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 15 PY 1993 VL 268 IS 29 BP 21486 EP 21488 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MC809 UT WOS:A1993MC80900009 PM 8407996 ER PT J AU HOMOLYA, L HOLLO, Z GERMANN, UA PASTAN, I GOTTESMAN, MM SARKADI, B AF HOMOLYA, L HOLLO, Z GERMANN, UA PASTAN, I GOTTESMAN, MM SARKADI, B TI FLUORESCENT CELLULAR INDICATORS ARE EXTRUDED BY THE MULTIDRUG-RESISTANCE PROTEIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID P-GLYCOPROTEIN; INSECT CELLS; TRANSPORTER; VINBLASTINE; EXPRESSION; CDNA; DYES AB In this report we show that NIH-3T3 mouse fibroblasts stably expressing the human multidrug transporter (MDR1 or P-glycoprotein), in contrast to the control NIH-3T3 cells, actively extrude the hydrophobic acetoxymethyl ester (AM) derivatives used for cellular loading of various fluorescent calcium and pH indicators. This dye extrusion is blocked by competing substrates and inhibitors of the multidrug transporter, e.g. by verapamil, vincristine, sodium orthovanadate, oligomycin, and a monoclonal anti-MDR1 antibody. The hydrophilic free acid forms of the indicators are not exported by MDR1. We also demonstrate that in isolated cell membranes the MDR1-ATPase, similar to that by known substrates of the transporter, is stimulated by the AM derivatives of fluorescent dyes whereas the free acid forms of the dyes are without effect. Since (i) the AM derivatives of the fluorescent indicators rapidly permeate the cell membrane and are readily cleaved by high activity and large capacity cytoplasmic esterases and (ii) the free acid forms are not substrates for export by MDR1, the observations above suggest that dye extrusion by MDR1 may occur without a cytoplasmic appearance of the AM compounds. These data also call attention to the possible interaction of widely used hydrophobic fluorescent indicators with MDR1 and offer an efficient detection of MDR1-expressing tumor cells as well as a screening method for examining drug interactions with the multidrug transporter. C1 NATL INST HAEMATOL BLOOD TRANSFUS & IMMUNOL,DAROCZI U 24,H-1113 BUDAPEST,HUNGARY. NCI,BETHESDA,MD 20892. RI Sarkadi, Balazs/I-5024-2013; Homolya, Laszlo/N-1154-2016 NR 24 TC 411 Z9 419 U1 0 U2 13 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 15 PY 1993 VL 268 IS 29 BP 21493 EP 21496 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MC809 UT WOS:A1993MC80900011 PM 8104940 ER PT J AU OSHIRO, S NAKAJIMA, H MARKELLO, T KRASNEWICH, D BERNARDINI, I GAHL, WA AF OSHIRO, S NAKAJIMA, H MARKELLO, T KRASNEWICH, D BERNARDINI, I GAHL, WA TI REDOX, TRANSFERRIN-INDEPENDENT, AND RECEPTOR-MEDIATED ENDOCYTOSIS IRON UPTAKE SYSTEMS IN CULTURED HUMAN FIBROBLASTS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ISOLATED RAT HEPATOCYTES; PLASMA-MEMBRANE; DIFERRIC TRANSFERRIN; K562 CELLS; BOUND IRON; REDUCTASE; LIVER; MECHANISM; RETICULOCYTES; LYSOSOMES AB Sepharose beads bound to Fe-55-transferrin (Tf) were used to evaluate Tf-dependent iron uptake not employing receptor-mediated endocytosis (RME). The iron of Fe-55(2)-Tf-Sepharose was reduced and taken up by cultured human fibroblasts in a time- and concentration-dependent fashion (K(m) 7 muM; V(max) 128 pmol/mg/min). This redox system resembled that for Tf-independent iron uptake (Tf-IU, evaluated using Fe-55-citrate) in several ways. 1) NH4Cl did not inhibit iron uptake from Fe-55-citrate and Fe-55(2)-Tf-Sepharose but did inhibit uptake from Fe-55(2)-Tf (RME system). 2) Iron uptake and reduction from Fe-55(2)-Tf-Sepharose and Fe-55-citrate increased with temperature hyperbolically, differing from the sigmoidal curve for RME uptake. 3) The subcellular distributions of iron from Fe-55-citrate and Fe-55(2)-Tf-Sepharose resembled each other and differed from that for Fe-55(2)-Tf. 4) The optimal pH for iron reduction and uptake using Fe-55(2)-Tf-Sepharose or Fe-55-citrate was less than pH 5.5, while that for iron uptake from Fe-55(2)-Tf was pH 7.4. 5) The uptake and reduction of iron from Fe-55(2)-Tf-Sepharose was inhibited by ferric citrate and by transition metals. We conclude that both Tf-independent and non-RME, Tf-dependent iron uptake proceed via a common redox system for iron. The mechanisms of cellular iron uptake can be separately evaluated in fibroblasts using Fe-55-citrate, Fe-55(2)-Tf, and Fe-55(2)-Tf-Sepharose beads. C1 NICHHD,HUMAN GENET BRANCH,HUMAN BIOCHEM GENET SECT,BLDG 10,RM 95242,BETHESDA,MD 20892. TOKYO MED & DENT UNIV,MED RES INST,DEPT BIOCHEM GENET,TOKYO 113,JAPAN. NR 43 TC 47 Z9 47 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 15 PY 1993 VL 268 IS 29 BP 21586 EP 21591 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MC809 UT WOS:A1993MC80900026 PM 8408010 ER PT J AU ZDANOVSKY, AG CHIRON, M PASTAN, I FITZGERALD, DJ AF ZDANOVSKY, AG CHIRON, M PASTAN, I FITZGERALD, DJ TI MECHANISM OF ACTION OF PSEUDOMONAS EXOTOXIN - IDENTIFICATION OF A RATE-LIMITING STEP SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALPHA-2-MACROGLOBULIN RECEPTOR; LIPOPROTEIN RECEPTOR; CELLULAR PROTEASE; DIPHTHERIA-TOXIN; ESCHERICHIA-COLI; AERUGINOSA; SITE; GLYCOPROTEIN; CYTOTOXICITY; MUTAGENESIS AB Pseudomonas exotoxin (PE) enters cells by receptor-mediated endocytosis and is cleaved by a cellular protease between Arg279 and Gly280 to produce an NH2-terminal fragment of 28 kDa which contains the toxin's binding domain and a COOH-terminal fragment of 37 kDa which has translocating and ADP-ribosylating activity. After proteolysis, the COOH-terminal fragment reaches the endoplasmic reticulum by retrograde transport where it translocates to the cytosol and inhibits protein synthesis by ADP-ribosylating elongation factor 2. To understand how the 37-kDa fragment functions, we focused on the role of specific amino acids located near its NH2 terminus. We found that there was a 4-250-fold loss in toxic activity when tryptophan 281, leucine 284, or tyrosine 289 were changed to other residues. Mutations at these three positions did not interfere with the receptor binding, cell-mediated proteolytic cleavage, or ADP-ribosylating activity. To determine the role of these amino acids, a competition assay was devised in which the addition of excess PEDELTA553, a mutant form of PE that lacks ADP-ribosylation activity, competed efficiently for the toxicity of PE. Excess PE with mutations near the NH2 terminus of the 37-kDa fragment competed poorly. This competition occurred after proteolysis since PEGly276, a mutant form of PE that is not cleaved, did not compete. We conclude that specific amino acids at the NH2 terminus of the 37-kDa fragment interact in a saturable manner with an unknown intracellular component. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 22 TC 29 Z9 30 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 15 PY 1993 VL 268 IS 29 BP 21791 EP 21799 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MC809 UT WOS:A1993MC80900057 PM 8408034 ER PT J AU CHEN, HW CHAN, WY CHEN, CL MANSFIELD, BC CHOU, JY AF CHEN, HW CHAN, WY CHEN, CL MANSFIELD, BC CHOU, JY TI THE CARBOXYL-TERMINAL DOMAIN OF THE HUMAN PREGNANCY-SPECIFIC GLYCOPROTEIN SPECIFIES INTRACELLULAR RETENTION AND STABILITY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN CARCINOEMBRYONIC ANTIGEN; INTERCELLULAR-ADHESION MOLECULE; ENDOPLASMIC-RETICULUM; GENE FAMILY; MESSENGER-RNAS; CDNA SEQUENCE; CELL-ADHESION; BREFELDIN-A; BETA-1-GLYCOPROTEIN; PROTEINS AB The pregnancy-specific glycoproteins (PSGs), which are members of the immunoglobulin superfamily, are the major pregnancy-associated proteins synthesized by the human placenta. Thirty or more PSG members have been identified which are encoded by at least 11 linked genes. The PSG proteins share 85-95% sequence homology in the coding region, but show variability at the carboxyl-terminal (COOH) domains. In the present study, we examined the effects of PSG COOH domains on protein secretion and stability. Using PSGs containing short (11-12 residues) hydrophilic (PSG1e, PSG11s, and PSG16a), short (22 residues) hydrophobic (PSG6r), and long (81 residues) hydrophobic (PSG11w) COOH domains, we showed that most PSG members were secretory proteins except PSG11w which was largely retained in cells. When the PSG11w COOH domain was replaced with a short COOH domain of PSG1e, the resulting PSG-N11w/C1e chimera became secreted into the medium. On the other hand, chimeras that harbored the PSG11w COOH domain, PSG-N1e/C11w and PSG-N16a/C11w, remained in cells, demonstrating that the COOH domain of PSG11w confers intracellular retention. Deletion analysis showed that mutant (PSG11w-C2) that contained the first 21 amino acids of PSG11w COOH domain or mutant (PSG11w-C3) that contained a deletion of hydrophobic residues 372-392 in the PSG11w COOH domain remained largely in cells. In contrast, the PSG11w-C1 mutant which contained the first 12 residues of the PSG11w COOH domain became a secretory protein. Studies of PSG synthesis and processing in the presence of Brefeldin A, a drug that impedes protein transport from endoplasmic reticulum to the Golgi system, showed that PSG11w resided and degraded in the endoplasmic reticulum. The endoplasmic reticulum localization of PSG11w and the cell-associated mutant PSGs was further demonstrated by their sensitivity to endoglycosidase H and indirect immunofluorescence analysis. C1 NICHHD,HUMAN GENET BRANCH,BLDG 10,RM 95242,BETHESDA,MD 20892. UNIV FLORIDA,COLL VET MED,DEPT LARGE ANIM CLIN SCI,GAINESVILLE,FL 32611. GEORGETOWN UNIV,MED CTR,DEPT PEDIAT,WASHINGTON,DC 20007. MASSEY UNIV,DEPT MICROBIOL & GENET,PALMERSTON NORTH,NEW ZEALAND. NR 59 TC 4 Z9 4 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 15 PY 1993 VL 268 IS 29 BP 22066 EP 22075 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MC809 UT WOS:A1993MC80900094 PM 8408064 ER PT J AU MERCHENTHALER, I LIPOSITS, Z REID, JJ WETSEL, WC AF MERCHENTHALER, I LIPOSITS, Z REID, JJ WETSEL, WC TI LIGHT AND ELECTRON-MICROSCOPIC IMMUNOCYTOCHEMICAL LOCALIZATION OF PKC-DELTA IMMUNOREACTIVITY IN THE RAT CENTRAL-NERVOUS-SYSTEM SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE SIGNAL TRANSDUCTION; 2ND MESSENGERS; BRAIN; IMMUNOCYTOCHEMISTRY ID PROTEIN-KINASE-C; PHORBOL ESTER; DIFFERENTIAL EXPRESSION; MESSENGER-RNAS; BRAIN; ACTIVATION; FAMILY; ISOZYMES; MEMBER; TISSUE AB Protein kinase C (PKC) is one of the major cellular signal transduction systems. Since at least nine different PKC isoenzymes have been described, the purpose of the present studies was to identify the regional, cellular, and subcellular distributions of PKCdelta in the rat central nervous system (CNS) by light and electron microscopic immunocytochemistry. We have found that PKCdelta immunoreactivity is present in all major subdivisions of the rat CNS. Within each of the subdivisions, PKCdelta immunoreactivity is localized to perikarya that monitor sensory and motor functions. More specifically, PKCdelta is found in the olfactory bulb, cerebral cortex, lateral septum, thalamus, vestibular and cochlear nuclei, inferior olive, nucleus of the solitary tract, cerebellum, and superficial layers of the dorsal horn in the spinal cord. In most cases, the distribution of this isoenzyme is distinct from that of the conventional isoforms. Within the CNS, PKCdelta is localized primarily in neurons; however, neurons of the same type are not uniformly labeled. This is most evident in the cerebellum, where alternating columns of Purkinje cells are immunostained. While PKCdelta is prominent in perikarya, occasional immunostaining is seen in dendrites, fibers or axons, and nerve terminals. Electron microscopic analysis of the posterolateral nucleus of the thalamus reveals that the cell nucleus, the rough endoplasmic reticulum, and the plasma membrane are all immunopositive. Since each of the PKC subspecies may have different substrate, lipid, and other co-factor requirements, the regional, cellular, and subcellular distribution of each of these isoforms should help to define their functional environments. (C) 1993 Wiley-Liss, Inc. C1 NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,REPROD NEUROENDOCRINOL SECT,RES TRIANGLE PK,NC 27709. RP MERCHENTHALER, I (reprint author), NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,FUNCT MORPHOL SECT,MD C4-07,RES TRIANGLE PK,NC 27709, USA. NR 56 TC 36 Z9 36 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD OCT 15 PY 1993 VL 336 IS 3 BP 378 EP 399 DI 10.1002/cne.903360306 PG 22 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA LZ648 UT WOS:A1993LZ64800005 PM 8263228 ER PT J AU KOZLOWSKI, S CORR, M SHIRAI, M BOYD, LF PENDLETON, CD BERZOFSKY, JA MARGULIES, DH AF KOZLOWSKI, S CORR, M SHIRAI, M BOYD, LF PENDLETON, CD BERZOFSKY, JA MARGULIES, DH TI MULTIPLE PATHWAYS ARE INVOLVED IN THE EXTRACELLULAR PROCESSING OF MHC CLASS-I-RESTRICTED PEPTIDES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HISTOCOMPATIBILITY COMPLEX-MOLECULES; TOXIC LYMPHOCYTES-T; SOLUBLE-PROTEIN; INFLUENZA NUCLEOPROTEIN; ANTIGEN PRESENTATION; SYNTHETIC PEPTIDES; CONVERTING ENZYME; CELL HYBRIDOMAS; VIRUS ENVELOPE; RECOGNITION AB T cell stimulation by certain class I-restricted antigenic peptides, such as the HIV 1 gp160-derived peptide, P18, requires peptide processing by angiotensin-1 converting enzyme (ACE) in FCS. We observed that longer versions of P18 and the murine cytomegalovirus pp89-derived core peptide, pMCMV, which could stimulate T cell hybridomas in FCS, were not as sensitive to the ACE inhibitor captopril as P18. Using cell-free soluble murine class I MHC molecules and protease inhibitors, we found that there are pathways of differing efficiency that use enzymes other than ACE for the proteolytic processing of peptides in serum. The kinetics of the generation of T cell stimulatory activity among P18 variant peptides in serum differed with peptide length, and with the nature of amino and COOH-terminal extensions. Such processing occurs in human plasma as well as in FCS. The understanding of this processing, its kinetics, and its inhibitors can lead to better design of peptide-based therapies, including vaccines. C1 NIAID,MOLEC BIOL SECT,IMMUNOL LAB,BLDG 10,ROOM 11N311,BETHESDA,MD 20892. NCI,MOLEC IMMUNOGENET & VACCINE RES SECT,METAB BRANCH,BETHESDA,MD 20892. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 50 TC 51 Z9 51 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 1993 VL 151 IS 8 BP 4033 EP 4044 PG 12 WC Immunology SC Immunology GA MB163 UT WOS:A1993MB16300010 PM 8409383 ER PT J AU PALIOGIANNI, F AHUJA, SS BALOW, JP BALOW, JE BOUMPAS, DT AF PALIOGIANNI, F AHUJA, SS BALOW, JP BALOW, JE BOUMPAS, DT TI NOVEL MECHANISM FOR INHIBITION OF HUMAN T-CELLS BY GLUCOCORTICOIDS - GLUCOCORTICOIDS INHIBIT SIGNAL-TRANSDUCTION THROUGH IL-2 RECEPTOR SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RETINOBLASTOMA-SUSCEPTIBILITY-GENE; PROTEIN KINASE-C; NF-KAPPA-B; TYROSINE PHOSPHORYLATION; NUCLEAR TRANSCRIPTION; HUMAN INTERLEUKIN-2; LYMPHOCYTES-T; GROWTH-FACTOR; ACTIVATION; PROLIFERATION AB Interaction of IL-2 with its high affinity membrane receptor complex (IL-2R) present on activated T lymphocytes induces cell proliferation and mediates effector functions. Glucocorticoids inhibit IL-2 production by inhibiting TCR-mediated signal transduction. We asked whether they also inhibit the action of IL-2 by inhibiting signal transduction through IL-2R. Human peripheral blood T cells, stimulated with PMA for 48 h (PMA blasts), were incubated with IL-2 in the presence of incremental dosages of dexamethasone (Dex; 10(-5)-10(-9)M). Dex inhibited the IL-2-dependent proliferation of PMA blasts in a dose-dependent fashion (IC50, 5 X 10(-8)M). Cell surface expression of IL-2R alpha- and beta-chains as determined by immunofluorence analysis was not affected by Dex. In addition, Scatchard plot analysis of I-125-labeled IL-2 showed that Dex did not affect the binding of IL-2, thus suggesting that inhibition is due to a postreceptor effect. Inhibition of T cell proliferation by Dex was associated with decreased IL-2-dependent tyrosine phosphorylation of several intracellular proteins and decreased phosphorylation of the retinoblastoma gene product Rb, a protein essential for controlling the progression of cells through the cell cycle. IL-2-dependent IL-2Ralpha expression in PMA blasts and NF-kB induction in resting human T cells were also inhibited by Dex. These results demonstrate that glucocorticoids inhibit preactivated T cells by down-regulating signal transduction through IL-2R. RP PALIOGIANNI, F (reprint author), NIDDKD,KIDNEY DIS SECT,BLDG 10,RM 3N114,BETHESDA,MD 20892, USA. NR 41 TC 107 Z9 111 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 1993 VL 151 IS 8 BP 4081 EP 4089 PG 9 WC Immunology SC Immunology GA MB163 UT WOS:A1993MB16300014 PM 8409387 ER PT J AU SIEGEL, JN JUNE, CH YAMADA, H RAPP, UR SAMELSON, LE AF SIEGEL, JN JUNE, CH YAMADA, H RAPP, UR SAMELSON, LE TI RAPID ACTIVATION OF C-RAF-1 AFTER STIMULATION OF THE T-CELL RECEPTOR OR THE MUSCARINIC RECEPTOR TYPE-1 IN RESTING T-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASE; ANTIGEN RECEPTOR; SIGNAL TRANSDUCTION; MAP KINASE; RAF-1 KINASE; ZETA-CHAIN; MONOCLONAL-ANTIBODY; PHOSPHATASE CD45; PHOSPHORYLATION; INTERLEUKIN-2 AB The c-Raf-1 serine/threonine kinase is an important component of signal transduction pathways mediating the effects of a variety of growth factors. In activated T cells, IL-2 has been shown to induce activation of c-Raf-1, but c-Raf-1 has not previously been shown to be activated through the T-cell receptor (TCR) in resting G0 T cells. Using a sensitive immune complex kinase reaction, we show that cross-linking of the stimulatory and costimulatory receptors CD3, CD4, or CD28 induces c-Raf-1 activation in highly purified resting peripheral blood human T cells. In contrast, cross-linking the nonstimulatory receptor CD45 did not induce c-Raf-1. Surprisingly, although earlier studies had shown delayed kinetics in response to Thy-1 stimulation in murine cells, c-Raf-1 activation in response to CD3 cross-linking was one of the earliest measurable events. In spite of its early kinetics, c-Raf-1 activation was found to be downstream of several other early signal transduction events, including activation of a tyrosine kinase and a tyrosine phosphatase. Several lines of evidence suggest that activation of c-Raf-1 in response to TCR stimulation may be PKC-dependent: first, phorbol esters are extremely potent activators of c-Raf-1 in human T cells; second, the kinetics of accumulation of products of phosphatidylinositol hydrolysis coincides with the kinetics of c-Raf-1 activation; and third, physiologic activation of the PLC/PKC pathway through a transfected, G-protein-coupled receptor HM1 induced similar levels of c-Raf-1 activation with a similar time course. We conclude that c-Raf-1 activation is tightly coupled to TCR stimulation and may participate in signal transduction pathways in resting, G0 T cells. The observation that the HM1 receptor can also activate c-Raf-1 suggests that T cells have the capability to utilize both tyrosine kinase-dependent and tyrosine kinase-independent mechanisms of c-Raf-1 activation. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. RP SIEGEL, JN (reprint author), USN,INST MED RES,IMMUNE CELL BIOL PROGRAM,MAIL STOP 6,BETHESDA,MD 20889, USA. NR 64 TC 45 Z9 45 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 1993 VL 151 IS 8 BP 4116 EP 4127 PG 12 WC Immunology SC Immunology GA MB163 UT WOS:A1993MB16300018 PM 8409389 ER PT J AU ALLEN, JB WONG, HL COSTA, GL BIENKOWSKI, MJ WAHL, SM AF ALLEN, JB WONG, HL COSTA, GL BIENKOWSKI, MJ WAHL, SM TI SUPPRESSION OF MONOCYTE FUNCTION AND DIFFERENTIAL REGULATION OF IL-1 AND IL-1RA BY IL-4 CONTRIBUTE TO RESOLUTION OF EXPERIMENTAL ARTHRITIS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERLEUKIN-1 RECEPTOR ANTAGONIST; NECROSIS FACTOR-ALPHA; CD4+ T-CELLS; GENE-EXPRESSION; RECOMBINANT IL-4; INVITRO; MACROPHAGES; PROSTAGLANDIN-E2; INHIBITION; SECRETION AB IL-4 has diverse effects on hematopoietic cells, including the ability to suppress certain mononuclear cell functions. To evaluate the effect of IL-4 on the evolution of acute and chronic arthritis, murine recombinant IL-4 was administered systemically to animals receiving an arthropathic dose of group A streptococcal cell wall fragments. Daily treatment with IL-4 had a minimal effect on the acute phase, but significantly suppressed the chronic, destructive phase. By 4 wk after initiation of disease, the articular index of IL-4-treated animals was reduced >60% (articular index = 4 +/- 0.9) compared with the untreated rats (11.5 +/- 0.48, p < 0.001). A substantial decrease in the influx of inflammatory cells and virtual elimination of pannus and erosions occurred after IL-4 therapy. Associated with the reduced accumulation of mononuclear leukocytes was a decrease in their proinflammatory functions including cytokine production and reactive oxygen intermediate metabolism. These observations are consistent with the selective effects of IL-4 on phagocytic cell function demonstrated in vitro. Furthermore, IL-4 induced gene expression for IL-1ra, a protein that antagonizes the action of IL-1 by binding to the IL-1 receptor without agonist activity. Through an expanding spectrum of effects on monocyte-macrophage phenotypic and functional parameters, IL-4 is emerging as an important inhibitor of cell-mediated immune responses and pathogenic processes. C1 NIDR,CELLULAR IMMUNOL SECT,IMMUNOL LAB,BLDG 30,ROOM 331,BETHESDA,MD 20892. UPJOHN CO,KALAMAZOO,MI 49007. NR 47 TC 159 Z9 160 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 1993 VL 151 IS 8 BP 4344 EP 4351 PG 8 WC Immunology SC Immunology GA MB163 UT WOS:A1993MB16300042 PM 8409406 ER PT J AU TAITELBAUM, H FERRETTI, JA SPENCER, RGS WEISS, GH AF TAITELBAUM, H FERRETTI, JA SPENCER, RGS WEISS, GH TI 2-STAGE INVERSION-RECOVERY EXPERIMENTS FOR MEASUREMENTS OF T1 SO JOURNAL OF MAGNETIC RESONANCE SERIES A LA English DT Article ID NMR-SPECTROSCOPY; RELAXATION; DYNAMICS C1 NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. NIA,CELLULAR & MOLEC BIOL LAB,BALTIMORE,MD 21224. UNIV MARYLAND,INST PHYS SCI & TECHNOL,COLL PK,MD 20742. RP TAITELBAUM, H (reprint author), NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892, USA. NR 7 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 1064-1858 J9 J MAGN RESON SER A JI J. Magn. Reson. Ser. A PD OCT 15 PY 1993 VL 105 IS 1 BP 59 EP 64 DI 10.1006/jmra.1993.1248 PG 6 WC Physics, Atomic, Molecular & Chemical SC Physics GA MF841 UT WOS:A1993MF84100009 ER PT J AU BZDEGA, T CHIN, HM KIM, H JUNG, HH KOZAK, CA KLEE, WA AF BZDEGA, T CHIN, HM KIM, H JUNG, HH KOZAK, CA KLEE, WA TI REGIONAL EXPRESSION AND CHROMOSOMAL LOCALIZATION OF THE DELTA-OPIATE RECEPTOR GENE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NG108-15; IN-SITU HYBRIDIZATION; MOUSE CHROMOSOME-4; PINEAL; ANTERIOR PITUITARY ID OPIOID-PEPTIDES; RAT; MORPHINE; CLONING; BINDING; FOREBRAIN; SITES; CDNA AB The delta opiate receptor gene has been cloned from the mouse neuroblastoma-rat glioma hybrid cell NG108-15. The clone that we isolated is apparently identical to that reported by Evans et al. [Evans, C. J., Keith, D. E., Jr., Morrison, H., Magendzo, K. & Edwards, R. H. (1992) Science 258, 1952-1955] and essentially identical with that of Kieffer et al. [Kieffer, B. L., Befort, K., Gaveriaux-Ruff, C. & Hirth, C. G. (1992) Proc. Natl. Acad. Sci. USA 89, 12048-12052]. We have found full-length transcripts of the gene in mouse brain but in no other tissues examined. Within the brain the gene is expressed at low levels in many regions but transcripts are found in particularly large amounts in the anterior pituitary and pineal glands. Since these tissues are located outside the blood-brain barrier, opioid peptides easily can reach receptors in these areas from the blood. The gene, which is present as a single copy, has been mapped to the distal region of mouse Chromosome 4. C1 NINCDS,NEUROCHEM LAB,BETHESDA,MD 20892. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. RP BZDEGA, T (reprint author), NIMH,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 33 TC 57 Z9 61 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 15 PY 1993 VL 90 IS 20 BP 9305 EP 9309 DI 10.1073/pnas.90.20.9305 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MC570 UT WOS:A1993MC57000016 PM 8415697 ER PT J AU SATO, TN QIN, Y KOZAK, CA AUDUS, KL AF SATO, TN QIN, Y KOZAK, CA AUDUS, KL TI TIE-1 AND TIE-2 DEFINE ANOTHER CLASS OF PUTATIVE RECEPTOR TYROSINE KINASE GENES EXPRESSED IN EARLY EMBRYONIC VASCULAR SYSTEM SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BLOOD-BRAIN-BARRIER; SIGNAL TRANSDUCTION; GROWTH-FACTOR; DROSOPHILA-MELANOGASTER; TRANSMEMBRANE PROTEIN; ENDOTHELIAL-CELLS; MODEL SYSTEM; MOUSE; SEQUENCES; CHROMOSOME-14 AB We report the molecular cloning and characterization of two structurally related putative receptor tyrosine kinases, encoded by distinct genes (tie-1 and tie-2) on mouse chromosome 4. Both tie-1 and tie-2 encode receptor proteins possessing unique multiple extracellular domains: two immunoglobulin-like loop domains flanking three epidermal growth factor repeats followed by three fibronectin-type III repeats. Both genes are expressed in early embryonic vascular system and in maternal decidual vascular endothelial cells, where the vasculature undergoes an active angiogenesis. tie-2, but not tie-1, expression was also detected in extraembryonic mesoderm of the amnion. tie-1, but not tie-2, is expressed in an acute myelogenic cell line in vitro. tie-1 and tie-2 may form another class within the receptor tyrosine kinase gene family, and further characterization of these genes and identification of their putative ligands should define the nature of the signal-transduction cascades underlying early vascular system development, as well as their differential roles in mesodermal, cells of the amniotic and myeloid lineages. C1 UNIV KANSAS,DEPT PHARMACEUT CHEM,LAWRENCE,KS 66047. NIAID,MOLEC MICROBIOL LAB,VIRAL BIOL SECT,BETHESDA,MD 20892. RP SATO, TN (reprint author), ROCHE INST MOLEC BIOL,ROCHE RES CTR,NUTLEY,NJ 07110, USA. NR 31 TC 347 Z9 360 U1 1 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 15 PY 1993 VL 90 IS 20 BP 9355 EP 9358 DI 10.1073/pnas.90.20.9355 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MC570 UT WOS:A1993MC57000026 PM 8415706 ER PT J AU MAJOR, F GAUTHERET, D CEDERGREN, R AF MAJOR, F GAUTHERET, D CEDERGREN, R TI REPRODUCING THE 3-DIMENSIONAL STRUCTURE OF A TRANSFER-RNA MOLECULE FROM STRUCTURAL CONSTRAINTS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PHENYLALANINE TRANSFER-RNA AB The three-dimensional structure of yeast tRNA(Phe) was reproduced at atomic resolution with the automated RNA modeling program MC-SYM, which is based on a constraint-satisfaction algorithm. Structural constraints used in the modeling were derived from the secondary structure, four tertiary base pairs, and other information available prior to the determination of the x-ray crystal structure of the tRNA. The program generated 26 solutions (models), all of which had the familiar ''L'' form of tRNA and root-mean-square deviations from the crystal structure in the range of 3.1-3.8 angstrom. The interaction between uridine-8 and adenosine-14 was crucial in the modelling procedure, since only this among the tertiary pairs is necessary and sufficient to reproduce the L form of tRNA. Other tertiary interactions were critical in reducing the number of solutions proposed by the program. C1 UNIV MONTREAL,DEPT BIOCHIM,MONTREAL H3C 3J7,QUEBEC,CANADA. RP MAJOR, F (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894, USA. NR 14 TC 49 Z9 50 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 15 PY 1993 VL 90 IS 20 BP 9408 EP 9412 DI 10.1073/pnas.90.20.9408 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MC570 UT WOS:A1993MC57000037 PM 8415714 ER PT J AU MOCK, BA KRALL, MM DOSIK, JK AF MOCK, BA KRALL, MM DOSIK, JK TI GENETIC-MAPPING OF TUMOR SUSCEPTIBILITY GENES INVOLVED IN MOUSE PLASMACYTOMAGENESIS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MOLECULAR-CLONING; MULTIPLE-MYELOMA; CYTOGENETIC ANALYSIS; BALB/C MICE; CELLS; EXPRESSION; CHROMOSOME; LOCUS; TYPE-1; CHAIN AB Plasmacytomas (PCTs) were induced in 47% of BALB/cAnPt mice by the intraperitoneal injection of pristane, in 2% of (BALB/c x DBA/2N)F1, and in 11% of 773 BALB/cAnPt x (BALB/cAnPt x DBA/2N)F1 N2 backcross mice. This result indicates a multigenic mode of inheritance for PCT susceptibility. To locate genes controlling this complex genetic trait, tumor susceptibility in backcross progeny generated from BALB/c and DBA/2N (resistant) mice was correlated with alleles of 83 marker loci. The genotypes of the PCT-susceptible progeny displayed an excess homozygosity for BALB/c alleles within a 32-centimorgan stretch of mouse chromosome 4 (>95% probability of linkage) with minimal recombination (12%) near Gt10. Another susceptibility gene on mouse chromosome 1 may be linked to Fcgr2 (90% probability of linkage); there were excess heterozygotes for Fcgr2 among the susceptible progeny and excess homozygotes among the resistant progeny. Regions of mouse chromosomes 4 and 1 that are correlated with PCT susceptibility share extensive linkage homology with regions of human chromosome 1 that have been associated with cytogenetic abnormalities in multiple myeloma and lymphoid, breast, and endocrine tumors. RP MOCK, BA (reprint author), NCI,GENET LAB,BLDG 37,ROOM 2B-08,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CB-21075] NR 68 TC 89 Z9 89 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 15 PY 1993 VL 90 IS 20 BP 9499 EP 9503 DI 10.1073/pnas.90.20.9499 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MC570 UT WOS:A1993MC57000056 PM 8105477 ER PT J AU SCHAAD, O ZHOU, HX SZABO, A EATON, WA HENRY, ER AF SCHAAD, O ZHOU, HX SZABO, A EATON, WA HENRY, ER TI SIMULATION OF THE KINETICS OF LIGAND-BINDING TO A PROTEIN BY MOLECULAR-DYNAMICS - GEMINATE REBINDING OF NITRIC-OXIDE TO MYOGLOBIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PICOSECOND KINETICS; CHEMICAL DYNAMICS; LASERS ID CARBON-MONOXIDE; HEME-PROTEINS; RELAXATION DYNAMICS; HEMOGLOBIN; PHOTODISSOCIATION; CARBONMONOXYHEMOGLOBIN; RECOMBINATION; PHOTOLYSIS; RESOLUTION; PROTOHEME AB We have begun to use molecular dynamics to simulate the kinetics of nitric oxide rebinding to myoglobin after photodissociation. Rebinding was simulated using a potential function that switches smoothly between a nonbinding potential and a binding potential as a function of the position and orientation of the ligand, with no barrier arising from the crossing of potential surfaces of different electron spin. In 96 of 100 trajectories, the ligand rebound in <15 ps. The kinetic progress curve was obtained by determining the time in each trajectory at which the ligand rebound and then calculating the fraction of unbound ligands as a function of time. The curve can be well reproduced by a simple model based on the dynamics of a Langevin particle moving on a one-dimensional potential of mean force calculated from nonreactive protein trajectories. The rate of escape from the energy well adjacent to the heme is in good agreement with the value calculated from experimental data, suggesting that a multiple-well model provides a plausible explanation for the nonexponential rebinding kinetics. A transition-state analysis suggests that protein conformational relaxation coupled to the displacement of the iron from the heme plane is an unlikely cause for the nonexponential rebinding of nitric oxide. RP SCHAAD, O (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. RI Szabo, Attila/H-3867-2012; Henry, Eric/J-3414-2013 OI Henry, Eric/0000-0002-5648-8696 NR 31 TC 44 Z9 45 U1 1 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 15 PY 1993 VL 90 IS 20 BP 9547 EP 9551 DI 10.1073/pnas.90.20.9547 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MC570 UT WOS:A1993MC57000066 PM 8415739 ER PT J AU DOHLMAN, HG GOLDSMITH, P SPIEGEL, AM THORNER, J AF DOHLMAN, HG GOLDSMITH, P SPIEGEL, AM THORNER, J TI PHEROMONE ACTION REGULATES G-PROTEIN ALPHA-SUBUNIT MYRISTOYLATION IN THE YEAST SACCHAROMYCES-CEREVISIAE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE POSTTRANSLATIONAL MODIFICATION; MUTANTS; ADAPTATION ID NUCLEOTIDE-BINDING PROTEIN; KINASE-C SUBSTRATE; MEMBRANE ASSOCIATION; SIGNAL TRANSDUCTION; N-MYRISTOYLATION; MYRISTIC ACID; GENE-PRODUCT; RESPONSE PATHWAY; FACTOR RECEPTOR; GAMMA-SUBUNITS AB Myristic acid (C14:0) is added to the N-terminal glycine residue of the alpha subunits of certain receptor-coupled guanine nucleotide-binding regulatory proteins (G proteins). The Galpha subunit (GPA1 gene product) coupled to yeast pheromone receptors exists as a pool of both myristoylated and unmyristoylated species. After treatment of MATa cells with alpha factor, the myristoylated form of Gpa1p increases dramatically, and the unmyristoylated form decreases concomitantly. This pheromone-stimulated shift depends on the function of STE2 (alpha-factor receptor), STE11 (a protein kinase in the response pathway), and NMT1 (myristoyl-CoA:protein N-myristoyltransferase) genes and uses the existing pool of fatty acids (is not blocked by cerulenin). Myristoylated Gpa1p persists long after pheromone is removed. Because myristoylation is essential for proper Galpha-Gbetagamma association and receptor coupling, pheromone-dependent stimulation of Gpa1p myristoylation may be an important contributing factor in adaptation after signal transmission. C1 UNIV CALIF BERKELEY,DEPT MOLEC & CELL BIOL,DIV BIOCHEM & MOLEC BIOL,ROOM 401,BERKELEY,CA 94720. NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM21841] NR 65 TC 52 Z9 53 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 15 PY 1993 VL 90 IS 20 BP 9688 EP 9692 DI 10.1073/pnas.90.20.9688 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MC570 UT WOS:A1993MC57000095 PM 8415763 ER PT J AU BRUHN, KW NELMS, K BOULAY, JL PAUL, WE LENARDO, MJ AF BRUHN, KW NELMS, K BOULAY, JL PAUL, WE LENARDO, MJ TI MOLECULAR DISSECTION OF THE MOUSE INTERLEUKIN-4 PROMOTER SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE LYMPHOKINE; TRANSCRIPTION FACTORS; GENE; T-LYMPHOCYTES ID T-CELL RECEPTOR; FUNCTIONAL-ANALYSIS; DOWN-REGULATION; GENE; IL-4; LINES; DISTINCT; ENHANCER; SUBSETS; ANTIGEN AB Understanding the molecular mechanisms regulating the expression of interleukin 4 (IL-4) may shed light on the differentiation of lymphokine-producing phenotypes of CD4+ T cells. We have identified two DNA segments that are necessary for full phorbol 12-myristate 13-acetate (PMA)-induced activity of the IL-4 promoter region in the thymoma cell line EL4. Through deletion and mutation analyses, one of these segments (-57 through -47) was shown to be indispensable for promoter function. We designated this sequence consensus sequence 1 (CS1), as it shares homology with a sequence (ATTTTCCNNTG) that appears five times in the proximal 302-base-pair (bp) region 5' of the gene. We examined CS1 in further detail, as well as a second consensus sequence, CS2, located at nucleotides -75 through -65; both are within a minimal 83-bp construct that expresses full promoter activity. CS1- and CS2-spanning oligonucleotides bound apparently distinct PMA-inducible, sequence-specific factors in mobility-shift assays. Multimer constructs linking CS1- or CS2-spanning oligonucleotides to a heterologous promoter revealed that the CS1 construct had the greater enhancer activity in EL4 cells. Mutating the CS1 sequence within the context of the 302-bp promoter abolished all activity of the promoter, while mutating the CS2 sequence alone had little effect. Furthermore, a CS1 multimer could drive a heterologous promoter in an IL-4-producing [helper T-cell type 2 (T(H)2-type)] T-cell clone but not in a non-IL-4-producing (T(H)1-type) clone, suggesting a mechanism by which IL-4 production could be differentially regulated in T(H) subsets. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RI Bruhn, Kevin/F-9772-2013 NR 36 TC 58 Z9 58 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 15 PY 1993 VL 90 IS 20 BP 9707 EP 9711 DI 10.1073/pnas.90.20.9707 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MC570 UT WOS:A1993MC57000099 PM 8415766 ER PT J AU RICE, WG SCHAEFFER, CA GRAHAM, L BU, M MCDOUGAL, JS ORLOFF, SL VILLINGER, F YOUNG, M OROSZLAN, S FESEN, MR POMMIER, Y MENDELEYEV, J KUN, E AF RICE, WG SCHAEFFER, CA GRAHAM, L BU, M MCDOUGAL, JS ORLOFF, SL VILLINGER, F YOUNG, M OROSZLAN, S FESEN, MR POMMIER, Y MENDELEYEV, J KUN, E TI THE SITE OF ANTIVIRAL ACTION OF 3-NITROSOBENZAMIDE ON THE INFECTIVITY PROCESS OF HUMAN-IMMUNODEFICIENCY-VIRUS IN HUMAN-LYMPHOCYTES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ZINC FINGER; PROVIRAL DNA BLOCK ID MURINE LEUKEMIA-VIRUS; NUCLEOCAPSID PROTEIN; HIV-1 PROTEASE; ZINC-FINGERS; POLY(ADP-RIBOSE) POLYMERASE; BINDING DOMAINS; TOPOISOMERASE-I; DNA-BINDING; RETROVIRUSES; RNA AB The C-nitroso compound 3-nitrosobenzamide, which has been shown to remove zinc from the retroviral-type zinc finger of p7NC nucleocapsid proteins, inhibits acute infection of human immunodeficiency virus type 1 in cultured human lymphocytes. The attachment of the virus to lymphocytes and the activities of critical viral enzymes, such as reverse transcriptase, protease, and integrase, are not affected by 3-nitrosobenzamide. However, the process of reverse transcription to form proviral DNA is effectively abolished by the drug, identifying the mode of action of 3-nitrosobenzamide as interrupting the role of p7NC in accurate proviral DNA synthesis during the infectious phase of the virus life cycle. C1 SAN FRANCISCO STATE UNIV,ROMBERG TIBURON CTR,ENVIRONM TOXICOL & CHEM LAB,TIBURON,CA 94920. CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,DIV HIV AIDS,IMMUNOL BRANCH,ATLANTA,GA 30333. EMORY UNIV,SCH MED,DEPT PATHOL & LAB MED,ATLANTA,GA 30322. NCI,FREDERICK CANC RES & DEV CTR,BASIC RES PROGRAM,ADV BIOSCI LABS,FREDERICK,MD 21702. NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. SAN FRANCISCO STATE UNIV,OCTAMER RES FDN,TIBURON,CA 94920. RP RICE, WG (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,ANTIVIRAL DRUG MECHANISMS LAB,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102, N01-CO-74101] NR 38 TC 72 Z9 72 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 15 PY 1993 VL 90 IS 20 BP 9721 EP 9724 DI 10.1073/pnas.90.20.9721 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MC570 UT WOS:A1993MC57000102 PM 7692451 ER PT J AU THOMAS, A AF THOMAS, A TI NIDR REPORT SO SCIENCE LA English DT Letter RP THOMAS, A (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 15 PY 1993 VL 262 IS 5132 BP 321 EP 321 DI 10.1126/science.262.5132.321 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MB859 UT WOS:A1993MB85900006 PM 17789905 ER PT J AU SHENKER, A LAUE, L KOSUGI, S MERENDINO, JJ MINEGISHI, T CUTLER, GB AF SHENKER, A LAUE, L KOSUGI, S MERENDINO, JJ MINEGISHI, T CUTLER, GB TI A CONSTITUTIVELY ACTIVATING MUTATION OF THE LUTEINIZING-HORMONE RECEPTOR IN FAMILIAL MALE PRECOCIOUS PUBERTY SO NATURE LA English DT Article ID ALPHA-1B-ADRENERGIC RECEPTOR; CHORIONIC-GONADOTROPIN; SEXUAL PRECOCITY; GENE; SUBSTITUTIONS; RHODOPSIN; RAT; LH AB FAMILIAL male precocious puberty (FMP) is a gonadotropin-independent disorder that is inherited in an autosomal dominant, male-limited pattern1-5. Affected males generally exhibit signs of puberty by age 4. Testosterone production and Leydig cell hyperplasia occur in the context of prepubertal levels of luteinizing hormone (LH)3-5. The LH receptor is a member of the family of G-protein-coupled receptors6,7, and we hypothesized that FMPP might be due to a mutant receptor that is activated in the presence of little or no agonist8-12 . A single A --> G base change that results in substitution of glycine for aspartate at position 578 in the sixth transmembrane helix of the LH receptor was found in affected individuals from eight different families. Linkage of the mutation to FMPP was supported by restriction-digest analysis. COS-7 cells expressing the mutant LH receptor exhibited markedly increased cyclic AMP production in the absence of agonist, suggesting that autonomous Leydig cell activity in FMPP is caused by a constitutively activated LH receptor. C1 NIDDK,BIOCHEM & METAB LAB,CELL REGULAT SECT,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. KYOTO UNIV,SCH MED,DEPT LAB MED,KYOTO 606,JAPAN. GUNMA UNIV,SCH MED,DEPT OBSTET & GYNECOL,MAEBASHI,GUNMA 371,JAPAN. RP SHENKER, A (reprint author), NIDDK,MOLEC PATHOPHYSIOL BRANCH,BLDG 10,ROOM 8C-101,BETHESDA,MD 20892, USA. NR 30 TC 546 Z9 558 U1 1 U2 5 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 14 PY 1993 VL 365 IS 6447 BP 652 EP 654 DI 10.1038/365652a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MB846 UT WOS:A1993MB84600060 PM 7692306 ER PT J AU CLARK, M WEISS, SRB POST, RM AF CLARK, M WEISS, SRB POST, RM TI AUTORADIOGRAPHIC ANALYSIS OF SEROTONIN RECEPTORS AND TRANSPORTER IN KINDLED RAT-BRAIN SO NEUROSCIENCE LETTERS LA English DT Article DE HIPPOCAMPUS; SEROTONIN RECEPTOR; SEROTONIN TRANSPORTER; ADENOSINE A1 RECEPTOR; AUTORADIOGRAPHY; KINDLING; RAT BRAIN ID MESSENGER-RNA; 5-HT1A RECEPTOR; HIPPOCAMPUS; SEIZURES; AMYGDALA; EXPRESSION; FLUOXETINE; BINDING; INVIVO AB While serotonin (5-HT) has been shown to be anticonvulsant in several types of experimentally induced seizures, 5-HT receptor binding has not been investigated in the kindling model of epilepsy. The present study examined the effects of amygdala kindling on two 5-HT receptor subtypes and on the 5-HT transporter in rat brain. Kindling induced a persistent bilateral increase in 5-HT1A binding in the dentate gyrus, while 5-HT1B receptors increased only in a delayed fashion. Binding to the 5-HT transporter was transiently decreased in dentate gyrus. In cerebral cortex, binding of the three ligands was unchanged. Alterations in 5-HT receptors and the 5-HT transporter may endogenously modulate kindled seizures. Additionally, autoradiography of adenosine A1 receptors revealed no change for these receptors in any brain region. RP CLARK, M (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,BETHESDA,MD 20892, USA. NR 25 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD OCT 14 PY 1993 VL 161 IS 1 BP 21 EP 26 DI 10.1016/0304-3940(93)90130-D PG 6 WC Neurosciences SC Neurosciences & Neurology GA MA888 UT WOS:A1993MA88800006 PM 8255539 ER PT J AU MILLS, JL AF MILLS, JL TI DATA TORTURING SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material RP MILLS, JL (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 5 TC 116 Z9 117 U1 1 U2 4 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 14 PY 1993 VL 329 IS 16 BP 1196 EP 1199 DI 10.1056/NEJM199310143291613 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA MA667 UT WOS:A1993MA66700013 PM 8166792 ER PT J AU BITTNER V WEINER, DH YUSUF, S ROGERS, WJ MCINTYRE, KM BANGDIWALA, SI KRONENBERG, MW KOSTIS, JB KOHN, RM GUILLOTTE, M GREENBERG, B WOODS, PA BOURASSA, MG AF BITTNER, V WEINER, DH YUSUF, S ROGERS, WJ MCINTYRE, KM BANGDIWALA, SI KRONENBERG, MW KOSTIS, JB KOHN, RM GUILLOTTE, M GREENBERG, B WOODS, PA BOURASSA, MG TI PREDICTION OF MORTALITY AND MORBIDITY WITH A 6-MINUTE WALK TEST IN PATIENTS WITH LEFT-VENTRICULAR DYSFUNCTION SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CONGESTIVE-HEART-FAILURE; EXERCISE CAPACITY; ISOSORBIDE DINITRATE; FUNCTIONAL-CAPACITY; PROGNOSTIC VALUE; PERFORMANCE; DISEASE; DETERMINANTS; HYDRALAZINE; VARIABLES AB Objective.-To study the potential usefulness of the 6-minute walk test, a self-paced submaximal exercise test, as a prognostic indicator in patients with left ventricular dysfunction. Design.-Data were collected during a prospective cohort study, the Studies of Left Ventricular Dysfunction (SOLVD) Registry Substudy. Setting.-Twenty tertiary care hospitals in the United States, Canada, and Belgium. Participants.-A stratified random sample of 898 patients from the SOLVD Registry who had either radiological evidence of congestive heart failure and/or an ejection fraction of 0.45 or less were enrolled in the substudy and underwent a detailed clinical evaluation including a 6-minute walk test. Patients were followed up for a mean of 242 days. Outcome Measures.-Mortality and hospitalization. Results.-During follow-up, 52 walk-test participants (6.2%) died and 252 (30.3%) were hospitalized. Hospitalization for congestive heart failure occurred in 78 participants (9.4%), and the combined endpoint of death or hospitalization for congestive heart failure occurred in 114 walk-test participants (13.7%). Compared with the highest performance level, patients in the lowest performance level had a significantly greater chance of dying (10.23% vs 2.99%; P=.01), of being hospitalized (40.91% vs 19.90%; P=.002), and of being hospitalized for heart failure (22.16% vs 1.990/o; P<.0001). In a logistic regression model, ejection fraction and distance walked were equally strong and independent predictors of mortality and heart failure hospitalization rates during follow-up. Conclusion.-The 6-minute walk test is a safe and simple clinical tool that strongly and independently predicts morbidity and mortality in patients with left ventricular dysfunction. C1 OREGON HLTH SCI UNIV, DEPT MED, PORTLAND, OR 97201 USA. UNIV N CAROLINA, DEPT BIOSTAT, COLLABORAT STUDIES COORDINATING CTR, CHAPEL HILL, NC 27514 USA. VET AFFAIRS MED CTR, BOSTON, MA USA. UNIV MED & DENT NEW JERSEY, DEPT MED & PHARMACOL, NEW BRUNSWICK, NJ USA. SUNY Buffalo, DEPT MED, BUFFALO, NY 14260 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. VANDERBILT UNIV, MED CTR, SCH MED, DEPT MED, NASHVILLE, TN 37232 USA. MONTREAL HEART INST, RES CTR, MONTREAL H1T 1C8, QUEBEC, CANADA. SUNY Buffalo, DEPT RES, BUFFALO, NY 14260 USA. VET AFFAIRS MED CTR, MANCHESTER, NH USA. NIH, DIV EPIDEMIOL & CLIN APPLICAT, BETHESDA, MD 20892 USA. BRIGHAM & WOMENS HOSP, DEPT MED, BOSTON, MA 02115 USA. BRIGHAM & WOMENS HOSP, DEPT RES, BOSTON, MA 02115 USA. RP BITTNER V (reprint author), UNIV ALABAMA, DEPT MED, DIV CARDIOVASC DIS, THT 328 UAB STN, BIRMINGHAM, AL 35294 USA. OI Bourassa, Martial G./0000-0002-4439-8650 FU NHLBI NIH HHS [N01 HC55001] NR 28 TC 476 Z9 521 U1 0 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 13 PY 1993 VL 270 IS 14 BP 1702 EP 1707 DI 10.1001/jama.270.14.1702 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA MA294 UT WOS:A1993MA29400026 PM 8411500 ER PT J AU BRECHNER, RJ COWIE, CC HOWIE, LJ HERMAN, WH WILL, JC HARRIS, MI AF BRECHNER, RJ COWIE, CC HOWIE, LJ HERMAN, WH WILL, JC HARRIS, MI TI OPHTHALMIC EXAMINATION AMONG ADULTS WITH DIAGNOSED DIABETES-MELLITUS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RETINOPATHY; PREVALENCE; RISK; CARE; AGE; YR AB Objective.-To assess whether adults with diagnosed diabetes in the United States are receiving recommended eye examinations for detection of diabetic retinopathy and what factors are associated with receiving them. Design, Setting, and Participants.-The design was a cross-sectional survey of the civilian, noninstitutionalized US population 18 years of age or older, based on the 1989 National Health Interview Survey. A multistage probability sampling strategy was used to identify a representative sample of 84 572 persons. A questionnaire on diabetes was administered to all subjects with diagnosed diabetes (n=2405). Main Outcome Measure.-A dilated eye examination in the past year. Main Results.-Of all adults with diagnosed diabetes in the United States, only 49% had a dilated eye examination in the past year. This included 57% of people with insulin-dependent diabetes mellitus (IDDM), 55% with insulin-treated noninsulin-dependent diabetes mellitus (NIDDM), and 44% with NIDDM not treated with insulin. Even among diabetics at high risk of vision loss because of retinopathy or long duration of diabetes, the proportion with a dilated eye examination was only 61% and 57%, respectively. By logistic regression, the probability of a dilated eye examination among persons with NIDDM increased with older age, higher socioeconomic status, and having attended a diabetes education class. The probability of a dilated eye examination was not independently related to race, duration of diabetes, frequency of physician visits for diabetes, or health insurance. Conclusions.-About half of adults with diabetes in the United States are not receiving timely and recommended eye care to detect and treat retinopathy. Wide-spread interventions, including patient and professional education, are needed to ensure that diabetic patients who are not receiving appropriate eye care have an annual dilated eye examination to detect retinopathy and prevent vision loss. C1 NIDDKD, NATL DIABET DATA GRP, WESTWOOD BLDG, ROOM 620, BETHESDA, MD 20892 USA. CTR DIS CONTROL & PREVENT, NATL CTR CHRON DIS PREVENT & HLTH PROMOT, DIV DIABET TRANSLAT, ATLANTA, GA USA. SCI SYST INC, BETHESDA, MD USA. NATL CTR HLTH STAT, DIV HLTH INTERVIEW STAT, HYATTSVILLE, MD 20782 USA. NR 38 TC 179 Z9 183 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 13 PY 1993 VL 270 IS 14 BP 1714 EP 1718 DI 10.1001/jama.270.14.1714 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA MA294 UT WOS:A1993MA29400028 PM 8411502 ER PT J AU CHEN, F RITTER, JK WANG, MG MCBRIDE, OW LUBET, RA OWENS, IS AF CHEN, F RITTER, JK WANG, MG MCBRIDE, OW LUBET, RA OWENS, IS TI CHARACTERIZATION OF A CLONED HUMAN DIHYDROTESTOSTERONE ANDROSTANEDIOL UDP-GLUCURONOSYLTRANSFERASE AND ITS COMPARISON TO OTHER STEROID ISOFORMS SO BIOCHEMISTRY LA English DT Article ID INSITU HYBRIDIZATION; ANDROGEN METABOLISM; COS-1 CELLS; RAT-LIVER; ACID; LOCALIZATION; EXPRESSION; CDNAS; GENE; GLUCURONIDE AB A human cDNA, UDPGTh-3, encoding a dihydrotestosterone/5alpha-androstane-3alpha,17beta-diol UDP-glucuronosyltransferase (transferase) has been isolated and characterized. The nucleotide sequence of UDPGTh-3 encodes a 530 amino acid protein with a typical membrane insertion-signal peptide, a membrane-anchoring domain, and three potential asparagine-linked glycosylation sites. Alignment shows that this encoded isozyme is 96% identical to an apparent estriol-metabolizing isoform, HLUG4 [Coffman, B. L., et al., (1990) Arch. Biochem. Biophys. 281, 170-175]. The udpgth-3 isozyme is 78% identical to two other steroid isoforms, HLUG25 (udpgth-1) [Jackson, M. R., et al. (1987) Biochem. J. 242, 581-588; Ritter, J. K., et al. (1992) Biochemistry 31, 3409-3414] and udpgth-2 [Ritter, J. K., et al. (1990) J. Biol. Chem. 265, 7900-7906]. udpgth-2 and udpgth-1 metabolized parallel substrates (stereospecific estriols, 3,4-catechol estrogens, and the bile salt hyodeoxycholate), except that udpgth-2 was 100-fold more effective than udpgth-1. The mRNA encoding udpgth-3 is 2.4 kb in size and is present in liver, prostate, and testis; the mRNA encoding udpgth-2 is located in liver and kidney, whereas that for udpgth-1 is liver-specific. Each of the liver mRNA species encoding udpgth-3, udpgth-2, or udpgth-1 was induced 2.5-3-fold by phenobarbital treatment of the Erythrocebus patas monkey. In 16 human liver mRNA samples, the message encoding udpgth-3 was generally uniformly expressed and that for udpgth-1 exhibited wide variations in its level, whereas that for udpgth-2 was barely detectable in nine samples and not detectable in the others. Three samples contained no message for either isoform. Substrate turnover by udpgth-3 is ranked as follows: phenolphthalein > 5alpha-androstane-3alpha,17,beta-diol > 5alpha-dihydrotestosterone = 4-hydroxybiphenyl > phenolsulfonphthalein (phenol red) > phenolphthalin. Genes encoding udpgth-3, udpgth-2, and udpgth-1 mapped to human chromosome 4 with genomic DNA from human/mouse and human/hamster somatic cell hybrids; the genes encoding udpgth-1 and udpgth-2 mapped specifically to band 4q28. udpgth-3 exhibited similar K(m) values both for 5alpha-dihydrotestosterone (10 muM) and for its metabolite, 5alpha-androstane-3alpha-17beta-diol (12.5 muM). Although the role of glucuronidation in the regulation of 5alpha-dihydrotestosterone levels is not known, the location of the message for this isoform in target tissues, testis and prostate, indicates that the isoform is, most likely, important in the control of hormonal levels and, thus, in 5alpha-dihydrotestosterone action. Furthermore, a critical role for udpgth-3 is suggested in light of the absence of its messenger RNA but the presence of that for four other transferase isoforms examined in the liver of a patient with benign prostate hyperplasia, a condition associated with depressed glucuronidation of dihydrotestosterone. C1 NICHHD,HUMAN GENET BRANCH,GENET DISORDERS DRUG METAB SECT,BLDG 10,ROOM 95-242,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NCI,COMPARAT CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 37 TC 105 Z9 106 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 12 PY 1993 VL 32 IS 40 BP 10648 EP 10657 DI 10.1021/bi00091a015 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MB497 UT WOS:A1993MB49700015 PM 8399210 ER PT J AU VAZIRI, SM EVANS, JC LARSON, MG WILSON, PWF AF VAZIRI, SM EVANS, JC LARSON, MG WILSON, PWF TI THE IMPACT OF FEMALE HORMONE USAGE ON THE LIPID PROFILE - THE FRAMINGHAM OFFSPRING STUDY SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; POSTMENOPAUSAL ESTROGEN REPLACEMENT; DENSITY-LIPOPROTEIN CHOLESTEROL; ORAL-CONTRACEPTIVE USE; CARDIOVASCULAR-DISEASE; PLASMA-LIPOPROTEINS; SERUM-LIPOPROTEINS; THERAPY; WOMEN; PROGESTOGENS AB Background: Exogenous female hormone use appears to affect cardiovascular disease risk in both premenopausal and postmenopausal women. The purpose of this study was to evaluate the impact of exogenous female hormone usage on the lipid profile among premenopausal and postmenopausal women. Methods: One thousand nine hundred thirty female participants of the Framingham Offspring study comprised the study population. Of the 992 premenopausal subjects, 57 were current oral contraceptive users; among the 938 post-menopausal subjects, 80 were current hormone users. The influence of hormone use on lipid and lipoprotein levels was determined using multivariable linear regression models that adjusted for age, body mass index, smoking, alcohol intake, beta-blocker, and diuretic therapy. Adjusted least-squares means were calculated for each lipid and lipoprotein according to female hormone usage and menopausal status. Results: In the premenopausal analysis, pooled oral contraceptive use was significantly related to increased levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol and apolipoprotein A-I. Increased estrogen content was inversely associated with low-density lipoprotein cholesterol, and apolipoprotein B levels, while increased progestin content was inversely related to high-density lipoprotein cholesterol and apolipoprotein A-I levels. Among postmenopausal women, use of premarin only was significantly associated with increased high-density lipoprotein cholesterol and apolipoprotein A-I levels. Combination use of premarin and provera was significantly associated with increased apolipoprotein A-I levels; less powerful but still significant associations with increased high-density lipoprotein cholesterol and decreased low-density lipoprotein cholesterol were also observed. Conclusion: In this cross-sectional analysis, oral contraceptive use is associated with both favorable and unfavorable lipid alterations with respect to atherogenic risk. Among postmenopausal women, hormone replacement therapy (both premarin only and combined premarin and provera) appears to be associated with favorable effects on the lipid profile. C1 NHLBI,BETHESDA,MD 20892. RP VAZIRI, SM (reprint author), FRAMINGHAM HEART DIS EPIDEMIOL STUDY,5 THURBER ST,FRAMINGHAM,MA 01701, USA. NR 48 TC 45 Z9 45 U1 0 U2 1 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 11 PY 1993 VL 153 IS 19 BP 2200 EP 2206 DI 10.1001/archinte.153.19.2200 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA MA527 UT WOS:A1993MA52700003 PM 8215723 ER PT J AU HYUN, SW KIM, SJ PARK, K RHO, HM LEE, YI AF HYUN, SW KIM, SJ PARK, K RHO, HM LEE, YI TI CHARACTERIZATION OF THE P4 PROMOTER REGION OF THE HUMAN INSULIN-LIKE GROWTH FACTOR-II GENE SO FEBS LETTERS LA English DT Article DE IGF-II P4 PROMOTOR; POSITIVE REGULATORY ELEMENT; NEGATIVE REGULATORY ELEMENT; SP1 BINDING SEQUENCE; EGR-1 ELEMENT ID TRANSCRIPTION INITIATION; MESSENGER-RNAS; 2 PROMOTERS; EXPRESSION; ELEMENTS; ACTIVATION; PROTEIN; ACID AB The human insulin-like growth factor II (IGF-II) gene contains four promoters (P1, P2, P3 and P4). In order to determine the mechanism by which the P4 promoter is controlled, the human IGF-II P4 promoter was analyzed in cell lines. DNA sequence analysis of the human IGF-II P4 promoter gene showed that the P4 promoter region contains a TATA-like sequence and several G + C rich regions which are essential for transcription. Analysis of the transcription initiation site by S1 nuclease mapping revealed two transcription start sites; both are located immediately behind TATA-like sequence. To determine the location of sites that may be important for the function of the human IGF-II P4 promoter, we constructed chimeric genes of the human IGF-II P4 promoter fused to the coding region for chloramphenicol acetyltransferase (CAT). These constructs were transfected into HepG2, PLC/PRF/5, G401 and A549 cells, and were examined for CAT activity. All transfected cells showed a similar profile of CAT activity. Sequences responsible for putative enhancer and silencer regions were identified and the 5'flanking sequences of the human IGF-II P4 promoter contain negative regulatory regions (-213 to -174). The 53-base pair fragment located between 111 and 59 base pairs upstream of the start site contains positive regulatory activity. Gel mobility shift assay showed that Sp1 and another proteins might be involved in positive regulation of the human IGF-II P4 promoter. C1 KIST,GENET ENGN RES INST,MOLEC GENET LAB,DAEJON,SOUTH KOREA. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. SEOUL NATL UNIV,DEPT MOLEC BIOL,SEOUL 151,SOUTH KOREA. NR 26 TC 11 Z9 14 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 11 PY 1993 VL 332 IS 1-2 BP 153 EP 158 DI 10.1016/0014-5793(93)80503-M PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA MA778 UT WOS:A1993MA77800034 PM 8405433 ER PT J AU GU, LY HUANG, SM SANDER, M AF GU, LY HUANG, SM SANDER, M TI DROSOPHILA RRP1 COMPLEMENTS ESCHERICHIA-COLI XTH NFO MUTANTS - PROTECTION AGAINST BOTH OXIDATIVE AND ALKYLATION-INDUCED DNA-DAMAGE SO NUCLEIC ACIDS RESEARCH LA English DT Article ID APURINIC APYRIMIDINIC ENDONUCLEASE; ESCHERICHIA-COLI; EXONUCLEASE-III; REPAIR ENZYMES; HYDROGEN-PEROXIDE; APEX NUCLEASE; GENE; CDNA; IV; HOMOLOGY AB Drosophila Rrp1 protein has four tightly associated enzymatic activities: DNA strand transfer, ssDNA renaturation. dsDNA 3'-exonuclease and apurinic/apyrimidinic (AP) endonuclease. The carboxy-terminal region of Rrp1 is homologous to Escherichia coli exonuclease III and several eukaryotic AP endonucleases. All members of this protein family cleave abasic sites. Rrp1 protein was expressed under the control of the E.coli RNA polymerase tac promoter (pRrp1-tac) in two repair deficient E.coli strains (BW528 and LG101) lacking both exonuclease III (xth) and endonuclease IV (nfo). Rrp1 confers resistance to killing by oxidative, antitumor and alkylating agents that damage DNA (hydrogen peroxide, t-butylhydroperoxide, bleomycin, methyl methanesulfonate, and mitomycin C). Complementation of the repair deficiency by Rrp1 provides up to a two log increase in survival and requires the C-terminal nuclease region of Rrp1, but not its N-terminal region. The AP endonuclease activity in extracts from the repair deficient strain LG101 is increased up to 12-fold when the strain contains pRrp1-tac. These results indicate that pRrp1-tac directs the synthesis of active enzyme, and that the nuclease activities of Rrp1 are likely to be the cause of the increased resistance to DNA damage of the mutant cells. C1 NIEHS,GENET LAB D3-04,POB 12233,RES TRIANGLE PK,NC 27709. NR 35 TC 21 Z9 21 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT 11 PY 1993 VL 21 IS 20 BP 4788 EP 4795 DI 10.1093/nar/21.20.4788 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MD034 UT WOS:A1993MD03400021 PM 7694234 ER PT J AU KOONIN, EV AF KOONIN, EV TI A HIGHLY CONSERVED SEQUENCE MOTIF DEFINING THE FAMILY OF MUTT-RELATED PROTEINS FROM EUBACTERIA, EUKARYOTES AND VIRUSES SO NUCLEIC ACIDS RESEARCH LA English DT Note RP KOONIN, EV (reprint author), NIH,NATL LIBRARY MED,NAT CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894, USA. NR 10 TC 89 Z9 91 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT 11 PY 1993 VL 21 IS 20 BP 4847 EP 4847 DI 10.1093/nar/21.20.4847 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MD034 UT WOS:A1993MD03400033 PM 8233837 ER PT J AU BAI, G KUSIAK, JW AF BAI, G KUSIAK, JW TI CLONING AND ANALYSIS OF THE 5' FLANKING SEQUENCE OF THE RAT N-METHYL-D-ASPARTATE RECEPTOR-1 (NMDAR1) GENE SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Note DE N-METHYL-D-ASPARTATE RECEPTER-1 GENE; TRANSCRIPTION START SITE; PROMOTER; HOUSEKEEPING GENE ID TRANSCRIPTION FACTORS; MESSENGER-RNA; DNA-BINDING; ACTIVATION; CHANNEL; MEMBER; FAMILY AB We cloned and analyzed a 3.8 kb EcoRI fragment of the rat NMDAR1 gene. It contains 3 kb of promoter/enhancer region, exon 1 and a portion of intron 1. Two major transcription start sites were identified at - 276 and - 238 from the first nucleotide in codon 1. One GSG and two SP1 motifs, but no TATA/CAAT boxes, exist in the region proximal to the transcription start sites. Our results suggest that NMDAR1 has the characteristics of a housekeeping gene and may be regulated by immediate-early genes. RP BAI, G (reprint author), NIA,GERONTOL RES CTR,MOLEC NEUROBIOL UNIT,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 24 TC 48 Z9 49 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD OCT 10 PY 1993 VL 1152 IS 1 BP 197 EP 200 DI 10.1016/0005-2736(93)90249-Y PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MB696 UT WOS:A1993MB69600027 PM 8399301 ER PT J AU PSIACHOU, H MITTON, S ALAGHBANDZADEH, J HONE, J TAYLOR, SI SINCLAIR, L AF PSIACHOU, H MITTON, S ALAGHBANDZADEH, J HONE, J TAYLOR, SI SINCLAIR, L TI LEPRECHAUNISM AND HOMOZYGOUS NONSENSE MUTATION IN THE INSULIN-RECEPTOR GENE SO LANCET LA English DT Letter C1 CHARING CROSS & WESTMINSTER MED SCH,DEPT CHEM PATHOL,LONDON W6,ENGLAND. NIH,DIABET BRANCH,BETHESDA,MD 20892. RP PSIACHOU, H (reprint author), WESTMINSTER MED SCH & HOSP,LONDON,ENGLAND. NR 3 TC 28 Z9 29 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD OCT 9 PY 1993 VL 342 IS 8876 BP 924 EP 924 DI 10.1016/0140-6736(93)91970-W PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MA963 UT WOS:A1993MA96300032 PM 8105179 ER PT J AU XU, HY MITCHELL, CL AF XU, HY MITCHELL, CL TI CHELATION OF ZINC BY DIETHYLDITHIOCARBAMATE FACILITATES BURSTING INDUCED BY MIXED ANTIDROMIC PLUS ORTHODROMIC ACTIVATION OF MOSSY FIBERS IN HIPPOCAMPAL SLICES SO BRAIN RESEARCH LA English DT Article DE DIETHYLDITHIOCARBAMATE; ZINC; SEIZURE; EPILEPTIFORM ACTIVITY; BURSTING; HIPPOCAMPAL SLICE ID METHYL-D-ASPARTATE; EPILEPTIFORM ACTIVITY; PERFORANT PATH; SEIZURE SUSCEPTIBILITY; ENDOGENOUS ZN-2+; RAT HIPPOCAMPUS; KAINIC ACID; NEURONS; STIMULATION; RESPONSES AB The effect of chelation of zinc by diethyldithiocarbamate (DEDTC) on bursting of CA3 pyramidal cells induced by mixed antidromic plus orthodromic activation of mossy fibers (MP) in hippocampal slices was studied. Slices perfused in artificial cerebrospinal fluid (ACSF) with high (2.5 mM) Ca2+ rarely exhibited triggered bursting following a series of stimulus trains similar to those used in kindling. In contrast, slices perfused with DEDTC (0.1 mM) in ACSF and subsequently perfused with ACSF alone prior to initiating the stimulus trains exhibited robust triggered bursting following the stimulus trains. However, if slices perfused with ACSF containing DEDTC were then perfused with ACSF containing zinc chloride (0.5 muM) followed by ACSF alone, triggered bursting was not induced subsequent to delivering stimulus trains. It is concluded that release of zinc from the mossy fibers induced by tetanic stimulation serves to obtund bursting in CA3 pyramidal cells. C1 NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,POB 12233,RES TRIANGLE PK,NC 27709. NR 50 TC 26 Z9 26 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 8 PY 1993 VL 624 IS 1-2 BP 162 EP 170 DI 10.1016/0006-8993(93)90074-W PG 9 WC Neurosciences SC Neurosciences & Neurology GA MA059 UT WOS:A1993MA05900022 PM 8252388 ER PT J AU ECKERTMAKSIC, M MAKSIC, ZB HODOSCEK, M POLJANEC, K AF ECKERTMAKSIC, M MAKSIC, ZB HODOSCEK, M POLJANEC, K TI THE MILLS-NIXON EFFECT IN TRINDAN AND SOME RELATED TRIS-ANNELATED BENZENES SO JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM LA English DT Article ID PI; MOLECULES; CHEMISTRY; ABINITIO; RINGS AB Structural features of trindan and some related tris-annelated benzenes are examined by the SCF 3-21G procedure. It turns out that the central fragment exhibits characteristic albeit rather weak Mills-Nixon (MN) type of distortion in all studied systems. This finding is in agreement with some available accurate X-ray data. In trindan, however, X-ray measurements are less precise thus yielding less conclusive evidence. Nevertheless, if upper and lower levels of the experimental errors are taken into account, the MN effect just might be operative in this molecule too. Both theoretical and experimental geometries are interpreted in terms of the rehybridization concept caused by fusion and redistribution of the pi-density arising due to hyperconjugation with CH2 groups of annelated carbocycles. Both mechanisms act sinergistically in the same direction leading to MN deformations. C1 RUDJER BOSKOVIC INST, 41001 ZAGREB, CROATIA. NIH, BETHESDA, MD 20892 USA. JOZEF STEFAN INST, FAC SCI & MATH, 61111 LJUBLJANA, SLOVENIA. UNIV ZAGREB, 41000 ZAGREB, CROATIA. NR 40 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-1280 J9 J MOL STRUC-THEOCHEM JI Theochem-J. Mol. Struct. PD OCT 8 PY 1993 VL 104 IS 2 BP 187 EP 194 PG 8 WC Chemistry, Physical SC Chemistry GA MC575 UT WOS:A1993MC57500004 ER PT J AU SHEARER, GM CLERICI, M DALGLEISH, A AF SHEARER, GM CLERICI, M DALGLEISH, A TI ALLOIMMUNIZATION AS AN AIDS VACCINE SO SCIENCE LA English DT Letter ID IMMUNODEFICIENCY-VIRUS; T-CELL C1 ST GEORGE HOSP,SCH MED,DEPT CELLULAR & MED SCI,LONDON SW17 0RE,ENGLAND. RP SHEARER, GM (reprint author), NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892, USA. NR 18 TC 48 Z9 49 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 8 PY 1993 VL 262 IS 5131 BP 161 EP 162 DI 10.1126/science.8211133 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MA665 UT WOS:A1993MA66500002 PM 8211133 ER PT J AU LAWRENCE, CE ALTSCHUL, SF BOGUSKI, MS LIU, JS NEUWALD, AF WOOTTON, JC AF LAWRENCE, CE ALTSCHUL, SF BOGUSKI, MS LIU, JS NEUWALD, AF WOOTTON, JC TI DETECTING SUBTLE SEQUENCE SIGNALS - A GIBBS SAMPLING STRATEGY FOR MULTIPLE ALIGNMENT SO SCIENCE LA English DT Article ID HELIX-TURN-HELIX; AMINO-ACID-SEQUENCES; UNALIGNED DNA FRAGMENTS; PROTEIN-BINDING SITES; KLEBSIELLA-PNEUMONIAE; REGULATORY PROTEINS; MOLECULAR-STRUCTURE; SUBSTITUTION MATRICES; BIOLOGICAL SEQUENCES; NUCLEOTIDE-SEQUENCE AB A wealth of protein and DNA sequence data is being generated by genome projects and other sequencing efforts. A crucial barrier to deciphering these sequences and understanding the relations among them is the difficulty of detecting subtle local residue patterns common to multiple sequences. Such patterns frequently reflect similar molecular structures and biological properties. A mathematical definition of this ''local multiple alignment'' problem suitable for full computer automation has been used to develop a new and sensitive algorithm, based on the statistical method of iterative sampling. This algorithm finds an optimized local alignment model for N sequences in N-linear time, requiring only seconds on current workstations, and allows the simultaneous detection and optimization of multiple patterns and pattern repeats. The method is illustrated as applied to helix-turn-helix proteins, lipocalins, and prenyltransferases. C1 HARVARD UNIV, DEPT STAT, CAMBRIDGE, MA 02138 USA. NEW YORK STATE DEPT HLTH, WADSWORTH CTR LABS & RES, BIOMETR LAB, ALBANY, NY 12201 USA. RP LAWRENCE, CE (reprint author), NIH, NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20894 USA. FU NIMH NIH HHS [NIMH MH-31154] NR 116 TC 1146 Z9 1194 U1 3 U2 20 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD OCT 8 PY 1993 VL 262 IS 5131 BP 208 EP 214 DI 10.1126/science.8211139 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MA665 UT WOS:A1993MA66500025 PM 8211139 ER PT J AU SHIDA, Y DETERDING, LJ OHARA, K KONO, M TOMER, KB AF SHIDA, Y DETERDING, LJ OHARA, K KONO, M TOMER, KB TI MACROLIDE ANTIBIOTIC-STRUCTURE DETERMINATION BY FAST-ATOM-BOMBARDMENT TANDEM MASS-SPECTROMETRY SO TETRAHEDRON LA English DT Article ID ESCHERICHIA-COLI; LIQUID-CHROMATOGRAPHY; HIGHLY RESISTANT; ERYTHROMYCIN; STRAIN; BIOMOLECULES; 2'-PHOSPHOTRANSFERASE; PHOSPHORYLATION; PURIFICATION; SEQUENCE AB The combined techniques of fast atom bombardment and tandem mass spectrometry have been applied to the structural determination of macrolide antibiotics. Major fragmentation processes in the protonated molecule involve cleavage at the glycosidic linkages while more extensive ring fragmentation is also noted in the spectra of the sodiated molecules. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. TOKYO COLL PHARM,DEPT CHEM ANAL,HACHIOJI,TOKYO 19203,JAPAN. TOKYO COLL PHARM,DEPT MICROBIOL,HACHIOJI,TOKYO 19203,JAPAN. RI Tomer, Kenneth/E-8018-2013 NR 39 TC 17 Z9 17 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD OCT 8 PY 1993 VL 49 IS 41 BP 9221 EP 9234 DI 10.1016/0040-4020(93)80009-I PG 14 WC Chemistry, Organic SC Chemistry GA MB076 UT WOS:A1993MB07600008 ER PT J AU OHAYON, J CHADWICK, R AZANCOTBENISTY, A ITO, Y AF OHAYON, J CHADWICK, R AZANCOTBENISTY, A ITO, Y TI DISTORTION OF THE LEFT-VENTRICLE BY THE RIGHT VENTRICLE SO COMPTES RENDUS DE L ACADEMIE DES SCIENCES SERIE II LA French DT Article ID MECHANICS AB A theoretical study, based on physiopathological observations, is presented to understand the effect of the right ventricle (RV) on the kinematics and dynamics of the left ventricle (LV). Our results show: (i) for a given geometry, rheology, and trans-septal pressure gradient, the shape of the LV is more sensitive to the RV pressure than the LV pressure, and (ii) the isotropic collagen matrix is one of the main determinants of the LV shape. C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENT PROGRAM,BETHESDA,MD 20892. HOP ROBERT DEBRE,EXPLORAT FONCT LAB,F-75019 PARIS,FRANCE. HIROSHIMA UNIV MED,DEPT INTERNAL MED 2,MINAMI KU,HIROSHIMA 734,JAPAN. RP OHAYON, J (reprint author), UNIV PARIS 12,MECAN PHYS LAB,AVE GEN DE GAULLE,F-94010 CRETEIL,FRANCE. NR 9 TC 0 Z9 0 U1 0 U2 0 PU GAUTHIER-VILLARS PI PARIS PA S P E S-JOURNAL DEPT, 120 BD ST GERMAIN, F-75006 PARIS, FRANCE SN 1251-8069 J9 CR ACAD SCI II PD OCT 7 PY 1993 VL 317 IS 7 BP 877 EP 884 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ME358 UT WOS:A1993ME35800004 ER PT J AU WINSLOW, JT HASTINGS, N CARTER, CS HARBAUGH, CR INSEL, TR AF WINSLOW, JT HASTINGS, N CARTER, CS HARBAUGH, CR INSEL, TR TI A ROLE FOR CENTRAL VASOPRESSIN IN PAIR BONDING IN MONOGAMOUS PRAIRIE VOLES SO NATURE LA English DT Article ID NEUROHYPOPHYSEAL PEPTIDES; MICROTUS-OCHROGASTER; SEXUAL-BEHAVIOR; MALE-RATS; OXYTOCIN; RECEPTOR; ANTAGONISTS; SYSTEM AB MONOGAMOUS social organization is characterized by selective affiliation with a partner, high levels of paternal behaviour and, in many species, intense aggression towards strangers for defence of territory, nest and mate1,2. Although much has been written about the evolutionary causes of monogamy, little is known about the proximate mechanisms for pair bonding in monogamous mammals2,3. The prairie vole, Microtus ochrogaster, is a monogamous, biparental rodent which exhibits long-term pair bonds characterized by selective affiliation (partner preference) and aggression4,5. Here we describe the rapid development of both selective aggression and partner preferences following mating in the male of this species. We hypothesized that either arginine-vasopressin (AVP) or oxytocin (OT), two nine-amino-acid neuropeptides with diverse forebrain projections, could mediate the development of selective aggression and affiliation. This hypothesis was based on the following observations: (1) monogamous and polygamous voles differ specifically in the distribution of forebrain AVP and OT receptors6,7; (2) AVP innervation in the prairie vole brain is sexually dimorphic and important for paternal behaviour8; (3) central AVP pathways have been previously implicated in territorial displays and social memory9,10; and (4) central OT pathways have been previously implicated in affiliative behaviours11. We now demonstrate that central AVP is both necessary and sufficient for selective aggression and partner preference formation, two critical features of pair bonding in the monogamous prairie vole. C1 NIMH,NEUROPHYSIOL LAB,POB 608,POOLESVILLE,MD 20837. UNIV MARYLAND,DEPT ZOOL,COLL PK,MD 20742. NR 27 TC 551 Z9 563 U1 19 U2 100 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 7 PY 1993 VL 365 IS 6446 BP 545 EP 548 DI 10.1038/365545a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MA661 UT WOS:A1993MA66100053 PM 8413608 ER PT J AU KIRSCHSTEIN, R AF KIRSCHSTEIN, R TI LARGEST UNITED-STATES CLINICAL-TRIAL EVER GETS UNDER WAY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP KIRSCHSTEIN, R (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 TC 5 Z9 5 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 6 PY 1993 VL 270 IS 13 BP 1521 EP 1521 DI 10.1001/jama.270.13.1521 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LZ334 UT WOS:A1993LZ33400005 PM 8371454 ER PT J AU ROGERS, AS AF ROGERS, AS TI RISK CALCULATIONS FOR HIV TRANSMISSION FROM INFECTED HEALTH-CARE WORKERS - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP ROGERS, AS (reprint author), NIH,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 6 PY 1993 VL 270 IS 13 BP 1544 EP 1544 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LZ334 UT WOS:A1993LZ33400015 ER PT J AU GELERNTER, J RISCH, N GOLDMAN, D AF GELERNTER, J RISCH, N GOLDMAN, D TI ALCOHOLISM AND THE D2-DOPAMINE RECEPTOR GENE - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIAAA,BETHESDA,MD. RP GELERNTER, J (reprint author), YALE UNIV,SCH MED,NEW HAVEN,CT 06510, USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 3 TC 3 Z9 3 U1 0 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 6 PY 1993 VL 270 IS 13 BP 1547 EP 1548 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA LZ334 UT WOS:A1993LZ33400024 ER PT J AU TEO, KK YUSUF, S FURBERG, CD AF TEO, KK YUSUF, S FURBERG, CD TI EFFECTS OF PROPHYLACTIC ANTIARRHYTHMIC DRUG-THERAPY IN ACUTE MYOCARDIAL-INFARCTION - AN OVERVIEW OF RESULTS FROM RANDOMIZED CONTROLLED TRIALS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID PRIMARY VENTRICULAR-FIBRILLATION; PLACEBO-CONTROLLED TRIAL; LOW-DOSE AMIODARONE; DOUBLE-BLIND; SECONDARY PREVENTION; ORAL MEXILETINE; HOSPITAL PHASE; TERM TREATMENT; ARRHYTHMIAS; LIDOCAINE AB Objective.-To investigate the effects of prophylactic therapy with antiarrhythmic agents on mortality in patients with myocardial infarction. Data Sources and Study Selection.-Data were obtained from all completed, published or unpublished, randomized, parallel controlled trials of antiarrhythmic agents, regardless of sample size. Investigators were contacted for data on patients excluded after randomization. Data Extraction.-Data on mortality were extracted by one author and confirmed where necessary by the others. Data Synthesis.-Mortality data from 138 trials on 98 000 patients were combined by the Yusuf-Peto adaptation of the Mantel-Haenszel method. There were 660 deaths among 11 712 patients allocated to receive class I agents and 571 deaths among 11 517 corresponding control patients (51 trials: odds ratio [OR], 1.14; 95% confidence interval [CI], 1.01 to 1.28; P=.03). Of 26 973 patients allocated to receive beta-blockers (class II agents), 1464 died compared with 1727 deaths among 26 295 control patients (55 trials: OR, 0.81; 95% CI, 0.75 to 0.87; P=.00001). Of 778 patients allocated to receive amiodarone (a class III agent), 77 died compared with 101 deaths in 779 control patients (eight trials: OR, 0.71; 95% CI, 0.51 to 0.97; P=.03). There were 982 deaths in 10 154 patients allocated to receive a class IV agent (calcium channel blockers) and 949 deaths in 10 188 control patients (24 trials: OR, 1.04; 95% CI, 0.95 to 1.14; P=.41). Conclusions.-The routine use of class I antiarrhythmic agents after myocardial infarction is associated with increased mortality. Beta-blockers have been conclusively demonstrated to reduce mortality. The limited data on amiodarone appear promising. Data on calcium channel blockers remain unpromising. C1 NHLBI, CLIN TRIALS BRANCH, BETHESDA, MD 20892 USA. MCMASTER UNIV, DIV CARDIOL, HAMILTON L8S 4L8, ONTARIO, CANADA. WAKE FOREST UNIV, BOWMAN GRAY SCH MED, DEPT PUBL HLTH SCI, WINSTON SALEM, NC 27103 USA. RP TEO, KK (reprint author), UNIV ALBERTA, DIV CARDIOL, 2C2 WALTER MACKENZIE CTR, EDMONTON T6G 2R7, AB, CANADA. NR 89 TC 403 Z9 413 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 6 PY 1993 VL 270 IS 13 BP 1589 EP 1595 DI 10.1001/jama.270.13.1589 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA LZ334 UT WOS:A1993LZ33400034 PM 8371471 ER PT J AU PLUDA, JM SHAY, LE FOLI, A TANNENBAUM, S COHEN, PJ GOLDSPIEL, BR ADAMO, D COOPER, MR BRODER, S YARCHOAN, R AF PLUDA, JM SHAY, LE FOLI, A TANNENBAUM, S COHEN, PJ GOLDSPIEL, BR ADAMO, D COOPER, MR BRODER, S YARCHOAN, R TI ADMINISTRATION OF PENTOSAN POLYSULFATE TO PATIENTS WITH HUMAN IMMUNODEFICIENCY VIRUS-ASSOCIATED KAPOSI-SARCOMA SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Note ID FIBROBLAST GROWTH-FACTOR; LONG-TERM CULTURE; ANTI-HIV AGENT; TUMOR-GROWTH; SULFATED POLYSACCHARIDES; POTENT INHIBITORS; DEXTRAN SULFATE; CELLS; AIDS; HEPARIN AB Background: Neovascularization induced by basic fibroblast growth factor (basic FGF) or FGF-like cytokines is thought to play a substantial role in the pathogenesis of human immunodeficiency virus (HIV)-associated Kaposi's sarcoma. Pentosan polysulfate has been shown to inhibit basic FGF and FGF-like dependent tumor growth both in vitro and in vivo. Moreover, it has been found to inhibit the growth of Kaposi's sarcoma-derived spindle cells in vitro. These observations suggested that pentosan polysulfate might be worth exploring as a potential agent for the treatment of Kaposi's sarcoma. Purpose: The purpose of this phase I clinical trial was to determine the maximum tolerated dose of pentosan polysulfate in patients with HIV-associated Kaposi's sarcoma and whether or not this compound had activity against this neoplasm. Methods: Sixteen HIV-seropositive patients with Kaposi's sarcoma received pentosan polysulfate via continuous venous infusion for 3-6 weeks and then received a subcutaneous dose three times per week. Three different doses of pentosan polysulfate were administered: 2 mg/kg per day by infusion followed by 2 mg/kg per dose given subcutaneously (six patients), 3 mg/kg per day by infusion followed by 3 mg/kg per dose given subcutaneously (five patients), and 4 mg/kg per day by infusion followed by 4 mg/kg per dose given subcutaneously (five patients). Five of the 16 patients in the study also received injections of 1 mg of pentosan polysulfate into two different lesions two times a week for 3 weeks, followed by intralesional therapy once weekly. After receiving pentosan polysulfate for 6 weeks, patients were administered 100 mg zidovudine (AZT) orally every 4 hours in conjunction with pentosan polysulfate. Results: The maximally tolerated dose of pentosan polysulfate given by continuous venous infusion was found to be 3 mg/kg per day. No patient had an objective clinical antitumor response to either systemic or intralesional pentosan polysulfate administration; however, three patients had stable Kaposi's sarcoma for 3-27 weeks. No statistically significant effect on CD4 cells or serum HIV p24 antigen was noted during pentosan polysulfate administration. Dose-limiting toxic effects were characterized by anticoagulation and thrombocytopenia and were reversible. Conclusion: Pentosan polysulfate was well tolerated in this patient population. However, no objective tumor response or evidence of anti-HIV activity was noted; therefore, no claim of activity can be made in this trial. Implication: Continued investigation into the use of angiogenesis inhibitors with improved activity and toxicity profiles or different mechanisms of action is warranted. C1 NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,MED BRANCH,BETHESDA,MD 20892. NCI,DIV CANC BIOL DIAGNOSIS & CTR,INTRAMURAL RES PROGRAM,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NCI,OFF DIRECTOR,BETHESDA,MD 20892. NR 48 TC 53 Z9 53 U1 1 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 6 PY 1993 VL 85 IS 19 BP 1585 EP 1592 DI 10.1093/jnci/85.19.1585 PG 8 WC Oncology SC Oncology GA LZ632 UT WOS:A1993LZ63200014 PM 7692072 ER PT J AU MARTIN, JL REED, GF POHL, LR AF MARTIN, JL REED, GF POHL, LR TI ASSOCIATION OF ANTI-58 KDA ENDOPLASMIC-RETICULUM ANTIBODIES WITH HALOTHANE HEPATITIS SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID PHOSPHOLIPASE-C-ALPHA; PROTEIN-DEGRADATION; RAT-LIVER; SERA; NEOANTIGENS; METABOLITE; ANTIGENS AB We recently showed that when rats were administered the inhalation anesthetic halothane, a 58 kDa liver endoplasmic reticulum protein became covalently trifluoroacetylated by the trifluoroacetyl chloride metabolite of halothane. Although the 58 kDa protein showed 99% identity to that of the deduced amino acid sequence of a cDNA reported to correspond to phosphatidylinositol-specific phospholipase C-alpha, it did not have phosphatidylinositol-specific phospholipase C activity. It was concluded that the reported cDNA of phosphatidylinositol-specific phospholipase C-alpha actually encoded for the 58 kDa endoplasmic reticulum protein of unknown function. Other researchers have come to the same conclusion and have shown that the 58 kDa protein has protein disulfide-isomerase and protease activities. We now report that patients with halothane hepatitis have serum antibodies that react with both purified trifluoroacetylated and native rat liver 58 kDa proteins. These results suggest that when patients are exposed to halothane a human liver orthologue of the rat liver trifluoroacetylated-58 kDa protein is formed. In certain patients, this protein may become immunogenic and lead to the formation of specific antibodies and or specific T-cells, which may react with both trifluoroacetylated and native 58 kDa proteins, and ultimately be responsible, at least in part, for the hepatitis caused by halothane. C1 NIAID,EPIDEMIOL & BIOMETRY BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS MED INST,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21205. RP MARTIN, JL (reprint author), NHLBI,CHEM PHARMACOL LAB,BLDG 10,ROOM 8N 115,BETHESDA,MD 20892, USA. NR 20 TC 30 Z9 30 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD OCT 5 PY 1993 VL 46 IS 7 BP 1247 EP 1250 DI 10.1016/0006-2952(93)90474-B PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MD261 UT WOS:A1993MD26100019 PM 8216376 ER PT J AU BRZOVIC, PS HYDE, CC MILES, EW DUNN, MF AF BRZOVIC, PS HYDE, CC MILES, EW DUNN, MF TI CHARACTERIZATION OF THE FUNCTIONAL-ROLE OF A FLEXIBLE LOOP IN THE ALPHA-SUBUNIT OF TRYPTOPHAN SYNTHASE FROM SALMONELLA-TYPHIMURIUM BY RAPID-SCANNING, STOPPED-FLOW SPECTROSCOPY AND SITE-DIRECTED MUTAGENESIS SO BIOCHEMISTRY LA English DT Article ID ULTRAVIOLET VISIBLE SPECTROSCOPY; ESCHERICHIA-COLI; BIENZYME COMPLEX; TRIOSEPHOSPHATE ISOMERASE; BETA-SUBUNIT; L-SERINE; 3-DIMENSIONAL STRUCTURE; ALLOSTERIC INTERACTIONS; ALPHA-2-BETA-2 COMPLEX; SUBSTRATE-SPECIFICITY AB The function of a flexible loop (loop 6) in the alpha-subunit from the tryptophan synthase alpha2beta2 bienzyme complex has been investigated utilizing rapid-scanning (RSSF) and single-wavelength (SWSF) stopped-flow spectroscopies. Loop 6 is an extended sequence of residues which connects beta-strand 6 with, alpha-helix 6 in the beta/alpha-barrel fold of the alpha-subunit. Substitution of Leu for Arg179 near the base of loop 6 does not significantly affect either the association of the alpha- and beta-subunits to form the bienzyme complex or the kinetics of the reaction of indole with L-serine (L-Ser) to form L-tryptophan (L-Trp), the process catalyzed by the wild-type beta-subunit [Kawasaki, H., Bauerle, R., Zon, G., Ahmed, S., & Miles, E. W. (1987) J. Biol. Chem. 262, 10678-10683]. However, the alpha-subunit-specific ligand glycerol phosphate (GP), which is an inhibitor of the wild-type beta-reaction, is a much less effective inhibitor of the alphaR179L-catalyzed beta-reaction. Equilibrium titration studies show that the affinity of GP for the alpha-site when either L-Ser or glycine is bound at the beta-site has been reduced by nearly 100- and 200-fold, respectively. SWSF analysis of the reaction of IGP and L-Ser to form L-Trp catalyzed by the bienzyme complex revealed a 15-fold reduction in the binding affinity of the alpha-site substrate 3-indole-D-glycerol 3'-phosphate (IGP) in the reaction catalyzed by the alphaR179L mutant as compared to the wild-type enzyme. These studies show that loop 6 is important both for ligand binding to the alpha-site and for the ligand-induced conformational transition of the alpha-subunit from an ''open'' to a ''closed'' structure. Modeling studies, based on extensive structural homology of the alpha-subunit with the glycolytic enzyme triosephosphate isomerase (TIM), predict that closure of loop 6 induced by ligand binding at the alpha-active site would effectively sequester the bound substrate from the solvent and trap indole, produced from the cleavage of IGP, within the confines of the bienzyme complex. This conformational transition would promote the diffusion of indole to the beta-active site via the interconnecting tunnel and would help ensure the close coordination of alpha- and beta-subunit catalytic activities. C1 UNIV CALIF RIVERSIDE, DEPT BIOCHEM 015, RIVERSIDE, CA 92521 USA. NIAMSD, BETHESDA, MD 20892 USA. NIADDKD, BIOCHEM PHARMACOL LAB, BETHESDA, MD 20892 USA. NR 41 TC 66 Z9 66 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 5 PY 1993 VL 32 IS 39 BP 10404 EP 10413 DI 10.1021/bi00090a016 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MA664 UT WOS:A1993MA66400016 PM 8399184 ER PT J AU AHUJA, SK MURPHY, PM AF AHUJA, SK MURPHY, PM TI MOLECULAR PIRACY OF MAMMALIAN INTERLEUKIN-8 RECEPTOR TYPE-B BY HERPESVIRUS SAIMIRI SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID FORMYL PEPTIDE RECEPTOR; XENOPUS OOCYTES REQUIRES; OPEN READING FRAME; FUNCTIONAL EXPRESSION; PROTEIN; VIRUS; ENCODES; TRANSFORMATION; ANGIOGENESIS; INFECTION AB Viruses are known to acquire and modify the genes of their hosts to attain a survival advantage in the host environment. Herpesvirus saimiri (HVS) is a T-lymphotropic virus that causes fatal lymphoproliferative diseases in several non-human primates. The gene ECRF3 of HVS was most likely acquired from a primate host. ECRF3 encodes a putative seven-transmembrane-domain receptor that is remotely related (approximately 30% amino acid identity) to the known mammalian alpha and beta chemokine receptors, namely interleukin-8 receptor (IL8R) types A and B and the MIP-1alpha/RANTES receptor, respectively. Chemokines regulate the trafficking, activation, and, in some cases, proliferation of myeloid and lymphoid cell types. We now show that ECRF3 encodes a functional receptor for the alpha chemokines IL-8, GRO/melanoma growth stimulatory activity (MGSA), and NAP-2 but not for beta chemokines, a specificity identical to that of IL8RB. Paradoxically, IL8RA shares 77% amino acid identity with IL8RB but is not a receptor for GRO/MGSA or NAP-2. This is the first functional characterization of a viral seven-transmembrane-domain receptor. It suggests a novel role for alpha chemokines in the pathogenesis of HVS infection by transmembrane signaling via the product of ECRF3. C1 NIAID,HOST DEFENSES LAB,BLDG 10,RM 11N113,BETHESDA,MD 20892. NR 42 TC 204 Z9 206 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 5 PY 1993 VL 268 IS 28 BP 20691 EP 20694 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MA288 UT WOS:A1993MA28800003 PM 8407886 ER PT J AU STEFANOVA, I CORCORAN, ML HORAK, EM WAHL, LM BOLEN, JB HORAK, ID AF STEFANOVA, I CORCORAN, ML HORAK, EM WAHL, LM BOLEN, JB HORAK, ID TI LIPOPOLYSACCHARIDE INDUCES ACTIVATION OF CD14-ASSOCIATED PROTEIN-TYROSINE KINASE P53/56LYN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID STIMULATED HUMAN MONOCYTES; MONOCLONAL-ANTIBODIES; SRC FAMILY; CD14; MOLECULES AB Bacterial lipopolysaccharide (LPS) induces a pleiotropic activation of the immune system which might subsequently result in septic shock. One of the cell surface receptors for LPS is the glycophosphatidylinositol-anchored protein CD14. Binding of LPS to CD14 induces production of lymphokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), IL-6, and IL-8, and CD14 is subsequently released from the cell surface. However, the mechanism of signaling via CD14 is still not known. We report here that protein tyrosine kinase (PTK) p56lyn is coupled to the LPS receptor CD14 in human monocytes. LPS rapidly activates CD14-associated p56lyn simultaneously with PTKs p58hck and p59c-fgr. Inhibition of PTKs by herbimycin A completely blocks LPS-induced down-modulation of CD14 and production of TNF-alpha and IL-1. These data suggest a critical role of PTKs in the LPS/CD14-mediated signal transduction pathway in human monocytes. C1 NIH,INST DENT RES,IMMUNOL LAB,BETHESDA,MD 20892. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,DEPT MOLEC BIOL,PRINCETON,NJ 08543. RP STEFANOVA, I (reprint author), NCI,DIV CANC BIOL DIAG & CTR,METAB BRANCH,BLDG 10-4N115,BETHESDA,MD 20892, USA. NR 19 TC 288 Z9 288 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 5 PY 1993 VL 268 IS 28 BP 20725 EP 20728 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MA288 UT WOS:A1993MA28800012 PM 7691802 ER PT J AU SARTOR, O ROBBINS, KC AF SARTOR, O ROBBINS, KC TI SUBSTRATE-SPECIFICITY FOR NORMAL BUT NOT MUTATIONALLY ACTIVATED VARIANTS OF SRC FAMILY KINASES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE KINASES; SH3 DOMAINS; MONOCLONAL-ANTIBODIES; SIGNAL TRANSDUCTION; STABLE ASSOCIATION; CATALYTIC DOMAINS; PP60SRC SUBSTRATE; CELLULAR PROTEINS; CELLS; GENE AB Although structural features and expression patterns of the src family of tyrosine kinases have been extensively analyzed, there are no direct comparative studies of the putative protein substrates that are tyrosine-phosphorylated by the normal cellular versions of these enzymes. In this report, we have expressed normal and enzymatically activated versions of the fyn, fgr, and src translational products by transfection of appropriate cDNAs into mouse fibroblasts. Because the same parental cell line was used for all transfections, each enzyme was expressed in a similar milieu of potential in vivo substrates. After verification of appropriate expression from each transfected cDNA and assessment of relative transforming potency, a series of putative protein substrates was specifically assayed for expression and tyrosine phosphorylation. Our data indicate that the normal src family kinases display some degree of substrate specificity but that specificity is diminished when these enzymes are constitutively activated. In the course of these studies, tyrosine-phosphorylated proteins were noted to coimmunoprecipitate with some of these putative in vivo substrates. Some of these coimmunoprecipitating proteins have been reported previously, whereas others, such as the presence of p59fyn in anti-p80/85 immunoprecipitates, are heretofore undescribed. C1 NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. RP SARTOR, O (reprint author), NCI,CLIN PHARMACOL BRANCH,RM 12N226,BLDG 10,BETHESDA,MD 20892, USA. NR 34 TC 14 Z9 14 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 5 PY 1993 VL 268 IS 28 BP 21014 EP 21020 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MA288 UT WOS:A1993MA28800059 PM 7691803 ER PT J AU GORBEA, CM MARCHAND, P JIANG, WP COPELAND, NG GILBERT, DJ JENKINS, NA BOND, JS AF GORBEA, CM MARCHAND, P JIANG, WP COPELAND, NG GILBERT, DJ JENKINS, NA BOND, JS TI CLONING, EXPRESSION, AND CHROMOSOMAL LOCALIZATION OF THE MOUSE MEPRIN BETA-SUBUNIT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GENETIC-LINKAGE MAP; KIDNEY; SEQUENCES; DNA; METALLOENDOPEPTIDASES; ASTACIN; REVEALS; PROTEIN; ENZYME; ALPHA AB Meprins are plasma membrane homo- or hetero-oligomeric metalloendopeptidases that contain glycosylated alpha and/or beta subunits. This paper reports the cloning and sequencing of the mouse kidney beta subunit. The primary translation product is composed of 704 amino acids which includes a transient signal sequence of 20 amino acids at the NH2 terminus. The protease domain (Asn-63 to Leu-260) contains the putative zinc-binding motif characteristic of metalloendopeptidases of the ''astacin family.'' The COOH terminus contains an epidermal growth factor-like domain, a potential membrane-spanning domain, and an additional 26 amino acids. The beta subunit has an overall 42% identity to the alpha subunit, however, a 56-amino acid segment near the COOH terminus of alpha is missing in beta, and the putative transmembrane and cytoplasmic domains of the subunits share no significant sequence similarity. NH2-terminal analyses of detergent-solubilized mature forms revealed that, unlike alpha, the prosequence (Leu-21 to Lys-62) is not removed from the beta subunit. Northern blot analysis revealed a 2.5-kilobase message for the beta subunit in the kidney and intestine of C57BL/6 and C3H/He mice. The gene for the beta subunit was localized to mouse chromosome 18. These studies indicate that alpha and beta probably derived from a common ancestral gene, but have evolved so that their genes are on two different chromosomes, and their tissue-specific expression and post-translational processing differ. C1 PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT BIOL CHEM,HERSHEY,PA 17033. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ADV BIOSCI LABS INC,BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101]; NIDDK NIH HHS [DK 19691] NR 34 TC 69 Z9 71 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 5 PY 1993 VL 268 IS 28 BP 21035 EP 21043 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MA288 UT WOS:A1993MA28800062 PM 8407940 ER PT J AU LEE, CW PARK, DJ LEE, KH KIM, CG RHEE, SG AF LEE, CW PARK, DJ LEE, KH KIM, CG RHEE, SG TI PURIFICATION, MOLECULAR-CLONING, AND SEQUENCING OF PHOSPHOLIPASE-C-BETA-4 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ROD OUTER SEGMENTS; LIGHT-MEDIATED BREAKDOWN; INOSITOL-TRISPHOSPHATE; BOVINE BRAIN; BETA-GAMMA; COMPLETE CDNA; C ISOZYMES; G-PROTEINS; DROSOPHILA; SUBUNITS AB We have characterized inositol phospholipid-specific phospholipase C (PLC) isozymes in bovine retina. Chromatography of a retinal homogenate on a heparin column partially resolved six peaks of PLC activity, which differed in their relative selectivities for the substrates phosphatidyl 4,5-bisphosphate (PIP2) and phosphatidylinositol (PI). Five of the peaks were shown to correspond to the known PLC isozymes PLC-beta1, PLC-beta3, PLC-gamma1, PLC-delta1, and PLC-delta2. PLC-beta1, PLC-beta3, PLC-gamma1, and PLC-delta1 in the retinal fractions were identified by immunoblotting with isozyme-specific antibodies, and PLC-delta2 was identified by direct sequencing of tryptic peptides. PLC-gamma2 and PLC-beta2 were not detectable by immunoblot analysis. In addition to five of the seven mammalian PLC isozymes identified to date, bovine retina contained a previously unidentified PLC, which exhibited the highest selectivity for PIP2 over PI. The new PLC was purified from a retinal particulate fraction to yield a preparation that contained a major protein band with an apparent molecular mass of 130 kDa on SDS-polyacrylamide gels. Sequence analysis of 12 tryptic peptides derived from the 130-kDa protein suggested that the primary structure of the new PLC is similar to those members of beta-type PLC isozymes, especially to that of PLC-norpA, which was originally identified in Drosophila eye. The new enzyme was thus named PLC-beta4. A search of a rat brain cDNA library with the polymerase chain reaction and oligonucleotide primers based on common PLC amino acid sequences resulted in the cloning of a rat brain cDNA corresponding to a previously uncharacterized PLC. The cDNA encoded a putative polypeptide of 1176 amino acids, with a calculated molecular mass of 134,532 daltons, that contained the sequences of all 12 tryptic peptides of PLC-beta4. Furthermore, the deduced amino acid sequence of the encoded protein was more related to PLC-norpA than to any of the three mammalian PLC-beta isozymes. These results suggest that the brain cDNA encodes PLC-beta4, which is likely a mammalian homolog of PLC-norpA. C1 NHLBI,BIOCHEM LAB,9000 ROCKVILLE PIKE,BLDG 3,RM 122,BETHESDA,MD 20892. RI Park, Do-Joon/J-2736-2012 NR 45 TC 110 Z9 112 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 5 PY 1993 VL 268 IS 28 BP 21318 EP 21327 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MA288 UT WOS:A1993MA28800098 PM 8407970 ER PT J AU TAKIMOTO, CH VOELLER, DB STRONG, JM ANDERSON, L CHU, E ALLEGRA, CJ AF TAKIMOTO, CH VOELLER, DB STRONG, JM ANDERSON, L CHU, E ALLEGRA, CJ TI EFFECTS OF 5-FLUOROURACIL SUBSTITUTION ON THE RNA CONFORMATION AND IN-VITRO TRANSLATION OF THYMIDYLATE SYNTHASE MESSENGER-RNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RESISTANT KB CELLS; DIHYDROFOLATE-REDUCTASE; CARCINOMA-CELLS; CYTO-TOXICITY; RIBOSOMAL-RNA; HUMAN-BREAST; INHIBITION; COMBINATION; ACID AB In vitro transcribed thymidylate synthase (TS) mRNA which is 100% substituted with 5-fluorouracil (FUra) was analyzed for changes in mRNA secondary structure, for alterations in translational efficiency, and for evidence of translational miscoding in vitro. FUra substitution in TS mRNA results in an altered migration pattern in non-denaturing RNA gels and in decreased hyperchromicity in RNA melting temperature studies, consistent with a change in mRNA secondary structure. However, no change in the translational efficiency of FUra-substituted TS mRNA is seen compared to control TS mRNA in either rabbit reticulocyte lysate or wheat germ extract in vitro translation systems. Analysis of the in vitro translation product of FUra-substituted TS mRNA by Western immunoblotting, isoelectric focusing, 5-fluoro-2'-deoxyuridine 5'-monophosphate binding, and TS catalytic activity experiments shows no difference compared to control TS mRNA. We conclude that the in vitro translation products of FUra-substituted and control TS mRNA are identical. Our findings do not support the hypothesis that changes in the mRNA template are responsible for the RNA-directed cytotoxicity of FUra. C1 US FDA, CTR DRUG EVALUAT & RES, DIV CLIN PHARMACOL, OFF RES RESOURCES, ROCKVILLE, MD 20850 USA. RP TAKIMOTO, CH (reprint author), NATL NAVAL MED CTR, NCI,DIV CANC TREATMENT,MED ONCOL BRANCH,BLDG 8, RM 5101, BETHESDA, MD 20814 USA. NR 31 TC 19 Z9 19 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 5 PY 1993 VL 268 IS 28 BP 21438 EP 21442 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MA288 UT WOS:A1993MA28800115 PM 8407987 ER PT J AU GRONENBORN, AM CLORE, GM AF GRONENBORN, AM CLORE, GM TI IDENTIFICATION OF THE CONTACT SURFACE OF A STREPTOCOCCAL PROTEIN G-DOMAIN COMPLEXED WITH A HUMAN FC FRAGMENT SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Note DE PROTEIN-G IGG BINDING DOMAIN; HUMAN IGGFC COMPLEX; SOLUTION STRUCTURE; HETERONUCLEAR NMR ID IMMUNOGLOBULIN-BINDING DOMAIN; STAPHYLOCOCCUS-AUREUS; CRYSTAL-STRUCTURE; NMR; SPECTROSCOPY RP GRONENBORN, AM (reprint author), NIDDKD,CHEM PHYS LAB,BLDG 5,BETHESDA,MD 20814, USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 17 TC 84 Z9 85 U1 0 U2 4 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 5 PY 1993 VL 233 IS 3 BP 331 EP 335 DI 10.1006/jmbi.1993.1514 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MA028 UT WOS:A1993MA02800001 PM 8411147 ER PT J AU LEHNHERR, H MAGUIN, E JAFRI, S YARMOLINSKY, MB AF LEHNHERR, H MAGUIN, E JAFRI, S YARMOLINSKY, MB TI PLASMID ADDICTION GENES OF BACTERIOPHAGE-P1 - DOC, WHICH CAUSES CELL-DEATH ON CURING OF PROPHAGE, AND PHD, WHICH PREVENTS HOST DEATH WHEN PROPHAGE IS RETAINED SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE PHAGE-P1; POST-SEGREGATIONAL KILLING; PLASMID STABILIZATION ID SITE-SPECIFIC RECOMBINATION; 42.84-43.6 F-SEGMENT; SOS-INDUCING SIGNAL; SEX FACTOR-F; ESCHERICHIA-COLI; DNA-REPLICATION; STABLE MAINTENANCE; CCDB PROTEIN; INDUCTION; IDENTIFICATION C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 72 TC 157 Z9 163 U1 2 U2 12 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD OCT 5 PY 1993 VL 233 IS 3 BP 414 EP 428 DI 10.1006/jmbi.1993.1521 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MA028 UT WOS:A1993MA02800008 PM 8411153 ER PT J AU GONZALEZ, FJ AF GONZALEZ, FJ TI MOLECULAR-BIOLOGY OF HUMAN XENOBIOTIC-METABOLIZING CYTOCHROMES-P450 - ROLE OF VACCINIA VIRUS CDNA EXPRESSION IN EVALUATING CATALYTIC FUNCTION SO TOXICOLOGY LA English DT Article; Proceedings Paper CT MEETING ON APPLICATION OF CELLULAR SYSTEMS IN DRUG METABOLISM AND TOXICITY STUDIES CY JUL 21-24, 1991 CL OTZENHAUSEN, SAARLAND, GERMANY SP STIFT VOLKSWAGENWERK, BAYER, GOEDECKE, HOECHST, PIERRE FABRE MEDICAMENT LAB, RHONE POULENC RORER, ROUSSELLL UCLAF HO OTZENHAUSEN DE AFLATOXIN-B1; CYTOCHROME-P450; VACCINIA VIRUS ID HUMAN-LIVER-MICROSOMES; AMINO-ACID SEQUENCE; DIRECTED EXPRESSION; NADPH-CYTOCHROME-P450 REDUCTASE; COMPLEMENTARY-DNA; STEROID-HORMONES; MESSENGER-RNAS; GENE SUBFAMILY; CYTOCHROME-P-450; IDENTIFICATION AB Mammalian xenobiotic-metabolizing cytochromes P450s are membrane-bound enzymes that use O2 and electrons from NADPH to oxidize their substrates. For most chemical substrates, stable metabolites are produced that are destined for further metabolism and elimination from the cell. These enzymes are also capable of metabolically-converting promutagens and procarcinogens to their active proximate metabolites that can kill and transform cells. The xenobiotic-metabolizing P450s reside with three distinct families of the large P450 superfamily. To study the catalytic activities of P450s, particularly human P450s that cannot be easily purified, a cDNA expression system was developed using vaccinia virus. P450 cDNAs incorporated into this lytic virus are efficiently expressed into catalytically-active enzymes that can be used to determine substrate specificities of specific human P450s forms. Activation of the hepatocarcinogen aflatoxin E1 was determined using a sseries of vaccinia virus-expressed P450s establishing that it is metabolically-activated to a DnA-binding derivative by serveral human P450 forms, albeit to differing extents. RP GONZALEZ, FJ (reprint author), NCI,MOLEC CARCINOGENESIS LAB,BLDG 37,ROOM 3E24,BETHESDA,MD 20892, USA. NR 36 TC 11 Z9 11 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD OCT 5 PY 1993 VL 82 IS 1-3 BP 77 EP 88 DI 10.1016/0300-483X(93)90061-V PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA MC363 UT WOS:A1993MC36300007 PM 8236283 ER PT J AU CRESPI, CL LANGENBACH, R PENMAN, BW AF CRESPI, CL LANGENBACH, R PENMAN, BW TI HUMAN CELL-LINES, DERIVED FROM AHH-1 TK+/- HUMAN LYMPHOBLASTS, GENETICALLY-ENGINEERED FOR EXPRESSION OF CYTOCHROMES-P450 SO TOXICOLOGY LA English DT Article; Proceedings Paper CT MEETING ON APPLICATION OF CELLULAR SYSTEMS IN DRUG METABOLISM AND TOXICITY STUDIES CY JUL 21-24, 1991 CL OTZENHAUSEN, SAARLAND, GERMANY SP STIFT VOLKSWAGENWERK, BAYER, GOEDECKE, HOECHST, PIERRE FABRE MEDICAMENT LAB, RHONE POULENC RORER, ROUSSELLL UCLAF HO OTZENHAUSEN DE CDNA EXPRESSION; EXTRACHROMOSOMAL VECTORS; PROCARCINOGEN; PROMUTAGEN ID ARYL-HYDROCARBON HYDROXYLASE; HUMAN-LIVER; METABOLIC-ACTIVATION; CYTOCHROME-P-450 ENZYMES; XENOBIOTIC METABOLISM; GENE MUTATION; AFLATOXIN-B1; BIOACTIVATION; CDNA; MUTAGENICITY AB We are developing a panel of human B lymphoblastoid cells which have been engineered to express specific human cDNAs for cytochrome P450 and other xenobiotic metabolizing enzymes. The recipient cells are of a human B lymphoblastoid cell line, designated AHH-1 TK+/-. These cells are transfected using two extrachromosomal vectors both containing OriP sequences derived from Epstein Barr virus but containing independent means of selection in mammalian cells. Using this system, the level of cDNA expression is nearly always stable and consistent from one transfection to another. Thus, once the level of expression has been characterized, cell lines with potentially interesting combinations of xenobiotic-metabolizing enzymes can be predictably developed. cDNAs encoding the following human enzymes have been expressed in this system: CYP1A1, CYP1A2, CYP2A6, CYP2B8, CYP2C6, CYP2C9, CYP2D6, CYP2E1, CYP3A4 and microsomal epoxide hydrolase. We have expressed all of these enzymes individually and have developed cell lines which express combinations of the xenobiotic metabolizing enzymes. The expression of multiple enzymes is important for generalized use of engineered cells as toxicology screening tools. We have primarily used the cell lines in applications to toxicology focusing on procarcinogen activation as detected in assays for the induction of gene locus mutations. In this chapter we discuss the general properties of the system and applications to toxicology testing. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP CRESPI, CL (reprint author), GENTEST CORP,6 HENSHAW ST,WOBURN,MA 01801, USA. NR 35 TC 63 Z9 64 U1 0 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD OCT 5 PY 1993 VL 82 IS 1-3 BP 89 EP 104 DI 10.1016/0300-483X(93)90062-W PG 16 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA MC363 UT WOS:A1993MC36300008 PM 8236284 ER PT J AU SALLIE, R AF SALLIE, R TI A CASE OF ACUTE HEPATITIS-E IN VICTORIA SO MEDICAL JOURNAL OF AUSTRALIA LA English DT Letter ID NON-B HEPATITIS; NON-A RP SALLIE, R (reprint author), NIH,LIVER DIS SECT,BETHESDA,MD 20892, USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU AUSTRALASIAN MED PUBL CO LTD PI SYDNEY PA LEVEL 1, 76 BERRY ST, SYDNEY NSW 2060, AUSTRALIA SN 0025-729X J9 MED J AUSTRALIA JI Med. J. Aust. PD OCT 4 PY 1993 VL 159 IS 7 BP 494 EP 494 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MA645 UT WOS:A1993MA64500036 PM 8412937 ER PT J AU MARTIN, SE ANNAN, S FORST, B AF MARTIN, SE ANNAN, S FORST, B TI THE SPECIAL DETERRENT EFFECTS OF A JAIL SANCTION ON 1ST-TIME DRUNK DRIVERS - A QUASI-EXPERIMENTAL STUDY SO ACCIDENT ANALYSIS AND PREVENTION LA English DT Article ID DRINKING AB This study examines the special deterrent effects of alternative sanctions on first-time offenders convicted of driving while intoxicated (DWI). It uses a quasi-experimental design based on the fact that in Hennepin County, Minnesota, some judges did not comply with the judicial policy that mandated a two-day jail sentence for all first-time DWI offenders. Data were collected on all drunk driving cases adjudicated by two judges during an 11-month period. One judge was known to sentence few first offenders to jail; the other was reputed to sentence virtually all first offenders to jail. Of the 383 offenders sentenced by the two judges, 60 were reconvicted within the 23-month follow-up period. Using judge as an indirect measure of the jail sanction, we found no statistically significant difference in the recidivism rates of persons sentenced by the ''jail'' and ''no jail'' judges. Nor did the sanction have a direct effect. After statistically controlling for offender characteristics and prior traffic record, there was no significant difference between those sentenced to a fine (large or small) with no jail and those who were given a two-day jail sentence plus a small fine. Thus, a two-day jail stay is found to be no more effective in deterring subsequent drunk driving by convicted first offenders than an alternative monetary sanction. C1 POLICE FDN,WASHINGTON,DC 20037. AMERICAN UNIV,DEPT JUSTICE LAW & SOC,WASHINGTON,DC 20016. RP MARTIN, SE (reprint author), NIAA,PREVENT RES BRANCH,ROCKVILLE,MD 20857, USA. NR 22 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 0001-4575 J9 ACCIDENT ANAL PREV JI Accid. Anal. Prev. PD OCT PY 1993 VL 25 IS 5 BP 561 EP 568 DI 10.1016/0001-4575(93)90008-K PG 8 WC Ergonomics; Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary; Transportation SC Engineering; Public, Environmental & Occupational Health; Social Sciences - Other Topics; Transportation GA LU320 UT WOS:A1993LU32000008 PM 8397659 ER PT J AU MARIN, G MALOZOWSKI, SN BARNES, K SOUTHERS, J CRISTIANO, A CASSORLA, F AF MARIN, G MALOZOWSKI, SN BARNES, K SOUTHERS, J CRISTIANO, A CASSORLA, F TI ENDOCRINE PROFILE OF CATCH-UP GROWTH IN THE CYNOMOLGUS MONKEY SO ACTA ENDOCRINOLOGICA LA English DT Article ID SOMATOMEDIN-C; RADIOIMMUNOASSAY; SECRETION; HORMONE; SERUM AB We studied catch-up growth following withdrawal of glucocorticoid administration in seven intact prepubertal cynomolgus monkeys. To reduce stress during blood sampling, a vascular access port was implanted subcutaneously in each animal for the duration of the study. After a baseline observation period of 50 weeks, the monkeys received injections of dexamethasone at a dose of 100 mug.kg-1.day-1 for 15 weeks. Growth velocity was monitored every 3 weeks by measuring lower leg length and body weight. Spontaneous serum growth hormone (GH) concentrations and GH levels after insulin and L-dopa stimulation, as well as serum insulin-like growth factor I (IGF-I) and plasma thyrotropin, triiodothyronine and thyroxine, were measured during the study. Differences between animals were analyzed by repeated measures analysis of variance and Student's paired t-test. Mean +/- SEM growth velocity (mm/3 weeks) decreased from 0.90 +/- 0.08 during the baseline period to 0.29 +/- 0.07 (p<0.001) during the period of growth retardation, and increased to 1.23 +/- 0.2 (p<0.001) during the period of catch-up growth. Spontaneous GH and peak GH levels following insulin did not show any significant variation during the study. Peak GH during the L-dopa test decreased from 15.4 +/- 3.2 mug/l during the baseline period to 6.2 +/- 2.4 mug/l during the period of growth retardation (p < 0.05), and increased to 23.0 +/- 5.9 mug/l during the period of catch-up growth (p < 0.05). Serum IGF-I levels were 3.0 +/- 1.0 mU/l during the baseline period. increased to 9.5 +/- 1.3 mU/l (p < 0.05) during the period of dexamethasone administration and decreased to 6.1 +/- 1.0 mU/l during catch-up. Plasma thyroxine and triiodothyronine levels did not vary during the study, whereas thyrotropin decreased during the period of growth retardation. We conclude that GH secretion increases after L-dopa during catch-up growth in this primate model, suggesting that GH may play a role in the accelerated growth observed during this period. C1 NIH,VETERINARIAN RESOURCES PROGRAM,BLDG 10,ROOM 10 N262,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 27 TC 5 Z9 5 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0001-5598 J9 ACTA ENDOCRINOL-COP JI Acta Endocrinol. PD OCT PY 1993 VL 129 IS 4 BP 371 EP 374 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ME956 UT WOS:A1993ME95600018 PM 8237258 ER PT J AU DHANIREDDY, R SENGER, D MUKHERJEE, BB MUKHERJEE, AB AF DHANIREDDY, R SENGER, D MUKHERJEE, BB MUKHERJEE, AB TI OSTEOPONTIN IN HUMAN-MILK FROM MOTHERS OF PREMATURE-INFANTS SO ACTA PAEDIATRICA LA English DT Note ID RAT BONE; PROTEINS C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MCGILL UNIV,DEPT BIOL,MONTREAL H3A 2T5,QUEBEC,CANADA. NICHHD,HUMAN GENET BRANCH,DEV GENET SECT,BETHESDA,MD 20892. RP DHANIREDDY, R (reprint author), GEORGETOWN UNIV,MED CTR,DEPT PEDIAT,WASHINGTON,DC 20007, USA. RI Dhanireddy, Ramasubbareddy/I-3699-2016 OI Dhanireddy, Ramasubbareddy/0000-0002-8787-6499 NR 12 TC 4 Z9 4 U1 0 U2 2 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD OCT PY 1993 VL 82 IS 10 BP 821 EP 822 PG 2 WC Pediatrics SC Pediatrics GA MA602 UT WOS:A1993MA60200005 PM 8241638 ER PT J AU TOKUNAGA, M UEMURA, Y TOKUDOME, T ISHIDATE, T MASUDA, H OKAZAKI, E KANEKO, K NAOE, S ITO, M OKAMURA, A SHIMADA, A SATO, E LAND, CE AF TOKUNAGA, M UEMURA, Y TOKUDOME, T ISHIDATE, T MASUDA, H OKAZAKI, E KANEKO, K NAOE, S ITO, M OKAMURA, A SHIMADA, A SATO, E LAND, CE TI EPSTEIN-BARR-VIRUS RELATED GASTRIC-CANCER IN JAPAN - A MOLECULAR PATHO-EPIDEMIOLOGIC STUDY SO ACTA PATHOLOGICA JAPONICA LA English DT Article DE EPSTEIN-BARR VIRUS; GASTRIC CARCINOMA; IN-SITU HYBRIDIZATION ID LYMPHOEPITHELIOMA-LIKE CARCINOMA; LYMPHOID STROMA; DNA AB Epstein-Barr virus (EBV) involvement in gastric carcinoma has been demonstrated by the presence of EBV genomes and EBV-encoded small RNA (EBER) in the carcinoma cells, monoclonal proliferation of EBV-infected carcinoma cells and elevated antibody titers. The present study was conducted to investigate the prevalence of EBV involvement among gastric carcinomas observed in nine Japanese cities with varying gastric cancer rates. In situ hybridization of EBER-1 was applied to paraffin sections from 1848 carcinomas observed in 1795 cases and EBV involvement was detected based on uniform hybridization in carcinoma cells. Epstein-Barr virus was detected in 6.6% of lesions and 6.7% of cases. The rate of EBV involvement did not vary significantly for each city and there was no correlation with underlying gastric cancer mortality rates. Thus, geographic variation of gastric cancer rates within Japan cannot be explained in terms of EBV involvement. Epstein-Barr virus-related gastric carcinoma is one of the most common EBV-related tumors in Japan. The involvement of EBV was significantly more frequent among males than among females, mainly for cancers occurring in the upper and middle part of the stomach, and exhibited more variation by cell type among males. These observations suggest that other factors yet to be discovered may modulate the causal role of EBV in gastric carcinogenesis. C1 HAKODATE MUNICIPAL HOSP,DEPT PATHOL,HAKODATE,JAPAN. AKITA UNIV,SCH MED,DEPT PATHOL 2,AKITA 010,JAPAN. NIIGATA CITY HOSP,DEPT CLIN PATHOL,NIIGATA,JAPAN. OMIYA RED CROSS HOSP,DEPT PATHOL,YONO,JAPAN. TOHO UNIV,OHASHI HOSP,SCH MED,DEPT PATHOL,TOKYO 143,JAPAN. NAGOYA UNIV,SCH MED,DEPT PATHOL 1,NAGOYA,AICHI 466,JAPAN. KANSAI MED UNIV HOSP,DEPT PATHOL,MORIGUCHI,JAPAN. OKINAWA RED CROSS HOSP,DEPT LAB,NAHA,JAPAN. KAGOSHIMA UNIV,SCH MED,DEPT PATHOL 2,KAGOSHIMA 890,JAPAN. NCI,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP TOKUNAGA, M (reprint author), KAGOSHIMA CITY HOSP,DEPT PATHOL,20-17 KAJIYA CHO,KAGOSHIMA 892,JAPAN. NR 24 TC 110 Z9 118 U1 0 U2 2 PU BLACKWELL SCIENCE PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON VICTORIA 3053, AUSTRALIA SN 0001-6632 J9 ACTA PATHOL JAPON PD OCT PY 1993 VL 43 IS 10 BP 574 EP 581 PG 8 WC Pathology SC Pathology GA MC043 UT WOS:A1993MC04300005 PM 8291445 ER PT J AU WEIFFENBACH, JM AF WEIFFENBACH, JM TI TOUCH AND TASTE IN THE MOUTH - PRESENCE AND CHARACTER OF SAPID SOLUTIONS SO ACTA PSYCHOLOGICA LA English DT Article AB Complex dynamic properties of a bolus in the mouth are specified by touch. Cooperation between touch and taste may help to specify the character of the bolus. The role of touch in specifying the presence of the oral bolus, in contrast to it's characteristics, remains a theoretical and experimental challenge. RP WEIFFENBACH, JM (reprint author), NIH,BLDG 10,ROOM 1-N-114,BETHESDA,MD 20892, USA. NR 9 TC 5 Z9 5 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0001-6918 J9 ACTA PSYCHOL JI Acta Psychol. PD OCT PY 1993 VL 84 IS 1 BP 127 EP 130 DI 10.1016/0001-6918(93)90079-7 PG 4 WC Psychology, Experimental SC Psychology GA MA968 UT WOS:A1993MA96800012 PM 8237453 ER PT J AU KOCHMAN, K KOWATCH, MA ROTH, GS BLACKMAN, MR AF KOCHMAN, K KOWATCH, MA ROTH, GS BLACKMAN, MR TI EFFECTS OF AGE AND SEX ON BASAL AND DOPAMINE-INHIBITED IN-VITRO PROLACTIN-RELEASE, AND DOPAMINE-RECEPTOR BINDING, BY THE RAT ADENOHYPOPHYSIS SO AGING-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE DOPAMINE; PROLACTIN; RAT ADENOHYPOPHYSIS AB We measured basal and dopamine-inhibited pituitary cell prolactin (PRL) release in vitro, and dopamine receptor binding in pituitary homogenates, from intact male and female Wistar rats of varying ages. During 48-72 hours in culture, the base-line secretion rate of PRL from pituitary cells of old (24 months) male rats was less than one-half that from cells of mature (6 months) male rats, whereas the corresponding basal secretion rate of PRL from cells of old female rats was nearly 3-fold greater than that from cells of mature female rats (p<0.001). After in vitro exposure to various concentrations of dopamine (10(-10)M to 10(-6)M), PRL secretion decreased from pituitary cells of both mature and old rats (p<0.001). However, repeated measures analysis of variance revealed an age-related, dose-dependent decrease in the magnitude of dopamine-inhibited PRL release from cells of both male and female rats (p<0.001). Dopamine receptor number did not differ with age (3-25 months), but was 2 to 3-fold greater in female than in male rats (p<0.01). Receptor affinity was decreased with age only in female rats, and was greater in female than in male rats (p<0.05). These data suggest that the decrease in dopamine-inhibited PRL release from pituitary cells of old male and female rats is not due to altered Pituitary dopamine receptor binding, despite certain sex differences. C1 NIA,GERONTOL RES CTR,MOLEC PHYSIOL & GENET SECT CELLULAR & MOLEC BIOL LAB,BALTIMORE,MD 21224. NR 0 TC 2 Z9 2 U1 0 U2 0 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 1993 VL 5 IS 5 BP 349 EP 356 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA MF345 UT WOS:A1993MF34500003 PM 8123695 ER PT J AU EDDLESTON, M DELATORRE, JC XU, JY DORFMAN, N NOTKINS, A ZOLLAPAZNER, S OLDSTONE, MBA AF EDDLESTON, M DELATORRE, JC XU, JY DORFMAN, N NOTKINS, A ZOLLAPAZNER, S OLDSTONE, MBA TI MOLECULAR MIMICRY ACCOMPANYING HIV-1 INFECTION - HUMAN MONOCLONAL-ANTIBODIES THAT BIND TO GP41 AND TO ASTROCYTES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS DEMENTIA COMPLEX; NERVOUS-SYSTEM; AUTOIMMUNE-DISEASE; ZIDOVUDINE; PROTEIN; COHORT; BRAIN; AZT; ABNORMALITIES AB Monoclonal antibodies that bound to HIV gp41 and cross-reacted with astrocytes were recovered from the blood of three patients infected with HIV-1. Mapping of the specificity of these monoclonal antibodies, using synthetic gp41 peptides, located their epitope to amino acids 644-663 and established their conformation dependence. Six other human monoclonal anti-HIV antibodies were found to bind to HIV gp41 or gp120 but not to reactive astrocytes in brain tissue. Sharing of linear or conformational protein determinants between disparate viral and host proteins is termed molecular mimicry. The consequences of such mimicry by anti-viral antibodies interacting with astrocytes may play a role in the dementia of AIDS patients since a major function of astrocytes is to maintain the appropriate milieu for neuronal function. The finding of such cross-reactive antibodies adds to the evidence for a possible autoimmune pathogenesis in some of the disease manifestations accompanying HIV infection. C1 Scripps Res Inst, DEPT NEUROPHARMACOL, DIV VIROL, 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USA. NYU, SCH MED, DEPT PATHOL, NEW YORK, NY 10003 USA. NIDR, ORAL MED LAB, BETHESDA, MD 20892 USA. FU NIAID NIH HHS [AI 32424]; NIMH NIH HHS [MHA47680] NR 43 TC 19 Z9 19 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 1993 VL 9 IS 10 BP 939 EP 944 DI 10.1089/aid.1993.9.939 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA MF842 UT WOS:A1993MF84200002 PM 7506553 ER PT J AU ORAVECZ, T NORCROSS, MA AF ORAVECZ, T NORCROSS, MA TI COSTIMULATORY PROPERTIES OF THE HUMAN CD4 MOLECULE - ENHANCEMENT OF CD3-INDUCED T-CELL ACTIVATION BY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 THROUGH VIRAL ENVELOPE GLYCOPROTEIN GP120 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID LYMPHOCYTES-T; HIV-INFECTION; MONOCLONAL-ANTIBODIES; SIGNAL TRANSDUCTION; KINASE P56LCK; CROSS-LINKING; HTLV-III; RECEPTOR; ANTIGEN; RESPONSES AB This study was designed to investigate the T cell-costimulatory activity of ligands binding to different regions on the human CD4 molecule. We assayed the costimulatory properties of a panel of CD4 MAbs, intact HIV, and viral envelope glycoproteins in CD3-induced activation of resting T cell subpopulations. Our data using MAbs reveal epitope-specific variations in the functional activities of CD4 MAbs under specific conditions in which CD3 and CD4 molecules are co-cross-linked. We show that both naive and memory CD4+ T cell subsets are susceptible to CD4-mediated costimulation, which overcomes the functional differences between the two cell populations in responsiveness to CD3 MAbs. We show for the first time that, analogous to CD4 MAbs, preparations of HIV and viral envelope glycoprotein gp120 are also potent costimulators of T cell proliferation and IL-2 production. On the basis of these results we propose possible mechanisms for polyclonal cell activation in the course of HIV infection and suggest that viral inhibitory and costimulatory effects may together disrupt the normal balanced function of the immune system, leading to AIDS. C1 NIH,US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BLDG 29A,ROOM 3B10,BETHESDA,MD 20892. NR 50 TC 16 Z9 16 U1 1 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 1993 VL 9 IS 10 BP 945 EP 955 DI 10.1089/aid.1993.9.945 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA MF842 UT WOS:A1993MF84200003 PM 7506554 ER PT J AU SETH, A HODGE, DR THOMPSON, DM ROBINSON, L PANAYIOTAKIS, A WATSON, DK PAPAS, TS AF SETH, A HODGE, DR THOMPSON, DM ROBINSON, L PANAYIOTAKIS, A WATSON, DK PAPAS, TS TI ETS FAMILY PROTEINS ACTIVATE TRANSCRIPTION FROM HIV-1 LONG TERMINAL REPEAT SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NECROSIS FACTOR-ALPHA; NF-KAPPA-B; DNA-BINDING; GENE-EXPRESSION; NUCLEOTIDE-SEQUENCE; ENHANCER ELEMENT; CORE SEQUENCE; T-CELLS; C-FOS AB ets is a multigene family and its members share a common ETS DNA-binding domain. ETS proteins activate transcription via binding to a purine-rich GGAA core sequence located in promoters/enhancers of various genes, including several that are transcriptionally active in T cells. The ETS1, ETS2, and ERBG/Hu-FLI-1 gene expression pattern also suggests a role for these genes in cells of hematopoietic lineage. The HIV-1 LTR core enhancer contains two 10-base pair direct repeat sequences (left and right) that are required for regulation of HIV-1 mRNA expression by host transcription factors, including NFkappaB. Two ETS-binding sites are present in the core enhancer of all the HIV-1 isolates reported so far. In our studies, we utilized HIV-1 HXB2 and HIV-1 Z2Z6 core enhancers because the Z2Z6 strain has a single point mutation flanking the right ETS-binding site. We demonstrate that the ETS1, ETS2, and ERGB/Hu-FLI-1 proteins can trans-activate transcription from both the HXB2 and Z2Z6 core enhancer when linked to a reporter (cat) gene. In addition, we show that the DNA binding and trans-activation with the Z2Z6 core enhancer is at least 40-fold higher than that observed with the HXB2 core enhancer. Further, we provide evidence that the marked increase in binding and trans-activation with Z2Z6 core enhancer sequences is due to the substitution of a flanking T residue in HXB2 TGGAA) by a C residue in Z2Z6 (CGGAA) isolate, thus generating an optimal ETS-binding core (CGGAA) sequence. C1 PROGRAM RESOURCES INC,DYNCORP,FREDERICK,MD 21702. RP SETH, A (reprint author), NCI,MOLEC ONCOL LAB,POB B,BLDG 469,RM 211,FREDERICK,MD 21702, USA. NR 46 TC 38 Z9 38 U1 0 U2 3 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 1993 VL 9 IS 10 BP 1017 EP 1023 DI 10.1089/aid.1993.9.1017 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA MF842 UT WOS:A1993MF84200011 PM 8280476 ER PT J AU MICHAELS, FH HATTORI, N GALLO, RC FRANCHINI, G AF MICHAELS, FH HATTORI, N GALLO, RC FRANCHINI, G TI THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) VIF PROTEIN IS LOCATED IN THE CYTOPLASM OF INFECTED-CELLS AND ITS EFFECT ON VIRAL REPLICATION IS EQUIVALENT IN HIV-2 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID SOR GENE-PRODUCT; MESSENGER-RNA; HTLV-III/LAV; HUMAN-SERA; T-CELLS; RETROVIRUS; ANTIBODIES; AIDS; TRANSMISSION; LYMPHOCYTES AB The human immunodeficiency virus type 1 (HIV-1) vif gene (viral infectivity gene) plays an important role in viral replication in vitro. We demonstrated that the Vif protein is membrane associated in HIV-1-infected cells and have investigated the role in viral replication of the equivalent gene in HIV-2. We constructed an HIV-2 vif minus mutant and studied its virulence and cellular tropism in vitro. Parallel experiments were also performed with an HIV-1 vif mutant to ascertain whether the two distantly related HIV-2 and HIV-1 genes might exert the same effect on viral replication. The results indicated that both HIV-1 and HIV-2 vif minus cell-free infection was not impaired when the SupT-1 cell line was used. However, differential degrees of impairment in viral replication were observed when other cell lines were used (Molt-3, U-937). Nevertheless, when viral production could not be detected, rescue experiments by coculture with the permissive cell line SupT-1 were generally positive, indicating that the viruses were still present in the inoculated cells. In contrast, when primary human cells (peripheral blood mononuclear cells and purified macrophages) were infected with HIV-1 and HIV-2 vif minus viruses no productive infection was observed and generally no virus was rescued by cocultivation. Thus, like in HIV-1, the vif gene of HIV-2 is crucial for viral infectivity in primary cells and might represent an attractive target for therapy. C1 NCI,TUMOR CELL BIOL LAB,BLDG 37,RM 6A01,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 31 TC 42 Z9 44 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 1993 VL 9 IS 10 BP 1025 EP 1030 DI 10.1089/aid.1993.9.1025 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA MF842 UT WOS:A1993MF84200012 PM 8280477 ER PT J AU ABOULAFIA, DM FEIGAL, E VRANZIAN, K BENNETT, C BLATTNER, W MOSS, A SLAMON, D AF ABOULAFIA, DM FEIGAL, E VRANZIAN, K BENNETT, C BLATTNER, W MOSS, A SLAMON, D TI HUMAN T-CELL LEUKEMIA-VIRUS (HTLV-I/II) SERODIAGNOSTIC TESTING - DISPARATE RESULTS AMONG A COHORT OF INTRAVENOUS-DRUG-USERS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID II INFECTION; ANTIBODIES; BLOOD; TRANSMISSION; ANTIGEN; ABUSERS; DONORS; SERA; ATL; MEN AB Three hundred and forty-six sera collected over-a 2-year period from 154 San Francisco IV drug users were subjected to HTLV-I/II RIPA, Western blot (WB), Du Pont ELISA, and p24 radioimmunoassay (RIA). Tests were performed at separate sites and code not broken until study end. RIPA-positive and -negative controls consisted of Japanese adult T cell leukemia patients, healthy blood donors, and non-IV drug-using HIV-positive men. RIPA identified HTLV-I/II-positive sera not identified by the other tests. Positive RIPAs were noted in 43% of negative ELISAs (n = 279), 34% of negative WBs (n = 243), and 40% of negative RIAs (n = 270). Seventy-two sera were negative by all 3 assays, but were RIPA positive. All sera positive by RIA (n = 76) and WB (n = 67), and 66 of 67 by ELISA, were positive by RIPA. Thirty-five of 36 indeterminate WBs were RIPA positive. Seven samples indeterminate by RIPA were negative by WB and RIA; one of seven was positive by ELISA. In all instances, samples negative by RIPA (n = 154) were ELISA, p24 RIA, and WB negative or indeterminate. We conclude that when studying HTLV-I/II-endemic cohorts, screening ELISA or RIA followed by confirmatory WB or RIPA only of seropositive samples may result in a substantial number of undetected cases. Additional studies focusing on performance characteristics of serodiagnostic tests are needed to ensure accurate inferences are made in assessing HTLV-I/II prevalence rates among high-risk groups. The RIPA may be a uniquely sensitive assay to detect HTLV-I/II gene-encoded products. C1 UNIV WASHINGTON,SEATTLE,WA 98195. NCI,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94110. DUKE UNIV,DEPT HEMATOL ONCOL,DURHAM,NC 27705. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. RP ABOULAFIA, DM (reprint author), VIRGINIA MASON MED CTR,DIV HEMATOL & ONCOL,1100 9TH AVE,POB 900,SEATTLE,WA 98111, USA. NR 42 TC 10 Z9 10 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 1993 VL 9 IS 10 BP 1043 EP 1050 DI 10.1089/aid.1993.9.1043 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA MF842 UT WOS:A1993MF84200015 PM 7904169 ER PT J AU ARTHUR, LO BESS, JW SOWDER, RC BENVENISTE, RE HENDERSON, LE AF ARTHUR, LO BESS, JW SOWDER, RC BENVENISTE, RE HENDERSON, LE TI CELLULAR PROTEINS ARE PHYSICALLY ASSOCIATED WITH IMMUNODEFICIENCY VIRUSES AND ANTISERA TO THESE PROTEINS NEUTRALIZE VIRUS-INFECTION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,FCRDC,PRI DYNCORP,AIDS VACCINE PROGRAM,FREDERICK,MD 21702. RI Bess, Jr., Julian/B-5343-2012 NR 0 TC 0 Z9 0 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 1993 VL 9 SU 1 BP S83 EP S83 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ME188 UT WOS:A1993ME18800053 ER PT J AU BELSHE, RB CLEMENTS, ML DOLIN, R COREY, L GRAHAM, B BOLOGNESI, D STABLEIN, D EIBL, K FAST, P AF BELSHE, RB CLEMENTS, ML DOLIN, R COREY, L GRAHAM, B BOLOGNESI, D STABLEIN, D EIBL, K FAST, P TI SAFETY AND IMMUNOGENICITY OF FULLY GLYCOSYLATED RGP160 III, VACCINE IN LOW-RISK VOLUNTEERS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIAID,AIDS VACCINE CLIN TRIALS NETWORK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 1993 VL 9 SU 1 BP S113 EP S113 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ME188 UT WOS:A1993ME18800100 ER PT J AU CEASE, KB POTCOVA, CA GROENEVELD, LM PROBERT, WS DUNLOP, NM NARA, PL AF CEASE, KB POTCOVA, CA GROENEVELD, LM PROBERT, WS DUNLOP, NM NARA, PL TI MODULATION OF THE IMMUNE-RESPONSE TO HIV-1 ENVELOPE PROTEIN USING A MIXED IMMUNOGEN STRATEGY SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 UNIV MICHIGAN,MED CTR,ANN ARBOR,MI 48109. NCI,FCRDC,VIRUS BIOL SECT,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 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 1993 VL 9 SU 1 BP S29 EP S29 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ME188 UT WOS:A1993ME18800009 ER PT J AU DULIEGE, AM FELTON, S GOEDERT, JJ AF DULIEGE, AM FELTON, S GOEDERT, JJ TI HIGH-RISK OF HIV-1 INFECTION FOR 1ST-BORN TWIN - THE ROLE OF INTRA-PARTUM TRANSMISSION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 GENENTECH INC,INT REGISTRY HIV EXPOSED TWINS,S SAN FRANCISCO,CA 94080. RTI,WASHINGTON,DC. NCI,VIRAL EPIDEMIOL SECT,ROCKVILLE,MD. NR 0 TC 0 Z9 0 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 1993 VL 9 SU 1 BP S84 EP S84 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ME188 UT WOS:A1993ME18800055 ER PT J AU EDDY, GA LEWIS, MG MCCUTCHAN, FE BENVENISTE, RE JAHRLING, PB LAI, CY BURKE, DS SHAFFERMAN, A AF EDDY, GA LEWIS, MG MCCUTCHAN, FE BENVENISTE, RE JAHRLING, PB LAI, CY BURKE, DS SHAFFERMAN, A TI ACTIVE AND PASSIVE-IMMUNIZATION INDUCED BY ENVELOPE PEPTIDES PROTECTS RHESUS MACAQUES FROM SIV AIDS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 ISRAEL INST BIOL RES,IL-70450 NESS ZIONA,ISRAEL. WALTER REED ARMY INST RES,WASHINGTON,DC 20307. HENRY M JACKSON FDN,ROCKVILLE,MD. USAMRIID,FREDERICK,MD. NCI,VIRAL CARCINOGEN LAB,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 U1 0 U2 2 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 1993 VL 9 SU 1 BP S109 EP S109 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ME188 UT WOS:A1993ME18800094 ER PT J AU GOLDENTHAL, KL CAVAGNARO, JA ALVING, CR VOGEL, FR AF GOLDENTHAL, KL CAVAGNARO, JA ALVING, CR VOGEL, FR TI SAFETY EVALUATION OF VACCINE ADJUVANTS - NATIONAL-COOPERATIVE-VACCINE-DEVELOPMENT-MEETING-WORKING-GROUP SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNOLOGICAL ADJUVANTS; CLINICAL-TRIAL; VIRUS VACCINE; INFLUENZA; IMMUNOTHERAPY; INTERFERON C1 NIAID, DIV AIDS,VACCINE RES & DEV BRANCH,SOLAR BLDG, ROOM 2B06, BETHESDA, MD 20892 USA. US FDA, CTR BIOL EVALUAT & RES, BETHESDA, MD 20892 USA. WALTER REED ARMY INST RES, DEPT MEMBRANE BIOCHEM, WASHINGTON, DC 20307 USA. NR 35 TC 24 Z9 27 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 1993 VL 9 SU 1 BP S47 EP S51 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ME188 UT WOS:A1993ME18800034 ER PT J AU GRADON, JD SCHOOLEY, RT SCHNITTMAN, SM AF GRADON, JD SCHOOLEY, RT SCHNITTMAN, SM TI REPORT ON THE THERAPEUTIC VACCINE WORKSHOP - NATIONAL-COOPERATIVE-VACCINE-DEVELOPMENT-GROUP MEETING SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article C1 NIAID,DAIDS,MED BRANCH,ROOM 2C22,SOLAR BLDG,6003 EXECUT BLVD,BETHESDA,MD 20892. UNIV COLORADO,HLTH SCI CTR,DIV INFECT DIS,DENVER,CO 80262. NR 0 TC 1 Z9 1 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 1993 VL 9 SU 1 BP S55 EP S58 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ME188 UT WOS:A1993ME18800036 ER PT J AU HOFF, R OSHAUGHNESSY, MV SCHOCHETMAN, G WEBER, DJ MCAULEY, M LAWRENCE, DN AF HOFF, R OSHAUGHNESSY, MV SCHOCHETMAN, G WEBER, DJ MCAULEY, M LAWRENCE, DN TI MONITORING IMMUNOGENICITY AND INFECTION IN HIV VACCINE EFFICACY TRIALS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID DIAGNOSIS C1 CTR DIS CONTROL,DIV HIV AIDS,ATLANTA,GA 30333. ST PAULS HOSP,BRITISH COLUMBIA CTR EXCELLENCE HIV AIDS,VANCOUVER V67 IY6,BC,CANADA. RP HOFF, R (reprint author), NIA,DIV AIDS,VACCINE TRIALS & EPIDEMIOL BRANCH,VACCINE TRIALS SECT,BETHESDA,MD 20892, USA. NR 6 TC 6 Z9 6 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 1993 VL 9 SU 1 BP S71 EP S74 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ME188 UT WOS:A1993ME18800039 ER PT J AU JOHNSTON, M FAST, P SCHULTZ, A HOTH, D AF JOHNSTON, M FAST, P SCHULTZ, A HOTH, D TI PROGRESS TOWARD DEVELOPMENT OF A VACCINE TO PREVENT AIDS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; LYMPHOCYTE PROLIFERATIVE RESPONSES; RECOMBINANT GP160; IMMUNODOMINANT EPITOPE; ENVELOPE GLYCOPROTEIN; CANDIDATE VACCINE; HIV-1; INFECTION; SAFETY; IMMUNOGENICITY AB Since the first reports that a whole-killed SIV vaccine protected monkeys from SIV infection, research on the design and development of candidate prophylactic vaccines to prevent the acquired immunodeficiency syndrome (AIDS) has escalated rapidly. Over 20 candidates have undergone preclinical evaluation for safety and immunogenicity. A few have demonstrated the ability to protect animals from intravenous and/or mucosal challenge with homologous HIV or SIV given shortly after immunization was completed. Several vaccine candidates have entered phase 1 clinical testing in uninfected volunteers and two candidates entered phase 2 testing in larger numbers of individuals, including those at higher risk for HIV infection. In addition, the complex process of preparing for phase 3 trials has begun in the United States and other countries. The purpose of this review is to summarize the status of HIV vaccine development and to highlight critical questions that need to be addressed. Current challenges include increasing the magnitude, duration, and breadth of the immune response to candidate vaccines in humans, consistently eliciting CD8+ cytotoxic T cells in humans, and using animal models and/or in vitro approaches to determine if the immune responses to candidate vaccines in human volunteers might be protective against HIV strains that individuals at risk are likely to encounter. RP JOHNSTON, M (reprint author), NIAID,DIV AIDS,SOLAR BLDG,ROOM 2C07,6003 EXECUTIVE BLVD,BETHESDA,MD 20892, USA. NR 73 TC 2 Z9 2 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 1993 VL 9 SU 1 BP S117 EP S122 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ME188 UT WOS:A1993ME18800105 ER PT J AU KANG, CY KANDASAMY, H NARA, P AF KANG, CY KANDASAMY, H NARA, P TI IDENTIFICATION OF A NEW NEUTRALIZING EPITOPE CONFORMATIONALLY AFFECTED BY THE ATTACHMENT OF CD4 TO GP120 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 IDEC PHARMACEUT CORP,LA JOLLA,CA. NCI,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 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 1993 VL 9 SU 1 BP S76 EP S76 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ME188 UT WOS:A1993ME18800041 ER PT J AU KEEFER, M BELSHE, R CLEMENTS, M GRAHAM, B COREY, L BOLOGNESI, D STABLEIN, D FAST, P MONTEFIORI, D SMITH, G DOLIN, R AF KEEFER, M BELSHE, R CLEMENTS, M GRAHAM, B COREY, L BOLOGNESI, D STABLEIN, D FAST, P MONTEFIORI, D SMITH, G DOLIN, R TI SAFETY AND IMMUNOGENICITY OF LAMBDA-BACULOVIRUS DERIVED HIV-1 IIIB RECOMBINANT GP160 VACCINE (VAXSYN(R)) IN HUMANS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIAID,AIDS VACCINE CLIN TRAINS NETWORK,BETHESDA,MD 20892. MICROGENESYS INC,MERIDEN,CT. NR 0 TC 0 Z9 0 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 1993 VL 9 SU 1 BP S113 EP S113 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ME188 UT WOS:A1993ME18800101 ER PT J AU LAMBERT, JJ MCNAMARA, JG RODRIGUEZ, EM FAST, PE AF LAMBERT, JJ MCNAMARA, JG RODRIGUEZ, EM FAST, PE TI SUMMARY OF THE PERINATAL-INTERVENTION-WORKING-GROUP SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Editorial Material C1 NIAID,DIV AIDS,VACCINE RES & DEV BRANCH,2B06 SOLAR BLDG,6003 EXECUT BLDG,BETHESDA,MD 20892. UNIV ROCHESTER,DEPT PEDIAT,ROCHESTER,NY 14642. UNIV ROCHESTER,DEPT INTERNAL MED,ROCHESTER,NY 14642. NR 0 TC 3 Z9 3 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 1993 VL 9 SU 1 BP S53 EP S54 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ME188 UT WOS:A1993ME18800035 ER PT J AU LAWRENCE, DN ESPARZA, J ZOON, KC AF LAWRENCE, DN ESPARZA, J ZOON, KC TI CONSIDERATIONS ON CRITERIA FOR COMMENCEMENT OF HIV VACCINE EFFICACY TRIALS - A WORKING GROUP SUMMARY SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article C1 WHO,VACCINE DEV UNIT,GLOBAL PROGRAMME AIDS,CH-1211 GENEVA 27,SWITZERLAND. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. RP LAWRENCE, DN (reprint author), NIAID,DIV AIDS,ROOM 2B09,SOLAR BLDG,6003 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 0 TC 8 Z9 8 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 1993 VL 9 SU 1 BP S65 EP S69 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ME188 UT WOS:A1993ME18800038 ER PT J AU RAPHAEL, D COREY, L GRAHAM, B WRIGHT, P MCELRATH, J KEEFER, M MATTHEWS, T STABLEIN, D DEKKER, C AF RAPHAEL, D COREY, L GRAHAM, B WRIGHT, P MCELRATH, J KEEFER, M MATTHEWS, T STABLEIN, D DEKKER, C TI SAFETY AND IMMUNOGENICITY OF AN HIV VACCINE CANDIDATE, ENV 2-3, IN COMBINATION WITH MTP-PE/MF59 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIAID,BETHESDA,MD 20892. CHIRON CORP,EMERYVILLE,CA. NR 0 TC 0 Z9 0 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 1993 VL 9 SU 1 BP S111 EP S111 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ME188 UT WOS:A1993ME18800097 ER PT J AU RIDA, W MEIER, P STEVENS, C AF RIDA, W MEIER, P STEVENS, C TI DESIGN AND IMPLEMENTATION OF HIV VACCINE EFFICACY TRIALS - A WORKING GROUP SUMMARY SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article C1 NEW YORK BLOOD CTR,NEW YORK,NY 10021. UNIV CHICAGO,DEPT STAT,CHICAGO,IL 60637. RP RIDA, W (reprint author), NIAID,DIV ADS,BIOSTAT RES BRANCH,ROOM 2B25,SOLAR BLDG,BETHESDA,MD 20892, USA. NR 3 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 1993 VL 9 SU 1 BP S59 EP S63 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ME188 UT WOS:A1993ME18800037 ER PT J AU SCHWARTZ, D CLEMENTS, ML HOPKINS, J BERMAN, P DULIEGE, AM TWADELL, T AMMANN, A BELSHE, R GORSE, G MATTHEWS, T BOLOGNESI, D FAST, P SPOSTO, R STABLEIN, D AF SCHWARTZ, D CLEMENTS, ML HOPKINS, J BERMAN, P DULIEGE, AM TWADELL, T AMMANN, A BELSHE, R GORSE, G MATTHEWS, T BOLOGNESI, D FAST, P SPOSTO, R STABLEIN, D TI SAFETY AND IMMUNOGENICITY OF GENENTECH-IIIB RGP 120/HIV-1 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 GENENTECH INC,S SAN FRANCISCO,CA 94080. NIAID,AVEG,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 1993 VL 9 SU 1 BP S112 EP S112 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ME188 UT WOS:A1993ME18800099 ER PT J AU UGEN, KE GOEDERT, JJ BOYER, J REFAELI, Y FRANK, I WILLOUGHBY, A LANDESMAN, S RUBINSTEIN, A EMMONS, TK WILLIAMS, WV WEINER, DB AF UGEN, KE GOEDERT, JJ BOYER, J REFAELI, Y FRANK, I WILLOUGHBY, A LANDESMAN, S RUBINSTEIN, A EMMONS, TK WILLIAMS, WV WEINER, DB TI VERTICAL TRANSMISSION OF HIV-1 INFECTION - REACTIVITY OF MATERNAL SERA TO HIV-1 GP120 AND GP41 PEPTIDES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. UNIV PENN,PHILADELPHIA,PA 19104. NCI,VIRAL EPIDEMIOL LAB,FREDERICK,MD 21701. NICHHD,ROCKVILLE,MD 20852. SUNY HLTH SCI CTR BROOKLYN,BROOKLYN,NY 11203. YESHIVA UNIV ALBERT EINSTEIN COLL MED,BRONX,NY 10461. RI Weiner, David/H-8579-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 1993 VL 9 SU 1 BP S76 EP S76 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ME188 UT WOS:A1993ME18800042 ER PT J AU VERMUND, SH FISCHER, RD HOFF, R RIDA, WN SHEON, AR LAWRENCE, DN HOTH, DF BARKER, LF AF VERMUND, SH FISCHER, RD HOFF, R RIDA, WN SHEON, AR LAWRENCE, DN HOTH, DF BARKER, LF TI PREPARING FOR HIV VACCINE EFFICACY TRIALS - PARTNERSHIPS AND CHALLENGES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS AB Initiation of clinical efficacy trials of candidate human immunodeficiency virus (HIV) vaccines may be scientifically and ethically warranted in the next few years. The National Institute of Allergy and Infectious Diseases (NIAID) is making preparations to start trials with minimal delay as soon as a suitable candidate vaccine becomes available. NIAID is sponsoring the establishment of an infrastructure for epidemiological studies of populations at potential sites for such trials. In field trials, we will need to measure suitable end points-infection, immunological status, and clinical status-necessary to judge vaccine effectiveness in preventing infection and/or disease. Difficulties in recruiting and following high-risk populations present a major research challenge. The many scientific, ethical, social, legal, and political issues related to such trials are being addressed in partnership with many groups, both in the United States and abroad. This partnership must include the public and private sectors: communities experiencing epidemic HIV spread, companies developing candidate vaccines, U.S. and international agencies, universities, and governments. Effective HIV prevention will require persistent attention to behavior change, including partner reduction and condom use, even as we develop and test candidate vaccines to prevent HIV and the acquired immunodeficiency syndrome (AIDS). RP VERMUND, SH (reprint author), NIAID,DIV AIDS,CRP,VACCINES TRIALS & EPIDEMIOL BRANCH,ROOM 2A42,BETHESDA,MD 20892, USA. NR 20 TC 23 Z9 23 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 1993 VL 9 SU 1 BP S127 EP S132 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ME188 UT WOS:A1993ME18800108 ER PT J AU VOGEL, FR AF VOGEL, FR TI ADJUVANT OVERVIEW SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIAID,DIV AIDS,VACCINE RES & DEV BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 1993 VL 9 SU 1 BP S91 EP S91 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ME188 UT WOS:A1993ME18800066 ER PT J AU HUNT, WA AF HUNT, WA TI NEUROSCIENCE RESEARCH - HOW HAS IT CONTRIBUTED TO OUR UNDERSTANDING OF ALCOHOL-ABUSE AND ALCOHOLISM - A REVIEW SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE MEMBRANES; ION CHANNELS; NEUROTRANSMITTERS; 2ND MESSENGERS; BRAIN DAMAGE ID CHRONIC ETHANOL TREATMENT; LONG-TERM POTENTIATION; D-ASPARTATE RECEPTORS; SYNAPTOSOMAL CALCIUM-UPTAKE; GAMMA-AMINOBUTYRIC ACID; ADENYLATE-CYCLASE; BRAIN MEMBRANES; HETEROLOGOUS DESENSITIZATION; WITHDRAWAL SEIZURES; CHLORIDE CHANNELS AB Alcohol abuse and alcoholism are the greatest substance abuse problems in the United States today and contribute to numerous medical and social problems. To deal with many of these problems, an understanding of how alcohol acts on the brain is extremely important. Advances in neuroscience research have provided significant clues about where and how alcohol works on the brain. Alcohol clearly acts on membrane function, altering such processes as ion movements and neurotransmitter interactions with their receptors. Although these alcohol-induced alterations are presumed to relate to changes in behavior, this has not been clearly established. However, alcohol research is on the threshold of making a giant leap forward in our understanding the etiology of alcoholism. RP HUNT, WA (reprint author), NATL INST ALCOHOL ABUSE & ALCOHOLISM, NEUROSCI & BEHAV RES BRANCH, 5600 FISHERS LANE, ROOM 16C-05, ROCKVILLE, MD 20857 USA. NR 97 TC 64 Z9 64 U1 0 U2 4 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 1993 VL 17 IS 5 BP 1055 EP 1065 DI 10.1111/j.1530-0277.1993.tb05664.x PG 11 WC Substance Abuse SC Substance Abuse GA ME468 UT WOS:A1993ME46800022 PM 7506499 ER PT J AU GRANT, BF AF GRANT, BF TI ICD-10 AND PROPOSED DSM-IV HARMFUL USE OF ALCOHOL ALCOHOL-ABUSE AND DEPENDENCE, UNITED-STATES 1988 - A NOSOLOGICAL COMPARISON SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE HARMFUL USE OF ALCOHOL; ALCOHOL ABUSE; ALCOHOL DEPENDENCE; ICD-10; DSM-IV; NOSOLOGICAL COMPARISON AB The purpose of this study was to compare ICD-10 and the proposed DSM-IV (options 1 and 2) diagnostic criteria for harmful use/abuse and dependence in a representative sample of the United States general population. Harmful use/abuse and dependence categories were contrasted in terms of prevalence and overlap. The prevalences of DSM-IV diagnoses of alcohol abuse and dependence combined were much greater than those for the corresponding ICD-10 diagnoses. Disaggregation of the harmful use/abuse and dependence diagnoses showed that the major discrepancy between the classification systems resided between harmful use and abuse categories. The prevalence of the harmful use of alcohol was nearly nonexistent in this general population sample. Reasons for this and other discrepancies are discussed in terms of the hypothesized severity of the harmful use criteria, differences in the number of diagnostic criteria and the content of the ICD-10 and DSM-IV dependence categories, the relationship between the harmful use/abuse and dependence categories, and the impact of the duration criterion. RP GRANT, BF (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,ROOM 14C-26,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 11 TC 22 Z9 22 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD OCT PY 1993 VL 17 IS 5 BP 1093 EP 1101 DI 10.1111/j.1530-0277.1993.tb05670.x PG 9 WC Substance Abuse SC Substance Abuse GA ME468 UT WOS:A1993ME46800028 PM 8279672 ER PT J AU SHIRANI, J ROBERTS, WC AF SHIRANI, J ROBERTS, WC TI EPICARDIAL LIPOMA SO AMERICAN HEART JOURNAL LA English DT Note C1 NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NR 2 TC 5 Z9 5 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 1993 VL 126 IS 4 BP 1030 EP 1030 DI 10.1016/0002-8703(93)90734-Q PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA MA334 UT WOS:A1993MA33400043 PM 8213430 ER PT J AU FORMAN, MR LANZA, E YONG, LC HOLDEN, JM GRAUBARD, BI BEECHER, GR MELITZ, M BROWN, ED SMITH, JC AF FORMAN, MR LANZA, E YONG, LC HOLDEN, JM GRAUBARD, BI BEECHER, GR MELITZ, M BROWN, ED SMITH, JC TI THE CORRELATION BETWEEN 2 DIETARY ASSESSMENTS OF CAROTENOID INTAKE AND PLASMA CAROTENOID CONCENTRATIONS - APPLICATION OF A CAROTENOID FOOD-COMPOSITION DATABASE SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE CAROTENOIDS; DIET; PLASMA ID ALPHA-TOCOPHEROL LEVELS; BETA-CAROTENE; INTERINDIVIDUAL VARIATION; FREQUENCY QUESTIONNAIRE; INDIVIDUAL CAROTENOIDS; VITAMIN-E; MEN; VALIDATION; RETINOL; DESIGN AB A newly available carotenoid food-composition database providing specific carotenoid values for > 2300 foods was linked to dietary data on 57 male nonsmokers to examine the association between dietary carotenoid intake and plasma carotenoid concentrations over 3 wk when free-living. Carotenoid intake was estimated from a food-frequency questionnaire (FFQ) and 7 d of food diaries with concurrent analysis of plasma carotenoid concentrations. After adjustment for energy intake, percentage of energy from alcohol, and plasma lipid concentrations, significant diet-plasma correlations for the FFQ and the food diaries (FD) included alpha-carotene (r = 0.29 and 0.43), beta-carotene (r = 0.36 FFQ only), beta-cryptoxanthin (r = 0.46 and 0.44), lutein (r = 0.44 FD only), and lycopene (r = 0.53 FD only). Dietary carotenoid intakes were associated with plasma carotenoid concentrations for all the carotenoids except for beta-carotene when food diaries were used whereas the diet-plasma correlation for the provitamin A carotenoids were consistently significant when the FFQ was used. C1 USDA,AGR RES SERV CTR,BELTSVILLE HUMAN NUTR FACIL,BELTSVILLE,MD 20705. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. RP FORMAN, MR (reprint author), NCI,DCPC,CPRP,CANC PREVENT STUDIES BRANCH,EPN-211C,BETHESDA,MD 20892, USA. NR 27 TC 76 Z9 78 U1 0 U2 1 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 1993 VL 58 IS 4 BP 519 EP 524 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA LY888 UT WOS:A1993LY88800011 PM 8379507 ER PT J AU LEWIS, CE CAAN, B FUNKHOUSER, E HILNER, JE BRAGG, C DYER, A RACZYNSKI, JM SAVAGE, PJ ARMSTRONG, MA FRIEDMAN, GD AF LEWIS, CE CAAN, B FUNKHOUSER, E HILNER, JE BRAGG, C DYER, A RACZYNSKI, JM SAVAGE, PJ ARMSTRONG, MA FRIEDMAN, GD TI INCONSISTENT ASSOCIATIONS OF CAFFEINE-CONTAINING BEVERAGES WITH BLOOD-PRESSURE AND WITH LIPOPROTEINS - THE CARDIA STUDY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE BLOOD PRESSURE; CAFFEINE; CHOLESTEROL; COFFEE; HYPERTENSION; LIPOPROTEINS ID CORONARY HEART-DISEASE; SERUM-CHOLESTEROL LEVELS; COFFEE CONSUMPTION; CARDIOVASCULAR-DISEASE; BOILED COFFEE; YOUNG-ADULTS; FOLLOW-UP; PLASMA; MEN; DRINKING AB The authors examined associations of caffeine and caffeinated beverage intakes with blood pressure and with lipoproteins in 5,115 black and white men and women aged 18-30 years during 1985-1986. Caffeine and beverage intakes were not consistently associated with blood pressure in analyses controlling for race, sex, Keys score, sucrose intake, physical activity, oral contraceptive use, body mass index, alcohol use, age, and smoking. Associations of caffeine and beverage intakes with cholesterol, triglycerides, high-density lipoprotein cholesterol, and high-density lipoprotein2 cholesterol were also inconsistent. There is little or no association of caffeine with lipoproteins or with blood pressure in this cohort of healthy young adults. C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL 60611. KAISER PERMANENTE,DIV RES,OAKLAND,CA. UNIV ALABAMA,DIV GEN & PREVENT MED,BIRMINGHAM,AL 35294. FU NHLBI NIH HHS [N01-HC-48048, N01-HC-48047, N01-HC-48049] NR 51 TC 10 Z9 10 U1 0 U2 2 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 1993 VL 138 IS 7 BP 502 EP 507 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA MC311 UT WOS:A1993MC31100004 PM 8213754 ER PT J AU MACKE, JP HU, N HU, S BAILEY, M KING, VL BROWN, T HAMER, D NATHANS, J AF MACKE, JP HU, N HU, S BAILEY, M KING, VL BROWN, T HAMER, D NATHANS, J TI SEQUENCE VARIATION IN THE ANDROGEN RECEPTOR GENE IS NOT A COMMON DETERMINANT OF MALE SEXUAL ORIENTATION SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID BULBAR MUSCULAR-ATROPHY; SINGLE-BASE CHANGES; INSENSITIVITY SYNDROME; HOMOSEXUAL MEN; MUTATIONS; BEHAVIOR; REPEAT; BRAIN AB To test the hypothesis that DNA sequence variation in the androgen receptor gene plays a causal role in the development of male sexual orientation, we have (1) measured the degree of concordance of androgen receptor alleles in 36 pairs of homosexual brothers, (2) compared the lengths of polyglutamine and polyglycine tracts in the amino-terminal domain of the androgen receptor in a sample of 197 homosexual males and 213 unselected subjects, and (3) screened the the entire androgen receptor coding region for sequence variation by PCR and denaturing gradient-gel electrophoresis (DGGE) and/or single-strand conformation polymorphism analysis in 20 homosexual males with homosexual or bisexual brothers and one homosexual male with no homosexual brothers, and screened the amino-terminal domain of the receptor for sequence variation in an additional 44 homosexual males, 37 of whom had one or more first- or second-degree male relatives who were either homosexual or bisexual. These analyses show that (1) homosexual brothers are as likely to be discordant as concordant for androgen receptor alleles; (2) there are no large-scale differences between the distributions of polyglycine or polyglutamine tract lengths in the homosexual and control groups; and (3) coding region sequence variation is not commonly found within the androgen receptor gene of homosexual men. The DGGE screen identified two rare amino acid substitutions, ser205-to-arg and glu793-to-asp, the biological significance of which is unknown. C1 JOHNS HOPKINS UNIV,SCH MED,HOWARD HUGHES MED INST,805 PCTB,725 N WOLFE ST,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MOLEC BIOL & GENET,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT POPULAT DYNAM,BALTIMORE,MD 21218. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NORTHWESTERN UNIV,DEPT PSYCHOL,EVANSTON,IL 60201. FU NIDDK NIH HHS [DK43147] NR 32 TC 64 Z9 68 U1 0 U2 8 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 1993 VL 53 IS 4 BP 844 EP 852 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA LY627 UT WOS:A1993LY62700008 PM 8213813 ER PT J AU GOLDIN, LR WEEKS, DE AF GOLDIN, LR WEEKS, DE TI 2-LOCUS MODELS OF DISEASE - COMPARISON OF LIKELIHOOD AND NONPARAMETRIC LINKAGE METHODS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENETICALLY COMPLEX TRAITS; PEDIGREE-MEMBER METHOD; LOD SCORE; STRATEGIES; LOCUS; POWER AB The power to detect linkage for likelihood and nonparametric (Haseman-Elston, affected-sib-pair, and affected-pedigree-member) methods is compared for the case of a common, dichotomous trait resulting from the segregation of two loci. Pedigree data for several two-locus epistatic and heterogeneity models have been simulated, with one of the loci linked to a marker locus. Replicate samples of 20 three-generation pedigrees (16 individuals/pedigree) were simulated and then ascertained for having at least 6 affected individuals. The power of linkage detection calculated under the correct two-locus model is only slightly higher than that under a single locus model with reduced penetrance. As expected, the nonparametric linkage methods have somewhat lower power than does the lod-score method, the difference depending on the mode of transmission of the linked locus. Thus, for many pedigree linkage studies, the lod-score method will have the best power. However, this conclusion depends on how many times the lod score will be calculated for a given marker. The Haseman-Elston method would likely be preferable to calculating lod scores under a large number of genetic models (i.e., varying both the mode of transmission and the penetrances), since such an analysis requires an increase in the critical value of the lod criterion. The power of the affected-pedigree-member method is lower than the other methods, which can be shown to be largely due to the fact that marker genotypes for unaffected individuals are not used. C1 UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT HUMAN GENET,PITTSBURGH,PA 15260. RP GOLDIN, LR (reprint author), NIMH,CLIN NEUROGENET BRANCH,BLDG 10,ROOM 3N218,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Weeks, Daniel/B-2995-2012 FU NCRR NIH HHS [1 P41RR03655]; NHGRI NIH HHS [HG00719] NR 31 TC 61 Z9 61 U1 0 U2 0 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 1993 VL 53 IS 4 BP 908 EP 915 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA LY627 UT WOS:A1993LY62700015 PM 8213819 ER PT J AU HOROWITZ, M TZURI, G EYAL, N BEREBI, A KOLODNY, EH BRADY, RO BARTON, NW ABRAHAMOV, A ZIMRAN, A AF HOROWITZ, M TZURI, G EYAL, N BEREBI, A KOLODNY, EH BRADY, RO BARTON, NW ABRAHAMOV, A ZIMRAN, A TI PREVALENCE OF 9 MUTATIONS AMONG JEWISH AND NON-JEWISH GAUCHER DISEASE PATIENTS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID ACID BETA-GLUCOSIDASE; HUMAN GLUCOCEREBROSIDASE GENE; ACTIVATOR PROTEIN; ASSIGNMENT; IDENTIFICATION; HETEROGENEITY; CHROMOSOME-1; SEQUENCE; CLONING; ALLELES AB The frequency of nine different mutated alleles known to occur in the glucocerebrosidase gene was determined in 247 Gaucher patients, of whom 176 were of Jewish extraction, 2 were Jewish with one converted parent, and 69 were of non-jewish origin. DNA was prepared from peripheral blood, active glucocerebrosidase sequences were amplified by using the PCR technique, and the mutations were identified by using the allele-specific oligonucleotide hybridization method. The N37OS mutation appeared in 69.77% of the mutated alleles in Jewish patients and in 22.86% of the mutated alleles in non-jews. The 84GG mutation, which has not been found so far among non-jewish patients, existed in 10.17% of the disease alleles among Jewish patients. The IVS2+1. mutation constituted 2.26% of the disease alleles among Jewish patients and 1.43% among the non-Jewish patients. RecTL, a complex allele containing four. single-base-pair changes, occurred in 2.26% of the alleles in Jewish patients and was found in two (1.43%) of the patients of non-jewish extraction. Another complex allele, designated ''RecNciI'' and containing three single-point mutations, appeared in 7.8% of alleles of non-jewish patients and in only two (0.56%) of the Jewish families. The prevalence of the L444P mutation among non-jewish Gaucher patients was 31.43%, while its prevalence among Jewish patients was only 4.24%. The prevalence of two other point mutations-D409H and R463C-was 5.00% and 3.57%, respectively, among non-jewish patients and was not found among the Jewish Gaucher patient population. The prevalence of the R496H mutation, found so far only among Jewish patients, was 1.13%. The results presented demonstrate that seven mutations identify 90.40% of the mutations among Jewish patients and that these seven mutations allow diagnosis of only 73.52% of the non-jewish patients. Identification of additional mutant alleles will enhance the accuracy of carrier detection. C1 KAPLAN HOSP,DEPT HAEMATOL,IL-76100 REHOVOT,ISRAEL. NYU,SCH MED,DEPT NEUROL,NEW YORK,NY 10003. NIH,BETHESDA,MD 20892. SHAARE ZEDEK MED CTR,IL-91000 JERUSALEM,ISRAEL. RP HOROWITZ, M (reprint author), TEL AVIV UNIV,DEPT CELL RES & IMMUNOL,IL-69978 TEL AVIV,ISRAEL. NR 33 TC 81 Z9 81 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 1993 VL 53 IS 4 BP 921 EP 930 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA LY627 UT WOS:A1993LY62700017 PM 8213821 ER PT J AU GOLOMB, E FRIEDMAN, E ABASSI, ZA TRACHEWSKY, D KEISER, HR AF GOLOMB, E FRIEDMAN, E ABASSI, ZA TRACHEWSKY, D KEISER, HR TI RARE RENAL TRANSCRIPTION OF THE ATRIAL-NATRIURETIC-FACTOR GENE IN RATS - DEMONSTRATION BY POLYMERASE CHAIN-REACTION SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE ATRIAL NATRIURETIC FACTOR; POLYMERASE CHAIN REACTION; RAT AB Renal synthesis of a peptide homologous to atrial natriuretic factor (ANF) has been demonstrated. The aim of the present study was to determine if transcription of the ANF gene occurs in the kidney. Rat renal RNA was extracted from whole kidneys, and, separately, from the cortex and outer and inner medulla of rat kidneys. Probing with rat ANF-cDNA did not reveal a detectable message in Northern blot analysis, even when large quantities of RNA were used at low stringency hybridization conditions. Therefore, reverse transcription (RT) followed by 35 cycles of polymerase chain reaction (PCR) was used to search for the renal message for ANF. Two 21-mer primers encompassing the 450 base pairs (bp) of the coding region of the gene were used. Each cycle consisted of annealing at 56-degrees-C, extension at 72-degrees-C, and denaturation at 94-degrees-C. The PCR product was proven to be identical to the ANF gene by high stringency hybridization, which revealed the expected 450-bp hybrid band. Furthermore, the sequence of this product was identical to that of the coding region of the ANF gene. We used an RNA-specific PCR to obtain this band as a single reaction product. We conclude that the transcript of the ANF gene exists in the kidney, at extremely low levels. The low abundance of the RNA message raises major concerns about its physiologic relevance. Direct evidence for the translation of this transcript, and its quantification and localization, is still required to determine its significance. RP GOLOMB, E (reprint author), NHLBI,HYPERTENS ENDOCRINE BRANCH,BLDG 10,ROOM 8C103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD OCT PY 1993 VL 6 IS 10 BP 867 EP 872 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ME007 UT WOS:A1993ME00700009 PM 8267943 ER PT J AU HELD, PJ PORT, FK GAYLIN, DS WOLFE, RA WEBB, RL TURENNE, MN BLAGG, CR JONES, CA AGODOA, LYC AF HELD, PJ PORT, FK GAYLIN, DS WOLFE, RA WEBB, RL TURENNE, MN BLAGG, CR JONES, CA AGODOA, LYC TI EXCERPTS FROM UNITED-STATES RENAL DATA SYSTEM 1993 ANNUAL DATA REPORT SPONSORED BY CGH-MEDICAL-INC (COBE-GAMBRO-HOSPAL) SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article ID CADAVER KIDNEY-TRANSPLANTS; HUMAN ERYTHROPOIETIN; PERITONEAL-DIALYSIS; DISEASE; CYCLOSPORINE; MORTALITY; CHILDREN; SURVIVAL; PATIENT; THERAPY C1 UNIV MICHIGAN,USRDS COORDINATING CTR,ANN ARBOR,MI 48109. NIDDKD,DKUHD,BETHESDA,MD. RP HELD, PJ (reprint author), URBAN INST,RENAL RES PROGRAM,WASHINGTON,DC 20037, USA. NR 95 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD OCT PY 1993 VL 22 IS 4 SU 2 BP 1 EP 118 PG 118 WC Urology & Nephrology SC Urology & Nephrology GA MC540 UT WOS:A1993MC54000001 ER PT J AU PETERSON, A DRASS, J AF PETERSON, A DRASS, J TI HOW TO KEEP ADRENAL INSUFFICIENCY - IN CHECK SO AMERICAN JOURNAL OF NURSING LA English DT Article RP PETERSON, A (reprint author), NIH,CTR CLIN,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 0002-936X J9 AM J NURS JI Am. J. Nurs. PD OCT PY 1993 VL 93 IS 10 BP 36 EP 39 PG 4 WC Nursing SC Nursing GA LZ680 UT WOS:A1993LZ68000018 ER PT J AU ROMERO, R SIBAI, B CARITIS, S PAUL, R DEPP, R ROSEN, M KLEBANOFF, M SABO, V EVANS, J THOM, E CEFALO, R MCNELLIS, D AF ROMERO, R SIBAI, B CARITIS, S PAUL, R DEPP, R ROSEN, M KLEBANOFF, M SABO, V EVANS, J THOM, E CEFALO, R MCNELLIS, D TI ANTIBIOTIC-TREATMENT OF PRETERM LABOR WITH INTACT MEMBRANES - A MULTICENTER, RANDOMIZED, DOUBLE-BLINDED, PLACEBO-CONTROLLED TRIAL SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 13TH ANNUAL MEETING OF THE SOC-OF-PERINATAL-OBSTETRICIANS CY FEB 08-13, 1993 CL SAN FRANCISCO, CA SP SOC PERINATAL OBSTETRICIANS DE PARTURITION; PRETERM LABOR; PREMATURITY; ANTIBIOTICS; RANDOMIZED CLINICAL TRIAL; TOCOLYSIS; CHORIOAMNIONITIS ID UREAPLASMA-UREALYTICUM; ERYTHROMYCIN TREATMENT; BIRTH-WEIGHT; DELIVERY; INFECTION; THERAPY; WOMEN AB OBJECTIVE: Although an association between subclinical intrauterine infection and preterm birth is well established, there is conflicting evidence regarding the benefits of antibiotic administration to women in preterm labor with intact membranes. We attempted to determine the effect of ampicillin-amoxicillin and erythromycin treatment on prolongation of pregnancy, the rate of preterm birth, and neonatal morbidity in patients with preterm labor and intact membranes. STUDY DESIGN: A multicenter, randomized, double-blinded, placebo-controlled trial was designed and implemented by the Maternal-Fetal Medicine Units Network of the National Institute of Child Health and Human Development. Two hundred seventy-seven women with singleton pregnancies and preterm labor with intact membranes (24 to 34 weeks) were randomly allocated to receive either antibiotics or placebos. RESULTS: Of the 2373 patients screened for participation in this study in six medical centers, 277 women were enrolled (n = 133 for antibiotics group vs n = 144 for placebo group). In each study group, 60% of patients completed all the study medications. The overall prevalence of microbial invasion of the amniotic cavity was 5.8% (14/239). No significant difference between the antibiotic group and the placebo group was found in maternal outcomes, including duration of randomization-to-delivery interval, frequency of preterm delivery (<37 weeks), frequency of preterm premature rupture of membranes, clinical chorioamnionitis, endometritis, and number of subsequent admissions for preterm labor. Similarly, no significant difference in neonatal outcomes could be detected between the two groups including respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, sepsis, and admission and duration of newborn intensive special care unit hospitalization. CONCLUSION: The results of this study do not support the routine use of antibiotic administration to women in preterm labor with intact membranes. C1 YALE UNIV,NEW HAVEN,CT 06520. UNIV TENNESSEE CTR HLTH SCI,MEMPHIS,TN 38163. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. THOMAS JEFFERSON UNIV,PHILADELPHIA,PA. COLUMBIA UNIV,NEW YORK,NY 10027. NICHHD,EPIDEMIOL & BIOMETRY RES PROGRAM,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,CTR BIOSTAT,ROCKVILLE,MD. UNIV N CAROLINA,CHAPEL HILL,NC 27514. NICHHD,CTR RES MOTHERS & CHILDREN,ROCKVILLE,MD. OI caritis, steve/0000-0002-2169-0712 FU NICHD NIH HHS [HD 2141, HD 21366, HD 21434] NR 23 TC 84 Z9 85 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 1993 VL 169 IS 4 BP 764 EP 774 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA MC458 UT WOS:A1993MC45800002 PM 8238130 ER PT J AU ROMERO, R YOON, BH MAZOR, M GOMEZ, R DIAMOND, MP KENNEY, JS RAMIREZ, M FIDEL, PL SOROKIN, Y COTTON, D SEHGAL, P AF ROMERO, R YOON, BH MAZOR, M GOMEZ, R DIAMOND, MP KENNEY, JS RAMIREZ, M FIDEL, PL SOROKIN, Y COTTON, D SEHGAL, P TI THE DIAGNOSTIC AND PROGNOSTIC VALUE OF AMNIOTIC-FLUID WHITE BLOOD-CELL COUNT, GLUCOSE, INTERLEUKIN-6, AND GRAM STAIN IN PATIENTS WITH PRETERM LABOR AND INTACT MEMBRANES SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 13TH ANNUAL MEETING OF THE SOC-OF-PERINATAL-OBSTETRICIANS CY FEB 08-13, 1993 CL SAN FRANCISCO, CA SP SOC PERINATAL OBSTETRICIANS DE PRETERM LABOR; PARTURITION; AMNIOTIC FLUID; GLUCOSE; WHITE BLOOD CELL COUNT; AMNIOCENTESIS; INTERLEUKIN-6; CYTOKINES; PERINATAL MORBIDITY ID INTRAAMNIOTIC INFECTION; MICROBIAL INVASION; UREAPLASMA-UREALYTICUM; PREMATURE RUPTURE; ASSOCIATION; WOMEN; INFANTS; CAVITY AB OBJECTIVE: Our goal was to compare the value of amniotic fluid tests in the detection of microbial invasion of the amniotic cavity and in the relationship with the amniocentesis-to-delivery interval and neonatal complications in patients with preterm labor and intact membranes. STUDY DESIGN: Amniotic fluid was retrieved by transabdominal amniocentesis from 120 patients with preterm labor and intact membranes. Fluid was cultured for aerobic and anaerobic bacteria and for mycoplasmas. Amniotic fluid analysis included a Gram stain, white blood cell count, glucose and interleukin-6 determinations. Logistic regression and Cox's proportional hazards model were used for analysis. RESULTS: (1) The prevalence of positive amniotic fluid cultures was 9.2% (11/120); (2) patients with microbial invasion had a shorter amniocentesis-to-delivery interval and a higher neonatal complications rate than patients with a negative culture; (3) the most sensitive test for the detection of microbial invasion of the amniotic cavity was amniotic fluid interleukin-6 determinations (cutoff 11.3 ng/ml) (sensitivity; for interleukin-6 100%, for glucose 81.8%, for white blood cell count 63.6%, and for Gram stain 63.6%; p < 0.05 for all comparisons); (4) the most specific test was the Gram stain of amniotic fluid (specificity: for Gram stain 99.1%, for white blood cell count 94.5%, for interleukin-6 82.6%, and for glucose 81.6%; p < 0.01 for all); (5) of all amniotic fluid tests, interleukin-6 determinations were the only ones that had significant relationship with the amniocentesis-to-delivery interval and neonatal complications. CONCLUSION: Interleukin-6 concentrations in amniotic fluid are better indicators of microbial invasion of the amniotic cavity, amniocentesis-to-delivery interval, and neonatal complications than the amniotic fluid Gram stain, glucose concentration, or white blood cell count. C1 WAYNE STATE UNIV,SCH MED,DEPT OBSTET & GYNECOL,DETROIT,MI 48201. SEOUL NATL UNIV,SEOUL 151,SOUTH KOREA. BEN GURION UNIV NEGEV,SOROKA MED CTR,IL-84105 BEER SHEVA,ISRAEL. VANDERBILT UNIV,NASHVILLE,TN 37240. SYNTEX INC,INST IMMUNOL & BIOL SCI,PALO ALTO,CA 94304. NEW YORK MED COLL,DEPT MICROBIOL,VALHALLA,NY 10595. NEW YORK MED COLL,DEPT IMMUNOL,VALHALLA,NY 10595. NEW YORK MED COLL,DEPT MED,VALHALLA,NY 10595. NICHHD,PERINATOL BRANCH,BETHESDA,MD 20892. RP ROMERO, R (reprint author), WAYNE STATE UNIV,HUTZEL HOSP,DEPT OBSTET & GYNECOL,4707 ST ANTOINE BLVD,DETROIT,MI 48201, USA. RI Yoon, Bo Hyun/H-6344-2011; OI Diamond, Michael/0000-0001-6353-4489 FU NIAID NIH HHS [AI-16262] NR 26 TC 242 Z9 245 U1 0 U2 4 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 1993 VL 169 IS 4 BP 805 EP 816 PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA MC458 UT WOS:A1993MC45800008 PM 7694461 ER PT J AU MOLNAR, M ROMERO, R HERTELENDY, F AF MOLNAR, M ROMERO, R HERTELENDY, F TI INTERLEUKIN-1 AND TUMOR-NECROSIS-FACTOR STIMULATE ARACHIDONIC-ACID RELEASE AND PHOSPHOLIPID-METABOLISM IN HUMAN MYOMETRIAL CELLS SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 13TH ANNUAL MEETING OF THE SOC-OF-PERINATAL-OBSTETRICIANS CY FEB 08-13, 1993 CL SAN FRANCISCO, CA SP SOC PERINATAL OBSTETRICIANS DE CYTOKINES; HUMAN MYOMETRIUM; PRETERM LABOR; ARACHIDONIC ACID ID CYCLOOXYGENASE; CALCIUM; SIGNAL AB OBJECTIVE: Our aim was to evaluate the effects of the cytokines interleukin-1 and tumor necrosis factor on arachidonic acid release in human myometrial cells. STUDY DESIGN: Primary monolayer cultures of human myometrial cells prelabeled with tritiated arachidonic acid were exposed to interleukin-1 or tumor necrosis factor for varying periods and the release of tritiated arachidonic acid and its loss from phospholipids were measured by radiochromatography. To gain some information on the biologic action of interleukin-1 the contractile response to oxytocin was measured in myometrial strips preincubated with this cytokine. Data were statistically evaluated with analysis of variance or Student's t test. RESULTS: Both cytokines caused a dose-dependent increase in tritiated arachidonate release that was suppressed by the protein synthesis inhibitor cycloheximide. Tritiated arachidonic acid release was maximal after 24 hours of stimulation with interleukin-1. Both interleukin-1 and tumor necrosis factor stimulated the release of the isotopically labeled fatty acid from phosphatidylcholine. In addition, interleukin-1 also increased the loss of arachidonic acid from phosphatidic acid and significantly potentiated the oxytocin-evoked myometrial contractility. CONCLUSIONS: Both interleukin-1 and tumor necrosis factor enhance arachidonic acid release, probably by inducing the synthesis of phospholipase A, and possibly other enzymes involved in the metabolism of phospholipids. In turn, arachidonic acid itself may act as a second messenger, synergizing with other uterotonic agents, as well as serving as the precursor for prostaglandins and various other bioactive eicosanoids. C1 ST LOUIS UNIV,SCH MED,MED CTR,ST MARYS HLTH CTR,DEPT OBSTET & GYNECOL,ST LOUIS,MO 63110. WAYNE STATE UNIV,DEPT OBSTET & GYNECOL,DETROIT,MI 48202. NICHHD,PERINATOL BRANCH,BETHESDA,MD 20892. OI Molnar, Miklos/0000-0001-9231-782X NR 14 TC 66 Z9 68 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 1993 VL 169 IS 4 BP 825 EP 829 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA MC458 UT WOS:A1993MC45800010 PM 8238136 ER PT J AU ROMERO, R YOON, BH MAZOR, M GOMEZ, R GONZALEZ, R DIAMOND, MP BAUMANN, P ARANEDA, H KENNEY, JS COTTON, DB SEHGAL, P AF ROMERO, R YOON, BH MAZOR, M GOMEZ, R GONZALEZ, R DIAMOND, MP BAUMANN, P ARANEDA, H KENNEY, JS COTTON, DB SEHGAL, P TI A COMPARATIVE-STUDY OF THE DIAGNOSTIC PERFORMANCE OF AMNIOTIC-FLUID GLUCOSE, WHITE BLOOD-CELL COUNT, INTERLEUKIN-6, AND GRAM STAIN IN THE DETECTION OF MICROBIAL INVASION IN PATIENTS WITH PRETERM PREMATURE RUPTURE OF MEMBRANES SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 13TH ANNUAL MEETING OF THE SOC-OF-PERINATAL-OBSTETRICIANS CY FEB 08-13, 1993 CL SAN FRANCISCO, CA SP SOC PERINATAL OBSTETRICIANS DE INTERLEUKIN-6; AMNIOTIC FLUID; GRAM STAIN; PRETERM LABOR; CYTOKINES; PRETERM PREMATURE RUPTURE OF MEMBRANES; WHITE BLOOD CELL COUNT; GLUCOSE CONCENTRATION ID TUMOR-NECROSIS-FACTOR; INTRAAMNIOTIC INFECTION; LEUKOCYTE ESTERASE; LABOR; AMNIOCENTESIS; WOMEN; PARTURITION; TERM; CHORIOAMNIONITIS; GESTATION AB OBJECTIVE: Our aim was to compare the value of amniotic fluid tests for the detection of microbial invasion of the amniotic cavity and in the prediction of the amniocentesis-to-delivery interval and neonatal complications in patients with preterm premature rupture of membranes. STUDY DESIGN: Amniotic fluid was obtained by transabdominal amniocentesis from 110 consecutive patients with preterm premature rupture of membranes. Fluid was cultured for aerobic and anaerobic bacteria, as well as mycoplasmas. Amniotic fluid analysis included a Gram stain examination, white blood cell count, and glucose and interleukin-6 determinations. Logistic regression and survival techniques (proportional hazards model) were used for statistical analysis. RESULTS: (1) The prevalence of positive amniotic fluid cultures in patients with preterm premature rupture of membranes was 38% (42/110); (2) patients with microbial invasion had a shorter amniocentesis-to-delivery interval and a higher neonatal complication rate than patients with negative cultures; (3) the most sensitive test for the detection of microbial invasion of the amniotic cavity was amniotic fluid interleukin-6 determinations (cutoff 7.9 ng/ml) (sensitivity: for IL-6 80.9%; for white blood cell count 57.1 %; for glucose 57.1 %; for Gram stain 23.8%; p < 0.05 for all comparisons); (4) the most specific test for the detection of microbial invasion was the Gram stain of amniotic fluid (specificity: for Gram stain 98.5%; for white blood cell count 77.9%; for interleukin-6 75%; for glucose 73.5%; p < 0.01 for all); (5) of all amniotic fluid tests, interleukin-6 determination was the only test that had significant clinical value in the prediction of the amniocentesis-to-delivery interval and neonatal complications. CONCLUSION: Interleukin-6 concentrations in amniotic fluid are a better predictor of microbial invasion of the amniotic cavity, amniocentesis-to-delivery interval and neonatal complications than the amniotic fluid Gram stain, glucose, or white blood cell count in patients with preterm premature rupture of membranes. C1 SEOUL NATL UNIV,SEOUL 151,SOUTH KOREA. BEN GURION UNIV NEGEV,SOROKA MED CTR,IL-84105 BEER SHEVA,ISRAEL. VANDERBILT UNIV,NASHVILLE,TN 37240. SYNTEX INC,INST IMMUNOL & BIOL SCI,PALO ALTO,CA 94304. NEW YORK MED COLL,VALHALLA,NY 10595. NICHHD,PERINATOL BRANCH,BETHESDA,MD 20892. RP ROMERO, R (reprint author), WAYNE STATE UNIV,HUTZEL HOSP,SCH MED,DEPT OBSTET & GYNECOL,4707 ST ANTOINE BLVD,DETROIT,MI 48201, USA. RI Yoon, Bo Hyun/H-6344-2011; OI Diamond, Michael/0000-0001-6353-4489 FU NIAID NIH HHS [AI-16262] NR 31 TC 241 Z9 246 U1 0 U2 4 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 1993 VL 169 IS 4 BP 839 EP 851 PG 13 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA MC458 UT WOS:A1993MC45800013 PM 7694463 ER PT J AU PEARSON, JL COWAN, PA COWAN, CP COHN, DA AF PEARSON, JL COWAN, PA COWAN, CP COHN, DA TI ADULT ATTACHMENT AND ADULT-CHILD OLDER-PARENT RELATIONSHIPS SO AMERICAN JOURNAL OF ORTHOPSYCHIATRY LA English DT Article ID AGING PARENTS; LATER LIFE; EXPERIENCE; REPRESENTATION; DEPRESSION; DAUGHTERS; PATTERNS; INFANCY; MOTHERS; AID AB Adult attachment status, concurrent and early relationships with parents, and depressive symptoms were assessed in 53 adults. Individuals with consistent reports of relationships-positive or negative-were most coherent in their narratives. Depressive symptoms were associated with negativity in both recalled and current relationships with parents, but were not correlated with coherence of narratives. Clinical implications of the findings are discussed C1 UNIV CALIF BERKELEY,BERKELEY,CA 94720. UNIV VIRGINIA,CHARLOTTESVILLE,VA 22903. RP PEARSON, JL (reprint author), NIMH,ROCKVILLE,MD 20857, USA. FU NIMH NIH HHS [NIMH RO1MH-31109, NIMH T32MH-18626] NR 46 TC 9 Z9 9 U1 1 U2 1 PU AMER ORTHOPSYCHIATRIC ASSN PI NEW YORK PA 19 W 44TH ST, NEW YORK, NY 10036 SN 0002-9432 J9 AM J ORTHOPSYCHIAT JI Am. J. Orthopsychiatr. PD OCT PY 1993 VL 63 IS 4 BP 606 EP 613 DI 10.1037/h0079471 PG 8 WC Psychiatry; Social Work SC Psychiatry; Social Work GA ME246 UT WOS:A1993ME24600014 PM 8267101 ER PT J AU KUSANO, K GAINER, H BATTEY, JF FATHI, Z WADA, E AF KUSANO, K GAINER, H BATTEY, JF FATHI, Z WADA, E TI RECEPTOR-ACTIVATED CURRENTS IN MOUSE FIBROBLASTS EXPRESSING TRANSFECTED BOMBESIN RECEPTOR SUBTYPE CDNAS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE BALB/C 3T3 CELLS; BOMBESIN; GASTRIN-RELEASING PEPTIDE; NEUROMEDIN-B; GASTRIN-RELEASING PEPTIDE BOMBESIN RECEPTOR ANTAGONISTS ID GASTRIN-RELEASING PEPTIDE; SWISS 3T3 CELLS; CLONING AB BALB/c 3T3 cells do not normally express receptors for bombesin-like peptides [bombesin (Bn), gastrin-releasing peptide (GRP), and neuromedin B (NmB)]. Trnasfection of BALB/c 3T3 cells with complementary DNA-encoding GRP receptors or NmB receptors leads to stable expression of functional GRP receptors (GRP R(t)) or NmB receptors (NmB R(t)), respectively, which are coupled to cell membrane ion channels. Whole cell current analysis using patch electrodes shows that the activation of these newly expressed receptors induces cation conductance increases, most frequently a Ca2+-activated plasma membrane K-conductance. The dose-response (peak-current) relations of both transfected receptor subtypes were sigmoidal and exhibited threshold activation concentration in the picomole range and the saturation of responses to higher concentrations than 10(-8) M. The GRP R(t) responded about equally to GRP, NmB, and Bn when compared at equimolar levels, despite their known difference in binding affinity for the three peptides (GRP, Bn > NmB). In contrast, for the NmB R(t), the NmB was more potent than GRP or Bn. Among four GRP/Bn-receptor antagonists tested, the [D-Phe6]Bn(6-13) ethyl ester suppressed GRP R(t) responses at low concentrations (10(-7) M). N-acetyl-GRP-(20-26) amide, [Leu13-PSI(CH2NH)-Leu14]Bn, and [D-Arg1,D-Phe5,D-Trp7,9,Leu11]substance P also blocked GRP R, responses but at higher concentrations (10(-5) M). However, at these concentrations, these four antagonists had little effect on NmB R(t) responses, thereby showing a specificity of these antagonists for the GRP receptors. C1 NCI,BIOL CHEM LAB,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. RP KUSANO, K (reprint author), NINCDS,NEUROCHEM LAB,BLDG 36,4D-20,BETHESDA,MD 20892, USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD OCT PY 1993 VL 265 IS 4 BP C869 EP C876 PN 1 PG 8 WC Physiology SC Physiology GA ME480 UT WOS:A1993ME48000002 PM 8238311 ER PT J AU MURPHY, E FRALIX, TA LONDON, RE STEENBERGEN, C AF MURPHY, E FRALIX, TA LONDON, RE STEENBERGEN, C TI EFFECTS OF ADENOSINE ANTAGONISTS ON HEXOSE UPTAKE AND PRECONDITIONING IN PERFUSED RAT-HEART SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE CALCIUM; INTRACELLULAR PH; ISCHEMIA; 5,5'-DIFLURO-1,2-BIS(2-AMINOPHENOXY)ETHANE-N,N,N',N'-TETRAACETIC ACID; NUCLEAR MAGNETIC RESONANCE; GLUCOSE TRANSPORT ID NUCLEAR-MAGNETIC-RESONANCE; MYOCARDIAL ISCHEMIA; F-19 NMR; INHIBITION; RECEPTORS; PROTECTION; CHELATORS; RECOVERY; ALTER AB Preconditioning with brief intermittent periods of ischemia has been shown to lessen the detrimental effects of a subsequent sustained (30-60 min) period of ischemia. Because adenosine has been suggested to be the mediator of preconditioning, we were interested in investigating whether adenosine antagonists would block the effect of preconditioning on ionic changes during ischemia. We found that 10 muM of the adenosine antagonist BW-Al433U did not reverse the effect of preconditioning on intracellular pH (pH(i)). Hearts preconditioned with BW-Al433U had virtually no decrease in pH(i) during the 30-min sustained period of ischemia; after 30 min of ischemia, the pH in untreated hearts was 5.97 +/- 0.16 compared with 6.52 +/- 0.10 in preconditioned hearts and 6.90 +/- 0.08 in hearts preconditioned plus BW-Al433U. Because anaerobic glycolysis is largely responsible for the fall in pH(i) during ischemia, we examined the effect of BW-Al433U [and other adenosine antagonists, such as PD-115,199 and 8-cyclopentyl-1,3-dipropylxanthine (CPDPX)] on glucose uptake and phosphorylation during aerobic perfusion using P-31-nuclear magnetic resonance to monitor uptake and phosphorylation of 2-deoxyglucose (2-DG) to 2-deoxyglucose 6-phosphate (2-DG-6-P) when one-half of the glucose in the perfusate was replaced with 2-DG. Uptake of 2-DG-6-P after 15 min was reduced by 66% in the presence of BW-Al433U and 82% in the presence of PD-115,199 as compared with untreated hearts, but was not reduced in the presence of CPDPX. Thus CPDPX was the only adenosine antagonist tested that did not block accumulation of 2-DG-6-P. We also found that CPDPX did not block the beneficial effect of preconditioning on ionic alterations during a sustained 30-min period of ischemia or the improved recovery of function on reflow. C1 DUKE UNIV,MED CTR,DEPT PATHOL,DURHAM,NC 27710. RP MURPHY, E (reprint author), NIEHS,MOLEC BIOPHYS LAB,MD 4A-01,RES TRIANGLE PK,NC 27709, USA. NR 36 TC 22 Z9 22 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD OCT PY 1993 VL 265 IS 4 BP C1146 EP C1155 PN 1 PG 10 WC Physiology SC Physiology GA ME480 UT WOS:A1993ME48000032 ER PT J AU ZIEGELSTEIN, RC CHENG, L BLANK, PS SPURGEON, HA LAKATTA, EG HANSFORD, RG CAPOGROSSI, MC AF ZIEGELSTEIN, RC CHENG, L BLANK, PS SPURGEON, HA LAKATTA, EG HANSFORD, RG CAPOGROSSI, MC TI MODULATION OF CALCIUM HOMEOSTASIS IN CULTURED RAT AORTIC ENDOTHELIAL-CELLS BY INTRACELLULAR ACIDIFICATION SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE CYTOSOLIC PH; ACID-BASE EQUILIBRIUM; INDO 1; CARBOXY-SEMINAPHTHORHODAFLUOR-1; ACIDOSIS ID FLUORESCENT CALCIUM; PH; MOBILIZATION; FURA-2; INDICATORS; MYOCYTES; ARTERIES AB Acidosis produces vasodilation in a process that may involve the vascular endothelium. Because synthesis and release of endothelium-derived vasodilatory substances are linked to an increase in cytosolic calcium concentration ([Ca2+]i), we examined the effect of intracellular acidification on cultured rat aortic endothelial cells loaded either with the pH-sensitive probe carboxy-seminaphthorhodafluor-1 or the Ca2+-sensitive fluorescent probe indo 1. The basal cytosolic pH (pH(i)) of endothelial monolayers in a 5% CO2-HCO3- buffer was 7.27 +/- 0.02 and that in a bicarbonate-free solution was 7.22 +/- 0.03. Acidification was induced either by removal of NH4Cl (DELTApH(i) = -0.10 +/- 0.02), changing from a bicarbonate-free to a 5% CO2-HCO3-buffered solution at constant buffer pH (DELTApH(i) = -0.18 +/- 0.03), or changing from a 5% to a 20% CO2-HCO3- solution (DELTApH(i) = -0.27 +/- 0.07). Regardless of the method used, intracellular acidification increased [Ca2+]i as indexed by indo 1 fluorescence. The increase in [Ca2+]i induced by changing from a 5 to a 20% CO2-HCO3- solution was not significantly altered by removal of buffer Ca2+ either before or after depletion of bradykinin- and thapsigargin-sensitive intracellular Ca2+ stores. Thus intracellular acidification of vascular endothelial cells releases Ca2+ into the cytosol either from pH-sensitive intracellular buffer sites, mitochondria, or from bradykinin- and thapsigargin-insensitive intracellular stores. This Ca2+ mobilization may be linked to endothelial synthesis and release of vasodilatory substances during acidosis. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,DEPT MED,DIV CARDIOL,BALTIMORE,MD 21205. NR 35 TC 54 Z9 54 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD OCT PY 1993 VL 265 IS 4 BP H1424 EP H1433 PN 2 PG 10 WC Physiology SC Physiology GA ME481 UT WOS:A1993ME48100052 ER PT J AU LEVINE, SJ LARIVEE, P LOGUN, C ANGUS, CW SHELHAMER, JH AF LEVINE, SJ LARIVEE, P LOGUN, C ANGUS, CW SHELHAMER, JH TI CORTICOSTEROIDS DIFFERENTIALLY REGULATE SECRETION OF IL-6, IL-8, AND G-CSF BY A HUMAN BRONCHIAL EPITHELIAL-CELL LINE SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE BRONCHIAL EPITHELIUM; CYTOKINES; INTERLEUKINS; CORTICOSTEROIDS; REVERSE-TRANSCRIPTION POLYMERASE CHAIN REACTION; GRANULOCYTE COLONY-STIMULATING FACTOR ID COLONY-STIMULATING FACTOR; ENDOTHELIAL-CELLS; HUMAN-NEUTROPHILS; ARACHIDONIC-ACID; GENE-EXPRESSION; INTERLEUKIN-6; DEXAMETHASONE; GLUCOCORTICOIDS; FIBROBLASTS; ACTIVATION AB Human airway epithelial cells play an active role in modulating airway inflammation by elaborating a variety of proinflammatory molecules, including cytokines. The purpose of this study was to define the role of corticosteroids in the regulation of cytokine gene transcription and secretion by human bronchial epithelial cells. In particular, we assessed whether dexamethasone was capable of inhibiting the tumor necrosis factor-alpha (TNF-alpha)-mediated secretion of interleukin-6 (IL-6), interleukin-8 (IL-8), and granulocyte colony-stimulating factor (G1-CSF) by a human bronchial epithelial cell line (BEAS-2B). Stimulation with 20 ng/ml of TNF-alpha resulted in significant increases in secretion of immunoreactive IL-6, IL-8, and G-CSF that were maximal at 24 h. TNF-alpha-mediated IL-6, IL-8, and G-CSF secretion was concentration dependent and specific. In addition, stimulation with TNF-alpha resulted in significant increases in the quantity of IL-6, IL-8, and G-CSF mRNA as detected by reverse-transcription polymerase chain reaction. Dexamethasone preconditioning significantly inhibited both the secretion of immunoreactive IL-6 and the accumulation of IL-6 mRNA. Although dexamethasone appeared to reduce both the secretion of immunoreactive IL-8 and accumulation of IL-8 mRNA, the inhibitory effects did not reach statistical significance. Finally, dexamethasone did not inhibit either the secretion of immunoreactive G-CSF or the accumulation of G-CSF mRNA. In summary, our results suggest that corticosteroids have a differential effect on the regulation of cytokine secretion by human bronchial epithelial cells. Although corticosteroids may ameliorate airway inflammation by inhibition of IL-6 secretion, dexamethasone did not prevent the TNF-alpha-mediated increases in IL-8 and G-CSF secretion. This represents a potential mechanism by which corticosteroids may fail to downregulate the chemotaxis, activation, and survival of neutrophils in inflammatory airway disorders. These cytokine pathways and their regulatory mechanisms may have important roles in the pathogenesis and therapy of inflammatory airway disorders. RP LEVINE, SJ (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BETHESDA,MD 20892, USA. NR 42 TC 74 Z9 74 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD OCT PY 1993 VL 265 IS 4 BP L360 EP L368 PN 1 PG 9 WC Physiology SC Physiology GA ME480 UT WOS:A1993ME48000088 PM 7694480 ER PT J AU WEHR, TA MOUL, DE BARBATO, G GIESEN, HA SEIDEL, JA BARKER, C BENDER, C AF WEHR, TA MOUL, DE BARBATO, G GIESEN, HA SEIDEL, JA BARKER, C BENDER, C TI CONSERVATION OF PHOTOPERIOD-RESPONSIVE MECHANISMS IN HUMANS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE PHOTOPERIODISM; SEASONS; CIRCADIAN RHYTHM; LIGHT; SLEEP; MELATONIN; PROLACTIN; THYROTROPIN; GROWTH HORMONE; CORTISOL; LUTEINIZING HORMONE; TESTOSTERONE; BODY TEMPERATURE ID CIRCADIAN-RHYTHM; PLASMA-CONCENTRATIONS; MELATONIN SECRETION; HUMAN SLEEP; PROLACTIN; PACEMAKER; TIME; DAYLENGTH; SEASONS; SYSTEM AB In animals, circadian pacemakers respond to seasonal changes in day length by making corresponding adjustments in the durations of diurnal and nocturnal periods of circadian rhythms; these adjustments mediate effects of photoperiod on breeding and other seasonally recurring phenomena. Little is known about photoperiod responses of human circadian pacemakers. To investigate this question, we recorded and compared circadian rhythm profiles of 15 individuals after chronic exposures to short (8 h) and long (14 h) nights. As occurs in animals, durations of nocturnal periods of active melatonin secretion (11.9 +/- 1.6 vs. 10.3 +/- 1.3 h, df = 14, t = 4.583, P < 0.0005, paired t test), high prolactin secretion (12.9 +/- 2.1 vs. 9.9 +/- 2.2 h, df = 11, t = 2.917, P < 0.01), and sleep (10.6 +/- 0.8 vs. 7.6 +/- 0.4 h, df = 14, t = 17.122, P < 0.0005) were longer after exposure to long nights than after short ones. Durations of nocturnal periods of low rectal temperature (11.6 +/- 2.3 vs. 9.5 +/- 1.6 h, df = 12, t = 3.912, P < 0.001) and rising cortisol secretion (10.8 +/- 1.6 vs. 9.3 +/- 1.9 h, df = 14, t = 3.130, P < 0.005) were also longer. Some of these differences persisted during 24-h periods of enforced wakefulness in constant dim light, indicating that prior exposure to the two regimes induced abiding changes in the timing of internal processes, such as circadian pacemaker oscillations, that control the durations of nocturnal and diurnal periods of the rhythms. RP WEHR, TA (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,RM 45-239,BLDG 10,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 34 TC 182 Z9 183 U1 1 U2 9 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD OCT PY 1993 VL 265 IS 4 BP R846 EP R857 PN 2 PG 12 WC Physiology SC Physiology GA ME481 UT WOS:A1993ME48100081 PM 8238456 ER PT J AU PARDES, H AF PARDES, H TI THE REPORT OF THE NATIONAL-ADVISORY-MENTAL-HEALTH-COUNCIL SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material C1 NIMH,BETHESDA,MD 20892. NR 0 TC 3 Z9 3 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 1993 VL 150 IS 10 BP 1445 EP 1446 PG 2 WC Psychiatry SC Psychiatry GA MA342 UT WOS:A1993MA34200002 PM 8379546 ER PT J AU YANOVSKI, SZ NELSON, JE DUBBERT, BK SPITZER, RL AF YANOVSKI, SZ NELSON, JE DUBBERT, BK SPITZER, RL TI ASSOCIATION OF BINGE-EATING DISORDER AND PSYCHIATRIC COMORBIDITY IN OBESE SUBJECTS SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID LIFETIME PREVALENCE; BULIMIA-NERVOSA; GASTRIC BYPASS; SEXUAL ABUSE; POPULATION; ANOREXIA AB Objective: The authors determined the prevalence of binge eating disorder in a self-referred study group of moderately and severely obese subjects and investigated whether binge eating disorder was associated with psychiatric disorders, a history of psychotherapy, a family history of psychiatric illness, or a history of sexual abuse. Method: They interviewed 89 obese women and 39 obese men (body mass index > 30 kg/m2) who were not currently in weight loss treatment, using the Binge Eating Disorder Clinical Interview, the Structured Clinical Interview for DSM-III-R, and the Structured Clinical Interview for DSM-III-R Personality Disorders. Results: Forty-three (34%) of the subjects met criteria for binge eating disorder-33 women and 10 men. Black and white subjects had similar rates of binge eating disorder. Subjects with binge eating disorder were significantly more likely than those without the disorder to have a lifetime prevalence of a DSM-III-R axis I or axis II diagnosis and to have undergone psychotherapy or counseling. The lifetime rates of major depression, panic disorder, bulimia nervosa, borderline personality disorder, and avoidant personality disorder were all significantly higher in subjects with binge eating disorder. The rate of reported sexual abuse was not higher among subjects with binge eating disorder; however, they were significantly more likely to have a family history of substance abuse. The relative risks for psychiatric disorders were higher in both moderately and severely obese subjects with binge eating disorder than in those without the disorder. Conclusions: Among both moderately and severely obese subjects, binge eating disorder is associated with higher rates of axis I and axis II psychiatric disorders. C1 NIDDKD,DIV DIGEST DIS & NUTR,ROCKVILLE,MD. COLUMBIA UNIV COLL PHYS & SURG,NEW YORK,NY 10032. RP YANOVSKI, SZ (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,BLDG 10,3-S231,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 35 TC 338 Z9 347 U1 5 U2 18 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 1993 VL 150 IS 10 BP 1472 EP 1479 PG 8 WC Psychiatry SC Psychiatry GA MA342 UT WOS:A1993MA34200005 PM 8379549 ER PT J AU BIGGAR, RJ AF BIGGAR, RJ TI WHEN IDEALS MEET REALITY - THE GLOBAL CHALLENGE OF HIV AIDS SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. NR 5 TC 4 Z9 4 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD OCT PY 1993 VL 83 IS 10 BP 1383 EP 1384 DI 10.2105/AJPH.83.10.1383 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA MA606 UT WOS:A1993MA60600003 PM 8214224 ER PT J AU SIMONSICK, EM LAFFERTY, ME PHILLIPS, CL DELEON, CFM KASL, SV SEEMAN, TE FILLENBAUM, G HEBERT, P LEMKE, JH AF SIMONSICK, EM LAFFERTY, ME PHILLIPS, CL DELEON, CFM KASL, SV SEEMAN, TE FILLENBAUM, G HEBERT, P LEMKE, JH TI RISK DUE TO INACTIVITY IN PHYSICALLY CAPABLE OLDER ADULTS SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CORONARY HEART-DISEASE; HEALTH PRACTICES; GLUCOSE-TOLERANCE; FOLLOW-UP; MEN; MORTALITY; EXERCISE; DENSITY; YOUNG; WOMEN AB Objectives. This study examined the association between recreational physical activity among physically capable older adults and functional status, incidence of selected chronic conditions, and mortality over 3 and 6 years. Methods. Data are from three sites of the Established Populations for Epidemiologic Studies of the Elderly. Results. A high level of recreational physical activity reduced the likelihood of mortality over both 3 and 6 years. Moderate to high activity reduced the risk of physical impairments over 3 years; this effect diminishes after 6 years. A consistent relationship between activity and new myocardial infarction or stroke or the incidence of diabetes or angina was not found after 3 or 6 years. Conclusions. Findings suggest that physical activity offers benefits to physically capable older adults, primarily in reducing the risk of functional decline and mortality. Future work must use more objective and quantifiable measures of activity and assess changes in activity levels over time. C1 DUKE UNIV,MED CTR,CTR STUDY AGING & HUMAN DEV,DURHAM,NC 27710. BRIGHAM & WOMENS HOSP,DEPT MED,CAMBRIDGE,MA. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. UNIV IOWA,DEPT PREVENT MED,IOWA CITY,IA 52242. RP SIMONSICK, EM (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,7201 WISCONSIN AVE,GATEWAY BLDG,BETHESDA,MD 20892, USA. NR 37 TC 176 Z9 178 U1 1 U2 6 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD OCT PY 1993 VL 83 IS 10 BP 1443 EP 1450 DI 10.2105/AJPH.83.10.1443 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA MA606 UT WOS:A1993MA60600016 PM 8214236 ER PT J AU PHILPOT, RM AF PHILPOT, RM TI MODULATION OF THE PULMONARY CYTOCHROME-P450 SYSTEM AS A FACTOR IN PULMONARY-SELECTIVE TOXIC RESPONSES - FACT AND FICTION SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Editorial Material ID RABBIT LUNG; MONOOXYGENASE; XENOBIOTICS; METABOLISM; LIVER RP PHILPOT, RM (reprint author), NIEHS,CELLULAR & MOLEC PHARMACOL LAB,MOLEC PHARMACOL SECT,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 11 TC 10 Z9 10 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD OCT PY 1993 VL 9 IS 4 BP 347 EP 349 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA MA816 UT WOS:A1993MA81600001 PM 8398173 ER PT J AU TRAVIS, WD BOROK, Z ROUM, JH ZHANG, J FEUERSTEIN, I FERRANS, VJ CRYSTAL, RG AF TRAVIS, WD BOROK, Z ROUM, JH ZHANG, J FEUERSTEIN, I FERRANS, VJ CRYSTAL, RG TI PULMONARY LANGERHANS CELL GRANULOMATOSIS (HISTIOCYTOSIS-X) - A CLINICOPATHOLOGICAL STUDY OF 48 CASES SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE LANGERHANS CELL GRANULOMATOSIS; EOSINOPHILIC GRANULOMA; LUNG; EOSINOPHILIC PLEURITIS; HIGH RESOLUTION COMPUTERIZED TOMOGRAPHY; CIGARETTE SMOKE; NEUROFIBROMATOSIS ID DESQUAMATIVE INTERSTITIAL PNEUMONIA; REACTIVE EOSINOPHILIC PLEURITIS; BRONCHOALVEOLAR LAVAGE FLUID; HIGH-RESOLUTION CT; CIGARETTE-SMOKING; DENDRITIC CELLS; LUNG-DISEASE; IMMUNOCYTOCHEMICAL CHARACTERIZATION; INTRALUMINAL FIBROSIS; MONOCLONAL-ANTIBODY AB We report the clinical and histologic findings of lung biopsies from 48 patients with pulmonary Langerhans cell granulomatosis (PLCG) and show how special techniques such as immunohistochemistry, electron microscopy (EM), and high resolution computerized tomography (HRCT) of the lungs can be useful in diagnostically challenging cases. Nineteen patients were men and 29 were women. The median age was 33 years (range 15-54 years). Two had pituitary involvement. Bone lesions were observed in four patients and biopsy proven in two. All patients were cigarette smokers. In six patients HRCT revealed a combination of thin-walled cystic and nodular lesions. The pathologic diagnosis was established on the basis of open lung biopsy specimens in 44 cases and transbronchial biopsy specimens in 4 of 10 cases. In two transbronchial biopsies, diagnostic PLCG infiltrates were seen in toluidine blue-stained thick sections in the tissue processed for EM but not on the tissue processed for histology. EM in both of these cases revealed Birbeck granules within LCs. The diagnosis was supported by a positive bone biopsy in one of these patients and characteristic HRCT findings in the other. The antibody to S100 protein stained the LC infiltrates in the five cases studied. This staining and the characteristic findings on HRCT confirmed the diagnosis in one case in which the PLCG lesions were obscured by atelectasis. The frequent finding of intraluminal fibrosis (78% of open lung biopsies) supports the recent suggestion that this alteration plays an important role in the pathogenesis of fibrotic remodeling in PLCG. The strong association of PLCG with cigarette smoking and the frequent peribronchiolar location of PLCG lesions (87% of open lung biopsies) in our cases are consistent with the concept that in adults this disorder is associated with an abnormal response to cigarette smoke. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NHLBI,PULM BRANCH,BETHESDA,MD 20892. NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NIH,WARREN MAGNUSON CLIN CTR,DEPT RADIOL,BETHESDA,MD 20892. NR 63 TC 166 Z9 173 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 1993 VL 17 IS 10 BP 971 EP 986 DI 10.1097/00000478-199310000-00002 PG 16 WC Pathology; Surgery SC Pathology; Surgery GA LZ182 UT WOS:A1993LZ18200002 PM 8372949 ER PT J AU KUMAR, S KUMAR, D KINGMA, DW JAFFE, ES AF KUMAR, S KUMAR, D KINGMA, DW JAFFE, ES TI EPSTEIN-BARR-VIRUS ASSOCIATED T-CELL LYMPHOMA IN A RENAL-TRANSPLANT PATIENT SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Note DE T-CELL LYMPHOMA; TRANSPLANT RECIPIENT; IMMUNOPHENOTYPING; GENOTYPING; EPSTEIN-BARR VIRUS; REVIEW ID EMBEDDED TISSUE-SECTIONS; NON-HODGKINS LYMPHOMA; MONOCLONAL-ANTIBODIES; GENE REARRANGEMENTS; PARAFFIN SECTIONS; B-CELL; ANTIGEN; PHENOTYPE; IMMUNOGLOBULIN; MALIGNANCIES AB Posttransplant lymphoproliferative disorders in organ allograft recipients are most commonly of B cell origin, whereas T cell lymphomas are rarely described. We report a case of T cell immunoblastic large cell lymphoma associated with Epstein-Barr virus (EBV) that occurred in a recipient of a cadaveric renal transplant 7 years post-transplantation. On paraffin immunophenotyping, none of the neoplastic cells stained with the T cell-associated markers used, but did show strong CD30 expression. Flow cytometric studies revealed a predominance of T cells without definite evidence of T cell neoplasia. Frozen section immunophenotyping studies revealed a T cell phenotype with aberrant expression, and genotypic studies demonstrated T cell receptor beta gene rearrangement with germline configuration of immunoglobulin heavy chain and kappa light chain genes, confirming a T lineage. EBV-encoded RNA transcripts were demonstrated within the neoplastic cells by in situ hybridization. Southern blot analysis using probes derived from the terminal repeat region of the virus detected a single restriction band indicating a clonal population. We believe this is the first case of a posttransplant T cell lymphoma in which the EBV genome has been demonstrated. This case also illustrates the pitfalls of paraffin immunophenotyping in the diagnosis of T cell lymphoma. C1 NIH,DEPT PATHOL,BETHESDA,MD 20892. RP KUMAR, S (reprint author), UNIV TEXAS,MED BRANCH,DEPT PATHOL,DIV SURG PATHOL,E-88,GALVESTON,TX 77555, USA. NR 38 TC 51 Z9 51 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 1993 VL 17 IS 10 BP 1046 EP 1053 DI 10.1097/00000478-199310000-00010 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA LZ182 UT WOS:A1993LZ18200010 PM 8396856 ER PT J AU HOLLINGSWORTH, HC JAFFE, ES AF HOLLINGSWORTH, HC JAFFE, ES TI EPITHELIOID GRANULOMAS IN SMALL NONCLEAVED CELL LYMPHOMA - REPLY SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Letter RP HOLLINGSWORTH, HC (reprint author), NCI,PATHOL LAB,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 1993 VL 17 IS 10 BP 1068 EP 1068 PG 1 WC Pathology; Surgery SC Pathology; Surgery GA LZ182 UT WOS:A1993LZ18200016 ER PT J AU DARWISH, MA RAOUF, TA RUSHDY, P CONSTANTINE, NT RAO, MR EDELMAN, R AF DARWISH, MA RAOUF, TA RUSHDY, P CONSTANTINE, NT RAO, MR EDELMAN, R TI RISK-FACTORS ASSOCIATED WITH A HIGH SEROPREVALENCE OF HEPATITIS-C VIRUS-INFECTION IN EGYPTIAN BLOOD-DONORS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID NON-B-HEPATITIS; HEPATOCELLULAR-CARCINOMA; NON-A; SCHISTOSOMA-MANSONI; PREVALENCE; RESPONSES; HCV; EPIDEMIOLOGY; ANTIBODIES; CIRRHOSIS AB We performed serologic tests for hepatitis C virus (HCV) infection on sera obtained from 163 volunteer blood donors seen at one Cairo hospital. We found HCV infection in 36 donors (22%) measured by a second generation enzyme immunoassay. Thirty-five of these 36 positive sera were tested with a second generation recombinant immunoblot assay (RIBA-2); 22 (63%) were reactive and another 12 (34%) showed an indeterminate reaction. Overall, 13.6% (95% confidence interval [CI] = 8.3-18.9%) of these Egyptian blood donors were serologically confirmed to be infected with HCV. Of several demographic variables and medical risk factors examined, the serologically confirmed (RIBA-2 reactive) donors were significantly older than nonreactive donors, and the age-adjusted risk of being HCV-positive was significantly greater in individuals residing outside Cairo. A knowledge of having received injections, of having a history of schistosomiasis, or of having concomitant hepatitis B surface antigen or antibody were significantly associated with an increased risk of HCV-seropositivity; however, after adjusting for confounding demographic factors, only schistosomiasis (odds ratio = 8.9, 95% CI = 2.35-33.52) was significantly associated with HCV infection. The HCV seropositive rate of 13.6% among Egyptians is 5-35-fold higher than that reported from volunteer blood donors in other countries. Screening for HCV should be instituted in Egyptian blood banks. Blood banks that do not test for HCV should include a history of schistosomiasis in their exclusion criteria used for routine screening of blood donors. C1 UNIV MARYLAND,SCH MED,CTR VACCINE DEV,10 S PINE ST,ROOM 9-34,BALTIMORE,MD 21201. AIN SHAMS UNIV,FAC MED,DEPT MICROBIOL,CAIRO,EGYPT. MANCHIET EL BAKREY HOSP,CAIRO,EGYPT. UNIV MARYLAND,SCH MED,DEPT PATHOL,BALTIMORE,MD 21201. NICHHD,EPIDEMIOL BRANCH,ROCKVILLE,MD 20852. UNIV MARYLAND,SCH MED,DEPT MED,DIV GEOG MED,BALTIMORE,MD 21201. NR 38 TC 129 Z9 137 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 1993 VL 49 IS 4 BP 440 EP 447 PG 8 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA MD964 UT WOS:A1993MD96400007 PM 7692754 ER PT J AU MCELVANEY, NG DOUJAIJI, B MOAN, MJ BURNHAM, MR WU, MC CRYSTAL, RG AF MCELVANEY, NG DOUJAIJI, B MOAN, MJ BURNHAM, MR WU, MC CRYSTAL, RG TI PHARMACOKINETICS OF RECOMBINANT SECRETORY LEUKOPROTEASE INHIBITOR AEROSOLIZED TO NORMALS AND INDIVIDUALS WITH CYSTIC-FIBROSIS SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Article ID LEUKOCYTE PROTEASE INHIBITOR; AMINO-ACID SEQUENCE; PROTEINASE-INHIBITOR; NEUTROPHIL ELASTASE; HUSI-I; ANTILEUKOPROTEASE; PSEUDOMONAS; LAVAGE; SLPI AB Recombinant secretory leukoprotease inhibitor (rSLPI), a recombinant form of a natural airway inhibitor of neutrophil elastase (NE), is a potential therapeutic agent for cystic fibrosis (CF), a condition characterized by airway derangement mediated in part by the large burden of NE on the CF respiratory epithelial surface. After in vitro studies that demonstrated that aerosolized rSLPI retains its form and function, rSLPI was administered via aerosol to normal individuals and individuals with CF to determine the pharmacokinetics of in vivo rSLPI augmentation of the anti-NE defenses of the respiratory epithelial surface. After rSLPI aerosolization to normal individuals (100 mg single dose or 100 mg twice daily for 1 wk) there was a marked increase in SLPI levels and anti-NE capacity in airway epithelial lining fluid (ELF) at 1 h, diminishing gradually over 4 to 12 h. Interestingly, the ELF SLPI levels and anti-NE capacity achieved 12 h after 1 wk of rSLPI aerosols were no different than those 12 h after a single dose of rSLPI, suggesting that rSLPI does not accumulate on the respiratory epithelial surface after aerosolization. The ability of rSLPI to suppress NE in vivo was evaluated by aerosolization of rSLPI to individuals with CF, first as an escalating dose to assess safety, and then at doses of 100 mg twice daily for 1 wk or 50 mg twice daily for 2 wk. Before aerosol, SLPI levels in ELF of individuals with CF were the same as in normal individuals, but unlike normal individuals, individuals with CF had active NE in ELF (12.4 +/- 3.0 muM) indicating that the SLPI in CF ELF was inactive. After aerosolization of 100 mg rSLPI twice daily for 1 wk there was a reduction in ELF active NE. In contrast, ELF active NE levels were not reduced with 50 mg twice daily, likely due to the failure of this dose regime to sufficiently elevate ELF SLPI levels. These data show that rSLPI is functional after both in vitro and in vivo aerosolization and can significantly suppress the NE burden in the CF lung but must be given regularly and in sufficient quantity to be effective. C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BIOSTAT RES BRANCH,BETHESDA,MD 20892. RP MCELVANEY, NG (reprint author), NHLBI,PULM BRANCH,BLDG 10,ROOM 6D03,BETHESDA,MD 20892, USA. RI McElvaney, Noel/A-6809-2010 NR 25 TC 88 Z9 88 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD OCT PY 1993 VL 148 IS 4 BP 1056 EP 1060 PG 5 WC Respiratory System SC Respiratory System GA MC073 UT WOS:A1993MC07300038 PM 8105734 ER PT J AU BERBERICH, MA BOAT, TF TEPPER, R STECENKO, A STENMARK, K BEALL, R BRADY, A BRUCE, M COALSON, J COATES, A COTTON, RB DANIEL, C DOLOVICH, M ENGLAND, S FAN, L GAULTIER, C GRISCOM, NT MERRITT, TA MORGAN, WJ MOTOYAMA, E PLATZKER, A STRIFE, J WISWELL, T WOHL, ME WOOD, R AF BERBERICH, MA BOAT, TF TEPPER, R STECENKO, A STENMARK, K BEALL, R BRADY, A BRUCE, M COALSON, J COATES, A COTTON, RB DANIEL, C DOLOVICH, M ENGLAND, S FAN, L GAULTIER, C GRISCOM, NT MERRITT, TA MORGAN, WJ MOTOYAMA, E PLATZKER, A STRIFE, J WISWELL, T WOHL, ME WOOD, R TI ASSESSMENT OF LUNG-FUNCTION AND DYSFUNCTION IN STUDIES OF INFANTS AND CHILDREN SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Editorial Material ID CYSTIC-FIBROSIS; BRONCHOPULMONARY DYSPLASIA; PULMONARY-FUNCTION RP BERBERICH, MA (reprint author), NHLBI,DIV LUNG DIS,CELL & DEV BIOL BRANCH,WESTWOOD BLDG,ROOM 6A07,BETHESDA,MD 20892, USA. NR 19 TC 21 Z9 21 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD OCT PY 1993 VL 148 IS 4 BP 1105 EP 1108 PG 4 WC Respiratory System SC Respiratory System GA MC073 UT WOS:A1993MC07300047 ER PT J AU JAFFE, JS METCALFE, DD AF JAFFE, JS METCALFE, DD TI CYTOKINES AND THEIR ROLE IN THE PATHOGENESIS OF SEVERE FOOD HYPERSENSITIVITY REACTIONS SO ANNALS OF ALLERGY LA English DT Article ID MAST-CELLS; EOSINOPHILIC GASTROENTERITIS; SIGNAL TRANSDUCTION; CYCLOSPORINE-A; TNF-ALPHA; MECHANISM AB Cytokines are proteins produced by one cell that are capable of altering the behavior of another cell. Their biologic effects are both pleomorphic and redundant. A number of cytokines have been implicated in the genesis of allergic reactions, including IL-4, IL-5, IL-6, and tumor necrosis factor (TNF). In contrast, other cytokines such as gamma interferon (gamma-IFN) may have biologic actions that act to limit allergic responses. In studies on patients with severe food allergy, we have found cytokine production from peripheral T cells to be abnormal following mitogenic stimulation. These lymphokine abnormalities may contribute to the elevation in IgE and the eosinophilia seen in severe food allergy. C1 NIAID,CLIN INVEST LAB,MAST CELL PHYSIOL SECT,BLDG 10,ROOM 11C210,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 17 TC 5 Z9 5 U1 0 U2 1 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 1993 VL 71 IS 4 BP 362 EP 364 PG 3 WC Allergy SC Allergy GA MB778 UT WOS:A1993MB77800006 PM 8214800 ER PT J AU CHIK, CL FRIEDMAN, A MERRIAM, GR GAHL, WA AF CHIK, CL FRIEDMAN, A MERRIAM, GR GAHL, WA TI PITUITARY-TESTICULAR FUNCTION IN NEPHROPATHIC CYSTINOSIS SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE CYSTINOSIS; KIDNEY TRANSPLANTATION; TESTOSTERONE; KIDNEY FAILURE, CHRONIC; HYPOGONADISM ID PLASMA TESTOSTERONE; HORMONE-SECRETION; LH; COMPLICATIONS; INSUFFICIENCY; HYPOGONADISM; CHILDREN; SUBUNITS; INVITRO; PATIENT AB Objective: To evaluate reproductive function in patients with cystinosis and in renal transplant recipients without cystinosis. Design: Cross-sectional study. Setting: Clinical Center, National Institutes of Health. Patients: Ten male patients, 15 to 28 years old, with nephropathic cystinosis and renal allografts formed the study group; 11 renal transplant recipients who had a primary renal disorder other than cystinosis and were matched with study patients for age and renal function served as the control group. Measurements: Tanner staging, serum gonadotropin determinations, and testosterone and testosterone-binding globulin assessments. Selected patients also had a human chorionic gonadotropin (HCG) stimulation test, a gonadotropin-releasing hormone (GnRH) stimulation test, and serial sampling for luteinizing hormone (LH). Main Results: Although testosterone levels were within normal limits in 7 of 10 patients with cystinosis, the mean testosterone level in patients with cystinosis was 11.5 +/- 2.0 nmol/L compared with 24.2 +/- 3.0 nmol/L in control patients (P < 0.005). No patient with cystinosis reached Tanner stage 5 (full pubertal development), whereas 9 of 11 control patients did. Seven of 10 patients with cystinosis had elevations in LH or follicle-stimulating hormone (FSH) levels, suggesting testicular failure. These patients also had normal LH and FSH responses after GnRH stimulation, increased LH pulse frequency, and reduced testosterone response after HCG stimulation. In comparison, only 3 of 11 control patients had minimally elevated gonadotropin levels, and all 11 had normal testosterone levels. Microscopic testicular examination in one patient showed cystine crystals, germinal dysplasia, increased fibrosis, and Leydig cell hyperplasia. Conclusions: Abnormalities in the pituitary-testicular axis are common in male patients with cystinosis. These changes appear to be related to the disease cystinosis and not to treated renal failure per se. C1 NICHHD,HUMAN GENET BRANCH,BLDG 10,ROOM 95-242,BETHESDA,MD 20892. UNIV WISCONSIN,MADISON,WI 53706. NR 40 TC 39 Z9 40 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 1 PY 1993 VL 119 IS 7 BP 568 EP 575 PN 1 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA MA291 UT WOS:A1993MA29100004 PM 8363167 ER PT J AU ANDRES, R MULLER, DC SORKIN, JD AF ANDRES, R MULLER, DC SORKIN, JD TI LONG-TERM EFFECTS OF CHANGE IN BODY-WEIGHT ON ALL-CAUSE MORTALITY - A REVIEW SO ANNALS OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT CONF ON METHODS FOR VOLUNTARY WEIGHT-LOSS AND CONTROL CY MAR 30-APR 01, 1992 CL BETHESDA, MD SP NIH, NUTR COORDINATING COMM, NIH, OFF MED APPL RES ID GUIDELINES; LONGEVITY; AMERICANS; MEN; VARIABILITY; POPULATION; HEALTH; DEATH; AGE AB Objective: To summarize published studies analyzing the effects of long-term change in body weight on all-cause mortality and have not been reported elsewhere in these proceedings. Data Sources: Thirteen reports from 11 diverse population studies, 7 from the United States and 4 from Europe. Study Selection: All studies included a weight change period of 4 or more years, followed by a mortality assessment period of 8 or more years. All weight changes occurred in persons 17 years or older. Data Extraction: Data from individual studies are presented as number of participants, number of deaths, ages at initial and final weight measurements, duration of the mortality follow-up period, consideration of cigarette smoking and other potential confounders, exclusion criteria, temporal separation between the weight change and mortality follow-up periods, and the association between weight change and all-cause mortality. Data Synthesis: Results are summarized by weight change associated with the lowest mortality rate and by the effects of long-term weight loss on mortality rate. Conclusions: Despite the diversity of the populations studied, the degree of ''clinical clean-up'' at entry, the techniques used to assess weight change, and the differences in analytic techniques (including consideration of potentially confounding variables), certain conclusions may be drawn. Evidence suggests that the highest mortality rates occur in adults who either have lost weight or have gained excessive weight. The lowest mortality rates are generally associated with modest weight gains. RP ANDRES, R (reprint author), NIA,GERONTOL RES CTR,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 21 TC 178 Z9 183 U1 0 U2 3 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 1993 VL 119 IS 7 BP 737 EP 743 PN 2 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA MA330 UT WOS:A1993MA33000022 PM 8363208 ER PT J AU HIGGINS, M DAGOSTINO, R KANNEL, W COBB, J AF HIGGINS, M DAGOSTINO, R KANNEL, W COBB, J TI BENEFITS AND ADVERSE-EFFECTS OF WEIGHT-LOSS - OBSERVATIONS FROM THE FRAMINGHAM-STUDY SO ANNALS OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT CONF ON METHODS FOR VOLUNTARY WEIGHT-LOSS AND CONTROL CY MAR 30-APR 01, 1992 CL BETHESDA, MD SP NIH, NUTR COORDINATING COMM, NIH, OFF MED APPL RES ID BODY-WEIGHT; FOLLOW-UP; CARDIOVASCULAR-DISEASE; MORTALITY; VARIABILITY; LONGEVITY; HEALTH; RISK AB Objective: To identify the benefits and adverse effects of weight loss. Design: Longitudinal, epidemiologic study in a defined population. Participants: Men and women (n = 2500) who were between 35 and 54 years old at baseline, followed for 20 years in Framingham, Massachusetts. Measurements: Height, weight, lipid levels, blood pressure, smoking status, diet, physical activity, prevalent and incident cardiovascular disease, diabetes, other diseases, and mortality rate were assessed. Results: Compared with those whose body mass index (BMI) or weight changed least, men and women who lost weight during a 10-year period were older, heavier, and had higher blood pressures and cholesterol levels initially but had the smallest gains in blood pressure and cholesterol levels. However, rates of cigarette smoking were higher, and rates of smoking cessation were lower. During 20 years of further follow-up, death rates were highest in those whose BMI decreased and in those with the highest BMI at study entry. Relative risks for death from cardiovascular disease, coronary heart disease, and all causes were significantly greater by 33% to 61% in men whose BMI decreased after adjusting for age and risk factors for cardiovascular disease. In women, weight loss and weight gain were associated with higher relative risks for cardiovascular disease and coronary heart disease, but only the 38% increase in total mortality rate among women who lost weight was statistically significant after adjusting for age. Conclusions: Weight loss was associated with improvements in blood pressure and cholesterol levels but also with continued cigarette smoking, prevalent and incident cardiovascular disease, diabetes mellitus, other diseases, and higher death rates. Leanness and maintenance of stable weight were beneficial to risk factors, and to the prevention of morbidity, and death. RP HIGGINS, M (reprint author), NHLBI,DEPT EPIDEMIOL & BIOMETRY,2C08 FED BLDG,7550 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 19 TC 104 Z9 105 U1 0 U2 3 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 1993 VL 119 IS 7 BP 758 EP 763 PN 2 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA MA330 UT WOS:A1993MA33000025 PM 8363211 ER PT J AU ROSENBERG, SA ANDERSON, WF BLAESE, M HWU, P YANNELLI, JR YANG, JC TOPALIAN, SL SCHWARTZENTRUBER, DJ WEBER, JS ETTINGHAUSEN, SE PARKINSON, DN WHITE, DE AF ROSENBERG, SA ANDERSON, WF BLAESE, M HWU, P YANNELLI, JR YANG, JC TOPALIAN, SL SCHWARTZENTRUBER, DJ WEBER, JS ETTINGHAUSEN, SE PARKINSON, DN WHITE, DE TI THE DEVELOPMENT OF GENE-THERAPY FOR THE TREATMENT OF CANCER SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 113TH ANNUAL SCIENTIFIC SESSION OF THE AMERICAN-SURGICAL-ASSOC CY APR 01-03, 1993 CL BALTIMORE, MD SP AMER SURG ASSOC ID TUMOR-INFILTRATING LYMPHOCYTES; ESTABLISHED PULMONARY METASTASES; DOSE RECOMBINANT INTERLEUKIN-2; ACTIVATED KILLER CELLS; NECROSIS-FACTOR; RETROVIRAL VECTORS; ADOPTIVE IMMUNOTHERAPY; INTERFERON-GAMMA; T-CELLS; MELANOMA AB Objective The authors sought to develop new treatments for patients with cancer based on the genetic modification of immune lymphocytes and tumor cells designed to increase the host immune reaction against growing cancers. Methods Retroviral-mediated gene transduction was used to introduce genes into.tumor-infiltrating lymphocytes (TIL), and these genetically altered TIL were administered to patients with cancer. Genes coding for cytokines were introduced into tumor cells, and these cells were used to immunize patients against their autologous cancers. Results In initial studies, the gene for neomycin phosphotransferase was introduced into the TIL of ten patients with advanced cancer to study the survival and distribution of TIL in humans. These studies showed that retroviral gene transduction is a safe and practical method for adding genes to human cells and led to clinical trials in which the gene for tumor necrosis factor (TNF) was inserted into TIL in an effort to increase their therapeutic effectiveness. Phase I trials are currently underway using TIL that secrete up to 1 00 times the normal level of TNF. More recently, animal experiments have revealed that transduction of tumor cells with cytokine genes can enhance tumor immunogenicity and, thus, increase the recognition of the tumor as foreign by the host. Clinical trials based on these observations have begun in which patients are immunized against their own autologous tumors that were transduced with the genes for TNF or interleukin-2. Conclusions Attempts at gene therapy for cancer are underway and have opened new possibilities for the development of cancer treatments. RP ROSENBERG, SA (reprint author), NCI,SURG BRANCH,BETHESDA,MD 20892, USA. NR 35 TC 63 Z9 63 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD OCT PY 1993 VL 218 IS 4 BP 455 EP 464 DI 10.1097/00000658-199310000-00006 PG 10 WC Surgery SC Surgery GA MB500 UT WOS:A1993MB50000005 PM 8215637 ER PT J AU GREM, JL DRAKE, JC ALLEGRA, CJ AF GREM, JL DRAKE, JC ALLEGRA, CJ TI MEASUREMENT OF ASPARTATE CARBAMOYLTRANSFERASE ACTIVITY BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY SO ANTI-CANCER DRUGS LA English DT Article DE ASPARTATE CARBAMOYLTRANSFERASE; BIOCHEMICAL MONITORING; HPLC; N-(PHOSPHONACETYL)-1-ASPARTATE ID MOUSE SPLEEN; N-(PHOSPHONACETYL)-L-ASPARTATE; TRANSCARBAMYLASE; RESISTANCE; MECHANISM; CARCINOMA; ENZYMES; ACID AB We developed an assay which permits measurement of aspartate carbamoyltransferase (ACTase) activity. Cytosol from human peripheral blood mononuclear cells was used as the enzyme source. Using [C-14]carbamoyl phosphate as the radiolabeled substrate, the formation of [C-14]carbamoyl aspartate was quantitated by high performance liquid chromatography (HPLC) using an anion-exchange column with UV detection at 200-280 nm and an on-line liquid scintillation detector. A gradient method from an initially low concentration of ammonium phosphate, 1 mM (pH 3.0), to a higher concentration, 38 mM (pH 4.5), was used. The apparent K(m) values of carbamoyl phosphate and aspartate were 58 muM and 1.9 mM, respectively. ACTase inhibition by N-(phosphonacetyl)-l-aspartate (PALA) was consistent with a competitive model with respect to carbamoyl phosphate. The assay conditions were optimized to permit measurement of ACTase activity prior to and following therapy with PALA; ACTase was inhibited in a dose-dependent manner. This HPLC method permits direct quantitation of both the product of the reaction and the initial integrity of the substrate, [C-14]carbamoyl phosphate, which is unstable in aqueous solutions. RP GREM, JL (reprint author), NCI,NATL NAVAL MED CTR,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,NCI NAVY MED ONCOL PROGRAM,BLDG 8,BETHESDA,MD 20889, USA. NR 19 TC 1 Z9 1 U1 1 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD OCT PY 1993 VL 4 IS 5 BP 545 EP 554 DI 10.1097/00001813-199310000-00003 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA MD957 UT WOS:A1993MD95700003 PM 8292811 ER PT J AU QUEENER, SF BARTLETT, MS NASR, M SMITH, JW AF QUEENER, SF BARTLETT, MS NASR, M SMITH, JW TI 8-AMINOQUINOLINES EFFECTIVE AGAINST PNEUMOCYSTIS-CARINII IN-VITRO AND IN-VIVO SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CLINDAMYCIN PRIMAQUINE; RAT-LIVER; PNEUMONIA; PROPHYLAXIS; EFFICACY; METABOLITES; THERAPY; MODELS; AIDS; DRUG AB The activities of 25 8-aminoquinolines were compared in tests assessing the ability of the compounds to inhibit the growth of Pneumocystis carinii in culture. Six compounds were effective at or below 0.03 muM: CDRI 80/53, NSC19894, NSC305805, NSC305812, WR182234, and primaquine. Four others were effective at between 0.2 and 0.03 muM: NSC305835, WR225448, WR238605, and WR242511. Fourteen drugs were also tested in a standard model of P. carinii pneumonia in rats at daily doses of 2 mg/kg of body weight in drinking water. CDRI 80/53, NSC305805, NSC305835, and WR225448 were extremely effective in the animal model. The effectiveness of WR238605, WR242511, and primaquine in the rat model has been reported elsewhere (M. S. Bartlett, S. F. Queener, R. R. Tidwell, W. K. Milhouse, J. D. Berman, W. Y. Ellis, and J. W. Smith, Antimicrob. Agents Chemother. 35:277-282, 1991). The length of the alkyl chain separating the nitrogens in the substituent at position 8 of the quinoline ring was a strong determinant of anti-P. carinii activity. C1 INDIANA UNIV,SCH MED,DEPT PATHOL,INDIANAPOLIS,IN 46202. NIAID,DIV AIDS,ROCKVILLE,MD 20892. RP QUEENER, SF (reprint author), INDIANA UNIV,SCH MED,DEPT PHARMACOL & TOXICOL,635 BARNHILL DR,INDIANAPOLIS,IN 46202, USA. FU NIAID NIH HHS [N01-AI-72647, UO1-AI-25859] NR 18 TC 33 Z9 33 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 1993 VL 37 IS 10 BP 2166 EP 2172 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA MA179 UT WOS:A1993MA17900020 PM 8257140 ER PT J AU ROSNER, JL AF ROSNER, JL TI SUSCEPTIBILITIES OF OXYR REGULON MUTANTS OF ESCHERICHIA-COLI AND SALMONELLA-TYPHIMURIUM TO ISONIAZID SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Note ID OXIDATIVE STRESS; POSITIVE CONTROL; LOCUS; RESISTANCE; CLONING; GENE; K-12; KATE; IDENTIFICATION; TUBERCULOSIS AB Escherichia coli and Salmonella typhimurium are normally resistant to >500 mug of the antituberculosis drug isonicotinic acid hydrazide (isoniazid; INH) per ml. Susceptibility to INH (<50 mug/ml) has now been found for mutants that are deficient in OxyR, the oxidative stress response regulator. Two OxyR-regulated enzymes, alkyl hydroperoxide reductase and hydroperoxidase 1, were identified as playing important roles in INH resistance. OxyR regulon mutants should be useful for identifying other determinants of INH resistance in both E. coli and Mycobacterium tuberculosis and for finding new INH-like drugs. RP ROSNER, JL (reprint author), NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 25 TC 41 Z9 44 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 1993 VL 37 IS 10 BP 2251 EP 2253 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA MA179 UT WOS:A1993MA17900037 PM 8257155 ER PT J AU LARUELLE, M ABI-DARGHAM, A CASANOVA, MF TOTI, R WEINBERGER, DR KLEINMAN, JE AF LARUELLE, M ABI-DARGHAM, A CASANOVA, MF TOTI, R WEINBERGER, DR KLEINMAN, JE TI SELECTIVE ABNORMALITIES OF PREFRONTAL SEROTONERGIC RECEPTORS IN SCHIZOPHRENIA - A POSTMORTEM STUDY SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID H-3 PAROXETINE BINDING; TRITIATED IMIPRAMINE BINDING; HUMAN-BRAIN POSTMORTEM; FRONTAL-CORTEX; SUICIDE VICTIMS; AUTORADIOGRAPHIC ANALYSIS; DOPAMINE-D2 RECEPTORS; NEUROTRANSMITTER RECEPTORS; PHYSIOLOGIC DYSFUNCTION; 5-HT2 RECEPTORS AB Background: This study investigates serotonergic receptors in prefrontal cortex of patients with schizophrenia. Methods: We measured serotonin2 receptors and serotonin uptake sites in prefrontal and occipital cortex of schizophrenics, patients with chronic schizoaffective disorders, nonpsychotic suicides, and controls. Diagnoses were established according to DSM-III-R criteria from medical chart reviews. Results: In prefrontal cortex, serotonin, density was decreased in chronic psychotics dying of natural causes, as opposed to psychotics dying of suicide, controls, and nonpsychotic suicide victims. Serotonin uptake sites were decreased in prefrontal cortex of schizophrenics and nonpsychotic suicides, but not in patients with schizoaffective disorder. None of the observed differences were clearly related to antemortem pharmacological treatments. In the occipital pole, no differences were found among the groups. Conclusions: Selective prefrontal alterations of both presynaptic and postsynaptic serotonin receptor densities are present in at least some schizophrenic patients. C1 NIMH, NEUROSCI CTR ST ELIZABETHS, CLIN BRAIN DISORDERS BRANCH, WASHINGTON, DC 20032 USA. NR 55 TC 188 Z9 188 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-990X EI 1538-3636 J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD OCT PY 1993 VL 50 IS 10 BP 810 EP 818 PG 9 WC Psychiatry SC Psychiatry GA MB499 UT WOS:A1993MB49900006 PM 8215804 ER PT J AU KATZEL, LI FLEG, JL PAIDI, M RAGOOBARSINGH, N GOLDBERG, AP AF KATZEL, LI FLEG, JL PAIDI, M RAGOOBARSINGH, N GOLDBERG, AP TI APOE4 POLYMORPHISM INCREASES THE RISK FOR EXERCISE-INDUCED SILENT-MYOCARDIAL-ISCHEMIA IN OLDER MEN SO ARTERIOSCLEROSIS AND THROMBOSIS LA English DT Article DE APOE; SILENT ISCHEMIA; ATHEROSCLEROSIS; AGING; EXERCISE TREADMILL TEST ID CORONARY-ARTERY DISEASE; APOLIPOPROTEIN-E POLYMORPHISM; DENSITY LIPOPROTEIN CHOLESTEROL; GENETIC-VARIATION; HEART-DISEASE; DIETARY-FAT; E PHENOTYPE; PLASMA; PREVALENCE; OBESITY AB The apolipoprotein (apo) E4 polymorphism is associated with increased risk for symptomatic coronary artery disease (CAD). This study examines whether the apoepsilon4 allele is associated with an increased risk for exercise-induced silent myocardial ischemia (SI) in healthy, older (62 +/- 7 years; mean +/- SD), normocholesterolemic, nonsmoking male volunteers. The apoepsilon4 allele was present in 20 of 45 (44%) men with SI on graded exercise treadmill testing compared with 22 of 127 (17%) men of comparable age with normal exercise tests (P<.001), resulting in a crude relative risk of 2.57 (95% confidence limits, 1.57 to 4.23) for SI in men with the apoepsilon4 allele compared with those without the epsilon4 allele. Although the lipoprotein lipid levels did not differ between men with normal exercise tests and those with SI, the men with the apoE 4/3 phenotype had higher total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels than those with the apoE 2/3 and 313 phenotypes (P<.05). Men with SI and the apoE 4/3 phenotype were older (64 +/- 5 versus 57 +/- 8 years, P<.01) and leaner (P<.01) than the normal non-SI men with the apoE 4/3 phenotype. The older age of the men with SI and the apoE 413 phenotype is consistent with a progression of atherosclerosis over time. Men with SI and the apoE 313 phenotype were of comparable age and body composition to apoE 313 phenotype men with normal exercise tests. Thus, even in the presence of normal LDL-C levels, the apoepsilon4 allele may predispose older men to SI. C1 UNIV MARYLAND,SCH MED,DEPT MED,DIV GERONTOL,BALTIMORE,MD 21201. NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. MEDLANT RES INST,WASHINGTON,DC. RP KATZEL, LI (reprint author), BALTIMORE VET ADM MED CTR,10 N GREENE ST,BALTIMORE,MD 21201, USA. FU NIA NIH HHS [P01 AG004402-05, R01 AG07660-02, NIA 5-K08-AG00497] NR 31 TC 42 Z9 44 U1 1 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1049-8834 J9 ARTERIOSCLER THROMB JI Arterioscler. Thromb. PD OCT PY 1993 VL 13 IS 10 BP 1495 EP 1500 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MB206 UT WOS:A1993MB20600014 PM 8399087 ER PT J AU VARGA, J HEIMANPATTERSON, T MUNOZ, S LOVE, LA AF VARGA, J HEIMANPATTERSON, T MUNOZ, S LOVE, LA TI MYOPATHY WITH MITOCHONDRIAL ALTERATIONS IN PATIENTS WITH PRIMARY BILIARY-CIRRHOSIS AND ANTIMITOCHONDRIAL ANTIBODIES SO ARTHRITIS AND RHEUMATISM LA English DT Article ID DILATED CARDIOMYOPATHY; AUTO-ANTIGEN; POLYMYOSITIS; AUTOANTIBODIES; MYOCARDITIS; DISEASE; CARRIER; ACID AB Objective. To describe a syndrome of severe progressive myopathy, cardiomyopathy, and gastrointestinal dysmotility in 2 patients with asymptomatic primary biliary cirrhosis (PBC) and circulating antimitochondrial autoantibodies, and to review pertinent literature concerning this syndrome. Methods. Clinical, electrophysiologic, serologic, and pathologic studies of the 2 affected patients were conducted. Results. Skeletal muscle involvement was manifested by progressive weakness of the proximal muscles, marked diaphragmatic dysfunction with consequent hypoventilation and respiratory failure, and moderately elevated levels of muscle-associated enzymes. Serum from both patients contained antimitochondrial antibodies that reacted with components of the mitochondrial keto acid dehydrogenase enzyme complex. Results of electromyography were consistent with a myopathic process. The microscopic and ultrastructural changes in the skeletal muscles were distinct from those of typical myositis, and were notable for striking subsarcolemmal aggregation of abnormal mitochondria in the absence of significant inflammation. Conclusion. Severe skeletal muscle, cardiac, and gastrointestinal pathology with abnormalities of the muscle mitochondria develops in a subset of patients with mild PBC and antimitochondrial antibodies. The pathogenesis of this syndrome is unclear, but may be related to the presence of the antimitochondrial autoantibodies. C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT NEUROL,PHILADELPHIA,PA 19107. NIAMSD,BETHESDA,MD. RP VARGA, J (reprint author), THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT MED,BLUEMLE LIFE SCI BLDG,ROOM 509,233 S 10TH ST,PHILADELPHIA,PA 19107, USA. FU NIAMS NIH HHS [AR-01817] NR 32 TC 21 Z9 22 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 1993 VL 36 IS 10 BP 1468 EP 1475 DI 10.1002/art.1780361020 PG 8 WC Rheumatology SC Rheumatology GA MC066 UT WOS:A1993MC06600019 PM 8216406 ER PT J AU MATHERN, P GOLDMUNTZ, EA ZHA, HB DU, Y CROFFORD, LJ WILDER, RL REMMERS, EF AF MATHERN, P GOLDMUNTZ, EA ZHA, HB DU, Y CROFFORD, LJ WILDER, RL REMMERS, EF TI 4 POLYMORPHIC MARKERS ON RAT CHROMOSOME-12 FORM A SINGLE LINKAGE GROUP SO BIOCHEMICAL GENETICS LA English DT Article DE LINKAGE ANALYSIS; SERINE DEHYDRATASE; PLASMINOGEN ACTIVATOR INHIBITOR; SIMPLE SEQUENCE REPEATS; MICROSATELLITES; RAT CHROMOSOME 12 ID MAP AB Four PCR-typable polymorphic markers were mapped to rat chromosome 12 by linkage analysis of F-2 intercross progeny of Fischer (F344/N) and Lewis (LEW/N) rat strains. The markers formed a single linkage group, covering 27.7 cM, with the following order and distance between markers: plasminogen activator inhibitor (Planh)-0.0 cM-phosphoenolpyruvate carboxykinase-related sequence 2 (Pepckr2)-15.4 cM-anonymous marker (D12N155)-12.3 cM-serine dehydratase (Sdh). All markers were identified and genotyped by PCR analysis of simple sequence repeats. The gene encoding Planh was previously assigned to rat chromosome 12 which allowed us to assign the entire linkage group to this chromosome. These markers were highly polymorphic in 13 additional inbred rat strains (BUF/N, BN/SsN, WKY/N, MNR/N, LER/N, WBB1/N, WBB2/N, MR/N, LOU/MN, SHR/N, ACI/N, SR/Jr and SS/Jr). These markers should be useful tools for further genetic studies in rats. C1 NIAMSD,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD 20892. RI Crofford, Leslie/J-8010-2013 NR 14 TC 5 Z9 5 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0006-2928 J9 BIOCHEM GENET JI Biochem. Genet. PD OCT PY 1993 VL 31 IS 9-10 BP 441 EP 448 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA MM942 UT WOS:A1993MM94200007 PM 8122998 ER PT J AU ARNOLD, TP STANDAERT, ML HERNANDEZ, H WATSON, J MISCHAK, H KAZANIETZ, MG ZHAO, LM COOPER, DR FARESE, RV AF ARNOLD, TP STANDAERT, ML HERNANDEZ, H WATSON, J MISCHAK, H KAZANIETZ, MG ZHAO, LM COOPER, DR FARESE, RV TI EFFECTS OF INSULIN AND PHORBOL ESTERS ON MARCKS (MYRISTOYLATED ALANINE-RICH C-KINASE SUBSTRATE) PHOSPHORYLATION (AND OTHER PARAMETERS OF PROTEIN-KINASE-C ACTIVATION) IN RAT ADIPOCYTES, RAT SOLEUS MUSCLE AND BC3H-1 MYOCYTES SO BIOCHEMICAL JOURNAL LA English DT Article ID MAJOR SPECIFIC SUBSTRATE; GLUCOSE-TRANSPORT; INCREASES MEMBRANE; SKELETAL-MUSCLE; PHOSPHOLIPASE-C; DIACYLGLYCEROL; INVIVO; STIMULATION; DIAPHRAGM; HEPATOCYTES AB To evaluate the question of whether or not insulin activates protein kinase C (PKC), we compared the effects of insulin and phorbol esters on the phosphorylation of the PKC substrate, i.e. myristoylated alanine-rich C-kinase substrate (MARCKS). In rat adipocytes, rat soleus muscle and BC3H-1 myocytes, maximally effective concentrations of insulin and phorbol esters provoked comparable, rapid, 2-fold (on average), non-additive increases in the phosphorylation of immunoprecipitable MARCKS. These effects of insulin and phorbol esters on MARCKS phosphorylation in intact adipocytes and soleus muscles were paralleled by similar increases in the phosphorylation of an exogenous, soluble, 85 kDa PKC substrate (apparently a MARCKS protein) during incubation of post-nuclear membrane fractions in vitro. Increases in the phosphorylation of this 85 kDa PKC substrate in vitro were also observed in assays of both plasma membranes and microsomes obtained from rat adipocytes that had been treated with insulin or phorbol esters. These insulin-induced increases in PKC-dependent phosphorylating activities of adipocyte plasma membrane and microsomes were associated with increases in membrane contents of diacylglycerol, PKC-beta1 and PKC-beta2. Our findings suggest that insulin both translocates and activates PKC in rat adipocytes, rat soleus muscles and BC3H-1 myocytes. C1 NCI,GENET & CARCINOGENESIS LABS,BETHESDA,MD 20892. UNIV S FLORIDA,JAMES A HALEY VET HOSP,DEPT INTERNAL MED,TAMPA,FL 33612. UNIV S FLORIDA,JAMES A HALEY VET HOSP,DEPT BIOCHEM & MOLEC BIOL,TAMPA,FL 33612. RI Mischak, Harald/E-8685-2011; Farese, Robert/B-3605-2015 FU NIDDK NIH HHS [DK38079] NR 42 TC 35 Z9 35 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD OCT 1 PY 1993 VL 295 BP 155 EP 164 PN 1 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MA996 UT WOS:A1993MA99600022 PM 8216211 ER PT J AU VITIELLO, B VEITH, RC MOLCHAN, SE MARTINEZ, RA LAWLOR, BA RADCLIFFE, J HILL, JL SUNDERLAND, T AF VITIELLO, B VEITH, RC MOLCHAN, SE MARTINEZ, RA LAWLOR, BA RADCLIFFE, J HILL, JL SUNDERLAND, T TI AUTONOMIC DYSFUNCTION IN PATIENTS WITH DEMENTIA OF THE ALZHEIMER-TYPE SO BIOLOGICAL PSYCHIATRY LA English DT Article DE ALZHEIMERS; EPINEPHRINE; NOREPINEPHRINE ID SENILE DEMENTIA; DISEASE; PLASMA; DEPRESSION; NOREPINEPHRINE; NEURONS; SCALE AB Abnormalities of the noradrenergic system have been documented in the central nervous system of patients with dementia of the Alzheimer's type (DAT). To evaluate the autonomic sympathetic system in DAT, we measured lying and standing blood pressure (BP), pulse, and plasma epinephrine (E) and norepinephrine (NE) in 60 DAT patients (mean age +/- SD = 65 +/- 8 years), and 20 normal elderly controls. DAT patients had normal baseline findings (BP, pulse, NE, and E). Upon standing, plasma NE and E significantly increased in both DAT patients and controls, without group differences. However, the systolic BP response to standing was reduced in DAT patients compared with the normal controls (repeated measures ANOVA, p < 0.01). This impaired response of the systolic BP on standing was particularly evident in DAT patients with symptoms of depression. Severely impaired DAT patients did not differ in E, NE, BP, pulse, or in orthostatic changes from mild-to-moderately impaired patients. These results suggest that the sympathetic response to the stress of standing is functionally impaired in DAT. This deficit was especially evident when DAT was accompanied by depression, consistent with prior studies in non-demented depressed patients. C1 UNIV WASHINGTON,SCH MED,DEPT PSYCHIAT & BEHAV SCI,SEATTLE,WA 98195. VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,SEATTLE,WA 98108. RP VITIELLO, B (reprint author), NIMH,CLIN SCI LAB,GERIATR PSYCHIAT SECT,NIH CLIN CTR,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 22 TC 44 Z9 44 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 1993 VL 34 IS 7 BP 428 EP 433 DI 10.1016/0006-3223(93)90233-4 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA MC092 UT WOS:A1993MC09200002 PM 8268327 ER PT J AU BREIER, A KIRKPATRICK, B BUCHANAN, RW AF BREIER, A KIRKPATRICK, B BUCHANAN, RW TI CLOZAPINE ATTENUATES META-CHLOROPHENYLPIPERAZINE (MCPP)-INDUCED PLASMA-CORTISOL INCREASES IN SCHIZOPHRENIA SO BIOLOGICAL PSYCHIATRY LA English DT Note DE M-CHLOROPHENYLPIPERAZINE; SCHIZOPHRENIA; CLOZAPINE; NEUROLEPTICS; CORTISOL ID RECEPTORS; BRAIN C1 UNIV MARYLAND,SCH MED,MARYLAND PSYCHIAT RES CTR,DEPT PSYCHIAT,BALTIMORE,MD 21201. RP BREIER, A (reprint author), NIMH,EXPTL THERAPEUT BRANCH,BLDG 10,ROOM 4N214,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NIMH NIH HHS [NIMH MH40279, NIMH MH45074] NR 14 TC 23 Z9 23 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 1 PY 1993 VL 34 IS 7 BP 492 EP 494 DI 10.1016/0006-3223(93)90241-5 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA MC092 UT WOS:A1993MC09200010 PM 8268334 ER PT J AU SHARMA, R MARQUEZ, VE MILNE, GWA LEWIN, NE BLUMBERG, PM AF SHARMA, R MARQUEZ, VE MILNE, GWA LEWIN, NE BLUMBERG, PM TI CONFORMATIONALLY CONSTRAINED ANALOGS OF DIACYLGLYCEROL .5. 2,5-DIDEOXY-3-O-TETRADECANOYL-D-GALACTONO-1,4-LACTONE - A SUPERIOR HOMOLOG OF 3-O-TETRADECANOYL-2-DEOXY-L-RIBONOLACTONE WITH PK-C BINDING-AFFINITY SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID PROTEIN-KINASE-C; ACTIVATION AB A computer-generated molecular superposition of the key pharmacophores in 3-O-tetradecanoyl-2-deoxy-L-ribonolactone (1) and phorbol-12-myristate-13-acetate (PMA) indicated that the corresponding one carbon homologue, 2,5-dideoxy-3-O-tetradecanoyl-D-galactono-1,4-lactone (2) would have an improved fit to PMA. Compound 2 was synthesized, and, consistent with the model's prediction, demonstrated superior binding affinity for PK-C relative to 1. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 10 TC 5 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD OCT PY 1993 VL 3 IS 10 BP 1993 EP 1998 DI 10.1016/S0960-894X(01)81002-7 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA MH050 UT WOS:A1993MH05000017 ER PT J AU JIN, AJ NOSSAL, R AF JIN, AJ NOSSAL, R TI TOPOLOGICAL MECHANISMS INVOLVED IN THE FORMATION OF CLATHRIN-COATED VESICLES SO BIOPHYSICAL JOURNAL LA English DT Article ID RECEPTOR-MEDIATED ENDOCYTOSIS; PLASMA-MEMBRANES; PIT FORMATION; VISUALIZATION; CELLS AB By examining the basic characteristics of clathrin lattices, we discover that simple topological rules impose strict constraints on clathrin lattice transformations. These constraints require that internal bond rearrangements take place in conjunction with the addition or removal of pairs of clathrin triskelions within the interior of existing clathrin lattice patches. Similar constraints also are relevant to coated-vesicle shape changes and their budding-off from pit lattices. Via specific illustrations, successive vesicles with hexagonal-barrel and other coats are shown to grow out from the interior of a initially flat clathrin-coated pit so long as free triskelions are available from cytoplasm. Concomitantly, we present mathematical derivations of several simple and useful topological equations. These equations govern the numbers of nonhexagonal clathrin lattice facets and their variations during internal shape transformations and justify the proposed mechanisms of triskelion pair insertion and removal. RP JIN, AJ (reprint author), NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892, USA. OI Jin, Albert/0000-0003-3826-1081 NR 34 TC 35 Z9 35 U1 0 U2 2 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 1993 VL 65 IS 4 BP 1523 EP 1537 PG 15 WC Biophysics SC Biophysics GA MC124 UT WOS:A1993MC12400022 PM 8274646 ER PT J AU JAIN, VK GUPTA, A MAGRATH, IT AF JAIN, VK GUPTA, A MAGRATH, IT TI A RAPID SCREENING METHOD FOR BACTERIA CONTAINING FIREFLY LUCIFERASE PLASMIDS SO BIOTECHNIQUES LA English DT Note C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NR 3 TC 2 Z9 2 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 1993 VL 15 IS 4 BP 600 EP 602 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MB413 UT WOS:A1993MB41300008 PM 8251159 ER PT J AU ELLISON, J DEAN, M GOLDMAN, D AF ELLISON, J DEAN, M GOLDMAN, D TI EFFICACY OF FLUORESCENCE-BASED PCR-SSCP FOR DETECTION OF POINT MUTATIONS SO BIOTECHNIQUES LA English DT Article ID POLYMERASE CHAIN-REACTION; DNA; POLYMORPHISMS AB We assessed the efficiency of fluorescence-based PCR single-strand conformation polymorphism analysis (PCR-SSCP) using an automated DNA sequencer and analysis software. We evaluated 48 point mutations in a 191-bp stretch of mouse beta-globin. The mutations included 10 transversions and 38 transitions; and both types of mutation were compared at six different locations in the PCR fragment. Mobilities of the red dye-labeled internal standard fragments were non-proportional to size but highly reproducible and were used to normalize or correct minor differences in apparent electrophoretic mobility between lanes. Forty-six of forty-eight mutants (96%) were distinguished from wild type when run in separate lanes using one, set of conditions. Co-electrophoresis of wild type and mutant in the same lane resolved 100% of 45 mutants from wild type. Under conditions of this study, the magnitude of mobility shifts resulting from the globin mutations were largely determined by position of the mutation, rather than by the nature of the substitution (transition vs. transversion). However, examination of paired mutations at the same position revealed that some substitutions cause greater mobility shifts than others. C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. RP ELLISON, J (reprint author), NIAAA,NEUROGENET LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. 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 11 TC 45 Z9 45 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 1993 VL 15 IS 4 BP 684 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MB413 UT WOS:A1993MB41300025 PM 8251171 ER PT J AU WATKINS, BA DAVIS, AE COCCHI, F REITZ, MS AF WATKINS, BA DAVIS, AE COCCHI, F REITZ, MS TI A RAPID METHOD FOR SITE-SPECIFIC MUTAGENESIS USING LARGER PLASMIDS AS TEMPLATES SO BIOTECHNIQUES LA English DT Article ID POLYMERASE CHAIN-REACTION; DIRECTED MUTAGENESIS; RECOMBINATION; PCR; PRIMERS; DNA AB To facilitate the introduction of specific point mutations in plasmids that are too large to be amplified efficiently by a single PCR, we have developed a method for site-directed mutagenesis by generating partial plasmid fragments, which introduces changes as simply as conventional techniques. Plasmids containing a fragment of the human immunodeficiency virus type-1 (HIV-1) envelope gene were subjected to PCR with four pairs of PCR primers for each desired point mutation. One primer in each of two of these four pairs contained the desired mutation. The four pairs of primers were designed so that four overlapping fragments were amplified from the plasmid template, two of which contained the mutation. These fragments were then reannealed and electroporated directly into Escherichia coli. The desired mutation was typically found in 66% to 83% of the resulting colonies. The technique is almost as simple as previous techniques, shows similar efficiency and is applicable to plasmids that would normally be too large for efficient site-specifc mutagenesis. The entire procedure, from PCR amplification to transfection into E. coli, can be completed in one day. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NR 15 TC 12 Z9 12 U1 0 U2 2 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD OCT PY 1993 VL 15 IS 4 BP 700 EP 704 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MB413 UT WOS:A1993MB41300027 PM 8251172 ER PT J AU BODINE, DM MORITZ, T DONAHUE, RE LUSKEY, BD KESSLER, SW MARTIN, DIK ORKIN, SH NIENHUIS, AW WILLIAMS, DA AF BODINE, DM MORITZ, T DONAHUE, RE LUSKEY, BD KESSLER, SW MARTIN, DIK ORKIN, SH NIENHUIS, AW WILLIAMS, DA TI LONG-TERM IN-VIVO EXPRESSION OF A MURINE ADENOSINE-DEAMINASE GENE IN RHESUS-MONKEY HEMATOPOIETIC-CELLS OF MULTIPLE LINEAGES AFTER RETROVIRAL-MEDIATED GENE-TRANSFER INTO CD34+ BONE-MARROW CELLS SO BLOOD LA English DT Note ID STEM-CELLS; DEFICIENCY; CULTURE; TRANSPLANTATION; THERAPY; MICE; VECTORS; SAFE C1 INDIANA UNIV,SCH MED,HOWARD HUGHES MED INST,HERMAN B WELLS CTR PEDIAT RES,INDIANAPOLIS,IN 46202. USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20814. HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. RP BODINE, DM (reprint author), NHLBI,CLIN HEMATOL BRANCH,NIH BLDG 10,ROOM 7C103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [5 RO1-HL46528-03] NR 34 TC 191 Z9 191 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 1 PY 1993 VL 82 IS 7 BP 1975 EP 1980 PG 6 WC Hematology SC Hematology GA MA663 UT WOS:A1993MA66300006 PM 7691243 ER PT J AU SANDER, CA YANO, T CLARK, HM HARRIS, C LONGO, DL JAFFE, ES RAFFELD, M AF SANDER, CA YANO, T CLARK, HM HARRIS, C LONGO, DL JAFFE, ES RAFFELD, M TI P53 MUTATION IS ASSOCIATED WITH PROGRESSION IN FOLLICULAR LYMPHOMAS SO BLOOD LA English DT Note ID NON-HODGKINS LYMPHOMA; TUMOR SUPPRESSOR GENE; CHRONIC LYMPHOCYTIC-LEUKEMIA; POLYMERASE CHAIN-REACTION; CELL-CYCLE CHECKPOINT; C-MYC ONCOGENE; MALIGNANT-LYMPHOMAS; LUNG-CANCER; HISTOLOGIC PROGRESSION; CLINICAL-FEATURES C1 NCI,PATHOL LAB,HEMATOPATHOL SECT,BLDG 10,ROOM 2N110,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,BETHESDA,MD 20892. NR 55 TC 326 Z9 327 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 1 PY 1993 VL 82 IS 7 BP 1994 EP 2004 PG 11 WC Hematology SC Hematology GA MA663 UT WOS:A1993MA66300010 PM 8400252 ER PT J AU FIBACH, E PRASANNA, P RODGERS, GP SAMID, D AF FIBACH, E PRASANNA, P RODGERS, GP SAMID, D TI ENHANCED FETAL HEMOGLOBIN PRODUCTION BY PHENYLACETATE AND 4-PHENYLBUTYRATE IN ERYTHROID PRECURSORS DERIVED FROM NORMAL DONORS AND PATIENTS WITH SICKLE-CELL-ANEMIA AND BETA-THALASSEMIA SO BLOOD LA English DT Article ID WASTE NITROGEN-EXCRETION; GAMMA-GLOBIN SYNTHESIS; LIQUID CULTURE; DIFFERENTIATION; HYDROXYUREA; PROGENITORS; INDUCTION; DISEASE; ACID; UREA C1 NCI,CLIN PHARMACOL BRANCH,BLDG 10,ROOM 12C103,BETHESDA,MD 20892. HADASSAH UNIV HOSP,DEPT HEMATOL,JERUSALEM,ISRAEL. NIDDKD,CHEM BIOL LAB,BETHESDA,MD. NR 40 TC 106 Z9 106 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 1 PY 1993 VL 82 IS 7 BP 2203 EP 2209 PG 7 WC Hematology SC Hematology GA MA663 UT WOS:A1993MA66300038 PM 7691251 ER PT J AU LENZ, FA SEIKE, M LIN, YC BAKER, FH ROWLAND, LH GRACELY, RH RICHARDSON, RT AF LENZ, FA SEIKE, M LIN, YC BAKER, FH ROWLAND, LH GRACELY, RH RICHARDSON, RT TI NEURONS IN THE AREA OF HUMAN THALAMIC NUCLEUS VENTRALIS CAUDALIS RESPOND TO PAINFUL HEAT STIMULI SO BRAIN RESEARCH LA English DT Article DE PAIN; HUMAN THALAMUS; VENTRAL POSTERIOR NUCLEUS; MICROSTIMULATION; WIDE DYNAMIC RANGE CELL; HIGH THRESHOLD CELL; SINGLE NEURON ANALYSIS; THERMORECEPTION ID SINGLE-UNIT ANALYSIS; PRIMATE SPINOTHALAMIC PATHWAYS; POSTERIOR LATERAL NUCLEUS; CENTRAL NERVOUS-SYSTEM; SOMATOSENSORY RESPONSES; AWAKE MONKEY; CELLS; TRACT; CAT; TERMINATIONS AB A population of neurons in the area of human thalamic nucleus ventralis caudalis (Vc) respond to noxious heat stimuli. In the cutaneous co,e of Vc 6% (6/108) of recorded neurons had a significantly greater response to noxious heat stimuli than to innocuous control stimuli. Half of these neurons (n = 3) also responded to innocuous cold stimuli. Within the region posterior and inferior to the' cutaneous core of Vc 5% (4/77) of neurons responded exclusively to noxious heat stimuli. Cells responding to noxious heat were recorded at a greater proportion (66%) of sites where painful sensations were evoked by microstimulation than at sites where nonpainful sensations were evoked (1.5%). The results suggest that neurons in the region of human Vc mediate the sensory aspect of pain. C1 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. FU NINDS NIH HHS [NS28598, K08-NS1384] NR 50 TC 84 Z9 84 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 1 PY 1993 VL 623 IS 2 BP 235 EP 240 DI 10.1016/0006-8993(93)91433-S PG 6 WC Neurosciences SC Neurosciences & Neurology GA LY947 UT WOS:A1993LY94700009 PM 8221105 ER PT J AU PATEL, D MULCAHY, D CURZEN, N SULLIVAN, A CUNNINGHAM, D SPARROW, J WRIGHT, C QUYYUMI, A FOX, K AF PATEL, D MULCAHY, D CURZEN, N SULLIVAN, A CUNNINGHAM, D SPARROW, J WRIGHT, C QUYYUMI, A FOX, K TI PROGNOSTIC-SIGNIFICANCE OF TRANSIENT ST SEGMENT CHANGES AFTER CORONARY-ARTERY BYPASS-SURGERY - A LONG-TERM (4-10-YEAR) FOLLOW-UP-STUDY SO BRITISH HEART JOURNAL LA English DT Article ID TOTAL ISCHEMIC BURDEN; SILENT MYOCARDIAL ISCHEMIA; STABLE ANGINA-PECTORIS; UNSTABLE ANGINA; CARDIAC EVENTS; DAILY LIFE; DISEASE; REVASCULARIZATION; INFARCTION; FREQUENCY AB Objective-To assess the long-term (four to 10 years) prognostic significance of transient ST segment changes on ambulatory ST segment monitoring after coronary artery bypass grafting (CABG). Patients and methods-76 patients (67 men, nine women) underwent CABG between 1982 and 1984 (n = 31) and between 1987 and 1988 (n = 45) and at a mean age of 57. All underwent 48 hours of ambulatory ST segment monitoring at a mean of 19 weeks after surgery. The results were available for assessment. All general practitioners were contacted and patients' notes reviewed. Patients were contacted by telephone. Details were recorded of intervening events (acute myocardial infarction, unstable angina, need for further revascularisation, and deaths). Event free survival curves were produced for those with and without transient ST segment changes during routine postoperative ambulatory ST segment monitoring. Results-During 3213 hours of monitoring after CABG, 21 (27.6%) of 76 patients had transient ST segment changes, of which 70% were silent. Over a mean 70 month follow up period, patients with such ischaemic changes were no more likely to have either an objective (myocardial infarction or cardiac death) or subjective (unstable angina or another revascularisation) event than those patients without ischaemic changes. This finding was the same in patients operated on between 1987 and 1988 and between 1982 and 1984. Conclusions-Although ambulatory ST segment monitoring is becoming increasingly popular in some countries as a routine investigation for ischaemia in various coronary subgroups, the findings of such an investigation, when performed after CABG, do not help to identify a subgroup more likely to have an adverse outcome during up to 10 years of follow up. There seems to be no reason to perform this investigation after surgery, and particularly to refer patients for reinvestigation because of the detection of predominantly silent ST segment changes of uncertain relevance. C1 ROYAL BROMPTON NATL HEART & LUNG HOSP,DEPT NONINVAS CARDIOL,SYDNEY ST,LONDON SW3,ENGLAND. NIH,DEPT HLTH & HUMAN SERV,BETHESDA,MD 20892. NR 23 TC 13 Z9 13 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0007-0769 J9 BRIT HEART J JI Br. Heart J. PD OCT PY 1993 VL 70 IS 4 BP 337 EP 341 PG 5 WC Cardiac & Cardiovascular Systems; History & Philosophy Of Science SC Cardiovascular System & Cardiology; History & Philosophy of Science GA MA929 UT WOS:A1993MA92900006 PM 8217441 ER PT J AU MOSCOW, JA SWANSON, CA COWAN, KH AF MOSCOW, JA SWANSON, CA COWAN, KH TI DECREASED MELPHALAN ACCUMULATION IN A HUMAN BREAST-CANCER CELL-LINE SELECTED FOR RESISTANCE TO MELPHALAN SO BRITISH JOURNAL OF CANCER LA English DT Article ID L-PHENYLALANINE MUSTARD; AMINO-ACID-TRANSPORT; MEDIATED GLUTATHIONE DEPLETION; S-TRANSFERASE ACTIVITY; BUTHIONINE SULFOXIMINE; HUMAN MEDULLOBLASTOMA; ALKYLATING-AGENTS; DRUG-RESISTANCE; CYTO-TOXICITY; TUMOR-CELLS AB An in vitro model of acquired melphalan resistance was developed by serial incubation of an MCF-7 human breast cancer cell line in increasing concentrations of melphalan. The resulting derivative cell line, Me1R MCF-7, was 30-fold resistant to melphalan. Uptake studies demonstrated decreased initial melphalan accumulation in Me1R MCF-7 cells. Inverse-reciprocal plots of initial melphalan uptake revealed a 4-fold decrease in the apparent Vmax of Me1R MCF-7 compared with WT MCF-7 (516 amol cell-1 min-1 vs 21 10 amol cell-1 min-1 respectively) as well as a decrease in the apparent Kt (36 mum vs 70 mum respectively). Two amino acid transporters have previously been identified as melphalan transporters: system L, which is sodium-independent and inhibited by 2-amino-bicyclo[2,2,1]heptane-2-carboxylic acid (BCH), and system ASC which is sodium dependent and unaffected by BCH. At low concentrations of melphalan (3-30 muM), 1 mM BCH competition eliminated the differences between the two cell lines, thus implicating an alteration of the system L transporter in the transport defect in the resistant cells. Me1R MCF-7 cells were also evaluated for glutathione-mediated detoxification mechanisms associated with melphalan resistance. There was no difference between Me1R MCF-7 and WT MCF-7 in glutathione content, glutathione-S-transferase activity and expression of pi class glutathione S-transferase RNA. In addition, buthionine sulfoximine did not reverse melphalan resistance in Me1R MCF-7 cells. Therefore, Me1R MCF-7 cells provide an in vitro model of transport-mediated melphalan resistance in human breast cancer cells. RP MOSCOW, JA (reprint author), NCI,MED BRANCH,MED BREAST CANC SECT,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 38 TC 31 Z9 31 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD OCT PY 1993 VL 68 IS 4 BP 732 EP 737 DI 10.1038/bjc.1993.419 PG 6 WC Oncology SC Oncology GA MA922 UT WOS:A1993MA92200018 PM 8398701 ER PT J AU BERNSTEIN, EF RESNIK, KS LOOSE, JH HALCIN, C KAUH, YC AF BERNSTEIN, EF RESNIK, KS LOOSE, JH HALCIN, C KAUH, YC TI SOLITARY CONGENITAL SELF-HEALING RETICULOHISTIOCYTOSIS SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID HASHIMOTO-PRITZKER TYPE; JUVENILE XANTHOGRANULOMA; HISTIOCYTOSIS-X; HAMARTOMA AB Congenital self-healing reticulohistiocytosis (CSHR) was first described in 1973 by Hashimoto and Pritzker. Since then, both multiple and solitary forms have been described. We report a further case of solitary congenital self-healing reticulohistiocytosis. CSHR is a rare disorder which frequently presents a diagnostic dilemma in the newborn. Nodular forms of systemic Langerhans cell histiocytosis may present in a manner similar to CSHR. Because their differentiation on histopathological grounds is impossible, physical examination, laboratory investigations, and follow-up are necessary to ensure a lack of systemic involvement. Although previously thought to represent a rare variant of CSHR, solitary lesions of CSHR account for almost 25% of reported cases. A review of the literature relating to solitary CSHR, and a consideration of the differential diagnosis of a solitary congenital nodule, are also presented. C1 NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. HAHNEMANN UNIV,DIV DERMATOL,PHILADELPHIA,PA 19102. HAHNEMANN UNIV,DEPT PATHOL,PHILADELPHIA,PA 19102. RP BERNSTEIN, EF (reprint author), THOMAS JEFFERSON UNIV,DEPT DERMATOL,233 S 10TH ST,SUITE 450,PHILADELPHIA,PA 19107, USA. NR 58 TC 25 Z9 26 U1 2 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD OCT PY 1993 VL 129 IS 4 BP 449 EP 454 DI 10.1111/j.1365-2133.1993.tb03175.x PG 6 WC Dermatology SC Dermatology GA MA830 UT WOS:A1993MA83000017 PM 8217762 ER PT J AU LIU, JM AUERBACH, AD ANDERSON, SM GREEN, SW YOUNG, NS AF LIU, JM AUERBACH, AD ANDERSON, SM GREEN, SW YOUNG, NS TI A TRIAL OF RECOMBINANT HUMAN SUPEROXIDE-DISMUTASE IN PATIENTS WITH FANCONI-ANEMIA SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Note ID ANEMIA; OXYGEN; LEUKOCYTES; CELLS AB Fanconi anaemia (FA) is a rare genetic disorder that predisposes to the development of aplastic anaemia and neoplasia. The pathophysiologic hallmark of FA is increased susceptibility to chromosomal breakage. Superoxide metabolism has also been shown to be involved in the cellular pathophysiology of FA. Human SOD (rh-SOD), an enzyme which dismutates superoxide, has recently been cloned and expressed in yeast. We treated four FA patients with a 2-week infusion of rh-SOD (25 mg/kg d daily) to determine whether rh-SOD had any effect on haemopoietic progenitor cell growth or on the abnormal cellular phenotype. We found that lymphocyte chromosomal aberrations induced by diepoxybutane were decreased during rh-SOD treatment in two patients and that bone marrow progenitors were increased in one patient. C1 ROCKEFELLER UNIV,INVEST DERMATOL LAB,NEW YORK,NY 10021. RP LIU, JM (reprint author), NHLBI,HEMATOL BRANCH,BLDG 10,RM 7C103,BETHESDA,MD 20892, USA. NR 12 TC 5 Z9 5 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 1993 VL 85 IS 2 BP 406 EP 408 DI 10.1111/j.1365-2141.1993.tb03186.x PG 3 WC Hematology SC Hematology GA MB411 UT WOS:A1993MB41100025 PM 8280614 ER PT J AU CAUGHEY, B AF CAUGHEY, B TI SCRAPIE-ASSOCIATED PRP ACCUMULATION AND ITS PREVENTION - INSIGHTS FROM CELL-CULTURE SO BRITISH MEDICAL BULLETIN LA English DT Article ID NEURO-BLASTOMA CELLS; PRION PROTEIN-BIOSYNTHESIS; CREUTZFELDT-JAKOB DISEASE; INFECTED PC12 CELLS; INCUBATION PERIOD; SULFATED GLYCOSAMINOGLYCANS; NEUROBLASTOMA-CELLS; DEXTRAN SULFATE; AMYLOID PLAQUES; CONGO RED AB Transmissible spongiform encephalopathies (TSEs), Alzheimer's disease and other amyloidoses result in the accumulation of abnormally stable, potentially amyloidogenic proteins that appear to play central roles in disease pathogenesis. Scrapie-infected tissue culture cells have become well-developed models for studying how the TSE-specific protein, protease-resistant PrP, is made from its apparently normal precursor. The conversion of PrP to the protease-resistant state occurs on the plasma membrane or along an endocytic pathway to the lysosomes. The protease-resistant PrP has a much longer half-life than normal PrP and its accumulation in lysosomes may feature in TSE pathogenesis. Congo red and certain sulfated glycans potently inhibit protease-resistant PrP formation or stabilization in cell culture. These and other observations suggest that an interaction of PrP with glycosaminoglycans is critical in protease-resistant PrP accumulation and raises the possibility that therapeutic strategies for TSEs and other amyloidoses could be based on blocking (pre)amyloid-glycosaminoglycan interactions. RP CAUGHEY, B (reprint author), NIAID,PERSISTENT VIRAL DIS LAB,ROCKY MT LABS,HAMILTON,MT 59840, USA. NR 57 TC 45 Z9 46 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0007-1420 J9 BRIT MED BULL JI Br. Med. Bull. PD OCT PY 1993 VL 49 IS 4 BP 860 EP 872 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA MQ917 UT WOS:A1993MQ91700009 PM 8137133 ER PT J AU GUADAGNI, F ROSELLI, M COSIMELLI, M MANNELLA, E TEDESCO, M CAVALIERE, F GRASSI, A ABBOLITO, MR GREINER, JW SCHLOM, J AF GUADAGNI, F ROSELLI, M COSIMELLI, M MANNELLA, E TEDESCO, M CAVALIERE, F GRASSI, A ABBOLITO, MR GREINER, JW SCHLOM, J TI TAG-72 (CA 72-4 ASSAY) AS A COMPLEMENTARY SERUM TUMOR-ANTIGEN TO CARCINOEMBRYONIC ANTIGEN IN MONITORING PATIENTS WITH COLORECTAL-CANCER SO CANCER LA English DT Article DE CARCINOEMBRYONIC ANTIGEN; TAG-72; CA 72-4; SERUM TUMOR MARKERS; COLORECTAL CANCER ID MONOCLONAL-ANTIBODY B72.3; CARCINOMA; CEA; CA-19-9; ADENOCARCINOMA; REACTIVITY; MARKER; COLON AB Background. Serum carcinoembryonic antigen (CEA) is the most frequently chosen tumor marker in the clinical diagnosis of colorectal carcinoma and in the long-term monitoring of patients after tumor resection. In recent years, monoclonal antibody technology has identified several new markers of neoplasia, two of which, TAG-72 and CA 19-9, are found in the sera of patients with adenocarcinoma. Serum CEA, TAG-72, and CA 19-9 were evaluated in 300 patients with either malignant (n = 200) or benign (n = 100) colorectal disease. Methods. Serum CEA, TAG-72 (CA 72-4), and CA 19-9 antigen levels were determined with a double-determinant radioimmunometric assay kit. Samples and appropriate standards were assayed in duplicate. The cutoff limits used for each assay were indicated by the manufacturer. All of the results of the CA 72-4, CEA, and CA 19-9 serum assays were separated from the clinical information until the study was completed. Results. Of the 200 patients with colorectal carcinoma, the percentage of patients whose serum samples were positive for CEA, TAG-72, or CA 19-9 was 43%, 43%, and 27%, respectively. The measurement of TAG-72 with CEA for patients with primary or recurrent colorectal carcinoma increased substantially (to 60%) the percentage of positive serum samples when compared with measuring each serum tumor marker alone. Moreover, the apparent advantage gained by measuring the two tumor markers was achieved with little increase in the number of false-positive results. Conclusions. The findings support previous observations of complementary expression of TAG-72 and CEA and indicate that a significant advantage could be gained in the detection of primary and, perhaps, recurrent colorectal carcinoma by incorporating the measurement of serum TAG-72 with that of CEA. C1 NCI,TUMOR IMMUNOL & BIOL LAB,900D ROCKVILLE PIKE,BLDG 10,ROOM 8B07,BETHESDA,MD 20892. UNIV ROMA TOR VERGATA,SCH MED,REGINA ELENA CANC INST,ROME,ITALY. UNIV ROMA TOR VERGATA,SCH MED,DEPT SURG,ROME,ITALY. REGINA ELENA INST CANC RES,DEPT SURG 1,ROME,ITALY. REGINA ELENA INST CANC RES,DEPT DIGEST ENDOSCOPY,ROME,ITALY. RI Guadagni, Fiorella/J-4432-2013; Cavaliere, Francesco/J-7635-2016 OI Guadagni, Fiorella/0000-0003-3652-0457; Cavaliere, Francesco/0000-0001-6501-8648 NR 33 TC 43 Z9 49 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 1993 VL 72 IS 7 BP 2098 EP 2106 DI 10.1002/1097-0142(19931001)72:7<2098::AID-CNCR2820720707>3.0.CO;2-G PG 9 WC Oncology SC Oncology GA LY175 UT WOS:A1993LY17500006 PM 8374868 ER PT J AU JAMISDOW, CA KLECKER, RW SAROSY, G REED, E COLLINS, JM AF JAMISDOW, CA KLECKER, RW SAROSY, G REED, E COLLINS, JM TI STEADY-STATE PLASMA-CONCENTRATIONS AND EFFECTS OF TAXOL FOR A 250-MG/M(2) DOSE IN COMBINATION WITH GRANULOCYTE-COLONY-STIMULATING FACTOR IN PATIENTS WITH OVARIAN-CANCER SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE TAXOL; HPLC; PROTEIN BINDING; PHARMACOKINETICS; OVARIAN CANCER ID PHASE-I TRIAL; INFUSION; MELANOMA; TUBULIN; AGENTS AB Taxol, a natural product initially isolated from the stem bark of the western yew Taxus brevifolia, is undergoing phase II and III evaluation due to its reported activity against a variety of tumors. Previous studies have described correlations between plasma concentrations and toxicity when taxol is given (a) at lower doses, (b) for shorter infusion times, and (c) without granulocyte-colony-stimulating factor. Because the 24-h infusion schedule is most commonly used in current clinical trials, we attempted to correlate steady-state plasma concentrations of taxol achieved with a 24-h continuous i.v. infusion with toxicities and responses. Plasma samples from 48 refractory ovarian cancer patients were obtained 1-2 h prior to the end of the first taxol infusion. Taxol concentrations were measured by high-performance liquid chromatography (HPLC). Interpatient variation of taxol plasma concentrations was small (mean +/- SD, 0.85 +/- 0.21 muM. Total taxol body clearance was 256 +/- 72 ml min-1 m-2 (mean +/- SD). Taxol plasma protein binding was 88.4% +/- 1.3% (mean +/- SD, n = 9). Grade 3-4 hematologic toxicity, mainly leukopenia, occurred in 92% of the patients. The leukopenia was transient and did not warrant a reduction in the dose of taxol. Grade 3-4 nonhematologic toxicity occurred in 8% of the patients. No severe hypersensitivity reaction or grade 3-4 neurotoxicity was observed. Correlations of plasma concentrations and toxicities were not feasible due to the high frequency of hematologic effects and the low frequency of nonhematologic toxicity. The low degree of interpatient variation in plasma concentrations hindered the development of correlations with response. C1 NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,MED BRANCH,BETHESDA,MD 20892. RP JAMISDOW, CA (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV CLIN PHARMACOL,OFF RES RESOURCES,4 RES COURT,ROOM 314,ROCKVILLE,MD 20850, USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 19 TC 72 Z9 73 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD OCT PY 1993 VL 33 IS 1 BP 48 EP 52 DI 10.1007/BF00686022 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA MC707 UT WOS:A1993MC70700008 PM 7505722 ER PT J AU SANFORD, KK PARSHAD, R PRICE, FM TARONE, RE SCHAPIRO, MB AF SANFORD, KK PARSHAD, R PRICE, FM TARONE, RE SCHAPIRO, MB TI X-RAY-INDUCED CHROMATID DAMAGE IN CELLS FROM DOWN-SYNDROME AND ALZHEIMER-DISEASE PATIENTS IN RELATION TO DNA-REPAIR AND CANCER PRONENESS SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID SINGLE-STRAND BREAKS; DOWNS-SYNDROME; SYNDROME FIBROBLASTS; LYMPHOCYTES; COMPLEMENTATION; ABERRATIONS; MECHANISMS AB Frequencies of chromatid aberrations in response to G2-phase x-irradiation were compared in PHA-stimulated blood lymphocytes from healthy control subjects, Down syndrome (DS) patients, and Alzheimer disease (AD) patients. In cells arrested with Colcemid immediately (0-30 min) after x-irradiation, DS, AD, and control cells showed similar high frequencies of chromatid breaks and gaps, representing unrepaired DNA strand breaks. Frequencies had decreased in AD and control cells arrested 30-90 min after irradiation. However, DS cells had two- to three-fold higher frequencies than AD or control cells. This result indicates deficient repair of the DNA damage in DS cells. Similar responses were obtained with lymphocytes from four of seven DS parents tested and with skin fibroblasts from DS patients compared to age-matched controls. Addition of 1-beta-D-arabinofuranosylcytosine (ara-C), an inhibitor of the repair polymerase, after x-irradiation during G2 phase increased the frequencies of chromatid breaks and gaps in lymphocytes from control and AD donors significantly more than in those from DS patients. This result indicates a deficiency in DS cells in incision at sites of x-ray-induced damage. Thus DS, like other cancer-prone genetic disorders, has a G2-phase DNA repair deficiency in strand break repair and also a second DNA repair,deficiency in incision activity. C1 NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. HOWARD UNIV,COLL MED,DEPT PATHOL,WASHINGTON,DC 20001. NIA,NEUROSCI LAB,BETHESDA,MD 20892. RP SANFORD, KK (reprint author), NCI,CELLULAR & MOLEC BIOL LAB,ROOM 2D15,BLDG 37,BETHESDA,MD 20892, USA. NR 30 TC 21 Z9 21 U1 0 U2 1 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 1993 VL 70 IS 1 BP 25 EP 30 DI 10.1016/0165-4608(93)90127-8 PG 6 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA MH185 UT WOS:A1993MH18500006 PM 8221609 ER PT J AU SHILONI, E KARP, SE CUSTER, MC SHILYANSKY, J RESTIFO, NP ROSENBERG, SA MULE, JJ AF SHILONI, E KARP, SE CUSTER, MC SHILYANSKY, J RESTIFO, NP ROSENBERG, SA MULE, JJ TI RETROVIRAL TRANSDUCTION OF INTERFERON-GAMMA CDNA INTO A NONIMMUNOGENIC MURINEFIBROSARCOMA - GENERATION OF T-CELLS IN DRAINING LYMPH-NODES CAPABLE OF TREATING ESTABLISHED PARENTAL METASTATIC TUMOR SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE DRAINING LYMPH NODES; T-CELLS; GENE MODIFICATION; IMMUNOTHERAPY; INTERFERON-GAMMA ID CLASS-II REGION; MAJOR HISTOCOMPATIBILITY ANTIGENS; MURINE TUMOR; RECOMBINANT INTERLEUKIN-2; INFILTRATING LYMPHOCYTES; PULMONARY METASTASES; GENE-TRANSFER; MHC; EXPRESSION; INVIVO AB Gene modification of tumor cells with the cDNA for interferon gamma (IFNgamma) has been shown to increase the immunogenicity of some tumor cells. In order to explore further the possible therapeutic relevance of these previous findings, two clones of the nonimmunogenic MCA-102 fibrosarcoma of C57BL/6 origin were retrovirally transduced with the cDNA encoding murine IFNgamma: 102.4JK (4JK), a clone with relatively high major histocompatibility complex (MHC) class I expression, and 102.24JK (24JK), a clone with low expression of surface MHC class I molecules. Retroviral transduction of tumor cells with the cDNA encoding for IFNgamma resulted in a substantial up-regulation of MHC class I surface expression in the 24JK clone but little change of class I in the 4JK clone. In an attempt to generate antitumor lymphocytes, these gene-modified cells were inoculated into mouse footpads and draining lymph nodes (DLN) were removed, dispersed, and cultured in vitro for 10 days with irradiated tumor cells and interleukin-2. DLN from mice bearing either unmodified tumor or tumor transduced with cDNA encoding neomycin resistance (Neo(R)) or IFNgamma, were used to treat recipients harboring 3-day pulmonary metastases induced by the parental, unmodified tumor. Treatment with DLN cells obtained following the injection of 24JK tumor cells modified with the gene for IFNgamma significantly reduced the number of pulmonary metastases in four separate experiments, compared to groups treated by DLN cells generated from inoculation of either the unmodified, parental 24JK clone or the same clone transduced with the Neo(R) gene only. In contrast, I)LN cells induced either by IFNgamma-transduced 4JK (high expression of MHC class I) or an unmodified 4JK tumor (moderate expression of MHC class I) had significant but equal therapeutic efficacy. Although the in vitro growth rate of tumor cell lines was unaffected by the insertion of the mouse IFNgamma cDNA, their in vivo (s.c.) growth rates were significantly slower than those of the nontransduced tumors. Thus, after retroviral transduction of the murine IFNgamma cDNA into a nonimmunogenic tumor with a very low level of surface expression of MHC class 1, modified tumor cells could elicit therapeutic T cells from DLN capable of successfully treating established pulmonary metastases upon adoptive transfer. This strategy significantly confirms previous observations on the potential therapeutic effects of gene modification of tumor cells with IFNgamma and extends the realm of therapeutic possibilities to include the use of DLN cells for the development of T-cell based immunotherapies against nonimmunogenic human tumors. C1 NCI,DIV CANC TREATMENT,SURG BRANCH,BLDG 10,RM 2B42,BETHESDA,MD 20892. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01] NR 40 TC 24 Z9 24 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD OCT PY 1993 VL 37 IS 5 BP 286 EP 292 DI 10.1007/BF01518450 PG 7 WC Oncology; Immunology SC Oncology; Immunology GA LZ720 UT WOS:A1993LZ72000002 PM 8402732 ER PT J AU DINI, D MACCHIA, R GOZZA, A BERTELLI, G FORNO, GG GUENZI, M BACIGALUPO, A SCOLARO, T VITALE, V AF DINI, D MACCHIA, R GOZZA, A BERTELLI, G FORNO, GG GUENZI, M BACIGALUPO, A SCOLARO, T VITALE, V TI MANAGEMENT OF ACUTE RADIODERMATITIS - PHARMACOLOGICAL OR NONPHARMACOLOGICAL REMEDIES SO CANCER NURSING LA English DT Article DE RADIOTHERAPY; SKIN CARE DURING RADIATION TREATMENT; MOIST DESQUAMATION AB The medical and nursing literature suggests a wide variety of pharmacological and nonpharmacological approaches to treatment of acute radiation skin damages (erythema, dry and moist desquamation, ulceration), but no specific and standardized therapy. The incidence of radiodermatitis has decreased with mega-voltage instruments, but it can nevertheless influence the therapeutic program and impair quality of life of patients. A study has been conducted to evaluate the tolerability and effectiveness of a nonpharmacological remedy, a mixture of hydrophobic (stearic acid) and hydrophilic (propilene glycol, glycerol, and polyunsaturated alcohols) components in a foam emulsion for the treatment of acute skin injuries following radiotherapy. Thirty-eight of 42 initial patients were evaluable: we observed a complete response in 22 (57.9%), improvement in 14 (36.8%), and failure in only two (5.3%). C1 NATL CANC INST,DEPT CANC REHABIL,GENOA,ITALY. NATL CANC INST,DEPT RADIOTHERAPY,GENOA,ITALY. NR 14 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD OCT PY 1993 VL 16 IS 5 BP 366 EP 370 PG 5 WC Oncology; Nursing SC Oncology; Nursing GA MD390 UT WOS:A1993MD39000005 PM 8261385 ER PT J AU QUINTKASNER, S LEVY, W MEADOWS, BS CARROLL, R GORRELL, CR AF QUINTKASNER, S LEVY, W MEADOWS, BS CARROLL, R GORRELL, CR TI PROGRAMMED-INSTRUCTION - CANCER-CHEMOTHERAPY - CHEMOTHERAPY AGENTS .2. SO CANCER NURSING LA English DT Article C1 NCI,BETHESDA,MD 20892. RP QUINTKASNER, S (reprint author), NIH,DEPT CLIN CTR NURSING,BETHESDA,MD 20892, USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD OCT PY 1993 VL 16 IS 5 BP 398 EP 418 PG 21 WC Oncology; Nursing SC Oncology; Nursing GA MD390 UT WOS:A1993MD39000009 PM 8261389 ER PT J AU SLAWIN, K KADMON, D PARK, SH SCARDINO, PT ANZANO, M SPORN, MB THOMPSON, TC AF SLAWIN, K KADMON, D PARK, SH SCARDINO, PT ANZANO, M SPORN, MB THOMPSON, TC TI DIETARY FENRETINIDE, A SYNTHETIC RETINOID, DECREASES THE TUMOR-INCIDENCE AND THE TUMOR MASS OF RAS+MYC-INDUCED CARCINOMAS IN THE MOUSE PROSTATE RECONSTITUTION MODEL SYSTEM SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-BETA; VITAMIN-A; MYC PROTOONCOGENE; BREAST-CANCER; RAS; ACID; EXPRESSION; N-(4-HYDROXYPHENYL)RETINAMIDE; HYPERPLASIA; ENHANCEMENT AB Several epidemiological studies have implicated low dietary and serum levels of retinol with an increased risk for the development of human prostate cancer. In a recent report, dietary fenretinide [N-[(4-hydroxyphenyl)] retinamide], a synthetic retinoid with low toxicity, decreased the incidence of experimentally induced prostate cancer. Fenretinide is currently being evaluated in phase I and phase II clinical trials as an agent for both the treatment and chemoprevention of human prostate cancer. Because of these findings, we investigated whether dietary fenretinide could alter the incidence or phenotype of oncogene-induced prostate cancer in the mouse prostate reconstitution model system. When compared to control-fed animals, dietary fenretinide reduced the tumor incidence by 49% and the tumor mass by 52% of ras+myc-induced cancers in the mouse prostate reconstitution model system, which was modified to prolong the latency period before cancer development. Retinoids have a wide ranging effect on cellular differentiation, growth factor synthesis, and immune function. While its mechanism of action in this system remains unclear, fenretinide is an effective agent for the chemoprevention and growth modulation of oncogene-induced prostate cancer in the mouse prostate reconstitution model system and may be effective for the, chemoprevention of human prostate cancer. C1 BAYLOR COLL MED,SCOTT DEPT UROL,HOUSTON,TX 77030. VET AFFAIRS MED CTR,UROL RES LAB,HOUSTON,TX. BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA50588, P50-CA58204] NR 30 TC 71 Z9 71 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 1 PY 1993 VL 53 IS 19 BP 4461 EP 4465 PG 5 WC Oncology SC Oncology GA LZ637 UT WOS:A1993LZ63700005 PM 8402613 ER PT J AU SALEH, MN KHAZAELI, MB GRIZZLE, WE WHEELER, RH LAWSON, S LIU, TP RUSSELL, C MEREDITH, R SCHLOM, J LOBUGLIO, AF AF SALEH, MN KHAZAELI, MB GRIZZLE, WE WHEELER, RH LAWSON, S LIU, TP RUSSELL, C MEREDITH, R SCHLOM, J LOBUGLIO, AF TI A PHASE-I CLINICAL-TRIAL OF MURINE MONOCLONAL-ANTIBODY D612 IN PATIENTS WITH METASTATIC GASTROINTESTINAL CANCER SO CANCER RESEARCH LA English DT Article ID COLON-CARCINOMA; IMMUNE-RESPONSE; COLORECTAL-CARCINOMA; SUPPRESSION; CELLS; PHARMACOKINETICS; FLUOROURACIL; THERAPY; B72.3 AB In a Phase I study, 21 patients with metastatic adenocarcinoma of the gastrointestinal tract received the murine monoclonal antibody D612. This antibody is directed at a M(r) 48,000 antigen restrictively expressed on tumors of the gastrointestinal tract and to a limited degree on normal gastrointestinal mucosa. Patients received total doses of 10-180 mg/m2 administered as single or multiple doses of 1-100 mg/m2 over an 8-day period. Dose-limiting toxicity was secretory diarrhea. A single dose of 100 mg/m2 exceeded guidelines for maximal tolerated dose. Higher total doses were achieved in subsequent patients by using repeated administration of lower doses. Three of five patients receiving 60 mg/m2 for 3 doses (180 mg/m2 total dose) experienced grade 3 diarrhea and could not complete the prescribed course. The dose of 40 mg/m2 administered on days 1, 4, and 8 (total dose, 120 mg/m2) has been selected as the dose for phase II studies. The pharmacokinetics of D612 is best described by a one-compartment model with a mean t1/2 of 48 +/- 3 h (SEM). Eighteen of 21 patients developed human anti-mouse antibody (HAMA). Patients who developed high levels of HAMA demonstrated a more rapid clearance of the day 8 dose than those who developed low levels of HAMA. In all patients studied, a component of HAMA was directed at the D612 variable region. With one exception, serum from all patients with detectable antibody to the D612 variable region demonstrated anti-paratope reactivity. Thirty-four % of known metastatic sites demonstrated uptake of radiolabeled D612. There were no objective antitumor responses in this phase I trial. The antitumor effect of D612 in vitro has been shown to be potentiated by interleukin 2 and recombinant human macrophage colony-stimulating factor. A phase II study of D612 administered in combination with cytokines that enhance human effector function is presently ongoing. C1 UNIV ALABAMA,CTR COMPREHENS CANC,DEPT PATHOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,CTR COMPREHENS CANC,DEPT BIOSTAT,BIRMINGHAM,AL 35294. UNIV ALABAMA,CTR COMPREHENS CANC,DEPT NUCL MED,BIRMINGHAM,AL 35294. UNIV ALABAMA,CTR COMPREHENS CANC,DEPT RADIAT ONCOL,BIRMINGHAM,AL 35294. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. RP SALEH, MN (reprint author), UNIV ALABAMA,CTR COMPREHENS CANC,DEPT MED,LB WALLACE TUMOR INST 263,BIRMINGHAM,AL 35294, USA. FU NCI NIH HHS [R-01 CA45232-05, N01 CM97611] NR 43 TC 21 Z9 21 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 1 PY 1993 VL 53 IS 19 BP 4555 EP 4562 PG 8 WC Oncology SC Oncology GA LZ637 UT WOS:A1993LZ63700022 PM 8402627 ER PT J AU WANG, QC PAI, LH DEBINSKI, W FITZGERALD, DJ PASTAN, I AF WANG, QC PAI, LH DEBINSKI, W FITZGERALD, DJ PASTAN, I TI POLYETHYLENE GLYCOL-MODIFIED CHIMERIC TOXIN COMPOSED OF TRANSFORMING GROWTH-FACTOR-ALPHA AND PSEUDOMONAS EXOTOXIN SO CANCER RESEARCH LA English DT Article ID SINGLE-CHAIN IMMUNOTOXINS; FUSION PROTEIN; RECOMBINANT INTERLEUKIN-2; COVALENT ATTACHMENT; ANTIBODY-RESPONSES; ANTITUMOR-ACTIVITY; ESCHERICHIA-COLI; FACTOR RECEPTORS; MICE; SUPPRESSION AB Modification of proteins with monomethoxy-polyethylene glycol (mPEG) has been shown to prolong circulation time and to reduce immunogenicity. To make a mPEG-modified recombinant toxin that retained cytotoxic activity but had a longer residence time in circulation, we have constructed an altered form of TGFalpha-PE40, a recombinant toxin composed of human transforming growth factor alpha (TGFalpha) fused to a fragment of Pseudomonas exotoxin (PE38) devoid of its cell- binding domain. In the newly designed protein, termed TGFalphaR29-L2-C(H)2-PE38QQDELTA (TCP), there are no lysine residues in the TGFalpha and PE38 portions. Human IgG4 constant region C(H)2 and a tetradecapeptide linker, L2, are inserted between TGFalpha and PE38. Together, L2 and C(H)2 contain 13 lysine residues as potential modification sites for mPEG. mPEG conjugates of TCP (PEG-TCP) were generated and the products were resolved by ion exchange chromatography. Two PEG-TCP species termed B4 and B6 retained 15 and 4% of cytotoxicity, respectively, and 26% of their receptor binding activity compared with the unmodified TCP. Both B4 and B6 had prolonged circulation times in the blood and reduced toxicity in animals. The mean residence times of B4 and B6 were 37 and 68 min, respectively, compared to 7 min for TCP. When administered i.v. to tumor bearing mice, both B4 and B6 produced marked antitumor effects whereas the unmodified TCP had none. Also, the immunogenicity of PEG-TCP was 5-10 times less than that of TCP. We suggest that the prolonged circulating time and reduced toxicity of PEG-TCP compensate for a diminished cytotoxic activity and enlarge significantly the therapeutic window of this chimeric toxin. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 51 TC 53 Z9 54 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 1 PY 1993 VL 53 IS 19 BP 4588 EP 4594 PG 7 WC Oncology SC Oncology GA LZ637 UT WOS:A1993LZ63700027 PM 8402632 ER PT J AU MARCHETTI, A BUTTITTA, F PELLEGRINI, S CAMPANI, D DIELLA, F CECCHETTI, D CALLAHAN, R BISTOCCHI, M AF MARCHETTI, A BUTTITTA, F PELLEGRINI, S CAMPANI, D DIELLA, F CECCHETTI, D CALLAHAN, R BISTOCCHI, M TI P53 MUTATIONS AND HISTOLOGICAL TYPE OF INVASIVE BREAST-CARCINOMA SO CANCER RESEARCH LA English DT Article ID CELLULAR TUMOR-ANTIGEN; LUNG-CANCER; MEDULLARY CARCINOMA; SUPPRESSOR GENE; EXPRESSION; TRANSFORMATION; PROTEIN; OVEREXPRESSION; PROLIFERATION; PROGNOSIS AB A polymerase chain reaction-single strand conformation polymorphism assay was used to assess p53 mutations in 148 invasive breast carcinomas, selected on the basis of their histotype. They comprised 56 lobular, 47 ductal, 19 mucinous, 18 medullary, and 8 papillary carcinomas. The distribution of p53 mutations was significantly different (P = 0.006) in the histotypes examined: mutations were frequent in medullary (39%) and ductal (26%), less common in lobular (12%), and absent in mucinous and papillary carcinomas. The frequency of mutations in the exon 5 of the p53 gene was significantly higher in medullary carcinomas than in the other histotypes: 5 (63%) of the mutations found in exon 5 were observed in medullary carcinomas (P = 0.012). One hundred twenty-two tumors from the total were also examined by immunohistochemistry for p53 overexpression using antibody PAb 1801. A specific immunostaining in neoplastic cells was present in 12 tumors. A strong correlation (P < 0.001) was observed between p53 mutations and nuclear accumulation of the p53 protein: 10 tumors were scored positive for both p53 mutation and overexpression. However, in 9 cases having a mutated p53 gene we failed to rind a positive immunoreaction. A significant association (P = 0.01) was present between mutations in the p53 gene and high proliferative activity of the tumors determined by immunohistochemistry with monoclonal antibody Ki-67. Moreover, a significantly higher expression of the Ki-67 antigen was found in medullary carcinomas compared to the other histotypes. Our findings indicate that in invasive breast carcinomas structural abnormalities of the p53 gene are mainly seen in medullary and ductal tumors and that the other histological types, especially those associated with a high level of differentiation and favorable prognosis, show a very low incidence of p53 mutations. C1 NIH,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. RP MARCHETTI, A (reprint author), UNIV PISA,INST PATHOL ANAT & HISTOL,VIA ROMA 57,I-56100 PISA,ITALY. RI Pellegrini, Silvia/C-3770-2011 NR 47 TC 105 Z9 105 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 1993 VL 53 IS 19 BP 4665 EP 4669 PG 5 WC Oncology SC Oncology GA LZ637 UT WOS:A1993LZ63700040 PM 8402644 ER PT J AU VANDENHEUVEL, JP CLARK, GC THOMPSON, CL MCCOY, Z MILLER, CR LUCIER, GW BELL, DA AF VANDENHEUVEL, JP CLARK, GC THOMPSON, CL MCCOY, Z MILLER, CR LUCIER, GW BELL, DA TI CYP1A1 MESSENGER-RNA LEVELS AS A HUMAN EXPOSURE BIOMARKER - USE OF QUANTITATIVE POLYMERASE CHAIN-REACTION TO MEASURE CYP1A1 EXPRESSION IN HUMAN PERIPHERAL-BLOOD LYMPHOCYTES SO CARCINOGENESIS LA English DT Article ID 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; TOXICITY; WORKERS; GENE AB Accurate human risk assessment requires sensitive methods to evaluate dose-response relationships, especially following low level exposures. We have developed a reverse transcriptase polymerase chain reaction (RT-PCR) method to quantitate cytochrome P450-1A1 (CYP1A1) mRNA levels in human blood lymphocytes. Many polycyclic aromatic hydrocarbons (PAH) such as benzo[a]pyrene, and chlorinated PAH such as polychlorinated dibenzodioxins, dibenzofurans and biphenyls induce CYP1A1 expression through activation of an endogenous protein, the Ah receptor. Using a quantitative competitive RT-PCR method that included a synthetic internal standard we determined copy numbers of CYP1A1 mRNA in resting as well as mitogen-stimulated human blood lymphocytes. In mitogen-stimulated human blood lympocytes assay variation was approximately 10% for measurement of this low expression gene and mRNA levels correlated well with ethoxyresorufin-O-deethylase (EROD) activity. The expression of mRNA was induced 20-fold upon culturing human lymphocytes with 10 nM TCDD. In nonstimulated, uninduced lymphocytes CYP1A1 levels are extremely low (1000 copies mRNA/10(4) celts) and cannot be measured by EROD activity. Studies of CYP1A1 mRNA expression in chemically-exposed populations are in progress. C1 NIEHS,BIOCHEM RISK ANAL LAB,C3-03,POB 12233,RES TRIANGLE PK,NC 27709. PURDUE UNIV,SCH PHARMACOL & TOXICOL,W LAFAYETTE,IN 47907. NR 21 TC 97 Z9 98 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 1993 VL 14 IS 10 BP 2003 EP 2006 PG 4 WC Oncology SC Oncology GA MD319 UT WOS:A1993MD31900003 PM 8222045 ER PT J AU DAVIS, CD SCHUT, HAJ SNYDERWINE, EG AF DAVIS, CD SCHUT, HAJ SNYDERWINE, EG TI ENZYMATIC PHASE-II ACTIVATION OF THE N-HYDROXYLAMINES OF IQ, MEIQX AND PHIP BY VARIOUS ORGANS OF MONKEYS AND RATS SO CARCINOGENESIS LA English DT Article ID FOOD-BORNE CARCINOGEN; HETEROCYCLIC AMINES; MUTAGENIC COMPOUND; COVALENT BINDING; DNA ADDUCTS; METABOLIC-ACTIVATION; COLORECTAL-CANCER; BROILED SARDINE; BEEF EXTRACT; COOKED FOODS AB 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are mutagenic and carcinogenic heterocyclic amines produced during the ordinary cooking of meat. These compounds undergo metabolic activation via both cytochrome P450-mediated N-oxidation and phase II esterification in order to exert their genotoxicity. In the current study, we examined the in vitro phase II activation of N-hydroxy-IQ, N-hydroxy-PhIP and N-hydroxy-MeIQx by cytosolic acetyltransferase, sulfotransferase, aminoacyl-tRNA synthetase and phosphatase from a number of tissues including liver, kidney, colon and heart. These tissues were chosen for study because each is either a target organ for carcinogenicity or has displayed high levels of DNA adducts in in vivo studies with the heterocyclic amines. Cytosol from various tissues of both monkeys and rats was incubated with and without the respective cofactors, and carcinogen binding to calf thymus DNA was measured by P-32-postlabeling analysis. Our results show that all four phase II enzymes may participate in the activation of the N-hydroxylamines. However, the degree of activation depends on the substrate, tissue and animal species. For example, in both monkeys and rats, the highest acetyl CoA-enhanced binding was observed with N-hydroxy-IQ and the lowest acetyl CoA-enhanced binding was observed with N-hydroxy-MeIQx. In contrast, no significant adenosine 3'-phosphate 5'-phosphosulfate-dependent activation of N-hydroxy-IQ was observed with monkey cytosol from liver, kidney, heart or colon but the sulfotransferase-mediated activation of N-hydroxy-PhIP was at least 10 times higher in all four tissues of monkeys than in rats. Prolylation appears important in the activation of all three N-hydroxylamines by rat liver and heart cytosol, whereas in monkeys, prolylation appears important in kidney cytosol. The differences observed in the phase II activation of heterocyclic amines may have implications for DNA adduct formation, toxicity and carcinogenicity. C1 MED COLL OHIO,DEPT PATHOL,TOLEDO,OH 43614. RP DAVIS, CD (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BLDG 37,ROOM 3C28,BETHESDA,MD 20892, USA. NR 39 TC 79 Z9 79 U1 1 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 1993 VL 14 IS 10 BP 2091 EP 2096 DI 10.1093/carcin/14.10.2091 PG 6 WC Oncology SC Oncology GA MD319 UT WOS:A1993MD31900017 PM 8222059 ER PT J AU PIRSEL, M BOHR, VA AF PIRSEL, M BOHR, VA TI METHYL METHANESULFONATE ADDUCT FORMATION AND REPAIR IN THE DHFR GENE AND IN MITOCHONDRIAL-DNA IN HAMSTER-CELLS SO CARCINOGENESIS LA English DT Article ID DIHYDROFOLATE-REDUCTASE GENE; OVARY CELLS; 3-METHYLADENINE-DNA GLYCOSYLASE; APURINIC SITES; NUCLEAR-DNA; CHINESE; DAMAGE; 7-METHYLGUANINE; PURIFICATION; MUTAGENESIS AB Chinese hamster ovary CHO-B11 cells were exposed to methyl methanesulfonate (MMS) and the formation and repair of N-methylpurines were measured in the endogenous dihydrofolate reductase (DHFR) gene domain and in mitochondrial DNA by alkaline hydrolysis which generates strand breaks at apurinic (AP) sites formed after neutral depurination. The initial levels of damage in the transcriptionally active DHFR gene, 3'-flanking non-transcribed region and in mitochondrial DNA were slightly different; the highest level of damage was in mitochondrial DNA, the lowest in the DHFR gene. The rate of adduct removal was similar in all three DNA regions examined. We conclude that there is no preferential repair of MMS induced N-methylpurines under these conditions, and that these lesions are efficiently removed from mitochondrial DNA. C1 SLOVAK ACAD SCI,DEPT MOLEC GENET,CANC RES INST,CS-80936 BRATISLAVA,CZECHOSLOVAKIA. NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RI Pirsel, Miroslav/A-9996-2008 NR 35 TC 30 Z9 31 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 1993 VL 14 IS 10 BP 2105 EP 2108 DI 10.1093/carcin/14.10.2105 PG 4 WC Oncology SC Oncology GA MD319 UT WOS:A1993MD31900019 PM 8222061 ER PT J AU LEE, KB PARKER, RJ BOHR, V CORNELISON, T REED, E AF LEE, KB PARKER, RJ BOHR, V CORNELISON, T REED, E TI CISPLATIN SENSITIVITY RESISTANCE IN UV REPAIR-DEFICIENT CHINESE-HAMSTER OVARY CELLS OF COMPLEMENTATION GROUP-1 AND GROUP-3 SO CARCINOGENESIS LA English DT Article ID EXCISION REPAIR; DNA-REPAIR; BIOLOGICAL CHARACTERIZATION; MOLECULAR-CLONING; GENE ERCC-1; A2780 CELLS; EXPRESSION; PLATINUM; ACID AB We assessed the possible role of the human repair genes, ERCC1 and ERCC3, in resistance to cisplatin-induced cytotoxicity. The UV repair-deficient Chinese hamster ovary (CHO) 43:3B [designated ERCC1(-), cell line and its paired subline 83-J5, which is stably transfected with the human DNA excision repair gene ERCC1 [designated ERCC1(+)], were used in this study. UV repair-deficient CHO 27-1 cells [designated ERCC3(-)] and its paired subline designated 'ERCC3(+)', which is stably transfected with the human DNA excision repair gene ERCC3, were also used. In each pair of cell lines, we assessed cisplatin cytotoxicity, cellular drug accumulation and platinum - DNA adduct repair after 1 h drug exposures. Drug accumulation and DNA repair were assessed by atomic absorption spectrometry with Zeeman background correction. ERCC1(+) cells (IC50 = 4.0 muM) were 5-fold more resistant to cisplatin than ERCC1(-) cells (IC 50 = 0.75 muM). ERCC1(+) cells repaired 25% of DNA lesions in cellular DNA within a 6 h time period following an IC50 drug exposure and repaired 48% over 24 h. No DNA repair was observed in ERCC1(-) cells during the same time periods. Both cell lines showed similar patterns of drug accumulation. For ERCC3(-) cells (IC50 = 54 muM and ERCC3(+) cells (IC50 = 49 muM), the profiles of cisplatin sensitivity and cellular drug accumulation were similar. When treated with 50 muM cisplatin, these cells showed similar patterns of drug accumulation, and were equally efficient at forming and repairing lesions in cellular DNA. These data show that in UV repair-deficient CHO cells, ERCC1 confers resistance to cisplatin and confers the ability to remove platinum from cellular DNA. In contrast, ERCC3 does not influence cisplatin drug sensitivity or adduct repair capability. This suggests that ERCC1 may be a determinant of cisplatin resistance, whereas ERCC3 is probably not. C1 NCI,MED BRANCH,MED OVARIAN CANC SECT,BLDG 10,ROOM 12N 226,BETHESDA,MD 20892. NIA,MOLEC GENET LAB,BALTIMORE,MD 21224. NR 25 TC 96 Z9 102 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 1993 VL 14 IS 10 BP 2177 EP 2180 DI 10.1093/carcin/14.10.2177 PG 4 WC Oncology SC Oncology GA MD319 UT WOS:A1993MD31900032 PM 8222071 ER PT J AU DILISA, F GAMBASSI, G SPURGEON, H HANSFORD, RG AF DILISA, F GAMBASSI, G SPURGEON, H HANSFORD, RG TI INTRAMITOCHONDRIAL FREE CALCIUM IN CARDIAC MYOCYTES IN RELATION TO DEHYDROGENASE ACTIVATION SO CARDIOVASCULAR RESEARCH LA English DT Article ID FREE CA-2+ CONCENTRATION; PYRUVATE-DEHYDROGENASE; RAT-HEART; PIG-HEART; CA2+; MITOCHONDRIA; IONS; METABOLISM; TRANSPORT; STIMULATION AB Objective: The aim was to quantitate intramitochondrial free Ca2+ ([Ca2+]m) in cardiac myocytes under conditions of stimulation previously shown to cause activation of pyruvate dehydrogenase. Methods: [Ca2+]m was monitored in single, isolated rat cardiac myocytes using fluorescence microscopy following the loading of the cells with the fluorescent chelating agent indo-1, in its permeant acetoxymethylester form, and the selective quenching of cytosolic fluorescence with MnCl2. The extent of contraction upon electrical stimulation was also measured. Results: Electrical stimulation at 2 Hz and higher frequency raised [Ca2+]m significantly, and this was potentiated by exposure to isoprenaline. However, isoprenaline had no effect in quiescent cells, in which [Ca2+]m was raised above resting values by partial replacement of Na+ in the medium. The mitochondrial uncoupling agent carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) raised [Ca2+]m in unstimulated cells, but lowered it in cells subjected to electrical stimulation at 2 Hz or more, to partial Na+ replacement, or to the alkaloid veratridine. Conclusions: The values of [Ca2+]m in quiescent myocytes (approximately 100 nmol.litre-1) would be associated with very little activation by Ca2+ of pyruvate dehydrogenase phosphatase, based on determination of K0.5 value of 650 nmol.litre-1 in work with mitochondrial suspensions. By contrast, the values of [Ca2+]m associated with electrical stimulation at 2 Hz or greater in the presence of beta adrenergic activation (>500 nmol.litre-1) would be associated with significant dehydrogenase activation. The effect of beta adrenergic activation is only seen in the presence of electrical stimulation and probably involves enhancement of systolic transients in cytosol [Ca2+]. Effects of uncoupling agents validate the conclusions on the direction and magnitude of the mitochondrial Ca2+ adient in situ in living myocytes. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224. NR 26 TC 41 Z9 41 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD OCT PY 1993 VL 27 IS 10 BP 1840 EP 1844 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA MD320 UT WOS:A1993MD32000021 PM 8275533 ER PT J AU JI, H SANDBERG, K BONNER, TI CATT, KJ AF JI, H SANDBERG, K BONNER, TI CATT, KJ TI DIFFERENTIAL ACTIVATION OF INOSITOL 1,4,5-TRISPHOSPHATE-SENSITIVE CALCIUM POOLS BY MUSCARINIC RECEPTORS IN XENOPUS-LAEVIS OOCYTES SO CELL CALCIUM LA English DT Article ID ADRENAL CHROMAFFIN CELLS; ANGIOTENSIN-II RECEPTORS; OVARIAN FOLLICLES; CYTOSOLIC CA-2+; TRISPHOSPHATE; MOBILIZATION; METABOLISM; PHOSPHATES; DISTINCT; RELEASE AB Muscarinic acetylcholine (ACh) receptors activate the phospholipase C signal transduction pathway to promote the formation of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and the consequent elevation of cytoplasmic calcium (Ca2+). The inositol phosphate and Ca2+-mobilization responses to ACh were analyzed in Xenopus oocytes possessing endogenous receptors, and in oocytes expressing exogenous receptors from injected muscarinic RNA transcripts, to evaluate the patterns of signal transduction mediated by native and expressed receptors. Activation of native ACh receptors elicited dose- and time-dependent increases in Ins(1,4,5)P3 and inositol bisphosphate (InsP2) production. ACh-induced Ins(1,4,5)P3 production increased rapidly within the first 2 min and continued to rise over the next 20 min. ACh was a much more effective stimulus of inositol phosphate production at native (up to 35-fold) than at expressed receptors (less than 2-fold). In contrast, measurements of Ca2+-mobilization in oocytes injected with the Ca2+-specific photoprotein, aequorin, revealed that ACh stimulation of expressed receptors evoked up to 200-fold increase in light emission, whereas ACh stimulation of native receptors elicited less than a 24 old response. These observations indicate that the oocyte possesses functionally distinct agonist-sensitive Ca2+ pools which differ markedly in their sensitivity to Ins(1,4,5)P3 production and suggest that these pools are mobilized by different effector mechanisms. The finding that the magnitude of the intra-oocyte Ca2+ response is not necessarily determined by the degree of Ins(1,4,5)P3 production, but rather by another aspect of the signal transduction pathway (e.g. the nature and/or location of the Ins(1,4,5)P3 releasable Ca2+ pool), reveals an additional level of complexity in the transduction mechanisms responsible for intracellular Ca2+ signaling. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,BLDG 49,RM 6A36,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NR 46 TC 8 Z9 8 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD OCT PY 1993 VL 14 IS 9 BP 649 EP 662 PG 14 WC Cell Biology SC Cell Biology GA LZ959 UT WOS:A1993LZ95900004 PM 8242720 ER PT J AU BUTTON, D BROWNSTEIN, M AF BUTTON, D BROWNSTEIN, M TI AEQUORIN-EXPRESSING MAMMALIAN-CELL LINES USED TO REPORT CA-2+ MOBILIZATION SO CELL CALCIUM LA English DT Article ID CALCIUM; CDNA; PROTEIN; APOAEQUORIN; RECEPTOR; CLONING; SYSTEM; DNA AB Mammalian cells that stably express jellyfish aequorin have been used to report activation of Ca2+ mobilization by cell-surface receptors. Expression of aequorin cDNA (pAEQ) was driven by the cytomegalovirus (CMV) promotor in CHO-K1 and 293 cells. Clonal isolates were obtained which express high levels of apo-aequorin protein, the Ca2+-dependent luminescence of which is generated by treatment of living cells with the coelenterate luciferin, coelenterazine. Transient expression of aequorin in COS cells results in even greater abundance of luminescent protein. Aequorin protein is lost from digitonin-permeabilized cells to the same extent and at the same rate as lactate dehydrogenase (LDH), indicating cytosolic location of the indicator. Aequorin expressing cells treated with agonists of endogenous receptors were used in luminescence measurements to demonstrate that the reporter lines offer a highly sensitive and robust means of assaying changes in the concentration of cytosolic Ca2+ ion. Transient co-expression of the substance P receptor in aequorin reporter cells was also performed to demonstrate the feasibility of using this convenient and sensitive assay system for large scale screening of ligands that activate cell surface receptors coupled to increases in intracellular Ca2+. RP BUTTON, D (reprint author), NIMH,CELL BIOL LAB,BLDG 36,RM 3A24,BETHESDA,MD 20892, USA. RI Brownstein, Michael/B-8609-2009 NR 20 TC 70 Z9 71 U1 1 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD OCT PY 1993 VL 14 IS 9 BP 663 EP 671 DI 10.1016/0143-4160(93)90091-J PG 9 WC Cell Biology SC Cell Biology GA LZ959 UT WOS:A1993LZ95900005 PM 7694803 ER PT J AU GERADTS, J CHEN, JY RUSSELL, EK YANKASKAS, JR NIEVES, L MINNA, JD AF GERADTS, J CHEN, JY RUSSELL, EK YANKASKAS, JR NIEVES, L MINNA, JD TI HUMAN LUNG-CANCER CELL-LINES EXHIBIT RESISTANCE TO RETINOIC ACID TREATMENT SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID HUMAN HEPATOCELLULAR-CARCINOMA; ACUTE PROMYELOCYTIC LEUKEMIA; BRONCHIAL EPITHELIAL-CELLS; HEPATITIS-B VIRUS; RECEPTOR-BETA; VITAMIN-A; LIGAND REGULATION; EXPRESSION; DIFFERENTIATION; GROWTH AB Retinoic acid (RA) and nuclear retinoic acid receptors (RARs) have been implicated in a variety of human malignancies including lung cancer, and RA has been proposed as a chemopreventive agent for bronchogenic carcinoma. Normal human tracheobronchial epithelial cells show dramatic induction of RAR-beta mRNA and significant growth inhibition after RA treatment. In contrast, 17 of 22 small cell lung cancer (SCLC) and 9 of 15 non-SCLC lines treated with 1 muM RA showed no significant growth inhibition. Of interest, 5 SCLC lines with high levels of myc gene family expression related to c-, N-, or L-myc gene amplification exhibited growth inhibition (28-87%), whereas 2 non-SCLC lines actually showed growth stimulation after treatment with 1 muM RA. The lines varied greatly in their constitutive expression of RAR-beta mRNA, and 15 of 20 SCLC and 8 of 15 non-SCLC lines failed to show RAR-beta mRNA induction after RA treatment. Six cell lines showed possible alterations in the coding region of RAR-beta by complementary DNA (cDNA)/polymerase chain reaction (PCR) analysis using primers common to the RAR-beta1,2,3 isoforms, since other regions would undergo cDNA/PCR amplification whereas the DNA binding domain would not. Nonetheless, no abnormal band shift patterns in cDNA amplified by PCR were found by single strand conformation polymorphism analysis covering all 1344 base pairs of the RAR-beta open reading frame. Finally, no abnormalities in RAR-alpha gene structure or expression were identified by Southern and Northern blot analysis, including lines with cytogenetic abnormalities of 17q21. We conclude that abnormalities of the RAR-beta system are common in human lung cancer cell lines. C1 UNIV TEXAS, SW MED CTR, SIMMONS COMPREHENS CANC CTR, 5323 HARRY HINES BLVD, DALLAS, TX 75235 USA. NATL NAVAL MED CTR, NCI, NAVY MED ONCOL BRANCH, BETHESDA, MD 20814 USA. UNIV N CAROLINA, DIV PULM DIS, CHAPEL HILL, NC 27599 USA. NR 61 TC 122 Z9 127 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 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD OCT PY 1993 VL 4 IS 10 BP 799 EP 809 PG 11 WC Cell Biology SC Cell Biology GA MA997 UT WOS:A1993MA99700002 PM 8274449 ER PT J AU DENICOLA, AF SELTZER, A TSUTSUMI, K SAAVEDRA, JM AF DENICOLA, AF SELTZER, A TSUTSUMI, K SAAVEDRA, JM TI EFFECTS OF DEOXYCORTICOSTERONE ACETATE (DOCA) AND ALDOSTERONE ON SAR(1)- ANGIOTENSIN-II BINDING AND ANGIOTENSIN-CONVERTING ENZYME BINDING-SITES IN BRAIN SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE DEOXYCORTICOSTERONE; ALDOSTERONE; ADRENALECTOMY; ANGIOTENSIN II RECEPTORS; ANGIOTENSIN CONVERTING ENZYME; SALT APPETITE ID SALT APPETITE; SODIUM APPETITE; INTRACEREBROVENTRICULAR INFUSION; RECEPTOR SUBTYPES; RAT-BRAIN; MINERALOCORTICOIDS; PITUITARY; SYSTEM; NUCLEI AB 1. It is known that regulation of salt appetite is a complex behavior controlled in the brain by interaction of mineralocorticoids (MC) and angiotensin II (ANGII). To investigate the effects of MC on ANGII receptors and ANGII synthesis, we have studied two models of salt appetite control. 2. In the first model, doses of DOCA sufficient to induce salt appetite of intact rats were given. In the second one, we studied the effects of aldosterone (ALDO) in doses sufficient to suppress salt appetite developed by prior adrenalectomy (ADX). 3. Binding to ANGII receptors was determined in brain sections incubated with 3 nM [I-125]Sar(1) ANGII, exposed to [H-3]Hyperfilm with an optical density of autoradiograms measured by computerized densitometry. Sar(1)-ANGII binding was increased by DOCA treatment in the median preoptic nucleus (MnPO) and subfornical organ (SFO) but not in the paraventricular nucleus (PVN) in comparison to vehicle-treated rats. ALDO treatment was without effect on the MnPO but increased ANGII binding in the SFO and PVN. Neither hormone affected binding in the median eminence or anterior pituitary (AP). 4. In contrast to effects on Sar(1)-ANGII binding in selected areas, [I-125]351A binding to angiotensin-converting enzyme (ACE) was unchanged by DOCA or ALDO administration in the SFO, caudate putamen, AP, or posterior pituitary. 5. These findings suggest that MC modulation of the renin-angiotensin system is exerted at the central, and not at the pituitary level. ANGII receptors were modulated in a dose- and region-specific manner: while DOCA may promote their actions upon the MnPO and SFO, ALDO actions may occur at the PVN and SFO. This mechanism may not require increased generation of ANGII in the brain or pituitary. C1 NIMH,CLIN SCI LAB,PHARMACOL SECT,BETHESDA,MD 20892. RP DENICOLA, AF (reprint author), INST BIOL & MED EXPTL,NEUROENDOCRINE BIOCHEM LAB,OBLIGADO 2490,RA-1428 BUENOS AIRES,DF,ARGENTINA. NR 40 TC 32 Z9 32 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD OCT PY 1993 VL 13 IS 5 BP 529 EP 539 PG 11 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA MM970 UT WOS:A1993MM97000005 PM 8111824 ER PT J AU IOANNIDES, CG FISK, B FAN, D BIDDISON, WE WHARTON, JT OBRIAN, CA AF IOANNIDES, CG FISK, B FAN, D BIDDISON, WE WHARTON, JT OBRIAN, CA TI CYTOTOXIC T-CELLS ISOLATED FROM OVARIAN MALIGNANT ASCITES RECOGNIZE A PEPTIDE DERIVED FROM THE HER-2/NEU PROTOONCOGENE SO CELLULAR IMMUNOLOGY LA English DT Note ID BREAST-CANCER; LYMPHOCYTES; RECEPTOR; ANTIGENS; EPITOPES; IDENTIFICATION; EXPRESSION; MUTATIONS; MOLECULES; PROTEINS C1 NIH,BETHESDA,MD 20892. NIND,NEUROIMMUNOL BRANCH,MOLEC IMMUNOL SECT,BETHESDA,MD 20892. MD ANDERSON CANC CTR,DEPT CELL BIOL,HOUSTON,TX 77030. RP IOANNIDES, CG (reprint author), MD ANDERSON CANC CTR,DEPT GYNECOL ONCOL,1515 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. FU NCI NIH HHS [CA57293] NR 28 TC 116 Z9 116 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD OCT 1 PY 1993 VL 151 IS 1 BP 225 EP 234 DI 10.1006/cimm.1993.1233 PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA MB225 UT WOS:A1993MB22500017 PM 7691418 ER PT J AU MARKOVIC, M FOWLER, BO BROWN, WE AF MARKOVIC, M FOWLER, BO BROWN, WE TI OCTACALCIUM PHOSPHATE CARBOXYLATES .1. PREPARATION AND IDENTIFICATION SO CHEMISTRY OF MATERIALS LA English DT Article AB The formation of octacalcium phosphate carboxylates, Ca8(HPO4)m(carboxylate)n(PO4)4.yH2O, by conversion of alpha-Ca3(PO4)2 in solutions of 19 ammonium carboxylates (monocarboxylates; saturated, unsaturated, hydroxy, keto, and amino dicarboxylates; and tricarboxylates) was investigated. The various solid phases formed, depending on initial pH's and conversion times, were determined by X-ray diffraction and infrared and Raman spectroscopy. Octacalcium phosphate carboxylates containing structurally incorporated malonate, succinate, adipate, suberate, sebacate, fumarate, malate, and citrate ions were formed and identified. Octacalcium phosphate carboxylates were also formed from pyruvate and alpha-ketoglutarate solutions but with uncertain carboxylate ion structures. All of these identified compounds are structurally similar to octacalcium phosphate, Ca8(HPO4)2(PO4)4-5H2O, but have expanded a-axis unit-cell dimensions that generally increased with increasing number of carbon atoms in the carboxylate ion. Among these compounds, of special importance are those containing carboxylates that are present as intermediates in the Krebs cycle. The possible precipitation of these octacalcium phosphate carboxylates in mitochondria and their possible role as precursors in calcified tissue formation are discussed. C1 NATL INST STAND & TECHNOL,NIDR,BONE RES BRANCH,RES PROGRAM,GAITHERSBURG,MD 20899. RP MARKOVIC, M (reprint author), NATL INST STAND & TECHNOL,AMER DENT ASSOC,HLTH FDN,PAFFENBARGER RES CTR,GAITHERSBURG,MD 20899, USA. NR 32 TC 20 Z9 20 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0897-4756 J9 CHEM MATER JI Chem. Mat. PD OCT PY 1993 VL 5 IS 10 BP 1401 EP 1405 DI 10.1021/cm00034a007 PG 5 WC Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA MC690 UT WOS:A1993MC69000007 ER PT J AU MARKOVIC, M FOWLER, BO BROWN, WE AF MARKOVIC, M FOWLER, BO BROWN, WE TI OCTACALCIUM PHOSPHATE CARBOXYLATES .2. CHARACTERIZATION AND STRUCTURAL CONSIDERATIONS SO CHEMISTRY OF MATERIALS LA English DT Article AB Detailed physicochemical characterization of octacalcium phosphate carboxylates (OCPCs) with structurally incorporated succinate, adipate, suberate, sebacate, fumarate, and citrate ions is reported. Compositional formulas of the OCPCs were derived from Ca, P, C, H, and H2O analyses. In octacalcium phosphate dicarboxylates with the general formula Ca8(HPO4)2-x(dicarboxylate)x(PO4)4.yH2O, a maximum of one HPO42- was replaced by a dicarboxylate ion (x less-than-or-equal-to 1). The water content increased with increasing chain length of the dicarboxylate ion (5.7 less-than-or-equal-to y less-than-or-equal-to 8.0). For octacalcium phosphate tricarboxylate, Ca8(HPO4)2-1.5x(tricarboxylate)x(PO4)4.yH2O, with incorporated citrate ions the values of x and y were 0.4 and 7.8, respectively. X-ray diffraction patterns of OCPCs show structural similarity with the parent compound octacalcium phosphate (OCP); the b and c axes of the unit cells were nearly the same as those of OCP but the a axes were progressively expanded concomitant with carbon chain length. Infrared and Raman assignments were made for nearly all bands of these six OCPCs; an OCP-succinate containing the deuterated succinate ion was prepared to facilitate band assignments. Spectra of the OCPCs, as compared to that of OCP, showed the presence of carboxylate groups, changes in water bonding, only slight changes in PO4 environments, and preferential reduction in HPO4(5) content. OCP has two crystallographically nonequivalent HPO4 groups (designated 5 and 6); the preferential replacement of HPO4(5) by the dicarboxylate ion is plausible considering lattice geometry. By utilizing combined data from the different methods, the possible positions of carboxylate ions in the OCPC structures are discussed. C1 NATL INST STAND & TECHNOL,NIDR,BONE RES BRANCH,RES PROGRAM,GAITHRSBURG,MD 20899. RP MARKOVIC, M (reprint author), NATL INST STAND & TECHNOL,AMER DENT ASSOC,HLTH FDN,PAFFENBARGER RES CTR,GAITHERSBURG,MD 20899, USA. NR 19 TC 24 Z9 24 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0897-4756 J9 CHEM MATER JI Chem. Mat. PD OCT PY 1993 VL 5 IS 10 BP 1406 EP 1416 DI 10.1021/cm00034a008 PG 11 WC Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA MC690 UT WOS:A1993MC69000008 ER PT J AU FOWLER, BO MARKOVIC, M BROWN, WE AF FOWLER, BO MARKOVIC, M BROWN, WE TI OCTACALCIUM PHOSPHATE .3. INFRARED AND RAMAN VIBRATIONAL-SPECTRA SO CHEMISTRY OF MATERIALS LA English DT Article ID BARIUM HYDROXYAPATITES; APATITES; SPECTROSCOPY; STRONTIUM; CALCIUM AB Infrared and Raman band assignments are given for powdered samples of the biologically important compound, octacalcium phosphate, in the 4000-300-cm-1 range. Specific assignments were made for bands of the two crystallographically independent acidic phosphate groups. The numbers of observed bands were markedly less than those predicted by factor group analysis; additional unresolved bands are probably present. Infrared spectra indicate that two polymorphs of octacalcium phosphate may exist whose structures differ mainly in acidic phosphate and water bonding and in possibly different contents of water. Polymorphic forms of octacalcium phosphate are structurally plausible because of possible differences in bonding of its acidic phosphate groups and water molecules and in number of water molecules. The wavenumber positions of Raman bands, especially acidic phosphate bands, were sensitive to laser excitation power. C1 NATL INST STAND & TECHNOL,AMER DENT ASSOC,HLTH FDN,PAFFENBARGER RES CTR,GAITHERSBURG,MD 20899. RP FOWLER, BO (reprint author), NATL INST STAND & TECHNOL,NIDR,BONE RES BRANCH,RES PROGRAM,GAITHERSBURG,MD 20899, USA. NR 26 TC 104 Z9 105 U1 3 U2 29 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0897-4756 J9 CHEM MATER JI Chem. Mat. PD OCT PY 1993 VL 5 IS 10 BP 1417 EP 1423 DI 10.1021/cm00034a009 PG 7 WC Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA MC690 UT WOS:A1993MC69000009 ER PT J AU PLOMIN, R EMDE, RN BRAUNGART, JM CAMPOS, J CORLEY, R FULKER, DW KAGAN, J REZNICK, JS ROBINSON, J ZAHNWAXLER, C DEFRIES, JC AF PLOMIN, R EMDE, RN BRAUNGART, JM CAMPOS, J CORLEY, R FULKER, DW KAGAN, J REZNICK, JS ROBINSON, J ZAHNWAXLER, C DEFRIES, JC TI GENETIC CHANGE AND CONTINUITY FROM 14 TO 20 MONTHS - THE MACARTHUR LONGITUDINAL TWIN STUDY SO CHILD DEVELOPMENT LA English DT Article ID MULTIPLE-REGRESSION ANALYSIS; INFANT BEHAVIOR RECORD; CHILDHOOD; TEMPERAMENT; PERSONALITY; COMPONENTS; STABILITY; ADULTHOOD AB Genetic change as well as continuity was investigated within the domains of temperament, emotion, and cognition/language for 200 pairs of twins assessed at 14 and 20 months of age in the laboratory and home. The second year of life is marked by change rather than continuity: correlations from 14 to 20 months averaged about .30 for observational measures of temperament and emotion, about .40 for language measures, and about .50 for mental development. 2 types of genetic change were examined: changes in the magnitude of genetic influence (heritability) and genetic contributions to change from 14 to 20 months. In general, heritability estimates were similar at 14 and 20 months. Evidence for genetic influence on change from 14 to 20 months emerged for several measures, implying that heritability cannot be equated with stability. Analyses of continuity indicated that genetic factors are largely responsible for continuity from 14 to 20 months. C1 HARVARD UNIV,CAMBRIDGE,MA 02138. UNIV COLORADO,HLTH SCI CTR,DENVER,CO 80262. YALE UNIV,NEW HAVEN,CT 06520. UNIV CALIF BERKELEY,BERKELEY,CA 94720. NIMH,WASHINGTON,DC 20032. UNIV COLORADO,BOULDER,CO 80309. RP PLOMIN, R (reprint author), PENN STATE UNIV,CTR DEV & HLTH GENET,S-211 HENDERDON BLDG,UNIV PK,PA 16802, USA. RI Plomin, Robert/B-8911-2008; OI Plomin, Robert/0000-0002-0756-3629 FU NIMH NIH HHS [5 K02 MH36808] NR 52 TC 152 Z9 153 U1 1 U2 7 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0009-3920 J9 CHILD DEV JI Child Dev. PD OCT PY 1993 VL 64 IS 5 BP 1354 EP 1376 DI 10.1111/j.1467-8624.1993.tb02957.x PG 23 WC Psychology, Educational; Psychology, Developmental SC Psychology GA MC128 UT WOS:A1993MC12800004 PM 8222877 ER PT J AU HOEG, JM VAISMAN, BL DEMOSKY, SJ SANTAMARINAFOJO, S BREWER, HB REMALEY, AT HOYT, RF FELDMAN, S AF HOEG, JM VAISMAN, BL DEMOSKY, SJ SANTAMARINAFOJO, S BREWER, HB REMALEY, AT HOYT, RF FELDMAN, S TI DEVELOPMENT OF TRANSGENIC WATANABE HERITABLE HYPERLIPIDEMIC RABBITS EXPRESSING HUMAN APOLIPOPROTEIN-A-I SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 2 EP 2 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200052 ER PT J AU IRANI, K FINKEL, T AF IRANI, K FINKEL, T TI RAS REGULATES MITOGENIC SIGNALING IN SMOOTH-MUSCLE CELLS SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 3 EP 3 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200056 ER PT J AU PAULY, RR MONTICONE, R SOLLOTT, S ZHENG, JS LAKATTA, EG SUZUKI, T CROW, MT AF PAULY, RR MONTICONE, R SOLLOTT, S ZHENG, JS LAKATTA, EG SUZUKI, T CROW, MT TI THE INTRACELLULAR SIGNALING PATHWAY FOR THE PDGF-INDUCED MIGRATION OF VASCULAR SMOOTH-MUSCLE CELLS INVOLVES CA2+-CALMODULIN-DEPENDENT PROTEIN KINASE-II SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NAGOYA CITY UNIV,SCH MED,NAGOYA,AICHI 467,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 4 EP 4 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200058 ER PT J AU SHAH, AM SILVERMAN, HS LAKATTA, EG AF SHAH, AM SILVERMAN, HS LAKATTA, EG TI CYCLIC-GMP ABOLISHES RELAXATION ABNORMALITIES AT REOXYGENATION FOLLOWING BRIEF ANOXIA IN SINGLE CARDIAC MYOCYTES SO CIRCULATION LA English DT Meeting Abstract C1 NIH,GERONTOL RES CTR,BETHESDA,MD 20892. JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. UNIV WALES COLL MED,CARDIFF CF4 4XN,S GLAM,WALES. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 43 EP 43 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200259 ER PT J AU SHANDAS, R SOLOWIEJCZYK, D MANDULEY, R YAMADA, I CAYRE, R VALDESCRUZ, L AF SHANDAS, R SOLOWIEJCZYK, D MANDULEY, R YAMADA, I CAYRE, R VALDESCRUZ, L TI ACCURACY OF AN AUTOMATIC COMPUTER ALGORITHM FOR CALCULATION OF FLOWS THROUGH BILEAFLET MECHANICAL MITRAL-VALVES BASED ON THE FLOW CONVERGENCE METHOD - STUDIES IN A CHRONIC ANIMAL-MODEL SO CIRCULATION LA English DT Meeting Abstract C1 MAIMONIDES HOSP,BROOKLYN,NY 11219. NHLBI,LAMS,BETHESDA,MD 20892. COLUMBIA UNIV,NEW YORK,NY 10027. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 49 EP 49 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200290 ER PT J AU MARON, BJ SHIRANI, J MUELLER, FO CANTU, RC ROBERTS, WC AF MARON, BJ SHIRANI, J MUELLER, FO CANTU, RC ROBERTS, WC TI CARDIOVASCULAR CAUSES OF ATHLETIC FIELD DEATHS - ANALYSIS OF SUDDEN-DEATH IN 84 COMPETITIVE ATHLETES SO CIRCULATION LA English DT Meeting Abstract C1 MINNEAPOLIS HEART INST FDN,MINNEAPOLIS,MN. NHLBI,BETHESDA,MD 20892. UNIV N CAROLINA,CHAPEL HILL,NC 27514. EMERSON HOSP,CONCORD,MA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 50 EP 50 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200299 ER PT J AU IKEWAKI, K RADER, DJ ZECH, LA BREWER, HB AF IKEWAKI, K RADER, DJ ZECH, LA BREWER, HB TI HDL METABOLISM IN ABETALIPOPROTEINEMIA - ACCELERATED CATABOLISM OF HDL CONTAINING APOA-I AND APOE SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,MDB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 75 EP 75 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200430 ER PT J AU SHAMBUREK, RD NISHIWAKI, M ISHIKAWA, T NAKAMURA, H IKEWAKI, K ZECH, LA RADER, DJ BREWER, HB SCHWARTZ, CC AF SHAMBUREK, RD NISHIWAKI, M ISHIKAWA, T NAKAMURA, H IKEWAKI, K ZECH, LA RADER, DJ BREWER, HB SCHWARTZ, CC TI CHOLESTERYL ESTER TRANSFER PROTEIN-DEFICIENCY - IN-VIVO METABOLISM OF FREE AND ESTERIFIED CHOLESTEROL SO CIRCULATION LA English DT Meeting Abstract C1 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,RICHMOND,VA 23298. NHLBI,BETHESDA,MD 20892. NR 0 TC 3 Z9 3 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 75 EP 75 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200431 ER PT J AU ROUIS, M PREVIATO, L GOLDBERG, I GINSBERG, H BRUNZELL, JD BREWER, HB SANTAMARINAFOJO, S AF ROUIS, M PREVIATO, L GOLDBERG, I GINSBERG, H BRUNZELL, JD BREWER, HB SANTAMARINAFOJO, S TI UNIQUE THERAPEUTIC RESPONSE TO MEDIUM-CHAIN TRIGLYCERIDES AND OMEGA-3-FATTY-ACIDS IN 2 PATIENTS WITH FAMILIAL CHYLOMICRONEMIA SO CIRCULATION LA English DT Meeting Abstract C1 NIH,MDB,BETHESDA,MD 20892. COLUMBIA UNIV,NEW YORK,NY 10027. UNIV WASHINGTON,SEATTLE,WA 98195. RI Rouis, Mustapha/E-4993-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 76 EP 76 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200439 ER PT J AU GILLIGAN, DM QUYYUMI, AA JOHNSON, GB CANNON, RO AF GILLIGAN, DM QUYYUMI, AA JOHNSON, GB CANNON, RO TI ESTRADIOL ACUTELY POTENTIATES CORONARY ENDOTHELIUM-DEPENDENT VASODILATION IN POSTMENOPAUSAL WOMEN SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 9 Z9 9 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 79 EP 79 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200457 ER PT J AU GILLIGAN, DM BADAR, DA PANZA, JA QUYYUMI, AA CANNON, RO AF GILLIGAN, DM BADAR, DA PANZA, JA QUYYUMI, AA CANNON, RO TI THE EFFECTS OF ESTROGEN ON ENDOTHELIUM-DEPENDENT VASODILATION IN POSTMENOPAUSAL WOMEN SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 9 Z9 9 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 79 EP 79 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200456 ER PT J AU GUZMAN, RJ LEMARCHAND, P CRYSTAL, RG EPSTEIN, SE FINKEL, T AF GUZMAN, RJ LEMARCHAND, P CRYSTAL, RG EPSTEIN, SE FINKEL, T TI EFFICIENT AND SELECTIVE ADENOVIRAL-MEDIATED GENE-TRANSFER INTO VASCULAR NEOINTIMA SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 80 EP 80 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200462 ER PT J AU ROME, JJ SHAYANI, V NEWMAN, KD LEE, SW VIRMANI, R DICHEK, DA AF ROME, JJ SHAYANI, V NEWMAN, KD LEE, SW VIRMANI, R DICHEK, DA TI ADENOVIRAL VECTOR-MEDIATED GENE-TRANSFER INTO SHEEP CAROTID ARTERIES USING A DOUBLE-BALLOON CATHETER SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 80 EP 80 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200461 ER PT J AU SHAH, AM MEBAZAA, A LAKATTA, EG AF SHAH, AM MEBAZAA, A LAKATTA, EG TI FACTORS RELEASED BY ENDOTHELIAL-CELLS MODULATE CARDIAC DIASTOLIC TONE SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. JOHNS HOPKINS MED INST,PULM ANESTH LAB,BALTIMORE,MD 21205. UNIV WALES COLL MED,CARDIFF CF4 4XN,S GLAM,WALES. NR 0 TC 3 Z9 3 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 86 EP 86 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200492 ER PT J AU ZHENG, JS BOLUYT, MO ZIMAN, B LONG, XL ONEILL, L CROW, MT LAKATTA, EG AF ZHENG, JS BOLUYT, MO ZIMAN, B LONG, XL ONEILL, L CROW, MT LAKATTA, EG TI EXTRACELLULAR ATP INDUCES C-FOS GENE-EXPRESSION VIA A CA-2+-DEPENDENT PATHWAY IN CULTURED CARDIAC MYOCYTES AND FIBROBLASTS SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GRC,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 92 EP 92 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200527 ER PT J AU FRALIX, TA STEENBERGEN, C MURPHY, E AF FRALIX, TA STEENBERGEN, C MURPHY, E TI ROLE OF PHOSPHATASES IN PRECONDITIONING IN ISOLATED RAT-HEART SO CIRCULATION LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. DUKE UNIV,DURHAM,NC 27706. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 101 EP 101 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200575 ER PT J AU RUNDQUIST, B ELAM, M EISENHOFER, G WAAGSTEIN, F FRIBERG, P AF RUNDQUIST, B ELAM, M EISENHOFER, G WAAGSTEIN, F FRIBERG, P TI INCREASED TOTAL AND REGIONAL SYMPATHETIC-NERVE ACTIVITY IN CONGESTIVE-HEART-FAILURE (CHF) RETURNS TO NORMAL FOLLOWING CARDIAC TRANSPLANTATION SO CIRCULATION LA English DT Meeting Abstract C1 GOTHENBURG UNIV,SAHLGRENS HOSP,DEPT CARDIOL,S-41345 GOTHENBURG,SWEDEN. GOTHENBURG UNIV,SAHLGRENS HOSP,DEPT CLIN PHYSIOL,S-41345 GOTHENBURG,SWEDEN. GOTHENBURG UNIV,SAHLGRENS HOSP,DEPT NEUROPHYSIOL,S-41345 GOTHENBURG,SWEDEN. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 108 EP 108 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200614 ER PT J AU SHIOTA, T GONG, Z PASSAFINI, A SAHN, DJ JONES, M YAMADA, I AF SHIOTA, T GONG, Z PASSAFINI, A SAHN, DJ JONES, M YAMADA, I TI METHODS FOR ESTIMATING DYNAMIC ORIFICE SIZE IN FLAIL LEAFLET-TYPE MITRAL REGURGITATION - AN ANIMAL STUDY SO CIRCULATION LA English DT Meeting Abstract C1 OREGON HLTH SCI UNIV,PORTLAND,OR 97201. NHLBI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 109 EP 109 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200618 ER PT J AU YAMADA, I SHIOTA, T JONES, M TEIEN, D SHANDAS, R SAHN, DJ AF YAMADA, I SHIOTA, T JONES, M TEIEN, D SHANDAS, R SAHN, DJ TI A DIGITAL COLOR DOPPLER METHOD FOR EVALUATION OF MITRAL REGURGITATION - VALIDATION IN SHEEP WITH QUANTIFIABLE PROLAPSE TYPE MITRAL REGURGITATION SO CIRCULATION LA English DT Meeting Abstract C1 NIH,LAMS,BETHESDA,MD 20892. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 110 EP 110 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200623 ER PT J AU BYRNE, EA FLEG, JL VAITKEVICIUS, PV WRIGHT, J PORGES, SW AF BYRNE, EA FLEG, JL VAITKEVICIUS, PV WRIGHT, J PORGES, SW TI ROLE OF AEROBIC CAPACITY AND RELATIVE WEIGHT IN THE AGE-ASSOCIATED DECLINE IN RESPIRATORY SINUS ARRHYTHMIA SO CIRCULATION LA English DT Meeting Abstract C1 UNIV MARYLAND,COLL PK,MD 20742. NIA,GERONTOL RES CTR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 115 EP 115 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200650 ER PT J AU SAVAGE, PJ WAHL, PW TRACY, RP BORHANI, NO AF SAVAGE, PJ WAHL, PW TRACY, RP BORHANI, NO TI FREQUENCY OF HYPERGLYCEMIA AND HYPERINSULINEMIA AMONG ELDERLY WOMEN AND MEN - THE CHS STUDY SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 124 EP 124 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200701 ER PT J AU GAMBASSI, G VENEMA, R ZIMAN, BD CAPOGROSSI, MC AF GAMBASSI, G VENEMA, R ZIMAN, BD CAPOGROSSI, MC TI OPPOSITE EFFECTS OF 2-3 BUTANEDIONE MONOXIME (BDM) AND CALYCULIN-A ON MYOFILAMENT CA2+ SENSITIVITY AND MYOSIN LIGHT CHAIN-2 PHOSPHORYLATION SO CIRCULATION LA English DT Meeting Abstract C1 NIA,CARDIOVASC SCI LAB,BETHESDA,MD 20892. EMORY UNIV,DEPT MED,DIV CARDIOL,ATLANTA,GA 30322. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 135 EP 135 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200756 ER PT J AU GAMBASSI, G SPURGEON, HA CAPOGROSSI, MC AF GAMBASSI, G SPURGEON, HA CAPOGROSSI, MC TI CA2+-DEPENDENCE OF THE EFFECT OF ALPHA(1)-ADRENERGIC RECEPTOR SUBTYPES ON CONTRACTILITY AND CYTOSOLIC CA2+ OF SINGLE CARDIAC-CELLS SO CIRCULATION LA English DT Meeting Abstract C1 NIA,CARDIOVASC SCI LAB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 136 EP 136 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200758 ER PT J AU KOMURO, I INAGAKI, H COEPLAND, N JENKINS, N IZUMO, S AF KOMURO, I INAGAKI, H COEPLAND, N JENKINS, N IZUMO, S TI 2 NOVEL HOMEOBOX-CONTAINING GENES, KBX AND IMX, ARE LOCALIZED TANDEMLY ON MOUSE CHROMOSOME-14 SO CIRCULATION LA English DT Meeting Abstract C1 BETH ISRAEL HOSP,BOSTON,MA 02215. NCI,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 140 EP 140 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200783 ER PT J AU SHAYANI, V NEWMAN, KD DICHEK, DA AF SHAYANI, V NEWMAN, KD DICHEK, DA TI OPTIMIZATION OF TISSUE-PLASMINOGEN ACTIVATOR SECRETION FROM ENDOTHELIAL CELL-SEEDED VASCULAR GRAFTS SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 147 EP 147 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200822 ER PT J AU SPEIR, E MODALI, R SHAWL, F FINKEL, T HUANG, ES EPSTEIN, SE AF SPEIR, E MODALI, R SHAWL, F FINKEL, T HUANG, ES EPSTEIN, SE TI HUMAN CYTOMEGALOVIRUS IN RESTENOSIS - INTERACTION WITH THE TUMOR-SUPPRESSOR GENE P53 SO CIRCULATION LA English DT Meeting Abstract C1 UNC,CHAPEL HILL,NC. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 151 EP 151 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200840 ER PT J AU PAULY, RR MONTICONE, R LAKATTA, EG CROW, MT AF PAULY, RR MONTICONE, R LAKATTA, EG CROW, MT TI THE MIGRATION OF VASCULAR SMOOTH-MUSCLE CELLS THROUGH A RECONSTITUTED BASEMENT-MEMBRANE BARRIER REQUIRES 72-KD TYPE-IV GELATINASE AND IS SUPPRESSED BY DIFFERENTIATION SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 174 EP 174 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200965 ER PT J AU BRAND, K DUGI, KA BRUNZELL, JD NEVIN, DN BREWER, HB SANTAMARINAFOJO, S AF BRAND, K DUGI, KA BRUNZELL, JD NEVIN, DN BREWER, HB SANTAMARINAFOJO, S TI ALTERNATIVE SPLICING - A NOVEL MECHANISM LEADING TO DEFICIENCY OF HEPATIC LIPASE SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. UNIV WASHINGTON,SEATTLE,WA 98195. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 178 EP 178 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200986 ER PT J AU DUGI, KA DICHEK, HL BREWER, HB SANTAMARINAFOJO, S AF DUGI, KA DICHEK, HL BREWER, HB SANTAMARINAFOJO, S TI NEW INSIGHTS INTO THE STRUCTURAL BASIS FOR THE DIFFERENT SUBSTRATE SPECIFICITIES OF HEPATIC LIPASE AND LIPOPROTEIN-LIPASE SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 178 EP 178 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68200985 ER PT J AU DILSIZIAN, V BONOW, RO QUYYUMI, AA SMELTZER, WR BACHARACH, SL AF DILSIZIAN, V BONOW, RO QUYYUMI, AA SMELTZER, WR BACHARACH, SL TI IS EARLY THALLIUM REINJECTION AFTER POSTEXERCISE IMAGING A SATISFACTORY METHOD TO DETECT DEFECT REVERSIBILITY SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 199 EP 199 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68201104 ER PT J AU MCAREAVEY, D DILSIZIAN, V PANZA, J AF MCAREAVEY, D DILSIZIAN, V PANZA, J TI FAVORABLE PROGNOSIS IN 88 YOUNG HYPERTROPHIC CARDIOMYOPATHY PATIENTS DURING THERAPY BASED ON HEMODYNAMIC, ELECTROPHYSIOLOGIC AND THALLIUM SCINTIGRAPHY FINDINGS SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 209 EP 209 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68201157 ER PT J AU FANANAPAZIR, L TRIPODI, D MCAREAVEY, D AF FANANAPAZIR, L TRIPODI, D MCAREAVEY, D TI RATE-RESPONSIVE VENTRICULAR PACING IMPROVES DRUG-REFRACTORY SYMPTOMS AND HEMODYNAMIC INDEXES IN NONOBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY FOLLOWING RADIOFREQUENCY ABLATION OF ATRIOVENTRICULAR NODE FOR CHRONIC ATRIAL-FIBRILLATION SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 210 EP 210 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68201161 ER PT J AU KLUES, HG SCHIFFERS, A MARON, BJ AF KLUES, HG SCHIFFERS, A MARON, BJ TI PATTERNS OF HYPERTROPHY AND MORPHOLOGIC SPECTRUM IN 600 PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY SO CIRCULATION LA English DT Meeting Abstract C1 RHEIN WESTFAL TH AACHEN,W-5100 AACHEN,GERMANY. NHLBI,BETHESDA,MD 20892. MINNEAPOLIS HEART INST FDN,MINNEAPOLIS,MN. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 211 EP 211 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68201167 ER PT J AU ZHENG, JS BOLUYT, MO DAI, YS LI, J LONG, XL BAUM, BJ CROW, MT AF ZHENG, JS BOLUYT, MO DAI, YS LI, J LONG, XL BAUM, BJ CROW, MT TI EXPRESSION OF CHIP28 WATER CHANNEL IN AORTIC-CONSTRICTED RAT-HEART SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GRC,BALTIMORE,MD 21224. NIDR,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 232 EP 232 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68201279 ER PT J AU BALABAN, RS TAYLOR, J TURNER, R AF BALABAN, RS TAYLOR, J TURNER, R TI EFFECTS OF CORONARY FLOW AND VENOUS HEMOGLOBIN SATURATION ON MRI SIGNAL INTENSITY IN THE CANINE MYOCARDIUM, IN-VIVO SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. RI Turner, Robert/C-1820-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 236 EP 236 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68201305 ER PT J AU MURAKAMI, T HERMOUET, S SPIEGEL, AM AF MURAKAMI, T HERMOUET, S SPIEGEL, AM TI STABLE TRANSFECTION OF WILD-TYPE, CONSTITUTIVELY ACTIVATED AND INACTIVATED GI-ALPHA-S AND GQ-ALPHA HAS AN EFFECT ON EXPRESSION OF BETA-1 AND BETA-2 SUBUNITS OF G-PROTEINS SO CIRCULATION LA English DT Meeting Abstract C1 HOKKAIDO UNIV,DEPT CARDIOVASC MED,SAPPORO,HOKKAIDO 060,JAPAN. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 242 EP 242 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68201338 ER PT J AU RADER, DJ CAIN, W IKEWAKI, K USHER, D ZECH, LA BREWER, HB AF RADER, DJ CAIN, W IKEWAKI, K USHER, D ZECH, LA BREWER, HB TI THE INVERSE ASSOCIATION OF LP(A) LEVELS WITH APO(A) ISOFORM SIZE IS DUE TO DIFFERENCES IN LP(A) PRODUCTION AND NOT CATABOLIC RATE SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,MDB,BETHESDA,MD 20892. UNIV DELAWARE,NEWARK,DE 19718. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 271 EP 271 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68201489 ER PT J AU SCHOLZ, TD HOYT, RF DELEONARDIS, JR CECKLER, TL BALABAN, RS AF SCHOLZ, TD HOYT, RF DELEONARDIS, JR CECKLER, TL BALABAN, RS TI MAGNETIZATION-TRANSFER IN INFARCTED MYOCARDIUM - A MECHANISM TO ENHANCE MAGNETIC-RESONANCE IMAGE-CONTRAST SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 275 EP 275 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68201508 ER PT J AU XIAO, RP SUZUKI, T CHENG, HP LEDERER, J LAKATTA, EG AF XIAO, RP SUZUKI, T CHENG, HP LEDERER, J LAKATTA, EG TI CA2+-CALMODULIN-DEPENDENT PROTEIN KINASE-II MEDIATES FACILITATION OF I(CA) IN RAT CARDIAC VENTRICULAR CELLS SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 2 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 278 EP 278 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68201528 ER PT J AU GAMBASSI, G SPURGEON, HA CAPOGROSSI, MC AF GAMBASSI, G SPURGEON, HA CAPOGROSSI, MC TI ALPHA(1A-)-ADRENOCEPTOR AND ALPHA(1B)-ADRENOCEPTOR DIFFERENTLY MODULATE MYOCARDIAL CA2+ HOMEOSTASIS AND MYOFILAMENT SENSITIVITY TO CA2+ SO CIRCULATION LA English DT Meeting Abstract C1 NIA,CARDIOVASC SCI LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 279 EP 279 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68201531 ER PT J AU SCHOLZ, TD TAYLOR, JL BALABAN, RS AF SCHOLZ, TD TAYLOR, JL BALABAN, RS TI MITOCHONDRIAL F1ATPASE ACTIVITY OF CANINE MYOCARDIUM - EFFECTS OF HYPOXIA AND STIMULATION SO CIRCULATION LA English DT Meeting Abstract C1 NIH,CARDIAC ENERGET LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 284 EP 284 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68201558 ER PT J AU YU, ZX FU, YM IRANI, K FINKEL, T AF YU, ZX FU, YM IRANI, K FINKEL, T TI TYROSINE KINASE INHIBITOR GENISTEIN INHIBITS PDGF-INDUCED CHEMOTAXIS BUT NOT CHEMOKINESIS SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 325 EP 325 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68201781 ER PT J AU OWENS, L GETTES, LS CASCIO, WE FRALIX, TA MURPHY, E AF OWENS, L GETTES, LS CASCIO, WE FRALIX, TA MURPHY, E TI CORRELATION OF EXTRACELLULAR AND INTRACELLULAR EVENTS DURING ACUTE-ISCHEMIA IN THE ISOLATED BLOOD-PERFUSED RABBIT HEART SO CIRCULATION LA English DT Meeting Abstract C1 UNIV N CAROLINA,CHAPEL HILL,NC 27514. NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 327 EP 327 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68201788 ER PT J AU CUDA, G SELLERS, J EPSTEIN, ND FANANAPAZIR, L AF CUDA, G SELLERS, J EPSTEIN, ND FANANAPAZIR, L TI IN-VITRO MOTILITY ACTIVITY OF BETA-CARDIAC MYOSIN DEPENDS ON THE NATURE OF THE BETA-MYOSIN HEAVY-CHAIN GENE MUTATION IN HYPERTROPHIC CARDIOMYOPATHY SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Cuda, Giovanni/F-5359-2012 OI Cuda, Giovanni/0000-0001-6313-1866 NR 0 TC 7 Z9 7 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 343 EP 343 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68201874 ER PT J AU FANANAPAZIR, L CUDA, G SELLERS, J EPSTEIN, ND AF FANANAPAZIR, L CUDA, G SELLERS, J EPSTEIN, ND TI DIFFERENCES IN MOTILITY ACTIVITY OF BETA-MYOSIN FROM SKELETAL-MUSCLE IN HYPERTROPHIC CARDIOMYOPATHY KINDREDS WITH INDEPENDENT BETA-MYOSIN HEAVY-CHAIN GENE-MUTATIONS RESULTING IN THE IDENTICAL 741 GLY-]ARG AMINO-ACID SUBSTITUTION SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Cuda, Giovanni/F-5359-2012 OI Cuda, Giovanni/0000-0001-6313-1866 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 343 EP 343 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68201875 ER PT J AU SLATER, J ATTUBATO, MJ FEIT, F BILYK, F MICKEL, M KRONZON, I AF SLATER, J ATTUBATO, MJ FEIT, F BILYK, F MICKEL, M KRONZON, I TI TEMPORARY IMPROVEMENT AFTER MITRAL BALLOON COMMISSUROTOMY - HEMODYNAMIC AND ANGIOGRAPHIC CORRELATES SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BALLOON VALVULOPLASTY REGISTRY,NEW YORK,NY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 351 EP 351 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68201917 ER PT J AU MANOLIO, TA BURKE, GL PSATY, BM HAAN, M POWE, N TRACY, RP NEWMAN, AB OLEARY, DH AF MANOLIO, TA BURKE, GL PSATY, BM HAAN, M POWE, N TRACY, RP NEWMAN, AB OLEARY, DH TI BLACK-WHITE DIFFERENCES IN SUBCLINICAL CARDIOVASCULAR-DISEASE AMONG OLDER ADULTS - THE CARDIOVASCULAR HEALTH STUDY (CHS) SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,CHS COLLABORAT RES GRP,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 357 EP 357 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68201951 ER PT J AU BAGDADE, JD RITTER, MC NAGI, D KNOWLER, W AF BAGDADE, JD RITTER, MC NAGI, D KNOWLER, W TI DOES ABERRANT PLASMA TRAFFICKING OF CHOLESTERYL ESTER EXPLAIN THE IMMUNITY OF PIMA-INDIANS TO CORONARY HEART-DISEASE (CHD) SO CIRCULATION LA English DT Meeting Abstract C1 RUSH MED COLL,CHICAGO,IL 60612. NIH,PHOENIX,AZ. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 358 EP 358 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68201957 ER PT J AU QUYYUMI, AA DAKAK, N GILLIGAN, DM ANDREWS, NP DIODATI, JG PANZA, JA CANNON, RO AF QUYYUMI, AA DAKAK, N GILLIGAN, DM ANDREWS, NP DIODATI, JG PANZA, JA CANNON, RO TI PERIPHERAL VASCULAR ENDOTHELIAL DYSFUNCTION IN SYNDROME-X PATIENTS WITH ENDOTHELIAL DYSFUNCTION OF THE CORONARY MICROVASCULATURE SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 369 EP 369 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68202016 ER PT J AU LEE, SW TRAPNELL, BC RADE, JJ VIRMANI, R DICHEK, DA AF LEE, SW TRAPNELL, BC RADE, JJ VIRMANI, R DICHEK, DA TI ADENOVIRAL-MEDIATED GENE-TRANSFER INTO THE INJURED RAT CAROTID-ARTERY SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 371 EP 371 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68202030 ER PT J AU OWENS, L MURPHY, E FRALIX, TA CASCIO, WE GETTES, LS AF OWENS, L MURPHY, E FRALIX, TA CASCIO, WE GETTES, LS TI RELATIONSHIP OF CELLULAR ELECTRICAL UNCOUPLING TO CHANGES OF CA(I), PH(I), ATP, AND CONTRACTURE IN ISCHEMIC RABBIT MYOCARDIUM SO CIRCULATION LA English DT Meeting Abstract C1 UNIV N CAROLINA,EXPTL CARDIOL GRP,CHAPEL HILL,NC 27514. NIEHS,LMB,RES TRIANGLE PK,NC 27709. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 373 EP 373 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68202038 ER PT J AU LAZAROUS, DF SHOU, M SCHEINOWITZ, M HODGE, E EPSTEIN, SE UNGER, EF AF LAZAROUS, DF SHOU, M SCHEINOWITZ, M HODGE, E EPSTEIN, SE UNGER, EF TI EFFECTS OF LONG-TERM (9-WEEK) ADMINISTRATION OF BASIC FIBROBLAST GROWTH-FACTOR ON COLLATERAL DEVELOPMENT IN ISCHEMIC CANINE MYOCARDIUM SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 375 EP 375 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68202053 ER PT J AU BOLUYT, MO ONEILL, L MEREDITH, AL BING, OHL BROOKS, WW CONRAD, CH CROW, MT LAKATTA, EG AF BOLUYT, MO ONEILL, L MEREDITH, AL BING, OHL BROOKS, WW CONRAD, CH CROW, MT LAKATTA, EG TI ELEVATED LEVELS OF TRANSFORMING GROWTH-FACTOR-BETA-1, FIBRONECTIN AND COLLAGEN MESSENGER-RNA DURING THE TRANSITION FROM STABLE HYPERTROPHY TO HEART-FAILURE SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GRC,BALTIMORE,MD 21224. VET ADM MED CTR JAMAICA PLAIN,BOSTON,MA 02130. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 380 EP 380 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68202079 ER PT J AU GAMBASSI, G LAKATTA, EG CAPOGROSSI, MC AF GAMBASSI, G LAKATTA, EG CAPOGROSSI, MC TI ALPHA-1B-ADRENOCEPTOR DECREASES CYTOSOLIC PH VIA PROTEIN-KINASE-C MEDIATED INHIBITION OF NA+/H+ EXCHANGE SO CIRCULATION LA English DT Meeting Abstract C1 NIA,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. NR 0 TC 3 Z9 3 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 382 EP 382 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68202088 ER PT J AU PANZA, JA LAURIENZO, JM QUYYUMI, AA CANNON, RO AF PANZA, JA LAURIENZO, JM QUYYUMI, AA CANNON, RO TI TRANSESOPHAGEAL DOBUTAMINE STRESS ECHOCARDIOGRAPHY FOR EVALUATION OF CORONARY-ARTERY DISEASE SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 404 EP 404 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68202205 ER PT J AU RADE, JJ LEE, SW DICHEK, DA AF RADE, JJ LEE, SW DICHEK, DA TI VIRAL VECTOR-MEDIATED EXPRESSION OF BIOLOGICALLY-ACTIVE HIRUDIN IN CULTURED ENDOTHELIAL-CELLS SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 418 EP 418 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68202280 ER PT J AU DUVERGER, N KLEIN, HG LUC, G FRUCHART, JC ALBERS, JJ BREWER, HB SANTAMARINAFOJO, S AF DUVERGER, N KLEIN, HG LUC, G FRUCHART, JC ALBERS, JJ BREWER, HB SANTAMARINAFOJO, S TI IDENTIFICATION OF A NOVEL MUTATION IN THE LCAT GENE RESULTING IN FISH EYE DISEASE WITH ALPHA-LCAT ACTIVITY SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. PASTEUR INST,LILLE,FRANCE. UNIV WASHINGTON,SEATTLE,WA 98195. NR 0 TC 5 Z9 5 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 423 EP 423 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68202310 ER PT J AU KLEIN, HG DUVERGER, N MARCOVINA, S SANTAMARINAFOJO, S BREWER, HB AF KLEIN, HG DUVERGER, N MARCOVINA, S SANTAMARINAFOJO, S BREWER, HB TI LCAT DEFICIENCY - CHARACTERIZATION OF LCAT MUTATIONS WITH NORMAL PHOSPHOLIPASE BUT DEFECTIVE ENZYME-ACTIVITY SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. UNIV WASHINGTON,SEATTLE,WA 98195. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 423 EP 423 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68202311 ER PT J AU SINDLER, CJ SANTAMARINAFOJO, S TALLEY, G PARROT, C AF SINDLER, CJ SANTAMARINAFOJO, S TALLEY, G PARROT, C TI ANALYSIS OF THE CARBOXY-TERMINAL TETRAPEPTIDE OF APOLIPOPROTEIN-CII BY SITE-DIRECTED MUTAGENESIS SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,MDB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 462 EP 462 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68202519 ER PT J AU MUHLHAUSER, J JONES, M LEMARCHAND, P YAMADA, I CRYSTAL, RG CAPOGROSSI, MC AF MUHLHAUSER, J JONES, M LEMARCHAND, P YAMADA, I CRYSTAL, RG CAPOGROSSI, MC TI IN-VIVO GENE-TRANSFER INTO PORCINE CARDIAC-CELLS WITH A REPLICATION-DEFICIENT RECOMBINANT ADENOVIRUS VECTOR SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 475 EP 475 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68202591 ER PT J AU DAKAK, N QUYYUMI, AA EISENHOFER, G GOLDSTEIN, DS CANNON, RO AF DAKAK, N QUYYUMI, AA EISENHOFER, G GOLDSTEIN, DS CANNON, RO TI EFFECTS OF CARDIAC ALPHA-ADRENERGIC BLOCKADE ON CORONARY VASOMOTOR RESPONSES AND CARDIAC NOREPINEPHRINE KINETICS DURING MENTAL STRESS IN PATIENTS WITH CORONARY-ARTERY DISEASE SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 494 EP 494 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68202691 ER PT J AU BURCHFIEL, CM LAWS, A BENFANTE, R GOLDBERG, RJ HWANG, LJ CHIU, D RODRIGUEZ, BL CURB, JD SHARP, DS AF BURCHFIEL, CM LAWS, A BENFANTE, R GOLDBERG, RJ HWANG, LJ CHIU, D RODRIGUEZ, BL CURB, JD SHARP, DS TI JOINT EFFECTS OF HIGH-DENSITY-LIPOPROTEIN, TRIGLYCERIDE AND TOTAL CHOLESTEROL ON 18-YEAR RISK OF ATHEROSCLEROTIC DISEASE - THE HONOLULU HEART PROGRAM SO CIRCULATION LA English DT Meeting Abstract C1 NATL HEART LUNG & BLOOD INST,HONOLULU,HI. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 511 EP 511 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68202783 ER PT J AU CORDA, S ZIEGELSTEIN, RC SPURGEON, HA CAPOGROSSI, MC AF CORDA, S ZIEGELSTEIN, RC SPURGEON, HA CAPOGROSSI, MC TI THAPSIGARGIN MODULATES HUMAN AORTIC ENDOTHELIAL-CELL RESPONSE TO CAFFEINE SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 524 EP 524 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68202856 ER PT J AU SWEENEY, HL LANKFORD, E DANTZIG, J EPSTEIN, ND FANANAPAZIR, L AF SWEENEY, HL LANKFORD, E DANTZIG, J EPSTEIN, ND FANANAPAZIR, L TI ABNORMAL CONTRACTILE PROPERTIES OF MUSCLE-FIBERS EXPRESSING MUTATIONS IN BETA-MYOSIN THAT CAUSE HYPERTROPHIC CARDIOMYOPATHY SO CIRCULATION LA English DT Meeting Abstract C1 UNIV PENN,PHILADELPHIA,PA 19104. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 525 EP 525 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68202862 ER PT J AU XU, KY HANSFORD, RG ZWEIER, JL BECKER, LC AF XU, KY HANSFORD, RG ZWEIER, JL BECKER, LC TI FUNCTIONAL COUPLING OF GLYCOLYSIS WITH SARCOPLASMIC-RETICULUM CA2+ TRANSPORT SO CIRCULATION LA English DT Meeting Abstract C1 JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NIA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 526 EP 526 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68202867 ER PT J AU LIPSHULTZ, SE AF LIPSHULTZ, SE TI PROGRESSIVE LEFT-VENTRICULAR SYSTOLIC DYSFUNCTION IN HIV-INFECTED CHILDREN - THE PROSPECTIVE NHLBI P2C2 HIV STUDY SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 533 EP 533 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68202904 ER PT J AU MANOLIO, TA FURBERG, CD SISCOVICK, D BORHANI, NO NEWMAN, AB GARDIN, JM RAUTAHARJU, PM AF MANOLIO, TA FURBERG, CD SISCOVICK, D BORHANI, NO NEWMAN, AB GARDIN, JM RAUTAHARJU, PM TI DIURNAL-VARIATIONS AND CORRELATES OF ISCHEMIC EPISODES IN OLDER ADULTS - THE CARDIOVASCULAR HEALTH STUDY (CHS) SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 613 EP 613 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68203329 ER PT J AU SAVAGE, PJ PRESSEL, S CURB, D AF SAVAGE, PJ PRESSEL, S CURB, D TI INFLUENCE OF LOW-DOSE DIURETIC THERAPY ON GLUCOSE AND LIPID-LEVELS IN ELDERLY MEN AND WOMEN - THE SHEP STUDY SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 613 EP 613 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68203328 ER PT J AU CASINO, PR KILCOYNE, CM CANNON, RO GILLIGAN, DM QUYYUMI, AA PANZA, JA AF CASINO, PR KILCOYNE, CM CANNON, RO GILLIGAN, DM QUYYUMI, AA PANZA, JA TI IMPAIRED ENDOTHELIUM-DEPENDENT VASCULAR RELAXATION IN PATIENTS WITH HYPERCHOLESTEROLEMIA EXTENDS BEYOND THE MUSCARINIC RECEPTOR SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 618 EP 618 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68203357 ER PT J AU DAKAK, N GILLIGAN, DM ANDREWS, NP DIODATI, JG PANZA, JA SCHENKE, WH CANNON, RO QUYYUMI, AA AF DAKAK, N GILLIGAN, DM ANDREWS, NP DIODATI, JG PANZA, JA SCHENKE, WH CANNON, RO QUYYUMI, AA TI PERIPHERAL VASCULAR ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH MULTIPLE CORONARY RISK-FACTORS SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 618 EP 618 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68203356 ER PT J AU LEFROY, DC DELMONTE, F CRAKE, T HARDING, S POOLEWILSON, PA AF LEFROY, DC DELMONTE, F CRAKE, T HARDING, S POOLEWILSON, PA TI EFFECTS OF ANGIOTENSIN-II ON ATRIAL AND VENTRICULAR CARDIAC MYOCYTE CONTRACTION SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 631 EP 631 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68203425 ER PT J AU GE, SP JONES, M SHIOTA, T YAMADA, I VALDESCRUZ, L SAHN, DJ AF GE, SP JONES, M SHIOTA, T YAMADA, I VALDESCRUZ, L SAHN, DJ TI QUANTIFICATION OF FLOW AND EFFECTIVE ORIFICE SIZE FOR MITRAL BILEAFLET MECHANICAL VALVES - VALIDATION OF A NEW COLOR DOPPLER SEGMENT OF A SPHEROID FLOW CONVERGENCE METHOD IN AN ANIMAL-MODEL SO CIRCULATION LA English DT Meeting Abstract C1 OREGON HLTH SCI UNIV,PORTLAND,OR 97201. NHLBI,BETHESDA,MD 20892. MAIMONIDES HOSP,BROOKLYN,NY 11219. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 642 EP 642 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA682 UT WOS:A1993MA68203487 ER PT J AU LENFANT, C AF LENFANT, C TI WOMEN IN BIOMEDICAL SCIENCE - THROUGH THE LOOKING-GLASS SO CIRCULATION LA English DT Editorial Material RP LENFANT, C (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 1409 EP 1409 PN 1 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA678 UT WOS:A1993MA67800001 PM 8403285 ER PT J AU VAITKEVICIUS, PV FLEG, JL ENGEL, JH OCONNOR, FC WRIGHT, JG LAKATTA, LE YIN, FCP LAKATTA, EG AF VAITKEVICIUS, PV FLEG, JL ENGEL, JH OCONNOR, FC WRIGHT, JG LAKATTA, LE YIN, FCP LAKATTA, EG TI EFFECTS OF AGE AND AEROBIC CAPACITY ON ARTERIAL STIFFNESS IN HEALTHY-ADULTS SO CIRCULATION LA English DT Article DE AGING; EXERCISE ID AORTIC INPUT IMPEDANCE; LEFT-VENTRICULAR MASS; HEART-DISEASE; NONINVASIVE DETERMINATION; FRAMINGHAM; RISK; DISTENSIBILITY; POPULATION; EXERCISE; MEN AB Background. It has been well established that arterial stiffness, manifest as an increase in arterial pulse wave velocity or late systolic amplification of the carotid artery pressure pulse, increases with age. However, the populations studied in prior investigations were not rigorously screened to exclude clinical hypertension, occult coronary disease, or diabetes. Furthermore, it is unknown whether exercise capacity or chronic physical endurance training affects the age-associated increase in arterial stiffness. Methods and Results. Carotid arterial pressure pulse augmentation index (AGI), using applanation tonometry, and aortic pulse wave velocity (APWV) were measured in 146 male and female volunteers 21 to % years old from the Baltimore Longitudinal Study of Aging, who were rigorously screened to exclude clinical and occult cardiovascular disease. Aerobic capacity was determined in all individuals by measurement of maximal oxygen consumption (VO2max) during treadmill exercise. In this healthy, largely sedentary cohort, the arterial stiffness indexes AGI and APWV increased approximately fivefold and twofold, respectively, across the age span in both men and women, despite only a 14% increase in systolic blood pressure (SBP). These age-associated increases in AGI and APWV were of a similar magnitude to those in prior studies of less rigorously screened populations. Both AGI and APWV varied inversely with VO2max, and this relationship, at least for AGI, was independent of age. In endurance trained male athletes, 54 to 75 years old (VO2max=44+/-3 mL . kg-1 . min-1), the arterial stiffness indexes were significantly reduced relative to their sedentary age peers (AGI, 36% lower, APWV, 26% lower) despite similar blood pressures. Conclusions. Even in normotensive, rigorously screened volunteers in whom SBP increased an average of only 14% between ages 20 and 90 years, major age-associated increases of arterial stiffness occur. Higher physical conditioning status, indexed by VO2max, was associated with reduced arterial stiffness, both within this predominantly sedentary population and in endurance trained older men relative to their less active age peers. These findings suggest that interventions to improve aerobic capacity may mitigate the stiffening of the arterial tree that accompanies normative aging. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224. UNIV MARYLAND,SCH MED,DIV GERIATR MED,BALTIMORE,MD 21201. JOHNS HOPKINS UNIV,SCH MED,DIV CARDIOL,BALTIMORE,MD 21205. FU NIA NIH HHS [P0-1-AG-04402-9, 5T32AG00120-02] NR 28 TC 563 Z9 573 U1 2 U2 29 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 1456 EP 1462 PN 1 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA678 UT WOS:A1993MA67800008 PM 8403292 ER PT J AU TAYLOR, HA CHAITMAN, BR ROGERS, WJ KERN, MJ TERRIN, ML AGUIRRE, FV SOPKO, G MCMAHON, R ROSS, RN BOVILL, EC AF TAYLOR, HA CHAITMAN, BR ROGERS, WJ KERN, MJ TERRIN, ML AGUIRRE, FV SOPKO, G MCMAHON, R ROSS, RN BOVILL, EC TI RACE AND PROGNOSIS AFTER MYOCARDIAL-INFARCTION - RESULTS OF THE THROMBOLYSIS IN MYOCARDIAL-INFARCTION (TIMI) PHASE-II TRIAL SO CIRCULATION LA English DT Article DE RISK FACTORS; MYOCARDIAL INFARCTION; THROMBOLYSIS ID CORONARY HEART-DISEASE; NON-HISPANIC WHITES; PLASMINOGEN-ACTIVATOR; BLACK POPULATIONS; MORTALITY MORBIDITY; UNITED-STATES; MEDICAL-CARE; THERAPY; MANIFESTATIONS; AMERICANS AB Background. To better understand the role of race/ethnicity in survival after acute myocardial infarction, we compared clinical and laboratory data, response to thrombolytic therapy, and clinical outcome in 2885 patients participating in the Thrombolysis in Myocardial Infarction Phase II (TIMI II) Trial among three groups of patients (2564 whites, 174 blacks, and 147 Hispanics). Methods and Results. Differences were found in baseline characteristics among the three groups including (1) age (mean age for whites, 57.2 years; blacks, 54.8 years; Hispanics, 52.8 years; P<.001), (2) sex (percentage of women for whites, 17.6; blacks, 28.7; Hispanics, 14.3; P<.001), and (3) risk factor prevalence: current smoking (percent for whites, 49.4; blacks, 62.1; Hispanics, 55.1; P<.003), history of hypertension (percent for whites, 36.6; blacks, 55.7; Hispanics, 39.5; P<.001), and diabetes mellitus (percent for whites, 11.9; blacks, 22.4; Hispanics, 19.7; P<.001). Changes in hemostatic factors 5 hours after infusion of recombinant tissue plasminogen activator (rt-PA) revealed a more profound fall in fibrinogen levels in black patients compared with the response seen in Hispanic or white patients (mean change in fibrinogen +/- SD, mg/dL: 151.3 +/- 107.4, 112.2 +/- 97.0, 109.4 +/- 98.6; P <.001, respectively) without more frequent infarct-related artery patency or hemorrhagic complications. Mortality was similar in the white, black, and Hispanic patients through the first year after adjustment for baseline variables. Conclusions. TIMI II data yield evidence that (1) corroborates published reports of a high prevalence of classic cardiovascular risk factors among minority patients with acute myocardial infarction, (2) there is a greater decrease in fibrinogen levels 5 hours after the start of rt-PA infusion among black patients than in white and Hispanic patients without evidence of more frequent infarct-related artery patency or hemorrhagic complications, and (3) thrombolytic therapy with appropriate supplemental measures is associated with com arable 1-year mortalility in white, black, and Hispanic patients. C1 MARYLAND MED RES INST,TIMI COORDINATING CTR,600 WYNDHURST AVE,BALTIMORE,MD 21210. UNIV ALABAMA,BIRMINGHAM,AL 35294. ST LOUIS UNIV,ST LOUIS,MO 63103. NHLBI,BETHESDA,MD 20892. UNIV VERMONT,BURLINGTON,VT 05405. NR 31 TC 28 Z9 30 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 1484 EP 1494 PN 1 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA678 UT WOS:A1993MA67800012 PM 8403296 ER PT J AU MARINNETO, JA DILSIZIAN, V ARRIGHI, JA FREEDMAN, NMT PERRONEFILARDI, P BACHARACH, SL BONOW, RO AF MARINNETO, JA DILSIZIAN, V ARRIGHI, JA FREEDMAN, NMT PERRONEFILARDI, P BACHARACH, SL BONOW, RO TI THALLIUM REINJECTION DEMONSTRATES VIABLE MYOCARDIUM IN REGIONS WITH REVERSE REDISTRIBUTION SO CIRCULATION LA English DT Article DE MYOCARDIUM; THALLIUM; COLLATERAL CIRCULATION; CORONARY ARTERY DISEASE; POSITRON EMISSION TOMOGRAPHY ID CORONARY-ARTERY DISEASE; POSITRON-EMISSION TOMOGRAPHY; LEFT-VENTRICULAR DYSFUNCTION; NONVIABLE MYOCARDIUM; ISCHEMIC MYOCARDIUM; RABBIT MYOCARDIUM; BLOOD-FLOW; TL-201; INFARCTION; KINETICS AB Background. The clinical significance and pathophysiological mechanisms of reverse redistribution on stress-redistribution thallium-201 myocardial scintigraphy in patients with chronic coronary artery disease are unclear. Recent studies have shown that thallium-201 reinjection is a useful technique for the detection of myocardial viability in chronic coronary artery disease. In this investigation we determined whether thallium reinjection distinguishes viable from nonviable myocardium in regions with reverse redistribution. Methods and Results. We studied 39 patients with chronic stable coronary artery disease (age, 60+/-10 years), all of whom demonstrated reverse redistribution on standard exercise-redistribution thallium single-photon emission computed tomography (SPECT). Reverse redistribution was defined as greater-than-or-equal-to 10% decrease in relative thallium-201 activity between stress and redistribution images and included either the worsening of a perfusion defect apparent on post-stress images or the appearance of a new defect on the redistribution images. Thallium reinjection was performed immediately after the 3- to 4-hour redistribution study. Of 39 regions with reverse redistribution, 32 (82%) showed enhanced thallium-201 activity (greater-than-or-equal-to 10% increase) after reinjection. In the other 7 regions (18%), the scintigraphic defect persisted after reinjection. Abnormal Q waves were present in only 8 of 32 (25%) regions with enhanced thallium-201 uptake after reinjection compared with 5 of 7 (71%) regions not responding to reinjection (P<.05). Akinetic or dyskinetic wall motion was present in 3 of 32 (9%) regions showing enhanced uptake after reinjection, in contrast with 5 of 7 (71%) regions not responding to reinjection (P<.01). Critically stenosed or totally occluded coronary arteries supplied 24 of 29 (83%) regions with enhanced thallium-201 uptake after reinjection but only 2 of 7 (28%) regions not showing a positive response to reinjection (P<.05). Collateral circulation was detected in 23 of 29 (79%) regions with a positive thallium reinjection effect but in only 1 of the other 7 regions (P<.01). Sixteen of the 39 patients also underwent positron emission tomography using F-18-fluorodeoxyglucose (FDG) to assess glucose utilization and (H2O)-O-15 to assess regional blood flow. The 14 regions with reverse redistribution that responded to reinjection with enhanced thallium uptake all showed either normal patterns of FDG uptake and flow or an ischemic pattern with increased FDG uptake relative to flow. Reduced FDG uptake and reduced flow values were seen in the two regions not responding to thallium reinjection. Conclusions. These observations indicate that reverse redistribution in chronic coronary artery disease usually reflects viable myocardium, critically dependent upon collateral circulation. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NIH,DEPT NUCL MED,BETHESDA,MD 20892. NR 40 TC 41 Z9 42 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1993 VL 88 IS 4 BP 1736 EP 1745 PN 1 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MA678 UT WOS:A1993MA67800037 PM 8403320 ER PT J AU WEINSTEIN, LS SHENKER, A AF WEINSTEIN, LS SHENKER, A TI G-PROTEIN MUTATIONS IN HUMAN-DISEASE SO CLINICAL BIOCHEMISTRY LA English DT Article; Proceedings Paper CT 36TH ANNUAL CONF OF THE CANADIAN-SOC-OF-CLINICAL-CHEMISTS CY MAY 24-28, 1992 CL TORONTO, CANADA SP CANADIAN SOC CLIN CHEMISTS DE GUANINE NUCLEOTIDE REGULATORY PROTEIN; SIGNAL PATHWAYS; MCCUNE-ALBRIGHT SYNDROME; FIBROUS DYSPLASIA; POLYOSTOTIC; PSEUDOHYPOPARATHYROIDISM; ADENOSINE CYCLIC MONOPHOSPHATE; ADRENAL GLAND NEOPLASMS; ENDOCRINE DISEASES ID ALBRIGHT HEREDITARY OSTEODYSTROPHY; STIMULATORY G-PROTEIN; BETA-GAMMA-SUBUNITS; NUCLEOTIDE-BINDING PROTEIN; CYCLASE COUPLING PROTEIN; HUMAN PITUITARY-TUMORS; NIH 3T3 CELLS; ALPHA-SUBUNIT; ADENYLYL CYCLASE; CYCLIC-AMP AB The heterotrimeric G proteins couple cell-surface receptors for extracellular signals to intracellular effectors that generate second messengers. Abnormal G protein signalling, resulting from posttranslational modifications by bacterial toxins, altered gene expression, or gene mutations, may lead to diverse biological consequences. Mutations within G protein alpha subunit genes that lead to either constitutive activation or loss of function have been identified. Such G protein mutations play a role in the pathogenesis of several human diseases, including sporadic endocrine tumors, McCune-Albright syndrome, and Albright hereditary osteodystrophy. RP WEINSTEIN, LS (reprint author), NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BLDG 10,ROOM 8C101,BETHESDA,MD 20892, USA. RI Weinstein, Lee/I-5575-2015; OI Weinstein, Lee/0000-0002-1899-5152 NR 78 TC 43 Z9 43 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0009-9120 J9 CLIN BIOCHEM JI Clin. Biochem. PD OCT PY 1993 VL 26 IS 5 BP 333 EP 338 DI 10.1016/0009-9120(93)90109-J PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA ME856 UT WOS:A1993ME85600002 PM 8299203 ER PT J AU REINCKE, M ALLOLIO, B PETZKE, F HEPPNER, C MBULAMBERI, D VOLLMER, D WINKELMANN, W CHROUSOS, GP AF REINCKE, M ALLOLIO, B PETZKE, F HEPPNER, C MBULAMBERI, D VOLLMER, D WINKELMANN, W CHROUSOS, GP TI THYROID-DYSFUNCTION IN AFRICAN TRYPANOSOMIASIS - A POSSIBLE ROLE FOR INFLAMMATORY CYTOKINES SO CLINICAL ENDOCRINOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA-CACHECTIN; BRUCEI INFECTION; CENTRAL HYPOTHYROIDISM; CRITICAL ILLNESS; THYROTROPIN; PATHOGENESIS; LESIONS; HORMONE; SECRETION AB OBJECTIVE Sleeping sickness (African trypanosomiasis) is an anthropozoonosis transmitted by the tsetse fly. The treatments of choice are the antiparasitic agents suramin and/or melarsoprol. Experimental infection of animals with Trypanosoma brucei results in inflammatory lesions in the pituitary and/or the thyroid gland. In biochemical terms, these animals have hypothyroidism. We evaluated the functional integrity of the hypothalamic-pituitary-thyroid axis in patients with African trypanosomiasis before, during and after specific therapy. DESIGN Prospective, controlled, cross-sectional study. PATIENTS AND MEASUREMENTS Sixty-five patients with sleeping sickness (31 female, 34 male; aged 18-66; 32 with haemolymphatic sleeping sickness receiving suramin i.v., 33 with cerebral sleeping sickness receiving melarsoprol) and 13 control subjects (6 female, 7 male; aged 21-60) were enrolled in a cross-sectional study after giving informed consent. Fourteen patients were studied shortly, after admission for sleeping sickness, 19 in the middle of the course of treatment, 18 at the end of the 5-week treatment period, and 14 patients after cure. All subjects underwent a TRH stimulation test at 1200 with bolus injection of 400,ug TRH i.v. Blood was drawn for determination of fT3, fT4, TSH, rT3, TNF-alpha, IL-1 and IL-6 at 0 minutes and TSH at 60 minutes. All hormones and cytokines were determined by RIA or ELISA. RESULTS Baseline TSH concentrations (mean+/-SEM) were elevated in unmedicated patients with sleeping sickness compared to normal subjects (2.6+/-0.4 vs 1.4+/-0.2 mU/l; P = 0.01), whereas fT3 (2.7+/-0.5 vs 5.8+/-0.3 pmol/l; P 0.0002) and fT4 concentrations (10.3+/-1.2 vs 15.4+0.8 pmol/l; P = 0.007) were low. Stimulated TSH concentrations did not significantly differ from normal controls. Reverse T3 concentration in patients with sleeping sickness were normal (2.2 +/- 0.3 vs 2.4 +/- 0.2 nmol/l; P = NS). During the course of treatment, baseline TSH, fT3 and fT4 concentrations slowly returned to normal and were indistinguishable from controls after cure. Plasma concentrations of TNF-alpha (16.0+/-4.1 vs 2.9+/-1.4 ng/l in controls; P = 0.003) and interleukin-6 (19.2+/-7.3 vs 1.3+/-0.2 ng/l; P = 0.0001), but not interleukin-1beta (2.0+/-0.2 vs 0.9+/-0.2, ng/l P = NS), were elevated, when thyroid function impairment and disease activity were al their maximum, but gradually decreased into the normal range with therapy. We found a negative correlation between baseline cytokine concentrations and fT3 concentrations (TNF-alpha: r = -0.34, P = 0.003; IL-6: r = -0.43, P = 0.0001). CONCLUSIONS We conclude that unmedicated sleeping sickness is associated with significant impairment of thyroid function, which is reversed with specific therapy. Elevated TSH concentrations and low fT3 and fT4 concentrations suggest primary hypothyroidism in patients with sleeping sickness. However, an additional pituitary and/or hypothalamic component cannot be excluded. This impairment may be due to the elevated plasma cytokine concentrations found in these patients or may be the result of parasitic thyroiditis. C1 UNIV COLOGNE, DEPT MED 2, W-5000 COLOGNE 41, GERMANY. NATL SLEEPING SICKNESS CONTROL PROGRAM, JINJA, UGANDA. NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. RP REINCKE, M (reprint author), UNIV WURZBURG, MED KLIN, JOSEF SCHNEIDER STR 2, W-8700 WURZBURG, GERMANY. NR 38 TC 18 Z9 18 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD OCT PY 1993 VL 39 IS 4 BP 455 EP 461 DI 10.1111/j.1365-2265.1993.tb02393.x PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MA088 UT WOS:A1993MA08800011 PM 8287572 ER PT J AU HARIGAI, M HARA, M YOSHIMURA, T LEONARD, EJ INOUE, K KASHIWAZAKI, S AF HARIGAI, M HARA, M YOSHIMURA, T LEONARD, EJ INOUE, K KASHIWAZAKI, S TI MONOCYTE CHEMOATTRACTANT PROTEIN-1 (MCP-1) IN INFLAMMATORY JOINT DISEASES AND ITS INVOLVEMENT IN THE CYTOKINE NETWORK OF RHEUMATOID SYNOVIUM SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article ID TUMOR NECROSIS FACTOR; GENE JE; ARTHRITIS; CELLS; INTERLEUKIN-1; EXPRESSION; FIBROBLASTS; FLUID; SERUM C1 NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,IMMUNOPATHOL SECT,BETHESDA,MD 20892. RP HARIGAI, M (reprint author), TOKYO WOMENS MED COLL,INST RHEUMATOL,KS BLDG,9-12 WAKAMATSU CHO,SHINJUKU KU,TOKYO 162,JAPAN. NR 24 TC 112 Z9 113 U1 0 U2 7 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD OCT PY 1993 VL 69 IS 1 BP 83 EP 91 DI 10.1006/clin.1993.1153 PG 9 WC Immunology; Pathology SC Immunology; Pathology GA MA656 UT WOS:A1993MA65600012 PM 8403545 ER PT J AU MOXEYMIMS, MM FRANK, MM LIN, EY FRANCIS, C GAITHER, TA AF MOXEYMIMS, MM FRANK, MM LIN, EY FRANCIS, C GAITHER, TA TI INCREASED EXPRESSION OF FC-GAMMA-RI ON ISOLATED PMN FROM INDIVIDUALS OF AFRICAN DESCENT SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Note ID HIGH-AFFINITY RECEPTOR; POLYMORPHONUCLEAR LEUKOCYTES; IGG; PHAGOCYTOSIS; MONOCYTES; NEUTROPHILS; GRANULOCYTES; NUMBER; INVIVO; CELLS RP MOXEYMIMS, MM (reprint author), NIAID,CLIN INVEST LAB,BETHESDA,MD 20892, USA. NR 28 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 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD OCT PY 1993 VL 69 IS 1 BP 117 EP 121 DI 10.1006/clin.1993.1158 PG 5 WC Immunology; Pathology SC Immunology; Pathology GA MA656 UT WOS:A1993MA65600017 PM 8403539 ER PT J AU GAYDOS, CA FOWLER, CL GILL, VJ EIDEN, JJ QUINN, TC AF GAYDOS, CA FOWLER, CL GILL, VJ EIDEN, JJ QUINN, TC TI DETECTION OF CHLAMYDIA-PNEUMONIAE BY POLYMERASE CHAIN REACTION-ENZYME IMMUNOASSAY IN AN IMMUNOCOMPROMISED POPULATION SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID STRAIN TWAR; INFECTION; DISEASE; ASSOCIATION; EPIDEMICS AB Chlamydia pneumoniae has now been associated with pneumonia, bronchitis, pharyngitis, acute chest syndrome of sickle cell disease, and asthma. Because of the difficulty of primary isolation and tissue-culture adaptation of this organism, we used a previously developed polymerase chain reaction-enzyme immunoassay (PCR-EIA) to screen 132 culture-negative bronchoalveolar lavage (BAL) specimens from 108 immunocompromised patients (34% of whom were positive for human immunodeficiency virus) and 7 healthy volunteers. Thirteen specimens (9.8%) from 12 immunocompromised patients (11.1%) gave a positive result; one patient had two positive specimens obtained 3 days apart. No healthy volunteer had a PCR-EIA-positive BAL specimen. Twelve (11.1%) of the immunocompromised patients also had diagnostic levels of antibody. Four patients had positive results in both PCR-EIA and serological tests. Thus 20 (18.5%) of the 108 patients had laboratory evidence of C. pneumoniae infection. These data indicate that diagnosis of acute infection with C. pneumoniae can be established more rapidly and reliably by PCR-EIA than by culture or serology, particularly among immunocompromised patients, in whom serological changes in response to infection are relatively undependable. With an infection rate of 11.1% according to PCR-EIA, C. pneumoniae should be considered in the evaluation and treatment of pneumonia in immunocompromised patients. C1 JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,ROSS RES BLDG 1159,720 RUTLAND AVE,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DIV PEDIAT INFECT DIS,BALTIMORE,MD 21205. NIAID,CTR CLIN,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RI Gaydos, Charlotte/E-9937-2010 NR 29 TC 58 Z9 58 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT PY 1993 VL 17 IS 4 BP 718 EP 723 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA MA709 UT WOS:A1993MA70900019 PM 8268355 ER PT J AU WANG, RYH SHIH, JWK WEISS, SH GRANDINETTI, T PIERCE, PF LANGE, M ALTER, HJ WEAR, DJ DAVIES, CL MAYUR, RK LO, SC AF WANG, RYH SHIH, JWK WEISS, SH GRANDINETTI, T PIERCE, PF LANGE, M ALTER, HJ WEAR, DJ DAVIES, CL MAYUR, RK LO, SC TI MYCOPLASMA-PENETRANS INFECTION IN MALE-HOMOSEXUALS WITH AIDS - HIGH SEROPREVALENCE AND ASSOCIATION WITH KAPOSIS-SARCOMA SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID UROGENITAL TRACT; SP-NOV; MEN; CELLS; EPIDEMIOLOGY; GENITALIUM; COHORT; URETHRITIS; COFACTORS; IL-1 AB Antibodies to Mycoplasma penetrans were found at an unusually high frequency in male homosexuals with AIDS (55 of 149; 37%) and in human immunodeficiency virus (HIV)-infected asymptomatic homosexuals (13 of 49; 26.5%) but not in intravenous drug users (3 of 308; 1%) and hemophiliacs (1 of 165; 0.6%) with or without HIV-1 infection. Thus, both M. penetrans and Kaposi's sarcoma (KS) occur primarily in male homosexuals and rarely in other groups of patients at high risk of AIDS. Among 414 HIV-1-infected patients, statistical analysis revealed those with M. penetrans antibody were 11.7 times more likely to develop KS. Furthermore, among 198 HIV-infected homosexuals (149 with AIDS and 49 without AIDS), those with KS had M. penetrans-specific antibody at a significantly higher frequency (28 of 47; 59.6%) than did those without KS (27 of 102 with AIDS [26.5%] as well as 13 of 49 without AIDS [26.5%]; odds ratio = 4.1, P < .001). M. penetrans is apparently transmitted sexually through homosexual activity and is epidemiologically linked to formation of KS in homosexual men with AIDS. Parallel tests with M. genitalium revealed no similar link to KS in the same study sample. C1 ARMED FORCES INST PATHOL,DEPT INFECT & PARASIT DIS PATHOL,DIV MOLEC PATHOBIOL,BLDG 54,WASHINGTON,DC 20306. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,DEPT PREVENT MED & COMMUNITY HLTH,NEWARK,NJ 07103. NATL CAPITAL CHAPTER,AMER RED CROSS,WASHINGTON,DC. GEORGETOWN UNIV HOSP,HIV CLIN PROGRAM,WASHINGTON,DC 20007. ST LUKES ROOSEVELT HOSP,DIV INFECT DIS & EPIDEMIOL,NEW YORK,NY 10025. FU NIAID NIH HHS [NIAID AI-31830] NR 44 TC 73 Z9 78 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT PY 1993 VL 17 IS 4 BP 724 EP 729 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA MA709 UT WOS:A1993MA70900020 PM 8268356 ER PT J AU STEIN, DS TIMPONE, JG GRADON, JD KAGAN, JM SCHNITTMAN, SM AF STEIN, DS TIMPONE, JG GRADON, JD KAGAN, JM SCHNITTMAN, SM TI IMMUNE-BASED THERAPEUTICS - SCIENTIFIC RATIONALE AND THE PROMISING APPROACHES TO THE TREATMENT OF THE HUMAN-IMMUNODEFICIENCY-VIRUS INFECTED INDIVIDUAL SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID TUMOR-NECROSIS-FACTOR; AIDS-RELATED COMPLEX; T-CELL CLONES; BONE-MARROW TRANSPLANTATION; PLACEBO-CONTROLLED TRIAL; BLOOD MONONUCLEAR-CELLS; CYTOTOXIC LYMPHOCYTES-T; RECOMBINANT INTERFERON-ALPHA; DEFICIENCY SYNDROME AIDS; LEUKOCYTE-A INTERFERON AB The primary approach to therapy for infection with human immunodeficiency virus (HIV) continues to be centered around antiretroviral agents that have conferred significant clinical benefits. The considerable degree of immunologic dysfunction in HIV infection, however, has led to intense interest in methods of immune stimulation and reconstitution. Immunomodulatory intervention in HIV infection is highly controversial. Over the years a number of immunomodulatory agents-many with only a poor rationale for their clinical use-have been evaluated. In this review we concentrate on immunomodulatory approaches that are currently being investigated. We group these interventions, reviewing the rationale and clinical data for each category: passive immunity (administration of immunoglobulins and use of apheresis), thymic hormone treatment, cytokine treatment (administration of interleukins, tumor necrosis factor, and interferons), adoptive cellular immunity, and therapeutic vaccination. At present, the only interventions supported by data from well-controlled studies are the parenteral administration of interferon alpha to patients with HIV-associated Kaposi's sarcoma and the administration of pooled immunoglobulin (to decrease the rate of bacterial infections) to children who cannot take trimethoprim-sulfamethoxazole. However, several other approaches under development show promise in reversing some of the immune deficits of HIV infection. Clinical evaluation of these approaches should yield valuable insights into the immunopathogenesis of HIV infection, and these insights should facilitate the formulation of new modalities of treatment. C1 NIAID,DIV AIDS,CLIN RES PROGRAM,MED BRANCH,6003 EXECUT BLVD,ROCKVILLE,MD 20892. NR 195 TC 26 Z9 26 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT PY 1993 VL 17 IS 4 BP 749 EP 771 PG 23 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA MA709 UT WOS:A1993MA70900024 PM 8268360 ER PT J AU KING, DA CAINE, ED COX, C AF KING, DA CAINE, ED COX, C TI INFLUENCE OF DEPRESSION AND AGE ON SELECTED COGNITIVE FUNCTIONS SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article ID MAJOR DEPRESSION; DEMENTIA; DYSFUNCTION; INPATIENTS AB In order to test for possible interaction between the effects of age and the effects of depression, 45 patients with unipolar major depression and 118 normal controls ranging in age from 23 to 87 years completed tests of language, verbal and visual memory, copying, and complex psychomotor function. Biphasic regression analyses suggested more accelerated declines with age in the depressed group on tests of naming and complex psychomotor function. However, there were parallel age effects in depressives and controls on tests of verbal and visual memory, and copying. These results are discussed in terms of cognitive and neurobiologic processes that may underlie an interactive relationship between the effects of depression and the effects of age. C1 UNIV ROCHESTER,SCH MED & DENT,NIMH,DEPT BIOSTAT,CLIN RES CTR STUDY PSYCHOPATHOL ELDERLY,ROCHESTER,NY 14642. UNIV ROCHESTER,SCH MED & DENT,DEPT PSYCHIAT,ROCHESTER,NY 14642. NR 36 TC 16 Z9 16 U1 1 U2 2 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0920-1637 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD OCT PY 1993 VL 7 IS 4 BP 443 EP 453 DI 10.1080/13854049308401534 PG 11 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA ML701 UT WOS:A1993ML70100004 ER PT J AU BAGDADE, J RITTER, M NAGI, D KNOWLER, W AF BAGDADE, J RITTER, M NAGI, D KNOWLER, W TI ALTERED CHOLESTERYL ESTER TRAFFICKING MAY REDUCE CORONARY HEART-DISEASE (CHD) RISK IN PIMA-INDIANS WITH NONINSULIN-DEPENDENT DIABETES-MELLITUS (NIDDM) SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 NIH,PHOENIX,AZ. RUSH MED COLL,CHICAGO,IL 60612. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD OCT PY 1993 VL 41 IS 3 BP A692 EP A692 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LY017 UT WOS:A1993LY01700541 ER PT J AU BAGDADE, J RITTER, M NAGI, D KNOWLER, W AF BAGDADE, J RITTER, M NAGI, D KNOWLER, W TI DOES ABERRANT PLASMA TRAFFICKING OF CHOLESTERYL ESTER EXPLAIN THE IMMUNITY OF PIMA-INDIANS TO CORONARY HEART-DISEASE (CHD) SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 RUSH MED COLL,CHICAGO,IL 60612. NIH,PHOENIX,AZ. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD OCT PY 1993 VL 41 IS 3 BP A657 EP A657 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LY017 UT WOS:A1993LY01700353 ER PT J AU BARKSDALE, S PERNICIARO, C HALLING, K STRICKLER, JG AF BARKSDALE, S PERNICIARO, C HALLING, K STRICKLER, JG TI GRANULOMA-ANNULARE IN PATIENTS WITH MALIGNANT-LYMPHOMA SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD OCT PY 1993 VL 41 IS 3 BP A608 EP A608 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LY017 UT WOS:A1993LY01700090 ER PT J AU DICHTER, J SHELHAMER, JH OGNIBENE, FP AF DICHTER, J SHELHAMER, JH OGNIBENE, FP TI YIELD OF REPEAT BRONCHOSCOPY (FOB) MAY BE DEPENDENT ON UNDERLYING DISEASE SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 NIH,CC,DEPT CRIT CARE MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD OCT PY 1993 VL 41 IS 3 BP A593 EP A593 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LY017 UT WOS:A1993LY01700006 ER PT J AU HAY, JG CRYSTAL, RG AF HAY, JG CRYSTAL, RG TI HIGH-LEVEL AIRWAY SPECIFIC EXPRESSION AND CHROMOSOMAL SUB-LOCALIZATION OF THE HUMAN CC10 GENE SUGGEST A POTENTIAL ROLE IN ASTHMA SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 NHLBI,PULM BRANCH,BETHESDA,MD 20892. CORNELL UNIV,MED CTR,COLL MED,NEW YORK,NY 10021. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD OCT PY 1993 VL 41 IS 3 BP A593 EP A593 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LY017 UT WOS:A1993LY01700007 ER PT J AU HONE, J ACCILI, D SINCLAIR, L TAYLOR, SI AF HONE, J ACCILI, D SINCLAIR, L TAYLOR, SI TI HOMOZYGOSITY FOR A NULL ALLELE OF THE INSULIN-RECEPTOR GENE IN A PATIENT WITH LEPRECHAUNISM SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 NIDDK,DIABET BRANCH,BETHESDA,MD. WESTMINSTER MED SCH & HOSP,LONDON,ENGLAND. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD OCT PY 1993 VL 41 IS 3 BP A599 EP A599 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LY017 UT WOS:A1993LY01700041 ER PT J AU JOHNSON, MR DECLUE, JE FELZMANN, S VASS, WC XU, GF WHITE, R LOWY, DR AF JOHNSON, MR DECLUE, JE FELZMANN, S VASS, WC XU, GF WHITE, R LOWY, DR TI NEUROFIBROMIN CAN INHIBIT RAS-DEPENDENT GROWTH BY A MECHANISM INDEPENDENT OF ITS GTPASE ACCELERATING FUNCTION SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. UNIV UTAH,HOWARD HUGHES MED INST,SALT LAKE CITY,UT 84112. UNIV UTAH,DEPT HUMAN GENET,SALT LAKE CITY,UT 84112. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD OCT PY 1993 VL 41 IS 3 BP A607 EP A607 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LY017 UT WOS:A1993LY01700083 ER PT J AU MARTINEZ, A KOVACS, JA AF MARTINEZ, A KOVACS, JA TI EVALUATION OF RO11-8958, A NEW DIHYDROFOLATE-REDUCTASE INHIBITOR, IN THE TREATMENT OF ACUTE TOXOPLASMA INFECTION IN MICE SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD OCT PY 1993 VL 41 IS 3 BP A603 EP A603 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LY017 UT WOS:A1993LY01700061 ER PT J AU MASTRANGELI, A OCONNELL, B ALADIB, W NAGLER, R FOX, PC BAUM, BJ CRYSTAL, RG AF MASTRANGELI, A OCONNELL, B ALADIB, W NAGLER, R FOX, PC BAUM, BJ CRYSTAL, RG TI DIRECT IN-VIVO ADENOVIRUS-MEDIATED GENE-TRANSFER TO THE SALIVARY-GLANDS SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 NHLBI,PULM BRANCH,BETHESDA,MD 20892. NIDR,CIPCB,BETHESDA,MD 20892. CORNELL UNIV,MED CTR,COLL MED,NEW YORK,NY 10021. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD OCT PY 1993 VL 41 IS 3 BP A614 EP A614 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LY017 UT WOS:A1993LY01700120 ER PT J AU TSIGOS, C ARAI, K HUNG, W CHROUSOS, GP AF TSIGOS, C ARAI, K HUNG, W CHROUSOS, GP TI ISOLATED GLUCOCORTICOID DEFICIENCY (ACTH RESISTANCE) ASSOCIATED WITH ABNORMALITIES OF THE ACTH RECEPTOR GENE SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD OCT PY 1993 VL 41 IS 3 BP A600 EP A600 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LY017 UT WOS:A1993LY01700044 ER PT J AU EICHHORN, GL AF EICHHORN, GL TI CONFORMATIONAL CHANGE INDUCED BY METAL-IONS THROUGH COORDINATION SO COORDINATION CHEMISTRY REVIEWS LA English DT Review ID DNA AB The structure of a metal complex may be determined by the structure of the ligand or by the electronic configuration of the metal. In the latter case, the metal can induce a conformational change in the ligand. Such a conformational change is a usual result in coordination reactions, and is particularly significant in biological macromolecules, such as nucleic acids, proteins, and enzymes. We have recently obtained evidence for a mechanism that involves a metal participating in conformational changes that occur in both enzyme and substrate simultaneously. RP EICHHORN, GL (reprint author), NIA,GERONTOL RES CTR,CELLULAR & MOLEC BIOL LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 20 TC 17 Z9 17 U1 2 U2 3 PU ELSEVIER SCIENCE SA LAUSANNE PI LAUSANNE 1 PA PO BOX 564, 1001 LAUSANNE 1, SWITZERLAND SN 0010-8545 J9 COORDIN CHEM REV JI Coord. Chem. Rev. PD OCT PY 1993 VL 128 IS 1-2 BP 167 EP 173 DI 10.1016/0010-8545(93)80028-4 PG 7 WC Chemistry, Inorganic & Nuclear SC Chemistry GA MD906 UT WOS:A1993MD90600007 ER PT J AU ETTINGER, WH HARRIS, T AF ETTINGER, WH HARRIS, T TI CAUSES OF HYPOCHOLESTEROLEMIA SO CORONARY ARTERY DISEASE LA English DT Article DE HYPOCHOLESTEROLEMIA; NUTRITION; INFLAMMATION ID FACTOR INTERVENTION TRIAL; TUMOR-NECROSIS-FACTOR; SERUM-CHOLESTEROL LEVELS; CORONARY HEART-DISEASE; LIPOPROTEIN CHOLESTEROL; PROGNOSTIC-SIGNIFICANCE; CYNOMOLGUS MONKEYS; MORTALITY; CANCER; LIPIDS C1 NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT INTERNAL MED,WINSTON SALEM,NC 27103. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. NR 62 TC 31 Z9 32 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0954-6928 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD OCT PY 1993 VL 4 IS 10 BP 854 EP 859 DI 10.1097/00019501-199310000-00003 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA MK599 UT WOS:A1993MK59900003 PM 8269190 ER PT J AU SHARRETT, AR AF SHARRETT, AR TI SERUM-CHOLESTEROL LEVELS AND ATHEROSCLEROSIS SO CORONARY ARTERY DISEASE LA English DT Article DE ARTERIOSCLEROSIS; CHOLESTEROL ID CORONARY-ARTERY DISEASE; INTIMA-MEDIA THICKNESS; COMMON CAROTID-ARTERY; RISK-FACTORS; FAMILIAL HYPERCHOLESTEROLEMIA; WALL THICKNESS; HEART-DISEASE; LIPOPROTEINS; ULTRASOUND; PATHOGENESIS RP SHARRETT, AR (reprint author), NHLBI,FED BLDG,ROOM 2C08,BETHESDA,MD 20892, USA. NR 32 TC 4 Z9 4 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0954-6928 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD OCT PY 1993 VL 4 IS 10 BP 867 EP 870 DI 10.1097/00019501-199310000-00005 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA MK599 UT WOS:A1993MK59900005 PM 8269192 ER PT J AU LOE, H AF LOE, H TI CHANGE IS ON THE WAY SO CRANIO-THE JOURNAL OF CRANIOMANDIBULAR PRACTICE LA English DT Editorial Material RP LOE, H (reprint author), NIDA,BETHESDA,MD 20205, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHROMA INC PI CHATTANOOGA PA 5323 BRAINERD RD, SUITE 106, CHATTANOOGA, TN 37411 SN 0886-9634 J9 CRANIO JI Cranio-J. Craniomandib. Pract. PD OCT PY 1993 VL 11 IS 4 BP 245 EP 246 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA MD999 UT WOS:A1993MD99900001 PM 8118893 ER PT J AU CHESEBRO, B CAUGHEY, B AF CHESEBRO, B CAUGHEY, B TI SCRAPIE AGENT REPLICATION WITHOUT THE PRION PROTEIN SO CURRENT BIOLOGY LA English DT Note ID PRP; IDENTIFICATION; FIBRILS; BRAIN; FORM RP CHESEBRO, B (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840, USA. NR 18 TC 16 Z9 16 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD OCT 1 PY 1993 VL 3 IS 10 BP 696 EP 698 DI 10.1016/0960-9822(93)90072-V PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MR821 UT WOS:A1993MR82100012 PM 15335865 ER PT J AU Gumbiner, BM Yamada, KM AF Gumbiner, Barry M. Yamada, Kenneth M. TI Cell-to-cell contact and extracellular matrix SO CURRENT OPINION IN CELL BIOLOGY LA English DT Editorial Material C1 [Gumbiner, Barry M.] Mem Sloan Kettering Canc Ctr, Cellular Biochem & Biophys Program, New York, NY 10021 USA. [Yamada, Kenneth M.] NIDR, Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gumbiner, BM (reprint author), Mem Sloan Kettering Canc Ctr, Cellular Biochem & Biophys Program, 1275 York Ave,Box 564, New York, NY 10021 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD OCT PY 1993 VL 5 IS 5 BP 769 EP 771 DI 10.1016/0955-0674(93)90023-J PG 3 WC Cell Biology SC Cell Biology GA V26EB UT WOS:000208527800001 ER PT J AU Kleiner, DE Stevenson, WGS AF Kleiner, David E., Jr. Stevenson, William G. Stetler TI Structural biochemistry and activation of matrix metalloproteases SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article AB The degradation of the extracellular matrix is part of many pathological and physiological processes. Of the several proteases involved in extracellular matrix turnover, the plasmin/plasminogen activator system and the family of matrix metalloproteases have received the most attention. Recent investigations in the field of matrix metalloprotease biochemistry have focused on the functions of the various enzyme domains and their interactions with inhibitor domains. Research into physiological activation mechanisms has demonstrated a plasmin/plasminogen activator-metalloprotease cascade, as well as providing an initial characterization of cell surface associated metalloprotease activation. C1 [Kleiner, David E., Jr.; Stevenson, William G. Stetler] NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Kleiner, DE (reprint author), NCI, Pathol Lab, Bldg 10,Room 2A33,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Stetler-Stevenson, William/H-6956-2012; OI Stetler-Stevenson, William/0000-0002-5500-5808; Kleiner, David/0000-0003-3442-4453 NR 45 TC 305 Z9 312 U1 0 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD OCT PY 1993 VL 5 IS 5 BP 891 EP 897 DI 10.1016/0955-0674(93)90040-W PG 7 WC Cell Biology SC Cell Biology GA V26EB UT WOS:000208527800018 PM 8240832 ER PT J AU PASS, HI POGREBNIAK, HW AF PASS, HI POGREBNIAK, HW TI MALIGNANT PLEURAL MESOTHELIOMA - FOREWORD SO CURRENT PROBLEMS IN SURGERY LA English DT Review ID CELL-LINES; EXTRAPLEURAL PNEUMONECTOMY; COMPUTED-TOMOGRAPHY; GROWTH-FACTOR; MONOCLONAL-ANTIBODY; ASBESTOS FIBERS; LUNG-CANCER; DIFFERENTIAL-DIAGNOSIS; DIFFUSE MESOTHELIOMA; PHOTODYNAMIC THERAPY RP PASS, HI (reprint author), NCI,THORAC ONCOL SECT,SURG BRANCH,BETHESDA,MD 20892, USA. NR 201 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 0011-3840 J9 CURR PROB SURG JI Curr. Probl. Surg. PD OCT PY 1993 VL 30 IS 10 BP 925 EP 1012 PG 88 WC Surgery SC Surgery GA MC746 UT WOS:A1993MC74600001 ER PT J AU KAGAN, JM MAYALL, BH AF KAGAN, JM MAYALL, BH TI INTRODUCTION TO THE NIAID GUIDELINE FOR FLOW CYTOMETRIC IMMUNOPHENOTYPING SO CYTOMETRY LA English DT Editorial Material C1 UNIV CALIF SAN FRANCISCO,DEPT LAB MED,SAN FRANCISCO,CA 94143. RP KAGAN, JM (reprint author), NIAID,DIV AIDS,BETHESDA,MD 20892, USA. NR 0 TC 4 Z9 4 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 0196-4763 J9 CYTOMETRY JI Cytometry PD OCT PY 1993 VL 14 IS 7 BP 701 EP 701 DI 10.1002/cyto.990140702 PG 1 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LX792 UT WOS:A1993LX79200001 ER PT J AU CALVELLI, T DENNY, TN PAXTON, H GELMAN, R KAGAN, J AF CALVELLI, T DENNY, TN PAXTON, H GELMAN, R KAGAN, J TI GUIDELINE FOR FLOW CYTOMETRIC IMMUNOPHENOTYPING - A REPORT FROM THE NATIONAL-INSTITUTE-OF-ALLERGY-AND-INFECTIOUS-DISEASES, DIVISION OF AIDS SO CYTOMETRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; QUALITY-CONTROL; T-CELL; TRANSFUSION SAFETY; HOMOSEXUAL MEN; HIV-INFECTION; LYMPHOCYTE; MULTICENTER; SUBSETS; PROGRAM C1 MARYLAND MED RES INST,DEPT FLOW CYTOMETRY,BALTIMORE,MD. UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,CHILDRENS HOSP,DEPT PEDIAT,NEWARK,NJ 07103. NIAID,DIV AIDS,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. RP CALVELLI, T (reprint author), YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT PEDIAT,BRONX,NY 10461, USA. OI Denny, Thomas/0000-0002-7364-8276 NR 39 TC 178 Z9 179 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 0196-4763 J9 CYTOMETRY JI Cytometry PD OCT PY 1993 VL 14 IS 7 BP 702 EP 715 DI 10.1002/cyto.990140703 PG 14 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LX792 UT WOS:A1993LX79200002 PM 8243200 ER PT J AU MOENS, CB STANTON, BR PARADA, LF ROSSANT, J AF MOENS, CB STANTON, BR PARADA, LF ROSSANT, J TI DEFECTS IN HEART AND LUNG DEVELOPMENT IN COMPOUND HETEROZYGOTES FOR 2 DIFFERENT TARGETED MUTATIONS AT THE N-MYC LOCUS SO DEVELOPMENT LA English DT Article DE N-MYC; HEART DEVELOPMENT; TARGETED MUTAGENESIS; MOUSE MUTANT ID C-MYC; DNA-BINDING; TRANSGENIC MICE; HOMOLOGOUS RECOMBINATION; EMBRYONIC LETHALITY; CELL-LINES; EXPRESSION; GENE; MOUSE; MAX AB Two types of mutant allele, one leaky and one null, have been generated by gene targeting at the N-myc locus in embryonic stem cells and the phenotypes of mice homozygous for these mutations have been described. These mutations have shown that N-myc has a number of functions during development, including a role in branching morphogenesis in the lung, which manifests itself at birth in mice homozygous for the leaky allele, and roles in the development of the mesonephric tubules, the neuroepithelium, the sensory ganglia, the gut and the heart, which become evident at midgestation in embryos homozygous for the null allele. In an attempt to define roles for N-myc at other stages of development, we have combined the two types of N-myc mutant allele in a compound heterozygote that as a result contains approximately 15% of normal levels of N-Myc protein. Compound heterozygotes died during gestation at a time intermediate to the times of death of embryos homozygous for either mutation individually, and their death appeared to result from cardiac failure stemming from hypoplasia of the compact subepicardial layer of the myocardium. Investigation of the expression pattern of N-myc and various markers of differentiation in wild-type and compound heterozygote mutant hearts has suggested that N-myc may function in maintaining the proliferation and/or preventing the differentiation of compact layer myocytes. This study illustrates the importance of generating different mutations at a given locus to elucidate fully the function of a particular gene during development. C1 SAMUEL LUNENFELD RES INST,DIV MOLEC & DEV BIOL,600 UNIV AVE,TORONTO M5G 1X5,ON,CANADA. NCI,FREDERICK CANC RES & DEV CTR,MOLEC EMBRYOL SECT,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. UNIV TORONTO,DEPT MOLEC & MED GENET,TORONTO M5S 1A1,ONTARIO,CANADA. RI Parada, luis/B-9400-2014; OI Moens, Cecilia/0000-0002-1099-0728 FU NCI NIH HHS [NCI-NO1-CO-74101] NR 61 TC 151 Z9 152 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD OCT PY 1993 VL 119 IS 2 BP 485 EP 499 PG 15 WC Developmental Biology SC Developmental Biology GA MB892 UT WOS:A1993MB89200014 PM 8287798 ER PT J AU REBAGLIATI, MR DAWID, IB AF REBAGLIATI, MR DAWID, IB TI EXPRESSION OF ACTIVIN TRANSCRIPTS IN FOLLICLE CELLS AND OOCYTES OF XENOPUS-LAEVIS SO DEVELOPMENTAL BIOLOGY LA English DT Article ID ERYTHROID-DIFFERENTIATION FACTOR; MESODERM INDUCTION; TGF-BETA; EGGS; EMBRYOS; IDENTIFICATION; SPECIFICATION; ROTATION; CLONING; STEP RP REBAGLIATI, MR (reprint author), NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892, USA. NR 40 TC 30 Z9 30 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD OCT PY 1993 VL 159 IS 2 BP 574 EP 580 DI 10.1006/dbio.1993.1265 PG 7 WC Developmental Biology SC Developmental Biology GA MC177 UT WOS:A1993MC17700017 PM 8405680 ER PT J AU SHIMAKAWA, T HERRERAACENA, MG COLDITZ, GA MANSON, JE STAMPER, MJ WILLETT, WC AF SHIMAKAWA, T HERRERAACENA, MG COLDITZ, GA MANSON, JE STAMPER, MJ WILLETT, WC TI COMPARISON OF DIETS OF DIABETIC AND NONDIABETIC WOMEN SO DIABETES CARE LA English DT Article ID HIGH-CARBOHYDRATE; ENERGY-INTAKE; MELLITUS; FAT; QUESTIONNAIRE; INDIVIDUALS; NIDDM; MEN AB OBJECTIVE - To assess the dietary habits of diabetic women. RESEARCH DESIGN AND METHODS - Participants in the Nurses Health Study, a cohort of 121,700 registered female nurses, were followed since 1976. We compared the usual dietary intakes of women who had been diagnosed with diabetes mellitus by 1980 and age-matched nondiabetic control women, diets of these women were assessed in 1980 and 1984 by a semiquantitative food frequency questionnaire. The study examined 162 IDDM women and 738 NIDDM women. Similar comparisons were made for 429 women who developed NIDDM between 1980 and 1984. RESULTS - Although differences were small, women with IDDM in 1984 and women with NIDDM in 1980 and 1984 consumed less energy from carbohydrates, especially from sucrose, and more energy from protein and fat than did control women. Similar results were also found in 1984 for the 429 women who developed NIDDM between 1980 and 1984. In 1980, energy from nonsucrose carbohydrate was slightly higher in both IDDM and NIDDM women than in the control women. However, in 1984, using a dietary questionnaire designed to assess more complete dietary intake, less consistent results were obtained. Diabetic women tended to avoid desserts and sweets, sugar-containing beverages, and alcoholic beverages but consumed more meat and meat products. Intakes of foods high in complex carbohydrates (e.g., bread, rice, pasta, and potatoes) were similar between diabetic and control women. CONCLUSIONS - The results suggest that these diabetic women did not consume the high-carbohydrate, low-fat diets that the American Diabetes Association has been recommending over the past decade. C1 HARVARD UNIV,SCH MED,CHANNING LAB,DEPT MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. RP SHIMAKAWA, T (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPL,FED BLDG,ROOM 2C03,7550 WISCONSIN AVE,BETHESDA,MD 20892, USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA-40356]; NIDDK NIH HHS [DK-36798] NR 27 TC 27 Z9 28 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 1993 VL 16 IS 10 BP 1356 EP 1362 DI 10.2337/diacare.16.10.1356 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LY180 UT WOS:A1993LY18000005 PM 8269793 ER PT J AU COONROD, BA ELLIS, D BECKER, DJ BUNKER, CH KELSEY, SF LLOYD, CE DRASH, AL KULLER, LH ORCHARD, TJ AF COONROD, BA ELLIS, D BECKER, DJ BUNKER, CH KELSEY, SF LLOYD, CE DRASH, AL KULLER, LH ORCHARD, TJ TI PREDICTORS OF MICROALBUMINURIA IN INDIVIDUALS WITH IDDM SO DIABETES CARE LA English DT Article ID DEPENDENT DIABETES-MELLITUS; URINARY ALBUMIN EXCRETION; SODIUM-LITHIUM COUNTERTRANSPORT; ESSENTIAL-HYPERTENSION; BLOOD-PRESSURE; PITTSBURGH EPIDEMIOLOGY; NATURAL-HISTORY; FAMILY HISTORY; RENAL-DISEASE; NEPHROPATHY AB OBJECTIVE- To examine the relationships between microalbuminuria and the development of overt diabetic nephrology, elevated blood pressure, and a more atherogenic lipid profile; and to identify risk factors for the development of microalbuminuria in individuals with IDDM. Microalbuminuria has been associated with the subsequent development of overt diabetic nephropathy in individuals with IDDM. it is associated with elevated blood pressure and a more atherogenic lipid profile, but the temporal relationship between the development of microalbuminuria and the changes in these factors is unclear. RESEARCH DESIGN AND METHODS - Baseline characteristics were examined in 256 individuals with IDDM who had normal albumin excretion (urinary AER less-than-or-equal-to 20 mug/min in greater-than-or-equal-to 2 timed urine collections) and were re-examined 2 yr later. RESULTS- At follow-up, 24 had developed microalbuminuria (AER 20-200 mug/min in greater-than-or-equal-to 2 timed urine collections) and 1 had developed overt nephropathy (AER > 2 00 mug/min). Overall, the significant independent predictors of microalbuminuria were HbA1 (P < 0.001), low-density lipoprotein (P < 0.01), duration of IDDM (P < 0.05), and systolic blood pressure (P = 0.05). Sex-specific analyses showed HbA1, age, and baseline AER were particularly important for men; whereas, for women, the main predictors were duration of IDDM and triglycerides. Duration-specific analyses showed that HbA, was an important predictor both for individuals with < and > 20-yr duration. Low-density lipoprotein cholesterol was more important for subjects with shorter durations; whereas triglycerides were important for those with longer durations. CONCLUSIONS- These results suggest that glycemic control, age or duration of IDDM, disturbed lipids, and possibly elevated blood pressure all may contribute to the development of microalbuminuria; and, further, that the adverse cardiovascular risk profile seen in individuals with overt nephropathy may begin to develop even before the detection of microalbuminuria. C1 CHILDRENS HOSP,DIABET RES CTR,RANGOS RES CTR,5TH FLOOR,3460 5TH AVE,PITTSBURGH,PA 15213. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT EPIDEMIOL,PITTSBURGH,PA 15260. CHILDRENS HOSP,DIV NEPHROL & PEDIAT ENDOCRINOL,PITTSBURGH,PA 15213. CHILDRENS HOSP,DIV METAB,PITTSBURGH,PA 15213. CHILDRENS HOSP,DIV DIABET MELLITUS,PITTSBURGH,PA 15213. NIDDKD,BETHESDA,MD. OI orchard, trevor/0000-0001-9552-3215 FU NIDDK NIH HHS [DK-34-818] NR 46 TC 150 Z9 156 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 1993 VL 16 IS 10 BP 1376 EP 1383 DI 10.2337/diacare.16.10.1376 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LY180 UT WOS:A1993LY18000008 PM 8269796 ER PT J AU NELSON, RG PETTITT, DJ BAIRD, HR CHARLES, MA LIU, QZ BENNETT, PH KNOWLER, WC AF NELSON, RG PETTITT, DJ BAIRD, HR CHARLES, MA LIU, QZ BENNETT, PH KNOWLER, WC TI PREDIABETIC BLOOD-PRESSURE PREDICTS URINARY ALBUMIN EXCRETION AFTER THE ONSET OF TYPE-2 (NON-INSULIN-DEPENDENT) DIABETES-MELLITUS IN PIMA-INDIANS SO DIABETOLOGIA LA English DT Article DE ALBUMINURIA; RISK FACTORS; BLOOD PRESSURE; TYPE-2 (NON-INSULIN-DEPENDENT) DIABETES-MELLITUS; PIMA INDIANS ID SODIUM-LITHIUM COUNTERTRANSPORT; RENAL-DISEASE; NEPHROPATHY; PROTEINURIA; MICROALBUMINURIA; SAMPLES; HYPERTENSION; PROGRESSION; PREVALENCE; ROCHESTER AB Blood pressure was measured in 490 non-proteinuric Pima Indians from the Gila River Indian Community in Arizona at least 1 year before the diagnosis of Type 2 (non-insulin-dependent) diabetes mellitus. Urine albumin concentration was measured in the same subjects 0-24 years (mean 5 years) after diabetes was diagnosed. Prevalence rates of abnormal albumin excretion (albumin-to-creatinine ratio greater-than-or-equal-to 100 mg/g) after the onset of Type 2 diabetes were 9 %, 16 %, and 23 %, respectively, for the lowest to highest tertiles of pre-diabetic mean blood pressure. When controlled for age, sex, duration of diabetes and pre-diabetic 2-h post-load plasma glucose concentration, higher pre-diabetic mean blood pressure predicted abnormal urinary excretion of albumin after the onset of diabetes. This finding suggests that the higher blood pressure seen in diabetic nephropathy is not entirely a result of the renal disease, but may precede and contribute to it. C1 NIDDKD, PHOENIX EPIDEMIOL & CLIN RES BRANCH, DIABET & ARTHRITIS EPIDEMIOL SECT, PHOENIX, AZ USA. RP NELSON, RG (reprint author), CLEVELAND CLIN FDN, DEPT BIOSTAT & EPIDEMIOL, 1616 E INDIAN SCH RD, PHOENIX, AZ 85016 USA. RI Nelson, Robert/B-1470-2012 FU NIDDK NIH HHS [N01-DK-6-2285] NR 33 TC 90 Z9 91 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD OCT PY 1993 VL 36 IS 10 BP 998 EP 1001 DI 10.1007/BF02374490 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LZ223 UT WOS:A1993LZ22300025 PM 8243885 ER PT J AU NELSON, RG KNOWLER, WC MCCANCE, DR SIEVERS, ML PETTITT, DJ CHARLES, MA HANSON, RL LIU, QZ BENNETT, PH AF NELSON, RG KNOWLER, WC MCCANCE, DR SIEVERS, ML PETTITT, DJ CHARLES, MA HANSON, RL LIU, QZ BENNETT, PH TI DETERMINANTS OF END-STAGE RENAL-DISEASE IN PIMA-INDIANS WITH TYPE-2 (NON-INSULIN-DEPENDENT) DIABETES-MELLITUS AND PROTEINURIA SO DIABETOLOGIA LA English DT Article DE DIABETIC NEPHROPATHY; PROTEINURIA; END-STAGE RENAL DISEASE; TYPE-2 (NON-INSULIN-DEPENDENT) DIABETES-MELLITUS; BLOOD PRESSURE; PIMA INDIANS ID CORONARY HEART-DISEASE; FOLLOW-UP; URINE SAMPLES; RISK-FACTORS; NEPHROPATHY; MORTALITY; RETINOPATHY; POPULATION; PREVALENCE; NIDDM AB To identify factors related to the development of end-stage renal disease after the onset of proteinuria, its incidence was determined in 364 Pima Indians aged 35 years or older with Type 2 (non-insulin-dependent) diabetes mellitus and proteinuria (protein-to-creatinine ratio greater-than-or-equal-to 0.5 g/g). Of these 364 subjects, 95 (36 men, 59 women) developed end-stage renal disease. The cumulative incidence was 40% 10 years after and 61 % 15 years after the onset of proteinuria. The incidence of end-stage renal disease was significantly related to the duration of diabetes, the duration of proteinuria, higher 2-h plasma glucose concentration, type of diabetes treatment, and the presence of retinopathy at the time of recognition of the proteinuria, but not to age, sex, or blood pressure. Duration of proteinuria influenced the risk of end-stage renal disease, contingent, however, upon the duration of diabetes at the onset of proteinuria. The higher cumulative incidence of end-stage renal disease 15 years after the onset of proteinuria in Pima Indians (61 %) than in Caucasians from Rochester, Minnesota (17 %) may be attributable, in part, to the younger age of onset of Type 2 diabetes in Pima Indians than in Caucasians, to ethnic differences in susceptibility to renal disease, or to lower death rates among the Pima Indians from competing causes of death, such as coronary heart disease. C1 NIDDKD, PHOENIX EPIDEMIOL & CLIN RES BRANCH, DIABET & ARTHRITIS EPIDEMIOL SECT, PHOENIX, AZ USA. RP NELSON, RG (reprint author), CLEVELAND CLIN FDN, DEPT BIOSTAT & EPIDEMIOL, 1616 E INDIAN SCH RD, SUITE 125, PHOENIX, AZ 85016 USA. RI Nelson, Robert/B-1470-2012; Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU NIDDK NIH HHS [N01-DK-6-2285, N01-DK-7-2292] NR 64 TC 51 Z9 51 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD OCT PY 1993 VL 36 IS 10 BP 1087 EP 1093 DI 10.1007/BF02374503 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LZ223 UT WOS:A1993LZ22300038 PM 8243859 ER PT J AU SIZEMORE, N KASTURI, L GORODESKI, G ECKERT, RL JETTEN, AM RORKE, EA AF SIZEMORE, N KASTURI, L GORODESKI, G ECKERT, RL JETTEN, AM RORKE, EA TI RETINOID REGULATION OF HUMAN ECTOCERVICAL EPITHELIAL-CELL TRANSGLUTAMINASE ACTIVITY AND KERATIN GENE-EXPRESSION SO DIFFERENTIATION LA English DT Article ID HUMAN EPIDERMAL-CELLS; TERMINAL DIFFERENTIATION; VITAMIN-A; INTERMEDIATE FILAMENTS; ENVELOPE FORMATION; MOLECULAR-BIOLOGY; MESSENGER-RNA; ACID RECEPTOR; SEX STEROIDS; PROTEINS AB Cornified envelope formation, the level of transglutaminase activity and the pattern of cytokeratin gene expression are important biochemical markers of cervical epithelial cell differentiation in vivo. In the present study we examine the effects of retinoid treatment on transglutaminase (TG) activity and keratin gene expression in cultured human ectocervical epithelial cells (ECE cells). All-trans-retinoic acid (RA) and a synthetic retinoid, Ro 13-6298, suppress TG activity by 85-90% with half-maximal inhibition at 0.1 nM Ro 13-6298 or 1 nM RA. In contrast, the predominant circulating retinoid, retinol, does not inhibit TG activity. The level of type I transglutaminase protein, measured using a type I TG-specific antibody, decreases in parallel with the decrease in activity as does the level of the TG RNA transcript. Cytokeratin K16 decreases more than 20-fold while the level of K7, K8 and K19 increase 5 to 10-fold in the presence of 10 nM RA. Studies using cDNAs encoding K5, K13, K16 and K19 indicate that the RNA transcript levels change in parallel with the change in keratin protein production. Thus, all-trans-retinoic acid suppresses ectocervical epithelial cell differentiation in vitro, a result that suggests an in vivo role for retinoids in regulating cervical cell differentiation. C1 CASE WESTERN RESERVE UNIV,SCH MED,DEPT ENVIRONM HLTH SCI,2109 ADELBERT RD,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,SCH MED,DEPT REPROD BIOL,CLEVELAND,OH 44106. NIEHS,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC 27713. CASE WESTERN RESERVE UNIV,SCH MED,DEPT PHYSIOL & BIOPHYS,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,SCH MED,DEPT BIOCHEM,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,SCH MED,DEPT DERMATOL,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,SCH MED,DEPT REPROD BIOL,CLEVELAND,OH 44106. OI Jetten, Anton/0000-0003-0954-4445 FU NIAMS NIH HHS [AR39750]; NICHD NIH HHS [HD25135]; NIEHS NIH HHS [ES05227] NR 48 TC 24 Z9 25 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0301-4681 J9 DIFFERENTIATION JI Differentiation PD OCT PY 1993 VL 54 IS 3 BP 219 EP 225 DI 10.1111/j.1432-0436.1993.tb01603.x PG 7 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA MD908 UT WOS:A1993MD90800006 PM 7505756 ER PT J AU VINAYEK, R HAHNE, WF EULER, AR NORTON, JA JENSEN, RT AF VINAYEK, R HAHNE, WF EULER, AR NORTON, JA JENSEN, RT TI PARENTERAL CONTROL OF GASTRIC-ACID HYPERSECRETION IN PATIENTS WITH ZOLLINGER-ELLISON SYNDROME SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE GASTRINOMA; HISTAMINE-H(2)-RECEPTOR ANTAGONISTS; PEPTIC ULCER DISEASE ID PEPTIC-ULCER DISEASE; MALIGNANT GASTRINOMA; CIMETIDINE; MANAGEMENT; RANITIDINE; THERAPY; EXPERIENCE; OMEPRAZOLE; DIAGNOSIS; STATES AB Parenteral control of gastric acid hypersecretion in patients with Zollinger-Ellison syndrome is increasingly required; however, existing methods of determining the required dose are cumbersome and not applicable in all centers. A previous study suggested that the required parenteral dose of histamine H-2-receptor antagonists correlated with the previous oral dose. In the present study, in 31 patients with Zollinger-Ellison syndrome we evaluated the hypothesis that an effective parenteral histamine H-2-receptor antagonist dose could be predicted from the previous oral dose. Twenty-three patients were taking oral ranitidine (mean 1.3 g/day), six patients famotidine (152 mg/day), and two patients cimetidine (1.8 g/day). Each patient was treated with a continuous intravenous infusion of the equivalent dose of ranitidine (mean dose 1 mg/kg/hr with 35% requiring 0.5 mg/kg/hr, 49% 1 mg/kg/hr, 3% 1.5 mg/kg/hr, 10% 2 mg/kg/hr, and 3% 25 mg/kg/hr. This dose of ranitidine acutely controlled acid secretion (< 10 meq/hr) in all patients. To evaluate long-term efficacy and safety, 20 patients were maintained on this dose through the peri- and postoperative periods. Mean duration was 7.1 days with 25% treated 3-5 days, 40% 6-8 days, 30% 8-10 days, and 5% > 10 days. The predicted dose continued to control acid secretion in 95% of patients with one patient requiring one dose adjustment. No biochemical, clinical, or hematological toxicity was seen, although ranitidine was stopped in one patient because of skin rash. These results demonstrate that the parenteral dose of ranitidine required to control acid secretion in patients with Zollinger-Ellison syndrome can be predicted from the oral dose. This predicted dose will be acutely effective in all patients in reducing acid secretion to <10 meq/hr, the established level of control, will remain effective in 95% of patients for up to 11 days, and is safe. By utilizing the oral dose to predict the intravenous dose, repeated dose titrations will be avoided and thus this method should be generally useful in all settings. C1 NIDDKD,DIGEST DIS BRANCH,BLDG 10,ROOM 9C-103,BETHESDA,MD 20892. UNIV MARYLAND,DIV GASTROENTEROL,BALTIMORE,MD 21201. GLAXO INC,RES TRIANGLE PK,NC. NR 41 TC 7 Z9 7 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD OCT PY 1993 VL 38 IS 10 BP 1857 EP 1865 DI 10.1007/BF01296110 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA MB727 UT WOS:A1993MB72700014 PM 8104773 ER PT J AU DONOHUE, SJ ROSEBOOM, PH ILLNEROVA, H WELLER, JL KLEIN, DC AF DONOHUE, SJ ROSEBOOM, PH ILLNEROVA, H WELLER, JL KLEIN, DC TI HUMAN HYDROXYINDOLE-O-METHYLTRANSFERASE - PRESENCE OF LINE-1 FRAGMENT IN A CDNA CLONE AND PINEAL MESSENGER-RNA SO DNA AND CELL BIOLOGY LA English DT Article ID HUMAN TRANSPOSABLE ELEMENT; HUMAN CIRCADIAN-RHYTHMS; INFANT-DEATH-SYNDROME; MOLECULAR-CLONING; NUCLEOTIDE-SEQUENCE; PHOTOPERIODIC CONTROL; CEREBROSPINAL-FLUID; MELATONIN SECRETION; PLASMA MELATONIN; SYRIAN-HAMSTERS AB Hydroxyindole-0-methyltransferase (HIOMT) catalyzes the last step in the synthesis of the pineal hormone melatonin. In this study, an HIOMT clone was isolated from a human pineal cDNA library using synthetic oligonucleotide probes based on the bovine HIOMT sequence. The human sequence is unusual because it contains a 3' fragment (84 bp) of the LINE-1 sequence, a highly repetitive sequence in the human genome and the genome of some primates and rodents. Exclusive of this LINE-1 fragment, the human HIOMT clone is 75% and 63% homologous to bovine and avian HIOMT sequences, respectively. The deduced amino acid sequence of the human cDNA clone encodes a 41.6-kD protein. In addition, the sequence is 70% and 57% identical and 81% and 73% similar to bovine and avian HIOMT, respectively. In agreement with the results of earlier studies, it was found that vertebrate HIOMT amino acid sequences are not homologous to any other vertebrate proteins, including several methyltransferases. However, HIOMT exhibits homology with a plant 0-methyltransferase and an internal 120-amino-acid region is approximately 35% identical to a region of four bacterial 0-methyltransferases. The results of PCR and Southern blot analysis indicate that three species of HIOMT mRNA are typically present in the human pineal gland, only one of which contains the LINE-1 fragment. An antiserum was raised against a mixture of three synthetic peptides, corresponding to three regions of the deduced amino acid sequence of human HIOMT. This antiserum detected a single immunoreactive protein in Western blot analysis of human pineal glands. The size of the protein (approximately 42 kD) is identical to that predicted from the HIOMT clone, including the LINE-1 fragment. The human HIOMT sequence should be useful in further studies of this enzyme and will also be of special importance in evaluating the functional significance of the inclusion of a fragment of the LINE-1 in an mRNA. C1 NICHHD,DEV NEUROBIOL LAB,NEUROENDOCRINOL SECT,BLDG 99,ROOM 6A80,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,TOXICOL BRANCH,ROCKVILLE,MD 20892. INST PHYSIOL,PRAGUE,CZECHOSLOVAKIA. RI Illnerova, Helena/G-3898-2014 NR 63 TC 34 Z9 35 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD OCT PY 1993 VL 12 IS 8 BP 715 EP 727 DI 10.1089/dna.1993.12.715 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA ME736 UT WOS:A1993ME73600007 PM 8397829 ER PT J AU KAVSAN, VM KOVAL, AP GREBENJUK, VA CHAN, SJ STEINER, DF ROBERTS, CT LEROITH, D AF KAVSAN, VM KOVAL, AP GREBENJUK, VA CHAN, SJ STEINER, DF ROBERTS, CT LEROITH, D TI STRUCTURE OF THE CHUM SALMON INSULIN-LIKE GROWTH FACTOR-I GENE SO DNA AND CELL BIOLOGY LA English DT Article ID NUCLEOTIDE-SEQUENCE; MESSENGER-RNA; DNA FRAGMENTS; CDNAS; EXPRESSION; PROMOTER; CLONING; GELS AB insulin-like growth factor I (IGF-1) plays a major role in development and metabolism. Currently, the cDNA-derived primary structure of IGF-I is known for some mammals and for chicken, frog, and salmon. Additionally, the organization of the human, rat, and chicken IGF-I genes has been established. The investigation of IGF-I gene structure in fish would extend the evolutionary picture for this hormone and facilitate our understanding of the features of the IGF-I gene that are common to all vertebrate species. The cloned chum salmon IGF-I gene appears to be much more compact than the mammalian and avian genes, being less than 20 kb in length. As in other species, however, the mature IGF-I peptide appears to consist of 70 amino acids and is encoded by exons 2 and 3. Intriguingly, exon 1-encoded 5'-untranslated region sequences are highly conserved, while the coding sequences at the 3' end of the same exon are less conserved. The amino terminus of the signal peptide is four amino acids shorter than in the mammalian and avian peptides. The end of the B domain, the C, A, and D domains, and the first part of the E peptide are encoded by exon 3, but the exon 3-encoded E peptide sequence is 27 amino acids longer than in other species. These extra 27 amino acids, encoded by both coho and chum salmon cDNAs, may be deleted by alternative splicing, as suggested from the sequence of a coho salmon IGF-I cDNA. However, the substitution of AT for GT at the necessary splice donor site in the chum salmon IGF-I gene does not allow for the deletion of the sequence encoding these amino acids. The presence of additional chum salmon cDNAs that do not encode this 27-amino-acid sequence suggests the presence of a second chum salmon IGF-I gene with a functional splice junction at this location. Indeed, preliminary mapping data and partial sequencing suggests the existence of a second IGF-I gene in chum salmon. These observations show that the IGF-I genes in four classes of vertebrates have similar overall structures with regard to their common coding regions, but differ significantly in their 5' and 3' regions. C1 NIDDKD,DIABET BRANCH,BLDG 10,RM 85239,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. UKRAINIAN ACAD SCI,INST MOLEC BIOL & GENET,DEPT BIOSYNTH NUCLEIC ACIDS,KIEV 252627,UKRAINE. UNIV CHICAGO,DEPT BIOCHEM & MOLEC BIOL,CHICAGO,IL 60637. UNIV CHICAGO,HOWARD HUGHES MED INST,CHICAGO,IL 60637. OI Roberts, Charles/0000-0003-1756-5772 NR 28 TC 34 Z9 37 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD OCT PY 1993 VL 12 IS 8 BP 729 EP 737 DI 10.1089/dna.1993.12.729 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA ME736 UT WOS:A1993ME73600008 PM 8397830 ER PT J AU LEHN, DA BUSTIN, M AF LEHN, DA BUSTIN, M TI EVOLUTIONARILY CONSERVED MOTIFS AND PROTEIN-BINDING ELEMENTS IN THE 5' REGION OF THE CHROMOSOMAL PROTEIN HMG-14 GENE SO DNA AND CELL BIOLOGY LA English DT Article ID HUMAN CDNA SEQUENCE; SINGLE COPY GENE; MULTIGENE FAMILY; FUNCTIONAL GENE; CELL-CYCLE; DIFFERENTIATION; IDENTIFICATION; TRANSCRIPTION; LOCALIZATION; FEATURES AB Although the structure of several genes coding for chromosomal proteins HMG-14 and HMG-17 has been determined, the mechanisms regulating the expression of these genes has not yet been examined. Toward this goal, we have cloned and sequenced a fragment containing the first three exons and 956 bp upstream from the start of translation of the functional mouse HMG-14 gene. Comparison of this sequence to the known sequence of the human HMG-14 gene revealed the presence of five distinct blocks of high sequence identity flanking the start of transcription and the CAAT box. DNase I and mobility-shift analysis identified a DNA region, downstream from the start of transcription, which may be important for the formation of a stable protein-DNA complex. Affinity chromatography on columns containing oligonucleotides corresponding to this sequence indicates that this region is a protein binding site. C1 NCI,MOLEC CARCINOGENESIS LAB,PROT SECT,BLDG 37,RM 3D12,BETHESDA,MD 20892. RI Bustin, Michael/G-6155-2015 NR 34 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD OCT PY 1993 VL 12 IS 8 BP 753 EP 761 DI 10.1089/dna.1993.12.753 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA ME736 UT WOS:A1993ME73600010 PM 8397832 ER PT J AU NIKODIJEVIC, O JACOBSON, KA DALY, JW AF NIKODIJEVIC, O JACOBSON, KA DALY, JW TI EFFECTS OF COMBINATIONS OF METHYLXANTHINES AND ADENOSINE-ANALOGS ON LOCOMOTOR-ACTIVITY IN CONTROL AND CHRONIC CAFFEINE-TREATED MICE SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE ADENOSINE RECEPTORS; CAFFEINE; ADENOSINE ANALOGS; BEHAVIOR; LOCOMOTOR ACTIVITY ID PHOSPHODIESTERASE INHIBITORS; RECEPTORS; ANTAGONISTS; THEOPHYLLINE; TOLERANCE; AFFINITY; BINDING; SYSTEM AB Chronic caffeine ingestion (CCl) by male NIH Swiss strain mice results in a prolonged reduction in locomotor activity and alterations in response to caffeine, other xanthines, and adenosine analogs. Caffeine, the A1 selective 8-cyclopentyltheophylline (CPT), and the A2-selective 3,7-dimethyl-1-propargylxanthine (DMPX) remain stimulatory and the bell-shaped locomotor dose-response curves are left-shifted after CCI. The depressant effects of methylxanthines that are potent phosphodiesterase inhibitors remain after CCI. After CCI, mice became more sensitive to depressant effects of A1, mixed A1/A2, and A2 agonists. In the presence of caffeine the A1-selective agonist N6-cyclohexyladenosine (CHA), the mixed A1/A2 agonist 5'-N-ethylcarboxamidoadenosine and the A2-selective agonist 2-[(2-aminoethylamino)-carbonylethylphenylethylamino]-5'-N-ethylcarboxamidoadenosine (APEC) all have dose-response curves, appearing to consist of initial depressant effects, then stimulatory effects, and finally pronounced depressant effects. The phasic character is reduced or absent after CCI. Synergistic depressant effects of combinations of CHA and APEC also appear reduced after CCI. (C) 1993 Wiley-Liss, Inc.* C1 NIDDKD,BIOORGAN CHEM LAB,BLDG 8,ROOM 1A-17,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 25 TC 13 Z9 13 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD OCT PY 1993 VL 30 IS 2 BP 104 EP 110 DI 10.1002/ddr.430300209 PG 7 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MG333 UT WOS:A1993MG33300007 ER PT J AU MAHER, JE GOLDENBERG, RL TAMURA, T CLIVER, SP HOFFMAN, HJ DAVIS, RO BOOTS, L AF MAHER, JE GOLDENBERG, RL TAMURA, T CLIVER, SP HOFFMAN, HJ DAVIS, RO BOOTS, L TI ALBUMIN LEVELS IN PREGNANCY - A HYPOTHESIS - DECREASED LEVELS OF ALBUMIN ARE RELATED TO INCREASED LEVELS OF ALPHA-FETOPROTEIN SO EARLY HUMAN DEVELOPMENT LA English DT Article DE ALBUMIN; ALPHA-FETOPROTEIN; PREGNANCY ID HEPATOMA-CELL LINE; MATERNAL SERUM; EXPRESSION; AFP AB Serum albumin levels decrease during pregnancy while the concentration of most other maternal serum proteins of hepatic origin remain stable or increase. In a study of 289 women, most maternal characteristics such as race, age, smoking, a history of previous low birthweight, infant sex and gestational age at delivery were not related to maternal serum albumin levels at 18 or 30 weeks' gestational age. The degree of maternal obesity significantly correlated with the concentration of albumin. There was a significant negative correlation in individual women between maternal serum levels of albumin and alpha-fetoprotein, with high levels of maternal serum alpha-fetoprotein predicting lower levels of albumin. We hypothesize that there may be a negative feedback effect of alpha-fetoprotein of fetal origin on the maternal production of albumin during pregnancy. C1 UNIV ALABAMA,DEPT NUTR SCI,PERINATAL EPIDEMIOL UNIT,BIRMINGHAM,AL 35233. NICHHD,PREVENT RES PROGRAM,BETHESDA,MD 20892. RP MAHER, JE (reprint author), UNIV ALABAMA,DEPT OBSTET & GYNECOL,BIRMINGHAM,AL 35233, USA. FU NICHD NIH HHS [N01-HD-4-2811] NR 23 TC 13 Z9 13 U1 2 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-3782 J9 EARLY HUM DEV JI Early Hum. Dev. PD OCT PY 1993 VL 34 IS 3 BP 209 EP 215 DI 10.1016/0378-3782(93)90178-W PG 7 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA ME098 UT WOS:A1993ME09800004 PM 7507040 ER PT J AU FUHR, P HALLETT, M AF FUHR, P HALLETT, M TI RECIPROCAL INHIBITION OF THE H-REFLEX IN THE FOREARM - METHODOLOGICAL ASPECTS SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE RECIPROCAL INHIBITION; H-REFLEX; DYSTONIA ID I FIBER PROJECTIONS; HUMAN UPPER LIMB; MUSCLE AFFERENTS; FACILITATION; TRANSMISSION; STIMULATION; RESPONSES; PATHWAYS; PATTERN; NERVES AB Reciprocal inhibition of the H-reflex in the wrist flexors elicited by stimulation of the radial nerve provides insight into the pathophysiology of different kinds of dystonia and may become a diagnostic tool for some movement disorders. Some of the results have been conflicting, however, owing presumably to differences in the technique. The present study in normal subjects shows that the amount of inhibition increases with decreasing amplitude of the unconditioned H-reflex and with increasing intensity of the radial nerve stimulus. Duration of the stimulus is important: stimuli of short duration are ineffective, and stimuli of long duration produce inconsistent inhibition. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BETHESDA,MD 20892. NR 29 TC 16 Z9 17 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0013-4694 J9 ELECTROEN CLIN NEURO JI Electroencephalogr. Clin. Neurophysiol. PD OCT PY 1993 VL 89 IS 5 BP 319 EP 327 DI 10.1016/0168-5597(93)90071-V PG 9 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA MF160 UT WOS:A1993MF16000004 PM 7691571 ER PT J AU NILSSON, J PANIZZA, M HALLETT, M AF NILSSON, J PANIZZA, M HALLETT, M TI PRINCIPLES OF DIGITAL SAMPLING OF A PHYSIOLOGICAL SIGNAL SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE EMG; NERVE CONDUCTION VELOCITY; EEG AND EVOKED POTENTIALS; FREQUENCY RANGES; FILTERS; SAMPLING FREQUENCY; NYQUIST THEOREM; FOURIER TRANSFORM ID EVOKED-POTENTIALS; SPECTRUM AB The practice of clinical neurophysiology requires fast, reliable and accurate assessment of a variety of biologic signals. Appropriate filters and rates of analog-to-digital sampling must be used to avoid distorting the signal. Using principles of sampling theory and examples, we describe the frequency content of signals encountered in clinical neurophysiology laboratories, offer guidelines for band-limiting frequencies, and give rules for determining minimal sampling frequencies. Errors introduced by undersampling (aliasing) are illustrated. When sophisticated computational techniques, such as discrete Fourier transform, are used to reconstruct the original wave form, a sampling frequency just above the double of the highest frequency content of the signal is adequate. Sampling neurophysiologic wave forms for direct display, however, requires a sampling frequency at least 4 times as high as that of the upper frequency filter. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BETHESDA,MD 20892. FDN CLIN LAVORO,CLIN NEUROPHYSIOL LAB,CASTEL GOFFREDO,ITALY. NR 16 TC 20 Z9 21 U1 2 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0013-4694 J9 ELECTROEN CLIN NEURO JI Electroencephalogr. Clin. Neurophysiol. PD OCT PY 1993 VL 89 IS 5 BP 349 EP 358 DI 10.1016/0168-5597(93)90075-Z PG 10 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA MF160 UT WOS:A1993MF16000008 PM 7691575 ER PT J AU ROTH, BJ BALISH, M GORBACH, A SATO, S AF ROTH, BJ BALISH, M GORBACH, A SATO, S TI HOW WELL DOES A 3-SPHERE MODEL PREDICT POSITIONS OF DIPOLES IN A REALISTICALLY SHAPED HEAD SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE EEG; DIPOLE; LOCALIZATION; REALISTICALLY SHAPED HEAD MODEL; 3-SPHERE MODEL ID EEG; MEGS AB The electrical potential produced by a dipole in the temporal or frontal lobe was calculated for a realistically shaped scalp, skull, and brain. This potential distribution was then used with a 3-sphere model to predict the position, orientation, and strength of the dipole source. The original and predicted dipole positions differed by an average of 1.97 cm, with a difference of more than 4 cm in some cases. Control calculations demonstrated that this difference was not caused by numerical artifacts in the computation, but instead was due to a true difference between the 3-sphere and realistically shaped head models. C1 GEORGETOWN UNIV HOSP,DEPT NEUROL,WASHINGTON,DC 20007. NINCDS,EPILEPSY RES BRANCH,CLIN NEUROPHYSIOL UNIT,BETHESDA,MD 20892. RP ROTH, BJ (reprint author), NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 13,ROOM 3W13,BETHESDA,MD 20892, USA. RI Roth, Bradley/A-4920-2008 NR 19 TC 108 Z9 108 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0013-4694 J9 ELECTROEN CLIN NEURO JI Electroencephalogr. Clin. Neurophysiol. PD OCT PY 1993 VL 87 IS 4 BP 175 EP 184 DI 10.1016/0013-4694(93)90017-P PG 10 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA MG586 UT WOS:A1993MG58600002 PM 7691548 ER PT J AU WHEELER, D CHRAMBACH, A AF WHEELER, D CHRAMBACH, A TI THE FRACTIONAL VOLUME AVAILABLE TO PROLATE SPHEROIDS IN A NETWORK OF RANDOMLY ORIENTED FIBERS OBTAINED BY COMPUTER MODELING - CORRELATION WITH THE OGSTON EQUATION SO ELECTROPHORESIS LA English DT Article AB Computer modeling was used to measure the fractional volumes available to prolate spheroid objects in a random, inert network of fibers. The data fit the Ogston equation exactly when the object was a sphere (axial ratio = 1). When the axial ratio was increased from 1 to 9, the Ogston equation was still obeyed if the fiber concentration is multiplied by a factor, A, which increases linearly in proportion to the axial ratio. The factor A allows one to adjust the retardation coefficient derived from gel electrophoresis, K(R), for spherical objects to that of prolate spheroids with axial ratios from 1 to 9. Potentially, the same adjustment of K(R) is possible for objects of other shapes. RP WHEELER, D (reprint author), NICHHD,BLDG 10,RM 6C-101,BETHESDA,MD 20892, USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD OCT PY 1993 VL 14 IS 10 BP 993 EP 996 DI 10.1002/elps.11501401158 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA MJ117 UT WOS:A1993MJ11700006 PM 8125067 ER PT J AU FAZIOLI, F MINICHIELLO, L MATOSKA, V CASTAGNINO, P MIKI, T WONG, WT DIFIORE, PP AF FAZIOLI, F MINICHIELLO, L MATOSKA, V CASTAGNINO, P MIKI, T WONG, WT DIFIORE, PP TI EPS8, A SUBSTRATE FOR THE EPIDERMAL GROWTH-FACTOR RECEPTOR KINASE, ENHANCES EGF-DEPENDENT MITOGENIC SIGNALS SO EMBO JOURNAL LA English DT Article DE EGFR; SIGNAL TRANSDUCTION; SUBSTRATES; TYROSINE KINASES ID PHOSPHOLIPASE-C-GAMMA; PDGF BETA-RECEPTOR; PHOSPHOTYROSINE-CONTAINING PROTEINS; GTPASE-ACTIVATING PROTEIN; TYROSINE KINASES; MONOCLONAL-ANTIBODIES; TRANSFORMING PROTEIN; CDNA CLONING; SH2 DOMAINS; PHOSPHORYLATION AB A method which allows direct cloning of intracellular substrates for receptor tyrosine kinases (RTKs) was developed. By applying this technique to the study of the epidermal growth factor receptor (EGFR) signaling pathway, we have isolated a cDNA, designated eps8, which predicts a approximately 92 kDa protein containing an SH3 domain. Eps8 also contains a putative nuclear targeting sequence. Antibodies specific to the eps8 gene product recognize a protein of M(r) 97 kDa and a minor 68 kDa component, which are closely related, as demonstrated by V8 proteolytic mapping. The product of the eps8 gene is tyrosine-phosphorylated in vivo following EGF stimulation of intact cells and associates with the EGFR, despite the lack of a functional SH2 domain. Several other RTKs are also able to phosphorylate p97esp8. Thus, the eps8 gene product represents a novel substrate for RTKs. Adoptive expression of the eps8 cDNA in fibroblastic or hematopoietic target cells expressing the EGFR resulted in increased mitogenic response to EGF, implicating the eps8 gene product in the control of mitogenic signals. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RI Di Fiore, Pier Paolo/K-2130-2012 OI Di Fiore, Pier Paolo/0000-0002-2252-0950 NR 67 TC 144 Z9 153 U1 1 U2 6 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 PY 1993 VL 12 IS 10 BP 3799 EP 3808 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LY497 UT WOS:A1993LY49700011 PM 8404850 ER PT J AU CRIPPA, MP TRIESCHMANN, L ALFONSO, PJ WOLFFE, AP BUSTIN, M AF CRIPPA, MP TRIESCHMANN, L ALFONSO, PJ WOLFFE, AP BUSTIN, M TI DEPOSITION OF CHROMOSOMAL PROTEIN HMG-17 DURING REPLICATION AFFECTS THE NUCLEOSOMAL LADDER AND TRANSCRIPTIONAL POTENTIAL OF NASCENT CHROMATIN SO EMBO JOURNAL LA English DT Article DE ACTIVE CHROMATIN; CHROMATIN ASSEMBLY; CHROMOSOMAL PROTEINS; TRANSCRIPTION; XENOPUS ID MOBILITY GROUP PROTEINS; XENOPUS-LAEVIS OOCYTES; DNA-SEQUENCES; 5S-RNA GENE; INVITRO; INVOLVEMENT; HISTONES; COMPLEX; CORE; IMMUNOFRACTIONATION AB A cell-free system from Xenopus eggs was used to study the role of chromosomal protein HMG-17 in the generation of the chromatin structure of transcriptionally active genes. Addition of HMG-17 protein to the extracts, which do not contain structural homologs of the HMG-14/-17 protein family, indicates the protein is incorporated into the nascent template during replication, prior to completion of chromatin assembly. The protein binds to and stabilizes the structure of the nucleosomal core thereby improving the apparent periodicity of the nucleosomal spacing of nascent chromatin. Assembly of HMG-17 into the nascent chromatin structure significantly increased the transcription potential of the 5S RNA gene and satellite I chromatin. Kinetic studies indicate that the increase in transcriptional potential is observed only when HMG-17 is incorporated into nucleosomes during chromatin assembly. C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. RI crippa, massimo/J-6514-2016; Bustin, Michael/G-6155-2015 OI crippa, massimo/0000-0003-3214-9670; NR 61 TC 53 Z9 53 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 PY 1993 VL 12 IS 10 BP 3855 EP 3864 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LY497 UT WOS:A1993LY49700017 PM 8404854 ER PT J AU FRANZOSO, G BOURS, V AZARENKO, V PARK, S TOMITAYAMAGUCHI, M KANNO, T BROWN, K SIEBENLIST, U AF FRANZOSO, G BOURS, V AZARENKO, V PARK, S TOMITAYAMAGUCHI, M KANNO, T BROWN, K SIEBENLIST, U TI THE ONCOPROTEIN BCL-3 CAN FACILITATE NF-THETA-B-MEDIATED TRANSACTIVATION BY REMOVING INHIBITING P50 HOMODIMERS FROM SELECT THETA-B SITES SO EMBO JOURNAL LA English DT Article DE BCL-3; NF-THETA-B; ONCOPROTEIN; P50 HOMODIMERS; TRANSACTIVATION ID I-KAPPA-B; DNA-BINDING SUBUNIT; CANDIDATE PROTOONCOGENE BCL-3; TRANSCRIPTION FACTOR; PROTO-ONCOGENE; P65 SUBUNIT; V-REL; C-REL; RETICULOENDOTHELIOSIS VIRUS; CYTOPLASMIC RETENTION AB Previously we have proposed a role for Bcl-3 in facilitating transactivation through kappaB sites by counteracting the inhibitory effects of bound, non-transactivating homodimers of the p50 subunit of NF-kappaB. Such homodimers are abundant for example in nuclei of unstimulated primary T cells. Here we extend the model and provide new evidence which fulfills a number of predictions. (i) Bcl-3 preferentially targets p50 homodimers over NF-kappaB heterodimers since the homodimers are completely dissociated from kappaB sites at concentrations of Bcl-3 which do not affect NF-kappaB. (ii) Select kappaB sites associate very strongly and stably with p50 homodimers, completely preventing binding by NF-kappaB. Such kappaB sites are likely candidates for regulation by p50 homodimers and Bcl-3. (iii) Bcl-3 and p50 can be co-localized in the nucleus, a requirement for active removal of homodimers from their binding sites in vivo. (iv) The ankyrin repeat domain of Bcl-3 is sufficient for the reversal of p50 homodimer-mediated inhibition, correlating with the ability of this domain alone to inhibit p50 binding to kappaB sites in vitro. Our data support the model that induction of nuclear Bcl-3 may be required during cellular stimulation to actively remove stably bound p50 homodimers from certain kappaB sites in order to allow transactivating NF-kappaB complexes to engage. This exact mechanism is demonstrated with in vitro experiments. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. SERV MICROBIOL,COMPLESSO CONVENZ UNIV ULSS21,I-35100 PADUA,ITALY. NR 60 TC 127 Z9 128 U1 1 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD OCT PY 1993 VL 12 IS 10 BP 3893 EP 3901 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LY497 UT WOS:A1993LY49700020 PM 8404857 ER PT J AU PUTNEY, JW BIRD, GS AF PUTNEY, JW BIRD, GS TI THE INOSITOL PHOSPHATE-CALCIUM SIGNALING SYSTEM IN NONEXCITABLE CELLS SO ENDOCRINE REVIEWS LA English DT Review ID PAROTID ACINAR-CELLS; INTRACELLULAR CA2+ STORES; PROTEIN-KINASE-C; SMOOTH-MUSCLE CELLS; CYTOPLASMIC FREE CALCIUM; CYTOSOLIC FREE CALCIUM; SEA-URCHIN EGGS; 1,4,5-TRISPHOSPHATE-MEDIATED CA-2+ RELEASE; TRISPHOSPHATE-SENSITIVE STORES; ATPASE INHIBITOR THAPSIGARGIN RP PUTNEY, JW (reprint author), NIEHS,CELLULAR & MOLEC PHARMACOL LAB,CALCIUM REGULAT SECT,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 268 TC 501 Z9 504 U1 2 U2 9 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD OCT PY 1993 VL 14 IS 5 BP 610 EP 631 DI 10.1210/er.14.5.610 PG 22 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ME241 UT WOS:A1993ME24100006 PM 8262009 ER PT J AU SZKUDLINSKI, MW THOTAKURA, NR BUCCI, I JOSHI, LR TSAI, A EASTPALMER, J SHILOACH, J WEINTRAUB, BD AF SZKUDLINSKI, MW THOTAKURA, NR BUCCI, I JOSHI, LR TSAI, A EASTPALMER, J SHILOACH, J WEINTRAUB, BD TI PURIFICATION AND CHARACTERIZATION OF RECOMBINANT HUMAN THYROTROPIN (TSH) ISOFORMS PRODUCED BY CHINESE-HAMSTER OVARY CELLS - THE ROLE OF SIALYLATION AND SULFATION IN TSH BIOACTIVITY SO ENDOCRINOLOGY LA English DT Article ID THYROID-STIMULATING HORMONE; ASPARAGINE-LINKED OLIGOSACCHARIDES; PITUITARY GLYCOPROTEIN HORMONES; METABOLIC-CLEARANCE; ENZYMATIC DEGLYCOSYLATION; ALPHA-SUBUNIT; RAT FSH; GLYCOSYLATION; BIOSYNTHESIS; SECRETION AB The biological significance of glycosylation variants of pituitary glycoprotein hormones remains controversial because of the indirect methods usually employed to determine carbohydrate composition or structure as well as the use of unreliable biological/immunological ratio to determine bioactivity. We have previously characterized recombinant human TSH (rhTSH) secreted by Chinese hamster ovary cells attached to microcarrier beads in a large scale bioreactor after stable transfection of hCGalpha and hTSHbeta minigenes. In the present study rhTSH has been used as a model to determine structure-function relationships of different isoforms of glycoprotein hormones. We have now produced greater than 200 mg rhTSH using a hollow fiber bioreactor. The highly purified rhTSH produced in the hollow fiber bioreactor (rhTSH-N) as well as rhTSH commercially produced in a large scale bioreactor (rhTSH-G) were quantitated by immunoassays, receptor binding assay, and amino acid analysis and further characterized by a variety of physico-biochemical methods, including chromatofocusing and carbohydrate analysis. rhTSH-G, rhTSH-N, as well as pituitary human TSH (phTSH) have been separated by chromatofocusing on a Mono P column into several isoforms with different pI values. Compositional analysis of the fractions showed higher sialic acid content in the more acidic rhTSH-G fractions. phTSH acidic isoforms showed higher total sulfate and sialic acid contents than the more basic fractions. The bioactivities of various TSH isoforms based on rigorous quantitation of mass by amino acid analysis determined in three different FRTL-5 cell bioassays showed that the more basic and less sialylated fractions of rhTSH-G were more active than the more acidic fractions. In contrast to the in vitro data, highly sialylated and acidic rhTSH-G isoforms showed longer plasma half-lives and higher in vivo bioactivity than the basic forms. These results indicate that secreted rhTSH, similar to intrapituitary phTSH, exists as a mixture of charge isoforms that are related at least in part to the degree of sialylation. The degree of sialylation, highly dependent on the bioreactor production conditions, appears to be the major factor affecting the charge heterogeneity, MCR, and bioactivity of rhTSH. C1 NIDDK, CELLULAR & DEV BIOL LAB, MOLEC & CELLULAR ENDOCRINOL BRANCH,BLDG 10, ROOM 8014, BETHESDA, MD 20892 USA. NIDDK, CELLULAR & DEV BIOL LAB, BIOTECHNOL UNIT, BETHESDA, MD 20892 USA. NR 47 TC 114 Z9 115 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1993 VL 133 IS 4 BP 1490 EP 1503 DI 10.1210/en.133.4.1490 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MA411 UT WOS:A1993MA41100002 PM 8404588 ER PT J AU MAJANE, EA ZHU, JM AARNISALO, AA PANULA, P YANG, HYT AF MAJANE, EA ZHU, JM AARNISALO, AA PANULA, P YANG, HYT TI ORIGIN OF NEUROHYPOPHYSEAL NEUROPEPTIDE-FF (FLFQPQRF-NH2) SO ENDOCRINOLOGY LA English DT Article ID MORPHINE-MODULATING PEPTIDES; MAMMALIAN FMRF-NH2-LIKE PEPTIDE; STRESS-INDUCED ANALGESIA; CENTRAL-NERVOUS-SYSTEM; RAT SPINAL-CORD; FMRFAMIDE PHE-MET-ARG-PHE-NH2; BRATTLEBORO RAT; BRAIN; VASOPRESSIN; FLFQPQRFAMIDE AB Neuropeptide-FF (FLFQPQRF-NH2), originally isolated from bovine brain, is an FMRF-NH2-like peptide with morphine-modulating activity. Neuropeptide-FF (NPFF) is unevenly distributed in the central nervous system, with the highest concentrations in posterior pituitary and spinal cord. In the rat pituitary, NPFF is found exclusively in the neural lobe, where it is localized in nerve terminals and fibers, indicating the hypothalamus as a possible source of the neural lobe NPFF. In this study the origin of neurohypophyseal NPFF as investigated using various hypothalamic lesions and an anterograde tracing experiment. The results suggest that at least part of the neurohypophyseal NPFF originates from the supraoptic nucleus and may be localized in some of the arginine vasopressin-containing magnocellular neurons. C1 NIMH, ST ELIZABETHS HOSP, CTR NEUROSCI, BIOCHEM GENET LAB, WASHINGTON, DC 20032 USA. UNIV HELSINKI, DEPT ANAT, SF-00014 HELSINKI, FINLAND. ABO AKAD UNIV, DEPT BIOL, SF-20520 TURKU, FINLAND. NR 35 TC 28 Z9 28 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1993 VL 133 IS 4 BP 1578 EP 1584 DI 10.1210/en.133.4.1578 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MA411 UT WOS:A1993MA41100013 PM 8404597 ER PT J AU GALA, RR SHEVACH, EM AF GALA, RR SHEVACH, EM TI IDENTIFICATION BY ANALYTICAL FLOW-CYTOMETRY OF PROLACTIN RECEPTORS ON IMMUNOCOMPETENT CELL-POPULATIONS IN THE MOUSE SO ENDOCRINOLOGY LA English DT Article ID HUMAN THYMOCYTES; GENE-EXPRESSION; CONCANAVALIN-A; LYMPHOID-CELLS; LYMPHOCYTES; RAT; ANTIBODIES; LINE; PROLIFERATION; CYCLOSPORINE AB Five monoclonal antibodies (T1, T6, U5, U6, and E21) made to the external portion of the rat PRL receptor (PRL-R) were conjugated to fluorescein isothyrocynate and used to examine the presence of PRL-R on mouse lymphocytes and macrophages using analytical flow cytometry. The monoclonals were initially evaluated using Nb2 cells, a cloned line from a rat lymphoma, and NOG-8 cells, a cloned line from normal mouse mammary gland tissue, which are known to have PRL-R. All monoclonal antibodies bound to these cells, but the U5 monoclonal gave the best separation from unstained cells. CTLL-2 cells, a mouse lymphoma cell line containing interleukin-2 receptors, did not bind to any of the monoclonals. Isolated thioglycolate-induced peritoneal macrophages contained PPL-R, and the PRL-R monoclonal U5 gave the best separation from unstained cells. Eighty-five percent of macrophages constitutively had PRL-R using this monoclonal. In vivo stimulation of the popliteal lymph node by the injection of Concanavalin-A (Con-A) into the right foot pad of intact and ovariectomized (OVX) BALB/c mice induced, at the end of 10-12 h, a marked increase in interleukin-2 receptor (IL-2R) expression on CD4, CD8, and B-cells compared to the unstimulated left popliteal lymph node. The number of CD4 and CD8 cells from OVX animals with IL-2R was twice that from intact animals, whereas no difference in the percentage of B-cells with IL-2R was evident. PRL-R were constitutively expressed on 5% of the CD4 cells and 20% of the CD8 cells and were increased in the Con-A-stimulated lymph node when examined with the U5 PRL-R monoclonal. A higher percentage of CD4 and CD8 cells from OVX animals constitutively expressed PRL-R, and when stimulated with Con-A, a further increase was observed compared to the level in intact animals. Using the U5 monoclonal, over 80% of the B220 cells constitutively expressed PRL-R; however, when Tl, T6, and U6 monoclonals were examined, the percentage was considerably below (20%) than that observed for U5. Con-A stimulation did not alter the percentage of B220 cells expressing PRL-R. These results show the importance of identifying lymphocyte subsets and examining a number of PRL-R monoclonals in determining lymphocyte PRL-R expression on the surface of the cell. C1 NIAID, IMMUNOL LAB, BETHESDA, MD 20892 USA. RP GALA, RR (reprint author), WAYNE STATE UNIV, SCH MED, DEPT PHYSIOL, 540 E CANFIELD AVE, DETROIT, MI 48201 USA. FU NCI NIH HHS [IPA CAN-2-8325806] NR 33 TC 54 Z9 54 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1993 VL 133 IS 4 BP 1617 EP 1623 DI 10.1210/en.133.4.1617 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MA411 UT WOS:A1993MA41100018 PM 8404602 ER PT J AU HAUGER, RL AGUILERA, G AF HAUGER, RL AGUILERA, G TI REGULATION OF PITUITARY CORTICOTROPIN-RELEASING HORMONE (CRH) RECEPTORS BY CRH - INTERACTION WITH VASOPRESSIN SO ENDOCRINOLOGY LA English DT Article ID STRESS ENHANCES VASOPRESSIN; MESSENGER-RNA REGULATION; MEDIAN-EMINENCE; WATER-DEPRIVATION; ADRENOCORTICOTROPIN SECRETION; PARAVENTRICULAR NUCLEUS; ARGININE VASOPRESSIN; HYPOTHALAMIC NUCLEI; OSMOTIC STIMULUS; EXTERNAL ZONE AB The physiological regulation of ACTH secretion is largely dependent on the interactive effects of CRH and vasopressin (VP) in the pituitary corticotroph. The importance of the magnocellular and parvicellular hypothalamic systems as a source of VP for pituitary regulation was studied by analyzing the effects of endogenous activation of these systems or VP infusion on the ability of CRH to regulate its receptor sites in the anterior pituitary. CRH receptors were measured by binding of [I-125]Tyr-ovine CRH to membrane-rich fractions of anterior and neurointermediate pituitary lobes. Minipump infusion of 100 ng/min CRH for 48 h caused a 40% decrease in the anterior pituitary CRH receptor concentration. Simultaneous infusion of VP markedly potentiated the effect of CRH, but only at doses that elevated plasma VP to levels in the range of those in the pituitary portal circulation. Activation of the magnocellular vasopressinergic system by 60 h of water deprivation increased plasma VP levels from 0.5 +/- 0.1 to 11.8 +/- 0.6 pg/ml, but had no effect on the anterior pituitary CRH receptor concentration in control rats or animals receiving CRH infusion (100 ng/min for 48 h). The CRH receptor concentration was significantly increased in neurointermediate pituitary membranes from water-deprived rats. When the parvicellular vasopressinergic system was activated by 14 days of repeated restraint stress, there was a significant enhancement in the ability of CRH to decrease anterior pituitary CRH receptors (33% and 62% in control and stressed rats, respectively). The concomitant infusion of 200 ng/min of the VP antagonist [(mercapto cyclopentamethylene propionic acid)-[methyl-tyrosine]arginine VP] during the CRH infusion in chronically stressed rats, significantly reduced the magnitude of the pituitary CRH receptor loss from a 62% to a 43% decrease (P < 0.01). In conclusion, exogenous VP modulates pituitary CRH receptor regulation by CRH only at doses sufficiently high to provide peripheral VP concentrations in the range of the circulating levels in hypophysial-portal blood. Furthermore, the demonstration that chronic endogenous activation of the parvicellular, but not the magnocellular, vasopressinergic system enhances the down-regulatory effect of CRH on anterior pituitary CRH receptors is in support of a critical role of parvicellular VP in the control of the corticotroph function. C1 NICHHD, DEV ENDOCRINOL BRANCH, ENDOCRINE PHYSIOL SECT, BETHESDA, MD 20892 USA. UNIV CALIF SAN DIEGO, VET AFFAIRS MED CTR, LA JOLLA, CA 92093 USA. UNIV CALIF SAN DIEGO, DEPT PSYCHIAT, LA JOLLA, CA 92093 USA. NR 53 TC 81 Z9 82 U1 1 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1993 VL 133 IS 4 BP 1708 EP 1714 DI 10.1210/en.133.4.1708 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MA411 UT WOS:A1993MA41100030 PM 8404613 ER PT J AU ELLIOT, SJ STRIKER, LJ HATTORI, M YANG, CW HE, CJ PETEN, EP STRIKER, GE AF ELLIOT, SJ STRIKER, LJ HATTORI, M YANG, CW HE, CJ PETEN, EP STRIKER, GE TI MESANGIAL CELLS FROM DIABETIC NOD MICE CONSTITUTIVELY SECRETE INCREASED AMOUNTS OF INSULIN-LIKE GROWTH FACTOR-I SO ENDOCRINOLOGY LA English DT Article ID SOMATOMEDIN-C; IGF-I; BINDING; KIDNEY; RECEPTORS; MOUSE; RAT; NEPHROPATHY; FIBROBLASTS; MECHANISM AB Experimental evidence has suggested that insulin-like growth factor-I (IGF-I) may contribute to diabetic complications. Previously, we and others have shown that normal glomerular mesangial cells have receptors for, synthesize, and exhibit a mitogenic response to IGF-I. We investigated the IGF-I response in cells derived from a genetic model of diabetes, the nonobese diabetic (NOD) mouse. Mesangial cell lines were derived from diabetic (D-NOD) and nondiabetic adult mice. D-NOD cells released more IGF-I into the supernatant and had a decreased binding of IGF-I to surface receptors. Analysis according to Scatchard revealed a decreased number of receptor sites on D-NOD cells, although the structure of the IGF-I receptor visualized by crosslinking was identical for both cell types. Preincubation of D-NOD cells with an antibody to IGF-I resulted in an increase in the number of receptor sites. This suggested that autocrine IGF-I was responsible for the decrease in D-NOD receptor number and that diabetes had resulted in a stable phenotypic change. C1 NIDDKD, METAB DIS BRANCH,RENAL CELL BIOL SECT,BLDG 10, ROOM 3N110,9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. JOSLIN DIABET CTR, BOSTON, MA 02215 USA. FU NIDDK NIH HHS [P30 RO1DK-43613, DK-36836] NR 27 TC 44 Z9 45 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1993 VL 133 IS 4 BP 1783 EP 1788 DI 10.1210/en.133.4.1783 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MA411 UT WOS:A1993MA41100040 PM 7691581 ER PT J AU LEVYTOLEDANO, R CARO, LHP HINDMAN, N TAYLOR, SI AF LEVYTOLEDANO, R CARO, LHP HINDMAN, N TAYLOR, SI TI STREPTAVIDIN BLOTTING - A SENSITIVE TECHNIQUE TO STUDY CELL-SURFACE PROTEINS - APPLICATION TO INVESTIGATE AUTOPHOSPHORYLATION AND ENDOCYTOSIS OF BIOTIN-LABELED INSULIN-RECEPTORS SO ENDOCRINOLOGY LA English DT Article ID TRANSPORT; ANTIBODIES; SUBUNIT AB Covalent attachment of biotin provides a useful method to label cell surface proteins. Subsequent to biotinylation, the protein can be purified by immunoprecipitation with a specific antibody, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. After transfer to a membrane by electroblotting, the biotinylated protein can be detected by probing with labeled streptavidin. This technique has been used to investigate recombinant human insulin receptors expressed on the surface of murine NIH-3T3 cells. Biotinylation of the extracellular domain with an impermeant reagent did not impair the ability of an antibody directed against an epitope in the intracellular domain to immunoprecipitate insulin receptors. In contrast, biotinylation reduced the avidity of a polyclonal antibody directed against the extracellular domain of the receptor. Nevertheless, by increasing the concentration of the antireceptor antibody, it was possible to successfully immunoprecipitate the biotinylated receptor. Furthermore, biotinylated receptors retained the ability to bind insulin and undergo insulin-stimulated autophosphorylation and internalization. The use of enzyme-labeled streptavidin enables the use of chemiluminescence techniques to detect the receptors, thus obviating the need to employ radioactivity. Just as the technique is useful to study cell surface insulin receptors, it can be adapted to investigate other cell surface receptors and proteins. C1 NIDDKD, DIABET BRANCH, BLDG 10, ROOM 85-239, BETHESDA, MD 20892 USA. NR 12 TC 54 Z9 54 U1 1 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1993 VL 133 IS 4 BP 1803 EP 1808 DI 10.1210/en.133.4.1803 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MA411 UT WOS:A1993MA41100043 PM 8404622 ER PT J AU PLAUT, K IKEDA, M VONDERHAAR, BK AF PLAUT, K IKEDA, M VONDERHAAR, BK TI ROLE OF GROWTH-HORMONE AND INSULIN-LIKE GROWTH FACTOR-I IN MAMMARY DEVELOPMENT SO ENDOCRINOLOGY LA English DT Article ID MESSENGER-RNA; BOVINE SOMATOTROPIN; GLUCOSE-TRANSPORT; EPITHELIAL-CELLS; GLAND; EXPRESSION; PROTEIN AB Mammary glands from 3- to 4-week-old mice were incubated in whole organ culture to determine the effects of GH, PRL, and insulin-like growth factor-I (IGF-I) on lobulo-alveolar development and milk protein expression. Virgin mice were implanted with pellets of estrogen and progesterone (1:1000). After 9 days, abdominal no. 4 glands were removed and place on siliconized lens paper in Waymouths' medium supplemented with insulin (Ins), aldosterone, hydrocortisone, and epidermal growth factor. Concentrations of bovine GH, ovine GH, rat GH, or ovine PRL added to the medium varied from 0-1 mug/ml. IGF-I was added to replace either Ins or PRL up to 1 mug/ml. When glands were incubated with Ins, aldosterone, hydrocortisone, and 250 ng/ml PRL, they exhibited lobulo-alveolar development and expressed the milk protein beta-casein. When GH was substituted for PRL, little lobulo-alveolar development occurred, although beta-casein mRNA was expressed at low levels. Either PRL or GH at 1 mug/ml induced lobulo-alveolar development and beta-casein mRNA. Addition of epidermal growth factor to whole organ culture with GH or PRL (1 mug/ml) was equally effective in stimulating lobulo-alveolar development. IGF-I did not substitute for PRL, GH, or insulin in tissue maintenance. It is clear that GH at high concentrations can act directly on mouse mammary tissue to induce both lobulo-alveolar development and casein expression. C1 NCI, TUMOR IMMUNOL & BIOL LAB, BLDG 10, ROOM 5B56, BETHESDA, MD 20892 USA. NCI, DEPT ANIM & FOOD SCI, BETHESDA, MD 20892 USA. NR 34 TC 64 Z9 65 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1993 VL 133 IS 4 BP 1843 EP 1848 DI 10.1210/en.133.4.1843 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MA411 UT WOS:A1993MA41100048 PM 8404627 ER PT J AU OSTROWSKI, NL YOUNG, WS KNEPPER, MA LOLAIT, SJ AF OSTROWSKI, NL YOUNG, WS KNEPPER, MA LOLAIT, SJ TI EXPRESSION OF VASOPRESSIN V1A AND V2 RECEPTOR MESSENGER-RIBONUCLEIC-ACID IN THE LIVER AND KIDNEY OF EMBRYONIC, DEVELOPING, AND ADULT-RATS SO ENDOCRINOLOGY LA English DT Article ID ADENYLATE-CYCLASE ACTIVATION; ARGININE VASOPRESSIN; BINDING-SITES; AUTORADIOGRAPHIC LOCALIZATION; HORMONAL BINDING; OXYTOCIN; BRAIN; ONTOGENESIS; PITUITARY; CLONING AB The ontogenic expression of mRNAs encoding the V1a and V2 vasopressin receptors (V1aR and V2R) was visualized in liver and kidney of embryonic, developing, and adult rats using in situ hybridization histochemistry. Transcripts were detected at 16 and 19 days gestational age in kidney, with V1aR mRNA predominating in the developing cortex and V2R in the medulla. V1aR transcripts in 1-day-old kidneys were in vascular elements, in cells of developing medullary collecting ducts, and over mesangial cells of deep glomeruli, consistent with a role for the V1aR in regulating cellular growth. Expression of V1aR mRNA in the adult was found mainly in medullary vascular elements, arcuate and interlobular arteries, short segments of the cortical distal tubule, and transitional epithelium and smooth muscle of the pelvic wall and ureter. V2R mRNA, at 16 and 19 days gestational age, was in cells of developing medullary and cortical collecting ducts and, after birth, in cells of differentiating thick limbs of the loops of Henle, papillary surface epithelium, overlying macula densa, and short distal nephron segments. This distribution is in accord with the known role of V2 receptors in regulating water excretion. In contrast to kidney, liver did not express V2R mRNA and expressed V1aR transcripts only after birth. V1aR mRNA labeling was over cells bordering central veins on day 1 and surrounding central veins by day 5. A gradient was maximal on postnatal day 21, with V1aR mRNA most abundant in hepatocytes surrounding central veins and virtually absent in periportal hepatocytes. By day 60, most hepatocytes expressed V1aR transcripts, and the gradient was reduced. The ontogenic expression and receptor mRNA gradient are consistent with a role for hepatic V1a receptors in glucoregulation. These experiments confirm the presence of both Via and V2 receptors in kidney and show that vasopressin receptor mRNA expression is developmentally regulated and tissue specific. C1 NHLBI, KIDNEY & ELECTROLYTE METAB LAB, BETHESDA, MD 20892 USA. RP OSTROWSKI, NL (reprint author), NIMH, CELL BIOL LAB, BLDG 36, ROOM 2D-10, BETHESDA, MD 20892 USA. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 NR 35 TC 115 Z9 118 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1993 VL 133 IS 4 BP 1849 EP 1859 DI 10.1210/en.133.4.1849 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MA411 UT WOS:A1993MA41100049 PM 8404628 ER PT J AU JACOBSONKRAM, D ALBERTINI, RJ BRANDA, RF FALTA, MT IYPE, PT KOLODNER, K LIOU, SH MCDIARMID, MA MORRIS, M NICKLAS, JA ONEILL, JP POIRIER, MC PUTMAN, D STRICKLAND, PT WILLIAMS, JR XIAO, SQ AF JACOBSONKRAM, D ALBERTINI, RJ BRANDA, RF FALTA, MT IYPE, PT KOLODNER, K LIOU, SH MCDIARMID, MA MORRIS, M NICKLAS, JA ONEILL, JP POIRIER, MC PUTMAN, D STRICKLAND, PT WILLIAMS, JR XIAO, SQ TI MEASUREMENT OF CHROMOSOMAL-ABERRATIONS, SISTER-CHROMATID EXCHANGE, HPRT MUTATIONS, AND DNA-ADDUCTS IN PERIPHERAL LYMPHOCYTES OF HUMAN-POPULATIONS AT INCREASED RISK FOR CANCER SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID BASE-LINE; CYCLOPHOSPHAMIDE AB Using a multidisciplinary approach, we have measured various indicators of DNA damage in peripheral lymphocytes of human populations potentially at increased risk for cancer. Sister chromatid exchanges (SCE) and polycyclic aromatic hydrocarbon (PAH)-DNA adducts were evaluated in a group of firefighters; chromosomal aberrations and hprt mutations were evaluated in a group of cancer patients undergoing radioimmunoglobulin therapy (RIT); SCE and acrolein-modified DNA were measured in cancer chemotherapy patients and in pharmacists preparing chemotherapy prescriptions; and SCE and PAH-DNA adducts are being measured in U.S. army troops stationed in Kuwait. Our results indicate that both SCE and PAH-DNA adduct levels were not elevated in firefighters, but that other factors such as smoking status and race were risk factors for increased SCE and PAH-DNA adducts. RIT was found to increase background rates of chromosome-type aberrations and frequencies of hprt mutations and there was a strong correlation between levels of therapy-induced chromosome damage sustained in vivo and in vitro sensitivity to radiation-induced chromosome damage. Peripheral blood lymphocytes of cancer patients treated with cyclophosphamide showed higher levels of SCE and had a higher incidence of acrolein adducts in DNA. Lymphocytes from pharmacists preparing antineoplastic drugs were found to acquire increased in vitro sensitivity to SCE induction by phosphoramide mustard with increased lifetime duration of drug handling. A prospective, longitudinal study was performed to identify environmental factors that modulate genetic damage in breast cancer patients. Women with benign breast masses and no apparent disease served as controls. Mutant frequency, cloning efficiency, and chromosomal aberration frequency did not differ significantly among the three groups. The results described and the data being gathered on troops stationed in Kuwait suggest that all the methodologies described can be useful in screening human populations for mutagenic exposures. C1 BIOL RES FAC & FACIL INC,IJAMSVILLE,MD 21754. UNIV VERMONT,VERMONT REG CANC CTR,BURLINGTON,VT 05401. UNIV VERMONT,DEPT MED,GENET LAB,BURLINGTON,VT 05401. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD 21205. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,RADIOBIOL LAB,BALTIMORE,MD 21205. RP JACOBSONKRAM, D (reprint author), MICROBIOL ASSOCIATES INC,TOXICOL GRP,ROCKVILLE,MD 20850, USA. RI Liou, Saou-Hsing /B-2667-2010 NR 10 TC 22 Z9 22 U1 1 U2 4 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 1993 VL 101 SU 3 BP 121 EP 125 DI 10.2307/3431712 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA MN668 UT WOS:A1993MN66800023 PM 8143603 ER PT J AU TENNANT, RW AF TENNANT, RW TI A PERSPECTIVE ON NONMUTAGENIC MECHANISMS IN CARCINOGENESIS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID F344/N RATS; CORN-OIL; CANCER; ORIGIN; MICE AB Although there is compelling evidence for multiple mutagenic events in the induction of cancers, there is also substantial evidence in support of nonmutagenic mechanisms. It is proposed that the genetic basis of noninduced or spontaneous tumors, as well as cancers induced by nonmutagens, involves heritable changes in the regulation of gene expression. RP TENNANT, RW (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 24 TC 14 Z9 14 U1 0 U2 1 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 1993 VL 101 SU 3 BP 231 EP 236 DI 10.2307/3431731 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA MN668 UT WOS:A1993MN66800042 PM 8143623 ER PT J AU MCLACHLAN, JA AF MCLACHLAN, JA TI FUNCTIONAL TOXICOLOGY - A NEW APPROACH TO DETECT BIOLOGICALLY-ACTIVE XENOBIOTICS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE ESTROGENS; FUNCTIONAL TOXICOLOGY; HORMONE RECEPTORS; XENOBIOTICS AB The pervasiveness of chemicals in the enviroment with estrogenic activity and other biological functions recommends the development of new approaches to monitor and study them. Chemicals can be screened for activity in vitro using a panel of human or animal cells that have been transfected with a specific receptor and reporter gene; for example, the estrogen receptor. By using a variety of different receptors, the screening of xenobiotics for biological functions can be broad. Chemicals could then be classified by their function in vitro which, in some cases, may be a useful guide for toxicological studies. RP MCLACHLAN, JA (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 13 TC 184 Z9 188 U1 1 U2 4 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 1993 VL 101 IS 5 BP 386 EP 387 DI 10.2307/3431891 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA MJ118 UT WOS:A1993MJ11800006 PM 8119246 ER PT J AU WACHSMAN, JT BRISTOL, DW SPALDING, J SHELBY, M TENNANT, RW AF WACHSMAN, JT BRISTOL, DW SPALDING, J SHELBY, M TENNANT, RW TI PREDICTING CHEMICAL CARCINOGENESIS IN RODENTS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material ID NATIONAL-TOXICOLOGY-PROGRAM; 44 CHEMICALS; BIOASSAYS; SET RP WACHSMAN, JT (reprint author), NIEHS, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 8 TC 8 Z9 8 U1 0 U2 3 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 1993 VL 101 IS 5 BP 444 EP 445 DI 10.2307/3431903 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA MJ118 UT WOS:A1993MJ11800016 PM 8119256 ER PT J AU WAGENKNECHT, LE MANOLIO, TA SIDNEY, S BURKE, GL HALEY, NJ AF WAGENKNECHT, LE MANOLIO, TA SIDNEY, S BURKE, GL HALEY, NJ TI ENVIRONMENTAL TOBACCO-SMOKE EXPOSURE AS DETERMINED BY COTININE IN BLACK-AND-WHITE YOUNG-ADULTS - THE CARDIA STUDY SO ENVIRONMENTAL RESEARCH LA English DT Article ID SERUM COTININE; BIOCHEMICAL VALIDATION; CIGARETTE-SMOKING; PASSIVE SMOKING; CHILDREN; BEHAVIOR C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. KAISER PERMANENTE MED CARE PROGRAM,DIV RES,OAKLAND,CA 94611. METROPOLITAN LIFE INSURANCE CO,INSURANCE TESTING LAB,ELMSFORD,NY 10523. RP WAGENKNECHT, LE (reprint author), BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27157, USA. FU NHLBI NIH HHS [NHLBI N01-HC-48047, NHLBI N01-HC-48048, NHLBI N01-HC-48049] NR 24 TC 37 Z9 39 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD OCT PY 1993 VL 63 IS 1 BP 39 EP 46 DI 10.1006/enrs.1993.1124 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA MA406 UT WOS:A1993MA40600004 PM 8404773 ER PT J AU MOCK, B BLACKWELL, J HILGERS, J POTTER, M NACY, C AF MOCK, B BLACKWELL, J HILGERS, J POTTER, M NACY, C TI GENETIC-CONTROL OF LEISHMANIA-MAJOR INFECTION IN CONGENIC, RECOMBINANT INBRED AND F2 POPULATIONS OF MICE SO EUROPEAN JOURNAL OF IMMUNOGENETICS LA English DT Article ID CUTANEOUS LEISHMANIASIS; HISTOCOMPATIBILITY; SUSCEPTIBILITY; TROPICA; STRAINS; LOCI AB The outcome of subcutaneous infection with L. major NIH 173 was evaluated in a series of recombinant inbred and congenic strains, as well as F2 progeny generated from a genetic linkage testing stock carrying the visible markers Ra, Os, and Pt. The disease parameters monitored were the incidence of open or necrotic lesions and footpad depths of infected feet, and the incidence and number of amastigotes in livers following infection. Regions of mouse chromosomes 2, 4, 7, 8, 12 and 15 were excluded from linkage to a gene (Scl-1) involved in the susceptibility of inbred strains of mice to cutaneous infection with L. major NIH 173 by F2 and congenic strain analyses. Strain distribution patterns generated for Scl-1 in the CXB and CXS recombinant inbred strains suggested linkage to the distal end of mouse Chromosome 11. C1 UNIV CAMBRIDGE,SCH CLIN,DEPT MED,CAMBRIDGE,ENGLAND. FREE UNIV AMSTERDAM,ACAD ZIEKENHUIS,DEPT OBSTET,1007 MC AMSTERDAM,NETHERLANDS. WALTER REED ARMY INST RES,DEPT CELLULAR IMMUNOL,WASHINGTON,DC 20307. RP MOCK, B (reprint author), NCI,GENET LAB,BLDG 37,ROOM 2B-08,BETHESDA,MD 20892, USA. RI Blackwell, Jenefer/H-3015-2015 NR 20 TC 42 Z9 42 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0960-7420 J9 EUR J IMMUNOGENET JI Eur. J. Immunogenet. PD OCT PY 1993 VL 20 IS 5 BP 335 EP 348 DI 10.1111/j.1744-313X.1993.tb00153.x PG 14 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA LZ761 UT WOS:A1993LZ76100003 PM 9098402 ER PT J AU ROBERTS, M MOCK, BA BLACKWELL, JM AF ROBERTS, M MOCK, BA BLACKWELL, JM TI MAPPING OF GENES-CONTROLLING LEISHMANIA-MAJOR INFECTION IN CXS RECOMBINANT INBRED MICE SO EUROPEAN JOURNAL OF IMMUNOGENETICS LA English DT Article ID MURINE CUTANEOUS LEISHMANIASIS; T-CELL SUBSETS; INTERFERON-GAMMA; DIFFERENTIAL REGULATION; CYTOKINE FAMILY; BALB/C MICE; EXPRESSION; SUSCEPTIBILITY; CHROMOSOME-11; RESISTANCE AB Previous studies demonstrated that growth of the primary lesion following Leishmania major infection in inbred mice comes under the control of a single major gene designated Scl-1. Preliminary mapping studies had suggested a chromosome 8 location for the gene. In this paper a more detailed study of different disease phenotypes (lesion growth, splenomegaly, liver parasite load) in 14 CXS recombinant inbred (RI) mouse strains was undertaken in order to obtain a more definitive map location for the gene. Using the Kruskal-Wallis generalization of the Wilcoxon Rank-Sum Test to assign RI strains to parental phenotypes, high concordances with genes at the mid (Il-3) to distal end (Dlb-1, Hox-2, Sigje, Mtv-3 and Es-3) of chromosome 11 were demonstrated with two strains (LV39 and NIH173) of L. major given as promastigotes subcutaneously into the shaven rump. The results suggest that the most likely location for the previously described single major gene (Scl-1) regulating early lesion expansion is at the distal end of mouse chromosome 11, with the possibility that a gene located more proximally influences later phases of the infection. C1 UNIV CAMBRIDGE,ADDENBROOKES HOSP,SCH CLIN,DEPT MED,LEVEL 4,HILLS RD,CAMBRIDGE CB2 2QQ,ENGLAND. UNIV CAMBRIDGE,DEPT PATHOL,CAMBRIDGE,ENGLAND. NCI,GENET LAB,BETHESDA,MD 20892. RI Blackwell, Jenefer/H-3015-2015 FU Wellcome Trust NR 36 TC 49 Z9 50 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0960-7420 J9 EUR J IMMUNOGENET JI Eur. J. Immunogenet. PD OCT PY 1993 VL 20 IS 5 BP 349 EP 362 DI 10.1111/j.1744-313X.1993.tb00154.x PG 14 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA LZ761 UT WOS:A1993LZ76100004 PM 9098403 ER PT J AU HILBERT, DM HOLMES, KL ANDERSON, AO RUDIKOFF, S AF HILBERT, DM HOLMES, KL ANDERSON, AO RUDIKOFF, S TI LONG-TERM THYMIC RECONSTITUTION BY PERIPHERAL CD4 AND CD8 SINGLE-POSITIVE LYMPHOCYTES SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE THYMIC IMMIGRATION; IN-VIVO LYMPHOCYTES HOMING; PEYER PATCHES; FLOW CYTOMETRY ID ACTIVATED T-CELLS; MONOCLONAL-ANTIBODIES; LINE CELLS; B-CELLS; MICE; MOUSE; RECEPTOR; EXPRESSION; ANTIGENS; THYMOCYTES AB Significant immigration of peripheral T cells into SCID thymus was observed following reconstitution with normal Peyer's patch, mesenteric lymph node or peripheral lymph node cells. Immunohistologic and flow cytometric analyses reveal that T cells from these tissues are found in the thymus for as long as 177 days and can account for up to 67% of intrathymic cells. The returning cells express the CD3/T cell receptor alpha/beta complex, indicative of mature cells, and are equally divided among helper (CD4+CD8-) and cytotoxic (CD4-/CD8+) phenotypes. The immigration of peripheral T cells is not accompanied by the appearance of immature, double-positive (CD4+CD8+) thymocytes as seen in similar reconstitutions using bone marrow. Taken together, these results suggest that peripheral T cells from a variety of lymphoid organs may regularly re-enter the thymus and, thus, possibly play a role in normal thymic development. C1 NIAID,BIOL RESOURCES BRANCH,FLOW CYTOMETRY SECT,BETHESDA,MD 20892. USA,MED RES INST INFECT DIS,DEPT RESP & MUCOSAL IMMUNOL,FREDERICK,MD 21701. RP HILBERT, DM (reprint author), NCI,GENET LAB,BETHESDA,MD 20892, USA. NR 40 TC 15 Z9 15 U1 0 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 1993 VL 23 IS 10 BP 2412 EP 2418 DI 10.1002/eji.1830231006 PG 7 WC Immunology SC Immunology GA MD626 UT WOS:A1993MD62600005 PM 8405041 ER PT J AU DENT, AL MATIS, LA BLUESTONE, JA HEDRICK, SM AF DENT, AL MATIS, LA BLUESTONE, JA HEDRICK, SM TI EVIDENCE FOR PROGRAMMED CELL-DEATH OF SELF-REACTIVE GAMMA-DELTA T-CELL RECEPTOR-POSITIVE THYMOCYTES SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE GAMMA-DELTA T-CELLS; TOLERANCE; DELETION; APOPTOSIS ID MAJOR HISTOCOMPATIBILITY COMPLEX; NEONATALLY THYMECTOMIZED MICE; MONOCLONAL-ANTIBODY; TRANSGENIC MICE; ANTIGEN RECEPTOR; APOPTOSIS; TOLERANCE; REPERTOIRE; RECOGNITION; THYMUS AB The negative selection of T cells expressing the gammadelta cell antigen receptor (gammadelta T cells) was studied using transgenic mice expressing a gammadelta receptor with specificity for an H-2T-linked class I major histocompatibility complex molecule from H-2b mice. The potentially self-reactive gammadelta thymocytes in H-2b/d transgenic mice are larger and have lower levels of gammadelta T cell receptor expression than gammadelta thymocytes from H-2d mice. H-2b/d gammadelta thymocytes do not respond to H-2b antigen-presenting cells, and thus are inactive compared to H-2d gammadelta thymocytes. However, the H-2bd gammadelta thymocyte population, but not the H-2d gammadelta thymocyte population, undergoes a high rate of programmed cell death when placed in overnight culture. These observations constitute the first direct evidence that self-reactive gammadelta thymocytes undergo programmed cell death. This in vitro programmed cell death of self-reactive gammadelta thymocytes may reflect the clonal deletion process that results in a depletion of gammadelta T cells in the peripheral lymphoid organs of adult H-2b/d mice. We also present evidence that self-reactive gammadelta T cells, similarly to alphabeta T cells, undergo a lesser degree of clonal deletion in neonatal mice compared to adult mice. C1 UNIV CALIF SAN DIEGO,DEPT BIOL,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,CTR CANC,LA JOLLA,CA 92093. NCI,MOLEC IMMUNOREGULAT LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. UNIV CHICAGO,BEN MAY INST,CHICAGO,IL 60637. FU NIAID NIH HHS [AI 23287-06, AI 26847-03] NR 44 TC 16 Z9 16 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 1993 VL 23 IS 10 BP 2482 EP 2487 DI 10.1002/eji.1830231016 PG 6 WC Immunology SC Immunology GA MD626 UT WOS:A1993MD62600015 PM 8405049 ER PT J AU KAISER, E FORSTER, R WOLF, I EBENSPERGER, C KUEHL, WM LIPP, M AF KAISER, E FORSTER, R WOLF, I EBENSPERGER, C KUEHL, WM LIPP, M TI THE G-PROTEIN-COUPLED RECEPTOR BLR1 IS INVOLVED IN MURINE B-CELL DIFFERENTIATION AND IS ALSO EXPRESSED IN NEURONAL TISSUES SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE B-CELL DIFFERENTIATION; G-PROTEIN-COUPLED RECEPTOR; CYTOKINE RECEPTOR; NEUROPEPTIDE RECEPTOR; BURKITTS LYMPHOMA ID HUMAN INTERLEUKIN-8 RECEPTOR; HUMAN T-CELLS; MESSENGER-RNA; FUNCTIONAL EXPRESSION; INSITU HYBRIDIZATION; SIGNAL TRANSDUCTION; BURKITTS-LYMPHOMA; ANTIGEN RECEPTOR; CYTOKINE FAMILY; CDNA AB The BLR1 gene, isolated initially from Burkitt's lymphoma cells (Eur. J Immunol. 1992. 22:2795), encodes a G protein-coupled receptor with significant relationship to receptors for chemokines (IL-8, MIP-1a) and neuropeptides. The murine homologue of human BLR1 was cloned and used to investigate its expression in vivo. blr1-specific transcripts are observed in secondary lymphatic organs and to a lesser extent in brain of adult mice but not in other tissues. RNA in situ hybridization localizes blr1 transcription to primary follicles and to the mantle zone of secondary follicles. SCID mice in which mature B cell development is severely impaired exhibit a strongly reduced level of blr1-specific RNA in the spleen. The analysis of murine lymphoid tumor cell lines representing distinct stages of the B cell lineage reveals elevated expression of blr1 in B cell lymphomas but not in pre-B lymphomas or plasmacytomas. Induction of differentiation of resting B cells by cytokines or mitogens down-regulates expression of blr1. RNA in situ hybridization using brain sections of adult mice detects blr1 transcription in the granule and Purkinje cell layer of the cerebellum. Interestingly, the blr1 gene is also expressed during late embryogenesis in fetal liver and brain. In view of the remarkable expression pattern in the B cell lineage we suggest that murine BLR1 may represent a cytokine/neuropeptide receptor exerting regulatory functions on recirculating mature B lymphocytes. C1 UNIV MUNICH,INST BIOCHEM,KLOPFERSPITZ 18A,D-82152 MARTINSRIED,GERMANY. UNIV ULM,KLIN GENET ABT,W-7900 ULM,GERMANY. USN,NCI,MED ONCOL BRANCH,BETHESDA,MD 20814. RI Lipp, Martin/G-2235-2010; Forster, Reinhold/D-6770-2011 NR 51 TC 52 Z9 53 U1 0 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 1993 VL 23 IS 10 BP 2532 EP 2539 DI 10.1002/eji.1830231023 PG 8 WC Immunology SC Immunology GA MD626 UT WOS:A1993MD62600022 PM 8405054 ER PT J AU GOODWIN, RG DIN, WS DAVISSMITH, T ANDERSON, DM GIMPEL, SD SATO, TA MALISZEWSKI, CR BRANNAN, CI COPELAND, NG JENKINS, NA FARRAH, T ARMITAGE, RJ FANSLOW, WC SMITH, CA AF GOODWIN, RG DIN, WS DAVISSMITH, T ANDERSON, DM GIMPEL, SD SATO, TA MALISZEWSKI, CR BRANNAN, CI COPELAND, NG JENKINS, NA FARRAH, T ARMITAGE, RJ FANSLOW, WC SMITH, CA TI MOLECULAR-CLONING OF A LIGAND FOR THE INDUCIBLE T-CELL GENE 4-1BB - A MEMBER OF AN EMERGING FAMILY OF CYTOKINES WITH HOMOLOGY TO TUMOR-NECROSIS-FACTOR SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE MURINE 4-1BB LIGAND; TYPE-II PROTEIN ID NERVE GROWTH-FACTOR; COLONY-STIMULATING FACTOR; PROTEIN-TYROSINE KINASE; FACTOR RECEPTOR GENE; EXPRESSION CLONING; IL-1 RECEPTOR; B-CELLS; ANTIGEN; CDNA; RESOLUTION AB 4-1BB is an inducible T cell antigen that shows sequence homology to members of an emerging family of cytokine receptors, including those for tumor necrosis factor and nerve growth factor. To aid in the analysis of the function of 4-1BB we have utilized a soluble form of the molecule as a probe to identify and clone the gene which encodes its ligand. The ligand for 4-1BB is a type II membrane glycoprotein that has homology to tumor necrosis factor, lymphotoxin, and the ligands for CD40 and CD27, all of which are themselves ligands to receptors in this superfamily. The gene for 4-1BB is on mouse chromosome 4 and maps close to the p80 form of the tumor necrosis factor receptor as well as the gene for CD30. The gene for 4-1BB ligand maps to mouse chromosome 17, but considerably distal to the tumor necrosis factor and lymphotoxin genes. Interaction of 4-1BB with its ligand induces the proliferation of activated thymocytes and splenic T cells, a response which is mimicked on similar cell populations stimulated with an antibody to 4-1BB. C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. RP GOODWIN, RG (reprint author), IMMUNEX RES & DEV CORP,51 UNIV ST,SEATTLE,WA 98101, USA. FU NCI NIH HHS [N01-CO-74101] NR 61 TC 233 Z9 252 U1 2 U2 6 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 1993 VL 23 IS 10 BP 2631 EP 2641 DI 10.1002/eji.1830231037 PG 11 WC Immunology SC Immunology GA MD626 UT WOS:A1993MD62600036 PM 8405064 ER PT J AU LEE, CH WASOWICZ, K BROWN, R MAJANE, EA YANG, HYT PANULA, P AF LEE, CH WASOWICZ, K BROWN, R MAJANE, EA YANG, HYT PANULA, P TI DISTRIBUTION AND CHARACTERIZATION OF NEUROPEPTIDE FF-LIKE IMMUNOREACTIVITY IN THE RAT NERVOUS-SYSTEM WITH A MONOCLONAL-ANTIBODY SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE NEUROPEPTIDE-FF; HYPOTHALAMUS; NUCLEUS OF THE SOLITARY TRACT; ANALGESIA; MORPHINE ID MORPHINE-MODULATING PEPTIDES; MAMMALIAN FMRF-NH2-LIKE PEPTIDE; SPINAL-CORD; BRAIN; FLFQPQRFAMIDE; FMRFAMIDE; FLFQPQRF-NH2; ANTISERUM; NEURONS; AMIDE AB Monoclonal antibodies against neuropeptide FF were produced and characterized. The antibodies are directed and highly specific to neuropeptide FF, and reactivity requires the C-terminal dipeptide of neuropeptide FF (Arg-Phe-NH2). Tissue extracts from bovine spinal cord, rat spinal cord and hypothalamus were analysed by high-pressure liquid chromatography coupled with radioimmunoassay using the characterized monoclonal antibody. Only one immunoreactive peptide was detected and it coeluted with authentic neuropeptide FF. Using this highly specific monoclonal antibody, the distribution of neuropeptide FF-like immunoreactivity was further studied by indirect immunohistochemistry. Immunoreactivity was seen in two major cell groups in the rat brain. The largest cell group was located in the medial hypothalamus between the dorsomedial and ventromedial nuclei. The other one was found in the nucleus of the solitary tract. Fibres immunoreactive for neuropeptide FF were located in the lateral septal nucleus, amygdala, different hypothalamic areas, nucleus of the solitary tract, ventral medulla, trigeminal complex and the dorsal horn of the spinal cord. Spinal and sympathetic ganglia were non-reactive. No neuropeptide FF immunoreactivity was seen in the gut autonomic nervous system or endocrine cells. The results show that neuropeptide FF-like immunoreactivity has a clearly more limited distribution in the nervous system than typical brain - gut peptides. C1 UNIV TURKU, ABO AKAD, DEPT BIOL, BIOCITY, TYKISTOKATU 6A, SF-20520 TURKU 52, FINLAND. USN, MED RES INST, CASUALTY CARE RES DEPT, DIV METAB RES, BETHESDA, MD 20814 USA. NIMH, NEUROSCI CTR ST ELIZABETH, BIOCHEM GENET LAB, WASHINGTON, DC 20032 USA. UNIV HELSINKI, DEPT ANAT, SF-00014 HELSINKI, FINLAND. NR 25 TC 33 Z9 33 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD OCT 1 PY 1993 VL 5 IS 10 BP 1339 EP 1348 DI 10.1111/j.1460-9568.1993.tb00920.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA MD752 UT WOS:A1993MD75200012 PM 8275233 ER PT J AU WELLER, M PAUL, SM AF WELLER, M PAUL, SM TI 3-NITROPROPIONIC ACID IS AN INDIRECT EXCITOTOXIN TO CULTURED CEREBELLAR GRANULE NEURONS SO EUROPEAN JOURNAL OF PHARMACOLOGY-ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY SECTION LA English DT Article DE 3-NITROPROPIONIC ACID; EXCITOTOXICITY; NMDA (N-METHYL-D-ASPARTATE); GLUTAMATE; CEREBELLAR GRANULE NEURONS ID D-ASPARTATE RECEPTOR; ENERGY-METABOLISM; BRAIN-LESIONS; CELLS; GLUTAMATE; TOXICITY; RATS; IMPAIRMENT AB The ability of N-methyl-D-aspartate (NMDA) receptor agonists and antagonists to modify 3-nitropropionic acid toxicity was studied in cultured rat cerebellar granule neurons. Exposure of these neurons to 3-nitropropionic acid resulted in a concentration and time-dependent neurotoxicity. In contrast to glutamate toxicity, 3-nitropropionic acid toxicity was potentiated by preexposure to subtoxic concentrations of NMDA. Presumably, the 3-nitropropionic acid-induced energy depletion relieved the voltage-dependent Mg2+ block of the NMDA receptor and induced vulnerability to subtoxic concentrations of NMDA receptor agonists. MK-801 and 2-amino-5-phosphonovaleric acid (APV) delayed but did not prevent 3-nitropropionic acid toxicity, indicating that prolonged exposure to 3-nitropropionic acid ultimately resulted in histotoxic neuronal death. We conclude that there are at least two distinct mechanisms of 3-nitropropionic acid toxicity of cerebellar granule neurons, one indirectly involving NMDA receptor-mediated excitotoxicity and one that is NMDA receptor-independent. C1 NIMH,CLIN NEUROSCI BRANCH,MOLEC PHARMACOL SECT,BETHESDA,MD 20892. NR 19 TC 36 Z9 36 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6917 J9 EUR J PHARM-ENVIRON JI Eur. J. Pharmacol.-Environ. Toxicol. Pharmacol. Sect. PD OCT 1 PY 1993 VL 248 IS 3 BP 223 EP 228 DI 10.1016/0926-6917(93)90048-U PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA ME089 UT WOS:A1993ME08900002 PM 7904944 ER PT J AU SCHMALIX, WA MASER, H KIEFER, F REEN, R WIEBEL, FJ GONZALEZ, F SEIDEL, A GLATT, H GREIM, H DOEHMER, J AF SCHMALIX, WA MASER, H KIEFER, F REEN, R WIEBEL, FJ GONZALEZ, F SEIDEL, A GLATT, H GREIM, H DOEHMER, J TI STABLE EXPRESSION OF HUMAN CYTOCHROME-P450 1A1 CDNA IN V79 CHINESE-HAMSTER CELLS AND METABOLIC-ACTIVATION OF BENZO[A]PYRENE SO EUROPEAN JOURNAL OF PHARMACOLOGY-ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY SECTION LA English DT Article DE CYTOCHROME P450 1A1 (HUMAN); CYTOCHROME P450 1A1 RECOMBINANT EXPRESSION VECTOR; V79 CHINESE HAMSTER CELLS; POLYCYCLIC AROMATIC HYDROCARBONS; BENZO[A]PYRENE ID POLYCYCLIC AROMATIC-HYDROCARBONS; LIVER-MICROSOMES; LUNG-CANCER; ELECTROPHORETIC TRANSFER; POLYACRYLAMIDE GELS; CYP1A1 GENE; RAT; INDUCTION; LINE; DNA AB A V79 Chinese hamster cell line stably expressing human cytochrome P450 1A1 (CYP1A1) was obtained by chromosomal integration of the human CYP1A1 cDNA under the control of the SV40 early promoter. Chromosomal integration was verified by Southern analysis, and effective transcription of the human CYP1A1 cDNA was demonstrated by Northern analysis. The CYP1A1 cDNA-encoded protein was characterized by Western analysis using anti-rat CYP1A1. Intracellular association of CYP1A1 with the endoplasmic reticulum could be visualized by in situ immunofluorescence. Crude cel lysates of the V79 derived cell line was able to catalyze 7-ethoxyresorufin-O-deethylation (EROD) with an activity of about 50 pmol min(-1) mg(-1) total protein, and an aryl hydrocarbon hydroxylase activity (AHH) of 25 pmol min(-1) mg(-1). CYP1A1 dependent cytotoxicity, measured by neutral red uptake, and genotoxicity, determined by the frequency of micronucleus formation, of benzo[a]pyrene (B[a]P) and trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (B[a]P-7,8-diol) could be demonstrated at substrate concentrations as low as 10 nM. Thus, this cell line presents a sensitive tool for studying CYP1A1 mediated metabolism of polycyclic aromatic hydrocarbons (PAH). B[a]P and the purified (+)- and (-)-enantiomers of B[a]P-7,8-diol were compared for their mutagenicity. The (-)-enantiomer was found to be 3-5-fold more mutagenic than the (+)-enantiomer. C1 TECH UNIV MUNICH,INST TOXIKOL & UMWELTHYG,D-80636 MUNICH,GERMANY. GSF MUNICH,FORSCHUNGSZENTUM UMWELT & GESUNDHEIT,INST TOXIKOL,D-85758 NEUHERBERG,GERMANY. REG RES LAB,JAMMU 180001,INDIA. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. UNIV MAINZ,INST TOXIKOL,D-55131 MAINZ,GERMANY. OI Glatt, Hansruedi/0000-0001-6053-0562 NR 70 TC 63 Z9 65 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6917 J9 EUR J PHARM-ENVIRON JI Eur. J. Pharmacol.-Environ. Toxicol. Pharmacol. Sect. PD OCT 1 PY 1993 VL 248 IS 3 BP 251 EP 261 DI 10.1016/0926-6917(93)90052-R PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA ME089 UT WOS:A1993ME08900006 PM 8293790 ER PT J AU OGISO, Y YOKOYAMA, T WATARI, H SHIH, TY KUZUMAKI, N AF OGISO, Y YOKOYAMA, T WATARI, H SHIH, TY KUZUMAKI, N TI RESISTANCE OF NIH3T3 CELLS TO V-FES TRANSFORMATION-INDUCED BY A DOMINANT-NEGATIVE H-RAS MUTANT SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID MITOGENIC SIGNAL TRANSDUCTION; FUJINAMI SARCOMA-VIRUS; GROWTH-FACTOR RECEPTOR; PROTEIN-KINASE-C; TYROSINE PHOSPHORYLATION; FLAT REVERTANTS; MUTATIONS; ONCOGENE; MEMBRANE; RAF-1 C1 NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702. RP OGISO, Y (reprint author), HOKKAIDO UNIV,SCH MED,CANC RECH INST,MOLEC GENET LAB,SAPPORO,HOKKAIDO 060,JAPAN. NR 41 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD OCT PY 1993 VL 208 IS 2 BP 415 EP 421 DI 10.1006/excr.1993.1263 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA MA098 UT WOS:A1993MA09800010 PM 7690710 ER PT J AU LAVER, NM ROBISON, WG CALVIN, HI FU, SCJ AF LAVER, NM ROBISON, WG CALVIN, HI FU, SCJ TI EARLY EPITHELIAL LESIONS IN CATARACTS OF GSH-DEPLETED MOUSE PUPS SO EXPERIMENTAL EYE RESEARCH LA English DT Letter ID BUTHIONINE SULFOXIMINE; VITAMIN-E; GLUTATHIONE; LENS; ASCORBATE; INHIBITION; METABOLISM; DEFICIENCY; ESTER C1 NEI,BLDG 6,ROOM 316,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. UNIV MED & DENT NEW JERSEY,DEPT BIOCHEM & MOLEC BIOL,NEWARK,NJ 07103. FU NEI NIH HHS [EY-07355] NR 16 TC 18 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD OCT PY 1993 VL 57 IS 4 BP 493 EP 498 DI 10.1006/exer.1993.1151 PG 6 WC Ophthalmology SC Ophthalmology GA ME081 UT WOS:A1993ME08100013 PM 8282035 ER PT J AU TAYLORBROWN, S WIENER, L AF TAYLORBROWN, S WIENER, L TI MAKING VIDEOTAPES OF HIV-INFECTED WOMEN FOR THEIR CHILDREN SO FAMILIES IN SOCIETY-THE JOURNAL OF CONTEMPORARY HUMAN SERVICES LA English DT Article ID THERAPY AB In the United States, the majority of HIV-infected women are of childbearing age and have dependent childen. Seropositivity for HIV threatens a woman's ability to care for her children into adulthood. In an effort to address the pain these women feel regarding their parental role, the authors helped HIV-infected women develop videotapes for their children. This article describes the therapeutic application of videotapes for HIV-infected women with dependent children. Case studies illustrate how women are prepared to make a tape for their children and the taping process as well as examine issues practitioners confront before, during, and after the taping session. C1 NCI,PEDIAT HIV PSYCHOSOCIAL SUPPORT PROGRAM,BETHESDA,MD 20892. RP TAYLORBROWN, S (reprint author), SYRACUSE UNIV,SCH SOCIAL WORK,SYRACUSE,NY 13244, USA. NR 16 TC 1 Z9 1 U1 0 U2 0 PU FAMILY SERVICE AMER PI MILWAUKEE PA 11700 WEST LAKE PARK DRIVE, MILWAUKEE, WI 53224 SN 1044-3894 J9 FAM SOC-J CONTEMP H JI Fam. Soc.-J. Contemp. Hum. Serv. PD OCT PY 1993 VL 74 IS 8 BP 468 EP 480 PG 13 WC Family Studies; Social Work SC Family Studies; Social Work GA MA240 UT WOS:A1993MA24000003 ER PT J AU LEVINE, RL AF LEVINE, RL TI ISCHEMIA - FROM ACIDOSIS TO OXIDATION SO FASEB JOURNAL LA English DT Review DE SHOCK; ACIDOSIS; ISCHEMIA; REPERFUSION INJURY; METAL-CATALYZED OXIDATION; IRON; RETINOPATHY OF PREMATURITY ID METAL-CATALYZED OXIDATION; GLUTAMINE-SYNTHETASE; FREE-RADICALS; CARDIAC RESUSCITATION; REPERFUSION; INJURY; OXYGEN; PROTEINS; CONSEQUENCES; BICARBONATE AB Organ damage can occur quickly when blood flow is compromised. Lactic acidosis has long been associated with such ischemia, and many physicians assume that organ damage is caused by this acidosis. However, reviewing the literature related to hypoxia and ischemia reveals little data to support the concept of acidosis as damaging to tissue. In contrast, recent studies indicate that the acidosis is actually protective, even during reperfusion when cellular damage may occur. Reperfusion is accompanied by generation of free radicals and other reactive species that can damage proteins, membranes, and nucleic acids, supporting an emerging view that implicates these reactive species in the actual tissue damage. The critical targets of the damaging species are not known, but reaction with key enzymes and structural proteins could certainly disrupt organ function. Cellular proteins are oxidatively modified during reperfusion, in part by metal-catalyzed oxidation in which cellular iron plays a key role. Metal-catalyzed oxidation of proteins may be important in the pathogenesis of other disorders, including the potentially blinding disease, retinopathy of the premature. RP LEVINE, RL (reprint author), NHLBI,BIOCHEM LAB,BLDG 3,ROOM 106,BETHESDA,MD 20892, USA. RI Levine, Rodney/D-9885-2011 NR 36 TC 56 Z9 56 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD OCT PY 1993 VL 7 IS 13 BP 1242 EP 1246 PG 5 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA MB376 UT WOS:A1993MB37600007 PM 8405809 ER EF